@article {1748441,
	title = {Epidemiologic Evaluation of Retinopathy of Prematurity Severity in a Large Telemedicine Program in India Using Artificial Intelligence},
	journal = {Ophthalmology},
	volume = {130},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {837-843},
	abstract = {PURPOSE: Epidemiological changes in retinopathy of prematurity (ROP) depend on neonatal care, neonatal mortality, and the ability to carefully titrate and monitor oxygen. We evaluate whether an artificial intelligence (AI) algorithm for assessing ROP severity in babies can be used to evaluate changes in disease epidemiology in babies from South India over a 5-year period. DESIGN: Retrospective cohort study. PARTICIPANTS: Babies (3093) screened for ROP at neonatal care units (NCUs) across the Aravind Eye Care System (AECS) in South India. METHODS: Images and clinical data were collected as part of routine tele-ROP screening at the AECS in India over 2 time periods: August 2015 to October 2017 and March 2019 to December 2020. All babies in the original cohort were matched 1:3 by birthweight (BW) and gestational age (GA) with babies in the later cohort. We compared the proportion of eyes with moderate (type 2) or treatment-requiring (TR) ROP, and an AI-derived ROP vascular severity score (from retinal fundus images) at the initial tele-retinal screening exam for all babies in a district, VSS), in the 2 time periods. MAIN OUTCOME MEASURES: Differences in the proportions of type 2 or worse and TR-ROP cases, and VSS between time periods. RESULTS: Among BW and GA matched babies, the proportion [95\% confidence interval {CI}] of babies with type 2 or worse and TR-ROP decreased from 60.9\% [53.8\%-67.7\%] to 17.1\% [14.0\%-20.5\%] (P \&lt; 0.001) and 16.8\% [11.9\%-22.7\%] to 5.1\% [3.4\%-7.3\%] (P \&lt; 0.001), over the 2 time periods. Similarly, the median [interquartile range] VSS in the population decreased from 2.9 [1.2] to 2.4 [1.8] (P \&lt; 0.001). CONCLUSIONS: In South India, over a 5-year period, the proportion of babies developing moderate to severe ROP has dropped significantly for babies at similar demographic risk, strongly suggesting improvements in primary prevention of ROP. These results suggest that AI-based assessment of ROP severity may be a useful epidemiologic tool to evaluate temporal changes in ROP epidemiology. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Artificial Intelligence, Birth Weight, Gestational Age, Humans, Infant, Infant, Newborn, Neonatal Screening, Retinopathy of Prematurity, Retrospective Studies, Risk Factors, Telemedicine},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.03.026},
	author = {deCampos-Stairiker, Mallory A and Coyner, Aaron S and Gupta, Aditi and Oh, Minn and Shah, Parag K and Subramanian, Prema and Venkatapathy, Narendran and Singh, Praveer and Kalpathy-Cramer, Jayashree and Chiang, Michael F and Chan, R V Paul and Campbell, J Peter}
}
@article {1586171,
	title = {Advances in Neuroscience, Not Devices, Will Determine the Effectiveness of Visual Prostheses},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {168-175},
	abstract = {Background: Innovations in engineering and neuroscience have enabled the development of sophisticated visual prosthetic devices. In clinical trials, these devices have provided visual acuities as high as 20/460, enabled coarse navigation, and even allowed for reading of short words. However, long-term commercial viability arguably rests on attaining even better vision and more definitive improvements in tasks of daily living and quality of life. Purpose: Here we review technological and biological obstacles in the implementation of visual prosthetics. Conclusions: Research in the visual prosthetic field has tackled significant technical challenges, including biocompatibility, signal spread through neural tissue, and inadvertent activation of passing axons; however, significant gaps in knowledge remain in the realm of neuroscience, including the neural code of vision and visual plasticity. We assert that further optimization of prosthetic devices alone will not provide markedly improved visual outcomes without significant advances in our understanding of neuroscience.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1887902},
	author = {Abbasi, Bardia and Rizzo, Joseph F}
}
@article {1445334,
	title = {"For Mass Eye and Ear Special Issue" Adaptive Optics in the Evaluation of Diabetic Retinopathy},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 12},
	pages = {1-9},
	abstract = {Retinal imaging is a fundamental tool for clinical and research efforts in the evaluation and management of diabetic retinopathy. Adaptive optics (AO) is an imaging technique that enables correction of over 90\% of the optical aberrations of an individual eye induced primarily by the tear film, cornea and lens. The two major tasks of any AO system are to measure the optical imperfections of the eye and to then compensate for these aberrations to generate a corrected wavefront of reflected light from the eye. AO scanning laser ophthalmoscopy (AOSLO) provides a theoretical lateral resolution limit of 1.4 μm, allowing the study of microscopic features of the retinal vascular and neural tissue. AOSLO studies have revealed irregularities of the photoreceptor mosaic, vascular loss, and details of vascular lesions in diabetic eyes that may provide new insight into development, regression, and response to therapy of diabetic eye disease.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620794},
	author = {AbdelAl, Omar and Ashraf, Mohammed and Sampani, Konstantina and Sun, Jennifer K}
}
@article {1109756,
	title = {Measuring Forward Light Scatter by the Boston Keratoprosthesis in Various Configurations},
	journal = {Cornea},
	volume = {36},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {732-735},
	abstract = {PURPOSE: Light scatter results in degradation of visual function. An optical bench model was used to identify the origins of scatter in the setting of a Boston keratoprosthesis (KPro). The effect of various modifications in the device design and light-blocking configurations was explored. METHODS: A KPro was mounted on a contact lens holder on a bench, and forward light scatter was recorded with a camera attached to a rotating goniometer arm. Scattered light was recorded at different angles for different KPro modifications, and the point-spread function (PSF) curves were recorded. The area under the curve (AUC) was calculated for each PSF curve. RESULTS: The isolated KPro optical cylinder in a totally blackened holding lens had a tight PSF (AUC = 3.3). Additional blackening of the walls of the KPro stem did not further diminish forward scatter significantly. If the holding lens is made translucent by sandblasting (to simulate an in vivo carrier cornea) and the KPro is inserted without a backplate, forward scatter is substantial (AUC = 11.3). If a standard backplate (with holes) is added, light scatter is considerably reduced regardless of whether the backplate is made of polymethyl methacrylate or titanium (AUC = 5.3 and 4.4, respectively). Addition of an acrylic intraocular lens behind the KPro (the pseudophakic KPro setup) did not increase scatter. CONCLUSIONS: Most of the scattered light in eyes implanted with a KPro originates from the surrounding hazy corneal graft. The standard addition of a backplate reduces light scatter. There was no difference in forward light scatter between the aphakic and the pseudophakic KPro.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001197},
	author = {Abdelaziz, Musa and Dohlman, Claes H and Sayegh, Rony R}
}
@article {1179186,
	title = {Evidence of small-fiber neuropathy (SFN) in two patients with unexplained genital sensory loss and sensory urinary cystopathy},
	journal = {J Neurol Sci},
	volume = {380},
	year = {2017},
	month = {2017 Sep 15},
	pages = {82-84},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2017.07.016},
	author = {AbdelRazek, Mahmoud A and Chwalisz, Bart and Oaklander, Anne Louise and Venna, Nagagopal}
}
@article {1586183,
	title = {Home Monitoring for Glaucoma: Current Applications and Future Directions},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {310-314},
	abstract = {Technological advances provide a number of options for glaucoma monitoring outside the office setting, including home-based tonometry and perimetry. This has the potential to revolutionize management of this chronic disease, improve access to care, and enhance patient engagement. Here, we provide an overview of existing technologies for home-based glaucoma monitoring. We also discuss areas for future research and the potential applications of these technologies to telemedicine, which has been brought to the forefront during the ongoing COVID-19 pandemic.},
	keywords = {Biomedical Technology, Diagnostic Techniques, Ophthalmological, Glaucoma, Humans, Intraocular Pressure, Monitoring, Ambulatory, Ophthalmology, Self Care, Telemedicine, Telemetry, Tomography, Optical Coherence, Tonometry, Ocular, Visual Field Tests},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1896759},
	author = {Aboobakar, Inas F and Friedman, David S}
}
@article {1667708,
	title = {Mitochondrial TXNRD2 and ME3 genetic risk scores are associated with specific primary open-angle glaucoma phenotypes},
	journal = {Ophthalmology},
	year = {2023},
	month = {2023 Feb 20},
	abstract = {PURPOSE: Genetic variants in regions that include the mitochondrial genes TXNRD2 and ME3 are associated with primary open-angle glaucoma (POAG) in genome-wide association studies (GWAS). To assess their clinical impact, we investigated whether TXNRD2 and ME3 genetic risk scores (GRSs) are associated with specific glaucoma phenotypes. DESIGN: Cross-sectional study PARTICIPANTS: 2617 POAG cases and 2634 controls from the NEIGHBORHOOD consortium. METHODS: All POAG-associated single nucleotide polymorphisms (SNPs) in the TXNRD2 and ME3 loci were identified using GWAS data (p\&lt;0.05). Of these, 20 TXNRD2 and 24 ME3 SNPs were selected after adjusting for linkage disequilibrium. The correlation between SNP effect size and gene expression levels was investigated using the Gene-Tissue Expression (GTEx) database. GRSs were constructed for each individual using the unweighted sum of TXNRD2, ME3, and TXNRD2+ME3 combined risk alleles. Age and gender-adjusted odds ratios (ORs) for POAG diagnosis were calculated per decile for each GRS. Additionally, the clinical features of POAG cases in the top 1, 5, and 10\% of each GRS were compared to the bottom 1, 5, and 10\%, respectively. MAIN OUTCOME MEASURES: POAG OR per GRS decile; maximal treated intraocular pressure (IOP) and prevalence of paracentral visual field loss among POAG cases with high vs. low GRSs. RESULTS: Increased SNP effect size strongly correlated with higher TXNRD2 and lower ME3 expression levels (r=0.95 and -0.97, respectively, p\&lt;0.05 for both). Individuals in decile 10 of TXNRD2+ME3 GRS had the highest odds of POAG diagnosis (OR=1.79 compared to decile 1, p\&lt;0.001). POAG cases in the top 1\% of TXNRD2 GRS had higher mean maximal treated IOP compared to the bottom 1\% (19.9 mmHg vs 15.6 mmHg, adjusted p=0.03). POAG cases in the top 1\% of ME3 and TXNRD2+ME3 GRS had a higher prevalence of paracentral field loss compared to the bottom 1\% (72.7-88.9\% vs 14.3-33.3\%; adjusted p=0.03 for both). CONCLUSIONS: POAG patients with higher TXNRD2 and ME3 GRSs had higher treated IOP and a greater prevalence of paracentral field loss. Functional studies exploring how these variants impact mitochondrial function in glaucoma patients are warranted.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.02.018},
	author = {Aboobakar, Inas F and Kinzy, Tyler G and Zhao, Yan and Fan, Bao Jian and Pasquale, Louis R and Qassim, Ayub and Kolovos, Antonia and Schmidt, Joshua M and Craig, Jamie E and Bailey, Jessica N Cooke and Wiggs, Janey L and NEIGHBORHOOD Consortium}
}
@article {1629458,
	title = {The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities-A review},
	journal = {Clin Exp Ophthalmol},
	volume = {50},
	number = {2},
	year = {2022},
	month = {2022 Mar},
	pages = {143-162},
	abstract = {Glaucoma refers to a heterogenous group of disorders characterised by progressive loss of retinal ganglion cells and associated visual field loss. Both early-onset and adult-onset forms of the disease have a strong genetic component. Here, we summarise the known genetic associations for various forms of glaucoma and the possible functional roles for these genes in disease pathogenesis. We also discuss efforts to translate genetic knowledge into clinical practice, including gene-based tests for disease diagnosis and risk-stratification as well as gene-based therapies.},
	issn = {1442-9071},
	doi = {10.1111/ceo.14035},
	author = {Aboobakar, Inas F and Wiggs, Janey L}
}
@article {1698286,
	title = {Rare protective variants and glaucoma-relevant cell stressors modulate Angiopoietin-like 7 expression},
	journal = {Hum Mol Genet},
	volume = {32},
	number = {15},
	year = {2023},
	month = {2023 Jul 20},
	pages = {2523-2531},
	abstract = {Rare missense and nonsense variants in the Angiopoietin-like 7 (ANGPTL7) gene confer protection from primary open-angle glaucoma (POAG), though the functional mechanism remains uncharacterized. Interestingly, a larger variant effect size strongly correlates with in silico predictions of increased protein instability (r = -0.98), suggesting that protective variants lower ANGPTL7 protein levels. Here, we show that missense and nonsense variants cause aggregation of mutant ANGPTL7 protein in the endoplasmic reticulum (ER) and decreased levels of secreted protein in human trabecular meshwork (TM) cells; a lower secreted:intracellular protein ratio strongly correlates with variant effects on intraocular pressure (r = 0.81). Importantly, accumulation of mutant protein in the ER does not increase expression of ER stress proteins in TM cells (P \&gt; 0.05 for all variants tested). Cyclic mechanical stress, a glaucoma-relevant physiologic stressor, also significantly lowers ANGPTL7 expression in primary cultures of human Schlemm{\textquoteright}s canal (SC) cells (-2.4-fold-change, P = 0.01). Collectively, these data suggest that the protective effects of ANGPTL7 variants in POAG stem from lower levels of secreted protein, which may modulate responses to physiologic and pathologic ocular cell stressors. Downregulation of ANGPTL7 expression may therefore serve as a viable preventative and therapeutic strategy for this common, blinding disease.},
	keywords = {Angiopoietin-Like Protein 7, Angiopoietin-like Proteins, Angiopoietins, Glaucoma, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Trabecular Meshwork},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddad083},
	author = {Aboobakar, Inas F and Collantes, Edward Ryan A and Hauser, Michael A and Stamer, W Daniel and Wiggs, Janey L}
}
@article {509156,
	title = {Cellular mechanism of oral absorption of solidified polymer micelles.},
	journal = {Nanomedicine},
	volume = {11},
	number = {8},
	year = {2015},
	month = {2015 Nov},
	pages = {1993-2002},
	abstract = {UNLABELLED: Oral delivery of poorly soluble and permeable drugs represents a significant challenge in drug development. The oral delivery of drugs remains to be the ultimate route of any drugs. However, in many cases, drugs are not absorbed well in the gastrointestinal tract, or they lose their activity. Polymer micelles were recognized as an effective carrier system for drug encapsulation, and are now studied as a vehicle for oral delivery of insoluble compounds. We characterized the properties of monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles, and visualized their internalization in mouse small intestine. Using Caco-2 cells as a cellular model, we studied the kinetics of particle uptake, their transport, and the molecular mechanism of their intestinal absorption. Moreover, by inhibiting specific endocytosis pathways, pharmacologically and genetically, we found that mPEG-PLA nanoparticle endocytosis is mediated by clathrin in an energy-dependent manner, and that the low-density lipoprotein receptor is involved. FROM THE CLINICAL EDITOR: Many current drugs used are non-water soluble and indeed, the ability to deliver these drugs via the gastrointestinal tract remains the holy grail for many researchers. The authors in this paper developed monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles as a drug nanocarrier, and studied the mechanism of uptake across intestinal cells. The findings should improve our current understanding and point to the development of more nanocarriers.},
	issn = {1549-9642},
	doi = {10.1016/j.nano.2015.07.008},
	author = {Abramov, Eva and Cassiola, Flavia and Schwob, Ouri and Karsh-Bluman, Adi and Shapero, Mara and Ellis, James and Luyindula, Dema and Adini, Irit and D{\textquoteright}Amato, Robert J and Benny, Ofra}
}
@article {1549035,
	title = {Autosomal-dominant WFS1-related disorder-Report of a novel WFS1 variant and review of the phenotypic spectrum of autosomal recessive and dominant forms},
	journal = {Am J Med Genet A},
	volume = {185},
	number = {2},
	year = {2021},
	month = {2021 02},
	pages = {528-533},
	abstract = {Wolfram syndrome was initially reported as an autosomal recessive (AR), progressive neurodegenerative disorder that leads to diabetes insipidus, childhood onset diabetes mellitus (DM), optic atrophy, and deafness (D) also known as DIDMOAD. However, heterozygous dominant pathogenic variants in Wolfram syndrome type 1 (WFS1) may lead to distinct, allelic conditions, described as isolated sensorineural hearing loss (SNHL), syndromic SNHL, congenital cataracts, or early onset DM. We report a family with a novel dominant, likely pathogenic variant in WFS1 (NM_006005.3) c.2605_2616del12 (p.Ser869_His872del), resulting in cataracts, SNHL, and DM in a female and her mother. A maternal aunt had cataracts, DM, and SNHL but was not tested for the familial WFS1 mutation. Both the mother and maternal aunt had early menopause by age 43 years and infertility which may be a coincidental finding that has not been associated with autosomal dominant AD WFS1-related disorder to the best of our knowledge. Screening at risk individuals in families with the AR Wolfram syndrome, for DM, SNHL, and for cataracts is indicated.},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.61945},
	author = {Abu-El-Haija, Aya and McGowan, Caroline and Vanderveen, Deborah and Bodamer, Olaf}
}
@article {692331,
	title = {A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease.},
	journal = {Ophthalmology},
	volume = {123},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {1449-57},
	abstract = {PURPOSE: To evaluate the safety and efficacy of topical tacrolimus 0.05\% versus topical methylprednisolone 0.5\% in patients with ocular graft-versus-host disease (GVHD). DESIGN: Phase 1/2 prospective, randomized, double-masked clinical trial. PARTICIPANTS: Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled. METHODS: Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05\% and 16 patients were treated with topical methylprednisolone 0.5\% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen. MAIN OUTCOME MEASURES: Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). RESULTS: After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P\&nbsp;= 0.06). However, burning sensation was more pronounced with tacrolimus (P\&nbsp;= 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55\% vs. 23\% reduction, respectively; P\&nbsp;= 0.01) and achieved significant improvement in TBUT when compared with baseline (P \&lt; 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27\% reduction; P\&nbsp;= 0.02), but was marginal with methylprednisolone (32\% reduction; P\&nbsp;= 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P\&nbsp;= 0.003; methylprednisolone, P\&nbsp;= 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group (P\&nbsp;= 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P\&nbsp;= 0.04). CONCLUSIONS: Topical tacrolimus 0.05\% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.02.044},
	author = {Abud, Tulio B and Amparo, Francisco and Saboo, Ujwala S and Di Zazzo, Antonio and Dohlman, Thomas H and Ciolino, Joseph B and Hamrah, Pedram and Dana, Reza}
}
@article {630206,
	title = {Current Treatment Modalities of JIA-associated Uveitis and its Complications: Literature Review.},
	journal = {Ocul Immunol Inflamm},
	volume = {24},
	number = {4},
	year = {2016},
	month = {2016 Aug},
	pages = {431-9},
	abstract = {Uveitis is a common and serious complication of juvenile idiopathic arthritis. Up to 75\% of all cases of anterior uveitis in childhood are associated with juvenile idiopathic arthritis. Despite the remarkable progress in early detection and treatment of inflammation, vision-threatening complications of uveitis still occur in almost 60\% of patients. Structural complications include band keratopathy, maculopathy (macular edema, macular cysts, and epiretinal membrane), glaucomatous optic neuropathy, and cataracts. The management of complications in juvenile idiopathic arthritis is usually complex and requires early surgical intervention. In this paper, we review the general concepts of common ocular complications seen in patients with JIA-associated uveitis, with special attention to the recent diagnostic and preferred treatment approaches at the Massachusetts Eye Research and Surgery Institution. Received 9 March 2015; revised 30 September 2015; accepted 30 October 2015; published online 14 January 2016.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2015.1115878},
	author = {Abusamra, Khawla and Maghsoudlou, Armin and Roohipoor, Ramak and Valdes-Navarro, Manuel and Lee, Stacey and Foster, C Stephen}
}
@article {836756,
	title = {Intraocular Lymphoma: Descriptive Data of 26 Patients Including Clinico-pathologic Features, Vitreous Findings, and Treatment Outcomes.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Jul 20},
	pages = {1-6},
	abstract = {PURPOSE: To describe clinical manifestations, diagnostic approaches, therapy, and outcomes of biopsy-proven intraocular lymphoma. METHODS: Review of tertiary referral center records between 2005 and 2015. RESULTS: A total of 51 eyes of 26 patients were included; mean age of onset was 60.42 years. Common ocular complaints included floaters (42\%) and blurred vision (35\%); 62\% of patients had ocular and central nervous system involvement; 11\% had systemic lymphoma; and 27\% had only ocular involvement. Vitreous analysis was positive for malignant cells in 77\% of patients on initial biopsy, and in 100\% of patients on repeat biopsy. In total, 20/26 patients received systemic and topical treatment before IOL diagnosis was made; 25 patients received intravitreal methotrexate and/or rituximab; one patient received intracameral rituximab. All patients achieved remission by their final visit. CONCLUSIONS: Intraocular lymphoma often masquerades as intraocular inflammation, resulting in delayed or misdiagnosis with subsequent inappropriate management. Optimal therapy is a challenge for oncologists and ophthalmologists.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2016.1193206},
	author = {Abusamra, Khawla and Oray, Merih and Ebrahimiadib, Nazanin and Lee, Stacey and Anesi, Stephen and Foster, C Stephen}
}
@article {1452957,
	title = {Galectin-3 initiates epithelial-stromal paracrine signaling to shape the proteolytic microenvironment during corneal repair},
	journal = {Sci Signal},
	volume = {12},
	number = {590},
	year = {2019},
	month = {2019 Jul 16},
	abstract = {Paracrine interactions between epithelial cells and stromal fibroblasts occur during tissue repair, development, and cancer. Crucial to these processes is the production of matrix metalloproteinases (MMPs) that modify the microenvironment. Here, we demonstrated that the carbohydrate-binding protein galectin-3 stimulated microenvironment remodeling in the cornea by promoting the paracrine action of secreted interleukin-1β (IL-1β). Through live cell imaging in vitro, we observed rapid activation of the promoter in clusters of cultured human epithelial cells after direct heterotypic contact with single primary human fibroblasts. Soluble recombinant galectin-3 and endogenous galectin-3 of epithelial origin both stimulated MMP9 activity through the induction of IL-1β secretion by fibroblasts. In vivo, mechanical disruption of the basement membrane in wounded corneas prompted an increase in the abundance of IL-1β in the stroma and increased the amount of gelatinase activity in the epithelium. Moreover, corneas of galectin-3-deficient mice failed to stimulate IL-1β after wounding. This mechanism of paracrine control has broad importance for our understanding of how the proteolytic microenvironment is modified in epithelial-stromal interactions.},
	issn = {1937-9145},
	doi = {10.1126/scisignal.aaw7095},
	author = {AbuSamra, Dina B and Mauris, J{\'e}r{\^o}me and Arg{\"u}eso, Pablo}
}
@article {688601,
	title = {A case of bilateral uveitis and papillitis in a patient treated with pembrolizumab.},
	journal = {Eur J Ophthalmol},
	volume = {26},
	number = {3},
	year = {2016},
	month = {2016},
	pages = {e46-8},
	abstract = {PURPOSE: Drug-induced uveitis is a well-known effect of ocular inflammation that has been reported with many medications. Pembrolizumab is a newer generation of the anti-programmed cell death-1 monoclonal antibodies that was recently approved by the Food and Drug Administration for the treatment of advanced melanoma. Immune-mediated adverse events involving different organs have been reported in recent literature in association with this drug. We present the first reported case of uveitis in association with pembrolizumab therapy. CASE REPORT: An 82-year-old man with stage IV melanoma was started on pembrolizumab infusion treatment every 3 weeks. Two months after initiating therapy, he presented with bilateral severe anterior uveitis and papillitis with fast and complete recovery after withholding further pembrolizumab infusions and treatment with topical steroid. Uveitis recurred after restarting pembrolizumab therapy. CONCLUSIONS: In current clinical practice, many new drugs are being approved, requiring better characterization of the prevalence, onset, and nature of adverse events in order to aid development of effective management strategies. Ophthalmologists should keep in mind that drugs are always a possible cause of ocular inflammation in patients presenting with uveitis.},
	issn = {1724-6016},
	doi = {10.5301/ejo.5000724},
	author = {Abusamra, Khawla and Valdes-Navarro, Manuel and Lee, Stacey and Swan, Robert and Foster, C Stephen and Anesi, Stephen D}
}
@article {1347422,
	title = {Lectin-Glycan Interactions in Corneal Infection and Inflammation},
	journal = {Front Immunol},
	volume = {9},
	year = {2018},
	month = {2018},
	pages = {2338},
	abstract = {The cornea is an extraordinary component of vision that functions as the principal barrier to pathogens in the eye while allowing light transmission into the retina. Understanding the cellular and molecular mechanisms that maintain homeostasis in this tissue is the subject of intense scientific study given the high prevalence of corneal disease. Over the past decade, the interactions between lectins and glycans on plasma membranes have emerged as important regulatory factors in corneal biology. In particular, members of the galectin family have been shown to bind multiple β-galactoside-containing receptors to regulate immunopathological processes associated with viral and bacterial infection, transplantation, wound healing, dry eye, angiogenesis, and lymphangiogenesis. In this review, we describe the current understanding of how these surface interactions intersect with different pathways to activate unique cellular responses in cornea as well as their potential therapeutic implications.},
	issn = {1664-3224},
	doi = {10.3389/fimmu.2018.02338},
	author = {AbuSamra, Dina B and Arg{\"u}eso, Pablo}
}
@article {1732531,
	title = {Preventing development of post-stroke hyperexcitability by optogenetic or pharmacological stimulation of cortical excitatory activity},
	journal = {Neurobiol Dis},
	volume = {184},
	year = {2023},
	month = {2023 Aug},
	pages = {106233},
	abstract = {Stroke is the most common cause of acquired epilepsy, but treatment for preventing the development of post-stroke epilepsy is still unavailable. Since stroke results in neuronal damage and death as well as initial loss of activity in the affected brain region, homeostatic plasticity may be trigged and contribute to an increase in network hyperexcitability that underlies epileptogenesis. Correspondingly, enhancing brain activity may inhibit hyperexcitability from enhanced homeostatic plasticity and prevent post-stroke epileptogenesis. To test these hypotheses, we first used in vivo two-photon and mesoscopic imaging of activity of cortical pyramidal neurons in Thy1-GCaMP6 transgenic mice to determine longitudinal changes in excitatory activity after a photothrombotic ischemic stroke. At 3-days post-stroke, there was a significant loss of neuronal activity in the peri-injury area as indicated by reductions in the frequency of calcium spikes and percentage of active neurons, which recovered to baseline level at day 7, supporting a homeostatic activity regulation of the surviving neurons in the peri-injury area. We further used optogenetic stimulation to specifically stimulate activity of pyramidal neurons in the peri-injury area of Thy-1 channelrhodopsin transgenic mice from day 5 to day 15 after stroke. Using pentylenetetrazole test to evaluate seizure susceptibility, we showed that stroke mice are more susceptible to Racine stage V seizures (time latency 54.3\&nbsp;{\textpm}\&nbsp;12.9\&nbsp;min) compared to sham mice (107.1\&nbsp;{\textpm}\&nbsp;13.6\&nbsp;min), but optogenetic stimulation reversed the increase in seizure susceptibility (114.0\&nbsp;{\textpm}\&nbsp;9.2\&nbsp;min) in mice with stroke. Similarly, administration of D-cycloserine, a partial N-methyl-d-aspartate (NMDA) receptor agonist that can mildly enhance neuronal activity without causing post-stroke seizure, from day 5 to day 15 after a stroke significantly reversed the increase in seizure susceptibility. The treatment also resulted in an increased survival of glutamic acid decarboxylase 67 (GAD67) positive interneurons and a reduced activation of glial fibrillary acidic protein (GFAP) positive reactive astrocytes. Thus, this study supports the involvement of homeostatic activity regulation in the development of post-stroke hyperexcitability and potential application of activity enhancement as a novel strategy to prevent post-stroke late-onset seizure and epilepsy through regulating cortical homeostatic plasticity.},
	keywords = {Animals, Epilepsy, Mice, Mice, Transgenic, Optogenetics, Seizures, Stroke},
	issn = {1095-953X},
	doi = {10.1016/j.nbd.2023.106233},
	author = {Adhikari, Yadav and Ma, Cun-Gen and Chai, Zhi and Jin, Xiaoming}
}
@article {1402571,
	title = {Meibomian Gland Morphology Is a Sensitive Early Indicator of Meibomian Gland Dysfunction},
	journal = {Am J Ophthalmol},
	volume = {200},
	year = {2019},
	month = {2019 Apr},
	pages = {16-25},
	abstract = {PURPOSE: To investigate the relationship between meibomian gland (MG) morphology and clinical dry eye tests in patients with meibomian gland dysfunction (MGD). DESIGN: Cross-sectional study. SUBJECTS: Total 538 MGD patients and 21 healthy controls. METHODS: MG loss on meibography images of upper (UL) and lower lids (LL) was graded on a scale of 0 (lowest degree of MG loss) to 3. MG length, thickness, and interglandular space in the UL were measured. Clinical tests included meibum expression and quality, tear film break-up time, ocular staining, osmolarity, Schirmer I, blink interval timing, and Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: Mean UL and LL meibogrades were significantly higher in MGD patients compared to controls (P\&nbsp;\&lt; .001 for UL and LL). The sensitivity and specificity of the meibograde as a diagnostic parameter for MGD was 96.7\% and 85\%, respectively. Schirmer I was significantly increased in MGD patients with meibograde 1 compared to patients with meibograde 0, 2, and 3 in the UL (P \&lt; .05). MG thickness increased with higher meibograde (P \&lt; .001). MG morphology correlated significantly but weakly with several clinical parameters (P \&lt; .05). OSDI did not correlate with any MG morphologic parameter. CONCLUSIONS: Grading of MG loss using meibograde effectively diagnoses MGD. Compensatory mechanisms such as increased aqueous tear production and dilation of MGs make early detection of MGD difficult by standard clinical measures of dry eye, whereas morphologic analysis of MGs reveals an early stage of MGD, and therefore represents a complementary clinical parameter with diagnostic potential.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.12.006},
	author = {Adil, Muhammed Yasin and Xiao, Jiaxin and Olafsson, Jonatan and Chen, Xiangjun and Lagali, Neil S and R{\ae}der, Sten and Utheim, {\O}ygunn A and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1059746,
	title = {A novel strategy to enhance angiogenesis in vivo using the small VEGF-binding peptide PR1P},
	journal = {Angiogenesis},
	volume = {20},
	number = {3},
	year = {2017},
	month = {2017 Aug},
	pages = {399-408},
	abstract = {Therapeutic angiogenesis is an experimental frontier in vascular biology that seeks to deliver angiogenic growth factors to ischemic or injured tissues to promote targeted formation of new blood vessels as an alternative approach to surgical revascularization procedures. Vascular endothelial growth factor (VEGF) is a potent angiogenic signal protein that is locally upregulated at sites of tissue injury. However, therapies aimed at increasing VEGF levels experimentally by injecting VEGF gene or protein failed to improve outcomes in human trials in part due to its short half-life and systemic toxicity. We recently designed a novel 12-amino acid peptide (PR1P) whose sequence was derived from an extracellular VEGF-binding domain of the pro-angiogenic glycoprotein prominin-1. In this study, we characterized the molecular binding properties of this novel potential therapeutic for targeted angiogenesis and provided the foundation for its use as an angiogenic molecule that can potentiate endogenous VEGF. We showed that PR1P bound VEGF directly and enhanced VEGF binding to endothelial cells and to VEGF receptors VEGFR2 and neuropilin-1. PR1P increased angiogenesis in the murine corneal micropocket assay when combined with VEGF, but had no activity without added VEGF. In addition, PR1P also enhanced angiogenesis in murine choroidal neovascularization and wound-healing models and augmented reperfusion in a murine hind-limb ischemia model. Together our data suggest that PR1P enhanced angiogenesis by potentiating the activity of endogenous VEGF. In so doing, this novel therapy takes advantage of endogenous VEGF gradients generated in injured tissues and may improve the efficacy of and avoid systemic toxicity seen with previous VEGF therapies.},
	issn = {1573-7209},
	doi = {10.1007/s10456-017-9556-7},
	author = {Adini, Avner and Adini, Irit and Chi, Zai-Long and Derda, Ratmir and Birsner, Amy E and Matthews, Benjamin D and D{\textquoteright}Amato, Robert J}
}
@article {1661840,
	title = {Association of Neighborhood Child Opportunity Index with presenting visual acuity in amblyopic children},
	journal = {J AAPOS},
	volume = {27},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {20.e1-20.e5},
	abstract = {PURPOSE: To demonstrate the use of a novel measure of neighborhood quality, the Child Opportunity Index (COI), for investigating health disparities in pediatric ophthalmology. METHODS: This study included children 2-12 years of age from a registry of patients diagnosed with amblyopia at an urban pediatric hospital between 2010 and 2014. Children previously treated for amblyopia were excluded. Patient demographics, residential addresses, and logMAR visual acuities were collected. The association between visual acuity at presentation and COI was examined using linear mixed-effects models adjusting for individual-level factors, including age, sex, race, ethnicity, and insurance type. RESULTS: This study included 1,050 amblyopic children, of whom 317 (37\%) were non-White and 149 (19\%) were Hispanic; 461 (44\%) had public insurance. Regarding residence, 129 (12\%) lived in areas of very low opportunity (COI \&lt;20); 489 (47\%) in areas of very high opportunity (COI >=80). Children residing in the lowest opportunity neighborhoods correctly identified approximately two fewer letters at presentation with their better-seeing eye compared with children from the highest opportunity neighborhoods after adjusting for individual-level factors (-0.0090 logMAR per 20 unit increase in COI; 95\% CI, -0.0172 to -0.0008; P = 0.031). No difference was appreciated in the worse-seeing eye. CONCLUSIONS: Amblyopic children residing in communities with low neighborhood opportunity had slightly worse visual acuity in the better-seeing eye at presentation. Although statistically significant in the better-seeing eye, the two-letter difference attributable to neighborhood environment may not be clinically significant, and the impact of this disparity on treatment outcomes deserves further investigation.},
	keywords = {Amblyopia, Child, Humans, Treatment Outcome, Visual Acuity},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.11.013},
	author = {Adomfeh, Jean and Chinn, Ryan N and Michalak, Suzanne M and Shoshany, Talia N and Bishop, Kaila and Hunter, David G and Jastrzembski, Benjamin G and Oke, Isdin}
}
@article {1653585,
	title = {Association of Race, Ethnicity, and Socioeconomic Status With Visual Impairment in Adolescent Children in the US},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {10},
	year = {2022},
	month = {2022 Oct 01},
	pages = {1006-1010},
	abstract = {Importance: Although racial, ethnic, and socioeconomic disparities in visual impairment have been described in adults, few studies have focused on the adolescent population, which may provide insight into the emergence of vision health inequities. Objective: To describe visual health disparities among adolescent children in the US. Design, Setting, and Participants: This was a cross-sectional study of adolescents from the 2005 to 2008 National Health and Nutrition Examination Survey. Participants were aged 12 to 18 years with a completed visual function questionnaire and eye examination. Data analyses were conducted from January 19 to July 20, 2022. Main Outcomes and Measures: Outcomes included subjective (self-reported poor vision) and objective (visual acuity worse than 20/40 in the better-seeing eye) measures of visual function. Multivariable logistic and linear regression analyses were conducted to examine the association between the sociodemographic risk factors and each outcome, adjusting for age, sex, and other covariates. Results: The 2833 included participants (mean [SD] age, 15.5 [2.0] years; 1407 female participants [49\%]) represent a survey-weighted 57 million US adolescent children, of whom 14\% were non-Hispanic Black participants (876), 11\% were Mexican American participants (828), 63\% were non-Hispanic White participants (816), and 11\% were other race and ethnicity (313). A total of 5\% of participants (266) were not US citizens, and 19\% (773) had a family income below the poverty threshold. There were increased odds of self-reported poor vision among Black (odds ratio [OR], 2.85; 95\% CI, 2.00-4.05; P \&lt; .001), Mexican American (OR, 2.83; 95\% CI, 1.70-4.73; P \&lt; .001), and low-income (OR, 2.44; 95\% CI, 1.63-3.65; P \&lt; .001) adolescent children. Similarly, there were increased odds of visual acuity worse than 20/40 in the better-seeing eye among Black (OR, 2.13; 95\% CI, 1.41-3.24; P = .001), Mexican American (OR, 2.13; 95\% CI, 1.39-3.26; P = .001), and non-US citizen (OR, 1.96; 95\% CI, 1.10-3.49; P = .02) participants. Conclusions and Relevance: In this nationally representative sample from 2005 to 2008, adolescent children identifying as Black, Mexican American, low-income, or non-US citizen were more likely to report poor subjective visual function and perform worse on objective visual acuity testing. A greater understanding of the underlying etiology of these disparities may yield opportunities for improving vision at the population level.},
	keywords = {Adolescent, Adult, Child, Cross-Sectional Studies, ethnicity, Female, Humans, Nutrition Surveys, Social Class, United States, Vision Disorders, Vision, Low},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.3627},
	author = {Adomfeh, Jean and Jastrzembski, Benjamin G and Oke, Isdin}
}
@article {1814376,
	title = {QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration},
	journal = {Nat Commun},
	volume = {15},
	number = {1},
	year = {2024},
	month = {2024 Mar 04},
	pages = {1972},
	abstract = {DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and \&gt;8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.},
	keywords = {DNA Methylation, Epigenesis, Genetic, Epigenome, Humans, Macular Degeneration, Retina},
	issn = {2041-1723},
	doi = {10.1038/s41467-024-46063-8},
	author = {Advani, Jayshree and Mehta, Puja A and Hamel, Andrew R and Mehrotra, Sudeep and Kiel, Christina and Strunz, Tobias and Corso-D{\'\i}az, Ximena and Kwicklis, Madeline and van Asten, Freekje and Ratnapriya, Rinki and Chew, Emily Y and Hernandez, Dena G and Montezuma, Sandra R and Ferrington, Deborah A and Weber, Bernhard H F and Segr{\`e}, Ayellet V and Swaroop, Anand}
}
@article {630236,
	title = {Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac.},
	journal = {Am J Surg Pathol},
	volume = {40},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {519-28},
	abstract = {High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30\% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7\% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89\% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5\%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12.5\%) was predominantly keratinizing. The presence of HR-HPV in 30\% of OSSNs and at least 66.7\% of LSSCCs suggests the possibility of an etiologic role for HR-HPV at these sites.},
	issn = {1532-0979},
	doi = {10.1097/PAS.0000000000000581},
	author = {Afrogheh, Amir H and Jakobiec, Frederick A and Hammon, Rebecca and Grossniklaus, Hans E and Rocco, James and Lindeman, Neal I and Sadow, Peter M and Faquin, William C}
}
@article {1598054,
	title = {Femtosecond Laser Assisted Cataract Surgery: A Review},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {8},
	year = {2021},
	month = {2021 Nov 17},
	pages = {618-627},
	abstract = {Femtosecond laser assisted cataract surgery (FLACS) offers a level of precision, accuracy and customization that is not possible with manual phacoemulsification (MP). With the increase of patient expectations and premium intraocular lens utilization in the era of refractive cataract surgery, predictability and accuracy has become of utmost importance. FLACS has four main functions: creation of a consistently sized round capsulotomy, treatment of keratometric astigmatism with arcuate incisions, construction of clear corneal incisions, and fragmentation and/or softening of the lens. However, FLACS may have limitations due to suction loss, incomplete capsulotomy or poor pupillary dilation. Patient selection and surgeon experience is critical. This review article will focus on the various platforms available for FLACS, the steps in cataract surgery it can perform, and overall advantages and limitations of the technology.},
	keywords = {Cataract, Cataract Extraction, Humans, Laser Therapy, Lasers, Phacoemulsification},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1890792},
	author = {Agarwal, Kanika and Hatch, Kathryn}
}
@article {1517211,
	title = {Twenty-four Month Outcomes in the Collaborative Ocular Tuberculosis Study (COTS)-1: Defining the "Cure" in Ocular Tuberculosis},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Jun 26},
	pages = {1-9},
	abstract = {PURPOSE: To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24\&nbsp;months in the Collaborative Ocular Tuberculosis Study (COTS)-1. METHODS: Of the 945 subjects included in COTS-1, those who completed a 24-month follow-up after completion of treatment were included. The main outcome measure was a number of patients with treatment failure (TF). RESULTS: 228 subjects (120 males; mean age of 42.82\&nbsp;{\textpm}\&nbsp;14.73\&nbsp;years) were included. Most common phenotype of uveitis was posterior ( =\&nbsp;81; 35.53\%), and panuveitis ( =\&nbsp;76; 33.33\%). Fifty-two patients (22.81\%) had TF. On univariable analysis, odds of high TF was observed with bilaterality (OR: 3.46, =\&nbsp;.003), vitreous haze (OR: 2.14, =\&nbsp;.018), and use of immunosuppressive therapies (OR: 5.45, =\&nbsp;.003). However, only bilaterality was significant in the multiple regression model (OR: 2.84; =\&nbsp;.02). CONCLUSIONS: Majority of subjects (\&gt;75\%) achieved cure in the COTS-1 at 24-month follow-up. The concept of "cure" may be a valuable clinical endpoint in trials for OTB.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1761401},
	author = {Agarwal, Aniruddha and Agrawal, Rupesh and Raje, Dhananjay and Testi, Ilaria and Mahajan, Sarakshi and Gunasekeran, Dinesh Visva and Aggarwal, Kanika and Murthy, Somasheila I and Westcott, Mark and Chee, Soon-Phaik and McCluskey, Peter and Ho, Su Ling and Teoh, Stephen and Cimino, Luca and Biswas, Jyotirmay and Narain, Shishir and Agarwal, Manisha and Mahendradas, Padmamalini and Khairallah, Moncef and Jones, Nicholas and Tugal-Tutkun, Ilknur and Babu, Kalpana and Basu, Soumayava and Carre{\~n}o, Ester and Lee, Richard and Al-Dhibi, Hassan and Bodaghi, Bahram and Invernizzi, Alessandro and Goldstein, Debra A and Herbort, Carl P and Barisani-Asenbauer, Talin and Gonz{\'a}lez-L{\'o}pez, Julio J and Androudi, Sofia and Bansal, Reema and Moharana, Bruttendu and Esposti, Simona Degli and Tasiopoulou, Anastasia and Nadarajah, Sengal and Agarwal, Mamta and Abraham, Sharanaya and Vala, Ruchi and Singh, Ramandeep and Sharma, Aman and Sharma, Kusum and Zierhut, Manfred and Kon, Onn Min and Cunningham, Emmett T and Kempen, John H and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali}
}
@article {1698271,
	title = {Stepwise approach for fundus imaging in the diagnosis and management of posterior uveitis},
	journal = {Surv Ophthalmol},
	volume = {68},
	number = {3},
	year = {2023},
	month = {2023 May-Jun},
	pages = {446-480},
	abstract = {An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for the diagnosis and management of inflammatory disorders such as uveitis. The recent technological breakthroughs have led to the development of imaging platforms that can evaluate the layers of retina and choroid and the structural and functional alteration in these tissues. Ophthalmologists heavily rely on imaging modalities such as dye-based angiographies (fluorescein angiography and indocyanine green angiography), optical coherence tomography, fundus autofluorescence, as well as dye-less angiography such as optical coherence tomography angiograph,y for establishing a precise diagnosis and understanding the pathophysiology of the diseases. Furthermore, these tools are now being deployed with a {\textquoteright}multimodal{\textquoteright} approach for swift and accurate diagnosis. In this comprehensive review, we outline the imaging platforms used for evaluation of posterior uveitis and discuss the organized, algorithmic approach for the assessment of the disorders. Additionally, we provide an insight into disease-specific characteristic pathological changes and the established strategies to rule out disorders with overlapping features on imaging.},
	keywords = {Choroid, Fluorescein Angiography, Fundus Oculi, Humans, Multimodal Imaging, Tomography, Optical Coherence, Uveitis, Uveitis, Posterior},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2023.01.006},
	author = {Agarwal, Aniruddha and Pichi, Francesco and Invernizzi, Alessandro and Grewal, Dilraj S and Singh, Rohan Bir and Upadhyay, Awaneesh}
}
@article {1653578,
	title = {Quantitative Analysis of the Choroidal Vascularity in Eyes with Uveitis Using Optical Coherence Tomography Angiography: A Systematic Review},
	journal = {Ocul Immunol Inflamm},
	volume = {31},
	number = {9},
	year = {2023},
	month = {2023 Nov},
	pages = {1792-1803},
	abstract = {PURPOSE: The purpose of this systematic review is to identify techniques used for quantification of choriocapillaris (CC) flow in eyes with uveitis using optical coherence tomography angiography (OCTA), report reliability and level of correlation with techniques such as indocyanine green angiography (ICGA). METHODS: A systematic search of several databases was done. The studies were analyzed for techniques of measurement, reliability, and correlation with other modalities. Risk of bias assessment was performed. RESULTS: Thirteen studies were included. CC vessel density (7 studies) and flow deficit area (4 studies) were the most used indices. There was significant heterogeneity in the studies due to differences in the scan protocol, thresholding strategy, and analysis. Comparison with ICGA was performed by only one study, and reliability indices were reported by only two studies. CONCLUSION: OCTA is a useful tool to measure the CC vascularity in eyes with uveitis. However, standardized acquisition and analysis protocols are needed.},
	keywords = {Choroid, Fluorescein Angiography, Humans, Indocyanine Green, Reproducibility of Results, Tomography, Optical Coherence, Uveitis},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2115929},
	author = {Agarwal, Aniruddha and Singh, Rohan Bir and Erckens, Roel J and Berendschot, Tos T J M and Webers, Carroll A B}
}
@article {1333845,
	title = {An update on inflammatory choroidal neovascularization: epidemiology, multimodal imaging, and management},
	journal = {J Ophthalmic Inflamm Infect},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Sep 12},
	pages = {13},
	abstract = {Inflammatory choroidal neovascular membranes are challenging to diagnose and manage. A number of uveitic entities may be complicated by the development of choroidal neovascularization leading to a decrease in central visual acuity. In conditions such as punctate inner choroidopathy, development of choroidal neovascularization is extremely common and must be suspected in all cases. On the other hand, in patients with conditions such as serpiginous choroiditis, and multifocal choroiditis, it may be difficult to differentiate between inflammatory choroiditis lesions and choroidal neovascularization. Multimodal imaging analysis, including the recently introduced technology of optical coherence tomography angiography, greatly aid in the diagnosis and management of inflammatory choroidal neovascularization. Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy.},
	issn = {1869-5760},
	doi = {10.1186/s12348-018-0155-6},
	author = {Agarwal, Aniruddha and Invernizzi, Alessandro and Singh, Rohan Bir and Foulsham, William and Aggarwal, Kanika and Handa, Sabia and Agrawal, Rupesh and Pavesio, Carlos and Gupta, Vishali}
}
@article {1351127,
	title = {Treatment of pseudodendrites in herpes zoster ophthalmicus with topical ganciclovir 0.15\% gel},
	journal = {Cornea},
	volume = {33},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {109-13},
	abstract = {PURPOSE: There is no standard of treatment for epithelial pseudodendrites in herpes zoster ophthalmicus (HZO). The purpose of this study is to report the topical antiviral drug, 0.15\% ganciclovir for treatment of these lesions. METHODS: This is a retrospective, interventional case series of 4 patients who were diagnosed with HZO epithelial pseudodendrites despite being given oral antiviral treatment and who underwent 0.15\% ganciclovir gel topical treatment. Main outcome measures included epithelial healing time, visual acuity, and corneal sensation. RESULTS: All 4 patients were immunocompetent and had epithelial lesions unresponsive to antiviral treatment with oral valacyclovir. Treatment with topical 0.15\% ganciclovir gel 5 times a day resulted in the lesions healing successfully within 7 days with improved visual acuity in 3 patients and an increase in corneal sensation in 2 of the 4 patients. CONCLUSIONS: Topical 0.15\% ganciclovir gel, 5 times a day until pseudodendritic lesion healing and tapering to bid for 2 to 4 weeks thereafter, is an effective treatment for pseudodendrites in HZO-affected cases that are often a challenge to manage with other oral or topical antivirals.},
	keywords = {Administration, Topical, Aged, Antiviral Agents, Female, Ganciclovir, Herpes Zoster Ophthalmicus, Humans, Keratitis, Dendritic, Male, Middle Aged, Ophthalmic Solutions, Retrospective Studies, Treatment Outcome, Visual Acuity},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000020},
	author = {Aggarwal, Shruti and Cavalcanti, Bernardo M and Pavan-Langston, Deborah}
}
@article {504081,
	title = {Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with InVivo Confocal Microscopy.},
	journal = {Ocul Surf},
	volume = {13},
	number = {3},
	year = {2015},
	month = {2015 Jul},
	pages = {250-62},
	abstract = {OBJECTIVE: Patients suffering from corneal neuropathy may present with photoallodynia; i.e., increased light sensitivity, frequently with a normal slit-lamp examination. This study aimed to evaluate the efficacy of autologous serum tears (AST) for treatment of severe photoallodynia in corneal neuropathy and to correlate clinical findings with corneal subbasal nerve alterations by in\&nbsp;vivo confocal microscopy (IVCM). METHODS: Retrospective case control study with 16 patients with neuropathy-induced severe photoallodynia compared to 16 normal controls. Symptom severity, clinical examination and bilateral corneal IVCM scans were recorded. RESULTS: All patients suffered from extreme photoallodynia (8.8{\textpm}1.1) with no concurrent ocular surface disease. Subbasal nerves were significantly decreased at baseline in patients compared to controls; total nerve length (9208{\textpm}1264 vs 24714{\textpm}1056 μm/mm(2); P\&lt;.0001) and total nerve number (9.6{\textpm}1.4 vs 28.6{\textpm}2.0; P\&lt;.0001), respectively. Morphologically, significantly increased reflectivity (2.9{\textpm}0.2 vs 1.8{\textpm}0.1; P\&lt;.0001), beading (in 93.7\%), and neuromas (in 62.5\%) were seen. AST (3.6{\textpm}2.1 months) resulted in significantly decreased symptom severity (1.6{\textpm}1.7; P=.02). IVCM demonstrated significantly improved nerve parameters (P\&lt;.005), total nerve length (15451{\textpm}1595 μm/mm(2)), number (13.9{\textpm}2.1), and reflectivity (1.9{\textpm}0.1). Beading and neuromas were seen in only 56.2\% and 7.6\% of patients. CONCLUSION: Patients with corneal neuropathy-induced photoallodynia show profound alterations in corneal nerves. AST restores nerve topography through nerve regeneration, and this correlated with improvement in patient-reported photoallodynia. The data support the notion that corneal nerve damage results in alterations in afferent trigeminal pathways to produce photoallodynia.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2015.01.005},
	author = {Aggarwal, Shruti and Kheirkhah, Ahmad and Cavalcanti, Bernardo M and Cruzat, Andrea and Colon, Clara and Brown, Emma and Borsook, David and Pr{\"u}ss, Harald and Hamrah, Pedram}
}
@article {1333846,
	title = {In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs{\textquoteright} Endothelial Corneal Dystrophy},
	journal = {Am J Ophthalmol},
	volume = {196},
	year = {2018},
	month = {2018 Dec},
	pages = {136-144},
	abstract = {PURPOSE: To evaluate corneal nerve and immune cell alterations in Fuchs{\textquoteright} endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in\&nbsp;vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss. DESIGN: Prospective, cross-sectional, controlled study. METHODS: Thirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into early (without edema) and late stage (with edema). Corneal IVCM and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC) alterations were evaluated and correlated to clinical parameters. RESULTS: FECD and PBK eyes showed significantly (P\&nbsp;= .001) diminished total nerve length (11.5 {\textpm} 1.3 and 2.9 {\textpm} 0.7\&nbsp;mm/mm) and number (8.8 {\textpm} 1.1 and 2.2\&nbsp;{\textpm} 0.4 n/frame), compared to controls (23.3 {\textpm} 8.1\&nbsp;mm/mm and 25.9 {\textpm} 1.3 n/frame). Decreased nerves corresponded to diminished sensation in FECD (4.9 {\textpm} 0.2\&nbsp;cm; R\&nbsp;= 0.32; P\&nbsp;= .045), compared to controls (5.9 {\textpm} 0.04\&nbsp;cm). Early- and late-stage FECD showed significantly reduced total nerve length (13.1 {\textpm} 1.4 and 9.9 {\textpm} 1.2\&nbsp;mm/mm, respectively) and number (8.2 {\textpm} 2.5 and 6.5 {\textpm} 2.1 n/frame), compared to controls (P \&lt; .001). DC density was significantly increased in FECD (57.8 {\textpm} 10.4 cells/mm; P\&nbsp;= .01), but not in PBK (47.7 {\textpm} 11.6 cells/mm; P\&nbsp;= .60) compared to controls (22.5 {\textpm} 4.5 cells/mm). A subset of early FECD patients\&nbsp;(7/22) demonstrated very high DC density (\&gt;100/mm). CONCLUSION: IVCM demonstrates profound diminishment of subbasal corneal nerves in early- and late-stage FECD and in PBK, correlating to decreased sensation. Increased DC density in early FECD demonstrates potential subclinical inflammation. The data suggest that reduction in subbasal nerves and increased immune activation may play a role in the pathophysiology of FECD.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.08.040},
	author = {Aggarwal, Shruti and Cavalcanti, Bernardo M and Regali, Laura and Cruzat, Andrea and Trinidad, Monique and Williams, Candice and Jurkunas, Ula V and Hamrah, Pedram}
}
@article {1517175,
	title = {Correlation of corneal immune cell changes with clinical severity in dry eye disease: An in vivo confocal microscopy study},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 Jun 03},
	abstract = {PURPOSE: To evaluate corneal immune dendritiform cell (DC) changes in dry eye disease (DED) using in vivo confocal microscopy (IVCM) and to correlate IVCM parameters with clinical severity. METHODS: This was a retrospective, cross-sectional study including 300 eyes of 150 DED patients and 49 eyes of 49 age-matched controls. Severity of DED was based on the Dry Eye Workshop (DEWS) classification. IVCM images of subbasal layer of the central cornea were analyzed for DC density and morphology (including number of dendrites per DC, DC size and DC field). RESULTS: DC density was significantly higher in DED compared to controls (93.4\&nbsp;{\textpm}\&nbsp;6.3 vs. 25.9\&nbsp;{\textpm}\&nbsp;3.9\&nbsp;cells/mm; P\&nbsp;\&lt;\&nbsp;0.001). Morphologically, number of dendrites, DC size and field were significantly larger in DED (3.3\&nbsp;{\textpm}\&nbsp;0.1, 106.9\&nbsp;{\textpm}\&nbsp;4.7\&nbsp;μm, 403.8\&nbsp;{\textpm}\&nbsp;20.1\&nbsp;μm than controls (2.3\&nbsp;{\textpm}\&nbsp;0.1, 62.5\&nbsp;{\textpm}\&nbsp;5.7\&nbsp;μm, 241.4\&nbsp;{\textpm}\&nbsp;24.4\&nbsp;μm, P\&nbsp;\&lt;\&nbsp;0.001). Significantly higher DC density compared to controls was observed as early as Level 1 DED severity (87\&nbsp;{\textpm}\&nbsp;10\&nbsp;cells/mm, p\&nbsp;\&lt;\&nbsp;0.001. Significant morphological changes in DC were detected for Levels 2 to 4 (p=\&lt;0.001, and p\&nbsp;=\&lt;\&nbsp;0.05) for dendrites and DC field, respectively. Similarly, DC size showed significant increase at DED level 3-4. (p\&nbsp;\&lt;\&nbsp;0.05). Linear regression analysis showed that both conjunctival and corneal staining were independently associated with DC density, while corneal staining was independently associated with DC morphology. CONCLUSION: DC density and morphology correlated with clinical severity of DED. While, DC density is increased in mild DED, morphological changes are seen only in severe cases. IVCM may be a powerful tool to detect early immune changes and may complement clinical examination in DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.05.012},
	author = {Aggarwal, Shruti and Kheirkhah, Ahmad and Cavalcanti, Bernardo M and Cruzat, Andrea and Jamali, Arsia and Hamrah, Pedram}
}
@article {591271,
	title = {Exophiala phaeomuriformis Fungal Keratitis: Case Report and In Vivo Confocal Microscopy Findings},
	journal = {Eye Contact Lens},
	volume = {43},
	number = {2},
	year = {2017},
	month = {2017 Mar},
	pages = {e4-e6},
	abstract = {PURPOSE: Corneal infections, particularly fungal keratitis due to rare fungal species, pose a diagnostic and therapeutic challenge because of difficulty in identification and varying susceptibility profiles. In this study, we report the first case of fungal keratitis because of Exophiala phaeomuriformis. METHODS: We report the clinical findings and microbial identification techniques of a case of fungal keratitis due to E. phaeomuriformis. An 84-year-old woman presented with redness, pain, and itching in the left eye for 2 weeks. Slit-lamp biomicroscopy revealed one broken suture from previous penetrating keratoplasty (PKP), black infiltrates at the 4-o{\textquoteright}clock position, without an overlying epithelial defect and hypopyon. Microbial identification was based cultures on Sabouraud dextrose agar and DNA sequencing and correlations to laser in vivo confocal microscopy (IVCM; Heidelberg Retinal Tomograph 3/Rostock Cornea Module, Heidelberg Engineering) and multiphoton microscopy (Ultima Microscope; Prairie Technologies) images. RESULTS: Slit-lamp biomicroscopy revealed one broken suture from previous PKP, black infiltrates at the 4-o{\textquoteright}clock position, without an overlying epithelial defect and hypopyon. Based on a clinical suspicion of fungal keratitis, antifungals and fortified antibiotics were started. However, the patient did not respond to therapy and required urgent PKP. After surgery, the patient was maintained on topical and systemic voriconazole and also topical 2\% cyclosporine for 5 months because of possibility of scleral involvement noticed during surgery. At the end of the treatment period, her vision improved from hand motion to 20/40, with no recurrence observed in a follow-up period of 1 year. Results of diagnostic tests were supported by fungal elements in stroma on IVCM. Culture from the infiltrate grew black yeast. DNA sequencing led to the diagnosis of E. phaeomuriformis keratitis. Antifungal susceptibility testing revealed sensitivity to voriconazole. CONCLUSION: This is, to our knowledge, the first reported case of E. phaeomuriformis fungal keratitis. Diagnostic testing included slit-lamp biomicroscopy, which revealed pigmented infiltrates, culture plates grew black yeast, microscopy showed branched fungal hyphae with budding conidia, and physiological features showed tolerance to high temperatures, nitrate assimilation, and ribosomal DNA sequencing. Collectively, these tests demonstrate unique features seen for this microorganism. High suspicion should be kept with pigmented infiltrates and with dark yeast on culture plates. Prompt and aggressive medical management with voriconazole or therapeutic PKP in nonresponsive cases is essential to prevent irreversible loss of vision.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000193},
	author = {Aggarwal, Shruti and Yamaguchi, Takefumi and Dana, Reza and Hamrah, Pedram}
}
@article {1417548,
	title = {Efficacy of autologous serum tears for treatment of neuropathic corneal pain},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Jan 24},
	abstract = {OBJECTIVE: Corneal nerve damage may result in neuropathic corneal pain (NCP). Autologous serum tears (AST) have been shown to results in nerve regeneration and may help alleviate corneal pain. This study aimed to evaluate the efficacy of AST in the treatment of NCP. METHODS: This was a retrospective case-control study. Sixteen patients suffering from severe NCP and no current ocular surface disease were compared to 12 controls. In vivo confocal microscopy (IVCM) (HRT3/RCM; Heidelberg, Germany) of the central corneas was performed bilaterally. Change in pain severity (scale of 0-10), corneal nerve density, tortuosity, reflectivity and presence of beading and microneuromas before and after treatment were recorded. RESULTS: All patients had severe pain of 9.1 {\textpm} 0.2 (range 8-10). Before treatment, subbasal nerves were significantly decreased compared to controls, including total nerve length (10,935.5 {\textpm} 1264.3 vs. 24,714.4 {\textpm} 1056.2 μm/mm; p \&lt; 0.0001) and total number of nerves (10.5 {\textpm} 1.4 vs. 28.6 {\textpm} 2.0; p \&lt; 0.0001), respectively. Morphologically, significantly increased reflectivity (2.9 {\textpm} 0.2 vs. 1.2 {\textpm} 0.1; p = 0.00008) and tortuosity (2.4 {\textpm} 0.2 vs. 1.7 {\textpm} 0.1; p = 0.001), both graded on a scale of 0-4, were noted. After 3.8 {\textpm} 0.5 months (range 1-8 months) of AST treatment, pain severity decreased to 3.1 {\textpm} 0.3 (range 0-4), (p \&lt; 0.0001). Further, IVCM demonstrated a significant improvement (p \&lt; 0.005) in total nerve length (17,351.3 {\textpm} 1395.6 μm/mm) and number (15.1 {\textpm} 1.6) as well as significant decrease in reflectivity (2.4 {\textpm} 0.2; p = 0.001) and tortuosity (2.2 {\textpm} 0.2; p = 0.001). CONCLUSION: IVCM demonstrates underlying alterations of the subbasal corneal nerve plexus in patients suffering from debilitating NCP. AST-induced nerve regeneration is seen following treatment with AST, which correlates with improvement in patient symptoms of NCP.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.01.009},
	author = {Aggarwal, Shruti and Colon, Clara and Kheirkhah, Ahmad and Hamrah, Pedram}
}
@article {280916,
	title = {Bilateral adult epibulbar xanthogranulomas suspicious for Erdheim-Chester disease.},
	journal = {Cornea},
	volume = {33},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {1113-7},
	abstract = {PURPOSE: The aim of this study was to report the clinical, imaging, and histopathological findings of bilateral, conjunctival adult-onset xanthogranulomas that raised the prospect of a mild form of Erdheim-Chester disease. METHODS: This is a case report. RESULTS: A 35-year-old white male complaining of ocular irritation, presented with bilateral, nasal and temporal, yellow, elevated conjunctival lumps first noticed 1.5 years back, which were not associated with other ocular findings. The lesions were firm, attached to the underlying episclera, and measured 1.1 {\texttimes} 0.9, 1.1 {\texttimes} 0.8, 1.2 {\texttimes} 0.5, and 0.5 {\texttimes} 0.5 cm in the temporal and nasal right and left eyes, respectively. Each mass was fleshy with vascularity at the peripheral margin. Histopathologic evaluation after excisional biopsy revealed lipidized xanthoma cells, multiple Touton giant cells, and lymphocytes. Immunohistochemical staining was positive for adipophilin (lipid), CD68, CD163 histiocytes, CD3 T cells (with CD8 cytotoxic T cells \&gt; CD4 T-helper cells), and virtually no CD20 B cells or IgG4 plasma cells. The patient later acquired similar xanthogranulomatous subcutaneous lesions on the extremities. Positron emission tomography scans showed sclerosis in the medullary cavities of the tibia and the radius of both legs and arms, and an absence of retroperitoneal lesions. A normal serum immunoelectrophoresis and the absence of a BRAF gene mutation were demonstrated. CONCLUSIONS: Adult-onset xanthogranuloma can present as a solitary conjunctival mass without periocular or orbital involvement. The clinical, histopathologic, and radiologic findings in this case are suggestive of Erdheim-Chester disease without displaying any life-threatening lesions to date. Histopathologic and imaging studies can help in obtaining a diagnosis. Ophthalmologists should be aware that xanthogranulomatous conditions may have potential systemic implications, and a thorough systemic evaluation is recommended for lesions that initially seemed to be isolated in nature.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000191},
	author = {Aggarwal, Shruti and Jakobiec, Frederick A and Hamrah, Pedram}
}
@article {1532377,
	title = {A guarded light pipe for direct visualization during primary scleral buckling on the Ngenuity platform},
	journal = {Int J Retina Vitreous},
	volume = {6},
	year = {2020},
	month = {2020},
	pages = {42},
	abstract = {Background: Visualization during scleral buckling is traditionally achieved via indirect ophthalmoscopy. Recent advances have utilized the surgical microscope and a 25 gauge cannula-based endoillumination system, also known as a Chandelier lighting system. This report details an improved approach using a guarded 25 or 27 gauge light pipe and the Ngenuity digital three dimensional platform. Methods: A standard Alcon light pipe is modified with a silicone guard to expose only 5\&nbsp;mm of the tip of the light pipe. The guard is created from the silicone that is already opened to secure the ends of the encircling band most often employed sleeve (e.g. 70, 270). This guarded light pipe is then inserted into the cannula as an alternative to a Chandelier lighting system. Results: This is a technical report of a surgical visualization technique using a three dimensional digital visualization platform with a modified handheld vitrectomy light pipe. Conclusion: The utilization of a guarded light pipe for visualization during primary scleral buckling is a promising, effective, and efficient technique. The three dimensional digital display allows for better educational impact and surgical communication with trainees and ancillary members of the surgical team.},
	issn = {2056-9920},
	doi = {10.1186/s40942-020-00246-9},
	author = {Agranat, Joshua S and Douglas, Vivian P and Douglas, Konstantinos Aa and Miller, John B}
}
@article {1328872,
	title = {The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Description of the Spectrum of Choroidal Involvement in 245 Patients with Tubercular Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2018},
	month = {2018 Aug 29},
	pages = {1-11},
	abstract = {PURPOSE: To contribute a global description of the spectrum of choroidal involvement in tubercular uveitis (TBU). METHODS: Retrospective cohort study of TBU patients with choroidal involvement from 25 centers between January 2004 and December 2014. Medical records of patients with a minimum follow-up of 1\&nbsp;year were reviewed. RESULTS: 245 patients were included. The phenotypic variations included serpiginous-like choroiditis (SLC) (46\%), tuberculoma (13.5\%), multifocal choroiditis (MFC) (9.4\%), ampiginous choroiditis (9\%), among others. 219 patients were treated with anti-tubercular therapy (ATT) (n\&nbsp;=\&nbsp;219/245, 89.38\%), 229 patients with steroids (n\&nbsp;=\&nbsp;229/245, 93.47\%) and 28 patients with immunosuppressive agents (n\&nbsp;=\&nbsp;28/245, 11.42\%). Treatment failure was noted in 38 patients (n\&nbsp;=\&nbsp;38/245, 15.5\%). Patients with SLC and ampiginous choroiditis appeared to have superior outcomes on survival analysis (p\&nbsp;=\&nbsp;0.06). CONCLUSION: This study provides a comprehensive description of choroidal involvement in TBU. Patients with SLC and ampiginous choroiditis may have better clinical outcomes.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2018.1489061},
	author = {Agrawal, Rupesh and Gunasekeran, Dinesh Visva and Agarwal, Aniruddha and Carre{\~n}o, Ester and Aggarwal, Kanika and Gupta, Bhaskar and Raje, Dhananjay and Murthy, Somasheila I and Westcott, Mark and Chee, Soon Phaik and McCluskey, Peter and Ling, Ho Su and Teoh, Stephen and Cimino, Luca and Biswas, Jyotirmay and Narain, Shishir and Agarwal, Manisha and Mahendradas, Padmamalini and Khairallah, Moncef and Jones, Nicholas and Tugal-Tutkun, Ilknur and Babu, Kalpana and Basu, Soumayava and Lee, Richard and Al-Dhibi, Hassan and Bodaghi, Bahram and Invernizzi, Alessandro and Goldstein, Debra A and Herbort, Carl P and Barisani-Asenbauer, Talin and Gonz{\'a}lez-L{\'o}pez, Julio J and Androudi, Sofia and Bansal, Reema and Moharana, Bruttendu and Mahajan, Sarakshi and Esposti, Simona and Tasiopoulou, Anastasia and Nadarajah, Sengal and Agarwal, Mamta and Abraham, Sharanya and Vala, Ruchi and Lord, Joanne and Singh, Ramandeep and Sharma, Aman and Sharma, Kusum and Zierhut, Manfred and Kon, Onn Min and Kempen, John and Cunningham, Emmett T and Rousselot, Andres and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali}
}
@article {1580462,
	title = {Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis},
	journal = {Ophthalmology},
	volume = {128},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {266-276},
	abstract = {TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. DISCUSSION: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.01.008},
	author = {Agrawal, Rupesh and Testi, Ilaria and Mahajan, Sarakshi and Yuen, Yew Sen and Agarwal, Aniruddha and Kon, Onn Min and Barisani-Asenbauer, Talin and Kempen, John H and Gupta, Amod and Jabs, Douglas A and Smith, Justine R and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali and Collaborative Ocular Tuberculosis Study Consensus Group}
}
@article {1478348,
	title = {Standardization of Nomenclature for Ocular Tuberculosis - Results of Collaborative Ocular Tuberculosis Study (COTS) Workshop},
	journal = {Ocul Immunol Inflamm},
	year = {2019},
	month = {2019 Dec 10},
	pages = {1-11},
	abstract = {: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2019.1653933},
	author = {Agrawal, Rupesh and Agarwal, Aniruddha and Jabs, Douglas A and Kee, Aera and Testi, Ilaria and Mahajan, Sarakshi and McCluskey, Peter J and Gupta, Amod and Palestine, Alan and Denniston, Alastair and Banker, Alay and Invernizzi, Alessandro and Fonollosa, Alex and Sharma, Aman and Kumar, Amitabh and Curi, Andre and Okada, Annabelle and Schlaen, Ariel and Heiligenhaus, Arnd and Kumar, Atul and Gurbaxani, Avinash and Bodaghi, Bahram and Islam Shah, Bulbul and Lowder, Careen and Tappeiner, Christoph and Muccioli, Cristina and Vasconcelos-Santos, Daniel Vitor and Goldstein, Debra and Behra, Digambar and Das, Dipankar and Makhoul, Dorine and Baglivo, Edoardo and Denisova, Ekaterina and Miserocchi, Elisabetta and Carreno, Ester and Asyari, Fatma and Pichi, Francesco and Sen, H Nida and Uy, Harvey and Nascimento, Heloisa and Tugal-Tutkun, Ilknur and Arevalo, J Fernando and Davis, Janet and Thorne, Jennifer and Hisae Yamamoto, Joyce and Smith, Justine and Garweg, Justus G and Biswas, Jyotirmay and Babu, Kalpana and Aggarwal, Kanika and Cimino, Luca and Kuffova, Lucia and Agarwal, Mamta and Zierhut, Manfred and Agarwal, Manisha and DeSmet, Marc and Tognon, Maria Sofia and Errera, Marie-Helene and Munk, Marion and Westcott, Mark and Soheilian, Masoud and Accorinti, Massimo and Khairallah, Moncef and Nguyen, Myhanh and Kon, Onn Minn and Mahendradas, Padmamalini and Yang, Peizeng and Neri, Piergiorgio and Ozdal, Pinar and Amer, Radgonde and Lee, Richard and Distia Nora, Rina La and Chhabra, Romi and Belfort, Rubens and Mehta, Salil and Shoughy, Samir and Luthra, Saurabh and Mohamed, Shelina Oli and Chee, Soon-Phaik and Basu, Soumyava and Teoh, Stephen and Ganesh, Sudha and Barisani-Asenbauer, Talin and Guex-Crosier, Yan and Ozyazgan, Y{\i}lmaz and Akova, Yonca and Habot-Wilner, Zohar and Kempen, John and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali and Collaborative Ocular Tuberculosis Study (COTS) Group}
}
@article {1504087,
	title = {The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Apr 06},
	pages = {1-11},
	abstract = {An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1716025},
	author = {Agrawal, Rupesh and Testi, Ilaria and Mahajan, Sarakshi and Yuen, Yew Sen and Agarwal, Aniruddha and Rousselot, Andres and Raje, Dhananjay and Gunasekeran, Dinesh Visva and Kon, Onn Min and Barisani-Asenbauer, Talin and Kempen, John H and Gupta, Amod and Jabs, Douglas A and Smith, Justine R and Bodaghi, Bahram and Zierhut, Manfred and DeSmet, Marc and McCluskey, Peter and Agarwal, Mamta and Agarwal, Manisha and Aggarwal, Kanika and Agrawal, Mukesh and Al-Dhibi, Hassan and Androudi, Sofia and Asyari, Fatma and Balasundaram, Manohar Babu and Murthy, Kalpana Babu and Baglivo, Edoardo and Banker, Alay and Bansal, Reema and Basu, Soumyava and Behera, Digamber and Biswas, Jyotirmay and Carre{\~n}o, Ester and Caspers, Laure and Chee, Soon Phaik and Chhabra, Romi and Cimino, Luca and Del Rio, Luz Elena Concha and Cunningham, Emmett T and Curi, Andr{\`e} Luiz Land and Das, Dipankar and Denisova, Ekaterina and Denniston, Alastair K and Errera, Marie-H{\'e}l{\`e}ne and Fonollosa, Alejandro and George, Amala and Goldstein, Debra A and Crosier, Yan Guex and Gurbaxani, Avinash and Invernizzi, Alessandro and Isa, Hazlita M and Md Islam, Shah and Jones, Nicholas and Katoch, Deeksha and Khairallah, Moncef and Khosla, Amit and Kramer, Michal and Kumar, Amitabh and Kumar, Atul and Distia Nora, Rina La and Lee, Richard and Lowder, Careen and Luthra, Saurabh and Mahendradas, Padmamalini and Makhoul, Dorine and Mazumdar, Shahana and Mehta, Salil and Miserocchi, Elisabetta and Mochizuki, Manabu and Mohamed, Oli S and Muccioli, Cristina and Munk, Marion R and Murthy, Somasheila and Narain, Shishir and Nascimento, Heloisa and Neri, Piergiorgio and Nguyen, Myhanh and Okada, Annabelle A and Ozdal, Pinar and Palestine, Alan and Pichi, Francesco and Rathinam, S R and Schlaen, Ariel and Sehgal, Shobha and Sen, H Nida and Sharma, Aman and Sharma, Kusum and Shoughy, Samir S and Singh, Nirbhai and Singh, Ramandeep and Soheilian, Masoud and Sridharan, Sudharshan and Thorne, Jennifer E and Tappeiner, Christoph and Teoh, Stephen and Tognon, Maria Sofia and Tugal-Tutkun, Ilknur and Tyagi, Mudit and Uy, Harvey and Santos, Daniel Vitor Vasconcelos and Valentincic, Natasa Vidovic and Westcott, Mark and Yanai, Ryoji and Alvarez, Bety Yanez and Zahedur, Rahman and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali}
}
@article {1549023,
	title = {The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 447 Patients with Tubercular Intermediate Uveitis and Panuveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Nov 17},
	pages = {1-11},
	abstract = {Tubercular intermediate uveitis (TIU) and panuveitis (TBP) are difficult to manage because of limitations in diagnostic tools and lack of evidence-based treatment guidelines. The Collaborative Ocular Tuberculosis Study (COTS) analyzed treatment regimens and therapeutic outcomes in patients with TIU and TBP. Multicentre retrospective analysis. A total of 138 TIU and 309 TBP patients were included. A total of 382 subjects received antitubercular therapy (ATT) (n\&nbsp;=\&nbsp;382/447; 85.4\%) and 382 received corticosteroids (n\&nbsp;=\&nbsp;382/447; 85.4\%). Treatment failure was observed in 78 individuals (n\&nbsp;=\&nbsp;78/447; 17.4\%), occurring less frequently in patients receiving ATT (n\&nbsp;=\&nbsp;66/382; 17.2\%) compared to those who did not (n\&nbsp;=\&nbsp;12/65; 18.5\%). The study did not show any statistically significant therapeutic effect of ATT in patients with TIU and TBP. Taking into account the limitations of the retrospective, non-randomized study design, resultant reliance on reported data records, and unequal size of the samples, the current study cannot provide conclusive evidence on the therapeutic benefit of ATT in TIU and TBP.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1808226},
	author = {Agrawal, Rupesh and Betzler, Bjorn Kaijun and Testi, Ilaria and Mahajan, Sarakshi and Agarwal, Aniruddha and Gunasekeran, Dinesh Visva and Raje, Dhananjay and Aggarwal, Kanika and Murthy, Somasheila I and Westcott, Mark and Chee, Soon-Phaik and McCluskey, Peter and Ho, Su Ling and Teoh, Stephen and Cimino, Luca and Biswas, Jyotirmay and Narain, Shishir and Agarwal, Manisha and Mahendradas, Padmamalini and Khairallah, Moncef and Jones, Nicholas and Tugal-Tutkun, Ilknur and Babu, Kalpana and Basu, Soumayava and Carre{\~n}o, Ester and Lee, Richard and Al-Dhibi, Hassan and Bodaghi, Bahram and Invernizzi, Alessandro and Goldstein, Debra A and Barisani-Asenbauer, Talin and Gonz{\'a}lez-L{\'o}pez, Julio J and Androudi, Sofia and Bansal, Reema and Moharana, Bruttendu and Esposti, Simona Degli and Tasiopoulou, Anastasia and Nadarajah, Sengal and Agarwal, Mamta and Abraham, Sharanaya and Vala, Ruchi and Singh, Ramandeep and Sharma, Aman and Sharma, Kusum and Zierhut, Manfred and Kon, Onn Min and Cunningham, Emmett T and Kempen, John H and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali}
}
@article {1645485,
	title = {The Collaborative Ocular Tuberculosis Study (COTS) calculator-a consensus-based decision tool for initiating antitubercular therapy in ocular tuberculosis},
	journal = {Eye (Lond)},
	volume = {37},
	number = {7},
	year = {2023},
	month = {2023 May},
	pages = {1416-1423},
	abstract = {OBJECTIVE: To introduce the Collaborative Ocular Tuberculosis Study (COTS) Calculator, an online clinical scoring system for initiating antitubercular therapy (ATT) in patients with ocular tuberculosis (TB). METHOD: The COTS Calculator was derived from COTS Consensus (COTS CON) data, which has previously published consensus guidelines. Using a two-step Delphi method, 81 experts evaluated 486 clinical scenario-based questions, ranking their likelihood of initiating ATT in each specific scenario. Each scenario was a permutation of the results and/or availability of five following components-clinical phenotype, endemicity, two immunological (tuberculin skin test, interferon-γ release assay) and one radiological (chest X-Ray) test results-and a sixth component further stratifying three of the clinical phenotypes. The median scores and interquartile ranges (IQR) of each scenario were tabulated, representing the expert consensus on whether to initiate ATT in that scenario. The consensus table was encoded to develop the COTS Calculator. RESULTS: The COTS Calculator can be accessed online at: https://www.oculartb.net/cots-calc . The attending physician can select the conditions present in the patient, which will generate a median score from 1 to 5. 114 out of 486 scenarios (24\%) deliberated had a median score of 5 indicating expert consensus to initiate ATT. CONCLUSION: The COTS Calculator is an efficient, low-cost, evidence and experience-based clinical tool to guide ATT initiation. While it holds substantial promise in improving standard-of-care for ocular-TB patients, future validation studies can help to as certain its clinical utility and reliability.},
	keywords = {Antitubercular Agents, Cognition, Consensus, Humans, Reproducibility of Results, Tuberculosis, Ocular},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-02147-7},
	author = {Agrawal, Rupesh and Ludi, Zhang and Betzler, Bjorn K and Testi, Ilaria and Mahajan, Sarakshi and Rousellot, Andres and Kempen, John H and Smith, Justine R and McCluskey, Peter and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali}
}
@article {1580474,
	title = {Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis},
	journal = {Ophthalmology},
	volume = {128},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {277-287},
	abstract = {TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists{\textquoteright} opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.06.052},
	author = {Agrawal, Rupesh and Testi, Ilaria and Bodaghi, Baharam and Barisani-Asenbauer, Talin and McCluskey, Peter and Agarwal, Aniruddha and Kempen, John H and Gupta, Amod and Smith, Justine R and De Smet, Marc D and Yuen, Yew Sen and Mahajan, Sarakshi and Kon, Onn Min and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali and Collaborative Ocular Tuberculosis Study Consensus Group}
}
@article {1517174,
	title = {Evolving consensus for immunomodulatory therapy in non-infectious uveitis during the COVID-19 pandemic},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {5},
	year = {2021},
	month = {2021 05},
	pages = {639-647},
	abstract = {BACKGROUND: Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged. METHODS: A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine. RESULTS: Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups. CONCLUSION: Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic.},
	keywords = {Clinical Decision-Making, Consensus, COVID-19, Cross-Sectional Studies, Glucocorticoids, Humans, Immunomodulation, Immunosuppressive Agents, Practice Guidelines as Topic, Risk Assessment, SARS-CoV-2, Surveys and Questionnaires, Uveitis},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316776},
	author = {Agrawal, Rupesh and Testi, Ilaria and Lee, Cecilia S and Tsui, Edmund and Blazes, Marian and Thorne, Jennifer E and Okada, Annabelle A and Smith, Justine R and McCluskey, Peter J and Kempen, John H and Tappeiner, Christoph and Agarwal, Manisha and Bodaghi, Bahram and Nguyen, Quan Dong and Gupta, Vishali and De Smet, Marc D and Zierhut, Manfred and Pavesio, Carlos and COVID-19 IMT Study Group}
}
@article {1517439,
	title = {Visual Morbidity in Ocular Tuberculosis - Collaborative Ocular Tuberculosis Study (COTS)-1: Report $\#$6},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	pages = {1-9},
	author = {Agrawal R MD, FCRS and Gunasekeran DV MBBS and Agarwal A MS and Testi I MD and Carre{\~n}o E MD and Westcott M FRCOphth and Mahajan S MBBS and Raje D PhD and Aggarwal K MS and Murthy SI DNB and Chee SP FRCSEd and Mccluskey P MD and Ho SL FRCSGlasg and Teoh S FRCSEd and Cimino L MD and Biswas J MS and Narain S MD and Agarwal M MS and Mahendradas P DNB and Khairallah M MD and Jones N FRCSOphth and Tugal-Tutkun I MD and Babu K DNB and Basu S MS and Lee R PhD and Al-Dhibi H MD and Bodaghi B MD and Invernizzi A MD and Goldstein DA MD and Herbort CP MD and Barisani-Asenbauer T PhD and Gonz{\'a}lez-L{\'o}pez JJ PhD and Androudi S MD and Bansal R MS and Moharana B MS and Esposti SD MD and Tasiopoulou A MD and Nadarajah S MD and Agarwal M DNB and Abraham S MD and Vala R MD and Singh R MS and Sharma A MD and Sharma K PhD and Zierhut M PhD and Kon OM MRCP and Cunningham ET PhD and Kempen JH PhD and Nguyen QD PhD and Pavesio C FRCSOphth and Gupta V MS}
}
@article {1109761,
	title = {Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?},
	journal = {Transl Stroke Res},
	year = {2017},
	month = {2017 Jun 10},
	abstract = {Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3\&nbsp;days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the development of cerebellar damage following preterm IVH. IVH was associated with a decreased proliferative (Ki67-positive) portion of the external granular layer (EGL), delayed Purkinje cell maturation, and activated microglia in the cerebellar white matter. In pups with IVH, immunolabeling of the cerebellum at P0 demonstrated a widespread presence of cell-free Hb, primarily distributed in the white matter and the molecular layer. Intraventricular injection of the Hb scavenger haptoglobin (Hp) resulted in a corresponding distribution of immunolabeled Hp in the cerebellum and a partial reversal of the damaging effects observed following IVH. The results suggest that cell-free Hb is causally involved in cerebellar damage following IVH and that blocking cell-free Hb may have protective effects.},
	issn = {1868-601X},
	doi = {10.1007/s12975-017-0539-1},
	author = {Agyemang, Alex Adusei and Sveinsd{\'o}ttir, Kristbj{\"o}rg and Vallius, Suvi and Sveinsd{\'o}ttir, Snjolaug and Bruschettini, Matteo and Romantsik, Olga and Hellstr{\"o}m, Ann and Smith, Lois E H and Ohlsson, Lennart and Holmqvist, Bo and Gram, Magnus and Ley, David}
}
@article {1615221,
	title = {Nuclear IMPDH Filaments in Human Gliomas},
	journal = {J Neuropathol Exp Neurol},
	year = {2021},
	month = {2021 Sep 08},
	abstract = {The analysis of nuclear morphology plays an important role in glioma diagnosis and grading. We previously described intranuclear rods (rods) labeled with the SDL.3D10 monoclonal antibody against class III beta-tubulin (TUBB3) in human ependymomas. In a cohort of adult diffuse gliomas, we identified nuclear rods in 71.1\% of IDH mutant lower-grade gliomas and 13.7\% of IDH wild-type glioblastomas (GBMs). The presence of nuclear rods was associated with significantly longer postoperative survival in younger (<=65) GBM patients. Consistent with this, nuclear rods were mutually exclusive with Ki67 staining and their prevalence in cell nuclei inversely correlated with the Ki67 proliferation index. In addition, rod-containing nuclei showed a relative depletion of lamin B1, suggesting a possible association with senescence. To gain insight into their functional significance, we addressed their antigenic properties. Using a TUBB3-null mouse model, we demonstrate that the SDL.3D10 antibody does not bind TUBB3 in rods but recognizes an unknown antigen. In the present study, we show that rods show immunoreactivity for the nucleotide synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase. By analogy with the IMPDH filaments that have been described previously, we postulate that rods regulate the activity of nucleotide-synthesizing enzymes in the nucleus by sequestration, with important implications for glioma behavior.},
	issn = {1554-6578},
	doi = {10.1093/jnen/nlab090},
	author = {Ahangari, Narges and Munoz, David G and Coulombe, Josee and Gray, Douglas A and Engle, Elizabeth C and Cheng, Long and Woulfe, John}
}
@article {1667695,
	title = {Global Disparities in Retinopathy of Prematurity: A Literature Review},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {151-157},
	abstract = {PURPOSE: To provide an overview of the impact of retinopathy of prematurity (ROP), and the challenges in the screening, diagnosis, and treatment of ROP worldwide. METHODS: A comprehensive search was conducted using the PubMed database from January 2011 to October 2021 using the following keywords: retinopathy of prematurity, laser, and anti-vascular endothelial growth factor (VEGF). Data on patient characteristics, ROP treatment type, and recurrence rates were collected. The countries included in these studies were classified based on 2021-2022 World Bank definitions of high, upper-middle, lower-middle, and low-income groups. Moreover, a search for surgical outcomes for ROP and screening algorithms and artificial intelligence for ROP was conducted. RESULTS: Thirty-nine studies met the inclusion criteria. ROP treatment and outcomes showed a trend towards intravitreal anti-VEGF injections as the initial treatment for ROP globally and the treatment of recurrent ROP in high-income countries. However, laser remains the treatment of choice for ROP recurrence in middle-income countries. Surgical outcomes for ROP stage 4A, 4B and 5 are similar worldwide. The incidence of ROP and ROP-related visual impairment continue to increase globally. Although telemedicine and artificial intelligence offer potential solutions to ROP screening in resource-limited areas, the current models require further optimization to reflect the global diversity of ROP patients. CONCLUSION: ROP screening and treatment paradigms vary widely based on country income group due to disparities in resources, limited access to care, and lack of universal guidelines.},
	keywords = {Angiogenesis Inhibitors, Artificial Intelligence, Gestational Age, Humans, Infant, Newborn, Intravitreal Injections, Laser Coagulation, Retinopathy of Prematurity, Vascular Endothelial Growth Factor A},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152708},
	author = {Ahmed, Ishrat and Hoyek, Sandra and Patel, Nimesh A}
}
@article {1798336,
	title = {Democratizing Health Care in the Metaverse: How Video Games can Monitor Eye Conditions Using the Vision Performance Index: A Pilot Study},
	journal = {Ophthalmol Sci},
	volume = {4},
	number = {1},
	year = {2024},
	month = {2024 Jan-Feb},
	pages = {100349},
	abstract = {OBJECTIVE: In a world where digital media is deeply engrained into our everyday lives, there lies an opportunity to leverage interactions with technology for health and wellness. The Vision Performance Index (VPI) leverages natural human-technology interaction to evaluate visual function using visual, cognitive, and motor psychometric data over 5 domains: field of view, accuracy, multitracking, endurance, and detection. The purpose of this study was to describe a novel method of evaluating holistic visual function through video game-derived VPI score data in patients with specific ocular pathology.

DESIGN: Prospective comparative analysis.

PARTICIPANTS: Patients with dry eye, glaucoma, cataract, diabetic retinopathy (DR), age-related macular degeneration, and healthy individuals.

METHODS: The Vizzario Inc software development kit was integrated into 2 video game applications, Balloon Pop and Picture Perfect, which allowed for generation of VPI scores. Study participants were instructed to play rounds of each video game, from which a VPI score was compiled.

MAIN OUTCOME MEASURES: The primary outcome was VPI overall score in each comparison group. Vision Performance Index component, subcomponent scores, and psychophysical inputs were also compared.

RESULTS: Vision Performance Index scores were generated from 93 patients with macular degeneration (n~= 10), cataract (n~= 10), DR (n~= 15), dry eye (n~= 15), glaucoma (n~= 16), and no ocular disease (n~= 27). The VPI overall score was not significantly different across comparison groups. The VPI subcomponent "reaction accuracy" score was significantly greater in DR patients (106 {\textpm} 13.2) versus controls (96.9 {\textpm} 11.5), P~= 0.0220. The VPI subcomponent "color detection" score was significantly lower in patients with DR (96.8 {\textpm} 2.5; p=0.0217) and glaucoma (98.5 {\textpm} 6.3; P~= 0.0093) compared with controls (101 {\textpm} 11). Psychophysical measures were statistically significantly different from controls: proportion correct (lower in DR, age-related macular degeneration), contrast errors (higher in cataract, DR), and saturation errors (higher in dry eye).

CONCLUSIONS: Vision Performance Index scores can be generated from interactions of an ocular disease population with video games. The VPI may offer utility in monitoring select ocular diseases through evaluation of subcomponent and psychophysical input scores; however, future larger-scale studies must evaluate the validity of this tool.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100349},
	author = {Ahmed, Yusuf and Reddy, Mohan and Mederos, Jacob and McDermott, Kyle C and Varma, Devesh K and Ludwig, Cassie A and Ahmed, Iqbal K and Khaderi, Khizer R}
}
@article {1179156,
	title = {Association of Disease Location and Treatment With Survival in Diffuse Large B-Cell Lymphoma of the Eye and Ocular Adnexal Region},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {10},
	year = {2017},
	month = {2017 Oct 01},
	pages = {1062-1068},
	abstract = {Importance: Primary diffuse large B-cell lymphoma (DLBCL) of the ocular region is rare, and the utility of surgery and radiation therapy remains unresolved. Objective: To explore the clinical characteristics and determine factors associated with overall survival in primary vitreoretinal lymphoma (PVRL) and ocular adnexal (OA)-uveal DLBCL. Design, Setting, and Participants: This retrospective analysis included 396 patients with ophthalmic DLBCL from January 1, 1973, through December 31, 2014, using the Surveillance, Epidemiology, and End Results database. The median follow-up was 39.0 months (interquartile range, 5.1-72.9 months). All patients diagnosed with primary DLBCL of the eye or retina (PVRL) or the eyelid, conjunctiva, choroid, ciliary body, lacrimal gland, or orbit (OA-uveal lymphoma) were included. Patients diagnosed at autopsy or with additional neoplastic disease were excluded. Main Outcomes and Measures: Patient demographic characteristics, disease location, treatment modalities, and overall survival. Results: Forty-seven patients with PVRL (24 women [51.1\%] and 23 men [48.9\%]) and 349 with OA-uveal DLBCL (192 women [55.0\%] and 157 men [45.0\%]) had a similar mean (SD) age at diagnosis (69.6 [12.3] vs 66.1 [17.7] years). No difference in the use of surgery or radiation therapy by location was found. For all PVRL and OA-uveal DLBCL, a Cox proportional hazards regression model affirmed that age older than 60 years was associated with increased risk for death (hazard ratio [HR], 2.7; 95\% CI, 1.9-4.0; P \&lt; .001). Gross total resection was associated with a decreased risk for death (HR, 0.5; 95\% CI, 0.3-0.9; P = .04), whereas radiation therapy was not. The 5-year overall survival among patients with PVRL was 41.4\% (SE, 8.6\%); among those with OA-uveal DLBCL, 59.1\% (SE, 2.8\%; Mantel-Cox test, P = .007). Median overall survival was lower in PVRL (38.0 months; 95\% CI, 14.2-61.8 months) than in OA-uveal DLBCL (96.0 months; 95\% CI, 67.3-124.7 months; Mantel-Cox test, P = .007). In addition, median overall survival in ophthalmic-only disease was higher (84.0 months; 95\% CI, 63.2-104.8 months) than that in primary DLBCL that occurred outside the central nervous system and ophthalmic regions (46.0 months; 95\% CI, 44.4-47.6 months; Mantel-Cox test, P \&lt; .001). Conclusions and Relevance: The 5-year survival in PVRL vs OA-uveal DLBCL differed by 17.7\%, and overall survival was greater in ophthalmic DLBCL than in DLBCL located outside the central nervous system and ophthalmic regions. Younger age (<=60 years) and gross total resection were associated with increased survival.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.3286},
	author = {Ahmed, Aseef H and Foster, C Stephen and Shields, Carol L}
}
@article {1347423,
	title = {Comparison of Early Treatment Diabetic Retinopathy Study Standard 7-Field Imaging With Ultrawide-Field Imaging for Determining Severity of Diabetic Retinopathy},
	journal = {JAMA Ophthalmol},
	year = {2018},
	month = {2018 Oct 18},
	abstract = {Importance: Moderate to substantial agreement between Early Treatment Diabetic Retinopathy Study (ETDRS) 7-field imaging and ultrawide-field (UWF) imaging has been suggested in single-center studies. Comparing images obtained by multiple centers could increase confidence that UWF images can be used reliably in place of ETDRS imaging in future clinical trials. Objective: To compare diabetic retinopathy (DR) severity from modified ETDRS 7-field imaging and UWF imaging. Design, Setting, and Participants: This preplanned, cross-sectional analysis included modified ETDRS 7-field images obtained using the Diabetic Retinopathy Clinical Research Network acquisition protocol and UWF images obtained captured with the Optos 200Tx system (Optos, PLC) from adult participants (>=18 years old) with type 1 or type 2 diabetes. Both image types were evaluated by trained graders masked to clinical data. Data collection occurred from February 2015 to December 2015, and data analysis from June 2016 to December 2017. Main Outcomes and Measures: Agreement between UWF images, UWF imagesmasked to include only the ETDRS 7-field area, and ETDRS 7-field images were calculated using κ statistics. Results: A total of 764 eyes from 385 participants were included; participants had a median (IQR) age of 62.2 (53.6-69.2) years, 194 (50.4\%) were women, and 256 (66.5\%) were white. Of 742 eyes with both ETDRS 7-field images and UWF masked images graded, 359 (48.4\% [95\% CI, 44.4\%-52.4\%]) eyes had exact agreement, and 653 eyes (88.0\% [95\% CI, 85.2\%-90.3\%]) agreed within 1 step (weighted κ, 0.51 [95\% CI, 0.44-0.58]). After open adjudication by an independent senior grader of all images with more than a 2-step discrepancy, perfect agreement was found in 435 eyes (59.0\% [95\% CI, 55.1\%-62.8\%]) and agreement within 1 step in 714 eyes (96.9\% [95\% CI, 95.1\%-98.0\%]; κ, 0.77 [95\% CI, 0.73-0.82]). Ability of the imaging modalities to detect retinopathy severity in an individual eye was considered similar in 59 eyes (50.9\% [95\% CI, 41.3\%-60.4\%]), better for ETDRS 7-field imaging in 22 eyes (19.0\% [95\% CI, 12.5\%-27.7\%]), and better for UWF-masked images in 31 eyes (26.7\% [95\% CI 18.8\%-36.5\%]). Comparing UWF masked and unmasked images, 94 of 751 eyes (12.5\%) had DR graded as at least 1 step more severe on UWF unmasked images vs UWF masked images. Predominantly peripheral DR lesions were present in 308 of 751 eyes (41.0\%); this suggested increased DR severity by 2 or more steps in 34 eyes (11.0\%). Conclusions and Relevance: Imaging by the ETDRS 7-field and UWF imaging systems have moderate to substantial agreement when determining the severity of DR within the 7 standard fields. Disparities in an individual eye are equivalently distributed between imaging modalities and can be better or worse on 1 or the other. Longitudinal follow-up will evaluate the primary outcome of this study to determine if peripheral retinal findings are associated with future retinopathy outcomes.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.4982},
	author = {Aiello, Lloyd Paul and Odia, Isoken and Glassman, Adam R and Melia, Michele and Jampol, Lee M and Bressler, Neil M and Kiss, Szilard and Silva, Paolo S and Wykoff, Charles C and Sun, Jennifer K and Diabetic Retinopathy Clinical Research Network}
}
@article {1732601,
	title = {Integrating Macular Optical Coherence Tomography with Ultrawide Field Imaging in a Diabetic Retinopathy Telemedicine Program Using a Single Device},
	journal = {Retina},
	year = {2023},
	month = {2023 Jul 04},
	abstract = {PURPOSE: To determine the effect of combined macular optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program. METHODS: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. UWFI and SD-OOCT were independently evaluated for diabetic macular edema (DME) and non-diabetic macular pathology. Sensitivity and specificity were calculated with SD-OCT as gold standard. RESULTS: 422 eyes from 211 diabetic patients were evaluated. DME severity by UWFI: no DME 93.4\%, non-center involved DME (nonciDME) 5.1\%, ciDME 0.7\%, ungradable DME 0.7\%. SD-OCT was ungradable in 0.5\%. Macular pathology was identified in 34 (8.1\%) eyes by UWFI and in 44 (10.4\%) eyes by SD-OCT. DME represented only 38.6\% of referable macular pathology identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared to SD-OCT was 59\%/96\% for DME and 33\%/99\% for ciDME. Sensitivity/specificity of UWFI compared to SDOCT was 3\%/98\% for ERM. CONCLUSIONS: Addition of SD-OCT increased the identification of macular pathology by 29.4\%. Over 58.3\% of the eyes thought to have any DME on UWF imaging alone were false positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false positive assessments of DME and macular pathology in a teleophthalmology program.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003883},
	author = {Aiello, Lloyd Paul and Jacoba, Cris Martin P and Ashraf, Mohamed and Cavallerano, Jerry D and Tolson, Ann M and Tolls, Dot and Sun, Jennifer K and Silva, Paolo S}
}
@article {1483603,
	title = {Long-Term Effect on HbA1c in Poorly Controlled Diabetic Patients Following Nonmydriatic Retinal Image Review at the Time of Endocrinology Visit},
	journal = {Telemed J E Health},
	volume = {26},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {1265-1270},
	abstract = {p p p},
	issn = {1556-3669},
	doi = {10.1089/tmj.2019.0239},
	author = {Aiello, Lloyd Paul and Cavallerano, Jerry and Sun, Jennifer and Nisreen Salti and Nasrallah, Mona and Mehanna, Carl Joe and El Salloukh, Nasrine Anais and Salti, Haytham I}
}
@article {439671,
	title = {Assessing the Effect of Personalized Diabetes Risk Assessments During Ophthalmologic Visits on Glycemic Control: A Randomized Clinical Trial.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {8},
	year = {2015},
	month = {2015 Aug 1},
	pages = {888-96},
	abstract = {IMPORTANCE: Optimization of glycemic control is critical to reduce the number of diabetes mellitus-related complications, but long-term success is challenging. Although vision loss is among the greatest fears of individuals with diabetes, comprehensive personalized diabetes education and risk assessments are not consistently used in ophthalmologic settings. OBJECTIVE: To determine whether the point-of-care measurement of hemoglobin A1c (HbA1c) and personalized diabetes risk assessments performed during retinal ophthalmologic visits improve glycemic control as assessed by HbA1c level. DESIGN, SETTING, AND PARTICIPANTS: Ophthalmologist office-based randomized, multicenter clinical trial in which investigators from 42 sites were randomly assigned to provide either a study-prescribed augmented diabetes assessment and education or the usual care. Adults with type 1 or 2 diabetes enrolled into 2 cohorts: those with a more-frequent-than-annual follow-up (502 control participants and 488 intervention participants) and those with an annual follow-up (368 control participants and 388 intervention participants). Enrollment was from April 2011 through January 2013. INTERVENTIONS: Point-of-care measurements of HbA1c, blood pressure, and retinopathy severity; an individualized estimate of the risk of retinopathy progression derived from the findings from ophthalmologic visits; structured comparison and review of past and current clinical findings; and structured education with immediate assessment and feedback regarding participant{\textquoteright}s understanding. These interventions were performed at enrollment and at routine ophthalmic follow-up visits scheduled at least 12 weeks apart. MAIN OUTCOMES AND MEASURES: Mean change in HbA1c level from baseline to 1-year follow-up. Secondary outcomes included body mass index, blood pressure, and responses to diabetes self-management practices and attitudes surveys. RESULTS: In the cohort with more-frequent-than-annual follow-ups, the mean (SD) change in HbA1c level at 1 year was -0.1\% (1.5\%) in the control group and -0.3\% (1.4\%) in the intervention group (adjusted mean difference, -0.09\% [95\% CI, -0.29\% to 0.12\%]; P = .35). In the cohort with annual follow-ups, the mean (SD) change in HbA1c level was 0.0\% (1.1\%) in the control group and -0.1\% (1.6\%) in the intervention group (mean difference, -0.05\% [95\% CI, -0.27\% to 0.18\%]; P = .63). Results were similar for all secondary outcomes. CONCLUSIONS AND RELEVANCE: Long-term optimization of glycemic control is not achieved by a majority of individuals with diabetes. The addition of personalized education and risk assessment during retinal ophthalmologic visits did not result in a reduction in HbA1c level compared with usual care over 1 year. These data suggest that optimizing glycemic control remains a substantive challenge requiring interventional paradigms other than those examined in our study. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01323348.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.1312},
	author = {Aiello, Lloyd Paul and Ayala, Allison R and Antoszyk, Andrew N and Arnold-Bush, Bambi and Baker, Carl and Bressler, Neil M and Elman, Michael J and Glassman, Adam R and Jampol, Lee M and Melia, Michele and Nielsen, Jared and Wolpert, Howard A and Diabetic Retinopathy Clinical Research Network}
}
@article {1782381,
	title = {INTEGRATING MACULAR OPTICAL COHERENCE TOMOGRAPHY WITH ULTRAWIDE-FIELD IMAGING IN A DIABETIC RETINOPATHY TELEMEDICINE PROGRAM USING A SINGLE DEVICE},
	journal = {Retina},
	volume = {43},
	number = {11},
	year = {2023},
	month = {2023 Nov 01},
	pages = {1928-1935},
	abstract = {PURPOSE: To determine the effect of combined macular spectral-domain optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program. METHODS: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. Ultrawide field retinal imaging and SD-OOCT were independently evaluated for diabetic macular edema (DME) and nondiabetic macular abnormality. Sensitivity and specificity were calculated with SD-OCT as the gold standard. RESULTS: Four hundred twenty-two eyes from 211 diabetic patients were evaluated. Diabetic macular edema severity by UWFI was as follows: no DME 93.4\%, noncenter involved DME (nonciDME) 5.1\%, ciDME 0.7\%, ungradable DME 0.7\%. SD-OCT was ungradable in 0.5\%. Macular abnormality was identified in 34 (8.1\%) eyes by UWFI and in 44 (10.4\%) eyes by SD-OCT. Diabetic macular edema represented only 38.6\% of referable macular abnormality identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared with SD-OCT was 59\%/96\% for DME and 33\%/99\% for ciDME. Sensitivity/specificity of UWFI compared with SDOCT was 3\%/98\% for epiretinal membrane. CONCLUSION: Addition of SD-OCT increased the identification of macular abnormality by 29.4\%. More than 58.3\% of the eyes believed to have any DME on UWF imaging alone were false-positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false-positive assessments of DME and macular abnormality in a teleophthalmology program.},
	keywords = {Cohort Studies, Diabetes Mellitus, Diabetic Retinopathy, Humans, Macular Edema, Ophthalmology, Retrospective Studies, Telemedicine, Tomography, Optical Coherence},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003883},
	author = {Aiello, Lloyd Paul and Jacoba, Cris Martin P and Ashraf, Mohamed and Cavallerano, Jerry D and Tolson, Ann M and Tolls, Dorothy and Sun, Jennifer K and Silva, Paolo S}
}
@article {1761796,
	title = {Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol},
	journal = {BMJ Open Ophthalmol},
	volume = {8},
	number = {1},
	year = {2023},
	month = {2023 Sep},
	abstract = {INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.},
	keywords = {Cohort Studies, Corneal Transplantation, Endothelial Cells, Endothelium, Corneal, Humans, Multicenter Studies as Topic, Surgeons, Trypan Blue},
	issn = {2397-3269},
	doi = {10.1136/bmjophth-2023-001361},
	author = {Airaldi, Matteo and Zheng, Yalin and Aiello, Francesco and Bachmann, Bj{\"o}rn and Baydoun, Lamis and N{\'\i} Dhubhghaill, Sorcha and Dickman, Mor M and Kaye, Stephen B and Fontana, Luigi and Gadhvi, Kunal A and Moramarco, Antonello and de Mora, Marina Rodriguez Calvo and Rocha de Lossada, Carlos and Scorcia, Vincenzo and Viola, Pietro and Calza, Stefano and Levis, Hannah J and Parekh, Mohit and Ruzza, Alessandro and Ferrari, Stefano and Ponzin, Diego and Semeraro, Francesco and Romano, Vito}
}
@article {1490447,
	title = {Free and hydrogel encapsulated exosome-based therapies in regenerative medicine},
	journal = {Life Sci},
	volume = {249},
	year = {2020},
	month = {2020 May 15},
	pages = {117447},
	abstract = {Over the last few decades, mesenchymal stem cells-derived exosomes (MSCs-Ex) have attracted a lot of attention as a therapeutic tool in regenerative medicine. Exosomes are extracellular vehicles (EVs) that play important roles in cell-cell communication through various processes such as stress response, senescence, angiogenesis, and cell differentiation. Success in the field of regenerative medicine sparked exploration of the potential use of exosomes as key therapeutic effectors of MSCs to promote tissue regeneration. Various approaches including direct injection, intravenous injection, intraperitoneal injection, oral administration, and hydrogel-based encapsulation have been exploited to deliver exosomes to target tissues in different disease models. Despite significant advances in exosome therapy, it is unclear which approach is more effective for administering exosomes. Herein, we critically review the emerging progress in the applications of exosomes in the form of free or association with hydrogels as therapeutic agents for applications in regenerative medicine.},
	keywords = {Animals, Exosomes, Humans, Hydrogels, Mesenchymal Stem Cells, Regenerative Medicine},
	issn = {1879-0631},
	doi = {10.1016/j.lfs.2020.117447},
	author = {Akbari, Ali and Jabbari, Nassrollah and Sharifi, Roholah and Ahmadi, Mahdi and Vahhabi, Ali and Seyedzadeh, Seyyed Javad and Nawaz, Muhammad and Szafert, S{\l}awomir and Mahmoodi, Monireh and Jabbari, Esmaiel and Asghari, Rahim and Rezaie, Jafar}
}
@article {1651232,
	title = {Density and distribution of dendritiform cells in the peripheral cornea of healthy subjects using in vivo confocal microscopy},
	journal = {Ocul Surf},
	year = {2022},
	author = {Akhlaq, A and Col{\'o}n, C and Cavalcanti, BM and Aggarwal, S and Qazi, Y and Cruzat, A and Jersey, C and Critser, DB and Watts, A and J. Beyer and Sindt, CW and Hamrah, P}
}
@article {1761891,
	title = {A Simplified Model of Activation and Deactivation of Human Rod Phototransduction-An Electroretinographic Study},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {12},
	year = {2023},
	month = {2023 Sep 01},
	pages = {36},
	abstract = {PURPOSE: To test the hypothesis that a simple model having properties consistent with activation and deactivation in the rod approximates the whole time course of the photoresponse. METHODS: Routinely, an exponential of the form f = α{\textperiodcentered}(1 - exp(-(τ{\textperiodcentered}(t - teff)s-1))), with amplitude α, rate constant τ (often scaled by intensity), irreducible delay teff, and time exponent s-1, is fit to the early period of the flash electroretinogram. Notably, s (an integer) represents the three integrating stages in the rod amplification cascade (rhodopsin isomerization, transducin activation, and cGMP hydrolysis). The time course of the photoresponse to a 0.17 cd{\textperiodcentered}s{\textperiodcentered}m-2 conditioning flash (CF) was determined in 21 healthy eyes by presenting the CF plus a bright probe flash (PF) in tandem, separated by interstimulus intervals (ISIs) of 0.01 to 1.4 seconds, and calculating the proportion of the PF a-wave suppressed by the CF at each ISI. To test if similar kinetics describe deactivation, difference of exponential (DoE) functions with common α and teff parameters, respective rate constants for the initiation (I) and quenching (Q) phases of the response, and specified values of s (sI, sQ), were compared to the photoresponse time course. RESULTS: As hypothesized, the optimal values of sI and sQ were 3 and 2, respectively. Mean {\textpm} SD α was 0.80 {\textpm} 0.066, I was 7700 {\textpm} 2400 m2{\textperiodcentered}cd-1{\textperiodcentered}s-3, and Q was 1.4 {\textpm} 0.47 s-1. Overall, r2 was 0.93. CONCLUSIONS: A method, including a DoE model with just three free parameters (α, I, Q), that robustly captures the magnitude and time-constants of the complete rod response, was produced. Only two steps integrate to quench the rod photoresponse.},
	keywords = {Cognition, Cyclic GMP, Electroretinography, Eye, Humans, Light Signal Transduction},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.12.36},
	author = {Akula, James D and Lancos, Annie M and AlWattar, Bilal K and De Bruyn, Hanna and Hansen, Ronald M and Fulton, Anne B}
}
@article {1470980,
	title = {Extracting the ON and OFF contributions to the full-field photopic flash electroretinogram using summed growth curves},
	journal = {Exp Eye Res},
	volume = {189},
	year = {2019},
	month = {2019 Dec},
	pages = {107827},
	abstract = {Under cone-mediated (photopic) conditions, an "instantaneous" flash of light, including both stimulus onset and offset, will simultaneously activate both "ON" and "OFF" bipolar cells, which either depolarize (ON) or hyperpolarize (OFF) in response and, respectively, produce positive-going and negative-going deflections in the electroretinogram (ERG). The stimulus-response (SR) relationship of the photopic ON response demonstrates logistic growth, like that manifested in the rod-mediated (scotopic) b-wave, which is driven by a single class of depolarizing bipolar cell. However, the photopic b-wave SR function is importantly shaped by OFF responses, leading to a "photopic hill." Furthermore, both on and off stimuli elicit activity in both ON and OFF bipolar cells. This has made it difficult to produce meaningful parameters for ready interpretation of the photopic b-wave SR relationship. Therefore, we evaluated whether the sum of sigmoidal SR functions, as descriptors of the depolarizing and hyperpolarizing components of the photopic flash ERG, could be used to elucidate and quantitate the mechanisms that produce the photopic hill. We used a novel fitting routine to optimize a sum of simple sigmoidal curves to SR data in five groups of subjects: Healthy adult, 10-week-old infant, congenital stationary night blindness (CSNB), X-linked juvenile retinoschisis (XJR), and preterm-born, both without and with a history of retinopathy of prematurity (ROP). Differences in ON and OFF amplitude, sensitivity, and implicit time among the groups were then compared using parameters extracted from these fits. We found that our modeling procedure enabled plausible derivations of ON and OFF pathway contributions to the ERG, and that the parameters produced appeared to have physiological relevance. In adult subjects, the ON and OFF amplitudes were similar in magnitude with respectively longer and shorter implicit times. Infant, CSNB, and XJR subjects showed significant ON pathway deficits. History of preterm-birth, without or with a diagnosis of ROP, did not much affect cone responses.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.107827},
	author = {Akula, James D and Ambrosio, Lucia and Howard, Fiona I and Hansen, Ronald M and Fulton, Anne B}
}
@article {1532335,
	title = {The Fovea in Retinopathy of Prematurity},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {11},
	year = {2020},
	month = {2020 Sep 01},
	pages = {28},
	abstract = {Purpose: Because preterm birth and retinopathy of prematurity (ROP) are associated with poor visual acuity (VA) and altered foveal development, we evaluated relationships among the central retinal photoreceptors, postreceptor retinal neurons, overlying fovea, and VA in ROP. Methods: We obtained optical coherence tomograms (OCTs) in preterm born subjects with no history of ROP (none; n = 61), ROP that resolved spontaneously without treatment (mild; n = 51), and ROP that required treatment by laser ablation of the avascular peripheral retina (severe; n = 22), as well as in term born control subjects (term; n = 111). We obtained foveal shape descriptors, measured central retinal layer thicknesses, and demarcated the anatomic parafovea using automated routines. In subsets of these subjects, we obtained OCTs eccentrically through the pupil (n = 46) to reveal the fiber layer of Henle (FLH) and obtained adaptive optics scanning light ophthalmograms (AO-SLOs) of the parafoveal cones (n = 34) and measured their spacing and distribution. Results: Both VA and foveal depth decreased with increasing ROP severity (term, none, mild, severe). In severe subjects, foveae were broader than normal and the parafovea was significantly enlarged compared to every other group. The FLH was thinner than normal in mild (but not severe) subjects. VA was associated with foveal depth more than group. Density of parafoveal cones did not differ significantly among groups. Conclusions: Foveal structure is associated with loss of VA in ROP. The preserved FLH in severe (relative to mild) eyes suggests treatment may help cone axon development. The significantly larger parafovea and increased outer nuclear layer (ONL) thickness in ROP hint that some developmental process affecting the photoreceptors is not arrested in ROP but rather is supranormal.},
	issn = {1552-5783},
	doi = {10.1167/iovs.61.11.28},
	author = {Akula, James D and Arellano, Ivana A and Swanson, Emily A and Favazza, Tara L and Bowe, Theodore S and Munro, Robert J and Ferguson, R Daniel and Hansen, Ronald M and Moskowitz, Anne and Fulton, Anne B}
}
@article {1367191,
	title = {Localization of sleep spindles, k-complexes, and vertex waves with subdural electrodes in children},
	journal = {J Clin Neurophysiol},
	volume = {31},
	number = {4},
	year = {2014},
	pages = {367-74},
	author = {Pinto AL and Fern{\'a}ndez IS and Peters JM and Manganaro S and Singer JM and Vendrame M and Prabhu SP and Loddenkemper T and Kothare SV}
}
@article {935661,
	title = {Fornix-Based Versus Limbal-Based Conjunctival Trabeculectomy Flaps for Glaucoma: Findings From a Cochrane Systematic Review},
	journal = {Am J Ophthalmol},
	volume = {174},
	year = {2017},
	month = {2017 Feb},
	pages = {33-41},
	abstract = {PURPOSE: To compare effectiveness of fornix- and limbal-based conjunctival flaps in trabeculectomy surgery. DESIGN: Systematic review. METHODS: Setting: CENTRAL, MEDLINE, LILACS, ISRCTN registry, ClinicalTrials.gov, WHO, and ICTRP were searched to identify eligible randomized controlled trials (RCTs). STUDY POPULATION: RCTs in which benefits and complications of fornix- vs limbal-based trabeculectomy for glaucoma were compared in adult glaucoma patients. OBSERVATION PROCEDURE: We followed Cochrane methodology for data extraction. MAIN OUTCOME MEASURES: Proportion of failed trabeculectomies at 24\&nbsp;months, defined as the need for repeat surgery or uncontrolled intraocular pressure (IOP) \&gt;22\&nbsp;mm Hg, despite topical/systemic medications. RESULTS: The review included 6 trials with a total of 361 participants, showing no difference in effectiveness between fornix-based vs limbal-based trabeculectomy surgery, although with a high level of uncertainty owing to low event rates. In the fornix-based and limbal-based surgery, mean IOP at 12\&nbsp;months was similar, with ranges of 12.5-15.5\&nbsp;mm Hg and 11.7-15.1\&nbsp;mm Hg, respectively. Mean difference was 0.44\&nbsp;mm Hg (95\% CI\&nbsp;-0.45 to 1.33) and 0.86\&nbsp;mm Hg (95\% CI\&nbsp;-0.52 to 2.24) at 12 and 24\&nbsp;months of follow-up, respectively. Mean number of postoperative glaucoma medications was similar between the 2 groups. Mean difference was 0.02 (95\% CI\&nbsp;-0.15 to 0.19) at 12\&nbsp;months. As far as postoperative complications, an increased risk of shallow anterior chamber was observed in the limbal-based group. CONCLUSION: Similar efficacy of trabeculectomy surgery with respect to bleb failure or IOP control was observed in both types of conjunctival flap incisions. A significant difference was detected in the risk of postoperative shallow anterior chamber, which was increased in the limbal-based group.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.10.006},
	author = {Al-Haddad, Christiane E and Abdulaal, Marwan and Al-Moujahed, Ahmad and Ervin, Ann-Margret and Ismail, Karine}
}
@article {1658690,
	title = {Cost Analysis: Port Delivery System versus Monthly Ranibizumab for Wet Age-Related Macular Degeneration Treatment},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {1105-1106},
	keywords = {Humans, Intravitreal Injections, Ranibizumab, Wet Macular Degeneration},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.05.021},
	author = {Al-Khersan, Hasenin and Patel, Nimesh A and Yannuzzi, Nicolas A and Lin, James and Smiddy, William E}
}
@article {1667723,
	title = {Widefield Fluorescein Angiography Findings in Pediatric Patients with X-Linked Retinoschisis},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {7},
	year = {2023},
	month = {2023 Jul},
	pages = {639-643},
	abstract = {PURPOSE: To evaluate the retinal vasculature in pediatric patients with X-linked retinoschisis (XLRS). DESIGN: Retrospective consecutive case series. SUBJECTS: Pediatric patients with a diagnosis of XLRS who had undergone widefield fluorescein angiography (FA). METHODS: The electronic medical records of pediatric patients with XLRS at a tertiary referral eye center were reviewed from January 2015 to December 2021. Fluorescein angiography images were reviewed for anomalies of the retinal vasculature. MAIN OUTCOMES MEASURES: Vascular anomalies on FA were recorded, including capillary dropout/ischemia, terminal supernumerary vessels, vascular leakage, abnormal vascular loops, straightening of vessels, aberrant circumferential vessels, and neovascularization. RESULTS: In total, 29 eyes of 15 patients were included in the study (1 patient had a phthisical eye). On FA, the most common findings were capillary dropout/ischemia (21 of 29 eyes, 72.4\%), terminal supernumerary vessels (21 eyes, 72.4\%), abnormal vascular loops (20 eyes, 69\%), and vascular leakage (17 eyes, 58.6\%). Of the 17 eyes with leakage, the most posterior zone of involvement was zone 1 in 11 eyes (64.7\%) and zone 2 in 6 eyes (35.3\%). All eyes demonstrated >= 1 vascular anomaly on FA. Among the 29 eyes, 23 (79.3\%) demonstrated peripheral bullous schisis or retinal detachment (RD) with a mean of 5.6 clock hours of involvement. The presence of either RD or bullous retinal schisis was associated with the incidence of capillary dropout (91.3\% in schisis/RD eyes vs. 0\% in nonschisis/RD eyes, P \&lt; 0.001). Among those with RD or bullous schisis, a higher degree of involvement correlated with more severe capillary dropout (Pearson 0.49, P\&nbsp;=\&nbsp;0.025). CONCLUSION: The present study demonstrates consistent vascular changes in pediatric patients with XLRS using widefield FA. Although the presence of capillary ischemia was associated with the severity of bullous schisis or RD, other vascular anomalies were observed in patients both with and without peripheral schisis. Although further research is needed to understand the etiology of these vascular anomalies, FA should be considered in the evaluation of these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Child, Fluorescein Angiography, Humans, Ischemia, Retinal Detachment, Retinal Vessels, Retinoschisis, Retrospective Studies},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.02.005},
	author = {Al-Khersan, Hasenin and Sengillo, Jesse and Fan, Kenneth C and L{\'o}pez-Ca{\~n}izares, Ashley and da Cruz, Natasha F S and Patel, Nimesh A and Berrocal, Audina M}
}
@article {1364580,
	title = {Antiangiogenic therapy for ischemic retinopathies},
	journal = {Cold Spring Harb Perspect Med},
	volume = {2},
	number = {6},
	year = {2012},
	month = {2012 Jun},
	pages = {a006411},
	abstract = {Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases.},
	keywords = {Angiogenesis Inhibitors, Choroidal Neovascularization, Combined Modality Therapy, Diabetic Retinopathy, Glaucoma, Neovascular, Humans, Laser Coagulation, Macular Degeneration, Retinal Neovascularization, Retinal Vein Occlusion, Vascular Endothelial Growth Factor A, Vitrectomy},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a006411},
	author = {Al-Latayfeh, Motasem and Silva, Paolo S and Sun, Jennifer K and Aiello, Lloyd Paul}
}
@article {1318853,
	title = {Utility of optical coherence tomography in the evaluation of sellar and parasellar mass lesions},
	journal = {Curr Opin Endocrinol Diabetes Obes},
	volume = {25},
	number = {4},
	year = {2018},
	month = {2018 Aug},
	pages = {274-284},
	abstract = {PURPOSE OF REVIEW: Anterior visual pathway compression is a common feature of sellar region masses. We review the visual pathway neuroanatomy pertaining to sellar and parasellar lesions and describe recent advances in optical coherence tomography (OCT) imaging that have provided a novel quantitative perspective in the evaluation and management of such patients. RECENT FINDINGS: Ultrastructural measurements of optic nerve integrity using OCT, namely peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCIPL) thicknesses, have been shown to correlate with visual acuity and visual field deficits on perimetry in patients with compressive sellar region masses. In some cases, OCT can visualize early signs of anterior visual pathway involvement in the absence of clinically evident visual field loss or optic disc pallor. OCT is particularly useful when assessing patients who demonstrate less reliable visual field testing. Furthermore, there is growing awareness that pRNFL and GCIPL thinning preoperatively correlate with worse visual recovery following chiasmal decompression, highlighting the prognostic utility of OCT in this patient population. SUMMARY: OCT provides a complimentary, yet critical, role in quantitatively assessing ultrastructural retinal injury in patients with sellar and parasellar lesions compressing the anterior visual pathway and should be incorporated into routine evaluation.},
	issn = {1752-2978},
	doi = {10.1097/MED.0000000000000415},
	author = {Al-Louzi, Omar and Prasad, Sashank and M Mallery, Robert}
}
@article {1573098,
	title = {Granulicatella Adiacens as an Unusual Cause of Microbial Keratitis and Endophthalmitis: A Case Series and Literature Review},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Jan 10},
	pages = {1-5},
	abstract = {: To report two cases of microbial keratitis and/or endophthalmitis involving : Case series. : 24-year-old female with a history of Herpes simplex virus 1 (HSV-1) and keratitis presented with a geographic epithelial defect and infiltrate in the left eye. Cultures were positive for HSV-1 and . Keratitis resolved with topical vancomycin and oral valacyclovir. A 65-year-old female with a history of type II diabetes and failed therapeutic penetrating keratoplasty presented with inferior corneal graft haze and vitreous inflammation of the right eye. Therapeutic penetrating keratoplasty and pars plana vitrectomy were performed, and the corneal button returned positive for . The patient was treated with topical and intravitreal vancomycin as well as topical and systemic steroids. : These cases expand the literature on keratitis and endophthalmitis and corroborate the role of steroid use and prior surgery as paramount risk factors.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1860233},
	author = {Al-Lozi, Amal and Cai, Sophie and Chen, Xi and Perez, Victor L and Venkateswaran, Nandini}
}
@article {1789231,
	title = {Toric Monofocal Intraocular Lenses for the Correction of Astigmatism during Cataract Surgery: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	year = {2023},
	month = {2023 Dec 25},
	abstract = {PURPOSE: To review the published literature evaluating the visual and refractive outcomes and rotational stability of eyes implanted with toric monofocal intraocular lenses (IOLs) for the correction of keratometric astigmatism during cataract surgery and to compare those outcomes with outcomes of eyes implanted with nontoric monofocal IOLs and other astigmatism management methods performed during cataract surgery. This assessment was restricted to the toric IOLs available in the United States.

METHODS: A literature search of English-language publications in the PubMed database was last conducted in July 2022. The search identified 906 potentially relevant citations, and after review of the abstracts, 63 were selected for full-text review. Twenty-one studies ultimately were determined to be relevant to the assessment criteria and were selected for inclusion. The panel methodologist assigned each a level of evidence rating; 12 studies were rated level I and 9 studies were rated level II.

RESULTS: Eyes implanted with toric IOLs showed excellent postoperative uncorrected distance visual acuity (UCDVA), reduction of postoperative refractive astigmatism, and good rotational stability. Uncorrected distance visual acuity was better and postoperative cylinder was lower with toric IOLs, regardless of manufacturer, when compared with nontoric monofocal IOLs. Correcting pre-existing astigmatism with toric IOLs was more effective and predictable than using corneal relaxing incisions (CRIs), especially in the presence of higher magnitudes of astigmatism.

CONCLUSIONS: Toric monofocal IOLs are effective in neutralizing pre-existing corneal astigmatism at the time of cataract surgery and result in better UCDVA and significant reductions in postoperative refractive astigmatism compared with nontoric monofocal IOLs. Toric IOLs result in better astigmatic correction than CRIs, particularly at high magnitudes of astigmatism.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.10.010},
	author = {Al-Mohtaseb, Zaina and Steigleman, W Allan and Pantanelli, Seth M and Lin, Charles C and Hatch, Kathryn M and Rose-Nussbaumer, Jennifer R and Santhiago, Marcony and Olsen, Timothy W and Kim, Stephen J and Schallhorn, Julie M}
}
@article {1430519,
	title = {Receptor interacting protein kinase 3 (RIP3) regulates iPSCs generation through modulating cell cycle progression genes},
	journal = {Stem Cell Res},
	volume = {35},
	year = {2019},
	month = {2019 Mar},
	pages = {101387},
	abstract = {The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82\%). RNA-seq analysis and qRT-PCR showed that RIP3 KO MEFs expressed lower levels of genes that control cell cycle progression and cell division and higher levels of extracellular matrix-regulating genes. The growth rate of RIP3 KO MEFs was significantly slower than WT MEFs. These findings can partially explain the inhibitory effects of RIP3 deletion on iPSCs generation and show for the first time that the necroptosis kinase RIP3 plays an important role in iPSC reprogramming. In contrast to RIP3, the kinase and scaffolding functions of RIPK1 appeared to have distinct effects on reprogramming.},
	issn = {1876-7753},
	doi = {10.1016/j.scr.2019.101387},
	author = {Al-Moujahed, Ahmad and Tian, Bo and Efstathiou, Nikolaos E and Konstantinou, Eleni K and Hoang, Mien and Lin, Haijiang and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1351128,
	title = {Uveal melanoma cell growth is inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {7},
	year = {2014},
	month = {2014 Apr 29},
	pages = {4175-85},
	abstract = {PURPOSE: To evaluate the effects and mechanism of aminoimidazole carboxamide ribonucleotide (AICAR), an AMP-dependent kinase (AMPK) activator, on the growth of uveal melanoma cell lines. METHODS: Four different cell lines were treated with AICAR (1-4 mM). Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Cell cycle analysis was conducted by flow cytometry; additionally, expression of cell-cycle control proteins, cell growth transcription factors, and downstream effectors of AMPK were determined by RT-PCR and Western blot. RESULTS: Aminoimidazole carboxamide ribonucleotide inhibited cell growth, induced S-phase arrest, and led to AMPK activation. Aminoimidazole carboxamide ribonucleotide treatment was associated with inhibition of eukaryotic translation initiation factor 4E-BP1 phosphorylation, a marker of mammalian target of rapamycin (mTOR) pathway activity. Aminoimidazole carboxamide ribonucleotide treatment was also associated with downregulation of cyclins A and D, but had minimal effects on the phosphorylation of ribosomal protein S6 or levels of the macroautophagy marker LC3B. The effects of AICAR were abolished by treatment with dipyridamole, an adenosine transporter inhibitor that blocks the entry of AICAR into cells. Treatment with adenosine kinase inhibitor 5-iodotubericidin, which inhibits the conversion of AICAR to its 5{\textquoteright}-phosphorylated ribotide 5-aminoimidazole-4-carboxamide-1-D-ribofuranosyl-5{\textquoteright}-monophosphate (ZMP; the direct activator of AMPK), reversed most of the growth-inhibitory effects, indicating that some of AICAR{\textquoteright}s antiproliferative effects are mediated at least partially through AMPK activation. CONCLUSIONS: Aminoimidazole carboxamide ribonucleotide inhibited uveal melanoma cell proliferation partially through activation of the AMPK pathway and downregulation of cyclins A1 and D1.},
	keywords = {Aminoimidazole Carboxamide, Blotting, Western, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cell Survival, Enzyme Activation, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Phosphotransferases (Phosphate Group Acceptor), Real-Time Polymerase Chain Reaction, Ribonucleotides, RNA, Neoplasm, TOR Serine-Threonine Kinases, Uveal Neoplasms},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12856},
	author = {Al-Moujahed, Ahmad and Nicolaou, Fotini and Brodowska, Katarzyna and Papakostas, Thanos D and Marmalidou, Anna and Ksander, Bruce R and Miller, Joan W and Gragoudas, Evangelos and Vavvas, Demetrios G}
}
@article {1137861,
	title = {Verteporfin inhibits growth of human glioma in vitro without light activation},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Aug 08},
	pages = {7602},
	abstract = {Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-07632-8},
	author = {Al-Moujahed, Ahmad and Brodowska, Katarzyna and Stryjewski, Tomasz P and Efstathiou, Nikolaos E and Vasilikos, Ioannis and Cichy, Joanna and Miller, Joan W and Gragoudas, Evangelos and Vavvas, Demetrios G}
}
@article {503931,
	title = {Outcomes of an Algorithmic Approach to Treating Mild Ocular Alkali Burns.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {10},
	year = {2015},
	month = {2015 Oct 1},
	pages = {1214-6},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.2302},
	author = {Al-Moujahed, Ahmad and Chodosh, James}
}
@article {1761921,
	title = {RESCUE INTRAVITREAL METHOTREXATE TREATMENT FOLLOWING EARLY RECOGNITION OF PROLIFERATIVE VITREORETINOPATHY},
	journal = {Retin Cases Brief Rep},
	volume = {17},
	number = {5},
	year = {2023},
	month = {2023 Sep 01},
	pages = {616-619},
	abstract = {PURPOSE: To report a case of proliferative vitreoretinopathy (PVR) in a man with recurrent retinal detachment successfully managed without surgical intervention following the initiation of intravitreal methotrexate injections to arrest progression of PVR. METHODS: Report of a case. RESULTS: A 60-year-old man presented to the retina clinic 4 weeks after undergoing vitrectomy for rhegmatogenous retinal detachment and was found to have an inferior recurrent retinal detachment. He underwent repeat vitrectomy and scleral buckling with successful reattachment of the retina in the immediate postoperative period. At postoperative Week 2, preretinal membranes were noted inferiorly with stretching of the causative retinal break and localized subretinal fluid, consistent with early PVR. The patient underwent immediate laser barricade, and a course of intravitreal methotrexate injections was started. At the final follow-up 7 months later, the retina was fully attached without progression of PVR. CONCLUSION: Intravitreal methotrexate may play a role in arresting progression of early postoperative PVR and obviating the need for surgical intervention.},
	keywords = {Humans, Male, Methotrexate, Middle Aged, Retina, Retinal Detachment, Retrospective Studies, Scleral Buckling, Treatment Outcome, Vitrectomy, Vitreoretinopathy, Proliferative},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001252},
	author = {Alabi, Rolake and Stryjewski, Tomasz P and Vora, Robin A and Eliott, Dean and Moussa, Kareem}
}
@article {1263291,
	title = {Corneal Cross-Linking With Verteporfin and Nonthermal Laser Therapy},
	journal = {Cornea},
	volume = {37},
	number = {3},
	year = {2018},
	month = {2018 Mar},
	pages = {362-368},
	abstract = {PURPOSE: To test whether verteporfin with a nonthermal laser increases corneal mechanical stiffness and resistance to enzymatic degradation ex vivo. METHODS: Thirty human corneas (n = 5 per group) were treated with verteporfin alone (V), irradiated with nonthermal laser therapy (689 nm) alone (NTL), or received combined treatment of verteporfin with nonthermal laser therapy for 1 sequence (V+NTL1) or 6 sequences (V+NTL6) of 1 minute of NTL exposure. Positive controls were pretreated with 0.1\% riboflavin/20\% dextran every 3 to 5 minutes for 30 minutes and irradiated with ultraviolet light type A (λ = 370 nm, irradiance = 3 mW/cm) for 30 minutes using the Dresden protocol (R+UVA). Untreated corneas were used as negative controls. The corneal biomechanical properties were measured with enzymatic digestion, compression, creep, and tensile strength testing. RESULTS: V+NTL6- and R+UVA-treated corneas acquired higher rigidity and more pronounced curvature than untreated corneas. The stress-strain tests showed that V+NTL6 and R+UVA corneas became significantly stiffer than controls (P \&lt; 0.005). The V+NTL6 group seemed to be slightly stiffer than the R+UVA group, although the differences were not statistically significant. V+NTL6 corneas were found to have a significantly lower absolute creep rate (-1.87 vs. -3.46, P \&lt; 0.05) and significantly higher maximum stress values (7.67 vs. 3.02 P \&lt; 0.05) compared with untreated corneas. CONCLUSIONS: Verteporfin-NTL (V+NTL6) increases corneal mechanical stiffness and resistance to enzymatic collagenase degradation. Although a clinical study is needed, our results suggest that V+NTL6 induces corneal cross-linking and corneal biomechanical changes that are similar to those induced by standard corneal collagen cross-linking.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001473},
	author = {Alageel, Saleh A and Arafat, Samer N and Salvador-Culla, Borja and Kolovou, Paraskevi E and Jahanseir, Khadijeh and Kozak, Adam and Braithwaite, Gavin J C and Ciolino, Joseph B}
}
@article {1363238,
	title = {Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography},
	journal = {J Glaucoma},
	volume = {22},
	number = {7},
	year = {2013},
	month = {2013 Sep},
	pages = {532-41},
	abstract = {PURPOSE: To determine the effects of age, sex, and race on the retinal nerve fiber layer (RNFL) in the normal human eye as measured by the spectral domain optical coherence tomography (SD-OCT) Spectralis machine (Heidelberg Engineering). METHODS: Peripapillary SD-OCT RNFL thickness measurements were determined in normal subjects seen at a university-based clinic. One randomly selected eye per subject was used for analysis in this cross-sectional study. Multiple regression analysis was applied to assess the effects of age, sex, ethnicity, and mean refractive error on peripapillary RNFL thickness. Results are expressed as means{\textpm}SD wherever applicable. RESULTS: The study population consisted of 190 healthy participants from 9 to 86 years of age. Of the 190 participants, 62 (33\%) were men, 125 (66\%) Caucasians, 26 (14\%) African Americans, 14 (7\%) Hispanics, 16 (8\%) Asians, and 9 (5\%) other races. The mean RNFL thickness for the normal population studied was 97.3 {\textpm} 9.6 {\textmu}m. Normal RNFL thickness values follow the ISNT rule with decreasing RNFL thickness values starting from the thickest quadrant inferiorly to the thinnest quadrant temporally: inferior quadrant (126 {\textpm} 15.8), superior quadrant (117.2{\textpm}16.13), nasal quadrant (75 {\textpm} 13.9), and temporal quadrant (70.6 {\textpm} 10.8 {\textmu}m). Thinner RNFL measurements were associated with older age (P\&lt;0.001); being Caucasian, versus being either Hispanic or Asian (P=0.02 and 0.009, respectively); or being more myopic (P\&lt;0.001). For every decade of increased age, mean RNFL thickness measured thinner by approximately 1.5 {\textmu}m (95\% confidence interval, 0.24-0.07). Comparisons between ethnic groups revealed that Caucasians had mean RNFL values (96 {\textpm} 9.2 {\textmu}m) slightly thinner than those of Hispanics (102.9 {\textpm} 11 {\textmu}m; P=0.02) or Asians (100.7 {\textpm} 8.5 {\textmu}m; P=0.009). African Americans RNFL values (99.2 {\textpm} 10.2 {\textmu}m) were not significantly different when compared with Caucasians. There was no relationship between RNFL thickness and sex. CONCLUSIONS: The thickest RNFL measurements were found in the inferior quadrant, followed by the superior, nasal, and temporal quadrants (ISNT rule applied to the RNFL). Thinner RNFL measurements were associated with older age and increasing myopia. Caucasians tend to have thinner RNFL values when compared with Hispanics and Asians. SD-OCT analysis of the normal RNFL showed results similar to time domain OCT studies.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Aging, Child, Cross-Sectional Studies, Ethnic Groups, Female, Humans, Male, Middle Aged, Nerve Fibers, Optic Disk, Reference Values, Retinal Ganglion Cells, Retrospective Studies, Sex Factors, Tomography, Optical Coherence, Young Adult},
	issn = {1536-481X},
	doi = {10.1097/IJG.0b013e318255bb4a},
	author = {Alasil, Tarek and Wang, Kaidi and Keane, Pearse A and Lee, Hang and Baniasadi, Neda and de Boer, Johannes F and Chen, Teresa C}
}
@article {1351129,
	title = {Correlation of retinal nerve fiber layer thickness and visual fields in glaucoma: a broken stick model},
	journal = {Am J Ophthalmol},
	volume = {157},
	number = {5},
	year = {2014},
	month = {2014 May},
	pages = {953-59},
	abstract = {PURPOSE: To determine the retinal nerve fiber layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss. DESIGN: Retrospective cross-sectional study. METHODS: Eighty-seven healthy and 108 glaucoma subjects (1 eye per subject) were recruited from an academic institution. All patients had VF examinations (Swedish Interactive Threshold Algorithm 24-2 test of\&nbsp;the Humphrey Visual Field Analyzer 750i) and spectral-domain optical coherence tomography RNFL scans. Comparison of RNFL thickness values with VF threshold values showed a plateau of VF threshold values at high RNFL thickness values and then a sharp decrease at lower RNFL thickness values. A broken stick statistical analysis was used to estimate the tipping point at which RNFL thickness values are associated with VF defects. The slope for the association between structure and function was computed for data above and below the tipping point. RESULTS: The mean RNFL thickness value that was associated with initial VF loss was 89\&nbsp;μm. The superior RNFL thickness value that was associated with initial corresponding inferior VF loss was 100\&nbsp;μm. The inferior RNFL thickness value that was associated with initial corresponding superior VF loss was 73\&nbsp;μm. The differences between all the slopes above and below the aforementioned tipping points were statistically significant (P\&nbsp;\&lt; .001). CONCLUSIONS: In open-angle glaucoma, substantial RNFL thinning or structural loss appears to be necessary before functional visual field defects become detectable.},
	keywords = {Aged, Algorithms, Cross-Sectional Studies, Exfoliation Syndrome, Female, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Middle Aged, Models, Biological, Nerve Fibers, Optic Nerve Diseases, Retinal Ganglion Cells, Retrospective Studies, Tomography, Optical Coherence, Tonometry, Ocular, Vision Disorders, Visual Field Tests, Visual Fields},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.01.014},
	author = {Alasil, Tarek and Wang, Kaidi and Yu, Fei and Field, Matthew G and Lee, Hang and Baniasadi, Neda and de Boer, Johannes F and Coleman, Anne L and Chen, Teresa C}
}
@article {1351130,
	title = {Driving with hemianopia: III. Detection of stationary and approaching pedestrians in a simulator},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {1},
	year = {2014},
	month = {2014 Jan 20},
	pages = {368-74},
	abstract = {PURPOSE: To compare blind-side detection performance of drivers with homonymous hemianopia (HH) for stationary and approaching pedestrians, initially appearing at small (4{\textdegree}) or large (14{\textdegree}) eccentricities in a driving simulator. While the stationary pedestrians did not represent an imminent threat, as their eccentricity increased rapidly as the vehicle advanced, the approaching pedestrians maintained a collision course with approximately constant eccentricity, walking or running, toward the travel lane as if to cross. METHODS: Twelve participants with complete HH and without spatial neglect pressed the horn whenever they detected a pedestrian while driving along predetermined routes in two driving simulator sessions. Miss rates and reaction times were analyzed for 52 stationary and 52 approaching pedestrians. RESULTS: Miss rates were higher and reaction times longer on the blind than the seeing side (P \&lt; 0.01). On the blind side, miss rates were lower for approaching than stationary pedestrians (16\% vs. 29\%, P = 0.01), especially at larger eccentricities (20\% vs. 54\%, P = 0.005), but reaction times for approaching pedestrians were longer (1.72 vs. 1.41 seconds; P = 0.03). Overall, the proportion of potential blind-side collisions (missed and late responses) was not different for the two paradigms (41\% vs. 35\%, P = 0.48), and significantly higher than for the seeing side (3\%, P = 0.002). CONCLUSIONS: In a realistic pedestrian detection task, drivers with HH exhibited significant blind-side detection deficits. Even when approaching pedestrians were detected, responses were often too late to avoid a potential collision.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Automobile Driving, Computer Simulation, Female, Hemianopsia, Humans, Male, Middle Aged, Psychomotor Performance, Reaction Time, Vision, Binocular, Visual Fields, Visual Perception, Young Adult},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12737},
	author = {Alberti, Concetta F and Peli, Eli and Bowers, Alex R}
}
@article {1351131,
	title = {Visual attention measures predict pedestrian detection in central field loss: a pilot study},
	journal = {PLoS One},
	volume = {9},
	number = {2},
	year = {2014},
	month = {2014},
	pages = {e89381},
	abstract = {PURPOSE: The ability of visually impaired people to deploy attention effectively to maximize use of their residual vision in dynamic situations is fundamental to safe mobility. We conducted a pilot study to evaluate whether tests of dynamic attention (multiple object tracking; MOT) and static attention (Useful Field of View; UFOV) were predictive of the ability of people with central field loss (CFL) to detect pedestrian hazards in simulated driving. METHODS: 11 people with bilateral CFL (visual acuity 20/30-20/200) and 11 age-similar normally-sighted drivers participated. Dynamic and static attention were evaluated with brief, computer-based MOT and UFOV tasks, respectively. Dependent variables were the log speed threshold for 60\% correct identification of targets (MOT) and the increase in the presentation duration for 75\% correct identification of a central target when a concurrent peripheral task was added (UFOV divided and selective attention subtests). Participants drove in a simulator and pressed the horn whenever they detected pedestrians that walked or ran toward the road. The dependent variable was the proportion of timely reactions (could have stopped in time to avoid a collision). RESULTS: UFOV and MOT performance of CFL participants was poorer than that of controls, and the proportion of timely reactions was also lower (worse) (84\% and 97\%, respectively; p = 0.001). For CFL participants, higher proportions of timely reactions correlated significantly with higher (better) MOT speed thresholds (r = 0.73, p = 0.01), with better performance on the UFOV divided and selective attention subtests (r = -0.66 and -0.62, respectively, p\&lt;0.04), with better contrast sensitivity scores (r = 0.54, p = 0.08) and smaller scotomas (r = -0.60, p = 0.05). CONCLUSIONS: Our results suggest that brief laboratory-based tests of visual attention may provide useful measures of functional visual ability of individuals with CFL relevant to more complex mobility tasks.},
	keywords = {Adult, Aged, Aged, 80 and over, Attention, Automobile Driving, Humans, Middle Aged, Pilot Projects, Scotoma, Vision, Ocular, Visual Acuity, Visual Fields},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0089381},
	author = {Alberti, Concetta F and Horowitz, Todd and Bronstad, P Matthew and Bowers, Alex R}
}
@article {1645477,
	title = {Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial},
	journal = {Ophthalmology},
	volume = {129},
	number = {10},
	year = {2022},
	month = {2022 10},
	pages = {1177-1191},
	abstract = {PURPOSE: To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human choroideremia (CHM)-encoding cDNA in CHM. DESIGN: Prospective, open-label, nonrandomized, dose-escalation, phase I/II clinical trial. PARTICIPANTS: Fifteen CHM patients (ages 20-57 years at dosing). METHODS: Patients received uniocular subfoveal injections of low-dose (up to 5\&nbsp;{\texttimes} 1010 vector genome [vg] per eye, n\&nbsp;= 5) or high-dose (up to 1\&nbsp;{\texttimes} 1011 vg per eye, n\&nbsp;= 10) of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA (AAV2-hCHM). Patients were evaluated preoperatively and postoperatively for 2 years with ophthalmic examinations, multimodal retinal imaging, and psychophysical testing. MAIN OUTCOME MEASURES: Visual acuity, perimetry (10-2 protocol), spectral-domain OCT (SD-OCT), and short-wavelength fundus autofluorescence (SW-FAF). RESULTS: We detected no vector-related or systemic toxicities. Visual acuity returned to within 15 letters of baseline in all but 2 patients (1 developed acute foveal thinning, and 1 developed a macular hole); the rest showed no gross changes in foveal structure at 2 years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry or in the lateral extent of retinal pigment epithelium relative preservation by SD-OCT and SW-FAF. Microperimetry showed nonsignificant (\&lt; 3 standard deviations of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships. CONCLUSIONS: Visual acuity was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13 of 15 patients. Acute foveal thinning with unchanged perifoveal function in 1 patient and macular hole in 1 patient suggest foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.},
	keywords = {Adult, Choroideremia, Dependovirus, DNA, Complementary, Fluorescein Angiography, Genetic Therapy, Humans, Middle Aged, Prospective Studies, Retinal Perforations, Serogroup, Tomography, Optical Coherence, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.06.006},
	author = {Aleman, Tomas S and Huckfeldt, Rachel M and Serrano, Leona W and Pearson, Denise J and Vergilio, Grace K and McCague, Sarah and Marshall, Kathleen A and Ashtari, Manzar and Doan, Tu M and Weigel-DiFranco, Carol A and Biron, Bethany S and Wen, Xiao-Hong and Chung, Daniel C and Liu, Emily and Ferenchak, Kevin and Morgan, Jessica I W and Pierce, Eric A and Eliott, Dean and Bennett, Jean and Comander, Jason and Maguire, Albert M}
}
@article {1773491,
	title = {The Neuropeptide α-Melanocyte-Stimulating Hormone Prevents Persistent Corneal Edema following Injury},
	journal = {Am J Pathol},
	volume = {194},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {150-164},
	abstract = {Corneal endothelial cells (CEnCs) regulate corneal hydration and maintain tissue transparency through their barrier and pump function. However, these cells exhibit limited regenerative capacity following injury. Currently, corneal transplantation is the only established therapy for restoring endothelial function, and there are no pharmacologic interventions available for restoring endothelial function. This study investigated the efficacy of the neuropeptide α-melanocyte-stimulating hormone (α-MSH) in promoting endothelial regeneration during the critical window between ocular injury and the onset of endothelial decompensation using an established murine model of injury using transcorneal freezing. Local administration of α-MSH following injury prevented corneal edema and opacity, reduced leukocyte infiltration, and limited CEnC apoptosis while promoting their proliferation. These results suggest that α-MSH has a proregenerative and cytoprotective function on CEnCs and shows promise as a therapy for the prevention and management of corneal endothelial dysfunction.},
	keywords = {alpha-MSH, Animals, Cell Line, Cornea, Corneal Edema, Cytoprotection, Endothelial Cells, Female, Humans, Macrophages, Mice, Mice, Inbred BALB C, Monocytes, Neutrophil Infiltration, Pregnancy, Tissue Preservation, Wound Healing},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2023.09.007},
	author = {Alemi, Hamid and Wang, Shudan and Blanco, Tomas and Kahale, Francesca and Singh, Rohan B and Ortiz, Gustavo and Musayeva, Aytan and Yuksel, Erdem and Pang, Kunpeng and Deshpande, Neha and Dohlman, Thomas H and Jurkunas, Ula V and Yin, Jia and Dana, Reza}
}
@article {1761936,
	title = {Insights into mustard gas keratopathy- characterizing corneal layer-specific changes in mice exposed to nitrogen mustard},
	journal = {Exp Eye Res},
	volume = {236},
	year = {2023},
	month = {2023 Nov},
	pages = {109657},
	abstract = {Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3\&nbsp;μL solution of 0.25\&nbsp;mg/mL or 5\&nbsp;mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5\&nbsp;min. Mice were evaluated prior to and after exposure on days 1, 3, 7, 14, and 28 for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation was used to examine corneal cross-sections collected at the completion of follow-up. Following exposure, mice experienced central corneal epithelial erosion and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma in both dosages. The epithelium was recovered by day 3 in the low dose group, followed by exacerbated punctuate erosions alongside persistent corneal edema that arose and continued onward to four weeks post-exposure. The high dose group showed persistent epitheliopathy throughout the study. The endothelial cell density was reduced, more prominent in the high dose group, early after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at 4 weeks post-exposure included dysmorphic basal epithelial cells and reduced epithelial thickness, and in the limbal cornea included decreased cellular layers. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas.},
	keywords = {Animals, Cornea, Corneal Diseases, Corneal Edema, Corneal Ulcer, Humans, Mechlorethamine, Mice, Microscopy, Confocal, Mustard Gas, Vision Disorders},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2023.109657},
	author = {Alemi, Hamid and Dehghani, Shima and Forouzanfar, Katayoon and Surico, Pier Luigi and Narimatsu, Akitomo and Musayeva, Aytan and Sharifi, Sina and Wang, Shudan and Dohlman, Thomas H and Yin, Jia and Chen, Yihe and Dana, Reza}
}
@article {1698321,
	title = {Insights into mustard gas keratopathy: Characterizing corneal layer-specific changes in mice exposed to nitrogen mustard},
	journal = {Exp Eye Res},
	year = {2023},
	month = {2023 May 02},
	pages = {109495},
	abstract = {Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 μL solution of 0.25 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1 and 3, and weekly for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation and immunostaining were used to examine corneal cross-sections collected at the completion of follow-up. A biphasic ocular injury was observed in mice exposed to NM, most prominent in the corneal epithelium and anterior stroma. Following exposure, mice experienced central corneal epithelial erosions and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma. The epithelium was recovered by day 3, followed by exacerbated punctuate erosions alongside persistent stromal edema that arose and continued onward to four weeks post-exposure. The endothelial cell density was reduced on the first day after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at this time included dysmorphic basal epithelial cells, and in the limbal cornea included decreased cellular layers and p63+ area, along with increased DNA oxidization. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas. Our research suggests DNA oxidation contributes to the long-term effects of nitrogen mustard on limbal stem cells.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2023.109495},
	author = {Alemi, Hamid and Dehghani, Shima and Musayeva, Aytan and Nadari, Amirreza and Narimatsu, Akitomo and Sharifi, Sina and Forouzanfar, Katayoun and Wang, Shudan and Dohlman, Thomas H and Yin, Jia and Chen, Yihe and Dana, Reza}
}
@article {1364581,
	title = {In vivo confocal microscopy in dry eye disease and related conditions},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {138-48},
	abstract = {A new era of ocular imaging has recently begun with the advent of in vivo confocal microscopy (IVCM), shedding more light on the pathophysiology, diagnosis, and potential treatment strategies for dry eye disease. IVCM is a noninvasive and powerful tool that allows detection of changes in ocular surface epithelium, immune and inflammatory cells, corneal nerves, keratocytes, and meibomian gland structures on a cellular level. Ocular surface structures in dry eye-related conditions have been assessed and alterations have been quantified using IVCM. IVCM may aid in the assessment of dry eye disease prognosis and treatment, as well as lead to improved understanding of the pathophysiological mechanisms in this complex disease. Further, due to visualization of subclinical findings, IVCM may allow detection of disease at much earlier stages and allow stratification of patients for clinical trials. Finally, by providing an objective methodology to monitor treatment efficacy, image-guided therapy may allow the possibility of tailoring treatment based on cellular changes, rather than on clinical changes alone.},
	keywords = {Dry Eye Syndromes, Eyelid Diseases, Humans, Meibomian Glands, Microscopy, Confocal},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.711416},
	author = {Alhatem, Albert and Cavalcanti, Bernardo and Hamrah, Pedram}
}
@article {1043181,
	title = {Pericardial patch graft repair of severe localized scleral thinning encountered during strabismus surgery},
	journal = {J AAPOS},
	volume = {21},
	number = {2},
	year = {2017},
	month = {2017 Apr},
	pages = {156-156.e1},
	abstract = {This article presents a surgical technique using a pericardial patch for the permanent repair of severe scleral thinning encountered during strabismus surgery. In the present case scleral thinning resulted from buckle removal. Familiarity with this technique may prove important for the strabismus surgeon treating patients with a history of surface ocular hardware or disease-induced scleral thinning. This video article may be viewed atjaapos.org.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2017.03.010},
	author = {Alkharashi, Maan and Dagi, Alexander F and Dagi, Linda R}
}
@article {1789136,
	title = {The efficacy of part-time patching treatment for intermittent exotropia on different age groups},
	journal = {Eur J Ophthalmol},
	year = {2023},
	month = {2023 Dec 06},
	pages = {11206721231218654},
	abstract = {BACKGROUND: Intermittent exotropia (IXT) is one of the most common forms of strabismus usually seen in the pediatric age group, the prevalence of IXT is higher in Africa and the Middle East. IXT treatment strategies include both surgical and non-surgical methods, non-surgical management is preferred in general as it is less invasive and avoids the risks associated with surgery and anesthesia. AIMS: This study aims to determine the effectiveness of patching therapy for the treatment of IXT in different age groups and to compare the success of patching therapy in preventing surgery in IXT patients in different age groups. METHODOLOGY: A retrospective chart review was conducted from September 2022 until February 2023 at King Abdulaziz University Hospital in Riyadh. The data was collected retrospectively from electronic medical records from 2016 to 2021 of all patients diagnosed with IXT and were managed by patching therapy fitting the inclusion criteria. RESULTS: A total of 76 patients with IXT enrolled in the study with 56.5\% of the participants were older than 7 years old. Overall, there was no improvement in the angle of deviation but 34\% of patients had improved control over the follow-up period. 55.3\% of the participants didn{\textquoteright}t require surgery. Younger age, longer duration of patching per month, and good compliance were significantly associated with treatment success. CONCLUSION: Younger age groups were more likely to benefit from patching therapy than older age groups, and good compliance to patching therapy is an important factor in preventing the need for surgery.},
	issn = {1724-6016},
	doi = {10.1177/11206721231218654},
	author = {Alkharashi, Maan and Aldokhayel, Fares and Alekrish, Yazeed and Alotaibi, Mohammed and Almazyad, Laith Mazyad and Bajeaifer, Yazen}
}
@article {1078701,
	title = {Reduced surgical success rate of rectus muscle plication compared to resection},
	journal = {J AAPOS},
	year = {2017},
	month = {2017 May 20},
	abstract = {PURPOSE: To evaluate the surgical success of rectus muscle plication compared to resection and to compare the short- and long-term changes in ocular alignment after both procedures. METHODS: The medical records of all patients who underwent a rectus muscle tightening procedure (resection or plication) at a single institution over a 5-year period by a single surgeon were reviewed retrospectively. Binocular alignment was recorded before and immediately after surgery and again at 6-12 weeks and final follow-up visit. Primary outcome was surgical success rate, defined as distance alignment of <=10(Δ) for horizontal and <=6(Δ) for vertical strabismus. Secondary outcomes were reoperation rate and postoperative alignment drift. RESULTS: A total of 72 surgeries were identified for inclusion: 48 resections and 24 plications. Surgical success was significantly higher in the resection group than in the plication group (89\% vs 58\%; P = 0.005) at both 6-12 weeks{\textquoteright} follow-up (P = 0.005) and at mean final follow-up of 19 {\textpm} 13 months (range, 3-56 months [n = 48]; P = 0.03). Reoperations were performed in 3 patients in the plication group (12.5\%), all for undercorrection; there were no reoperations in the resection group (P = 0.03). CONCLUSIONS: Rectus muscle plication has many potential advantages over resection, including sparing of the ciliary circulation. In our experience, however, patients treated with plication had lower surgical success rates and a higher reoperation rate. Surgeons should monitor their long-term results before considering plication as their procedure of choice over resection.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2017.05.012},
	author = {Alkharashi, Maan and Hunter, David G}
}
@article {987921,
	title = {Available Evidence on Leber Congenital Amaurosis and Gene Therapy.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	month = {2017},
	pages = {14-21},
	abstract = {Leber congenital amaurosis (LCA) is a group of severe inherited retinal dystrophies that lead to early childhood blindness. In the last decade, interest in LCA has increased as advances in genetics have been applied to better identify, classify, and treat LCA. To date, 23 LCA genes have been identified. Gene replacement in the RPE65 form of LCA represents a major advance in treatment, although limitations have been recognized. In this article, we review the clinical and genetic features of LCA and evaluate the evidence available for gene therapy in RPE65 disease.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228383},
	author = {Alkharashi, Maan and Fulton, Anne B}
}
@article {1351132,
	title = {Cauda equina involvement in Susac{\textquoteright}s syndrome},
	journal = {J Neurol Sci},
	volume = {337},
	number = {1-2},
	year = {2014},
	month = {2014 Feb 15},
	pages = {91-6},
	abstract = {Susac{\textquoteright}s syndrome is a rare autoimmune microangiopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. In many cases, the clinical triad is not fully present at the onset of symptoms. MRI studies often show characteristic punched out lesions of the central fibers of the corpus callosum, and leptomeningeal enhancement and deep gray matter lesions may also be seen. Here we present a case of Susac{\textquoteright}s syndrome in a middle aged man with the unique clinical finding of cauda equina syndrome and spinal MRI showing diffuse lumbosacral nerve root enhancement. Biopsy specimens of the brain, leptomeninges, and skin showed evidence of a pauci-immune endotheliopathy, consistent with pathology described in previous cases of Susac{\textquoteright}s syndrome. This case is important not only because it expands the clinical features of Susac{\textquoteright}s syndrome but also because it clarifies the mechanism of a disorder of the endothelium, an important target for many disorders of the nervous system.},
	keywords = {Cauda Equina, Corpus Callosum, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Peripheral Nervous System Diseases, Spinal Cord, Susac Syndrome},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2013.11.023},
	author = {Allmendinger, Andrew M and M Mallery, Robert and Magro, Cynthia M and Wang, Nancy and Egan, Robert A and Samuels, Martin A and Callahan, Alison and Viswanadhan, Narayan and Klufas, Roman A and Hsu, Liangge and Prasad, Sashank}
}
@article {439661,
	title = {Complete Genome Sequence of Linezolid-Susceptible Staphylococcus haemolyticus Sh29/312/L2, a Clonal Derivative of a Linezolid-Resistant Clinical Strain.},
	journal = {Genome Announc},
	volume = {3},
	number = {3},
	year = {2015},
	month = {2015},
	abstract = {We report the whole-genome sequence (WGS) of an in vitro susceptible derivative revertant mutant from a bloodstream isolate involved in a nosocomial outbreak in Brazil. The WGS comprises 2.5\&nbsp;Mb with 2,500 protein-coding sequences, 16rRNA genes, and 60 tRNA genes.},
	issn = {2169-8287},
	doi = {10.1128/genomeA.00494-15},
	author = {de Almeida, Lara M and Pires, Carlos and Cerdeira, Louise T and de Oliveira, Th{\'e}o G M and McCulloch, John Anthony and Perez-Chaparro, Paula Juliana and Sacramento, Andrey G and Brito, Artemir C and da Silva, Jo{\'a}s L and de Ara{\'u}jo, Maria Rita E and Lincopan, Nilton and Martin, Melissa J and Gilmore, Michael S and Mamizuka, Elsa M}
}
@article {1504072,
	title = {Transferable Resistance Gene in Enterococcus faecalis from Swine in Brazil},
	journal = {Antimicrob Agents Chemother},
	volume = {64},
	number = {6},
	year = {2020},
	month = {2020 May 21},
	abstract = {OptrA is an ATP-binding cassette (ABC)-F protein that confers resistance to oxazolidinones and phenicols and can be either plasmid-encoded or chromosomally encoded. Here, we isolated 13 strains possessing a linezolid MIC of >=4 mg/liter from nursery pigs in swine herds located across Brazil. Genome sequence comparison showed that these strains possess in different genetic contexts occurring in 5 different sequence type backgrounds. The gene invariably occurred in association with an regulator and a gene encoding a hypothetical protein. In some contexts, this genetic island was able to excise and form a covalently closed circle within the cell; this circle appeared to occur in high abundance and to be transmissible by coresident plasmids.},
	issn = {1098-6596},
	doi = {10.1128/AAC.00142-20},
	author = {Almeida, Lara M and Lebreton, Fran{\c c}ois and Gaca, Anthony and Bispo, Paulo M and Saavedra, Jose T and Calumby, Rodrigo N and Grillo, Luciano M and Nascimento, Ticiano G and Filsner, Pedro H and Moreno, Andrea M and Gilmore, Michael S}
}
@article {1647887,
	title = {Ocular manifestations of COVID-19 in the pediatric age group},
	journal = {Eur J Ophthalmol},
	volume = {33},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {21-28},
	abstract = {The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular manifestations. The literature thoroughly discussed those that affect adults, with a lesser focus in the pediatric age group. We aim to outline the various pediatric ocular manifestations described in the literature. The manifestations may be divided into isolated events attributed to COVID-19 or occurring in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 infection. Ocular manifestations have virtually affected all ages. They manifested in neonates, infants, children, and adolescents. Episcleritis, conjunctivitis, optic neuritis, cranial nerve palsies, retinal vein occlusion, retinal vasculitis, retinal changes, orbital myositis, orbital cellulitis were reported in the literature with this emerging viral illness. Conjunctivitis was the most common ocular manifestation in MIS-C in nearly half of the patients. Other ocular manifestations in MIS-C were anterior uveitis, corneal epitheliopathy, optic neuritis, idiopathic intracranial hypertension, and retinitis. The clinical outcome was favorable, and children regain their visual ability with minimal or no deficits in most of the cases. Further follow-up may be warranted to better understand the long-term effects and visual prognosis.},
	keywords = {Adolescent, Adult, Child, Conjunctivitis, COVID-19, Humans, Infant, Infant, Newborn, Optic Neuritis, Retinitis},
	issn = {1724-6016},
	doi = {10.1177/11206721221116210},
	author = {Alnahdi, Muhannad A and Alkharashi, Maan}
}
@article {469016,
	title = {Differential Dimerization of Variants Linked to Enhanced S-Cone Sensitivity Syndrome (ESCS) Located in the NR2E3 Ligand-Binding Domain.},
	journal = {Hum Mutat},
	volume = {36},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {599-610},
	abstract = {NR2E3 encodes the photoreceptor-specific nuclear hormone receptor that acts as a repressor of cone-specific gene expression in rod photoreceptors, and as an activator of several rod-specific genes. Recessive variants located in the ligand-binding domain (LBD) of NR2E3 cause enhanced short wavelength sensitive- (S-) cone syndrome (ESCS), a retinal degeneration characterized by an excess of S-cones and non-functional rods. We analyzed the dimerization properties of NR2E3 and the effect of disease-causing LBD missense variants by bioluminescence resonance energy transfer (BRET(2) ) protein interaction assays. Homodimerization was not affected in presence of p.A256V, p.R039G, p.R311Q, and p.R334G variants, but abolished in presence of p.L263P, p.L336P, p.L353V, p.R385P, and p.M407K variants. Homology modeling predicted structural changes induced by NR2E3 LBD variants. NR2E3 LBD variants did not affect interaction with CRX, but with NRL and rev-erbα/NR1D1. CRX and NRL heterodimerized more efficiently together, than did either with NR2E3. NR2E3 did not heterodimerize with TLX/NR2E1 and RXRα/NR2C1. The identification of a new compound heterozygous patient with detectable rod function, who expressed solely the p.A256V variant protein, suggests a correlation between LBD variants able to form functional NR2E3 dimers and atypical mild forms of ESCS with residual rod function.},
	issn = {1098-1004},
	doi = {10.1002/humu.22775},
	author = {von Alpen, D{\'e}sir{\'e}e and Tran, Hoai Viet and Guex, Nicolas and Venturini, Giulia and Munier, Francis L and Schorderet, Daniel F and Haider, Neena B and Escher, Pascal}
}
@article {1806576,
	title = {Comment on "Prevalence and Economic Burden of Keratoconus in the United States"},
	journal = {Am J Ophthalmol},
	year = {2024},
	month = {2024 Feb 01},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2024.01.031},
	author = {Altamirano-Lamarque, Francisco and Oke, Isdin}
}
@article {1798401,
	title = {Association of Neighborhood Opportunity With Severity of Retinoblastoma at Presentation},
	journal = {Am J Ophthalmol},
	volume = {261},
	year = {2024},
	month = {2024 Jan 15},
	pages = {1-6},
	abstract = {PURPOSE: To examine the relationship between the Child Opportunity Index (COI) and severity of retinoblastoma at presentation.

DESIGN: Cross-sectional study.

METHODS: Children (age \&lt;18 years) treated for retinoblastoma at a tertiary care center between January 2000 and May 2023 were included. Residential census tract was used to determine the overall and domain-specific COI score for each child. Collected variables included age, sex, race/ethnicity, insurance type, and the International Classification of Retinoblastoma (ICRB) Group at initial examination. The primary outcome was Group D or E retinoblastoma at presentation. Mixed effects regression models were used to estimate the association of COI scores with disease severity at presentation.

RESULTS: This study included 125 children (51.2\% male). Median age at diagnosis was 13 months (IQR, 5-24 months). One hundred nine (87.2\%) children presented with Group D or E retinoblastoma and 33 (26.4\%) resided in low or very low opportunity neighborhoods. Children residing in neighborhoods with low overall COI scores (OR, 1.62; 95\% CI, 1.01-2.58; P = .044) and low education COI scores (OR, 1.77; 95\% CI, 1.13-2.79; P = .013) were at increased odds of presenting with ICRB Group D or E retinoblastoma after adjusting for individual-level socioeconomic factors.

CONCLUSION: Children residing in low opportunity neighborhoods-particularly low education opportunity-more often presented with advanced stage retinoblastoma than children residing in neighborhoods with higher opportunity scores. Efforts to improve preventative vision care and access to eye specialty care for children residing in low-resource areas are needed to reduce existing disparities in retinoblastoma.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2024.01.013},
	author = {Altamirano-Lamarque, Francisco and Lim, Caleb and Shah, Ankoor S and VanderVeen, Deborah K and Gonzalez, Efren and Oke, Isdin}
}
@article {669291,
	title = {Facial Emotion Recognition in Bipolar Disorder and Healthy Aging.},
	journal = {J Nerv Ment Dis},
	volume = {204},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {188-93},
	abstract = {Emotional face recognition is impaired in bipolar disorder, but it is not clear whether this is specific for the illness. Here, we investigated how aging and bipolar disorder influence dynamic emotional face recognition. Twenty older adults, 16 bipolar patients, and 20 control subjects performed a dynamic affective facial recognition task and a subsequent rating task. Participants pressed a key as soon as they were able to discriminate whether the neutral face was assuming a happy or angry facial expression and then rated the intensity of each facial expression. Results showed that older adults recognized happy expressions faster, whereas bipolar patients recognized angry expressions faster. Furthermore, both groups rated emotional faces more intensely than did the control subjects. This study is one of the first to compare how aging and clinical conditions influence emotional facial recognition and underlines the need to consider the role of specific and common factors in emotional face recognition.},
	issn = {1539-736X},
	doi = {10.1097/NMD.0000000000000453},
	author = {Altamura, Mario and Padalino, Flavia A and Stella, Eleonora and Balzotti, Angela and Bellomo, Antonello and Palumbo, Rocco and Di Domenico, Alberto and Mammarella, Nicola and Fairfield, Beth}
}
@article {1078706,
	title = {Multifocal ERG Responses in Subjects With a History of Preterm Birth},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {5},
	year = {2017},
	month = {2017 May 01},
	pages = {2603-2608},
	abstract = {Purpose: The purpose of this study is to assess cone-mediated central retinal function in children with a history of preterm birth, including subjects with and without retinopathy of prematurity (ROP). The multifocal electroretinogram (mfERG) records activity of the postreceptor retinal circuitry. Methods: mfERG responses were recorded to an array of 103 hexagonal elements that subtended 43{\textdegree} around a central fixation target. The amplitude and latency of the first negative (N1) and first positive (P1) response were evaluated in six concentric rings centered on the fovea. Responses were recorded from 40 subjects with a history of preterm birth (severe ROP, mild ROP, no ROP) and 19 term-born control subjects. Results: The amplitude of N1 and P1 varied significantly with eccentricity and ROP severity. For all four groups, these amplitudes were largest in the center and decreased with eccentricity. At all eccentricities, N1 amplitude was significantly smaller in severe ROP and did not differ significantly among the other three groups (mild ROP, no ROP, term-born controls). P1 amplitude in all preterm groups was significantly smaller than in controls; P1 amplitude was similar in no ROP and mild ROP and significantly smaller in severe ROP. Conclusions: These results provide evidence that premature birth alone affects cone-mediated central retinal function and that the magnitude of the effect varies with severity of the antecedent ROP. The lack of difference in mfERG amplitude between the mild and no ROP groups is evidence that the effect of ROP on the neurosensory retina may not depend solely on appearance of abnormal retinal vasculature.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-21587},
	author = {Altschwager, Pablo and Moskowitz, Anne and Fulton, Anne B and Hansen, Ronald M}
}
@article {1635658,
	title = {Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration},
	journal = {Elife},
	volume = {11},
	year = {2022},
	month = {2022 Mar 22},
	abstract = {Retinitis Pigmentosa (RP) is a progressive, debilitating visual disorder caused by mutations in a diverse set of genes. In both humans with RP and mouse models of RP, rod photoreceptor dysfunction leads to loss of night vision, and is followed by secondary cone photoreceptor dysfunction and degeneration, leading to loss of daylight color vision. A strategy to prevent secondary cone death could provide a general RP therapy to preserve daylight color vision regardless of the underlying mutation. In mouse models of RP, cones in the peripheral retina survive long-term, despite complete rod loss. The mechanism for such peripheral cone survival had not been explored. Here, we found that active retinoic acid (RA) signaling in peripheral Muller glia is necessary for the abnormally long survival of these peripheral cones. RA depletion by conditional knockout of RA synthesis enzymes, or overexpression of an RA degradation enzyme, abrogated the extended survival of peripheral cones. Conversely, constitutive activation of RA signaling in the central retina promoted long-term cone survival. These results indicate that RA signaling mediates the prolonged peripheral cone survival in the rd1 mouse model of retinal degeneration, and provide a basis for a generic strategy for cone survival in the many diseases that lead to loss of cone-mediated vision.},
	issn = {2050-084X},
	doi = {10.7554/eLife.76389},
	author = {Ryoji Amamoto and Wallick, Grace K and Cepko, Constance L}
}
@article {1474194,
	title = {FIN-Seq: transcriptional profiling of specific cell types from frozen archived tissue of the human central nervous system},
	journal = {Nucleic Acids Res},
	volume = {48},
	number = {1},
	year = {2020},
	month = {2020 Jan 10},
	pages = {e4},
	abstract = {Thousands of frozen, archived tissue samples from the human central nervous system (CNS) are currently available in brain banks. As recent developments in RNA sequencing technologies are beginning to elucidate the cellular diversity present within the human CNS, it is becoming clear that an understanding of this diversity would greatly benefit from deeper transcriptional analyses. Single cell and single nucleus RNA profiling provide one avenue to decipher this heterogeneity. An alternative, complementary approach is to profile isolated, pre-defined cell types and use methods that can be applied to many archived human tissue samples that have been stored long-term. Here, we developed FIN-Seq (Frozen Immunolabeled Nuclei Sequencing), a method that accomplishes these goals. FIN-Seq uses immunohistochemical isolation of nuclei of specific cell types from frozen human tissue, followed by bulk RNA-Sequencing. We applied this method to frozen postmortem samples of human cerebral cortex and retina and were able to identify transcripts, including low abundance transcripts, in specific cell types.},
	issn = {1362-4962},
	doi = {10.1093/nar/gkz968},
	author = {Ryoji Amamoto and Zuccaro, Emanuela and Curry, Nathan C and Khurana, Sonia and Chen, Hsu-Hsin and Cepko, Constance L and Arlotta, Paola}
}
@article {1478340,
	title = {Probe-Seq enables transcriptional profiling of specific cell types from heterogeneous tissue by RNA-based isolation},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 12 09},
	abstract = {Recent transcriptional profiling technologies are uncovering previously-undefined cell populations and molecular markers at an unprecedented pace. While single cell RNA (scRNA) sequencing is an attractive approach for unbiased transcriptional profiling of all cell types, a complementary method to isolate and sequence specific cell populations from heterogeneous tissue remains challenging. Here, we developed Probe-Seq, which allows deep transcriptional profiling of specific cell types isolated using RNA as the defining feature. Dissociated cells are labeled using fluorescent in situ hybridization (FISH) for RNA, and then isolated by fluorescent activated cell sorting (FACS). We used Probe-Seq to purify and profile specific cell types from mouse, human, and chick retinas, as well as from midguts. Probe-Seq is compatible with frozen nuclei, making cell types within archival tissue immediately accessible. As it can be multiplexed, combinations of markers can be used to create specificity. Multiplexing also allows for the isolation of multiple cell types from one cell preparation. Probe-Seq should enable RNA profiling of specific cell types from any organism.},
	issn = {2050-084X},
	doi = {10.7554/eLife.51452},
	author = {Ryoji Amamoto and Garcia, Mauricio D and West, Emma R and Choi, Jiho and Lapan, Sylvain W and Lane, Elizabeth A and Perrimon, Norbert and Cepko, Constance L}
}
@article {1137866,
	title = {Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {10},
	year = {2017},
	month = {2017 Aug 01},
	pages = {3940-3949},
	abstract = {Purpose: The purpose of this study was to develop a method for isolating, culturing, and characterizing cells from patient-derived membranes in proliferative vitreoretinopathy (PVR) to be used for drug testing. Methods: PVR membranes were obtained from six patients with grade C PVR. Membrane fragments were analyzed by gross evaluation, fixed for immunohistologic studies to establish cell identity, or digested with collagenase II to obtain single cell suspensions for culture. PVR-derived primary cultures were used to examine the effects of methotrexate (MTX) on proliferation, migration, and cell death. Results: Gross analysis of PVR membranes showed presence of pigmented cells, indicative of retinal pigment epithelial cells. Immunohistochemistry identified cells expressing α-smooth muscle actin, glial fibrillary acidic protein, Bestrophin-1, and F4/80, suggesting the presence of multiple cell types in PVR. Robust PVR primary cultures (C-PVR) were successfully obtained from human membranes, and these cells retained the expression of cell identity markers in culture. C-PVR cultures formed membranes and band-like structures in culture reminiscent of the human condition. MTX significantly reduced the proliferation and band formation of C-PVR, whereas it had no significant effect on cell migration. MTX also induced regulated cell death within C-PVR as assessed by increased expression of caspase-3/7. Conclusions: PVR cells obtained from human membranes can be successfully isolated, cultured, and profiled in vitro. Using these primary cultures, we identified MTX as capable of significantly reducing growth and inducing cell death of PVR cells in vitro.},
	keywords = {Adult, Aged, Apoptosis, Biomarkers, Cell Culture Techniques, Cell Movement, Cell Proliferation, Cell Separation, Epiretinal Membrane, Extracellular Matrix Proteins, Female, Fluorescent Antibody Technique, Indirect, Humans, Immunosuppressive Agents, Male, Methotrexate, Middle Aged, Models, Biological, Phenotype, Retinal Detachment, Retinal Pigment Epithelium, Tumor Necrosis Factor-alpha, Vitreoretinopathy, Proliferative},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20912},
	author = {Amarnani, Dhanesh and Machuca-Parra, Arturo Israel and Wong, Lindsay L and Marko, Christina K and Stefater, James A and Stryjewski, Tomasz P and Eliott, Dean and Arboleda-Velasquez, Joseph F and Kim, Leo A}
}
@article {1732591,
	title = {Do the retinal abnormalities in X-linked juvenile retinoschisis include impaired phototransduction?},
	journal = {Exp Eye Res},
	volume = {234},
	year = {2023},
	month = {2023 Sep},
	pages = {109591},
	abstract = {X-linked juvenile retinoschisis (XLRS), a hereditary retinal disorder primarily affecting males, is characterized by the formation of cystic spaces between the outer plexiform layer and outer nuclear layer of the retina. Mutations in the RS1 gene, which encodes the extracellular binding protein retinoschisin, are responsible for XLRS pathogenesis. While the role of retinoschisin in maintaining retinal integrity is well established, there is growing evidence suggesting compromised photoreceptor function in XLRS. To investigate the molecular pathways affected by RS1 deficiency, particularly in phototransduction, we performed electroretinographic (ERG) and proteomic analyses on retinae from Rs1 knockout mice, a model of human XLRS. The Rs1 knockout mice had reduced ERG a-wave amplitudes. Correspondingly, differential expression analysis revealed downregulation of proteins crucial for phototransduction, with Ingenuity Pathway Analysis (IPA) highlighting "phototransduction" as the most significantly downregulated biological theme. Compensatory mechanisms were also observed in the IPA, including upregulation of synaptic remodeling, inflammation, cell adhesion, and G-protein signaling. These findings strongly implicate an underrecognized role of photoreceptor dysfunction in XLRS pathology. We speculate that entrapment of mutant retinoschisin protein within photoreceptor inner segments as well as disrupted reciprocal regulation between L-type voltage-gated calcium channels and retinoschisin contribute to the dysfunction in photoreceptors.},
	keywords = {Animals, Cell Adhesion Molecules, Eye Proteins, Humans, Male, Mice, Mice, Knockout, Proteomics, Retina, Retinoschisis},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2023.109591},
	author = {Ambrosio, Lucia and Akula, James D and Harman, Jarrod C and Arellano, Ivana A and Fulton, Anne B}
}
@article {1549021,
	title = {Carbonic anhydrase inhibition in X-linked retinoschisis: An eye on the photoreceptors},
	journal = {Exp Eye Res},
	volume = {202},
	year = {2021},
	month = {2021 Jan},
	pages = {108344},
	abstract = {The retinoschisin protein is encoded on the short arm of the X-chromosome by RS1, is expressed abundantly in photoreceptor inner segments and in bipolar cells, and is secreted as an octamer that maintains the structural integrity of the retina. Mutations in RS1 lead to X-linked retinoschisis (XLRS), a disease characterized by the formation of cystic spaces between boys{\textquoteright} retinal layers that frequently present in ophthalmoscopy as a "spoke-wheel" pattern on their maculae and by progressively worsening visual acuity (VA). There is no proven therapy for XLRS, but there is mixed evidence that carbonic anhydrase inhibitors (CAIs) produce multiple beneficial effects, including improved VA and decreased volume of cystic spaces. Consequently, linear mixed-effects (LME) models were used to evaluate the effects of CAI therapy on VA and central retinal thickness (CRT, a proxy for cystic cavity volume) in a review of 19 patients{\textquoteright} records. The mechanism of action of action of CAIs is unclear but, given that misplaced retinoschisin might accumulate in the photoreceptors, it is possible-perhaps even likely-that CAIs act to benefit the function of photoreceptors and the neighboring retinal pigment epithelium by acidification of the extracellular milieu; patients on CAIs have among the most robust photoreceptor responses. Therefore, a small subset of five subjects were recruited for imaging on a custom multimodal adaptive optics retinal imager for inspection of their parafoveal cone photoreceptors. Those cones that were visible, which numbered far fewer than in controls, were enlarged, consistent with the retinoschisin accumulation hypothesis. Results of the LME modeling found that there is an initial benefit to both VA and CRT in CAI therapy, but these wane, in both cases, after roughly two years. That said, even a short beneficial effect of CAIs on the volume of the cystic spaces may give CAI therapy an important role as pretreatment before (or immediately following) administration of gene therapy.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.108344},
	author = {Ambrosio, Lucia and Williams, Jacqueline S and Gutierrez, Alfredo and Swanson, Emily A and Munro, Robert J and Ferguson, R Daniel and Fulton, Anne B and Akula, James D}
}
@article {1474192,
	title = {Retinal Function in X-Linked Juvenile Retinoschisis},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {14},
	year = {2019},
	month = {2019 Nov 01},
	pages = {4872-4881},
	abstract = {Purpose: To assess retinal function in young patients with X-linked juvenile retinoschisis (XLRS), a disorder that is known to alter ERG postreceptor retinal components and also possibly photoreceptor components. Methods: ERG responses to full-field stimuli were recorded under scotopic and photopic conditions in 12 XLRS patients aged 1 to 15 (median 8) years. A- and b-wave amplitudes and implicit times were examined over a range of stimulus intensities. Rod and cone photoreceptor (SROD, RROD, SCONE, RCONE) and rod-driven postreceptor (log σ, VMAX) response parameters were calculated from the a- and b-waves. Data from XLRS patients were evaluated for significant change with age. Results: A- and b-wave amplitudes were smaller in XLRS patients compared with controls under both scotopic and photopic conditions. Saturated photoresponse amplitude (RROD), postreceptor b-wave (log σ), and saturated b-wave amplitude (VMAX) were significantly lower in XLRS patients than in controls; SROD did not differ between the two groups. SCONE and RCONE values were normal. In XLRS patients, neither a- and b-wave amplitudes nor calculated parameters (SROD, RROD, log σ, VMAX,SCONE, and RCONE) changed with age. Conclusions: In these young XLRS patients, RROD and a-wave amplitudes were significantly smaller than in controls. Thus, in addition to XLRS causing postreceptor dysfunction, an effect of XLRS on rod photoreceptors cannot be ignored.},
	issn = {1552-5783},
	doi = {10.1167/iovs.19-27897},
	author = {Ambrosio, Lucia and Hansen, Ronald M and Kimia, Rotem and Fulton, Anne B}
}
@article {1573121,
	title = {Dark-adapted threshold and electroretinogram for diagnosis of Usher syndrome},
	journal = {Doc Ophthalmol},
	volume = {143},
	number = {1},
	year = {2021},
	month = {2021 Aug},
	pages = {39-51},
	abstract = {PURPOSE: To determine the utility of ophthalmology evaluation, dark-adapted threshold, and full-field electroretinogram for early detection of Usher syndrome in young patients with bilateral sensorineural hearing loss. METHODS: We identified 39 patients with secure genetic diagnoses of Usher Syndrome. Visual acuity, spherical equivalent, fundus appearance, dark-adapted threshold, and full-field electroretinogram results were summarized and compared to those in a group of healthy controls with normal hearing. In those Usher patients with repeated measures, regression analysis was done to evaluate for change in visual acuity and dark-adapted threshold with age. Spherical equivalent and full-field electroretinogram responses from dark- and light-adapted eyes were evaluated as a function of age. RESULTS: The majority of initial visual acuity and spherical equivalent results were within normal limits for age. Visual acuity and dark-adapted threshold worsened significantly with age in Usher type 1 but not in Usher type 2. At initial test, full-field electroretinogram responses from dark- and light-adapted eyes were abnormal in 53\% of patients. Remarkably, nearly half of our patients (17\% of Usher type 1 and 30\% of Usher type 2) would have been missed by tests of retinal function alone if evaluated before age 10. CONCLUSIONS: Although there is an association of abnormal dark-adapted threshold and full-field electroretinogram at young ages in Usher patients, it appears that a small but important proportion of patients would not be detected by tests of retinal function alone. Thus, genetic testing is needed to secure a diagnosis of Usher syndrome.},
	issn = {1573-2622},
	doi = {10.1007/s10633-021-09818-y},
	author = {Ambrosio, Lucia and Hansen, Ronald M and Moskowitz, Anne and Oza, Andrea and Barrett, Devon and Manganella, Juliana and Medina, Genevieve and Kawai, Kosuke and Fulton, Anne B and Kenna, Margaret}
}
@article {1598028,
	title = {Chemical Constituent, Antimicrobial Activity, and Synergistic Effect of the Stem, Leaf, and Flower Essential Oil of the Artemisia fragrans Willd. from Khoy},
	journal = {Chem Biodivers},
	volume = {18},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {e2100241},
	abstract = {Artemisia fragrans is commonly used as a folk medicine as antispasmodic, anti-pyretic, anti-inflammatory, and abortifacient agents. The villagers use its pungent odor to repel rodents, mites, and pests, as well as its essential oil and smoke after burning to treat lung infections after uprooting the plant. Herein, we extracted the essential oils (EOs) of different parts of the plant and analyzed their chemical compositions and antibacterial activities. The chemical analysis led to the identification of 73, 59, and 57 compounds in the EOs of the stem, leaf, and flower, respectively. All of the EOs exhibited antibacterial activities against both G+ and G- bacteria. The EOs of the leaf and flower were more effective against tested bacteria, except B. anthracis and P. aeruginosa, compared to that of the stem. The binary combination of the EOs (stem and flower) or (stem and leaf) showed a synergistic effect. Statistical analysis indicated EOs of leaf and flower are more potent than that of the stem. These findings suggest the application of leaf and flower of the plant, which not only can prevent its uprooting but also ensure better therapeutic function.},
	issn = {1612-1880},
	doi = {10.1002/cbdv.202100241},
	author = {Aminkhani, Ali and Sharifi, Sina and Hosseinzadeh, Pourya}
}
@article {1466906,
	title = {Chemical Composition and Antimicrobial Activity of Achillea tenuifolia Lam. Essential Oil at Different Phenological Stages from Khoy},
	journal = {Chem Biodivers},
	volume = {16},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {e1900289},
	abstract = {Achillea species and in particular Achillea tenuifolia Lam. is generally used as a food flavor and traditional remedies, especially in the initial developmental stage for medical conditions in the Mediterranean part of Iran. In this report, we extracted the essential oil from the aerial parts of A. tenuifolia (collected from Khoy), at various developmental stages (i. e., vegetative, flowering and fruiting), characterized them and studied their antibacterial activities. Of 46, 51 and 38 components found in the vegetative, flowering, and fruiting stages, respectively, 35 were present in all three stages, including oxygenated terpenes such as carvacrol (30.85-34.11), germacrene C (16.21-17.87), spathulenol (7.26-8.96), β-sesquiphellandrene (4.11-4.25), τ-muurolol (2.27-3.25) and α-cadinol (2.01-3.29). We witnessed that the composition of the essential oils varies with phenological stages and geographic regions. The essential oil demonstrated substantial antibacterial properties against both Gram-positive and Gram-negative bacteria, indicated by disk method, Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays. Except Pseudomonas aeruginosa, the essential oils of various phenological stages showed higher antibacterial activity against tested bacteria, with Bacillus anthracis as the most sensitive strain. Moreover, although antibacterial characteristics of the essential oil from the vegetative and flowering stages were similar (p=0.91), they were significantly different from those of fruiting stage (p\&lt;0.005 in both MIC and MBC tests). This emphasizes the importance of the developmental stage of the plant in the biological properties of its essential oil and justifies the widespread application of this plant in the vegetative stage.},
	issn = {1612-1880},
	doi = {10.1002/cbdv.201900289},
	author = {Aminkhani, Ali and Sharifi, Roholah and Dorosti, Reza}
}
@article {1504079,
	title = {Achillea filipendulina Lam.: Chemical Constituents and Antimicrobial Activities of Essential Oil of Stem, Leaf, and Flower},
	journal = {Chem Biodivers},
	volume = {17},
	number = {5},
	year = {2020},
	month = {2020 May},
	pages = {e2000133},
	abstract = {In this study, we extracted the essential oils of the stem, leaf, and flower of Achillea filipendulina, analyzed them, and studied their antibacterial properties. Of 16, 53, and 35 compounds identified in the stem, leaf, and flowers, respectively, only five are present in all three segments of the plant. The essential oil of the stem was mainly composed of neryl acetate, spathulenol, carvacrol, santolina alcohol, and trans-caryophyllene oxide. However, the main identified components of leaf were 1,8-cineole, camphor, ascaridole, trans-isoascaridole, and piperitone oxide and the main components of the flower oil were ascaridole, trans-isoascaridole, 1,8-cineole, p-cymene, and camphor. The extracted oil from different segments demonstrated varying antibacterial properties against both Gram-positive and Gram-negative bacteria, demonstrated by disk, minimum inhibitory concentration, and minimum bactericidal concentration methods. These suggest that the application of all segments of aerial parts of A. filipendulina may have a better therapeutic effect in fighting pathogenic systems.},
	issn = {1612-1880},
	doi = {10.1002/cbdv.202000133},
	author = {Aminkhani, Ali and Sharifi, Sina and Ekhtiyari, Shirin}
}
@article {1043186,
	title = {Mesenchymal Stem Cells Modulate Differentiation of Myeloid Progenitor Cells During Inflammation},
	journal = {Stem Cells},
	volume = {35},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {1532-1541},
	abstract = {Mesenchymal stem cells (MSCs) possess distinct immunomodulatory properties and have tremendous potential for use in therapeutic applications in various inflammatory diseases. MSCs have been shown to regulate pathogenic functions of mature myeloid inflammatory cells, such as macrophages and neutrophils. Intriguingly, the capacity of MSCs to modulate differentiation of myeloid progenitors (MPs) to mature inflammatory cells remains unknown to date. Here, we report the novel finding that MSCs inhibit the expression of differentiation markers on MPs under inflammatory conditions. We demonstrate that the inhibitory effect of MSCs is dependent on direct cell-cell contact and that this intercellular contact is mediated through interaction of CD200 expressed by MSCs and CD200R1 expressed by MPs. Furthermore, using an injury model of sterile inflammation, we show that MSCs promote MP frequencies and suppress infiltration of inflammatory cells in the inflamed tissue. We also find that downregulation of CD200 in MSCs correlates with abrogation of their immunoregulatory function. Collectively, our study provides unequivocal evidence that MSCs inhibit differentiation of MPs in the inflammatory environment via CD200-CD200R1 interaction. Stem Cells 2017;35:1532-1541.},
	issn = {1549-4918},
	doi = {10.1002/stem.2611},
	author = {Amouzegar, Afsaneh and Mittal, Sharad K and Sahu, Anuradha and Sahu, Srikant K and Chauhan, Sunil K}
}
@article {1363240,
	title = {The Ocular Redness Index: a novel automated method for measuring ocular injection},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {7},
	year = {2013},
	month = {2013 Jul 18},
	pages = {4821-6},
	abstract = {PURPOSE: To develop and validate a novel automated system to assess ocular redness (OR) in clinical images. METHODS: We developed a novel software that quantifies OR in digital images based on a mathematic algorithm using a centesimal continuous scoring scale. Subsequently, we conducted a study to validate the scores obtained with this system by correlating them with those obtained by two physicians using two image-based comparative subjective scales, the Efron and the Validated Bulbar Redness (VBR) grading scales. Additionally, we evaluated the level of clinical agreement between the Ocular Redness Index (ORI) score and the two image-based methods by means of the Bland-Altman analysis. Main outcome measures included correlation and level of agreement between the ORI score, Efron score, and the VBR score. RESULTS: One hundred and two clinical photographs of eyes with OR were evaluated. The ORI scores significantly correlated with the scores obtained by the two clinicians using the Efron (Observer 1, R=0.925, P\&lt;0.001; Observer 2, R=0.857, P\&lt;0.001), and VBR (Observer 1, R=0.830, P\&lt;0.001; Observer 2, R=0.821, P\&lt;0.001) scales. The Bland-Altman analysis revealed levels of disagreement of up to 30 and 27 units for the ORI-Efron and ORI-VBR score comparisons, respectively. CONCLUSIONS: The ORI provides an objective and continuous scale for evaluating ocular injection in an automated manner, and without need for a trained physician for scoring. The ORI may be used as a new alternative for objective OR evaluation in clinics and in clinical trials.},
	keywords = {Algorithms, Conjunctivitis, Diagnosis, Computer-Assisted, Humans, Observer Variation, Photography, Severity of Illness Index, Software},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12217},
	author = {Amparo, Francisco and Wang, Haobing and Emami-Naeini, Parisa and Karimian, Parisa and Dana, Reza}
}
@article {416906,
	title = {Comparison of Two Questionnaires for Dry Eye Symptom Assessment: The Ocular Surface Disease Index and the Symptom Assessment in Dry Eye.},
	journal = {Ophthalmology},
	volume = {122},
	number = {7},
	year = {2015},
	month = {2015 Jul},
	pages = {1498-503},
	abstract = {PURPOSE: The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) as assessed by the Ocular Surface Disease Index (OSDI), a 12-item symptom frequency-based questionnaire, and the Symptom Assessment iN Dry Eye (SANDE), a 2-item frequency- and severity-based visual analog scale. DESIGN: Clinic-based evaluation of a diagnostic test. PARTICIPANTS: A total of 114 patients with DED. METHODS: Patients were administered the OSDI and SANDE questionnaires at baseline and follow-up visits to evaluate DED-related symptoms. The correlations between both questionnaires{\textquoteright} scores were evaluated using the Spearman coefficient, and their clinical differences were assessed using Bland-Altman analysis. MAIN OUTCOME MEASURES: Baseline and follow-up visit OSDI and SANDE dry eye symptom scores. RESULTS: At the baseline visit, the OSDI and SANDE questionnaire scores were significantly correlated (R\&nbsp;=\&nbsp;0.64; P \&lt; 0.001). Moreover, a significant correlation was found between changes in the OSDI and SANDE scores from baseline to follow-up visits (R\&nbsp;= 0.47; P \&lt; 0.001). A Bland-Altman analysis, after score normalization, revealed a difference (bias) of less than 2 centesimal units between the scores of the 2 questionnaires. CONCLUSIONS: Data collected from the SANDE questionnaire showed a significant correlation and negligible score\&nbsp;differences with those from the OSDI, suggesting that the SANDE visual analog scale-based questionnaire has\&nbsp;the potential to provide clinicians with a short, quick, and reliable measure for DED symptoms.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.02.037},
	author = {Amparo, Francisco and Schaumberg, Debra A and Dana, Reza}
}
@article {1363241,
	title = {Safety and efficacy of the multitargeted receptor kinase inhibitor pazopanib in the treatment of corneal neovascularization},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {1},
	year = {2013},
	month = {2013 Jan 17},
	pages = {537-44},
	abstract = {PURPOSE: To evaluate the safety and efficacy of topical pazopanib in the treatment of corneal neovascularization (CNV). METHODS: Twenty eyes of 20 patients with stable CNV were enrolled in a prospective, open label, noncomparative study and treated with topical pazopanib 0.5\% for 3 weeks, and followed for 12 weeks. The primary endpoint was to determine the tolerability and safety of topical pazopanib in the treatment of CNV defined by the occurrence of ocular and systemic adverse events during the study. The secondary endpoint was to evaluate the effect of topical pazopanib on the reduction of (1) neovascular area (NA), defined as the area of the corneal vessels themselves, (2) invasion area (IA), defined as the fraction of the total cornea into which the vessels extend, (3) vessel length (VL), defined as the mean measurement of the extent of vessels from end to end, and (4) vessel caliber (VC), defined as the mean diameter of the corneal vessels. RESULTS: There were no severe adverse events following the use of topical pazopanib. Compared with the baseline visit, NA and VL showed a statistically significant decrease at week 3 (P = 0.02 and 0.01, respectively); and NA, IA, and VL statistically significantly decreased at week 12 (P = 0.03, 0.04, and \&lt;0.01, respectively). Visual acuity maintained without changes after the 12 week follow-up. CONCLUSIONS: This preliminary study suggests that topical treatment with pazopanib 0.5\% is safe, well tolerated, and may have a role as an alternative for the treatment of CNV (ClinicalTrials.gov number, NCT01257750).},
	keywords = {Adult, Aged, Angiogenesis Inhibitors, Corneal Neovascularization, Female, Follow-Up Studies, Humans, Male, Middle Aged, Ophthalmic Solutions, Prospective Studies, Pyrimidines, Receptors, Vascular Endothelial Growth Factor, Sulfonamides, Treatment Outcome, Young Adult},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-11032},
	author = {Amparo, Francisco and Sadrai, Zahra and Jin, Yiping and Alfonso-Bartolozzi, Belen and Wang, Haobing and Shikari, Hasanain and Ciolino, Joseph B and Chodosh, James and Jurkunas, Ula and Schaumberg, Debra A and Dana, Reza}
}
@article {1318854,
	title = {Corneal fluorescein staining and ocular symptoms but not Schirmer test are useful as indicators of response to treatment in chronic ocular GVHD},
	journal = {Ocul Surf},
	volume = {16},
	number = {3},
	year = {2018},
	month = {2018 Jul},
	pages = {377-381},
	abstract = {PURPOSE: To evaluate long-term ocular surface clinical signs and symptoms response to therapy in patients with chronic ocular GVHD. METHODS: Retrospective review and data modeling. We reviewed the records of post-bone marrow transplantation patients who were newly diagnosed with ocular GVHD and initiated therapy, and analyzed changes in symptoms (Ocular Surface Disease Index [OSDI]; Symptom Assessment in Dry Eye [SANDE]) and signs (corneal fluorescein staining [CFS]; Schirmer test). We used a LOESS technique to fit a model in function of data variations and obtain a predictive value of the scores progression over time. RESULTS: The records of 123 patients who were followed-up for over 2 years (up to 62 months) were reviewed. The median baseline scores recorded were: OSDI 52 units, SANDE 62.2 units, CFS 2.0 Oxford units, and Schirmer 4 mm. After six months of follow up, scores improved for OSDI (-18.6 units, p = 0.007), SANDE (23.7 units, p = 0.01), and CFS (-0.7 Oxford units, p \&lt; 0.001). Data analysis showed that after a 2-year follow up the three parameters continued to improve: OSDI -13.67 units (27\% reduction), SANDE -17.55 units (28\%), CFS -1.1 units (54\%), but Schirmer test scores progressively worsened -1.2 mm (22\%). CONCLUSION: In patients with ocular GVHD symptoms and corneal fluorescein staining improved after initiation of treatment, meanwhile Schirmer scores declined progressively. This indicates that appropriate treatment in chronic ocular GVHD can lead to mid- and long-term improvements in symptoms and corneal epitheliopathy; however, sustained reduction in Schirmer test scores suggests chronic tear production impairment.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.05.002},
	author = {Amparo, Francisco and Shikari, Hasanain and Saboo, Ujwala and Dana, Reza}
}
@article {1309973,
	title = {Web-based longitudinal remote assessment of dry eye symptoms},
	journal = {Ocul Surf},
	volume = {16},
	number = {2},
	year = {2018},
	month = {2018 Apr},
	pages = {249-253},
	abstract = {PURPOSE: To investigate the feasibility of remote assessment and follow-up of dry eye symptoms using electronic versions of two validated questionnaires. METHODS: We conducted a prospective study of consecutive patients with dry eye disease (DED). Patients were enrolled during a clinical visit and were explained how to respond electronic versions of the Ocular surface Disease Index (OSDI) and the Symptom Assessment in Dry Eye (SANDE) questionnaires using a computer in the presence of investigators. A secure link to both questionnaires was sent to each patient every 2 weeks in order to respond and submit their symptoms over a 3-month period. We analyzed the number of patients who responded to both questionnaires, the recurrence, and the symptoms scores reported. RESULTS: A total of 1121 questionnaires were collected; 103 patients (85\%) reported their symptoms at least once during the 3-month study duration. The majority of participants who completed the study (71.6\%) responded remotely at least once per month during the 3-month duration of the study. The mean OSDI and SANDE scores from the total of remote evaluations were 34.9 {\textpm} 21.9 (range 0-97.5) and 50.3 {\textpm} 24.9 (range 0-100), respectively. There was a statistically significant correlation between the total scores collected with the two questionnaires (R = 0.67, P \&lt; 0.001). CONCLUSIONS: Patients are motivated to report DED symptoms while away from the clinic. Distance-based evaluation of DED symptoms is both feasible and convenient, and can be implemented to follow symptoms in large populations with chronic dry eye.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.01.002},
	author = {Amparo, Francisco and Dana, Reza}
}
@article {1125256,
	title = {Evaluating Changes in Ocular Redness Using a Novel Automated Method},
	journal = {Transl Vis Sci Technol},
	volume = {6},
	number = {4},
	year = {2017},
	month = {2017 Jul},
	pages = {13},
	abstract = {PURPOSE: To evaluate interobserver concordance in measured ocular redness among a group of raters using an objective computer-assisted method (ocular redness index [ORI]) and a group of clinicians using an ordinal comparative scale. METHODS: We conducted a prospective study to evaluate ocular redness in clinical photographs of 12 patients undergoing pterygium surgery. Photographs were acquired preoperatively, and at 1 week and 1 month postoperatively. One group of clinicians graded conjunctival redness in the photographs using an image-based comparative scale. A second group applied the ORI to measure redness in the same photographs. We evaluated redness change between time points, level of agreement among raters, and assessed redness score differences among observers within each group. RESULTS: Interobserver agreement using the image-based redness scale was 0.458 (P \&lt; 0.001). Interobserver agreement with the ORI was 0.997 (P \&lt; 0.001). We observed statistically significant differences among clinicians{\textquoteright} measurements obtained with the image-based redness scale (P \&lt; 0.001). There were no significant differences among measurements obtained with the ORI (P = 0.27). We observed a significant change in redness between baseline and follow-up visits with all scoring methods. Detailed analysis of redness change was performed only in the ORI group due to availability of continuous scores. CONCLUSION: Our findings suggest that the ORI scores provide higher consistency among raters than ordinal scales, and can discriminate redness changes that clinical observers often can miss. TRANSLATIONAL RELEVANCE: The ORI may be a reliable alternative to measure ocular redness objectively in the clinic and in clinical trials.},
	issn = {2164-2591},
	doi = {10.1167/tvst.6.4.13},
	author = {Amparo, Francisco and Yin, Jia and Di Zazzo, Antonio and Abud, Tulio and Jurkunas, Ula V and Hamrah, Pedram and Dana, Reza}
}
@article {1363239,
	title = {Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial},
	journal = {JAMA Ophthalmol},
	volume = {131},
	number = {6},
	year = {2013},
	month = {2013 Jun},
	pages = {715-723},
	abstract = {IMPORTANCE: The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. OBJECTIVE: To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. DESIGN AND SETTING: Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. PARTICIPANTS: Seventy-five patients with refractory DED. INTERVENTIONS: Participants were randomized to receive treatment with topical anakinra, 2.5\% (n = 30), anakinra, 5\% (n = 15), or vehicle (1\% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks. MAIN OUTCOMES AND MEASURES: Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. RESULTS: Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5\%, achieved a 46\% reduction in their mean CFS score (P = .12 compared with vehicle and P \&lt; .001 compared with baseline); participants treated with anakinra, 5\%, achieved a 17\% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19\% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29\%) treated with anakinra, 2.5\%, vs in 2 of 29 patients (7\%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5\%, and treatment with anakinra, 5\%, led to significant reductions in symptoms of 30\% and 35\%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5\% reduction in symptoms. CONCLUSIONS AND RELEVANCE: Treatment with topical anakinra, 2.5\%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681109.},
	keywords = {Administration, Ophthalmic, Adult, Aged, Boston, Chi-Square Distribution, Diagnostic Techniques, Ophthalmological, Double-Blind Method, Dry Eye Syndromes, Female, Fluorescein, Fluorescent Dyes, Humans, Immunologic Factors, Interleukin 1 Receptor Antagonist Protein, Male, Meibomian Glands, Middle Aged, Ophthalmic Solutions, Predictive Value of Tests, Prospective Studies, Time Factors, Treatment Outcome},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.195},
	author = {Amparo, Francisco and Dastjerdi, Mohammad H and Okanobo, Andre and Ferrari, Giulio and Smaga, Leila and Hamrah, Pedram and Jurkunas, Ula and Schaumberg, Debra A and Dana, Reza}
}
@article {1351133,
	title = {What is the value of incorporating tear osmolarity measurement in assessing patient response to therapy in dry eye disease?},
	journal = {Am J Ophthalmol},
	volume = {157},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {69-77.e2},
	abstract = {PURPOSE: To evaluate the correlation between changes in tear osmolarity, symptoms, and corneal fluorescein staining in patients with dry eye disease (DED).

DESIGN: Retrospective, clinic-based cohort study.

METHODS: In this single-institution study, we reviewed the charts of 186 patients with DED from whom we had data on tear osmolarity, symptoms, and corneal fluorescein staining from 2 separate visits. Main outcomes included the correlation of the changes between the 2 visits for tear osmolarity (TearLab system), symptoms (Ocular Surface Disease Index), and corneal fluorescein staining (modified Oxford scheme). For tear osmolarity and corneal fluorescein staining the scores from the eye with highest readings were analyzed. The correlations were repeated on subgroups based on proposed cutoffs for DED severity and on patients{\textquoteright} treatment.

RESULTS: We found a modest, though statistically significant, correlation between changes in corneal fluorescein staining and symptoms of DED (R = 0.31; P < .001). However, there was no correlation between the recorded change in tear osmolarity and symptoms (R = -0.091; P = .38) or between changes in tear osmolarity and corneal fluorescein staining (R = -0.02; P = .80). This lack of correlation was consistent in all the subgroups studied. A multivariate analysis revealed that changes in corneal fluorescein staining had predictive value on symptom changes, whereas tear osmolarity changes did not.

CONCLUSIONS: Changes in tear osmolarity do not correlate significantly with changes in patient symptoms or corneal fluorescein staining in dry eye disease.},
	keywords = {Antirheumatic Agents, Blood, Cornea, Cyclosporine, Dry Eye Syndromes, Female, Fluorescein, Fluorescent Dyes, Fluorophotometry, Glucocorticoids, Humans, Immunosuppressive Agents, Interleukin 1 Receptor Antagonist Protein, Lubricants, Male, Middle Aged, Ophthalmic Solutions, Osmolar Concentration, Retrospective Studies, Surveys and Questionnaires, Tears},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.07.019},
	author = {Amparo, Francisco and Jin, Yiping and Hamrah, Pedram and Schaumberg, Debra A and Dana, Reza}
}
@article {1062806,
	title = {Endogenous Cryptococcal Endophthalmitis in Immunocompetent Host: Case Report and Review of Multimodal Imaging Findings and Treatment},
	journal = {Ocul Immunol Inflamm},
	year = {2017},
	month = {2017 Apr 27},
	pages = {1-5},
	abstract = {PURPOSE: To describe a case of bilateral endogenous cryptococcal endophthalmitis in an immunocompetent host and to review adjunctive ophthalmic imaging patterns and treatment. METHODS: A retrospective case report. RESULTS: A 45-year-old female patient with two distinct presentations of endogenous cryptococcal endophthalmitis in each eye presented initially with progressive blurred vision in the left eye, beginning more than 10 years after a craniotomy with ventriculoperitoneal shunt. Complete ophthalmic imaging was conducted and compared with data from previous literature. Administration of amphotericin-B had poorly responded; however, consolidation of fluconazole resulted in disease stabilization. CONCLUSIONS: Bilateral intraocular cryptococcal infection can present with two distinct patterns of posterior segment findings. A review of ophthalmic imaging patterns found consistency in some characteristics of A-scan ultrasonogram and fundus fluorescein angiogram. Besides conventional treatment, voriconazole is likely to play an important role in the management of cryptococcal endophthalmitis.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2017.1298820},
	author = {Amphornphruet, Atchara and Silpa-Archa, Sukhum and Preble, Janine M and Foster, C Stephen}
}
@article {1445346,
	title = {Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Jun 03},
	abstract = {In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial motor neurons (CrMN) are spared until late stages of the disease. Using a rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) to SpMNs and CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 and insoluble p62 than SpMNs over time. ESC-derived CrMNs have higher proteasome activity to degrade misfolded proteins and are intrinsically more resistant to chemically-induced proteostatic stress than SpMNs. Chemical and genetic activation of the proteasome rescues SpMN sensitivity to proteostatic stress. In agreement, the hSOD1 G93A mouse model reveals that ALS-resistant CrMNs accumulate less insoluble hSOD1 and p62-containing inclusions than SpMNs. Primary-derived ALS-resistant CrMNs are also more resistant than SpMNs to proteostatic stress. Thus, an ESC-based platform has identified a superior capacity to maintain a healthy proteome as a possible mechanism to resist ALS-induced neurodegeneration.},
	issn = {2050-084X},
	doi = {10.7554/eLife.44423},
	author = {An, Disi and Fujiki, Ryosuke and Iannitelli, Dylan E and Smerdon, John W and Maity, Shuvadeep and Rose, Matthew F and Gelber, Alon and Wanaselja, Elizabeth K and Yagudayeva, Ilona and Lee, Joun Y and Vogel, Christine and Wichterle, Hynek and Engle, Elizabeth C and Mazzoni, Esteban Orlando}
}
@article {1798391,
	title = {Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo},
	journal = {Nat Biotechnol},
	year = {2024},
	month = {2024 Jan 08},
	abstract = {Prime editing enables precise installation of genomic substitutions, insertions and deletions in living systems. Efficient in vitro and in vivo delivery of prime editing components, however, remains a challenge. Here we report prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. We systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to a PE-eVLP construct based on our previously reported base editor eVLP architecture. In two mouse models of genetic blindness, single injections of v3 PE-eVLPs resulted in therapeutically relevant levels of prime editing in the retina, protein expression restoration and partial visual function rescue. Optimized PE-eVLPs support transient in vivo delivery of prime editor ribonucleoproteins, enhancing the potential safety of prime editing by reducing off-target editing and obviating the possibility of oncogenic transgene integration.},
	issn = {1546-1696},
	doi = {10.1038/s41587-023-02078-y},
	author = {An, Meirui and Raguram, Aditya and Du, Samuel W and Banskota, Samagya and Davis, Jessie R and Newby, Gregory A and Chen, Paul Z and Palczewski, Krzysztof and Liu, David R}
}
@article {1474187,
	title = {Inflammatory Disorders of the Skull Base: a Review},
	journal = {Curr Neurol Neurosci Rep},
	volume = {19},
	number = {12},
	year = {2019},
	month = {2019 Nov 26},
	pages = {96},
	abstract = {PURPOSE OF REVIEW: In recent years, literature on neuroinflammatory disorders has dramatically expanded, as have options for treatment. However, few reviews have focused on skull-based manifestations of inflammatory disorders. RECENT FINDINGS: Here, we review the clinical manifestations, etiologies, diagnostic workup, and treatment of both systemic and localized inflammatory diseases of the skull base with a focus on recent updates to the literature. This review aims to guide the workup and management of this complex set of diseases.},
	issn = {1534-6293},
	doi = {10.1007/s11910-019-1016-x},
	author = {Anand, Pria and Chwalisz, Bart K}
}
@article {1532341,
	title = {A Review of Cyclodestructive Procedures for the Treatment of Glaucoma},
	journal = {Semin Ophthalmol},
	year = {2020},
	month = {2020 Sep 16},
	pages = {1-15},
	abstract = {Cyclodestruction aims to reduce aqueous humor production through the coagulation or destruction of the ciliary body and has been an important treatment choice for glaucoma since the 1930s. The purpose of the current review is to highlight the evidence regarding the safety and efficacy of various cyclodestructive modalities, emphasizing peer-reviewed articles from the last 20\&nbsp;years and the most common variants of these procedures. The review focuses primarily on the two most common variants of transscleral cyclophotocoagulation (TS-CPC), continuous-wave diode cyclophotocoagulation (CW-TSCPC) and MicroPulse diode cyclophotocoagulation (MP-TSCPC) as well as endoscopic cyclophotocoagulation (ECP) and high-intensity focused ultrasound cyclodestruction (HIFU). We believe that the role of cyclodestruction in glaucoma treatment will only continue to expand given the advances in the field, particular with regards to targeted ciliary body destruction and improvement in the safety profile.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1810711},
	author = {Anand, Nandita and Klug, Emma and Nirappel, Abraham and Sol{\'a}-Del Valle, David}
}
@article {1511505,
	title = {Severe vernal keratoconjunctivitis complicated by anaesthetic abuse},
	journal = {Can J Ophthalmol},
	year = {2020},
	month = {2020 May 24},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2020.04.020},
	author = {Anchouche, Sonia and Yin, Jia}
}
@article {1603871,
	title = {Chemical and thermal ocular burns in the United States: An IRIS registry analysis},
	journal = {Ocul Surf},
	volume = {21},
	year = {2021},
	month = {2021 Jul},
	pages = {345-347},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.03.008},
	author = {Anchouche, Sonia and Hall, Nathan and Bal, Sila and Dana, Reza and Tobias Elze and Miller, Joan W and Lorch, Alice C and Yin, Jia and IRIS Registry Data Analytic Centers}
}
@article {1798456,
	title = {Characterization of the resistome and predominant genetic lineages of Gram-positive bacteria causing keratitis},
	journal = {Antimicrob Agents Chemother},
	volume = {68},
	number = {3},
	year = {2024},
	month = {2024 Mar 06},
	pages = {e0124723},
	abstract = {Bacterial keratitis is a vision-threatening infection mainly caused by Gram-positive bacteria (GPB). Antimicrobial therapy is commonly empirical using broad-spectrum agents with efficacy increasingly compromised by the emergence of antimicrobial resistance. We used a combination of phenotypic tests and genome sequencing to identify the predominant lineages of GPB causing keratitis and to characterize their antimicrobial resistance patterns. A total of 161 isolates, including Staphylococcus aureus (n = 86), coagulase-negative staphylococci (CoNS; n = 34), Streptococcus spp. (n = 34), and Enterococcus faecalis (n = 7), were included. The population of S. aureus isolates consisted mainly of clonal complex 5 (CC5) (30.2\%). Similarly, the population of Staphylococcus epidermidis was homogenous with most of them belonging to CC2 (78.3\%). Conversely, the genetic population of Streptococcus pneumoniae was highly diverse. Resistance to first-line antibiotics was common among staphylococci, especially among CC5 S. aureus. Methicillin-resistant S. aureus was commonly resistant to fluoroquinolones and azithromycin (78.6\%) and tobramycin (57\%). One-third of the CoNS were resistant to fluoroquinolones and 53\% to azithromycin. Macrolide resistance was commonly caused by erm genes in S. aureus, mphC and msrA in CoNS, and mefA and msr(D) in streptococci. Aminoglycoside resistance in staphylococci was mainly associated with genes commonly found in mobile genetic elements and that encode for nucleotidyltransferases like ant(4{\textquoteright})-Ib and ant(9)-Ia. Fluroquinolone-resistant staphylococci carried from 1 to 4 quinolone resistance-determining region mutations, mainly in the gyrA and parC genes. We found that GPB causing keratitis are associated with strains commonly resistant to first-line topical therapies, especially staphylococcal isolates that are frequently multidrug-resistant and associated with major hospital-adapted epidemic lineages.},
	keywords = {Anti-Bacterial Agents, Anti-Infective Agents, Azithromycin, Drug Resistance, Bacterial, Fluoroquinolones, Humans, Macrolides, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Staphylococcal Infections, Staphylococcus, Staphylococcus aureus, Streptococcus},
	issn = {1098-6596},
	doi = {10.1128/aac.01247-23},
	author = {Andr{\'e}, Camille and Van Camp, Andrew G and Ung, Lawson and Gilmore, Michael S and Bispo, Paulo J M}
}
@article {1580478,
	title = {A Cluster of Corneal Donor Rim Cultures Positive for Achromobacter Species Associated With Contaminated Eye Solution},
	journal = {Cornea},
	volume = {40},
	number = {2},
	year = {2021},
	month = {2021 Feb 01},
	pages = {223-227},
	abstract = {PURPOSE: To investigate a cluster of corneoscleral rim cultures positive for Achromobacter species over a 6-month period at Massachusetts Eye and Ear. METHODS: An increased rate of positive corneal donor rim cultures was noted at Massachusetts Eye and Ear between July and December 2017. Positive cultures were subjected to identification and antimicrobial susceptibility testing by phenotypic (MicroScan WalkAway) and genotypic (16S rDNA sequencing) methods. Samples of the eye wash solution (GeriCare) used in the eye bank were also evaluated. Antimicrobial activity of Optical-GS against Achromobacter spp. at 4{\textdegree}C and 37{\textdegree}C was assessed by time-kill kinetics assay. RESULTS: Of 99 donor rims cultured, 14 (14.1\%) grew bacteria with 11 (78.6\%) due to uncommon nonfermenting Gram-negative bacilli. These had been identified by standard automated methods as Achromobacter (n = 3), Alcaligenes (n = 3), Ralstonia (n = 2), Pseudomonas (n = 2), and Stenotrophomonas (n = 1). Eight of these 11 isolates were subsequently available for molecular identification, and all were identified as Achromobacter spp. Six bottles of eyewash solution were evaluated and were positive for abundant Achromobacter spp. (3.4 {\texttimes} 105 {\textpm} 1.1 CFU/mL). Optisol-GS had no bactericidal activity against Achromobacter spp. at 4{\textdegree}C after 24-hour incubation but was bactericidal at 37{\textdegree}C. None of the patients who had received the contaminated corneas developed postoperative infection. CONCLUSIONS: An eyewash solution arising from a single lot was implicated in the contamination of donor rims by Achromobacter spp. The isolates were able to survive in the Optisol-GS medium at the recommended storage temperature. This highlights the need to continue improving protocols for tissue preparation and storage.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002473},
	author = {Andr{\'e}, Camille and Durand, Marlene L and Buckley, Thomas and Cadorette, James and Gilmore, Michael S and Ciolino, Joseph B and Bispo, Paulo J M}
}
@article {1635645,
	title = {Population structure of ocular Streptococcus pneumoniae is highly diverse and formed by lineages that escape current vaccines},
	journal = {Microb Genom},
	volume = {8},
	number = {3},
	year = {2022},
	month = {2022 Mar},
	abstract = {Streptococcus pneumoniae is a leading cause of ocular infections including serious and sight-threatening conditions. The use of pneumococcal conjugate vaccines (PCV) has substantially reduced the incidence of pneumonia and invasive pneumococcal diseases, but has had limited impact on ocular infections. Additionally, widespread vaccine use has resulted in ongoing selective pressure and serotype replacement in carriage and disease. To gain insight into the population structure of pneumococcal isolates causing ocular infections in a post-PCV-13 time period, we investigated the genomic epidemiology of ocular S. pneumoniae isolates (n=45) collected at Massachusetts Eye and Ear between 2014 and 2017. By performing a series of molecular typing methods from draft genomes, we found that the population structure of ocular S. pneumoniae is highly diverse with 27 sequence types (grouped into 18 clonal complexes) and 17 serotypes being identified. Distribution of these lineages diverged according to the site of isolation, with conjunctivitis being commonly caused by isolates grouped in the Epidemic Conjunctivitis Cluster-ECC (60 \%), and ST448 (53.3 \%) being most frequently identified. Conversely, S. pneumoniae keratitis cases were caused by a highly diverse population of isolates grouping within 15 different clonal complexes. Serotyping inference demonstrated that 95.5 \% of the isolates were non-PCV-13 vaccine types. Most of the conjunctivitis isolates (80 \%) were unencapsulated, with the remaining belonging to serotypes 15B, 3 and 23B. On the other hand, S. pneumoniae causing keratitis were predominantly encapsulated (95.2 \%) with 13 different serotypes identified, mostly being non-vaccine types. Carriage of macrolide resistance genes was common in our ocular S. pneumoniae population (42.2 \%), and usually associated with the mefA +msrD genotype (n=15). These genes were located in the Macrolide Efflux Genetic Assembly cassette and were associated with low-level in vitro resistance to 14- and 15-membered macrolides. Less frequently, macrolide-resistant isolates carried an ermB gene (n=4), which was co-located with the tetM gene in a Tn-916-like transposon. Our study demonstrates that the population structure of ocular S. pneumoniae is highly diverse, mainly composed by isolates that escape the PCV-13 vaccine, with patterns of tissue/niche segregation, adaptation and specialization. These findings suggest that the population structure of ocular pneumococcus may be shaped by multiple factors including PCV-13 selective pressure, microbial-related and niche-specific host-associated features.},
	issn = {2057-5858},
	doi = {10.1099/mgen.0.000763},
	author = {Andre, Camille and Rouhana, John and de Mello, Suelen Scarpa and da Cunha, Gabriela Rosa and Van Camp, Andrew G and Gilmore, Michael S and Bispo, Paulo J M}
}
@article {1661841,
	title = {Comparative In Vitro Activity of New Lipoglycopeptides and Vancomycin Against Ocular Staphylococci and Their Toxicity on the Human Corneal Epithelium},
	journal = {Cornea},
	volume = {42},
	number = {5},
	year = {2023},
	month = {2023 May 01},
	pages = {615-623},
	abstract = {PURPOSE: The purpose of this study was to assess the potential of new lipoglycopeptides as novel topical therapies for improved treatment of recalcitrant ocular infections. We evaluated the in vitro antimicrobial activity of oritavancin, dalbavancin, and telavancin compared with vancomycin (VAN) against a large collection of ocular staphylococcal isolates and their cytotoxicity on human corneal epithelial cells (HCECs). METHODS: Antimicrobial susceptibility testing was performed by broth microdilution against 223 Staphylococcus spp. clinical isolates. Time-kill kinetics were determined for methicillin-resistant strains of Staphylococcus aureus (MRSA) (n = 2) and Staphylococcus epidermidis (MRSE) (n = 1). In vitro cytotoxicity assays were performed with AlamarBlue and live/dead staining on HCECs. RESULTS: All new lipoglycopeptides showed strong in vitro potency against ocular staphylococci, including multidrug-resistant MRSA strains, with dalbavancin showing a slightly higher potency overall [minimum inhibitory concentration (MIC) 90 0.06 μg/mL] compared with telavancin and oritavancin (MIC 90 0.12 μg/mL), whereas VAN had the lowest potency (MIC 90 2 μg/mL). Oritavancin exerted rapid bactericidal activity within 1 h for MRSA and 2 h for MRSE. All other drugs were bactericidal within 24 h. At a concentration commonly used for topical preparations (25 mg/mL), cytotoxicity was observed for VAN after 5 min of incubation, whereas reduction in HCEC viability was not seen for telavancin and was less affected by oritavancin and dalbavancin. Cytotoxicity at 25 mg/mL was seen for all drugs at 30 and 60 min but was significantly reduced or undetected for lower concentrations. CONCLUSIONS: Our study demonstrates that new lipoglycopeptides have substantially better in vitro antimicrobial activity against ocular staphylococcal isolates compared with VAN, with a similar or improved toxicity profile on HCECs.},
	keywords = {Anti-Bacterial Agents, Epithelium, Corneal, Humans, Lipoglycopeptides, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Staphylococcal Infections, Staphylococcus, Vancomycin},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003197},
	author = {Andr{\'e}, Camille and Islam, Mohammad Mirazul and Paschalis, Eleftherios and Bispo, Paulo J M}
}
@article {1709791,
	title = {Microbiology of Eye Infections at the Massachusetts Eye and Ear: An 8-Year Retrospective Review Combined With Genomic Epidemiology},
	journal = {Am J Ophthalmol},
	volume = {255},
	year = {2023},
	month = {2023 Nov},
	pages = {43-56},
	abstract = {PURPOSE: Ocular bacterial infections are important causes of morbidity and vision loss. Early antimicrobial therapy is necessary to save vision, but their efficacy is increasingly compromised by antimicrobial resistance (AMR). We assessed the etiology of ocular bacterial infections seen at Massachusetts Eye and Ear and investigated the molecular epidemiology and AMR profiles of contemporary isolates. DESIGN: Laboratory investigation. METHODS: We used a combination of phenotypic tests and genome sequencing to identify the predominant lineages of leading ocular pathogens and their AMR profiles. RESULTS: A total of 1601 isolates were collected from 2014 to 2021, with Staphylococcus aureus (n\&nbsp;=\&nbsp;621), coagulase-negative staphylococci (CoNS) (n\&nbsp;=\&nbsp;234), Pseudomonas aeruginosa (n\&nbsp;=\&nbsp;213), Enterobacteriaceae (n\&nbsp;=\&nbsp;167), and Streptococcus pneumoniae (n\&nbsp;=\&nbsp;95) being the most common. Resistance was high among staphylococci, with methicillin resistance (MR) detected in 28\% of S aureus and 39.8\% of CoNS isolates. Multidrug resistance (MDR) was frequent among MR staphylococci (MRSA 60\%, MRCoNS 76.1\%). The population of S aureus isolates consisted mainly of 2 clonal complexes (CCs): CC8 (26.1\%) and CC5 (24.1\%). CC5 strains carried a variety of AMR markers, resulting in high levels of resistance to first-line therapies. Similarly, the population of ocular Staphylococcus epidermidis was homogenous with most belonging to CC2 (85\%), which were commonly MDR (48\%). Conversely, ocular S pneumoniae, P aeruginosa, and Enterobacteriaceae were often susceptible to first-line therapies and grouped into highly diverse genetic populations. CONCLUSION: Our data showed that ocular bacterial infections in our patient population are disproportionately caused by strains that are resistant to clinically relevant antibiotics and are associated with major epidemic genotypes with both community and hospital associations.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.06.016},
	author = {Andr{\'e}, Camille and Lebreton, Fran{\c c}ois and Van Tyne, Daria and Cadorette, James and Boody, Rick and Gilmore, Michael S and Bispo, Paulo J M}
}
@article {1351134,
	title = {B-scan ultrasonography following open globe repair},
	journal = {Eye (Lond)},
	volume = {28},
	number = {4},
	year = {2014},
	month = {2014 Apr},
	pages = {381-5},
	abstract = {PURPOSE: To examine the accuracy and predictive ability of B-scan ultrasonography in the post-repair assessment of an open globe injury. METHODS: In all, 965 open globe injuries treated at the Massachusetts Eye and Ear Infirmary between 1 January 2000 and 1 June 2010 were retrospectively reviewed. A total of 427 ultrasound reports on 210 patients were analyzed. Ultrasound reports were examined for the following characteristics: vitreous hemorrhage, vitreous tag, retinal tear, RD (including subcategories total RD, partial RD, closed funnel RD, open funnel RD, and chronic RD), vitreous traction, vitreous debris, serous choroidal detachment, hemorrhagic choroidal detachment, kissing choroidal detachment, dislocated crystalline lens, dislocated intraocular lens (IOL), disrupted crystalline lens, intraocular foreign body (IOFB), intraocular air, irregular posterior globe contour, disorganized posterior intraocular contents, posterior vitreous detachment, choroidal vs retinal detachment, vitreal membranes, and choroidal thickening. The main outcome measure was visual outcome at final follow-up. RESULTS: Among 427 B-scan reports, there were a total of 57 retinal detachments, 19 retinal tears, 18 vitreous traction, 59 serous choroidal detachments, 47 hemorrhagic choroidal detachments, and 10 kissing choroidal detachments. Of patients with multiple studies, 26\% developed retinal detachments or retinal tears on subsequent scans. Ultrasound had 100\% positive predictive value for diagnosing retinal detachment and IOFB. The diagnoses of retinal detachment, disorganized posterior contents, hemorrhagic choroidal detachment, kissing choroidal detachment, and irregular posterior contour were associated with worse visual acuity at final follow-up. Disorganized posterior contents correlated with particularly poor outcomes. CONCLUSIONS: B-scan ultrasonography is a proven, cost-effective imaging modality in the management of an open globe injury. This tool can offer both diagnostic and prognostic information, useful for both surgical planning and further medical management.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Eye Diseases, Eye Injuries, Penetrating, Female, Humans, Infant, Male, Middle Aged, Predictive Value of Tests, Regression Analysis, Reproducibility of Results, Retrospective Studies, Ultrasonography, Young Adult},
	issn = {1476-5454},
	doi = {10.1038/eye.2013.289},
	author = {Andreoli, M T and Yiu, G and Hart, L and Andreoli, C M}
}
@article {1364582,
	title = {Surgical rehabilitation of the open globe injury patient},
	journal = {Am J Ophthalmol},
	volume = {153},
	number = {5},
	year = {2012},
	month = {2012 May},
	pages = {856-60},
	abstract = {PURPOSE: To describe the long-term surgical course of patients with open globe injury. DESIGN: Retrospective case series. METHODS: Patients with open globe injuries (848 in total) treated surgically at the Massachusetts Eye and Ear Infirmary between 2000 and 2009 were retrospectively reviewed. Data from presentation, initial repair, and follow-up surgery were analyzed. RESULTS: Among 848 injuries, 1415 surgical procedures were performed. The mean follow-up time was 19.7 months, including 6017 visits. On average, patients required 1.7 surgeries and 7.1 follow-up visits. Factors predicting follow-up surgery included more severe ocular trauma score, worse prerepair visual acuity, retinal hemorrhage, anterior vitrectomy at primary repair, pars plana vitrectomy at primary repair, and lensectomy at primary repair. Patients with zone II injury, hemorrhagic choroidal detachment, and a history of previous ocular surgery tended to require follow-up surgery less frequently. Patients requiring a second surgery tended to have worse visual acuity at presentation and postrepair. Postoperative visual outcomes were worse for patients who underwent vitreoretinal follow-up surgery, likely because of mechanism of injury. Variables associated with inferior visual outcome were worse prerepair visual acuity, postoperative afferent pupillary defect (APD), old age, scleral laceration, and retinal detachment. CONCLUSION: Open globe injuries require significant surgical follow-up. Patients requiring multiple operations tended to have worse postoperative visual acuity. Patients who underwent vitreoretinal surgery had overall worse visual outcomes. While the first year of surveillance appears to be pivotal in the course of an open globe injury, these patients can expect long-term care from comprehensive and subspecialty ophthalmologists.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Corneal Injuries, Eye Enucleation, Eye Injuries, Penetrating, Female, Follow-Up Studies, Humans, Infant, Male, Middle Aged, Ophthalmologic Surgical Procedures, Retrospective Studies, Sclera, Time Factors, Vision Disorders, Visual Acuity, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2011.10.013},
	author = {Andreoli, Michael T and Andreoli, Christopher M}
}
@article {1635649,
	title = {Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate},
	journal = {Nat Commun},
	volume = {13},
	number = {1},
	year = {2022},
	month = {2022 Mar 15},
	pages = {1359},
	abstract = {Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90\% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.},
	issn = {2041-1723},
	doi = {10.1038/s41467-022-28969-3},
	author = {Andres-Mateos, Eva and Landegger, Lukas D and Unzu, Carmen and Phillips, Jean and Lin, Brian M and Dewyer, Nicholas A and Sanmiguel, Julio and Nicolaou, Fotini and Valero, Michelle D and Bourdeu, Kathrin I and Sewell, William F and Beiler, Rudolph J and McKenna, Michael J and Stankovic, Konstantina M and Vandenberghe, Luk H}
}
@article {1698356,
	title = {Non-Healing Corneal Ulcer and Uveitis Following Monkeypox Disease: Diagnostic and Therapeutic Challenges},
	journal = {Ocul Immunol Inflamm},
	year = {2023},
	month = {2023 May 04},
	pages = {1-6},
	abstract = {PURPOSE: The ocular manifestations of Monkeypox virus (Mpox) infection remain incompletely characterized. Our goal is to present a case series of non-healing corneal ulcers with associated uveitis caused by Mpox infection as well as management recommendations for Mpox-related ophthalmic disease (MPXROD). METHODS: Retrospective case series. RESULTS: Two male patients with recent hospitalization for systemic Mpox infection presented with non-healing corneal ulcer associated with anterior uveitis and severe IOP elevation. Despite initiation of conservative medical treatment including corticosteroid treatment for uveitis, in both cases, there was clinical progression with enlarging cornea lesions. Both cases received oral tecovirimat with complete healing of the corneal lesion. CONCLUSIONS: Corneal ulcer and anterior uveitis are rare complications of Mpox infection. Although Mpox disease is generally anticipated to be self-limited, tecovirimat may be an effective intervention in poorly healing Mpox keratitis. Corticosteroids should be used with caution in Mpox uveitis, as they might lead to worsening infection.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2023.2202746},
	author = {Androudi, Sofia and Kaufman, Aaron R and Kouvalakis, Alexandros and Mitsios, Andreas and Sapounas, Spyros and Al-Khatib, Danial and Schibler, Manuel and Pineda, Roberto and Baglivo, Edoardo}
}
@article {397766,
	title = {MEF2D Drives Photoreceptor Development through a Genome-wide Competition for Tissue-Specific Enhancers.},
	journal = {Neuron},
	volume = {86},
	number = {1},
	year = {2015},
	month = {2015 Apr 8},
	pages = {247-63},
	abstract = {Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. MEF2 transcription factors (TFs) play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina MEF2D binds to retina-specific enhancers and controls photoreceptor cell development. MEF2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits MEF2D away from canonical MEF2 binding sites and redirects it to retina-specific enhancers that lack the consensus MEF2-binding sequence. Once bound to retina-specific enhancers, MEF2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs and through selective activation of these enhancers to regulate tissue-specific genes.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2015.02.038},
	author = {Andzelm, Milena M and Cherry, Timothy J and Harmin, David A and Boeke, Annabel C and Lee, Charlotte and Hemberg, Martin and Pawlyk, Basil and Malik, Athar N and Flavell, Steven W and Sandberg, Michael A and Raviola, Elio and Greenberg, Michael E}
}
@article {1635656,
	title = {Effects of Subcutaneous Repository Corticotropin Gel Injection on Regulatory T Cell Population in Noninfectious Retinal Vasculitis},
	journal = {Ocul Immunol Inflamm},
	volume = {31},
	number = {3},
	year = {2023},
	month = {2023 Apr},
	pages = {556-565},
	abstract = {AIM: To evaluate the effect of repository corticotropin injection (RCI) on regulatory T cell population in patients with noninfectious retinal vasculitis. PATIENTS AND METHODS: Patients with active noninfectious retinal vasculitis were included in a prospective nonrandomized open-label study. RESULTS: Eighteen patients (33 eyes) were included in the study. Eleven (61.1\%) patients [20 (60.6\%) eyes] and 7 (38.9\%) patients [13 (33.3\%) eyes] were in the responsive and non-responsive groups, respectively. We did not find any statistically significant difference within the PPP-R group, within the PPP-NR group, or between these two groups in regard to regulatory T cell population. No significant systemic or ocular complications were found. CONCLUSION: RCI may be a complementary treatment in patients with non-infectious retinal vasculitis with or without uveitis. This study did not demonstrate an increase in regulatory T cell population in patients with noninfectious retinal vasculitis.},
	keywords = {Adrenocorticotropic Hormone, Humans, Prospective Studies, Retinal Vasculitis, T-Lymphocytes, Regulatory, Uveitis},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2042323},
	author = {Anesi, Stephen D and Chang, Peter Y and Maleki, Arash and Manhapra, Ambika and Look-Why, Sydney and Asgari, Soheila and Walsh, Marisa and Drenen, Kayla and Foster, C Stephen}
}
@article {1498257,
	title = {Reliability of Conjunctival Biopsy for Diagnosis of Ocular Mucous Membrane Pemphigoid: Redetermination of the Standard for Diagnosis and Outcomes of Previously Biopsy-Negative Patients},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Mar 04},
	pages = {1-8},
	abstract = {: To demonstrate the reliability of conjunctival biopsy analyzed by direct immunofluorescence (DIF) and supplemented with avidin-biotin complex immunoperoxidase (ABC) in diagnosing oMMP, and report therapy response in biopsy-positive patients, particularly when previously biopsy-negative elsewhere.: Retrospective outcomes review of 136 consecutive patients after conjunctival biopsy for suspected oMMP.: Among 136 patients, 66\% were diagnosed with oMMP by DIF and 13\% via supplemental ABC immunoperoxidase. Sensitivity increased from 79.6\% with DIF to 95.6\% with supplemental ABC. Among 57 biopsy-positive patients, 77\% were in remission at 1-year follow-up and 88\% after 2 years. Of 34 previous biopsy-negative but now biopsy-positive patients with a 2-year follow-up, 91\% achieved remission, including all 16 diagnosed via DIF and ABC.: Conjunctival biopsy analyzed by histopathology and DIF supplemented by ABC has high reliability for diagnosing oMMP and is a useful tool to use before starting long-term immunomodulatory therapy in a patient with suspected oMMP.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1716988},
	author = {Anesi, Stephen D and Eggenschwiler, Laura and Ferrara, Mariantonia and Artornsombudh, Pichaporn and Walsh, Marisa and Foster, C Stephen}
}
@article {836761,
	title = {A fully automated tortuosity quantification system with application to corneal nerve fibres in confocal microscopy images.},
	journal = {Med Image Anal},
	volume = {32},
	year = {2016},
	month = {2016 Aug},
	pages = {216-32},
	abstract = {Recent clinical research has highlighted important links between a number of diseases and the tortuosity of curvilinear anatomical structures like corneal nerve fibres, suggesting that tortuosity changes might detect early stages of specific conditions. Currently, clinical studies are mainly based on subjective, visual assessment, with limited repeatability and inter-observer agreement. To address these problems, we propose a fully automated framework for image-level tortuosity estimation, consisting of a hybrid segmentation method and a highly adaptable, definition-free tortuosity estimation algorithm. The former combines an appearance model, based on a Scale and Curvature-Invariant Ridge Detector (SCIRD), with a context model, including multi-range learned context filters. The latter is based on a novel tortuosity estimation paradigm in which discriminative, multi-scale features can be automatically learned for specific anatomical objects and diseases. Experimental results on 140 in vivo confocal microscopy images of corneal nerve fibres from healthy and unhealthy subjects demonstrate the excellent performance of our method compared to state-of-the-art approaches and ground truth annotations from 3 expert observers.},
	issn = {1361-8423},
	doi = {10.1016/j.media.2016.04.006},
	author = {Annunziata, Roberto and Kheirkhah, Ahmad and Aggarwal, Shruti and Hamrah, Pedram and Trucco, Emanuele}
}
@article {669276,
	title = {Two-Dimensional Plane for Multi-Scale Quantification of Corneal Subbasal Nerve Tortuosity.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {3},
	year = {2016},
	month = {2016 Mar 1},
	pages = {1132-9},
	abstract = {PURPOSE: To assess the performance of a novel system for automated tortuosity estimation and interpretation. METHODS: A supervised strategy (driven by observers{\textquoteright} grading) was employed to automatically identify the combination of tortuosity measures (i.e., tortuosity representation) leading to the best agreement with the observers. We investigated 18 tortuosity measures including curvature and density of inflection points, computed at multiple spatial scales. To leverage tortuosity interpretation, we propose the tortuosity plane (TP) onto which each image is mapped. Experiments were carried out on 140 images of subbasal nerve plexus of the central cornea, covering four levels of tortuosity. Three experienced observers graded each image independently. RESULTS: The best tortuosity representation was the combination of mean curvature at spatial scales 2 and 5. These tortuosity measures were the axes of the proposed TP (interpretation). The system for tortuosity estimation revealed strong agreement with the observers on a global and per-level basis. The agreement with each observer (Spearman{\textquoteright}s correlation) was statistically significant (αs = 0.05, P \&lt; 0.0001) and higher than that of at least one of the other observers in two out of three cases (ρOUR = 0.7594 versus ρObs3 = 0.7225; ρOUR = 0.8880 versus ρObs1 = 0.8017, ρObs3 = 0.7315). Based on paired-sample t-tests, these improvements were significant (P \&lt; 0.001). CONCLUSIONS: Our automated system stratifies images by four tortuosity levels (discrete scale) matching or exceeding the accuracy of experienced observers. Of importance, the TP allows the assessment of tortuosity on a two-dimensional continuous scale, thus leading to a finer discrimination among images.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18513},
	author = {Annunziata, Roberto and Kheirkhah, Ahmad and Aggarwal, Shruti and Cavalcanti, Bernardo M and Hamrah, Pedram and Trucco, Emanuele}
}
@article {1470981,
	title = {Analysis of Neuroretinal Rim by Age, Race, and Sex Using High-Density 3-Dimensional Spectral-Domain Optical Coherence Tomography},
	journal = {J Glaucoma},
	volume = {28},
	number = {11},
	year = {2019},
	month = {2019 Nov},
	pages = {979-988},
	abstract = {PR{\'e}CIS:: Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes. PURPOSE: To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes. METHODS: A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch{\textquoteright}s membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements. RESULTS: The population was 57\% female and 69\% white with a mean age of 58.4{\textpm}15.3 years. The mean MDB thickness in the normal population was 278.4{\textpm}47.5 {\textmu}m. For this normal population, MDB thickness decreased by 0.84 {\textmu}m annually (P\&lt;0.001). African Americans had thinner MDBs compared with whites (P=0.003). Males and females had similar MDB thickness values (P=0.349). CONCLUSION: Neuroretinal rim MDB thickness measurements decreased significantly with age. African Americans had thinner MDB neuroretinal rims than whites.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001381},
	author = {Antar, Hussein and Tsikata, Edem and Ratanawongphaibul, Kitiya and Zhang, Jing and Shieh, Eric and Lee, Ramon and Freeman, Madeline and Papadogeorgou, Georgia and Simavli, Huseyin and Que, Christian and Verticchio Vercellin, Alice C and Khoueir, Ziad and de Boer, Johannes F and Chen, Teresa C}
}
@article {1573111,
	title = {Current understanding of the molecular and cellular pathology of diabetic retinopathy},
	journal = {Nat Rev Endocrinol},
	volume = {17},
	number = {4},
	year = {2021},
	month = {2021 04},
	pages = {195-206},
	abstract = {Diabetes mellitus has profound effects on multiple organ systems; however, the loss of vision caused by diabetic retinopathy might be one of the most impactful in a patient{\textquoteright}s life. The retina is a highly metabolically active tissue that requires a complex interaction of cells, spanning light sensing photoreceptors to neurons that transfer the electrochemical signal to the brain with support by glia and vascular tissue. Neuronal function depends on a complex inter-dependency of retinal cells that includes the formation of a blood-retinal barrier. This dynamic system is negatively affected by diabetes mellitus, which alters normal cell-cell interactions and leads to profound vascular abnormalities, loss of the blood-retinal barrier and impaired neuronal function. Understanding the normal cell signalling interactions and how they are altered by diabetes mellitus has already led to novel therapies that have improved visual outcomes in many patients. Research highlighted in this Review has led to a new understanding of retinal pathophysiology during diabetes mellitus and has uncovered potential new therapeutic avenues to treat this debilitating disease.},
	keywords = {Animals, Blood-Retinal Barrier, Diabetic Retinopathy, Humans, Neurons, Neurovascular Coupling, Signal Transduction},
	issn = {1759-5037},
	doi = {10.1038/s41574-020-00451-4},
	author = {Antonetti, David A and Silva, Paolo S and Stitt, Alan W}
}
@article {1559557,
	title = {Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial},
	journal = {JAMA},
	volume = {324},
	number = {23},
	year = {2020},
	month = {2020 Dec 15},
	pages = {2383-2395},
	abstract = {Importance: Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown. Objective: To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy. Design, Setting, and Participants: Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020. Interventions: Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria. Main Outcomes and Measures: The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years. Results: Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56\%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95\% (195 of 205) completed the 24-week visit and 90\% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95\% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95\% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95\% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95\% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95\% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33\%) assigned to aflibercept received vitrectomy and 34 eyes (32\%) assigned to vitrectomy received subsequent aflibercept. Conclusions and Relevance: Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95\% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation. Trial Registration: ClinicalTrials.gov Identifier: NCT02858076.},
	issn = {1538-3598},
	doi = {10.1001/jama.2020.23027},
	author = {Antoszyk, Andrew N and Glassman, Adam R and Beaulieu, Wesley T and Jampol, Lee M and Jhaveri, Chirag D and Punjabi, Omar S and Salehi-Had, Hani and Wells, John A and Maguire, Maureen G and Stockdale, Cynthia R and Martin, Daniel F and Sun, Jennifer K and DRCR Retina Network}
}
@article {1688361,
	title = {Successful treatment of idiopathic retinal vasculitis with rituximab in two patients},
	journal = {Am J Ophthalmol Case Rep},
	volume = {30},
	year = {2023},
	month = {2023 Jun},
	pages = {101844},
	abstract = {PURPOSE: To describe results of treatment of idiopathic retinal vasculitis with intravenous rituximab. OBSERVATIONS: We present two patients with idiopathic retinal vasculitis who required steroid-sparing therapy and achieved steroid-free remission with intravenous rituximab. Rituximab was used as a first-line steroid-sparing agent after steroids in one patient and as a second-line steroid-sparing agent in the other patient. Both patients achieved steroid-free remission of disease with follow up of at least one year after rituximab initiation. CONCLUSIONS AND IMPORTANCE: Rituximab achieved steroid-free remission in two patients with idiopathic retinal vasculitis. It should be considered as a treatment option in these patients.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2023.101844},
	author = {Apivatthakakul, Atitaya and Liu, Renee and Sobrin, Lucia}
}
@article {987926,
	title = {Elevated Neutrophil Elastase in Tears of Ocular Graft-Versus-Host Disease Patients},
	journal = {Am J Ophthalmol},
	volume = {176},
	year = {2017},
	month = {2017 Apr},
	pages = {46-52},
	abstract = {PURPOSE: To investigate the levels of neutrophil elastase (NE), matrix metalloproteinases (MMPs), and myeloperoxidase (MPO) in tear washes of patients with ocular graft-vs-host disease (oGVHD). DESIGN: Case-control study. METHODS: Based on established criteria, oGVHD patients (n\&nbsp;= 14; 28 eyes) and age-/sex-matched healthy controls (n\&nbsp;= 14; 28 eyes) were enrolled. Tear washes were collected and analyzed for NE using a single-analyte enzyme-linked immunosorbent assay (ELISA). MMPs (1, 2, 3, 7, 8, 9, 12), MPO, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were analyzed using multianalyte bead-based ELISA assays. Total MMP activity was measured using a fluorimetric assay. Correlation studies were performed between NE, MMP-8, MMP-9, and MPO within study groups. RESULTS: NE, MMP-8, MMP-9, and MPO levels were elevated in oGVHD tears when compared with controls (P \&lt; .0001). NE was the most elevated analyte. MMP activity was higher and TIMP-1 levels were lower in oGVHD than in control (P \&lt; .0001). In oGVHD, NE significantly correlated with MMP-8 (r\&nbsp;= 0.92), MMP-9 (r\&nbsp;= 0.90), and MPO (r\&nbsp;= 0.79) (P \&lt; .0001). MMP-8 correlated with MMP-9 (r\&nbsp;= 0.96, P \&lt; .0001), and MPO (r\&nbsp;= 0.60, P\&nbsp;= .001). MMP-9 correlated with MPO (r\&nbsp;= 0.55, P\&nbsp;= .002). In controls, NE, MMP-9, and MPO significantly correlated with each other (P \&lt; .0001). CONCLUSIONS: The marked increase in NE in oGVHD tears that correlated strongly with elevated MMP-8, MMP-9, and MPO suggests a common neutrophilic source and provides evidence of neutrophil activity on the ocular surface of oGVHD patients.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.12.026},
	author = {Arafat, Samer N and Robert, Marie-Claude and Abud, Tulio and Spurr-Michaud, Sandra and Amparo, Francisco and Dohlman, Claes H and Dana, Reza and Gipson, Ilene K}
}
@article {281106,
	title = {UV cross-linking of donor corneas confers resistance to keratolysis.},
	journal = {Cornea},
	volume = {33},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {955-9},
	abstract = {PURPOSE: The aim of this study was to develop a modified ex vivo corneal cross-linking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. METHODS: Ex vivo cross-linking of human corneas was performed using Barron artificial anterior chambers. The corneas were deepithelialized, pretreated with riboflavin solution (0.1\% riboflavin/20\% dextran), and irradiated with ultraviolet A (UV-A) light (λ = 370 nm, irradiance = 3 mW/cm) for various durations. The combined effect of UV-A and gamma (γ) irradiation was also assessed using the commercially available γ-irradiated corneal donors. The corneas were then trephined and incubated at 37{\textdegree}C with 0.3\% collagenase A solution. The time to dissolution of each cornea was compared across treatments. RESULTS: Deepithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 {\textpm} 0.6 hours. Cross-linked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 {\textpm} 2.6 hours (P \&lt; 0.0001). The corneal tissues{\textquoteright} resistance to collagenase increased with longer UV-A exposure, reaching a plateau at 30 minutes. Cross-linking both the anterior and posterior corneas did not provide added resistance when compared with cross-linking the anterior corneas only (P \&gt; 0.05). γ-irradiated corneas dissolved as readily as deepithelialized controls regardless of whether they were further cross-linked (5.6 {\textpm} 1.2 hours) or not (6.1 {\textpm} 0.6 hours) (P = 0.43). CONCLUSIONS: Collagen cross-linking of the deepithelialized anterior corneal surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000185},
	author = {Arafat, Samer N and Robert, Marie-Claude and Shukla, Anita N and Dohlman, Claes H and Chodosh, James and Ciolino, Joseph B}
}
@article {1626102,
	title = {shsA: A novel orthologous of sasX/sesI virulence genes is detected in Staphylococcus haemolyticus Brazilian strains},
	journal = {Infect Genet Evol},
	volume = {97},
	year = {2022},
	month = {2022 Jan},
	pages = {105189},
	abstract = {The surface protein SasX, has a key role in methicillin-resistant Staphylococcus aureus (MRSA) colonization and pathogenesis, and has been associated with the epidemic success of some MRSA clones. To date, only one SasX homologous protein, named SesI, has been described in Staphylococcus epidermidis. In this work, we analyze the occurrence of the sasX gene and its genetic environment in Staphylococcus haemolyticus S. haemolyticus clinical strains (n\&nbsp;=\&nbsp;62) were screened for the presence of the sasX gene and its carrier, the prophage Φ SPβ-like. A deep characterization was done in one strain (MD43), through which we determined the complete nucleotide sequence for the S. haemolitycus sasX-like gene. Whole genome sequencing of strain MD43 was performed, and the gene, termed here because of its unique attributes, shsA, was mapped to the Φ SPβ-like prophage sequence. The shsA gene was detected in 33 out of 62 strains showing an average identity of 92 and 96\% with the sasX and sesI genes and at the amino acid level, 88\% identity with SasX and 92\% identity with SesI. The ~124Kb Φ SPβ-like prophage sequence showed a largely intact prophage compared to its counterpart in S. epidermidis strain RP62A, including the sesI insertion site. In conclusion, we identified a new sasX ortholog in S. haemolyticus (shsA). Its horizontal spread from this reservoir could represent an emergent threat in healthcare facilities since so far, no S. aureus sasX+ strains have been reported in Brazil.},
	issn = {1567-7257},
	doi = {10.1016/j.meegid.2021.105189},
	author = {Araujo-Alves, Amanda V and Kraychete, Gabriela B and Gilmore, Michael S and Barros, Elaine M and Giambiagi-deMarval, Marcia}
}
@article {382556,
	title = {From pathobiology to the targeting of pericytes for the treatment of diabetic retinopathy.},
	journal = {Curr Diab Rep},
	volume = {15},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {573},
	abstract = {Pericytes, the mural cells that constitute the capillaries along with endothelial cells, have been associated with the pathobiology of diabetic retinopathy; however, therapeutic implications of this association remain largely unexplored. Pericytes appear to be highly susceptible to the metabolic challenges associated with a diabetic environment, and there is substantial evidence that their loss may contribute to microvascular instability leading to the formation of microaneurysms, microhemorrhages, acellular capillaries, and capillary nonperfusion. Since pericytes are strategically located at the interface between the vascular and neural components of the retina, they offer extraordinary opportunities for therapeutic interventions in diabetic retinopathy. Moreover, the availability of novel imaging methodologies now allows for the in vivo visualization of pericytes, enabling a new generation of clinical trials that use pericyte tracking as clinical endpoints. The recognition of multiple signaling mechanisms involved in pericyte development and survival should allow for a renewed interest in pericytes as a therapeutic target for diabetic retinopathy.},
	issn = {1539-0829},
	doi = {10.1007/s11892-014-0573-2},
	author = {Arboleda-Velasquez, Joseph F and Valdez, Cammi N and Marko, Christina K and D{\textquoteright}Amore, Patricia A}
}
@article {1474214,
	title = {Resistance to autosomal dominant Alzheimer{\textquoteright}s disease in an APOE3 Christchurch homozygote: a case report},
	journal = {Nat Med},
	volume = {25},
	number = {11},
	year = {2019},
	month = {2019 Nov},
	pages = {1680-1683},
	abstract = {We identified a PSEN1 (presenilin 1) mutation carrier from the world{\textquoteright}s largest autosomal dominant Alzheimer{\textquoteright}s disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer{\textquoteright}s disease.},
	issn = {1546-170X},
	doi = {10.1038/s41591-019-0611-3},
	author = {Arboleda-Velasquez, Joseph F and Lopera, Francisco and O{\textquoteright}Hare, Michael and Delgado-Tirado, Santiago and Marino, Claudia and Chmielewska, Natalia and Saez-Torres, Kahira L and Amarnani, Dhanesh and Schultz, Aaron P and Sperling, Reisa A and Leyton-Cifuentes, David and Chen, Kewei and Baena, Ana and Aguillon, David and Rios-Romenets, Silvia and Giraldo, Margarita and Guzm{\'a}n-V{\'e}lez, Edmarie and Norton, Daniel J and Pardilla-Delgado, Enmanuelle and Artola, Arabiye and Sanchez, Justin S and Acosta-Uribe, Juliana and Lalli, Matthew and Kosik, Kenneth S and Huentelman, Matthew J and Zetterberg, Henrik and Blennow, Kaj and Reiman, Rebecca A and Luo, Ji and Chen, Yinghua and Thiyyagura, Pradeep and Su, Yi and Jun, Gyungah R and Naymik, Marcus and Gai, Xiaowu and Bootwalla, Moiz and Ji, Jianling and Shen, Lishuang and Miller, John B and Kim, Leo A and Tariot, Pierre N and Johnson, Keith A and Reiman, Eric M and Quiroz, Yakeel T}
}
@article {1615226,
	title = {Safe and Effective Disease-Modifying Therapies for Small Blood Vessel Disease in the Brain},
	journal = {Am J Pathol},
	volume = {191},
	number = {11},
	year = {2021},
	month = {2021 11},
	pages = {1852-1855},
	keywords = {Alzheimer Disease, Animals, Cerebral Small Vessel Diseases, Humans},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.09.003},
	author = {Arboleda-Velasquez, Joseph F}
}
@article {283991,
	title = {Notch signaling functions in retinal pericyte survival},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {8},
	year = {2014},
	month = {2014 Jul 11},
	pages = {5191-9},
	abstract = {PURPOSE: Pericytes, the vascular cells that constitute the outer layer of capillaries, have been shown to have a crucial role in vascular development and stability. Loss of pericytes precedes endothelial cell dysfunction and vascular degeneration in small-vessel diseases, including diabetic retinopathy. Despite their clinical relevance, the cellular pathways controlling survival of retinal pericytes remain largely uncharacterized. Therefore, we investigated the role of Notch signaling, a master regulator of cell fate decisions, in retinal pericyte survival. METHODS: A coculture system of ligand-dependent Notch signaling was developed using primary cultured retinal pericytes and a mesenchymal cell line derived from an inducible mouse model expressing the Delta-like 1 Notch ligand. This model was used to examine the effect of Notch activity on pericyte survival using quantitative PCR (qPCR) and a light-induced cell death assay. The effect of Notch gain- and loss-of-function was analyzed in monocultures of retinal pericytes using antibody arrays to interrogate the expression of apoptosis-related proteins. RESULTS: Primary cultured retinal pericytes differentially expressed key molecules of the Notch pathway and displayed strong expression of canonical Notch/RBPJK (recombination signal-binding protein 1 for J-kappa) downstream targets. A gene expression screen using gain- and loss-of-function approaches identified genes relevant to cell survival as downstream targets of Notch activity in retinal pericytes. Ligand-mediated Notch activity protected retinal pericytes from light-induced cell death. CONCLUSIONS: Our results have identified signature genes downstream of Notch activity in retinal pericytes and suggest that tight regulation of Notch signaling is crucial for pericyte survival.},
	keywords = {Animals, Cattle, Cell Survival, Coculture Techniques, Mesenchymal Stromal Cells, Models, Animal, Pericytes, Polymerase Chain Reaction, Proto-Oncogene Proteins, Receptors, Notch, Retina, Signal Transduction},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14046},
	author = {Arboleda-Velasquez, Joseph F and Primo, Vincent and Graham, Mark and James, Alexandra and Manent, Jan and D{\textquoteright}Amore, Patricia A}
}
@article {959371,
	title = {The origin and evolution of cell types.},
	journal = {Nat Rev Genet},
	volume = {17},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {744-757},
	abstract = {Cell types are the basic building blocks of multicellular organisms and are extensively diversified in animals. Despite recent advances in characterizing cell types, classification schemes remain ambiguous. We propose an evolutionary definition of a cell type that allows cell types to be delineated and compared within and between species. Key to cell type identity are evolutionary changes in the {\textquoteright}core regulatory complex{\textquoteright} (CoRC) of transcription factors, that make emergent sister cell types distinct, enable their independent evolution and regulate cell type-specific traits termed apomeres. We discuss the distinction between developmental and evolutionary lineages, and present a roadmap for future research.},
	issn = {1471-0064},
	doi = {10.1038/nrg.2016.127},
	author = {Arendt, Detlev and Musser, Jacob M and Baker, Clare V H and Bergman, Aviv and Cepko, Connie and Erwin, Douglas H and Pavlicev, Mihaela and Schlosser, Gerhard and Widder, Stefanie and Laubichler, Manfred D and Wagner, G{\"u}nter P}
}
@article {1532359,
	title = {Galectins as Regulators of Corneal Inflammation},
	journal = {Curr Opin Physiol},
	volume = {19},
	year = {2021},
	month = {2021 Feb},
	pages = {17-21},
	abstract = {The cornea is a transparent avascular tissue on the anterior segment of the eye responsible for providing refractive power and forming a protective barrier against the external environment. Infectious and inflammatory conditions can compromise the structure of the cornea, leading to visual impairment and blindness. Galectins are a group of β-galactoside-binding proteins expressed by immune and non-immune cells that play pivotal roles in innate and adaptive immunity. In this brief review, we discuss how different members of this family of proteins affect both pro-inflammatory and anti-inflammatory responses in the cornea, particularly in the context of infection, transplantation and wound healing. We further describe recent research showing beneficial effects of galectin-targeted therapy in corneal diseases.},
	issn = {2468-8673},
	doi = {10.1016/j.cophys.2020.08.021},
	author = {Arg{\"u}eso, Pablo}
}
@article {1460351,
	title = {Disrupted Glycocalyx as a Source of Ocular Surface Biomarkers},
	journal = {Eye Contact Lens},
	volume = {46 Suppl 2},
	year = {2020},
	month = {2020 Mar},
	pages = {S53-S56},
	abstract = {The glycocalyx is a dense and diverse coat of glycans and glycoconjugates responsible for maintaining cell surface integrity and regulating the interaction of cells with the external environment. Transmembrane mucins such as MUC1 and MUC16 comprise a major component of the epithelial glycocalyx and are currently used to monitor disease progression in cancer. At the ocular surface, multiple lines of evidence indicate that abnormal expression of the enzymes responsible for glycan biosynthesis during pathological conditions impairs the glycosylation of transmembrane mucins. It is now becoming clear that these changes contribute to modify the interaction of mucins with galectin-3, a multimeric lectin crucial for preserving the ocular surface epithelial barrier. This review highlights the potential of using the epithelial glycocalyx as a reliable source for the generation of biomarkers to diagnose and monitor ocular surface disease.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000653},
	author = {Arg{\"u}eso, Pablo}
}
@article {1363242,
	title = {Glycobiology of the ocular surface: mucins and lectins},
	journal = {Jpn J Ophthalmol},
	volume = {57},
	number = {2},
	year = {2013},
	month = {2013 Mar},
	pages = {150-5},
	abstract = {Glycosylation is an important and common form of posttranscriptional modification of proteins in cells. During the last decade, a vast array of biological functions has been ascribed to glycans because of a rapid evolution in glycomic technologies. Glycogenes that are highly expressed at the human ocular surface include families of glycosyltransferases, proteoglycans, and glycan degradation proteins, as well as mucins and carbohydrate-binding proteins, such as the galectins. On the apical glycocalyx, mucin O-glycans promote boundary lubrication, prevent bacterial adhesion and endocytic activity, and maintain epithelial barrier function through interactions with galectins. The emerging roles attributed to glycans are contributing to the appreciation of their biological capabilities at the ocular surface.},
	keywords = {Animals, Bacterial Adhesion, Biological Transport, Cornea, Epithelium, Corneal, Galectins, Glycocalyx, Glycomics, Glycosylation, Glycosyltransferases, Humans, Lectins, Mucins, Polysaccharides, Protein Processing, Post-Translational},
	issn = {1613-2246},
	doi = {10.1007/s10384-012-0228-2},
	author = {Arg{\"u}eso, Pablo}
}
@article {1626097,
	title = {Human ocular mucins: The endowed guardians of sight},
	journal = {Adv Drug Deliv Rev},
	volume = {180},
	year = {2022},
	month = {2022 Jan},
	pages = {114074},
	abstract = {Mucins are an ancient group of glycoproteins that provide viscoelastic, lubricating and hydration properties to fluids bathing wet surfaced epithelia. They are involved in the protection of underlying tissues by forming a barrier with selective permeability properties. The expression, processing and spatial distribution of mucins are often determined by organ-specific requirements that in the eye involve protecting against environmental insult while allowing the passage of light. The human ocular surface epithelia have evolved to produce an extremely thin and watery tear film containing a distinct soluble mucin product secreted by goblet cells outside the visual axis. The adaptation to the ocular environment is notably evidenced by the significant contribution of transmembrane mucins to the tear film, where they can occupy up to one-quarter of its total thickness. This article reviews the tissue-specific properties of human ocular mucins, methods of isolation and detection, and current approaches to model mucin systems recapitulating the human ocular surface mucosa. This knowledge forms the fundamental basis to develop applications with a promising biological and clinical impact.},
	issn = {1872-8294},
	doi = {10.1016/j.addr.2021.114074},
	author = {Arg{\"u}eso, Pablo}
}
@article {1043191,
	title = {Proteolytic activity in the meibomian gland: Implications to health and disease},
	journal = {Exp Eye Res},
	volume = {163},
	year = {2017},
	month = {2017 Oct},
	pages = {53-57},
	abstract = {The function of the meibomian gland in the upper and lower eyelids is critical to maintaining homeostasis at the ocular surface. Highly specialized meibocytes within the gland must differentiate and accumulate intracellular lipid droplets that are released into the tear film following rupture of the cell membrane. Proteases and their inhibitors have been recognized as key players in remodeling extracellular matrices and promoting the normal integrity of glandular tissue. They modulate a wide range of biological processes, such as cell proliferation and differentiation, and can contribute to disease when aberrantly expressed. Deciphering the role of proteolytic activity in the meibomian gland offers an opportunity to gain a more comprehensive and fundamental understanding of the developmental, physiological, and pathological processes associated with this gland.},
	keywords = {Aging, Dry Eye Syndromes, Extracellular Matrix, Humans, Meibomian Glands, Metalloproteases, Peptide Hydrolases, Proteolysis, Sebaceous Glands},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2017.03.001},
	author = {Arg{\"u}eso, Pablo}
}
@article {1549022,
	title = {Retinal Imaging Findings in Carriers With PSEN1-Associated Early-Onset Familial Alzheimer Disease Before Onset of Cognitive Symptoms},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {1},
	year = {2021},
	month = {2021 Jan 01},
	pages = {49-56},
	abstract = {Importance: Individuals with autosomal dominant mutations for Alzheimer disease are valuable in determining biomarkers present prior to the onset of cognitive decline, improving the ability to diagnose Alzheimer disease as early as possible. Optical coherence tomography (OCT) has surfaced as a potential noninvasive technique capable of analyzing central nervous system tissues for biomarkers of Alzheimer disease. Objective: To evaluate whether OCT can detect early retinal alterations in carriers of the presenilin 1 (PSEN1 [OMIM 104311]) E280A mutation who are cognitively unimpaired. Design, Setting, and Participants: A cross-sectional imaging study conducted from July 13, 2015, to September 16, 2020, included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired and 10 healthy noncarrier family members, all leveraged from a homogenous Colombian kindred. Statistical analysis was conducted from September 9, 2017, to September 16, 2020. Main Outcomes and Measures: Mixed-effects multiple linear regression was performed to compare the thickness values of the whole retina and individual retinal layers on OCT scans between mutation carriers and noncarriers. Simple linear-effects and mixed-effects multiple linear regression models were used to assess whether age was an effect modifier for PSEN1 mutation of amyloid β levels and retinal thickness, respectively. Fundus photographs were used to compare the number of arterial and venous branch points, arterial and venous tortuosity, and fractal dimension. Results: This study included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired (7 women [70\%]; mean [SD] age, 36.3 [8.1] years) and 10 healthy noncarrier family members (7 women [70\%]; mean [SD] age, 36.4 [8.2] years). Compared with noncarrier controls, PSEN1 mutation carriers who were cognitively unimpaired had a generalized decrease in thickness of the whole retina as well as individual layers detected on OCT scans, with the inner nuclear layer (outer superior quadrant, β = -3.06; P = .007; outer inferior quadrant, β = -2.60; P = .02), outer plexiform layer (outer superior quadrant, β = -3.44; P = .03), and outer nuclear layer (central quadrant, β = -8.61; P = .03; inner nasal quadrant, β = -8.39; P = .04; inner temporal quadrant, β = -9.39; P = .02) showing the greatest amount of statistically significant thinning. Age was a significant effect modifier for the association between PSEN1 mutation and amyloid β levels in cortical regions (β = 0.03; P = .001) but not for the association between PSEN1 mutation and retinal thickness. No statistical difference was detected in any of the vascular parameters studied. Conclusions and Relevance: These findings suggest that OCT can detect functional and morphologic changes in the retina of carriers of familial Alzheimer disease who are cognitively unimpaired several years before clinical onset, suggesting that OCT findings and retinal vascular parameters may be biomarkers prior to the onset of cognitive decline.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.4909},
	author = {Armstrong, Grayson W and Kim, Leo A and Vingopoulos, Filippos and Park, Jeayoung and Garg, Itika and Kasetty, Megan and Silverman, Rebecca F and Zeng, Rebecca and Douglas, Vivian Paraskevi and Lopera, Francisco and Baena, Ana and Giraldo, Margarita and Norton, Dan and Cronin-Golomb, Alice and Arboleda-Velasquez, Joseph F and Quiroz, Yakeel T and Miller, John B}
}
@article {1632290,
	title = {Telemedicine for the Diagnosis and Management of Age-Related Macular Degeneration: A Review},
	journal = {J Clin Med},
	volume = {11},
	number = {3},
	year = {2022},
	month = {2022 Feb 05},
	abstract = {Use of ophthalmic telemedicine for patients with age-related macular degeneration (AMD) has shown remarkable advances over recent years. The recent COVID pandemic accelerated this transition since in-person evaluation of elderly patients at high risk for advanced AMD and severe vision loss were also at higher risk for complications from COVID infection. To date, ophthalmic telemedicine has been successfully used in remote retinal consultation by general ophthalmologists for AMD management, hybrid testing visits with both in-office testing and remote evaluation, as well as early successes in home-based remote monitoring of patients with high-risk AMD. We therefore review the current literature and evidence base related to ophthalmic telemedicine for AMD.},
	issn = {2077-0383},
	doi = {10.3390/jcm11030835},
	author = {Armstrong, Grayson W and Miller, John B}
}
@article {1586184,
	title = {Anterior Segment Imaging Devices in Ophthalmic Telemedicine},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {149-156},
	abstract = {Obtaining a clear assessment of the anterior segment is critical for disease diagnosis and management in ophthalmic telemedicine. The anterior segment can be imaged with slit lamp cameras, robotic remote controlled slit lamps, cell phones, cell phone adapters, digital cameras, and webcams, all of which can enable remote care. The ability of these devices to identify various ophthalmic diseases has been studied, including cataracts, as well as abnormalities of the ocular adnexa, cornea, and anterior chamber. This article reviews the current state of anterior segment imaging for the purpose of ophthalmic telemedical care.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1887899},
	author = {Armstrong, Grayson W and Kalra, Gagan and De Arrigunaga, Sofia and Friedman, David S and Lorch, Alice C}
}
@article {913391,
	title = {Reevaluation of the Retinal Dystrophy Due to Recessive Alleles of RGR With the Discovery of a Cis-Acting Mutation in CDHR1.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {11},
	year = {2016},
	month = {2016 Sep 1},
	pages = {4806-13},
	abstract = {PURPOSE: Mutation of RGR, encoding retinal G-protein coupled receptor was originally reported in association with retinal dystrophy in 1999. A single convincing recessive variant segregated perfectly in one family of five affected and two unaffected siblings. At least one further individual, homozygous for the same variant has since been reported. The aim of this report was to reevaluate the findings in consideration of data from a whole genome sequencing (WGS) study of a large cohort of retinal dystrophy families. METHODS: Whole genome sequencing was performed on 599 unrelated probands with inherited retinal disease. Detailed phenotyping was performed, including clinical evaluation, electroretinography, fundus photography, fundus autofluorescence imaging (FAF) and spectral-domain optical coherence tomography (OCT). RESULTS: Overall we confirmed that affected individuals from six unrelated families were homozygous for both the reported RGR p.Ser66Arg variant and a nearby frameshifting deletion in CDHR1 (p.Ile841Serfs119*). All had generalized rod and cone dysfunction with severe macular involvement. An additional proband was heterozygous for the same CDHR1/RGR haplotype but also carried a second null CDHR1 mutation on a different haplotype. A comparison of the clinical presentation of the probands reported here with other CDHR1-related retinopathy patients shows the phenotypes to be similar in presentation, severity, and rod/cone involvement. CONCLUSIONS: These data suggest that the recessive retinal disorder previously reported to be due to homozygous mutation in RGR is, at least in part, due to variants in CDHR1 and that the true consequences of RGR knock-out on human retinal structure and function are yet to be determined.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-19687},
	author = {Arno, Gavin and Hull, Sarah and Carss, Keren and Dev-Borman, Arundhati and Chakarova, Christina and Bujakowska, Kinga and van den Born, Ingeborgh and Robson, Anthony G and Holder, Graham E and Michaelides, Michel and Cremers, Frans P M and Pierce, Eric and Raymond, F Lucy and Moore, Anthony T and Webster, Andrew R}
}
@article {284001,
	title = {Successful treatment of Paecilomyces lilacinus keratitis with oral posaconazole},
	journal = {Cornea},
	volume = {33},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {747-9},
	abstract = {PURPOSE: To report a case of successful medical treatment with oral posaconazole in refractory fungal keratitis caused by Paecilomyces lilacinus. METHODS: Case report. RESULTS: A 57-year-old male, soft contact lens wearer presented with irritation, pain, photophobia, and reduced vision. Slit-lamp examination showed a large corneal epithelial defect with a peripheral infiltrate. The patient did not improve on fortified topical antibiotics. After the diagnosis of P. lilacinus fungal keratitis, oral voriconazole and topical antifungal therapy were started. Despite antifungal therapy, progressive disease required therapeutic penetrating keratoplasty. Postoperatively, because of clinical signs of recurrence and in vivo confocal microscopy findings of presumed hyphae in the cornea, intracameral miconazole was injected and oral posaconazole was started. The patient improved and demonstrated no hyphae 6 weeks after starting posaconazole. When posaconazole was stopped, the cornea remained clear with excellent acuity. However, because of acute graft rejection 2 months after stopping posaconazole, keratoprosthesis was implanted, with no evidence of infection at surgery or during the 3.5-year follow-up. CONCLUSIONS: To the best of our knowledge, this is the first report on the use of oral posaconazole for Paecilomyces keratitis. Posaconazole might be indicated in the treatment of refractory Paecilomyces keratitis that is resistant to conventional therapy.},
	keywords = {Administration, Oral, Antifungal Agents, Corneal Ulcer, Eye Infections, Fungal, Humans, Male, Middle Aged, Mycoses, Paecilomyces, Triazoles},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000143},
	author = {Arnoldner, Michael A and Kheirkhah, Ahmad and Jakobiec, Frederick A and Durand, Marlene L and Hamrah, Pedram}
}
@article {1439843,
	title = {VON HIPPEL-LINDAU DISEASE: Update on Pathogenesis and Systemic Aspects},
	journal = {Retina},
	volume = {39},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {2243-2253},
	abstract = {PURPOSE: To provide an update summarizing the biologic pathways governing von Hippel-Lindau (VHL) disease pathogenesis and to provide an overview of systemic manifestations as well as screening recommendations. METHODS: A PubMed search of the English language literature was reviewed using the following search terms: von Hippel-Lindau, von Hippel-Lindau disease, and VHL. Of 6,696 publications, the most current and pertinent information related to the pathogenesis and systemic aspects of VHL disease were included in this review. RESULTS: von Hippel-Lindau disease is one of the most frequently occurring multisystem familial cancer syndromes. The disease results from germline mutation in the VHL tumor suppressor gene on the short arm of chromosome 3. Mutation in the VHL gene affects multiple cellular processes including transcriptional regulation, extracellular matrix formation, apoptosis, and, in particular, the cellular adaptive response to hypoxia. As a result, there is widespread development of vascular tumors affecting the retina, brain, and spine, as well as a spectrum of benign and malignant tumors and/or cysts in visceral organs. CONCLUSION: The ophthalmologist plays a key role in VHL disease diagnosis, as retinal hemangioblastoma is frequently the first disease manifestation. Screening guidelines for individuals with known VHL disease, and those at risk of VHL disease, help to ensure early detection of potentially vision-threatening and life-threatening disease.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002555},
	author = {Aronow, Mary E and Wiley, Henry E and Gaudric, Alain and Krivosic, Valerie and Gorin, Michael B and Shields, Carol L and Shields, Jerry A and Jonasch, Eric W and Singh, Arun D and Chew, Emily Y}
}
@article {1709691,
	title = {Macular Hole in a patient with Pentosan Polysulfate Maculopathy},
	journal = {Retin Cases Brief Rep},
	year = {2023},
	month = {2023 Jun 14},
	abstract = {PURPOSE: Pentosan polysulfate (PPS), a drug used for interstitial cystitis, has recently been detected to cause maculopathy in a dose-dependent manner. Outer retinal atrophy is the hallmark of this condition. METHODS: History, examination and multimodal imaging were used to guide diagnosis and management. RESULTS: We report a case of PPS-related maculopathy in a 77-year-old lady, who presented with florid retinal atrophy at the posterior pole in both eyes, and a concurrent macular hole in the left eye. She had been diagnosed with interstitial cystitis several years prior for which she was prescribed PPS (Elmiron). She had noticed a drop in vision 5 years following initiation of PPS and self-discontinued the drug after 24 years of use. A diagnosis of PPS-related maculopathy with a macular hole was made. She was counselled regarding the prognosis and was advised to avoid PPS. Surgery for macular hole was deferred in view of the severe retinal atrophy. CONCLUSIONS: PPS-related maculopathy can lead to severe retinal atrophy and a subsequent degenerative macular hole. A high index of suspicion is required for early detection and cessation of drug to prevent this irreversible vision loss.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001444},
	author = {Arora, Neha and Hoyek, Sandra and Patel, Nimesh A}
}
@article {1573101,
	title = {A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies},
	journal = {Pharmaceuticals (Basel)},
	volume = {14},
	number = {1},
	year = {2021},
	month = {2021 Jan 11},
	abstract = {We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients{\textquoteright} needs.},
	issn = {1424-8247},
	doi = {10.3390/ph14010050},
	author = {Arranz-Romera, Alicia and Hernandez, Maria and Checa-Casalengua, Patricia and Garcia-Layana, Alfredo and Molina-Martinez, Irene T and Recalde, Sergio and Young, Michael J and Tucker, Budd A and Herrero-Vanrell, Roc{\'\i}o and Fernandez-Robredo, Patricia and Bravo-Osuna, Irene}
}
@article {1580507,
	title = {Rapid reduction of macular edema due to retinal vein occlusion with low-dose normobaric hyperoxia},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {259},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {2113-2118},
	abstract = {PURPOSE: We investigated the effects of a relatively inexpensive, non-invasive, short-term treatment with low-dose normobaric hyperoxia (NBH) on macular edema in patients with retinal vein occlusion (RVO). METHODS: Participants with macular edema associated with RVO were treated with 5 LPM of NBH via facemask (40\% fraction of inspired oxygen, FIO2) for 3 h. Patients with non-fovea involving edema who elected to be observed returned for a second treatment 1 month later to test reproducibility. RESULTS: A 3-h session of NBH (n = 45) resulted in decreased maximum macular thickness (MMT) (mean 7.10\%, t34=9.63 P\&lt;.001) and central macular thickness (CMT) (mean 4.64\%, t34=6.90, P\&lt;.001) when compared to untreated eyes with RVO measured over the same period of time (n = 12) or their healthy fellow eye (n = 34; MMT:t34=-9.60, P\&lt;.001;CMT: t34=-6.72, P\&lt;.001). Patients who had a second NBH treatment 1 month later experienced a recurrence of their edema, but demonstrated a similar significant reduction in MMT and CMT after the second NBH treatment. CONCLUSIONS: Three-hour treatment with 40\% FIO2 NBH results in a significant reduction in MMT and CMT. This study supports an ischemic mechanism for macular edema associated with retinal vein occlusion. TRANSLATIONAL RELEVANCE: Short-term low-dose normobaric hyperoxia is a simple, inexpensive, and ubiquitous treatment that may provide an alternate or adjunctive approach to treating macular edema in patients who are resistant to or cannot afford anti-VEGF medications.},
	keywords = {Humans, Hyperoxia, Intravitreal Injections, Macular Edema, Reproducibility of Results, Retinal Vein Occlusion, Tomography, Optical Coherence, Treatment Outcome, Visual Acuity},
	issn = {1435-702X},
	doi = {10.1007/s00417-021-05128-w},
	author = {Arroyo, Jorge G and Seto, Brendan and Yamada, Keiko and Zeng, Ke and Minturn, Robert and Lemire, Colin A}
}
@article {1658655,
	title = {Retraction Note to: Rapid reduction of macular edema due to retinal vein occlusion with low-dose normobaric hyperoxia},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {261},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {289},
	issn = {1435-702X},
	doi = {10.1007/s00417-022-05889-y},
	author = {Arroyo, Jorge G and Seto, Brendan and Yamada, Keiko and Zeng, Ke and Minturn, Robert and Lemire, Colin A}
}
@article {1351135,
	title = {Factors predictive of remission of new-onset anterior uveitis},
	journal = {Ophthalmology},
	volume = {121},
	number = {3},
	year = {2014},
	month = {2014 Mar},
	pages = {778-84},
	abstract = {PURPOSE: To identify factors predictive of remission of inflammation in new-onset anterior uveitis cases treated at tertiary uveitis care facilities.

DESIGN: Retrospective cohort study.

PARTICIPANTS: Patients seeking treatment at participating academic uveitis clinics within 90 days of initial diagnosis of anterior uveitis.

METHODS: Retrospective cohort study based on standardized chart review.

MAIN OUTCOME MEASURES: Factors predictive of remission (no disease activity without corticosteroid or immunosuppressive treatments at all visits during a 90-day period).

RESULTS: Nine hundred ninety eyes (687 patients) had a first-ever diagnosis of anterior uveitis within 90 days before initial presentation and had follow-up visits thereafter. The median follow-up time was 160 days. Systemic diagnoses with juvenile idiopathic arthritis (JIA; adjusted hazard ratio [aHR], 0.38; 95\% confidence interval [CI], 0.19-0.74) and Beh{\c c}et{\textquoteright}s disease (aHR, 0.10; 95\% CI, 0.01-0.85) were associated with a lower incidence of uveitis remission. Cases of bilateral uveitis (aHR, 0.68; 95\% CI, 0.54-0.87) and those with a history of cataract surgery before presentation (aHR, 0.51; 95\% CI, 0.29-0.87) also had a lower incidence of remission. Regarding clinical findings at the initial visit, a high degree of vitreous cells at initial presentation was associated with a lower incidence of remission (for 1+ or more vs. none: aHR, 0.72; 95\% CI, 0.55-0.95). An initial visual acuity of 20/200 or worse, with respect to 20/40 or better, also was predictive of a lower incidence of remission (aHR, 0.52; 95\% CI, 0.32-0.86).

CONCLUSIONS: Factors associated with a lower incidence of remission among new-onset anterior uveitis cases included diagnosis with JIA, Beh{\c c}et{\textquoteright}s disease, bilateral uveitis, history of cataract surgery, findings of 1+ or more vitreous cells at presentation, and an initial visual acuity of 20/200 or worse. Patients with these risk factors seem to be at higher risk of persistent inflammation; reciprocally, patients lacking these factors would be more likely to experience remission. Patients with risk factors for nonremission of uveitis should be managed taking into account the higher probability of a chronic inflammatory course.},
	keywords = {Adult, Arthritis, Juvenile, Behcet Syndrome, Cataract Extraction, Cohort Studies, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Remission, Spontaneous, Retrospective Studies, Risk Factors, Uveitis, Anterior, Visual Acuity, Vitreous Body},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2013.09.041},
	author = {Artornsombudh, Pichaporn and Pistilli, Maxwell and Foster, C Stephen and Pujari, Siddharth S and Gangaputra, Sapna S and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Suhler, Eric B and Thorne, Jennifer E and Kempen, John H}
}
@article {1471000,
	title = {ISOPT Hot Topic Panel Discussion on Cornea Anterior Segment Disease},
	journal = {J Ocul Pharmacol Ther},
	volume = {35},
	number = {8},
	year = {2019},
	month = {2019 Oct},
	pages = {447-456},
	abstract = {The cornea and its adnexa pose a unique situation of a tightly defined set of requirements for its function. This includes: transparency, perfect built to obtain appropriate refractive power, protective barrier from microbial invaders. Moreso, the cornea also endures extreme external physical conditions (temperature, high and low humidity, winds and alike). All these functions are maintained while preserving a constant state of homogenous wetting. Toward that end the cornea is equipped with an elaborated network of sensory neural network. While enabling the blinking reflex and maintaining the physiological steady state of wetting, this neural network also makes the cornea prone to the discomfort that with or without associated changes seen on medical examination. ISOPT Clinical 2018 discussion touched upon this hypercomplex situation, addressing the role of inflammation and its resulting discomfort in dry eye conditions. The discussion also engulfed the emerging neuropathic pain syndrome that is recently gaining more attention. Another related topic was the utilization of autologous serum tears and its ability to provide amelioration to desperate patients. Finally, the panel discussed the issue of treating corneal infection, including when and how to utilize steroids in the course of therapy. We assume the reader will find interest in this discussion that directly addresses issues seen day in and day out in our busy clinics.},
	issn = {1557-7732},
	doi = {10.1089/jop.2019.0023},
	author = {Asbell, Penny A and Aquavella, James V and Hamrah, Pedram and Pepose, Jay S and Rose, Linda and Ucakhan, Omur}
}
@article {1263296,
	title = {Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis},
	journal = {Eur J Hum Genet},
	volume = {25},
	number = {11},
	year = {2017},
	month = {2017 Nov},
	pages = {1261-1267},
	abstract = {Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95\% confidence interval: 1.18 (1.14-1.21), P=1.8 {\texttimes} 10-27) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5\%, P=2.1 {\texttimes} 10-5); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.},
	issn = {1476-5438},
	doi = {10.1038/ejhg.2017.136},
	author = {Aschard, Hugues and Kang, Jae H and Iglesias, Adriana I and Hysi, Pirro and Cooke Bailey, Jessica N and Khawaja, Anthony P and Allingham, R Rand and Ashley-Koch, Allison and Lee, Richard K and Moroi, Sayoko E and Brilliant, Murray H and Wollstein, Gadi and Schuman, Joel S and Fingert, John H and Budenz, Donald L and Realini, Tony and Gaasterland, Terry and Scott, William K and Singh, Kuldev and Sit, Arthur J and Igo, Robert P and Song, Yeunjoo E and Hark, Lisa and Ritch, Robert and Rhee, Douglas J and Gulati, Vikas and Haven, Shane and Vollrath, Douglas and Zack, Donald J and Medeiros, Felipe and Weinreb, Robert N and Cheng, Ching-Yu and Chasman, Daniel I and Christen, William G and Pericak-Vance, Margaret A and Liu, Yutao and Kraft, Peter and Richards, Julia E and Rosner, Bernard A and Hauser, Michael A and International Glaucoma Genetics Consortium and Klaver, Caroline C W and van Duijn, Cornelia M and Haines, Jonathan and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1635624,
	title = {Hemi- and Central Retinal Vein Occlusion Associated with COVID-19 Infection in Young Patients without Known Risk Factors},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {6},
	year = {2022},
	month = {2022 Jun},
	pages = {520-530},
	abstract = {PURPOSE: Venous thromboembolic complications have been reported in association with coronavirus disease 2019 (COVID-19) infection. We raised awareness regarding a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO). DESIGN: Multicenter, retrospective, nonconsecutive case series. SUBJECTS: Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection, were included. The exclusion criteria were as follows: age \&gt;50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. METHODS: This was a multicenter, retrospective, nonconsecutive case series including patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection. The exclusion criteria were as follows: age \&gt;50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. MAIN OUTCOME MEASURES: Ophthalmic findings, including presenting and final visual acuity (VA), imaging findings, and clinical course. RESULTS: Twelve eyes of 12 patients with CRVO (9 of 12) or HRVO (3 of 12) after COVID-19 infection were included. The median age was 32 years (range, 18-50 years). Three patients were hospitalized, but none were intubated. The median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. The presenting VA ranged from 20/20 to counting fingers, with over half (7 of 12) having a VA of >=20/40. OCT revealed macular edema in 42\% of the eyes; of these, 80\% (4 of 5) were treated with anti-VEGF injections. Ninety-two percent (11 of 12) had partial or complete resolution of ocular findings at final follow-up. Four eyes (33\%) had retinal thinning, as determined using OCT, by the end of the study interval. The final VA ranged from 20/20 to 20/60, with 11 of the 12 (92\%) eyes achieving a VA of >=20/40 at a median final follow-up period of 13 weeks (range, 4-52 weeks). CONCLUSIONS: Although we acknowledge the high seroprevalence of COVID-19 and that a causal relationship cannot be established, we reported this series to raise awareness regarding the potential risk of retinal vascular events due to a heightened thromboinflammatory state associated with COVID-19 infection.},
	keywords = {Adult, COVID-19, COVID-19 Testing, Glaucoma, Humans, Hypertension, Middle Aged, Obesity, Retinal Vein Occlusion, Retrospective Studies, Risk Factors, Seroepidemiologic Studies},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.02.004},
	author = {Ashkenazy, Noy and Patel, Nimesh A and Sridhar, Jayanth and Yannuzzi, Nicolas A and Belin, Peter J and Kaplan, Richard and Kothari, Nikisha and Benitez Bajandas, Gabriel A and Kohly, Radha P and Roizenblatt, Roberto and Pinhas, Alexander and Mundae, Rusdeep and Rosen, Richard B and Ryan, Edwin H and Chiang, Allen and Chang, Louis K and Khurana, Rahul N and Finn, Avni P}
}
@article {1522741,
	title = {Characterization of non-linear mechanical behavior of the cornea},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Jul 14},
	pages = {11549},
	abstract = {The objective of this study was to evaluate which hyperelastic model could best describe the non-linear mechanical behavior of the cornea, in order to characterize the capability of the non-linear model parameters to discriminate structural changes in a damaged cornea. Porcine corneas were used, establishing two different groups: control (non-treated) and NaOH-treated (damaged) corneas (n = 8). NaOH causes a chemical burn to the corneal tissue, simulating a disease associated to structural damage of the stromal layer. Quasi-static uniaxial tensile tests were performed in nasal-temporal direction immediately after preparing corneal strips from the two groups. Three non-linear hyperelastic models (i.e. Hamilton-Zabolotskaya model, Ogden model and Mooney-Rivlin model) were fitted to the stress-strain curves obtained in the tensile tests and statistically compared. The corneas from the two groups showed a non-linear mechanical behavior that was best described by the Hamilton-Zabolotskaya model, obtaining the highest coefficient of determination (R \&gt; 0.95). Moreover, Hamilton-Zabolotskaya model showed the highest discriminative capability of the non-linear model parameter (Parameter A) for the tissue structural changes between the two sample groups (p = 0.0005). The present work determines the best hyperelastic model with the highest discriminative capability in description of the non-linear mechanical behavior of the cornea.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-68391-7},
	author = {Ashofteh Yazdi, A and Melchor, J and Torres, J and Faris, I and Callejas, A and Gonzalez-Andrades, M and Rus, G}
}
@article {1651353,
	title = {Epigenetic Regulation of Optic Nerve Development, Protection, and Repair},
	journal = {Int J Mol Sci},
	year = {2022},
	author = {Ashok, A and Pooranawattanakul, S and Tai, WL and Cho, KS and Utheim, T P and Cestari, DM and Chen, D F}
}
@article {1748451,
	title = {Electrical stimulation alters DNA methylation and promotes neurite outgrowth},
	journal = {J Cell Biochem},
	volume = {124},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {1530-1545},
	abstract = {Electrical stimulation (ES) influences neural regeneration and functionality. We here investigate whether ES regulates DNA demethylation, a critical epigenetic event known to influence nerve regeneration. Retinal ganglion cells (RGCs) have long served as a standard model for central nervous system neurons, whose growth and disease development are reportedly affected by DNA methylation. The current study focuses on the ability of ES to rescue RGCs and preserve vision by modulating DNA demethylation. To evaluate DNA demethylation pattern during development, RGCs from mice at different stages of development, were analyzed using qPCR for ten-eleven translocation (TETs) and immunostained for 5 hydroxymethylcytosine (5hmc) and 5 methylcytosine (5mc). To understand the effect of ES on neurite outgrowth and DNA demethylation, cells were subjected to ES at 75 {\textmu}Amp biphasic ramp for 20 min and cultured for 5 days. ES increased TETs mediated neurite outgrowth, DNA demethylation, TET1 and growth associated protein 43 levels significantly. Immunostaining of PC12 cells following ES for histone 3 lysine 9 trimethylation showed cells attained an antiheterochromatin configuration. Cultured mouse and human retinal explants stained with β-III tubulin exhibited increased neurite growth following ES. Finally, mice subjected to optic nerve crush injury followed by ES exhibited improved RGCs function and phenotype as validated using electroretinogram and immunohistochemistry. Our results point to a possible therapeutic regulation of DNA demethylation by ES in neurons.},
	issn = {1097-4644},
	doi = {10.1002/jcb.30462},
	author = {Ashok, Ajay and Tai, Wai Lydia and Lennikov, Anton and Chang, Karen and Chen, Julie and Li, Boyuan and Cho, Kin-Sang and Utheim, Tor Paaske and Chen, Dong Feng}
}
@article {1667714,
	title = {Using Ultrawide Field-Directed Optical Coherence Tomography for Differentiating Nonproliferative and Proliferative Diabetic Retinopathy},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {7},
	abstract = {PURPOSE: To evaluate the ability of ultrawide field (UWF)-directed optical coherence tomography (OCT) to detect retinal neovascularization in eyes thought to have severe nonproliferative diabetic retinopathy (NPDR). METHODS: Retrospective study of 20 consecutive patients diagnosed with severe NPDR by clinical examination. All patients underwent UWF color imaging (UWF-CI) and UWF-directed OCT following a prespecified imaging protocol to assess the mid periphery, 15/32 (46.9\%) eyes underwent UWF-fluorescein angiography (FA). On OCT, new vessels elsewhere (NVE) were defined when vessels breached the internal limiting membrane. RESULTS: A total of 32 eyes of 20 patients were evaluated. Of the 45 suspected areas of intraretinal microvascular abnormalities (IRMA) on UWF-CI, 38 (84.4\%) were imaged by UWF-directed OCT, and 9/38 IRMA (23.7\%) were NVE by OCT. Furthermore, UWF-directed OCT identified seven additional NVE in three eyes not seen on UWF-CI. This resulted in a change in diabetic retinopathy (DR) severity from severe NPDR to PDR in 8/32 eyes (25.0\%). Among the 46.9\% of eyes with UWF-FA, UWF-directed OCT agreed with the UWF-FA findings in 80\% (12/15 eyes), missing only one peripheral NVE outside the UWF-OCT scanning area. Two eyes had subtle NVD that were not evident on UWF-directed OCT. CONCLUSIONS: This pilot study suggests that UWF-directed OCT may help differentiate IRMA from NVE and detect unrecognized NVE in eyes with advanced DR in a clinical practice setting. Future prospective studies in larger cohorts could determine whether this rapid and noninvasive method is clinically relevant in determining NVE presence or retinopathy progression and complication risk. TRANSLATIONAL RELEVANCE: UWF-directed OCT may offer a noninvasive alternative to detect NVE in eyes with DR.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Humans, Pilot Projects, Prospective Studies, Retinal Diseases, Retinal Vessels, Retrospective Studies, Tomography, Optical Coherence},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.2.7},
	author = {Ashraf, Mohamed and Sun, Jennifer K and Silva, Paolo S and Aiello, Lloyd Paul}
}
@article {1698296,
	title = {Dysregulation of DNA repair genes in Fuchs endothelial corneal dystrophy},
	journal = {Exp Eye Res},
	volume = {231},
	year = {2023},
	month = {2023 Jun},
	pages = {109499},
	abstract = {Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet{\textquoteright}s membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (\&gt;40) or non-expanded (\&lt;40) intronic CTG repeats in TCF4 gene and from age-matched normal donors. Change in mRNA expression of \&lt;0.5- or \&gt;2.0-fold in FECD relative to normal was set as cutoff for down- or upregulation. Downregulated mitochondrial genes were further validated using the UVA-based mouse model of FECD. FECD specimens exhibited downregulation of 9 genes and upregulation of 8 genes belonging to the four major DNA repair pathways, namely, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double strand break (DSB) repair, compared to normal donors. MMR gene MSH2 and BER gene POLB were preferentially upregulated in expanded FECD. BER genes LIG3 and NEIL2, DSB repair genes PARP3 and TOP3A, NER gene XPC, and unclassified pathway gene TREX1, were downregulated in both expanded and non-expanded FECD. MtDNA repair genes, Lig3, Neil2, and Top3a, were also downregulated in the UVA-based mouse model of FECD. Our findings identify impaired DNA repair pathways that may play an important role in DNA damage due to oxidative stress as well as genetic predisposition noted in FECD.},
	keywords = {Animals, DNA Glycosylases, DNA Repair, DNA, Mitochondrial, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Genetic Predisposition to Disease, Humans, Mice},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2023.109499},
	author = {Ashraf, Shazia and Deshpande, Neha and Vasanth, Shivakumar and Melangath, Geetha and Wong, Raymond J and Zhao, Yan and Price, Marianne O and Price, Francis W and Jurkunas, Ula V}
}
@article {1532346,
	title = {Retinal Vascular Caliber Association with Nonperfusion and Diabetic Retinopathy Severity Depends on Vascular Caliber Measurement Location},
	journal = {Ophthalmol Retina},
	volume = {5},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {571-579},
	abstract = {PURPOSE: To evaluate the association of retinal nonperfusion and diabetic retinopathy (DR) severity with location of vascular caliber measurement using ultrawide field (UWF) imaging. DESIGN: Retrospective image review. PARTICIPANTS: Adults with diabetes mellitus. METHODS: All images from subjects with same-day UWF fluorescein angiography (FA) and color imaging were evaluated. Predominantly peripheral lesions (PPL) and DR severity were graded from UWF color images. Nonperfusion was quantified using UWF-FA in defined retinal regions [posterior pole (PP), mid-periphery (MP), far-periphery (FP)]. Retinal vessel calibers were measured at an optic disc centered inner and outer zone. MAIN OUTCOME MEASURES: Nonperfusion index (NPI) in the PP, MP and FP. Mean arteriole and venule diameter in the inner and outer zones. RESULTS: Two hundred eighty-five eyes of 193 patients (24.9\% mild nonproliferative DR [NPDR], 22.8\% moderate NPDR, 37.5\% severe NPDR and 14.7\% proliferative DR [PDR]) were reviewed. No significant associations between inner zone arteriolar diameter and retinal NPI overall or in any retinal region. In the outer zone, eyes with thinnest arteriolar calibers (quartile 1) were associated with a 1.7- to 2.4-fold nonperfusion increase across all retinal regions compared to the remaining eyes (P = 0.002 [PP] to 0.048 [FP]). In the outer zone, the percentage of eyes in the thinnest quartile of retinal arteriolar diameter increased with worsening DR severity (mild NPDR: 10\% vs PDR: 31\%, P = 0.007). This association was not observed when measured within the inner zone (P\&nbsp;= 0.129). All venular caliber associations were not statistically significant when corrected for potentially confounding factors. Thinner outer zone retinal arteriolar caliber (quartile 1) was more common in eyes with PPL compared to eyes without PPL (34.1\% vs 20.8\%, P = 0.017) as were thicker outer venular calibers (quartile 4) (33\% vs 21.3\%, P = 0.036). Presence of PPL was associated with thinner outer zone arteriolar caliber (109.7\&nbsp;{\textpm}\&nbsp;26.5μm vs 123.0 {\textpm} 29.5μm, P = 0.001). CONCLUSIONS: The association of vascular caliber with nonperfusion and DR severity differs based upon the retinal location at which vascular caliber is measured. Peripheral arterial narrowing is associated with increasing nonperfusion, worsening DR severity and presence of PPL. In contrast, inner zone retinal arteriolar caliber is not associated with these findings.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2020.09.003},
	author = {Ashraf, Mohamed and Shokrollahi, Siamak and Pisig, Alex U and Sampani, Konstantina and AbdelAl, Omar and Cavallerano, Jerry D and Robertson, Gavin and Fleming, Alan and van Hemert, Jano and Pitoc, Cloyd M and Sun, Jennifer K and Aiello, Lloyd Paul and Silva, Paolo S}
}
@article {1490435,
	title = {Disparity of microaneurysm count between ultrawide field colour imaging and ultrawide field fluorescein angiography in eyes with diabetic retinopathy},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {1762-1767},
	abstract = {AIMS: To compare microaneurysm (MA) counts using ultrawide field colour images (UWF-CI) and ultrawide field fluorescein angiography (UWF-FA). METHODS: Retrospective study including patients with type 1 or 2 diabetes mellitus receiving UWF-FA and UWF-CI within 2 weeks. MAs were manually counted in individual Early Treatment Diabetic Retinopathy Study (ETDRS) and extended UWF zones. Fields with MAs >=20 determined diabetic retinopathy (DR) severity (0 fields=mild, 1-3=moderate, >=4=severe). UWF-FA and UWF-CI agreement was determined and UWF-CI DR severity sensitivity analysis adjusting for UWF-FA MA counts performed. RESULTS: In 193 patients (288 eyes), 2.4\% had no DR, 29.9\% mild non-proliferative DR (NPDR), 32.6\% moderate (NPDR), 22.9\% severe NPDR and 12.2\% proliferative DR. UWF-FA MA counts were 3.5-fold higher (p\&lt;0.001) than UWF-CI counts overall, 3.2x-fold higher in ETDRS fields (p\&lt;0.001) and 5.3-fold higher in extended ETDRS fields (p\&lt;0.001) and higher in type 1 versus type 2 diabetes (p\&lt;0.001). In eyes with NPDR on UWF-CI (n=246), UWF-FA images had 1.6x-3.5x more fields with >=20 MAs (p\&lt;0.001). Fair agreement existed between imaging modalities (k=0.221-0.416). In ETDRS fields, DR severity agreement increased from k=0.346 to 0.600 when dividing UWF-FA counts by a factor of 3, followed by rapid decline in agreement thereafter. Total UWF area agreement increased from k=0.317 to 0.565 with an adjustment factor of either 4 or 5. CONCLUSIONS: UWF-FA detects threefold to fivefold more MAs than UWF-CI and identifies 1.6-3.5-fold more fields affecting DR severity. Differences exist at all DR severity levels, thus limiting direct comparison between the modalities. However, correcting UWF-FA MA counts substantially improves DR severity agreement between the modalities.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-315807},
	author = {Ashraf, Mohamed and Sampani, Konstantina and AbdelAl, Omar and Fleming, Alan and Cavallerano, Jerry and Souka, Ahmed and El Baha, Samir Mohamed and Silva, Paolo S and Sun, Jennifer and Aiello, Lloyd Paul}
}
@article {1598048,
	title = {Factors Affecting Predominantly Peripheral Lesion Identification and Grading},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {7},
	year = {2021},
	month = {2021 06 01},
	pages = {6},
	abstract = {Purpose: The purpose of this study was to determine factors affecting predominantly peripheral lesion (PPL) grading, such as qualitative versus quantitative assessment, device type, and severity of diabetic retinopathy (DR) in ultrawide field color images (UWF-CIs). Methods: Patients with DR had UWF-CI qualitatively graded for PPL using standardized techniques and had hemorrhages/microaneurysms (H/Mas) individually annotated for quantitative PPL grading on two different ultrawide field devices. Results: Among 791 eyes of 481 patients, 38.2\% had mild nonproliferative DR (NPDR), 34.7\% had moderate NPDR, and 27.1\% had severe NPDR to proliferative DR (PDR). The overall agreement between qualitative and quantitative PPL grading was moderate (k = 0.423, P \&lt; 0.001). Agreement rates were fair in eyes with mild NPDR (k = 0.336, P \&lt; 0.001) but moderate in eyes with moderate NPDR (k = 0.525, P \&lt; 0.001) and severe NPDR-PDR (k = 0.409, P \&lt; 0.001). Increasing thresholds for quantitative PPL determination improved agreement rates, with peak agreements at H/Ma count differences of six for mild NPDR, five for moderate NPDR, and nine for severe NPDR-PDR. Based on ultrawide field device type (California = 412 eyes vs. 200Tx = 379 eyes), agreement between qualitative and quantitative PPL grading was moderate for all DR severities in both devices (k = 0.369-0.526, P \&lt; 0.001) except for mild NPDR on the 200Tx, which had poor agreement (k = 0.055, P = 0.478). Conclusions: Determination of PPL varies between standard qualitative and quantitative grading and is dependent on NPDR severity, device type, and magnitude of lesion differences used for quantitative assessment. Translational Relevance: Prior UWF studies have not accounted for imaging and grading factors that affect PPL, such factors need to be reviewed when assessing thresholds for DR progression rates.},
	keywords = {Diabetic Retinopathy, Eye, Humans, Microaneurysm, Severity of Illness Index},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.7.6},
	author = {Ashraf, Mohamed and Rageh, Abdulrahman and Gilbert, Michael and Tolls, Dorothy and Fleming, Alan and Souka, Ahmed and El-Baha, Samir and Cavallerano, Jerry D and Sun, Jennifer K and Aiello, Lloyd Paul and Silva, Paolo S}
}
@article {1498252,
	title = {Diabetic retinopathy and ultrawide field imaging},
	journal = {Semin Ophthalmol},
	volume = {35},
	number = {1},
	year = {2020},
	month = {2020 Jan 02},
	pages = {56-65},
	abstract = {The introduction of ultrawide field imaging has allowed the visualization of approximately 82\% of the total retinal area compared to only 30\% using 7-standard field Early Treatment Diabetic Retinopathy (ETDRS) photography. This substantially wider field of view, while useful in many retinal vascular diseases, is particularly important in diabetic retinopathy where eyes with predominantly peripheral lesions or PPL have been shown to have significantly greater progression rates compared to eyes without PPL. In telemedicine settings, ultrawide field imaging has substantially reduced image ungradable rates and increased rate of disease identification allowing care to be delivered more effectively. Furthermore, the use of ultrawide field fluorescein angiography allows the visualization of significantly more diabetic retinal lesions and allows more accurate quantification of total retinal nonperfusion, with potential implications in the management of diabetic retinopathy and diabetic macular edema. The focus of this paper is to review the current role of ultrawide field imaging in diabetic retinopathy and its possible future role in innovations for retinal image analysis such as artificial intelligence and vessel caliber measurements.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1729818},
	author = {Ashraf, Mohamed and Shokrollahi, Siamak and Salongcay, Recivall P and Aiello, Lloyd Paul and Silva, Paolo S}
}
@article {1661848,
	title = {Comparison of Widefield Laser Ophthalmoscopy and ETDRS Retinal Area for Diabetic Retinopathy},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {4},
	year = {2022},
	month = {2022 Dec},
	pages = {100190},
	abstract = {PURPOSE: To evaluate agreement of nonmydriatic confocal scanning laser ophthalmoscopy (SLO; EIDON [CenterVue]) and the 7-standard field ETDRS area on ultrawide-field (UWF) SLO imaging for identification of diabetic retinopathy (DR) severity. DESIGN: Single-site, prospective, comparative, instrument validation study. PARTICIPANTS: One hundred ten eyes of 55 patients with diabetes mellitus were evaluated. METHODS: Each patient underwent nonmydriatic, nonsimultaneous stereoscopic imaging using the EIDON camera and 4 fields of 60{\textdegree}\&nbsp;{\texttimes} 55{\textdegree} were acquired (macula centered, disc centered, temporal macula, superotemporal). Mydriatic UWF retinal images were acquired using a nonsimultaneous stereographic protocol with UWF imaging (California; Optos plc). Before grading, a standardized ETDRS 7-field image mask was applied to all UWF retinal images. Images from each device were graded independently by 2 masked graders using the ETDRS clinical DR classification. Any discrepancy in DR grading between the devices was adjudicated by a third grader. MAIN OUTCOME MEASURES: κ Levels of agreement, sensitivity, and specificity for DR thresholds. RESULTS: Severity by ETDRS grading was as follows: no DR, 10.9\%; mild nonproliferative DR (NPDR), 45.5\%; moderate NPDR, 16.5\%; severe NPDR, 11.8\%; proliferative DR, 12.7\%; high-risk proliferative DR, 2.7\%; and ungradable, 0\%. After adjudication, the level of DR identified on EIDON images agreed exactly with that of UWF ETDRS imaging in 87\% of eyes (n\&nbsp;= 96) and was within 1 step in 99.1\% of eyes (n\&nbsp;= 109) with a simple κ value of 0.8244 {\textpm} 0.0439 (95\% confidence interval [CI], 0.7385-0.9104) and weighted (linear) κ value of 0.9041 {\textpm} 0.0257 (95\% CI, 0.8537-0.9545). Sensitivity and specificity compared with ETDRS field grading for any DR were 0.96 and 0.75, for moderate NPDR or worse were 0.96 and 0.97, and for severe NPDR or worse were 0.91 and 1.00, respectively. CONCLUSIONS: Nonmydriatic 4-field stereoscopic widefield imaging using the EIDON device was comparable with the DR severity identified within the ETDRS 7-standard field area of UWF images. Future studies will need to evaluate the applicability of this device as a clinical and research tool and the impact of different widefield coverage areas.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100190},
	author = {Ashraf, Mohamed and Hock, Kristen M and Cavallerano, Jerry D and Wang, Frank L and Silva, Paolo S}
}
@article {1538330,
	title = {Interaction Between the Distribution of Diabetic Retinopathy Lesions and the Association of Optical Coherence Tomography Angiography Scans With Diabetic Retinopathy Severity},
	journal = {JAMA Ophthalmol},
	volume = {138},
	number = {12},
	year = {2020},
	month = {2020 Dec 01},
	pages = {1291-1297},
	abstract = {Importance: Studies have not yet determined whether the distribution of lesions in the retinal periphery alters the association between the severity of diabetic retinopathy (DR) and macular vessel density. Objective: To evaluate the association of DR lesion distribution with optical coherence tomography angiography (OCTA) metrics and DR severity. Design, Setting, and Participants: This cross-sectional observational study was conducted at a tertiary care center for diabetic eye disease among 225 patients with type 1 or 2 diabetes who had undergone imaging between February 15, 2016, and December 31, 2019. Exposures: Optical coherence tomography angiography 3 {\texttimes} 3-mm macular scans and ultra-widefield color imaging. Main Outcomes and Measures: Optical coherence tomography angiography vessel density in the superficial capillary plexus, intermediate capillary plexus, and deep capillary plexus and choriocapillaris flow density. The severity of DR and the predominantly peripheral lesions (PPL) were evaluated from ultra-widefield color imaging. Results: The study evaluated 352 eyes (225 patients; 125 men [55.6\%]; mean [SD] age, 52.1 [15.1] years), of which 183 eyes (52.0\%) had mild nonproliferative diabetic retinopathy (NPDR), 71 eyes (20.2\%) had moderate NPDR, and 98 eyes (27.8\%) had severe NPDR or proliferative diabetic retinopathy (PDR). In eyes with no PPL (209 [59.4\%]), the mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 38.1\% [4.7\%]; moderate NPDR, 36.4\% [4.6\%]; severe NPDR or PDR, 34.1\% [4.1\%]; P \&lt; .001) and the deep capillary plexus (mild NPDR, 45.8\% [3.0\%]; moderate NPDR, 45.8\% [2.2\%]; severe NPDR or PDR, 44.5\% [1.9\%]; P = .002), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 69.7\% [6.2\%]; moderate NPDR, 67.6\% [5.6\%]; severe NPDR or PDR, 67.1\% [5.6\%]; P = .01), decreased with increasing DR severity. These associations remained statistically significant even after correcting for age, signal strength index, spherical equivalent, duration of diabetes, type of diabetes, and correlation between eyes of the same patient. In eyes with PPL (143 [40.6\%]), mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 34.1\% [4.1\%]; moderate NPDR, 35.2\% [4.1\%]; severe NPDR or PDR, 36.0\% [4.3\%]; P = .42) and the deep capillary plexus (mild NPDR, 44.5\% [1.7\%]; moderate NPDR, 45.4\% [1.4\%]; severe NPDR or PDR, 44.9\% [1.5\%]; P = .81), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 67.1\% [5.6\%]; moderate NPDR, 69.3\% [4.6\%]; severe NPDR or PDR, 68.3\% [5.6\%]; P = .49), did not appear to change with increasing DR severity. Conclusions and Relevance: These results suggest that central retinal vessel density is associated with DR severity in eyes without, but not with, PPL. These findings suggest a potential need to stratify future optical coherence tomography angiography studies of eyes with DR by the presence or absence of PPL. If DR onset and worsening are associated with the location of retinal nonperfusion, assessment of global retinal nonperfusion using widefield angiography may improve the ability to evaluate DR severity and risk of DR worsening over time.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.4516},
	author = {Ashraf, Mohamed and Sampani, Konstantina and Rageh, Abdulrahman and Silva, Paolo S and Aiello, Lloyd Paul and Sun, Jennifer K}
}
@article {1664972,
	title = {Evaluation of diabetic retinopathy severity on ultrawide field colour images compared with ultrawide fluorescein angiograms},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {534-539},
	abstract = {PURPOSE: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) diabetic retinopathy (DR) severity on ultrawide field (UWF) colour imaging (CI) and UWF fluorescein angiography (FA). DESIGN: Cross-sectional retrospective review. SUBJECTS: Patients with diabetes mellitus and at least mild non-proliferative DR on UWF-CI. METHODS: UWF-CI and UWF-FA images acquired within 1 month of each other were evaluated independently using ETDRS DR Severity Scale (DRSS) for colour photography adapted for UWF-CI and UWF-FA. Extent of non-perfusion (NP, mm2) was determined from UWF-FA images. MAIN OUTCOME MEASURES: Agreement rate between DRSS on UWF-CI and UWF-FA. RESULTS: Images from 218 eyes of 137 patients with diabetes were evaluated. Agreement rate for DRSS between UWF-CI and UWF-FA was moderate to substantial (K=0.46, Kw=0.65). Over-all, DRSS was worse in 73 (33.5\%) eyes on UWF-FA and in 16 (7.3\%) on UWF-CI. Compared to UWF-CI, UWF-FA identified more severe DRSS in 26.5\% (1 step) and 7.34\% (>=2 steps) of eyes. DRSS was worse than UWF-FA in 56 (51.4\%) in early DR (ETDRS levels 20-47, N=109) and 17 (15.6\%) in eyes with severe DR (53 and higher, N=109). In this cohort, the extent of NP significantly increased as eyes approach moderate non-proliferative DR (levels 43-47, p=0.0065). CONCLUSION: When evaluating UWF-FA images using the ETDRS colour severity scale, DRSS is graded as more severe in a substantial number of eyes than when evaluating UWF-CI. It is uncertain how the DRSS levels using UWF-FA translate to clinical outcomes, but the additional lesions detected might provide added prognostic value. These and other recent data emphasise the need of obtaining outcome data based on UWF-FA and the potential need to develop DRSS specifically tailored for UWF-FA images.},
	keywords = {Color, Cross-Sectional Studies, Diabetes Mellitus, Diabetic Retinopathy, Fluorescein Angiography, Fluoresceins, Humans, Photography},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-322163},
	author = {Ashraf, Mohamed and AbdelAl, Omar and Shokrollahi, Siamak and Pitoc, Cloyd M and Aiello, Lloyd Paul and Silva, Paolo S}
}
@article {1154911,
	title = {Characterization of lincRNA expression in the human retinal pigment epithelium and differentiated induced pluripotent stem cells},
	journal = {PLoS One},
	volume = {12},
	number = {8},
	year = {2017},
	month = {2017},
	pages = {e0183939},
	abstract = {Long intervening non-coding RNAs (lincRNAs) are increasingly being implicated as important factors in many aspects of cellular development, function, and disease, but remain poorly understood. In this study, we examine the human retinal pigment epithelium (RPE) lincRNA transcriptome using RNA-Seq data generated from human fetal RPE (fRPE), RPE derived from human induced pluripotent stem cells (iPS-RPE), and undifferentiated iPS (iPS). In addition, we determine the suitability of iPS-RPE, from a transcriptome standpoint, as a model for use in future studies of lincRNA structure and function. A comparison of gene and isoform expression across the whole transcriptome shows only minimal differences between all sample types, though fRPE and iPS-RPE show higher concordance than either shows with iPS. Notably, RPE signature genes show the highest degree of fRPE to iPS-RPE concordance, indicating that iPS-RPE cells provide a suitable model for use in future studies. An analysis of lincRNAs demonstrates high concordance between fRPE and iPS-RPE, but low concordance between either RPE and iPS. While most lincRNAs are expressed at low levels (RPKM \&lt; 10), there is a high degree of concordance among replicates within each sample type, suggesting the expression is consistent, even at levels subject to high variability. Finally, we identified and annotated 180 putative novel genes in the fRPE samples, a majority of which are also expressed in the iPS-RPE. Overall, this study represents the first characterization of lincRNA expression in the human RPE, and provides a model for studying the role lincRNAs play in RPE development, function, and disease.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0183939},
	author = {Au, Elizabeth D and Fernandez-Godino, Rosario and Kaczynksi, Tadeusz J and Sousa, Maria E and Farkas, Michael H}
}
@article {1078711,
	title = {Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci},
	journal = {Nat Genet},
	year = {2017},
	month = {2017 May 29},
	abstract = {Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 {\texttimes} 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P \&lt; 5 {\texttimes} 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.},
	issn = {1546-1718},
	doi = {10.1038/ng.3875},
	author = {Aung, Tin and Ozaki, Mineo and Lee, Mei Chin and Schl{\"o}tzer-Schrehardt, Ursula and Thorleifsson, Gudmar and Mizoguchi, Takanori and Igo, Robert P and Haripriya, Aravind and Williams, Susan E and Astakhov, Yury S and Orr, Andrew C and Burdon, Kathryn P and Nakano, Satoko and Mori, Kazuhiko and Abu-Amero, Khaled and Hauser, Michael and Li, Zheng and Prakadeeswari, Gopalakrishnan and Bailey, Jessica N Cooke and Cherecheanu, Alina Popa and Kang, Jae H and Nelson, Sarah and Hayashi, Ken and Manabe, Shin-Ichi and Kazama, Shigeyasu and Zarnowski, Tomasz and Inoue, Kenji and Irkec, Murat and Coca-Prados, Miguel and Sugiyama, Kazuhisa and J{\"a}rvel{\"a}, Irma and Schlottmann, Patricio and Lerner, S Fabian and Lamari, Hasnaa and Nilg{\"u}n, Yildirim and Bikbov, Mukharram and Park, Ki Ho and Cha, Soon Cheol and Yamashiro, Kenji and Zenteno, Juan C and Jonas, Jost B and Kumar, Rajesh S and Perera, Shamira A and Chan, Anita S Y and Kobakhidze, Nino and George, Ronnie and Vijaya, Lingam and Do, Tan and Edward, Deepak P and de Juan Marcos, Lourdes and Pakravan, Mohammad and Moghimi, Sasan and Ideta, Ryuichi and Bach-Holm, Daniella and Kappelgaard, Per and Wirostko, Barbara and Thomas, Samuel and Gaston, Daniel and Bedard, Karen and Greer, Wenda L and Yang, Zhenglin and Chen, Xueyi and Huang, Lulin and Sang, Jinghong and Jia, Hongyan and Jia, Liyun and Qiao, Chunyan and Zhang, Hui and Liu, Xuyang and Zhao, Bowen and Wang, Ya-Xing and Xu, Liang and Leruez, St{\'e}phanie and Reynier, Pascal and Chichua, George and Tabagari, Sergo and Uebe, Steffen and Zenkel, Matthias and Berner, Daniel and Mossb{\"o}ck, Georg and Weisschuh, Nicole and Hoja, Ursula and Welge-Luessen, Ulrich-Christoph and Mardin, Christian and Founti, Panayiota and Chatzikyriakidou, Anthi and Pappas, Theofanis and Anastasopoulos, Eleftherios and Lambropoulos, Alexandros and Ghosh, Arkasubhra and Shetty, Rohit and Porporato, Natalia and Saravanan, Vijayan and Venkatesh, Rengaraj and Shivkumar, Chandrashekaran and Kalpana, Narendran and Sarangapani, Sripriya and Kanavi, Mozhgan R and Beni, Afsaneh Naderi and Yazdani, Shahin and Lashay, Alireza and Naderifar, Homa and Khatibi, Nassim and Fea, Antonio and Lavia, Carlo and Dallorto, Laura and Rolle, Teresa and Frezzotti, Paolo and Paoli, Daniela and Salvi, Erika and Manunta, Paolo and Mori, Yosai and Miyata, Kazunori and Higashide, Tomomi and Chihara, Etsuo and Ishiko, Satoshi and Yoshida, Akitoshi and Yanagi, Masahide and Kiuchi, Yoshiaki and Ohashi, Tsutomu and Sakurai, Toshiya and Sugimoto, Takako and Chuman, Hideki and Aihara, Makoto and Inatani, Masaru and Miyake, Masahiro and Gotoh, Norimoto and Matsuda, Fumihiko and Yoshimura, Nagahisa and Ikeda, Yoko and Ueno, Morio and Sotozono, Chie and Jeoung, Jin Wook and Sagong, Min and Park, Kyu Hyung and Ahn, Jeeyun and Cruz-Aguilar, Marisa and Ezzouhairi, Sidi M and Rafei, Abderrahman and Chong, Yaan Fun and Ng, Xiao Yu and Goh, Shuang Ru and Chen, Yueming and Yong, Victor H K and Khan, Muhammad Imran and Olawoye, Olusola O and Ashaye, Adeyinka O and Ugbede, Idakwo and Onakoya, Adeola and Kizor-Akaraiwe, Nkiru and Teekhasaenee, Chaiwat and Suwan, Yanin and Supakontanasan, Wasu and Okeke, Suhanya and Uche, Nkechi J and Asimadu, Ifeoma and Ayub, Humaira and Akhtar, Farah and Kosior-Jarecka, Ewa and Lukasik, Urszula and Lischinsky, Ignacio and Castro, Vania and Grossmann, Rodolfo Perez and Megevand, Gordana Sunaric and Roy, Sylvain and Dervan, Edward and Silke, Eoin and Rao, Aparna and Sahay, Priti and Fornero, Pablo and Cuello, Osvaldo and Sivori, Delia and Zompa, Tamara and Mills, Richard A and Souzeau, Emmanuelle and Mitchell, Paul and Wang, Jie Jin and Hewitt, Alex W and Coote, Michael and Crowston, Jonathan G and Astakhov, Sergei Y and Akopov, Eugeny L and Emelyanov, Anton and Vysochinskaya, Vera and Kazakbaeva, Gyulli and Fayzrakhmanov, Rinat and Al-Obeidan, Saleh A and Owaidhah, Ohoud and Aljasim, Leyla Ali and Chowbay, Balram and Foo, Jia Nee and Soh, Raphael Q and Sim, Kar Seng and Xie, Zhicheng and Cheong, Augustine W O and Mok, Shi Qi and Soo, Hui Meng and Chen, Xiao Yin and Peh, Su Qin and Heng, Khai Koon and Husain, Rahat and Ho, Su-Ling and Hillmer, Axel M and Cheng, Ching-Yu and Escudero-Dom{\'\i}nguez, Francisco A and Gonz{\'a}lez-Sarmiento, Rogelio and Martinon-Torres, Frederico and Salas, Antonio and Pathanapitoon, Kessara and Hansapinyo, Linda and Wanichwecharugruang, Boonsong and Kitnarong, Naris and Sakuntabhai, Anavaj and Nguyn, Hip X and Nguyn, Giang T T and Nguyn, Tr{\`\i}nh V and Zenz, Werner and Binder, Alexander and Klobassa, Daniela S and Hibberd, Martin L and Davila, Sonia and Herms, Stefan and N{\"o}then, Markus M and Moebus, Susanne and Rautenbach, Robyn M and Ziskind, Ari and Carmichael, Trevor R and Ramsay, Michele and {\'A}lvarez, Lydia and Garc{\'\i}a, Montserrat and Gonz{\'a}lez-Iglesias, H{\'e}ctor and Rodr{\'\i}guez-Calvo, Pedro P and Cueto, Luis Fern{\'a}ndez-Vega and Oguz, {\c C}ilingir and Tamcelik, Nevbahar and Atalay, Eray and Batu, Bilge and Aktas, Dilek and Kas{\i}m, Burcu and Wilson, M Roy and Coleman, Anne L and Liu, Yutao and Challa, Pratap and Herndon, Leon and Kuchtey, Rachel W and Kuchtey, John and Curtin, Karen and Chaya, Craig J and Crandall, Alan and Zangwill, Linda M and Wong, Tien Yin and Nakano, Masakazu and Kinoshita, Shigeru and den Hollander, Anneke I and Vesti, Eija and Fingert, John H and Lee, Richard K and Sit, Arthur J and Shingleton, Bradford J and Wang, Ningli and Cusi, Daniele and Qamar, Raheel and Kraft, Peter and Pericak-Vance, Margaret A and Raychaudhuri, Soumya and Heegaard, Steffen and Kivel{\"a}, Tero and Reis, Andr{\'e} and Kruse, Friedrich E and Weinreb, Robert N and Pasquale, Louis R and Haines, Jonathan L and Thorsteinsdottir, Unnur and Jonasson, Fridbert and Allingham, R Rand and Milea, Dan and Ritch, Robert and Kubota, Toshiaki and Tashiro, Kei and Vithana, Eranga N and Micheal, Shazia and Topouzis, Fotis and Craig, Jamie E and Dubina, Michael and Sundaresan, Periasamy and Stefansson, Kari and Wiggs, Janey L and Pasutto, Francesca and Khor, Chiea Chuen}
}
@article {382391,
	title = {A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.},
	journal = {Nat Genet},
	volume = {47},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {387-92},
	abstract = {Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 {\texttimes} 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: ORA allele = 9.87, P = 2.13 {\texttimes} 10(-217); non-Japanese: ORA allele = 0.49, P = 2.35 {\texttimes} 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.},
	issn = {1546-1718},
	doi = {10.1038/ng.3226},
	author = {Aung, Tin and Ozaki, Mineo and Mizoguchi, Takanori and Allingham, R Rand and Li, Zheng and Haripriya, Aravind and Nakano, Satoko and Uebe, Steffen and Harder, Jeffrey M and Chan, Anita S Y and Lee, Mei Chin and Burdon, Kathryn P and Astakhov, Yury S and Abu-Amero, Khaled K and Zenteno, Juan C and Nilg{\"u}n, Yildirim and Zarnowski, Tomasz and Pakravan, Mohammad and Safieh, Leen Abu and Jia, Liyun and Wang, Ya Xing and Williams, Susan and Paoli, Daniela and Schlottmann, Patricio G and Huang, Lulin and Sim, Kar Seng and Foo, Jia Nee and Nakano, Masakazu and Ikeda, Yoko and Kumar, Rajesh S and Ueno, Morio and Manabe, Shin-Ichi and Hayashi, Ken and Kazama, Shigeyasu and Ideta, Ryuichi and Mori, Yosai and Miyata, Kazunori and Sugiyama, Kazuhisa and Higashide, Tomomi and Chihara, Etsuo and Inoue, Kenji and Ishiko, Satoshi and Yoshida, Akitoshi and Yanagi, Masahide and Kiuchi, Yoshiaki and Aihara, Makoto and Ohashi, Tsutomu and Sakurai, Toshiya and Sugimoto, Takako and Chuman, Hideki and Matsuda, Fumihiko and Yamashiro, Kenji and Gotoh, Norimoto and Miyake, Masahiro and Astakhov, Sergei Y and Osman, Essam A and Al-Obeidan, Saleh A and Owaidhah, Ohoud and Al-Jasim, Leyla and Shahwan, Sami Al and Fogarty, Rhys A and Leo, Paul and Yetkin, Yaz and O{\u g}uz, {\c C}ilingir and Kanavi, Mozhgan Rezaei and Beni, Afsaneh Nederi and Yazdani, Shahin and Akopov, Evgeny L and Toh, Kai-Yee and Howell, Gareth R and Orr, Andrew C and Goh, Yufen and Meah, Wee Yang and Peh, Su Qin and Kosior-Jarecka, Ewa and Lukasik, Urszula and Krumbiegel, Mandy and Vithana, Eranga N and Wong, Tien Yin and Liu, Yutao and Koch, Allison E Ashley and Challa, Pratap and Rautenbach, Robyn M and Mackey, David A and Hewitt, Alex W and Mitchell, Paul and Wang, Jie Jin and Ziskind, Ari and Carmichael, Trevor and Ramakrishnan, Rangappa and Narendran, Kalpana and Venkatesh, Rangaraj and Vijayan, Saravanan and Zhao, Peiquan and Chen, Xueyi and Guadarrama-Vallejo, Dalia and Cheng, Ching Yu and Perera, Shamira A and Husain, Rahat and Ho, Su-Ling and Welge-Luessen, Ulrich-Christoph and Mardin, Christian and Schloetzer-Schrehardt, Ursula and Hillmer, Axel M and Herms, Stefan and Moebus, Susanne and N{\"o}then, Markus M and Weisschuh, Nicole and Shetty, Rohit and Ghosh, Arkasubhra and Teo, Yik Ying and Brown, Matthew A and Lischinsky, Ignacio and Blue Mountains Eye Study GWAS Team and Wellcome Trust Case Control Consortium 2 and Crowston, Jonathan G and Coote, Michael and Zhao, Bowen and Sang, Jinghong and Zhang, Nihong and You, Qisheng and Vysochinskaya, Vera and Founti, Panayiota and Chatzikyriakidou, Anthoula and Lambropoulos, Alexandros and Anastasopoulos, Eleftherios and Coleman, Anne L and Wilson, M Roy and Rhee, Douglas J and Kang, Jae Hee and May-Bolchakova, Inna and Heegaard, Steffen and Mori, Kazuhiko and Alward, Wallace L M and Jonas, Jost B and Xu, Liang and Liebmann, Jeffrey M and Chowbay, Balram and Schaeffeler, Elke and Schwab, Matthias and Lerner, Fabian and Wang, Ningli and Yang, Zhenglin and Frezzotti, Paolo and Kinoshita, Shigeru and Fingert, John H and Inatani, Masaru and Tashiro, Kei and Reis, Andr{\'e} and Edward, Deepak P and Pasquale, Louis R and Kubota, Toshiaki and Wiggs, Janey L and Pasutto, Francesca and Topouzis, Fotis and Dubina, Michael and Craig, Jamie E and Yoshimura, Nagahisa and Sundaresan, Periasamy and John, Simon W M and Ritch, Robert and Hauser, Michael A and Khor, Chiea-Chuen}
}
@article {959376,
	title = {The Targetable Epigenetic Tumor Protein EZH2 is Enriched in Intraocular Medulloepithelioma.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {14},
	year = {2016},
	month = {2016 Nov 01},
	pages = {6242-6246},
	abstract = {Purpose: Intraocular medulloepithelioma (IM), the second most common primary neuroepithelial tumor of the eye, can lead to blindness in the affected eye and in rare cases, is deadly. Intraocular medulloepithelioma lacks targetable biomarkers for potential pharmacologic therapy. The purpose of this study was to identify actionable, tumor-specific proteins for potential diagnostic or therapeutic strategies. We hypothesize that the tumor-specific epigenetic enzyme EZH2 is selectively expressed in IM. Methods: We conducted a retrospective case series study of five IM from five eyes of four children and one adult. Hematoxylin and eosin (H\&amp;E) stains of sections from formalin-fixed, paraffin-embedded blocks of IM tumors were used to localize IM tumor cells in each case. Using an EZH2-specific antibody for immunohistochemistry, we semiquantitatively calculated the proportion of IM tumor cells positive for EZH2, and also assayed for EZH2 staining intensity. Results: We found that EZH2 was expressed in all IM cases but this protein was absent in nontumor ciliary body or retinal tissues. However, not all IM tumor cells expressed EZH2. Similar to retinoblastoma, moderately to poorly differentiated (primitive appearing) IM tumor cells strongly expressed EZH2; expression was weaker or absent in areas of well-formed neuroepithelial units. Conclusions: To our knowledge, this is the first study to identify an actionable tumor-specific maker, EZH2, in IM. Our findings point to the possibility of exploring the potential of EZH2 inhibitors, already in clinical trials for other cancers, for IM.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20463},
	author = {Avedschmidt, Sarah E and Stagner, Anna M and Eagle, Ralph C and Harocopos, George J and Dou, Yali and Rao, Rajesh C}
}
@article {959381,
	title = {Orbital/Periorbital Plexiform Neurofibromas in Children with Neurofibromatosis Type 1: Multidisciplinary Recommendations for Care.},
	journal = {Ophthalmology},
	volume = {124},
	number = {1},
	year = {2017},
	month = {2017 Jan},
	pages = {123-132},
	abstract = {TOPIC: Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. CLINICAL RELEVANCE: Although NF1 is a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. Although medical and surgical interventions have been reported, there are no agreed-on criteria for when OPPNs require therapy and which treatment produces the best outcome. METHODS: Because a multidisciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics, and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual or aesthetic sequelae complicates the design of evidence-based studies and feasible clinical trials. RESULTS: In September 2013, a multidisciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. CONCLUSIONS: This consensus statement provides recommendations for ophthalmologic monitoring, outlines treatment indications and forthcoming biologic therapy, and discusses challenges to performing clinical trials in this complicated condition.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.09.020},
	author = {Avery, Robert A and Katowitz, James A and Fisher, Michael J and Heidary, Gena and Dombi, Eva and Packer, Roger J and Widemann, Brigitte C and OPPN Working Group}
}
@article {1782396,
	title = {High temporal frequency light response in mouse retina is mediated by ON and OFF bipolar cells and requires FAT3 signaling},
	journal = {bioRxiv},
	year = {2023},
	month = {2023 Nov 04},
	abstract = {Vision is initiated by the reception of light by photoreceptors and subsequent processing via parallel retinal circuits. Proper circuit organization depends on the multi-functional tissue polarity protein FAT3, which is required for amacrine cell connectivity and retinal lamination. Here we investigated the retinal function of Fat3 mutant mice and found decreases in physiological and perceptual responses to high frequency flashes. These defects did not correlate with abnormal amacrine cell wiring, pointing instead to a role in bipolar cell subtypes that also express FAT3. Indeed, similar deficits were observed in mice lacking the bipolar cell glutamate receptors GRIK1 (OFF-bipolar cells) and GRM6 (ON-bipolar cells). Mechanistically, FAT3 binds to the synaptic protein PTPσ and is required to localize GRIK1 to OFF-cone bipolar cell synapses with cone photoreceptors. How FAT3 impacts ON-cone bipolar cell function at high temporal frequency remains to be uncovered. These findings expand the repertoire of FAT3{\textquoteright}s functions and reveal the importance of both ON- and OFF-bipolar cells for high frequency light response.},
	doi = {10.1101/2023.11.02.565326},
	author = {Avil{\'e}s, Evelyn C and Wang, Sean K and Patel, Sarina and Shi, Shuxiang and Lin, Lucas and Kefalov, Vladimir J and Goodrich, Lisa V and Cepko, Constance L and Xue, Yunlu}
}
@article {1608593,
	title = {Retinal prosthetic vision simulation: temporal aspects},
	journal = {J Neural Eng},
	volume = {18},
	number = {4},
	year = {2021},
	month = {2021 Aug 24},
	abstract = {Objective. The perception of individuals fitted with retinal prostheses is not fully understood, although several retinal implants have been tested and commercialized. Realistic simulations of perception with retinal implants would be useful for future development and evaluation of such systems.Approach.We implemented a retinal prosthetic vision simulation, including temporal features, which have not been previously simulated. In particular, the simulation included temporal aspects such as persistence and perceptual fading of phosphenes and the electrode activation rate.Main results.The simulated phosphene persistence showed an effective reduction in flickering at low electrode activation rates. Although persistence has a positive effect on static scenes, it smears dynamic scenes. Perceptual fading following continuous stimulation affects prosthetic vision of both static and dynamic scenes by making them disappear completely or partially. However, we showed that perceptual fading of a static stimulus might be countered by head-scanning motions, which together with the persistence revealed the contours of the faded object. We also showed that changing the image polarity may improve simulated prosthetic vision in the presence of persistence and perceptual fading.Significance.Temporal aspects have important roles in prosthetic vision, as illustrated by the simulations. Considering these aspects may improve the future design, the training with, and evaluation of retinal prostheses.},
	issn = {1741-2552},
	doi = {10.1088/1741-2552/ac1b6c},
	author = {Avraham, David and Jung, Jae-Hyun and Yitzhaky, Yitzhak and Peli, Eli}
}
@article {284011,
	title = {Author reply: To PMID 23972322},
	journal = {Ophthalmology},
	volume = {121},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {e39},
	keywords = {Antioxidants, Female, Humans, Macular Degeneration, Male, Polymorphism, Single Nucleotide, Proteins, Zinc Compounds},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.02.029},
	author = {Awh, Carl C and Lane, Anne Marie and Hawken, Steven and Zanke, Brent and Kim, Ivana K}
}
@article {1814406,
	title = {Characteristics of Eyes With CRB1-Associated EOSRD/LCA: Age-Related Changes},
	journal = {Am J Ophthalmol},
	volume = {263},
	year = {2024},
	month = {2024 Mar 10},
	pages = {168-178},
	abstract = {PURPOSE: To evaluate ocular and retinal features of CRB1-associated early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) for age-related changes. DESIGN: Retrospective cohort study. METHODS: Sixteen pediatric patients with biallelic CRB1 EOSRD/LCA who had been followed for up to 18 years were reviewed. Results of comprehensive ophthalmic examinations-including visual acuity, refractive error, dark-adapted visual threshold, Goldmann perimetry, and macular optical coherence tomography (OCT)-were analyzed for significant age-related changes using mixed-effects models. RESULTS: Visual acuity dark-adapted visual sensitivity, and area of seeing visual field (all subnormal from the earliest ages recorded) declined with increasing age. Hyperopia was stable through childhood and adolescence. In CRB1 EOSRD/LCA, OCT extrafoveal inner and outer laminar thicknesses exceeded those in controls but varied little with age, and foveal metrics (depth, breadth, thickness at rim) differed significantly from those in controls, but variations in foveal metrics were not associated with declines in acuity. CONCLUSIONS: From the youngest ages, retinal and visual function is significantly subnormal and becomes progressively compromized. A goal of future therapies should be intervention at young ages, when there is more function to be rescued.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2024.02.028},
	author = {Ayash, Jad and Woods, Russell L and Akula, James D and Rajabi, Farrah and AlWattar, Bilal K and Altschwager, Pablo and Fulton, Anne B}
}
@article {1538344,
	title = {Trends in Anti-Vascular Endothelial Growth Factor Agents and Panretinal Photocoagulation Use in Diabetic Retinopathy},
	journal = {Ophthalmol Retina},
	volume = {5},
	number = {4},
	year = {2021},
	month = {2021 04},
	pages = {390-392},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2020.10.002},
	author = {Azad, Amee D and Chen, Evan M and Hinkle, John and Rayess, Nadim and Wu, David and Eliott, Dean and Mruthyunjaya, Prithvi and Parikh, Ravi}
}
@article {1806611,
	title = {Slate Grey Eyelid Pigmentation in a Patient With Hemochromatosis and Prior Hydroxychloroquine Use},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2024},
	month = {2024 Feb 02},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002609},
	author = {Azad, Amee D and Chiou, Carolina A and Stagner, Anna M and Freitag, Suzanne K}
}
@article {1522719,
	title = {Anti-Vascular Endothelial Growth Factor and Panretinal Photocoagulation Use after Protocol S for Proliferative Diabetic Retinopathy},
	journal = {Ophthalmol Retina},
	volume = {5},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {151-159},
	abstract = {PURPOSE: To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the Diabetic Retinopathy Clinical Research Network protocol S. DESIGN: A retrospective, cross-sectional study from January 2012, through September 2019, using a nationally representative claims-based database, Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). PARTICIPANTS: Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF agents. METHODS: Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 2015). MAIN OUTCOME MEASURES: Annual rates of anti-VEGF or PRP treatments per 1000 treated eyes with PDR. RESULTS: From 2012 through 2019, 10 035 PRP or anti-VEGF treatments were administered to 3685 PDR eyes. Of these, 63.6\% (n\&nbsp;= 6379) were anti-VEGF agents, and 36.4\% (n\&nbsp;= 3656) were PRP treatments. Throughout treatment, 88.7\% of eyes treated with anti-VEGF received the same agent and 7.7\% were treated with both PRP and anti-VEGF agents. Panretinal photocoagulation rates declined from 784/1000 treated eyes in 2012 to 566/1000 in 2019 (pre-Protocol S: β\&nbsp;= -32 vs. post-Protocol S: -77; P\&nbsp;= 0.005), whereas anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (β\&nbsp;= -48 vs. 161, respectively; P\&nbsp;= 0.001). Panretinal photocoagulation rates in diabetic macular edema (DME) eyes did not significantly differ from 474/1000 in 2012 to 363/1000 in 2019 (β\&nbsp;= -9 vs. -58 respectively; P\&nbsp;= 0.091), and anti-VEGF rates increased from 1533/1000 in 2012 to 2096/1000 in 2019 (β\&nbsp;= -57 vs. 187; P\&nbsp;= 0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (β\&nbsp;= -31 vs. -111, respectively; P \&lt; 0.001), and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (β\&nbsp;= -48 vs. 140, respectively; P \&lt; 0.001). CONCLUSIONS: Following the publication of Protocol S, PRP rates decreased, while anti-VEGF rates increased. Panretinal photocoagulation rates did not significantly change among eyes with DME. Our findings indicate the impact that randomized controlled trials can have on real-world practice patterns.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2020.07.018},
	author = {Azad, Amee D and Chen, Evan M and Hinkle, John and Rayess, Nadim and Wu, David and Eliott, Dean and Mruthyunjaya, Prithvi and Parikh, Ravi}
}
@article {1732651,
	title = {Hyperglobus and Pseudoptosis in Type 1 Lipogenic Thyroid Eye Disease},
	journal = {Am J Ophthalmol Case Rep},
	volume = {32},
	year = {2023},
	month = {2023 Dec},
	pages = {101890},
	abstract = {PURPOSE: We present a case of Type 1 (lipogenic) Thyroid Eye Disease (TED) and our aim is to describe an atypical presentation of a rare orbital process. OBSERVATIONS: A man in his 50s presented with left-sided eyelid drooping. His exam showed no evidence of active inflammation but did show left hyperglobus and ipsilateral upper eyelid pseudoptosis. He had no prior history or symptoms of Graves{\textquoteright} Disease and imaging did not show evidence of extraocular muscle enlargement, bony asymmetries, or masses in the orbit. Subsequent lab work showed a low TSH (thyroid-stimulating hormone), elevated free T4 (thyroxine) and T3 (triiodothyronine), and elevated TSI (thyroid-stimulating immunoglobulin) index. CONCLUSIONS AND IMPORTANCE: This is a unique and atypical presentation of a patient diagnosed with Type 1 (lipogenic) TED causing hyperglobus and pseudoptosis secondary to fat expansion in the absence of other classic TED findings such as contralateral eyelid retraction or extraocular muscle enlargement. Thyroid eye disease can have a heterogenous disease presentation, as evidenced by this case, and should always be considered in the differential diagnosis of pseudoptosis.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2023.101890},
	author = {Azad, Amee D and Reshef, Edith R and Lee, Nahyoung Grace}
}
@article {1626090,
	title = {Representation of Women in Ophthalmology Subspecialty Societies over 20 Years},
	journal = {Ophthalmology},
	volume = {129},
	number = {5},
	year = {2022},
	month = {2022 05},
	pages = {587-590},
	keywords = {Female, Humans, Ophthalmology, Societies, Medical},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.12.011},
	author = {Azad, Amee D and Chandramohan, Arthika and Li, Angela S and Rosenblatt, Tatiana R and Reeves, Mary-Grace R and Veerappan-Pasricha, Malini and Ludwig, Cassie A and Nguyen, Angeline and Winges, Kimberly M and Wang, Sophia Y and Pan, Carolyn K and Moss, Heather E and Do, Diana V and Fountain, Tamara R and Kossler, Andrea L}
}
@article {1761851,
	title = {The Transition to Ophthalmology Residency: A National Survey of the Combined Ophthalmology PGY-1 Program},
	journal = {J Acad Ophthalmol (2017)},
	volume = {15},
	number = {2},
	year = {2023},
	month = {2023 Jul},
	pages = {e188-e196},
	abstract = {Background   In 2017, the Accreditation Council for Graduate Medical Education announced all ophthalmology residency programs would provide a combined transitional or joint preliminary program for first postgraduate year (PGY-1) residents, with mandatory implementation by 2023. Purpose   This study aimed to survey ophthalmology residency program directors, postgraduate year 2 (PGY-2) ophthalmology residents who were a part of the first, official combined ophthalmology PGY-1 year, and postgraduate year 3 (PGY-3) residents who were a PGY-1 resident the year prior to integration to evaluate characteristics and perspectives on the combined ophthalmology PGY-1 year. Methods   A national, internet survey-based study approved by the Association of University Professors of Ophthalmology (AUPO) was disseminated to the AUPO listserv of program directors (PDs) and PGY-2 and PGY-3 ophthalmology residents from July to August 2022 and then again April to June 2023. Results   Twenty-six PDs completed the survey (response rate 20.3\% out of 128 PDs). Forty-one PGY-2 ophthalmology residents who underwent the combined ophthalmology PGY-1 year and 33 PGY-3 ophthalmology residents also completed the survey. Most PGY-1 curricula focused on exposure to comprehensive ophthalmology and provided indirect ophthalmoscope, slit lamp, and refraction skills training to residents. Early exposure to fundamentals and clinical workflows were commonly cited benefits to the integration. When PDs were surveyed about how well-prepared PGY-1 residents who went through the combined year are for the PGY-2 relative to the prior year{\textquoteright}s class, 16 (61.5\%) responded "better prepared." PGY-2 residents also reported a relatively higher level of clinical preparedness and familiarity with ophthalmology co-residents than PGY-3 residents. Several areas of improvement cited by both PDs and residents were identified including a dedicated didactic curriculum and more time in ophthalmology during the PGY-1 year. Conclusions   We found an overall net benefit from the integration of the combined ophthalmology PGY-1 year. Benefits include early exposure to clinical skills and knowledge specific to ophthalmology, leading to increased confidence and preparedness for the rigorous transition to ophthalmology residency. We also identified many areas for improvement to optimize the PGY-1 year including a formal curriculum and additional time in ophthalmology. Programs should work closely with their residents, faculty, and non-ophthalmology PDs to refine the PGY-1 for the benefit of future ophthalmologists.},
	issn = {2475-4757},
	doi = {10.1055/s-0043-1774393},
	author = {Azad, Amee D and Yuan, Melissa and Weinert, Marguerite and Rosenblatt, Tatiana R and Miller, Joan W and Lorch, Alice}
}
@article {1615215,
	title = {Association of Patient Characteristics With Delivery of Ophthalmic Telemedicine During the COVID-19 Pandemic},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {11},
	year = {2021},
	month = {2021 11 01},
	pages = {1174-1182},
	abstract = {Importance: Telemedicine has been shown to have had reduced uptake among historically marginalized populations within multiple medical specialties during the COVID-19 pandemic. An evaluation of health disparities among patients receiving ophthalmic telemedical care during the pandemic is needed. Objective: To evaluate disparities in the delivery of ophthalmic telemedicine at Massachusetts Eye and Ear (MEE) during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective, cross-sectional study analyzed clinical visits at a single tertiary eye care center (MEE) from January 1 to December 31, 2020. Patients who had ophthalmology and optometry clinical visits at the MEE during the study period were included. Exposures: Telemedicine vs in-person clinical encounters. Main Outcomes and Measures: Variables associated with use of ophthalmic telemedicine during the study period. Results: A total of 2262 telemedicine ophthalmic encounters for 1911 patients were included in the analysis. The median age of the patients was 61 (interquartile range, 43-72) years, and 1179 (61.70\%) were women. With regard to race and ethnicity, 87 patients (4.55\%) identified as Asian; 128 (6.70\%), as Black or African American; 23 (1.20\%), as Hispanic or Latino; and 1455 (76.14\%), as White. On multivariate analysis, factors associated with decreased receipt of telemedical care included male sex (odds ratio [OR], 0.86; 95\% CI, 0.77-0.96), Black race (OR, 0.69; 95\% CI, 0.56-0.86), not speaking English (OR, 0.63; 95\% CI, 0.48-0.81), educational level of high school or less (OR, 0.83; 95\% CI, 0.71-0.97), and age (OR per year of age, 0.99; 95\% CI, 0.989-0.998). When comparing telephone- and video-based telemedicine visits, decreased participation in video-based visits was associated with age (OR per year of age, 0.96; 95\% CI, 0.94-0.98), educational level of high school or less (OR, 0.54; 95\% CI, 0.29-0.99), being unemployed (OR, 0.28; 95\% CI, 0.12-0.68), being retired (OR, 0.22; 95\% CI, 0.10-0.42), or having a disability (OR, 0.09; 95\% CI, 0.04-0.23). Conclusions and Relevance: The findings of this cross-sectional study, though limited to retrospective data from a single university-based practice, suggest that historically marginalized populations were less likely to receive ophthalmic telemedical care compared with in-person care during the first year of the COVID-19 pandemic in the US. Understanding the causes of these disparities might help those who need access to virtual care.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.3728},
	author = {Aziz, Kanza and Moon, Jade Y and Parikh, Ravi and Lorch, Alice C and Friedman, David S and Miller, John B and Armstrong, Grayson W}
}
@article {1347424,
	title = {Clinical Features of a Retinopathy Associated With a Dominant Allele of the RGR Gene},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {12},
	year = {2018},
	month = {2018 Oct 01},
	pages = {4812-4820},
	abstract = {Purpose: We describe the clinical features in two pedigrees with dominantly inherited retinopathy segregating the previously reported frameshifting mutation, c.836dupG (p.Ile280Asn*78) in the terminal exon of the RGR gene, and compare their haplotypes to that of the previously reported pedigree. Methods: The probands were ascertained at West Virginia University Eye Institute (WVU) and Moorfields Eye Hospital (MEH) through next generation sequencing (NGS) and whole genome sequencing (WGS) respectively. Clinical data included visual acuity (VA), visual fields, fundus autofluorescence (FAF), optical coherence tomography (OCT), and electroretinography (ERG). Haplotype analysis was performed using Sanger sequencing of the DNA from the molecularly ascertained individuals from the three pedigrees. Results: Nine heterozygous mutation carriers were identified in two families. Four carriers were asymptomatic; five carriers had variable VA reduction, visual field constriction, and experienced difficulty under dim illumination. Fundus examination of the asymptomatic carriers showed diffuse or reticular pigmentation of the retina; the symptomatic carriers had chorioretinal atrophy. FAF imaging showed widespread signal loss in advanced retinopathy, and reticular hyperautofluorescence in mild cases. OCT showed loss of outer retinal lamina in advanced disease. ERG showed moderate-to-severe rod-cone dysfunction in two symptomatic carriers; and was normal in three asymptomatic carriers. A shared haplotype flanking the mutation of up to 6.67 Mb was identified in both families. Within this region, 1.27 Mb were shared with the first family reported with this retinopathy. Conclusions: The clinical data suggest a variable and slow degeneration of the RPE. A shared chromosomal segment surrounding the RGR gene suggests a single ancestral mutational event underlying all three families.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-25061},
	author = {Ba-Abbad, Rola and Leys, Monique and Wang, Xinjing and Chakarova, Christina and Waseem, Naushin and Carss, Keren J and Raymond, F Lucy and Bujakowska, Kinga M and Pierce, Eric A and Mahroo, Omar A and Mohamed, Moin D and Holder, Graham E and Hummel, Marybeth and Arno, Gavin and Webster, Andrew R}
}
@article {1439844,
	title = {Microperimetry in Three Inherited Retinal Disorders},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 May 30},
	pages = {1-6},
	abstract = {Microperimetry (MP) is used to assess visual sensitivity mediated by the central retina. As such, MP performance is a candidate outcome measure for gene therapy trials. Herein, we review MP results in three inherited retinal disorders for which gene therapy trials have been initiated-choroideremia, Stargardt disease, and X-linked juvenile retinoschisis. Each of these disorders typically presents in childhood and each has distinct effects on the central retina. Our review indicates that microperimetry is feasible in each of these conditions. The MP sensitivity maps vary among conditions consistent with known effects of each of the three conditions. There is, however, within each of the three disorders considerable variability in fixation stability and in the pattern of sensitivity loss. Microperimetry is a valuable tool for monitoring functional aspects of central retina in an individual patient, especially in combination with other modalities such as OCT, autofluorescence, and acuity and thus may contribute to evaluating the efficacy of gene treatments. Variability of the MP parameters raises some cautions in application of MP as an outcome measure in treatment trials that may have small sample sizes. Nonetheless, we suspect that MP will continue to have a rightful place in future gene therapy trials.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1622025},
	author = {Bagdonaite-Bejarano, Laura and Hansen, Ronald M and Fulton, Anne B}
}
@article {1154916,
	title = {A NOVEL LARGE HOMOZYGOUS DELETION IN THE CELLULAR RETINALDEHYDE-BINDING PROTEIN GENE (RLBP1) IN A PATIENT WITH RETINITIS PUNCTATA ALBESCENS},
	journal = {Retin Cases Brief Rep},
	volume = {14},
	number = {1},
	year = {2020},
	month = {2020 Winter},
	pages = {85-89},
	abstract = {PURPOSE: To report the phenotypic and genotypic data of a patient with retinitis punctata albescens carrying a novel deletion in the RLBP1 gene. RESULTS: A woman of Iranian descent in her forties with a history of progressive visual deterioration since early childhood exhibited phenotypic features of retinitis punctata albescens with multiple white dots in the posterior pole and macular atrophy in both eyes. The microarray analysis identified a \~{}2.160 kb homozygous deletion corresponding to a minimum deletion boundary of chr15q26.1:89,756,882-89,759,041/GRCh37 (hg19), which encompasses exon 6 of the RLBP1 gene. CONCLUSION: We describe a novel large homozygous deletion in the RLBP1 gene encoding the cellular retinaldehyde-binding protein in a patient of Iranian descent with retinitis punctata albescens. Genotype-phenotype studies may provide more information about the functions of the RLBP1 encoding proteins and the disease course, because RLBP1 mutations are associated with high phenotypic variability and are therefore a necessity for future tailored individual therapies.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000628},
	author = {Bagheri, Saghar and Pantrangi, Madhulatha and Sodhi, Simrat K and Bagheri, Sayeh and Oellers, Patrick and Scholl, Hendrik P N}
}
@article {1532375,
	title = {Angiogenic responses in a 3D micro-engineered environment of primary endothelial cells and pericytes},
	journal = {Angiogenesis},
	year = {2020},
	month = {2020 Sep 21},
	abstract = {Angiogenesis plays a key role in the pathology of diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. Understanding the driving forces of endothelial cell migration and organization, as well as the time frame of these processes, can elucidate mechanisms of action of important pathological pathways. Herein, we have developed an organ-specific microfluidic platform recapitulating the in vivo angiogenic microenvironment by co-culturing mouse primary brain endothelial cells with brain pericytes in a three-dimensional (3D) collagen scaffold. As a proof of concept, we show that this model can be used for studying the angiogenic process and further comparing the angiogenic properties between two different common inbred mouse strains, C57BL/6J and 129S1/SvlmJ. We further show that the newly discovered angiogenesis-regulating gene Padi2 promotes angiogenesis through Dll4/Notch1 signaling by an on-chip mechanistic study. Analysis of the interplay between primary endothelial cells and pericytes in a 3D microfluidic environment assists in the elucidation of the angiogenic response.},
	issn = {1573-7209},
	doi = {10.1007/s10456-020-09746-6},
	author = {Bai, Jing and Khajavi, Mehrdad and Sui, Lufei and Fu, Haojie and Krishnaji, Subrahmanian Tarakkad and Birsner, Amy E and Bazinet, Lauren and Kamm, Roger D and D{\textquoteright}Amato, Robert J}
}
@article {1302191,
	title = {Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {2},
	year = {2018},
	month = {2018 Feb 01},
	pages = {629-636},
	abstract = {Purpose: Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods: We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results: In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P <= 0.033) and not women (permuted P >= 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P <= 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions: Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-22708},
	author = {Bailey, Jessica N Cooke and Gharahkhani, Puya and Kang, Jae H and Butkiewicz, Mariusz and Sullivan, David A and Weinreb, Robert N and Aschard, Hugues and Allingham, R Rand and Ashley-Koch, Allison and Lee, Richard K and Moroi, Sayoko E and Brilliant, Murray H and Wollstein, Gadi and Schuman, Joel S and Fingert, John H and Budenz, Donald L and Realini, Tony and Gaasterland, Terry and Scott, William K and Singh, Kuldev and Sit, Arthur J and Igo, Robert P and Song, Yeunjoo E and Hark, Lisa and Ritch, Robert and Rhee, Douglas J and Vollrath, Douglas and Zack, Donald J and Medeiros, Felipe and Vajaranant, Thasarat S and Chasman, Daniel I and Christen, William G and Pericak-Vance, Margaret A and Liu, Yutao and Kraft, Peter and Richards, Julia E and Rosner, Bernard A and Hauser, Michael A and Craig, Jamie E and Burdon, Kathryn P and Hewitt, Alex W and Mackey, David A and Haines, Jonathan L and Macgregor, Stuart and Wiggs, Janey L and Pasquale, Louis R and Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium}
}
@article {630221,
	title = {Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.},
	journal = {Nat Genet},
	volume = {48},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {189-94},
	abstract = {Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 {\texttimes} 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 {\texttimes} 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 {\texttimes} 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.},
	issn = {1546-1718},
	doi = {10.1038/ng.3482},
	author = {Bailey, Jessica N Cooke and Loomis, Stephanie J and Kang, Jae H and Allingham, R Rand and Gharahkhani, Puya and Khor, Chiea Chuen and Burdon, Kathryn P and Aschard, Hugues and Chasman, Daniel I and Igo, Robert P and Hysi, Pirro G and Glastonbury, Craig A and Ashley-Koch, Allison and Brilliant, Murray and Brown, Andrew A and Budenz, Donald L and Buil, Alfonso and Cheng, Ching-Yu and Choi, Hyon and Christen, William G and Curhan, Gary and De Vivo, Immaculata and Fingert, John H and Foster, Paul J and Fuchs, Charles and Gaasterland, Douglas and Gaasterland, Terry and Hewitt, Alex W and Hu, Frank and Hunter, David J and Khawaja, Anthony P and Lee, Richard K and Li, Zheng and Lichter, Paul R and Mackey, David A and McGuffin, Peter and Mitchell, Paul and Moroi, Sayoko E and Perera, Shamira A and Pepper, Keating W and Qi, Qibin and Realini, Tony and Richards, Julia E and Ridker, Paul M and Rimm, Eric and Ritch, Robert and Ritchie, Marylyn and Schuman, Joel S and Scott, William K and Singh, Kuldev and Sit, Arthur J and Song, Yeunjoo E and Tamimi, Rulla M and Topouzis, Fotis and Viswanathan, Ananth C and Verma, Shefali Setia and Vollrath, Douglas and Wang, Jie Jin and Weisschuh, Nicole and Wissinger, Bernd and Wollstein, Gadi and Wong, Tien Y and Yaspan, Brian L and Zack, Donald J and Zhang, Kang and Study, Epic-Norfolk Eye and ANZRAG Consortium and Weinreb, Robert N and Pericak-Vance, Margaret A and Small, Kerrin and Hammond, Christopher J and Aung, Tin and Liu, Yutao and Vithana, Eranga N and Macgregor, Stuart and Craig, Jamie E and Kraft, Peter and Howell, Gareth and Hauser, Michael A and Pasquale, Louis R and Haines, Jonathan L and Wiggs, Janey L}
}
@article {1282091,
	title = {Aqueous Drainage Device Erosion: A Review of Rates, Risks, Prevention, and Repair},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Dec 06},
	pages = {1-10},
	abstract = {Aqueous drainage device tube erosions require prompt intervention to prevent endophthalmitis. As the use of drainage devices in glaucoma surgery continues to increase, recognizing and managing tube erosions is a pertinent issue. This review provides a comprehensive overview of tube erosions, including the rates of erosion with various types of patch grafts, the risk factors associated with erosion, and approaches to repair in order to counsel and treat our patients to prevent endophthalmitis.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353805},
	author = {Bains, Upneet and Hoguet, Ambika}
}
@article {1478334,
	title = {Emerging Treatments for Leber{\textquoteright}s Hereditary Optic Neuropathy and Other Genetic Causes of Visual Loss},
	journal = {Semin Neurol},
	volume = {39},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {732-738},
	abstract = {Leber{\textquoteright}s hereditary optic neuropathy (LHON) and other genetic causes of visual loss are important clinical entities that can cause profound visual loss. To date, therapeutic options have been quite limited, but insights into the genetic basis of these diseases and advances in the ability to deliver effective and safe gene therapy have opened the door for new therapeutics that may revolutionize the approach to treating these conditions. This article reviews emerging gene therapies of LHON and other inherited ophthalmological diseases, addressing the technical, clinical, and ethical challenges that researchers and clinicians will encounter as new treatments become available for these conditions.},
	issn = {1098-9021},
	doi = {10.1055/s-0039-3399504},
	author = {Bakaeva, Tatiana and Mallery, Robert and Prasad, Sashank}
}
@article {1580505,
	title = {SARS-CoV-2 safety: Guidelines for shielding frontline nurses},
	journal = {Nursing},
	volume = {51},
	number = {3},
	year = {2021},
	month = {2021 Mar 01},
	pages = {32-42},
	abstract = {ABSTRACT: Protecting nurses in healthcare facilities from SARS-CoV-2 infection is essential for maintaining an adequate nursing force. Foundational guidelines, consistently utilized, protect the nursing staff from infection. This article describes guidelines designed to reduce acute infection and associated morbidity and mortality among nursing staff and improve compliance with infection prevention protocols.},
	keywords = {COVID-19, Hand Hygiene, Humans, Infection Control, Infectious Disease Transmission, Patient-to-Professional, Nursing Staff, Personal Protective Equipment, Practice Guidelines as Topic, Respiratory Protective Devices},
	issn = {1538-8689},
	doi = {10.1097/01.NURSE.0000733932.88107.44},
	author = {Baker, Terrance L and Greiner, Jack V and Vesonder, Modesta}
}
@article {1435393,
	title = {Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial},
	journal = {JAMA},
	year = {2019},
	month = {2019 Apr 29},
	abstract = {Importance: Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown. Objective: To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation. Design, Setting, and Participants: Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018. Interventions: Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (>= 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits. Main Outcomes and Measures: The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists{\textquoteright} Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported. Results: Among 702 randomized participants (mean age, 59 years; 38\% female [n=264]), 625 of 681 (92\% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25\% (60/240) and 34\% (80/326) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16\% (33/205), 17\% (36/212), and 19\% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2\% [95\% CI, -9\% to 5\%]; relative risk, 0.88 [95\% CI, 0.57-1.35; P = .79]; aflibercept vs observation risk difference, -3\% [95\% CI, -11\% to 4\%]; relative risk, 0.83 [95\% CI, 0.55-1.27; P = .79]; laser photocoagulation vs observation risk difference, -1\% [95\% CI, -9\% to 6\%]; relative risk, 0.95 [95\% CI, 0.64-1.41; P = .79]). Antiplatelet Trialists{\textquoteright} Collaboration vascular events occurred in 15 (7\%), 13 (5\%), and 8 (3\%) participants in the aflibercept, laser photocoagulation, and observation groups. Conclusions and Relevance: Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME. Trial Registration: ClinicalTrials.gov Identifier: NCT01909791.},
	issn = {1538-3598},
	doi = {10.1001/jama.2019.5790},
	author = {Baker, Carl W and Glassman, Adam R and Beaulieu, Wesley T and Antoszyk, Andrew N and Browning, David J and Chalam, Kakarla V and Grover, Sandeep and Jampol, Lee M and Jhaveri, Chirag D and Melia, Michele and Stockdale, Cynthia R and Martin, Daniel F and Sun, Jennifer K and DRCR Retina Network}
}
@article {1661615,
	title = {Comparison of Snellen Visual Acuity Measurements in Retinal Clinical Practice to Electronic ETDRS Protocol Visual Acuity Assessment},
	journal = {Ophthalmology},
	volume = {130},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {533-541},
	abstract = {PURPOSE: Evaluate the differences between clinical visual acuity (VA) as recorded in medical records and electronic Early Treatment Diabetic Retinopathy Study (eETDRS) protocol VA measurements and factors affecting the size of the differences. DESIGN: Retrospective chart review. PARTICIPANTS: Study and fellow eyes of participants enrolled in DRCR Retina Network Protocols AC and AE (diabetic macular edema), and W (nonproliferative diabetic retinopathy) with clinical VA recorded within 3 months before the protocol visit. METHODS: Differences and their association with patient and ocular factors were evaluated using linear mixed models with random effects for correlations within sites and participants. MAIN OUTCOME MEASURE: Difference between VA letter scores measured by eETDRS during a study visit versus measured by Snellen during a regular clinical visit (Snellen fraction converted to eETDRS). RESULTS: Data from 1016 eyes (511 participants) across 74 sites were analyzed. The mean VA measurements were 68.6 letters (Snellen equivalent 20/50) at the clinical visit and 76.3 letters (Snellen equivalent 20/32) at the protocol visit, with a mean (standard deviation [SD]) of 26 (21) days between visits. Mean (SD) protocol VA was better than clinical VA by 7.6 (9.6) letters overall, 10.7 (12.6) letters in eyes with clinical VA <= 20/50 (n\&nbsp;= 376), and 5.8 (6.6) letters in eyes with clinical VA >= 20/40 (n\&nbsp;= 640). On average, the difference between clinical and protocol VA was 1.3 letters smaller for every 1-line (5 letters) increase in clinical VA (P \&lt; 0.001). Mean (SD) differences by clinical correction of refractive error were 3.9 (9.0) letters with refraction, 6.9 (9.2) letters with glasses/contact lenses, 7.9 (11.5) letters with pinhole, and 9.8 (9.3) letters without correction (P\&nbsp;= 0.06). CONCLUSIONS: On average, clinical Snellen VA is 1 to 2 lines worse than eETDRS protocol refraction and VA testing, which may partly explain why clinical practice does not always replicate clinical trial results. Eyes with lower clinical measurements and eyes tested without clinical refraction tended to have larger differences. Considering the potential discrepancies between clinical and protocol VA measurements, refracting eyes in the clinic may benefit patients when determining treatment plans and study referrals based on vision. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Angiogenesis Inhibitors, Diabetic Retinopathy, Humans, Intravitreal Injections, Macular Edema, Retina, Retrospective Studies, Visual Acuity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.12.008},
	author = {Baker, Carl W and Josic, Kristin and Maguire, Maureen G and Jampol, Lee M and Martin, Daniel F and Rofagha, Soraya and Sun, Jennifer K and DRCR Retina Network}
}
@article {1474200,
	title = {Design and Outcomes of a Novel Keratoprosthesis: Addressing Unmet Needs in End-Stage Cicatricial Corneal Blindness},
	journal = {Cornea},
	volume = {39},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {484-490},
	abstract = {PURPOSE: The most commonly applied prosthetic devices for corneal blindness in the setting of severe cicatricial keratoconjunctivitis are the Boston keratoprosthesis type II and the modified osteo-odonto-keratoprosthesis, with these requiring either normal eyelid skin or a healthy cuspid tooth, respectively. For patients with neither attribute, we developed a new keratoprosthesis device combining positive aspects of both Boston keratoprosthesis type II and modified osteo-odonto-keratoprosthesis, which we have named the "Lux." METHODS: Short-term postoperative outcomes for the Lux keratoprosthesis, best-corrected visual acuity (BCVA), device retention, and complications, were examined in a retrospective case series of 9 eyes of 9 patients implanted at 4 centers. RESULTS: Seven of 9 (77.8\%) eyes had cicatricial corneal blindness due to autoimmune disease and 2 (22.2\%) from severe burns. Preoperative BCVA was <=hand motions in all patients. Three (33.3\%) had previously received at least 1 keratoprosthesis in the affected eye, and 4 (44.4\%) had previously undergone >=1 therapeutic keratoplasty. One patient had 19 previous eye surgeries. The mean duration of postoperative follow-up was 18.7 months (range 7-28 months). BCVA of >=20/200 was achieved in all 9 patients, with 2 (22.2\%) reaching 20/20 at the last examination, and all 9 (100\%) of the devices were retained. One recipient developed a retinal detachment 2 months after implantation. Two (22.2\%) patients required placement of a glaucoma drainage device. CONCLUSIONS: The Lux keratoprosthesis was developed for patients with severe cicatricial keratoconjunctivitis who were otherwise not candidates for existing keratoprosthesis designs. Short-term outcomes after implantation of the Lux keratoprosthesis were encouraging.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002207},
	author = {Bakshi, Shaunak K and Graney, John and Paschalis, Eleftherios I and Agarwal, Shweta and Basu, Sayan and Iyer, Geetha and Liu, Christopher and Srinivasan, Bhaskar and Chodosh, James}
}
@article {1517208,
	title = {Training in the year of the eye: the impact of the COVID-19 pandemic on ophthalmic education},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {9},
	year = {2020},
	month = {2020 09},
	pages = {1181-1183},
	keywords = {Betacoronavirus, Coronavirus Infections, Education, Medical, Graduate, Humans, Internship and Residency, Ophthalmology, Pandemics, Pneumonia, Viral, Telemedicine},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316991},
	author = {Bakshi, Shaunak K and Ho, Allen C and Chodosh, James and Fung, Adrian T and Chan, R V Paul and Ting, Daniel Shu Wei}
}
@article {1528401,
	title = {The era of artificial intelligence and virtual reality: transforming surgical education in ophthalmology},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {10},
	year = {2021},
	month = {2021 Oct},
	pages = {1325-1328},
	abstract = {Training the modern ophthalmic surgeon is a challenging process. Microsurgical education can benefit from innovative methods to practice surgery in low-risk simulations, assess and refine skills in the operating room through video content analytics, and learn at a distance from experienced surgeons. Developments in emerging technologies may allow us to pursue novel forms of instruction and build on current educational models. Artificial intelligence, which has already seen numerous applications in ophthalmology, may be used to facilitate surgical tracking and evaluation. Within immersive technology, growth in the space of virtual reality head-mounted displays has created intriguing possibilities for operating room simulation and observation. Here, we explore the applications of these technologies and comment on their future in ophthalmic surgical education.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316845},
	author = {Bakshi, Shaunak K and Lin, Shawn R and Ting, Daniel Shu Wei and Chiang, Michael F and Chodosh, James}
}
@article {1417549,
	title = {Lucia and Beyond: Development of an Affordable Keratoprosthesis},
	journal = {Cornea},
	volume = {38},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {492-497},
	abstract = {PURPOSE: Severe corneal disease contributes significantly to the global burden of blindness. Corneal allograft surgery remains the most commonly used treatment, but does not succeed long term in every patient, and the odds of success fall with each repeated graft. The Boston keratoprosthesis type I has emerged as an alternative to repeat corneal allograft. However, cost limits its use in resource-poor settings, where most corneal blind individuals reside. METHODS: All aspects of the Boston keratoprosthesis design process were examined to determine areas of potential modification and simplification, with dual goals to reduce cost and improve the cosmetic appearance of the device in situ. RESULTS: Minor modifications in component design simplified keratoprosthesis manufacturing. Proportional machinist time could be further reduced by adopting a single axial length for aphakic eyes, and a single back plate diameter. The cosmetic appearance was improved by changing the shape of the back plate holes from round to radial, with a petaloid appearance, and by anodization of back plate titanium to impute a more natural color. CONCLUSIONS: We have developed a modified Boston keratoprosthesis type I, which we call the "Lucia." The Lucia retains the 2 piece design and ease of assembly of the predicate device, but would allow for manufacturing at a reduced cost. Its appearance should prove more acceptable to implanted patients. Successful keratoprosthesis outcomes require daily medications for the life of the patient and rigorous, frequent, postoperative care. Effective implementation of the device in resource-poor settings will require further innovations in eye care delivery.},
	keywords = {Blindness, Corneal Diseases, Cost Control, Humans, Prostheses and Implants, Prosthesis Design, Prosthesis Implantation},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001880},
	author = {Bakshi, Shaunak K and Paschalis, Eleftherios I and Graney, John and Chodosh, James}
}
@article {1213796,
	title = {Treatment of cystoid macular edema secondary to retinitis pigmentosa: A systematic review},
	journal = {Surv Ophthalmol},
	year = {2017},
	month = {2017 Oct 04},
	abstract = {There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa (RP); however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (CAI) (including acetazolamide, methazolamide) and topical CAI (dorzolamide and brinzolamide) are effective first line treatments. In patients unresponsive to CAI treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implant), oral corticosteroid (Deflazacort), intravitreal anti-vascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to RP. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first line treatment in CME secondary to RP. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2017.09.009},
	author = {Bakthavatchalam, Malini and Lai, Frank H P and Rong, Shi Song and Ng, Danny S and Brelen, Marten E}
}
@article {1559559,
	title = {Pinguecula with spheroidal degeneration: clinicopathologic correlation},
	journal = {Orbit},
	volume = {41},
	number = {1},
	year = {2022},
	month = {2022 Feb},
	pages = {139},
	abstract = {Clinicopathologic correlation of a pinguecula with spheroidal degeneration: a benign entity occasionally encountered in clinical practice.},
	keywords = {Humans, Pinguecula},
	issn = {1744-5108},
	doi = {10.1080/01676830.2020.1863434},
	author = {Bal, Sila and Peggy Chang, Han-Ying and Wolkow, Natalie}
}
@article {1593862,
	title = {Scleral Perforation Secondary to Cyclophotocoagulation},
	journal = {Ophthalmology},
	volume = {128},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {662},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.11.013},
	author = {Bal, Sila and Tahvildari, Maryam and Jurkunas, Ula}
}
@article {1347425,
	title = {Evaluating Retinal Histology Using Multimodal Imaging: A Case Study of Coats Disease},
	journal = {Retina},
	volume = {38},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {e76-e79},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002324},
	author = {Balaratnasingam, Chandrakumar and Parikh, Ravi and Yannuzzi, Lawrence A}
}
@article {382561,
	title = {Expanding the phenotypic spectrum and variability of endocrine abnormalities associated with TUBB3 E410K syndrome.},
	journal = {J Clin Endocrinol Metab},
	volume = {100},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {E473-7},
	abstract = {CONTEXT: A heterozygous de novo c.1228G\&gt;A mutation (E410K) in the TUBB3 gene encoding the neuronal-specific β-tubulin isotype 3 (TUBB3) causes the TUBB3 E410K syndrome characterized by congenital fibrosis of the extraocular muscles (CFEOM), facial weakness, intellectual and social disabilities, and Kallmann syndrome (anosmia with hypogonadotropic hypogonadism). All TUBB3 E410K subjects reported to date are sporadic cases. OBJECTIVE: This study aimed to report the clinical, genetic, and molecular features of a familial presentation of the TUBB3 E410K syndrome. DESIGN: Case report of a mother and three affected children with clinical features of the TUBB3 E410K syndrome. SETTING: Academic Medical Center. MAIN OUTCOME MEASURES: Genetic analysis of the TUBB3 gene and clinical evaluation of endocrine and nonendocrine phenotypes. RESULTS: A de novo TUBB3 c.1228G\&gt;A mutation arose in a female proband who displayed CFEOM, facial weakness, intellectual and social disabilities, and anosmia. However, she underwent normal sexual development at puberty and had three spontaneous pregnancies with subsequent autosomal-dominant inheritance of the mutation by her three boys. All sons displayed nonendocrine features of the TUBB3 E410K syndrome similar to their mother but, in addition, had variable features suggestive of additional endocrine abnormalities. CONCLUSIONS: This first report of an autosomal-dominant inheritance of the TUBB3 c.1228G\&gt;A mutation in a family provides new insights into the spectrum and variability of endocrine phenotypes associated with the TUBB3 E410K syndrome. These observations emphasize the need for appropriate clinical evaluation and complicate genetic counseling of patients and families with this syndrome.},
	issn = {1945-7197},
	doi = {10.1210/jc.2014-4107},
	author = {Balasubramanian, Ravikumar and Chew, Sheena and MacKinnon, Sarah E and Kang, Peter B and Andrews, Caroline and Chan, Wai-Man and Engle, Elizabeth C}
}
@article {1814386,
	title = {Isolated Sixth Nerve Palsy and COVID-19: Response},
	journal = {J Neuroophthalmol},
	year = {2024},
	month = {2024 Mar 08},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000002128},
	author = {Baldwin, Grace and Gaier, Eric D and Hennein, Lauren}
}
@article {1748526,
	title = {Isolated Sixth Nerve Palsy and COVID-19: A Recurrent Case in a 7-Month-Old Child and Analysis of Reported Cases},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 Aug 30},
	abstract = {BACKGROUND: With the SARS-CoV-2 pandemic (COVID-19), data on central and peripheral nervous system involvement, including those causing cranial nerve 6 (CN6) palsy, have been limited to case reports. To extract clinically relevant features of COVID-19-related CN6 palsy, we report on a recurrent pediatric case and analysis of reported cases associated with infection or immunization. METHODS: A PubMed search revealed 18 cases of isolated CN6 palsy in addition to the index case (n = 19). Clinical characteristics, workup, and temporal associations between systemic symptoms onset or vaccination, symptoms onset, and resolution were compiled and analyzed. RESULTS: The median age of CN6 onset was 43 years (interquartile range [IQR]: 28-52). Sixteen cases (84.2\%) were associated with COVID-19 illness and 3 (15.8\%) were associated with COVID-19 vaccination. Four cases (23.5\%) had positive neuroimaging findings. The median latency from first COVID-19 symptoms or vaccination to onset of CN6 palsy was 6 days (IQR: 2.3-16), and the median time from onset to resolution was 30 days (IQR: 14-60). Latency to onset of CN6 palsy was significantly and directly associated with time to resolution (R2 = 0.401, P = 0.010). Patients who had a positive SARS-CoV-2 antibody test had significantly longer days from symptoms to onset (6.0 vs 24.5, P = 0.030), and patients with a positive SARS-CoV-2 polymerase chain reaction test had a significantly shorter time to resolution (17.50 vs 90, P = 0.042). CONCLUSIONS: Isolated CN6 palsy from COVID-19 is rare, can occur in infants as young as 7 months, and can be recurrent. Longer latency from systemic symptoms onset portends greater recovery times, and this relationship may reflect multiple mechanisms by which COVID-19 (and/or an immune response thereto) causes cranial neuropathies with direct clinical relevance.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001989},
	author = {Baldwin, Grace E and Gaier, Eric D and Hennein, Lauren M}
}
@article {1653604,
	title = {A Comparative Study of Traditional Scleral Buckling to a New Technique: Guarded Light Pipe with Heads-Up Three-Dimensional Visualization},
	journal = {Clin Ophthalmol},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {3079-3088},
	abstract = {Purpose: The guarded light pipe is a recently described alternative endoillumination technique to chandelier illumination. We sought to compare the outcomes of scleral buckling (SB) under indirect ophthalmoscopy (ID) to heads-up three-dimensional visualization with a guarded light pipe (3DGLP). Methods: A retrospective comparative study was performed, including 47 eyes that underwent SB for rhegmatogenous retinal detachment (RRD) repair with either traditional ID (n = 31) or 3DGLP (n = 16). Results: The single surgery anatomic success rate was 87.0\% in the ID group and 87.5\% in the 3DGLP group. The final anatomic success rate was 100\% in both groups. The median (interquartile range) post-operative logMAR was 0.10 (0.0-0.20) in the ID group and 0.08 (0.02-0.69) in the 3DGLP group (p = 0.51). The median operative time was 107 (94-123) minutes in the ID group and 100 (90-111) minutes in the 3DGLP group (p = 0.25). Among eyes that underwent subretinal fluid drainage, the operative time was significantly longer in the ID group compared to the 3DGLP group, 113 (100-135) minutes vs 93 (85-111) minutes (p = 0.035). There were no post-operative complications in the ID group and one complication of self-resolving vitreous hemorrhage associated with a malfunctioning cryoprobe in the 3DGLP group (p = 0.34). There were no cases of post-operative cataract progression in either group. Conclusion: Compared to traditional SB, 3DGLP improves ergonomics and educational value with similar anatomical, visual, intra and post-operative outcomes and may result in shorter operative time in cases requiring subretinal fluid drainage.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S378179},
	author = {Baldwin, Grace and Sokol, Jared T and Ludwig, Cassie A and Miller, John B}
}
@article {1709761,
	title = {Structure-function associations between contrast sensitivity and widefield swept-source optical coherence tomography angiography in diabetic macular edema},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {261},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {3113-3124},
	abstract = {PURPOSE: To evaluate the relationship between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics in diabetic macular edema (DME) was the purpose. METHODS: This prospectively enrolled cross-sectional observational study included 61 eyes of 48 patients that were tested with the quantitative CS function (qCSF) test on the same day as imaging with WF SS-OCTA (PLEX{\textregistered} Elite 9000, Carl Zeiss Meditec) 3 {\texttimes} 3, 6 {\texttimes} 6, and 12 {\texttimes} 12\&nbsp;mm scans. Outcomes included visual acuity (VA) and multiple qCSF metrics. Vascular metrics included vessel density (VD) and vessel skeletonized density (VSD) in the superficial (SCP) and deep capillary plexus (DCP) and whole retina (WR) and foveal avascular zone (FAZ) parameters. Mixed effects multivariable linear regression models controlling for age, lens status, and diabetic retinopathy stage were performed. Standardized beta coefficients were calculated by refitting the standardized data. RESULTS: SS-OCTA metrics had a significant association with CS and VA. The effect size of OCTA metrics was larger on CS compared to VA. For example, the standardized beta coefficients for VSD and CS at 3\&nbsp;cpd (βSCP = 0.76, βDCP = 0.71, βWR = 0.72, p \&lt; 0.001) were larger than those for VA (βSCP =  - 0.55, p \&lt; 0.001; βDCP =  - 0.43, p = 0.004; βWR =  - 0.50, p \&lt; 0.001). On 6 {\texttimes} 6\&nbsp;mm images, AULCSF, CS at 3\&nbsp;cpd, and CS at 6\&nbsp;cpd were significantly associated with VD and VSD in all three slab types (SCP, DCP, and WR), while VA was not. CONCLUSION: Structure-function associations in patients with DME leveraging the qCSF device suggest microvascular changes on WF SS-OCTA are associated with larger changes in contrast sensitivity than VA.},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06086-1},
	author = {Baldwin, Grace and Vingopoulos, Filippos and Garg, Itika and Moon, Jade Y and Zeng, Rebecca and Cui, Ying and Katz, Raviv and Le, Rongrong and Lu, Edward S and Sayah, Diane N and Hassan, Zakariyya and Kim, Leo A and Tobias Elze and Husain, Deeba and Miller, John B}
}
@article {1580494,
	title = {Gene editing technology: Towards precision medicine in inherited retinal diseases},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {176-184},
	abstract = {Purpose: To review preclinical and clinical advances in gene therapy, with a focus on gene editing technologies, and application to inherited retinal disease.Methods: A narrative overview of the literature, summarizing the state-of-the-art in clinical gene therapy for inherited retinal disease, as well as the science and application of new gene editing technology.Results: The last three years has seen the first FDA approval of an in vivo gene replacement therapy for a hereditary blinding eye disease and, recently, the first clinical application of an in vivo gene editing technique. Limitations and challenges in this evolving field are highlighted, as well as new technologies developed to address the multitude of molecular mechanisms of disease.Conclusion: Genetic therapy for the treatment of inherited retinal disease is a rapidly expanding area of ophthalmology. New technologies have revolutionized the field of genome engineering and rekindled an interest in precision medicines for these conditions.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1887903},
	author = {Ballios, Brian G and Pierce, Eric A and Huckfeldt, Rachel M}
}
@article {913396,
	title = {Patterns of Retinal Nerve Fiber Layer Loss in Different Subtypes of Open Angle Glaucoma Using Spectral Domain Optical Coherence Tomography.},
	journal = {J Glaucoma},
	volume = {25},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {865-872},
	abstract = {PURPOSE OF THE STUDY: The purpose of the study was to determine whether there are different patterns of retinal nerve fiber layer (RNFL) thinning as measured by spectral domain optical coherence tomography (SD-OCT) for 4 subtypes of open angle glaucoma (OAG): primary OAG (POAG), normal tension glaucoma (NTG), pseudoexfoliation glaucoma (PXG), and pigmentary glaucoma (PDG) and to compare them with normal controls. MATERIALS AND METHODS: SD-OCT RNFL thickness values were measured for 4 quadrants and for 4 sectors (ie, superior-nasal, superior-temporal, inferior-nasal, and inferior-temporal). Differences in RNFL thickness values between groups were analyzed using analysis of variance. Paired t tests were used for quadrant comparisons. RESULTS: Two hundred eighty-five participants (102 POAG patients, 33 with NTG, 48 with PXG, 13 with PDG, and 89 normal patients) were included in this study. All 4 subtypes of OAG showed significant RNFL thinning in the superior, inferior, and nasal quadrants as well as the superior-temporal and inferior-temporal sectors (all P-values \&lt;0.0001) compared with normals. POAG and NTG patients had greater RNFL thinning inferiorly and inferior-temporally than superiorly (P-values: 0.002 to 0.018 and 0.006, respectively) compared with PXG patients. In contrast, PDG patients had greater RNFL thinning superiorly and superior-nasally than inferiorly compared with other OAG subtypes (ie, POAG, NTG, PXG groups, with P-values: 0.009, 0.003, 0.009, respectively). Of the 4 OAG subtypes, PXG patients exhibited the greatest degree of inter-eye RNFL asymmetry. CONCLUSIONS: This study suggests that SD-OCT may be able to detect significant differences in patterns of RNFL thinning for different subtypes of OAG.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000534},
	author = {Baniasadi, Neda and Paschalis, Eleftherios I and Haghzadeh, Mahdi and Ojha, Pallavi and Tobias Elze and Mahd, Mufeed and Chen, Teresa C}
}
@article {1125261,
	title = {Associations between Optic Nerve Head-Related Anatomical Parameters and Refractive Error over the Full Range of Glaucoma Severity},
	journal = {Transl Vis Sci Technol},
	volume = {6},
	number = {4},
	year = {2017},
	month = {2017 Jul},
	pages = {9},
	abstract = {PURPOSE: To evaluate the associations between optic disc (OD)-related anatomical parameters (interartery angle [IAA] between superior and inferior temporal retinal arteries, OD tilt [TL], rotation [ROT], and torsion [TO], OD surface curvature [CUR], and central retinal vessel trunk entry point location [CRVTL] on OD) and the spherical equivalent of refractive error (SE), and to assess the impact of glaucoma severity on these relationships. METHODS: Cirrus optical coherence tomography (OCT) fundus images and 24-2 visual fields of 438 patients were included. Ellipses were fitted to OD borders. IAA was calculated between marked retinal artery locations on a circle around OD. Blood vessel entry point on OD was marked to locate CRVTL. TL was measured as the angle between the lines fitted to OD clinical boundary and the Bruch{\textquoteright}s membrane edges on the horizontal B-scans. Ellipse rotation relative to the vertical axis defined ROT. Angle between the long axis of OD and the interartery line defined TO. CUR was determined by the inner limiting membrane on the horizontal B-scans. Linear regression models evaluated by Bayes Factors (BF) were used to determine the covariance structure between the parameters and SE as well as possible impacts of mean deviation (MD). RESULTS: Our results showed that CRVTL had the strongest relationship with SE, followed by ROT, TL, and IAA (BFs: 3.59 {\texttimes} 10(7), 2645, 1126, and 248, respectively). MD did not significantly modulate the relationship between ONH parameters and SE. CONCLUSION: Our results suggest that SE should be considered when interpreting the OD and its circumpapillary region for diagnostic purposes. TRANSLATIONAL RELEVANCE: The reported relationships between OD-related parameters and ametropia may help to decrease false-positive clinical diagnoses of optic neuropathies.},
	issn = {2164-2591},
	doi = {10.1167/tvst.6.4.9},
	author = {Baniasadi, Neda and Wang, Mengyu and Wang, Hui and Mahd, Mufeed and Tobias Elze}
}
@article {1439845,
	title = {The role of routine nasolacrimal sac biopsy during endoscopic dacryocystorhinostomy},
	journal = {Laryngoscope},
	volume = {130},
	number = {3},
	year = {2020},
	month = {2020 Mar},
	pages = {584-589},
	abstract = {OBJECTIVES/HYPOTHESIS: Most patients who undergo endoscopic dacryocystorhinostomy (DCR) have a diagnosis of idiopathic nasolacrimal duct obstruction. The purpose of this study was to examine the impact of routine biopsy of the lacrimal sac performed at time of DCR on subsequent patient diagnosis and treatment. STUDY DESIGN: Retrospective review. METHODS: The histopathology of nasolacrimal specimens (n = 769), obtained from 654 consecutive patients undergoing endoscopic DCR by a single surgeon over a 30-year period, were reviewed. Specific focus included the identification of unanticipated pathologic findings as they related to pertinent patient demographics, clinical presentation, radiologic findings, and intraoperative observations. RESULTS: The study population was 69.6\% female, with an average age of 56.1 {\textpm} 18.2 years. Pathological findings of tissue from the nasolacrimal sac, which was routinely sampled in all cases, showed inflammation (n = 566 [73.6\%]), normal histology (n = 147 [19.1\%]), granulomas (n = 8 [1.0\%]), and neoplastic process (n = 7 [0.9\%]). Patient history, preoperative CT scan, and/or intraoperative findings alerted the surgeon to the possibility of an unusual diagnosis in 12 of the 15 patients. An unsuspected neoplastic or granulomatous cause of lacrimal obstruction was identified on intraoperative biopsy in three patients (0.46\%). CONCLUSIONS: Although neoplastic and granulomatous diseases are relatively rare causes of lacrimal obstruction necessitating DCR surgery, they may be identified by through patient evaluation in most cases and by routine intraoperative biopsy of the lacrimal sac in all cases. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:584-589, 2020.},
	issn = {1531-4995},
	doi = {10.1002/lary.28070},
	author = {Banks, Catherine and Scangas, George A and Husain, Qasim and Hatton, Mark P and Fullerton, Zoe and Metson, Ralph}
}
@article {1470974,
	title = {Development of a Modular Cadaveric Endoscopic Orbital Surgery Model},
	journal = {Am J Rhinol Allergy},
	volume = {34},
	number = {2},
	year = {2020},
	month = {2020 Mar},
	pages = {183-188},
	issn = {1945-8932},
	doi = {10.1177/1945892419882553},
	author = {Banks, Catherine and Husain, Qasim and Sacks, Raymond and Freitag, Suzanne K and Bleier, Benjamin S}
}
@article {1615214,
	title = {Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography},
	journal = {Schizophr Bull},
	volume = {48},
	number = {1},
	year = {2022},
	month = {2022 Jan 21},
	pages = {80-89},
	abstract = {BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 {\texttimes} 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.},
	issn = {1745-1701},
	doi = {10.1093/schbul/sbab111},
	author = {Bannai, Deepthi and Adhan, Iniya and Katz, Raviv and Kim, Leo A and Keshavan, Matcheri and Miller, John B and Lizano, Paulo}
}
@article {1364583,
	title = {Temporal stability of visually selective responses in intracranial field potentials recorded from human occipital and temporal lobes},
	journal = {J Neurophysiol},
	volume = {108},
	number = {11},
	year = {2012},
	month = {2012 Dec},
	pages = {3073-86},
	abstract = {The cerebral cortex needs to maintain information for long time periods while at the same time being capable of learning and adapting to changes. The degree of stability of physiological signals in the human brain in response to external stimuli over temporal scales spanning hours to days remains unclear. Here, we quantitatively assessed the stability across sessions of visually selective intracranial field potentials (IFPs) elicited by brief flashes of visual stimuli presented to 27 subjects. The interval between sessions ranged from hours to multiple days. We considered electrodes that showed robust visual selectivity to different shapes; these electrodes were typically located in the inferior occipital gyrus, the inferior temporal cortex, and the fusiform gyrus. We found that IFP responses showed a strong degree of stability across sessions. This stability was evident in averaged responses as well as single-trial decoding analyses, at the image exemplar level as well as at the category level, across different parts of visual cortex, and for three different visual recognition tasks. These results establish a quantitative evaluation of the degree of stationarity of visually selective IFP responses within and across sessions and provide a baseline for studies of cortical plasticity and for the development of brain-machine interfaces.},
	keywords = {Adolescent, Adult, Brain Waves, Child, Epilepsy, Evoked Potentials, Visual, Female, Humans, Male, Occipital Lobe, Photic Stimulation, Recognition (Psychology), Temporal Lobe, Time Factors, Visual Perception},
	issn = {1522-1598},
	doi = {10.1152/jn.00458.2012},
	author = {Bansal, Arjun K and Singer, Jedediah M and Anderson, William S and Golby, Alexandra and Madsen, Joseph R and Kreiman, Gabriel}
}
@article {1351136,
	title = {Neural dynamics underlying target detection in the human brain},
	journal = {J Neurosci},
	volume = {34},
	number = {8},
	year = {2014},
	month = {2014 Feb 19},
	pages = {3042-55},
	abstract = {Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses.},
	keywords = {Adolescent, Adult, Attention, Brain, Child, Data Interpretation, Statistical, Electrodes, Implanted, Electroencephalography, Epilepsy, Eye Movements, Female, Goals, Humans, Male, Middle Aged, Photic Stimulation, Psychomotor Performance, Recognition (Psychology), Visual Cortex, Visual Perception, Young Adult},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.3781-13.2014},
	author = {Bansal, Arjun K and Madhavan, Radhika and Agam, Yigal and Golby, Alexandra and Madsen, Joseph R and Kreiman, Gabriel}
}
@article {1629452,
	title = {Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins},
	journal = {Cell},
	volume = {185},
	number = {2},
	year = {2022},
	month = {2022 Jan 20},
	pages = {250-265.e16},
	abstract = {Methods to deliver gene editing agents in\&nbsp;vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78\% following 63\% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In\&nbsp;vitro and in\&nbsp;vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2021.12.021},
	author = {Banskota, Samagya and Raguram, Aditya and Suh, Susie and Du, Samuel W and Davis, Jessie R and Choi, Elliot H and Wang, Xiao and Nielsen, Sarah C and Newby, Gregory A and Randolph, Peyton B and Osborn, Mark J and Kiran Musunuru and Palczewski, Krzysztof and Liu, David R}
}
@article {1688371,
	title = {Biometric Risk Factors for Angle Closure Progression After Laser Peripheral Iridotomy},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {6},
	year = {2023},
	month = {2023 Jun 01},
	pages = {516-524},
	abstract = {IMPORTANCE: Laser peripheral iridotomy (LPI) is the most common primary treatment for primary angle closure disease (PACD). However, there are sparse data guiding the longitudinal care of PAC suspect (PACS) eyes after LPI. OBJECTIVE: To elucidate the anatomic effects of LPI that are associated with a protective outcome against progression from PACS to PAC and acute angle closure (AAC) and to identify biometric factors that predict progression after LPI. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of data from the Zhongshan Angle Closure Prevention (ZAP) trial, a study of mainland Chinese people aged 50 to 70 years with bilateral PACS who received LPI in 1 randomly selected eye. Gonioscopy and anterior-segment optical coherence tomography (AS-OCT) imaging were performed 2 weeks after LPI. Progression was defined as the development of PAC or an acute angle closure (AAC) attack. Cohort A included a random mix of treated and untreated eyes, and cohort B included only eyes treated with LPI. Univariable and multivariable Cox regression models were developed to assess biometric risk factors for progression in cohorts A and B. Data were analyzed from January 4 to December 22, 2022. MAIN OUTCOME AND MEASURE: Six-year progression to PAC or AAC. RESULTS: Cohort A included 878 eyes from 878 participants (mean [SD] age, 58.9 [5.0] years; 726 female [82.7\%]) of whom 44 experienced progressive disease. In a multivariable analysis, treatment (hazard ratio [HR], 0.67; 95\% CI, 0.34-1.33; P = .25) was no longer associated with progression after adjusting for age and trabecular iris space area at 500 μm (TISA at 500 μm) at the 2-week visit. Cohort B included 869 treated eyes from 869 participants (mean [SD] age, 58.9 [5.0] years; 717 female [82.5\%]) of whom 19 experienced progressive disease. In multivariable analysis, TISA at 500 μm (HR, 1.33 per 0.01 mm2 smaller; 95\% CI, 1.12-1.56; P = .001) and cumulative gonioscopy score (HR, 1.25 per grade smaller; 95\% CI, 1.03-1.52; P = .02) at the 2-week visit were associated with progression. Persistent angle narrowing on AS-OCT (TISA at 500 μm <=0.05 mm2; HR, 9.41; 95\% CI, 3.39-26.08; P \&lt;.001) or gonioscopy (cumulative score <=6; HR, 2.80; 95\% CI, 1.13-6.93; P =.04) conferred higher risk of progression. CONCLUSIONS AND RELEVANCE: Study results suggest that persistent angle narrowing detected by AS-OCT or cumulative gonioscopy score was predictive of disease progression in PACS eyes after LPI. These findings suggest that AS-OCT and gonioscopy may be performed to identify patients at high risk of developing angle closure who may benefit from closer monitoring despite patent LPI.},
	keywords = {Acute Disease, Biometry, Female, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Iridectomy, Iris, Laser Therapy, Lasers, Middle Aged, Prospective Studies, Retrospective Studies, Tomography, Optical Coherence},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.0937},
	author = {Bao, Yicheng K and Xu, Benjamin Y and Friedman, David S and Cho, Austin and Foster, Paul J and Jiang, Yu and Porporato, Natalia and Pardeshi, Anmol A and Jiang, Yuzhen and Munoz, Beatriz and Aung, Tin and He, Mingguang}
}
@article {987931,
	title = {Evidence-Based Treatment of Diabetic Macular Edema.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	month = {2017},
	pages = {56-66},
	abstract = {Diabetes mellitus is a chronic disease that affects 415 million people worldwide. Despite treatment advances, diabetic eye disease remains a leading cause of vision loss worldwide. Diabetic macular edema (DME) is a common cause of vision loss in diabetic patients. The pathophysiology is complex and involves multiple pathways that ultimately lead to central retinal thickening and, if untreated, visual loss. First-line treatment of DME has evolved from focal/grid laser established by the Early Treatment of Diabetic Retinopathy Study (ETDRS) to intravitreous pharmacologic therapy. Landmark prospective clinical trials examining the effect of intravitreous injections of vascular endothelial growth factor (VEGF) inhibitors in the treatment of DME have demonstrated improved visual outcomes over focal grid laser. This review focuses on the scientific evidence treatment of DME, disease pathophysiology, clinical disease course, current treatment standards, and emerging novel therapeutic approaches.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228388},
	author = {Barham, Rasha and Rami, Hala El and Sun, Jennifer K and Silva, Paolo S}
}
@article {469001,
	title = {Nonlinear Optics: NIR-Triggered Drug Delivery by Collagen-Mediated Second Harmonic Generation (Adv. Healthcare Mater. 8/2015).},
	journal = {Adv Healthc Mater},
	volume = {4},
	number = {8},
	year = {2015},
	month = {2015 Jun},
	pages = {1108},
	abstract = {In the study presented by D. S. Kohane and co-workers on page 1159, fluorescein molecules are initially bound to collagen fibers through UV-sensitive bonds. Collagen fibers are exposed to NIR light, which is upconverted to UV light through second harmonic generation. The UV-sensitive bonds absorb the upconverted UV light and undergo an irreversible cleavage releasing the fluorescein molecules.},
	issn = {2192-2659},
	doi = {10.1002/adhm.201570046},
	author = {Barhoumi, Aoune and Salvador-Culla, Borja and Kohane, Daniel S}
}
@article {469011,
	title = {NIR-Triggered Drug Delivery by Collagen-Mediated Second Harmonic Generation.},
	journal = {Adv Healthc Mater},
	volume = {4},
	number = {8},
	year = {2015},
	month = {2015 Jun},
	pages = {1159-63},
	abstract = {Second harmonic generation is a process through which nonlinear materials such as collagen can absorb two photons and scatter one with twice the energy. Collagen upconverts 730 nm (near-IR) to 365 nm (UV) through second harmonic generation, which cleaves a molecule bound to collagen via a UV-sensitive linker.},
	issn = {2192-2659},
	doi = {10.1002/adhm.201400768},
	author = {Barhoumi, Aoune and Salvador-Culla, Borja and Kohane, Daniel S}
}
@article {1363243,
	title = {Complex cytogenetic rearrangements at the DURS1 locus in syndromic Duane retraction syndrome},
	journal = {Clin Case Rep},
	volume = {1},
	number = {1},
	year = {2013},
	month = {2013 Oct 01},
	issn = {2050-0904},
	doi = {10.1002/ccr3.11},
	author = {Baris, Hagit N and Chan, Wai-Man and Andrews, Caroline and Behar, Doron M and Donovan, Diana J and Morton, Cynthia C and Ranells, Judith and Pal, Tuya and Ligon, Azra H and Engle, Elizabeth C}
}
@article {1608596,
	title = {Granular Cell Tumor of the Orbit: Review of the Literature and a Proposed Treatment Modality},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {2},
	year = {2022},
	month = {2022 Mar-Apr 01},
	pages = {122-131},
	abstract = {PURPOSE: To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit. METHODS: Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities. RESULTS: A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient{\textquoteright}s symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42\%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7\%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage. CONCLUSIONS: GCT should be considered in the differential diagnosis when encountering patients with mass lesions involving the extraocular muscles, peripheral nerves, or less frequently, the optic nerve or orbital apex. Immunohistochemical analysis of biopsied tissue is required for the definitive diagnosis of GCT. Consideration of adjuvant therapies such as proton beam radiation therapy may be appropriate in cases of incomplete surgical resection of benign GCT. Proton beam radiation therapy can be an excellent therapeutic option for symptomatic relief and residual tumor size reduction with an acceptable toxicity profile.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002038},
	author = {Barrantes, Paula Cortes and Zhou, Paul and MacDonald, Shannon M and Ioakeim-Ioannidou, Myrsini and Lee, Nahyoung Grace}
}
@article {1528403,
	title = {Workforce Shortage for Retinopathy of Prematurity Care and Emerging Role of Telehealth and Artificial Intelligence},
	journal = {Pediatr Clin North Am},
	volume = {67},
	number = {4},
	year = {2020},
	month = {2020 08},
	pages = {725-733},
	abstract = {Retinopathy of prematurity (ROP) is the leading cause of childhood blindness in very-low-birthweight and very preterm infants in the United States. With improved survival of smaller babies, more infants are at risk for ROP, yet there is an increasing shortage of providers to screen and treat ROP. Through a literature review of new and emerging technologies, screening criteria, and analysis of a national survey of pediatric ophthalmologists and retinal specialists, the authors found the shortage of ophthalmology workforce for ROP a serious and growing concern. When used appropriately, emerging technologies have the potential to mitigate gaps in the ROP workforce.},
	issn = {1557-8240},
	doi = {10.1016/j.pcl.2020.04.012},
	author = {Barrero-Castillero, Alejandra and Corwin, Brian K and VanderVeen, Deborah K and Wang, Jason C}
}
@article {1435394,
	title = {Update on the Clinical Approach to Spatial Neglect},
	journal = {Curr Neurol Neurosci Rep},
	volume = {19},
	number = {5},
	year = {2019},
	month = {2019 Apr 04},
	pages = {25},
	abstract = {PURPOSE OF REVIEW: Spatial neglect is asymmetric orienting and action after a brain lesion, causing functional disability. It is common after a stroke; however, it is vastly underdocumented and undertreated. This article addresses the implementation gap in identifying and treating spatial neglect, to reduce disability and improve healthcare costs and burden. RECENT FINDINGS: Professional organizations published recommendations to implement spatial neglect care. Physicians can lead an interdisciplinary team: functionally relevant spatial neglect assessment, evidence-based spatial retraining, and integrated spatial and vision interventions can optimize outcomes. Research also strongly suggests spatial neglect adversely affects motor systems. Spatial neglect therapy might thus "kick-start" rehabilitation and improve paralysis recovery. Clinicians can implement new techniques to detect spatial neglect and lead interdisciplinary teams to promote better, integrated spatial neglect care. Future studies of brain imaging biomarkers to detect spatial neglect, and real-world applicability of prism adaptation treatment, are needed.},
	issn = {1534-6293},
	doi = {10.1007/s11910-019-0940-0},
	author = {Barrett, A M and KE Houston}
}
@article {1359919,
	title = {Daptomycin Resistance and Tolerance Due to Loss of Function in Staphylococcus aureus dsp1 and asp23},
	journal = {Antimicrob Agents Chemother},
	volume = {63},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	abstract = {Lipopeptide daptomycin is a last-line cell-membrane-targeting antibiotic to treat multidrug-resistant Alarmingly, daptomycin-resistant isolates have emerged. The mechanisms underlying daptomycin resistance are diverse and share similarities with resistances to cationic antimicrobial peptides and other lipopeptides, but they remain to be fully elucidated. We selected mutants with increased resistance to daptomycin from a library of transposon insertions in sequent type 8 (ST8) HG003. Insertions conferring increased daptomycin resistance were localized to two genes, one coding for a hypothetical lipoprotein (SAOUHSC_00362, Dsp1), and the other for an alkaline shock protein (SAOUHSC_02441, Asp23). Markerless loss-of-function mutants were then generated for comparison. All transposon mutants and knockout strains exhibited increased daptomycin resistance compared to those of wild-type and complemented strains. Null and transposon insertion mutants also exhibited increased resistance to cationic antimicrobial peptides. Interestingly, the mutant also showed increased resistance to vancomycin, a cell-wall-targeting drug with a different mode of action. Null mutations in both and resulted in increased tolerance as reflected by reduced killing to both daptomycin and vancomycin, as well as an increased tolerance to surfactant (Triton X-100). Neither mutant exhibited increased resistance to lysostaphin, a cell-wall-targeting endopeptidase. These findings identified two genes core to the species that make previously uncharacterized contributions to antimicrobial resistance and tolerance in .},
	issn = {1098-6596},
	doi = {10.1128/AAC.01542-18},
	author = {Barros, Elaine M and Martin, Melissa J and Selleck, Elizabeth M and Lebreton, Fran{\c c}ois and Sampaio, Jorge Luiz M and Gilmore, Michael S}
}
@article {1698251,
	title = {Case 14-2023: A 31-Year-Old Man with Redness of the Right Eye},
	journal = {N Engl J Med},
	volume = {388},
	number = {19},
	year = {2023},
	month = {2023 May 11},
	pages = {1800-1810},
	keywords = {Adult, Erythema, Eye, Eye Diseases, Humans, Male},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc2211511},
	author = {Barshak, Miriam B and Dugdale, Caitlin M and Pineda, Roberto}
}
@article {1608588,
	title = {The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial},
	journal = {Ophthalmology},
	volume = {129},
	number = {2},
	year = {2022},
	month = {2022 02},
	pages = {147-158},
	abstract = {PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having >=2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of \&gt;21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7\%) and were women (75.8\%) with mean age of 62.8 {\textpm} 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n\&nbsp;= 24 [5.0\%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n\&nbsp;= 45 [9.4\%]; IR, 21.84 per 1000 eye-years; P\&nbsp;= 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95\% confidence interval [CI], 0.37-0.83; P\&nbsp;= 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95\% CI, 1.03-1.10; P \&lt; 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95\% CI, 1.22-1.50; P \&lt; 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95\% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.},
	keywords = {Aged, Female, Follow-Up Studies, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Iridectomy, Iris, Lasers, Solid-State, Male, Middle Aged, Prospective Studies, Singapore, Tonometry, Ocular, Treatment Outcome, Visual Acuity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.08.017},
	author = {Baskaran, Mani and Kumar, Rajesh S and Friedman, David S and Lu, Qing-Shu and Wong, Hon-Tym and Chew, Paul Tk and Lavanya, Raghavan and Narayanaswamy, Arun and Perera, Shamira A and Foster, Paul J and Aung, Tin}
}
@article {1460356,
	title = {Neuroplastic reorganization in children with ocular and cerebral visual impairment},
	journal = {Dev Med Child Neurol},
	volume = {62},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {16},
	issn = {1469-8749},
	doi = {10.1111/dmcn.14339},
	author = {Bauer, Corinna M}
}
@article {1297782,
	title = {Early blindness is associated with increased volume of the uncinate fasciculus},
	journal = {Eur J Neurosci},
	volume = {47},
	number = {5},
	year = {2018},
	month = {2018 Mar},
	pages = {427-432},
	abstract = {Growing evidence demonstrates dramatic structural and functional neuroplastic changes in individuals born with early-onset blindness. For example, cross-modal sensory processing at the level of the occipital cortex appears to be associated with adaptive behaviors in the blind. However, detailed studies examining the structural properties of key white matter pathways in other regions of the brain remain limited. Given that blind individuals rely heavily on their sense of hearing, we examined the structural properties of two important pathways involved with auditory processing, namely the uncinate and arcuate fasciculi. High angular resolution diffusion imaging (HARDI) tractography was used to examine structural parameters (i.e., tract volume and quantitative anisotropy, or QA) of these two fasciculi in a sample of 13 early blind individuals and 14 normally sighted controls. Compared to controls, early blind individuals showed a significant increase in the volume of the left uncinate fasciculus. A small area of increased QA was also observed halfway along the right arcuate fasciculus in the blind group. These findings contribute to our knowledge regarding the broad neuroplastic changes associated with profound early blindness.},
	issn = {1460-9568},
	doi = {10.1111/ejn.13848},
	author = {Bauer, Corinna M and Cattaneo, Zaira and Merabet, Lotfi B}
}
@article {1302187,
	title = {Multimodal Discrimination between Normal Aging, Mild Cognitive Impairment and Alzheimer{\textquoteright}s Disease and Prediction of Cognitive Decline},
	journal = {Diagnostics (Basel)},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Feb 06},
	abstract = {Alzheimer{\textquoteright}s Disease (AD) and mild cognitive impairment (MCI) are associated with widespread changes in brain structure and function, as indicated by magnetic resonance imaging (MRI) morphometry and 18-fluorodeoxyglucose position emission tomography (FDG PET) metabolism. Nevertheless, the ability to differentiate between AD, MCI and normal aging groups can be difficult. Thus, the goal of this study was to identify the combination of cerebrospinal fluid (CSF) biomarkers, MRI morphometry, FDG PET metabolism and neuropsychological test scores to that best differentiate between a sample of normal aging subjects and those with MCI and AD from the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative. The secondary goal was to determine the neuroimaging variables from MRI, FDG PET and CSF biomarkers that can predict future cognitive decline within each group. To achieve these aims, a series of multivariate stepwise logistic and linear regression models were generated. Combining all neuroimaging modalities and cognitive test scores significantly improved the index of discrimination, especially at the earliest stages of the disease, whereas MRI gray matter morphometry variables best predicted future cognitive decline compared to other neuroimaging variables. Overall these findings demonstrate that a multimodal approach using MRI morphometry, FDG PET metabolism, neuropsychological test scores and CSF biomarkers may provide significantly better discrimination than any modality alone.},
	issn = {2075-4418},
	doi = {10.3390/diagnostics8010014},
	author = {Bauer, Corinna M and Cabral, Howard J and Killiany, Ronald J}
}
@article {314096,
	title = {Neural correlates associated with superior tactile symmetry perception in the early blind},
	journal = {Cortex},
	volume = {63},
	year = {2015},
	month = {2015 Feb},
	pages = {104-117},
	abstract = {Symmetry is an organizational principle that is ubiquitous throughout the visual world. However, this property can also be detected through non-visual modalities such as touch. The role of prior visual experience on detecting tactile patterns containing symmetry remains unclear. We compared the behavioral performance of early blind and sighted (blindfolded) controls on a tactile symmetry detection task. The tactile patterns used were similar in design and complexity as in previous visual perceptual studies. The neural correlates associated with this behavioral task were identified with functional magnetic resonance imaging (fMRI). In line with growing evidence demonstrating enhanced tactile processing abilities in the blind, we found that early blind individuals showed significantly superior performance in detecting tactile symmetric patterns compared to sighted controls. Furthermore, comparing patterns of activation between these two groups identified common areas of activation (e.g. superior parietal cortex) but key differences also emerged. In particular, tactile symmetry detection in the early blind was also associated with activation that included peri-calcarine cortex, lateral occipital (LO), and middle temporal (MT) cortex, as well as inferior temporal and fusiform cortex. These results contribute to the growing evidence supporting superior behavioral abilities in the blind, and the neural correlates associated with crossmodal neuroplasticity following visual deprivation.},
	keywords = {Adult, Blindness, Brain, Brain Mapping, Female, Form Perception, Functional Laterality, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Touch, Touch Perception, Young Adult},
	issn = {1973-8102},
	doi = {10.1016/j.cortex.2014.08.003},
	author = {Bauer, Corinna and Yazzolino, Lindsay and Hirsch, Gabriella and Cattaneo, Zaira and Vecchi, Tomaso and Merabet, Lotfi B}
}
@article {1109766,
	title = {Age-related changes in structural connectivity are improved using subject-specific thresholding},
	journal = {J Neurosci Methods},
	volume = {288},
	year = {2017},
	month = {2017 Aug 15},
	pages = {45-56},
	abstract = {BACKGROUND: Deterministic diffusion tractography obtained from high angular resolution diffusion imaging (HARDI) requires user-defined quantitative anisotropy (QA) thresholds. Most studies employ a common threshold across all subjects even though there is a strong degree of individual variation within groups. We sought to explore whether it would be beneficial to use individual thresholds in order to accommodate individual variance. To do this, we conducted two independent experiments. METHOD: First, tractography of the arcuate fasciculus and network connectivity measures were examined in a sample of 14 healthy participants. Second, we assessed the effects of QA threshold on group differences in network connectivity measures between healthy young (n=19) and old (n=14) individuals. RESULTS: The results of both experiments were significantly influenced by QA threshold. Common thresholds set too high failed to produce sufficient reconstructions in most subjects, thus decreasing the likelihood of detecting meaningful group differences. On the other hand, common thresholds set too low resulted in spurious reconstructions, providing deleterious results. COMPARISON WITH EXISTING METHODS: Subject specific thresholds acquired using our QA threshold selection method (QATS) appeared to provide the most meaningful networks while ensuring that data from all subjects contributed to the analyses. CONCLUSIONS: Together, these results support the use of a subject-specific threshold to ensure that data from all subjects are included in the analyses being conducted.},
	issn = {1872-678X},
	doi = {10.1016/j.jneumeth.2017.06.010},
	author = {Bauer, Corinna M and Zajac, Lauren E and Koo, Bang-Bon and Killiany, Ronald J and Merabet, Lotfi B}
}
@article {1470990,
	title = {Perspectives on Cerebral Visual Impairment},
	journal = {Semin Pediatr Neurol},
	volume = {31},
	year = {2019},
	month = {2019 Oct},
	pages = {1-2},
	issn = {1558-0776},
	doi = {10.1016/j.spen.2019.05.001},
	author = {Bauer, Corinna M and Merabet, Lotfi B}
}
@article {1470987,
	title = {Alterations in the Structural and Functional Connectivity of the Visuomotor Network of Children With Periventricular Leukomalacia},
	journal = {Semin Pediatr Neurol},
	volume = {31},
	year = {2019},
	month = {2019 Oct},
	pages = {48-56},
	abstract = {Children born preterm with periventricular leukomalacia (PVL) demonstrate increased difficulties with tasks requiring visuomotor integration. The visuomotor integration network encompasses brain regions within frontal, parietal, and occipital cortices. Because of their proximity to the lateral ventricle the underlying white matter pathways are at a high risk of damage following PVL-related hypoxic-ischemic white matter injury. This study provides an exploratory analysis of the structural and functional connections within the visuomotor integration network, along with an a priori evaluation of the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and frontal aslant tract. For each pathway, tracts within both hemispheres revealed decreased volume and number of reconstructed fibers and an increase in quantitative anisotropy and generalized fractional anisotropy. The connectivity results also indicate that there may be changes to both the structural integrity and functional integration of neural networks involved with visuomotor integration functions in children with PVL.},
	issn = {1558-0776},
	doi = {10.1016/j.spen.2019.05.009},
	author = {Bauer, Corinna M and Papadelis, Christos}
}
@article {1798476,
	title = {Aberrant White Matter Development in Cerebral Visual Impairment: A Proposed Mechanism for Visual Dysfunction Following Early Brain Injury},
	journal = {J Integr Neurosci},
	volume = {23},
	number = {1},
	year = {2024},
	month = {2024 Jan 10},
	pages = {1},
	abstract = {BACKGROUND: Cerebral visual impairment (CVI) is a common sequala of early brain injury, damage, or malformation and is one of the leading individual causes of visual dysfunction in pediatric populations worldwide. Although patients with CVI are heterogeneous both in terms of underlying etiology and visual behavioural manifestations, there may be underlying similarities in terms of which white matter pathways are potentially altered. This exploratory study used diffusion tractography to examine potential differences in volume, quantitative anisotropy (QA), as well as mean, axial, and radial diffusivities (mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), respectively) focusing on the dorsal and ventral visual stream pathways in a cohort of young adults with CVI compared to typically sighted and developing controls.

METHODS: High angular resolution diffusion imaging (HARDI) data were acquired in a sample of 10 individuals with a diagnosis of CVI (mean age = 17.3 years, 2.97 standard deviation (SD), range 14-22 years) and 17 controls (mean age = 19.82 years, 3.34 SD, range 15-25 years). The inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), vertical occipital fasciculus (VOF), and the three divisions of the superior longitudinal fasciculus (SLF I, II, and III) were virtually reconstructed and average tract volume (adjusted for intracranial volume), MD, AD, and RD were compared between CVI and control groups. As a secondary analysis, an analysis of variance (ANOVA) was carried out to investigate potential differences based on etiology (i.e., CVI due to periventricular leukomalacia (CVI-PVL) and CVI due to other causes (CVI-nonPVL)).

RESULTS: We observed a large degree of variation within the CVI group, which minimized the overall group differences in tractography outcomes when examining the CVI sample as a unitary group. In our secondary analysis, we observed significant reductions in tract volume in the CVI-PVL group compared to both controls and individuals with CVI due to other causes. We also observed widespread significant increases in QA, MD, and AD in CVI-PVL compared to the control group, with mixed effects in the CVI-nonPVL group.

CONCLUSIONS: These data provide preliminary evidence for aberrant development of key white matter fasciculi implicated in visual perceptual processing skills, which are often impaired to varying degrees in individuals with CVI. The results also indicate that the severity and extent of the white matter changes may be due in part to the underlying cause of the cerebral visual impairments. Additional analyses will need to be done in a larger sample alongside behavioural testing to fully appreciate the relationships between white matter integrity, visual dysfunction, and associated causes in individuals with CVI.},
	keywords = {Adolescent, Adult, Brain, Brain Injuries, Child, Diffusion Magnetic Resonance Imaging, Humans, Neural Pathways, Vision Disorders, White Matter, Young Adult},
	issn = {0219-6352},
	doi = {10.31083/j.jin2301001},
	author = {Bauer, Corinna M and Merabet, Lotfi B}
}
@article {284016,
	title = {Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment},
	journal = {J AAPOS},
	volume = {18},
	number = {4},
	year = {2014},
	month = {2014 Aug},
	pages = {398-401},
	abstract = {Cortical (cerebral) visual impairment (CVI) is characterized by visual dysfunction associated with damage to the optic radiations and/or visual cortex. Typically it results from pre- or perinatal hypoxic damage to postchiasmal visual structures and pathways. The neuroanatomical basis of this condition remains poorly understood, particularly with regard to how the resulting maldevelopment of visual processing pathways relates to observations in the clinical setting. We report our investigation of 2 young adults diagnosed with CVI and visual dysfunction characterized by difficulties related to visually guided attention and visuospatial processing. Using high-angular-resolution diffusion imaging (HARDI), we characterized and compared their individual white matter projections of the extrageniculo-striate visual system with a normal-sighted control. Compared to a sighted control, both CVI cases revealed a striking reduction in association fibers, including the inferior frontal-occipital fasciculus as well as superior and inferior longitudinal fasciculi. This reduction in fibers associated with the major pathways implicated in visual processing may provide a neuroanatomical basis for the visual dysfunctions observed in these patients.},
	keywords = {Adolescent, Adult, Diffusion Magnetic Resonance Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Occipital Lobe, Perceptual Disorders, Vision Disorders, Visual Acuity, Visual Pathways, White Matter, Young Adult},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2014.03.004},
	author = {Bauer, Corinna M and Heidary, Gena and Koo, Bang-Bon and Killiany, Ronald J and Bex, Peter and Merabet, Lotfi B}
}
@article {1511508,
	title = {Henle fibre layer haemorrhage: clinical features and pathogenesis},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {3},
	year = {2021},
	month = {2021 Mar},
	pages = {374-380},
	abstract = {BACKGROUND: To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented. METHODS: This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented. RESULTS: Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson{\textquoteright}s syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up. CONCLUSION: The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology {\textquoteright}Henle fiber layer hemorrhage (HH){\textquoteright} is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-315443},
	author = {Baumal, Caroline R and Sarraf, David and Bryant, Tara and Gui, Wei and Muakkassa, Nora and Pichi, Francesco and Querques, Giuseppe and Choudhry, Netan and Teke, Mehmet Yasin and Govetto, Andrea and Invernizzi, Alessandro and Eliott, Dean and Gaudric, Alain and Cunha de Souza, Eduardo and Naysan, Jonathan and Lembo, Andrea and Lee, Grace C and Freund, K Bailey}
}
@article {560276,
	title = {Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye.},
	journal = {PLoS One},
	volume = {10},
	number = {9},
	year = {2015},
	month = {2015},
	pages = {e0138958},
	abstract = {Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0138958},
	author = {Bauskar, Aditi and Mack, Wendy J and Mauris, Jerome and Arg{\"u}eso, Pablo and Heur, Martin and Nagel, Barbara A and Kolar, Grant R and Gleave, Martin E and Nakamura, Takahiro and Kinoshita, Shigeru and Moradian-Oldak, Janet and Panjwani, Noorjahan and Pflugfelder, Stephen C and Wilson, Mark R and Fini, M Elizabeth and Jeong, Shinwu}
}
@article {1363244,
	title = {Risk of choroidal neovascularization among the uveitides},
	journal = {Am J Ophthalmol},
	volume = {156},
	number = {3},
	year = {2013},
	month = {2013 Sep},
	pages = {468-477.e2},
	abstract = {PURPOSE: To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in uveitis cases. DESIGN: Retrospective cohort study. METHODS: Standardized medical record review at 5 tertiary centers. RESULTS: Among 15,137 uveitic eyes (8868 patients), CNV was rare in the cases of anterior or intermediate uveitis. Among the 4041 eyes (2307 patients) with posterior uveitis or panuveitis, 81 (2.0\%) had CNV at presentation. Risk factors included posterior uveitis in general and specific uveitis syndromes affecting the outer retina-retinal pigment epithelium-choroid interface. Among the 2364 eyes (1357 patients) with posterior uveitis or panuveitis and free of CNV at the time of cohort entry, the cumulative 2-year incidence of CNV was 2.7\% (95\% confidence interval [CI], 1.8\% to 3.5\%). Risk factors for incident CNV included currently active inflammation (adjusted hazard ratio [aHR], 2.13; 95\% CI, 1.26 to 3.60), preretinal neovascularization (aHR, 3.19; 95\% CI, 1.30 to 7.80), and prior diagnosis of CNV in the contralateral eye (aHR, 5.79; 95\% CI, 2.77 to 12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada syndrome (aHR, 3.37; 95\% CI, 1.52 to 7.46) and punctate inner choroiditis (aHR, 8.67; 95\% CI, 2.83 to 26.54). Incident CNV was associated with a 2-line loss of visual acuity (+0.19 logarithm of the minimal angle of resolution units; 95\% CI, 0.079 to 0.29) from the preceding visit. CONCLUSIONS: CNV is an uncommon complication of uveitis associated with visual impairment that occurs more commonly in forms affecting the outer retina-retinal pigment epithelium-choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate.},
	keywords = {Adult, Choroidal Neovascularization, Female, Humans, Incidence, Male, Odds Ratio, Prevalence, Retrospective Studies, Risk Assessment, Risk Factors, United States, Uveitis, Vision Disorders, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.04.040},
	author = {Baxter, Sally L and Pistilli, Maxwell and Pujari, Siddharth S and Liesegang, Teresa L and Suhler, Eric B and Thorne, Jennifer E and Foster, C Stephen and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Kempen, John H}
}
@article {1522710,
	title = {Comparison of clinical characteristics of post-refractive surgery-related and post-herpetic neuropathic corneal pain},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 Jul 21},
	abstract = {PURPOSE: To compare the clinical characteristics and in vivo confocal microscopy (IVCM) findings of patients with neuropathic corneal pain (NCP) due to refractive surgery (RS-NCP) and herpetic eye disease (H-NCP) to controls. METHODS: Sixteen patients with RS-NCP and 7 patients with H-NCP, and 37 healthy reference age- and sex-matched healthy controls were included to the study. The medical records were reviewed for demographic features, detailed disease history, ocular surface disease index (OSDI), ocular pain assessment survey (OPAS) scores. IVCM images of patients were analyzed and compared to reference controls by two masked observers. RESULTS: The mean pain intensity score for the last 24 h (5.1 {\textpm} 2.4 vs. 3.9 {\textpm} 1.2; p = 0.27), last 2 weeks (6.1 {\textpm} 2.5 vs. 4.8 {\textpm} 2.3; p = 0.13) for RS-NCP vs. H-NCP respectively, and quality of life scores (p = 0.23) were similar in both groups. Quality of life, especially mood (p = 0.06) and enjoying life/relations to others (p = 0.10) were affected in both groups, but were not statistically significant between groups. The mean total nerve density was lower in RS-NCP (5702.4 {\textpm} 4599.0 μm/mm) compared to their respective controls (26,422.8 {\textpm} 4491.0; p \&lt; 0.001) and in the H-NCP group (2149.5 {\textpm} 2985.9) compared to their respective controls (22,948.8 {\textpm} 3169.0; p \&lt; 0.001). Alterations in DC density were similar between all groups (38.3 {\textpm} 48.0 cells/mm in RS-NCP, 61.0 {\textpm} 76.9 in H-NCP, p = 0.95). CONCLUSION: Neuropathic corneal pain patients due to refractive surgery show similar clinical characteristics, pain levels, quality of life impact, and IVCM findings as patients with NCP due to herpetic eye disease.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.07.006},
	author = {Bayraktutar, Betul N and Ozmen, M Cuneyt and Muzaaya, Nasser and Dieckmann, Gabriela and Koseoglu, N Dilruba and M{\"u}ller, Rodrigo T and Cruzat, Andrea and Cavalcanti, Bernardo M and Hamrah, Pedram}
}
@article {1661825,
	title = {Relationships Between the Cumulative Incidences of Long-term Complications in Type 1 Diabetes: the DCCT/EDIC Study},
	journal = {Diabetes Care},
	year = {2022},
	month = {2022 Dec 15},
	abstract = {OBJECTIVE: To describe the relationships between the cumulative incidences of long-term complications in individuals with type 1 diabetes (T1D) and assess whether observed associations are independent of age, duration of diabetes, and glycemic levels. METHODS: Proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), reduced estimated glomerular filtration rate (eGFR), amputations, cardiovascular disease (CVD), and mortality were assessed in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study over \~{}30 years. RESEARCH DESIGN AND RESULTS: The cumulative incidence of complications ranged from 3\% (amputations) to 37\% (CSME). There were large differences in the cumulative incidence of PDR between participants with versus without prior CSME (66\% vs. 15\%), reduced eGFR (59\% vs. 29\%), and amputation (68\% vs. 32\%); reduced eGFR with or without prior PDR (25\% vs. 9\%), amputation (48\% vs. 13\%), and CVD (30\% vs. 11\%); CVD with or without prior reduced eGFR (37\% vs. 14\%) and amputation (50\% vs. 16\%); and mortality with or without prior reduced eGFR (22\% vs. 9\%), amputation (35\% vs. 8\%), and CVD (25\% vs. 8\%). Adjusted for age, duration of T1D, and mean updated HbA1c, the complications and associations with higher risk included PDR with CSME (hazard ratio [HR] 1.88; 95\% CI 1.42, 2.50), reduced eGFR (HR 1.41; 95\% CI 1.01, 1.97), and CVD (HR 1.43; 95\% CI 1.06, 1.92); CSME with higher risk of PDR (HR 3.94; 95\% CI 3.18 4.89), reduced eGFR (HR 1.49; 95\% CI 1.10, 2.01), and CVD (HR 1.35; 95\% CI 1.03, 1.78); reduced eGFR with higher risk of CVD (HR 2.09; 95\% CI 1.44, 3.03), and death (HR 3.40; 95\% CI 2.35, 4.92); amputation(s) with death (HR 2.97; 95\% CI 1.70, 2.90); and CVD with reduced eGFR (HR 1.59; 95\% CI 1.08, 2.34) and death (HR 1.95; 95\% CI 1.32, 2.90). CONCLUSIONS: Long-term micro- and macrovascular complications and mortality are highly correlated. Age, diabetes duration, and glycemic levels do not completely explain these associations.},
	issn = {1935-5548},
	doi = {10.2337/dc22-1744},
	author = {Bebu, Ionut and Braffett, Barbara H and de Boer, Ian H and Aiello, Lloyd P and Bantle, John P and Lorenzi, Gayle M and Herman, William H and Gubitosi-Klug, Rose A and Perkins, Bruce A and Lachin, John M and Molitch, Mark E and DCCT/EDIC Research Group}
}
@article {1532374,
	title = {Outcomes of primary rhegmatogenous retinal detachment repair with extensive scleral-depressed vitreous removal and dynamic examination},
	journal = {PLoS One},
	volume = {15},
	number = {9},
	year = {2020},
	month = {2020},
	pages = {e0239138},
	abstract = {There are multiple surgical approaches to the repair of rhegmatogenous retinal detachment (RRD). Here, we evaluated the outcomes of small-gauge pars plana vitrectomy (PPV), alone or in combination with scleral buckle (SB-PPV), for RRD repair using a standardized technique by 3 vitreoretinal surgeons: "extensive" removal of the vitreous with scleral depression and dynamic examination of the peripheral retina. One hundred eighty seven eyes of 180 consecutive patients treated for primary RRD by three vitreoretinal surgeons at a tertiary academic medical center from September 2015 to March 2018 were analyzed. Most RRDs occurred in males (134 [71.3\%] eyes), affected the left eye (102 [54.3\%]), and were phakic (119 [63.3\%]). PPV alone was performed in 159 eyes (84.6\%), with a combined SB-PPV used in the remaining 29 eyes (15.4\%); focal endolaser was used in all (100\%) cases. The single surgery anatomic success rate was 186 eyes (99.5\%) at 3 months, and 187 (100\%) at last follow up. Overall best-corrected visual acuity (BCVA) had significantly improved at 3 months ([Snellen 20/47] P\&lt;0.00005) and last follow up ([Snellen 20/31] P\&lt;0.00005), as compared to day of presentation ([Snellen 20/234]). Our findings suggest that "extensive" removal of the vitreous and dynamic peripheral examination with scleral depression may lead to high single surgery success in primary uncomplicated RRD repair.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0239138},
	author = {Begaj, Tedi and Marmalidou, Anna and Papakostas, Thanos D and Diaz, J Daniel and Kim, Leo A and Wu, David M and Miller, John B}
}
@article {1511495,
	title = {A Young Man With Peripheral Vision Loss},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 May 07},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.0566},
	author = {Begaj, Tedi and Lorenzo, Maltish and Miller, John B}
}
@article {341791,
	title = {Infectious endophthalmitis in Boston keratoprosthesis: incidence and prevention},
	journal = {Acta Ophthalmol},
	volume = {92},
	number = {7},
	year = {2014},
	month = {2014 Nov},
	pages = {e546-55},
	abstract = {PURPOSE: To determine the cumulative worldwide incidence of infectious endophthalmitis and associated vision loss after Boston keratoprosthesis (B-KPro) Type I/II implantation and to propose both safe and inexpensive prophylactic antibiotic regimens. METHODS: Two retrospective methods were used to determine the incidence, visual outcomes and aetiologies of infectious endophthalmitis associated with the B-KPro divided per decade: (i) systematic review of the literature from 1990 through January 2013 and (ii) a surveillance survey sent to all surgeons who implanted B-KPros through 2010 with 1-year minimum follow-up. In addition, a single-Boston surgeon 20-year experience was examined. RESULTS: From 1990 through 2010, there were 4729 B-KPros implanted worldwide by 209 U.S. surgeons and 159 international surgeons. The endophthalmitis cumulative mean incidence declined from 12\% during its first decade of use to about 3\% during its second decade in the Unites States and about 5\% internationally during the second decade. There remains a large incidence range both in the United States (1-12.5\%) and internationally (up to 17\%). Poor compliance with daily topical antibiotics is an important risk factor. While Gram-positive organisms remained dominant, fungal infections emerged during the second decade. CONCLUSIONS: Daily prophylactic topical antibiotics have dramatically reduced the endophthalmitis incidence. Although Gram-positive organisms are the most common aetiology, antimicrobials must be inclusive of Gram-negative organisms. Selection of prophylactic regimens should be tailored to local antibiotic susceptibility patterns, be cost-effective, and should not promote the emergence of antimicrobial resistance. An example of a broad-spectrum, low-cost prophylactic option for non-autoimmune patients includes trimethoprim/polymyxinB once daily.},
	keywords = {Antibiotic Prophylaxis, Bioartificial Organs, Cornea, Endophthalmitis, Eye Infections, Bacterial, Eye Infections, Fungal, Global Health, Humans, Incidence, Prosthesis Implantation, Retrospective Studies, Risk Factors, United States, Visual Acuity},
	issn = {1755-3768},
	doi = {10.1111/aos.12309},
	author = {Behlau, Irmgard and Martin, Kathryn V and Martin, Jacqueline N and Naumova, Elena N and Cadorette, James J and Sforza, J Tammy and Pineda, Roberto and Dohlman, Claes H}
}
@article {630246,
	title = {Anterograde or Retrograde Transsynaptic Circuit Tracing in Vertebrates with Vesicular Stomatitis Virus Vectors.},
	journal = {Curr Protoc Neurosci},
	volume = {74},
	year = {2016},
	month = {2016},
	pages = {1.26.1-1.26.27},
	abstract = {Viruses have been used as transsynaptic tracers, allowing one to map the inputs and outputs of neuronal populations, due to their ability to replicate in neurons and transmit in vivo only across synaptically connected cells. To date, their use has been largely restricted to mammals. In order to explore the use of such viruses in an expanded host range, we tested the transsynaptic tracing ability of recombinant vesicular stomatitis virus (rVSV) vectors in a variety of organisms. Successful infection and gene expression were achieved in a wide range of organisms, including vertebrate and invertebrate model organisms. Moreover, rVSV enabled transsynaptic tracing of neural circuitry in predictable directions dictated by the viral envelope glycoprotein (G), derived from either VSV or rabies virus (RABV). Anterograde and retrograde labeling, from initial infection and/or viral replication and transmission, was observed in Old and New World monkeys, seahorses, jellyfish, zebrafish, chickens, and mice. These vectors are widely applicable for gene delivery, afferent tract tracing, and/or directional connectivity mapping. Here, we detail the use of these vectors and provide protocols for propagating virus, changing the surface glycoprotein, and infecting multiple organisms using several injection strategies. {\textcopyright} 2016 by John Wiley \&amp; Sons, Inc.},
	issn = {1934-8576},
	doi = {10.1002/0471142301.ns0126s74},
	author = {Beier, Kevin T and Mundell, Nathan A and Pan, Y Albert and Cepko, Constance L}
}
@article {1363245,
	title = {Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo},
	journal = {Front Neural Circuits},
	volume = {7},
	year = {2013},
	month = {2013},
	pages = {11},
	abstract = {Defining the connections among neurons is critical to our understanding of the structure and function of the nervous system. Recombinant viruses engineered to transmit across synapses provide a powerful approach for the dissection of neuronal circuitry in vivo. We recently demonstrated that recombinant vesicular stomatitis virus (VSV) can be endowed with anterograde or retrograde transsynaptic tracing ability by providing the virus with different glycoproteins. Here we extend the characterization of the transmission and gene expression of recombinant VSV (rVSV) with the rabies virus glycoprotein (RABV-G), and provide examples of its activity relative to the anterograde transsynaptic tracer form of rVSV. rVSV with RABV-G was found to drive strong expression of transgenes and to spread rapidly from neuron to neuron in only a retrograde manner. Depending upon how the RABV-G was delivered, VSV served as a polysynaptic or monosynaptic tracer, or was able to define projections through axonal uptake and retrograde transport. In animals co-infected with rVSV in its anterograde form, rVSV with RABV-G could be used to begin to characterize the similarities and differences in connections to different areas. rVSV with RABV-G provides a flexible, rapid, and versatile tracing tool that complements the previously described VSV-based anterograde transsynaptic tracer.},
	keywords = {Animals, Animals, Newborn, HEK293 Cells, Humans, Membrane Glycoproteins, Mice, Neurons, Organ Culture Techniques, Protein Transport, Rabies virus, Rats, Rats, Sprague-Dawley, Synapses, Viral Envelope Proteins},
	issn = {1662-5110},
	doi = {10.3389/fncir.2013.00011},
	author = {Beier, Kevin T and Saunders, Arpiar B and Oldenburg, Ian A and Sabatini, Bernardo L and Cepko, Constance L}
}
@article {1632287,
	title = {In-office thermal systems for the treatment of dry eye disease},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {5},
	year = {2022},
	month = {2022 Sep-Oct},
	pages = {1405-1418},
	abstract = {Dry eye disease affects millions of people worldwide, causing pain, vision disturbance, and reduced productivity. Meibomian gland dysfunction, a major cause of dry eye, is characterized by chronic glandular inflammation, thickening of the meibum, obstruction of terminal ducts, and glandular atrophy. Treatment of meibomian gland dysfunction can utilize heat and pressure applied to the meibomian glands, increasing meibum expression. With self-treatments, however, not all patients achieve lasting improvement, and compliance is often low. In-office thermal systems offer a second line of treatment and could be a much-needed addition for patients who do not respond to conventional treatment. We critically evaluated the efficacy and safety of LipiFlow, iLux, and TearCare based on existing literature. While the studies found a single in-office thermal treatment to be safe and effective in improving short-term signs and symptoms in patients with dry eye, long-term efficacy needs to be further evaluated. Thus, well-controlled, long-term efficacy studies are warranted to draw clear conclusions. The treatment seemed to provide rapid relief of symptoms that may last up to 1 year, but at a considerably higher cost than the at-home treatments. The choice of treatment depends on cost, compliance with at-home treatment, and personal preference.},
	keywords = {Dry Eye Syndromes, Eyelid Diseases, Humans, Meibomian Gland Dysfunction, Meibomian Glands, Prospective Studies, Tears},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2022.02.007},
	author = {Beining, Marie Wangen and Magn{\o}, Morten Schjerven and Moschowits, Emily and Olafsson, Jonatan and Vehof, Jelle and Dartt, Darlene A. and Utheim, Tor Paaske}
}
@article {1661613,
	title = {Molecular characterization of fungal Endophthalmitis and keratitis caused by yeasts},
	journal = {Med Mycol},
	year = {2022},
	month = {2022 Dec 24},
	abstract = {Candida species are the most common causes of sight-threatening fungal ocular infections in temperate regions of the world. Despite their relevance, little is known about the emergence of novel species and the molecular epidemiology of these infections. Here we molecularly characterized 38 yeast isolates collected from patients diagnosed with endophthalmitis or keratitis at Massachusetts Eye and Ear from 2014-2021. Sequencing of the ITS1-5.8S-/ITS2 regions demonstrated that this population of yeasts was dominated by Candida spp. (37 out of 38; 97\%), with 58\% of the cases caused by C. albicans (n\&nbsp;=\&nbsp;22), and the remaining by emerging non-albicans species, predominantly by C. parapsilosis (n\&nbsp;=\&nbsp;8) and C. dubliniensis (n\&nbsp;=\&nbsp;6). One isolate each was identified as C. tropicalis and Clavispora lusitaniae. Interestingly, all C. dubliniensis were isolated from endophthalmitis and most C. parapsilosis from keratitis. MLST analysis of C. albicans showed a prevalence of CC-1 isolates that has DST69 as the putative founder, with 64\% of them belonging to this clonal complex. Isolates grouped within this cluster were more predominant in endophthalmitis (10 out of 14; 71\%). One C. albicans CC-1 isolate was multi-azole resistant. In conclusion, we observed that nearly half of the ocular infections caused by yeasts are associated with C. albicans, with evidence for the emergence of non-albicans species that are differentially enriched in distinct ocular niches. Candida albicans isolates clustered within the predominant CC-1 group were particularly more common in endophthalmitis, demonstrating a potential pattern of ocular disease enrichment within this clade.},
	issn = {1460-2709},
	doi = {10.1093/mmy/myac099},
	author = {Belanger, Nicole L and Kim, Su Jeoung and Bispo, Paulo J M}
}
@article {1661834,
	title = {Improved Detection of Herpesviruses from Diluted Vitreous Specimens Using Hydrogel Particles},
	journal = {Diagnostics (Basel)},
	volume = {12},
	number = {12},
	year = {2022},
	month = {2022 Dec 01},
	abstract = {Infectious uveitis is a sight-threatening infection commonly caused by herpesviruses. Vitreous humor is often collected for molecular confirmation of the causative agent during vitrectomy and mixed in large volumes of buffered saline, diluting the pathogen load. Here, we explore affinity-capture hydrogel particles (Nanotrap{\textregistered}) to concentrate low abundant herpesviruses from diluted vitreous. Simulated samples were prepared using porcine vitreous spiked with HSV-1, HSV-2, VZV and CMV at 105 copies/mL. Pure undiluted samples were used to test capturing capability of three custom Nanotrap particles (red, white and blue) in a vitreous matrix. We found that all particles demonstrated affinity to the herpesviruses, with the Red Particles having both good capture capability and ease of handling for all herpesviruses. To mimic diluted vitrectomy specimens, simulated-infected vitreous were then serially diluted in 7 mL TE buffer. Diluted samples were subjected to an enrichment protocol using the Nanotrap Red particles. Sensitivity of pathogen detection by qPCR in diluted vitreous increased anywhere between 2.3 to 26.5 times compared to non-enriched specimens. This resulted in a 10-fold increase in the limit of detection for HSV-1, HSV-2 and VZV. These data demonstrated that Nanotrap particles can capture and concentrate HSV-1, HSV-2, VZV and CMV in a vitreous matrix.},
	issn = {2075-4418},
	doi = {10.3390/diagnostics12123016},
	author = {Belanger, Nicole L and Barbero, Robbie and Barclay, Robert and Lepene, Benjamin and Sobrin, Lucia and Bispo, Paulo J M}
}
@article {1598075,
	title = {Teprotumumab and Hearing Loss: Case Series and Proposal for Audiologic Monitoring},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {1},
	year = {2022},
	month = {2022 Jan-Feb 01},
	pages = {73-78},
	abstract = {PURPOSE: To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature. METHODS: Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed. RESULTS: An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients. CONCLUSIONS: Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.},
	keywords = {Antibodies, Monoclonal, Humanized, Hearing Loss, Humans, Prospective Studies, Retrospective Studies},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001995},
	author = {Belinsky, Irina and Creighton, Francis X and Mahoney, Nicholas and Petris, Carisa K and Callahan, Alison B and Campbell, Ashley A and Kazim, Michael and Lee, H B Harold and Yoon, Michael K and Dagi Glass, Lora R}
}
@article {1125266,
	title = {TFOS DEWS II pain and sensation report},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {404-437},
	abstract = {Pain associated with mechanical, chemical, and thermal heat stimulation of the ocular surface is mediated by trigeminal ganglion neurons, while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of meibomian gland secretion or mucin release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in\&nbsp;vivo confocal microscopy.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.05.002},
	author = {Belmonte, Carlos and Nichols, Jason J and Cox, Stephanie M and Brock, James A and Begley, Carolyn G and Bereiter, David A and Dartt, Darlene A. and Galor, Anat and Hamrah, Pedram and Ivanusic, Jason J and Jacobs, Deborah S and McNamara, Nancy A and Rosenblatt, Mark I and Stapleton, Fiona and Wolffsohn, James S}
}
@article {410361,
	title = {Mutational screening of splicing factor genes in cases with autosomal dominant retinitis pigmentosa.},
	journal = {Mol Vis},
	volume = {20},
	year = {2014},
	month = {2014},
	pages = {843-51},
	abstract = {PURPOSE: Mutations in genes encoding proteins from the tri-snRNP complex of the spliceosome account for more than 12\% of cases of autosomal dominant retinitis pigmentosa (adRP). Although the exact mechanism by which splicing factor defects trigger photoreceptor death is not completely clear, their role in retinitis pigmentosa has been demonstrated by several genetic and functional studies. To test for possible novel associations between splicing factors and adRP, we screened four tri-snRNP splicing factor genes (EFTUD2, PRPF4, NHP2L1, and AAR2) as candidate disease genes. METHODS: We screened up to 303 patients with adRP from Europe and North America who did not carry known RP mutations. Exon-PCR and Sanger methods were used to sequence the NHP2L1 and AAR2 genes, while the sequences of EFTUD2 and PRPF4 were obtained by using long-range PCRs spanning coding and non-coding regions followed by next-generation sequencing. RESULTS: We detected novel missense changes in individual patients in the sequence of the genes PRPF4 and EFTUD2, but the role of these changes in relationship to disease could not be verified. In one other patient we identified a novel nucleotide substitution in the 5{\textquoteright} untranslated region (UTR) of NHP2L1, which did not segregate with the disease in the family. CONCLUSIONS: The absence of clearly pathogenic mutations in the candidate genes screened in our cohort suggests that EFTUD2, PRPF4, NHP2L1, and AAR2 are either not involved in adRP or are associated with the disease in rare instances, at least as observed in this study in patients of European and North American origin.},
	keywords = {DNA Mutational Analysis, Genes, Dominant, Genetic Testing, High-Throughput Nucleotide Sequencing, Humans, Open Reading Frames, Peptide Elongation Factors, Retinitis Pigmentosa, Ribonucleoprotein, U4-U6 Small Nuclear, Ribonucleoprotein, U5 Small Nuclear, Ribonucleoproteins, Small Nuclear, RNA Splicing},
	issn = {1090-0535},
	author = {Benaglio, Paola and San Jose, Patricia Fernandez and Avila-Fernandez, Almudena and Ascari, Giulia and Harper, Shyana and Manes, Ga{\"e}l and Ayuso, Carmen and Hamel, Christian and Berson, Eliot L and Rivolta, Carlo}
}
@article {1466911,
	title = {Bilateral Limbus-Sparing Conjunctivitis in a Boy With Rash and Pneumonia},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Sep 12},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.3137},
	author = {Benchetrit, Liliya and van Zyl, Tav{\'e} and Chodosh, James}
}
@article {1573110,
	title = {Vision is protected against blue defocus},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Jan 11},
	pages = {352},
	abstract = {Due to chromatic aberration, blue images are defocused when the eye is focused to the middle of the visible spectrum, yet we normally are not aware of chromatic blur. The eye suffers from monochromatic aberrations which degrade the optical quality of all images projected on the retina. The combination of monochromatic and chromatic aberrations is not additive and these aberrations may interact to improve image quality. Using Adaptive Optics, we investigated the optical and visual effects of correcting monochromatic aberrations when viewing polychromatic grayscale, green, and blue images. Correcting the eye{\textquoteright}s monochromatic aberrations improved optical quality of the focused green images and degraded the optical quality of defocused blue images, particularly in eyes with higher amounts of monochromatic aberrations. Perceptual judgments of image quality tracked the optical findings, but the perceptual impact of the monochromatic aberrations correction was smaller than the optical predictions. The visual system appears to be adapted to the blur produced by the native monochromatic aberrations, and possibly to defocus in blue.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-79911-w},
	author = {Benedi-Garcia, Clara and Vinas, Maria and Dorronsoro, Carlos and Burns, Stephen A and Peli, Eli and Marcos, Susana}
}
@article {1528417,
	title = {Steroid-eluting contact lenses for corneal and intraocular inflammation},
	journal = {Acta Biomater},
	volume = {116},
	year = {2020},
	month = {2020 10 15},
	pages = {149-161},
	abstract = {Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. STATEMENT OF SIGNIFICANCE: Inflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95\% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.},
	issn = {1878-7568},
	doi = {10.1016/j.actbio.2020.08.013},
	author = {Bengani, Lokendrakumar C and Kobashi, Hidenaga and Ross, Amy E and Zhai, Hualei and Salvador-Culla, Borja and Tulsan, Rekha and Kolovou, Paraskevi E and Mittal, Sharad K and Chauhan, Sunil K and Kohane, Daniel S and Ciolino, Joseph B}
}
@article {1125271,
	title = {Activation of mitophagy leads to decline in Mfn2 and loss of mitochondrial mass in Fuchs endothelial corneal dystrophy},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Jul 27},
	pages = {6656},
	abstract = {Human corneal endothelial cells (HCEnCs) are terminally differentiated cells that have limited regenerative potential. The large numbers of mitochondria in HCEnCs are critical for pump and barrier function required for corneal hydration and transparency. Fuchs Endothelial Corneal Dystrophy (FECD) is a highly prevalent late-onset oxidative stress disorder characterized by progressive loss of HCEnCs. We previously reported increased mitochondrial fragmentation and reduced ATP and mtDNA copy number in FECD. Herein, carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced mitochondrial depolarization decreased mitochondrial mass and Mfn2 levels, which were rescued with mitophagy blocker, bafilomycin, in FECD. Moreover, electron transport chain complex (I, V) decrease in FECD indicated deficient mitochondrial bioenergetics. Transmission electron microscopy of FECD tissues displayed an increased number of autophagic vacuoles containing degenerated and swollen mitochondria with cristolysis. An elevation of LC3-II and LAMP1 and downregulation of Mfn2 in mitochondrial fractions suggested that loss of fusion capacity targets fragmented mitochondria to the pre-autophagic pool and upregulates mitophagy. CCCP-induced mitochondrial fragmentation leads to Mfn2 and LC3 co-localization without activation of proteosome, suggesting a novel Mfn2 degradation pathway via mitophagy. These data indicate constitutive activation of mitophagy results in reduction of mitochondrial mass and abrogates cellular bioenergetics during degeneration of post-mitotic cells of ocular tissue.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-06523-2},
	author = {Benischke, Anne-Sophie and Vasanth, Shivakumar and Miyai, Takashi and Katikireddy, Kishore Reddy and White, Tomas and Chen, Yuming and Halilovic, Adna and Price, Marianne and Price, Francis and Liton, Paloma B and Jurkunas, Ula V}
}
@article {1470988,
	title = {The Assessment of Visual Function and Functional Vision},
	journal = {Semin Pediatr Neurol},
	volume = {31},
	year = {2019},
	month = {2019 Oct},
	pages = {30-40},
	abstract = {The complete assessment of vision-related abilities should consider visual function (the performance of components of the visual system) and functional vision (visual task-related ability). Assessment methods are highly dependent upon individual characteristics (eg, the presence and type of visual impairment). Typical visual function tests assess factors such as visual acuity, contrast sensitivity, color, depth, and motion perception. These properties each represent an aspect of visual function and may impact an individual{\textquoteright}s level of functional vision. The goal of any functional vision assessment should be to measure the visual task-related ability under real-world scenarios. Recent technological advancements such as virtual reality can provide new opportunities to improve traditional vision assessments by providing novel objective and ecologically valid measurements of performance, and allowing for the investigation of their neural basis. In this review, visual function and functional vision evaluation approaches are discussed in the context of traditional and novel acquisition methods.},
	issn = {1558-0776},
	doi = {10.1016/j.spen.2019.05.006},
	author = {Bennett, Christopher R and Bex, Peter J and Bauer, Corinna M and Merabet, Lotfi B}
}
@article {1619433,
	title = {Visual search performance in cerebral visual impairment is associated with altered alpha band oscillations},
	journal = {Neuropsychologia},
	volume = {161},
	year = {2021},
	month = {2021 10 15},
	pages = {108011},
	abstract = {Individuals with cerebral visual impairment (CVI) often present with deficits related to visuospatial processing. However, the neurophysiological basis underlying these higher order perceptual dysfunctions have not been clearly identified. We assessed visual search performance using a novel virtual reality based task paired with eye tracking to simulate the exploration of a naturalistic scene (a virtual toy box). This was combined with electroencephalography (EEG) recordings and an analysis pipeline focusing on time frequency decomposition of alpha oscillatory activity. We found that individuals with CVI showed an overall impairment in visual search performance (as indexed by decreased success rate, as well as increased reaction time, visual search area, and gaze error) compared to controls with neurotypical development. Analysis of captured EEG activity following stimulus onset revealed that in the CVI group, there was a distinct lack of strong and well defined posterior alpha desynchronization; an important signal involved in the coordination of neural activity related to visual processing. Finally, an exploratory analysis revealed that in CVI, the magnitude of alpha desynchronization was associated with impaired visual search performance as well as decreased volume of specific thalamic nuclei implicated in visual processing. These results suggest that impairments in visuospatial processing related to visual search in CVI are associated with alterations in alpha band oscillations as well as early neurological injury at the level of visual thalamic nuclei.},
	keywords = {Cognition, Electroencephalography, Humans, Reaction Time, Vision Disorders, Visual Perception},
	issn = {1873-3514},
	doi = {10.1016/j.neuropsychologia.2021.108011},
	author = {Bennett, Christopher R and Bauer, Corinna M and Bex, Peter J and Bottari, Davide and Merabet, Lotfi B}
}
@article {1573116,
	title = {Assessing visual search performance using a novel dynamic naturalistic scene},
	journal = {J Vis},
	volume = {21},
	number = {1},
	year = {2021},
	month = {2021 Jan 04},
	pages = {5},
	abstract = {Daily activities require the constant searching and tracking of visual targets in dynamic and complex scenes. Classic work assessing visual search performance has been dominated by the use of simple geometric shapes, patterns, and static backgrounds. Recently, there has been a shift toward investigating visual search in more naturalistic dynamic scenes using virtual reality (VR)-based paradigms. In this direction, we have developed a first-person perspective VR environment combined with eye tracking for the capture of a variety of objective measures. Participants were instructed to search for a preselected human target walking in a crowded hallway setting. Performance was quantified based on saccade and smooth pursuit ocular motor behavior. To assess the effect of task difficulty, we manipulated factors of the visual scene, including crowd density (i.e., number of surrounding distractors) and the presence of environmental clutter. In general, results showed a pattern of worsening performance with increasing crowd density. In contrast, the presence of visual clutter had no effect. These results demonstrate how visual search performance can be investigated using VR-based naturalistic dynamic scenes and with high behavioral relevance. This engaging platform may also have utility in assessing visual search in a variety of clinical populations of interest.},
	issn = {1534-7362},
	doi = {10.1167/jov.21.1.5},
	author = {Bennett, Christopher R and Bex, Peter J and Merabet, Lotfi B}
}
@article {753676,
	title = {Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial.},
	journal = {Lancet},
	year = {2016},
	month = {2016 Jun 30},
	abstract = {BACKGROUND: Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study. METHODS: In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1{\textperiodcentered}5 {\texttimes} 10(11) vector genomes) in a total volume of 300 μL was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1{\textperiodcentered}71-4{\textperiodcentered}58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389. FINDINGS: No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0{\textperiodcentered}0003, white light full-field sensitivity p\&lt;0{\textperiodcentered}0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0{\textperiodcentered}7398, white light full-field sensitivity p=0{\textperiodcentered}6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p\&gt;0{\textperiodcentered}49 for all time-points compared with baseline). INTERPRETATION: To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease. FUNDING: Center for Cellular and Molecular Therapeutics at The Children{\textquoteright}s Hospital of Philadelphia, Spark Therapeutics, US National Institutes of Health, Foundation Fighting Blindness, Institute for Translational Medicine and Therapeutics, Research to Prevent Blindness, Center for Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M Kirby Foundation, and The Research Foundation-Flanders.},
	issn = {1474-547X},
	doi = {10.1016/S0140-6736(16)30371-3},
	author = {Bennett, Jean and Wellman, Jennifer and Marshall, Kathleen A and McCague, Sarah and Ashtari, Manzar and DiStefano-Pappas, Julie and Elci, Okan U and Chung, Daniel C and Sun, Junwei and Wright, J Fraser and Cross, Dominique R and Aravand, Puya and Cyckowski, Laura L and Bennicelli, Jeannette L and Mingozzi, Federico and Auricchio, Alberto and Pierce, Eric A and Ruggiero, Jason and Leroy, Bart P and Simonelli, Francesca and High, Katherine A and Maguire, Albert M}
}
@article {1109771,
	title = {Spatial updating of multiple targets: Comparison of younger and older adults},
	journal = {Mem Cognit},
	year = {2017},
	month = {2017 Jun 26},
	abstract = {When walking without vision, people mentally keep track of the directions and distances of previously viewed objects, a process called spatial updating. The current experiment indicates that while people across a large age range are able to update multiple targets in memory without perceptual support, aging negatively affects accuracy, precision, and decision time. Participants (20 to 80\&nbsp;years of age) viewed one, three, or six targets (colored lights) on the floor of a dimly lit room. Then, without vision, they walked to a target designated by color, either directly or indirectly (via a forward turning point). The younger adults{\textquoteright} final stopping points were both accurate (near target) and precise (narrowly dispersed), but updating performance did degrade slightly with the number of targets. Older adults{\textquoteright} performance was consistently worse than the younger group, but the lack of interaction between age and memory load indicates that the effect of age on performance was not further exacerbated by a greater number of targets. The number of targets also significantly increased the latency required to turn toward the designated target for both age groups. Taken together, results extend previous work showing impressive updating performance by younger adults, with novel findings showing that older adults manifest small but consistent degradation of updating performance of multitarget arrays.},
	issn = {1532-5946},
	doi = {10.3758/s13421-017-0725-0},
	author = {Bennett, Christopher R and Loomis, Jack M and Klatzky, Roberta L and Giudice, Nicholas A}
}
@article {1773561,
	title = {Inflammatory Mediators of Axon Regeneration in the Central and Peripheral Nervous Systems},
	journal = {Int J Mol Sci},
	volume = {24},
	number = {20},
	year = {2023},
	month = {2023 Oct 19},
	abstract = {Although most pathways in the mature central nervous system cannot regenerate when injured, research beginning in the late 20th century has led to discoveries that may help reverse this situation. Here, we highlight research in recent years from our laboratory identifying oncomodulin (Ocm), stromal cell-derived factor (SDF)-1, and chemokine CCL5 as growth factors expressed by cells of the innate immune system that promote axon regeneration in the injured optic nerve and elsewhere in the central and peripheral nervous systems. We also review the role of ArmC10, a newly discovered Ocm receptor, in mediating many of these effects, and the synergy between inflammation-derived growth factors and complementary strategies to promote regeneration, including deleting genes encoding cell-intrinsic suppressors of axon growth, manipulating transcription factors that suppress or promote the expression of growth-related genes, and manipulating cell-extrinsic suppressors of axon growth. In some cases, combinatorial strategies have led to unprecedented levels of nerve regeneration. The identification of some similar mechanisms in human neurons offers hope that key discoveries made in animal models may eventually lead to treatments to improve outcomes after neurological damage in patients.},
	keywords = {Animals, Axons, Central Nervous System, Humans, Intercellular Signaling Peptides and Proteins, Nerve Regeneration, Neurons, Optic Nerve},
	issn = {1422-0067},
	doi = {10.3390/ijms242015359},
	author = {Benowitz, Larry I and Xie, Lili and Yin, Yuqin}
}
@article {987936,
	title = {Reaching the brain: Advances in optic nerve regeneration.},
	journal = {Exp Neurol},
	volume = {287},
	number = {Pt 3},
	year = {2017},
	month = {2017 Jan},
	pages = {365-373},
	abstract = {The optic nerve has been widely used to investigate factors that regulate axon regeneration in the mammalian CNS. Although retinal ganglion cells (RGCs), the projection neurons of the eye, show little capacity to regenerate their axons following optic nerve damage, studies spanning the 20(th) century showed that some RGCs can regenerate axons through a segment of peripheral nerve grafted to the optic nerve. More recently, some degree of regeneration has been achieved through the optic nerve itself by factors associated with intraocular inflammation (oncomodulin) or by altering levels of particular transcription factors (Klf-4, -9, c-myc), cell-intrinsic suppressors of axon growth (PTEN, SOCS3), receptors to cell-extrinsic inhibitors of axon growth (Nogo receptor, LAR, PTP-σ) or the intracellular signaling pathway activated by these receptors (RhoA). Other regulators of regeneration and cell survival continue to be identified in this system at a rapid pace. Combinatorial treatments that include two or more of these factors enable some retinal ganglion cells to regenerate axons from the eye through the entire length of the optic nerve and across the optic chiasm. In some cases, regenerating axons have been shown to innervate the appropriate central target areas and elicit postsynaptic responses. Many discoveries made in this system have been found to enhance axon regeneration after spinal cord injury. Thus, progress in optic nerve regeneration holds promise not only for visual restoration but also for improving outcome after injury to other parts of the mature CNS.},
	issn = {1090-2430},
	doi = {10.1016/j.expneurol.2015.12.015},
	author = {Benowitz, Larry I and He, Zhigang and Goldberg, Jeffrey L}
}
@article {1773426,
	title = {Evidence-based management of optic neuritis},
	journal = {Curr Opin Ophthalmol},
	year = {2023},
	month = {2023 Oct 17},
	abstract = {PURPOSE OF REVIEW: Optic neuritis can result from several distinct causes, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD), when not idiopathic. This review discusses evidence-based treatment approaches contingent upon each specific cause of optic neuritis. RECENT FINDINGS: Current evidence highlights the need for prompt plasmapheresis as adjunct to intravenous methylprednisolone (IVMP) in patients with NMOSD-associated optic neuritis. Recent advances have included a proliferation of novel disease modifying therapies (DMTs) for long-term management of NMOSD and an understanding of how existing therapeutic options can be leveraged to optimally treat MOGAD. SUMMARY: In acute idiopathic or MS-associated optic neuritis, IVMP hastens visual recovery, though it does not substantially affect final visual outcomes. IVMP and adjunctive plasmapheresis are beneficial in the treatment of NMOSD-associated optic neuritis, with a shorter time-to-treatment associated with a higher likelihood of recovery. The natural history of untreated MOGAD-associated optic neuritis is unclear but treatment with IVMP is near-universal given phenotypic similarities with NMOSD. Long-term immunosuppressive therapy is warranted in patients with NMOSD as well as in patients with MOGAD with poor visual recovery or recurrent attacks.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000001007},
	author = {Bergeron, Emilie and Bouffard, Marc A}
}
@article {1333847,
	title = {Estimation of Diabetic Retinal Microaneurysm Perfusion Parameters Based on Computational Fluid Dynamics Modeling of Adaptive Optics Scanning Laser Ophthalmoscopy},
	journal = {Front Physiol},
	volume = {9},
	year = {2018},
	month = {2018},
	pages = {989},
	abstract = {Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Microaneurysms (MAs), which are abnormal outpouchings of the retinal vessels, are early and hallmark lesions of DR. The presence and severity of MAs are utilized to determine overall DR severity. In addition, MAs can directly contribute to retinal neural pathology by leaking fluid into the surrounding retina, causing abnormal central retinal thickening and thereby frequently leading to vision loss. Vascular perfusion parameters such as shear rate (SR) or wall shear stress (WSS) have been linked to blood clotting and endothelial cell dysfunction, respectively in non-retinal vasculature. However, despite the importance of MAs as a key aspect of diabetic retinal pathology, much remains unknown as to how structural characteristics of individual MAs are associated with these perfusion attributes. MA structural information obtained on high resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) was utilized to estimate perfusion parameters through Computational Fluid Dynamics (CFD) analysis of the AOSLO images. The HemeLB flow solver was used to simulate steady-state and time-dependent fluid flow using both commodity hospital-based and high performance computing resources, depending on the degree of detail required in the simulations. Our results indicate that WSS is lowest in MA regions furthest away from the feeding vessels. Furthermore, areas of low SR are associated with clot location in saccular MAs. These findings suggest that morphology and CFD estimation of perfusion parameters may be useful tools for determining the likelihood of clot presence in individual diabetic MAs.},
	issn = {1664-042X},
	doi = {10.3389/fphys.2018.00989},
	author = {Bernabeu, Miguel O and Lu, Yang and Abu-Qamar, Omar and Aiello, Lloyd P and Sun, Jennifer K}
}
@article {1435395,
	title = {The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome},
	journal = {Hum Mol Genet},
	year = {2019},
	month = {2019 Apr 15},
	abstract = {LOXL1 (lysyl oxidase-like 1) has been identified as the major effect locus in pseudoexfoliation (PEX) syndrome, a fibrotic disorder of the extracellular matrix and frequent cause of chronic open-angle glaucoma. However, all known PEX-associated common variants show allele effect reversal in populations of different ancestry, casting doubt on their biological significance. Based on extensive LOXL1 deep sequencing, we report here the identification of a common noncoding sequence variant, rs7173049A\&gt;G, located downstream of LOXL1, consistently associated with a decrease in PEX risk (OR=0.63, p=6.33x10-31) in nine different ethnic populations. We provide experimental evidence for a functional enhancer-like regulatory activity of the genomic region surrounding rs7173049 influencing expression levels of ISLR2 (immunoglobulin superfamily containing leucine-rich repeat protein 2) and STRA6 (stimulated by retinoic acid receptor 6), apparently mediated by allele-specific binding of the transcription factor THRβ (thyroid hormone receptor beta). We further show that the protective rs7173049-G allele correlates with increased tissue expression levels of ISLR2 and STRA6 and that both genes are significantly downregulated in tissues of PEX patients together with other key components of the STRA6 receptor-driven retinoic acid signaling pathway. siRNA-mediated downregulation of retinoic acid signaling induces upregulation of LOXL1 and PEX-associated matrix genes in PEX-relevant cell types. These data indicate that dysregulation of STRA6 and impaired retinoid metabolismare involved in the pathophysiology of PEX syndrome and that the variant rs7173049-G, which represents the first common variant at the broad LOXL1 locus without allele effect reversal, mediates a protective effect through upregulation of STRA6 in ocular tissues.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddz075},
	author = {Berner, Daniel and Hoja, Ursula and Zenkel, Matthias and Ross, James Julian and Uebe, Steffen and Paoli, Daniela and Frezzotti, Paolo and Rautenbach, Robyn M and Ziskind, Ari and Williams, Susan E and Carmichael, Trevor R and Ramsay, Michele and Topouzis, Fotis and Chatzikyriakidou, Anthi and Lambropoulos, Alexandros and Sundaresan, Periasamy and Ayub, Humaira and Akhtar, Farah and Qamar, Raheel and Zenteno, Juan C and Cruz-Aguilar, Marisa and Astakhov, Yury S and Dubina, Michael and Wiggs, Janey and Ozaki, Mineo and Kruse, Friedrich E and Aung, Tin and Reis, Andr{\'e} and Khor, Chiea Chuen and Pasutto, Francesca and Schl{\"o}tzer-Schrehardt, Ursula}
}
@article {1347426,
	title = {The migraine eye: distinct rod-driven retinal pathways{\textquoteright} response to dim light challenges the visual cortex hyperexcitability theory},
	journal = {Pain},
	volume = {160},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {569-578},
	abstract = {Migraine-type photophobia, most commonly described as exacerbation of headache by light, affects nearly 90\% of the patients. It is the most bothersome symptom accompanying an attack. Using subjective psychophysical assessments, we showed that migraine patients are more sensitive to all colors of light during ictal than during interictal phase and that control subjects do not experience pain when exposed to different colors of light. Based on these findings, we suggested that color preference is unique to migraineurs (as it was not found in control subjects) rather than migraine phase (as it was found in both phases). To identify the origin of this photophobia in migraineurs, we compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual-evoked potential paradigms. Unexpectedly, it was the amplitude of the retinal rod-driven b wave, which was consistently larger (by 14\%-19\% in the light-adapted and 18\%-34\% in the dark-adapted flash ERG) in the migraineurs than in the controls, rather than the retinal cone-driven a wave or the visual-evoked potentials that differs most strikingly between the 2 groups. Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex. Clinically, the findings may explain why migraineurs complain that the light is too bright even when it is dim to the extent that nonmigraineurs feel as if they are in a cave.},
	issn = {1872-6623},
	doi = {10.1097/j.pain.0000000000001434},
	author = {Bernstein, Carolyn A and Nir, Rony-Reuven and Noseda, Rodrigo and Fulton, Anne B and Huntington, Shaelah and Lee, Alice J and Bertisch, Suzanne M and Hovaguimian, Alexandra and Buettner, Catherine and Borsook, David and Burstein, Rami}
}
@article {1474216,
	title = {The Story: Characterization and Cloning of the First Tumor Suppressor Gene},
	journal = {Genes (Basel)},
	volume = {10},
	number = {11},
	year = {2019},
	month = {2019 Nov 01},
	abstract = {The gene is the first described human tumor suppressor gene and plays an integral role in the development of retinoblastoma, a pediatric malignancy of the eye. Since its discovery, the stepwise characterization and cloning of have laid the foundation for numerous advances in the understanding of tumor suppressor genes, retinoblastoma tumorigenesis, and inheritance. Knowledge of led to a paradigm shift in the field of cancer genetics, including widespread acceptance of the concept of tumor suppressor genes, and has provided crucial diagnostic and prognostic information through genetic testing for patients affected by retinoblastoma. This article reviews the long history of gene research, characterization, and cloning, and also discusses recent advances in retinoblastoma genetics that have grown out of this foundational work.},
	issn = {2073-4425},
	doi = {10.3390/genes10110879},
	author = {Berry, Jesse L and Polski, Ashley and Cavenee, Webster K and Dryja, Thaddeus P and Murphree, A Linn and Gallie, Brenda L}
}
@article {603946,
	title = {Synapse Loss and Dendrite Remodeling in a Mouse Model of Glaucoma.},
	journal = {PLoS One},
	volume = {10},
	number = {12},
	year = {2015},
	month = {2015},
	pages = {e0144341},
	abstract = {It has been hypothesized that synaptic pruning precedes retinal ganglion cell degeneration in glaucoma, causing early dysfunction to retinal ganglion cells. To begin to assess this, we studied the excitatory synaptic inputs to individual ganglion cells in normal mouse retinas and in retinas with ganglion cell degeneration from glaucoma (DBA/2J), or following an optic nerve crush. Excitatory synapses were labeled by AAV2-mediated transfection of ganglion cells with PSD-95-GFP. After both insults the linear density of synaptic inputs to ganglion cells decreased. In parallel, the dendritic arbors lost complexity. We did not observe any cells that had lost dendritic synaptic input while preserving a normal or near-normal morphology. Within the temporal limits of these observations, dendritic remodeling and synapse pruning thus appear to occur near-simultaneously.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0144341},
	author = {Berry, Ryan H and Qu, Juan and John, Simon W M and Howell, Gareth R and Jakobs, Tatjana C}
}
@article {931026,
	title = {In Vivo Brillouin Analysis of the Aging Crystalline Lens.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {13},
	year = {2016},
	month = {2016 Oct 1},
	pages = {5093-5100},
	abstract = {Purpose: To analyze the age dependence of the longitudinal modulus of the crystalline lens in vivo using Brillouin scattering data in healthy subjects. Methods: Brillouin scans were performed along the crystalline lens in 56 eyes from 30 healthy subjects aged from 19 to 63 years. Longitudinal elastic modulus was acquired along the sagittal axis of the lens with a transverse and axial resolution of 4 and 60 μm, respectively. The relative lens stiffness was computed, and correlations with age were analyzed. Results: Brillouin axial profiles revealed nonuniform longitudinal modulus within the lens, increasing from a softer periphery toward a stiffer central plateau at all ages. The longitudinal modulus at the central plateau showed no age dependence in a range of 19 to 45 years and a slight decrease with age from 45 to 63 years. A significant intersubject variability was observed in an age-matched analysis. Importantly, the extent of the central stiff plateau region increased steadily over age from 19 to 63 years. The slope of change in Brillouin modulus in the peripheral regions were nearly age-invariant. Conclusions: The adult human lens showed no measurable age-related increase in the peak longitudinal modulus. The expansion of the stiff central region of the lens is likely to be the major contributing factor to age-related lens stiffening. Brillouin microscopy may be useful in characterizing the crystalline lens for the optimization of surgical or pharmacological treatments aimed at restoring accommodative power.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20143},
	author = {Besner, Sebastien and Scarcelli, Giuliano and Pineda, Roberto and Yun, Seok-Hyun}
}
@article {1623343,
	title = {The Historical Evolution of Ocular Tuberculosis: Past, Present, and Future},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Nov 09},
	pages = {1-7},
	abstract = {Ocular involvement is a rare manifestation of tuberculosis. Four key issues historically faced by clinicians when diagnosing and treating ocular tuberculosis - diagnostic uncertainty, naturally heterogeneous presentations, limitations of existing laboratory diagnostic tools, and non-uniform treatment guidelines - continue to test today{\textquoteright}s physicians. Unparalleled scientific and clinical developments over the past century have greatly expanded the knowledge surrounding this challenging ophthalmic condition. Experience with large volumes of cases at tuberculosis-endemic centres has led to recent growth in knowledge and physician experience, perhaps more so in developing countries. Looking forward, the role of diverse new technologies, including artificial intelligence and proteomics, will advance ocular tuberculosis research. Efforts have been made to address the lack of standardized nomenclature, diagnostic uncertainty, and unvalidated, geographically variable treatment guidelines.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2021.1992446},
	author = {Betzler, Bjorn Kaijun and Gunasekeran, Dinesh Visva and Kempen, John and Smith, Justine R and McCluskey, Peter and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali and Agrawal, Rupesh}
}
@article {1655714,
	title = {Anti-tubercular therapy in the treatment of tubercular uveitis: A systematic review and meta-analysis},
	journal = {Surv Ophthalmol},
	volume = {68},
	number = {2},
	year = {2023},
	month = {2023 Mar-Apr},
	pages = {241-256},
	abstract = {We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to \&lt; 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845). Forty-nine studies reporting data for 4,017 TBU patients were included. In comparative studies, the odds ratio (OR) of inflammatory recurrence was 0.33 (95\%CI:0.19-0.60) for TBU patients treated with ATT{\textpm}corticosteroid versus no ATT. For TBU patients treated with ATT{\textpm}corticosteroid, the pooled absolute incidences of inflammatory recurrence, inflammatory reduction, complete resolution of inflammation, and visual acuity improvement were 13\% (n=310/2,216; 95\%CI:9-18), 81\% (n=217/276; 95\%CI: 62-95), 83\% (n=1,167/1,812; 95\%CI: 77-89), and 65\% (n=347/542; 95\%CI:51-78), respectively. Corticosteroids were tapered to \&lt;10 mg/day without inflammatory progression in 91\% (n=326/395; 95\%CI:78-99) of patients, 9\% (n=121/1,376; 95\%CI:6-13) of whom were administered concomitant immunosuppressive agents alongside ATT. We conclude that treatment of TBU with ATT{\textpm}corticosteroid is associated with a high level of control or improvement of inflammation. More prospective studies with detailed reporting of ATT regimens, patient subgroups, and outcomes are required to better evaluate ATT effectiveness.},
	keywords = {Adrenal Cortex Hormones, Antitubercular Agents, Humans, Immunosuppressive Agents, Inflammation, Prospective Studies, Retrospective Studies, Tuberculosis, Ocular, Uveitis},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2022.10.001},
	author = {Betzler, Bjorn Kaijun and Putera, Ikhwanuliman and Testi, Ilaria and Distia Nora, Rina La and Kempen, John and Kon, Onn Min and Pavesio, Carlos and Gupta, Vishali and Agrawal, Rupesh}
}
@article {1363246,
	title = {Congenital megacaruncle: a unique and innocent ocular adnexal anomaly},
	journal = {JAMA Ophthalmol},
	volume = {131},
	number = {12},
	year = {2013},
	month = {2013 Dec},
	pages = {1641-3},
	keywords = {Dermoid Cyst, Eyelid Neoplasms, Goblet Cells, Humans, Male, Middle Aged},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.4401},
	author = {Bever, Gregory J and Jakobiec, Frederick A and Mendoza, Pia R and Hatton, Mark P}
}
@article {1647880,
	title = {Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration},
	journal = {Exp Eye Res},
	volume = {222},
	year = {2022},
	month = {2022 Sep},
	pages = {109170},
	abstract = {Age-related macular degeneration (AMD) is a disease that affects the macula - the central part of the retina. It is a leading cause of irreversible vision loss in the elderly. AMD onset is marked by the presence of lipid- and protein-rich extracellular deposits beneath the retinal pigment epithelium (RPE), a monolayer of polarized, pigmented epithelial cells located between the photoreceptors and the choroidal blood supply. Progression of AMD to the late nonexudative "dry" stage of AMD, also called geographic atrophy, is linked to progressive loss of areas of the RPE, photoreceptors, and underlying choriocapillaris leading to a severe decline in patients{\textquoteright} vision. Differential susceptibility of macular RPE in AMD and the lack of an anatomical macula in most lab animal models has promoted the use of in vitro models of the RPE. In addition, the need for high throughput platforms to test potential therapies has driven the creation and characterization of in vitro model systems that recapitulate morphologic and functional abnormalities associated with human AMD. These models range from spontaneously formed cell line ARPE19, immortalized cell lines such as hTERT-RPE1, RPE-J, and D407, to primary human (fetal or adult) or animal (mouse and pig) RPE cells, and embryonic and induced pluripotent stem cell (iPSC) derived RPE. Hallmark RPE phenotypes, such as cobblestone morphology, pigmentation, and polarization, vary significantly betweendifferent models\&nbsp;and culture conditions used in different labs, which would directly impact their usability for investigating different aspects of AMD biology. Here the AMD Disease Models task group of the Ryan Initiative for Macular Research (RIMR) provides a summary of several currently used in vitro RPE models, historical aspects of their development, RPE phenotypes that are attainable in these models, their ability to model different aspects of AMD pathophysiology, and pros/cons for their use in the RPE and AMD fields. In addition, due to the burgeoning use of iPSC derived RPE cells, the critical need for developing standards for differentiating and rigorously characterizing RPE cell appearance, morphology, and function are discussed.},
	keywords = {Adult, Aged, Animals, Cell Culture Techniques, Geographic Atrophy, Humans, Induced Pluripotent Stem Cells, Macular Degeneration, Mice, Retinal Pigment Epithelium, Swine},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2022.109170},
	author = {Bharti, Kapil and den Hollander, Anneke I and Lakkaraju, Aparna and Sinha, Debasish and Williams, David S and Finnemann, Silvia C and Bowes-Rickman, Catherine and Malek, Goldis and D{\textquoteright}Amore, Patricia A}
}
@article {1302182,
	title = {Alteration in nerves and neurotransmitter stimulation of lacrimal gland secretion in the TSP-1 mouse model of aqueous deficiency dry eye},
	journal = {Mucosal Immunol},
	volume = {11},
	number = {4},
	year = {2018},
	month = {2018 Jul},
	pages = {1138-1148},
	abstract = {The purpose of this study is to determine neural, vascular, protein secretion, and cellular signaling changes with disease progression in lacrimal glands of the thrombospondin-1 (TSP-1) mouse model of dry eye compared to C57BL/6 wild-type (WT) mice. Neural innervation was reduced in TSP-1 lacrimal glands compared to WT controls, whereas the number of blood vessels was increased. Intracellular Ca stores and the amount of lysosomes, mitochondria, and secretory granules, but not the endoplasmic reticulum, were reduced in TSP-1 compared to WT acini at 12 weeks of age. Ex vivo high KCl-evoked secretion was decreased in TSP-1 compared to WT lacrimal gland tissue pieces. The α-adrenergic agonist-stimulated response was increased in TSP-1 at 4 and 24 weeks but decreased at 12 weeks, and the ATP and MeSATP-stimulated peak [Ca] responses were decreased at 24 weeks. These changes were observed prior to the appearance of mononuclear infiltrates. We conclude that in the lacrimal gland the absence of TSP-1: injures peripheral nerves; blocks efferent nerve activation; decreases protein secretion; and alters intracellular Ca stores. Through these effects the absence of TSP-1 leads to disruption of ocular surface homeostasis and development of dry eye.},
	issn = {1935-3456},
	doi = {10.1038/s41385-018-0002-y},
	author = {Bhattacharya, Sumit and Garc{\'\i}a-Posadas, Laura and Hodges, Robin R and Makarenkova, Helen P and Masli, Sharmila and Dartt, Darlene A.}
}
@article {1664959,
	title = {Ophthalmology Residency in the United States: The Case for a National Curriculum},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {167-177},
	abstract = {To identify strategies for effective curriculum development and implementation in United States (US) ophthalmology residency training programs. A literature review was conducted for all English-language PubMed/Medline articles relating to ophthalmology residency education or curriculum/curricula. Despite ACGME-defined program requirements outlining curricular goals for US ophthalmology residency training programs, there is no comprehensive, national curriculum with detailed plans for instruction of necessary topics within the 36-month residency training period. Several articles identify a need for detailed curricula on various topics, propose ideas on how residency programs could create curricula, and explore ways of assessing resident competence. There is a paucity of literature evaluating how ophthalmology residents best learn various ophthalmology topics. We need to develop an intentional, comprehensive, and timely national curriculum for ophthalmology residency programs in the US, with detailed plans on how to meet curricular objectives and consideration of the most effective teaching strategies for different ophthalmology concepts.},
	keywords = {Curriculum, Humans, Internship and Residency, Ophthalmology, United States},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152713},
	author = {Bhullar, Paramjit K and Venkateswaran, Nandini}
}
@article {1645480,
	title = {Neurotrophic Keratopathy in the United States: An Intelligent Research in Sight Registry Analysis},
	journal = {Ophthalmology},
	volume = {129},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {1255-1262},
	abstract = {PURPOSE: To describe the characteristics of neurotrophic keratopathy (NK) in the United States. DESIGN: Retrospective database study. PARTICIPANTS: Thirty-one thousand nine hundred fifteen eyes of 27 483 patients with a diagnosis of NK. METHODS: Retrospective analysis of visits associated with a diagnosis of NK between 2013 and 2018 using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS{\textregistered}) Registry. MAIN OUTCOME MEASURES: Demographic information, prevalence, visual acuity (VA), concomitant diagnosis and procedure codes, and risk factors impacting VA most closely after NK onset date. RESULTS: Mean {\textpm} standard deviation (SD) age at initial diagnosis of NK was 68.0 {\textpm} 16.0 years, and 58.91\% of patients were women (P \&amp;lt; 0.0001). Presentation was unilateral in 58.14\%, bilateral in 16.13\%, and unspecified in 25.73\%. Average 6-year prevalence of NK in the IRIS Registry was 21.34 cases per 100 000 patients. Mean {\textpm} SD VA was 0.60 {\textpm} 0.79 logMAR before diagnosis and 0.88 {\textpm} 0.94 logMAR after diagnosis (P \&amp;lt; 0.0001). Most common concomitant diagnoses included herpetic keratitis (33.70\%), diabetes (31.59\%), and corneal dystrophy (14.28\%). Common procedures for NK management included the use of amniotic membrane (29.90\%), punctal plugs (29.65\%), and bandage contact lenses (22.67\%). Age, male sex, Black race, Hispanic or Latino ethnicity, unilateral involvement, concomitant diagnoses of diabetes, corneal transplantation, and herpetic keratitis were associated significantly with worse VA. CONCLUSIONS: Based on the IRIS Registry, the prevalence of NK is 21.34 cases per 100 000 patients. Visual acuity was significantly worse after NK diagnosis compared with other time points. Neurotrophic keratopathy was associated most commonly with herpetic keratitis and diabetes. Worse VA in patients with NK was associated with several demographic characteristics, history of diabetes, corneal transplantation, and herpetic keratitis.},
	keywords = {Corneal Dystrophies, Hereditary, Female, Humans, Keratitis, Herpetic, Male, Registries, Retrospective Studies, Trigeminal Nerve Diseases, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.06.019},
	author = {Bian, Yandong and Ma, Kevin K and Hall, Nathan E and Tobias Elze and Lorch, Alice and Miller, Joan W and Dana, Reza and Yin, Jia}
}
@article {1559555,
	title = {Gait in Elderly Glaucoma: Impact of Lighting Conditions, Changes in Lighting, and Fear of Falling},
	journal = {Transl Vis Sci Technol},
	volume = {9},
	number = {13},
	year = {2020},
	month = {2020 Dec},
	pages = {23},
	abstract = {Purpose: The purpose of this study was to characterize the impact of lighting changes on gait in elderly patients with glaucoma and evaluate whether associations are mediated by fear of falling (FOF). Methods: Gait initiation and parameters measured with the GAITRite Electronic Walkway were captured in normal indoor light, then in dim light, and again in normal light (normal post dim [NPD]). Participants{\textquoteright} right and left eye visual fields (VFs) were merged into integrated VF (IVF) sensitivities. FOF was evaluated using a Rasch-analyzed questionnaire. Multivariable regression models evaluated whether IVF sensitivity was associated with lighting-dependent gait changes and if this relationship was mediated by FOF. Results: In 213 participants (mean age = 71.4 years), gait initiation in dim light took longer with more VF damage ( = 0.02). Greater VF damage was associated with slower gait in dim ( \&lt; 0.001) and NPD ( = 0.003) lighting, as well as shorter strides ( = 0.02), broader stance ( = 0.003), and more variable stride velocity and length in all lighting (all \&lt; 0.03). When moving from normal to dim lighting, those with more VF damage slowed gait and cadence, shortened stride length, and lengthened double support time (all \&lt; 0.001). Velocity, cadence, and double support time did not return to baseline in NPD lighting (all \&lt; 0.05). Fear of falling did not appear to mediate the relationship between IVF sensitivity and lighting-dependent gait changes. Conclusions: Patients with more VF damage demonstrate gait degradation in extreme or changing lighting, which is not mediated by FOF. Translational Relevance: Quantitative spatiotemporal gait evaluation reveals lighting-associated impairment, supporting patient-reported difficulty with nonideal lighting and equipping providers to advise patients about limitations.},
	issn = {2164-2591},
	doi = {10.1167/tvst.9.13.23},
	author = {Bicket, Amanda K and Mihailovic, Aleksandra and E, Jian-Yu and Nguyen, Angeline and Mukherjee, Moneesha Rani and Friedman, David S and Ramulu, Pradeep Y}
}
@article {1598042,
	title = {Botulinum Toxin Injection for the Treatment of Strabismus: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {128},
	number = {12},
	year = {2021},
	month = {2021 12},
	pages = {1766-1776},
	abstract = {PURPOSE: To review the available evidence comparing the effectiveness of extraocular muscle botulinum toxin type A (BTXA) injection with eye muscle surgery for restoring ocular alignment in children and adults with nonparalytic, nonrestrictive horizontal strabismus. METHODS: Literature searches in the PubMed Cochrane Library, and clinical trial databases with no date restrictions, but limited to articles published in English, were conducted last on January 10, 2021. The searches yielded 515 citations, 40 of which were reviewed in full text by the first author. Fourteen articles met the criteria for inclusion (randomized or nonrandomized comparative studies, or case series with a minimum 50 patients; evaluating extraocular muscle BTXA injection for initial or repeat treatment of horizontal, nonparalytic, nonrestrictive strabismus; with at least 6 months of follow-up) and were graded by a methodologist. RESULTS: The 14 included studies consisted of 2 randomized clinical trials, 3 nonrandomized comparative studies, and 9 case series. All 5 comparative studies were graded level II evidence, and the 9 case series were graded level III evidence. Successful motor outcomes after BTXA injection were relatively consistent across 4 of the 5 comparative studies at 60\%, when adjustment was made for differential selection bias in 1 of the studies. In the 4 studies, successful motor outcomes after surgery ranged from 66\% to 77\% with a mean follow-up of 23 to 75 months, and the outcomes were not significantly different from those after BTXA injection. In the fifth level II study, success was significantly higher with BTXA injection than with surgery (94\% vs. 72\%). The level III BTXA case series demonstrated higher motor success rates of 87\% to 89\% when children were treated in 2 muscles at a time; rates were lower in adults treated with single-muscle BTXA injection. CONCLUSIONS: Extraocular muscle injection of BTXA achieves a high rate of successful motor alignment, comparable with that achieved after eye muscle surgery for nonparalytic, nonrestrictive horizontal strabismus. Good alignment may require multiple BTXA injections, and it is not yet clear whether sensory outcomes are equivalent for BTXA injections versus eye muscle surgery in young children.},
	keywords = {Academies and Institutes, Botulinum Toxins, Type A, Child, Preschool, Female, Humans, Injections, Intramuscular, Male, Neuromuscular Agents, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Ophthalmology, Randomized Controlled Trials as Topic, Strabismus, Technology Assessment, Biomedical, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.05.009},
	author = {Binenbaum, Gil and Chang, Melinda Y and Heidary, Gena and Morrison, David G and Trivedi, Rupal H and Galvin, Jennifer A and Pineles, Stacy L}
}
@article {669301,
	title = {Axial Globe Position Measurement: A Prospective Multicenter Study by the International Thyroid Eye Disease Society.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {2},
	year = {2016},
	month = {2016 Mar-Apr},
	pages = {106-12},
	abstract = {PURPOSE: Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED). METHODS: This is a prospective, international, multicenter, observational study in which 3 types of AGP evaluation were examined: radiologic, clinical, and photographic. In this study, CT was the modality to which all other methods were compared. CT AGP was measured from an orthogonal line between the anterior lateral orbital rims to the cornea. All CT measurements were made at a single institution by 3 individual clinicians. Clinical evaluation was performed with exophthalmometry. Three clinicians from each clinical site assessed AGP with 3 different exophthalmometers and horizontal palpebral width using a ruler. Each physician made 3 separate measurements with each type of exophthalmometer not in succession. All photographic measurements were made at a single institution. AGP was measured from lateral photographs in which a standard marker was placed at the anterior lateral orbital rim. Horizontal and vertical palpebral fissure were measured from frontal photographs. Three trained readers measured 3 separate times not in succession. Exophthalmometry and photography method validity was assessed by agreement with CT (mean differences calculation, intraclass correlation coefficients [ICCs], Bland-Altman figures). Correlation between palpebral fissure and CT AGP was assessed with Pearson correlation. Intraclinician and interclinician reliability was evaluated using ICCs. RESULTS: Sixty-eight patients from 7 centers participated. CT mean AGP was 21.37 mm (15.96-28.90 mm) right and 21.22 mm (15.87-28.70 mm) left (ICC 0.996 and 0.995). Exophthalmometry AGP fell between 18 mm and 25 mm. Intraclinician agreement across exophthalmometers was ideal (ICC 0.948-0.983). Agreement between clinicians was greater than 0.85 for all upright exophthalmometry measurements. Photographic mean AGP was 20.47 mm (10.92-30.88 mm) right and 20.30 mm (8.61-28.72 mm) left. Intrareader and interreader agreement was ideal (ICC 0.991-0.989). All exophthalmometers{\textquoteright} mean differences from CT ranged between -0.06 mm ({\textpm}1.36 mm) and 0.54 mm ({\textpm}1.61 mm); 95\% confidence interval fell within 1 mm. Magnitude of AGP did not affect exophthalmometry validity. Oculus best estimated CT AGP but differences from other exophthalmometers were not clinically meaningful in upright measurements. Photographic AGP (right ICC = 0.575, left ICC = 0.355) and palpebral fissure do not agree with CT. CONCLUSIONS: Upright clinical exophthalmometry accurately estimates CT AGP in TED. AGP measurement was reliably reproduced by the same clinician and between clinicians at multiple institutions using the protocol in this study. These findings allow reliable measurement of AGP that will be of considerable value in future outcome studies.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000437},
	author = {Bingham, Chad M and Sivak-Callcott, Jennifer A and Gurka, Matthew J and Nguyen, John and Hogg, Jeffery P and Feldon, Steve E and Fay, Aaron and Seah, Lay-Leng and Strianese, Diego and Durairaj, Vikram D and Uddin, Jimmy and Devoto, Martin H and Harris, Matheson and Saunders, Justin and Osaki, Tammy H and Looi, Audrey and Teo, Livia and Davies, Brett W and Elefante, Andrea and Shen, Sunny and Realini, Tony and Fischer, William and Kazim, Michael}
}
@article {836766,
	title = {Acquired Corneal Neuropathy and Photoallodynia Associated With Malposition of an Ex-PRESS Shunt.},
	journal = {J Glaucoma},
	volume = {26},
	number = {1},
	year = {2017},
	month = {2017 Jan},
	pages = {e19-e21},
	abstract = {PURPOSE: Corneal neuropathy is a recently described disease process that is not well understood and is likely underdiagnosed as a result. This is the first reported case of an acquired corneal neuropathy associated with malposition of an Ex-PRESS shunt. METHODS: A single case report. RESULTS: We report the case of a 50-year-old man with a history of multiple procedures for glaucoma who subsequently developed photoallodynia and corneal neuropathy in association with malposition of an Ex-PRESS shunt in the peripheral cornea. Laser confocal microscopy (HRT3/RCM) of the cornea showed the presence of neuromas, decreased nerve density, and a significant increase of dendritiform immune cells consistent with our diagnosis. Initial treatment with steroid pulse therapy did not result in decreased inflammation or symptomatic improvement leading to surgical explantation of the shunt. One month after surgery, there was noticeable improvement in the patient{\textquoteright}s pain and photoallodynia (approximately 40\%) as well as the abnormalities seen on confocal microscopy. CONCLUSIONS: We hypothesize that poor Ex-PRESS shunt positioning can act as a nidus for corneal inflammation, resulting in corneal neuropathy and lowering of the nociception threshold.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000502},
	author = {Birnbaum, Faith A and Hamrah, Pedram and Jacobs, Deborah S and Song, Brian J}
}
@article {1603877,
	title = {Microinvasive Glaucoma Surgery: An Evidence-Based Review},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {8},
	year = {2021},
	month = {2021 Nov 17},
	pages = {772-786},
	abstract = {PURPOSE: Interest in micro-invasive glaucoma surgery (MIGS) has exploded over the last 8\&nbsp;years with an increase in MIGS procedures of at least 400\% in the United States, according to Medicare data. MIGS is an umbrella term that can cover many different types of surgeries. This review focuses on peer-reviewed evidence for Trabectome{\textregistered}, iStent inject{\textregistered}, Kahook Dual Blade{\textregistered}, XEN{\textregistered} Gel Stent, and Hydrus{\textregistered}. METHODS: We present key recent studies evaluating the efficacy and safety of MIGS in various types of glaucoma patients with different stages of disease. CONCLUSION: We conclude that MIGS is generally safe and efficacious, although only some MIGS have been studied through randomized clinical trials. When comparing and contrasting the different MIGS procedures, large prospective studies are not yet the norm. High-quality large prospective studies involving MIGS will be an important next step as ophthalmologists decide how to incorporate MIGS into their surgical armamentarium.},
	keywords = {Aged, Glaucoma, Humans, Intraocular Pressure, Medicare, Minimally Invasive Surgical Procedures, Prospective Studies, United States},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1903513},
	author = {Birnbaum, Faith A and Neeson, Cameron and Sol{\'a}-Del Valle, David}
}
@article {314101,
	title = {The corneal micropocket assay: a model of angiogenesis in the mouse eye},
	journal = {J Vis Exp},
	number = {90},
	year = {2014},
	month = {2014 Aug 16},
	abstract = {The mouse corneal micropocket assay is a robust and quantitative in vivo assay for evaluating angiogenesis. By using standardized slow-release pellets containing specific growth factors that trigger blood vessel growth throughout the naturally avascular cornea, angiogenesis can be measured and quantified. In this assay the angiogenic response is generated over the course of several days, depending on the type and dose of growth factor used. The induction of neovascularization is commonly triggered by either basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). By combining these growth factors with sucralfate and hydron (poly-HEMA (poly(2-hydroxyethyl methacrylate))) and casting the mixture into pellets, they can be surgically implanted in the mouse eye. These uniform pellets slowly-release the growth factors over five or six days (bFGF or VEGF respectively) enabling sufficient angiogenic response required for vessel area quantification using a slit lamp. This assay can be used for different applications, including the evaluation of angiogenic modulator drugs or treatments as well as comparison between different genetic backgrounds affecting angiogenesis. A skilled investigator after practicing this assay can implant a pellet in less than 5 min per eye.},
	keywords = {Animals, Cornea, Corneal Neovascularization, Delayed-Action Preparations, Fibroblast Growth Factor 2, Mice, Models, Animal, Neovascularization, Physiologic, Polyhydroxyethyl Methacrylate, Sucralfate, Vascular Endothelial Growth Factor A},
	issn = {1940-087X},
	doi = {10.3791/51375},
	author = {Birsner, Amy E and Benny, Ofra and D{\textquoteright}Amato, Robert J}
}
@article {1632289,
	title = {A Systematic Review of Multi-decade Antibiotic Resistance Data for Ocular Bacterial Pathogens in the United States},
	journal = {Ophthalmol Ther},
	volume = {11},
	number = {2},
	year = {2022},
	month = {2022 Apr},
	pages = {503-520},
	abstract = {INTRODUCTION: Since 2009, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study has been assessing in vitro antibiotic resistance for bacterial isolates sourced from ocular infections in the US. The main goal of this systematic review was to compare in vitro resistance data for ocular pathogens from published US studies with the most recently published data from the ARMOR study (2009-2018) and, where possible, to evaluate trends in bacterial resistance over time over all studies. METHODS: A literature search was conducted using MEDLINE{\textregistered}, BIOSIS Previews{\textregistered}, and EMBASE{\textregistered} databases (1/1/1995-6/30/2021). Data were extracted from relevant studies and antibiotic susceptibility rates for common ocular pathogens (Staphylococcus aureus, coagulase-negative staphylococci [CoNS], Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae), longitudinal changes in susceptibility, and multidrug resistance (MDR) were compared descriptively. RESULTS: Thirty-two relevant studies were identified. High in vitro resistance was found among S. aureus and CoNS to fluoroquinolones, macrolides, and methicillin/oxacillin across studies, with high rates of MDR noted, specifically among methicillin-resistant staphylococci. Data from studies pre-dating or overlapping the early years of ARMOR reflected increasing rates of S.\&nbsp;aureus resistance to fluoroquinolones, macrolides, methicillin/oxacillin, and aminoglycosides, while the ARMOR data suggested slight decreases in resistance to these classes between 2009 and 2018. Overall, methicillin-resistant S.\&nbsp;aureus (MRSA) prevalence peaked from 2005 to 2015 with a possible decreasing trend in more recent years. DISCUSSION AND CONCLUSIONS: Data from local and regional US datasets were generally consistent with data from the national ARMOR surveillance study. Continued surveillance of ocular bacterial pathogens is needed to track trends such as methicillin resistance and MDR prevalence and any new emerging antibiotic resistance phenotypes. Susceptibility data from ARMOR can inform initial choice of therapy, especially in practice areas where local antibiograms are unavailable.},
	issn = {2193-8245},
	doi = {10.1007/s40123-021-00449-9},
	author = {Bispo, Paulo J M and Sahm, Daniel F and Asbell, Penny A}
}
@article {1664986,
	title = {An All-in-One Highly Multiplexed Diagnostic Assay for Rapid, Sensitive, and Comprehensive Detection of Intraocular Pathogens},
	journal = {Am J Ophthalmol},
	volume = {250},
	year = {2023},
	month = {2023 Jun},
	pages = {82-94},
	abstract = {PURPOSE: Intraocular infections are sight-threatening conditions that can lead to vision loss. Rapid identification of the etiologies plays a key role in early initiation of effective therapy to save vision. However, current diagnostic modalities are time consuming and lack sensitivity and inclusiveness. We present here a newly developed comprehensive ocular panel designed to improve diagnostic yields and provide a tool for rapid and sensitive pathogen detection. DESIGN: Experimental laboratory investigation. METHODS: A panel containing 46 pathogens and 2 resistance/virulence markers that are commonly detected in intraocular infections was developed. Genomic targets were scrutinized for stretches predicted to be specific for a particular species while being conserved across different strains. A set of primers for sample enrichment, and two 50mer NanoString compatible probes were then designed for each target. Probe-target hybrids were detected and quantified using the NanoString nCounter SPRINT Profiler. Diagnostic feasibility was assessed in a pilot clinical study testing samples from infectious retinitis (n\&nbsp;=\&nbsp;15) and endophthalmitis (n\&nbsp;=\&nbsp;12) patients, for which the etiologies were confirmed by polymerase chain reaction (PCR) or culture. RESULTS: Analytical studies demonstrated highly sensitive detection of a broad spectrum of pathogens, including bacteria, viruses, and parasites, with limits of detection being as low as 2.5 femtograms per reaction. We also found excellent target specificity, with minimal cross-reactivity detected. The custom-designed NanoString ocular panel correctly identified the causative agent from all clinical specimens positive for a variety of pathogens. CONCLUSION: This highly multiplexed panel for pathogen detection offers a sensitive, comprehensive, and uniform assay run directly on ocular fluids that could significantly improve diagnostics of sight-threatening intraocular infections.},
	keywords = {Bacteria, Endophthalmitis, Eye Infections, Humans, Polymerase Chain Reaction, Sensitivity and Specificity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.01.021},
	author = {Bispo, Paulo J M and Belanger, Nicole and Li, Ashley and Liu, Renee and Susarla, Gayatri and Chan, Weilin and Chodosh, James and Gilmore, Michael S and Sobrin, Lucia}
}
@article {397771,
	title = {Biofilms in infections of the eye.},
	journal = {Pathogens},
	volume = {4},
	number = {1},
	year = {2015},
	month = {2015},
	pages = {111-36},
	abstract = {The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell-cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority.},
	issn = {2076-0817},
	doi = {10.3390/pathogens4010111},
	author = {Bispo, Paulo J M and Haas, Wolfgang and Gilmore, Michael S}
}
@article {1517193,
	title = {Hospital-Associated Multidrug-Resistant MRSA Lineages Are Trophic to the Ocular Surface and Cause Severe Microbial Keratitis},
	journal = {Front Public Health},
	volume = {8},
	year = {2020},
	month = {2020},
	pages = {204},
	abstract = {Methicillin-resistant (MRSA) is a common cause of severe and difficult to treat ocular infection. In this study, the population structure of 68 ocular MRSA isolates collected at Massachusetts Eye and Ear between January 2014 and June 2016 was assessed. By using a combination of multilocus sequence typing (MLST) analysis, SCC typing and detection of the panton-valentine leukocidin (PVL) gene, we found that the population structure of ocular MRSA is composed of lineages with community and hospital origins. As determined by eBURST analysis of MLST data, the ocular MRSA population consisted of 14 different sequence types (STs) that grouped within two predominant clonal complexes: CC8 (47.0\%) and CC5 (41.2\%). Most CC8 strains were ST8, harbored type IV SCC and were positive for the PVL-toxin (93.7\%). The CC5 group was divided between strains carrying SCC type II (71.4\%) and SCC type IV (28.6\%). Remaining isolates grouped in 6 different clonal complexes with 3 isolates in CC6 and the other clonal complexes being represented by a single isolate. Interestingly, major MRSA CC5 and CC8 lineages were isolated from discrete ocular niches. Orbital and preseptal abscess/cellulitis were predominantly caused by CC8-SCC IV PVL-positive strains. In contrast, infections of the cornea, conjunctiva and lacrimal system were associated with the MDR CC5 lineage, particularly as causes of severe infectious keratitis. This niche specialization of MRSA is consistent with a model where CC8-SCC IV PVL-positive strains are better adapted to cause infections of the keratinized and soft adnexal eye tissues, whereas MDR CC5 appear to have greater ability in overcoming innate defense mechanisms of the wet epithelium of the ocular surface.},
	issn = {2296-2565},
	doi = {10.3389/fpubh.2020.00204},
	author = {Bispo, Paulo J M and Ung, Lawson and Chodosh, James and Gilmore, Michael S}
}
@article {1364584,
	title = {Decline in DJ-1 and decreased nuclear translocation of Nrf2 in Fuchs endothelial corneal dystrophy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {9},
	year = {2012},
	month = {2012 Aug 24},
	pages = {5806-13},
	abstract = {PURPOSE: This study sought to determine factors involved in nuclear factor erythroid 2-related factor 2 (Nrf2) regulation and their response to oxidative stress in Fuchs endothelial corneal dystrophy (FECD) and normal corneal endothelial cells (CECs). METHODS: FECD corneal buttons were obtained from transplantations and normal human corneas from tissue banks. Oxidative stress was induced by tert-butyl hydroperoxide (tBHP). Protein and mRNA levels of Nrf2, DJ-1, p53, and Kelch-like ECH-associated protein1 (Keap1) were investigated using Western blotting and real-time PCR. Immunoprecipitation was used to detect levels of oxidized DJ-1 protein and Cullin 3- (Cul3)-regulated degradation of DJ-1 in immortalized FECD (FECDi) and normal CEC (HCECi) cell lines. Nrf2 subcellular localization was assessed by immunocytochemistry. RESULTS: Nrf2 protein stabilizer, DJ-1, decreased significantly in FECD CECs compared with normal, whereas Nrf2 protein repressor, Keap1, was unchanged at baseline but increased under oxidative stress. Under oxidative stress, normal CECs upregulated DJ-1 protein synthesis, whereas FECD CECs did not. DJ-1 decline correlated with increased DJ-1 oxidative modification and carbonylation in FECDi as compared with HCECi. Increased labeling of immunoprecipitated DJ-1 protein with anti-Cul3 antibody indicated enhanced DJ-1 degradation in FECDi as compared with HCECi. Following tBHP treatment, Nrf2 translocated from cytoplasm to nuclei in normal CECs, whereas Nrf2 nuclear localization was not observed in FECD. CONCLUSIONS: Decreased levels of DJ-1 in FECD at baseline and under oxidative stress correlate with impaired Nrf2 nuclear translocation and heightened cell susceptibility to apoptosis. Targeting the DJ-1/Nrf2 axis could yield a mechanism to slow CEC degeneration in FECD.},
	keywords = {Aged, Blotting, Western, Cell Nucleus, Corneal Transplantation, Endothelium, Corneal, Female, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, Kelch-Like ECH-Associated Protein 1, Male, NF-E2-Related Factor 2, Oncogene Proteins, Oxidative Stress, Protein Deglycase DJ-1, Protein Transport, Real-Time Polymerase Chain Reaction, RNA, Messenger, tert-Butylhydroperoxide, Tissue Donors, Tumor Suppressor Protein p53, Up-Regulation},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-10119},
	author = {Bitar, Maya S and Liu, Cailing and Ziaei, Alireza and Chen, Yuming and Schmedt, Thore and Jurkunas, Ula V}
}
@webarticle {1460353,
	title = {Duane Syndrome},
	journal = {GeneReviews{\textregistered} [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.},
	year = {2019},
	url = {http://www.ncbi.nlm.nih.gov/books/NBK1190/},
	author = {Barry BJ and Whitman MC and Hunter DG and Engle EC}
}
@article {1664979,
	title = {Conventional type I migratory CD103+ dendritic cells are required for corneal allograft survival},
	journal = {Mucosal Immunol},
	volume = {16},
	number = {5},
	year = {2023},
	month = {2023 Oct},
	pages = {711-726},
	abstract = {Corneal transplant rejection primarily occurs because of the T helper 1 (Th1) effector cell-mediated immune response of the host towards allogeneic tissue. The evidence suggests that type 1 migratory conventional CD103+ dendritic cells (CD103+DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103+DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103+DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts. The immunosuppressive function of CD103+DC1 has been extensively studied in non-transplantation settings. We found that host CD103+DC1 infiltrates the corneal graft and migrates to the draining lymph nodes to suppress alloreactive CD4+ Th1 cells via the programmed death-ligand 1 axis. The systemic depletion of CD103+ DC1 in allograft recipients leads to amplified Th1 activation, impaired Treg function, and increased rate of allograft rejection. Although allograft recipient Rag1 null mice reconstituted with na{\"\i}ve CD4+CD25- T cells efficiently generated peripheral Treg cells (pTreg), the CD103+DC1-depleted mice failed to generate pTreg. Furthermore, adoptive transfer of pTreg failed to rescue allografts in CD103+DC1-depleted recipients from rejection. These data demonstrate the critical role of CD103+DC1 in regulating host alloimmune responses.},
	issn = {1935-3456},
	doi = {10.1016/j.mucimm.2022.12.002},
	author = {Blanco, Tomas and Singh, Rohan Bir and Nakagawa, Hayate and Taketani, Yukako and Dohlman, Thomas H and Chen, Yihe and Chauhan, Sunil K and Yin, Jia and Dana, Reza}
}
@article {1698331,
	title = {The impact of donor diabetes on corneal transplant immunity},
	journal = {Am J Transplant},
	volume = {23},
	number = {9},
	year = {2023},
	month = {2023 Sep},
	pages = {1345-1358},
	abstract = {Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80\% to 90\% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lepob/ob type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients. DM resulted in an increased frequency of corneal antigen-presenting cells (APCs) with an acquired immunostimulatory phenotype. Following transplantation, recipients that received either type of diabetic graft showed increased APC migration and T helper type 1 alloreactive cells, impaired functional regulatory T cells, and graft survival. Insulin treatment in streptozotocin-induced diabetic mice led to an increased tolerogenic profile of graft APC, lower T helper type 1 sensitization, and a higher frequency of functional regulatory T cells with high suppressive capacity, reflected in increased graft survival. We conclude that both DM1 and DM2 in donors can impact corneal APC functional phenotype, rendering the tissue more immunogenic and thereby increasing the risk of graft failure.},
	keywords = {Animals, Antigen-Presenting Cells, Cornea, Corneal Transplantation, Diabetes Mellitus, Experimental, Mice, Streptozocin},
	issn = {1600-6143},
	doi = {10.1016/j.ajt.2023.05.027},
	author = {Blanco, Tom{\'a}s and Musayeva, Aytan and Singh, Rohan Bir and Nakagawa, Hayate and Lee, Seokjoo and Alemi, Hamid and Gonzalez-Nolasco, Bruno and Ortiz, Gustavo and Wang, Shudan and Kahale, Francesca and Dohlman, Thomas H and Chen, Yihe and Dana, Reza}
}
@article {1363247,
	title = {Role of thrombospondin-1 in repair of penetrating corneal wounds},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {9},
	year = {2013},
	month = {2013 Sep 17},
	pages = {6262-8},
	abstract = {PURPOSE: Thrombospondin-1 (THBS1) has been suggested as a corneal wound-healing modulator. Therefore, we compromised the integrity of the cornea to elucidate the role of THBS1. METHODS: Full-thickness penetrating corneal incisions (1.5 mm) were created in wild type (WT, 129S2/SvPas) and THBS1-deficient mice (Thbs1$^{-}$/$^{-}$), 129S2/SvPas-Thbs1(tm1Hyn)/Thbs1(tm1Hyn)), and allowed to heal up to 1 month, while being monitored by slit-lamp and intravital corneal examinations. Corneas also were examined by transmission electron microscopy and indirect immunofluorescence. To determine how THBS1 was involved in the healing process, we examined THBS1 and α-smooth muscle actin (SMA), a marker of myofibroblasts and myoepithelial cells. RESULTS: In WT mice by 1 month, corneas appeared transparent with a thin scar, and endothelium and Descemet{\textquoteright}s membrane (DM) were restored. In contrast, Thbs1$^{-}$/$^{-}$ corneas exhibited chronic edema and persistent opacity after wounding. The DM and endothelium were not restored, and wound contraction was impaired. The THBS1 was localized in epithelial cells at early stages of the healing process, and in the stroma and endothelial cells during later stages. The SMA-positive epithelial cells and myofibroblasts were observed within the healing area at day 4, peaked at day 14, and disappeared at day 30. The SMA-positive cells were reduced greatly in Thbs1$^{-}$/$^{-}$ mice. CONCLUSIONS: In the current study, we demonstrated that corneal restoration is strikingly compromised by a penetrating incision in Thbs1$^{-}$/$^{-}$ mice. The wound results in persistent edema and wound gaping. This appears to be the result of the lack of endothelial migration and DM restoration. In addition, myofibroblast formation is compromised, resulting in the lack of wound contraction.},
	keywords = {Actins, Animals, Corneal Perforation, Corneal Stroma, Disease Models, Animal, Endothelium, Corneal, Eye Injuries, Penetrating, Female, Fluorescent Antibody Technique, Male, Mice, Mice, Knockout, Microscopy, Electron, Transmission, Myofibroblasts, Thrombospondin 1, Wound Healing},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-11710},
	author = {Blanco-Mezquita, Jos{\'e} Tom{\'a}s and Hutcheon, Audrey E K and Zieske, James D}
}
@article {1748491,
	title = {Evolution of macular atrophy in eyes with neovascular age-related macular degeneration compared to fellow non-neovascular eyes},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {261},
	number = {12},
	year = {2023},
	month = {2023 Dec},
	pages = {3425-3436},
	abstract = {PURPOSE: Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD). METHODS: This retrospective study included 124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA. RESULTS: MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study{\textquoteright}s follow-up, 45.1\% of nAMD-E developed MA, compared to 16.5\% of fellow eyes (p \&lt; 0.001). When MA in the two eyes was compared in a synchronous paired manner over 4\&nbsp;years, nAMD eyes had an average MA progression rate of 0.275\&nbsp;mm/year versus 0.110\&nbsp;mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (p \&lt; 0.001), eye (p = 0.003), and time-eye interaction (p \&lt; 0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295\&nbsp;mm/year vs. nAMD: 0.176\&nbsp;mm/year) with a significant time-eye interaction (p = 0.015). CONCLUSIONS: In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.},
	keywords = {Angiogenesis Inhibitors, Atrophy, Humans, Intravitreal Injections, Ranibizumab, Retrospective Studies, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Visual Acuity, Wet Macular Degeneration},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06168-0},
	author = {Blazaki, Styliani and Blavakis, Emmanouil and Chlouverakis, Gregory and Bontzos, Georgios and Chatziralli, Irini and Smoustopoulos, Georgios and Dimitriou, Eleni and Stavrakakis, Anastasios and Kabanarou, Stamatina and Xirou, Tina and Vavvas, Demetrios G and Tsilimbaris, Miltiadis K}
}
@article {1817251,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {131},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {e5},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.08.016},
	author = {Bleicher, Isaac D and Tainsh, Laurel T and Gaier, Eric D and Armstrong, Grayson W}
}
@article {1653582,
	title = {Acute Idiopathic Maculopathy Following SARS-CoV-2 Vaccination},
	journal = {Ocul Immunol Inflamm},
	volume = {31},
	number = {6},
	year = {2023},
	month = {2023 Aug},
	pages = {1232-1235},
	abstract = {A 49-year-old man presented with acute unilateral blurred vision one week after SARS-CoV-2 vaccination. A unilateral serous detachment of the macula, intraretinal hemorrhages, vitritis, and anterior chamber cell was found. Diagnostic testing was negative for infectious and inflammatory causes, and a diagnosis of acute idiopathic maculopathy (AIM) was made. Symptoms and serous detachment resolved over 12\&nbsp;weeks, with residual retinal pigment epithelial changes consistent with the disease course. AIM is a rare diagnosis that presented in close proximity to SARS-CoV-2 vaccination without evidence of coxsackievirus infection. Further research is necessary to clarify an association between this vaccine and uveitis.},
	keywords = {COVID-19, COVID-19 Vaccines, Fluorescein Angiography, Humans, Macular Degeneration, Male, Middle Aged, Retinal Diseases, SARS-CoV-2, Vaccination},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2114915},
	author = {Bleicher, Isaac D and Brill, Daniel and Wu, Frances and Sobrin, Lucia and Patel, Nimesh}
}
@article {1658680,
	title = {Outcomes of Zone 3 Open Globe Injuries by Wound Extent: Subcategorization of Zone 3 Injuries Segregates Visual and Anatomic Outcomes},
	journal = {Ophthalmology},
	volume = {130},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {379-386},
	abstract = {PURPOSE: Open globe injuries (OGIs) are categorized by zone, with zone 3 (Z3) comprising wounds \&gt; 5 mm beyond the limbus. Outcomes of Z3 OGIs are highly heterogeneous. Open globe injuries with far posterior Z3 (pZ3) wounds were hypothesized to have worse visual and anatomic outcomes. DESIGN: Single-center retrospective cohort study. PARTICIPANTS: A total of 258 eyes with Z3 OGIs. METHODS: A retrospective review of Z3 OGIs treated at a tertiary center over 12 years. Wounds >= 10 mm posterior to the limbus were defined as pZ3. Outcomes were compared between pZ3 and anterior Z3 (aZ3) eyes. MAIN OUTCOME MEASURES: Visual acuity on a logarithm of the minimum angle of resolution (logMAR) scale. Secondary outcomes included anatomic outcomes, development of retinal detachment and proliferative vitreoretinopathy, and the number of secondary surgeries. RESULTS: A total of 258 Z3 OGI eyes with \&gt; 30 days follow-up were assessed; 161 (62\%) were pZ3. At 3-month follow-up, pZ3 OGIs were more likely to exhibit no light perception (pZ3: 38\%; aZ3: 17\%; P \&lt; 0.003), lack count fingers vision (pZ3: 72\%; aZ3: 43\%; P \&lt; 0.002), and fail to read a letter on the eye chart (pZ3: 83\%; aZ3: 64\%; P \&lt; 0.001). The visual acuity distribution at 3 months was significantly worse for pZ3 compared with aZ3 injuries (P \&lt; 0.004). Similar results were found at final follow-up. Multiple linear regression showed that pZ3 location was independently associated with worse visual acuity (β\&nbsp;= 0.29, 95\% confidence interval [CI], 0.09-0.50, P \&lt; 0.006) in addition to presenting acuity, age, vitreous hemorrhage, uveal prolapse, and afferent pupillary defect. Far posterior wounds injuries were more likely to develop retinal detachments (pZ3: 87\%; aZ3: 71\%; P \&lt; 0.01) and proliferative vitreoretinopathy (pZ3 66\%; aZ3 47\%; P \&lt; 0.03). Patients with pZ3 OGIs were significantly more likely to reach poor anatomic outcome (phthisis, enucleation, need for keratoprosthesis) compared with patients with aZ3 OGI (pZ3: 56\%; aZ3: 40\%; P \&lt; 0.03). CONCLUSIONS: Posterior OGI extension independently portends worse visual and anatomic outcomes. The effect on visual outcome was durable and clinically relevant compared with established predictors of OGI outcomes. Application of these findings improves the prognostic precision and will guide future research efforts to optimize surgical decision-making in severe OGI cases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Cornea, Corneal Diseases, Eye Injuries, Eye Injuries, Penetrating, Humans, Prognosis, Prostheses and Implants, Retinal Detachment, Retrospective Studies, Vitreoretinopathy, Proliferative},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.10.027},
	author = {Bleicher, Isaac D and Tainsh, Laurel T and Gaier, Eric D and Armstrong, Grayson W}
}
@article {1642032,
	title = {Reevaluating the Risk of Serious Adverse Events of Carbonic Anhydrase Inhibitors},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {7},
	year = {2022},
	month = {2022 Jul 01},
	pages = {745-746},
	keywords = {Carbonic Anhydrase Inhibitors, Humans},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.1565},
	author = {Bleicher, Isaac D and Rossin, Elizabeth J and Vavvas, Demetrios G}
}
@article {1817286,
	title = {WIDEFIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN WAGNER SYNDROME},
	journal = {Retin Cases Brief Rep},
	volume = {18},
	number = {1},
	year = {2024},
	month = {2024 Jan 01},
	pages = {80-86},
	abstract = {PURPOSE: To describe novel clinical and angiographic findings in Wagner syndrome.

METHODS: A retrospective case series of three related patients with Wagner syndrome. Patients underwent standard optical coherence tomography (OCT), B-scan ultrasonography, and fluorescein angiography in addition to wide field swept-source OCT angiography (WF SS-OCTA) (PLEX Elite 9000, Carl Zeiss Meditec Inc). Patients underwent genetic testing for a panel of hereditary vitreoretinopathies.

RESULTS: Three related patients with Wagner syndrome were identified. All were found to have prominent vitreous strands, abnormal vitreoretinal adhesions, peripheral retinal holes, and varying degrees of myopia. A mid-peripheral tractional ridge was identified in all six eyes. All patients were positive for a known pathologic intron variant in the VCAN gene (4004-5T-A). Wide field swept-source OCT angiography (12 mm {\texttimes} 12 mm) was performed in two patients and demonstrated perivascular capillary loss in the superficial capillary plexus along the arcades bilaterally. One patient demonstrated associated retinal atrophy within the area of capillary loss. The capillary loss extended beyond the margin of retinal atrophy.

CONCLUSION: The unusual finding of a mid-peripheral tractional ridge of the retina associated with myopia led to a genetic diagnosis of Wagner syndrome. Widefield swept-source OCT angiography demonstrated a novel feature of perivascular loss of the superficial retinal capillary plexus. This result suggests that vitreous traction may cause localized microvasculature dysfunction and subsequent retinal atrophy in Wagner syndrome. This is the first known evaluation of Wagner syndrome using OCT angiography.},
	keywords = {Atrophy, Fluorescein Angiography, Humans, Myopia, Retinal Degeneration, Retinal Vessels, Retrospective Studies, Tomography, Optical Coherence},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001307},
	author = {Bleicher, Isaac D and Garg, Itika and Hoyek, Sandra and Place, Emily and Miller, John B and Patel, Nimesh A}
}
@article {1814381,
	title = {Giant Retinal Tears: A Review With a Focus on Trauma},
	journal = {Int Ophthalmol Clin},
	volume = {64},
	number = {2},
	year = {2024},
	month = {2024 Apr 01},
	pages = {107-123},
	keywords = {Humans, Retinal Detachment, Retinal Perforations, Visual Acuity, Vitrectomy},
	issn = {1536-9617},
	doi = {10.1097/IIO.0000000000000491},
	author = {Bleicher, Isaac and Miller, John B}
}
@article {1651364,
	title = {Widefield Swept-Source Optical Coherence Tomography Angiography Findings in Wagner Syndrome},
	journal = {Retin Cases Brief Rep},
	year = {2022},
	author = {Bleicher, ID and Garg, I and Hoyek, S and Place, E and Miller, JB and Patel, NA}
}
@article {603881,
	title = {Endoscopic endonasal orbital cavernous hemangioma resection: global experience in techniques and outcomes.},
	journal = {Int Forum Allergy Rhinol},
	year = {2015},
	month = {2015 Dec 1},
	abstract = {BACKGROUND: Endoscopic orbital surgery represents the next frontier in endonasal surgery. The current literature is largely composed of small, heterogeneous, case series with little consensus regarding optimal techniques. The purpose of this study was to combine the experience of multiple international centers to create a composite of the global experience on the endoscopic management of a single type of tumor, the orbital cavernous hemangioma (OCH). METHODS: This was a retrospective study of techniques for endoscopic OCH resection from 6 centers on 3 continents. Only primary data from strictly endoscopic resection of OCHs were included. Responses were analyzed to qualitatively identify points of both consensus and variability among the different groups. RESULTS: Data for a total of 23 patients, 10 (43.5\%) male and 13 (56.5\%) female were collected. The majority of lesions were intraconal (60.9\%). The mean {\textpm} standard deviation (SD) surgical time was 150.7 {\textpm} 75.0 minutes with a mean blood loss of 82.7 {\textpm} 49.6 mL. Binarial approaches (26.1\%) were used exclusively in the setting of intraconal lesions, which were associated with a higher rate of incomplete resection (31.3\%), postoperative diplopia (25.0\%), and the need for reconstruction (37.5\%) than extraconal lesions. Orthotropia and symmetric orbital appearance were achieved in 60.9\% and 78.3\% of cases, respectively. CONCLUSION: Extraconal lesions were managed similarly; however, greater variability was evident for intraconal lesions. These included the laterality and number of hands in the approach, methods of medial rectus retraction, and the need for reconstruction. The increased technical complexity and disparity of techniques in addressing intraconal OCHs suggests that continued research into the optimal management of this subclass of lesions is of significant priority.},
	issn = {2042-6984},
	doi = {10.1002/alr.21645},
	author = {Bleier, Benjamin S and Castelnuovo, Paolo and Battaglia, Paolo and Turri-Zanoni, Mario and Dallan, Iacopo and Metson, Ralph and Sedaghat, Ahmad R and Stefko, S Tonya and Gardner, Paul A and Snyderman, Carl H and Nogueira, Joao Flavio and Ramakrishnan, Vijay R and Muscatello, Luca and Lenzi, Riccardo and Freitag, Suzanne}
}
@article {313231,
	title = {Compartmental endoscopic surgical anatomy of the medial intraconal orbital space.},
	journal = {Int Forum Allergy Rhinol},
	volume = {4},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {587-91},
	abstract = {BACKGROUND: Surgical management of intraconal pathology represents the next frontier in endoscopic endonasal surgery. Despite this, the medial intraconal space remains a relatively unexplored region, secondary to its variable and technically demanding anatomy. The purpose of this study is to define the neurovascular structures in this region and introduce a compartmentalized approach to enhance surgical planning. METHODS: This study was an institutional review board (IRB)-exempt endoscopic anatomic study in 10 cadaveric orbits. After dissection of the medial intraconal space, the pattern and trajectory of the oculomotor nerve and ophthalmic arterial arborizations were analyzed. The position of all vessels as well as the length of the oculomotor trunk and branches relative to the sphenoid face were calculated. RESULTS: A mean of 1.5 arterial branches were identified (n = 15; range, 1-4) at a mean of 8.8 mm from the sphenoid face (range, 4-15 mm). The majority of the arteries (n = 7) inserted adjacent to the midline of medial rectus. The oculomotor nerve inserted at the level of the sphenoid face and arborized with a large proximal trunk 5.5 {\textpm} 1.1 mm in length and multiple branches extending 13.2 {\textpm} 2.7 mm from the sphenoid face. The most anterior nerve and vascular pedicle were identified at 17.0 and 15.0 mm from the sphenoid face, respectively. CONCLUSION: The neurovascular supply to the medial rectus muscle describes a varied but predictable pattern. This data allows the compartmentalization of the medial intraconal space into 3 zones relative to the neurovascular supply. These zones inform the complexity of the dissection and provide a guideline for safe medial rectus retraction relative to the fixed landmark of the sphenoid face.},
	issn = {2042-6984},
	doi = {10.1002/alr.21320},
	author = {Bleier, Benjamin S and Healy, David Y and Chhabra, Nipun and Freitag, Suzanne}
}
@article {1773601,
	title = {Home Optical Coherence Tomography Imaging for Newly Diagnosed Neovascular Age-Related Macular Degeneration: A Feasibility Study},
	journal = {Ophthalmol Retina},
	year = {2023},
	month = {2023 Oct 23},
	abstract = {OBJECTIVE: To assess the feasibility of daily home optical coherence tomography (OCT) imaging among patients with neovascular age-related macular degeneration (nAMD). DESIGN: Prospective observational study. PARTICIPANTS: Participants with at least one eye with previously untreated nAMD and visual acuity 20/20 to 20/320. METHODS: Participants meeting the ocular eligibility criteria were considered for enrollment; those who provided consent received a Notal Vision Home OCT device. Participants were instructed to scan both eyes daily. Retina specialists managed treatment according to their standard practice, without access to the Home OCT data. The presence of fluid detected by a reading center from in-office OCT scans was compared to fluid volumes measured by the Notal OCT Analyzer (NOA) on Home OCT images. MAIN OUTCOME MEASURES: Proportion of participants meeting ocular eligibility criteria who participated in daily scanning, frequency and duration of scanning, proportion of scans eligible for fluid quantification, participant experience with the device, agreement between the reading center and NOA fluid determinations, and characteristics of fluid dynamics. RESULTS: Among 40 participants meeting ocular eligibility criteria, 14 (35\%) initiated self-scanning. Planned travel (n=7, 17.5\%) and patient-reported inadequate cell reception for the upload of images (n=5, 12.5\%) were the most frequent reasons for not participating. Considering scans of the study eye only, the mean (SD) was 6.3 (0.6) for weekly scanning frequency and 47 (17) seconds for scan duration per eye. Among 2,304 scans, 86.5\% were eligible for fluid quantification. All participants agreed that scanning became easier over time, and only one would not want to continue daily scanning. For 35 scan pairs judged as having fluid by in-office OCT, the NOA detected fluid on 31 scans (89\%). For 14 scan pairs judged as having no fluid on in-office OCT, the NOA did not detect fluid on 10 scans (71\%). Daily fluid patterns after treatment initiation varied considerably between patients. CONCLUSIONS: For patients with nAMD who initiated home scanning, frequency and quality of scanning and accuracy of fluid detection were sufficient to assess the monitoring of fluid at home. Accommodations for travel and Wi-Fi connectivity could improve uptake of the Home OCT device.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.10.012},
	author = {Blinder, Kevin J and Calhoun, Claire and Maguire, Maureen G and Glassman, Adam R and Mein, Calvin E and Baskin, Darrell E and Vieyra, Gabriela and Jampol, Lee M and Chica, Moises A and Sun, Jennifer K and Martin, Daniel F and DRCR Retina Network}
}
@article {1642013,
	title = {Ocular complications with the use of radium-223: a case series},
	journal = {Radiat Oncol},
	volume = {17},
	number = {1},
	year = {2022},
	month = {2022 May 17},
	pages = {97},
	abstract = {BACKGROUND: Radium-223 is used for the treatment of osseous metastases in castrate-resistant prostate cancer, and has been shown to increase time to the first skeletal-related event, reduce the rate of hospitalization, and improve quality of life. It is well tolerated, with hematologic toxicity as the main adverse event. Thus far, no ocular complication has been reported in the literature after initial administration of radium-223 with a single case reported of ocular complications after a patient{\textquoteright}s second course of radium-223. CASE PRESENTATIONS: We present three cases of ocular complications after the use of radium-223 in patients with metastatic prostatic adenocarcinoma. Ocular complications presented as blurry vision, and formal diagnosis included uveitis and hyphema. CONCLUSIONS: Documentation of adverse events is exceedingly important due to the high incidence of metastatic prostate cancer and increasing interest for the use of radium-223 in other osteoblastic disease. The authors postulate that these ocular complications may be a result of radiation{\textquoteright}s potential effect on neovascularization, polypharmacy, or the biomolecular effects of radium-223 on integral signaling proteins, potentially coupled with poor underlying ocular health.},
	keywords = {Bone Neoplasms, Humans, Male, Prostatic Neoplasms, Castration-Resistant, Quality of Life, Radium},
	issn = {1748-717X},
	doi = {10.1186/s13014-022-02060-z},
	author = {Bloom, Julie R and Castillejos, Alexandra G and Jones, Brianna and Patel, Nimesh and Rosenstein, Barry S and Stock, Richard G}
}
@article {1732576,
	title = {Antibiotic utilization in endoscopic dacryocystorhinostomy: a multi-institutional study and review of the literature},
	journal = {Orbit},
	year = {2023},
	month = {2023 Jul 03},
	pages = {1-7},
	abstract = {PURPOSE: Utilization of antibiotics for endoscopic dacryocystorhinostomy (endo-DCR) is largely dependent on individual surgeon preference. This study aimed to investigate prescribing practices of pre-, peri-, and postoperative antibiotics and effects on postoperative infection rates in patients who underwent endo-DCR. METHODS: A retrospective chart review of institutional data at two academic centers of endo-DCR cases from 2015-2020 was performed. Postoperative infection rates for patients who received pre-, peri-, and postoperative antibiotics, individually or in combination, and those who did not, were compared via odds ratio and ANOVA linear regression. RESULTS: 331 endo-DCR cases were included; 22 cases (6.6\%) had a postoperative infection. There was no significant difference in the infection rates between patients without an active preoperative dacryocystitis who received different permutations of peri- and postoperative antibiotics. Patients who received preoperative antibiotics within two weeks of surgery for preexisting acute dacryocystitis, but did not receive peri- or postoperative antibiotics, had a higher rate of postoperative infections (p = 008). CONCLUSIONS: Our data suggest antibiotics may be beneficial only when patients have a recent or active dacryocystitis prior to surgery. Otherwise, our data do not support the routine use of antibiotic prophylaxis in endo-DCR.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2023.2227705},
	author = {Boal, Nina S and Chiou, Carolina A and Sadlak, Natalie and Sarmiento, V Adrian and Lefebvre, Daniel R and Distefano, Alberto G}
}
@article {1598066,
	title = {In vivo analysis of endocanalicular light pipe transillumination in endoscopic dacryocystorhinostomy: Anatomic considerations and cautions for the transitioning},
	journal = {Orbit},
	year = {2021},
	month = {2021 Jun 03},
	pages = {1-5},
	abstract = {Purpose: Localization of the lacrimal sac is a critical step during endoscopic dacryocystorhinostomy (endo-DCR). A "light pipe" can be used to transilluminate the lacrimal sac endonasally. We hypothesized that this may misguide the surgeon learning endo-DCR to create an osteotomy mostly posterior to the maxillary line if only the bone overlying the transillumination was to be removed, as the thinner lacrimal bone will transmit light more readily than the thicker maxillary bone of the frontal process of the maxilla that forms the anterior lacrimal sac fossa.Methods: The charts of 32 patients with primary acquired nasolacrimal duct obstruction in whom a lighted system was used during endo-DCR at Massachusetts Eye and Ear from April 2015 through October 2016 were reviewed. Patients with prior history of lacrimal surgery or trauma directly to the lacrimal sac fossa were excluded. Location of the maximal point of transillumination in relation to the maxillary line was observed and noted intraoperatively.Results: Of a total of 39 endo-DCR surgeries performed, the intraoperative transillumination point was entirely posterior to the maxillary line in 32 instances (82\%).Conclusions: Use of an endocanalicular light pipe preferentially illuminates posterior to the maxillary line endonasally. The anterior lacrimal sac fossa (maxillary line and anterior as visualized endonasally) is rarely transilluminated, likely due to thicker bone in that region. Surgeons learning how to perform endo-DCR using a light pipe should be aware of this phenomenon.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2021.1929340},
	author = {Boal, Nina S and Cretara, Elizabeth A Z and Bleier, Benjamin S and Lam, Allen C and Lefebvre, Daniel R}
}
@article {1359925,
	title = {Vitamin D and omega-3 trial to prevent and treat diabetic kidney disease: Rationale, design, and baseline characteristics},
	journal = {Contemp Clin Trials},
	volume = {74},
	year = {2018},
	month = {2018 Nov},
	pages = {11-17},
	abstract = {Diabetic kidney disease (DKD), defined as reduced glomerular filtration rate (GFR), elevated urine albumin excretion, or both that is clinically attributable to diabetes, is a common and morbid diabetes complication. Animal-experimental data, observational human studies, and short-term clinical trials suggest that vitamin D and omega-3 fatty acid supplements may be safe and inexpensive interventions to reduce the incidence and progression of DKD. The Vitamin D and Omega-3 Trial to Prevent and Treat DKD (VITAL-DKD) was designed as an ancillary study to the VITAL trial of 25,871 US adults. In a 2 {\texttimes} 2 factorial design, VITAL participants were randomly assigned to vitamin D (cholecalciferol, 2000 IU daily) or placebo and to marine omega-3 fatty acids (eicospentaenoic acid and docosahexaenoic acid, 1 g/d) or placebo. VITAL-DKD enrolled a subset of 1326 VITAL participants with type 2 diabetes at baseline to test the effects of vitamin D and omega-3 fatty acids on changes in estimated GFR and urine albumin excretion. Over five years of follow-up, VITAL-DKD collected blood and urine samples to quantify changes in estimated GFR (the primary study outcome) and urine albumin excretion. At baseline, mean age of VITAL-DKD participants was 67.6 years, 46\% were women, 30\% were of racial or ethnic minority, and the prevalence of DKD (estimated GFR \&lt;60 mL/min/1.73m or urine albumin-creatinine ratio >= 30 mg/g) was 17\%. In this type 2 diabetes population, VITAL-DKD will test the hypotheses that vitamin D and omega-3 fatty acids help prevent the development and progression of DKD.},
	issn = {1559-2030},
	doi = {10.1016/j.cct.2018.09.014},
	author = {de Boer, Ian H and Zelnick, Leila R and Lin, Julie and Schaumberg, Debra and Wang, Lu and Ruzinski, John and Friedenberg, Georgina and Duszlak, Julie and Bubes, Vadim Y and Hoofnagle, Andrew N and Thadhani, Ravi and Glynn, Robert J and Buring, Julie E and Sesso, Howard D and Manson, JoAnn E}
}
@article {1615208,
	title = {Intraoperative OCT versus Scheimpflug and Swept-Source OCT measurements for anterior eye parameters},
	journal = {J Cataract Refract Surg},
	year = {2021},
	month = {2021 Sep 01},
	abstract = {PURPOSE: To compare agreement of anterior segment parameter measurements using an intraoperative optical coherence tomography (iOCT) of a femtosecond laser (LenSx) during interface docking to the eye to preoperative Scheimpflug-tomography (Pentacam AXL) and swept-source optical coherence tomography (IOL Master 700). SETTING: Department of Ophthalmology, Goethe University, Frankfurt, Germany. DESIGN: Retrospective study. METHODS: Ninty-five eyes of 66 patients who had planned OCT-guided femtosecond laser-assisted lens surgery were included. Anterior segment measurements were performed in mydriasis prior to surgery using Scheimpflug-tomography and swept-source optical coherence tomography. After surgery iOCT images were analysed using a modification of the FIJI image processing program. Outcome measures included external anterior chamber depth (ACD), central corneal thickness (CCT) and central lens thickness (LT). RESULTS: The ACD measured with the iOCT was -0.011{\textpm}0.126mm smaller (p=0.389) than with theswept-source OCT and -0.059{\textpm}0.185mm than with the Scheimpflug-tomography (p=0.003). The swept-source OCT measures a -0.047{\textpm}0.146mm smaller ACD than the Scheimpflug-tomography (p=0.002). The measurements of CCT using the iOCT and the Scheimpflug-tomography (-0.705{\textpm}20.837μm, p=0.742) and the LT measurements of swept-source OCT and iOCT (-0.050{\textpm}0.089mm, p\&lt;0.001) show no clinically relevant difference. Just the ACD between the iOCT and the Scheimpflug-tomography shows a clinically relevant difference. CONCLUSION: The comparison of the anterior segment parameters of intraoperative optical coherence tomography with swept-source optical coherence tomography showed no clinically relevant differences regarding the ACD and the lens thickness. However, Scheimpflug-tomography versus intraoperative optical coherence tomography measures a small clinically relevant difference for ACD.},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000000813},
	author = {B{\"o}hm, Myriam and M{\"u}ller, Michael and Paul, Julia and Hemkeppler, Eva and Kohnen, Thomas}
}
@article {1580495,
	title = {Cost-effectiveness analysis of preloaded versus non-preloaded Descemet membrane endothelial keratoplasty for the treatment of Fuchs endothelial corneal dystrophy in an academic centre},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {7},
	year = {2022},
	month = {2022 07},
	pages = {914-922},
	abstract = {AIMS: To determine the cost-effectiveness of preloaded Descemet membrane endothelial keratoplasty (pDMEK) versus non-preloaded DMEK (n-pDMEK) for the treatment of Fuchs endothelial corneal dystrophy (FECD). METHODS: From a societal and healthcare perspective, this retrospective cost-effectiveness analysis analysed a cohort of 58 patients with FECD receiving pDMEK (n=38) or n-pDMEK (n=30) from 2016 to 2018 in the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA. Exclusion criteria were previous ocular surgeries (other than uncomplicated cataract surgery), including other keratoplasty procedures, ocular pathological conditions as glaucoma, amblyopia, laser treatments, or any retinal or corneal disease. The main outcome parameters were the incremental cost-utility ratio (ICUR) and net monetary benefit (NMB). RESULTS: pDMEK was less costly compared with n-pDMEK (healthcare: $13 886 vs $15 329; societal: $20 805 vs $22 262), with a slighter greater utility (QALY 0.6682 vs QALY 0.6640) over a time horizon of 15 years. pDMEK offered a slightly higher clinical effectiveness (+0.0042 QALY/patient) at a lower cost (healthcare: -$1444 per patient; societal: -$1457 per patient) in improving visual acuity in this cohort of patients with FECD. pDMEK achieved a favourable ICUR and NMB compared with n-pDMEK. Based on sensitivity analyses performed, the economic model was robust. CONCLUSIONS: From the societal and healthcare perspective, pDMEK was less costly and generated comparable utility values relative to n-pDMEK. Therefore, pDMEK appears to be cost-effective and cost saving with respect to n-pDMEK. Further long-term follow-up data are needed to confirm these findings.},
	keywords = {Cost-Benefit Analysis, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-317536},
	author = {B{\"o}hm, Myriam and Leon, Pia and Wyl{\k e}ga{\l}a, Adam and Ong Tone, Stephan and Condron, Tracy and Jurkunas, Ula}
}
@article {1586149,
	title = {One-Year Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty Versus Non-Preloaded Descemet Membrane Endothelial Keratoplasty},
	journal = {Cornea},
	volume = {40},
	number = {3},
	year = {2021},
	month = {2021 Mar 01},
	pages = {311-319},
	abstract = {PURPOSE: To compare the one-year outcomes of preloaded Descemet membrane endothelial keratoplasty (pDMEK) and non-preloaded DMEK (n-pDMEK) in patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: This retrospective comparative cohort study consecutively included 68 eyes with Fuchs endothelial corneal dystrophy who underwent either pDMEK (n = 38) or n-pDMEK (n = 30) performed by cornea fellows with an experienced surgeon between 2016 and 2018 at the Massachusetts Eye and Ear Infirmary. Exclusion criteria were previous surgery (other than uncomplicated cataract surgery) and any documented evidence of macular or other corneal diseases. Corrected distance visual acuity (CDVA), central corneal thickness, intraocular pressure, patient characteristics, postprocessing endothelial cell count, donor graft data, and complications were compared. RESULTS: CDVA showed similar results for pDMEK (0.12 {\textpm} 0.11 logarithm of the minimal angle of resolution [LogMAR]) and n-pDMEK (0.13 {\textpm} 0.13 LogMAR) (P = 0.827). Sixty-six percent of the pDMEK eyes and 57\% of the n-pDMEK eyes achieved a VA of >=0.1 LogMAR, and 95\% and 97\%, respectively, achieved a CDVA >=0.3 LogMAR. The preoperative central corneal thickness of pDMEK and n-pDMEK (644 {\textpm} 62.2 μm, 660.5 {\textpm} 56.2 μm) decreased significantly after surgery (525.1 {\textpm} 43.6 μm, 526.5 {\textpm} 45.2 μm, P \&lt; 0.001), with no difference between groups (P = 0.840). The postprocessing endothelial cell count did not differ between pDMEK (2959.2 {\textpm} 182.9 cells/mm2) and n-pDMEK (2939.3 {\textpm} 278.7 cells/mm2) (P = 0.484). Complication rates were comparable with just the rebubbling performed in a minor procedure room showing a lower rate for pDMEK (13.16\%) compared with n-pDMEK (33.33\%) (P \&lt; 0.045). CONCLUSIONS: One-year clinical outcomes were similar between pDMEK and n-pDMEK procedures, rendering eye bank-prepared pDMEK tissues a useful tool in the treatment of endothelial dysfunction.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002430},
	author = {B{\"o}hm, Myriam S and Wylegala, Adam and Leon, Pia and Ong Tone, Stephan and Ciolino, Joseph B and Jurkunas, Ula V}
}
@article {1474213,
	title = {Defocus curves of 4 presbyopia-correcting IOL designs: Diffractive panfocal, diffractive trifocal, segmental refractive, and extended-depth-of-focus},
	journal = {J Cataract Refract Surg},
	volume = {45},
	number = {11},
	year = {2019},
	month = {2019 Nov},
	pages = {1625-1636},
	abstract = {PURPOSE: To evaluate the defocus curves of 4 presbyopia-correcting intraocular lenses (IOLs). SETTING: Department of Ophthalmology, Goethe University, Frankfurt, Germany. DESIGN: Prospective case series. METHODS: Patients included in the study had bilateral surgery with implantation of diffractive panfocal, diffractive trifocal, segmental refractive (SegRef), or extended-depth-of-focus (EDOF) presbyopia-correcting IOLs. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, uncorrected intermediate and near visual acuities, distance-corrected intermediate (DCIVA) and near (DCNVA) visual acuities, defocus curve, and spectacle independence were measured. RESULTS: The UDVA and CDVA were not significantly different between groups (P\&nbsp;\&gt;\&nbsp;.05); however, the EDOF group had worse near CDVA (P\&nbsp;\&lt;\&nbsp;.001). The trifocal and EDOF groups showed better DCIVA\&nbsp;than the panfocal and SegRef group at 80\&nbsp;cm\&nbsp;(P\&nbsp;\&lt;\&nbsp;.001); the EDOF and panfocal groups had comparable DCIVA at 60\&nbsp;cm\&nbsp;(P\&nbsp;\&gt;\&nbsp;.05). Defocus curves showed no significant between-group differences from 4\&nbsp;m to 2\&nbsp;m\&nbsp;(P\&nbsp;\&gt;\&nbsp;.05). The EDOF group had better visual acuity from 1\&nbsp;m to 67\&nbsp;cm than the trifocal and SegRef groups and better visual acuity than the panfocal group at 1\&nbsp;m\&nbsp;(P\&nbsp;\&gt;\&nbsp;.05). Compared with the other IOLs, the panfocal IOL yielded significantly better visual acuity at 50\&nbsp;cm\&nbsp;(P\&nbsp;\&lt;\&nbsp;.001) and the EDOF IOL worse visual acuity at 40\&nbsp;cm\&nbsp;(P\&nbsp;\&lt;\&nbsp;.01). There was a significant difference in spectacle independence between the panfocal group and EDOF group (P\&nbsp;\&lt;\&nbsp;.05) but no difference between the other groups. CONCLUSIONS: The 4 IOLs provided equally good CDVA. The EDOF IOL yielded slightly better DCIVA but worse DCNVA than the other IOLs. Only the panfocal IOL gave better DCIVA at 50\&nbsp;cm.},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2019.07.014},
	author = {B{\"o}hm, Myriam and Petermann, Kerstin and Hemkeppler, Eva and Kohnen, Thomas}
}
@article {1615228,
	title = {Changes in Performance of Glaucoma Surgeries 1994 through 2017 Based on Claims and Payment Data for United States Medicare Beneficiaries},
	journal = {Ophthalmol Glaucoma},
	volume = {4},
	number = {5},
	year = {2021},
	month = {2021 Sep-Oct},
	pages = {463-471},
	abstract = {PURPOSE: To evaluate trends in glaucoma procedures in the United States Medicare population and to evaluate which physicians are performing newer procedures. DESIGN: Analysis of publicly available claims and payment data. PARTICIPANTS: Surgeons and beneficiaries enrolled in United States Medicare between 1994 and\&nbsp;2017. METHODS: Data regarding payments to physicians by the Centers for Medicare and Medicaid Services (CMS) were downloaded for the years 2012 through 2017. Data regarding claims to CMS by physicians were requested and processed between 1994 and 2017. Procedure counts from both data sets then were normalized for changes in the Medicare population, with 1995 as the baseline. The normalized volumes of procedures over time were visualized, as were geographic distributions of surgeons and their volume of procedures. MAIN OUTCOME MEASURES: Trends in procedure counts over time, geographic distribution of surgeons, and their volume of procedures. RESULTS: The number of trabeculectomies continues to decline and now is similar to the number of tubes. Use of the relatively new trabecular bypass shunts has increased rapidly. Surgeons performing these procedures are less likely to be performing traditional glaucoma surgeries as well. The number of laser-based cyclodestruction procedures increased after introduction of the endoscopic technique and again with the introduction of so-called micropulse procedures. The procedure counts obtained with physician payment data consistently are lower than those from claims data given the limitations of the payment data. CONCLUSIONS: Glaucoma practice patterns change each time a new device or procedure is introduced. Collectively, the use of new microinvasive glaucoma surgery procedures has increased rapidly such that they now account for a significant majority of glaucoma surgeries. Given the almost complete lack of comparative data to inform surgeon choices regarding these procedures, it will be important that randomized studies are carried out to fill this gap.},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.01.004},
	author = {Boland, Michael V and Corcoran, Kevin J and Lee, Aaron Y}
}
@article {1817281,
	title = {Classification and Growth Rate of Chorioretinal Atrophy after Voretigene Neparvovec-Rzyl for RPE65-Mediated Retinal Degeneration},
	journal = {Ophthalmol Retina},
	volume = {8},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {42-48},
	abstract = {PURPOSE: Classify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration.

DESIGN: Multicenter retrospective analysis.

SUBJECTS: Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior-pole chorioretinal atrophy.

METHODS: Ultrawidefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with >= 2 of the following: (1) partial or complete retinal pigment epithelial depigmentation; (2) round shape; (3) sharp margins; and (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed-effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area.

MAIN OUTCOME MEASURES: Number of eyes with each atrophy pattern, and slopes of linear mixed-effects models.

RESULTS: Twenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 {\textpm} 2.7 images per eye obtained over 2.2 {\textpm} 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated \&gt; 1 type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed-effects models of atrophy area and square root of atrophy area (estimate {\textpm} standard error) were 1.7 {\textpm} 1.3 mm2/year and 0.6 {\textpm} 0.2 mm/year for touchdown atrophy, 5.5 {\textpm} 1.3 mm2/year and 1.2 {\textpm} 0.2 mm/year for nummular atrophy, and 16.7 {\textpm} 1.8 mm2/year and 2.3 {\textpm} 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (P \&lt; 0.05).

CONCLUSIONS: Chorioretinal atrophy after subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly, while touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Atrophy, Choroid Diseases, Humans, Retinal Degeneration, Retrospective Studies},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.08.017},
	author = {Bommakanti, Nikhil and Young, Benjamin K and Sisk, Robert A and Berrocal, Audina M and Duncan, Jacque L and Bakall, Benjamin and Mathias, Marc T and Ahmed, Ishrat and Chorfi, Sarah and Comander, Jason and Nagiel, Aaron and Besirli, Cagri G}
}
@article {1347427,
	title = {Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations},
	journal = {Hum Genet},
	volume = {137},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {847-862},
	abstract = {Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95\% CI 1.26-1.93; P = 4.79 {\texttimes} 10). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR 0.48; P = 3.75 {\texttimes} 10), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.},
	keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Female, Genetic Loci, Genome-Wide Association Study, Glaucoma, Open-Angle, Humans, Male, Middle Aged, Thioredoxin Reductase 2, Vesicular Transport Proteins},
	issn = {1432-1203},
	doi = {10.1007/s00439-018-1943-7},
	author = {Bonnemaijer, Pieter W M and Iglesias, Adriana I and Nadkarni, Girish N and Sanyiwa, Anna J and Hassan, Hassan G and Cook, Colin and GIGA Study Group and Simcoe, Mark and Taylor, Kent D and Schurmann, Claudia and Belbin, Gillian M and Kenny, Eimear E and Bottinger, Erwin P and van de Laar, Suzanne and Wiliams, Susan E I and Akafo, Stephen K and Ashaye, Adeyinka O and Zangwill, Linda M and Girkin, Christopher A and Ng, Maggie C Y and Rotter, Jerome I and Weinreb, Robert N and Li, Zheng and Allingham, R Rand and Eyes of Africa Genetics Consortium and Nag, Abhishek and Hysi, Pirro G and Meester-Smoor, Magda A and Wiggs, Janey L and NEIGHBORHOOD Consortium and Hauser, Michael A and Hammond, Christopher J and Lemij, Hans G and Loos, Ruth J F and van Duijn, Cornelia M and Thiadens, Alberta A H J and Klaver, Caroline C W}
}
@article {1559544,
	title = {Nonresponders to Ranibizumab Anti-VEGF Treatment Are Actually Short-term Responders: A Prospective Spectral-Domain OCT Study},
	journal = {Ophthalmol Retina},
	volume = {4},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {1138-1145},
	abstract = {PURPOSE: To investigate the inter-individual variability in duration of anti-vascular endothelial growth factor (VEGF) treatment effect in neovascular age-related macular degeneration (nvAMD). DESIGN: Prospective observational multi-centered study. PARTICIPANTS: Forty-eight patients with nvAMD treated with anti-VEGF injections were included. Both treatment naive (n=25) as well as patients who had previously received treatment with ranibizumab (n=23) more than one month prior to their enrollment were recruited. METHODS: Patients received injection with ranibizumab (0.5 mg/0.05 ml) and were followed weekly for 4 weeks with spectral-domain OCT (SD-OCT) assessing the time to maximal reduction of central retinal thickness (CRT) and the presence of intraretinal and subretinal fluid. Other data collected included age, gender, visual acuity, axial length, lens status, and previous injections. The Shapiro-Wilk test was used to examine normal distributions for all variables. Correlations were examined by calculating Spearman{\textquoteright}s correlation coeficient. Distributions of quantitative variables are described as means ({\textpm}SD). Qualitative variables are summarized by counts and percentage. MAIN OUTCOME MEASURES: Time to maximal reduction of CRT and intra- and subretinal fluid after ranibizumab injection. RESULTS: A total of 48 eyes of 48 patients (age 74.8{\textpm}8.3 years, 62.5\% female, 52\% treatment naive, 35.4\% pseudophakic) were assessed. Two-thirds (64.6\%) reached maximal CRT reduction earlier than the standard 4-week interval: 6.3\% at 1 week postinjection, 22.9\% at 2 weeks postinjection, and 35.4\% at 3 weeks postinjection. Only 35.4\% of patients had maximal CRT reduction at 4 weeks. Twenty percent of treatment-naive and 34.8\% of non-naive patients had a week-4 CRT that was \&gt;35 μm thicker than the earlier occuring lowest CRT value (nadir). The time to maximal CRT reduction was not related to axial length, age, lens status, or history of injections. CONCLUSIONS: Optimal dosing interval for maximal CRT reduction may be less than 4 weeks for a significant proportion of patients. Most patients will be classified as complete responders if intervals less than 4 weeks are used to assess anti-VEGF treatment response. Disease load rather than eye size appears to be the driver of anti-VEGF treatment duration and therefore, dosing interval needs to be optimized in the cohort of short-term responders.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2019.11.004},
	author = {Bontzos, Georgios and Bagheri, Saghar and Ioanidi, Larissa and Kim, Ivana and Datseris, Ioannis and Gragoudas, Evangelos and Kabanarou, Stamatina and Miller, Joan and Tsilimbaris, Miltiadis and Vavvas, Demetrios G}
}
@article {603871,
	title = {A therapeutic trial of valganciclovir in patients with uveitis and positive Epstein-Barr virus early antigen D IgG titers.},
	journal = {Eur J Ophthalmol},
	volume = {26},
	number = {1},
	year = {2015},
	month = {2015 Dec 1},
	pages = {30-5},
	abstract = {PURPOSE: To evaluate the effectiveness of a therapeutic trial of valganciclovir in patients with uveitis with positive Epstein-Barr virus early antigen D immunoglobulin G titers (EBV EA-D). METHODS: We performed a retrospective chart review of 14 patients at the Massachusetts Eye Research and Surgery Institution who had uveitis with positive EBV EA-D but negative studies for all other causes of uveitis and were treated with valganciclovir 450 mg twice a day or valganciclovir 900 mg twice a day between January 2010 and August 2014. RESULTS: Nine of 14 patients, who had presumed EBV reactivation with associated intraocular inflammation, were successfully treated with valganciclovir: 3 of these were treated with valganciclovir 450 mg twice a day and 6 were treated with valganciclovir 900 mg twice a day. Five of 14 patients failed to respond to valganciclovir with persistent inflammation after at least 2 weeks of valganciclovir therapy, and were subsequently treated with immunomodulatory therapy to control inflammation. CONCLUSIONS: Uveitis can be caused by EBV infection/reactivation. A therapeutic trial with valganciclovir 450 mg twice a day for 1 month in patients with uveitis with positive EBV EA antibody may be beneficial.},
	issn = {1724-6016},
	doi = {10.5301/ejo.5000673},
	author = {Boonsopon, Sutasinee and Maghsoudlou, Armin and Kombo, Ninani E and Foster, C Stephen}
}
@article {1773451,
	title = {Assessment of Inner Blood-Retinal Barrier: Animal Models and Methods},
	journal = {Cells},
	volume = {12},
	number = {20},
	year = {2023},
	month = {2023 Oct 12},
	abstract = {Proper functioning of the neural retina relies on the unique retinal environment regulated by the blood-retinal barrier (BRB), which restricts the passage of solutes, fluids, and toxic substances. BRB impairment occurs in many retinal vascular diseases and the breakdown of BRB significantly contributes to disease pathology. Understanding the different molecular constituents and signaling pathways involved in BRB development and maintenance is therefore crucial in developing treatment modalities. This review summarizes the major molecular signaling pathways involved in inner BRB (iBRB) formation and maintenance, and representative animal models of eye diseases with retinal vascular leakage. Studies on Wnt/β-catenin signaling are highlighted, which is critical for retinal and brain vascular angiogenesis and barriergenesis. Moreover, multiple in vivo and in vitro methods for the detection and analysis of vascular leakage are described, along with their advantages and limitations. These pre-clinical animal models and methods for assessing iBRB provide valuable experimental tools in delineating the molecular mechanisms of retinal vascular diseases and evaluating therapeutic drugs.},
	keywords = {Animals, Blood-Retinal Barrier, Models, Animal, Retina, Retinal Diseases, Vascular Diseases},
	issn = {2073-4409},
	doi = {10.3390/cells12202443},
	author = {Bora, Kiran and Kushwah, Neetu and Maurya, Meenakshi and Pavlovich, Madeline C and Wang, Zhongxiao and Chen, Jing}
}
@article {1645451,
	title = {Endothelial Cell Transcytosis Assay as an In Vitro Model to Evaluate Inner Blood-Retinal Barrier Permeability},
	journal = {J Vis Exp},
	number = {184},
	year = {2022},
	month = {2022 Jun 07},
	abstract = {Dysfunction of the blood-retinal barrier (BRB) contributes to the pathophysiology of several vascular eye diseases, often resulting in retinal edema and subsequent vision loss. The inner blood-retinal barrier (iBRB) is mainly composed of retinal vascular endothelium with low permeability under physiological conditions. This feature of low permeability is tightly regulated and maintained by low rates of paracellular transport between adjacent retinal microvascular endothelial cells, as well as transcellular transport (transcytosis) through them. The assessment of retinal transcellular barrier permeability may provide fundamental insights into iBRB integrity in health and disease. In this study, we describe an endothelial cell (EC) transcytosis assay, as an in vitro model for evaluating iBRB permeability, using human retinal microvascular endothelial cells (HRMECs). This assay assesses the ability of HRMECs to transport transferrin and horseradish peroxidase (HRP) in receptor- and caveolae-mediated transcellular transport processes, respectively. Fully confluent HRMECs cultured on porous membrane were incubated with fluorescent-tagged transferrin (clathrin-dependent transcytosis) or HRP (caveolae-mediated transcytosis) to measure the levels of transferrin or HRP transferred to the bottom chamber, indicative of transcytosis levels across the EC monolayer. Wnt signaling, a known pathway regulating iBRB, was modulated to demonstrate the caveolae-mediated HRP-based transcytosis assay method. The EC transcytosis assay described here may provide a useful tool for investigating the molecular regulators of EC permeability and iBRB integrity in vascular pathologies and for screening drug delivery systems.},
	keywords = {Blood-Retinal Barrier, Endothelial Cells, Humans, Permeability, Transcytosis, Transferrins},
	issn = {1940-087X},
	doi = {10.3791/64076},
	author = {Bora, Kiran and Wang, Zhongxiao and Yemanyi, Felix and Maurya, Meenakshi and Blomfield, Alexandra K and Tomita, Yohei and Chen, Jing}
}
@article {1328874,
	title = {A Comprehensive Surgical Curriculum Reduced Intra-operative Complication Rates of Resident-performed Cataract Surgeries},
	journal = {J Surg Educ},
	volume = {76},
	number = {1},
	year = {2019},
	month = {2019 Jan - Feb},
	pages = {150-157},
	abstract = {OBJECTIVES: To evaluate the impact of a comprehensive cataract surgery curriculum on the incidence of intraoperative complications. DESIGN: We retrospectively compared the total number of cataract surgeries that the residents performed in all of the teaching sites, and the incidences of intraoperative complications (anterior capsule tear, posterior capsule rent, vitreous loss, anterior vitrectomy, zonular dialysis, iris trauma, hemorrhage, dropped lens fragment, corneal wound burn, incorrect intraocular lens) for the surgeries performed at Massachusetts Eye \&amp; Ear by residents in the pre-intervention group (residents graduating in 2004 and 2005), before the implementation of a surgical curriculum, and the residents in the post-intervention group (residents graduating in 2014 and 2015). SETTING: Ophthalmology residency program at a major academic institution. PARTICIPANTS: Residents graduating in 2004, 2005, 2014, and 2015. RESULTS: We reviewed 4373 charts. 2086 of those surgeries were performed at Massachusetts Eye \&amp; Ear. The incidence of posterior capsule rent/vitreous loss/anterior vitrectomy was lower in the post-intervention group (1.4\% versus 7.7\%, p\&nbsp;\&lt;\&nbsp;0.0001). Other complications were also lower in the post-intervention group. CONCLUSIONS: Implementation of a comprehensive cataract surgery curriculum focusing on pre-operative, intra-operative and post-operative interventions, with an emphasis on patient outcomes resulted in a decrease in the rate of intraoperative complications.},
	issn = {1878-7452},
	doi = {10.1016/j.jsurg.2018.07.009},
	author = {Borboli-Gerogiannis, Sheila and Jeng-Miller, Karen W and Koulisis, Nicole and Moustafa, Giannis A and Chang, Kenneth K and Chen, Sherleen H and Gardiner, Matthew F and Greenstein, Scott H and Luo, Zhonghui and Chen, Teresa C and Loewenstein, John I and Miller, Joan W and Haviland, Miriam J and Kloek, Carolyn E}
}
@article {1773501,
	title = {Indications for Magnetic Resonance Imaging in Patients With Behcet Uveitis},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 Oct 16},
	abstract = {BACKGROUND: Behcet disease is a systemic vasculitis, which may involve the eyes and central nervous system. The true prevalence of neurological involvement is not precisely known but may be associated with ocular involvement. This study investigates the association between Behcet uveitis and neuro-Behcet disease. METHODS: A retrospective single-center analysis was conducted for consecutive patients with Behcet uveitis at the Massachusetts Eye Research and Surgery Institution. Uveitis characteristics, neurological symptoms, fluorescein fundus angiography, and MRI results were recorded. RESULTS: Our population included 108 patients with Behcet uveitis, and 26 (24.1\%) were found to have neurological involvement associated with Behcet disease. Optic nerve leakage on fundus angiography and neurological symptoms were associated with an increased risk of neurological involvement. Three cases (11.5\%) were nonparenchymal, while 23 (88.5\%) were parenchymal with lesions in the cortex, subcortical white matter, thalamus, basal ganglia, and brainstem. CONCLUSIONS: There is a high comorbidity between ocular and neurological involvement in Behcet disease. Careful assessment of neurological symptoms and baseline fluorescein fundus angiography are recommended for patients with Behcet disease. MRI has a high diagnostic yield and should be pursued if there is concern for progressive or pre-existing neurological involvement.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000002018},
	author = {Borelli, Anna and Behr, Jordan and Ruggeri, Maria and Han, Mini and Zhou, Yujia and Foster, C Stephen}
}
@article {742231,
	title = {Treatment of Fuchs Endothelial Dystrophy by Descemet Stripping Without Endothelial Keratoplasty.},
	journal = {Cornea},
	volume = {35},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {1267-73},
	abstract = {PURPOSE: To evaluate the effect of deliberate removal of the central Descemet membrane on endothelial function and morphology in patients with Fuchs endothelial dystrophy (FED) and cataract undergoing phacoemulsification. METHODS: In this retrospective case series, patients with FED and visually significant cataract underwent phacoemulsification in an academic cornea practice in Boston, MA. Four millimeters of the central Descemet membrane was stripped and removed after intraocular lens insertion. Vision, corneal pachymetry, and confocal imaging of the endothelial anatomy were performed before surgery and at 1, 3, 6, and 12 months after surgery. Patients were classified as fast responders, responders, slow responders, and nonresponders on the basis of postoperative time to resolution of corneal edema with visible central endothelial mosaic. RESULTS: Eleven patients (13 eyes) aged 51 to 91 years were included in the study. No eyes had countable central endothelial cells by confocal imaging before surgery. Preoperative visual acuity ranged from 20/25 to 20/400. All corneas showed stromal and microcystic edema in the area of Descemet stripping at days 1 and 7 after surgery. Four eyes demonstrated resolution of corneal edema with visible central endothelial cell mosaic (range: 410-864 cells/mm) by postoperative month 1 with visual acuity ranging between 20/25 and 20/40. Four additional eyes demonstrated a similar response by postoperative month 3 and an additional 2 eyes had resolution of corneal edema with an intact central endothelial mosaic at postoperative month 6 or later. Cell counts (range: 428-864 cells/mm) were maintained in all 10 responders at the last follow-up visit (range: postoperative months 6-24). Final vision ranged from 20/15 to 20/20 in these 10 eyes with the exception of 2 eyes with retinal pathology. Three eyes required endothelial keratoplasty. CONCLUSIONS: Repopulation of the central corneal endothelium with corneal deturgescence can occur after deliberate central Descemet stripping in patients with FED who underwent cataract removal. This may offer a novel treatment for patients with FED that could reduce the need for endothelial transplantation. Further studies are needed to delineate the optimal patient population for Descemet stripping because not all patients will respond to this intervention.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000915},
	author = {Borkar, Durga S and Veldman, Peter and Colby, Kathryn A}
}
@article {1347428,
	title = {Incidence of Management Changes at the Postoperative Week 1 Visit after Cataract Surgery: Results from the Perioperative Care for IntraOcular Lens Study},
	journal = {Am J Ophthalmol},
	volume = {199},
	year = {2019},
	month = {2019 Mar},
	pages = {94-100},
	abstract = {PURPOSE: To ascertain the incidence of unexpected management changes at the postoperative week 1 visit in asymptomatic patients who have had an uncomplicated cataract surgery and a routine postoperative day 1 examination. DESIGN: Retrospective observational study. METHODS: A retrospective chart review was conducted of all cases of cataract extraction by phacoemulsification with intraocular lens insertion performed by the Comprehensive Ophthalmology Service at Massachusetts Eye and Ear between January 1, 2014 and December 31, 2014. The preoperative consultation, operative report, and postoperative day 1 and week 1 (postoperative days 5-14) visits were reviewed. Cases with intraoperative complications, as well as clinical findings at postoperative day 1 requiring close follow-up, were excluded. The main outcome measure was incidence of unexpected management changes at the postoperative week 1 visit after cataract surgery, defined as an unanticipated change in postoperative drops, additional procedures, or urgent referral to a specialty service. RESULTS: Overall, 1938 surgical cases of 1471 patients were reviewed, and 1510 cases (77.9\%) underwent uncomplicated phacoemulsification with intraocular lens implantation with a routine postoperative day 1 examination. Of these 1510 cases, 238 (15.8\%) reported symptoms at the postoperative week 1 visit, including flashes, floaters, redness, pain, or decreased vision, which warranted an examination. In total, 1272 cases were asymptomatic, and only 11 of these cases (0.9\%) had an unexpected management change at postoperative week 1. Eight of 11 patients were asymptomatic steroid responders requiring alteration of their postoperative drops. Two of these patients had an intraocular pressure \&gt;30\&nbsp;mm Hg. CONCLUSIONS: Unexpected management changes at the postoperative week 1 timepoint after cataract surgery are rare in asymptomatic patients who have had uncomplicated cataract surgery and a routine postoperative day 1 examination. Limited data are available to outline an optimal postoperative regimen after cataract surgery. The results of this study suggest that postoperative week 1 examinations could potentially be performed on an as-needed basis in the appropriate subgroup of patients after cataract surgery.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.10.013},
	author = {Borkar, Durga S and La{\'\i}ns, In{\^e}s and Eton, Emily A and Koulisis, Nicole and Moustafa, Giannis A and van Zyl, Tav{\'e} and Kloek, Carolyn E and Perioperative Care for IntraOcular Lens Study Group}
}
@article {1078716,
	title = {Association Between Thyroid Disease and Uveitis: Results From the Pacific Ocular Inflammation Study},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {6},
	year = {2017},
	month = {2017 Jun 01},
	pages = {594-599},
	abstract = {Importance: Common pathophysiological mechanisms may be responsible for immune dysregulation in both thyroid disease and uveitis. Studies investigating a possible association are limited. Objective: To determine the association between thyroid disease and uveitis. Design, Setting, and Participants: A retrospective, population-based case-control study was conducted from January 1, 2006, to December 31, 2007, among 217 061 members of the Kaiser Permanente Hawaii health system during the study period. A clinical diagnosis of uveitis was determined through a query of the electronic medical record followed by individual medical record review for confirmation by a uveitis specialist. Thyroid disease was determined based on International Classification of Diseases, Ninth Revision, coding. Two control groups were chosen at a 4:1 ratio for comparison with patients with uveitis. A logistic regression analysis was performed with uveitis as the main outcome variable and thyroid disease as the main predictor variable, while adjusting for age, sex, race, smoking status, and history of autoimmune disease. Data analysis was conducted between 2014 and 2016. Main Outcomes and Measures: A diagnosis of thyroid disease among patients with uveitis and respective controls. Results: Of the 224 patients with uveitis (127 women and 97 men; mean [SD] age, 54.1 [17.8] years) identified during the study period, 29 (12.9\%) had a diagnosis of thyroid disease, compared with 62 of 896 patients (6.9\%) in the control group (P = .01) and 78 of 896 patients (8.7\%) in the ophthalmology clinic control group (P = .06). Using the general Kaiser Permanente Hawaii population control group, patients who had thyroid disease had a 1.7-fold (95\% CI, 1.03-2.80; P = .04) higher odds of having uveitis compared with patients who did not have thyroid disease when controlling for age, sex, race, smoking status, and autoimmune disease. A similar association was found using the ophthalmology clinic control group (odds ratio, 1.8; 95\% CI, 1.1-2.9; P = .02) while adjusting for these factors. Conclusions and Relevance: These findings suggest that a history of thyroid disease has a weak to moderate association with uveitis. Similar autoimmune mechanisms could explain the pathogenesis of both conditions. If future studies corroborate these findings, they may have further clinical implications in the laboratory workup of uveitis.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.1009},
	author = {Borkar, Durga S and Homayounfar, Gelareh and Tham, Vivien M and Ray, Kathryn J and Vinoya, Aleli C and Uchida, Aileen and Acharya, Nisha R}
}
@article {1402572,
	title = {Techniques for improving ophthalmic studies performed on administrative databases},
	journal = {Ophthalmic Epidemiol},
	volume = {26},
	number = {3},
	year = {2019},
	month = {2019 Jun},
	pages = {147-149},
	issn = {1744-5086},
	doi = {10.1080/09286586.2018.1554160},
	author = {Borkar, Durga S and Sobrin, Lucia and Hubbard, Rebecca A and Kempen, John H and VanderBeek, Brian L}
}
@article {1351137,
	title = {Parry-Romberg syndrome vasculopathy and its treatment with botulinum toxin},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {30},
	number = {1},
	year = {2014},
	month = {2014 Jan-Feb},
	pages = {e22-5},
	abstract = {Parry-Romberg syndrome is a rare condition characterized by progressive, hemifacial atrophy, hair loss, enophthalmos, retinal vasculopathy occasionally associated with hemicranial pain syndrome (secondary trigeminal neuralgia). The cause of the condition is unknown; however, substantial evidence suggests that vasculopathy plays a significant role in the genesis of the neurologic damage and facial lipodystrophy. Herein describes a case of Parry-Romberg syndrome treated with repetitive botulinum type A toxin injections, with almost complete resolution of severe chronic pain.},
	keywords = {Botulinum Toxins, Type A, Facial Hemiatrophy, Female, Humans, Injections, Intradermal, Magnetic Resonance Imaging, Middle Aged, Neuromuscular Agents, Technetium, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31828de9c0},
	author = {Borodic, Gary E and Caruso, Paul and Acquadro, Martin and Chick, Sarah}
}
@article {1363248,
	title = {Use of fillers as adjunct therapy for the treatment of lower face hemifacial spasm},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {3},
	year = {2013},
	month = {2013 May-Jun},
	pages = {225-6},
	abstract = {The treatment of hemifacial spasm with periorbital injections of higher doses of botulinum toxin can create disfiguring and undesirable weakness in the lower face during active facial movements. The use of asymmetric hyaluronidate filler injections to the lower face provides a refinement allowing for a lowered neurotoxin dose. The filler creates a ballasting effect and involuntary facial movement. The conventional filler effect also further reduces asymmetric nasolabial folds and marionette lines. Fifteen of 18 patients with lower facial spasms found the filler toxin combination an improvement over neurotoxin alone.},
	keywords = {Botulinum Toxins, Type A, Drug Therapy, Combination, Facial Asymmetry, Hemifacial Spasm, Humans, Hyaluronic Acid, Injections, Intradermal, Neuromuscular Agents},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e318289577e},
	author = {Borodic, Gary E}
}
@article {1603855,
	title = {Evaluation of the blinq vision scanner for detection of amblyopia and strabismus},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Jul 08},
	abstract = {PURPOSE: To report the results of a clinical study designed to evaluate the accuracy of the blinq pediatric vision scanner, which detects amblyopia and strabismus directly by means of retinal polarization scanning, unlike other vision screening devices, which infer possible disease based on detection of refractive risk factors. METHODS: Subjects 1-20 years of age were prospectively enrolled in this cross-sectional diagnostic accuracy study with planned enrollment of 200. All enrolled subjects were tested by individuals masked to the diagnosis, followed by complete ophthalmologic examination by pediatric ophthalmologists masked to the screening result. Patients previously treated for amblyopia or strabismus were analyzed separately. RESULTS: The study cohort comprised 193 subjects, 53 of whom had been previously treated, leaving 140 treatment-na{\"\i}ve subjects, including 65 (46\%) with amblyopia or strabismus, 11 (8\%) with risk factors/suspected binocular vision deficit without amblyopia/strabismus, and 64 (46\%) controls. Sensitivity was 100\%, with all 66 patients with referral-warranted ocular disease referred. Five patients with intermittent strabismus receiving pass results were deemed "acceptable pass" when considering patient risk factors and amblyogenic potential. Specificity was 91\%, with 7 incorrect referrals. Subanalysis of children aged 2-8 years (n = 92) provided similar results (sensitivity 100\%; specificity 89\%). CONCLUSIONS: In this study cohort, the blinq showed very high sensitivity and specificity for detecting referral-warranted amblyopia and strabismus. Implementation of the device in vision screening programs could lead to improved rates of disease detection and reduction in false referrals.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2021.02.011},
	author = {Bosque, Lorenzo E and Yamarino, Cailyn R and Salcedo, Natalia and Schneier, Andrew J and Gold, Robert S and Blumenfeld, Louis C and Hunter, David G}
}
@article {1522731,
	title = {Outcomes of Bilateral Cataract Surgery in Infants 7 to 24 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry},
	journal = {Ophthalmology},
	volume = {128},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {302-308},
	abstract = {PURPOSE: To evaluate outcomes of bilateral cataract surgery in children aged 7 to 24 months and compare rates of adverse events (AEs) with other Toddler Aphakia and Pseudophakia Study (TAPS) registry outcomes. DESIGN: Retrospective clinical study at 10 Infant Aphakia Treatment Study (IATS) sites. Statistical analyses comparing this cohort with previously reported TAPS registry cohorts. PARTICIPANTS: Children enrolled in the TAPS registry between 2004 and\&nbsp;2010. METHODS: Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement at age 7 to 24 months with 5 years of postsurgical follow-up. MAIN OUTCOME MEASURES: Visual acuity (VA), occurrence of strabismus, AEs, and reoperations. RESULTS: A total of 40 children (76 eyes) who underwent bilateral cataract surgery with primary posterior capsulectomy were identified with a median age at cataract surgery of 11 months (7-23); 68\% received a primary IOL. Recurrent visual axis opacification (VAO) occurred in 7.5\% and was associated only with the use of an IOL (odds ratio, 6.10; P\&nbsp;= 0.005). Glaucoma suspect (GS) was diagnosed in 2.5\%, but no child developed glaucoma. In this bilateral cohort, AEs (8/40, 20\%), including glaucoma or GS and VAO, and reoperations occurred in a similar proportion to that of the published unilateral TAPS cohort. When analyzed with children aged 1 to 7 months at bilateral surgery, the incidence of AEs and glaucoma or GS correlated strongly with age at surgery (P\&nbsp;=\&nbsp;0.011/0.004) and glaucoma correlated with microcornea (P\&nbsp;= 0.040) but not with IOL insertion (P\&nbsp;= 0.15). CONCLUSIONS: Follow-up to age 5 years after bilateral cataract surgery in children aged 7 to 24 months reveals a low rate of VAO and very rare glaucoma or GS diagnosis compared with infants with cataracts operated at \&lt; 7 months of age despite primary IOL implantation in most children in the group aged 7 to 24 months. The use of an IOL increases the risk of VAO irrespective of age at surgery.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.07.020},
	author = {Bothun, Erick D and Wilson, M Edward and Yen, Kimberly G and Anderson, Jill S and Weil, Natalie C and Loh, Allison R and Morrison, David and Freedman, Sharon F and Plager, David A and VanderVeen, Deborah K and Traboulsi, Elias I and Hodge, David O and Lambert, Scott R and Toddler Aphakia and Pseudophakia Study}
}
@article {1504084,
	title = {Outcomes of Bilateral Cataracts Removed in Infants 1 to 7 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry},
	journal = {Ophthalmology},
	volume = {127},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {501-510},
	abstract = {PURPOSE: To evaluate outcomes of bilateral cataract surgery in infants 1 to 7 months of age performed by Infant Aphakia Treatment Study (IATS) investigators during IATS recruitment and to compare them with IATS unilateral outcomes. DESIGN: Retrospective case series review at 10 IATS sites. PARTICIPANTS: The Toddler Aphakia and Pseudophakia Study (TAPS) is a registry of children treated by surgeons who participated in the IATS. METHODS: Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement during IATS enrollment years 2004 through\&nbsp;2010. MAIN OUTCOME MEASURES: Visual acuity (VA), strabismus, adverse events (AEs), and reoperations. RESULTS: One hundred seventy-eight eyes (96 children) were identified with a median age of 2.5 months (range, 1-7 months) at the time of cataract surgery. Forty-two eyes (24\%) received primary IOL implantation. Median VA of the better-seeing eye at final study visit closest to 5 years of age with optotype VA testing was 0.35 logarithm of the minimum angle of resolution (logMAR; optotype equivalent, 20/45; range, 0.00-1.18 logMAR) in both aphakic and pseudophakic children. Corrected VA was excellent (\&lt;20/40) in 29\% of better-seeing eyes, 15\% of worse-seeing eyes. One percent showed poor acuity (>=20/200) in the better-seeing eye, 12\% in the worse-seeing eye. Younger age at surgery and smaller (\&lt;9.5 mm) corneal diameter at surgery conferred an increased risk for glaucoma or glaucoma suspect designation (younger age: odds ratio [OR], 1.44; P\&nbsp;= 0.037; and smaller cornea: OR, 3.95; P\&nbsp;= 0.045). Adverse events also were associated with these 2 variables on multivariate analysis (younger age: OR, 1.36; P\&nbsp;= 0.023; and smaller cornea: OR, 4.78; P\&nbsp;= 0.057). Visual axis opacification was more common in pseudophakic (32\%) than aphakic (8\%) eyes (P\&nbsp;= 0.009). Unplanned intraocular reoperation occurred in 28\% of first enrolled eyes (including glaucoma surgery in 10\%). CONCLUSIONS: Visual acuity after bilateral cataract surgery in infants younger than 7 months is good, despite\&nbsp;frequent systemic and ocular comorbidities. Although aphakia management did not affect VA outcome or AE incidence, IOL placement increased the risk of visual axis opacification. Adverse events and glaucoma correlated with a younger age at surgery and glaucoma correlated with the presence of microcornea.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.10.039},
	author = {Bothun, Erick D and Wilson, M Edward and VanderVeen, Deborah K and Plager, David A and Freedman, Sharon F and Trivedi, Rupal H and Traboulsi, Elias I and Anderson, Jill S and Loh, Allison R and Yen, Kimberly G and Weil, Natalie C and Morrison, David and Lambert, Scott R}
}
@article {1430520,
	title = {Outcomes of Unilateral Cataracts in Infants and Toddlers 7 to 24 Months of Age: Toddler Aphakia and Pseudophakia Study (TAPS)},
	journal = {Ophthalmology},
	volume = {126},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {1189-1195},
	abstract = {PURPOSE: To evaluate outcomes of unilateral cataract surgery in children 7 to 24 months of age. DESIGN: Retrospective case series at 10 Infant Aphakia Treatment Study (IATS) sites. PARTICIPANTS: The Toddler Aphakia and Pseudophakia Study is a registry of children treated by surgeons who participated in the IATS. METHODS: Children underwent unilateral cataract surgery with or without intraocular lens (IOL) placement during the IATS enrollment years of 2004 and\&nbsp;2010. MAIN OUTCOME MEASURES: Intraoperative complications, adverse events (AEs), visual acuity, and strabismus. RESULTS: Fifty-six children were included with a mean postoperative follow-up of 47.6 months. Median age at cataract surgery was 13.9 months (range, 7.2-22.9). Ninety-two percent received a primary IOL. Intraoperative complications occurred in 4 patients (7\%). At 5 years of age, visual acuity of treated eyes was very good (>=20/40) in 11\% and poor (<=20/200) in 44\%. Adverse events were identified in 24\%, with a 4\% incidence of glaucoma suspect. An additional unplanned intraocular surgery occurred in 14\% of children. Neither AEs nor intraocular reoperations were more common for children with surgery at 7 to 12 months of age than for those who underwent surgery at 13 to 24 months of age (AE rate, 21\% vs. 25\% [P\&nbsp;= 0.60]; reoperation rate, 13\% vs. 16\% [P\&nbsp;= 1.00]). CONCLUSIONS: Although most children underwent IOL implantation concurrent with unilateral cataract removal, the incidence of complications, reoperations, and glaucoma was low when surgery was performed between 7 and 24 months of age and compared favorably with same-site IATS data for infants undergoing surgery before 7 months of age. Our study showed that IOL implantation is relatively safe in children older than 6\&nbsp;months and younger than 2 years.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.03.011},
	author = {Bothun, Erick D and Wilson, M Edward and Traboulsi, Elias I and Diehl, Nancy N and Plager, David A and VanderVeen, Deborah K and Freedman, Sharon F and Yen, Kimberly G and Weil, Natalie C and Loh, Allison R and Morrison, David and Anderson, Jill S and Lambert, Scott R and Toddler Aphakia and Pseudophakia Study Group (TAPS)}
}
@article {959386,
	title = {Strabismus surgery outcomes in the Infant Aphakia Treatment Study (IATS) at age 5 years.},
	journal = {J AAPOS},
	volume = {20},
	number = {6},
	year = {2016},
	month = {2016 Dec},
	pages = {501-505},
	abstract = {PURPOSE: To report strabismus surgery frequency and outcomes after monocular infantile cataract surgery with or without IOL implantation. METHODS: The Infant Aphakia Treatment Study (IATS) is a randomized, multicenter clinical trial comparing treatment of aphakia with a primary IOL or contact lens in 114 infants with a unilateral congenital cataract. This report is a secondary outcome analysis of ocular motor data from IATS patients who underwent strabismus surgery prior to age 5\&nbsp;years. RESULTS: Strabismus surgery was performed in 45 (39\%) patients (contact lens group [CL], 37\%; IOL group, 42\% [P\&nbsp;=\&nbsp;0.70]). The indications for strabismus surgery were esotropia (62\%), exotropia (33\%), and hypertropia (4\%). Infants who underwent cataract surgery at a younger age were less likely to undergo strabismus surgery (28-48\&nbsp;days, 12/50 [24\%]; 49-210\&nbsp;days, 33/64 [52\%]; P\&nbsp;=\&nbsp;0.0037). Of the 42 patients who underwent strabismus surgery, 14 (33\%) had a postoperative distance alignment within 8(Δ) of orthotropia at age 5\&nbsp;years. The 5-year visual acuity of children with strabismus was the same whether or not strabismus surgery had been performed (1.10 logMAR with surgery vs 1.00 without [P\&nbsp;=\&nbsp;0.71]). CONCLUSIONS: In this study cohort, cataract surgery performed in the first 6\&nbsp;weeks of life was associated with a reduced frequency of strabismus surgery. Strabismus surgery outcomes in this population are guarded. Surgical improvement of strabismus does not appear to influence long-term visual acuity.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2016.09.014},
	author = {Bothun, Erick D and Lynn, Michael J and Christiansen, Stephen P and Kruger, Stacey J and VanderVeen, Deborah K and Neely, Dan E and Lambert, Scott R and Infant Aphakic Treatment Study}
}
@article {1647895,
	title = {Long-term strabismus outcomes after unilateral infantile cataract surgery in the Infant Aphakia Treatment Study},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Jul 14},
	abstract = {PURPOSE: To characterize long-term strabismus outcomes in children in the Infant Aphakia Treatment Study (IATS). METHODS: This study was a secondary data analysis of long-term ocular alignment characteristics of children aged 10.5 years who had previously been enrolled in a randomized clinical trial evaluating aphakic management after unilateral cataract surgery between 1 and 6 months of age. RESULTS: In the IATS study, 96 of 109 children (88\%) developed strabismus through age 10.5 years. Half of the 20 children who were orthophoric at distance through age 5 years maintained orthophoria at distance fixation at 10.5 years. Esotropia was the most common type of strabismus prior to age 5 years (56/109 [51\%]), whereas exotropia (49/109 [45\%]) was the most common type of strabismus at 10.5 years (esotropia, 21\%; isolated hypertropia, 17\%). Strabismus surgery had been performed on 52 children (48\%), with 18 of these (35\%) achieving microtropia \&lt;10Δ. Strabismus was equally prevalent in children randomized to contact lens care compared with those randomized to primary intraocular lens implantation (45/54 [83\%] vs 45/55 [82\%]; P = 0.8). Median visual acuity in the study eye was 0.56 logMAR (20/72) for children with orthotropia or microtropia \&lt;10Δ versus 1.30 logMAR (20/400) for strabismus >=10Δ (P = 0.0003). CONCLUSIONS: Strabismus-in particular, exotropia-is common irrespective of aphakia management 10 years following infant monocular cataract surgery. The delayed emergence of exotropia with longer follow-up indicates a need for caution in managing early esotropia in these children. Children with better visual acuity at 10 years of age are more likely to have better ocular alignment.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.05.003},
	author = {Bothun, Erick D and Shainberg, Marla J and Christiansen, Stephen P and VanderVeen, Deborah K and Neely, Dan E and Kruger, Stacey J and Cotsonis, George and Lambert, Scott R and Infant Aphakic Treatment Study}
}
@article {1653598,
	title = {Resolvin D2 uses multiple Ca2+ -dependent signaling pathways to stimulate mucin secretion in rat and human conjunctival goblet cells},
	journal = {J Cell Physiol},
	volume = {237},
	number = {10},
	year = {2022},
	month = {2022 10},
	pages = {3816-3833},
	abstract = {The mucin layer of the tear film is produced by goblet cells in the conjunctiva to protect the ocular surface and maintain homeostasis. The pro-resolving lipid mediator resolvin D2 (RvD2) biosynthesized from an omega 3 fatty acid actively terminates inflammation and regulates mucin secretion from conjunctival goblet cells. Our objective was to determine which Ca2+ -dependent signaling pathways RvD2 uses to stimulate conjunctival goblet cell function (CGC). We hypothesize that RvD2 activates multiple intracellular Ca2+ signaling pathways to stimulate CGC secretion. Rat and human CGCs were cultured from conjunctival explants. The amount of RvD2 receptor GPR18/DRV2 message and protein were determined. The intracellular concentration of Ca2+ ([Ca2+ ]i ) was measured in CGCs using a fluorescent Ca2+ dye and mucin secretion was determined by measuring protein secretion enzymatically with a lectin. Goblet cells were incubated with signaling pathway inhibitors before stimulation with RvD2 and [Ca2+ ]i or secretion was measured. In rat and human CGCs RvD2 receptor and in rat CGCs IP3 (a molecule that releases Ca2+ from intracellular organelles) receptors 1-3 were detected. In both species of CGC RvD2 increased [Ca2+ ]i similarly to RvD1. In rat CGCs, the increase in [Ca2+ ]i and secretion stimulated by RvD2 was significantly blocked by inhibitors to phospholipase (PL-) C and IP3 -receptor, but not protein kinase C. Increase in [Ca2+ ]i was blocked by the PLD inhibitor, but not the PLA2 inhibitor. Secretion was blocked by PLA2 inhibitor, but not the PLD inhibitor. An inhibitor of the epidermal growth factor receptor blocked the increase in [Ca2+ ]i by RvD2 in both species of CGCs. In CGCs RvD2 activates multiple intracellular signaling pathways that are Ca2+ -dependent, along with one Ca2+ -independent and one cAMP/protein kinase A-dependent pathway. Activation of these pathways stimulate mucin secretion from rat and human CGCs into the tear film contributing to ocular surface homeostasis and health.},
	keywords = {Animals, Calcium, Cells, Cultured, Conjunctiva, Cyclic AMP-Dependent Protein Kinases, Docosahexaenoic Acids, ErbB Receptors, Goblet Cells, Humans, Lectins, Mucins, Phospholipases, Phospholipases A2, Rats, Rats, Sprague-Dawley, Receptors, Cannabinoid, Signal Transduction},
	issn = {1097-4652},
	doi = {10.1002/jcp.30854},
	author = {Botten, Nora and Hodges, Robin R and Bair, Jeffrey and Utheim, Tor P and Serhan, Charles N and Yang, Menglu and Dartt, Darlene A.}
}
@article {1435396,
	title = {Resolvin D2 elevates cAMP to increase intracellular [Ca] and stimulate secretion from conjunctival goblet cells},
	journal = {FASEB J},
	volume = {33},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {8468-8478},
	abstract = {Under physiologic conditions, conjunctival goblet cells (CGCs) secrete mucins into the tear film to preserve ocular surface homeostasis. Specialized proresolving mediators (SPMs), like resolvins (Rvs), regulate secretion from CGCs and actively terminate inflammation. The purpose of this study was to determine if RvD2 stimulated mucin secretion and to investigate the cellular signaling components. Goblet cells were cultured from rat conjunctiva. Secretion was measured by an enzyme-linked lectin assay, change in intracellular [Ca] ([Ca]) using Fura-2, and cellular cAMP levels by ELISA. RvD2 (10-10 M) stimulated secretion, increased cellular cAMP levels and the [Ca]. RvD2-stimulated increase in [Ca] and secretion was blocked by Ca chelator 1,2-bis(2-aminophenoxy)ethane-,,{\textquoteright},{\textquoteright}-tetraacetic acid tetrakis and the PKA inhibitor -[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride but not by the cAMP exchange protein inhibitor α-[2-(3-chlorophenyl)hydrazinylidene]-5-(1,1-dimethylethyl)-b-oxo-3-isoxazolepropanenitrile. Forskolin, 3-isobutyl-1-methylxanthine, and 8-bromo-cAMP (8-Br-cAMP) increased [Ca]. Increasing cAMP with 8-Br-cAMP inhibited the increase in [Ca] stimulated by the cAMP-independent agonist cholinergic agonist carbachol. In conclusion, RvD2 uses both cellular cAMP and [Ca] to stimulate glycoconjugate secretion from CGCs, but the interaction of cAMP and [Ca] is context dependent. Thus RvD2 likely assists in the maintenance of the mucous layer of the tear film to sustain ocular surface homeostasis and has potential as a novel treatment for dry eye disease.-Botten, N., Hodges, R. R., Li, D., Bair, J. A., Shatos, M. A., Utheim, T. P., Serhan, C. N., Dartt, D. A. Resolvin D2 elevates cAMP to increase intracellular [Ca] and stimulate secretion from conjunctival goblet cells.},
	issn = {1530-6860},
	doi = {10.1096/fj.201802467R},
	author = {Botten, Nora and Hodges, Robin R and Li, Dayu and Bair, Jeffrey A and Shatos, Marie A and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1109776,
	title = {Transient Monocular Vision Loss on Awakening: A Benign Amaurotic Phenomenon},
	journal = {J Neuroophthalmol},
	volume = {37},
	number = {2},
	year = {2017},
	month = {2017 Jun},
	pages = {122-125},
	abstract = {BACKGROUND: Transient monocular vision loss (TMVL) is an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Our objective is to describe the phenomenon of TMVL present on awakening, which may represent a distinct and benign entity. METHODS: We performed a retrospective observational case series of 29 patients who experienced TMVL on awakening. Patients who described monocular dimming or blackout of vision were included, and those with blurred vision, concurrent eye pain, and binocular vision loss were excluded. Descriptive statistics were used to summarize the study population. RESULTS: Of the 29 patients we studied, 90\% (n = 26) were female and 48\% had crowded discs (cup-to-disc ratio <=0.2). The mean age was 45.4 years, although women were significantly younger than men (mean ages 43.4 and 62.7 years, respectively, P = 0.017). Brain magnetic resonance imaging and vascular imaging (magnetic resonance angiography, computed tomographic angiography, or carotid Doppler) were performed in 69\% and 55\% of cases, respectively, and were uniformly negative. In 14 patients for whom clear follow-up data could be obtained, no medically or visually significant sequelae of this syndrome were found, and 50\% experienced resolution of symptoms. CONCLUSIONS: Evaluation was uniformly negative when patients described waking with isolated vision loss in 1 eye with subsequent resolution, usually in less than 15 minutes. The natural history seems benign with symptoms frequently remitting spontaneously. This visual phenomenon may represent an autoregulatory failure resulting in a supply/demand mismatch during low-light conditions.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000451},
	author = {Bouffard, Marc A and Cornblath, Wayne T and Rizzo, Joseph F and Lee, Michael S and De Lott, Lindsey B and Eggenberger, Eric R and Torun, Nurhan}
}
@article {1213801,
	title = {Diplopia after Cataract Extraction},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Oct 09},
	pages = {1-6},
	abstract = {Diplopia after cataract extraction is an unexpected outcome for the patient and often a source of confusion for the physician, owing to its relative infrequency. This article reviews the pertinent literature on the subject. Mechanisms include anesthetic myotoxicity, surgical trauma, optical aberrations, cortical disorders in patients with congenital strabismus, and the unmasking of previously unnoticed ocular misalignment. As the population continues to age and cataract extraction is performed in increasing volume, familiarity with this uncommon but important outcome may help to clarify and effectively treat post-cataract-extraction diplopia.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353806},
	author = {Bouffard, Marc A and Cestari, Dean M}
}
@article {1043196,
	title = {Divergence Palsy due to Divalproex and Oxcarbazepine},
	journal = {Clin Neuropharmacol},
	year = {2017},
	month = {2017 Mar 09},
	abstract = {OBJECTIVE: This case series is the first to describe divergence palsy as an adverse effect of antiepileptic drug use. Diplopia is a common adverse effect of antiepileptic drugs, but no explanatory motility deficit has ever been reported. METHODS: We present 2 patients, 1 on oxcarbazepine and 1 on divalproex, each with a normal examination result between spells and divergency palsy when symptomatic. RESULTS: Discontinuation of the antiepileptic medication led to resolution of the episodes in both cases. Rechallenge with the offending agent after washout in one patient resulted in recurrence of diplopia and divergence palsy, both resolving after subsequent withdrawal of the antiepileptic. CONCLUSIONS: Antiepileptic drugs may cause divergence palsy.},
	issn = {1537-162X},
	doi = {10.1097/WNF.0000000000000210},
	author = {Bouffard, Marc Albert and Caplan, Louis R and Torun, Nurhan}
}
@article {1043201,
	title = {The Mystery of the Locking Eye},
	journal = {JAMA Neurol},
	volume = {74},
	number = {5},
	year = {2017},
	month = {2017 May 01},
	pages = {601-602},
	issn = {2168-6157},
	doi = {10.1001/jamaneurol.2016.5710},
	author = {Bouffard, Marc A and Torun, Nurhan}
}
@article {1603851,
	title = {Variation in Evolving Optic Neuritis},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {4},
	year = {2021},
	month = {2021 Dec 01},
	pages = {476-479},
	abstract = {BACKGROUND: The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. METHODS: Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. RESULTS: Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. CONCLUSIONS: This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001310},
	author = {Bouffard, Marc A and M Mallery, Robert and Liao, Yaping J and Torun, Nurhan}
}
@article {1282096,
	title = {Advances in Neuro-Ophthalmic Imaging},
	journal = {Semin Neurol},
	volume = {37},
	number = {5},
	year = {2017},
	month = {2017 Oct},
	pages = {566-579},
	issn = {1098-9021},
	doi = {10.1055/s-0037-1608765},
	author = {Bouffard, Marc A and Prasad, Sashank}
}
@article {913401,
	title = {Re-Treatment With Ethambutol After Toxic Optic Neuropathy},
	journal = {J Neuroophthalmol},
	volume = {37},
	number = {1},
	year = {2017},
	month = {2017 Mar},
	pages = {40-42},
	abstract = {There are no data in the literature regarding the safety of re-treatment with ethambutol for recurrent mycobacterial infection after prior ethambutol-induced optic neuropathy. We describe a patient who developed optic neuropathy attributed to ethambutol, recovered fully after drug withdrawal, and tolerated a 14-month long re-treatment 10 years later without developing recurrent optic neuropathy.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000445},
	author = {Bouffard, Marc A and Nathavitharana, Ruvandhi R and Yassa, David S and Torun, Nurhan}
}
@article {1304379,
	title = {Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe in 2015: magnitude, temporal trends and projections},
	journal = {Br J Ophthalmol},
	volume = {102},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {575-585},
	abstract = {BACKGROUND: Within a surveillance of the prevalence and causes of vision impairment in high-income regions and Central/Eastern Europe, we update figures through 2015 and forecast expected values in 2020.

METHODS: Based on a systematic review of medical literature, prevalence of blindness, moderate and severe vision impairment (MSVI), mild vision impairment and presbyopia was estimated for 1990, 2010, 2015, and 2020.

RESULTS: Age-standardised prevalence of blindness and MSVI for all ages decreased from 1990 to 2015 from 0.26\% (0.10-0.46) to 0.15\% (0.06-0.26) and from 1.74\% (0.76-2.94) to 1.27\% (0.55-2.17), respectively. In 2015, the number of individuals affected by blindness, MSVI and mild vision impairment ranged from 70 000, 630 000 and 610 000, respectively, in Australasia to 980 000, 7.46 million and 7.25 million, respectively, in North America and 1.16 million, 9.61 million and 9.47 million, respectively, in Western Europe. In 2015, cataract was the most common cause for blindness, followed by age-related macular degeneration (AMD), glaucoma, uncorrected refractive error, diabetic retinopathy and cornea-related disorders, with declining burden from cataract and AMD over time. Uncorrected refractive error was the leading cause of MSVI.

CONCLUSIONS: While continuing to advance control of cataract and AMD as the leading causes of blindness remains a high priority, overcoming barriers to uptake of refractive error services would address approximately half of the MSVI burden. New data on burden of presbyopia identify this entity as an important public health problem in this population. Additional research on better treatments, better implementation with existing tools and ongoing surveillance of the problem is needed.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2017-311258},
	author = {Bourne, Rupert R A and Jonas, Jost B and Bron, Alain M and Cicinelli, Maria Vittoria and Das, Aditi and Flaxman, Seth R and Friedman, David S and Keeffe, Jill E and Kempen, John H and Leasher, Janet and Limburg, Hans and Naidoo, Kovin and Pesudovs, Konrad and Peto, Tunde and Saadine, Jinan and Silvester, Alexander J and Tahhan, Nina and Taylor, Hugh R and Varma, Rohit and Wong, Tien Y and Resnikoff, Serge}
}
@article {1179216,
	title = {Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis},
	journal = {Lancet Glob Health},
	volume = {5},
	number = {9},
	year = {2017},
	month = {2017 Sep},
	pages = {e888-e897},
	abstract = {BACKGROUND: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. METHODS: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). FINDINGS: Globally, of the 7{\textperiodcentered}33 billion people alive in 2015, an estimated 36{\textperiodcentered}0 million (80\% uncertainty interval [UI] 12{\textperiodcentered}9-65{\textperiodcentered}4) were blind (crude prevalence 0{\textperiodcentered}48\%; 80\% UI 0{\textperiodcentered}17-0{\textperiodcentered}87; 56\% female), 216{\textperiodcentered}6 million (80\% UI 98{\textperiodcentered}5-359{\textperiodcentered}1) people had moderate to severe visual impairment (2{\textperiodcentered}95\%, 80\% UI 1{\textperiodcentered}34-4{\textperiodcentered}89; 55\% female), and 188{\textperiodcentered}5 million (80\% UI 64{\textperiodcentered}5-350{\textperiodcentered}2) had mild visual impairment (2{\textperiodcentered}57\%, 80\% UI 0{\textperiodcentered}88-4{\textperiodcentered}77; 54\% female). Functional presbyopia affected an estimated 1094{\textperiodcentered}7 million (80\% UI 581{\textperiodcentered}1-1686{\textperiodcentered}5) people aged 35 years and older, with 666{\textperiodcentered}7 million (80\% UI 364{\textperiodcentered}9-997{\textperiodcentered}6) being aged 50 years or older. The estimated number of blind people increased by 17{\textperiodcentered}6\%, from 30{\textperiodcentered}6 million (80\% UI 9{\textperiodcentered}9-57{\textperiodcentered}3) in 1990 to 36{\textperiodcentered}0 million (80\% UI 12{\textperiodcentered}9-65{\textperiodcentered}4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38{\textperiodcentered}4\%), population ageing after accounting for population growth (34{\textperiodcentered}6\%), and reduction in age-specific prevalence (-36{\textperiodcentered}7\%). The number of people with moderate and severe visual impairment also increased, from 159{\textperiodcentered}9 million (80\% UI 68{\textperiodcentered}3-270{\textperiodcentered}0) in 1990 to 216{\textperiodcentered}6 million (80\% UI 98{\textperiodcentered}5-359{\textperiodcentered}1) in 2015. INTERPRETATION: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world{\textquoteright}s population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels. FUNDING: Brien Holden Vision Institute.},
	issn = {2214-109X},
	doi = {10.1016/S2214-109X(17)30293-0},
	author = {Bourne, Rupert R A and Flaxman, Seth R and Braithwaite, Tasanee and Cicinelli, Maria V and Das, Aditi and Jonas, Jost B and Keeffe, Jill and Kempen, John H and Leasher, Janet and Limburg, Hans and Naidoo, Kovin and Pesudovs, Konrad and Resnikoff, Serge and Silvester, Alex and Stevens, Gretchen A and Tahhan, Nina and Wong, Tien Y and Taylor, Hugh R and Vision Loss Expert Group}
}
@article {987941,
	title = {Evolving Surgical Interventions in the Treatment of Glaucoma.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	month = {2017},
	pages = {91-95},
	abstract = {Interventions in the treatment of mild to moderate glaucoma have evolved to include a group of procedures collectively named "Minimally Invasive Glaucoma Surgery (MIGS)." These procedures are less invasive than traditional filtering surgery and setons and offer the benefit of an improved side-effect profile. A review of current published literature has shown that these procedures offer lower intraocular pressure, decrease reliance on topical medications, have no negative effect on refractive outcomes, and can be safely done following failed tube surgery.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228393},
	author = {Bovee, Courtney E and Pasquale, Louis R}
}
@article {1282101,
	title = {Endoscopic Vitrectomy for Microcornea, Posterior Megalolenticonus, Persistent Fetal Vasculature, Coloboma Syndrome},
	journal = {Ophthalmology},
	volume = {124},
	number = {12},
	year = {2017},
	month = {2017 Dec},
	pages = {1742},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.07.028},
	author = {Bowe, Theodore and Rahmani, Safa and Yonekawa, Yoshihiro}
}
@article {1511481,
	title = {Virtual Visits in Ophthalmology: Timely Advice for Implementation During the COVID-19 Public Health Crisis},
	journal = {Telemed J E Health},
	volume = {26},
	number = {9},
	year = {2020},
	month = {2020 09},
	pages = {1113-1117},
	abstract = {Virtual visits (VVs) are necessitated due to the public health crisis and social distancing mandates due to COVID-19. However, these have been rare in ophthalmology. Over 3.5 years of conducting \&gt;350 ophthalmological VVs, our group has gained numerous insights into best practices. This communication shares these experiences with the medical community to support patient care during this difficult time and beyond. We highlight that mastering the technological platform of choice, optimizing lighting, camera positioning, and "eye contact," being thoughtful and creative with the virtual eye examination, and ensuring good documenting and billing will make a successful and efficient VV. Moreover, we think these ideas will stimulate further VV creativity and expertise to be developed in ophthalmology and across medicine. This approach, holds promise for increasing its adoption after the crisis has passed.},
	issn = {1556-3669},
	doi = {10.1089/tmj.2020.0121},
	author = {Bowe, Theodore and Hunter, David G and Mantagos, Iason S and Kazlas, Melanie and Jastrzembski, Benjamin G and Gaier, Eric D and Massey, Gordon and Franz, Kristin and Schumann, Caitlin and Brown, Christina and Meyers, Heather and Shah, Ankoor S}
}
@article {1629459,
	title = {Timing of Ocular Hypertension After Pediatric Closed-Globe Traumatic Hyphema: Implications for Surveillance},
	journal = {Am J Ophthalmol},
	volume = {233},
	year = {2022},
	month = {2022 01},
	pages = {135-143},
	abstract = {PURPOSE: To evaluate the timing of ocular hypertension (OHT) after pediatric closed-globe injury (CGI) and traumatic hyphema. We hypothesize that OHT will occur at different times based on injury characteristics. DESIGN: Retrospective, cohort study. METHODS: Setting: Single-center, tertiary-care, pediatric hospital. PARTICIPANTS: Subjects included patients <=18 years of age at the time of injury who suffered CGI and traumatic hyphema between 2002 and 2019. Observation Procedure(s): Intraocular pressure and injury demographics were abstracted for every visit after injury. OHT was defined as \&gt;21 mm Hg at presentation or after a reading of <=21 mm Hg at a prior visit. MAIN OUTCOME MEASURES: The primary outcome measure was the timing of OHT categorized into 4 periods: presentation, acute (days 1-7), subacute (days 8-28), or late (day \&gt;28). Secondary outcome measures were identification of risks factors for OHT by multivariable logistic regression. RESULTS: OHT occurred in 119 of the 305 (39\%) subject eyes. OHT occurred in 35 patients at presentation, 69 times acutely, 35 times subacutely, and 36 times late. Pupil damage predicted acute-period OHT (P = .004). OHT at presentation predicted subacute period OHT (P = .004). Iridodialysis and cataract predicted late-period OHT (P = .007 and P \&lt; .001, respectively). CONCLUSIONS: OHT after CGI and traumatic hyphema in pediatric patients is common. Injury demographics predict this complication. Integration of these risk factors with current literature allows proposal of a risk-stratification tool to guide efficient surveillance for OHT.},
	keywords = {Child, Cohort Studies, Humans, Hyphema, Intraocular Pressure, Ocular Hypertension, Retrospective Studies, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.04.033},
	author = {Bowe, Theodore and Serina, Anthony and Armstrong, Mikhayla and Welcher, Jennifer E and Adebona, Olumuyiwa and Gore, Charlotte and Staffa, Steven J and Zurakowski, David and Shah, Ankoor S}
}
@article {882896,
	title = {Driving with homonymous visual field loss: a review of the literature.},
	journal = {Clin Exp Optom},
	volume = {99},
	number = {5},
	year = {2016},
	month = {2016 Sep},
	pages = {402-18},
	abstract = {Driving is an important rehabilitation goal for patients with homonymous field defects (HFDs); however, whether or not people with HFDs should be permitted to drive is not clear. Over the last 15 years, there has been a marked increase in the number of studies evaluating the effects of HFDs on driving performance. This review of the literature provides a much-needed summary for practitioners and researchers, addressing the following topics: regulations pertaining to driving with HFDs, self-reported driving difficulties, pass rates in on-road tests, the effects of HFDs on lane position and steering stability, the effects of HFDs on scanning and detection of potential hazards, screening for potential fitness to drive, evaluating practical fitness to drive and the efficacy of interventions to improve driving of persons with HFDs. Although there is clear evidence from on-road studies that some people with HFDs may be rated as safe to drive, others are reported to have significant deficits in skills important for safe driving, including taking a lane position too close to one side of the travel lane, unstable steering and inadequate viewing (scanning) behaviour. Driving simulator studies have provided strong evidence of a wide range in compensatory scanning abilities and detection performance, despite similar amounts of visual field loss. Conventional measurements of visual field extent (in which eye movements are not permitted) do not measure such compensatory abilities and are not predictive of on-road driving performance. Thus, there is a need to develop better tests to screen people with HFDs for visual fitness to drive. We are not yet at a point where we can predict which HFD patient is likely to be a safe driver. Therefore, it seems only fair to provide an opportunity for individualised assessments of practical fitness to drive either on the road and/or in a driving simulator.},
	issn = {1444-0938},
	doi = {10.1111/cxo.12425},
	author = {Bowers, Alex R}
}
@article {913406,
	title = {Bioptic Telescope Use and Driving Patterns of Drivers with Age-Related Macular Degeneration.},
	journal = {Transl Vis Sci Technol},
	volume = {5},
	number = {5},
	year = {2016},
	month = {2016 Sep},
	pages = {5},
	abstract = {PURPOSE: To investigate the telescope use and driving patterns of bioptic drivers with age-related macular degeneration (AMD). METHODS: A questionnaire addressing telescope use and driving patterns was administered by telephone interview to three groups of bioptic drivers: AMD (n = 31; median 76 years); non-AMD first licensed with a bioptic (n = 38; 53 years); and non-AMD first licensed without a bioptic (n = 47; 37 years). Driving patterns of bioptic AMD drivers were also compared with those of normal vision (NV) drivers (n = 36; 74 years) and nonbioptic AMD drivers (n = 34; 79 years). RESULTS: Bioptic usage patterns of AMD drivers did not differ from those of the younger bioptic drivers and greater visual difficulty without the bioptic was strongly correlated with greater bioptic helpfulness. Bioptic AMD drivers were more likely to report avoidance of night driving than the age-similar NV drivers (P = 0.06). However, they reported less difficulty than the nonbioptic AMD drivers in all driving situations (P <= 0.02). Weekly mileages of bioptic AMD drivers were lower than those of the younger bioptic drivers (P \&lt; 0.001), but not the NV group (P = 0.54), and were higher than those of the nonbioptic AMD group (P \&lt; 0.001). CONCLUSIONS: Our results suggest that bioptic telescopes met the visual demands of drivers with AMD and that those drivers had relatively unrestricted driving habits. TRANSLATIONAL RELEVANCE: Licensure with a bioptic telescope may prolong driving of older adults with AMD; however, objective measures of bioptic use, driving performance, and safety are needed.},
	issn = {2164-2591},
	doi = {10.1167/tvst.5.5.5},
	author = {Bowers, Alex R and Sheldon, Sarah S and DeCarlo, Dawn K and Peli, Eli}
}
@article {1351138,
	title = {Driving with hemianopia: IV. Head scanning and detection at intersections in a simulator},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {3},
	year = {2014},
	month = {2014 Mar 13},
	pages = {1540-8},
	abstract = {PURPOSE: Using a driving simulator, we examined the effects of homonymous hemianopia (HH) on head scanning behaviors at intersections and evaluated the role of inadequate head scanning in detection failures. METHODS: Fourteen people with complete HH and without cognitive decline or visual neglect and 12 normally sighted (NV) current drivers participated. They drove in an urban environment following predetermined routes, which included multiple intersections. Head scanning behaviors were quantified at T-intersections (n = 32) with a stop or yield sign. Participants also performed a pedestrian detection task. The relationship between head scanning and detection was examined at 10 intersections. RESULTS: For HH drivers, the first scan was more likely to be toward the blind than the seeing hemifield. They also made a greater proportion of head scans overall to the blind side than did the NV drivers to the corresponding side (P = 0.003). However, head scan magnitudes of HH drivers were smaller than those of the NV group (P \&lt; 0.001). Drivers with HH had impaired detection of blind-side pedestrians due either to not scanning in the direction of the pedestrian or to an insufficient scan magnitude (left HH detected only 46\% and right HH 8\% at the extreme left and right of the intersection, respectively). CONCLUSIONS: Drivers with HH demonstrated compensatory head scan patterns, but not scan magnitudes. Inadequate scanning resulted in blind-side detection failures, which might place HH drivers at increased risk for collisions at intersections. Scanning training tailored to specific problem areas identified in this study might be beneficial.},
	keywords = {Accidents, Traffic, Automobile Driving, Computer Simulation, Female, Follow-Up Studies, Hemianopsia, Humans, Male, Middle Aged, Visual Fields, Visual Perception},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12748},
	author = {Bowers, Alex R and Ananyev, Egor and Mandel, Aaron J and Goldstein, Robert B and Peli, Eli}
}
@article {1364585,
	title = {A pilot evaluation of on-road detection performance by drivers with hemianopia using oblique peripheral prisms},
	journal = {Stroke Res Treat},
	volume = {2012},
	year = {2012},
	month = {2012},
	pages = {176806},
	abstract = {Aims. Homonymous hemianopia (HH), a severe visual consequence of stroke, causes difficulties in detecting obstacles on the nonseeing (blind) side. We conducted a pilot study to evaluate the effects of oblique peripheral prisms, a novel development in optical treatments for HH, on detection of unexpected hazards when driving. Methods. Twelve people with complete HH (median 49 years, range 29-68) completed road tests with sham oblique prism glasses (SP) and real oblique prism glasses (RP). A masked evaluator rated driving performance along the 25 km routes on busy streets in Ghent, Belgium. Results. The proportion of satisfactory responses to unexpected hazards on the blind side was higher in the RP than the SP drive (80\% versus 30\%; P = 0.001), but similar for unexpected hazards on the seeing side. Conclusions. These pilot data suggest that oblique peripheral prisms may improve responses of people with HH to blindside hazards when driving and provide the basis for a future, larger-sample clinical trial. Testing responses to unexpected hazards in areas of heavy vehicle and pedestrian traffic appears promising as a real-world outcome measure for future evaluations of HH rehabilitation interventions aimed at improving detection when driving.},
	issn = {2042-0056},
	doi = {10.1155/2012/176806},
	author = {Bowers, Alex R and Tant, Mark and Peli, Eli}
}
@article {1351139,
	title = {Randomized crossover clinical trial of real and sham peripheral prism glasses for hemianopia},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {214-22},
	abstract = {IMPORTANCE: There is a major lack of randomized controlled clinical trials evaluating the efficacy of prismatic treatments for hemianopia. Evidence for their effectiveness is mostly based on anecdotal case reports and open-label evaluations without a control condition. OBJECTIVE: To evaluate the efficacy of real relative to sham peripheral prism glasses for patients with complete homonymous hemianopia. DESIGN, SETTING, AND PARTICIPANTS: Double-masked, randomized crossover trial at 13 study sites, including the Peli laboratory at Schepens Eye Research Institute, 11 vision rehabilitation clinics in the United States, and 1 in the United Kingdom. Patients were 18 years or older with complete homonymous hemianopia for at least 3 months and without visual neglect or significant cognitive decline. INTERVENTION: Patients were allocated by minimization into 2 groups. One group received real (57-prism diopter) oblique and sham (\&lt;5-prism diopter) horizontal prisms; the other received real horizontal and sham oblique, in counterbalanced order. Each crossover period was 4 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the overall difference, across the 2 periods of the crossover, between the proportion of participants who wanted to continue with (said yes to) real prisms and the proportion who said yes to sham prisms. The secondary outcome was the difference in perceived mobility improvement between real and sham prisms. RESULTS: Of 73 patients randomized, 61 completed the crossover. A significantly higher proportion said yes to real than sham prisms (64\% vs 36\%; odds ratio, 5.3; 95\% CI, 1.8-21.0). Participants who continued wear after 6 months reported greater improvement in mobility with real than sham prisms at crossover end (P = .002); participants who discontinued wear reported no difference. CONCLUSIONS AND RELEVANCE: Real peripheral prism glasses were more helpful for obstacle avoidance when walking than sham glasses, with no differences between the horizontal and oblique designs. Peripheral prism glasses provide a simple and inexpensive mobility rehabilitation intervention for hemianopia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00494676.},
	keywords = {Activities of Daily Living, Adolescent, Adult, Aged, Aged, 80 and over, Cross-Over Studies, Double-Blind Method, Eyeglasses, Female, Hemianopsia, Humans, Male, Middle Aged, Patient Satisfaction, Placebos, Prosthesis Design, Surveys and Questionnaires, Treatment Outcome, Vision, Binocular, Visual Fields, Young Adult},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.5636},
	author = {Bowers, Alex R and Keeney, Karen and Peli, Eli}
}
@article {1363249,
	title = {Can we improve clinical prediction of at-risk older drivers?},
	journal = {Accid Anal Prev},
	volume = {59},
	year = {2013},
	month = {2013 Oct},
	pages = {537-47},
	abstract = {OBJECTIVES: To conduct a pilot study to evaluate the predictive value of the Montreal Cognitive Assessment test (MoCA) and a brief test of multiple object tracking (MOT) relative to other tests of cognition and attention in identifying at-risk older drivers, and to determine which combination of tests provided the best overall prediction. METHODS: Forty-seven currently licensed drivers (58-95 years), primarily from a clinical driving evaluation program, participated. Their performance was measured on: (1) a screening test battery, comprising MoCA, MOT, Mini-Mental State Examination (MMSE), Trail-Making Test, visual acuity, contrast sensitivity, and Useful Field of View (UFOV) and (2) a standardized road test. RESULTS: Eighteen participants were rated at-risk on the road test. UFOV subtest 2 was the best single predictor with an area under the curve (AUC) of .84. Neither MoCA nor MOT was a better predictor of the at-risk outcome than either MMSE or UFOV, respectively. The best four-test combination (MMSE, UFOV subtest 2, visual acuity and contrast sensitivity) was able to identify at-risk drivers with 95\% specificity and 80\% sensitivity (.91 AUC). CONCLUSIONS: Although the best four-test combination was much better than a single test in identifying at-risk drivers, there is still much work to do in this field to establish test batteries that have both high sensitivity and specificity.},
	keywords = {Accidents, Traffic, Aged, Aged, 80 and over, Attention, Automobile Driver Examination, Automobile Driving, Cognition, Contrast Sensitivity, Decision Support Techniques, Female, Humans, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Pilot Projects, Predictive Value of Tests, Risk Assessment, Trail Making Test, Visual Acuity, Visual Field Tests},
	issn = {1879-2057},
	doi = {10.1016/j.aap.2013.06.037},
	author = {Bowers, Alex R and Anastasio, R Julius and Sheldon, Sarah S and O{\textquoteright}Connor, Margaret G and Hollis, Ann M and Howe, Piers D and Horowitz, Todd S}
}
@article {1773481,
	title = {2021 Survey of Keratoplasty Postoperative Steroid Management},
	journal = {Cornea},
	volume = {42},
	number = {10},
	year = {2023},
	month = {2023 Oct 01},
	pages = {1268-1273},
	abstract = {PURPOSE: The aim of the study is to investigate US-based ophthalmologists{\textquoteright} preferred corneal transplant techniques and postoperative steroid regimen. METHODS: Ophthalmologists attending the 2021 Cornea and Eye Banking Forum and/or Cornea Subspecialty Day were surveyed in person. RESULTS: Ninety-two ophthalmologists with a median of 13 years (range of 1-35; mean of 14.5; {\textpm}9.05 mean {\textpm} SD) of experience as attending clinicians were surveyed. One hundred percent of the surgeons performed penetrating keratoplasty, which was followed by 96.7\% for Descemet stripping endothelial keratoplasty, 90.2\% for Descemet membrane endothelial keratoplasty, and 72.8\% for deep anterior lamellar keratoplasty. Prednisolone 1\% for postoperative care was the preferred choice across all surveyed keratoplasty techniques and postsurgery time intervals. All surgeons reported steroid administration frequency of 4 times a day in the first month and once a day after 12 months postkeratoplasty. To manage ocular hypertension after corneal transplantation, the leading approach was adding a glaucoma medication (44.6\%), and beta-adrenergic antagonists were ranked as the most preferred choice by 59 (66.3\%) of the respondents. For graft rejection after corneal transplantation, topical steroids (79.8\%) were the initial treatment of choice with hourly administration being the most common frequency prescribed (87.4\%). Most surgeons either agreed or strongly agreed (78.4\%) that a randomized clinical trial evaluating the safety and efficacy of different steroid regimens after corneal transplantation would influence their clinical decision making. CONCLUSIONS: Prednisolone remains the predominantly used steroid across different keratoplasties. Steroid regimens are similar for non-high-risk penetrating keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty, and deep anterior lamellar keratoplasty. To treat graft rejection, surgeons tend to initially add a glaucoma medication than to reduce the potency or frequency of the steroid.},
	keywords = {Corneal Diseases, Corneal Transplantation, Descemet Stripping Endothelial Keratoplasty, Glaucoma, Humans, Keratoplasty, Penetrating, Prednisolone, Steroids, Surveys and Questionnaires},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003174},
	author = {Boychev, Nikolay and De Arrigunaga, Sofia and Zhao, Yan and Ciolino, Joseph B}
}
@article {416921,
	title = {Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate 0.5\% Versus Cyclosporine-A 0.05\% for Treatment of Dry Eye Syndrome Following Hematopoietic Stem Cell Transplantation.},
	journal = {Cornea},
	volume = {34},
	number = {7},
	year = {2015},
	month = {2015 Jul},
	pages = {725-32},
	abstract = {PURPOSE: To evaluate the safety and efficacy of topical loteprednol etabonate (LE) 0.5\% compared with cyclosporine A (CsA) 0.05\% for the prophylaxis and treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation (HSCT). METHODS: Seventy-five patients were randomized to LE (n = 76 eyes of 38 patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score (Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT. RESULTS: There were no differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41; log-rank test) between the 2 treatment arms during the course of the study. Among eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90\% rate of DES development in cyclosporine-treated eyes and a 79\% rate of DES development in LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with DES at enrollment demonstrated a 38\% rate of disease progression among cyclosporine-treated eyes and a 26\% rate of disease progression among loteprednol-treated eyes by 12 months. No patient in either group had an elevation of 10 mm Hg or greater from baseline at any study visit, and no patients had their treatment discontinued for elevation in intraocular pressure. CONCLUSIONS: Pre-HSCT initiation of LE 0.5\% appears to be safe and may be as effective as CsA 0.5\% for the treatment and prophylaxis of DES following HSCT.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000436},
	author = {Boynton, Grace E and Raoof, Duna and Niziol, Leslie M and Hussain, Munira and Mian, Shahzad I}
}
@article {1424796,
	title = {Dry eye disease ranking among common reasons for seeking eye care in a large US claims database},
	journal = {Clin Ophthalmol},
	volume = {13},
	year = {2019},
	month = {2019},
	pages = {225-232},
	abstract = {Objectives: Dry eye disease (DED) is a complex multifactorial condition of the ocular surface characterized by symptoms of ocular discomfort, irritation, and visual disturbance. Data previously reported from this study showed an increase in prevalence and incidence of DED with age and over time. The objective of this study was to compare the ranking of DED prevalence among other ocular conditions that led patients to seek eye care. Methods: In this population-based study using the US Department of Defense Military Health System claims database of \&gt;9.7 million beneficiaries, indicators of DED and other ocular conditions were analyzed over time. The overall prevalence (2003-2015) and annual incidence (2008-2012) of DED and other ocular conditions were estimated using an algorithm based on two independent indicators derived from selected diagnostic and procedure codes and prescriptions for cyclosporine ophthalmic emulsion for DED and diagnostic codes for the indicators of other common ocular conditions. Results: In 2003-2015, the most common ocular conditions were disorders of refraction and accommodation (25.84\%), cataracts (17.14\%), glaucoma (7.27\%), disorders of the conjunctiva (6.76\%), other retinal disorders (5.94\%), and DED (5.28\%). DED was the fifth most prevalent ocular condition in women (7.78\%) and ninth most prevalent in men (2.96\%). In 2012, DED had the third highest annual incidence (0.87\%), behind disorders of refraction/accommodation (1.87\%) and cataracts (1.50\%). Conclusion: This study provided further epidemiologic evidence for DED as a commonly occurring condition that drives patients to seek treatment.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S188314},
	author = {Bradley, John L and Stillman, Ipek {\"O}zer and Pivneva, Irina and Guerin, Annie and Evans, Amber M and Dana, Reza}
}
@article {1586146,
	title = {Epidemiology of Scleritis in the United Kingdom From 1997 to 2018: Population-Based Analysis of 11 Million Patients and Association Between Scleritis and Infectious and Immune-Mediated Inflammatory Disease},
	journal = {Arthritis Rheumatol},
	volume = {73},
	number = {7},
	year = {2021},
	month = {2021 07},
	pages = {1267-1276},
	abstract = {OBJECTIVE: To estimate 22-year trends in the prevalence and incidence of scleritis, and the associations of scleritis with infectious and immune-mediated inflammatory diseases (I-IMIDs) in the UK. METHODS: The retrospective cross-sectional and population cohort study (1997-2018) included 10,939,823 patients (2,946 incident scleritis cases) in The Health Improvement Network, a nationally representative primary care records database. The case-control and matched cohort study (1995-2019) included 3,005 incident scleritis cases and 12,020 control patients matched by age, sex, region, and Townsend deprivation index. Data were analyzed using multivariable Poisson regression, multivariable logistic regression, and Cox proportional hazards multivariable models adjusted for age, sex, Townsend deprivation index, race/ethnicity, smoking status, nation within the UK, and body mass index. Incidence rate ratios (IRRs) and 95\% confidence intervals (95\% CIs) were calculated. RESULTS: Scleritis incidence rates per 100,000 person-years declined from 4.23 (95\% CI 2.16-6.31) to 2.79 (95\% CI 2.19-3.39) between 1997 and 2018. The prevalence of scleritis per 100,000 person-years was 93.62 (95\% CI 90.17-97.07) in 2018 (61,650 UK patients). Among 2,946 patients with incident scleritis, 1,831 (62.2\%) were female, the mean {\textpm} SD age was 44.9 {\textpm} 17.6 years (range 1-93), and 1,257 (88.8\%) were White. Higher risk of incident scleritis was associated with female sex (adjusted IRR 1.53 [95\% CI 1.43-1.66], P \&lt; 0.001), Black race/ethnicity (adjusted IRR 1.52 [95\% CI 1.14-2.01], P = 0.004 compared to White race/ethnicity), or South Asian race/ethnicity (adjusted IRR 1.50 [95\% CI 1.19-1.90], P \&lt; 0.001 compared to White race/ethnicity), and older age (peak adjusted IRR 4.95 [95\% CI 3.99-6.14], P \&lt; 0.001 for patients ages 51-60 years versus those ages <=10 years). Compared to controls, scleritis patients had a 2-fold increased risk of a prior I-IMID diagnosis (17 I-IMIDs, P \&lt; 0.001) and significantly increased risk of subsequent diagnosis (13 I-IMIDs). The I-IMIDs most strongly associated with scleritis included granulomatosis with polyangiitis, Beh{\c c}et{\textquoteright}s disease, and Sj{\"o}gren{\textquoteright}s syndrome. CONCLUSION: From 1997 through 2018, the UK incidence of scleritis declined from 4.23 to 2.79/100,000 person-years. Incident scleritis was associated with 19 I-IMIDs, providing data for rational investigation and cross-specialty engagement.},
	issn = {2326-5205},
	doi = {10.1002/art.41709},
	author = {Braithwaite, Tasanee and Adderley, Nicola J and Subramanian, Anuradhaa and Galloway, James and Kempen, John H and Gokhale, Krishna and Cope, Andrew P and Dick, Andrew D and Nirantharakumar, Krishnarajah and Denniston, Alastair K}
}
@article {1698346,
	title = {Archetypal analysis of longitudinal visual fields for idiopathic intracranial hypertension patients presenting in a clinic setting},
	journal = {PLOS Digit Health},
	volume = {2},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {e0000240},
	abstract = {We previously applied archetypal analysis (AA) using visual fields (VF) from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) to derive a model, which quantified patterns (or archetypes [ATs] of VF loss), anticipated recovery, and identified residual VF deficits. We hypothesized that AA could produce similar results using IIH VFs collected in clinical practice. We applied AA to 803 VFs from 235 eyes with IIH from an outpatient neuro-ophthalmology clinic and created a clinic-derived model of ATs, with the relative weight (RW) and average total deviation (TD) for each AT. We also created a combined-derived model from an input dataset containing the clinic VFs and 2862 VFs from the IIHTT. We used both models to decompose clinic VF into ATs of varying percent weight (PW), correlated presentation AT PW with mean deviation (MD), and evaluated final visit VFs considered "normal" by MD >= -2.00 dB for residual abnormal ATs. The 14-AT clinic-derived and combined-derived models revealed similar patterns of VF loss previously identified in the IIHTT model. AT1 (a normal pattern) was most prevalent in both models (RW = 51.8\% for clinic-derived; 35.4\% for combined-derived). Presentation AT1 PW correlated with final visit MD (r = 0.82, p \&lt; 0.001 for the clinic-derived model; r = 0.59, p \&lt; 0.001 for the combined-derived model). Both models showed ATs with similar patterns of regional VF loss. The most common patterns of VF loss in "normal" final visit VFs using each model were clinic-derived AT2 (mild global depression with enlarged blind spot; 44/125 VFs; 34\%) and combined-derived AT2 (near-normal; 93/149 VFs; 62\%). AA provides quantitative values for IIH-related patterns of VF loss that can be used to monitor VF changes in a clinic setting. Presentation AT1 PW is associated with the degree of VF recovery. AA identifies residual VF deficits not otherwise indicated by MD.},
	issn = {2767-3170},
	doi = {10.1371/journal.pdig.0000240},
	author = {Branco, Joseph and Tobias Elze and Wang, Jui-Kai and Pasquale, Louis R and K Garvin, Mona and Kardon, Randy and Kupersmith, Mark J}
}
@article {1798316,
	title = {Evaluating Visual Acuity in the American Academy of Ophthalmology IRIS{\textregistered} Registry},
	journal = {Ophthalmol Sci},
	volume = {4},
	number = {1},
	year = {2024},
	month = {2024 Jan-Feb},
	pages = {100352},
	abstract = {OBJECTIVE: To describe visual acuity data representation in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry and present a data-cleaning strategy.

DESIGN: Reliability and validity study.

PARTICIPANTS: Patients with visual acuity records from 2018 in the IRIS Registry.

METHODS: Visual acuity measurements and metadata were identified and characterized from 2018 IRIS Registry records. Metadata, including laterality, assessment method (distance, near, and unspecified), correction (corrected, uncorrected, and unspecified), and flags for refraction or pinhole assessment were compared between Rome (frozen April 20, 2020) and Chicago (frozen December 24, 2021) versions. We developed a data-cleaning strategy to infer patients{\textquoteright} corrected distance visual acuity in their better-seeing eye.

MAIN OUTCOME MEASURES: Visual acuity data characteristics in the IRIS Registry.

RESULTS: The IRIS Registry Chicago data set contains 168 920 049 visual acuity records among 23 001 531 unique patients and 49 968 974 unique patient visit dates in 2018. Visual acuity records were associated with refraction in 5.3\% of cases, and with pinhole in 11.0\%. Mean (standard deviation) of all measurements was 0.26 (0.41) logarithm of the minimum angle of resolution (logMAR), with a range of~- 0.3 to 4.0 A plurality of visual acuity records were labeled corrected (corrected visual acuity [CVA], 39.1\%), followed by unspecified (37.6\%) and uncorrected (uncorrected visual acuity [UCVA], 23.4\%). Corrected visual acuity measurements were paradoxically worse than same day UCVA 15\% of the time. In aggregate, mean and median values were similar for CVA and unspecified visual acuity. Most visual acuity measurements were at distance (59.8\%, vs. 32.1\% unspecified and 8.2\% near). Rome contained more duplicate visual acuity records than Chicago (10.8\% vs. 1.4\%). Near visual acuity was classified with Jaeger notation and (in Chicago only) also assigned logMAR values by Verana Health. LogMAR values for hand motion and light perception visual acuity were lower in Chicago than in Rome. The impact of data entry errors or outliers on analyses may be reduced by filtering and averaging visual acuity per eye over time.

CONCLUSIONS: The IRIS Registry includes similar visual acuity metadata in Rome and Chicago. Although fewer duplicate records were found in Chicago, both versions include duplicate and atypical measurements (i.e., CVA worse than UCVA on the same day). Analyses may benefit from using algorithms to filter outliers and average visual acuity measurements over time.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found found in the Footnotes and Disclosures at the end of this article.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100352},
	author = {Brant, Arthur and Kolomeyer, Natasha and Goldberg, Jeffrey L and Haller, Julia and Lee, Cecilia S and Lee, Aaron Y and Lorch, Alice C and Miller, Joan W and Hyman, Leslie and Pershing, Suzann}
}
@article {1709776,
	title = {United States Population Disparities in Ophthalmic Care: Blindness and Visual Impairment in the IRIS{\textregistered} Registry (Intelligent Research in Sight)},
	journal = {Ophthalmology},
	volume = {130},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1121-1137},
	abstract = {PURPOSE: To evaluate associations of patient characteristics with United States eye care use and likelihood of blindness. DESIGN: Retrospective observational study. PARTICIPANTS: Patients (19 546 016) with 2018 visual acuity (VA) records in the American Academy of Ophthalmology{\textquoteright}s IRIS{\textregistered} Registry (Intelligent Research in Sight). METHODS: Legal blindness (20/200 or worse) and visual impairment (VI; worse than 20/40) were identified from corrected distance acuity in the better-seeing eye and stratified by patient characteristics. Multivariable logistic regressions evaluated associations with blindness and VI. Blindness was mapped by state and compared with population characteristics. Eye care use was analyzed by comparing population demographics with United States Census estimates and proportional demographic representation among blind patients versus a nationally representative US population sample (National Health and Nutritional Examination Survey [NHANES]). MAIN OUTCOME MEASURES: Prevalence and odds ratios for VI and blindness; proportional representation in the IRIS{\textregistered} Registry, Census, and NHANES by patient demographics. RESULTS: Visual impairment was present in 6.98\% (n\&nbsp;= 1 364 935) and blindness in 0.98\% (n\&nbsp;= 190 817) of IRIS patients. Adjusted odds of blindness were highest among patients >= 85 years old (odds ratio [OR], 11.85; 95\% confidence interval [CI], 10.33-13.59 vs. those 0-17 years old). Blindness also was associated positively with rural location and Medicaid, Medicare, or no\&nbsp;insurance vs. commercial insurance. Hispanic (OR, 1.59; 95\% CI, 1.46-1.74) and Black (OR, 1.73; 95\% CI, 1.63-1.84) patients showed a higher odds of blindness versus White non-Hispanic patients. Proportional representation in IRIS Registry relative to the Census was higher for White than Hispanic (2- to 4-fold) or Black (11\%-85\%) patients (P \&lt; 0.001). Blindness overall was less prevalent in NHANES than IRIS Registry; however, prevalence in adults aged 60+ was lowest among Black participants in the NHANES (0.54\%) and second highest among comparable Black adults in IRIS (1.57\%). CONCLUSIONS: Legal blindness from low VA was present in 0.98\% of IRIS patients and associated with rural location, public or no insurance, and older age. Compared with US Census estimates, minorities may be underrepresented among ophthalmology patients, and compared with NHANES population estimates, Black individuals may be overrepresented among blind IRIS Registry patients. These findings provide a snapshot of US ophthalmic care and highlight the need for initiatives to address disparities in use and blindness. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.06.011},
	author = {Brant, Arthur and Kolomeyer, Natasha and Goldberg, Jeffrey L and Haller, Julia and Lee, Cecilia S and Lee, Aaron Y and Lorch, Alice C and Lum, Flora and Miller, Joan W and Parke, David W and Hyman, Leslie and Pershing, Suzann}
}
@article {913411,
	title = {Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration.},
	journal = {Mol Pharm},
	volume = {13},
	number = {9},
	year = {2016},
	month = {2016 Sep 6},
	pages = {2966-76},
	abstract = {The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 μM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 μM) and ACZ (0.07\%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.},
	issn = {1543-8392},
	doi = {10.1021/acs.molpharmaceut.6b00182},
	author = {Bravo-Osuna, I and Vicario-de-la-Torre, M and Andr{\'e}s-Guerrero, V and S{\'a}nchez-Nieves, J and Guzm{\'a}n-Navarro, M and de la Mata, F J and G{\'o}mez, R and de Las Heras, B and Arg{\"u}eso, P and Ponchel, G and Herrero-Vanrell, R and Molina-Mart{\'\i}nez, I T}
}
@article {1538333,
	title = {Lamina Cribrosa Capillaries Straighten as Intraocular Pressure Increases},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {12},
	year = {2020},
	month = {2020 Oct 01},
	pages = {2},
	abstract = {Purpose: The purpose of this study was to visualize the lamina cribrosa (LC) capillaries and collagenous beams, measure capillary tortuosity (path length over straight end-to-end length), and determine if capillary tortuosity changes when intraocular pressure (IOP) increases. Methods: Within 8 hours of sacrifice, 3 pig heads were cannulated via the external ophthalmic artery, perfused with PBS to remove blood, and then perfused with a fluorescent dye to label the capillaries. The posterior pole of each eye was mounted in a custom-made inflation chamber for control of IOP with simultaneous imaging. Capillaries and collagen beams were visualized with structured light illumination enhanced imaging at IOPs from 5 to 50 mm Hg at each 5 mm Hg increment. Capillary tortuosity was measured from the images and paired two-sample t-tests were used to assess for significant changes in relation to changes in IOP. Results: Capillaries were highly tortuous at 15 mm Hg (up to 1.45). In all but one eye, tortuosity decreased significantly as IOP increased from 15 to 25 mm Hg (P \&lt; 0.01), and tortuosity decreased significantly in every eye as IOP increased from 15 to 40 mm Hg (P \&lt; 0.01). In only 16\% of capillaries, tortuosity increased with elevated IOP. Capillaries had a surprisingly different topology from the collagen beams. Conclusions: Although high capillary tortuosity is sometimes regarded as potentially problematic because it can reduce blood flow, LC capillary tortuosity may provide slack that mitigates against reduced flow and structural damage caused by excessive stretch under elevated IOP. We speculate that low capillary tortuosity could be a risk factor for damage under high IOP.},
	issn = {1552-5783},
	doi = {10.1167/iovs.61.12.2},
	author = {Brazile, Bryn L and Yang, Bin and Waxman, Susannah and Lam, Po and Voorhees, Andrew P and Hua, Yi and Loewen, Ralitsa T and Loewen, Nils A and Rizzo, Joseph F and Jakobs, Tatjana and Sigal, Ian A}
}
@article {1586148,
	title = {Frequency of Urgent or Emergent Vitreoretinal Surgical Procedures in the United States During the COVID-19 Pandemic},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {4},
	year = {2021},
	month = {2021 04 01},
	pages = {456-463},
	abstract = {Importance: The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time. Objective: To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic. Design, Setting, and Participants: Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders. Main Outcomes and Measures: Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic. Results: A total of 526 536 CPT codes were ascertained: 483 313 injections, 19 257 lasers or cryotherapy, 14 949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6\% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95\% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6\% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95\% CI, -6.8 to -3.3 procedures; P \&lt; .001), for RD repairs, with a maximal 59.4\% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95\% CI, -2.7 to -1.4 repairs; P \&lt; .001), and for other vitrectomies, with a maximal 84.3\% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95\% CI, -3.3 to -1.8 other vitrectomies; P \&lt; .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment. Conclusions and Relevance: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic{\textquoteright}s initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.0036},
	author = {Breazzano, Mark P and Nair, Archana A and Arevalo, J Fernando and Barakat, Mark R and Berrocal, Audina M and Chang, Jonathan S and Andrew Chen and Eliott, Dean and Garg, Sunir J and Ghadiali, Quraish and Gong, Dan and Grewal, Dilraj S and Handa, James T and Henderson, Matthew and Leiderman, Yannek I and Leng, Theodore and Mannina, Amar and Mendel, Thomas A and Mustafi, Debarshi and de Koo, Lisa C Olmos and Patel, Shriji N and Patel, Tapan P and Prenner, Jonathan and Richards, Paige and Singh, Rishi P and Wykoff, Charles C and Yannuzzi, Nicolas A and Yu, Hannah and Modi, Yasha S and Chang, Stanley}
}
@article {1608573,
	title = {Conjunctival Melanocytic Lesions},
	journal = {Arch Pathol Lab Med},
	volume = {146},
	number = {5},
	year = {2022},
	month = {2022 05 01},
	pages = {632-646},
	abstract = {CONTEXT.{\textemdash}: Conjunctival melanocytic lesions consist of a variety of neoplastic and nonneoplastic conditions. These include benign processes such as primary intraepithelial hypermelanosis and melanocytic hyperplasia, secondary forms of intraepithelial hypermelanosis and melanocytic hyperplasia, melanocytic nevi, melanocytic proliferations with malignant potential, and melanoma. OBJECTIVE.{\textemdash}: To provide a concise yet comprehensive resource regarding the histopathologic diagnosis of conjunctival melanocytic lesions. We aim to detail and clarify the numerous classification schemes that exist for junctional melanocytic proliferations of the conjunctiva (known as primary acquired melanosis or PAM; also termed conjunctival melanocytic intraepithelial neoplasia or C-MIN). Although not uniformly adopted, C-MIN is classified by using a numeric system based on a defined set of criteria. A less complex scheme (conjunctival melanocytic intraepithelial lesion or CMIL) has recently been proposed by the World Health Organization. Additionally, we aim to update the reader regarding molecular features and prognostic indicators. DATA SOURCES.{\textemdash}: Peer-reviewed literature and archived cases for illustration. CONCLUSIONS.{\textemdash}: Accurate histologic classification is essential, as PAM/C-MIN/CMILs that have a significant potential to progress to invasive melanoma may be clinically indistinguishable from low-risk lesions. Conjunctival melanoma (CM) more closely resembles cutaneous melanoma in terms of its pathogenesis and molecular features, compared to melanoma arising at other mucosal sites or to uveal melanoma. Depth of invasion and ulceration status, among other factors, have emerged as important prognostic indicators in CM. Sentinel lymph node biopsy may provide further prognostic information. Lastly, integration of pathologic and clinical findings is essential at this anatomically sensitive location to determine appropriate clinical management.},
	keywords = {Conjunctival Neoplasms, Humans, Hyperpigmentation, Hyperplasia, Melanoma, Skin Neoplasms},
	issn = {1543-2165},
	doi = {10.5858/arpa.2021-0006-RA},
	author = {Bresler, Scott C and Simon, Caroline and Shields, Carol L and McHugh, Jonathan B and Stagner, Anna M and Patel, Rajiv M}
}
@article {1445320,
	title = {Association Between Change in Visual Acuity and Change in Central Subfield Thickness During Treatment of Diabetic Macular Edema in Participants Randomized to Aflibercept, Bevacizumab, or Ranibizumab: A Post Hoc Analysis of the Protocol T Randomized Clinic},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Jun 27},
	abstract = {Importance: The determination of optical coherence tomography (OCT) central subfield thickness (CST) is an objective measure, and visual acuity (VA) is a subjective measure. Therefore, using OCT CST changes as a surrogate for VA changes in diabetic macular edema seems reasonable. However, studies suggest that change in OCT CST following anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema is correlated with changes in VA but varies substantially among individuals, and so may not be a good surrogate for changes in VA. Objective: To determine associations between changes in VA and changes in OCT CST across 3 anti-VEGF agents (aflibercept, bevacizumab, or ranibizumab) used in a randomized clinical trial for diabetic macular edema. Design, Setting, and Participants: Post hoc analyses were conducted of DRCR Retina Network Protocol T among 652 of 660 participants (98.8\%) meeting inclusion criteria for this investigation. The study was conducted between August 22, 2012, and September 23, 2015. The post hoc data collection and analysis were performed from May 29 to July 11, 2018. Interventions: Six monthly intravitreous anti-VEGF injections (unless success was achieved after 3-5 months) were administered; subsequent injections or focal/grid laser photocoagulation treatments were given as needed per protocol to achieve stability. Main Outcomes and Measures: Association between changes in VA letter score with changes in CST at 12, 52, and 104 weeks after randomization to aflibercept, bevacizumab, or ranibizumab. Results: Of the 652 participants, 304 were women (46.6\%); median age was 61 years (interquartile range, 54-67 years). The correlation between CST and VA at the follow-up visits was 0.24 (95\% CI, 0.16-0.31) in 616 patients at 12 weeks, 0.31 (95\% CI, 0.24-0.38) in 609 patients at 52 weeks, and 0.23 (95\% CI, 0.15-0.31) in 566 patients at 104 weeks. The correlation coefficients of change in VA vs change in OCT CST for these time intervals were 0.36 (95\% CI, 0.29-0.43) at 12 weeks, 0.36 (95\% CI, 0.29-0.43) at 52 weeks, and 0.33 (95\% CI, 0.26-0.41) at 104 weeks. Conclusions and Relevance: Changes in CST appear to account for only a small proportion of the total variation in changes in VA. These findings do not support using changes in OCT CST as a surrogate for changes in VA in phase 3 clinical trials evaluating anti-VEGF for diabetic macular edema or as a guide to inform the physician or patient about changes in VA after anti-VEGF treatment. Trial Registration: ClinicalTrials.gov identifier: NCT01627249.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.1963},
	author = {Bressler, Neil M and Odia, Isoken and Maguire, Maureen and Glassman, Adam R and Jampol, Lee M and MacCumber, Mathew W and Shah, Chirag and Rosberger, Daniel and Sun, Jennifer K and DRCR Retina Network}
}
@article {1363250,
	title = {Green or yellow laser treatment for diabetic macular edema: exploratory assessment within the Diabetic Retinopathy Clinical Research Network},
	journal = {Retina},
	volume = {33},
	number = {10},
	year = {2013},
	month = {2013 Nov-Dec},
	pages = {2080-8},
	abstract = {PURPOSE: Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomical endpoints in eyes with diabetic macular edema. METHODS: Data from two randomized clinical trials were evaluated for differences in visual acuity and optical coherence tomography parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. RESULTS: In the sham injection + prompt laser group, the mean visual acuity letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4 {\textpm} 14 and +5.1 {\textpm} 13 at the 52-week visit (P = 0.06) and +2.4 {\textpm} 15 and +6.0 {\textpm} 13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in optical coherence tomography thickness. When comparing wavelength groups in the ranibizumab + prompt laser and prompt laser-only groups, meaningful differences in visual acuity and optical coherence tomography thickness were not detected at 1 year or 2 years. CONCLUSION: A trend toward improved vision outcome with yellow laser observed in one trial was not corroborated by anatomical outcomes or by the other trial. In this study, without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other.},
	keywords = {Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Combined Modality Therapy, Diabetic Retinopathy, Glucocorticoids, Humans, Laser Coagulation, Lasers, Dye, Macular Edema, Ranibizumab, Triamcinolone Acetonide, Visual Acuity},
	issn = {1539-2864},
	doi = {10.1097/IAE.0b013e318295f744},
	author = {Bressler, Susan B and Almukhtar, Talat and Aiello, Lloyd P and Bressler, Neil M and Ferris, Frederick L and Glassman, Adam R and Greven, Craig M and Diabetic Retinopathy Clinical Research Network}
}
@article {1417550,
	title = {Factors Associated With Visual Acuity and Central Subfield Thickness Changes When Treating Diabetic Macular Edema With Anti-Vascular Endothelial Growth Factor Therapy: An Exploratory Analysis of the Protocol T Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Jan 24},
	abstract = {Importance: Identifying the factors that are associated with the magnitude of treatment benefits from anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) may help refine treatment expectations. Objective: To identify the baseline factors that are associated with vision and anatomic outcomes when managing DME with anti-VEGF and determine if there are interactions between factors and the agent administered. Design, Setting, and Participants: This post hoc analysis of data from the Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial , Protocol T, was conducted between December 2016 and December 2017. Between August 22, 2012, and August 28, 2013, 660 participants were enrolled with central-involved DME and vision impairment (approximate Snellen equivalent, 20/32-20/320). Interventions: Repeated 0.05-mL intravitreous injections of 2.0-mg aflibercept (201 eyes), 1.25-mg bevacizumab (185 eyes), or 0.3-mg ranibizumab (192 eyes) per protocol. Main Outcomes and Measures: Change in visual acuity (VA) and optical coherence tomography (OCT) central subfield thickness at 2 years and change in VA over 2 years (area under the curve [AUC]). Results: Among 578 participants, the median age (interquartile range) was 61 (54-67) years. Across anti-VEGF treatment groups, each baseline factor was associated with mean improvement in VA and a reduction in central DME compared with the baseline. For every decade of participant age, the mean VA improvement was reduced by 2.1 letters (95\% CI, -3.0 to -1.2; P \&lt; .001) in the VA and 1.9 letters (95\% CI, -2.4 to -1.3; P \&lt; .001) in the VA AUC analyses. For each 1\% increase in hemoglobin A1c levels, VA improvement was reduced by 1 letter in the VA (95\% CI, -1.5 to -0.5; P \&lt; .001) and 0.5 letters (95\% CI, -0.9 to -0.2; P \&lt; .001) in the VA AUC analyses. Eyes with no prior panretinal photocoagulation (PRP) and less than severe nonproliferative diabetic retinopathy had an approximately 3-letter improvement in the VA (95\% CI, 0.9-5.4; P = .007) and VA AUC (95\% CI, 1.3-4.2; P \&lt; .001) analyses compared with eyes with prior PRP. On average, African American participants had greater reductions in central subfield thickness compared with eyes of white participants (-27.3 μm, P = .01), as did eyes with central subretinal fluid compared with eyes without this OCT feature (-22.9 μm, P = .01). There were no interactions between the predictive factors and the specific anti-VEGF agent that was administered for any VA or OCT outcome. Conclusions and Relevance: Lower hemoglobin A1c levels were associated with the magnitude of vision improvement following anti-VEGF therapy, providing further evidence to encourage glycemic control among persons with diabetes. Younger patients and those without prior PRP might expect greater improvement in VA than older patients or those with prior PRP.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.6786},
	author = {Bressler, Susan B and Odia, Isoken and Maguire, Maureen G and Dhoot, Dilsher S and Glassman, Adam R and Jampol, Lee M and Marcus, Dennis M and Solomon, Sharon D and Sun, Jennifer K and Diabetic Retinopathy Clinical Research Network}
}
@article {1328875,
	title = {Early Response to Anti-Vascular Endothelial Growth Factor and Two-Year Outcomes Among Eyes With Diabetic Macular Edema in Protocol T},
	journal = {Am J Ophthalmol},
	volume = {195},
	year = {2018},
	month = {2018 Nov},
	pages = {93-100},
	abstract = {PURPOSE: Assess associations of 2-year visual acuity (VA) outcomes with VA and optical coherence tomography central subfield thickness (CST) after 12\&nbsp;weeks of anti-vascular endothelial growth factor treatment for diabetic macular edema in DRCR.net Protocol T. DESIGN: Randomized clinical trial. METHODS: Setting: Multicenter (89\&nbsp;U.S. sites). PATIENT POPULATION: Eyes with VA and CST data from baseline and 12-week visits (616 of 660 eyes randomized [93.3\%]). INTERVENTION: Six monthly injections of 2.0\&nbsp;mg aflibercept, 1.25\&nbsp;mg bevacizumab, or 0.3\&nbsp;mg ranibizumab; subsequent injections and focal/grid laser as needed for stability. MAIN OUTCOME MEASURES: Change in VA from baseline and VA letter score at 2 years. RESULTS: Twelve-week VA response was associated with 2-year change in VA and 2-year VA letter score for each drug (P \&lt; .001) but with substantial individual variability (multivariable R\&nbsp;= 0.38, 0.29, and 0.26 for 2-year change with aflibercept, bevacizumab, and ranibizumab, respectively). Among eyes with less than 5-letter gain at 12\&nbsp;weeks, the percentages of eyes gaining 10 or more letters from baseline at 2 years were 42\% (20 of 48), 31\% (21 of 68), and 47\% (28 of 59), and median 2-year VA was 20/32, 20/32, and 20/25, in the aflibercept, bevacizumab, and ranibizumab groups, respectively. Twelve-week CST response was not strongly associated with 2-year outcomes. CONCLUSIONS: A suboptimal response at 12\&nbsp;weeks did not preclude meaningful vision improvement (ie, >= 10-letter gain) in many eyes at 2 years. Eyes with less than 5-letter gain at 12\&nbsp;weeks often had good VA at 2 years without switching therapies.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.07.030},
	author = {Bressler, Neil M and Beaulieu, Wesley T and Maguire, Maureen G and Glassman, Adam R and Blinder, Kevin J and Bressler, Susan B and Gonzalez, Victor H and Jampol, Lee M and Melia, Michele and Sun, Jennifer K and Wells, John A and Diabetic Retinopathy Clinical Research Network}
}
@article {369006,
	title = {Reproducibility of Optovue RTVue Optical Coherence Tomography Retinal Thickness Measurements and Conversion to Equivalent Zeiss Stratus Metrics in Diabetic Macular Edema.},
	journal = {Transl Vis Sci Technol},
	volume = {4},
	number = {1},
	year = {2015},
	month = {2015 Jan},
	pages = {5},
	abstract = {PURPOSE: To evaluate the reproducibility of central subfield thickness (CST) and volume measurements from optical coherence tomography (OCT) images obtained with Zeiss Stratus and Optovue RTVue, and formulate equations to convert these measurements from RTVue to {\textquoteright}equivalent{\textquoteright} Stratus values. METHODS: Cross-sectional observational study from 309 eyes of 167 participants with diabetes and at least one eye with central-involved diabetic macular edema (DME; Stratus CST >= 250 μm) that underwent two replicate Stratus scans followed by two replicate RTVue scans centered on the fovea. RESULTS: The Bland-Altman coefficient of repeatability for relative change in CST (the degree of change that could be expected from measurement variability) was not significantly different on Stratus and RTVue scans (10\% and 16\%, respectively). The replicate Stratus CST was within 10\% of the initial Stratus measurement 93\% of the time; the CST conversion equation predicted a Stratus value calculated from the observed RTVue value within 10\% of the observed Stratus thickness 91\% of the time. Bland-Altman limit of agreement for relative change in CST between measurements observed on different machines was 23\%, comparing predicted versus actual Stratus measurement. CONCLUSIONS: RTVue thickness reproducibility appears similar to Stratus. Conversion equations to transform RTVue measurements to Stratus-equivalent values within 10\% of the observed Stratus RT are feasible. CST changes greater than 10\% when using the same machine or 20\% when switching from Stratus to RTVue, after conversion to Stratus equivalents, are likely due to a true change beyond measurement error. TRANSLATIONAL RELEVANCE: Conversion equations to translate central retinal thickness measurements between OCT instruments is critical to clinical trials.},
	issn = {2164-2591},
	doi = {10.1167/tvst.4.1.5},
	author = {Bressler, Susan B and Edwards, Allison R and Andreoli, Christopher M and Edwards, Paul Andrew and Glassman, Adam R and Jaffe, Glenn J and Melia, Michele and Sun, Jennifer K and for the Diabetic Retinopathy Clinical Research Network/Writing Committee}
}
@article {1466895,
	title = {ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND RISK OF TRACTION RETINAL DETACHMENT IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY: Pooled Analysis of Five DRCR Retina Network Randomized Clinical Trials},
	journal = {Retina},
	volume = {40},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {1021-1028},
	abstract = {PURPOSE: To investigate whether anti-vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR. METHODS: Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level >=61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization. RESULTS: The 1-year cumulative probability of TRD was 6.8\% (95\% confidence interval: 4.6\%-9.9\%, 25 events) in control-group eyes and 4.8\% (95\% confidence interval: 3.2\%-7.3\%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95\% confidence interval: 0.54-1.66, P = 0.86]). The cumulative probability of vitrectomy for TRD was 4.4\% (16 events) in control-group eyes and 2.2\% (9 events) in anti-VEGF group eyes (P = 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity. CONCLUSION: These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002633},
	author = {Bressler, Neil M and Beaulieu, Wesley T and Bressler, Susan B and Glassman, Adam R and Melia, B Michele and Jampol, Lee M and Jhaveri, Chirag D and Salehi-Had, Hani and Velez, Gisela and Sun, Jennifer K and DRCR Retina Network}
}
@article {1782256,
	title = {The impact of the COVID-19 pandemic on childhood lead testing and blood lead levels},
	journal = {Acad Pediatr},
	year = {2023},
	month = {2023 Nov 16},
	abstract = {OBJECTIVE: To evaluate the effect of the COVID-19 pandemic on childhood lead testing and blood lead levels METHODS: A retrospective analysis of lead tests and results was performed across three urban medical centers during the pre-COVID-19 (March 10, 2019-March 9, 2020) and COVID-19 (March 10, 2020-March 10, 2022) periods. Interrupted time series analysis with quasi-Poisson regression was used to evaluate changes in lead testing between study periods. The relationship between sociodemographic features with detectable (≧2 {\textmu}g/dL) and elevated (≧3.5 {\textmu}g/dL) blood lead levels (BLLs) was assessed with multivariable logistic regression. RESULTS: Among a total of 16,364 lead tests across 10,362 patients, weekly testing rates significantly decreased during COVID-19 (RR 0.64, 95\% CI 0.53-0.78). Census tracts with the greatest proportion of pre-1950s housing had a stronger association with detectable BLLs during the COVID-19 period (Pre-COVID-19 aOR 1.73, 95\% CI 1.35-2.20; aOR 2.58, 95\% CI 2.13-3.12; Interaction p-value 0.014). When limited to one year following COVID-19 (March 10, 2020-March 10, 2021), the association between both elevated BLLs (Pre-COVID-19: aOR 1.49, 95\% CI 0.87-2.53; COVID-19: aOR 3.51, 95\% CI 1.98-6.25; Interaction p-value 0.032) and detectable BLLs with pre-1950s housing were greater during the COVID-19 period (Pre-COVID-19: aOR 1.73, 95\% CI 1.35-2.20; COVID-19: aOR 2.56, 95\% CI 1.95-3.34; Interaction p-value 0.034). CONCLUSIONS: The COVID-19 pandemic led to a significant reduction in lead surveillance and magnified the effect of known risk factors for lead exposure. Concerted clinical, public health, and community advocacy are needed to address care gaps and excess cases of lead poisoning.},
	issn = {1876-2867},
	doi = {10.1016/j.acap.2023.11.014},
	author = {Brewster, Ryan Cl and Azad, Amee D and Acosta, Keith and Starmer, Amy and Sprecher, Eli and Rea, Corinna and Gray, Kathryn P and Reagan, Shannon and Wilson, Joseph and Bayuh, Frehiwot and Buncher, Noah and Hauptman, Marissa}
}
@article {1586193,
	title = {Uveitis Specialists Harnessing Disruptive Technology during the COVID-19 Pandemic and Beyond},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {296-303},
	abstract = {Spurred by the coronavirus disease pandemic and shortage of eye care providers, telemedicine is transforming the way ophthalmologists care for their patients. Video conferencing, ophthalmic imaging, hybrid visits, intraocular inflammation quantification, and portable technology are evolving areas that may allow more uveitis patients to be evaluated via telemedicine. Despite these promising disruptive technologies, there remain significant technological limitations, legal barriers, variable insurance coverage for virtual visits, and lack of clinical trials for uveitis specialists to embrace telemedicine.},
	keywords = {COVID-19, Delivery of Health Care, Humans, Ophthalmology, SARS-CoV-2, Specialization, Telemedicine, Uveitis},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1896753},
	author = {Brill, Daniel and Papaliodis, George}
}
@article {1402573,
	title = {Glycosylation pathways of human corneal and conjunctival epithelial cell mucins},
	journal = {Carbohydr Res},
	volume = {470},
	year = {2018},
	month = {2018 Dec},
	pages = {50-56},
	abstract = {Mucin glycoproteins on the ocular surface are rich in O-glycans and have important roles in the protection from physical, chemical and microbial impact. In this work, we have cultured human corneal and conjunctival epithelial cells to examine the glycosyltransferase activities that synthesize the O-glycans of mucins. The results indicate that ocular surface epithelial cells have active enzymes that synthesize O-glycans with sialylated core 1, Galβ1-3GalNAcα, and core 2, GlcNAcβ1-6(Galβ1-3)GalNAcα structures which corresponds to previous structural studies. Eye cells also have enzymes that synthesize complex N-glycans that are found on mucins. Results from treatment of eye cells with TNFα suggest that epithelial O-glycosylation changes in a dynamic fashion during inflammatory stimuli of the eye surface.},
	issn = {1873-426X},
	doi = {10.1016/j.carres.2018.10.004},
	author = {Brockhausen, Inka and Elimova, Elena and Woodward, Ashley M and Arg{\"u}eso, Pablo}
}
@article {284021,
	title = {The clinically used photosensitizer Verteporfin (VP) inhibits YAP-TEAD and human retinoblastoma cell growth in vitro without light activation},
	journal = {Exp Eye Res},
	volume = {124},
	year = {2014},
	month = {2014 Jul},
	pages = {67-73},
	abstract = {Verteporfin (VP), a benzoporphyrin derivative, is clinically used in photodynamic therapy for neovascular macular degeneration. Recent studies indicate that VP may inhibit growth of hepatoma cells without photoactivation through inhibition of YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human retinoblastoma cell lines. Verteporfin but not vehicle control inhibited the growth, proliferation and viability of human retinoblastoma cell lines (Y79 and WERI) in a dose-dependent manner and was associated with downregulation of YAP-TEAD associated downstream proto-oncogenes such as c-myc, Axl, and surviving. In addition VP affected signals involved in cell migration and angiogenesis such as CTGF, cyr61, and VEGF-A but was not associated with significant effect on the mTOR/autophagy pathway. Of interest the pluripotency marker Oct4 were downregulated by Verteporfin treatment. Our results indicate that the clinically used photosensitizer VP is a potent inhibitor of cell growth in retinoblastoma cells, disrupting YAP-TEAD signaling and pluripotential marker OCT4. This study highlights for the first time the role of the YAP-TEAD pathway in Retinoblastoma and suggests that VP may be a useful adjuvant therapeutic tool in treating Rb patients.},
	keywords = {Cell Proliferation, Child, Preschool, Dose-Response Relationship, Drug, Follow-Up Studies, Humans, Infant, Infant, Newborn, Photochemotherapy, Photosensitizing Agents, Porphyrins, Retina, Retinal Neoplasms, Retinoblastoma, Tumor Cells, Cultured},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2014.04.011},
	author = {Brodowska, Katarzyna and Al-Moujahed, Ahmad and Marmalidou, Anna and Meyer Zu Horste, Melissa and Cichy, Joanna and Miller, Joan W and Gragoudas, Evangelos and Vavvas, Demetrios G}
}
@article {280846,
	title = {Effects of metformin on retinoblastoma growth in vitro and in vivo.},
	journal = {Int J Oncol},
	volume = {45},
	number = {6},
	year = {2014},
	month = {2014 Dec},
	pages = {2311-24},
	abstract = {Recent studies suggest that the anti-diabetic drug metformin may reduce the risk of cancer and have anti-proliferative effects for some but not all cancers. In this study, we examined the effects of metformin on human retinoblastoma cell proliferation in vitro and in vivo. Two different human retinoblastoma cell lines (Y79, WERI) were treated with metformin in vitro and xenografts of Y79 cells were established in nu/nu immune-deficient mice and used to assess the effects of pharmacological levels of metformin in vivo. Metformin inhibited proliferation of the retinoblastoma cells in vitro. Similar to other studies, high concentrations of metformin (mM) blocked the cell cycle in G0-G1, indicated by a strong decrease of G1 cyclins, especially cyclin D, cyclin-dependent kinases (4 and 6), and flow cytometry assessment of the cell cycle. This was associated with activation of AMPK, inhibition of the mTOR pathways and autophagy marker LC3B. However, metformin failed to suppress growth of xenografted tumors of Y79 human retinoblastoma cells in nu/nu mice, even when treated with a maximally tolerated dose level achieved in human patients. In conclusion, suprapharmacological levels (mM) of metformin, well above those tolerated in vivo, inhibited the proliferation of retinoblastoma cells in vitro. However, physiological levels of metformin, such as seen in the clinical setting, did not affect the growth of retinoblastoma cells in vitro or in vivo. This suggests that the potential beneficial effects of metformin seen in epidemiological studies may be limited to specific tumor types or be related to indirect effects/mechanisms not observed under acute laboratory conditions.},
	issn = {1791-2423},
	doi = {10.3892/ijo.2014.2650},
	author = {Brodowska, Katarzyna and Theodoropoulou, Sofia and Meyer Zu H{\"o}rste, Melissa and Paschalis, Eleftherios I and Takeuchi, Kimio and Scott, Gordon and Ramsey, David J and Kiernan, Elizabeth and Hoang, Mien and Cichy, Joanna and Miller, Joan W and Gragoudas, Evangelos S and Vavvas, Demetrios G}
}
@article {1062811,
	title = {Validation of the Retinal Detachment after Open Globe Injury (RD-OGI) Score as an Effective Tool for Predicting Retinal Detachment},
	journal = {Ophthalmology},
	volume = {124},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {674-678},
	abstract = {
	PURPOSE: The Retinal Detachment after Open Globe Injury (RD-OGI) Score is a clinical prediction model that was developed at the Massachusetts Eye and Ear Infirmary to predict the risk of retinal detachment (RD) after open globe injury (OGI). This study sought to validate the RD-OGI Score in an independent cohort of patients. DESIGN: Retrospective cohort study. PARTICIPANTS: The predictive value of the RD-OGI Score was evaluated by comparing the original RD-OGI Scores of 893 eyes with OGI that presented between 1999 and 2011 (the derivation cohort) with 184 eyes with OGI that presented from January 1, 2012, to January 31, 2014 (the validation cohort). METHODS: Three risk classes (low, moderate, and high) were created and logistic regression was undertaken to evaluate the optimal predictive value of the RD-OGI Score. A Kaplan-Meier survival analysis evaluated survival experience between the risk classes. MAIN OUTCOME MEASURES: Time to RD. RESULTS: At 1 year after OGI, 255 eyes (29\%) in the derivation cohort and 66 eyes (36\%) in the validation cohort were diagnosed with an RD. At 1 year, the low risk class (RD-OGI Scores 0-2) had a 3\% detachment rate in the derivation cohort and a 0\% detachment rate in the validation cohort, the moderate risk class (RD-OGI Scores 2.5-4.5) had a 29\% detachment rate in the derivation cohort and a 35\% detachment rate in the validation cohort, and the high risk class (RD-OGI scores 5-7.5) had a 73\% detachment rate in the derivation cohort and an 86\% detachment rate in the validation cohort. Regression modeling revealed the RD-OGI to be highly discriminative, especially 30 days after injury, with an area under the receiver operating characteristic curve of 0.939 in the validation cohort. Survival experience was significantly different depending upon the risk class (P\&nbsp;\&lt;\&nbsp;0.0001, log-rank chi-square). CONCLUSIONS: The RD-OGI Score can reliably predict the future risk of developing an RD based on clinical variables that are present at the time of the initial evaluation after OGI.

},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.12.032},
	author = {Brodowska, Katarzyna and Stryjewski, Tomasz P and Papavasileiou, Evangelia and Chee, Yewlin E and Eliott, Dean}
}
@article {1580473,
	title = {Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury},
	journal = {Nat Commun},
	volume = {12},
	number = {1},
	year = {2021},
	month = {2021 02 03},
	pages = {781},
	abstract = {After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.},
	keywords = {Animals, Antipsychotic Agents, Clozapine, Dependovirus, Genetic Vectors, Hindlimb, Locomotion, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Spinal Cord, Spinal Cord Injuries},
	issn = {2041-1723},
	doi = {10.1038/s41467-021-20980-4},
	author = {Brommer, Benedikt and He, Miao and Zhang, Zicong and Yang, Zhiyun and Page, Jessica C and Su, Junfeng and Zhang, Yu and Zhu, Junjie and Gouy, Emilia and Tang, Jing and Williams, Philip and Dai, Wei and Wang, Qi and Solinsky, Ryan and Chen, Bo and He, Zhigang}
}
@article {1460369,
	title = {Corrigendum to: TFOS DEWS II pathophysiology report. Ocul Surf (2017)15(3): 438-510},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Aug 08},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.08.007},
	author = {Bron, Anthony J and de Paiva, Cintia S and Chauhan, Sunil K and Bonini, Stefano and Gabison, Eric E and Jain, Sandeep and Knop, Erich and Markoulli, Maria and Ogawa, Yoko and Perez, Victor and Uchino, Yuichi and Yokoi, Norihiko and Zoukhri, Driss and Sullivan, David A}
}
@article {369096,
	title = {Clinical staining of the ocular surface: mechanisms and interpretations.},
	journal = {Prog Retin Eye Res},
	volume = {44},
	year = {2015},
	month = {2015 Jan},
	pages = {36-61},
	abstract = {In this article we review the mechanism of ocular surface staining. Water-soluble dyes are excluded from the normal epithelium by tight junctions, the plasma membranes and the surface glycocalyx. Shed cells can take up dye. A proportion of normal corneas show sparse, scattered time-dependent, punctate fluorescein uptake, which, we hypothesise, is due to a graded loss of the glycocalyx barrier, permitting transcellular entry into pre-shed cells. In pathological staining, there is little evidence of {\textquoteright}micropooling{\textquoteright} at sites of shedding and the term {\textquoteright}punctate erosion{\textquoteright} may be a misnomer. It is more likely that the initial event involves transcellular dye entry and, in addition, diffusion across defective tight junctions. Different dye-staining characteristics probably reflect differences in molecular size and other physical properties of each dye, coupled with differences in visibility under the conditions of illumination used. This is most relevant to the rapid epithelial spread of fluorescein from sites of punctate staining, compared to the apparent confinement of dyes to staining cells with dyes such as lissamine green and rose bengal. We assume that fluorescein, with its lower molecular weight, spreads initially by a paracellular route and then by transcellular diffusion. Solution-Induced Corneal Staining (SICS), related to the use of certain contact lens care solutions, may have a different basis, involving the non-pathological uptake of cationic preservatives, such as biguanides, into epithelial membranes and secondary binding of the fluorescein anion. It is transient and may not imply corneal toxicity. Understanding the mechanism of staining is relevant to the standardisation of grading, to monitoring disease and to the conduct of clinical trials.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2014.10.001},
	author = {Bron, A J and Arg{\"u}eso, P and Irkec, M and Bright, F V}
}
@article {1125276,
	title = {TFOS DEWS II pathophysiology report},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {438-510},
	abstract = {The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sj{\"o}gren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.05.011},
	author = {Bron, Anthony J and de Paiva, Cintia S and Chauhan, Sunil K and Bonini, Stefano and Gabison, Eric E and Jain, Sandeep and Knop, Erich and Markoulli, Maria and Ogawa, Yoko and Perez, Victor and Uchino, Yuichi and Yokoi, Norihiko and Zoukhri, Driss and Sullivan, David A}
}
@article {1402574,
	title = {High prevalence of strabismic visual field expansion in pediatric homonymous hemianopia},
	journal = {PLoS One},
	volume = {13},
	number = {12},
	year = {2018},
	month = {2018},
	pages = {e0209213},
	abstract = {If homonymous hemianopia develops in childhood it is frequently accompanied by strabismus. In some of these cases the strabismus increases the size of the binocular visual field. We determined how prevalent visual-field-expanding strabismus is in children who have homonymous hemianopia. Medical records were examined from 103 hemianopic patients with exotropia (XT) or esotropia (ET). For each participant, we determined whether their strabismus was in a direction that resulted in visual field expansion (i.e. left exotropia with left homonymous hemianopia). Ages at which hemianopia and strabismus were first noted were compared to determine which developed first. The prevalence of XT (24\%) and ET (9\%) with homonymous hemianopia were both much higher than in the general population (1.5\% and 5\%, respectively). More strabismic eyes pointed to the blind than seeing side (62 vs 41, 60\% vs. 40\%, p = 0.02). Exotropic eyes were five times more likely to point to the blind side than esotropic eyes (85\% vs 15\%). Strabismus, especially exotropia, is much more common in pediatric homonymous hemianopia than in the general population. The strabismus is significantly more often in a visual field-expanding direction. These results support an adaptive role for the strabismus. Patients with HH and exotropia or esotropia should be aware that their visual field could be reduced by strabismus surgery.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0209213},
	author = {Bronstad, P Matthew and Peli, Eli and Liu, Rui and Doherty, Amy and Fulton, Anne B}
}
@article {541331,
	title = {Driving with Central Visual Field Loss II: How Scotomas above or below the Preferred Retinal Locus (PRL) Affect Hazard Detection in a Driving Simulator.},
	journal = {PLoS One},
	volume = {10},
	number = {9},
	year = {2015},
	month = {2015},
	pages = {e0136517},
	abstract = {We determined whether binocular central scotomas above or below the preferred retinal locus affect detection of hazards (pedestrians) approaching from the side. Seven participants with central field loss (CFL), and seven age-and sex-matched controls with normal vision (NV), each completed two sessions of 5 test drives (each approximately 10 minutes long) in a driving simulator. Participants pressed the horn when detecting pedestrians that appeared at one of four eccentricities (-14{\textdegree}, -4{\textdegree}, left, 4{\textdegree}, or 14{\textdegree}, right, relative to car heading). Pedestrians walked or ran towards the travel lane on a collision course with the participant{\textquoteright}s vehicle, thus remaining in the same area of the visual field, assuming participant{\textquoteright}s steady forward gaze down the travel lane. Detection rates were nearly 100\% for all participants. CFL participant reaction times were longer (median 2.27s, 95\% CI 2.13 to 2.47) than NVs (median 1.17s, 95\%CI 1.10 to 2.13; difference p\&lt;0.01), and CFL participants would have been unable to stop for 21\% of pedestrians, compared with 3\% for NV, p\&lt;0.001. Although the scotomas were not expected to obscure pedestrian hazards, gaze tracking revealed that scotomas did sometimes interfere with detection; late reactions usually occurred when pedestrians were entirely or partially obscured by the scotoma (time obscured correlated with reaction times, r = 0.57, p\&lt;0.001). We previously showed that scotomas lateral to the preferred retinal locus delay reaction times to a greater extent; however, taken together, the results of our studies suggest that any binocular CFL might negatively impact timely hazard detection while driving and should be a consideration when evaluating vision for driving.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0136517},
	author = {Bronstad, P Matthew and Albu, Amanda and Bowers, Alex R and Goldstein, Robert and Peli, Eli}
}
@article {1490459,
	title = {A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families},
	journal = {Hum Mol Genet},
	volume = {29},
	number = {6},
	year = {2020},
	month = {2020 Apr 15},
	pages = {967-979},
	abstract = {Inherited retinal degenerations (IRDs) are at the focus of current genetic therapeutic advancements. For a genetic treatment such as gene therapy to be successful, an accurate genetic diagnostic is required. Genetic diagnostics relies on the assessment of the probability that a given DNA variant is pathogenic. Non-coding variants present a unique challenge for such assessments as compared to coding variants. For one, non-coding variants are present at much higher number in the genome than coding variants. In addition, our understanding of the rules that govern the non-coding regions of the genome is less complete than our understanding of the coding regions. Methods that allow for both the identification of candidate non-coding pathogenic variants and their functional validation may help overcome these caveats allowing for a greater number of patients to benefit from advancements in genetic therapeutics. We present here an unbiased approach combining whole genome sequencing (WGS) with patient-induced pluripotent stem cell (iPSC)-derived retinal organoids (ROs) transcriptome analysis. With this approach, we identified and functionally validated a novel pathogenic non-coding variant in a small family with a previously unresolved genetic diagnosis.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddaa016},
	author = {Bronstein, Revital and Capowski, Elizabeth E and Mehrotra, Sudeep and Jansen, Alex D and Navarro-Gomez, Daniel and Maher, Mathew and Place, Emily and Sangermano, Riccardo and Bujakowska, Kinga M and Gamm, David M and Pierce, Eric A}
}
@article {1589748,
	title = {Targeting the YAP/TAZ Pathway in Uveal and Conjunctival Melanoma With Verteporfin},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {62},
	number = {4},
	year = {2021},
	month = {2021 Apr 01},
	pages = {3},
	abstract = {Purpose: The purpose of this study was to determine whether YAP/TAZ activation in uveal melanoma (UM) and the susceptibility of melanoma cell lines to YAP/TAZ inhibition by verteporfin (VP) is related to the tumor{\textquoteright}s genetic background. Methods: Characteristics of 144 patients with enucleated UM were analyzed together with mRNA expression levels of YAP/TAZ-related genes (80 patients from the The Cancer Genome Atlas [TCGA] project and 64 patients from Leiden, The Netherlands). VP was administered to cell lines 92.1, OMM1, Mel270, XMP46, and MM28 (UM), CRMM1 and CRMM2 (conjunctival melanoma), and OCM3 (cutaneous melanoma). Viability, growth speed, and expression of YAP1-related proteins were assessed. Results: In TCGA data, high expression of YAP1 and WWTR1 correlated with the presence of monosomy 3 (P = 0.009 and P \&lt; 0.001, respectively) and BAP1-loss (P = 0.003 and P = 0.001, respectively) in the primary UM; metastasis development correlated with higher expression of YAP1 (P = 0.05) and WWTR1 (P = 0.003). In Leiden data, downstream transcription factor TEAD4 was increased in cases with M3/BAP1-loss (P = 0.002 and P = 0.006) and related to metastasis (P = 0.004). UM cell lines 92.1, OMM1, and Mel270 (GNAQ/11-mutation, BAP1-positive) and the fast-growing cell line OCM3 (BRAF-mutation) showed decreased proliferation after exposure to VP. Two slow-growing UM cell lines XMP46 and MM28 (GNAQ/11-mutation, BAP1-negative) were not sensitive to VP, and neither were the two conjunctival melanoma cell lines (BRAF/NRAS-mutation). Conclusions: High risk UM showed an increased expression of YAP/TAZ-related genes. Although most UM cell lines responded in vitro to VP, BAP1-negative and conjunctival melanoma cell lines did not. Not only the mutational background, but also cell growth rate is an important predictor of response to YAP/TAZ inhibition by VP.},
	issn = {1552-5783},
	doi = {10.1167/iovs.62.4.3},
	author = {Brouwer, Niels J and Konstantinou, Eleni K and Gragoudas, Evangelos S and Marinkovic, Marina and Luyten, Gregorius P M and Kim, Ivana K and Jager, Martine J and Vavvas, Demetrios G}
}
@article {1709746,
	title = {Expression of NMNAT1 in the photoreceptors is sufficient to prevent NMNAT1-associated retinal degeneration},
	journal = {Mol Ther Methods Clin Dev},
	volume = {29},
	year = {2023},
	month = {2023 Jun 08},
	pages = {319-328},
	abstract = {Nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is a ubiquitously expressed enzyme involved in nuclear NAD+ production throughout the body. However, mutations in the NMNAT1 gene lead to retina-specific disease with few reports of systemic effects. We have previously demonstrated that AAV-mediated gene therapy using self-complementary AAV (scAAV) to ubiquitously express NMNAT1 throughout the retina prevents retinal degeneration in a mouse model of NMNAT1-associated disease. We aimed to develop a better understanding of the cell types in the retina that contribute to disease pathogenesis in NMNAT1-associated disease, and to identify the cell types that require NMNAT1 expression for therapeutic benefit. To achieve this goal, we treated Nmnat1V9M/V9M mice with scAAV using cell type-specific promoters to restrict NMNAT1 expression to distinct retinal cell types. We hypothesized that photoreceptors are uniquely vulnerable to NAD+ depletion due to mutations in NMNAT1. Consistent with this hypothesis, we identified that treatments that drove NMNAT1 expression in the photoreceptors led to preservation of retinal morphology. These findings suggest that gene therapies for NMNAT1-associated disease should aim to express NMNAT1 in the photoreceptor cells.},
	issn = {2329-0501},
	doi = {10.1016/j.omtm.2023.04.003},
	author = {Brown, Emily E and Scandura, Michael J and Pierce, Eric A}
}
@article {1307454,
	title = {The Influence of Corneal Biomechanical Properties on Intraocular Pressure Measurements Using a Rebound Self-tonometer},
	journal = {J Glaucoma},
	volume = {27},
	number = {6},
	year = {2018},
	month = {2018 Jun},
	pages = {511-518},
	abstract = {PURPOSE: The purpose of this study was to examine the effect of corneal biomechanical properties on intraocular pressure (IOP) measurements obtained using a rebound self-tonometer (Icare HOME) compared with Goldmann applanation tonometry (GAT).

METHODS: An observational study of 100 patients with glaucoma or ocular hypertension. All had a comprehensive ophthalmic examination and standard automated perimetry. IOP was assessed by GAT, Icare HOME and Ocular Response Analyzer, which was also used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Central corneal thickness (CCT) was recorded.

RESULTS: Mean ({\textpm}SD) IOP measurements were 14.3{\textpm}3.9 and 11.7{\textpm}4.7 mm Hg using GAT and Icare HOME, respectively. Average CCT, CRF, and CH were 534.5{\textpm}37.3 μm, 9.0{\textpm}1.7 mm Hg, and 9.4{\textpm}1.5 mm Hg, respectively. The mean difference between Icare HOME and GAT was -2.66{\textpm}3.13 mm Hg, with 95\% limits of agreement of -8.80 to 3.48 mm Hg, however, there was evidence of proportional bias. There was negative correlation between IOP and CH [5.17 mm Hg higher Icare HOME IOP (P=0.041, R=0.029) and 7.23 mm Hg higher GAT IOP (P=0.008, R=0.080) for each 10 mm Hg lower CH], whereas thinner CCT was significantly associated with lower IOP (P,
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000948},
	author = {Brown, Lyndsay and Foulsham, William and Pronin, Savva and Tatham, Andrew J}
}
@article {1623362,
	title = {Reduced nuclear NAD+ drives DNA damage and subsequent immune activation in the retina},
	journal = {Hum Mol Genet},
	volume = {31},
	number = {9},
	year = {2022},
	month = {2022 05 04},
	pages = {1370-1388},
	abstract = {Mutations in NMNAT1, a key enzyme involved in the synthesis of NAD+ in the nucleus, lead to an early onset severe inherited retinal degeneration (IRD). We aimed to understand the role of nuclear NAD+ in the retina and to identify the molecular mechanisms underlying NMNAT1-associated disease, using a mouse model that harbors the p.V9M mutation in Nmnat1 (Nmnat1V9M/V9M). We identified temporal transcriptional reprogramming in the retinas of Nmnat1V9M/V9M mice prior to retinal degeneration, which begins at 4\&nbsp;weeks of age, with no significant alterations in gene expression at 2\&nbsp;weeks of age and over 2600 differentially expressed genes by 3\&nbsp;weeks of age. Expression of the primary consumer of NAD+ in the nucleus, PARP1, an enzyme involved in DNA damage repair and transcriptional regulation, as well as 7 other PARP family enzymes, was elevated in the retinas of Nmnat1V9M/V9M. This was associated with elevated levels of DNA damage, PARP-mediated NAD+ consumption and migration of Iba1+/CD45+ microglia/macrophages to the subretinal space in the retinas of Nmnat1V9M/V9M mice. These findings suggest that photoreceptor cells are especially sensitive to perturbation of genome homeostasis, and that PARP-mediated cell death may play a role in other genetic forms of IRDs, and potentially other forms of neurodegeneration.},
	keywords = {DNA Damage, Humans, NAD, Nicotinamide-Nucleotide Adenylyltransferase, Poly(ADP-ribose) Polymerase Inhibitors, Retina, Retinal Degeneration},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddab324},
	author = {Brown, Emily E and Scandura, Michael J and Mehrotra, Sudeep and Wang, Yekai and Du, Jianhai and Pierce, Eric A}
}
@article {1732696,
	title = {Deep Learning for Localized Detection of Optic Disc Hemorrhages},
	journal = {Am J Ophthalmol},
	volume = {255},
	year = {2023},
	month = {2023 Nov},
	pages = {161-169},
	abstract = {PURPOSE: To develop an automated deep learning system for detecting the presence and location of disc hemorrhages in optic disc photographs. DESIGN: Development and testing of a deep learning algorithm. METHODS: Optic disc photos (597 images with at least 1 disc hemorrhage and 1075 images without any disc hemorrhage from 1562 eyes) from 5 institutions were classified by expert graders based on the presence or absence of disc hemorrhage. The images were split into training (n\&nbsp;=\&nbsp;1340), validation (n\&nbsp;=\&nbsp;167), and test (n\&nbsp;=\&nbsp;165) datasets. Two state-of-the-art deep learning algorithms based on either object-level detection or image-level classification were trained on the dataset. These models were compared to one another and against 2 independent glaucoma specialists. We evaluated model performance by the area under the receiver operating characteristic curve (AUC). AUCs were compared with the Hanley-McNeil method. RESULTS: The object detection model achieved an AUC of 0.936 (95\% CI\&nbsp;=\&nbsp;0.857-0.964) across all held-out images (n\&nbsp;=\&nbsp;165 photographs), which was significantly superior to the image classification model (AUC\&nbsp;=\&nbsp;0.845, 95\% CI\&nbsp;=\&nbsp;0.740-0.912; P\&nbsp;=\&nbsp;.006). At an operating point selected for high specificity, the model achieved a specificity of 94.3\% and a sensitivity of 70.0\%, which was statistically indistinguishable from an expert clinician (P\&nbsp;=\&nbsp;.7). At an operating point selected for high sensitivity, the model achieves a sensitivity of 96.7\% and a specificity of 73.3\%. CONCLUSIONS: An autonomous object detection model is superior to an image classification model for detecting disc hemorrhages, and performed comparably to 2 clinicians.},
	keywords = {Algorithms, Deep Learning, Glaucoma, Humans, Optic Disk, Optic Nerve Diseases, Retinal Hemorrhage, ROC Curve},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.07.007},
	author = {Brown, Aaron and Cousins, Henry and Cousins, Clara and Esquenazi, Karina and Tobias Elze and Harris, Alon and Filipowicz, Artur and Barna, Laura and Yonwook, Kim and Vinod, Kateki and Chadha, Nisha and Altman, Russ B and Coote, Michael and Pasquale, Louis R}
}
@article {655081,
	title = {Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports.},
	journal = {Am J Med Genet A},
	volume = {170},
	number = {5},
	year = {2016},
	month = {2016 May},
	pages = {1165-73},
	abstract = {Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention-deficit hyperactivity disorder. Adolescent/adult- onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin-proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis. {\textcopyright} 2016 Wiley Periodicals, Inc.},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.37595},
	author = {Brownstein, Catherine A and Kleiman, Robin J and Engle, Elizabeth C and Towne, Meghan C and D{\textquoteright}Angelo, Eugene J and Yu, Timothy W and Beggs, Alan H and Picker, Jonathan and Fogler, Jason M and Carroll, Devon and Schmitt, Rachel C O and Wolff, Robert R and Shen, Yiping and Lip, Va and Bilguvar, Kaya and Kim, April and Tembulkar, Sahil and O{\textquoteright}Donnell, Kyle and Gonzalez-Heydrich, Joseph}
}
@article {1573133,
	title = {Genomic and Functional Characterization of Enterococcus faecalis Isolates Recovered From the International Space Station and Their Potential for Pathogenicity},
	journal = {Front Microbiol},
	volume = {11},
	year = {2020},
	month = {2020},
	pages = {515319},
	abstract = {is a multidrug resistant, opportunistic human pathogen and a leading cause of hospital acquired infections. Recently, isolates have been recovered from the air and surfaces onboard the International Space Station (ISS). Pangenomic and functional analyses were carried out to assess their potential impact on astronaut health. Genomes of each ISS isolate, and both clinical and commensal reference strains, were evaluated for their core and unique gene content, acquired antibiotic resistance genes, phage, plasmid content, and virulence traits. In order to determine their potential survival when outside of the human host, isolates were also challenged with three weeks of desiccation at 30\% relative humidity. Finally, pathogenicity of the ISS strains was evaluated in the model organism At the culmination of this study, there were no defining signatures that separated known pathogenic strains from the more commensal phenotypes using the currently available resources. As a result, the current reliance on database information alone must be shifted to experimentally evaluated genotypic and phenotypic characteristics of clinically relevant microorganisms.},
	issn = {1664-302X},
	doi = {10.3389/fmicb.2020.515319},
	author = {Bryan, Noelle C and Lebreton, Francois and Gilmore, Michael and Ruvkun, Gary and Zuber, Maria T and Christopher E. Carr}
}
@article {1478321,
	title = {AAV-Mediated Gene Augmentation Therapy Restores Critical Functions in Mutant PRPF31 iPSC-Derived RPE Cells},
	journal = {Mol Ther Methods Clin Dev},
	volume = {15},
	year = {2019},
	month = {2019 Dec 13},
	pages = {392-402},
	abstract = {Retinitis pigmentosa (RP) is the most common form of inherited vision loss and is characterized by degeneration of retinal photoreceptor cells and the retinal pigment epithelium (RPE). Mutations in pre-mRNA processing factor 31 () cause dominant RP via haploinsufficiency with incomplete penetrance. There is good evidence that the diverse severity of this disease is a result of differing levels of expression of the wild-type allele among patients. Thus, we hypothesize that -related RP will be amenable to treatment by adeno-associated virus (AAV)-mediated gene augmentation therapy. To test this hypothesis, we used induced pluripotent stem cells (iPSCs) with mutations in and differentiated them into RPE cells. The mutant iPSC-RPE cells recapitulate the cellular phenotype associated with the PRPF31 pathology, including defective cell structure, diminished phagocytic function, defects in ciliogenesis, and compromised barrier function. Treatment of the mutant iPSC-RPE cells with AAV- restored normal phagocytosis and cilia formation, and it partially restored structure and barrier function. These results suggest that AAV-based gene therapy targeting RPE cells holds therapeutic promise for patients with -related RP.},
	issn = {2329-0501},
	doi = {10.1016/j.omtm.2019.10.014},
	author = {Brydon, Elizabeth M and Bronstein, Revital and Buskin, Adriana and Lako, Majlinda and Pierce, Eric A and Fernandez-Godino, Rosario}
}
@article {1645489,
	title = {Clinical Correlation Between Vertical Gaze Palsy and Midbrain Volume in Progressive Supranuclear Palsy},
	journal = {J Neuroophthalmol},
	volume = {42},
	number = {2},
	year = {2022},
	month = {2022 06 01},
	pages = {246-250},
	abstract = {BACKGROUND: Supranuclear vertical gaze palsies and slowed vertical saccades are characteristic clinic features of progressive supranuclear palsy (PSP). The "hummingbird sign," reflective of midbrain atrophy, is a classic radiographic sign of PSP. Correlation between eye movement abnormalities and radiographic findings in PSP has been reported previously. However, due to the use of clinical criteria not commonly employed in neuro-ophthalmic practice and neuroimaging techniques that are not widely available, it remains unclear whether correlation between midbrain structure and characteristic ocular-motor disturbances can be helpful to neuro-ophthalmologists seeking to adjudicate difficult or unusual diagnostic cases. METHODS: Patients with a diagnosis of probable PSP according to Movement Disorders Society criteria were studied retrospectively. A neuroradiologist calculated brainstem volumes in enrolled participants and normal controls. Spearman correlations were used to correlate the extent of eye movement limitation as assessed by 2 neuro-ophthalmologists with brainstem volumes. RESULTS: Fourteen participants with PSP and 15 healthy controls with similar age and gender distribution were enrolled and evaluated retrospectively. All 14 participants with PSP had undergone MRIs. Midbrain atrophy significantly correlated with the PSP rating scale (P \&lt; 0.001). PSP patients had significantly reduced volumes in the midbrain (P -0.0026), tegmentum (0.0001), tectum (0.0001), and medulla (P = 0.0024) compared with normal controls. Notes documenting quantified ocular motor function were available in 7 of 14 participants with PSP. Midbrain atrophy significantly correlated with in the extent of upward gaze limitation (P = 0.03). CONCLUSIONS: The severity of upward gaze limitation correlates with the severity of midbrain atrophy in patients with PSP. Recognition of this correlation may help to adjudicate diagnostic dilemmas and guide further evaluation.},
	keywords = {Atrophy, Humans, Magnetic Resonance Imaging, Mesencephalon, Retrospective Studies, Strabismus, Supranuclear Palsy, Progressive, Tegmentum Mesencephali},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001393},
	author = {Buch, Karen A and Bouffard, Marc A and Kardon, Randy H and Wills, Anne-Marie A and Privitera, Claudio M and Sharma, Mansi and Wray, Shirley H}
}
@article {1789051,
	title = {Sympathetic Ophthalmia in Patients with Enucleation or Evisceration: Pathology Laboratory and IRIS Registry Experience},
	journal = {Ocul Oncol Pathol},
	volume = {9},
	number = {5-6},
	year = {2023},
	month = {2023 Dec},
	pages = {138-151},
	abstract = {INTRODUCTION: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. METHODS: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS{\textregistered} Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. RESULTS: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2\% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3\%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50\% (10/20), nonsurgical trauma in 45\% (9/20), and missing/undetermined in 5\% (1/20). SO was suspected preoperatively in 7/20 (35\%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5\%) and 872/9,092 (10\%) patients, respectively. In the IRIS Registry, 0.7\% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01\% (7,371/62,318,249); of these 7,371 cases, 199 (3\%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4\%) and 63 (0.2\%) cases, respectively. CONCLUSION: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.},
	issn = {2296-4681},
	doi = {10.1159/000533310},
	author = {Bui, Khanh and Tomaiuolo, Maurizio and Carter, Kaylene and Iacob, Codrin and Neerukonda, Vamsee and Stagner, Anna and Sajjadi, Zaynab and Escobar, Katherine V and Ordo{\~n}ez Armijos, Paula and Eagle, Ralph C and Mehta, Sonia and Dunn, James P and Hyman, Leslie and Milman, Tatyana and IRIS Registry Analytic Center Consortium}
}
@article {410371,
	title = {Targeted exon sequencing in Usher syndrome type I.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {12},
	year = {2014},
	month = {2014 Dec},
	pages = {8488-96},
	abstract = {PURPOSE: Patients with Usher syndrome type I (USH1) have retinitis pigmentosa, profound congenital hearing loss, and vestibular ataxia. This syndrome is currently thought to be associated with at least six genes, which are encoded by over 180 exons. Here, we present the use of state-of-the-art techniques in the molecular diagnosis of a cohort of 47 USH1 probands. METHODS: The cohort was studied with selective exon capture and next-generation sequencing of currently known inherited retinal degeneration genes, comparative genomic hybridization, and Sanger sequencing of new USH1 exons identified by human retinal transcriptome analysis. RESULTS: With this approach, we were able to genetically solve 14 of the 47 probands by confirming the biallelic inheritance of mutations. We detected two likely pathogenic variants in an additional 19 patients, for whom family members were not available for cosegregation analysis to confirm biallelic inheritance. Ten patients, in addition to primary disease-causing mutations, carried rare likely pathogenic USH1 alleles or variants in other genes associated with deaf-blindness, which may influence disease phenotype. Twenty-one of the identified mutations were novel among the 33 definite or likely solved patients. Here, we also present a clinical description of the studied cohort at their initial visits. CONCLUSIONS: We found a remarkable genetic heterogeneity in the studied USH1 cohort with multiplicity of mutations, of which many were novel. No obvious influence of genotype on phenotype was found, possibly due to small sample sizes of the genotypes under study.},
	keywords = {Adult, Cohort Studies, DNA Mutational Analysis, Exons, Gene Expression Profiling, Genetic Variation, Humans, Mutation, Myosins, Pedigree, Sequence Analysis, DNA, Usher Syndromes},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15169},
	author = {Bujakowska, Kinga M and Consugar, Mark and Place, Emily and Harper, Shyana and Lena, Jaclyn and Taub, Daniel G and White, Joseph and Navarro-Gomez, Daniel and Weigel DiFranco, Carol and Farkas, Michael H and Gai, Xiaowu and Berson, Eliot L and Pierce, Eric A}
}
@article {1538338,
	title = {Moving Towards PDE6A Gene Supplementation Therapy},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Oct 15},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.4216},
	author = {Bujakowska, Kinga M and Comander, Jason}
}
@article {931031,
	title = {Copy-number variation is an important contributor to the genetic causality of inherited retinal degenerations},
	journal = {Genet Med},
	volume = {19},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {643-651},
	abstract = {PURPOSE: Despite substantial progress in sequencing, current strategies can genetically solve only approximately 55-60\% of inherited retinal degeneration (IRD) cases. This can be partially attributed to elusive mutations in the known IRD genes, which are not easily identified by the targeted next-generation sequencing (NGS) or Sanger sequencing approaches. We hypothesized that copy-number variations (CNVs) are a major contributor to the elusive genetic causality of IRDs. METHODS: Twenty-eight cases previously unsolved with a targeted NGS were investigated with whole-genome single-nucleotide polymorphism (SNP) and comparative genomic hybridization (CGH) arrays. RESULTS: Deletions in the IRD genes were detected in 5 of 28 families, including a de novo deletion. We suggest that the de novo deletion occurred through nonallelic homologous recombination (NAHR) and we constructed a genomic map of NAHR-prone regions with overlapping IRD genes. In this article, we also report an unusual case of recessive retinitis pigmentosa due to compound heterozygous mutations in SNRNP200, a gene that is typically associated with the dominant form of this disease. CONCLUSIONS: CNV mapping substantially increased the genetic diagnostic rate of IRDs, detecting genetic causality in 18\% of previously unsolved cases. Extending the search to other structural variations will probably demonstrate an even higher contribution to genetic causality of IRDs.Genet Med advance online publication 13 October 2016.},
	issn = {1530-0366},
	doi = {10.1038/gim.2016.158},
	author = {Bujakowska, Kinga M and Fernandez-Godino, Rosario and Place, Emily and Consugar, Mark and Navarro-Gomez, Daniel and White, Joseph and Bedoukian, Emma C and Zhu, Xiaosong and Xie, Hongbo M and Gai, Xiaowu and Leroy, Bart P and Pierce, Eric A}
}
@article {1043206,
	title = {Photoreceptor Cilia and Retinal Ciliopathies},
	journal = {Cold Spring Harb Perspect Biol},
	volume = {9},
	number = {10},
	year = {2017},
	month = {2017 Oct 03},
	abstract = {Photoreceptors are sensory neurons designed to convert light stimuli into neurological responses. This process, called phototransduction, takes place in the outer segments (OS) of rod and cone photoreceptors. OS are specialized sensory cilia, with analogous structures to those present in other nonmotile cilia. Deficient morphogenesis and/or dysfunction of photoreceptor sensory cilia (PSC) caused by mutations in a variety of photoreceptor-specific and common cilia genes can lead to inherited retinal degenerations (IRDs). IRDs can manifest as isolated retinal diseases or syndromic diseases. In this review, we describe the structure and composition of PSC and different forms of ciliopathies with retinal involvement. We review the genetics of the IRDs, which are monogenic disorders but genetically diverse with regard to causality.},
	issn = {1943-0264},
	doi = {10.1101/cshperspect.a028274},
	author = {Bujakowska, Kinga M and Liu, Qin and Pierce, Eric A}
}
@article {314106,
	title = {Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome},
	journal = {Hum Mol Genet},
	volume = {24},
	number = {1},
	year = {2015},
	month = {2015 Jan 01},
	pages = {230-42},
	abstract = {Primary cilia are sensory organelles present on most mammalian cells. The assembly and maintenance of primary cilia are facilitated by intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium. Mutations in genes coding for IFT components have been associated with a group of diseases called ciliopathies. These genetic disorders can affect a variety of organs including the retina. Using whole exome sequencing in three families, we identified mutations in Intraflagellar Transport 172 Homolog [IFT172 (Chlamydomonas)] that underlie an isolated retinal degeneration and Bardet-Biedl syndrome. Extensive functional analyses of the identified mutations in cell culture, rat retina and in zebrafish demonstrated their hypomorphic or null nature. It has recently been reported that mutations in IFT172 cause a severe ciliopathy syndrome involving skeletal, renal, hepatic and retinal abnormalities (Jeune and Mainzer-Saldino syndromes). Here, we report for the first time that mutations in this gene can also lead to an isolated form of retinal degeneration. The functional data for the mutations can partially explain milder phenotypes; however, the involvement of modifying alleles in the IFT172-associated phenotypes cannot be excluded. These findings expand the spectrum of disease associated with mutations in IFT172 and suggest that mutations in genes originally reported to be associated with syndromic ciliopathies should also be considered in subjects with non-syndromic retinal dystrophy.},
	keywords = {Adolescent, Adult, Animals, Bardet-Biedl Syndrome, Carrier Proteins, Cells, Cultured, Exome, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Mutation, Pedigree, Rats, Retina, Retinitis Pigmentosa, Sequence Analysis, DNA, Young Adult, Zebrafish},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddu441},
	author = {Bujakowska, Kinga M and Zhang, Qi and Siemiatkowska, Anna M and Liu, Qin and Place, Emily and Falk, Marni J and Consugar, Mark and Lancelot, Marie-Elise and Antonio, Aline and Lonjou, Christine and Carpentier, Wassila and Mohand-Sa{\"\i}d, Saddek and den Hollander, Anneke I and Cremers, Frans P M and Leroy, Bart P and Gai, Xiaowu and Sahel, Jos{\'e}-Alain and van den Born, L Ingeborgh and Collin, Rob W J and Zeitz, Christina and Audo, Isabelle and Pierce, Eric A}
}
@article {1452978,
	title = {Placental CpG Methylation of Inflammation, Angiogenic, and Neurotrophic Genes and Retinopathy of Prematurity},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {8},
	year = {2019},
	month = {2019 Jul 01},
	pages = {2888-2894},
	abstract = {Purpose: Extremely preterm infants are at increased risk for retinopathy of prematurity (ROP). We previously identified several inflammatory proteins that were expressed early in life and are associated with an increased risk of ROP and several angiogenic and neurotrophic growth factors in the neonatal systemic circulation that are associated with a lower risk of ROP. In this paper, we report the results of a set of analyses designed to test the hypothesis that placental CpG methylation levels of 12 inflammation-, angiogenic-, and neurotrophic-associated genes predict the occurrence of prethreshold ROP in extremely preterm newborns. Methods: We used placental CpG methylation data from 395 newborns from the Extremely Low Gestational Age Newborns study. Results: Multivariable regression models revealed that placental DNA methylation of 16 CpG sites representing 8 genes were associated with prethreshold ROP. Specifically, CpG methylation in the serum amyloid A SAA1 and SAA2, brain-derived neurotrophic factor (BDNF), myeloperoxidase (MPO), C-reactive protein (CRP), angiopoietin 1 (ANGPT1), and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) genes was associated with a lower risk of prethreshold ROP. Conversely, CpG methylation at three probes within tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and in two alternative probes within the BDNF and ANGPT1 genes was associated with an increased risk of ROP. Conclusions: CpG methylation may be a useful marker for improving ROP prediction, opening the opportunity for early intervention to lessen disease severity.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-26466},
	author = {Bulka, Catherine M and Dammann, Olaf and Santos, Hudson P and VanderVeen, Deborah K and Smeester, Lisa and Fichorova, Raina and O{\textquoteright}Shea, T Michael and Fry, Rebecca C}
}
@article {382396,
	title = {Experimental glaucoma induced by ocular injection of magnetic microspheres.},
	journal = {J Vis Exp},
	number = {96},
	year = {2015},
	month = {2015},
	abstract = {Progress in understanding the pathophysiology, and providing novel treatments for glaucoma is dependent on good animal models of the disease. We present here a protocol for elevating intraocular pressure (IOP) in the rat, by injecting magnetic microspheres into the anterior chamber of the eye. The use of magnetic particles allows the user to manipulate the beads into the iridocorneal angle, thus providing a very effective blockade of fluid outflow from the trabecular meshwork. This leads to long-lasting IOP rises, and eventually neuronal death in the ganglion cell layer (GCL) as well as optic nerve pathology, as seen in patients with the disease. This method is simple to perform, as it does not require machinery, specialist surgical skills, or many hours of practice to perfect. Furthermore, the pressure elevations are very robust, and reinjection of the magnetic microspheres is not usually required unlike in some other models using plastic beads. Additionally, we believe this method is suitable for adaptation for the mouse eye.},
	issn = {1940-087X},
	doi = {10.3791/52400},
	author = {Bunker, Shannon and Holeniewska, Joanna and Vijay, Sauparnika and Dahlmann-Noor, Annegret and Khaw, Peng and Ng, Yin-Shan and Shima, David and Foxton, Richard}
}
@article {1364586,
	title = {Depression-biased reverse plasticity rule is required for stable learning at top-down connections},
	journal = {PLoS Comput Biol},
	volume = {8},
	number = {3},
	year = {2012},
	month = {2012},
	pages = {e1002393},
	abstract = {Top-down synapses are ubiquitous throughout neocortex and play a central role in cognition, yet little is known about their development and specificity. During sensory experience, lower neocortical areas are activated before higher ones, causing top-down synapses to experience a preponderance of post-synaptic activity preceding pre-synaptic activity. This timing pattern is the opposite of that experienced by bottom-up synapses, which suggests that different versions of spike-timing dependent synaptic plasticity (STDP) rules may be required at top-down synapses. We consider a two-layer neural network model and investigate which STDP rules can lead to a distribution of top-down synaptic weights that is stable, diverse and avoids strong loops. We introduce a temporally reversed rule (rSTDP) where top-down synapses are potentiated if post-synaptic activity precedes pre-synaptic activity. Combining analytical work and integrate-and-fire simulations, we show that only depression-biased rSTDP (and not classical STDP) produces stable and diverse top-down weights. The conclusions did not change upon addition of homeostatic mechanisms, multiplicative STDP rules or weak external input to the top neurons. Our prediction for rSTDP at top-down synapses, which are distally located, is supported by recent neurophysiological evidence showing the existence of temporally reversed STDP in synapses that are distal to the post-synaptic cell body.},
	keywords = {Action Potentials, Computer Simulation, Humans, Long-Term Synaptic Depression, Models, Neurological, Neocortex, Nerve Net, Neural Inhibition, Neuronal Plasticity, Neurons, Synaptic Transmission},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1002393},
	author = {Burbank, Kendra S and Kreiman, Gabriel}
}
@article {1430521,
	title = {Neurobiology of Photophobia},
	journal = {J Neuroophthalmol},
	volume = {39},
	number = {1},
	year = {2019},
	month = {2019 Mar},
	pages = {94-102},
	abstract = {BACKGROUND: Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is processed have paved the way to a better understanding of the neurobiology of photophobia and the complexity of the symptoms triggered by light. PURPOSE: The purpose of this review is to summarize recent anatomical and physiological studies on the neurobiology of photophobia with emphasis on migraine. RECENT FINDINGS: Observations made in blind and seeing migraine patients, and in a variety of animal models, have led to the discovery of a novel retino-thalamo-cortical pathway that carries photic signal from melanopsinergic and nonmelanopsinergic retinal ganglion cells (RGCs) to thalamic neurons. Activity of these neurons is driven by migraine and their axonal projections convey signals about headache and light to multiple cortical areas involved in the generation of common migraine symptoms. Novel projections of RGCs into previously unidentified hypothalamic neurons that regulate parasympathetic and sympathetic functions have also been discovered. Finally, recent work has led to a novel understanding of color preference in migraine-type photophobia and of the roles played by the retina, thalamus, and cortex. SUMMARY: The findings provide a neural substrate for understanding the complexity of aversion to light in patients with migraine and neuro-ophthalmologic other disorders.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000766},
	author = {Burstein, Rami and Noseda, Rodrigo and Fulton, Anne B}
}
@article {1580501,
	title = {The Lancet Global Health Commission on Global Eye Health: vision beyond 2020},
	journal = {Lancet Glob Health},
	volume = {9},
	number = {4},
	year = {2021},
	month = {2021 04},
	pages = {e489-e551},
	keywords = {Advisory Committees, Blindness, Cost of Illness, Eye Diseases, Global Burden of Disease, Global Health, Health Services Accessibility, Humans, Quality of Health Care, Quality of Life, Sustainable Development},
	issn = {2214-109X},
	doi = {10.1016/S2214-109X(20)30488-5},
	author = {Burton, Matthew J and Ramke, Jacqueline and Marques, Ana Patricia and Bourne, Rupert R A and Congdon, Nathan and Jones, Iain and Ah Tong, Brandon A M and Arunga, Simon and Bachani, Damodar and Bascaran, Covadonga and Bastawrous, Andrew and Blanchet, Karl and Braithwaite, Tasanee and Buchan, John C and Cairns, John and Cama, Anasaini and Chagunda, Margarida and Chuluunkhuu, Chimgee and Cooper, Andrew and Crofts-Lawrence, Jessica and Dean, William H and Denniston, Alastair K and Ehrlich, Joshua R and Emerson, Paul M and Evans, Jennifer R and Frick, Kevin D and Friedman, David S and Furtado, Jo{\~a}o M and Gichangi, Michael M and Gichuhi, Stephen and Gilbert, Suzanne S and Gurung, Reeta and Habtamu, Esmael and Holland, Peter and Jonas, Jost B and Keane, Pearse A and Keay, Lisa and Khanna, Rohit C and Khaw, Peng Tee and Kuper, Hannah and Kyari, Fatima and Lansingh, Van C and Mactaggart, Islay and Mafwiri, Milka M and Mathenge, Wanjiku and McCormick, Ian and Morjaria, Priya and Mowatt, Lizette and Muirhead, Debbie and Murthy, Gudlavalleti V S and Mwangi, Nyawira and Patel, Daksha B and Peto, Tunde and Qureshi, Babar M and Salom{\~a}o, Solange R and Sarah, Virginia and Shilio, Bernadetha R and Solomon, Anthony W and Swenor, Bonnielin K and Taylor, Hugh R and Wang, Ningli and Webson, Aubrey and West, Sheila K and Wong, Tien Yin and Wormald, Richard and Yasmin, Sumrana and Yusufu, Mayinuer and Silva, Juan Carlos and Resnikoff, Serge and Ravilla, Thulasiraj and Gilbert, Clare E and Foster, Allen and Faal, Hannah B}
}
@article {1466900,
	title = {Real-world outcomes of non-responding diabetic macular edema treated with continued anti-VEGF therapy versus early switch to dexamethasone implant: 2-year results},
	journal = {Acta Diabetol},
	volume = {56},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {1341-1350},
	abstract = {AIMS: To provide 2-year follow-up data on eyes with diabetic macular edema (DME) that were non-responsive after three initial anti-vascular endothelial growth factor (VEGF) injections, comparing functional and anatomical outcomes under continued anti-VEGF therapy versus dexamethasone (DEX) implant. METHODS: Multicenter, retrospective chart review comparing eyes with treatment-na{\"\i}ve DME and a suboptimal response to a loading phase of anti-VEGF therapy (3 injections given monthly) which were then treated with (a) further anti-VEGF (n = 72) or (b) initially switched to DEX implant (n = 38). Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) from the end of the loading phase to 24\&nbsp;months. RESULTS: In 79\% of the 12-month study population (87/110 eyes), 24-month data were available. One quarter of eyes in each group switched treatments during the second year. Eyes that were switched early to DEX implant maintained the functional and anatomical improvements at 24\&nbsp;months which were seen in the first year (from month 3: + 8.9 letters, - 214\&nbsp;{\textmu}m). Eyes that were switched from anti-VEGF therapy to steroids in the second year improved VA and reduced CST at 24\&nbsp;months (from month 12: + 6.8 letters, p = 0.023; - 226\&nbsp;{\textmu}m, p = 0.004). In eyes continued on anti-VEGF therapy, VA and CST were stable at 24\&nbsp;months (from month 3: + 2.8 letters, p = 0.254; - 24\&nbsp;{\textmu}m, p = 0.243). Eyes that were non-responsive to anti-VEGF therapy for 12\&nbsp;months had similar chances to experience a VA gain from further therapy as eyes that were non-responsive for 3\&nbsp;months only (23.8 vs. 31.0\%, p = 0.344). CONCLUSIONS: The beneficial effect of an early switch to DEX implant in DME non-responders seen at month 12 was maintained during the second year. A later switch from anti-VEGF to steroids still provided significant improvement. Eyes continued on anti-VEGF over a period of 24\&nbsp;months maintained vision. A quarter of eyes, which had not improved vision at 12\&nbsp;months, exhibited a delayed response to treatment.},
	issn = {1432-5233},
	doi = {10.1007/s00592-019-01416-4},
	author = {Busch, Catharina and Fraser-Bell, Samantha and Iglicki, Matias and Lupidi, Marco and Couturier, Aude and Chaikitmongkol, Voraporn and Giancipoli, Ermete and Rodr{\'\i}guez-Vald{\'e}s, Patricio J and Gabrielle, Pierre-Henry and La{\'\i}ns, In{\^e}s and Santos, Ana Rita and Cebeci, Zafer and Amphornphruet, Atchara and Degenhardt, Valentin and Unterlauft, Jan-Darius and Cagini, Carlo and Man{\'e}-Tauty, Val{\'e}rie and Ricci, Giuseppe D{\textquoteright}Amico and Hindi, Isaac and Agrawal, Kushal and Chhablani, Jay and Loewenstein, Anat and Zur, Dinah and Rehak, Matus and International Retina Group}
}
@article {1430522,
	title = {Real-world outcomes of observation and treatment in diabetic macular edema with very good visual acuity: the OBTAIN study},
	journal = {Acta Diabetol},
	volume = {56},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {777-784},
	abstract = {AIMS: To describe and compare the functional and anatomical outcomes of untreated and treated diabetic macular edema (DME) in eyes with very good baseline visual acuity (VA) in a real-world setting. METHODS: A 12-month, retrospective, multicenter, observational cohort study, including DME patients with baseline visual acuity (VA) <= 0.1 logMAR (>= 20/25 Snellen) and central subfield thickness (CST) \&gt; 250\&nbsp;{\textmu}m with intra- and/or subretinal fluid seen on optical coherence tomography. RESULTS: A total of 249 eyes were included, of which 155 were treated and 94 were non-treated during follow-up. Most eyes maintained vision (VA gain or VA loss \&lt; 5 letters) at 12\&nbsp;months (treated: 58.1\%; non-treated: 73.4\%). In non-treated eyes with stable VA within the first 6\&nbsp;months, VA was maintained throughout the follow-up in most cases (86.3\%). In non-treated eyes with VA loss >= 5 letters within 6\&nbsp;months (36.7\%), further observation led to worse visual outcome than treatment (- 4.2 vs. - 7.8 letters, p = 0.013). In eyes in which treatment was initiated at baseline (n = 102), treatment with 8-12 anti-VEGF injections led to better visual outcome compared to treatment with less injections (- 0.3 {\textpm} 3.6 letters vs. - 3.8 {\textpm} 6.2 letters, p = 0.003). CONCLUSION: In a real-world setting, the majority of DME patients with very good VA maintained vision at 12\&nbsp;months, regardless of whether the DME was treated or not. This study supports close observation of eyes with DME and very good VA with consideration of treatment when a one line drop in vision is observed.},
	issn = {1432-5233},
	doi = {10.1007/s00592-019-01310-z},
	author = {Busch, Catharina and Fraser-Bell, Samantha and Zur, Dinah and Rodr{\'\i}guez-Vald{\'e}s, Patricio J and Cebeci, Zafer and Lupidi, Marco and Fung, Adrian T and Gabrielle, Pierre-Henry and Giancipoli, Ermete and Chaikitmongkol, Voraporn and Okada, Mali and La{\'\i}ns, In{\^e}s and Santos, Ana Rita and Kunavisarut, Paradee and Sala-Puigdollers, Anna and Chhablani, Jay and Ozimek, Malgorzata and Hilely, Assaf and Unterlauft, Jan Darius and Loewenstein, Anat and Iglicki, Matias and Rehak, Matus and International Retina Group}
}
@article {1498262,
	title = {Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity},
	journal = {Acta Ophthalmol},
	volume = {98},
	number = {7},
	year = {2020},
	month = {2020 Nov},
	pages = {e801-e806},
	abstract = {PURPOSE: To investigate clinical baseline characteristics and optical coherence tomography biomarkers predicting visual loss during observation in eyes with diabetic macular oedema (DMO) and good baseline visual acuity (VA). METHODS: A sub-analysis of a 12-month, retrospective study, including patients with baseline VA <=0.1 logMAR (>=20/25 Snellen) and centre-involving DMO. The primary outcome measure was the correlation between baseline characteristics and VA loss >=10 letters during follow-up. RESULTS: A total of 249 eyes were included in the initial study, of which 147 eyes were observed and 80 eyes received anti-vascular endothelial growth factor (VEGF) treatment at baseline. Visual acuity (VA) loss >=10 letters occurred in 21.8\% (observed cohort) and in 24.3\% (treated cohort), respectively. Within observed eyes, presence of hyperreflective foci [HRF; odds ratio (OR): 3.18, p\&nbsp;=\&nbsp;0.046], and disorganization of inner retina layers (DRIL; OR: 2.71, p\&nbsp;=\&nbsp;0.026) were associated with a higher risk of VA loss >=10 letters. In observed eyes with a combined presence of HRF, DRIL and ellipsoid zone (EZ) disruption, the risk of VA loss was further increased (OR: 3.86, p\&nbsp;=\&nbsp;0.034). In eyes with combined presence of DRIL, HRF and EZ disruption, risk of VA loss was 46.7\% (7/15 eyes) in the observed cohort, and 26.3\% (5/19 eyes) in the treated cohort (p\&nbsp;=\&nbsp;0.26). CONCLUSION: Patients with DMO and good baseline VA, managed by observation, are of increased risk for VA loss if DRIL, HRF and EZ disruption are present at baseline. Earlier treatment with anti-VEGF in these patients may potentially decrease the risk of VA loss at 12\&nbsp;months.},
	issn = {1755-3768},
	doi = {10.1111/aos.14390},
	author = {Busch, Catharina and Okada, Mali and Zur, Dinah and Fraser-Bell, Samantha and Rodr{\'\i}guez-Vald{\'e}s, Patricio J and Cebeci, Zafer and Lupidi, Marco and Fung, Adrian T and Gabrielle, Pierre-Henry and Giancipoli, Ermete and Chaikitmongkol, Voraporn and La{\'\i}ns, In{\^e}s and Santos, Ana Rita and Kunavisarut, Paradee and Sala-Puigdollers, Anna and Chhablani, Jay and Ozimek, Malgorzata and Hilely, Assaf and Degenhardt, Valentin and Loewenstein, Anat and Iglicki, Matias and Rehak, Matus and International Retina Group}
}
@article {1430523,
	title = {Causative Pathogens of Endophthalmitis after Intravitreal Anti-VEGF Injection: An International Multicenter Study},
	journal = {Ophthalmologica},
	volume = {241},
	number = {4},
	year = {2019},
	month = {2019 Mar 19},
	pages = {211-219},
	abstract = {PURPOSE: The main objective of this study was to investigate the microbiological spectrum of endophthalmitis after anti-VEGF injections and to compare streptococcal with non-streptococcus-associated cases with regard to baseline characteristics and injection procedure. METHODS: Retrospective, international multicenter study of patients with culture-positive endophthalmitis after intravitreal anti-VEGF injection at 17 different retina referral centers. RESULTS: Eighty-three cases with 87 identified pathogens were included. Coagulase-negative staphylococci (59\%) and viridans streptococci (15\%) were the most frequent pathogens found. The use of postoperative antibiotics and performance of injections in an operating room setting significantly reduced the rate of streptococcus-induced endophthalmitis cases (p = 0.01 for both). CONCLUSION: We found a statistically significant lower rate of postinjectional local antibiotic therapy and operating room-based procedures among the streptococcus-induced cases compared to cases caused by other organisms.},
	issn = {1423-0267},
	doi = {10.1159/000496942},
	author = {Busch, Catharina and Iglicki, Matias and Okada, Mali and Gabrielle, Pierre-Henry and Cohen, Shai and Mariussi, Miriana and Amphornphruet, Atchara and Cebeci, Zafer and Chaikitmongkol, Voraporn and Couturier, Aude and Fraser-Bell, Samantha and Fung, Adrian T and Iannetta, Danilo and Radecka, Liga and La{\'\i}ns, In{\^e}s and Rodrigues, Tiago M and Lupidi, Marco and Ozimek, Ma{\l}gorzata and Sala-Puigdollers, Anna and Rehak, Matus and Loewenstein, Anat and Zur, Dinah and for~the~International~Retina~Group~(IRG)}
}
@article {1328876,
	title = {Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema},
	journal = {Acta Diabetol},
	volume = {55},
	number = {8},
	year = {2018},
	month = {2018 Aug},
	pages = {789-796},
	abstract = {AIMS: To compare functional and anatomical outcomes of continued anti-vascular endothelial growth factor (VEGF) therapy versus dexamethasone (DEX) implant in eyes with refractory diabetic macular edema (DME) after three initial anti-VEGF injections in a real-world setting. METHODS: To be included in this retrospective multicenter, case-control study, eyes were required: (1) to present with early refractory DME, as defined by visual acuity (VA) gain <= 5 letters or reduction in central subfield thickness (CST) <= 20\%, after a loading phase of anti-VEGF therapy (three monthly injections) and (2) to treat further with (a) anti-VEGF therapy or (b) DEX implant. Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) at 12\&nbsp;months. Due to imbalanced baseline characteristics, a matched anti-VEGF group was formed by only keeping eyes with similar baseline characteristics as those in the DEX group. RESULTS: A total of 110 eyes from 105 patients were included (anti-VEGF group: 72 eyes, DEX group: 38 eyes). Mean change in VA at 12\&nbsp;months was - 0.4 {\textpm} 10.8 letters (anti-VEGF group), and + 6.1 {\textpm} 10.6 letters (DEX group) (P = 0.004). Over the same period, mean change in CST was + 18.3 {\textpm} 145.9\&nbsp;{\textmu}m (anti-VEGF group) and - 92.8 {\textpm} 173.6\&nbsp;{\textmu}m (DEX group) (P \&lt; 0.001). Eyes in the DEX group were more likely to gain >= 10 letters (OR 3.71, 95\% CI 1.19-11.61, P = 0.024) at month 12. CONCLUSIONS: In a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12\&nbsp;months than those that continued treatment with anti-VEGF therapy.},
	issn = {1432-5233},
	doi = {10.1007/s00592-018-1151-x},
	author = {Busch, Catharina and Zur, Dinah and Fraser-Bell, Samantha and La{\'\i}ns, In{\^e}s and Santos, Ana Rita and Lupidi, Marco and Cagini, Carlo and Gabrielle, Pierre-Henry and Couturier, Aude and Man{\'e}-Tauty, Val{\'e}rie and Giancipoli, Ermete and Ricci, Giuseppe D{\textquoteright}Amico and Cebeci, Zafer and Rodr{\'\i}guez-Vald{\'e}s, Patricio J and Chaikitmongkol, Voraporn and Amphornphruet, Atchara and Hindi, Isaac and Agrawal, Kushal and Chhablani, Jay and Loewenstein, Anat and Iglicki, Matias and Rehak, Matus and International Retina Group}
}
@article {1347429,
	title = {Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa},
	journal = {Nat Commun},
	volume = {9},
	number = {1},
	year = {2018},
	month = {2018 Oct 12},
	pages = {4234},
	abstract = {Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause non-syndromic retinal disease. Here, we generate transcriptome profiles from RP11 (PRPF31-mutated) patient-derived retinal organoids and retinal pigment epithelium (RPE), as well as Prpf31 mouse tissues, which revealed that disrupted alternative splicing occurred for specific splicing programmes. Mis-splicing of genes encoding pre-mRNA splicing proteins was limited to patient-specific retinal cells and Prpf31 mouse retinae and RPE. Mis-splicing of genes implicated in ciliogenesis and cellular adhesion was associated with severe RPE defects that include disrupted apical - basal polarity, reduced trans-epithelial resistance and phagocytic capacity, and decreased cilia length and incidence. Disrupted cilia morphology also occurred in patient-derived photoreceptors, associated with progressive degeneration and cellular stress. In situ gene editing of a pathogenic mutation rescued protein expression and key cellular phenotypes in RPE and photoreceptors, providing proof of concept for future therapeutic strategies.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-06448-y},
	author = {Buskin, Adriana and Zhu, Lili and Chichagova, Valeria and Basu, Basudha and Mozaffari-Jovin, Sina and Dolan, David and Droop, Alastair and Collin, Joseph and Bronstein, Revital and Mehrotra, Sudeep and Farkas, Michael and Hilgen, Gerrit and White, Kathryn and Pan, Kuan-Ting and Treumann, Achim and Hallam, Dean and Bialas, Katarzyna and Chung, Git and Mellough, Carla and Ding, Yuchun and Krasnogor, Natalio and Przyborski, Stefan and Zwolinski, Simon and Al-Aama, Jumana and Alharthi, Sameer and Xu, Yaobo and Wheway, Gabrielle and Szymanska, Katarzyna and McKibbin, Martin and Inglehearn, Chris F and Elliott, David J and Lindsay, Susan and Ali, Robin R and Steel, David H and Armstrong, Lyle and Sernagor, Evelyne and Urlaub, Henning and Pierce, Eric and L{\"u}hrmann, Reinhard and Grellscheid, Sushma-Nagaraja and Johnson, Colin A and Lako, Majlinda}
}
@article {1677811,
	title = {Dual-Energy X-Ray Absorptiometry Scan Utilization and Skeletal Fragility Among Non-Infectious Uveitis Patients Exposed to Oral Glucocorticoids},
	journal = {Ocul Immunol Inflamm},
	year = {2023},
	month = {2023 Mar 09},
	pages = {1-9},
	abstract = {INTRODUCTION: Currently, little is known regarding bone health surveillance for glucocorticoid-exposed non-infectious uveitis (NIU) patients or their baseline risks of skeletal fragility outcomes. METHODS: Using claims data, we calculated rates of dual-energy x-ray absorptiometry (DXA) screening for glucocorticoid-exposed NIU and rheumatoid arthritis (RA) patients. Separately, we compared risks of skeletal fragility metrics amongst NIU patients, RA patients, and controls, independent of glucocorticoid use. RESULTS: The adjusted hazard ratio (aHR) of NIU patients to have a DXA scan was 0.64 (95\% CI, 0.63-0.65; p \&lt;\&nbsp;.001) compared to RA patients. The aHR for any skeletal fragility outcome amongst NIU patients was 0.97 (p \&lt;\&nbsp;.02) compared to normal controls, while RA patients had excess risk (aHR, 1.15; p \&lt;\&nbsp;.001). CONCLUSIONS: NIU patients are 36\% less likely to receive a DXA scan after high-dose glucocorticoid exposure compared with RA patients. No elevated risk of osteoporosis for NIU patients was found compared to normal controls.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2023.2182793},
	author = {Butler, Nicholas J and Cohen, Devin and Yu, Yinxi and Kempen, John H and Sobrin, Lucia and VanderBeek, Brian L}
}
@article {1078721,
	title = {Acute Retinal Necrosis: Presenting Characteristics and Clinical Outcomes in a Cohort of Polymerase Chain Reaction-Positive Patients},
	journal = {Am J Ophthalmol},
	volume = {179},
	year = {2017},
	month = {2017 Jul},
	pages = {179-189},
	abstract = {PURPOSE: To identify determinants of adverse outcomes in acute retinal necrosis (ARN), presenting characteristics and incidence rates of vision loss and ocular complications in a cohort of polymerase chain reaction (PCR)-positive eyes were analyzed. DESIGN: Retrospective observational cohort study. METHODS: Forty-one eyes of 36 patients with clinically diagnosed ARN, PCR-positive for herpes simplex virus or varicella zoster virus and evaluated between January 2002 and June 2013, were included. Main outcome measures included incidence rates of vision loss and retinal detachment (RD). RESULTS: Presenting visual acuity was generally poor (20/50 to \&gt;20/200 in 27\%; 20/200 or worse in 56\%). The incidence rate of <=20/200 was 0.66/eye-year (EY), (95\% confidence interval [CI], 0.32/EY to 1.22/EY); the rate of light perception or no light perception vision was 0.07/EY (95\% CI, 0.02/EY to 0.16/EY). During follow-up, 59\% of eyes developed at least 1 RD (rate\&nbsp;=\&nbsp;0.40/EY, 95\% CI, 0.19/EY to 0.58/EY). Eyes with retinitis involving >=25\% of the retina at presentation detached at nearly 12 times the rate, as compared to those with \&lt;25\% retinal involvement (0.70/EY vs 0.06/EY; P\&nbsp;= .001). Development of an RD was the greatest determinant of adverse visual outcomes, with 4\% of eyes, that had experienced at least 1 RD, achieving a best-corrected visual acuity of >=20/40 compared to 53\% of eyes that never detached (P\&nbsp;= .0003). CONCLUSIONS: Poor outcomes in ARN were common in this cohort. RD confers the greatest risk of incident vision loss, and once 25\% or more of the retina is involved\&nbsp;the risk of RD and visual loss increases significantly.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Child, DNA, Viral, Eye Infections, Viral, Female, Follow-Up Studies, Herpes Simplex, Herpes Zoster Ophthalmicus, Herpesvirus 3, Human, Humans, Male, Middle Aged, Polymerase Chain Reaction, Retinal Necrosis Syndrome, Acute, Retrospective Studies, Visual Acuity, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.05.006},
	author = {Butler, Nicholas J and Moradi, Ahmadreza and Salek, Sherveen S and Burkholder, Bryn M and Leung, Theresa G and Dunn, James P and Thorne, Jennifer E}
}
@article {1351140,
	title = {Regulation of intraocular pressure by soluble and membrane guanylate cyclases and their role in glaucoma},
	journal = {Front Mol Neurosci},
	volume = {7},
	year = {2014},
	month = {2014},
	pages = {38},
	abstract = {Glaucoma is a progressive optic neuropathy characterized by visual field defects that ultimately lead to irreversible blindness (Alward, 2000; Anderson et al., 2006). By the year 2020, an estimated 80 million people will have glaucoma, 11 million of which will be bilaterally blind. Primary open-angle glaucoma (POAG) is the most common type of glaucoma. Elevated intraocular pressure (IOP) is currently the only risk factor amenable to treatment. How IOP is regulated and can be modulated remains a topic of active investigation. Available therapies, mostly geared toward lowering IOP, offer incomplete protection, and POAG often goes undetected until irreparable damage has been done, highlighting the need for novel therapeutic approaches, drug targets, and biomarkers (Heijl et al., 2002; Quigley, 2011). In this review, the role of soluble (nitric oxide (NO)-activated) and membrane-bound, natriuretic peptide (NP)-activated guanylate cyclases that generate the secondary signaling molecule cyclic guanosine monophosphate (cGMP) in the regulation of IOP and in the pathophysiology of POAG will be discussed.},
	issn = {1662-5099},
	doi = {10.3389/fnmol.2014.00038},
	author = {Buys, Emmanuel S and Potter, Lincoln R and Pasquale, Louis R and Ksander, Bruce R}
}
@article {1363251,
	title = {Soluble Guanylate Cyclase a1-Deficient Mice: a novel murine model for Primary Open Angle Glaucoma},
	journal = {Ann Neurosci},
	volume = {20},
	number = {2},
	year = {2013},
	month = {2013 Apr},
	pages = {65-6},
	issn = {0972-7531},
	doi = {10.5214/ans.0972.7531.200207},
	author = {Buys, Emmanuel S and Ko, Yu-Chieh and Alt, Clemens and Hayton, Sarah R and Jones, Alexander and Tainsh, Laurel T and Ren, Ruiyi and Giani, Andrea and Clerte{\textquoteright}, Maeva and Abernathy, Emma and Tainsh, Robert E T and Oh, Dong-Jin and Malhotra, Rajeev and Arora, Pankaj and de Waard, Nadine and Yu, Binglan and Turcotte, Raphael and Nathan, Daniel and Scherrer-Crosbie, Marielle and Loomis, Stephanie J and Kang, Jae H and Lin, Charles P and Gong, Haiyan and Rhee, Douglas J and Brouckaert, Peter and Wiggs, Janey L and Gregory, Meredith S and Pasquale, Louis R and Bloch, Kenneth D and Ksander, Bruce R}
}
@article {1642384,
	title = {A trans-orbital pencil in the left carotid artery of a 40-year-old man: clinical and radiographic images.},
	journal = {Orbit},
	year = {2022},
	author = {Chiou C and Reshef ER and Liebman D and Dwytriw AA and Vranic JE and Regenhardt RW and Patel AB and Stapleton C and Wolkow N}
}
@article {1351141,
	title = {Alkali burn to the eye: protection using TNF-α inhibition},
	journal = {Cornea},
	volume = {33},
	number = {4},
	year = {2014},
	month = {2014 Apr},
	pages = {382-9},
	abstract = {PURPOSE: The aim of this study was to evaluate early retinal damage after induction of ocular surface alkali burns and the protective effects of tumor necrosis factor alpha (TNF-α) blockade. METHODS: Alkali injury was induced in mouse corneas by using 1 N NaOH. Retinal damage was assessed using a terminal deoxynucleotidyl transferase 2{\textquoteright}-deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay, 15 minutes to 14 days postburn. Immune cell infiltration was assessed by CD45 immunolocalization. Retinal cytokines were quantified using the enzyme-linked immunosorbent assay for interleukin (IL)1β, IL2, IL6, TNF-α, CCL5, and macrophage inflammatory protein-1α. Protection against retinal damage was attempted with a single dose of either anti-TNF-α antibody (infliximab, 6.25 mg/kg) or control immunoglobulin G (IgG), administered intraperitoneally 15 minutes after the burn was inflicted. Corneal injury was evaluated by using TUNEL and CD45 immunolocalization and by quantifying corneal neovascularization. RESULTS: There was significant damage to the retina within 24 hours of the corneal burn being inflicted. TUNEL+ labeling was present in 80\% of the retinal ganglion cells, including a few CD45+ cells. There was a 10-fold increase in the retinal inflammatory cytokines in the study groups compared with that in controls. A single intraperitoneal dose of anti-TNF-α antibody, administered 15 minutes after the burn, markedly reduced retinal TUNEL+, CD45+ labeling, and inflammatory cytokine expression, compared with that in the controls. Additionally, TNF-α blockade caused a marked reduction in corneal neovascularization, and in cornea TUNEL and CD45 labeling, 5 days after the burn. CONCLUSIONS: This study shows that alkali corneal burns can induce significant retinal damage within 24 hours. A single dose of anti-TNF-α antibody, administered 15 minutes after inflicting the burn, provides significant retinal and corneal protection. This could lead to the discovery of novel therapies for patients with alkali injuries.},
	keywords = {Animals, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, Burns, Chemical, Corneal Diseases, Cytokines, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Eye Burns, Hydrogen-Ion Concentration, In Situ Nick-End Labeling, Infliximab, Injections, Intraperitoneal, Leukocyte Common Antigens, Male, Mice, Mice, Inbred BALB C, Retinal Diseases, Retinal Ganglion Cells, Sodium Hydroxide, Tumor Necrosis Factor-alpha},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000071},
	author = {Cade, Fabiano and Paschalis, Eleftherios I and Regatieri, Caio V and Vavvas, Demetrios G and Dana, Reza and Dohlman, Claes H}
}
@article {1789081,
	title = {Advancing Toward a Common Data Model in Ophthalmology: Gap Analysis of General Eye Examination Concepts to Standard Observational Medical Outcomes Partnership (OMOP) Concepts},
	journal = {Ophthalmol Sci},
	volume = {3},
	number = {4},
	year = {2023},
	month = {2023 Dec},
	pages = {100391},
	abstract = {PURPOSE: Evaluate the degree of concept coverage of the general eye examination in one widely used electronic health record (EHR) system using the Observational Health Data Sciences and Informatics Observational Medical Outcomes Partnership (OMOP) common data model (CDM). DESIGN: Study of data elements. PARTICIPANTS: Not applicable. METHODS: Data elements (field names and predefined entry values) from the general eye examination in the Epic foundation system were mapped to OMOP concepts and analyzed. Each mapping was given a Health Level 7 equivalence designation-equal when the OMOP concept had the same meaning as the source EHR concept, wider when it was missing information, narrower when it was overly specific, and unmatched when there was no match. Initial mappings were reviewed by 2 graders. Intergrader agreement for equivalence designation was calculated using Cohen{\textquoteright}s kappa. Agreement on the mapped OMOP concept was calculated as a percentage of total mappable concepts. Discrepancies were discussed and a final consensus created. Quantitative analysis was performed on wider and unmatched concepts. MAIN OUTCOME MEASURES: Gaps in OMOP concept coverage of EHR elements and intergrader agreement of mapped OMOP concepts. RESULTS: A total of 698 data elements (210 fields, 488 values) from the EHR were analyzed. The intergrader kappa on the equivalence designation was 0.88 (standard error 0.03, P\&nbsp;\&lt;\&nbsp;0.001). There was a 96\% agreement on the mapped OMOP concept. In the final consensus mapping, 25\% (1\% fields, 31\% values) of the EHR to OMOP concept mappings were considered equal, 50\% (27\% fields, 60\% values) wider, 4\% (8\% fields, 2\% values) narrower, and 21\% (52\% fields, 8\% values) unmatched. Of the wider mapped elements, 46\% were missing the laterality specification, 24\% had other missing attributes, and 30\% had both issues. Wider and unmatched EHR elements could be found in all areas of the general eye examination. CONCLUSIONS: Most data elements in the general eye examination could not be represented precisely using the OMOP CDM. Our work suggests multiple ways to improve the incorporation of important ophthalmology concepts in OMOP, including adding laterality to existing concepts. There exists a strong need to improve the coverage of ophthalmic concepts in source vocabularies so that the OMOP CDM can better accommodate vision research. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100391},
	author = {Cai, Cindy X and Halfpenny, William and Boland, Michael V and Lehmann, Harold P and Hribar, Michelle and Goetz, Kerry E and Baxter, Sally L}
}
@article {836771,
	title = {Clinical Correlates of Computationally Derived Visual Field Defect Archetypes in Patients from a Glaucoma Clinic},
	journal = {Curr Eye Res},
	volume = {42},
	number = {4},
	year = {2017},
	month = {2017 Apr},
	pages = {568-574},
	abstract = {PURPOSE: To assess the clinical validity of visual field (VF) archetypal analysis, a previously developed machine learning method for decomposing any Humphrey VF (24-2) into a weighted sum of clinically recognizable VF loss patterns. MATERIALS AND METHODS: For each of 16 previously identified VF loss patterns ("archetypes," denoted AT1 through AT16), we screened 30,995 reliable VFs to select 10-20 representative patients whose VFs had the highest decomposition coefficients for each archetype. VF global indices and patient ocular and demographic features were extracted retrospectively. Based on resemblances between VF archetypes and clinically observed VF patterns, hypotheses were generated for associations between certain VF archetypes and clinical features, such as an association between AT6 (central island, representing severe VF loss) and large cup-to-disk ratio (CDR). Distributions of the selected clinical features were compared between representative eyes of certain archetypes and all other eyes using the two-tailed t-test or Fisher exact test. RESULTS: 243 eyes from 243 patients were included, representative of AT1 through AT16. CDR was more often >= 0.7 among eyes representative of AT6 (central island; p = 0.002), AT10 (inferior arcuate defect; p = 0.048), AT14 (superior paracentral defect; p = 0.016), and AT16 (inferior paracentral defect; p = 0.016) than other eyes. CDR was more often \&lt; 0.7 among eyes representative of AT1 (no focal defect; p \&lt; 0.001) and AT2 (superior defect; p = 0.027), which was also associated with ptosis (p \&lt; 0.001). AT12 (temporal hemianopia) was associated with history of stroke (p = 0.022). AT11 (concentric peripheral defect) trended toward association with trial lens correction \&gt; 6D (p = 0.069). CONCLUSIONS: Shared clinical features between computationally derived VF archetypes and clinically observed VF patterns support the clinical validity of VF archetypal analysis.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2016.1205630},
	author = {Cai, Sophie and Tobias Elze and Bex, Peter J and Wiggs, Janey L and Pasquale, Louis R and Shen, Lucy Q}
}
@article {1623357,
	title = {PRO score: predictive scoring system for visual outcomes after rhegmatogenous retinal detachment repair},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {555-559},
	abstract = {BACKGROUND/AIMS: To compare risk factors for poor visual outcomes in patients undergoing primary rhegmatogenous retinal detachment (RRD) repair and to develop a scoring system. METHODS: Analysis of the Primary Retinal detachment Outcomes (PRO) study, a multicentre interventional cohort of consecutive primary RRD surgeries performed in 2015. The main outcome measure was a poor visual outcome (Snellen VA <=20/200). RESULTS: A total of 1178 cases were included. The mean preoperative and postoperative logMARs were 1.1{\textpm}1.1 (20/250) and 0.5{\textpm}0.7 (20/63), respectively. Multivariable logistic regression identified preoperative risk factors predictive of poor visual outcomes (<=20/200), including proliferative vitreoretinopathy (PVR) (OR 1.26; 95\% CI 1.13 to 1.40), history of antivascular endothelial growth factor (VEGF) injections (1.38; 1.11 to 1.71), \&gt;1-week vision loss (1.17; 1.08 to 1.27), ocular comorbidities (1.18; 1.00 to 1.38), poor presenting VA (1.06 per initial logMAR unit; 1.02 to 1.10) and age \&gt;70 (1.13; 1.04 to 1.23). The data were split into training (75\%) and validation (25\%) and a scoring system was developed and validated. The risk for poor visual outcomes was 8\% with a total score of 0, 17\% with 1, 29\% with 2, 47\% with 3, and 71\% with 4 or higher. CONCLUSIONS: Independent risk factors were compared for poor visual outcomes after RRD surgery, which included PVR, anti-VEGF injections, vision loss \&gt;1 week, ocular comorbidities, presenting VA and older age. The PRO score was developed to provide a scoring system that may be useful in clinical practice.},
	keywords = {Humans, Retina, Retinal Detachment, Retrospective Studies, Scleral Buckling, Vitrectomy, Vitreoretinopathy, Proliferative, Vitreous Body},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-320440},
	author = {Cai, Louis Z and Lin, Jeffrey and Starr, Matthew R and Obeid, Anthony and Ryan, Edwin H and Ryan, Claire and Forbes, Nora J and Arias, Diego and Ammar, Michael J and Patel, Luv G and Capone, Antonio and Emerson, Geoffrey Guy and Joseph, Daniel P and Eliott, Dean and Gupta, Omesh P and Regillo, Carl D and Hsu, Jason and Yonekawa, Yoshihiro and Primary Retinal Detachment Outcomes (PRO) Study Group}
}
@article {1364587,
	title = {Mouse retinal progenitor cell dynamics on electrospun poly (ϵ-caprolactone)},
	journal = {J Biomater Sci Polym Ed},
	volume = {23},
	number = {11},
	year = {2012},
	month = {2012},
	pages = {1451-65},
	abstract = {Age-related macular degeneration, retinitis pigmentosa and glaucoma are among the many retinal degenerative diseases where retinal cell death leads to irreversible vision loss and blindness. Working toward a cell-replacement-based therapy for such diseases, a number of research groups have recently evaluated the feasibility of using retinal progenitor cells (RPCs) cultured and transplanted on biodegradable polymer substrates to replace damaged retinal tissue. Appropriate polymer substrate design is essential to providing a three-dimensional environment that can facilitate cell adhesion, proliferation and post-transplantation migration into the host environment. In this study, we have designed and fabricated a novel, ultra-thin electrospun poly(ϵ-caprolactone) (PCL) scaffold with microscale fiber diameters, appropriate porosity for infiltration by RPCs, and biologically compatible mechanical characteristics. We have verified that our electrospun PCL scaffold supports robust mouse RPC proliferation, adhesion, and differentiation in vitro, as well as migration into mouse retinal explants. These promising results make PCL a strong candidate for further development as a cell transplantation substrate in retinal regenerative research.},
	keywords = {Animals, Caproates, Cell Adhesion, Cell Culture Techniques, Cell Differentiation, Cell Movement, Lactones, Materials Testing, Mice, Inbred C57BL, Mice, Knockout, Porosity, Retina, Rhodopsin, Stem Cell Transplantation, Stem Cells, Tissue Culture Techniques, Tissue Scaffolds},
	issn = {1568-5624},
	doi = {10.1163/092050611X584388},
	author = {Cai, Sophie and Smith, Meghan Elisabeth and Redenti, Stephen Michael and Wnek, Gary Edmund and Young, Michael Joseph}
}
@article {1347430,
	title = {Thrombocytopenia is associated with severe retinopathy of prematurity},
	journal = {JCI Insight},
	volume = {3},
	number = {19},
	year = {2018},
	month = {2018 Oct 04},
	abstract = {Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (\&lt;100 {\texttimes} 109/l) at >=30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.99448},
	author = {Cakir, Bertan and Liegl, Raffael and Hellgren, Gunnel and Lundgren, Pia and Sun, Ye and Klevebro, Susanna and L{\"o}fqvist, Chatarina and Mannheimer, Clara and Cho, Steve and Poblete, Alexander and Duran, Rubi and Hallberg, Boubou and Canas, Jorge and Lorenz, Viola and Liu, Zhi-Jian and Sola-Visner, Martha C and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1538323,
	title = {IGF1, serum glucose, and retinopathy of prematurity in extremely preterm infants},
	journal = {JCI Insight},
	volume = {5},
	number = {19},
	year = {2020},
	month = {2020 Oct 02},
	abstract = {BACKGROUNDHyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood.METHODSIn 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum IGF1 levels were measured weekly. Mice with oxygen-induced retinopathy alone versus oxygen-induced retinopathy plus streptozotocin-induced hyperglycemia/hypoinsulinemia were assessed for glucose, insulin, IGF1, IGFBP1, and IGFBP3 in blood and liver. Recombinant human IGF1 was injected to assess the effect on glucose and retinopathy.RESULTSThe highest mean plasma glucose tertile of infants positively correlated with parenteral glucose intake [r(39) = 0.67, P \&lt; 0.0001]. IGF1 plasma levels were lower in the high tertile compared with those in low and intermediate tertiles at day 28 (P = 0.038 and P = 0.03). In high versus lower glucose tertiles, ROP was more prevalent (34 of 39 versus 19 of 39) and more severe (ROP stage 3 or higher; 71\% versus 32\%). In oxygen-induced retinopathy, hyperglycemia/hypoinsulinemia decreased liver IGF1 expression (P \&lt; 0.0001); rh-IGF1 treatment improved normal vascular regrowth (P = 0.027) and reduced neovascularization (P \&lt; 0.0001).CONCLUSIONIn extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased ROP severity. In a hyperglycemia retinopathy mouse model, decreased insulin signaling suppressed liver IGF1 production, lowered serum IGF1 levels, and increased neovascularization. IGF1 supplementation improved retinal revascularization and decreased pathological neovascularization. The data support IGF1 as a potential treatment for prevention of ROP.TRIAL REGISTRATIONClinicalTrials.gov NCT02760472 (Donna Mega).FUNDINGThis study has been supported by the Swedish Medical Research Council (14940, 4732, 20144-01-3, and 21144-01-3), a Swedish government grant (ALFGB2770), Lund medical faculty grants (ALFL, 11615 and 11601), the Sk{\r a}ne Council Foundation for Research and Development, the Linn{\'e}a and Josef Carlsson Foundation, the Knut and Alice Wallenberg Foundation, the NIH/National Eye Institute (EY022275, EY017017, EY017017-13S1, and P01 HD18655), European Commission FP7 project 305485 PREVENT-ROP, Deutsche Forschungsgemeinschaft (CA-1940/1-1), and Stiftelsen De Blindas V{\"a}nner.},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.140363},
	author = {Cakir, Bertan and Hellstr{\"o}m, William and Tomita, Yohei and Fu, Zhongjie and Liegl, Raffael and Winberg, Anna and Hansen-Pupp, Ingrid and Ley, David and Hellstr{\"o}m, Ann and L{\"o}fqvist, Chatarina and Smith, Lois E H}
}
@article {1364588,
	title = {Isolated unilateral linear epidermal nevus of the upper eyelid},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {28},
	number = {6},
	year = {2012},
	month = {2012 Nov-Dec},
	pages = {e135-8},
	abstract = {A 75-year-old man presented with a recurrent, unilateral, solitary, linear, corrugated lesion of the right upper eyelid of prolonged duration together with bilateral dermatochalasis. A re-excision with blepharoplasty was performed. Histopathologic analysis of the tissue revealed parallel linear arrays of papillomatosis and acanthosis with overlying basket-weave hyperkeratosis consistent with a linear epidermal nevus. Immunohistochemical studies disclosed normal numbers of intraepidermal melanocytes and Langerhans cells without Merkel cells or an increase in cycling keratinocytes. Although the term "nevus" is mostly used in conjunction with the common nevomelanocytic nevus, in fact nevi of other cutaneous cellular elements can occur on a malformational basis (such as sebaceous, eccrine, apocrine, pilar, and elastic fiber nevi). Ophthalmologists should be aware of epidermal nevi because they are rarely associated with cataracts, malignant cutaneous neoplasms, neurologic abnormalities, and musculoskeletal disorders. For focal lesions like the present one, local excision is appropriate. A select differential diagnosis of histopathologically related conditions is provided.},
	keywords = {Aged, Blepharoplasty, Eyelid Neoplasms, Humans, Langerhans Cells, Male, Melanocytes, Nevus, Sebaceous of Jadassohn, Skin Neoplasms},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e318248e66e},
	author = {Callahan, Alison B and Jakobiec, Frederick A and Zakka, Fouad R and Fay, Aaron}
}
@article {1364589,
	title = {Infantile hemangiomas: A review},
	journal = {Saudi J Ophthalmol},
	volume = {26},
	number = {3},
	year = {2012},
	month = {2012 Jul},
	pages = {283-91},
	abstract = {Infantile hemangiomas (IH) are the most common eyelid and orbital tumors of childhood. Although they are considered benign lesions that have a generally self-limited course, in the periocular region, they have the potential to cause amblyopia, strabismus, and severe disfigurement. The decision for treatment can be a source of anxiety for patients, parents, and physicians alike. There are numerous treatment modalities, including emerging therapies that may make treatment safer and more effective than ever before. This review discusses our current understanding of this disease, its management, and future therapies.},
	issn = {1319-4534},
	doi = {10.1016/j.sjopt.2012.05.004},
	author = {Callahan, Alison B and Yoon, Michael K}
}
@article {1263301,
	title = {OUTCOMES OF PARS PLANA VITRECTOMY FOR MACULAR HOLE IN PATIENTS WITH UVEITIS},
	journal = {Retina},
	volume = {38 Suppl 1},
	year = {2018},
	month = {2018 09},
	pages = {S41-S48},
	abstract = {PURPOSE: Inflammatory macular hole is a rare complication of uveitis, and data on surgical outcomes of closure are scarce. The purpose of this study is to evaluate the anatomical and visual outcomes of conventional pars plana vitrectomy for patients with uveitis. METHODS: Noncomparative, interventional, and consecutive case series from 6 vitreoretinal surgical centers from 2007 to 2015. Twenty eyes of 19 patients were included with 4 patients separated as viral retinitis. The primary outcome was change in best-corrected visual acuity at Month 3. Secondary outcomes were closure of the macular hole and postoperative optical coherence tomography characteristics. RESULTS: All eyes underwent conventional three-port pars plana vitrectomy with indocyanine green-assisted internal limiting membrane peeling. Mean Snellen best-corrected visual acuity improved from 20/200 to 20/63 (P = 0.01 for a difference in logarithm of the minimum angle of resolution) at Month 3. Twelve (75\%) of patients achieved 2 or more lines of visual acuity improvement by postoperative Month 3. Surgery resulted in decreased epiretinal membrane (P = 0.002), intraretinal fluid (P \&lt; 0.001), subretinal fluid (P = 0.029), central subfield thickness (P \&lt; 0.001), and central cube volume (P = 0.041). Surgical intervention achieved anatomical success, as measured by macular hole closure, in 13 (81\%) of patients at postoperative Month 3. CONCLUSION: Patients with inflammatory macular hole respond well to conventional surgery, with good anatomical and visual acuity outcomes.},
	keywords = {Adult, Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retinal Perforations, Retrospective Studies, Time Factors, Tomography, Optical Coherence, Treatment Outcome, Uveitis, Visual Acuity, Vitrectomy},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001942},
	author = {Callaway, Natalia F and Gonzalez, Marco A and Yonekawa, Yoshihiro and Faia, Lisa J and Mandelcorn, Efrem D and Khurana, Rahul N and Saleh, Mohamed G A and Lin, Phoebe and Sobrin, Lucia and Albini, Thomas A}
}
@article {280876,
	title = {Bilateral Sequential Dacryocystitis in a Patient With Graft-Versus-Host Disease.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {4},
	year = {2016},
	month = {2016 Jul-Aug},
	pages = {e89-92},
	abstract = {A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens. Histopathologic and immunohistochemical examination of the lacrimal sac showed a dense diffuse nonfollicular lymphocytic subepithelial infiltrate in the lacrimal sac that contained moderately more T-cells than B-cells. This is the first report of acute dacryocystitis associated with graft-versus-host disease. The authors caution that similar patients may develop worsening of ocular surface dryness due to restoration of normal lacrimal outflow.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000267},
	author = {Campbell, Ashley A and Jakobiec, Frederick A and Rashid, Alia and Dana, Reza and Yoon, Michael K}
}
@article {541311,
	title = {Spontaneous Resorption of a Penetrating Orbital Bone Fracture Fragment.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {5},
	year = {2015},
	month = {2015 Sep-Oct},
	pages = {e123-5},
	abstract = {The authors describe a 20-year-old man who sustained multiple facial fractures in a high-speed motor vehicle crash, including a bone fragment from a skull base fracture that penetrated the orbital soft tissues superomedially. Serial CT scans documented spontaneous resorption over a 6-month period. While it is known that autologous bone grafts used in craniofacial reconstruction exhibit variable amounts of bone resorption, the complete resorption of an intraorbital fracture fragment has not been documented in the literature. His clinical care and the report of his case were undertaken in a fashion in accordance with the principles of the Health Insurance Portability and Accountability Act regulations.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000146},
	author = {Campbell, Ashley A and Cunnane, Mary Elizabeth and Dunn, Gavin P and Gray, Stacy Tutt and Lefebvre, Daniel R}
}
@article {630241,
	title = {Rituximab in the Treatment of Refractory Noninfectious Scleritis.},
	journal = {Am J Ophthalmol},
	volume = {164},
	year = {2016},
	month = {2016 Apr},
	pages = {22-8},
	abstract = {PURPOSE: To describe the outcomes of the use of rituximab in the treatment of refractory noninfectious scleritis. DESIGN: Retrospective case series. METHODS: Review of the medical charts of patients with noninfectious scleritis refractory to conventional immunomodulatory therapy who were seen at the Massachusetts Eye Research and Surgery Institution between 2005 and 2015. The primary outcome measure in this study was steroid-free remission. Secondary outcomes were favorable response (decrease in scleritis activity score) and decrease in steroid dependence. RESULTS: There were 15 patients, with a mean follow-up duration of 34\&nbsp;months. Fourteen patients (93.3\%) showed a clinical improvement, with 13 (86.6\%) achieving a scleritis activity score of zero at 6\&nbsp;months. To date, 2 patients continue to enjoy durable drug-free remission (28 and 32\&nbsp;months follow-up). There was only 1 adverse effect recorded (infusion hypotension) requiring cessation of rituximab. CONCLUSION: Rituximab can be an effective treatment modality for recalcitrant noninfectious scleritis and, in some, can result in long-term durable drug-free remission.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.12.032},
	author = {Cao, Jennifer H and Oray, Merih and Cocho, Lidia and Foster, C Stephen}
}
@article {1302175,
	title = {HLA Class I Antigen Expression in Conjunctival Melanoma Is Not Associated With PD-L1/PD-1 Status},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {2},
	year = {2018},
	month = {2018 Feb 01},
	pages = {1005-1015},
	abstract = {Purpose: Antitumor T cells need expression of HLA class I molecules but can be inhibited by ligands such as programmed death ligand 1 (PD-L1). We determined expression and regulation of these molecules in human conjunctival melanoma (CM) samples, cell lines, and murine xenografts. Methods: Immunofluorescence staining was performed to examine the expression of HLA-A, HLA-B/C, and β-2-microglobulin (B2M) in 23 primary CM samples. HLA class I expression was compared with clinicopathologic characteristics, the presence of tumor-infiltrating leukocytes, and PD-L1/PD-1 status. The effect of interferon γ (IFN-γ) on HLA class I expression was tested on three CM cell lines using quantitative PCR and flow cytometry. Furthermore, HLA class I expression was determined in CM cell line-derived murine xenografts. Results: One third of tumors had positive HLA-A, HLA-B/C, and B2M expression. A positive expression was especially seen in thin and epibulbar tumors but was not associated with recurrences. HLA class I expression was correlated with M2 macrophage density and tended to associate with CD8+ T-cell density but was independent of PD-L1 or PD-1 expression. IFN-γ upregulated HLA class I expression and genes involved in HLA transcription and transportation on CM cell lines. Murine xenografts showed a comparable HLA class I expression as their respective cell lines. Conclusions: Our data indicate that subsets of CM have positive HLA class I expression, and HLA class I and PD-L1/PD-1 are expressed independently. When one considers immunotherapy, one should also analyze HLA class I expression, whose downregulation can limit the efficacy of T cell-mediated therapies.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-23209},
	author = {Cao, Jinfeng and Brouwer, Niels J and Jordanova, Ekaterina S and Marinkovic, Marina and van Duinen, Sjoerd G and de Waard, Nadine E and Ksander, Bruce R and Mulder, Arend and Claas, Frans H J and Heemskerk, Mirjam H M and Jager, Martine J}
}
@article {1589742,
	title = {Septic cavernous sinus thrombosis: A review},
	journal = {Surv Ophthalmol},
	volume = {66},
	number = {6},
	year = {2021},
	month = {2021 Nov-Dec},
	pages = {1021-1030},
	abstract = {Septic cavernous sinus thrombosis (SCST) is a rare, yet severe, process typically arising from infections of the paranasal sinuses (predominately ethmoid and/or sphenoid sinusitis) and less commonly, otogenic, odontogenic, and pharyngeal sources. Clinical symptoms of SCST arise from obstruction of venous drainage from the orbit and compression of the cranial nerves within the cavernous sinus. In the preantibiotic era SCST was considered universally fatal (80-100\%); however, with the introduction of antibiotics the overall incidence, morbidity, and mortality of SCST have greatly declined. In spite of dramatic improvements, morbidity and mortality remain high, with the majority of patients experiencing neurological sequalae, highlighting the severity of the disease and the need for prompt recognition, diagnosis, and treatment. Here we review of the literature on SCST with a focus on the current recommendations and recent evidence for diagnostic and medical management of this condition.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2021.03.009},
	author = {Caranfa, Jonathan T and Yoon, Michael K}
}
@article {1623376,
	title = {Comments on "Initial clinical manifestation of multiple sclerosis after immunization with the Pfizer-BioNTech COVID-19 vaccine" by , J Neuroimmunol},
	journal = {J Neuroimmunol},
	volume = {362},
	year = {2022},
	month = {2022 01 15},
	pages = {577780},
	keywords = {BNT162 Vaccine, COVID-19, COVID-19 Vaccines, Humans, Immunization, Multiple Sclerosis, SARS-CoV-2},
	issn = {1872-8421},
	doi = {10.1016/j.jneuroim.2021.577780},
	author = {Caravagna, C{\'e}line}
}
@article {1667711,
	title = {Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G\&gt;A MT-ND4 Mutation},
	journal = {Ophthalmol Ther},
	volume = {12},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {401-429},
	abstract = {INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G\&gt;A ND4 mutation (MT-ND4). A previous pooled analysis of phase\&nbsp;3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase\&nbsp;3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174. METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase\&nbsp;3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies. RESULTS: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P \&lt; 0.01) with a maximal follow-up of 3.9\&nbsp;years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48\&nbsp;months after vision loss (89.6\% versus 48.1\%; P \&lt; 0.01) and at last observation (76.1\% versus 44.4\%; P \&lt; 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was -\&nbsp;0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P \&lt; 0.0001). Treatment effect was consistent across all phase\&nbsp;3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection. CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection. TRIAL REGISTRATION NUMBERS: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY).},
	issn = {2193-8245},
	doi = {10.1007/s40123-022-00611-x},
	author = {Carelli, Valerio and Newman, Nancy J and Yu-Wai-Man, Patrick and Biousse, Valerie and Moster, Mark L and Subramanian, Prem S and Vignal-Clermont, Catherine and Wang, An-Guor and Donahue, Sean P and Leroy, Bart P and Sergott, Robert C and Klopstock, Thomas and Sadun, Alfredo A and Fern{\'a}ndez, Gema Rebolleda and Chwalisz, Bart K and Banik, Rudrani and Girmens, Jean Fran{\c c}ois and La Morgia, Chiara and DeBusk, Adam A and Jurkute, Neringa and Priglinger, Claudia and Karanjia, Rustum and Josse, Constant and Salzmann, Julie and Montestruc, Fran{\c c}ois and Roux, Michel and Taiel, Magali and Sahel, Jos{\'e}-Alain and the~LHON Study Group}
}
@article {1351142,
	title = {Discovery and functional annotation of SIX6 variants in primary open-angle glaucoma},
	journal = {PLoS Genet},
	volume = {10},
	number = {5},
	year = {2014},
	month = {2014},
	pages = {e1004372},
	abstract = {Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87{\texttimes}10(-11)). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2{\texttimes}10(-10)) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss.},
	keywords = {Aged, Alleles, Chromosomes, Human, Pair 9, Eye, Female, Genome-Wide Association Study, Glaucoma, Open-Angle, Homeodomain Proteins, Humans, Intraocular Pressure, Optic Nerve, Trans-Activators},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1004372},
	author = {Carnes, Megan Ulmer and Liu, Yangfan P and Allingham, R Rand and Whigham, Benjamin T and Havens, Shane and Garrett, Melanie E and Qiao, Chunyan and NEIGHBORHOOD Consortium Investigators and Katsanis, Nicholas and Wiggs, Janey L and Pasquale, Louis R and Ashley-Koch, Allison and Oh, Edwin C and Hauser, Michael A}
}
@article {931036,
	title = {Clinical Presentation and Bacteriology of Eyebrow Infections: The Massachusetts Eye and Ear Infirmary Experience (2008-2015)},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {5},
	year = {2017},
	month = {2017 Sep/Oct},
	pages = {372-375},
	abstract = {PURPOSE: This study retrospectively reviews preseptal cellulitis and abscesses involving the eyebrow to elucidate the bacteriology and potential causative factors. METHODS: A retrospective chart review was conducted to identify patients who had been diagnosed with preseptal cellulitis or abscess involving the eyebrow at the Massachusetts Eye and Ear Infirmary between 2008 and 2015. Demographic, clinical, and microbiological data were collected. RESULTS: Eighty patients with eyebrow infections were identified, of whom 49 (61.3\%) were female and 31 (38.7\%) were male. The median age was 37 years (range 14-67 years). Eyebrow abscess was present in 54 cases (67.5\%), while 26 cases (32.5\%) were limited to preseptal cellulitis without abscess formation. Methicillin-resistant Staphylococcus aureus was found in 20 abscesses (39.2\% of culture results), and methicillin-sensitive S. aureus was found in 12 abscesses (23.5\% of culture results). Coagulase-negative staphylococci were present in 7 eyebrow abscesses (13.7\% of culture results). Clinical history was remarkable for eyebrow hair removal (tweezing, waxing, threading, or shaving) in 17 cases (21.3\%), manipulation of acne lesions ("popping," "picking," or "squeezing") in 6 cases (7.5\%), and both brow hair removal and acne manipulation in 1 case (1.3\%). CONCLUSIONS: There is a high incidence of methicillin-resistant Staphylococcus aureus in the bacteriology of eyebrow infections. Empirical antibiotic coverage for methicillin-resistant Staphylococcus aureus should be strongly considered in any patient with an eyebrow area abscess or preseptal cellulitis. Individuals who practice cosmetic eyebrow grooming should be encouraged to consider hygiene practices, which could reduce the risk of infection.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000797},
	author = {Carniciu, Ana{\"\i}s L and Chou, Jonathan and Leskov, Ilya and Freitag, Suzanne K}
}
@article {1466919,
	title = {Clinical and radiologic approach to {\textquoteright}typical{\textquoteright} versus antibody-related optic neuritis},
	journal = {Curr Opin Ophthalmol},
	volume = {30},
	number = {6},
	year = {2019},
	month = {2019 Nov},
	pages = {412-417},
	abstract = {PURPOSE OF REVIEW: Optic neuritis is an autoimmune optic neuropathy that has been associated with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and more recently antimyelin oligodendrocyte glycoprotein (anti-MOG)-positive disorder. At initial presentation, it is often difficult to differentiate these entities given their significant overlap in clinical presentation and MRI findings. This review summarizes the distinguishing clinical and radiological features of MS, NMOSD, and anti-MOG disorders to help clinicians accurately diagnose and manage patients affected by these conditions. RECENT FINDINGS: Antiaquaporin-4 (AQP4) and more recently anti-MOG antibodies are both associated with central nervous system demyelinating diseases that often initially present with optic neuritis. Serologic testing now allows for a new classification of these overlapping conditions that can help to differentiate {\textquoteright}typical{\textquoteright} optic neuritis that is often associated with MS from {\textquoteright}atypical{\textquoteright} optic neuritis associated with NMOSD and anti-MOG-positive disorder. SUMMARY: Optic neuritis associated with MS, NMOSD, and anti-MOG-positive disease can have a similar clinical presentation. However, some clinical and radiologic findings can help clinicians to differentiate these entities so that they can be properly managed to optimize visual prognosis.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000614},
	author = {Caron-Cantin, Marilou and Cestari, Dean M and Fortin, Elizabeth}
}
@article {1538331,
	title = {Limbal Stem Cell Deficiency Associated With Herpes Keratitis},
	journal = {Cornea},
	volume = {40},
	number = {8},
	year = {2021},
	month = {2021 Aug 01},
	pages = {967-971},
	abstract = {PURPOSE: To describe the demographic features and clinical characteristics of patients with herpes keratitis (HK) and limbal stem cell deficiency (LSCD) and identify possible factors associated with development of LSCD after HK. METHODS: In this retrospective case-series study, records of patients with a clinical diagnosis of HK seen at Massachusetts Eye and Ear over a 5-year period were reviewed for evidence of LSCD. Patient demographics, medical history, treatment, and best-corrected visual acuities (BCVAs) were recorded. RESULTS: We identified 626 patients with HK. Fifty-seven had been diagnosed with LSCD (9.3\%). Thirteen percent of patients with herpes zoster keratitis (N= 25) and 7\% of patients with herpes simplex keratitis (N= 32) had LSCD (P = 0.01). Keratitis caused by herpes zoster virus [odds ratios (OR), 1.77; 95\% confidence interval (CI), 0.97-3.19; P = 0.01], stromal involvement (OR, 2.28; 95\% CI, 1.27-4.18; P = 0.02), and the use of topical antihypertensives (OR, 2.28; 95\% CI, 1.27-4.18; P = 0.02) were found to be associated with a higher likelihood of developing LSCD. The final logarithm of the minimum angle of resolution (LogMAR) BCVA was significantly lower in patients with LSCD compared with those without LSCD with a mean BCVA of 1.34 {\textpm} 1.52 LogMar (\~{}20/200) as compared to 0.18 {\textpm} 0.54 LogMar (\~{}20/30 {\textpm} 20/60) in those patients without LSCD (P = 0.005). CONCLUSIONS: Our data suggest that HK may be a risk factor for development of LSCD. Patients with HK should be monitored for the development of LSCD to reduce the risk of chronic ocular surface morbidity.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002557},
	author = {Carreno-Galeano, Jimena Tatiana and Dohlman, Thomas H and Yin, Jia and Dana, Reza}
}
@article {1664980,
	title = {Autologous serum tears improve corneal nerve density and sensitivity in patients with ocular graft-versus-host disease-associated dry eye disease},
	journal = {Ocul Surf},
	year = {2023},
	month = {2023 Jan 20},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2023.01.004},
	author = {Carreno-Galeano, Jimena Tatiana and Johns, Lynette K and Dana, Reza and Yin, Jia}
}
@article {1603854,
	title = {A Review of Ocular Graft-versus-Host Disease: Pathophysiology, Clinical Presentation and Management},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Jul 06},
	pages = {1-10},
	abstract = {Graft-versus-host disease is a common complication following allogeneic hematopoetic stem cell transplantation that can affect multiple organ systems, including the eyes. Ocular GVHD (oGVHD) is characterized by a T cell-mediated immune response that leads to immune cell infiltration and inflammation of ocular structures, including the lacrimal glands, eyelids, cornea and conjunctiva. oGVHD has a significant negative impact on visual function and quality of life and successful management requires a multi-disciplinary approach with frequent monitoring. Here, we review the pathophysiology and clinical presentation of oGVHD, along with current therapeutic strategies based on our clinical experience and the reported literature.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2021.1939390},
	author = {Carreno-Galeano, Jimena Tatiana and Dohlman, Thomas H and Kim, Stella and Yin, Jia and Dana, Reza}
}
@article {603841,
	title = {Understanding Cone Photoreceptor Cell Death in Achromatopsia.},
	journal = {Adv Exp Med Biol},
	volume = {854},
	year = {2016},
	month = {2016},
	pages = {231-6},
	abstract = {Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.},
	issn = {0065-2598},
	doi = {10.1007/978-3-319-17121-0_31},
	author = {Carvalho, Livia S and Vandenberghe, Luk H}
}
@article {284031,
	title = {Promising and delivering gene therapies for vision loss},
	journal = {Vision Res},
	volume = {111},
	number = {Pt B},
	year = {2015},
	month = {2015 Jun},
	pages = {124-33},
	abstract = {The maturity in our understanding of the genetics and the pathogenesis of disease in degenerative retinal disorders has intersected in past years with a novel treatment paradigm in which a genetic intervention may lead to sustained therapeutic benefit, and in some cases even restoration of vision. Here, we review this prospect of retinal gene therapy, discuss the enabling technologies that have led to first-in-human demonstrations of efficacy and safety, and the road that led to this exciting point in time.},
	keywords = {Blindness, Clinical Trials as Topic, Dependovirus, Gene Transfer Techniques, Genetic Therapy, Humans, Retinal Degeneration},
	issn = {1878-5646},
	doi = {10.1016/j.visres.2014.07.013},
	author = {Carvalho, Livia S and Vandenberghe, Luk H}
}
@article {1295854,
	title = {Synthetic Adeno-Associated Viral Vector Efficiently Targets Mouse and Nonhuman Primate Retina In Vivo},
	journal = {Hum Gene Ther},
	volume = {29},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {771-784},
	abstract = {Gene therapy is a promising approach in the treatment of inherited and common complex disorders of the retina. Preclinical and clinical studies have validated the use of adeno-associated viral vectors (AAV) as a safe and efficient delivery vehicle for gene transfer. Retinal pigment epithelium and rods-and to a lesser extent, cone photoreceptors-can be efficiently targeted with AAV. Other retinal cell types however are more challenging targets. The aim of this study was to characterize the transduction profile and efficiency of in silico designed, synthetic Anc80 AAVs for retinal gene transfer. Three Anc80 variants were evaluated for retinal targeting in mice and primates following subretinal delivery. In the murine retina Anc80L65 demonstrated high level of retinal pigment epithelium and photoreceptor targeting with comparable cone photoreceptor affinity compared to other AAVs. Remarkably, Anc80L65 enhanced transduction kinetics with visible expression as early as day 1 and steady state mRNA levels at day 3. Inner retinal tropism of Anc80 variants demonstrated distinct transduction patterns of M{\"u}ller glia, retinal ganglion cells and inner nuclear layer neurons. Finally, murine findings with Anc80L65 qualitatively translated to the Rhesus macaque in terms of cell targets, levels and onset of expression. Our findings support the use of Anc80L65 for therapeutic subretinal gene delivery.},
	issn = {1557-7422},
	doi = {10.1089/hum.2017.154},
	author = {Carvalho, Livia S and Xiao, Ru and Wassmer, Sarah J and Langsdorf, Aliete and Zinn, Eric and Pacouret, Simon and Shah, Samiksha and Comander, Jason I and Kim, Leo A and Lim, Laurence and Vandenberghe, Luk H}
}
@article {1782276,
	title = {Reply},
	journal = {Ophthalmol Glaucoma},
	volume = {7},
	number = {2},
	year = {2024},
	month = {2024 Mar-Apr},
	pages = {216-217},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2023.11.001},
	author = {Castillejos, Alexandra G and Devlin, Julia and Saini, Chhavi and Sun, Jessica A and Wang, Mengyu and Johnson, Grace and Chodosh, James and Shen, Lucy Q}
}
@article {603851,
	title = {Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids.},
	journal = {Methods Mol Biol},
	volume = {1382},
	year = {2016},
	month = {2016},
	pages = {133-49},
	abstract = {More than one hundred naturally occurring variants of adeno-associated virus (AAV) have been identified, and this library has been further expanded by an array of techniques for modification of the viral capsid. AAV capsid variants possess unique antigenic profiles and demonstrate distinct cellular tropisms driven by differences in receptor binding. AAV capsids can be chemically modified to alter tropism, can be produced as hybrid vectors that combine the properties of multiple serotypes, and can carry peptide insertions that introduce novel receptor-binding activity. Furthermore, directed evolution of shuffled genome libraries can identify engineered variants with unique properties, and rational modification of the viral capsid can alter tropism, reduce blockage by neutralizing antibodies, or enhance transduction efficiency. This large number of AAV variants and engineered capsids provides a varied toolkit for gene delivery to the CNS and retina, with specialized vectors available for many applications, but selecting a capsid variant from the array of available vectors can be difficult. This chapter describes the unique properties of a range of AAV variants and engineered capsids, and provides a guide for selecting the appropriate vector for specific applications in the CNS and retina.},
	issn = {1940-6029},
	doi = {10.1007/978-1-4939-3271-9_10},
	author = {Castle, Michael J and Turunen, Heikki T and Vandenberghe, Luk H and Wolfe, John H}
}
@article {1603837,
	title = {Approaches for corneal endothelium regenerative medicine},
	journal = {Prog Retin Eye Res},
	volume = {87},
	year = {2022},
	month = {2022 Mar},
	pages = {100987},
	abstract = {The state of the art therapy for treating corneal endothelial disease is transplantation. Advances in the reproducibility and accessibility of surgical techniques are increasing the number of corneal transplants, thereby causing a global deficit of donor corneas and leaving 12.7 million patients with addressable visual impairment. Approaches to regenerate the corneal endothelium offer a solution to the current tissue scarcity and a treatment to those in need. Methods for generating corneal endothelial cells into numbers that could address the current tissue shortage and the possible strategies used to deliver them have now become a therapeutic reality with clinical trials taking place in Japan, Singapore and Mexico. Nevertheless, there is still a long way before such therapies are approved by regulatory bodies and become clinical practice. Moreover, acellular corneal endothelial graft equivalents and certain drugs could provide a treatment option for specific disease conditions without the need of donor tissue or cells. Finally, with the emergence of gene modulation therapies to treat corneal endothelial disease, it would be possible to treat presymptomatic patients or those presenting early symptoms, drastically reducing the need for donor tissue. It is necessary to understand the most recent developments in this rapidly evolving field to know which conditions could be treated with which approach. This article provides an overview of the current and developing regenerative medicine therapies to treat corneal endothelial disease and provides the necessary guidance and understanding towards the treatment of corneal endothelial disease.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2021.100987},
	author = {Catal{\`a}, Pere and Thuret, Gilles and Skottman, Heli and Mehta, Jodhbir S and Parekh, Mohit and N{\'\i} Dhubhghaill, Sorcha and Collin, Rob W J and Nuijts, Rudy M M A and Ferrari, Stefano and LaPointe, Vanessa L S and Dickman, Mor M}
}
@article {1629462,
	title = {Novel RCBTB1 variants causing later-onset non-syndromic retinal dystrophy with macular chorioretinal atrophy},
	journal = {Ophthalmic Genet},
	volume = {43},
	number = {3},
	year = {2022},
	month = {2022 Jun},
	pages = {332-339},
	abstract = {BACKGROUND: Variants in RCBTB1 were recently described to cause a retinal dystrophy with only eight families described to date and a predominant phenotype of macular atrophy and peripheral reticular degeneration. Here, we further evaluate the genotypic and phenotypic characteristics of biallelic RCBTB1-associated retinal dystrophy in a North American clinic population. METHODS: A retrospective analysis of genetic and clinical features was performed in individuals with biallelic variants in RCBTB1. RESULTS: Three unrelated individuals of French-Canadian descent with rare biallelic RCBTB1 variants were identified. All individuals shared a novel p.(Ser342Leu) missense variant; one patient was homozygous whereas the other two each possessed a second unique novel variant p.(Gln120*) and p.(Pro224Leu). All three had macula-predominant disease with symptom onset in the fifth decade of life. CONCLUSION: This report adds to the genetic diversity of RCBTB1-associated disease. These cases confirm the later-onset, relative to many other retinal dystrophies, and macular focus of disease described in most cases to-date. They are thus a reminder of considering hereditary disease in the differential for later-onset macular atrophy.},
	keywords = {Atrophy, Canada, Guanine Nucleotide Exchange Factors, Humans, Macular Degeneration, Pedigree, Phenotype, Retinal Dystrophies, Retrospective Studies},
	issn = {1744-5094},
	doi = {10.1080/13816810.2021.2023196},
	author = {Catomeris, Andrew J and Ballios, Brian G and Sangermano, Riccardo and Wagner, Naomi E and Comander, Jason I and Pierce, Eric A and Place, Emily M and Bujakowska, Kinga M and Huckfeldt, Rachel M}
}
@article {1511510,
	title = {Optic Neuropathy Due to Compression by an Ectatic Internal Carotid Artery Within the Orbital Apex},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {1},
	year = {2021},
	month = {2021 Mar 01},
	pages = {e103-e104},
	abstract = {ABSTRACT: Neurovascular compression is a rare but potentially treatable cause of optic neuropathy. Although incidental contact of the cisternal optic nerve and internal carotid artery (ICA) is common, compressive optic neuropathy occurring within the orbital apex has not been comprehensively described. We report a case of intra-orbital and intracanalicular optic nerve compression due to an ectatic ICA in a patient with congenital absence of the contralateral ICA. This report describes the complementary roles of advanced neuroimaging and neuro-ophthalmologic examination in rendering the diagnosis.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000975},
	author = {Caton, Michael T and Zamani, Amir A and Du, Rose and Prasad, Sashank}
}
@article {303981,
	title = {The role of prefrontal and parietal cortices in esthetic appreciation of representational and abstract art: a TMS study},
	journal = {Neuroimage},
	volume = {99},
	year = {2014},
	month = {2014 Oct 01},
	pages = {443-50},
	abstract = {To explain the biological foundations of art appreciation is to explain one of our species{\textquoteright} distinctive traits. Previous neuroimaging and electrophysiological studies have pointed to the prefrontal and the parietal cortex as two critical regions mediating esthetic appreciation of visual art. In this study, we applied transcranial magnetic stimulation (TMS) over the left prefrontal cortex and the right posterior parietal cortex while participants were evaluating whether they liked, and by how much, a particular painting. By depolarizing cell membranes in the targeted regions, TMS transiently interferes with the activity of specific cortical areas, which allows clarifying their role in a given task. Our results show that both regions play a fundamental role in mediating esthetic appreciation. Critically though, the effects of TMS varied depending on the type of art considered (i.e. representational vs. abstract) and on participants{\textquoteright} a-priori inclination toward one or the other.},
	keywords = {Adult, Art, Esthetics, Female, Humans, Male, Parietal Lobe, Photic Stimulation, Prefrontal Cortex, Reaction Time, Transcranial Magnetic Stimulation, Young Adult},
	issn = {1095-9572},
	doi = {10.1016/j.neuroimage.2014.05.037},
	author = {Cattaneo, Zaira and Lega, Carlotta and Gardelli, Chiara and Merabet, Lotfi B and Cela-Conde, Camilo J and Nadal, Marcos}
}
@article {1302165,
	title = {The Spatial Musical Association of Response Codes does not depend on a normal visual experience: A study with early blind individuals},
	journal = {Atten Percept Psychophys},
	volume = {80},
	number = {4},
	year = {2018},
	month = {2018 May},
	pages = {813-821},
	abstract = {Converging evidence suggests that the perception of auditory pitch exhibits a characteristic spatial organization. This pitch-space association can be demonstrated experimentally by the Spatial Musical Association of Response Codes (SMARC) effect. This is characterized by faster response times when a low-positioned key is pressed in response to a low-pitched tone, and a high-positioned key is pressed in response to a high-pitched tone. To investigate whether the development of this pitch-space association is mediated by normal visual experience, we tested a group of early blind individuals on a task that required them to discriminate the timbre of different instrument sounds with varying pitch. Results revealed a comparable pattern in the SMARC effect in both blind participants and sighted controls, suggesting that the lack of prior visual experience does not prevent the development of an association between pitch height and vertical space.},
	issn = {1943-393X},
	doi = {10.3758/s13414-018-1495-x},
	author = {Cattaneo, Zaira and Lega, Carlotta and Rinaldi, Luca and Fantino, Micaela and Ferrari, Chiara and Merabet, Lotfi B and Vecchi, Tomaso}
}
@article {1179126,
	title = {In vivo confocal microscopy detects bilateral changes of corneal immune cells and nerves in unilateral herpes zoster ophthalmicus},
	journal = {Ocul Surf},
	volume = {16},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {101-111},
	abstract = {PURPOSE: To analyze bilateral corneal immune cell and nerve alterations in patients with unilateral herpes zoster ophthalmicus (HZO) by laser in\&nbsp;vivo confocal microscopy (IVCM) and their correlation with corneal sensation and clinical findings. MATERIALS AND METHODS: This is a prospective, cross-sectional, controlled, single-center study. Twenty-four eyes of 24 HZO patients and their contralateral clinically unaffected eyes and normal controls (n\&nbsp;=\&nbsp;24) were included. Laser IVCM (Heidelberg Retina Tomograph/Rostock Cornea Module), corneal esthesiometry (Cochet-Bonnet) were performed. Changes in corneal dendritiform cell (DC) density and morphology, number and length of subbasal nerve fibers and their correlation to corneal sensation, pain, lesion location, disease duration, and number of episodes were analyzed. RESULTS: HZO-affected and contralateral eyes showed a significant increase in DC influx of the central cornea as compared to controls (147.4\&nbsp;{\textpm}\&nbsp;33.9, 120.1\&nbsp;{\textpm}\&nbsp;21.2, and 23.0\&nbsp;{\textpm}\&nbsp;3.6\&nbsp;cells/mm2; p\&nbsp;\&lt;\&nbsp;0.0001). In HZO eyes DCs were larger in area (319.4\&nbsp;{\textpm}\&nbsp;59.8\&nbsp;μm2; p\&nbsp;\&lt;\&nbsp;0.001) and number of dendrites (3.5\&nbsp;{\textpm}\&nbsp;0.4 n/cell; p\&nbsp;=\&nbsp;0.01) as compared to controls (52.2\&nbsp;{\textpm}\&nbsp;11.7, and 2.3\&nbsp;{\textpm}\&nbsp;0.5). DC density and size showed moderate negative correlation with total nerve length (R\&nbsp;=\&nbsp;-0.43 and R\&nbsp;=\&nbsp;-0.57, respectively; all p\&nbsp;\&lt;\&nbsp;0.001). A higher frequency of nerve beading and activated DCs close to nerve fibers were detected specifically in pain patients. CONCLUSIONS: Chronic unilateral HZO causes significant bilateral increase in corneal DC density and decrease of the corneal subbasal nerves as compared to controls. Negative correlation was observed for DC density and size to nerve parameters, suggesting interplay between the immune and nervous systems. Patients with chronic pain also showed increased nerve beading and activated DCs.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.09.004},
	author = {Cavalcanti, Bernardo M and Cruzat, Andrea and Sahin, Afsun and Pavan-Langston, Deborah and Samayoa, Eric and Hamrah, Pedram}
}
@article {1761861,
	title = {Genetic testing for infantile nystagmus syndrome with or without associated findings},
	journal = {J AAPOS},
	volume = {27},
	number = {5},
	year = {2023},
	month = {2023 Oct},
	pages = {259-264},
	abstract = {PURPOSE: To review the published literature assessing the clinical utility of genetic testing in individuals with infantile nystagmus syndrome (INS), defined as binocular conjugate nystagmus and onset prior to 6 months of age, with or without associated findings. METHODS: A literature search was last conducted in October 2022. The results were limited to articles published in English. The search yielded 517 abstracts, of which 72 papers were reviewed in full text. Of these papers, 4 met the criteria for inclusion and were graded by a study methodologist. RESULTS: The 4 studies that met inclusion criteria used next-generation sequencing with gene panels ranging from 31 to 336 genes. The overall molecular diagnostic rate ranged from 35\% to 60\% in the included studies, although the yield was higher when genetic testing was guided by clinical phenotyping (approximately 80\%) and in the subsets of patients with a family history (up to 88\%). As many as 30\% of patients tested had a reclassification of the diagnosis based on the genetic testing results. CONCLUSIONS: Genetic testing has the potential to provide a definitive diagnosis and identify treatable conditions in patients presenting with INS, especially when considered in conjunction with clinical phenotyping and family history.},
	keywords = {Genetic Testing, Humans, Nystagmus, Pathologic},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.07.007},
	author = {Cavuoto, Kara M and Binenbaum, Gil and Chang, Melinda Y and Heidary, Gena and Morrison, David G and Trivedi, Rupal H and Kim, Stephen J and Pineles, Stacy L}
}
@article {1658666,
	title = {Effectiveness of Laser Refractive Surgery to Address Anisometropic Amblyogenic Refractive Error in Children: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {129},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {1323-1331},
	abstract = {PURPOSE: To review the published literature assessing the safety and effectiveness of laser refractive surgery to treat anisometropic amblyogenic refractive error in children aged <= 18 years. METHODS: A literature search of the PubMed database was conducted in October 2021 with no date limitations and restricted to publications in English. The search yielded 137 articles, 69 of which were reviewed in full text. Eleven articles met the criteria for inclusion and were assigned a level of evidence rating. RESULTS: The 11 included articles were all level III evidence and consisted of 1 case-control study and 10 case series. Six studies used laser-assisted in situ keratomileusis (LASIK), 1 used photorefractive keratectomy (PRK), 1 used refractive lenticule extraction/small incision lenticule extraction, and the rest used a combination of LASIK, PRK, laser epithelial keratomileusis (LASEK), or refractive lenticule extraction/small incision lenticule extraction. Five studies enrolled patients with anisometropic myopia, 2 studies enrolled patients with anisometropic hyperopia, and the remainder were mixed. Although all studies demonstrated an improvement in best-corrected visual acuity (BCVA), the magnitude of improvement varied widely. As study parameters varied, a successful outcome was defined as residual refractive error of 1 diopter (D) or less of the target refraction because this was the most commonly used metric. Successful outcomes ranged between 38\% and 87\%, with a mean follow-up ranging from 4 months to 7 years. Despite this wide range, all studies demonstrated an improvement in the magnitude of anisometropia. Regression in refractive error occurred more frequently and to a greater degree in myopic eyes and eyes with longer follow-up, and in younger patients. Although one study reported 2 free flaps, most studies reported no serious adverse events. The most common complications were corneal haze and striae. CONCLUSIONS: Findings from included studies suggest that laser refractive surgery may address amblyogenic refractive error in children and that it appears to decrease anisometropia. However, the evidence for improvement in amblyopia is unclear and long-term safety data are lacking. Long-term data and well-designed clinical studies that use newer refractive technologies in standardized patient populations would help address the role of refractive surgery in children and its potential impact on amblyopia.},
	keywords = {Amblyopia, Anisometropia, Case-Control Studies, Child, Cornea, Humans, Lasers, Excimer, Myopia, Ophthalmology, Photorefractive Keratectomy, Visual Acuity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.06.022},
	author = {Cavuoto, Kara M and Chang, Melinda Y and Heidary, Gena and Morrison, David G and Trivedi, Rupal H and Binenbaum, Gil and Kim, Stephen J and Pineles, Stacy L}
}
@article {1593855,
	title = {Structure-Function Mapping Using a Three-Dimensional Neuroretinal Rim Parameter Derived From Spectral Domain Optical Coherence Tomography Volume Scans},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {6},
	year = {2021},
	month = {2021 May 03},
	pages = {28},
	abstract = {Purpose: To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans. Methods: Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch{\textquoteright}s membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength. Results: The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20). Conclusions: Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.6.28},
	author = {Celebi, Ali Riza Cenk and Park, Elli A and Verticchio Vercellin, Alice Chandra and Tsikata, Edem and Lee, Ramon and Shieh, Eric and Antar, Hussein and Freeman, Madeline and Zhang, Jing and Que, Christian and Simavli, Huseyin and McClurkin, Michael and Guo, Rong and Tobias Elze and de Boer, Johannes F and Chen, Teresa C}
}
@article {1364590,
	title = {Emerging gene therapies for retinal degenerations},
	journal = {J Neurosci},
	volume = {32},
	number = {19},
	year = {2012},
	month = {2012 May 09},
	pages = {6415-20},
	keywords = {Animals, Antioxidants, Genetic Therapy, Humans, Intercellular Signaling Peptides and Proteins, Photoreceptor Cells, Vertebrate, Retinal Degeneration},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.0295-12.2012},
	author = {Cepko, Constance L}
}
@article {314111,
	title = {Intrinsically different retinal progenitor cells produce specific types of progeny},
	journal = {Nat Rev Neurosci},
	volume = {15},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {615-27},
	abstract = {Lineage studies conducted in the retina more than 25 years ago demonstrated the multipotency of retinal progenitor cells (RPCs). The number and types of cells produced by individual RPCs, even from a single time point in development, were found to be highly variable. This raised the question of whether this variability was due to intrinsic differences among RPCs or to extrinsic and/or stochastic effects on equivalent RPCs or their progeny. Newer lineage studies that have made use of molecular markers of RPCs, retrovirus-mediated lineage analyses of specific RPCs and live imaging have begun to provide answers to this question. RPCs that produce two postmitotic daughter cells - that is, terminally dividing RPCs - have been the most well characterized RPCs to date, and have been shown to produce specific types of daughter cells. In addition, recent studies have begun to shed light on the mechanisms that drive the temporal order in which retinal cells are born.},
	keywords = {Animals, Cell Differentiation, Cell Lineage, Models, Biological, Retina, Stem Cells, Visual Pathways},
	issn = {1471-0048},
	doi = {10.1038/nrn3767},
	author = {Cepko, Connie}
}
@article {469026,
	title = {Cell metabolism: Sugar for sight.},
	journal = {Nature},
	volume = {522},
	number = {7557},
	year = {2015},
	month = {2015 Jun 25},
	pages = {428-9},
	issn = {1476-4687},
	doi = {10.1038/522428a},
	author = {Cepko, Connie and Punzo, Claudio}
}
@article {1363252,
	title = {Retinal gene therapy coming of age},
	journal = {Hum Gene Ther},
	volume = {24},
	number = {3},
	year = {2013},
	month = {2013 Mar},
	pages = {242-4},
	issn = {1557-7422},
	doi = {10.1089/hum.2013.050},
	author = {Cepko, Connie L and Vandenberghe, Luk H}
}
@article {1651344,
	title = {Influence of Starch on the Structure-Properties Relationship in Polyethylene Glycol/Polycaprolactone Diol Polyurethanes},
	journal = {Polymers (Basel)},
	year = {2022},
	author = {Cespedes, JF and Ar{\'e}valo-Alquichire, S and Diaz, LE and Valero, MF}
}
@article {1655708,
	title = {Assessment of the Anti-Thrombogenic Activity of Polyurethane Starch Composites},
	journal = {J Funct Biomater},
	volume = {13},
	number = {4},
	year = {2022},
	month = {2022 Oct 12},
	abstract = {The increasing morbidity and mortality of patients due to post-surgery complications of coronary artery bypass grafts (CABPG) are related to blood-material interactions. Thus, the characterization of the thrombogenicity of the biomaterial for cardiovascular devices is of particular interest. This research evaluated the anti-thrombogenic activity of polyurethanes-starch composites. We previously synthesized polyurethane matrices that were obtained from polycaprolactone diol (PCL), polyethylene glycol (PEG), pentaerythritol (PE), and isophorone diisocyanate (IPDI). In addition, potato starch (AL-N) and zwitterionic starch (AL-Z) were added as fillers. The anti-thrombogenic property was characterized by the clot formation time, platelet adhesion, protein absorption, TAT complex levels, and hemolysis. Additionally, we evaluated the cell viability of the endothelial and smooth muscle cells. Statically significant differences among the polyurethane matrices (P1, P2, and P3) were found for protein absorption and the blood clotting time without fillers. The polyurethanes composites with AL-Z presented an improvement in the anti-thrombogenic property. On the other hand, the composites with AL-Z reduced the viability of the endothelial cells and did not significantly affect the AoSCM (except for P1, which increased). These results classify these biomaterials as inert; therefore, they can be used for cardiovascular applications.},
	issn = {2079-4983},
	doi = {10.3390/jfb13040184},
	author = {Cespedes, Jhoan F and Ar{\'e}valo-Alquichire, Said and Diaz, Luis E and Valero, Manuel F}
}
@article {397776,
	title = {Early Diagnosis of Subclinical Interferon Alpha-Associated Optic Neuropathy Using Fluorescein Angiography.},
	journal = {J Neuroophthalmol},
	volume = {35},
	number = {3},
	year = {2015},
	month = {2015 Sep},
	pages = {280-3},
	abstract = {We report a case of a 57-year-old man who presented with decreased visual acuity in the left eye secondary to nonarteritic anterior ischemic optic neuropathy (NAION) while on therapy with interferon-α for hepatitis C. Fundus fluorescein angiography revealed late leakage of both optic discs, consistent with bilateral disease. One week later, the patient developed clinical signs and symptoms consistent with NAION in the fellow eye. Fluorescein angiography may play an important role in identifying subclinical NAION in patients taking interferon-α.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000238},
	author = {Cestari, Dean M and Lessell, Simmons and Mantopoulos, Dimosthenis}
}
@article {753671,
	title = {Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic Optic Neuropathy?},
	journal = {J Neuroophthalmol},
	volume = {36},
	number = {3},
	year = {2016},
	month = {2016 Sep},
	pages = {329-33},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000397},
	author = {Cestari, Dean M and Arnold, Anthony}
}
@article {913416,
	title = {Demographic, Systemic, and Ocular Factors Associated with Nonarteritic Anterior Ischemic Optic Neuropathy.},
	journal = {Ophthalmology},
	volume = {123},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {2446-2455},
	abstract = {OBJECTIVE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a devastating ocular condition causing permanent vision loss. Little is known about risk factors for developing this disease. We assessed demographic, systemic, and ocular factors associated with NAION. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Beneficiaries between 40 and 75 years old without NAION at baseline enrolled in a large U.S. managed care network. METHODS: Enrollees were monitored continuously for >=2 years between 2001 and 2014 to identify those newly diagnosed with NAION (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 377.41). All persons were under ophthalmic surveillance and all cases had >=1 confirmatory ICD-9-CM code for NAION during follow-up. MAIN OUTCOME MEASURES: Multivariable Cox regression modeling was used to generate hazard ratios (HRs) with 95\% confidence intervals (CIs) to describe the statistical relationship between selected demographic characteristics, systemic and ocular conditions, and the hazard of developing NAION. RESULTS: Of 1 381 477 eligible enrollees, 977 (0.1\%) developed NAION during a mean {\textpm} standard deviation (SD) follow-up of 7.8{\textpm}3.1 years. The mean {\textpm} SD age for NAION cases at the index date was 64.0{\textpm}9.2 years vs. 58.4{\textpm}9.4 years for the remainder of the beneficiaries. After adjustment for confounding factors, each additional year older was associated with a 2\% increased hazard of NAION (HR\&nbsp;= 1.02; 95\% CI: 1.01-1.03). Female subjects had a 36\% decreased hazard of developing NAION (HR\&nbsp;= 0.64; 95\% CI: 0.55-0.74) compared with male subjects. Compared with whites, Latinos had a 46\% decreased hazard of developing NAION (HR\&nbsp;= 0.54; 95\% CI: 0.36-0.82), whereas African ancestry was not significantly associated with NAION (HR\&nbsp;= 0.91; 95\% CI: 0.72-1.15). Systemic diseases associated with NAION included hypertension (HR\&nbsp;= 1.62; 95\% CI: 1.26-2.07) and hypercoagulable states (HR\&nbsp;= 2.46; 95\% CI: 1.51-4.00). Although diabetes mellitus (DM) was not significantly associated with NAION compared with those without DM (P\&nbsp;= 0.45), patients with end-organ involvement from DM had a 27\% increased hazard of NAION relative to those with uncomplicated DM (HR\&nbsp;= 1.27; 95\% CI: 1.01-1.59). Ocular diseases associated with NAION were age-related macular degeneration (HR\&nbsp;= 1.29; 95\% CI: 1.08-1.54) and retinal vein occlusion (HR\&nbsp;= 3.94; 95\% CI: 3.11-4.99). CONCLUSIONS: Our study identified several modifiable risk factors that may be associated with NAION. Should future studies confirm these findings, they may offer opportunities to prevent or treat this debilitating condition.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.08.017},
	author = {Cestari, Dean M and Gaier, Eric D and Bouzika, Peggy and Blachley, Taylor S and De Lott, Lindsey B and Rizzo, Joseph F and Wiggs, Janey L and Kang, Jae H and Pasquale, Louis R and Stein, Joshua D}
}
@article {1295855,
	title = {Case 2-2018. A 41-Year-Old Woman with Vision Disturbances and Headache},
	journal = {N Engl J Med},
	volume = {378},
	number = {3},
	year = {2018},
	month = {2018 01 18},
	pages = {282-289},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc1701763},
	author = {Cestari, Dean M and Cunnane, Mary E and Rizzo, Joseph F and Stone, John H}
}
@article {1323920,
	title = {Vertical rectus muscle recession versus combined vertical and horizontal rectus muscle recession in patients with thyroid eye disease and hypotropia},
	journal = {J AAPOS},
	year = {2018},
	month = {2018 Jul 19},
	abstract = {PURPOSE: To compare the postoperative vertical drift in patients with thyroid eye disease (TED) with hypotropia who underwent vertical rectus recession alone versus recession combined with horizontal rectus recession. METHODS: The medical records of patients with TED who underwent strabismus surgery for hypotropia between 2006 and 2015 were reviewed retrospectively. Patients were divided into two groups: group 1 underwent vertical rectus recession only; group 2 underwent vertical rectus recession plus horizontal rectus recession. Data collection included pre- and postoperative deviation measurements and amount of surgical recession performed. The amount of postoperative vertical drift between groups was compared. RESULTS: Of 67 patients who underwent surgery during the study period, 18 met inclusion criteria, 9 in each group. Mean postoperative hypotropia was 24.2 in group 1 and 24.5 in group 2 (P = 0.82). Mean vertical deviations were 0.3 and -2.2 (P = 0.134) on postoperative day 1 -0.9 and -8.0 (P = 0.043) at final follow-up for groups 1 and 2. Mean postoperative vertical drift toward hypertropia was 1.2 in group 1 and 6.8 in group 2 (P = 0.048). The surgical success rate for group 1 was superior to that for group 2 (89\% vs 67\% [P = 0.024]). CONCLUSIONS: There was a significantly larger postoperative vertical drift in TED patients with hypotropia who had combined vertical rectus and horizontal rectus recessions compared with those who underwent vertical rectus recession alone.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2018.04.007},
	author = {Cestari, Dean M and Freire, Marcelle V and Chun, Bo Young}
}
@article {1661835,
	title = {Polypoidal Choroidal Vasculopathy Based on Non-ICGA Criteria in White Patients With Neovascular Age-Related Macular Degeneration},
	journal = {Am J Ophthalmol},
	volume = {244},
	year = {2022},
	month = {2022 Dec},
	pages = {58-67},
	abstract = {PURPOSE: To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study. METHODS: A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA). De-identified images of study eyes were sent to 2 groups of graders. Group 1 reviewed CFP, OCT, and FFA to confirm nAMD diagnosis. Group 2 reviewed CFP and OCT to determine highly suggestive features for PCV. Probable PCV diagnosis defined as the presence of >=2 of 4 highly suggestive features for PCV: notched or fibrovascular pigment epithelial detachment (PED) on CFP, sharply-peaked PED, notched PED, and hyperreflective ring on OCT. RESULTS: Eleven eyes were excluded because of poor image quality (6) or non-nAMD diagnosis (5). Of 197 eligible eyes (197 patients), the mean age (SD) was 78.8 years (8.9), 44.2\% were men, 26.4\% were Hispanic, and 73.6\% were non-Hispanic White individuals; 41.1\%, 23.4\%, 9.1\%, and 2.5\% had >=1, >=2, >=3, and 4 highly suggestive features. Results showed that 23.4\% (95\% CI, 17.6\%-29.9\%) had probable PCV diagnosis. Predominantly occult CNV was more frequently found in probable PCV than nAMD subgroup (84.8\% vs 64.9\%, P\&nbsp;=\&nbsp;.01). Hispanic White individuals had a lower prevalence of probable PCV than non-Hispanic White individuals (9.6\% vs 28.2\%, P\&nbsp;=\&nbsp;.006) CONCLUSIONS: These findings suggest that probable PCV occurs between 17.6\% and 29.9\% in White individuals with nAMD, and more commonly in non-Hispanic than in Hispanic White individuals.},
	keywords = {Aged, Choroid, Choroidal Neovascularization, Cross-Sectional Studies, Female, Fluorescein Angiography, Humans, Macular Degeneration, Male, Polyps, Retinal Detachment, Retrospective Studies, Tomography, Optical Coherence, White People},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.07.024},
	author = {Chaikitmongkol, Voraporn and Ozimek, Malgorzata and Srisomboon, Titipol and Patikulsila, Direk and Fraser-Bell, Samantha and Chhablani, Jay and Choovuthayakorn, Janejit and Watanachai, Nawat and Kunavisarut, Paradee and Rodr{\'\i}guez-Vald{\'e}s, Patricio J and Lozano-Rechy, David and Lupidi, Marco and Al-Sheikh, Mayss and Fung, Adrian T and Busch, Catharina and Mehta, Hemal and Gabrielle, Pierre-Henry and Zur, Dinah and Ramon, Dan and Sangkaew, Apisara and Ingviya, Thammasin and Amphornprut, Atchara and Cebeci, Zafer and Couturier, Aude and Mendes, Thais Sousa and Giancipoli, Ermete and Iglicki, Matias and Invernizzi, Alessandro and Lains, Ines and Rehak, Matus and Sala-Puigdollers, Anna and Okada, Mali and Loewenstein, Anat and Bressler, Neil M}
}
@article {1347431,
	title = {Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sj{\"o}gren Syndrome},
	journal = {Int J Mol Sci},
	volume = {19},
	number = {10},
	year = {2018},
	month = {2018 Oct 20},
	abstract = {Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sj{\"o}gren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines (, ) and other potentially disease-relevant genes (, ) were upregulated in male lacrimal glands. Expression of and , in particular, remained significantly upregulated in the lacrimal glands of lymphocyte-deficient NOD-severe combined immunodeficiency (SCID) mice and their expression was modulated by type I interferon signaling. Notably, -deficient NOD mice did not develop dacryoadenitis. Together these data identify disease-relevant genes upregulated in the context of male-specific dacryoadenitis and demonstrate a requisite role for type I interferon signaling in lacrimal gland autoimmunity in NOD mice.},
	issn = {1422-0067},
	doi = {10.3390/ijms19103259},
	author = {Chaly, Yury and Barr, Jennifer Y and Sullivan, David A and Thomas, Helen E and Brodnicki, Thomas C and Lieberman, Scott M}
}
@article {591266,
	title = {Detection of Strabismus by Non-Health Care Professionals in an Ethnically Diverse Set of Images.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {1},
	year = {2016},
	month = {2016 Jan 1},
	pages = {30-6},
	abstract = {IMPORTANCE: Understanding the criteria for when strabismus becomes detectable by non-health care professionals could influence the goals for determining the success of surgical intervention and how patients with such misalignments are counseled. OBJECTIVE: To examine the magnitude at which strabismus is detectable by lay observers in an ethnically diverse set of images. DESIGN, SETTING, AND PARTICIPANTS: Photographs of 12 ethnically diverse models (black, white, and Asian) were simulated to have strabismus from esotropia of 21 prism diopters (∆) to exotropia of 21∆. From July 1, 2007, to October, 1, 2008, images were presented to 120 non-health care professionals aged 21 years or older from the general community in Boston, Massachusetts, who were asked whether strabismus was present. Analysis was conducted from November 1, 2008, to March 31, 2009. MAIN OUTCOMES AND MEASURES: The threshold angle for detecting strabismus to enable 70\% of lay observers to make a positive determination whether strabismus is present. RESULTS: In white and black models, the threshold allowing a 70\% positive detection rate was higher for esotropia than for exotropia (P \&lt; .001 for both). For white models, the threshold was 23.2∆ (95\% CI, 21.0∆ to 26.5∆) for esotropia and 13.5∆ (95\% CI, 12.5∆ to 14.6∆) for exotropia. For black models, the threshold was 20.8∆ (95\% CI, 19.2∆ to 22.2∆) for esotropia and 16.3∆ (95\% CI, 15.5∆ to 17.2∆) for exotropia. Asian models showed an opposite trend, with the threshold allowing a 70\% positive detection rate for esotropia (14.3∆; 95\% CI, 13.2∆ to 15.7∆) being lower than that for exotropia (20.9∆; 95\% CI, 18.0∆ to 24.6∆) (P \&lt; .001). CONCLUSIONS AND RELEVANCE: Esotropia was easier for lay observers to detect than exotropia in Asian models, and exotropia was easier to detect than esotropia in white and black models. This information should be considered when managing patients who have concerns about the social significance of their strabismus. Future studies should include diverse individuals and make an effort to account for individual factors that may alter the perception of strabismus.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.4082},
	author = {Chan, Kimberley W and Deng, Li and Weissberg, Erik M}
}
@article {1593837,
	title = {Pneumatic Vitreolysis with Perfluoropropane for Vitreomacular Traction with and without Macular Hole: DRCR Retina Network Protocols AG and AH},
	journal = {Ophthalmology},
	volume = {128},
	number = {11},
	year = {2021},
	month = {2021 11},
	pages = {1592-1603},
	abstract = {PURPOSE: To evaluate pneumatic vitreolysis (PVL) in eyes with vitreomacular traction (VMT) with and without full-thickness macular hole (FTMH). DESIGN: Two multicenter (28 sites) studies: a randomized clinical trial comparing PVL with observation (sham injection) for VMT without FTMH (Protocol AG) and a single-arm study assessing PVL for FTMH (Protocol AH). PARTICIPANTS: Participants were adults with central VMT (vitreomacular adhesion was <=3000 μm). In Protocol AG, visual acuity (VA) was 20/32 to 20/400. In Protocol AH, eyes had a FTMH (<=250 μm at the narrowest point) and VA of 20/25 to 20/400. METHODS: Pneumatic vitreolysis using perfluoropropane (C3F8) gas. MAIN OUTCOME MEASURES: Central VMT release at 24 weeks (Protocol AG) and FTMH closure at 8 weeks (Protocol AH). RESULTS: From October 2018 through February 2020, 46 participants were enrolled in Protocol AG, and 35 were enrolled in Protocol AH. Higher than expected rates of retinal detachment and tear resulted in early termination of both protocols. Combining studies, 7 of 59 eyes (12\% [95\% CI, 6\%-23\%]; 2 eyes in Protocol AG, 5 eyes in Protocol AH) that received PVL developed rhegmatogenous retinal detachment (n\&nbsp;= 6) or retinal tear (n\&nbsp;= 1). At 24 weeks in Protocol AG, 18 of 23 eyes in the PVL group (78\%) versus 2 of 22 eyes in the sham group (9\%) achieved central VMT release without rescue vitrectomy (adjusted risk difference, 66\% [95\% CI, 44\%-88\%]; P\&lt; 0.001). The mean change in VA from baseline at 24 weeks was 6.7 letters in the PVL group and 6.1 letters in the sham group (adjusted difference, -0.8 [95\% CI, -6.1 to 4.5]; P\&nbsp;= 0.77). In Protocol AH, 10 of 35 eyes (29\% [95\% CI, 16\%-45\%]) achieved FTMH closure without rescue vitrectomy at 8 weeks. The mean change in VA from baseline at 8 weeks was -1.5 letters (95\% CI, -10.3 to 7.3 letters). CONCLUSIONS: In most eyes with VMT, PVL induced hyaloid release. In eyes with FTMH, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears.},
	keywords = {Aged, Contrast Media, Female, Fluorocarbons, Follow-Up Studies, Humans, Intravitreal Injections, Male, Retinal Perforations, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity, Vitrectomy, Vitreous Body, Vitreous Detachment},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.05.005},
	author = {Chan, Clement K and Mein, Calvin E and Glassman, Adam R and Beaulieu, Wesley T and Calhoun, Claire T and Jaffe, Glenn J and Jampol, Lee M and MacCumber, Mathew W and Maguire, Maureen G and Maturi, Raj K and Salehi-Had, Hani and Rofagha, Soraya and Sun, Jennifer K and Martin, Daniel F and DRCR Retina Network}
}
@article {1351143,
	title = {Evaluating choroidal thickness in diabetic retinopathy},
	journal = {Clin Ophthalmol},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {1185-6},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S66193},
	author = {Chan, Chee Yee and Papakostas, Thanos D and Vavvas, Demetrios G}
}
@article {1424797,
	title = {The Genetic Influence on Corticosteroid-Induced Ocular Hypertension: A Field Positioned for Discovery},
	journal = {Am J Ophthalmol},
	volume = {202},
	year = {2019},
	month = {2019 Jun},
	pages = {1-5},
	abstract = {PURPOSE: To provide evidence that corticosteroid-induced ocular hypertension has a genetic component. DESIGN: Evidence-based perspective. METHODS: We conducted a comprehensive literature search for studies exploring genetic influences on intraocular pressure responses to corticosteroid treatment. RESULTS: Studies demonstrating increased risk of corticosteroid-induced ocular hypertension among first-degree relatives of affected individuals support a genetic contribution to the disease. Family and personal history of primary open-angle glaucoma also increases the risk of corticosteroid-induced intraocular pressure elevation, suggesting common genetic etiologies. A number of studies have attempted to identify predisposing genetic factors; however, reproducible findings have not yet been reported. The recent availability of large data sets with clinical and genetic data for patients affected by corticosteroid-induced ocular hypertension and glaucoma provides new opportunities to study the genetic underpinnings of this important condition. CONCLUSIONS: There is substantial evidence suggesting a genetic component to corticosteroid-related ocular hypertension and glaucoma, but specific genetic risk factors have yet to be identified. The current confluence of large genetic data sets and affordable genetic sequencing technologies has great potential for discovering the genes that increase risk for this blinding complication of corticosteroid therapy.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.02.001},
	author = {Chan, Weilin and Wiggs, Janey L and Sobrin, Lucia}
}
@article {314116,
	title = {Evaluation of choroidal thickness among patients with oculocutaneous albinism},
	journal = {Br J Ophthalmol},
	volume = {98},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {1135},
	keywords = {Albinism, Oculocutaneous, Choroid, Female, Humans, Male, Refractive Errors},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-305395},
	author = {Chan, Chee Yee and Papakostas, Thanos D and Vavvas, Demetrios}
}
@article {1522720,
	title = {Cell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors and -regulatory modules in the retina},
	journal = {Development},
	volume = {147},
	number = {14},
	year = {2020},
	month = {2020 Jul 26},
	abstract = {Transcription factors (TFs) are often used repeatedly during development and homeostasis to control distinct processes in the same and/or different cellular contexts. Considering the limited number of TFs in the genome and the tremendous number of events that need to be regulated, re-use of TFs is necessary. We analyzed how the expression of the homeobox TF, orthodenticle homeobox\&nbsp;2 (Otx2), is regulated in a cell type- and stage-specific manner during development in the mouse retina. We identified seven -regulatory modules (CRMs), among which the O5, O7 and O9 CRMs mark three distinct cellular contexts of Otx2 expression. We discovered that Otx2, Crx and Sox2, which are well-known TFs regulating retinal development, bind to and activate the O5, O7 or O9 CRMs, respectively. The chromatin status of these three CRMs was found to be distinct in different retinal cell types and at different stages. We conclude that retinal cells use a cohort of TFs with different expression patterns and multiple CRMs with different chromatin configurations to regulate the expression of Otx2 precisely.},
	issn = {1477-9129},
	doi = {10.1242/dev.187922},
	author = {Chan, Candace S Y and Lonfat, Nicolas and Zhao, Rong and Davis, Alexander E and Li, Liang and Wu, Man-Ru and Lin, Cheng-Hui and Ji, Zhe and Cepko, Constance L and Wang, Sui}
}
@article {1580500,
	title = {Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses},
	journal = {Sci Transl Med},
	volume = {13},
	number = {580},
	year = {2021},
	month = {2021 Feb 10},
	abstract = {Nucleic acids are used in many therapeutic modalities, including gene therapy, but their ability to trigger host immune responses in vivo can lead to decreased safety and efficacy. In the case of adeno-associated viral (AAV) vectors, studies have shown that the genome of the vector activates Toll-like receptor 9 (TLR9), a pattern recognition receptor that senses foreign DNA. Here, we engineered AAV vectors to be intrinsically less immunogenic by incorporating short DNA oligonucleotides that antagonize TLR9 activation directly into the vector genome. The engineered vectors elicited markedly reduced innate immune and T cell responses and enhanced gene expression in clinically relevant mouse and pig models across different tissues, including liver, muscle, and retina. Subretinal administration of higher-dose AAV in pigs resulted in photoreceptor pathology with microglia and T cell infiltration. These adverse findings were avoided in the contralateral eyes of the same animals that were injected with the engineered vectors. However, intravitreal injection of higher-dose AAV in macaques, a more immunogenic route of administration, showed that the engineered vector delayed but did not prevent clinical uveitis, suggesting that other immune factors in addition to TLR9 may contribute to intraocular inflammation in this model. Our results demonstrate that linking specific immunomodulatory noncoding sequences to much longer therapeutic nucleic acids can "cloak" the vector from inducing unwanted immune responses in multiple, but not all, models. This "coupled immunomodulation" strategy may widen the therapeutic window for AAV therapies as well as other DNA-based gene transfer methods.},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.abd3438},
	author = {Chan, Ying Kai and Wang, Sean K and Chu, Colin J and Copland, David A and Letizia, Alexander J and Costa Verdera, Helena and Chiang, Jessica J and Sethi, Meher and Wang, May K and Neidermyer, William J and Chan, Yingleong and Lim, Elaine T and Graveline, Amanda R and Sanchez, Melinda and Boyd, Ryan F and Vihtelic, Thomas S and Inciong, Rolando Gian Carlo O and Slain, Jared M and Alphonse, Priscilla J and Xue, Yunlu and Robinson-McCarthy, Lindsey R and Tam, Jenny M and Jabbar, Maha H and Sahu, Bhubanananda and Adeniran, Janelle F and Muhuri, Manish and Tai, Phillip W L and Xie, Jun and Krause, Tyler B and Vernet, Andyna and Pezone, Matthew and Xiao, Ru and Liu, Tina and Wang, Wei and Kaplan, Henry J and Gao, Guangping and Dick, Andrew D and Mingozzi, Federico and McCall, Maureen A and Cepko, Constance L and Church, George M}
}
@article {1615207,
	title = {Glaucoma Drainage Devices Calculator App: A Modern Clinical Decision Tool},
	journal = {Ophthalmol Glaucoma},
	volume = {4},
	number = {5},
	year = {2021},
	month = {2021 Sep-Oct},
	pages = {550-551},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.01.002},
	author = {Chandramouli, Shivram A and Glaser, Tanya S and Umunakwe, Obinna and Gupta, Divakar and Margeta, Milica A and Challa, Pratap and Kuo, Anthony N and Freedman, Sharon F}
}
@article {1511484,
	title = {Imaging Methods for Differentiating Pediatric Papilledema from Pseudopapilledema: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {127},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {1416-1423},
	abstract = {PURPOSE: To review the published literature on the accuracy of ophthalmic imaging methods to differentiate between papilledema and pseudopapilledema in children. METHODS: Literature searches were conducted in January 2020 in the PubMed database for English-language studies with no date restrictions and in the Cochrane Library database without any restrictions. The combined searches yielded 354 abstracts, of which 17 were reviewed in full text. Six of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. All 6 included studies were rated as level III evidence. RESULTS: Fluorescein angiography, a combination of 2 OCT protocols, and multicolor confocal scanning laser ophthalmoscopy (Spectralis SD-OCT; Heidelberg Engineering, Heidelberg, Germany) demonstrated the highest positive percent agreement (92\%-100\%; 95\% confidence interval [CI], 69\%-100\%) and negative percent agreement (92\%-100\%; 95\% CI, 70\%-100\%) with a clinical diagnosis of papilledema in children. However, results must be interpreted with caution owing to methodologic limitations, including a small sample size leading to wide CIs and an overall lack of data (there was only 1 study each for the above methods and protocols). Ultrasonographic measures showed either a high positive percent agreement (up to 95\%) with low negative percent agreement (as low as 58\%) or vice versa. Autofluorescence and fundus photography showed a lower positive (40\%-60\%) and negative (57\%) percent agreement. CONCLUSIONS: Although several imaging methods demonstrated high positive and negative percent agreement with clinical diagnosis, no ophthalmic imaging method conclusively differentiated papilledema from pseudopapilledema in children because of the lack of high-quality evidence. Clinicians must continue to conduct thorough history-taking and examination and make judicious use of ancillary testing to determine which children warrant further workup for papilledema.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.03.027},
	author = {Chang, Melinda Y and Binenbaum, Gil and Heidary, Gena and Morrison, David G and Galvin, Jennifer A and Trivedi, Rupal H and Pineles, Stacy L}
}
@article {1498251,
	title = {SJS/TEN 2019: From science to translation},
	journal = {J Dermatol Sci},
	year = {2020},
	month = {2020 Mar 07},
	abstract = {Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.},
	issn = {1873-569X},
	doi = {10.1016/j.jdermsci.2020.02.003},
	author = {Chang, Wan-Chun and Abe, Riichiro and Anderson, Paul and Anderson, Wanpen and Ardern-Jones, Michael R and Beachkofsky, Thomas M and Bell{\'o}n, Teresa and Biala, Agnieszka K and Bouchard, Charles and Cavalleri, Gianpiero L and Chapman, Nicole and Chodosh, James and Choi, Hyon K and Cibotti, Ricardo R and Divito, Sherrie J and Dewar, Karen and Dehaeck, Ulrike and Etminan, Mahyar and Forbes, Diane and Fuchs, Esther and Goldman, Jennifer L and Holmes, James H and Hope, Elyse A and Hung, Shuen-Iu and Hsieh, Chia-Ling and Iovieno, Alfonso and Jagdeo, Julienne and Kim, Mee Kum and Koelle, David M and Lacouture, Mario E and Le Pallec, Sophie and Lehloenya, Rannakoe J and Lim, Robyn and Lowe, Angie and McCawley, Jean and McCawley, Julie and Micheletti, Robert G and Mockenhaupt, Maja and Niemeyer, Katie and Norcross, Michael A and Oboh, Douglas and Olteanu, Cristina and Pasieka, Helena B and Peter, Jonathan and Pirmohamed, Munir and Rieder, Michael and Saeed, Hajirah N and Shear, Neil H and Shieh, Christine and Straus, Sabine and Sukasem, Chonlaphat and Sung, Cynthia and Trubiano, Jason A and Tsou, Sheng-Ying and Ueta, Mayumi and Volpi, Simona and Wan, Chen and Wang, Hongsheng and Wang, Zhao-Qing and Weintraub, Jessica and Whale, Cindy and Wheatley, Lisa M and Whyte-Croasdaile, Sonia and Williams, Kristina B and Wright, Galen and Yeung, Sonia N and Zhou, Li and Chung, Wen-Hung and Phillips, Elizabeth J and Carleton, Bruce C}
}
@article {1580481,
	title = {Combined pars plana glaucoma drainage device placement and vitrectomy using a vitrectomy sclerotomy site for tube placement: a case series},
	journal = {BMC Ophthalmol},
	volume = {21},
	number = {1},
	year = {2021},
	month = {2021 Feb 25},
	pages = {106},
	abstract = {PURPOSE: The purpose of this study is to report the safety and efficacy of pars plana glaucoma drainage devices with pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement in patients with refractory glaucoma. METHODS: Retrospective case series of 28 eyes of 28 patients who underwent combined pars plana glaucoma drainage device and pars plana vitrectomy between November 2016 and September 2019 at Massachusetts Eye and Ear. Main outcome measures were intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity, and complications. Statistical tests were performed with R and included Kaplan-Meier analyses, Wilcoxon paired signed-rank tests, and Fisher tests. RESULTS: Mean IOP decreased from 22.8 mmHg to 11.8 mmHg at 1.5 years (p = 0.002), and mean medication burden decreased from 4.3 to 2.1 at 1.5 years (p = 0.004). Both IOP and medication burden were significantly lower at all follow-up time points. The probability of achieving 5 \&lt; IOP <= 18 mmHg with at least 20\% IOP reduction from preoperative levels was 86.4\% at 1 year and 59.8\% at 1.5 years. At their last visit, three eyes (10.7\%) achieved complete success with IOP reduction as above without medications, and 14 eyes (50.0\%) achieved qualified success with medications. Hypotony was observed in 1 eye (3.6\%) prior to 3 months postoperatively and 0 eyes after 3 months. Visual acuity was unchanged or improved in 23 eyes (82.1\%) at their last follow-up. Two patients had a visual acuity decrease of \&gt; 2 lines. Two eyes required subsequent pars plana vitrectomies for tube obstruction, and one eye had transient hypotony. CONCLUSIONS: The results of pars plana glaucoma drainage device and pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement are promising, resulting in significant IOP and medication-burden reductions through postoperative year 1.5 without additional risk of postoperative complications. Inserting glaucoma drainage devices into an existing vitrectomy sclerotomy site may potentially save surgical time by obviating the need to create another sclerotomy for tube placement and suture one of the vitrectomy ports.},
	issn = {1471-2415},
	doi = {10.1186/s12886-021-01872-z},
	author = {Chang, Enchi Kristina and Gupta, Sanchay and Chachanidze, Marika and Miller, John B and Chang, Ta Chen and Sol{\'a}-Del Valle, David A}
}
@article {1623373,
	title = {Corrigendum to {\textquoteright}SJS/TEN 2019: From science to translation{\textquoteright} [J. Dermatol. Sci. 98/1 (2020) 2-12]},
	journal = {J Dermatol Sci},
	volume = {104},
	number = {2},
	year = {2021},
	month = {2021 Nov},
	pages = {146-147},
	issn = {1873-569X},
	doi = {10.1016/j.jdermsci.2021.09.008},
	author = {Chang, Wan-Chun and Abe, Riichiro and Anderson, Paul and Anderson, Wanpen and Ardern-Jones, Michael R and Beachkofsky, Thomas M and Bell{\'o}n, Teresa and Biala, Agnieszka K and Bouchard, Charles and Cavalleri, Gianpiero L and Chapman, Nicole and Chodosh, James and Choi, Hyon K and Cibotti, Ricardo R and Divito, Sherrie J and Dewar, Karen and Dehaeck, Ulrike and Etminan, Mahyar and Forbes, Diane and Fuchs, Esther and Goldman, Jennifer L and Holmes, James H and Hope, Elyse A and Hung, Shuen-Iu and Hsieh, Chia-Ling and Iovieno, Alfonso and Jagdeo, Julienne and Kim, Mee Kum and Koelle, David M and Lacouture, Mario E and Le Pallec, Sophie and Lehloenya, Rannakoe J and Lim, Robyn and Lowe, Angie and McCawley, Jean and McCawley, Julie and Micheletti, Robert G and Mockenhaupt, Maja and Niemeyer, Katie and Norcross, Michael A and Oboh, Douglas and Olteanu, Cristina and Pasieka, Helena B and Peter, Jonathan and Pirmohamed, Munir and Rieder, Michael and Saeed, Hajirah N and Shear, Neil H and Shieh, Christine and Straus, Sabine and Sukasem, Chonlaphat and Sung, Cynthia and Trubiano, Jason A and Tsou, Sheng-Ying and Ueta, Mayumi and Volpi, Simona and Wan, Chen and Wang, Hongsheng and Wang, Zhao-Qing and Weintraub, Jessica and Whale, Cindy and Wheatley, Lisa M and Whyte-Croasdaile, Sonia and Williams, Kristina B and Wright, Galen and Yeung, Sonia N and Zhou, Li and Chung, Wen-Hung and Phillips, Elizabeth J and Carleton, Bruce C}
}
@article {1589758,
	title = {Safety and efficacy of microinvasive glaucoma surgery with cataract extraction in patients with normal-tension glaucoma},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Apr 26},
	pages = {8910},
	abstract = {This study assesses the safety and efficacy of microinvasive glaucoma surgery (MIGS) with cataract extraction in patients with normal-tension glaucoma (NTG). In our sample of 45 NTG patients, mean intraocular pressure (IOP) decreased from 13.7 to 12.3\&nbsp;mmHg at 2.5\&nbsp;years, and mean medication burden decreased from 2.0 to 1.1 at 1.5\&nbsp;years. For success defined as IOP reduction >= 30\% from baseline IOP with medication burden reduction from preoperative levels, success probability was 5.4\% at 1.5\&nbsp;years. For success defined as medication burden reduction with an IOP reaching goal IOP as determined by the glaucoma specialist, success probabilities were 67.2\% at 1.5\&nbsp;years and 29.4\% at 2.5\&nbsp;years. At the last follow-up visit, eyes with two MIGS procedures with different mechanisms of action achieved successful medication reduction 68.8\% of the time versus 35.7\% achieved by a single MIGS procedure (p = 0.052). At their last visit, visual acuity was unchanged or improved in all eyes (100\%). MIGS with cataract surgery results in modest reductions in IOP and medication burden in NTG patients, which may lead to lower costs and better therapeutic compliance. A combination of two MIGS procedures with different mechanisms of action may potentially be more effective in reducing medication burden than a single MIGS procedure in NTG patients. Further research is necessary to ascertain whether MIGS for NTG patients may help decrease medication burden while helping achieve goal IOP.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-88358-6},
	author = {Chang, Enchi Kristina and Gupta, Sanchay and Chachanidze, Marika and Hall, Nathan and Chang, Ta Chen and Sol{\'a}-Del Valle, David}
}
@article {1642016,
	title = {Cataract progression after Nd:YAG laser iridotomy in primary angle-closure suspect eyes},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {9},
	year = {2023},
	month = {2023 Sep},
	pages = {1264-1268},
	abstract = {BACKGROUND/AIMS: Prophylactic laser peripheral iridotomy (LPI) is performed in primary angle-closure suspect (PACS) eyes to prevent acute angle-closure attacks. However, accelerated cataractogenesis is a potential risk of the procedure that may result in decreased visual acuity. We aimed to assess the long-term impact of LPI on cataract formation in Chinese PACS. METHODS: In the Zhongshan Angle Closure Prevention Trial, eligible bilateral PACS participants received LPI in one randomly selected eye, while the fellow eye remained untreated. Cataract was graded using the Lens Opacity Classification System III, and progression was defined as an increase in grade by at least two units in any category or cataract surgery. RESULTS: In total, 889 participants were randomly assigned to LPI in one eye only (mean age 59{\textpm}5 years, 83\% female). At 72 months, treated eyes had slightly higher average nuclear grades (p\&lt;0.001). However, there were no differences between eyes for predefined cataract progression (cumulative probability at 72 months: 21.2\% in LPI vs 19.4\% in control, p=0.401) or cataract surgery (1\% for both). While LPI-treated eyes had a 10\% higher risk of progression over 6 years (HR=1.10 (95\% CI 0.88 to 1.36)), this was not statistically significant. Visual acuity at 72 months was similar in treated and untreated eyes (p=0.43). CONCLUSION: Although lenses were graded on average as slightly more opaque in laser-treated eyes, prophylactic neodymium:yttrium-aluminum-garnet LPI did not cause significant cataract progression. Our results suggest that LPI treatment of asymptomatic narrow angles does not increase the risk of developing clinically meaningful cataract worsening over time. TRIAL REGISTRATION NUMBER: ISRCTN45213099.},
	keywords = {Cataract, Cataract Extraction, Female, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Iridectomy, Iris, Laser Therapy, Lasers, Solid-State, Male, Middle Aged},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-320929},
	author = {Chang, Dolly Shuo-Teh and Jiang, Yuzhen and Kim, Julia Anne and Huang, Shengsong and Munoz, Beatriz and Aung, Tin and He, Mingguang and Foster, Paul J and Friedman, David}
}
@article {1658671,
	title = {Surgical Treatments to Improve Visual Acuity in Infantile Nystagmus Syndrome: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {130},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {331-344},
	abstract = {PURPOSE: To review the literature on the efficacy of surgical procedures to improve visual acuity (VA) in patients with infantile nystagmus syndrome (INS). METHODS: Literature searches were last conducted in January 2022 in the PubMed database for English-language studies with no date restrictions. The combined searches yielded 354 abstracts, of which 46 were reviewed in full text. Twenty-three of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: One included study was a randomized trial; the remaining 22 were case series. The 23 studies included children and adults with INS and a variable proportion with anomalous head position (AHP), strabismus, and sensory diagnoses. The surgical interventions evaluated included large recessions, tenotomy and reattachment (TAR), myectomy with or without pulley fixation, and anterior extirpation of the 4 horizontal rectus muscles, as well as various procedures to correct an AHP in which VA was reported as a secondary outcome. The data were mixed, with improvements in binocular best-corrected visual acuity (BCVA) ranging from no improvement to 0.3 logarithm of the minimum angle of resolution (logMAR), or 3 lines. (Most studies were in the range of 0.05-0.2 logMAR.) Statistically significant improvement in VA was noted in 12 of 16 studies (75\%) that performed statistical analyses, with no clear advantage of any single procedure. Complications and reoperations were lowest in patients who underwent TAR and highest in those who underwent myectomy or anterior extirpation. CONCLUSIONS: The best available evidence suggests that eye muscle surgery in patients with INS results in a modest improvement in VA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Adult, Child, Eye Movements, Humans, Nystagmus, Pathologic, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Ophthalmology, Posture, Visual Acuity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.10.006},
	author = {Chang, Melinda Y and Binenbaum, Gil and Heidary, Gena and Cavuoto, Kara M and Morrison, David G and Trivedi, Rupal H and Kim, Stephen J and Pineles, Stacy L}
}
@article {1655703,
	title = {LGBTQ+ Identity and Ophthalmologist Burnout},
	journal = {Am J Ophthalmol},
	volume = {246},
	year = {2023},
	month = {2023 Feb},
	pages = {66-85},
	abstract = {PURPOSE: To evaluate lesbian, gay, bisexual, transgender, questioning, and other sexual/gender minority (LGBTQ+) orientation as a burnout risk factor among an international ophthalmologist cohort. METHODS: An anonymous, cross-sectional electronic survey was distributed via an Internet platform to characterize the relationship among demographic factors, including LGBTQ+ orientation, and burnout as measured by the Copenhagen Burnout Inventory (CBI). Univariable data analysis (linear) by sexual orientation was performed and variables with an association with a P value of \&lt;0.15 in univariable analysis were included in the multiple linear regression modeling. RESULTS: A total of 403 ophthalmologists participated in the survey. The majority self-identified as "White" (69.2\%), were from North America (72.0\% United States, 18.6\% Canada) and were evenly distributed between age of 30 and 65 years. Overall, 13.2\% of participants identified as LGBTQ+ and 98.2\% as cisgender. Approximately 12\% had witnessed or experienced LGBTQ+-related workplace discrimination or harassment. The personal and work-related burnout scores and confidence limits of persons identified as LGBTQ+ were higher and nonoverlapping compared with those reported as non-LGBTQ+. Multivariable analysis identified significant risk factors for higher personal and work-related burnout scores: LGBTQ+ (11.8 and 11.1, P\&nbsp;=\&nbsp;.0005 and .0023), female gender (5.36 and 4.83, P\&nbsp;=\&nbsp;.0153 and .0434), older age (19.1 and 19.2, P\&nbsp;=\&nbsp;.0173 and .0273). and caretaker stress (6.42 and 5.97, P\&nbsp;=\&nbsp;.0085 and .0239). CONCLUSIONS: LGBTQ+ orientation is a burnout risk factor among ophthalmologists, and LGBTQ+ workplace discrimination may be a contributing factor. Support from ophthalmology organizations to address LGBTQ+-, gender-, and age-related workplace discrimination may decrease burnout. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.},
	keywords = {Adult, Aged, Burnout, Psychological, Cross-Sectional Studies, Female, Gender identity, Humans, Male, Middle Aged, Ophthalmologists, Sexual Behavior, United States},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.10.002},
	author = {Chang, Ta C and A, Rafael and Candelario, Calderon and Berrocal, Audina M and Brice{\~n}o, C{\'e}sar A and Chen, Jenny and Shoham-Hazon, Nir and Berco, Efraim and Sol{\'a}-Del Valle, David and Vanner, Elizabeth A}
}
@article {1762001,
	title = {Sensitivity, specificity and cutoff identifying optic atrophy by macular ganglion cell layer volume in syndromic craniosynostosis},
	journal = {Ophthalmology},
	year = {2023},
	month = {2023 Sep 22},
	abstract = {PURPOSE: Determine sensitivity, specificity, and cut-off of macular ganglion cell layer (GCL) volume consistent with optic atrophy in children with syndromic craniosynostosis (CS). Investigate whether obstructive sleep apnea (OSA), Chiari malformation, history of elevated intracranial pressure (ICP), CS diagnosis, age, or sex independently alter GCL volume with CS. DESIGN: Retrospective cross-sectional study. SUBJECTS: Patients with syndromic CS evaluated at Boston Children{\textquoteright}s Hospital (2010 - 2022) with reliable macular optical coherence tomography (OCT) scans. METHODS: Latest ophthalmic examination that included OCT macula scans was identified. Age at examination, sex, ethnicity, best-corrected logMAR visual acuity, cycloplegic refraction, and funduscopic optic nerve appearance were recorded in addition to history of primary or recurrent elevated ICP, Chiari malformation and OSA. Spectral domain-OCT software quantified segmentation of macula retinal layers, and was manually checked. MAIN OUTCOME MEASURES: Primary outcome was determining sensitivity, specificity and optimal cutoff of GCL volume consistent with optic atrophy. Secondary outcome was determining possible independent association of previously elevated ICP, OSA, Chiari, CS diagnosis, logMAR acuity, age, or sex with altered GCL volume. RESULTS: Median age at examination was 11.9 years (interquartile range (IQR), 8.5-14.8 years). Fifty-eight of 61 patients had reliable macula scans, 74\% were female, and diagnoses were Apert (n=14); Crouzon (n=17); Muenke (n=6); Pfeiffer (n= 6); and Saethre-Chotzen (n=15). Optimal cutoff identifying optic atrophy was GCL volume \&lt;1.02mm3 with a sensitivity of 83\% and specificity of 77\%. Univariate analysis demonstrated significantly lower macular GCL volume with optic atrophy on fundus exam (P\&lt;0.001), Apert syndrome (P\&lt;0.001), history of elevated ICP (P=0.015), Chiari malformation (P=0.001), OSA (P\&lt;0.001), in males (P=0.027) and with worse logMAR acuity (-0.36, P\&lt;0.001). Multivariable median regression analysis confirmed that only OSA (P=0.005), optic atrophy on fundus exam (P=0.003), and worse logMAR acuity (P=0.042) independently associated with lower GCL volume. CONCLUSIONS: Macular GCL volume \&lt;1.02mm3 predicted optic atrophy in patients with CS with sensitive of 83\% and specificity of 77\%. OSA, a treatable often concomitant disorder, was independently associated with lower GCL volume. Surveillance for optic neuropathy by GCL volume proved effective in a population where cognitive skills can limit acquisition of other key ophthalmic measures.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.09.022},
	author = {Chang, Yoon-Hee and Staffa, Steven J and Yavuz Saricay, Leyla and Zurakowski, David and Gise, Ryan and Dagi, Linda R}
}
@article {1608597,
	title = {Non-invasive electrical stimulation as a potential treatment for retinal degenerative diseases},
	journal = {Neural Regen Res},
	volume = {16},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {1558-1559},
	issn = {1673-5374},
	doi = {10.4103/1673-5374.303015},
	author = {Chang, Karen and Enayati, Sam and Cho, Kin-Sang and Utheim, Tor P and Chen, Dong Feng}
}
@article {1761881,
	title = {A Rapidly Expanding Hemorrhagic BRAF-Mutant Orbital Atypical Glomus Tumor},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {40},
	number = {1},
	year = {2024},
	month = {2024 Jan-Feb 01},
	pages = {e11-e14},
	abstract = {A healthy 32-year-old woman presented with the acute onset of left sided eye pain, upper eyelid fullness, and binocular diplopia during light weightlifting. Examination elevated intraocular pressure, proptosis, upper eyelid ptosis, and motility deficits. CT demonstrated a well-circumscribed, homogeneous-appearing extraconal mass in the superior left orbit. The patient underwent an urgent orbitotomy with the excision of a hemorrhagic mass. Histopathology showed a glomus tumor with atypical features and hemorrhagic infarction, best classified as having uncertain malignant potential. A B-Raf proto-oncogene V600E mutation was detected with immunohistochemistry, which suggests a more aggressive tumor behavior yet presents an opportunity for targeted primary or adjunctive therapy. This is the first reported case of a B-Raf proto-oncogene-mutant atypical glomus tumor arising in the orbit.},
	keywords = {Adult, Exophthalmos, Female, Glomus Tumor, Humans, Orbit, Orbital Neoplasms, Proto-Oncogene Proteins B-raf},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002513},
	author = {Chang, Enchi K and Chiou, Carolina A and Lefebvre, Daniel R and Stagner, Anna M}
}
@article {1598037,
	title = {Home- and Office-Based Vergence and Accommodative Therapies for Treatment of Convergence Insufficiency in Children and Young Adults: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {128},
	number = {12},
	year = {2021},
	month = {2021 12},
	pages = {1756-1765},
	abstract = {PURPOSE: To review home- and office-based vergence and accommodative therapies for treatment of convergence insufficiency (CI) in children and young adults up to 35 years of age. METHODS: Literature searches were conducted through October 2020 in the PubMed database for English-language studies. The combined searches yielded 359 abstracts, of which 37 were reviewed in full text. Twelve of these were considered appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. RESULTS: Of the 12 studies included in this assessment, 8 were graded as level I evidence, 2 were graded as level II evidence, and 2 were graded as level III evidence. Two of the level I studies included older teenagers and young adults; the remainder of the studies exclusively evaluated children. Two randomized controlled trials found that office-based vergence and accommodative therapies were effective in improving motor outcomes in children with symptomatic CI. However, the studies reported conflicting results on the efficacy of office-based therapy for treating symptoms of CI. Data were inconclusive regarding the effectiveness of home-based therapies (including pencil push-ups and home computer therapy) compared with home placebo. In young adults, office-based vergence and accommodative therapies were not superior to placebo in relieving symptoms of CI. CONCLUSIONS: Level I evidence suggests that office-based vergence and accommodative therapies improve motor outcomes in children with symptomatic CI, although data are inconsistent regarding symptomatic relief.\&nbsp;Evidence is insufficient to determine whether home-based therapies are effective.},
	keywords = {Academies and Institutes, Accommodation, Ocular, Adolescent, Adult, Child, Eye Movements, Home Care Services, Humans, Ocular Motility Disorders, Ophthalmology, Orthoptics, Patient Compliance, Patient Satisfaction, Physicians{\textquoteright} Offices, Technology Assessment, Biomedical, United States, Vision, Binocular, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.05.017},
	author = {Chang, Melinda Y and Morrison, David G and Binenbaum, Gil and Heidary, Gena and Trivedi, Rupal H and Galvin, Jennifer A and Pineles, Stacy L}
}
@article {503916,
	title = {Goal-determined metrics to assess outcomes ofexotropia surgery.},
	journal = {J AAPOS},
	year = {2015},
	month = {2015 Jul 30},
	abstract = {PURPOSE: To present a goal-determined methodology for monitoring outcomes after surgery for exotropia. METHODS: The goal-determined metric required surgeons to rank four possible goals preoperatively: (1) binocular potential, (2) restoration of eye contact, (3) diplopia control; and (4) torticollis management. Potential preoperative risk factors were noted. Goal-specific outcomes criteria were applied to the latest sensory-motor examination, 2-6 months after surgery. The medical records of patients who underwent surgery from 2007 to 2012 were retrospectively reviewed with respect to the goal-directed metric. RESULTS: A total of 852 patients were evaluated in the study period: 411 for restoration of eye contact; 347 for binocular potential; 78 for diplopia resolution; and16 for torticollis management. Excellent (62\%) or good (16\%) outcomes were achieved in 78\%. Procedures to resolve diplopia (OR, 6.56; 95\% CI, 3.39-12.68) and to restore eye contact (OR, 3.74; 95\% CI, 2.65-5.29) were more likely to result in excellent outcomes than procedures to improve binocular potential. Simultaneous surgery for dissociated vertical deviation (OR, 0.38; 95\% CI, 0.16-0.92) and preoperative near deviation >=50(Δ) (OR, 0.27; 95\% CI, 0.17-0.42) limited likelihood of an excellent outcome. Outcomes monitored by simultaneous rather than alternate prism and cover test were more likely graded excellent (OR, 5.16; 95\% CI, 3.50-7.62). Applying motor criteria from the binocular potential goal to the entire cohort diminished putative outcomes (P \&lt; 0.001). CONCLUSIONS: Goal-determined metric monitoring outcomes of exotropia surgery provides outcomes germane to the reason for intervention, enables analysis of risk factors affecting outcomes, and facilitates reporting on heterogeneous populations.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2015.04.009},
	author = {Chang, Yoon-Hee and Melvin, Patrice and Dagi, Linda R}
}
@article {1632295,
	title = {Glaucoma Cascade Screening in a High Risk Afro-Caribbean Haitian Population: A Pilot Study},
	journal = {J Glaucoma},
	volume = {31},
	number = {7},
	year = {2022},
	month = {2022 Jul 01},
	pages = {584-589},
	abstract = {PRCIS: Glaucoma cascade screening in first-degree relatives (FDRs) of young Haitian glaucoma patients had high yield for diagnosing manifest and suspected glaucoma in 30.8\% of those screened despite modest participation. PURPOSE: To evaluate the outcomes of glaucoma cascade screening in FDRs (parents, siblings, and offspring) of Haitian juvenile open-angle glaucoma (JOAG) patients. PATIENTS AND METHODS: Consecutive index patients (Haitians with JOAG) were identified, and the number/type of FDRs residing in South Florida were recorded. These FDRs were invited for free glaucoma screening, which included a comprehensive ophthalmic exam, gonioscopy, automated visual field testing and optical coherence tomographic analysis of the retinal nerve fiber layers. FDR characteristics and clinical findings from screening are reported. RESULTS: A total of 77 FDRs were invited, 26 (33.8\%) agreed to undergo screening (18 females, 9 males), which revealed 2 (7.7\%) with manifest glaucoma (mean age 77.5 y; one of whom was previously unaware of his glaucoma diagnosis), 6 (23.1\%) with suspected glaucoma (mean age 29.8{\textpm}18.3 y), and 18 (69.2\%) without manifest or suspected glaucoma (mean age 37.2{\textpm}21.8 y). Siblings of index patients were least likely to participate in cascade glaucoma screening when compared with index patients{\textquoteright} parents or offspring. FDR eyes with manifest glaucoma had significantly worse best-corrected visual acuities, higher intraocular pressures, thinner central corneal thicknesses, and thinner circumferential papillary retinal nerve fiber layer thicknesses than those without glaucoma. CONCLUSION: Glaucoma cascade screening of Haitian JOAG patients{\textquoteright} FDRs revealed that 30.8\% had suspected or manifest glaucoma. Future efforts centered on provider-initiated recruitment and improving public glaucoma awareness and education may increase screening participation.},
	keywords = {Adolescent, Adult, Aged, Child, Female, Glaucoma, Glaucoma, Open-Angle, Haiti, Humans, Intraocular Pressure, Male, Middle Aged, Ocular Hypertension, Pilot Projects, Tomography, Optical Coherence, Young Adult},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001996},
	author = {Chang, Ta C and Celestin, Linda and Hodapp, Elizabeth A and Grajewski, Alana L and Junk, Anna and Rothman, Adam L and Duerr, Eric R H and Swaminathan, Swarup S and Gedde, Steven J and Young, Terri L and Wiggs, Janey and Olivier, Mildred M G and Quintanilla, Raquel and Arrieta, Esdras and Savatovsky, Eleonore J and Vanner, Elizabeth A and Parrish, Richard K}
}
@article {1445330,
	title = {MACULAR ADD-ON INTRAOCULAR LENS SUCCESSFULLY RESTORES READING VISION IN EYES WITH END-STAGE DIABETIC MACULAR DISEASE},
	journal = {Retin Cases Brief Rep},
	volume = {15},
	number = {6},
	year = {2021},
	month = {2021 Nov 01},
	pages = {760-766},
	abstract = {PURPOSE: To report the outcomes of macular add-on intraocular lens implantation in improving reading vision in patients with bilateral advanced diabetic maculopathy. METHODS: In this retrospective study, a supplementary bifocal sulcus intraocular lens (Scharioth Macular Lens) was implanted in the better-seeing eye of five patients. Baseline-corrected distance vision, corrected near visual acuity, a preoperative simulation test, and multimodal imaging were collected. The primary outcome was the uncorrected near visual acuity at a working distance of 15 cm, at a 12-month follow-up. RESULTS: Study patients included 3 cases of refractory subfoveal exudation and 2 cases of diabetic macular ischemia. A preoperative test to assess the potential gain in near vision showed an improvement of >=2 paragraphs on the RADNER reading chart in all patients. At 12 months, median reading vision (corrected near visual acuity at 15 cm) significantly improved from 20/125 (range 20/50-20/200) preoperatively to uncorrected near visual acuity (at 15 cm) of 20/50 (range 20/40-20/80) (P = 0.042; Wilcoxon signed-ranks test). Distance vision remained unchanged in four patients. All patients were able to achieve the size of newsprint (20/50 Snellen equivalent), within the first 3 months. CONCLUSION: The macular add-on intraocular lens improves reading vision in visually impaired patients due to end-stage diabetic macular disease.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000885},
	author = {Chantarasorn, Yodpong and Kim, Esther L and Thabsuwan, Kittipong}
}
@article {1474220,
	title = {Choroidal Thickness Is Associated with Delayed Subretinal Fluid Absorption after Rhegmatogenous Retinal Detachment Surgery},
	journal = {Ophthalmol Retina},
	volume = {3},
	number = {11},
	year = {2019},
	month = {2019 Nov},
	pages = {947-955},
	abstract = {PURPOSE: To investigate the association between choroidal thickness and persistent subretinal fluid (PSF) after surgery for recent-onset rhegmatogenous retinal detachment (RRD). DESIGN: Case-control study. PARTICIPANTS: Fourteen eyes with macula-off RRD (with fovea on and off) that achieved retinal reattachment on funduscopy and demonstrated PSF after surgery (PSF group) were compared with 62 eyes with macula-off RRD (with fovea on and off) that did not demonstrate PSF after surgery (non-PSF group). METHODS: The diagnosis of PSF was made by the detection of subretinal fluid pockets on OCT beyond 6 weeks after surgery. Covariates included baseline demographics, duration of RRD, area of RRD, foveal status, method of subretinal fluid drainage, retinal pigment epithelium (RPE) changes, and choroidal thickness in both eyes. Multivariate regression analysis was performed by adding gender, age, and pathologic myopia into the model. The secondary outcomes included postoperative vision and time to resolution of PSF. MAIN OUTCOME MEASURES: Subfoveal choroidal thickness in affected eyes, measured by enhanced depth imaging OCT images. RESULTS: The percentage of eyes that underwent vitrectomy, scleral buckle surgery, and pneumatic retinopexy were 71.4\%, 14.3\%, and 14.3\% in the PSF group, respectively, and 87.1\%, 11.3\%, and 1.6\% in the non-PSF group, respectively. Eyes with PSF showed significantly thicker subfoveal choroid than eyes without PSF (305{\textpm}61 μm vs. 200{\textpm}70 μm, respectively; adjusted difference, 78.6{\textpm}19.1 μm; 95\% confidence interval [CI], 40.3-116.8 μm; P \&lt; 0.001). The PSF group demonstrated a greater proportion of RPE changes in fellow eyes (30.8\% vs. 1.7\%; P\&nbsp;= 0.03) and significantly worse best-corrected visual acuity at the 12-month follow-up (P\&nbsp;= 0.03). Multiple logistic regression analysis revealed that choroidal thickness of 280 μm or more was a significant factor associated with the presence of PSF (adjusted odds ratio [AOR], 13.4; 95\% CI, 3.1-34.7 [P\&nbsp;=\&nbsp;0.001]. CONCLUSIONS: Persistent subretinal fluid is associated with increased subfoveal choroidal thickness in surgical and fellow eyes and with RPE changes in the fellow eye. This indicates that PSF likely belongs to the pachychoroid spectrum. In affected eyes, PSF tends to persist for more than 1 year and results in delayed visual recovery.},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.05.009},
	author = {Chantarasorn, Yodpong and Oellers, Patrick and Eliott, Dean}
}
@article {630211,
	title = {Report of the Inaugural Meeting of the TFOS i2 = initiating innovation Series: Targeting the Unmet Need for Dry Eye Treatment (London, United Kingdom, March 21, 2015).},
	journal = {Ocul Surf},
	year = {2016},
	month = {2016 Jan 13},
	abstract = {In March 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i(2) = initiating innovation series, was sponsored by the Tear Film \&amp; Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Domp{\'e}. The TFOS i(2) meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i(2) meeting.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2015.11.003},
	author = {Chao, Wendy and Belmonte, Carlos and Benitez Del Castillo, Jos{\'e} and Bron, Anthony and Dua, Harminder and Nichols, Kelly and Novack, Gary and Schrader, Stefan and Willcox, Mark and Wolffsohn, James and Sullivan, David A}
}
@article {1653588,
	title = {An overview of peripapillary hyperreflective ovoid mass-like structures},
	journal = {Curr Opin Ophthalmol},
	volume = {33},
	number = {6},
	year = {2022},
	month = {2022 Nov 01},
	pages = {494-500},
	abstract = {PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the ophthalmic findings associated with peripapillary hyperreflective ovoid mass-like structures (PHOMS) in both adult and pediatric patients. RECENT FINDINGS: PHOMS have recently been identified in a number of different ophthalmic disease entities ranging from nonpathologic to pathologic, including but not limited to anatomic abnormalities (tilting in myopia), optic nerve head drusen, optic disc edema from inflammation (optic neuritis, white dot syndromes), vascular insults (ischemic optic neuropathy, retinal vascular occlusion), and papilledema. The mechanism underlying the formation of PHOMS has not been fully elucidated although it has been hypothesized that PHOMS occur secondary to axoplasmic stasis from crowding at the optic nerve head. SUMMARY: Although the clinical significance of the presence of PHOMS remains unclear, PHOMS are associated with several disease processes. Understanding the mechanism behind their formation and their impact on optic nerve head structure and visual function may be relevant in patients with optic nerve head pathology. The presence of PHOMS may also correlate with disease severity and duration. Future studies to evaluate whether the formation of PHOMS may be useful as an early indicator of disease or a prognostic tool are warranted.},
	keywords = {Adult, Child, Humans, Optic Disk, Optic Disk Drusen, Optic Neuritis, Papilledema, Tomography, Optical Coherence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000897},
	author = {Chapman, Jacqueline J and Heidary, Gena and Gise, Ryan}
}
@article {1445327,
	title = {Angiofibroma of the Eyelid: A Rare Clinical and Histologic Variant},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {4},
	year = {2019},
	month = {2019 Jul/Aug},
	pages = {e199-e102},
	abstract = {A flesh-colored, supraciliary lesion of the left upper eyelid in a 47-year-old man was excised for cosmetic reasons. Histopathology and immunohistochemistry demonstrated CD34-positive benign spindle cells, factor XIIIa-positive dendritic cells, and CD163-positive histiocytes, all dispersed within a diffuse collagenous background. Prominent loose perivascular cuffs of fibroblastic cells and collagen surrounded small blood vessels. Interpreted as an angiofibroma, the histopathology bore resemblance to that of a single previously-reported forearm lesion termed a "dermal fibroma with a distinctive perivascular cell arrangement." The lesion represents the first eyelid example of an unusual variant of angiofibroma.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001423},
	author = {Charles, Norman C and Jakobiec, Frederick A and Ma, Lina and Belinsky, Irina}
}
@article {1490461,
	title = {Congenital respiratory-type ciliated cyst of the lacrimal sac},
	journal = {Can J Ophthalmol},
	volume = {55},
	number = {1},
	year = {2020},
	month = {2020 Feb},
	pages = {e30-e33},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2019.05.001},
	author = {Charles, Norman C and Jakobiec, Frederick A and Chong, Jillian K and Godfrey, Kyle J and Patel, Payal and Ma, Lina}
}
@article {1603879,
	title = {Conjunctival Exophytic Schneiderian-type Papillomas: A Rare Occurrence},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2021},
	month = {2021 Jul 19},
	abstract = {Conjunctival papillomas are common tumors that exhibit an exophytic growth pattern, comprised of multiple filiform fronds of squamous epithelium that contain fibrovascular cores. The inverted (endophytic) variety of papilloma, often termed "Schneiderian," rarely occurs on the conjunctiva, with only 15 cases reported to date. Endophytic and exophytic papillomas are well described arising in the sinonasal Schneiderian epithelium where a low rate of malignant transformation may occur in the endophytic type; malignant transformation in exophytic sinonasal papillomas is exceedingly rare. The authors describe 2 cases of exophytic conjunctival papillomas with the morphology of a sinonasal or Schneiderian-type papilloma. Both were pink, sessile acquired growths in women in the sixth decade of life involving the inferior conjunctival fornix or nasal limbus. Nonkeratinizing squamous epithelium along with numerous goblet cells, intraepithelial mucinous cysts, and microabscesses were present. Immunohistochemistry showed reactivity for cytokeratin 7 and wild-type staining for p16 and p53, paralleling the findings in common conjunctival papillomas; both were also driven by low-risk human papillomavirus.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001983},
	author = {Charles, Norman C and Stagner, Anna M and Raju, Leela V and Belinsky, Irina}
}
@article {1179121,
	title = {Limbal Cysts: A Subset Exhibiting Cornea-Specific Cytokeratins},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2017},
	month = {2017 Sep 13},
	abstract = {Two cases of limbal cysts lined by nonkeratinizing epithelium were studied with a panel of cytokeratins. One was a long-standing lesion in a 30-year-old man, whereas the other was excised from a 40-year-old man following pterygium surgery. Each cyst was immunostained with a panel of cytokeratins that were specific exclusively and separately for corneal and conjunctival epithelia. The epithelial lining of each cyst was CK12 positive for corneal epithelium and CK13 negative for conjunctival epithelium. It is hypothesized that a subset of corneoscleral cysts contain corneal epithelium, probably derived from a type of limbal stem cell differentiation.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000999},
	author = {Charles, Norman C and Jakobiec, Frederick A and Zakka, Fouad R and Haberman, Ilyse D and Katikireddy, Kishore Reddy and Jurkunas, Ula V}
}
@article {1424798,
	title = {Steatocystoma Simplex of the Caruncle: Case Report and Immunohistologic Study},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {2},
	year = {2019},
	month = {2019 Mar/Apr},
	pages = {e45-e47},
	abstract = {A yellow cystic lesion of the caruncle in a 23-year-old woman proved to be a solitary steatocystoma, a rare occurrence in that location. While the histopathologic diagnosis was evident from clusters of sebaceous cells within the cyst wall, a panel of immunohistochemical stains further distinguished the lesion from a keratinous cyst. The most useful stains for differentiating the two conditions were carcinoembryonic antigen, epithelial membrane antigen, cytokeratins 17 and 19, and calretinin. Only three previous cases of caruncular steatocystoma simplex have been reported, none of which included immunohistochemical studies. The current findings support the origin of the cyst from the small duct that connects the unilobular sebaceous gland associated with vellus hairs to the follicular canal.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001321},
	author = {Charles, Norman C and Jakobiec, Frederick A and Ma, Lina and Belinsky, Irina}
}
@article {961671,
	title = {Periorbital Dermoid Cyst With Unique Trichilemmal Differentiation},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {5},
	year = {2017},
	month = {2017 Sep/Oct},
	pages = {e116-e118},
	abstract = {The authors describe a 4-year-old girl presenting with a 2-year history of a superomedial eyelid "bump" that appeared cystic on MRI. The clinical diagnosis was dermoid cyst, possibly of conjunctival origin. Following excision, histology showed a cyst that contained keratin and lanugo hairs in its lumen with sebaceous glands and chronic inflammation in its fibrous wall. An unanticipated finding was the presence of a trichilemmal (pilar) variety of epithelial lining that stained positively for calretinin, an immunostain that identifies trichilemmal epithelium. To the authors{\textquoteright} knowledge this is the first case of a dermoid cyst with trichilemmal lining. This study was conducted in compliance with the rules and regulations of the Health Insurance Portability and Accountability Act and in conformity with the Oslo declaration.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000837},
	author = {Charles, Norman C and Jakobiec, Frederick A and Patel, Payal}
}
@article {1549015,
	title = {Multicameral Steatocystoma Simplex of the Caruncle},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2020},
	month = {2020 Nov 05},
	abstract = {A yellow cyst of the caruncle in a 68-year-old man displayed the characteristic sebaceous glands and sebocytes of steatocystoma within the cyst wall, with a unique configuration of multiple branching compartments. The cyst lining was of trichilemmal character, lacking a keratohyalin granular layer, and replicated the immunohistochemical characteristics of a previously reported caruncular steatocystoma with the exception of a positive trichilemmal marker, calretinin, in the present case. Four previous cases of caruncular steatocystoma have been described, only one of which incorporated immunohistochemical analysis. Steatocystoma develops from a sebaceous gland duct, which displayed in this case multiple chambers subdividing what is usually a single round lumen.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001861},
	author = {Charles, Norman C and Jakobiec, Frederick A and Sherwood, Pamela and Belinsky, Irina}
}
@article {1773436,
	title = {Going beyond the means: Exploring the role of bias from digital determinants of health in technologies},
	journal = {PLOS Digit Health},
	volume = {2},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {e0000244},
	abstract = {BACKGROUND: In light of recent retrospective studies revealing evidence of disparities in access to medical technology and of bias in measurements, this narrative review assesses digital determinants of health (DDoH) in both technologies and medical formulae that demonstrate either evidence of bias or suboptimal performance, identifies potential mechanisms behind such bias, and proposes potential methods or avenues that can guide future efforts to address these disparities. APPROACH: Mechanisms are broadly grouped into physical and biological biases (e.g., pulse oximetry, non-contact infrared thermometry [NCIT]), interaction of human factors and cultural practices (e.g., electroencephalography [EEG]), and interpretation bias (e.g, pulmonary function tests [PFT], optical coherence tomography [OCT], and Humphrey visual field [HVF] testing). This review scope specifically excludes technologies incorporating artificial intelligence and machine learning. For each technology, we identify both clinical and research recommendations. CONCLUSIONS: Many of the DDoH mechanisms encountered in medical technologies and formulae result in lower accuracy or lower validity when applied to patients outside the initial scope of development or validation. Our clinical recommendations caution clinical users in completely trusting result validity and suggest correlating with other measurement modalities robust to the DDoH mechanism (e.g., arterial blood gas for pulse oximetry, core temperatures for NCIT). Our research recommendations suggest not only increasing diversity in development and validation, but also awareness in the modalities of diversity required (e.g., skin pigmentation for pulse oximetry but skin pigmentation and sex/hormonal variation for NCIT). By increasing diversity that better reflects patients in all scenarios of use, we can mitigate DDoH mechanisms and increase trust and validity in clinical practice and research.},
	issn = {2767-3170},
	doi = {10.1371/journal.pdig.0000244},
	author = {Marie-Laure Charpignon and Carrel, Adrien and Jiang, Yihang and Kwaga, Teddy and Cantada, Beatriz and Hyslop, Terry and Cox, Christopher E and Haines, Krista and Koomson, Valencia and Dumas, Guillaume and Morley, Michael and Dunn, Jessilyn and Ian Wong, An-Kwok}
}
@article {1351144,
	title = {AMP-activated protein kinase regulates intraocular pressure, extracellular matrix, and cytoskeleton in trabecular meshwork},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {5},
	year = {2014},
	month = {2014 Apr 08},
	pages = {3127-39},
	abstract = {PURPOSE: In this study, we investigate how adenosine monophosphate-activated protein kinase (AMPK) affects extracellular matrix (ECM) and cellular tone in the trabecular meshwork (TM), and examine how deletion of its catalytic α2 subunit affects IOP and aqueous humor clearance in mice. METHODS: Human TM tissue was examined for expression of AMPKα1 and AMPKα2, genomically distinct isoforms of the AMPK catalytic subunit. Primary cultured human TM cells were treated for 24 hours with the AMPK activator 5-amino-1-β-Dffff-ribofuranosyl-imidazole-4-carboxamide (AICAR), under basal or TGF-β2 stimulatory conditions. Conditioned media (CM) was probed for secreted protein acidic and rich in cysteine (SPARC), thrombospondin-1 (TSP-1), and ECM proteins, and cells were stained for F-actin. Cells underwent adenoviral infection with a dominant negative AMPKα subunit (ad.DN.AMPKα) and were similarly analyzed. Intraocular pressure, central corneal thickness (CCT), and aqueous clearance were measured in AMPKα2-null and wild-type (WT) mice. RESULTS: Both AMPKα1 and AMPKα2 are expressed in TM. AICAR activated AMPKα and suppressed the expression of various ECM proteins under basal and TGF-β2 stimulatory conditions. AICAR decreased F-actin staining and increased the phospho-total RhoA ratio (Ser188). Transforming growth factor-β2 transiently dephosphorylated AMPKα. Infection with ad.DN.AMPKα upregulated various ECM proteins, decreased the phospho-total RhoA ratio, and increased F-actin staining. AMPKα2-null mice exhibited 6\% higher IOP and decreased aqueous clearance compared with WT mice, without significant differences in CCT or angle morphology. CONCLUSIONS: Collectively, our data identify AMPK as a critical regulator of ECM homeostasis and cytoskeletal arrangement in the TM. Mice that are AMPKα2-null exhibit higher IOPs and decreased aqueous clearance than their WT counterparts.},
	keywords = {Adult, Aged, Aged, 80 and over, Aminoimidazole Carboxamide, AMP-Activated Protein Kinases, Animals, Aqueous Humor, Cells, Cultured, Cytoskeleton, Extracellular Matrix, Gene Deletion, Homeostasis, Humans, Intraocular Pressure, Mice, Mice, Transgenic, Phosphorylation, Protein Isoforms, Protein Subunits, Ribonucleotides, Trabecular Meshwork, Transforming Growth Factor beta2, Young Adult},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12755},
	author = {Chatterjee, Ayan and Villarreal, Guadalupe and Oh, Dong-Jin and Kang, Min Hyung and Rhee, Douglas J}
}
@article {1490442,
	title = {Multi-Omic Analyses of Growth Cones at Different Developmental Stages Provides Insight into Pathways in Adult Neuroregeneration},
	journal = {iScience},
	volume = {23},
	number = {2},
	year = {2020},
	month = {2020 Feb 21},
	pages = {100836},
	abstract = {Growth cones (GCs) are structures associated with growing neurons. GC membrane expansion, which necessitates protein-lipid interactions, is critical to axonal elongation in development and in adult neuritogenesis. We present a multi-omic analysis that integrates proteomics and lipidomics data for the identification of GC pathways, cell phenotypes, and lipid-protein interactions, with an analytic platform to facilitate the visualization of these data. We combine lipidomic data from GC and adult axonal regeneration following optic nerve crush. Our results reveal significant molecular variability in GCs across developmental ages that aligns with the upregulation and downregulation of lipid metabolic processes and correlates with distinct changes in the lipid composition of GC plasmalemma. We find that these processes also define the transition into a growth-permissive state in the adult central nervous system. The insight derived from these analyses will aid in promoting adult regeneration and functional innervation in devastating neurodegenerative diseases.},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2020.100836},
	author = {Chauhan, Muhammad Zain and Arcuri, Jennifer and Park, Kevin K and Zafar, Maroof Khan and Fatmi, Rabeet and Hackam, Abigail S and Yin, Yuqin and Benowitz, Larry and Goldberg, Jeffrey L and Samarah, Mohammad and Bhattacharya, Sanjoy K}
}
@article {439666,
	title = {PTK7+ Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1.},
	journal = {Arterioscler Thromb Vasc Biol},
	volume = {35},
	number = {7},
	year = {2015},
	month = {2015 Jul},
	pages = {1606-15},
	abstract = {OBJECTIVE: In angiogenesis, circulating mononuclear cells are recruited to vascular lesions; however, the underlying mechanisms are poorly understood. APPROACH AND RESULTS: Here, we characterize the functional role of protein tyrosine kinase 7 (PTK7)-expressing CD11b(+) mononuclear cells in vitro and in vivo using a mouse model of angiogenesis. Although the frequencies of PTK7(+)CD11b(+) cells in the bone marrow remained similar after vascular endothelial growth factor-A-induced neovascularization, we observed an 11-fold increase in the cornea. Importantly, vascular endothelial growth factor-A-induced chemotaxis of PTK7(+) cells was mediated by vascular endothelial growth factor receptor 2. In a coculture with endothelial cells, PTK7(+)CD11b(+) cells stabilized the vascular network for 2 weeks by expressing high levels of angiopoietin-1. The enhanced vascular stability was abolished by knockdown of angiopoietin-1 in PTK7(+)CD11b(+) cells and could be restored by angiopoietin-1 treatment. CONCLUSIONS: We conclude that PTK7 expression in perivascular mononuclear cells induces vascular endothelial growth factor receptor 2 and angiopoietin-1 expression and thus contributes to vascular stabilization in angiogenesis.},
	issn = {1524-4636},
	doi = {10.1161/ATVBAHA.114.305228},
	author = {Chauhan, Sunil K and Lee, Hyung Keun and Lee, Hyun Soo and Park, Eun Young and Jeong, Eunae and Dana, Reza}
}
@article {303846,
	title = {Quantification of allospecific and nonspecific corneal endothelial cell damage after corneal transplantation.},
	journal = {Eye (Lond)},
	volume = {29},
	number = {1},
	year = {2015},
	month = {2015 Jan},
	pages = {136-44},
	abstract = {PURPOSE: To investigate the effect of host immunity (allospecific) and surgical manipulation (non-allospecific) on corneal endothelial cells (CECs) in corneal transplantation. METHODS: Draining lymph nodes and grafted C57BL/6 corneas were harvested from syngeneic recipients, allograft acceptors, and allograft rejectors (BALB/c) 1, 3, and 8 weeks after transplantation. We analyzed CEC apoptosis using an ex vivo cornea-in-the-cup assay, and visualized cell-to-cell junctions using immunohistochemical staining (ZO-1). Automatic cell analysis using Confoscan software was used to measure CEC density as well as changes in CEC morphology by quantifying the coefficient of variation in cell size (polymegethism) and shape (pleomorphism). RESULTS: The cornea-in-the-cup assay showed that allogeneic acceptor T cells and to an even greater extent rejector T cells (but not syngeneic T cells) induced CEC apoptosis. CEC density after corneal transplantation was significantly reduced in allogeneic acceptors compared with syngeneic grafts (P\&lt;0.001), and CEC density was even further reduced in the allo-rejector group compared with the allo-acceptor group. Allogeneic grafts showed a greater increase in the coefficient of variation in cell size (polymegethism) when compared with syngeneic grafts 1 week after transplantation (P=P\&lt;0.001). However, pleomorphism was not significantly different between syngeneic and allo-acceptor grafts, indicating that polymegethism (but not pleomorphism or cell density) is a sensitive indicator of the effect of alloimmunity on CECs. CONCLUSIONS: Our data demonstrate that host alloimmunity rather than surgical manipulation alone is the major cause of CEC damage in corneal transplantation, and such morphologic changes of CECs can be detected before the clinically visible onset of allograft rejection.},
	issn = {1476-5454},
	doi = {10.1038/eye.2014.248},
	author = {Chauhan, S K and Jurkunas, U and Funaki, T and Dastjerdi, M and Dana, R}
}
@article {935666,
	title = {The Role of Vitrectomy in the Management of Fungal Endophthalmitis.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	month = {2017},
	pages = {29-35},
	abstract = {Fungal endophthalmitis is an important cause of vision loss worldwide with a large body of literature describing the treatment of the disease. The evidence supporting the use of pars plana vitrectomy in the management of fungal endophthalmitis is largely comprised of case reports and case series and demonstrates the important role of vitrectomy surgery. Vitrectomy can improve the likelihood of establishing the diagnosis, enhance the treatment of infection by removing fungal elements in the vitreous, aid in the removal of other inoculated intraocular structures, and is an important tool in the management of vision-threatening post-infectious sequelae like retinal detachment and epiretinal membrane.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228396},
	author = {Chee, Yewlin E and Eliott, Dean}
}
@article {416851,
	title = {Improving the Teaching Skills of Residents in a Surgical Training Program: Results of the Pilot Year of a Curricular Initiative in an Ophthalmology Residency Program.},
	journal = {J Surg Educ},
	volume = {72},
	number = {5},
	year = {2015},
	month = {2015 Sep-Oct},
	pages = {890-7},
	abstract = {OBJECTIVE: To design and implement a teaching skills curriculum that addressed the needs of an ophthalmology residency training program, to assess the effect of the curriculum, and to present important lessons learned. DESIGN: A teaching skills curriculum was designed for the Harvard Medical School (HMS) Residency Training Program in Ophthalmology. Results of a needs assessment survey were used to guide curriculum objectives. Overall, 3 teaching workshops were conducted between October 2012 and March 2013 that addressed areas of need, including procedural teaching. A postcurriculum survey was used to assess the effect of the curriculum. SETTING: Massachusetts Eye and Ear Infirmary, a tertiary care institution in Boston, MA. PARTICIPANTS: Overall, 24 residents in the HMS Residency Training Program in Ophthalmology were included. RESULTS: The needs assessment survey demonstrated that although most residents anticipated that teaching would be important in their future career, only one-third had prior formal training in teaching. All residents reported they found the teaching workshops to be either very or extremely useful. All residents reported they would like further training in teaching, with most residents requesting additional training in best procedural teaching practices for future sessions. CONCLUSIONS: The pilot year of the resident-as-teacher curriculum for the HMS Residency Training Program in Ophthalmology demonstrated a need for this curriculum and was perceived as beneficial by the residents, who reported increased comfort in their teaching skills after attending the workshops.},
	issn = {1878-7452},
	doi = {10.1016/j.jsurg.2015.03.002},
	author = {Chee, Yewlin E and Newman, Lori R and Loewenstein, John I and Kloek, Carolyn E}
}
@article {280926,
	title = {Quantitative assessment of central retinal thickness in recurrent neovascular age-related macular degeneration},
	journal = {Br J Ophthalmol},
	volume = {98},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1308},
	keywords = {Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Female, Humans, Male, Ranibizumab, Retina, Visual Acuity, Wet Macular Degeneration},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-305673},
	author = {Chee Yee, Chan and Papakostas, Thanos D and Vavvas, Demetrios G}
}
@article {1460378,
	title = {Late-onset retinal degeneration pathology due to mutations in CTRP5 is mediated through HTRA1},
	journal = {Aging Cell},
	volume = {18},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {e13011},
	abstract = {Late-onset retinal degeneration (L-ORD) is an autosomal dominant macular degeneration characterized by the formation of sub-retinal pigment epithelium (RPE) deposits and neuroretinal atrophy. L-ORD results from mutations in the C1q-tumor necrosis factor-5 protein (CTRP5), encoded by the CTRP5/C1QTNF5 gene. To understand the mechanism underlying L-ORD pathology, we used a human cDNA library yeast two-hybrid screen to identify interacting partners of CTRP5. Additionally, we analyzed the Bruch{\textquoteright}s membrane/choroid (BM-Ch) from wild-type (Wt), heterozygous S163R Ctrp5 mutation knock-in (Ctrp5 ), and homozygous knock-in (Ctrp5 ) mice using mass spectrometry. Both approaches showed an association between CTRP5 and HTRA1 via its C-terminal PDZ-binding motif, stimulation of the HTRA1 protease activity by CTRP5, and CTRP5 serving as an HTRA1 substrate. The S163R-CTRP5 protein also binds to HTRA1 but is resistant to HTRA1-mediated cleavage. Immunohistochemistry and proteomic analysis showed significant accumulation of CTRP5 and HTRA1 in BM-Ch of Ctrp5 and Ctrp5 mice compared with Wt. Additional extracellular matrix (ECM) components that are HTRA1 substrates also accumulated in these mice. These results implicate HTRA1 and its interaction with CTRP5 in L-ORD pathology.},
	issn = {1474-9726},
	doi = {10.1111/acel.13011},
	author = {Chekuri, Anil and Zientara-Rytter, Katarzyna and Soto-Hermida, Angel and Borooah, Shyamanga and Voronchikhina, Marina and Biswas, Pooja and Kumar, Virender and Goodsell, David and Hayward, Caroline and Shaw, Peter and Stanton, Chloe and Garland, Donita and Subramani, Suresh and Ayyagari, Radha}
}
@article {1806696,
	title = {Unilateral Internuclear Ophthalmoplegia and Upbeat Nystagmus Due to a Rapidly Enlarging Cavernous Malformation and Associated Developmental Venous Anomaly},
	journal = {J Neuroophthalmol},
	year = {2024},
	month = {2024 Feb 20},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000002107},
	author = {Chen, Amalie and Quinn, Carson and Alexander, Michael J and Rizzo, Joseph F and Matiello, Marcelo}
}
@article {1762026,
	title = {Seeing Past the Disc},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 Sep 04},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000002003},
	author = {Chen, Amalie and Gluckstein, Jeffrey A and Gittinger, John W}
}
@article {1445342,
	title = {Are BALB/c Mice Relevant Models for Understanding Sex-Related Differences in Gene Expression in the Human Meibomian Gland?},
	journal = {Cornea},
	volume = {38},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {1554-1562},
	abstract = {BACKGROUND: A compelling feature of dry eye disease is that it occurs predominantly in women. We hypothesize that this female prevalence is linked to sex-related differences in the meibomian gland (MG). This gland plays a critical role in maintaining the tear film, and its dysfunction is a major cause of dry eye disease. To understand the factors that underlie MG sexual dimorphism and promote dry eye in women, we seek to identify an optimal model for the human MG. Our goal was to determine whether a murine MG is such a model. Toward that end, we examined whether sex differences in MG gene expression are the same in BALB/c mice and humans. METHODS: Eyelid tissues were collected from humans (n = 5-7/sex) and BALB/c mice (n = 9/sex). MGs were isolated and processed for the evaluation of gene expression by using microarrays and bioinformatics software. RESULTS: Our analysis of the 500 most highly expressed genes from human and mouse MGs showed that only 24.4\% were the same. Our comparison of 100 genes with the greatest sex-associated differences in human and mouse MGs demonstrated that none were the same. Sex also exerted a significant impact on numerous ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, and chromosomes, but these effects were primarily species-specific. CONCLUSIONS: Our results indicate that BALB/c mice are not optimal models for understanding sex-related differences in gene expression of the human MG.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002017},
	author = {Chen, Xiaomin and Sullivan, Benjamin D and Rahimi Darabad, Raheleh and Liu, Shaohui and Kam, Wendy R and Sullivan, David A}
}
@article {1351146,
	title = {Chronic dry eye disease is principally mediated by effector memory Th17 cells},
	journal = {Mucosal Immunol},
	volume = {7},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {38-45},
	abstract = {Recent experimental and clinical data suggest that there is a link between dry eye disease (DED) and T-cell-mediated immunity. However, whether these immune responses are a consequence or cause of ocular surface inflammation remains to be determined. Thus far, only models of acute DED have been used to derive experimental data. This is in contrast to clinical DED which usually presents as a chronic disease. In the present study, using a murine model of chronic DED, it was established that the chronic phase of the disease is accompanied by T helper type 17 (Th17) responses at the ocular surface and that a significant memory T-cell population can be recovered from chronic DED. This memory response is predominantly mediated by Th17 cells. Moreover, adoptive transfer of this memory T-cell population was shown to induce more severe and rapidly progressing DED than did the adoptive transfer of its effector or naive counterparts. Not only do these results clearly demonstrate that effector memory Th17 cells are primarily responsible for maintaining the chronic and relapsing course of DED, but they also highlight a potentially novel therapeutic strategy for targeting memory immune responses in patients with DED. },
	keywords = {Adoptive Transfer, Animals, Chronic Disease, Disease Models, Animal, Dry Eye Syndromes, Eye, Female, Humans, Immunologic Memory, Inflammation, Mice, T-Lymphocyte Subsets, Th17 Cells},
	issn = {1935-3456},
	doi = {10.1038/mi.2013.20},
	author = {Chen, Y. and Chauhan, S K and Lee, H Soo and Saban, D R and Dana, R}
}
@article {313111,
	title = {Pediatric glaucoma surgery: a report by the American Academy Of Ophthalmology},
	journal = {Ophthalmology},
	volume = {121},
	number = {11},
	year = {2014},
	month = {2014 Nov},
	pages = {2107-15},
	abstract = {OBJECTIVE: To review the current published literature to evaluate the success rates and long-term problems associated with surgery for pediatric glaucoma. METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted in May 2012. The search yielded 838 potentially relevant citations, of which 273 were in non-English languages. The titles and abstracts of these articles were reviewed by the authors, and 364 were selected for possible further review. Members of the Ophthalmic Technology Assessment Committee Glaucoma Panel reviewed the full text of these articles and used the 36 that met inclusion and exclusion criteria for this Ophthalmic Technology Assessment. There were no studies on the topic that provided level I evidence. The assessment included only level II and level III studies. RESULTS: Surgeons treat pediatric glaucoma most commonly with goniotomy, trabeculotomy, trabeculectomy, combined trabeculotomy and trabeculectomy, tube shunt surgery, cyclodestruction, and deep sclerectomy. Certain surgical options seem better for specific diagnoses, such as primary congenital glaucoma, aphakic glaucoma, and glaucomas associated with other ocular or systemic anomalies. CONCLUSIONS: There are many surgical options for the treatment of the pediatric glaucomas. The relative efficacy of these various procedures for particular diagnoses and clinical situations should be weighed against the specific risks associated with the procedures for individual patients.},
	keywords = {Academies and Institutes, Adolescent, Child, Child, Preschool, Filtering Surgery, Glaucoma, Glaucoma Drainage Implants, Humans, Infant, Intraocular Pressure, Ophthalmology, Technology Assessment, Biomedical, Trabeculectomy, Treatment Outcome, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.05.010},
	author = {Chen, Teresa C and Chen, Philip P and Francis, Brian A and Junk, Anna K and Smith, Scott D and Singh, Kuldev and Lin, Shan C}
}
@article {1615227,
	title = {Autoimmunity in dry eye disease - An updated review of evidence on effector and memory Th17 cells in disease pathogenicity},
	journal = {Autoimmun Rev},
	volume = {20},
	number = {11},
	year = {2021},
	month = {2021 Nov},
	pages = {102933},
	abstract = {The classic Th1/Th2 dogma has been significantly reshaped since the subsequent introduction of several new T helper cell subsets, among which the most intensively investigated during the last decade is the Th17 lineage that demonstrates critical pathogenic roles in autoimmunity and chronic inflammation - including the highly prevalent dry eye disease. In this review, we summarize current concepts of Th17-mediated disruption of ocular surface immune homeostasis that leads to autoimmune inflammatory dry eye disease, by discussing the induction, activation, differentiation, migration, and function of effector Th17 cells in disease development, highlighting the phenotypic and functional plasticity of Th17 lineage throughout the disease initiation, perpetuation and sustention. Furthermore, we emphasize the most recent advance in Th17 memory formation and function in the chronic course of dry eye disease, a major area to be better understood for facilitating the development of effective treatments in a broader field of autoimmune diseases that usually present a chronic course with recurrent episodes of flare in the target tissues or organs.},
	keywords = {Autoimmune Diseases, Autoimmunity, Dry Eye Syndromes, Humans, Th17 Cells, Virulence},
	issn = {1873-0183},
	doi = {10.1016/j.autrev.2021.102933},
	author = {Chen, Yihe and Dana, Reza}
}
@article {1814371,
	title = {Update on Neuro-ophthalmic Manifestations of Immune Checkpoint Inhibitors},
	journal = {Curr Neurol Neurosci Rep},
	year = {2024},
	month = {2024 Mar 18},
	abstract = {PURPOSE OF REVIEW: Immune checkpoint inhibitor (ICI) use has been on the rise for treatment of many different malignancies. Subsequently, more has been learned about immune-related adverse events (irAEs) that occur up to 12\&nbsp;months after treatment. This review summarizes the latest findings and management of neuro-ophthalmic associated irAEs. RECENT FINDINGS: irAEs can affect the afferent and efferent neuro-ophthalmic pathways, thereby targeting central and peripheral nervous systems. As more cases are being reported, it is becoming apparent that neuro-ophthalmic irAEs often present with atypical features when compared to their spontaneous autoimmune counterparts. These neuro-ophthalmic presentations can also be signs of a more extensive inflammatory process that spans other organ systems, such as myopathies, endocrinopathies, and paraneoplastic syndromes. Awareness of neuro-ophthalmic irAEs and their atypical presentations can lead to early detection, termination of ICI treatment, and immunosuppressant therapy initiation.},
	issn = {1534-6293},
	doi = {10.1007/s11910-024-01336-z},
	author = {Chen, Amalie and Chwalisz, Bart K}
}
@article {1504083,
	title = {Private Equity in Ophthalmology and Optometry: Analysis of Acquisitions from 2012 through 2019 in the United States},
	journal = {Ophthalmology},
	volume = {127},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {445-455},
	abstract = {PURPOSE: To identify temporal and geographic trends in private equity (PE)-backed acquisitions of ophthalmology and optometry practices in the United States. DESIGN: A cross-sectional study using private equity acquisition and investment data from January 1, 2012, through October 20,\&nbsp;2019. PARTICIPANTS: A total of 228 PE acquisitions of ophthalmology and optometry practices in the United States between 2012 and\&nbsp;2019. METHODS: Acquisition and financial investment data were compiled from 6 financial databases, 4 industry news outlets, and publicly available press releases from PE firms or platform companies. MAIN OUTCOME MEASURES: Yearly trends in ophthalmology and optometry acquisitions, including number of total acquisitions, clinical locations, and providers of acquired practices as well as subsequent sales, median holding period, geographic footprint, and financing status of each platform company. RESULTS: A total of 228 practices associated with 1466 clinical locations and 2146 ophthalmologists or optometrists were acquired by 29 PE-backed platform companies. Of these acquisitions, 127, 9, and 92 were comprehensive or multispecialty, retina, and optometry practices, respectively. Acquisitions increased rapidly between 2012 and 2019: 42 practices were acquired between 2012 and 2016 compared to 186 from 2017 through 2019. Financing rounds of platform companies paralleled temporal acquisition trends. Three platform companies, comprising 60\% of platforms formed before 2016, were subsequently sold or recapitalized to new PE investors by the end of this study period with a median holding period of 3.5 years. In terms of geographic distribution, acquisitions occurred in 40 states with most PE firms developing multistate platform companies. New York and California were the 2 states with the greatest number of PE acquisitions with 22 and 19, respectively. CONCLUSIONS: Private equity-backed acquisitions of ophthalmology and optometry practices have increased rapidly since 2012, with some platform companies having already been sold or recapitalized to new investors. Additionally, private equity-backed platform companies have developed both regionally focused and multistate models of add-on acquisitions. Future research should assess the impact of PE investment on patient, provider, and practice metrics, including health outcomes, expenditures, procedural volume, and staff employment.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.01.007},
	author = {Chen, Evan M and Cox, Jacob T and Begaj, Tedi and Armstrong, Grayson W and Khurana, Rahul N and Parikh, Ravi}
}
@article {1302164,
	title = {Toxicity of cosmetic preservatives on human ocular surface and adnexal cells},
	journal = {Exp Eye Res},
	year = {2018},
	month = {2018 Feb 24},
	abstract = {Cosmetic products, such as mascara, eye shadow, eyeliner and eye makeup remover are used extensively to highlight the eyes or clean the eyelids, and typically contain preservatives to prevent microbial growth. These preservatives include benzalkonium chloride (BAK) and formaldehyde (FA)-releasing preservatives. We hypothesize that these preservatives, at concentrations (BAK = 1 mg/ml; FA = 0.74 mg/ml) approved for consumer use, are toxic to human ocular surface and adnexal cells. Accordingly, we tested the influence of BAK and FA on the morphology, survival, and proliferation and signaling ability of immortalized human meibomian gland (iHMGECs), corneal (iHCECs) and conjunctival (iHConjECs) epithelial cells. iHMGECs, iHCECs and iHConjECs were cultured with different concentrations of BAK (5 μg/ml to 0.005 μg/ml) or FA (1 mg/ml to 1 μg/ml) under basal, proliferating or differentiating conditions up to 7 days. We used low BAK levels, because we found that 0.5 mg/ml and 50 μg/ml BAK killed iHMGECs within 1 day after a 15 min exposure. Experimental procedures included analyses of cell appearance, cell number, and neutral lipid content (LipidTox), lysosome accumulation (LysoTracker) and AKT signaling in all 3 cell types. Our results demonstrate that BAK and FA cause dose-dependent changes in the morphology, survival, proliferation and AKT signaling of iHMGECs, iHCECs and iHConjECs. Many of the concentrations tested induced cell atrophy, poor adherence, decreased proliferation and death, after 5 days of exposure. Cellular signaling, as indicated by AKT phosphorylation after 15 (FA) or 30 (BAK) minutes of treatment, was also reduced in a dose-dependent fashion in all 3 cell types, irrespective of whether cells had been cultured under proliferating or differentiating conditions. Our results support our hypothesis and demonstrate that the cosmetic preservatives, BAK and FA, exert many toxic effects on cells of the ocular surface and adnexa.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.02.020},
	author = {Chen, Xiaomin and Sullivan, David A and Sullivan, Amy Gallant and Kam, Wendy R and Liu, Yang}
}
@article {1363253,
	title = {Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy},
	journal = {Angiogenesis},
	volume = {16},
	number = {4},
	year = {2013},
	month = {2013 Oct},
	pages = {985-92},
	abstract = {Regeneration of blood vessels in ischemic neuronal tissue is critical to reduce tissue damage in diseases. In proliferative retinopathy, initial vessel loss leads to retinal ischemia, which can induce either regrowth of vessels to restore normal metabolism and minimize damage, or progress to hypoxia-induced sight-threatening pathologic vaso-proliferation. It is not well understood how retinal neurons mediate regeneration of vascular growth in response to ischemic insults. In this study we aim to investigate the potential role of Sirtuin 1 (Sirt1), a metabolically-regulated protein deacetylase, in mediating the response of ischemic neurons to regulate vascular regrowth in a mouse model of oxygen-induced ischemic retinopathy (OIR). We found that Sirt1 is highly induced in the avascular ischemic retina in OIR. Conditional depletion of neuronal Sirt1 leads to significantly decreased retinal vascular regeneration into the avascular zone and increased hypoxia-induced pathologic vascular growth. This effect is likely independent of PGC-1α, a known Sirt1 target, as absence of PGC-1α in knockout mice does not impact vascular growth in retinopathy. We found that neuronal Sirt1 controls vascular regrowth in part through modulating deacetylation and stability of hypoxia-induced factor 1α and 2α, and thereby modulating expression of angiogenic factors. These results indicate that ischemic neurons induce Sirt1 to promote revascularization into ischemic neuronal areas, suggesting a novel role of neuronal Sirt1 in mediating vascular regeneration in ischemic conditions, with potential implications beyond retinopathy.},
	keywords = {Angiogenic Proteins, Animals, Animals, Newborn, Basic Helix-Loop-Helix Transcription Factors, Carbazoles, Cell Line, Disease Models, Animal, Ischemia, Mice, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Physiologic, Neurons, Organ Culture Techniques, Oxygen, Oxygen Inhalation Therapy, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Protein Processing, Post-Translational, Regeneration, Retinal Ganglion Cells, Retinal Vessels, Retinopathy of Prematurity, RNA, Messenger, Sirtuin 1, Transcription Factors, Up-Regulation},
	issn = {1573-7209},
	doi = {10.1007/s10456-013-9374-5},
	author = {Chen, Jing and Michan, Shaday and Juan, Aimee M and Hurst, Christian G and Hatton, Colman J and Pei, Dorothy T and Joyal, Jean-Sebastien and Evans, Lucy P and Cui, Zhenghao and Stahl, Andreas and Sapieha, Przemyslaw and Sinclair, David A and Smith, Lois E H}
}
@article {1532339,
	title = {Preoperative Medical Testing and Falls in Medicare Beneficiaries Awaiting Cataract Surgery},
	journal = {Ophthalmology},
	volume = {128},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {208-215},
	abstract = {PURPOSE: Delaying cataract surgery is associated with an increased risk of falls, but whether routine preoperative testing delays cataract surgery long enough to cause clinical harm is unknown. We sought to determine whether the use of routine preoperative testing leads to harm in the form of delayed surgery and falls in Medicare beneficiaries awaiting cataract surgery. DESIGN: Retrospective, observational cohort study using 2006-2014 Medicare claims. PARTICIPANTS: Medicare beneficiaries 66+ years of age with a Current Procedural Terminology claim for ocular biometry. METHODS: We measured the mean and median number of days between biometry and cataract surgery, calculated the proportion of patients waiting >= 30 days or >= 90 days for surgery, and determined the odds of sustaining a fall within 90 days of biometry among patients of high-testing physicians (testing performed in >= 75\% of their patients) compared with patients of low-testing physicians. We also estimated the number of days of delay attributable to high-testing physicians. MAIN OUTCOME MEASURES: Incidence of falls occurring between biometry and surgery, odds of falling within 90 days of biometry, and estimated delay associated with physician testing behavior. RESULTS: Of 248 345 beneficiaries, 16.4\% were patients of high-testing physicians. More patients of high-testing physicians waited >= 30 days and >= 90 days to undergo surgery (31.4\% and 8.2\% vs. 25.0\% and 5.5\%, respectively; P \&lt; 0.0001 for both). Falls before surgery in patients of high-testing physicians increased by 43\% within the 90 days after ocular biometry (1.0\% vs. 0.7\%; P \&lt; 0.0001). The adjusted odds ratio of falling within 90 days of biometry in patients of high-testing physicians versus low-testing physicians was 1.10 (95\% confidence interval [CI], 1.03-1.19; P\&nbsp;= 0.008). After adjusting for surgical wait time, the odds ratio decreased to 1.07 (95\% CI, 1.00-1.15; P\&nbsp;= 0.06). The delay associated with having a high-testing physician was approximately 8 days (estimate, 7.97 days; 95\% CI, 6.40-9.55 days; P \&lt; 0.0001). Other factors associated with delayed surgery included patient race (non-White), Northeast region, ophthalmologist <= 40 years of age, and low surgical volume. CONCLUSIONS: Overuse of routine preoperative medical testing by high-testing physicians is associated with delayed surgery and increased falls in cataract patients awaiting surgery.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.09.013},
	author = {Chen, Catherine L and McLeod, Stephen D and Lietman, Thomas M and Shen, Hui and Boscardin, W John and Peggy Chang, Han-Ying and Whooley, Mary A and Gelb, Adrian W and Lee, Sei J and Dudley, R Adams}
}
@article {1364593,
	title = {Retinal expression of Wnt-pathway mediated genes in low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice},
	journal = {PLoS One},
	volume = {7},
	number = {1},
	year = {2012},
	month = {2012},
	pages = {e30203},
	abstract = {Mutations in low-density lipoprotein receptor-related protein 5 (Lrp5) impair retinal angiogenesis in patients with familial exudative vitreoretinopathy (FEVR), a rare type of blinding vascular eye disease. The defective retinal vasculature phenotype in human FEVR patients is recapitulated in Lrp5 knockout (Lrp5(-/-)) mouse with delayed and incomplete development of retinal vessels. In this study we examined gene expression changes in the developing Lrp5(-/-) mouse retina to gain insight into the molecular mechanisms that underlie the pathology of FEVR in humans. Gene expression levels were assessed with an Illumina microarray on total RNA from Lrp5(-/-) and WT retinas isolated on postnatal day (P) 8. Regulated genes were confirmed using RT-qPCR analysis. Consistent with a role in vascular development, we identified expression changes in genes involved in cell-cell adhesion, blood vessel morphogenesis and membrane transport in Lrp5(-/-) retina compared to WT retina. In particular, tight junction protein claudin5 and amino acid transporter slc38a5 are both highly down-regulated in Lrp5(-/-) retina. Similarly, several Wnt ligands including Wnt7b show decreased expression levels. Plasmalemma vesicle associated protein (plvap), an endothelial permeability marker, in contrast, is up-regulated consistent with increased permeability in Lrp5(-/-) retinas. Together these data suggest that Lrp5 regulates multiple groups of genes that influence retinal angiogenesis and may contribute to the pathogenesis of FEVR.},
	keywords = {Adaptor Proteins, Signal Transducing, Amino Acid Transport Systems, Neutral, Animals, Carrier Proteins, Disease Models, Animal, Dishevelled Proteins, Eye Proteins, Frizzled Receptors, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Low Density Lipoprotein Receptor-Related Protein-5, Membrane Proteins, Mice, Mice, Knockout, Nerve Tissue Proteins, Oligonucleotide Array Sequence Analysis, Phosphoproteins, Proto-Oncogene Proteins, Retina, Retinal Vessels, Reverse Transcriptase Polymerase Chain Reaction, Vitreoretinopathy, Proliferative, Wnt Proteins, Wnt Signaling Pathway},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0030203},
	author = {Chen, Jing and Stahl, Andreas and Krah, Nathan M and Seaward, Molly R and Joyal, Jean-Sebastian and Juan, Aimee M and Hatton, Colman J and Aderman, Christopher M and Dennison, Roberta J and Willett, Keirnan L and Sapieha, Przemyslaw and Smith, Lois E H}
}
@article {1532369,
	title = {Effects of Terpinen-4-ol on Meibomian Gland Epithelial Cells In Vitro},
	journal = {Cornea},
	volume = {39},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {1541-1546},
	abstract = {PURPOSE: Infestation with demodex mites has been linked to the development of chalazion, meibomian gland dysfunction, and blepharitis. An effective treatment is the eyelid application of terpinen-4-ol (T4O), a tea tree oil component. However, T4O is also known to be toxic to nonocular epithelial cells. We hypothesize that T4O toxicity also extends to human meibomian gland epithelial cells (HMGECs). METHODS: Immortalized (I) HMGECs were cultured with varying concentrations (1.0\%-0.001\%) of T4O under proliferating or differentiating conditions up to 5 days. Experimental procedures included analyses of cell appearance, survival, P-Akt signaling, lysosome accumulation, and neutral lipid content. RESULTS: Our findings show that T4O causes a dose- and time-dependent decrease in the cell survival of IHMGECs. After 15 minutes of exposure to 1\% T4O, IHMGECs exhibited rounding, atrophy, and poor adherence. Within 90 minutes of such treatment, almost all cells died. Reducing the T4O concentration to 0.1\% also led to a marked decrease in P-Akt signaling and cell survival of IHMGECs. Decreasing the T4O amount to 0.01\% caused a slight, but significant, reduction in the IHMGEC number after 5 days of culture and did not influence the ability of these cells to differentiate. CONCLUSIONS: T4O, even at levels 10-fold to 100-fold lower than demodicidal concentrations, is toxic to HMGECs in vitro.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002506},
	author = {Chen, Di and Wang, Jingyi and Sullivan, David A and Kam, Wendy R and Liu, Yang}
}
@article {1043211,
	title = {Pathogenic Role of MicroRNA-21 in Diabetic Retinopathy Through Down-Regulation of PPARα},
	journal = {Diabetes},
	year = {2017},
	month = {2017 Mar 07},
	abstract = {Fenofibrate, a specific agonist of peroxisome proliferator-activated receptor alpha (PPARα), displays robust therapeutic effects on diabetic retinopathy (DR) in type 2 diabetic patients. Our recent studies have shown that PPARα is down-regulated in the diabetic retina, which contributes to the pathogenesis of DR. However, the mechanism for diabetes-induced down-regulation of PPARα remains unknown. We investigated the role of microRNA-21 (miR-21) in regulating PPARα in DR. MiR-21 was over-expressed, while PPARα levels were decreased in the retina of db/db mice, a type 2 diabetic model. Such alterations were also observed in palmitate-treated retinal endothelial cells. MiR-21 targeted PPARα by inhibiting its mRNA translation. Knockout of miR-21 prevented the decrease of PPARα, alleviated microvascular damage, ameliorated inflammation and reduced cell apoptosis in the retina of db/db mice. Intravitreal injection of miR-21 inhibitor attenuated PPARα down-regulation and ameliorated retinal inflammation in db/db mice. Further, retinal miR-21 levels were increased, while PPARα levels were decreased in oxygen-induced retinopathy (OIR). Knockout of miR-21 prevented PPARα down-regulation and ameliorated retinal neovascularization and inflammation in OIR retinas. In conclusion, diabetes-induced over-expression of miR-21 in the retina is responsible, at least in part, for PPARα down-regulation in DR. Targeting miR-21 may represent a novel therapeutic strategy for DR.},
	issn = {1939-327X},
	doi = {10.2337/db16-1246},
	author = {Chen, Qian and Qiu, Fangfang and Zhou, Kelu and Matlock, H Greg and Takahashi, Yusuke and Rajala, Raju V S and Yang, Yanhui and Moran, Elizabeth and Ma, Jian-Xing}
}
@article {1632280,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {129},
	number = {2},
	year = {2022},
	month = {2022 02},
	pages = {e33-e35},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.10.005},
	author = {Chen, Stephanie P and Azad, Amee D and Pershing, Suzann}
}
@article {1295856,
	title = {A Revised Estimate of Costs Associated With Routine Preoperative Testing in Medicare Cataract Patients With a Procedure-Specific Indicator},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {3},
	year = {2018},
	month = {2018 Mar 01},
	pages = {231-238},
	abstract = {Importance: Routine preoperative medical testing is not recommended for patients undergoing low-risk surgery, but testing is common before surgery. A 30-day preoperative testing window is conventionally used for study purposes; however, the extent of routine testing that occurs prior to that point is unknown.

Objective: To improve on existing cost estimates by identifying all routine preoperative testing that takes place after the decision is made to perform cataract surgery.

Design, Setting, and Participants: This cross-sectional study assessed preoperative care in a 50\% sample of Medicare beneficiaries older than 66 years who underwent ambulatory cataract surgery in 2011. Data analysis was completed from March 2016 to October 2017.

Main Outcomes and Measures: Using ocular biometry as a procedure-specific indicator to mark the start of the routine preoperative testing window, we measured testing rates in the interval between ocular biometry and cataract surgery and compared this with testing rates in the 6 months preceding biometry. We estimated the total cost of testing that occurred between biometry and cataract surgery.

Results: A total of 440 857 patients underwent cataract surgery. A total of 423 710 (96.1\%) had an ocular biometry claim before index surgery, of whom 264 514 (60.0\%) were female; the mean (SD) age of the cohort was 76.1 (6.2) years. A total of 111 998 (25.4\%) underwent surgery more than 30 days after biometry. Among patients with a biometry claim, the mean number of tests/patient/month increased from 1.1 in the baseline period to 1.7 in the interval between biometry and cataract surgery. Although preoperative testing peaked in all patients in the 30 days preceding surgery (1.8 tests/patient/month), the subset of patients with no overlap between postbiometry and presurgery periods experienced increased testing rates to 1.8 tests per patient per month in the 30 days after biometry, regardless of the elapsed time between biometry and surgery. The total estimated cost of routine preoperative testing in the full cohort was $22.7 million; we estimate that routine preoperative testing costs Medicare up to $45.4 million annually.

Conclusions and Relevance: In this study of Medicare beneficiaries, routine preoperative medical testing occurs more often and is costlier than has been reported previously. Extra costs are attributable to testing that occurs prior to the 30-day window preceding surgery. As a cost-cutting measure, routine preoperative medical testing should be avoided in patients with cataracts throughout the interval between ocular biometry and cataract surgery.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.6372},
	author = {Chen, Catherine L and Clay, Theodore H and McLeod, Stephen and Peggy Chang, Han-Ying and Gelb, Adrian W and Dudley, R Adams}
}
@article {1323921,
	title = {A Cross-Sectional Observational Study of Nailfold Capillary Morphology in Uveitis},
	journal = {Curr Eye Res},
	volume = {43},
	number = {11},
	year = {2018},
	month = {2018 Nov},
	pages = {1342-1350},
	abstract = {PURPOSE: We performed nailfold capillary microscopy to explore microvasculature abnormalities in uveitis overall and uveitis stratified in various ways. METHODS: This was a cross-sectional, case-control, observational study. One hundred and seven uveitis patients and 130 control subjects were included. We used a JH-1004 capillaroscope to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject{\textquoteright}s nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops \&gt;\&nbsp;25\&nbsp;{\textmu}m, and avascular zones \&gt;\&nbsp;200\&nbsp;{\textmu}m. Univariate analyses were used for the assessment of case-control morphological differences and multivariate analyses were performed to assess the relation between nailfold capillaroscopic findings and uveitis subgroups. RESULTS: In univariate analysis, uveitis patients were more likely to have higher tortuosity ratings and reduced capillary density compared to controls (p\&nbsp;\&lt;\&nbsp;0.001 for both); furthermore, dilated capillary loops, avascular zone and hemorrhages were more frequent in uveitis versus control subjects (p\&nbsp;\&lt;\&nbsp;0.001 for all). Among cases, every unit increase in capillary density (vessels/mm) was associated with active uveitis (n\&nbsp;=\&nbsp;72 cases) versus inactive disease (n\&nbsp;=\&nbsp;35 cases; odds ratio (OR)\&nbsp;=\&nbsp;1.7; (95\% confidence interval (CI), 1.2-2.5) in multivariate analysis. Furthermore, the presence of any nailfold hemorrhage versus the absence of hemorrhage was more likely to be associated with posterior and panuveitis (n\&nbsp;=\&nbsp;41 cases combined) compared to anterior and intermediate uveitis (n\&nbsp;=\&nbsp;66 cases combined; OR\&nbsp;=\&nbsp;5.8; 95\% CI, 2.3-14.2). Moreover, we found a positive correlation between peripheral retinal leakage and nailfold capillaries dilation (r\&nbsp;=\&nbsp;0.33; p\&nbsp;=\&nbsp;0.015) that was not strictly significant based on the number of comparisons made. CONCLUSIONS: Our study provides support for non-ocular capillary bed abnormalities in uveitis, with interesting correlations based on disease stage and anatomical classification.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2018.1496265},
	author = {Chen, Xuling and Yao, Xuyang and Chi, Ying and Guo, Chunying and Zhang, Jing and Li, Jun and Zhang, Shijie and Rong, Xin and Pasquale, Louis R and Yang, Liu}
}
@article {1522728,
	title = {Glaucoma after Ocular Surgery or Trauma: The Role of Infiltrating Monocytes and Their Response to Cytokine Inhibitors},
	journal = {Am J Pathol},
	volume = {190},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {2056-2066},
	abstract = {Glaucoma is a frequent and devastating long-term complication following ocular trauma, including corneal surgery, open globe injury, chemical burn, and infection. Postevent inflammation and neuroglial remodeling play a key role in subsequent ganglion cell apoptosis and glaucoma. To this end, this study was designed to investigate the amplifying role of monocyte infiltration into the retina. By using three different ocular injury mouse models (corneal suture, penetrating keratoplasty, and globe injury) and monocyte fate mapping techniques, we show that ocular trauma or surgery can cause robust infiltration of bone marrow-derived monocytes into the retina and subsequent neuroinflammation by up-regulation of Tnf, Il1b, and Il6 mRNA within 24 hours. This is accompanied by ganglion cell apoptosis and neurodegeneration. Prompt inhibition of tumor necrosis factor-α or IL-1β markedly suppresses monocyte infiltration and ganglion cell loss. Thus, acute ocular injury (surgical or trauma) can lead to rapid neuroretinal inflammation and subsequent ganglion cell loss, the hallmark of glaucoma. Infiltrating monocytes play a central role in this process, likely amplifying the inflammatory cascade, aiding in the activation of retinal microglia. Prompt administration of cytokine inhibitors after ocular injury prevents this infiltration and ameliorates the damage to the retina-suggesting that it may be used prophylactically for neuroprotection against post-traumatic glaucoma.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.07.006},
	author = {Chen, Xiaoniao and Lei, Fengyang and Zhou, Chengxin and Chodosh, James and Wang, Liqiang and Huang, Yifei and Dohlman, Claes H and Paschalis, Eleftherios I}
}
@article {1328877,
	title = {Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma},
	journal = {Nat Commun},
	volume = {9},
	number = {1},
	year = {2018},
	month = {2018 Aug 10},
	pages = {3209},
	abstract = {Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-05681-9},
	author = {Chen, Huihui and Cho, Kin-Sang and Vu, T H Khanh and Shen, Ching-Hung and Kaur, Mandeep and Chen, Guochun and Mathew, Rose and McHam, M Lisa and Fazelat, Ahad and Lashkari, Kameran and Au, Ngan Pan Bennett and Tse, Joyce Ka Yu and Li, Yingqian and Yu, Honghua and Yang, Lanbo and Stein-Streilein, Joan and Ma, Chi Him Eddie and Woolf, Clifford J and Whary, Mark T and Jager, Martine J and Fox, James G and Chen, Jianzhu and Chen, Dong F}
}
@article {1109781,
	title = {Is Routine Imaging of the Aorta Warranted in Patients With Giant Cell Arteritis?},
	journal = {J Neuroophthalmol},
	year = {2017},
	month = {2017 Jun 13},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000538},
	author = {Chen, John J and Warrington, Kenneth J and Garrity, James A and Prasad, Sashank}
}
@article {1478345,
	title = {Re: Gong et al.: Comparison of United States and international ophthalmic drug pricing (Ophthalmology. 2019;126:1358-1365},
	journal = {Ophthalmology},
	volume = {126},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {e94-e95},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.08.006},
	author = {Chen, Evan and Parikh, Ravi}
}
@article {1363254,
	title = {Altered cholesterol homeostasis in aged macrophages linked to neovascular macular degeneration},
	journal = {Cell Metab},
	volume = {17},
	number = {4},
	year = {2013},
	month = {2013 Apr 02},
	pages = {471-2},
	abstract = {Abnormal lipid metabolism has been linked to age-related macular degeneration (AMD); choroidal neovascularization in late AMD commonly causes blindness. Sene et al. (2013) now demonstrate that in aged macrophages decreased ABCA1 expression, regulated by liver X receptor and miR-33, impairs export of intracellular cholesterol, which promotes neovascular AMD.},
	issn = {1932-7420},
	doi = {10.1016/j.cmet.2013.03.010},
	author = {Chen, Jing and Smith, Lois E H}
}
@article {1517201,
	title = {Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder},
	journal = {Neurology},
	volume = {95},
	number = {2},
	year = {2020},
	month = {2020 Jul 14},
	pages = {e111-e120},
	abstract = {OBJECTIVE: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. METHODS: We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of >=1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for >=6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. RESULTS: Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33\% \&lt;18 years), and 59\% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74\% (14 of 19; ARR 0.67), rituximab 61\% (22 of 36; ARR 0.59), azathioprine 59\% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20\% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5). CONCLUSION: This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.},
	issn = {1526-632X},
	doi = {10.1212/WNL.0000000000009758},
	author = {Chen, John J and Flanagan, Eoin P and Bhatti, M Tariq and Jitprapaikulsan, Jiraporn and Dubey, Divyanshu and Lopez Chiriboga, Alfonso Sebastian S and Fryer, James P and Weinshenker, Brian G and McKeon, Andrew and Tillema, Jan-Mendelt and Lennon, Vanda A and Lucchinetti, Claudia F and Kunchok, Amy and McClelland, Collin M and Lee, Michael S and Bennett, Jeffrey L and Pelak, Victoria S and Van Stavern, Gregory and Adesina, Ore-Ofe O and Eggenberger, Eric R and Acierno, Marie D and Wingerchuk, Dean M and Lam, Byron L and Moss, Heather and Beres, Shannon and Gilbert, Aubrey L and Shah, Veeral and Armstrong, Grayson and Heidary, Gena and Cestari, Dean M and Stiebel-Kalish, Hadas and Pittock, Sean J}
}
@article {1598074,
	title = {Knowledge, attitudes and eye health-seeking behaviours in a population-based sample of people with diabetes in rural China},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {806-811},
	abstract = {AIMS: To assess knowledge of diabetes and acceptance of eye care among people with diabetes in rural China, to improve service uptake. METHODS: Population-based study of people in Guangdong, China, with glycosylated haemoglobin A1c>=6.5\% and/or known history of diabetes. Between August and November 2014, participants answered a questionnaire (based on Delphi process/previous focus groups) on medical history, demographic characteristics, self-rated health and vision, knowledge about diabetes and diabetic retinopathy, quality of local healthcare, barriers to treatment, likely acceptance of eye exams and treatment, and interventions rated most likely to improve service uptake. Presenting visual acuity was assessed, fundus photography performed and images graded by trained graders. Potential predictors of accepting care were evaluated and confounders adjusted for using logistic regression. RESULTS: A total of 562 people (9.6\% (256/5825), mean age 66.2{\textpm}9.84\&nbsp;years, 207 (36.8\%) men) had diabetes, 118 (22.3\%) previously diagnosed. {\textquoteright}Very likely{\textquoteright} or {\textquoteright}likely{\textquoteright} acceptance of laser treatment (140/530=26.4\%) was lower than for eye exams (317/530=59.8\%, p\&lt;0.001). Predictors of accepting both exams and laser included younger age (p\&lt;.001) and prior awareness of diabetes diagnosis (p=0.004 and p=0.035, respectively). The leading barrier to receiving diabetes treatment was unawareness of diagnosis (409/454, 97.2\%), while interventions rated most likely to improve acceptance of eye exams included reimbursement of travel costs (387/562, 73.0\%), video or other health education (359/562, 67.7\%) and phone call reminders (346/562, 65.3\%). CONCLUSIONS: Improving diagnosis of diabetes, along with incentives, education and communication strategies, is most likely to enhance poor acceptance of diabetic eye care in this setting.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316105},
	author = {Chen, Tingting and Jin, Ling and Zhu, Wenhui and Wang, Congyao and Zhang, Guoshan and Wang, Xiuqin and Wang, Jun and Yang, Ke and Cochrane, Gillian M and Lamoureux, Ecosse Luc and Friedman, David S and Gilbert, Suzanne and Lansingh, Van C and Resnikoff, Serge and Zhao, Jialiang and Xiao, Baixiang and He, Mingguang and Congdon, Nathan}
}
@article {1559562,
	title = {Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment},
	journal = {Aging (Albany NY)},
	volume = {12},
	year = {2020},
	month = {2020 Dec 29},
	abstract = {Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL photoreceptors, CD11b macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.},
	issn = {1945-4589},
	doi = {10.18632/aging.202453},
	author = {Chen, XiaoHong and Amorim, Jo{\~a}o A and Moustafa, Giannis A and Lee, Jong-Jer and Yu, Zhen and Ishihara, Kenji and Iesato, Yasuhiro and Barbisan, Paulo and Ueta, Takashi and Togka, Konstantina A and Lu, Lin and Sinclair, David A and Vavvas, Demetrios G}
}
@article {1661815,
	title = {Topical Sustained Delivery of Miltefosine Via Drug-Eluting Contact Lenses to Treat Acanthamoeba Keratitis},
	journal = {Pharmaceutics},
	volume = {14},
	number = {12},
	year = {2022},
	month = {2022 Dec 08},
	abstract = {This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of a methafilcon hydrogel, which was then lathed into a contact lens. During seven days of in vitro testing, all three formulations demonstrated sustained release from the lens at theoretically therapeutic levels. Based on the physicochemical characterization of MLF-CLs, MLF-CL{\textquoteright}s physical properties are not significantly different from commercial contact lenses in terms of light transmittance, water content and wettability. MLF-CLs possessed a slight reduction in compression modulus that was attributed to the inclusion of polymer-drug films but still remain within the optimal range of soft contact lenses. In cytotoxicity studies, MLF-CL indicated up to 91\% viability, which decreased proportionally as miltefosine loading increased. A three-day biocompatibility test on New Zealand White rabbits revealed no impact of MLF-CLs on the corneal tissue. The MLF-CLs provided sustained in vitro release of miltefosine for a week while maintaining comparable physical features to a commercial contact lens. MLF-CL has a promising potential to be used as a successful treatment method for Acanthamoeba keratitis.},
	issn = {1999-4923},
	doi = {10.3390/pharmaceutics14122750},
	author = {Chen, Lin and Kuang, Liangju and Ross, Amy E and Farhat, Wissam and Boychev, Nikolay and Sharfi, Sina and Kanu, Levi N and Liu, Longqian and Kohane, Daniel S and Ciolino, Joseph B}
}
@article {1364591,
	title = {Protective inflammasome activation in AMD},
	journal = {Nat Med},
	volume = {18},
	number = {5},
	year = {2012},
	month = {2012 May 04},
	pages = {658-60},
	abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. AMD progression is associated with alterations in inflammatory pathways and the immune system. A new study identifies a protective role for inflammasomes in AMD, suggesting that inflammasome activation might be manipulated as a potential therapeutic strategy for this condition (pages 791-798).},
	keywords = {Animals, Carrier Proteins, Interleukin-18, Macular Degeneration, NLR Family, Pyrin Domain-Containing 3 Protein, Optic Disk Drusen},
	issn = {1546-170X},
	doi = {10.1038/nm.2761},
	author = {Chen, Jing and Smith, Lois E H}
}
@article {1359920,
	title = {Spectral-Domain OCT: Helping the Clinician Diagnose Glaucoma: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {125},
	number = {11},
	year = {2018},
	month = {2018 Nov},
	pages = {1817-1827},
	abstract = {PURPOSE: To review the current published literature on the use of spectral domain (SD) OCT to help detect changes associated with the diagnosis of glaucoma. METHODS: Searches of the peer-reviewed literature were conducted on June 11, 2014, November 7, 2016, August 8, 2017, and April 19, 2018, in the PubMed and Cochrane Library databases and included only articles published since the last glaucoma imaging Ophthalmic Technology Assessment, which included articles up until February 2006. The abstracts of these 708 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 74 articles were selected, and the panel methodologist (K.N.-M.) assigned ratings to them according to the level of evidence. Two articles were rated level I, 57 articles were rated level II, and the 15 level III articles were excluded. RESULTS: Spectral-domain OCT is capable of detecting damage to the retinal nerve fiber layer (RNFL), macula, and optic nerve in patients with preperimetric and perimetric glaucoma (level I and II evidence). The most commonly studied single parameter was RNFL thickness. Of note, RNFL thickness measurements are not interchangeable between instruments. Various commercially available SD OCT instruments have similar abilities to distinguish patients with known glaucoma from normal subjects. Despite different software protocols, all SD OCT instruments are able to detect the same typical pattern of glaucomatous RNFL loss that affects primarily the inferior, inferior temporal, superior, and superior temporal regions of the optic nerve (level II evidence). Across many SD OCT instruments, macular imaging also can detect a preferential inferior, inferior temporal, and superior temporal thinning in patients with glaucoma compared with controls. Best disc parameters for detecting glaucomatous nerve damage are global rim area, inferior rim area, and vertical cup-to-disc ratio. Studies suggest that newer reference-plane independent optic nerve parameters may have the same or better detection capability when compared with older reference-plane dependent disc parameters (level II evidence). CONCLUSIONS: Structural glaucomatous damage can be detected by SD OCT. Optic nerve, RNFL, and macular parameters can help the clinician distinguish the anatomic changes that are associated with patients with glaucoma when compared with normal subjects.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.05.008},
	author = {Chen, Teresa C and Hoguet, Ambika and Junk, Anna K and Nouri-Mahdavi, Kouros and Radhakrishnan, Sunita and Takusagawa, Hana L and Chen, Philip P}
}
@article {1483615,
	title = {Loss of RAR-related orphan receptor alpha (RORα) selectively lowers docosahexaenoic acid in developing cerebellum},
	journal = {Prostaglandins Leukot Essent Fatty Acids},
	volume = {152},
	year = {2020},
	month = {2020 Jan},
	pages = {102036},
	abstract = {Deficiency in retinoid acid receptor-related orphan receptor alpha (RORα) of staggerer mice results in extensive granule and Purkinje cell loss in the cerebellum as well as in learned motor deficits, cognition impairments and perseverative tendencies that are commonly observed in autistic spectrum disorder (ASD). The effects of RORα on brain lipid metabolism associated with cerebellar atrophy remain unexplored. The aim of this study is to examine the effects of RORα deficiency on brain phospholipid fatty acid concentrations and compositions. Staggerer mice (Rora) and wildtype littermates (Rora) were fed n-3 polyunsaturated fatty acids (PUFA) containing diets ad libitum. At 2 months and 7 or more months old, brain total phospholipid fatty acids were quantified by gas chromatography-flame ionization detection. In the cerebellum, all fatty acid concentrations were reduced in 2 months old mice. Since total fatty acid concentrations were significantly different at 2-month-old, we examined changes in fatty acid composition. The composition of ARA was not significantly different between genotypes; though DHA composition remained significantly lowered. Despite cerebellar atrophy at \&gt;7-months-old, cerebellar fatty acid concentrations had recovered comparably to wildtype control. Therefore, RORα may be necessary for fatty acid accretions during neurodevelopment. Specifically, the effects of RORα on PUFA metabolisms are region-specific and age-dependent.},
	issn = {1532-2823},
	doi = {10.1016/j.plefa.2019.102036},
	author = {Chen, Chuck T and Schultz, Joseph A and Haven, Sophie E and Wilhite, Breanne and Liu, Chi-Hsiu and Chen, Jing and Hibbeln, Joseph R}
}
@article {1319462,
	title = {Trends in dacryocystitis in China: A STROBE-compliant article},
	journal = {Medicine (Baltimore)},
	volume = {97},
	number = {26},
	year = {2018},
	month = {2018 Jun},
	pages = {e11318},
	abstract = {The aim of the study was to review the distribution, current trends, and microbiological characteristics of bacterial pathogens isolated from dacryocystitis patients in China during the last 15 years.This is a retrospective multiple-center noncomparative case series. The medical records of 15,452 consecutive patients from 7 cities diagnosed as having dacryocystitis between 2002 and 2016 were reviewed. The patients{\textquoteright} demographics, microbiological data, and antibiotic sensitivity were reviewed and analyzed.A total of 3344 lacrimal sac content cultures were taken (21.6\%) during the study period. A pathogen was identified in 1996 samples (59.7\%), with bacterial isolates accounting for 1902 of the positive cultures (95.3\%). Gram-positive isolates, gram-negative isolates, and anaerobic bacteria were found in 1218 (61.0\%), 607 (30.4\%), and 285 (14.3\%) samples, respectively. An increase in gram-positive isolates over the study duration was found (P = .003). The predominant isolates were coagulase negative Staphylococci (485, 25.5\%), Staphylococcus aureus (186, 9.8\%), Pseudomonas aeruginosa (184, 9.7\%), and Haemophilus influenzae (152, 9.0\%). There was a trend toward increasing resistance to erythromycin from 10.5\% during the first 5 years of the study to 20.7\% during the last 5 years (P \&lt; .001). Antimicrobial susceptibility testing showed that gatifloxacin was the most effective drug against most of gram-positive, gram-negative, and anaerobic bacteria.The microbial culture rate of dacryocystitis in China is low. There was an increase in the percentage of gram-positive bacteria over time. The sensitivity of gram-positive isolates to tested antibiotics is relatively low compared with that of gram-negative isolates. Our data show that the empiric use of fourth-generation fluoroquinolones in refractory dacryocystitis may be justified.},
	issn = {1536-5964},
	doi = {10.1097/MD.0000000000011318},
	author = {Chen, Lijuan and Fu, Tongsheng and Gu, Hao and Jie, Ying and Sun, Zhongmou and Jiang, Donghong and Yu, Jibing and Zhu, Xinxing and Xu, Jianjiang and Hong, Jiaxu}
}
@article {1522713,
	title = {Association of the Affordable Care Act Medicaid Expansion with Dilated Eye Examinations among the United States Population with Diabetes},
	journal = {Ophthalmology},
	volume = {127},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {920-928},
	abstract = {PURPOSE: To evaluate the association between Medicaid expansion and diabetic dilated eye examinations. DESIGN: A retrospective difference in differences (DiD) analysis using individual-level survey response data from January 1, 2009, to December 31,\&nbsp;2017. PARTICIPANTS: A total of 52 392 survey responses from 50 states and the District of Columbia between 2009 and 2017. Responders were adults aged 18 to 64 years reporting a previous diagnosis of diabetes and a household income below 138\% of the US federal poverty line (FPL). METHODS: The Centers for Disease Control and Prevention{\textquoteright}s Behavioral Risk Factor Surveillance System data were used to identify survey responders who were asked about the presence of dilated eye examinations from years before and after Medicaid expansion implementation. MAIN OUTCOME MEASURES: The DiD in proportion of dilated eye examinations among diabetic persons aged 18 to 64 years with household incomes below 138\% of the FPL between states that did and did not implement Medicaid expansion. RESULTS: Implementation of Medicaid expansion policies was associated with a 1.3\% (95\% confidence interval [CI],\&nbsp;-3.8 to 6.4; P\&nbsp;= 0.61), 6.3\% (95\% CI, 1.3-11.3; P\&nbsp;= 0.016), 4.1\% (95\% CI,\&nbsp;-0.8 to 9.0; P\&nbsp;= 0.11), and 2.3\% (95\% CI,\&nbsp;-1.6 to 6.2; P\&nbsp;= 0.23) increase in the proportion of diabetic persons aged 18 to 64 years with incomes below 138\% of the FPL receiving a dilated eye examination within the past year due to Medicaid expansion 1, 2, 3, and 4 cumulative years after expansion, respectively. CONCLUSIONS: Medicaid expansion policies were significantly associated with an increase in dilated eye examination rates within the first 2 years after implementation. However, this increase did not persist beyond this period, with nonsignificant increases 3 and 4 cumulative years after implementation. Healthcare policymakers should be aware that additional measures beyond expanding insurance coverage may be necessary to increase and sustain the rate of dilated eye examinations among diabetic populations.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.09.010},
	author = {Chen, Evan M and Armstrong, Grayson W and Cox, Jacob T and Wu, David M and Hoover, Donald R and Del Priore, Lucian V and Parikh, Ravi}
}
@article {1417551,
	title = {Polybenzyl Glutamate Biocompatible Scaffold Promotes the Efficiency of Retinal Differentiation toward Retinal Ganglion Cell Lineage from Human-Induced Pluripotent Stem Cells},
	journal = {Int J Mol Sci},
	volume = {20},
	number = {1},
	year = {2019},
	month = {2019 Jan 05},
	abstract = {Optic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.},
	issn = {1422-0067},
	doi = {10.3390/ijms20010178},
	author = {Chen, Ta-Ching and She, Pin-Yi and Chen, Dong Feng and Lu, Jui-Hsien and Yang, Chang-Hao and Huang, Ding-Siang and Chen, Pao-Yang and Lu, Chen-Yu and Cho, Kin-Sang and Chen, Hsin-Fu and Su, Wei-Fang}
}
@article {1302172,
	title = {Impact of aromatase absence on murine intraocular pressure and retinal ganglion cells},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Feb 19},
	pages = {3280},
	abstract = {We hypothesize that aromatase, an enzyme that regulates estrogen production, plays a significant role in the control of intraocular pressure (IOP) and retinal ganglion cells (RGCs). To begin to test our hypothesis, we examined the impact of aromatase absence, which completely eliminates estrogen synthesis, in male and female mice. Studies were performed with adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice. IOP was measured in a masked fashion in both eyes of conscious mice at 12 and 24 weeks of age. Retinas were obtained and processed for RGC counting with a confocal microscope. IOP levels in both 12- and 24-week old female ArKO mice were significantly higher than those of age- and sex-matched WT controls. The mean increase in IOP was 7.9\% in the 12-week-, and 19.7\% in the 24-week-old mice, respectively. These changes were accompanied by significant 9\% and 7\% decreases in RGC numbers in the ArKO female mice, relative to controls, at 12- and 24-weeks, respectively. In contrast, aromatase deficiency did not lead to an increased IOP in male mice. There was a significant reduction in RGC counts in the 12-, but not 24-, week-old male ArKO mice, as compared to their age- and sex-matched WT controls. Overall, our findings show that aromatase inhibition in females is associated with elevated IOP and reduced RGC counts.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-21475-x},
	author = {Chen, Xiaomin and Liu, Yang and Zhang, Yi and Kam, Wendy R and Pasquale, Louis R and Sullivan, David A}
}
@article {1504056,
	title = {The functions of IL-23 and IL-2 on driving autoimmune effector T-helper 17 cells into the memory pool in dry eye disease},
	journal = {Mucosal Immunol},
	volume = {14},
	number = {1},
	year = {2021},
	month = {2021 01},
	pages = {177-186},
	abstract = {Long-lived memory T-helper 17 (Th17) cells actively mediate the chronic inflammation in autoimmune disorders, including dry eye disease (DED). The mechanisms responsible for the maintenance and reactivation of these cells in autoimmunity have been subject of investigation. However, the process through which memory Th17 are generated from their effector precursors remains to be elucidated. Herein, using our murine model of DED, we detect a linear transition from effector-to-memory Th17 cells during the abatement phase of acute inflammation, which is accompanied by persistently high levels of IL-23 and diminished levels of IL-2. In addition, in vitro culture of effector Th17 cells derived from the DED animals with IL-23, but not IL-2, leads to significant generation of memory Th17 cells, along with upregulated expression levels of IL-7R and IL-15R by these cells. Furthermore, supplementation of IL-2 abolishes and blockade of IL-2 enhances IL-23-induced generation of memory Th17 cells in vitro. Finally, in vivo blockade of IL-23 signaling during the contraction phase of primary response inhibits the generation of memory Th17 cells from their effector precursors. Together, our data demonstrate a new dichotomy between IL-23 and IL-2 in driving effector Th17 cells into the memory pool in autoimmune-mediated ocular surface inflammation.},
	issn = {1935-3456},
	doi = {10.1038/s41385-020-0289-3},
	author = {Chen, Yihe and Shao, Chunyi and Fan, Nai-Wen and Nakao, Takeshi and Amouzegar, Afsaneh and Chauhan, Sunil K and Dana, Reza}
}
@article {742241,
	title = {Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma.},
	journal = {PLoS One},
	volume = {11},
	number = {6},
	year = {2016},
	month = {2016},
	pages = {e0157093},
	abstract = {Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P \&gt; 0.07) or with PAC/PACG subgroups (Pc \&gt; 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P \&lt; 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P \&gt; 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0157093},
	author = {Chen, Xueli and Chen, Yuhong and Wiggs, Janey L and Pasquale, Louis R and Sun, Xinghuai and Fan, Bao Jian}
}
@article {1109786,
	title = {IFN-γ-Expressing Th17 Cells Are Required for Development of Severe Ocular Surface Autoimmunity},
	journal = {J Immunol},
	volume = {199},
	number = {3},
	year = {2017},
	month = {2017 Aug 01},
	pages = {1163-1169},
	abstract = {Th17 cells are critical effectors mediating the ocular surface autoimmunity in dry eye disease (DED). Increased IFN-γ has also been implicated in DED; however, it remains unclear to what extent Th1 cells contribute to DED pathogenesis. In this study, we investigated the cellular source of IFN-γ and assessed its contribution to corneal epitheliopathy in DED mice. We discovered a significant IL-17A(+)IFN-γ(+) (Th17/1) population and determined that these cells are derived from Th17 precursors. Adoptive transfer of Th17/1, but not Th1, cells confers the disease to naive recipients as effectively as do Th17 cells alone. DED-induced IL-12 and IL-23 are required for in vivo transition of pathogenic Th17 cells to IFN-γ producers. Furthermore, using IFN-γ-deficient Th17 cells, we demonstrate the disease-amplifying role of Th17-derived IFN-γ in DED pathogenesis. These results clearly demonstrate that Th17 cells mediate ocular surface autoimmunity through both IL-17A and IFN-γ.},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1602144},
	author = {Chen, Yihe and Chauhan, Sunil K and Shao, Chunyi and Omoto, Masahiro and Inomata, Takenori and Dana, Reza}
}
@article {1732556,
	title = {The Role of Gut Microbiota in Glaucoma Progression and Other Retinal Diseases},
	journal = {Am J Pathol},
	volume = {193},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1662-1668},
	abstract = {As a rapidly growing field, microbiota research offers novel approaches to promoting ocular health and treating major retinal diseases, such as glaucoma. Gut microbiota changes throughout life; however, certain patterns of population changes have been increasingly associated with specific diseases. It has been well established that a disrupted microbiome contributes to central nervous system diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, and glioma, suggesting a prominent role of microbiome in neurodegenerative diseases. This review summarizes the progress in identifying significant changes in the microbial composition of patients with glaucoma by compiling studies on the association between microbiota and disease progression. Of interest is the relationship between increased Firmicutes/Bacteroidetes ratio in patients with primary open-angle glaucoma, increased taurocholic acid, decreased glutathione, and a reduction in retinal ganglion cell survival. Connecting these microbes to specific metabolites sheds light on the pathogenic mechanism and novel treatment strategies. In summary, the current review synthesizes the findings of several studies investigating the effects of shifting bacterial population in retinal diseases, particularly glaucoma, with the aim to identify the current direction of treatment and help direct future endeavors.},
	keywords = {Gastrointestinal Microbiome, Glaucoma, Glaucoma, Open-Angle, Humans, Retinal Diseases, Retinal Ganglion Cells},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2023.06.015},
	author = {Chen, Julie and Chen, Dong Feng and Cho, Kin-Sang}
}
@article {1351145,
	title = {Proton beam irradiation for non-AMD CNV: 2-year results of a randomised clinical trial},
	journal = {Br J Ophthalmol},
	volume = {98},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1212-7},
	abstract = {AIMS: To evaluate safety and visual outcomes after proton beam irradiation (PBI) therapy for subfoveal choroidal neovascularisation (CNV) secondary to causes other than age-related macular degeneration (AMD). METHODS: This study is a prospective, unmasked and randomised clinical trial using two dosage regimens, conducted in the Massachusetts Eye and Ear Infirmary. The study included 46 patients with CNV secondary to non-AMD and best-corrected visual acuity of 20/320 or better. Patients were randomly assigned to receive 16 or 24 cobalt gray equivalents (CGE) of PBI in two equal fractions. Complete ophthalmological examinations, fundus photography and fluorescein angiography were performed at baseline and 6, 12, 18 and 24 months after treatment. RESULTS: At 1 year after treatment, 82\% and 72\% lost fewer than 1.5 lines of vision in the 16 CGE and in 24 CGE groups, respectively. At 2 years after therapy, 77\% in the lower dose group and 64\% in the higher dose group lost fewer than 1.5 lines of vision. Mild radiation complications such as radiation vasculopathy developed in 17.6\% of patients. CONCLUSIONS: PBI is a safe and efficacious treatment for subfoveal CNV not due to AMD. The data with respect to visual outcomes and radiation complications trend in favour of the 16 CGE group, although differences do not reach statistical significance. PBI may be considered as an alternative to current therapies.},
	keywords = {Adolescent, Adult, Aged, Choroidal Neovascularization, Dose-Response Relationship, Radiation, Female, Humans, Male, Middle Aged, Patient Selection, Prospective Studies, Protons, Radiation Injuries, Radiotherapy Dosage, Retinal Diseases, Treatment Outcome, Visual Acuity, Young Adult},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2013-304761},
	author = {Chen, Ling and Kim, Ivana K and Lane, Anne M and Gauthier, Danny and Munzenrider, John E and Gragoudas, Evangelos S and Miller, Joan W}
}
@article {1511483,
	title = {Ocular Manifestations of Chordin-like 1 Knockout Mice},
	journal = {Cornea},
	volume = {39},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {1145-1150},
	abstract = {PURPOSE: In humans, loss-of-function mutations in the gene encoding Chordin-like 1 (CHRDL1) cause X-linked megalocornea (MGC1), characterized by bilateral corneal enlargement, decreased corneal thickness, and increased anterior chamber depth (ACD). We sought to determine whether Chrdl1 knockout (KO) mice would recapitulate the ocular findings found in patients with MGC1. METHODS: We generated mice with a Chrdl1 KO allele and confirmed that male Chrdl1 hemizygous KO mice do not express Chrdl1 mRNA. We examined the eyes of male mice that were hemizygous for either the wild-type (WT) or KO allele and measured corneal diameter, corneal area, corneal thickness, endothelial cell density, ACD, tear volume, and intraocular pressure. We also harvested retinas and counted retinal ganglion cell numbers. Eye segregation pattern in the dorsal lateral geniculate nucleus were also compared between male Chrdl1 KO and WT mice. RESULTS: Male Chrdl1 KO mice do not have larger cornea diameters than WT mice. KO mice have significantly thicker central corneas (116.5 {\textpm} 3.9 vs. 100.9 {\textpm} 4.2 μm, P = 0.013) and smaller ACD (325.7 {\textpm} 5.7 vs. 405.6 {\textpm} 6.3 μm, P \&lt; 0.001) than WT mice, which is the converse of what occurs in patients who lack CHRDL1. Retinal-thalamic projections and other ocular measurements did not significantly differ between KO and WT mice. CONCLUSIONS: Male Chrdl1 KO mice do not have the same anterior chamber abnormalities seen in humans with CHRDL1 mutations. Therefore, Chrdl1 KO mice do not recapitulate the human MGC1 phenotype. Nevertheless, Chrdl1 plays a role during mouse ocular development because corneas in KO mice differ from those in WT mice.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002371},
	author = {Chen, Di and Liu, Yang and Shu, Guanhua and Chinfei Chen and Sullivan, David A and Kam, Wendy R and Hann, Steven and Fowler, Megan and Warman, Matthew L}
}
@article {1452968,
	title = {Inactive Cas9 blocks vitreous-induced expression of Mdm2 and proliferation and survival of retinal pigment epithelial cells},
	journal = {Exp Eye Res},
	volume = {186},
	year = {2019},
	month = {2019 Sep},
	pages = {107716},
	abstract = {Mouse double minute (MDM)2 single nucleotide polymorphism (SNP) 309G allele in the second promoter of MDM2 enhances vitreous-induced expression of Mdm2 and degradation of the tumor suppressor protein p53. This MDM2 contributes to certain cancer development and experimental proliferative vitreoretinopathy. The goal of this study is to discover a novel strategy to only block vitreous-induced expression of Mdm2 for preventing vitreous-induced cell proliferation and survival and thus find a potential novel strategy to treat proliferation-related diseases. We created two mutations (D10A and H840A) in Streptococcus pyogenes (Sp)Cas9 within the nuclease domains (RuvC1 and HNH, respectively) to render this SpCas9 nuclease dead named as dCas9 in a lentiCRISPR v2 vector. Then an MDM2-sgRNA targeting the second promoter of human MDM2 gene was cloned into this vector for producing lentivirus to infect human retinal pigment epithelial (RPE) cells with, which carry a heterozygous genotype of MDM2. lacZ-sgRNA was used as a control. As a result, we discovered that vitreous from experimental rabbits induced a 1.9 {\textpm} 0.2 fold increase in Mdm2 and a 2.0 {\textpm} 0.2 fold decrease in p53 in the RPE cells with dCas9/lacZ-sgRNA compared to those with dCas9/MDM2-sgRNA, suggesting that dCas9 under the guidance of the MDM2-sgRNA prevented RV-stimulated increase in Mdm2. In addition, we found that the rabbit vitreous significantly enhanced cell proliferation (1.5 {\textpm} 0.2 fold), survival against apoptosis (2.2 {\textpm} 0.2 fold), migration (10 {\textpm} 1.5\%) and contraction (112.7 {\textpm} 14.1 mm) of the cells with dCas9/lacZ-sgRNA compared with those with dCas9/MDM2-sgRNA. These results indicated that application of the dCas9 targeted to the P2 of MDM2 is a potential therapeutic approach to diseases due to the P2-driven aberrant expression of Mdm2 - such as proliferative vitreoretinopathy.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.107716},
	author = {Chen, Na and Hu, Zhengping and Yang, Yanhui and Han, Haote and Lei, Hetian}
}
@article {1318855,
	title = {Influence of lipopolysaccharide on proinflammatory gene expression in human corneal, conjunctival and meibomian gland epithelial cells},
	journal = {Ocul Surf},
	volume = {16},
	number = {3},
	year = {2018},
	month = {2018 Jul},
	pages = {382-389},
	abstract = {PURPOSE: Lipopolysaccharide (LPS), a bacterial endotoxin, is known to stimulate leuokotriene B4 (LTB4) secretion by human corneal (HCECs), conjunctival (HConjECs) and meibomian gland (HMGECs) epithelial cells. We hypothesize that this LTB4 effect represents an overall induction of proinflammatory gene expression in these cells. Our objective was to test this hypothesis. METHODS: Immortalized HCECs, HConjECs and HMGECs were cultured in the presence or absence of LPS (15 μg/ml) and ligand binding protein (LBP; 150 ng/ml). Cells were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and GeneSifter software. RESULTS: Our findings show that LPS induces a striking increase in proinflammatory gene expression in HCECs and HConjECs. These cellular reactions are associated with a significant up-regulation of genes associated with inflammatory and immune responses (e.g. IL-1β, IL-8, and tumor necrosis factor), including those related to chemokine and Toll-like receptor signaling pathways, cytokine-cytokine receptor interactions, and chemotaxis. In contrast, with the exception of Toll-like signaling and associated innate immunity pathways, almost no proinflammatory ontologies were upregulated by LPS in HMGECs. CONCLUSIONS: Our results support our hypothesis that LPS stimulates proinflammatory gene expression in HCECs and HConjECs. However, our findings also show that LPS does not elicit such proinflammatory responses in HMGECs.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.05.003},
	author = {Chen, Di and Sahin, Afsun and Kam, Wendy R and Liu, Yang and Rahimi Darabad, Raheleh and Sullivan, David A}
}
@article {1363255,
	title = {Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {4},
	year = {2013},
	month = {2013 Apr 03},
	pages = {2457-64},
	abstract = {PURPOSE: A majority of experimental data on dry eye disease (DED) immunopathogenesis have been derived from a murine model of DED that combines desiccating environmental stress with systemic muscarinic acetylcholine receptor (mAChR) inhibition. However, to our knowledge the effects of pharmacologic mAChR blockade on the pathogenesis of experimental DED have not been evaluated systemically. The purpose of our study was to investigate the differential effects of desiccating environmental stress and mAChR inhibition on the pathogenesis of DED. METHODS: DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled-environment chamber or to systemic scopolamine, or by performing extraorbital lacrimal gland excision. Clinical disease was assessed using corneal fluorescein staining (CFS) and the cotton thread test (CTT). Corneal CD11b(+) and conjunctival CD3(+) T-cell infiltration were evaluated by flow cytometry. T-cells from draining cervical lymph nodes (CLN) and distant inguinal lymph nodes (ILN) were analyzed for Th1, Th2, Th17, and Treg responses by flow cytometry and ELISA. RESULTS: Desiccating environmental stress and systemic mAChR blockade induced similar clinical signs of DED. However, desiccating environmental stress imparted higher conjunctival CD3(+) T-cell infiltration, and greater Th17-cell activity and Treg dysfunction than mAChR blockade, while mAChR blockade decreased tear secretion to a greater extent than desiccating environmental stress. Systemic mAChR blockade attenuated Th17 activity and enhanced Th2 and Treg responses without affecting Th1 activity. CONCLUSIONS: In vivo inhibition of mAChRs variably affects CD4(+) T-cell subsets, and desiccating environmental stress and systemic mAChR blockade induce DED through different primary pathogenic mechanisms.},
	keywords = {Animals, Cytokines, Disease Models, Animal, Dry Eye Syndromes, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Lacrimal Apparatus, Lymph Nodes, Mice, Mice, Inbred C57BL, Muscarinic Antagonists, Receptors, Muscarinic, Scopolamine Hydrobromide, Stress, Physiological, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Th1 Cells, Th17 Cells, Th2 Cells},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-11121},
	author = {Chen, Yihe and Chauhan, Sunil K and Lee, Hyun Soo and Stevenson, William and Schaumburg, Chris S and Sadrai, Zahra and Saban, Daniel R and Kodati, Shilpa and Stern, Michael E and Dana, Reza}
}
@article {416836,
	title = {The Effect of Phacoemulsification on Intraocular Pressure in Glaucoma Patients: A Report by the American Academy of Ophthalmology.},
	journal = {Ophthalmology},
	volume = {122},
	number = {7},
	year = {2015},
	month = {2015 Jul},
	pages = {1294-307},
	abstract = {OBJECTIVE: To examine effects of phacoemulsification on longer-term intraocular pressure (IOP) in patients with medically treated primary open-angle glaucoma (POAG; including normal-tension glaucoma), pseudoexfoliation glaucoma (PXG), or primary angle-closure glaucoma (PACG), without prior or concurrent incisional glaucoma surgery. METHODS: PubMed and Cochrane database searches, last conducted in December 2014, yielded 541 unique citations. Panel members reviewed titles and abstracts and selected 86 for further review. The panel reviewed these articles and identified 32 studies meeting the inclusion criteria, for which the panel methodologist assigned a level of evidence based on standardized grading adopted by the American Academy of Ophthalmology. One, 15, and 16 studies were rated as providing level I, II, and III evidence, respectively. RESULTS: All follow-up, IOP, and medication data listed are weighted means. In general, the studies reported on patients using few glaucoma medications (1.5-1.9 before surgery among the different diagnoses). For POAG, 9 studies (total, 461 patients; follow-up, 17 months) showed that phacoemulsification reduced IOP by 13\% and glaucoma medications by 12\%. For PXG, 5 studies (total, 132 patients; follow-up, 34 months) showed phacoemulsification reduced IOP by 20\% and glaucoma medications by 35\%. For chronic PACG, 12 studies (total, 495 patients; follow-up, 16 months) showed phacoemulsification reduced IOP by 30\% and glaucoma medications by 58\%. Patients with acute PACG (4 studies; total, 119 patients; follow-up, 24 months) had a 71\% reduction from presenting IOP and rarely required long-term glaucoma medications when phacoemulsification was performed soon after medical reduction of IOP. Trabeculectomy after phacoemulsification was uncommon; the median rate reported within 6 to 24 months of follow-up in patients with controlled POAG, PXG, or PACG was 0\% and was 7\% in patients with uncontrolled chronic PACG. CONCLUSIONS: Phacoemulsification typically results in small, moderate, and marked reductions of IOP and medications for patients with POAG, PXG, and PACG, respectively, and using 1 to 2 medications before surgery. Trabeculectomy within 6 to 24 months after phacoemulsification is rare in such patients. However, reports on its effects in eyes with advanced disease or poor IOP control before surgery are few, particularly for POAG and PXG.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.03.021},
	author = {Chen, Philip P and Lin, Shan C and Junk, Anna K and Radhakrishnan, Sunita and Singh, Kuldev and Chen, Teresa C}
}
@article {1635627,
	title = {Immune regulation of the ocular surface},
	journal = {Exp Eye Res},
	volume = {218},
	year = {2022},
	month = {2022 05},
	pages = {109007},
	abstract = {Despite constant exposure to various environmental stimuli, the ocular surface remains intact and uninflamed while maintaining the transparency of the cornea and its visual function. This {\textquoteright}immune privilege{\textquoteright} of the ocular surface is not simply a result of the physical barrier function of the mucosal lining but, more importantly, is actively maintained through a variety of immunoregulatory mechanisms that prevent the disruption of immune homeostasis. In this review, we focus on essential molecular and cellular players that promote immune quiescence in steady-state conditions and suppress inflammation in disease-states. Specifically, we examine the interactions between the ocular surface and its local draining lymphoid compartment, by encompassing the corneal epithelium, corneal nerves and cornea-resident myeloid cells, conjunctival goblet cells, and regulatory T cells (Treg) in the context of ocular surface autoimmune inflammation (dry eye disease) and alloimmunity (corneal transplantation). A better understanding of the immunoregulatory mechanisms will facilitate the development of novel, targeted immunomodulatory strategies for a broad range of ocular surface inflammatory disorders.},
	keywords = {Conjunctiva, Cornea, Corneal Transplantation, Dry Eye Syndromes, Humans, Inflammation},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2022.109007},
	author = {Chen, Yihe and Wang, Shudan and Alemi, Hamid and Dohlman, Thomas and Dana, Reza}
}
@article {1364592,
	title = {Propranolol inhibition of β-adrenergic receptor does not suppress pathologic neovascularization in oxygen-induced retinopathy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {6},
	year = {2012},
	month = {2012 May 17},
	pages = {2968-77},
	abstract = {PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of blindness in children and is, in its most severe form, characterized by uncontrolled growth of vision-threatening pathologic vessels. Propranolol, a nonselective β-adrenergic receptor blocker, was reported to protect against pathologic retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Based on this single animal study using nonstandard evaluation of retinopathy, clinical trials are currently ongoing to evaluate propranolol treatment in stage 2 ROP patients who tend to experience spontaneous disease regression and are at low risk of blindness. Because these ROP patients are vulnerable premature infants who are still in a fragile state of incomplete development, the efficacy of propranolol treatment in retinopathy needs to be evaluated thoroughly in preclinical animal models of retinopathy and potential benefits weighed against potential adverse effects. METHODS: Retinopathy was induced by exposing neonatal mice to 75\% oxygen from postnatal day (P) 7 to P12. Three routes of propranolol treatment were assessed from P12 to P16: oral gavage, intraperitoneal injection, or subcutaneous injection, with doses varying between 2 and 60 mg/kg/day. At P17, retinal flatmounts were stained with isolectin and quantified with a standard protocol to measure vasoobliteration and pathologic neovascularization. Retinal gene expression was analyzed with qRT-PCR using RNA isolated from retinas of control and propranolol-treated pups. RESULTS: None of the treatment approaches at any dose of propranolol (up to 60 mg/kg/day) were effective in preventing the development of retinopathy in a mouse model of OIR, evaluated using standard techniques. Propranolol treatment also did not change retinal expression of angiogenic factors including vascular endothelial growth factor. CONCLUSIONS: Propranolol treatment via three routes and up to 30 times the standard human dose failed to suppress retinopathy development in mice. These data bring into question whether propranolol through inhibition of β-adrenergic receptors is an appropriate therapeutic approach for treating ROP.},
	keywords = {Administration, Oral, Adrenergic beta-Antagonists, Angiopoietin-1, Angiopoietin-2, Animals, Animals, Newborn, Cell Proliferation, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Endothelial Cells, Enzyme-Linked Immunosorbent Assay, Erythropoietin, Gene Expression Profiling, Humans, In Vitro Techniques, Infant, Newborn, Injections, Intraperitoneal, Injections, Subcutaneous, Mice, Oxygen, Propranolol, Receptors, Adrenergic, beta, Receptors, Vascular Endothelial Growth Factor, Retina, Retinal Neovascularization, Retinopathy of Prematurity, Reverse Transcriptase Polymerase Chain Reaction, RNA, Up-Regulation, Vascular Endothelial Growth Factor A},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-9691},
	author = {Chen, Jing and Joyal, Jean-Sebastian and Hatton, Colman J and Juan, Aimee M and Pei, Dorothy T and Hurst, Christian G and Xu, Dan and Stahl, Andreas and Hellstrom, Ann and Smith, Lois E H}
}
@article {705046,
	title = {Molecular Identification and Epidemiological Features of Human Adenoviruses Associated with Acute Respiratory Infections in Hospitalized Children in Southern China, 2012-2013.},
	journal = {PLoS One},
	volume = {11},
	number = {5},
	year = {2016},
	month = {2016},
	pages = {e0155412},
	abstract = {BACKGROUND: Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. METHODS: Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs) of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed. RESULTS: Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and HAdV were 13.7\%, 13.2\%, and 12.0\%, respectively. The HAdV positive patients accounted for 7.9\%, 17.2\%, 17.5\% and 10.7\% in age groups \&lt;1, 1-3, 3-6 and 6-14 years, respectively. Eighty-four HAdV positive children were co-infected with other respiratory pathogens (84/495, 17.0\%). The most common co-infection pathogens with HAdV were MP (57.1\%) and Human Bocavirus (HBoV) (16.7\%). The majority of HAdV infected patients were totally recovered (96.9\%, 480/495); However, four (0.8\%) patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70\%), followed by HAdV-7 (28\%). These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the first time in Guangzhou metropolitan area. Phylogenetic analysis indicated that all the HVR sequences of the hexon gene of HAdV-3 and -7 strains have high similarity within their individual types, and these strains were also similar to those circulating in China currently, indicating the conservation of hexon genes of both HAdV-3 and HAdV-7. CONCLUSIONS: Knowledge of the epidemiological features and molecular types of HAdV, a major pathogen of pediatric ARI, as well as other co-infected respiratory pathogens circulating in Guangzhou, southern China, is vital to predict and prevent future disease outbreaks in children. This study will certainly facilitate HAdV vaccine development and treatment of HAdV infections in children.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0155412},
	author = {Chen, Yi and Liu, Fanghua and Wang, Changbing and Zhao, Mingqi and Deng, Li and Zhong, Jiayu and Zhang, Yingying and Ye, Jun and Jing, Shuping and Cheng, Zetao and Guan, Yongxin and Ma, Yi and Sun, Yuanyuan and Zhu, Bing and Zhang, Qiwei}
}
@article {560256,
	title = {Pseudomonas Aeruginosa: A Masquerader in Sino-Orbital Infections.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {5},
	year = {2016},
	month = {2016 Sep-Oct},
	pages = {374-7},
	abstract = {PURPOSE: To report 2 immunocompromised patients with sino-orbital necrotizing pseudomonas infections and review the literature. METHODS: This is a noncomparative, retrospective case series, and review. The clinical data of 2 patients with histopathologic and microbiologic diagnoses of pseudomonas sinus infections causing orbital cellulitis were obtained from medical records. A retrospective literature review was performed on all reported cases of periorbital pseudomonas infections. RESULTS: One patient with acquired immune deficiency syndrome was noted to have orbital cellulitis with clear visualization of eschar in the middle turbinate on nasal endoscopy. A second patient also had orbital cellulitis with ophthalmoplegia and presence of eschar in the sinus. Both patients had some degree of erosion through the lamina papyracea found on orbital imaging and both had intact vision without optic neuropathy. Pseudomonas infection was confirmed in both cases with permanent histopathology and cultures from conservative sinus debridement. CONCLUSIONS: Pseudomonas sino-orbital infections must be considered in the differential diagnosis in cases of eschar and orbital wall erosion especially when vision is preserved in immunocompromised individuals. This finding obviates the need for radical debridement including orbital exenteration, which can be indicated in cases of invasive fungal disease.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000558},
	author = {Chen, Xi and Bleier, Benjamin S and Lefebvre, Daniel R and Lee, Nahyoung Grace}
}
@article {1333848,
	title = {Author Correction: Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma},
	journal = {Nat Commun},
	volume = {9},
	number = {1},
	year = {2018},
	month = {2018 Sep 20},
	pages = {3914},
	abstract = {The originally published version of this Article contained an error in Figure 4. The bar chart in panel f was inadvertently replaced with a duplicate of the bar chart in panel e. This error has now corrected in both the PDF and HTML versions of the Article.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-06428-2},
	author = {Chen, Huihui and Cho, Kin-Sang and Vu, T H Khanh and Shen, Ching-Hung and Kaur, Mandeep and Chen, Guochun and Mathew, Rose and McHam, M Lisa and Fazelat, Ahad and Lashkari, Kameran and Au, Ngan Pan Bennett and Tse, Joyce Ka Yu and Li, Yingqian and Yu, Honghua and Yang, Lanbo and Stein-Streilein, Joan and Ma, Chi Him Eddie and Woolf, Clifford J and Whary, Mark T and Jager, Martine J and Fox, James G and Chen, Jianzhu and Chen, Dong F}
}
@article {1517209,
	title = {A Patient With Glaucoma With Corneal Edema},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Jun 25},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.1023},
	author = {Chen, Teresa C and Jurkunas, Ula and Chodosh, James}
}
@article {416991,
	title = {Melkersson-rosenthal syndrome with isolated unilateral eyelid edema: an immunopathologic study.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {3},
	year = {2015},
	month = {2015 May-Jun},
	pages = {e70-7},
	abstract = {Lymphedema is caused by defective drainage of the lymphatic system. In Melkersson-Rosenthal syndrome, involvement is predominantly of the lumens with blockage of lymphatic channels by histiocytic-epithelioid cell clusters accompanied by dermal granulomas and lymphocytes. It is a localized, painless, nonitching, and nonpitting form of lymphedema. Besides the eyelids, the disease can cause lip edema, facial palsy, and/or fissured tongue. It is rare and has received little attention in the ophthalmic literature, either in its complete triadic form, or more frequently, in its monosymptomatic forms. Pathogenesis is not well understood, and there is no effective therapy. The authors describe a case of Melkesson-Rosenthal syndrome in a 45-year-old Hispanic man with isolated unilateral upper eyelid edema. Histopathological and immunohistochemical evaluations of an eyelid biopsy specimen revealed intravascular and extravascular clusters of histiocytic-epithelioid cells that were CD68/163-positive. Variable numbers of mostly T-lymphocytes were found in the epidermis, dermis, and orbicularis muscle and by virtue of the associated granulomas established the diagnosis of Melkersson-Rosenthal syndrome. CD4 helper and CD8 suppressor T-lymphocytes were equally represented. CD20 B-lymphocytes were exceedingly sparse. Conspicuous CD1a-positive Langerhans{\textquoteright} cells were present in the epidermis, sometimes formed subepithelial loose aggregates and were also incorporated in the granulomas. The differential diagnosis includes the far more common condition of acne rosacea. Management of Melkersson-Rosenthal syndrome, and of angioedema in general, is reviewed.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000088},
	author = {Chen, Xi and Jakobiec, Frederick A and Yadav, Prashant and Werdich, Xiang Q and Fay, Aaron}
}
@article {1417552,
	title = {Generation of Tumor Antigen-Specific Cytotoxic T Lymphocytes from Pluripotent Stem Cells},
	journal = {Methods Mol Biol},
	volume = {1884},
	year = {2019},
	month = {2019},
	pages = {43-55},
	abstract = {Immunotherapy is a developing but very promising arsenal to treat cancer. Acquiring a more potent and effective approach in cancer immunotherapy is always the ultimate pursuance. CTL-based therapies are highly acclaimed recently due to its direct killing property. However, difficulty in obtaining adequate number of CTLs is still a major obstacle. In previous studies, it is shown that pluripotent stem cell-derived cytotoxic T lymphocytes (CTL)-especially the genetically engineered tumor antigen-specific CTLs-may serve as a good candidate for this goal. Here we introduce a novel approach in generating tumor antigen-specific CTLs from induced pluripotent stem cells (iPSCs) by using both in vitro and in vivo priming mechanisms for the tumor management in a murine melanoma model.},
	issn = {1940-6029},
	doi = {10.1007/978-1-4939-8885-3_3},
	author = {Chen, Xiaoniao and Lei, Fengyang and Wang, Liqiang and Xiong, Xiaofang and Song, Jianxun}
}
@article {1603839,
	title = {Risk Factors and Their Diagnostic Values for Ocular Metastases in Gastric Adenocarcinoma},
	journal = {Cancer Manag Res},
	volume = {13},
	year = {2021},
	month = {2021},
	pages = {5835-5843},
	abstract = {Objective: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma. Methods: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients. Results: Chi-square tests showed significant between-groups difference in gender composition (P \&lt; 0.05), but not in age or histological grade (P \&gt; 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P \&lt; 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P \&lt; 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P \&lt; 0.001). Conclusion: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.},
	issn = {1179-1322},
	doi = {10.2147/CMAR.S311474},
	author = {Chen, Yue and Yang, Yan-Chang and Tang, Li-Ying and Ge, Qian-Min and Shi, Wen-Qing and Su, Ting and Shu, Hui-Ye and Pan, Yi-Cong and Liang, Rong-Bin and Li, Qiu-Yu and Shao, Yi}
}
@article {1593843,
	title = {Genetic associations of central serous chorioretinopathy: a systematic review and meta-analysis},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {1542-1548},
	abstract = {AIMS: To identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: We searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95\% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias. RESULTS: Totally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80{\texttimes}10-5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44{\texttimes}10-15). Among them, only TNFRSF10A rs13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2 and CFH showed opposite trends in the SNP associations. CONCLUSIONS: This study confirmed the associations of ARMS2, CFH and TNFRSF10A with CSCR, and revealed that ARMS2, CFH and TNFRSF10A may affect different phenotypic expressions of CSCR, nAMD and PCV.},
	keywords = {Central Serous Chorioretinopathy, Complement Factor H, Fluorescein Angiography, Genetic Predisposition to Disease, Genotype, Humans, Polymorphism, Single Nucleotide, Receptors, TNF-Related Apoptosis-Inducing Ligand},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-318953},
	author = {Chen, Zhen Ji and Lu, Shi Yao and Rong, Shi Song and Ho, Mary and Ng, Danny Siu-Chun and Chen, Haoyu and Gong, Bo and Yam, Jason C and Young, Alvin L and Brelen, Marten and Tham, Clement C and Pang, Chi Pui and Chen, Li Jia}
}
@article {1016021,
	title = {Interleukin-7 and -15 maintain pathogenic memory Th17 cells in autoimmunity},
	journal = {J Autoimmun},
	volume = {77},
	year = {2017},
	month = {2017 Feb},
	pages = {96-103},
	abstract = {Th17\&nbsp;cells are principal mediators of many autoimmune conditions. Recently, memory Th17\&nbsp;cells have been revealed as crucial in mediating the chronicity of various refractory autoimmune disorders; however, the underlying mechanisms maintaining memory Th17\&nbsp;cells have remained elusive. Here, using a preclinical model of ocular autoimmune disease we show that both IL-7 and IL-15 are critical for maintaining pathogenic memory Th17\&nbsp;cells. Neutralization of these cytokines leads to substantial reduction of memory Th17\&nbsp;cells; both IL-7 and IL-15 provide survival signals via activating STAT5, and IL-15 provides additional proliferation signals via activating both STAT5 and Akt. Topical neutralization of ocular IL-7 or IL-15 effectively reduces memory Th17\&nbsp;cells at the inflammatory site and draining lymphoid tissues, while topical neutralization of IL-17 alone, the major pathogenic cytokine secreted by Th17\&nbsp;cells, does not diminish memory Th17\&nbsp;cells at the draining lymphoid tissues. Our results suggest that the effective removal of pathogenic memory Th17\&nbsp;cells via abolishing environmental IL-7 or IL-15 is likely to be a novel strategy in the treatment of autoimmune diseases.},
	issn = {1095-9157},
	doi = {10.1016/j.jaut.2016.11.003},
	author = {Chen, Yihe and Chauhan, Sunil K and Tan, Xuhua and Dana, Reza}
}
@article {1647903,
	title = {Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice},
	journal = {Nat Commun},
	volume = {13},
	number = {1},
	year = {2022},
	month = {2022 Jul 29},
	pages = {4418},
	abstract = {The inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we use a systems\&nbsp;genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST show improved regeneration of the corticospinal tract and optic nerve after spinal cord injury and optic nerve crush, which is accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the utility of a systems biology approach involving integrative genomics and bio-informatics to prioritize hypotheses relevant to CNS repair.},
	issn = {2041-1723},
	doi = {10.1038/s41467-022-31960-7},
	author = {Cheng, Yuyan and Yin, Yuqin and Zhang, Alice and Bernstein, Alexander M and Kawaguchi, Riki and Gao, Kun and Potter, Kyra and Gilbert, Hui-Ya and Ao, Yan and Ou, Jing and Fricano-Kugler, Catherine J and Goldberg, Jeffrey L and He, Zhigang and Woolf, Clifford J and Sofroniew, Michael V and Benowitz, Larry I and Geschwind, Daniel H}
}
@article {1351147,
	title = {Human CFEOM1 mutations attenuate KIF21A autoinhibition and cause oculomotor axon stalling},
	journal = {Neuron},
	volume = {82},
	number = {2},
	year = {2014},
	month = {2014 Apr 16},
	pages = {334-49},
	abstract = {The ocular motility disorder "Congenital fibrosis of the extraocular muscles type 1" (CFEOM1) results from heterozygous mutations altering the motor and third coiled-coil stalk of the anterograde kinesin, KIF21A. We demonstrate that Kif21a knockin mice harboring the most common human mutation develop CFEOM. The developing axons of the oculomotor nerve{\textquoteright}s superior division stall in the proximal nerve; the growth cones enlarge, extend excessive filopodia, and assume random trajectories. Inferior division axons reach the orbit but branch ectopically. We establish a gain-of-function mechanism and find that human motor or stalk mutations attenuate Kif21a autoinhibition, providing in vivo evidence for mammalian kinesin autoregulation. We identify Map1b as a Kif21a-interacting protein and report that Map1b$^{-}$/$^{-}$ mice develop CFEOM. The interaction between Kif21a and Map1b is likely to play a critical role in the pathogenesis of CFEOM1 and highlights a selective vulnerability of the developing oculomotor nerve to perturbations of the axon cytoskeleton.},
	keywords = {Age Factors, Animals, Animals, Newborn, Axons, Cell Count, Disease Models, Animal, Embryo, Mammalian, Eye Diseases, Hereditary, Eye Movements, Fibrosis, Gene Expression Regulation, Green Fluorescent Proteins, HEK293 Cells, Humans, Kinesin, Mice, Mice, Transgenic, Microtubule-Associated Proteins, Mutation, Neural Pathways, Ocular Motility Disorders, Oculomotor Nerve},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2014.02.038},
	author = {Cheng, Long and Desai, Jigar and Miranda, Carlos J and Duncan, Jeremy S and Qiu, Weihong and Nugent, Alicia A and Kolpak, Adrianne L and Wu, Carrie C and Drokhlyansky, Eugene and DeLisle, Michelle M and Chan, Wai-Man and Wei, Yan and Propst, Friedrich and Reck-Peterson, Samara L and Fritzsch, Bernd and Engle, Elizabeth C}
}
@article {1364594,
	title = {Short-term topical bevacizumab in the treatment of stable corneal neovascularization},
	journal = {Am J Ophthalmol},
	volume = {154},
	number = {6},
	year = {2012},
	month = {2012 Dec},
	pages = {940-948.e1},
	abstract = {PURPOSE: To evaluate the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization. DESIGN: Prospective, nonrandomized, interventional case series. METHODS: setting: Institutional, multicenter clinical trial. study population: Twenty eyes from 20 patients with stable corneal neovascularization. intervention procedures: Patients were treated with topical 1.0\% bevacizumab for 3 weeks and were monitored for a total of 24 weeks. main outcome measures: Primary outcome measures included: neovascular area, defined as the area of the corneal vessels themselves; vessel caliber, defined as the mean corneal vessel diameter; and invasion area, defined as the fraction of the total cornea into which the vessels extended. The occurrence of ocular and systemic adverse events was monitored closely. RESULTS: As compared with the baseline visit, patients exhibited a statistically significant improvement in neovascular area by week 6 (P = .007) and in vessel caliber by week 12 (P = .006). At the final visit, neovascular area, vessel caliber, and invasion area were reduced by 47.5\%, 36.2\%, and 20\%, respectively. The decreases in neovascular area and vessel caliber were statistically significant (P \&lt; .001 and P = .003, respectively); however, the reduction in invasion area did not reach statistical significance (P = .06). There were no significant changes in the secondary outcomes, and there were no adverse events. CONCLUSIONS: Short-term topical bevacizumab treatment reduced the extent of stable corneal neovascularization as measured by neovascular area and vessel caliber with no associated adverse events. Interestingly, the degree of treatment efficacy was inversely proportional to the baseline invasion area.},
	keywords = {Administration, Topical, Adult, Aged, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Bevacizumab, Blood Pressure, Cornea, Corneal Neovascularization, Female, Humans, Intraocular Pressure, Male, Middle Aged, Prospective Studies, Treatment Outcome, Vascular Endothelial Growth Factor A, Visual Acuity, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2012.06.007},
	author = {Cheng, Sheng-Fu and Dastjerdi, Mohammad H and Ferrari, Giulio and Okanobo, Andre and Bower, Kraig S and Ryan, Denise S and Amparo, Francisco and Stevenson, William and Hamrah, Pedram and Nallasamy, Nambi and Dana, Reza}
}
@article {1814331,
	title = {Editorial: Stem cell-derived retinal and brain organoid culture for disease modeling},
	journal = {Front Cell Neurosci},
	volume = {18},
	year = {2024},
	month = {2024},
	pages = {1367482},
	issn = {1662-5102},
	doi = {10.3389/fncel.2024.1367482},
	author = {Cheng, Lin and Caldwell, Maeve Ann and Cho, Kin-Sang and Mellough, Carla B}
}
@article {1586188,
	title = {A smartphone ocular alignment measurement app in school screening for strabismus},
	journal = {BMC Ophthalmol},
	volume = {21},
	number = {1},
	year = {2021},
	month = {2021 Mar 25},
	pages = {150},
	abstract = {BACKGROUND: Strabismus is the leading risk factor for amblyopia, which should be early detected for minimized visual impairment. However, traditional school screening for strabismus can be challenged due to several factors, most notably training, mobility and cost. The purpose of our study is to evaluate the feasibility of using a smartphone application in school vision screening for detection of strabismus. METHODS: The beta smartphone application, EyeTurn, can measure ocular misalignment by computerized Hirschberg test. The application was used by a school nurse in a routine vision screening for 133 elementary school children. All app measurements were reviewed by an ophthalmologist to assess the rate of successful measurement and were flagged for in-person verification with prism alternating cover test (PACT) using a 2.4Δ threshold (root mean squared error of the app). A receiver operating characteristic (ROC) curve was used to determine the best sensitivity and specificity for an 8Δ threshold (recommended by AAPOS) with the PACT measurement as ground truth. RESULTS: The nurse obtained at least one successful app measurement for 93\% of children (125/133). 40 were flagged for PACT, of which 6 were confirmed to have strabismus, including 4 exotropia (10△, 10△, 14△ and 18△), 1 constant esotropia (25△) and 1 accommodative esotropia (14△). Based on the ROC curve, the optimum threshold for the app to detect strabismus was determined to be 3.0△, with the best sensitivity (83.0\%), specificity (76.5\%). With this threshold the app would have missed one child with accommodative esotriopia, whereas conventional screening missed 3 cases of intermittent extropia. CONCLUSIONS: Results support feasibility of use of the app by personnel without professional training in routine school screenings to improve detection of strabismus.},
	issn = {1471-2415},
	doi = {10.1186/s12886-021-01902-w},
	author = {Cheng, Wenbo and Lynn, Marissa H and Pundlik, Shrinivas and Almeida, Cheryl and Luo, Gang and Houston, Kevin}
}
@article {1688271,
	title = {Using a smartphone app in the measurement of posture-related pupil center shift on centration during corneal refractive surgery},
	journal = {Front Cell Dev Biol},
	volume = {11},
	year = {2023},
	month = {2023},
	pages = {1174122},
	abstract = {Purpose: Pupil center is an important anchor point in corneal refractive surgery, which may affect by body position. This study investigated the feasibility of using a smartphone application in measurement of posture-related pupil center shifts. Methods: Images of undilated eyes were captured for 25 participants (age: 18-38\&nbsp;years) at a distance of 40\&nbsp;cm in four body positions (seated, supine, right lateral, and left lateral) under controlled lighting conditions. During taking images, a smartphone application was used to guide positioning without head rotation and tilt. From the images, the location of the pupil center and pupil diameter with respect to the limbus boundary were measured. Results: According to the data obtained by the smartphone application, pupil center was located slightly nasal and superior to the limbus center in the seated position, and it shifted more nasally and superiorly (p \&lt; 0.001, OD 0.54 {\textpm} 0.11\&nbsp;mm, OS 0.57 {\textpm} 0.14\&nbsp;mm) in the supine position. When body position switched between left and right lateral positions, the pupil centers of both eyes shifted along the direction of gravity (p \&lt; 0.05), and no significant shift occurred along the longitudinal axis. Moreover, pupil constriction was observed when the body position changed from seated to supine position (p \&lt; 0.001, OD 0.64 {\textpm} 0.57\&nbsp;mm, OS 0.63 {\textpm} 0.58\&nbsp;mm). Conclusion: Posture-related pupil center shift may be larger than the error tolerance of centration in corneal refractive surgery, which might be difficult to measure by the existing instruments. An accessible application is necessary for evaluating the shift of pupil center and guiding centration during the surgery.},
	issn = {2296-634X},
	doi = {10.3389/fcell.2023.1174122},
	author = {Cheng, Wenbo and Li, Li and Luo, Gang and Wang, Yan}
}
@article {1302189,
	title = {Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury},
	journal = {PLoS One},
	volume = {13},
	number = {2},
	year = {2018},
	month = {2018},
	pages = {e0191853},
	abstract = {Epigenetic predisposition is thought to critically contribute to adult-onset disorders, such as retinal neurodegeneration. The histone methyltransferase, enhancer of zeste homolog 2 (Ezh2), is transiently expressed in the perinatal retina, particularly enriched in retinal ganglion cells (RGCs). We previously showed that embryonic deletion of Ezh2 from retinal progenitors led to progressive photoreceptor degeneration throughout life, demonstrating a role for embryonic predisposition of Ezh2-mediated repressive mark in maintaining the survival and function of photoreceptors in the adult. Enrichment of Ezh2 in RGCs leads to the question if Ezh2 also mediates gene expression and function in postnatal RGCs, and if its deficiency changes RGC susceptibility to cell death under injury or disease in the adult. To test this, we generated mice carrying targeted deletion of Ezh2 from RGC progenitors driven by Math5-Cre (mKO). mKO mice showed no detectable defect in RGC development, survival, or cell homeostasis as determined by physiological analysis, live imaging, histology, and immunohistochemistry. Moreover, RGCs of Ezh2 deficient mice revealed similar susceptibility against glaucomatous and acute optic nerve trauma-induced neurodegeneration compared to littermate floxed or wild-type control mice. In agreement with the above findings, analysis of RNA sequencing of RGCs purified from Ezh2 deficient mice revealed few gene changes that were related to RGC development, survival and function. These results, together with our previous report, support a cell lineage-specific mechanism of Ezh2-mediated gene repression, especially those critically involved in cellular function and homeostasis.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0191853},
	author = {Cheng, Lin and Wong, Lucy J and Yan, Naihong and Han, Richard C and Yu, Honghua and Guo, Chenying and Batsuuri, Khulan and Zinzuwadia, Aniket and Guan, Ryan and Cho, Kin-Sang and Chen, Dong Feng}
}
@article {313196,
	title = {Corneal perforation by an astigmatic keratotomy performed with an optical coherence tomography-guided femtosecond laser.},
	journal = {J Cataract Refract Surg},
	volume = {40},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {1224-7},
	abstract = {UNLABELLED: We present a case of corneal perforation secondary to an intrastromal astigmatic keratotomy performed with an optical coherence tomography-guided femtosecond laser. The keratotomy was concomitant with cataract surgery and resulted in a flat anterior chamber prior to the start of lens extraction. Interrupted nylon sutures were placed to seal the keratotomy prior to phacoemulsification. Escape of cavitation bubbles into the anterior chamber or the liquid interface can alert the surgeon to the possibility of unintended perforation of the endothelium or the epithelium, respectively. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2014.04.021},
	author = {Cherfan, Daniel G and Melki, Samir A}
}
@article {1470998,
	title = {Earlier use of systemic immunosuppression is associated with fewer ophthalmic surgeries in paediatric non-infectious uveitis},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {938-942},
	abstract = {BACKGROUND/AIMS: There is a paucity of large trials investigating the effect of management strategies for paediatric non-infectious uveitis on complications requiring surgery. The purpose of our study is to investigate whether earlier initiation of systemic immunosuppression in paediatric non-infectious uveitis is associated with fewer ophthalmic surgeries. METHODS: A retrospective review was conducted on 48 children with non-infectious uveitis assessed in 1998-2013. Patients were divided into uveitis diagnosed before December 2008 (group 1) and after January 2009 (group 2). Duration from uveitis onset to methotrexate initiation (U-MTX) and biological addition (U-Biologic) were reviewed. Follow-up visits with topical corticosteroids \&gt;3 times daily and active uveitis (>=1+ cells) during 3.5 years were documented. The main outcome measure was the need for >=1 ophthalmic surgery at 3.5 years. RESULTS: In group 1, 69.5\% of patients required >=1 ophthalmic surgery at 3.5 years versus 26.9\% in group 2 (p=0.005). U-MTX was 28.9{\textpm}11.8 weeks and 14.2{\textpm}10.0 weeks for groups 1 and 2 (p=0.028). U-Biologic was 134.6{\textpm}46.0 weeks and 82.3{\textpm}43.3 weeks for groups 1 and 2 (p=0.0016). Corticosteroid use \&gt;3 times daily was 85.9{\textpm}52.7 weeks and 14.6{\textpm}11.1 weeks for groups 1 and 2. Multivariate regression showed methotrexate initiation within 6 months of uveitis onset lowered the likelihood of needing ophthalmic surgery at 3.5 years (OR=6.2, 95\% CI 1.2 to 33.4; p=0.033). Univariate regression demonstrated biological addition within 18 months of uveitis onset reduced the likelihood of requiring ophthalmic surgery (OR 12.57, 95\% CI 1.28 to 123.48; p=0.030). CONCLUSION: Earlier control of uveitis by addition of immunosuppressive therapy reduced the need for ophthalmic surgery.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-314875},
	author = {Cheung, Crystal Sin Yi and Mireskandari, Kamiar and Ali, Asim and Silverman, Earl and Tehrani, Nasrin}
}
@article {1439846,
	title = {Intraocular Lens Techniques in Pediatric Eyes with Insufficient Capsular Support: Complications and Outcomes},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 May 28},
	pages = {1-10},
	abstract = {Intraocular lens (IOL) implantation in pediatric eyes with insufficient capsular support is challenging and there are multiple IOL options. These include placement of an IOL within the capsular bag with a capsular tension ring, a scleral-fixated posterior-chamber IOL (PCIOL) with or without capsular tension segment or ring, an intra-scleral fixated IOL, an iris-sutured PCIOL, or an anterior chamber iris-fixated IOL. We reviewed 48 articles and 1 published abstract describing the surgical techniques, complications and visual outcomes of different IOL options in the management of aphakic pediatric eyes with insufficient capsular support. The present review found that the visual acuity outcomes of various IOLs are comparable. Furthermore, each .},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620809},
	author = {Cheung, Crystal Sy and VanderVeen, Deborah K}
}
@article {1483596,
	title = {Prenatal diagnosis of intraconal lymphatic malformation on fetal MRI},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Jan 23},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.12.005},
	author = {Cheung, Crystal Sy and Yang, Edward and Robertson, Richard L and Mantagos, Iason S}
}
@article {1347432,
	title = {Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial},
	journal = {Ophthalmology},
	volume = {126},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {540-549},
	abstract = {PURPOSE: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy. DESIGN: Randomized sham-controlled clinical trial. PARTICIPANTS: Ninety-nine study eyes of 67 eligible participants were enrolled. METHODS: Single-masked randomized clinical trial of 24 months{\textquoteright} duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure. MAIN OUTCOME MEASURES: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups. RESULTS: Among the 67 participants who were randomized (mean age, 62{\textpm}8.9 years; 41 women [61\%]; 58 white persons [86\%]), 65 (97\%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31\% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05{\textpm}0.03 mm (P\&nbsp;= 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r\&nbsp;= 0.86; P \&lt; 0.0001). The mean retinal sensitivity loss of the sham group was 45\% greater than that of the treated group (decrease, 15.81{\textpm}8.93 dB; P\&nbsp;= 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P\&nbsp;= 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4\%) in the sham group and 2 of 48 persons (4\%) in the treated group. CONCLUSIONS: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.09.041},
	author = {Chew, Emily Y and Clemons, Traci E and Jaffe, Glenn J and Johnson, Charles A and Farsiu, Sina and Lad, Eleonora M and Guymer, Robyn and Rosenfeld, Philip and Hubschman, Jean-Pierre and Constable, Ian and Wiley, Henry and Singerman, Lawrence J and Gillies, Mark and Comer, Grant and Blodi, Barbara and Eliott, Dean and Yan, Jiong and Bird, Alan and Friedlander, Martin and Macular Telangiectasia Type 2-Phase 2 CNTF Research Group}
}
@article {541306,
	title = {Temporal Artery Calciphylaxis Presenting as Temporal Arteritis in a Case of Rhinoorbitocerebral Mucormycosis.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {5},
	year = {2015},
	month = {2015 Sep-Oct},
	pages = {e132-5},
	abstract = {Mucormycosis is a rare often fatal opportunistic fungal infection. It is typically described in patients with diabetes in ketoacidotic status and is rare in renal transplant recipients. Calciphylaxis is a rare and highly morbid disease of vascular calcification affecting patients with end-stage renal disease (ESRD). The first case of a renal transplant recipient who was inflicted with both rhinoorbitocerebral mucormycosis and calciphylaxis is reported. A 45-year-old man presented with 2-day history of left upper blepharoptosis, periorbital pain, left-sided headache, binocular diplopia, and left V2 numbness. He had undergone renal transplant for ESRD 7 months earlier with resultant immunosuppressive therapy. MRI and nasal biopsy confirmed rhinoorbitocerebral mucormycosis. Immunosuppressive therapy was stopped and antifungal therapy begun. He had orbital exenteration for progressive rhinoorbitocerebral mucormycosis. Two months later, the patient reported new-onset intermittent bitemporal headache and bilateral swollen, tender temporal arteries. Temporal artery biopsy revealed features consistent with calciphylaxis. Clinical presentation, treatment course, and follow up are discussed.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000181},
	author = {Chi, Mijung and Kim, H Jane and Basham, Ryan and Yoon, Michael K and Vagefi, Reza and Kersten, Robert C}
}
@article {1405411,
	title = {PR1P ameliorates neurodegeneration through activation of VEGF signaling pathway and remodeling of the extracellular environment},
	journal = {Neuropharmacology},
	volume = {148},
	year = {2019},
	month = {2019 Apr},
	pages = {96-106},
	abstract = {Neurodegenerative diseases affect millions of people worldwide. Optic neuropathies are the most commonly occurring neurodegenerative diseases, characterized by progressive retinal ganglion cell (RGC) degeneration. We recently reported that Prominin-1, a protein found on the surface of stem cells, interacts with VEGF and enhances its activity. VEGF is known to have various protective roles in the nervous system. Subsequently, we have developed a 12-mer peptide derived from Prominin-1, named PR1P, and investigated its effects on neuronal survival of damaged RGCs in a rat model of optic nerve crush (ONC). PR1P prevented RGC apoptosis resulting in improvement of retinal function in the rat ONC model. PR1P treatment significantly increased phosphorylation of ERK and AKT and expression its downstream proteins c-fos and Egr-1 in the retina. Additionally, PR1P beneficially increased the MMP-9/TIMP-1 ratio and promoted glial activation in the retina of ONC rats. Thus, PR1P displayed neuroprotective effects through enhanced VEGF-driven neuronal survival and reconstruction of the extracellular environment in ONC model. Our data indicate that PR1P may be a promising new clinical candidate for the treatment of neurodegenerative diseases.},
	issn = {1873-7064},
	doi = {10.1016/j.neuropharm.2018.12.029},
	author = {Chi, Zai-Long and Adini, Avner and Birsner, Amy E and Bazinet, Lauren and Akula, James D and D{\textquoteright}Amato, Robert J}
}
@article {1511486,
	title = {Evolution of vancomycin-resistant during colonization and infection in immunocompromised pediatric patients},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	number = {21},
	year = {2020},
	month = {2020 May 26},
	pages = {11703-11714},
	abstract = {Patients with hematological malignancies or undergoing hematopoietic stem cell transplantation are vulnerable to colonization and infection with multidrug-resistant organisms, including vancomycin-resistant (VREfm). Over a 10-y period, we collected and sequenced the genomes of 110 VREfm isolates from gastrointestinal and blood cultures of 24 pediatric patients undergoing chemotherapy or hematopoietic stem cell transplantation for hematological malignancy at St. Jude Children{\textquoteright}s Research Hospital. We used patient-specific reference genomes to identify variants that arose over time in subsequent gastrointestinal and blood isolates from each patient and analyzed these variants for insight into how VREfm adapted during colonization and bloodstream infection within each patient. Variants were enriched in genes involved in carbohydrate metabolism, and phenotypic analysis identified associated differences in carbohydrate utilization among isolates. In particular, a Y585C mutation in the sorbitol operon transcriptional regulator was associated with increased bacterial growth in the presence of sorbitol. We also found differences in biofilm-formation capability between isolates and observed that increased biofilm formation correlated with mutations in the putative capsular polysaccharide () biosynthetic locus, with different mutations arising independently in distinct genetic backgrounds. Isolates with mutations showed improved survival following exposure to lysozyme, suggesting a possible reason for the selection of capsule-lacking bacteria. Finally, we observed mutations conferring increased tolerance of linezolid and daptomycin in patients who were treated with these antibiotics. Overall, this study documents known and previously undescribed ways that VREfm evolve during intestinal colonization and subsequent bloodstream infection in immunocompromised pediatric patients.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1917130117},
	author = {Chilambi, Gayatri Shankar and Nordstrom, Hayley R and Evans, Daniel R and Ferrolino, Jose A and Hayden, Randall T and Mar{\'o}n, Gabriela M and Vo, Anh N and Gilmore, Michael S and Wolf, Joshua and Rosch, Jason W and Van Tyne, Daria}
}
@article {1603849,
	title = {Effect of Sequential and Simultaneous Patching Regimens in Unilateral Amblyopia},
	journal = {Am J Ophthalmol},
	volume = {233},
	year = {2022},
	month = {2022 01},
	pages = {48-56},
	abstract = {PURPOSE: Many clinicians treat unilateral amblyopia with glasses alone and initiate patching when needed; others start glasses and patching simultaneously. In this study, we reviewed the outcomes of the two approaches at our institution. DESIGN: Retrospective nonrandomized clinical trial. METHODS: Setting: Institutional practice. PATIENT POPULATION: All patients diagnosed with amblyopia at Boston Children{\textquoteright}s Hospital between 2010 and 2014. INCLUSION CRITERIA: Unilateral amblyopia (visual acuity (VA) 20/40 to 20/200 with interocular difference >=3 lines,) age 3 to 12 years, with a 6-month follow-up visit. EXCLUSION CRITERIA: Deprivation amblyopia, prior amblyopia treatment, treatment other than patching, surgery. Patients were categorized as "simultaneous treatment" (concurrent glasses and patching therapy at their first visit) or "sequential treatment" (glasses alone at first visit, followed by patching therapy at second visit.) Observation procedures: Patient demographics, VA, and stereopsis were compared. OUTCOME MEASURES: VA and stereopsis at the last visit on treatment. RESULTS: We identified 98 patients who met inclusion criteria: 36 received simultaneous treatment and 62 sequential treatment. Median amblyopic eye VA improved similarly between the simultaneous (∆0.40; interquartile range [IQR], 0.56-0.30 logMAR) and sequential (∆0.40; IQR, 0.52-0.27 logMAR) groups. Patients without stereopsis at first visit had better stereopsis outcomes with sequential treatment (5.12 [IQR, 4.00-7.51] log stereopsis) compared with simultaneous treatment (8.01 [IQR, 5.65-9.21]) log stereopsis, P = 0.046). CONCLUSIONS: VA improved approximately 4 lines regardless of treatment type. For children without stereopsis at first presentation, sequential patching yielded better stereopsis outcomes. These findings require further validation and highlight the importance of evaluating stereopsis in future studies.},
	keywords = {Amblyopia, Child, Child, Preschool, Follow-Up Studies, Humans, Retrospective Studies, Sensory Deprivation, Treatment Outcome, Vision, Binocular},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.07.012},
	author = {Chinn, Ryan N and Michalak, Suzanne M and Shoshany, Talia N and Bishop, Kaila and Staffa, Steven J and Hunter, David G}
}
@article {1761986,
	title = {Amblyopia treatment outcomes in patients with neurodevelopmental disorders},
	journal = {J AAPOS},
	volume = {27},
	number = {5},
	year = {2023},
	month = {2023 Oct},
	pages = {276.e1-276.e8},
	abstract = {PURPOSE: To compare amblyopia treatment outcomes between patients with neurodevelopmental disorders and their typically developing peers. METHODS: Of 2,311 patients diagnosed with amblyopia between 2010 and 2014 at Boston Children{\textquoteright}s Hospital, 460 met inclusion criteria (age 2-12 with anisometropic, strabismic, or mixed amblyopia [interocular difference (IOD) >=2 lines]). Treatment and visual outcomes were analyzed according to neurodevelopmental status: neurodevelopmental delay (DD) versus typical development (TD). RESULTS: The DD group (n = 54) and TD group (n = 406) were similar in demographics, amblyogenic risk factors, baseline visual measures, prescribed therapy, and adherence (P >= 0.10). Between-visit follow-up time was longer for the DD group (0.65 [0.42- 0.97] years) than for the TD group (0.5 [0.36-0.82] years; P = 0.023). IOD improved similarly in each group by the last visit (DD, -0.15 logMAR [-0.31 to -0.02]; TD, -0.2 logMAR [-0.38 to -0.1]; P\&nbsp;= 0.09). Each group reached amblyopia resolution by the last visit at similar frequencies (DD, 23/54 [43\%]; TD, 211/406 [52\%]; P \&gt; 0.2). DD diagnosis did not independently influence amblyopia resolution (HR, 0.77; 95\% CI, 0.53-1.12; P = 0.17), but each additional month of interval time between follow-up visits reduced the likelihood of resolution by 2.7\% (HR, 0.67; 95\% CI, 0.51-0.87; P = 0.003). CONCLUSIONS: Patients with DD and those with TD responded similarly to amblyopia therapy; however, follow-up intervals were longer in patients with DD and correlated with the likelihood of persistent amblyopia, suggesting that greater efforts at assuring follow-up may benefit patients with DD.},
	keywords = {Amblyopia, Child, Child, Preschool, Follow-Up Studies, Humans, Neurodevelopmental Disorders, Risk Factors, Sensory Deprivation, Treatment Outcome, Visual Acuity},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.07.014},
	author = {Chinn, Ryan N and Wilkinson, Carol L and Staffa, Steven J and Michalak, Suzanne M and Shoshany, Talia N and Bishop, Kaila and Hunter, David G and Gaier, Eric D}
}
@article {1619416,
	title = {Repeatability of the Accommodative Response Measured by the Grand Seiko Autorefractor in Children With and Without Amblyopia and Adults},
	journal = {Am J Ophthalmol},
	volume = {236},
	year = {2022},
	month = {2022 04},
	pages = {221-231},
	abstract = {PURPOSE: To assess test-retest repeatability of the accommodative response (AR) in children with and without amblyopia and adults using the Grand Seiko autorefractor. DESIGN: Prospective reliability assessment. METHODS: Test-retest of accommodation was obtained while participants viewed 20/150 sized letters at 33 cm using the Grand Seiko autorefractor in children 5 to \&lt;11 years with amblyopia (n=24) and without amblyopia (n=36), and adults 18 to \&lt;35 years (n=34). Bland-Altman 95\% limits of agreement (LOA) and intraclass correlation coefficients (ICCs) were used to assess repeatability and reliability. The AR between the fellow and amblyopic eyes of children with amblyopia and eye 1 and eye 2 of the visually normal participants was assessed using group comparisons. RESULTS: The 95\% LOA of the AR was greatest in the amblyopic eyes (-1.25 diopters [D], 1.62 D) of children with amblyopia. The 95\% LOA were similar between the fellow eyes (-0.88 D, 0.74 D) of children with amblyopia and both eyes of the children without amblyopia (eye 1: -0.68 D, 0.71 D; eye 2: -0.59 D, 0.70 D) and the adults (eye 1: 95\% LOA\&nbsp;=\&nbsp;-0.49 D, 0.45 D; eye 2: LOA\&nbsp;=\&nbsp;-0.66 D, 0.67 D). ICCs revealed the Grand Seiko autorefractor as a reliable instrument for measuring AR. CONCLUSIONS: The Grand Seiko autorefractor was more repeatable and reliable when measuring the AR in children and adults without amblyopia than in the amblyopic eye in children with amblyopia. It is recommended that multiple measures of the AR be obtained in amblyopic eyes to improve the precision of measures.},
	keywords = {Accommodation, Ocular, Adult, Amblyopia, Child, Eye, Humans, Prospective Studies, Reproducibility of Results},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.10.019},
	author = {Chinn, Ryan N and Raghuram, Aparna and Curtiss, Molly K and Gehring, Alyssa M and De Paula, Ana Juric and Roberts, Tawna L}
}
@article {1263306,
	title = {Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility},
	journal = {Nat Commun},
	volume = {8},
	number = {1},
	year = {2017},
	month = {2017 Nov 24},
	pages = {1755},
	abstract = {Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with known sequence variants, we are able to determine that the intraocular pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype. Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. Importantly, these results demonstrate that our systems genetics approach represents an efficient method to identify genetic variation that can guide the selection of therapeutic targets.},
	issn = {2041-1723},
	doi = {10.1038/s41467-017-00837-5},
	author = {Chintalapudi, Sumana R and Maria, Doaa and Di Wang, Xiang and Bailey, Jessica N Cooke and NEIGHBORHOOD Consortium and International Glaucoma Genetics Consortium and Hysi, Pirro G and Wiggs, Janey L and Williams, Robert W and Jablonski, Monica M}
}
@article {1522737,
	title = {Eyelid Keratoacanthoma in an 86-Year-Old Man: Clinical and Histopathologic Features},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2020},
	month = {2020 Jul 23},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001721},
	author = {Chiou, Carolina and Wolkow, Natalie and Freitag, Suzanne K}
}
@article {1806701,
	title = {Melanoma Arising Beneath the Lateral Rectus Muscle in a Teenager With Ocular Melanocytosis: Possible Origin From Intrascleral Melanocytes},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2024},
	month = {2024 Feb 09},
	abstract = {Ocular melanocytosis is a well-established risk factor for choroidal melanomas but, despite its reported associations in the literature, it is infrequently discussed in relation to orbital melanomas. The authors describe a teenage patient with ocular melanocytosis who presented with an asymptomatic ipsilateral right orbital mass associated with the lateral rectus muscle. An exploratory orbitotomy revealed a lesion lightly adherent to the underlying sclera. Histopathology demonstrated a markedly atypical epithelioid melanocytic proliferation, bound by a thin rim of superficial sclera, implying an origin from intrascleral melanocytes, likely within an emissary canal. Next-generation sequencing identified GNAQ and NF1 mutations. The histopathology and molecular genetics designated the lesion as having a uveal melanoma-like profile, suggesting that it may behave as a choroidal melanoma. This case underscores the importance of the association between ocular melanocytosis and orbital melanoma and provides additional evidence for primary orbital melanoma etiopathogenesis.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002627},
	author = {Chiou, Carolina A and Lin, Lisa Y and Stagner, Anna M and Lee, Nahyoung Grace}
}
@article {1632306,
	title = {Shewanella algae Causing Pediatric Orbital Abscess With Leptomeningitis},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {4},
	year = {2022},
	month = {2022 Jul-Aug 01},
	pages = {e101-e104},
	abstract = {A 13-year-old boy presented with 3 days of left-sided periorbital pain, swelling, mucoid discharge, and fever to 103{\textdegree}F, with onset 1 day after swimming in the ocean. Within 12 hours, he experienced rapid clinical deterioration with formation of a superomedial subperiosteal abscess and an epidural abscess with leptomeningitis despite treatment with broad-spectrum intravenous antibiotics. The patient underwent urgent left orbitotomy with abscess drainage and functional endoscopic sinus surgery. Intraoperative cultures grew Shewanella algae and Escherichia coli . The patient showed marked clinical improvement following surgical intervention and tailored antibiotic therapy. This is the first reported case of orbital abscess with acute bacterial rhinosinusitis due to infection with Shewanella algae .},
	keywords = {Abscess, Acute Disease, Adolescent, Anti-Bacterial Agents, Child, Drainage, Humans, Male, Orbital Cellulitis, Orbital Diseases, Retrospective Studies, Shewanella, Sinusitis},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002138},
	author = {Chiou, Carolina A and Reshef, Edith R and Yoon, Michael K}
}
@article {1586200,
	title = {Retinal Detachment in a 40-Year-Old Man With Sturge-Weber Syndrome},
	journal = {JAMA Ophthalmol},
	year = {2021},
	month = {2021 Mar 04},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.4665},
	author = {Chiou, Carolina A and Gragoudas, Evangelos}
}
@article {1538326,
	title = {Characterization of Prelaminar Wedge-Shaped Defects in Primary Open-Angle Glaucoma},
	journal = {Curr Eye Res},
	volume = {46},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {895-902},
	abstract = {PURPOSE: To determine the clinical relevance of prelaminar wedge defects (PLWDs) detected by swept-source optical coherence tomography (SS-OCT) in primary open-angle glaucoma (POAG). MATERIALS AND METHODS: In this retrospective case-control study, PLWDs were defined as triangular-shaped defects at the surface of the optic nerve prelaminar tissue, not adjacent to blood vessels, present on cross-sectional SS-OCT scans. Two observers masked to diagnosis independently reviewed scans to detect PLWDs and lamina cribrosa defects. History of disc hemorrhage, occurring within 2\&nbsp;years prior to imaging, was obtained from chart review. One eye per subject was randomly selected. Two-sided t-tests, analysis of variance with Bonferroni correction, and multivariable logistic regression analysis were performed to explore demographic and clinical features associated with PLWDs. RESULTS: 40 POAG and 23 control eyes were included. PLWDS were found in 27.5\% of POAG (n\&nbsp;=\&nbsp;11) and 4.3\% of controls (n\&nbsp;=\&nbsp;1, p =\&nbsp;.04). Eyes with repeat SS-OCT imaging (7 POAG and 0 controls) had persistent PLWDs. More POAG eyes with PLWDs had a history of disc hemorrhage (45.5\%) than POAG eyes without PLWDs (3.4\%, p =\&nbsp;.004). On multivariable analysis, compared to POAG without PLWDs, POAG with PLWDs had increased odds of observed disc hemorrhage (OR\&nbsp;=\&nbsp;21.6, 95\% CI, 2.2-589.0, p =\&nbsp;.02) after adjusting for age, gender, visual field mean deviation and maximum intraocular pressure (IOP). POAG with PLWDs had more lamina cribrosa defects (45.5\%) than POAG without PLWDs (3.4\%, p =\&nbsp;.01) but did not differ significantly from controls (8.7\%, p =\&nbsp;.07). Compared to all patients without PLWDs, patients with PLWDs had increased odds of having lamina cribrosa defects (OR\&nbsp;=\&nbsp;44.8; 95\% CI, 6.3-703.6, p \&lt;\&nbsp;.001) after adjusting for age, gender, and maximum IOP. CONCLUSIONS: PLWDs were more frequently found in POAG than control eyes and were associated with a history of disc hemorrhage and lamina cribrosa defects. PLWDs may be a useful imaging biomarker of glaucomatous damage.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2020.1836229},
	author = {Chiou, Carolina A and Wang, Mengyu and Taniguchi, Elise V and Silva, Rafaella Nascimento E and Khoroshilov, Anna and Li, Dian and Wang, Haobing and Greenstein, Scott H and Brauner, Stacey C and Turalba, Angela V and Pasquale, Louis R and Shen, Lucy Q}
}
@article {1598068,
	title = {Teprotumumab for the treatment of mild compressive optic neuropathy in thyroid eye disease: A report of two cases},
	journal = {Am J Ophthalmol Case Rep},
	volume = {22},
	year = {2021},
	month = {2021 Jun},
	pages = {101075},
	abstract = {Purpose: To report two cases of thyroid eye disease (TED) associated compressive optic neuropathy (CON) that resolved after treatment with teprotumumab. Observation: Two patients presented with active TED resulting in mild CON with the typical corresponding visual field (VF) defects. Both patients were initiated on intravenous (IV) corticosteroid therapy but despite treatment had persistent VF defects. Both patients were then treated with teprotumumab and demonstrated marked clinical improvement and complete resolution of TED-CON VF defects early in their infusion course. Conclusions and importance: These cases suggest that teprotumumab can be a rapid and effective treatment for TED-CON, and raises the question of whether it may be superior to IV corticosteroid therapy.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2021.101075},
	author = {Chiou, Carolina A and Reshef, Edith R and Freitag, Suzanne K}
}
@article {1655729,
	title = {Membrane Frizzled-Related Protein-Related Disease Mimicking Idiopathic Intracranial Hypertension},
	journal = {J Neuroophthalmol},
	year = {2022},
	month = {2022 Oct 18},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001720},
	author = {Chiou, Carolina A and Rajabi, Farrah and Fulton, Anne B and Acsadi, Gyula and Waitzman, David M and Gaier, Eric D}
}
@article {1424799,
	title = {In Vivo Confocal Microscopy Demonstrates Increased Immune Cell Densities in Corneal Graft Rejection Correlating With Signs and Symptoms},
	journal = {Am J Ophthalmol},
	volume = {203},
	year = {2019},
	month = {2019 Jul},
	pages = {26-36},
	abstract = {PURPOSE: Diagnosis of graft rejection is based on patient symptoms and on clinical signs detected by slit-lamp biomicroscopy. This study investigated whether laser in\&nbsp;vivo confocal microscopy (IVCM) can aid in the diagnosis of corneal graft rejection by detecting cellular corneal changes that take place after transplantation. DESIGN: Prospective case-control study. SUBJECTS: Thirty-eight eyes of 38 patients with penetrating keratoplasty (15 eyes with corneal graft rejection, 23 eyes without rejection) and 9 age-matched normal controls. METHODS: Laser IVCM was performed in the corneal grafts centrally. The density of immune cells (IC) was assessed for epithelial, sub-epithelial, stromal, and endothelial layers by 2 masked observers. IC density was compared among different groups and correlated to clinical signs and symptoms of corneal graft rejection. MAIN OUTCOME MEASUREMENTS: Outcome measurement was the IC density in the corneal layers and its associations with the presence of clinical signs and symptoms of corneal graft rejection. RESULTS: The IC density was significantly different between rejected and non-rejected grafts (P\&nbsp;= 0.004) and different from that of normal controls (P\&nbsp;= 0.001). Among corneal layers, IC density was significantly higher in rejected grafts than in non-rejected grafts in only the sub-basal (611.54 {\textpm} 573.74 vs. 340.61 {\textpm} 268.60 cells/mm, respectively; P\&nbsp;= 0.049) and endothelial layers (250.62 {\textpm} 267.13 vs. 103.47 {\textpm} 81.91 cells/mm, respectively; P\&nbsp;= 0.001). Patients with decreased best corrected visual acuity, Khodadoust line, and anterior chamber cells demonstrated a significant increase in total IC density (P \&lt; 0.05), whereas patients with symptoms of irritation, light sensitivity, and pain revealed a specific increase in IC density in the sub-basal layer (P \&lt; 0.05). Patients with ocular pain had higher IC density in the epithelial layer than those without pain (P\&nbsp;= 0.03). CONCLUSIONS: Patients with corneal graft rejection demonstrate a significant increase in corneal immune cells, particularly, in the sub-basal and endothelial layers compared to patients with non-rejected grafts and controls. Although symptoms associated with endothelial rejection demonstrate a general increase in IC, pain, irritation, and light sensitivity are associated with increased IC in the sub-basal layer. Assessment of patients with corneal graft rejection by IVCM may serve as an adjunctive tool in the diagnosis and management of corneal graft rejection.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.02.013},
	author = {Chirapapaisan, Chareenun and Abbouda, Alessandro and Jamali, Arsia and M{\"u}ller, Rodrigo T and Cavalcanti, Bernardo M and Colon, Clara and Witkin, Deborah and Sahin, Afsun and Dana, Reza and Cruzat, Andrea and Hamrah, Pedram}
}
@article {1549004,
	title = {Effect of herpes simplex keratitis scar location on bilateral corneal nerve alterations: an in vivo confocal microscopy study},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {3},
	year = {2022},
	month = {2022 Mar},
	pages = {319-325},
	abstract = {AIMS: To evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM). METHODS: Central and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 peripheral scars (PS)) using IVCM. Results were compared between patients and 24 age-matched controls. CSND was correlated to corneal sensation for all locations. RESULTS: Overall patients revealed significant decrease of CSND in the central and peripheral cornea (9.13{\textpm}0.98 and 6.26{\textpm}0.53 mm/mm2, p\&lt;0.001), compared with controls (22.60{\textpm}0.77 and 9.88{\textpm}0.49 mm/mm2). CS group showed a decrease in central (8.09{\textpm}1.30 mm/mm2) and total peripheral nerves (5.15{\textpm}0.62 mm/mm2) of the affected eyes, whereas PS group demonstrated a decrease in central (10.34{\textpm}1.48 mm/mm2) and localised peripheral nerves only in the scar area (4.22{\textpm}0.77 mm/mm2) (all p\&lt;0.001). In contralateral eyes, CSND decreased in the central cornea of the CS group (16.88{\textpm}1.27, p=0.004), and in the peripheral area, mirroring the scar area in the affected eyes of the PS group (7.20{\textpm}0.87, p=0.032). Corneal sensation significantly decreased in the whole cornea of the affected, but not in contralateral eyes (p\&lt;0.001). A positive correlation between CSND and corneal sensation was found in all locations (p\&lt;0.001). CONCLUSIONS: Patients with HSV scar demonstrate bilateral CSND decrease as shown by IVCM. CSND and corneal sensation decrease in both central and peripheral cornea in affected eyes, although only in the scar area in PS group. Interestingly, diminishment of CSND was found locally in the contralateral eyes, corresponding and mirroring the scar location in the affected eyes.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316628},
	author = {Chirapapaisan, Chareenun and Muller, Rodrigo T and Sahin, Afsun and Cruzat, Andrea and Cavalcanti, Bernardo M and Jamali, Arsia and Pavan-Langston, Deborah and Hamrah, Pedram}
}
@article {1460372,
	title = {A resistance-sensing mechanical injector for the precise delivery of liquids to target tissue},
	journal = {Nat Biomed Eng},
	volume = {3},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {621-631},
	abstract = {The precision of the delivery of therapeutics to the desired injection site by syringes and hollow needles typically depends on the operator. Here, we introduce a highly sensitive, completely mechanical and cost-effective injector for targeting tissue reliably and precisely. As the operator pushes the syringe plunger, the injector senses the loss-of-resistance on encountering a softer tissue or a cavity, stops advancing the needle and delivers the payload. We demonstrate that the injector can reliably deliver liquids to the suprachoroidal space-a challenging injection site that provides access to the back of the eye-for a wide range of eye sizes, scleral thicknesses and intraocular pressures, and target sites relevant for epidural injections, subcutaneous injections and intraperitoneal access. The design of this simple and effective injector can be adapted for a broad variety of clinical applications.},
	issn = {2157-846X},
	doi = {10.1038/s41551-019-0350-2},
	author = {Chitnis, Girish D and Verma, Mohan K S and Lamazouade, Julien and Gonzalez-Andrades, Miguel and Yang, Kisuk and Dergham, Ali and Jones, Peter Anthony and Mead, Benjamin E and Cruzat, Andrea and Tong, Zhixiang and Martyn, Keir and Solanki, Aniruddh and Landon-Brace, Natalie and Karp, Jeffrey M}
}
@article {1748356,
	title = {Role of Static and Dynamic Ocular Biometrics Measured in the Dark and Light as Risk Factors for Angle Closure Progression},
	journal = {Am J Ophthalmol},
	volume = {256},
	year = {2023},
	month = {2023 Dec},
	pages = {27-34},
	abstract = {PURPOSE: To assess the role of static and dynamic ocular biometric parameters measured in the dark and light for predicting progression of primary angle closure suspect (PACS) to primary angle closure (PAC). DESIGN: Retrospective cohort study using prospective randomized controlled trial data from untreated, control eyes. METHODS: Zhongshan Angle Closure Prevention Trial subjects underwent anterior segment optical coherence tomography (AS-OCT) imaging in the dark and light. Static biometric parameters were measured, consisting of angle, iris, lens, and anterior chamber parameters. Dynamic change parameters were calculated by subtracting light measurements from dark measurements. Cox proportional hazards regression models were developed to assess risk factors for PACD progression. RESULTS: A total of 861 eyes of 861 participants were analyzed (36 progressors). On univariable analysis, TISA500 measurements in the light and dark were associated with progression (P \&lt; .001), whereas dynamic change parameters were not (P >= .08). In the primary multivariable model, older age (hazard ratio [HR]\&nbsp;=\&nbsp;1.09 per year), higher intraocular pressure (IOP) (HR\&nbsp;=\&nbsp;1.13 per mm Hg), and smaller TISA500 in the light (HR\&nbsp;=\&nbsp;1.28 per 0.01 mm2) were significantly associated with greater risk of progression (P <= .04). Dark TISA500 had similar significance (HR\&nbsp;=\&nbsp;1.28, P\&nbsp;=\&nbsp;.002) when replacing light TISA500. Risk of progression was more predictive among eyes in the lowest quartile of light TISA500 measurements (HR\&nbsp;=\&nbsp;4.56, P \&lt; .001) compared to dark measurements (HR\&nbsp;=\&nbsp;2.89, P\&nbsp;=\&nbsp;.003). CONCLUSION: Static parameters measured in the light are as predictive, and possibly more so, of angle closure progression as those measured in the dark. Ocular biometrics measured under light and dark conditions may provide additional information for risk-stratifying patients for angle closure progression.},
	keywords = {Anterior Eye Segment, Biometry, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Iris, Prospective Studies, Retrospective Studies, Risk Factors, Tomography, Optical Coherence},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.07.032},
	author = {Cho, Austin and Xu, Benjamin Y and Friedman, David S and Foster, Paul J and Jiang, Yu and Pardeshi, Anmol A and Jiang, Yuzhen and Aung, Tin and He, Mingguang}
}
@article {836776,
	title = {Endogenous Endophthalmitis in the American and Korean Population: An 8-year Retrospective Study.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Jul 26},
	pages = {1-8},
	abstract = {PURPOSE: To study the clinical features of endogenous endophthalmitis (EE) in sample patient populations from the USA and South Korea over an 8-year period. METHODS: We reviewed data from 128 eyes of 60 American and 48 Korean patients diagnosed with EE and compared their clinical characteristics. RESULTS: Fungemia and liver abscess were the most common extraocular infection sources among American (26.7\%) and Korean patients (33.3\%), respectively. Klebsiella pneumoniae and Candida species were the most common pathogens of EE in the Korean and the American patients, respectively. Endophthalmitis caused by fungi had a better visual prognosis than that caused by bacteria (p = 0.001). Vitrectomy was beneficial for eyes with EE due to virulent bacteria presenting with worse than counting finger vision. CONCLUSIONS: The predisposing conditions and responsible organisms for EE vary in different regions of the world. The visual prognosis was strongly influenced by the underlying pathogen.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2016.1195000},
	author = {Cho, Heeyoon and Shin, Yong Un and Siegel, Nicole H and Yu, Hyeong Gon and Sobrin, Lucia and Patel, Achal and Durand, Marlene L and Miller, Joan W and Husain, Deeba}
}
@article {341631,
	title = {Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring.},
	journal = {Ocul Immunol Inflamm},
	volume = {24},
	number = {2},
	year = {2016},
	month = {2016 Apr},
	pages = {194-206},
	abstract = {PURPOSE: To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). METHODS: Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. RESULTS: Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100\% and 86.9-100\% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 {\textmu}m (p = 0.01). CONCLUSIONS: Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2014.991041},
	author = {Cho, Heeyoon and Pillai, Parvathy and Nicholson, Laura and Sobrin, Lucia}
}
@article {1445347,
	title = {Dissociation kinetics of TAPBPR-MHC class I complex},
	journal = {Mol Immunol},
	volume = {114},
	year = {2019},
	month = {2019 Oct},
	pages = {661-662},
	issn = {1872-9142},
	doi = {10.1016/j.molimm.2019.05.002},
	author = {Cho, Steve and Kang, Jonghoon}
}
@article {1351148,
	title = {Focal laser photocoagulation and photodynamic therapy for lupus choroidopathy},
	journal = {Lupus},
	volume = {23},
	number = {4},
	year = {2014},
	month = {2014 Apr},
	pages = {412-6},
	abstract = {PURPOSE: To describe the results of photodynamic therapy (PDT) and/or focal laser photocoagulation in the treatment of serous retinal detachments secondary to lupus choroidopathy. METHODS: The medical records of three patients with serous detachments secondary to lupus choroidopathy who were treated with PDT and/or focal laser photocoagulation were reviewed. Concomitant systemic medical therapy as well as visual acuity and optical coherence tomography (OCT) outcomes were recorded. RESULTS: All patients received systemic immunosuppressive therapy and had control of their extraocular manifestations prior to PDT and/or laser photocoagulation. One patient received only focal laser photocoagulation and had complete resolution of the subretinal fluid on OCT. The two other patients received a combination of PDT and focal laser treatment. One had improvement in vision and resolution of subretinal fluid on OCT. The second patient, who had longstanding lupus choroidopathy and associated subretinal fluid and macular edema, had only a significant decrease in fluid on OCT but no vision improvement. CONCLUSION: In conjunction with control of systemic disease, PDT and/or focal laser photocoagulation can be successful in resolving subretinal fluid secondary to lupus choroidopathy.},
	keywords = {Adult, Choroid Diseases, Combined Modality Therapy, Female, Humans, Immunosuppressive Agents, Laser Coagulation, Lupus Erythematosus, Systemic, Macular Edema, Male, Middle Aged, Photochemotherapy, Retinal Detachment, Tomography, Optical Coherence, Treatment Outcome, Visual Acuity},
	issn = {1477-0962},
	doi = {10.1177/0961203314522339},
	author = {Cho, H Y and Nasir, H H and Sobrin, L}
}
@article {1586141,
	title = {Ophthalmic Implications of Chimeric Antigen Receptor T-Cell Therapy},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {329-334},
	abstract = {Chimeric antigen\&nbsp;receptor (CAR) T-cell therapy is a revolutionary addition to the burgeoning field of immunotherapy. CAR T-cells are engineered by combining a T-cell receptor with the antigen-binding site of an immunoglobulin that allows the hybrid cell to target antigens of interest. CAR T-cell therapy has been approved to treat various hematologic malignancies, including relapsed or refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. While the treatment efficacy is exciting, challenges remain in understanding the unique spectrum of adverse effects of CAR T-cell therapy, including cytokine release syndrome and neurotoxicity. Innovative research is underway to expand this therapy into solid tumors and fields beyond hematology and oncology. To date, there has been limited research into ophthalmic uses and considerations of CAR T-cell therapy. This review focuses on preclinical investigations into CAR T-cell therapy for retinoblastoma and uveal melanoma, as well as ophthalmic complications of CAR T-cell therapy.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1897857},
	author = {Chodnicki, Kevin D and Prasad, Sashank}
}
@article {1522726,
	title = {Adoption of Innovation in Herpes Simplex Virus Keratitis},
	journal = {Cornea},
	volume = {39 Suppl 1},
	year = {2020},
	month = {2020 Nov},
	pages = {S7-S18},
	abstract = {Herpes simplex keratitis, caused primarily by human herpes simplex virus type 1 (HSV-1), remains the most common infectious cause of unilateral blindness and vision impairment in the industrialized world. Major advances in the care of HSV keratitis have been driven in large part by the landmark Herpetic Eye Disease Study randomized clinical trials, which were among the first in ophthalmology to reflect emerging trial conventions, including multicenter subject enrollment, double-masking, placebo controls, and a priori sample size determinations. The results of these trials now form much of the evidence basis for the management of this disease. However, management patterns in clinical practice often deviate from evidence-based care. These perceived quality gaps have given rise to the evolving field of implementation science, which is concerned with the methods of promoting the application of evidence-based medicine within routine care. To overcome variations in the quality and consistency of care for HSV keratitis, a range of clinical- and technology-based innovations are proposed. The most pressing needs include the following: a rational and tractable disease classification scheme that provides an immediate link between the anatomical localization of disease (corneal epithelial, stromal, or endothelial) and the appropriate treatment, and the actualization of an electronic medical record system capable of providing evidence-based treatment algorithms at relevant points of care. The latter would also input data to population-wide disease registries to identify implementation-rich targets for quality improvement, education, and research. These innovations may allow us to reduce the human and economic burdens of this highly morbid, and often blinding, disease.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002425},
	author = {Chodosh, James and Ung, Lawson}
}
@article {341736,
	title = {Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model.},
	journal = {J Leukoc Biol},
	volume = {97},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {413-24},
	abstract = {Although corneal allotransplantation is performed in the immune-privileged cornea, many grafts are still rejected after transplantation. This study examined the role of chemokine receptor D6 expression in a corneal allograft rejection, investigated the modulation of D6 expression in cells, and determined the effect of D6 on graft survival. Interestingly, D6 was highly expressed in CD45 -: cells and the corneal epithelium of accepted corneal allografts. From the mouse corneal allograft model, TGF-β was found to play a key role in D6 up-regulation, leading to reduced CCL2, CCL5, and CCL3. To modulate D6 chemokine binding, a D6MT was developed and showed effective chemokine trapping through SPR and FACS assays. By treating corneal allografts with D6MT, the allograft survival rate was improved, and (lymph) angiogenesis was reduced. Direct allosensitization and DC LN homing was drastically reduced in the mouse corneal allograft model. These findings suggest that TGF-β is a positive regulator of D6 expression, and it is a potential therapeutic target to enhance the survival of corneal allografts.},
	issn = {1938-3673},
	doi = {10.1189/jlb.5A0414-233RR},
	author = {Choi, Wungrak and Byun, Yu Jeong and Jung, Eunae and Noh, Hyemi and Hajrasouliha, Amir R and Sadrai, Zahra and Chang, Eun Ju and Lee, Joon H and Lee, Hyung Keun}
}
@article {504016,
	title = {Full-Thickness Skin Graft as an Independent or Adjunctive Technique for Repair of Cicatricial Lower Eyelid Ectropion Secondary to Actinic Skin Changes.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {6},
	year = {2015},
	month = {2015 Nov-Dec},
	pages = {474-7},
	abstract = {PURPOSE: To retrospectively review and describe full-thickness skin graft repair of lower eyelid cicatricial ectropion secondary to actinic skin. METHODS: A retrospective, noncomparative chart review of all patients who underwent lower eyelid ectropion repair with placement of a full-thickness skin graft between June 2004 and March 2014 was conducted with IRB approval. The etiology of lower eyelid ectropion, demographics including age, gender, ethnicity, laterality, graft donor site, additional surgical procedures, graft viability, surgical success rate, complications, and clinical exam findings were summarized. RESULTS: Twenty-nine eyelids in 24 patients underwent skin grafting for repair of cicatricial ectropion secondary to actinic skin changes. Ninety six percent of patients were male and 96\% were Caucasian. Donor sites for skin grafts included upper eyelid (9, 31\%), supraclavicular skin (9, 31\%), postauricular skin (7, 24\%), inner brachial skin (2, 7\%), axilla (1, 3.5\%), and preauricular skin (1, 3.5\%). Twenty-four of 29 eyelids in the series underwent 1 or more additional procedures at the time of full-thickness skin grafting, including lateral tarsal strip (9 eyelids, 37.5\%), punctoplasty (8, 33\%), canthoplasty (7, 29\%), excision of keratinized conjunctiva (2, 8\%), transverse tarsotomy (1, 4\%), ipsilateral external dacryocystorhinostomy (3, 12.5\%), and lesion removal (1, 4\%). There was 100\% viability of the skin grafts. Overall surgical success rate was 76\%, with asymptomatic recurrence rate of 17\% and symptomatic recurrence rate of 7\%. CONCLUSION: Repair of cicatricial lower eyelid ectropion secondary to actinic skin changes may be accomplished with full-thickness skin grafting, and is often performed in conjunction with additional procedures to fully address anatomic abnormalities.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000524},
	author = {Choi, Catherine J and Bauza, Alain and Yoon, Michael K and Sobel, Rachel K and Freitag, Suzanne K}
}
@article {705051,
	title = {Eyelid Mass in Boston Keratoprosthesis Type 2.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2016},
	month = {2016 May 9},
	abstract = {Boston keratoprosthesis type 2 is used to treat severe corneal blindness secondary to cicatricial or autoimmune ocular surface disease. This case report describes an atypical eyelid mass in a 41-year-old woman with Stevens-Johnson syndrome who underwent placement of Boston keratoprosthesis type 2 in the left eye. The postoperative course was complicated by methicillin-sensitive Staphylococcus aureus keratitis and endophthalmitis requiring replacement of the keratoprosthesis. Three months thereafter, the patient presented with a progressively enlarging upper eyelid mass adjacent to the keratoprosthesis optic causing distortion of the eyelid. Excisional biopsy revealed an elongated cystic mass abutting the superior aspect of the optic. Pathologic examination was consistent with a conjunctival cyst with lipogranulomatous reaction. Removal of eyelid margins and conjunctiva, and placement of a full-thickness blepharotomy are standard steps in placement of Boston keratoprosthesis type 2, which can lead to conjunctival cysts and lipogranulomas that present as eyelid masses.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000712},
	author = {Choi, Catherine J and Stagner, Anna M and Jakobiec, Frederick A and Chodosh, James and Yoon, Michael K}
}
@article {1062816,
	title = {Patterns of visual field changes in thyroid eye disease},
	journal = {Orbit},
	volume = {36},
	number = {4},
	year = {2017},
	month = {2017 Aug},
	pages = {201-207},
	abstract = {This article provides a systematic description of visual field changes in thyroid eye disease-compressive optic neuropathy (TED-CON). A retrospective, non-comparative chart review of patients with TED-CON and documented Humphrey Visual Field 24-2 or 30-2 testing was conducted with IRB approval. Ninety-six visual fields in 68 patients were classified into 7 broad categories (superior, inferior, diffuse, temporal, nasal, central/paracentral, enlarged blind spot) and 17 mutually exclusive patterns from the Ocular Hypertension Treatment Study (OHTS) or "other." Fifty-three of 96 visual fields (55\%) showed an inferior defect using the broad categories, with the remaining 6 categories ranging from 2\% to 14\%. The five most common OHTS patterns were other (28\%), partial arcuate (28\%), partial peripheral rim (9\%), arcuate (8\%) and altitudinal (7\%). Further sub-classification showed a predominance of inferior visual field defects, ranging from 33\% to 93\% of each category. Of the 78 visual fields in these five categories combined, 52 (67\%) were inferior defects. Inferior defect is the most typical TED-CON-associated visual field change. While the OHTS categories are geared toward classification of glaucomatous patterns, the overall predominance of inferior field defects in TED-CON was clearly demonstrated. These "other" visual field changes showing central inferior defect up to but not crossing the horizontal meridian and not contiguous from blind spot to nasal meridian should be designated as "TED-CON pattern." The high proportion of visual fields falling under the "other" category, however, does demonstrate the need for a more specific and tailored visual field classification system for TED-CON.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2017.1314510},
	author = {Choi, Catherine J and Oropesa, Susel and Callahan, Alison B and Glass, Lora R and Teo, Livia and Cestari, Dean M and Kazim, Michael and Freitag, Suzanne K}
}
@article {1814421,
	title = {Characterization of the development of the high-acuity area of the chick retina},
	journal = {Dev Biol},
	year = {2024},
	month = {2024 Mar 26},
	abstract = {The fovea is a small region within the central retina that is responsible for our high acuity daylight vision. Chickens also have a high acuity area (HAA), and are one of the few species that enables studies of the mechanisms of HAA development, due to accessible embryonic tissue and methods to readily perturb gene expression. To enable such studies, we characterized the development of the chick HAA using single molecule fluorescent in situ hybridization (smFISH), along with more classical methods. We found that Fgf8 provides a molecular marker for the HAA throughout development and into adult stages, allowing studies of the cellular composition of this area over time. The radial dimension of the ganglion cell layer (GCL) was seen to be the greatest at the HAA throughout development, beginning during the period of neurogenesis, suggesting that genesis, rather than cell death, creates a higher level of retinal ganglion cells (RGCs) in this area. In contrast, the HAA acquired its characteristic high density of cone photoreceptors post-hatching, which is well after the period of neurogenesis. We also confirmed that rod photoreceptors are not present in the HAA. Analyses of cell death in the developing photoreceptor layer, where rods would reside, did not show apoptotic cells, suggesting that lack of genesis, rather than death, created the "rod-free zone" (RFZ). Quantification of each cone photoreceptor subtype showed an ordered mosaic of most cone subtypes. The changes in cellular densities and cell subtypes between the developing and mature HAA provide some answers to the overarching strategy used by the retina to create this area and provide a framework for future studies of the mechanisms underlying its formation.},
	issn = {1095-564X},
	doi = {10.1016/j.ydbio.2024.03.005},
	author = {Choi, Jiho and Joisher, Heer V and Gill, Hasreet K and Lin, Lucas and Cepko, Constance}
}
@article {634991,
	title = {Limbal Mantle Cell Lymphoma of the Conjunctiva.},
	journal = {Ophthalmology},
	volume = {123},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {377},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.11.012},
	author = {Choi, Catherine J and Stagner, Anna M and Jakobiec, Frederick A and Lee, Nahyoung Grace}
}
@article {1078726,
	title = {Conjunctival Squamous Cell Neoplasia Associated With Ocular Cicatricial Pemphigoid},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {6},
	year = {2017},
	month = {2017 Nov/Dec},
	pages = {e157-e160},
	abstract = {The purpose of this study was to describe a possible causal relationship between ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two middle-aged female patients with already diagnosed OCP were studied in regard to the subsequent onset of conjunctival squamous neoplasia. Their clinical histories, ocular examinations, clinical photographs, and results of biopsies and any ancillary immunofluorescent laboratory evaluation studies were carefully reviewed. One patient had a preinvasive squamous dysplasia and the other an invasive squamous cell carcinoma, both in the unequivocal setting of OCP with bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients had been receiving intensive immunotherapy consisting of some combination of corticosteroids, rituximab, and interferon alpha. Both patients had a positive immunofluorescent study demonstrating immunoreactants at the level of the epithelial basement membrane. Each patient had 2 earlier negative immunofluorescent studies before a third was positive. While rare, there is 1 previous report of an association between OCP and conjunctival squamous neoplasia. The current report provides more data supporting the proposal that this conjunction is more than a random event. Repeat immunofluorescent studies after an initial negative result in a patient with strong clinical signs of OCP are imperative due to the frequency of false negative studies in the context of clinically persuasive disease.},
	keywords = {Aged, Biopsy, Carcinoma, Squamous Cell, Conjunctiva, Conjunctival Neoplasms, Female, Humans, Middle Aged, Pemphigoid, Benign Mucous Membrane},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000926},
	author = {Choi, Catherine J and Jakobiec, Frederick A and Zakka, Fouad R and Foster, C Stephen and Chodosh, James and Freitag, Suzanne K}
}
@article {397781,
	title = {Margin Reflex Distance: Differences Based on Camera and Flash Positions.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {3},
	year = {2016},
	month = {2016 May-Jun},
	pages = {199-203},
	abstract = {PURPOSE: To evaluate the effect of camera flash position on the measurement of photographic margin reflex distances (MRD). METHODS: Subjects without any ophthalmic disease were prospectively enrolled after institutional review board approval. Clinical measurements of MRD1 and interpalpebral fissure were obtained. Photographs were then taken with a digital single lens reflex with built-in pop-up flash (dSLR-pop), a dSLR with lens-mounted ring flash (dSLR-ring), a point-and-shoot camera, and a smartphone, each in 4 positions: with the camera upright, rotated 90{\textdegree}, 180{\textdegree}, and 270{\textdegree}. The images were analyzed using ImageJ software to measure MRD1, interpalpebral fissure, horizontal white-to-white, and distance from nasal limbus to the corneal light reflex. RESULTS: Thirty-two eyes of 16 subjects were included (ages 27-65). When using the dSLR-ring, point-and-shoot, and smartphone, the difference between clinical and photographic MRD1 did not reach statistical significance. There was, however, a statistically significant difference in the upright position with dSLR-pop (mean difference 0.703 mm, σ = 0.984 mm, p = 0.0008). For dSLR-pop, photographic MRD1 in upright versus inverted position differed significantly (mean difference -0.562 mm, σ =0.348 mm, p \&lt; 0.0001). Photographic MRD1 between dSLR-pop and dSLR-ring showed significant difference in upright position (mean difference -0.572 mm, σ = 0.701 mm, p = 0.0002). There were no statistically significant differences between clinical and photographic interpalpebral fissure, and among white-to-white and nasal limbus to light reflex measurements in any position in all 4 cameras. CONCLUSIONS: When using photographs for measurement of MRD1, cameras with a near-coaxial light source and aperture have values that are most similar to clinical measurements.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000456},
	author = {Choi, Catherine J and Chou, Jonathan C and Lefebvre, Daniel R and Yoon, Michael K}
}
@article {504106,
	title = {AAV-mediated RLBP1 gene therapy improves the rate of dark adaptation in Rlbp1 knockout mice.},
	journal = {Mol Ther Methods Clin Dev},
	volume = {2},
	year = {2015},
	month = {2015},
	pages = {15022},
	abstract = {Recessive mutations in RLBP1 cause a form of retinitis pigmentosa in which the retina, before its degeneration leads to blindness, abnormally slowly recovers sensitivity after exposure to light. To develop a potential gene therapy for this condition, we tested multiple recombinant adeno-associated vectors (rAAVs) composed of different promoters, capsid serotypes, and genome conformations. We generated rAAVs in which sequences from the promoters of the human RLBP1, RPE65, or BEST1 genes drove the expression of a reporter gene (green fluorescent protein). A promoter derived from the RLBP1 gene mediated expression in the retinal pigment epithelium and M{\"u}ller cells (the intended target cell types) at qualitatively higher levels than in other retinal cell types in wild-type mice and monkeys. With this promoter upstream of the coding sequence of the human RLBP1 gene, we compared the potencies of vectors with an AAV2 versus an AAV8 capsid in transducing mouse retinas, and we compared vectors with a self-complementary versus a single-stranded genome. The optimal vector (scAAV8-pRLBP1-hRLBP1) had serotype 8 capsid and a self-complementary genome. Subretinal injection of scAAV8-pRLBP1-hRLBP1 in Rlbp1 nullizygous mice improved the rate of dark adaptation based on scotopic (rod-plus-cone) and photopic (cone) electroretinograms (ERGs). The effect was still present after 1 year.},
	issn = {2329-0501},
	doi = {10.1038/mtm.2015.22},
	author = {Choi, Vivian W and Bigelow, Chad E and McGee, Terri L and Gujar, Akshata N and Li, Hui and Hanks, Shawn M and Vrouvlianis, Joanna and Maker, Michael and Leehy, Barrett and Zhang, Yiqin and Aranda, Jorge and Bounoutas, George and Demirs, John T and Yang, Junzheng and Ornberg, Richard and Wang, Yu and Martin, Wendy and Stout, Kelly R and Argentieri, Gregory and Grosenstein, Paul and Diaz, Danielle and Turner, Oliver and Jaffee, Bruce D and Police, Seshidhar R and Dryja, Thaddeus P}
}
@article {1559546,
	title = {Predicting Global Test-Retest Variability of Visual Fields in Glaucoma},
	journal = {Ophthalmol Glaucoma},
	volume = {4},
	number = {4},
	year = {2021},
	month = {2021 Jul-Aug},
	pages = {390-399},
	abstract = {PURPOSE: To model the global test-retest variability of visual fields (VFs) in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Test-retest VFs from 4044 eyes of 4044 participants. METHODS: We selected 2 reliable VFs per eye measured with the Humphrey Field Analyzer (Swedish interactive threshold algorithm 24-2) within 30 days of each other. Each VF had fixation losses (FLs) of 33\% or less, false-negative results (FNRs) of 20\% or less, and false-positive results (FPRs) of 20\% or less. Stepwise linear regression was applied to select the model best predicting the global test-retest variability from 3 categories of features of the first VF: (1) base parameters (age, mean deviation, pattern standard deviation, glaucoma hemifield test results, FPR, FNR, and FL); (2) total deviation (TD) at each location; and (3) computationally derived archetype VF loss patterns. The global test-retest variability was defined as root mean square deviation (RMSD) of TD values at all 52 VF locations. MAIN OUTCOME MEASURES: Archetype models to predict the global test-retest variability. RESULTS: The mean {\textpm} standard deviation of the root mean square deviation was 4.39 {\textpm} 2.55 dB. Between the 2 VF tests, TD values were correlated more strongly in central than in peripheral VF locations (intraclass coefficient, 0.66-0.89; P \&lt; 0.001). Compared with the model using base parameters alone (adjusted R2\&nbsp;= 0.45), adding TD values improved prediction accuracy of the global variability (adjusted R2\&nbsp;= 0.53; P \&lt; 0.001; Bayesian information criterion [BIC] decrease of 527; change of \&gt;6 represents strong improvement). Lower TD sensitivity in the outermost peripheral VF locations was predictive of higher global variability. Adding archetypes to the base model improved model performance with an adjusted R2 of 0.53 (P \&lt; 0.001) and lowering of BIC by 583. Greater variability was associated with concentric peripheral defect, temporal hemianopia, inferotemporal defect, near total loss, superior peripheral defect, and central scotoma (listed in order of decreasing statistical significance), and less normal VF results and superior paracentral defect. CONCLUSIONS: Inclusion of archetype VF loss patterns and TD values based on first VF improved the prediction of the global test-retest variability than using traditional global VF indices alone.},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2020.12.001},
	author = {Choi, Eun Young and Li, Dian and Fan, Yuying and Pasquale, Louis R and Shen, Lucy Q and Boland, Michael V and Ramulu, Pradeep and Yousefi, Siamak and De Moraes, Carlos Gustavo and Wellik, Sarah R and Myers, Jonathan S and Bex, Peter J and Tobias Elze and Wang, Mengyu}
}
@article {1043216,
	title = {An Unusual Corneal Degeneration},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {6},
	year = {2017},
	month = {2017 Jun 01},
	pages = {667-668},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.5163},
	author = {Choi, Catherine J and Peggy Chang, Han-Ying and Lee, Nahyoung Grace}
}
@article {1295857,
	title = {Single-Cell Dissociation and Characterization in the Murine Retina and Optic Nerve},
	journal = {Methods Mol Biol},
	volume = {1695},
	year = {2018},
	month = {2018},
	pages = {311-334},
	abstract = {Recent technological advances have extended the range of analytic tools to very small samples. It is now possible to assay the transcriptome, and in some cases even the proteome, of single cells reliably. This allows addressing novel questions, such as the genotype/phenotype relationships of single neurons, heterogeneity within individual cells of the same type, or the basis of differential vulnerability to injury. An important prerequisite for these kinds of studies is the ability to isolate well-defined individual cells without contamination by adjacent tissue. In the retina and optic nerve, cells of different types and functions are closely intermingled, limiting the use of standard methods such as laser capture microdissection. Here, we describe a simple method to isolate morphologically intact cells from the retina and the optic nerve and discuss considerations in recognizing and isolating different cell types after dissociation.},
	issn = {1940-6029},
	doi = {10.1007/978-1-4939-7407-8_21},
	author = {Choi, Hee Joo and Wang, Rui and Jakobs, Tatjana C}
}
@article {503911,
	title = {Astrocytes in the optic nerve head express putative mechanosensitive channels.},
	journal = {Mol Vis},
	volume = {21},
	year = {2015},
	month = {2015},
	pages = {749-66},
	abstract = {PURPOSE: To establish whether optic nerve head astrocytes express candidate molecules to sense tissue stretch. METHODS: We used conventional PCR, quantitative PCR, and single-cell reverse transcription PCR (RT-PCR) to assess the expression of various members of the transient receptor potential (TRP) channel family and of the recently characterized mechanosensitive channels Piezo1 and 2 in optic nerve head tissue and in single, isolated astrocytes. RESULTS: Most TRP subfamilies (TRPC, TRPM, TRPV, TRPA, and TRPP) and Piezo1 and 2 were expressed in the optic nerve head of the mouse. Quantitative real-time PCR analysis showed that TRPC1, TRPM7, TRPV2, TRPP2, and Piezo1 are the dominant isoforms in each subfamily. Single-cell RT-PCR revealed that many TRP isoforms, TRPC1-2, TRPC6, TRPV2, TRPV4, TRPM2, TRPM4, TRPM6-7, TRPP1-2, and Piezo1-2, are expressed in astrocytes of the optic nerve head, and that most astrocytes express TRPC1 and TRPP1-2. Comparisons of the TRPP and Piezo expression levels between different tissue regions showed that Piezo2 expression was higher in the optic nerve head and the optic nerve proper than in the brain and the corpus callosum. TRPP2 also showed higher expression in the optic nerve head. CONCLUSIONS: Astrocytes in the optic nerve head express multiple putative mechanosensitive channels, in particular the recently identified channels Piezo1 and 2. The expression of putative mechanosensitive channels in these cells may contribute to their responsiveness to traumatic or glaucomatous injury.},
	issn = {1090-0535},
	author = {Choi, Hee Joo and Sun, Daniel and Jakobs, Tatjana C}
}
@article {634996,
	title = {Nonlimbal Squamous Cell Carcinoma of the Conjunctiva.},
	journal = {Ophthalmology},
	volume = {123},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {254},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.11.006},
	author = {Choi, Catherine J and Stagner, Anna M and Jakobiec, Frederick A and Lee, Nahyoung Grace}
}
@article {468961,
	title = {Isolation of intact astrocytes from the optic nerve head of adult mice.},
	journal = {Exp Eye Res},
	volume = {137},
	year = {2015},
	month = {2015 Aug},
	pages = {103-10},
	abstract = {The astrocytes of the optic nerve head are a specialized subtype of white matter astrocytes that form the direct cellular environment of the unmyelinated ganglion cell axons. Due to their potential involvement in glaucoma, these astrocytes have become a target of research. Due to the heterogeneity of the optic nerve tissue, which also contains other cell types, in some cases it may be desirable to conduct gene expression studies on small numbers of well-characterized astrocytes or even individual cells. Here, we describe a simple method to isolate individual astrocytes. This method permits obtaining astrocytes with intact morphology from the adult mouse optic nerve and reduces contamination of the isolated astrocytes by other cell types. Individual astrocytes can be recognized by their morphology and collected under microscopic control. The whole procedure can be completed in 2-3\&nbsp;h. We also discuss downstream applications like multiplex single-cell PCR and quantitative PCR (qPCR).},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2015.06.014},
	author = {Choi, Hee Joo and Sun, Daniel and Jakobs, Tatjana C}
}
@article {836781,
	title = {Atypical location of primary orbital conjunctival epithelial cysts: a case series.},
	journal = {Clin Experiment Ophthalmol},
	volume = {44},
	number = {6},
	year = {2016},
	month = {2016 Aug},
	pages = {524-6},
	issn = {1442-9071},
	doi = {10.1111/ceo.12693},
	author = {Choi, Catherine J and Stagner, Anna M and Freitag, Suzanne K and Jakobiec, Frederick A and Lee, Nahyoung Grace}
}
@article {1154921,
	title = {Ocular Surface Squamous Neoplasia in a Patient With Hepatitis C},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {10},
	year = {2017},
	month = {2017 Oct 01},
	pages = {1121-1123},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.2967},
	author = {Choi, Catherine J and Jakobiec, Frederick A and Zakka, Fouad R and Sanchez, Angie V and Lee, Nahyoung Grace}
}
@article {680396,
	title = {Validation of the facial assessment by computer evaluation (FACE) program for software-aided eyelid measurements.},
	journal = {Orbit},
	volume = {35},
	number = {3},
	year = {2016},
	month = {2016 Jun},
	pages = {117-20},
	abstract = {The aim of this article is to validate the accuracy of Facial Assessment by Computer Evaluation (FACE) program in eyelid measurements. Sixteen subjects between the ages of 27 and 65 were included with IRB approval. Clinical measurements of upper eyelid margin reflex distance (MRD1) and inter-palpebral fissure (IPF) were obtained. Photographs were then taken with a digital single lens reflex camera with built-in pop-up flash (dSLR-pop) and a dSLR with lens-mounted ring flash (dSLR-ring) with the cameras upright, rotated 90, 180, and 270 degrees. The images were analyzed using both the FACE and ImageJ software to measure MRD1 and IPF.Thirty-two eyes of sixteen subjects were included. Comparison of clinical measurement of MRD1 and IPF with FACE measurements of photos in upright position showed no statistically significant differences for dSLR-pop (MRD1: p = 0.0912, IPF: p = 0.334) and for dSLR-ring (MRD1: p = 0.105, IPF: p = 0.538). One-to-one comparison of MRD1 and IPF measurements in four positions obtained with FACE versus ImageJ for dSLR-pop showed moderate to substantial agreement for MRD1 (intraclass correlation coefficient = 0.534 upright, 0.731 in 90 degree rotation, 0.627 in 180 degree rotation, 0.477 in 270 degree rotation) and substantial to excellent agreement in IPF (ICC = 0.740, 0.859, 0.849, 0.805). In photos taken with dSLR-ring, there was excellent agreement of all MRD1 (ICC = 0.916, 0.932, 0.845, 0.812) and IPF (ICC = 0.937, 0.938, 0.917, 0.888) values. The FACE program is a valid method for measuring margin reflex distance and inter-palpebral fissure.},
	issn = {1744-5108},
	doi = {10.3109/01676830.2016.1139595},
	author = {Choi, Catherine J and Lefebvre, Daniel R and Yoon, Michael K}
}
@article {1470971,
	title = {Clinical implications of recent advances in primary open-angle glaucoma genetics},
	journal = {Eye (Lond)},
	volume = {34},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {29-39},
	abstract = {Over the last decade, genetic studies, including genome-wide association studies (GWAS), have accelerated the discovery of genes and genomic regions contributing to primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss. Here, we review the findings of genetic studies of POAG published in English prior to September 2019. In total, 74 genomic regions have been associated at a genome-wide level of significance with POAG susceptibility. Recent POAG GWAS provide not only insight into global and ethnic-specific genetic risk factors for POAG susceptibility across populations of diverse ancestry, but also important functional insights underlying biological mechanisms of glaucoma pathogenesis. In this review, we also summarize the genetic overlap between POAG, glaucoma endophenotypes, such as intraocular pressure and vertical cup-disc ratio\&nbsp;(VCDR), and other eye disorders. We also discuss approaches recently developed to increase power for POAG locus discovery and to predict POAG risk. Finally, we discuss the recent development of POAG gene-based therapies and future strategies to treat glaucoma effectively. Understanding the genetic architecture of POAG is essential for an earlier diagnosis of this common eye disorder, predictive testing of at-risk patients, and design of gene-based targeted medical therapies none of which are currently available.},
	issn = {1476-5454},
	doi = {10.1038/s41433-019-0632-7},
	author = {Choquet, H{\'e}l{\`e}ne and Wiggs, Janey L and Khawaja, Anthony P}
}
@article {1661608,
	title = {Disparities in Inherited Retinal Degenerations},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {201-206},
	abstract = {To review disparities in the field of inherited retinal degenerations to establish foundations for future discussions oriented toward finding possible solutions. A narrative overview of the literature. Despite collective efforts towards democratization of genetic testing and investigation, genetic databases containing primarily European populations are heavily relied upon. Access to specialized care and other resources is also still not available to all. Recognizing and addressing disparities and inequities within the field of inherited retinal degenerations will improve our care of these patients and our knowledge of their conditions.},
	keywords = {Forecasting, Humans, Retinal Degeneration},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152715},
	author = {Chorfi, Sarah and Place, Emily M and Huckfeldt, Rachel M}
}
@article {1814401,
	title = {Retinal Manifestations in Spinocerebellar Ataxia Type 3},
	journal = {J Neuroophthalmol},
	volume = {44},
	number = {1},
	year = {2024},
	month = {2024 Mar 01},
	pages = {e3-e5},
	keywords = {Brain, Humans, Machado-Joseph Disease, Retina, Spinocerebellar Ataxias},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001759},
	author = {Chorfi, Sarah and Place, Emily M and M Mallery, Robert and Huckfeldt, Rachel M}
}
@article {1195251,
	title = {Reply},
	journal = {Retina},
	volume = {37},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {e118},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001838},
	author = {Chou, Jonathan and Daly, Mary K}
}
@article {1195286,
	title = {CONSTRUCT AND FACE VALIDITY OF THE EYESI INDIRECT OPHTHALMOSCOPE SIMULATOR},
	journal = {Retina},
	volume = {37},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {1967-1976},
	abstract = {PURPOSE: To evaluate construct and face validity of the Eyesi Binocular Indirect Ophthalmoscope Simulator. METHODS: The performance of 25 medical students (Group A) was compared with that of 17 ophthalmology and optometry trainees (Group B) on the Eyesi Binocular Indirect Ophthalmoscope Simulator. During the course of a single session, each participant viewed an orientation module followed by an instruction session and a demonstration case, and performed 6 cases of progressively increasing difficulty (4 levels) and a 10-question face validity questionnaire. Outcomes included total score, total examination time, percent retina examined, and duration of eye exposure to light. RESULTS: Group B achieved significantly better total scores than Group A on all difficulty levels (P = 0.02, P = 0.001, P = 0.001, and P = 0.0001, for Levels 1-4, respectively) and had a significantly faster mean duration of examination (8 minutes 58 seconds vs. 5 minutes 21 seconds, P \&lt; 0.0001). Medical students reported higher scores in the face validity questionnaire for the simulator experience being helpful at orienting them to true indirect ophthalmology, and that further training on the simulator would improve their skills in the clinic (P = 0.03 for all). CONCLUSION: The Eyesi Binocular Indirect Ophthalmoscope Simulator has significant construct and face validity and shows promise for medical education.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001438},
	author = {Chou, Jonathan and Kosowsky, Tova and Payal, Abhishek R and Gonzalez Gonzalez, Luis A and Daly, Mary K}
}
@article {1295858,
	title = {Fundus Densitometry Findings Suggest Optic Disc Hemorrhages in Primary Open-Angle Glaucoma Have an Arterial Origin},
	journal = {Am J Ophthalmol},
	volume = {187},
	year = {2018},
	month = {2018 Mar},
	pages = {108-116},
	abstract = {PURPOSE: To analyze optic disc hemorrhages (DH) associated with primary open-angle glaucoma by quantifying their geometric profile and comparing their densitometry with hemorrhages from retinal vein occlusions (RVO) and retinal macroaneurysms (MA), which have venous and arterial sources of bleeding, respectively. DESIGN: Retrospective cross-sectional study. METHODS: Setting: Massachusetts Eye \&amp; Ear. POPULATION: Fundus images of DH (n\&nbsp;= 40), MA (n\&nbsp;=\&nbsp;14), and RVO (n\&nbsp;= 25) were identified. Patient clinical backgrounds and demographics were obtained. MAIN OUTCOME MEASURES: Grayscale pixel intensity units of hemorrhages and adjacent arteriole and venule over the same background tissue were measured. Densitometry differentials (arteriole or venule minus hemorrhage [ΔA and ΔV, respectively]) were calculated. The ratios of length (radial) to midpoint width for DH were calculated. Mean ΔA and ΔV between groups were compared with t tests. Multiple linear regression assessed the relation of retinal hemorrhage diagnosis to ΔA and ΔV and of DH shape to ΔA and ΔV. RESULTS: Mean ({\textpm} standard deviation) ΔA and ΔV for DH (6.9 {\textpm} 7.1 and\&nbsp;-4.7 {\textpm} 8.0 pixel intensity units, respectively) and MA (5.3 {\textpm} 5.9 and\&nbsp;-6.0 {\textpm} 4.6, respectively) were comparable (P >= .43). Mean ΔA (14.6 {\textpm} 7.7) and ΔV (6.4 {\textpm} 6.3) for RVO were significantly higher compared to DH and MA (P \&lt; .0001) and remained significant in multivariable analyses. A unit increase in DH length-to-width ratio was associated with 1.2 (0.5) and 1.3 (0.5) pixel intensity unit (standard error) decrease in ΔA and ΔV, respectively (P <= .014). CONCLUSIONS: DH have densitometry profiles comparable to MA and different from RVO, suggesting that DH in glaucoma have an arterial origin.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.12.024},
	author = {Chou, Jonathan C and Cousins, Clara C and Miller, John B and Song, Brian J and Shen, Lucy Q and Kass, Michael A and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1655726,
	title = {Clinical Neuroimaging of Photophobia in Individuals With Chronic Ocular Surface Pain},
	journal = {Am J Ophthalmol},
	volume = {246},
	year = {2023},
	month = {2023 Feb},
	pages = {20-30},
	abstract = {PURPOSE: To examine neural mechanisms underlying photophobia in individuals with chronic ocular surface pain by using functional magnetic resonance imaging (fMRI). DESIGN: Cross-sectional case/control analysis. METHODS: A total of 16 individuals from the Miami Veterans Affairs eye clinic underwent comprehensive ocular surface evaluations and were surveyed for ocular surface symptoms. Case patients included patients who reported chronic ocular surface pain symptoms and light sensitivity at least most of the time over 1 week. Controls included persons without chronic ocular surface pain who reported no or minimal light sensitivity. All patients viewed light stimuli during 2 fMRI scans, one before and one after topical anesthetic instillation, and rated their level of pain intensity to the stimulus at the end of each scan. Areas of brain activation in response to light stimuli presentation were correlated with pain responses and examined post- vs pre-anesthesia. RESULTS: Case patients (n\&nbsp;=\&nbsp;8) reported higher pain intensity ratings than controls (n\&nbsp;=\&nbsp;8) in response to light stimuli during fMRI. Case patient ratings correlated more with light-evoked activation in pain-related areas within the trigeminal brainstem, primary somatosensory cortex (S1), anterior mid-cingulate cortex (aMCC), and insula than in controls. Topical anesthesia led to varying responses in pain ratings among case patients as well as decreased light-evoked activation in S1 and aMCC. CONCLUSIONS: The trigeminal nociceptive system may contribute to photophobia in individuals with chronic ocular surface pain. We demonstrate modulation of cortical structures in this pathway with topically applied anesthetic to the eyes. Further understanding of modulatory interactions that govern ocular surface pain and photophobia is critical for developing effective, precision-based therapies.},
	keywords = {Cross-Sectional Studies, Eye Pain, Humans, Magnetic Resonance Imaging, Neuroimaging, Pain, Photophobia},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.09.020},
	author = {Choudhury, Anjalee and Reyes, Nicholas and Galor, Anat and Mehra, Divy and Felix, Elizabeth and Moulton, Eric A}
}
@article {1424800,
	title = {A conjunctival-sparing surgical technique for lower eyelid cicatricial entropion repair in ocular cicatricial pemphigoid},
	journal = {Orbit},
	volume = {39},
	number = {1},
	year = {2020},
	month = {2020 Feb},
	pages = {23-30},
	abstract = {: To present five cases of lower eyelid cicatricial entropion secondary to ocular cicatricial pemphigoid (OCP) successfully repaired with a conjunctival-sparing surgical technique.: The records of one surgeon (SKF) were reviewed to identify patients with lower eyelid cicatricial entropion secondary to OCP who underwent repair with a conjunctival-sparing technique between September 1, 2016 and October 18, 2017. The medical records were reviewed and extracted data included: age, gender, past medical history, current medical and OCP status, clinical examination, details of entropion repair surgery, and outcome.: Five patients (three female, two male) were included with ages ranging from 44 to 93\&nbsp;years. All had biopsy proven OCP, which was in remission at the time of surgery, and all were currently receiving immunomodulatory medications. All patients were symptomatic from cicatricial entropion secondary to OCP and underwent successful lower eyelid entropion repair with a conjunctival-sparing technique described herein, involving infraciliary rotation with suture fixation of the orbicularis muscle to the tarsus. Other contributing mechanisms of eyelid malposition including horizontal eyelid laxity and orbicularis oculi override were addressed simultaneously with lateral tarsal plication or orbicularis muscle debulking, resulting in 100\% anatomic success and relief of symptoms with no cases of OCP reactivation, and with good durability with an average 13.9\&nbsp;months follow up (range 6.5-22\&nbsp;months).: Successful repair of lower eyelid cicatricial entropion in immunomodulated patients with OCP can be achieved without disease reactivation using a surgical technique that spares the conjunctiva and lower eyelid retractors.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2019.1573434},
	author = {Choung, Hokyung and Reshef, Edith R and Tanking, Thidarat and Freitag, Suzanne K}
}
@article {1328878,
	title = {Superonasal Cystic Orbital Mass},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {10},
	year = {2018},
	month = {2018 Oct 01},
	pages = {1203-1204},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.0711},
	author = {Choung, Hokyung and Freitag, Suzanne K and Wolkow, Natalie}
}
@article {1645475,
	title = {Efficacy of Marine ω-3 Fatty Acid Supplementation vs Placebo in Reducing Incidence of Dry Eye Disease in Healthy US Adults: A Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {7},
	year = {2022},
	month = {2022 07 01},
	pages = {707-714},
	abstract = {Importance: Results of several small randomized clinical trials have suggested that supplements of marine ω-3 fatty acids may be beneficial in treating signs and symptoms of dry eye disease (DED). However, randomized clinical trial data to examine whether ω-3 fatty acid supplements can prevent DED are lacking. Objective: To evaluate whether long-term daily supplementation with marine ω-3 fatty acids prevents the development of DED. Design, Setting, and Participants: This was a prespecified ancillary study of the Vitamin D and Omega-3 Trial (VITAL), a nationwide randomized double-blind placebo-controlled 2 {\texttimes} 2 factorial trial of vitamin D and marine ω-3 fatty acids in the primary prevention of cancer and cardiovascular disease. Participants in this ancillary study were 23 523 US adults (men 50 years and older and women 55 years and older) who at study entry were free of a previous diagnosis of DED and were not experiencing severe dry eye symptoms. Participants were enrolled from November 2011 to March 2014, and treatment and follow-up ended on December 31, 2017. Data were analyzed from January 2020 to August 2021. Interventions: Marine ω-3 fatty acids, 1 g per day. Main Outcomes and Measures: The primary end point was incident clinically diagnosed DED confirmed by review of the medical records. The secondary end point was a composite of all confirmed incident clinically diagnosed DED cases plus all incident reports of severe DED symptoms. Results: The mean (SD) age of the 23 523 participants included in the analysis was 67.0 (7.0) years, and 11 349 participants (48.3\%) were women. The cohort included 4610 participants (20.0\%) who self-identified as Black, 16 481 (71.6\%) who self-identified as non-Hispanic White, and 1927 (8.4\%) of other racial or ethnic groups or who declined to respond, consolidated owing to small numbers, including American Indian or Alaska Native, Asian, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander. During a median (range) 5.3 (3.8-6.1) years of treatment and follow-up, 472 of 23 523 participants (2.0\%) experienced a medical record-confirmed diagnosis of DED. There was no difference in diagnosed DED by randomized ω-3 fatty acid assignment (232 of 11 757 participants [2.0\%] with end points in the treated group vs 240 of 11 766 [2.0\%] with end points in the placebo group; hazard ratio, 0.97; 95\% CI, 0.81-1.16). Similarly, there was no difference between groups for the secondary end point of diagnosed DED plus incident severe DED symptoms (1044 participants [8.9\%] with end points in the treated group vs 1074 [9.1\%] with end points in the placebo group; hazard ratio, 0.97; 95\% CI, 0.89-1.06). Conclusions and Relevance: In this randomized clinical trial, long-term supplementation with 1 g per day of marine ω-3 fatty acids for a median (range) of 5.3 (3.8-6.1) years did not reduce the incidence of diagnosed DED or a combined end point of diagnosed DED or incident severe DED symptoms. These results do not support recommending marine ω-3 fatty acid supplementation to reduce the incidence of DED. Trial Registration: ClinicalTrials.gov Identifier: NCT01880463.},
	keywords = {Adult, Aged, Dietary Supplements, Double-Blind Method, Dry Eye Syndromes, Fatty Acids, Omega-3, Female, Humans, Incidence, Male, Vitamin D, Vitamins},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.1818},
	author = {Christen, William G and Cook, Nancy R and Manson, JoAnn E and Buring, Julie E and Lee, I-Min and Bubes, Vadim and Friedenberg, Georgina and Dushkes, Rimma and Smith, Douglas and Schaumberg, Debra A and VITAL Research Group}
}
@article {1688251,
	title = {Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury},
	journal = {Antioxidants (Basel)},
	volume = {12},
	number = {4},
	year = {2023},
	month = {2023 Apr 01},
	abstract = {Ischemia-reperfusion (I/R) events are involved in the development of various ocular pathologies, e.g., retinal artery or vein occlusion. We tested the hypothesis that resveratrol is protective against I/R injury in the murine retina. Intraocular pressure (IOP) was elevated in anaesthetized mice to 110 mm Hg for 45 min via a micropipette placed in the anterior chamber to induce ocular ischemia. In the fellow eye, which served as control, IOP was kept at a physiological level. One group received resveratrol (30 mg/kg/day p.o. once daily) starting one day before the I/R event, whereas the other group of mice received vehicle solution only. On day eight after the I/R event, mice were sacrificed and retinal wholemounts were prepared and immuno-stained using a Brn3a antibody to quantify retinal ganglion cells. Reactivity of retinal arterioles was measured in retinal vascular preparations using video microscopy. Reactive oxygen species (ROS) and nitrogen species (RNS) were quantified in ocular cryosections by dihydroethidium and anti-3-nitrotyrosine staining, respectively. Moreover, hypoxic, redox and nitric oxide synthase gene expression was quantified in retinal explants by PCR. I/R significantly diminished retinal ganglion cell number in vehicle-treated mice. Conversely, only a negligible reduction in retinal ganglion cell number was observed in resveratrol-treated mice following I/R. Endothelial function and autoregulation were markedly reduced, which was accompanied by increased ROS and RNS in retinal blood vessels of vehicle-exposed mice following I/R, whereas resveratrol preserved vascular endothelial function and autoregulation and blunted ROS and RNS formation. Moreover, resveratrol reduced I/R-induced mRNA expression for the prooxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2). Our data provide evidence that resveratrol protects from I/R-induced retinal ganglion cell loss and endothelial dysfunction in the murine retina by reducing nitro-oxidative stress possibly via suppression of NOX2 upregulation.},
	issn = {2076-3921},
	doi = {10.3390/antiox12040853},
	author = {Chronopoulos, Panagiotis and Manicam, Caroline and Zadeh, Jenia Kouchek and Laspas, Panagiotis and Unkrig, Johanna Charlotte and G{\"o}bel, Marie Luise and Musayeva, Aytan and Pfeiffer, Norbert and Oelze, Matthias and Daiber, Andreas and Li, Huige and Xia, Ning and Gericke, Adrian}
}
@article {397786,
	title = {Hyperhexosemia-induced retinal vascular pathology in a novel primate model of diabetic retinopathy.},
	journal = {Diabetes},
	year = {2015},
	month = {2015 Mar 2},
	abstract = {The paucity of animal models exhibiting full pathology of diabetic retinopathy (DR) has impeded understanding of the pathogenesis of DR and the development of therapeutic interventions. Here we investigated if hyperhexosemic marmosets (Callithrix jacchus) develop characteristic retinal vascular lesions including macular edema (ME), a leading cause of vision loss in DR. Marmosets maintained on 30\% galactose (gal)-rich diet for two years were monitored for retinal vascular permeability, development of ME, and morphological characteristics including acellular capillaries (AC) and pericyte loss (PL), vessel tortuosity, and capillary basement membrane (BM) thickness. Excess vascular permeability, increased number of AC and PL, vascular BM thickening, and increased vessel tortuosity were observed in the retinas of gal-fed marmosets. Optical coherence tomography (OCT) images revealed significant thickening of the retinal foveal and the juxtafoveal area, and histological analysis showed incipient microaneurysms in retinas of gal-fed marmosets. Findings from this study indicate that hyperhexosemia can trigger retinal vascular changes similar to those seen in human DR including ME and microaneurysms. The striking similarities between the marmoset retina and the human retina, and the exceptionally small size of the monkey, offer significant advantages to this primate model of DR.},
	issn = {1939-327X},
	doi = {10.2337/db14-0866},
	author = {Chronopoulos, Argyrios and Roy, Sumon and Beglova, Ekaterina and Mansfield, Keith and Wachtman, Lynn and Roy, Sayon}
}
@article {1806516,
	title = {Dual-Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease},
	journal = {Nanomicro Lett},
	volume = {16},
	number = {1},
	year = {2024},
	month = {2024 Feb 19},
	pages = {120},
	abstract = {Dry eye disease (DED) is a major ocular pathology worldwide, causing serious ocular discomfort and even visual impairment. The incidence of DED is gradually increasing with the high-frequency use of electronic products. Although inflammation is core cause of the DED vicious cycle, reactive oxygen species (ROS) play a pivotal role in the vicious cycle by regulating inflammation from upstream. Therefore, current therapies merely targeting inflammation show the failure of DED treatment. Here, a novel dual-atom nanozymes (DAN)-based eye drops are developed. The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer. The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS, inhibiting NLRP3 inflammasome activation, decreasing proinflammatory cytokines expression, and suppressing cell apoptosis. Consequently, the DAN effectively alleviate ocular inflammation, promote corneal epithelial repair, recover goblet cell density and tear secretion, thus breaking the DED vicious cycle. Our findings open an avenue to make the DAN as an intervention form to DED and ROS-mediated inflammatory diseases.},
	issn = {2150-5551},
	doi = {10.1007/s40820-024-01322-7},
	author = {Chu, Dandan and Zhao, Mengyang and Rong, Shi Song and Jhe, Wonho and Cai, Xiaolu and Xiao, Yi and Zhang, Wei and Geng, Xingchen and Li, Zhanrong and Zhang, Xingcai and Li, Jingguo}
}
@article {1709676,
	title = {Tackling prediction uncertainty in machine learning for healthcare},
	journal = {Nat Biomed Eng},
	volume = {7},
	number = {6},
	year = {2023},
	month = {2023 Jun},
	pages = {711-718},
	abstract = {Predictive machine-learning systems often do not convey the degree of confidence in the correctness of their outputs. To prevent unsafe prediction failures from machine-learning models, the users of the systems should be aware of the general accuracy of the model and understand the degree of confidence in each individual prediction. In this Perspective, we convey the need of prediction-uncertainty metrics in healthcare applications, with a focus on radiology. We outline the sources of prediction uncertainty, discuss how to implement prediction-uncertainty metrics in applications that require zero tolerance to errors and in applications that are error-tolerant, and provide a concise framework for understanding prediction uncertainty in healthcare contexts. For machine-learning-enabled automation to substantially impact healthcare, machine-learning models with zero tolerance for false-positive or false-negative errors must be developed intentionally.},
	keywords = {machine learning, Uncertainty},
	issn = {2157-846X},
	doi = {10.1038/s41551-022-00988-x},
	author = {Chua, Michelle and Kim, Doyun and Choi, Jongmun and Lee, Nahyoung G and Deshpande, Vikram and Schwab, Joseph and Lev, Michael H and Gonzalez, Ramon G and Gee, Michael S and Do, Synho}
}
@article {1263311,
	title = {Refractive Errors \&amp; Refractive Surgery Preferred Practice Pattern{\textregistered}},
	journal = {Ophthalmology},
	volume = {125},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {P1-P104},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.10.003},
	author = {Chuck, Roy S and Jacobs, Deborah S and Lee, Jimmy K and Afshari, Natalie A and Vitale, Susan and Shen, Tueng T and Keenan, Jeremy D and American Academy of Ophthalmology Preferred Practice Pattern Refractive Management/Intervention Panel}
}
@article {1364595,
	title = {Refractive Development in the "ROP Rat"},
	journal = {J Ophthalmol},
	volume = {2012},
	year = {2012},
	month = {2012},
	pages = {956705},
	abstract = {Although retinopathy of prematurity (ROP) is clinically characterized by abnormal retinal vessels at the posterior pole of the eye, it is also commonly characterized by vascular abnormalities in the anterior segment, visual dysfunction which is based in retinal dysfunction, and, most commonly of all, arrested eye growth and high refractive error, particularly (and paradoxically) myopia. The oxygen-induced retinopathy rat model of ROP presents neurovascular outcomes similar to the human disease, although it is not yet known if the "ROP rat" also models the small-eyed myopia characteristic of ROP. In this study, magnetic resonance images (MRIs) of albino (Sprague-Dawley) and pigmented (Long-Evans) ROP rat eyes, and age- and strain-matched room-air-reared (RAR) controls, were examined. The positions and curvatures of the various optical media were measured and the refractive state (℞) of each eye estimated based on a previously published model. Even in adulthood (postnatal day 50), Sprague-Dawley and Long-Evans ROP rats were significantly myopic compared to strain-matched controls. The myopia in the Long-Evans ROP rats was more severe than in the Sprague-Dawley ROP rats, which also had significantly shorter axial lengths. These data reveal the ROP rat to be a novel and potentially informative approach to investigating physiological mechanisms in myopia in general and the myopia peculiar to ROP in particular.},
	issn = {2090-0058},
	doi = {10.1155/2012/956705},
	author = {Chui, Toco Y P and Bissig, David and Berkowitz, Bruce A and Akula, James D}
}
@article {882901,
	title = {Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation.},
	journal = {Curr Opin Ophthalmol},
	year = {2016},
	month = {2016 Aug 31},
	abstract = {PURPOSE OF REVIEW: Review recent advances in clinical and experimental studies of dominant optic atrophy (DOA) to better understand the complexities of pathophysiology caused by the optic atrophy 1 (OPA1) mutation. RECENT FINDINGS: DOA is the most commonly diagnosed inherited optic atrophy, causing progressive bilateral visual loss that begins early in life. During the past 25 years, there has been substantial progress in the understanding of the clinical, genetic, and pathophysiological basis of this disease. The histopathological hallmark of DOA is the primary degeneration of retinal ganglion cells, preferentially in the papillomacular bundle, which results temporal optic disc pallor and cecocentral scotomata in patients with DOA. Loss of OPA1 protein function by OPA1 gene mutations causes mitochondrial dysfunction because of the loss of mitochondrial fusion, impaired mitochondrial oxidative phosphorylation, increases in reactive oxygen species, and altered calcium homeostasis. These factors lead to apoptosis of retinal ganglion cells by a haploinsufficiency mechanism. SUMMARY: Improved understanding of the pathophysiology of DOA provides insights that can be used to develop therapeutic approaches to the DOA.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000314},
	author = {Chun, Bo Y and Rizzo, Joseph F}
}
@article {1137871,
	title = {Advances in experimental optic nerve regeneration},
	journal = {Curr Opin Ophthalmol},
	volume = {28},
	number = {6},
	year = {2017},
	month = {2017 Nov},
	pages = {558-563},
	abstract = {PURPOSE OF REVIEW: Recent advances in experimental studies of optic nerve regeneration to better understand the pathophysiology of axon regrowth and provide insights into the future treatment of numerous optic neuropathies. RECENT FINDINGS: The optic nerve is part of the central nervous system and cannot regenerate if injured. There are several steps that regenerating axons of retinal ganglion cells (RGCs) must take following optic nerve injury that include: maximizing the intrinsic growth capacity of RGCs, overcoming the extrinsic growth-inhibitory environment of the optic nerve, and optimizing the reinnervation of regenerated axons to their targets in the brain. Recently, some degree of experimental optic nerve regeneration has been achieved by factors associated with inducing intraocular inflammation, providing exogenous neurotrophic factors, reactivating intrinsic growth capacity of mature RGCs, or by modifying the extrinsic growth-inhibitory environment of the optic nerve. In some experiments, regenerating axons have been shown to reinnervate their central targets in the brain. SUMMARY: Further approaches to the combination of aforementioned treatments will be necessary to develop future therapeutic strategy to promote ultimate regeneration of the optic nerve and functional vision recovery after optic nerve injury.},
	keywords = {Animals, Axons, Disease Models, Animal, Humans, Nerve Regeneration, Optic Nerve, Optic Nerve Injuries, Retinal Ganglion Cells},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000417},
	author = {Chun, Bo Young and Cestari, Dean M}
}
@article {1359921,
	title = {Myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis},
	journal = {Curr Opin Ophthalmol},
	volume = {29},
	number = {6},
	year = {2018},
	month = {2018 Nov},
	pages = {508-513},
	abstract = {PURPOSE OF REVIEW: Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated optic neuritis has been established as a new entity of optic neuropathy. We will review recent advances in pathophysiology, diagnosis, and clinical manifestations of MOG-IgG-associated optic neuritis to better understand its distinctive characteristics. RECENT FINDINGS: MOG is expressed on the surface of myelin sheaths and oligodendrocytes. MOG is highly immunogenic and is a potential target of inflammatory demyelinating disease. MOG-IgG activate immune responses and cause demyelination without astrocytopathy. MOG-IgG are measured by cell-based assays, which have higher sensitivity and specificity than ELISA. Patients with MOG-IgG-associated optic neuritis present with initially severe vision loss, are more likely to have optic disc edema, but have favorable visual outcomes. Furthermore, patients with MOG-IgG-associated optic neuritis have higher rates of recurrence compared with MOG-IgG seronegative patients. MOG-IgG-associated optic neuritis responds well to steroid treatment, however, close monitoring for signs of relapse and long-term immunosuppression may be necessary. SUMMARY: MOG-IgG associated optic neuritis demonstrates distinctive pathophysiological and clinical characteristics from optic neuritis in aquaporin4-IgG seropositive or multiple sclerosis patients. Measurements of MOG-IgG titers by cell-based assays will be helpful for the diagnosis and treatment of optic neuritis.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000520},
	author = {Chun, Bo Young and Cestari, Dean M}
}
@article {1430524,
	title = {The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene},
	journal = {Am J Ophthalmol},
	volume = {199},
	year = {2019},
	month = {2019 Mar},
	pages = {58-70},
	abstract = {PURPOSE: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. DESIGN: Global, multicenter, retrospective chart review. METHODS: Study Population: Seventy individuals with biallelic RPE65 mutation-associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). RESULTS: VA decreased with age in a nonlinear, positive-acceleration relationship (P \&lt; .001). GVF decreased with age (P \&lt; .0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P\&nbsp;= .0114, left eye; P\&nbsp;= .0076, right eye). On average, a 1-year increase in age decreased III4e GVF by \~{}25 sum total degrees in each eye while V4e GVF decreased by \~{}37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. CONCLUSIONS: The number of clinical diagnoses and lack of a consistent RPE65 mutation-to-phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.09.024},
	author = {Chung, Daniel C and Bertelsen, Mette and Lorenz, Birgit and Pennesi, Mark E and Leroy, Bart P and Hamel, Christian P and Pierce, Eric and Sallum, Juliana and Larsen, Michael and Stieger, Knut and Preising, Markus and Weleber, Richard and Yang, Paul and Place, Emily and Liu, Emily and Schaefer, Grace and DiStefano-Pappas, Julie and Elci, Okan U and McCague, Sarah and Wellman, Jennifer A and High, Katherine A and Reape, Kathleen Z}
}
@article {1359922,
	title = {Neuro-ophthalmic complications of IgG4-related disease},
	journal = {Curr Opin Ophthalmol},
	volume = {29},
	number = {6},
	year = {2018},
	month = {2018 Nov},
	pages = {485-494},
	abstract = {PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is increasingly recognized as a fibroinflammatory disease with a plethora of organ-specific manifestations but a particular predilection for head and neck tissues, including the nervous system. This review discusses general features and organ-specific presentations of IgG4-RD as well as treatment considerations, particularly emphasizing features of neuro-ophthalmic interest. RECENT FINDINGS: IgG4-RD is emerging as a common cause of several fibroinflammatory disorders in the head and neck that were previously considered idiopathic, such as sclerosing orbital pseudotumor, orbital myositis, hypophysitis, and hypertrophic pachymeningitis. New and unusual presentations continue to be described, including a number of vascular manifestations. Substantial progress has been made in elucidating the cell types involved in IgG4-RD, and new pathogenic models are being proposed. Although clinicopathologic correlation remains the cornerstone of diagnosis, ancillary tests such as flow cytometry for circulating plasmablasts and PET-computed tomography have high sensitivity, and certain radiologic features are recognized to be particularly suggestive, such as infraorbital nerve enlargement in IgG4-RD orbitopathy. IgG4-RD often responds to steroids but incomplete responses and relapses are common. Rituximab is emerging as a promising new therapy. SUMMARY: The current review summarizes manifestations of IgG4RD that are of particular relevance to neuro-ophthalmic practice.},
	keywords = {Autoimmune Diseases, Autoimmune Hypophysitis, Diagnostic Techniques, Ophthalmological, Flow Cytometry, Humans, Immunoglobulin G, Meningitis, Orbital Myositis, Orbital Pseudotumor, Positron-Emission Tomography, Tomography, X-Ray Computed},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000523},
	author = {Chwalisz, Bart K and Stone, John H}
}
@article {1263316,
	title = {Neuroimaging diagnostic and monitoring approaches in ophthalmology},
	journal = {Curr Opin Neurol},
	volume = {31},
	number = {1},
	year = {2018},
	month = {2018 Feb},
	pages = {66-73},
	abstract = {PURPOSE OF REVIEW: We review new applications of optical coherence tomography (OCT) technology in neuro-ophthalmology. We also describe new technologies for visualizing the extracranial vessels in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Newer OCT modalities are expanding the evaluation of the optic disc, and are being applied to a number of neurologic conditions such as demyelinating and neurodegenerative disease. Swept-source OCT and enhanced-depth imaging OCT are refining the fine-grained analysis of the optic nerve head in the diagnosis of papilledema and optic nerve drusen. OCT-angiography is opening up new avenues to the study of the vasculature of the optic nerve head and its disorders, including ischemic optic neuropathy. Newer technologies in the diagnosis of GCA include vascular ultrasound, magnetic resonance imaging (MRI) of the extracranial vasculature and PET imaging of the large vessels. SUMMARY: OCT and several of its derivations are advancing diagnosis, and in some cases prognostication, in a variety of inflammatory, ischemic and compressive optic neuropathies. These technologies hold potential in the laboratory as well, yielding insights into the mechanisms of a variety of neurological conditions. In addition, further developments in MRI and ultrasonography techniques are shaping the approach to the diagnosis of GCA.},
	issn = {1473-6551},
	doi = {10.1097/WCO.0000000000000518},
	author = {Chwalisz, Bart K and Bouffard, Marc A and Prasad, Sashank and Cestari, Dean M}
}
@article {1653583,
	title = {The Treatment of Myelin Oligodendrocyte Glycoprotein Antibody Disease: A State-of-the-Art Review},
	journal = {J Neuroophthalmol},
	volume = {42},
	number = {3},
	year = {2022},
	month = {2022 Sep 01},
	pages = {292-296},
	abstract = {BACKGROUND: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is an important etiology of neurologic morbidity and specifically, atypical, and relapsing optic neuritis. This review summarizes acute treatment and long-term prevention approaches in MOGAD. EVIDENCE ACQUISITION: PubMed and Google Scholar databases were manually searched and reviewed. RESULTS: We review the evidence base for acute treatment of MOGAD with corticosteroids and adjunct therapies, such as intravenous immunoglobulin (IVIg) and plasma exchange. We discuss the utility of prolonged corticosteroid tapering after the acute attack. We then summarize the commonly used disease-modifying treatments for relapsing MOGAD, including chronic low-dose corticosteroids, classic antirheumatic immune suppressants, biologic agents, and IVIg. CONCLUSIONS: While acute MOGAD attacks are usually treated with high-dose IV corticosteroids, longer oral corticosteroid tapers may prevent rapid relapse. Multiple long-term treatment strategies are being employed in recurrent MOGAD, with IVIg is emerging as probably the most effective therapy.},
	keywords = {Adrenal Cortex Hormones, Aquaporin 4, Autoantibodies, Humans, Immunoglobulins, Intravenous, Myelin-Oligodendrocyte Glycoprotein, Neuromyelitis Optica, Optic Neuritis},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001684},
	author = {Chwalisz, Bart K and Michael Levy}
}
@article {1179151,
	title = {Perioperative Vision Loss after Non-Ocular Surgery},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Sep 07},
	pages = {1-6},
	abstract = {Perioperative vision loss (POVL) may cause devastating visual morbidity. A prompt anatomical and etiologic diagnosis is paramount to guide management and assess prognosis. Where possible, steps should be undertaken to minimize risk of POVL for vulnerable patients undergoing high-risk procedures. We review the specific risk factors, pathophysiology, and management and prevention strategies for various etiologies of POVL.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353807},
	author = {Chwalisz, Bart and Gilbert, Aubrey L and Gittinger, John W}
}
@article {1532367,
	title = {Disease of the Year: COVID-19 and Its Neuro-ophthalmic Complications},
	journal = {J Neuroophthalmol},
	volume = {40},
	number = {3},
	year = {2020},
	month = {2020 09},
	pages = {283-284},
	keywords = {Betacoronavirus, China, Coronavirus, Coronavirus Infections, Humans, Pandemics, Pneumonia, Viral},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001046},
	author = {Chwalisz, Bart K and Dinkin, Marc J}
}
@article {1593845,
	title = {Cerebral amyloid angiopathy and related inflammatory disorders},
	journal = {J Neurol Sci},
	volume = {424},
	year = {2021},
	month = {2021 05 15},
	pages = {117425},
	abstract = {Inflammatory cerebral amyloid angiopathy is a largely reversible inflammatory vasculopathy that develops in an acute or subacute fashion in reaction to amyloid protein deposition in the central nervous system blood vessels. There are two recognized pathologically characterized variants: cerebral amyloid angiopathy-related inflammation (CAAri) and A beta-related angiitis (ABRA). Both variants produce a clinical picture that resembles primary angiitis of the CNS but is distinguished by a characteristic radiologic appearance. Although originally defined as a clinicopathologic diagnosis, it can now often be diagnosed based on clinicoradiologic criteria, though confirmation with brain and meningeal biopsy is still required in some cases. This disorder typically responds to steroids but addition of other immune suppressants may be needed in some cases to control the disease.},
	keywords = {Amyloid beta-Peptides, Brain, Central Nervous System, Cerebral Amyloid Angiopathy, Humans, Meninges, Vasculitis},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2021.117425},
	author = {Chwalisz, B K}
}
@article {1517192,
	title = {Episodic Visual Distortions and Stroke-Like Symptoms in a 56-Year-Old Man With Intravascular Lymphoma},
	journal = {J Neuroophthalmol},
	volume = {40},
	number = {2},
	year = {2020},
	month = {2020 Jun},
	pages = {265-270},
	abstract = {A healthy 56-year-old man presented with vision changes and left upper extremity motor and sensory changes. MRI of the brain without contrast was significant for multifocal areas of restricted diffusion in multiple vascular territories. Neuro-Ophthalmic evaluation revealed an inferonasal visual field defect in the left eye, thickened choroid on optical coherence tomography, and bilateral delayed arteriovenous and choroidal filling on fluorescein angiogram. Repeat MRI demonstrated interval enlargement of many of the same foci of abnormal diffusion-weighted imaging signal. Computed tomography of the abdomen and pelvis revealed 3 distinct lobulated retroperitoneal masses that were biopsied and found to be consistent with diffuse large B-cell lymphoma. Brain biopsy specimens showed intravascular lymphocytes, confirming a diagnosis of intravascular lymphoma (IVL). In this diagnostically challenging case, a link was established between the presence of multiple strokes (some of which showed slow evolution over time) and retinochoroidal hypoperfusion, which provided a critical clue to the ultimate diagnosis of IVL.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000900},
	author = {Chwalisz, Bart K and Douglas, Vivian P and Douglas, Konstantinos Aa and Martinez-Lage, Maria and Kelly, Hilary R and Cestari, Dean M}
}
@article {1814426,
	title = {Racial Disparities in Glaucoma Vision Outcomes and Eye Care Utilization: An IRIS{\textregistered} Registry Analysis},
	journal = {Am J Ophthalmol},
	year = {2024},
	month = {2024 Mar 26},
	abstract = {PURPOSE: To evaluate racial disparities in vision outcomes and eye care utilization among glaucoma patients. DESIGN: Retrospective cohort study. SETTING: Population-based IRIS Registry (Intelligent Research in Sight) study. PARTICIPANTS: Patients with minimum one diagnosis code for glaucoma at least 6 months prior to Jan 1st, 2015 and at least one eye exam, visual field (VF), optical coherence tomography (OCT), or eye-related inpatient or emergency department (ED) code in 2015. MAIN OUTCOMES AND MEASURES: Multivariable logistic and negative binomial regression models were used to assess vision and utilization outcomes, respectively, across race and ethnicity from Jan 1st 2015 - Jan 1st 2020. Vision outcomes included cup-to-disc ratio (CDR) progression \&gt; 0.80, poor vision (visual acuity 20/200 or worse), low vision codes, and need for glaucoma filtering surgery. Utilization outcomes included outpatient eye exams, OCTs, VFs, inpatient/ED encounters, and lasers/surgeries. RESULTS: Among 996,297 patients, 73\% were non-Hispanic White, 15\% non-Hispanic Black, 9\% Hispanic, 3\% Asian/Pacific Islander, and 0.3\% Native American/Alaska Native. Compared to White eyes, Black and Hispanic eyes had higher adjusted odds of CDR progression (odds ratio (OR)=1.12, 95\%CI=1.08-1.17; OR=1.28, 95\%CI=1.22-1.34), poor vision (OR=1.26, 95\%CI=1.22-1.29; OR=1.26, 95\%CI=1.22-1.31), glaucoma filtering surgery (rate ratio (RR)=1.47, 95\%CI=1.42-1.51; RR=1.13, 95\%CI=1.09-1.18). Hispanic eyes also had increased odds of low vision diagnoses (Hispanic OR=1.18, 95\%CI=1.07-1.30). Black and Hispanic patients were less likely to have eye exams (RR=0.94, 95\%CI=0.94-0.95; RR=0.99, 95\%CI=0.99-0.99) and OCTs (RR=0.86, 95\%CI=0.85-0.86; RR=0.97, 95\%CI=0.96-0.98), yet Black patients had higher odds of inpatient/ED encounters (RR=1.64, 95\%CI=1.37-1.96) compared to White patients. Native American patients were more likely to have poor vision (OR=1.17, 95\%CI=1.01-1.36) and less likely to have outpatient visits (RR=0.89, 95\%CI=0.86-0.91), OCTs (RR=0.85, 95\%CI=0.82-0.89), visual fields (RR=0.91, 95\%CI=0.88-0.94) or lasers/surgeries (RR=0.87, 95\%CI=0.79-0.96) compared to White patients. CONCLUSIONS: We found that significant disparities in US eye care exist with Black, Hispanic, and Native American patients having worse vision outcomes and less disease monitoring. Glaucoma may be undertreated in these racial and ethnic minority groups, increasing risk for glaucoma-related vision loss.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2024.03.022},
	author = {Ciociola, Elizabeth C and Sekimitsu, Sayuri and Smith, Sophie and Lorch, Alice C and Miller, Joan W and Tobias Elze and Zebardast, Nazlee}
}
@article {1593848,
	title = {The Heritability of Primary Angle Closure Anatomic Traits and Predictors of Angle Closure in South Indian Siblings},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 May 13},
	abstract = {PURPOSE: To estimate the heritability of ocular biometric and anterior chamber morphologic parameters and to determine predictors of angle closure concordance in South Indian probands with angle closure and their siblings. DESIGN: Prospective observational cohort study. METHODS: Subjects received a standardized ophthalmic examination, A-scan ultrasonography, pachymetry, and anterior segment optical coherence tomography (ASOCT) imaging. Heritability was calculated using residual correlation coefficients adjusted for age, sex, and home setting. Concordant siblings pairs were defined as both proband and sibling with angle closure. Predictors of angle closure concordance among siblings were calculated using multivariable logistic regression models. RESULTS: 345 sibling pairs participated. All anterior chamber parameters were highly heritable (p\&lt;0.001 for all). Similarly, all iris parameters, axial length, lens thickness (LT), central corneal thickness, anterior lens curvature, lens vault (LV), spherical equivalent, and intraocular pressure were moderately to highly heritable (p\&lt;0.004 for all). LV and LT were more heritable among concordant siblings (p\&lt;0.05 for both). In contrast, ASOCT angle parameters had statistically insignificant heritability estimates. In multivariable analyses, siblings older than their probands were more likely to be concordant for angle closure (OR=1.05 (95\% CI 1.01, 1.09), p=0.02) and siblings with deeper anterior chamber depths (ACD) compared to their proband were less likely to be concordant for angle closure (OR=0.74 (95\% CI 0.64, 0.86), p\&lt;0.001). CONCLUSIONS: Iris, anterior chamber, and lens parameters may be heritable while angle parameters were not. LT and LV may play important roles in the pathogenesis of angle closure. Siblings who are older or have a shallower ACD may need more careful disease monitoring.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.04.038},
	author = {Ciociola, Elizabeth C and Kavitha, Srinivasan and Sengupta, Sabyasachi and Wiggs, Janey L and Kader, Mohideen Abdul and Raman, Ganesh V and Rajendrababu, Sharmila and Ramulu, Pradeep Y and Venkatesh, Rengaraj and Zebardast, Nazlee}
}
@article {1647885,
	title = {Effectiveness of Trabeculectomy and Tube Shunt with versus without Concurrent Phacoemulsification: Intelligent Research in Sight Registry Longitudinal Analysis},
	journal = {Ophthalmol Glaucoma},
	volume = {6},
	number = {1},
	year = {2023},
	month = {2023 Jan-Feb},
	pages = {42-53},
	abstract = {OBJECTIVE: To determine the effectiveness of trabeculectomy and glaucoma drainage device (GDD) surgery performed with concurrent phacoemulsification compared with stand-alone procedures. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight Registry who underwent trabeculectomy or GDD from 2013 through\&nbsp;2019. METHODS: The Kaplan-Meier survival analysis was used to determine reoperation rates. Reoperation was defined as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine reoperation risk factors. MAIN OUTCOME MEASURES: Reoperation rate, intraocular pressure (IOP), visual acuity, reoperation procedure type, postoperative complications, and predictors of surgical failure. RESULTS: A total of 117 697 eyes undergoing glaucoma surgery alone and 35 657 eyes undergoing surgery with phacoemulsification were included. The cumulative reoperation rates at postoperative years 1 and 3 were 4.9\% and 11.5\%, respectively, for trabeculectomy alone and 3.0\% and 7.3\%, respectively, for trabeculectomy combined with phacoemulsification (P \&lt; 0.001). The reoperation rates at postoperative 1 and 3 years were 3.8\% and 7.8\%, respectively, for GDD alone and 2.1\% and 5.4\%, respectively, for GDD with phacoemulsification (P \&lt; 0.001). Stand-alone procedures achieved greater IOP reduction by percentage change from baseline (trabeculectomy alone, 35.3\% vs. trabeculectomy with phacoemulsification, 23.1\%, P \&lt; 0.001; and GDD alone, 36.0\% vs. GDD with phacoemulsification, 29.3\%; P \&lt; 0.001). Visual acuity improved by 0.12 logarithm of the minimum angle of resolution (logMAR) (95\% confidence interval [CI], 0.11-0.12) and 0.10 logMAR (95\% CI, 0.08-0.11) after trabeculectomy and GDD with phacoemulsification and declined by 0.15 logMAR (95\% CI, 0.14-0.15) and 0.12 logMAR (95\% CI, 0.11-0.12) after stand-alone trabeculectomy and GDD. The overall documented complication rate was 2.9\% for GDD and 1.4\% for trabeculectomy. Age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical failure risk. The most common reoperation procedure was GDD. CONCLUSIONS: Reoperation rates within the first 3 years after trabeculectomy and GDD with and without phacoemulsification were low. Trabeculectomy and GDD with phacoemulsification had lower reoperation rates than those with stand-alone procedures. However, stand-alone procedures resulted in greater IOP reduction compared with combined procedures. Postoperative complications were uncommon overall. Patient age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical success.},
	keywords = {Glaucoma, Humans, Phacoemulsification, Postoperative Complications, Retrospective Studies, Trabeculectomy},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.07.003},
	author = {Ciociola, Elizabeth C and Yang, Shuang-An and Hall, Nathan and Lorch, Alice C and Miller, Joan W and Friedman, David S and Boland, Michael V and Tobias Elze and Zebardast, Nazlee and IRIS Registry Data Analytic Center Consortium}
}
@article {1363256,
	title = {Retention of the Boston keratoprosthesis type 1: multicenter study results},
	journal = {Ophthalmology},
	volume = {120},
	number = {6},
	year = {2013},
	month = {2013 Jun},
	pages = {1195-200},
	abstract = {OBJECTIVE: To report the retention rate of the Boston keratoprosthesis type 1 and to identify risk factors for keratoprosthesis loss. DESIGN: Cohort study. PARTICIPANTS: A total of 300 eyes of 300 patients who underwent implantation of the Boston keratoprosthesis type I device between January 2003 and July 2008 by 19 surgeons at 18 medical centers. METHODS: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site. MAIN OUTCOME MEASURES: Keratoprosthesis retention. RESULTS: A total cumulative number of 422 life-years of device implantation are included in this analysis. The average duration of follow-up was 17.1 {\textpm} 14.8 months, with a range of 1 week to \&gt;6.1 years. Ninety-three percent of the 300 Boston keratoprosthesis implants were retained at their last follow-up, corresponding to a retention time of 396 patient-years or 1.42 years/keratoprosthesis. The probability of retention after 1 year and 2 years was 94\% and 89\%, respectively. During the study period, 21 (7\%) eyes failed to retain the device; the reasons for keratoprosthesis loss include sterile keratolysis (9), fungal infections (8), dense retroprosthetic membranes (3), and bacterial endophthalmitis (1). Multivariate analysis demonstrated 3 independent risk factors for keratoprosthesis loss: autoimmune cause (hazard ratio [HR], 11.94; 95\% confidence interval [CI], 3.31-43.11), ocular surface exposure requiring a concomitant tarsorrhaphy (HR, 3.43; 95\% CI, 1.05-11.22), and number of prior failed penetrating keratoplasties (HR, 1.64; 95\% CI, 1.18-2.28). CONCLUSIONS: The Boston keratoprosthesis type 1 seems to be a viable option for eyes that are not candidates for penetrating keratoplasty (PK). Ocular surface disease due to an autoimmune cause demonstrated the lowest retention rate. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
	keywords = {Adolescent, Adult, Aged, Artificial Organs, Child, Cohort Studies, Cornea, Corneal Diseases, Corneal Transplantation, Female, Follow-Up Studies, Graft Rejection, Graft Survival, Humans, Intraoperative Complications, Male, Middle Aged, Postoperative Complications, Prospective Studies, Prosthesis Implantation, Risk Factors, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2012.11.025},
	author = {Ciolino, Joseph B and Belin, Michael W and Todani, Amit and Al-Arfaj, Khalid and Rudnisky, Christopher J and Boston Keratoprosthesis Type 1 Study Group}
}
@article {882906,
	title = {Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys.},
	journal = {Ophthalmology},
	volume = {123},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {2085-92},
	abstract = {PURPOSE: To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys. DESIGN: Preclinical efficacy study of 3 treatment arms in a crossover design. PARTICIPANTS: Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty. METHODS: Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis. MAIN OUTCOME MEASURES: Intraocular pressure. RESULTS: Latanoprost ophthalmic solution resulted in IOP reduction of 5.4{\textpm}1.0 mmHg on day 3 and peak IOP reduction of 6.6{\textpm}1.3 mmHg on day 5. The CLLO reduced IOP by 6.3{\textpm}1.0, 6.7{\textpm}0.3, and 6.7{\textpm}0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5{\textpm}1.4, 11.1{\textpm}4.0, and 10.0{\textpm}2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P\&nbsp;= 0.001) and day 5 (P\&nbsp;= 0.015), and at several time points on day 8 (P \&lt; 0.05). CONCLUSIONS: Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.06.038},
	author = {Ciolino, Joseph B and Ross, Amy E and Tulsan, Rehka and Watts, Amy C and Wang, Rong-Fang and Zurakowski, David and Serle, Janet B and Kohane, Daniel S}
}
@article {1351149,
	title = {In vivo performance of a drug-eluting contact lens to treat glaucoma for a month},
	journal = {Biomaterials},
	volume = {35},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {432-9},
	abstract = {For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery, but achieving controlled drug release has been a significant challenge. We have developed a drug-eluting contact lens designed for prolonged delivery of latanoprost for the treatment of glaucoma, the leading cause of irreversible blindness worldwide. Latanoprost-eluting contact lenses were created by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon by ultraviolet light polymerization. In vitro and in vivo studies showed an early burst of drug release followed by sustained release for one month. Contact lenses containing thicker drug-polymer films demonstrated released a greater amount of drug after the initial burst. In vivo, single contact lenses were able to achieve, for at least one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with topical latanoprost solution, the current first-line treatment for glaucoma. The lenses appeared safe in cell culture and animal studies. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications.},
	keywords = {Animals, Contact Lenses, Drug Delivery Systems, Drug Stability, Glaucoma, Intraocular Pressure, Prostaglandins F, Synthetic, Rabbits},
	issn = {1878-5905},
	doi = {10.1016/j.biomaterials.2013.09.032},
	author = {Ciolino, Joseph B and Stefanescu, Cristina F and Ross, Amy E and Salvador-Culla, Borja and Cortez, Priscila and Ford, Eden M and Wymbs, Kate A and Sprague, Sarah L and Mascoop, Daniel R and Rudina, Shireen S and Sunia A Trauger and Cade, Fabiano and Kohane, Daniel S}
}
@article {439656,
	title = {Effect of alcaftadine 0.25\% on ocular itch associated with seasonal or perennial allergic conjunctivitis: a pooled analysis of two multicenter randomized clinical trials.},
	journal = {Clin Ophthalmol},
	volume = {9},
	year = {2015},
	month = {2015},
	pages = {765-72},
	abstract = {PURPOSE: Seasonal and perennial allergic conjunctivitis represent the majority of cases of ocular allergy. This analysis was designed to evaluate the efficacy and safety of once-daily alcaftadine 0.25\% in preventing ocular itching associated with seasonal or perennial allergic conjunctivitis. SUBJECTS AND METHODS: Pooled data from two double-masked, multicenter, placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis were analyzed. Subjects randomized to receive treatment with alcaftadine 0.25\% or placebo were challenged with seasonal (grass, ragweed, trees) or perennial (cat dander, cat hair, dog dander, dust mites, cockroach) allergens, 16 hours after treatment instillation. The primary efficacy measure was subject-evaluated mean ocular itching at 3 minutes post-CAC. Secondary measures included ocular itching at 5 and 7 minutes post-CAC. The proportion of subjects with minimal itch (itch score \&lt;1) and zero itch (itch score =0), and safety were also assessed. RESULTS: A total of 189 subjects enrolled in the two studies were treated with alcaftadine or placebo. Overall, 129 subjects were challenged with seasonal allergens and 60 subjects were challenged with perennial allergens. Alcaftadine 0.25\% achieved a statistically significant reduction in mean itch score at 3, 5, and 7 minutes post-CAC compared with placebo in subjects challenged with seasonal allergens (P\&lt;0.0001 at all time points) and those challenged with perennial allergens (P\&lt;0.0001 at all time points). A higher percentage of subjects treated with alcaftadine compared with placebo achieved minimal itch (P<=0.001 versus placebo at all time points) and zero itch (P\&lt;0.05 at all time points except 7 minutes for perennial) when challenged with either seasonal or perennial allergens. No treatment-related or serious adverse events were reported. CONCLUSION: Once-daily alcaftadine 0.25\% ophthalmic solution was well tolerated and demonstrated effective relief of ocular itching in subjects challenged with allergens classic for triggering either seasonal or perennial allergic conjunctivitis.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S80503},
	author = {Ciolino, Joseph B and McLaurin, Eugene B and Marsico, Nicholas P and Ackerman, Stacey L and Williams, Julia M and Villanueva, Linda and Hollander, David A}
}
@article {1608584,
	title = {MacuFix{\textregistered} versus Amsler grid for metamorphopsia categorization for macular diseases},
	journal = {Int Ophthalmol},
	volume = {42},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {229-238},
	abstract = {PURPOSE: Macular diseases often lead to metamorphopsia, which is traditionally tested using the Amsler grid. This study evaluates a novel method for assessing metamorphopsia, based on the software AMD-A Metamorphopsia Detector, application MacuFix{\textregistered}. METHODS: In this observational study, the usability of a new smartphone-based testing method to assess metamorphopsia was evaluated in 45 patients experiencing metamorphopsia in at least one eye using the questionnaire "System Usability Score (SUS)." Additionally, the diagnostic adherence of self-monitoring with the Amsler grid was compared to self-monitoring with the novel software MacuFix{\textregistered}. RESULTS: The average score of the SUS questionnaire in this study was 76.7 {\textpm} 15.5, corresponding to the "good" score on the grading scale. The average interval between two home administered tests was significantly shorter (6\&nbsp;days) when the application was used as compared to using the Amsler grid (19\&nbsp;days). The odds ratio of the frequency of patients using the application to the patients using the home test was 4. CONCLUSION: MacuFix{\textregistered} application can help in effective home monitoring of macular function as high user satisfaction and increased testing frequency was observed in its use in patients with macular diseases.},
	issn = {1573-2630},
	doi = {10.1007/s10792-021-02017-3},
	author = {Claessens, Daniela and Ichhpujani, Parul and Singh, Rohan Bir}
}
@article {1806541,
	title = {Infectious eye disease in the 21st century-an overview},
	journal = {Eye (Lond)},
	year = {2024},
	month = {2024 Feb 14},
	abstract = {Infectious diseases affecting the eye often cause unilateral or asymmetric visual loss in children and people of working age. This group of conditions includes viral, bacterial, fungal and parasitic diseases, both common and rare presentations which, in aggregate, may account for a significant portion of the global visual burden. Diagnosis is frequently challenging even in specialist centres, and many disease presentations are highly regional. In an age of globalisation, an understanding of the various modes of transmission and the geographic distribution of infections can be instructive to clinicians. The impact of eye infections on global disability is currently not sufficiently captured in global prevalence studies on visual impairment and blindness, which focus on bilateral disease in the over-50s. Moreover, in many cases it is hard to differentiate between infectious and immune-mediated diseases. Since infectious eye diseases can be preventable and frequently affect younger people, we argue that in future prevalence studies they should be considered as a separate category, including estimates of disability-adjusted life years (DALY) as a measure of overall disease burden. Numbers of ocular infections are uniquely affected by outbreaks as well as endemic transmission, and their control frequently relies on collaborative partnerships that go well beyond the remit of ophthalmology, encompassing domains as various as vaccination, antibiotic development, individual healthcare, vector control, mass drug administration, food supplementation, environmental and food hygiene, epidemiological mapping, and many more. Moreover, the anticipated impacts of global warming, conflict, food poverty, urbanisation and environmental degradation are likely to magnify their importance. While remote telemedicine can be a useful aide in the diagnosis of these conditions in resource-poor areas, enhanced global reporting networks and artificial intelligence systems may ultimately be required for disease surveillance and monitoring.},
	issn = {1476-5454},
	doi = {10.1038/s41433-024-02966-w},
	author = {Clare, Gerry and Kempen, John H and Pav{\'e}sio, Carlos}
}
@article {705056,
	title = {Plasma Kallikrein Mediates Vascular Endothelial Growth Factor-Induced Retinal Dysfunction and Thickening.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {6},
	year = {2016},
	month = {2016 May 1},
	pages = {2390-9},
	abstract = {PURPOSE: Plasma kallikrein is a serine protease and circulating component of inflammation, which exerts clinically significant effects on vasogenic edema. This study examines the role of plasma kallikrein in VEGF-induced retinal edema. METHODS: Intravitreal injections of VEGF and saline vehicle were performed in plasma prekallikrein-deficient (KLKB1-/-) and wild-type (WT) mice, and in both rats and mice receiving a selective plasma kallikrein inhibitor, VA999272. Retinal vascular permeability (RVP) and retinal thickness were measured by Evans blue permeation and optical coherence tomography, respectively. The retinal kallikrein kinin system was examined by Western blotting and immunohistochemistry. Retinal neovascularization was investigated in KLKB1-/- and WT mice subjected to oxygen-induced retinopathy. RESULTS: Vascular endothelial growth factor-induced RVP and retinal thickening were reduced in KLKB1-/- mice by 68\% and 47\%, respectively, compared to VEGF responses in WT mice. Plasma kallikrein also contributes to TNFα-induced retinal thickening, which was reduced by 52\% in KLKB1-/- mice. Systemic administration of VA999272 reduced VEGF-induced retinal thickening by 57\% (P \&lt; 0.001) in mice and 53\% (P \&lt; 0.001) in rats, compared to vehicle-treated controls. Intravitreal injection of VEGF in WT mice increased plasma prekallikrein in the retina, which was diffusely distributed throughout the inner and outer retinal layers. Avascular and neovascular areas induced by oxygen-induced retinopathy were similar in WT and KLKB1-/- mice. CONCLUSIONS: Vascular endothelial growth factor increases extravasation of plasma kallikrein into the retina, and plasma kallikrein is required for the full effects of VEGF on RVP and retinal thickening in rodents. Systemic plasma kallikrein inhibition may provide a therapeutic opportunity to treat VEGF-induced retina edema.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18272},
	author = {Clermont, Allen and Murugesan, Nivetha and Zhou, Qunfang and Kita, Takeshi and Robson, Peter A and Rushbrooke, Louise J and Evans, D Michael and Aiello, Lloyd Paul and Feener, Edward P}
}
@article {836786,
	title = {Scleritis in patients with granulomatosis with polyangiitis (Wegener).},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {1062-5},
	abstract = {AIMS: To describe and compare clinical features, complications and outcomes in patients with granulomatosis with polyangiitis (GPA)-associated scleritis with those seen in idiopathic and other autoimmune-associated scleritis, and to further describe the features that may serve as an indicator of life-threatening systemic disease. METHODS: We retrospectively reviewed electronic health records of all patients with scleritis seen at two tertiary care centres. Of 500 patients, 14 had GPA-associated scleritis and were included in this analysis. Measures included were age, gender, laterality, visual acuity and underlying systemic or ocular diseases. Clinical features (location, pain, inflammation) and ocular complications of these patients (decrease of vision, concomitant anterior uveitis and ocular hypertension) were studied and correlated. RESULTS: Fourteen of 500 patients with scleritis were GPA associated. Most of the patients with GPA-associated scleritis presented with sudden onset, bilateral, diffuse anterior scleral inflammation, with moderate-or-severe pain. Vision loss was not significantly different, and pain was more severe in these patients than in those with idiopathic scleritis. When compared with patients with other underlying autoimmune diseases, there were no significant differences found in epidemiological or clinical signs. Necrotising scleritis and corneal involvement were more commonly observed in GPA than in idiopathic scleritis and other autoimmune diseases and are often the presenting feature of the disease. CONCLUSIONS: The presence of necrotising changes or corneal involvement in the setting of scleral inflammation is highly suggestive of an underlying systemic vasculitis, of which GPA is the most common. These features should alert the doctor/optometrist and prompt a thorough diagnostic approach and an aggressive treatment given that it could reveal a life-threatening disease.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-307460},
	author = {Cocho, Lidia and Gonzalez-Gonzalez, Luis Alonso and Molina-Prat, Nicolas and Doctor, Priyanka and Sainz-de-la-Maza, Maite and Foster, C Stephen}
}
@article {1435397,
	title = {Oral guaifenesin for treatment of filamentary keratitis: A pilot study},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Apr 01},
	abstract = {PURPOSE: Pilot study to evaluate the safety and efficacy of oral guaifenesin in reducing the signs and symptoms of filamentary keratitis. METHODS: Prospective, uncontrolled open-label pilot study. Twelve patients with non-Sj{\"o}gren dry eye disease (DED) and secondary filamentary keratitis received treatment with oral guaifenesin 600 mg twice a day (total dose of 1.2 g/day) for 4 weeks. Adverse events, change in the number of corneal filaments, corneal fluorescein staining (CFS; NEI grading system), and symptoms (Ocular Surface Disease Index) were assessed. RESULTS: Before starting oral guaifenesin, all patients were on topical medical therapy for their condition. At baseline, the mean number of filaments was 5.8 {\textpm} 2.9, CFS score 7.3 {\textpm} 3.2, and OSDI score 55.6 {\textpm} 25. After 4 weeks of treatment, the number of filaments was 2.1 {\textpm} 2.2 (p = 0.04 vs. baseline), CFS score 6.5 {\textpm} 3.1 (p = 0.5), and OSDI score 46.1 {\textpm} 30.9 (p = 0.2). One patient discontinued the medication due to gastrointestinal side effects. CONCLUSIONS: Oral guaifenesin was safe and generally well tolerated, and demonstrated modest efficacy in reducing the severity of filamentary keratitis. These results should be considered preliminary; however, placebo-controlled investigations would be justified to evaluate the therapeutic efficacy of oral guaifenesin as a mucolytic in treatment of filamentary keratitis.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.03.008},
	author = {Coco, Giulia and Amparo, Francisco and Patel, Sangita P and Foulsham, William and Carreno-Galeano, Jimena Tatiana and Stockslager, Steven G and Ciolino, Joseph B and Yin, Jia and Dana, Reza}
}
@article {1466916,
	title = {Keratoconus progression associated with hormone replacement therapy},
	journal = {Am J Ophthalmol Case Rep},
	volume = {15},
	year = {2019},
	month = {2019 Sep},
	pages = {100519},
	abstract = {Purpose: To report a postmenopausal patient with keratoconus who experienced significant progression after using hormone replacement therapy. Observations: A 51-year-old woman with previously stable keratoconus presented with acute disease progression following hormone replacement therapy in the context of prophylactic hysterectomy and bilateral ovariosalpingectomy. Over a 14-month period after starting hormone therapy, the steepest K increased from 63.7D to 71.5D in the right eye and from 65.8D to 78.1D in the left eye. Conclusions: Hormone replacement therapy may amplify progression of keratoconus.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2019.100519},
	author = {Coco, Giulia and Kheirkhah, Ahmad and Foulsham, William and Dana, Reza and Ciolino, Joseph B}
}
@article {1470984,
	title = {Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10},
	journal = {Am J Transplant},
	volume = {20},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {389-398},
	abstract = {The functional competence of corneal endothelial cells (CEnCs) is critical for survival of corneal allografts, but these cells are often targets of the immune response mediated by graft-attacking effector T cells. Although regulatory T cells (Tregs) have been studied for their role in regulating the host{\textquoteright}s alloimmune response towards the graft, the cytoprotective function of these cells on CEnCs has not been investigated. The aim of this study was to determine whether Tregs suppress effector T cell-mediated and inflammatory cytokine-induced CEnC death, and to elucidate the mechanism by which this cytoprotection occurs. Using 2 well-established models of corneal transplantation (low-risk and high-risk models), we show that Tregs derived from low-risk graft recipients have a superior capacity in protecting CEnCs against effector T cell-mediated and interferon-γ and tumor necrosis factor-α-induced cell death compared to Tregs derived from high-risk hosts. We further demonstrate that the cytoprotective function of Tregs derived from low-risk hosts occurs independently of direct cell-cell contact and is mediated by the immunoregulatory cytokine IL-10. Our study is the first to report that Tregs provide cytoprotection for CEnCs through secretion of IL-10, indicating potentially novel therapeutic targets for enhancing CEnC survival following corneal transplantation.},
	issn = {1600-6143},
	doi = {10.1111/ajt.15631},
	author = {Coco, Giulia and Foulsham, William and Nakao, Takeshi and Yin, Jia and Amouzegar, Afsaneh and Taketani, Yukako and Chauhan, Sunil K and Dana, Reza}
}
@article {1517184,
	title = {Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy},
	journal = {Am J Hum Genet},
	volume = {106},
	number = {6},
	year = {2020},
	month = {2020 Jun 04},
	pages = {893-904},
	abstract = {Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous KIF3B variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G\&gt;C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by KIF3B. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T\&gt;C (p.Leu523Pro) KIF3B variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length in\&nbsp;vitro in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of KIF3B mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive KIF3B models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G\&gt;A (p.Ala334Thr) KIF3B variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and in\&nbsp;vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2020.04.005},
	author = {Cogn{\'e}, Benjamin and Latypova, Xenia and Senaratne, Lokuliyanage Dona Samudita and Martin, Ludovic and Koboldt, Daniel C and Georgios Kellaris and Fievet, Lorraine and Le Meur, Guyl{\`e}ne and Caldari, Dominique and Debray, Dominique and Nizon, Mathilde and Frengen, Eirik and Bowne, Sara J and 99 Lives Consortium and Cadena, Elizabeth L and Daiger, Stephen P and Bujakowska, Kinga M and Pierce, Eric A and Gorin, Michael and Katsanis, Nicholas and B{\'e}zieau, St{\'e}phane and Petersen-Jones, Simon M and Occelli, Laurence M and Lyons, Leslie A and Legeai-Mallet, Laurence and Sullivan, Lori S and Davis, Erica E and Isidor, Bertrand}
}
@article {1586167,
	title = {Serum Biomarkers in Neuro-Ophthalmology: When to Test},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {322-328},
	abstract = {Discovery and characterization of serologic biomarkers has revolutionized the diagnostic framework of systemic and paraneoplastic autoimmune neuro-ophthalmic diseases. Expanding recognition of the multiple ocular and visual manifestations of these conditions highlights the important role of the referring provider in identifying potential cases. Increasing ease of access to serologic testing also enables these practitioners to initiate the diagnostic work-up in suspected cases. We aimed to provide an update on the current knowledge surrounding and use of relevant autoimmune biomarkers by correlating specific clinical neuro-ophthalmic manifestations with autoantibody biomarkers. The utility of select biomarkers for myasthenia gravis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein-IgG-associated disorder, opsoclonus-myoclonus syndrome, anti-collapsin-response mediator protein-5 optic neuropathy, and glial fibrillary acidic protein-IgG-associated disease are discussed with particular focus on the clinical contexts in which to consider testing.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1897856},
	author = {Cohen, Devon A and Gise, Ryan and Gaier, Eric D}
}
@article {1318856,
	title = {Meningoencephalocele and Cerebrospinal Fluid Leak Complicating Orbital Decompression},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {3},
	year = {2018},
	month = {2018 May/Jun},
	pages = {e79-e81},
	abstract = {A 51-year-old man who had undergone right orbital decompression 5 months earlier developed a meningoencephalocele extending in the right sphenoid sinus through a skull base defect of the right ethmoid, sphenoid, and frontal bones. The authors report the third case to their knowledge of meningoencephalocele with cerebrospinal fluid leak after orbital decompression and discuss its management and measures that can be taken to prevent this rare but serious complication.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001055},
	author = {Cohen, Liza M and Jim{\'e}nez P{\'e}rez, Juan C and Holbrook, Eric H and Curry, William T and Yoon, Michael K}
}
@article {1474199,
	title = {Post-traumatic enophthalmos secondary to orbital fat atrophy: a volumetric analysis},
	journal = {Orbit},
	volume = {39},
	number = {5},
	year = {2020},
	month = {2020 Oct},
	pages = {319-324},
	abstract = {PURPOSE: To investigate via volumetric analysis whether orbital fat atrophy occurs in late post-traumatic enophthalmos. METHODS: An IRB-approved retrospective cohort study identified patients with diagnoses of both orbital fracture and enophthalmos with a CT orbits \&gt;3 months after injury. Exclusion criteria were surgical repair, other orbital disease or surgery, adjacent sinus disease, and an abnormal contralateral orbit. Images were analyzed using OsiriX imaging software (v.9.0.2, Pixmeo, Switzerland). Total orbital volume and orbital fat volume for the fractured and normal contralateral orbits were measured via three-dimensional volume rendering assisted region-of-interest computation. Enophthalmos was measured radiographically. Paired samples -tests were used to compare orbital fat and total orbital volumes between the fractured and normal contralateral orbits. RESULTS: Thirteen patients met the inclusion criteria. The numbers of patients with each fracture pattern were floor (4), medial wall (4), floor/medial wall (3), zygomaticomaxillary complex (floor+lateral wall) (1), zygomaticomaxillary complex+medial (inferior/medial/lateral walls) (1). Mean time from injury to CT scan was 21.8 {\textpm} 16.3 months. Comparing the fractured and normal contralateral orbits, there was a statistically significant decrease in orbital fat volume (mean difference 0.9 ml (14.2\%), = .0002) and increase in total orbital volume (mean difference 2.0 ml (7.0\%), = .0001). One ml orbital volume change was responsible for 0.83 mm enophthalmos. CONCLUSIONS: In addition to an increase in total orbital volume, orbital fat loss occurs with late post-traumatic enophthalmos due to unrepaired fractures. This suggests correction of bony change alone may be insufficient in some cases, and the use of custom implants may compensate for fat atrophy.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2019.1691607},
	author = {Cohen, Liza M and Habib, Larissa A and Yoon, Michael K}
}
@article {1655728,
	title = {Case 33-2022: An 11-Year-Old Girl with Redness of the Eyes},
	journal = {N Engl J Med},
	volume = {387},
	number = {17},
	year = {2022},
	month = {2022 Oct 27},
	pages = {1598-1607},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc2201235},
	author = {Cohen, Ezra M and Sobrin, Lucia and Figueiro Longo, Maria G and Pier, Danielle B and Brown, Daniel R and Stagner, Anna M}
}
@article {1179116,
	title = {Acquired Intermittent Pediatric Horner Syndrome due to Neuroblastoma},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {34},
	number = {2},
	year = {2018},
	month = {2018 Mar/Apr},
	pages = {e38-e41},
	abstract = {A 3-month-old male developed intermittent left upper eyelid ptosis at the age of 1 month that was gradually increasing in frequency and duration. Examination revealed anisocoria and left upper and lower eyelid ptosis, consistent with a left Horner syndrome. Imaging showed a mass in the left superior posterior mediastinum, which was resected, and pathology was consistent with neuroblastoma. Eight months thereafter, the patient underwent left upper eyelid ptosis repair. Cases of infantile acquired Horner syndrome due to neuroblastoma are rare. To the authors{\textquoteright} knowledge, there has only been one case described that presented with intermittent symptoms. The authors report the second case of intermittent acquired Horner syndrome due to neuroblastoma. This case demonstrates the importance of recognizing that Horner syndrome may present with subtle and intermittent symptoms. In a pediatric patient, one should maintain suspicion for neuroblastoma.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001001},
	author = {Cohen, Liza M and Elliott, Alexandra and Freitag, Suzanne K}
}
@article {1351150,
	title = {Clinical characteristics and current treatment of glaucoma},
	journal = {Cold Spring Harb Perspect Med},
	volume = {4},
	number = {6},
	year = {2014},
	month = {2014 Jun 02},
	abstract = {Glaucoma is a neurodegenerative disorder in which degenerating retinal ganglion cells (RGC) produce significant visual disability. Clinically, glaucoma refers to an array of conditions associated with variably elevated intraocular pressure (IOP) that contributes to RGC loss via mechanical stress, vascular abnormalities, and other mechanisms, such as immune phenomena. The clinical diagnosis of glaucoma requires assessment of the ocular anterior segment with slit lamp biomicroscopy, which allows the clinician to recognize signs of conditions that can produce elevated IOP. After measurement of IOP, a specialized prismatic lens called a gonioscope is used to determine whether the angle is physically open or closed. The structural manifestation of RGC loss is optic nerve head atrophy and excavation of the neuroretinal rim tissue. Treatment is guided by addressing secondary causes for elevated IOP (such as inflammation, infection, and ischemia) whenever possible. Subsequently, a variety of medical, laser, and surgical options are used to achieve a target IOP.},
	keywords = {Diagnostic Techniques, Ophthalmological, Glaucoma, Humans, Intraocular Pressure, Laser Therapy, Ophthalmologic Surgical Procedures, Retinal Ganglion Cells},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a017236},
	author = {Cohen, Laura P and Pasquale, Louis R}
}
@article {1351151,
	title = {A survey of preoperative blood tests in primary open-angle glaucoma patients versus cataract surgery patients},
	journal = {Digit J Ophthalmol},
	volume = {20},
	number = {2},
	year = {2014},
	month = {2014},
	pages = {20-8},
	abstract = {PURPOSE: To investigate biomarker differences in routine preoperative blood tests performed on primary open-angle glaucoma (POAG) case and control patients presenting for anterior segment eye surgery. METHODS: POAG cases and age-related cataract surgery patients (controls) who underwent anterior segment surgery at Massachusetts Eye and Ear from January 2009 through March 2012 were identified by retrospective record review. Patients with diabetes mellitus, secondary glaucoma, and cataract due to trauma or steroid exposure were excluded. Data on demographic features, preoperative ophthalmological and medical diagnosis, blood pressure, anthropometric measures, basic metabolic panel, and complete blood count were extracted from the medical records. Univariate differences in lab values between POAG cases and controls were assessed using unpaired t tests. Multivariate logistic regression analysis was completed to determine the independent associations of biomarkers with POAG. RESULTS: A total of 150 cases and 150 age-related controls were included. In multivariate analysis, higher AG was inversely associated with POAG (odds ratio [OR] = 0.90; 95\% confidence interval [CI], 0.80-1.00), and higher Cl- level was positively associated with POAG (OR = 1.15; 95\% CI, 1.02-1.29). The lower AG in POAG patients could be explained by higher IgG levels as the available data in post hoc analysis showed a nonsignificant trend toward higher IgG in cases compared to controls (17 vs 23; 1142 {\textpm} 284 mg/dl vs 1028 {\textpm} 291 mg/dl; P = 0.22). Furthermore, in multivariable analysis, a higher red blood cell count was also associated with POAG (OR = 1.91; 95\% CI, 1.11-3.28). CONCLUSIONS: Patients with POAG presenting for anterior segment surgery had a lower AG compared to age-related cataract surgery patients. The etiology of this reduced gap is unclear but the possible contribution of IgG warrants further exploration. The etiology of higher red blood cell counts in POAG cases is unknown and deserves further exploration.},
	keywords = {Acid-Base Equilibrium, Adult, Aged, Aged, 80 and over, Biomarkers, Case-Control Studies, Cataract, Cataract Extraction, Female, Glaucoma, Open-Angle, Humans, Immunoglobulin G, Male, Middle Aged, Potassium, Preoperative Period, Regression Analysis, Retrospective Studies},
	issn = {1542-8958},
	doi = {10.5693/djo.01.2014.02.002},
	author = {Cohen, Laura P and Wong, Jessica and Jiwani, Aliya Z and Greenstein, Scott H and Brauner, Stacey C and Chen, Sherleen C and Turalba, Angela V and Chen, Teresa C and Shen, Lucy and Rhee, Douglas J and Wiggs, Janey L and Kang, Jae Hee and Loomis, Stephanie and Pasquale, Louis R}
}
@article {1532354,
	title = {Radiographic analysis of fatty infiltration of the extraocular muscles in thyroid eye disease},
	journal = {Orbit},
	volume = {41},
	number = {1},
	year = {2022},
	month = {2022 Feb},
	pages = {53-58},
	abstract = {PURPOSE: Fatty infiltration of the extraocular muscles has been described radiographically in patients with thyroid eye disease (TED), yet it has not been studied on a large scale nor quantified. Our purpose was to define and characterize this entity in patients with TED. METHODS: An IRB-approved cross-sectional retrospective review of medical records identified patients with a clinical diagnosis of TED and at least one CT of the orbits. A 2:1 age and sex-matched control population consisted of patients without a history nor radiographic evidence of orbital disease or systemic thyroid abnormality. The presence of fatty infiltration in each extraocular rectus muscle was defined using Hounsfield units (HU). Laterality, muscles involved, and pattern of fatty infiltration were also evaluated. Student{\textquoteright}s t-tests, Chi-square, and Fisher{\textquoteright}s exact tests were used to compare TED and control groups. RESULTS: The study population consisted of 252 patients with TED and 504 age and sex-matched controls. Fatty infiltration was significantly more prevalent in TED patients (36/252, 14.3\%) compared to controls (11/504, 2.2\%) (p \&lt;\&nbsp;.001). The mean density of fat infiltration was significantly lower in TED patients (-40.4 HU) than controls (-34.8 HU) (p =\&nbsp;.048). In TED patients, the frequency of muscle involvement was inferior rectus (61.8\%), lateral rectus (19.7\%), superior rectus (11.8\%) and medial rectus (6.6\%), which was not significantly different than controls (p \&gt;\&nbsp;.05). Most muscles (88.2\%) in the TED group exhibited a heterogeneous pattern of infiltration, which did not differ from controls (p =\&nbsp;.34). CONCLUSIONS: This study characterizes fatty infiltration of the extraocular muscles in patients with TED.},
	keywords = {Cross-Sectional Studies, Graves Ophthalmopathy, Humans, Oculomotor Muscles, Orbit, Retrospective Studies},
	issn = {1744-5108},
	doi = {10.1080/01676830.2020.1817100},
	author = {Cohen, Liza M and Liou, Victor D and Cunnane, Mary Elizabeth and Yoon, Michael K}
}
@article {1445348,
	title = {Isolated Orbital Floor Fracture Management: A Survey and Comparison of American Oculofacial and Facial Plastic Surgeon Preferences},
	journal = {Craniomaxillofac Trauma Reconstr},
	volume = {12},
	number = {2},
	year = {2019},
	month = {2019 Jun},
	pages = {112-121},
	abstract = {This article aimed to characterize, compare, and contrast the management of isolated orbital floor fractures among oculofacial and facial plastic surgeons in the United States. An anonymous 17-question multiple-choice web-based survey was distributed to all 590 members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) and all 1,300 members of the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS) using each society{\textquoteright}s email database from November 2016 to January 2017. Two-hundred twenty-five oculofacial and 135 facial plastic surgeons completed the survey. The most important indications for surgery among both oculofacial and facial plastic surgeons were motility restriction, enophthalmos, and diplopia at 2 weeks. The most common preferred time to surgical intervention was 8 to 14 days; however, facial plastic surgeons were more likely to operate after 4 to 7 days (  \&lt; 0.001). The most common choices of orbital implant material were porous polyethylene and porous polyethylene plus titanium for both oculofacial and facial plastic surgeons, nylon for oculofacial surgeons, and titanium for facial plastic surgeons. The majority rarely/never used intraoperative computed tomography imaging or navigation. Facial plastic surgeons were more likely to perform postoperative imaging (  \&lt; 0.001). We report results of the first survey of isolated orbital floor fracture management among oculofacial and facial plastic surgeons in the United States. This survey characterizes practice patterns and areas of similarities/differences among oculofacial and facial plastic surgeons in the management of isolated orbital floor fractures, which may help define the current standard of care.},
	issn = {1943-3875},
	doi = {10.1055/s-0038-1639350},
	author = {Cohen, Liza M and Shaye, David A and Yoon, Michael K}
}
@article {630271,
	title = {Impact of treatment strategies for open angle glaucoma on intraocular pressure: the RiGOR study.},
	journal = {J Comp Eff Res},
	volume = {5},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {87-98},
	abstract = {AIMS: The RiGOR study{\textquoteright}s primary outcome measure was a 15\% reduction in intraocular pressure (IOP) for patients with open-angle glaucoma at 1 year. METHODS: Patients received treatment according to the ophthalmologist{\textquoteright}s usual practice. RESULTS: A higher proportion of patients in the incisional and other surgery group achieved a 15\% reduction in IOP than in the laser surgery or additional medication groups (82, 57, and 57\% respectively). In multivariate regression analyses, incisional surgery patients were 2.7-times as likely as patients treated with additional medication to achieve a 15\% reduction in IOP (odds ratio: 2.67; 95\% CI: 2.01-3.57). CONCLUSION: Incisional and other surgical procedures are effective treatments. There were no differences in treatment response by race or ethnicity.},
	issn = {2042-6313},
	doi = {10.2217/cer.15.58},
	author = {Coleman, Anne L and Lum, Flora C and Velentgas, Priscilla and Su, Zhaohui and Gliklich, Richard E and RiGOR Study Group}
}
@article {630276,
	title = {Practice patterns and treatment changes for open-angle glaucoma: the RiGOR study.},
	journal = {J Comp Eff Res},
	volume = {5},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {79-85},
	abstract = {AIMS: The RiGOR study provides a current picture of the types of glaucoma treatment over 12 months. METHODS: Patients were identified and enrolled at the time of decision to proceed with laser surgery procedure or other procedure such as incisional surgery or drainage device implantation, or initiation of a new or additional course of therapy with medication for glaucoma treatment. RESULTS: The most frequent type of treatments were prostaglandin analogues (60\%) among patients with additional medication, selective laser trabeculoplasty (87\%) among patients with laser surgery and trabeculectomy (57\%) among patients with incisional surgery. CONCLUSION: For 36\% of patients, a treatment cascade involves two or more therapies over a year. This demonstrates the complex nature of open-angle glaucoma treatment.},
	issn = {2042-6313},
	doi = {10.2217/cer.15.57},
	author = {Coleman, Anne L and Lum, Flora C and Velentgas, Priscilla and Su, Zhaohui and Gliklich, Richard E and RiGOR Study Group}
}
@article {630281,
	title = {RiGOR: a prospective observational study comparing the effectiveness of treatment strategies for open-angle glaucoma.},
	journal = {J Comp Eff Res},
	volume = {5},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {65-78},
	abstract = {AIMS: The RigOR study was designed to assess comparative effectiveness of medications, laser trabeculoplasty and incisional surgery in patients with open-angle glaucoma (OAG) in the community initiating a new or additional course of therapy as judged necessary by their ophthalmologist. This paper focuses specifically on demographic and clinical characteristics of OAG patients at enrollment. PATIENTS \&amp; METHODS: A total of 2597 with OAG already on medical therapy were enrolled from 45 community and academic practices throughout the USA. RESULTS: Overall, 784 (30\%) patients were treated with laser surgery, 436 with other surgical procedures (17\%), and 1377 with additional medication (53\%). Patients had mild (35\%) or moderate (31\%) glaucoma, with 28\% with severe glaucoma. CONCLUSION: The RiGOR study enrolled a diverse population and will provide valuable information regarding visual function and treatment patterns among different racial/ethnic populations. African-American and Hispanic patients entered the study with poorer visual acuity and more severe glaucoma.},
	issn = {2042-6313},
	doi = {10.2217/cer.15.56},
	author = {Coleman, Anne L and Lum, Flora C and Velentgas, Priscilla and Campion, Daniel and Su, Zhaohui and Gliklich, Richard E and RiGOR Study Group}
}
@article {630266,
	title = {Quality of life and visual acuity outcomes in the Registry in Glaucoma Outcomes Research study.},
	journal = {J Comp Eff Res},
	volume = {5},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {99-111},
	abstract = {AIMS: The RiGOR study evaluated the association of treatment and patient-reported outcomes for open-angle glaucoma patients. METHODS: The Glaucoma Symptom Scale (National Eye Institute-Visual Function Questionnaire (NEI-VFQ) and visual acuity (VA) were collected as quality of life measures. RESULTS: The proportion of patients with improvement of at least two lines of vision was highest in the incisional surgery group (14.2\% compared with 9.9\% for laser surgery and 10.9\% for additional medication). CONCLUSION: No clinically relevant differences were seen in benefit for the laser surgery or incisional surgery groups compared with additional medications for the Glaucoma Symptom Scale or NEI-VFQ measures or subscales. Differences in quality of life by race need to be explored in further studies.},
	issn = {2042-6313},
	doi = {10.2217/cer.15.59},
	author = {Coleman, Anne L and Lum, Flora C and Gliklich, Richard E and Velentgas, Priscilla and Su, Zhaohui and RiGOR Study Group}
}
@article {1626100,
	title = {EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma},
	journal = {Hum Mutat},
	volume = {43},
	number = {2},
	year = {2022},
	month = {2022 Feb},
	pages = {240-252},
	abstract = {Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A\&gt;T, p.Asn80Tyr; c.1480T\&gt;C, p.Ter494Glnext*29; and c.1429C\&gt;T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76\% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne{\textquoteright}s Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.},
	issn = {1098-1004},
	doi = {10.1002/humu.24320},
	author = {Collantes, Edward Ryan A and Delfin, Manuel S and Fan, Bao Jian and Torregosa, Justine May R and Siguan-Bell, Christine and Florcruz, Nilo Vincent de Guzman and Martinez, Jose Maria D and Masna-Hidalgo, Barbara Joy and Guzman, Vincent Paul T and Anotado-Flores, Jewel Faith and Levina, Faye D and Hernandez, Sophia Raine C and Collantes, Anthony A and Sibulo, Michael Carreon and Rong, Shi Song and Wiggs, Janey L}
}
@article {1517194,
	title = {Ocular injury via epinephrine auto-injector},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Jun 02},
	abstract = {Intraocular injury by epinephrine auto-injector has been rarely reported. Toxic risk to the intraocular structures is suspected, but the evidence is inconclusive. We present the case of a 2-year-old girl who sustained an injury to her right eye by inadvertent epinephrine injection. Cataract surgery was performed to treat an increasingly opaque lens, and an intraocular lens was implanted. The visual outcome was good, with no retinal damage.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.02.008},
	author = {Collett, Geoffrey and Elhusseiny, Abdelrahman M and Scelfo, Christina and Whitman, Mary C and VanderVeen, Deborah K}
}
@article {1586199,
	title = {Baseline vision results from the Baltimore Reading and Eye Disease Study},
	journal = {Can J Ophthalmol},
	volume = {57},
	number = {1},
	year = {2022},
	month = {2022 Feb},
	pages = {29-35},
	abstract = {OBJECTIVE: We describe the Baltimore Reading and Eye Disease Study, report baseline ocular findings, and explore the feasibility of eye examinations in the school setting. DESIGN: Prospective, school-based cohort study. PARTICIPANTS: Students in second and third grades. METHODS: Baseline eye examinations, including near and distance presenting visual acuity (VA), stereopsis, ocular alignment, dilated retinal examination, and cycloplegic refraction, were performed in 12 Baltimore public schools during the 2014-15 school year. MAIN OUTCOME MEASURES: Presenting VA, prevalence of refractive error, and other ocular findings. RESULTS: Among the 1054 eligible students, 321 participated. There were 271 (84.4\%) African American and 186 (57.9\%) female students; mean age was 7.9 {\textpm} 0.8 years. Cycloplegia was achieved in 308. The mean presenting distance and near VA was 0.1 {\textpm} 0.2 logMAR (range -0.1 to 1.5) and 0.1 {\textpm} 0.2 logMAR (range 0.0-1.6) in the better-seeing eye, respectively. The most common ocular findings were +1.00 diopter (D) or greater hyperopia (34.7\%), -0.50 D or greater myopia (29.5\%), 1.00 D or greater astigmatism (23.4\%), and convergence insufficiency (7.2\%). Thirty-seven (11.5\%) children needed referral to an eye care provider; 10\% of students required glasses full-time. CONCLUSIONS: Whereas the majority of second and third grade students in this study have good VA and minimal refractive error, 1 in 9 have an ocular finding necessitating further evaluation. It was feasible to conduct cycloplegic eye examinations in the school setting.},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2021.02.014},
	author = {Collins, Megan E and Guo, Xinxing and Mudie, Lucy I and Slavin, Robert E and Madden, Nancy and Chang, Dolly and Owoeye, Josephine and Repka, Michael X and Friedman, David S}
}
@article {1619414,
	title = {Quantification of retinal blood leakage in fundus fluorescein angiography in a retinal angiogenesis model},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Oct 06},
	pages = {19903},
	abstract = {Blood leakage from the vessels in the eye is the hallmark of many vascular eye diseases. One of the preclinical mouse models of retinal blood leakage, the very-low-density-lipoprotein receptor deficient mouse (Vldlr-/-), is used for drug screening and mechanistic studies. Vessel leakage is usually examined using Fundus fluorescein angiography (FFA). However, interpreting FFA images of the Vldlr-/- model is challenging as no automated and objective techniques exist for this model. A pipeline has been developed for quantifying leakage intensity and area including three tasks: (i) blood leakage identification, (ii) blood vessel segmentation, and (iii) image registration. Morphological operations followed by log-Gabor quadrature filters were used to identify leakage regions. In addition, a novel optic disk detection algorithm based on graph analysis was developed for registering the images at different timepoints. Blood leakage intensity and area measured by the methodology were compared to ground truth quantifications produced by two annotators. The relative difference between the quantifications from the method and those obtained from ground truth images was around 10\% {\textpm} 6\% for leakage intensity and 17\% {\textpm} 8\% for leakage region. The Pearson correlation coefficient between the method results and the ground truth was around 0.98 for leakage intensity and 0.94 for leakage region. Therefore, we presented a computational method for quantifying retinal vascular leakage and vessels using FFA in a preclinical angiogenesis model, the Vldlr-/- model.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-99434-2},
	author = {Comin, Cesar H and Tsirukis, Demetrios I and Sun, Ye and Xu, Xiaoyin}
}
@article {468976,
	title = {DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance.},
	journal = {Immunity},
	volume = {42},
	number = {6},
	year = {2015},
	month = {2015 Jun 16},
	pages = {1143-58},
	abstract = {Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T\&nbsp;cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in\&nbsp;vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.},
	issn = {1097-4180},
	doi = {10.1016/j.immuni.2015.05.009},
	author = {Conde, Patricia and Rodriguez, Mercedes and van der Touw, William and Jimenez, Ana and Burns, Matthew and Miller, Jennifer and Brahmachary, Manisha and Chen, Hui-Ming and Boros, Peter and Rausell-Palamos, Francisco and Yun, Tae Jin and Riquelme, Paloma and Rastrojo, Alberto and Aguado, Bego{\~n}a and Stein-Streilein, Joan and Tanaka, Masato and Zhou, Lan and Zhang, Junfeng and Lowary, Todd L and Ginhoux, Florent and Park, Chae Gyu and Cheong, Cheolho and Brody, Joshua and Turley, Shannon J and Lira, Sergio A and Bronte, Vincenzo and Gordon, Siamon and Heeger, Peter S and Merad, Miriam and Hutchinson, James and Chen, Shu-Hsia and Ochando, Jordi}
}
@article {603866,
	title = {Accuracy of a technology-assisted eye exam in evaluation of referable diabetic retinopathy and concomitant ocular diseases.},
	journal = {Br J Ophthalmol},
	volume = {99},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {1622-7},
	abstract = {BACKGROUND/AIMS: Digital retinal imaging using store-and-forward technology is used to screen for diabetic retinopathy (DR). Its usefulness in detecting non-diabetic eye diseases is uncertain. We determined the level of agreement between teleretinal imaging supplemented with visual acuity and intraocular pressure (IOP) measurements (ie, technology-assisted eye (TAE) exam) and a comprehensive eye exam in evaluation for DR and non-diabetic ocular conditions. METHODS: We conducted a prospective, observational study with two parallel evaluations. Patients with diabetes (n=317) had a TAE exam and a comprehensive eye exam on the same day. A subset of participants with normal baseline exams (n=72) had follow-up exams 1 year later. We measured the level of agreement for referable ocular findings. RESULTS: Agreement for referable ocular findings was moderate (n=389, agreement: 77\%; κ: 0.55), due in part to ungradable exams (22\%). However, about half of the ungradable exams had findings that warranted referral. There was substantial agreement for follow-up exams (n=72, agreement: 93\%; κ: 0.63). Among all gradable exams (n=303), the TAE exam had 86\% sensitivity and 84\% specificity for referable ocular findings, with high agreement (>=94\%) for DR and other major ocular diagnoses. CONCLUSIONS: There was moderate-to-substantial agreement between a TAE exam and a comprehensive eye exam for referable ocular findings in patients with diabetes. Ungradable exams were a frequent marker of ocular pathology. Teleretinal imaging may be a useful evaluation for both diabetic and non-diabetic ocular conditions.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-306536},
	author = {Conlin, Paul R and Asefzadeh, Baharak and Pasquale, Louis R and Selvin, Gerald and Lamkin, Rebecca and Cavallerano, Anthony A}
}
@article {313181,
	title = {Uncovering the connectivity of the brain in relation to novel vision rehabilitation strategies},
	journal = {Neurology},
	volume = {83},
	number = {6},
	year = {2014},
	month = {2014 Aug 05},
	pages = {484-5},
	keywords = {Brain, Electroencephalography, Humans, Nerve Net, Vision Disorders, Vision, Ocular, Visual Pathways},
	issn = {1526-632X},
	doi = {10.1212/WNL.0000000000000664},
	author = {Connell, Nyssa and Merabet, Lotfi B}
}
@article {1351153,
	title = {Action video game play and transfer of navigation and spatial cognition skills in adolescents who are blind},
	journal = {Front Hum Neurosci},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {133},
	abstract = {For individuals who are blind, navigating independently in an unfamiliar environment represents a considerable challenge. Inspired by the rising popularity of video games, we have developed a novel approach to train navigation and spatial cognition skills in adolescents who are blind. Audio-based Environment Simulator (AbES) is a software application that allows for the virtual exploration of an existing building set in an action video game metaphor. Using this ludic-based approach to learning, we investigated the ability and efficacy of adolescents with early onset blindness to acquire spatial information gained from the exploration of a target virtual indoor environment. Following game play, participants were assessed on their ability to transfer and mentally manipulate acquired spatial information on a set of navigation tasks carried out in the real environment. Success in transfer of navigation skill performance was markedly high suggesting that interacting with AbES leads to the generation of an accurate spatial mental representation. Furthermore, there was a positive correlation between success in game play and navigation task performance. The role of virtual environments and gaming in the development of mental spatial representations is also discussed. We conclude that this game based learning approach can facilitate the transfer of spatial knowledge and further, can be used by individuals who are blind for the purposes of navigation in real-world environments.},
	issn = {1662-5161},
	doi = {10.3389/fnhum.2014.00133},
	author = {Connors, Erin C and Chrastil, Elizabeth R and S{\'a}nchez, Jaime and Merabet, Lotfi B}
}
@article {1363257,
	title = {Development of an audio-based virtual gaming environment to assist with navigation skills in the blind},
	journal = {J Vis Exp},
	number = {73},
	year = {2013},
	month = {2013 Mar 27},
	abstract = {Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio based cues and set within the context of a video game metaphor, users gather relevant spatial information regarding a building{\textquoteright}s layout. This allows the user to develop an accurate spatial cognitive map of a large-scale three-dimensional space that can be manipulated for the purposes of a real indoor navigation task. After game play, participants are then assessed on their ability to navigate within the target physical building represented in the game. Preliminary results suggest that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building as indexed by their performance on a series of navigation tasks. These tasks included path finding through the virtual and physical building, as well as a series of drop off tasks. We find that the immersive and highly interactive nature of the AbES software appears to greatly engage the blind user to actively explore the virtual environment. Applications of this approach may extend to larger populations of visually impaired individuals.},
	keywords = {Adolescent, Adult, Audiovisual Aids, Blindness, Female, Humans, Male, Middle Aged, Play and Playthings, Software, User-Computer Interface, Young Adult},
	issn = {1940-087X},
	doi = {10.3791/50272},
	author = {Connors, Erin C and Yazzolino, Lindsay A and S{\'a}nchez, Jaime and Merabet, Lotfi B}
}
@article {1351152,
	title = {Virtual environments for the transfer of navigation skills in the blind: a comparison of directed instruction vs. video game based learning approaches},
	journal = {Front Hum Neurosci},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {223},
	abstract = {For profoundly blind individuals, navigating in an unfamiliar building can represent a significant challenge. We investigated the use of an audio-based, virtual environment called Audio-based Environment Simulator (AbES) that can be explored for the purposes of learning the layout of an unfamiliar, complex indoor environment. Furthermore, we compared two modes of interaction with AbES. In one group, blind participants implicitly learned the layout of a target environment while playing an exploratory, goal-directed video game. By comparison, a second group was explicitly taught the same layout following a standard route and instructions provided by a sighted facilitator. As a control, a third group interacted with AbES while playing an exploratory, goal-directed video game however, the explored environment did not correspond to the target layout. Following interaction with AbES, a series of route navigation tasks were carried out in the virtual and physical building represented in the training environment to assess the transfer of acquired spatial information. We found that participants from both modes of interaction were able to transfer the spatial knowledge gained as indexed by their successful route navigation performance. This transfer was not apparent in the control participants. Most notably, the game-based learning strategy was also associated with enhanced performance when participants were required to find alternate routes and short cuts within the target building suggesting that a ludic-based training approach may provide for a more flexible mental representation of the environment. Furthermore, outcome comparisons between early and late blind individuals suggested that greater prior visual experience did not have a significant effect on overall navigation performance following training. Finally, performance did not appear to be associated with other factors of interest such as age, gender, and verbal memory recall. We conclude that the highly interactive and immersive exploration of the virtual environment greatly engages a blind user to develop skills akin to positive near transfer of learning. Learning through a game play strategy appears to confer certain behavioral advantages with respect to how spatial information is acquired and ultimately manipulated for navigation.},
	issn = {1662-5161},
	doi = {10.3389/fnhum.2014.00223},
	author = {Connors, Erin C and Chrastil, Elizabeth R and S{\'a}nchez, Jaime and Merabet, Lotfi B}
}
@article {1474210,
	title = {Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry},
	journal = {JAMA},
	volume = {322},
	number = {17},
	year = {2019},
	month = {2019 11 05},
	pages = {1682-1691},
	abstract = {Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures: Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P \&lt; 5 {\texttimes} 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5\%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3\%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T\&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95\% CI, 1.20-1.46]; P = 2 {\texttimes} 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95\% CI, 1.09-1.21]; P \&lt; .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95\% CI, 1.14-1.25]; P = 4 {\texttimes} 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1\% in individuals of European or Asian ancestry. Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.},
	keywords = {Adaptor Proteins, Signal Transducing, African Continental Ancestry Group, Aged, Amyloid beta-Peptides, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glaucoma, Open-Angle, Humans, Immunohistochemistry, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors},
	issn = {1538-3598},
	doi = {10.1001/jama.2019.16161},
	author = {Genetics of Glaucoma in People of African Descent (GGLAD) Consortium and Hauser, Michael A and Allingham, R Rand and Aung, Tin and Van Der Heide, Carly J and Taylor, Kent D and Rotter, Jerome I and Wang, Shih-Hsiu J and Bonnemaijer, Pieter W M and Williams, Susan E and Abdullahi, Sadiq M and Abu-Amero, Khaled K and Anderson, Michael G and Akafo, Stephen and Alhassan, Mahmoud B and Asimadu, Ifeoma and Ayyagari, Radha and Bakayoko, Saydou and Nyamsi, Prisca Biangoup and Bowden, Donald W and Bromley, William C and Budenz, Donald L and Carmichael, Trevor R and Challa, Pratap and Chen, Yii-Der Ida and Chuka-Okosa, Chimdi M and Cooke Bailey, Jessica N and Costa, Vital Paulino and Cruz, Dianne A and DuBiner, Harvey and Ervin, John F and Feldman, Robert M and Flamme-Wiese, Miles and Gaasterland, Douglas E and Garnai, Sarah J and Girkin, Christopher A and Guirou, Nouhoum and Guo, Xiuqing and Haines, Jonathan L and Hammond, Christopher J and Herndon, Leon and Hoffmann, Thomas J and Hulette, Christine M and Hydara, Abba and Igo, Robert P and Jorgenson, Eric and Kabwe, Joyce and Kilangalanga, Ngoy Janvier and Kizor-Akaraiwe, Nkiru and Kuchtey, Rachel W and Lamari, Hasnaa and Li, Zheng and Liebmann, Jeffrey M and Liu, Yutao and Loos, Ruth J F and Melo, Monica B and Moroi, Sayoko E and Msosa, Joseph M and Mullins, Robert F and Nadkarni, Girish and Napo, Abdoulaye and Ng, Maggie C Y and Nunes, Hugo Freire and Obeng-Nyarkoh, Ebenezer and Okeke, Anthony and Okeke, Suhanya and Olaniyi, Olusegun and Olawoye, Olusola and Oliveira, Mariana Borges and Pasquale, Louise R and Perez-Grossmann, Rodolfo A and Pericak-Vance, Margaret A and Qin, Xue and Ramsay, Michele and Resnikoff, Serge and Richards, Julia E and Schimiti, Rui Barroso and Sim, Kar Seng and Sponsel, William E and Svidnicki, Paulo Vinicius and Thiadens, Alberta A H J and Uche, Nkechinyere J and van Duijn, Cornelia M and de Vasconcellos, Jos{\'e} Paulo Cabral and Wiggs, Janey L and Zangwill, Linda M and Risch, Neil and Milea, Dan and Ashaye, Adeyinka and Klaver, Caroline C W and Weinreb, Robert N and Ashley Koch, Allison E and Fingert, John H and Khor, Chiea Chuen}
}
@article {416931,
	title = {Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.},
	journal = {Mol Psychiatry},
	volume = {20},
	number = {5},
	year = {2015},
	month = {2015 May},
	pages = {647-56},
	abstract = {Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)\&gt;5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P\&lt;5 {\texttimes} 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.},
	issn = {1476-5578},
	doi = {10.1038/mp.2014.107},
	author = {Coffee and Caffeine Genetics Consortium and Cornelis, M C and Byrne, E M and Esko, T and Nalls, M A and Ganna, A and Paynter, N and Monda, K L and Amin, N and Fischer, K and Renstrom, F and Ngwa, J S and Huikari, V and Cavadino, A and Nolte, I M and Teumer, A and Yu, K and Marques-Vidal, P and Rawal, R and Manichaikul, A and Wojczynski, M K and Vink, J M and Zhao, J H and Burlutsky, G and Lahti, J and Mikkil{\"a}, V and Lemaitre, R N and Eriksson, J and Musani, S K and Tanaka, T and Geller, F and Luan, J and Hui, J and M{\"a}gi, R and Dimitriou, M and Garcia, M E and Ho, W-K and Wright, M J and Rose, L M and Magnusson, P K E and Pedersen, N L and Couper, D and Oostra, B A and Hofman, A and Ikram, M A and Tiemeier, H W and Uitterlinden, A G and van Rooij, F J A and Barroso, I and Johansson, I and Xue, L. and Kaakinen, M and Milani, L and Power, C and Snieder, H and Stolk, R P and Baumeister, S E and Biffar, R and Gu, F and Bastardot, F and Kutalik, Z and Jacobs, D R and Forouhi, N G and Mihailov, E and Lind, L and Lindgren, C and Micha{\"e}lsson, K and Morris, A and Jensen, M and Khaw, K-T and Luben, R N and Wang, J J and M{\"a}nnist{\"o}, S and Per{\"a}l{\"a}, M-M and K{\"a}h{\"o}nen, M and Lehtim{\"a}ki, T and Viikari, J and Mozaffarian, D. and Mukamal, K and Psaty, B M and D{\"o}ring, A and Heath, A.C. and Montgomery, G W and Dahmen, N and Carithers, T and Tucker, K L and Ferrucci, L and Boyd, H A and Melbye, M and Treur, J L and Mellstr{\"o}m, D and Hottenga, J J and Prokopenko, I and T{\"o}njes, A and Deloukas, P and Kanoni, S and Lorentzon, M and Houston, D K and Liu, Y. and Danesh, J and Rasheed, A and Mason, M A and Zonderman, A B and Franke, L and Kristal, B S and International Parkinson{\textquoteright}s Disease Genomics Consortium (IPDGC) and North American Brain Expression Consortium (NABEC) and UK Brain Expression Consortium (UKBEC) and Karjalainen, J and Reed, D R and Westra, H-J and Evans, M K and Saleheen, D and Harris, T B and Dedoussis, G and Curhan, G and Stumvoll, M and Beilby, J and Pasquale, L. R. and Feenstra, B and Bandinelli, S and Ordovas, J M and Chan, A T and Peters, U and Ohlsson, C and Gieger, C and Martin, N G and Waldenberger, M and Siscovick, D S and Raitakari, O and Eriksson, J G and Mitchell, P and Hunter, D J and Kraft, P and Rimm, E B and Boomsma, D I and Borecki, I B and Loos, R J F and Wareham, N J and Vollenweider, P and Caporaso, N and Grabe, H J and Neuhouser, M L and Wolffenbuttel, B H R and Hu, F B and Hypp{\"o}nen, E and J{\"a}rvelin, M-R and Cupples, L A and Franks, P W and Ridker, P M and van Duijn, C M and Heiss, G and Metspalu, A and North, K E and Ingelsson, E and Nettleton, J A and van Dam, R M and Chasman, D I}
}
@article {341716,
	title = {Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing.},
	journal = {Genet Med},
	volume = {17},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {253-61},
	abstract = {PURPOSE: Next-generation sequencing-based methods are being adopted broadly for genetic diagnostic testing, but the performance characteristics of these techniques with regard to test accuracy and reproducibility have not been fully defined. METHODS: We developed a targeted enrichment and next-generation sequencing approach for genetic diagnostic testing of patients with inherited eye disorders, including inherited retinal degenerations, optic atrophy, and glaucoma. In preparation for providing this genetic eye disease (GEDi) test on a CLIA-certified basis, we performed experiments to measure the sensitivity, specificity, and reproducibility, as well as the clinical sensitivity, of the test. RESULTS: The GEDi test is highly reproducible and accurate, with sensitivity and specificity of 97.9 and 100\%, respectively, for single-nucleotide variant detection. The sensitivity for variant detection was notably better than the 88.3\% achieved by whole-exome sequencing using the same metrics, because of better coverage of targeted genes in the GEDi test as compared with a commercially available exome capture set. Prospective testing of 192 patients with inherited retinal degenerations indicated that the clinical sensitivity of the GEDi test is high, with a diagnostic rate of 51\%. CONCLUSION: Based on quantified performance metrics, the data suggest that selective targeted enrichment is preferable to whole-exome sequencing for genetic diagnostic testing.Genet Med 17 4, 253-261.},
	issn = {1530-0366},
	doi = {10.1038/gim.2014.172},
	author = {Consugar, Mark B and Navarro-Gomez, Daniel and Place, Emily M and Bujakowska, Kinga M and Sousa, Maria E and Fonseca-Kelly, Zo{\"e} D and Taub, Daniel G and Janessian, Maria and Wang, Dan Yi and Au, Elizabeth D and Sims, Katherine B and Sweetser, David A and Fulton, Anne B and Liu, Qin and Wiggs, Janey L and Gai, Xiaowu and Pierce, Eric A}
}
@article {1363258,
	title = {Modulation of conjunctival goblet cell function by inflammatory cytokines},
	journal = {Mediators Inflamm},
	volume = {2013},
	year = {2013},
	month = {2013},
	pages = {636812},
	abstract = {Ocular surface inflammation associated with Sj{\"o}gren{\textquoteright}s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sj{\"o}gren{\textquoteright}s syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-α and IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.},
	keywords = {Animals, Apoptosis, Carbachol, Cell Proliferation, Cells, Cultured, Conjunctiva, Cytokines, Goblet Cells, Mice, Mice, Inbred C57BL, Mucin 5AC, Receptors, Cytokine, Th2 Cells, Thrombospondin 1},
	issn = {1466-1861},
	doi = {10.1155/2013/636812},
	author = {Contreras-Ruiz, L and Ghosh-Mitra, A and Shatos, M A and Dartt, D A and Masli, S}
}
@article {313236,
	title = {Polymorphism in THBS1 gene is associated with post-refractive surgery chronic ocular surface inflammation},
	journal = {Ophthalmology},
	volume = {121},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {1389-97},
	abstract = {PURPOSE: To determine the association of single nucleotide polymorphisms (SNPs) of the thrombospondin 1 (THBS1) gene with development of chronic ocular surface inflammation (keratoconjunctivitis) after refractive surgery. DESIGN: Retrospective cohort study. PARTICIPANTS: Active duty U.S. Army soldiers (n = 143) who opted for refractive surgery. METHODS: Conjunctival impression cytology samples collected from participants before the surgery were used to harvest DNA for genotyping 5 THBS1 SNPs (rs1478604, rs2228262, rs2292305, rs2228262, and rs3743125) using the Sequenom iPLEX Gold platform (Sequenom, San Diego, CA). Samples collected after surgery were used to harvest RNA for gene expression analysis by real-time polymerase chain reaction (PCR). Participants were followed for 1 year after surgery to monitor the status of keratoconjunctivitis. MAIN OUTCOME MEASURES: Genetic basis of the development of chronic keratoconjunctivitis after refractive surgery. RESULTS: Carriers of minor alleles of 3 SNPs each were found to be more susceptible to developing chronic keratoconjunctivitis (rs1478604: odds ratio [OR], 2.5; 95\% confidence interval [CI], 1.41-4.47; P = 2.5 {\texttimes} 10(-3); rs2228262 and rs2292305: OR, 1.9; 95\% CI, 1.05-3.51; P = 4.8 {\texttimes} 10(-2)). Carriers of the rs1478604 minor allele expressed significantly reduced levels of thrombospondin 1 (TSP1) (P = 0.042) and increased levels of an inflammatory cytokine associated with keratoconjunctivitis, interleukin-1β (P = 0.025), in their ocular surface epithelial cells compared with homozygous major allele controls. CONCLUSIONS: Genetic variation in the THBS1 gene that results in decreased expression of the encoded glycoprotein TSP1 in ocular surface epithelial cells significantly increases the susceptibility to develop chronic ocular surface inflammation after refractive surgery. Further investigation of THBS1 SNPs in a larger sample size is warranted.},
	keywords = {Adult, Chronic Disease, Cohort Studies, Dry Eye Syndromes, Female, Genotyping Techniques, Humans, Interleukin-1beta, Keratoconjunctivitis, Keratomileusis, Laser In Situ, Male, Military Personnel, Photorefractive Keratectomy, Polymorphism, Single Nucleotide, Postoperative Complications, Real-Time Polymerase Chain Reaction, Retrospective Studies, Thrombospondin 1, Transcriptome, United States, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.01.033},
	author = {Contreras-Ruiz, Laura and Ryan, Denise S and Sia, Rose K and Bower, Kraig S and Dartt, Darlene A. and Masli, Sharmila}
}
@article {560151,
	title = {Sj{\"o}gren{\textquoteright}s syndrome associated dry eye in a mouse model is ameliorated by topical application of integrin α4 antagonist GW559090.},
	journal = {Exp Eye Res},
	volume = {143},
	year = {2016},
	month = {2016 Feb},
	pages = {1-8},
	abstract = {Sj{\"o}gren{\textquoteright}s syndrome is an autoimmune disease associated with inflammation of exocrine glands with clinical manifestations of dry eye and dry mouth. Dry eye in this disease involves inflammation of the ocular surface tissues - cornea and conjunctiva. While systemic blockade of adhesion molecules has been used to treat autoimmune diseases, the purpose of this study was to determine the therapeutic efficacy of topical application of an integrin α4 adhesion molecule antagonist in a mouse model of dry eye associated with Sj{\"o}gren{\textquoteright}s syndrome. To assess this spontaneously developed ocular surface inflammation related to Sj{\"o}gren{\textquoteright}s syndrome in TSP-1null mice (12 wks) was evaluated. Mice were treated with topical formulations containing 0.1\% dexamethasone or 30\&nbsp;mg/ml GW559090 or vehicle control. Corneal fluorescein staining and conjunctival goblet cell density were assessed. Real-time PCR analysis was performed to assess expression of the inflammatory marker IL-1β in the cornea and Tbet and RORγt in the draining lymph nodes. Ocular surface inflammation was detectable in TSP-1null mice (>=12 wk old), which resulted in increased corneal fluorescein staining indicative of corneal barrier disruption and reduced conjunctival goblet cell density. These changes were accompanied by increased corneal expression of IL-1β as compared to WT controls and an altered balance of Th1 (Tbet) and Th17 (RORγt) markers in the draining lymph nodes. Topically applied dexamethasone and GW559090 significantly reduced corneal fluorescein staining compared to vehicle treatment (p\&nbsp;=\&nbsp;0.023 and p\&nbsp;\&lt;\&nbsp;0.001, respectively). This improved corneal barrier integrity upon adhesion molecule blockade was consistent with significantly reduced corneal expression of pro-inflammatory IL-1β compared to vehicle treated groups (p\&nbsp;\&lt;\&nbsp;0.05 for both treatments). Significant improvement in goblet cell density was also noted in mice treated with 0.1\% dexamethasone and GW559090 (p\&nbsp;\&lt;\&nbsp;0.05 for both). We conclude that similar to topical dexamethasone, topically administered GW559090 successfully improved corneal barrier integrity and inflammation in an established ocular surface disease associated with Sj{\"o}gren{\textquoteright}s syndrome.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2015.10.008},
	author = {Contreras-Ruiz, Laura and Mir, Fayaz A and Turpie, Bruce and Krauss, Achim H and Masli, Sharmila}
}
@article {1363259,
	title = {Conjunctival inflammation in thrombospondin-1 deficient mouse model of Sj{\"o}gren{\textquoteright}s syndrome},
	journal = {PLoS One},
	volume = {8},
	number = {9},
	year = {2013},
	month = {2013},
	pages = {e75937},
	abstract = {Lacrimal gland inflammation during autoimmune Sj{\"o}gren{\textquoteright}s syndrome (SS) leads to ocular surface inflammation - Keratoconjunctivitis sicca (KCS). This condition afflicts both the cornea and conjunctiva that form the ocular surface. Thrombospondin-1 (TSP-1) deficiency in mice results in lacrimal gland and corneal inflammation that resembles the human disease. In this study we report conjunctival pathology in this mouse model of SS. We found that TSP-1 null mice develop inflammation in the conjunctiva and associated loss of goblet cell function similar to that seen in patients with SS. Increased expression of Th1 (IFN-γ, TNF-α) and Th17 (IL-6, IL-17A) inflammatory cytokines and related transcription factors (Tbet and RORγt) were detected in TSP-1 null conjunctiva as well as their draining lymph nodes (LNs). The conjunctival inflammation was also accompanied by an increase in local lymphatic vessels. Interestingly, migration of antigen-bearing dendritic cells (DCs) from the ocular surface to the LNs was dependent on the TSP-1 available in the tissue. These results not only reveal potential immunopathogenic mechanisms underlying KCS in SS but also highlight the therapeutic potential of TSP-1.},
	keywords = {Animals, Cell Movement, Conjunctiva, Cytokines, Dendritic Cells, Disease Models, Animal, DNA Primers, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunohistochemistry, Lymph Nodes, Mice, Mice, Inbred C57BL, Real-Time Polymerase Chain Reaction, Sjogren{\textquoteright}s Syndrome, Thrombospondin 1},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0075937},
	author = {Contreras-Ruiz, Laura and Regenfuss, Birgit and Mir, Fayaz Ahmad and Kearns, James and Masli, Sharmila}
}
@article {1195246,
	title = {Dynamic Sensitivity of Corneal TRPM8 Receptors to Menthol Instillation in Dry Eye Versus Normal Subjects},
	journal = {J Ocul Pharmacol Ther},
	volume = {33},
	number = {9},
	year = {2017},
	month = {2017 Nov},
	pages = {686-692},
	abstract = {PURPOSE: To assess the sensitivity of corneal cold receptors to a known transient receptor potential melastatin 8 (TRPM8) agonist, menthol, in dry eye and normals, and to determine whether factors such as disease duration or age affect responses. METHODS: Dry eye disease (DED) (N = 33) and normal (N = 15) subjects were randomly assigned to receive Rohto{\textregistered} Hydra (0.01\% menthol) or Systane{\textregistered} Ultra treatments (OU) in a prospective, double-blind, crossover study. DED subjects had documented disease and symptom response scores \&gt;2 on a 0- to 5-point scale. Normals had no history of DED and scores \&lt;2 on the same scale. Endpoints included mean cooling score (0 = not cool and 10 = very cool) evaluated at 0, 0.5, 1, 2, 3, and 4 min post-instillation, sum cooling scores (5 time points, range 0-60), and ocular signs and symptoms. RESULTS: Mean ({\textpm}SD) ages were similar, 62.2 {\textpm} 8.6-year (DED) versus 53.5 {\textpm} 7.6-year (normal). Corneal sensitivity scores were not different between groups. Mean cooling scores at 0.5-4 min post-menthol instillation were significantly higher in DED subjects (P <= 0.03). Sum cooling scores were significantly higher (P = 0.04) in DED subjects with a disease duration \&lt;10 years (N = 18, 28.3 {\textpm} 2.58) versus >=10 years (N = 15, 20.2 {\textpm} 2.76). Age did not affect cooling response in either group. CONCLUSION: DED subjects had greater sensitivity to cold than normal subjects. DED duration, and not age, was critical to cooling sensitivity. The finding that cooling scores were higher in subjects with DED for less than 10 years compared to more than 10 years suggests that corneal cold receptor sensitivity decreases as the duration of DED increases.},
	issn = {1557-7732},
	doi = {10.1089/jop.2017.0050},
	author = {Corcoran, Peter and Hollander, David A and Ousler, George W and Angjeli, Endri and Rimmer, David and Lane, Keith and Abelson, Mark B}
}
@article {504011,
	title = {Anti-tumor necrosis factor-α therapy in uveitis.},
	journal = {Surv Ophthalmol},
	volume = {60},
	number = {6},
	year = {2015},
	month = {2015 Nov-Dec},
	pages = {575-89},
	abstract = {Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2015.06.004},
	author = {Cordero-Coma, Miguel and Sobrin, Lucia}
}
@article {1504064,
	title = {PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	number = {18},
	year = {2020},
	month = {2020 May 05},
	pages = {9922-9931},
	abstract = {The outer segments (OS) of rod and cone photoreceptor cells are specialized sensory cilia that contain hundreds of opsin-loaded stacked membrane disks that enable phototransduction. The biogenesis of these disks is initiated at the OS base, but the driving force has been debated. Here, we studied the function of the protein encoded by the photoreceptor-specific gene , which is mutated in inherited retinal dystrophy (RP54). We demonstrate that C2orf71/PCARE (photoreceptor cilium actin regulator) can interact with the Arp2/3 complex activator WASF3, and efficiently recruits it to the primary cilium. Ectopic coexpression of PCARE and WASF3 in ciliated cells results in the remarkable expansion of the ciliary tip. This process was disrupted by small interfering RNA (siRNA)-based down-regulation of an actin regulator, by pharmacological inhibition of actin polymerization, and by the expression of PCARE harboring a retinal dystrophy-associated missense mutation. Using human retinal organoids and mouse retina, we observed that a similar actin dynamics-driven process is operational at the base of the photoreceptor OS where the PCARE module and actin colocalize, but which is abrogated in mice. The observation that several proteins involved in retinal ciliopathies are translocated to these expansions renders it a potential common denominator in the pathomechanisms of these hereditary disorders. Together, our work suggests that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane at the initiation of new outer segment disk formation.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1903125117},
	author = {Corral-Serrano, Julio C and Lamers, Ideke J C and van Reeuwijk, Jeroen and Duijkers, Lonneke and Hoogendoorn, Anita D M and Yildirim, Adem and Argyrou, Nikoleta and Ruigrok, Renate A A and Letteboer, Stef J F and Butcher, Rossano and van Essen, Max D and Sakami, Sanae and van Beersum, Sylvia E C and Palczewski, Krzysztof and Cheetham, Michael E and Liu, Qin and Boldt, Karsten and Wolfrum, Uwe and Ueffing, Marius and Garanto, Alejandro and Roepman, Ronald and Collin, Rob W J}
}
@article {1664982,
	title = {The NLRP3 inflammasome - interleukin 1β axis in uveal melanoma},
	journal = {FEBS Open Bio},
	volume = {13},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {545-555},
	abstract = {Uveal melanoma (UM) is the most common primary intraocular cancer in the adult population. Recent studies suggested that the NLRP3 inflammasome could be a therapeutic target for cutaneous melanoma (CM), but the role of NLRP3 in UM remains unknown. Here, we analyzed the NLRP3-IL-1β axis in 5 UM and 4 CM cell lines. Expression of NLRP3 mRNA in UM and CM was low, and expression in UM was lower than in CM (P \&lt; 0.001). NLRP3 protein levels were below detection limit for all cell lines. UM exhibited lower baseline IL-1β secretion than CM, especially when compared to the Hs294t cell line (P \&lt; 0.05). Bioinformatic analysis of human tumor samples showed that UM has significantly lower expression of NLRP3 and IL-1β compared with CM. In conclusion, our work shows evidence of extremely low NLRP3 expression and IL-1β secretion by melanoma cells and highlight differences between CM and UM.},
	keywords = {Adult, Humans, Inflammasomes, Interleukin-1beta, Melanoma, NLR Family, Pyrin Domain-Containing 3 Protein, Skin Neoplasms},
	issn = {2211-5463},
	doi = {10.1002/2211-5463.13566},
	author = {Correa, Victor S M C and Efstathiou, Nikolaos E and Ntentakis, Dimitrios P and Yu, Zhen and Narimatsu, Toshio and Gragoudas, Evangelos and Kim, Ivana K and Vavvas, Demetrios G}
}
@article {1417553,
	title = {People With Central Vision Loss Have Difficulty Watching Videos},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {1},
	year = {2019},
	month = {2019 Jan 02},
	pages = {358-364},
	abstract = {Purpose: People with central vision loss (CVL) often report difficulties watching video. We objectively evaluated the ability to follow the story (using the information acquisition method). Methods: Subjects with CVL (n = 23) or normal vision (NV, n = 60) described the content of 30-second video clips from movies and documentaries. We derived an objective information acquisition (IA) score for each response using natural-language processing. To test whether the impact of CVL was simply due to reduced resolution, another group of NV subjects (n = 15) described video clips with defocus blur that reduced visual acuity to 20/50 to 20/800. Mixed models included random effects correcting for differences between subjects and between the clips, with age, gender, cognitive status, and education as covariates. Results: Compared to both NV groups, IA scores were worse for the CVL group (P \&lt; 0.001). IA reduced with worsening visual acuity (P \&lt; 0.001), and the reduction with worsening visual acuity was greater for the CVL group than the NV-defocus group (P = 0.01), which was seen as a greater discrepancy at worse levels of visual acuity. Conclusions: The IA method was able to detect difficulties in following the story experienced by people with CVL. Defocus blur failed to recreate the CVL experience. IA is likely to be useful for evaluations of the effects of vision rehabilitation.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-25540},
	author = {Costela, Francisco M and Saunders, Daniel R and Rose, Dylan J and Katjezovic, Sidika and Reeves, Stephanie M and Woods, Russell L}
}
@article {1282106,
	title = {The Preferred Retinal Locus Used to Watch Videos},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {14},
	year = {2017},
	month = {2017 Dec 01},
	pages = {6073-6081},
	abstract = {Purpose: Eccentric viewing is a common strategy used by people with central vision loss (CVL) to direct the eye such that the image falls onto functioning peripheral retina, known as the preferred retinal locus (PRL). It has been long acknowledged that we do not know whether the PRL used in a fixation test is also used when performing tasks. We present an innovative method to determine whether the same PRL observed during a fixation task was used to watch videos and whether poor resolution affects gaze location. Methods: The gaze of a group of 60 normal vision (NV) observers was used to define a democratic center of interest (COI) of video clips from movies and television. For each CVL participant (N = 20), we computed the gaze offsets from the COI across the video clips. The distribution of gaze offsets of the NV participants was used to define the limits of NV behavior. If the gaze offset was within this 95\% degree confidence interval, we presumed that the same PRL was used for fixation and video watching. Another 15 NV participants watched the video clips with various levels of defocus blur. Results: CVL participants had wider gaze-offset distributions than NV participants (P \&lt; 0.001). Gaze offsets of 18/20 CVL participants were outside the NV confidence interval. Further, none of the 15 NV participants watching the same videos with spherical defocus blur had a gaze offset that was decentered (outside the NV confidence interval), suggesting that resolution was not the problem. Conclusions: This indicates that many CVL participants were using a PRL to view videos that differed from that found with a fixation task and that it was not caused by poor resolution alone. The relationship between these locations needs further investigation.},
	keywords = {Adult, Aged, Aged, 80 and over, Eye Movements, Female, Fixation, Ocular, Healthy Volunteers, Humans, Male, Middle Aged, Motion Pictures, Retina, Scotoma, Visual Acuity, Visual Fields},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-21839},
	author = {Costela, Francisco M and Kajtezovic, Sidika and Woods, Russell L}
}
@article {1318857,
	title = {People with Hemianopia Report Difficulty with TV, Computer, Cinema Use, and Photography},
	journal = {Optom Vis Sci},
	volume = {95},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {428-434},
	abstract = {SIGNIFICANCE: Our survey found that participants with hemianopia report more difficulties watching video in various formats, including television (TV), on computers, and in a movie theater, compared with participants with normal vision (NV). These reported difficulties were not as marked as those reported by people with central vision loss. PURPOSE: The aim of this study was to survey the viewing experience (e.g., frequency, difficulty) of viewing video on TV, computers and portable visual display devices, and at the cinema of people with hemianopia and NV. This information may guide vision rehabilitation. METHODS: We administered a cross-sectional survey to investigate the viewing habits of people with hemianopia (n = 91) or NV (n = 192). The survey, consisting of 22 items, was administered either in person or in a telephone interview. Descriptive statistics are reported. RESULTS: There were five major differences between the hemianopia and NV groups. Many participants with hemianopia reported (1) at least "some" difficulty watching TV (39/82); (2) at least "some" difficulty watching video on a computer (16/62); (3) never attending the cinema (30/87); (4) at least some difficulty watching movies in the cinema (20/56), among those who did attend the cinema; and (5) never taking photographs (24/80). Some people with hemianopia reported methods that they used to help them watch video, including video playback and head turn. CONCLUSIONS: Although people with hemianopia report more difficulty with viewing video on TV and at the cinema, we are not aware of any rehabilitation methods specifically designed to assist people with hemianopia to watch video. The results of this survey may guide future vision rehabilitation.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001215},
	author = {Costela, Francisco M and Sheldon, Sarah S and Walker, Bethany and Woods, Russell L}
}
@article {1517198,
	title = {Validation of a vision-related activity scale for patients with retinitis pigmentosa},
	journal = {Health Qual Life Outcomes},
	volume = {18},
	number = {1},
	year = {2020},
	month = {2020 Jun 22},
	pages = {196},
	abstract = {PURPOSE: There have been few systematic reports of vision-related activity limitations of people with retinitis pigmentosa (RP). We report a merging of data from the National Eye Institute Visual Function Questionnaire (NEI-VFQ) obtained in five previous studies. We asked whether the Vision Function Scale (VFS; Pesudovs et al., 2010) which was developed for cataract patients would apply in this new population (condition). METHODS: Five hundred ninety-four individuals completed a total of 1753 questionnaires, with 209 participants providing responses over at least 4 years. Rasch analysis showed that the 15-item VFS was poorly targeted. A new instrument created by adding four driving-related items to the VFS had better targeting. As an indirect validation, VFS-plus person scores were compared to visual field area measured using a Goldmann perimeter, to the summed score for the combined 30-2 and 30/60-1 Humphrey Field Analyzer programs (HFA), to 30-Hz full-field cone electroretinogram (ERG) amplitude, and to ETDRS visual acuity. Changes in VFS-plus person scores with age and between four common heredity groups were also examined. RESULTS: The Rasch model of responses to the 19 VFS-plus items had person and item separation of 2.66 and 24.43 respectively. The VFS-plus person scores were related to each vision measure (p \&lt; 0.001). Over a five-year period, there was a reduction in person scores of 0.5 logits (p \&lt; 0.001). Person scores fell by an average of 0.34 logits per decade (p \&lt; 0.0001). Participants with an X-linked hereditary pattern had, on average, lower person scores (p \&lt; 0.001). CONCLUSIONS: The VFS-plus instrument quantified a highly-significant annual reduction in perceived vision-related ability over a five-year period. The outcome was consistent with clinical measures of vision, and detected lower perceived vision-related ability in participants with X-linked disease. It may be of use in future studies, but this needs to be tested in a representative population sample.},
	issn = {1477-7525},
	doi = {10.1186/s12955-020-01427-8},
	author = {Costela, Francisco M and Pesudovs, Konrad and Sandberg, Michael A and Weigel-DiFranco, Carol and Woods, Russell L}
}
@article {1417554,
	title = {When Watching Video, Many Saccades Are Curved and Deviate From a Velocity Profile Model},
	journal = {Front Neurosci},
	volume = {12},
	year = {2018},
	month = {2018},
	pages = {960},
	abstract = {Commonly, saccades are thought to be ballistic eye movements, not modified during flight, with a straight path and a well-described velocity profile. However, they do not always follow a straight path and studies of saccade curvature have been reported previously. In a prior study, we developed a real-time, saccade-trajectory prediction algorithm to improve the updating of gaze-contingent displays and found that saccades with a curved path or that deviated from the expected velocity profile were not well fit by our saccade-prediction algorithm (velocity-profile deviation), and thus had larger updating errors than saccades that had a straight path and had a velocity profile that was fit well by the model. Further, we noticed that the curved saccades and saccades with high velocity-profile deviations were more common than we had expected when participants performed a natural-viewing task. Since those saccades caused larger display updating errors, we sought a better understanding of them. Here we examine factors that could affect curvature and velocity profile of saccades using a pool of 218,744 saccades from 71 participants watching "Hollywood" video clips. Those factors included characteristics of the participants (e.g., age), of the videos (importance of faces for following the story, genre), of the saccade (e.g., magnitude, direction), time during the session (e.g., fatigue) and presence and timing of scene cuts. While viewing the video clips, saccades were most likely horizontal or vertical over oblique. Measured curvature and velocity-profile deviation had continuous, skewed frequency distributions. We used mixed-effects regression models that included cubic terms and found a complex relationship between curvature, velocity-profile deviation and saccade duration (or magnitude). Curvature and velocity-profile deviation were related to some video-dependent features such as lighting, face presence, or nature and human figure content. Time during the session was a predictor for velocity profile deviations. Further, we found a relationship for saccades that were in flight at the time of a scene cut to have higher velocity-profile deviations and lower curvature in univariable models. Saccades characteristics vary with a variety of factors, which suggests complex interactions between oculomotor control and scene content that could be explored further.},
	issn = {1662-4548},
	doi = {10.3389/fnins.2018.00960},
	author = {Costela, Francisco M and Woods, Russell L}
}
@article {1460361,
	title = {A free database of eye movements watching "Hollywood" videoclips},
	journal = {Data Brief},
	volume = {25},
	year = {2019},
	month = {2019 Aug},
	pages = {103991},
	abstract = {The provided database of tracked eye movements was collected using an infra-red, video-camera Eyelink 1000 system, from 95 participants as they viewed {\textquoteright}Hollywood{\textquoteright} video clips. There are 206 clips of 30-s and eleven clips of 30-min for a total viewing time of about 60 hours. The database also provides the raw 30-s video clip files, a short preview of the 30-min clips, and subjective ratings of the content of the videos for each in categories: (1) genre; (2) importance of human faces; (3) importance of human figures; (4) importance of man-made objects; (5) importance of nature; (6) auditory information; (7) lighting; and (8) environment type. Precise timing of the scene cuts within the clips and the democratic gaze scanpath position (center of interest) per frame are provided. At this time, this eye-movement dataset has the widest age range (22-85 years) and is the third largest (in recorded video viewing time) of those that have been made available to the research community. The data-acquisition procedures are described, along with participant demographics, summaries of some common eye-movement statistics, and highlights of research topics in which the database was used. The dataset is freely available in the Open Science Framework repository (link in the manuscript) and can be used without restriction for educational and research purposes, providing that this paper is cited in any published work.},
	issn = {2352-3409},
	doi = {10.1016/j.dib.2019.103991},
	author = {Costela, Francisco M and Woods, Russell L}
}
@article {1603870,
	title = {The Effect of Zoom Magnification and Large Display on Video Comprehension in Individuals With Central Vision Loss},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {8},
	year = {2021},
	month = {2021 07 01},
	pages = {30},
	abstract = {Purpose: A larger display at the same viewing distance provides relative-size magnification for individuals with central vision loss (CVL). However, the resulting large visible area of the display is expected to result in more head rotation, which may cause discomfort. We created a zoom magnification technique that placed the center of interest (COI) in the center of the display to reduce the need for head rotation. Methods: In a 2 {\texttimes} 2 within-subject study design, 23 participants with CVL viewed video clips from 1.5 m (4.9 feet) shown with or without zoom magnification, and with a large (208 cm/82" diagonal, 69{\textdegree}) or a typical (84 cm/33", 31{\textdegree}) screen. Head position was tracked and a custom questionnaire was used to measure discomfort. Results: Video comprehension was better with the large screen (P \&lt; 0.001) and slightly worse with zoom magnification (P = 0.03). Oddly, head movements did not vary with screen size (P = 0.63), yet were greater with zoom magnification (P = 0.001). This finding was unexpected, because the COI remains in the center with zoom magnification, but moves widely with a large screen and no magnification. Conclusions: This initial attempt to implement the zoom magnification method had flaws that may have decreased its effectiveness. In the future, we propose alternative implementations for zoom magnification, such as variable magnification. Translational Relevance: We present the first explicit demonstration that relative-size magnification improves the video comprehension of people with CVL when viewing video.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.8.30},
	author = {Costela, Francisco M and Reeves, Stephanie M and Woods, Russell L}
}
@article {1586166,
	title = {An implementation of Bubble Magnification did not improve the video comprehension of individuals with central vision loss},
	journal = {Ophthalmic Physiol Opt},
	volume = {41},
	number = {4},
	year = {2021},
	month = {2021 Jul},
	pages = {842-852},
	abstract = {PURPOSE: People with central vision loss (CVL) watch television, videos and movies, but often report difficulty and have reduced video comprehension. An approach to assist viewing videos is electronic magnification of the video itself, such as Bubble Magnification. METHODS: We created a Bubble Magnification technique that displayed a magnified segment around the centre of interest (COI) as determined by the gaze of participants with normal vision. The 15 participants with CVL viewed video clips shown with 2{\texttimes} and 3{\texttimes} Bubble Magnification, and unedited. We measured video comprehension and gaze coherence. RESULTS: Video comprehension was significantly worse with both 2{\texttimes} (p\&nbsp;=\&nbsp;0.01) and 3{\texttimes} Bubble Magnification (p\&nbsp;\&lt;\&nbsp;0.001) than the unedited video. There was no difference in gaze coherence across conditions (p\&nbsp;>=\&nbsp;0.58). This was unexpected because we expected a benefit in both video comprehension and gaze coherence. This initial attempt to implement the Bubble Magnification method had flaws that probably reduced its effectiveness. CONCLUSIONS: In the future, we propose alternative implementations of Bubble Magnification, such as variable magnification and bubble size. This study is a first step in the development of an intelligent-magnification approach to providing a vision rehabilitation aid to assist people with CVL.},
	issn = {1475-1313},
	doi = {10.1111/opo.12797},
	author = {Costela, Francisco M and Reeves, Stephanie M and Woods, Russell L}
}
@article {1328879,
	title = {Measuring the Difficulty Watching Video With Hemianopia and an Initial Test of a Rehabilitation Approach},
	journal = {Transl Vis Sci Technol},
	volume = {7},
	number = {4},
	year = {2018},
	month = {2018 Jul},
	pages = {13},
	abstract = {Purpose: If you cannot follow the story when watching a video, then the viewing experience is degraded. We measured the difficulty of following the story, defined as the ability to acquire visual information, which is experienced by people with homonymous hemianopia (HH). Further, we proposed and tested a novel rehabilitation aid. Methods: Participants watched 30-second directed video clips. Following each video clip, subjects described the visual content of the clip. An objective score of information acquisition (IA) was derived by comparing each new response to a control database of descriptions of the same clip using natural language processing. Study 1 compared 60 participants with normal vision (NV) to 24 participants with HH to test the hypothesis that participants with HH would score lower than NV participants, consistent with reports from people with HH that describe difficulties in video watching. In the second study, 21 participants with HH viewed clips with or without a superimposed dynamic cue that we called a content guide. We hypothesized that IA scores would increase using this content guide. Results: The HH group had a significantly lower IA score, with an average of 2.8, compared with 4.3 shared words of the NV group (mixed-effects regression, \&lt; 0.001). Presence of the content guide significantly increased the IA score by 0.5 shared words ( = 0.03). Conclusions: Participants with HH had more difficulty acquiring information from a video, which was objectively demonstrated (reduced IA score). The content guide improved information acquisition, but not to the level of people with NV. Translational Relevance: The value as a possible rehabilitation aid of the content guide warrants further study that involves an extended period of content-guide use and a randomized controlled trial.},
	issn = {2164-2591},
	doi = {10.1167/tvst.7.4.13},
	author = {Costela, Francisco M and Saunders, Daniel R and Kajtezovic, Sidika and Rose, Dylan J and Woods, Russell L}
}
@article {1347433,
	title = {Nailfold Capillary Morphology in Alzheimer{\textquoteright}s Disease Dementia},
	journal = {J Alzheimers Dis},
	year = {2018},
	month = {2018 Oct 06},
	abstract = {BACKGROUND: Cerebrovascular disease (CVD) is highly comorbid with Alzheimer{\textquoteright}s disease (AD), yet its role is not entirely understood. Nailfold video capillaroscopy (NVC) is a noninvasive method of live imaging the capillaries near the fingernail{\textquoteright}s cuticle and may help to describe further vascular contributions to AD. OBJECTIVE: To examine finger nailfold capillary morphology using NVC in subjects with AD dementia, mild cognitive impairment (MCI), and normal cognition (NC). METHODS: We evaluated nailfold capillary hemorrhages, avascular zones >=100 microns, and degree of tortuosity in 28 NC, 15 MCI, and 18 AD dementia subjects using NVC. Tortuosity was measured with a semi-quantitative rating scale. To assess the relation between nailfold capillary morphological features and diagnostic grouping, univariate and multivariable logistic regression models were fit to the data. RESULTS: 56\% of subjects with AD dementia compared to 14\% with NC and 13\% with MCI displayed moderate to severe tortuosity. Greater severity of tortuosity was associated with 10.6-fold (95\% confidence interval [CI]: 2.4, 46.2; p = 0.0018) and 7.4-fold (95\% CI: 1.3, 41.3; p = 0.023) increased odds of AD dementia relative to NC and MCI, respectively, after adjusting for multiple covariates. CONCLUSION: Greater nailfold capillary tortuosity was found in participants with AD dementia compared to those with MCI or NC. These data provide preliminary evidence of a systemic microvasculopathy in AD that may be noninvasively and inexpensively evaluated through NVC.},
	issn = {1875-8908},
	doi = {10.3233/JAD-180658},
	author = {Cousins, Clara C and Alosco, Michael L and Cousins, Henry C and Chua, Alicia and Steinberg, Eric G and Chapman, Kimberly R and Bing-Canar, Hanaan and Tripodis, Yorghos and Knepper, Paul A and Stern, Robert A and Pasquale, Louis R}
}
@article {987946,
	title = {Nailfold capillary morphology in exfoliation syndrome},
	journal = {Eye (Lond)},
	volume = {31},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {698-707},
	abstract = {PurposeThe purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy.Patients and methodsWe used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones >=200 microns (μm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95\% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models.ResultsAfter adjusting for multiple covariates, nailfold hemorrhages, avascular zones >=200 μm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend <=0.0001) and in POAG vs controls (P-for trend <=0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend=0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend=0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score >=1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95\% confidence interval: 1.5-13.3) relative to a tortuosity score \&lt;1.0 (P-for trend=0.005).ConclusionA high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.},
	issn = {1476-5454},
	doi = {10.1038/eye.2016.312},
	author = {Cousins, C C and Kang, J H and Bovee, C and Wang, J. and Greenstein, S H and Turalba, A and Shen, L Q and Brauner, S and Boumenna, T and Blum, S and Levkovitch-Verbin, H and Ritch, R and Wiggs, J L and Knepper, P A and Pasquale, L. R.}
}
@article {1504085,
	title = {Densitometric Profiles of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study},
	journal = {Am J Ophthalmol},
	volume = {217},
	year = {2020},
	month = {2020 09},
	pages = {10-19},
	abstract = {PURPOSE: The origin of blood in glaucoma-related disc hemorrhages (DH) remains unknown. A prior clinic-based study of primary open-angle glaucoma (POAG)-related DH showed that they had grayscale pixel intensities more similar to blood from retinal macroaneurysms and adjacent retinal arterioles than to blood from retinal vein occlusions or adjacent retinal venules, suggesting an arterial source. Here we assessed the densitometric profile of DH from fundus photographs in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Retrospective cross-sectional study of prospectively collected images. METHODS: Stereo disc photographs of 161 DH events from 83 OHTS participants (mean age [standard deviation (SD)]: 65.6 [9.2] years; 46.6\% female; 13.0\% black race) were imported into ImageJ to measure densitometry differences (adjacent arterioles minus DH [ΔA] or venules minus DH [ΔV]). Their size as percentage of disc area, ratio of length to midpoint width, and location relative to the disc margin were also analyzed. We performed t tests to compare ΔA and ΔV, analysis of variance to compare ΔA and ΔV across DH recurrent events, and multivariable linear regression to identify determinants of ΔA and ΔV. RESULTS: Mean (SD) ΔA and ΔV were\&nbsp;-2.2 (8.7) and\&nbsp;-11.4 (9.7) pixel intensity units, respectively (P \&lt; .001). ΔA and ΔV each did not differ significantly across recurrence of DH (P >= .92) or between DH events with and without POAG (P >= .26). CONCLUSIONS: OHTS DH had densitometric measurements more similar in magnitude to adjacent arterioles than venules, supporting an arterial origin for DH. Vascular dysregulation may contribute to disc hemorrhage formation in ocular hypertension.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.04.013},
	author = {Cousins, Clara C and Pan, Billy X and Chou, Jonathan C and Shen, Lucy Q and Gordon, Mae O and Kass, Michael A and Ritch, Robert and Pasquale, Louis R}
}
@article {1309949,
	title = {Resting nailfold capillary blood flow in primary open-angle glaucoma},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {203-207},
	abstract = {BACKGROUND/AIMS: An altered haemodynamic profile for various ocular posterior segment capillary beds has been documented in primary open-angle glaucoma (POAG). POAG may also involve abnormal non-ocular blood flow, and the nailfold capillaries, which are not affected by elevated intraocular pressure (IOP), are readily assessable. METHODS: We measured resting nailfold capillary blood flow in 67 POAG and 63 control subjects using video capillaroscopy. Masked readers tracked blood column voids between consecutive, registered image sequence frames, measured vessel diameter and calculated blood flow. We used multiple logistic regression to investigate the relation between nailfold capillary blood flow and POAG. In secondary analyses, we stratified cases by maximum IOP and concurrent topical beta-blocker use. RESULTS: Mean ({\textpm}SD) blood flow in picolitres\&nbsp;per\&nbsp;second was 26.8{\textpm}17.6 for POAG cases and 50.1{\textpm}24.2 for controls (p\&lt;0.0001). After adjustment for demographic and clinical factors including blood pressure and pulse, every picolitre\&nbsp;per\&nbsp;second increase in resting nailfold blood flow was associated with a 6\% (95\%\&nbsp;CI 0.92\&nbsp;to\&nbsp;0.96) reduced odds of POAG (p\&lt;0.0001). Similar relations between nailfold capillary blood flow and POAG were found for cases stratified by maximum known IOP and for cases stratified by concurrent topical beta-blocker use. CONCLUSION: Reduced resting nailfold capillary blood flow is present in POAG independent of covariates such as blood pressure, pulse and IOP.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-311846},
	author = {Cousins, Clara C and Chou, Jonathan C and Greenstein, Scott H and Brauner, Stacey C and Shen, Lucy Q and Turalba, Angela V and Houlihan, Patricia and Ritch, Robert and Wiggs, Janey L and Knepper, Paul A and Pasquale, Louis R}
}
@article {1806676,
	title = {Autoimmune Retinopathy: Intravenous Immunoglobulin Treatment vs. Natural History},
	journal = {Ophthalmol Retina},
	year = {2024},
	month = {2024 Feb 28},
	abstract = {This case-control study compared autoimmune retinopathy (AIR) outcomes in patients treated with intravenous immunoglobulin (IVIg) vs. those with no therapy. IVIg was associated with preservation of visual acuity and electroretinography parameters at longer term follow-up.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2024.02.011},
	author = {Cox, Jacob T and Minkus, Caroline L and Li, Ashley and Han, Samuel and Liu, Renee and Shah, Priya and Stanwyck, Lynn K and Rizzo, Joseph F and Sobrin, Lucia}
}
@article {1608585,
	title = {Alterations in corneal nerves in different subtypes of dry eye disease: An in vivo confocal microscopy study},
	journal = {Ocul Surf},
	volume = {22},
	year = {2021},
	month = {2021 Aug 15},
	pages = {135-142},
	abstract = {PURPOSE: To evaluate corneal subbasal nerve alterations in evaporative and aqueous-deficient dry eye disease (DED) as compared to controls. METHODS: In this retrospective, cross-sectional, controlled study, eyes with a tear break-up time of less than 10\&nbsp;s were classified as DED. Those with an anesthetized Schirmer{\textquoteright}s strip of less than 5\&nbsp;mm were classified as aqueous-deficient DED. Three representative in vivo confocal microscopy images were graded for each subject for total, main, and branch nerve density and numbers. RESULTS: Compared to 42 healthy subjects (42 eyes), the 70 patients with DED (139 eyes) showed lower total (18,579.0\&nbsp;{\textpm}\&nbsp;687.7\&nbsp;μm/mm2 vs. 21,014.7\&nbsp;{\textpm}\&nbsp;706.5, p\&nbsp;=\&nbsp;0.026) and main (7,718.9\&nbsp;{\textpm}\&nbsp;273.9 vs. 9,561.4\&nbsp;{\textpm}\&nbsp;369.8, p\&nbsp;\&lt;\&nbsp;0.001) nerve density, as well as lower total (15.5\&nbsp;{\textpm}\&nbsp;0.7/frame vs. 20.5\&nbsp;{\textpm}\&nbsp;1.3, p\&nbsp;=\&nbsp;0.001), main (3.0\&nbsp;{\textpm}\&nbsp;0.1 vs. 3.8\&nbsp;{\textpm}\&nbsp;0.2, p\&nbsp;=\&nbsp;0.001) and branch (12.5\&nbsp;{\textpm}\&nbsp;0.7 vs. 16.5\&nbsp;{\textpm}\&nbsp;1.2, p\&nbsp;=\&nbsp;0.004) nerve numbers. Compared to the evaporative DED group, the aqueous-deficient DED group showed reduced total nerve density (19,969.9\&nbsp;{\textpm}\&nbsp;830.7 vs. 15,942.2\&nbsp;{\textpm}\&nbsp;1,135.7, p\&nbsp;=\&nbsp;0.006), branch nerve density (11,964.9\&nbsp;{\textpm}\&nbsp;749.8 vs. 8,765.9\&nbsp;{\textpm}\&nbsp;798.5, p\&nbsp;=\&nbsp;0.006), total nerves number (16.9\&nbsp;{\textpm}\&nbsp;0.8/frame vs. 13.0\&nbsp;{\textpm}\&nbsp;1.2, p\&nbsp;=\&nbsp;0.002), and branch nerve number (13.8\&nbsp;{\textpm}\&nbsp;0.8 vs. 10.2\&nbsp;{\textpm}\&nbsp;1.1, p\&nbsp;=\&nbsp;0.002). CONCLUSIONS: Patients with DED demonstrate compromised corneal subbasal nerves, which is more pronounced in aqueous-deficient DED. This suggests a role for neurosensory abnormalities in the pathophysiology of DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.08.004},
	author = {Cox, Stephanie M and Kheirkhah, Ahmad and Aggarwal, Shruti and Abedi, Farshad and Cavalcanti, Bernardo M and Cruzat, Andrea and Hamrah, Pedram}
}
@article {1608590,
	title = {Targeting the NLRP3 Inflammasome in Glaucoma},
	journal = {Biomolecules},
	volume = {11},
	number = {8},
	year = {2021},
	month = {2021 Aug 19},
	abstract = {Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30-40\% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented.},
	issn = {2218-273X},
	doi = {10.3390/biom11081239},
	author = {Coyle, Sophie and Khan, Mohammed Naeem and Chemaly, Melody and Callaghan, Breedge and Doyle, Chelsey and Willoughby, Colin E and Atkinson, Sarah D and Gregory-Ksander, Meredith and McGilligan, Victoria}
}
@article {1483599,
	title = {Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression},
	journal = {Nat Genet},
	volume = {52},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {160-166},
	abstract = {Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10\% versus remaining 90\%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 {\texttimes} 10). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.},
	issn = {1546-1718},
	doi = {10.1038/s41588-019-0556-y},
	author = {Craig, Jamie E and Han, Xikun and Qassim, Ayub and Hassall, Mark and Cooke Bailey, Jessica N and Kinzy, Tyler G and Khawaja, Anthony P and An, Jiyuan and Marshall, Henry and Gharahkhani, Puya and Igo, Robert P and Graham, Stuart L and Healey, Paul R and Ong, Jue-Sheng and Zhou, Tiger and Siggs, Owen and Law, Matthew H and Souzeau, Emmanuelle and Ridge, Bronwyn and Hysi, Pirro G and Burdon, Kathryn P and Mills, Richard A and Landers, John and Ruddle, Jonathan B and Agar, Ashish and Galanopoulos, Anna and White, Andrew J R and Willoughby, Colin E and Andrew, Nicholas H and Best, Stephen and Vincent, Andrea L and Goldberg, Ivan and Radford-Smith, Graham and Martin, Nicholas G and Montgomery, Grant W and Vitart, Veronique and Hoehn, Rene and Wojciechowski, Robert and Jonas, Jost B and Aung, Tin and Pasquale, Louis R and Cree, Angela Jane and Sivaprasad, Sobha and Vallabh, Neeru A and NEIGHBORHOOD Consortium and UK Biobank Eye and Vision Consortium and Viswanathan, Ananth C and Pasutto, Francesca and Haines, Jonathan L and Klaver, Caroline C W and van Duijn, Cornelia M and Casson, Robert J and Foster, Paul J and Khaw, Peng Tee and Hammond, Christopher J and Mackey, David A and Mitchell, Paul and Lotery, Andrew J and Wiggs, Janey L and Hewitt, Alex W and Macgregor, Stuart}
}
@article {1137876,
	title = {TFOS DEWS II Report Executive Summary},
	journal = {Ocul Surf},
	volume = {15},
	number = {4},
	year = {2017},
	month = {2017 Oct},
	pages = {802-812},
	abstract = {This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.08.003},
	author = {Craig, Jennifer P and Nelson, J Daniel and Azar, Dimitri T and Belmonte, Carlos and Bron, Anthony J and Chauhan, Sunil K and de Paiva, Cintia S and Gomes, Jos{\'e} A P and Hammitt, Katherine M and Jones, Lyndon and Nichols, Jason J and Nichols, Kelly K and Novack, Gary D and Stapleton, Fiona J and Willcox, Mark D P and Wolffsohn, James S and Sullivan, David A}
}
@article {1309959,
	title = {Special Issue Introduction: Inherited Retinal Disease: Novel Candidate Genes, Genotype-Phenotype Correlations, and Inheritance Models},
	journal = {Genes (Basel)},
	volume = {9},
	number = {4},
	year = {2018},
	month = {2018 Apr 16},
	abstract = {Inherited retinal diseases (IRDs) are genetically and clinically heterogeneous disorders.[...].},
	issn = {2073-4425},
	doi = {10.3390/genes9040215},
	author = {Cremers, Frans P M and Boon, Camiel J F and Bujakowska, Kinga and Zeitz, Christina}
}
@article {1619418,
	title = {Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Oct 20},
	pages = {20729},
	abstract = {Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3\%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p \&lt; 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-00122-y},
	author = {Crespo-Trevi{\~n}o, Ricaurte Ramiro and Salinas-S{\'a}nchez, Anna Karen and Amparo, Francisco and Garza-Leon, Manuel}
}
@article {836791,
	title = {Patients{\textquoteright} Perspectives on Their Dry Eye Disease.},
	journal = {Ocul Surf},
	volume = {14},
	number = {4},
	year = {2016},
	month = {2016 Oct},
	pages = {440-446},
	abstract = {PURPOSE: Although it has been known that patients{\textquoteright} perspectives on their disease can significantly affect their level of functional disability as well as disease outcome, limited data are available on patients{\textquoteright} perceptions of their dry eye disease (DED). The aim of this questionnaire-based study was to evaluate patients{\textquoteright} perspectives on their DED. METHODS: This cross-sectional study included 91 patients with DED. In addition to clinical evaluation, all patients completed a questionnaire to evaluate their perspectives on their DED. This included their satisfaction with understanding DED, their opinion on the easiness of following doctors{\textquoteright} advice, their opinion on the effectiveness of the treatment, their satisfaction with the eye care, and their general outlook on DED. RESULTS: This study included 75 (82\%) women and 16 men (18\%) with a mean age of 57\&nbsp;{\textpm}\&nbsp;14\&nbsp;years who had been treated for DED for 5.2\&nbsp;{\textpm}\&nbsp;5.4\&nbsp;years. 93\% of the patients were satisfied with their understanding of DED, and 76\% found it easy to follow their doctors{\textquoteright} advice for DED management. Furthermore, 95\% thought that the DED treatment had been helpful and 95\% were satisfied with their eye care for DED. Forty-eight percent expressed optimism regarding the long-term prospects of their DED. CONCLUSIONS: Although the majority of DED patients have positive perspectives on their disease, close to half report a lack of optimism regarding the long-term outlook for their condition.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2016.06.001},
	author = {Crnej, Alja and Kheirkhah, Ahmad and Ren, Ai and Mullins, Andrew and Lavric, Alenka and Suri, Kunal and Hamrah, Pedram and Dana, Reza}
}
@article {692321,
	title = {Effect of Penetrating Keratoplasty and Keratoprosthesis Implantation on the Posterior Segment of the Eye.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {4},
	year = {2016},
	month = {2016 Apr 1},
	pages = {1643-8},
	abstract = {PURPOSE: To compare the effects of post-penetrating keratoplasty (PK) and post-keratoprosthesis (KPro) surgery-related inflammation on the posterior segment of the eye and to assess inhibition of tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) on these effects. METHODS: BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or miniature KPro (m-KPro) implantation. Intraocular pressure (IOP) was measured via an intracameral pressure sensor; tissues were harvested and analyzed 8 weeks after surgery. Expression of TNFα and IL-1β in the retina was analyzed using real-time quantitative (q)PCR. Optic nerve degeneration (axon count, circularity, and area) was assessed quantitatively using ImageJ software. After m-KPro implantation, mice were treated with saline, anti-TNFα, or anti-IL-1β antibody, and axonal loss was assessed after 10 weeks. RESULTS: Mean IOP was within normal limits in the operated and fellow eyes in all groups. The mRNA expression of TNFα and IL-1β was highest in m-KPro groups with either syngeneic or an allogeneic carrier. We observed optic nerve degeneration in both allogeneic PK and m-KPro implanted eyes with an allogeneic carrier. However, TNFα blockade significantly reduced axonal loss by 35\%. CONCLUSIONS: Allogeneic PK and m-KPro implants with an allogeneic carrier lead to chronic inflammation in the posterior segment of the eye, resulting in optic nerve degeneration. In addition, blockade of TNFα prevents axonal degeneration in this preclinical model of allogeneic m-KPro (alloKPro) implantation.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17557},
	author = {Crnej, Alja and Omoto, Masahiro and Dohlman, Thomas H and Gonzalez-Andrades, Miguel and Paschalis, Eleftherios I and Cruzat, Andrea and Vu, T H Khanh and Doorenbos, Marianne and Chen, Dong Feng and Dohlman, Claes H and Dana, Reza}
}
@article {345526,
	title = {Corneal inflammation after miniature keratoprosthesis implantation.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {1},
	year = {2015},
	month = {2015},
	pages = {185-9},
	abstract = {PURPOSE: To compare corneal inflammation after syngeneic and allogeneic penetrating keratoplasty (PK) with miniature Keratoprosthesis (m-KPro) implantation in mice. METHODS: BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or m-KPro implantation. Corneal inflammation was assessed by determining the frequencies of CD45(+) leukocytes, CD4(+) T cells, CD11b(+) cells, and Gr-1(+) granulocytes/monocytes by flow cytometry at 2, 4, and 8 weeks post transplantation. In addition, expression levels of the proinflammatory cytokines TNF-α and IL-1β were analyzed using real-time qPCR at 8 weeks post transplantation. RESULTS: Cell frequencies in the syngeneic (syn) and allogeneic (allo) m-KPro groups were higher compared with the syngeneic and allogeneic PK groups, respectively, at all time points. However, after week 4, frequencies of all analyzed immune cells were higher in the alloPK group as compared with synKPro group. At 8 weeks, the expression of TNF-α was higher in synKPro, alloPK, and alloKPro groups compared with the na{\"\i}ve and synPK groups. The expression of IL-1β was significantly higher in both KPro groups as compared with PK groups. CONCLUSIONS: Although the m-KPro device augments the inflammatory response in the cornea after its implantation, allogenicity (of the carrier tissue) is also a significant contributor to corneal inflammation. These data suggest that using syngeneic or decellularized corneal tissue as a Boston-KPro carrier could reduce the postoperative inflammation response.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15884},
	author = {Crnej, Alja and Omoto, Masahiro and Dohlman, Thomas H and Dohlman, Claes H and Dana, Reza}
}
@article {314121,
	title = {Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter.},
	journal = {EMBO Mol Med},
	volume = {6},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1175-90},
	abstract = {In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON-bipolar cells light-sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON-bipolar cells. This evokes high-frequency (~100\&nbsp;Hz) spiking responses in ganglion cells of previously blind, rd1, mice. Our vector is a promising vehicle for further development toward potential clinical use.},
	issn = {1757-4684},
	doi = {10.15252/emmm.201404077},
	author = {Cronin, Therese and Vandenberghe, Luk H and Hantz, P{\'e}ter and Juttner, Josephine and Reimann, Andreas and Kacs{\'o}, Agota-Enik{\H o} and Huckfeldt, Rachel M and Busskamp, Volker and Kohler, Hubertus and Lagali, Pamela S and Roska, Botond and Bennett, Jean}
}
@article {1460384,
	title = {Ocular motor manifestations of movement disorders},
	journal = {Curr Opin Ophthalmol},
	volume = {30},
	number = {6},
	year = {2019},
	month = {2019 Nov},
	pages = {443-448},
	abstract = {PURPOSE OF REVIEW: Impaired eye movements are frequently seen in ophthalmic and neurologic clinical practice, especially in individuals with movement disorders. Identification of the abnormal movement can aid initial diagnosis and improve understanding of the underlying disease pathophysiology. The present article reviews the ocular motor manifestations and recent research on them in common movement disorders. RECENT FINDINGS: Ocular motor manifestations and their pathophysiologic correlates are being defined. In particular, study of eye movements can help clarify the changing clinicopathologic spectrum of atypical parkinsonian disorders. The pathophysiology and natural history of blepharospasm are being elucidated. Recent research focuses on high-resolution imaging and other technological advances to improve the sensitivity of the ocular motility exam. Eye movements are being studied as biomarkers for diagnosis and progression in clinical care and trials. SUMMARY: The current review summarizes ocular motor manifestations in common movement disorders, and presents recent research investigating their cause and treatment.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000605},
	author = {Crotty, Grace F and Chwalisz, Bart K}
}
@article {1664983,
	title = {Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration},
	journal = {Hum Mol Genet},
	volume = {32},
	number = {2},
	year = {2023},
	month = {2023 Jan 06},
	pages = {204-217},
	abstract = {EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1 \&nbsp;R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3\&nbsp;months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17\&nbsp;months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P \&lt; 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65\% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.},
	keywords = {Animals, Complement Factor B, Female, Macular Degeneration, Male, Mice, Optic Disk Drusen, Retina, Retinal Pigment Epithelium},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddac187},
	author = {Crowley, Maura A and Garland, Donita L and Sellner, Holger and Banks, Angela and Fan, Lin and Rejtar, Tomas and Buchanan, Natasha and Delgado, Omar and Xu, Yong Yao and Jose, Sandra and Adams, Christopher M and Mogi, Muneto and Wang, Karen and Bigelow, Chad E and Poor, Stephen and Anderson, Karen and Jaffee, Bruce D and Prasanna, Ganesh and Grosskreutz, Cynthia and Fernandez-Godino, Rosario and Pierce, Eric A and Dryja, Thaddeus P and Liao, Sha-Mei}
}
@article {1351154,
	title = {Modifier genes as therapeutics: the nuclear hormone receptor Rev Erb alpha (Nr1d1) rescues Nr2e3 associated retinal disease},
	journal = {PLoS One},
	volume = {9},
	number = {1},
	year = {2014},
	month = {2014},
	pages = {e87942},
	abstract = {Nuclear hormone receptors play a major role in many important biological processes. Most nuclear hormone receptors are ubiquitously expressed and regulate processes such as metabolism, circadian function, and development. They function in these processes to maintain homeostasis through modulation of transcriptional gene networks. In this study we evaluate the effectiveness of a nuclear hormone receptor gene to modulate retinal degeneration and restore the integrity of the retina. Currently, there are no effective treatment options for retinal degenerative diseases leading to progressive and irreversible blindness. In this study we demonstrate that the nuclear hormone receptor gene Nr1d1 (Rev-Erbα) rescues Nr2e3-associated retinal degeneration in the rd7 mouse, which lacks a functional Nr2e3 gene. Mutations in human NR2E3 are associated with several retinal degenerations including enhanced S cone syndrome and retinitis pigmentosa. The rd7 mouse, lacking Nr2e3, exhibits an increase in S cones and slow, progressive retinal degeneration. A traditional genetic mapping approach previously identified candidate modifier loci. Here, we demonstrate that in vivo delivery of the candidate modifier gene, Nr1d1 rescues Nr2e3 associated retinal degeneration. We observed clinical, histological, functional, and molecular restoration of the rd7 retina. Furthermore, we demonstrate that the mechanism of rescue at the molecular and functional level is through the re-regulation of key genes within the Nr2e3-directed transcriptional network. Together, these findings reveal the potency of nuclear receptors as modulators of disease and specifically of NR1D1 as a novel therapeutic for retinal degenerations.},
	keywords = {Animals, Eye Diseases, Hereditary, Genetic Therapy, Humans, Mice, Mice, Transgenic, Nuclear Receptor Subfamily 1, Group D, Member 1, Orphan Nuclear Receptors, Retinal Degeneration, Retinitis Pigmentosa, Vision Disorders},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0087942},
	author = {Cruz, Nelly M and Yuan, Yang and Leehy, Barrett D and Baid, Rinku and Kompella, Uday and Deangelis, Margaret M and Escher, Pascal and Haider, Neena B}
}
@article {836796,
	title = {Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.},
	journal = {Ophthalmology},
	volume = {123},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {2248-54},
	abstract = {PURPOSE: The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. DESIGN: Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients{\textquoteright} native residual vision compared with their vision with the Argus II. PARTICIPANTS: Thirty participants in 10 centers in the United States and Europe. METHODS: The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. RESULTS: Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. CONCLUSIONS: The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.06.049},
	author = {da Cruz, Lyndon and Dorn, Jessy D and Humayun, Mark S and Dagnelie, Gislin and Handa, James and Barale, Pierre-Olivier and Sahel, Jos{\'e}-Alain and Stanga, Paulo E and Hafezi, Farhad and Safran, Avinoam B and Salzmann, Joel and Santos, Arturo and Birch, David and Spencer, Rand and Cideciyan, Artur V and de Juan, Eugene and Duncan, Jacque L and Eliott, Dean and Fawzi, Amani and Olmos de Koo, Lisa C and Ho, Allen C and Brown, Gary and Haller, Julia and Regillo, Carl and Del Priore, Lucian V and Arditi, Aries and Greenberg, Robert J and Argus II Study Group}
}
@article {1295859,
	title = {Colocalization of Galectin-3 With CD147 Is Associated With Increased Gelatinolytic Activity in Ulcerating Human Corneas},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {1},
	year = {2018},
	month = {2018 Jan 01},
	pages = {223-230},
	abstract = {Purpose: Galectin-3 is a carbohydrate-binding protein known to promote expression of matrix metalloproteinases, a hallmark of ulceration, through interaction with the extracellular matrix metalloproteinase inducer CD147. The aim of this study was to investigate the distribution of galectin-3 in corneas of patients with ulcerative keratitis and to determine its relationship to CD147 and the presence of gelatinolytic activity. Methods: This was an observational case series involving donor tissue from 13 patients with active corneal ulceration and 6 control corneas. Fixed-frozen sections of the corneas were processed to localize galectin-3 and CD147 by immunofluorescence microscopy. Gelatinolytic activity was detected by in situ zymography. Results: Tissue from patients with active corneal ulceration showed a greater galectin-3 immunoreactivity in basal epithelia and stroma compared with controls. Immunofluorescence grading scores revealed increased colocalization of galectin-3 and CD147 in corneal ulcers at the epithelial-stromal junction and within fibroblasts. Quantitative analysis using the Manders{\textquoteright} colocalization coefficient demonstrated significant overlap in corneas from patients with ulcerative keratitis (M1 = 0.29; M2 = 0.22) as opposed to control corneas (M1 = 0.01, P \&lt; 0.01; M2 = 0.02, P \&lt; 0.05). In these experiments, there was a significant positive correlation between the degree of galectin-3 and CD147 colocalization and the presence of gelatinolytic activity. Conclusions: Our results indicate that concomitant stimulation and colocalization of galectin-3 with CD147 are associated with increased gelatinolytic activity in the actively ulcerating human cornea and suggest a mechanism by which galectin-3 may contribute to the degradation of extracellular matrix proteins during ulceration.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-23196},
	author = {Cruzat, Andrea and Gonzalez-Andrades, Miguel and Mauris, J{\'e}r{\^o}me and AbuSamra, Dina B and Chidambaram, Preethi and Kenyon, Kenneth R and Chodosh, James and Dohlman, Claes H and Arg{\"u}eso, Pablo}
}
@article {1363260,
	title = {Wound anatomy after type 1 Boston KPro using oversized back plates},
	journal = {Cornea},
	volume = {32},
	number = {12},
	year = {2013},
	month = {2013 Dec},
	pages = {1531-6},
	abstract = {PURPOSE: To compare the anatomy of the graft-host junction and anterior chamber angle after Boston Keratoprosthesis (KPro) placement using oversized (9.5-mm) and standard (8.5-mm) back plates. METHODS: Six patients with 9.5-mm titanium back plates and 10 patients with 8.5-mm titanium back plates were imaged by anterior segment optical coherence tomography 6 to 12 months after KPro placement. The location of the graft-host junction in relation to the back plate, the corneal thickness at the graft-host junction, and the anterior chamber angle were assessed. The clinical outcomes and incidence of retroprosthetic membrane (RPM) formation in this cohort were retrospectively evaluated. RESULTS: The oversized back plates completely covered the graft-host junction in all quadrants, allowing the complete apposition of the posterior surface of the carrier graft with the host cornea, with decreased graft-host junction wound thickness. The standard back plates covered the posterior aspect of the carrier graft but not the graft-host junction or the host cornea, resulting in a significantly thicker graft-host junction. None of the patients with larger back plates developed a significant RPM during a 12-month follow-up period. One patient with a larger back plate developed a corneal melt at the KPro stem as a result of chronic exposure. CONCLUSIONS: Oversized KPro back plates effectively cover the graft-host junction without any adverse effects on angle anatomy or wound healing. This may be a strategy to provide better wound apposition, reduce RPM formation, and reduce angle closure from iris synechiae to the wound.},
	keywords = {Adult, Aged, Anterior Eye Segment, Artificial Organs, Cornea, Corneal Diseases, Female, Humans, Male, Middle Aged, Prosthesis Implantation, Retrospective Studies, Titanium, Tomography, Optical Coherence, Wound Healing},
	issn = {1536-4798},
	doi = {10.1097/ICO.0b013e3182a854ac},
	author = {Cruzat, Andrea and Shukla, Anita and Dohlman, Claes H and Colby, Kathryn}
}
@article {560211,
	title = {Contralateral Clinically Unaffected Eyes of Patients With Unilateral Infectious Keratitis Demonstrate a Sympathetic Immune Response.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {11},
	year = {2015},
	month = {2015 Oct 1},
	pages = {6612-20},
	abstract = {PURPOSE: To analyze the contralateral unaffected eyes of patients with microbial keratitis (MK) for any immune cell or nerve changes by laser in vivo confocal microscopy (IVCM). METHODS: A prospective study was performed on 28 patients with MK, including acute bacterial, fungal, and Acanthamoeba keratitis, as well as on their contralateral clinically unaffected eyes and on control groups, which consisted of 28 age-matched normal controls and 15 control contact lens (CL) wearers. Laser IVCM with the Heidelberg Retinal Tomograph 3/Rostock Cornea Module and Cochet-Bonnet esthesiometry of the central cornea were performed. Two masked observers assessed central corneal dendritiform cell density and subbasal corneal nerve parameters. RESULTS: The contralateral clinically unaffected eyes of patients with MK demonstrated significant diminishment in nerve density (15,603.8 {\textpm} 1265.2 vs. 24,102.1 {\textpm} 735.6 μm/mm2), total number of nerves (11.9 {\textpm} 1.0 vs. 24.9 {\textpm} 1.2/frame), number of branches (1.7 {\textpm} 0.2 vs. 19.9 {\textpm} 1.3/frame), and branch nerve length (5775.2 {\textpm} 757.1 vs. 12,715.4 {\textpm} 648.4 μm/mm2) (P \&lt; 0.001 for all parameters) compared to normal controls and CL wearers. Further, dendritiform cell density in the contralateral unaffected eyes was significantly increased as compared to that in controls (117.5 {\textpm} 19.9 vs. 24.2 {\textpm} 3.5 cells/mm2, P \&lt; 0.001). CONCLUSIONS: We demonstrate a subclinical involvement in the contralateral clinically unaffected eyes in patients with unilateral acute MK. In vivo confocal microscopy reveals not only a diminishment of the subbasal corneal nerves and sensation, but also an increase in dendritiform cell density in the contralateral unaffected eyes of MK patients. These findings show bilateral immune alterations in a clinically unilateral disease.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-16560},
	author = {Cruzat, Andrea and Schrems, Wolfgang A and Schrems-Hoesl, Laura M and Cavalcanti, Bernardo M and Baniasadi, Neda and Witkin, Deborah and Pavan-Langston, Deborah and Dana, Reza and Hamrah, Pedram}
}
@article {1363261,
	title = {Low-cost and readily available tissue carriers for the Boston keratoprosthesis: a review of possibilities},
	journal = {J Ophthalmol},
	volume = {2013},
	year = {2013},
	month = {2013},
	pages = {686587},
	abstract = {The Boston keratoprosthesis (B-KPro), currently the most commonly used artificial cornea worldwide, can provide rapid visual rehabilitation for eyes with severe corneal opacities not suitable for standard corneal transplantation. However, the B-KPro presently needs a corneal graft as a tissue carrier. Although corneal allograft tissue is readily available in the United States and other developed countries with established eye banks, the worldwide need vastly exceeds supply. Therefore, a simple, safe, and inexpensive alternative to corneal allografts is desirable for the developing world. We are currently exploring reasonable alternative options such as corneal autografts, xenografts, noncorneal autologous tissues, and laboratory-made tissue constructs, as well as modifications to corneal allografts, such as deep-freezing, glycerol-dehydration, gamma irradiation, and cross-linking. These alternative tissue carriers for the B-KPro are discussed with special regard to safety, practicality, and cost for the developing world.},
	issn = {2090-004X},
	doi = {10.1155/2013/686587},
	author = {Cruzat, Andrea and Tauber, Allyson and Shukla, Anita and Paschalis, Eleftherios I and Pineda, Roberto and Dohlman, Claes H}
}
@article {705061,
	title = {Corneal Reinnervation and Sensation Recovery in Patients With Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves.},
	journal = {Cornea},
	volume = {35},
	number = {5},
	year = {2016},
	month = {2016 May},
	pages = {619-25},
	abstract = {PURPOSE: To study corneal reinnervation and sensation recovery in Herpes zoster ophthalmicus (HZO). METHODS: Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis type 1 was implanted, and the explanted corneal tissues were examined by immunofluorescence histochemistry for βIII-tubulin to stain for corneal nerves. RESULTS: The initial central corneal IVCM performed in each patient showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later before undergoing surgery, case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, case 2 showed regeneration of the central subbasal nerves (4786 μm/mm) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in case 1 showed no corneal nerves, whereas case 2 showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the Boston keratoprosthesis in both patients to study innervation of the corneal transplant. Case 1 showed no nerves, whereas case 2 showed new nerves growing from the periphery into the corneal graft. CONCLUSIONS: We demonstrate that regaining corneal innervation and corneal function are possible in patients with HZO as shown by corneal sensation, IVCM, and ex vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000797},
	author = {Cruzat, Andrea and Hamrah, Pedram and Cavalcanti, Bernardo M and Zheng, Lixin and Colby, Kathryn and Pavan-Langston, Deborah}
}
@article {987951,
	title = {In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease.},
	journal = {Ocul Surf},
	volume = {15},
	number = {1},
	year = {2017},
	month = {2017 Jan},
	pages = {15-47},
	abstract = {In\&nbsp;vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in\&nbsp;vivo imaging of the cornea with images comparable to those of ex\&nbsp;vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, as well as proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2016.09.004},
	author = {Cruzat, Andrea and Qazi, Yureeda and Hamrah, Pedram}
}
@article {1698386,
	title = {A 61-Year-Old Man With Blepharoptosis, Ophthalmoplegia, Dysphagia, and Trouble Focusing His Eyes},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 May 12},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001882},
	author = {Cubero, Zoe and Chiou, Carolina A and Mukharesh, Loulwah and Rizzo, Joseph F}
}
@article {1573100,
	title = {Topical cyclosporine a (0.05\%) treatment in dry eye patients: a comparison study of Sjogren{\textquoteright}s syndrome versus non-Sjogren{\textquoteright}s syndrome},
	journal = {Int Ophthalmol},
	volume = {41},
	number = {4},
	year = {2021},
	month = {2021 Apr},
	pages = {1479-1485},
	abstract = {PURPOSE: To evaluate the clinical effect of topical cyclosporine A (CsA) (0.05\%) on dry eye patients with Sjogren{\textquoteright}s syndrome (SS) and non-Sjogren{\textquoteright}s syndrome (NSS). METHOD: This retrospective comparative study includes the dry eye (DE) patients who were treated with topical CsA. DE patients were divided into two groups as follows: DE with Sjogren{\textquoteright}s syndrome (DE-SS) and DE with Non-Sjogren{\textquoteright}s syndrome (DE-NSS). Dry eye parameters were recorded at baseline and each visit. RESULTS: Schirmer{\textquoteright}s test 1 scores were 2.7 {\textpm} 0.5\&nbsp;mm at baseline and 3.5 {\textpm} 0.7\&nbsp;mm at 12th month in DE-SS, 2.9 {\textpm} 0.7\&nbsp;mm at baseline and 9.5 {\textpm} 0.7\&nbsp;mm in DE-NSS groups at 12th month. Mean ST score was higher in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (both p = 0.001). Tear break-up time score showed a significant improvement in DE-NSS group, and it was lower in DE-NSS group than DE-SS group group at sixth and 12th months of the treatment (p = 0.044 and 0.027, respectively). Mean OSDI score was lower in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (p = 0.030 and 0.032, respectively). CONCLUSION: Topical CsA seems to be more effective in the treatment of the DE-NSS.},
	issn = {1573-2630},
	doi = {10.1007/s10792-021-01708-1},
	author = {Cubuk, Mehmet Ozgur and Ucgul, Ahmet Yucel and Ozgur, Armagan and Ozulken, Kemal and Yuksel, Erdem}
}
@article {1517197,
	title = {Comparison of widefield swept-source optical coherence tomography angiography with ultra-widefield colour fundus photography and fluorescein angiography for detection of lesions in diabetic retinopathy},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {4},
	year = {2021},
	month = {2021 Apr},
	pages = {577-581},
	abstract = {AIMS: To compare widefield swept-source optical coherence tomography angiography (WF SS-OCTA) with ultra-widefield colour fundus photography (UWF CFP) and fluorescein angiography (UWF FA) for detecting diabetic retinopathy (DR) lesions. METHODS: This prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to October 2019. Proliferative DR, non-proliferative DR and diabetic patients with no DR were included. All patients were imaged with a WF SS-OCTA using a Montage 15{\texttimes}15 mm scan. UWF CFP and UWF FA were taken by a 200{\textdegree}, single capture retinal imaging system. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), neovascularisation elsewhere (NVE), neovascularisation of the optic disc (NVD) and non-perfusion areas (NPAs). All statistical analyses were performed using SPSS V.25.0. RESULTS: One hundred and fifty-two eyes of 101 participants were included in the study. When compared with UWF CFP, WF SS-OCTA was found to be superior in detecting IRMAs (p\&lt;0.001) and NVE/NVD (p=0.007). The detection rates of MAs, IRMAs, NVE/NVD and NPAs in WF SS-OCTA were comparable with UWF FA images (p\&gt;0.05). Furthermore, when we compared WF SS-OCTA plus UWF CFP with UWF FA, the detection rates of MAs, IRMAs, NVE/NVD and NPAs were identical (p\&gt;0.005). Agreement (κ=0.916) between OCTA and FA in classifying DR was excellent. CONCLUSION: WF SS-OCTA is useful for identification of DR lesions. WF SS-OCTA plus UWF CFP may offer a less invasive alternative to FA for DR diagnosis.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316245},
	author = {Cui, Ying and Zhu, Ying and Wang, Jay C and Lu, Yifan and Zeng, Rebecca and Katz, Raviv and Vingopoulos, Filippos and Le, Rongrong and La{\'\i}ns, In{\^e}s and Wu, David M and Eliott, Dean and Vavvas, Demetrios G and Husain, Deeba and Miller, Joan W and Kim, Leo A and Miller, John B}
}
@article {1615224,
	title = {Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study},
	journal = {Ophthalmology},
	volume = {128},
	number = {9},
	year = {2021},
	month = {2021 Sep},
	pages = {1312-1324},
	abstract = {PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15\&nbsp;{\texttimes} 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth{\textquoteright}s bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24\%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95\% confidence interval [CI], 1.43-58.56; P\&nbsp;= 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95\% CI, 1.26-35.16; P\&nbsp;= 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95\% CI, 0.04-1.01; P\&nbsp;= 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95\% CI, 3.51-119.47; P \&lt; 0.001) and forward neovascularizations (hazard ratio, 9.60; 95\% CI, 2.07-68.08; P\&nbsp;=\&nbsp;0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.02.020},
	author = {Cui, Ying and Zhu, Ying and Lu, Edward S and Le, Rongrong and La{\'\i}ns, In{\^e}s and Katz, Raviv and Wang, Jay C and Garg, Itika and Lu, Yifan and Zeng, Rebecca and Eliott, Dean and Vavvas, Demetrios G and Husain, Deeba and Miller, Joan W and Kim, Leo A and Wu, David M and Miller, John B}
}
@article {1474188,
	title = {Imaging Artifacts and Segmentation Errors With Wide-Field Swept-Source Optical Coherence Tomography Angiography in Diabetic Retinopathy},
	journal = {Transl Vis Sci Technol},
	volume = {8},
	number = {6},
	year = {2019},
	month = {2019 Nov},
	pages = {18},
	abstract = {Purpose: To analyze imaging artifacts and segmentation errors with wide-field swept-source optical coherence tomography angiography (SS-OCTA) in diabetic retinopathy (DR). Methods: We conducted a prospective, observational study at Massachusetts Eye and Ear from December 2018 to March 2019. Proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), diabetic patients with no diabetic retinopathy (DR), and healthy control eyes were included. All patients were imaged with a SS-OCTA and the Montage Angio (15 {\texttimes} 9 mm) was used for analysis. Images were independently evaluated by two graders using the motion artifact score (MAS). All statistical analyses were performed using SPSS 25.0 and R software. Results: One hundred thirty-six eyes in 98 participants with the montage image were included in the study. Patients with more severe stages of DR had higher MAS by trend test analysis ( \&lt; 0.05). The occurrence of segmentation error was 0\% in the healthy group, 10.53\% in the no DR group, 10.00\% in the NPDR group, and 50\% in the PDR group. Multivariate regression analysis showed that the severity of DR and dry eye were the major factors affecting MAS ( \&lt; 0.05). There were some modifiable artifacts that could be corrected to improve image quality. Conclusions: Wide field SS-OCTA assesses retinal microvascular changes by noninvasive techniques, yet distinguishing real alterations from artifacts is paramount to accurate interpretations. DR severity and dry eye correlated with MAS. Translational Relevance: Understanding contributing factors and methods to reduce artifacts is critical to routine use and clinical trial with wide-field SS-OCTA.},
	issn = {2164-2591},
	doi = {10.1167/tvst.8.6.18},
	author = {Cui, Ying and Zhu, Ying and Wang, Jay C and Lu, Yifan and Zeng, Rebecca and Katz, Raviv and Wu, David M and Vavvas, Demetrios G and Husain, Deeba and Miller, Joan W and Kim, Leo A and Miller, John B}
}
@article {1761801,
	title = {Rapid isolation of intact retinal astrocytes: a novel approach},
	journal = {Acta Neuropathol Commun},
	volume = {11},
	number = {1},
	year = {2023},
	month = {2023 Sep 25},
	pages = {154},
	abstract = {Astrocytes are a major category of glial support cell in the central nervous system and play a variety of essential roles in both health and disease. As our understanding of the diverse functions of these cells improves, the extent of heterogeneity between astrocyte populations has emerged as a key area of research. Retinal astrocytes, which form the direct cellular environment of retinal ganglion cells somas and axons, undergo a reactive response in both human glaucoma and animal models of the disease, yet their contributions to its pathology and progression remain relatively unknown. This gap in knowledge is largely a function of inadequate isolation techniques, driven in part by the sparseness of these cells and their similarities with the more abundant retinal M{\"u}ller cells. Here, we present a novel method of isolating retinal astrocytes and enriching their RNA, tested in both normal and ocular hypertensive mice, a common model of experimental glaucoma. Our approach combines a novel enzyme assisted microdissection of retinal astrocytes with selective ribosome immunoprecipitation using the Ribotag method. Our microdissection method is rapid and preserves astrocyte morphology, resulting in a brief post-mortem interval and minimizing loss of RNA from distal regions of these cells. Both microdissection and Ribotag immunoprecipitation require a minimum of specialized equipment or reagents, and by using them in conjunction we are able to achieve \&gt; 100-fold enrichment of astrocyte RNA.},
	keywords = {Animals, Astrocytes, Central Nervous System, Ependymoglial Cells, Glaucoma, Humans, Mice, Neuroglia},
	issn = {2051-5960},
	doi = {10.1186/s40478-023-01641-7},
	author = {Cullen, Paul F and Mazumder, Arpan G and Sun, Daniel and Flanagan, John G}
}
@article {1773531,
	title = {Molecular Detection and Typing of Treponema pallidum in Non-Ocular Samples from Patients with Ocular Syphilis},
	journal = {Ocul Immunol Inflamm},
	year = {2023},
	month = {2023 Oct 05},
	pages = {1-5},
	abstract = {INTRODUCTION: Ocular syphilis is a rare but potentially sight-threatening manifestation of infection with the spirochete Treponema pallidum subspecies pallidum. Molecular strain typing of clinical specimens obtained from patients with syphilis can provide useful epidemiological and clinical information. In this study, we assess the utility of non-ocular clinical samples in strain typing for patients with diagnosed ocular syphilis. METHODS: We collected samples of excess blood, serum, and cerebrospinal fluid (CSF) from 6 patients with ocular syphilis treated in 2013-2016. DNA was extracted, purified, and then analyzed using an enhanced molecular typing method including sequence analysis of tp0548, number of repeats in the arp gene, and restriction fragment length polymorphism of the tpr gene. RESULTS: Molecular strain typing based on tp0548 gene sequence analysis revealed two cases of type F and two cases of type G in 3 of 6 (50\%) cases with CSF samples, 1 of which was obtained after starting antibiotics. In a patient with 2 distinct episodes, the same tp0548 type (type G) was identified in both episodes using different sample types (CSF, whole blood). Serum samples were available in 6 cases, but none were successfully typed with any of the methods. Amplification of the tpr and arp genes was unsuccessful in all cases. Overall, strain types were identified in 4 of the 7 episodes. CONCLUSION: Treponema pallidum strain types F and G were detected in CSF or whole blood in 4 of 7 episodes in this series. We demonstrate moderate sensitivity of strain typing in ocular syphilis using non-ocular clinical specimens.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2023.2263086},
	author = {Cummings, Olivia W and Durand, Marlene L and Barshak, Miriam B and Bispo, Paulo J M}
}
@article {1593830,
	title = {Comparison between wide-field digital imaging system and the red reflex test for universal newborn eye screening in Brazil},
	journal = {Acta Ophthalmol},
	volume = {99},
	number = {7},
	year = {2021},
	month = {2021 Nov},
	pages = {e1198-e1205},
	abstract = {PURPOSE: To compare neonatal eye screening using the red reflex test (RRT) versus the wide-field digital imaging (WFDI) system. METHODS: Prospective cohort study. Newborns (n\&nbsp;=\&nbsp;380, 760 eyes) in the Maternity Ward of Irmandade Santa Casa de Miseric{\'o}rdia de S{\~a}o Paulo hospital from May to July 2014 underwent RRT by a paediatrician and WFDI performed by the authors. Wide-field digital imaging (WFDI) images were analysed by the authors. Validity of the paediatrician{\textquoteright}s RRT was assessed by unweighted kappa [κ] statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: While WFDI showed abnormalities in 130 eyes (17.1\%), RRT was only abnormal in 13 eyes (1.7\%). Wide-field digital imaging (WFDI) detected treatable retina pathology that RRT missed including hyphema, CMV retinitis, FEVR and a vitreous haemorrhage. The sensitivity of the paediatrician{\textquoteright}s RRT to detect abnormalities was poor at 0.77\% (95\% confidence interval, CI, 0.02\%-4.21\%) with a PPV of only 7.69\% (95\% CI, 1.08\%-38.85\%). Overall, there was no agreement between screening modalities (κ\&nbsp;=\&nbsp;-0.02, 95\% CI, -0.05 to 0.01). The number needed to screen to detect ocular abnormalities using WFDI was 5.9 newborns and to detect treatable abnormalities was 76 newborns. CONCLUSION: While RRT detects gross abnormalities that preclude visualization of the retina (i.e. media opacities and very large tumours), only WFDI consistently detects subtle treatable retina and optic nerve pathology. With a higher sensitivity than the current gold standard, universal WFDI allows for early detection and management of potentially blinding ophthalmic disease missed by RRT.},
	issn = {1755-3768},
	doi = {10.1111/aos.14759},
	author = {da Cunha, Laura Pires and Cavalcante Costa, Marcelo Alexandre Agra and de Miranda, Homero Augusto and Reis Guimar{\~a}es, Juliana and Aihara, Teruo and Ludwig, Cassie A and Rosenblatt, Tatiana and Callaway, Natalia F and Pasricha, Malini and Al-Moujahed, Ahmad and Vail, Daniel and Ji, Marco H and Kumm, Jochen and Moshfeghi, Darius M}
}
@article {314126,
	title = {The role of object categories in hybrid visual and memory search},
	journal = {J Exp Psychol Gen},
	volume = {143},
	number = {4},
	year = {2014},
	month = {2014 Aug},
	pages = {1585-99},
	abstract = {In hybrid search, observers search for any of several possible targets in a visual display containing distracting items and, perhaps, a target. Wolfe (2012) found that response times (RTs) in such tasks increased linearly with increases in the number of items in the display. However, RT increased linearly with the log of the number of items in the memory set. In earlier work, all items in the memory set were unique instances (e.g., this apple in this pose). Typical real-world tasks involve more broadly defined sets of stimuli (e.g., any "apple" or, perhaps, "fruit"). The present experiments show how sets or categories of targets are handled in joint visual and memory search. In Experiment 1, searching for a digit among letters was not like searching for targets from a 10-item memory set, though searching for targets from an N-item memory set of arbitrary alphanumeric characters was like searching for targets from an N-item memory set of arbitrary objects. In Experiment 2, observers searched for any instance of N sets or categories held in memory. This hybrid search was harder than search for specific objects. However, memory search remained logarithmic. Experiment 3 illustrates the interaction of visual guidance and memory search when a subset of visual stimuli are drawn from a target category. Furthermore, we outline a conceptual model, supported by our results, defining the core components that would be necessary to support such categorical hybrid searches.},
	keywords = {Adolescent, Adult, Attention, Female, Humans, Male, Memory, Mental Recall, Reaction Time, Visual Perception, Young Adult},
	issn = {1939-2222},
	doi = {10.1037/a0036313},
	author = {Cunningham, Corbin A and Wolfe, Jeremy M}
}
@article {1504071,
	title = {Vitamin D and Ocular Inflammation},
	journal = {Ocul Immunol Inflamm},
	volume = {28},
	number = {3},
	year = {2020},
	month = {2020 04 02},
	pages = {337-340},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1734421},
	author = {Cunningham, Emmett T and Sobrin, Lucia and Hall, Anthony J and Zierhut, Manfred}
}
@article {1698326,
	title = {Electroretinographic Responses in Retinopathy of Prematurity Treated Using Intravitreal Bevacizumab or Laser},
	journal = {Am J Ophthalmol},
	volume = {252},
	year = {2023},
	month = {2023 Aug},
	pages = {275-285},
	abstract = {PURPOSE: Intravitreal injection of bevacizumab (IVB) offers advantages over laser photoablation for treatment of type 1 retinopathy of prematurity (ROP). However, retinal function has not, to date, been quantitatively compared following these interventions. Therefore, electroretinography (ERG) was used compare retinal function among eyes treated using IVB or laser, and control eyes. In addition, among the IVB-treated eyes, ERG was used to compare function in individuals in whom subsequent laser was and was not required. DESIGN: Prospective clinical cohort study. METHODS: ERG was used to record dark- and light-adapted stimulus/response functions in 21 children treated using IVB (12 of whom required subsequent laser in at least 1 eye for persistent avascular retina [PAR]). Sensitivity and amplitude parameters were derived from the a-wave, b-wave, and oscillatory potentials (OPs), representing activity in photoreceptor, postreceptor, and inner retinal cells, respectively. These parameters were then referenced to those of 76 healthy, term-born controls and compared to those of 10 children treated using laser only. RESULTS: In children with treated ROP, every ERG parameter was significantly below the mean in controls. However, these significant ERG deficits did not differ between IVB- and laser-treated eyes. Among children treated using IVB, no ERG parameter was significantly associated with dose or need for subsequent laser. CONCLUSION: Retinal function was significantly impaired in treated ROP eyes. Function in IVB-treated eyes did not differ from that in laser-treated eyes. Functional differences also did not distinguish those IVB-treated eyes that would subsequently need laser for PAR.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Child, Cohort Studies, Electroretinography, Gestational Age, Humans, Infant, Infant, Newborn, Intravitreal Injections, Laser Coagulation, Lasers, Prospective Studies, Retinopathy of Prematurity, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.04.014},
	author = {Curran, Amber-Lee K and Stukin, Justyna and Ambrosio, Lucia and Mantagos, Iason S and Wu, Carolyn and VanderVeen, Deborah K and Hansen, Ronald M and Akula, James D and Fulton, Anne B}
}
@article {1593869,
	title = {Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images},
	journal = {PLoS Genet},
	volume = {17},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {e1009497},
	abstract = {Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1009497},
	author = {Currant, Hannah and Hysi, Pirro and Fitzgerald, Tomas W and Gharahkhani, Puya and Bonnemaijer, Pieter W M and Senabouth, Anne and Hewitt, Alex W and UK Biobank Eye and Vision Consortium and International Glaucoma Genetics Consortium and Atan, Denize and Aung, Tin and Charng, Jason and Choquet, H{\'e}l{\`e}ne and Craig, Jamie and Khaw, Peng T and Klaver, Caroline C W and Kubo, Michiaki and Ong, Jue-Sheng and Pasquale, Louis R and Reisman, Charles A and Daniszewski, Maciej and Powell, Joseph E and P{\'e}bay, Alice and Simcoe, Mark J and Thiadens, Alberta A H J and van Duijn, Cornelia M and Yazar, Seyhan and Jorgenson, Eric and Macgregor, Stuart and Hammond, Chris J and Mackey, David A and Wiggs, Janey L and Foster, Paul J and Patel, Praveen J and Birney, Ewan and Khawaja, Anthony P}
}
@article {1367194,
	title = {Novel in Vitro Model for Keratoconus Disease},
	journal = {J Funct Biomater},
	volume = {3},
	number = {4},
	year = {2012},
	pages = {760-775},
	author = {Karamichos D and Zareian R and Guo X and Hutcheon AE and Ruberti JW and Zieske JD}
}
@article {1363262,
	title = {Pomalidomide is strongly antiangiogenic and teratogenic in relevant animal models},
	journal = {Proc Natl Acad Sci U S A},
	volume = {110},
	number = {50},
	year = {2013},
	month = {2013 Dec 10},
	pages = {E4818},
	keywords = {Angiogenesis Inhibitors, Animals, Neovascularization, Physiologic, Neurites, Neurotoxins, Teratogens, Thalidomide, Zebrafish},
	issn = {1091-6490},
	doi = {10.1073/pnas.1315875110},
	author = {D{\textquoteright}Amato, Robert J and Lentzsch, Suzanne and Rogers, Michael S}
}
@article {1642022,
	title = {Macrophage efferocytosis with VEGFC and lymphangiogenesis: rescuing the broken heart},
	journal = {J Clin Invest},
	volume = {132},
	number = {9},
	year = {2022},
	month = {2022 May 02},
	abstract = {Cardiac repair following ischemic injury is indispensable for survival and requires a coordinated cellular response involving the mobilization of immune cells from the secondary lymphoid organs to the site of damage. Efferocytosis, the engulfment of cell debris and dying cells by innate immune cells, along with lymphangiogenesis, the formation of new lymphatic vessels, are emerging as central to the cardiac healing response. In this issue of the JCI, Glinton et al. used state-of-the-art approaches to demonstrate that efferocytosis induced vascular endothelial growth factor C (VEGFC) in myeloid cells and stimulated lymphangiogenesis and cardiac repair. These findings provide impactful mechanistic information that can be leveraged to therapeutically target pathways in cardiac repair and ischemic heart failure.},
	keywords = {Heart, Lymphangiogenesis, Macrophages, Phagocytosis, Vascular Endothelial Growth Factor C},
	issn = {1558-8238},
	doi = {10.1172/JCI158703},
	author = {D{\textquoteright}Amore, Patricia A and Alcaide, Pilar}
}
@article {1623354,
	title = {Not Sure if You Are an Investigative Pathologist? Yes, You Are},
	journal = {Am J Pathol},
	volume = {192},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {2-3},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.11.001},
	author = {D{\textquoteright}Amore, Patricia A and Essex, Emily H and Furie, Martha B}
}
@article {1782296,
	title = {Introducing the Ocular Pathobiology Topic Category in The American Journal of Pathology},
	journal = {Am J Pathol},
	volume = {193},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1620-1621},
	keywords = {Face, Pathology, Pathology, Clinical, United States, Vision, Ocular},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2023.09.002},
	author = {D{\textquoteright}Amore, Patricia A}
}
@article {1629473,
	title = {Gerard ("Jerry") Anthony Lutty, PhD- In Memoriam (1947-2021)},
	journal = {Exp Eye Res},
	volume = {216},
	year = {2022},
	month = {2022 Jan 22},
	pages = {108949},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2022.108949},
	author = {D{\textquoteright}Amore, Patricia A and Fliesler, Steven J and Edwards, Malia M}
}
@article {1417555,
	title = {Molecular basis for the emergence of a new hospital endemic tigecycline-resistant Enterococcus faecalis ST103 lineage},
	journal = {Infect Genet Evol},
	volume = {67},
	year = {2019},
	month = {2019 Jan},
	pages = {23-32},
	abstract = {Enterococcus faecalis are a major cause of nosocomial infection worldwide, and the spread of vancomycin resistant strains (VRE) limits treatment options. Tigecycline-resistant VRE began to be isolated from inpatients at a Brazilian hospital within months following the addition of tigecycline to the hospital formulary. This was found to be the result of a spread of an ST103 E. faecalis clone. Our objective was to identify the basis for tigecycline resistance in this lineage. The genomes of two closely related tigecycline-susceptible (MIC = 0.06 mg/L), and three representative tigecycline-resistant (MIC = 1 mg/L) ST103 isolates were sequenced and compared. Further, efforts were undertaken to recapitulate the emergence of resistant strains in vitro. The specific mutations identified in clinical isolates in several cases were within the same genes identified in laboratory-evolved strains. The contribution of various polymorphisms to the resistance phenotype was assessed by trans-complementation of the wild type or mutant alleles, by testing for differences in mRNA abundance, and/or by examining the phenotype of transposon insertion mutants. Among tigecycline-resistant clinical isolates, five genes contained non-synonymous mutations, including two genes known to be related to enterococcal tigecycline resistance (tetM and rpsJ). Finally, within the in vitro-selected resistant variants, mutation in the gene for a MarR-family response regulator was associated with tigecycline resistance. This study shows that E. faecalis mutates to attain tigecycline resistance through the complex interplay of multiple mechanisms, along multiple evolutionary trajectories.},
	issn = {1567-7257},
	doi = {10.1016/j.meegid.2018.10.018},
	author = {Dabul, Andrei Nicoli Gebieluca and Avaca-Crusca, Juliana Sposto and Navais, Roberto Barranco and Merlo, Tha{\'\i}s Panhan and Van Tyne, Daria and Gilmore, Michael S and Camargo, Ilana Lopes Baratella da Cunha}
}
@article {1319463,
	title = {Resistance in In Vitro Selected Tigecycline-Resistant Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Is Driven by Mutations in mepR and mepA Genes},
	journal = {Microb Drug Resist},
	volume = {24},
	number = {5},
	year = {2018},
	month = {2018 Jun},
	pages = {519-526},
	abstract = {A tigecycline-susceptible (TGC-S) Sequence Type (ST) 5 clinical methicillin-resistant Staphylococcus aureus (MRSA) strain was cultured in escalating levels of tigecycline, yielding mutants eightfold more resistant. Their genomes were sequenced to identify genetic alterations, resulting in resistance. Alterations in rpsJ, commonly related to tigecycline resistance, were also investigated. Tigecycline resistance was mediated by loss-of-function mutations in the transcriptional repressor mepR, resulting in derepression of the efflux pump mepA. Increased levels of resistance were obtained by successive mutations in mepA itself. No alterations in RpsJ were observed in selected strains, but we observed a K57M substitution, previously correlated with resistance, among TGC-S clinical strains. Thus, the pathway to tigecycline resistance in CC5 MRSA in vitro appears to be derepression of mep operon as the result of mepR loss-of-function mutation, followed by alterations in MepA efflux pump. This shows that other evolutionary pathways, besides mutation of rpsJ, are available for evolving tigecycline resistance in CC5 MRSA.},
	issn = {1931-8448},
	doi = {10.1089/mdr.2017.0279},
	author = {Dabul, Andrei Nicoli Gebieluca and Avaca-Crusca, Juliana Sposto and Van Tyne, Daria and Gilmore, Michael S and Camargo, Ilana Lopes Baratella Cunha}
}
@article {1016026,
	title = {The Increased Transforming Growth Factor-β Signaling Induced by Diabetes Protects Retinal Vessels},
	journal = {Am J Pathol},
	volume = {187},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {627-638},
	abstract = {The roles of transforming growth factor (TGF)-β in extracellular matrix production and vascular remodeling, coupled with increased TGF-β expression and signaling in diabetes, suggest TGF-β as an important contributor to the microangiopathy of diabetic retinopathy and nephropathy. To investigate whether increased TGF-β signaling could be a therapeutic target for preventing retinopathy, we used a pharmacologic approach (SM16, a selective inhibitor of the type 1 TGF-β receptor activin receptor-like kinase 5, orally active) to inhibit the increased, but not the basal, Tgf-β signaling in retinal vessels of diabetic rats. At the level of vascular gene expression, 3.5 months{\textquoteright} diabetes induced minimal changes. Diabetes + SM16 for 3 weeks caused widespread changes in gene expression poised to enhance vascular inflammation, thrombosis, leakage, and wall instability; these changes were not observed in control rats\&nbsp;given SM16. The synergy of diabetes and SM16 in altering gene expression was not observed in the lung. At the level of vascular network morphology, 7 months{\textquoteright} diabetes induced no detectable changes. Diabetes + SM16 for 3 weeks caused instead distorted morphology and decreased density. Thus, in\&nbsp;diabetes, retinal vessels become dependent on a small increase in TGF-β signaling via activin receptor-like kinase 5 to maintain early integrity. The increased TGF-β signaling may protect against rapid retinopathy progression and should not be a target of inhibitory interventions.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2016.11.007},
	author = {Dagher, Zeina and Chiara Gerhardinger and Vaz, Joseph and Goodridge, Michael and Tecilazich, Francesco and Lorenzi, Mara}
}
@article {1364596,
	title = {Associated signs, demographic characteristics, and management of dacryocystocele in 64 infants},
	journal = {J AAPOS},
	volume = {16},
	number = {3},
	year = {2012},
	month = {2012 Jun},
	pages = {255-60},
	abstract = {PURPOSE: To describe the incidence of associated infection, respiratory compromise, apparent intranasal cyst, as well as sex, laterality, and age at presentation in 64 infants with dacryocystocele and to assess characteristics associated with successful interventions. METHODS: A retrospective chart review of all patients with dacryocystocele seen at Children{\textquoteright}s Hospital Boston between 1996 and 2010 was performed. Inclusion criteria were accuracy of diagnosis, treatment, and follow-up at our institution. Interventions were divided into 3 categories: procedures that did not require general anesthesia; simple procedures requiring general anesthesia, such as nasolacrimal probing with or without stent or balloon dilation; and more complex procedures under general anesthesia, specifically, those aided by intranasal endoscopy. RESULTS: Of the 90 identified patients, 64 met inclusion criteria. The majority of patients were female (63\%) and had unilateral involvement (77\%). More than one-half of all patients were successfully treated without anesthesia; however, patients presenting with infection were more likely to be treated with a simple procedure under general anesthesia. All patients treated endoscopically had intranasal cysts. Age, sex, and infection did not predict the use of intranasal endoscopy. Bilaterality of dacryocystocele was associated with the use of an endoscopic approach. CONCLUSIONS: Many infants with dacryocystocoele can be successfully treated without general anesthesia. The incidence of occult intranasal cyst among those treated without endoscopy remains unknown. Patients who were treated under general anesthesia but without the use of nasal endoscopy were more likely to have an infected system, but the clinical significance of this association is not clear.},
	keywords = {Anesthesia, General, Catheterization, Endoscopy, Female, Humans, Incidence, Infant, Infant, Newborn, Lacrimal Apparatus Diseases, Male, Mucocele, Nasolacrimal Duct, Ophthalmologic Surgical Procedures, Retrospective Studies, Stents, Tomography, X-Ray Computed},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2012.01.004},
	author = {Dagi, Linda R and Bhargava, Ankit and Melvin, Patrice and Prabhu, Sanjay P}
}
@article {1043226,
	title = {Rectus muscle excyclorotation and V-pattern strabismus: a quantitative appraisal of clinical relevance in syndromic craniosynostosis},
	journal = {Br J Ophthalmol},
	volume = {101},
	number = {11},
	year = {2017},
	month = {2017 Nov},
	pages = {1560-1565},
	abstract = {PURPOSE: V-pattern strabismus observed with syndromic craniosynostosis has been attributed to disparate causes. We compared severity of V pattern with degree of excyclorotation of rectus muscles to appraise significance of this proposed aetiology. METHODS: 43 patients with Apert, Crouzon or Pfeiffer syndrome referred to Boston Children{\textquoteright}s Hospital Department of Ophthalmology were identified. 28 met inclusion criteria for retrospective cohort study, specifically: (1) sensorimotor measurements in minimum of seven cardinal gazes, (2) quantified fundus torsion and (3) orbital CT imaging sufficient to measure rectus muscle cyclorotation in coronal and quasicoronal planes, posteriorly (near orbital apex) and anteriorly (near pulleys). Patients were placed in one of four V-pattern severity groups. The most severe group demonstrated inability to elevate abducted eye above midline with characteristic {\textquoteright}seesaw{\textquoteright} misalignment during horizontal saccades. Rectus muscle cyclorotation was measured by paediatric neuroradiologist blinded to group placement. Primary outcome was correlation of severity of V pattern with degree of excyclorotation. Secondary outcome was correlation of severity with craniosynostosis syndrome. RESULTS: Increasing severity of V pattern correlated with greater excyclorotation in anterior coronal (p=0.009), anterior quasicoronal (p=0.021), posterior coronal (p=0.014) and posterior quasicoronal (p=0.040) planes for moderate-to-severe V pattern. Even greater excyclorotation was associated with seesaw V pattern in anterior quasicoronal (p=0.004) and posterior quasicoronal (p=0.001) views. Highly significant association was found between Apert syndrome and severity of V pattern (p=0.004). CONCLUSIONS: Severity of V pattern is associated with magnitude of excyclorotation. More severe V pattern and seesaw strabismus noted with Apert syndrome may relate to distinctive orbital morphology.},
	keywords = {Child, Preschool, Craniosynostoses, Eye Movements, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Oculomotor Muscles, Retrospective Studies, Severity of Illness Index, Strabismus, Syndrome, Tomography, X-Ray Computed, Vision, Binocular},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2016-309996},
	author = {Dagi, Linda R and MacKinnon, Sarah and Zurakowski, David and Prabhu, Sanjay P}
}
@article {1511504,
	title = {Age at Craniosynostosis Surgery and Its Impact on Ophthalmologic Diagnoses: A Single-Center Retrospective Review},
	journal = {Plast Reconstr Surg},
	volume = {146},
	number = {3},
	year = {2020},
	month = {2020 09},
	pages = {375e-376e},
	keywords = {Craniosynostoses, Humans, Retrospective Studies},
	issn = {1529-4242},
	doi = {10.1097/PRS.0000000000007111},
	author = {Dagi, Linda R and Rogers, Gary F and Proctor, Mark R and Meara, John G}
}
@article {1359923,
	title = {Commentary: Ernest Codman and the Impact of Quality Improvement in Neurosurgery: A Century Since the Idea of the "End Result"},
	journal = {Neurosurgery},
	volume = {84},
	number = {2},
	year = {2019},
	month = {2019 Feb 01},
	pages = {E120-E121},
	issn = {1524-4040},
	doi = {10.1093/neuros/nyy526},
	author = {Dagi, T Forcht and Dagi, Linda R}
}
@article {1806546,
	title = {Adult Strabismus Preferred Practice Pattern{\textregistered}},
	journal = {Ophthalmology},
	year = {2024},
	month = {2024 Feb 12},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.12.040},
	author = {Dagi, Linda R and Velez, Federico G and Holmes, Jonathan M and Archer, Steven M and Strominger, Mitchell B and Pineles, Stacy L and Paysse, Evelyn A and Pihlblad, Matthew Simon and Atalay, Hatice Tuba and Campolattaro, Brian N and Chang, Yoon-Hee and American Academy of Ophthalmology Preferred Practice Pattern Adult Strabismus Panel}
}
@article {341666,
	title = {Using spectral-domain optical coherence tomography to detect optic neuropathy in patients with craniosynostosis.},
	journal = {J AAPOS},
	volume = {18},
	number = {6},
	year = {2014},
	month = {2014 Dec},
	pages = {543-9},
	abstract = {BACKGROUND: Detecting and monitoring optic neuropathy in patients with craniosynostosis is a clinical challenge due to limited cooperation, and subjective measures of visual function. The purpose of this study was to appraise the correlation of peripapillary retinal nerve fiber layer (RNFL) thickness measured by spectral-domain ocular coherence tomography (SD-OCT) with indication of optic neuropathy based on fundus examination. METHODS: The medical records of all patients with craniosynostosis presenting for ophthalmic evaluation during 2013 were retrospectively reviewed. The following data were abstracted from the record: diagnosis, historical evidence of elevated intracranial pressure, current ophthalmic evaluation and visual field results, and current peripapillary RNFL thickness. RESULTS: A total of 54 patients were included (mean age, 10.6\&nbsp;years [range, 2.4-33.8\&nbsp;years]). Thirteen (24\%) had evidence of optic neuropathy based on current fundus examination. Of these, 10 (77\%) demonstrated either peripapillary RNFL elevation and papilledema or depression with optic atrophy. Sensitivity for detecting optic atrophy was 88\%; for papilledema, 60\%; and for either form of optic neuropathy, 77\%. Specificity was 94\%, 90\%, and 83\%, respectively. Kappa agreement was substantial for optic atrophy (κ\&nbsp;=\&nbsp;0.73) and moderate for papilledema (κ\&nbsp;=\&nbsp;0.39) and for either form of optic neuropathy (κ\&nbsp;=\&nbsp;0.54). Logistic regression indicated that peripapillary RNFL thickness was predictive of optic neuropathy (P\&nbsp;\&lt;\&nbsp;0.001). Multivariable analysis demonstrated that RNFL thickness measurements were more sensitive at detecting optic neuropathy than visual field testing (likelihood ratio\&nbsp;=\&nbsp;10.02; P\&nbsp;=\&nbsp;0.002). Sensitivity and specificity of logMAR visual acuity in detecting optic neuropathy were 15\% and 95\%, respectively. CONCLUSIONS: Peripapillary RNFL thickness measured by SD-OCT provides adjunctive evidence for identifying optic neuropathy in patients with craniosynostosis and appears more sensitive at detecting optic atrophy than papilledema.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2014.07.177},
	author = {Dagi, Linda R and Tiedemann, Laura M and Heidary, Gena and Robson, Caroline D and Hall, Amber M and Zurakowski, David}
}
@article {1483625,
	title = {Adult Strabismus Preferred Practice Pattern{\textregistered}},
	journal = {Ophthalmology},
	volume = {127},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {P182-P298},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.09.023},
	author = {Dagi, Linda R and Velez, Federico G and Archer, Steven M and Atalay, Hatice Tuba and Campolattaro, Brian N and Holmes, Jonathan M and Kerr, Natalie C and Kushner, Burton J and MacKinnon, Sarah E and Paysse, Evelyn A and Pihlblad, Matthew Simon and Pineles, Stacy L and Strominger, Mitchell B and Stager, David R and Stager, David and Capo, Hilda}
}
@article {1532372,
	title = {Adjustable graded augmentation of superior rectus transposition for treatment of abducens nerve palsy and Duane syndrome},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Sep 22},
	abstract = {PURPOSE: To report the results of adjustable graded augmentation of superior rectus transposition, a novel modification of superior rectus transposition (SRT) designed to reduce postoperative vertical or torsional diplopia. METHODS: The medical records of patients who underwent adjustable graded augmentation of SRT with or without adjustable medial rectus recession (MRc) from February 2017 to December 2019 were reviewed retrospectively. A Mendez ring was used to monitor torsional change after transposition of the superior rectus muscle to the lateral rectus muscle and after sequential placement of 2 or 3 augmentation sutures by superior rectus-lateral rectus loop myopexy. If excessive mechanical intorsion was induced, the responsible augmentation suture was severed intraoperatively. If torsional or vertical diplopia was noted after recovery, the distal-most augmentation suture was cut. Exotropia was managed by severing the distal-most augmentation suture or by medial rectus adjustment. RESULTS: A total of 8 patients who underwent adjustable graded augmentation of SRT were included (6 using the 3-suture technique): 3 for esotropic Duane syndrome, 2 for abducens nerve palsy, 1 for Moebius syndrome, and 2 for combined trochlear and abducens nerve palsies. Of the 8 patients, 4 had prior strabismus surgery, and 1 patient had previously undergone treatment with botulinum toxin. Severing one augmentation suture in 3 cases resolved vertical (n = 2) or torsional (n = 1) diplopia and consecutive exotropia (n = 1), resulting in excellent alignment and reduction of torticollis to \&lt;4{\textdegree} in 7 cases. The technique proved insufficient in 1 patient, who had undergone 3 prior strabismus procedures. CONCLUSIONS: In this study cohort, adjustable graded augmentation of SRT effectively managed the risk of postoperative vertical or torsional diplopia.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.05.013},
	author = {Dagi, Linda R and Elhusseiny, Abdelrahman M}
}
@article {959391,
	title = {Conjunctival Melanoma Responsive to Combined Systemic BRAF/MEK Inhibitors},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {5},
	year = {2017},
	month = {2017 Sep/Oct},
	pages = {e114-e116},
	abstract = {This report demonstrates a unique case of conjunctival melanoma harboring a BRAF V600E mutation responsive to systemic therapy with BRAF and MEK inhibitors. While systemic therapy would not be appropriate in patients with local disease alone, it may act therapeutically in cases of higher stage ocular surface and eyelid melanoma.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000833},
	author = {Dagi Glass, Lora R and Lawrence, Donald P and Jakobiec, Frederick A and Freitag, Suzanne K}
}
@article {913421,
	title = {Large upper eyelid coloboma repair: a one-stage, one-site technique.},
	journal = {J AAPOS},
	year = {2016},
	month = {2016 Sep 21},
	abstract = {Current techniques for repairing large eyelid colobomas require preparation of other tissue sites and occasionally more than one procedure. We present a technique that requires only one procedure and is limited to the colobomatous eyelid; in addition, it is specifically designed to help avoid postoperative astigmatic and obstructive amblyopia. Outcomes are demonstrated in 3 cases of hemifacial microsomia. Large colobomas on the upper eyelid can be successfully and aesthetically repaired with only one procedure, incising only the congenitally abnormal eyelid.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2016.05.018},
	author = {Dagi Glass, Lora R and Elliott, Alexandra T}
}
@article {591261,
	title = {Orbital Complication Following Calcium Hydroxylapatite Filler Injection.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 Oct 30},
	abstract = {Cosmetic facial fillers have gained immense popularity in recent years. Although some patients opt to undergo an injection over surgery in light of the risks of an operation, there have been numerous reports of complications from these injections, including blindness. It is thought that filler particles can migrate within an artery and become emboli within small vessels. This case of focal orbital inflammation and dysmotility as a consequence of calcium hydroxylapatite filler injection in the face has not yet been documented in the literature.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000584},
	author = {Dagi Glass, Lora R and Choi, Catherine J and Lee, Nahyoung Grace}
}
@article {1043221,
	title = {Reply re: Dr. Kubota{\textquoteright}s Letter to the Editor, "Corticosteroids or biopsy for idiopathic orbital inflammation"},
	journal = {Surv Ophthalmol},
	volume = {62},
	number = {2},
	year = {2017},
	month = {2017 Mar - Apr},
	pages = {255},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.10.006},
	author = {Dagi Glass, Lora R and Freitag, Suzanne K}
}
@article {1586156,
	title = {Artificial Intelligence (AI) and Retinal Optical Coherence Tomography (OCT)},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {341-345},
	abstract = {Ophthalmology has been at the forefront of medical specialties adopting artificial intelligence. This is primarily due to the "image-centric"\&nbsp;nature of the field. Thanks to the abundance of patients{\textquoteright} OCT scans, analysis of OCT imaging has greatly benefited from artificial intelligence to expand patient screening and facilitate clinical decision-making.In this review, we define the concepts of artificial intelligence, machine learning, and deep learning and how different artificial intelligence algorithms have been applied in OCT image analysis for disease screening, diagnosis, management, and prognosis.Finally, we address some of the challenges and limitations that might affect the incorporation of artificial intelligence in ophthalmology. These limitations mainly revolve around the quality and accuracy of datasets used in the algorithms and their generalizability, false negatives, and the cultural challenges around the adoption of the technology.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1901123},
	author = {Dahrouj, Mohammad and Miller, John B}
}
@article {1359924,
	title = {Sudden-Onset Unilateral Macular Hemorrhage in a Middle-aged Man},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {11},
	year = {2018},
	month = {2018 Nov 01},
	pages = {1301-1302},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.1095},
	author = {Dahrouj, Mohammad and Oellers, Patrick and Wu, David M}
}
@article {1363263,
	title = {Efficacy of surgical simulator training versus traditional wet-lab training on operating room performance of ophthalmology residents during the capsulorhexis in cataract surgery},
	journal = {J Cataract Refract Surg},
	volume = {39},
	number = {11},
	year = {2013},
	month = {2013 Nov},
	pages = {1734-41},
	abstract = {PURPOSE: To compare the operating room performance of ophthalmology residents trained by traditional wet-lab versus surgical simulation on the continuous curvilinear capsulorhexis (CCC) portion of cataract surgery. SETTING: Academic tertiary referral center. DESIGN: Prospective randomized study. METHODS: Residents who chose to participate and provided informed consent were randomized to preoperative CCC training in the wet lab or on a simulator. Residents completed pre-practice demographic questionnaires including habits of daily living. After completion of their preoperative training (wet lab versus simulator), residents performed their first CCC of the clinical rotation under the direct supervision of an attending physician as part of their standard training at the facility. Residents then completed satisfaction questionnaires regarding their preoperative training. Two attending surgeons reviewed and graded each video of operating room performance. The mean score between the 2 attending physicians was used as the individual performance score for each of the 12 performance criteria. The overall score was calculated as the sum of these 12 individual performance scores (standardized). RESULTS: Ten residents trained in the wet lab and 11 on the simulator. There was no significant difference in overall score between the 2 groups (P=.608). There was no significant difference in any individual score except time (wet-lab group faster than simulator group) (P=.038). CONCLUSIONS: Preoperative simulator training prepared residents for the operating room as effectively as the wet lab. The time to pass the simulator curriculum was predictive of the time and overall performance in the operating room. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.},
	keywords = {Academic Medical Centers, Capsulorhexis, Cataract Extraction, Clinical Competence, Computer Simulation, Computer-Assisted Instruction, Education, Medical, Graduate, Educational Measurement, Humans, Internship and Residency, Models, Anatomic, Operating Rooms, Ophthalmology, Prospective Studies, Video Recording},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2013.05.044},
	author = {Daly, Mary K and Gonzalez, Efren and Siracuse-Lee, Donna and Legutko, Paul A}
}
@article {1351155,
	title = {Transscleral delivery of Nd: YLF laser at 1,047 nm causes vascular occlusion in experimental pigmented choroidal melanoma},
	journal = {Retina},
	volume = {34},
	number = {4},
	year = {2014},
	month = {2014 Apr},
	pages = {792-800},
	abstract = {PURPOSE: The aims of this study were to determine the scleral attenuation of focused neodymium: yttrium-lanthanum-fluoride laser at 1,047 nm applied transsclerally and whether transscleral delivery can close the vascular supply at the base of experimental choroidal melanoma in rabbits. METHODS: Fifty-two New Zealand albino rabbits were included. Scleral laser attenuation was measured across fresh sclera. B16F10 melanomas were established in the subchoroidal space of 49 rabbits. Twenty-one animals were killed immediately after transscleral treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were performed before treatment, immediately after, and weekly during the follow-up. Eyes were examined by light microscopy. RESULTS: Sclera attenuated laser energy by 31\% {\textpm} 7\%. Immediately after treatment, angiography showed diffuse hypofluorescence in 71\% (15 of 21 rabbits). Light microscopy showed vascular occlusion extending at least two thirds of the tumor thickness from the base. Seven of the 14 tumors followed for 15 days {\textpm} 8 days were eradicated. There was no correlation between tumor height and eradication. CONCLUSION: Rabbit sclera attenuated 31\% {\textpm} 7\% of laser energy. A single transscleral treatment causes tumor vascular closure at the base and may serve as an adjuvant therapy to ensure destruction of deep and intrascleral tumor cells.},
	keywords = {Animals, Choroid Neoplasms, Female, Fluorescein Angiography, Laser Coagulation, Lasers, Solid-State, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, Ophthalmoscopy, Rabbits, Sclera, Tumor Cells, Cultured},
	issn = {1539-2864},
	doi = {10.1097/IAE.0b013e3182a2e723},
	author = {Damico, Francisco Max and Takahashi, Beatriz S and Acquesta, Felipe B}
}
@article {1363264,
	title = {On the edge: the clinician-scientist in ophthalmology},
	journal = {JAMA Ophthalmol},
	volume = {131},
	number = {11},
	year = {2013},
	month = {2013 Nov},
	pages = {1401-2},
	keywords = {Biomedical Research, Humans, Ophthalmology, Physicians},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.4883},
	author = {Dana, Reza and Miller, Joan W}
}
@article {1304380,
	title = {A New Frontier in Curing Corneal Blindness},
	journal = {N Engl J Med},
	volume = {378},
	number = {11},
	year = {2018},
	month = {2018 03 15},
	pages = {1057-1058},
	keywords = {Blindness, Cornea, Corneal Diseases},
	issn = {1533-4406},
	doi = {10.1056/NEJMe1800726},
	author = {Dana, Reza}
}
@article {1615216,
	title = {Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy},
	journal = {BMC Ophthalmol},
	volume = {21},
	number = {1},
	year = {2021},
	month = {2021 Sep 08},
	pages = {327},
	abstract = {BACKGROUND: Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed. METHODS: An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations. RESULTS: There was agreement on 94\% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK. CONCLUSIONS: These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.},
	keywords = {Consensus, Cornea, Corneal Dystrophies, Hereditary, Humans, Keratitis, Trigeminal Nerve Diseases},
	issn = {1471-2415},
	doi = {10.1186/s12886-021-02092-1},
	author = {Dana, Reza and Farid, Marjan and Gupta, Preeya K and Hamrah, Pedram and Karpecki, Paul and McCabe, Cathleen M and Nijm, Lisa and Pepose, Jay S and Pflugfelder, Stephen and Rapuano, Christopher J and Saini, Arvind and Gibbs, Sarah N and Broder, Michael S}
}
@article {1424801,
	title = {Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System},
	journal = {Am J Ophthalmol},
	volume = {202},
	year = {2019},
	month = {2019 Jun},
	pages = {47-54},
	abstract = {PURPOSE: To assess overall prevalence, annual prevalence, and incidence of dry eye disease (DED) in a large, representative population in the United States. DESIGN: Prevalence and incidence study. METHODS: Retrospective analysis using the Department of Defense (DOD) Military Health System (MHS) data on beneficiary medical claims from United States DOD military and civilian facilities, January 1, 2003 through March 31, 2015. PATIENT POPULATION: Using an algorithm, medical diagnostic codes indicative of DED and prescriptions for cyclosporine ophthalmic emulsion identified a DED population from 9.7 million MHS beneficiaries (DOD service members, retirees, and dependents, aged 2-80+ years). MAIN OUTCOME MEASURES: DED overall prevalence (2003-2015), annual prevalence (2005-2012), and annual incidence (2008-2012) stratified by sex, age group, and International Statistical Classification of Diseases and Related Health Problems, Ninth Revision diagnosis code grouping. RESULTS: DED prevalence was 5.28\% overall, 7.78\% among female beneficiaries, 2.96\% among male beneficiaries and increased with age from 0.20\% for ages 2-17 years, to 11.66\% for individuals aged 50+ years. Annual prevalence increased from 0.8\% to 3.0\% overall, from 1.4\% to 4.5\% in female beneficiaries, and from 0.3\% to 1.6\% in male beneficiaries. Annual prevalence increased across age groups starting at age 18-39, 0.1\%-0.6\%, to age 50+, 1.8\%-6.0\%. Annual incidence increased from 0.6\% to 0.9\% overall, from 0.8\% to 1.2\% in female beneficiaries, and from 0.3\% to 0.6\% in male beneficiaries. Across age groups, annual incidence increased starting at age 18-39 (0.2\%-0.3\%), to age 50+ (1.0\%-1.6\%). CONCLUSIONS: DED overall prevalence, annual prevalence, and incidence were found to increase over time for all demographics. These findings highlight the continued importance of research and therapeutic development for this common condition.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.01.026},
	author = {Dana, Reza and Bradley, John L and Guerin, Annie and Pivneva, Irina and Stillman, Ipek {\"O}zer and Evans, Amber M and Schaumberg, Debra A}
}
@article {1645452,
	title = {The Prevalence of Retinal Disease and Associated CNS Disease in Young Patients with Incontinentia Pigmenti},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {1113-1121},
	abstract = {PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September\&nbsp;2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0\&nbsp;= no disease, 1\&nbsp;= vascular abnormalities without leakage, 2\&nbsp;= leakage or neovascularization, and 3\&nbsp;= retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51\%) by indirect ophthalmoscopy and 26 of 35 patients (74\%) by FA (P\&nbsp;= 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29\%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z\&nbsp;= -2.12, P\&nbsp;= 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.},
	keywords = {Central Nervous System Diseases, Child, Humans, Incontinentia Pigmenti, Infant, Prevalence, Retina, Retinal Diseases, Retrospective Studies},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.05.032},
	author = {Danford, Ian D and Scruggs, Brittni A and Capone, Antonio and Trese, Michael T and Drenser, Kim A and Thanos, Aristomenis and Nudleman, Eric and Amphornphruet, Atchara and Tipsuriyaporn, Boontip and Hubbard, G Baker and Ells, Anna and Harper, C Armitage and Goldstein, Jessica and Calvo, Charles and Wallace-Carrete, Chris and Berry, Duncan and Chang, Emmanuel and Leishman, Lisa and Shapiro, Michael and Blair, Michael and Mikhail, Mikel and Shields, Carol L and Schwendeman, Rachel and Yonekawa, Yoshihiro and Gupta, Mrinali P and Orlin, Anton and Prakhunhungsit, Supalert and Mukai, Shizuo and Berrocal, Audina and Hartnett, M Elizabeth and Campbell, J Peter}
}
@article {1059751,
	title = {Risk of Ocular Hypertension in Adults with Noninfectious Uveitis},
	journal = {Ophthalmology},
	volume = {124},
	number = {8},
	year = {2017},
	month = {2017 Aug},
	pages = {1196-1208},
	abstract = {PURPOSE: To describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis. DESIGN: Retrospective, multicenter, cohort study. PARTICIPANTS: Patients aged >=18 years with noninfectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics. METHODS: Demographic, ocular, and treatment data were extracted from medical records of uveitis cases. MAIN OUTCOME MEASURES: Prevalent and incident OHT with intraocular pressures (IOPs) of >=21 mmHg, >=30 mmHg, and increase of >=10 mmHg from documented IOP recordings (or use of treatment for OHT). RESULTS: Among 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT >=21 mmHg and OHT >=30 mmHg are 14.4\% (95\% confidence interval [CI], 13.4-15.5) and 5.1\% (95\% CI, 4.7-5.6) per year, respectively. Statistically significant risk factors for incident OHT >=30 mmHg included systemic hypertension (adjusted hazard ratio [aHR], 1.29); worse presenting visual acuity (<=20/200 vs. >=20/40, aHR, 1.47); pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP >=21 mmHg (aHR, 2.68), >=30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and >=2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior synechiae (aHR, 1.81); current use of prednisone \&gt;7.5 mg/day (aHR, 1.86); periocular corticosteroids in the last 3 months (aHR, 2.23); current topical corticosteroid use [>=8{\texttimes}/day vs. none] (aHR, 2.58); and prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT. CONCLUSIONS: Ocular hypertension is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with 1 or more of the several risk factors identified are at particularly high risk and must be carefully managed. Modifiable risk factors, such as use of corticosteroids, suggest opportunities to reduce OHT risk within the constraints of the overriding need to control the primary ocular inflammatory disease.},
	keywords = {Adolescent, Adult, Aged, Cohort Studies, Female, Glucocorticoids, Humans, Incidence, Intraocular Pressure, Male, Middle Aged, Ocular Hypertension, Prevalence, Retrospective Studies, Risk Assessment, Risk Factors, Uveitis, Visual Acuity, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.03.041},
	author = {Daniel, Ebenezer and Pistilli, Maxwell and Kothari, Srishti and Khachatryan, Naira and Ka{\c c}maz, R Oktay and Gangaputra, Sapna S and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Foster, C Stephen and Jabs, Douglas A and Nussenblatt, Robert B and Rosenbaum, James T and Levy-Clarke, Grace A and Bhatt, Nirali P and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases Research Group}
}
@article {1532327,
	title = {Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity},
	journal = {J Mol Med (Berl)},
	volume = {98},
	number = {11},
	year = {2020},
	month = {2020 Nov},
	pages = {1639-1656},
	abstract = {Fibulin-3 (F3) is an extracellular matrix glycoprotein found in basement membranes across the body. An autosomal dominant R345W mutation in F3 causes a macular dystrophy resembling dry age-related macular degeneration (AMD), whereas genetic removal of wild-type (WT) F3 protects mice from sub-retinal pigment epithelium (RPE) deposit formation. These observations suggest that F3 is a protein which can regulate pathogenic sub-RPE deposit formation in the eye. Yet the precise role of WT F3 within the eye is still largely unknown. We found that F3 is expressed throughout the mouse eye (cornea, trabecular meshwork (TM) ring, neural retina, RPE/choroid, and optic nerve). We next performed a thorough structural and functional characterization of each of these tissues in WT and homozygous (F3) knockout mice. The corneal stroma in F3 mice progressively thins beginning at 2 months, and the development of corneal opacity and vascularization starts at 9 months, which worsens with age. However, in all other tissues (TM, neural\&nbsp;retina, RPE, and optic nerve), gross structural anatomy and functionality were similar across WT and F3 mice when evaluated using SD-OCT, histological analyses, electron microscopy, scotopic electroretinogram, optokinetic response, and axonal anterograde transport. The lack of noticeable retinal abnormalities in F3 mice was confirmed in a human patient with biallelic loss-of-function mutations in F3. These data suggest that (i) F3 is important for maintaining the structural integrity of the cornea, (ii) absence of F3 does not affect the structure or function of any other ocular tissue in which it is expressed, and (iii) targeted silencing of F3 in the retina\&nbsp;and/or RPE will likely be well-tolerated, serving as a\&nbsp;safe therapeutic strategy for reducing sub-RPE deposit formation in disease. KEY MESSAGES: {\textbullet} Fibulins are expressed throughout the body at varying levels. {\textbullet} Fibulin-3 has a tissue-specific pattern of expression within the eye. {\textbullet} Lack of fibulin-3 leads to structural deformities in the cornea. {\textbullet} The retina and RPE remain structurally and functionally healthy in the absence of fibulin-3 in both mice and humans.},
	issn = {1432-1440},
	doi = {10.1007/s00109-020-01974-z},
	author = {Daniel, Steffi and Renwick, Marian and Chau, Viet Q and Datta, Shyamtanu and Maddineni, Prabhavathi and Zode, Gulab and Wade, Emma M and Robertson, Stephen P and Petroll, W Matthew and Hulleman, John D}
}
@article {1364597,
	title = {High throughput mass spectrometry-based mutation profiling of primary uveal melanoma},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {11},
	year = {2012},
	month = {2012 Oct 09},
	pages = {6991-6},
	abstract = {PURPOSE: We assessed for mutations in a large number of oncogenes and tumor suppressor genes in primary uveal melanomas using a high-throughput profiling system. METHODS: DNA was extracted and purified from 134 tissue samples from fresh-frozen tissues (n = 87) or formalin-fixed, paraffin-embedded tissues (n = 47) from 124 large uveal melanomas that underwent primary treatment by enucleation. DNA was subjected to whole genome amplification and MALDI-TOF mass spectrometry-based mutation profiling (\&gt;1000 mutations tested across 120 oncogenes and tumor suppressor genes) using the OncoMap3 platform. All candidate mutations, as well as commonly occurring mutations in GNAQ and GNA11, were validated using homogeneous mass extension (hME) technology. RESULTS: Of 123 samples, 97 (79\%, representing 89 unique tumors) were amplified successfully, passed all quality control steps, and were assayed with the OncoMap platform. A total of 58 mutation calls was made for 49 different mutations across 26 different genes in 34/98 (35\%) samples. Of 91 tumors that underwent hME validation, 83 (91\%) harbored mutations in the GNAQ (47\%) or GNA11 (44\%) genes, while hME validation revealed two tumors with mutations in EGFR. These additional mutations occurred in tumors that also had mutations in GNAQ or GNA11. CONCLUSIONS: The vast majority of primary large uveal melanomas harbor mutually-exclusive mutations in GNAQ or GNA11, but very rarely have the oncogenic mutations that are reported commonly in other cancers. When present, these other mutations were found in conjunction with GNAQ/GNA11 mutations, suggesting that these other mutations likely are not the primary drivers of oncogenesis in uveal melanoma.},
	keywords = {DNA Mutational Analysis, DNA, Neoplasm, Gene Amplification, Gene Expression Profiling, GTP-Binding Protein alpha Subunits, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, Melanoma, Mutation, Oncogenes, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tumor Suppressor Proteins, Uveal Neoplasms},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-10427},
	author = {Daniels, Anthony B and Lee, Joo-Eun and MacConaill, Laura E and Palescandolo, Emanuele and van Hummelen, Paul and Adams, Scott M and Deangelis, Margaret M and Hahn, William C and Gragoudas, Evangelos S and Harbour, J William and Garraway, Levi A and Kim, Ivana K}
}
@article {1364598,
	title = {Genotype-phenotype correlations in Bardet-Biedl syndrome},
	journal = {Arch Ophthalmol},
	volume = {130},
	number = {7},
	year = {2012},
	month = {2012 Jul},
	pages = {901-7},
	abstract = {OBJECTIVE: To determine whether mutations in different Bardet-Biedl syndrome (BBS) genes result in different ocular phenotypes. METHODS: Thirty-seven patients from 31 families were enrolled who met the clinical criteria for BBS and for whom a BBS mutation had been identified. Seventeen patients harbored mutations in BBS1, 10 in BBS10, and 10 in other genes (BBS2, BBS3, BBS5, BBS7, and BBS12). All the patients underwent ocular examination; 36 patients had computerized full-field electroretinograms (ERGs). RESULTS: Visual acuity was significantly better in BBS1 patients than in patients with other BBS mutations (P=.01), and a larger proportion of BBS1 patients had good (>=20/50) visual acuity (P=.01). The ERG amplitudes were significantly higher in BBS1 patients than in patients with other BBS mutations in response to 0.5-Hz and 30-Hz flashes (P\&lt;.001 for both). All the BBS1 patients harbored at least 1 missense mutation compared with only 45\% of patients with mutations in other BBS genes (P\&lt;.001); the rest harbored only null alleles. However, multivariate analysis demonstrated that visual acuity or ERG amplitude did not depend on the type of mutation present (missense or null) when controlling for BBS gene. Prevalences of bone spicule pigmentation and cataract were comparable in BBS subtypes. CONCLUSIONS: Patients with BBS1 mutations had a milder phenotype than did patients with mutations in other BBS genes. Clinically, this manifested as significantly better visual acuity and larger ERG amplitudes. CLINICAL RELEVANCE: These phenotypic differences can help guide genetic testing and genetic counseling for patients with this syndrome.},
	keywords = {Adolescent, Adult, Bardet-Biedl Syndrome, Child, DNA Mutational Analysis, Electroretinography, Female, Genetic Association Studies, Group II Chaperonins, Humans, Male, Microtubule-Associated Proteins, Middle Aged, Mutation, Retina, Visual Acuity, Young Adult},
	issn = {1538-3601},
	doi = {10.1001/archophthalmol.2012.89},
	author = {Daniels, Anthony B and Sandberg, Michael A and Chen, Jianjun and Weigel-DiFranco, Carol and Fielding Hejtmancic, J and Berson, Eliot L}
}
@article {1363266,
	title = {Complexity of the tear film: importance in homeostasis and dysfunction during disease},
	journal = {Exp Eye Res},
	volume = {117},
	year = {2013},
	month = {2013 Dec},
	pages = {1-3},
	keywords = {Eyelid Diseases, Homeostasis, Humans, Lacrimal Apparatus Diseases, Meibomian Glands, Tears},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2013.10.008},
	author = {Dartt, D A and Willcox, M D P}
}
@article {303951,
	title = {Conjunctival epithelial and goblet cell function in chronic inflammation and ocular allergic inflammation.},
	journal = {Curr Opin Allergy Clin Immunol},
	volume = {14},
	number = {5},
	year = {2014},
	month = {2014 Oct},
	pages = {464-70},
	abstract = {PURPOSE OF REVIEW: Although conjunctival goblet cells are a major cell type in ocular mucosa, their responses during ocular allergy are largely unexplored. This review summarizes the recent findings that provide key insights into the mechanisms by which their function and survival are altered during chronic inflammatory responses, including ocular allergy. RECENT FINDINGS: Conjunctiva represents a major component of the ocular mucosa that harbors specialized lymphoid tissue. Exposure of mucin-secreting goblet cells to allergic and inflammatory mediators released by the local innate and adaptive immune cells modulates proliferation, secretory function, and cell survival. Allergic mediators like histamine, leukotrienes, and prostaglandins directly stimulate goblet cell mucin secretion and consistently increase goblet cell proliferation. Goblet cell mucin secretion is also detectable in a murine model of allergic conjunctivitis. Additionally, primary goblet cell cultures allow evaluation of various inflammatory cytokines with respect to changes in goblet cell mucin secretion, proliferation, and apoptosis. These findings in combination with the preclinical mouse models help understand the goblet cell responses and their modulation during chronic inflammatory diseases, including ocular allergy. SUMMARY: Recent findings related to conjunctival goblet cells provide the basis for novel therapeutic approaches, involving modulation of goblet cell mucin production, to improve treatment of ocular allergies.},
	issn = {1473-6322},
	doi = {10.1097/ACI.0000000000000098},
	author = {Dartt, Darlene A. and Masli, Sharmila}
}
@article {1647892,
	title = {Immunopathology of COVID-19 and its implications in the development of rhino-orbital-cerebral mucormycosis: a major review},
	journal = {Orbit},
	volume = {41},
	number = {6},
	year = {2022},
	month = {2022 Dec},
	pages = {670-679},
	abstract = {PURPOSE: To present a literature review on various immunopathologic dysfunctions following COVID-19 infection and their potential implications in development of rhino-orbital-cerebral mucormycosis (ROCM). METHODS: A literature search was performed via Google Scholar and PubMed with subsequent review of the accompanying references. Analogies were drawn between the immune and physiologic deviations caused by COVID-19 and the tendency of the same to predispose to ROCM. RESULTS: Sixty-two articles were reviewed. SARS-CoV-2 virus infection leads to disruption of epithelial integrity in the respiratory passages, which may be a potential entry point for the ubiquitous Mucorales to become invasive. COVID-19 related GRP78 protein upregulation may aid in spore germination and hyphal invasion by Mucorales. COVID-19 causes interference in macrophage functioning by direct infection, a tendency for hyperglycemia, and creation of neutrophil extracellular traps. This affects innate immunity against Mucorales. Thrombocytopenia and reduction in the number of natural killer (NK) cells and infected dendritic cells is seen in COVID-19. This reduces the host immune response to pathogenic invasion by Mucorales. Cytokines released in COVID-19 cause mitochondrial dysfunction and accumulation of reactive oxygen species, which cause oxidative damage to the leucocytes. Hyperferritinemia also occurs in COVID-19 resulting in suppression of the hematopoietic proliferation of B- and T-lymphocytes. CONCLUSIONS: COVID-19 has a role in the occurrence of ROCM due to its effects at the entry point of the fungus in the respiratory mucosa, effects of the innate immune system, creation of an environment of iron overload, propagation of hyperglycemia, and effects on the adaptive immune system.},
	keywords = {COVID-19, Eye Diseases, Humans, Hyperglycemia, Mucorales, Mucormycosis, Orbital Diseases, SARS-CoV-2},
	issn = {1744-5108},
	doi = {10.1080/01676830.2022.2099428},
	author = {Dave, Tarjani Vivek and Nair, Akshay Gopinathan and Joseph, Joveeta and Freitag, Suzanne K}
}
@article {680401,
	title = {An Atypical Case of Lymphocytic Panhypophysitis in a Pregnant Woman.},
	journal = {J Neuroophthalmol},
	volume = {36},
	number = {3},
	year = {2016},
	month = {2016 Sep},
	pages = {313-6},
	abstract = {We describe a case of lymphocytic panhypophysitis (LPH) in a 30-year-old woman presenting with throbbing headaches and vision changes during her third trimester. LPH is the rarest subclassification of lymphocytic hypophysitis; it is typically found in males and has not previously been associated with pregnancy. Anterior and posterior pituitary deficits together with headaches should raise a high degree of suspicion regarding the possibility of LPH. The atypical magnetic resonance imaging finding of a heterogeneous pituitary mass additionally raised concern about pituitary apoplexy. Tissue from a transsphenoidal biopsy permitted diagnosis of lymphocytic hypophysitis. There was infiltration of the pituitary gland by small B and T lymphocytes. Resolution of the visual symptoms occurred after the biopsy and treatment with intravenous steroids.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000362},
	author = {Davies, Emma C and Jakobiec, Frederick A and Stagner, Anna M and Rizzo, Joseph F}
}
@article {1573129,
	title = {Case Series: Novel Utilization of Rho-Kinase Inhibitor for the Treatment of Corneal Edema},
	journal = {Cornea},
	volume = {40},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {116-120},
	abstract = {PURPOSE: To describe 3 cases of corneal clearance after the use of topical rho-kinase inhibitor, netarsudil, in the setting of endothelial cell dysfunction in comparison to one case without corneal clearance after the use of netarsudil. METHODS: Four patients presenting to a busy academic clinical corneal practice with visual complaints from corneal edema secondary to endothelial cell dysfunction were treated with topical netarsudil one drop daily in the affected eye. RESULTS: Corneal clearance was observed in 1) a case of peripheral corneal edema in the setting of iridocorneal endothelial syndrome after 4 weeks on netarsudil, 2) a case of corneal edema in the setting of early penetrating keratoplasty graft failure after 2-week use of netarsudil, and 3) a case of corneal edema in the setting of chronic penetrating keratoplasty graft failure after 4-week use of netarsudil. Corneal clearance was not observed in a case of corneal edema in the setting of pseudophakic bullous keratopathy from previous complicated intraocular lens exchange surgery with placement of an anterior chamber intraocular lens after the use of netarsudil for 12 weeks. CONCLUSIONS: Addition of topical rho-kinase inhibitor in the form of netarsudil can result in corneal clearance in a variety of certain cases of endothelial cell dysfunction, not previously documented in the literature.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002421},
	author = {Davies, Emma}
}
@article {341651,
	title = {A Rapidly Enlarging Recurrent Eyebrow Pilomatrixoma in a Nonagenarian.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2014},
	month = {2014 Dec 15},
	abstract = {A rapidly growing, large (horizontal diameter of 3.1 cm) eyebrow lesion in a nonagenarian patient was found on pathologic examination to demonstrate an admixture of islands of anucleated, washed out eosinophilic "ghost" cells with surrounding nucleated, small germinal basaloid cells. Further analysis disclosed adipophilin granular positivity in the necrotic zones, negative nuclear staining for androgen receptor and strong nuclear positivity for Ki67 in the basaloid cells (proliferation index of 50\%). These findings are consistent with a highly mitotically active pilomatrixoma. The lesion recurred after initial resection but returned the same histopathologic features as the primary. Several clinical features were notably atypical for pilomatrixoma-specifically, the age of the patient, rapid lesion growth and recurrence, and clinical appearance and large size of the mass. The immunohistochemical findings can help to distinguish this tumor from other skin neoplasms, especially sebaceous carcinoma in an older individual.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000355},
	author = {Davies, Emma C and Jakobiec, Frederick A and Stagner, Anna M and Iwamoto, Mami A}
}
@article {1179141,
	title = {Complications of Scleral-Fixated Intraocular Lenses},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Sep 12},
	pages = {1-6},
	abstract = {INTRODUCTION: Understanding the evolution of complications after scleral-fixated lens placement demonstrates advantageous surgical techniques and suitable candidates. MATERIALS/METHODS: A literature search in PubMed for several terms, including "scleral intraocular lens complication," yielded 17 relevant articles. RESULTS: Reviewing complication trends over time, lens tilt and suture erosion have decreased, cystoid macular edema has increased, and retinal detachment has remained the same after scleral-fixated lens placement. The successful reduction in complications are attributed to several alterations in technique, including positioning sclerotomy sites 180 degrees apart and using scleral flaps or pockets to bury sutures. Possible reduction in retinal risks have been proposed by performing an anterior vitrectomy prior to lens placement in certain settings. DISCUSSION: Complications after scleral-fixated lens placement should assist patient selection. Elderly patients with a history of hypertension should be counseled regarding risk of suprachoroidal hemorrhage, while young patients and postocular trauma patients should be considered for concurrent anterior vitrectomy.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353808},
	author = {Davies, Emma C and Pineda, Roberto}
}
@article {503996,
	title = {Herpes zoster ophthalmicus: declining age at presentation.},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {312-4},
	abstract = {OBJECTIVE: To investigate changes in the age of occurrence of herpes zoster ophthalmicus (HZO) in patients presenting to the Massachusetts Eye and Ear Infirmary (MEEI) from 2007 through 2013. DESIGN: Retrospective chart review. SETTING: Academic tertiary referral centre for ophthalmic conditions. PARTICIPANTS: 913 patients with acute HZO. METHODS: A total of 1283 potential cases were identified by searching the MEEI electronic medical record for patient charts with International Classification of Diseases 9 codes for herpes zoster, shingles and varicella from 2007 through 2013. The cases were reviewed to confirm diagnosis of acute HZO, requiring documentation of a skin rash or pain in the V1 distribution, resulting in inclusion of 913 cases. MAIN OUTCOME MEASURES: Number of HZO cases each year, mean age of HZO cases each year, number of HZO cases with an immunodeficiency state. RESULTS: The number of patients with HZO presenting to MEEI increased from 71 cases in 2007 to 195 cases in 2013. The mean age of patients with acute HZO reduced significantly from 61.2 years in 2007 to 55.8 years in 2013 (p=0.0119). The number of patients with acute HZO in the setting of an immunodeficiency state did not change significantly over the study period. CONCLUSIONS: Ever since the introduction of varicella vaccination in children, there has been debate regarding its effect on zoster epidemiology, particularly regarding the potential to reduce population exposure and limit repeated immunological boosts against varicella zoster virus in adults. Patients presenting to MEEI with HZO were younger on average in 2013 than in 2007. Although a population-based study is necessary to test the hypothesis, our study suggests that varicella vaccination of children remains a possible explanation for the increased number of cases and reduction in mean age of newly diagnosed patients.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-307157},
	author = {Davies, Emma C and Pavan-Langston, Deborah and Chodosh, James}
}
@article {913426,
	title = {OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF MACULAR EDEMA AND HARD EXUDATES AND THEIR ASSOCIATION WITH LIPID SERUM LEVELS IN TYPE 2 DIABETES.},
	journal = {Retina},
	volume = {36},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1622-9},
	abstract = {PURPOSE: To determine whether hyperreflective foci (HF) and macular thickness on spectral domain ocular coherence tomography are associated with lipid levels in patients with Type 2 diabetes. METHODS: Two hundred and thirty-eight participants from four sites had fundus photographs and spectral domain ocular coherence tomography images graded for hard exudates and HF, respectively. Regression models were used to determine the association between serum lipid levels and 1) presence of HF and hard exudates and 2) central subfield macular thickness, central subfield macular volume, and total macular volume. RESULTS: All patients with hard exudates on fundus photographs had corresponding HF on spectral domain ocular coherence tomography, but 57\% of patients with HF on optical coherence tomography did not have hard exudates detected in their fundus photographs. Presence of HF was associated with higher total cholesterol (odds ratio = 1.13, 95\% confidence interval = 1.01-1.27, P = 0.03) and higher low-density lipoprotein levels (odds ratio = 1.17, 95\% confidence interval = 1.02-1.35, P = 0.02) in models adjusting for other risk factors. The total macular volume was also associated with higher total cholesterol (P = 0.009) and triglyceride (P = 0.02) levels after adjusting for other risk factors. CONCLUSION: Higher total and low-density lipoprotein cholesterol were associated with presence of HF on spectral domain ocular coherence tomography. Total macular volume was associated with higher total cholesterol and triglyceride levels.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001022},
	author = {Davoudi, Samaneh and Papavasileiou, Evangelia and Roohipoor, Ramak and Cho, Heeyoon and Kudrimoti, Shreyas and Hancock, Heather and Hoadley, Suzanne and Andreoli, Christopher and Husain, Deeba and James, Maurice and Penman, Alan and Chen, Ching J and Sobrin, Lucia}
}
@article {931041,
	title = {Phage Immunoprecipitation Sequencing of Autoantigens in Autoimmune Retinopathy.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Oct 11},
	pages = {1-8},
	abstract = {PURPOSE: To identify autoantigens in autoimmune retinopathy patients by phage immunoprecipitation sequencing (PhIP-Seq), a new technique for autoantigen discovery. METHODS: PhIP-Seq was used to sequence putative autoantibodies in plasma from 11 patients with autoimmune retinopathy and eight controls. We compared the autoantibodies{\textquoteright} molecular weights with those of proteins detected by Western blot. RESULTS: Several autoantigens were found in cases and not detected in the controls. Autoantigens RTN3, PRPF6, TRPC6, and B3GNT8, four proteins expressed in the retina, were detected in plasma as autoantibodies from one patient each and no controls. Only one patient had an autoantibody, B3GNT8 (43.4 kDa), within a similar weight range as that detected by antiretinal antibody Western blot (42 kDa). Autoantibody POLR3A, which has a well-characterized role in scleroderma, was detected in two cases and no controls. CONCLUSION: PhIP-Seq detected autoantigens that are expressed in the retina as well as scleroderma-related autoantigens in autoimmune retinopathy patients.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2016.1232738},
	author = {Davoudi, Samaneh and Ahmadi, Tina and Papavasilieou, Evangelia and Leskov, Ilya and Sobrin, Lucia}
}
@article {1078731,
	title = {Outcomes in Autoimmune Retinopathy Patients Treated With Rituximab},
	journal = {Am J Ophthalmol},
	volume = {180},
	year = {2017},
	month = {2017 Aug},
	pages = {124-132},
	abstract = {PURPOSE: To evaluate clinical and ancillary testing, including adaptive optics, outcomes in autoimmune retinopathy (AIR) patients treated with rituximab. DESIGN: Retrospective, interventional case series. METHODS: patients: Sixteen AIR patients treated with rituximab. OBSERVATION PROCEDURES: All patients were treated with a loading and maintenance dose schedule of intravenous rituximab. Visual acuity (VA), electroretinography (ERG), and spectral-domain optical coherence tomography (SDOCT) and visual field (VF) results were recorded. A subset of patients was also imaged using adaptive optics scanning laser ophthalmoscopy (AO-SLO). MAIN OUTCOME MEASURES: Rates of VA change before vs after rituximab initiation were compared with mixed-model linear regression. RESULTS: The rate of visual decline was significantly less after rituximab initiation compared with the rate of visual decline prior to rituximab initiation (P\&nbsp;= .005). Seventy-seven percent of eyes had stable or improved VA 6\&nbsp;months after rituximab initiation. Amplitudes and implicit times on ERG, mean deviation on VF, central subfield mean thickness, and total macular volume did not decrease to a significant degree over the rituximab treatment period. Six eyes had serial AO-SLO imaging. Cone densities did not change significantly over the treatment period. CONCLUSION: VA was stable or improved in a majority of AIR patients while they were being treated with rituximab. OCT and ERG parameters, as well as AO-SLO cone densities, were stable during treatment. Studies with additional patients and longer follow-up periods are needed to further explore the utility of rituximab in the management of AIR.},
	keywords = {Adult, Aged, Autoantibodies, Autoimmune Diseases, Electroretinography, Female, Humans, Immunologic Factors, Intravitreal Injections, Male, Middle Aged, Ophthalmoscopy, Outcome Assessment (Health Care), Retina, Retinal Diseases, Retrospective Studies, Rituximab, Tomography, Optical Coherence, Visual Acuity, Visual Fields},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.04.019},
	author = {Davoudi, Samaneh and Ebrahimiadib, Nazanin and Yasa, Cagla and Sevgi, Damla D and Roohipoor, Ramak and Papavasilieou, Evangelia and Comander, Jason and Sobrin, Lucia}
}
@article {1593870,
	title = {A Review of Ophthalmic Telemedicine for Emergency Department Settings},
	journal = {Semin Ophthalmol},
	volume = {37},
	number = {1},
	year = {2022},
	month = {2022 Jan 02},
	pages = {83-90},
	abstract = {BACKGROUND: Patients presenting to emergency departments for ophthalmic emergencies benefit from prompt evaluation. However, Few emergency departments (EDs) have ophthalmologists on call, and eye care provided in EDs without ophthalmic services can be inaccurate. METHODS: We review the current state of ophthalmic telemedical care in EDs and highlight important considerations when implementing telemedicine in this setting. RESULTS: Telemedicine allows ophthalmologists to work with on-site emergency care providers to interview and examine patients remotely in EDs, enabling proper assessment of patient history, visual acuity, pupils, intraocular pressure, as well as the anterior and posterior segment. To date, patients{\textquoteright} perceptions of this new model of care have been largely positive. DISCUSSION: The use of telemedical consultations for remote evaluation of patients with ophthalmic complaints stands to improve the quality of care provided to patients and extend the reach of remote ophthalmologists. The onset of the COVID-19 pandemic and the risk of in-person\&nbsp;care further highlights the potential for telemedicine to augment existing models of emergency care.},
	keywords = {COVID-19, Emergency Service, Hospital, Humans, Pandemics, SARS-CoV-2, Telemedicine},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1922712},
	author = {De Arrigunaga, Sofia and Aziz, Kanza and Lorch, Alice C and Friedman, David S and Armstrong, Grayson W}
}
@article {1661818,
	title = {Prospective, Randomized, Multicenter, Double-Masked, Clinical Trial of Corneal Cross-Linking for Boston Keratoprosthesis Carrier Tissue},
	journal = {Am J Ophthalmol},
	volume = {249},
	year = {2023},
	month = {2023 May},
	pages = {39-48},
	abstract = {PURPOSE: To assess whether cross-linking the carrier donor cornea of the Boston Keratoprosthesis (BKPro) improves retention of the device in participants at high risk for keratolysis. DESIGN: Prospective, double-masked, randomized clinical trial. METHODS: In this multicenter study, 68 adult participants who were scheduled for BKPro implantation were enrolled. Masked participants were randomized to receive either a cross-linked (CXL) or non-cross-linked (non-CXL) donor corneal carrier. The Kaplan-Meier event-free survival was determined by the product-limit method and compared by the log-rank test to examine whether survival curves were different between the CXL and non-CXL groups. The primary outcome of the study was time from surgery to BKPro removal. The secondary endpoint was 12-month retention rate. RESULTS: A total of 68 participants were enrolled and randomized 1:1 to each group. The average age at the time of surgery was 62 (range\&nbsp;=\&nbsp;24-89) years, and 42 participants (62\%) were male. The overall BKPro retention rate was 70\% during a mean follow-up time of 93 (range\&nbsp;=\&nbsp;6-201) weeks. Twenty BKPros were removed, 10 in the CXL group and 10 in the non-CXL group, with 18 requiring removal because of sterile keratolysis. There was no difference in the time to removal between the groups during the study (P\&nbsp;=\&nbsp;.910). At 12 months, there was no significant difference in the retention rate in the CXL group (94\%) vs the non-CXL group (82\%, P\&nbsp;=\&nbsp;.150). CONCLUSIONS: In this prospective study, cross-linking of the carrier cornea prior to BKPro implantation did not reduce the incidence of sterile keratolysis or increase device retention among participants at high risk for retention failure.},
	keywords = {Adult, Aged, Aged, 80 and over, Cornea, Corneal Cross-Linking, Corneal Diseases, Cross-Linking Reagents, Female, Humans, Keratoconus, Male, Middle Aged, Photosensitizing Agents, Prospective Studies, Prostheses and Implants, Riboflavin, Ultraviolet Rays, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.12.017},
	author = {De Arrigunaga, Sofia and Akpek, Esen K and Aldave, Anthony J and Mian, Shahzad I and Zurakowski, David and Ciolino, Joseph B and Boston Keratoprosthesis Cross-linking Study Group}
}
@article {1748446,
	title = {The Development of Retinal Function and Refractive Error in Children With Retinopathy of Prematurity},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {11},
	year = {2023},
	month = {2023 Aug 01},
	pages = {35},
	abstract = {PURPOSE: The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at 10\&nbsp;degrees but not 30\&nbsp;degrees eccentricity. In addition, to evaluate the thresholds at each site for an association with visual acuity (VA) and spherical equivalent (SE). METHODS: We estimated rod-mediated dark-adapted thresholds (DATs) for the detection of 2\&nbsp;degree diameter, 50\&nbsp;ms, blue (λ \&lt; 510\&nbsp;nm) flashes at 10\&nbsp;degrees and 30\&nbsp;degrees eccentric in former preterm subjects (n = 111), stratified by ROP severity: None (n = 32), Mild (n = 66), and Severe (n = 13). We also tested Term-born (n = 28) controls. To determine the age at half-maximal sensitivity (Agehalf) for each group and eccentricity, we fit DATs to logistic growth curves. We obtained VA and SE for Preterm subjects and evaluated the course of threshold development at 10\&nbsp;degrees and 30\&nbsp;degrees for significant association with VA and SE predicted at age 10 years. RESULTS: DAT development at 10\&nbsp;degrees was significantly delayed in ROP (Mild and Severe); ROP did not significantly alter DAT development at 30\&nbsp;degrees. At age 10\&nbsp;years, among Preterm subjects, both VA and SE were significantly associated with group (None,Mild, and Severe). SE was predicted by the course of DAT development at 30\&nbsp;degrees. VA was not associated with the course of DAT development at 10\&nbsp;degrees. CONCLUSIONS: At 10\&nbsp;degrees, ROP-whether mild or severe-is associated with significant delays in DAT development, evidence that the late-maturing central retina is vulnerable to ROP. The association of 30\&nbsp;degree threshold and myopia are evidence that more peripheral retina is important to refractive development.},
	keywords = {Child, Humans, Infant, Newborn, Refraction, Ocular, Refractive Errors, Retina, Retinopathy of Prematurity, Visual Acuity},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.11.35},
	author = {De Bruyn, Hanna and Hansen, Ronald M and Akula, James D and Fulton, Anne B}
}
@article {1364599,
	title = {Dynamic imaging of paralytic eyelid disorders},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {167-74},
	abstract = {PURPOSE: Eyelid dysmotility may result from trauma, tumors, inflammation, infection, and a variety of other conditions. In these cases, a mechanical effect is disrupting a normal neuromuscular apparatus. Dysmotility can also be caused by paralytic eyelid disorders; included in this broad category are neurologic and myogenic disorders of eyelid opening and/or closure. Secondary effects include spastic eyelid closure and synkinesis syndromes. These conditions, by definition, are disorders of movement, and can only be studied adequately using dynamic imaging techniques. METHODS: A comprehensive literature search was performed on PubMed. Ninety abstracts were reviewed. RESULTS: Dynamic eyelid imaging has evolved dramatically over the past two decades, at least partially due to the rise of inexpensive digital technology. Magnetic search coil imaging, high- and low-speed videography, electromyography, and high-resolution microscopy coil magnetic resonance imaging each has its advantages and disadvantages, an understanding of which will guide appropriate selection of technology in any given clinical situation. CONCLUSIONS: Dynamic eyelid imaging is useful to study dysmotility. The optimal technique depends upon the clinical setting and the physiologic or pathologic topic of interest. To our knowledge, a report of this type has not been previously summarized.},
	keywords = {Diagnostic Imaging, Diagnostic Techniques, Ophthalmological, Eyelid Diseases, Eyelids, Facial Paralysis, Humans, Ophthalmoplegia},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.708804},
	author = {De Castro, Dawn K and Hadlock, Tessa and Fay, Aaron}
}
@article {1363267,
	title = {A modified lacrimal sac implant for high-risk dacryocystorhinostomy},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {5},
	year = {2013},
	month = {2013 Sep-Oct},
	pages = {367-72},
	abstract = {PURPOSE: The reported 5\% of patients with nasolacrimal duct obstruction who fail dacryocystorhinostomy likely include patients with severe mucosal disease or anatomical anomalies. The technique described herein avoids mucosal anastomosis and minimizes mucosal manipulation by inserting a permanent silicone conduit from the lacrimal sac into the nasal cavity.

METHODS: This retrospective review of 9 surgical cases was performed with institutional review board approval. Six patients underwent 9 surgeries (3 sequentially bilateral) for dacryocystitis. Two patients had Wegener granulomatosis, 1 had pemphigoid, 1 sarcoidosis, 1 Rosai-Dorfman disease, and 1 congenital choanal atresia with chronic neonatal dacryocystitis. In each case, a modified Rains sinus stent was inserted through an external lacrimal sac incision with the draining end positioned in the nasal cavity. Two patients underwent concurrent canalicular intubation with Guibor silicone stents to prevent internal punctum obstruction by the lacrimal sac implant. Recurrence of symptoms, patient comfort, and modified Rains stent stability and patency were evaluated.

RESULTS: Mean follow up was 30 months (range 7-59 months). The modified Rains stent remained stable and patent in 7 of 9 cases, and symptoms resolved in 8 of 9 cases. In 1 patient with sarcoidosis, the modified Rains stent became repeatedly obstructed with nasal secretions and ultimately dislodged after intranasal manipulation by a physician unfamiliar with the surgery. In no other case did the patient experience recurrent infection, and in those cases, epiphora resolved entirely. In the patient with pemphigoid, one of the modified Rains stents extruded 6 months postoperatively, but his symptoms remained controlled. No adverse reaction to the implant material was seen.

CONCLUSIONS: A Rains silicone frontal sinus stent can be modified for implantation into the lacrimal sac and can safely and effectively drain the lacrimal sac into the nose in patients with severe mucosal disease or anatomical anomalies. Additional study and a stent specifically designed for this application will likely improve outcomes.},
	keywords = {Adult, Dacryocystorhinostomy, Female, Follow-Up Studies, Humans, Intubation, Lacrimal Duct Obstruction, Male, Nasolacrimal Duct, Radiography, Retrospective Studies, Stents},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31829a72d4},
	author = {De Castro, Dawn K and Santiago, Yvette Marie B and Cunningham, Michael and Gray, Stacey T and Metson, Ralph and Fay, Aaron}
}
@article {1363268,
	title = {Self-irrigating piezoelectric device in orbital surgery},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {2},
	year = {2013},
	month = {2013 Mar-Apr},
	pages = {118-22},
	abstract = {PURPOSE: Orbital osteotomy risks injury to the eyeball and orbit soft tissues. Used extensively in oral and maxillofacial surgery, piezoelectric technology offers a greater margin of safety than traditional bone cutting instruments. The authors describe the novel use of this system in a variety of orbital surgeries. METHODS: This interventional case series was performed in accordance with institutional review board regulations. The medical records of all patients who had undergone orbital surgery using the piezoelectric blade at 3 institutions were reviewed. Indication for surgery, gender, age, duration of follow up, intraoperative complications, surgical result, and postoperative course was recorded. RESULTS: Sixteen patients underwent surgery on 18 orbits using the piezoelectric system between August 2011 and June 2012. Surgeries performed included orbital decompression (8), lateral orbitotomy (5), cranio-orbitotomy (4), and external dacryocystorhinostomy (1). Eight were female and 8 were male patients. Mean age was 55 years old (standard deviation 15 years). Mean follow up was 82 days. The osteotomy created by the blade was narrow and smooth in every case. The surgeons uniformly appreciated the precision and safety of the instrument compared with traditional electric saw blades. There were no soft tissue lacerations or intraoperative complications and reconstructions were uniformly uneventful. Postoperative healing was rapid with no unexpected inflammation, and no palpable bony defects were appreciated in the reconstructed cases. CONCLUSIONS: Because it does not cut soft tissue and cuts a narrow trough, the self-irrigating piezoelectric saw blade appears safer and more precise than traditional electric saw blades in and around the orbit.},
	keywords = {Adult, Aged, Aged, 80 and over, Eye Diseases, Female, Follow-Up Studies, Humans, Intraoperative Complications, Male, Middle Aged, Orbit, Osteotomy, Piezosurgery, Postoperative Complications, Retrospective Studies, Therapeutic Irrigation, Treatment Outcome},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31827f59d4},
	author = {De Castro, Dawn K and Fay, Aaron and Wladis, Edward J and Nguyen, John and Osaki, Tammy and Metson, Ralph and Curry, William}
}
@article {1782271,
	title = {Persistent Inflammation Associated With HLA-B27 After Pars Plana Vitrectomy With Scleral Buckle Placement},
	journal = {J Vitreoretin Dis},
	volume = {7},
	number = {6},
	year = {2023},
	month = {2023 Nov-Dec},
	pages = {557-561},
	abstract = {Purpose: To report 2 cases of persistent inflammation associated with human leukocyte antigen-B27 (HLA-B27) after pars plana vitrectomy (PPV) with scleral buckling. Methods: Two cases were analyzed. Results: A 47-year-old man had pars plana vitrectomy (PPV), scleral buckle (SB) placement, and endolaser for a macula-on rhegmatogenous retinal detachment (RRD). A 61-year-old man also had uneventful PPV, SB placement, and endolaser for a macula-off RRD. Postoperatively, both patients reported eye pain and had persistent intraocular inflammation. Both were found to be HLA-B27 positive despite having no previous signs or symptoms that would warrant HLA-B27 testing. Conclusions: Discovering the source of prolonged postoperative inflammation is critical in initiating the correct treatment and removing suspicion of infection. Although intraocular inflammation associated with HLA-B27 does not often present initially after surgery, HLA-B27 testing should be considered in cases of persistent, unexpected postoperative inflammation.},
	issn = {2474-1272},
	doi = {10.1177/24741264231176143},
	author = {Dean, Jordan and McTavish, Sloane and Feng, Yilin and Hoyek, Sandra and Patel, Nimesh A}
}
@article {1213806,
	title = {Genetics of age-related macular degeneration (AMD)},
	journal = {Hum Mol Genet},
	volume = {26},
	number = {R2},
	year = {2017},
	month = {2017 Oct 01},
	pages = {R246},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddx343},
	author = {Deangelis, Margaret M and Owen, Leah A and Morrison, Margaux A and Morgan, Denise J and Li, Mingyao and Shakoor, Akbar and Vitale, Albert and Iyengar, Sudha and Stambolian, Dwight and Kim, Ivana K and Farrer, Lindsay A}
}
@article {369001,
	title = {Pharmacogenomics of response to anti-VEGF therapy in exudative age-related macular degeneration.},
	journal = {Retina},
	volume = {35},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {381-91},
	abstract = {PURPOSE: To determine whether there is an association between response to intravitreal anti-vascular endothelial growth factor agents and genotype in patients with neovascular age-related macular degeneration. METHODS: Analysis of the current literature evaluating pharmacogenetics of treatment response in patients with neovascular age-related macular degeneration. RESULTS: Studies have demonstrated associations between various genotypes and response to intravitreal anti-vascular endothelial growth factor agents. Lower-risk genotypes of the CFH, ARMS2, HTRA1, and VEGF-A genes may be associated with improved visual outcomes. Additionally, frequency of injections may be associated with certain genotypes. CONCLUSION: Genetic background may influence an individual{\textquoteright}s response to treatment of neovascular age-related macular degeneration. Further studies to investigate biologic pathways of neovascular age-related macular degeneration and gene products that are directly involved might lead to better understanding of contribution of various genes to treatment response.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000466},
	author = {Dedania, Vaidehi S and Grob, Seanna and Zhang, Kang and Bakri, Sophie J}
}
@article {1559530,
	title = {Enabling hope},
	journal = {Lancet Oncol},
	volume = {21},
	number = {12},
	year = {2020},
	month = {2020 12},
	pages = {e549},
	keywords = {Emotions, Hope, Humans},
	issn = {1474-5488},
	doi = {10.1016/S1470-2045(20)30616-1},
	author = {Dee, Edward Christopher and Mitchell, William Greig and D{\textquoteright}Amico, Anthony V}
}
@article {1635623,
	title = {Use and Perceptions of Advanced Driver Assistance Systems by Older Drivers With and Without Age-Related Macular Degeneration},
	journal = {Transl Vis Sci Technol},
	volume = {11},
	number = {3},
	year = {2022},
	month = {2022 Mar 02},
	pages = {22},
	abstract = {Purpose: Advanced driver assistance systems (ADAS) have been reported to improve the safety of elderly and normally sighted drivers. The purpose of this study was to assess exposure to, perceived safety of, comfort level with, and interest in using ADAS among drivers with age-related macular degeneration (AMD). Methods: Current drivers aged 60+ years were recruited at four US sites to complete a survey about ADAS and driving habits. Frequency of use and/or perceptions of eight ADAS were investigated. An avoidance score was generated using questions about difficult driving situations. Results: The survey was completed by 166 participants (80 with AMD vs. 86 without). Participants with AMD had worse self-rated vision than those without (34\% vs. 2\% poor or fair rating), and drove fewer weekly miles (median [interquartile range [IQR] 30 [15 to 75] vs. 60 [30 to 121] miles, P = 0.002). Participants with AMD reported more avoidance of difficult driving situations (P \&lt; 0.001). There was no difference in the number of ADAS used by AMD status (median [IQR for AMD = 2.5 [1 to 5] vs. 3 [2 to 4] without, P = 0.87). Greater reported number of ADAS used was associated with less avoidance of difficult situations (P = 0.02). The majority perceived improved safety with most ADAS. Conclusions: Many drivers with AMD utilize common ADAS, which subjectively improve their road safety and may help to reduce self-imposed restrictions for difficult situations and mileage. Translational Relevance: Drivers with AMD are adopting readily available ADAS, for which they reported potential benefits, such as safety and less restrictive driving.},
	issn = {2164-2591},
	doi = {10.1167/tvst.11.3.22},
	author = {Deffler, Rebecca A and Xu, Jing and Bittner, Ava K and Bowers, Alex R and Hassan, Shirin E and Ross, Nicole and Cooley, San-San L and Doubt, Aprile and Davidorf, Frederick H and Dougherty, Bradley E and RADARS Study Group}
}
@article {1125281,
	title = {Genome-wide screen for genes involved in eDNA release during biofilm formation by Staphylococcus aureus},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	number = {29},
	year = {2017},
	month = {2017 Jul 18},
	pages = {E5969-E5978},
	abstract = {Staphylococcus aureus is a leading cause of both nosocomial and community-acquired infection. Biofilm formation at the site of infection reduces antimicrobial susceptibility and can lead to chronic infection. During biofilm formation, a subset of cells liberate cytoplasmic proteins and DNA, which are repurposed to form the extracellular matrix that binds the remaining cells together in large clusters. Using a strain that forms robust biofilms in vitro during growth under glucose supplementation, we carried out a genome-wide screen for genes involved in the release of extracellular DNA (eDNA). A high-density transposon insertion library was grown under biofilm-inducing conditions, and the relative frequency of insertions was compared between genomic DNA (gDNA) collected from cells in the biofilm and eDNA from the matrix. Transposon insertions into genes encoding functions necessary for eDNA release were identified by reduced representation in the eDNA. On direct testing, mutants of some of these genes exhibited markedly reduced levels of eDNA and a concomitant reduction in cell clustering. Among the genes with robust mutant phenotypes were gdpP, which encodes a phosphodiesterase that degrades the second messenger cyclic-di-AMP, and xdrA, the gene for a transcription factor that, as revealed by RNA-sequencing analysis, influences the expression of multiple genes, including many involved in cell wall homeostasis. Finally, we report that growth in biofilm-inducing medium lowers cyclic-di-AMP levels and does so in a manner that depends on the gdpP phosphodiesterase gene.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1704544114},
	author = {DeFrancesco, Alicia S and Masloboeva, Nadezda and Syed, Adnan K and DeLoughery, Aaron and Niels Bradshaw and Li, Gene-Wei and Gilmore, Michael S and Walker, Suzanne and Losick, Richard}
}
@article {1445321,
	title = {A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts},
	journal = {J Virol},
	volume = {93},
	number = {18},
	year = {2019},
	month = {2019 Sep 15},
	abstract = {Genomics analysis of a historically intriguing and predicted emergent human adenovirus (HAdV) pathogen, which caused pneumonia and death, provides insight into a novel molecular evolution pathway involving "ping-pong" zoonosis and anthroponosis. The genome of this promiscuous pathogen is embedded with evidence of unprecedented multiple, multidirectional, stable, and reciprocal cross-species infections of hosts from three species (human, chimpanzee, and bonobo). This recombinant genome, typed as HAdV-B76, is identical to two recently reported simian AdV (SAdV) genomes isolated from chimpanzees and bonobos. Additionally, the presence of a critical adenoviral replication element found in HAdV genomes, in addition to genes that are highly similar to counterparts in other HAdVs, reinforces its potential as a human pathogen. Reservoirs in nonhuman hosts may explain periods of apparent absence and then reemergence of human adenoviral pathogens, as well as present pathways for the genesis of those thought to be newly emergent. The nature of the HAdV-D76 genome has implications for the use of SAdVs as gene delivery vectors in human gene therapy and vaccines, selected to avoid preexisting and potentially fatal host immune responses to HAdV. An emergent adenoviral human pathogen, HAdV-B76, associated with a fatality in 1965, shows a remarkable degree of genome identity with two recently isolated simian adenoviruses that contain cross-species genome recombination events from three hosts: human, chimpanzee, and bonobo. Zoonosis (nonhuman-to-human transmission) and anthroponosis (human to nonhuman transmission) may play significant roles in the emergence of human adenoviral pathogens.},
	issn = {1098-5514},
	doi = {10.1128/JVI.00564-19},
	author = {Dehghan, Shoaleh and Seto, Jason and Liu, Elizabeth B and Ismail, Ashrafali M and Madupu, Ramana and Heim, Albert and Jones, Morris S and Dyer, David W and Chodosh, James and Seto, Donald}
}
@article {1635657,
	title = {Sustained Reductions in Online Search Interest for Communicable Eye and Other Conditions During the COVID-19 Pandemic: Infodemiology Study},
	journal = {JMIR Infodemiology},
	volume = {2},
	number = {1},
	year = {2022},
	month = {2022 Jan-Jun},
	pages = {e31732},
	abstract = {Background: In a prior study at the start of the pandemic, we reported reduced numbers of Google searches for the term "conjunctivitis" in the United States in March and April 2020 compared with prior years. As one explanation, we conjectured that reduced information-seeking may have resulted from social distancing reducing contagious conjunctivitis cases. Here, after 1 year of continued implementation of social distancing, we asked if there have been persistent reductions in searches for "conjunctivitis," and similarly for other communicable disease terms, compared to control terms. Objective: The aim of this study was to determine if reduction in searches in the United States for terms related to conjunctivitis and other common communicable diseases occurred in the spring-winter season of the COVID-19 pandemic, and to compare this outcome to searches for terms representing noncommunicable conditions, COVID-19, and to seasonality. Methods: Weekly relative search frequency volume data from Google Trends for 68 search terms in English for the United States were obtained for the weeks of March 2011 through February 2021. Terms were classified a priori as 16 terms related to COVID-19, 29 terms representing communicable conditions, and 23 terms representing control noncommunicable conditions. To reduce bias, all analyses were performed while masked to term names, classifications, and locations. To test for the significance of changes during the pandemic, we detrended and compared postpandemic values to those expected based on prepandemic trends, per season, computing one- and two-sided P values. We then compared these P values between term groups using Wilcoxon rank-sum and Fisher exact tests to assess if non-COVID-19 terms representing communicable diseases were more likely to show significant reductions in searches in 2020-2021 than terms not representing such diseases. We also assessed any relationship between a term{\textquoteright}s seasonality and a reduced search trend for the term in 2020-2021 seasons. P values were subjected to false discovery rate correction prior to reporting. Data were then unmasked. Results: Terms representing conjunctivitis and other communicable conditions showed a sustained reduced search trend in the first 4 seasons of the 2020-2021 COVID-19 pandemic compared to prior years. In comparison, the search for noncommunicable condition terms was significantly less reduced (Wilcoxon and Fisher exact tests, P\&lt;.001; summer, autumn, winter). A significant correlation was also found between reduced search for a term in 2020-2021 and seasonality of that term (Theil-Sen, P\&lt;.001; summer, autumn, winter). Searches for COVID-19-related conditions were significantly elevated compared to those in prior years, and searches for influenza-related terms were significantly lower than those for prior years in winter 2020-2021 (P\&lt;.001). Conclusions: We demonstrate the low-cost and unbiased use of online search data to study how a wide range of conditions may be affected by large-scale interventions or events such as social distancing during the COVID-19 pandemic. Our findings support emerging clinical evidence implicating social distancing and the COVID-19 pandemic in the reduction of communicable disease and on ocular conditions.},
	issn = {2564-1891},
	doi = {10.2196/31732},
	author = {Deiner, Michael S and Seitzman, Gerami D and Kaur, Gurbani and McLeod, Stephen D and Chodosh, James and Lietman, Thomas M and Porco, Travis C}
}
@article {1517204,
	title = {Ocular Signs of COVID-19 Suggested by Internet Search Term Patterns Worldwide},
	journal = {Ophthalmology},
	volume = {128},
	number = {1},
	year = {2021},
	month = {2021 01},
	pages = {167-169},
	keywords = {COVID-19, Eye Diseases, Global Health, Humans, Internet, Morbidity, SARS-CoV-2, Search Engine},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.06.026},
	author = {Deiner, Michael S and Seitzman, Gerami D and McLeod, Stephen D and Chodosh, James and Hwang, Daniel H and Lietman, Thomas M and Porco, Travis C}
}
@article {1435398,
	title = {Google Searches and Detection of Conjunctivitis Epidemics Worldwide},
	journal = {Ophthalmology},
	volume = {126},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {1219-1229},
	abstract = {PURPOSE: Epidemic and seasonal infectious conjunctivitis outbreaks can impact education, workforce, and economy adversely. Yet conjunctivitis typically is not a reportable disease, potentially delaying mitigating intervention. Our study objective was to determine if conjunctivitis epidemics could be identified using Google Trends search data. DESIGN: Search data for conjunctivitis-related and control search terms from 5 years and countries worldwide were obtained. Country and term were masked. Temporal scan statistics were applied to identify candidate epidemics. Candidates then were assessed for geotemporal concordance with an a priori defined collection of known reported conjunctivitis outbreaks, as a measure of sensitivity. PARTICIPANTS: Populations by country that searched Google{\textquoteright}s search engine using our study terms. MAIN OUTCOME MEASURES: Percent of known conjunctivitis outbreaks also found in the same country and period by our candidate epidemics, identified from conjunctivitis-related searches. RESULTS: We identified 135 candidate conjunctivitis epidemic periods from 77 countries. Compared with our a priori defined collection of known reported outbreaks, candidate conjunctivitis epidemics identified 18 of 26 (69\% sensitivity) of the reported country-wide or island nationwide outbreaks, or both; 9 of 20 (45\% sensitivity) of the reported region or district-wide outbreaks, or both; but far fewer nosocomial and reported smaller outbreaks. Similar overall and individual sensitivity, as well as specificity, were found on a country-level basis. We also found that 83\% of our candidate epidemics had start dates before (of those, 20\% were more than 12 weeks before) their concurrent reported outbreak{\textquoteright}s report issuance date. Permutation tests provided evidence that on average, conjunctivitis candidate epidemics occurred geotemporally closer to outbreak reports than chance alone suggests (P \&lt; 0.001) unlike control term candidates (P\&nbsp;= 0.40). CONCLUSIONS: Conjunctivitis outbreaks can be detected using temporal scan analysis of Google search data alone, with more than 80\% detected before an outbreak report{\textquoteright}s issuance date, some as early as the reported outbreak{\textquoteright}s start date. Future approaches using data from smaller regions, social media, and more search terms may improve sensitivity further and cross-validate detected candidates, allowing identification of candidate conjunctivitis epidemics from Internet search data potentially to complementarily benefit traditional reporting and detection systems to improve epidemic awareness.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.04.008},
	author = {Deiner, Michael S and McLeod, Stephen D and Wong, Jessica and Chodosh, James and Lietman, Thomas M and Porco, Travis C}
}
@article {1642027,
	title = {A Google Trends Approach to Identify Distinct Diurnal and Day-of-Week Web-Based Search Patterns Related to Conjunctivitis and Other Common Eye Conditions: Infodemiology Study},
	journal = {J Med Internet Res},
	volume = {24},
	number = {7},
	year = {2022},
	month = {2022 Jul 05},
	pages = {e27310},
	abstract = {BACKGROUND: Studies suggest diurnal patterns of occurrence of some eye conditions. Leveraging new information sources such as web-based search data to learn more about such patterns could improve the understanding of patients{\textquoteright} eye-related conditions and well-being, better inform timing of clinical and remote eye care, and improve precision when targeting web-based public health campaigns toward underserved populations. OBJECTIVE: To investigate our hypothesis that the public is likely to consistently search about different ophthalmologic conditions at different hours of the day or days of week, we conducted an observational study using search data for terms related to ophthalmologic conditions such as conjunctivitis. We assessed whether search volumes reflected diurnal or day-of-week patterns and if those patterns were distinct from each other. METHODS: We designed a study to analyze and compare hourly search data for eye-related and control search terms, using time series regression models with trend and periodicity terms to remove outliers and then estimate diurnal effects. We planned a Google Trends setting, extracting data from 10 US states for the entire year of 2018. The exposure was internet search, and the participants were populations who searched through Google{\textquoteright}s search engine using our chosen study terms. Our main outcome measures included cyclical hourly and day-of-week web-based search patterns. For statistical analyses, we considered P\&lt;.001 to be statistically significant. RESULTS: Distinct diurnal (P\&lt;.001 for all search terms) and day-of-week search patterns for eye-related terms were observed but with differing peak time periods and cyclic strengths. Some diurnal patterns represented those reported from prior clinical studies. Of the eye-related terms, "pink eye" showed the largest diurnal amplitude-to-mean ratios. Stronger signal was restricted to and peaked in mornings, and amplitude was higher on weekdays. By contrast, "dry eyes" had a higher amplitude diurnal pattern on weekends, with stronger signal occurring over a broader evening-to-morning period and peaking in early morning. CONCLUSIONS: The frequency of web-based searches for various eye conditions can show cyclic patterns according to time of the day or week. Further studies to understand the reasons for these variations may help supplement the current clinical understanding of ophthalmologic symptom presentation and improve the timeliness of patient messaging and care interventions.},
	keywords = {Conjunctivitis, Eye Diseases, Humans, Infodemiology, Internet, Search Engine},
	issn = {1438-8871},
	doi = {10.2196/27310},
	author = {Deiner, Michael S and Kaur, Gurbani and McLeod, Stephen D and Schallhorn, Julie M and Chodosh, James and Hwang, Daniel H and Lietman, Thomas M and Porco, Travis C}
}
@article {1302176,
	title = {Clinical Age-Specific Seasonal Conjunctivitis Patterns and Their Online Detection in Twitter, Blog, Forum, and Comment Social Media Posts},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {2},
	year = {2018},
	month = {2018 Feb 01},
	pages = {910-920},
	abstract = {Purpose: We sought to determine whether big data from social media might reveal seasonal trends of conjunctivitis, most forms of which are nonreportable. Methods: Social media posts (from Twitter, and from online forums and blogs) were classified by age and by conjunctivitis type (allergic or infectious) using Boolean and machine learning methods. Based on spline smoothing, we estimated the circular mean occurrence time (a measure of central tendency for occurrence) and the circular variance (a measure of uniformity of occurrence throughout the year, providing an index of seasonality). Clinical records from a large tertiary care provider were analyzed in a similar way for comparison. Results: Social media posts machine-coded as being related to infectious conjunctivitis showed similar times of occurrence and degree of seasonality to clinical infectious cases, and likewise for machine-coded allergic conjunctivitis posts compared to clinical allergic cases. Allergic conjunctivitis showed a distinctively different seasonal pattern than infectious conjunctivitis, with a mean occurrence time later in the spring. Infectious conjunctivitis for children showed markedly greater seasonality than for adults, though the occurrence times were similar; no such difference for allergic conjunctivitis was seen. Conclusions: Social media posts broadly track the seasonal occurrence of allergic and infectious conjunctivitis, and may be a useful supplement for epidemiologic monitoring.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-22818},
	author = {Deiner, Michael S and McLeod, Stephen D and Chodosh, James and Oldenburg, Catherine E and Fathy, Cherie A and Lietman, Thomas M and Porco, Travis C}
}
@article {836801,
	title = {Surveillance Tools Emerging From Search Engines and Social Media Data for Determining Eye Disease Patterns.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {9},
	year = {2016},
	month = {2016 Sep 1},
	pages = {1024-30},
	abstract = {IMPORTANCE: Internet-based search engine and social media data may provide a novel complementary source for better understanding the epidemiologic factors of infectious eye diseases, which could better inform eye health care and disease prevention. OBJECTIVE: To assess whether data from internet-based social media and search engines are associated with objective clinic-based diagnoses of conjunctivitis. DESIGN, SETTING, AND PARTICIPANTS: Data from encounters of 4143 patients diagnosed with conjunctivitis from June 3, 2012, to April 26, 2014, at the University of California San Francisco (UCSF) Medical Center, were analyzed using Spearman rank correlation of each weekly observation to compare demographics and seasonality of nonallergic conjunctivitis with allergic conjunctivitis. Data for patient encounters with diagnoses for glaucoma and influenza were also obtained for the same period and compared with conjunctivitis. Temporal patterns of Twitter and Google web search data, geolocated to the United States and associated with these clinical diagnoses, were compared with the clinical encounters. The a priori hypothesis was that weekly internet-based searches and social media posts about conjunctivitis may reflect the true weekly clinical occurrence of conjunctivitis. MAIN OUTCOMES AND MEASURES: Weekly total clinical diagnoses at UCSF of nonallergic conjunctivitis, allergic conjunctivitis, glaucoma, and influenza were compared using Spearman rank correlation with equivalent weekly data on Tweets related to disease or disease-related keyword searches obtained from Google Trends. RESULTS: Seasonality of clinical diagnoses of nonallergic conjunctivitis among the 4143 patients (2364 females [57.1\%] and 1776 males [42.9\%]) with 5816 conjunctivitis encounters at UCSF correlated strongly with results of Google searches in the United States for the term pink eye (ρ, 0.68 [95\% CI, 0.52 to 0.78]; P \&lt; .001) and correlated moderately with Twitter results about pink eye (ρ, 0.38 [95\% CI, 0.16 to 0.56]; P \&lt; .001) and with clinical diagnosis of influenza (ρ, 0.33 [95\% CI, 0.12 to 0.49]; P \&lt; .001), but did not significantly correlate with seasonality of clinical diagnoses of allergic conjunctivitis diagnosis at UCSF (ρ, 0.21 [95\% CI, -0.02 to 0.42]; P = .06) or with results of Google searches in the United States for the term eye allergy (ρ, 0.13 [95\% CI, -0.06 to 0.32]; P = .19). Seasonality of clinical diagnoses of allergic conjunctivitis at UCSF correlated strongly with results of Google searches in the United States for the term eye allergy (ρ, 0.44 [95\% CI, 0.24 to 0.60]; P \&lt; .001) and eye drops (ρ, 0.47 [95\% CI, 0.27 to 0.62]; P \&lt; .001). CONCLUSIONS AND RELEVANCE: Internet-based search engine and social media data may reflect the occurrence of clinically diagnosed conjunctivitis, suggesting that these data sources can be leveraged to better understand the epidemiologic factors of conjunctivitis.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.2267},
	author = {Deiner, Michael S and Lietman, Thomas M and McLeod, Stephen D and Chodosh, James and Porco, Travis C}
}
@article {1589754,
	title = {Quantitative autofluorescence: Review of Current Technical Aspects and Applications in Chorioretinal Disease},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {346-350},
	abstract = {Purpose: In this review we discuss the broad clinical application of qAF and provide a descriptive summary of the phenotypic findings of different chorioretinal pathologies.Background: Quantitative Fundus autofluorescence (qAF) is a novel developing technology that can aid in diagnosis and longitudinal disease monitoring by measuring and comparing autofluorescence intensities. Fundus autofluorescence (FAF) is a noninvasive imaging method that creates a density map of the fluorophores of the ocular fundus and provides both functional and topographic anatomic information about retinal cells. Fluorophores are molecules that have the ability to temporarily absorb irradiated light, and emit a small amount of light of a different wavelength. Different endogenous fluorophores can be found in the ocular fundus. Changes in accumulation of retinal fluorophores usually indicate retinal pathology and create characteristic patterns of hyper-autofluorescence and hypo-autofluorescence that help establish a diagnosis.Conclusion: qAF allows a safe non-invasive visualization of the retina, enables a standard for AF intensities comparison and aids to the understanding of the genotype-phenotype correlations.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1908570},
	author = {Deitch, Iris and Ferenchak, Kevin and Miller, John B}
}
@article {1364600,
	title = {Role of shear-stress-induced VEGF expression in endothelial cell survival},
	journal = {J Cell Sci},
	volume = {125},
	number = {Pt 4},
	year = {2012},
	month = {2012 Feb 15},
	pages = {831-43},
	abstract = {Vascular endothelial growth factor (VEGF) plays a crucial role in developmental and pathological angiogenesis. Expression of VEGF in quiescent adult tissue suggests a potential role in the maintenance of mature blood vessels. We demonstrate, using a Vegf-lacZ reporter mouse model, that VEGF is expressed by arterial but not by venous or capillary endothelial cells (ECs) in vivo. Using an in vitro model, we show that arterial shear stress of human umbilical vein ECs (HUVECs) decreases apoptosis and increases VEGF expression, which is mediated by the induction of Kr{\"u}ppel-like factor 2 (KLF2). Additionally, shear stress stimulates the expression of VEGF receptor 2 (VEGFR2) and is associated with its activation. Knockdown of VEGF in shear stressed HUVECs blocks the protective effect of shear stress, resulting in EC apoptosis equivalent to that in control ECs cultured under static conditions. Similarly, treatment of ECs subjected to arterial shear stress with the VEGF receptor tyrosine kinase inhibitor SU1498, or VEGFR2 neutralizing antiserum, led to increased apoptosis, demonstrating that the mechanoprotection from increased shear is mediated by VEGFR2. Taken together, these studies suggest that arterial flow induces VEGF-VEGFR2 autocrine-juxtacrine signaling, which is a previously unidentified mechanism for vascular EC survival in adult arterial blood vessels.},
	keywords = {Animals, Arteries, Capillaries, Cell Survival, Endothelial Cells, Enzyme Activation, Female, Human Umbilical Vein Endothelial Cells, Humans, Kruppel-Like Transcription Factors, Male, Mice, Receptors, Vascular Endothelial Growth Factor, Stress, Mechanical, Up-Regulation, Vascular Endothelial Growth Factor A, Veins},
	issn = {1477-9137},
	doi = {10.1242/jcs.084301},
	author = {Dela Paz, Nathaniel G and Walshe, Tony E and Leach, Lyndsay L and Saint-Geniez, Magali and D{\textquoteright}Amore, Patricia A}
}
@article {1424802,
	title = {Predictors of Primary Intracranial Hypertension in Children Using a Newly Suggested Opening Pressure Cutoff of 280 mm HO},
	journal = {Pediatr Neurol},
	volume = {91},
	year = {2019},
	month = {2019 Feb},
	pages = {27-33},
	abstract = {OBJECTIVES: We assessed the clinical characteristics of primary intracranial hypertension (PIH) in children using a newly recommended threshold for cerebrospinal fluid opening pressure (280 mm HO). METHOD: Cross-sectional study of patients age <=21 years who had a lumbar puncture done for evaluation of PIH. Patients were excluded if lumbar puncture was done for a suspected infection, seizure, mental status changes, multiple sclerosis, or Guillain-Barre syndrome. Cases were identified using a text-search module followed by manual review. We performed χ2 analysis for categorical data and Mann-Whitney U test for continuous data, followed by a binary logistic regression. RESULTS: We identified 374 patients of whom 67\% were female, median age was 13 years interquartile range (11 to 16 years), and admission rate was 24\%. Using an opening pressure cutoff of 250 mm HO, 127 patients (34\%) were identified as having PIH, whereas using the new cutoff 105 patients (28\%) met PIH criteria. Predictors for PIH included optic disc edema or sixth nerve palsy using both old, odds ratio (OR) 7.6 (4.3, 13.5), and new cutoffs, OR 9.7 (95\% confidence interval 5.1, 18.5). Headache duration <=61 days is predictive of PIH using the new cutoff OR 4.1 (95\% confidence interval 1.3, 12.8). A model is presented which stratifies patients into groups with low (7\%), medium (18\%), and high (greater than 42\%) risk of PIH. CONCLUSIONS: A higher cerebrospinal fluid opening pressure threshold in the criteria of PIH is associated with PIH patients with a different symptom profile. Children with optic disc edema, bulging fontanel or sixth nerve palsy, are at increased risk for PIH.},
	issn = {1873-5150},
	doi = {10.1016/j.pediatrneurol.2018.09.013},
	author = {Delaney, Atima C and Velarde, Aynslee and Harper, Marvin B and Lebel, Alyssa and Landschaft, Assaf and Monuteaux, Michael and Heidary, Gena and Kimia, Amir A}
}
@article {1658650,
	title = {Mesenchymal Stromal/Stem Cell Extracellular Vesicles and Perinatal Injury: One Formula for Many Diseases},
	journal = {Stem Cells},
	volume = {40},
	number = {11},
	year = {2022},
	month = {2022 Nov 29},
	pages = {991-1007},
	abstract = {Over the past decades, substantial advances in neonatal medical care have increased the survival of extremely premature infants. However, there continues to be significant morbidity associated with preterm birth with common complications including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), neuronal injury such as intraventricular hemorrhage (IVH) or hypoxic ischemic encephalopathy (HIE), as well as retinopathy of prematurity (ROP). Common developmental immune and inflammatory pathways underlie the pathophysiology of such complications providing the opportunity for multisystem therapeutic approaches. To date, no single therapy has proven to be effective enough to prevent or treat the sequelae of prematurity. In the past decade mesenchymal stem/stromal cell (MSC)-based therapeutic approaches have shown promising results in numerous experimental models of neonatal diseases. It is now accepted that the therapeutic potential of MSCs is comprised of their secretome, and several studies have recognized the small extracellular vesicles (sEVs) as the paracrine vector. Herein, we review the current literature on the MSC-EVs as potential therapeutic agents in neonatal diseases and comment on the progress and challenges of their translation to the clinical setting.},
	issn = {1549-4918},
	doi = {10.1093/stmcls/sxac062},
	author = {Delavogia, Eleni and Ntentakis, Dimitrios P and Cortinas, John A and Fernandez-Gonzalez, Angeles and Alex Mitsialis, S and Kourembanas, Stella}
}
@article {560171,
	title = {PROSE Treatment for Ocular Chronic Graft-Versus-Host Disease as a Clinical Network Expands.},
	journal = {Eye Contact Lens},
	volume = {42},
	number = {4},
	year = {2016},
	month = {2016 Jul},
	pages = {262-6},
	abstract = {BACKGROUND: Keratoconjunctivitis sicca occurs in 40\% to 90\% of patients with ocular chronic graft-versus-host disease (cGVHD). Ocular symptoms can have profound effects in both the visual function and quality of life of patients with GVHD. We report the impact of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in patients with cGVHD as a clinical network expands. METHODS: We queried the BostonSight PROSE manufacturing database from January 2002 to December 2011. Patients treated for ocular cGVHD were reported by age, gender, year, and network site where the treatment was undertaken. The baseline and six-month follow-up scores of visual function using a standardized validated instrument, the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), were evaluated for a period in 2006 and again in 2010 after network expansion had occurred. RESULTS: A total of 407 patients with a male:female ratio of 226:181, mean age was 51 years with ocular cGVHD underwent PROSE treatment from January 2002 to December 2011. By 2011, 67\% of all cases were treated at network clinics. Baseline characteristics of patients treated throughout the network in 2010 were similar to that of 2006 and 2010 cohorts from the main center. There was a significant improvement of 41 points (P\&lt;0.001) in composite NEI VFQ score among patients treated across the network in 2010, similar to the improvement of 30 points (P\&lt;0.001) seen among the patients treated at the main center in 2010. There was a trend toward lower baseline self-reported general health status (SRGHS) and VFQ scores among patients treated at network clinics, suggesting that expansion of the network allows treatment of sicker patients (lower general health status) or those more severely affected by ocular cGVHD. CONCLUSIONS: PROSE treatment of ocular cGVHD has increased in the last decade with the establishment of BostonSight network clinics across the United States. Patients treated at network clinics showed similar levels of baseline visual function and SRGHS, and achieved a similar high level of improvement in visual function as those treated at the main center. Patient-reported measures of functional status are useful in evaluating treatment options for patients with cGVHD. PROSE treatment has significant positive impact on the visual function of patients with ocular cGVHD regardless of whether the patient is treated at the main center or at a network site.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000186},
	author = {DeLoss, Karen S and Le, Hong-Gam and Gire, Anisa and Chiu, Gloria B and Jacobs, Deborah S and Carrasquillo, Karen G}
}
@article {1466909,
	title = {Reply},
	journal = {Cornea},
	volume = {38},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {e56-e57},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002145},
	author = {Deng, Sophie X and Borderie, Vincent and Chan, Clara C and Dana, Reza and Figueiredo, Francisco C and Gomes, Jos{\'e} A P and Pellegrini, Graziella and Shimmura, Shigeto and Kruse, Friedrich E}
}
@article {1430525,
	title = {Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency},
	journal = {Cornea},
	volume = {38},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {364-375},
	abstract = {PURPOSE: Despite extensive knowledge gained over the last 3 decades regarding limbal stem cell deficiency (LSCD), the disease is not clearly defined, and there is lack of agreement on the diagnostic criteria, staging, and classification system among treating physicians and research scientists working on this field. There is therefore an unmet need to obtain global consensus on the definition, classification, diagnosis, and staging of LSCD. METHODS: A Limbal Stem Cell Working Group was first established by The Cornea Society in 2012. The Working Group was divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to obtain agreement on a strategic plan and methodology from all participants after a comprehensive literature search, and final agreement was reached on the definition, classification, diagnosis, and staging of LSCD. A writing group was formed to draft the current manuscript, which has been extensively revised to reflect the consensus of the Working Group. RESULTS: A consensus was reached on the definition, classification, diagnosis, and staging of LSCD. The clinical presentation and diagnostic criteria of LSCD were clarified, and a staging system of LSCD based on clinical presentation was established. CONCLUSIONS: This global consensus provides a comprehensive framework for the definition, classification, diagnosis, and staging of LSCD. The newly established criteria will aid in the correct diagnosis and formulation of an appropriate treatment for different stages of LSCD, which will facilitate a better understanding of the condition and help with clinical management, research, and clinical trials in this area.},
	keywords = {Consensus, Corneal Diseases, Epithelium, Corneal, Humans, Limbus Corneae, Stem Cells},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001820},
	author = {Deng, Sophie X and Borderie, Vincent and Chan, Clara C and Dana, Reza and Figueiredo, Francisco C and Gomes, Jos{\'e} A P and Pellegrini, Graziella and Shimmura, Shigeto and Kruse, Friedrich E and and The International Limbal Stem Cell Deficiency Working Group}
}
@article {1522716,
	title = {Global Consensus on the Management of Limbal Stem Cell Deficiency},
	journal = {Cornea},
	volume = {39},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {1291-1302},
	abstract = {PURPOSE: In recent decades, the medical and surgical treatment of limbal stem cell deficiency (LSCD) has evolved significantly through the incorporation of innovative pharmacological strategies, surgical techniques, bioengineering, and cell therapy. With such a wide variety of options, there is a need to establish a global consensus on the preferred approaches for the medical and surgical treatment of LSCD. METHODS: An international LSCD Working Group was established by the Cornea Society in 2012 and divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to reach agreement on a strategic plan and methods after a comprehensive literature search. A writing group drafted the current study. RESULTS: A consensus in the medical and surgical management of LSCD was reached by the Working Group. Optimization of the ocular surface by eyelid and conjunctival reconstruction, antiinflammatory therapy, dry eye and meibomian gland dysfunction treatment, minimization of ocular surface toxicity from medications, topical medications that promote epithelialization, and use of a scleral lens is considered essential before surgical treatment of LSCD. Depending on the laterality, cause, and stage of LSCD, surgical strategies including conjunctival epitheliectomy, amniotic membrane transplantation, transplantation of limbal stem cells using different techniques and sources (allogeneic vs. autologous vs. ex vivo-cultivated), transplantation of oral mucosal epithelium, and keratoprosthesis can be performed as treatment. A stepwise flowchart for use in treatment decision-making was established. CONCLUSIONS: This global consensus provides an up-to-date and comprehensive framework for the management of LSCD.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002358},
	author = {Deng, Sophie X and Kruse, Friedrich and Gomes, Jos{\'e} A P and Chan, Clara C and Daya, Sheraz and Dana, Reza and Figueiredo, Francisco C and Kinoshita, Shigeru and Rama, Paolo and Sangwan, Virender and Slomovic, Allan R and Tan, Donald and and The International Limbal Stem Cell Deficiency Working Group}
}
@article {1806601,
	title = {Trends in Anti-Vascular Endothelial Growth Factor Original Medicare Part B Claims in the United States, 2014-2019},
	journal = {Ophthalmic Epidemiol},
	year = {2024},
	month = {2024 Feb 05},
	pages = {1-10},
	abstract = {PURPOSE: To characterize trends in use of and expenditure for the intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept, ranibizumab, and bevacizumab among the population enrolled in Original Medicare from 2014 to 2019. METHODS: The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to extract Medicare Part B fee-for-service outpatient injection claims data submitted by ophthalmologists. Multivariable linear regression models were used to evaluate the association between reimbursement, ophthalmologist availability, and agent administration rate. RESULTS: Between 2014 and 2019, 17,588,995 intravitreal injection claims were filed by 4218 US ophthalmologists. Medicare costs for anti-VEGF injections increased from 2.51 B USD in 2014 to 4.02 B USD in 2019. Increased state-level ophthalmologist availability and incremental increases in average reimbursement amounts were found to be significantly associated with a 6.8-fold variation in 2019 overall anti-VEGF injection rates across states. CONCLUSIONS: Medicare injection rates and costs for anti-VEGF injections have both increased between 2014 and 2019, largely driven by increased aflibercept use. There is a significant association between ophthalmologist availability and anti-VEGF injection rate on the state level, suggesting access to care may contribute to the observed state-level disparities in intravitreal injection rates. Further characterization of factors contributing to the state-level variation in injection rates of individual anti-VEGF agents may help inform interventions promoting equitable access to and use of these drugs.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2024.2310854},
	author = {Desai, Sarishka and Sekimitsu, Sayuri and Rossin, Elizabeth J and Zebardast, Nazlee}
}
@article {1125286,
	title = {A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome},
	journal = {Nat Commun},
	volume = {8},
	year = {2017},
	month = {2017 Jul 06},
	pages = {16077},
	abstract = {Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk(insT/insT) zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits.},
	issn = {2041-1723},
	doi = {10.1038/ncomms16077},
	author = {Di Gioia, Silvio Alessandro and Connors, Samantha and Matsunami, Norisada and Cannavino, Jessica and Rose, Matthew F and Gilette, Nicole M and Artoni, Pietro and de Macena Sobreira, Nara Lygia and Chan, Wai-Man and Webb, Bryn D and Robson, Caroline D and Cheng, Long and Van Ryzin, Carol and Ramirez-Martinez, Andres and Mohassel, Payam and Leppert, Mark and Scholand, Mary Beth and Grunseich, Christopher and Ferreira, Carlos R and Hartman, Tyler and Hayes, Ian M and Morgan, Tim and Markie, David M and Fagiolini, Michela and Swift, Amy and Chines, Peter S and Speck-Martins, Carlos E and Collins, Francis S and Jabs, Ethylin Wang and B{\"o}nnemann, Carsten G and Olson, Eric N and Moebius Syndrome Research Consortium and Carey, John C and Robertson, Stephen P and Manoli, Irini and Engle, Elizabeth C}
}
@article {1318858,
	title = {Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies},
	journal = {Am J Hum Genet},
	volume = {103},
	number = {1},
	year = {2018},
	month = {2018 Jul 05},
	pages = {115-124},
	abstract = {MYF5 is member of the Myc-like basic helix-loop-helix transcription factor family and, in cooperation with other myogenic regulatory factors MYOD and MYF5, is a key regulator of early stages of myogenesis. Here, we report three consanguineous families with biallelic homozygous loss-of-function mutations in MYF5 who define a clinical disorder characterized by congenital ophthalmoplegia with scoliosis and vertebral and rib anomalies. The clinical phenotype overlaps strikingly with that reported in several Myf5 knockout mouse models. Affected members of two families share a haploidentical region that contains a homozygous 10\&nbsp;bp frameshift mutation in exon 1 of MYF5 (c.23_32delAGTTCTCACC [p.Gln8Leufs86]) predicted to undergo nonsense-mediated decay. Affected members of the third family harbor a homozygous missense change in exon 1 of MYF5 (c.283C\&gt;T [p.Arg95Cys]). Using in\&nbsp;vitro assays, we show that this missense mutation acts as a loss-of-function allele by impairing MYF5 DNA binding and nuclear localization. We performed whole-genome sequencing in one affected individual with the frameshift mutation and did not identify additional rare variants in the haploidentical region that might account for differences in severity among the families. These data support the direct role of MYF5 in rib, spine, and extraocular muscle formation in humans.},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2018.05.003},
	author = {Di Gioia, Silvio Alessandro and Shaaban, Sherin and T{\"u}ys{\"u}z, Beyhan and Elcioglu, Nursel H and Chan, Wai-Man and Robson, Caroline D and Ecklund, Kirsten and Gilette, Nicole M and Hamzaoglu, Azmi and Tayfun, Gulsen Akay and Traboulsi, Elias I and Engle, Elizabeth C}
}
@article {961676,
	title = {Management of High-risk Corneal Transplantation.},
	journal = {Surv Ophthalmol},
	year = {2016},
	month = {2016 Dec 21},
	abstract = {The cornea is the most commonly transplanted tissue in medicine. The main cause of corneal graft failure is allograft rejection. The incidence of graft rejection depends on the presence of high-risk characteristics, most notably corneal neovascularization. Although corneal grafting has a high success rates in the absence of these risk factors, high-risk keratoplasty is associated with low success rates because of a high incidence of immune-mediated graft rejection. To improve the survival of high-risk corneal transplantation, various preoperative, intraoperative, and postoperative measures can be considered.; however, the key step in the management of these grafts is the long-term use of local and/or systemic immunosuppressive agents. Although a number of immunosuppressive agents have been employed for this purpose, the results vary significantly across different studies. This is partly due to the lack of an optimized method for their use, as well as the lack of a precise stratification of the degree of risk in each individual patient. New targeted biologic treatments, as well as tolerance-inducing methods, show promising horizons in the management of high-risk corneal transplantation in near future.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.12.010},
	author = {Di Zazzo, Antonio and Kheirkhah, Ahmad and Abud, Tulio B and Goyal, Sunali and Dana, Reza}
}
@article {836806,
	title = {Ocular Manifestations of Inherited Phospholipase-Cγ2-Associated Antibody Deficiency and Immune Dysregulation.},
	journal = {Cornea},
	year = {2016},
	month = {2016 Jul 20},
	abstract = {PURPOSE: To report the ocular manifestations of phospholipase-Cγ2-associated antibody deficiency and immune dysregulation (PLAID). METHODS: Case report and literature review. RESULTS: A 21-year-old woman diagnosed with PLAID was referred for evaluation of repeated episodes of ocular inflammation resulting in bilateral peripheral corneal pannus with episcleritis and corneal scarring accompanied by systemic manifestations including epidermolysis bullosa and interstitial lung disease. Systemic immunosuppression with corticosteroids and interleukin-1 (IL-1) receptor antagonist (anakinra) was supplemented with topical anakinra to avoid systemic side effects, which resulted in partial improvement of the ocular symptoms. Oral prednisone was restarted to treat active lesions during bouts of inflammation. CONCLUSIONS: Ocular PLAID is a bilateral chronic or recurrent inflammatory disease of the ocular surface leading to severe and early cicatricial ocular surface and corneal involvement because of high IL-1 production. Management of PLAID may require both topical and systemic immunomodulatory treatments, potentially including targeted local anti-IL-1 therapy.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000951},
	author = {Di Zazzo, Antonio and Tahvildari, Maryam and Florakis, George J and Dana, Reza}
}
@article {1573119,
	title = {Corneal angiogenic privilege and its failure},
	journal = {Exp Eye Res},
	volume = {204},
	year = {2021},
	month = {2021 Mar},
	pages = {108457},
	abstract = {The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2021.108457},
	author = {Di Zazzo, Antonio and Gaudenzi, Daniele and Yin, Jia and Coassin, Marco and Fernandes, Merle and Dana, Reza and Bonini, Stefano}
}
@article {836811,
	title = {Proangiogenic Function of T Cells in Corneal Transplantation},
	journal = {Transplantation},
	volume = {101},
	number = {4},
	year = {2017},
	month = {2017 Apr},
	pages = {778-785},
	abstract = {BACKGROUND: Corneal neovascularization increases the risk of T cell-mediated allograft rejection. Here, we investigate whether T cells promote angiogenesis in transplantation. METHODS: Conventional effector T cells were collected from draining lymph nodes of allogeneic or syngeneic corneal transplanted BALB/c mice. T cells were either cocultured with vascular endothelial cells (VECs) to assess VEC proliferation or used in a mixed lymphocyte reaction assay. Messenger RNA (mRNA) expression of vascular endothelial growth factor (VEGF)-A, -C, and VEGF receptor 2 (VEGF-R2) in VECs was assessed by real-time PCR. VEGF-A protein expression was determined by enzyme-linked immunosorbent assay. Flow cytometry was used to analyze VEGF-R2 expression in corneal CD31 cells, and VEGF-A and IFNγ expression in corneal CD4 T cells. RESULTS: Allogeneic T cells from high-risk (HR) grafted mice induced more VEC proliferation than those from syngeneic transplant recipients (P = 0.03). Vascular endothelial growth factor-A mRNA and protein expression were higher in T cells from draining lymph nodes (P = 0.03 and P = 0.04, respectively) and cornea (protein; P = 0.04) of HR compared with low-risk (LR) grafted hosts. Vascular endothelial growth factor-A, VEGF-C, and VEGF-R2 mRNA expression were increased in VECs when cocultured with T cells from HR transplants compared with LR transplants and naive mice. In addition, IFNγ blockade in T cell/VEC coculture increased VEC proliferation and VEGF-A protein expression, whereas blocking VEGF-A significantly reduced VEC proliferation (P = 0.04). CONCLUSIONS: Allogeneic T cells from corneal transplant hosts promote VEC proliferation, probably via VEGF-A signaling, whereas IFNγ shows an antiangiogenic effect. Our data suggest that T cells are critical mediators of angiogenesis in transplantation.},
	issn = {1534-6080},
	doi = {10.1097/TP.0000000000001390},
	author = {Di Zazzo, Antonio and Tahvildari, Maryam and Subbarayal, Brinda and Yin, Jia and Dohlman, Thomas H and Inomata, Takenori and Mashaghi, Alireza and Chauhan, Sunil K and Dana, Reza}
}
@article {1263321,
	title = {Use of Topical Cannabinomimetic Palmitoylethanolamide in Ocular Surface Disease Associated with Antiglaucoma Medications},
	journal = {J Ocul Pharmacol Ther},
	volume = {33},
	number = {9},
	year = {2017},
	month = {2017 Nov},
	pages = {670-677},
	abstract = {PURPOSE: Chronic use of topical hypotensive therapies in glaucoma patients leads to chronic inflammation of the ocular surface, which decreases the success rate of long-term glaucoma management. The aim of this study is to evaluate the effect of topical palmitoylethanolamide (PEA) (Defluxa{\textcopyright}), a well-known anti-inflammatory and analgesic agent, in suppressing the ocular surface inflammation associated with the use of hypotensive eye drops. METHODS: In a pilot clinical trial, we enrolled 15 glaucomatous patients who received topical PEA (Defluxa) in addition to the current antiglaucoma drugs, while 15 glaucomatous patients did not receive any additional treatment. At 3 different time points (day 0, 15, and 30), signs of ocular surface involvement, adverse events, visual acuity, and intraocular pressure were assessed. RESULTS: Topical PEA (Defluxa) was effective in increasing the Schirmer test (P \&lt; 0.05) and the tear film breakup time (T-BUT) (P \&lt; 0.0001), and improving the conjunctival hyperemia (P \&lt; 0.0001) by day 30, compared to baseline. Compared to control, by day 15, the conjunctival hyperemia score was significantly decreased in the PEA (Defluxa) group (P \&lt; 0.01), while the T-BUT and the Schirmer Test achieved a significant improvement by day 30 (P \&lt; 0.05; P \&lt; 0.01). DISCUSSION: Our data suggests that topical PEA (Defluxa) is a safe, effective, and generally well-tolerated treatment to prevent or suppress ocular surface inflammation attributable to chronic glaucoma treatment.},
	issn = {1557-7732},
	doi = {10.1089/jop.2016.0117},
	author = {Di Zazzo, Antonio and Roberti, Gloria and Mashaghi, Alireza and Abud, Tulio Batista and Pavese, Daniela and Bonini, Stefano}
}
@article {1435399,
	title = {InflammAging at Ocular Surface: Clinical and Biomolecular Analyses in Healthy Volunteers},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {5},
	year = {2019},
	month = {2019 Apr 01},
	pages = {1769-1775},
	abstract = {Purpose: To assess the ocular surface in volunteers who consider themselves as healthy, in order to evaluate how para-inflammatory mechanisms fail with age, and thus investigate the phenomenon of "InflammAging." Methods: In this observational prospective cohort study, volunteers were categorized into three groups according to age: young (19-40 years), middle-aged (41-60 years), and older adults (61-93 years). Clinical assessments included tear breakup time (T-BUT) and Schirmer test type I. Dry eye symptoms were evaluated by the Ocular Surface Disease Index (OSDI) questionnaire. Conjunctival mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1), MUC5AC, and IL-8 were measured by real-time PCR and immunofluorescence. Results: A total of 82 volunteers (38 males and 44 females) were enrolled. T-BUT decreased significantly with increasing age (young: 11.13 {\textpm} 0.18 seconds; middle-aged: 10.83 {\textpm} 0.56 seconds; older: 9.00 {\textpm} 1.00 seconds, P \&lt; 0.05). Schirmer test values decreased significantly with age (young: 20.6 {\textpm} 1.0 mm; middle-aged: 19.2 {\textpm} 1.2 mm; older: 16.0 {\textpm} 1.1 mm, P \&lt; 0.05). OSDI scores increased with age in both groups, but they were substantially higher in women. Conjunctival expression of inflammatory markers ICAM-1, IL-8, and MUC5AC increased with age. Conclusions: Clinical signs, symptoms, and biomarkers of chronic inflammation increased with age in a cohort of volunteers who considered themselves healthy, indicating an age-related progressive impairment of ocular surface system function.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-25822},
	author = {Di Zazzo, Antonio and Micera, Alessandra and Coassin, Marco and Varacalli, Giuseppe and Foulsham, William and De Piano, Maria and Bonini, Stefano}
}
@article {1318859,
	title = {Imaging the Deep Choroidal Vasculature Using Spectral Domain and Swept Source Optical Coherence Tomography Angiography},
	journal = {J Vitreoretin Dis},
	volume = {2},
	number = {3},
	year = {2018},
	month = {2018 May-Jun},
	pages = {146-154},
	abstract = {Purpose: To evaluate the deeper choroidal vasculature in eyes with various ocular disorders using spectral domain (SD) optical coherence tomography angiography (OCTA) and swept source (SS) OCTA. Methods: Patients underwent OCTA imaging with either SD-OCTA (Zeiss Cirrus Angioplex or Optovue AngioVue) or SS-OCTA (Topcon Triton). Retinal pigment epithelium (RPE) integrity, structural visualization of deep choroidal vessels on en face imaging, and OCTA of deep choroidal blood flow signal were analyzed. Choroidal blood flow was deemed present if deeper choroidal vessels appeared bright after appropriate segmentation. Results: Structural visualization of choroidal vessels was feasible in all eyes by en face imaging. In both SD-OCTA and SS-OCTA, choroidal blood flow signal was present in all eyes with overlying RPE atrophy (100\% of eyes with RPE atrophy, 28.6\% of all imaged eyes, P \&lt; .001). Conclusions: While choroidal vessels can be visualized anatomically in all eyes by en face imaging, choroidal blood flow detection in deep choroidal vessel is largely restricted to areas with overlying RPE atrophy. Intact RPE acts as a barrier for reliable detection of choroidal flow using current OCTA technology, inhibiting evaluation of flow in deeper choroidal vessels in most eyes.},
	issn = {2474-1264},
	doi = {10.1177/2474126418771805},
	author = {Diaz, J Daniel and Wang, Jay C and Oellers, Patrick and Lains, In{\^e}s and Sobrin, Lucia and Husain, Deeba and Miller, Joan W and Vavvas, Demetrios G and Miller, John B}
}
@article {1698366,
	title = {Disentangling the genetic overlap and causal relationships between primary open-angle glaucoma, brain morphology and four major neurodegenerative disorders},
	journal = {EBioMedicine},
	volume = {92},
	year = {2023},
	month = {2023 Jun},
	pages = {104615},
	abstract = {BACKGROUND: Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by progressive degeneration of the optic nerve that leads to irreversible visual impairment. Multiple epidemiological studies suggest an association between POAG and major neurodegenerative disorders (Alzheimer{\textquoteright}s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Parkinson{\textquoteright}s disease). However, the nature of the overlap between neurodegenerative disorders, brain morphology and glaucoma remains inconclusive. METHOD: In this study, we performed a comprehensive assessment of the genetic and causal relationship between POAG and neurodegenerative disorders, leveraging genome-wide association data from studies of magnetic resonance imaging of the brain, POAG, and four major neurodegenerative disorders. FINDINGS: This study found a genetic overlap and causal relationship between POAG and its related phenotypes (i.e., intraocular pressure and optic nerve morphology traits) and brain morphology in 19 regions. We also identified 11 loci with a significant local genetic correlation and a high probability of sharing the same causal variant between neurodegenerative disorders and POAG or its related phenotypes. Of interest, a region on chromosome 17 corresponding to MAPT, a well-known risk locus for Alzheimer{\textquoteright}s and Parkinson{\textquoteright}s disease, was shared between POAG, optic nerve degeneration traits, and Alzheimer{\textquoteright}s and Parkinson{\textquoteright}s diseases. Despite these local genetic overlaps, we did not identify strong evidence of a causal association between these neurodegenerative disorders and glaucoma. INTERPRETATION: Our findings indicate a distinctive and likely independent neurodegenerative process for POAG involving several brain regions although several POAG or optic nerve degeneration risk loci are shared with neurodegenerative disorders, consistent with a pleiotropic effect rather than a causal relationship between these traits. FUNDING: PG was supported by an NHMRC Investigator Grant ($\#$1173390), SM by an NHMRC Senior Research Fellowship and an NHMRC Program Grant (APP1150144), DM by an NHMRC Fellowship, LP is funded by the NEIEY015473 and EY032559 grants, SS is supported by an NIH-Oxford Cambridge Fellowship and NIH T32 grant (GM136577), APK is supported by a UK Research and Innovation Future Leaders Fellowship, an Alcon Research Institute Young Investigator Award and a Lister Institute for Preventive Medicine Award.},
	keywords = {Alzheimer Disease, Brain, Genome-Wide Association Study, Glaucoma, Glaucoma, Open-Angle, Humans, Nerve Degeneration, Neurodegenerative Diseases, Parkinson Disease},
	issn = {2352-3964},
	doi = {10.1016/j.ebiom.2023.104615},
	author = {Diaz-Torres, Santiago and He, Weixiong and Thorp, Jackson and Seddighi, Sahba and Mullany, Sean and IGGC International Glaucoma Genetics Consortium and Hammond, Christopher J and Hysi, Pirro G and Pasquale, Louis R and Khawaja, Anthony P and Hewitt, Alex W and Craig, Jamie E and Mackey, David A and Wiggs, Janey L and van Duijn, Cornelia and Lupton, Michelle K and Ong, Jue-Sheng and Macgregor, Stuart and Gharahkhani, Puya}
}
@article {541271,
	title = {Mitochondrial DNA has a pro-inflammatory role in AMD.},
	journal = {Biochim Biophys Acta},
	volume = {1853},
	number = {11 Pt A},
	year = {2015},
	month = {2015 Nov},
	pages = {2897-906},
	abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly of industrialized nations, and there is increasing evidence to support a role for chronic inflammation in its pathogenesis. Mitochondrial DNA (mtDNA) has been recently reported to be pro-inflammatory in various diseases such as Alzheimer{\textquoteright}s and heart failure. Here, we report that intracellular mtDNA induces ARPE-19 cells to secrete inflammatory cytokines IL-6 and IL-8, which have been consistently associated with AMD onset and progression. The induction was dependent on the size of mtDNA, but not on specific sequence. Oxidative stress plays a major role in the development of AMD, and our findings indicate that mtDNA induces IL-6 and IL-8 more potently when oxidized. Cytokine induction was mediated by STING (Stimulator of Interferon Genes) and NF-κB as evidenced by abrogation of the cytokine response with the use of specific inhibitors (siRNA and BAY 11-7082, respectively). Finally, mtDNA primed the NLRP3 inflammasome. This study contributes to our understanding of the potential pro-inflammatory role of mtDNA in the pathogenesis of AMD.},
	issn = {0006-3002},
	doi = {10.1016/j.bbamcr.2015.08.012},
	author = {Dib, Bernard and Lin, Haijiang and Maidana, Daniel E and Tian, Bo and Miller, John B and Bouzika, Peggy and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1598034,
	title = {Photophobia: shared pathophysiology underlying dry eye disease, migraine and traumatic brain injury leading to central neuroplasticity of the trigeminothalamic pathway},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {751-760},
	abstract = {BACKGROUND: Photophobia is a potentially debilitating symptom often found in dry eye disease (DE), migraine and traumatic brain injury (TBI). METHODS: We conducted a review of the literature via a PubMed search of English language articles with a focus on how photophobia may relate to a shared pathophysiology across DE, migraine and TBI. RESULTS: DE, migraine and TBI are common conditions in the general population, are often comorbid, and share photophobia as a symptom. Across the three conditions, neural dysregulation of peripheral and central nervous system components is implicated in photophobia in various animal models and in humans. Enhanced activity of the neuropeptide calcitonin gene-related peptide (CGRP) is closely linked to photophobia. Current therapies for photophobia include glasses which shield the eyes from specific wavelengths, botulinum toxin, and inhibition of CGRP and its receptor. Many individuals have persistent photophobia despite the use of these therapies, and thus, development of new therapies is needed. CONCLUSIONS: The presence of photophobia in DE, migraine and TBI suggests shared trigeminothalamic pathophysiologic mechanisms, as explained by central neuroplasticity and hypersensitivity mediated by neuropeptide CGRP. Treatment strategies which target neural pathways (ie, oral neuromodulators, transcutaneous nerve stimulation) should be considered in patients with persistent photophobia, specifically in individuals with DE whose symptoms are not controlled with traditional therapies.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316417},
	author = {Diel, Ryan J and Mehra, Divy and Kardon, Randy and Buse, Dawn C and Moulton, Eric and Galor, Anat}
}
@article {1363269,
	title = {The influence of 13-cis retinoic acid on human meibomian gland epithelial cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {6},
	year = {2013},
	month = {2013 Jun 26},
	pages = {4341-50},
	abstract = {PURPOSE: Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells. METHODS: To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated. RESULTS: We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9. CONCLUSIONS: Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA-related induction of MGD.},
	keywords = {Cell Death, Cell Line, Transformed, Cell Proliferation, Cell Survival, Dermatologic Agents, Dose-Response Relationship, Drug, Dry Eye Syndromes, Epithelial Cells, Gene Expression, Humans, In Situ Nick-End Labeling, Interleukin-1beta, Isotretinoin, Matrix Metalloproteinase 9, Meibomian Glands, Proto-Oncogene Proteins c-akt, Signal Transduction},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-11863},
	author = {Ding, Juan and Kam, Wendy R and Dieckow, Julia and Sullivan, David A}
}
@article {1351157,
	title = {The effects of insulin-like growth factor 1 and growth hormone on human meibomian gland epithelial cells},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {5},
	year = {2014},
	month = {2014 May},
	pages = {593-9},
	abstract = {IMPORTANCE: A phase 1 study has reported that dry eye disease is the most common adverse effect of human exposure to the antibody figitumumab, an anticancer drug that prevents insulin-like growth factor 1 (IGF-1) from binding to its receptor. We hypothesized that the mechanism underlying this effect is the inhibition of IGF-1 action in epithelial cells of the meibomian gland. OBJECTIVES: To test the hypothesis that IGF-1 stimulates meibomian gland function in vitro and to examine whether growth hormone, a closely related hormone of IGF-1, has the same effect. DESIGN, SETTING, AND MATERIAL: Immortalized human meibomian gland epithelial cells were cultured in the presence or the absence of IGF-1, growth hormone, and an IGF-1 receptor-blocking antibody. Signaling pathways, cell proliferation, neutral lipid staining, and a key protein involved in lipid biogenesis were evaluated. INTERVENTION: Application of IGF-1 and growth hormone to human meibomian gland epithelial cells. MAIN OUTCOMES AND MEASURES: Immunoblotting, cell counting, and neutral lipid staining. RESULTS Insulin-like growth factor 1 activated the phosphoinositol 3-kinase/Akt and forkhead box O1 pathways (showing a dose-dependent effect on immunoblotting), stimulated cellular proliferation (about 1.8-fold increase in cell number), increased sterol regulatory element-binding protein 1 expression (about 3-fold increase on immunoblotting), and promoted lipid accumulation in human meibomian gland epithelial cells (about 2-fold increase in lipid staining). These IGF-1 actions, which may be blocked by cotreatment with the anti-IGF-1 antibody, were accompanied by inconsistent effects on extracellular signal-regulated kinase phosphorylation. We were not able to demonstrate activation of Akt, forkhead box O1, extracellular signal-regulated kinase, Janus kinase 2, or signal transducers and activators of transcription 5, induced cell proliferation, or lipid accumulation in these cells by growth hormone application. CONCLUSIONS AND RELEVANCE: Our results support the hypothesis that IGF-1 acts on human meibomian gland epithelial cells and may explain why treatment with figitumumab, the IGF-1 inhibitor, causes dry eye disease. Ophthalmic care for dry eye disease may be needed when patients with cancer undergo treatment with drugs that inhibit IGF-1 action.},
	keywords = {Antibodies, Monoclonal, Cell Count, Cell Survival, Cells, Cultured, Dry Eye Syndromes, Electrophoresis, Polyacrylamide Gel, Epithelial Cells, Female, Growth Hormone, Humans, Immunoblotting, Insulin-Like Growth Factor I, Male, Meibomian Glands, Signal Transduction},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.8295},
	author = {Ding, Juan and Sullivan, David A}
}
@article {1363270,
	title = {Mouse models of growth hormone action and aging: a proteomic perspective},
	journal = {Proteomics},
	volume = {13},
	number = {3-4},
	year = {2013},
	month = {2013 Feb},
	pages = {674-85},
	abstract = {Growth hormone (GH) is a protein secreted by the anterior pituitary and circulates throughout the body to exert important actions on growth and metabolism. GH stimulates the secretion of insulin-like growth factor-I (IGF-I) that mediates some of the growth promoting actions of GH. The GH/IGF-I axis has recently been recognized as important in terms of longevity in organisms ranging from Caenorhabditis elegans to mice. For example, GH transgenic mice possess short lifespans while GH receptor null (GHR-/-) mice have extended longevity. Thus, the actions of GH (or IGF-I) or lack thereof impact the aging process. In this review, we summarize the proteomic analyses of plasma and white adipose tissue in these two mouse models of GH action, i.e. GH transgenic and GHR-/- mice. At the protein level, we wanted to establish novel plasma biomarkers of GH action as a function of age and to determine differences in adipose tissue depots. We have shown that these proteomic approaches have not only confirmed several known physiological actions of GH, but also resulted in novel protein biomarkers and targets that may be indicative of the aging process and/or new functions of GH. These results may generate new directions for GH and/or aging research.},
	keywords = {Adipose Tissue, White, Aging, Animals, Blood Proteins, Gene Knockout Techniques, Growth Hormone, Humans, Insulin, Insulin Resistance, Insulin-Like Growth Factor I, Lipid Metabolism, Proteome, Proteomics, Receptors, Somatotropin},
	issn = {1615-9861},
	doi = {10.1002/pmic.201200271},
	author = {Ding, Juan and Sackmann-Sala, Lucila and Kopchick, John J}
}
@article {1347434,
	title = {Diet quality and genetic association with body mass index: results from 3 observational studies},
	journal = {Am J Clin Nutr},
	volume = {108},
	number = {6},
	year = {2018},
	month = {2018 Dec 01},
	pages = {1291-1300},
	abstract = {Background: It is unknown whether dietary quality modifies genetic association with body mass index (BMI). Objective: This study examined whether dietary quality modifies genetic association with BMI. Design: We calculated 3 diet quality scores including the Alternative Healthy Eating Index 2010 (AHEI-2010), the Alternative Mediterranean Diet score (AMED), and the Dietary Approach to Stop Hypertension (DASH) diet score. We examined the interactions of a genetic risk score (GRS) based on 97 BMI-associated variants with the 3 diet quality scores on BMI in 30,904 participants from 3 large cohorts. Results: We found significant interactions between total GRS and all 3 diet scores on BMI assessed after 2-3 y, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P-interaction\&nbsp;=\&nbsp;0.003; AMED: P\&nbsp;=\&nbsp;0.001; DASH: P\&nbsp;=\&nbsp;0.004). For example, the difference in BMI (kg/m2) per 10-unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared with those in the lowest tertile (0.84; 95\% CI: 0.72, 0.96 compared with 1.14; 95\% CI: 0.99, 1.29). Results were consistent across the 3 cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for central nervous system GRSs (P\&nbsp;\&lt;\&nbsp;0.01 for 3 diet scores) than for non-central nervous system GRSs (P\&nbsp;\&gt;\&nbsp;0.05 for 3 diet scores). Conclusions: A higher diet quality attenuated genetic predisposition to obesity. These findings underscore the importance of maintaining a healthful diet for the prevention of obesity, particularly for those individuals with a strong genetic predisposition to obesity. This trial was registered with the Clinical Trial Registry as NCT03577639.},
	issn = {1938-3207},
	doi = {10.1093/ajcn/nqy203},
	author = {Ding, Ming and Ellervik, Christina and Huang, Tao and Jensen, Majken K and Curhan, Gary C and Pasquale, Louis R and Kang, Jae H and Wiggs, Janey L and Hunter, David J and Willett, Walter C and Rimm, Eric B and Kraft, Peter and Chasman, Daniel I and Qi, Lu and Hu, Frank B and Qi, Qibin}
}
@article {1364601,
	title = {Aging and dry eye disease},
	journal = {Exp Gerontol},
	volume = {47},
	number = {7},
	year = {2012},
	month = {2012 Jul},
	pages = {483-90},
	abstract = {Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD.},
	keywords = {Aging, Animals, Disease Models, Animal, Dry Eye Syndromes, Humans, Meibomian Glands, Retinoids},
	issn = {1873-6815},
	doi = {10.1016/j.exger.2012.03.020},
	author = {Ding, Juan and Sullivan, David A}
}
@article {397791,
	title = {Human growth hormone promotes corneal epithelial cell migration in vitro.},
	journal = {Cornea},
	volume = {34},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {686-92},
	abstract = {PURPOSE: Corneal wound healing is a highly regulated process that requires the proliferation and migration of epithelial cells and interactions between epithelial cells and stromal fibroblasts. Compounds that can be applied topically to the ocular surface and that have the capability of activating corneal epithelial cells to proliferate and/or migrate would be useful to promote corneal wound healing. We hypothesize that human growth hormone (HGH) will activate signal transducers and activators of transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial cell and fibroblast proliferation and/or migration in vitro. The purpose of this study was to test these hypotheses. METHODS: We studied cell signaling, proliferation, and migration using an immortalized human corneal epithelial cell line and primary human corneal fibroblasts in vitro. We also examined whether insulin-like growth factor-1 (IGF-1), a hormone known to mediate many of HGH{\textquoteright}s growth promoting actions, may play a role in this effect. RESULTS: We show that HGH activates STAT5 signaling and promotes corneal epithelial cell migration in vitro. The migratory effect requires an intact communication between corneal epithelia and fibroblasts and is not mediated by IGF-1. CONCLUSIONS: HGH may represent a topical therapeutic to promote corneal epithelial wound healing. This warrants further investigation.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000418},
	author = {Ding, Juan and Wirostko, Barbara and Sullivan, David A}
}
@article {1762011,
	title = {FEAST: A flow cytometry-based toolkit for interrogating microglial engulfment of synaptic and myelin proteins},
	journal = {Nat Commun},
	volume = {14},
	number = {1},
	year = {2023},
	month = {2023 Sep 27},
	pages = {6015},
	abstract = {Although engulfment is a hallmark of microglia function, fully validated platforms that facilitate high-throughput quantification of this process are lacking. Here, we present FEAST (Flow cytometric Engulfment Assay for Specific Target proteins), which enables interrogation of in vivo engulfment of synaptic material by brain resident macrophages at single-cell resolution. We optimize FEAST for two different analyses: quantification of fluorescent material inside live cells and of engulfed endogenous proteins within fixed cells. To overcome false-positive engulfment signals, we introduce an approach suitable for interrogating engulfment in microglia from perfusion-fixed tissue. As a proof-of-concept for the specificity and versatility of FEAST, we examine the engulfment of synaptic proteins after optic nerve crush and of myelin in two mouse models of demyelination (treatment with cuprizone and injections of lysolecithin). We find that microglia, but not brain-border\&nbsp;associated macrophages, engulf in these contexts. Our work underscores how FEAST can be utilized to gain critical insight into functional neuro-immune interactions that shape development, homeostasis, and disease.},
	keywords = {Animals, Flow Cytometry, Macrophages, Mice, Microglia, Myelin Proteins, Myelin Sheath},
	issn = {2041-1723},
	doi = {10.1038/s41467-023-41448-7},
	author = {Lasse Dissing-Olesen and Walker, Alec J and Feng, Qian and Barr, Helena J and Walker, Alicia C and Xie, Lili and Daniel K Wilton and Das, Indrani and Benowitz, Larry I and Beth Stevens}
}
@article {1559554,
	title = {Assessing Glaucoma Progression Using Machine Learning Trained on Longitudinal Visual Field and Clinical Data},
	journal = {Ophthalmology},
	volume = {128},
	number = {7},
	year = {2021},
	month = {2021 Jul},
	pages = {1016-1026},
	abstract = {PURPOSE: Rule-based approaches to determining glaucoma progression from visual fields (VFs) alone are discordant and have tradeoffs. To detect better when glaucoma progression is occurring, we used a longitudinal data set of merged VF and clinical data to assess the performance of a convolutional long short-term memory (LSTM) neural network. DESIGN: Retrospective analysis of longitudinal clinical and VF data. PARTICIPANTS: From 2 initial datasets of 672 123 VF results from 213 254 eyes and 350 437 samples of clinical data, persons at the intersection of both datasets with 4 or more VF results and corresponding baseline clinical data (cup-to-disc ratio, central corneal thickness, and intraocular pressure) were included. After exclusion criteria-specifically the removal of VFs with high false-positive and false-negative rates and entries with missing data-were applied to ensure reliable data, 11 242 eyes remained. METHODS: Three commonly used glaucoma progression algorithms (VF index slope, mean deviation slope, and pointwise linear regression) were used to define eyes as stable or progressing. Two machine learning models, one exclusively trained on VF data and another trained on both VF and clinical data, were tested. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AUPRC) calculated on a held-out test set and mean accuracies from threefold cross-validation were used to compare the performance of the machine learning models. RESULTS: The convolutional LSTM network demonstrated 91\% to 93\% accuracy with respect to the different conventional glaucoma progression algorithms given 4 consecutive VF results for each participant. The model that was trained on both VF and clinical data (AUC, 0.89-0.93) showed better diagnostic ability than a model exclusively trained on VF results (AUC, 0.79-0.82; P \&lt; 0.001). CONCLUSIONS: A convolutional LSTM architecture can capture local and global trends in VFs over time. It is\&nbsp;well suited to assessing glaucoma progression because of its ability to extract spatiotemporal features that\&nbsp;other algorithms cannot. Supplementing VF results with clinical data improves the model{\textquoteright}s ability to assess glaucoma progression and better reflects the way clinicians manage data when managing glaucoma.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.12.020},
	author = {Dixit, Avyuk and Yohannan, Jithin and Boland, Michael V}
}
@article {1517176,
	title = {Implementation and Impact of a Store-and-Forward Teledermatology Platform in an Urban Academic Safety-Net Health Care System},
	journal = {Telemed J E Health},
	volume = {27},
	number = {3},
	year = {2021},
	month = {2021 03},
	pages = {308-315},
	abstract = {. . . . .},
	issn = {1556-3669},
	doi = {10.1089/tmj.2020.0069},
	author = {Dobry, Allison and Begaj, Tedi and Mengistu, Kira and Sinha, Sumi and Droms, Rebecca and Dunlap, Rachel and Wu, Dominic and Adhami, Katayun and Stavert, Robert}
}
@article {1359926,
	title = {MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance},
	journal = {Am J Hum Genet},
	volume = {103},
	number = {6},
	year = {2018},
	month = {2018 Dec 06},
	pages = {1009-1021},
	abstract = {To date, mutations in 15 actin- or microtubule-associated genes have been associated with the cortical malformation lissencephaly and variable brainstem hypoplasia. During a multicenter review, we recognized a rare lissencephaly variant with a complex brainstem malformation in three unrelated children. We searched our large brain-malformation databases and found another five children with this malformation (as well as one with a less severe variant), analyzed available whole-exome or -genome sequencing data, and tested ciliogenesis in two affected individuals. The brain malformation comprised posterior predominant lissencephaly and midline crossing defects consisting of absent anterior commissure and a striking W-shaped brainstem malformation caused by small or absent pontine crossing fibers. We discovered heterozygous de novo missense variants or an in-frame deletion involving highly conserved zinc-binding residues within the GAR domain of MACF1 in the first eight subjects. We studied cilium formation and found a higher proportion of mutant cells with short cilia than of control cells with short cilia. A ninth child had similar lissencephaly but\&nbsp;only subtle brainstem dysplasia associated with a heterozygous de novo missense variant in the spectrin repeat domain of MACF1. Thus, we report variants of the microtubule-binding GAR domain of MACF1 as the cause of a distinctive and most likely pathognomonic brain malformation. A\&nbsp;gain-of-function or dominant-negative mechanism appears likely given that many heterozygous mutations leading to protein truncation are included in the ExAC Browser. However, three de novo variants in MACF1 have been observed in large schizophrenia cohorts.},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2018.10.019},
	author = {Dobyns, William B and Aldinger, Kimberly A and Ishak, Gisele E and Mirzaa, Ghayda M and Timms, Andrew E and Grout, Megan E and Dremmen, Marjolein H G and Schot, Rachel and Vandervore, Laura and van Slegtenhorst, Marjon A and Wilke, Martina and Kasteleijn, Esmee and Lee, Arthur S and Barry, Brenda J and Chao, Katherine R and Szcza{\l}uba, Krzysztof and Kobori, Joyce and Hanson-Kahn, Andrea and Bernstein, Jonathan A and Carr, Lucinda and D{\textquoteright}Arco, Felice and Miyana, Kaori and Okazaki, Tetsuya and Saito, Yoshiaki and Sasaki, Masayuki and Das, Soma and Wheeler, Marsha M and Bamshad, Michael J and Nickerson, Deborah A and University of Washington Center for Mendelian Genomics and Center for Mendelian Genomics at the Broad Institute of MIT and Harvard and Engle, Elizabeth C and Verheijen, Frans W and Doherty, Dan and Mancini, Grazia M S}
}
@article {1538327,
	title = {The Use of Mobile Applications as Low-Vision Aids: A Pilot Study},
	journal = {R I Med J (2013)},
	volume = {103},
	number = {8},
	year = {2020},
	month = {2020 Oct 01},
	pages = {69-72},
	abstract = {OBJECTIVE: To determine the most commonly used and highest-rated mobile applications (apps) for low-vision aids. METHODS: This was a convenience sample survey. Patients known to use low-vision apps at a nonprofit low-vision center (INSIGHT, Warwick, RI) were contacted by phone between June and September 2019. INCLUSION CRITERIA: age 18+, Snellen visual acuity (VA) below 20/70, and the use of low-vision mobile apps for at least one month. A standardized script was used to record survey data and app ratings were evaluated by patients with a scale of one to five, one being the lowest and five being the highest. RESULTS: Of the sample (n=11), nine patients (81.8\%) stated they used an iPhone for low-vision mobile apps. A list of 14 mobile apps was identified: the two most commonly used apps were Seeing AI (81.8\%) and Be My Eyes (63.6\%); their average ratings were 4.43/5 and 4.75/5, respectively. CONCLUSIONS: This survey suggests that Seeing AI and Be My Eyes are useful apps to help low- vision patients with activities of daily living.},
	issn = {2327-2228},
	author = {Dockery, Dominique M and Krzystolik, Magdalena G}
}
@article {1511493,
	title = {The Ocular Manifestations and Transmission of COVID-19: Recommendations for Prevention},
	journal = {J Emerg Med},
	year = {2020},
	month = {2020 May 08},
	abstract = {BACKGROUND: Coronavirus disease-2019 (COVID-19), caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been linked to ocular signs and symptoms in several case reports. Research has demonstrated that SARS-CoV-2 is spread primarily through close contact via respiratory droplets, but there is the possibility for ocular transmission, with the conjunctiva as a conduit as well as a source of infection. DISCUSSION: Ocular manifestations of SARS-CoV-2 include follicular conjunctivitis, and have been repeatedly noted as an initial or subsequent symptom of COVID-19-positive patients. Particularly in patients with ocular manifestations, there is evidence that the virus may present in tears, based on the detection of SARS-CoV-2 in conjunctival swab samples via reverse transcription polymerase chain reaction. The virus may therefore be transmittable from the ocular surface to a new host via contact with the ocular mucosa, tears, or subsequent fomites. CONCLUSIONS: All health care professionals should ask patients about ocular symptoms consistent with SARS-CoV-2, and use eye protection such as goggles or face shields as part of the standard personal protective equipment for high-risk patients in addition to wearing of masks by both the patient and provider, and should consider tears to be potentially infectious.},
	issn = {0736-4679},
	doi = {10.1016/j.jemermed.2020.04.060},
	author = {Dockery, Dominique M and Rowe, Susannah G and Murphy, Marjorie A and Krzystolik, Magdalena G}
}
@article {1580512,
	title = {Infant with inability to abduct left eye},
	journal = {J Am Coll Emerg Physicians Open},
	volume = {2},
	number = {1},
	year = {2021},
	month = {2021 Feb},
	pages = {e12381},
	issn = {2688-1152},
	doi = {10.1002/emp2.12381},
	author = {Dodderer, Joshua K and Meyer, Erin and McAnally, Meghan and Falcone, Michelle M and Sundberg, Melissa and Nihalani, Bharti R}
}
@article {541336,
	title = {Hazard detection with a monocular bioptic telescope.},
	journal = {Ophthalmic Physiol Opt},
	volume = {35},
	number = {5},
	year = {2015},
	month = {2015 Sep},
	pages = {530-9},
	abstract = {PURPOSE: The safety of bioptic telescopes for driving remains controversial. The ring scotoma, an area to the telescope eye due to the telescope magnification, has been the main cause of concern. This study evaluates whether bioptic users can use the fellow eye to detect in hazards driving videos that fall in the ring scotoma area. METHODS: Twelve visually impaired bioptic users watched a series of driving hazard perception training videos and responded as soon as they detected a hazard while reading aloud letters presented on the screen. The letters were placed such that when reading them through the telescope the hazard fell in the ring scotoma area. Four conditions were tested: no bioptic and no reading, reading without bioptic, reading with a bioptic that did not occlude the fellow eye (non-occluding bioptic), and reading with a bioptic that partially-occluded the fellow eye. Eight normally sighted subjects performed the same task with the partially occluding bioptic detecting lateral hazards (blocked by the device scotoma) and vertical hazards (outside the scotoma) to further determine the cause-and-effect relationship between hazard detection and the fellow eye. RESULTS: There were significant differences in performance between conditions: 83\% of hazards were detected with no reading task, dropping to 67\% in the reading task with no bioptic, to 50\% while reading with the non-occluding bioptic, and 34\% while reading with the partially occluding bioptic. For normally sighted, detection of vertical hazards (53\%) was significantly higher than lateral hazards (38\%) with the partially occluding bioptic. CONCLUSIONS: Detection of driving hazards is impaired by the addition of a secondary reading like task. Detection is further impaired when reading through a monocular telescope. The effect of the partially-occluding bioptic supports the role of the non-occluded fellow eye in compensating for the ring scotoma.},
	issn = {1475-1313},
	doi = {10.1111/opo.12232},
	author = {Doherty, Amy L and Peli, Eli and Luo, Gang}
}
@article {1445323,
	title = {Evaluation of signs and symptoms of ocular surface disease after intravitreal injection},
	journal = {Acta Ophthalmol},
	volume = {97},
	number = {8},
	year = {2019},
	month = {2019 Dec},
	pages = {e1154-e1156},
	issn = {1755-3768},
	doi = {10.1111/aos.14146},
	author = {Dohlman, Thomas H and Lertsuwanroj, Buntitar and D{\textquoteright}Amico, Donald J and Ciralsky, Jessica B and Kiss, Szil{\'a}rd}
}
@article {399186,
	title = {VEGF-trap Aflibercept Significantly Improves Long-term Graft Survival in High-risk Corneal Transplantation.},
	journal = {Transplantation},
	volume = {99},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {678-86},
	abstract = {BACKGROUND: Graft failure because of immune rejection remains a significant problem in organ transplantation, and lymphatic and blood vessels are important components of the afferent and efferent arms of the host alloimmune response, respectively. We compare the effect of antihemangiogenic and antilymphangiogenic therapies on alloimmunity and graft survival in a murine model of high-risk corneal transplantation. METHODS: Orthotopic corneal transplantation was performed in hemevascularized and lymph-vascularized high-risk host beds, and graft recipients received subconjunctival vascular endothelial growth factor (VEGF)-trap, anti-VEGF-C, sVEGFR-3, or no treatment, beginning at the time of surgery. Fourteen days after transplantation, graft hemeangiogenesis and lymphangiogenesis were evaluated by immunohistochemistry. The frequencies of Th1 cells in regional lymphoid tissue and graft-infiltrating immune cells were evaluated by flow cytometry. Long-term allograft survival was compared using Kaplan-Meier curves. RESULTS: VEGF-trap significantly decreased graft hemangiogenesis as compared to the control group and was most effective in reducing the frequency of graft-infiltrating immune cells. Anti-VEGF-C and sVEGFR3 significantly decreased graft lymphangiogenesis and lymphoid Th1 cell frequencies as compared to control. VEGF-trap (72\%), anti-VEGF-C (25\%), and sVEGFR-3 (11\%) all significantly improved in the 8-week graft survival compared to control (0\%), although VEGF-trap was significantly more effective than both anti-VEGF-C (P \&lt; 0.05) and sVEGFR-3 (P \&lt; 0.05). CONCLUSION: In a clinically relevant model of high-risk corneal transplantation in which blood and lymphatic vessels are present and treatment begins at the time of transplantation, VEGF-trap is significantly more effective in improving long-term graft survival as compared to anti-VEGF-C and sVEGFR-3, but all approaches improve survival when compared to untreated control.},
	issn = {1534-6080},
	doi = {10.1097/TP.0000000000000512},
	author = {Dohlman, Thomas H and Omoto, Masahiro and Hua, Jing and Stevenson, William and Lee, Sang-Mok and Chauhan, Sunil K and Dana, Reza}
}
@article {1664957,
	title = {The Impact of Strabismus on Psychosocial Equity},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {52-56},
	abstract = {Strabismus, the condition of misaligned eyes, can result in severe, long-lasting functional and psychosocial sequelae. This review examines existing literature that has described and quantified the psychosocial consequences of strabismus. In particular, the role of strabismus in creating social, psychological, and vocational disparities, and how these intersect with race, ethnicity, and gender, is described. The reviewed data suggest that negative perceptions of strabismus are formed early in life. Overall, exotropia is more easily noticed than esotropia. Esotropia is perceived more negatively than exotropia, and there is significant variation with respect to gender, racial, and ethnic groups. The data demonstrate that the presence of strabismus affects self-esteem, interpersonal relationships, and access to vocational opportunities. Surgical correction of strabismus has been shown to provide significant and long-lasting improvements in psychosocial well-being.},
	keywords = {Esotropia, Exotropia, Eye Abnormalities, Humans, Strabismus},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152701},
	author = {Dohlman, Jenny C and Hunter, David G and Heidary, Gena}
}
@article {1532380,
	title = {COVID-19 and Ophthalmologic Education: A Call to Innovate},
	journal = {Am J Ophthalmol},
	volume = {220},
	year = {2020},
	month = {2020 12},
	pages = {A12-A13},
	keywords = {COVID-19, Delivery of Health Care, Humans, Ophthalmology, Organizational Innovation, Pandemics, SARS-CoV-2},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.06.045},
	author = {Dohlman, Jenny C}
}
@article {655056,
	title = {E-Selectin Mediates Immune Cell Trafficking in Corneal Transplantation.},
	journal = {Transplantation},
	volume = {100},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {772-80},
	abstract = {BACKGROUND: Immune rejection continues to threaten all tissue transplants. Here we sought to determine whether platelet (P)- and endothelial (E)-selectin mediate T cell recruitment in corneal transplantation and whether their blockade can reduce T cell graft infiltration and improve long-term corneal allograft survival. METHODS: In a murine model of allogeneic corneal transplantation, we used PCR and immunohistochemistry to investigate expression of P- and E-selectin in rejected versus accepted allografts and lymph node flow cytometry to assess expression of selectin ligands by effector T cells. Using P- and E-selectin neutralizing antibodies, we evaluated the effect of blockade on CD4 T cell recruitment, as well as the effect of anti-E-selectin on long-term allograft survival. RESULTS: The P- (93.3-fold, P \&lt; 0.05) and E-selectin (17.1-fold, P \&lt; 0.005) are upregulated in rejected versus accepted allogeneic transplants. Type 1 T helper cells from hosts with accepted and rejected grafts express high levels of P-selectin glycoprotein ligand 1 and glycosylated CD43. In vivo blockade of P (0.47 {\textpm} 0.03, P \&lt; 0.05) and E selectin (0.49 {\textpm} 0.1, P \&lt; 0.05) reduced the number of recruited T cells compared with IgG control (0.98 {\textpm} 0.1). Anti-E-selectin reduced the number of mature antigen-presenting cells trafficking to lymphoid tissue compared with control (6.96 {\textpm} 0.9 vs 12.67 {\textpm} 0.5, P \&lt; 0.05). Anti-E-selectin treatment delayed graft rejection and increased survival compared with control, although this difference did not reach statistical significance. CONCLUSIONS: In a model of corneal transplantation, P- and E-selectin mediate T cell recruitment to the graft, E-selectin mediates APC trafficking to lymphoid tissue, and blockade of E-selectin has a modest effect on improving long-term graft survival.},
	issn = {1534-6080},
	doi = {10.1097/TP.0000000000001107},
	author = {Dohlman, Thomas H and Di Zazzo, Antonio and Omoto, Masahiro and Hua, Jing and Ding, Julia and Hamrah, Pedram and Chauhan, Sunil K and Dana, Reza}
}
@article {1483608,
	title = {Sequential Bilateral Subperiosteal Hematomas},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {36},
	number = {6},
	year = {2020},
	month = {2020 Nov/Dec},
	pages = {e162},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001595},
	author = {Dohlman, Jenny C and Wolkow, Natalie and Yoon, Michael K}
}
@article {1651369,
	title = {Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial},
	journal = {Ophthalmology},
	year = {2022},
	author = {Dohlman, TH and McSoley, M and Amparo, F and Carreno-Galeano, T and M. Wang and Dastjerdi, M and Singh, RB and Coco, G and Di Zazzo, A and Shikari, H and Saboo, U and Sippel, K and Ciralsky, J and Yoo, SH and Sticca, M and Wakamatsu, TH and Murthy, S and Hamrah, P and Jurkunas, U and Ciolino, J. B. and Gomes, JAP and Perez, VL and Yin, J}
}
@article {1586165,
	title = {Advances in the Medical Management of Neurotrophic Keratitis},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {335-340},
	abstract = {Neurotrophic Keratitis (NK) is a degenerative disorder of the cornea characterized by decreased or absent sensory corneal innervation, corneal epitheliopathy and impaired healing.The clinical presentation of NK can range from persistent epithelial defects to corneal perforation and management is often both challenging and protracted. Historically, the management of NK has consisted of non-specific strategies to facilitate corneal epithelial healing such as lubrication, bandage contact lenses and tarsorrhaphy. Recent advances in the development of therapeutics for NK have provided new and efficacious targeted strategies for its management.In this article, we review recombinant human nerve growth factor (Cenegermin), currently approved for clinical use in the United States and Europe, as well as other promising therapeutic options that are in pre-clinical development such as thymosine β4, connexin43 inhibitors, and artificial extracellular matrix components.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1900282},
	author = {Dohlman, Thomas H and Singh, Rohan Bir and Dana, Reza}
}
@article {1549007,
	title = {Orbital disease in neuro-ophthalmology},
	journal = {Curr Opin Ophthalmol},
	volume = {31},
	number = {6},
	year = {2020},
	month = {2020 Nov},
	pages = {469-474},
	abstract = {PURPOSE OF REVIEW: Orbital disease represents a diverse spectrum of pathology and can result in a variety of neuro-ophthalmic manifestations. The aim of this review is to provide updates on recent advances in our understanding of orbital disease secondary to thyroid eye disease, myositis, IgG4-related disease, sarcoidosis, granulomatosis with polyangiitis and various tumours. RECENT FINDINGS: With regards to thyroid eye disease, there have been recent advances in the development of steroid-sparing therapies, new modalities for objectively monitoring disease activity and increased understanding of the role of environmental risk factors. There has been interest in characterizing the clinical course and underlying mechanism of optic nerve disease secondary to orbital disorders, which has led to advances in how we monitor for and prevent permanent vision loss. Increased knowledge of orbital tumour subtype histopathology and the development of novel classification systems has had prognostic value and aided medical decision-making. SUMMARY: Orbital disease occurs secondary to a wide variety of diseases and can lead to neuro-ophthalmic manifestations with significant morbidity. Advances in our understanding of different subtypes of orbital disease have improved our ability to treat these potentially debilitating conditions.},
	keywords = {Humans, Ophthalmology, Optic Nerve Diseases, Orbital Diseases, Prognosis, Systemic Vasculitis},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000699},
	author = {Dohlman, Jenny C and Cestari, Dean M and Freitag, Suzanne K}
}
@article {1677691,
	title = {Severe Eyelid Malformation With Facial Clefting and Amniotic Bands},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {4},
	year = {2023},
	month = {2023 Jul-Aug 01},
	pages = {e117-e119},
	abstract = {Amniotic bands can lead to eyelid colobomas contiguous with facial clefts, resulting in severe and highly variable eyelid malformations. There is no known underlying genetic cause of amniotic band sequence. Here, the authors review the case of an infant born with large, 4-eyelid colobomatous defects in the setting of facial clefts, amniotic bands and an underlying SMOC1 mutation, which has not previously been linked to amniotic band sequence or eyelid colobomas. Reconstructive technique and the postoperative course are described, and underlying etiologic theories of amniotic band sequence are reviewed and expanded upon. Although amblyopia prevention in this patient with poor visual potential was not a consideration, the goals of improving the patient{\textquoteright}s ocular surface and maintaining eye contact were achieved.},
	keywords = {Amniotic Band Syndrome, Coloboma, Eyelid Diseases, Eyelids, Humans, Infant, Infant, Newborn},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002374},
	author = {Dohlman, Jenny C and Elliott, Alexandra T}
}
@article {1439847,
	title = {Punctal agenesis: Embryology, presentation, management modalities and outcomes},
	journal = {Ann Anat},
	volume = {224},
	year = {2019},
	month = {2019 Jul},
	pages = {113-116},
	abstract = {Punctal agenesis is defined as the absence of the punctum occurring secondary to a failure of embryogenesis. This review synthesizes existing data on the embryology, anatomy, clinical presentation, symptomatology, management options and treatment outcomes of punctal agenesis. A foundational knowledge of the underlying embryologic and anatomical abnormalities is fundamental to understanding its clinical presentation and assists in choosing an appropriate management strategy. Existing outcomes data is generally favorable and suggests management with a step-wise approach can alleviate symptoms in patients across a spectrum of disease.},
	issn = {1618-0402},
	doi = {10.1016/j.aanat.2019.04.004},
	author = {Dohlman, Jenny C and Habib, Larissa A and Freitag, Suzanne K}
}
@article {1598072,
	title = {Clinical Reasoning: A 28-Year-Old Woman With Vision Loss and an Unusual Gait},
	journal = {Neurology},
	volume = {97},
	number = {18},
	year = {2021},
	month = {2021 Nov 02},
	pages = {e1860-e1865},
	issn = {1526-632X},
	doi = {10.1212/WNL.0000000000012446},
	author = {Dohlman, Jenny C and Chwalisz, Bart K and Stephen, Christopher D}
}
@article {1647908,
	title = {The Boston Keratoprosthesis-The First 50 Years: Some Reminiscences},
	journal = {Annu Rev Vis Sci},
	volume = {8},
	year = {2022},
	month = {2022 09 15},
	pages = {1-32},
	abstract = {Millions of people worldwide are bilaterally blind due to corneal diseases including infectious etiologies, trauma, and chemical injuries. While corneal transplantation can successfully restore sight in many, corneal graft survival decreases in eyes with chronic inflammation and corneal vascularization. Additionally, the availability of donor cornea material can be limited, especially in underdeveloped countries where corneal blindness may also be highly prevalent. Development of methods to create and implant an artificial cornea (keratoprosthesis) may be the only option for patients whose eye disease is not suitable for corneal transplantation or who live in regions where corneal transplantation is not possible. The Boston Keratoprosthesis (B-KPro) is the most commonly implanted keratoprosthesis worldwide, having restored vision in thousands of patients. This article describes the initial design of the B-KPro and the modifications that have been made over many years. Additionally, some of the complications of surgical implantation and long-term care challenges, particularly complicating inflammation and glaucoma, are discussed.},
	keywords = {Artificial Organs, Cornea, Corneal Diseases, Humans, Inflammation, Prostheses and Implants, Prosthesis Implantation, Treatment Outcome, Visual Acuity},
	issn = {2374-4650},
	doi = {10.1146/annurev-vision-100820-021253},
	author = {Dohlman, Claes}
}
@article {1504073,
	title = {Subperiosteal Masqueraders as Compared to Subperiosteal Abscess: Contrasting Clinical Presentation and Radiographic Densities},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {36},
	number = {6},
	year = {2020},
	month = {2020 Nov/Dec},
	pages = {596-600},
	abstract = {PURPOSE: Subperiosteal orbital lesions are most commonly abscesses secondary to sinusitis but, in rare cases, may represent other processes. Here, the authors compare the clinical and radiographic presentation of subperiosteal abscesses and alternate subperiosteal processes ("masqueraders") in an effort to establish distinguishing preoperative diagnostic criteria. METHODS: A retrospective chart review of cases of subperiosteal orbital lesions that underwent surgical intervention over a 3-year period was performed. The medical records of 6 cases of subperiosteal masqueraders and 6 cases of abscesses were reviewed for the clinical course, imaging (including radiographic density of lesions), and pathology. Clinical and radiographic features of the 2 groups were compared. RESULTS: All cases presented with orbital signs on exam. Fever and leukocytosis were absent in the masquerader group and present in 3 patients from the abscess group. Common radiographic findings in both groups included a rim-enhancing convex mass along the orbital wall and adjacent sinus opacification, often with bony dehiscence. Of the masqueraders, the final diagnosis was hematoma in 3 cases, mucocele in 1, and malignancy in 2. The difference between the mean radiodensity of the subperiosteal abscesses, 38 {\textpm} 5 Hounsfield units (95\% CI, 34-42), as compared with the average radiodensity of the masqueraders, 71 {\textpm} 5 Hounsfield units (95\% CI, 67-75), was significant (p = 0.042). Comparing radiodensity of the orbital lesion to adjacent sinus lesions and metastatic lesions elsewhere was also informative in establishing the diagnosis. CONCLUSIONS: Radiographic features, particularly radiodensity, may help distinguish subperiosteal abscesses from other lesions and aid in preoperative diagnosis and management.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001659},
	author = {Dohlman, Jenny C and Habib, Larissa A and Cunnane, Mary E and Yoon, Michael K}
}
@article {1559569,
	title = {Targeted steroid ointment application to the lid margins in ocular graft-versus-host disease associated blepharitis treatment},
	journal = {Ocul Surf},
	volume = {21},
	year = {2021},
	month = {2021 Jul},
	pages = {348-350},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.12.002},
	author = {Domenech-Estarellas, Edgar A and Mamata, Hikari and Luo, Zhonghui Katie}
}
@article {1647871,
	title = {Idelalisib inhibits experimental proliferative vitroretinopathy},
	journal = {Lab Invest},
	volume = {102},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {1296-1303},
	abstract = {Proliferative vitreoretinopathy (PVR) is a fibrotic eye disease that develops after rhegmatogenous retinal detachment surgery and open-globe traumatic injury. Idelalisib is a specific inhibitor of phosphoinositide 3-kinase (PI3K) δ. While PI3Kδ is primarily expressed in leukocytes, its expression is also considerably high in retinal pigment epithelial (RPE) cells, which play a crucial part in the PVR pathogenesis. Herein we show that GeoMx Digital Spatial Profiling uncovered strong expression of fibronectin in RPE cells within epiretinal membranes from patients with PVR, and that idelalisib (10 μM) inhibited Akt activation, fibronectin expression and collagen gel contraction induced by transforming growth factor (TGF)-β2 in human RPE cells. Furthermore, we discovered that idelalisib at a vitreal concentration of 10 μM, a non-toxic dose to the retina, prevented experimental PVR induced by intravitreally injected RPE cells in rabbits assessed by experienced ophthalmologists using an indirect ophthalmoscope plus a + 30 D fundus lens, electroretinography, optical coherence tomography and histological analysis. These data suggested idelalisib could be harnessed for preventing patients from PVR.},
	keywords = {Animals, Fibronectins, Humans, Phosphatidylinositol 3-Kinases, Quinazolinones, Rabbits, Retinal Pigment Epithelium, Vitreoretinopathy, Proliferative},
	issn = {1530-0307},
	doi = {10.1038/s41374-022-00822-7},
	author = {Dong, Lijun and Han, Haote and Huang, Xionggao and Ma, Gaoen and Fang, Dong and Qi, Hui and Han, Zhuo and Wang, Luping and Tian, Jingkui and Vanhaesebroeck, Bart and Zhang, Guoming and Zhang, Shaochong and Lei, Hetian}
}
@article {694761,
	title = {An open-source computational tool to automatically quantify immunolabeled retinal ganglion cells.},
	journal = {Exp Eye Res},
	volume = {147},
	year = {2016},
	month = {2016 Jun},
	pages = {50-6},
	abstract = {A fully automated and robust method was developed to quantify β-III-tubulin-stained retinal ganglion cells, combining computational recognition of individual cells by CellProfiler and a machine-learning tool to teach phenotypic classification of the retinal ganglion cells by CellProfiler Analyst. In animal models of glaucoma, quantification of immunolabeled retinal ganglion cells is currently performed manually and remains time-consuming. Using this automated method, quantifications of retinal ganglion cell images were accelerated tenfold: 1800 images were counted in 3\&nbsp;h using our automated method, while manual counting of the same images took 72\&nbsp;h. This new method was validated in an established murine model of microbead-induced optic neuropathy. The use of the publicly available software and the method{\textquoteright}s user-friendly design allows this technique to be easily implemented in any laboratory.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2016.04.012},
	author = {Dordea, Ana C and Bray, Mark-Anthony and Allen, Kaitlin and Logan, David J and Fei, Fei and Malhotra, Rajeev and Gregory, Meredith S and Carpenter, Anne E and Buys, Emmanuel S}
}
@article {1363272,
	title = {Peri-saccadic natural vision},
	journal = {J Neurosci},
	volume = {33},
	number = {3},
	year = {2013},
	month = {2013 Jan 16},
	pages = {1211-7},
	abstract = {The fundamental role of the visual system is to guide behavior in natural environments. To optimize information transmission, many animals have evolved a non-homogeneous retina and serially sample visual scenes by saccadic eye movements. Such eye movements, however, introduce high-speed retinal motion and decouple external and internal reference frames. Until now, these processes have only been studied with unnatural stimuli, eye movement behavior, and tasks. These experiments confound retinotopic and geotopic coordinate systems and may probe a non-representative functional range. Here we develop a real-time, gaze-contingent display with precise spatiotemporal control over high-definition natural movies. In an active condition, human observers freely watched nature documentaries and indicated the location of periodic narrow-band contrast increments relative to their gaze position. In a passive condition under central fixation, the same retinal input was replayed to each observer by updating the video{\textquoteright}s screen position. Comparison of visual sensitivity between conditions revealed three mechanisms that the visual system has adapted to compensate for peri-saccadic vision changes. Under natural conditions we show that reduced visual sensitivity during eye movements can be explained simply by the high retinal speed during a saccade without recourse to an extra-retinal mechanism of active suppression; we give evidence for enhanced sensitivity immediately after an eye movement indicative of visual receptive fields remapping in anticipation of forthcoming spatial structure; and we demonstrate that perceptual decisions can be made in world rather than retinal coordinates.},
	keywords = {Adult, Eye Movement Measurements, Eye Movements, Humans, Male, Middle Aged, Photic Stimulation, Saccades, Vision, Binocular, Visual Fields},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.4344-12.2013},
	author = {Dorr, Michael and Bex, Peter J}
}
@article {1452949,
	title = {Binocular Summation and Suppression of Contrast Sensitivity in Strabismus, Fusion and Amblyopia},
	journal = {Front Hum Neurosci},
	volume = {13},
	year = {2019},
	month = {2019},
	pages = {234},
	abstract = {: Amblyopia and strabismus affect 2\%-5\% of the population and cause a broad range of visual deficits. The response to treatment is generally assessed using visual acuity, which is an insensitive measure of visual function and may, therefore, underestimate binocular vision gains in these patients. On the other hand, the contrast sensitivity function (CSF) generally takes longer to assess than visual acuity, but it is better correlated with improvement in a range of visual tasks and, notably, with improvements in binocular vision. The present study aims to assess monocular and binocular CSFs in amblyopia and strabismus patients. : Both monocular CSFs and the binocular CSF were assessed for subjects with amblyopia ( = 11), strabismus without amblyopia ( = 20), and normally sighted controls ( = 24) using a tablet-based implementation of the quick CSF, which can assess a full CSF in \&lt;3 min. Binocular summation was evaluated against a baseline model of simple probability summation. : The CSF of amblyopic eyes was impaired at mid-to-high spatial frequencies compared to fellow eyes, strabismic eyes without amblyopia, and control eyes. Binocular contrast summation exceeded probability summation in controls, but not in subjects with amblyopia (with or without strabismus) or strabismus without amblyopia who were able to fuse at the test distance. Binocular summation was less than probability summation in strabismic subjects who were unable to fuse. : We conclude that monocular and binocular contrast sensitivity deficits define important characteristics of amblyopia and strabismus that are not captured by visual acuity alone and can be measured efficiently using the quick CSF.},
	issn = {1662-5161},
	doi = {10.3389/fnhum.2019.00234},
	author = {Dorr, Michael and Kwon, MiYoung and Lesmes, Luis Andres and Miller, Alexandra and Kazlas, Melanie and Chan, Kimberley and Hunter, David G and Lu, Zhong-Lin and Bex, Peter J}
}
@article {1363271,
	title = {Rapid and reliable assessment of the contrast sensitivity function on an iPad},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {12},
	year = {2013},
	month = {2013 Nov 05},
	pages = {7266-73},
	abstract = {PURPOSE: Letter acuity, the predominant clinical assessment of vision, is relatively insensitive to slow vision loss caused by eye disease. While the contrast sensitivity function (CSF) has demonstrated the potential to monitor the slow progress of blinding eye diseases, current tests of CSF lack the reliability or ease-of-use to capture changes in vision timely. To improve the current state of home testing for vision, we have developed and validated a computerized adaptive test on a commercial tablet device (iPad) that provides an efficient and easy-to-use assessment of the CSF. METHODS: We evaluated the reliability, accuracy, and flexibility of tablet-based CSF assessment. Repeated tablet-based assessments of the spatial CSF, obtained from four normally-sighted observers, which each took 3 to 5 minutes, were compared to measures obtained on CRT-based laboratory equipment; additional tablet-based measures were obtained from six subjects under three different luminance conditions. RESULTS: A Bland-Altman analysis demonstrated that tablet-based assessment was reliable for estimating sensitivities at specific spatial frequencies (coefficient of repeatability 0.14-0.40 log units). The CRT- and tablet-based results demonstrated excellent agreement with absolute mean sensitivity differences \&lt;0.05 log units. The tablet-based test also reliably identified changes in contrast sensitivity due to different luminance conditions. CONCLUSIONS: We demonstrate that CSF assessment on a mobile device is indistinguishable from that obtained with specialized laboratory equipment. We also demonstrate better reliability than tests used currently for clinical trials of ophthalmic therapies, drugs, and devices.},
	keywords = {Adult, Computers, Handheld, Contrast Sensitivity, Diagnosis, Computer-Assisted, Female, Humans, Male, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Vision Disorders, Vision Tests, Young Adult},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-11743},
	author = {Dorr, Michael and Lesmes, Luis A and Lu, Zhong-Lin and Bex, Peter J}
}
@article {1608587,
	title = {Unsupervised Machine Learning Identifies Quantifiable Patterns of Visual Field Loss in Idiopathic Intracranial Hypertension},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {9},
	year = {2021},
	month = {2021 Aug 02},
	pages = {37},
	abstract = {Purpose: Archetypal analysis, a form of unsupervised machine learning, identifies archetypal patterns within a visual field (VF) dataset such that any VF is described as a weighted sum of its archetypes (ATs) and has been used to quantify VF defects in glaucoma. We applied archetypal analysis to VFs affected by nonglaucomatous optic neuropathy caused by idiopathic intracranial hypertension (IIH). Methods: We created an AT model from 2862 VFs prospectively collected from 330 eyes in the IIH Treatment Trial (IIHTT). We compared baseline IIH AT patterns with their descriptive VF classifications from the IIHTT. Results: The optimum IIH AT model yielded 14 ATs resembling VF patterns reported in the IIHTT. Baseline VFs contained four or fewer meaningful ATs in 147 (89\%) of study eyes. AT2 (mild general VF depression pattern) demonstrated the greatest number of study eyes with meaningful AT weight at baseline (n = 114), followed by AT1 (n = 91). Other ATs captured patterns of blind spot enlargement, hemianopia, arcuate, nasal defects, and more nonspecific patterns of general VF depression. Of all ATs, AT1 (normal pattern) had the strongest correlation with mean deviation (r = 0.69, P \&lt; 0.001). For 65 of the 93 VFs with a dominant AT, this AT matched the expert classification. Conclusions: Archetypal analysis identifies quantifiable, archetypal VF defects that resemble those commonly seen in IIH. Translational Relevance: Archetypal analysis provides a quantitative, objective method of measuring and monitoring disease-specific regional VF defects in IIH.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.9.37},
	author = {Doshi, Hiten and Solli, Elena and Tobias Elze and Pasquale, Louis R and Wall, Michael and Kupersmith, Mark J}
}
@article {1638567,
	title = {Unsupervised Machine Learning Shows Change in Visual Field Loss in the Idiopathic Intracranial Hypertension Treatment Trial},
	journal = {Ophthalmology},
	year = {2022},
	month = {2022 Apr 01},
	abstract = {PURPOSE: We previously reported that archetypal analysis (AA), a type of unsupervised machine learning, identified and quantified patterns of visual field (VF) loss in idiopathic intracranial hypertension (IIH), referred to as archetypes (ATs). We assessed whether AT weight changes over time are consistent with changes in conventional global indices. We explored whether visual outcome or treatment effects are associated with select ATs and whether AA reveals residual VF defects in eyes deemed "normal" after treatment. DESIGN: Analysis of data collected from a randomized controlled trial. PARTICIPANTS: 2,862 VFs taken from 165 participants during the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: We applied a 14-AT model derived from IIHTT VFs. We examined changes in individual AT weights over time within all study eye VFs and evaluated differences between treatment groups. We created an AT Change score to assess overall VF change from baseline. We tested threshold baseline AT weights for association with VF outcome and treatment effect at six months. We determined the abnormal ATs with meaningful weight at outcome for VFs considered "normal" based on a mean deviation (MD) cutoff >=-2.00 dB. MAIN OUTCOME MEASURES: Individual AT weighting coefficients, MD. RESULTS: AT1 (a normal VF pattern) showed the greatest weight change for all study eyes, increasing from 11.9\% (interquartile range [IQR]: 0.44-24.1\%) at baseline to 31.2\% (IQR: 16.0-45.5\%) at outcome (p\&lt;0.001). AT1 weight change (r=0.795, p\&lt;0.001) and a global score of AT change (r=0.988, p\&lt;0.001) correlated strongly with MD change. Study eyes with baseline AT2 (a mild diffuse VF loss pattern) weight >= 44\% (>=1 standard deviation above the mean) showed higher AT2 weights at outcome than those with AT2 \&lt; 44\% at baseline (p\&lt;0.001). Only the latter group showed a significant acetazolamide treatment effect. AA revealed residual VF loss patterns, most frequently representing mild diffuse loss and enlarged blind spot in 64 of 66 study eyes with MD >=-2.00 dB at outcome. CONCLUSION: AA provides a quantitative approach to monitoring VF changes in IIH. Baseline AT features may be associated with treatment response and VF outcome. AA uncovers residual VF defects not otherwise revealed by MD.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.03.027},
	author = {Doshi, Hiten and Solli, Elena and Tobias Elze and Pasquale, Louis R and Wall, Michael and Kupersmith, Mark J}
}
@article {1538334,
	title = {Hemorrhagic Papilledema Secondary to Craniopharyngioma},
	journal = {JAMA Ophthalmol},
	volume = {138},
	number = {10},
	year = {2020},
	month = {2020 Oct 01},
	pages = {e200880},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.0880},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Chwalisz, Bart K}
}
@article {1580510,
	title = {Ptosis as Clinical Presentation in a Patient With Emery-Dreifuss Muscular Dystrophy Type 5},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {3},
	year = {2021},
	month = {2021 Sep 01},
	pages = {e333-e334},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001187},
	author = {Douglas, Konstantinos Aa and Douglas, Vivian Paraskevi and Gaier, Eric D and Chwalisz, Bart K}
}
@article {1623344,
	title = {Oculomotor nerve schwannoma: case series and literature review},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {4},
	year = {2022},
	month = {2022 Jul-Aug},
	pages = {1160-1174},
	abstract = {Oculomotor nerve schwannomas are rare benign cranial nerve tumors. There are only a limited number of reports on this pathology in the literature, and there are currently no established management guidelines that aid providers in deciding on surgical versus nonsurgical management. We assess the published literature on the topic to identify indications for treatment as well as outcome measures (e.g., local control rates, survival rates, and complication rates) that have been reported as associated with the various treatment modalities. We attempt to develop an algorithm for evaluation and treatment of oculomotor nerve schwannomas in order to establish consensus on how these tumors should be treated.},
	keywords = {Algorithms, Cranial Nerve Neoplasms, Humans, Neurilemmoma, Oculomotor Nerve, Oculomotor Nerve Diseases},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2021.11.008},
	author = {Douglas, Vivian Paraskevi and Flores, Christopher and Douglas, Konstantinos Aa and Strominger, Mitchell B and Kasper, Ekkehard and Torun, Nurhan}
}
@article {1638552,
	title = {McArdle Disease Rhabdomyolysis Precipitated by Acetazolamide for Idiopathic Intracranial Hypertension},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {4},
	year = {2023},
	month = {2023 Dec 01},
	pages = {e159-e160},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001568},
	author = {Douglas, Vivian Paraskevi and Owji, Shahin and Pakravan, Mohammad and Charoenkijkajorn, Chaow and Lee, Andrew G}
}
@article {1474222,
	title = {Relapsing Optic Neuropathy and Multiple Cranial Neuropathies in a Middle-Aged Woman},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Nov 07},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.4410},
	author = {Douglas, Konstantinos Aa and Douglas, Vivian Paraskevi and Cestari, Dean M}
}
@article {1638565,
	title = {Subthreshold Exudative Choroidal Neovascularization (CNV): Presentation of This Uncommon Subtype and Other CNVs in Age-Related Macular Degeneration (AMD)},
	journal = {J Clin Med},
	volume = {11},
	number = {8},
	year = {2022},
	month = {2022 Apr 07},
	abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in people over the age of 50 worldwide. Exudative or neovascular AMD is a more severe subset of AMD which is characterized by the presence of choroidal neovascularization (CNV). Recent advancements in multimodal ophthalmic imaging, including optical coherence tomography (OCT) and OCT-angiography (OCT-A), have facilitated the detection and characterization of previously undetectable neovascular lesions and have enabled a more refined classification of CNV in exudative as well as nonexudative AMD patients. Subthreshold exudative CNV is a novel subtype of exudative AMD that typically presents asymptomatically with good visual acuity and is characterized by stable persistent or intermittent subretinal fluid (SRF). This review aims to provide an overview of the clinical as well as multimodal imaging characteristics of CNV in AMD, including this new clinical phenotype, and propose effective approaches for management.},
	issn = {2077-0383},
	doi = {10.3390/jcm11082083},
	author = {Douglas, Vivian Paraskevi and Garg, Itika and Douglas, Konstantinos Aa and Miller, John B}
}
@article {1615212,
	title = {Ophthalmic manifestations of dementing disorders},
	journal = {Curr Opin Ophthalmol},
	volume = {32},
	number = {6},
	year = {2021},
	month = {2021 Nov 01},
	pages = {515-520},
	abstract = {PURPOSE OF REVIEW: Dementia is a term for loss of memory, language, problem-solving, and other thinking abilities, which significantly interferes with daily life. Certain dementing conditions may also affect visual function. The eye is an accessible window to the brain that can provide valuable information for the early diagnosis of people who suffer from Alzheimer{\textquoteright}s disease, Parkinson{\textquoteright}s disease, dementia with Lewy bodies as well as from more rare causes of dementias, such as Creutzfeldt-Jacob and Huntington{\textquoteright}s diseases. Herein, we present the ocular manifestations of neurocognitive disorders focusing on the neuro-ophthalmic ones and further discuss potential ocular biomarkers that could help in early detection of these disorders. RECENT FINDINGS: Ophthalmic examination along with the recent developments in in-vivo testing have provided a strong foundation of useful knowledge about brain disorder in neurodegenerative diseases without the need for invasive studies. Currently, a number of visual measures, such as visual acuity, contrast sensitivity, pupil response, and saccades in addition to various ophthalmic tests, such as electroretinogram, visual evoked potential, optical coherence tomography (OCT), and OCT-angiography have been widely used and evaluated as potential biomarkers for different stages of dementia. SUMMARY: Ophthalmologic and neuro-ophthalmic evaluation is evolving as an important part of the early diagnosis and management of people with dementia. A particular focus on ocular biomarkers in dementing illnesses has arisen over the past few years and there are several promising measures and imaging tools that have been proposed as potential biomarkers for these diseases.},
	keywords = {Alzheimer Disease, Brain, Evoked Potentials, Visual, Humans, Huntington Disease, Parkinson Disease},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000807},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Cestari, Dean M}
}
@article {1638562,
	title = {Short- and Long-Term Visual Outcomes in Patients Receiving Intravitreal Injections: The Impact of the Coronavirus 2019 Disease (COVID-19)-Related Lockdown},
	journal = {J Clin Med},
	volume = {11},
	number = {8},
	year = {2022},
	month = {2022 Apr 08},
	abstract = {Purpose: To investigate the short- and long-term impact of COVID-19-related lockdown on the vision of patients requiring intravitreal injections (IVI) for neovascular Age-related Macular degeneration (nvAMD), diabetic retinopathy (DR), central retinal vein occlusion (CRVO), or branch retinal vein occlusion (BRVO). Methods: This is a retrospective study from the Retina department of three Mass Eye and Ear centers. Charts of patients age of >= 18 years with any of the abovementioned diagnoses who had a scheduled appointment anytime between 17 March 2020 until 18 May 2020 (lockdown period in Boston, Massachusetts) were reviewed at baseline (up to 12 weeks before the lockdown), at first available follow-up (=actual f/u) during or after the lockdown period, at 3 months, 6 months, and at last available completed appointment of 2020. Results: A total of 1001 patients met the inclusion criteria. Of those patients, 479 (47.9\%) completed their intended f/u appointment, while 522 missed it (canceled and "no show"). The delay in care of those who missed it was 59.15 days [standard deviation (SD) {\textpm} 49.6]. In these patients, significant loss of vision was noted at actual f/u [Best corrected visual acuity (BCVA) in LogMAR (Logarithm of the Minimum Angle of Resolution)-mean ({\textpm}SD)-completed: 0.45 ({\textpm}0.46), missed: 0.53 ({\textpm}0.55); p = 0.01], which was more prominent in the DR group [Visual acuity (VA) change in LogMAR-mean ({\textpm}SD); completed: 0.04 ({\textpm}0.28), missed: 0.18 ({\textpm}0.44); p = 0.02] and CRVO [completed: -0.06 ({\textpm}0.27), missed: 0.11 ({\textpm}0.35); p = \&amp;lt;0.001] groups followed by nvAMD [completed: 0.006 ({\textpm}0.16), missed: 0.06 ({\textpm}0.27); p = 0.004] and BRVO [completed: -0.02 ({\textpm}0.1), missed: 0.03 ({\textpm}0.14); p = 0.02] ones. Overall, a higher percent of people who missed their intended f/u experienced vision loss of more than 15 letters at last f/u compared to those who completed it [missed vs. completed; 13.4\% vs. 7.4\% in nvAMD (p = 0.72), 7.8\% vs. 6.3\% in DR (0.84), 15.5\% vs. 9.9\% in CRVO (p \&amp;lt; 0.001) and 9.6\% vs. 2\% in BRVO (p = 0.48)]. Conclusions: Delay in care of about 8.45 weeks can lead to loss of vision in patients who receive IVI with DR and CRVO patients being more vulnerable in the short-term, whereas in the long-term, CRVO patients followed by the nvAMD patients demonstrating the least vision recovery. BRVO patients were less likely to be affected by the delay in care. Adherence to treatment is key for maintaining and improving visual outcomes in patients who require IVI.},
	issn = {2077-0383},
	doi = {10.3390/jcm11082097},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Vavvas, Demetrios G and Miller, Joan W and Miller, John B}
}
@article {1589743,
	title = {Case 292},
	journal = {Radiology},
	volume = {299},
	number = {1},
	year = {2021},
	month = {2021 Apr},
	pages = {234-236},
	abstract = {History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed (Figs 1, 2).},
	issn = {1527-1315},
	doi = {10.1148/radiol.2021201712},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Reinshagen, Katherine L and Chwalisz, Bart K}
}
@article {1470977,
	title = {Fulminant Pseudotumor Cerebri Syndrome Secondary to Over-the-Counter Topical Retinoids},
	journal = {J Neuroophthalmol},
	volume = {40},
	number = {2},
	year = {2020},
	month = {2020 Jun},
	pages = {248-249},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000857},
	author = {Douglas, Konstantinos Aa and Douglas, Vivian P and Chwalisz, Bart K}
}
@article {1452951,
	title = {Case report: Orbital myositis triggering oxygen-responsive cluster headache},
	journal = {Cephalalgia},
	volume = {40},
	number = {3},
	year = {2020},
	month = {2020 03},
	pages = {313-316},
	abstract = {BACKGROUND: Orbital myositis is an idiopathic, non-infectious condition, typically seen in young females and usually affecting one extraocular muscle. Orbital myositis mimicking cluster headache is a rare clinical entity, and this is the first description of a case of a secondary trigeminal autonomic cephalalgia from orbital myositis responsive to high-flow oxygen. CASE: A young woman presented with new-onset, oxygen-responsive headache, periorbital pain and autonomic features. She had associated vertical diplopia on downgaze and subtle ocular misalignment. An initial diagnosis of cluster headache was made. Initial brain MRI was unrevealing, but dedicated MRI of the orbits showed enhancement of orbital muscles. The diplopia and the imaging findings were consistent with orbital myositis. CONCLUSION: Orbital myositis mimicking cluster headache is rare, and not previously reported as an oxygen-responsive headache.},
	issn = {1468-2982},
	doi = {10.1177/0333102419865974},
	author = {Douglas, Vivian P and Douglas, Konstantinos Aa and Rizzo, Joseph F and Chwalisz, Bart K}
}
@article {1608591,
	title = {Case 292: Lyme Neuroborreliosis},
	journal = {Radiology},
	volume = {300},
	number = {2},
	year = {2021},
	month = {2021 Aug},
	pages = {484-488},
	abstract = {History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed.},
	issn = {1527-1315},
	doi = {10.1148/radiol.2021201715},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Reinshagen, Katherine L and Chwalisz, Bart K}
}
@article {1460355,
	title = {Immune checkpoint inhibitors: what neuro-ophthalmologists need to know},
	journal = {Curr Opin Ophthalmol},
	volume = {30},
	number = {6},
	year = {2019},
	month = {2019 Nov},
	pages = {426-433},
	abstract = {PURPOSE OF REVIEW: Immune checkpoint inhibitors are currently an exceedingly powerful tool in the management of hitherto incurable malignancies and their use in clinical practice is expected to increase in the near future. The purpose of this review is to discuss the current medical uses of checkpoint inhibitors with a focus on their neuro-ophthalmic side-effects. RECENT FINDINGS: Immune checkpoint inhibitors have emerged as a promising breakthrough in the treatment of several tumor types. However, these targeted therapies can induce a wide range of immune-related ophthalmic and neuro-ophthalmic toxicities. It is important for neuro-ophthamologists to promptly recognize and manage these adverse events that can potentially threaten vision. SUMMARY: There are currently seven FDA-approved immune checkpoint inhibitors and several ones are under investigation. In general, immunotherapy is considered a well tolerated, safe and efficacious treatment option for many cancer patients. Nevertheless, because of their unique mechanism of action, these molecules can alter the immune response and result in immune-related adverse effects in almost every organ with an estimated incidence of ophthalmic side effects in this patient population of less than 1\%.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000608},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Cestari, Dean M}
}
@article {1517170,
	title = {Ocular Manifestations of COVID-19 (SARS-CoV-2): A Critical Review of Current Literature},
	journal = {In Vivo},
	volume = {34},
	number = {3 Suppl},
	year = {2020},
	month = {2020 Jun},
	pages = {1619-1628},
	abstract = {The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.},
	keywords = {Abducens Nerve Diseases, Antiviral Agents, Betacoronavirus, Biomarkers, China, Conjunctival Diseases, Contact Lenses, Coronavirus Infections, Equipment Contamination, Eye Diseases, Humans, Hyperemia, Immunization, Passive, Infectious Disease Transmission, Patient-to-Professional, Keratoconjunctivitis, Lacrimal Apparatus Diseases, Leukocyte Count, Pandemics, Pneumonia, Viral, Retinal Diseases, Retrospective Studies},
	issn = {1791-7549},
	doi = {10.21873/invivo.11952},
	author = {Douglas, Konstantinos Aa and Douglas, Vivian Paraskevi and Moschos, Marilita M}
}
@article {1798451,
	title = {The epidemiology of pediatric dry eye disease in the United States: An IRIS{\textregistered} registry (Intelligent Research in Sight) analysis},
	journal = {Ocul Surf},
	volume = {32},
	year = {2024},
	month = {2024 Jan 28},
	pages = {106-111},
	abstract = {PURPOSE: Dry-eye disease (DED) is a chronic progressive ocular surface disorder with limited studies in the pediatric population. The Academy of Ophthalmology{\textquoteright}s IRIS{\textregistered} Registry was leveraged to investigate the prevalence of DED in the pediatric population (PDED, patients \&lt;18 years old) and the demographic differences of DED between pediatric and adult patients (ADED).

METHODS: Retrospective cohort study. Patients with DED between January 1st, 2013 and December 31st, 2019 (N~=~4,795,979) were included. Descriptive statistics, Pearson{\textquoteright}s chi-squared tests and two-sample proportions tests were conducted to compare key demographic distributions between the ADED and PDED cohorts.

RESULTS: The average age at onset for ADED patients was 61.06 ({\textpm}14.75) years and for PDED patients was 12.51 ({\textpm}3.86). The overall tests for independence and the individual tests of proportions of each category were statistically significant for all demographic characteristics (p~\&lt;~0.001). Characteristics with the largest discrepancies between patients of PDED and the IRIS Registry pediatric patient pool (PIRIS) included female sex (58.08~\% vs. 50.60~\%), male sex (41.58~\% vs. 48.78~\%) and Asian race (6.02~\% vs. 3.11~\%) respectively. Within the PDED cohort, females were at higher risk of PDED (58~\% vs. 42~\%). PDED was more prevalent in children with refractive errors (76~\%) and eyelid/conjunctival disorders (41~\%). Characteristics with the largest discrepancies between PDED and ADED patients included female sex (58.08 \% vs. 68.12~\%), male sex (41.58 \% vs. 31.55~\%) and Caucasian race (50.24 \% vs. 67.06 \%) respectively.

CONCLUSIONS: Significant differences in the PDED cohort are demonstrated in this study. PDED was more prevalent in the female sex and Caucasian race compared to PIRIS and was more commonly associated with refractive errors and eyelid/conjunctival disorders.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2024.01.012},
	author = {Douglas, Vivian Paraskevi and Hall, Nathan and Ross, Connor and Douglas, Konstantinos Aa and Tobias Elze and Miller, Joan W and Lorch, Alice C and Traish, Aisha S}
}
@article {1460352,
	title = {Neuro-ophthalmic manifestations of the phakomatoses},
	journal = {Curr Opin Ophthalmol},
	volume = {30},
	number = {6},
	year = {2019},
	month = {2019 Nov},
	pages = {434-442},
	abstract = {PURPOSE OF REVIEW: The phakomatoses are a group of inherited disorders with variable clinical manifestations that are characterized by brain, cutaneous, ocular and other distinct lesions in multiple organs. Correctly recognizing the neuro-ophthalmic signs and symptoms can lead to early diagnosis and treatment. The group is composed of neurofibromatosis (type 1 and 2), tuberous sclerosis complex, von Hippel-Lindau, ataxia-telangiectasia and Sturge-Weber syndromes. However, more than 60 syndromes have been described in the medical literature. This review provides an update on the diagnosis and management of phakomatoses with a focus on their clinical neuro-ophthalmic manifestations. RECENT FINDINGS: Phakomatoses are a group of inherited syndromes with variable clinical manifestations that are characterized by brain, cutaneous, ocular and other distinct lesions in multiple organs. Recent advances in diagnostic and treatment options that have contributed to prompt recognition and management of these disorders are discussed with an emphasis on the beneficial effects on vision. SUMMARY: Phakomatoses, also known as neuro-oculo-cutaneous syndromes, are inherited disorders with characteristic lesions in multiple organs. Because of their frequent ocular involvement thorough ophthalmologic and neuro-ophthalmic evaluation is critical in this patient population in order to prevent vision loss and life-threatening complications that are often associated with these disorders.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000609},
	author = {Douglas, Konstantinos Aa and Douglas, Vivian Paraskevi and Cestari, Dean M}
}
@article {1549008,
	title = {Optic nerve sheath meningioma},
	journal = {Curr Opin Ophthalmol},
	volume = {31},
	number = {6},
	year = {2020},
	month = {2020 Nov},
	pages = {455-461},
	abstract = {PURPOSE OF REVIEW: Optic nerve sheath meningiomas (ONSMs) are rare benign tumors of the anterior visual pathway which present with slowly progressive and painless vision loss and account for approximately 2\% of all orbital tumors. This article provides an overview as well as an update on the ONSMs with regards to cause, epidemiology, clinical presentation, diagnosis, and management in adults and pediatric population. RECENT FINDINGS: The clinical presentation and prognosis of ONSMs can vary and largely depend on the location of tumor as well as the histologic type. Overall, the diagnosis is based on clinical presentation, examination, and neuroimaging findings. Nevertheless, delays in diagnosis or misdiagnosis are not uncommon and can result in higher morbidity rates. Recent advances in diagnostic as well as more effective and less-invasive treatment options are discussed in this review. SUMMARY: ONSMs are a rare cause of slowly progressive and inexorable visual loss. Although ONSM diagnosis depends on the characteristic clinical and radiologic findings, prompt diagnosis, and appropriate management is critical for favorable visual outcomes. Thus, current focus is optimizing diagnostic as well-treatment methods for patients with ONSMs.},
	keywords = {Humans, Meningioma, Neuroimaging, Optic Nerve Neoplasms, Prognosis, Vision Disorders},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000700},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Cestari, Dean M}
}
@article {1586160,
	title = {Nelson Syndrome: Clival Invasion of Corticotroph Pituitary Adenoma Resulting in Alternating Sixth Nerve Palsies},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {1},
	year = {2021},
	month = {2021 Mar 01},
	pages = {114-118},
	abstract = {ABSTRACT: A 44-year-old woman presented with 2 painful and self-limited episodes of binocular horizontal diplopia within 1 year that at the beginning were thought to be secondary to microvascular insult. Her medical history was significant for Cushing syndrome status post transsphenoidal resection with bilateral adrenalectomy 4 years prior, hypertension, and diabetes mellitus. Neuro-ophthalmic evaluation was significant for left abduction deficit and incomitant esotropia consistent with left abducens nerve palsy. Of note, the patient had experienced a similar episode but on the contralateral side a few months prior. Although initially MRI of the brain demonstrated stable residual postoperative finding in the sella, upon review, an heterogenous T-1 hypointense marrow in the clivus was noted. Hypermetabolism of the clivus was also noted on computed tomography positron emission tomography of the skull base. A clival biopsy demonstrated a corticotroph adenoma with elevated proliferation index and scattered mitoses. A corticotroph pituitary adenoma after adrenalectomy, also known as Nelson syndrome, was diagnosed. Radiation therapy was offered to the patient, and resolution of symptoms was gradually observed.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001141},
	author = {Douglas, Vivian P and Douglas, Konstantinos Aa and Rapalino, Otto and Champion, Samantha N and Chwalisz, Bart K}
}
@article {1598050,
	title = {Absent Foveal Avascular Zone in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {2},
	year = {2021},
	month = {2021 Jun 01},
	pages = {e166-e168},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001050},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Miller, John B and Gaier, Eric D}
}
@article {1688276,
	title = {Optical coherence tomography angiography in neuro-ophthalmology},
	journal = {Curr Opin Ophthalmol},
	volume = {34},
	number = {4},
	year = {2023},
	month = {2023 Jul 01},
	pages = {354-360},
	abstract = {PURPOSE OF REVIEW: Optical coherence tomography angiography (OCTA) is a novel, noninvasive imaging technique, which provides depth resolved visualization of microvasculature of the retina and choroid. Although OCTA has been widely used for the evaluation of a number of retinal diseases, its use in the field of neuro-ophthalmology has been less studied. In this review, we provide an update on the utility of OCTA in neuro-ophthalmic conditions. RECENT FINDINGS: Peripapillary and macular microvasculature analyses have indicated that OCTA can be a promising tool for early detection of a number of neuro-ophthalmic diseases, differential diagnosis, and monitoring of disease progression. Recent studies have demonstrated that structural and functional impairment can develop at early stages in some conditions such as in multiple sclerosis and Alzheimer{\textquoteright}s disease even in the absence of overt clinical symptoms. Furthermore, this dye-less technique can be a valuable adjunct tool in the detection of complications commonly seen in some congenital entities such optic disc drusen. SUMMARY: Since its introduction, OCTA has emerged as an important imaging approach shedding light on unrevealed pathophysiological mechanisms of several ocular diseases. The use of OCTA as a biomarker in the field of neuro-ophthalmology has recently gained considerable attention with studies supporting its role in clinical setting while larger studies are warranted for correlating these findings with traditional diagnostic procedures and clinical features and outcomes.},
	keywords = {Angiography, Fluorescein Angiography, Humans, Ophthalmology, Retina, Retinal Diseases, Retinal Vessels, Tomography, Optical Coherence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000955},
	author = {Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Torun, Nurhan}
}
@article {1814341,
	title = {Understanding viewpoint changes in peripheral prisms for field expansion by virtual reality simulation},
	journal = {Biomed Opt Express},
	volume = {15},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {1393-1407},
	abstract = {Prism field expansion is a common treatment for patients with peripheral field loss, shifting images from the blind field into the seeing field. The shifted image originates from a new viewpoint translated and rotated from the original viewpoint by the prism. To understand such viewpoint changes, we simulated two field expansion methods in virtual reality: 1) angular (i.e., rotational) field expansion and 2) linear field expansion via image crop-and-shift. Changes to object locations, sizes, and optic flow patterns by those methods were demonstrated and analyzed in both static and dynamic conditions, which may affect navigation with such field expansion devices.},
	issn = {2156-7085},
	doi = {10.1364/BOE.513758},
	author = {Doyon, Jonathan K and Hwang, Alex D and Jung, Jae-Hyun}
}
@article {1445331,
	title = {Survey of practice patterns for the management of ophthalmic genetic disorders among AAPOS members: report by the AAPOS Genetic Eye Disease Task Force},
	journal = {J AAPOS},
	year = {2019},
	month = {2019 Jun 21},
	abstract = {To better understand AAPOS member pediatric ophthalmologists{\textquoteright} knowledge and needs regarding genetic eye disorders, the AAPOS Genetic Eye Disease Task Force developed a 16-question survey that was circulated to national and international AAPOS members. Responses to questions on practice patterns, baseline knowledge, and educational interests regarding patients with suspected ophthalmic genetic disorders were collected. A majority of respondents (93\%) evaluate patients with suspected genetic disorders. Knowledge gaps were present in heritability of certain conditions, genetic testing strategies, and referral to clinical trials. Most respondents expressed interest in further education in these areas. A model for care is proposed as a first step in the education process.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.04.005},
	author = {Drack, Arlene V and Utz, Virginia Miraldi and Kai Wang and Alcorn, Deborah M and Brooks, Brian P and Costakos, Deborah M and Couser, Natario L and Heon, Elise and Levin, Alex V and Lloyd, I Christopher and Morse, Christie L and Schmitt, Melanie A and Whitman, Mary C and Traboulsi, Elias I}
}
@article {313161,
	title = {Seek and you shall remember: scene semantics interact with visual search to build better memories.},
	journal = {J Vis},
	volume = {14},
	number = {8},
	year = {2014},
	month = {2014},
	pages = {10},
	abstract = {Memorizing critical objects and their locations is an essential part of everyday life. In the present study, incidental encoding of objects in naturalistic scenes during search was compared to explicit memorization of those scenes. To investigate if prior knowledge of scene structure influences these two types of encoding differently, we used meaningless arrays of objects as well as objects in real-world, semantically meaningful images. Surprisingly, when participants were asked to recall scenes, their memory performance was markedly better for searched objects than for objects they had explicitly tried to memorize, even though participants in the search condition were not explicitly asked to memorize objects. This finding held true even when objects were observed for an equal amount of time in both conditions. Critically, the recall benefit for searched over memorized objects in scenes was eliminated when objects were presented on uniform, non-scene backgrounds rather than in a full scene context. Thus, scene semantics not only help us search for objects in naturalistic scenes, but appear to produce a representation that supports our memory for those objects beyond intentional memorization.},
	keywords = {Adult, Color Vision, Eye Movements, Female, Humans, Male, Memory, Long-Term, Mental Recall, Pattern Recognition, Visual, Semantics, Visual Acuity, Visual Perception},
	issn = {1534-7362},
	doi = {10.1167/14.8.10},
	author = {Draschkow, Dejan and Wolfe, Jeremy M and V{\~o}, Melissa L H}
}
@article {541256,
	title = {Preferential Budding of Vesicular Stomatitis Virus from the Basolateral Surface of Polarized Epithelial Cells Is Not Solely Directed by Matrix Protein or Glycoprotein.},
	journal = {J Virol},
	volume = {89},
	number = {22},
	year = {2015},
	month = {2015 Nov 15},
	pages = {11718-22},
	abstract = {Vesicular stomatitis virus has been shown to bud basolaterally, and the matrix protein, but not glycoprotein, was proposed to mediate this asymmetry. Using polarized T84 monolayers, we demonstrate that no single viral protein is sufficient for polarized budding. Particles are released from the apical and basolateral surfaces and are indistinguishable, indicating that there is no apical assembly defect. We propose that aspects of host cell polarity create a more efficient budding process at the basolateral surface.},
	issn = {1098-5514},
	doi = {10.1128/JVI.01658-15},
	author = {Drokhlyansky, Eugene and Soh, Timothy K and Cepko, Constance L}
}
@article {961681,
	title = {The brain parenchyma has a type I interferon response that can limit virus spread.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	number = {1},
	year = {2017},
	month = {2017 Jan 03},
	pages = {E95-E104},
	abstract = {The brain has a tightly regulated environment that protects neurons and limits inflammation, designated "immune privilege." However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate-putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1618157114},
	author = {Drokhlyansky, Eugene and G{\"o}z Ayt{\"u}rk, Didem and Soh, Timothy K and Chrenek, Ryan and O{\textquoteright}Loughlin, Elaine and Madore, Charlotte and Butovsky, Oleg and Cepko, Constance L}
}
@article {1364602,
	title = {Interview with Thaddeus P. Dryja, MD. Interviewed by George B. Bartley},
	journal = {Arch Ophthalmol},
	volume = {130},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {111-2},
	keywords = {Biomedical Research, Humans, Leadership, Ophthalmology, Physician Executives, United States},
	issn = {1538-3601},
	doi = {10.1001/archophthalmol.2011.382},
	author = {Dryja, Thaddeus P}
}
@article {836816,
	title = {The Clustered, Regularly Interspaced, Short Palindromic Repeats-associated Endonuclease 9 (CRISPR/Cas9)-created MDM2 T309G Mutation Enhances Vitreous-induced Expression of MDM2 and Proliferation and Survival of Cells.},
	journal = {J Biol Chem},
	volume = {291},
	number = {31},
	year = {2016},
	month = {2016 Jul 29},
	pages = {16339-47},
	abstract = {The G309 allele of SNPs in the mouse double minute (MDM2) promoter locus is associated with a higher risk of cancer and proliferative vitreoretinopathy (PVR), but whether SNP G309 contributes to the pathogenesis of PVR is to date unknown. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas) 9 from Streptococcus pyogenes (SpCas9) can be harnessed to manipulate a single or multiple nucleotides in mammalian cells. Here we delivered SpCas9 and guide RNAs using dual adeno-associated virus-derived vectors to target the MDM2 genomic locus together with a homologous repair template for creating the mutation of MDM2 T309G in human primary retinal pigment epithelial (hPRPE) cells whose genotype is MDM2 T309T. The next-generation sequencing results indicated that there was 42.51\% MDM2 G309 in the edited hPRPE cells using adeno-associated viral CRISPR/Cas9. Our data showed that vitreous induced an increase in MDM2 and subsequent attenuation of p53 expression in MDM2 T309G hPRPE cells. Furthermore, our experimental results demonstrated that MDM2 T309G in hPRPE cells enhanced vitreous-induced cell proliferation and survival, suggesting that this SNP contributes to the pathogenesis of PVR.},
	issn = {1083-351X},
	doi = {10.1074/jbc.M116.729467},
	author = {Duan, Yajian and Ma, Gaoen and Huang, Xionggao and D{\textquoteright}Amore, Patricia A and Zhang, Feng and Lei, Hetian}
}
@article {1402575,
	title = {Methicillin-resistant Staphylococcus aureus in acute otitis externa},
	journal = {World J Otorhinolaryngol Head Neck Surg},
	volume = {4},
	number = {4},
	year = {2018},
	month = {2018 Dec},
	pages = {246-252},
	abstract = {Objective: Otologic methicillin-resistant (MRSA) infection has historically been rare, but given the rise in community-acquired MRSA carriage and infection at other body sites, prevalence rates may be changing. The goal of this study was to determine the prevalence of MRSA in recent otologic cultures from patients with acute otitis externa (AOE). Study design: Retrospective review of an institutional microbiologic database. Methods: A retrospective analysis was performed on serial culture isolates taken from the ear at a quaternary care hospital from January 2014 to April 2016. The causative pathogen and antibiotic sensitivity was determined by culture isolation and end point mean inhibitory concentration (MIC) testing. Medical records were reviewed to document patient characteristics, chronicity of infection, symptomatology, and previous treatments. Results: Over the study period, 173 patients were diagnosed with AOE and underwent otologic cultures of the ear. Fifty-three (30.6\%) of cultures grew (SA). Of SA infections, 15 (28.3\%) were identified as MRSA. MRSA patients were typically older than patients with methicillin-sensitive SA (MSSA) (mean age 46.7\&nbsp;{\textpm}\&nbsp;17.9 29\&nbsp;{\textpm}\&nbsp;19.4, \&nbsp;=\&nbsp;0.003) and had more medical comorbidities (4 1.7, \&nbsp;=\&nbsp;0.001). Compared to patients with MSSA, patients with MRSA were significantly more likely to have had prior ototopical antibiotic exposure (37\% 73\%, \&nbsp;=\&nbsp;0.019). Conclusion: Contemporary ear culture isolates at quaternary care center show higher rates of MRSA compared to historical reports in the literature. Clinicians should consider ear cultures to identify MRSA AOE. Level of Evidence: IV.},
	issn = {2589-1081},
	doi = {10.1016/j.wjorl.2017.09.003},
	author = {Duarte, Maria J and Kozin, Elliott D and Bispo, Paulo J M and Mitchell, Andreas H and Gilmore, Michael S and Remenschneider, Aaron K}
}
@article {1538340,
	title = {Cortical plasticity in phantom limb pain: A fMRI study on the neural correlates of behavioral clinical manifestations},
	journal = {Psychiatry Res Neuroimaging},
	volume = {304},
	year = {2020},
	month = {2020 10 30},
	pages = {111151},
	abstract = {The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.},
	issn = {1872-7506},
	doi = {10.1016/j.pscychresns.2020.111151},
	author = {Duarte, D and Bauer, C C C and Pinto, C B and Saleh Velez, F G and Estudillo-Guerra, M A and Pacheco-Barrios, K and Gunduz, M E and Crandell, D and Merabet, L. and Fregni, F}
}
@article {416926,
	title = {Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity.},
	journal = {J Biol Chem},
	volume = {290},
	number = {17},
	year = {2015},
	month = {2015 Apr 24},
	pages = {11052-60},
	abstract = {By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca(2+)]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mm for ROS-GC1 and 39 mm for ROS-GC2. The effect required neither Ca(2+) nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca(2+)]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity.},
	issn = {1083-351X},
	doi = {10.1074/jbc.M115.650408},
	author = {Duda, Teresa and Wen, Xiao-Hong and Isayama, Tomoki and Sharma, Rameshwar K and Makino, Clint L}
}
@article {1474184,
	title = {GPR108 Is a Highly Conserved AAV Entry Factor},
	journal = {Mol Ther},
	volume = {28},
	number = {2},
	year = {2020},
	month = {2020 Feb 05},
	pages = {367-381},
	abstract = {Adeno-associated virus (AAV) is a highly promising gene transfer vector, yet major cellular requirements for AAV entry are poorly understood. Using a genome-wide CRISPR screen for entry of evolutionarily divergent serotype AAVrh32.33, we identified GPR108, a member of the G protein-coupled receptor superfamily, as an AAV entry factor. Of greater than 20 divergent AAVs across all AAV clades tested in human cell lines, only AAV5 transduction was unaffected in the GPR108 knockout (KO). GPR108 dependency was further shown in murine and primary cells in\&nbsp;vitro. These findings are further validated in\&nbsp;vivo, as the Gpr108 KO mouse demonstrates 10- to 100-fold reduced expression for AAV8 and rh32.33 but not AAV5. Mechanistically, both GPR108 N- and C-terminal domains are required for transduction, and on the capsid, a VP1 unique domain that is not conserved on AAV5 can be transferred to confer GPR108 independence onto AAV2 chimeras. In\&nbsp;vitro binding and fractionation studies indicate reduced nuclear import and cytosolic accumulation in the absence of GPR108. We thus have identified the second of two AAV entry factors that is conserved between mice and humans relevant both in\&nbsp;vitro and in\&nbsp;vivo, further providing a mechanistic understanding to the tropism of AAV gene therapy vectors.},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2019.11.005},
	author = {Dudek, Amanda M and Zabaleta, Nerea and Zinn, Eric and Pillay, Sirika and Zengel, James and Porter, Caryn and Franceschini, Jennifer Santos and Estelien, Reynette and Carette, Jan E and Zhou, Guo Ling and Vandenberghe, Luk H}
}
@article {1295860,
	title = {An Alternate Route for Adeno-associated Virus (AAV) Entry Independent of AAV Receptor},
	journal = {J Virol},
	volume = {92},
	number = {7},
	year = {2018},
	month = {2018 04 01},
	abstract = {Determinants and mechanisms of cell attachment and entry steer adeno-associated virus (AAV) in its utility as a gene therapy vector. Thus far, a systematic assessment of how diverse AAV serotypes engage their proteinaceous receptor AAVR (KIAA0319L) to establish transduction has been lacking, despite potential implications for cell and tissue tropism. Here, a large set of human and simian AAVs as well as -reconstructed ancestral AAV capsids were interrogated for AAVR usage. We identified a distinct AAV capsid lineage comprised of AAV4 and AAVrh32.33 that can bind and transduce cells in the absence of AAVR, independent of the multiplicity of infection. Virus overlay assays and rescue experiments in nonpermissive cells demonstrate that these AAVs are unable to bind to or use the AAVR protein for entry. Further evidence for a distinct entry pathway was observed , as AAVR knockout mice were equally as permissive to transduction by AAVrh32.33 as wild-type mice upon systemic injection. We interestingly observe that some AAV capsids undergo a low level of transduction in the absence of AAVR, both  and , suggesting that some capsids may have a multimodal entry pathway. In aggregate, our results demonstrate that AAVR usage is conserved among all primate AAVs except for those of the AAV4 lineage, and a non-AAVR pathway may be available to other serotypes. This work furthers our understanding of the entry of AAV, a vector system of broad utility in gene therapy. Adeno-associated virus (AAV) is a nonpathogenic virus that is used as a vehicle for gene delivery. Here, we have identified several situations in which transduction is retained in both cell lines and a mouse model in the absence of a previously defined entry receptor, AAVR. Defining the molecular determinants of the infectious pathway of this highly relevant viral vector system can help refine future applications and therapies with this vector.},
	keywords = {Animals, Capsid, Cell Line, Dependovirus, Genetic Vectors, Mice, Mice, Knockout, Receptors, Cell Surface, Transduction, Genetic, Virus Internalization},
	issn = {1098-5514},
	doi = {10.1128/JVI.02213-17},
	author = {Dudek, Amanda M and Pillay, Sirika and Puschnik, Andreas S and Nagamine, Claude M and Cheng, Fang and Qiu, Jianming and Carette, Jan E and Vandenberghe, Luk H}
}
@article {1417556,
	title = {Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways},
	journal = {Nat Commun},
	volume = {10},
	number = {1},
	year = {2019},
	month = {2019 01 14},
	pages = {299},
	abstract = {The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram.\&nbsp;In addition,\&nbsp;the original version of this Article also\&nbsp;contained errors\&nbsp;in the author affiliations which are detailed in the associated Publisher Correction.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-08078-w},
	author = {Duffy, David L and Zhu, Gu and Li, Xin and Sanna, Marianna and Iles, Mark M and Jacobs, Leonie C and Evans, David M and Yazar, Seyhan and Beesley, Jonathan and Law, Matthew H and Kraft, Peter and Visconti, Alessia and Taylor, John C and Liu, Fan and Wright, Margaret J and Henders, Anjali K and Bowdler, Lisa and Glass, Dan and Ikram, M Arfan and Uitterlinden, Andr{\'e} G and Madden, Pamela A and Heath, Andrew C and Nelson, Elliot C and Green, Adele C and Chanock, Stephen and Barrett, Jennifer H and Brown, Matthew A and Hayward, Nicholas K and Macgregor, Stuart and Sturm, Richard A and Hewitt, Alex W and Melanoma GWAS Consortium and Kayser, Manfred and Hunter, David J and Newton Bishop, Julia A and Spector, Timothy D and Montgomery, Grant W and Mackey, David A and Smith, George Davey and Nijsten, Tamar E and Bishop, D Timothy and Bataille, Veronique and Falchi, Mario and Han, Jiali and Martin, Nicholas G}
}
@article {913436,
	title = {Out of Sight: Culture-Negative Endocarditis and Endophthalmitis},
	journal = {Am J Med},
	volume = {130},
	number = {2},
	year = {2017},
	month = {2017 Feb},
	pages = {e51-e53},
	issn = {1555-7162},
	doi = {10.1016/j.amjmed.2016.08.029},
	author = {Dugdale, Caitlin and Brown, Sarah and Davila, Carine and Wolkow, Natalie and Fishbein, Gregory and Sun, Jennifer and Barkoudah, Ebrahim and Rawizza, Holly}
}
@article {560261,
	title = {Integrin-linked kinase regulates senescence in an Rb-dependent manner in cancer cell lines.},
	journal = {Cell Cycle},
	volume = {14},
	number = {18},
	year = {2015},
	month = {2015 Sep 17},
	pages = {2924-37},
	abstract = {Anti-integrin-linked kinase (ILK) therapies result in aberrant mitosis including altered mitotic spindle organization, centrosome declustering and mitotic arrest. In contrast to cells that expressed the retinoblastoma tumor suppressor protein Rb, we have shown that in retinoblastoma cell lines that do not express Rb, anti-ILK therapies induced aberrant mitosis that led to the accumulation of temporarily viable multinucleated cells. The present work was undertaken to: 1) determine the ultimate fate of cells that had survived anti-ILK therapies and 2) determine whether or not Rb expression altered the outcome of these cells. Our data indicate that ILK, a chemotherapy drug target is expressed in both well-differentiated, Rb-negative and relatively undifferentiated, Rb-positive retinoblastoma tissue. We show that small molecule targeting of ILK in Rb-positive and Rb-deficient cancer cells results in increased centrosomal declustering, aberrant mitotic spindle formation and multinucleation. However, anti-ILK therapies in vitro have different outcomes in retinoblastoma and glioblastoma cell lines that depend on Rb expression. TUNEL labeling and propidium iodide FACS analysis indicate that Rb-positive cells exposed to anti-ILK therapies are more susceptible to apoptosis and senescence than their Rb-deficient counterparts wherein aberrant mitosis induced by anti-ILK therapies exhibit mitotic arrest instead. These studies are the first to show a role for ILK in chemotherapy-induced senescence in Rb-positive cancer lines. Taken together these results indicate that the oncosuppressive outcomes for anti-ILK therapies in vitro, depend on the expression of the tumor suppressor Rb, a known G1 checkpoint and senescence regulator.},
	issn = {1551-4005},
	doi = {10.1080/15384101.2015.1064205},
	author = {Duminuco, Rose and Noble, Jake W and Goody, Joseph and Sharma, Manju and Ksander, Bruce R and Roskelley, Calvin D and Cox, Michael E and Mills, Julia}
}
@article {1323922,
	title = {Inherited Retinal Degenerations: Current Landscape and Knowledge Gaps},
	journal = {Transl Vis Sci Technol},
	volume = {7},
	number = {4},
	year = {2018},
	month = {2018 Jul},
	pages = {6},
	issn = {2164-2591},
	doi = {10.1167/tvst.7.4.6},
	author = {Duncan, Jacque L and Pierce, Eric A and Laster, Amy M and Daiger, Stephen P and Birch, David G and Ash, John D and Iannaccone, Alessandro and Flannery, John G and Sahel, Jos{\'e} A and Zack, Donald J and Zarbin, Marco A and and the Foundation Fighting Blindness Scientific Advisory Board}
}
@article {591236,
	title = {Quantitative Fundus Autofluorescence and Optical Coherence Tomography in ABCA4 Carriers.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {12},
	year = {2015},
	month = {2015 Nov 1},
	pages = {7274-85},
	abstract = {PURPOSE: To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus autofluorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort.

METHODS: Seventy-five individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9-82 years) were recruited as family members of affected patients from 46 unrelated families. For comparison, 57 affected family members with biallelic ABCA4 mutations (mean age, 23.4 years; range, 6-67 years) and two noncarrier siblings were also enrolled. Autofluorescence images (30{\textdegree}, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Horizontal SD-OCT scans through the fovea were obtained and the thicknesses of the outer retinal layers were measured.

RESULTS: In 60 of 65 carriers of ABCA4 mutations (age range, 9-60), qAF levels were within normal limits (95\% confidence level) observed for healthy noncarrier subjects, while qAF levels of affected family members were significantly increased. Perifoveal fleck-like abnormalities were observed in fundus AF images in four carriers, and corresponding changes were detected in the outer retinal layers in SD-OCT scans. Thicknesses of the outer retinal layers were within the normal range.

CONCLUSIONS: With few exceptions, individuals heterozygous for ABCA4 mutations and between the ages of 9 and 60 years do not present with elevated qAF. In a small number of carriers, perifoveal fleck-like changes were visible.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17371},
	author = {Duncker, Tobias and Stein, Gregory E and Lee, Winston and Tsang, Stephen H and Zernant, Jana and Bearelly, Srilaxmi and Hood, Donald C and Greenstein, Vivienne C and Delori, Fran{\c c}ois C and Allikmets, Rando and Sparrow, Janet R}
}
@article {439616,
	title = {Quantitative Fundus Autofluorescence and Optical Coherence Tomography in PRPH2/RDS- and ABCA4-Associated Disease Exhibiting Phenotypic Overlap.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {5},
	year = {2015},
	month = {2015 May 1},
	pages = {3159-70},
	abstract = {PURPOSE: To assess whether quantitative fundus autofluorescence (qAF), a measure of RPE lipofuscin, and spectral-domain optical coherence tomography (SD-OCT) can aid in the differentiation of patients with fundus features that could either be related to ABCA4 mutations or be part of the phenotypic spectrum of pattern dystrophies. METHODS: Autofluorescence images (30{\textdegree}, 488-nm excitation) from 39 patients (67 eyes) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference and were quantified as previously described. In addition, horizontal SD-OCT images through the fovea were obtained. Patients were screened for ABCA4 and PRPH2/RDS mutations. RESULTS: ABCA4 mutations were identified in 19 patients (mean age, 37 {\textpm} 12 years) and PRPH2/RDS mutations in 8 patients (mean age, 48 {\textpm} 13 years); no known ABCA4 or PRPH2/RDS mutations were found in 12 patients (mean age, 48 {\textpm} 9 years). Differentiation of the groups using phenotypic SD-OCT and AF features (e.g., peripapillary sparing, foveal sparing) was not reliable. However, patients with ABCA4 mutations could be discriminated reasonably well from other patients when qAF values were corrected for age and race. In general, ABCA4 patients had higher qAF values than PRPH2/RDS patients, while most patients without mutations in PRPH2/RDS or ABCA4 had qAF levels within the normal range. CONCLUSIONS: The high qAF levels of ABCA4-positive patients are a hallmark of ABCA4-related disease. The reason for high qAF among many PRPH2/RDS-positive patients is not known; higher RPE lipofuscin accumulation may be a primary or secondary effect of the PRPH2/RDS mutation.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-16343},
	author = {Duncker, Tobias and Tsang, Stephen H and Woods, Russell L and Lee, Winston and Zernant, Jana and Allikmets, Rando and Delori, Fran{\c c}ois C and Sparrow, Janet R}
}
@article {303866,
	title = {Quantitative Fundus Autofluorescence Distinguishes ABCA4-Associated and Non-ABCA4-Associated Bull{\textquoteright}s-Eye Maculopathy.},
	journal = {Ophthalmology},
	volume = {122},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {345-55},
	abstract = {PURPOSE: Quantitative fundus autofluorescence (qAF) and spectral-domain optical coherence tomography (SD OCT) were performed in patients with bull{\textquoteright}s-eye maculopathy (BEM) to identify phenotypic markers that can aid in the differentiation of ABCA4-associated and non-ABCA4-associated disease. DESIGN: Prospective cross-sectional study at an academic referral center. SUBJECTS: Thirty-seven BEM patients (age range, 8-60 years) were studied. All patients exhibited a localized macular lesion exhibiting a smooth contour and qualitatively normal-appearing surrounding retina without flecks. Control values consisted of previously published data from 277 healthy subjects (374 eyes; age range, 5-60 years) without a family history of retinal dystrophy. METHODS: Autofluorescence (AF) images (30{\textdegree}, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The grey levels (GLs) from 8 circularly arranged segments positioned at an eccentricity of approximately 7{\textdegree} to 9{\textdegree} in each image were calibrated to the reference (0 GL), magnification, and normative optical media density to yield qAF. In addition, horizontal SD OCT images through the fovea were obtained. All patients were screened for ABCA4 mutations using the ABCR600 microarray, next-generation sequencing, or both. MAIN OUTCOME MEASURES: Quantitative AF, correlations between AF and SD OCT, and genotyping for ABCA4 variants. RESULTS: ABCA4 mutations were identified in 22 patients, who tended to be younger (mean age, 21.9{\textpm}8.3 years) than patients without ABCA4 mutations (mean age, 42.1{\textpm}14.9 years). Whereas phenotypic differences were not obvious on the basis of qualitative fundus AF and SD OCT imaging, with qAF, the 2 groups of patients were clearly distinguishable. In the ABCA4-positive group, 37 of 41 eyes (19 of 22 patients) had qAF8 of more than the 95\% confidence interval for age. Conversely, in the ABCA4-negative group, 22 of 26 eyes (13 of 15 patients) had qAF8 within the normal range. CONCLUSIONS: The qAF method can differentiate between ABCA4-associated and non-ABCA4-associated BEM and may guide clinical diagnosis and genetic testing.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.08.017},
	author = {Duncker, Tobias and Tsang, Stephen H and Lee, Winston and Zernant, Jana and Allikmets, Rando and Delori, Fran{\c c}ois C and Sparrow, Janet R}
}
@article {1789211,
	title = {Eye Infections},
	journal = {N Engl J Med},
	volume = {389},
	number = {25},
	year = {2023},
	month = {2023 Dec 21},
	pages = {2363-2375},
	keywords = {Eye, Eye Infections, Eye Infections, Bacterial, Humans},
	issn = {1533-4406},
	doi = {10.1056/NEJMra2216081},
	author = {Durand, Marlene L and Barshak, Miriam B and Sobrin, Lucia}
}
@article {1619424,
	title = {Infectious Keratitis in 2021},
	journal = {JAMA},
	volume = {326},
	number = {13},
	year = {2021},
	month = {2021 Oct 05},
	pages = {1319-1320},
	keywords = {Acanthamoeba Keratitis, Contact Lenses, Eye Infections, Bacterial, Eye Infections, Fungal, Herpes Zoster Ophthalmicus, Humans, Keratitis, Keratitis, Herpetic, Risk Factors},
	issn = {1538-3598},
	doi = {10.1001/jama.2021.0424},
	author = {Durand, Marlene L and Barshak, Miriam Baron and Chodosh, James}
}
@article {1062821,
	title = {Bacterial and Fungal Endophthalmitis},
	journal = {Clin Microbiol Rev},
	volume = {30},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {597-613},
	abstract = {Endophthalmitis is a severe eye infection that may result in permanent loss of useful vision in the affected eye. Most cases are exogenous and occur as a complication of cataract surgery, an intravitreal injection, or penetrating ocular trauma. Endogenous endophthalmitis results from hematogenous seeding of the eye by bacteria or fungi, but bacteremia or fungemia may be transient and patients may present without symptoms of systemic infection. Nearly all endophthalmitis patients present with decreased vision, and some also have eye pain. Eye examination usually reveals a hypopyon and intraocular inflammation. Diagnosis is clinical, supported by cultures of the vitreous and/or aqueous or by blood cultures in some endogenous cases. Molecular diagnostic techniques have been used in research laboratories for pathogen identification in endophthalmitis and offer the possibility of rapid diagnosis, including in culture-negative cases. Intravitreal injection of antibiotics is the most important component of treatment; some cases also benefit from surgical debridement of the vitreous by a vitrectomy. The visual outcome depends partly on the pathogen: coagulase-negative staphylococcal endophthalmitis has a better prognosis than does streptococcal endophthalmitis, for example. Endophthalmitis is a medical emergency, and prompt diagnosis and treatment are essential for saving vision.},
	issn = {1098-6618},
	doi = {10.1128/CMR.00113-16},
	author = {Durand, Marlene L}
}
@article {1233401,
	title = {Authors reply to Letter to the Editor- In response to: Comment on Durrani et al."s "Adalimumab for Ocular Inflammation"},
	journal = {Ocul Immunol Inflamm},
	year = {2017},
	month = {2017 Oct 18},
	pages = {1},
	issn = {1744-5078},
	doi = {10.1080/09273948.2017.1379545},
	author = {Durrani, Khayyam and Kempen, John H and Foster, C Stephen and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Research Group}
}
@article {1364603,
	title = {Fundus autofluorescence imaging in posterior uveitis},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {228-35},
	abstract = {Although the phenomenon of fundus autofluorescence has been known for decades, it has only recently been recognized as a measure of retinal pigment epithelial function and health. Characteristic fundus autofluorescence patterns have been described in eyes affected by inflammation of the posterior segment, and these patterns have provided insights into the pathogenesis of posterior uveitis entities. In addition, preliminary data indicate that fundus autofluorescence characteristics may serve as markers of disease activity, allow prediction of visual prognosis, and may help determine the adequacy of therapy. We provide an overview of the current state of fundus autofluorescence imaging technology and review our current knowledge of fundus autoflourescence findings and their clinical use in the posterior uveitis entities.},
	keywords = {Fundus Oculi, Humans, Lipofuscin, Optical Imaging, Prognosis, Retinal Pigment Epithelium, Uveitis, Posterior},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.711414},
	author = {Durrani, Khayyam and Foster, C Stephen}
}
@article {680406,
	title = {Adalimumab for Ocular Inflammation.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Mar 22},
	pages = {1-8},
	abstract = {PURPOSE: To evaluate adalimumab as an immunomodulatory treatment for non-infectious ocular inflammatory diseases. METHODS: Characteristics of patients treated with adalimumab were abstracted in a standardized chart review. Main outcomes measured were control of inflammation, corticosteroid-sparing effect, and visual acuity. RESULTS: In total, 32 patients with ocular inflammation were treated with adalimumab. The most common ophthalmic diagnoses were anterior uveitis, occurring in 15 patients (47\%), and scleritis, occurring in 9 patients (28\%). At 6 months of therapy, among 15 eyes with active inflammation, 7 (47\%) became completely inactive, and oral prednisone was reduced to <=10 mg/day in 2 of 4 patients (50\%). On average, visual acuity decreased by 0.13 lines during the first 6 months of treatment. Adalimumab was discontinued because of lack of effectiveness in four patients within 6 months. CONCLUSIONS: Adalimumab was moderately effective in controlling inflammation in a group of highly pre-treated cases of ocular inflammatory disease.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2015.1134581},
	author = {Durrani, Khayyam and Kempen, John H and Ying, Gui-Shuang and Kacmaz, R Oktay and Artornsombudh, Pichaporn and Rosenbaum, James T and Suhler, Eric B and Thorne, Jennifer E and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Foster, C Stephen and Foster, C Stephen}
}
@article {1532325,
	title = {An update on autoimmune retinopathy},
	journal = {Indian J Ophthalmol},
	volume = {68},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {1829-1837},
	abstract = {Autoimmune retinopathy (AIR) refers to a group of rare autoimmune retinal degenerative diseases presumably caused by cross-reactivity of serum autoantibodies against retinal antigens. The pathogenesis of AIR remains largely presumptive and there are a significant number of antiretinal antibodies that have been detected in association with AIR. The diagnosis of AIR is largely based on the demonstration of antiretinal antibodies in the serum along with suggestive clinical features and ancillary investigations. A high index of suspicion along with early diagnosis and treatment may play a critical role to lower the risk of irreversible immunological damage to the retinal cells in these patients. A multi-disciplinary approach for complete management and evaluation is helpful in such conditions. Various therapeutic options have been described for the treatment of AIR, though there is no consensus on standard treatment protocol.},
	issn = {1998-3689},
	doi = {10.4103/ijo.IJO_786_20},
	author = {Dutta Majumder, Parthopratim and Marchese, Alessandro and Pichi, Francesco and Garg, Itika and Agarwal, Aniruddha}
}
@article {1511500,
	title = {Characterizing the Impact of Fear of Falling on Activity and Falls in Older Adults with Glaucoma},
	journal = {J Am Geriatr Soc},
	volume = {68},
	number = {8},
	year = {2020},
	month = {2020 Aug},
	pages = {1847-1851},
	abstract = {OBJECTIVE: Fear of falling (FoF) may alter mobility in older adults, especially among those with visual impairment. Using a longitudinal prospective cohort of older glaucoma patients, we investigated whether and how FoF is associated with future falls and physical activity. DESIGN: Prospective observational cohort study. SETTING: Hospital-based single-center recruitment. PARTICIPANTS: Individuals with glaucoma or suspected glaucoma. MEASUREMENTS: FoF was measured annually over a 3-year period using the University of Illinois at Chicago FoF Questionnaire, with lower Rasch-analyzed FoF scores (in logit units) indicating less fear. Participants recorded falls prospectively over the 3-year period using monthly mail-in calendars. Daily steps were collected annually over 7 days using an accelerometer. Visual field (VF) sensitivity was derived by combining sensitivities from monocular VF results. Participants completed questionnaires to determine other demographic/health characteristics. Multivariate random effects models evaluated within-participant changes in fall rates and physical activity across study years. RESULTS: At lower FoF levels (FoF<=0), each one-unit worsening in FoF score across study years was associated with 2.73 times higher odds of reporting at least one fall in the next year (95\% confidence interval [CI] = 1.55-4.81) but was not associated with average daily steps (P = .44). Similar results were seen when fall rates were normalized by number of steps taken (P = .97). At higher FoF levels (FoF \&gt; 0), inter-year changes in FoF scores were not significantly associated with reporting a fall in the following year (P = .78) but were associated with 407 fewer average daily steps per one-unit change in FoF (95\% CI = -743 to -71). CONCLUSION: FoF is an important psychological factor associated with mobility in glaucoma patients, although specific aspects of mobility (fall rates vs activity levels) affected vary by the degree of FoF. Our findings suggest that customizing behavioral interventions for older adults based on their levels of FoF may be an important strategy for fall prevention and activity promotion. J Am Geriatr Soc 68:1847-1851, 2020.},
	issn = {1532-5415},
	doi = {10.1111/jgs.16516},
	author = {E, Jian-Yu and Mihailovic, Aleksandra and Kuo, Pei-Lun and West, Sheila K and Friedman, David S and Gitlin, Laura N and Li, Tianjing and Schrack, Jennifer A and Ramulu, Pradeep Y}
}
@article {1573118,
	title = {Characterizing Longitudinal Changes in Physical Activity and Fear of Falling after Falls in Glaucoma},
	journal = {J Am Geriatr Soc},
	volume = {69},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {1249-1256},
	abstract = {BACKGROUND: Older adults with visual impairments experience a higher risk of falling, and are more vulnerable to adverse health consequences associated with falls than those with normal vision. This study characterizes longitudinal changes in objectively measured physical activity and fear of falling (FoF) occurring after various types of falls in visually impaired older adults. DESIGN: Prospective cohort study. SETTING: Hospital-based enrollment. PARTICIPANTS: People with glaucoma or suspected glaucoma. MEASUREMENTS: Falls were defined as unintentionally coming to rest on the ground or a lower level, and injurious falls were determined though follow-up calls. Study participants were categorized into three groups-fallers with injurious consequences, fallers without injurious consequences, and non-fallers based on fall status in the first year. Physical activity was assessed by waist-bound accelerometer. FoF was evaluated by questionnaire, with Rasch modeling generating FoF scores where higher scores reflected worse FoF. The 3-year longitudinal changes of physical activity and FoF were modeled using mixed-effects models. RESULTS: In linear models fully adjusted for visual field damage and other covariates, physical activity among injurious fallers showed greater annual (per year) declines in daily steps (-425 steps/d, 95\% confidence interval (CI) = -793, -57), daily active minutes (-13 min/d, 95\% CI = -21, -6), and daily moderate and vigorous physical activity (MVPA) minutes (-3 MVPA minutes/d, 95\% CI = -5, 0) over the 3-year period as compared to non-fallers; however, physical activity did not significantly decline among non-injurious fallers. No longitudinal increases in FoF scores were observed in injurious or non-injurious fallers when compared to non-fallers. CONCLUSION: Among visually impaired older adults, injurious falls identified prospectively over 12 months contributed to a significant decline in physical activity over a 3-year period, while minimal changes were observed in FoF.},
	issn = {1532-5415},
	doi = {10.1111/jgs.17014},
	author = {E, Jian-Yu and Mihailovic, Aleksandra and Schrack, Jennifer A and Li, Tianjing and Friedman, David S and West, Sheila K and Gitlin, Laura N and Ramulu, Pradeep Y}
}
@article {1593853,
	title = {Importance and severity dependence of physical activity by GPS-tracked location in glaucoma patients: GPS-tracked physical activity in glaucoma},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 May 13},
	abstract = {PURPOSE: To quantify the association of visual field (VF) damage on physical activity away-from-home, per away-from-home excursion, and at home. DESIGN: Prospective cohort study. METHODS: Among 229 participants with glaucoma or suspected glaucoma, severity of VF damage was defined as average sensitivity within the integrated VF (IVF). Participants wore accelerometers and GPS trackers for seven days to measure physical activity and characterize activity location. Multivariable negative binomial regressions were used to test whether away-from-home activity per day, physical activity per away-from-home excursion, and at home activity per day varied by severity of VF damage. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with a lower amount of away-from-home activities per day [18\% less Moderate \&amp; Vigorous Physical Activity (MVPA) minutes/day, 95\% CI, 0.69 to 0.97], and physical activities per away-from-home excursion (20\% less MVPA minutes/excursion, 95\% CI, 0.65, 0.98). Similar findings were noted for other away-from-home activity measures (including active minutes/steps per day, or active minutes/steps per excursion). However, worse IVF sensitivity was not associated with measures of at home activities (MVPA minutes/day, active minutes/day, and steps/day), time spent at or away from home, or excursions/week (p\&gt;0.1 for all). CONCLUSIONS: Restriction of physical activity in more severe glaucoma patients results mostly from activity restriction outside home environment. These findings highlight the importance of maintaining a safe home environment (where activity is less restricted) and increasing confidence to perform activity, particular high intensity activity, when leaving the home amongst patients with glaucoma.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.04.032},
	author = {E, Jian-Yu and Mihailovic, Aleksandra and Garzon, Catalina and Schrack, Jennifer A and Li, Tianjing and West, Sheila K and Friedman, David S and Gitlin, Laura N and Ramulu, Pradeep Y}
}
@article {1603843,
	title = {Association Between Visual Field Damage and Gait Dysfunction in Patients With Glaucoma},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {10},
	year = {2021},
	month = {2021 Oct 01},
	pages = {1053-1060},
	abstract = {Importance: Gait dysfunction is common in older people with visual impairment and is a major cause of falls. Objective: To compare 3-year longitudinal changes in gait measures across the spectrum of baseline visual field (VF) damage in glaucoma. Design, Setting, and Participants: A post hoc analysis was designed on September 1, 2018, following a prospective cohort study, which enrolled older adults with glaucoma or suspected glaucoma from September 2013 to March 2015 and followed up for up to 3 years. Baseline VF damage was defined by integrated VF (IVF) sensitivity and categorized as normal/mild (IVF \&gt;28 dB), moderate (IVF, 23-28 dB), and severe (IVF, \&lt;23 dB). Each participant walked on an electronic walkway back and forth twice at normal pace each study year. Linear mixed-effects models evaluated longitudinal change in gait outcomes (1) stratified within each VF severity category and (2) across the range of IVF sensitivity. Analysis took place from October 2019 to October 2020. Main Outcomes and Measures: Three-year changes in 7 gait assessments under usual-pace walking, including base support and its coefficient of variation, stride length and its coefficient of variation, stride velocity and its coefficient of variation, and cadence. Results: Of 241 participants, the mean (SD) age was 70.8 (7.7) years, 116 (48.2\%) were women, and 70 (29.0\%) were African American. When comparing longitudinal gait changes over 3 years across the spectrum of IVF sensitivity, each 5-unit (dB) decrement was associated with more rapid declines in stride velocity (-0.05 z score unit/y; 95\% CI, -0.09 to -0.01; P = .01) and cadence (-0.07 z score unit/y; 95\% CI, -0.10 to -0.03; P \&lt; .001). When evaluating gait changes within each glaucoma severity group, shorter stride length was associated with persons with normal/mild (-0.06 z score unit/y; 95\% CI, -0.10 to -0.03; P = .001), moderate (-0.08 z score unit/y; 95\% CI, -0.12 to -0.04; P \&lt; .001), and severe VF damage (-0.16 z score unit/y; 95\% CI, -0.24 to -0.07; P \&lt; .001), while stride velocity (-0.18 z score unit; 95\% CI, -0.28 to -0.07; P = .002) and slower cadence (-0.15 z score unit; 95\% CI, -0.25 to -0.04; P = .006) were associated with those with severe VF damage. Conclusions and Relevance: At worse levels of baseline VF damage, patients with glaucoma in this study demonstrated an exacerbated decline in walking speeds (ie, stride velocity and cadence), indicating that mobility speeds decrease faster over time in older adults with glaucoma.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.2617},
	author = {E, Jian-Yu and Mihailovic, Aleksandra and Garzon, Catalina and Schrack, Jennifer A and Li, Tianjing and West, Sheila K and Gitlin, Laura N and Friedman, David S and Ramulu, Pradeep Y}
}
@article {1619428,
	title = {Longitudinal changes in daily patterns of objectively measured physical activity after falls in older adults with varying degrees of glaucoma},
	journal = {EClinicalMedicine},
	volume = {40},
	year = {2021},
	month = {2021 Oct},
	pages = {101097},
	abstract = {Background: Visually impaired older adults have a greater risk of falling, making them particularly susceptible to fall-related health consequences and restricted physical activity. Unclear however, is the relationship between having falls and longitudinal changes in daily patterns of objectively measured physical activity in older adults with visual impairments. Methods: We created a three-year prospective cohort study (Falls in Glaucoma Study) of older adults with primary or suspected glaucoma at the Johns Hopkins Wilmer Eye Institute from 2013 to 2015. Cumulative incidence of falls was determined through self-reported fall calendars over 12 months. Participants were then classified into one of three groups: multiple fallers (>=2 falls), single fallers (1 fall), and non-fallers (0). Daily physical activity was measured over 1 week using a waist-bound accelerometer during baseline and three-year follow-ups. Activity fragmentation was defined as the reciprocal of the mean activity bout length, with higher fragmentation reflecting shorter, more fractured bouts of continuous activity. Multivariate linear mixed-effects models were used to assess three-year longitudinal changes in: 1) activity fragmentation, and 2) accumulation of activity across six three-hour intervals from 5 AM to 11 PM. Findings: In adjusted models accounting for visual field damage and other factors, multiple fallers demonstrated greater annual declines (per year) in daily active bouts (-1.79 bouts/day, 95\% confidence interval [CI]: -3.35, -0.22), daily active minutes (-17.15\&nbsp;min/day, 95\% CI: -26.35, -7.94), and increased fragmentation (1\%, 95\% CI: 0, 2\%) over the three-year follow-up period as compared to non-fallers; no such changes were seen when comparing single fallers and non-fallers. In time-of-day analyses, multiple fallers experienced greater annual declines in average hourly steps over all periods of the day, though the rate of decline was only significant between 5 PM and 8 PM (-27.07 steps/hour, 95\% CI: -51.15, -2.99) compared to non-fallers. Interpretation: In an older population with visual impairment, multiple falls over 12 months were associated with more transient and fragmented activity over a subsequent three-year period, and activity declines during evening hours, compared to non-fallers. These findings suggest that multiple fallers with visual impairment may be at high risk for a decline in physical capacity and endurance, warranting clinical interventions. Funding: The research was supported in part by National Institutes of Health Grant EY022976.},
	issn = {2589-5370},
	doi = {10.1016/j.eclinm.2021.101097},
	author = {E, Jian-Yu and Mihailovic, Aleksandra and Schrack, Jennifer A and Garzon, Catalina and Li, Tianjing and Friedman, David S and West, Sheila K and Gitlin, Laura N and Ramulu, Pradeep Y}
}
@article {1367189,
	title = {Bitemporal hemianopia; its unique binocular complexities and a novel remedy},
	journal = {Ophthalmic Physiol Opt},
	volume = {34},
	number = {2},
	year = {2014},
	pages = {233-42},
	author = {Peli E and Satgunam P}
}
@article {1573108,
	title = {Patterns of Daily Physical Activity across the Spectrum of Visual Field Damage in Glaucoma Patients},
	journal = {Ophthalmology},
	volume = {128},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {70-77},
	abstract = {PURPOSE: To define and quantify patterns of objectively measured daily physical activity by level of visual field (VF) damage in glaucoma patients including: (1) activity fragmentation, a metric of health and physiologic decline, and (2) diurnal patterns of activity, a measure of rest and activity rhythms. DESIGN: Prospective cohort study. PARTICIPANTS: Older adults diagnosed with glaucoma or suspected glaucoma. METHODS: Degree of VF damage was defined by the average VF sensitivity within the integrated VF (IVF). Each participant wore a hip accelerometer for 1 week to measure daily minute-by-minute activity for 7 consecutive days. Activity fragmentation was calculated as the reciprocal of the average activity bout duration in minutes, with higher fragmentation indicating more transient, rather than sustained, activity. Multivariate linear regression was used to test for cross-sectional associations between VF damage and activity fragmentation. Multivariate linear mixed-effects models were used to assess the associations between VF damage and accumulation of activity across 6 3-hour intervals from 5 am to 11 pm. MAIN OUTCOME MEASURES: Activity fragmentation and amount of activity (steps) over the course of the day. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with 16.3 fewer active minutes/day (P \&lt; 0.05) and 2\% higher activity fragmentation (P \&lt; 0.05), but not with the number of active bouts per day (P\&nbsp;= 0.30). In time-of-day analyses, lower IVF sensitivity was associated with fewer steps over the 11 am to 2 pm, 2 pm to 5 pm, and 5 pm to 8 pm periods (106.6, 93.1, and 89.2 fewer steps, respectively; P \&lt; 0.05 for all), but not over other periods. The activity midpoint (the time at which half of the daily activity is completed) did not vary across level of VF damage. CONCLUSIONS: At worse levels of VF damage, glaucoma patients demonstrate shorter, more fragmented bouts of physical activity throughout the day and lower activity levels during typical waking hours, reflecting low physiologic functioning. Further work is needed to establish the temporality of this association and whether glaucoma patients with such activity patterns are at a greater risk of adverse health outcomes associated with activity fragmentation.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.06.053},
	author = {E, Jian-Yu and Schrack, Jennifer A and Mihailovic, Aleksandra and Wanigatunga, Amal A and West, Sheila K and Friedman, David S and Gitlin, Laura N and Li, Tianjing and Ramulu, Pradeep Y}
}
@article {836821,
	title = {A Novel NOD2-associated Mutation and Variant Blau Syndrome: Phenotype and Molecular Analysis.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Jul 15},
	pages = {1-8},
	abstract = {PURPOSE: To describe the clinical and molecular implications of a novel mutation in the NOD2/CARD15 gene on a family and its seven affected members. METHODS: We reviewed the clinical presentations of family members who came to our center for refractory uveitis. Genetic testing and molecular testing was performed. RESULTS: All affected members had adult onset recurrent non-granulomatous panuveitis. The inheritance pattern suggested an autosomal dominant disease and genetic analysis identified a novel mutation in the NOD2 gene that converted amino acid 600 from glutamate to alanine (E600A). Transfection of the E600A NOD2 into human embryonic kidney-293 (HEK293) cells revealed constitutive activation and a reduced ability to respond to the NOD2 ligand, muramyl dipeptide (MDP) as compared with wild-type NOD2. CONCLUSIONS: The E600A mutation in the NOD2 gene may confer a higher penetrance of uveitis but a later onset of milder forms of non-ocular involvement.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2016.1185529},
	author = {Ebrahimiadib, Nazanin and Abusamra, Khawla and Domina, Aaron M and Stiles, Ethan R and Ewer, Roger and Bocian, Charlie P and Foster, C Stephen}
}
@article {1333849,
	title = {Atypical Perinuclear Anti-Neutrophil Cytoplasmic Antibodies in Ocular Inflammatory Diseases},
	journal = {Ocul Immunol Inflamm},
	year = {2018},
	month = {2018 Sep 19},
	pages = {1-5},
	abstract = {PURPOSE: To characterize the clinical features of patients with ocular inflammatory diseases (OID) who tested positive for atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). METHODS: Retrospective case series of patients with OID seen at the Massachusetts Eye Research and Surgery Institute (MERSI) from April 2014 to April 2016. RESULTS: 813 patients were tested for ANCA with 34 patients (4\%) being positive for atypical P-ANCA. Among those with positive atypical P-ANCA, the most frequent diagnoses were anterior uveitis in 62\% (n\&nbsp;=\&nbsp;21) followed by scleritis in 20\% (n\&nbsp;=\&nbsp;7). Only one patient had an episode of recurrent disease flare-up. All but one patient, who had concomitant C-ANCA seropositivity and granulomatosis with polyangiitis, had a favorable disease course with controlled inflammation using topical and/or systemic immunomodulatory therapy. CONCLUSION: In contrast to typical C-ANCA and P-ANCA, atypical P-ANCA seropositivity was not associated with severe vasculitis or poor prognosis in patients with the OID.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2018.1502787},
	author = {Ebrahimiadib, Nazanin and Ma, Lina and Modjtahedi, Bobeck S and Davoudi, Samaneh and Rahmani, Safa and Syeda, Sarah and Stephenson, Andrew and Foster, Charles Stephen}
}
@article {1603853,
	title = {COVID-19 and Immunosuppressive Therapy in Ocular Inflammatory Disease, a Telemedicine Survey},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Jul 30},
	pages = {1-7},
	abstract = {Purpose: Determine the risk of immunomodulatory therapy (IMT) for COVID-19 infection morbidity.Method: A telemedicine survey on patients of a referral uveitis clinic was performed. Signs of infection, habits, and hospitalizations during the 7\&nbsp;months of the COVID-19 pandemic prior to the study date were recorded. Suggestive findings in chest CT scan and/or positive RT-PCR were considered as confirmed COVID-19 infection while those with only suggestive symptoms were considered as suspected cases. Risk factors including sanitary measures and IMT were compared between patients with confirmed cases and patients without infection.Result: 694 patients were included. Eight patients were identified as confirmed cases and 22 patients as suspected cases of COVID-19 infection. Close contact with infected persons was the only significant risk factor for contracting COVID-19.Conclusion: Using IMT did not affect hospitalization and/or ICU admission and can thus be continued during the pandemic, provided that instructions for preventive measures are followed.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2021.1949477},
	author = {Ebrahimiadib, Nazanin and Fadakar, Kaveh and Riazi-Esfahani, Hamid and Zarei, Mohammad and Maleki, Arash and Bojabadi, Leila and Ahmadi, Amin and Look-Why, Sydney and Foster, Charles Stephen}
}
@article {1573107,
	title = {Vascular abnormalities in uveitis},
	journal = {Surv Ophthalmol},
	volume = {66},
	number = {4},
	year = {2021},
	month = {2021 Jul-Aug},
	pages = {653-667},
	abstract = {Inflammation can involve several ocular structures, including the sclera, retina, and uvea, and cause vascular changes in these tissues. Although retinal vasculitis is the most common finding associated with uveitis involving the posterior segment, other vascular abnormalities may be seen in the retina. These include capillary nonperfusion and ischemia, vascular occlusions, preretinal neovascularization, microaneurysms and macroaneurysms, and telangiectasia. Moreover, vasoproliferative tumors and subsequent coat-like response can develop secondary to uveitis. Fluorescein angiography is ideal for the investigation of retinal vascular leakage and neovascularization, while optical coherence tomography angiography can provide depth resolved images from the superficial and deep capillary plexus and can demonstrate vascular remodeling. Choroidal vascular abnormalities primarily develop in the choriocapillaris or in the choroidal stroma and can appear as flow void in optical coherence tomography angiography and filling defect and vascular leakage in indocyanine green angiography. Extensive choriocapillaris nonperfusion in the presence of choroidal inflammation can increase the risk of choroidal neovascular membrane development. Iris vascular changes may manifest as dilation of vessels in stroma due to inflammation or rubeosis that is usually from ischemia in retinal periphery secondary to chronic inflammation. More severe forms of scleral inflammation, such as necrotizing scleritis, are associated with vascular occlusion in the deep episcleral plexus, which can lead to necrosis of sclera layer and uveal exposure.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2020.12.006},
	author = {Ebrahimiadib, Nazanin and Maleki, Arash and Fadakar, Kaveh and Manhapra, Ambika and Ghassemi, Fariba and Foster, C Stephen}
}
@article {1295861,
	title = {Atopy in Patients With Ocular Cicatricial Pemphigoid},
	journal = {Cornea},
	volume = {37},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {436-441},
	abstract = {PURPOSE: To evaluate the presence of atopy in patients with ocular cicatricial pemphigoid (OCP).

METHOD: Patient encounters between August 2005 and November 2016 at the Massachusetts Eye Research and Surgery Institute (MERSI) were searched to identify those with biopsy-proven OCP who had concurrent evidence of atopy.

RESULTS: There were 230 patients with biopsy-proven OCP. Thirty-three of them were found to have clinical symptoms of atopy (asthma, hay fever, and eczema) and of these, 23 had evidence of atopy in their conjunctival biopsy specimens. All patients were administered immunomodulatory therapy for treatment of their OCP with 20 patients requiring additional antiallergy treatment to control residual atopic ocular symptoms. Among patients who used antiallergy medications, 80\% showed improvement in residual symptoms. Rituximab and/or intravenous immunoglobulin is a preferred OCP medication for patients with OCP with some evidence of atopy.

CONCLUSIONS: Clinicians should consider the coexistence of atopy in patients with OCP, especially in those with persistent symptoms after initiation of immunomodulatory therapy.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001477},
	author = {Ebrahimiadib, Nazanin and Hernandez, Mikhail and Modjtahedi, Bobeck S and Roohipoor, C Ramak and Foster, C Stephen}
}
@article {931046,
	title = {Treatment of Serpiginous Choroiditis with Chlorambucil: A Report of 17 Patients.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Oct 18},
	pages = {1-11},
	abstract = {PURPOSE: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis. METHODS: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3.0-4.5 {\texttimes} 10(9) cells/L. The goal of therapy was to maintain this value for at least 6-9 months. Adverse effects, recurrence, rate of new choroidal neovascularization (CNVM), and visual acuity before and after treatment were recorded. RESULTS: The mean age of the 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil was 46 years, and six patients (35\%) were male. The mean duration of treatment for chlorambucil was 8.4 months. None of them developed cancer or persistent side-effects, with a mean follow-up of 53 months. Of the patients, 12 (71\%) achieved an average of 45 (5-120) months drug-free remission in their last follow-up. Visual acuity of 33 treated eyes remained within two lines of Snellen acuity in 27 eyes (82\%), improved in one eye (3\%), and deteriorated in five eyes (15\%). Leukopenia was the most common side-effect, which was reversible in all cases. CONCLUSIONS: Chlorambucil in a relatively short duration of time, with an escalating dose guided by weekly WBC was well tolerated, as well as effective in preventing recurrence and maintaining vision in patients with serpiginous choroiditis.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2016.1214737},
	author = {Ebrahimiadib, Nazanin and Modjtahedi, Bobeck S and Davoudi, Samaneh and Foster, C Stephen}
}
@article {753681,
	title = {Successful Treatment Strategies in Granulomatosis With Polyangiitis-Associated Peripheral Ulcerative Keratitis.},
	journal = {Cornea},
	volume = {35},
	number = {11},
	year = {2016},
	month = {2016 Nov},
	pages = {1459-1465},
	abstract = {PURPOSE: Management of granulomatosis with polyangiitis (GPA)-associated peripheral ulcerative keratitis (PUK) is challenging and lacks definite guidelines. We aimed to summarize our treatment and outcome experience with patients with GPA-PUK. METHODS: The Massachusetts Eye Research and Surgery Institution patient database was searched from 2005 to 2015 to identify patients with diagnosis of PUK who suffered from GPA. Individual patient histories were examined, and treatment strategies and outcomes were summarized. RESULTS: There were 16 patients who started treatment with a mean duration follow-up of 64 months (range: 12-110 mo). Rituximab and cyclophosphamide, either alone or in combination with other agents, were the most successful agents in controlling inflammation. Rituximab was administered in 11 patients with remission being achieved in all. Cyclophosphamide successfully controlled inflammation in 50\% (5/10). Two of the patients (2/5, 40\%) who had achieved initial control on cyclophosphamide had flares of their PUK. Two of 11 (18\%) patients on rituximab had flares of scleritis and orbital inflammation but not PUK. Two patients, one in each treatment group, stopped treatment after achieving remission after 6 months of therapy but suffered disease recurrence within 2 months of treatment cessation. CONCLUSIONS: Rituximab achieved a high rate of disease control in PUK patients with GPA and is the preferred agent in halting disease progression.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000919},
	author = {Ebrahimiadib, Nazanin and Modjtahedi, Bobeck S and Roohipoor, Ramak and Anesi, Stephen D and Foster, C Stephen}
}
@article {742246,
	title = {Internet-based versus Conventional Referral System for Retinopathy of Prematurity Screening in Iran.},
	journal = {Ophthalmic Epidemiol},
	volume = {23},
	number = {5},
	year = {2016},
	month = {2016 Oct},
	pages = {292-7},
	abstract = {PURPOSE: To compare the efficacy of an internet-based versus traditional referral system for retinopathy of prematurity (ROP) screening in Iran. METHODS: Two referral screening systems were compared in this prospective observational study. Group A (internet-based) comprised premature babies who were registered into an online system for screening. Their appointments were scheduled automatically based on standardized criteria. Group B (conventional) comprised premature babies whose referrals were based on oral or written recommendations. Babies were referred based on standard criteria (gestational age, GA, \&lt;37 weeks or birth weight \&lt; 3000 g). RESULTS: A total of 2115 neonates were screened between October 2011 and October 2012. From these 1896 met the inclusion criteria (group A n = 856, group B n = 1040). Time of first examination for neonates with GA<=27 weeks was 30.07{\textpm} 2.72 weeks postmenstrual age in group A and 38.52{\textpm} 7.03 weeks in group B (p = 0.049), and for neonates with GA\&gt;27 weeks was 4.86 {\textpm}1.77 and 8.16 {\textpm}4.93 weeks after birth in groups A and B, respectively (p \&lt; 0.001). All registered babies in group A attended their first screening exam. One case (0.1\%) of advanced ROP developed in group A (in a patient with poor follow-up compliance), whereas advanced stages of ROP were seen in 26 cases (2.5\%) in group B (p \&lt; 0.001). CONCLUSION: An internet-based registration system for ROP screening resulted in fewer cases of delayed first examination and resulted in fewer babies with advanced ROP.},
	issn = {1744-5086},
	doi = {10.3109/09286586.2015.1136653},
	author = {Ebrahimiadib, Nazanin and Roohipour, Ramak and Karkhaneh, Reza and Farahani, Afsar and Riazi Esfahani, Mohammad and Khodabande, Alireza and Zarei, Mohammad and Taheri, Arash and Imani Fouladi, Marjan and Yaseri, Mehdi and Modjtahedi, Bobeck S}
}
@article {1351158,
	title = {Cataract development in Norwegian patients with congenital aniridia},
	journal = {Acta Ophthalmol},
	volume = {92},
	number = {2},
	year = {2014},
	month = {2014 Mar},
	pages = {e165-7},
	keywords = {Adolescent, Adult, Aniridia, Cataract, Cataract Extraction, Child, Child, Preschool, Humans, Middle Aged, Norway, Phenotype, Time Factors, Young Adult},
	issn = {1755-3768},
	doi = {10.1111/aos.12225},
	author = {Ed{\'e}n, Ulla and Lagali, Neil and Dellby, Anette and Utheim, Tor P and Riise, Ruth and Chen, Xiangjun and Fagerholm, Per}
}
@article {1559556,
	title = {Acadesine suppresses TNF-α induced complement component 3 (C3), in retinal pigment epithelial (RPE) cells},
	journal = {PLoS One},
	volume = {15},
	number = {12},
	year = {2020},
	month = {2020},
	pages = {e0244307},
	abstract = {RATIONALE: Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness in the developed world. Aging, inflammation and complement dysregulation affecting the retinal pigment epithelium (RPE), are considered significant contributors in its pathogenesis and several evidences have linked tumor necrosis factor alpha (TNF-α) and complement component 3 (C3) with AMD. Acadesine, an analog of AMP and an AMP-activated protein kinase (AMPK) activator, has been shown to have cytoprotective effects in human clinical trials as well as having anti-inflammatory and anti-vascular exudative effects in animals. The purpose of this study was to evaluate if acadesine is able to suppress TNF-α induced C3 in RPE cells. METHODS: ARPE-19 and human primary RPE cells were cultured and allowed to grow to confluence. TNF-α was used for C3 induction in the presence or absence of acadesine. Small molecule inhibitors and siRNA were used to determine if acadesine exerts its effect via the extracellular or intracellular pathway and to evaluate the importance of AMPK for these effects. The expression level of C3 was determined by immunoblot analysis. RESULTS: Acadesine suppresses TNF-α induced C3 in a dose dependent manner. When we utilized the adenosine receptor inhibitor dipyridamole (DPY) along with acadesine, acadesine{\textquoteright}s effects were abolished, indicating the necessity of acadesine to enter the cell in order to exert it{\textquoteright}s action. However, pretreatment with 5-iodotubericidin (5-Iodo), an adenosine kinase (AK) inhibitor, didn{\textquoteright}t prevent acadesine from decreasing TNF-α induced C3 expression suggesting that acadesine does not exert its effect through AMP conversion and subsequent activation of AMPK. Consistent with this, knockdown of AMPK α catalytic subunit did not affect the inhibitory effect of acadesine on TNF-α upregulation of C3. CONCLUSIONS: Our results suggest that acadesine suppresses TNF-α induced C3, likely through an AMPK-independent pathway, and could have potential use in complement over activation diseases.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0244307},
	author = {Efstathiou, Nikolaos E and Moustafa, Giannis A and Maidana, Daniel E and Konstantinou, Eleni K and Notomi, Shoji and Barbisan, Paulo R T and Georgakopoulos, Constantine D and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1309955,
	title = {Identification of a Novel TCF4 Isoform in the Human Corneal Endothelium},
	journal = {Cornea},
	volume = {37},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {899-903},
	abstract = {PURPOSE: Alternative splice isoforms of TCF4, a gene implicated in Fuchs corneal dystrophy, have been identified in multiple human tissues outside of the eye. The aim of this study was to identify the transcriptional profile of TCF4 in the corneal endothelium. METHODS: We extracted RNA from the donor corneal endothelium and performed rapid amplification of cDNA ends. We tested the expression pattern of 1 newly identified isoform (7b) in a panel of cDNA derived from multiple human tissues and included cDNA from corneal endothelial (CE) and retinal pigment epithelial cell lines. To further delineate differential expression of TCF4 splice variants that span CTG18.1, we analyzed expression of 6 alternative splice isoforms that are transcribed from either exon 2 or 3 in RNA extracted from the corneal endothelium of 3 normal donors and a CE cell line. RESULTS: We identified 11 different isoforms in control CE tissue, including 1 isoform (7b) not reported previously. This isoform is enriched specifically in the corneal endothelium and placenta compared with other tissues in a panel of human cDNA. CONCLUSIONS: We demonstrate the complex expression profile of TCF4 in the human corneal endothelium and reveal expression of alternative splice variants of TCF4.},
	keywords = {Aged, DNA, Complementary, Endothelium, Corneal, Female, Fuchs{\textquoteright} Endothelial Dystrophy, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Protein Isoforms, Transcription Factor 4, Trinucleotide Repeat Expansion},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001521},
	author = {Eghrari, Allen O and Vasanth, Shivakumar and Gapsis, Briana C and Bison, Henry and Jurkunas, Ula and Riazuddin, S Amer and Gottsch, John D}
}
@article {1573117,
	title = {Heterogeneity of eye drop use among symptomatic dry eye individuals in Japan: large-scale crowdsourced research using DryEyeRhythm application},
	journal = {Jpn J Ophthalmol},
	volume = {65},
	number = {2},
	year = {2021},
	month = {2021 Mar},
	pages = {271-281},
	abstract = {PURPOSE: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. STUDY DESIGN: Crowdsourced observational study. METHODS: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected included the type and frequency of eye drop use, demographics, medical history, lifestyle, and self-reported symptoms. Symptomatic DE was defined as an Ocular Surface Disease Index total score of >= 13. Risk factors for no eye drop use were identified using multivariate logistic regression analyses. RESULTS: Among 2619 individuals with symptomatic DE, 1876 did not use eye drops. The most common eye drop type was artificial tears (53.4\%), followed by hyaluronic acid 0.1\% (33.1\%) and diquafosol sodium 3\% (18.7\%). Risk factors (odds ratio [95\% confidence interval]) for no eye drop use were age (0.97 [0.97-0.98]), body mass index (1.04 [1.01-1.07]), brain disease (0.38 [0.15-0.98]), collagen disease (0.30 [0.13-0.68]), mental illness other than depression and schizophrenia (0.65 [0.45-0.93]), cataract surgery (0.12 [0.02-0.59]), ophthalmic surgery other than cataract and laser-assisted in situ keratomileusis (0.55 [0.34-0.88]), current (0.47 [0.38-0.57]) or past (0.58 [0.43-0.77]) contact lens use, \&gt;8\&nbsp;h screen exposure time (1.38 [1.05-1.81]), \&lt;6\&nbsp;h (1.24 [1.01-1.52]) and \&gt;9\&nbsp;h (1.34 [1.04-1.72]) sleep time, and water intake (0.97 [0.94-0.98]). CONCLUSION: Many participants with symptomatic DE did not use optimized eye drop treatment and identified risk factors for no eye drop use. The DryEyeRhythm application may help improve DE treatment.},
	issn = {1613-2246},
	doi = {10.1007/s10384-020-00798-1},
	author = {Eguchi, Atsuko and Inomata, Takenori and Nakamura, Masahiro and Nagino, Ken and Iwagami, Masao and Sung, Jaemyoung and Midorikawa-Inomata, Akie and Okumura, Yuichi and Fujio, Kenta and Fujimoto, Keiichi and Miura, Maria and Akasaki, Yasutsugu and Shokirova, Hurramhon and Hirosawa, Kunihiko and Kuwahara, Mizu and Zhu, Jun and Dana, Reza and Murakami, Akira and Kobayashi, Hiroyuki}
}
@article {1608577,
	title = {Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {129},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {88-99},
	abstract = {PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.07.009},
	author = {Ehlers, Justis P and Yeh, Steven and Maguire, Maureen G and Smith, Justine R and Mruthyunjaya, Prithvi and Jain, Nieraj and Kim, Leo A and Weng, Christina Y and Flaxel, Christina J and Schoenberger, Scott D and Kim, Stephen J}
}
@article {1363273,
	title = {CRB1: one gene, many phenotypes},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {397-405},
	abstract = {Mutations in the CRB1 gene cause severe retinal degenerations, which may present as Leber congenital amaurosis, early onset retinal dystrophy, retinitis pigmentosa, or cone-rod dystrophy. Some clinical features should alert the ophthalmologist to the possibility of CRB1 disease. These features are nummular pigmentation of the retina, atrophic macula, retinal degeneration associated with Coats disease, and a unique form of retinitis pigmentosa named para-arteriolar preservation of the retinal pigment epithelium (PPRPE). Retinal degenerations associated with nanophthalmos and hyperopia, or with keratoconus, can serve as further clinical cues to mutations in CRB1. Despite this, no clear genotype-phenotype relationship has been established in CRB1 disease. In CRB1-disease, as in other inherited retinal degenerations (IRDs), it is essential to diagnose the specific disease-causing gene for the disease as genetic therapy has progressed considerably in the last few years and might be applicable.},
	keywords = {Eye Proteins, Genetic Association Studies, Humans, Membrane Proteins, Nerve Tissue Proteins, Retinal Degeneration},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825277},
	author = {Ehrenberg, Miriam and Pierce, Eric A and Cox, Gerald F and Fulton, Anne B}
}
@article {1580484,
	title = {Genetic causes of nystagmus, foveal hypoplasia and subnormal visual acuity- other than albinism},
	journal = {Ophthalmic Genet},
	volume = {42},
	number = {3},
	year = {2021},
	month = {2021 Jun},
	pages = {243-251},
	abstract = {Background: To describe genetic molecular findings in individuals with congenital nystagmus, foveal hypoplasia, and subnormal vision, with normal ocular pigmentation (absence of diffuse transillumination or transparent retinal pigment typical for albinism).Methods: This is a retrospective, multicenter study of ophthalmic, systemic, and genetic features, as collected from medical records of patients diagnosed with infantile nystagmus and foveal hypoplasia. Ophthalmic findings include best-corrected visual acuity (BCVA), biomicroscopic examination, cycloplegic refraction, retinal examination, macular optical coherence tomography, and electroretinography. Genetic information was retrieved from the participating genetic clinics and included ethnicity and molecular diagnosis.Results: Thirty-one individuals met the inclusion criteria and had a secure molecular diagnosis. Mutations in two genes predominated, constituting 77.4\% of all the represented genes: SLC38A8 (45.1\%) and PAX6 (32.3\%). Seventy-eight percent of the subjects who had a measurable BCVA had moderate and severe visual impairment (range 20/80 to 20/270). Most patients with a mutation in SLC38A8 had mild to moderate astigmatism, while most patients with PAX6 mutation had moderate and severe myopia. Patients in the PAX6 group had variable degrees of anterior segment manifestations.Conclusion: In our cohort, the main causative genes for congenital nystagmus and foveal hypoplasia in normally pigmented eyes were SLC38A8 and PAX6. A mild phenotype in PAX6 mutations may be an under-diagnosed cause of nystagmus and foveal hypoplasia. Reaching an accurate genetic diagnosis is essential for both the patients and their family members. This enables predicting disease prognosis, tailoring correct follow-up, and providing genetic counseling and family planning to affected families.},
	issn = {1744-5094},
	doi = {10.1080/13816810.2021.1888128},
	author = {Ehrenberg, Miriam and Bagdonite-Bejarano, Laura and Fulton, Anne B and Orenstein, Naama and Yahalom, Claudia}
}
@article {1282111,
	title = {Case 38-2017. A 20-Year-Old Woman with Seizures and Progressive Dystonia},
	journal = {N Engl J Med},
	volume = {377},
	number = {24},
	year = {2017},
	month = {2017 Dec 14},
	pages = {2376-2385},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc1706109},
	author = {Eichler, Florian S and Swoboda, Kathryn J and Hunt, Ann L and Cestari, Dean M and Rapalino, Otto}
}
@article {669261,
	title = {The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016},
	pages = {22671},
	abstract = {Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin{\textquoteright}s potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated.},
	issn = {2045-2322},
	doi = {10.1038/srep22671},
	author = {Eidet, J R and Reppe, S and Pasovic, L and Olstad, O K and Lyberg, T and Khan, A Z and Fostad, I G and Chen, D F and Utheim, T P}
}
@article {1773511,
	title = {Comparing Outcomes of Phacoemulsification and Endocyclophotocoagulation with Either Dual Blade Goniotomy (PEcK) or Two Trabecular Stents (ICE2)},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {2879-2888},
	abstract = {PURPOSE: To compare outcomes of phacoemulsification and endocyclophotocoagulation with either dual blade goniotomy (PEcK) or two trabecular stents (ICE2). SETTING: Retrospective, nonrandomized comparative study from a level 3 triage center. METHODS: One hundred and seventy charts and a total of 1294 visits were reviewed following either PEcK or ICE2 from 2018 to 2022. One hundred and twenty-eight patients had PEcK and 42 underwent ICE2. Patients with less than 30 days of follow-up were excluded. The mean follow-up time was 505 {\textpm} 308 days. Two Kaplan-Meier curves (KM) assessed survival with <= baseline medications while maintaining (1) [GIC - Goal IOP Criteria] IOP <= goal IOP or (2) [PRC - Percent Reduction Criteria] IOP reduction >= 20\% with 5 mmHg <= IOP <= 21 mmHg for at least two consecutive visits. IOP and medication burden reduction were compared using a paired t-test. RESULTS: Most patients were Caucasian (65\%) and had mild-stage glaucoma (43\%). The most common glaucoma type was primary open-angle glaucoma (58\%). Average age was 72.2 years at the time of surgery.\&nbsp;Mean preoperative IOP was 17.58 {\textpm} 4.98 mmHg on 3.00 {\textpm} 1.41 medications in PEcK and 15.36 {\textpm} 3.58 mmHg on 1.81 {\textpm} 1.11 medications in ICE2 (p = 0.015 for IOP; p \&lt; 0.001 for medications). Under GIC, the success rate was significantly higher in PEcK at POM6 (69\% vs 46\%, p \&lt; 0.001) and POY1 (63\% vs 36\%, p \&lt; 0.001). Under PRC, the success rate was significantly higher in PEcK at POM6 (73\% vs 61\%, p = 0.031) and POY1 (67\% vs 50\%, p = 0.028). Mean reductions at POY1 were 5.00 {\textpm} 4.31 mmHg on 1.35 {\textpm} 1.08 less medications after PEcK and 3.14 {\textpm} 2.83 mmHg on 1.01 {\textpm} 0.94 less medications after ICE2 (p \&lt; 0.001 at POY1 for IOP; p \&lt; 0.05 after POW6 for medications). CONCLUSION: Both PEcK and ICE2 reduce medication and IOP from baseline, with PEcK having more favorable GIC and PRC success rates and greater IOP and medication reduction at 1 year.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S431356},
	author = {El Helwe, Hani and Oberfeld, Blake and Golsoorat Pahlaviani, Fatemeh and Falah, Henisk and Trzcinski, Jonathan and Sol{\'a}-Del Valle, David}
}
@article {1452975,
	title = {Development of the international orbital Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system},
	journal = {Int Forum Allergy Rhinol},
	volume = {9},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {804-812},
	abstract = {BACKGROUND: Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic-based staging system was developed. METHODS: An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed. RESULTS: Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3\% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0\% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty. CONCLUSION: Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high-quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH.},
	issn = {2042-6984},
	doi = {10.1002/alr.22316},
	author = {El Rassi, Edward and Adappa, Nithin D and Battaglia, Paolo and Castelnuovo, Paolo and Dallan, Iacopo and Freitag, Suzanne K and Gardner, Paul A and Lenzi, Ricardo and Lubbe, Darlene and Metson, Ralph and Moe, Kris S and Muscatello, Luca and Mustak, Hamzah and Nogueira, Jo{\~a}o Fl{\'a}vio and Palmer, James N and Prepageran, Narayanan and Ramakirshnan, Vijay R and Sacks, Raymond and Snyderman, Carl H and Stefko, S Tonya and Turri-Zanoni, Mario and Wang, Eric W and Zhou, Bing and Bleier, Benjamin S}
}
@article {1629464,
	title = {Suppression of lipopolysaccharide-induced corneal opacity by hepatocyte growth factor},
	journal = {Sci Rep},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 Jan 11},
	pages = {494},
	abstract = {Keratitis induced by bacterial toxins, including lipopolysaccharide (LPS), is a major cause of corneal opacity and vision loss. Our previous study demonstrates hepatocyte growth factor (HGF) promotes epithelial wound healing following mechanical corneal injury. Here, we investigated whether HGF has the capacity to suppress infectious inflammatory corneal opacity using a new model of LPS-induced keratitis. Keratitis, induced by two intrastromal injections of LPS on day 1 and 4 in C57BL/6 mice, resulted in significant corneal opacity for up to day 10. Following keratitis induction, corneas were topically treated with 0.1\% HGF or PBS thrice daily for 5\&nbsp;days. HGF-treated mice showed a significantly smaller area of corneal opacity compared to PBS-treated mice, thus improving corneal transparency. Moreover, HGF treatment resulted in suppression of α-SMA expression, compared to PBS treatment. HGF-treated corneas showed normalized corneal structure and reduced expression of pro-inflammatory cytokine, demonstrating that HGF restores corneal architecture and immune quiescence in corneas with LPS-induced keratitis. These findings offer novel insight into the potential application of HGF-based therapies for the prevention and treatment of infection-induced corneal opacity.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-04418-x},
	author = {Elbasiony, Elsayed and Cho, Wonkyung and Mittal, Sharad K and Chauhan, Sunil K}
}
@article {1667721,
	title = {Increased activity of lacrimal gland mast cells are associated with corneal epitheliopathy in aged mice},
	journal = {NPJ Aging},
	volume = {9},
	number = {1},
	year = {2023},
	month = {2023 Feb 27},
	pages = {2},
	abstract = {The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.},
	issn = {2731-6068},
	doi = {10.1038/s41514-023-00099-0},
	author = {Elbasiony, Elsayed and Cho, WonKyung J and Singh, Aastha and Mittal, Sharad K and Zoukhri, Driss and Chauhan, Sunil K}
}
@article {1806651,
	title = {Re: Kianian et al.: Enhancing the assessment of large language models in medical information generation (Ophthalmol Retina. 2024;8:195-201)},
	journal = {Ophthalmol Retina},
	year = {2024},
	month = {2024 Feb 16},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2024.01.009},
	author = {Eleiwa, Taher K and Elhusseiny, Abdelrahman M}
}
@article {1615222,
	title = {Adverse Ocular Events following COVID-19 Vaccination},
	journal = {Inflamm Res},
	volume = {70},
	number = {10-12},
	year = {2021},
	month = {2021 Dec},
	pages = {1005-1009},
	keywords = {2019-nCoV Vaccine mRNA-1273, Adult, Aged, Aged, 80 and over, BNT162 Vaccine, ChAdOx1 nCoV-19, COVID-19 Vaccines, Eye, Female, Humans, Inflammation, Male, Middle Aged, SARS-CoV-2, Vaccination, Vision, Ocular, Young Adult},
	issn = {1420-908X},
	doi = {10.1007/s00011-021-01506-6},
	author = {Eleiwa, Taher K and Gaier, Eric D and Haseeb, Abid and ElSheikh, Reem H and Sallam, Ahmed B and Elhusseiny, Abdelrahman M}
}
@article {1589767,
	title = {Early Experience With Ahmed Clear Path Glaucoma Drainage Device in Childhood Glaucoma},
	journal = {J Glaucoma},
	volume = {30},
	number = {7},
	year = {2021},
	month = {2021 Jul 01},
	pages = {575-578},
	abstract = {PURPOSE: The aim was to evaluate the short-term outcomes of Ahmed clear path (ACP) valveless glaucoma drainage device in childhood glaucoma. METHODS: Retrospective chart review of all patients 16 years or below with childhood glaucoma who had ACP implantation at Boston Children{\textquoteright}s Hospital from December 2019 to June 2020 with at least 6 months follow-up period. RESULTS: The study included 7 eyes of 5 patients implanted by a single surgeon. The median follow-up was 12 months. The mean intraocular pressure (IOP) was reduced from 36{\textpm}3.5 mm Hg on a mean of 2.7{\textpm}0.6 glaucoma medications preoperatively to a mean IOP of 12.4{\textpm}2.8 mm Hg (P\&lt;0.001) on a mean of 0.7{\textpm}0.8 medications postoperatively at final follow-up (P=0.0009). Complete success was achieved in 4 eyes while qualified success was achieved in 3 eyes. CONCLUSION: The ACP glaucoma drainage device provided good short-term IOP control and technical advantages for implantation for pediatric eyes were observed.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001855},
	author = {Elhusseiny, Abdelrahman M and VanderVeen, Deborah K}
}
@article {1789146,
	title = {Correlation of Strabismus Surgical Outcomes Graded by Goal-Determined Metric with Patient Satisfaction Survey},
	journal = {Am J Ophthalmol},
	year = {2023},
	month = {2023 Dec 15},
	abstract = {PURPOSE: While strabismus surgery outcomes can be objectively measured, patient perception of results may differ. We present surgical outcomes graded by a prospective, "goal-determined metric" and compare these outcomes to results of a patient satisfaction survey. DESIGN: Validity analysis comparing a clinical "goal-determined metric" to patient satisfaction METHODS: Goal-determined metric outcomes (2018-2021) for two surgeons treating esotropia or exotropia for diplopia control or reconstructive goals were collected. Inclusion required complete post-operative examination 2-6 months after surgery and a satisfaction survey. RESULTS: Record review identified 275 patients; 228 (median age 41 years (IQR 13-59)) met inclusion criteria. For the entire cohort, 87\% were graded as "excellent" outcomes, and 78\% of patients were overall "very satisfied". Agreement between patients{\textquoteright} and surgeons{\textquoteright} grading was 75-79\% for all reconstructive surgery and for treatment of diplopia from esotropia. Agreement was lower, though not statistically different, for treatment of diplopia from exotropia (64\%; 95\% CI 43-80\%) (P=0.184). Pre-operative risk factors, concurrent vertical or oblique surgery, and sex did not affect outcomes or satisfaction. Performance of activities requiring distance viewing improved more than performance of activities at near after esotropia-diplopia surgery (odds ratio 3.0 (95\% CI: 1.5-6.4, P=0.004)). For reconstructive cases achieving "much better" eye alignment, 62\% and 72\% (previously esotropic and exotropic) reported enhanced self-confidence. CONCLUSIONS: Outcomes graded by goal-determined metric correlated well with many aspects of patient satisfaction. Patient-perceived improvement in appearance was important regardless of goal. Greater improvement in performance of activities requiring distance rather than near viewing characterized treatment of diplopia from esotropia.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.12.007},
	author = {Elhusseiny, Abdelrahman M and Agrawal, Surya and Staffa, Steven J and Zurakowski, David and Hunter, David G and Dagi, Linda R}
}
@article {1608586,
	title = {Relationship between screen time and dry eye symptoms in pediatric population during the COVID-19 pandemic},
	journal = {Ocul Surf},
	volume = {22},
	year = {2021},
	month = {2021 Aug 05},
	pages = {117-119},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.08.002},
	author = {Elhusseiny, Abdelrahman M and Eleiwa, Taher K and Yacoub, Magdi S and George, Joseph and ElSheikh, Reem H and Haseeb, Abid and Kwan, James and Elsaadani, Ibrahim A and Abo Shanab, Sheren M and Solyman, Omar and Saeed, Hajirah N}
}
@article {1709696,
	title = {Association of Neighborhood Environment with the Outcomes of Childhood Glaucoma},
	journal = {Ophthalmol Glaucoma},
	volume = {6},
	number = {6},
	year = {2023},
	month = {2023 Nov-Dec},
	pages = {636-641},
	abstract = {PURPOSE: To determine the association between different neighborhood environment factors and the outcomes of childhood glaucoma. DESIGN: A retrospective cohort. PARTICIPANTS: Childhood glaucoma patients <= 18 years of age at the time of diagnosis. METHODS: A retrospective chart review of childhood glaucoma patients who presented to Boston Children{\textquoteright}s Hospital between 2014 and 2019. Data collected included etiology, intraocular pressure (IOP), management, and visual outcomes. Child Opportunity Index (COI) was used as a metric of neighborhood quality. MAIN OUTCOMES MEASURES: The association of visual acuity (VA) and IOP with COI scores using linear mixed-effect models, adjusting for individual demographics. RESULTS: A total of 221 eyes (149 patients) were included. Of these, 54.36\% were male and 56.4\% were non-Hispanic Whites. The median age at the time of presentation was 5 months for primary glaucoma and 5 years for secondary glaucoma. The median age at the last follow-up was 6 and 13 years for primary and secondary glaucoma, respectively. A chi-square test revealed that the COI, health and environment, social and economic, and education indexes between primary and secondary glaucoma patients were comparable. For primary glaucoma, the overall COI and a higher education index were associated with a lower final IOP (P\&nbsp;\&lt;\&nbsp;0.05), and higher education index was associated with a lower number of glaucoma medications at the last follow-up (P\&nbsp;\&lt;\&nbsp;0.05). For secondary glaucoma, higher overall COI, health and environment, social and economic, and education indices were associated with better final VA (lower logarithms of the minimum angle of resolution VA) (P\&nbsp;\&lt;\&nbsp;0.001). CONCLUSIONS: Neighborhood environment quality is a potentially important variable for predicting outcomes in childhood glaucoma. Lower COI scores were associated with worse outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Child, Female, Glaucoma, Humans, Hydrophthalmos, Intraocular Pressure, Male, Neighborhood Characteristics, Retrospective Studies},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2023.06.001},
	author = {Elhusseiny, Abdelrahman M and Oke, Isdin and Adomfeh, Jean and Chauhan, Muhammad Z and VanderVeen, Deborah K}
}
@article {1598070,
	title = {Optical coherence tomography in the setting of optic nerve head cupping reversal in secondary childhood glaucoma},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Jun 02},
	abstract = {Reversal of optic nerve head (ONH) cupping has been considered an important clinical observation that signals surgical success and control of intraocular pressure (IOP) in childhood glaucoma. Many theories based on elasticity of pediatric eyes have been proposed, including anterior movement of the elastic lamina cribrosa or shrinkage of the scleral canal. The relationship between these factors and axonal loss is unclear when reversal of cupping has been observed. Retinal nerve fiber layer (RNFL) optical coherence tomography (OCT) can help to clarify this. We present a case series of 4 pediatric patients with secondary glaucoma that demonstrated ONH cupping reversal with pre- and postoperative clinical images and RNFL OCT.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2021.03.003},
	author = {Elhusseiny, Abdelrahman M and VanderVeen, Deborah K}
}
@article {1532349,
	title = {Self-grading effect of inferior oblique myectomy and recession},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Sep 02},
	abstract = {PURPOSE: To evaluate the outcomes of inferior oblique (IO) weakening surgery, whether recession or myectomy, and to assess the dose-response relationship and correlation with angle of preoperative hypertropia. METHODS: The medical records of all patients with vertical deviation in primary gaze who underwent unilateral IO-weakening surgery, either recession or myectomy, at Boston Children{\textquoteright}s Hospital over an 8-year period with a minimum postoperative follow-up of 1 month were reviewed retrospectively. Outcome measures were effect of IO weakening surgery on vertical deviation in primary gaze and its correlation with the preoperative angle of hyperdeviation. Secondary outcomes included resolution of abnormal head posture, reduction of ocular torsion, and postoperative under- and overcorrection RESULTS: A total of 94 patients were identified (mean age at surgery, 29.3 {\textpm} 19.8 years; range, 1-69). The mean postoperative follow-up period was 17.2 {\textpm} 15 months. IO recession was performed in 30 patients; IO myectomy, in 64. Surgical success in primary position was achieved in 72 patients (77\%), with resolution of anomalous preoperative head posture in 93\%. The mean effect on alignment in primary position was 11.3 {\textpm} 6.8. The response to IO-weakening surgery was strongly correlated with the preoperative hyperdeviation for both recession (R = 0.53) and myectomy (R = 0.87). CONCLUSIONS: As with other types of strabismus surgery, IO weakening has a "self-grading" contribution, in which the surgical effect strongly correlates with the magnitude of preoperative deviation. A large range of vertical misalignment can be corrected with the same surgical approach.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.04.014},
	author = {Elhusseiny, Abdelrahman M and Gore, Charlotte and Sadiq, Mohammad Ali A and Dagi, Linda R and Kazlas, Melanie and Hunter, David G}
}
@article {1517210,
	title = {Outcomes of Glaucoma Drainage Devices in Childhood Glaucoma},
	journal = {Semin Ophthalmol},
	year = {2020},
	month = {2020 Jun 20},
	pages = {1-11},
	abstract = {PURPOSE: Angle surgery is the gold standard for the management of many types of childhood glaucoma, yet glaucoma drainage devices (GDD) are effective tools for refractory advanced cases or secondary childhood glaucomas. The purpose of this article is to review recently published literature focused on the use of GDDs for pediatric glaucoma, including GDD general principles and surgical outcomes. METHODS: Literature review of various electronic databases was performed. RESULTS: 71 papers were reviewed for outcomes of GDD in childhood glaucomas. Success rates were usually defined by intraocular pressure (IOP) of 5-22\&nbsp;mmHg, with or without medications. Success rates were typically higher for non-valved GDDs but varied by length of follow-up. Non-valved GDDs afford lower and longer-lasting IOP control in pediatric eyes than valved GDD, however, no randomized controlled trials exist in childhood glaucoma. CONCLUSION: Various designs of GDDs are available for management of childhood glaucoma with good short-term success rates; individual patient factors should be taken into consideration when selecting a specific device.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1781906},
	author = {Elhusseiny, Abdelrahman M and VanderVeen, Deborah K}
}
@article {1798331,
	title = {Re: Sawyer et al.: Diagnostic role of oral fluorescein angiography in pediatric ambulatory clinics (Ophthalmol Retina. 2024;8:204-206)},
	journal = {Ophthalmol Retina},
	volume = {8},
	number = {3},
	year = {2024},
	month = {2024 Mar},
	pages = {e6-e7},
	keywords = {Child, Fluorescein Angiography, Humans, Retina},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.11.019},
	author = {Elhusseiny, Abdelrahman M and Grigorian, Florin and Sallam, Ahmed B}
}
@article {1635654,
	title = {Corneal opacification in Sanjad-Sakati syndrome},
	journal = {Am J Ophthalmol Case Rep},
	volume = {26},
	year = {2022},
	month = {2022 Jun},
	pages = {101503},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101503},
	author = {Elhusseiny, Abdelrahman M and Saeed, Hajirah N}
}
@article {1638555,
	title = {Topical cenegermin 0.002\% for pediatric neurotrophic keratopathy},
	journal = {Eur J Ophthalmol},
	volume = {32},
	number = {6},
	year = {2022},
	month = {2022 Nov},
	pages = {3420-3424},
	abstract = {PURPOSE: To evaluate the efficacy and safety of cenegermin 0.002\% ophthalmic drops in the management of pediatric neurotrophic keratopathy (NK). METHODS: Retrospective chart review of children under the age of 18 years diagnosed with NK at Boston Children{\textquoteright}s Hospital/Massachusetts Eye and Ear Infirmary and treated with topical cenegermin 0.002\% ophthalmic solution between June 2018 and June 2021 was performed. Data collection included etiology of NK, age at time of initiation of topical cenegermin, laterality, ethnicity, gender, history of previous ocular therapy, pre- and post-therapy best corrected visual acuity, pre- and post-therapy cornea examination, any adverse events from topical cenegermin, associated ocular conditions, and history of ocular surgeries. RESULTS: The current study includes four eyes of four pediatric patients with a mean age of 4.5 {\textpm} 2.0 years at the time of initiation of topical cenegermin therapy. The mean time from NK diagnosis until start of topical cenegermin drops was 5.2 {\textpm} 4.3 months and mean follow-up time was 15 {\textpm} 9.6 months. In all four patients, marked improvement in epitheliopathy was demonstrated after completion of therapy. Best corrected visual acuity was measurable in 3 eyes of 3 patients, and it improved from a mean of 0.07 {\textpm} 0.01 to a mean of 0.29 {\textpm} 0.26 (P = 0.3). No adverse events related to cenegermin therapy were noted. CONCLUSION: Topical cenegermin was effective in improving corneal healing for pediatric NK.},
	keywords = {Adolescent, Child, Child, Preschool, Cornea, Corneal Dystrophies, Hereditary, Humans, Keratitis, Nerve Growth Factor, Ophthalmic Solutions, Recombinant Proteins, Retrospective Studies, Trigeminal Nerve Diseases},
	issn = {1724-6016},
	doi = {10.1177/11206721221094783},
	author = {Elhusseiny, Abdelrahman M and Traish, Aisha S and Saeed, Hajirah N and Mantagos, Iason S}
}
@article {1817271,
	title = {Bevacizumab as adjunctive therapy in anterior persistent fetal vasculature},
	journal = {Eur J Ophthalmol},
	volume = {34},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {NP18-NP21},
	abstract = {PURPOSE: Surgical removal of a vascularized pupillary membrane may be challenging with the risk of intraoperative bleeding and postoperative recurrence. We present a case of a 4-week-old who presented with anterior persistent fetal vasculature (PFV) and dense vascularized pupillary membrane in which the use of intracameral and intravitreal bevacizumab may have contributed to successful treatment.

OBSERVATION: A 4-week-old-month-old otherwise healthy girl was referred to Boston Children{\textquoteright}s Hospital for evaluation of cataract. Ocular examination revealed right microcornea and vascularized pupillary membrane. The left eye exam was unremarkable. Only three weeks after surgical excision of the pupillary membrane and cataract extraction, recurrence of a vascular pupillary membrane was noted. Repeat membranectomy with pupilloplasty and use of intracameral bevacizumab was performed. The pupillary opening was further opened 5 months later, after repeat (intravitreal) bevacizumab, and the pupil has remained open and stable with \&gt;6 months{\textquoteright} follow-up.

CONCLUSION AND IMPORTANCE: This case suggests a role for bevacizumab in the management of PFV, however, a cause-and-effect relationship cannot be proven. Further prospective comparative studies are needed to confirm our findings.},
	keywords = {Bevacizumab, Cataract, Cataract Extraction, Child, Eye Abnormalities, Female, Humans, Infant, Newborn, Persistent Hyperplastic Primary Vitreous},
	issn = {1724-6016},
	doi = {10.1177/11206721231187428},
	author = {Elhusseiny, Abdelrahman M and Hennein, Lauren and VanderVeen, Deborah K}
}
@article {1655709,
	title = {Topical netarsudil 0.02\% as adjunctive therapy in refractory pediatric glaucoma},
	journal = {J AAPOS},
	volume = {26},
	number = {6},
	year = {2022},
	month = {2022 Dec},
	pages = {300.e1-300.e5},
	abstract = {PURPOSE: To evaluate the efficacy of topical netarsudil 0.02\% as adjunctive therapy in children with refractory pediatric glaucoma. METHODS: The medical records of patients <=18 years diagnosed with pediatric glaucoma treated with topical netarsudil 0.02\% from June 2019 to March 2022 were reviewed retrospectively. Data collected included age, sex, ethnicity, etiology of glaucoma, history of previous or subsequent glaucoma surgery, and intraocular pressure (IOP) before and after the addition of topical netarsudil. RESULTS: A total of 21 eyes of 16 patients (11 males) were included. Five patients used topical netarsudil in both eyes. Eight patients were Hispanic. The mean number of glaucoma surgeries and medications before initiating topical netarsudil was 1.8 {\textpm} 1.2 and 3.7 {\textpm} 0.5, respectively. The mean age prior to starting topical netarsudil was 8.9 {\textpm} 4.1 years. The mean follow-up after initiating topical netarsudil was 11.3 {\textpm} 8.2 months. The IOP was significantly reduced from 26.3 {\textpm} 6.2 mm Hg before topical netarsudil to 19.6 {\textpm} 6.02 mm Hg at 1 month in 15 eyes (P \&lt; 0.01), 18.2 {\textpm} 6.9 mm Hg at 3-months in 18 eyes (P \&lt; 0.01), 18.3 {\textpm} 7.3 mm Hg at 6 months in 13 eyes (P = 0.01), 17.6 {\textpm} 5.07 mm Hg at 9 months in 14 eyes (P = 0.002), and 17.4 {\textpm} 3.1 mm Hg at 12 months in 13 eyes (P = 0.002). Nine eyes (43\%) underwent additional glaucoma surgery due to long-term failure of topical netarsudil to reduce IOP despite an initial reduction, and one eye had persistent IOP elevation >=21 mm Hg despite the addition of topical netarsudil. CONCLUSIONS: In our small cohort of patients with refractory pediatric glaucoma, the addition of topical netarsudil reduced IOP, potentially delaying the need for surgery.},
	keywords = {Adolescent, Child, Child, Preschool, Glaucoma, Humans, Intraocular Pressure, Male, Retrospective Studies, Tonometry, Ocular, Treatment Outcome},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.08.526},
	author = {Elhusseiny, Abdelrahman M and Abbasian, Javaneh}
}
@article {1598061,
	title = {A novel variant in the TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy},
	journal = {Eur J Ophthalmol},
	volume = {32},
	number = {6},
	year = {2022},
	month = {2022 Nov},
	pages = {NP6-NP9},
	abstract = {PURPOSE: To report a case of 16-month-old boy with a novel variant TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy. OBSERVATION: A 16-month-old otherwise healthy boy was referred to Boston Children{\textquoteright}s Hospital for evaluation of strabismus. Ocular examination revealed intermittent esotropia, left hypotropia, and limited left eye elevation in both adduction and abduction. Full cycloplegic hyperopic correction of +3.50 diopters (D) over both eyes was given to the patient. Over several months, refraction of the right eye showed progressive myopia (-6.00 D) with new onset iris heterochromia. Fundus examination showed there was a large area of chorioretinal atrophy with abrupt ending of the blood vessels; anterior to the ora serrata there were diffuse vitreous bands and veils that reached the lens anteriorly in direct contact with the lenticular opacity. A novel heterozygous nonsense likely pathogenic variant was identified in the TSPAN12 gene (NM_012338.3) c.315T\&gt;A (p.Cys105Ter) confirming the diagnosis of FEVR. CONCLUSION AND IMPORTANCE: Asymmetric FEVR rarely present with unilateral axial myopia however association with acquired heterochromia and cataract has never been reported. We report a case of FEVR caused by a novel TSPAN12 likely pathogenic nonsense variant presenting as unilateral progressive myopia, acquired heterochromia, and pediatric cataract.},
	keywords = {Cataract, Child, DNA Mutational Analysis, Eye Diseases, Hereditary, Familial Exudative Vitreoretinopathies, Humans, Infant, Male, Mutation, Mydriatics, Myopia, Degenerative, Pedigree, Retina, Retinal Diseases, Tetraspanins},
	issn = {1724-6016},
	doi = {10.1177/11206721211027415},
	author = {Elhusseiny, Abdelrahman M and Jabroun, Mireille and Rajabi, Farrah and Gonzalez, Efren and Alkharashi, Maan}
}
@article {1522738,
	title = {Acute, severe dystonia after strabismus surgery in a patient on propofol, ondansetron, and bupropion},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Jul 18},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.05.006},
	author = {Elhusseiny, Abdelrahman M and Grush, Artem and Dagi, Linda R}
}
@article {1645462,
	title = {Posterior Polymorphous Corneal Dystrophy in a Pediatric Population},
	journal = {Cornea},
	volume = {41},
	number = {6},
	year = {2022},
	month = {2022 Jun 01},
	pages = {734-739},
	abstract = {PURPOSE: The aim of this study was to evaluate the clinical and topographic features of posterior polymorphous corneal dystrophy (PPCD) in children aged 15 years or younger with a long-term follow-up. Retrospective case series. METHODS: A retrospective chart review of patients who were diagnosed with PPCD at Boston Children{\textquoteright}s Hospital from 1999 to 2020 was performed. Data collected included age at the time of diagnosis, slit lamp findings, cycloplegic refraction, best-corrected visual acuity, central corneal thickness, specular microscopy, and corneal topography findings whenever available. RESULTS: Twenty-seven eyes of 19 patients were included (11 unilateral and 8 bilateral cases). Ten patients were girls (52.6\%). Left eye was affected in 14 eyes. The mean age at the time of diagnosis was 8.5 {\textpm} 3.3 years, with a mean follow-up of 5.3 years. In unilateral cases, there was a statistically significant difference in the endothelial cell density (P = 0.01), coefficient variation (P = 0.03), and hexagonality (P = 0.01) between the affected and the contralateral unaffected eyes. The mean best-corrected visual acuity at initial presentation was 0.8 {\textpm} 0.2 compared with 0.9 {\textpm} 0.08 in unaffected eyes (P = 0.04). The mean astigmatism was higher in the affected eye (+1.7 diopters) compared with (+1.00) the unaffected eye (P = 0.07). At initial presentation, 7 of 27 eyes had amblyopia, which resolved, either partially or completely, in 5 eyes after treatment. CONCLUSIONS: PPCD can present early in children with astigmatism and anisometropic amblyopia. A careful slit lamp examination for children presenting with anisoastigmatism is necessary to diagnose PPCD. Contrary to adults, presentation is often unilateral. Such patients should be followed up regularly with cycloplegic retinoscopy to prevent and treat refractive amblyopia if present.},
	keywords = {Adult, Amblyopia, Astigmatism, Child, Cornea, Corneal Dystrophies, Hereditary, Corneal Topography, Female, Humans, Male, Mydriatics, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002847},
	author = {Elhusseiny, Abdelrahman M and Saeed, Hajirah N}
}
@article {1517169,
	title = {Collector Channels: Role and Evaluation in Schlemm{\textquoteright}s Canal Surgery},
	journal = {Curr Eye Res},
	volume = {45},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {1181-1187},
	abstract = {OBJECTIVES: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. RESULTS: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm{\textquoteright}s canal-based surgeries, collector channel{\textquoteright}s patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. CONCLUSIONS: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2020.1773866},
	author = {Elhusseiny, Abdelrahman M and Jamerson, Emery C and Menshawey, Rahma and Tam, Emily K and El Sayed, Yasmine M}
}
@article {1817321,
	title = {Isolated eyelid neonatal Langerhans cell histiocytosis},
	journal = {Orbit},
	year = {2024},
	month = {2024 Jan 30},
	pages = {1-5},
	abstract = {Langerhans cell histiocytosis (LCH) is a condition characterized by clonal proliferation of the phagocytic cells derived from the bone marrow. In this article, we present an exceedingly rare case of congenital/neonatal LCH in a 3-week-old girl who initially presented with an isolated swelling of the eyelid, initially misdiagnosed as a chalazion. Subsequently, a biopsy was performed, and histopathological evaluation confirmed the diagnosis of LCH. A staging work-up revealed no evidence of multisystem involvement, and thus, local steroid injection was performed as the initial treatment for the residual lesion. Cases of localized LCH that manifest as eyelid masses are rare, and most reported cases involve children over the age of one year. To the best of our knowledge, this case represents the first reported instance of neonatal LCH presenting as an eyelid mass. Although neonatal LCH is rare, ophthalmologists must be aware of this presentation and include it in the differential diagnosis for eyelid lesions in infants during the first month of life.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2023.2300802},
	author = {Elhusseiny, Abdelrahman M and Azhari, Jamal O and Kornhauser, Tom and Kilgore, David A and Wilson, David K and Bielamowicz, Kevin J and Stallings-Archer, Kandi A and Pemberton, John D}
}
@article {1517205,
	title = {Trochleitis presenting with double vision in a patient with juvenile idiopathic arthritis},
	journal = {Orbit},
	volume = {40},
	number = {4},
	year = {2021},
	month = {2021 Aug},
	pages = {342-343},
	issn = {1744-5108},
	doi = {10.1080/01676830.2020.1772317},
	author = {Elhusseiny, Abdelrahman M and Gise, Ryan and Mantagos, Iason S}
}
@article {1586185,
	title = {Long-term ophthalmic outcomes in 120 children with unilateral coronal synostosis: a 20-year retrospective analysis},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Mar 11},
	abstract = {BACKGROUND: Prior studies comparing ophthalmic outcomes after treating unicoronal synostosis (UCS) by early endoscopic strip craniectomy (ESC) versus later fronto-orbital advancement (FOA) are modest in sample size, or lack consistent age adjustment. We report long-term, age-adjusted ophthalmic outcomes for a large cohort after nonrandomized treatment by one of these two options. METHODS: The following data was retrieved from a retrospective review of the medical records of patients with treated UCS born since 2000: cycloplegic refractions, sensorimotor examinations, and strabismus procedures before craniofacial repair and postoperatively at approximately 18 and 60 months of age. V-pattern strabismus was graded as mild (absent or + 1/-1 oblique dysfunction) versus moderate-to-severe (>=+2/-2 oblique dysfunction or left to right vertical alignment change of >=20Δ or ocular torticollis \&gt;15{\textdegree}). RESULTS: A total of 120 infants were included: 60 treated by FOA and 60 by ESC. By the late examination, aniso-astigmatism was present in 71.8\% of FOA-treated patients and 46\% of ESC-treated patients (P \&lt; 0.0001). By late examination, the age-adjusted odds ratio of moderate-to-severe V-pattern strabismus after treatment by FOA versus ESC was 2.65 (95\% CI, 1.37-6.28; P = 0.02); strabismus surgery was performed in 26 infants treated by FOA compared with 13 treated by ESC (OR = 2.8; P = 0.02). Amblyopia developed in 60\% of FOA-treated patients compared with 35\% of those treated by ESC (OR 3.0; 95\% CI, 1.3-6.7; P = 0.02). CONCLUSIONS: Our age-adjusted ophthalmic results confirm better long-term outcomes after treatment of USC by endoscopic strip craniectomy. Recognition and referral of affected infants by the earliest months of life facilitates the opportunity for endoscopic repair.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.10.013},
	author = {Elhusseiny, Abdelrahman M and MacKinnon, Sarah and Zurakowski, David and Huynh, Elisah and Dagi, Linda R}
}
@article {1789076,
	title = {Quality, reliability, technical quality, and readability of online information on pediatric cataract},
	journal = {J Cataract Refract Surg},
	volume = {49},
	number = {12},
	year = {2023},
	month = {2023 Dec 01},
	pages = {1283-1284},
	keywords = {Child, Comprehension, Humans, Reproducibility of Results},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000001283},
	author = {Elhusseiny, Abdelrahman M and Hassan, Amr K and Hassan, Mohamed A and Abdelnaem, Salah and Sallam, Ahmed B}
}
@article {1478327,
	title = {Evaluation and Management of V pattern Strabismus in Craniosynostosis},
	journal = {J Binocul Vis Ocul Motil},
	year = {2019},
	month = {2019 Dec 19},
	pages = {1-6},
	abstract = {V pattern strabismus is the most common ocular motor disorder reported in patients with craniosynostosis. Strabismus management may prove challenging, and few studies provide perspective on surgical approach. The purpose of this review is to discuss evaluation and surgical options for treating V pattern strabismus in patients with craniosynostosis. We provide a step-by-step approach to facilitate surgical planning.},
	issn = {2576-1218},
	doi = {10.1080/2576117X.2019.1693822},
	author = {Elhusseiny, Abdelrahman M and Huynh, Elisah M and Dagi, Linda R}
}
@article {1483600,
	title = {Severe reverse amblyopia with atropine penalization},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Jan 14},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.12.001},
	author = {Elhusseiny, Abdelrahman M and Wu, Carolyn and MacKinnon, Sarah and Hunter, David G}
}
@article {1603861,
	title = {Virtual reality prototype for binocular therapy in older children and adults with amblyopia},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Jul 08},
	abstract = {PURPOSE: To evaluate the best-corrected visual acuity and stereoacuity gains in children \&gt;7 years of age and adults with unilateral amblyopia treated with a prototype virtual reality-based binocular amblyopia therapy. METHODS: In this randomized, double masked, cross-in clinical trial, patients at Boston Children{\textquoteright}s Hospital with unilateral anisometropic and/or strabismic amblyopia and history of prior amblyopia treatment failure were randomized to either a full-treatment group (8 weeks of binocular treatment using therapeutic software application in virtual reality headset) or a sham-crossover group (4 weeks of sham treatment followed by 4 weeks of binocular treatment). Amblyopic eye visual acuity and stereoacuity were evaluated at 4, 8, and 16 weeks{\textquoteright} follow-up. RESULTS: The study cohort included 20 participants (10 females), with a median age of 9 years (range, 7-38 years). In the full-treatment group (11 patients), the mean amblyopic eye logMAR visual acuity at 16 weeks was 0.49 {\textpm} 0.26, compared with 0.47 {\textpm} 0.20 at baseline. In the sham-crossover group, it was 0.51 {\textpm} 0.18 at 16 weeks, compared with 0.53 {\textpm} 0.21 at baseline. Stereoacuity (log arcsec) was significantly improved, from 7.3 {\textpm} 2 at baseline to 6.6 {\textpm} 2.3 at 8 weeks (P \&lt; 0.001) and 6.7 {\textpm} 2.6 at 16 weeks (P \&lt; 0.001). No significant adverse events (diplopia, asthenopia, or worsening strabismus) were noted in either group. CONCLUSIONS: Although the virtual reality-based prototype for binocular amblyopia therapy did not significantly improve visual acuity in the amblyopic eyes of older children and adults, stereoacuity did significantly improve compared with baseline; improvements were clinically minute. However, larger studies are required to confirm the results.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2021.03.008},
	author = {Elhusseiny, Abdelrahman M and Bishop, Kaila and Staffa, Steven J and Zurakowski, David and Hunter, David G and Mantagos, Iason S}
}
@article {1732711,
	title = {Early Experience with the Paul Glaucoma Implant in Childhood Glaucoma: A Case Series},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {1939-1944},
	abstract = {PURPOSE: The Paul glaucoma implant (PGI, Advanced Ophthalmic Innovations, Singapore, Republic of Singapore) is a recently developed novel non-valved glaucoma drainage device (GDD) designed to effectively reduce the intraocular pressure (IOP) in glaucoma patients with a theoretically reduced risk of postoperative complications such as hypotony, endothelial cell loss, strabismus, and diplopia. Limited literature has evaluated its use in adult glaucoma; however, its use in pediatric glaucoma has not been reported to date. We present our early experience with PGI in refractory childhood glaucoma. PATIENTS AND METHODS: This study was retrospective single-surgeon case series in a single tertiary center. RESULTS: Three eyes of 3 patients with childhood glaucoma were enrolled in the study. During nine months of follow-up, postoperative IOP and number of glaucoma medications were significantly lower than preoperative values in all the enrolled patients. None of the patients developed postoperative complications including postoperative hypotony, choroidal detachment, endophthalmitis, or corneal decompensation. CONCLUSION: PGI is an efficient and relatively safe surgical treatment option in patients with refractory childhood glaucoma. Further studies with larger number of participants and longer follow-up period are required to confirm our encouraging results.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S414183},
	author = {Elhusseiny, Abdelrahman M and Khodeiry, Mohamed M and Lee, Richard K and Shaarawy, Tarek and Waqar, Salman and Sayed, Mohamed S}
}
@article {1664946,
	title = {Cataract surgery in myopic eyes},
	journal = {Curr Opin Ophthalmol},
	volume = {34},
	number = {1},
	year = {2023},
	month = {2023 Jan 01},
	pages = {64-70},
	abstract = {PURPOSE OF REVIEW: We discuss the preoperative, intraoperative, and postoperative considerations for cataract surgery in eyes with high myopia. We also reviewed the recent literature on refractive outcomes and complications of cataract surgery in myopic eyes. RECENT FINDINGS: Several novel intraocular lens (IOL) power calculation formulas have recently been developed to optimize refractive outcomes. Haigis formula is the most accurate among the third-generation IOL formulas. Novel formulas such as Barrett Universal II, Kane, and modified Wang-Koch adjustment for Holladay I formula provide a better refractive prediction compared with old formulas. Intraoperatively, the chopping technique is preferred to minimize pressure on weak zonules and reduce the incidence of posterior capsule rupture. Anterior capsular polishing is recommended to reduce the risk of postoperative capsular contraction syndrome (CCS). Postoperatively, complications such as refractive surprises, intraocular pressure spikes, and CCS remain higher in myopic eyes. Only 63\% of myopic patients with axial length more than 26 mm achieve a visual acuity at least 20/40 after cataract surgery, mainly because of coexisting ocular comorbidities. SUMMARY: There are multiple preoperative, intraoperative, and postoperative considerations when performing cataract surgery in myopic eyes. Further research is needed to optimize the refractive outcomes in these eyes and determine the best IOL formula. Surgeons should be adept and knowledgeable with different techniques to manage intraoperative complications.},
	keywords = {Cataract, Humans},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000914},
	author = {Elhusseiny, Abdelrahman M and Salim, Sarwat}
}
@article {1698291,
	title = {Ahmed and Baerveldt Glaucoma Drainage Devices in Childhood Glaucoma: A Meta-Analysis},
	journal = {J Glaucoma},
	volume = {32},
	number = {8},
	year = {2023},
	month = {2023 Aug 01},
	pages = {686-694},
	abstract = {PRCIS: The effectiveness of Ahmed glaucoma valve (AGV) and Baerveldt glaucoma implant (BGI) was comparable in the management of childhood glaucoma over the long term despite initial better success rate with BGI. There were higher tube block and retraction rates in the BGI group and higher tube exposure rates in the AGV group. PURPOSE: To evaluate the outcomes and safety of AGV and BGI in childhood glaucoma. MATERIALS AND METHODS: We performed a systematic literature review of publications from 1990 to 2022 in PubMed, EMBASE, ClinicalTrials.gov, Ovid MEDLINE, Cochrane CENTRAL, and google scholar for studies evaluating AGV and BGI in childhood glaucoma. Primary outcome measures were intraocular pressure (IOP) reduction and glaucoma medication reduction. The secondary outcome measures were the success rates and incidence of postoperative complications. We conducted a meta-analysis using a random effects model. RESULTS: Thirty-two studies met the inclusion criteria. A total of 1480 eyes were included. The mean IOP reduction was 15.08 mm Hg ( P \&lt; 0.00001) for AGV and 14.62 ( P \&lt; 0.00001) for the BGI group. The mean difference between pre and postoperative glaucoma medications was 1 ( P \&lt; 0.00001) fewer medications in the AGV group and 0.95 ( P \&lt; 0.0001) fewer medications in the BGI group. There was a lower success rate in the AGV versus BGI groups at 2 years [63\% vs 83\%, respectively ( P \&lt; 0.0001) and 3 years (43\% vs 79\%, respectively ( P \&lt; 0.0001)]; however, the success was higher for AGV at 5 years (63\% vs 56\% in the BGI group, P \&lt; 0.001). The incidence of postoperative complications was comparable in the AGV and BGI groups, with rates of 28\% and 27\%, respectively. CONCLUSIONS: The IOP and glaucoma medication reduction, success rates, and incidence of postoperative complications were comparable in Ahmed and Baerveldt groups. Most literature comes from retrospective low-quality studies on refractory childhood glaucoma. Further larger cohort studies are needed.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002235},
	author = {Elhusseiny, Abdelrahman M and Hassan, Amr K and Azhari, Jamal O and Elkheniny, Fatmah D and Chauhan, Muhammad Z and Chang, Ta C and VanderVeen, Deborah K and Oke, Isdin and Mansour, Munthir and Pakravan, Mohammad and Shaarawy, Tarek and Sallam, Ahmed B}
}
@article {1798311,
	title = {Comment on: Light as a drug: prospective randomized evaluation and comparison of the effect of decreased illumination on visual recovery following cataract surgery},
	journal = {J Cataract Refract Surg},
	volume = {50},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {314-315},
	keywords = {Cataract Extraction, Humans, Lighting, Prospective Studies, Randomized Controlled Trials as Topic},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000001401},
	author = {Elhusseiny, Abdelrahman M and Chuahan, Muhammad Z and Sallam, Ahmed B}
}
@article {753691,
	title = {CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 20-2016. A 50-Year-Old Man with Cloudy Vision, Hearing Loss, and Unsteadiness.},
	journal = {N Engl J Med},
	volume = {374},
	number = {26},
	year = {2016},
	month = {2016 Jun 30},
	pages = {2586-93},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc1600611},
	author = {Eliott, Dean and Papaliodis, George N and Durand, Marlene L and Turbett, Sarah E}
}
@article {935671,
	title = {SMOKING IS A RISK FACTOR FOR PROLIFERATIVE VITREORETINOPATHY AFTER TRAUMATIC RETINAL DETACHMENT},
	journal = {Retina},
	volume = {37},
	number = {7},
	year = {2017},
	month = {2017 Jul},
	pages = {1229-1235},
	abstract = {PURPOSE: To determine the incidence of retinal redetachment due to proliferative vitreoretinopathy after open-globe trauma in smokers and nonsmokers. METHODS: A total of 892 patients comprising 893 open-globe injuries, in whom 255 eyes were diagnosed with a retinal detachment, and 138 underwent surgical repair were analyzed in a retrospective case-control study. Time to redetachment was examined using the Kaplan-Meier method and analysis of risk factors was analyzed using Cox proportional hazards modeling. RESULTS: Within one year after retinal detachment surgery, 47\% (95\% CI, 39-56\%) of all 138 repaired retinas redetached because of proliferative vitreoretinopathy. Being a smoker was associated with a higher rate of detachment (adjusted hazard ratio 1.96, P = 0.01). As shown in previous studies, the presence of proliferative vitreoretinopathy at the time of surgery was also an independent risk factor for failure (adjusted hazard ratio 2.13, P = 0.005). Treatment with vitrectomy-buckle compared favorably to vitrectomy alone (adjusted hazard ratio 0.58, P = 0.04). Only 8\% of eyes that redetached achieved a best-corrected visual acuity of 20/200 or better, in comparison to 44\% of eyes that did not redetach (P \&lt; 0.001). CONCLUSION: Proliferative vitreoretinopathy is a common complication after the repair of retinal detachment associated with open-globe trauma, and being a smoker is a risk factor for redetachment. Further study is needed to understand the pathophysiologic mechanisms underlying this correlation.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001361},
	author = {Eliott, Dean and Stryjewski, Tomasz P and Andreoli, Michael T and Andreoli, Christopher M}
}
@article {1417557,
	title = {Bioactive lipids and pathological retinal angiogenesis},
	journal = {Br J Pharmacol},
	volume = {176},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {93-109},
	abstract = {Angiogenesis, disruption of the retinal barrier, leukocyte-adhesion and oedema are cardinal signs of proliferative retinopathies that are associated with vision loss. Therefore, identifying factors that regulate these vascular dysfunctions is critical to target pathological angiogenesis. Given the conflicting role of bioactive lipids reported in the current literature, the goal of this review is to provide the reader a clear road map of what has been accomplished so far in the field with specific focus on the role of polyunsaturated fatty acids (PUFAs)-derived metabolites in proliferative retinopathies. This necessarily entails a description of the different retina cells, blood retina barriers and the role of (PUFAs)-derived metabolites in diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration as the most common types of proliferative retinopathies.},
	issn = {1476-5381},
	doi = {10.1111/bph.14507},
	author = {Elmasry, Khaled and Ibrahim, Ahmed S and Abdulmoneim, Samer and Al-Shabrawey, Mohamed}
}
@article {1806551,
	title = {The Use of Ologen Implant in Childhood Glaucoma Surgeries: A Review},
	journal = {Curr Eye Res},
	year = {2024},
	month = {2024 Feb 12},
	pages = {1-7},
	abstract = {PURPOSE: This study assesses the effectiveness and safety of using Ologen implants (Aeon Astron Europe BV, Leiden, The Netherlands) as an adjunctive therapy in childhood glaucoma surgeries. METHODS: We systematically reviewed the existing literature across various electronic databases to examine the effectiveness and safety of Ologen implants in childhood glaucoma surgeries. RESULTS: Our analysis encompassed 14 studies on the use of Ologen implants in childhood glaucoma. Among these, seven were prospective, five were retrospective, and two did not specify their study design. Success rates varied depending on the type of surgery and the included childhood glaucoma subtype. The success rates for Ologen implants-augmented surgeries were as follows: 33.3-70\% for trabeculectomy, 50-81\% for combined trabeculotomy-trabeculectomy procedure, 33\%-87\% for glaucoma drainage device, and 60\% in deep sclerectomy. CONCLUSION: Ologen implant has a potential role in mitigating postoperative fibrosis and enhancing success rates in various childhood glaucoma surgeries. However, the existing literature is limited. Future comparative prospective studies with larger cohorts are needed.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2024.2312944},
	author = {Elwehidy, Ahmed S and Toma, Joseph and Abd Elfattah, Dina and Elhusseiny, Abdelrahman M}
}
@article {314131,
	title = {Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival.},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {252},
	number = {11},
	year = {2014},
	month = {2014 Nov},
	pages = {1755-62},
	abstract = {PURPOSE: To investigate the effect of VEGF-C and VEGF-D blockade via soluble VEGFR-3 (sVEGFR-3) on T cell allosensitization, corneal neovascularization, and transplant survival. METHODS: Corneal intrastromal suture placement and allogeneic transplantation were performed on BALB/c mice to evaluate the effect of sVEGFR-3 on corneal neovascularization. Soluble VEGFR-3 trap was injected intraperitoneally to block VEGF-C/D (every other day starting the day of surgery). Immunohistochemical staining of corneal whole mounts was performed using anti-CD31 (PECAM-1) and anti-LYVE-1 antibodies to quantify the levels of hem- and lymphangiogenesis, respectively. Mixed lymphocyte reaction (MLR) was performed to assess indirect and direct host T cell allosensitization and the frequencies of IFN-γ-producing T cells in the draining lymph nodes were assessed using flow cytometry. Graft opacity and survival was evaluated by slit-lamp biomicroscopy. RESULTS: Treatment with sVEGFR-3 resulted in a significant blockade of lymphangiogenesis 2 weeks post-transplantation and significantly prolonged corneal allograft survival compared to the control group at 8 weeks post-transplantation (87.5 \% vs. 50 \%), and this was associated with significant reduction in the frequencies of allosensitized T cells and decreased frequencies of IFN-γ-producing CD4 T cells. CONCLUSIONS: Soluble VEGFR-3 suppresses corneal lymphangiogenesis and allograft rejection and may offer a viable therapeutic modality for corneal neovascularization and corneal transplantation.},
	issn = {1435-702X},
	doi = {10.1007/s00417-014-2749-5},
	author = {Emami-Naeini, Parisa and Dohlman, Thomas H and Omoto, Masahiro and Hattori, Takaaki and Chen, Yihe and Lee, Hyun Soo and Chauhan, Sunil K and Dana, Reza}
}
@article {1363274,
	title = {Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors},
	journal = {Dev Cell},
	volume = {26},
	number = {1},
	year = {2013},
	month = {2013 Jul 15},
	pages = {59-72},
	abstract = {Cone photoreceptors carry out phototransduction in daylight conditions and provide the critical first step in color vision. Despite their importance, little is known about the developmental mechanisms involved in their generation, particularly how they are determined relative to rod photoreceptors, the cells that initiate vision in dim light. Here, we report the identification of a cis-regulatory module (CRM) for the thyroid hormone receptor beta (Thrb) gene, an early cone marker. We found that ThrbCRM1 is active in progenitor cells biased to the production of cones and an interneuronal cell type, the horizontal cell (HC). Molecular analysis of ThrbCRM1 revealed that it is combinatorially regulated by the Otx2 and Onecut1 transcription factors. Onecut1 is sufficient to induce cells with the earliest markers of cones and HCs. Conversely, interference with Onecut1 transcriptional activity leads to precocious rod development, suggesting that Onecut1 is critically important in defining cone versus rod fates.},
	keywords = {Animals, Cell Lineage, Chick Embryo, Chickens, Electroporation, Gene Expression Regulation, Developmental, Hepatocyte Nuclear Factor 6, Mice, Mice, Knockout, Otx Transcription Factors, Regulatory Elements, Transcriptional, Retina, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, RNA, Messenger, Stem Cells, Thyroid Hormone Receptors beta, Transcription, Genetic},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2013.06.005},
	author = {Emerson, Mark M and Surzenko, Natalia and Goetz, Jillian J and Trimarchi, Jeffrey and Cepko, Constance L}
}
@article {1498240,
	title = {Electrical Stimulation Induces Retinal M{\"u}ller Cell Proliferation and Their Progenitor Cell Potential},
	journal = {Cells},
	volume = {9},
	number = {3},
	year = {2020},
	month = {2020 Mar 23},
	abstract = {Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our previous study suggested that ES promoted retinal function and the proliferation of progenitor-like glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism remains obscure. M{\"u}ller cells (MCs) are thought to be dormant residential progenitor cells that possess a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a ramp waveform of 20 Hz and 300 {\textmu}A of current was effective at inducing mouse MC proliferation and enhancing their expression of progenitor cell markers, such as (cone-rod homeobox) and , as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing revealed that calcium signaling pathway activation was a key event, with a false discovery rate of 5.33 {\texttimes} 10 ( = 1.78 {\texttimes} 10) in ES-mediated gene profiling changes. Moreover, the calcium channel blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene induction, supporting a central role of ES-induced Ca signaling in the MC changes. Our results suggest that low-current ES may present a convenient tool for manipulating MC behavior toward neuroregeneration and repair.},
	issn = {2073-4409},
	doi = {10.3390/cells9030781},
	author = {Enayati, Sam and Chang, Karen and Achour, Hamida and Cho, Kin-Sang and Xu, Fuyi and Guo, Shuai and Z Enayati, Katarina and Xie, Jia and Zhao, Eric and Turunen, Tytteli and Sehic, Amer and Lu, Lu and Utheim, Tor Paaske and Chen, Dong Feng}
}
@article {1354333,
	title = {Adjustable sutures in children},
	journal = {J AAPOS},
	volume = {18},
	number = {3},
	year = {2014},
	month = {2014 Jun},
	pages = {278-84},
	abstract = {Although adjustable sutures are considered a standard technique in adult strabismus surgery, most surgeons are hesitant to attempt the technique in children, who are believed to be unlikely to cooperate for postoperative assessment and adjustment. Interest in using adjustable sutures in pediatric patients has increased with the development of surgical techniques specific to infants and children. This workshop briefly reviews the literature supporting the use of adjustable sutures in children and presents the approaches currently used by three experienced strabismus surgeons.},
	keywords = {Child, Child, Preschool, Humans, Infant, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Retrospective Studies, Strabismus, Suture Techniques},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2013.12.015},
	author = {Engel, J Mark and Guyton, David L and Hunter, David G}
}
@article {1586191,
	title = {Why They Took the Oath: A Spotlight on Resident Sacrifice During the Pandemic},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {1},
	year = {2021},
	month = {2021 Mar 01},
	pages = {1-5},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001202},
	author = {Engelhard, Stephanie B and Bruce, Samuel S and Chwalisz, Bart K and Dinkin, Marc J}
}
@article {1593865,
	title = {Dropped Nucleus during Cataract Surgery in South India: Incidence, Risk Factors, and Outcomes},
	journal = {Ophthalmic Epidemiol},
	volume = {29},
	number = {3},
	year = {2022},
	month = {2022 Jun},
	pages = {271-278},
	abstract = {PURPOSE: To determine incidence, risk factors for, and outcomes of dropped nucleus (DN) during cataract surgery. METHODS: This is a matched case-control study at the Aravind Eye Hospital in Madurai, India. Out of 184 consecutive DN cases, 171 were included. The case immediately preceding the DN case by the same surgeon served as matched concurrent control. The proportion of cataract surgeries with DN was calculated with a 95\% confidence interval (CI). Conditional logistic regression was used to generate odds ratios for potential risk factors. RESULTS: Among 415,487 consecutive cataract surgeries, incidence risk of DN was 0.044\% [95\% CI 0.038\%, 0.051\%], or 0.44 per 1,000 surgeries in 52\&nbsp;months. Significant preoperative risk factors were posterior polar cataract (adjusted odds ratio [aOR] 21.73, p =\&nbsp;.003); suspected loose zonules (aOR 8.85, p \&lt;\&nbsp;.001); older age (aOR 1.57, p =\&nbsp;.001); and presence of diabetes mellitus (aOR 1.79, p =\&nbsp;.03). Associated intraoperative complications included zonular dialysis (OR 34.49, p \&lt;\&nbsp;.001), vitreous disturbance (OR 193.36, p \&lt;\&nbsp;.001), and posterior capsule rent (OR 384.39, p \&lt;\&nbsp;.001). Phacoemulsification and manual small incision cataract surgery did not significantly differ in DN incidence. DN most commonly occurred during nucleus removal (35.1\%) or during/immediately following hydrodissection (24.0\%). Visual outcomes of DN were worse than controls on average, but 51.9\% achieved visual acuity 20/40 or better at 1 month. CONCLUSIONS: DN occurred rarely, with low absolute risk even when a strong risk factor was present. Nearly all cases followed posterior capsular rent or zonular dialysis, usually with observed vitreous loss. In spite of increased risk of postoperative complications in the DN group, the majority achieved favorable results.},
	keywords = {Case-Control Studies, Cataract, Cataract Extraction, Humans, Incidence, India, Intraoperative Complications, Postoperative Complications, Retrospective Studies, Risk Factors},
	issn = {1744-5086},
	doi = {10.1080/09286586.2021.1923756},
	author = {Engelhard, Stephanie B and Haripriya, Aravind and Namburar, Sathvik and Pistilli, Maxwell and Daniel, Ebenezer and Kempen, John H}
}
@article {1363275,
	title = {Intravitreal injections at the Massachusetts Eye and Ear Infirmary: analysis of treatment indications and postinjection endophthalmitis rates},
	journal = {Br J Ophthalmol},
	volume = {97},
	number = {4},
	year = {2013},
	month = {2013 Apr},
	pages = {460-5},
	abstract = {AIM: To report the incidence rate of acute postoperative endophthalmitis secondary to therapeutic intravitreal injections. METHODS: A retrospective review of all consecutive eyes after intravitreal injections was performed at the Massachusetts Eye and Ear Infirmary, Boston, from 1 January 2007 to 31 December 2011. RESULTS: During the 5-year study interval, 10 208 intravitreal injections were performed. The overall incidence rate of endophthalmitis was 0.029\% per injection (3 of 10 208 injections). In the three cases, in our series, the endophthalmitis occurred at an average of seven injections, which lies within the SD of the mean number of injections received by each eye in this study, suggesting approximately equal probability of infection for each eye after receiving multiple, sequential injections. Bacterial cultures and Gram stain revealed coagulase-negative Staphylococcus species (n=1), moderate bacteria with negative culture (n=1) and moderate Staphylococcus epidermidis (n=1). All cases were successfully treated using either intravitreal antibiotics and steroids or pars plana vitrectomy. Best-corrected visual acuity reduction was not clinically significant at the last visit (\&gt;7 months for all cases). CONCLUSIONS: Acute endophthalmitis is a rare potential complication after intravitreal injection. Further studies are required to elucidate the best prophylactic and aseptic techniques to prevent this rare complication.},
	keywords = {Academic Medical Centers, Acute Disease, Aged, Angiogenesis Inhibitors, Anti-Bacterial Agents, Antibodies, Monoclonal, Humanized, Aptamers, Nucleotide, Bevacizumab, Endophthalmitis, Eye Infections, Bacterial, Female, Humans, Incidence, Intravitreal Injections, Male, Massachusetts, Postoperative Complications, Ranibizumab, Retinal Diseases, Retrospective Studies, Triamcinolone Acetonide, Vascular Endothelial Growth Factor A, Visual Acuity},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2012-302435},
	author = {Englander, Miriam and Chen, Teresa C and Paschalis, Eleftherios I and Miller, Joan W and Kim, Ivana K}
}
@article {1016031,
	title = {Identification and Profiling of Specialized Pro-Resolving Mediators in Human Tears by Lipid Mediator Metabolomics},
	journal = {Prostaglandins Leukot Essent Fatty Acids},
	volume = {117},
	year = {2017},
	month = {2017 Feb},
	pages = {17-27},
	abstract = {Specialized pro-resolving mediators (SPM), e.g. Resolvin D1, Protectin D1, Lipoxin A$_{4}$, and Resolvin E1 have each shown to be active in ocular models reducing inflammation. In general, SPMs have specific agonist functions that stimulate resolution of infection and inflammation in animal disease models. The presence and quantity of SPM in human emotional tears is of interest. Here, utilizing a targeted LC-MS-MS metabololipidomics based approach we document the identification of pro-inflammatory (Prostaglandins and Leukotriene B$_{4}$) and pro-resolving lipid mediators (D-series Resolvins, Protectin D1, and Lipoxin A$_{4}$) in human emotional tears from 12 healthy individuals. SPMs from the Maresin family (Maresin 1 and Maresin 2) were not present in these samples. Principal Component Analysis (PCA) revealed gender differences in the production of specific mediators within these tear samples as the SPMs were essentially absent in these female donors. These results indicate that specific SPM signatures are present in human emotional tears at concentrations known to be bioactive. Moreover, they will help to further appreciate the mechanisms of production and action of SPMs in the eye, as well as their physiologic roles in human ocular disease resolution.},
	issn = {1532-2823},
	doi = {10.1016/j.plefa.2017.01.004},
	author = {English, Justin T and Norris, Paul C and Hodges, Robin R and Dartt, Darlene A. and Serhan, Charles N}
}
@article {280816,
	title = {Modelling of human uveal melanoma in Zebrafish xenograft embryos.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2014},
	month = {2014 Sep 23},
	abstract = {PURPOSE. Uveal melanoma (UM) is fatal in up to 50\% of patients because of liver metastases, that are refractory to therapies currently available. While murine xenograft models for human uveal melanoma are available, they have limited utility for screening large compound libraries in drug discovery studies. Therefore, new robust preclinical models are needed that can efficiently evaluate drug efficacy for treatment of this malignancy. METHODS. UM cell lines generated from primary tumors (92.1, Mel270) and metastases (OMM2.3, OMM2.5, OMM1) were injected into the yolk of two-day-old zebrafish embryos. After six days, proliferation and active migration was quantified via automated confocal image analysis. To determine the suitability of this xenotransplantation model for drug testing, drugs with three different activities (Dasatinib, Quisinostat and MLN-4924) were added to the water of uveal melanoma-engrafted embryos. RESULTS. All tested UM cell lines proliferated and migrated in the embryos; significant differences could be discerned between cell lines: cells derived from metastases showed more migration and proliferation than cells derived from the primary tumors, and provided preclinical models for drug testing. Addition of the Src-inhibitor Dasatinib in the water of engrafted embryos reduced proliferation and migration of high Src-expressing 92.1 cells, but did not affect low Src-expressing metastatic OMM2.3 cells. Two experimental anticancer drugs, Quisinostat (a histone deacetylase inhibitor) and MLN-4924 (neddylation pathway inhibitor), blocked migration and proliferation of 92.1 and OMM2.3. CONCLUSIONS. We established a zebrafish xenograft model of human uveal melanoma with demonstrated applicability for screening large libraries of compounds in drug discovery studies.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15202},
	author = {van der Ent, Wietske and Burrello, Claudia and Teunisse, Amina F A S and Ksander, Bruce R and Van der Velden, Pieter A and Jager, Martine J and Jochemsen, A G and Snaar-Jagalska, B Ewa}
}
@article {1532365,
	title = {Antimicrobial Photodynamic Therapy as a Potential Treatment Against COVID-19: A Case for Blue Light},
	journal = {Photobiomodul Photomed Laser Surg},
	volume = {38},
	number = {10},
	year = {2020},
	month = {2020 10},
	pages = {577-578},
	keywords = {Betacoronavirus, Coronavirus Infections, Humans, Pandemics, Phototherapy, Pneumonia, Viral},
	issn = {2578-5478},
	doi = {10.1089/photob.2020.4901},
	author = {Enwemeka, Chukuka S and Baker, Terrance L and Greiner, Jack V and Bumah, Violet V and Masson-Meyers, Daniela S and Castel, John Chris and Vesonder, Modesta}
}
@article {1642010,
	title = {Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function},
	journal = {Science},
	volume = {376},
	number = {6594},
	year = {2022},
	month = {2022 05 13},
	pages = {eabl4290},
	abstract = {Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.},
	keywords = {Biomarkers, Cell Nucleus, Disease, Genome-Wide Association Study, Humans, Organ Specificity, Phenotype, RNA-Seq},
	issn = {1095-9203},
	doi = {10.1126/science.abl4290},
	author = {Eraslan, G{\"o}kcen and Drokhlyansky, Eugene and Anand, Shankara and Fiskin, Evgenij and Subramanian, Ayshwarya and Slyper, Michal and Wang, Jiali and Van Wittenberghe, Nicholas and Rouhana, John M and Waldman, Julia and Ashenberg, Orr and Lek, Monkol and Dionne, Danielle and Win, Thet Su and Cuoco, Michael S and Kuksenko, Olena and Tsankov, Alexander M and Branton, Philip A and Marshall, Jamie L and Greka, Anna and Getz, Gad and Segr{\`e}, Ayellet V and Aguet, Fran{\c c}ois and Rozenblatt-Rosen, Orit and Ardlie, Kristin G and Regev, Aviv}
}
@article {1798541,
	title = {Unusual Pediatric Red Eye},
	journal = {J Pediatr},
	volume = {267},
	year = {2024},
	month = {2024 Apr},
	pages = {113924},
	keywords = {Child, Diagnosis, Differential, Eye, Humans, Vision Disorders},
	issn = {1097-6833},
	doi = {10.1016/j.jpeds.2024.113924},
	author = {Ercanbrack, Carson W and Azhari, Jamal O and Warner, David B and Abulfaraj, Maher and Elhusseiny, Abdelrahman M}
}
@article {1517171,
	title = {TFOS European ambassador meeting: Unmet needs and future scientific and clinical solutions for ocular surface diseases},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 Jun 03},
	abstract = {The mission of the Tear Film \&amp; Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II{\texttrademark}, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.05.006},
	author = {Erickson, Susan and Sullivan, Amy Gallant and Barabino, Stefano and Begovic, Enesa and Benitez-Del-Castillo, Jose M and Bonini, Stefano and Borges, Jos{\'e} Salgado and Brzheskiy, Vladimir and Bulat, Nina and Cerim, Alma and Craig, P and Cusnir, Valeriu and Cusnir, Valeriu and Cusnir, Vitalie and Doan, Serge and D{\"u}lger, Erol and Farrant, Sarah and Geerling, Gerd and Goldblum, David and Golubev, Sergey and Gomes, Jos{\'e} A P and Gonz{\'a}lez-M{\'e}ijome, Jos{\'e} Manuel and Grupcheva, Christina N and G{\"u}nd{\"u}z, {\"O}m{\"u}r U{\c c}akhan and Horwath-Winter, Jutta and K{\"a}llmark, Fredrik and Karanadze, Nino and Karcic, Huda Hajjir and Karcic, Suvad and Kontadakis, Georgios and Messmer, Elisabeth M and Mrugacz, Malgorzata and Murphy, Conor and O{\textquoteright}Leary, Olivia E and Procopciuc, Vitalie and Pult, Heiko and Raus, Peter and {\c S}ahin, Afsun and Set{\"a}l{\"a}, Niko and Stanila, Adriana and Stanila, Dan Mircea and Utheim, Tor Paaske and Vehof, Jelle and Versura, Piera and Villani, Edoardo and Willcox, Mark D P and Wolffsohn, James S and Zag{\'o}rski, Zbigniew and Zoega, Gunnar M{\'a}r and Sullivan, David A and Moderators and Gomes, Jos{\'e} A P and Versura, Piera and Willcox, Mark D P}
}
@article {1445339,
	title = {The Role of Botulinum Toxin in the Treatment of Strabismus},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 08},
	pages = {1-7},
	abstract = {: To perform a systematic review of the application of botulinum toxin A (BTA) in the management of strabismus in the adult and pediatric populations. : A systematic literature search was performed using the Medline database. : In 1989, with the FDA approval of botulinum toxin (onabotulinum toxin A, or BTA) for the treatment of strabismus, patients were provided with an alternative to surgical recession. In this review, we discuss the uses of BTA in the treatment of acute onset comitant esotropia or smaller angle esotropia and as an adjunct to surgery for larger angle esotropia or sixth nerve palsy. Its uses are also explored in intermittent exotropia and vertical strabismus, including thyroid-associated orbitopathy, fourth nerve palsies, and other orbital pathology. : Despite its transient kinetics, BTA can have permanent effects on ocular alignment, promoting binocularity and reduction of diplopia, and can serve as a primary treatment or a muscle sparing option in patients at risk of anterior segment ischemia or need for future surgeries.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620795},
	author = {Escuder, Anna G and Hunter, David G}
}
@article {1538329,
	title = {Incidence of symptomatic vertical and torsional diplopia after superior rectus transposition for esotropic Duane syndrome and abducens nerve palsy},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Oct 09},
	abstract = {PURPOSE: To report the incidence of symptomatic vertical and torsional diplopia after superior rectus transposition (SRT) for esotropic Duane syndrome and abducens nerve palsy. METHODS: The medical records of patients with esotropic Duane syndrome or abducens nerve palsy seen at Boston Children{\textquoteright}s Hospital (2006-2018) and treated with unilateral SRT with or without augmentation was performed. The primary outcome was incidence of postoperative vertical or torsional diplopia in primary position. The secondary outcome was induced vertical deviation in affected side gaze. RESULTS: A total of 69 patients met inclusion criteria: 32 with abducens nerve palsy and 37 with esotropic Duane syndrome. Vertical alignment changed in both hyper- and hypotropic directions. Median pre- and postoperative vertical deviation in primary gaze was 1.1 (10th-90th percentile, 0-6 hypertropia) and 0.4 (10th-90th percentile, 6 hypotropia to 8 hypertropia), respectively. Postoperative vertical diplopia occurred in 7\%, including 4 of 49 treated with loop myopexy (8\%), 1 of 13 without augmentation (8\%), and 0 of 7 treated with sclera-fixated augmentation. All but one was successfully treated with prism or secondary surgery. Intorsional change predominated, but no patient had torsional diplopia post adjustment. Vertical misalignment in affected side gaze increased from 19\% to 45\% after SRT (P = 0.01). CONCLUSIONS: In this largest-to-date review of patients treated with SRT, with or without MR recession, no patient developed persistent torsional diplopia, while 7\% developed symptomatic vertical diplopia in primary position, similar to the reported incidence after balanced vertical rectus transposition. Vertical misalignment in affected side gaze increased, however fusion is already limited by unresolved esotropia in this field.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.05.014},
	author = {Escuder, Anna G and Kazlas, Melanie A and Heidary, Gena and Hunter, David G and Zurakowski, David and Dagi, Linda R}
}
@article {1667698,
	title = {PyVisualFields: A Python Package for Visual Field Analysis},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {6},
	abstract = {PURPOSE: Artificial intelligence (AI) methods are changing all areas of research and have a variety of capabilities of analysis in ophthalmology, specifically in visual fields (VFs) to detect or predict vision loss progression. Whereas most of the AI algorithms are implemented in Python language, which offers numerous open-source functions and algorithms, the majority of algorithms in VF analysis are offered in the R language. This paper introduces PyVisualFields, a developed package to address this gap and make available VF analysis in the Python language. METHODS: For the first version, the R libraries for VF analysis provided by vfprogression and visualFields packages are analyzed to define the overlaps and distinct functions. Then, we defined and translated this functionality into Python with the help of the wrapper library rpy2. Besides maintaining, the subsequent versions{\textquoteright} milestones are established, and the third version will be R-independent. RESULTS: The developed Python package is available as open-source software via the GitHub repository and is ready to be installed from PyPI. Several Jupyter notebooks are prepared to demonstrate and describe the capabilities of the PyVisualFields package in the categories of data presentation, normalization and deviation analysis, plotting, scoring, and progression analysis. CONCLUSIONS: We developed a Python package and demonstrated its functionality for VF analysis and facilitating ophthalmic research in VF statistical analysis, illustration, and progression prediction. TRANSLATIONAL RELEVANCE: Using this software package, researchers working on VF analysis can more quickly create algorithms for clinical applications using cutting-edge AI techniques.},
	keywords = {Algorithms, Artificial Intelligence, Proteomics, Software, Visual Fields},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.2.6},
	author = {Eslami, Mohammad and Kazeminasab, Saber and Sharma, Vishal and Li, Yangjiani and Fazli, Mojtaba and Wang, Mengyu and Zebardast, Nazlee and Tobias Elze}
}
@article {1709656,
	title = {A unique color-coded visualization system with multimodal information fusion and deep learning in a longitudinal study of Alzheimer{\textquoteright}s disease},
	journal = {Artif Intell Med},
	volume = {140},
	year = {2023},
	month = {2023 Jun},
	pages = {102543},
	abstract = {PURPOSE: Automated diagnosis and prognosis of Alzheimer{\textquoteright}s Disease remain a challenging problem that machine learning (ML) techniques have attempted to resolve in the last decade. This study introduces a first-of-its-kind color-coded visualization mechanism driven by an integrated ML model to predict disease trajectory in a 2-year longitudinal study. The main aim of this study is to help capture visually in 2D and 3D renderings the diagnosis and prognosis of AD, therefore augmenting our understanding of the processes of multiclass classification and regression analysis. METHOD: The proposed method, Machine Learning for Visualizing AD (ML4VisAD), is designed to predict disease progression through a visual output. This newly developed model takes baseline measurements as input to generate a color-coded visual image that reflects disease progression at different time points. The architecture of the network relies on convolutional neural networks. With 1123 subjects selected from the ADNI QT-PAD dataset, we use a 10-fold cross-validation process to evaluate the method. Multimodal inputs* include neuroimaging data (MRI, PET), neuropsychological test scores (excluding MMSE, CDR-SB, and ADAS to avoid bias), cerebrospinal fluid (CSF) biomarkers with measures of amyloid beta (ABETA), phosphorylated tau protein (PTAU), total tau protein (TAU), and risk factors that include age, gender, years of education, and ApoE4 gene. FINDINGS/RESULTS: Based on subjective scores reached by three raters, the results showed an accuracy of 0.82\&nbsp;{\textpm}\&nbsp;0.03 for a 3-way classification and 0.68\&nbsp;{\textpm}\&nbsp;0.05 for a 5-way classification. The visual renderings were generated in 0.08\&nbsp;msec for a 23\&nbsp;{\texttimes}\&nbsp;23 output image and in 0.17\&nbsp;ms for a 45\&nbsp;{\texttimes}\&nbsp;45 output image. Through visualization, this study (1) demonstrates that the ML visual output augments the prospects for a more accurate diagnosis and (2) highlights why multiclass classification and regression analysis are incredibly challenging. An online survey was conducted to gauge this visualization platform{\textquoteright}s merits and obtain valuable feedback from users. All implementation codes are shared online on GitHub. CONCLUSION: This approach makes it possible to visualize the many nuances that lead to a specific classification or prediction in the disease trajectory, all in context to multimodal measurements taken at baseline. This ML model can serve as a multiclass classification and prediction model while reinforcing the diagnosis and prognosis capabilities by including a visualization platform.},
	keywords = {Alzheimer Disease, Amyloid beta-Peptides, Cognitive Dysfunction, Deep Learning, Disease Progression, Humans, Longitudinal Studies, Magnetic Resonance Imaging, tau Proteins},
	issn = {1873-2860},
	doi = {10.1016/j.artmed.2023.102543},
	author = {Eslami, Mohammad and Tabarestani, Solale and Adjouadi, Malek}
}
@article {1295862,
	title = {Cornea-Derived Mesenchymal Stromal Cells Therapeutically Modulate Macrophage Immunophenotype and Angiogenic Function},
	journal = {Stem Cells},
	volume = {36},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {775-784},
	abstract = {Macrophages are crucial drivers of inflammatory corneal neovascularization and thus are potential targets for immunomodulatory therapies. We hypothesized that therapeutic use of cornea-derived mesenchymal stromal cells (cMSCs) may alter the function of macrophages. We found that cMSCs can modulate the phenotype and angiogenic function of macrophages. In vitro, cMSCs induce apoptosis of macrophages while preferentially promoting a distinct CD14 CD16 CD163 CD206 immunophenotype that has significantly reduced angiogenic effects based on in vitro angiogenesis assays. In vivo, application of cMSCs to murine corneas after injury leads to reduced macrophage infiltration and higher expression of CD206 in macrophages. Macrophages cocultured ("educated") by cMSCs express significantly higher levels of anti-angiogenic and anti-inflammatory factors compared with control macrophages. In vivo, injured corneas treated with cMSC-educated macrophages demonstrate significantly less neovascularization compared with corneas treated with control macrophages. Knocking down the expression of pigment epithelial derived factor (PEDF) in cMSCs significantly abrogates its modulating effects on macrophages, as shown by the reduced rate of apoptosis, decreased expression of sFLT-1/PEDF, and increased expression of vascular endothelial growth factor-A in the cocultured macrophages. Similarly, cMSCs isolated from PEDF knockout mice are less effective compared with wild-type cMSCs at inhibiting macrophage infiltration when applied to wild-type corneas after injury. Overall, these results demonstrate that cMSCs therapeutically suppress the angiogenic capacity of macrophages and highlight the role of cMSC secreted PEDF in the modulation of macrophage phenotype and function. Stem Cells 2018;36:775-784.},
	issn = {1549-4918},
	doi = {10.1002/stem.2781},
	author = {Eslani, Medi and Putra, Ilham and Shen, Xiang and Hamouie, Judy and Tadepalli, Asha and Anwar, Khandaker N and Kink, John A and Ghassemi, Samaneh and Agnihotri, Gaurav and Reshetylo, Sofiya and Mashaghi, Alireza and Dana, Reza and Hematti, Peiman and Djalilian, Ali R}
}
@article {1478336,
	title = {High-throughput dense reconstruction of cell lineages},
	journal = {Open Biol},
	volume = {9},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {190229},
	abstract = {The first meeting exclusively dedicated to the {\textquoteright}High-throughput dense reconstruction of cell lineages{\textquoteright} took place at Janelia Research Campus (Howard Hughes Medical Institute) from 14 to 18 April 2019. Organized by Tzumin Lee, Connie Cepko, Jorge Garcia-Marques and Isabel Espinosa-Medina, this meeting echoed the recent eruption of new tools that allow the reconstruction of lineages based on the phylogenetic analysis of DNA mutations induced during development. Combined with single-cell RNA sequencing, these tools promise to solve the lineage of complex model organisms at single-cell resolution. Here, we compile the conference consensus on the technological and computational challenges emerging from the use of the new strategies, as well as potential solutions.},
	issn = {2046-2441},
	doi = {10.1098/rsob.190229},
	author = {Espinosa-Medina, Isabel and Garcia-Marques, Jorge and Cepko, Connie and Lee, Tzumin}
}
@article {369061,
	title = {Matching for Human Leukocyte Antigens (HLA) in corneal transplantation - To do or not to do.},
	journal = {Prog Retin Eye Res},
	volume = {46},
	year = {2015},
	month = {2015 May},
	pages = {84-110},
	abstract = {As many patients with severe corneal disease are not even considered as candidates for a human graft due to their high risk of rejection, it is essential to find ways to reduce the chance of rejection. One of the options is proper matching of the cornea donor and recipient for the Human Leukocyte Antigens (HLA), a subject of much debate. Currently, patients receiving their first corneal allograft are hardly ever matched for HLA and even patients undergoing a regraft usually do not receive an HLA-matched graft. While anterior and posterior lamellar grafts are not immune to rejection, they are usually performed in low risk, non-vascularized cases. These are the cases in which the immune privilege due to the avascular status and active immune inhibition is still intact. Once broken due to infection, sensitization or trauma, rejection will occur. There is enough data to show that when proper DNA-based typing techniques are being used, even low risk perforating corneal transplantations benefit from matching for HLA Class I, and high risk cases from HLA Class I and probably Class II matching. Combining HLA class I and class II matching, or using the HLAMatchmaker could further improve the effect of HLA matching. However, new techniques could be applied to reduce the chance of rejection. Options are the local or systemic use of biologics, or gene therapy, aiming at preventing or suppressing immune responses. The goal of all these approaches should be to prevent a first rejection, as secondary grafts are usually at higher risk of complications including rejections than first grafts.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2015.01.001},
	author = {van Essen, T H and Roelen, D L and Williams, K A and Jager, M J}
}
@article {1798511,
	title = {The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas},
	journal = {J Neuroophthalmol},
	volume = {44},
	number = {1},
	year = {2024},
	month = {2024 Mar 01},
	pages = {5-9},
	abstract = {BACKGROUND: Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs).

METHODS: Patients (\&lt;18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with >=1 year of follow-up. The central 30{\textdegree} NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations.

RESULTS: Eighty-two eyes of 41 children (56\% female) were included. The mean {\textpm} SD age at the first OCT was 10.1 {\textpm} 3.3 years, with a mean follow-up of 20.4 {\textpm} 7.2 months. At study entry, CAs were present in 46\% of eyes with a mean number of 2.1 {\textpm} 1.7 and a mean total area of 2.0 {\textpm} 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48\% of eyes with a mean number of 2.2 {\textpm} 1.8 lesions and a mean total area of 2.3 {\textpm} 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P \&gt; 0.05).

CONCLUSIONS: CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.},
	keywords = {Adolescent, Child, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Nerve Fibers, Neurofibromatosis 1, Optic Nerve Glioma, Prospective Studies, Retinal Ganglion Cells, Tomography, Optical Coherence},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000002075},
	author = {Estrela, Tais and Truong, Saprina and Garcia, Arielle and He, Jocelyn and Ying, Gui-Shuang and Devakandan, Keshini and Reginald, Y Arun and Fisher, Michael J and Liu, Grant T and Ullrich, Nicole J and Avery, Robert A and Heidary, Gena}
}
@article {1179161,
	title = {Corneal Collagen Cross-Linking Complications},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Sep 06},
	pages = {1-7},
	abstract = {Corneal cross-linking was approved by United States Food and Drug Administration for the treatment of progressive keratoconus in April 2016. As this approach becomes more widely used for the treatment of keratoconus and post-laser in situ keratomileusis (LASIK) ectasia, the medical community is becoming more familiar with potential complications associated with this procedure. This article aims to review the reported complications of collagen cross-linking for the treatment of keratoconus and post-LASIK ectasia.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353809},
	author = {Evangelista, Charisma B and Hatch, Kathryn M}
}
@article {882916,
	title = {A half-second glimpse often lets radiologists identify breast cancer cases even when viewing the mammogram of the opposite breast.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {113},
	number = {37},
	year = {2016},
	month = {2016 Sep 13},
	pages = {10292-7},
	abstract = {Humans are very adept at extracting the "gist" of a scene in a fraction of a second. We have found that radiologists can discriminate normal from abnormal mammograms at above-chance levels after a half-second viewing (d{\textquoteright} \~{} 1) but are at chance in localizing the abnormality. This pattern of results suggests that they are detecting a global signal of abnormality. What are the stimulus properties that might support this ability? We investigated the nature of the gist signal in four experiments by asking radiologists to make detection and localization responses about briefly presented mammograms in which the spatial frequency, symmetry, and/or size of the images was manipulated. We show that the signal is stronger in the higher spatial frequencies. Performance does not depend on detection of breaks in the normal symmetry of left and right breasts. Moreover, above-chance classification is possible using images from the normal breast of a patient with overt signs of cancer only in the other breast. Some signal is present in the portions of the parenchyma (breast tissue) that do not contain a lesion or that are in the contralateral breast. This signal does not appear to be a simple assessment of breast density but rather the detection of the abnormal gist may be based on a widely distributed image statistic, learned by experts. The finding that a global signal, related to disease, can be detected in parenchyma that does not contain a lesion has implications for improving breast cancer detection.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1606187113},
	author = {Evans, Karla K and Haygood, Tamara Miner and Cooper, Julie and Culpan, Anne-Marie and Wolfe, Jeremy M}
}
@article {416981,
	title = {Bell{\textquoteright}s palsy: aetiology, clinical features and multidisciplinary care.},
	journal = {J Neurol Neurosurg Psychiatry},
	year = {2015},
	month = {2015 Apr 9},
	abstract = {Bell{\textquoteright}s palsy is a common cranial neuropathy causing acute unilateral lower motor neuron facial paralysis. Immune, infective and ischaemic mechanisms are all potential contributors to the development of Bell{\textquoteright}s palsy, but the precise cause remains unclear. Advancements in the understanding of intra-axonal signal molecules and the molecular mechanisms underpinning Wallerian degeneration may further delineate its pathogenesis along with in vitro studies of virus-axon interactions. Recently published guidelines for the acute treatment of Bell{\textquoteright}s palsy advocate for steroid monotherapy, although controversy exists over whether combined corticosteroids and antivirals may possibly have a beneficial role in select cases of severe Bell{\textquoteright}s palsy. For those with longstanding sequaelae from incomplete recovery, aesthetic, functional (nasal patency, eye closure, speech and swallowing) and psychological considerations need to be addressed by the treating team. Increasingly, multidisciplinary collaboration between interested clinicians from a wide variety of subspecialties has proven effective. A patient centred approach utilising physiotherapy, targeted botulinum toxin injection and selective surgical intervention has reduced the burden of long-term disability in facial palsy.},
	issn = {1468-330X},
	doi = {10.1136/jnnp-2014-309563},
	author = {Eviston, Timothy J and Croxson, Glen R and Kennedy, Peter G E and Hadlock, Tessa and Krishnan, Arun V}
}
@inbook {1367076,
	title = {Enterococcus Diversity, Origins in Nature, and Gut Colonization},
	booktitle = {Enterococci: From Commensals to Leading Causes of Drug Resistant Infection [Internet]. Boston: Massachusetts Eye and Ear Infirmary; 2014-. },
	year = {2014},
	abstract = {Available from http://www.ncbi.nlm.nih.gov/books/NBK190427/},
	author = {Lebreton F and Willems RJL and Gilmore MS}
}
@article {1664952,
	title = {PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia},
	journal = {Cells},
	volume = {12},
	number = {2},
	year = {2023},
	month = {2023 Jan 13},
	abstract = {Mutations in PDE6D impair the function of its cognate protein, phosphodiesterase 6D (PDE6D), in prenylated protein trafficking towards the ciliary membrane, causing the human ciliopathy Joubert Syndrome (JBTS22) and retinal degeneration in mice. In this study, we purified the prenylated cargo of PDE6D by affinity proteomics to gain insight into PDE6D-associated disease mechanisms. By this approach, we have identified a specific set of PDE6D-interacting proteins that are involved in photoreceptor integrity, GTPase activity, nuclear import, or ubiquitination. Among these interacting proteins, we identified novel ciliary cargo proteins of PDE6D, including FAM219A, serine/threonine-protein kinase NIM1 (NIM1K), and ubiquitin-like protein 3 (UBL3). We show that NIM1K and UBL3 localize inside the cilium in a prenylation-dependent manner. Furthermore, UBL3 also localizes in vesicle-like structures around the base of the cilium. Through affinity proteomics of UBL3, we confirmed its strong interaction with PDE6D and its association with proteins that regulate small extracellular vesicles (sEVs) and ciliogenesis. Moreover, we show that UBL3 localizes in specific photoreceptor cilium compartments in a prenylation-dependent manner. Therefore, we propose that UBL3 may play a role in the sorting of proteins towards the photoreceptor outer segment, further explaining the development of PDE6D-associated retinal degeneration.},
	keywords = {Animals, Cilia, Cyclic Nucleotide Phosphodiesterases, Type 6, Humans, Mice, Protein Transport, Proteins, Retina, Retinal Degeneration},
	issn = {2073-4409},
	doi = {10.3390/cells12020312},
	author = {Faber, Siebren and Letteboer, Stef J F and Junger, Katrin and Butcher, Rossano and Tammana, Trinadh V Satish and van Beersum, Sylvia E C and Ueffing, Marius and Collin, Rob W J and Liu, Qin and Boldt, Karsten and Roepman, Ronald}
}
@article {961686,
	title = {Corneal Resistance to Keratolysis After Collagen Crosslinking With Rose Bengal and Green Light.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {15},
	year = {2016},
	month = {2016 Dec 01},
	pages = {6610-6614},
	abstract = {Purpose: The purpose of this study was to evaluate the resistance to degradation by collagenase A of corneas that have been crosslinked with Rose Bengal and green light (RGX). Methods: The ex vivo crosslinking procedure was performed on enucleated rabbit corneas. Corneas were deepithelialized after applying 30\% alcohol. Corneas were stained with Rose Bengal (RB, 0.1\%) for 2 minutes and then exposed to green light (532 nm) at 0.25 W/cm2 for times to deliver doses of 50, 100, 150, or 200 J/cm2 (n = 5 per group). Five corneas were pretreated with riboflavin solution (0.1\% riboflavin) for 15 minutes and irradiated with ultraviolet A (UVA) light (370 nm, 3 mW/cm2) for 30 minutes. Five corneas underwent only de-epithelialization and were otherwise untreated. Five corneas were stained with RB without light exposure. The central corneas of each group was removed with a 8.5-mm trephine and incubated at 37{\textdegree}C in 0.3\% collagenase A solution. Time to dissolution of each cornea was compared across treatments. Results: Corneas treated with RGX were treated with light fluences of 50, 100, 150, and 200 J/cm2; these corneas dissolved completely at 8.3 {\textpm} 1.2, 11.1 {\textpm} 1.4, 12.4 {\textpm} 1.7, and 15.7 {\textpm} 1.8 hours, respectively. Corneas treated by riboflavin and UVA light dissolved at 15.7 {\textpm} 1.7 hours, and nontreated corneas dissolved at 6.1 {\textpm} 1.3 hours. Corneas treated with only RB (no green light) dissolved at 9.3 {\textpm} 1.7 hours. Compared with the untreated corneas, all of the RB groups and the riboflavin-UVA-treated group of corneas degraded statistically significantly slower than untreated corneas (P \&lt; 0.05). Conclusions: Crosslinking with RGX increased corneal resistance to digestion by collagenase comparable to that produced by riboflavin and UVA treatment.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18764},
	author = {Fadlallah, Ali and Zhu, Hong and Arafat, Samer and Kochevar, Irene and Melki, Samir and Ciolino, Joseph B}
}
@article {1354334,
	title = {Treatment of seronegative spondyloarthropathy-associated uveitis with golimumab: retrospective case series},
	journal = {Clin Exp Ophthalmol},
	volume = {42},
	number = {4},
	year = {2014},
	month = {2014 May-Jun},
	pages = {392-5},
	keywords = {Adult, Antibodies, Monoclonal, Child, Female, Humans, Male, Retrospective Studies, Spondylarthropathies, Treatment Outcome, Tumor Necrosis Factor-alpha, Uveitis, Visual Acuity},
	issn = {1442-9071},
	doi = {10.1111/ceo.12207},
	author = {Faez, Sepideh and Lobo, Ann-Marie and Sobrin, Lucia and Papaliodis, George N}
}
@article {630256,
	title = {Ocular inflammatory disease in patients with polymyalgia rheumatica: A case series and review of the literature.},
	journal = {Clin Rheumatol},
	volume = {35},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {251-8},
	abstract = {Scleritis and uveitis are potentially blinding conditions that can be associated with systemic inflammatory diseases. Polymyalgia rheumatica (PMR) is a common rheumatic disorder of the elderly of uncertain etiology. Although there are a few published reports of scleritis and uveitis in PMR patients, the association of PMR to ocular inflammation has not been well established. The aim of this study is to report a series of PMR patients with scleritis and/or uveitis and review the prior published reports of this potential association. We retrospectively reviewed the medical charts of patients with PMR and scleritis or uveitis who were examined in the Ocular Immunology Service of Massachusetts Eye and Ear Infirmary. We also performed a systematic literature search (PubMed; January 1990 until January 2014) to identify earlier published reports. Seven PMR patients with ocular inflammatory disease (OID) were included in our study: two with scleritis, three with anterior uveitis, and two with panuveitis. The onset of PMR preceded the occurrence of OID in six patients, and in one patient uveitis developed 2\&nbsp;months prior to PMR. Five patients demonstrated a temporal association between flares of PMR and OID. In four patients, OID flares developed during tapering of systemic prednisone prescribed for PMR. Four of the five patients who had relapsing PMR had recurrent or persistent uveitis over the course of follow-up. PMR may be associated with both scleritis and uveitis and should be considered as a possible underlying cause of OID.},
	issn = {1434-9949},
	doi = {10.1007/s10067-014-2558-6},
	author = {Faez, Sepideh and Lobo, Ann-Marie and Unizony, Sebastian H and Stone, John H and Papaliodis, George N and Sobrin, Lucia}
}
@article {1698261,
	title = {Systemic Treatment Reduces Von-Hippel-Lindau-Associated Retinal Capillary Hemangioblastoma},
	journal = {Ophthalmology},
	volume = {130},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {524},
	keywords = {Capillaries, Hemangioblastoma, Humans, Retina, Retinal Neoplasms, von Hippel-Lindau Disease},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.07.007},
	author = {Fairbanks, Aaron M and Hoyek, Sandra and Patel, Nimesh A}
}
@article {1664961,
	title = {Controversies and Disparities in the Management of Age-Related Macular Degeneration},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {134-142},
	abstract = {Age-related macular degeneration is a leading cause of blindness in patients aged 50\&nbsp;years and older. Prior to the 21st century, there were no effective treatments for this devastating disease. However, the last 20\&nbsp;years have heralded the development of treatments for both the nonexudative and exudative forms. The invention of AREDS vitamin supplements and anti-VEGF therapies forever changed the treatment of dry and wet age-related macular degeneration, respectively. The rapid adoption and expansion of these vision preserving treatments has created controversy regarding their cost, burden of administration, development, and use of new technologies, genetic considerations, and observed societal disparities. Many of these controversies and disparities persist today and will require further research to resolve.},
	keywords = {Aged, Angiogenesis Inhibitors, Blindness, Humans, Intravitreal Injections, Middle Aged, Tomography, Optical Coherence, Treatment Outcome, Vascular Endothelial Growth Factor A, Wet Macular Degeneration},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152705},
	author = {Fairbanks, Aaron M and Husain, Deeba}
}
@article {1698361,
	title = {Oblique multi-periscopic prism for field expansion of homonymous hemianopia},
	journal = {Biomed Opt Express},
	volume = {14},
	number = {5},
	year = {2023},
	month = {2023 May 01},
	pages = {2352-2364},
	abstract = {Oblique Fresnel peripheral prisms have been used for field expansion in homonymous hemianopia mobility such as walking and driving. However, limited field expansion, low image quality, and small eye scanning range limit their effectiveness. We developed a new oblique multi-periscopic prism using a cascade of rotated half-penta prisms, which provides 42{\textdegree} horizontal field expansion along with 18{\textdegree} vertical shift, high image quality, and wider eye scanning range. Feasibility and performance of a prototype using 3D-printed module are demonstrated by raytracing, photographic depiction, and Goldmann perimetry with patients with homonymous hemianopia.},
	issn = {2156-7085},
	doi = {10.1364/BOE.485373},
	author = {Falahati, Mojtaba and Kurukuti, Nish Mohith and Vargas-Martin, Fernando and Peli, Eli and Jung, Jae-Hyun}
}
@article {1667699,
	title = {Two siblings with GAPO syndrome: Ophthalmic presentation and histopathologic findings},
	journal = {Ophthalmic Genet},
	volume = {44},
	number = {6},
	year = {2023},
	month = {2023 Dec},
	pages = {598-601},
	abstract = {BACKGROUND: GAPO syndrome (growth retardation, alopecia, pseudoanodontia, optic atrophy) is a rare, autosomal recessive connective tissue disorder with only 60 reported cases. Ophthalmic manifestations vary and include hypertelorism, optic atrophy, and glaucoma. There have been three reported cases of GAPO syndrome with craniosynostosis. MATERIALS/METHODS: We describe two new siblings with GAPO syndrome and craniosynostosis and the first histopathologic analysis of Tenon{\textquoteright}s capsule and extraocular muscle in this syndrome. RESULTS: Both siblings presented with papilledema and V-pattern strabismus in addition to the alopecia, brittle eyelashes, growth retardation, and pseudoanodontia that characterize GAPO syndrome. Cranial vault expansion, though successful, was complicated by lack of distinct periosteal layers, thin dural adherence to bone, and extensive venous bleeding. Tenons encountered during strabismus surgery was inelastic and highly vascular. Histopathological analysis revealed hyalinization of Tenon{\textquoteright}s and a thickened, homogenized, amorphous appearance, similar to the extracellular matrix abnormalities described in skin and other organs Histopathological analysis of extraocular muscle was, in contrast, unremarkable. CONCLUSIONS: GAPO impacts the extracellular matrix of Tenon{\textquoteright}s resulting in inelasticity and hypervascularity. Ophthalmologists should be mindful of these aberrant characteristics when planning surgery in this population.},
	keywords = {Alopecia, Craniosynostoses, Growth Disorders, Humans, Optic Atrophy, Siblings, Strabismus},
	issn = {1744-5094},
	doi = {10.1080/13816810.2023.2175225},
	author = {Falcone, Michelle M and Chang, Yoon-Hee and Lidov, Hart and Stagner, Anna M and Dagi, Linda R}
}
@article {1586172,
	title = {Emerging therapies for amblyopia},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {282-288},
	abstract = {Traditional therapies to treat amblyopia, such as optical correction or occlusion/penalization of the non-amblyopic eye, are efficacious but are not without limitations such as poor adherence and decreased success with increasing age. Recently, there has been an interest in new amblyopia therapies, some using binocular techniques, through a variety of platforms including video games, movies, and virtual reality. Overall, available efficacy results for these treatments are highly variable.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1893765},
	author = {Falcone, Michelle M and Hunter, David G and Gaier, Eric D}
}
@article {509126,
	title = {Association of clusterin (CLU) variants and exfoliation syndrome: An analysis in two Caucasian studies and a meta-analysis.},
	journal = {Exp Eye Res},
	volume = {139},
	year = {2015},
	month = {2015 Oct},
	pages = {115-22},
	abstract = {Exfoliation syndrome (XFS) is an important risk factor for glaucoma (XFG) worldwide. LOXL1 variants are highly associated with XFS in most populations; however, the high frequency of risk alleles in normal individuals and the reversal of risk alleles in different ethnic populations suggest that other factors contribute to XFS pathogenesis. Clusterin (CLU) is an extracellular matrix chaperone that prevents protein aggregation and is highly expressed in ocular tissues affected by XFS. Studies examining common CLU variants for association with XFS have been inconsistent. The purpose of this study was to evaluate CLU variants for association with XFS in two independent datasets from the United States (222 cases and 344 controls) and Israel (92 cases and 102 controls). Seven tag SNPs that captured \&gt;95\% of alleles at r(2) greater than 0.8 across the CLU genomic region were genotyped using TaqMan assays. Genotypes for an additional SNP, rs2279590, were imputed using phased haplotypes of HapMap reference CEU samples. Of the 8 CLU SNPs selected for the study, none were significantly associated with XFS in either case-control group (age and sex adjusted P\&nbsp;\&gt;\&nbsp;0.14 and 0.36, respectively, in the US and Israeli datasets), or when they were meta-analyzed together (age and sex adjusted P\&nbsp;\&gt;\&nbsp;0.13). Haplotype analysis using all 8 SNPs or only the promoter region SNPs also did not show significant associations of CLU with XFS in the combined US and Israeli dataset (P\&nbsp;\&gt;\&nbsp;0.28). Meta-analysis of the data from this study and previous studies in Caucasian populations (1184 cases and 978 controls) resulted in statistically significant association of rs2279590 with XFS (summary OR\&nbsp;=\&nbsp;1.18, 95\% CI: 1.03-1.33, P\&nbsp;=\&nbsp;0.01). Significant association between rs2279590 and XFS was also found in Indian populations (summary OR\&nbsp;=\&nbsp;0.76, 95\% CI: 0.61-0.96; P\&nbsp;=\&nbsp;0.02); however, significant heterogeneity between the Caucasian and Indian populations possibly due to reversal of the risk allele precluded an overall meta-analysis for rs2279590 (Q\&nbsp;=\&nbsp;0.001, I(2)\&nbsp;=\&nbsp;91\%). No significant association was identified for rs3087554 in either Caucasian populations (summary OR\&nbsp;=\&nbsp;0.90, 95\% CI: 0.77-1.05, P\&nbsp;=\&nbsp;0.17) or Indian populations (summary OR\&nbsp;=\&nbsp;0.89, 95\% CI: 0.72-1.10, P\&nbsp;=\&nbsp;0.28), or in both populations combined (1705 cases and 3713 controls; summary OR\&nbsp;=\&nbsp;0.90, 95\% CI: 0.79-1.01, P\&nbsp;=\&nbsp;0.08). Significant heterogeneity precluded the addition of the Japanese data to the meta-analysis for rs3087554 (Q\&nbsp;=\&nbsp;0.006, I(2)\&nbsp;=\&nbsp;87\%). Our results suggest that common CLU variants may contribute to modest XFS risk but even larger datasets are required to confirm these findings.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2015.08.004},
	author = {Fan, Bao J and Pasquale, Louis R and Kang, Jae H and Levkovitch-Verbin, Hani and Haines, Jonathan L and Wiggs, Janey L}
}
@article {1532352,
	title = {Characterization of Clinical and Immune Responses in an Experimental Chronic Autoimmune Uveitis Model},
	journal = {Am J Pathol},
	volume = {191},
	number = {3},
	year = {2021},
	month = {2021 03},
	pages = {425-437},
	abstract = {Autoimmune uveitis is a sight-threatening intraocular inflammatory disease. For \&gt;30 years, the mouse model of experimental autoimmune uveitis has been employed to investigate disease mechanisms and test immunotherapeutic approaches. However, inflammation in this model is self-limited, and does not replicate the chronic, insidious nature prevalent in the human disease. Herein, a robust and reliable model of chronic autoimmune uveitis was developed and characterized in two strains of wild-type mice by modifying interphotoreceptor retinoid-binding protein dose and peptide fragments from conventional experimental autoimmune uveitis models. In both of these murine strains, immunization with our modified protocols resulted in a slowly progressive uveitis, with retinal scars and atrophy observed in the chronic stage by fundoscopy. Optical coherence tomography demonstrated decreased retinal thickness in chronic autoimmune uveitis mice, and electroretinography showed significantly reduced amplitudes of dark-adapted a- and b-waves and light-adapted b-waves. Histologic examination revealed prominent choroiditis with extensive retinal damage. Flow cytometry analysis showed substantially increased numbers of CD44IL-17IFN-γ memory T-helper 17 (Th17) cells in the retina, cervical lymph nodes, inguinal lymph nodes, and spleen. These data establish new modified protocols for inducing chronic uveitis in wild-type mice, and demonstrate a predominant memory Th17 cell response, suggesting an important role for memory Th17 cells in driving chronic inflammation in autoimmune uveitis.},
	keywords = {Animals, Autoimmune Diseases, Chronic Disease, Disease Models, Animal, Immunity, Inflammation, Mice, Mice, Inbred C57BL, Retinal Degeneration, Th17 Cells, Uveitis},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.09.004},
	author = {Fan, Nai-Wen and Li, Joy and Mittal, Sharad K and Foulsham, William and Elbasiony, Elsayed and Huckfeldt, Rachel M and Chauhan, Sunil K and Chen, Yihe}
}
@article {1318860,
	title = {Family-Based Genome-Wide Association Study of South Indian Pedigrees Supports WNT7B as a Central Corneal Thickness Locus},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {6},
	year = {2018},
	month = {2018 May 01},
	pages = {2495-2502},
	abstract = {Purpose: To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. Methods: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Results: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; β = -0.57, 95\% confidence interval [CI]: -0.78 to -0.36; P = 1.7 {\texttimes} 10-7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (β = -3.94, 95\% CI: -5.23 to -2.66; P = 1.7 {\texttimes} 10-9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. Conclusions: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-23536},
	author = {Fan, Bao Jian and Chen, Xueli and Sondhi, Nisha and Sharmila, P Ferdinamarie and Soumittra, Nagasamy and Sripriya, Sarangapani and Sacikala, Srinivasan and Asokan, Rashima and Friedman, David S and Pasquale, Louis R and Gao, X Raymond and Vijaya, Lingam and Bailey, Jessica Cooke and Vitart, Veronique and Macgregor, Stuart and Hammond, Christopher J and Khor, Chiea Chuen and Haines, Jonathan L and George, Ronnie and Wiggs, Janey L and Mexican American Glaucoma Genetic Study; International Glaucoma Genetics Consortium; and NEIGHBORHOOD Consortium}
}
@article {1460357,
	title = {Association of a Primary Open-Angle Glaucoma Genetic Risk Score With Earlier Age at Diagnosis},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Aug 22},
	abstract = {Importance: Genetic variants associated with primary open-angle glaucoma (POAG) are known to influence disease risk. However, the clinical effect of associated variants individually or in aggregate is not known. Genetic risk scores (GRS) examine the cumulative genetic load by combining individual genetic variants into a single measure, which is assumed to have a larger effect and increased power to detect relevant disease-related associations. Objective: To investigate if a GRS that comprised 12 POAG genetic risk variants is associated with age at disease diagnosis. Design, Setting, and Participants: A cross-sectional study included individuals with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. A GRS was formulated using 12 variants known to be associated with POAG, and the alleles associated with increasing risk of POAG were aligned in the case-control sets. In case-only analyses, the association of the GRS with age at diagnosis was analyzed as an estimate of disease onset. Results from cohort-specific analyses were combined with meta-analysis. Data collection started in August 2012 for the NEIGHBOR cohort and in July 2008 for the GLAUGEN cohort and were analyzed starting in March 2018. Main Outcomes and Measures: Association of a 12 single-nucleotide polymorphism POAG GRS with age at diagnosis in individuals with POAG using linear regression. Results: The GLAUGEN study included 976 individuals with POAG and 1140 controls. The NEIGHBOR study included 2132 individuals with POAG and 2290 controls. For individuals with POAG, the mean (SD) age at diagnosis was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. For controls, the mean (SD) age at enrollment was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort. All study participants were European white. The GRS was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95\% CI, 1.21-1.27; P = 3.4 {\texttimes} 10-66). In case-only analyses, each higher GRS unit was associated with a 0.36-year earlier age at diagnosis (β = -0.36; 95\% CI, -0.56 to -0.16; P = 4.0 {\texttimes} 10-4). Individuals in the top 5\% of the GRS had a mean (SD) age at diagnosis of 5.2 (12.8) years earlier than those in the bottom 5\% GRS (61.4 [12.7] vs 66.6 [12.9] years; P = 5.0 {\texttimes} 10-4). Conclusions and Relevance: A higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis. On average, individuals with POAG with the highest GRS had 5.2-year earlier age at diagnosis of disease. These results suggest that a GRS that comprised genetic variants associated with POAG could help identify patients with risk of earlier disease onset impacting screening and therapeutic strategies.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.3109},
	author = {Fan, Bao Jian and Bailey, Jessica Cooke and Igo, Rob P and Kang, Jae H and Boumenna, Tahani and Brilliant, Murray H and Budenz, Donald L and Fingert, John H and Gaasterland, Terry and Gaasterland, Douglas and Hauser, Michael A and Kraft, Peter and Lee, Richard K and Lichter, Paul R and Liu, Yutao and Moroi, Syoko E and Myers, Jonathan S and Pericak-Vance, Margaret A and Realini, Anthony and Rhee, Douglas J and Richards, Julia E and Ritch, Robert and Schuman, Joel S and Scott, William K and Singh, Kuldev and Sit, Arthur J and Vollrath, Douglas and Weinreb, Robert N and Wollstein, Gadi and Zack, Donald J and Haines, Jonathan L and Pasquale, Louis R and Wiggs, Janey L}
}
@article {1511502,
	title = {The role of Th17 immunity in chronic ocular surface disorders},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 May 26},
	abstract = {Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-γ in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.05.009},
	author = {Fan, Nai-Wen and Dohlman, Thomas H and Foulsham, William and McSoley, Matthew and Singh, Rohan Bir and Chen, Yihe and Dana, Reza}
}
@article {1638563,
	title = {Autoreactive memory Th17 cells are principally derived from T-bet+RORγt+ Th17/1 effectors},
	journal = {J Autoimmun},
	volume = {129},
	year = {2022},
	month = {2022 May},
	pages = {102816},
	abstract = {Effector Th17\&nbsp;cells, including IFN-γ-IL-17+ (eTh17) and IFN-γ+IL-17+ (eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17\&nbsp;cells (mTh17), which sustain chronic inflammation in autoimmune diseases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease. Our results show that adoptive transfer of Tbx21-/- CD4+ T cells or conditional deletion of Tbx21 in Th17\&nbsp;cells leads to diminished eTh17/1 in acute phase and functionally compromised mTh17 in chronic phase. Further, adoptive transfer of disease-specific eTh17/1, but not eTh17, leads to generation of mTh17 and sustained ocular inflammation. Collectively, our data demonstrate that T-bet-dependent eTh17/1\&nbsp;cells generated during the acute inflammation are the principal effector precursors of pathogenic mTh17\&nbsp;cells that sustain the chronicity of autoimmune inflammation.},
	keywords = {Autoimmune Diseases, Humans, Inflammation, Interferon-gamma, Interleukin-17, Nuclear Receptor Subfamily 1, Group F, Member 3, Th1 Cells, Th17 Cells},
	issn = {1095-9157},
	doi = {10.1016/j.jaut.2022.102816},
	author = {Fan, Nai-Wen and Wang, Shudan and Ortiz, Gustavo and Chauhan, Sunil K and Chen, Yihe and Dana, Reza}
}
@article {1688321,
	title = {Long-lived autoreactive memory CD4+ T cells mediate the sustained retinopathy in chronic autoimmune uveitis},
	journal = {FASEB J},
	volume = {37},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {e22855},
	abstract = {Chronic uveitis comprises heterogeneous clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. The management of chronic uveitis is challenging with the limited availability of efficacious treatments, and the underlying mechanisms mediating disease chronicity remain poorly understood as the majority of experimental data are derived from the acute phase of the disease (the first 2-3 weeks post-induction). Herein, we investigated the key cellular mechanisms underlying chronic intraocular inflammation using our recently established murine model of chronic autoimmune uveitis. We demonstrate unique long-lived CD44hi IL-7R+ IL-15R+ CD4+ memory T cells in both retina and secondary lymphoid organs after 3 months postinduction of autoimmune uveitis. These memory T cells functionally exhibit antigen-specific proliferation and activation in response to retinal peptide stimulation in vitro. Critically, these effector-memory T cells are capable of effectively trafficking to the retina and accumulating in the local tissues secreting both IL-17 and IFN-γ upon adoptively transferred, leading to retinal structural and functional damage. Thus, our data reveal the critical uveitogenic functions of memory CD4+ T cells in sustaining chronic intraocular inflammation, suggesting that memory T cells can be a novel and promising therapeutic target for treating chronic uveitis in future translational studies.},
	keywords = {Animals, Autoimmune Diseases, CD4-Positive T-Lymphocytes, Disease Models, Animal, Humans, Inflammation, Mice, Retinal Diseases, Uveitis},
	issn = {1530-6860},
	doi = {10.1096/fj.202202164R},
	author = {Fan, Nai-Wen and Zhu, Qiurong and Wang, Shudan and Ortiz, Gustavo and Huckfeldt, Rachel M and Chen, Yihe}
}
@article {1016036,
	title = {Enhanced Diagnostic Capability for Glaucoma of 3-Dimensional Versus 2-Dimensional Neuroretinal Rim Parameters Using Spectral Domain Optical Coherence Tomography},
	journal = {J Glaucoma},
	volume = {26},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {450-458},
	abstract = {PURPOSE: To compare the diagnostic capability of 3-dimensional (3D) neuroretinal rim parameters with existing 2-dimensional (2D) neuroretinal and retinal nerve fiber layer (RNFL) thickness rim parameters using spectral domain optical coherence tomography (SD-OCT) volume scans. MATERIALS AND METHODS: Design: Institutional prospective pilot study. STUDY POPULATION: 65 subjects (35 open-angle glaucoma patients, 30 normal patients). OBSERVATION PROCEDURES: One eye of each subject was included. SD-OCT was used to obtain 2D RNFL thickness values and 5 neuroretinal rim parameters [ie, 3D minimum distance band (MDB) thickness, 3D Bruch{\textquoteright}s membrane opening-minimum rim width (BMO-MRW), 3D rim volume, 2D rim area, and 2D rim thickness]. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve values, sensitivity, and specificity. RESULTS: Comparing all 3D with all 2D parameters, 3D rim parameters (MDB, BMO-MRW, rim volume) generally had higher area under the receiver operating characteristic curve values (range, 0.770 to 0.946) compared with 2D parameters (RNFL thickness, rim area, rim thickness; range, 0.678 to 0.911). For global region analyses, all 3D rim parameters (BMO-MRW, rim volume, MDB) were equal to or better than 2D parameters (RNFL thickness, rim area, rim thickness; P-values from 0.023 to 1.0). Among the three 3D rim parameters (MDB, BMO-MRW, and rim volume), there were no significant differences in diagnostic capability (false discovery rate \&gt;0.05 at 95\% specificity). CONCLUSIONS: 3D neuroretinal rim parameters (MDB, BMO-MRW, and rim volume) demonstrated better diagnostic capability for primary and secondary open-angle glaucomas compared with 2D neuroretinal parameters (rim area, rim thickness). Compared with 2D RNFL thickness, 3D neuroretinal rim parameters have the same or better diagnostic capability.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000647},
	author = {Fan, Kenneth C and Tsikata, Edem and Khoueir, Ziad and Simavli, Huseyin and Guo, Rong and A de Luna, Regina and Pandit, Sumir and Que, Christian J and de Boer, Johannes F and Chen, Teresa C}
}
@article {1658665,
	title = {Doxorubicin-Loaded Extracellular Vesicles Enhance Tumor Cell Death in Retinoblastoma},
	journal = {Bioengineering (Basel)},
	volume = {9},
	number = {11},
	year = {2022},
	month = {2022 Nov 10},
	abstract = {Chemotherapy is often used to treat retinoblastoma; however, this treatment method has severe systemic adverse effects and inadequate therapeutic effectiveness. Extracellular vesicles (EVs) are important biological information carriers that mediate local and systemic cell-to-cell communication under healthy and pathological settings. These endogenous vesicles have been identified as important drug delivery vehicles for a variety of therapeutic payloads, including doxorubicin (Dox), with significant benefits over traditional techniques. In this work, EVs were employed as natural drug delivery nanoparticles to load Dox for targeted delivery to retinoblastoma human cell lines (Y-79). Two sub-types of EVs were produced from distinct breast cancer cell lines (4T1 and SKBR3) that express a marker that selectively interacts with retinoblastoma cells and were loaded with Dox, utilizing the cells{\textquoteright} endogenous loading machinery. In vitro, we observed that delivering Dox with both EVs increased cytotoxicity while dramatically lowering the dosage of the drug. Dox-loaded EVs, on the other hand, inhibited cancer cell growth by activating caspase-3/7. Direct interaction of EV membrane moieties with retinoblastoma cell surface receptors resulted in an effective drug delivery to cancer cells. Our findings emphasize the intriguing potential of EVs as optimum methods for delivering Dox to retinoblastoma.},
	issn = {2306-5354},
	doi = {10.3390/bioengineering9110671},
	author = {Farhat, Wissam and Yeung, Vincent and Kahale, Francesca and Parekh, Mohit and Cortinas, John and Chen, Lin and Ross, Amy E and Ciolino, Joseph B}
}
@article {1653581,
	title = {Advances in biomaterials for the treatment of retinoblastoma},
	journal = {Biomater Sci},
	volume = {10},
	number = {19},
	year = {2022},
	month = {2022 Sep 27},
	pages = {5391-5429},
	abstract = {Retinoblastoma is the most common primary intraocular malignancy in children. Although traditional chemotherapy has shown some success in retinoblastoma management, there are several shortcomings to this approach, including inadequate pharmacokinetic parameters, multidrug resistance, low therapeutic efficiency, nonspecific targeting, and the need for adjuvant therapy, among others. The revolutionary developments in biomaterials for drug delivery have enabled breakthroughs in cancer management. Today, biomaterials are playing a crucial role in developing more efficacious retinoblastoma treatments. The key goal in the evolution of drug delivery biomaterials for retinoblastoma therapy is to resolve delivery-associated obstacles and lower nonlocal exposure while ameliorating certain adverse effects. In this review, we will first delve into the historical perspective of retinoblastoma with a focus on the classical treatments currently used in clinics to enhance patients{\textquoteright} quality of life and survival rate. As we move along, we will discuss biomaterials for drug delivery applications. Various aspects of biomaterials for drug delivery will be dissected, including their features and recent advances. In accordance with the current advances in biomaterials, we will deliver a synopsis on the novel chemotherapeutic drug delivery strategies and evaluate these approaches to gain new insights into retinoblastoma treatment.},
	keywords = {Biocompatible Materials, Child, Combined Modality Therapy, Humans, Quality of Life, Retinal Neoplasms, Retinoblastoma},
	issn = {2047-4849},
	doi = {10.1039/d2bm01005d},
	author = {Farhat, Wissam and Yeung, Vincent and Ross, Amy and Kahale, Francesca and Boychev, Nikolay and Kuang, Liangju and Chen, Lin and Ciolino, Joseph B}
}
@article {1709786,
	title = {Placebos in pediatrics: A cross-sectional survey investigating physicians{\textquoteright} perspectives},
	journal = {J Psychosom Res},
	volume = {172},
	year = {2023},
	month = {2023 Sep},
	pages = {111421},
	abstract = {OBJECTIVE: Placebo responses are significantly higher in children than in adults, suggesting a potential underused treatment option in pediatric care. To facilitate the clinical translation of these beneficial effects, we explored physicians{\textquoteright} current practice, opinions, knowledge, and likelihood of recommending placebos in the future. METHODS: A cross-sectional web-based survey administered by REDCap was conducted at Boston Children{\textquoteright}s Hospital between October 2021 and March 2022. Physicians (n\&nbsp;=\&nbsp;1157) were invited to participate through an email containing a link to a 23-item survey designed to assess physicians{\textquoteright} attitudes and perceptions towards the clinical use of placebo in pediatrics. RESULTS: From 207 (18\%) returned surveys, 109 (9\%) were fully completed. Most respondents (79\%) believed that enhancing the therapeutic components that contribute to the placebo response may be a way of improving pediatric care. However, whereas most (62\%) found placebo treatments permissible, only one-third reported recommending them. In pediatrics, placebos are typically introduced as a medicine that "might help" (43\%). The most common treatments recommended to enhance placebo effects are physical therapy, vitamins, and over-the-counter analgesics. Physicians most frequently recommend placebos for occasional pain, headaches, and anxiety disorders. Finally, the great majority of physicians (87\%) stated they would be more likely to recommend placebo treatments if there were safety and ethical guidelines for open-label placebos. CONCLUSIONS: Placebo treatments seem permissible to physicians in pediatric care, but the development of safety and ethical guidelines may be necessary before physicians systematically incorporate the benefits of the placebo effect in pediatrics.},
	keywords = {Attitude of Health Personnel, Child, Cross-Sectional Studies, Humans, Pediatrics, Physicians, Practice Patterns, Physicians{\textquoteright}, Surveys and Questionnaires},
	issn = {1879-1360},
	doi = {10.1016/j.jpsychores.2023.111421},
	author = {Faria, Vanda and Talbert, Cameron and Goturi, Nathan and Borsook, David and Lebel, Alyssa and Kaptchuk, Ted J and Kirsch, Irving and Kelley, John M and Moulton, Eric A}
}
@article {1430526,
	title = {Incidence of Age-Related Macular Degeneration in the Central Region of Portugal: The Coimbra Eye Study - Report 5},
	journal = {Ophthalmic Res},
	year = {2019},
	month = {2019 Mar 01},
	pages = {1-10},
	abstract = {PURPOSE: To describe the 6.5-year incidence and progression of age-related macular degeneration (AMD) in a coastal town of central Portugal. METHODS: Population-based cohort study. Participants underwent standardized interviews and ophthalmological examination. Color fundus photographs were graded according to the International Classification and Grading System for AMD and ARM. The crude and age-standardized incidence of early and late AMD was calculated, and progression was analyzed. RESULTS: The 6.5-year cumulative incidence of early AMD was 10.7\%, and of late AMD it was 0.8\%. The incidence of early AMD was 7.2, 13.1 and 17.7\% for participants aged 55-64, 65-74 and 75-84 years (p \&lt; 0.001). The late AMD incidence was 0.3, 0.9 and 2.8\% for the corresponding age groups (p = 0.003). The age-standardized incidence was 10.8\% (95\% CI, 10.74-10.80\%) for early and 1.0\% (95\% CI, 1.00-1.02\%) for late AMD. The incidence of both neovascular AMD and geographic atrophy was 0.4\%. Progression occurred in 17.2\% of patients. CONCLUSION: The early AMD incidence in a coastal town of central Portugal was found to be similar to that of major epidemiological studies of European-descent populations; however, the incidence of late AMD was lower, and further analysis on risk factors will be conducted.},
	issn = {1423-0259},
	doi = {10.1159/000496393},
	author = {Farinha, Cl{\'a}udia Virg{\'\i}nia Louro and Cachulo, Maria Luz and Alves, Dalila and Pires, Isabel and Marques, Jo{\~a}o Pedro and Barreto, Patr{\'\i}cia and Nunes, Sandrina and Costa, Jos{\'e} and Martins, Am{\'e}lia and Sobral, Isa and La{\'\i}ns, In{\^e}s and Figueira, Jo{\~a}o and Ribeiro, Lu{\'\i}sa and Cunha-Vaz, Jos{\'e} and Silva, Rufino}
}
@article {1511487,
	title = {Age-Related Macular Degeneration Staging by Color Fundus Photography vs. Multimodal Imaging-Epidemiological Implications ()},
	journal = {J Clin Med},
	volume = {9},
	number = {5},
	year = {2020},
	month = {2020 May 02},
	abstract = {Epidemiology of age-related macular degeneration (AMD) is based on staging systems relying on color fundus photography (CFP). We aim to compare AMD staging using CFP to multimodal imaging with optical coherence tomography (OCT), infra-red (IR), and fundus autofluorescence (FAF), in a large cohort from the Epidemiologic AMD Coimbra Eye Study. All imaging exams from the participants of this population-based study were classified by a central reading center. CFP images were graded according to the International Classification and Grading System for AMD and staged with Rotterdam classification. Afterward, CFP images were reviewed with OCT, IR, and FAF and stage update was performed if necessary. Early and late AMD prevalence was compared in a total of 1616 included subjects. In CFP-based grading, the prevalence was 14.11\% for early AMD ( = 228) and 1.05\% ( = 17) for late AMD, nine cases (0.56\%) had neovascular AMD (nAMD) and eight (0.50\%) geographic atrophy (GA). Using multimodal grading, the prevalence increased to 14.60\% for early AMD ( = 236) and 1.61\% ( = 26) for late AMD, with 14 cases (0.87\%) of nAMD and 12 (0.74\%) of GA. AMD staging was more accurate with the multimodal approach and this was especially relevant for late AMD. We propose that multimodal imaging should be adopted in the future to better estimate and compare epidemiological data in different populations.},
	issn = {2077-0383},
	doi = {10.3390/jcm9051329},
	author = {Farinha, Cl{\'a}udia and Cachulo, Maria Luz and Coimbra, Rita and Alves, Dalila and Nunes, Sandrina and Pires, Isabel and Marques, Jo{\~a}o Pedro and Costa, Jos{\'e} and Martins, Am{\'e}lia and Sobral, Isa and Barreto, Patr{\'\i}cia and La{\'\i}ns, In{\^e}s and Figueira, Jo{\~a}o and Ribeiro, Luisa and Cunha-Vaz, Jos{\'e} and Silva, Rufino}
}
@article {303931,
	title = {Mutations in pre-mRNA processing factors 3, 8, and 31 cause dysfunction of the retinal pigment epithelium.},
	journal = {Am J Pathol},
	volume = {184},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {2641-52},
	abstract = {Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31 (PRPF3, PRPF8, and PRPF31) cause nonsyndromic dominant retinitis pigmentosa in humans, an inherited retinal degeneration. It is unclear what mechanisms, or which cell types of the retina, are affected. Transgenic mice with the human mutations in these genes display late-onset morphological changes in the retinal pigment epithelium (RPE). To determine whether the observed morphological changes are preceded by abnormal RPE function, we investigated its phagocytic function in Prpf3(T494M/T494M), Prpf8(H2309P/H2309P), and Prpf31(+/-) mice. We observe decreased phagocytosis in primary RPE cultures from mutant mice, and this is replicated by shRNA-mediated knockdown of PRPF31 in human ARPE-19 cells. The diurnal rhythmicity of phagocytosis is almost lost, indicated by the marked attenuation of the phagocytic burst 2 hours after light onset. The strength of adhesion between RPE apical microvilli and photoreceptor outer segments also declined during peak adhesion in all mutants. In all models, at least one of the receptors involved in binding and internalization of shed photoreceptor outer segments was subjected to changes in localization. Although the mechanism underlying these changes in RPE function is yet to be elucidated, these data are consistent with the mouse RPE being the primary cell affected by mutations in the RNA splicing factors, and these changes occur at an early age.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2014.06.026},
	author = {Farkas, Michael H and Lew, Deborah S and Sousa, Maria E and Bujakowska, Kinga and Chatagnon, Jonathan and Bhattacharya, Shomi S and Pierce, Eric A and Nandrot, Emeline F}
}
@article {1363276,
	title = {Transcriptome analyses of the human retina identify unprecedented transcript diversity and 3.5 Mb of novel transcribed sequence via significant alternative splicing and novel genes},
	journal = {BMC Genomics},
	volume = {14},
	year = {2013},
	month = {2013 Jul 18},
	pages = {486},
	abstract = {BACKGROUND: The retina is a complex tissue comprised of multiple cell types that is affected by a diverse set of diseases that are important causes of vision loss. Characterizing the transcripts, both annotated and novel, that are expressed in a given tissue has become vital for understanding the mechanisms underlying the pathology of disease. RESULTS: We sequenced RNA prepared from three normal human retinas and characterized the retinal transcriptome at an unprecedented level due to the increased depth of sampling provided by the RNA-seq approach. We used a non-redundant reference transcriptome from all of the empirically-determined human reference tracks to identify annotated and novel sequences expressed in the retina. We detected 79,915 novel alternative splicing events, including 29,887 novel exons, 21,757 3{\textquoteright} and 5{\textquoteright} alternate splice sites, and 28,271 exon skipping events. We also identified 116 potential novel genes. These data represent a significant addition to the annotated human transcriptome. For example, the novel exons detected increase the number of identified exons by 3\%. Using a high-throughput RNA capture approach to validate 14,696 of these novel transcriptome features we found that 99\% of the putative novel events can be reproducibly detected. Further, 15-36\% of the novel splicing events maintain an open reading frame, suggesting they produce novel protein products. CONCLUSIONS: To our knowledge, this is the first application of RNA capture to perform large-scale validation of novel transcriptome features. In total, these analyses provide extensive detail about a previously uncharacterized level of transcript diversity in the human retina.},
	keywords = {Adult, Alternative Splicing, Computational Biology, DNA-Binding Proteins, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Association Studies, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Molecular Sequence Annotation, Neoplasm Proteins, Organ Specificity, Reproducibility of Results, Retina, RNA Isoforms, Transcriptome},
	issn = {1471-2164},
	doi = {10.1186/1471-2164-14-486},
	author = {Farkas, Michael H and Grant, Gregory R and White, Joseph A and Sousa, Maria E and Consugar, Mark B and Pierce, Eric A}
}
@article {382571,
	title = {RNA-Seq: Improving Our Understanding of Retinal Biology and Disease.},
	journal = {Cold Spring Harb Perspect Med},
	year = {2015},
	month = {2015 Feb 26},
	abstract = {Over the past several years, rapid technological advances have allowed for a dramatic increase in our knowledge and understanding of the transcriptional landscape, because of the ability to study gene expression in greater depth and with more detail than previously possible. To this end, RNA-Seq has quickly become one of the most widely used methods for studying transcriptomes of tissues and individual cells. Unlike previously favored analysis methods, RNA-Seq is extremely high-throughput, and is not dependent on an annotated transcriptome, laying the foundation for novel genetic discovery. Additionally, RNA-Seq derived transcriptomes provide a basis for widening the scope of research to identify potential targets in the treatment of retinal disease.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a017152},
	author = {Farkas, Michael H and Au, Elizabeth D and Sousa, Maria E and Pierce, Eric A}
}
@article {1364604,
	title = {Transcriptome analyses to investigate the pathogenesis of RNA splicing factor retinitis pigmentosa},
	journal = {Adv Exp Med Biol},
	volume = {723},
	year = {2012},
	month = {2012},
	pages = {519-25},
	keywords = {Humans, Retinitis Pigmentosa, RNA Precursors, RNA Splicing, RNA-Binding Proteins, Transcriptome},
	issn = {0065-2598},
	doi = {10.1007/978-1-4614-0631-0_65},
	author = {Farkas, Michael H and Grant, Greg R and Pierce, Eric A}
}
@article {1125291,
	title = {Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older},
	journal = {Am J Ophthalmol},
	year = {2017},
	month = {2017 Jul 10},
	abstract = {PURPOSE: To provide current estimates of the prevalence of diagnosed dry eye disease (DED) and associated demographics among US adults aged >=18 years. DESIGN: Cross-sectional, population-based survey. METHODS: Data were analyzed from 75,000 participants in the 2013 National Health and Wellness Survey to estimate prevalence/risk of diagnosed DED overall, and by age, sex, insurance, and other demographic factors. We weighted the observed DED prevalence to project estimates to the US adult population and examined associations between demographic factors and DED using multivariable logistic regression. RESULTS: Based on weighted estimates, 6.8\% of the US adult population was projected to have diagnosed DED (\~{}16.4 million people). Prevalence increased with age (18-34 years: 2.7\%; >=75 years: 18.6\%) and was higher among women (8.8\%; \~{}11.1 million) than men (4.5\%; \~{}5.3 million). After adjustment, there were no substantial differences in prevalence/risk of diagnosed DED by race, education, or US census region. However, there was higher risk of diagnosed DED among those aged 45-54 years (odds ratio [OR]: 1.95; 95\% confidence interval [CI]: 1.74-2.20) and >=75 years (OR: 4.95; 95\% CI: 4.26-5.74), vs those aged 18-34 years. Risk was also higher among women vs men (OR: 2.00; 95\% CI: 1.88-2.13) and insured vs uninsured participants (OR: 2.12; 95\% CI: 1.85-2.43 for those on government and private insurance vs none). CONCLUSIONS: We estimate that \&gt;16 million US adults have diagnosed DED. Prevalence is higher among women than men, increases with age, and is notable among those aged 18-34 years.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.06.033},
	author = {Farrand, Kimberly F and Fridman, Moshe and Stillman, Ipek {\"O}zer and Schaumberg, Debra A}
}
@article {1483614,
	title = {Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {36},
	number = {4},
	year = {2020},
	month = {2020 Jul/Aug},
	pages = {385-389},
	abstract = {PURPOSE: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery. METHODS: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately. RESULTS: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42\%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12\% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5. CONCLUSIONS: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001565},
	author = {Fay, Aaron and Nallasamy, Nambi and Allen, Richard C and Bernardini, Francesco P and Bilyk, Jurij R and Cockerham, Kimberly and Cruz, Antonio Augusto and Devoto, Martin and Peter J Dolman and Dutton, Jonathan J and Jordan, David R and Kersten, Robert and Kim, Yoon-Duck and Lucarelli, Mark J and McNab, Alan A and Mombaerts, Ilse and Mourits, Maarten and Nerad, Jeffrey and Perry, Julian D and Rose, Geoffrey and Saeed, Peerooz and Seah, Lay Leng and Selva, Dinesh and Sivak-Callcott, Jennifer and Strianese, Diego and Verity, David H and Orbital Society}
}
@article {1363277,
	title = {Prophylactic postoperative antibiotics for enucleation and evisceration},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {4},
	year = {2013},
	month = {2013 Jul-Aug},
	pages = {281-5},
	abstract = {PURPOSE: To investigate the necessity and usefulness of prophylactic postoperative antibiotics in patients undergoing enucleation or ocular evisceration. METHODS: A retrospective, multicenter, comparative case series was designed. After obtaining Institutional Review Board authorization, a medical records{\textquoteright} review was conducted. Demographics, indication for surgery, surgical technique, postoperative antibiotic dosing, and postoperative course were evaluated. Records were grouped according to antibiotic protocols, and presence or absence of postoperative wound infection (orbital cellulitis) was recorded. Rates of postoperative infection were analyzed statistically. RESULTS: Between 1996 and 2011, 666 evisceration or enucleation surgeries were conducted at 4 institutions. Six hundred forty-eight records were available for analysis, of which 4 were excluded due to insufficient follow-up data. All the remaining 644 patients received a single, perioperative, intravenous dose of antibiotics. Five hundred seventy-eight patients (90\%) received an orbital implant, while 66 (10\%) did not. Three hundred eighty-one patients (59\%) received postoperative antibiotics, and 263 patients (41\%) did not. Two cases were identified with signs suggestive of infection, but no culture-positive infections were found, and no patient was admitted to the hospital for management. Of the 2 suspicious cases, 1 was found in the group that received postoperative antibiotics (group 1) and 1 in the group that did not receive postoperative antibiotics (group 2). No statistically significant difference in postoperative infection rate was noted between the 2 groups (p=0.52). While patients with infectious indications for surgery were more likely to receive postoperative antibiotics (p\&lt;0.001), there was no statistically significant difference in rates of infection among patients with infectious indications for surgery based on receiving or not receiving postoperative antibiotics (p=0.79), and no patients with infectious indications for surgery not receiving postoperative antibiotics developed a postoperative infection. CONCLUSIONS: This study demonstrates the clinical safety of withholding postoperative prophylactic antibiotics in orbital surgery even when implanting alloplastic material in a sterile field. Furthermore, Centers for Disease Control and Prevention guidelines mandate cessation of postoperative antibiotics within 24 hours of surgery. Surgeons are cautioned not to generalize these results to nonsterile surgery such as sinonasal or nasolacrimal surgery.},
	keywords = {Administration, Oral, Adult, Aged, Anti-Bacterial Agents, Antibiotic Prophylaxis, Eye Enucleation, Eye Evisceration, Eye Infections, Bacterial, Female, Humans, Male, Middle Aged, Postoperative Care, Postoperative Complications, Retrospective Studies, Surgical Wound Infection},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e3182916674},
	author = {Fay, Aaron and Nallasamy, Nambi and Nallassamy, Nambi and Pemberton, John D and Callahan, Allison and Wladis, Edward J and Nguyen, John and Durand, Marlene L and New England Oculoplastics Society Study Group}
}
@book {966016,
	title = {Diseases and Disorders of the Orbit and Ocular Adnexa, 1st Edition},
	year = {2016},
	pages = {744},
	publisher = {Elsevier},
	organization = {Elsevier},
	edition = {1},
	abstract = {Drawing from the knowledge and expertise of more than 70 contributing international experts,\&nbsp;Diseases and Disorders of the Orbit and Ocular Adnexa\&nbsp;thoroughly covers the\&nbsp;state of the art in orbital and periocular disease from the perspective of a variety of specialties.\&nbsp;Clearly written and profusely illustrated, it covers the clinical presentation, pathophysiology, natural history, and management alternatives of disease processes affecting the orbit, eyelids, lacrimal system, and upper face. With a singular focus on the diagnosis and management of orbital and ocular adnexal disease, this authoritative text gives you the information you need to\&nbsp;excel both in practice and on exams\&nbsp;in the specialty of ophthalmic plastic and reconstructive surgery.Key FeaturesOffers an\&nbsp;in-depth and thorough approach\&nbsp;to the pathophysiology of oculoplastics and orbital disease, incorporating the perspectives of numerous specialties - all in\&nbsp;one convenient volume.Uses an\&nbsp;easy-to-follow, templated format\&nbsp;throughout so you can find what you need quickly.Covers\&nbsp;new information not included in other texts,\&nbsp;such as antibody testing in dysthyroid conditions and a rapidly emerging array of targeted immunosuppressive medications for the treatment of inflammatory orbital disease.Includes\&nbsp;hot topics\&nbsp;such as the classification and management of orbital inflammatory disease; vascular neoplasms and malformations; periocular dermatology; burn management; facial paralytic disease; and the pathogenesis, evaluation and management of lymphoproliferative disease.Features\&nbsp;more than 1,200 high-quality clinical, imaging, and histological illustrations\&nbsp;that provide clear visual examples of orbital disease.Written by an\&nbsp;international team of experts from five continents\&nbsp;(across multiple specialties including ophthalmology, dermatology, burn management, plastic surgery, otolaryngology, endocrinology, and pathology) led by Dr. Aaron Fay and Dr. Peter J. Dolman.Expert Consult{\texttrademark} eBook version included with purchase.\&nbsp;This\&nbsp;enhanced eBook experience\&nbsp;allows you to search all of the text, figures, and references from the book on a variety of devices.Author Information By\&nbsp;Aaron Fay, MD, Assistant Professor, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA and\&nbsp;Peter J Dolman, MD, FRCSC , Clinical Professor, Division Head of Oculoplastics and Orbit; Director of Fellowship Programmes, Department of Ophthalmology, University of British Columbia, Vancouver, BC, Canada\&nbsp;},
	author = {Fay, Aaron and Peter J Dolman}
}
@article {416866,
	title = {Multinational Comparison of Prophylactic Antibiotic Use for Eyelid Surgery.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {7},
	year = {2015},
	month = {2015 Jul 1},
	pages = {778-84},
	abstract = {IMPORTANCE: Antibiotic stewardship is important in controlling resistance, adverse reactions, and cost. The literature regarding antibiotic use for eyelid surgery is lacking. OBJECTIVES: To determine standard care and assess factors influencing antibiotic prescribing practices for eyelid surgery. DESIGN, SETTING, AND PARTICIPANTS: A survey study was conducted from February 2, 2014, to March 24, 2014. The survey was distributed to 2397 oculoplastic surgeons in private and academic oculoplastic surgery practices in 43 countries. All surgeons were members of ophthalmic plastic and reconstructive surgery societies. Data were analyzed by geographic location. Linear regression was performed to quantify contributions to rates of prescribing postoperative antibiotics for routine eyelid surgical procedures. MAIN OUTCOMES AND MEASURES: Rates of prescribing prophylactic intravenous, oral, and topical antibiotics as well as factors that influence surgeons{\textquoteright} prescribing practices. RESULTS: A total of 782 responses were received from 2397 surgeons (average response rate, 36.7\%; 2.5\% margin of error) from 43 countries. Topical antibiotic use was common in all regions (85.2\%). Perioperative intravenous antibiotic use was uncommon in all regions (13.5\%). Geographic location was the greatest predictor of antibiotic prescribing practices (range, 2.9\% in the United Kingdom to 86.7\% in India; mean, 24\%). Within Europe, Italy had the highest rate of antibiotic prescriptions for eyelid surgery (41.7\%) and the United Kingdom had the lowest rate (2.9\%.) In South America, Venezuela had the highest rate of antibiotic prescriptions for eyelid surgery (83.3\%) and Chile had the lowest rate (0\%). The practice locations that were associated with routinely prescribing postoperative oral antibiotics were India (odds ratio [OR], 15.83; 95\% CI, 4.85-51.68; P \&lt; .001), Venezuela (OR, 13.47; 95\% CI, 1.43-127.19; P = .02), and Southeast Asia (OR, 2.80; 95\% CI, 1.15-6.84; P = .02). Conversely, practice location in the United Kingdom (OR, 0.048; 95\% CI, 0.0063-0.37; P = .004), Australia and New Zealand (OR, 0.15; 95\% CI, 0.033-0.67; P = .01), and the United States and Canada (OR, 0.41; 95\% CI, 0.23-0.72; P = .002) were associated with decreased rates of postoperative oral antibiotic use. Surgeons{\textquoteright} concern for allergic reactions was associated with decreased rates of prescribing antibiotics (OR, 0.34; 95\% CI, 0.23-0.49; P \&lt; .001), while surgeons{\textquoteright} concern for infection was associated with increased rates of prescribing antibiotics (OR 1.80; 95\% CI, 1.45-2.23; P \&lt; .001). CONCLUSIONS AND RELEVANCE: These results from members of ophthalmic plastic and reconstructive surgery societies confirm that antibiotic prescribing practices for routine eyelid surgical procedures vary widely throughout the world. No standard of care has been established that would require the routine use of postoperative prophylactic antibiotics following eyelid surgery.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.0789},
	author = {Fay, Aaron and Nallasamy, Nambi and Bernardini, Francesco and Wladis, Edward J and Durand, Marlene L and Devoto, Martin H and Meyer, Dale and Hartstein, Morris and Honavar, Santosh and Osaki, Midori H and Osaki, Tammy H and Santiago, Yvette M and Sales-Sanz, Marco and Vadala, Giuseppe and Verity, David}
}
@article {1364605,
	title = {A modified levine palpebral spring for the treatment of myogenic ptosis},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {28},
	number = {5},
	year = {2012},
	month = {2012 Sep-Oct},
	pages = {372-5},
	abstract = {PURPOSE: Surgical treatment of myogenic ptosis usually requires a form of frontalis suspension. Complications can include entropion, headache, contour abnormalities, and poor eyelid excursion. The Levine palpebral spring has been used successfully to augment eyelid closure in more than 2,000 patients. The authors present a modified Levine spring to correct ptosis in a patient with poor levator function. METHODS: Interventional case report. A 55-year-old man with profound myogenic ptosis was treated with bilateral modified Levine palpebral springs. Eyelid position, contour and excursion, blink reflex, lagophthalmos, and ocular surface were evaluated. RESULTS: The Levine palpebral spring functioned well to open both eyelids. Margin reflex distance improved from -3 mm to 3 m postoperatively. Excellent contour and excursion were observed. Orbicularis action, including blink reflex, was preserved, and ocular surface was not compromised. CONCLUSION: The modified Levine palpebral spring is an alternative to frontalis suspension in treating select patients with eyelid ptosis with poor levator function.},
	keywords = {Alloys, Blepharoplasty, Blepharoptosis, Humans, Male, Middle Aged, Oculomotor Muscles, Radiography},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e318263ded7},
	author = {Fay, Aaron and Santiago, Yvette Marie B}
}
@article {1439848,
	title = {Pediatric Intraocular Pressure Measurements: Tonometers, Central Corneal Thickness, and Anesthesia},
	journal = {Surv Ophthalmol},
	year = {2019},
	month = {2019 May 24},
	abstract = {Measuring intraocular pressure (IOP) is the cornerstone of a comprehensive glaucoma exam. In babies or small children, however, IOP measurements are problematic, cannot often be done at the slit lamp, and are sometimes require general anesthesia. Therefore, it is essential for an ophthalmologist who examines a pediatric patient to be aware of the different tonometers used in children, as well as the effects of central corneal thickness (CCT) and anesthesia on IOP measurements. Goldmann applanation tonometry is the gold standard for IOP assessment. Most alternative tonometers tend to give higher IOP readings compared to the Goldmann applanation tonometer, and readings between different tonometers are often not interchangeable. Like Goldmann tonometry, many of these alternative tonometers are affected by CCT, with thicker corneas having artifactually high IOP readings and thinner corneas having artifactually lower IOP readings. Although various machines can be used to compensate for corneal factors (e.g. the dynamic contour tonometer and ocular response analyzer), it is important to be aware that certain ocular diseases can be associated with abnormal CCT values and that their IOP readings need to be interpreted accordingly. Because induction and anesthetics can affect IOP, office IOPs taken in awake patients are always the most accurate.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2019.05.003},
	author = {Fayed, Mahmoud and Chen, Teresa C}
}
@article {1517440,
	title = {The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	pages = {1-10},
	author = {Agrawal R MD FCRS and Betzler B MBBS and Testi I MD and Mahajan S MBBS and Agarwal A MS and Gunasekeran DV MD and Raje D PhD and Aggarwal K MS and Murthy SI DNB and Westcott M FRCSOphth and Chee SP FRCSEd and Mccluskey P MD and Ho SL FRCSGlasg and Teoh S FRCSEd and Cimino L MD and Biswas J MS and Narain S MD and Agarwal M MS and Mahendradas P DNB and Khairallah M MD and Jones N FRCSOphth and Tugal-Tutkun I MD and Babu K DNB and Basu S MS and Carre{\~n}o E MD and Lee R PhD and Al-Dhibi H MD and Bodaghi B MD and Invernizzi A MD and Goldstein DA MD and Herbort CP MD and Barisani-Asenbauer T PhD and Gonz{\'a}lez-L{\'o}pez JJ PhD and Androudi S MD and Bansal R MS and Moharana B MS and Esposti S MD and Tasiopoulou A MD and Nadarajah S MD and Agarwal M DNB and Abraham S MD and Vala R MD and Singh R MS and Sharma A MD and Sharma K PhD and Zierhut M PhD and Kon OM MRCP and Cunningham ET PhD and Kempen JH PhD and Nguyen QD PhD and Pavesio C FRCSOphth and Gupta V MS}
}
@article {1295863,
	title = {Ab Interno Tube Occlusion for Postoperative Hypotony in a Patient With an Ahmed Glaucoma Drainage Device},
	journal = {J Glaucoma},
	volume = {27},
	number = {3},
	year = {2018},
	month = {2018 Mar},
	pages = {e61-e63},
	abstract = {PURPOSE: To report a case of Ahmed glaucoma valve-induced hypotony that was successfully managed with postoperative intraluminal stenting of the aqueous shunt tube.

PATIENT AND METHODS: We describe a 68-year-old man with advanced uveitic glaucoma with an intraocular pressure (IOP) of 25 mm Hg in the left eye. The patient initially responded well to an Ahmed glaucoma valve implant, but at 10 weeks postimplantation, the patient underwent cataract surgery and developed persistent hypotony, choroidal folds, and decreased vision.

RESULTS: Before partial occlusion of the aqueous shunt tube, the patient had an IOP of 3 mm Hg and a best-corrected visual acuity (BCVA) of 20/60. Following intraluminal stenting of the aqueous shunt tube with 4-0 polypropylene suture (Prolene; Ethican), IOP rose from 7 to 10 mm Hg, BCVA improved to 20/30, and the choroidal folds resolved; IOP and BCVA remained stable through 1 year of follow-up and no additional surgical or pharmacological interventions were required.

CONCLUSIONS: Aqueous shunt-induced hypotony can be successfully managed with intraluminal stenting and should be considered before tubal ligation or shunt removal.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000869},
	author = {Feinstein, Max and Moussa, Kareem and Han, Ying}
}
@article {313226,
	title = {Effect of brimonidine on retinal vascular autoregulation and short-term visual function in normal tension glaucoma.},
	journal = {Am J Ophthalmol},
	volume = {158},
	number = {1},
	year = {2014},
	month = {2014 Jul},
	pages = {105-112.e1},
	abstract = {PURPOSE: To assess whether brimonidine 0.15\% alters retinal vascular autoregulation and short-term visual function in normal tension glaucoma patients who demonstrate retinal vascular dysregulation. DESIGN: Nonrandomized clinical trial. METHODS: In this prospective study, 46 normal tension glaucoma patients not previously treated with brimonidine underwent retinal vascular autoregulation testing and visual function assessment using frequency doubling technology perimetry and equivalent noise motion sensitivity testing. We measured blood flow in a major temporal retinal artery with subjects seated and then while reclined for 30 minutes. Patients having a change in retinal blood flow with posture change outside the range previously found in healthy subjects were classified as having retinal vascular dysregulation. They were treated with brimonidine 0.15\% for 8 weeks and designated for retesting. RESULTS: Twenty-three patients demonstrated retinal vascular dysregulation at the initial visit. Younger age (P = .050) and diabetes (P = .055) were marginally significant risk factors for retinal vascular dysregulation. After the 8-week course with brimonidine, 14 of the 17 patients who completed the study showed a return of posture-induced retinal blood flow changes to levels consistent with normal retinal vascular autoregulation (P \&lt; .0001). We found no significant changes in frequency doubling technology perimetry or in motion detection parameters following treatment with brimondine (P \&gt; .09 for all tests performed). CONCLUSIONS: Brimonidine significantly improved impaired retinal vascular autoregulation in normal tension glaucoma patients, but short-term alteration in visual function could not be demonstrated.},
	keywords = {Adrenergic alpha-2 Receptor Agonists, Adult, Aged, Aged, 80 and over, Blood Flow Velocity, Female, Homeostasis, Humans, Intraocular Pressure, Low Tension Glaucoma, Male, Middle Aged, Ophthalmic Solutions, Posture, Prospective Studies, Quinoxalines, Retinal Vessels, Visual Acuity, Visual Field Tests, Visual Fields},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.03.015},
	author = {Feke, Gilbert T and Bex, Peter J and Taylor, Christopher P and Rhee, Douglas J and Turalba, Angela V and Chen, Teresa C and Wand, Martin and Pasquale, Louis R}
}
@article {1363278,
	title = {Effects of dorzolamide-timolol and brimonidine-timolol on retinal vascular autoregulation and ocular perfusion pressure in primary open angle glaucoma},
	journal = {J Ocul Pharmacol Ther},
	volume = {29},
	number = {7},
	year = {2013},
	month = {2013 Sep},
	pages = {639-45},
	abstract = {PURPOSE: To assess whether dorzolamide 2\%-timolol 0.5\% (D/T) and/or brimonidine 0.2\%-timolol 0.5\% (B/T) alters retinal vascular autoregulation (RVA) and seated ocular perfusion pressure (sOPP) in primary open angle glaucoma (POAG) patients who demonstrate retinal vascular dysregulation (RVD) on timolol 0.5\% alone. METHODS: In this prospective, observer-masked, crossover study, 21 POAG patients with untreated intraocular pressure (IOP) \&gt;21 mmHg were treated for 6 weeks with timolol 0.5\%. Subsequently, we measured inferior temporal retinal artery blood flow in the left eye with subjects seated and then while reclined for 30 min using the Canon Laser Blood Flowmeter. Subjects with a change in retinal blood flow in response to posture change outside of the range previously found in healthy subjects were designated as having RVD and randomized to either D/T or B/T for 6 weeks and re-tested. This was followed by treatment with the opposite medication. RESULTS: Seven of the 21 subjects demonstrated RVD in response to posture change following timolol 0.5\%. Multiple linear regression analysis indicated that lower sOPP was the main determinant of RVD (P=0.033). After treatment with D/T, all 7 converted from RVD to normal RVA status (P=0.001). Four of 6 subjects showed a similar return to normal RVA following B/T (P=0.066). Mid-morning sOPP was 41.1{\textpm}5.5 mmHg post-timolol, 46.3{\textpm}6.5 mmHg post-D/T, and 38.6{\textpm}6.0 mmHg post-B/T (D/T vs. B/T, P=0.026). CONCLUSIONS: D/T significantly improved RVA in POAG patients exhibiting RVD while on timolol 0.5\% alone. D/T also increased sOPP compared to B/T. There was no significant difference (P=0.37) between D/T and B/T in improving RVA.},
	keywords = {Adult, Aged, Aged, 80 and over, Antihypertensive Agents, Brimonidine Tartrate, Cross-Over Studies, Drug Combinations, Eye, Female, Glaucoma, Open-Angle, Homeostasis, Humans, Intraocular Pressure, Male, Middle Aged, Prospective Studies, Quinoxalines, Regional Blood Flow, Sulfonamides, Thiophenes, Timolol},
	issn = {1557-7732},
	doi = {10.1089/jop.2012.0271},
	author = {Feke, Gilbert T and Rhee, Douglas J and Turalba, Angela V and Pasquale, Louis R}
}
@article {1647874,
	title = {Outcomes of the Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation Treatment Study: A Randomized Comparative Trial},
	journal = {J Glaucoma},
	volume = {31},
	number = {9},
	year = {2022},
	month = {2022 09 01},
	pages = {701-709},
	abstract = {PRCIS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery. Both treatments were reasonable options for eyes with inadequately controlled IOP after a single GDD. PURPOSE: The purpose of this study is to compare the implantation of a second glaucoma drainage device (SGDD) and transscleral cyclophotocoagulation (CPC) in eyes with inadequately controlled intraocular pressure (IOP), despite the presence of a preexisting glaucoma drainage device. METHODS: Patients with inadequately controlled IOP, despite the medical therapy and a preexisting glaucoma drainage device, were enrolled at 14 clinical centers and randomly assigned to treatment with a SGDD or CPC. MAIN OUTCOME MEASURES: Surgical failure was defined as: (1) IOP <=5\&nbsp;mm\&nbsp;Hg or \&gt;18\&nbsp;mm\&nbsp;Hg or \&lt;20\% reduction below baseline on maximum tolerated topical ocular hypotensive therapy, (2) reoperation for glaucoma, or (3) loss of light perception. The primary outcome measure was overall success with or without adjunctive medical therapy. RESULTS: Forty-two eyes of 42 participants were randomized to SGDD (n=22) or CPC (n=20). Mean duration of follow-up was 18.6 ({\textpm}12.1; range: 1.1-38.6) months. The cumulative success rate was 79\% for SGDD and 88\% for CPC at 1 year ( P =0.63). Although the study was underpowered, no significant differences in IOP, postoperative number of IOP-lowering medications, or adverse events were observed. The number of additional glaucoma surgeries ( P =0.003), office visits during the first 3 months ( P \&lt;0.001), and office visits per month after month 3 ( P \&lt;0.001) were greater in the SGDD group. CONCLUSIONS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery.},
	keywords = {Ciliary Body, Follow-Up Studies, Glaucoma, Glaucoma Drainage Implants, Humans, Intraocular Pressure, Laser Coagulation, Retrospective Studies, Treatment Outcome},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002079},
	author = {Feldman, Robert M and Chuang, Alice Z and Mansberger, Steve L and Tanna, Angelo P and Blieden, Lauren S and Bell, Nicholas P and Gross, Ronald L and Pasquale, Louis R and Greenfield, David S and Liebmann, Jeffrey M and Weinreb, Robert N and ASSISTS Group}
}
@article {1490448,
	title = {Road crossing decisions in real and virtual environments: A comparative study on simulator validity},
	journal = {Accid Anal Prev},
	volume = {137},
	year = {2020},
	month = {2020 Mar},
	pages = {105356},
	abstract = {Virtual reality (VR) is a valuable tool for the assessment of human perception and behavior in a risk-free environment. Investigators should, however, ensure that the used virtual environment is validated in accordance with the experiment{\textquoteright}s intended research question since behavior in virtual environments has been shown to differ to behavior in real environments. This article presents the street crossing decisions of 30 participants who were facing an approaching vehicle and had to decide at what moment it was no longer safe to cross, applying the step-back method. The participants executed the task in a real environment and also within a highly immersive VR setup involving a head-mounted display (HMD). The results indicate significant differences between the two settings regarding the participants{\textquoteright} behaviors. The time-to-contact of approaching vehicles was significantly lower for crossing decisions in the virtual environment than for crossing decisions in the real one. Additionally, it was demonstrated that participants based their crossing decisions in the real environment on the temporal distance of the approaching vehicle (i.e., time-to-contact), whereas the crossing decisions in the virtual environment seemed to depend on the vehicle{\textquoteright}s spatial distance, neglecting the vehicle{\textquoteright}s velocity. Furthermore, a deeper analysis suggests that crossing decisions were not affected by factors such as the participant{\textquoteright}s gender or the order in which they faced the real and the virtual environment.},
	issn = {1879-2057},
	doi = {10.1016/j.aap.2019.105356},
	author = {Feldstein, Ilja T and Dyszak, Georg N}
}
@article {1466917,
	title = {Impending Collision Judgment from an Egocentric Perspective in Real and Virtual Environments: A Review},
	journal = {Perception},
	volume = {48},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {769-795},
	issn = {1468-4233},
	doi = {10.1177/0301006619861892},
	author = {Feldstein, Llja T}
}
@article {1619419,
	title = {Corrigendum to "Road crossing decisions in real and virtual environments: A comparative study on simulator validity" [Accid. Anal. Prevent. 137 (2021) 105356]},
	journal = {Accid Anal Prev},
	volume = {169},
	year = {2022},
	month = {2022 May},
	pages = {106435},
	issn = {1879-2057},
	doi = {10.1016/j.aap.2021.106435},
	author = {Feldstein, Ilja T and Dyszak, Georg N}
}
@article {1504076,
	title = {Pedestrians Accept Shorter Distances to Light Vehicles Than Dark Ones When Crossing the Street},
	journal = {Perception},
	volume = {49},
	number = {5},
	year = {2020},
	month = {2020 May},
	pages = {558-566},
	abstract = {Does the brightness of an approaching vehicle affect a pedestrian{\textquoteright}s crossing decision? Thirty participants indicated their street-crossing intentions when facing approaching light or dark vehicles. The experiment was conducted in a real daylight environment and, additionally, in a corresponding virtual one. A real road with actual cars provides high face validity, while a virtual environment ensures the scenario{\textquoteright}s precise reproducibility and repeatability for each participant. In both settings, participants judged dark vehicles to be a more imminent threat-either closer or moving faster-when compared with light ones. Secondary results showed that participants accepted a significantly shorter time-to-contact when crossing the street in the virtual setting than on the real road.},
	issn = {1468-4233},
	doi = {10.1177/0301006620914789},
	author = {Feldstein, Ilja T and Peli, Eli}
}
@article {1661612,
	title = {The Matricellular Protein SPARC Decreases in the Lacrimal Gland At Adulthood and During Inflammation},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {63},
	number = {13},
	year = {2022},
	month = {2022 Dec 01},
	pages = {8},
	abstract = {PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein abundantly expressed in basement membranes and capsules surrounding a variety of organs and tissues. It mediates extracellular matrix organization and has been implicated in cell contraction. Here, we evaluated the expression of SPARC in the murine lacrimal gland at adulthood and during inflammation. METHODS: Lacrimal glands of young mice (4-6 weeks old) and adult mice (32-40 weeks old) were used for extraction of DNA, RNA, and protein. The presence of SPARC was assessed by quantitative PCR, ELISA, and immunofluorescence microscopy. 5-Methylcytosine and DNA methylation were evaluated using ELISA and bisulfite genomic sequencing, respectively. The effects of cytokines and inflammation in Sparc expression were evaluated in vitro and in the non-obese diabetic (NOD) mouse model of Sj{\"o}gren{\textquoteright}s syndrome. RESULTS: The mRNA and protein levels of SPARC were downregulated in lacrimal glands of mature adult mice presenting age-related histological alterations such as increased deposition of lipofuscin and lipids. Epigenetic analyses indicated that glands in adult mice contain higher levels of global DNA methylation and show increased hypermethylation of specific CpG sites within the Sparc gene promoter. Analysis of smooth muscle actin (SMA)-green fluorescent protein (GFP) transgenic mice revealed that SPARC localizes primarily to myoepithelial cells within the gland. Treatment of myoepithelial cells with IL-1β or TNF-α and the development of inflammation in the NOD mice led to decreased transcription of Sparc. CONCLUSIONS: SPARC is a novel matricellular glycoprotein expressed by myoepithelial cells in the lacrimal gland. Loss of SPARC during adulthood and chronic inflammation might have detrimental consequences on myoepithelial cell contraction and the secretion of tear fluid.},
	keywords = {Age Factors, Animals, Inflammation, Lacrimal Apparatus, Mice, Mice, Inbred NOD, Microscopy, Fluorescence, Osteonectin},
	issn = {1552-5783},
	doi = {10.1167/iovs.63.13.8},
	author = {Feldt, Jessica and Garriz, Angela and Rodriguez Benavente, Maria C and Woodward, Ashley M and Zoukhri, Driss and Arg{\"u}eso, Pablo}
}
@article {1688326,
	title = {Full-length optic nerve regeneration in the absence of genetic manipulations},
	journal = {JCI Insight},
	volume = {8},
	number = {7},
	year = {2023},
	month = {2023 Apr 10},
	abstract = {The inability of mature retinal ganglion cells (RGCs) to regenerate axons after optic nerve injury can be partially reversed by manipulating cell-autonomous and/or -nonautonomous factors. Although manipulations of cell-nonautonomous factors could have higher translational potential than genetic manipulations of RGCs, they have generally produced lower levels of optic nerve regeneration. Here, we report that preconditioning resulting from mild lens injury (conditioning LI, cLI) before optic nerve damage induced far greater regeneration than LI after nerve injury or the pro-inflammatory agent zymosan given either before or after nerve damage. Unlike zymosan-induced regeneration, cLI was unaltered by depleting mature neutrophils or T cells or blocking receptors for known inflammation-derived growth factors (oncomodulin, stromal cell-derived factor 1, CCL5) and was only partly diminished by suppressing CCR2+ monocyte recruitment. Repeated episodes of LI led to full-length optic nerve regeneration, and pharmacological removal of local resident macrophages with the colony stimulating factor 1 receptor inhibitor PLX5622 enabled some axons to reinnervate the brain in just 6 weeks, comparable to the results obtained with the most effective genetic manipulations of RGCs. Thus, cell-nonautonomous interventions can induce high levels of optic nerve regeneration, paving the way to uncovering potent, translatable therapeutic targets for CNS repair.},
	keywords = {Axons, Humans, Nerve Regeneration, Optic Nerve Injuries, Retinal Ganglion Cells, Zymosan},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.164579},
	author = {Feng, Qian and Wong, Kimberly A and Benowitz, Larry I}
}
@article {1664947,
	title = {A Validated Method to Identify Neuro-Ophthalmologists in a Large Administrative Claims Database},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {2},
	year = {2023},
	month = {2023 Jun 01},
	pages = {153-158},
	abstract = {BACKGROUND: Validated methods to identify neuro-ophthalmologists in administrative data do not exist. The development of such method will facilitate research on the quality of neuro-ophthalmic care and health care utilization for patients with neuro-ophthalmic conditions in the United States. METHODS: Using nationally representative, 20\% sample from Medicare carrier files from 2018, we identified all neurologists and ophthalmologists billing at least 1 office-based evaluation and management (E/M) outpatient visit claim in 2018. To isolate neuro-ophthalmologists, the National Provider Identifier numbers of neuro-ophthalmologists in the North American Neuro-Ophthalmology Society (NANOS) directory were collected and linked to Medicare files. The proportion of E/M visits with International Classification of Diseases-10 diagnosis codes that best distinguished neuro-ophthalmic care ("neuro-ophthalmology-specific codes" or NSC) was calculated for each physician. Multiple logistic regression models assessed predictors of neuro-ophthalmology specialty designation after accounting for proportion of ophthalmology, neurology, and NSC claims and primary specialty designation. Sensitivity, specificity, and positive predictive value (PPV) for varying proportions of E/M visits with NSC were calculated. RESULTS: We identified 32,293 neurologists and ophthalmologists who billed at least 1 outpatient E/M visit claim in 2018 in Medicare. Of the 472 NANOS members with a valid individual National Provider Identifier, 399 (84.5\%) had a Medicare outpatient E/M visit in 2018. The model containing only the proportion of E/M visits with NSC best predicted neuro-ophthalmology specialty designation (odds ratio 1.05 [95\% confidence interval 1.04, 1.05]; P \&lt; 0.001; area under the receiver operating characteristic [AUROC] = 0.91). Model predictiveness for neuro-ophthalmology designation was maximized when 6\% of all billed claims were for NSC (AUROC = 0.89; sensitivity: 84.0\%; specificity: 93.9\%), but PPV was low (14.9\%). The threshold was unchanged when limited only to neurologists billing >=1\% ophthalmology claims or ophthalmologists billing >=1\% neurology claims, but PPV increased (33.3\%). CONCLUSIONS: Our study provides a validated method to identify neuro-ophthalmologists who can be further adapted for use in other administrative databases to facilitate future research of neuro-ophthalmic care delivery in the United States.},
	keywords = {Aged, Delivery of Health Care, Humans, Medicare, Neurology, Ophthalmologists, Ophthalmology, United States},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001794},
	author = {Feng, Yilin and Lin, Chun Chieh and Hamedani, Ali G and De Lott, Lindsey B}
}
@article {1806556,
	title = {Cystic-Appearing Eyelid Lesion in a 62-Year-Old Man},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {266-267},
	keywords = {Eyelid Neoplasms, Eyelids, Humans, Male, Middle Aged},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.6637},
	author = {Feng, Yilin and Chiou, Carolina A and Wolkow, Natalie}
}
@article {1661601,
	title = {Intrusion, Extrusion, and Infection of a Hydrolyzed MIRAgel Scleral Buckle},
	journal = {Am J Ophthalmol},
	volume = {247},
	year = {2023},
	month = {2023 Mar},
	pages = {e1-e2},
	keywords = {Humans, Polyhydroxyethyl Methacrylate, Retinal Detachment, Scleral Buckling},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.11.024},
	author = {Feng, Yilin and Chiou, Carolina A and Lee, Nahyoung Grace}
}
@article {1125296,
	title = {A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration},
	journal = {Am J Pathol},
	volume = {187},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {2208-2221},
	abstract = {Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization.},
	keywords = {Aged, Aged, 80 and over, Animals, Antibodies, Neutralizing, Cell Nucleus, Chlamydia, Choroidal Neovascularization, Cytokines, Dipeptides, Gamma Rays, Gene Expression Regulation, Humans, Inflammation, Lipids, Macrophages, Macular Degeneration, Male, Mice, Inbred C57BL, NF-kappa B, Oxidation-Reduction, Protein Transport, Retinal Pigment Epithelium, Toll-Like Receptor 2},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2017.06.015},
	author = {Feng, Lili and Ju, Meihua and Lee, Kei Ying V and Mackey, Ashley and Evangelista, Mariasilvia and Iwata, Daiju and Adamson, Peter and Lashkari, Kameran and Foxton, Richard and Shima, David and Ng, Yin Shan}
}
@article {1632294,
	title = {Implementation of an Online Glaucoma-Specific Quality of Life Computerized Adaptive Test System in a US Glaucoma Hospital},
	journal = {Transl Vis Sci Technol},
	volume = {11},
	number = {2},
	year = {2022},
	month = {2022 Feb 01},
	pages = {24},
	abstract = {Purpose: The feasibility of implementing a computerized adaptive test (CAT) system in routine clinical care in ophthalmology has not been assessed. We evaluated the implementation of a glaucoma-specific CAT (GlauCAT) in outpatients at Massachusetts Eye and Ear Institute. Methods: In this implementation study (July 2020-April 2021), 216 adults (mean {\textpm} SD age 64.8 {\textpm} 15.3 years; 56.0\% women) completed six adaptive GlauCAT quality of life (QOL) tests on an internet-enabled tablet at the clinic. A real-time printable report summarizing domain scores was shared with physicians prior to consultation. The implementation was evaluated using Proctor{\textquoteright}s outcomes: acceptability (patient satisfaction); appropriateness (independent complete rate [\%]); feasibility (acceptance rate [\%]; completion time); and fidelity (percentage of patients discussing GlauCAT results with their physician). Physician barriers/facilitators were explored using open-ended questions. Results: Patients{\textquoteright} mean {\textpm} SD satisfaction score was 3.5 {\textpm} 0.5 of 4, with \&gt;95\% of patients willing to recommend it to others. Of the 216 (89.2\%) patients accepting to participate, 173 (80\%) completed GlauCAT independently. Patients took 8 minutes and 5 seconds (median) to complete all 6 GlauCAT tests. Almost two-thirds (n = 136/216) of the patients reported discussing their GlauCAT results with their doctor. Physicians described the GlauCAT summary report as helpful and user-friendly, although lack of time and uncertainty about how to action information were reported. Conclusions: Pilot implementation of six GlauCAT QOL tests in glaucoma outpatient clinics was feasible and acceptable. Integration of GlauCAT with electronic medical records (EMRs) and evaluation of long-term implementation outcomes are needed. Translational Relevance: GlauCAT{\textquoteright}s multiple outcomes and low test-taking burden makes it attractive for measuring glaucoma-specific QOL in routine clinical care.},
	issn = {2164-2591},
	doi = {10.1167/tvst.11.2.24},
	author = {Fenwick, Eva K and Roldan, Ana M and Halawa, Omar A and Meshkin, Ryan S and Zebardast, Nazlee and Popov, Vesselin and Lis, Przemyslaw and Friedman, David S and Lamoureux, Ecosse L}
}
@article {1593852,
	title = {Antisense Oligonucleotide Therapy for Ophthalmic Conditions},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {5-6},
	year = {2021},
	month = {2021 Aug 18},
	pages = {452-457},
	abstract = {Antisense oligonucleotides (AON) are synthetic single-stranded fragments of nucleic acids that bind to a specific complementary messenger RNA (mRNA) sequence and change the final gene product. AON were initially approved for treating cytomegalovirus retinitis and have shown promise in treating Mendelian systemic disease. AON are currently being investigated as a treatment modality for many ophthalmic diseases, including inherited retinal disorders (IRD), inflammatory response and wound healing after glaucoma surgery, and macular degeneration. They provide a possible solution to gene therapy for IRD that are not candidates for adeno-associated virus (AAV) delivery. This chapter outlines the historical background of AON and reviews clinical applications and ongoing clinical trials.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1914116},
	author = {Ferenchak, Kevin and Deitch, Iris and Huckfeldt, Rachel}
}
@article {1748406,
	title = {Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease},
	journal = {Clin J Am Soc Nephrol},
	year = {2023},
	month = {2023 Aug 03},
	abstract = {The Kidney Precision Medicine Project (KPMP) aims to create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies through molecular investigation of human kidney biopsies obtained from participants with acute kidney injury (AKI) or chronic kidney disease (CKD). We present the case of a 66-year-old woman with diabetic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included diabetes mellitus complicated by neuropathy and eye disease, increased insulin resistance, hypertension, albuminuria, and relatively preserved glomerular filtration rate (early CKD stage 3a). The patient{\textquoteright}s histopathology was consistent with diabetic nephropathy and arterial and arteriolar sclerosis. Three-dimensional, immunofluorescence imaging of the kidney biopsy specimen revealed extensive peri-glomerular neovascularization that was underestimated by standard histopathologic approaches. Spatial transcriptomics was performed to obtain gene expression signatures at discrete areas of the kidney biopsy. Gene expression in the areas of glomerular neovascularization revealed increased expression of genes involved in angiogenic signaling, proliferation and survival of endothelial cells, as well as new vessel maturation and stability. This molecular correlation provides additional insights into the development of kidney disease in patients with diabetes and spotlights how novel molecular techniques employed by the KPMP can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.},
	issn = {1555-905X},
	doi = {10.2215/CJN.0000000000000276},
	author = {Ferkowicz, Michael J and Verma, Ashish and Barwinska, Daria and Ferreira, Ricardo Melo and Henderson, Joel M. and Kirkpatrick, Mary and Silva, Paolo S and Steenkamp, Devin W and Phillips, Carrie L and Waikar, Sushrut S and Sutton, Timothy A and Kidney Precision Medicine Project}
}
@article {1319464,
	title = {C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Jun 26},
	pages = {9679},
	abstract = {The mechanisms that connect complement system activation and basal deposit formation in early stages of age-related macular degeneration (AMD) are insufficiently understood, which complicates the design of efficient therapies to prevent disease progression. Using human fetal (hf) retinal pigment epithelial (RPE) cells, we have established an in vitro model to investigate the effect of complement C3a on RPE cells and its role in the formation of sub-RPE deposits. The results of these studies revealed that C3a produced after C3 activation is sufficient to induce the formation of sub-RPE deposits via complement-driven proteasome inhibition. C3a binds the C3a receptor (C3aR), stimulates deposition of collagens IV and VI underneath the RPE, and impairs the extracellular matrix (ECM) turnover by increased MMP-2 activity, all mediated by downregulation of the ubiquitin proteasome pathway (UPP). The formation of basal deposits can be prevented by the addition of a C3aR antagonist, which restores the UPP activity and ECM turnover. These findings indicate that the cell-based model can be used to test potential therapeutic agents in vitro. The data suggest that modulation of C3aR-mediated events could be a therapeutic approach for treatment of early AMD.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-28143-0},
	author = {Fernandez-Godino, Rosario and Pierce, Eric A}
}
@article {603846,
	title = {Extracellular Matrix Alterations and Deposit Formation in AMD.},
	journal = {Adv Exp Med Biol},
	volume = {854},
	year = {2016},
	month = {2016},
	pages = {53-8},
	abstract = {Age related macular degeneration (AMD) is the primary cause of vision loss in the western world (Friedman et al., Arch Ophthalmol 122:564-572, 2004). The first clinical indication of AMD is the presence of drusen. However, with age and prior to the formation of drusen, extracellular basal deposits accumulate between the retinal pigment epithelium (RPE) and Bruch{\textquoteright}s membrane (BrM). Many studies on the molecular composition of the basal deposits and drusen have demonstrated the presence of extracellular matrix (ECM) proteins, complement components and cellular debris. The evidence reviewed here suggests that alteration in RPE cell function might be the primary cause for the accumulation of ECM and cellular debri found in basal deposits. Further studies are obviously needed in order to unravel the specific pathways that lead to abnormal formation of ECM and complement activation.},
	issn = {0065-2598},
	doi = {10.1007/978-3-319-17121-0_8},
	author = {Fernandez-Godino, Rosario and Pierce, Eric A and Garland, Donita L}
}
@article {1295864,
	title = {Changes in extracellular matrix cause RPE cells to make basal deposits and activate the alternative complement pathway},
	journal = {Hum Mol Genet},
	volume = {27},
	number = {1},
	year = {2018},
	month = {2018 Jan 01},
	pages = {147-159},
	abstract = {The design of efficient therapies for age-related macular degeneration (AMD) is limited by our understanding of the pathogenesis of basal deposits, which form between retinal pigment epithelium (RPE) and Bruch{\textquoteright}s membrane (BrM) early in disease, and involve activation of the complement system. To investigate the roles of BrM, RPE and complement in an AMD, we generated abnormal extracellular matrix (ECM) using CRISPR-edited ARPE-19 cells. We introduced to these cells the p.R345W mutation in EFEMP1, which causes early-onset macular degeneration. The abnormal ECM binds active complement C3 and causes the formation of basal deposits by normal human fetal (hf)RPE cells. Human fetal RPE (hfRPE) cells grown on abnormal ECM or BrM explants from AMD donors show chronic activation of the alternative complement pathway by excessive deposition of C3b. This process is exacerbated by impaired ECM turnover via increased matrix metalloproteinase-2 activity. The local cleavage of C3 via convertase-independent mechanisms can be a new therapeutic target for early AMD.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddx392},
	author = {Fernandez-Godino, Rosario and Bujakowska, Kinga M and Pierce, Eric A}
}
@article {503966,
	title = {A local complement response by RPE causes early-stage macular degeneration.},
	journal = {Hum Mol Genet},
	volume = {24},
	number = {19},
	year = {2015},
	month = {2015 Oct 1},
	pages = {5555-69},
	abstract = {Inherited and age-related macular degenerations (AMDs) are important causes of vision loss. An early hallmark of these disorders is the formation of sub-retinal pigment epithelium (RPE) basal deposits. A role for the complement system in MDs was suggested by genetic association studies, but direct functional connections between alterations in the complement system and the pathogenesis of MD remain to be defined. We used primary RPE cells from a mouse model of inherited MD due to a p.R345W mutation in EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) to investigate the role of the RPE in early MD pathogenesis. Efemp1(R345W) RPE cells recapitulate the basal deposit formation observed in vivo by producing sub-RPE deposits in vitro. The deposits share features with basal deposits, and their formation was mediated by EFEMP1(R345W) or complement component 3a (C3a), but not by complement component 5a (C5a). Increased activation of complement appears to occur in response to an abnormal extracellular matrix (ECM), generated by the mutant EFEMP1(R345W) protein and reduced ECM turnover due to inhibition of matrix metalloproteinase 2 by EFEMP1(R345W) and C3a. Increased production of C3a also stimulated the release of cytokines such as interleukin (IL)-6 and IL-1B, which appear to have a role in deposit formation, albeit downstream of C3a. These studies provide the first direct indication that complement components produced locally by the RPE are involved in the formation of basal deposits. Furthermore, these results suggest that C3a generated by RPE is a potential therapeutic target for the treatment of EFEMP1-associated MD as well as AMD.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddv287},
	author = {Fernandez-Godino, Rosario and Garland, Donita L and Pierce, Eric A}
}
@article {1295865,
	title = {The Challenge of Pediatric Uveitis: Tertiary Referral Center Experience in the United States},
	journal = {Ocul Immunol Inflamm},
	year = {2018},
	month = {2018 Jan 15},
	pages = {1-8},
	abstract = {PURPOSE: To describe the distribution, clinical findings, visual outcomes, treatment, and complications of children with uveitis at a tertiary referral ophthalmic center. METHODS: Retrospective cohort study. We reviewed the medical records of all patients <=16\&nbsp;years with uveitis referred to Massachusetts Eye Research and Surgery Institution from March 2005 to July 2016. RESULTS: Of 286 included children, 62.24\% were female. Mean age of onset was 8.4\&nbsp;years. The uveitis was mainly anterior (61.9\%), recurrent (68.53\%), bilateral (81.82\%), and noninfectious (96.5\%). Idiopathic cases accounted for 51.4\%. The most frequent systemic association was juvenile idiopathic arthritis (34.96\%). The majority of patients (78.32\%) experienced complications. All patients, except one, needed systemic therapy. CONCLUSION: Pediatric uveitis is challenging to diagnose and manage, with frequent and potentially severe complications. Most cases were bilateral, recurrent, and idiopathic. Prompt referral to uveitis-specialized centers and an appropriate systemic therapy are mandatory for good visual outcomes.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2017.1420202},
	author = {Ferrara, Mariantonia and Eggenschwiler, Laura and Stephenson, Andrew and Montieth, Alyssa and Nakhoul, Nakhoul and Ara{\`u}jo-Miranda, Rafael and Foster, C Stephen}
}
@article {1363279,
	title = {Nerves and neovessels inhibit each other in the cornea},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {1},
	year = {2013},
	month = {2013 Jan 28},
	pages = {813-20},
	abstract = {PURPOSE: To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS: b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epithelium-derived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS: No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5\% reduction, P = 0.001) and PEDF protein expression (64\% reduction, P \&lt; 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION: Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis.},
	keywords = {Animals, Cornea, Corneal Neovascularization, Denervation, Disease Models, Animal, Electrolysis, Enzyme-Linked Immunosorbent Assay, Eye Proteins, Fluorescent Antibody Technique, Indirect, Leukocyte Common Antigens, Male, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Nerve Degeneration, Nerve Growth Factors, Ophthalmic Artery, Platelet Endothelial Cell Adhesion Molecule-1, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Serpins, Signal Transduction, Trigeminal Nerve, Tubulin, Vascular Endothelial Growth Factor Receptor-3},
	issn = {1552-5783},
	doi = {10.1167/iovs.11-8379},
	author = {Ferrari, Giulio and Hajrasouliha, Amir R and Sadrai, Zahra and Ueno, Hiroki and Chauhan, Sunil K and Dana, Reza}
}
@article {1179181,
	title = {Blindness and social trust: The effect of early visual deprivation on judgments of trustworthiness},
	journal = {Conscious Cogn},
	volume = {55},
	year = {2017},
	month = {2017 Oct},
	pages = {156-164},
	abstract = {Investigating the impact of early visual deprivation on evaluations related to social trust has received little attention to date. This is despite consistent evidence suggesting that early onset blindness may interfere with the normal development of social skills. In this study, we investigated whether early blindness affects judgments of trustworthiness regarding the actions of an agent, with trustworthiness representing the fundamental dimension in the social evaluation. Specifically, we compared performance between a group of early blind individuals with that of sighted controls in their evaluation of trustworthiness of an agent after hearing a pair of two positive or two negative social behaviors (impression formation). Participants then repeated the same evaluation following the presentation of a third (consistent or inconsistent) behavior regarding the same agent (impression updating). Overall, blind individuals tended to give similar evaluations compared to their sighted counterparts. However, they also valued positive behaviors significantly more than sighted controls when forming their impression of an agent{\textquoteright}s trustworthiness. Moreover, when inconsistent information was provided, blind individuals were more prone to revise their initial evaluation compared to controls. These results suggest that early visual deprivation may have a dramatic effect on the evaluation of social factors such as trustworthiness.},
	issn = {1090-2376},
	doi = {10.1016/j.concog.2017.08.005},
	author = {Ferrari, C. and Vecchi, T and Merabet, L B and Cattaneo, Z}
}
@article {1748351,
	title = {An affordable and semiautomated approach as a novel strategy for the extraction of DNA using magnetic ionic liquids followed by real time-polymerase chain reaction},
	journal = {Anal Methods},
	volume = {15},
	number = {30},
	year = {2023},
	month = {2023 Aug 03},
	pages = {3752-3757},
	abstract = {This technical note describes a novel and straightforward experimental strategy for the extraction/capture of DNA using magnetic ionic liquid (MIL) followed by real time-polymerase chain reaction (qPCR) analysis. An affordable and low-cost magneto-based multiwell platform was first examined for capturing DNA allowing for simultaneous extractions that increased the analysis throughput of the experimental workflow. This configuration was composed of a series of neodymium rod magnets attached to a multiwell device in which a magneto-active extraction phase (MIL) was suspended for a single drop microextraction (SDME) approach. In this configuration, up to 32 extractions were able to be performed simultaneously, and DNA was successfully extracted from aqueous samples. Furthermore, as a proof-of-concept, this affordable and simple experimental strategy proved to be efficient for the extraction/capture of DNA from challenging samples such as whole blood without any pretreatment. This fact also consists of important feature compared to previous methodologies that required additional steps of sample preparation.},
	keywords = {DNA, Ionic Liquids, Magnetic Phenomena, Magnets, Real-Time Polymerase Chain Reaction},
	issn = {1759-9679},
	doi = {10.1039/d3ay00751k},
	author = {Ferreira Neto, Luiz Carlos and Alves, M{\^o}nica Silva and Prichula, Janira and Agnes, Grasiela and de Oliveira, Tiago Franco and Trentin, Danielle and Merib, Josias}
}
@article {560271,
	title = {IgG4-related Orbital Disease and Its Mimics in a Western Population.},
	journal = {Am J Surg Pathol},
	year = {2015},
	month = {2015 Sep 16},
	abstract = {Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue). Fifteen patients had IgG4-related dacryoadenitis or orbital inflammation. These patients included 9 men and 6 women, aged 24 to 77 years (median, 64 y). Lesions involved orbital soft tissue (8 cases), lacrimal gland (6 cases), and canthus (1 case). In 1 case, focal in situ follicular neoplasia was seen in a background of IgG4-RD. In another case, a clonal IGH gene rearrangement was detected. Four patients with IgG4-RD had evidence of IgG4-RD in other anatomic sites. Five patients, 1 man and 4 women, aged 26 to 74 years (median 50 y) had orbital lesions (2 involving lacrimal gland, 3 involving soft tissue) suspicious for, but not diagnostic of, IgG4-RD. Of 16 patients with IgG4-RD or probable IgG4-RD with information available regarding the course of their disease, 11 patients experienced recurrent or persistent orbital disease. However, no patient developed lymphoma, and no patient died of complications of IgG4-RD. Eighteen patients had lesions not representing IgG4-RD. They included 6 male and 12 female individuals aged 6 to 77 years (median, 47 y). These patients had a variety of diseases, including granulomatosis with polyangiitis (3 cases), Rosai-Dorfman disease (1 case), nonspecific chronic inflammation and fibrosis involving lacrimal gland or soft tissue (12 cases), and others. Clinical and pathologic findings among our patients with IgG4-RD involving the orbit are similar to those previously described in Asian patients. Careful evaluation of histologic and immunophenotypic features and clinical correlation are required to distinguish orbital IgG4-RD from other sclerosing inflammatory lesions in the orbit.},
	issn = {1532-0979},
	doi = {10.1097/PAS.0000000000000497},
	author = {Ferry, Judith A and Klepeis, Veronica and Sohani, Aliyah R and Harris, Nancy Lee and Preffer, Frederic I and Stone, John H and Grove, Arthur and Deshpande, Vikram}
}
@article {1559549,
	title = {Association of Cognitive Function and Retinal Neural and Vascular Structure in Type 1 Diabetes},
	journal = {J Clin Endocrinol Metab},
	volume = {106},
	number = {4},
	year = {2021},
	month = {2021 Mar 25},
	pages = {1139-1149},
	abstract = {CONTEXT: Cognitive dysfunction is a growing and understudied public health issue in the aging type 1 diabetic population and is difficult and time-consuming to diagnose. Studies in long duration type 1 diabetes have reported the presence of proliferative diabetic retinopathy was associated with cognitive dysfunction. OBJECTIVE: This study assessed whether structural and vascular abnormalities of the retina, representing an extension of the central nervous system, are associated with cognitive impairment and other complications of type 1 diabetes. METHODS: An observational cross-sectional study of individuals with 50 or more years of type 1 diabetes (Joslin Medalist Study) was conducted at a university hospital in the United States. The study included 129 participants with complete cognitive testing. Validated cognitive testing measures included psychomotor speed, and immediate, and delayed memory. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed to obtain neural retinal layer thicknesses and vascular density for superficial (SCP) and deep retinal capillary plexus (DCP). Multivariable modeling was adjusted for potential confounders associated with outcomes in unadjusted analyses. RESULTS: Decreased vessel density of the SCP and DCP was associated with worse delayed memory (DCP: P = .002) and dominant hand psychomotor speed (SCP: P = .01). Thinning of the retinal outer nuclear layer was associated with worse psychomotor speed both in nondominant and dominant hands (P = .01 and P = .05, respectively). Outer plexiform layer thickness was associated with delayed memory (P = .04). CONCLUSION: These findings suggest that noninvasive retinal imaging using OCT and OCTA may assist in estimating the risks for cognitive dysfunction in people with type 1 diabetes.},
	issn = {1945-7197},
	doi = {10.1210/clinem/dgaa921},
	author = {Fickweiler, Ward and Wolfson, Emily A and Paniagua, Samantha M and Yu, Marc Gregory and Adam, Atif and Bahnam, Vanessa and Sampani, Konstantina and Wu, I-Hsien and Musen, Gail and Aiello, Lloyd P and Shah, Hetal and Sun, Jennifer K and King, George L}
}
@article {1664977,
	title = {Circulatory Biomarkers and Diabetic Retinopathy in Racial and Ethnic Populations},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {5},
	year = {2023},
	month = {2023 Jul},
	pages = {446-456},
	abstract = {Clinical staging systems for diagnosis and treatment of diabetic retinopathy (DR) must closely relate to endpoints that are both relevant for patients and feasible for physicians to implement. Current DR staging systems for clinical eye care and research provide detailed phenotypic characterization to predict patient outcomes in diabetes but have limitations. Biochemical biomarkers provide a rich pool of potential candidates for new DR staging systems that can be readily measured in accessible fluids. Circulating biomarkers that are specific to the retina and relate to angiogenesis and inflammation have been suggested as relevant for DR. Although there is a lack of multi-ethnic studies evaluating circulatory biomarkers in DR, variability in circulatory biomarkers have been reported in people from different ethnic and racial backgrounds. Therefore, there is a need for future studies to evaluate individual or combinations of biomarkers in diverse populations with DR from different ethnic and racial backgrounds.},
	keywords = {Biomarkers, Diabetes Mellitus, Diabetic Retinopathy, Ethnic and Racial Minorities, Humans, Retina, Social Determinants of Health},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2168488},
	author = {Fickweiler, Ward and Mitzner, Margalit and Jacoba, Cris Martin P and Sun, Jennifer K}
}
@article {1593861,
	title = {Response to Letter to the Editor from [Ludmila Brunerova]: (Association of Cognitive Function and Retinal Neural and Vascular Structure in Type 1 Diabetes)},
	journal = {J Clin Endocrinol Metab},
	year = {2021},
	month = {2021 May 26},
	issn = {1945-7197},
	doi = {10.1210/clinem/dgab351},
	author = {Fickweiler, Ward and Wolfson, Emily A and Paniagua, Samantha M and Yu, Marc Gregory and Adam, Atif and Bahnam, Vanessa and Sampani, Konstantina and Wu, I-Hsien and Musen, Gail and Aiello, Lloyd P and Shah, Hetal and Sun, Jennifer K and King, George L}
}
@article {1647888,
	title = {Elevated Retinol Binding Protein 3 Concentrations Are Associated With Decreased Vitreous Inflammatory Cytokines, VEGF, and Progression of Diabetic Retinopathy},
	journal = {Diabetes Care},
	volume = {45},
	number = {9},
	year = {2022},
	month = {2022 Sep 01},
	pages = {2159-2162},
	abstract = {OBJECTIVE: To correlate inflammatory cytokines and vascular endothelial growth factor (VEGF) in vitreous and plasma with vitreous retinol binding protein 3 (RBP3), diabetic retinopathy (DR) severity, and DR worsening in a population with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: RBP3, VEGF, and inflammatory cytokines were measured in plasma and vitreous samples (n = 205) from subjects of the Joslin Medalist Study and Beetham Eye Institute. RESULTS: Higher vitreous RBP3 concentrations were associated with less severe DR (P \&lt; 0.0001) and a reduced risk of developing proliferative DR (PDR) (P \&lt; 0.0001). Higher RBP3 correlated with increased photoreceptor segment thickness and lower vitreous interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and TNF-β (P \&lt; 0.05). PDR was associated with lower vitreous interferon-γ and IL-10 and higher VEGF, IL-6, and IL-15 (P \&lt; 0.05), but was not associated with their plasma concentrations. CONCLUSIONS: Higher vitreous RBP3 concentrations are associated with less severe DR and slower rates of progression to PDR, supporting its potential as a biomarker and therapeutic agent for preventing DR worsening, possibly by lowering retinal VEGF and inflammatory cytokines.},
	keywords = {Cytokines, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Enzyme-Linked Immunosorbent Assay, Eye Proteins, Humans, Retinol-Binding Proteins, Vascular Endothelial Growth Factor A, Vitreous Body},
	issn = {1935-5548},
	doi = {10.2337/dc22-0165},
	author = {Fickweiler, Ward and Park, Hyunseok and Park, Kyoungmin and Mitzner, Margalit G and Chokshi, Tanvi and Boumenna, Tahani and Gautier, John and Zaitsu, Yumi and Wu, I-Hsien and Cavallerano, Jerry and Aiello, Lloyd P and Sun, Jennifer K and King, George L}
}
@article {647366,
	title = {Facilitating Glaucoma Diagnosis With Intereye Retinal Nerve Fiber Layer Asymmetry Using Spectral-Domain Optical Coherence Tomography.},
	journal = {J Glaucoma},
	volume = {25},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {167-76},
	abstract = {PURPOSE: To test whether increased intereye retinal nerve fiber layer (RNFL) asymmetry may be indicative of glaucoma. To determine the best statistical methods and intereye RNFL cutoffs for differentiating between normal and glaucoma subjects to better alert clinicians to early glaucomatous damage. METHODS: Sixty-six primary open-angle glaucoma (OAG) and 40 age-matched normal subjects had both eyes imaged at the Massachusetts Eye and Ear Infirmary with a commercially available spectral-domain optical coherence tomography (OCT) machine. Statistical methodologies were used to find cutoffs that achieved the best sensitivities and specificities for differentiating OAG from normal subjects. RESULTS: Intereye RNFL asymmetry for global average, all quadrants, and all sectors was significantly greater in OAG than normal subjects. Intereye RNFL asymmetry for global average showed the greatest statistical difference (P\&lt;0.001) between OAG (23.64{\textpm}14.90 μm) and normal eyes (3.58{\textpm}3.96 μm), with 6.60 times greater asymmetry in OAG eyes. The inferior quadrant showed the second greatest difference, with 3.91 times greater asymmetry in OAG eyes. Using a statistically determined cutoff of 6.0 μm as abnormal, intereye RNFL asymmetry for global average achieved a sensitivity of 74.24\% and specificity of 90\% in differentiating between normal and OAG subjects, achieving a better combination of sensitivity and specificity than intereye RNFL asymmetry of any quadrant or sector. CONCLUSIONS: Intereye RNFL asymmetry may be a useful clinical OCT measurement to provide quantitative assessment of early glaucomatous damage. Newly developed algorithms for intereye RNFL asymmetry may improve the ability to detect glaucoma.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000080},
	author = {Field, Matthew G and Alasil, Tarek and Baniasadi, Neda and Que, Christian and Simavli, Huseyin and Sobeih, Doaa and Sola-Del Valle, David and Best, Matthew J and Chen, Teresa C}
}
@article {416841,
	title = {Vision research special issue: Sight restoration: Prosthetics, optogenetics and gene therapy.},
	journal = {Vision Res},
	volume = {111},
	number = {Pt B},
	year = {2015},
	month = {2015 Jun},
	pages = {115-23},
	issn = {1878-5646},
	doi = {10.1016/j.visres.2015.04.012},
	author = {Fine, Ione and Cepko, Connie L and Landy, Michael S}
}
@article {1452959,
	title = {Mechanisms and consequences of gut commensal translocation in chronic diseases},
	journal = {Gut Microbes},
	year = {2019},
	month = {2019 Jul 15},
	pages = {1-14},
	abstract = {Humans and other mammalian hosts have evolved mechanisms to control the bacteria colonizing their mucosal barriers to prevent invasion. While the breach of barriers by bacteria typically leads to overt infection, increasing evidence supports a role for translocation of commensal bacteria across an impaired gut barrier to extraintestinal sites in the pathogenesis of autoimmune and other chronic, non-infectious diseases. Whether gut commensal translocation is a cause or consequence of the disease is incompletely defined. Here we discuss factors that lead to translocation of live bacteria across the gut barrier. We expand upon our recently published demonstration that translocation of the gut pathobiont can induce autoimmunity in susceptible hosts and postulate on the role of species as instigators of chronic, non-infectious diseases.},
	issn = {1949-0984},
	doi = {10.1080/19490976.2019.1629236},
	author = {Fine, Rebecca L and Manfredo Vieira, Silvio and Gilmore, Michael S and Kriegel, Martin A}
}
@article {1782316,
	title = {Tear and Saliva Metabolomics in Evaporative Dry Eye Disease in Females},
	journal = {Metabolites},
	volume = {13},
	number = {11},
	year = {2023},
	month = {2023 Nov 02},
	abstract = {Accurate diagnosis of dry eye disease (DED) is challenging, and even today there is no gold standard biomarker of DED. Hypothesis-free global metabolomic studies of tears from DED patients have great potential to discover metabolites and pathways affected in the pathophysiology of DED, and to identify possible future biomarkers. These metabolites and biomarkers could be important for diagnosing and monitoring disease as well as for new therapeutic targets and strategies. As DED is associated with dry mouth, this study aimed to perform metabolomic analyses of tears and saliva from patients with decreased tear film break-up time but normal Schirmer test, and age-matched controls with both tear production and stability within physiological range. We applied strict inclusion criteria to reduce sampling bias in the metabolomic analyses and selected only age-matched females with Schirmer test values between 10-15 mm/5 min. The tear film analysis arm included 19 patients (with tear film break-up time 0-5 s) and 12 controls (with tear film break-up time 10-30 s), while the salivary analysis arm consisted of a subset which included 18 patients and six controls. Metabolomic analyses were performed using liquid chromatography and high-resolution mass spectrometry. Analyses using a global database search detected a total of 56 metabolites in tear samples that were significantly different between the groups. Of these, several have known associations with DED. These metabolites are present in meibum and have anti-oxidative characteristics or associations with the ocular microbiome, and altered concentrations suggest that they may play a significant role in DED associated with decreased tear film stability. In saliva, hypotaurine levels were lower among patients with tear film instability. In this pilot study, we found different levels of several metabolites in patients with decreased tear film break-up time that may have associations with DED. Future studies are required to replicate our findings and clarify the exact roles of these metabolites.},
	issn = {2218-1989},
	doi = {10.3390/metabo13111125},
	author = {Fineide, Fredrik A and Tashbayev, Behzod and Elgst{\o}en, Katja B P and Sand{\r a}s, Elise M and Rootwelt, Helge and Hynne, H{\r a}vard and Chen, Xiangjun and R{\ae}der, Sten and Vehof, Jelle and Dartt, Darlene and Jensen, Janicke L and Utheim, Tor P}
}
@article {1466914,
	title = {Membrane-associated mucins of the ocular surface: New genes, new protein functions and new biological roles in human and mouse},
	journal = {Prog Retin Eye Res},
	year = {2019},
	month = {2019 Sep 04},
	pages = {100777},
	abstract = {The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2019.100777},
	author = {Fini, M Elizabeth and Jeong, Shinwu and Gong, Haiyan and Martinez-Carrasco, Rafael and Laver, Nora M V and Hijikata, Minako and Keicho, Naoto and Arg{\"u}eso, Pablo}
}
@article {1732666,
	title = {Environmental Impact of a Pediatric and Young Adult Virtual Medicine Program: A Lesson from the COVID-19 Pandemic},
	journal = {Acad Pediatr},
	year = {2023},
	month = {2023 Jul 25},
	abstract = {OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic led to the expansion of virtual medicine as a method to provide patient care. We aimed to determine the impact of pediatric and young adult virtual medicine use on fossil fuel consumption, greenhouse gas and non-greenhouse traffic-related air pollutant emissions. METHODS: We conducted a retrospective analysis of all virtual medicine patients at a single quaternary-care children{\textquoteright}s hospital with a geocoded address in the Commonwealth of Massachusetts prior to (3/16/2019-3/15/2020) and during the COVID-19 pandemic (3/16/2020-3/15/2021). Primary outcomes included patient travel distance, gasoline consumption, carbon dioxide and fine particulate matter emissions as well as savings in main hospital energy use. RESULTS: There were 3,846 and 307,273 virtual visits performed with valid Massachusetts geocoded addresses prior to and during the COVID-19 pandemic, respectively. During one year of the pandemic, virtual medicine services resulted in a total reduction of 620,231 gallons of fossil fuel use and $1,620,002 avoided expenditure as well as 5,492.9 metric tons of carbon dioxide and 186.3 kilograms of fine particulate matter emitted. There were 3.1 million fewer kilowatt hours used by the hospital intra-pandemic compared to the year prior. Accounting for equipment emissions, the combined intra-pandemic emission reductions are equivalent to the electricity required by 1,234 homes for one year. CONCLUSIONS: Widespread pediatric institutional use of virtual medicine provided environmental benefits. The true potential of virtual medicine for decreasing the environmental footprint of healthcare lies in scaling this mode of care to patient groups across the state and nation when medically feasible.},
	issn = {1876-2867},
	doi = {10.1016/j.acap.2023.07.011},
	author = {Finkelstein, Julia B and Hauptman, Marissa and Acosta, Keith and Flanagan, Shelby and Cahill, Dylan and Smith, Brian and Bernstein, Aaron and Shah, Shalini H and Kaur, Ravneet and Meyers, Heather and Shah, Ankoor S and Meara, John G and Estrada, Carlos R}
}
@article {1626094,
	title = {Pediatric Clinicians{\textquoteright} Use of Telemedicine: Qualitative Interview Study},
	journal = {JMIR Hum Factors},
	volume = {8},
	number = {4},
	year = {2021},
	month = {2021 Dec 02},
	pages = {e29941},
	abstract = {BACKGROUND: Bedside manner describes how clinicians relate to patients in person. Telemedicine allows clinicians to connect virtually with patients using digital tools. Effective virtual communication or webside manner may require modifications to traditional bedside manner. OBJECTIVE: This study aims to understand the experiences of telemedicine providers with patient-to-provider virtual visits and communication with families at a single large-volume children{\textquoteright}s hospital to inform program development and training for future clinicians. METHODS: A total of 2 focus groups of pediatric clinicians (N=11) performing virtual visits before the COVID-19 pandemic, with a range of experiences and specialties, were engaged to discuss experiential, implementation, and practice-related issues. Focus groups were facilitated using a semistructured guide covering general experience, preparedness, rapport strategies, and suggestions. Sessions were digitally recorded, and the corresponding transcripts were reviewed for data analysis. The transcripts were coded based on the identified main themes and subthemes. On the basis of a higher-level analysis of these codes, the study authors generated a final set of key themes to describe the collected data. RESULTS: Theme consistency was identified across diverse participants, although individual clinician experiences were influenced by their specialties and practices. A total of 3 key themes emerged regarding the development of best practices, barriers to scalability, and establishing patient rapport. Issues and concerns related to privacy were salient across all themes. Clinicians felt that telemedicine required new skills for patient interaction, and not all were comfortable with their training. CONCLUSIONS: Telemedicine provides benefits as well as challenges to health care delivery. In interprofessional focus groups, pediatric clinicians emphasized the importance of considering safety and privacy to promote rapport and webside manner when conducting virtual visits. The inclusion of webside manner instructions within training curricula is crucial as telemedicine becomes an established modality for providing health care.},
	issn = {2292-9495},
	doi = {10.2196/29941},
	author = {Finkelstein, Julia B and Tremblay, Elise S and Van Cain, Melissa and Farber-Chen, Aaron and Schumann, Caitlin and Brown, Christina and Shah, Ankoor S and Rhodes, Erinn T}
}
@article {913441,
	title = {Assessing Resident Cataract Surgery Outcomes Using Medicare Physician Quality Reporting System Measures.},
	journal = {J Surg Educ},
	volume = {73},
	number = {5},
	year = {2016},
	month = {2016 Sep-Oct},
	pages = {774-9},
	abstract = {OBJECTIVES: To assess resident cataract surgery outcomes at an academic teaching institution using 2 Physician Quality Reporting System (PQRS) cataract measures, which are intended to serve as a proxy for quality of surgical care. DESIGN: A retrospective review comparing cataract surgery outcomes of resident and attending surgeries using 2 PQRS measures: (1) 20/40 or better best-corrected visual acuity following cataract surgery and (2) complications within 30 days following cataract surgery requiring additional surgical procedures. SETTING: An academic ophthalmology center. PARTICIPANTS: A total of 2487 surgeries performed at the Massachusetts Eye and Ear Infirmary from January 1, 2011 to December 31, 2012 were included in this study. RESULTS: Of all 2487 cataract surgeries, 98.95\% achieved a vision of at least 20/40 at or before 90 days, and only 0.64\% required a return to the operating room for postoperative complications. Of resident surgeries, 98.9\% (1370 of 1385) achieved 20/40 vision at or before 90 days follow-up. Of attending surgeries, 99.0\% (1091 of 1102) achieved 20/40 vision at or before 90 days (p = 1.00). There were no statistically significant differences between resident and attending cases regarding postoperative complications needing a return to the operating room (i.e., 0.65\%, or 9 of 1385 resident cases vs 0.64\%, or 7 of 1102 attending cases; p = 1.00). CONCLUSIONS: Using PQRS Medicare cataract surgery criteria, this study establishes new benchmarks for cataract surgery outcomes at a teaching institution and supplemental measure for assessing resident surgical performance. Excellent cataract outcomes were achieved at an academic teaching institution, with results exceeding Medicare thresholds of 50\%. There appears to be no significant difference in supervised trainee and attending cataract surgeon outcomes using 2 PQRS measures currently used by Medicare to determine physician reimbursement and quality of care.},
	issn = {1878-7452},
	doi = {10.1016/j.jsurg.2016.04.007},
	author = {Finn, Avni P and Borboli-Gerogiannis, Sheila and Brauner, Stacey and Peggy Chang, Han-Ying and Chen, Sherleen and Gardiner, Matthew and Greenstein, Scott H and Kloek, Carolyn and Miller, Joan W and Chen, Teresa C}
}
@article {1782361,
	title = {Test-retest repeatability and agreement of the quantitative contrast sensitivity function test: towards the validation of a new clinical endpoint},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	year = {2023},
	month = {2023 Nov 13},
	abstract = {PURPOSE: The purpose of this study is to investigate test-retest reliability and agreement of the quantitative contrast sensitivity function test (qCSF) in the retina clinic. METHODS: A total of 121 right eyes of 121 patients were tested and consecutively re-tested with qCSF in the retina clinic. Outcomes included area under the logarithm of contrast sensitivity function curve (AULCSF), contrast acuity, and contrast sensitivity thresholds at 1-18 cycles per degree (cpd). Test-retest means were compared with paired t-test, variability was compared with the Brown-Forsythe test, and intraclass correlation coefficient (ICC) and Bland Altman plots evaluated reliability and agreement. RESULTS: Mean test-retest differences for all qCSF metrics ranged from 0.02 to 0.05 log units without statistically significant differences in variability. Standard deviations ranged from 0.08 to 0.14. Coefficients of repeatability ranged from 0.16 to 0.27 log units. ICC \&gt; 0.9 for all metrics except 1cpd (ICC = 0.84, all p \&lt; 0.001); AULCSF ICC = 0.971. CONCLUSION: qCSF-measured contrast sensitivity shows great test-retest repeatability and agreement in the retina clinic.},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06291-y},
	author = {Finn, Matthew and Vingopoulos, Filippos and Zhao, Yan and Zhou, Paul and Bannerman, Augustine and Romano, Francesco and Ding, Xinyi and Hassan, Zakariyya and Patel, Nimesh A and Wu, David M and Miller, John B}
}
@article {913446,
	title = {A Retrospective Review of Orbital Decompression for Thyroid Orbitopathy with Endoscopic Preservation of the Inferomedial Orbital Bone Strut},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {5},
	year = {2017},
	month = {2017 Sep/Oct},
	pages = {334-339},
	abstract = {PURPOSE: To determine incidence of new-onset diplopia, resolution of preexisting diplopia, and impact on proptosis resulting from endoscopic orbital decompression with and without preservation of the inferomedial orbital strut for thyroid orbitopathy. METHODS: Retrospective review of all patients undergoing endoscopic 2- or 3-wall decompression with or without preservation of the strut for thyroid orbitopathy from January 2012 to June 2015. RESULTS: Twenty-six patients (45 orbits) were included and divided into 4 primary categories: 2-wall decompression with strut preservation (4 orbits, 8\%), 2-wall decompression with strut removal (7 orbits, 16\%), 3-wall decompression with strut preservation (27 orbits, 60\%), and 3-wall decompression with strut removal (7 orbits, 16\%). The incidence of new-onset diplopia was 20\% (2/10 patients without preoperative diplopia) overall and 16\% in the strut preservation group (1/6 patients without preoperative diplopia). Resolution of diplopia occurred in 4 of 16 patients (25\%) with preoperative diplopia, and all 4 had been treated with a 3-wall decompression with strut preservation. Resolution of diplopia in the group treated with strut preservation was 36\% (4/11 patients with preoperative diplopia), and 0\% of the 5 diplopic patients treated without strut preservation. Reduction in proptosis was statistically greater in those treated with strut removal (p = 0.003). CONCLUSIONS: This study demonstrates that endoscopic orbital decompression with preservation of the inferomedial bone strut results in a comparable to lower rate of new-onset diplopia compared with other reported techniques. When combined with 3-wall balanced decompression, this technique demonstrates a high rate of resolution of preexisting diplopia.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000782},
	author = {Finn, Avni P and Bleier, Benjamin and Cestari, Dean M and Kazlas, Melanie A and Dagi, Linda R and Lefebvre, Daniel R and Yoon, Michael K and Freitag, Suzanne K}
}
@article {1452964,
	title = {Pathogenicity of Enterococci},
	journal = {Microbiol Spectr},
	volume = {7},
	number = {4},
	year = {2019},
	month = {2019 Jul},
	abstract = {Enterococci are unusually well adapted for survival and persistence in a variety of adverse environments, including on inanimate surfaces in the hospital environment and at sites of infection. This intrinsic ruggedness undoubtedly played a role in providing opportunities for enterococci to interact with other overtly drug-resistant microbes and acquire additional resistances on mobile elements. The rapid rise of antimicrobial resistance among hospital-adapted enterococci has rendered hospital-acquired infections a leading therapeutic challenge. With about a quarter of a genome of additional DNA conveyed by mobile elements, there are undoubtedly many more properties that have been acquired that help enterococci persist and spread in the hospital setting and cause diseases that have yet to be defined. Much remains to be learned about these ancient and rugged microbes, particularly in the area of pathogenic mechanisms involved with human diseases.},
	issn = {2165-0497},
	doi = {10.1128/microbiolspec.GPP3-0053-2018},
	author = {Fiore, Elizabeth and Van Tyne, Daria and Gilmore, Michael S}
}
@article {1667716,
	title = {Real-Time Analysis of Bioenergetics in Primary Human Retinal Pigment Epithelial Cells Using High-Resolution Respirometry},
	journal = {J Vis Exp},
	number = {192},
	year = {2023},
	month = {2023 Feb 03},
	abstract = {Metabolic dysfunction of retinal pigment epithelial cells (RPE) is a key pathogenic driver of retinal diseases such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Since RPE are highly metabolically-active cells, alterations in their metabolic status reflect changes in their health and function. High-resolution respirometry allows for real-time kinetic analysis of the two major bioenergetic pathways, glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), through quantification of the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), respectively. The following is an optimized protocol for conducting high-resolution respirometry on primary human retinal pigment epithelial cells (H-RPE). This protocol provides a detailed description of the steps involved in producing bioenergetic profiles of RPE to define their basal and maximal OXPHOS and glycolytic capacities. Exposing H-RPE to different drug injections targeting the mitochondrial and glycolytic machinery results in defined bioenergetic profiles, from which key metabolic parameters can be calculated. This protocol highlights the enhanced response of BAM15 as an uncoupling agent compared to carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) to induce the maximal respiration capacity in RPE. This protocol can be utilized to study the bioenergetic status of RPE under different disease conditions and test the efficacy of novel drugs in restoring the basal metabolic status of RPE.},
	keywords = {Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Energy Metabolism, Epithelial Cells, Glycolysis, Humans, Kinetics, Retinal Pigment Epithelium, Retinal Pigments},
	issn = {1940-087X},
	doi = {10.3791/64572},
	author = {Fitch, Tessa C and Frank, Scott I and Li, Yutong Kelly and Saint-Geniez, Magali and Kim, Leo A and Shu, Daisy Y}
}
@article {1619423,
	title = {The association between visual display terminal use and dry eye: a review},
	journal = {Acta Ophthalmol},
	volume = {100},
	number = {4},
	year = {2022},
	month = {2022 Jun},
	pages = {357-375},
	abstract = {BACKGROUND: Dry eye disease (DED) is a multifactorial disease of the tear film and ocular surface. It causes ocular symptoms, reduced quality of life and a considerable economic burden on society. Prolonged use of visual display terminals (VDTs) has been suggested as an important risk factor for DED. PURPOSE: This review aims to study the association between DED and VDT use with an emphasis on the prevalence of DED among VDT users and harmful daily duration of VDT use. METHODS: A PubMed search was conducted and yielded 57 relevant articles based on a set of inclusion and exclusion criteria. The studies were subclassified according to study design. RESULTS: The far majority of the studies showed an association between VDT use and DED or DED-related signs and symptoms. The prevalence of definite or probable DED in VDT and office workers ranged from 26\% to 70\%, with as few as 1-2 hr of VDT exposure per day being associated with DED. CONCLUSION: VDT use is strongly associated with DED. VDT-associated DED is prevalent, but the exact prevalence needs to be further elucidated using standardized DED diagnosis criteria. Furthermore, a safe lower limit of daily VDT use has yet to be established. More research is needed on the effect of digitalization and digital transformation, which are particularly high during the time of the COVID-19 pandemic.},
	keywords = {Computer Terminals, COVID-19, Cross-Sectional Studies, Dry Eye Syndromes, Humans, Occupational Diseases, Pandemics, Quality of Life, Tears},
	issn = {1755-3768},
	doi = {10.1111/aos.15049},
	author = {Fjaervoll, Haakon and Fjaervoll, Ketil and Magno, Morten and Moschowits, Emily and Vehof, Jelle and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1638558,
	title = {Review on the possible pathophysiological mechanisms underlying visual display terminal-associated dry eye disease},
	journal = {Acta Ophthalmol},
	volume = {100},
	number = {8},
	year = {2022},
	month = {2022 Dec},
	pages = {861-877},
	abstract = {BACKGROUND: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described. PURPOSE: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED. METHODS: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated. FINDINGS: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development. CONCLUSION: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED.},
	keywords = {Blinking, Dry Eye Syndromes, Humans, Lacrimal Apparatus, Meibomian Glands, Tears},
	issn = {1755-3768},
	doi = {10.1111/aos.15150},
	author = {Fjaervoll, Ketil and Fjaervoll, Haakon and Magno, Morten and N{\o}land, Sara Tellefsen and Dartt, Darlene A. and Vehof, Jelle and Utheim, Tor P}
}
@article {1748481,
	title = {Purinergic 2X 4 (P2X4), but not P2X7, receptors increase cytosolic [Ca2+] and stimulate mucin secretion in rat conjunctival goblet cells to maintain ocular surface health},
	journal = {Exp Eye Res},
	volume = {235},
	year = {2023},
	month = {2023 Oct},
	pages = {109614},
	abstract = {Ionotropic purinergic receptors (P2XRs) are activated by ATP and ATP analogs. ATP can be released through ATP-permeable channels such as the pannexin hemichannels. Upon activation, the P2XRs become permeable to Ca2+, a potent stimulator of mucin secretion in conjunctival goblet cells (CGCs). The purpose of this study was to investigate the presence and function of P2XRs in CGCs. We also examined the presence of pannexin hemichannels. Rat first passage CGCs were stained with the goblet cell marker anti-cytokeratin 7 antibody and specific antibodies to P2X1-7 receptors and pannexin 1-3. mRNA expression was determined by RT-PCR using primers specific to P2XRs and pannexins. Proteins were identified with Western blotting (WB) using the same antibodies as for immunofluorescence (IF) microscopy. To study receptor function, CGCs were incubated with Fura 2-AM, exposed to agonists and antagonists, and intracellular [Ca2+] ([Ca2+]i) measured. [Ca2+]i was also measured after knock down of P2X4 and P2X7 receptor expression, and when exploiting P2XR specific characteristics. Lastly, mucin secretion was measured after the addition of several P2XR agonists. All P2XRs and pannexins were visualized with IF microscopy, and identified with RT-PCR and WB. [Ca2+]i was significantly increased when stimulated with ATP (10-7-10-4\&nbsp;M). Suramin, a non-selective P2XR antagonist at 10-4\&nbsp;M did not reduce ATP-induced peak [Ca2+]i. The potent P2X7 agonist, BzATP (10-7-10-4\&nbsp;M) increased the [Ca2+]i, although to a lesser extent than ATP. When measuring [Ca2+]i the effect of repeated applications of ATP at 10-5 or 10-6\&nbsp;M the response "desensitized" after 30-60\&nbsp;s. The P2X4 specific antagonist 5-BDBD decreased the P2X4 agonist, 2MeSATP,-induced [Ca2+]i increase. Furthermore, siRNA against the P2X4R, but not the P2X7R, decreased agonist-induced peak [Ca2+]i. ATP (10-5\&nbsp;M), BzATP (10-4\&nbsp;M) and 2MeSATP (10-5\&nbsp;M) induced mucin secretion. We conclude that all seven P2XRs are present in cultured rat CGCs. Of the P2XRs, only activation of the homotrimeric P2X4R appears to increase [Ca2+]i and induce mucin secretion. The P2X4R in CGCs offers a new therapeutic target for protective mucin secretion.},
	keywords = {Adenosine Triphosphate, Animals, Calcium, Goblet Cells, Mucins, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2X7},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2023.109614},
	author = {Fj{\ae}rvoll, Haakon K and Fj{\ae}rvoll, Ketil A and Yang, Menglu and Bair, Jeffrey and Utheim, Tor P and Dartt, Darlene A.}
}
@article {1213811,
	title = {Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis},
	journal = {Lancet Glob Health},
	volume = {5},
	number = {12},
	year = {2017},
	month = {2017 Dec},
	pages = {e1221-e1234},
	abstract = {BACKGROUND: Contemporary data for causes of vision impairment and blindness form an important basis of recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modelling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020. METHODS: In this systematic review and meta-analysis, we analysed published and unpublished population-based data for the causes of vision impairment and blindness from 1980 to 2014. We identified population-based studies published before July 8, 2014, by searching online databases with no language restrictions (MEDLINE from Jan 1, 1946, and Embase from Jan 1, 1974, and the WHO Library Database). We fitted a series of regression models to estimate the proportion of moderate or severe vision impairment (defined as presenting visual acuity of \&lt;6/18 but >=3/60 in the better eye) and blindness (presenting visual acuity of \&lt;3/60 in the better eye) by cause, age, region, and year. FINDINGS: We identified 288 studies of 3 983 541 participants contributing data from 98 countries. Among the global population with moderate or severe vision impairment in 2015 (216{\textperiodcentered}6 million [80\% uncertainty interval 98{\textperiodcentered}5 million to 359{\textperiodcentered}1 million]), the leading causes were uncorrected refractive error (116{\textperiodcentered}3 million [49{\textperiodcentered}4 million to 202{\textperiodcentered}1 million]), cataract (52{\textperiodcentered}6 million [18{\textperiodcentered}2 million to 109{\textperiodcentered}6 million]), age-related macular degeneration (8{\textperiodcentered}4 million [0{\textperiodcentered}9 million to 29{\textperiodcentered}5 million]), glaucoma (4{\textperiodcentered}0 million [0{\textperiodcentered}6 million to 13{\textperiodcentered}3 million]), and diabetic retinopathy (2{\textperiodcentered}6 million [0{\textperiodcentered}2 million to 9{\textperiodcentered}9 million]). Among the global population who were blind in 2015 (36{\textperiodcentered}0 million [12{\textperiodcentered}9 million to 65{\textperiodcentered}4 million]), the leading causes were cataract (12{\textperiodcentered}6 million [3{\textperiodcentered}4 million to 28{\textperiodcentered}7 million]), uncorrected refractive error (7{\textperiodcentered}4 million [2{\textperiodcentered}4 million to 14{\textperiodcentered}8 million]), and glaucoma (2{\textperiodcentered}9 million [0{\textperiodcentered}4 million to 9{\textperiodcentered}9 million]). By 2020, among the global population with moderate or severe vision impairment (237{\textperiodcentered}1 million [101{\textperiodcentered}5 million to 399{\textperiodcentered}0 million]), the number of people affected by uncorrected refractive error is anticipated to rise to 127{\textperiodcentered}7 million (51{\textperiodcentered}0 million to 225{\textperiodcentered}3 million), by cataract to 57{\textperiodcentered}1 million (17{\textperiodcentered}9 million to 124{\textperiodcentered}1 million), by age-related macular degeneration to 8{\textperiodcentered}8 million (0{\textperiodcentered}8 million to 32{\textperiodcentered}1 million), by glaucoma to 4{\textperiodcentered}5 million (0{\textperiodcentered}5 million to 15{\textperiodcentered}4 million), and by diabetic retinopathy to 3{\textperiodcentered}2 million (0{\textperiodcentered}2 million to 12{\textperiodcentered}9 million). By 2020, among the global population who are blind (38{\textperiodcentered}5 million [13{\textperiodcentered}2 million to 70{\textperiodcentered}9 million]), the number of patients blind because of cataract is anticipated to rise to 13{\textperiodcentered}4 million (3{\textperiodcentered}3 million to 31{\textperiodcentered}6 million), because of uncorrected refractive error to 8{\textperiodcentered}0 million (2{\textperiodcentered}5 million to 16{\textperiodcentered}3 million), and because of glaucoma to 3{\textperiodcentered}2 million (0{\textperiodcentered}4 million to 11{\textperiodcentered}0 million). Cataract and uncorrected refractive error combined contributed to 55\% of blindness and 77\% of vision impairment in adults aged 50 years and older in 2015. World regions varied markedly in the causes of blindness and vision impairment in this age group, with a low prevalence of cataract (\&lt;22\% for blindness and 14{\textperiodcentered}1-15{\textperiodcentered}9\% for vision impairment) and a high prevalence of age-related macular degeneration (\&gt;14\% of blindness) as causes in the high-income subregions. Blindness and vision impairment at all ages in 2015 due to diabetic retinopathy (odds ratio 2{\textperiodcentered}52 [1{\textperiodcentered}48-3{\textperiodcentered}73]) and cataract (1{\textperiodcentered}21 [1{\textperiodcentered}17-1{\textperiodcentered}25]) were more common among women than among men, whereas blindness and vision impairment due to glaucoma (0{\textperiodcentered}71 [0{\textperiodcentered}57-0{\textperiodcentered}86]) and corneal opacity (0{\textperiodcentered}54 [0{\textperiodcentered}43-0{\textperiodcentered}66]) were more common among men than among women, with no sex difference related to age-related macular degeneration (0{\textperiodcentered}91 [0{\textperiodcentered}70-1{\textperiodcentered}14]). INTERPRETATION: The number of people affected by the common causes of vision loss has increased substantially as the population increases and ages. Preventable vision loss due to cataract (reversible with surgery) and refractive error (reversible with spectacle correction) continue to cause most cases of blindness and moderate or severe vision impairment in adults aged 50 years and older. A large scale-up of eye care provision to cope with the increasing numbers is needed to address avoidable vision loss. FUNDING: Brien Holden Vision Institute.},
	issn = {2214-109X},
	doi = {10.1016/S2214-109X(17)30393-5},
	author = {Flaxman, Seth R and Bourne, Rupert R A and Resnikoff, Serge and Ackland, Peter and Braithwaite, Tasanee and Cicinelli, Maria V and Das, Aditi and Jonas, Jost B and Keeffe, Jill and Kempen, John H and Leasher, Janet and Limburg, Hans and Naidoo, Kovin and Pesudovs, Konrad and Silvester, Alex and Stevens, Gretchen A and Tahhan, Nina and Wong, Tien Y and Taylor, Hugh R and Vision Loss Expert Group of the Global Burden of Disease Study}
}
@article {1677716,
	title = {High-efficiency purification of divergent AAV serotypes using AAVX affinity chromatography},
	journal = {Mol Ther Methods Clin Dev},
	volume = {28},
	year = {2023},
	month = {2023 Mar 09},
	pages = {146-159},
	abstract = {The adeno-associated viral vector (AAV) provides a safe and efficient gene therapy platform with several approved products that have marked therapeutic impact for patients. However, a major bottleneck in the development and commercialization of AAV remains the efficiency, cost, and scalability of AAV production. Chromatographic methods have the potential to allow purification at increased scales and lower cost but often require optimization specific to each serotype. Here, we demonstrate that the POROS CaptureSelect AAVX affinity resin efficiently captures a panel of 15 divergent AAV serotypes, including the commonly used AAV2, AAV8, AAV9, PHP.B, and Anc80. We also find that AAVX resin can be regenerated repeatedly without loss of efficiency or carry-over contamination. While AAV preps purified with AAVX showed a higher fraction of empty capsids than preps purified using iodixanol ultracentrifugation, the potency of the AAVX purified vectors was comparable with that of iodixanol purified vectors both in\&nbsp;vitro and in\&nbsp;vivo. Finally, optimization of the purification protocol resulted in a process with an overall efficiency of 65\%-80\% across all scales and AAV serotypes tested. These data establish AAVX affinity chromatography as a versatile and efficient method for purification of a broad range of AAV serotypes.},
	issn = {2329-0501},
	doi = {10.1016/j.omtm.2022.12.009},
	author = {Florea, Michael and Nicolaou, Fotini and Pacouret, Simon and Zinn, Eric M and Sanmiguel, Julio and Andres-Mateos, Eva and Unzu, Carmen and Wagers, Amy J and Vandenberghe, Luk H}
}
@article {1623359,
	title = {Prevalence of Diabetic Eye Diseases in American Indians and Alaska Natives (AI/AN) as Identified by the Indian Health Service{\textquoteright}s National Teleophthalmology Program Using Ultrawide Field Imaging (UWFI)},
	journal = {Ophthalmic Epidemiol},
	volume = {29},
	number = {6},
	year = {2022},
	month = {2022 Dec},
	pages = {672-680},
	abstract = {PURPOSE: Estimates of diabetic eye disease in American Indian and Alaska Natives (AI/AN) vary over time, region, and methods. This article reports recent prevalence of diabetic retinopathy (DR) and diabetic macular edema (DME) in AI/AN served by the Indian Health Services{\textquoteright} (IHS) teleophthalmology program, as identified using ultrawide field imaging (UWFI). METHODS: This was a retrospective analysis of 2016-2019 clinical data (n\&nbsp;=\&nbsp;53,900). UWF images were acquired by certified imagers using a validated protocol, and graded by licensed, certified optometrists supervised by an ophthalmologist. Graders evaluated the extent/severity of retinal lesions in comparison to standard photographs. DR lesions predominantly in any peripheral field were considered "predominantly peripheral lesions" (PPL). The analyses calculated prevalence of any DR, any DME, DR and DME severity, sight-threatening disease, and PPL. RESULTS: Patients averaged 56\&nbsp;years of age with a 68\&nbsp;mmol/mol A1c and 55\% had had diabetes for 5+\&nbsp;years. Prevalence of any DR, any DME, and sight-threatening disease was 28.6\%, 3.0\%, and 3.0\%. In patients with mild nonproliferative DR, PPL was seen in 25.3\%. PPL suggested a more severe level of DR in 8.7\% of patients. DR increased with age. DME decreased with age. Males and patients in the Nashville IHS area had more diabetic eye disease. CONCLUSION: AI/AN have a high burden of diabetes and its complications. The IHS is resource-constrained, making accurate disease estimates necessary for resource allocation and budget justifications to Congress. These data update the estimates of diabetic eye disease in Indian Country and suggest that UWFI identifies early DR.},
	keywords = {Alaskan Natives, Diabetes Mellitus, Diabetic Retinopathy, Female, Humans, Macular Edema, Male, Ophthalmology, Photography, Prevalence, Retrospective Studies, Telemedicine, United States, United States Indian Health Service},
	issn = {1744-5086},
	doi = {10.1080/09286586.2021.1996611},
	author = {Fonda, Stephanie Jo and Bursell, Sven-Erik and Lewis, Drew G and Clary, Dawn and Shahon, Dara and Silva, Paolo S}
}
@article {1677681,
	title = {Incidence and Progression of Diabetic Retinopathy in American Indian and Alaska Native Individuals Served by the Indian Health Service, 2015-2019},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {4},
	year = {2023},
	month = {2023 Apr 01},
	pages = {366-375},
	abstract = {IMPORTANCE: Estimates of diabetic retinopathy (DR) incidence and progression in American Indian and Alaska Native individuals are based on data from before 1992 and may not be informative for strategizing resources and practice patterns. OBJECTIVE: To examine incidence and progression of DR in American Indian and Alaska Native individuals. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study conducted from January 1, 2015, to December 31, 2019, and included adults with diabetes and no evidence of DR or mild nonproliferative DR (NPDR) in 2015 who were reexamined at least 1 time during the 2016 to 2019 period. The study setting was the Indian Health Service (IHS) teleophthalmology program for diabetic eye disease. EXPOSURE: Development of new DR or worsening of mild NPDR in American Indian and Alaska Native individuals with diabetes. MAIN OUTCOMES AND MEASURES: Outcomes were any increase in DR, 2 or more (2+) step increases, and overall change in DR severity. Patients were evaluated with nonmydriatic ultra-widefield imaging (UWFI) or nonmydriatic fundus photography (NMFP). Standard risk factors were included. RESULTS: The total cohort of 8374 individuals had a mean (SD) age of 53.2 (12.2) years and a mean (SD) hemoglobin A1c level of 8.3\% (2.2\%) in 2015, and 4775 were female (57.0\%). Of patients with no DR in 2015, 18.0\% (1280 of 7097) had mild NPDR or worse in 2016 to 2019, and 0.1\% (10 of 7097) had PDR. The incidence rate from no DR to any DR was 69.6 cases per 1000 person-years at risk. A total of 6.2\% of participants (441 of 7097) progressed from no DR to moderate NPDR or worse (ie, 2+ step increase; 24.0 cases per 1000 person-years at risk). Of patients with mild NPDR in 2015, 27.2\% (347 of 1277) progressed to moderate NPDR or worse in 2016 to 2019, and 2.3\% (30 of 1277) progressed to severe NPDR or worse (ie, 2+ step progression). Incidence and progression were associated with expected risk factors and evaluation with UWFI. CONCLUSIONS AND RELEVANCE: In this cohort study, the estimates of DR incidence and progression were lower than those previously reported for American Indian and Alaska Native individuals. The results suggest extending the time between DR re-evaluations for certain patients in this population, if follow-up compliance and visual acuity outcomes are not jeopardized.},
	keywords = {Adult, American Indian or Alaska Native, Cohort Studies, Diabetes Mellitus, Diabetic Retinopathy, Female, Humans, Incidence, Male, Middle Aged, Ophthalmology, Retrospective Studies, Telemedicine, United States, United States Indian Health Service},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.0167},
	author = {Fonda, Stephanie J and Bursell, Sven-Erik and Lewis, Drew G and Clary, Dawn and Shahon, Dara and Cavallerano, Jerry}
}
@article {1642023,
	title = {The relation of the multifocal electroretinographic response to macular layer volume},
	journal = {Doc Ophthalmol},
	year = {2022},
	month = {2022 May 10},
	abstract = {PURPOSE: To determine the association of the multifocal electroretinographic (mfERG) response amplitude with the volumes of the inner, postreceptor, and photoreceptor retinal layers in the region stimulated by each mfERG element. METHODS: Sixteen healthy, young adult control subjects were studied. Each of the 103 hexagonal elements of the standard, scaled mfERG were aligned, where possible, with patches of retina imaged using optical coherence tomography. Stimuli falling on the fovea and on the optic nerve head were excluded. Linear mixed-effects modeling was then used to derive estimated coefficients (voltage/volume) for the mfERG response throughout the full 80\&nbsp;ms standard epoch. The resulting predicted response amplitudes originating in each layer were then compared to pharmacologically "dissected" mfERGs obtained from other studies in monkey eyes. RESULTS: Across the duration of the response, the amplitude of the modeled contribution from (1)\&nbsp;the inner retina was small-to-modest, (2)\&nbsp;the postreceptor retina was larger and contained two prominent peaks, and (3)\&nbsp;the photoreceptor response was the largest and most closely paralleled the overall (i.e., intact) response, including late-appearing oscillations. The significance of each layer{\textquoteright}s contribution was greatest when the absolute amplitude of that layer{\textquoteright}s response was largest. The contribution of the inner retina was maximally significant in the interval between the prominent troughs and peaks of the intact response. The contributions of the postreceptor and photoreceptor responses were maximally significant at the prominent troughs and peaks of the intact response. CONCLUSIONS: The results of the model were in good overall agreement with previous interpretations of the cellular contributions to the mfERG. There was also fair agreement with pharmacologically dissected monkey mfERG responses. Thus, the estimations of the contributions of the retinal layers to the mfERG so produced appeared plausible.},
	issn = {1573-2622},
	doi = {10.1007/s10633-022-09873-z},
	author = {Fonseca, Mariana I and Nouck-A-Nwal, Alexandra and Ambrosio, Lucia and Altschwager, Pablo and Hansen, Ronald M and Fulton, Anne B and Akula, James D}
}
@article {1319465,
	title = {Pseudohemangioma in Nonarteritic Anterior Ischemic Optic Neuropathy},
	journal = {Ophthalmology},
	volume = {125},
	number = {6},
	year = {2018},
	month = {2018 Jun},
	pages = {903},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.01.029},
	author = {Fortin, Elizabeth and Gaier, Eric D}
}
@article {1359927,
	title = {Ocular myasthenia gravis: an update on diagnosis and treatment},
	journal = {Curr Opin Ophthalmol},
	volume = {29},
	number = {6},
	year = {2018},
	month = {2018 Nov},
	pages = {477-484},
	abstract = {PURPOSE OF REVIEW: Myasthenia gravis is an autoimmune disease that commonly affects the palpebral and extraocular muscles. Ocular myasthenia gravis (OMG) is a variant of the disease that is confined to the ocular muscles but frequently becomes generalized over time. The diagnosis of OMG is often challenging but both clinical and laboratory findings are helpful in confirming the clinical suspicion. This review provides an update on the diagnostic approach and therapeutic options for OMG. RECENT FINDINGS: Antimuscle-specific tyrosine kinase and LDL-related receptor-related protein 4 are newly available serologic testing for myasthenia gravis that can help in increasing the diagnostic sensitivity of OMG. They should be included to the diagnostic algorithm of OMG in appropriate clinical situations. SUMMARY: OMG remains a primarily clinical diagnosis, but recent advances in laboratory testing can improve the diagnostic accuracy and should be used in appropriate clinical settings. The mainstay of treatment for OMG has not significantly changed over the past years, but the increasing availability of steroid-sparing agents improved the disease control while minimizing steroid-induced complications.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000526},
	author = {Fortin, Elizabeth and Cestari, Dean M and Weinberg, David H}
}
@article {705066,
	title = {Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility.},
	journal = {PLoS One},
	volume = {11},
	number = {5},
	year = {2016},
	month = {2016},
	pages = {e0155214},
	abstract = {The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sj{\"o}gren{\textquoteright}s syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52\% women and 48\% men) with DED were included. Patient demographics were: 0 to 19 years (1\%), 20 to 39 (25\%), 40 to 59 (34\%), 60 to 79 (35\%) and 80 to 99 (5\%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23\% of the patients. Female sex was more common among patients with xerostomia (81\%) than among non-xerostomia patients (44\%; P\&lt;0.001). Patients with xerostomia (60 {\textpm} 15 years) were older than those without xerostomia (51 {\textpm} 17; P\&lt;0.001). The use of prescription drugs was more prevalent among xerostomia patients (65\%) than among non-xerostomia patients (35\%; P\&lt;0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 {\textpm} 10.0) than those without xerostomia (12.9 {\textpm} 8.0; P\&lt;0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 {\textpm} 0.7) than those without xerostomia (0.7 {\textpm} 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0155214},
	author = {Fostad, Ida G and Eidet, Jon R and Utheim, Tor P and R{\ae}der, Sten and Lagali, Neil S and Messelt, Edvard B and Dartt, Darlene A.}
}
@article {1364606,
	title = {Biopsy harvesting site and distance from the explant affect conjunctival epithelial phenotype ex vivo},
	journal = {Exp Eye Res},
	volume = {104},
	year = {2012},
	month = {2012 Nov},
	pages = {15-25},
	abstract = {The purpose of the study was to investigate if the number of goblet cells expanded ex vivo from a conjunctival explant is affected by the biopsy harvesting site on the conjunctiva and the distance from the explant. Conjunctival explants from six regions: superior and inferior bulbus, fornix, and tarsus of male Sprague-Dawley rats were grown in RPMI 1640 with 10\% fetal bovine serum on coverslips for eight days. Histochemical and immunofluorescent staining of goblet (CK-7/UEA-1/MUC5AC), stratified squamous, non-goblet (CK-4), proliferating (PCNA) and progenitor (ABCG2) cells were analyzed by epifluorescence and laser confocal microscopy. Outgrowth was measured with NIH ImageJ. For statistical analysis the Mann-Whitney test and Spearman{\textquoteright}s rank-order correlation test were used. Cultures from superior and inferior fornix contained the most goblet cells as indicated by the presence of CK-7+, UEA-1+ and MUC5AC+ cells. Superior and inferior forniceal cultures displayed 60.8\% {\textpm} 9.2\% and 64.7\% {\textpm} 6.7\% CK-7+ cells, respectively, compared to the superior tarsal (26.6\% {\textpm} 8.4\%; P \&lt; 0.05), superior bulbar (31.0\% {\textpm} 4.0\%; P \&lt; 0.05), inferior bulbar (38.5\% {\textpm} 9.3\%; P \&lt; 0.05) and inferior tarsal cultures (27.7\% {\textpm} 8.3\%; P \&lt; 0.05). While 28.4\% {\textpm} 6.3\% of CK-7+ goblet cells co-labeled with PCNA, only 7.4\% {\textpm} 1.6\% of UEA-1+ goblet cells did (P \&lt; 0.01). CK-7+ goblet cells were located at a lower concentration close to the explant (39.8\% {\textpm} 3.1\%) compared to near the leading edge (58.2\% {\textpm} 4.5\%; P \&lt; 0.05). Both markers for goblet cell secretory product (UEA-1 and MUC5AC), however, displayed the opposite pattern with a higher percentage of positive cells close to the explant than near the leading edge (P \&lt; 0.05). The percentage of CK-4+ cells was higher near the explant compared to near the leading edge (P \&lt; 0.01). The percentage of CK-7+ goblet cells in the cultures did not correlate with the outgrowth size (r(s) = -0.086; P = 0.435). The percentage of UEA-1+ goblet cells correlated negatively with outgrowth size (r(s) = -0.347; P \&lt; 0.01), whereas the percentage of CK-4+ cells correlated positively with the outgrowth size (r(s) = 0.473; P \&lt; 0.05). We conclude that forniceal explants yield the highest number of goblet cells ex vivo and thereby seem to be optimal for goblet cell transplantation. We also suggest that CK-7+/UEA-1- cells represent highly proliferative immature goblet cells. These cells could be important during conjunctival migration as they are mostly located close to the leading edge and their density does not decrease with increasing outgrowth size.},
	keywords = {Animals, ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters, Biomarkers, Biopsy, Cell Count, Cell Proliferation, Cells, Cultured, Conjunctiva, Goblet Cells, Keratins, Male, Microscopy, Confocal, Mucin 5AC, Phenotype, Plant Lectins, Proliferating Cell Nuclear Antigen, Rats, Rats, Sprague-Dawley, Tissue and Organ Harvesting},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2012.09.007},
	author = {Fostad, I G and Eidet, J R and Shatos, M A and Utheim, T P and Utheim, O A and Raeder, S and Dartt, D A}
}
@article {504006,
	title = {The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {1},
	year = {2016},
	month = {2016 Jan-Feb},
	pages = {1-17},
	abstract = {Ocular inflammatory disease is a leading cause of vision loss worldwide. Uveitis encompasses a wide spectrum of pathology, both with respect to its etiology and the anatomic location within the eye. Inflammation can be confined to the eye and may also be seen systemically. The cornerstone of management of ocular inflammatory disease historically has been corticosteroids, which are invaluable in the immediate control of inflammation; however, corticosteroids are inappropriate for long-term use as they are associated with a wide array of toxic side effects. As we continue to learn more about the various etiologies and elucidate the basic science pathways and mechanisms of action that cause intraocular inflammation, new therapeutic approaches have evolved. They include employment of immunomodulatory agents (corticosteroid-sparing therapies) that have expanded our treatment options for these vision-threatening diseases. These pharmacologics provide therapy for ocular and systemic inflammation in an individualized, patient-tailored, stepladder approach with the ultimate goal of durable, corticosteroid-free remission. We review the preferred practice patterns of a tertiary care center specializing in ocular inflammatory disease.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2015.07.001},
	author = {Foster, C Stephen and Kothari, Srishti and Anesi, Stephen D and Vitale, Albert T and Chu, David and Metzinger, Jamie Lynne and Cer{\'o}n, Olga}
}
@article {1629443,
	title = {Isoform-dependent lysosomal degradation and internalization of apolipoprotein E requires autophagy proteins},
	journal = {J Cell Sci},
	volume = {135},
	number = {2},
	year = {2022},
	month = {2022 01 15},
	abstract = {The human apolipoprotein E4 isoform (APOE4) is the strongest genetic risk factor for late-onset Alzheimer{\textquoteright}s disease (AD), and lysosomal dysfunction has been implicated in AD pathogenesis. We found, by examining cells stably expressing each APOE isoform, that APOE4 increases lysosomal trafficking, accumulates in enlarged lysosomes and late endosomes, alters autophagic flux and the abundance of autophagy proteins and lipid droplets, and alters the proteomic contents of lysosomes following internalization. We investigated APOE-related lysosomal trafficking further in cell culture, and found that APOE from the post-Golgi compartment is degraded through autophagy. We found that this autophagic process requires the lysosomal membrane protein LAMP2 in immortalized neuron-like and hepatic cells, and in mouse brain tissue. Several macroautophagy-associated proteins were also required for autophagic degradation and internalization of APOE in hepatic cells. The dysregulated autophagic flux and lysosomal trafficking of APOE4 that we observed suggest a possible novel mechanism that might contribute to AD pathogenesis. This article has an associated First Person interview with the first author of the paper.},
	issn = {1477-9137},
	doi = {10.1242/jcs.258687},
	author = {Fote, Gianna M and Geller, Nicolette R and Efstathiou, Nikolaos E and Hendricks, Nathan and Vavvas, Demetrios G and Reidling, Jack C and Thompson, Leslie M and Steffan, Joan S}
}
@article {1504067,
	title = {Aged Mice Exhibit Severe Exacerbations of Dry Eye Disease with an Amplified Memory Th17 Cell Response},
	journal = {Am J Pathol},
	volume = {190},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {1474-1482},
	abstract = {The prevalence as well as the severity of dry eye disease increase with age. Memory T helper 17 (Th17) cells\&nbsp;(CD4IL-17ACD44) drive the chronic and relapsing course of dry eye disease. Here, we investigated the contribution of memory Th17 cells to age-related dry eye disease, and evaluated memory Th17 cell depletion with anti-IL-15 antibody as a strategy to abrogate the severe exacerbations of dry eye\&nbsp;disease observed in aged mice. After initial exposure to desiccating stress, aged mice maintained higher frequencies of memory Th17 cells in the draining lymph nodes relative to young mice. Upon secondary exposure to desiccating stress, aged mice developed more severe corneal epitheliopathy than young mice, which is associated with increased local frequencies of Th17 cells (CD4IL-17A). Treatment with anti-IL-15 antibody decreased the enlarged memory Th17 pool in aged mice to frequencies comparable with young mice. Furthermore, anti-IL-15-treated mice showed significantly reduced conjunctival infiltration of Th17 cells and lower corneal fluorescein staining scores compared with saline-treated control mice. Our data suggest that age-related increases in the memory Th17 compartment predispose aged mice toward the development of severe corneal epithelial disease after exposure to a dry environment. Selectively targeting memory Th17 cells may be a viable therapeutic approach in the treatment of age-related dry eye disease.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.03.016},
	author = {Foulsham, William and Mittal, Sharad K and Taketani, Yukako and Chen, Yihe and Nakao, Takeshi and Chauhan, Sunil K and Dana, Reza}
}
@article {1213816,
	title = {High Altitude-associated Changes in Intraocular Pressure Abrogated by Trabeculectomy},
	journal = {J Glaucoma},
	volume = {26},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {957-960},
	abstract = {PURPOSE: To highlight the effect of ascent to high altitude on intraocular pressure (IOP) in a patient with primary open-angle glaucoma, who had previously undergone trabeculectomy in 1 eye. METHODS: Case report. RESULTS: A 66-year-old mountaineer with primary open-angle glaucoma and previous right trabeculectomy performed self-tonometry using a rebound tonometer (Icare HOME) before and during an expedition in the Himalaya. In the nonoperated eye, there was a statistically significant increase in IOP as the patient ascended to 5000 m over 8 days (R=0.790, P=0.001), consistent with recent literature. IOP increased by 1.73 mm Hg with each 1000 m increase in altitude. In the trabeculectomized eye there was no significant increase in IOP (R=0.219, P=0.172). CONCLUSIONS: Filtration surgery may be protective against IOP fluctuations associated with ascent to high altitude. Self-tonometry complements standard glaucoma care by providing opportunities for IOP monitoring outside office hours and in remote locations.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000713},
	author = {Foulsham, William and Tatham, Andrew J}
}
@article {1445340,
	title = {Thrombospondin-1 in ocular surface health and disease},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Jun 04},
	abstract = {Thrombospondin 1 (TSP-1) is an extracellular matrix protein that interacts with a wide array of ligands including cell receptors, growth factors, cytokines and proteases to regulate various physiological and pathological processes. Constitutively expressed by certain ocular surface tissues (e.g. corneal and conjunctival epithelium), TSP-1 expression is modulated during ocular surface inflammation. TSP-1 is an important activator of latent TGF-β, serving to promote the immunomodulatory and wound healing functions of TGF-β. Mounting research has deepened our understanding of how TSP-1 expression (and lack thereof) contributes to ocular surface homeostasis and disease. Here, we review current knowledge of the function of TSP-1 in dry eye disease, ocular allergy, angiogenesis/lymphangiogenesis, corneal transplantation, corneal wound healing and infectious keratitis.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.06.001},
	author = {Foulsham, William and Dohlman, Thomas H and Mittal, Sharad K and Taketani, Yukako and Singh, Rohan Bir and Masli, Sharmila and Dana, Reza}
}
@article {1445328,
	title = {The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 Jun 13},
	pages = {8617},
	abstract = {Adenosine triphosphate (ATP) is released into the extracellular environment during transplantation, and acts via purinergic receptors to amplify the alloimmune response. Here, using a well-established murine model of allogeneic corneal transplantation, we investigated the immunomodulatory mechanisms of the purinergic receptor antagonist oxidized ATP (oATP). Corneal transplantation was performed using C57BL/6 donors and BALB/c hosts. oATP or sterile saline was administered via intraperitoneal injection for 2 weeks postoperatively. Frequencies of CD45 leukocytes, CD11bMHCII antigen presenting cells (APCs), CD4IFN-γ effector Th1 cells and CD4Foxp3 regulatory T cells (Tregs) were evaluated by flow cytometry. Slit-lamp microscopy was performed weekly for 8 weeks to evaluate graft opacity and determine transplant rejection. Treatment with oATP was shown to significantly reduce graft infiltration of CD45 leukocytes, decrease APC maturation and suppress effector Th1 cell generation relative to saline-treated control. No difference in Treg frequencies or Foxp3 expression was observed between the oATP-treated and control groups. Finally, oATP treatment was shown to reduce graft opacity and increase graft survival. This report demonstrates that oATP limits the alloimmune response by regulating APC maturation and suppressing the generation of alloreactive Th1 immunity.},
	issn = {2045-2322},
	doi = {10.1038/s41598-019-44973-y},
	author = {Foulsham, William and Mittal, Sharad K and Nakao, Takeshi and Coco, Giulia and Taketani, Yukako and Chauhan, Sunil K and Dana, Reza}
}
@article {1309974,
	title = {When Clarity Is Crucial: Regulating Ocular Surface Immunity},
	journal = {Trends Immunol},
	volume = {39},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {288-301},
	abstract = {The ocular surface is a unique mucosal immune compartment in which anatomical, physiological, and immunological features act in concert to foster a particularly tolerant microenvironment. These mechanisms are vital to the functional competence of the eye, a fact underscored by the devastating toll of excessive inflammation at the cornea - blindness. Recent data have elucidated the contributions of specific anatomical components, immune cells, and soluble immunoregulatory factors in promoting homeostasis at the ocular surface. We highlight research trends at this distinctive mucosal barrier and identify crucial gaps in our current knowledge.},
	issn = {1471-4981},
	doi = {10.1016/j.it.2017.11.007},
	author = {Foulsham, William and Coco, Giulia and Amouzegar, Afsaneh and Chauhan, Sunil K and Dana, Reza}
}
@article {1417558,
	title = {ALTITUDE-ASSOCIATED INTRAOCULAR PRESSURE CHANGES IN A GAS-FILLED EYE},
	journal = {Retin Cases Brief Rep},
	volume = {15},
	number = {5},
	year = {2021},
	month = {2021 Sep 01},
	pages = {564-567},
	abstract = {PURPOSE: Intraocular gases are commonly used in vitreoretinal surgery. Patients are routinely advised against air travel before the complete absorption of intraocular gas. Consequently, reports on air travel in patients with large intraocular gas bubbles are highly unusual. Here, we report the intraocular pressure changes of a patient ascending to an altitude of 2,600 feet in a helicopter with a 50\% fill perfluoropropane (C3F8) gas bubble in his left eye. METHODS: Case report and literature review. RESULTS: A 61-year-old male patient underwent pars plana vitrectomy for a rhegmatogenous retinal detachment, with fluid-gas exchange using 16\% C3F8. With a 50\% fill bubble in the left eye, the patient took a short helicopter trip ascending to a maximum altitude of 2,600 feet. Before take-off, intraocular pressure in the operated eye was 14 mmHg. The average increase in intraocular pressure was 10.8 mmHg per 1,000 feet of ascent, with a maximum recorded intraocular pressure of 42 mmHg. The patient denied both ocular pain and loss of vision but did report changes in the appearance of the gas bubble meniscus at 2,100 feet. CONCLUSION: Short-term low-altitude air travel may be tolerated by some patients with intraocular gas in situ. Further studies are required to define the conditions by which patients with gas bubbles may fly safely.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000852},
	author = {Foulsham, William and Chen, Xiaohong N and Vavvas, Demetrios G}
}
@article {1195281,
	title = {Review: The function of regulatory T cells at the ocular surface},
	journal = {Ocul Surf},
	volume = {15},
	number = {4},
	year = {2017},
	month = {2017 Oct},
	pages = {652-659},
	abstract = {Regulatory T cells (Tregs) are critical modulators of immune homeostasis. Tregs maintain peripheral tolerance to self-antigens, thereby preventing autoimmune disease. Furthermore, Tregs suppress excessive immune responses deleterious to the host. Recent research has deepened our understanding of how Tregs function at the ocular surface. This manuscript describes the classification, the immunosuppressive mechanisms, and the phenotypic plasticity of Tregs. We review the contribution of Tregs to ocular surface autoimmune disease, as well as the function of Tregs in allergy and infection at the ocular surface. Finally, we review the role of Tregs in promoting allotolerance in corneal transplantation.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.05.013},
	author = {Foulsham, William and Marmalidou, Anna and Amouzegar, Afsaneh and Coco, Giulia and Chen, Yihe and Dana, Reza}
}
@article {836826,
	title = {Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach.},
	journal = {Am J Ophthalmol},
	volume = {168},
	year = {2016},
	month = {2016 Aug},
	pages = {183-90},
	abstract = {PURPOSE: To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. DESIGN: Modified Delphi process. METHODS: A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75\% of experts in agreement. RESULTS: There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. CONCLUSIONS: Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.05.013},
	author = {Fox, Austin R and Gordon, Lynn K and Heckenlively, John R and Davis, Janet L and Goldstein, Debra A and Lowder, Careen Y and Nussenblatt, Robert B and Butler, Nicholas J and Dalal, Monica and Jayasundera, Thiran and Smith, Wendy M and Lee, Richard W and Adamus, Grazyna and Chan, Chi-Chao and Hooks, John J and Morgans, Catherine W and Detrick, Barbara and Sen, H Nida}
}
@article {1798506,
	title = {Identification of pathogenic genetic variants in patients with acquired early-onset bilateral cataracts using next-generation sequencing},
	journal = {J AAPOS},
	volume = {28},
	number = {1},
	year = {2024},
	month = {2024 Feb},
	pages = {103808},
	abstract = {BACKGROUND: Acquired early-onset bilateral cataracts can result from systemic etiologies or genetic disorders.

METHODS: In this observational study, we analyzed individuals 18 months to 35 years of age with acquired bilateral cataracts via a next-generation sequencing panel of 66 genes to identify disease-causing genetic variants.

RESULTS: Of 347 patients enrolled, 313 (90.2\%) were \&lt;19 years (median, 8 years). We identified 74 pathogenic or likely pathogenic variants in 69 patients. Of the variants, we observed 64 single nucleotide variants (SNV) in 24 genes and 10 copy number variants (CNV) of varying size and genomic location. SNVs in crystallin genes were most common, accounting for 27.0\% of all variants (20 of 74). Of those, recurrent variants included known cataract-causing variants CRYBA1 c.215+1G\&gt;A, observed in 3 patients, and CRYBA1 c.272_274delGAG, CRYBB2 c.463C\&gt;T and c.562C\&gt;T, and CRYAA c.62G\&gt;A, each observed in 2 patients. In 5 patients, we identified CNV deletions ranging from 1.32-2.41 Mb in size associated with 1q21.1 microdeletion syndrome. Biallelic variants in CYP27A1 were identified in two siblings, one as part of targeted follow-up family testing, who were subsequently diagnosed with cerebrotendinous xanthomatosis, a rare but treatable autosomal recessive disease that often presents with acquired early-onset bilateral cataracts.

CONCLUSIONS: This study demonstrates the utility of genetic testing in individuals with acquired early-onset bilateral cataracts to help clarify etiology. Identification of causative genetic variants can inform patient management and facilitate genetic counseling by identifying genetic conditions with risk of recurrence in families.},
	keywords = {Cataract, Genetic Testing, High-Throughput Nucleotide Sequencing, Humans, Pedigree, Xanthomatosis, Cerebrotendinous},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.11.011},
	author = {Fox, Jamie C and Dutta, Rana and Nihalani, Bharti R and Ponte, Amy and Talsness, Dana M and VanderVeen, Deborah K and Steiner, Robert D and Freedman, Sharon F}
}
@article {705071,
	title = {Distal retinal ganglion cell axon transport loss and activation of p38 MAPK stress pathway following VEGF-A antagonism.},
	journal = {Cell Death Dis},
	volume = {7},
	year = {2016},
	month = {2016},
	pages = {e2212},
	abstract = {There is increasing evidence that VEGF-A antagonists may be detrimental to neuronal health following ocular administration. Here we investigated firstly the effects of VEGF-A neutralization on retinal neuronal survival in the Ins2(Akita) diabetic and JR5558 spontaneous choroidal neovascularization (CNV) mice, and then looked at potential mechanisms contributing to cell death. We detected elevated apoptosis in the ganglion cell layer in both these models following VEGF-A antagonism, indicating that even when vascular pathologies respond to treatment, neurons are still vulnerable to reduced VEGF-A levels. We observed that retinal ganglion cells (RGCs) seemed to be the cells most susceptible to VEGF-A antagonism, so we looked at anterograde transport in these cells, due to their long axons requiring optimal protein and organelle trafficking. Using cholera toxin B-subunit tracer studies, we found a distal reduction in transport in the superior colliculus following VEGF-A neutralization, which occurred prior to net RGC loss. This phenomenon of distal transport loss has been described as a feature of early pathological changes in glaucoma, Alzheimer{\textquoteright}s and Parkinson{\textquoteright}s disease models. Furthermore, we observed increased phosphorylation of p38 MAPK and downstream Hsp27 stress pathway signaling in the retinas from these experiments, potentially providing a mechanistic explanation for our findings. These experiments further highlight the possible risks of using VEGF-A antagonists to treat ocular neovascular disease, and suggest that VEGF-A may contribute to the maintenance and function of axonal transport in neurons of the retina.},
	issn = {2041-4889},
	doi = {10.1038/cddis.2016.110},
	author = {Foxton, R and Osborne, A and Martin, K R and Ng, Y-S and Shima, D T}
}
@article {1490463,
	title = {Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading},
	journal = {Ophthalmology},
	volume = {127},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {240-248},
	abstract = {PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.09.018},
	author = {Francis, Jasmine H and Berry, Duncan and Abramson, David H and Barker, Christopher A and Bergstrom, Chris and Demirci, Hakan and Engelbert, Michael and Grossniklaus, Hans and Hubbard, Baker and Iacob, Codrin E and Jaben, Korey and Kurli, Madhavi and Postow, Michael A and Wolchok, Jedd D and Kim, Ivana K and Wells, Jill R}
}
@article {1549016,
	title = {Immune Checkpoint Inhibitor-Associated Optic Neuritis},
	journal = {Ophthalmology},
	volume = {127},
	number = {11},
	year = {2020},
	month = {2020 11},
	pages = {1585-1589},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.05.003},
	author = {Francis, Jasmine H and Jaben, Korey and Santomasso, Bianca D and Canestraro, Julia and Abramson, David H and Chapman, Paul B and Berkenstock, Meghan and Aronow, Mary E}
}
@article {1651360,
	title = {Low-dose proton radiotherapy for pediatric choroidal hemangioma: A case series},
	journal = {Pediatr Blood Cancer},
	year = {2022},
	author = {Franco, JJ and Liu, KX and Ioakeim-Ioannidou, M and Davila, JR and Chen, Y.L. and Kim, IK and Gragoudas, ES and Mukai, S and MacDonald, SM}
}
@article {1661850,
	title = {Low-dose proton radiotherapy for pediatric choroidal hemangioma: A case series},
	journal = {Pediatr Blood Cancer},
	volume = {69},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {e29925},
	abstract = {Management of pediatric choroidal hemangioma complicated by large exudative retinal detachment can be challenging, with few options available. Limited data have been published on outcomes following proton radiotherapy (PRT) for management of these patients. In this retrospective case series, nine patients were treated with a low-dose PRT regimen of 20\&nbsp;Gy(relative biological effectiveness [RBE]) in 10 fractions, and two were treated with 15\&nbsp;Gy(RBE) in four fractions. Visual acuity improved in seven patients (64\%) and remained stable in the remaining four (36\%). In patients with imaging follow-up (10 patients), subretinal fluid resolved in nine patients (90\%) and tumor thickness decreased or remained stable in 10 (100\%). Complications were observed in eight of 11 patients (73\%). One patient developed grade 2 cataract; otherwise, no grade >=2 complications were observed.},
	keywords = {Child, Choroid Neoplasms, Hemangioma, Humans, Protons, Retrospective Studies, Sturge-Weber Syndrome},
	issn = {1545-5017},
	doi = {10.1002/pbc.29925},
	author = {Franco, Jovany J and Liu, Kevin X and Ioakeim-Ioannidou, Myrsini and Davila, Jose R and Chen, Yen-Lin and Kim, Ivana K and Gragoudas, Evangelos S and Mukai, Shizuo and MacDonald, Shannon M}
}
@article {1528431,
	title = {Survival of the fittest: phacoemulsification outcomes in four corneal transplants by Dr Ramon Castroviejo},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {1076-1081},
	abstract = {AIM: To evaluate and report the outcomes following phacoemulsification on four eyes, 45\&nbsp;years or more after corneal transplantation. METHODS: A retrospective case series of four eyes in three patients (P1, P2, P3), undergoing phacoemulsification at least 45\&nbsp;years after corneal transplantation by Dr Ramon Castroviejo. Corneal graft survival outcome measures included central corneal thickness (CCT), best-corrected visual acuity (BCVA), corneal clarity and endothelial cell count (ECC). RESULTS: Phacoemulsification was successfully completed in all four cases with no instances of graft failure during the postoperative follow-up period, which ranged from 17 months to 76\&nbsp;months. At the conclusion of the follow-up period, all four grafts remained clear, and BCVA remained better than or similar to preoperative values. Long-term follow-up revealed no meaningful changes in CCT after phacoemulsification. All but one case experienced a decrease in ECC, with ECC values in the four cases ranging from 538 cells/mm2 to 1436 cells/mm2 at the conclusion of postoperative follow-up. CONCLUSION: Limited data have been published on the long-term survival of corneal grafts after intraocular surgery, especially for extremely {\textquoteright}mature{\textquoteright} corneal transplants. This case series demonstrates that with appropriate preoperative, intraoperative and postoperative measures, successful phacoemulsification can be performed in these cases with excellent long-term results.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316435},
	author = {Franco, Jovany Jeomar and Reyes Luis, Jose Luis and Rahim, Salma and Greenstein, Stephen and Pineda, Roberto}
}
@article {1532370,
	title = {Granulomatosis with polyangiitis presenting as recurrent, multifocal orbital myositis},
	journal = {Orbit},
	volume = {40},
	number = {6},
	year = {2021},
	month = {2021 Dec},
	pages = {529-531},
	abstract = {A 43-year-old woman was referred with a 10\&nbsp;month history of persistent pain in the left orbit. Two years prior, she experienced similar pain in the right orbit. Magnetic resonance imaging (MRI) at the time revealed an enlarged right medial rectus muscle. She was diagnosed with idiopathic orbital myositis and was successfully treated with oral corticosteroids. A year later, she developed symptoms in the left orbit with similar imaging findings. For ten months, she remained on high dose corticosteroids for presumed left medial rectus myositis before presenting to our service. Computed tomography (CT) imaging after corticosteroid taper revealed enlarged left medial rectus and left lateral rectus muscles. Orbital biopsy established a diagnosis of granulomatosis with polyangiitis (GPA), for which she was successfully treated with rituximab. This case underscores the importance of not only proceeding with biopsy in atypical cases of orbital myositis but to also taper steroids prior to biopsy.},
	keywords = {Adult, Female, Granulomatosis with Polyangiitis, Humans, Magnetic Resonance Imaging, Oculomotor Muscles, Orbit, Orbital Myositis},
	issn = {1744-5108},
	doi = {10.1080/01676830.2020.1817949},
	author = {Franco, Jovany and Lee, Nahyoung Grace}
}
@article {1667703,
	title = {An ultralow-cost portable centrifuge from discarded materials for medical applications},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Feb 22},
	pages = {3081},
	abstract = {Reliable centrifugation for medical applications has historically required access to expensive, bulky, and electricity-dependent commercial devices, which are generally unavailable in resource-poor settings. Although several portable, low-cost, non-electric centrifuges have been described, these solutions have predominately been designed for diagnostic applications requiring sedimentation of relatively small volumes. Moreover, construction of these devices frequently requires access to specialized materials and tools that are often unavailable in underserved areas. Herein, we describe the design, assembly, and experimental validation of the CentREUSE-an ultralow-cost, portable, discarded material-based, human-powered centrifuge for use in therapeutic applications. The CentREUSE demonstrated a mean centrifugal force of 10.5 relative centrifugal force (RCF) {\textpm} 1.3. Sedimentation of 1.0\&nbsp;mL triamcinolone acetonide suspension for intravitreal use after 3\&nbsp;min of CentREUSE centrifugation was comparable to that achieved after 12\&nbsp;h of gravity-mediated sedimentation (0.41\&nbsp;mL {\textpm} 0.04 vs. 0.38\&nbsp;mL {\textpm} 0.03, p = 0.14). Sediment compactness after 5\&nbsp;min and 10\&nbsp;min of CentREUSE centrifugation was similar to that observed after centrifugation with a commercial device for 5\&nbsp;min at 10 RCF (0.31\&nbsp;mL {\textpm} 0.02 vs. 0.32\&nbsp;mL {\textpm} 0.03, p = 0.20) and 50 RCF (0.20\&nbsp;mL {\textpm} 0.02 vs. 0.19\&nbsp;mL {\textpm} 0.01, p = 0.15), respectively. Templates and instructions for construction of the CentREUSE are included as part of this open-source publication.},
	keywords = {Centrifugation, Humans, Triamcinolone Acetonide},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-30327-2},
	author = {Franco, Jovany J and Nagata, Tatsuo and Okamoto, Takayuki and Mukai, Shizuo}
}
@article {1732581,
	title = {Conforming to the anatomy and not the standard: A technique of eccentric capsulorrhexis and intraocular lens haptic amputation for eyes with iris coloboma},
	journal = {Eur J Ophthalmol},
	volume = {33},
	number = {4},
	year = {2023},
	month = {2023 Jul},
	pages = {1740-1745},
	abstract = {PURPOSE: To describe a novel technique for cataract surgery in patients with iris coloboma. METHODS: The technique involves 1) creation of an inferiorly displaced capsulorrhexis and 2) amputation of one intraocular lens (IOL) haptic, thus allowing for controlled IOL decentration in the direction of an inferior iris defect. RESULTS: We report favorable outcomes in two eyes (one patient) where eccentric capsulorrhexis and haptic amputation were employed during one-piece IOL repositioning in one eye and cataract surgery with three-piece IOL implantation in the contralateral eye. CONCLUSION: In coloboma patients who are asymptomatic from their iris defect and do not have a cosmetic desire for repair, eccentric capsulorrhexis and IOL haptic amputation is a viable surgical option that allows for the preservation of a clear visual axis without the need for iris repair.},
	keywords = {Capsulorhexis, Cataract, Coloboma, Haptic Technology, Humans, Iris, Iris Diseases, Lens Implantation, Intraocular, Lenses, Intraocular},
	issn = {1724-6016},
	doi = {10.1177/11206721231155208},
	author = {Franco, Jovany J and Pineda, Roberto}
}
@article {1709801,
	title = {Prevalence of cerebrotendinous xanthomatosis among patients diagnosed with early-onset idiopathic bilateral cataracts: final analysis},
	journal = {J AAPOS},
	year = {2023},
	month = {2023 Jun 14},
	abstract = {Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC >= 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9\% in enrolled patients, and 15.4\% in patients who met the criteria for genetic testing.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.04.013},
	author = {Freedman, Sharon F and Del Monte, Monte A and Diva, Ulysses and Donahue, Sean P and Drack, Arlene V and Dutta, Rana and Fung, Simon S M and Imperiale, Michael and Jordan, Catherine O and Lenhart, Phoebe D and Lim, Maria E and McCourt, Emily A and Nihalani, Bharti R and Sabahi, Tarlan and Stahl, Erin D and Miraldi Utz, Virginia A and Wilson, M Edward and Yen, Kimberly G and VanderVeen, Deborah K}
}
@article {1559550,
	title = {Glaucoma-Related Adverse Events at 10 Years in the Infant Aphakia Treatment Study: A Secondary Analysis of a Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {2},
	year = {2021},
	month = {2021 Feb 01},
	pages = {165-173},
	abstract = {Importance: Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking. Objective: To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment. Design, Setting, and Participants: Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019. Interventions: Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Main Outcomes and Measures: Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs. Results: In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9\% (95\% CI, 5\%-16\%) at 1 year, to 17\% (95\% CI, 11\%-25\%) at 5 years, to 22\% (95\% CI, 16\%-31\%) at 10 years. The risk of glaucoma plus  glaucoma suspect diagnosis after cataract removal rose from 12\% (95\% CI, 7\%-20\%) at 1 year, to 31\% (95\% CI, 24\%-41\%) at 5 years, to 40\% (95\% CI, 32\%-50\%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years. Conclusions and Relevance: Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years. Trial Registration: ClinicalTrials.gov Identifier: NCT00212134.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.5664},
	author = {Freedman, Sharon F and Beck, Allen D and Nizam, Azhar and VanderVeen, Deborah K and Plager, David A and Morrison, David G and Drews-Botsch, Carolyn D and Lambert, Scott R and Infant Aphakia Treatment Study Group}
}
@article {1655733,
	title = {Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity: Reactivations, Additional Treatments, and 12-Month Outcomes},
	journal = {Ophthalmology},
	volume = {129},
	number = {10},
	year = {2022},
	month = {2022 10},
	pages = {1120-1128},
	abstract = {PURPOSE: Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: One hundred twenty prematurely born infants with type 1 ROP. METHODS: A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. MAIN OUTCOME MEASURES: Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. RESULTS: Sixty-two of 113 study eyes (55\%) and 55 of 98 fellow eyes (56\%) received additional treatment. Of the study eyes, 31 (27\%) received additional ROP treatment, and 31 (27\%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3\% and 5\%, respectively), optic atrophy was noted in 10\%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29\% of infants. CONCLUSIONS: Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Gestational Age, Humans, Infant, Infant, Newborn, Intravitreal Injections, Laser Coagulation, Retinopathy of Prematurity, Retrospective Studies},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.05.019},
	author = {Freedman, Sharon F and Hercinovic, Amra and Wallace, David K and Kraker, Raymond T and Li, Zhuokai and Bhatt, Amit R and Boente, Charline S and Crouch, Eric R and Hubbard, G Baker and Rogers, David L and Vanderveen, Deborah and Yang, Michael B and Cheung, Nathan L and Cotter, Susan A and Holmes, Jonathan M and Pediatric Eye Disease Investigator Group}
}
@article {1522715,
	title = {Sentinel Lymph Node Biopsy for Eyelid and Conjunctival Malignancy: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {127},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {1757-1765},
	abstract = {PURPOSE: To determine the efficacy and safety of sentinel lymph node biopsy (SLNB) in the management of eyelid and conjunctival malignancy. METHODS: A literature search was performed in August 2019 and January 2020 for articles published in English in the PubMed and Cochrane Library databases. This search yielded 151 articles that were reviewed for relevancy, of which 27 were deemed to have met the inclusion criteria for this assessment. The data from these articles were abstracted and the articles were rated for strength of evidence by the panel methodologist. RESULTS: All 27 studies were rated level III, and a total of 197 SLNBs were reported. Diagnoses included conjunctival and eyelid cutaneous melanoma (85 and 42 patients, respectively), sebaceous gland carcinoma (35 patients), squamous cell carcinoma (26 patients), Merkel cell carcinoma (6 patients), pigmented epithelioid melanocytoid tumor (1 patient), mucoepidermoid carcinoma (1 patient), and signet ring carcinoma (1 patient). Tracer was found in regional lymph nodes in 100\% of patients in 21 of 27 articles and in 191 of 197 patients overall. The number of lymph nodes removed ranged from 1 to 16, with most ranging from 1 to 5. Tumor-positive lymph nodes were found in 33 of 197 patients (16.8\%), prompting recommendations for adjuvant treatments. Survival data were reported for 16 of these patients, with follow-up periods ranging from 3 to 36 months (average, 12.7 months). Fourteen of 16 patients received adjuvant treatments. Nine were alive and well, 1 was alive with metastases, and 6 had died of metastatic disease (including 2 patients who declined additional treatment). False-negative SLNB results were reported in 5 articles involving 9 of 197 procedures (4.6\%). Complications were documented in 7 of 27 articles and included transient facial nerve weakness, persistent blue dye staining of the conjunctiva, neck hematoma, and suture abscess. CONCLUSIONS: Sentinel lymph node biopsy is a promising procedure in patients with eyelid and conjunctival malignancy, and it is useful in identifying sentinel lymph nodes. However, at present, insufficient evidence exists showing that SLNB improves patient outcomes and survival. Recognition of microscopic metastatic disease may prove beneficial in staging and guiding adjuvant therapy.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.07.031},
	author = {Freitag, Suzanne K and Aakalu, Vinay K and Tao, Jeremiah P and Wladis, Edward J and Foster, Jill A and Sobel, Rachel K and Yen, Michael T}
}
@article {959396,
	title = {Preoperative imaging should be performed prior to surgery in all cases of acquired nasolacrimal obstruction-Yes},
	journal = {Eye (Lond)},
	volume = {31},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {351-352},
	issn = {1476-5454},
	doi = {10.1038/eye.2016.237},
	author = {Freitag, S K and Roos, J C P}
}
@article {1354335,
	title = {Retrospective review of eyelash number in patients who have undergone full-thickness eyelid resection},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {30},
	number = {1},
	year = {2014},
	month = {2014 Jan-Feb},
	pages = {1-6},
	abstract = {PURPOSE: The purpose of this study was to determine whether a localized full-thickness eyelid excision results in a proportional decrease in the total number of eyelashes or whether a full complement of visible lashes persists, thus suggesting a compensatory increase in the anagen/telogen ratio among the remaining follicles. METHODS: A retrospective chart review was performed on 38 patients who underwent full-thickness eyelid resections repaired with primary eyelid closure for either benign or malignant eyelid lesions. Demographic and surgical data were collected, postoperative eyelid photographs were reviewed, and eyelashes were counted. RESULTS: There were 10 upper eyelids and 28 lower eyelids in 10 men and 28 women, with an average age of 57.9 years (range, 14-86 years). The lesion pathology was benign in 21 cases (55\%) and malignant in 17 cases (45\%). The full-thickness defect involved \&lt;25\% of the eyelid in 16 cases (42\%) and \&gt;25\% of the eyelid in 22 cases (58\%). The follow-up period ranged from 50 to 319 days, with an average of 94 days. In contralateral controls, upper eyelids had an average of 72.1 lashes and lower eyelids had an average of 38.2 lashes, and there was no statistical significance between men and women. In lower lids that underwent \&lt;25\% resection, control lids had an average of 37.3 lashes and operative lids had 37.1 lashes. In lower lids that underwent \&gt;25\% resection, control lids had an average of 38.7 lashes and operative lids had 34.2 lashes. This represents an 11.6\% decrease and was statistically significant. In upper eyelids that underwent \&lt;25\% resection and \&gt;25\% resection, control eyelids had an average of 74.9 lashes and 69.3 lashes and operative eyelids had 77.6 lashes and 69.1 lashes, respectively. Finally, lash count was compared by benign versus malignant pathologic diagnosis. In upper eyelids with benign lesions and malignant lesions, control eyelids had an average of 73.8 lashes and 65.3 lashes and operative eyelids had 74.6 lashes and 68.3 lashes, respectively. In lower eyelids with benign pathology and malignant lesions, control eyelids had an average of 34.5 lashes and 41.4 lashes and operative eyelids had 33.8 lashes and 36.8 lashes. This represents an 11.1\% decrease and was statistically significant. CONCLUSIONS: Full-thickness excision of eyelid margin tissue including lashes does not usually affect postoperative lash numbers. Because the total number of follicles is reduced, the percentage of lashes in the anagen versus the resting or telogen phase apparently increases compared with the preoperative state. This eyelash study contributes to the growing body of literature on the poorly understood topic of hair follicle cycle regulation.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Blepharoplasty, Eyelashes, Eyelids, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e3182a650bb},
	author = {Freitag, Suzanne K and Lee, Henry and Lee, Nahyoung Grace and Johnstone, Murray A and Sires, Bryan S}
}
@article {1580476,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {128},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {e29-e30},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.01.013},
	author = {Freitag, Suzanne K and Yen, Michael T}
}
@article {1478330,
	title = {A Nomenclature to Describe the Sequence of Visual Field Defects in Progressive Thyroid Eye Disease-Compressive Optic Neuropathy (An American Ophthalmological Society Thesis)},
	journal = {Am J Ophthalmol},
	volume = {213},
	year = {2020},
	month = {2020 May},
	pages = {293-305},
	abstract = {PURPOSE: To create a novel nomenclature to characterize the longitudinal sequence of visual field (VF) defects in patients with progression of thyroid eye disease-compressive optic neuropathy (TED-CON). METHODS: A retrospective review of records from 1 institution identified patients with progressive Humphrey VF defects secondary to TED-CON. The VF defects were analyzed by 2 independent reviewers and classified into 1 of 10 categories, divided into 3 stages that reflect the observed progression pattern, plus a miscellaneous category (stage X). Stage 1 VF defects are the earliest detectable and involve the inferior visual field with 3 levels of severity. Stage 2 VF defects include 2 distinguishable levels of severity and occur as the inferior defects advance above the horizontal midline to involve the superior VF. Stage 3 involves progression of stage 2 VF defects to complete loss of inferior and superior hemifields. RESULTS: Of 234 VFs in 37 eyes of 23 subjects, inferior defects were most common, including stage 1a (small inferior paracentral defect) in 22 of 234 VFs (9.4\%), stage 1b (large inferior paracentral defect) in 112 of 234 VFs (47.9\%), and stage 1c (inferior altitudinal defect) in 11 of 234 VFs (4.7\%). Stage 2a (inferior altitudinal with superior advancement above the horizontal meridian) occurred in 41 of 234 VFs (17.5\%), stage 2b (inferior altitudinal with superior arcuate) occurred in 6 of 234 VFs (2.6\%), and stage 3 (total loss) occurred in 5 of 234 VFs (2.1\%). The longitudinal sequence of VF defects from the 37 eyes of 23 patients was analyzed. Thirty-one of 37 eyes (83.8\%) demonstrated a predictable progression pattern from least to more severe: stage 1a, stage 1b, stage 1c, stage 2a, stage 2b, and stage 3. A reverse order of VF defect progression was noted in 15 eyes with improving TED-CON. A minority of progression patterns (16.2\%) originated from stage X (central/paracentral, enlarged blind spot, and scatter). CONCLUSIONS: Humphrey VF defects resulting from TED-CON are most often inferior, often have a predictable pattern of progression, and can be categorized into a novel descriptive nomenclature system. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.12.005},
	author = {Freitag, Suzanne K and Tanking, Thidarat}
}
@article {1748521,
	title = {Use of Mitomycin C in Dacryocystorhinostomy: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {130},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1212-1220},
	abstract = {PURPOSE: To review the literature on the adjuvant use of mitomycin C (MMC) during dacryocystorhinostomy (DCR) in adults with primary nasolacrimal duct obstructions (NLDOs) to determine the efficacy in improving functional and anatomic outcomes with an acceptable level of risk. METHODS: A literature search conducted in November 2020 and updated in November 2022 yielded 137 articles. Twenty-four articles met the inclusion criteria and were rated for level of evidence by the panel methodologist. Inclusion criteria required controlled studies on the effect of MMC on outcomes of external, endoscopic endonasal, or diode laser-assisted transcanalicular DCR in adults with primary acquired nasolacrimal obstruction with 6 months minimum follow-up and at least 10 participants. RESULTS: Six of the 24 articles were rated level I evidence, 15 level II , and 3 level III. In primary external DCR, MMC significantly improved functional outcomes in 3 of 9 series. In primary endoscopic endonasal DCR, MMC significantly improved functional outcomes in 1 of 9 series. In revision endoscopic endonasal DCR, MMC significantly improved functional success in 1 of 3 series. The use of MMC did not improve outcomes statistically in any diode laser-assisted transcanalicular DCR studies. Concentrations of MMC ranged from 0.05 to 1 mg/ml, with 0.2 mg/ml used most frequently in 12 series, with duration of application ranging from 2 to 30 minutes. Ostium size was significantly larger in MMC groups than in control groups at 6 months after surgery in 4 of 5 reporting studies. However, these larger ostia did not confer higher functional success rates. Reporting of adverse events related to MMC were rare, with delayed cutaneous wound healing reported in 1 of 750 patients. CONCLUSIONS: Intraoperative use of MMC in external and endoscopic endonasal DCR has been shown to improve functional and anatomic outcomes compared with controls in some series, but there is no agreement on the recommended concentration or application time for MMC in DCR. The data support that MMC use can result in a larger ostium size, decreased granulation tissue formation, and a decreased number of postoperative nasal debridements compared with controls, but this does not translate into improved functional success. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.06.024},
	author = {Freitag, Suzanne K and Aakalu, Vinay K and Foster, Jill A and McCulley, Timothy J and Tao, Jeremiah P and Vagefi, M Reza and Yen, Michael T and Kim, Stephen J and Wladis, Edward J}
}
@article {1263326,
	title = {Re: Duarte et al.: Lacrimal gland involvement in blepharophimosis-ptosis-epicanthus inversus syndrome (Ophthalmology. 2017;124:399-406)},
	journal = {Ophthalmology},
	volume = {124},
	number = {11},
	year = {2017},
	month = {2017 Nov},
	pages = {e83},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.06.014},
	author = {Freitag, Suzanne K}
}
@article {1642033,
	title = {Acute Angle-Closure Attacks Are Uncommon in Primary Angle-Closure Suspects after Pharmacologic Mydriasis: The Zhongshan Angle-Closure Prevention Trial},
	journal = {Ophthalmol Glaucoma},
	volume = {5},
	number = {6},
	year = {2022},
	month = {2022 Nov-Dec},
	pages = {581-586},
	abstract = {PURPOSE: Angle-closure glaucoma is a major cause of blindness worldwide that carries an excessive risk of severe, bilateral visual impairment. A common concern among clinicians is the precipitation of acute angle-closure (AAC) attacks because of mydriasis. We evaluated the risk of AAC after pharmacologic dilation in Chinese individuals classified as having bilateral primary angle-closure suspects (PACSs). DESIGN: Randomized, interventional, controlled trial. PARTICIPANTS: A total of 889 patients with bilateral PACSs, aged between 50 and 70 years, were identified through community screening in Guangzhou, China, and enrolled in the study. METHODS: In the Zhongshan Angle-Closure Prevention Trial, bilateral PACSs were treated with laser peripheral iridotomy (LPI) in 1 randomly selected eye, with the fellow eye serving as an untreated control. Over 72 months of follow-up, the participants had their pupils pharmacologically dilated 6 times with 5\% phenylephrine and 0.5\% tropicamide. MAIN OUTCOME MEASURES: Incidence and risk of post-mydriasis AAC in LPI-treated and untreated, control eyes classified as PACSs. RESULTS: One bilateral AAC attack occurred after mydriasis at the 2-week post-LPI visit. No other AAC events occurred in the LPI-treated eyes. In the untreated eyes, 4 additional attacks occurred: 2 occurred after dilation (1 at 54 months and 1 at 72 months of follow-up) and 2 occurred spontaneously. The risk of post-mydriasis AAC in the untreated eyes was 1 attack in 1587 dilations. The risk of spontaneous AAC in the untreated eyes was 0.44 per 1000 eye-years (95\% confidence interval, 0.11-1.77 per 1000 eye-years). CONCLUSIONS: The risk of incident AAC attacks in PACSs was extremely low, even in a higher-risk group that underwent repeated pharmacologic pupillary dilation over 6 years of follow-up. Prophylactic LPI reduced this small but real risk. This trial was registered at ISRCTN.com as ISRCTN45213099.},
	keywords = {Acute Disease, Aged, Glaucoma, Angle-Closure, Humans, Laser Therapy, Middle Aged, Mydriasis, Ophthalmologic Surgical Procedures, Phenylephrine},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.04.003},
	author = {Friedman, David S and Chang, Dolly S and Jiang, Yuzhen and Huang, Shengsong and Kim, Julia A and Munoz, Beatriz and Aung, Tin and He, Mingguang and Foster, Paul J}
}
@article {1445333,
	title = {Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita},
	journal = {Hum Mutat},
	volume = {40},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {2270-2285},
	abstract = {Pathogenic variants in the X-linked gene ZC4H2, which encodes a zinc-finger protein, cause an infrequently described syndromic form of arthrogryposis multiplex congenita (AMC) with central and peripheral nervous system involvement. We present genetic and detailed phenotypic information on 23 newly identified families and simplex cases that include 19 affected females from 18 families and 14 affected males from nine families. Of note, the 15 females with deleterious de novo ZC4H2 variants presented with phenotypes ranging from mild to severe, and their clinical features overlapped with those seen in affected males. By contrast, of the nine carrier females with inherited ZC4H2 missense variants that were deleterious in affected male relatives, four were symptomatic. We also compared clinical phenotypes with previously published cases of both sexes and provide an overview on 48 males and 57 females from 42 families. The spectrum of ZC4H2 defects comprises novel and recurrent mostly inherited missense variants in affected males, and de novo splicing, frameshift, nonsense, and partial ZC4H2 deletions in affected females. Pathogenicity of two newly identified missense variants was further supported by studies in zebrafish. We propose ZC4H2 as a good candidate for early genetic testing of males and females with a clinical suspicion of fetal hypo-/akinesia and/or (neurogenic) AMC.},
	issn = {1098-1004},
	doi = {10.1002/humu.23841},
	author = {Frints, Suzanna G M and Hennig, Friederike and Colombo, Roberto and Jacquemont, Sebastien and Terhal, Paulien and Zimmerman, Holly H and Hunt, David and Mendelsohn, Bryce A and Korda{\ss}, Ulrike and Webster, Richard and Sinnema, Margje and Abdul-Rahman, Omar and Suckow, Vanessa and Fern{\'a}ndez-Ja{\'e}n, Alberto and van Roozendaal, Kees and Stevens, Servi J C and Macville, Merryn V E and Al-Nasiry, Salwan and van Gassen, Koen and Utzig, Norbert and Koudijs, Suzanne M and McGregor, Lesley and Maas, Saskia M and Baralle, Diana and Dixit, Abhijit and Wieacker, Peter and Lee, Marcus and Lee, Arthur S and Engle, Elizabeth C and Houge, Gunnar and Gradek, Gyri A and Douglas, Andrew G L and Longman, Cheryl and Joss, Shelagh and Velasco, Danita and Hennekam, Raoul C and Hirata, Hiromi and Kalscheuer, Vera M}
}
@article {647371,
	title = {A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.},
	journal = {Nat Genet},
	volume = {48},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {134-43},
	abstract = {Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of \&gt;12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P \&lt; 5 {\texttimes} 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 {\texttimes} 10(-10)). Very rare coding variants (frequency \&lt;0.1\%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.},
	issn = {1546-1718},
	doi = {10.1038/ng.3448},
	author = {Fritsche, Lars G and Igl, Wilmar and Bailey, Jessica N Cooke and Grassmann, Felix and Sengupta, Sebanti and Bragg-Gresham, Jennifer L and Burdon, Kathryn P and Hebbring, Scott J and Wen, Cindy and Gorski, Mathias and Kim, Ivana K and Cho, David and Zack, Donald and Souied, Eric and Scholl, Hendrik P N and Bala, Elisa and Lee, Kristine E and Hunter, David J and Sardell, Rebecca J and Mitchell, Paul and Merriam, Joanna E and Cipriani, Valentina and Hoffman, Joshua D and Schick, Tina and Lechanteur, Yara T E and Guymer, Robyn H and Johnson, Matthew P and Jiang, Yingda and Stanton, Chloe M and Buitendijk, Gabri{\"e}lle H S and Zhan, Xiaowei and Kwong, Alan M and Boleda, Alexis and Brooks, Matthew and Gieser, Linn and Ratnapriya, Rinki and Branham, Kari E and Foerster, Johanna R and Heckenlively, John R and Othman, Mohammad I and Vote, Brendan J and Liang, Helena Hai and Souzeau, Emmanuelle and McAllister, Ian L and Isaacs, Timothy and Hall, Janette and Lake, Stewart and Mackey, David A and Constable, Ian J and Craig, Jamie E and Kitchner, Terrie E and Yang, Zhenglin and Su, Zhiguang and Luo, Hongrong and Chen, Daniel and Ouyang, Hong and Flagg, Ken and Lin, Danni and Mao, Guanping and Ferreyra, Henry and Stark, Klaus and von Strachwitz, Claudia N and Wolf, Armin and Brandl, Caroline and Rudolph, Guenther and Olden, Matthias and Morrison, Margaux A and Morgan, Denise J and Schu, Matthew and Ahn, Jeeyun and Silvestri, Giuliana and Tsironi, Evangelia E and Park, Kyu Hyung and Farrer, Lindsay A and Orlin, Anton and Brucker, Alexander and Li, Mingyao and Curcio, Christine A and Mohand-Sa{\"\i}d, Saddek and Sahel, Jos{\'e}-Alain and Audo, Isabelle and Benchaboune, Mustapha and Cree, Angela J and Rennie, Christina A and Goverdhan, Srinivas V and Grunin, Michelle and Hagbi-Levi, Shira and Campochiaro, Peter and Katsanis, Nicholas and Holz, Frank G and Blond, Fr{\'e}d{\'e}ric and Blanch{\'e}, H{\'e}l{\`e}ne and Deleuze, Jean-Fran{\c c}ois and Igo, Robert P and Truitt, Barbara and Peachey, Neal S and Meuer, Stacy M and Myers, Chelsea E and Moore, Emily L and Klein, Ronald and Hauser, Michael A and Postel, Eric A and Courtenay, Monique D and Schwartz, Stephen G and Kovach, Jaclyn L and Scott, William K and Liew, Gerald and Tan, Ava G and Gopinath, Bamini and Merriam, John C and Smith, R Theodore and Khan, Jane C and Shahid, Humma and Moore, Anthony T and McGrath, J Allie and Laux, Rene{\'e} and Brantley, Milam A and Agarwal, Anita and Ersoy, Lebriz and Caramoy, Albert and Langmann, Thomas and Saksens, Nicole T M and de Jong, Eiko K and Hoyng, Carel B and Cain, Melinda S and Richardson, Andrea J and Martin, Tammy M and Blangero, John and Weeks, Daniel E and Dhillon, Bal and van Duijn, Cornelia M and Doheny, Kimberly F and Romm, Jane and Klaver, Caroline C W and Hayward, Caroline and Gorin, Michael B and Klein, Michael L and Baird, Paul N and den Hollander, Anneke I and Fauser, Sascha and Yates, John R W and Allikmets, Rando and Wang, Jie Jin and Schaumberg, Debra A and Klein, Barbara E K and Hagstrom, Stephanie A and Chowers, Itay and Lotery, Andrew J and L{\'e}veillard, Thierry and Zhang, Kang and Brilliant, Murray H and Hewitt, Alex W and Swaroop, Anand and Chew, Emily Y and Pericak-Vance, Margaret A and DeAngelis, Margaret and Stambolian, Dwight and Haines, Jonathan L and Iyengar, Sudha K and Weber, Bernhard H F and Abecasis, Gon{\c c}alo R and Heid, Iris M}
}
@article {1137881,
	title = {Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid Protection Against Choroidal Neovascularization in Mice},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {10},
	year = {2017},
	month = {2017 Aug 01},
	pages = {3862-3870},
	abstract = {Purpose: Neovascular age-related macular degeneration (AMD) is a major cause of legal blindness in the elderly. Diets with omega3-long-chain-polyunsaturated-fatty-acid (ω3-LCPUFA) correlate with a decreased risk of AMD. Dietary ω3-LCPUFA versus ω6-LCPUFA inhibits mouse ocular neovascularization, but the underlying mechanism needs further exploration. The aim of this study was to investigate if adiponectin (APN) mediated ω3-LCPUFA suppression of neovessels in AMD. Methods: The mouse laser-induced choroidal neovascularization (CNV) model was used to mimic some of the inflammatory aspect of AMD. CNV was compared between wild-type (WT) and Apn-/- mice fed either otherwise matched diets with 2\% ω3 or 2\% ω6-LCPUFAs. Vldlr-/- mice were used to mimic some of the metabolic aspects of AMD. Choroid assay ex vivo and human retinal microvascular endothelial cell (HRMEC) proliferation assay in vitro was used to investigate the APN pathway in angiogenesis. Western blot for p-AMPKα/AMPKα and qPCR for Apn, Mmps, and IL-10 were used to define mechanism. Results: ω3-LCPUFA intake suppressed laser-induced CNV in WT mice; suppression was abolished with APN deficiency. ω3-LCPUFA, mediated by APN, decreased mouse Mmps expression. APN deficiency decreased AMPKα phosphorylation in vivo and exacerbated choroid-sprouting ex vivo. APN pathway activation inhibited HRMEC proliferation and decreased Mmps. In Vldlr-/- mice, ω3-LCPUFA increased retinal AdipoR1 and inhibited NV. ω3-LCPUFA decreased IL-10 but did not affect Mmps in Vldlr-/- retinas. Conclusions: APN in part mediated ω3-LCPUFA inhibition of neovascularization in two mouse models of AMD. Modulating the APN pathway in conjunction with a ω3-LCPUFA-enriched-diet may augment the beneficial effects of ω3-LCPUFA in AMD patients.},
	keywords = {Adiponectin, Animals, Biomarkers, Blotting, Western, Cell Proliferation, Choroidal Neovascularization, Disease Models, Animal, Endothelial Cells, Fatty Acids, Omega-3, Macular Degeneration, Matrix Metalloproteinases, Mice, Receptors, Adiponectin},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-21796},
	author = {Fu, Zhongjie and Liegl, Raffael and Wang, Zhongxiao and Gong, Yan and Liu, Chi-Hsiu and Sun, Ye and Cakir, Bertan and Burnim, Samuel B and Meng, Steven S and L{\"o}fqvist, Chatarina and SanGiovanni, John Paul and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {1589761,
	title = {Cellular senescence in pathologic retinal angiogenesis},
	journal = {Trends Endocrinol Metab},
	volume = {32},
	number = {7},
	year = {2021},
	month = {2021 07},
	pages = {415-416},
	abstract = {Pathologic angiogenesis causes blindness in many eye diseases. Crespo-Garcia, Tsuruda, and Dejda et al. employed bioinformatics to characterize cell senescence as a primary factor in the common pathogenesis of retinopathies. They validated their findings using human and mouse retina with proliferative retinopathy. Clearance of senescent cells suppressed neovessel growth.},
	issn = {1879-3061},
	doi = {10.1016/j.tem.2021.03.010},
	author = {Fu, Zhongjie and Smith, Lois E H}
}
@article {961691,
	title = {Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity},
	journal = {Clin Exp Ophthalmol},
	volume = {45},
	number = {5},
	year = {2017},
	month = {2017 Jul},
	pages = {529-538},
	abstract = {BACKGROUND: Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischaemia contributes to its pathogenesis, and lutein protects against ischaemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. METHODS: Mouse pups were exposed to 75\% oxygen for 5\&nbsp;days and returned to room air for another 5\&nbsp;days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. RESULTS: Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in M{\"u}ller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. CONCLUSIONS: Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity because of its role in facilitating the revascularization of normal vasculature.},
	issn = {1442-9071},
	doi = {10.1111/ceo.12908},
	author = {Fu, Zhongjie and Meng, Steven S and Burnim, Samuel B and Smith, Lois E H and Lo, Amy Cy}
}
@article {1016041,
	title = {FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice},
	journal = {Cell Rep},
	volume = {18},
	number = {7},
	year = {2017},
	month = {2017 Feb 14},
	pages = {1606-1613},
	abstract = {Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, we find that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization. FGF21 inhibited tumor necrosis α (TNF-α) expression but did not alter Vegfa expression in neovascular eyes. These data suggest that FGF21 may be a therapeutic target for pathologic vessel growth in patients with neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2017.01.014},
	author = {Fu, Zhongjie and Gong, Yan and Liegl, Raffael and Wang, Zhongxiao and Liu, Chi-Hsiu and Meng, Steven S and Burnim, Samuel B and Saba, Nicholas J and Fredrick, Thomas W and Morss, Peyton C and Hellstrom, Ann and Talukdar, Saswata and Smith, Lois E H}
}
@article {1263331,
	title = {Photoreceptor glucose metabolism determines normal retinal vascular growth},
	journal = {EMBO Mol Med},
	volume = {10},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {76-90},
	abstract = {The neural cells and factors determining normal vascular growth are not well defined even though vision-threatening neovessel growth, a major cause of blindness in retinopathy of prematurity (ROP) (and diabetic retinopathy), is driven by delayed normal vascular growth. We here examined whether hyperglycemia and low adiponectin (APN) levels delayed normal retinal vascularization, driven primarily by dysregulated photoreceptor metabolism. In premature infants, low APN levels correlated with hyperglycemia and delayed retinal vascular formation. Experimentally in a neonatal mouse model of postnatal hyperglycemia modeling early ROP, hyperglycemia caused photoreceptor dysfunction and delayed neurovascular maturation associated with changes in the APN pathway; recombinant mouse APN or APN receptor agonist AdipoRon treatment normalized vascular growth. APN deficiency decreased retinal mitochondrial metabolic enzyme levels particularly in photoreceptors, suppressed retinal vascular development, and decreased photoreceptor platelet-derived growth factor (Pdgfb). APN pathway activation reversed these effects. Blockade of mitochondrial respiration abolished AdipoRon-induced Pdgfb increase in photoreceptors. Photoreceptor knockdown of Pdgfb delayed retinal vascular formation. Stimulation of the APN pathway might prevent hyperglycemia-associated retinal abnormalities and suppress phase I ROP in premature infants.},
	issn = {1757-4684},
	doi = {10.15252/emmm.201707966},
	author = {Fu, Zhongjie and L{\"o}fqvist, Chatarina A and Liegl, Raffael and Wang, Zhongxiao and Sun, Ye and Gong, Yan and Liu, Chi-Hsiu and Meng, Steven S and Burnim, Samuel B and Arellano, Ivana and Chouinard, My T and Duran, Rubi and Poblete, Alexander and Cho, Steve S and Akula, James D and Kinter, Michael and Ley, David and Hansen Pupp, Ingrid and Talukdar, Saswata and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {397796,
	title = {Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin.},
	journal = {Am J Clin Nutr},
	volume = {101},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {879-88},
	abstract = {BACKGROUND: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. OBJECTIVE: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP. DESIGN: Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. RESULTS: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70\% to 10\% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. CONCLUSION: Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.},
	issn = {1938-3207},
	doi = {10.3945/ajcn.114.099291},
	author = {Fu, Zhongjie and Lofqvist, Chatarina A and Shao, Zhuo and Sun, Ye and Joyal, Jean-Sebastien and Hurst, Christian G and Cui, Ricky Z and Evans, Lucy P and Tian, Katherine and SanGiovanni, John Paul and Chen, Jing and Ley, David and Hansen Pupp, Ingrid and Hellstrom, Ann and Smith, Lois E H}
}
@article {1490436,
	title = {Targeting Neurovascular Interaction in Retinal Disorders},
	journal = {Int J Mol Sci},
	volume = {21},
	number = {4},
	year = {2020},
	month = {2020 Feb 22},
	abstract = {The tightly structured neural retina has a unique vascular network comprised of three interconnected plexuses in the inner retina (and choroid for outer retina), which provide oxygen and nutrients to neurons to maintain normal function. Clinical and experimental evidence suggests that neuronal metabolic needs control both normal retinal vascular development and pathological aberrant vascular growth. Particularly, photoreceptors, with the highest density of mitochondria in the body, regulate retinal vascular development by modulating angiogenic and inflammatory factors. Photoreceptor metabolic dysfunction, oxidative stress, and inflammation may cause adaptive but ultimately pathological retinal vascular responses, leading to blindness. Here we focus on the factors involved in neurovascular interactions, which are potential therapeutic targets to decrease energy demand and/or to increase energy production for neovascular retinal disorders.},
	issn = {1422-0067},
	doi = {10.3390/ijms21041503},
	author = {Fu, Zhongjie and Sun, Ye and Cakir, Bertan and Tomita, Yohei and Huang, Shuo and Wang, Zhongxiao and Liu, Chi-Hsiu and Cho, Steve S and Britton, William and Kern, Timothy S and Antonetti, David A and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {705076,
	title = {Review: adiponectin in retinopathy.},
	journal = {Biochim Biophys Acta},
	volume = {1862},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {1392-400},
	abstract = {Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases.},
	issn = {0006-3002},
	doi = {10.1016/j.bbadis.2016.05.002},
	author = {Fu, Zhongjie and Gong, Yan and L{\"o}fqvist, Chatarina and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {1302163,
	title = {Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice},
	journal = {Diabetes},
	volume = {67},
	number = {5},
	year = {2018},
	month = {2018 05},
	pages = {974-985},
	abstract = {Retinal neuronal abnormalities occur before vascular changes in diabetic retinopathy. Accumulating experimental evidence suggests that neurons control vascular pathology in diabetic and other neovascular retinal diseases. Therefore, normalizing neuronal activity in diabetes may prevent vascular pathology. We investigated whether fibroblast growth factor 21 (FGF21) prevented retinal neuronal dysfunction in insulin-deficient diabetic mice. We found that in diabetic neural retina, photoreceptor rather than inner retinal function was most affected and administration of the long-acting FGF21 analog PF-05231023 restored the retinal neuronal functional deficits detected by electroretinography. PF-05231023 administration protected against diabetes-induced disorganization of photoreceptor segments seen in retinal cross section with immunohistochemistry and attenuated the reduction in the thickness of photoreceptor segments measured by optical coherence tomography. PF-05231023, independent of its downstream metabolic modulator adiponectin, reduced inflammatory marker interleukin-1β (IL-1β) mRNA levels. PF-05231023 activated the AKT-nuclear factor erythroid 2-related factor 2 pathway and reduced IL-1β expression in stressed photoreceptors. PF-05231023 administration did not change retinal expression of vascular endothelial growth factor A, suggesting a novel therapeutic approach for the prevention of early diabetic retinopathy by protecting photoreceptor function in diabetes.},
	keywords = {Animals, Antibodies, Monoclonal, Humanized, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Diabetic Retinopathy, Disease Models, Animal, Electroretinography, Fibroblast Growth Factors, Interleukin-1beta, Male, Mice, NF-E2-Related Factor 2, Photoreceptor Cells, Vertebrate, Proto-Oncogene Proteins c-akt, Retinal Neurons, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A},
	issn = {1939-327X},
	doi = {10.2337/db17-0830},
	author = {Fu, Zhongjie and Wang, Zhongxiao and Liu, Chi-Hsiu and Gong, Yan and Cakir, Bertan and Liegl, Raffael and Sun, Ye and Meng, Steven S and Burnim, Samuel B and Arellano, Ivana and Moran, Elizabeth and Duran, Rubi and Poblete, Alexander and Cho, Steve S and Talukdar, Saswata and Akula, James D and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {1661813,
	title = {Thrombospondin 1 missense alleles induce extracellular matrix protein aggregation and TM dysfunction in congenital glaucoma},
	journal = {J Clin Invest},
	volume = {132},
	number = {23},
	year = {2022},
	month = {2022 Dec 01},
	abstract = {Glaucoma is a highly heritable disease that is a leading cause of blindness worldwide. Here, we identified heterozygous thrombospondin 1 (THBS1) missense alleles altering p.Arg1034, a highly evolutionarily conserved amino acid, in 3 unrelated and ethnically diverse families affected by congenital glaucoma, a severe form of glaucoma affecting children. Thbs1R1034C-mutant mice had elevated intraocular pressure (IOP), reduced ocular fluid outflow, and retinal ganglion cell loss. Histology revealed an abundant, abnormal extracellular accumulation of THBS1 with abnormal morphology of juxtacanalicular trabecular meshwork (TM), an ocular tissue critical for aqueous fluid outflow. Functional characterization showed that the THBS1 missense alleles found in affected individuals destabilized the THBS1 C-terminus, causing protein misfolding and extracellular aggregation. Analysis using a range of amino acid substitutions at position R1034 showed that the extent of aggregation was correlated with the change in protein-folding free energy caused by variations in amino acid structure. Extracellular matrix (ECM) proteins, especially fibronectin, which bind to THBS1, also accumulated within THBS1 deposits. These results show that missense variants altering THBS1 p.Arg1034 can cause elevated IOP through a mechanism involving impaired TM fluid outflow in association with accumulation of aggregated THBS1 in the ECM of juxtacanalicular meshwork with altered morphology.},
	keywords = {Alleles, Amino Acids, Animals, Extracellular Matrix Proteins, Glaucoma, Mice, Thrombospondin 1, Trabecular Meshwork},
	issn = {1558-8238},
	doi = {10.1172/JCI156967},
	author = {Fu, Haojie and Siggs, Owen M and Knight, Lachlan Sw and Staffieri, Sandra E and Ruddle, Jonathan B and Birsner, Amy E and Collantes, Edward Ryan and Craig, Jamie E and Wiggs, Janey L and D{\textquoteright}Amato, Robert J}
}
@article {1658657,
	title = {Retinopathy of prematurity: Metabolic risk factors},
	journal = {Elife},
	volume = {11},
	year = {2022},
	month = {2022 Nov 24},
	abstract = {At preterm birth, the retina is incompletely vascularized. Retinopathy of prematurity (ROP) is initiated by the postnatal suppression of physiological retinal vascular development that would normally occur in utero. As the neural retina slowly matures, increasing metabolic demand including in the peripheral avascular retina, leads to signals for compensatory but pathological neovascularization. Currently, only late neovascular ROP is treated. ROP could be prevented by promoting normal vascular growth. Early perinatal metabolic dysregulation is a strong but understudied risk factor for ROP and other long-term sequelae of preterm birth. We will discuss the metabolic and oxygen needs of retina, current treatments, and potential interventions to promote normal vessel growth including control of postnatal hyperglycemia, dyslipidemia and hyperoxia-induced retinal metabolic alterations. Early supplementation of missing nutrients and growth factors and control of supplemental oxygen promotes physiological retinal development. We will discuss the current knowledge gap in retinal metabolism after preterm birth.},
	keywords = {Animals, Disease Models, Animal, Female, Humans, Infant, Newborn, Oxygen, Pregnancy, Premature Birth, Retinal Neovascularization, Retinopathy of Prematurity, Risk Factors},
	issn = {2050-084X},
	doi = {10.7554/eLife.80550},
	author = {Fu, Zhongjie and Nilsson, Anders K and Hellstrom, Ann and Smith, Lois E H}
}
@article {1677826,
	title = {FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP},
	journal = {Angiogenesis},
	volume = {26},
	number = {3},
	year = {2023},
	month = {2023 Aug},
	pages = {409-421},
	abstract = {Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4\&nbsp;weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).},
	keywords = {Animals, Humans, Hyperglycemia, Infant, Newborn, Infant, Premature, Lipids, Mice, Retinopathy of Prematurity},
	issn = {1573-7209},
	doi = {10.1007/s10456-023-09872-x},
	author = {Fu, Zhongjie and Lundgren, Pia and Pivodic, Aldina and Yagi, Hitomi and Harman, Jarrod C and Yang, Jay and Ko, Minji and Neilsen, Katherine and Talukdar, Saswata and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {1466915,
	title = {Dyslipidemia in retinal metabolic disorders},
	journal = {EMBO Mol Med},
	volume = {11},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {e10473},
	abstract = {The light-sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid-rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.},
	issn = {1757-4684},
	doi = {10.15252/emmm.201910473},
	author = {Fu, Zhongjie and Chen, Chuck T and Cagnone, Gael and Heckel, Emilie and Sun, Ye and Cakir, Bertan and Tomita, Yohei and Huang, Shuo and Li, Qian and Britton, William and Cho, Steve S and Kern, Timothy S and Hellstr{\"o}m, Ann and Joyal, Jean-S{\'e}bastien and Smith, Lois E H}
}
@article {469036,
	title = {Embryonic Origin of Postnatal Neural Stem Cells.},
	journal = {Cell},
	volume = {161},
	number = {7},
	year = {2015},
	month = {2015 Jun 18},
	pages = {1644-55},
	abstract = {Adult neural stem/progenitor (B1) cells within the walls of the lateral ventricles generate different types of neurons for the olfactory bulb (OB). The location of B1 cells determines the types of OB neurons they generate. Here we show that the majority of mouse B1 cell precursors are produced between embryonic days (E) 13.5 and 15.5 and remain largely quiescent until they become reactivated postnatally. Using a retroviral library carrying over 100,000 genetic tags, we found that B1 cells share a common progenitor with embryonic cells of the cortex, striatum, and septum, but this lineage relationship is lost before E15.5. The regional specification of B1 cells is evident as early as E11.5 and is spatially linked to the production of neurons that populate different areas of the forebrain. This study reveals an early embryonic regional specification of postnatal neural stem cells and the lineage relationship between them and embryonic progenitor cells.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2015.05.041},
	author = {Fuentealba, Luis C and Rompani, Santiago B and Parraguez, Jose I and Obernier, Kirsten and Romero, Ricardo and Cepko, Constance L and Alvarez-Buylla, Arturo}
}
@article {1504077,
	title = {Inflammatory manifestations in patients with Shwachman-Diamond syndrome: A novel phenotype},
	journal = {Am J Med Genet A},
	volume = {182},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {1754-1760},
	abstract = {Shwachman-Diamond syndrome (SDS) is an autosomal recessive multisystem disorder characterized by exocrine pancreatic dysfunction, bone marrow failure, and leukemia predisposition. Approximately 90\% of cases are due to biallelic mutations in the Shwachman-Bodian-Diamond (SBDS) gene. Additional phenotypic features variably associated with SDS include skeletal, neurologic, hepatic, cardiac, endocrine, and dental abnormalities. We report five subjects with SDS who developed a range of inflammatory manifestations. Three patients developed inflammatory eye conditions. Single cases of juvenile idiopathic arthritis, chronic recurrent multifocal osteomyelitis, and scleroderma were also noted. Clinical presentation and treatment responses are described. Proteomic analysis revealed increased inflammatory signatures in SDS subjects as compared to controls. Treatment of inflammatory manifestations in patients with SDS may be complicated by potential myelosuppressive toxicities of anti-rheumatic medications. Further research is needed to better understand the potential link between inflammatory disorders and SDS to inform effective treatment strategies.},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.61593},
	author = {Furutani, Elissa and Shah, Ankoor S and Zhao, Yongdong and Andorsky, David and Dedeoglu, Fatma and Geddis, Amy and Zhou, Yu and Libermann, Towia A and Myers, Kasiani C and Shimamura, Akiko}
}
@article {397801,
	title = {Disruption of DNA-methylation-dependent long gene repression in Rett syndrome.},
	journal = {Nature},
	year = {2015},
	month = {2015 Mar 11},
	abstract = {Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that has been proposed to function as a transcriptional repressor, but despite numerous mouse studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 protein regulates transcription. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain.},
	issn = {1476-4687},
	doi = {10.1038/nature14319},
	author = {Gabel, Harrison W and Kinde, Benyam and Stroud, Hume and Gilbert, Caitlin S and Harmin, David A and Kastan, Nathaniel R and Hemberg, Martin and Ebert, Daniel H and Greenberg, Michael E}
}
@article {1452963,
	title = {Adaptation to Adversity: the Intermingling of Stress Tolerance and Pathogenesis in Enterococci},
	journal = {Microbiol Mol Biol Rev},
	volume = {83},
	number = {3},
	year = {2019},
	month = {2019 Aug 21},
	abstract = {SUMMARY is a diverse and rugged genus colonizing the gastrointestinal tract of humans and numerous hosts across the animal kingdom. Enterococci are also a leading cause of multidrug-resistant hospital-acquired infections. In each of these settings, enterococci must contend with changing biophysical landscapes and innate immune responses in order to successfully colonize and transit between hosts. Therefore, it appears that the intrinsic durability that evolved to make enterococci optimally competitive in the host gastrointestinal tract also ideally positioned them to persist in hospitals, despite disinfection protocols, and acquire new antibiotic resistances from other microbes. Here, we discuss the molecular mechanisms and regulation employed by enterococci to tolerate diverse stressors and highlight the role of stress tolerance in the biology of this medically relevant genus.},
	issn = {1098-5557},
	doi = {10.1128/MMBR.00008-19},
	author = {Gaca, Anthony O and Lemos, Jos{\'e} A}
}
@article {694751,
	title = {A lysin to kill.},
	journal = {Elife},
	volume = {5},
	year = {2016},
	month = {2016},
	abstract = {An enzyme produced by a bacteriophage can enter human cells and kill intracellular Streptococcus pyogenes.},
	issn = {2050-084X},
	doi = {10.7554/eLife.16111},
	author = {Gaca, Anthony O and Gilmore, Michael S}
}
@article {1709731,
	title = {Lotilaner Ophthalmic Solution 0.25\% for Demodex Blepharitis: Randomized, Vehicle-Controlled, Multicenter, Phase 3 Trial (Saturn-2)},
	journal = {Ophthalmology},
	volume = {130},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {1015-1023},
	abstract = {PURPOSE: To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25\% compared with vehicle for the treatment of Demodex blepharitis. DESIGN: Prospective, randomized, double-masked, vehicle-controlled, multicenter, phase 3 clinical trial. PARTICIPANTS: Four hundred twelve patients with Demodex blepharitis were assigned randomly in a 1:1 ratio to receive either lotilaner ophthalmic solution 0.25\% (study group) or vehicle without lotilaner (control group). METHODS: Patients with Demodex blepharitis treated at 21 United States clinical sites were assigned either to the study group (n\&nbsp;= 203) to receive lotilaner ophthalmic solution 0.25\% or to the control group (n\&nbsp;= 209) to receive vehicle without lotilaner bilaterally twice daily for 6 weeks. Collarettes and erythema were graded for each eyelid at screening and at all visits after baseline. At screening and on days 15, 22, and 43, 4 or more eyelashes were epilated from each eye, and the number of Demodex mites present on the lashes was counted with a microscope. Mite density was calculated as the number of mites per lash. MAIN OUTCOME MEASURES: Outcome measures included collarette cure (collarette grade 0), clinically meaningful collarette reduction to 10 collarettes or fewer (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes as well as erythema), compliance with the drop regimen, drop comfort, and adverse events. RESULTS: At day 43, the study group achieved a statistically significant (P \&lt; 0.0001) higher proportion of patients with collarette cure (56.0\% vs. 12.5\%), clinically meaningful collarette reduction to 10 collarettes or fewer (89.1\% vs. 33.0\%), mite eradication (51.8\% vs. 14.6\%), erythema cure (31.1\% vs. 9.0\%), and composite cure (19.2\% vs. 4.0\%) than the control group. High compliance with the drop regimen (mean {\textpm} standard deviation, 98.7 {\textpm} 5.3\%) in the study group was observed, and 90.7\% of patients found the drops to be neutral to very comfortable. CONCLUSIONS: Twice-daily treatment with lotilaner ophthalmic solution 0.25\% for 6 weeks generally was safe and well tolerated and met the primary end point and all secondary end points for the treatment of Demodex blepharitis compared with vehicle control. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Animals, Blepharitis, Erythema, Eye Infections, Parasitic, Eyelashes, Humans, Mite Infestations, Mites, Ophthalmic Solutions, Prospective Studies},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.05.030},
	author = {Gaddie, Ian Benjamin and Donnenfeld, Eric D and Karpecki, Paul and Vollmer, Patrick and Berdy, Gregg J and Peterson, Jared D and Simmons, Blake and Edell, Aim{\'e}e R P and Whitson, William E and Ciolino, Joseph B and Baba, Stephanie N and Holdbrook, Mark and Trevejo, Jos{\'e} and Meyer, John and Yeu, Elizabeth and Saturn-2 Study Group}
}
@article {1817246,
	title = {New forceps free injection technique for delivering descemet membrane endothelial keratoplasty preloaded endothelium-in grafts},
	journal = {Eur J Ophthalmol},
	volume = {34},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {287-291},
	abstract = {PURPOSE: To describe a new method for delivering DMEK grafts into the recipient{\textquoteright}s eye with endothelium inward configuration using a no-forceps injection technique.

METHODS: We retrospectively review 11 patients that underwent DMEK surgery at our institution using a no-forceps injection technique. The graft was preloaded into an intraocular lens (IOL) cartridge and connected to an anterior chamber maintainer (ACM). A 5 ml non luer lock syringe was inserted into the other end of the ACM to create a one-flow system. The cartridge was inserted into the posterior end of an injector, and the graft was successfully delivered into the recipient{\textquoteright}s eye.

RESULT: Twelve eyes of 11 patients were included. Mean follow-up was 9.16 {\textpm} 1.3 months. At baseline, mean best corrected visual acuity (BCVA) was 0.76 {\textpm} 0.13 logMAr and mean endothelial cell density (ECD) was 2619.00 {\textpm} 115.89 cells/mm2. At follow-up, BCVA significantly improved to 0.22 {\textpm} 0.05 logMAR (p = 0.003). Although we observed a significant reduction in ECD at follow-up (1688 {\textpm} 182.20, p = 0.002), our patients lost only 35.69 {\textpm} 6.36\% of endothelial cells.

CONCLUSION: Our technique can help surgeons safely deliver an endothelium-in graft into the recipient{\textquoteright}s eye. The method doesn{\textquoteright}t require the use of a forceps, minimizing the risk of endothelial cell loss or graft damage.},
	keywords = {Cell Count, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelial Cells, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies, Visual Acuity},
	issn = {1724-6016},
	doi = {10.1177/11206721231208998},
	author = {Gadhvi, Kunal A and Pagano, Luca and Wallace, Alexander and Posarelli, Matteo and Parekh, Mohit and Romano, Vito}
}
@article {1782236,
	title = {Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network},
	journal = {Ophthalmol Ther},
	volume = {13},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {127-147},
	abstract = {INTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts.

METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering >= 50\% of the survey.

RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9\%), adequate (15.6\%), sufficient (16.9\%), or poor (63.6\%). When asked about the first mU gene they thought of, 60.4\% mentioned NOD2, 3.9\% mentioned NLRP3 or MEFV, and 49.4\% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6\% to 55.8\% and were higher for ophthalmologists working in multidisciplinary teams (p \&lt; 0.01). Genetic testing was ordered for suspected mU by 41.6\% of physicians. The availability of molecular techniques did not significantly differ based on geography (p \&gt; 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p \&lt; 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs~prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p \&lt; 0.01) and interleukin-6 (p \&lt; 0.01) inhibitors.

CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.},
	issn = {2193-8245},
	doi = {10.1007/s40123-023-00839-1},
	author = {Gaggiano, Carla and Gupta, Vishali and Agrawal, Rupesh and De Smet, Marc D and Frediani, Bruno and Tosi, Gian Marco and Paroli, Maria Pia and Sridharan, Sudharshan and Pavesio, Carlos E and Pleyer, Uwe and Denisova, Ekaterina V and Babu, Kalpana and de-la-Torre, Alejandra and Yang, Peizeng and Davis, Janet L and Cunningham, Emmett T and Carre{\~n}o, Ester and Goldstein, Debra and Fonollosa, Alex and Cantarini, Luca and Sobrin, Lucia and Fabiani, Claudia}
}
@article {1528398,
	title = {Surgical interventions for primary congenital glaucoma},
	journal = {Cochrane Database Syst Rev},
	volume = {8},
	year = {2020},
	month = {2020 Aug 25},
	pages = {CD008213},
	abstract = {BACKGROUND: Primary congenital glaucoma (PCG) is an optic neuropathy with high intraocular pressure (IOP) that manifests within the first few years of a child{\textquoteright}s life and is not associated with other systemic or ocular abnormalities. PCG results in considerable morbidity even in high-income countries. OBJECTIVES: To compare the effectiveness and safety of different surgical techniques for PCG. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2020, Issue 4); Ovid MEDLINE; Embase.com; PubMed; metaRegister of Controlled Trials (mRCT) (last searched 23 June 2014); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 27 April 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs comparing different surgical interventions in children under five years of age with PCG. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 16 trials (13 RCTs and three quasi-RCTs) with 587 eyes in 446 children. Eleven (69\%) trials were conducted in Egypt and the Middle East, three in India, and two in the USA. All included trials involved children younger than five years of age, with follow-up ranging from six to 80 months. The interventions compared varied across trials. Three trials (on 68 children) compared combined trabeculotomy and trabeculectomy (CTT) with trabeculotomy. Meta-analysis of these trials suggests there may be little to no evidence of a difference between groups in mean IOP (mean difference (MD) 0.27 mmHg, 95\% confidence interval (CI) -0.74 to 1.29; 88 eyes; 2 studies) and surgical success (risk ratio (RR) 1.01, 95\% CI 0.90 to 1.14; 102 eyes; 3 studies) at one year postoperatively. We assessed the certainty of evidence as very low for these outcomes, downgrading for risk of bias (-1) and imprecision (-2). Hyphema was the most common adverse outcome in both groups (no meta-analysis due to considerable heterogeneity; I = 83\%). Two trials (on 39 children) compared viscotrabeculotomy to conventional trabeculotomy. Meta-analysis of 42 eyes suggests there is no evidence of between groups difference in mean IOP (MD -1.64, 95\% CI -5.94 to 2.66) and surgical success (RR 1.11, 95\% CI 0.70 to 1.78) at six months postoperatively. We assessed the certainty of evidence as very low, downgrading for risk of bias and imprecision due to small sample size. Hyphema was the most common adverse outcome (38\% in viscotrabeculotomy and 28\% in conventional trabeculotomy), with no evidence of difference difference (RR 1.33, 95\% CI 0.63 to 2.83). Two trials (on 95 children) compared microcatheter-assisted 360-degree circumferential trabeculotomy to conventional trabeculotomy. Meta-analysis of two trials suggests that mean IOP may be lower in the microcatheter group at six months (MD -2.44, 95\% CI -3.69 to -1.19; 100 eyes) and at 12 months (MD -1.77, 95\% CI -2.92 to -0.63; 99 eyes); and surgical success was more likely to be achieved in the microcatheter group compared to the conventional trabeculotomy group (RR 1.59, 95\% CI 1.14 to 2.21; 60 eyes; 1 trial at 6 months; RR 1.54, 95\% CI 1.20 to 1.97; 99 eyes; 2 trials at 12 months). We assessed the certainty of evidence for these outcomes as moderate due to small sample size. Hyphema was the most common adverse outcome (40\% in the microcatheter group and 17\% in the conventional trabeculotomy group), with greater likelihood of occurring in the microcatheter group (RR 2.25, 95\% CI 1.25 to 4.04); the evidence was of moderate certainty due to small sample size (-1). Of the nine remaining trials, no two trials compared the same two surgical interventions: one trial compared CTT versus CTT with sclerectomy; three trials compared various suturing techniques and adjuvant use including mitomycin C, collagen implant in CTT; one trial compared CTT versus Ahmed valve implant in previously failed surgeries; one trial compared CTT with trabeculectomy; one trial compared trabeculotomy to goniotomy; and two trials compared different types of goniotomy. No trials reported quality of life or economic data. Many of the included trials had limitations in study design, implementation, and reporting, therefore the reliability and applicability of the evidence remains unclear. AUTHORS{\textquoteright} CONCLUSIONS: The evidence suggests that there may be little to no evidence of difference between CTT and routine conventional trabeculotomy, or between viscotrabeculotomy and routine conventional trabeculotomy. A 360-degree circumferential trabeculotomy may show greater surgical success than conventional trabeculotomy. Considering the rarity of the disease, future research would benefit from a multicenter, possibly international trial, involving parents of children with PCG and with a follow-up of at least one year.},
	issn = {1469-493X},
	doi = {10.1002/14651858.CD008213.pub3},
	author = {Gagrani, Meghal and Garg, Itika and Ghate, Deepta}
}
@article {1559567,
	title = {Persistent vasa hyaloidea propria/retinae in familial exudative vitreoretinopathy},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Dec 21},
	abstract = {The vasa hyaloidea propria, a component of the fetal hyaloidal vasculature, is characterized by multiple persistent fetal vasculatures branching into the vitreous. We present a 4-month-old girl with stage 4 familial exudative vitreoretinopathy, with multiple ectopic retinal vessels extending into the vitreous, confirmed with fluorescein angiography, which was consistent with persistent vasa hyaloidea propia/retinae making contact with the retina. The patient underwent vitreoretinal surgery to address the retinal detachment, during which the patent stalks of the persistent vasa hyaloidea propia/retinae were transected.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.11.004},
	author = {Gaier, Eric D and Yonekawa, Yoshihiro}
}
@article {1483604,
	title = {Novel homozygous mutation in an Afghani family with 3-methylglutaconic aciduria type III and optic atrophy},
	journal = {Ophthalmic Genet},
	volume = {40},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {570-573},
	abstract = {: To describe and distinguish clinical phenotypes with the overlapping feature of optic atrophy caused by distinct mutations in the same gene, OPA3. We report 3 affected siblings in a consanguineous family harboring a novel OPA3 mutation causing 3-methylglutaconic aciduria type III with optic atrophy.: Retrospective case series.: Three siblings (2 male, 1 female) among 6 children in a consanguineous Afghani family developed decreased vision from early childhood. Both parents and all extended family members were unaffected. All 3 affected siblings suffered from severe visual impairment ranging from visual acuities of 20/150 to counting fingers. All had spastic lower extremity weakness and ataxia. Two of the three affected siblings also had a history of seizures, and the female sibling had limited cognition with diffuse atrophic changes on brain MRI. Two of the three individuals also had migraine-like headaches. Urine organic acid analysis revealed mildly elevated 3-methylglutaconic acid for the male siblings. Whole exome sequencing and subsequent PCR confirmation revealed a novel variant in OPA3 (intron1, c.142\&nbsp;+\&nbsp;2_142\&nbsp;+\&nbsp;3dupTG), affecting the consensus sequence of the splice site, for which all 3 clinically affected siblings were homozygous.: Mutations in OPA3 can cause optic atrophy in a dominant pattern of inheritance associated with cataract or in a recessive pattern associated with spastic paresis and ataxia. The novel recessive mutation and clinical presentations described herein further support how different mutation types affecting OPA3 can produce distinct clinical phenotypes and underscore the critical and susceptible role of mitochondrial health in optic nerve function.},
	issn = {1744-5094},
	doi = {10.1080/13816810.2019.1711428},
	author = {Gaier, Eric D and Sahai, Inderneel and Wiggs, Janey L and McGeeney, Brian and Hoffman, Jodi and Peeler, Crandall E}
}
@article {931056,
	title = {Peripapillary Capillary Dilation in Leber Hereditary Optic Neuropathy Revealed by Optical Coherence Tomographic Angiography.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {11},
	year = {2016},
	month = {2016 Nov 01},
	pages = {1332-1334},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.3593},
	author = {Gaier, Eric D and Gittinger, John W and Cestari, Dean M and Miller, John B}
}
@article {1645483,
	title = {Sectoral Sparing Associated With a Cilioretinal Artery in Arteritic Anterior Ischemic Optic Neuropathy},
	journal = {J Neuroophthalmol},
	volume = {42},
	number = {2},
	year = {2022},
	month = {2022 06 01},
	pages = {e514-e516},
	abstract = {ABSTRACT: Giant cell arteritis (GCA) is a life-threatening vasculitis occurring in older adults that can cause blindness by ischemia of the choroid, retina, and optic nerve. We report a case of a patient who presented with "occult" GCA with severe anterior ischemic optic neuropathy affecting both optic nerves, delayed choroidal filling, and a concomitant cilioretinal artery occlusion in the left eye. The retinal territory supplied by the affected cilioretinal artery was hypoperfused, yet this retinal territory at least partially corresponded to the only preserved visual field in that eye. The sector of the optic disc corresponding to the emergence of the cilioretinal artery was the only sector spared by pallid edema. This pattern of sectoral sparing associated with a cilioretinal artery has been observed in other patients with GCA and in animal models of posterior ciliary artery occlusion. This case serves as a clear example of an incompletely understood phenomenon in posterior pole circulation in vascular occlusive disease that deserves further study.},
	keywords = {Aged, Animals, Ciliary Arteries, Giant Cell Arteritis, Humans, Optic Neuropathy, Ischemic, Retinal Artery Occlusion, Retinal Vessels},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001418},
	author = {Gaier, Eric D and Rasool, Nailyn and Rizzo, Joseph F}
}
@article {1773536,
	title = {Comments on: Partial Recovery of Amblyopia After Fellow Eye Ischemic Optic Neuropathy: Response},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 Oct 04},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001996},
	author = {Gaier, Eric D and Bear, Mark F}
}
@article {882921,
	title = {The enigma of nonarteritic anterior ischemic optic neuropathy: an update for the comprehensive ophthalmologist.},
	journal = {Curr Opin Ophthalmol},
	year = {2016},
	month = {2016 Aug 31},
	abstract = {PURPOSE OF REVIEW: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic nerve injury, and frequently presents to comprehensive ophthalmologists. We review the typical and atypical clinical features and current literature on various treatment modalities for NAION. RECENT FINDINGS: The epidemiology and clinical presentation of this disease can be variable, making a definitive diagnosis difficult in many cases. In addition, the differential diagnoses for this disorder, although comprising much less prevalent entities, are quite broad and can have substantial systemic implications if these alternatives go unrecognized. NAION has many systemic associations and comorbidities that deserve inquiry when the diagnosis is made. There are currently no widely accepted, evidence-based treatments for NAION. All recommendations made to patients to reduce their risk of sequential eye involvement, including avoidance of potential nocturnal hypotension, erectile dysfunction medication, and treatment of obstructive sleep apnea, have theoretical bases. SUMMARY: NAION is a common cause of acute vision loss in adult and older patients, and thus, comprehensive ophthalmologists need to be able to diagnose and appropriately manage this disorder. We anticipate fruitful results from current and future trials aimed at neuroprotection in the affected eye and prevention of sequential eye involvement.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000318},
	author = {Gaier, Eric D and Torun, Nurhan}
}
@article {591191,
	title = {Atypical Optic Neuritis.},
	journal = {Curr Neurol Neurosci Rep},
	volume = {15},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {76},
	abstract = {Classic demyelinative optic neuritis is associated with multiple sclerosis and typically carries a good prognosis for visual recovery. This disorder is well characterized with respect to its presentation and clinical features by baseline data obtained through the optic neuritis treatment trial and numerous other studies. Atypical optic neuritis entails clinical manifestations that deviate from this classic pattern of features. Clinical signs and symptoms that deviate from the typical presentation should prompt consideration of less common etiologies. Atypical features to consider include lack of pain, simultaneous or near-simultaneous onset, lack of response to or relapse upon tapering from corticosteroids, or optic nerve head or peripapillary hemorrhages. The most important alternative etiologies to consider and the steps towards their respective diagnostic evaluations are suggested for these atypical features.},
	issn = {1534-6293},
	doi = {10.1007/s11910-015-0598-1},
	author = {Gaier, Eric D and Boudreault, Katherine and Rizzo, Joseph F and Falardeau, Julie and Cestari, Dean M}
}
@article {1478329,
	title = {Pediatric Idiopathic Intracranial Hypertension},
	journal = {Semin Neurol},
	volume = {39},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {704-710},
	abstract = {The presentation of idiopathic intracranial hypertension (IIH) in pediatric populations has several important distinctions from that in adults, especially among prepubertal patients, in which there is no apparent association with gender or obesity. Pediatric patients are more likely to be asymptomatic or present with atypical symptoms than their adult counterparts, posing a diagnostic challenge in some cases. It is important to be aware of the ways in which diagnostic criteria for IIH are modified from that of adults. Ideal treatment practices and the natural history of pediatric IIH remain unclear. Acetazolamide is the mainstay of medical treatment, but some patients with significant visual loss may require surgical intervention. Multicenter studies to accrue a large number of cases and future prospective studies will help to better define pediatric IIH and to formulate consensus guidelines for treatment and management of these patients.},
	issn = {1098-9021},
	doi = {10.1055/s-0039-1698743},
	author = {Gaier, Eric D and Heidary, Gena}
}
@article {1470967,
	title = {Poor prognoses of open globe injuries with concomitant orbital fractures},
	journal = {Orbit},
	volume = {39},
	number = {4},
	year = {2020},
	month = {2020 Aug},
	pages = {241-250},
	abstract = {PURPOSE: Orbital trauma, particularly with open globe injury, can have a wide range of visual outcomes, which can be difficult to predict at presentation. Clinical features on presentation may provide insight into visual prognosis. We hypothesized that patients with open globe injuries and concomitant orbital fractures have poorer visual outcomes than patients without orbital fractures. METHODS: We reviewed the charts of 77 patients with isolated open globe injuries (OG) and 76 patients with open globe injuries and concomitant orbital fractures (OGOF). Multivariate regression analysis was performed to assess the relative influence of individual presenting historical and clinical features on visual outcome. RESULTS: OGOF patients were more likely to have sustained blunt trauma than a sharp, penetrating injury compared to OG patients. Ocular wound locations were more posterior and likely to involve multiple zones in OGOF compared to OG patients. Among OGOF patients, orbital floor fractures were the most common and roof fractures were the least common, but the latter was associated with presenting NLP vision and multiple zone involvement. The presence of an orbital fracture independently increased the odds of subsequent evisceration/enucleation (OR: 4.6, 95\% CI 1.3-20.1, =\&nbsp;.0246) and NLP vision (OR: 6.81, 95\% CI 2.42-21.85, =\&nbsp;.0005) when controlling for zone, mechanism of injury, uveal prolapse and demographic variables. CONCLUSIONS: The presence of an orbital fracture independently confers a worse visual and ocular prognosis in patients with open globe injuries. Patients with open globe injuries in this category should be appropriately counseled.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2019.1663881},
	author = {Gaier, Eric D and Tarabishy, Sami and Bayers, Christopher and Wolkow, Natalie and Gardiner, Matthew and Lefebvre, Daniel R and Grob, Seanna}
}
@article {1263336,
	title = {Optical coherence tomographic angiography identifies peripapillary microvascular dilation and focal non-perfusion in giant cell arteritis},
	journal = {Br J Ophthalmol},
	volume = {102},
	number = {8},
	year = {2018},
	month = {2018 Aug},
	pages = {1141-1146},
	abstract = {AIMS: We set out to determine the optical coherence tomographic angiography (OCT-A) characteristics of arteritic anterior ischaemic optic neuropathy (AAION) in the context of giant cell arteritis (GCA). METHODS: This is an observational case series of four patients with AAION secondary to GCA, three with unilateral AAION and one with bilateral AAION. We reviewed the charts, fundus photography, visual fields, fluorescein angiography (FA) and OCT-A images for all patients to identify a unifying theme in a range of AAION clinical severity. Imaging of two healthy control eyes from two patients of similar age to the patients in our series were used for comparison. RESULTS: Superficial peripapillary capillary dilation was seen in eyes with acute AAION. It was also noted in the fellow eyes of two patients. Retinal capillary perfusion defects corresponded to visual field loss. Dense optic disc oedema and cotton-wool spots imparted blockage effects. OCT-A laminar analysis did not highlight the choroidal/choriocapillaris perfusion defects seen on FA in two patients. Follow-up OCT-A was obtained in two patients and revealed progression to superficial peripapillary capillary attenuation that corresponded with visual field loss. CONCLUSIONS: There are acute and chronic vascular changes in AAION that are detectable by OCT-A that correspond with visual function. Though the microvascular changes seen in GCA and AAION are not specific, the nearly ubiquitous findings among preclinical and clinically affected eyes in this series of patients with GCA support OCT-A as a potentially useful adjunctive diagnostic test in the work-up of ambiguous cases of suspected ischaemic optic neuropathy.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2017-310718},
	author = {Gaier, Eric D and Gilbert, Aubrey L and Cestari, Dean M and Miller, John B}
}
@article {1445344,
	title = {Imaging Amblyopia: Insights from Optical Coherence Tomography (OCT)},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 03},
	pages = {1-9},
	abstract = {Amblyopia refers to visual impairment resulting from perturbations in visual experience during visual development, typically secondary to strabismus, uncorrected refractive error, and/or deprivation. Amblyopia has traditionally been considered a cortical disease, but the depth of our understanding of this complex neurodevelopmental condition is limited by our ability to appreciate structural pathophysiology in the visual pathway. Recent advances in Optical Coherence Tomography (OCT) have facilitated numerous studies of the structural changes in the retina and optic nerve, thereby expanding our appreciation for the pathogenesis of this condition. In this review, we summarize findings from studies evaluating retinal, retinal nerve fiber layer, and choroidal thickness changes in patients with amblyopia. Focusing on the largest and most recent studies, we discuss common limitations and confounding variables in these studies. We summarize recent advances in ocular imaging technology and reconcile the findings of early histological reports with those of structural OCT in amblyopia.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620810},
	author = {Gaier, Eric D and Gise, Ryan and Heidary, Gena}
}
@article {1059756,
	title = {Combined Central Retinal Vein Occlusion and Central Retinal Arterial Obstruction with Cilioretinal Artery Sparing},
	journal = {Ophthalmology},
	volume = {124},
	number = {4},
	year = {2017},
	month = {2017 Apr},
	pages = {576},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.10.020},
	author = {Gaier, Eric D and Miller, John B and Loewenstein, John I}
}
@article {1319466,
	title = {Quantitative analysis of optical coherence tomographic angiography (OCT-A) in patients with non-arteritic anterior ischemic optic neuropathy (NAION) corresponds to visual function},
	journal = {PLoS One},
	volume = {13},
	number = {6},
	year = {2018},
	month = {2018},
	pages = {e0199793},
	abstract = {PURPOSE: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of non-glaucomatous optic neuropathy in older adults. Optical coherence tomographic angiography (OCT-A) is an emerging, non-invasive method to study the microvasculature of the posterior pole, including the optic nerve head. The goal of this study was to assess the vascular changes in the optic nerve head and peripapillary area associated with NAION using OCT-A. DESIGN: Retrospective comparative case series. METHODS: We performed OCT-A in 25 eyes (7 acute and 18 non-acute) in 19 patients with NAION. Fellow, unaffected eyes were analyzed for comparison. Patent macro- and microvascular densities were quantified in the papillary and peripapillary regions of unaffected, acutely affected, and non-acutely affected eyes and compared across these groups according to laminar segment and capillary sampling region, and with respect to performance on automated visual field testing. RESULTS: In acutely affected eyes, OCT-A revealed a reduction in the signal from the major retinal vessels and dilation of patent superficial capillaries in the peripapillary area. By contrast, non-acutely affected eyes showed attenuation of patent capillaries. The peripapillary choriocapillaris was obscured by edema in acute cases, but was similar between non-acute and unaffected eyes. The degree of dilation of the superficial microvasculature in the acute phase and attenuation in the non-acute phase each correlated inversely with visual field performance. The region of reduced patent capillary density correlated with the location of visual field defects in 80\% of acute cases and 80\% of non-acute cases. CONCLUSIONS: OCT-A reveals a dynamic shift in the superficial capillary network of the optic nerve head with strong functional correlates in both the acute and non-acute phases of NAION. Further study may validate OCT-A as a useful adjunctive diagnostic tool in the evaluation of ischemic optic neuropathy.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0199793},
	author = {Gaier, Eric D and Wang, Mengyu and Gilbert, Aubrey L and Rizzo, Joseph F and Cestari, Dean M and Miller, John B}
}
@article {1078736,
	title = {Focal Capillary Dropout Associated With Optic Disc Drusen Using Optical Coherence Tomographic Angiography},
	journal = {J Neuroophthalmol},
	volume = {37},
	number = {4},
	year = {2017},
	month = {2017 Dec},
	pages = {405-410},
	abstract = {Optic disc drusen may be a cause of visual field defects and visual loss. The mechanism by which this occurs is unclear. We report a patient who developed decreased vision in the right eye and was found to have a heavy burden of superficial optic disc drusen. Optical coherence tomography (OCT) confirmed focal retinal nerve fiber layer thinning that corresponded with the distribution of drusen. OCT angiography, with superficial laminar segmentation, showed focal capillary attenuation overlying the most prominent drusen. These findings demonstrate alterations in the superficial retinal capillary network associated with optic disc drusen.},
	keywords = {Capillaries, Female, Fluorescein Angiography, Fundus Oculi, Humans, Middle Aged, Nerve Fibers, Optic Disk, Optic Disk Drusen, Retinal Ganglion Cells, Retinal Vessels, Scotoma, Tomography, Optical Coherence, Visual Acuity, Visual Fields},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000502},
	author = {Gaier, Eric D and Rizzo, Joseph F and Miller, John B and Cestari, Dean M}
}
@article {1439849,
	title = {Structural topology defines protective CD8 T cell epitopes in the HIV proteome},
	journal = {Science},
	volume = {364},
	number = {6439},
	year = {2019},
	month = {2019 05 03},
	pages = {480-484},
	abstract = {Mutationally constrained epitopes of variable pathogens represent promising targets for vaccine design but are not reliably identified by sequence conservation. In this study, we employed structure-based network analysis, which applies network theory to HIV protein structure data to quantitate the topological importance of individual amino acid residues. Mutation of residues at important network positions disproportionately impaired viral replication and occurred with high frequency in epitopes presented by protective human leukocyte antigen () class I alleles. Moreover, CD8 T cell targeting of highly networked epitopes distinguished individuals who naturally control HIV, even in the absence of protective alleles. This approach thereby provides a mechanistic basis for immune control and a means to identify CD8 T cell epitopes of topological importance for rational immunogen design, including a T cell-based HIV vaccine.},
	issn = {1095-9203},
	doi = {10.1126/science.aav5095},
	author = {Gaiha, Gaurav D and Rossin, Elizabeth J and Urbach, Jonathan and Landeros, Christian and Collins, David R and Nwonu, Chioma and Muzhingi, Itai and Anahtar, Melis N and Waring, Olivia M and Piechocka-Trocha, Alicja and Waring, Michael and Worrall, Daniel P and Ghebremichael, Musie S and Newman, Ruchi M and Power, Karen A and Allen, Todd M and Chodosh, James and Walker, Bruce D}
}
@article {1647879,
	title = {Treatment outcomes of first-ever episode of severe optic neuritis},
	journal = {Mult Scler Relat Disord},
	volume = {66},
	year = {2022},
	month = {2022 Oct},
	pages = {104020},
	abstract = {BACKGROUND: Severe optic neuritis (ON) is an acute inflammatory attack of the optic nerve(s) leading to severe visual loss that may occur in isolation or as part of a relapsing neuroinflammatory disease, such neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD), or more rarely multiple sclerosis (MS). In cases of first-ever severe ON of uncertain etiology best treatment strategies remain unclear. METHODS: We reviewed records of all patients with a documented diagnosis of ON between 2004 and 2019 at Mass General Brigham (MGB) and Johns Hopkins University (JHU) hospitals. Out of 381 patients identified, 90 (23.6\%) satisfied the study criteria for severe ON with visual acuity (VA) equal to or worse than 20/200 (logMAR=1) at nadir in the affected eye and had sufficient follow-up data. Treatment strategies with corticosteroids only or treatment escalation with therapeutic plasma exchange (PLEX) after steroids were compared and evaluated for differences in visual outcomes at follow-up. RESULTS: Of the 90 patients with severe optic neuritis, 71(78.9\%) received corticosteroids only, and 19 (17.0\%) underwent PLEX following corticosteroids. Of the 71 patients who received steroids without escalation to PLEX, 30 patients (42.2\%) achieved complete recovery (VA 20/20 on the affected eye), whereas 35 (49.3\%) had a partial recovery and 6 (8.4\%) had no recovery. Among the 19 corticosteroid non-responders patients who underwent escalation treatment, 13 (68.4\%) made complete recovery, 6 (31.6\%) had partial visual recoveries (p=0.0434). The median delta logMAR of patients who underwent escalation of care was -1.2 compared with 2.0 for the ones who did not (p=0.0208). A change of delta logmar 2.0 is equivalent of going from hand motion to light perception and the positive delta value refers to intra-attack worsening. Other than not responding to steroids, patients who underwent PLEX tended to have more severe ON with significantly worse nadir visual acuity compared with those who received corticosteroids alone (logMAR 3.12 (min 2.0 - max 5.0) vs. 2.17 (min 1.3 - max 3.0); p=0.004). CONCLUSION: In our cohort of first-ever severe optic neuritis of unknown etiology, patients that did not respond adequately to corticosteroids benefited from treatment escalation to PLEX, followed in most cases by Rituximab, regardless of final etiology. Randomized controlled trials are needed to confirm the best treatment strategies.},
	keywords = {Aquaporin 4, Autoantibodies, Humans, Myelin-Oligodendrocyte Glycoprotein, Neuromyelitis Optica, Optic Neuritis, Retrospective Studies, Rituximab, Steroids, Treatment Outcome},
	issn = {2211-0356},
	doi = {10.1016/j.msard.2022.104020},
	author = {Galetta, Kristin and Ryan, Sophia and Manzano, Giovanna and Chibnik, Lori B and Balaban, Denis and Prasad, Sashank and Chwalisz, Bart K and Salazar-Camelo, Andrea and Conway, Sarah and Michael Levy and Matiello, Marcelo}
}
@article {1359928,
	title = {White matter changes associated with cognitive visual dysfunctions in children with cerebral palsy: A diffusion tensor imaging study},
	journal = {J Neurosci Res},
	volume = {96},
	number = {11},
	year = {2018},
	month = {2018 Nov},
	pages = {1766-1774},
	abstract = {Children with cerebral palsy often present with cognitive-visual dysfunctions characterized by visuo-perceptual and/or visuo-spatial deficits associated with a malfunctioning of visual-associative areas. The neurofunctional model of this condition remains poorly understood due to the lack of a clear correlation between cognitive-visual deficit and morphological brain anomalies. The aim of our study was to quantify the pattern of white matter abnormalities within the whole brain in children with cerebral palsy, and to identify white matter tracts sub-serving cognitive-visual functions, in order to better understand the basis of cognitive-visual processing. Nine subjects (three males, mean age 8 years 9 months) with cerebral palsy underwent a visual and cognitive-visual evaluation. Conventional brain MRI and diffusion tensor imaging were performed. The fractional anisotropy maps were calculated for every child and compared with data from 13 (four males, mean age 10 years 7 months) healthy children. Children with cerebral palsy showed decreased fractional anisotropy (a marker of white matter integrity) in corticospinal tract bilaterally, left superior longitudinal fasciculus and bilateral hippocampus. Focusing on the superior longitudinal fasciculus, the mean fractional anisotropy values were significantly lower in children affected by cerebral palsy with cognitive-visual deficits than in those without cognitive-visual deficits. Our findings reveal an association between cognitive-visual profile and the superior longitudinal fasciculus integrity in children with cerebral palsy, supporting the hypothesis that visuo-associative deficits are related to changes in fibers connecting the occipital cortex with the parietal-frontal cortices. Decreased fractional anisotropy within the superior longitudinal fasciculus could be considered a biomarker for cognitive-visual dysfunctions.},
	issn = {1097-4547},
	doi = {10.1002/jnr.24307},
	author = {Galli, Jessica and Ambrosi, Claudia and Micheletti, Serena and Merabet, Lotfi B and Pinardi, Chiara and Gasparotti, Roberto and Fazzi, Elisa}
}
@article {1658660,
	title = {Neurovisual profile in children affected by Angelman syndrome},
	journal = {Brain Dev},
	volume = {45},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {117-125},
	abstract = {BACKGROUND: Angelman syndrome (AS) is a rare neurogenetic disorder caused by altered expression of the maternal copy of the UBE3A gene. Together with motor, cognitive, and speech impairment, ophthalmological findings including strabismus, and ocular fundus hypopigmentation characterize the clinical phenotype. The aim of this study was to detail the neurovisual profile of children affected by AS and to explore any possible genotype-phenotype correlations. METHODS: Thirty-seven children (23 females, mean age 102.8\&nbsp;{\textpm}\&nbsp;54.4\&nbsp;months, age range 22 to 251\&nbsp;months) with molecular confirmed diagnosis of AS were enrolled in the study. All underwent a comprehensive video-recorded neurovisual evaluation including the assessment of ophthalmological aspects, oculomotor functions, and basic visual abilities. RESULTS: All children had visual impairments mainly characterized by refractive errors, ocular fundus changes, strabismus, discontinuous/jerky smooth pursuit and altered saccadic movements, and/or reduced visual acuity. Comparing the neurovisual profiles between the deletion and non-deletion genetic subgroups, we found a significant statistical correlation between genotype and ocular fundus hypopigmentation (p\&nbsp;=\&nbsp;0.03), discontinuous smooth pursuit (p\&nbsp;\&lt;\&nbsp;0.05), and contrast sensitivity abnormalities (p\&nbsp;\&lt;\&nbsp;0.01) being more frequent in the deletion subgroup. CONCLUSIONS: Subjects affected by AS present a wide spectrum of neurovisual impairments that lead to a clinical profile consistent with cerebral visual impairment (CVI). Moreover, subjects with a chromosome deletion show a more severe visual phenotype with respect to ocular fundus changes, smooth pursuit movements, and contrast sensitivity. Early detection of these impaired visual functions may help promote the introduction of neurovisual habilitative programs which can improve children{\textquoteright}s visual, neuromotor, and cognitive outcomes.},
	keywords = {Angelman Syndrome, Female, Humans, Hypopigmentation, Ocular Motility Disorders, Strabismus, Vision Disorders},
	issn = {1872-7131},
	doi = {10.1016/j.braindev.2022.10.003},
	author = {Galli, Jessica and Loi, Erika and Strobio, Caterina and Micheletti, Serena and Martelli, Paola and Merabet, Lotfi B and Pasini, Nadia and Semeraro, Francesco and Fazzi, Elisa and AS Collaborative Group}
}
@article {1319467,
	title = {Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation},
	journal = {Nat Genet},
	volume = {50},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {956-967},
	abstract = {We apply integrative approaches to expression quantitative loci (eQTLs) from 44 tissues from the Genotype-Tissue Expression project and genome-wide association study data. About 60\% of known trait-associated loci are in linkage disequilibrium with a cis-eQTL, over half of which were not found in previous large-scale whole blood studies. Applying polygenic analyses to metabolic, cardiovascular, anthropometric, autoimmune, and neurodegenerative traits, we find that eQTLs are significantly enriched for trait associations in relevant pathogenic tissues and explain a substantial proportion of the heritability (40-80\%). For most traits, tissue-shared eQTLs underlie a greater proportion of trait associations, although tissue-specific eQTLs have a greater contribution to some traits, such as blood pressure. By integrating information from biological pathways with eQTL target genes and applying a gene-based approach, we validate previously implicated causal genes and pathways, and propose new variant and gene associations for several complex traits, which we replicate in the UK BioBank and BioVU.},
	issn = {1546-1718},
	doi = {10.1038/s41588-018-0154-4},
	author = {Gamazon, Eric R and Segr{\`e}, Ayellet V and van de Bunt, Martijn and Wen, Xiaoquan and Xi, Hualin S and Hormozdiari, Farhad and Ongen, Halit and Konkashbaev, Anuar and Derks, Eske M and Aguet, Fran{\c c}ois and Quan, Jie and GTEx Consortium and Nicolae, Dan L and Eskin, Eleazar and Kellis, Manolis and Getz, Gad and McCarthy, Mark I and Dermitzakis, Emmanouil T and Cox, Nancy J and Ardlie, Kristin G}
}
@article {1125301,
	title = {Emotion processing in early blind and sighted individuals},
	journal = {Neuropsychology},
	volume = {31},
	number = {5},
	year = {2017},
	month = {2017 Jul},
	pages = {516-524},
	abstract = {OBJECTIVE: Emotion processing is known to be mediated by a complex network of cortical and subcortical regions with evidence of specialized hemispheric lateralization within the brain. In light of prior evidence indicating that lateralization of cognitive functions (such as language) may depend on normal visual development, we investigated whether the lack of prior visual experience would have an impact on the development of specialized hemispheric lateralization in emotional processing. METHOD: We addressed this issue by comparing performance in early blind and sighted controls on a dichotic listening task requiring the detection of specific emotional vocalizations (i.e., suggestive of happiness or sadness) presented independently to either ear. RESULTS: Consistent with previous studies, we found that sighted individuals showed enhanced detection of positive vocalizations when presented in the right ear (i.e., processed within the left hemisphere) and negative vocalizations when presented in the left ear (i.e., right hemisphere). It is interesting to note that although blind individuals were as accurate as sighted controls in detecting the valance of the vocalization, performance was not consistent with any pattern of specialized hemispheric lateralization. CONCLUSIONS: Overall, these results suggest that although the lack of prior visual experience may not lead to impaired emotion processing performance, the underlying neurophysiological substrate (i.e., degree of special hemispheric lateralization) may depend on normal visual development. (PsycINFO Database Record},
	issn = {1931-1559},
	doi = {10.1037/neu0000360},
	author = {Gamond, Lucile and Vecchi, Tomaso and Ferrari, Chiara and Merabet, Lotfi B and Cattaneo, Zaira}
}
@article {1452952,
	title = {Comparison Between Methotrexate and Mycophenolate Mofetil Monotherapy for the Control of Noninfectious Ocular Inflammatory Diseases},
	journal = {Am J Ophthalmol},
	volume = {208},
	year = {2019},
	month = {2019 Dec},
	pages = {68-75},
	abstract = {PURPOSE: To compare mycophenolate mofetil (MMF) to methotrexate (MTX) as corticosteroid-sparing therapy for ocular inflammatory diseases. DESIGN: Retrospective analysis of cohort study data. METHODS: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained via medical record review. The study included 352 patients who were taking single-agent immunosuppression with MTX or MMF at 4 tertiary uveitis clinics. Marginal structural models (MSM)-derived statistical weighting created a virtual population with covariates and censoring patterns balanced across alternative treatments. With this methodological approach, the results estimate what would have happened had none of the patients stopped their treatment. Survival analysis with stabilized MSM-derived weights simulated a clinical trial comparing MMF vs MTX for noninfectious inflammatory eye disorders. The primary outcome was complete control of inflammation on prednisone <=10\&nbsp;mg/day, sustained for >=30\&nbsp;days. RESULTS: The time to success was shorter (more favorable) for MMF than MTX (hazard ratio\&nbsp;= 0.68, 95\%\&nbsp;confidence interval: 0.46-0.99). Adjusting for covariates, the proportion achieving success was higher at every point in time for MMF than MTX from 2 to 8\&nbsp;months, then converges at 9\&nbsp;months. The onset of corticosteroid-sparing success took more than 3\&nbsp;months for most patients in both groups. Outcomes of treatment (MMF vs MTX) were similar across all anatomic sites of inflammation. The incidence of stopping therapy for toxicity was similar in both groups. CONCLUSIONS: Our results suggest that, on average, MMF may be faster than MTX in achieving corticosteroid-sparing success in ocular inflammatory diseases.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.07.008},
	author = {Gangaputra, Sapna S and Newcomb, Craig W and Joffe, Marshall M and Dreger, Kurt and Begum, Hosne and Artornsombudh, Pichaporn and Pujari, Siddharth S and Daniel, Ebenezer and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Bhatt, Nirali P and Foster, C Stephen and Jabs, Douglas A and Nussenblatt, Robert B and Rosenbaum, James T and Levy-Clarke, Grace A and Kempen, John H and SITE Cohort Research Group}
}
@article {1667691,
	title = {Long-term visual acuity outcomes following cataract surgery in eyes with ocular inflammatory disease},
	journal = {Br J Ophthalmol},
	volume = {108},
	number = {3},
	year = {2024},
	month = {2024 Feb 21},
	pages = {380-385},
	abstract = {PURPOSE: To evaluate the long-term visual acuity (VA) outcome of cataract surgery in inflammatory eye disease. SETTING: Tertiary care academic centres. DESIGN: Multicentre retrospective cohort study. METHODS: A total of 1741 patients with non-infectious inflammatory eye disease (2382 eyes) who underwent cataract surgery while under tertiary uveitis management were included. Standardised chart review was used to gather clinical data. Multivariable logistic regression models with adjustment for intereye correlations were performed to evaluate the prognostic factors for VA outcomes. Main outcome measure was VA after cataract surgery. RESULTS: Uveitic eyes independent of anatomical location showed improved VA from baseline (mean 20/200) to within 3 months (mean 20/63) of cataract surgery and maintained through at least 5 years of follow-up (mean 20/63). Eyes that achieved 20/40 or better VA at 1 year were more likely to have scleritis (OR=1.34, p\&lt;0.0001) or anterior uveitis (OR=2.2, p\&lt;0.0001), VA 20/50 to 20/80 (OR 4.76 as compared with worse than 20/200, p\&lt;0.0001) preoperatively, inactive uveitis (OR=1.49, p=0.03), have undergone phacoemulsification (OR=1.45 as compared with extracapsular cataract extraction, p=0.04) or have had intraocular lens placement (OR=2.13, p=0.01). Adults had better VA immediately after surgery, with only 39\% (57/146) paediatric eyes at 20/40 or better at 1 year. CONCLUSIONS: Our results suggest that adult and paediatric eyes with uveitis typically have improved VA following cataract surgery and remain stable thereafter for at least 5 years.},
	keywords = {Adult, Cataract, Cataract Extraction, Child, Conjunctival Diseases, Humans, Phacoemulsification, Retrospective Studies, Treatment Outcome, Uveitis, Vision Disorders, Visual Acuity},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-322236},
	author = {Gangaputra, Sapna and Newcomb, Craig and Armour, Rebecca and Choi, Dongseok and Ying, Gui-Shuang and Groth, Sylvia and Begum, Hosne and Fitzgerald, Tonetta and Artornsombudh, Pichaporn and Daniel, Ebenezer and Bhatt, Nirali and Foster, Stephen and Jabs, Douglas and Levy-Clarke, Grace and Nussenblatt, Robert and Rosenbaum, James T and Sen, H Nida and Suhler, Eric and Thorne, Jennifer and Dreger, Kurt and Buchanich, Jeanine and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Research Group}
}
@article {913451,
	title = {Genome-Wide Association Study Identifies WNT7B as a Novel Locus for Central Corneal Thickness in Latinos.},
	journal = {Hum Mol Genet},
	year = {2016},
	month = {2016 Sep 20},
	abstract = {The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (\~{}730K markers) or the Illumina Hispanic/SOL BeadChip (\~{}2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender, and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P = 6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1, and ZNF469 (P \&lt; 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddw319},
	author = {Gao, Xiaoyi and Nannini, Drew R and Corrao, Kristen and Torres, Mina and Chen, Yii-Der I and Fan, Bao J and Wiggs, Janey L and International Glaucoma Genetics Consortium and Taylor, Kent D and James Gauderman, W and Rotter, Jerome I and Varma, Rohit}
}
@article {655091,
	title = {Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure.},
	journal = {Am J Pathol},
	volume = {186},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {985-1005},
	abstract = {A genomic region located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a transgenic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50\% in the heterozygous mice and by 90\% in the homozygous mice, which suggested that the CDKN2B knock down had no deleterious consequences for the retina under normal conditions. However, compared with wild-type and heterozygous animals, the homozygous mice are more vulnerable to retinal ganglion cell loss in response to elevated intraocular pressure.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2015.11.026},
	author = {Gao, Shan and Jakobs, Tatjana C}
}
@article {1619409,
	title = {Ocular Penetrance and Safety of the Dopaminergic Prodrug Etilevodopa},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {12},
	year = {2021},
	month = {2021 10 04},
	pages = {5},
	abstract = {Purpose: Animal models have demonstrated the role of dopamine in regulating axial elongation, the critical feature of myopia. Because frequent delivery of dopaminergic agents via peribulbar, intravitreal, or intraperitoneal injections is not clinically viable, we sought to evaluate ocular penetration and safety of the topically applied dopaminergic prodrug etilevodopa. Methods: The ocular penetration of dopamine and dopaminergic prodrugs (levodopa and etilevodopa) were quantified using an enzyme-linked immunosorbent assay in enucleated porcine eyes after a single topical administration. The pharmacokinetic profile of the etilevodopa was then assessed in rats. A four-week once-daily application of etilevodopa as a topical eye drop was conducted to establish its safety profile. Results: At 24\&nbsp;hours, the studied prodrugs showed increased dopaminergic derivatives in the vitreous of porcine eyes. Dopamine 0.5\% (P = 0.0123) and etilevodopa 10\% (p = 0.370) achieved significant vitreous concentrations. Etilevodopa 10\% was able to enter the posterior segment of the eye after topical administration in rats with an intravitreal half-life of eight hours after single topical administration. Monthly application of topical etilevodopa showed no alterations in retinal ocular coherence tomography, electroretinography, caspase staining, or TUNEL staining. Conclusions: At similar concentrations, no difference in ocular penetration of levodopa and etilevodopa was observed. However, etilevodopa was highly soluble and able to be applied at higher topical concentrations. Dopamine exhibited both high solubility and enhanced penetration into the vitreous as compared to other dopaminergic prodrugs. Translational Relevance: These findings indicate the potential of topical etilevodopa and dopamine for further study as a therapeutic treatment for myopia.},
	keywords = {Animals, Dopamine, Levodopa, Penetrance, Prodrugs, Rats, Retina, Swine},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.12.5},
	author = {Gao, Quanqing and Ludwig, Cassie A and Smith, Stephen J and Schachar, Ira H}
}
@article {1347435,
	title = {Correcting geometric distortions in stereoscopic 3D imaging},
	journal = {PLoS One},
	volume = {13},
	number = {10},
	year = {2018},
	month = {2018},
	pages = {e0205032},
	abstract = {Motion in a distorted virtual 3D space may cause visually induced motion sickness. Geometric distortions in stereoscopic 3D can result from mismatches among image capture, display, and viewing parameters. Three pairs of potential mismatches are considered, including 1) camera separation vs. eye separation, 2) camera field of view (FOV) vs. screen FOV, and 3) camera convergence distance (i.e., distance from the cameras to the point where the convergence axes intersect) vs. screen distance from the observer. The effect of the viewer{\textquoteright}s head positions (i.e., head lateral offset from the screen center) is also considered. The geometric model is expressed as a function of camera convergence distance, the ratios of the three parameter-pairs, and the offset of the head position. We analyze the impacts of these five variables separately and their interactions on geometric distortions. This model facilitates insights into the various distortions and leads to methods whereby the user can minimize geometric distortions caused by some parameter-pair mismatches through adjusting of other parameter pairs. For example, in postproduction, viewers can correct for a mismatch between camera separation and eye separation by adjusting their distance from the real screen and changing the effective camera convergence distance.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0205032},
	author = {Gao, Zhongpai and Hwang, Alex and Zhai, Guangtao and Peli, Eli}
}
@article {694766,
	title = {In vitro and in vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery.},
	journal = {Hum Mol Genet},
	year = {2016},
	month = {2016 Apr 22},
	abstract = {Leber congenital amaurosis (LCA) is a severe disorder resulting in visual impairment usually starting in the first year of life. The most frequent genetic cause of LCA is an intronic mutation in CEP290 (c.2991+1655A\&gt;G) that creates a cryptic splice donor site resulting in the insertion of a pseudoexon (exon X) into CEP290 mRNA. Previously, we showed that naked antisense oligonucleotides (AONs) effectively restored normal CEP290 splicing in patient-derived lymphoblastoid cells. We here explore the therapeutic potential treatment of naked and AAV-packaged AONs in vitro and in vivo In both cases, AON delivery fully restored CEP290 pre-mRNA splicing, significantly increased CEP290 protein levels and rescued a ciliary phenotype present in patient-derived fibroblast cells. Moreover, administration of naked and AAV-packaged AONs to the retina of a humanized mutant Cep290 mouse model, carrying the intronic mutation, showed a statistically significant reduction of exon X-containing Cep290 transcripts, without compromising the retinal structure. Together, our data highlight the tremendous therapeutic prospective of AONs for the treatment of not only CEP290-associated LCA but potentially many other subtypes of retinal dystrophy caused by splicing mutations.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddw118},
	author = {Garanto, Alejandro and Chung, Daniel C and Duijkers, Lonneke and Corral-Serrano, Julio C and Messchaert, Muri{\"e}l and Xiao, Ru and Bennett, Jean and Vandenberghe, Luk H and Collin, Rob W J}
}
@article {468951,
	title = {Aniseikonia Tests: The Role of Viewing Mode, Response Bias, and Size-Color Illusions.},
	journal = {Transl Vis Sci Technol},
	volume = {4},
	number = {3},
	year = {2015},
	month = {2015 Jun},
	pages = {9},
	abstract = {PURPOSE: To identify the factors responsible for the poor validity of the most common aniseikonia tests, which involve size comparisons of red-green stimuli presented haploscopically. METHODS: Aniseikonia was induced by afocal size lenses placed before one eye. Observers compared the sizes of semicircles presented haploscopically via color filters. The main factor under study was viewing mode (free viewing versus short presentations under central fixation). To eliminate response bias, a three-response format allowed observers to respond if the left, the right, or neither semicircle appeared larger than the other. To control decisional (criterion) bias, measurements were taken with the lens-magnified stimulus placed on the left and on the right. To control for size-color illusions, measurements were made with color filters in both arrangements before the eyes and under binocular vision (without color filters). RESULTS: Free viewing resulted in a systematic underestimation of lens-induced aniseikonia that was absent with short presentations. Significant size-color illusions and decisional biases were found that would be mistaken for aniseikonia unless appropriate action is taken. CONCLUSIONS: To improve their validity, aniseikonia tests should use short presentations and include control conditions to prevent contamination from decisional/response biases. If anaglyphs are used, presence of size-color illusions must be checked for. TRANSLATIONAL RELEVANCE: We identified optimal conditions for administration of aniseikonia tests and appropriate action for differential diagnosis of aniseikonia in the presence of response biases or size-color illusions. Our study has clinical implications for aniseikonia management.},
	issn = {2164-2591},
	doi = {10.1167/tvst.4.3.9},
	author = {Garc{\'\i}a-P{\'e}rez, Miguel A and Peli, Eli}
}
@article {504066,
	title = {Interaction of IFN-γ with cholinergic agonists to modulate rat and human goblet cell function.},
	journal = {Mucosal Immunol},
	volume = {9},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {206-17},
	abstract = {Goblet cells populate wet-surfaced mucosa including the conjunctiva of the eye, intestine, and nose, among others. These cells function as part of the innate immune system by secreting high molecular weight mucins that interact with environmental constituents including pathogens, allergens, and particulate pollutants. Herein, we determined whether interferon gamma (IFN-γ), a Th1 cytokine increased in dry eye, alters goblet cell function. Goblet cells from rat and human conjunctiva were cultured. Changes in intracellular [Ca(2+)] ([Ca(2+)]i), high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with IFN-γ with or without the cholinergic agonist carbachol. IFN-γ itself increased [Ca(2+)]i in rat and human goblet cells and prevented the increase in [Ca(2+)]i caused by carbachol. Carbachol prevented IFN-γ-mediated increase in [Ca(2+)]i. This cross-talk between IFN-γ and muscarinic receptors may be partially due to use of the same Ca(2+)i reservoirs, but also from interaction of signaling pathways proximal to the increase in [Ca(2+)]i. IFN-γ blocked carbachol-induced high molecular weight glycoconjugate secretion and reduced goblet cell proliferation. We conclude that increased levels of IFN-γ in dry eye disease could explain the lack of goblet cells and mucin deficiency typically found in this pathology. IFN-γ could also function similarly in respiratory and gastrointestinal tracts.},
	issn = {1935-3456},
	doi = {10.1038/mi.2015.53},
	author = {Garc{\'\i}a-Posadas, L and Hodges, R R and Li, D and Shatos, M A and Storr-Paulsen, T and Diebold, Y and Dartt, D A}
}
@article {1328880,
	title = {Context-Dependent Regulation of Conjunctival Goblet Cell Function by Allergic Mediators},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Aug 15},
	pages = {12162},
	abstract = {In the eye, goblet cells responsible for secreting mucins are found in the conjunctiva. When mucin production is not tightly regulated several ocular surface disorders may occur. In this study, the effect of the T helper (Th) 2-type cytokines IL4, IL5, and IL13 on conjunctival goblet cell function was explored. Goblet cells from rat conjunctiva were cultured and characterized. The presence of cytokine receptors was confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Changes in intracellular [Ca], high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with Th2 cytokines with or without the allergic mediator histamine. We found that IL4 and IL13 enhance cell proliferation and, along with histamine, stimulate goblet cell secretion. We conclude that the high levels of IL4, IL5, and IL13 that characterize allergic conjunctivitis could be the reason for higher numbers of goblet cells and mucin overproduction found in this condition.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-30002-x},
	author = {Garc{\'\i}a-Posadas, Laura and Hodges, Robin R and Diebold, Yolanda and Dartt, Darlene A.}
}
@article {669271,
	title = {Conjunctival Goblet Cell Function: Effect of Contact Lens Wear and Cytokines.},
	journal = {Eye Contact Lens},
	volume = {42},
	number = {2},
	year = {2016},
	month = {2016 Mar},
	pages = {83-90},
	abstract = {This review focuses on conjunctival goblet cells and their essential function in the maintenance of eye health. The main function of goblet cells is to produce and secrete mucins that lubricate the ocular surface. An excess or a defect in those mucins leads to several alterations that makes goblet cells central players in maintaining the proper mucin balance and ensuring the correct function of ocular surface tissues. A typical pathology that occurs with mucous deficiency is dry eye disease, whereas the classical example of mucous hyperproduction is allergic conjunctivitis. In this review, we analyze how goblet cell number and function can be altered in these diseases and in contact lens (CL) wearers. We found that most published studies focused exclusively on the goblet cell number. However, recent advances have demonstrated that, along with mucin secretion, goblet cells are also able to secrete cytokines and respond to them. We describe the effect of different cytokines on goblet cell proliferation and secretion. We conclude that it is important to further explore the effect of CL wear and cytokines on conjunctival goblet cell function.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000158},
	author = {Garc{\'\i}a-Posadas, Laura and Contreras-Ruiz, Laura and Soriano-Roman{\'\i}, Laura and Dartt, Darlene A. and Diebold, Yolanda}
}
@article {1522729,
	title = {Lacrimal Gland Myoepithelial Cells Are Altered in a Mouse Model of Dry Eye Disease},
	journal = {Am J Pathol},
	volume = {190},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {2067-2079},
	abstract = {The purpose of this study was to determine the pathogenic changes that occur in myoepithelial cells (MECs) from lacrimal glands of a mouse model of Sj{\"o}gren syndrome. MECs were cultured from lacrimal glands of C57BL/6J [wild type (WT)] and thrombospondin 1 null (TSP1, alias Thbs1) mice and from mice expressing α-smooth muscle actin-green fluorescent protein that labels MECs. MECs were stimulated with cholinergic and α-adrenergic agonists, vasoactive intestinal peptide (VIP), and the purinergic agonists ATP and UTP. Then intracellular [Ca] was measured using fura-2, and contraction was observed using live cell imaging. Expression of purinergic receptors was determined by Western blot analysis, and mRNA expression was analyzed by microarray. The increase in intracellular [Ca] with VIP and UTP was significantly smaller in MECs from TSP1 compared with WT mice. Cholinergic agonists, ATP, and UTP stimulated contraction in MECs, although contraction of MECs from TSP1 mice was reduced compared with WT mice. The amount of purinergic receptors P2Y1, P2Y11, and P2Y13 was significantly decreased in MECs from TSP1 compared with WT mice, whereas several extracellular matrix and inflammation genes were up-regulated in MECs from TSP1 mice. We conclude that lacrimal gland MEC function is altered by inflammation because the functions regulated by cholinergic agonists, VIP, and\&nbsp;purinergic receptors are decreased in TSP1 compared with WT mice.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.06.013},
	author = {Garc{\'\i}a-Posadas, Laura and Hodges, Robin R and Utheim, Tor P and Olstad, Ole Kristoffer and Delcroix, Vanessa and Makarenkova, Helen P and Dartt, Darlene A.}
}
@article {836831,
	title = {Homologous Recombination within Large Chromosomal Regions Facilitates Acquisition of β-Lactam and Vancomycin Resistance in Enterococcus faecium.},
	journal = {Antimicrob Agents Chemother},
	volume = {60},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {5777-86},
	abstract = {The transfer of DNA between Enterococcus faecium strains has been characterized both by the movement of well-defined genetic elements and by the large-scale transfer of genomic DNA fragments. In this work, we report on the whole-genome analysis of transconjugants resulting from mating events between the vancomycin-resistant E. faecium C68 strain and the vancomycin-susceptible D344RRF strain to discern the mechanism by which the transferred regions enter the recipient chromosome. Vancomycin-resistant transconjugants from five independent matings were analyzed by whole-genome sequencing. In all cases but one, the penicillin binding protein 5 (pbp5) gene and the Tn5382 vancomycin resistance transposon were transferred together and replaced the corresponding pbp5 region of D344RRF. In one instance, Tn5382 inserted independently downstream of the D344RRF pbp5 gene. Single nucleotide variant (SNV) analysis suggested that entry of donor DNA into the recipient chromosome occurred by recombination across regions of homology between donor and recipient chromosomes, rather than through insertion sequence-mediated transposition. The transfer of genomic DNA was also associated with the transfer of C68 plasmid pLRM23 and another putative plasmid. Our data are consistent with the initiation of transfer by cointegration of a transferable plasmid with the donor chromosome, with subsequent circularization of the plasmid-chromosome cointegrant in the donor prior to transfer. Entry into the recipient chromosome most commonly occurred across regions of homology between donor and recipient chromosomes.},
	issn = {1098-6596},
	doi = {10.1128/AAC.00488-16},
	author = {Garc{\'\i}a-Solache, M{\'o}nica and Lebreton, Francois and McLaughlin, Robert E and Whiteaker, James D and Gilmore, Michael S and Rice, Louis B}
}
@article {1632286,
	title = {Clinicians{\textquoteright} Use of Quantitative Information When Assessing the Rate of Structural Progression in Glaucoma},
	journal = {Ophthalmol Glaucoma},
	volume = {5},
	number = {5},
	year = {2022},
	month = {2022 Sep-Oct},
	pages = {507-515},
	abstract = {PURPOSE: OCT scans contain large amounts of information, but clinicians often rely on reported layer thicknesses when assessing the rate of glaucomatous progression. We sought to determine which of these quantifications most closely relate to the subjective assessment of glaucoma experts who had all the diagnostic information available. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven glaucoma specialists independently scored the rate of structural progression from a series of 5 biannual clinical OCT printouts. METHODS: A total of 100 glaucoma or glaucoma suspect eyes of 51 participants were included; 20 were scored twice to assess repeatability. Scores ranged from 1 (improvement) to 7 (very rapid progression). Generalized estimating equation linear models were used to predict the mean clinician score from the rates of change of retinal nerve fiber layer thickness (RNFLT) or minimum rim width (MRW) globally or in the most rapidly thinning of the 6 sectors. MAIN OUTCOME MEASURES: The correlation between the objective rates of change and the average of the 11 clinicians{\textquoteright} scores. RESULTS: Average RNFLT within the series of study eyes was 79.3 μm (range, 41.4-126.6). Some 95\% of individual clinician scores varied by <= 1 point when repeated. The mean clinician score was more strongly correlated with the rate of change of RNFLT in the most rapidly changing sector in \%/year (pseudo-R2\&nbsp;= 0.657) than the rate of global RNFLT (0.372). The rate of MRW in the most rapidly changing sector had pseudo-R2\&nbsp;= 0.149. CONCLUSIONS: The rate of change of RNFLT in the most rapidly changing sector predicted experts{\textquoteright} assessment of the rate of structural progression better than global rates or MRW. Sectoral rates may be a useful addition to current clinical printouts.},
	keywords = {Glaucoma, Humans, Intraocular Pressure, Nerve Fibers, Optic Disk, Prospective Studies, Retinal Ganglion Cells, Tomography, Optical Coherence},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.02.001},
	author = {Gardiner, Stuart K and Kinast, Robert M and Chen, Teresa C and Strouthidis, Nicholas G and De Moraes, Carlos Gustavo and Nouri-Mahdavi, Kouros and Myers, Jonathan S and Jeoung, Jin Wook and Lind, John T and Rhodes, Lindsay A and Budenz, Donald L and Mansberger, Steven L}
}
@article {1635659,
	title = {Clinicians{\textquoteright} Use of Quantitative Information while Assessing the Rate of Functional Progression in Glaucoma},
	journal = {Ophthalmol Glaucoma},
	volume = {5},
	number = {5},
	year = {2022},
	month = {2022 Sep-Oct},
	pages = {498-506},
	abstract = {PURPOSE: Clinicians use both global and point-wise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlated with subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change vs. on global indices reported by the perimeter. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven academic, expert glaucoma specialists independently scored the rate of functional progression, from 1 (improvement) to 7 (very rapid progression), for a series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability. METHODS: Regression models were used to predict the average of the 11 clinicians{\textquoteright} scores based on objective rates of change of mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of 10 anatomically defined clusters of locations after weighting by eccentricity. MAIN OUTCOME MEASURES: Correlation between the objective rates of change and the average of the 11 clinicians{\textquoteright} scores. RESULTS: The average MD of the study eyes was\&nbsp;-2.4 dB (range,\&nbsp;-16.8 to\&nbsp;+2.8 dB). The mean clinician score was highly repeatable, with an intraclass correlation coefficient of 0.95. It correlated better with the rate of change of VFI (pseudo-R2\&nbsp;= 0.73, 95\% confidence interval [CI, 0.60-0.83]) than with MD (pseudo-R2\&nbsp;= 0.63, 95\% CI [0.45-0.76]) or PSD (pseudo-R2\&nbsp;= 0.41, 95\% CI [0.26-0.55]). Using point-wise information, the highest correlations were found with the fifth-fastest progressing location (pseudo-R2\&nbsp;= 0.71, 95\% CI [0.56-0.80]) and the fastest-progressing cluster after eccentricity weighting (pseudo-R2\&nbsp;= 0.61, 95\% CI [0.48-0.72]). Among 25 eyes with an average VFI of \&gt; 99\%, the highest observed pseudo-R2 value was 0.34 (95\% CI [0.16-0.61]) for PSD. CONCLUSIONS: Expert academic glaucoma specialists{\textquoteright} assessment of the rate of change correlated best with VFI rates, except in eyes with a VFI near the ceiling of 100\%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but the experts{\textquoteright} opinions correlated more closely with global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.},
	keywords = {Disease Progression, Glaucoma, Humans, Prospective Studies, Vision Disorders, Visual Field Tests},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.03.002},
	author = {Gardiner, Stuart K and Kinast, Robert M and De Moraes, Carlos Gustavo and Budenz, Donald L and Jeoung, Jin Wook and Lind, John T and Myers, Jonathan S and Nouri-Mahdavi, Kouros and Rhodes, Lindsay A and Strouthidis, Nicholas G and Chen, Teresa C and Mansberger, Steven L}
}
@article {1709726,
	title = {Semi-automated algorithm using directional filter for the precise quantification of non-perfusion area on widefield swept-source optical coherence tomography angiograms},
	journal = {Quant Imaging Med Surg},
	volume = {13},
	number = {6},
	year = {2023},
	month = {2023 Jun 01},
	pages = {3688-3702},
	abstract = {BACKGROUND: The clinical application of optical coherence tomography angiography (OCTA) has been well documented in literature with its promising potential in dye-less evaluation of various retinal vascular pathologies. Recent advances in OCTA help us gather wider field of view with 12 mm {\texttimes} 12 mm and montage compared to the standard dye-based scans, which has a higher accuracy and sensitivity in detection of peripheral pathologies. The aim of this study is to build a semi-automated algorithm to precisely quantify the non-perfusion areas (NPAs) on widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: All subjects underwent imaging on 100 kHz SS-OCTA device acquiring 12 mm {\texttimes} 12 mm angiograms centered on fovea and optic disc. After a comprehensive literature review, a novel algorithm using FIJI (ImageJ) was designed to calculate the NPAs (mm2) after excluding the threshold and segmentation artifact areas from the total field of view. Segmentation and threshold artifacts were first removed from enface structure images using the spatial variance and mean filter respectively. Vessel enhancement was achieved by using {\textquoteright}Subtract Background{\textquoteright} followed by directional filter. The cut off for Huang{\textquoteright}s fuzzy black and white thresholding was defined from the pixel values based of the foveal avascular zone. Then, the NPAs were calculated using the {\textquoteright}Analyze Particles{\textquoteright} command with a minimum size of ~0.15 mm2. Finally, the artifact area was subtracted from to give the corrected NPAs. RESULTS: Our cohort had 44 eyes of 30 control patients and 107 eyes of 73 patients with diabetes mellitus (both median age 55 years, P=0.89). Of 107 eyes, 21 eyes had no evidence of diabetic retinopathy (DR), 50 eyes had non-proliferative DR and 36 eyes had proliferative DR. The median NPA was 0.20 (0.07-0.40) in controls, 0.28 (0.12-0.72) in no DR, 5.54 (3.12-9.10) in non-proliferative DR and 13.38 (8.73-26.32) in proliferative DR eyes. Using mixed effects-multiple linear regression analysis adjusting for age, there was significant progressive increase in NPA with increasing DR severity. CONCLUSIONS: This is one of the first study to use the directional filter for WFSS-OCTA image processing which is known to be superior to other Hessian based multiscale, linear, and non-linear filters especially for vascular analysis. Our method could greatly refine and streamline the calculation of signal void area proportion, while being much quicker and accurate than manual delineation of NPAs and subsequent estimation. This combined with the wide field of view can have a great prognostic and diagnostic clinical impact for future applications in DR and other ischemic retinal pathologies.},
	issn = {2223-4292},
	doi = {10.21037/qims-21-1175},
	author = {Garg, Itika and Miller, John B}
}
@article {1645470,
	title = {Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {2},
	year = {2022},
	month = {2022 Jun},
	abstract = {Purpose: To study the wider field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, especially non-perfusion area (NPA), in the diagnosing and staging of DR. Design: Cross-sectional observational study (November 2018-September 2020). Participants: 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients). Methods: We imaged using 6mm{\texttimes}6mm and 12mm{\texttimes}12mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operator characteristic analysis was used for statistical analyses. Main Outcome Measures: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading. Results: Among patients with diabetes (median age 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had non-proliferative DR (NPDR); and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. NPA was the best parameter to diagnose DR (AUC:0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC:0.97) and differentiated between DR stages (AUC range:0.83-0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas an increased VD and VSD in SCP among moderate-severe NPDR group. Conclusions: Our work highlights the importance of NPA, which can be more readily and easily measured with WF SS-OCTA compared to fluorescein angiography. It is additionally quick and non-invasive, and hence can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6mm{\texttimes}6mm and 12mm{\texttimes}12mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100144},
	author = {Garg, Itika and Uwakwe, Chibuike and Le, Rongrong and Lu, Edward S and Cui, Ying and Wai, Karen M and Katz, Raviv and Zhu, Ying and Moon, Jade Y and Li, Chloe Y and La{\'\i}ns, In{\^e}s and Eliott, Dean and Tobias Elze and Kim, Leo A and Wu, David M and Miller, Joan W and Husain, Deeba and Vavvas, Demetrios G and Miller, John B}
}
@article {1623364,
	title = {Role of the Phospholipase C Pathway and Calcium Mobilization in Oxytocin-Induced Contraction of Lacrimal Gland Myoepithelial Cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {62},
	number = {14},
	year = {2021},
	month = {2021 11 01},
	pages = {25},
	abstract = {Purpose: We reported that oxytocin (OXT), added to freshly prepared lacrimal gland lobules, induced myoepithelial cell (MEC) contraction. In other systems, OXT activates phospholipase C (PLC) generating Inositol 1,4,5-trisphosphate (IP3) which increases intracellular calcium concentration ([Ca2+]i) causing contraction. The aim of the current study was to investigate the role of this pathway in OXT-induced contraction of MEC. Methods: Tear volume was measured using the cotton thread method. Lacrimal gland MEC were isolated and propagated from α-smooth muscle actin (SMA)-green fluorescent protein (GFP) mice, in which MEC express GFP making them easily identifiable. RNA and protein samples were prepared for RT-PCR and Western blotting for G protein expression. Changes in [Ca2+]i were measured in Fura-2 loaded MEC using a ratio imaging system. MEC contraction was monitored in real time and changes in cell size were quantified using ImageJ software. Results: OXT applied either topically to surgically exposed lacrimal glands or delivered subcutaneously resulted in increased tear volume. OXT stimulated lacrimal gland MEC contraction in a dose-dependent manner, with a maximum response at 10-7 M. MEC express the PLC coupling G proteins, Gαq and Gα11, and their activation by OXT resulted in a concentration-dependent increase in [Ca2+]i with a maximum response at 10-6 M. Furthermore, the activation of the IP3 receptor to increase [Ca2+]i is crucial for OXT-induced MEC contraction since blocking the IP3 receptor with 2-APB completely abrogated this response. Conclusions: We conclude that OXT uses the PLC/Ca2+ pathway to stimulate MEC contraction and increase lacrimal gland secretion.},
	issn = {1552-5783},
	doi = {10.1167/iovs.62.14.25},
	author = {G{\'a}rriz, Angela and Aubry, Salome and Wattiaux, Quentin and Bair, Jeffrey and Mariano, Michael and Hatzipetrou, Georgios and Bowman, Maytal and Morokuma, Junji and Ortiz, Gustavo and Hamrah, Pedram and Dartt, Darlene A. and Zoukhri, Driss}
}
@article {1435400,
	title = {Translation and validation of the contact lens dry eye questionnaire-8 (CLDEQ-8) to the Spanish language},
	journal = {Cont Lens Anterior Eye},
	volume = {42},
	number = {2},
	year = {2019},
	month = {2019 Apr},
	pages = {155-158},
	abstract = {PURPOSE: To present the process of cultural and psychometric adaptation, and clinical validation of a new version in the Spanish language of the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8). MATERIALS AND METHODS: The translation-retro-translation method was applied to the CLDEQ-8 questionnaire. Two independent native Spanish-speaking translators adapted the questionnaire from English to Spanish, and then a committee of experienced clinicians (CE) evaluated the semantic equivalence and designed a Spanish version of the CLDEQ-8 questionnaire. The resulting translated version was tested conducting a pilot study in contact lens users and assessing their perception and overall understanding of the terminology. The results were analyzed and a final version was designed. The final version was retro-translated to English by a native English-speaking translator and compared with the original CLDEQ-8 version to confirm there were no meaningful differences. To clinically validate the new instrument, a prospective study was conducted to apply the new Spanish CLDEQ-8 to 50 contact lens users. RESULTS: Fifty patients were studied with an average age of 21.50 {\textpm} 1.66 years. The average CLDEQ-8 score was 13.28 {\textpm} 6.81 points (range 1-31). The internal consistency (Cronbach{\textquoteright}s alpha) was 0.89, with a corrected index of homogeneity \&gt;0.50 for all evaluated items. CONCLUSIONS: The process of trans-cultural adaptation of the questionnaire CLDEQ-8 resulted in the elaboration of a reliable and much needed instrument capable of measuring frequency and intensity of dry eye symptoms in Spanish-speaking contact lens users.},
	issn = {1476-5411},
	doi = {10.1016/j.clae.2018.10.015},
	author = {Garza-Leon, Manuel and Amparo, Francisco and Ort{\'\i}z, Gabriela and de la Parra-Colin, Paola and Sanchez-Huerta, Valeria and Beltran, Francisco and Hernandez-Quintela, Everardo}
}
@article {1478331,
	title = {Childhood glaucoma genes and phenotypes: Focus on FOXC1 mutations causing anterior segment dysgenesis and hearing loss},
	journal = {Exp Eye Res},
	volume = {190},
	year = {2020},
	month = {2020 Jan},
	pages = {107893},
	abstract = {Childhood glaucoma is an important cause of blindness world-wide. Eleven genes are currently known to cause inherited forms of glaucoma with onset before age 20. While all the early-onset glaucoma genes cause severe disease, considerable phenotypic variability is observed among mutations carriers. In particular, FOXC1 genetic variants are associated with a broad range of phenotypes including multiple forms of glaucoma and also systemic abnormalities, especially hearing loss. FOXC1 is a member of the forkhead family of transcription factors and is involved in neural crest development necessary for formation of anterior eye structures and also pharyngeal arches that form the middle ear bones. In this study we review the clinical phenotypes reported for known FOXC1 mutations and show that mutations in patients with reported ocular anterior segment abnormalities and hearing loss primarily disrupt the critically important forkhead domain. These results suggest that optimal care for patients affected with anterior segment dysgenesis should include screening for FOXC1 mutations and also testing for hearing loss.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.107893},
	author = {Gauthier, Angela C and Wiggs, Janey L}
}
@article {1532376,
	title = {When gold standards change: time to move on from Goldmann tonometry?},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {1-2},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-317112},
	author = {Gazzard, Gus and Jayaram, Hari and Roldan, Ana M and Friedman, David S}
}
@article {1504055,
	title = {Juvenile cataract in association with tuberous sclerosis complex},
	journal = {Ophthalmic Genet},
	volume = {41},
	number = {4},
	year = {2020},
	month = {2020 Aug},
	pages = {345-349},
	abstract = {BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas occurring in multiple organ systems including the brain, kidneys, heart, lungs, liver, skin, and the eyes. Typical retinal findings associated with TSC include astrocytic hamartoma and achromic patch. While rare cases of cataract occurring in the setting of TSC have been reported, this is the first analysis of a large series of individuals with TSC that aims to quantify the frequency of this finding and to describe its clinical and genetic associations. MATERIALS AND METHODS: This is a retrospective chart review of 244 patients from the Herscot Center for Tuberous Sclerosis Complex at the Massachusetts General Hospital who underwent complete ophthalmic examination. We describe the clinical and genetic findings in five individuals with TSC and juvenile cataract. RESULTS: Four of five cases (80\%) were unilateral. The cataract was described as having an anterior subcapsular component in 3 of 5 cases (60\%). Three individuals (60\%) underwent lensectomy with intraocular lens (IOL) implant and two individuals (40\%) were observed. Genetic testing revealed a known disease-causing mutation in in 100\% of cases. CONCLUSIONS: Recent evidence suggests that mTOR signaling may play a role in cataract formation which could explain the relatively high incidence of juvenile cataract in this population. Juvenile cataract is a potentially under-recognized ocular manifestation of TSC.},
	issn = {1744-5094},
	doi = {10.1080/13816810.2020.1755989},
	author = {Geffrey, A L and Geenen, K R and Abati, E and Greenstein, S H and VanderVeen, D K and Levy, R L and Davidson, S L and McGarrey, M P and Thiele, E A and Aronow, M E}
}
@article {1615202,
	title = {Traumatic Hyphema},
	journal = {J Emerg Med},
	volume = {61},
	number = {6},
	year = {2021},
	month = {2021 Dec},
	pages = {740-741},
	issn = {0736-4679},
	doi = {10.1016/j.jemermed.2021.07.041},
	author = {Genadry, Katia C and Shrock, Christine and O{\textquoteright}Shea, Delia and Vatsa, Rajet and Shah, Ankoor S and Gise, Ryan and Lipsett, Susan C}
}
@article {1593866,
	title = {Perspectives for preclinical mouse models of glaucoma after Boston keratoprosthesis type 1},
	journal = {Exp Eye Res},
	volume = {208},
	year = {2021},
	month = {2021 Jul},
	pages = {108615},
	abstract = {Animal models of the Boston keratoprosthesis type 1 (KPro) are needed to study glaucoma damage after KPro implantation to control for confounding comorbidities common in human KPro recipients. The purpose of this study was to determine the feasibility of establishing a reproducible mouse model of glaucoma after KPro surgery, specifically that of a miniaturized mouse model of KPro (mKPro). In the present study, a total of 20 corneas of donor C57BL/6 mice (n\&nbsp;=\&nbsp;10) were implanted in one eye of each recipient BALB/C mouse (n\&nbsp;=\&nbsp;20), assembled as part of the mKPro, either with or without intraoperative lensectomy. Main feasibility outcomes consisted in incidence rates of loss of tone, capsule nicking, and lens extrusion, as well as acquisition of posterior segment optical coherence tomography (OCT) images. With lensectomy (n\&nbsp;=\&nbsp;10), loss of ocular tone and retinal detachment occurred in 100\% of mice. Without lensectomy (n\&nbsp;=\&nbsp;10), capsule nicking and opening, as well as lens extrusion, occurred in 80\% of mice. Causes of these complications included the large proportion of intraocular volume occupied by the lens, the shallow anterior chamber, and thus the lack of available intraocular volume to implant the KPro if the lens remains present. Successful mouse KPro surgery may require a great deal of practice to be useful as a reproducible model. Animal KPro models ought to be pursued further by research teams in future studies.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2021.108615},
	author = {Geoffrion, Dominique and Robert, Marie-Claude and Chodosh, James and Di Polo, Adriana and Harissi-Dagher, Mona}
}
@article {1667713,
	title = {Correspondence},
	journal = {Retina},
	volume = {43},
	number = {5},
	year = {2023},
	month = {2023 May 01},
	pages = {e30-e31},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003758},
	author = {Geoffrion, Dominique and Melki, Samir and Harissi-Dagher, Mona}
}
@article {1517199,
	title = {TWO-YEAR RESULTS OF INTRAVITREAL INJECTIONS OF AFLIBERCEPT IN COATS DISEASE: A CASE REPORT},
	journal = {Retin Cases Brief Rep},
	volume = {16},
	number = {4},
	year = {2022},
	month = {2022 Jul 01},
	pages = {473-478},
	abstract = {PURPOSE: To report long-term results of treatment with intravitreal injections of aflibercept in a newly diagnosed case of Coats disease. METHODS: An 18-year-old man presented to the retina clinic of our hospital complaining of blurred vision in the right eye for the past 3 months. His past medical and ocular history were unremarkable. The best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left eye. Fundoscopy in the right eye revealed extensive macular edema with a circinate ring of hard exudates in the posterior pole temporally to the macula. Optical coherence tomography demonstrated macular edema with subretinal fluid. Peripheral telangiectasias and light bulb aneurysms in the inferior temporal arcade as well as in the nasal far periphery were found in the right eye in fluorescein angiography, confirming the diagnosis of stage 2B Coats disease. The left eye was normal. RESULTS: The original therapeutic strategy proposed was antivascular endothelial growth factor injections in the right eye, followed by laser photocoagulation. However, the patient did not consent to laser treatment and was treated with aflibercept monotherapy with 8 monthly intravitreal injections of aflibercept, followed by 6 injections every 2 months for a total of 14 injections over a period of 2 years. The best-corrected visual acuity in the right eye improved to 20/25 while optical coherence tomography imaging revealed significant decrease in retinal thickness with resolution of macular edema, and fluorescein angiography demonstrated prominent regression of aneurysms and leakage. CONCLUSION: To the best of our knowledge, this is the first case treated with aflibercept monotherapy, suggesting the significant role of vascular endothelial growth factor in vascular permeability in Coats and supporting the rationale that antivascular endothelial growth factors are a valuable therapeutic option for Coats disease.},
	keywords = {Adolescent, Angiogenesis Inhibitors, Humans, Intravitreal Injections, Macular Edema, Male, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins, Retinal Telangiectasis, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001011},
	author = {Georgakopoulos, Constantinos D and Tsapardoni, Foteini N and Makri, Olga E and Vavvas, Demetrios}
}
@article {1559532,
	title = {KCNV2-associated Retinopathy: Genetics, Electrophysiology and Clinical Course - KCNV2 Study Group Report 1},
	journal = {Am J Ophthalmol},
	year = {2020},
	month = {2020 Dec 10},
	abstract = {PURPOSE: To investigate genetics, electrophysiology and clinical course of KCNV2-associated retinopathy in a cohort of children and adults. STUDY DESIGN: Multicenter international clinical cohort study. METHODS: Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) incorporating the international standards were reviewed and quantified and compared with age and recordings from control subjects. RESULTS: In total 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before the age of 12 years (age range: 0-11 years). Decreased visual acuity was present in all patients, and four other symptoms were common: reduced color vision (78.6\%), photophobia (53.5\%), nyctalopia (43.6\%), and nystagmus (38.6\%). After a mean follow of 8.4 years, the mean best corrected visual acuity (BCVA, {\textpm}SD) decreased from 0.81 LogMAR (0.27 LogMAR) to 0.90 LogMAR (0.31 LogMAR). Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the DA 0.01 ERG, DA 10 ERG a-wave, LA30Hz and LA3 ERG b-wave were 55\%, 21\%, 48\% and 74\% respectively. Peak times showed stability across 6 decades. CONCLUSION: In KCNV2-retinopathy full-field ERGs are diagnostic, and consistent with largely stable peripheral retinal dysfunction. Report No.1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.11.022},
	author = {Georgiou, Michalis and Robson, Anthony G and Fujinami, Kaoru and Leo, Shaun Michael and Vincent, Ajoy and Nasser, Fadi and Cabral De Guimar{\~a}es, Thales Ant{\^o}nio and Khateb, Samer and Pontikos, Nikolas and Fujinami-Yokokawa, Yu and Liu, Xiao and Tsunoda, Kazushige and Hayashi, Takaaki and Vargas, Mauricio E and Thiadens, Alberta A H J and de Carvalho, Emanuel R and Nguyen, Xuan-Thanh-An and Arno, Gavin and Mahroo, Omar A and Martin-Merida, Maria Inmaculada and Jimenez-Rolando, Belen and Gordo, Gema and Carre{\~n}o, Ester and Carmen, Ayuso and Sharon, Dror and Kohl, Susanne and Huckfeldt, Rachel M and Wissinger, Bernd and Boon, Camiel J F and Banin, Eyal and Pennesi, Mark E and Khan, Arif O and Webster, Andrew R and Zrenner, Eberhart and H{\'e}on, Elise and Michaelides, Michel}
}
@article {1586168,
	title = {KCNV2-associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints - KCNV2 Study Group Report 2},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 Mar 15},
	abstract = {PURPOSE: To describe the detailed retinal phenotype of\&nbsp;KCNV2-associated\&nbsp;retinopathy. STUDY DESIGN: Multicenter international retrospective case series. METHODS: Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses. RESULTS: Three distinct macular FAF features were identified: i) centrally increased signal (n=35, 41.7\%), ii) DAF (n=27, 31.1\%), and iii) ring of increased signal (n=37, 44.0\%). Five distinct FAF groups were identified based on combinations of those characteristics, with 23.5\% of patients changing FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into five grades: (i) continuous EZ (20.5\%), (ii) EZ disruption (26.1\%), (iii) EZ absence, without optical gap and with preserved retinal pigment epithelium (RPE) complex (21.6\%); iv) loss of EZ and an hyporeflective zone at the foveola (6.8\%); and (v) outer retina and RPE complex loss (25.0\%). Eighty-six patients had scans available from both eyes, with 83 (96.5\%) having the same grade in both eyes, and 36.1\% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of ONL thickness change was similar for right and left eyes. CONCLUSION: KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging; although ONL thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.03.004},
	author = {Georgiou, Michalis and Fujinami, Kaoru and Vincent, Ajoy and Nasser, Fadi and Khateb, Samer and Vargas, Mauricio E and Thiadens, Alberta A H J and de Carvalho, Emanuel R and Nguyen, Xuan-Thanh-An and Cabral De Guimar{\~a}es, Thales Ant{\^o}nio and Robson, Anthony G and Mahroo, Omar A and Pontikos, Nikolas and Arno, Gavin and Fujinami-Yokokawa, Yu and Leo, Shaun Michael and Liu, Xiao and Tsunoda, Kazushige and Hayashi, Takaaki and Jimenez-Rolando, Belen and Martin-Merida, Maria Inmaculada and Avila-Fernandez, Almudena and Carre{\~n}o, Ester and Garcia-Sandoval, Blanca and Carmen, Ayuso and Sharon, Dror and Kohl, Susanne and Huckfeldt, Rachel M and Boon, Camiel J F and Banin, Eyal and Pennesi, Mark E and Wissinger, Bernd and Webster, Andrew R and H{\'e}on, Elise and Khan, Arif O and Zrenner, Eberhart and Michaelides, Michel}
}
@article {1580509,
	title = {Potential of Application of Iron Chelating Agents in Ophthalmic Diseases},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {157-161},
	abstract = {The investigations discussed in this review indicate that iron may exacerbate different eye diseases. Therefore, it is plausible that reducing cellular or body iron stores could influence disease pathogenesis, so it is logical to consider the iron chelators{\textquoteright} potential protective role in the various ophthalmic diseases in the form of topical eye drops or slow releasing injectable compounds as an adjuvant treatment.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1887900},
	author = {Ghaffarieh, Alireza and Ciolino, Joseph B}
}
@article {280911,
	title = {Lower Eyelid Involutional Ectropion Repair With Lateral Tarsal Strip and Internal Retractor Reattachment With Full-Thickness Eyelid Sutures.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {30},
	number = {5},
	year = {2014},
	month = {2014 September/O},
	pages = {424-426},
	abstract = {PURPOSE: To report a novel surgical technique for lower eyelid involutional ectropion repair using a lateral tarsal strip and internal retractor reattachment procedure involving full-thickness eyelid sutures. METHODS:: A retrospective review was performed of patients who underwent repair of involutional ectropion via lateral tarsal strip and internal retractor reattachment with full-thickness eyelid sutures by 1 surgeon. Patients having concomitant or previous eyelid surgical procedures were excluded. Collected data included patient demographics, surgical outcomes, and length of follow up. RESULTS:: Forty-one lower eyelids of 31 patients with involutional ectropion underwent surgical repair. There were 17 men and 14 women in the age range of 69 to 92 years (mean age 82.2 {\textpm} 5.9 years). Surgical sites included 22 right and 19 left lower eyelids. Follow up ranged from 1 to 48 months with an average of 5.9 months. Surgical success with anatomical correction of involutional ectropion was achieved in 39 of 41 eyelids (95.1\%). There were no perioperative or postoperative complications. Two of 41 (4.9\%) eyelids had recurrence of ectropion 7 and 18 months after the procedure. CONCLUSIONS:: This procedure combining lateral tarsal strip with internal retractor reattachment involving full-thickness eyelid sutures effectively addresses horizontal eyelid laxity and tarsal instability, providing an effective technique to correct involutional ectropion of the lower eyelid.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000218},
	author = {Ghafouri, Roya H and Allard, Felicia D and Migliori, Michael E and Freitag, Suzanne K}
}
@article {1782321,
	title = {Genome-wide risk prediction of primary open-angle glaucoma across multiple ancestries},
	journal = {medRxiv},
	year = {2023},
	month = {2023 Nov 08},
	abstract = {BACKGROUND: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The disease is often only diagnosed after retinal ganglion cell damage has occurred, with current treatments unable to restore lost vision. Developing risk identification tools for POAG will help enable timely diagnosis and prevent irreparable damage from occurring, especially for ancestry groups (such as African (AFR)) where the disease prevalence is high. Given the heritable nature of POAG, we aim to develop a polygenic score (PGS), which could facilitate earlier POAG risk detection for timely prevention and diagnosis. METHODS: We applied a multi-ancestry multi-trait approach to build powerful PGS for POAG. We first integrated the new and existing genetics data on POAG and two key endophenotypes, intraocular pressure (IOP) and vertical cup-to-disc ratio (VCDR). We then leveraged the shared POAG genetic information across European (EUR), AFR and Asian ancestries and between POAG and each of IOP and VCDR to develop PGS for POAG risk prediction. We systematically assessed the PGS prediction power and risk stratification ability in POAG cohorts of different ancestries. RESULTS: Our newly developed PGS showed improved accuracy compared to previous PGS for POAG risk prediction in EUR ancestry. We showed the transferability of PGS based on EUR ancestry in the prediction of POAG status in AFR and Asian ancestries. Utilizing the shared genetic information across ancestries further improved PGS prediction power for POAG in AFR and East Asian (EAS). For individuals with South Asian ancestry, those in the top PGS decile were diagnosed ~18 years earlier than those in the bottom decile. For AFR ancestry, individuals in the top percentile had an odds ratio of 4.08 (95\% CI: 2.33-7.45) compared with the remainder of the population using the newly developed AFR-specific PGS. CONCLUSIONS: In the current study, we developed PGS for POAG risk prediction in EUR, Asian and AFR populations. These PGS, to our best knowledge, are the most powerful PGS currently for POAG risk screening and stratification. We believe that our study will lead to improved POAG detection across diverse populations in the future by enabling targeting clinical screening of people at high levels of genetic risk.},
	doi = {10.1101/2023.11.08.23298255},
	author = {Gharahkhani, Puya and He, Weixiong and Han, Xikun and Ong, Jue Sheng and Renter{\'\i}a, Miguel E and Wiggs, Janey L and Khawaja, Anthony P and Trzaskowski, Maciej and Mackey, David A and Craig, Jamie E and Hewitt, Alex W and IGGC International Glaucoma Genetics Consortium and Macgregor, Stuart and Wu, Yeda}
}
@article {1302181,
	title = {Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Feb 15},
	pages = {3124},
	abstract = {Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-20435-9},
	author = {Gharahkhani, Puya and Burdon, Kathryn P and Cooke Bailey, Jessica N and Hewitt, Alex W and Law, Matthew H and Pasquale, Louis R and Kang, Jae H and Haines, Jonathan L and Souzeau, Emmanuelle and Zhou, Tiger and Siggs, Owen M and Landers, John and Awadalla, Mona and Sharma, Shiwani and Mills, Richard A and Ridge, Bronwyn and Lynn, David and Casson, Robert and Graham, Stuart L and Goldberg, Ivan and White, Andrew and Healey, Paul R and Grigg, John and Lawlor, Mitchell and Mitchell, Paul and Ruddle, Jonathan and Coote, Michael and Walland, Mark and Best, Stephen and Vincent, Andrea and Gale, Jesse and RadfordSmith, Graham and Whiteman, David C and Montgomery, Grant W and Martin, Nicholas G and Mackey, David A and Wiggs, Janey L and Macgregor, Stuart and Craig, Jamie E and NEIGHBORHOOD Consortium}
}
@article {1580508,
	title = {Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries},
	journal = {Nat Commun},
	volume = {12},
	number = {1},
	year = {2021},
	month = {2021 02 24},
	pages = {1258},
	abstract = {Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.},
	issn = {2041-1723},
	doi = {10.1038/s41467-020-20851-4},
	author = {Gharahkhani, Puya and Jorgenson, Eric and Hysi, Pirro and Khawaja, Anthony P and Pendergrass, Sarah and Han, Xikun and Ong, Jue Sheng and Hewitt, Alex W and Segr{\`e}, Ayellet V and Rouhana, John M and Hamel, Andrew R and Igo, Robert P and Choquet, Helene and Qassim, Ayub and Josyula, Navya S and Cooke Bailey, Jessica N and Bonnemaijer, Pieter W M and Iglesias, Adriana and Siggs, Owen M and Young, Terri L and Vitart, Veronique and Thiadens, Alberta A H J and Karjalainen, Juha and Uebe, Steffen and Melles, Ronald B and Nair, K Saidas and Luben, Robert and Simcoe, Mark and Amersinghe, Nishani and Cree, Angela J and Hohn, Rene and Poplawski, Alicia and Chen, Li Jia and Rong, Shi-Song and Aung, Tin and Vithana, Eranga Nishanthie and NEIGHBORHOOD Consortium and ANZRAG Consortium and BioBank Japan Project and FinnGen study and UK Biobank Eye and Vision Consortium and GIGA Study Group and 23andMe Research Team and Tamiya, Gen and Shiga, Yukihiro and Yamamoto, Masayuki and Nakazawa, Toru and Currant, Hannah and Birney, Ewan and Wang, Xin and Auton, Adam and Lupton, Michelle K and Martin, Nicholas G and Ashaye, Adeyinka and Olawoye, Olusola and Williams, Susan E and Akafo, Stephen and Ramsay, Michele and Hashimoto, Kazuki and Kamatani, Yoichiro and Akiyama, Masato and Momozawa, Yukihide and Foster, Paul J and Khaw, Peng T and Morgan, James E and Strouthidis, Nicholas G and Kraft, Peter and Kang, Jae H and Pang, Chi Pui and Pasutto, Francesca and Mitchell, Paul and Lotery, Andrew J and Palotie, Aarno and van Duijn, Cornelia and Haines, Jonathan L and Hammond, Chris and Pasquale, Louis R and Klaver, Caroline C W and Hauser, Michael and Khor, Chiea Chuen and Mackey, David A and Kubo, Michiaki and Cheng, Ching-Yu and Craig, Jamie E and Macgregor, Stuart and Wiggs, Janey L}
}
@article {303911,
	title = {Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.},
	journal = {Nat Genet},
	volume = {46},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {1120-5},
	abstract = {Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 {\texttimes} 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 {\texttimes} 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 {\texttimes} 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.},
	issn = {1546-1718},
	doi = {10.1038/ng.3079},
	author = {Gharahkhani, Puya and Burdon, Kathryn P and Fogarty, Rhys and Sharma, Shiwani and Hewitt, Alex W and Martin, Sarah and Law, Matthew H and Cremin, Katie and Bailey, Jessica N Cooke and Loomis, Stephanie J and Pasquale, Louis R and Haines, Jonathan L and Hauser, Michael A and Viswanathan, Ananth C and McGuffin, Peter and Topouzis, Fotis and Foster, Paul J and Graham, Stuart L and Casson, Robert J and Chehade, Mark and White, Andrew J and Zhou, Tiger and Souzeau, Emmanuelle and Landers, John and Fitzgerald, Jude T and Klebe, Sonja and Ruddle, Jonathan B and Goldberg, Ivan and Healey, Paul R and Wellcome Trust Case Control Consortium 2 and NEIGHBORHOOD Consortium and Mills, Richard A and Wang, Jie Jin and Montgomery, Grant W and Martin, Nicholas G and Radford-Smith, Graham and Whiteman, David C and Brown, Matthew A and Wiggs, Janey L and Mackey, David A and Mitchell, Paul and Macgregor, Stuart and Craig, Jamie E}
}
@article {1586152,
	title = {Advanced nanodelivery platforms for topical ophthalmic drug delivery},
	journal = {Drug Discov Today},
	volume = {26},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {1437-1449},
	abstract = {Conventional eye drops have several limitations, including the need for multiple applications per dose, hourly based dosage regiments, and suboptimal ocular bioavailability (\&lt;5\%). The efficacy of topical ophthalmic medications can be significantly improved by controlling their contact time with the adherent mucin layer and by inducing sustained release properties, thus allowing for a prolonged contact time of the drug with the ocular tissues, which eventually will lead to improved drug bioavailability and a significant decrease in the frequency of eyedrop instillation. In this review, we critically highlight recent and innovative nanodrug delivery platforms, with a primary focus on the integration of nanotechnology, biomaterials, and polymer chemistry to facilitate precise spatial and temporal control over sustained drug release to the cornea.},
	issn = {1878-5832},
	doi = {10.1016/j.drudis.2021.02.027},
	author = {Gholizadeh, Shima and Wang, Ziqing and Chen, Xi and Dana, Reza and Annabi, Nasim}
}
@article {1658673,
	title = {Development and optimization of an ocular hydrogel adhesive patch using definitive screening design (DSD)},
	journal = {Biomater Sci},
	volume = {11},
	number = {4},
	year = {2023},
	month = {2023 Feb 14},
	pages = {1318-1334},
	abstract = {Adhesive hydrogels based on chemically modified photocrosslinkable polymers with specific physicochemical properties are frequently utilized for sealing wounds or incisions. These adhesive hydrogels offer tunable characteristics such as tailorable tissue adhesion, mechanical properties, swelling ratios, and enzymatic degradability. In this study, we developed and optimized a photocrosslinkable adhesive patch, GelPatch, with high burst pressure, minimal swelling, and specific mechanical properties for application as an ocular (sclera and subconjunctival) tissue adhesive. To achieve this, we formulated a series of hydrogel patches composed of different polymers with various levels of methacrylation, molecular weights, and hydrophobic/hydrophilic properties. A computerized multifactorial definitive screening design (DSD) analysis was performed to identify the most prominent components impacting critical response parameters such as adhesion, swelling ratio, elastic modulus, and second order interactions between applied components. These parameters were mathematically processed to generate a predictive model that identifies the linear and non-linear correlations between these factors. In conclusion, an optimized formulation of GelPatch was selected based on two modified polymers: gelatin methacryloyl (GelMA) and glycidyl methacrylated hyaluronic acid (HAGM). The ex vivo results confirmed adhesion and retention of the optimized hydrogel subconjunctivally and on the sclera for up to 4 days. The developed formulation has potential to be used as an ocular sealant for quick repair of laceration type ocular injuries.},
	keywords = {Adhesives, Elastic Modulus, Gelatin, Hydrogels, Methacrylates, Polymers, Tissue Adhesives},
	issn = {2047-4849},
	doi = {10.1039/d2bm01013e},
	author = {Gholizadeh, Shima and Chen, Xi and Yung, Ann and Naderi, Amirreza and Ghovvati, Mahsa and Liu, Yangcheng and Farzad, Ashkan and Mostafavi, Azadeh and Dana, Reza and Annabi, Nasim}
}
@article {1667722,
	title = {Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons},
	journal = {J Neurophysiol},
	volume = {129},
	number = {3},
	year = {2023},
	month = {2023 Mar 01},
	pages = {609-618},
	abstract = {Despite extensive study, the mechanisms underlying pain after axonal injury remain incompletely understood. Pain after corneal refractive surgery provides a model, in humans, of the effect of injury to trigeminal afferent nerves. Axons of trigeminal ganglion neurons that innervate the cornea are transected by laser-assisted in situ keratomileusis (LASIK). Although most patients do not experience postoperative pain, a small subgroup develop persistent ocular pain. We previously carried out genomic analysis and determined that some patients with persistent pain after axotomy of corneal axons during refractive surgery carry mutations in genes that encode the electrogenisome of trigeminal ganglion neurons, the ensemble of ion channels and receptors that regulate excitability within these cells, including SCN9A, which encodes sodium channel Nav1.7, a threshold channel abundantly expressed in sensory neurons that has been implicated in a number of pain-related disorders. Here, we describe the biophysical and electrophysiological profiling of the P610T Nav1.7 mutation found in two male siblings with persistent ocular pain after refractive surgery. Our results indicate that this mutation impairs the slow inactivation of Nav1.7. As expected from this proexcitatory change in channel function, we also demonstrate that this mutation produces increased spontaneous activity in trigeminal ganglion neurons. These findings suggest that this gain-of-function mutation in Nav1.7 may contribute to pain after injury to the axons of trigeminal ganglion neurons.NEW \&amp; NOTEWORTHY Mechanisms underlying pain after axonal injury remain elusive. A small subgroup of patients experience pain after corneal refractive surgery, providing a human pain model after well-defined injury to axons. Here we analyze a mutation (P610T) in Nav1.7, a threshold sodium channel expressed in nociceptors, found in two siblings with persistent ocular pain after refractive surgery. We show that it impairs channel slow inactivation, thereby triggering inappropriate repetitive activity in trigeminal ganglion axons that signal eye pain.},
	keywords = {Axons, Cornea, Eye Pain, Ganglia, Spinal, Humans, Male, Mutation, NAV1.7 Voltage-Gated Sodium Channel, Neurons, Pain, Siblings},
	issn = {1522-1598},
	doi = {10.1152/jn.00457.2022},
	author = {Ghovanloo, Mohammad-Reza and Effraim, Philip R and Yuan, Jun-Hui and Schulman, Betsy R and Jacobs, Deborah S and Dib-Hajj, Sulayman D and Waxman, Stephen G}
}
@article {836836,
	title = {Persistent Blurry Vision After a Routine Eye Examination.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {9},
	year = {2016},
	month = {2016 Sep 1},
	pages = {1065-6},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.0812},
	author = {Gilbert, Aubrey L and Thanos, Aristomenis and Pineda, Roberto}
}
@article {931061,
	title = {Evaluation and Management of Acute Acquired Comitant Esotropia in Children.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	month = {2017},
	pages = {8-13},
	abstract = {Acute acquired comitant esotropia (AACE) is characterized by a sudden-onset eye misalignment with an equal angle of deviation in all fields of gaze. This form of esotropia is distinct from common forms of childhood esotropia, such as infantile esotropia and accommodative esotropia, in the rapid tempo and typically later timing of onset; further, AACE is distinct from restrictive or paretic strabismus, which usually results in an incomitant angle of deviation that varies with the direction of gaze. The underlying etiologies for AACE are broad but, in some cases, it may be associated with significant neurologic disease. Therefore, the purpose of this article is to examine and summarize the current literature on AACE to provide a framework for the evaluation and management of this form of acquired strabismus.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228398},
	author = {Gilbert, Aubrey L and Koo, Euna B and Heidary, Gena}
}
@article {961696,
	title = {Duane syndrome with prominent oculo-auricular phenomenon},
	journal = {J AAPOS},
	volume = {21},
	number = {2},
	year = {2017},
	month = {2017 Apr},
	pages = {165-167},
	abstract = {Duane syndrome is a congenital cranial dysinnervation disorder involving absent or anomalous innervation of the lateral and medial rectus muscles that is sometimes associated with other manifestations of dysinnervation. We describe a patient with right esotropic Duane syndrome with a long-standing retroauricular tugging sensation in right gaze who was noted to have prominent ipsilateral oculo-auricular phenomenon, representing either abnormal enhancement of existing innervation or an uncommon dysinnervation. After successful strabismus surgery the tugging sensation improved but the phenomenon could still be elicited.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2016.09.017},
	author = {Gilbert, Aubrey L and Hunter, David G}
}
@article {882926,
	title = {Update on the evaluation of pediatric idiopathic intracranial hypertension.},
	journal = {Curr Opin Ophthalmol},
	year = {2016},
	month = {2016 Aug 31},
	abstract = {PURPOSE OF REVIEW: Papilledema associated with idiopathic intracranial hypertension (IIH) may result in irreversible, progressive visual loss. The development of tools for the evaluation of pediatric patients with IIH is particularly relevant as many patients may not be able to comply with the detailed clinical evaluation utilized in adults for the treatment and management of this disease. The purpose of this review is to summarize relevant articles on the diagnostic tools used in evaluation and management of pediatric IIH. RECENT FINDINGS: Studies suggest that characteristic pediatric IIH MRI findings include empty sella turcica, decreased pituitary gland size, optic nerve tortuosity, perioptic subarachnoid space enlargement, posterior globe flattering, and intraocular protrusion of the optic nerve head. On optical coherence tomography (OCT), increased retinal nerve fiber layer and macular thickness may be observed in children with IIH compared with controls. The retinal nerve fiber layer thickness seems to coincide with the severity of papilledema and may be more sensitive than funduscopy for detecting optic nerve head elevation. Research on ultrasound of the optic nerve shows increased size of the optic nerve sheath diameter in pediatric IIH patients, and this may correlate with increased opening pressure on lumbar puncture. SUMMARY: There appears to be characteristic findings on MRI, OCT, and ultrasound studies in pediatric IIH patients. Although ultrasound is rarely used for monitoring these patients nowadays, MRI and OCT can be useful in the evaluation and management of these individuals.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000317},
	author = {Gilbert, Aubrey L and Heidary, Gena}
}
@article {1354336,
	title = {A comparison of retrokeratoprosthetic membrane and conjunctival inflammatory responses to silicone oil},
	journal = {J Ophthalmic Inflamm Infect},
	volume = {4},
	year = {2014},
	month = {2014},
	pages = {15},
	abstract = {Silicone oil continues to be an important aid in retinal detachment surgery. We report a case in which disparate responses to silicone oil were noted in the conjunctiva and intraocularly. Intraocularly, the oil permeated a fibrous membrane that formed behind a keratoprosthesis, the first example of this phenomenon. We detail the histological response to the oil at this site as well as a distinctly different reaction present to oil in the conjunctiva of the same eye. The divergence of histological responses provides a demonstration of the eye{\textquoteright}s apparent retained capacity to protect against intraocular inflammation, despite multiple previous surgeries.},
	issn = {1869-5760},
	doi = {10.1186/s12348-014-0015-y},
	author = {Gilbert, Aubrey L and Jakobiec, Frederick A and Chodosh, James and Eliott, Dean}
}
@article {1549025,
	title = {Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of Enterococcus faecalis},
	journal = {mBio},
	volume = {11},
	number = {6},
	year = {2020},
	month = {2020 Nov 24},
	abstract = {The enterococci, which are among the leading causes of multidrug-resistant (MDR) hospital infection, are notable for their environmental ruggedness, which extends to intrinsic antibiotic resistance. To identify genes that confer this unique property, we used Tn-seq to comprehensively explore the genome of MDR strain MMH594 for genes important for growth in nutrient-containing medium and with low-level antibiotic challenge. As expected, a large core of genes for DNA replication, expression, and central metabolism, shared with other bacteria, are intolerant to transposon disruption. However, genes were identified that are important to that are either absent from or unimportant for and fitness when similarly tested. Further, 217 genes were identified that when challenged by sub-MIC antibiotic levels exhibited reduced tolerance to transposon disruption, including those previously shown to contribute to intrinsic resistance, and others not previously ascribed this role. is one of the few Gram-positive bacteria experimentally shown to possess a functional Entner-Doudoroff pathway for carbon metabolism, a pathway that contributes to stress tolerance in other microbes. Through functional genomics and network analysis we defined the unusual structure of this pathway in and assessed its importance. These approaches also identified toxin-antitoxin and related systems that are unique and active in Finally, we identified genes that are absent in the closest nonenterococcal relatives, the vagococci, and that contribute importantly to fitness with and without antibiotic selection, advancing an understanding of the unique biology of enterococci. Enterococci are leading causes of antibiotic-resistant infection transmitted in hospitals. The intrinsic hardiness of these organisms allows them to survive disinfection practices and then proliferate in the gastrointestinal tracts of antibiotic-treated patients. The objective of this study was to identify the underlying genetic basis for its unusual hardiness. Using a functional genomic approach, we identified traits and pathways of general importance for enterococcal survival and growth that distinguish them from closely related pathogens as well as ancestrally related species. We further identified unique traits that enable them to survive antibiotic challenge, revealing a large set of genes that contribute to intrinsic antibiotic resistance and a smaller set of uniquely important genes that are rare outside enterococci.},
	issn = {2150-7511},
	doi = {10.1128/mBio.02962-20},
	author = {Gilmore, Michael S and Salamzade, Rauf and Selleck, Elizabeth and Bryan, Noelle and Mello, Suelen S and Manson, Abigail L and Earl, Ashlee M}
}
@article {1363280,
	title = {Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era},
	journal = {Curr Opin Microbiol},
	volume = {16},
	number = {1},
	year = {2013},
	month = {2013 Feb},
	pages = {10-6},
	abstract = {The enterococci evolved over eons as highly adapted members of gastrointestinal consortia of a wide variety of hosts, but for reasons that are not entirely clear, emerged in the 1970s as leading causes of multidrug resistant hospital infection. Hospital-adapted pathogenic isolates are characterized by the presence of multiple mobile elements conferring antibiotic resistance, as well as pathogenicity islands, capsule loci and other variable traits. Enterococci may have been primed to emerge among the vanguard of antibiotic resistant strains because of their occurrence in the GI tracts of insects and simple organisms living and feeding on organic matter that is colonized by antibiotic resistant, antibiotic producing micro-organisms. In response to the opportunity to inhabit a new niche--the antibiotic treated hospital patient--the enterococcal genome is evolving in a pattern characteristic of other bacteria that have emerged as pathogens because of opportunities stemming from anthropogenic change.},
	keywords = {Anti-Bacterial Agents, Carrier State, Cross Infection, Drug Resistance, Multiple, Bacterial, Enterococcus, Evolution, Molecular, Gastrointestinal Tract, Gene Transfer, Horizontal, Gram-Positive Bacterial Infections, Humans, Interspersed Repetitive Sequences, Virulence Factors},
	issn = {1879-0364},
	doi = {10.1016/j.mib.2013.01.006},
	author = {Gilmore, Michael S and Lebreton, Francois and van Schaik, Willem}
}
@article {1460358,
	title = {The CRISPR-Antibiotic Resistance Connection},
	journal = {CRISPR J},
	volume = {2},
	year = {2019},
	month = {2019 Aug},
	pages = {199-200},
	issn = {2573-1602},
	doi = {10.1089/crispr.2019.29065.msg},
	author = {Gilmore, Michael S}
}
@article {1363281,
	title = {Dual defensin strategy for targeting Enterococcus faecalis},
	journal = {Proc Natl Acad Sci U S A},
	volume = {110},
	number = {50},
	year = {2013},
	month = {2013 Dec 10},
	pages = {19980-1},
	keywords = {Adenosine Triphosphatases, Aminoacyltransferases, Bacterial Proteins, beta-Defensins, Cysteine Endopeptidases, Enterococcus faecalis, Humans, Membrane Transport Proteins, SEC Translocation Channels, Virulence Factors},
	issn = {1091-6490},
	doi = {10.1073/pnas.1319939110},
	author = {Gilmore, Michael S and Lebreton, Francois and Van Tyne, Daria}
}
@article {439606,
	title = {Pheromone killing of multidrug-resistant Enterococcus faecalis V583 by native commensal strains.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {112},
	number = {23},
	year = {2015},
	month = {2015 Jun 9},
	pages = {7273-8},
	abstract = {Multidrug-resistant Enterococcus faecalis possess numerous mobile elements that encode virulence and antibiotic resistance traits as well as new metabolic pathways, often constituting over one-quarter of the genome. It was of interest to determine how this large accretion of mobile elements affects competitive growth in the gastrointestinal (GI) tract consortium. We unexpectedly observed that the prototype clinical isolate strain V583 was actively killed by GI tract flora, whereas commensal enterococci flourished. It was found that killing of V583 resulted from lethal cross-talk between accumulated mobile elements and that this cross-talk was induced by a heptapeptide pheromone produced by native E. faecalis present in the fecal consortium. These results highlight two important aspects of the evolution of multidrug-resistant enterococci: (i) the accretion of mobile elements in E. faecalis V583 renders it incompatible with commensal strains, and (ii) because of this incompatibility, multidrug-resistant strains sharing features found in V583 cannot coexist with commensal strains. The accumulation of mobile elements in hospital isolates of enterococci can include those that are inherently incompatible with native flora, highlighting the importance of maintaining commensal populations as means of preventing colonization and subsequent infection by multidrug-resistant strains.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1500553112},
	author = {Gilmore, Michael S and Rauch, Marcus and Ramsey, Matthew M and Himes, Paul R and Varahan, Sriram and Manson, Janet M and Lebreton, Francois and Hancock, Lynn Ernest}
}
@article {303891,
	title = {Orbital emphysema complicating jones tube placement in a patient treated with continuous positive airway pressure.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {1},
	year = {2015},
	month = {2015 Jan-Feb},
	pages = {e25},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000299},
	author = {Ginat, Daniel Thomas and Freitag, Suzanne K}
}
@article {630186,
	title = {Lacrimal gland abscess presenting with preseptal cellulitis depicted on CT.},
	journal = {J Ophthalmic Inflamm Infect},
	volume = {6},
	number = {1},
	year = {2016},
	month = {2016 Dec},
	pages = {1},
	abstract = {BACKGROUND: Pyogenic lacrimal gland abscesses are uncommon and thus may not be immediately clinically recognized without a high index of suspicion. FINDINGS: We present two patients with preseptal cellulitis and characteristic low-attenuation fluid collections in the lacrimal glands demonstrated on computed tomography (CT). CONCLUSIONS: Lacrimal gland abscesses should be considered when dacryoadenitis is refractory to medical treatment. Indeed, these cases highlight the value of prompt recognition of lacrimal abscess through ophthalmologic referral and the use of diagnostic imaging. Both patients were successfully treated via incision and drainage.},
	doi = {10.1186/s12348-015-0068-6},
	author = {Ginat, Daniel Thomas and Glass, Lora Rabin Dagi and Yanoga, Fatoumata and Lee, Nahyoung Grace and Freitag, Suzanne K}
}
@article {303896,
	title = {Traumatic globe rupture and herniation into the maxillary sinus.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {30},
	number = {6},
	year = {2014},
	month = {2014 Nov-Dec},
	pages = {e168},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000283},
	author = {Ginat, Daniel Thomas and Freitag, Suzanne K}
}
@article {1354337,
	title = {Comparison of the transmembrane mucins MUC1 and MUC16 in epithelial barrier function},
	journal = {PLoS One},
	volume = {9},
	number = {6},
	year = {2014},
	month = {2014},
	pages = {e100393},
	abstract = {Membrane-anchored mucins are present in the apical surface glycocalyx of mucosal epithelial cells, each mucosal epithelium having at least two of the mucins. The mucins have been ascribed barrier functions, but direct comparisons of their functions within the same epithelium have not been done. In an epithelial cell line that expresses the membrane-anchored mucins, MUC1 and MUC16, the mucins were independently and stably knocked down using shRNA. Barrier functions tested included dye penetrance, bacterial adherence and invasion, transepithelial resistance, tight junction formation, and apical surface size. Knockdown of MUC16 decreased all barrier functions tested, causing increased dye penetrance and bacterial invasion, decreased transepithelial resistance, surprisingly, disruption of tight junctions, and greater apical surface cell area. Knockdown of MUC1 did not decrease barrier function, in fact, barrier to dye penetrance and bacterial invasion increased significantly. These data suggest that barrier functions of membrane-anchored mucins vary in the context of other membrane mucins, and MUC16 provides a major barrier when present.},
	keywords = {Bacterial Adhesion, CA-125 Antigen, Cell Membrane, Coloring Agents, Electric Impedance, Epithelial Cells, Gene Knockdown Techniques, Humans, Membrane Proteins, Mucin-1, Mucous Membrane, Tight Junctions},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0100393},
	author = {Gipson, Ilene K and Spurr-Michaud, Sandra and Tisdale, Ann and Menon, Balaraj B}
}
@article {1363113,
	title = {Age-related changes and diseases of the ocular surface and cornea},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {14},
	year = {2013},
	month = {2013 Dec 13},
	pages = {ORSF48-53},
	abstract = {Aging of the ocular surface and corneal tissues, major components of the visual system, causes major eye disease and results in substantial cost in medical and social terms. These diseases include the highly prevalent dry eye disease that affects the ocular surface and its glands, leading to tear film alterations, discomfort, and decreased vision. Studies show that 14.4\% of the population in the United States older than 50 years have dry eye disease and demonstrate that it is particularly prevalent among women. Annual medical costs per patient with dry eye in the United States are estimated at $783 per year, with an overall medical cost adjusted to prevalence of $3.84 billion per year. Societal costs, which include loss of productivity, are estimated per patient at $11,302 per year, with overall costs adjusted to prevalence of $55.4 billion per year. Because there are few effective treatments for the disease, more research on its etiology and mechanisms is warranted and needed. Increased public education about risk factors for the disease is also required. Another major age-related eye disease of the cornea that leads to vision impairment and potentially blindness if left untreated is Fuchs{\textquoteright} endothelial corneal dystrophy. This disease leads to loss of the endothelial cells on the internal side of the cornea that are responsible for keeping the cornea in the proper hydration state to ensure its transparency to light. The mechanism of cell loss is unknown, and the only treatment available to date is surgical transplantation of the cornea or inner part of the cornea. These medically costly procedures require donor corneas, eye banking, and medical follow-up, with accrued costs. Fuchs{\textquoteright} endothelial corneal dystrophy is a major cause of corneal transplantation in the United States; therefore, research support is needed to determine the mechanism of this age-related disease, to develop medical, nonsurgical methods for treatment.},
	keywords = {Aging, Conjunctiva, Conjunctival Diseases, Cornea, Corneal Diseases, Disease Progression, Global Health, Humans, Morbidity, Prognosis},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12840},
	author = {Gipson, Ilene K}
}
@article {913456,
	title = {Goblet cells of the conjunctiva: A review of recent findings.},
	journal = {Prog Retin Eye Res},
	volume = {54},
	year = {2016},
	month = {2016 Sep},
	pages = {49-63},
	abstract = {Goblet cells within the conjunctival epithelium are specialized cells that secrete mucins onto the surface of the eye. Recent research has demonstrated new characteristics of the cells, including factors influencing their differentiation, their gene products and their functions at the ocular surface. The following review summarizes the newly discovered aspects of the role of Spdef, a member of the Ets transcription factor family in conjunctival goblet cell differentiation, the newly discovered goblet cell products including claudin2, the Wnt inhibitor Frzb, and the transmembrane mucin Muc16. The current concepts of conjunctival goblet cell function, including debris removal and immune surveillance are reviewed, as are changes in the goblet cell population in ocular surface diseases. Major remaining questions regarding conjunctival cell biology are discussed.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2016.04.005},
	author = {Gipson, Ilene K}
}
@article {1195276,
	title = {Generation and characterization of a monoclonal antibody to the cytoplasmic tail of MUC16},
	journal = {Glycobiology},
	volume = {27},
	number = {10},
	year = {2017},
	month = {2017 Oct 01},
	pages = {920-926},
	abstract = {MUC16 is a large transmembrane mucin expressed on the apical surfaces of the epithelium covering the ocular surface, respiratory system and female reproductive tract. The transmembrane mucin is overexpressed by ovarian carcinomas, it is one of the most frequently used diagnostic markers for the disease and it is considered a promising target for immunotherapeutic intervention. Immunodetection of the mucin has to date been through antibodies that recognize its exceptionally large ectodomain. Similar to other membrane anchored mucins, MUC16 has a short cytoplasmic tail (CT), but studies of the biological relevance of the C-terminal domain of MUC16 has been limited by lack of availability of monoclonal antibodies that recognize the native CT. Here, we report the development of a novel monoclonal antibody to the CT region of the molecule that recognizes native MUC16 and its enzymatically released CT region. The antibody is useful for immunoprecipitation of the released CT domain as demonstrated with the OVCAR3 ovarian cancer cell line and can be used for detailed cytolocalization in cells as well as in frozen sections of ocular surface and uterine epithelium.},
	issn = {1460-2423},
	doi = {10.1093/glycob/cwx054},
	author = {Gipson, Ilene K and Mandel, Ulla and Menon, Balaraj and Michaud, Sandra and Tisdale, Ann and Campos, Diana and Clausen, Henrik}
}
@article {1658656,
	title = {RNA-based therapies in inherited retinal diseases},
	journal = {Ther Adv Ophthalmol},
	volume = {14},
	year = {2022},
	month = {2022 Jan-Dec},
	pages = {25158414221134602},
	abstract = {Inherited retinal diseases (IRDs) are a genetically and phenotypically heterogeneous group of genetic eye disorders. There are more than 300 disease entities, and together this group of disorders affects millions of people globally and is a frequent cause of blindness or low-vision certification. However, each type is rare or ultra-rare. Characteristically, the impaired vision in IRDs is due to retinal photoreceptor dysfunction and loss resulting from mutation in a gene that codes for a retinal protein. Historically, IRDs have been considered incurable and individuals living with these blinding conditions could be offered only supportive care. However, the treatment landscape for IRDs is beginning to evolve. Progress is being made, driven by improvements in understanding of genotype-phenotype relationships, through advances in molecular genetic testing and retinal imaging. Alongside this expanding knowledge of IRDs, the current era of precision medicine is fueling a growth in targeted therapies. This has resulted in the first treatment for an IRD being approved. Several other therapies are currently in development in the IRD space, including RNA-based therapies, gene-based therapies (such as augmentation therapy and gene editing), cell therapy, visual prosthetics, and optogenetics. RNA-based therapies are a novel approach within precision medicine that have demonstrated success, particularly in rare diseases. Three antisense oligonucleotides (AONs) are currently in development for the treatment of specific IRD subtypes. These RNA-based therapies bring several key advantages in the setting of IRDs, and the potential to bring meaningful vision benefit to individuals living with inherited blinding disorders. This review will examine the increasing breadth and relevance of RNA-based therapies in clinical medicine, explore the key features that make AONs suitable for treating genetic eye diseases, and provide an overview of the three-leading investigational AONs in clinical trials.},
	issn = {2515-8414},
	doi = {10.1177/25158414221134602},
	author = {Girach, Aniz and Audo, Isabelle and Birch, David G and Huckfeldt, Rachel M and Lam, Byron L and Leroy, Bart P and Michaelides, Michel and Russell, Stephen R and Sallum, Juliana M F and Stingl, Katarina and Tsang, Stephen H and Yang, Paul}
}
@article {1498258,
	title = {Update on Pediatric Optic Neuritis},
	journal = {Curr Neurol Neurosci Rep},
	volume = {20},
	number = {3},
	year = {2020},
	month = {2020 Mar 03},
	pages = {4},
	abstract = {PURPOSE OF REVIEW: The purpose of this review is to provide an update on advances in the understanding of pediatric demyelinating optic neuritis. RECENT FINDINGS: In the past decade, the disease phenotypes for demyelinating syndromes in children have been more clearly defined. Pediatric optic neuritis may present as a clinically isolated syndrome or in the setting of underlying neurologic disease. In addition to optic neuritis associated with multiple sclerosis or neuromyelitis optica, recent work has identified antibodies to the myelin oligodendrocyte glycoprotein (MOG IgG) as a unique demyelinating cause with distinct features regarding treatment and prognosis. The disease phenotypes for demyelinating pediatric optic neuritis have expanded. Treatment strategies vary and are not universally effective for each cause of demyelinating disease. Accurately distinguishing among these unique clinical syndromes is therefore critical for initiation of appropriate treatment to prevent disability, to maximize visual outcomes, and to provide insight into long-term prognosis.},
	issn = {1534-6293},
	doi = {10.1007/s11910-020-1024-x},
	author = {Gise, Ryan A and Heidary, Gena}
}
@article {1517191,
	title = {Mycoplasma Pneumoniae-Induced Rash and Mucositis: A Longitudinal Perspective and Proposed Management Criteria},
	journal = {Am J Ophthalmol},
	volume = {219},
	year = {2020},
	month = {2020 11},
	pages = {351-356},
	abstract = {PURPOSE: To evaluate the natural history and ophthalmologic morbidity of Mycoplasma pneumoniae-induced rash and mucositis (MIRM) and propose a treatment algorithm. DESIGN: Retrospective, interventional case series. METHODS: Retrospective chart review of all MIRM patients examined by the department of ophthalmology at a tertiary children{\textquoteright}s hospital. Diagnosis was established clinically concomitant with either positive Mycoplasma pneumoniae IgM or PCR testing from January 1, 2010, until December 31, 2019. The main outcome measures were best-corrected visual acuity, long-term ocular sequelae, and duration and type of ophthalmic intervention. RESULTS: There were 15 patients (10 male and 5 female) aged 10.9 {\textpm} 4.2 years who had primary episodes of MIRM; of those, 4 had multiple episodes. All patients required topical steroid treatment, 3 required amniotic membrane transplantation, and 1 patient underwent placement of a sutureless biologic corneal badage device. There were no patients who suffered visual loss, but 1 was left with mild symblephara near the lateral canthus in each eye and 2 others had scarring of the eyelid margins and blepharitis. CONCLUSIONS: The ocular morbidity is significantly less in MIRM than in other closely related syndromes such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. However, these patients still require close observation and a low threshold for intervention to avoid permanent ophthalmic sequelae and possible blindness.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.06.010},
	author = {Gise, Ryan and Elhusseiny, Abdelrahman M and Scelfo, Christina and Mantagos, Iason S}
}
@article {1664967,
	title = {The visual morbidity of optic nerve head drusen: a longitudinal review},
	journal = {J AAPOS},
	volume = {27},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {30.e1-30.e5},
	abstract = {BACKGROUND: The ophthalmologic complications of optic nerve head drusen (ONHD) in adults have been documented, whereas data on the degree of visual morbidity from OHND in children are limited. METHODS: The medical records of all patients diagnosed with ONHD at a single, tertiary care ophthalmology department from January 1, 2010, until July 1, 2018, were reviewed retrospectively. Patients were identified using ICD-9 and ICD-10 codes. Inclusion criteria were age <=18 years of age and formal documentation of ONHD by ancillary testing. RESULTS: A total of 213 patients (386 eyes with ONHD) met inclusion criteria. Mean age at diagnosis was 10.13 {\textpm} 4.09 years, and mean follow-up was 2.76 {\textpm} 2.91 years. Formal visual fields were available for 208 eyes. Repeatable visual field defects were noted in 24 eyes (11.5\%). The most common defect was a nasal step, which occurred in 11 eyes (45.8\%). Fifteen eyes had visual field defects at presentation, and 9 eyes developed field loss within 1.39 {\textpm} 0.55 years of diagnosis. There was no correlation found between intraocular pressure and degree of visual field loss. Choroidal neovascular membranes were clinically apparent in 5 eyes and treatment was required in 3 eyes. Nonarteritic ischemic optic neuropathy developed in 2 eyes. CONCLUSIONS: Visual morbidity associated with ONHD in children is common and may develop in a short period of time after initial diagnosis. There was no correlation found with intraocular pressure.},
	keywords = {Adolescent, Adult, Child, Humans, Morbidity, Optic Disk, Optic Disk Drusen, Retrospective Studies, Tomography, Optical Coherence, Vision Disorders, Visual Field Tests},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.11.016},
	author = {Gise, Ryan and Heidary, Gena}
}
@article {1445345,
	title = {Diagnosis and Imaging of Optic Nerve Head Drusen},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 03},
	pages = {1-8},
	abstract = {The presence of optic nerve swelling in pediatric patients is a frequent cause for referral to pediatric ophthalmologists and neuro-ophthalmologists because this finding can be the harbinger of serious neurologic disease including brain tumor, demyelinating disease, infiltrative disease of the optic nerve, or idiopathic intracranial hypertension. Optic nerve head drusen (ONHD) are common and can be particularly difficult to distinguish from true optic nerve swelling in pediatric patients because the ONHD are typically buried beneath the substance of the optic nerve. Correct identification of ONHD is relevant because of the visual morbidity associated with this condition and because of the need to distinguish pseudopapilledema secondary to ONHD from true optic nerve swelling. A variety of imaging modalities may be employed to evaluate for the presence of ONHD, including ultrasound, optical coherence tomography (OCT), enhanced depth imaging-OCT, fluorescein angiography, fundus autofluorescence, and optical coherence tomography angiography. To date, there is no consensus as to which of these techniques is most accurate and which should be part of a standardized evaluation for children suspected of ONHD. This review examines the recent literature analyzing these diagnostic tools and summarizes data regarding best practices for identifying ONHD.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620804},
	author = {Gise, Ryan and Gaier, Eric D and Heidary, Gena}
}
@article {1559570,
	title = {Ocular involvement in recurrent infectious mucocutaneous eruption (RIME): a variation on a theme},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Dec 18},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.10.003},
	author = {Gise, Ryan and Elhusseiny, Abdelrahman M and Scelfo, Christina and Mantagos, Iason S}
}
@article {1532332,
	title = {Survey of ophthalmology in the time of COVID-19},
	journal = {Surv Ophthalmol},
	volume = {65},
	number = {5},
	year = {2020},
	month = {2020 Sep - Oct},
	pages = {495},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2020.05.002},
	author = {Gittinger, John W}
}
@article {1589765,
	title = {Charting the Globe: How Technologies Have Affected Our Understanding of Retinal Findings in Abusive Head Trauma/Shaken Baby Syndrome},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {205-209},
	abstract = {Purpose: Ocular findings such as retinal hemorrhages are common in abusive head trauma (AHT). Binocular indirect ophthalmoscopy has been the standard for assessing the eyes of children who are victims of AHT. However, technological advances have changed our understanding of retinal findings in AHT.Methods: Literature review on AHT - retinal findings, imaging technologies, models of representation, and telemedicine applications.Results: Many studies suggest vitreoretinal traction from repetitive acceleration-deceleration shearing forces during shaking plays an important role in the development of retinal findings in AHT. This is further supported by different imaging modalities [optical coherence tomography (OCT); magnetic resonance imaging (MRI); fluorescein angiography (FA)] and models of representation (animal and mechanical models; finite element analysis).Conclusion: Emerging technologies have augmented our diagnostic abilities, enhanced our understanding regarding the pathophysiology of retinal findings, and strengthened the link between vitreoretinal traction and ocular pathology in AHT. Telemedicine is also starting to play an important role in AHT.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1890150},
	author = {Gjerde, Harald and Mantagos, Iason S}
}
@article {541341,
	title = {Management of orbital IgG4-related disease.},
	journal = {Curr Opin Ophthalmol},
	year = {2015},
	month = {2015 Sep 11},
	abstract = {PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is a systemic process that can cause significant orbital disease. It can affect both sexes and all ages, with irreversible consequences if left untreated. Diagnosis is currently based upon a combination of clinical and imaging evidence of tissue swelling or mass, serum evidence of elevated IgG4 levels and histopathologic evidence of inappropriate IgG4 presence. The cause of IgG4-RD is as of yet unclear; this lack of understanding and the dearth of prospective studies have limited our ability to manage patients effectively. In this review, we discuss the most recent published evidence regarding best-practice management of IgG4-related orbital disease. RECENT FINDINGS: Recent literature remains retrospective, and has focused on the use of corticosteroid therapy as a first-line treatment. Rituximab infusions have also received significant attention, among other second-line agents. Radiation therapy has been reported to be effective. Long-term monitoring for relapse, involvement of other organ systems and potential neoplastic transformation is required. SUMMARY: The management of orbital IgG4-RD will gain from more targeted therapy in the future as the underlying cause is better understood. In the meantime, randomized, controlled trials of varying treatment regimens would be of benefit.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000204},
	author = {Glass, Lora R Dagi Glass and Freitag, Suzanne K}
}
@article {1532331,
	title = {Five-Year Outcomes after Initial Aflibercept, Bevacizumab, or Ranibizumab Treatment for Diabetic Macular Edema (Protocol T Extension Study)},
	journal = {Ophthalmology},
	volume = {127},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {1201-1210},
	abstract = {PURPOSE: Assess follow-up treatment and clinical outcomes at 5 years in eyes initially treated with anti-VEGF therapy for center-involved diabetic macular edema (CI-DME) in a 2-year randomized clinical trial. DESIGN: Multicenter cohort study. PARTICIPANTS: Participants with diabetic macular edema (DME) and visual acuity (VA) 20/32 to 20/320 enrolled in DRCR.net Protocol T with visits 5 years after randomization (3 years after Protocol T completion). METHODS: Participants were assigned randomly to aflibercept, bevacizumab, or ranibizumab with protocol-defined follow-up and re-treatment for 2 years. Thereafter, participants were managed at clinician discretion and recalled for a 5-year visit. MAIN OUTCOME MEASURES: Anti-vascular endothelial growth factor (VEGF) treatment, VA letter score, and central subfield thickness (CST). RESULTS: Sixty-eight percent (317/463) of eligible participants completed the 5-year visit. Between years 2 and 5, 68\% (217/317) of study eyes received at least 1 anti-VEGF treatment (median, 4; interquartile range [IQR], 0-12). At 5 years, mean VA improved from baseline by 7.4 letters (95\% confidence interval [CI], 5.9-9.0) but decreased by 4.7 letters (95\% CI, 3.3-6.0) between 2 and 5 years. When baseline VA was 20/50 to 20/320, mean 5-year VA was 11.9 letters (95\% CI, 9.3-14.5) better than baseline but 4.8 letters (95\% CI, 2.5-7.0) worse than 2 years. When baseline VA was 20/32 to 20/40, mean 5-year VA was 3.2 letters (95\% CI, 1.4-5.0) better than baseline but 4.6 letters (95\% CI, 3.1-6.1) worse than 2 years. Mean CST decreased from baseline to 5 years by 154 μm (95\% CI, 142-166) and was stable between 2 and 5 years (-1 μm; 95\% CI,\&nbsp;-12 to 9). CONCLUSIONS: Among the two-thirds of eligible Protocol T participants who completed a 5-year visit, mean VA improved from baseline to 5 years without protocol-defined treatment after follow-up ended at 2 years. Although mean retinal thickness was similar at 2 and 5 years, mean VA worsened during this period. Additional investigation into strategies to improve long-term outcomes in eyes with DME seems warranted to determine if VA can be better maintained with different management approaches.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.03.021},
	author = {Glassman, Adam R and Wells, John A and Josic, Kristin and Maguire, Maureen G and Antoszyk, Andrew N and Baker, Carl and Beaulieu, Wesley T and Elman, Michael J and Jampol, Lee M and Sun, Jennifer K}
}
@article {1483595,
	title = {Effect of telephone calls from a centralized coordinating center on participant retention in a randomized clinical trial},
	journal = {Clin Trials},
	year = {2020},
	month = {2020 Jan 27},
	pages = {1740774519894229},
	abstract = {BACKGROUND/AIMS: In clinical trials, participant retention is critical to reduce bias and maintain statistical power for hypothesis testing. Within a multi-center clinical trial of diabetic retinopathy, we investigated whether regular phone calls to participants from the coordinating center improved long-term participant retention. METHODS: Among 305 adults in the Diabetic Retinopathy Clinical Research Retina Network Protocol S randomized trial, 152 participants were randomly assigned to receive phone calls at baseline, 6 months, and annually through 3 years (annual contact group) while 153 participants were assigned to receive a phone call at baseline only (baseline contact group). All participants could be contacted if visits were missed. The main outcomes were visit completion, excluding deaths, at 2 years (the primary outcome time point) and at 5 years (the final time point). RESULTS: At baseline, 77\% (117 of 152) of participants in the annual contact group and 76\% (116 of 153) in the baseline contact group were successfully contacted. Among participants in the annual contact group active at each annual visit (i.e. not dropped from the study or deceased), 85\% (125 of 147), 79\% (108 of 136), and 88\% (110 of 125) were contacted successfully by telephone around the time of the 1-, 2-, and 3-year visits, respectively. In the annual and baseline contact groups, completion rates for the 2-year primary outcome visit were 88\% (129 of 147) versus 87\% (125 of 144), respectively, with a risk ratio of 1.01 (95\% confidence interval: 0.93-1.10,  = .81). At 5 years, the final study visit, participant completion rates were 67\% (96 of 144) versus 66\% (88 of 133) with a risk ratio of 1.01 (95\% confidence interval = 0.85-1.19,  = .93). At 2 years, the completion rate of participants successfully contacted at baseline was 89\% (202 of 226) versus 80\% (52 of 65) among those not contacted successfully (risk ratio = 1.12, 95\% confidence interval = 0.98-1.27,  = .09); at 5 years, the completion percentages by baseline contact success were 69\% (148 of 213) versus 56\% (36 of 64; risk ratio = 1.24, 95\% confidence interval = 0.98-1.56,  = .08). CONCLUSION: Regular phone calls from the coordinating center to participants during follow-up in this randomized clinical trial did not improve long-term participant retention.},
	issn = {1740-7753},
	doi = {10.1177/1740774519894229},
	author = {Glassman, Adam R and Beaulieu, Wesley T and Stockdale, Cynthia R and Beck, Roy W and Bressler, Neil M and Labriola, Leanne T and Melia, Michele and Oliver, Kristina and Sun, Jennifer K}
}
@article {1593851,
	title = {Visual Acuity, Vitreous Hemorrhage, and Other Ocular Outcomes After Vitrectomy vs Aflibercept for Vitreous Hemorrhage Due to Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {7},
	year = {2021},
	month = {2021 Jul 01},
	pages = {725-733},
	abstract = {Importance: Although there were no differences in mean visual acuity (VA) over 24 weeks after vitrectomy with panretinal photocoagulation (PRP) vs aflibercept in a randomized clinical trial among eyes with vitreous hemorrhage due to proliferative diabetic retinopathy (PDR), post hoc analyses may influence treatment choices. Objective: To compare exploratory outcomes between treatment groups that may affect treatment choices for patients with vitreous hemorrhage due to PDR. Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial conducted at 39 DRCR Retina Network sites included adults with vision loss due to PDR-related vitreous hemorrhage for whom vitrectomy was considered. Data were collected from November 2016 to January 2020. Interventions: Random assignment to 4 monthly injections of aflibercept vs vitrectomy with PRP. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol-specific criteria. Main Outcomes and Measures: Visual acuity area under the curve (adjusted for baseline VA) and clearance of vitreous hemorrhage. Results: A total of 205 eyes were included in the analysis (115 male [56\%] and 90 [44\%] female participants; mean [SD] age, 57 [11] years). Among 89 eyes with a baseline VA of 20/32 to 20/160 (47 receiving aflibercept, including 4 [9\%] that had undergone vitrectomy; 42 undergoing vitrectomy, including 3 [7\%] that had received aflibercept), the adjusted mean difference in VA letter score over 24 weeks between the aflibercept and vitrectomy groups was -4.3 (95\% CI, -10.6 to 1.9) compared with -16.7 (95\% CI, -24.4 to -9.1) among 59 eyes with baseline VA worse than 20/800 (P = .02 for interaction; 26 in the aflibercept group, including 6 [23\%] that had undergone vitrectomy; 33 in the vitrectomy group, including 8 [24\%] that had received aflibercept). In the full cohort, the median time to clearance of the initial vitreous hemorrhage was 36 (interquartile range [IQR], 24-52) weeks in the aflibercept group vs 4 (IQR, 4-4) weeks in the vitrectomy group (difference, 32 [95\% CI, 20-32] weeks; P \&lt; .001). Conclusions and Relevance: Both initial aflibercept and vitrectomy with PRP are viable treatment approaches for PDR-related vitreous hemorrhage. Although this study did not find a significant difference between groups in the primary outcome of mean VA over 24 weeks of follow-up, eyes receiving initial vitrectomy with PRP had faster recovery of vision over 24 weeks when baseline VA was worse than 20/800 and faster vitreous hemorrhage clearance. Approximately one-third of the eyes in each group received the alternative treatment (aflibercept or vitrectomy with PRP). These factors may influence treatment decisions for patients initiating therapy for PDR-related vitreous hemorrhage. Trial Registration: ClinicalTrials.gov Identifier: NCT02858076.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.1110},
	author = {Glassman, Adam R and Beaulieu, Wesley T and Maguire, Maureen G and Antoszyk, Andrew N and Chow, Clement C and Elman, Michael J and Jampol, Lee M and Salehi-Had, Hani and Sun, Jennifer K and DRCR Retina Network}
}
@article {1490439,
	title = {Assessment of the DRCR Retina Network Approach to Management With Initial Observation for Eyes With Center-Involved Diabetic Macular Edema and Good Visual Acuity: A Secondary Analysis of a Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Feb 20},
	abstract = {Importance: Among eyes with center-involved diabetic macular edema (CI-DME) and good visual acuity (VA), randomized clinical trial results showed no difference in VA loss between initial observation plus aflibercept only if VA decreased, initial focal/grid laser plus aflibercept only if VA decreased, or prompt aflibercept. Understanding the initial observation approach is relevant to patient management. Objective: To assess the DRCR Retina Network protocol-defined approach and outcomes of initial observation with aflibercept only if VA worsened. Design, Setting, and Participants: This was a post hoc secondary analyses of a randomized clinical trial of the DRCR Retina Network Protocol V that included 91 US and Canadian sites from November 2013 to September 2018. Participants were adults (n = 236) with type 1 or 2 diabetes, 1 study eye with CI-DME, and VA letter score at least 79 (Snellen equivalent, 20/25 or better) assigned to initial observation. Data were analyzed from March 2019 to November 2019. Interventions: Initial observation and follow-up with aflibercept only for VA loss of at least 10 letters from baseline at 1 visit or 5 to 9 letters at 2 consecutive visits. Follow-up occurred at 8 weeks and then every 16 weeks unless VA or optical coherence tomography central subfield thickness worsened. Main Outcomes and Measures: Whether individuals received aflibercept. Results: Among 236 eyes in 236 individuals (149 [63\%] male; median age, 60 years [interquartile range, 53-67 years]) randomly assigned to initial observation, 80 (34\%) were treated with aflibercept during 2 years of follow-up. At 2 years, the median VA letter score was 86.0 (interquartile range, 89.0-81.0; median Snellen equivalent, 20/20 [20/16-20/25]). Receipt of aflibercept was more likely in eyes with baseline central subfield thickness at least 300 μm (Zeiss-Stratus equivalent) vs less than 300 μm (45\% vs 26\%; hazard ratio [HR], 1.98 [95\% CI, 1.26-3.13], continuous P = .005), moderately severe nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study retinopathy severity level 47) and above vs moderate nonproliferative diabetic retinopathy (retinopathy severity level 43) and below (51\% vs 27\%; HR, 2.22 [95\% CI, 1.42-3.47], ordinal P \&lt; .001), and among participants whose nonstudy eye received DME treatment within 4 months of randomization vs not (52\% vs 25\%; HR, 2.55 [95\% CI, 1.64-3.99], P \&lt; .001). Conclusions and Relevance: Most eyes managed with initial observation plus aflibercept only if VA worsened maintained good vision at 2 years and did not require aflibercept for VA loss. However, the eyes in the trial were approximately twice as likely to receive aflibercept for VA loss if they had greater baseline central subfield thickness, worse diabetic retinopathy severity level, or a nonstudy eye receiving treatment for DME. Trial Registration: ClinicalTrials.gov Identifier: NCT01909791.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.6035},
	author = {Glassman, Adam R and Baker, Carl W and Beaulieu, Wesley T and Bressler, Neil M and Punjabi, Omar S and Stockdale, Cynthia R and Wykoff, Charles C and Jampol, Lee M and Sun, Jennifer K and DRCR Retina Network}
}
@article {1490445,
	title = {Global Retinoblastoma Presentation and Analysis by National Income Level},
	journal = {JAMA Oncol},
	year = {2020},
	month = {2020 Feb 27},
	abstract = {Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child{\textquoteright}s life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4\%) were female. Most patients (n = 3685 [84.7\%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8\%]), followed by strabismus (n = 429 [10.2\%]) and proptosis (n = 309 [7.4\%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5\%) patients having intraocular retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95\% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95\% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.},
	issn = {2374-2445},
	doi = {10.1001/jamaoncol.2019.6716},
	author = {Global Retinoblastoma Study Group and Fabian, Ido Didi and Abdallah, Elhassan and Abdullahi, Shehu U and Abdulqader, Rula A and Adamou Boubacar, Sahadatou and Ademola-Popoola, Dupe S and Adio, Adedayo and Afshar, Armin R and Aggarwal, Priyanka and Aghaji, Ada E and Ahmad, Alia and Akib, Marliyanti N R and Al Harby, Lamis and Al Ani, Mouroge H and Alakbarova, Aygun and Portabella, Silvia Alarc{\'o}n and Al-Badri, Safaa A F and Alcasabas, Ana Patricia A and Al-Dahmash, Saad A and Alejos, Amanda and Alemany-Rubio, Ernesto and Alfa Bio, Amadou I and Alfonso Carreras, Yvania and Al-Haddad, Christiane and Al-Hussaini, Hamoud H Y and Ali, Amany M and Alia, Donjeta B and Al-Jadiry, Mazin F and Al-Jumaly, Usama and Alkatan, Hind M and All-Eriksson, Charlotta and Al-Mafrachi, Ali A R M and Almeida, Argentino A and Alsawidi, Khalifa M and Al-Shaheen, Athar A S M and Al-Shammary, Entissar H and Amiruddin, Primawita O and Antonino, Romanzo and Astbury, Nicholas J and Atalay, Hatice T and Atchaneeyasakul, La-Ongsri and Atsiaya, Rose and Attaseth, Taweevat and Aung, Than H and Ayala, Silvia and Baizakova, Baglan and Balaguer, Julia and Balayeva, Ruhengiz and Balwierz, Walentyna and Barranco, Honorio and Bascaran, Covadonga and Beck Popovic, Maja and Benavides, Raquel and Benmiloud, Sarra and Bennani Guebessi, Nissrine and Berete, Rokia C and Berry, Jesse L and Bhaduri, Anirban and Bhat, Sunil and Biddulph, Shelley J and Biewald, Eva M and Bobrova, Nadia and Boehme, Marianna and Boldt, H C and Bonanomi, Maria Teresa B C and Bornfeld, Norbert and Bouda, Gabrielle C and Bouguila, H{\'e}di and Boumedane, Amaria and Brennan, Rachel C and Brichard, B{\'e}n{\'e}dicte G and Buaboonnam, Jassada and Calder{\'o}n-Sotelo, Patricia and Calle Jara, Doris A and Camuglia, Jayne E and Cano, Miriam R and Capra, Michael and Cassoux, Nathalie and Castela, Guilherme and Castillo, Luis and Catal{\`a}-Mora, Jaume and Chantada, Guillermo L and Chaudhry, Shabana and Chaugule, Sonal S and Chauhan, Argudit and Chawla, Bhavna and Chernodrinska, Violeta S and Chiwanga, Faraja S and Chuluunbat, Tsengelmaa and Cieslik, Krzysztof and Cockcroft, Ruellyn L and Comsa, Codruta and Correa, Zelia M and Correa Llano, Maria G and Corson, Timothy W and Cowan-Lyn, Kristin E and Cs{\'o}ka, Monika and Cui, Xuehao and Da Gama, Isac V and Dangboon, Wantanee and Das, Anirban and Das, Sima and Davanzo, Jacquelyn M and Davidson, Alan and De Potter, Patrick and Delgado, Karina Q and Demirci, Hakan and Desjardins, Laurence and Diaz Coronado, Rosdali Y and Dimaras, Helen and Dodgshun, Andrew J and Donaldson, Craig and Donato Macedo, Carla R and Dragomir, Monica D and Du, Yi and Du Bruyn, Magritha and Edison, Kemala S and Eka Sutyawan, I Wayan and El Kettani, Asmaa and Elbahi, Amal M and Elder, James E and Elgalaly, Dina and Elhaddad, Alaa M and Elhassan, Moawia M Ali and Elzembely, Mahmoud M and Essuman, Vera A and Evina, Ted Grimbert A and Fadoo, Zehra and Fandi{\~n}o, Adriana C and Faranoush, Mohammad and Fasina, Oluyemi and Fern{\'a}ndez, Delia D P G and Fern{\'a}ndez-Teijeiro, Ana and Foster, Allen and Frenkel, Shahar and Fu, Ligia D and Fuentes-Alabi, Soad L and Gallie, Brenda L and Gandiwa, Moira and Garcia, Juan L and Garc{\'\i}a Aldana, David and Gassant, Pascale Y and Geel, Jennifer A and Ghassemi, Fariba and Gir{\'o}n, Ana V and Gizachew, Zelalem and Goenz, Marco A and Gold, Aaron S and Goldberg-Lavid, Maya and Gole, Glen A and Gomel, Nir and Gonzalez, Efren and Gonzalez Perez, Graciela and Gonz{\'a}lez-Rodr{\'\i}guez, Liudmira and Garcia Pacheco, Henry N and Graells, Jaime and Green, Liz and Gregersen, Pernille A and Grigorovski, Nathalia D A K and Guedenon, Koffi M and Gunasekera, D Sanjeeva and G{\"u}nd{\"u}z, Ahmet K and Gupta, Himika and Gupta, Sanjiv and Hadjistilianou, Theodora and Hamel, Patrick and Hamid, Syed A and Hamzah, Norhafizah and Hansen, Eric D and Harbour, J William and Hartnett, M Elizabeth and Hasanreisoglu, Murat and Hassan, Sadiq and Hassan, Shadab and Hederova, Stanislava and Hernandez, Jose and Hernandez, Lorelay Marie Carcamo and Hessissen, Laila and Hordofa, Diriba F and Huang, Laura C and Hubbard, G B and Hummlen, Marlies and Husakova, Kristina and Hussein Al-Janabi, Allawi N and Ida, Russo and Ilic, Vesna R and Jairaj, Vivekaraj and Jeeva, Irfan and Jenkinson, Helen and Ji, Xunda and Jo, Dong Hyun and Johnson, Kenneth P and Johnson, William J and Jones, Michael M and Kabesha, Theophile B Amani and Kabore, Rolande L and Kaliki, Swathi and Kalinaki, Abubakar and Kantar, Mehmet and Kao, Ling-Yuh and Kardava, Tamar and Kebudi, Rejin and Kepak, Tomas and Keren-Froim, Naama and Khan, Zohora J and Khaqan, Hussain A and Khauv, Phara and Kheir, Wajiha J and Khetan, Vikas and Khodabande, Alireza and Khotenashvili, Zaza and Kim, Jonathan W and Kim, Jeong Hun and Kiratli, Hayyam and Kivel{\"a}, Tero T and Klett, Artur and Komba Palet, Jess Elio Kosh and Krivaitiene, Dalia and Kruger, Mariana and Kulvichit, Kittisak and Kuntorini, Mayasari W and Kyara, Alice and Lachmann, Eva S and Lam, Carol P S and Lam, Geoffrey C and Larson, Scott A and Latinovic, Slobodanka and Laurenti, Kelly D and Le, Bao Han A and Lecuona, Karin and Leverant, Amy A and Li, Cairui and Limbu, Ben and Long, Quah Boon and L{\'o}pez, Juan P and Lukamba, Robert M and Lumbroso, Livia and Luna-Fineman, Sandra and Lutfi, Delfitri and Lysytsia, Lesia and Magrath, George N and Mahajan, Amita and Majeed, Abdul Rahim and Maka, Erika and Makan, Mayuri and Makimbetov, Emil K and Manda, Chatonda and Mart{\'\i}n Begue, Nieves and Mason, Lauren and Mason, John O and Matende, Ibrahim O and Materin, Miguel and Mattosinho, Clarissa C D S and Matua, Marchelo and Mayet, Ismail and Mbumba, Freddy B and McKenzie, John D and Medina-Sanson, Aurora and Mehrvar, Azim and Mengesha, Aemero A and Menon, Vikas and Mercado, Gary John V D and Mets, Marilyn B and Midena, Edoardo and Mishra, Divyansh K C and Mndeme, Furahini G and Mohamedani, Ahmed A and Mohammad, Mona T and Moll, Annette C and Montero, Margarita M and Morales, Rosa A and Moreira, Claude and Mruthyunjaya, Prithvi and Msina, Mchikirwa S and Msukwa, Gerald and Mudaliar, Sangeeta S and Muma, Kangwa I and Munier, Francis L and Murgoi, Gabriela and Murray, Timothy G and Musa, Kareem O and Mushtaq, Asma and Mustak, Hamzah and Muyen, Okwen M and Naidu, Gita and Nair, Akshay Gopinathan and Naumenko, Larisa and Ndoye Roth, Paule A{\"\i}da and Nency, Yetty M and Neroev, Vladimir and Ngo, Hang and Nieves, Rosa M and Nikitovic, Marina and Nkanga, Elizabeth D and Nkumbe, Henry and Nuruddin, Murtuza and Nyaywa, Mutale and Obono-Obiang, Ghislaine and Oguego, Ngozi C and Olechowski, Andrzej and Oliver, Scott C N and Osei-Bonsu, Peter and Ossandon, Diego and Paez-Escamilla, Manuel A and Pagarra, Halimah and Painter, Sally L and Paintsil, Vivian and Paiva, Luisa and Pal, Bikramjit P and Palanivelu, Mahesh Shanmugam and Papyan, Ruzanna and Parrozzani, Raffaele and Parulekar, Manoj and Pascual Morales, Claudia R and Paton, Katherine E and Pawinska-Wasikowska, Katarzyna and Pe{\textquoteright}er, Jacob and Pe{\~n}a, Armando and Peric, Sanja and Pham, Chau T M and Philbert, Remezo and Plager, David A and Pochop, Pavel and Polania, Rodrigo A and Polyakov, Vladimir G and Pompe, Manca T and Pons, Jonathan J and Prat, Daphna and Prom, Vireak and Purwanto, Ignatius and Qadir, Ali O and Qayyum, Seema and Qian, Jiang and Rahman, Ardizal and Rahman, Salman and Rahmat, Jamalia and Rajkarnikar, Purnima and Ramanjulu, Rajesh and Ramasubramanian, Aparna and Ramirez-Ortiz, Marco A and Raobela, L{\'e}a and Rashid, Riffat and Reddy, M Ashwin and Reich, Ehud and Renner, Lorna A and Reynders, David and Ribadu, Dahiru and Riheia, Mussagy M and Ritter-Sovinz, Petra and Rojanaporn, Duangnate and Romero, Livia and Roy, Soma R and Saab, Raya H and Saakyan, Svetlana and Sabhan, Ahmed H and Sagoo, Mandeep S and Said, Azza M A and Saiju, Rohit and Salas, Beatriz and San Rom{\'a}n Pacheco, Sonsoles and S{\'a}nchez, Gissela L and Sayalith, Phayvanh and Scanlan, Trish A and Schefler, Amy C and Schoeman, Judy and Sedaghat, Ahad and Seregard, Stefan and Seth, Rachna and Shah, Ankoor S and Shakoor, Shawkat A and Sharma, Manoj K and Sherief, Sadik T and Shetye, Nandan G and Shields, Carol L and Siddiqui, Sorath Noorani and Sidi Cheikh, Sidi and Silva, S{\'o}nia and Singh, Arun D and Singh, Niharika and Singh, Usha and Singha, Penny and Sitorus, Rita S and Skalet, Alison H and Soebagjo, Hendrian D and Sorochynska, Tetyana and Ssali, Grace and Stacey, Andrew W and Staffieri, Sandra E and Stahl, Erin D and Stathopoulos, Christina and Stirn Kranjc, Branka and Stones, David K and Strahlendorf, Caron and Suarez, Maria Estela Coleoni and Sultana, Sadia and Sun, Xiantao and Sundy, Meryl and Superstein, Rosanne and Supriyadi, Eddy and Surukrattanaskul, Supawan and Suzuki, Shigenobu and Svojgr, Karel and Sylla, Fatoumata and Tamamyan, Gevorg and Tan, Deborah and Tandili, Alketa and Tarrillo Leiva, Fanny F and Tashvighi, Maryam and Tateshi, Bekim and Tehuteru, Edi S and Teixeira, Luiz F and Teh, Kok Hoi and Theophile, Tuyisabe and Toledano, Helen and Trang, Doan L and Traor{\'e}, Fousseyni and Trichaiyaporn, Sumalin and Tuncer, Samuray and Tyau-Tyau, Harba and Umar, Ali B and Unal, Emel and Uner, Ogul E and Urbak, Steen F and Ushakova, Tatiana L and Usmanov, Rustam H and Valeina, Sandra and van Hoefen Wijsard, Milo and Varadisai, Adisai and Vasquez, Liliana and Vaughan, Leon O and Veleva-Krasteva, Nevyana V and Verma, Nishant and Victor, Andi A and Viksnins, Maris and Villac{\'\i}s Chafla, Edwin G and Vishnevskia-Dai, Vicktoria and Vora, Tushar and Wachtel, Antonio E and Wackernagel, Werner and Waddell, Keith and Wade, Patricia D and Wali, Amina H and Wang, Yi-Zhuo and Weiss, Avery and Wilson, Matthew W and Wime, Amelia D C and Wiwatwongwana, Atchareeya and Wiwatwongwana, Damrong and Wolley Dod, Charlotte and Wongwai, Phanthipha and Xiang, Daoman and Xiao, Yishuang and Yam, Jason C and Yang, Huasheng and Yanga, Jenny M and Yaqub, Muhammad A and Yarovaya, Vera A and Yarovoy, Andrey A and Ye, Huijing and Yousef, Yacoub A and Yuliawati, Putu and Zapata L{\'o}pez, Arturo M and Zein, Ekhtelbenina and Zhang, Chengyue and Zhang, Yi and Zhao, Junyang and Zheng, Xiaoyu and Zhilyaeva, Katsiaryna and Zia, Nida and Ziko, Othman A O and Zondervan, Marcia and Bowman, Richard}
}
@article {1782246,
	title = {Retinoblastoma Outcomes in the Americas: a prospective analysis of 491 children with retinoblastoma from 23 American countries},
	journal = {Am J Ophthalmol},
	year = {2023},
	month = {2023 Nov 08},
	abstract = {PURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. DESIGN: Subanalysis of prospective cohort study data. METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income=LIC, lower-middle=LMIC, upper-middle=UMIC, high=HIC) of 491 treatment-na{\"\i}ve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of patients, 8 (1.6\%), 58 (11.8\%), 235 (47.9\%) and 190 (38.7\%) were from LIC, LMIC, UMIC and HIC, respectively. Three-year survival rates in LICs were 60.0\% (95\% CI, 12.6-88.2) compared to 99.2\% (94.6-99.9) in HICs. Death was less likely in patients older than four years (vs. four or younger, HR=0.45 [95\% CI, 0.27 - 0.78], P=0.048). Patients with more advanced tumors (e.g., cT3 vs. cT1, HR= 4.65 {\texttimes} 109 [95\% CI, 1.25 {\texttimes} 109 - 1.72 {\texttimes} 1010], P\&lt;0.001) and females (vs. males, HR=1.98 [1.27-3.10], P=0.04) were more likely to die. Three-year globe salvage rates were 13.3\% (95\% CI, 5.1-25.6) in LMICs and 46.2\% (38.8-53.3) in HICs. At three years, 70.1\% of cT1 eyes (95\% CI, 54.5-81.2) versus 8.9\% of cT3 eyes (5.5-13.3) were salvaged. Advanced tumor stage was associated with higher enucleation risk (e.g., cT3 vs. cT1, SHR=4.98 [95\% CI, 2.36-10.5), P\&lt;0.001). CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.11.004},
	author = {Global Retinoblastoma Study Group and Berry, Jesse L and Pike, Sarah and Rajagopalan, Archeta and Reid, Mark W and Fabian, Ido Didi and Afshar, Armin R and Alejos, Amanda and Alemany-Rubio, Ernesto and Alfonso Carreras, Yvania and Arazi, Mattan and Astbury, Nicholas J and Bascaran, Covadonga and Binkley, Elaine and Blum, Sharon and Boldt, H Culver and Bonanomi, Maria Teresa B C and Bowman, Richard and Brennan, Rachel C and Burton, Matthew J and Calder{\'o}n-Sotelo, Patricia and Jara, Doris A Calle and Cano, Miriam R and Castillo, Luis and Cavieres, Isabel and Cerna, Doris Quiroz and Chandramohan, Arthika and Chantada, Guillermo L and Corson, Timothy W and Cowan-Lyn, Kristin E and Davanzo, Jacquelyn M and Demirci, Hakan and Coronado, Rosdali Y Diaz and Dimaras, Helen and Macedo, Carla R Donato and Ericksen, Connor and Fandi{\~n}o, Adriana C and Fern{\'a}ndez, Delia D P G and Foster, Allen and Fu, Ligia D and Fuentes-Alabi, Soad L and Garcia, Juan L and Pacheco, Henry N Garcia and Gir{\'o}n, Ana V and Goenz, Marco A and Gold, Aaron S and Gomel, Nir and Gonzalez, Efren and Gonzalez Perez, Graciela and Gonz{\'a}lez-Rodr{\'\i}guez, Liudmira and Graells, Jaime and Grigorovski, Nathalia D A K and Hamel, Patrick and Hansen, Eric D and Harbour, J William and Elizabeth Hartnett, M and Hassan, Muhammad and Hubbard, G Baker and Kapelushnik, Noa and Kim, Jonathan W and Larson, Scott A and Laurenti, Kelly D and Leverant, Amy A and Li, Cairui and L{\'o}pez, Juan P and Luna-Fineman, Sandra and Magrath, George N and Mallipatna, Ashwin and Mattosinho, Clarissa C D S and Mets, Marilyn B and Miller, Audra and Mruthyunjaya, Prithvi and Murray, Timothy G and Oliver, Scott C N and Oporto, Joaquin and Ortega-Hern{\'a}ndez, Miriam and Ossandon, Diego and Morales, Claudia R Pascual and Paton, Katherine E and Plager, David A and Polania, Rodrigo A and Ponce, Jimena and Quintero D, Karina and Ramasubramanian, Aparna and Ramirez-Ortiz, Marco A and Randhawa, Jasmeen K and Romero, Livia and Salas, Beatriz and S{\'a}nchez, Gissela L and Orozco, Alma Janeth Sanchez and Sgroi, Mariana and Shah, Ankoor S and Shields, Carol L and Singh, Arun D and Skalet, Alison H and Stacey, Andrew W and Stahl, Erin D and Strahlendorf, Caron and Suarez, Maria Estela Coleoni and Superstein, Rosanne and Leiva, Fanny F Tarrillo and Teixeira, Luiz F and Uner, Ogul E and Anchaya, Jacqueline Karina Vasquez and Vaughan, Leon O and Villegas, Victor M and Wilson, Matthew W and Yaghy, Antonio and Yee, Roberto I and L{\'o}pez, Arturo M and Zondervan, Marcia}
}
@article {1645464,
	title = {Phosphatic metabolism in dark- and light-adapted rat retinas},
	journal = {Exp Eye Res},
	volume = {221},
	year = {2022},
	month = {2022 Jun 06},
	pages = {109141},
	abstract = {This study defines retinal phosphatic metabolites and their adjustment to illumination in rat retinas under conditions that preserve retinal function. Metabolic data are measured using high-performance liquid chromatography (HPLC) and 31P nuclear magnetic resonance (31P NMR) spectroscopy after 10\&nbsp;min of light exposure in vivo compared with retinas from dark-adapted rats. Multiple high-energy and low-energy phosphatic metabolites of intermediary metabolism were quantified. The concentration of the high-energy phosphate adenosine triphosphate (ATP) remained unchanged from dark- to light-adaptation. Under the same conditions the concentrations of the high-energy phosphates guanosine triphosphate (GTP) and creatine phosphate increased, whereas the inorganic phosphate decreased. Comparing dark-adapted controls with retinas light-adapted either in vitro or in vivo, the evidence is consistent with a light-dependent increase in GTP and a decrease in cyclic guanosine monophosphate. Although cyclic adenosine monophosphate (cAMP) levels were lower in retinas light-adapted in vivo than in the dark-adapted controls, this did not seem to be an effect of light, as cAMP levels decreased similarly after 10\&nbsp;min incubation in dark or light in parallel with recovery of ATP/adenosine diphosphate ratios. This study: (1) reports on retinal metabolic changes with adjustment in illumination, (2) provides baseline measurements of retinal phosphatic metabolites in whole retinas, and (3) reports on the validity of chromatographic and spectroscopic methods used for studying retinal metabolism establishing a high correlation among measurements made using HPLC and 31P NMR.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2022.109141},
	author = {Glonek, Thomas and Snogren, Tamara and Schmidt, Susan Y and Hearn, Stacey L and Isreb, Majd A and Greiner, Jack V}
}
@article {1661588,
	title = {Diversity in Academic Ophthalmology: Disparities and Opportunities from Medical School to Practice},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {4},
	year = {2023},
	month = {2023 May},
	pages = {338-343},
	abstract = {INTRODUCTION: Compared to the United States population as a whole, physicians are more likely to identify as men, identify as Asian or non-hispanic White, and be raised in wealthier households. Racial, ethnic, gender, and socioeconomic representation in ophthalmology is often blamed on the pipeline of matriculants. METHODS: This review collects recent data from the US census, AAMC, and primary literature on gender, racial, ethnic, and socioeconomic diversity from medical school to ophthalmology practice. RESULTS: Data from the medical and ophthalmology literature shows that medical students are less diverse than medical school applicants, ophthalmology residencies are less diverse than graduating medical students, and ophthalmology departments are less diverse than those of most other specialties. DISCUSSION: At each level, there are limitations in representation beyond the pipeline of medical school applicants or medical students applying to ophthalmology. There are many practical steps the field can take at each level of training to move the specialty toward more equitable representation.},
	keywords = {Humans, Male, Minority Groups, Ophthalmology, Racial Groups, Schools, Medical, Students, Medical, United States},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2157217},
	author = {Gluckstein, Jeffrey}
}
@article {1789221,
	title = {SARS-CoV-2 Parainfectious Optic Neuropathy: 3 Case Reports and a Review of the Literature},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {4},
	year = {2023},
	month = {2023 Dec 01},
	pages = {491-498},
	abstract = {BACKGROUND: Parainfectious optic neuritis is an inflammatory reaction that occurs shortly after an infection without direct invasion by a pathogen. The clinical profile depends on the infectious organism. Cases of SARS-CoV-2 parainfectious optic neuritis have been reported in the literature, but there are no reviews that have applied strict inclusion criteria to more definitively establish the clinical profile associated with SARS-CoV-2.

METHODS: We present 3 new cases of SARS-CoV-2 parainfectious optic neuritis. We also review the literature for definite cases by selecting only those with unambiguous clinical features and MRI findings of optic neuritis, positive SARS-CoV-2 polymerase chain reaction or serology, and the absence of myelin oligodendrocyte-glycoprotein or aquaporin-4 antibodies or other diseases associated with optic neuritis.

RESULTS: We report 2 cases of monophasic, unilateral SARS-CoV-2 parainfectious optic neuritis with optic disc edema and nadir visual acuities of finger counting. We report 1 case of mild SARS-CoV-2 parainfectious optic neuritis that featured cotton wool spots, peripapillary wrinkles and hemorrhages, and recurrence after an initial steroid taper. We identified 6 cases of unambiguous SARS-CoV-2 parainfectious optic neuritis from the literature. Combining our case series with the case reports in the literature, the average age was 42.8 years, 3/9 had bilateral disease, 6/8 had optic disc edema, 8/9 had nadir visual acuity of finger counting or worse, and all recovered visual acuity to 20/40 or better after therapy with steroids.

CONCLUSIONS: SARS-CoV-2 parainfectious optic neuritis has a clinical profile that is atypical for idiopathic optic neuritis but fairly typical of parainfectious forms of optic neuritis with a severely reduced nadir visual acuity, high likelihood of bilaterality, high incidence of optic disc edema, and prompt and significant response to corticosteroids. Further study with long-term follow-up and epidemiologic investigation will be needed to further characterize this clinical entity.},
	keywords = {COVID-19, Humans, Optic Nerve Diseases, Optic Neuritis, Papilledema, Retrospective Studies, SARS-CoV-2, Vision Disorders},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001822},
	author = {Gluckstein, Jeffrey A and Chwalisz, Bart K and Gilbert, Aubrey L and Bouffard, Marc A}
}
@article {1677796,
	title = {Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis},
	journal = {Development},
	volume = {150},
	number = {5},
	year = {2023},
	month = {2023 Mar 01},
	abstract = {Microglia, a resident immune cell of the central nervous system (CNS), play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. Previous reports indicate a role for microglia in regulating astrocyte density. This current work resolves the mechanism through which microglia facilitate astrocyte spatial patterning and superficial vascular bed formation in the neuroretina during development. Ablation of microglia increased astrocyte density and altered spatial patterning. Mechanistically, we show that microglia regulate the formation of the spatially organized astrocyte template required for subsequent vascular growth, through the complement C3/C3aR axis during neuroretinal development. Lack of C3 or C3aR hindered the developmental phagocytic removal of astrocyte bodies and resulted in increased astrocyte density. In addition, increased astrocyte density was associated with elevated proangiogenic extracellular matrix gene expression in C3- and C3aR-deficient retinas, resulting in increased vascular density. These data demonstrate that microglia regulate developmental astrocyte and vascular network spatial patterning in the neuroretina via the complement axis.},
	keywords = {Astrocytes, Complement C3, Microglia, Retina},
	issn = {1477-9129},
	doi = {10.1242/dev.201047},
	author = {Gnanaguru, Gopalan and Tabor, Steven J and Bonilla, Gracia M and Sadreyev, Ruslan and Yuda, Kentaro and K{\"o}hl, J{\"o}rg and Connor, Kip M}
}
@article {1586181,
	title = {Targeting of miR-33 ameliorates phenotypes linked to age-related macular degeneration},
	journal = {Mol Ther},
	volume = {29},
	number = {7},
	year = {2021},
	month = {2021 Jul 07},
	pages = {2281-2293},
	abstract = {Abnormal cholesterol/lipid homeostasis is linked to neurodegenerative conditions such as age-related macular degeneration (AMD), which is a leading cause of blindness in the elderly. The most prevalent form, termed "dry" AMD, is characterized by pathological cholesterol accumulation beneath the retinal pigment epithelial (RPE) cell layer and inflammation-linked degeneration in the retina. We show here that the cholesterol-regulating microRNA miR-33 was elevated in the RPE of aging mice. Expression of the miR-33 target ATP-binding cassette transporter (ABCA1), a cholesterol efflux pump genetically linked to AMD, declined reciprocally in the RPE with age. In accord, miR-33 modulated ABCA1 expression and cholesterol efflux in human RPE cells. Subcutaneous delivery of miR-33 antisense oligonucleotides (ASO) to aging mice and non-human primates fed a Western-type high fat/cholesterol diet resulted in increased ABCA1 expression, decreased cholesterol accumulation, and reduced immune cell infiltration in the RPE cell layer, accompanied by decreased pathological changes to RPE morphology. These findings suggest that miR-33 targeting may decrease cholesterol deposition and ameliorate AMD initiation and progression.},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2021.03.014},
	author = {Gnanaguru, Gopalan and Wagschal, Alexandre and Oh, Justin and Saez-Torres, Kahira L and Li, Tong and Temel, Ryan E and Kleinman, Mark E and N{\"a}{\"a}r, Anders M and D{\textquoteright}Amore, Patricia A}
}
@article {1623368,
	title = {Discovery of sterically-hindered phenol compounds with potent cytoprotective activities against ox-LDL-induced retinal pigment epithelial cell death as a potential pharmacotherapy},
	journal = {Free Radic Biol Med},
	volume = {178},
	year = {2022},
	month = {2022 01},
	pages = {360-368},
	abstract = {Late-stage dry age-related macular degeneration (AMD) or geographic atrophy (GA) is an irreversible blinding condition characterized by degeneration of retinal pigment epithelium (RPE) and the associated photoreceptors. Clinical and genetic evidence supports a role for dysfunctional lipid processing and accumulation of harmful oxidized lipids in the pathogenesis of GA. Using an oxidized low-density lipoprotein (ox-LDL)-induced RPE death assay, we screened and identified sterically-hindered phenol compounds with potent protective activities for RPE. The phenol-containing PPARγ agonist, troglitazone, protected against ox-LDL-induced RPE cell death, whereas other more potent PPARγ agonists did not protect RPE cells. Knockdown of PPARγ did not affect the protective activity of troglitazone in RPE, confirming the protective function is not due to the thiazolidine (TZD) group of troglitazone. Prototypical hindered phenol trolox and its analogs potently protected against ox-LDL-induced RPE cell death whereas potent antioxidants without the phenol group failed to protect RPE. Hindered phenols preserved lysosomal integrity against ox-LDL-induced damage and FITC-labeled trolox was localized to the lysosomes in RPE cells. Analogs of trolox inhibited reactive oxygen species (ROS) formation induced by ox-LDL uptake in a dose-dependent fashion and were effective at sub-micromolar concentrations. Treatment with trolox analog 2,2,5,7,8-pentamethyl-6-chromanol (PMC) significantly induced the expression of the lysosomal protein NPC-1 and reduced intracellular cholesterol level upon ox-LDL uptake. Our data indicate that the lysosomal-localized hindered phenols are uniquely potent in protecting the RPE against the toxic effects of ox-LDL, and may represent a novel pharmacotherapy to preserve the vision in patients with GA.},
	keywords = {Epithelial Cells, Humans, Lipoproteins, LDL, PHENOLS, Retinal Pigment Epithelium, Retinal Pigments},
	issn = {1873-4596},
	doi = {10.1016/j.freeradbiomed.2021.11.026},
	author = {Gnanaguru, Gopalan and Mackey, Ashley and Choi, Eun Young and Arta, Anthoula and Rossato, Franco Aparecido and Gero, Thomas W and Urquhart, Andrew J and Scott, David A and D{\textquoteright}Amore, Patricia A and Ng, Yin Shan E}
}
@article {913461,
	title = {Oxidized Lipoprotein Uptake Through the CD36 Receptor Activates the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {11},
	year = {2016},
	month = {2016 Sep 1},
	pages = {4704-12},
	abstract = {PURPOSE: Accumulation of oxidized phospholipids/lipoproteins with age is suggested to contribute to the pathogenesis of AMD. We investigated the effect of oxidized LDL (ox-LDL) on human RPE cells. METHODS: Primary human fetal RPE (hf-RPE) and ARPE-19 cells were treated with different doses of LDL or ox-LDL. Assessment of cell death was measured by lactate dehydrogenase release into the conditioned media. Barrier function of RPE was assayed by measuring transepithelial resistance. Lysosomal accumulation of ox-LDL was determined by immunostaining. Expression of CD36 was determined by RT-PCR; protein blot and function was examined by receptor blocking. NLRP3 inflammasome activation was assessed by RT-PCR, protein blot, caspase-1 fluorescent probe assay, and inhibitor assays. RESULTS: Treatment with ox-LDL, but not LDL, for 48 hours caused significant increase in hf-RPE and ARPE-19 (P \&lt; 0.001) cell death. Oxidized LDL treatment of hf-RPE cells resulted in a significant decrease in transepithelial resistance (P \&lt; 0.001 at 24 hours and P \&lt; 0.01 at 48 hours) relative to LDL-treated and control cells. Internalized ox-LDL was targeted to RPE lysosomes. Uptake of ox-LDL but not LDL significantly increased CD36 protein and mRNA levels by more than 2-fold. Reverse transcription PCR, protein blot, and caspase-1 fluorescent probe assay revealed that ox-LDL treatment induced NLRP3 inflammasome when compared with LDL treatment and control. Inhibition of NLRP3 activation using 10 μM isoliquiritigenin significantly (P \&lt; 0.001) inhibited ox-LDL induced cytotoxicity. CONCLUSIONS: These data are consistent with the concept that ox-LDL play a role in the pathogenesis of AMD by NLRP3 inflammasome activation. Suppression of NLRP3 inflammasome activation could attenuate RPE degeneration and AMD progression.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18663},
	author = {Gnanaguru, Gopalan and Choi, Ariel R and Amarnani, Dhanesh and D{\textquoteright}Amore, Patricia A}
}
@article {1789151,
	title = {MNREAD Reading Vision in Adults With Glaucoma Under Mesopic and Photopic Conditions},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {15},
	year = {2023},
	month = {2023 Dec 01},
	pages = {43},
	abstract = {PURPOSE: Despite good photopic visual acuity, glaucoma patients report difficulty performing daily activities under dim light such as reading. Here we investigated the impact of mesopic lighting conditions on reading vision of glaucoma patients. METHODS: The study design included 39 patients with glaucoma and 40 healthy controls. Reading vision was assessed with MNREAD charts under mesopic (2 cd/m2) and photopic (220 cd/m2) conditions. Four reading indexes: maximum reading speed (MRS), critical print size (CPS), reading acuity (RA), and reading accessibility index (ACC) were obtained from the MNREAD test yielding a plot of reading speed versus print size. RESULTS: Compared to photopic conditions, reading vision of both healthy controls and glaucoma patients significantly decreased under mesopic conditions (P \&lt; 0.05). For glaucoma patients (85\% with mild or moderate glaucoma), MRS and ACC decreased by six words per minute and 0.1, respectively under mesopic conditions; CPS and RA increased by 0.25 and 0.18 logMAR, respectively. Moreover, under both photopic and mesopic conditions, reading vision of glaucoma patients was significantly worse than that of healthy controls, but the difference was greater under mesopic conditions (P \&lt; 0.05) even after controlling for age and visual acuity. CONCLUSIONS: Mesopic conditions make reading more challenging for both healthy controls and glaucoma patients. However, reading in dim light appears to be more burdensome for glaucoma patients. Mesopic reading tests mediated by both cone and rod photoreceptor systems likely provide a more sensitive and comprehensive assessment of a patient{\textquoteright}s reading impairment than testing under photopic conditions.},
	keywords = {Adult, Color Vision, Glaucoma, Humans, Lighting, Reading, Retinal Cone Photoreceptor Cells},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.15.43},
	author = {Goddin, Traci-Lin and Yu, Haojue and Friedman, David S and Owsley, Cynthia and Kwon, MiYoung}
}
@article {1593863,
	title = {A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome},
	journal = {Ophthalmic Genet},
	volume = {42},
	number = {5},
	year = {2021},
	month = {2021 10},
	pages = {612-614},
	abstract = {Background: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome.Patient and methods: We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking.Results: Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures.Conclusion: This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.},
	issn = {1744-5094},
	doi = {10.1080/13816810.2021.1923040},
	author = {Godfrey, Deena and Torres, Alcy and Heidary, Gena and Zahoor, Hovra and Lee, Arthur and Berry, Gerard and Engle, Elizabeth}
}
@article {1688231,
	title = {Tumor microenvironment signaling and therapeutics in cancer progression},
	journal = {Cancer Commun (Lond)},
	volume = {43},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {525-561},
	abstract = {Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss the clinical advances in the prevalent and newly discovered signaling pathways in the TME, the immune checkpoints and immunosuppressive chemokines, and currently used inhibitors targeting these pathways. These include both intrinsic and non-autonomous tumor cell signaling pathways in the TME: protein kinase C (PKC) signaling, Notch, and transforming growth factor (TGF-β) signaling, Endoplasmic Reticulum (ER) stress response, lactate signaling, Metabolic reprogramming, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and Siglec signaling pathways. We also discuss the recent advances in Programmed Cell Death Protein 1 (PD-1), Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte Activating Gene 3 (LAG3) immune checkpoint inhibitors along with the C-C chemokine receptor 4 (CCR4)- C-C class chemokines 22 (CCL22)/ and 17 (CCL17), C-C chemokine receptor type 2 (CCR2)- chemokine (C-C motif) ligand 2 (CCL2), C-C chemokine receptor type 5 (CCR5)- chemokine (C-C motif) ligand 3 (CCL3) chemokine signaling axis in the TME. In addition, this review provides a holistic understanding of the TME as we discuss the three-dimensional and microfluidic models of the TME, which are believed to recapitulate the original characteristics of the patient tumor and hence may be used as a platform to study new mechanisms and screen for various anti-cancer therapies. We further discuss the systemic influences of gut microbiota in TME reprogramming and treatment response. Overall, this review provides a comprehensive analysis of the diverse and most critical signaling pathways in the TME, highlighting the associated newest and critical preclinical and clinical studies along with their underlying biology. We highlight the importance of the most recent technologies of microfluidics and lab-on-chip models for TME research and also present an overview of extrinsic factors, such as the inhabitant human microbiome, which have the potential to modulate TME biology and drug responses.},
	keywords = {Chemokines, Humans, Neoplasms, Neoplastic Processes, Receptors, Chemokine, Signal Transduction, Tumor Microenvironment},
	issn = {2523-3548},
	doi = {10.1002/cac2.12416},
	author = {Goenka, Anshika and Khan, Fatima and Verma, Bhupender and Sinha, Priyanka and Dmello, Crismita C and Jogalekar, Manasi P and Gangadaran, Prakash and Ahn, Byeong-Cheol}
}
@article {1664955,
	title = {Characterization of Octa-aminopropyl polyhedral oligomeric silsesquioxanes (OA-POSS) nanoparticles and their effect on sweet basil (Ocimum basilicum L.) response to salinity stress},
	journal = {Plant Physiol Biochem},
	volume = {196},
	year = {2023},
	month = {2023 Jan 12},
	pages = {89-102},
	abstract = {Salt stress is of the most detrimental abiotic stress factors on either crop or non-crop species. Of the strategies employed to boost the performance of the plants against harmful impacts of salt stress; application of novel nano-engineered particles have recently gained great attention as a promising tool. Octa-aminopropyl polyhedral oligomeric silsesquioxanes nanoparticles (OA-POSS NPs) were synthesized and then a foliar-application of OA-POSS NPs were carried out on sweet basil plants subjected to the salt stress. In that context, interactive effects of OA-POSS NPs (25, 50 and 100\&nbsp;mg\&nbsp;L-1) and salinity stress (50 and 100\&nbsp;mM NaCl) were assayed by estimating a series of agronomic, physiological, biochemical and analytical parameters. OA-POSS NPs decreased the harmful effects of salinity by increasing photosynthetic pigment content, adjusting chlorophyll fluorescence, and triggering non-enzymatic (phenolic content) and enzymatic antioxidant components. The findings suggested that 25\&nbsp;mg\&nbsp;L-1 OA-POSS NPs is the optimum concentration for sweet basil grown under salt stress. Considering the essential oil profile, estragole was the predominant compound with a percentage higher than 50\% depending on the treatment. In comparison to the control group, 50\&nbsp;mM NaCl did not significantly affect estragole content, whilst 100\&nbsp;mM NaCl caused a substantial increase in estragole content. Regarding OA-POSS NPs treatments, increments by 16.8\%, 11.8\% and 17.5\% were observed following application with 25, 50 and 100\&nbsp;mg\&nbsp;L-1, respectively. Taken together, the current study provides evidence that POSS NPs can be employed as novel, {\textquoteright}green{\textquoteright} growth promoting agents in combating salt stress in sweet basil.},
	issn = {1873-2690},
	doi = {10.1016/j.plaphy.2023.01.019},
	author = {Gohari, Gholamreza and Panahirad, Sima and Mohammadi, Asghar and Kulak, Muhittin and Dadpour, Mohamad Reza and Lighvan, Zohreh Mehri and Sharifi, Sina and Eftekhari-Sis, Bagher and Szafert, S{\l}awomir and Fotopoulos, Vasileios and Akbari, Ali}
}
@article {1517173,
	title = {Lacrimal tissue resection in Fasanella Servat operation and the correlation to dry eye},
	journal = {Orbit},
	volume = {39},
	number = {3},
	year = {2020},
	month = {2020 Jun},
	pages = {171-174},
	abstract = {: Fasanella-Servat operation (FSO) was previously reported to be associated with post-operative dry eyes due to accessory lacrimal gland resection during the surgery.We performed a retrospective, cohort study to determine the frequency of lacrimal tissue resection during FSO and its correlation with post-operative eye dryness and keratopathy.: Review of all patients who underwent FSO at New York-Presbyterian Weill Cornell Hospital over a two-year period (2013-2015). Patients were included only if they had adequate histopathological specimens of the resected tissue obtained during surgery. Outcomes included the study of the pathological specimen for the presence of lacrimal tissue; Post-operative dry eye symptoms and pre- and post-operative corneal epitheliopathy.: 46 patients with a total of 58 eyelid resections were studied.Eight eyelids (13.7\%) were found to have lacrimal tissue present in the pathology specimens.Postoperatively, nine patients reported some symptoms of dry eye and new-onset keratopathy was noted in four eyes (6.8\%), only one of which had lacrimal tissue present in histopathology specimen obtained from surgery.: Previous studies found lacrimal tissue present in up to 43\% of specimens resected during FSO. Our data found a lower rate of lacrimal tissue resection during FSO, and did not find an association between lacrimal tissue resection and post-operative dryness or epitheliopathy.: Our study is one of few to examine histopathological resections from the FSO.We found that lacrimal tissue is not frequently resected during FSO, and when it is resected, there is no increased incidence of post-operative dryness or keratopathy.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2019.1649435},
	author = {Golan, Shani and Vingopoulos, Filippos and Olson, Luke C and Patel, Hency H and Pinchover, Shulamit and Magro, Cynthia M and Levine, Benjamin and Lelli, Gary J}
}
@article {1698281,
	title = {Perspectives of Rare Disease Experts on Newborn Genome Sequencing},
	journal = {JAMA Netw Open},
	volume = {6},
	number = {5},
	year = {2023},
	month = {2023 May 01},
	pages = {e2312231},
	abstract = {IMPORTANCE: Newborn genome sequencing (NBSeq) can detect infants at risk for treatable disorders currently undetected by conventional newborn screening. Despite broad stakeholder support for NBSeq, the perspectives of rare disease experts regarding which diseases should be screened have not been ascertained. OBJECTIVE: To query rare disease experts about their perspectives on NBSeq and which gene-disease pairs they consider appropriate to evaluate in apparently healthy newborns. DESIGN, SETTING, AND PARTICIPANTS: This survey study, designed between November 2, 2021, and February 11, 2022, assessed experts{\textquoteright} perspectives on 6 statements related to NBSeq. Experts were also asked to indicate whether they would recommend including each of 649 gene-disease pairs associated with potentially treatable conditions in NBSeq. The survey was administered between February 11 and September 23, 2022, to 386 experts, including all 144 directors of accredited medical and laboratory genetics training programs in the US. EXPOSURES: Expert perspectives on newborn screening using genome sequencing. MAIN OUTCOMES AND MEASURES: The proportion of experts indicating agreement or disagreement with each survey statement and those who selected inclusion of each gene-disease pair were tabulated. Exploratory analyses of responses by gender and age were conducted using t and χ2 tests. RESULTS: Of 386 experts invited, 238 (61.7\%) responded (mean [SD] age, 52.6 [12.8] years [range 27-93 years]; 126 [52.9\%] women and 112 [47.1\%] men). Among the experts who responded, 161 (87.9\%) agreed that NBSeq for monogenic treatable disorders should be made available to all newborns; 107 (58.5\%) agreed that NBSeq should include genes associated with treatable disorders, even if those conditions were low penetrance; 68 (37.2\%) agreed that actionable adult-onset conditions should be sequenced in newborns to facilitate cascade testing in parents, and 51 (27.9\%) agreed that NBSeq should include screening for conditions with no established therapies or management guidelines. The following 25 genes were recommended by 85\% or more of the experts: OTC, G6PC, SLC37A4, CYP11B1, ARSB, F8, F9, SLC2A1, CYP17A1, RB1, IDS, GUSB, DMD, GLUD1, CYP11A1, GALNS, CPS1, PLPBP, ALDH7A1, SLC26A3, SLC25A15, SMPD1, GATM, SLC7A7, and NAGS. Including these, 42 gene-disease pairs were endorsed by at least 80\% of experts, and 432 genes were endorsed by at least 50\% of experts. CONCLUSIONS AND RELEVANCE: In this survey study, rare disease experts broadly supported NBSeq for treatable conditions and demonstrated substantial concordance regarding the inclusion of a specific subset of genes in NBSeq.},
	keywords = {Adult, Aged, Aged, 80 and over, Amino Acid Transport System y+L, Antiporters, Chondroitinsulfatases, Female, Humans, Infant, Newborn, Male, Middle Aged, Monosaccharide Transport Proteins, Neonatal Screening, Parents, Rare Diseases},
	issn = {2574-3805},
	doi = {10.1001/jamanetworkopen.2023.12231},
	author = {Gold, Nina B and Adelson, Sophia M and Shah, Nidhi and Williams, Shardae and Bick, Sarah L and Zoltick, Emilie S and Gold, Jessica I and Strong, Alanna and Ganetzky, Rebecca and Roberts, Amy E and Walker, Melissa and Holtz, Alexander M and Sankaran, Vijay G and Delmonte, Ottavia and Tan, Weizhen and Holm, Ingrid A and Thiagarajah, Jay R and Kamihara, Junne and Comander, Jason and Place, Emily and Wiggs, Janey and Green, Robert C}
}
@article {1435401,
	title = {In Situ Modification of Tissue Stem and Progenitor Cell Genomes},
	journal = {Cell Rep},
	volume = {27},
	number = {4},
	year = {2019},
	month = {2019 Apr 23},
	pages = {1254-1264.e7},
	abstract = {In\&nbsp;vivo delivery of genome-modifying enzymes holds significant promise for therapeutic applications and functional genetic screening. Delivery to endogenous tissue stem cells, which provide an enduring source of cell replacement during homeostasis and regeneration, is of particular interest. Here, we use a sensitive Cre/lox fluorescent reporter system to test the efficiency of genome modification following in\&nbsp;vivo transduction by adeno-associated viruses (AAVs) in tissue stem and progenitor cells. We combine immunophenotypic analyses with in\&nbsp;vitro and in\&nbsp;vivo assays of stem cell function to reveal effective targeting of skeletal muscle satellite cells,\&nbsp;mesenchymal progenitors, hematopoietic stem cells, and dermal cell subsets using multiple AAV serotypes. Genome modification rates achieved through this system reached \&gt;60\%, and modified cells retained key functional properties. This study establishes a powerful platform to genetically alter tissue progenitors within their physiological niche while preserving their native stem cell properties and regulatory interactions.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2019.03.105},
	author = {Goldstein, Jill M and Tabebordbar, Mohammadsharif and Zhu, Kexian and Wang, Leo D and Messemer, Kathleen A and Peacker, Bryan and Ashrafi Kakhki, Sara and Meryem Gonzalez-Celeiro and Shwartz, Yulia and Cheng, Jason K W and Xiao, Ru and Barungi, Trisha and Albright, Charles and Ya-Chieh Hsu and Vandenberghe, Luk H and Wagers, Amy J}
}
@article {1677671,
	title = {Visual Acuity: Assessment of Data Quality and Usability in an Electronic Health Record System},
	journal = {Ophthalmol Sci},
	volume = {3},
	number = {1},
	year = {2023},
	month = {2023 Mar},
	pages = {100215},
	abstract = {OBJECTIVE: To examine the data quality and usability of visual acuity (VA) data extracted from an electronic health record (EHR) system during ophthalmology encounters and provide recommendations for consideration of relevant VA end points in retrospective analyses. DESIGN: Retrospective, EHR data analysis. PARTICIPANTS: All patients with eyecare office encounters at any 1 of the 9 locations of a large academic medical center between August 1, 2013, and December 31,\&nbsp;2015. METHODS: Data from 13 of the 21 VA fields (accounting for 93\% VA data) in EHR encounters were extracted, categorized, recoded, and assessed for conformance and plausibility using an internal data dictionary, a 38-item listing of VA line measurements and observations including 28 line measurements (e.g., 20/30, 20/400) and 10 observations (e.g., no light perception). Entries were classified into usable and unusable data. Usable data were further categorized based on conformance to the internal data dictionary: (1) exact match; (2) conditional conformance, letter count (e.g., 20/30+2 - 3); (3) convertible conformance (e.g., 5/200 to 20/800); (4) plausible but cannot be conformed (e.g., 5/400). Data were deemed unusable when they were not plausible. MAIN OUTCOME MEASURES: Proportions of usable and unusable VA entries at the overall and subspecialty levels. RESULTS: All VA data from 513 036 encounters representing 166 212 patients were included. Of the 1 573 643 VA entries, 1 438 661 (91.4\%) contained usable data. There were 1 196 720 (76.0\%) exact match (category 1), 185 692 (11.8\%) conditional conformance (category 2), 40 270 (2.6\%) convertible conformance (category 3), and 15\&nbsp;979 (1.0\%) plausible but not conformed entries (category 4). Visual acuity entries during visits with providers from retina (17.5\%), glaucoma (14.0\%), neuro-ophthalmology (8.9\%), and low vision (8.8\%) had the highest rates of unusable data. Documented VA entries with providers from comprehensive eyecare (86.7\%), oculoplastics (81.5\%), and pediatrics/strabismus (78.6\%) yielded the highest proportions of exact match with the data dictionary. CONCLUSIONS: Electronic health record VA data quality and usability vary across documented VA measures, observations, and eyecare subspecialty. We proposed a checklist of considerations and recommendations for planning, extracting, analyzing, and reporting retrospective study outcomes using EHR VA data. These are important first steps to standardize analyses enabling comparative research.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100215},
	author = {Goldstein, Judith E and Guo, Xinxing and Boland, Michael V and Smith, Kerry E}
}
@article {416916,
	title = {Clinically Meaningful Rehabilitation Outcomes of Low Vision Patients Served by Outpatient Clinical Centers.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {7},
	year = {2015},
	month = {2015 Jul 1},
	pages = {762-9},
	abstract = {IMPORTANCE: To facilitate comparative clinical outcome research in low vision rehabilitation, we must use patient-centered measurements that reflect clinically meaningful changes in visual ability. OBJECTIVE: To quantify the effects of currently provided low vision rehabilitation (LVR) on patients who present for outpatient LVR services in the United States. DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational study of new patients seeking outpatient LVR services. From April 2008 through May 2011, 779 patients from 28 clinical centers in the United States were enrolled in the Low Vision Rehabilitation Outcomes Study. The Activity Inventory, a visual function questionnaire, was administered to measure overall visual ability and visual ability in 4 functional domains (reading, mobility, visual motor function, and visual information processing) at baseline and 6 to 9 months after usual LVR care. The Geriatric Depression Scale, Telephone Interview for Cognitive Status, and Medical Outcomes Study 36-Item Short-Form Health Survey physical functioning questionnaires were also administered to measure patients{\textquoteright} psychological, cognitive, and physical health states, respectively, and clinical findings of patients were provided by study centers. MAIN OUTCOMES AND MEASURES: Mean changes in the study population and minimum clinically important differences in the individual in overall visual ability and in visual ability in 4 functional domains as measured by the Activity Inventory. RESULTS: Baseline and post-rehabilitation measures were obtained for 468 patients. Minimum clinically important differences (95\% CIs) were observed in nearly half (47\% [95\% CI, 44\%-50\%]) of patients in overall visual ability. The prevalence rates of patients with minimum clinically important differences in visual ability in functional domains were reading (44\% [95\% CI, 42\%-48\%]), visual motor function (38\% [95\% CI, 36\%-42\%]), visual information processing (33\% [95\% CI, 31\%-37\%]), and mobility (27\% [95\% CI, 25\%-31\%]). The largest average effect size (Cohen d = 0.87) for the population was observed in overall visual ability. Age (P = .006) was an independent predictor of changes in overall visual ability, and logMAR visual acuity (P = .002) was predictive of changes in visual information processing. CONCLUSIONS AND RELEVANCE: Forty-four to fifty percent of patients presenting for outpatient LVR show clinically meaningful differences in overall visual ability after LVR, and the average effect sizes in overall visual ability are large, close to 1 SD.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.0693},
	author = {Goldstein, Judith E and Jackson, Mary Lou and Fox, Sandra M and Deremeik, James T and Massof, Robert W and Low Vision Research Network Study Group}
}
@article {1655730,
	title = {Using Electronic Clinical Decision Support to Examine Vision Rehabilitation Referrals and Practice Guidelines in Ophthalmology},
	journal = {Transl Vis Sci Technol},
	volume = {11},
	number = {10},
	year = {2022},
	month = {2022 10 03},
	pages = {8},
	abstract = {Purpose: To examine ophthalmologist use of an electronic health record (EHR)-based clinical decision support system (CDSS) to facilitate low vision rehabilitation (LVR) care referral. Methods: The CDSS alert was designed to appear when best documented visual acuity was \&lt;20/40 or hemianopia or quadrantanopia diagnosis was identified during an ophthalmology encounter from November 6, 2017, to April 5, 2019. Fifteen ophthalmologists representing eight subspecialties from an academic medical center were required to respond to the referral recommendation (order, don{\textquoteright}t order). LVR referral rates and ophthalmologist user experience were assessed. Encounter characteristics associated with LVR referrals were explored using multilevel logistic regression analysis. Results: The alert appeared for 3625 (8.9\%) of 40,931 eligible encounters. The referral rate was 14.8\% (535/3625). Of the 3413 encounters that met the visual acuity criterion only, patients who were worse than 20/60 were more likely to be referred, and 32.4\% of referred patients were between 20/40 and 20/60. Primary reasons for deferring referrals included active medical or surgical treatment, refractive-related issues, and previous connection to LVR services. Eleven of the 13 ophthalmologists agreed that the alert was useful in identifying candidates for LVR services. Conclusions: A CDSS for patient identification and referral offers an acceptable mechanism to apply practice guidelines and prompt ophthalmologists to facilitate LVR care. Further study is warranted to optimize ophthalmologist user experience while refining alert criteria beyond visual acuity. Translational Relevance: The CDSS provides the framework for multi-center research to assess the development of pragmatic algorithms and standards for facilitating LVR care.},
	keywords = {Decision Support Systems, Clinical, Electronics, Humans, Ophthalmology, Referral and Consultation, Vision, Low},
	issn = {2164-2591},
	doi = {10.1167/tvst.11.10.8},
	author = {Goldstein, Judith E and Guo, Xinxing and Swenor, Bonnielin K and Boland, Michael V and Smith, Kerry}
}
@article {1364607,
	title = {Therapeutic interventions against inflammatory and angiogenic mediators in proliferative diabetic retinopathy},
	journal = {Mediators Inflamm},
	volume = {2012},
	year = {2012},
	month = {2012},
	pages = {629452},
	abstract = {The global prevalence of diabetes is estimated to be 336 million people, with diabetic complications contributing to significant worldwide morbidity and mortality. Diabetic retinopathy results from cumulative microvascular damage to the retina and inflammation is recognized as a critical driver of this disease process. This paper outlines the pathophysiology leading to proliferative diabetic retinopathy and highlights many of the inflammatory, angiogenic, and cytokine mediators implicated in the development and progression of this disease. We focus a detailed discussion on the current targeted therapeutic interventions used to treat diabetic retinopathy.},
	keywords = {Cytokines, Diabetic Retinopathy, Humans, Inflammation, Vascular Endothelial Growth Factor A},
	issn = {1466-1861},
	doi = {10.1155/2012/629452},
	author = {Gologorsky, Daniel and Thanos, Aristomenis and Vavvas, Demetrios}
}
@article {1635647,
	title = {Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study},
	journal = {J Investig Allergol Clin Immunol},
	volume = {33},
	number = {4},
	year = {2023},
	month = {2023 Jul 27},
	pages = {271-280},
	abstract = {BACKGROUND AND OBJECTIVE: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. METHODS: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2\%, 0.4\%, and 0.6\%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. RESULTS: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2\%, 0.4\%, and 0.6\% were significantly superior (P\&gt;.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6\% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6\% were statistically significant (P\&lt;.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. CONCLUSION: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6\% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated.},
	keywords = {Adult, Anti-Allergic Agents, Benzimidazoles, Conjunctivitis, Allergic, Double-Blind Method, Humans, Ophthalmic Solutions, Piperidines, Pruritus},
	issn = {1018-9068},
	doi = {10.18176/jiaci.0800},
	author = {Gomes, P J and Ciolino, J. B. and Arranz, P and Hern{\'a}ndez, G and Fern{\'a}ndez, N}
}
@article {1761996,
	title = {Bilastine 0.6\% preservative-free eye drops, an effective once-daily treatment to reduce signs and symptoms of allergic conjunctivitis: A pooled analysis of two randomized clinical trials},
	journal = {J Investig Allergol Clin Immunol},
	year = {2023},
	month = {2023 Sep 21},
	abstract = {BACKGROUND AND OBJECTIVE: Allergic conjunctivitis is the most common type of ocular allergy. The objective of this study was to evaluate the efficacy of a new once-daily, preservative-free, bilastine 0.6\% eye drop formulation for the treatment of allergic conjunctivitis. METHODS: Two double-masked, vehicle controlled, clinical studies (a Phase 2 Dose Ranging Study and a Phase 3 Efficacy Study) were conducted to assess the efficacy of bilastine ophthalmic solution for the treatment of signs and symptoms of allergic conjunctivitis. Both studies used the Ora-CAC{\textregistered} Conjunctival Allergen Challenge (CAC) Model to allow observations of allergic responses under controlled conditions. Each study was analyzed separately and then combined to create an integrated dataset. RESULTS: Efficacy was achieved for the primary efficacy endpoint of ocular itching for three bilastine concentrations (0.2\%, 0.4\%, and 0.6\%) at 15 minutes and 8 hours post-instillation and bilastine 0.6\% ophthalmic solution was also efficacious at 16 hours post-instillation. Bilastine 0.6\% ophthalmic solution demonstrated non-inferiority to ketotifen 0.025\% at the onset of action. From the integrated data set, differences between vehicle and bilastine 0.6\% were significant at all time points both at onset (15 minutes) and at a prolonged duration (16 hours) after instillation. CONCLUSION: This multi-trial assessment suggests that bilastine 0.6\% ophthalmic solution is efficacious for the treatment of the signs and symptoms of allergic conjunctivitis, with a rapid and prolonged duration of action, and has a favorable safety profile. The added convenience of a once-a-day dosing regimen may contribute to patient adherence and improve their quality of life.},
	issn = {1018-9068},
	doi = {10.18176/jiaci.0940},
	author = {Gomes, P J and Ciolino, J. B. and Arranz, P and Gonzalo, A and Fern{\'a}ndez, N and Hern{\'a}ndez, G}
}
@article {961701,
	title = {Technical and clinical validation of an environmental exposure unit for ragweed.},
	journal = {J Asthma Allergy},
	volume = {9},
	year = {2016},
	month = {2016},
	pages = {215-221},
	abstract = {BACKGROUND: Allergic rhinitis is a common condition, with ragweed pollen one of the more prevalent aeroallergens. Environmental exposure units such as the Allergen BioCube({\textregistered}) are valuable models for clinical allergy studies. A study was conducted to validate the Allergen BioCube for uniform ragweed pollen concentrations and clinically relevant sign and symptom responses to ragweed exposure. METHODS: Ragweed pollen concentrations were measured on 3 consecutive days in the Allergen BioCube and verified by Rotorod collection and continuous laser particle count measurements. Subjects (N=10) were exposed to ragweed pollen in the BioCube for 3 hours per day for 3 consecutive days. Subjects assessed their nasal itching, sneezing, rhinorrhea, and nasal congestion during each BioCube exposure; total nasal symptom score was computed. Peak nasal inspiratory flow was also assessed during BioCube exposure. RESULTS: Uniform ragweed pollen concentrations were obtained throughout each of the 3-hour testing periods in the Allergen BioCube, both spatially and temporally, at all subject positions, with a low mean standard deviation of 10\%. Pronounced increases in mean total nasal symptom scores (6.7{\textpm}0.94 to 7.6{\textpm}0.86, last 90 minutes of exposure) occurred for all three BioCube ragweed pollen exposure visits. Mean peak nasal inspiratory flow decreased 24\% at 3 hours of BioCube exposure on Day 3. No safety issues of concern occurred in this study. CONCLUSION: The Allergen BioCube achieved technical and clinical validation for ragweed allergen. Ragweed pollen concentration was uniform both temporally and spatially. Allergic rhinitis signs and symptoms were induced in subjects during exposure to ragweed in the BioCube at clinically meaningful levels for allergy studies.},
	doi = {10.2147/JAA.S123547},
	author = {Gomes, Paul J and Lane, Keith J and Angjeli, Endri and Stein, Linda and Abelson, Mark B}
}
@article {1430527,
	title = {Iodixanol nasal solution reduces allergic rhinoconjunctivitis signs and symptoms in Allergen BioCube: a randomized clinical trial},
	journal = {J Asthma Allergy},
	volume = {12},
	year = {2019},
	month = {2019},
	pages = {71-81},
	abstract = {Purpose: Allergic rhinitis (AR) affects ~20\% of the population worldwide. The objectives of this study were to evaluate the safety and efficacy of iodixanol nasal solution (Nasapaque) for AR treatment, using the Allergen BioCube (ABC), an environmental exposure unit. Iodixanol is a commonly used contrast media agent that shows efficacy on the signs and symptoms of AR. Patients and methods: Seventy-three adult subjects with AR were randomized to iodixanol or placebo treatment in a double-masked efficacy and safety study conducted outside of ragweed pollen season. In-office treatment was administered after BioCube ragweed pollen exposure, and again 8 days later prior to ragweed exposure. Nasal and ocular efficacy and safety assessments were conducted before and after treatment. Results: Iodixanol treatment resulted in statistically significantly lower total nasal symptom scores as compared to placebo at several time points post-treatment and ABC exposure. Individual nasal and ocular symptoms, notably nasal itching and ocular itching, showed evidence of lower scores in the iodixanol group. Peak nasal inspiratory flow (PNIF) improved (9\%-16\%) with iodixanol from baseline as compared to PNIF in the placebo group which ranged from 3\% worsening to improvement of 2\%. Few (9) adverse events occurred. Conclusion: Iodixanol nasal solution demonstrated efficacy for relief of several nasal and ocular allergic rhinoconjunctivitis signs and symptoms, and was safe and well tolerated in this early Phase II exploratory trial. Further studies with iodixanol are warranted. Allergy challenge models such as the ABC provide valuable assessments of allergen exposures and drug efficacies. Study Identification Number: NCT02377895.},
	issn = {1178-6965},
	doi = {10.2147/JAA.S150251},
	author = {Gomes, Paul J and Abelson, Mark B and Stein, Linda and Viirre, Erik and Villafranca, J Ernest and Lasser, Elliott C}
}
@article {1667704,
	title = {Bilastine 0.6\% preservative-free eye drops, a once-daily treatment for allergic conjunctivitis},
	journal = {J Investig Allergol Clin Immunol},
	year = {2023},
	month = {2023 Feb 21},
	abstract = {BACKGROUND: Bilastine is a second-generation antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. This trial evaluated the efficacy and safety of a new bilastine 0.6\% preservative-free eye-drops formulation for the symptomatic treatment of allergic conjunctivitis. METHODS: This phase 3, multicenter, double-masked, randomized study evaluated the efficacy, safety and tolerability of bilastine 0.6\% ophthalmic solution compared to ketotifen 0.025\% and vehicle. The primary efficacy endpoint was ocular itching reduction. The Ora-CAC{\textregistered} Allergen Challenge Model was used to assess ocular and nasal symptoms at 15 minutes (onset of action) and 16 hours post-treatment. RESULTS: Subjects (N=228) were 59.6\% male, and the mean (SD) age was 44.1 (13.4) years. Bilastine demonstrated efficacy in reducing ocular itching compared to vehicle at both onset of action and 16 hours post-treatment (P \&lt;0.001). Ketotifen showed improvement compared to vehicle 15 minutes post-treatment (P \&lt;0.001). Bilastine demonstrated statistical non-inferiority to ketotifen for all 3 post-CAC timepoints at 15 minutes post-instillation, based on an inferiority margin of 0.4. Bilastine demonstrated improvement over vehicle (P \&lt;0.05) for conjunctival redness, ciliary redness, episcleral redness, chemosis, eyelid swelling, tearing, rhinorrhea, ear and palate pruritus and nasal congestion at 15 minutes post-treatment. Ophthalmic bilastine was safe and well tolerated. Mean drop comfort scores were significantly better (P \&lt;0.05) for bilastine compared with ketotifen immediately upon instillation, and similar compared with vehicle. CONCLUSIONS: Ophthalmic bilastine effectively reduced ocular itching for 16 hours post-treatment, suggesting that it could be used as a once-daily treatment for the signs and symptoms of allergic conjunctivitis. ClinicalTrials.gov identifier: NCT03479307.},
	issn = {1018-9068},
	doi = {10.18176/jiaci.0894},
	author = {Gomes, P J and Ciolino, J. B. and Arranz, P and Hern{\'a}ndez, G and Fern{\'a}ndez, N}
}
@article {1647894,
	title = {Brief incubation of corneal grafts in activated platelet rich plasma enhances corneal endothelial cell survival and regeneration},
	journal = {Exp Eye Res},
	volume = {220},
	year = {2022},
	month = {2022 Jul},
	pages = {109100},
	abstract = {Corneal transplantation is the most frequent organ transplantation worldwide. Unfortunately, corneal graft failure is common and endothelial decompensation is considered the major cause. Corneal endothelial cells (CECs) lack the capacity to reproduce, and perioperative and postoperative endothelial cell loss remains a significant challenge associated with corneal graft viability. Therefore, strategies to preserve CEC density are critical to extend graft survival. Activated platelet rich plasma (aPRP), a product extracted from autologous blood, has both antioxidant and regenerative properties. aPRP eye drops have shown effectiveness in the treatment of corneal pathologies such as ulcers, dry eye, and burns. Our purpose is to determine the protective and regenerative effect of aPRP on corneal grafts by evaluating aPRP{\textquoteright}s effect on the survival and proliferation of human CECs. Human corneal grafts were incubated in aPRP for 15\&nbsp;min to assess the activation of the CEC pAkt survival pathway as measured by ELISA. Evaluation of the protective effect of aPRP was made using an apoptotic model, which simulated oxidative stress conditions. Expression of apoptotic markers was measured using ELISA and endothelial cell viability was determined by optical microscopy. The CEC proliferation rate was measured in vitro with Ki-67 staining. Corneal graft gross structure was evaluated by Hematoxylin \&amp; Eosin and Masson trichrome staining. Our results indicate that a short incubation of human corneal grafts in aPRP protects CECs from apoptosis by upregulating the pAkt survival pathway and promoting CEC proliferation. Additionally, aPRP incubation does not induce histological changes in the grafts. A brief pre-treatment of human corneal grafts in aPRP may be beneficial for transplant longevity, as it protects CECs from apoptosis by upregulating intracellular survival pathways and promoting proliferation. In addition, this approach appears to be safe and has the potential to improve surgical outcomes following corneal transplantation.},
	keywords = {Corneal Transplantation, Endothelial Cells, Endothelium, Corneal, Humans, Platelet-Rich Plasma, Regeneration},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2022.109100},
	author = {Gomez, Angela and Mercado, Carolina and Venkateswaran, Nandini and Sen-Corcuera, Borja de la and Miller, Darlene and Dubovy, Sander and Salero, Enrique and Sabater, Alfonso L}
}
@article {836851,
	title = {Bottom-Up and Top-Down Input Augment the Variability of Cortical Neurons.},
	journal = {Neuron},
	volume = {91},
	number = {3},
	year = {2016},
	month = {2016 Aug 3},
	pages = {540-7},
	abstract = {Neurons in the cerebral cortex respond inconsistently to a repeated sensory stimulus, yet they underlie our stable sensory experiences. Although the nature of this variability is unknown, its ubiquity has encouraged the general view that each cell produces random spike patterns that noisily represent its response rate. In contrast, here we show that reversibly inactivating distant sources of either bottom-up or top-down input to cortical visual areas in the alert primate reduces both the spike train irregularity and the trial-to-trial variability of single neurons. A simple model in which a fraction of the pre-synaptic input is silenced can reproduce this reduction in variability, provided that there exist temporal correlations primarily within, but not between, excitatory and inhibitory input pools. A large component of the variability of cortical neurons may therefore arise from synchronous input produced by signals arriving from multiple sources.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2016.06.028},
	author = {G{\'o}mez-Laberge, Camille and Smolyanskaya, Alexandra and Nassi, Jonathan J and Kreiman, Gabriel and Born, Richard T}
}
@article {1580497,
	title = {Application of Deep Learning for Diagnosing, Classifying, and Treating Age-Related Macular Degeneration},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {198-204},
	abstract = {Age-related macular degeneration (AMD) affects nearly 200 million people and is the third leading cause of irreversible vision loss worldwide. Deep learning, a branch of artificial intelligence that can learn image recognition based on pre-existing datasets, creates an opportunity for more accurate and efficient diagnosis, classification, and treatment of AMD on both individual and population levels. Current algorithms based on fundus photography and optical coherence tomography imaging have already achieved diagnostic accuracy levels comparable to human graders. This accuracy can be further increased when deep learning algorithms are simultaneously applied to multiple diagnostic imaging modalities. Combined with advances in telemedicine and imaging technology, deep learning can enable large populations of patients to be screened than would otherwise be possible and allow ophthalmologists to focus on seeing those patients who are in need of treatment, thus reducing the number of patients with significant visual impairment from AMD.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1889617},
	author = {Gong, Dan and Kras, Ashley and Miller, John B}
}
@article {1078741,
	title = {ω-3 and ω-6 long-chain PUFAs and their enzymatic metabolites in neovascular eye diseases},
	journal = {Am J Clin Nutr},
	volume = {106},
	number = {1},
	year = {2017},
	month = {2017 Jul},
	pages = {16-26},
	abstract = {Neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, threaten the visual health of children and adults. Current treatment options, including anti-vascular endothelial growth factor therapy and laser retinal photocoagulation, have limitations and are associated with adverse effects; therefore, the identification of additional therapies is highly desirable. Both clinical and experimental studies show that dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) reduce retinal and choroidal angiogenesis. The ω-3 LC-PUFA metabolites from 2 groups of enzymes, cyclooxygenases and lipoxygenases, inhibit [and the ω-6 (n-6) LC-PUFA metabolites promote] inflammation and angiogenesis. However, both of the ω-3 and the ω-6 lipid products of cytochrome P450 oxidase 2C promote neovascularization in both the retina and choroid, which suggests that inhibition of this pathway might be beneficial. This review summarizes our current understanding of the roles of ω-3 and ω-6 LC-PUFAs and their enzymatic metabolites in neovascular eye diseases.},
	issn = {1938-3207},
	doi = {10.3945/ajcn.117.153825},
	author = {Gong, Yan and Fu, Zhongjie and Liegl, Raffael and Chen, Jing and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {836841,
	title = {Cytochrome P450 Oxidase 2C Inhibition Adds to ω-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization.},
	journal = {Arterioscler Thromb Vasc Biol},
	volume = {36},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1919-27},
	abstract = {OBJECTIVE: Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but ω-3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of ω-3 LCPUFA on neovascular eye diseases. APPROACH AND RESULTS: The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of ω-3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and ω-3 LCPUFA-derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of ω-3 LCPUFA on retinal neovascularization and CNV by 30\% and 20\%, respectively. In CYP2C8-overexpressing mice fed a ω-3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36\% and 39\% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C ω-3 LCPUFA-derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected ω-3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. CONCLUSIONS: Inhibition of CYP2C activity adds to the protective effects of ω-3 LCPUFA on pathological retinal neovascularization and CNV.},
	issn = {1524-4636},
	doi = {10.1161/ATVBAHA.116.307558},
	author = {Gong, Yan and Fu, Zhongjie and Edin, Matthew L and Liu, Chi-Hsiu and Wang, Zhongxiao and Shao, Zhuo and Fredrick, Thomas W and Saba, Nicholas J and Morss, Peyton C and Burnim, Samuel B and Meng, Steven S and Lih, Fred B and Stephen Lee, Kin Sing and Moran, Elizabeth P and SanGiovanni, John Paul and Hellstr{\"o}m, Ann and Hammock, Bruce D and Zeldin, Darryl C and Smith, Lois E H}
}
@article {1647878,
	title = {Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice},
	journal = {Metabolism},
	volume = {134},
	year = {2022},
	month = {2022 09},
	pages = {155266},
	abstract = {INTRODUCTION: Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) leads to blindness. It has been widely reported that increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) diets reduce CNV. Of the three major pathways metabolizing ω-3 (and ω-6 LCPUFA), the cyclooxygenase and lipoxygenase pathways generally produce pro-angiogenic metabolites from ω-6 LCPUFA and anti-angiogenic ones from ω-3 LCPUFA. Howevehr, cytochrome P450 oxidase (CPY) 2C produces pro-angiogenic metabolites from both ω-6 and ω-3 LCPUFA. The effects of CYP2J2 products on ocular neovascularization are still unknown. Understanding how each metabolic pathway affects the protective effect of ω-3 LCPUFA on retinal neovascularization may lead to therapeutic interventions. OBJECTIVES: To investigate the effects of LCPUFA metabolites through CYP2J2 pathway and CYP2J2 regulation on CNV both in vivo and ex vivo. METHODS: The impact of CYP2J2 overexpression and inhibition on neovascularization in the laser-induced CNV mouse model was assessed. The plasma levels of CYP2J2 metabolites were measured by liquid chromatography and tandem mass spectroscopy. The choroidal explant sprouting assay was used to investigate the effects of CYP2J2 inhibition and specific LCPUFA CYP2J2 metabolites on angiogenesis ex vivo. RESULTS: CNV was exacerbated in Tie2-Cre CYP2J2-overexpressing mice and was associated with increased levels of plasma docosahexaenoic acids. Inhibiting CYP2J2 activity with flunarizine decreased CNV in both ω-6 and ω-3 LCPUFA-fed wild-type mice. In Tie2-Cre CYP2J2-overexpressing mice, flunarizine suppressed CNV by 33 \% and 36 \% in ω-6, ω-3 LCPUFA diets, respectively, and reduced plasma levels of CYP2J2 metabolites. The pro-angiogenic role of CYP2J2 was corroborated in the choroidal explant sprouting assay. Flunarizine attenuated ex vivo choroidal sprouting, and 19,20-EDP, a ω-3 LCPUFA CYP2J2 metabolite, increased sprouting. The combined inhibition of CYP2J2 with flunarizine and CYP2C8 with montelukast further enhanced CNV suppression via tumor necrosis factor-α suppression. CONCLUSIONS: CYP2J2 inhibition augmented the inhibitory effect of ω-3 LCPUFA on CNV. Flunarizine suppressed pathological choroidal angiogenesis, and co-treatment with montelukast inhibiting CYP2C8 further enhanced the effect. CYP2 inhibition might be a viable approach to suppress CNV in AMD.},
	keywords = {Animals, Choroidal Neovascularization, Cytochrome P-450 CYP2C8, Disease Models, Animal, Docosahexaenoic Acids, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Flunarizine, Macular Degeneration, Mice, Mice, Inbred C57BL, NADPH-Ferrihemoprotein Reductase},
	issn = {1532-8600},
	doi = {10.1016/j.metabol.2022.155266},
	author = {Gong, Yan and Tomita, Yohei and Edin, Matthew L and Ren, Anli and Ko, Minji and Yang, Jay and Bull, Edward and Zeldin, Darryl C and Hellstr{\"o}m, Ann and Fu, Zhongjie and Smith, Lois E H}
}
@article {504026,
	title = {Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice.},
	journal = {PLoS One},
	volume = {10},
	number = {7},
	year = {2015},
	month = {2015},
	pages = {e0132643},
	abstract = {The mouse model of laser-induced choroidal neovascularization (CNV) has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0132643},
	author = {Gong, Yan and Li, Jie and Sun, Ye and Fu, Zhongjie and Liu, Chi-Hsiu and Evans, Lucy and Tian, Katherine and Saba, Nicholas and Fredrick, Thomas and Morss, Peyton and Chen, Jing and Smith, Lois E H}
}
@article {1642015,
	title = {A new non-human primate model of desiccating stress-induced dry eye disease},
	journal = {Sci Rep},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 May 13},
	pages = {7957},
	abstract = {Dry eye disease (DED), a multifactorial ocular surface disease, is estimated to affect up to 34\% of individuals over 50\&nbsp;years old. Although numerous animal models, including rodents and rabbits, have been developed to mimic the pathophysiologic mechanisms involved in dry eye, there is a lack of non-human primate (NHP) models, critical for translational drug studies. Here, we developed a novel desiccating stress-induced dry eye disease model using Rhesus macaque monkeys. The monkeys were housed in a controlled environment room for 21 to 36\&nbsp;days under humidity, temperature, and airflow regulation. Following desiccating stress, NHPs demonstrated clinical symptoms similar to those of humans, as shown by increased corneal fluorescein staining (CFS) and decreased tear-film breakup\&nbsp;time (TFBUT). Moreover, corticosteroid treatment significantly reduced CFS scoring, restored TFBUT, and prevented upregulation of tear proinflammatory cytokines as observed in dry eye patients following steroid treatment. The close resemblance of clinical symptoms and treatment responses to those of human DED patients provides great translational value to the NHP model, which could serve as a clinically relevant animal model to study the efficacy of new potential treatments for DED.},
	keywords = {Animals, Dry Eye Syndromes, Fatigue Syndrome, Chronic, Fluorescein, Humans, Macaca mulatta, Rabbits, Tears},
	issn = {2045-2322},
	doi = {10.1038/s41598-022-12009-7},
	author = {Gong, Li and Guan, Yilin and Cho, Wonkyung and Li, Baowen and Pan, Lingzhen and Yang, Zhenyan and Wu, Mingling and Yang, Zunyuan and Chauhan, Sunil K and Zeng, Wen}
}
@article {1559558,
	title = {Golgi α1,2-mannosidase I induces clustering and compartmentalization of CD147 during epithelial cell migration},
	journal = {Cell Adh Migr},
	volume = {14},
	number = {1},
	year = {2020},
	month = {2020 12},
	pages = {96-105},
	abstract = {CD147 is a widely expressed matrix metalloproteinase inducer involved in the regulation of cell migration. The high glycosylation and ability to undergo oligomerization have been linked to CD147 function, yet there is limited understanding on the molecular mechanisms behind these processes. The current study demonstrates that the expression of Golgi α1,2-mannosidase I is key to maintaining the cell surface organization of CD147 during cell migration. Using an in vitro model of stratified human corneal epithelial wound healing, we show that CD147 is clustered within lateral plasma membranes at the leading edge of adjacent migrating cells. This localization correlates with a surge in matrix metalloproteinase activity and an increase in the expression of α1,2-mannosidase subtype IC (MAN1C1). Global inhibition of α1,2-mannosidase I activity with deoxymannojirimycin markedly attenuates the glycosylation of CD147 and disrupts its surface distribution at the leading edge, concomitantly reducing the expression of matrix metalloproteinase-9. Likewise, treatment with deoxymannojirimycin or siRNA-mediated knockdown of MAN1C1 impairs the ability of the carbohydrate-binding protein galectin-3 to stimulate CD147 clustering in unwounded cells. We conclude that the mannose-trimming activity of α1,2-mannosidase I coordinates the clustering and compartmentalization of CD147 that follows an epithelial injury.},
	issn = {1933-6926},
	doi = {10.1080/19336918.2020.1764170},
	author = {Gonzalez-Andrades, Miguel and Jalimarada, Supriya S and Rodriguez-Benavente, Maria and Feeley, Marissa N and Woodward, Ashley M and AbuSamra, Dina B and Arg{\"u}eso, Pablo}
}
@article {630216,
	title = {Establishment of a novel in vitro model of stratified epithelial wound healing with barrier function.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016},
	pages = {19395},
	abstract = {The repair of wounds through collective movement of epithelial cells is a fundamental process in multicellular organisms. In stratified epithelia such as the cornea and skin, healing occurs in three steps that include a latent, migratory, and reconstruction phases. Several simple and inexpensive assays have been developed to study the biology of cell migration in vitro. However, these assays are mostly based on monolayer systems that fail to reproduce the differentiation processes associated to multilayered systems. Here, we describe a straightforward in vitro wound assay to evaluate the healing and restoration of barrier function in stratified human corneal epithelial cells. In this assay, circular punch injuries lead to the collective migration of the epithelium as coherent sheets. The closure of the wound was associated with the restoration of the transcellular barrier and the re-establishment of apical intercellular junctions. Altogether, this new model of wound healing provides an important research tool to study the mechanisms leading to barrier function in stratified epithelia and may facilitate the development of future therapeutic applications.},
	issn = {2045-2322},
	doi = {10.1038/srep19395},
	author = {Gonzalez-Andrades, Miguel and Alonso-Pastor, Luis and Mauris, J{\'e}r{\^o}me and Cruzat, Andrea and Dohlman, Claes H and Arg{\"u}eso, Pablo}
}
@article {1309965,
	title = {Improving the practicality and safety of artificial corneas: Pre-assembly and gamma-rays sterilization of the Boston Keratoprosthesis},
	journal = {Ocul Surf},
	volume = {16},
	number = {3},
	year = {2018},
	month = {2018 Jul},
	pages = {322-330},
	abstract = {PURPOSE: To make the Boston keratoprosthesis (B-KPro), together with its carrier corneal graft, more easily procured, transported and stored, as well as less expensive, easier for the surgeon to implant and safer for the patient, it is proposed that the B-KPro-graft combination be pre-assembled by an expert technician, followed by sterilization with gamma ray irradiation (GI) allowing long-term storage at room temperature. For this to be possible, it must be shown that the B-KPro itself (not only the graft) remains unharmed by the irradiation. METHODS: Polymethyl methacrylate (PMMA) discs and B-KPros were submitted to either ethylene oxide sterilization or different doses of GI. Cell biocompatibility, mechanical strength and optical quality were evaluated. The feasibility of assembling the B-KPro to a corneal graft, and gamma-radiate afterwards, was also assessed. RESULTS: There were no differences in cell biocompatibility between the samples. The optical evaluation showed high levels of transparency for all the groups. The absorbance of ultraviolet was higher for the groups treated with GI. The mechanical evaluation by nanoindentation showed no alterations of the PMMA discs after GI. The flexure test revealed a similar mechanical behavior. Technically, pre-assembly and GI of the B-KPro revealed no problems. CONCLUSIONS: Sterilization of B-KPro using GI has no detrimental influence on the device. The pre-assembly of B-KPro to a donor cornea, followed by gamma sterilization, emerges as an efficient and safe procedure.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.04.002},
	author = {Gonzalez-Andrades, Miguel and Sharifi, Roholah and Islam, Mohammad Mirazul and Divoux, Thibaut and Haist, Michael and Paschalis, Eleftherios I and Gelfand, Larisa and Mamodaly, Shamina and Di Cecilia, Luca and Cruzat, Andrea and Ulm, Franz-Josef and Chodosh, James and Delori, Francois and Dohlman, Claes H}
}
@article {1195266,
	title = {A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment},
	journal = {BMJ Open},
	volume = {7},
	number = {9},
	year = {2017},
	month = {2017 Sep 24},
	pages = {e016487},
	abstract = {INTRODUCTION: There is a need to find alternatives to the use of human donor corneas in transplants because of the limited availability of donor organs, the incidence of graft complications, as well as the inability to successfully perform corneal transplant in patients presenting limbal deficiency, neo-vascularized or thin corneas, etc. We have designed a clinical trial to test a nanostructured fibrin-agarose corneal substitute combining allogeneic cells that mimics the anterior human native cornea in terms of optical, mechanical and biological behaviour. METHODS AND ANALYSIS: This is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in ten Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of this bioengineered human corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed. ETHICS AND DISSEMINATION: The trial protocol received written approval by the corresponding Ethics Committee and the Spanish Regulatory Authority and is currently recruiting subjects. On completion of the trial, manuscripts with the results of phases I and II of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION: CT.gov identifier: NCT01765244 (Jan2013). EudraCT number: 2010-024290-40 (Dec2012).},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2017-016487},
	author = {Gonz{\'a}lez-Andrades, Miguel and Mata, Rosario and Gonz{\'a}lez-Gallardo, Mar{\'\i}a Del Carmen and Medialdea, Santiago and Arias-Santiago, Salvador and Mart{\'\i}nez-Atienza, Juliana and Ruiz-Garc{\'\i}a, Antonio and P{\'e}rez-Fajardo, Lorena and Lizana-Moreno, Antonio and Garz{\'o}n, Ingrid and Campos, Antonio and Alaminos, Miguel and Carmona, Gloria and Cuende, Natividad}
}
@article {1559563,
	title = {Treatment of Experimental Choroidal Neovascularization via RUNX1 Inhibition},
	journal = {Am J Pathol},
	volume = {191},
	number = {3},
	year = {2021},
	month = {2021 03},
	pages = {418-424},
	abstract = {Choroidal neovascularization (CNV) is a prevalent cause of vision loss in patients with age-related macular degeneration. Runt-related transcription factor 1 (RUNX1) has been identified as an important mediator of aberrant retinal angiogenesis in proliferative diabetic retinopathy and its modulation has proven to be effective in curbing pathologic angiogenesis in experimental oxygen-induced retinopathy. However, its role in CNV remains to be elucidated. This study demonstrates RUNX1 expression in critical cell types involved in a laser-induced model of CNV in mice. Furthermore, the preclinical efficacy of Ro5-3335, a small molecule inhibitor of RUNX1, in experimental CNV is reported. RUNX1 inhibitor Ro5-3335, aflibercept-an FDA-approved vascular endothelial growth factor (VEGF) inhibitor, or a combination of both, were administered by intravitreal injection immediately after laser injury. The CNV area of choroidal flatmounts was evaluated by immunostaining with isolectin B4, and vascular permeability was analyzed by fluorescein angiography. A single intravitreal injection of Ro5-3335 significantly decreased the CNV area 7 days after laser injury, and when combined with aflibercept, reduced vascular leakage more effectively than aflibercept alone. These data suggest that RUNX1 inhibition alone or in combination with anti-VEGF drugs may be a new therapy upon further clinical validation for patients with neovascular age-related macular degeneration.},
	keywords = {Angiogenesis Inhibitors, Animals, Choroidal Neovascularization, Core Binding Factor Alpha 2 Subunit, Disease Models, Animal, Female, Male, Mice, Mice, Inbred C57BL, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins, Small Molecule Libraries},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.12.005},
	author = {Gonzalez-Buendia, Lucia and Delgado-Tirado, Santiago and An, Miranda and O{\textquoteright}Hare, Michael and Amarnani, Dhanesh and Whitmore, Hannah A B and Zhao, Guannan and Ruiz-Moreno, Jose M and Arboleda-Velasquez, Joseph F and Kim, Leo A}
}
@article {680411,
	title = {Ophthalmic Surgical Simulation in Training Dexterity in Dominant and Nondominant Hands: Results From a Pilot Study.},
	journal = {J Surg Educ},
	volume = {73},
	number = {4},
	year = {2016},
	month = {2016 Jul-Aug},
	pages = {699-708},
	abstract = {PURPOSE: To determine whether a structured training program using the validated EYESI surgical simulator improves dexterity in nondominant (ND) hands. SETTING: Academic tertiary referral center. DESIGN: Nonrandomized, prospective study. METHODS: Subjects who chose to participate and provided informed consent completed a structured simulation training program, which included a baseline test, 3 sessions of repeated tasks, and a final test on capsulorhexis in dominant (D) and ND hands. Participants completed demographic and satisfaction questionnaires. Performances at each session were recorded. We compared overall scores at baseline and at the end of the study, and analyzed trends over time. Statistical analysis was performed using JMP by SAS. RESULTS: Overall, 14 subjects completed the training program. In all, 3 (21.4\%) were attending physicians and 11 (78.6\%) were trainees. There was a significant improvement in the average overall scores (baseline vs. final) in both the D hand (33.4 vs. 46.5; p \&lt; 0.05) and the ND hand (28.9 vs. 47.7; p \&lt; 0.001). The structured training program demonstrated significantly faster performance times in both hands at the end of the study (D p\&lt; 0.001, ND p \&lt; 0.02). However, the learning curve was significantly steeper in the ND hand (p \&lt; 0.01). Participants agreed that simulation training improved the ND hand dexterity. CONCLUSIONS: We found a significantly greater trend for improvement in the ND compared with the D hand. These results suggest that an elaborate, structured curriculum targeting teaching dexterity results in better simulated performance.},
	issn = {1878-7452},
	doi = {10.1016/j.jsurg.2016.01.014},
	author = {Gonzalez-Gonzalez, Luis A and Payal, Abhishek R and Gonzalez-Monroy, Jose E and Daly, Mary K}
}
@article {1814336,
	title = {Development of a Resveratrol Nanoformulation for the Treatment of Diabetic Retinopathy},
	journal = {Materials (Basel)},
	volume = {17},
	number = {6},
	year = {2024},
	month = {2024 Mar 20},
	abstract = {Diabetic retinopathy (RD) is a microvascular disease that can cause the formation of fragile neovessels, increasing the risk of hemorrhages and leading to vision loss. Current therapies are based on the intravitreal injection of anti-VEGF (vascular endothelial growth factor), which is invasive and can cause secondary effects. The development of new treatments that complement the current therapies is necessary to improve the patient{\textquoteright}s outcomes. Nanostructured formulations offer several advantages regarding drug delivery and penetration. In this research, a resveratrol nanosuspension (RSV-NS) was prepared and characterized using dynamic light scattering, field emission scanning electron microscopy, and infrared spectroscopy. The RSV-NS had an average particle size of 304.0 {\textpm} 81.21 nm with a PDI of 0.225 {\textpm} 0.036, and a spherical-like morphology and uniform particle distribution. Cell viability, proliferation, and migration were tested on endothelial cells (HMRECs). RSV-NS in a concentration of less than 18.75 {\textmu}M did not have a cytotoxic effect on HMRECs. Likewise, proliferation and migration were significantly reduced compared to the unstimulated control at 37.5 {\textmu}M. The RSV-NS did not present cytotoxic effects but decreased cell proliferation and migration, indicating that it could provide an important contribution to future medical implementations and could have a high potential to treat this disease.},
	issn = {1996-1944},
	doi = {10.3390/ma17061420},
	author = {Gonzalez-Perez, Juliana and Lopera-Echavarr{\'\i}a, A M and Arevalo-Alquichire, Said and Araque-Mar{\'\i}n, Pedronel and Londo{\~n}o, Martha E}
}
@article {1354338,
	title = {Dacryops in the setting of a Boston type II keratoprosthesis},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {30},
	number = {3},
	year = {2014},
	month = {2014 May-Jun},
	pages = {e73-5},
	abstract = {Dacryops of the lacrimal tissue can develop under diverse circumstances. Recent evidence suggests that scarring or obstruction of the lacrimal ducts may lead to their dilatation and formation of a cystic structure. Patients who undergo repeated orbital surgery may therefore be at greater risk of dacryops formation. In this report, a patient who underwent multiple corneal and glaucoma procedures including Boston type II keratoprosthesis, after acid burns to both eyes, is described. Over time, a fluid-filled collection developed in the lower orbit. On surgical exploration and incision, fluid was drained from a cystic lesion which abutted the lacrimal gland and spanned the upper and lower orbits. The lesion was removed and was proven by histopathology and immunohistochemistry to be dacryops. This is the first known case of dacryops associated with Boston type II keratoprosthesis.},
	keywords = {Bioartificial Organs, Burns, Chemical, Cornea, Corneal Diseases, Cysts, Drainage, Eye Burns, Humans, Lacrimal Apparatus Diseases, Male, Middle Aged, Prosthesis Implantation, Tomography, X-Ray Computed, Visual Acuity},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31829d0270},
	author = {Gonzalez-Saldivar, Gerardo and Lee, N Grace and Chodosh, James and Freitag, Suzanne K and Stacy, Rebecca C}
}
@article {1664962,
	title = {Cataract surgery in patients with underlying keratoconus: focused review},
	journal = {J Cataract Refract Surg},
	volume = {49},
	number = {1},
	year = {2023},
	month = {2023 Jan 01},
	pages = {97-102},
	abstract = {An underlying diagnosis of keratoconus (KC) can complicate cataract surgery. In this study, the results of a focused review of the literature pertaining to cataract surgery in patients with KC are detailed. Topics essential for the appropriate management of this patient population are discussed. First, the individual and shared epidemiology and pathophysiology of cataract and KC are reviewed. Then, the theory and approach to intraocular lens power calculation are discussed, highlighting particularities and pitfalls of this exercise when performed in patients with KC. Finally, several special-although not uncommon-management scenarios and questions are addressed, such as surgical planning in cases where corneal stabilization or tissue replacement interventions are also necessitated.},
	keywords = {Cataract, Cataract Extraction, Cornea, Corneal Topography, Humans, Keratoconus, Visual Acuity},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000001069},
	author = {Gonzalez-Salinas, Roberto and Franco, Jovany Jeomar and Reyes-Luis, Jos{\'e} Luis and S{\'a}nchez-Huerta, Valeria and de Wit-Carter, Guillermo and Hern{\'a}ndez-Quintela, Everardo and Pineda, Roberto}
}
@article {1635651,
	title = {Safety of Botulinum Toxin A Injections for Facial Rejuvenation: A Meta-Analysis of 9,669 Patients},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {1},
	year = {2023},
	month = {2023 Jan-Feb 01},
	pages = {13-25},
	abstract = {PURPOSE: To quantitatively evaluate safety profile for botulinum toxin A (BTX-A) injections among patients undergoing treatment for cosmetic indications is produced, with special attention to clinically relevant covariates and their relative impact on safety. METHODS: A systematic literature search was performed using PubMed (1996-January 2020) and Embase (1947-January 2020) to identify all randomized controlled trials (RCTs) that reported safety data for patients receiving BTX-A for cosmetic indications compared to placebo. A meta-analysis was performed to determine pooled risk ratios (RR) for treatment-related adverse events (TRAEs) and for specific adverse events. Meta-regression and additional analyses were performed for significant and/or clinically relevant covariates. RESULTS: Following the review of 8,690 studies, 32 RCTs involving 9,669 patients were included. The pooled RR of any TRAE occurring after BTX-A injection compared to placebo injection was 1.53 (95\% CI, 1.33-1.77; p \&lt; 0.001). Statistically significant covariates included individual injection volume and total injection volume. The type of BTX-A formulation, treatment site, total BTX-A units, and BTX-A units per injection were not significant. Specific adverse events more likely to occur following BTX-A injection rather than placebo injection included eyelid/eyebrow malposition (RR 3.55; p \&lt; 0.001), facial paresis (RR 2.42; p = 0.316), and headache (RR 1.45; p = 0.003). Injection site reactions and injection site bruising occurred at similar rates in both groups. CONCLUSIONS: The overall safety profile of BTX-A is acceptable and consistent with previous publications. The authors{\textquoteright} additional analyses provide a relative comparison of the impact of various treatment parameters on safety.},
	keywords = {Botulinum Toxins, Type A, Face, Humans, Injections, Randomized Controlled Trials as Topic, Rejuvenation},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002169},
	author = {Gostimir, Mi{\v s}o and Liou, Victor and Yoon, Michael K}
}
@article {1761806,
	title = {Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia},
	journal = {Biomolecules},
	volume = {13},
	number = {9},
	year = {2023},
	month = {2023 Sep 11},
	abstract = {PURPOSE: We previously reported differential gene expression of the bone morphogenetic protein 2 (Bmp2) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia. METHODS: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular -10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2, Id3, and Nog genes. RESULTS: Mean interocular differences (treated-control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia (p \&lt; 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear (p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day (p = 0.012 and 0.016) and 7 days (p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day (p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation.},
	keywords = {Animals, Antibodies, Bone Morphogenetic Protein 2, Choroid, Guinea Pigs, Myopia, Retinal Pigment Epithelium},
	issn = {2218-273X},
	doi = {10.3390/biom13091373},
	author = {Goto, So and Zhang, Yan and Vyas, Sonal Aswin and Zhu, Qiurong and Wildsoet, Christine F}
}
@article {1638578,
	title = {Ocular abnormalities at diagnosis and after the completion of treatment in children and adolescents with newly diagnosed acute lymphoblastic leukemia},
	journal = {Pediatr Blood Cancer},
	volume = {69},
	number = {4},
	year = {2022},
	month = {2022 Apr},
	pages = {e29542},
	abstract = {BACKGROUND: Ocular abnormalities (OA) in pediatric patients with acute lymphoblastic leukemia (ALL) are common findings both at diagnosis and later in follow-up. The frequency, predictors, and prognostic impact of OA in the context of recent ALL protocols are not well characterized. PROCEDURE: Single-center retrospective analysis of the medical records of 224 patients with ALL enrolled on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05-001. RESULTS: Overall, 217 (98\%) patients had at least one ophthalmic exam. Retinal hemorrhages were the most frequent abnormalities at diagnosis (11\%) and cataracts at later time points (13\%). OA at diagnosis were associated with age >=10\&nbsp;years and with the severity of anemia and thrombocytopenia; they were also univariately associated with lower 5-year event-free survival (EFS) (high risk [HR]\&nbsp;=\&nbsp;3.09 [95\% CI: 1.38-6.94]; p\&nbsp;=\&nbsp;.006), but not in a disease-free survival (DFS) model adjusted for end-induction minimal residual disease (p\&nbsp;=\&nbsp;.82). The cumulative incidence of cataract was 13.1\% {\textpm} 2.8\% at 43\&nbsp;months from diagnosis; its development was associated with high presenting white blood cell count (>=50,000/μl) (p\&nbsp;=\&nbsp;.010), male sex (p\&nbsp;=\&nbsp;.036), higher risk group (p\&nbsp;=\&nbsp;.025), and cranial radiation (p\&nbsp;=\&nbsp;.004). Cataract was associated with decreased visual acuity. CONCLUSIONS: OA at diagnosis, present in 12\% of patients, were associated with older age, anemia, and thrombocytopenia and did not carry a significant prognostic impact. Cataracts were detected in over 10\% of patients and were associated with decreased visual acuity, thus supporting routine screening after completion of therapy, especially for those treated with high-risk protocols.},
	issn = {1545-5017},
	doi = {10.1002/pbc.29542},
	author = {Gotti, Giacomo and Stevenson, Kristen and Kay-Green, Samantha and Blonquist, Traci M and Mantagos, Jason S and Silverman, Lewis B and Place, Andrew E}
}
@article {1645487,
	title = {Reply to: Comment on: Ocular abnormalities at diagnosis and after the completion of treatment in children and adolescents with newly diagnosed acute lymphoblastic leukemia},
	journal = {Pediatr Blood Cancer},
	volume = {70},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {e29833},
	keywords = {Adolescent, Asparaginase, Child, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma},
	issn = {1545-5017},
	doi = {10.1002/pbc.29833},
	author = {Gotti, Giacomo and Stevenson, Kristen and Kay-Green, Samantha and Blonquist, Traci M and Mantagos, Jason S and Silverman, Lewis B and Place, Andrew E}
}
@article {1043231,
	title = {Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability},
	journal = {Biomaterials},
	volume = {121},
	year = {2017},
	month = {2017 Mar},
	pages = {205-219},
	abstract = {Ideally, biomaterials designed to play specific physical and physiological roles in\&nbsp;vivo should comprise components and microarchitectures analogous to those of the native tissues they intend to replace. For that, implantable biomaterials need to be carefully designed to have the correct structural and compositional properties, which consequently impart their bio-function. In this study, we showed that the control of such properties can be defined from the bottom-up, using smart surface templates to modulate the structure, composition, and bio-mechanics of human transplantable tissues. Using multi-functional peptide amphiphile-coated surfaces with different anisotropies, we were able to control the phenotype of corneal stromal cells and instruct them to fabricate self-lifting tissues that closely emulated the native stromal lamellae of the human cornea. The type and arrangement of the extracellular matrix comprising these corneal stromal Self-Lifting Analogous Tissue Equivalents (SLATEs) were then evaluated in detail, and was shown to correlate with tissue function. Specifically, SLATEs comprising aligned collagen fibrils were shown to be significantly thicker, denser, and more resistant to proteolytic degradation compared to SLATEs formed with randomly-oriented constituents. In addition, SLATEs were highly transparent while providing increased absorption to near-UV radiation. Importantly, corneal stromal SLATEs were capable of constituting tissues with a higher-order complexity, either by creating thicker tissues through stacking or by serving as substrate to support a fully-differentiated, stratified corneal epithelium. SLATEs were also deemed safe as implants in a rabbit corneal model, being capable of integrating with the surrounding host tissue without provoking inflammation, neo-vascularization, or any other signs of rejection after a 9-months follow-up. This work thus paves the way for the de novo bio-fabrication of easy-retrievable, scaffold-free human tissues with controlled structural, compositional, and functional properties to replace corneal, as well as other, tissues.},
	issn = {1878-5905},
	doi = {10.1016/j.biomaterials.2016.12.023},
	author = {Gouveia, Ricardo M and Gonz{\'a}lez-Andrades, Elena and Cardona, Juan C and Gonz{\'a}lez-Gallardo, Carmen and Ionescu, Ana M and Garzon, Ingrid and Alaminos, Miguel and Gonz{\'a}lez-Andrades, Miguel and Connon, Che J}
}
@article {1608592,
	title = {Association between post-concussion symptoms and oculomotor deficits among adolescents},
	journal = {Brain Inj},
	year = {2021},
	month = {2021 Aug 12},
	pages = {1-11},
	abstract = {PURPOSE: To examine the association between Post-Concussion Symptom Scale (PCSS) scores, Convergence Insufficiency Symptom Survey (CISS) scores, and oculomotor deficits post-concussion. METHODS: Records of adolescent patients examined in a multidisciplinary concussion clinic between July 2014 and May 2019 were reviewed. PCSS\&nbsp;and CISS scores, results of eye examination and oculomotor assessment, concussion history, and demographics were abstracted. RESULTS: One hundred and forty patient records (median age, 15.3\&nbsp;years; 52 males, presented 109\&nbsp;days (median) from their most recent concussion) met inclusion criteria. Mean total scores on PCSS and CISS were 46.67\&nbsp;{\textpm}\&nbsp;25.89 and 27.13\&nbsp;{\textpm}\&nbsp;13.22, respectively, and were moderately correlated with each other (r\&nbsp;=\&nbsp;0.53, p \&lt;\&nbsp;.001). Oculomotor deficits were observed in 123 (88\%) patients. Step-wise linear regression identified increased PCSS total score to be significantly associated with decreased amplitude of accommodation (p \&lt;\&nbsp;.001). Increased CISS total score was significantly associated with receded near point of convergence, developmental eye movement test error scores, and cause of concussion. CONCLUSION: High PCSS scores may indicate an accommodation deficit and thus prompt an oculomotor assessment in patients following a concussion. Using the CISS and a detailed oculomotor assessment may reveal underlying oculomotor deficits, which may benefit from treatment.},
	issn = {1362-301X},
	doi = {10.1080/02699052.2021.1959065},
	author = {Gowrisankaran, Sowjanya and Shah, Ankoor S and Roberts, Tawna L and Wiecek, Emily and Chinn, Ryan N and Hawash, Karameh K and O{\textquoteright}Brien, Michael J and Howell, David R and Meehan, William P and Raghuram, Aparna}
}
@article {1629467,
	title = {Mouse Lines with Cre-Mediated Recombination in Retinal Amacrine Cells},
	journal = {eNeuro},
	volume = {9},
	number = {1},
	year = {2022},
	month = {2022 Jan-Feb},
	abstract = {Amacrine cells (ACs) are the most diverse neuronal cell type in the vertebrate retina. Yet little is known about the contribution of ACs to visual processing and retinal disease. A major challenge in evaluating AC function is genetic accessibility. A classic tool of mouse genetics, Cre-mediated recombination, can provide such access. We have screened existing genetically-modified mouse strains and identified multiple candidates that express Cre-recombinase in subsets of retinal ACs. The Cre-expressing mice were crossed to fluorescent-reporter mice to assay Cre expression. In addition, a Cre-dependent fluorescent reporter plasmid was electroporated into the subretinal space of Cre strains. Herein, we report three mouse lines (Tac1::IRES-cre, Camk2a-cre, and Scx-cre) that express Cre recombinase in sub-populations of ACs. In two of these lines, recombination occurred in multiple AC types and a small number of other retinal cell types, while recombination in the Camk2a-cre line appears specific to a morphologically distinct AC. We anticipate that these characterized mouse lines will be valuable tools to the community of researchers who study retinal biology and disease.},
	issn = {2373-2822},
	doi = {10.1523/ENEURO.0255-21.2021},
	author = {G{\"o}z Ayt{\"u}rk, Didem and You, Wenjia and Cepko, Constance L}
}
@article {987956,
	title = {Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism},
	journal = {Doc Ophthalmol},
	volume = {134},
	number = {2},
	year = {2017},
	month = {2017 Apr},
	pages = {135-140},
	abstract = {PURPOSE: We report for the first time electroretinographic (ERG) evidence of progressive retinal abnormalities in a girl who presented in infancy with ocular features of albinism and gradually developed choroidal sclerosis and patchy retinal atrophy leading to a diagnosis of Knobloch syndrome (KS, OMIM 267750, COL18A1). METHODS: At age 2\&nbsp;months, nystagmus and esotropia prompted ophthalmic evaluation. The appearance of choroidal sclerosis and atrophic retinal patches led to further evaluation at age 8\&nbsp;years. Genetics consultation was obtained in infancy and again at age 8\&nbsp;years as retinal findings evolved.\&nbsp;Full field ERG responses in both scotopic and photopic conditions were recorded at both ages and compared to those in healthy control subjects. RESULTS: At age 2\&nbsp;months ERG response parameters were within normal limits for age and tyrosinase (TYR) gene sequencing revealed one novel mutation, p.S466F, and the temperature-sensitive polymorphism, p.R402Q, suggesting the diagnosis of oculocutaneous albinism type 1 (OCA1). At age 8\&nbsp;years, there was significant attenuation of both scotopic and photopic ERG responses. Genetic re-analysis led to the identification of a homozygous mutation, c.3213dupC, in the COL18A1 gene, thus confirming the diagnosis of Knobloch syndrome. CONCLUSIONS: Our patient with Knobloch syndrome developed abnormal ERG responses similar to those found in col18a1 knockout mice. Thus, we have documented progressive attenuation of the scotopic and photopic responses in KS.},
	issn = {1573-2622},
	doi = {10.1007/s10633-017-9574-1},
	author = {Gradstein, Libe and Hansen, Ronald M and Cox, Gerald F and Altschwager, Pablo and Fulton, Anne B}
}
@article {541296,
	title = {Changes in Lateral Comitance After Asymmetric Horizontal Strabismus Surgery.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {11},
	year = {2015},
	month = {2015 Nov 1},
	pages = {1241-6},
	abstract = {IMPORTANCE: Asymmetric horizontal strabismus surgery is often performed to correct primary gaze alignment without considering the symptoms that may result from misalignment in the patient{\textquoteright}s side gaze. Surgical choices influence alignment in side gaze and may contribute to functional and social deficits. OBJECTIVE: To identify the surgical procedures associated with changes of alignment in side gaze to help inform surgical planning for patients with horizontal strabismus. DESIGN, SETTING, AND PARTICIPANTS: The medical records of 1081 horizontal strabismus surgical procedures that were performed at Boston Children{\textquoteright}s Hospital during a 2-year period were retrospectively reviewed. Only records with strabismus measurements recorded in the right and left gaze before and after surgery were included. Data analysis was conducted from September 1, 2012, through June 7, 2015. MAIN OUTCOMES AND MEASURES: Change in comitance (CIC), determined by measuring the horizontal comitance (the difference between right- and left-gaze strabismus measurements) before and after surgery. RESULTS: The review identified 569 patients who met the inclusion criteria. Of the 491 patients with comitant preoperative alignment, 59 developed postoperative incomitance, of whom 53 (89.9\%) had asymmetric surgery. Of the 78 patients with incomitant preoperative alignment, 36 patients{\textquoteright} (46.2\%) deviation had improved to comitance after surgery; 32 (88.9\%) of these patients had asymmetric surgery. Asymmetric 2-muscle surgery had a median CIC of 4.0 while symmetric 2-muscle surgery had a median CIC of 1.5 (difference in CIC, 2.5; 95\% CI, 2.0-3.0; P \&lt; .001). A CIC of 25 prism diopters or more was observed in 6 patients who underwent asymmetric surgery (0 with symmetric surgery). New postoperative incomitance was symptomatic in at least 17 patients (28.8\%). CONCLUSIONS AND RELEVANCE: Asymmetric strabismus surgery can treat incomitant deviations, but it can also create symptomatic incomitant deviations in patients who were previously comitant. Surgical planning should include consideration of the potential for CIC, including the potential for unsatisfactory appearance in side gaze. Patients with binocular vision will be sensitive to diplopia in any gaze direction; in such cases, the consequences of asymmetric surgery should be considered with particular care.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.2721},
	author = {Graeber, Carolyn P and Hunter, David G}
}
@article {1603872,
	title = {Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3},
	journal = {Dev Neurosci},
	year = {2021},
	month = {2021 Jul 02},
	pages = {1-15},
	abstract = {Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.},
	issn = {1421-9859},
	doi = {10.1159/000516665},
	author = {Gram, Magnus and Ekstr{\"o}m, Claes and Holmqvist, Bo and Carey, Galen and Wang, Xiaoyang and Vallius, Suvi and Hellstr{\"o}m, William and Ortenl{\"o}f, Niklas and Agyemang, Alex Adusei and Smith, Lois E H and Hellstr{\"o}m, Ann and Mangili, Alexandra and Barton, Norman and Ley, David}
}
@article {1347436,
	title = {Altered White Matter Organization in the TUBB3 E410K Syndrome},
	journal = {Cereb Cortex},
	year = {2018},
	month = {2018 Oct 01},
	abstract = {Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G\&gt;A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain{\textquoteright}s structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.},
	issn = {1460-2199},
	doi = {10.1093/cercor/bhy231},
	author = {Grant, P Ellen and Im, Kiho and Ahtam, Banu and Laurentys, Cynthia T and Chan, Wai-Man and Brainard, Maya and Chew, Sheena and Drottar, Marie and Robson, Caroline D and Drmic, Irene and Engle, Elizabeth C}
}
@article {341641,
	title = {Idiopathic vitritis in the setting of Boston keratoprosthesis.},
	journal = {Cornea},
	volume = {34},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {165-70},
	abstract = {PURPOSE: The aim of this study was to revisit the clinical paradigm attributed to Boston keratoprosthesis recipients presenting with idiopathic vitreous inflammation. METHODS: A retrospective chart review was performed of keratoprosthesis recipients at Massachusetts Eye and Ear Infirmary, from January 2000 to August 2013, for demographic data, indication(s) for surgery, timing and presentation of vitreous inflammation, and best-corrected visual acuity at baseline, on presentation, and after resolution of vitritis. RESULTS: Twenty-three (23 eyes) of 346 patients developed idiopathic vitreous inflammation after keratoprosthesis implantation. Six of 23 patients presented with signs and symptoms similar to infectious endophthalmitis but were culture negative. The proportion of patients who fit the previous paradigm of sudden painless loss of vision without external signs of infection ("sterile vitritis") at their first presentation with vitritis was only 4 of 23. Vision decline was variable (median, 9 lines on Snellen chart; range, 0-24), as was time to recovery of best vision (median, 8.9 weeks; range, 0.9-36.7). Nine eyes had repeat bouts (43 episodes in 23 patients). Ten of 43 episodes did not recover to baseline vision. Seventeen of 23 eyes with idiopathic vitritis after keratoprosthesis later developed other complications. CONCLUSIONS: The current paradigm for idiopathic vitritis after keratoprosthesis implantation includes sudden painless loss of vision with full recovery of vision on treatment with periocular corticosteroids. However, idiopathic vitritis after keratoprosthesis can also mimic infectious endophthalmitis with pain and external signs of inflammation. Visual loss can be gradual. Vision may not recover to baseline despite treatment. Vitritis may be a part of a common pathway of chronic inflammation after keratoprosthesis.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000328},
	author = {Grassi, Christina M and Crnej, Alja and Paschalis, Eleftherios I and Colby, Kathryn A and Dohlman, Claes H and Chodosh, James}
}
@article {503926,
	title = {Periprosthetic Tissue Loss in Patients With Idiopathic Vitreous Inflammation After the Boston Keratoprosthesis.},
	journal = {Cornea},
	volume = {34},
	number = {11},
	year = {2015},
	month = {2015 Nov},
	pages = {1378-82},
	abstract = {PURPOSE: Idiopathic vitritis is a poorly understood complication after Boston keratoprosthesis surgery with unclear etiology. We sought to determine whether an association exists between periprosthetic corneal tissue loss and the development of idiopathic vitritis in keratoprosthesis recipients. METHODS: Thirteen Boston type I keratoprosthesis recipient eyes with a history of idiopathic vitritis and 34 type I keratoprosthesis recipient eyes with no history of idiopathic vitritis underwent anterior segment optical coherence tomography (AS-OCT) at a median time postoperatively of 2.4 years versus 1.9 years (range, 0.5-14.2 vs. 0.1-13.6 years), respectively. Areas of corneal graft tissue loss ("gaps") around the keratoprosthesis stem were identified and analyzed by 2 masked observers. The difference in the presence, number, and size of gaps was compared between cases and controls. RESULTS: A periprosthetic gap was identified more commonly in idiopathic vitritis cases than in controls on AS-OCT (11/13, 86\% vs. 11/34, 33.3\%, P \&lt; 0.001). The number of gaps between cases and controls was also significantly different (2.6 {\textpm} 1.6 vs. 0.5 {\textpm} 0.8, P \&lt; 0.001), but not the estimated gap area (0.056 {\textpm} 0.049 mm vs. 0.039 {\textpm} 0.025 mm, P = 0.22). CONCLUSIONS: A significantly higher proportion of keratoprosthesis recipient eyes with idiopathic vitritis had corneal tissue loss around the keratoprosthesis stem than did controls. Tissue loss could serve as an entry point for debris or bacterial components, triggering idiopathic vitritis. Our study underscores the utility of AS-OCT imaging in the postoperative management of keratoprosthesis patients.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000557},
	author = {Grassi, Christina M and Cruzat, Andrea and Taniguchi, Elise V and Crnej, Alja and Colby, Kathryn A and Dohlman, Claes H and Chodosh, James}
}
@article {1598060,
	title = {Adult-onset asthma and periocular xanthogranuloma - A rare infiltrative disease of the orbit and eyelid},
	journal = {Am J Ophthalmol Case Rep},
	volume = {22},
	year = {2021},
	month = {2021 Jun},
	pages = {101043},
	abstract = {Purpose: To present a case of adult onset asthma with periocular xanthogranuloma (AAPOX), and discuss existing literature on adult orbital xanthogranulomatous diseases (AOXGDs) and their treatment. Observations: A 63 year old male presented with progressive bilateral eyelid swelling with overlying yellow plaques associated with asthma. CT scan showed periorbital swelling with enlargement of the superior and lateral rectus muscles bilaterally. Biopsy demonstrated orbital xanthogranulomatous disease with increased IgG4 plasma cells. The patient was treated with intralesional triamcinolone, oral prednisone, and cyclophosphamide without significant improvement. Surgical debulking was eventually performed which improved his external symptoms until he was lost to follow up 15 months later. Conclusions and Importance: AOXGDs are a group of rare infiltrative diseases of the eyelids and orbit that can be associated with significant systemic morbidities. While they all have similar underlying histopathologic features, appreciating the clinical difference between these diseases is important in understanding patient prognosis and ensuring appropriate clinical monitoring. There is also growing research demonstrating that AAPOX, along with other AOXGDs, may represent part of a continuum of IgG4 related disease, similar to what is seen in this case. There is currently no reliably effective treatment for AOXGDs, and additional research into the management of these diseases is necessary.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2021.101043},
	author = {Green, Michael B and Daly, Mary K and Laver, Nora M V and Lefebvre, Daniel R}
}
@article {836846,
	title = {Mouse Models of NMNAT1-Leber Congenital Amaurosis (LCA9) Recapitulate Key Features of the Human Disease.},
	journal = {Am J Pathol},
	volume = {186},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {1925-38},
	abstract = {The nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) enzyme is essential for regenerating the nuclear pool of NAD(+) in all nucleated cells in the body, and mounting evidence also suggests that it has a separate role in neuroprotection. Recently, mutations in the NMNAT1 gene were associated with Leber congenital amaurosis, a severe retinal degenerative disease that causes blindness during infancy. Availability of a reliable mammalian model of NMNAT1-Leber congenital amaurosis would assist in determining the mechanisms through which disruptions in NMNAT1 lead to retinal cell degeneration and would provide a resource for testing treatment options. To this end, we identified two separate N-ethyl-N-nitrosourea-generated mouse lines that harbor either a p.V9M or a p.D243G mutation. Both mouse models recapitulate key aspects of the human disease and confirm the pathogenicity of mutant NMNAT1. Homozygous Nmnat1 mutant mice develop a rapidly progressing chorioretinal disease that begins with photoreceptor degeneration and includes attenuation of the retinal vasculature, optic atrophy, and retinal pigment epithelium loss. Retinal function deteriorates in both mouse lines, and, in the more rapidly progressing homozygous Nmnat1(V9M) mutant mice, the electroretinogram becomes undetectable and the pupillary light response weakens. These mouse models offer an opportunity for investigating the cellular mechanisms underlying disease pathogenesis, evaluating potential therapies for NMNAT1-Leber congenital amaurosis, and conducting in situ studies on NMNAT1 function and NAD(+) metabolism.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2016.03.013},
	author = {Greenwald, Scott H and Charette, Jeremy R and Staniszewska, Magdalena and Shi, Lan Ying and Brown, Steve D M and Stone, Lisa and Liu, Qin and Hicks, Wanda L and Collin, Gayle B and Bowl, Michael R and Krebs, Mark P and Nishina, Patsy M and Pierce, Eric A}
}
@article {1586192,
	title = {Mutant Nmnat1 leads to a retina-specific decrease of NAD+ accompanied by increased poly(ADP-ribose) in a mouse model of NMNAT1-associated retinal degeneration},
	journal = {Hum Mol Genet},
	volume = {30},
	number = {8},
	year = {2021},
	month = {2021 May 17},
	pages = {644-657},
	abstract = {Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is required for nuclear nicotinamide adenine mononucleotide (NAD+) biosynthesis in all nucleated cells, and despite its functional ubiquity, mutations in this gene lead to an isolated retinal degeneration. The mechanisms underlying how mutant NMNAT1 causes disease are not well understood, nor is the reason why the pathology is confined to the retina. Using a mouse model of NMNAT1-associated retinal degeneration that harbors the p.Val9Met mutation, we tested the hypothesis that decreased function of mutant NMNAT1 has a greater effect on the levels of NAD+ in the retina than elsewhere in the body. Measurements by liquid chromatography with tandem mass spectrometry showed an early and sustained decrease of NAD+ in mutant retinas that was not observed in other tissues. To understand how consumers of nuclear NAD+ are affected by the reduced availability of NAD+ in mutant retinas, poly(ADP-ribose) polymerase (PARP) and nuclear sirtuin activity were evaluated. PARP activity was elevated during disease progression, as evidenced by overproduction of poly(ADP-ribose) (PAR) in photoreceptors, whereas histone deacetylation activity of nuclear sirtuins was not altered. We hypothesized that PARP could be activated because of elevated levels of oxidative stress; however, we did not observe oxidative DNA damage, lipid peroxidation, or a low glutathione to oxidized glutathione ratio. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining revealed that photoreceptors appear to ultimately die by apoptosis, although the low NAD+ levels and overproduction of PAR suggest that cell death may include aspects of the parthanatos cell death pathway.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddab070},
	author = {Greenwald, Scott H and Brown, Emily E and Scandura, Michael J and Hennessey, Erin and Farmer, Raymond and Du, Jianhai and Wang, Yekai and Pierce, Eric A}
}
@article {1347437,
	title = {Soluble Fas ligand blocks destructive corneal inflammation in mouse models of corneal epithelial debridement and LPS induced keratitis},
	journal = {Exp Eye Res},
	volume = {179},
	year = {2019},
	month = {2019 Feb},
	pages = {47-54},
	abstract = {Neutrophil-mediated inflammation plays a critical role in corneal damage following injury or infection. Previous studies demonstrated that membrane-bound FasL (mFasL) induces neutrophil chemokine production. However, the extracellular domain of mFasL is normally cleaved by matrix metalloproteinases to release a soluble form of FasL (sFasL) and sFasL antagonizes mFasL-mediated chemokine production. Therefore, we hypothesized that sFasL could be used to prevent neutrophil-mediated corneal inflammation associated with injury and bacterial keratitis. To test this hypothesis, GFP-only, sFasL-GFP, or mFasL-GFP were expressed in the corneal stroma of C57BL/6 mice, using intra-stromal injections of plasmid DNA or adenoviral vectors (AV) and the role of mFasL and sFasL in corneal inflammation was examined in models of corneal injury and LPS-induced keratitis. Our work addresses an important area of disagreement in the field of FasL, with regard to the mechanism by which sFasL regulates ocular inflammation. Herein, we demonstrate that an intrastromal injection of GFP-only, sFasL-GFP, or mFasL-GFP plasmid DNA resulted in GFP expression throughout the corneal stroma for up to two weeks with little to no evidence of inflammation in the GFP-only and sFasL-GFP groups and mild corneal inflammation in the mFasL-GFP group. Similarly, following epithelial debridement, corneas expressing GFP-only or sFasL-GFP showed no significant signs of corneal inflammation, with clear corneas at 15 days post debridement. By contrast, epithelial debridement of corneas expressing mFasL-GFP triggered persistent corneal inflammation and the development of central corneal opacities that was blocked by sFasL. Similar to the mFasL-GFP plasmid DNA, intrastromal injection of mFasL-GFP AV triggered mild corneal inflammation, but it was transient and resolved by day 10 with corneas remaining clear out to 30 days post injection. Nevertheless, intrastromal expression of mFasL-GFP AV exacerbated LPS-induced keratitis, corneal opacity, and neovascularization, while sFasL-GFP AV expression prevented LPS-induced keratitis, resulting in a clear cornea. Histological analysis of corneas with LPS-induced keratitis revealed a robust infiltration of macrophages and neutrophils and sFasL expression specifically blocked the neutrophil influx. Overall, our data demonstrate that stromal expression of mFasL is inflammatory, while sFasL is non-inflammatory, and opposes the effects of mFasL in mouse models of epithelial debridement and LPS-induced keratitis. These data demonstrate that a delicate balance between sFasL and mFasL regulates ocular inflammation. This study further identifies sFasL as a potent inhibitor of neutrophil-mediated corneal damage, and supports the potential use of sFasL in the treatment of neutrophil-mediated keratitis. These results strongly support the hypothesis that, in the immune privileged environment of the eye, the isoform of FasL regulates immune privilege and determines the extent of inflammation: mFasL promotes inflammation and sFasL blocks inflammation.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.10.013},
	author = {Gregory-Ksander, Meredith and Perez, Victor L and Marshak-Rothstein, Ann and Ksander, Bruce R}
}
@article {1483598,
	title = {Corneal absorption of glycerylphosphorylcholine},
	journal = {Exp Eye Res},
	volume = {192},
	year = {2020},
	month = {2020 Mar},
	pages = {107932},
	abstract = {This study documents the absorption of glycerylphosphorylcholine (GPC) into corneas ex vivo. Corneas in quadruplicate were incubated in preservation medium containing 30\&nbsp;mM GPC, which is used as a reference marker. The GPC reference marker is used to calibrate P nuclear magnetic resonance (NMR) spectral chemical-shift positions for identification of phosphatic metabolites and to calculate intracorneal pH in intact tissues ex vivo. Following baseline NMR ex vivo analysis, corneas were stored in eye bank chambers in preservation medium containing 30\&nbsp;mM GPC at 4\&nbsp;{\textdegree}C overnight for 8\&nbsp;h. After returning to room temperature, NMR analysis was repeated on the same corneas in fresh GPC-free preservation medium. NMR analysis also was performed on the 30\&nbsp;mM GPC preservation medium alone from the eye bank chambers for detection of the GPC signal. The elevated GPC signal unexpectedly persisted in corneas incubated at 4\&nbsp;{\textdegree}C overnight even though GPC was not present in the fresh GPC-free preservation medium. In fact, the concentration of GPC in the intact cornea was many times higher than that found in the cornea endogenously. The levels of phosphatic metabolites and the energy modulus, after subtracting the spectral contribution of the 30\&nbsp;mM exogenous GPC, as well as the intracorneal pH remained unchanged from pre-refrigeration analyses. Corneas also retained transparency through the time-course of this study irrespective of temperature or change in temperature. The GPC signal in the NMR analysis of the preservation medium from the eye bank chambers was nearly undetectable. GPC was unexpectedly absorbed into the corneal tissue without detectable metabolic or physical toxicity. The intracorneal uptake of GPC at reduced temperatures parallels the increase in GPC that occurs naturally in muscle tissue in animals during wintering periods and the very high concentration of GPC in sperm, a cryogenically compatible cell, suggestive of a potential role for GPC in cryopreservation.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.107932},
	author = {Greiner, Jack V and Glonek, Thomas and Korb, Donald R and Lindsay, Michael E and Oliver, Paula J}
}
@article {1623361,
	title = {Intracellular ATP Concentration and Implication for Cellular Evolution},
	journal = {Biology (Basel)},
	volume = {10},
	number = {11},
	year = {2021},
	month = {2021 Nov 12},
	abstract = {Crystalline lens and striated muscle exist at opposite ends of the metabolic spectrum. Lens is a metabolically quiescent tissue, whereas striated muscle is a mechanically dynamic tissue with high-energy requirements, yet both tissues contain millimolar levels of ATP (\&gt;2.3 mM), far exceeding their underlying metabolic needs. We explored intracellular concentrations of ATP across multiple cells, tissues, species, and domains to provide context for interpreting lens/striated muscle data. Our database revealed that high intracellular ATP concentrations are ubiquitous across diverse life forms including species existing from the Precambrian Era, suggesting an ancient highly conserved role for ATP, independent of its widely accepted view as primarily "metabolic currency". Our findings reinforce suggestions that the primordial function of ATP was non-metabolic in nature, serving instead to prevent protein aggregation.},
	issn = {2079-7737},
	doi = {10.3390/biology10111166},
	author = {Greiner, Jack V and Glonek, Thomas}
}
@article {1483618,
	title = {Hydrotropic function of ATP in the crystalline lens},
	journal = {Exp Eye Res},
	volume = {190},
	year = {2020},
	month = {2020 Jan},
	pages = {107862},
	abstract = {The hypothesis proposed herein is presented to explain the unexpectedly high concentration of ATP and provide evidence to support its hydrotropic function in the crystalline lens determined using P NMR. The lens, historically considered to be a metabolically quiescent organ, has the requisite machinery to synthesize ATP, such that the homeostatic level is maintained at about 3 mM. This relatively high concentration of ATP has been found to be consistent among multiple mammalian species including humans. This millimolar quantity is many times greater than the micromolar amounts required for the other known functions of ATP. The recent postulation that ATP at millimolar concentrations functions as a hydrotrope in various cell/tissue homogenates preventing protein aggregation coupled with observations presented herein, provide support for extending the hypothesis that ATP functions as a hydrotrope not only in homogenates but in an intact functioning organ, the crystalline lens. Concentrations of ATP of this magnitude are hypothesized to be required to maintain protein solubility and effectively prevent protein aggregation. This concept is important considering protein aggregation is the etiology for age-related cataractogenesis. ATP is a common ubiquitous intracellular molecule possessing the requisite hydrotropic properties for maintaining intracellular proteins in a fluid, non-aggregated state. It is proposed that the amphiphilic ATP molecule shields the hydrophobic regions on intralenticular fiber cell protein molecules and provides a hydrophilic interfacial surface comprised of the ATP negatively charged triphosphate side chain. Evidence is presented that this side chain is exposed to and has been reported to organize intracellular interstitial water to form an interfacial rheologically dynamic water layer. Such organization of water is substantiated with the effect of deuterium oxide (heavy water) on ATP line widths of the side chain phosphates measured ex vivo by P NMR. A novel model is presented to propose how this water layer separates adjacent lens fiber cell proteins, keeping them from aggregating. This hypothesis proposes that ATP can prevent protein aggregation in normal intact lenses, and with declining concentrations can be related to the disease process in age-related cataractogenesis, an affliction that affects every older human being.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.107862},
	author = {Greiner, Jack V and Glonek, Thomas}
}
@article {1363114,
	title = {Long-term (12-month) improvement in meibomian gland function and reduced dry eye symptoms with a single thermal pulsation treatment},
	journal = {Clin Exp Ophthalmol},
	volume = {41},
	number = {6},
	year = {2013},
	month = {2013 Aug},
	pages = {524-30},
	abstract = {PURPOSE: To determine the 1-year post-treatment dry eye status of subjects with meibomian gland dysfunction and dry eye symptoms after receiving a single LipiFlow Thermal Pulsation System treatment. DESIGN: Single-centre, prospective, observational, open-label, 1-month-registered clinical trial with a 1-year follow-up examination. PARTICIPANTS: Patients with evaporative dry eye disease with meibomian gland dysfunction and dry eye symptoms who had participated in the registered 1-month clinical trial. METHODS: Eighteen of 30 subjects initially enrolled were able to return for a 1-year follow-up. Both eyes of all patients were treated with a single 12-min treatment using the LipiFlow Thermal Pulsation System. Meibomian gland function, tear break-up time and dry eye symptoms were measured. Data are presented for pretreatment (baseline), and 1-month and 1-year post-treatment. MAIN OUTCOME MEASURES: Meibomian gland secretion scores, and tear break-up time and dry eye symptoms. RESULTS: Significant improvement in meibomian gland secretion scores from baseline measurements (4.0 {\textpm} 3.4) to 1-month post-treatment (11.3 {\textpm} 4.7; P \&lt; 0.0005) was maintained at 1-year (7.3 {\textpm} 4.6; P \&lt; 0.05). Baseline tear break-up time (4.9 {\textpm} 3.0) was significantly increased at 1-month (9.5 {\textpm} 6.9; P \&lt; 0.05); however, this improvement was no longer evident at 1-year post-treatment (6.0 {\textpm} 4.4). The significant improvement in symptom scores on Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires observed at 1-month (P \&lt; 0.0005) was maintained at 1-year (Ocular Surface Disease Index [P \&lt; 0.05]; Standard Patient Evaluation of Eye Dryness [P \&lt; 0.0005]). CONCLUSION: A single 12-min treatment with the Lipi Flow Thermal Pulsation System offers an effective treatment for evaporative dry eye and meibomian gland dysfunction resulting in significant and sustained improvement in signs and symptoms for up to 1 year.},
	keywords = {Dry Eye Syndromes, Eyelid Diseases, Female, Humans, Hyperthermia, Induced, Male, Meibomian Glands, Middle Aged, Prospective Studies, Surveys and Questionnaires, Tears, Treatment Outcome},
	issn = {1442-9071},
	doi = {10.1111/ceo.12033},
	author = {Greiner, Jack V}
}
@article {1664971,
	title = {Association of Tear Osmolarity With Signs and Symptoms of Dry Eye Disease in the Dry Eye Assessment and Management (DREAM) Study},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {1},
	year = {2023},
	month = {2023 Jan 03},
	pages = {5},
	abstract = {PURPOSE: To determine the relationships of (1) tear osmolarity (TO) levels with the severity of signs and symptoms of dry eye disease (DED) and (2) changes in TO with changes in signs and symptoms. METHODS: Patients (N = 405) with moderate to severe DED in the Dry Eye Assessment and Management (DREAM) Study were evaluated at baseline and at six and 12 months. Associations of TO with signs and symptoms were evaluated using Pearson correlation coefficient (r) and regression models. RESULTS: The mean (standard deviation [SD]) TO was 303 (16) mOsm/L at baseline and 303 (18) mOsm/L at both six and 12 months. TO was higher in older patients (306 mOsm/L for >=70 years vs. 300 mOsm/L for \&lt;50 years; P = 0.01) and those with Sj{\"o}gren{\textquoteright}s disease (311 vs. 302 mOsm/L; P \&lt; 0.0001). TO did not differ between patients randomized to placebo and omega-3 fatty acid supplementation. TO was weakly correlated with conjunctival (r = 0.18; P \&lt; 0.001) and corneal staining scores (r = 0.17; P \&lt; 0.001), tear film break-up time (r = 0.06; P = 0.03), and Schirmer test score (r = -0.07; P = 0.02) but not with Ocular Surface Disease Index scores (r = 0.03; P = 0.40). Changes in signs and were not significantly correlated with change in TO at six or 12 months. CONCLUSIONS: Within DREAM, TO was weakly correlated with DED signs, explaining \&lt;5\% variability in signs. Changes in tear osmolarity were not associated with changes in signs and symptoms of DED, indicating that the association may not be causal.},
	keywords = {Aged, Conjunctiva, Dry Eye Syndromes, Humans, Osmolar Concentration, Sjogren{\textquoteright}s Syndrome, Tears},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.1.5},
	author = {Greiner, Jack V and Ying, Gui-Shuang and Pistilli, Maxwell and Maguire, Maureen G and Asbell, Penny A and Dry Eye Assessment and Management (DREAM) Study Research Group}
}
@article {1364608,
	title = {A single LipiFlow{\textregistered} Thermal Pulsation System treatment improves meibomian gland function and reduces dry eye symptoms for 9 months},
	journal = {Curr Eye Res},
	volume = {37},
	number = {4},
	year = {2012},
	month = {2012 Apr},
	pages = {272-8},
	abstract = {PURPOSE: To evaluate the effect of a single treatment with the LipiFlow({\textregistered}) Thermal Pulsation System on signs of meibomian gland dysfunction (MGD) and dry eye symptoms over a 9-month period. METHODS: Patients (n = 42 eyes, 21 subjects) diagnosed with MGD and dry eye symptoms were recruited for a non-significant risk, prospective, open-label, 1-month clinical trial. Patients received a single 12-minute treatment using the LipiFlow({\textregistered}) Thermal Pulsation System on each eye. The LipiFlow({\textregistered}) device applies heat to the conjunctival surfaces of the upper and lower inner eyelids while simultaneously applying pulsatile pressure to the outer eyelid surfaces to express the meibomian glands. Patient symptoms were evaluated using the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation for Eye Dryness (SPEED) dry eye questionnaires; tear break-up time was measured with the dry eye test (DET{\texttrademark}); and meibomian gland function was evaluated using a standardized diagnostic expression technique. Data are presented for patient{\textquoteright}s pre-treatment (baseline) and at 1-month and 9-month post-treatment. RESULTS: Meibomian gland secretion scores improved significantly from baseline (4.4 {\textpm} 4.0) to 1-month post-treatment (11.3 {\textpm} 6.2; p \&lt; 0.0001) and this improvement was maintained with no significant regression at 9 months (11.7 {\textpm} 5.9). Similarly, baseline tear break-up time (4.8 {\textpm} 3.2) was significantly increased at 1 month (9.6 {\textpm} 7.6; p \&lt; 0.001) and this increase was maintained with no significant regression at 9 months (7.1 {\textpm} 5.6). Symptom scores on both OSDI and SPEED questionnaires improved significantly at 1 month (p \&lt; 0.0001) and this improvement was maintained at 9 months. CONCLUSION: With such prolonged improvement in signs and symptoms of dry eye disease, the LipiFlow({\textregistered}) Thermal Pulsation System offers a technological advancement for the treatment of dry eye disease secondary to meibomian gland dysfunction. A single 12-minute LipiFlow({\textregistered}) treatment results in up to 9 months of sustained improvement of meibomian gland function, tear break-up time and dry eye symptoms that are unparalleled with current dry eye treatments.},
	keywords = {Dry Eye Syndromes, Equipment Design, Female, Follow-Up Studies, Humans, Hyperthermia, Induced, Male, Meibomian Glands, Middle Aged, Prospective Studies, Surveys and Questionnaires, Tears, Treatment Outcome},
	issn = {1460-2202},
	doi = {10.3109/02713683.2011.631721},
	author = {Greiner, Jack V}
}
@article {503981,
	title = {Long-Term (3 Year) Effects of a Single Thermal Pulsation System Treatment on Meibomian Gland Function and Dry Eye Symptoms.},
	journal = {Eye Contact Lens},
	volume = {42},
	number = {2},
	year = {2016},
	month = {2016 Mar},
	pages = {99-107},
	abstract = {PURPOSE: The present study examined the long-term (3 years) effects of a single (12 min) thermal pulsation system (TPS) treatment on symptomatic patients with evaporative dry eye disease (DED) secondary to meibomian gland dysfunction (MGD). METHODS: In this prospective, cohort, observational, single-center study design, signs (meibomian gland secretion [MGS] scores and tear film breakup time [TBUT]) and symptoms (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED] questionnaires) were determined in 20 patients (40 eyes) with MGD and dry eye symptoms at baseline (BL), 1 month, and 3 years post-TPS treatment using LipiFlow. RESULTS: Meibomian gland secretion scores increased from BL (4.5{\textpm}0.8) to 1 month (12.0{\textpm}1.1, P<=0.001). Improvement persisted at 3 years (18.4{\textpm}1.4) relative to BL (P<=0.001). Meibomian gland secretion scores in all regions of the lower eyelid were improved over BL at 1 month (nasal [P<=0.001], central [P<=0.001], temporal [P<=0.01]) and 3 years (nasal [P<=0.001], central [P<=0.001], temporal [P<=0.001]). TBUT increased from BL (4.1{\textpm}0.4) to 1 month (7.9{\textpm}1.4, P<=0.05) but was not significantly different than BL at 3 years (4.5{\textpm}0.6, P\&gt;0.05). The OSDI scores decreased from BL (26.0{\textpm}4.6) to 1 month (14.7{\textpm}4.3, P<=0.001) but returned to BL levels at 3 years (22.5{\textpm}5.4, P\&gt;0.05). The SPEED scores decreased from BL (13.4{\textpm}1.0) to 1 month (6.5{\textpm}1.3, P<=0.001), and this improvement persisted at 3 years (9.5{\textpm}1.6, P<=0.001). CONCLUSIONS: Thermal pulsation may be a uniquely efficacious treatment option for DED secondary to MGD in that a single 12-min procedure is associated with significant improvement in MGS and SPEED scores for up to 3 years.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000166},
	author = {Greiner, Jack V}
}
@article {1282116,
	title = {Meesmann epithelial corneal dystrophy: recurrence following photorefractive keratectomy},
	journal = {Can J Ophthalmol},
	volume = {52},
	number = {6},
	year = {2017},
	month = {2017 Dec},
	pages = {e211-e213},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2017.05.009},
	author = {Greiner, Jack V and Lindsay, Michael E and Kenyon, Kenneth R and Herman, John P and Reddy, Chaitanya V}
}
@article {1773596,
	title = {Adenosine Triphosphate (ATP) and Protein Aggregation in Age-Related Vision-Threatening Ocular Diseases},
	journal = {Metabolites},
	volume = {13},
	number = {10},
	year = {2023},
	month = {2023 Oct 20},
	abstract = {Protein aggregation is the etiopathogenesis of the three most profound vision-threatening eye diseases: age-related cataract, presbyopia, and age-related macular degeneration. This perspective organizes known information on ATP and protein aggregation with a fundamental unrecognized function of ATP. With recognition that maintenance of protein solubility is related to the high intracellular concentration of ATP in cells, tissues, and organs, we hypothesize that (1) ATP serves a critical molecular function for organismal homeostasis of proteins and (2) the hydrotropic feature of ATP prevents pathological protein aggregation while assisting in the maintenance of protein solubility and cellular, tissue, and organismal function. As such, the metabolite ATP plays an extraordinarily important role in the prevention of protein aggregation in the leading causes of vision loss or blindness worldwide.},
	issn = {2218-1989},
	doi = {10.3390/metabo13101100},
	author = {Greiner, Jack V and Glonek, Thomas}
}
@article {1474221,
	title = {Corneal Cryopreservation Using Glycerylphosphorylcholine-Enriched Medium},
	journal = {Cornea},
	volume = {39},
	number = {3},
	year = {2020},
	month = {2020 Mar},
	pages = {370-375},
	abstract = {PURPOSE: To determine the effects of prolonged cryopreservation at subzero-degree temperatures on corneal transparency and histology after treatment with preservation medium containing the phosphodiester glycerylphosphorylcholine (GPC). METHODS: Rabbit corneas (n = 30) were immersed for 3 hours in K-Sol preservation medium containing 30 mM GPC. Three groups with 6 corneas each were refrigerated at -8{\textdegree}C for 2 weeks and liquid nitrogen temperature for 2 and 6 weeks, respectively. Two groups with 6 corneas each immersed in K-Sol preservation medium only were refrigerated at -8{\textdegree}C for 2 weeks and liquid nitrogen temperature for 6 weeks, respectively. Postthawing corneal transparency was measured on a grading scale after which corneas were prepared for and analyzed by light and transmission electron microscopy. RESULTS: All 3 groups of corneas preserved with GPC maintained a greater degree of corneal transparency compared with corneas preserved without GPC. The number of corneas retaining epithelial and endothelial layers increased in all groups where corneas were preserved in medium containing GPC, in contrast to corneas preserved in medium without GPC. Cytoplasmic vacuolization or nuclear damage was greater in corneas preserved without GPC. Similar findings were found in corneas stored at -8{\textdegree}C and liquid nitrogen temperatures. CONCLUSIONS: This study demonstrates a cryoprotective effect of corneas preserved in K-Sol containing the phosphodiester GPC at subzero-degree temperatures. In corneas immersed in preservation medium containing GPC, a higher degree of transparency is maintained and a lesser degree of histopathologic changes is observed with storage at both -8{\textdegree}C and in liquid nitrogen.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002214},
	author = {Greiner, Jack V and Glonek, Thomas and Korb, Donald R and Lindsay, Michael E and Oliver, Paula J and Olson, Mary Catherine D}
}
@article {603931,
	title = {Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV.},
	journal = {Am J Pathol},
	volume = {186},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {199-209},
	abstract = {Mucolipidosis IV is a debilitating developmental lysosomal storage disorder characterized by severe neuromotor retardation and progressive loss of vision, leading to blindness by the second decade of life. Mucolipidosis IV is caused by loss-of-function mutations in the MCOLN1 gene, which encodes the transient receptor potential channel protein mucolipin-1. Ophthalmic pathology in patients includes corneal haze and progressive retinal and optic nerve atrophy. Herein, we report ocular pathology in Mcoln1(-/-) mouse, a good phenotypic model of the disease. Early, but non-progressive, thinning of the photoreceptor layer, reduced levels of rhodopsin, disrupted rod outer segments, and widespread accumulation of the typical storage inclusion bodies were the major histological findings in the Mcoln1(-/-) retina. Electroretinograms showed significantly decreased functional response (scotopic a- and b-wave amplitudes) in the Mcoln1(-/-) mice. At the ultrastructural level, we observed formation of axonal spheroids and decreased density of axons in the optic nerve of the aged (6-month-old) Mcoln1(-/-) mice, which indicates progressive axonal degeneration. Our data suggest that mucolipin-1 plays a role in postnatal development of photoreceptors and provides a set of outcome measures that can be used for ocular therapy development for mucolipidosis IV.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2015.09.017},
	author = {Grishchuk, Yulia and Stember, Katherine G and Matsunaga, Aya and Olivares, Ana M and Cruz, Nelly M and King, Victoria E and Humphrey, Daniel M and Wang, Shirley L and Muzikansky, Alona and Betensky, Rebecca A and Thoreson, Wallace B and Haider, Neena and Slaugenhaupt, Susan A}
}
@article {1354340,
	title = {Chalazia associated with bortezomib therapy for multiple myeloma},
	journal = {Ophthalmology},
	volume = {121},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1845-7.e3},
	keywords = {Aged, Antineoplastic Agents, Boronic Acids, Bortezomib, Chalazion, Female, Humans, Male, Middle Aged, Multiple Myeloma, Pyrazines, Retrospective Studies},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.04.021},
	author = {Grob, Seanna R and Jakobiec, Frederick A and Rashid, Alia and Yoon, Michael K}
}
@article {635006,
	title = {Central Retinal Vein Occlusion Resolving After Orbital Decompression in Thyroid Eye Disease.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2016},
	month = {2016 Jan 22},
	abstract = {A 49-year-old male presented with proptosis and was found to have optic nerve edema with peripapillary hemorrhages. Diagnostic testing showed a suppressed thyroid-stimulating hormone. CT orbits showed homogenous tendon-sparing enlargement of the medial and inferior rectus muscles, characteristic of thyroid eye disease. Intravenous methylprednisolone was administered given the concern for compressive optic neuropathy. He initially had improvement of his symptoms, so orbital decompression was deferred. Subsequently he presented with worsening diplopia and right proptosis, a new afferent pupillary defect, and a cecocentral visual field defect. Dilated examination revealed significant optic nerve head edema and diffuse retinal hemorrhages in all 4 quadrants consistent with a central retinal vein occlusion. The patient underwent an urgent 3-wall orbital decompression on the right. Close follow up postoperatively showed resolution of the central retinal vein occlusion and the associated optic disc edema, peripapillary hemorrhages, and macular edema. Orbital decompression is known to improve many manifestations of thyroid eye disease, but this is the first report of orbital decompression resulting in resolution of a central retinal vein occlusion.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000635},
	author = {Grob, Seanna R and Yoon, Michael K}
}
@article {504051,
	title = {Diffuse Epibulbar Complex Lacrimal-Cartilaginous Choristoma: Diagnostic Clues and Management.},
	journal = {Cornea},
	volume = {34},
	number = {10},
	year = {2015},
	month = {2015 Oct},
	pages = {1321-3},
	abstract = {PURPOSE: To describe the clinical and histopathologic features distinguishing an extensive complex choristoma of the epibulbar surface and to address the management of such lesions. METHODS: Clinical history, diagnostic imaging studies, and histopathologic sections stained with hematoxylin and eosin were reviewed from a 2-year-old girl with a congenital conjunctival lesion of the right eye that was surgically excised. RESULTS: The patient clinically displayed an extensive, vascularized amelanotic conjunctival lesion located superotemporally with extension onto the cornea. Her visual acuity was reduced to 20/670. The clinical diagnosis was a large lacrimal gland choristoma with corneal involvement and resulting deprivation amblyopia. The patient underwent an excision of the lesion including the corneal portion, and the ocular surface was reconstructed with amniotic membrane. Histopathologic evaluation disclosed lobules of lacrimal tissue and cartilage plaques, smooth muscle, and nerves consistent with a complex choristoma. Six weeks postoperatively, the visual acuity had improved to 20/180. The patient returned to her local ophthalmologist for amblyopia management. CONCLUSIONS: We emphasize the importance of recognizing lesion-induced amblyopia and the timely performance of appropriate surgery for complex epibulbar choristomas. A differential diagnosis of other congenital epibulbar lesions is provided.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000517},
	author = {Grob, Seanna R and Jakobiec, Frederick A and Stagner, Anna M and Colby, Kathryn A}
}
@article {468926,
	title = {Hemorrhage Within the Optic Nerve From a Cavernous Hemangioma of the Optic Disc.},
	journal = {J Neuroophthalmol},
	volume = {35},
	number = {3},
	year = {2015},
	month = {2015 Sep},
	pages = {277-9},
	abstract = {A 49-year-old woman with a known right optic disc cavernous hemangioma experienced pain with eye movements and worsening of a superior visual field defect. While she retained 20/20 visual acuity in each eye, findings on magnetic resonance imaging were consistent with a hemorrhage in the anterior portion of the right intraorbital optic nerve. Her visual function stabilized spontaneously. We are unaware of previous reports of hemorrhage into the optic nerve from a cavernous hemangioma of the optic disc.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000274},
	author = {Grob, Seanna R and Campbell, Ashley A and Gross, Andrew and Cestari, Dean M}
}
@article {369066,
	title = {Pediatric Optic Nerve Meningioma: Diagnostic and Therapeutic Challenges.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 Jan 12},
	abstract = {A 13-year-old female presented with left unilateral proptosis, blurry vision, and diplopia. Clinical examination showed left sided visual acuity of 20/50, limited extraocular movement, 5-mm proptosis, and optic disc edema. CT and MRI displayed a large, intraconal, well-demarcated soft tissue mass with inferotemporal displacement of the optic nerve. The imaging appearance was unusual and diagnosis remained uncertain. Histopathologic analysis of the biopsy specimen confirmed the diagnosis of atypical syncytial meningioma. The tumor cells were positive for both androgen and progesterone receptors and the Ki67 stain was positive (proliferation index of 8\%). The patient was treated with proton beam radiation therapy (total dose 50.4 GyE) that suppressed tumor growth and has preserved visual acuity to date (20/40). Differential diagnosis and approaches to therapy are explored.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000357},
	author = {Grob, Seanna R and Jakobiec, Frederick A and Rashid, Alia and MacIntosh, Peter and Kelly, Hillary and Fay, Aaron}
}
@article {1328881,
	title = {Osseous cavernous hemangioma of the superior orbital rim},
	journal = {Orbit},
	volume = {38},
	number = {3},
	year = {2019},
	month = {2019 Jun},
	pages = {259},
	abstract = {A 53-year-old male presented with a bony lesion over the superior orbital rim increasing in size over several months. CT imaging showed a circumscribed, osseous lesion involving the outer table of the right frontal bone and superior orbital rim with a honeycomb appearance. Anterior orbitotomy revealed an osseous lesion along the superior orbital rim with purple cavernous spaces. Histopathological examination demonstrated cavernous vascular channels with variably-sized lumens and variably-thickened vascular walls interspersed among bony trabeculae consistent with an osseous cavernous hemangioma.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2018.1509099},
	author = {Grob, Seanna R and Wolkow, Natalie and Jakobiec, Frederick A and Lefebvre, Daniel R}
}
@article {1354339,
	title = {Multimodal imaging of adult-onset foveomacular vitelliform dystrophy},
	journal = {Saudi J Ophthalmol},
	volume = {28},
	number = {2},
	year = {2014},
	month = {2014 Apr},
	pages = {104-10},
	abstract = {Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a clinically heterogeneous maculopathy that may mimic other conditions and be difficult to diagnose. It is characterized by late onset, slow progression and high variability in morphologic and functional alterations. Diagnostic evaluation should include careful ophthalmoscopy and imaging studies. The typical ophthalmoscopic findings are bilateral, asymmetric, foveal or perifoveal, yellow, solitary, round to oval elevated subretinal lesions, often with central pigmentation. The lesions characteristically demonstrate increased autofluorescence and hypofluorescent lesions surrounded by irregular annular hyperfluorescence on fluorescein angiography. Optical coherence tomography studies demonstrate homogenous or heterogeneous hyperreflective material between the retinal pigment epithelium and the neurosensory retina. The visual prognosis is generally favorable, but visual loss can occur from chorioretinal atrophy and choroidal neovascularization.},
	issn = {1319-4534},
	doi = {10.1016/j.sjopt.2014.02.001},
	author = {Grob, Seanna and Yonekawa, Yoshihiro and Eliott, Dean}
}
@article {313126,
	title = {Management of mydriasis and pain in cataract and intraocular lens surgery: review of current medications and future directions.},
	journal = {Clin Ophthalmol},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {1281-9},
	abstract = {The maintenance of mydriasis and the control of postoperative pain and inflammation are critical to the safety and success of cataract and intraocular lens replacement surgery. Appropriate mydriasis is usually achieved by topical and/or intracameral administration of anticholinergic agents, sympathomimetic agents, or both, with the most commonly used being cyclopentolate, tropicamide, and phenylephrine. Ocular inflammation is common after cataract surgery. Topical steroids and nonsteroidal anti-inflammatory drugs are widely used because they have been proved effective to control postsurgical inflammation and decrease pain. Topical nonsteroidal anti-inflammatory drugs have also been shown to help maintain dilation. However, use of multiple preoperative drops for pupil dilation, inflammation, and pain control have been shown to be time consuming, resulting in delays to the operating room, and they cause dissatisfaction among perioperative personnel; their use can also be associated with systemic side effects. Therefore, ophthalmologists have been in search of new options to streamline this process. This article will review the current medications commonly used for intraoperative mydriasis, as well as pain and inflammation control. In addition, a new combination of ketorolac, an anti-inflammatory agent, and phenylephrine, a mydriatic agent has recently been designed to maintain intraoperative mydriasis and to reduce postoperative pain and irritation from intraocular lens replacement surgery. Two Phase III clinical trials evaluating this combination have demonstrated statistically significant differences when compared to placebo in maintaining intraoperative mydriasis (P\&lt;0.00001) and in reducing pain in the early postoperative period (P=0.0002). This medication may be of benefit for use in cataract and lens replacement surgery in the near future.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S47569},
	author = {Grob, Seanna R and Gonzalez-Gonzalez, Luis A and Daly, Mary K}
}
@article {882931,
	title = {Lacrimal Gland Repair Using Progenitor Cells.},
	journal = {Stem Cells Transl Med},
	year = {2016},
	month = {2016 Aug 15},
	abstract = {: In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film. Production of tears in insufficient quantity or of inadequate quality may lead to aqueous-deficiency dry eye (ADDE). Currently there is no cure for ADDE. The development of strategies to reliably isolate LG stem/progenitor cells from the LG tissue brings great promise for the design of cell replacement therapies for patients with ADDE. We analyzed the therapeutic potential of epithelial progenitor cells (EPCPs) isolated from adult wild-type mouse LGs by transplanting them into the LGs of TSP-1(-/-) mice, which represent a novel mouse model for ADDE. TSP-1(-/-) mice are normal at birth but progressively develop a chronic form of ocular surface disease, characterized by deterioration, inflammation, and secretory dysfunction of the lacrimal gland. Our study shows that, among c-kit-positive epithelial cell adhesion molecule (EpCAM(+)) populations sorted from mouse LGs, the c-kit(+)dim/EpCAM(+)/Sca1(-)/CD34(-)/CD45(-) cells have the hallmarks of an epithelial cell progenitor population. Isolated EPCPs express pluripotency factors and markers of the epithelial cell lineage Runx1 and EpCAM, and they form acini and ducts when grown in reaggregated three-dimensional cultures. Moreover, when transplanted into injured or "diseased" LGs, they engraft into acinar and ductal compartments. EPCP-injected TSP-1(-/-) LGs showed reduction of cell infiltration, differentiation of the donor EPCPs within secretory acini, and substantial improvement in LG structural integrity and function. This study provides the first evidence for the effective use of adult EPCP cell transplantation to rescue LG dysfunction in a model system. SIGNIFICANCE: In humans, the lacrimal gland is the primary contributor to the aqueous layer of the tear film. Damage or inflammation of the lacrimal gland may lead to severe aqueous-deficiency dry eye and corneal disease. Endogenous lacrimal gland epithelial cell progenitors (EPCPs) injected into the gland of mouse model of human Sj{\"o}gren{\textquoteright}s syndrome TSP-1(-/-) mice resulted in long-term engraftment and markedly improved structure and function of "diseased" lacrimal gland. This study demonstrates, for the first time, that EPCPs can mediate functional recovery of the lacrimal gland in a Sj{\"o}gren{\textquoteright}s syndrome mouse model. These data establish proof of concept that endogenous stem/progenitor cell transplantation may be used to treat human lacrimal gland chronic inflammation.},
	issn = {2157-6564},
	doi = {10.5966/sctm.2016-0191},
	author = {Gromova, Anastasia and Voronov, Dmitry A and Yoshida, Miya and Thotakura, Suharika and Meech, Robyn and Dartt, Darlene A. and Makarenkova, Helen P}
}
@article {1323923,
	title = {Five-Year Outcomes of Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {10},
	year = {2018},
	month = {2018 Oct 01},
	pages = {1138-1148},
	abstract = {Importance: Ranibizumab is a viable treatment option for eyes with proliferative diabetic retinopathy (PDR) through 2 years. However, longer-term results are needed. Objective: To evaluate efficacy and safety of 0.5-mg intravitreous ranibizumab vs panretinal photocoagulation (PRP) over 5 years for PDR. Design, Setting, and Participants: Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial evaluated 394 study eyes with PDR enrolled February through December 2012. Analysis began in January 2018. Interventions: Eyes were randomly assigned to receive intravitreous ranibizumab (n = 191) or PRP (n = 203). Frequency of ranibizumab was based on a protocol-specified retreatment algorithm. Diabetic macular edema could be managed with ranibizumab in either group. Main Outcomes and Measures: Mean change in visual acuity (intention-to-treat analysis) was the main outcome. Secondary outcomes included peripheral visual field loss, development of vision-impairing diabetic macular edema, and ocular and systemic safety. Results: The 5-year visit was completed by 184 of 277 participants (66\% excluding deaths). Of 305 enrolled participants, the mean (SD) age was 52 (12) years, 135 (44\%) were women, and 160 (52\%) were white. For the ranibizumab and PRP groups, the mean (SD) number of injections over 5 years was 19.2 (10.9) and 5.4 (7.9), respectively; the mean (SD) change in visual acuity letter score was 3.1 (14.3) and 3.0 (10.5) letters, respectively (adjusted difference, 0.6; 95\% CI, -2.3 to 3.5; P = .68); the mean visual acuity was 20/25 (approximate Snellen equivalent) in both groups at 5 years. The mean (SD) change in cumulative visual field total point score was -330 (645) vs -527 (635) dB in the ranibizumab (n = 41) and PRP (n = 38) groups, respectively (adjusted difference, 208 dB; 95\% CI, 9-408). Vision-impairing diabetic macular edema developed in 27 and 53 eyes in the ranibizumab and PRP groups, respectively (cumulative probabilities: 22\% vs 38\%; hazard ratio, 0.4; 95\% CI, 0.3-0.7). No statistically significant differences between groups in major systemic adverse event rates were identified. Conclusions and Relevance: Although loss to follow-up was relatively high, visual acuity in most study eyes that completed follow-up was very good at 5 years and was similar in both groups. Severe vision loss or serious PDR complications were uncommon with PRP or ranibizumab; however, the ranibizumab group had lower rates of developing vision-impairing diabetic macular edema and less visual field loss. Patient-specific factors, including anticipated visit compliance, cost, and frequency of visits, should be considered when choosing treatment for patients with PDR. These findings support either anti-vascular endothelial growth factor therapy or PRP as viable treatments for patients with PDR. Trial Registration: ClinicalTrials.gov Identifier: NCT01489189.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.3255},
	author = {Gross, Jeffrey G and Glassman, Adam R and Liu, Danni and Sun, Jennifer K and Antoszyk, Andrew N and Baker, Carl W and Bressler, Neil M and Elman, Michael J and Ferris, Frederick L and Gardner, Thomas W and Jampol, Lee M and Martin, Daniel F and Melia, Michele and Stockdale, Cynthia R and Beck, Roy W and Diabetic Retinopathy Clinical Research Network}
}
@article {961706,
	title = {Association of Low Vitamin D Levels With Noninfectious Anterior Uveitis.},
	journal = {JAMA Ophthalmol},
	year = {2016},
	month = {2016 Dec 22},
	abstract = {Importance: Vitamin D plays an important role in both the innate and adaptive immune systems. It has been shown to contribute to the etiology of T-cell-mediated autoimmune diseases through the upregulation of type 2 anti-inflammatory T helper cells and the suppression of type 1 T helper cells. Noninfectious uveitis is postulated to be caused by immune dysfunction. Objective: To determine whether there is an association between vitamin D levels and noninfectious anterior uveitis. Design, Setting, and Participants: This was a case-control study. We identified patients with and without noninfectious uveitis using the Massachusetts Eye and Ear Infirmary Ocular Inflammation Database and electronic medical records from March 1, 2008, to December 12, 2015, at the Massachusetts Eye and Ear Infirmary Uveitis and Comprehensive Ophthalmology Clinics. One hundred patients with noninfectious anterior uveitis and 100 patients without uveitis were recruited. Patients with noninfectious uveitis were diagnosed by fellowship-trained uveitis specialists after exclusion of infectious causes and neoplastic masquerades of uveitis. All patients included had a total 25-hydroxyvitamin D level recorded. Multivariate regression models were constructed to determine the association between vitamin D levels and the presence of uveitis. Main Outcome and Measure: Presence of noninfectious anterior uveitis. Results: We identified 100 patients (64 white, 8 African American, 25 Asian, and 3 Hispanic) with a mean (SD) age of 51.8 (15.9) years (26 men) and 100 control individuals (58 white, 23 African American, 8 Asian, and 11 Hispanic) with a mean (SD) age of 53.6 (16.2) years (27 men). Hypovitaminosis D was associated with noninfectious uveitis in the univariate analysis (odds ratio, 2.53; 95\% CI, 1.42-4.51; P = .002). The association in multivariate regression after adjusting for age, sex, and race/ethnicity was 2.96 (95\% CI, 1.60-5.50; P = .001) The odds of developing uveitis were 4\% lower for every 1-ng/mL increase in vitamin D level (odds ratio, 0.96; 95\% CI, 0.93-0.99; P = .01) in the main multivariate analysis. Conclusions and Relevance: In this retrospective study, lower vitamin D levels were associated with an increased risk of noninfectious anterior uveitis. However, this does not confirm a causal effect.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.4888},
	author = {Grotting, Lindsay A and Davoudi, Samaneh and Palenzuela, Deanna and Papaliodis, George N and Sobrin, Lucia}
}
@article {1125306,
	title = {Pre-papillary vitreous opacities associated with Beh{\c c}et{\textquoteright}s disease: a case series and review of the literature},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	year = {2017},
	month = {2017 Jul 19},
	abstract = {PURPOSE: To present pre-papillary vitreous opacity as an uncommon manifestation of inflammation in Beh{\c c}et{\textquoteright}s disease that may be specific to this uveitic entity. METHODS: We retrospectively reviewed the charts of 67 patients with Beh{\c c}et{\textquoteright}s disease examined at our clinic between 2005 and 2016. Beh{\c c}et{\textquoteright}s disease was diagnosed based on established clinical criteria of inflammation involving the eyes, mucocutaneous junctions, and skin. Patients with Beh{\c c}et{\textquoteright}s disease who presented with papillitis and a pre-papillary vitreous opacity were identified. Response to anti-inflammatory treatment on examination and optical coherence tomography imaging were evaluated. PubMed searches were performed for (1) other cases with pre-papillary vitreous opacities in uveitic entities and (2) reports of optic nerve involvement specifically in Beh{\c c}et{\textquoteright}s disease. RESULTS: We identified three patients with Beh{\c c}et{\textquoteright}s disease who presented with unilateral papillitis and a pre-papillary vitreous opacity. The pre-papillary vitreous opacity had a funnel-shaped appearance on optical coherence tomography. All patients were initially treated with steroids, which led to resolution of the opacity clinically and on imaging. We identified one previous report of such a pre-papillary opacity in a patient with Beh{\c c}et{\textquoteright}s disease, and no reports of this finding in other uveitic entities. CONCLUSION: This study expands the number of Beh{\c c}et{\textquoteright}s disease cases presenting with a pre-papillary vitreous opacity and demonstrates novel optical coherence imaging of this finding. This finding may be specific to Beh{\c c}et{\textquoteright}s disease as it was not identified in other uveitic entities in a review of the existing literature.},
	issn = {1435-702X},
	doi = {10.1007/s00417-017-3741-7},
	author = {Grotting, Lindsay A and Davoudi, Samaneh and Uchiyama, Eduardo and Lobo, Ann-Marie and Papaliodis, George N and Sobrin, Lucia}
}
@article {1635653,
	title = {Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes},
	journal = {EMBO Mol Med},
	volume = {14},
	number = {4},
	year = {2022},
	month = {2022 Apr 07},
	pages = {e14817},
	abstract = {Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in\&nbsp;vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in\&nbsp;vivo.},
	keywords = {Animals, Cell Cycle Proteins, Cytoskeletal Proteins, Humans, Photoreceptor Cells, Swine, Usher Syndromes},
	issn = {1757-4684},
	doi = {10.15252/emmm.202114817},
	author = {Grotz, Sophia and Sch{\"a}fer, Jessica and Wunderlich, Kirsten A and Ellederova, Zdenka and Auch, Hannah and B{\"a}hr, Andrea and Runa-Vochozkova, Petra and Fadl, Janet and Arnold, Vanessa and Ardan, Taras and Veith, Miroslav and Santamaria, Gianluca and Dhom, Georg and Hitzl, Wolfgang and Kessler, Barbara and Eckardt, Christian and Klein, Joshua and Brymova, Anna and Linnert, Joshua and Kurome, Mayuko and Zakharchenko, Valeri and Fischer, Andrea and Blutke, Andreas and D{\"o}ring, Anna and Suchankova, Stepanka and Popelar, Jiri and Rodr{\'\i}guez-Bocanegra, Eduardo and Dlugaiczyk, Julia and Straka, Hans and May-Simera, Helen and Wang, Weiwei and Laugwitz, Karl-Ludwig and Vandenberghe, Luk H and Wolf, Eckhard and Nagel-Wolfrum, Kerstin and Peters, Tobias and Motlik, Jan and Fischer, M Dominik and Wolfrum, Uwe and Klymiuk, Nikolai}
}
@article {603941,
	title = {Effects of Prior Intensive Insulin Therapy and Risk Factors on Patient-Reported Visual Function Outcomes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort.},
	journal = {JAMA Ophthalmol},
	year = {2015},
	month = {2015 Nov 19},
	pages = {1-10},
	abstract = {Importance: Preservation of vision in patients with diabetes mellitus is critical. Interventions to improve glycemic control through early intensive treatment of diabetes reduce rates of severe retinopathy and preserve visual acuity. Objective: To assess the effects of prior intensive insulin treatment and risk factors on patient-reported visual function in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Design, Setting, and Participants: Cohort study of 1184 participants with type 1 diabetes from the DCCT/EDIC study (randomized clinical trial followed by an observational follow-up study) who completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) during EDIC years 17 through 20 (September 1, 2009, through April 30, 2014) in 28 institutions across the United States and Canada. Main Outcomes and Measures: The primary outcome was the composite NEI-VFQ-25 score. Secondary outcomes were visual acuity (measured by the Early Treatment Diabetic Retinopathy Study protocol), retinopathy level (determined by masked grading of stereoscopic color fundus photographs), and NEI-VFQ-25 subscale scores. The composite NEI-VFQ-25 scale and its subscales were scored 0 to 100, corresponding to poor to excellent function, respectively. Results: The overall average NEI-VFQ-25 score for 1184 DCCT/EDIC participants (mean [SD] age, 52.3 [6.9] years; 48\% female) with a 30-year duration of diabetes was high (all participants: median, 91.7; interquartile range [IQR], 89.7-96.9; intensive treatment [n = 605]: median, 94.7; IQR, 91.0-97.2; conventional treatment [n = 579]: median, 94.0; IQR, 88.4-96.1; P = .006 for intensive vs conventional). After adjustment for sex, age, hemoglobin A1c level, and retinopathy level at DCCT baseline, the former intensive treatment group had a significant, albeit modest, improvement in overall NEI-VFQ-25 score compared with the former conventional diabetes treatment group (median difference, -1.0; 95\% CI, -1.7 to -0.3; P = .006). This beneficial treatment effect was fully attributed to the prior glycemic control in DCCT (explained treatment effect: 100\%). Those with visual acuity worse than 20/100 reported the largest decline in visual function (median difference, -21.0; 95\% CI, -40.5 to -1.6; P = .03). Conclusions and Relevance: In the DCCT/EDIC cohort, patient-reported visual function remains high in both treatment groups, comparable to previous reports of overall health-related quality of life. Intensive diabetes therapy modestly improved NEI-VFQ-25 score 30 years after the start of the DCCT, the benefit underestimated owing to more nonparticipants from the conventional treatment group. Visual acuity had the greatest effect on patient-reported visual function from among all risk factors. Trial Registration: clinicaltrials.gov Identifiers: NCT00360815 and NCT00360893.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.4606},
	author = {Writing Team for the DCCT/EDIC Research Group and Gubitosi-Klug, Rose A and Sun, Wanjie and Cleary, Patricia A and Braffett, Barbara H and Aiello, Lloyd Paul and Das, Arup and Tamborlane, William and Klein, Ronald}
}
@article {1538322,
	title = {Assessment of Pediatric Optic Neuritis Visual Acuity Outcomes at 6 Months},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Oct 15},
	abstract = {Importance: Optic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample would be useful for counseling families on treatment decisions and prognosis. Objective: To prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network{\textquoteright}s (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively. Design, Setting, and Participants: This nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON. Main Outcomes and Measures: Primary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein. Results: A total of 44 children (mean age [SD], 10.2 [3.5] years; 26 boys [59\%]; 23 White individuals [52\%]; 54 eyes) were enrolled in the study. Sixteen patients (36\%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52\%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18\%), 7 had acute disseminated encephalomyelitis (16\%), 5 had multiple sclerosis (11\%), and 3 had neuromyelitis optica (7\%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95\% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95\% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged \&lt;10 years) with associated neurologic autoimmune diagnoses, white matter lesions, and in those of non-White race and non-Hispanic ethnicity. The data did not suggest a statistically significant association between baseline factors and improvement in HCVA. Conclusions and Relevance: The study network did not reach its targeted enrollment of 100 pediatric patients with ON over 2 years. This indicates that future treatment trials may need to use different inclusion criteria or plan a longer enrollment period to account for the rarity of the disease. Despite poor VA at presentation, most children had marked improvement by 6 months. Associated neurologic autoimmune diagnoses were common. These findings can be used to counsel families about the disease.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.4231},
	author = {Writing Committee for the Pediatric Eye Disease Investigator Group and Pineles, Stacy L and Repka, Michael X and Liu, Grant T and Waldman, Amy T and Borchert, Mark S and Khanna, Sangeeta and Heidary, Gena and Graves, Jennifer S and Shah, Veeral S and Kupersmith, Mark J and Kraker, Raymond T and Wallace, David K and Cotter, Susan A and Holmes, Jonathan M}
}
@article {1638579,
	title = {Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {4},
	year = {2022},
	month = {2022 Apr 01},
	pages = {337-344},
	abstract = {Importance: Intravitreal bevacizumab effectively treats severe retinopathy of prematurity (ROP), but it enters the bloodstream and may reduce serum vascular endothelial growth factor (VEGF), potentially causing detrimental effects on developing organs in the premature infant. Objective: To evaluate the association of intravitreal bevacizumab with plasma bevacizumab and VEGF concentrations at 2 and 4 weeks after predefined, de-escalating doses of intravitreal bevacizumab were administered to infants with severe ROP. Design, Setting, and Participants: This phase 1 dose de-escalation case series study was conducted at 10 US hospitals of ophthalmology institutions from May 21, 2015, to May 7, 2019. Blood samples were collected 2 and 4 weeks after intravitreal bevacizumab injection. Participants included 83 premature infants with type 1 ROP in 1 or both eyes and no previous ROP treatment. Data were analyzed from April 2017 to August 2021. Interventions: Study eyes received a single bevacizumab injection of 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. When the fellow eye required treatment, one dose higher was administered. Total dose administered at baseline was defined as the sum of doses given to each eye within 3 days of initial study-eye injection. Main Outcomes and Measures: Plasma bevacizumab concentration at 2 and 4 weeks after injection and the percentage change in plasma VEGF concentrations from pretreatment levels. Results: A total of 83 infants (mean [SD] age, 25 [2] weeks; 48 boys [58\%]) were included in this study. Higher doses of bevacizumab administered at baseline were associated with higher plasma bevacizumab concentrations at 2 weeks (ρ, 0.53; 95\% CI, 0.31-0.70) and 4 weeks (ρ, 0.44; 95\% CI, 0.18-0.64). Plasma VEGF concentrations decreased by 50\% or more from pretreatment levels in 40 of 66 infants (61\%) at 2 weeks and 31 of 61 infants (51\%) at 4 weeks, but no association was observed between the total dose of bevacizumab administered at baseline and percentage change in plasma VEGF concentrations 2 weeks (ρ, -0.04; 95\% CI, -0.28 to 0.20) or 4 weeks (ρ, -0.17; 95\% CI, -0.41 to 0.08) after injection. Conclusions and Relevance: Results of this phase 1 dose de-escalation case series study revealed that bevacizumab doses as low as 0.002 mg were associated with reduced plasma VEGF levels for most infants at 2 and 4 weeks after intravitreal administration; however, no association was observed between total bevacizumab dose administered and reductions in plasma VEGF levels from preinjection to 2 weeks or 4 weeks. Additional studies are needed to evaluate the long-term effects of low-dose bevacizumab on neurodevelopment and retinal structure.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Female, Gestational Age, Humans, Infant, Infant, Newborn, Intravitreal Injections, Male, Retinopathy of Prematurity, Vascular Endothelial Growth Factor A},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.0030},
	author = {Writing Committee for the Pediatric Eye Disease Investigator Group and Hartnett, M Elizabeth and Wallace, David K and Dean, Trevano W and Li, Zhuokai and Boente, Charline S and Dosunmu, Eniolami O and Freedman, Sharon F and Golden, Richard P and Kong, Lingkun and Prakalapakorn, S Grace and Repka, Michael X and Smith, Lois E and Wang, Haibo and Kraker, Raymond T and Cotter, Susan A and Holmes, Jonathan M}
}
@article {1078751,
	title = {Association Between Long-Lasting Intravitreous Fluocinolone Acetonide Implant vs Systemic Anti-inflammatory Therapy and Visual Acuity at 7 Years Among Patients With Intermediate, Posterior, or Panuveitis},
	journal = {JAMA},
	volume = {317},
	number = {19},
	year = {2017},
	month = {2017 May 16},
	pages = {1993-2005},
	abstract = {Importance: A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. Objective: To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis. Design, Setting, and Participants: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within <=60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). Interventions: Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. Main Outcomes and Measures: Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. Results: Seven-year data were obtained for 161 uveitic eyes (70\% of 90 patients assigned to implant) and 167 uveitic eyes (71\% of 90 patients assigned to systemic therapy) (77\% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95\% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10\%, with the exceptions of hyperlipidemia (6.1\% vs 11.2\%), hypertension (9.8\% vs 18.4\%), osteopenia (41.5\% vs 43.1\%), fractures (11.3\% vs 18.6\%), hospitalization (47.6\% vs 42.3\%), and antibiotic-treated infection (57.4\% vs 72.3\%). Conclusions and Relevance: In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT00132691.},
	issn = {1538-3598},
	doi = {10.1001/jama.2017.5103},
	author = {Writing Committee for the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group and Kempen, John H and Altaweel, Michael M and Holbrook, Janet T and Sugar, Elizabeth A and Thorne, Jennifer E and Jabs, Douglas A}
}
@article {1328882,
	title = {Retinal Parameters as Compared with Head Circumference, Height, Weight, and Body Mass Index in Children in Kenya and Bhutan},
	journal = {Am J Trop Med Hyg},
	volume = {99},
	number = {2},
	year = {2018},
	month = {2018 Aug},
	pages = {482-488},
	abstract = {The retina shares embryological derivation with the brain and may provide a new measurement of overall growth status, especially useful in resource-limited settings. Optical coherence tomography (OCT) provides detailed quantification of retinal structures. We enrolled community-dwelling children ages 3-11 years old in Siaya, Kenya and Thimphu, Bhutan in 2016. We measured head circumference (age \&lt; 5 years only), height, and weight, and standardized these by age and gender. Research staff performed OCT (; Optovue, Inc., Fremont, CA), measuring the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thicknesses. A neuro-ophthalmologist performed quality control for centration, motion artifact, and algorithm-derived quality scores. Generalized estimating equations were used to determine the relationship between anthropometric and retinal measurements. Two hundred and fifty-eight children (139 females, average age 6.4 years) successfully completed at least one retinal scan, totaling 1,048 scans. Nine hundred and twenty-two scans (88.0\%) were deemed usable. Fifty-three of the 258 children (20.5\%) were able to complete all six scans. Kenyan children had a thinner average GCC ( \&lt; 0.001) than Bhutanese children after adjustment for age and gender, but not RNFL ( = 0.70). In models adjusting for age, gender, and study location, none of standardized height, weight, and body mass index (BMI) were statistically significantly associated with RNFL or GCC. We determined that OCT is feasible in some children in resource-limited settings, particularly those \&gt; 4 years old, using the device. We found no evidence for GCC or RNFL as a proxy for height-, weight-, or BMI-for-age. The variation in mean GCC thickness in Asian versus African children warrants further investigation.},
	issn = {1476-1645},
	doi = {10.4269/ajtmh.17-0943},
	author = {Grundy, Sara J and Tshering, Lhab and Wanjala, Stanley W and Diamond, Megan B and Audi, Martin S and Prasad, Sashank and Shinohara, Russell T and Rogo, Debora and Wangmo, Dechen and Wangdi, Ugyen and Aarayang, Abi and Tshering, Thukten and Burke, Thomas F and Mateen, Farrah J}
}
@article {509151,
	title = {Temporal Artery Biopsy in Giant Cell Arteritis.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {10},
	year = {2015},
	month = {2015 Oct 1},
	pages = {1220},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.2552},
	author = {Grzybowski, Andrzej and Stacy, Rebecca C}
}
@article {1573102,
	title = {Central Endothelin-1 Confers Analgesia by Triggering Spinal Neuronal Histone Deacetylase 5 (HDAC5) Nuclear Exclusion in Peripheral Neuropathic Pain in Mice},
	journal = {J Pain},
	volume = {22},
	number = {4},
	year = {2021},
	month = {2021 Apr},
	pages = {454-471},
	abstract = {The rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. Here, we demonstrate that upregulating spinal ET-1 attenuated the nociception induced by partial sciatic nerve ligation surgery and this analgesic effect mediated by ET-1 was attenuated by intrathecal injection of endothelin A receptor selective inhibitor (BQ123) or by blocking the exportation of nuclear HDAC5 by adeno-associated viruses targeting neuronal HDAC5 (AVV-HDAC5 S259/498A Mutant). Notably, ET-1 administration increased spinal glutamate acid decarboxylases (GAD65/67) expression via initiating HDAC5 nuclear exportation and increased the acetylation of histone 3 at lysine 9 (Acetyl-H3K9) in the promotor regions of spinal Gad1 and Gad2 genes. This was reversed by blocking endothelin A receptor function or by inhibiting the spinal neuronal nuclear exportation of HDAC5. Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain. PERSPECTIVE: Neuropathic pain is intractable in a clinical setting, and epigenetic regulation is considered to contribute to this processing. Characterizing the anti-nociceptive effect of ET-1 and investigating the associated epigenetic mechanisms in animal models may lead to the development of new therapeutic strategies and targets for treating neuropathic pain.},
	issn = {1528-8447},
	doi = {10.1016/j.jpain.2020.12.004},
	author = {Gu, Pan and Fan, Tingting and Wong, Stanley Sau Ching and Pan, Zhiqiang and Tai, Wai Lydia and Chung, Sookja Kim and Cheung, Chi Wai}
}
@article {1632305,
	title = {Examining the Role of Early Diagnostic Imaging for Craniosynostosis in the Era of Endoscopic Suturectomy: A Single Institution Experience},
	journal = {J Craniofac Surg},
	year = {2022},
	month = {2022 Feb 08},
	abstract = {ABSTRACT: Endoscopic suturectomy is a minimally invasive surgical treatment for single-suture craniosynostosis in children between 1 and 4 months of age. This study sought to characterize the role played by diagnostic imaging in facilitating early surgical management with endoscopic suturectomy. The authors also characterized the overall diagnostic utility of imaging in patients assessed for abnormal head shape at their institution, regardless of surgical status. A retrospective cohort of children diagnosed with single-suture synostosis undergoing either primary endoscopic suturectomy or open calvarial reconstruction at the authors{\textquoteright} institution from 1998 to 2018 was first reviewed. Of 132 surgical patients, 53 underwent endoscopic suturectomy and 79 underwent open repair. There was no difference in the proportion of endoscopic and open surgery patients imaged preoperatively before (24.5\% versus 35.4\%; P = 0.24) or after (28.3\% versus 25.3\%; P = 0.84) craniofacial assessment. Stratifying by historical epoch (1998-2010 versus 2011-2018), there was also no difference found between preoperative imaging rates (63.6\% versus 56.4\%; P = 0.35). In another cohort of 175 patients assessed for abnormal head shape, 26.9\% were imaged to rule out craniosynostosis. Positive diagnostic imaging rates were recorded for suspected unicoronal (100\%), metopic (87.5\%), lambdoidal (75.0\%), sagittal (63.5\%), multi-suture (50\%), and bicoronal (0\%) synostosis. The authors conclude that the use of diagnostic imaging at their institution has not increased despite higher utilization of endoscopic suturectomy and need for expedient identification of surgical candidates. However, their results suggest that imaging may play a greater diagnostic role for suspected bicoronal, sagittal, and multi-sutural synostosis among sutural subtypes of synostosis.},
	issn = {1536-3732},
	doi = {10.1097/SCS.0000000000008534},
	author = {Guadix, Sergio W and Valenti, Alyssa and Zappi, Kyle E and Garton, Andrew L A and Yuan, Melissa and Buontempo, Michelle and Perera, Imali and Souweidane, Mark M and Imahiyerobo, Thomas and Hoffman, Caitlin E}
}
@article {1664988,
	title = {Defining Occult High-Risk Cysts of the Pineal Region: A Case Series},
	journal = {Oper Neurosurg (Hagerstown)},
	volume = {24},
	number = {6},
	year = {2023},
	month = {2023 Jun 01},
	pages = {572-581},
	abstract = {BACKGROUND: Absence of hydrocephalus on neuroimaging may impart a false sense of security for patients with pineal cysts. In this case series, we characterize a subset of patients with pineal cysts having an occult presentation. Unifying features of worsening paroxysmal headaches suggesting intermittent obstructive hydrocephalus and radiographic evidence of third ventricular invagination characterize these patients as high risk. OBJECTIVE: To define features of occult, high-risk pineal cysts and outcomes of endoscopic cyst fenestration. METHODS: Charts were retrospectively reviewed for patients with pineal cysts evaluated at our institution between 2018 and 2021 who underwent endoscopic cyst fenestration. To capture cysts presenting as occult, patients were excluded if hydrocephalus was noted at presentation. Relevant clinical history, imaging, operative data, and clinical outcomes were reviewed. RESULTS: Of 50 pineal cyst patients, 4 satisfied inclusion criteria. All patients presented with worsening paroxysmal headaches. In addition, 75\% (3/4) also experienced intermittent syncope. Patients exhibited no hydrocephalus (n = 3) or fluctuating ventricular size on longitudinal imaging (n = 1). In all cases, high-resolution sagittal 3-dimensional T2 magnetic resonance imaging demonstrated invagination of the cyst anteriorly into the posterior third ventricle. All patients underwent endoscopic cyst fenestration with complete symptom resolution (mean follow-up of 20.6 months; range 3.5-37.4 months). CONCLUSION: The clinical history for occult, high-risk pineal cysts is notable for worsening paroxysmal headaches and episodic alterations of consciousness suggesting intermittent obstructive hydrocephalus. Because ventricular size can appear normal on standard imaging protocols, clinical suspicion should trigger workup with high-resolution magnetic resonance imaging designed to detect these cysts. Endoscopic cyst fenestration is a safe and efficacious management strategy.},
	keywords = {Brain Neoplasms, Central Nervous System Cysts, Cysts, Headache, Humans, Hydrocephalus, Retrospective Studies},
	issn = {2332-4260},
	doi = {10.1227/ons.0000000000000620},
	author = {Guadix, Sergio W and Marianayagam, Neelan J and Weidman, Elizabeth K and Yuan, Melissa and Liechty, Benjamin and Greenfield, Jeffrey P and Souweidane, Mark M}
}
@article {1498239,
	title = {MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A},
	journal = {Front Pharmacol},
	volume = {11},
	year = {2020},
	month = {2020},
	pages = {276},
	abstract = {Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.},
	issn = {1663-9812},
	doi = {10.3389/fphar.2020.00276},
	author = {Guan, Ji-Tian and Li, Xin-Xin and Peng, De-Wei and Zhang, Wen-Meng and Qu, Jia and Lu, Fan and D{\textquoteright}Amato, Robert J and Chi, Zai-Long}
}
@article {1263341,
	title = {Systemic Manifestations in Pyridox(am)ine 5{\textquoteright}-Phosphate Oxidase Deficiency},
	journal = {Pediatr Neurol},
	volume = {76},
	year = {2017},
	month = {2017 Nov},
	pages = {47-53},
	abstract = {OBJECTIVE: Pyridoxine is converted to its biologically active form pyridoxal-5-phosphate (P5P) by the enzyme pyridox(am)ine 5{\textquoteright}-phosphate oxidase and serves as a cofactor in nearly 200 reactions in the central nervous system. Pyridox(am)ine 5{\textquoteright}-phosphate oxidase deficiency leads to P5P dependent epilepsy, typically a neonatal- or infantile-onset epileptic encephalopathy treatable with P5P or in some cases, pyridoxine. Following identification of retinopathy in a patient with pyridox(am)ine 5{\textquoteright}-phosphate oxidase deficiency that was reversible with P5P therapy, we describe the systemic manifestations of pyridox(am)ine 5{\textquoteright}-phosphate oxidase deficiency. METHODS: A series of six patients with homozygous mutations of PNPO, the gene coding pyridox(am)ine 5{\textquoteright}-phosphate oxidase, were evaluated in our center over the course of two years for phenotyping of neurological and systemic manifestations. RESULTS: Five of six were born prematurely, three had anemia and failure to thrive, and two had elevated alkaline phosphatase. A movement disorder was observed in two children, and a reversible retinopathy was observed in the most severely affected infant. All patients had neonatal-onset epilepsy and were on a continuum of developmental delay to profound encephalopathy. Electroencephalographic features included background slowing and disorganization, absent sleep features, and multifocal and generalized epileptiform discharges. All the affected probands carried a homozygous PNPO mutation (c.674\&nbsp;G\&gt;T, c.686\&nbsp;G\&gt;A and c.352G\&gt;A). CONCLUSION: In addition to the well-described epileptic encephalopathy, pyridox(am)ine 5{\textquoteright}-phosphate oxidase deficiency causes a range of neurological and systemic manifestations. A movement disorder, developmental delay, and encephalopathy, as well as retinopathy, anemia, and failure to thrive add to the broadening clinical spectrum of P5P dependent epilepsy.},
	issn = {1873-5150},
	doi = {10.1016/j.pediatrneurol.2017.05.024},
	author = {Guerriero, R{\'e}jean M and Patel, Archana A and Walsh, Brian and Baumer, Fiona M and Shah, Ankoor S and Peters, Jurriaan M and Rodan, Lance H and Agrawal, Pankaj B and Pearl, Phillip L and Takeoka, Masanori}
}
@article {1638550,
	title = {Looking through the scope: retinoblastoma in the Philippines},
	journal = {Eye (Lond)},
	volume = {36},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {2356-2357},
	keywords = {Humans, Philippines, Retinal Neoplasms, Retinoblastoma},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-02069-4},
	author = {Guevarra, Ma Carmela B and Eala, Michelle Ann B and Dee, Edward Christopher and Mercado, Gary John V and Collantes, Edward Ryan A}
}
@article {1307461,
	title = {Surgical adhesives in ophthalmology: history and current trends},
	journal = {Br J Ophthalmol},
	year = {2018},
	month = {2018 Mar 26},
	abstract = {Tissue adhesives are gaining popularity in ophthalmology, as they could potentially reduce the complications associated with current surgical methods. An ideal tissue adhesive should have superior tensile strength, be non-toxic and anti-inflammatory, improve efficiency and be cost-effective. Both synthetic and biological glues are available. The primary synthetic glues include cyanoacrylate and the recently introduced polyethylene glycol (PEG) derivatives, while most biological glues are composed of fibrin. Cyanoacrylate has a high tensile strength, but rapidly polymerises upon contact with any fluid and has been associated with histotoxicity. Fibrin induces less toxic and inflammatory reactions, and its polymerisation time can be controlled. Tensile strength studies have shown that fibrin is not as strong as cyanoacrylate. While more research is needed, PEG variants currently appear to have the most promise. These glues are non-toxic, strong and time-effective. Through MEDLINE and internet searches, this paper presents a systematic review of the current applications of surgical adhesives to corneal, glaucoma, retinal, cataract and strabismus surgeries. Our review suggests that surgical adhesives have promise to reduce problems in current ophthalmic surgical procedures.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2017-311643},
	author = {Guhan, Samantha and Peng, Si-Liang and Janbatian, Hrag and Saadeh, Stephanie and Greenstein, Stephen and Al Bahrani, Faisal and Fadlallah, Ali and Yeh, Tsai-Chu and Melki, Samir A}
}
@article {1773456,
	title = {KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3},
	journal = {Br J Ophthalmol},
	year = {2023},
	month = {2023 Oct 18},
	abstract = {BACKGROUND/AIMS: To investigate genotype-phenotype associations in patients with KCNV2 retinopathy. METHODS: Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants-two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)-and parameters were compared. RESULTS: Ninety-two patients were included. The mean age of onset (mean{\textpm}SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51{\textpm}0.58, 4.07{\textpm}2.76 and 5.54{\textpm}3.38 years, respectively. The mean LogMAR BCVA ({\textpm}SD) at baseline in TLOF, TM and MLOF groups was 0.89{\textpm}0.25, 0.67{\textpm}0.38 and 0.81{\textpm}0.35 for right, and 0.88{\textpm}0.26, 0.69{\textpm}0.33 and 0.78{\textpm}0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness ({\textpm}SD) at baseline in TLOF, MLOF and TM groups was 37.07{\textpm}15.20 {\textmu}m, 40.67{\textpm}12.53 and 40.38{\textpm}18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss ({\textpm}SD) was 2051 {\textmu}m ({\textpm}1318) for patients in the TLOF, and 1314 {\textmu}m ({\textpm}965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. CONCLUSIONS: Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.},
	issn = {1468-2079},
	doi = {10.1136/bjo-2023-323640},
	author = {de Guimaraes, Thales A C and Georgiou, Michalis and Robson, Anthony G and Fujinami, Kaoru and Vincent, Ajoy and Nasser, Fadi and Khateb, Samer and Mahroo, Omar A and Pontikos, Nikolas and Vargas, Maur{\'\i}cio E and Thiadens, Alberta A H J and de Carvalho, Emanuel R and Nguyen, Xuan-Than-An and Arno, Gavin and Fujinami-Yokokawa, Yu and Liu, Xiao and Tsunoda, Kazushige and Hayashi, Takaaki and Jim{\'e}nez-Rolando, Bel{\'e}n and Martin-Merida, Maria Inmaculada and Avila-Fernandez, Almudena and Salas, Ester Carre{\~n}o and Garcia-Sandoval, Blanca and Ayuso, Carmen and Sharon, Dror and Kohl, Susanne and Huckfeldt, Rachel M and Banin, Eyal and Pennesi, Mark E and Khan, Arif O and Wissinger, Bernd and Webster, Andrew R and Heon, Elise and Boon, Camiel J F and Zrenner, Eberhard and Michaelides, Michel}
}
@article {1642026,
	title = {Glycogene Expression Profile of Human Limbal Epithelial Cells with Distinct Clonogenic Potential},
	journal = {Cells},
	volume = {11},
	number = {9},
	year = {2022},
	month = {2022 May 07},
	abstract = {Glycans function as valuable markers of stem cells but also regulate the ability of these cells to self-renew and differentiate. Approximately 2\% of the human genome encodes for proteins that are involved in the biosynthesis and recognition of glycans. In the present study, we evaluated the expression of a small subset of glycogenes in human limbal epithelial cells with distinct clonogenic potential. Individual clones were classified as abortive or clonogenic, based on the fraction of the terminal colonies produced; clones leading exclusively to terminal colonies were referred to as abortive while those with half or fewer terminal colonies were referred to as clonogenic. An analysis of glycogene expression in clonogenic cultures revealed a high content of transcripts regulating the galactose and mannose metabolic pathways. Abortive clones were characterized by increased levels of GCNT4 and FUCA2, genes that are responsible for the branching of mucin-type O-glycans and the hydrolysis of fucose residues on N-glycans, respectively. The expansion of primary cultures of human limbal epithelial cells for 10 days resulted in stratification and a concomitant increase in MUC16, GCNT4 and FUCA2 expression. These data indicate that the clonogenic potential of human limbal epithelial cells is associated with specific glycosylation pathways. Mucin-type O-glycan branching and increased fucose metabolism are linked to limbal epithelial cell differentiation.},
	keywords = {Epithelial Cells, Epithelium, Corneal, Fucose, Humans, Mucins, Polysaccharides},
	issn = {2073-4409},
	doi = {10.3390/cells11091575},
	author = {Guindolet, Damien and Woodward, Ashley M and Gabison, Eric E and Arg{\"u}eso, Pablo}
}
@article {1773581,
	title = {The DeMixSC deconvolution framework uses single-cell sequencing plus a small benchmark dataset for improved analysis of cell-type ratios in complex tissue samples},
	journal = {bioRxiv},
	year = {2023},
	month = {2023 Oct 16},
	abstract = {We introduce a novel deconvolution framework, DeMixSC, to resolve technological discrepancies between bulk and single-cell/nucleus RNA-seq data, a critical issue unaddressed by existing single-cell-based deconvolution methods. Built upon the weighted non-negative least squares framework, DeMixSC introduces two key improvements: it leverages a small benchmark dataset to identify and rescale genes affected by technological discrepancies; it employs a novel weight function to account for variations across subjects and cells. The advanced utility of DeMixSC is demonstrated by its superior deconvolution accuracy on a benchmark dataset of healthy retinas and its broad applicability to a large aged-macular degeneration (AMD) cohort. Our work is the first to systematically evaluate the impact of technological discrepancies on deconvolution performance and underscores the importance of using a benchmark dataset to counteract these discrepancies. Our study positions DeMixSC as a transferable tool for accurate deconvolution of large bulk RNA-seq cohorts, necessitating only a tissue-type match between the benchmark and targeted datasets.},
	doi = {10.1101/2023.10.10.561733},
	author = {Guo, Shuai and Liu, Xiaoqian and Cheng, Xuesen and Jiang, Yujie and Ji, Shuangxi and Liang, Qingnan and Koval, Andrew and Li, Yumei and Owen, Leah A and Kim, Ivana K and Aparicio, Ana and Shen, John Paul and Kopetz, Scott and Weinstein, John N and Deangelis, Margaret M and Chen, Rui and Wang, Wenyi}
}
@article {1417559,
	title = {Intraocular pressure fluctuation and the risk of glaucomatous damage deterioration: a Meta-analysis},
	journal = {Int J Ophthalmol},
	volume = {12},
	number = {1},
	year = {2019},
	month = {2019},
	pages = {123-128},
	abstract = {AIM: To systematically review whether the increased fluctuation of intraocular pressure (IOP) is a risk factor for open angle glaucoma (OAG) progression. METHODS: Scientific studies relevant to IOP fluctuation and glaucoma progression were retrieved from MEDLINE, EMBASE and CENTRAL databases, and were listed as references in this paper. The hazard ratio (HR) was calculated by using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: Individual data for 2211 eyes of 2637 OAG patients in fourteen prospective studies were included in this Meta-analysis. All studies were longitudinal clinical studies with follow-up period ranging from 3 to 8.5y. The combined HR was 1.23 (95\%CI 1.04-1.46, =0.02) for the association between IOP fluctuation and glaucoma onset or progression with the evidence of heterogeneity (\&lt;0.1). Subgroup analyses with different types of IOP fluctuation were also evaluated. Results indicated that the summary HR was 0.98 (95\%CI 0.78-1.24) in short-term IOP fluctuation group, which showed no statistical significance with heterogeneity, whereas, the combined HR was 1.43 (95\%CI 1.13-1.82, =0.003) in long-term IOP fluctuation group without homogeneity. Sensitivity analysis further showed that the pooled HR was 1.10 (95\%CI 1.03-1.18, =0.004) for long-term IOP fluctuation and visual function progression with homogeneity among studies (=0.3). CONCLUSION: Long-term IOP fluctuation can be a risk factor for glaucoma progression based on the presented evidence. Thus, controlling the swing of IOP is crucial for glaucoma or glaucoma suspecting patients.},
	issn = {2222-3959},
	doi = {10.18240/ijo.2019.01.19},
	author = {Guo, Zhen-Zhen and Chang, Karen and Wei, Xin}
}
@article {1806491,
	title = {CB1R dysfunction of inhibitory synapses in the ACC drives chronic social isolation stress-induced social impairments in male mice},
	journal = {Neuron},
	volume = {112},
	number = {3},
	year = {2024},
	month = {2024 Feb 07},
	pages = {441-457.e6},
	abstract = {Social isolation is a risk factor for multiple mood disorders. Specifically, social isolation can remodel the brain, causing behavioral abnormalities, including sociability impairments. Here, we investigated social behavior impairment in mice following chronic social isolation stress (CSIS) and conducted a screening of susceptible brain regions using functional readouts. CSIS enhanced synaptic inhibition in the anterior cingulate cortex (ACC), particularly at inhibitory synapses of cholecystokinin (CCK)-expressing interneurons. This enhanced synaptic inhibition in the ACC was characterized by CSIS-induced loss of presynaptic cannabinoid type-1 receptors (CB1Rs), resulting in excessive axonal calcium influx. Activation of CCK-expressing interneurons or conditional knockdown of CB1R expression in CCK-expressing interneurons specifically reproduced social impairment. In contrast, optogenetic activation of CB1R or administration of CB1R agonists restored sociability in CSIS mice. These results suggest that the CB1R may be an effective therapeutic target for preventing CSIS-induced social impairments by restoring synaptic inhibition in the ACC.},
	keywords = {Animals, Cannabinoids, Gyrus Cinguli, Interneurons, Male, Mice, Receptor, Cannabinoid, CB1, Social Isolation, Synapses},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2023.10.027},
	author = {Guo, Baolin and Xi, Kaiwen and Mao, Honghui and Ren, Keke and Xiao, Haoxiang and Hartley, Nolan D and Zhang, Yangming and Kang, Junjun and Liu, Yingying and Xie, Yuqiao and Zhou, Yongsheng and Zhu, Yuanyuan and Zhang, Xia and Zhanyan Fu and Chen, Jiang-Fan and Hu, Hailan and Wang, Wenting and Wu, Shengxi}
}
@article {1323924,
	title = {Inhibition of Human Corneal Myofibroblast Formation},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {8},
	year = {2018},
	month = {2018 Jul 02},
	pages = {3511-3520},
	abstract = {Purpose: Transforming growth factor-beta (TGF-β) isoform 1 (T1) is involved in corneal fibrotic wound healing by stimulating myofibroblast transformation and altering fibrotic gene expression. In this study, two specific inhibitors were used to dissect the relationship between myofibroblast generation and the TGF-β/Smad- or TGF-β/p38-signaling pathway in human corneal fibroblasts (HCF). Methods: In HCF, Trx-SARA (Smad-pathway inhibitor) was used to block the TGF-β/Smad-signaling pathway, and the p38 inhibitor (p38inh, SB202190) was used to inhibit p38MAPK, thus blocking the TGF-β/p38-signaling pathway. HCF {\textpm} Trx-SARA or Trx-GA (SARA control) were serum starved overnight in Eagle{\textquoteright}s minimum essential medium (EMEM) {\textpm} p38inh, grown in EMEM {\textpm} T1 {\textpm} p38inh for 24 hours, and then processed for indirect-immunofluorescence, Western blot, or quantitative real-time polymerase chain reaction to examine α-smooth muscle actin (αSMA) and other fibrotic genes, such as fibronectin, thrombospondin1, and type III collagen. In addition, the morphology and the effect of p38inh on myofibroblast phenotype after myofibroblast formation were examined. Results: We observed that Trx-SARA had little effect on αSMA expression, indicating that blocking the Smad pathway did not significantly inhibit myofibroblast formation. However, p38inh did significantly inhibit αSMA and other fibrotic genes, thus efficiently preventing the transition of HCFs to myofibroblasts. In addition, morphology changed and αSMA decreased in myofibroblasts exposed to p38inh medium, as compared with controls. Conclusions: HCF transition to myofibroblasts was mainly through the p38 pathway. Therefore, blocking the p38 pathway may be a potential therapeutic tool for human corneal fibrosis prevention/treatment, because it controls myofibroblast formation in human corneal cells, while leaving other functions of T1 unaffected.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-24239},
	author = {Guo, Xiaoqing and Sriram, Sriniwas and Tran, Jennifer A and Hutcheon, Audrey E K and Zieske, James D}
}
@article {1667705,
	title = {Low Vision Rehabilitation Service Utilization Before and After Implementation of a Clinical Decision Support System in Ophthalmology},
	journal = {JAMA Netw Open},
	volume = {6},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {e2254006},
	abstract = {IMPORTANCE: Electronic clinical decision support systems apply clinical guidelines in real time and offer a new approach to improve referral and utilization of low vision rehabilitation (LVR) care. OBJECTIVE: To characterize patients and factors associated with LVR service utilization with and without the use of an electronic health record (EHR) clinical decision support system (CDSS) alert. DESIGN, SETTING, AND PARTICIPANTS: Quality improvement study using EHR data to compare patients who did and did not utilize LVR service after referral between November 6, 2017, and October 5, 2019, (primary) and to assess overall service utilization rate from September 1, 2016, to April 2, 2021, regardless of referral status (secondary). Participants in the primary analysis were patients at a large ophthalmology department in an academic medical center in the US who received an LVR referral recommendation from their ophthalmologist according to the CDSS alert. The secondary analysis included patients with best documented visual acuity (BDVA) worse than 20/40 before, during, and after the CDSS implementation. Data were analyzed from August 2021 to April 2022. EXPOSURES: Number and locations of referral recommendations for LVR service according to the CDSS alert in the primary analysis; active CDSS implementation in the secondary analysis. MAIN OUTCOMES AND MEASURES: LVR service utilization rate was defined as the number of patients who accessed service among those who were referred (primary) and among those with BDVA worse than 20/40 (secondary). EHR data on patient demographics (age, sex, race, ethnicity) and ophthalmology encounter characteristics (numbers of referral recommendations, encounter location, and BDVA) were extracted. RESULTS: Of the 429 patients (median [IQR] age, 71 [53 to 83] years; 233 female [54\%]) who received a CDSS-based referral recommendation, 184 (42.9\%) utilized LVR service. Compared with nonusers of LVR, users were more likely to have received at least 2 referral recommendations (12.5\% vs 6.1\%; χ21 = 5.29; P = .02) and at an ophthalmology location with onsite LVR service (87.5\% vs 78.0\%; χ21 = 6.50; P = .01). Onsite LVR service (odds ratio, 2.06; 95\% CI, 1.18-3.61) persisted as the only statistically significant factor after adjusting for patient demographics and other referral characteristics. Among patients whose BDVA was worse than 20/40 before, during, and after the CDSS implementation regardless of referral status, the LVR service utilization rate was 6.1\%, 13.8\%, and 7.5\%, respectively. CONCLUSIONS AND RELEVANCE: In this quality improvement study, ophthalmologist referral recommendations and onsite LVR services at the location where patients receive other ophthalmic care were significantly associated with service utilization. Ophthalmology CDSSs are promising tools to apply clinical guidelines in real time to improve connection to care.},
	keywords = {Academic Medical Centers, Aged, Decision Support Systems, Clinical, Electronic Health Records, Female, Humans, Ophthalmology, Vision, Low},
	issn = {2574-3805},
	doi = {10.1001/jamanetworkopen.2022.54006},
	author = {Guo, Xinxing and Boland, Michael V and Swenor, Bonnie K and Goldstein, Judith E}
}
@article {1623358,
	title = {Visual acuity and refractive findings in children prescribed glasses from a school-based vision program},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Nov 06},
	abstract = {PURPOSE: We report visual acuity improvement and refractive profiles in children prescribed glasses by a school-based vision program (SBVP) in Baltimore, Maryland. METHODS: In this cross-sectional analysis, pre-kindergarten through 8th grade students who failed vision screening underwent an eye examination. Students prescribed glasses are included. Visual acuity improvement was the difference between presenting and best-corrected visual acuity based on noncycloplegic manifest refraction. Clinically significant refractive error (CSRE) was defined as >=0.75 D myopia, >=2.00 D hyperopia without strabismus, >=1.00 D hyperopia with esodeviation, or >=1.50 D astigmatism AND presenting visual acuity <=20/40 or >=2-line difference with the better-seeing eye <=20/30. Characteristics associated with greater visual acuity improvement were explored. RESULTS: Of the 4,972 students, mean age was 9.4 {\textpm} 2.7 years; 77\% were black, and 18\% were Hispanic. Myopia, hyperopia, astigmatism, and CSRE were found in 65\%, 24\%, 60\%, and 46\% students, respectively. In the better-seeing eyes, 70\% gained >=2 lines. Of students with CSRE, improvement of at least 5 lines in the worse-seeing eye increased from 30.9\% in pre-kindergarten and kindergarten to 77.3\% in 7th and 8th grade (Ptrend \&lt; 0.001). Students with CSRE had a higher rate of gaining at least 2 lines{\textquoteright} improvement in their worse-seeing eyes compared with those without (98.7\% vs 80.6\%). Older students as well as blacks and Hispanics were more likely to have improvement of at least 2 lines. CONCLUSIONS: Most students prescribed glasses from our SBVP had clinically significant visual deficits corrected.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2021.07.013},
	author = {Guo, Xinxing and Friedman, David S and Repka, Michael X and Collins, Megan E}
}
@article {1309970,
	title = {Comparison of T Helper Cell Patterns in Primary Open-Angle Glaucoma and Normal-Pressure Glaucoma},
	journal = {Med Sci Monit},
	volume = {24},
	year = {2018},
	month = {2018 Apr 04},
	pages = {1988-1996},
	abstract = {BACKGROUND HSP60-related immunological activities are found in normal-pressure glaucoma (NPG) patients, in whom an elevated intraocular pressure (IOP) found in primary open-angle glaucoma (POAG) is not observed. HSP60 was found in POAG and NPG patients, while anti-HSP60 level was mainly found to be higher in NPG patients. The purpose of this study was to compare the percentages of Th cells and levels of related cytokines, attempting to provide evidence to explain this discrepancy. MATERIAL AND METHODS Blood samples from POAG, NPG, and normal control (NC) groups were collected and peripheral blood monocytes were isolated and cultured with or without the stimulation of HSP60. Flow cytometry and enzyme-linked immunosorbent assay were used to assess the percentages of Th1, Th2, Th17, and Treg cells, as well as HSP60 antibody levels and related cytokine levels, before and after culture. RESULTS Significantly higher titers of anti-HSP60 were observed only in NPG patients. Comparable Th1 and Th2 cell frequencies, IL-4 level, and IFN-γ level were found in POAG and NPG patients, while higher Treg cell frequency was only found in POAG patients. After culturing with HSP60, increased Th2 frequencies and decreased Th1 frequencies were observed in the POAG, NPG, and NC groups, while increased Treg frequency was only identified in the POAG and NC groups. CONCLUSIONS Different Th cell patterns were observed among POAG, NPG, and NC groups. Lack of induction of Treg cells and imbalance of the pro-inflammatory and anti-inflammatory response patterns of Th cells exist in some NPG patients.},
	issn = {1643-3750},
	author = {Guo, Chunyu and Wu, Ningbo and Niu, Xiaoyin and Wu, Yue and Chen, Dong Feng and Guo, Wenyi}
}
@article {1635633,
	title = {Noncycloplegic Compared with Cycloplegic Refraction in a Chicago School-Aged Population},
	journal = {Ophthalmology},
	volume = {129},
	number = {7},
	year = {2022},
	month = {2022 07},
	pages = {813-820},
	abstract = {PURPOSE: To evaluate differences between autorefraction measurements with and without cycloplegia among school-aged individuals and to explore factors associated with significant differences. DESIGN: Cross-sectional, retrospective study. PARTICIPANTS: Individuals between 3 and 22 years of age evaluated at the Illinois College of Optometry from September 2016 through June 2019 who underwent same-day noncycloplegic and cycloplegic autorefraction of the right eye. METHODS: Demographic information including age, sex, and race or ethnicity were collected during the eye examination. Autorefraction was performed before and after cycloplegia. Myopia, defined as at least -0.50 diopter (D) spherical equivalent (SE), hyperopia, defined as at least\&nbsp;+0.50 D SE, and astigmatism of at least 1.00 D cylinder were determined using noncycloplegic and cycloplegic autorefractions. Factors associated with at least 1.00 D more myopic SE or at least 0.75 D cylindrical difference by noncycloplegic autorefraction were assessed using logistic regression models. MAIN OUTCOME MEASURES: Differences between noncycloplegic and cycloplegic autorefraction measurements. RESULTS: The mean age was 10.8 {\textpm} 4.0 years for the 11 119 individuals; 52.4\% of participants were female. Noncycloplegic SE measured 0.65 {\textpm} 1.04 D more myopic than cycloplegic SE. After adjusting for demographic factors and refractive error, individuals with at least 1.00 D of more myopic SE refraction by noncycloplegic autorefraction (25.9\%) were more likely to be younger than 5 years (odds ratio [OR], 1.45; 95\% confidence interval [CI], 1.18-1.79) and 5 to younger than 10 years (OR, 1.32; 95\% CI, 1.18-1.48) than those 10 to younger than 15 years. This difference of at least 1.00 D of more myopic SE was more likely to be observed in Hispanic people (OR, 1.23; 95\% CI, 1.10-1.36) and those with hyperopia (OR range, 4.20-13.31). Individuals with 0.75 D or more of cylindrical difference (5.1\%) between refractions were more likely to be younger than 5 years, to be male, and to have mild-moderate-high myopia or moderate-high hyperopia. CONCLUSIONS: Three quarters of school-aged individuals had \&lt; 1 D of myopic SE difference using noncycloplegic compared with cycloplegic autorefraction. Understanding measurement differences obtained for refractive error and associated factors may provide useful information for future studies or programs involving refraction in school-aged children.},
	keywords = {Adolescent, Chicago, Child, Cross-Sectional Studies, Female, Humans, Hyperopia, Male, Mydriatics, Myopia, Presbyopia, Pupil Disorders, Refraction, Ocular, Refractive Errors, Retrospective Studies},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.02.027},
	author = {Guo, Xinxing and Shakarchi, Ahmed F and Block, Sandra S and Friedman, David S and Repka, Michael X and Collins, Megan E}
}
@article {1603848,
	title = {Refractive Error Findings in Students Who Failed School-based Vision Screening},
	journal = {Ophthalmic Epidemiol},
	year = {2021},
	month = {2021 Jul 22},
	pages = {1-9},
	abstract = {PURPOSE: To report refractive error findings in Baltimore City schoolchildren who failed school-based vision screenings. METHODS: In this cross-sectional analysis, students pre-kindergarten through 8th grade who failed screenings during school years 2016-2019 received an eye examination, including non-cycloplegic autorefraction and visual acuity (VA) measurements. Refractive error was identified when there was at least: -0.50 diopter (D) spherical equivalent (SE) myopia, +0.50D SE hyperopia, 1.00D astigmatism, or 1.00D anisometropia in either eye. Generalized estimating equation models were used to identify factors associated with clinically significant refractive error, defined as decreased VA and more severe refractive error. RESULTS: Of 7520 students who failed screening, 6627 (88\%) were analyzed. Clinically significant refractive error and any refractive error were found in 2352 (35.5\%) and 5952 (89.8\%) students, respectively. Mild myopia (45\%, -0.50 D to \&lt;-3.00 D SE) and low astigmatism (47\%, 1.00 D to \&lt;3.00 D cylinder) were the most prevalent types of refractive error. Proportions of students with myopia increased with higher grade levels (Ptrend\&lt;0.001). Myopia and astigmatism were more common in black and Latinx. Risk factors for clinically significant refractive error included higher grades (odds ratios [OR] ranged from 1.30 to 2.19 compared with 1st grade, P \&lt; .05) and Latinx ethnicity (OR = 1.31, 95\%CI: 1.08-1.59). CONCLUSION: A Baltimore school-based vision program identified a substantial number of students with refractive error in a high-poverty urban community. Over 1/3 students who failed vision screening had clinically significant refractive error, with black and Latinx students at higher risk of having myopia and astigmatism.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2021.1954664},
	author = {Guo, Xinxing and Nguyen, Angeline M and Vongsachang, Hursuong and Kretz, Alyssa M and Mukherjee, M Rani and Neitzel, Amanda J and Shakarchi, Ahmed F and Friedman, David S and Repka, Michael X and Collins, Megan E}
}
@article {1302192,
	title = {IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Feb 01},
	pages = {2054},
	abstract = {Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-20463-5},
	author = {Guo, Chenying and Cho, Kin-Sang and Li, Yingqian and Tchedre, Kissauo and Antolik, Christian and Ma, Jie and Chew, Justin and Utheim, Tor Paaske and Huang, Xizhong A and Yu, Honghua and Malik, Muhammad Taimur A and Anzak, Nada and Chen, Dong Feng}
}
@article {1661605,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {129},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {e157-e158},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.08.018},
	author = {Guo, Xinxing and Collins, Megan E and Block, Sandra S and Repka, Michael X and Friedman, David S}
}
@article {931071,
	title = {Varicella Zoster Virus Necrotizing Retinitis in Two Patients with Idiopathic CD4 Lymphocytopenia.},
	journal = {Ocul Immunol Inflamm},
	volume = {24},
	number = {5},
	year = {2016},
	month = {2016 Oct},
	pages = {544-8},
	abstract = {PURPOSE: Progressive outer retinal necrosis (PORN) associated with varicella zoster virus (VZV) is usually diagnosed in HIV positive or immunosuppressed patients. We report two cases of immunocompetent patients with necrotizing viral retinitis found to have idiopathic CD4 lymphocytopenia. METHODS: Clinical presentation, examination, imaging, and laboratory testing of two patients with VZV retinitis are presented. RESULTS: An HIV negative patient with history of herpes zoster presented with rapid loss of vision and examination consistent with PORN. PCR testing confirmed VZV. Lymphocytopenia was noted with a CD4 count of 25/mm(3). A second HIV negative patient presented with blurred vision and lid swelling and was found to have peripheral VZV retinitis confirmed by PCR. Laboratory workup revealed lymphocytopenia with a CD4 count of 133/mm(3). CONCLUSIONS: VZV necrotizing retinitis classic for PORN can occur in HIV negative patients. Idiopathic CD4 lymphocytopenia should be considered healthy patients who develop ocular infections seen in the immunocompromised.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2015.1034376},
	author = {Gupta, Meenakashi and Jardeleza, Maria Stephanie R and Kim, Ivana and Durand, Marlene L and Kim, Leo and Lobo, Ann-Marie}
}
@article {1154926,
	title = {Gene therapy for inherited retinal degenerations: initial successes and future challenges},
	journal = {J Neural Eng},
	volume = {14},
	number = {5},
	year = {2017},
	month = {2017 Oct},
	pages = {051002},
	abstract = {Inherited retinal degenerations are a clinically and genetically heterogeneous group of conditions that have historically shared an untreatable course. In recent years, however, a wide range of therapeutic strategies have demonstrated efficacy in preclinical studies and entered clinical trials with a common goal of improving visual function for patients affected with these conditions. Gene therapy offers a particularly elegant and precise opportunity to target the causative genetic mutations underlying these monogenic diseases. The present review will provide an overview of gene therapy with particular emphasis on key clinical results to date and challenges for the future.},
	issn = {1741-2552},
	doi = {10.1088/1741-2552/aa7a27},
	author = {Gupta, Priya R and Huckfeldt, Rachel M}
}
@article {439691,
	title = {Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {8},
	year = {2015},
	month = {2015 Aug 1},
	pages = {881-7},
	abstract = {IMPORTANCE: Somatic mutations in BAP1 (BRCA1-associated protein 1 gene) are frequently identified in uveal melanoma. To date, the role of germline BAP1 mutations in uveal melanoma has not been characterized. OBJECTIVE: To characterize the clinical phenotype of uveal melanoma in patients with germline BAP1 mutations. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at an academic ophthalmology referral center among 507 patients with uveal melanoma who consented for collection of blood samples. The study dates were June 22, 1992, to December 14, 2010. MAIN OUTCOMES AND MEASURES: Clinical characteristics of uveal melanoma and the development of metastases. BAP1 gene sequencing from blood samples of patients with uveal melanoma was correlated with clinical characteristics. RESULTS: Of 507 blood samples analyzed, 25 patients (4.9\%) exhibited 18 BAP1 polymorphisms, of which 9 were novel. Computational analyses predicted that 8 BAP1 mutations in 8 patients (1.6\%) were likely to result in damaged BAP1 protein. Five of these 8 mutations were novel. These 8 patients were compared with 482 patients in whom no BAP1 polymorphisms were identified. In univariate analyses, patients with germline BAP1 mutations exhibited larger tumor diameters (mean, 15.9 vs 12.3 mm; P = .004) and higher rates of ciliary body involvement (75.0\% vs 21.6\%, P = .002) and metastases (71.4\% vs 18.0\%, P = .003) compared with control subjects. Patients with germline BAP1 mutations exhibited increased frequency of family history of cancer (100\% vs 65.9\%, P = .06), particularly cutaneous melanoma (62.5\% vs 9.9\%, P \&lt; .001) and ocular melanoma (25.0\% vs 1.9\%, P = .01). No differences were identified in age at diagnosis, sex, history of other malignant neoplasm, presenting visual acuity, distance of the tumor from the optic nerve or fovea, iris involvement, extrascleral extension, or tumor pigmentation. Germline BAP1 mutations increased risk of metastasis independent of ciliary body involvement (P = .02). Germline BAP1 mutation approached significance as an independent risk factor for metastasis (P = .09). CONCLUSIONS AND RELEVANCE: These data suggest that germline BAP1 mutations occur infrequently in uveal melanoma and are associated with larger tumors and higher rates of ciliary body involvement, 2 known risk factors for metastasis.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.1119},
	author = {Gupta, Mrinali P and Lane, Anne Marie and Deangelis, Margaret M and Mayne, Katie and Crabtree, Margaux and Gragoudas, Evangelos S and Kim, Ivana K}
}
@article {1354341,
	title = {Intermittent Horner syndrome in a pediatric patient},
	journal = {J Neuroophthalmol},
	volume = {34},
	number = {2},
	year = {2014},
	month = {2014 Jun},
	pages = {149-50},
	abstract = {Intermittent Horner syndrome is uncommon in both the adult and pediatric population. We describe a case of a pediatric patient with an intermittent Horner syndrome. Infrared photography and videography were used to help establish the diagnosis.},
	keywords = {Adolescent, Brain, Horner Syndrome, Humans, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Male},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000062},
	author = {Gupta, Meenakashi and Leskov, Ilya and Kruger, Joshua M and Cestari, Dean M}
}
@article {1359929,
	title = {Effect of phase-plate adjustment on retinal image sharpness and visible retinal area on ultrawide field imaging},
	journal = {Eye (Lond)},
	volume = {33},
	number = {4},
	year = {2019},
	month = {2019 04},
	pages = {587-591},
	abstract = {BACKGROUND: To evaluate changes in image sharpness across ultrawide field (UWF) images and the effect of phase-plate adjustment on image contrast and extent of visible retinal area (VRA). METHODS: This was a single site evaluation of 200{\textdegree} UWF images acquired with phase-plate adjustment (California, Optos, plc) and without (200TX, Optos, plc). Images were acquired using standardized protocol. VRA was manually outlined on each image and quantified using customized software. Mean image sharpness was evaluated using an automated method within the full VRA of each image and within the peripheral region of the VRA. The VRA and image sharpness were evaluated and compared between the two devices. RESULTS: Twenty eyes of 10 healthy volunteers were evaluated. Devices with and without phase-plate adjustment produced a similar extent of VRA. Eye steering increased VRA in devices with and without phase-plate adjustment by 39.3\% and 34.3\%, respectively. Regardless of gaze direction, mean sharpness of the full VRA was reduced in peripheral area with or without phase-plate adjustment. Compared to images without phase-plate adjustment, use of phase-plate adjustment reduced the loss of peripheral image sharpness in all fields (-4.2 to -26.0\%; p \&lt; 0.001 all fields). The sharpness of the peripheral area for on-axis images was 61.5\% higher with phase-plate adjustment. CONCLUSIONS: The use of phase-plate adjustment does not alter the extent of VRA. However, for on-axis images the loss of sharpness in the periphery is 4.5-fold less with phase-plate adjustment, potentially reducing the need to steer images and improving lesion detection in these areas.},
	issn = {1476-5454},
	doi = {10.1038/s41433-018-0270-5},
	author = {Gupta, Aditi and El-Rami, Hala and Barham, Rasha and Fleming, Alan and van Hemert, Jano and Sun, Jennifer K and Silva, Paolo S and Aiello, Lloyd Paul}
}
@article {987961,
	title = {Retinal findings and a novel TINF2 mutation in Revesz syndrome: Clinical and molecular correlations with pediatric retinal vasculopathies.},
	journal = {Ophthalmic Genet},
	year = {2017},
	month = {2017 Jan 17},
	pages = {1-10},
	abstract = {BACKGROUND: Revesz syndrome is a telomere disorder in the dyskeratosis congenita (DKC) spectrum characterized by exudative retinopathy, bone marrow failure, neuroradiographic abnormalities, and integumentary findings. MATERIALS/METHODS: We report the ophthalmologic findings, documented by examinations under anesthesia with clinical photography and fluorescein angiography, as well as the systemic manifestations and genetic and molecular testing, in identical twins with Revesz syndrome, and compare and contrast these features to those of other pediatric retinal vasculopathies. RESULTS: Both twins exhibited widespread avascularity and anomalous vasculature of the retinal periphery, retinal telangiectasias, and exudation. One twin developed a combination exudative/tractional/rhegmatogenous retinal detachment, while the other exhibited a focal collection of buds of retinal neovascularization. Both twins developed bone marrow failure and were found to have cerebellar hypoplasia and widespread cerebral calcifications. Telomere testing in lymphocytes and granulocytes revealed telomere length less than the 1st percentile for age, and gene sequencing revealed a novel mutation in the TINF2 gene, resulting in the T284P TIN2 protein variant. CONCLUSIONS: We report ophthalmic findings in twins with Revesz syndrome due to a previously unreported mutation in TINF2 and propose that phenotypic and molecular overlaps between DKC spectrum disorders and pediatric retinal vasculopathies may reflect a shared pathophysiologic basis.},
	issn = {1744-5094},
	doi = {10.1080/13816810.2016.1275019},
	author = {Gupta, Mrinali P and Talcott, Katherine E and Kim, David Y and Agarwal, Suneet and Mukai, Shizuo}
}
@article {1789216,
	title = {Novel tactile bottle neck adaptor facilitates eye drop adherence in visually impaired patients},
	journal = {BMJ Open Ophthalmol},
	volume = {8},
	number = {1},
	year = {2023},
	month = {2023 Dec 28},
	abstract = {PURPOSE: To test the use of Ring-IT, a novel 3D tactile bottle neck adaptor in topical eye drop adherence in visually impaired patients.

METHODS: Bottle neck ring adaptors with either one, two or three protrusions with cube or sphere endings were designed. In phase 1, low vision was simulated in healthy subjects (n=20) with a 20/200 vision simulator; while in phase 2, visually impaired patients (n=26; 20/70 or worse) were recruited. Subjects were randomised to six combinations of varying protrusions and shapes on medication bottles and asked to identify these traits at different presentations. Responses and time to identify were recorded.

RESULTS: Phase 1: 98.3\% of subjects correctly identified the number of protrusions. Mean time to identify was 4.5{\textpm}6.1 s. Identification success for cube and sphere end pieces were 91.7\% and 73.3\%, with average time for identification of 9.9{\textpm}7.6 and 10.9{\textpm}9.0 s. In phase 2, 92.3\% of subjects correctly identified the number of protrusions. Mean time to identify was 6.0{\textpm}3.0 s. Identification success for cube and sphere end pieces were 78.2\% and 74.4\%; with average time for identification of 7.5{\textpm}4.8 and 8.5{\textpm}5.6 s, respectively.

CONCLUSIONS: Ring-IT was identified with accuracy and speed by both low vision simulated subjects, and by patients with true limited visual capabilities. These tactile bottle neck ring adaptors can be used as an assistive low vision aid device and may increase eye drop regimen adherence in visually impaired patients.},
	keywords = {Humans, Ophthalmic Solutions, Refraction, Ocular, Self-Help Devices, Vision, Low},
	issn = {2397-3269},
	doi = {10.1136/bmjophth-2023-001462},
	author = {Gupta, Praveena K and Ishihara, Rhys and Zhao, Zhenyang and Owji, Shahin and Anyama, Easy and Schmitz-Brown, Mary and Chacin, Aisen C and Iyer, Bhavani and Friedman, David and Ladki, Malik Said}
}
@article {931066,
	title = {Evidence for Telemedicine for Diabetic Retinal Disease.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	month = {2017},
	pages = {22-28},
	abstract = {According to current projections, the number of Americans with diabetes mellitus will increase from 27.8 million in 2007 to 60.7 million in 2030. With the increasing gap between demand for eye care and supply of ophthalmologists and optometrists, and the non-uniform distribution of eye care providers in US counties, barriers to eye examinations will likely increase. Telemedicine assessment of diabetic retinal disease through remote retinal imaging and diagnosis has the potential to meet these growing demands. To establish evidence for a telemedicine program as an effective modality for diabetic retinopathy (DR) assessment, the interpretation of teleretinal images should compare favorably with Early Treatment Diabetic Retinopathy Study film or digital photographs. We review the current evidence on the critical features and characteristics of ocular telehealth programs for DR in the following categories: image gradability, mydriasis, sensitivity and specificity, cost-effectiveness, long-term effectiveness, patient comfort and satisfaction, and improvement of patient related outcomes.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228403},
	author = {Gupta, Aditi and Cavallerano, Jerry and Sun, Jennifer K and Silva, Paolo S}
}
@article {1309958,
	title = {Ift172 conditional knock-out mice exhibit rapid retinal degeneration and protein trafficking defects},
	journal = {Hum Mol Genet},
	volume = {27},
	number = {11},
	year = {2018},
	month = {2018 Jun 01},
	pages = {2012-2024},
	abstract = {Intraflagellar transport (IFT) is a bidirectional transport process that occurs along primary cilia and specialized sensory cilia, such as photoreceptor outersegments. Genes coding for various IFT components are associated with ciliopathies. Mutations in IFT172 lead to diseases ranging from isolated retinal degeneration to severe syndromic ciliopathies. In this study, we created a mouse model of IFT172-associated retinal degeneration to investigate the ocular disease mechanism. We found that depletion of IFT172 in rod photoreceptors leads to a rapid degeneration of the retina, with severely reduced electroretinography (ERG) responses by 1 month and complete outer-nuclear layer (ONL) degeneration by 2 months. We investigated molecular mechanisms of degeneration and show that IFT172 protein reduction leads to mislocalization of specific photoreceptor outersegment (OS) proteins (RHO, RP1, IFT139), aberrant light-driven translocation of alpha transducin and altered localization of glioma-associated oncogene family member 1 (GLI1). This mouse model exhibits key features of the retinal phenotype observed in patients with IFT172-associated blindness and can be used for in vivo testing of ciliopathy therapies.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddy109},
	author = {Gupta, Priya R and Pendse, Nachiket and Greenwald, Scott H and Leon, Mihoko and Liu, Qin and Pierce, Eric A and Bujakowska, Kinga M}
}
@article {1363115,
	title = {Orbital follicular hyperplasia in common variable immune deficiency syndrome},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {6},
	year = {2013},
	month = {2013 Nov-Dec},
	pages = {e160-2},
	abstract = {Common variable immune deficiency (CVID) is characterized by reduced serum immune globulins and impaired or absent antibody responses. Patients become more susceptible to infections and to lymphoproliferation and granulomatous inflammation. Ophthalmic manifestations of CVID are rare. The authors describe a case of orbital follicular hyperplasia in a 15-year-old girl with CVID syndrome causing proptosis and exposure keratopathy.},
	keywords = {Adolescent, Exophthalmos, Face, Female, Humans, Hyperplasia, Immunologic Deficiency Syndromes, Orbit, Orbital Diseases},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e3182873c61},
	author = {Gupta, Meenakashi and Shah, Ankoor S and Vergilio, Jo-Anne and Chou, Janet and Elliott, Alexandra}
}
@article {1304381,
	title = {SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN COATS DISEASE},
	journal = {Retina},
	volume = {39},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {1177-1185},
	abstract = {PURPOSE: To evaluate microstructural retinal abnormalities on spectral domain optical coherence tomography (SD-OCT) imaging of eyes with Coats disease. METHODS: This is a multicenter, retrospective study in which SD-OCT images of patients with treatment-naive Coats disease were correlated with clinical examination and visual acuity and, when available, followed longitudinally over time. RESULTS: Macular SD-OCT of 27 eyes with Coats disease revealed intraretinal edema (59\%), intraretinal exudates (67\%), subretinal fluid (37\%), subretinal exudate (48\%), ellipsoid zone disruption (52\%), external limiting membrane disruption (41\%), and subfoveal nodule (26\%). All these microstructural abnormalities correlated with worse baseline and final visual acuities (P \&lt; 0.05) on univariate analysis, except for intraretinal edema which exhibited a nonstatistically significant trend toward worse baseline visual acuity (P = 0.16). Within stage 2b eyes, external limiting membrane disruption and subretinal nodule on SD-OCT were associated with worse baseline visual acuity (P = 0.02 for both), and there was a trend toward worse final visual acuity with external limiting membrane disruption and subretinal nodule (P = 0.17 for both) and worse baseline (P = 0.08) and final (P = 0.13) visual acuities with ellipsoid zone disruption. No microstructural abnormalities were noted on OCT of fellow eyes. CONCLUSION: Spectral domain OCT can identify microstructural abnormalities in Coats disease that are associated on univariate analysis with worse baseline visual acuity and visual prognosis. Further larger studies are necessary.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002120},
	author = {Gupta, Mrinali P and Dow, Eliot and Jeng-Miller, Karen W and Mukai, Shizuo and Orlin, Anton and Xu, Kunyong and Yonekawa, Yoshihiro and Chan, R V Paul}
}
@article {1593827,
	title = {The role of KPI-121 0.25\% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares},
	journal = {Ther Adv Ophthalmol},
	volume = {13},
	year = {2021},
	month = {2021 Jan-Dec},
	pages = {25158414211012797},
	abstract = {The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film{\textquoteright}s ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25\% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25\%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients.},
	issn = {2515-8414},
	doi = {10.1177/25158414211012797},
	author = {Gupta, Preeya K and Venkateswaran, Nandini}
}
@article {1817266,
	title = {-associated non-syndromic optic neuropathy and rod-cone dystrophy},
	journal = {Ophthalmic Genet},
	year = {2024},
	month = {2024 Jan 15},
	pages = {1-5},
	abstract = {BACKGROUND: Biallelic variants in RTN4IP1 are a well-established cause of syndromic and nonsyndromic early-onset autosomal recessive optic neuropathy. They have more recently been reported to cause a concomitant but later-onset rod-cone dystrophy with or without syndromic features.

METHODS: A comprehensive evaluation was performed that included assessment of visual and retinal function, clinical examination, and retinal imaging. Childhood ophthalmic records as well as the results of genetic testing were evaluated.

RESULTS: A 24-year-old female described longstanding reduced visual acuity with more recent subjective impairment of dark adaptation. Visual acuity was subnormal in both eyes. Goldmann kinetic perimetry demonstrated scotomas in a pattern consistent with the presence of both optic neuropathy and rod-cone dystrophy with fundus exam as well as retinal imaging showing corroborating findings. Full-field electroretinography further confirmed the presence of a rod-cone dystrophy. Genetic testing demonstrated biallelic variants in RTN4IP1, one of which was novel, in association with the ocular findings.

CONCLUSIONS: RTN4IP1-associated early-onset bilateral optic neuropathy with rod-cone dystrophy is a recently described clinical entity with limited reports available to-date. The present case provides additional support for this dual phenotype and identifies a novel causative variant.},
	issn = {1744-5094},
	doi = {10.1080/13816810.2024.2303683},
	author = {Gupta, Priya R and O{\textquoteright}Connell, Kaitlin and Sullivan, Jack M and Huckfeldt, Rachel M}
}
@article {1698266,
	title = {Artificial intelligence in glaucoma: posterior segment optical coherence tomography},
	journal = {Curr Opin Ophthalmol},
	volume = {34},
	number = {3},
	year = {2023},
	month = {2023 May 01},
	pages = {245-254},
	abstract = {PURPOSE OF REVIEW: To summarize the recent literature on deep learning (DL) model applications in glaucoma detection and surveillance using posterior segment optical coherence tomography (OCT) imaging. RECENT FINDINGS: DL models use OCT derived parameters including retinal nerve fiber layer (RNFL) scans, macular scans, and optic nerve head (ONH) scans, as well as a combination of these parameters, to achieve high diagnostic accuracy in detecting glaucomatous optic neuropathy (GON). Although RNFL segmentation is the most widely used OCT parameter for glaucoma detection by ophthalmologists, newer DL models most commonly use a combination of parameters, which provide a more comprehensive approach. Compared to DL models for diagnosing glaucoma, DL models predicting glaucoma progression are less commonly studied but have also been developed. SUMMARY: DL models offer time-efficient, objective, and potential options in the management of glaucoma. Although artificial intelligence models have already been commercially accepted as diagnostic tools for other ophthalmic diseases, there is no commercially approved DL tool for the diagnosis of glaucoma, most likely in part due to the lack of a universal definition of glaucoma defined by OCT derived parameters alone (see Supplemental Digital Content 1 for video abstract, http://links.lww.com/COOP/A54 ).},
	keywords = {Artificial Intelligence, Glaucoma, Humans, Intraocular Pressure, Nerve Fibers, Retinal Ganglion Cells, Tomography, Optical Coherence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000934},
	author = {Gutierrez, Alfredo and Chen, Teresa C}
}
@article {1653602,
	title = {Two pediatric cases of reticular corneal epithelial edema associated with netarsudil},
	journal = {Am J Ophthalmol Case Rep},
	volume = {27},
	year = {2022},
	month = {2022 Sep},
	pages = {101638},
	abstract = {Purpose: To report two pediatric cases of reticular corneal epithelial edema associated with the use of netarsudil ophthalmic solution 0.02\%. Observations: In Case 1, a six-year-old male with glaucoma following cataract surgery was treated with netarsudil for thirteen months and developed diffuse reticular corneal epithelial edema on post-operative day one after undergoing transscleral diode cyclophotocoagulation for persistently elevated intraocular pressures. In Case 2, a three-month-old male with bilateral ocular hypertension developed unilateral inferior reticular corneal epithelial edema five weeks after initiation of netarsudil, which had been discontinued in the fellow eye two weeks prior. In both cases, the reticular epithelial edema resolved following cessation of netarsudil. Conclusions and Importance: Netarsudil-associated reticular corneal epithelial edema can occur in infants and young children.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101638},
	author = {Guzman Aparicio, Maria A and Liebman, Daniel L and Chodosh, James and Freitag, Suzanne K and Kazlas, Melanie and Mai, Derek D and Marando, Catherine M and Mukai, Shizuo and Wu, Annie M and Chen, Teresa C}
}
@article {1626103,
	title = {New views on three-dimensional imaging technologies for glaucoma: an overview},
	journal = {Curr Opin Ophthalmol},
	volume = {33},
	number = {2},
	year = {2022},
	month = {2022 Mar 01},
	pages = {103-111},
	abstract = {PURPOSE OF REVIEW: To summarize the literature on three-dimensional (3D) technological advances in ophthalmology, the quantitative methods associated with this, and their improved ability to help detect glaucoma disease progression. RECENT FINDINGS: Improvements in measuring glaucomatous structural changes are the result of dual innovations in optical coherence tomography (OCT) imaging technology and in associated quantitative software. SUMMARY: Compared with two-dimensional (2D) OCT parameters, newer 3D parameters provide more data and fewer artifacts.},
	keywords = {Glaucoma, Humans, Imaging, Three-Dimensional, Ophthalmology, Technology, Tomography, Optical Coherence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000828},
	author = {Guzman Aparicio, Maria A and Chen, Teresa C}
}
@article {1642389,
	title = {Cost Analysis: Port Delivery System vs Monthly Ranibizumab for wet AMD Treatment},
	journal = {Ophthalmol Retina},
	year = {2022},
	author = {Al-Kersan H and Patel NA and Yannuzzi NA and Lin J and Smiddy WE}
}
@article {1603844,
	title = {Medical comorbidities and orbital implant exposure},
	journal = {Acta Ophthalmol},
	volume = {100},
	number = {3},
	year = {2022},
	month = {2022 May},
	pages = {e813-e819},
	abstract = {PURPOSE: To investigate medical conditions and systemic therapies associated with orbital implant exposure in patients with anophthalmic sockets. METHODS: Retrospective review of patients who underwent enucleation or evisceration at a single centre between January 1, 2008 and March 1, 2018. Medical comorbidities, including peripheral or coronary artery disease, rheumatologic conditions, diabetes, malignancy and history of smoking were recorded. Use of immunomodulatory and anticoagulation therapy at the time of eye removal was noted. Patients were divided into two groups-those with implant exposure and those without. Univariate and multivariate analysis was used to compare groups. RESULTS: Two hundred and twenty-nine patients underwent eye removal surgery over a ten-year period. Implant exposure was seen in 20 (8.7\%) patients. Univariate analysis revealed a statistically significant difference between groups in rates of smoking, malignancy, and immunomodulatory therapy at the time of surgery. A history of smoking (HR = 11.72; 95\% CI: 2.95, 46.53; p = 0.0001) and immunomodulatory therapy (HR = 8.02; 95\% CI: 1.96, 32.87; p = 0.004) were independent predictors of exposure. The probability of exposure was 81.2\% when all three risk factors were present versus 4.4\% when none were present (c-index = 0.737, 95\% CI: 0.608, 0.865; p \&lt; 0.001). The model was a good fit to the data (Hosmer-Lemeshow goodness-of-fit test p = 0.475). CONCLUSIONS: Smoking and immunomodulatory therapy were associated with orbital implant exposure in patients with anophthalmic sockets. This is the first report examining medical comorbidities in patients with orbital implant exposure. Understanding the pathophysiology of implant exposure is crucial to preoperative planning and postoperative care.},
	keywords = {Anophthalmos, Eye Enucleation, Eye Evisceration, Humans, Orbital Implants, Postoperative Complications, Prosthesis Implantation, Retrospective Studies},
	issn = {1755-3768},
	doi = {10.1111/aos.14973},
	author = {Habib, Larissa A and North, Victoria S and Freitag, Suzanne K and Yoon, Michael K and Lefebvre, Daniel R and Lee, Nahyoung Grace}
}
@article {1445338,
	title = {Advances in Immunotherapy and Periocular Malignancy},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 09},
	pages = {1-7},
	abstract = {Immunotherapy has significantly advanced the field of oncology in recent decades. Understanding normal immunosurveillance, as well as the ways in which tumor cells have evolved to evade it, has provided the knowledge for development of drugs that allow one{\textquoteright}s own immune system to target and destroy malignant cells (immunotherapy). Cutaneous malignancies are particularly sensitive to this class of drugs. In a very sensitive anatomic region such as the periocular tissue, where surgical excision may come with significant morbidity, this technology has had a strong impact in the successful treatment of historically challenging tumors.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620813},
	author = {Habib, Larissa A and Wolkow, Natalie and Freitag, Suzanne K and Yoon, Michael K}
}
@article {1498247,
	title = {Pyoderma gangrenosum of the eyelid associated with inflammatory bowel disease},
	journal = {Am J Ophthalmol Case Rep},
	volume = {18},
	year = {2020},
	month = {2020 Jun},
	pages = {100623},
	abstract = {Purpose: Pyoderma gangrenosum (PG) of the eyelid can be difficult to diagnosis and may mimic other, more common pathologies, thereby delaying proper treatment and management. PG may be associated with systemic disorders that have significant comorbidities. Observations: The authors present two cases of pyoderma gangrenosum of the eyelid associated with inflammatory bowel disease. Conclusions and importance: This case series highlights the importance of early recognition of eyelid pyoderma gangrenosum to avoid local and systemic comorbidities with timely and appropriate management.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2020.100623},
	author = {Habib, Larissa A and Wolkow, Natalie and Cohen, Liza and Ma, Lina and Yoon, Michael K and Lee, Nahyoung Grace}
}
@article {1626110,
	title = {Patient specific implants in orbital reconstruction: A pilot study},
	journal = {Am J Ophthalmol Case Rep},
	volume = {24},
	year = {2021},
	month = {2021 Dec},
	pages = {101222},
	abstract = {Purpose: Successful repair of the orbital skeleton restores function and cosmesis by normalizing globe position and allowing full motility of the extraocular muscles. Routine repairs are successful with standard implants. However, defects that are irregular or cause volume deficiency can be challenging to repair. The development of patient specific implants (PSI) offers an additional tool in complex cases. Herein, we report our experience using PSI for orbital reconstruction. Methods: An IRB-approved review was conducted of consecutive patients who received PSI from 8/2016-9/2018. Demographic and examination findings were recorded. PSI was designed using high-density porous polyethylene or polyetheretherketone (PEEK) and implanted for repair. The postoperative course was reviewed for outcomes and complications. Results: Eight patients were identified. Two had silent sinus syndrome, 3 were complex facial fracture revisions, and 3 were post-oncologic reconstruction. Seven received porous polyethylene implants, and 1 had a PEEK implant. Mean follow up time was 10.2 months (3.3-28.3). All had an improved functional and aesthetic result. Diplopia and enophthalmos completely resolved in 60\% of fracture and silent sinus patients. All fracture and silent sinus patients were orthotropic without diplopia in primary gaze at last follow up. Tumor patients had improvement in symmetry and functionality. There were no complications. Conclusion and importance: Complex orbital skeleton derangements can be difficult to repair and standard implants may incompletely resolve the anatomic problem. In challenging cases, PSI may better achieve an aesthetically and anatomically successful outcome and improve functionality.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2021.101222},
	author = {Habib, Larissa A and Yoon, Michael K}
}
@article {1364609,
	title = {Thrombospondin-1 (TSP1)-null and TSP2-null mice exhibit lower intraocular pressures},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {10},
	year = {2012},
	month = {2012 Sep 28},
	pages = {6708-17},
	abstract = {PURPOSE: Thrombospondin-1 (TSP1) and TSP2 are matricellular proteins that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling. Both TSP1 and TSP2 are found in the trabecular meshwork (TM). In cadaver eyes with primary open-angle glaucoma (POAG), TSP1 is increased in one third of patients. We hypothesized that TSP1 and TSP2 participate in the regulation of intraocular pressure (IOP). Methods. IOPs of TSP1-null, TSP2-null mice, and their corresponding wild-type (WT) mice were measured using a commercial rebound tonometer. Fluorophotometric measurements assessed aqueous turnover. Central corneal thickness (CCT) was measured by optical coherence tomography. Iridocorneal angles were examined using light microscopy (LM), immunofluorescence (IF), and transmission electron microscopy (TEM). RESULTS: Average IOPs of TSP1-null and TSP2-null mice were 10\% and 7\% less than that of the corresponding WT mice, respectively. CCTs were 6.5\% less in TSP1-null mice (P \&lt; 0.05) and 1.1\% less in TSP2-null mice (P \&gt; 0.05). Fluorophotometric measurements suggest that aqueous turnover rates in TSP1-null and TSP2-null mice are greater than those of WT mice. LM of the TSP1-null and TSP2-null iridocorneal angles reveals morphology, which is indistinguishable from that of their corresponding WTs. IF revealed possible concurrent underexpression of TSP2 in TSP1-null mice and of TSP1 in TSP2-null mice. TEM revealed larger collagen fibril diameters in TSP1-null and TSP2-null mice compared with WTs. CONCLUSIONS: TSP1-null and TSP2-null mice have lower IOPs than their WT counterparts. The rate of aqueous turnover suggests that the mechanism is enhanced outflow facility. An alteration in the extracellular matrix may contribute to this finding.},
	keywords = {Animals, Aqueous Humor, Cell Adhesion, Cell Adhesion Molecules, Disease Models, Animal, Endothelium, Corneal, Extracellular Matrix, Fluorophotometry, Gene Expression Regulation, Glaucoma, Open-Angle, Immunoblotting, Intraocular Pressure, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Reverse Transcriptase Polymerase Chain Reaction, RNA, Thrombospondin 1, Thrombospondins, Tomography, Optical Coherence, Trabecular Meshwork},
	issn = {1552-5783},
	doi = {10.1167/iovs.11-9013},
	author = {Haddadin, Ramez I and Oh, Dong-Jin and Kang, Min Hyung and Villarreal, Guadalupe and Kang, Ja-heon and Jin, Rui and Gong, Haiyan and Rhee, Douglas J}
}
@article {1363116,
	title = {Simple, inexpensive technique for high-quality smartphone fundus photography in human and animal eyes},
	journal = {J Ophthalmol},
	volume = {2013},
	year = {2013},
	month = {2013},
	pages = {518479},
	abstract = {Purpose. We describe in detail a relatively simple technique of fundus photography in human and rabbit eyes using a smartphone, an inexpensive app for the smartphone, and instruments that are readily available in an ophthalmic practice. Methods. Fundus images were captured with a smartphone and a 20D lens with or without a Koeppe lens. By using the coaxial light source of the phone, this system works as an indirect ophthalmoscope that creates a digital image of the fundus. The application whose software allows for independent control of focus, exposure, and light intensity during video filming was used. With this app, we recorded high-definition videos of the fundus and subsequently extracted high-quality, still images from the video clip. Results. The described technique of smartphone fundus photography was able to capture excellent high-quality fundus images in both children under anesthesia and in awake adults. Excellent images were acquired with the 20D lens alone in the clinic, and the addition of the Koeppe lens in the operating room resulted in the best quality images. Successful photodocumentation of rabbit fundus was achieved in control and experimental eyes. Conclusion. The currently described system was able to take consistently high-quality fundus photographs in patients and in animals using readily available instruments that are portable with simple power sources. It is relatively simple to master, is relatively inexpensive, and can take advantage of the expanding mobile-telephone networks for telemedicine.},
	issn = {2090-004X},
	doi = {10.1155/2013/518479},
	author = {Haddock, Luis J and Kim, David Y and Mukai, Shizuo}
}
@article {931076,
	title = {CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING},
	journal = {Retina},
	volume = {37},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {417-423},
	abstract = {PURPOSE: Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. METHODS: A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. RESULTS: Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51\% to 57\%. These new sequencing tools are highly accurate with sensitivities of 97.9\% and specificities of 100\%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. CONCLUSION: Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001341},
	author = {Hafler, Brian P}
}
@article {1363117,
	title = {Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT)},
	journal = {Ophthalmology},
	volume = {120},
	number = {3},
	year = {2013},
	month = {2013 Mar},
	pages = {593-599},
	abstract = {PURPOSE: To evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD. DESIGN: Clinical trial. PARTICIPANTS: Eight hundred thirty-four (73\%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. METHODS: Each patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). MAIN OUTCOMES MEASURES: Genotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, P<=0.01 was considered statistically significant. RESULTS: No statistically significant differences in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing. CONCLUSIONS: Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy.},
	keywords = {Aged, Aged, 80 and over, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Bevacizumab, Complement C3, Complement Factor H, Female, Fluorescein Angiography, Gene Frequency, Genotype, High-Temperature Requirement A Serine Peptidase 1, Humans, Macular Degeneration, Male, Pharmacogenetics, Polymorphism, Single Nucleotide, Prospective Studies, Proteins, Ranibizumab, Serine Endopeptidases, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Visual Acuity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2012.11.037},
	author = {Hagstrom, Stephanie A and Ying, Gui-Shuang and Pauer, Gayle J T and Sturgill-Short, Gwen M and Huang, Jiayan and Callanan, David G and Kim, Ivana K and Klein, Michael L and Maguire, Maureen G and Martin, Daniel F and Comparison of AMD Treatments Trials Research Group}
}
@article {1532338,
	title = {Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study},
	journal = {Ophthalmology},
	volume = {128},
	number = {4},
	year = {2021},
	month = {2021 Apr},
	pages = {554-560},
	abstract = {PURPOSE: To determine the relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial. PARTICIPANTS: Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. METHODS: Stage of DR was measured every 6 months from standard fundus photographs, and refractive error was measured annually during the 6.5 years of DCCT; then, both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. Outcomes of DR were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME), or ocular surgery. Myopia, emmetropia, and hyperopia were defined as a spherical equivalent of <=-0.5, \&gt;-0.5 and \&lt;0.5, and >=0.5, respectively. MAIN OUTCOME MEASURES: For each outcome separately, Cox proportional hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95\% confidence interval [CI], 1.05-1.59), 3-step progression (HR, 1.35; 95\% CI, 1.05-1.73), and PDR (HR, 1.40; 95\% CI, 1.02-1.92) compared with emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (HbA1c) (2-step progression: HR, 1.28; 95\% CI, 1.03-1.58; 3-step progression: HR, 1.30; 95\% CI, 1.00-1.68; PDR: HR, 1.38; 95\% CI, 1.00-1.90). Myopia was not associated with any of the 5 DR outcomes in the unadjusted models and only marginally associated with 2-step progression (HR, 1.11; 95\% CI, 1.00-1.24) in the adjusted models. CONCLUSIONS: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.09.014},
	author = {Hainsworth, Dean P and Gao, Xiaoyu and Bebu, Ionut and Das, Arup and Olmos de Koo, Lisa and Barkmeier, Andrew J and Tamborlane, William and Lachin, John M and Aiello, Lloyd Paul and Diabetes Control and Complications Trial and Follow-up Epidemiology of Diabetes Interventions and Complications Research Group}
}
@article {1658651,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {129},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {e155-e156},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.07.020},
	author = {Halawa, Omar A and Kolli, Ajay and Oh, Gahee and Mitchell, William G and Glynn, Robert J and Kim, Dae Hyun and Friedman, David S and Zebardast, Nazlee}
}
@article {1619421,
	title = {Racial and Socioeconomic Differences in Eye Care Utilization among Medicare Beneficiaries with Glaucoma},
	journal = {Ophthalmology},
	volume = {129},
	number = {4},
	year = {2022},
	month = {2022 Apr},
	pages = {397-405},
	abstract = {PURPOSE: Evaluate differences in eye care utilization among patients with glaucoma by race and socioeconomic status (SES). DESIGN: Retrospective cohort study. PARTICIPANTS: Representative 5\% sample of Medicare beneficiaries aged \&gt; 65 years with continuous part A/B enrollment between January 1, 2014, and July 1, 2014, at least 1 diagnosis code for glaucoma within that period, and a glaucoma diagnosis in the Chronic Conditions Warehouse before January 1,\&nbsp;2014. METHODS: The following race/ethnicity categories were defined in our cohort: non-Hispanic White, Black/African American, Hispanic, and Asian/Pacific Islander. Low SES was defined as having 2 or more enrollment-based low-income indicators (dual eligibility for Medicare/Medicaid, Part D limited income subsidies, and eligibility for Part A and B State buy-in). Negative binomial regression analyses were carried out to compare relative rate ratios (RRs) of eye care utilization among racial groups stratified by low and non-low SES. MAIN OUTCOME MEASURES: Measured from July 1, 2014, to December 31, 2016: eye examinations and eye care-related office visits; eye care-related inpatient and emergency department (ED) encounters; eye care-related nursing home and home-visit encounters; visual field and retinal nerve fiber OCT tests; glaucoma lasers and surgeries. RESULTS: Among 78 526 participants with glaucoma, mean age was 79.1 years (standard deviation, 7.9 years), 60.9\% were female, 78.4\% were non-Hispanic White, and 13.8\% met enrollment-based criteria for low-SES. Compared with White beneficiaries, Blacks had lower counts of outpatient visits (RR, 0.92; 95\% confidence interval [CI], 0.90-0.93), visual field (VF) tests (RR, 0.92; 95\% CI, 0.90-0.94), but more inpatient/ED encounters (RR, 2.42; 95\% CI, 1.55-3.78) and surgeries (RR, 1.14; 95\% CI, 1.03-1.27). Hispanics had fewer outpatient visits (RR, 0.97; 95\% CI, 0.95-0.98) and retinal nerve fiber layer (RNFL) OCT tests (RR, 0.89; 95\% CI, 0.86-0.93), but more inpatient/ED encounters (RR, 2.32; 95\% CI, 1.18-4.57) and selective laser trabeculoplasty (SLT) (RR, 1.25; 95\% CI, 1.11-1.42) versus non-Hispanic Whites. In the non-low SES group, Black versus White disparities persisted in outpatient visits (RR, 0.93; 95\% CI, 0.92-0.95), VF (RR, 0.96; 95\% CI, 0.94-0.98), RNFL OCT (RR, 0.81; 95\% CI, 0.78-0.83), and inpatient/ED encounters (RR, 2.57; 95\% CI, 1.55-4.26). CONCLUSIONS: Disparities were found in eye care utilization among Black and Hispanic patients with glaucoma. These differences persisted among Blacks after stratification by SES, suggesting that systemic racism may be an independent driver in this population.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.09.022},
	author = {Halawa, Omar A and Kolli, Ajay and Oh, Gahee and Mitchell, William G and Glynn, Robert J and Kim, Dae Hyun and Friedman, David S and Zebardast, Nazlee}
}
@article {1589749,
	title = {Fall-related eye injury among older adults in the United States},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 Apr 10},
	abstract = {PURPOSE: To identify common causes of emergency department-treated eye injury among older adults in the United States (US), and to characterize of fall-related ocular trauma in this population. DESIGN: Retrospective cohort study METHODS: Data from the National Electronic Injury Surveillance System, a nationally representative database of US emergency department-treated injuries, was used to assemble a cohort of adults 65 years and older with eye injuries between January 1, 2000 and December 31, 2019. Demographic information, diagnosis, disposition, injury location and consumer product associated with injury were collected. Narrative descriptions of all injuries were reviewed to identify eye injuries secondary to falls. RESULTS: 4,953 eye injuries among older adults were reported from 2000 to 2019, a stratified probability sample representing approximately 238,162 injuries, with an average annual frequency of 12,000 injuries. Falls accounted for 11.5\% of these injuries. Fall-related eye injuries commonly presented from home (66.5\%) and were more likely to occur in the winter than eye injuries from other causes (28.1\% vs. 18.4\%, p\&lt;0.01). Risk factors for fall-related eye injury included older age (Odds ratio [OR] 1.11, 95\% confidence intervals [CI] 1.10-1.13 per year), female sex (OR 2.3, 95\% CI 1.6-3.1 vs. male), Black race (OR 2.4, 95\% CI 1.3-4.5 vs. White) and presentation from a nursing home (OR 12.7, 95\% CI 4.9-32.8 vs. other locations). Older adults with fall-related injury were more likely to be hospitalized (OR 22.8, 95\% CI 15.3-33.9) and to suffer from a ruptured globe (OR 14.1, 95\% CI 6.5-30.6) than those with fall-unrelated injury. CONCLUSIONS: Falls are an important mechanism of ocular trauma in older adults and are associated with worse outcomes compared to eye injuries from other causes.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.03.063},
	author = {Halawa, Omar and Mitchell, William and Zebardast, Nazlee}
}
@article {1642020,
	title = {Sex-Based Differences in Medicare Reimbursements among Ophthalmologists Persist across Time},
	journal = {Ophthalmology},
	volume = {129},
	number = {9},
	year = {2022},
	month = {2022 09},
	pages = {1056-1063},
	abstract = {PURPOSE: To evaluate differences in Medicare reimbursements between male and female ophthalmologists between 2013 and\&nbsp;2019. DESIGN: Retrospective cohort study. PARTICIPANTS: Ophthalmologists receiving Medicare reimbursements between 2013 and\&nbsp;2019. METHODS: The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to determine total reimbursements and number of services submitted by ophthalmologists between 2013 and 2019. Reimbursements were standardized to account for geographic differences in Medicare reimbursement per service. Data from the American Community Survey (ACS) were used to determine socioeconomic characteristics (unemployment, poverty, income, and education) by zip code for the location of each physician{\textquoteright}s practice. A multivariate linear regression model was used to evaluate differences in annual reimbursements by sex, accounting for calendar year, years of experience, total number of services, ACS zip code data, and proportion of procedural services. MAIN OUTCOME MEASURES: Annual Medicare reimbursement and use of billing codes (e.g., outpatient office visits and eye examinations, diagnostic testing, laser treatment, and surgery). RESULTS: Among 20 281 ophthalmologists who received Medicare reimbursements between 2013 and 2019, 15 451 (76\%) were men. The most common billing codes submitted were for outpatient visits and eye examinations (13.8 million charges/year), diagnostic imaging of the retina (5.6 million charges/year), intravitreal injections (2.9 million charges/year), and removal of cataract with insertion of lens (2.4 million charges/year). Compared with men, female ophthalmologists received less in median annual reimbursements (median, $94 734.21 [interquartile range (IQR), $30 944.52-$195 701.70] for women vs. $194 176.90 [IQR, $76 380.76-$355 790.80] for men; P \&lt; 0.001) and billed for fewer annual median services (median, 1228 [IQR, 454-2433] vs. 2259 [IQR, 996-4075, respectively]; P \&lt; 0.001). After adjustment for covariates, female ophthalmologists billed for 1015 fewer services (95\% confidence interval [CI], 1001-1029; P \&lt; 0.001) and received $20 209.12 less in reimbursements than men (95\% CI, -$21 717.57 to -$18 700.66; P \&lt; 0.001). CONCLUSIONS: Female ophthalmologists billed for fewer services and received less in reimbursement from Medicare than men over time and across all categories of billing codes. Disparities persisted after controlling for physician and practice characteristics.},
	keywords = {Aged, Centers for Medicare and Medicaid Services, U.S., Female, Humans, Intravitreal Injections, Male, Medicare, Ophthalmologists, Retrospective Studies, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.05.006},
	author = {Halawa, Omar Alaa and Sekimitsu, Sayuri and Boland, Michael V and Zebardast, Nazlee}
}
@article {1655716,
	title = {Race and Ethnicity Differences in Disease Severity and Visual Field Progression Among Glaucoma Patients},
	journal = {Am J Ophthalmol},
	volume = {242},
	year = {2022},
	month = {2022 Oct},
	pages = {69-76},
	abstract = {PURPOSE: Investigate associations of race/ethnicity and preferred language with baseline glaucoma severity, VF test frequency and disease progression. DESIGN: Retrospective cohort study. METHODS: Patients receiving VF testing at a tertiary eyecare center between 1998 and 2020 with self-identified race, ethnicity and preferred language were included. Outcome measures were VF MD and age at first visit, VF test frequency, VF MD progression. RESULTS: Among 29,891 patients with VF measurements between 1998 and 2020, 55.1\% were female, 71.0\% self-identified as White/Caucasian, 14.0\% as Black/African American, 7.4\% as Asian and 6.4\% as Hispanic, and 11.2\% preferred a language other than English. Mean VF MD at presentation was worse among Black (-9.3{\textpm}9.7 dB), Asian (-6.2{\textpm}7.6 dB) and Hispanic (-8.3{\textpm}9.3 dB) patients (vs. Whites [-5.5{\textpm}7.3 dB, p\&lt;0.001] or non-Hispanics [-6.2{\textpm}7.8 dB, p\&lt;0.001]). After controlling for age, gender and English proficiency, disparities in glaucoma severity at presentation were reduced, especially among Asian and Hispanic patients. Despite greater severity at presentation, Black patients had lower VF test frequency/person-years (1.07{\textpm}0.53) compared to Whites (1.12{\textpm}0.52, p=0.006) and worse VF MD progression (-0.43 dB/year, 95\% CI -0.67 to -0.28, p\&lt;0.001). In contrast, Hispanics had a higher VF frequency vs. non-Hispanics (1.18{\textpm}0.64 vs. 1.11{\textpm}0.52, p\&lt;0.001), and no difference in VF progression (p=0.77). CONCLUSIONS: Black, Asian and Hispanic patients had greater baseline severity vs. Whites. Unlike other groups, Black patients had a lower VF frequency vs. Whites and greater VF progression. Disparities in baseline severity were partially explained by English proficiency, especially for Asian and Hispanic patients.},
	keywords = {Disease Progression, ethnicity, Female, Glaucoma, Humans, Intraocular Pressure, Male, Retrospective Studies, Severity of Illness Index, Vision Disorders, Visual Field Tests, Visual Fields},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.05.023},
	author = {Halawa, Omar A and Jin, Qingying and Pasquale, Louis R and Kang, Jae H and Lorch, Alice C and Sobrin, Lucia and Miller, Joan W and Li, Yangjiani and Eslami, Mohammad and Wang, Mengyu and Zebardast, Nazlee and Tobias Elze}
}
@article {1709701,
	title = {Relationship between Claims-Based Frailty Index and Eye Care Utilization among Medicare Beneficiaries with Glaucoma},
	journal = {Ophthalmology},
	volume = {130},
	number = {6},
	year = {2023},
	month = {2023 Jun},
	pages = {646-654},
	abstract = {PURPOSE: To determine differences in eye care utilization by frailty levels among Medicare beneficiaries with glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Medicare fee-for-service beneficiaries over 65 years of age with glaucoma, identified using International Classification of Diseases codes before July 1,\&nbsp;2014. METHODS: By using a validated claims-based frailty index (range, 0-1), beneficiaries were classified as nonfrail/prefrail (0-0.19), mildly frail (0.20-0.29), and moderate-to-severely frail (>= 0.30). Negative binomial regression analyses were used to estimate incident rate ratios (IRRs) of eye care utilization by frailty levels between July 1, 2014, and December 31,\&nbsp;2016. MAIN OUTCOME MEASURES: Current Procedural Terminology codes for eye examinations and eye care-related office visits; eye care-related inpatient and emergency department (ED) encounters; eye care-related nursing facility and home-visit encounters; visual field (VF) and retinal nerve fiber layer (RNFL) OCT tests; and selective laser trabeculoplasties (SLTs) and glaucoma surgeries. RESULTS: Among 76 260 Medicare beneficiaries with glaucoma, the mean age was 78.9 years (standard deviation, 7.8), female beneficiaries constituted 60.5\%, and 78.7\% of beneficiaries self-identified as non-Hispanic White. According to a claims-based frailty index, 79.5\% of beneficiaries were nonfrail/prefrail, 17.1\% were mildly frail, and 3.4\% were moderate-to-severely frail. Moderate-to-severely frail beneficiaries were less likely than nonfrail/prefrail beneficiaries to have outpatient encounters (IRR, 0.85, 95\% confidence interval [CI], 0.83-0.88); VF tests (IRR, 0.64, 95\% CI, 0.60-0.67); RNFL OCT tests (IRR, 0.77, 95\% CI, 0.73-0.81); SLT (IRR, 0.74, 95\% CI, 0.60-0.92); and glaucoma surgery (IRR, 0.74, 95\% CI 0.55-0.99), after adjusting for age, gender, glaucoma severity, race, and socioeconomic status. Compared with nonfrail/prefrail beneficiaries, moderate-to-severely frail beneficiaries had higher rates of inpatient/ED encounters (IRR, 5.03, 95\% CI, 2.36-10.71) and nursing facility/home-visit encounters (IRR, 34.89, 95\% CI, 14.82-82.13). CONCLUSIONS: Compared with nonfrail/prefrail Medicare beneficiaries with glaucoma, beneficiaries with moderate-to-severe frailty had lower rates of eye care utilization in the outpatient setting and higher rates of utilization in acute care settings. This suggests that frail patients may receive less disease monitoring and fewer interventions for their glaucoma management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Aged, Female, Frailty, Glaucoma, Humans, Medicare, Retrospective Studies, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.01.015},
	author = {Halawa, Omar A and Kang, Joyce and Parikh, Ayush A and Oh, Gahee and Glynn, Robert J and Friedman, David S and Kim, Dae Hyun and Zebardast, Nazlee}
}
@article {1608600,
	title = {Changing trends in ocular trauma during the COVID-19 pandemic in the USA},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {295-298},
	abstract = {BACKGROUND/AIMS: The COVID-19 pandemic has been associated with a decline in emergency department (ED) presentations for trauma. The purpose of this study is to compare the estimated number and characteristics of eye injuries in 2020, the year of the COVID-19 pandemic, to those in 2011-2019. METHODS: A stratified probability sample of US ED-treated eye injuries was used to calculate the estimated annual number and incidence of these injuries in 2020, the year of the pandemic, and 2011-2019 (prepandemic years). Two-sample t-tests and Pearson χ2 were used to assess differences in demographics and injury characteristics. For multiple comparisons, Bonferroni correction was applied. RESULTS: The estimated number of ED-treated eye injuries per year was 152 957 (95\% CI 132 637 to 176 153) in 2020 and 194 142 (95\% CI 191 566 to 196 401) in 2011-2019. The annual incidence of ED-treated eye injuries was lower in 2020, at 46 per 100 000 population than in 2011-2019, at 62 per 100 000 per year (p\&lt;0.001). In 2020 vs 2011-2019, there was a higher incidence of ruptured globes (0.5 per 100 000 vs 0.3 per 100 000 per year, p\&lt;0.001), hyphemas (0.6 per 100 000 vs 0.4 per 100 000 per year, p\&lt;0.001), lacerations (1.0 per 100 000 in 2020 vs 0.8 per 100 000 per year, p\&lt;0.001) and orbital fractures (0.3 per 100 000 vs 0.03). CONCLUSION: The estimated incidence of eye injuries presenting to the ED was significantly lower in 2020 than in 2011-2019, but there was a higher estimated incidence of severe eye injuries. Changes in living and work environments due to the COVID-19 pandemic were likely associated with the differences in ocular trauma presentations observed in this study.},
	keywords = {COVID-19, Emergency Service, Hospital, Eye Injuries, Humans, Incidence, Pandemics, Retrospective Studies, United States},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-319627},
	author = {Halawa, Omar A and Friedman, David S and Roldan, Ana M and Zebardast, Nazlee}
}
@article {1642034,
	title = {Factors associated with glaucoma-specific quality of life in a US glaucoma clinic in a pilot implementation of an online computerised adaptive test (GlauCAT)},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {1079-1085},
	abstract = {OBJECTIVES: Measure quality of life (QoL) outcomes using a novel computerised adaptive test in a clinical setting, and determine the social and demographic factors associated with specific QoL domains in patients with glaucoma. DESIGN: Cross-sectional study between July 2020 and April 2021. PARTICIPANTS: English-speaking adults presenting to glaucoma clinic. Patients with cognitive impairment on a six-item cognitive impairment screen or with intraocular surgery within 90 days prior to presentation were excluded. RESULTS: Of 206 patients surveyed, mean age was 64.8 years (SD 15.2), 122 (56.7\%) were female and 159 (74.7\%) were white. On multivariable regression, visual acuity was associated with greater activity limitation (β=-2.8 points, 95\% CI -3.8 to -1.8, p\&lt;0.001) and worse mobility (β=-2.1 points, 95\% CI -3.2 to -0.9, p\&lt;0.001), while poorer visual field (VF) mean deviation was associated with lower scores on the emotional well-being domain (β=-2.4 points, 95\% CI -4.6 to -0.3, p=0.03). Glaucoma suspects and those with early VF defects had higher QoL scores than those with severe glaucoma in the following domains: activity limitation (88.5{\textpm}14.6 vs 74.3{\textpm}21.9, respectively, p\&lt;0.001), mobility (91.0{\textpm}12.5 vs 80.0{\textpm}25.3, respectively, p=0.005) and concerns domains (82.2{\textpm}13.9 vs 72.5 5{\textpm}18.9, respectively, p=0.01). CONCLUSIONS: In a busy glaucoma clinic where QoL was measured with online adaptive tests for glaucoma, we found that several demographic and clinical variables are associated with lower domain scores, suggesting that patients with predisposing demographic and clinical factors are at a higher risk of worse QoL.},
	keywords = {Adult, Cross-Sectional Studies, Female, Glaucoma, Humans, Male, Middle Aged, Ocular Hypertension, Quality of Life, Surveys and Questionnaires, Visual Fields},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2022-321145},
	author = {Halawa, Omar A and Roldan, Ana M and Meshkin, Ryan S and Zebardast, Nazlee and Fenwick, Eva K and Lamoureux, Ecosse Luc and Friedman, David S}
}
@article {1651350,
	title = {Reply},
	journal = {Ophthalmology},
	year = {2022},
	author = {Halawa, OA and Kolli, A and Oh, G and Mitchell, WG and Glynn, R J and Kim, D. H. and Friedman, D S and Zebardast, N}
}
@article {1598063,
	title = {Population-Based Utility of van Herick Grading for Angle-Closure Detection},
	journal = {Ophthalmology},
	volume = {128},
	number = {12},
	year = {2021},
	month = {2021 12},
	pages = {1779-1782},
	keywords = {Anterior Chamber, Diagnostic Techniques, Ophthalmological, Female, Glaucoma, Angle-Closure, Gonioscopy, Humans, Limbus Corneae, Male, Middle Aged, ROC Curve, Sensitivity and Specificity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.06.010},
	author = {Halawa, Omar A and Zebardast, Nazlee and Kolli, Ajay and Foster, Paul J and He, Mingguang and Aung, Tin and Friedman, David S}
}
@article {1282121,
	title = {A Novel Adaptive Deformable Model for Automated Optic Disc and Cup Segmentation to Aid Glaucoma Diagnosis},
	journal = {J Med Syst},
	volume = {42},
	number = {1},
	year = {2017},
	month = {2017 Dec 07},
	pages = {20},
	abstract = {This paper proposes a novel Adaptive Region-based Edge Smoothing Model (ARESM) for automatic boundary detection of optic disc and cup to aid automatic glaucoma diagnosis. The novelty of our approach consists of two aspects: 1) automatic detection of initial optimum object boundary based on a Region Classification Model (RCM) in a pixel-level multidimensional feature space; 2) an Adaptive Edge Smoothing Update model (AESU) of contour points (e.g. misclassified or irregular points) based on iterative force field calculations with contours obtained from the RCM by minimising energy function (an approach that does not require predefined geometric templates to guide auto-segmentation). Such an approach provides robustness in capturing a range of variations and shapes. We have conducted a comprehensive comparison between our approach and the state-of-the-art existing deformable models and validated it with publicly available datasets. The experimental evaluation shows that the proposed approach significantly outperforms existing methods. The generality of the proposed approach will enable segmentation and detection of other object boundaries and provide added value in the field of medical image processing and analysis.},
	issn = {1573-689X},
	doi = {10.1007/s10916-017-0859-4},
	author = {Haleem, Muhammad Salman and Han, Liangxiu and van Hemert, Jano and Li, Baihua and Fleming, Alan and Pasquale, Louis R and Song, Brian J}
}
@article {688606,
	title = {Regional Image Features Model for Automatic Classification between Normal and Glaucoma in Fundus and Scanning Laser Ophthalmoscopy (SLO) Images.},
	journal = {J Med Syst},
	volume = {40},
	number = {6},
	year = {2016},
	month = {2016 Jun},
	pages = {132},
	abstract = {Glaucoma is one of the leading causes of blindness worldwide. There is no cure for glaucoma but detection at its earliest stage and subsequent treatment can aid patients to prevent blindness. Currently, optic disc and retinal imaging facilitates glaucoma detection but this method requires manual post-imaging modifications that are time-consuming and subjective to image assessment by human observers. Therefore, it is necessary to automate this process. In this work, we have first proposed a novel computer aided approach for automatic glaucoma detection based on Regional Image Features Model (RIFM) which can automatically perform classification between normal and glaucoma images on the basis of regional information. Different from all the existing methods, our approach can extract both geometric (e.g. morphometric properties) and non-geometric based properties (e.g. pixel appearance/intensity values, texture) from images and significantly increase the classification performance. Our proposed approach consists of three new major contributions including automatic localisation of optic disc, automatic segmentation of disc, and classification between normal and glaucoma based on geometric and non-geometric properties of different regions of an image. We have compared our method with existing approaches and tested it on both fundus and Scanning laser ophthalmoscopy (SLO) images. The experimental results show that our proposed approach outperforms the state-of-the-art approaches using either geometric or non-geometric properties. The overall glaucoma classification accuracy for fundus images is 94.4 \% and accuracy of detection of suspicion of glaucoma in SLO images is 93.9 \%.},
	issn = {1573-689X},
	doi = {10.1007/s10916-016-0482-9},
	author = {Haleem, Muhammad Salman and Han, Liangxiu and van Hemert, Jano and Fleming, Alan and Pasquale, Louis R and Silva, Paolo S and Song, Brian J and Aiello, Lloyd Paul}
}
@article {669266,
	title = {Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy.},
	journal = {Antioxid Redox Signal},
	volume = {24},
	number = {18},
	year = {2016},
	month = {2016 Jun 20},
	pages = {1072-83},
	abstract = {AIMS: Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. RESULTS: We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in ΔΨm and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. INNOVATION: This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. CONCLUSION: MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release. Antioxid. Redox Signal. 24, 1072-1083.},
	issn = {1557-7716},
	doi = {10.1089/ars.2015.6532},
	author = {Halilovic, Adna and Schmedt, Thore and Benischke, Anne-Sophie and Hamill, Cecily and Chen, Yuming and Santos, Janine Hertzog and Jurkunas, Ula V}
}
@article {1511492,
	title = {The effects of systemic cyclosporine in acute Stevens-Johnson syndrome/toxic epidermal necrolysis on ocular disease},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 May 20},
	abstract = {PURPOSE: To evaluate the effect of systemic cyclosporine (CsA) on ocular disease in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients. METHODS: In this retrospective, comparative cohort study at a single center, patients with a diagnosis of SJS/TEN and with at least 3 months of follow up were divided into two groups: those who received systemic CsA and those who did not receive systemic CsA. Best-corrected visual acuity (BCVA) and chronic ocular surface complications score (COCS) at final follow-up were compared between the two groups. RESULTS: The median age and follow-up period of patients was 29 years (range, 1.5-71 years) and 16.8 months (range, 3.67-91.58 months), respectively. BCVA, COCS, meibomian gland dysfunction, limbal stem cell deficiency, and the need for mucous membrane grafting and scleral lenses were not significantly different between patients who received systemic CsA as compared to patients who did not receive systemic CsA. CONCLUSIONS: In this small cohort of patients with SJS/TEN, we could identify no association between the use of systemic CsA as a component of their initial therapy and chronic ocular complications.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.05.003},
	author = {Hall, Leangelo N and Shanbhag, Swapna S and Rashad, Ramy and Chodosh, James and Saeed, Hajirah N}
}
@article {1761966,
	title = {The Epidemiology and Risk Factors for the Progression of Sympathetic Ophthalmia in the United States: An IRIS Registry Analysis},
	journal = {Am J Ophthalmol},
	volume = {258},
	year = {2024},
	month = {2024 Feb},
	pages = {208-216},
	abstract = {PURPOSE: To investigate the demographic and clinical characteristics of patients with sympathetic ophthalmia (SO) and define the risk factors for its incidence following trauma and ophthalmic procedures. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the American Academy of Ophthalmology{\textquoteright}s (Academy) IRIS Registry (Intelligent Research in Sight) who were (n=1523) or were not diagnosed with SO following a documented procedure or trauma between January 1, 2013, and December 31, 2019. METHODS: Multiple demographic and clinical factors were collected, descriptive statistics and prevalence were calculated, and multivariate linear regression models were fit to the data. MAIN OUTCOME MEASURES: Prevalence of SO, demographic and clinical characteristics, and beta coefficient (β) estimates of demographic and clinical characteristics impacting time to SO onset after procedure (Procedure Only cohort) or trauma (Trauma cohort). RESULTS: Of 65,348,409 distinct IRIS Registry patients, 1523 (0.0023\%) were diagnosed with SO between 2013 and 2019, and also had a documented preceding trauma or procedure. Of these, 927 (60.87\%) were female, 1336 (87.72\%) belonged to the Procedure Only cohort, and 187 (12.28\%) belonged to the Trauma cohort. The prevalence of SO after trauma was 0.0207\%, whereas after procedures it was 0.0124\%. The highest risk of procedure-related SO was seen in patients with history of "other anterior segment" (0.122\%) followed by glaucoma (0.066\%) procedures, whereas the lowest prevalence was noted with cataract surgeries (0.011\%). The average time to onset of SO across both cohorts combined was 527.44 ({\textpm}715.60) days, with statistically significant differences between the 2 cohorts (P \&lt; .001). On average, the time to onset from inciting event to SO was shorter with increasing age, by 9.02 (95\% CI: -11.96, -6.08) days for every 1-year increase. CONCLUSIONS: SO following trauma and ophthalmic procedure is potentially rarer than previously reported, as measured in this large ophthalmic medical record database. Female sex may be a risk factor for SO. Older age may be a risk factor for quicker onset. These findings can guide clinical decision-making and management.},
	keywords = {Female, Glaucoma, Humans, Infant, Newborn, Male, Ophthalmia, Sympathetic, Registries, Retrospective Studies, Risk Factors, United States},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.09.011},
	author = {Hall, Nathan and Douglas, Vivian Paraskevi and Ivanov, Alexander and Ross, Connor and Tobias Elze and Kempen, John H and Miller, Joan W and Sobrin, Lucia and Lorch, Alice}
}
@article {1638557,
	title = {Risk factors for glaucoma drainage device revision or removal using the IRIS Registry},
	journal = {Am J Ophthalmol},
	year = {2022},
	month = {2022 Apr 02},
	abstract = {PURPOSE: To elucidate risk factors for revision or removal of glaucoma drainage devices (GDD) in glaucoma patients in the United States. DESIGN: Retrospective cohort study. METHODS: IRIS{\textregistered} Registry (Intelligent Research in Sight) patients who underwent GDD insertion between 01/01/2013 and 12/31/2018 were included. Various demographic and clinical factors were collected. Kaplan-Meier (KM) survival plots, Cox proportional-hazard models utilizing Firth{\textquoteright}s Penalized Likelihood (CRFPL), and multivariate linear regression models were used. The main outcome measures were hazard ratios (HRs) and beta coefficient (β) estimates. RESULTS: 44,330 distinct patients underwent at least one GDD implantation, and 3,354 of these underwent subsequent GDD revision or removal surgery. With failure defined as GDD revision/removal, factors significantly associated with decreased failure included unknown race (HR=0.83; p=0.004) and unknown ethnicity (HR=0.68; p\&lt;0.001). Factors associated with increased risk of GDD revision/removal surgery included presence of chronic angle closure glaucoma (HR=1.32; p\&lt;0.001) and dry eye disease (HR=1.30; p=0.007). Additionally, factors associated with a decreased average time (in days) to GDD revision/removal included male sex (β=-25.96; p=0.044), unknown race (β=-55.28; p=0.013), and right-eye laterality (β=-38.67; p=0.026). Factors associated with an increased average time to GDD revision/removal included having a history of a past eye procedure (β=104.83; p\&lt;0.001) and being an active smoker (β=38.15; p=0.024). CONCLUSIONS: The size and scope of the IRIS Registry allows for detection of subtle associations between risk factors and GDD revision or removal surgery. Aforementioned demographic and clinical factors may all have an impact on GDD longevity and can inform the treatment options available for glaucoma patients.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.03.029},
	author = {Hall, Nathan E and Chang, Enchi K and Samuel, Sandy and Gupta, Sanchay and Klug, Emma and Tobias Elze and Lorch, Alice C and Miller, Joan W and Sol{\'a}-Del Valle, David}
}
@article {1638573,
	title = {Long-Term Outcomes of Big Bubble Deep Anterior Lamellar Keratoplasty in Mucopolysaccharidoses: A Retrospective Case Series and Review of the Literature},
	journal = {Cornea},
	volume = {41},
	number = {7},
	year = {2022},
	month = {2022 Jul 01},
	pages = {809-814},
	abstract = {PURPOSE: The purpose of this study was to report the long-term surgical and visual outcomes of patients with mucopolysaccharidoses (MPS) after big bubble deep anterior lamellar keratoplasty (BB-DALK). METHODS: This was a retrospective case series of patients with MPS who underwent BB-DALK at a single academic institution. All patients had corneal clouding secondary to MPS limiting visual acuity for which keratoplasty was indicated. Each patient was evaluated and underwent surgery by a single surgeon. Reported data included age at keratoplasty, sex, MPS type, best spectacle-corrected visual acuity, change in pachymetry, ocular comorbidities, surgical complications, and MPS-related medication use. RESULTS: Outcomes of 12 eyes from 7 patients with MPS type I (Hurler, Scheie, and Hurler-Scheie) are reported using the newest nomenclature. The mean follow-up was 5.58 years (range: 1-10 years). All cases underwent BB-DALK with a type 1 big bubble during the surgery. Two cases (16.6\%) required rebubbling because of partial Descemet membrane detachment. One case was complicated by a suture abscess and required a penetrating keratoplasty. No episodes of rejection occurred. Statistically significant improvement in the best spectacle-corrected visual acuity (from a mean 0.85-0.33 logarithm of the minimum angle of resolution, P = logarithm of the minimum angle of resolution 0.0054) and pachymetry (mean reduction of -145.4 μm, P = 0.0018) was observed. CONCLUSIONS: BB-DALK seems to be an acceptable long-term surgical option in patients with MPS. Our findings suggest that this technique is reproducible and can achieve clear corneal grafts with good visual results on a long-term follow-up.},
	keywords = {Corneal Diseases, Corneal Transplantation, Follow-Up Studies, Humans, Keratoconus, Keratoplasty, Penetrating, Mucopolysaccharidoses, Mucopolysaccharidosis I, Retrospective Studies, Treatment Outcome},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003041},
	author = {Hallal, Ramon and Armstrong, Grayson W and Pineda, Roberto}
}
@article {1517166,
	title = {Late-Onset Retinal Findings and Complications in Untreated Retinopathy of Prematurity},
	journal = {Ophthalmol Retina},
	volume = {4},
	number = {6},
	year = {2020},
	month = {2020 06},
	pages = {602-612},
	abstract = {PURPOSE: To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy. DESIGN: Retrospective, nonconsecutive, noncomparative, multicenter case series. PARTICIPANTS: Three hundred sixty-three eyes of 186 patients. METHODS: Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings. MAIN OUTCOME MEASURES: Rate of RDs and factors conferring a higher risk of RDs. RESULTS: The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0\%), atrophic holes in 126 eyes (34.7\%), retinal tears in 111 eyes (30.6\%), RDs in 140 eyes (38.6 \%), tractional retinoschisis in 44 eyes (11.9\%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5\%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2\%) showed leakage and 16 eyes (14.2\%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6\% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P \&lt; 0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P\&nbsp;= 0.009). CONCLUSIONS: Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications.},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.12.015},
	author = {Hamad, Abdualrahman E and Moinuddin, Omar and Blair, Michael P and Schechet, Sidney A and Shapiro, Michael J and Quiram, Polly A and Mammo, Danny A and Berrocal, Audina M and Prakhunhungsit, Supalert and Cernichiaro-Espinosa, Linda A and Mukai, Shizuo and Yonekawa, Yoshihiro and Ung, Cindy and Holz, Eric R and Harper, C Armitage and Young, Ryan C and Besirli, Cagri G and Nagiel, Aaron and Lee, Thomas C and Gupta, Mrinali P and Walsh, Mark K and Khawly, Joseph A and Campbell, J Peter and Kychenthal, Andres and Nudleman, Eric D and Robinson, Josh E and Hartnett, Mary Elizabeth and Calvo, Charles M and Chang, Emmanuel Y}
}
@article {1798371,
	title = {Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma},
	journal = {Nat Commun},
	volume = {15},
	number = {1},
	year = {2024},
	month = {2024 Jan 09},
	pages = {396},
	abstract = {Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of \&gt;240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60\% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.},
	keywords = {Causality, Gene Expression Regulation, Genome-Wide Association Study, Glaucoma, Glaucoma, Open-Angle, Humans},
	issn = {2041-1723},
	doi = {10.1038/s41467-023-44380-y},
	author = {Hamel, Andrew R and Yan, Wenjun and Rouhana, John M and Monovarfeshani, Aboozar and Jiang, Xinyi and Mehta, Puja A and Advani, Jayshree and Luo, Yuyang and Liang, Qingnan and Rajasundaram, Skanda and Shrivastava, Arushi and Duchinski, Katherine and Mantena, Sreekar and Wang, Jiali and van Zyl, Tav{\'e} and Pasquale, Louis R and Swaroop, Anand and Gharahkhani, Puya and Khawaja, Anthony P and Macgregor, Stuart and Chen, Rui and Vitart, Veronique and Sanes, Joshua R and Wiggs, Janey L and Segr{\`e}, Ayellet V}
}
@article {560146,
	title = {Special Commentary: Food and Drug Administration, American Academy of Ophthalmology, American Academy of Optometry, American Optometric Association and the Contact Lens Association of Ophthalmologists Cosponsored Workshop: Revamping Microbiological Test M},
	journal = {Eye Contact Lens},
	year = {2015},
	month = {2015 Oct 13},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000205},
	author = {Hampton, Denise and Tarver, Michelle E and Jacobs, Deborah S and Szczotka-Flynn, Loretta and Steinemann, Thomas and Dhaliwal, Deepinder and Due{\~n}as, Michael R and Jeng, Bennie H and Eydelman, Malvina}
}
@article {1109801,
	title = {Widespread effects of clinically unilateral focal nerve injuries},
	journal = {Pain},
	volume = {158},
	number = {6},
	year = {2017},
	month = {2017 06},
	pages = {1175-1176},
	issn = {1872-6623},
	doi = {10.1097/j.pain.0000000000000867},
	author = {Hamrah, Pedram and Sahin, Afsun and Oaklander, Anne Louise}
}
@article {1364610,
	title = {Cellular changes of the corneal epithelium and stroma in herpes simplex keratitis: an in vivo confocal microscopy study},
	journal = {Ophthalmology},
	volume = {119},
	number = {9},
	year = {2012},
	month = {2012 Sep},
	pages = {1791-7},
	abstract = {PURPOSE: To analyze the morphologic features of corneal epithelial cells and keratocytes by in vivo confocal microscopy in patients with herpes simplex keratitis (HSK) as associated with corneal innervation. DESIGN: Prospective, cross-sectional, controlled, single-center study. PARTICIPANTS: Thirty-one eyes with the diagnosis HSK and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). METHODS: In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (\&gt;5.5 cm), mild (\&gt;2.5-5.5 cm), and severe (\&lt;2.5 cm) loss of sensation. MAIN OUTCOME MEASURES: Changes in morphologic features and density of the superficial and basal epithelial cells, as well as stromal keratocytes, were assessed by 2 masked observers. Changes were correlated to corneal sensation, number of nerves, and total length of nerves. RESULTS: There was a significant and gradual decrease in the density of superficial epithelial cells in HSK eyes, with 852.50 {\textpm} 24.4 cells/mm(2) in eyes with severe sensation loss and 2435.23 {\textpm} 224.3 cells/mm(2) in control eyes (P = 0.008). Superficial epithelial cell size was 2.5-fold larger in HSK eyes (835.3 μm(2)) compared with contralateral or normal eyes (407.4 μm(2); P = 0.003). A significant number of hyperreflective desquamating superficial epithelial cells were present in HSK eyes with normal (6.4\%), mild (29.1\%), and severe (52.2\%) loss of sensation, but were absent in controls. The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients and controls. Changes in superficial epithelial cell density and morphologic features correlated strongly with total nerve length, number, and corneal sensation. Scans of contralateral eyes did not show any significant epithelial or stromal changes compared with controls. CONCLUSIONS: In vivo confocal microscopy reveals profound HSK-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. This study demonstrated that these changes correlate strongly with changes in corneal innervation.},
	keywords = {Cell Count, Cell Size, Cornea, Corneal Keratocytes, Corneal Stroma, Cranial Nerve Diseases, Cross-Sectional Studies, Epithelium, Corneal, Female, Humans, Keratitis, Herpetic, Male, Microscopy, Confocal, Middle Aged, Ophthalmic Nerve, Prospective Studies},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2012.03.005},
	author = {Hamrah, Pedram and Sahin, Afsun and Dastjerdi, Mohammad H and Shahatit, Bashar M and Bayhan, Hasan A and Dana, Reza and Pavan-Langston, Deborah}
}
@article {959401,
	title = {Corneal Nerve and Epithelial Cell Alterations in Corneal Allodynia: An In Vivo Confocal Microscopy Case Series.},
	journal = {Ocul Surf},
	volume = {15},
	number = {1},
	year = {2017},
	month = {2017 Jan},
	pages = {139-151},
	abstract = {PURPOSE: To investigate morphological changes of the corneal epithelium and subbasal nerves in patients with corneal allodynia using in\&nbsp;vivo confocal microscopy (IVCM). DESIGN: Case-control study of patients with corneal allodynia and healthy controls. METHODS: Ten eyes of six patients were diagnosed with corneal allodynia at a single center and compared to fifteen healthy eyes. IVCM of the central cornea was performed on all subjects and controls. Images were retrospectively analyzed numbers of total corneal subbasal nerves, main trunks and branches, total nerve length and density, nerve branching, and tortuosity, superficial and basal epithelial cell densities, and superficial epithelial cell size. RESULTS: Corneal allodynia was seen in patients with dry eye disease, recurrent corneal erosion syndrome, exposure to ultraviolet radiation, and Accutane use. Compared to controls, patients with corneal allodynia had a significant decrease in the total numbers of subbasal nerves (P=.014), nerve branches (P=.006), total nerve length (P=.0029), total nerve density (P=.0029) and superficial and basal epithelial cell densities (P=.0004, P=.0036) with an increase in superficial epithelial cell size (P=.016). There were no statistically significant differences in the number of subbasal nerve main trunks (P=.09), nerve branching (P=.21), and nerve tortuosity (P=.05). CONCLUSIONS: Corneal IVCM enables near-histological visualization and quantification of the cellular and neural changes in corneal allodynia. Regardless of etiology, corneal allodynia is associated with decreased corneal epithelial cell densities, increased epithelial cell size, and decreased numbers and lengths of subbasal nerves despite an unremarkable slit-lamp examination. Therefore, IVCM may be useful in the management of patients with corneal allodynia.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2016.10.002},
	author = {Hamrah, Pedram and Qazi, Yureeda and Shahatit, Bashar and Dastjerdi, Mohammad H and Pavan-Langston, Deborah and Jacobs, Deborah S and Rosenthal, Perry}
}
@article {1363118,
	title = {Unilateral herpes zoster ophthalmicus results in bilateral corneal nerve alteration: an in vivo confocal microscopy study},
	journal = {Ophthalmology},
	volume = {120},
	number = {1},
	year = {2013},
	month = {2013 Jan},
	pages = {40-7},
	abstract = {PURPOSE: Herpes zoster ophthalmicus (HZO), thought to be a unilateral disease, results in loss of corneal sensation, leading to neurotrophic keratopathy. This study aimed to analyze bilateral corneal nerve changes in patients with HZO by in vivo confocal microscopy (IVCM) and their correlation with corneal sensation as a measure of nerve function.

DESIGN: Prospective, cross-sectional, controlled, single-center study.

PARTICIPANTS: Twenty-seven eyes with the diagnosis of HZO and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15).

METHODS: In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (,
	keywords = {Cornea, Cranial Nerve Diseases, Cross-Sectional Studies, Female, Herpes Zoster Ophthalmicus, Humans, Male, Microscopy, Confocal, Middle Aged, Prospective Studies, Single-Blind Method, Trigeminal Ganglion},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2012.07.036},
	author = {Hamrah, Pedram and Cruzat, Andrea and Dastjerdi, Mohammad H and Pr{\"u}ss, Harald and Zheng, Lixin and Shahatit, Bashar M and Bayhan, Hasan A and Dana, Reza and Pavan-Langston, Deborah}
}
@article {382576,
	title = {InVivo confocal microscopic changes of the corneal epithelium and stroma in patients with herpes zoster ophthalmicus.},
	journal = {Am J Ophthalmol},
	volume = {159},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {1036-1044.e1},
	abstract = {PURPOSE: To analyze the density and morphology of corneal epithelial cells and keratocytes by in\&nbsp;vivo confocal microscopy (IVCM) in patients with herpes zoster ophthalmicus (HZO) as associated with corneal innervation. DESIGN: Prospective, controlled and masked cross-sectional study. METHODS: setting: Single-center study. PATIENTS: Thirty eyes with the diagnosis HZO and their contralateral clinically unaffected eyes, 15 eyes of 15 normal controls. intervention procedures: In\&nbsp;vivo confocal microscopy and corneal esthesiometry of the central cornea. MAIN OUTCOME MEASURES: Changes in morphology and density of the superficial and basal epithelial cells and stromal keratocytes, and correlation with corneal sensation. RESULTS: The density of superficial epithelial cells in HZO eyes with severe sensation loss (766.5 {\textpm} 25.2 cells/mm(2)) was significantly lower than both healthy control eyes (1450.23 {\textpm} 150.83 cells/mm(2)) and contralateral unaffected eyes (1974.13 {\textpm} 298.24 cells/mm(2)) (P\&nbsp;= .003). Superficial epithelial cell size (1162.5\&nbsp;μm(2)) was significantly larger in HZO eyes with severe loss of sensation, as compared to contralateral (441.46 {\textpm} 298.14) or healthy eyes (407.4\&nbsp;{\textpm} 47.2μm(2); all P \&lt; .05). The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients, controls, and contralateral unaffected eyes. Changes in superficial epithelial cell density and morphology correlated strongly with corneal sensation. CONCLUSIONS: In\&nbsp;vivo confocal microscopy reveals profound HZO-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. We demonstrate that these changes strongly correlate with changes in corneal innervation in eyes affected by HZO.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.03.003},
	author = {Hamrah, Pedram and Sahin, Afsun and Dastjerdi, Mohammad H and Shahatit, Bashar M and Bayhan, Hasan A and Dana, Reza and Pavan-Langston, Deborah}
}
@article {1549006,
	title = {Capilliposide B blocks VEGF-induced angiogenesis in vitro in primary human retinal microvascular endothelial cells},
	journal = {Biomed Pharmacother},
	volume = {133},
	year = {2021},
	month = {2021 Jan},
	pages = {110999},
	abstract = {Abnormal angiogenesis is associated with intraocular diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, and current therapies for these eye diseases are not satisfactory. The purpose of this study was to determine whether capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, can inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis signaling events and cellular responses in primary human retinal microvascular endothelial cells (HRECs). Our study revealed that the capilliposide B IC for HRECs was 8.5 μM at 72 h and that 1 μM capilliposide B specifically inhibited VEGF-induced activation of VEGFR2 and its downstream signaling enzymes Akt and Erk. In addition, we discovered that this chemical effectively blocked VEGF-stimulated proliferation, migration and tube formation of the HRECs, suggesting that capilliposide B is a promising prophylactic for angiogenesis-associated diseases such as proliferative diabetic retinopathy.},
	issn = {1950-6007},
	doi = {10.1016/j.biopha.2020.110999},
	author = {Han, Haote and Yang, Yanhui and Wu, Zhipan and Liu, Bing and Dong, Lijun and Deng, Hongwei and Tian, Jingkui and Lei, Hetian}
}
@article {1302174,
	title = {Effect of brimonidine, an α2 adrenergic agonist, on human meibomian gland epithelial cells},
	journal = {Exp Eye Res},
	volume = {170},
	year = {2018},
	month = {2018 May},
	pages = {20-28},
	abstract = {We recently discovered that the anti-glaucoma pharmaceuticals timolol, a β adrenergic antagonist, and pilocarpine, a cholinergic compound, negatively influence the morphology, proliferative capacity and survival of human meibomian gland epithelial cells (HMGECs). We hypothesize that another class of anti-glaucoma drugs, the α2 adrenergic agonists, also acts directly on HMGECs to affect their structure and function. We tested this hypothesis. Immortalized (i) HMGECs were cultured with brimonidine, as well as clonidine (α2 agonist), phenylephrine (α1 agonist), RX821002 (inverse α2 agonist) and MK912 (neutral α2 agonist) for up to 7 days. Cells were counted with a hemocytometer, and evaluated for morphology, signaling pathway activity, protein biomarker expression, and the accumulation of neutral lipids, phospholipids and lysosomes. Our findings demonstrate that brimondine treatment induces a dose-dependent decrease in Akt signaling and proliferation of iHMGECs. In contrast, brimonidine also promotes a dose-dependent differentiation of iHMGECs, including an increase in neutral lipid, phospholipid and lysosome levels. These effects were paralleled by an inhibition of p38 signaling, and duplicated by cellular exposure to clonidine, but not phenylephrine. Brimonidine also enhanced the cellular content of sterol regulatory binding protein-1, a master regulator of lipid synthesis. Of particular interest, the putative α2 antagonists, RX821002 and MK912, did not interfere with brimonidine action, but rather stimulated IHMGEC differentiation. Our results support our hypothesis and demonstrate that α2 adrenergic agonists act directly on iHMGECs. However, these compounds do not elicit an overall negative effect. Rather, the α2 agonists promote the differentiation of iHMGECs.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.02.009},
	author = {Han, Xi and Liu, Yang and Kam, Wendy R and Sullivan, David A}
}
@article {1709766,
	title = {Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration},
	journal = {Cell Rep Med},
	volume = {4},
	number = {7},
	year = {2023},
	month = {2023 Jul 18},
	pages = {101085},
	abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.},
	keywords = {Aged, Bayes Theorem, Genome-Wide Association Study, Humans, Macular Degeneration, Metabolome, Metabolomics},
	issn = {2666-3791},
	doi = {10.1016/j.xcrm.2023.101085},
	author = {Han, Xikun and Lains, Ines and Li, Jun and Li, Jinglun and Chen, Yiheng and Yu, Bing and Qi, Qibin and Boerwinkle, Eric and Kaplan, Robert and Thyagarajan, Bharat and Daviglus, Martha and Joslin, Charlotte E and Cai, Jianwen and Guasch-Ferr{\'e}, Marta and Tobias, Deirdre K and Rimm, Eric and Ascherio, Alberto and Costenbader, Karen and Karlson, Elizabeth and Mucci, Lorelei and Eliassen, A Heather and Zeleznik, Oana and Miller, John and Vavvas, Demetrios G and Kim, Ivana K and Silva, Rufino and Miller, Joan and Hu, Frank and Willett, Walter and Lasky-Su, Jessica and Kraft, Peter and Richards, J Brent and Macgregor, Stuart and Husain, Deeba and Liang, Liming}
}
@article {1511485,
	title = {The Carbonic Anhydrase Inhibitor Dorzolamide Stimulates the Differentiation of Human Meibomian Gland Epithelial Cells},
	journal = {Curr Eye Res},
	volume = {45},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {1604-1610},
	abstract = {PURPOSE: Clinical studies have indicated that the long-term use of topical antiglaucoma drugs, such as carbonic anhydrase inhibitors (CAIs), may lead to meibomian gland dysfunction (MGD). We hypothesize that these adverse effects involve a direct influence on human MG epithelial cells (HMGECs). The purpose our present investigation was to test our hypothesis and determine whether exposure to dorzolamide, a CAI, impacts the proliferation, intracellular signaling and differentiation of HMGECs. MATERIALS AND METHODS: We cultured immortalized (i) HMGECs with vehicle or various concentrations of dorzolamide for 6\&nbsp;days. Cells were enumerated with a hemocytometer, and examined for their morphology, Akt signaling activity, accumulation of neutral lipids, phospholipids and lysosomes, and the expression of protein biomarkers for lipogenesis regulation, lysosomes and autophagosomes. RESULTS: Our results show that a high, 500\&nbsp;{\textmu}g/ml concentration of dorzolamide causes a significant decrease in Akt signaling and the proliferation of iHMGECs. However, the high dose of dorzolamide also promotes the differentiation of iHMGECs. This response features increases in the number of lysosomes, the accumulation of phospholipids, and the expression of the light chain 3A biomarker for autophagosomes. In contrast, the therapeutic amount (50\&nbsp;{\textmu}g/ml) of dorzolamide has no impact on the proliferative or differentiative abilities of iHMGECs. CONCLUSIONS: Our results support our hypothesis and demonstrate that the CAI dorzolamide does exert a direct influence on the proliferation and differentiation of iHMGECs. However, this effect is elicited only by a high, and not a therapeutic, amount of dorzolamide. AKT: phosphoinositide 3-kinase-protein kinase B; BPE: bovine pituitary extract; CAD: cationic amphiphilic drug; DED: dry eye disease; DMEM/F12: 1:1 mixture of Dulbecco{\textquoteright}s modified Eagle{\textquoteright}s medium and Ham{\textquoteright}s F-12; EGF: epidermal growth factor; FBS: fetal bovine serum; iHMGECs: immortalized human meibomian gland epithelial cells; KSFM: keratinocyte serum-free medium; LAMP-1: lysosomal-associated membrane protein 1; LC3A: light chain 3A; MGD: meibomian gland dysfunction; SREBP-1: sterol regulatory element-binding protein 1.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2020.1772832},
	author = {Han, Xi and Yang, Shan and Kam, Wendy R and Sullivan, David A and Liu, Yang}
}
@article {1782231,
	title = {The effect of visual rivalry in peripheral head-mounted displays on mobility},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Nov 18},
	pages = {20199},
	abstract = {Recent head-mounted displays and smart glasses use vision multiplexing, an optical approach where two or more views are superimposed on each other. In vision multiplexing, augmented information is presented over an observer{\textquoteright}s natural field of view, providing field expansion and critical information during mobility situations like walking and driving. Yet despite its utility, vision multiplexing may produce visual rivalry, a phenomenon where perception alternates between the augmented information and the background scene for seconds at a time. To investigate, we compared the effect of different peripheral vision multiplexing configurations (unilateral opaque, unilateral see-through and bilateral see-through) on the detection of augmented information, incorporating at the same time real-world characteristics (target eccentricity, depth condition, and gaze movement) for a more realistic assessment. Results showed a persistently lower target detection rate in unilateral configurations than the bilateral configuration, suggesting a larger effect of binocular rivalry on target visibility. Nevertheless, this effect does become attenuated when more naturalistic elements are incorporated, and we discuss recommendations for vision multiplexing design and possible avenues for further research.},
	keywords = {Movement, Smart Glasses, Vision, Binocular, Visual Perception},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-47427-8},
	author = {Han, Shui{\textquoteright}Er and Kim, Sujin and Jung, Jae-Hyun}
}
@article {1016046,
	title = {Potential role of corneal epithelial cell-derived exosomes in corneal wound healing and neovascularization},
	journal = {Sci Rep},
	volume = {7},
	year = {2017},
	month = {2017 Feb 06},
	pages = {40548},
	abstract = {Specific factors from the corneal epithelium underlying the stimulation of stromal fibrosis and myofibroblast formation in corneal wound healing have not been fully elucidated. Given that exosomes are known to transfer bioactive molecules among cells and play crucial roles in wound healing, angiogenesis, and cancer, we hypothesized that corneal epithelial cell-derived exosomes may gain access to the underlying stromal fibroblasts upon disruption of the epithelial basement membrane and that they induce signaling events essential for corneal wound healing. In the present study, exosome-like vesicles were observed between corneal epithelial cells and the stroma during wound healing after corneal epithelial debridement. These vesicles were also found in the stroma following anterior stromal keratectomy, in which surgical removal of the epithelium, basement membrane, and anterior stroma was performed. Exosomes secreted by mouse corneal epithelial cells were found to fuse to keratocytes in vitro and to induce myofibroblast transformation. In addition, epithelial cell-derived exosomes induced endothelial cell proliferation and ex vivo aortic ring sprouting. Our results indicate that epithelial cell-derived exosomes mediate communication between corneal epithelial cells and corneal keratocytes as well as vascular endothelial cells. These findings demonstrate that epithelial-derived exosomes may be involved in corneal wound healing and neovascularization, and thus, may serve as targets for potential therapeutic interventions.},
	issn = {2045-2322},
	doi = {10.1038/srep40548},
	author = {Han, Kyu-Yeon and Tran, Jennifer A and Chang, Jin-Hong and Azar, Dimitri T and Zieske, James D}
}
@article {1608581,
	title = {Chalcomoracin prevents vitreous-induced activation of AKT and migration of retinal pigment epithelial cells},
	journal = {J Cell Mol Med},
	volume = {25},
	number = {19},
	year = {2021},
	month = {2021 Oct},
	pages = {9102-9111},
	abstract = {Retinal pigment epithelial (RPE) cells are the major cell type in the epi- or sub-retinal membranes in the pathogenesis of proliferative vitreoretinopathy (PVR), which is a blinding fibrotic eye disease and still short of effective medicine. The purpose of this study is to demonstrate whether Chalocomoracin (CMR), a novel purified compound from fungus-infected mulberry leaves, is able to inhibit vitreous-induced signalling events and cellular responses intrinsic to PVR. Our studies have revealed that the CMR IC50 for ARPE-19 cells is 35.5\&nbsp;μmol/L at 72\&nbsp;hours, and that 5\&nbsp;μmol/L CMR inhibits vitreous-induced Akt activation and p53 suppression; in addition, we have discovered that this chemical effectively blocks vitreous-stimulated proliferation, migration and contraction of ARPE-19 cells, suggesting that CMR is a promising PVR prophylactic.},
	issn = {1582-4934},
	doi = {10.1111/jcmm.16590},
	author = {Han, Haote and Yang, Yanhui and Liu, Bing and Tian, Jingkui and Dong, Lijun and Qi, Hui and Zhu, Wei and Wang, Jiantao and Lei, Hetian}
}
@article {1318861,
	title = {Word recognition: re-thinking prosthetic vision evaluation},
	journal = {J Neural Eng},
	volume = {15},
	number = {5},
	year = {2018},
	month = {2018 Oct},
	pages = {055003},
	abstract = {OBJECTIVE: Evaluations of vision prostheses and sensory substitution devices have frequently relied on repeated training and then testing with the same small set of items. These multiple forced-choice tasks produced above chance performance in blind users, but it is unclear if the observed performance represents restoration of vision that transfers to novel, untrained items. APPROACH: Here, we tested the generalizability of the forced-choice paradigm on discrimination of low-resolution word images. Extensive visual training was conducted with the same 10 words used in previous BrainPort tongue stimulation studies. The performance on these 10 words and an additional 50 words was measured before and after the training sessions. MAIN RESULTS: The results revealed minimal performance improvement with the untrained words, demonstrating instead pattern discrimination limited mostly to the trained words. SIGNIFICANCE: These findings highlight the need to reconsider current evaluation practices, in particular, the use of forced-choice paradigms with a few highly trained items. While appropriate for measuring the performance thresholds in acuity or contrast sensitivity of a functioning visual system, performance on such tasks cannot be taken to indicate restored spatial pattern vision.},
	issn = {1741-2552},
	doi = {10.1088/1741-2552/aac663},
	author = {Han, Shui{\textquoteright}Er and Qiu, Cheng and Lee, Kassandra R and Jung, Jae-Hyun and Peli, Eli}
}
@article {1709806,
	title = {Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci},
	journal = {Nat Genet},
	year = {2023},
	month = {2023 Jun 29},
	abstract = {Glaucoma, a leading cause of irreversible blindness, is a highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure and optic nerve head excavation damage quantified as the vertical cup-to-disc ratio. Here, since much of glaucoma heritability remains unexplained, we conducted a large-scale multitrait genome-wide association study in participants of European ancestry combining primary open-angle glaucoma and its two associated traits (total sample size over 600,000) to substantially improve genetic discovery power (263 loci). We further increased our power by then employing a multiancestry approach, which increased the number of independent risk loci to 312, with the vast majority replicating in a large independent cohort from 23andMe, Inc. (total sample size over 2.8 million; 296 loci replicated at P \&lt; 0.05, 240 after Bonferroni correction). Leveraging multiomics datasets, we identified many potential druggable genes, including neuro-protection targets likely to act via the optic nerve, a key advance for glaucoma because all existing drugs only target intraocular pressure. We further used Mendelian randomization and genetic correlation-based approaches to identify novel links to other complex traits, including immune-related diseases such as multiple sclerosis and systemic lupus erythematosus.},
	issn = {1546-1718},
	doi = {10.1038/s41588-023-01428-5},
	author = {Han, Xikun and Gharahkhani, Puya and Hamel, Andrew R and Ong, Jue Sheng and Renter{\'\i}a, Miguel E and Mehta, Puja and Dong, Xianjun and Pasutto, Francesca and Hammond, Christopher and Young, Terri L and Hysi, Pirro and Lotery, Andrew J and Jorgenson, Eric and Choquet, H{\'e}l{\`e}ne and Hauser, Michael and Cooke Bailey, Jessica N and Nakazawa, Toru and Akiyama, Masato and Shiga, Yukihiro and Fuller, Zachary L and Wang, Xin and Hewitt, Alex W and Craig, Jamie E and Pasquale, Louis R and Mackey, David A and Wiggs, Janey L and Khawaja, Anthony P and Segr{\`e}, Ayellet V and 23andMe Research Team and International Glaucoma Genetics Consortium and Macgregor, Stuart}
}
@article {1664984,
	title = {NFκB-Mediated Expression of Phosphoinositide 3-Kinase δ Is Critical for Mesenchymal Transition in Retinal Pigment Epithelial Cells},
	journal = {Cells},
	volume = {12},
	number = {2},
	year = {2023},
	month = {2023 Jan 04},
	abstract = {Epithelial mesenchymal transition (EMT) plays a vital role in a variety of human diseases including proliferative vitreoretinopathy (PVR), in which retinal pigment epithelial (RPE) cells play a key part. Transcriptomic analysis showed that the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was up-regulated in human RPE cells upon treatment with transforming growth factor (TGF)-β2, a multifunctional cytokine associated with clinical PVR. Stimulation of human RPE cells with TGF-β2 induced expression of p110δ (the catalytic subunit of PI3Kδ) and activation of NFκB/p65. CRISPR-Cas9-mediated depletion of p110δ or NFκB/p65 suppressed TGF-β2-induced fibronectin expression and activation of Akt as well as migration of these cells. Intriguingly, abrogating expression of NFκB/p65 also blocked TGF-β2-induced expression of p110δ, and luciferase reporter assay indicated that TGF-β2 induced NFκB/p65 binding to the promoter of the PIK3CD that encodes p110δ. These data reveal that NFκB/p65-mediated expression of PI3Kδ is essential in human RPE cells for TGF-β2-induced EMT, uncovering hindrance of TGF-β2-induced expression of p110δ as a novel approach to inhibit PVR.},
	keywords = {Epithelial Cells, Humans, NF-kappa B, Phosphatidylinositol 3-Kinase, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Retinal Pigment Epithelium, Retinal Pigments, Transforming Growth Factor beta2, Vitreoretinopathy, Proliferative},
	issn = {2073-4409},
	doi = {10.3390/cells12020207},
	author = {Han, Haote and Yang, Yanhui and Han, Zhuo and Wang, Luping and Dong, Lijun and Qi, Hui and Liu, Bing and Tian, Jingkui and Vanhaesebroeck, Bart and Kazlauskas, Andrius and Zhang, Guoming and Zhang, Shaochong and Lei, Hetian}
}
@article {1470997,
	title = {Phosphoinositide 3-kinase δ inactivation prevents vitreous-induced activation of AKT/MDM2/p53 and migration of retinal pigment epithelial cells},
	journal = {J Biol Chem},
	volume = {294},
	number = {42},
	year = {2019},
	month = {2019 Oct 18},
	pages = {15408-15417},
	abstract = {Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that play a critical role in transmitting signals from cell-surface molecules to intracellular protein effectors. Key PI3Ks include PI3Kα, PI3Kβ, and PI3Kδ, which are regulated by receptors. The signaling pathway comprising the PI3Ks, along with a Ser/Thr kinase (AKT), a proto-oncogene product (mouse double minute (MDM)2), and a tumor suppressor protein (p53), plays an essential role in experimental proliferative vitreoretinopathy (PVR), which is a fibrotic blinding eye disorder. However, which PI3K isoforms are involved in PVR is unknown. A major characteristic of PVR is the formation of epi (or sub)-retinal membranes that consist of extracellular matrix and cells, including retinal pigment epithelium (RPE) cells, glial cells, and macrophages. RPE cells are considered key players in PVR pathogenesis. Using immunoblotting and immunofluorescence analyses, we herein provide the evidence that PI3Kδ is highly expressed in human RPEs when it is primarily expressed in leukocytes. We also found that PI3Kδ inactivation through two approaches, CRISPR/Cas9-mediated depletion and a PI3Kδ-specific inhibitor (idelalisib), not only blocks vitreous-induced activation of AKT and MDM2 but also abrogates a vitreous-stimulated decrease in p53. Furthermore, we demonstrate that PI3Kδ inactivation prevents vitreous-induced proliferation, migration, and contraction of human RPEs. These results suggest that PI3Kδ may represent a potential therapeutic target for RPE-related eye diseases, including PVR.},
	issn = {1083-351X},
	doi = {10.1074/jbc.RA119.010130},
	author = {Han, Haote and Chen, Na and Huang, Xionggao and Liu, Bing and Tian, Jingkui and Lei, Hetian}
}
@article {1452950,
	title = {A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration},
	journal = {Nat Commun},
	volume = {10},
	number = {1},
	year = {2019},
	month = {2019 Jul 26},
	pages = {3347},
	abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or "wet" form of AMD, no therapy is successful for the non-neovascular or "dry" form. Here we discuss the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments. In our view, these should emphasize system biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.},
	issn = {2041-1723},
	doi = {10.1038/s41467-019-11262-1},
	author = {Handa, James T and Bowes Rickman, Cathy and Dick, Andrew D and Gorin, Michael B and Miller, Joan W and Toth, Cynthia A and Ueffing, Marius and Zarbin, Marco and Farrer, Lindsay A}
}
@article {1354342,
	title = {Effect of retinopathy of prematurity on scotopic spatial summation},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {5},
	year = {2014},
	month = {2014 Apr 29},
	pages = {3311-3},
	abstract = {PURPOSE: To evaluate scotopic retinal organization in retinopathy of prematurity (ROP) through a study of spatial summation. METHODS: Thresholds for a range of stimulus diameters (0.4{\textdegree}-10{\textdegree}) were measured using a two alternative, spatial, forced choice psychophysical procedure. The critical diameter (DCRIT) for complete summation was estimated in subjects with a history of severe ROP (N = 7) and mild ROP (N = 17). Subjects who were born preterm and never had ROP (N = 16) and term-born subjects (N = 7) were also tested. The subjects ranged in age from 9 to 17 (median 13.5) years. RESULTS: Critical diameter for complete spatial summation was significantly larger in ROP subjects than in subjects who never had ROP and in term-born control subjects. Critical diameter varied significantly with severity of ROP. CONCLUSIONS: The larger DCRIT values in ROP are consistent with altered organization of the post receptor retina. This may offer the ROP retina a strategy for achieving noise reduction and good dark-adapted visual sensitivity.},
	keywords = {Adolescent, Child, Dark Adaptation, Female, Humans, Male, Photic Stimulation, Psychophysics, Retinal Rod Photoreceptor Cells, Retinopathy of Prematurity, Sensory Thresholds, Visual Perception},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14344},
	author = {Hansen, Ronald M and Tavormina, Jena L and Moskowitz, Anne and Fulton, Anne B}
}
@article {369056,
	title = {Temporal summation in children with a history of retinopathy of prematurity.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {2},
	year = {2015},
	month = {2015},
	pages = {914-7},
	abstract = {PURPOSE: To assess temporal summation in children with a history of retinopathy of prematurity (ROP) by determining the critical duration (tCRIT) for complete temporal summation under rod-mediated conditions. From prior ERG studies, it is known that the kinetics of activation of phototransduction are prolonged in the ROP rod photoreceptor. METHODS: Dark-adapted thresholds for detecting 10{\textdegree} diameter stimuli with durations from 10 to 640 ms were measured. A two-alternative, spatial, forced-choice psychophysical procedure was used. The tCRIT for complete summation was estimated in former preterm subjects with a history of severe ROP (n = 7), mild ROP (n = 23), and no ROP (n = 15). The subjects ranged in age from 10.4 to 17.6 (median 15.6) years. Age-similar term-born control subjects (n = 5) were also tested. RESULTS: Critical duration was significantly longer in subjects with a history of ROP than in subjects who never had ROP or who were born at term. Mean tCRIT in the mild ROP group [127.5 (SD = 19.9) ms] and severe group [147.6 (SD = 18.9) ms] did not differ significantly, but both were significantly longer than in former preterms who never had ROP [101.1 (SD = 16.5) ms] and in term-born controls [101.0 (SD = 19.5) ms]. CONCLUSIONS: In ROP subjects, tCRIT is significantly prolonged. This is likely due to abnormal kinetics in the rod outer segment.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-16102},
	author = {Hansen, Ronald M and Moskowitz, Anne and Tavormina, Jena L and Bush, Jennifer N and Soni, Garima and Fulton, Anne B}
}
@article {313156,
	title = {Imaging cone photoreceptor inner segments in the living human eye.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {4252},
	keywords = {Color Vision Defects, Female, Humans, Male, Ophthalmoscopy, Retinal Degeneration, Retinal Photoreceptor Cell Inner Segment, Retinitis Pigmentosa, Tomography, Optical Coherence},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14967},
	author = {Hansen, Ronald M}
}
@article {913466,
	title = {The neural retina in retinopathy of prematurity.},
	journal = {Prog Retin Eye Res},
	volume = {56},
	year = {2017},
	month = {2017 Jan},
	pages = {32-57},
	abstract = {Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2016.09.004},
	author = {Hansen, Ronald M and Moskowitz, Anne and Akula, James D and Fulton, Anne B}
}
@article {1589738,
	title = {Clinical Update on Metamorphopsia: Epidemiology, Diagnosis and Imaging},
	journal = {Curr Eye Res},
	volume = {46},
	number = {12},
	year = {2021},
	month = {2021 Dec},
	pages = {1777-1791},
	abstract = {Purpose: To discuss the pathophysiology of metamorphopsia, its characterisation using retinal imaging and methods of assessment of patient symptoms and visual function.Methods: A literature search of electronic databases was performedResults: Metamorphopsia has commonly been associated with vitreomacular interface disorders (such as epiretinal membrane) and has also regularly been noted in diseases of the retina and choroid, particularly age-related macular degeneration and central serous chorioretinopathy. Developments in optical coherence tomography retinal imaging have enabled improved imaging of the foveal microstructure and have led to the localisation of the pathophysiology of metamorphopsia within the retinal layers of the macula. Alteration of alignment of inner and outer retinal layers at various retinal loci has been identified using multimodal imaging in patients with metamorphopsia in a range of conditions. Although the Amsler Grid assessment of metamorphopsia is a useful clinical indicator, new emerging methods of metamorphopsia assessment with psychophysical tests such as M-CHARTS and preferential hyperacuity perimetry, have been developed.Conclusions: It appears that there is a complex relationship between visual acuity and metamorphopsia symptoms that vary between retinal conditions. Although metamorphopsia has traditionally been challenging to measure in the clinic, advances in technology promise more robust, easy-to-use tests. It is possible that home assessment of metamorphopsia, particularly in conditions such as age-related macular degeneration, may help to guide the need for further clinic evaluation and consideration of treatment.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2021.1912779},
	author = {Hanumunthadu, Daren and Lescrauwaet, Benedicte and Jaffe, Myles and Sadda, SriniVas and Wiecek, Emily and Hubschman, Jean Pierre and Patel, Praveen J}
}
@article {1603865,
	title = {Prospective study of dietary intake of branched-chain amino acids and the risk of primary open-angle glaucoma},
	journal = {Acta Ophthalmol},
	volume = {100},
	number = {3},
	year = {2022},
	month = {2022 May},
	pages = {e760-e769},
	abstract = {PURPOSE: Metabolomic and preclinical studies suggest that branched-chain amino acids (BCAA) may be inversely associated with neurodegenerative diseases including glaucoma. We therefore assessed the long-term association between dietary intake of BCAA and incident primary open-angle glaucoma (POAG) and POAG subtypes. METHODS: We followed biennially participants of the Nurses{\textquoteright} Health Study (NHS; 65 531 women: 1984-2016), Health Professionals Follow-up Study (42 254 men: 1986-2016) and NHSII (66 904 women; 1991-2017). Eligible participants were 40+ years old and reported eye examinations. Repeated validated food frequency questionnaires were used to assess dietary intake of BCAA. Incident cases of POAG and POAG subtypes defined by visual field (VF) loss and untreated intraocular pressure (IOP) were confirmed by medical record review. Multivariable-adjusted relative risks (MVRRs) and 95\% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: We identified 1946 incident POAG cases. The pooled MVRRs of POAG for the highest quintile (Q5 = 17.1 g/day) versus lowest quintile (Q1 = 11.2 g/day) of total BCAA intake was 0.93 (95\% CI, 0.73-1.19; ptrend  = 0.45; pheterogeneity by sex  = 0.24). For subtypes of POAG defined by IOP level or POAG with only peripheral VF loss, no associations were observed for men or women (ptrend  >= 0.20); however, for the POAG subtype with early paracentral VF loss, there was a suggestion of an inverse association in women (MVRRQ5versusQ1  = 0.80 [95\% CI, 0.57-1.12; ptrend  = 0.12]) but not in men (MVRRQ5versusQ1  = 1.38 [95\% CI, 0.81-2.34; ptrend  = 0.28; pheterogeneity by sex  = 0.06]). CONCLUSION: Higher dietary intake of BCAA was not associated with POAG risk.},
	keywords = {Adult, Amino Acids, Branched-Chain, Eating, Female, Follow-Up Studies, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Prospective Studies, Risk Factors, Scotoma, Surveys and Questionnaires, Vision Disorders},
	issn = {1755-3768},
	doi = {10.1111/aos.14971},
	author = {Hanyuda, Akiko and Rosner, Bernard A and Wiggs, Janey L and Willett, Walter C and Tsubota, Kazuo and Pasquale, Louis R and Kang, Jae H}
}
@article {1651374,
	title = {Long-Term Alcohol Consumption and Risk of Exfoliation Glaucoma/Glaucoma Suspect among US Health Professionals},
	journal = {Ophthalmology},
	year = {2022},
	author = {Hanyuda, A and Rosner, BA and Wiggs, J L and Negishi, K and Pasquale, L. R. and Kang, J H}
}
@article {1667712,
	title = {Long-term Alcohol Consumption and Risk of Exfoliation Glaucoma or Glaucoma Suspect Status among United States Health Professionals},
	journal = {Ophthalmology},
	volume = {130},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {187-197},
	abstract = {PURPOSE: To assess the association between intakes of total alcohol and individual alcoholic beverages and the incidence of exfoliation glaucoma/glaucoma suspect (XFG/XFGS) status. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 195 408 participants in the Nurses{\textquoteright} Health Study (1980-2018), the Health Professionals Follow-up Study (1986-2018), and the Nurses{\textquoteright} Health Study II (1991-2019) were followed biennially. Eligible participants at each 2-year risk period were ≧ 40 years and free of XFG/XFGS status with available data on diet and ophthalmic examination findings. METHODS: Cumulatively averaged total (primary exposure) and individual alcoholic beverage (beer, wine, and liquor) intakes from validated dietary information every 2-4 years. MAIN OUTCOME MEASURES: Confirmed incident XFG/XFGS status using medical records. We used per-eye Cox proportional hazards models, accounting for intereye correlations, to estimate multivariate-adjusted relative risks (MVRRs) and 95\% confidence intervals (CIs). RESULTS: During 6 877 823 eye-years of follow-up, 705 eyes with XFG/XFGS status were documented. Greater total alcohol consumption was associated significantly with higher XFG/XFGS status risk: the MVRR for XFG/XFGS status for cumulatively averaged alcohol consumption of ≧15 g/day or more versus nondrinking was 1.55 (95\% CI, 1.17-2.07; P\&nbsp;= 0.02 for trend). Long- and short-term alcohol intake was associated significantly with XFG/XFGS status risk, with the strongest associations with cumulatively averaged alcohol intake as of 4 years before diagnosis (MVRR >= 15 g/day vs. nondrinking, 1.65; 95\% CI, 1.25-2.18; P\&nbsp;= 0.002 for trend). Compared with nondrinkers, consuming ≧ 3.6 drinks of beer, wine, or liquor per week was associated with the following MVRRs for XFG/XFGS status: 1.26 (95\% CI, 0.89-1.77; P\&nbsp;= 0.40 for trend), 1.30 (95\% CI, 1.00-1.68; P\&nbsp;= 0.15 for trend), and 1.46 (95\% CI, 1.15-1.85; P\&nbsp;= 0.01 for trend), respectively. We did not observe interactions by age, latitude, residential tier, or intakes of folate or vitamin A (P \&gt; 0.40 for interaction); however, the association between alcohol and XFG/XFGS status was suggestively stronger for those without a family history of glaucoma (P\&nbsp;= 0.10 for interaction). CONCLUSIONS: Long-term alcohol consumption was associated with a higher risk of XFG/XFGS status. Our findings provide further clues regarding the XFG/XFGS etiology.},
	keywords = {Alcohol Drinking, Exfoliation Syndrome, Follow-Up Studies, Glaucoma, Humans, Ocular Hypertension, Prospective Studies, Risk Factors, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.08.023},
	author = {Hanyuda, Akiko and Rosner, Bernard A and Wiggs, Janey L and Negishi, Kazuno and Pasquale, Louis R and Kang, Jae H}
}
@article {1498260,
	title = {Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: data from three US cohorts},
	journal = {Eye (Lond)},
	volume = {34},
	number = {8},
	year = {2020},
	month = {2020 Aug},
	pages = {1465-1475},
	abstract = {BACKGROUND/OBJECTIVES: To assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis. SUBJECTS/METHODS: We followed 185,638 participants of three large US prospective cohorts biennially (1976-2016, 1986-2016 and 1991-2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95\% confidence intervals (CIs). RESULTS: There was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95\% CI, 0.91-1.39; P = 0.40) for the overall score; 1.10 (95\% CI, 0.89-1.35; P = 0.38) for the animal score and 0.96 (95\% CI, 0.79-1.18; P = 0.88) for the vegetable score. No differential associations by IOP level was found (P >= 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95\% CI, 0.55-1.10]; P = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95\% CI, 0.83-1.44]; P = 0.14; P = 0.03). CONCLUSIONS: Low-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss.},
	issn = {1476-5454},
	doi = {10.1038/s41433-020-0820-5},
	author = {Hanyuda, Akiko and Rosner, Bernard A and Wiggs, Janey L and Willett, Walter C and Tsubota, Kazuo and Pasquale, Louis R and Kang, Jae H}
}
@article {1435402,
	title = {Stem cell-derived tissue-associated regulatory T cells suppress the activity of pathogenic cells in autoimmune diabetes},
	journal = {JCI Insight},
	volume = {4},
	number = {7},
	year = {2019},
	month = {2019 Apr 04},
	abstract = {The autoantigen-specific Tregs from pluripotent stem cells (PSCs), i.e., PSC-Tregs, have the ability to suppress autoimmunity. PSC-Tregs can be programmed to be tissue associated and to infiltrate into local inflamed tissues to suppress autoimmune responses after adoptive transfer. Nevertheless, the mechanisms by which the autoantigen-specific PSC-Tregs suppress the autoimmune response remain to be fully elucidated. In this study, we generated functional autoantigen-specific Tregs from the induced PSC (iPSCs), i.e., iPSC-Tregs, and investigated the underlying mechanisms of autoimmunity suppression by these Tregs in a type 1 diabetes (T1D) murine model. A double-Tg mouse model of T1D was established in F1 mice, in which the first generation of RIP-mOVA Tg mice that were crossed with OT-I T cell receptor (TCR) Tg mice was challenged with vaccinia viruses expressing OVA (VACV-OVA). We show that adoptive transfer of OVA-specific iPSC-Tregs greatly suppressed autoimmunity in the animal model and prevented the insulin-secreting pancreatic β cells from destruction. Further, we demonstrate that the adoptive transfer significantly reduced the expression of ICAM-1 in the diabetic pancreas and inhibited the migration of pathogenic CD8+ T cells and the production of the proinflammatory IFN-γ in the pancreas. These results indicate that the stem cell-derived tissue-associated Tregs can robustly accumulate in the diabetic pancreas, and, through downregulating the expression of ICAM-1 in the local inflamed tissues and inhibiting the production of proinflammatory cytokine IFN-γ, suppress the migration and activity of the pathogenic immune cells that cause T1D.},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.126471},
	author = {Haque, Mohammad and Lei, Fengyang and Xiong, Xiaofang and Das, Jugal Kishore and Ren, Xingcong and Fang, Deyu and Salek-Ardakani, Shahram and Yang, Jin-Ming and Song, Jianxun}
}
@article {1522742,
	title = {Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺},
	journal = {iScience},
	volume = {23},
	number = {7},
	year = {2020},
	month = {2020 Jul 24},
	pages = {101333},
	abstract = {The viral antigen (Ag)-specific CD8 cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress hepatitis B virus (HBV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the liver to suppress HBV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs provoke the antiviral response remain to be fully elucidated. In this study, we generated the functional HBV surface Ag-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the underlying mechanisms of the CTL-mediated antiviral replication in a murine model. We show that adoptive transfer of HBV surface Ag-specific iPSC-CTLs greatly suppressed HBV replication and prevented HBV surface Ag expression. We further demonstrate that the adoptive transfer significantly increased T\&nbsp;cell accumulation and production of antiviral cytokines. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the liver and suppress HBV replication through producing antiviral cytokines.},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2020.101333},
	author = {Haque, Mohammad and Lei, Fengyang and Xiong, Xiaofang and Ren, Yijie and Kumar, Anil and Das, Jugal Kishore and Ren, Xingcong and Fang, Deyu and de Figueiredo, Paul and Yang, Jin-Ming and Song, Jianxun}
}
@article {1573104,
	title = {An optimized protocol for the generation of HBV viral antigen-specific T lymphocytes from pluripotent stem cells},
	journal = {STAR Protoc},
	volume = {2},
	number = {1},
	year = {2021},
	month = {2021 Mar 19},
	pages = {100264},
	abstract = {In T\&nbsp;cell-based cancer immunotherapy, tumor antigen (Ag)-specific CD8 cytotoxic T lymphocytes (CTLs) can specifically target tumor Ags on malignant cells. This promising approach drove us to adopt this strategy of T\&nbsp;cell transfer (ACT)-based immunotherapy for chronic viral infections. Here, we describe the generation of hepatitis B virus (HBV) Ag-specific CTLs from induced pluripotent stem cells (iPSCs), i.e., iPSC-CTLs. Ag-specific iPSC-CTLs can target HBV Ag cells and infiltrate into the liver to suppress HBV replication in a murine model. For complete details on the use and execution of this protocol, please refer to Haque et\&nbsp;al. (2020).},
	issn = {2666-1667},
	doi = {10.1016/j.xpro.2020.100264},
	author = {Haque, Mohammad and Xiong, Xiaofang and Lei, Fengyang and Das, Jugal Kishore and Song, Jianxun}
}
@article {1589741,
	title = {Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells},
	journal = {Viruses},
	volume = {13},
	number = {5},
	year = {2021},
	month = {2021 Apr 25},
	abstract = {The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress the human immunodeficiency virus (HIV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the local tissues to suppress HIV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs elicit the antiviral response remain to be fully elucidated. In this study, we generated the functional HIV-1 Gag epitope SL9-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the suppression of SL9-specific iPSC-CTLs on viral replication and the protection of CD4+ T cells. A chimeric HIV-1, i.e., EcoHIV, was used to produce HIV replication in mice. We show that adoptive transfer of SL9-specific iPSC-CTLs greatly suppressed EcoHIV replication in the peritoneal macrophages and spleen in the animal model. Furthermore, we demonstrate that the adoptive transfer significantly reduced expression of PD-1 on CD4+ T cells in the spleen and generated persistent anti-HIV memory T cells. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the local tissues to suppress HIV replication and prevent CD4+ T cell exhaustion through reduction of PD-1 expression.},
	issn = {1999-4915},
	doi = {10.3390/v13050753},
	author = {Haque, Mohammad and Lei, Fengyang and Xiong, Xiaofang and Ren, Yijie and Peng, Hao-Yun and Wang, Liqing and Kumar, Anil and Das, Jugal Kishore and Song, Jianxun}
}
@article {1402576,
	title = {Review shows that donor milk does not promote the growth and development of preterm infants as well as maternal milk},
	journal = {Acta Paediatr},
	volume = {108},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {998-1007},
	abstract = {AIM: This nonsystematic review examined differences in the composition of raw maternal breastmilk and pasteurised donor milk and possible health effects on preterm infants. METHODS: We searched PubMed up to July 2018 for studies published in English that focused on four comparisons as follows: raw maternal milk versus donor milk, human milk before and after Holder pasteurisation, milk from mothers who delivered preterm and at term and milk collected during early and late lactation. We also searched for possible effects of the milk components, as well as the effects of maternal and donor milk on preterm infants{\textquoteright} health. RESULTS: Raw maternal milk contained factors involved in antioxidant and anti-inflammatory defence, gut microbiome establishment and the maturation of immune defences, food tolerability and metabolism. Many of these factors were reduced or abolished in processed donor milk. Both maternal milk and donor milk have been associated with a reduced incidence of necrotising enterocolitis. High-dose feeding with maternal milk during the neonatal period reportedly reduced the risk of other morbidities and promoted growth and neurodevelopment. CONCLUSION: Many of the components in raw maternal breastmilk were lacking in pasteurised donor milk, which was inferior in promoting the growth and development of very preterm infants.},
	issn = {1651-2227},
	doi = {10.1111/apa.14702},
	author = {H{\r a}rd, Anna-Lena and Nilsson, Anders K and Lund, Anna-My and Hansen-Pupp, Ingrid and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1664969,
	title = {Manhattan Vision Screening and Follow-up Study (NYC-SIGHT): Baseline Results and Costs of a Cluster-Randomized Trial},
	journal = {Am J Ophthalmol},
	year = {2023},
	month = {2023 Jan 20},
	abstract = {PURPOSE: To describe the 15-month baseline results and costs of the Manhattan Vision Screening and Follow-up Study, which aims to investigate whether innovative community-based eye health screening can improve early detection and management of glaucoma and other eye diseases among high-risk populations. DESIGN: 5-year prospective, cluster-randomized controlled trial. METHODS: Individuals age 40+ were recruited from public housing buildings in New York City for an eye health screening (visual acuity (VA) with correction, intraocular pressure measurements (IOP), and fundus photography). Participants with VA 20/40 or worse, IOP 23-29 mmHg, or an unreadable fundus image failed the screening and were scheduled for an optometric exam at the same location; those with an abnormal image were referred to ophthalmology. A cost analysis was conducted alongside the study. RESULTS: 708 participants were screened; mean age 68.6{\textpm}11.9 years, female (65.1\%), African American (51.8\%) and Hispanic (42\%). 78.4\% (n = 555) failed the eye health screening; 35\% (n= 250) had an abnormal image and were also referred to ophthalmology. 308 participants attended the optometric exam; 218 were referred to ophthalmology. Overall, 66.1\% were referred to ophthalmology. The cost per participant to deliver the eye health screening and optometric exam was $180.88. The cost per case of eye disease detected was $273.64. CONCLUSIONS: This innovative study in public housing developments targeted high-risk populations, provided access to eye-care, and improved early detection of ocular diseases in New York City. The study has identified strategies to overcoming barriers to eye care to reduce eye health disparities.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.01.019},
	author = {Hark, Lisa A and Horowitz, Jason D and Gorroochurn, Prakash and Park, Lisa and Wang, Qing and Diamond, Daniel F and Harizman, Noga and Auran, James D and Maruri, Stefania C and Henriquez, Desiree R and Carrion, Jailine and Muhire, Remy S Manzi and Kresch, Yocheved S and Pizzi, Laura T and Jutkowitz, Eric and Sapru, Saloni and Sharma, Tarun and De Moraes, C Gustavo and Friedman, David S and Liebmann, Jeffrey M and Cioffi, George A}
}
@article {1773486,
	title = {Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT): Subanalysis of Referral to Ophthalmology},
	journal = {Curr Eye Res},
	volume = {49},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {197-206},
	abstract = {PURPOSE: The Manhattan Vision Screening and Follow-up Study aims to provide access to eye care for underserved populations, detect native rates of ocular pathology, and refer participants with eye disease to ophthalmology. This subanalysis describes the reasons for referral to ophthalmology and identifies risk factors associated with being referred. METHODS: Enrolled participants were aged >=40 years, living independently in public housing developments and able to provide consent for eye health screenings. Those with habitual visual acuity 20/40 or worse, intraocular pressure (IOP) 23-29 mmHg, or an unreadable fundus image failed and were scheduled with the on-site optometrist. The optometric exam determined whether further referral to ophthalmology for a clinic exam was warranted. Those with an abnormal image or IOP >=30 mmHg were referred directly to ophthalmology. Main outcome was factors associated with referral to ophthalmology. RESULTS: A total of 708 individuals completed the eye health screening over 15 months. A total of 468 participants were referred to ophthalmology (250 had an abnormal image and 218 were referred by the optometrist). Those referred were predominantly older adults (mean age 70.0 {\textpm} 11.4 years), female (66.7\%), African American (55.1\%) and Hispanic (39.5\%). Seventy percent of participants had not had a recent eye exam. Stepwise multivariate logistic regression analysis showed that participants with pre-existing glaucoma (OR 3.14, 95\% CI 1.62 to 6.08, p = 0.001), an IOP >=23 mmHg (OR 5.04, 95\% 1.91 to 13.28, p = 0.001), or vision impairment (mild) (OR 2.51, 95\% CI 1.68 to 3.77, p = 0.001) had significantly higher odds of being referred to ophthalmology. CONCLUSION: This targeted community-based study in Upper Manhattan provided access to eye care and detected a significant amount of ocular pathology requiring referral to ophthalmology in this high-risk population.},
	keywords = {Aged, Aged, 80 and over, Female, Follow-Up Studies, Glaucoma, Humans, Intraocular Pressure, Middle Aged, Ophthalmology, Referral and Consultation, Vision Screening},
	issn = {1460-2202},
	doi = {10.1080/02713683.2023.2269614},
	author = {Hark, Lisa A and Lin, Weijie Violet and Hirji, Sitara and Gorroochurn, Prakash and Horowitz, Jason D and Diamond, Daniel F and Park, Lisa and Wang, Qing and Auran, James D and Maruri, Stefania C and Henriquez, Desiree R and Sharma, Tarun and Valenzuela, Ives and Liebmann, Jeffrey M and Cioffi, George A and Friedman, David S and Harizman, Noga}
}
@article {1359930,
	title = {Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Analysis of Unreadable Fundus Images},
	journal = {J Glaucoma},
	volume = {27},
	number = {11},
	year = {2018},
	month = {2018 Nov},
	pages = {999-1008},
	abstract = {PURPOSE: The purpose of this study was to ascertain determinants of unreadable fundus images for participants enrolled in the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study. METHODS: Individuals were screened for glaucoma at 7 primary care practices and 4 Federally Qualified Health Centers using telemedicine. Screening (visit 1) included fundus photography, assessing family history of glaucoma, and intraocular pressure (IOP) measurements. Participants with an unreadable image in at least one eye were deemed unreadable and invited to return for a confirmatory eye examination (visit 2). RESULTS: A total of 906 participants completed the visit 1 eye screening and 17.1\% (n=155/906) were "unreadable." In the multivariable logistic regression analysis, older age, male sex, smoking, and worse visual acuity were significantly associated with an unreadable fundus image finding at the eye screening (P\&lt;0.05). Of the 89 participants who were invited for the confirmatory eye examination solely for unreadable images and attended visit 2, 58 (65.2\%) were diagnosed with at least one ocular pathology. The most frequent diagnoses were cataracts (n=71; 15 visually significant, 56 nonvisually significant), glaucoma suspects (n=27), and anatomical narrow angle (n=10). CONCLUSIONS: Understanding the causes of unreadable fundus images will foster improvements in telemedicine techniques to optimize the predictive accuracy, efficiency, and cost in ophthalmology. A high proportion of participants with unreadable images (65.2\%) in our study were diagnosed with some ocular pathology, indicating that the finding of an unreadable fundus image warrants a referral for a comprehensive follow-up eye examination.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001082},
	author = {Hark, Lisa A and Myers, Jonathan S and Rahmatnejad, Kamran and Wang, Qianqian and Zhan, Tingting and Hegarty, Sarah E and Leiby, Benjamin E and Udyaver, Sanika and Waisbourd, Michael and Leite, Stela and Henderer, Jeffrey D and Pasquale, Louis R and Lee, Paul P and Haller, Julia A and Katz, L Jay}
}
@article {1179221,
	title = {Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Methods and Screening Results},
	journal = {Am J Ophthalmol},
	volume = {181},
	year = {2017},
	month = {2017 Sep},
	pages = {114-124},
	abstract = {PURPOSE: To describe methodology and screening results from the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study. DESIGN: Screening program results for a prospective randomized clinical trial. METHODS: Individuals were recruited who were African-American, Hispanic/Latino, or Asian over age 40 years; white individuals over age 65 years; and any ethnicity over age 40 years with a family history of glaucoma or diabetes. Primary care offices and Federally Qualified Health Centers were used for telemedicine (Visit 1). Two posterior fundus photographs and 1 anterior segment photograph were captured per eye in each participant, using a nonmydriatic, autofocus, hand-held fundus camera (Volk Optical, Mentor, Ohio, USA). Medical and ocular history, family history of glaucoma, visual acuity, and intraocular pressure measurements using the ICare rebound tonometer (ICare, Helsinki, Finland) were obtained. Images were read remotely by a trained retina reader and a glaucoma specialist. RESULTS: From April 1, 2015, to February 6, 2017, 906 individuals consented and attended Visit 1. Of these, 553 participants were female (61.0\%) and 550 were African-American (60.7\%), with a mean age of 58.7 years. A total of 532 (58.7\%) participants had diabetes, and 616 (68\%) had a history of hypertension. During Visit 1, 356 (39.3\%) participants were graded with a normal image. Using image data from the worse eye, 333 (36.8\%) were abnormal and 155 (17.1\%) were unreadable. A total of 258 (28.5\%) had a suspicious nerve, 62 (6.8\%) had ocular hypertension, 102 (11.3\%) had diabetic retinopathy, and 68 (7.5\%) had other retinal abnormalities. CONCLUSION: An integrated telemedicine screening intervention in primary care offices and Federally Qualified Health Centers detected high rate of suspicious optic nerves, ocular hypertension, and retinal pathology.},
	keywords = {Adult, Aged, Aged, 80 and over, Blood Pressure, Body Mass Index, Community Health Services, Diagnostic Techniques, Ophthalmological, Female, Follow-Up Studies, Glaucoma, Open-Angle, Hemoglobin A, Glycosylated, Humans, Intraocular Pressure, Male, Middle Aged, Ocular Hypertension, Optic Nerve Diseases, Philadelphia, Physicians, Primary Care, Prospective Studies, Telemedicine, Tonometry, Ocular, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.06.024},
	author = {Hark, Lisa A and Katz, L Jay and Myers, Jonathan S and Waisbourd, Michael and Johnson, Deiana and Pizzi, Laura T and Leiby, Benjamin E and Fudemberg, Scott J and Mantravadi, Anand V and Henderer, Jeffrey D and Zhan, Tingting and Molineaux, Jeanne and Doyle, Vance and Divers, Meskerem and Burns, Christine and Murchison, Ann P and Reber, Shae and Resende, Arthur and Bui, Thien Dan V and Lee, Jane and Crews, John E and Saaddine, Jinan B and Lee, Paul P and Pasquale, Louis R and Haller, Julia A}
}
@article {1773516,
	title = {Postnatal hyperglycemia alters amino acid profile in retinas (model of Phase I ROP)},
	journal = {iScience},
	volume = {26},
	number = {10},
	year = {2023},
	month = {2023 Oct 20},
	pages = {108021},
	abstract = {Nutritional deprivation occurring in most preterm infants postnatally can induce hyperglycemia, a significant and independent risk factor for suppressing physiological retinal vascularization (Phase I retinopathy of prematurity (ROP)), leading to compensatory but pathological neovascularization. Amino acid supplementation reduces retinal neovascularization in mice. Little is known about amino acid contribution to Phase I ROP. In mice modeling hyperglycemia-associated Phase I ROP, we found significant changes in retinal amino acids (including most decreased L-leucine, L-isoleucine, and L-valine). Parenteral L-isoleucine suppressed physiological retinal vascularization. In premature infants, severe ROP was associated with a higher mean intake of parenteral versus enteral amino acids in the first two weeks of life after adjustment for treatment group, gestational age at birth, birth weight, and sex. The number of days with parenteral amino acids support independently predicted severe ROP. Further understanding and modulating amino acids may help improve nutritional intervention and prevent Phase I ROP.},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2023.108021},
	author = {Harman, Jarrod C and Pivodic, Aldina and Nilsson, Anders K and Boeck, Myriam and Yagi, Hitomi and Neilsen, Katherine and Ko, Minji and Yang, Jay and Kinter, Michael and Hellstr{\"o}m, Ann and Fu, Zhongjie}
}
@article {1323925,
	title = {Diffusion-Weighted Imaging Changes in a Child With Posterior Ischemic Optic Neuropathy},
	journal = {Pediatr Neurol},
	volume = {84},
	year = {2018},
	month = {2018 Jul},
	pages = {49-52},
	abstract = {BACKGROUND: Posterior ischemic optic neuropathy results from ischemia of the retrobulbar aspect of the optic nerve. It presents as acute loss of vision without optic disc swelling. This is rare in children, with only seven cases reported to date. Neuroimaging is frequently used to aid in the diagnosis of acute visual complaints in children; however, none of the cases described to date delineate the neuroimaging findings of this entity in children. METHODS: We retrospectively reviewed the electronic medical record. RESULTS: We describe the MRI findings in a 10-month-old boy with posterior ischemic optic neuropathy after intraophthalmic artery injection of chemotherapy for retinoblastoma. CONCLUSIONS: As targeted therapies for retinoblastoma and other diseases amenable to intravascular treatment delivery are more frequently used, the risk of grave vision-related side effects increases. Posterior ischemic optic neuropathy should be considered in the differential diagnosis of any child presenting with acute loss of vision. Dedicated imaging of the orbits can elucidate specific findings that may aid in the diagnosis of this entity in children.},
	issn = {1873-5150},
	doi = {10.1016/j.pediatrneurol.2018.03.014},
	author = {Harrar, Dana B and Solomon, Jessica and Shah, Ankoor S and Vaughn, Jennifer and Durbin, Adam D and Rivkin, Michael J}
}
@article {1328883,
	title = {A Novel Murine Model of Radiation Keratopathy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {10},
	year = {2018},
	month = {2018 Aug 01},
	pages = {3889-3896},
	abstract = {Purpose: Radiation therapy results in severe chronic keratopathy and dry eye disease. We developed a novel mouse model for radiation keratopathy to allow future mechanistic studies. Methods: Six to 8-week-old BALB/c mice underwent sublethal irradiation to the head only from a Cesium-137 irradiator, 2 {\texttimes} 550 rad, 3-hours apart. Irradiated mice were clinically evaluated by corneal fluorescein staining (CFS) at 1, 2, and 3 months, after which corneas were excised and immunofluorescence histochemistry performed with anti-CD45, anti-MHC class II, and anti-β-tubulin antibodies. Results: The survival rate after irradiation was 100\%. Mice demonstrated significant CFS and hair loss around the eyes. Corneal nerve density decreased in the central and peripheral corneas (P \&lt; 0.01) at 2 and 3 months, respectively. CD45+ immune cell densities increased in the central and peripheral corneas (P \&lt; 0.005, P \&lt; 0.001) at 2 and 3 months, respectively. MHC class II, a sign of antigen presenting cell activation, significantly increased after irradiation in the central and peripheral corneas at 2 and 3 months (P = 0.02). A strong inverse correlation was noted between decreased corneal nerves and increase in CD45+ cells in the central cornea at 2 (P = 0.04, r = -0.89) and 3 months (P = 0.03, r = -0.91) after irradiation. Conclusions: We present a model of radiation keratopathy and demonstrate significant nerve loss and increase in immune cell influx and activation within months. This model will enable future investigations to understand the effects of radiation therapy on the eye, and to study mechanisms of neuro-immune crosstalk in the cornea.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-24567},
	author = {Harris, Deshea L and Yamaguchi, Takefumi and Hamrah, Pedram}
}
@article {1532363,
	title = {Post-operative intracranial gas migration with optic nerve infiltration and atrophy following retinal detachment repair},
	journal = {Am J Ophthalmol Case Rep},
	volume = {20},
	year = {2020},
	month = {2020 Dec},
	pages = {100920},
	abstract = {Purpose: To report a patient with post-operative gas migration into the optic nerve and lateral ventricles after retinal detachment repair. Observations: A 78-year-old pseudophakic man developed a temporal visual field cut in his non-operative, right eye 3 weeks after repair of a recurrent, shallow, macula-involving retinal detachment with perfluoropropane intraocular gas in the left eye. Visual acuity in the right eye measured 20/40, and static perimetry demonstrated temporal visual field loss that respected the vertical midline. Dilated fundus examination of the right eye was unrevealing for any retinal cause, raising suspicion for an intracranial etiology. An urgent CT scan of the brain demonstrated gas in all segments of the left optic nerve and lateral ventricles, consistent with intracranial gas migration along the optic nerve. Given the absence of systemic neurologic symptoms, cautious observation was advised on consultation with neuroradiology and neurosurgery, and follow-up CT scan 1 week later showed resolution of the intracranial gas. By 10-weeks post-operatively, vision returned to 20/20 in the right eye with persistent temporal field loss, and the left eye was hand motions (20/70 pre-operatively) with evidence of optic nerve atrophy and severe cupping. Conclusions: Intracranial gas migration is a rare complication of retinaldetachment repair with intraocular gas and may occur in the setting of structural defects of the optic nerve and high post-operative intraocular pressure. Clinicians should be alert to this rare but serious complication, which can cause neurologic symptoms and result in vision loss in both the operative and non-operative eyes.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2020.100920},
	author = {Harris, James M and Han, Ian C and Sachdeva, Mira M and Zhang, Alice Y and Zebardast, Nazlee}
}
@article {1661851,
	title = {The Eyes Have It: How Critical are Ophthalmic Findings to the Diagnosis of Pediatric Abusive Head Trauma?},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {3-8},
	abstract = {Pediatric abusive head trauma (AHT), still colloquially known as shaken baby syndrome, is a leading cause of morbidity and mortality among infants. Controversy has grown surrounding this diagnosis, and the specificity of the clinical findings-subdural hemorrhage, cerebral edema, and retinal hemorrhages-has been challenged. A literature search of peer reviewed publications on PubMed pertaining to the history, clinical, and pathologic features of AHT was conducted using the terms "shaken baby syndrome," "non-accidental trauma," "abusive head trauma," "inflicted traumatic brain injury," "shaken impact syndrome," and "whiplash shaken infant syndrome." Focus was placed on articles discussing ophthalmic findings in AHT. Retinal hemorrhages-particularly those that are too numerous to count, occurring in all layers of the retina (preretinal, intraretinal, subretinal), covering the peripheral pole and extending to the ora serrata, and accompanied by retinoschisis and other ocular/periocular hemorrhages-are highly suggestive of AHT, particularly in the absence of otherwise explained massive accidental trauma. Although the diagnosis has grown in controversy in recent years, AHT has well-documented clinical and pathologic findings across a large number of studies.},
	keywords = {Child, Child abuse, Craniocerebral Trauma, Humans, Infant, Retina, Retinal Hemorrhage, Shaken Baby Syndrome},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152712},
	author = {Harris, Cynthia K and Stagner, Anna M}
}
@article {1653607,
	title = {Pseudomonas species may appear strikingly filamentous in tissue sections: an important consideration for surgical pathologists and a reminder of the utility of modified silver impregnation methods},
	journal = {Histopathology},
	volume = {82},
	number = {2},
	year = {2023},
	month = {2023 Jan},
	pages = {359-364},
	abstract = {Although tissue culture is the gold standard for diagnosing infection, histologic examination of surgically resected tissue can be a critical component in the diagnosis of tissue infection. The goal of this brief report is to alert surgical pathologists that Pseudomonas species can appear strikingly filamentous histologically and may somewhat mimic the appearance of filamentous bacteria, such Actinomyces or Nocardia, or thin fungal hyphae. A secondary aim is to raise awareness that Pseudomonas can sometimes only be identified histologically through the use of a modified silver impregnation method (Steiner stain). Five cases of filamentous Pseudomonas were encountered in three different surgical pathology subspecialities (ophthalmic pathology, cardiovascular pathology, and dermatopathology) over a 1-year period. All cases were of formalin-fixed, paraffin-embedded tissue, stained using hematoxylin \&amp; eosin (H\&amp;E) and multiple histochemical stains. Four cases grew Pseudomonas aeruginosa in culture and, in the fifth case, a nonaeruginosa species was detected using polymerase chain reaction-based methods. The markedly filamentous-appearing Pseudomonas organisms were identified in five different tissue sites: vascular graft, enucleation (whole eye) specimen, scleral biopsy, soft-tissue excision, and skin punch biopsy. In one of the five cases the organisms were seen on H\&amp;E, and in only two of the five were the organisms seen on Brown-Hopps stain. In all five cases, the organisms were identified on Steiner stain. It is therefore important to recognize that Pseudomonas can appear markedly filamentous, Pseudomonas or other bacterial infection is suspected, the surgical pathologist would be advised to employ the Steiner stain to most consistently detect the organisms.},
	keywords = {Humans, Pseudomonas, Silver},
	issn = {1365-2559},
	doi = {10.1111/his.14811},
	author = {Harris, Cynthia K and Christensen, Bianca B and Kwan, Melanie and Foreman, Ruth K and Stagner, Anna M}
}
@article {1354343,
	title = {Integrating retinotopic features in spatiotopic coordinates},
	journal = {J Neurosci},
	volume = {34},
	number = {21},
	year = {2014},
	month = {2014 May 21},
	pages = {7351-60},
	abstract = {The receptive fields of early visual neurons are anchored in retinotopic coordinates (Hubel and Wiesel, 1962). Eye movements shift these receptive fields and therefore require that different populations of neurons encode an object{\textquoteright}s constituent features across saccades. Whether feature groupings are preserved across successive fixations or processing starts anew with each fixation has been hotly debated (Melcher and Morrone, 2003; Melcher, 2005, 2010; Knapen et al., 2009; Cavanagh et al., 2010a,b; Morris et al., 2010). Here we show that feature integration initially occurs within retinotopic coordinates, but is then conserved within a spatiotopic coordinate frame independent of where the features fall on the retinas. With human observers, we first found that the relative timing of visual features plays a critical role in determining the spatial area over which features are grouped. We exploited this temporal dependence of feature integration to show that features co-occurring within 45 ms remain grouped across eye movements. Our results thus challenge purely feedforward models of feature integration (Pelli, 2008; Freeman and Simoncelli, 2011) that begin de novo after every eye movement, and implicate the involvement of brain areas beyond early visual cortex. The strong temporal dependence we quantify and its link with trans-saccadic object perception instead suggest that feature integration depends, at least in part, on feedback from higher brain areas (Mumford, 1992; Rao and Ballard, 1999; Di Lollo et al., 2000; Moore and Armstrong, 2003; Stanford et al., 2010).},
	keywords = {Attention, Humans, Motion Perception, Photic Stimulation, Retina, Saccades, Space Perception, Time Factors, Visual Fields, Visual Pathways},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.5252-13.2014},
	author = {Harrison, William J and Bex, Peter J}
}
@article {987966,
	title = {Patching retinal breaks with Seprafilm for treating retinal detachments in humans: 9 years of follow-up},
	journal = {Eye (Lond)},
	volume = {31},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {776-780},
	abstract = {PurposeTo describe the long-term surgical outcomes of four patients treated for retinal detachment using Seprafilm as a novel technique.MethodsRetinal breaks in four eyes were covered with Seprafilm using a transvitreal approach after cataract surgery, pars plana vitrectomy, fluid-air exchange, and laser photocoagulation. Neither long-standing gas nor silicone oil was used. The patients were not instructed to maintain a specific head positioning postoperatively.ResultsSuccessful retinal reattachment was achieved with a single surgery in all four eyes, and none developed proliferative vitreoretinopathy. The mean best-corrected visual acuity preoperatively and 9 years postoperatively were 20/97 and 20/33, respectively. The intraocular pressure increased several days postoperatively that lasted no longer than 2 weeks. Visual field defects either in the inferonasal or inferotemporal quadrant were detected postoperatively. The mean electroretinogram a- and b-wave amplitude ratios of the operated eyes to the fellow eyes were 0.68 and 0.64 preoperatively and 0.87 and 0.92 postoperatively, respectively. The mean corneal endothelial cell density was 2365 cells/mm(2) preoperatively and 2592 cells/mm(2) postoperatively.ConclusionCovering retinal breaks with Seprafilm may promote retinal reattachment without gas tamponade and postoperative head positioning. The visual outcomes 9 years postoperatively showed no apparent adverse effects of intraocular application of Seprafilm.},
	issn = {1476-5454},
	doi = {10.1038/eye.2016.329},
	author = {Haruta, M and Arai, M and Sueda, J. and Hirose, T. and Yamakawa, R}
}
@article {541276,
	title = {Wide Dispersion and Diversity of Clonally Related Inhibitory Interneurons.},
	journal = {Neuron},
	volume = {87},
	number = {5},
	year = {2015},
	month = {2015 Sep 2},
	pages = {999-1007},
	abstract = {The mammalian neocortex is composed of two major neuronal cell types with distinct origins: excitatory pyramidal neurons and inhibitory interneurons, generated in dorsal and ventral progenitor zones of the embryonic telencephalon, respectively. Thus, inhibitory neurons migrate relatively long distances to reach their destination in the developing forebrain. The role of lineage in the organization and circuitry of interneurons is still not well understood. Utilizing a combination of genetics, retroviral fate mapping, and lineage-specific retroviral barcode labeling, we\&nbsp;find that clonally related interneurons can be widely dispersed while unrelated interneurons can be closely clustered. These data suggest that migratory mechanisms related to the clustering of interneurons occur largely independent of their clonal origin.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2015.07.030},
	author = {Harwell, Corey C and Fuentealba, Luis C and Gonzalez-Cerrillo, Adrian and Parker, Phillip R L and Gertz, Caitlyn C and Mazzola, Emanuele and Garcia, Miguel Turrero and Alvarez-Buylla, Arturo and Cepko, Constance L and Kriegstein, Arnold R}
}
@article {1658672,
	title = {Ocular involvement in Mycoplasma induced rash and mucositis: A systematic review of the literature},
	journal = {Ocul Surf},
	year = {2022},
	month = {2022 Nov 14},
	abstract = {Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2022.11.007},
	author = {Haseeb, Abid and Elhusseiny, Abdelrahman M and ElSheikh, Reem H and Tahboub, Mohammad A and Kwan, James T and Saeed, Hajirah N}
}
@article {1154931,
	title = {Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	number = {36},
	year = {2017},
	month = {2017 Sep 05},
	pages = {E7545-E7553},
	abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1620898114},
	author = {Hasegawa, Eiichi and Inafuku, Saori and Mulki, Lama and Okunuki, Yoko and Yanai, Ryoji and Smith, Kaylee E and Kim, Clifford B and Klokman, Garrett and Bielenberg, Diane R and Puli, Narender and Falck, John R and Husain, Deeba and Miller, Joan W and Edin, Matthew L and Zeldin, Darryl C and Stephen Lee, Kin Sing and Hammock, Bruce D and Schunck, Wolf-Hagen and Connor, Kip M}
}
@article {280881,
	title = {Characterization of a spontaneous retinal neovascular mouse model.},
	journal = {PLoS One},
	volume = {9},
	number = {9},
	year = {2014},
	month = {2014},
	pages = {e106507},
	abstract = {BACKGROUND: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. METHODS: The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. RESULTS: We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. CONCLUSIONS: The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0106507},
	author = {Hasegawa, Eiichi and Sweigard, Harry and Husain, Deeba and Olivares, Ana M and Chang, Bo and Smith, Kaylee E and Birsner, Amy E and D{\textquoteright}Amato, Robert J and Michaud, Norman A and Han, Yinan and Vavvas, Demetrios G and Miller, Joan W and Haider, Neena B and Connor, Kip M}
}
@article {1661823,
	title = {An orbital calcific cyst following exenteration},
	journal = {Orbit},
	year = {2022},
	month = {2022 Dec 27},
	pages = {1-4},
	abstract = {A 77-year-old Asian female with a history of left orbit exenteration and lid-sparing reconstruction for recurrent sebaceous carcinoma presented with fluid-like sensation of the left orbit. Magnetic resonance imaging (MRI) demonstrated bright T2 signal and a cyst-like cavity within the exenterated orbit. Decision was made to proceed with surgical exploration and excision. A calcified, bone-like cavity was encountered intraoperatively and removed. Histopathology revealed dense fibrous connective tissue with areas of calcification without osseous metaplasia, suggestive of retained blood in the orbit that underwent dystrophic calcification. This case report illustrates a rare occurrence of a bone-like calcific cyst following exenteration.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2022.2151630},
	author = {Hasegawa, Naomi and Zhao, Jiawei and Greninger, Daniel A and Lu, Jonathan and Yoon, Michael K and Chen, Ying and McCulley, Timothy J}
}
@article {913471,
	title = {Novel Insights Into the Immunoregulatory Function and Localization of Dendritic Cells.},
	journal = {Cornea},
	volume = {35 Suppl 1},
	year = {2016},
	month = {2016 Nov},
	pages = {S49-S54},
	abstract = {Dendritic cells (DCs) are antigen-presenting cells that normally play a critical role in stimulating T-cell-dependent immune responses. However, tolerogenic DCs (CD11cMHC-IICD80CD86) induce immune tolerance by stimulating regulatory T cells (Tregs: CD4CD25Foxp3). Although tolerogenic DCs are used to treat autoimmune diseases and to prevent transplantation rejection, the mechanisms by which they regulate alloimmunity are poorly understood. Here, we review our previous studies aiming to elucidate the mechanisms involved in immune rejection of corneal allografts using a corneal transplant model. We found that donor-derived tolerogenic DCs significantly prolonged corneal allograft survival by suppressing indirect allosensitization. We also reported the precise distribution of intraepithelial corneal DCs, termed Langerhans cells (LCs: CD11cLangerinMHC-II) in the cornea, which we maintain play a critical role in regulating corneal immunity. By confocal microscopy, we constructed 3-dimensional images of corneal LCs, which demonstrated that their cell bodies are present in the basal cell layer of the corneal epithelium. Furthermore, LC dendrites extend toward the ocular surface, but do not connect to epithelial tight junctions, indicating that they cannot directly interact with ocular surface antigens. We confirm the potential of DC therapy for corneal graft rejection and report the function of intraepithelial DCs (LCs) in the normal cornea.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001005},
	author = {Hattori, Takaaki and Takahashi, Hiroki and Dana, Reza}
}
@article {504001,
	title = {Similar Sensitivity to Ladder Contours in Macular Degeneration Patients and Controls.},
	journal = {PLoS One},
	volume = {10},
	number = {7},
	year = {2015},
	month = {2015},
	pages = {e0128119},
	abstract = {PURPOSE: To determine whether people with central field loss (CFL) from macular degeneration have improved ability to recognize a particularly difficult spatial configuration embedded in noise, the peripherally-viewed {\textquoteright}ladder contour{\textquoteright}. The visibility of these configuration has been linked to general contour integration ability and crowding limitations in peripheral vision. METHODS: We used a trial-based yes-no task. CFL patients and normally-sighted controls performed the task, looking for ladder contours embedded in a field of randomly oriented Gabor patches, at a range of stimulus presentation times (varying stimulus difficulty). Viewing eccentricity in CFL patients was set by their preferred retinal loci (PRLs) and matched artificially in the control group. The contours were presented so as to be tangent to the CFL region, given a patient{\textquoteright}s PRL location. RESULTS: CFL and normally-sighted groups performed similarly on the task. The only significant determinant of performance was the viewing eccentricity. CONCLUSIONS: CFL patients do not seem to develop any improved ability to recognize ladder contours with their parafoveal retina, which suggests that there is no underlying improvement in contour integration or reduction in crowding limitations in the region of the PRL despite extended daily use.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0128119},
	author = {Haun, Andrew M and Peli, Eli}
}
@article {1732501,
	title = {Hyperacute Cutibacterium acnes Endophthalmitis Following Cataract Surgery},
	journal = {Retin Cases Brief Rep},
	year = {2023},
	month = {2023 Jul 13},
	abstract = {PURPOSE: Postoperative endophthalmitis is a relatively uncommon, but potentially visually devastating, complication associated with cataract surgery. Specific microbial causes of endophthalmitis are characteristically associated with particular disease time courses. Though Cutibacterium acnes is typically associated with an indolent course of inflammation, we report a case of C. acnes endophthalmitis with onset on postoperative day (POD) 1 and a positive culture from POD 2. METHODS: Case report. RESULTS: A 56-year-old man underwent cataract extraction and posterior chamber intraocular lens placement in his left eye. On POD 1, he presented with severe discomfort, reduced visual acuity, and significant inflammation. On POD 2, his anterior chamber was tapped and injected with broad-spectrum antibiotics and steroids. The inflammation ultimately resolved, and his visual acuity improved to 20/20. CONCLUSIONS: C. acnes is a rare cause of hyperacute onset postoperative endophthalmitis. Maintaining a high clinical suspicion and initiating prompt treatment can help to optimize long-term visual outcomes.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001450},
	author = {Hauser, Blake M and Hoyek, Sandra and Greenstein, Scott H and Patel, Nimesh A}
}
@article {1532328,
	title = {Pars plana vitrectomy combined with penetrating keratoplasty and transscleral-sutured intraocular lens implantation in complex eyes: a case series},
	journal = {BMC Ophthalmol},
	volume = {20},
	number = {1},
	year = {2020},
	month = {2020 Sep 14},
	pages = {369},
	abstract = {BACKGROUND: The aim of this study was to evaluate the clinical outcomes of pars plana vitrectomy (PPV) combined with penetrating keratoplasty (PKP) and transscleral-sutured intraocular lens (IOL) implantation (IOL-suture) in complex eyes. METHODS: In this prospective, consecutive interventional case series, patients who underwent PKP combined with PPV and IOL implantation from July 2014 to March 2018 at Yokohama Minami Kyosai Hospital were enrolled. The postoperative best corrected visual acuity (BCVA) (converted to logarithm of the minimal angle of resolution [logMAR] units), intraocular pressure (IOP, mmHg), endothelial cell density (ECD, cells/mm), graft survival, complications, astigmatism, and spherical equivalent (dioptres [D]) were evaluated. RESULTS: This study included 11 eyes of 11 patients (three females and eight males; mean age, 61.8 {\textpm} 13.9 years) with an injury (n\&nbsp;= 6) or bullous keratopathy (n\&nbsp;= 5). The BCVA significantly improved from 1.50 {\textpm} 0.66 logMAR preoperatively to 0.78 {\textpm} 0.59 logMAR (p\&nbsp;\&lt; 0.001) postoperatively. The baseline ECD significantly decreased from 2396 {\textpm} 238 cells/mm preoperatively to 1132 {\textpm} 323 cells/mm (p\&nbsp;\&lt; 0.001) postoperatively. Despite two rejection episodes, graft survival rates were 100\%. The mean follow-up period was 38.0 {\textpm} 20.5 months. Two patients required combined glaucoma surgery, and three patients underwent subsequent glaucoma surgery. Postoperative astigmatism and spherical equivalent were 3.9 {\textpm} 3.2 D and 0.29 {\textpm} 2.18 D, respectively. CONCLUSION: The combination of PKP, PPV, and IOL-suture implantation could be a safe and effective approach for eyes requiring anterior segment surgery; however, these eyes are associated with a higher incidence of glaucoma surgery.},
	issn = {1471-2415},
	doi = {10.1186/s12886-020-01639-y},
	author = {Hayashi, Takahiko and Yasutsugu, Ida and Shimizu, Toshiki and Kuroki, Tsubasa and Kobashigawa, Yuji and Iijima, Yasuhito and Yuda, Kentaro}
}
@article {1603840,
	title = {The Incidence of Sympathetic Ophthalmia After Trauma: A Meta-analysis},
	journal = {Am J Ophthalmol},
	volume = {234},
	year = {2022},
	month = {2022 Feb},
	pages = {117-125},
	abstract = {PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19\% (95\% CI 0.14\%-0.24\%) and the incidence rate of SO was 33 per 100,000 person-years, (95\% CI 19.61-56.64) with I2 of 13\% and 72\%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.06.036},
	author = {He, Bonnie and Tanya, Stuti M and Wang, Chao and Kezouh, Abbas and Torun, Nurhan and Ing, Edsel}
}
@article {1323926,
	title = {Activation of the EGF Receptor by Histamine Receptor Subtypes Stimulates Mucin Secretion in Conjunctival Goblet Cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {8},
	year = {2018},
	month = {2018 Jul 02},
	pages = {3543-3553},
	abstract = {Purpose: The purpose of this study was to determine if histamine receptors interact with the epidermal growth factor receptor (EGFR) in cultured rat conjunctival goblet cells. Methods: Goblet cells from rat conjunctiva were grown in organ culture. First-passage goblet cells were used in all experiments. Phosphorylated (active) and total EGFR, AKT, and extracellular signal-regulated kinase (ERK)1/2 were measured by Western blot analysis. Cells were preincubated with the EGFR antagonist AG1478 for 30 minutes or small interfering RNA specific to the EGFR for 3 days prior to stimulation with histamine or agonists specific for histamine receptor subtypes for 2 hours. Goblet cell secretion was measured using an enzyme-linked lectin assay. Goblet cells were incubated for 1 hour with the calcium indicator molecule fura-2/AM, and intracellular [Ca2+] ([Ca2+]i) was determined. Data were collected in real time and presented as the actual [Ca2+]i with time and as the change in peak [Ca2+]i. Results: Histamine increased the phosphorylation of the EGFR. Mucin secretion and increase in [Ca2+]i stimulated by histamine, and agonists specific for each histamine receptor subtype were blocked by inhibition of the EGFR. Increase in [Ca2+]i stimulated by histamine and specific agonists for each histamine receptor was also inhibited by TAPI-1, a matrix metalloproteinase (MMP) inhibitor. The histamine-stimulated increase in activation of AKT, but not ERK1/2, was blocked by AG1478. Conclusions: In conjunctival goblet cells, histamine, using all four receptor subtypes, transactivates the EGFR via an MMP. This in turn phosphorylates AKT to increase [Ca2+]i and stimulate mucin secretion.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-2476},
	author = {He, Min and Lippestad, Marit and Li, Dayu and Hodges, Robin R and Utheim, Tor P and Dartt, Darlene A.}
}
@article {959406,
	title = {Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {14},
	year = {2016},
	month = {2016 Nov 01},
	pages = {6134-6146},
	abstract = {Purpose: We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. Methods: We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. Results: Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 {\textpm} 2.2\% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHC-MPC while 84.7 {\textpm} 6.9\% of cells expressed CK7 on PDL-silk. For PCL, 87.10 {\textpm} 3.17\% of cells were CK7-positive compared to PET where 67.10 {\textpm} 12.08\% of cells were CK7-positive cells. Conclusions: Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20081},
	author = {He, Min and Storr-Paulsen, Thomas and Wang, Annie L and Ghezzi, Chiara E and Wang, Siran and Fullana, Matthew and Karamichos, Dimitrios and Utheim, Tor P and Islam, Rakibul and Griffith, May and Islam, M Mirazul and Hodges, Robin R and Wnek, Gary E and Kaplan, David L and Dartt, Darlene A.}
}
@article {313201,
	title = {Endoscopic bimanual approach to an intraconal cavernous hemangioma of the orbital apex with vascularized flap reconstruction.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {30},
	number = {4},
	year = {2014},
	month = {2014 Jul-Aug},
	pages = {e104-6},
	abstract = {The aim of this study was to describe a transnasal endoscopic bimanual technique for the removal of an intraconal orbital apex cavernous hemangioma. Report of a surgical technique. A 39-year-old woman with unilateral visual loss and proptosis was found to have an intraconal orbital apex mass consistent radiographically with cavernous hemangioma. Because of its posteromedial location within the orbit, a transnasal 4-handed endoscopic technique was used with pedicled nasoseptal flap reconstruction. The tumor was excised, and the patient had no complications. The transnasal endoscopic approach to orbital apex cavernous hemangioma excision is a viable surgical approach for these difficult to access lesions. The medial orbital wall may be simultaneously reconstructed to prevent diplopia and enophthalmos.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e3182a22ed1},
	author = {Healy, David Y and Lee, N Grace and Freitag, Suzanne K and Bleier, Benjamin S}
}
@article {560196,
	title = {The effects of simulated vision impairments on the cone of gaze.},
	journal = {Atten Percept Psychophys},
	volume = {77},
	number = {7},
	year = {2015},
	month = {2015 Oct},
	pages = {2399-408},
	abstract = {Detecting the gaze direction of others is critical for many social interactions. We explored factors that may make the perception of mutual gaze more difficult, including the degradation of the stimulus and simulated vision impairment. To what extent do these factors affect the complex assessment of mutual gaze? Using an interactive virtual head whose eye direction could be manipulated by the subject, we conducted two experiments to assess the effects of simulated vision impairments on mutual gaze. Healthy subjects had to demarcate the center and the edges of the cone of gaze-that is, the range of gaze directions that are accepted for mutual gaze. When vision was impaired by adding a semitransparent white contrast reduction mask to the display (Exp. 1), judgments became more variable and more influenced by the head direction (indicative of a compensation strategy). When refractive blur was added (Exp. 1), the gaze cone shrank from 12.9{\textdegree} (no blur) to 11.3{\textdegree} (3-diopter lens), which cannot be explained by a low-level process but might reflect a tightening of the criterion for mutual gaze as a response to the increased uncertainty. However, the overall effects of the impairments were relatively modest. Elderly subjects (Exp. 2) produced more variability but did not differ qualitatively from the younger subjects. In the face of artificial vision impairments, compensation mechanisms and criterion changes allow us to perform better in mutual gaze perception than would be predicted by a simple extrapolation from the losses in basic visual acuity and contrast sensitivity.},
	issn = {1943-393X},
	doi = {10.3758/s13414-015-0931-4},
	author = {Hecht, Heiko and H{\"o}richs, Jenny and Sheldon, Sarah and Quint, Jessilin and Bowers, Alex}
}
@article {1632293,
	title = {Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation},
	journal = {JCI Insight},
	volume = {7},
	number = {6},
	year = {2022},
	month = {2022 Mar 22},
	abstract = {Dyslipidemia and autophagy have been implicated in the pathogenesis of blinding neovascular age-related macular degeneration (NV-AMD). VLDL receptor (VLDLR), expressed in photoreceptors with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acids. Since fatty acid uptake is reduced in Vldlr-/- tissues, more remain in circulation, and the retina is fuel deficient, driving the formation in mice of neovascular lesions reminiscent of retinal angiomatous proliferation (RAP), a subtype of NV-AMD. Nutrient scarcity and energy failure are classically mitigated by increasing autophagy. We found that excess circulating lipids restrained retinal autophagy, which contributed to pathological angiogenesis in the Vldlr-/- RAP model. Triglyceride-derived fatty acid sensed by free fatty acid receptor 1 (FFAR1) restricted autophagy and oxidative metabolism in photoreceptors. FFAR1 suppressed transcription factor EB (TFEB), a master regulator of autophagy and lipid metabolism. Reduced TFEB, in turn, decreased sirtuin-3 expression and mitochondrial respiration. Metabolomic signatures of mouse RAP-like retinas were consistent with a role in promoting angiogenesis. This signature was also found in human NV-AMD vitreous. Restoring photoreceptor autophagy in Vldlr-/- retinas, either pharmacologically or by deleting Ffar1, enhanced metabolic efficiency and suppressed pathological angiogenesis. Dysregulated autophagy by circulating lipids might therefore contribute to the energy failure of photoreceptors driving neovascular eye diseases, and FFAR1 may be a target for intervention.},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.154174},
	author = {Heckel, Emilie and Cagnone, Gael and Agnihotri, Tapan and Cakir, Bertan and Das, Ashim and Kim, Jin Sung and Kim, Nicholas and Lavoie, Genevi{\`e}ve and Situ, Anu and Pundir, Sheetal and Sun, Ye and W{\"u}nnemann, Florian and Pierce, Kerry A and Dennis, Courtney and Mitchell, Grant A and Chemtob, Sylvain and Rezende, Flavio A and Andelfinger, Gregor and Clish, Clary B and Roux, Philippe P and Sapieha, Przemyslaw and Smith, Lois E H and Joyal, Jean-S{\'e}bastien}
}
@article {1773586,
	title = {Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells},
	journal = {J Optom},
	volume = {17},
	number = {1},
	year = {2024},
	month = {2024 Jan-Mar},
	pages = {100481},
	abstract = {PURPOSE: To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC.

METHODS: Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC.

RESULTS: BAK-preserved latanoprost and bimatoprost reduced cell survival by 28\% (p~=~0.0133) and 20\% (p~=~0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54\% (p~=~0.003), BAK-preserved bimatoprost by 45\% (p~=~0.006), PQ-preserved travoprost by 16\% (p~=~0.0041), and PF latanoprost by 19\% (p~=~0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p~=~0.0001 and p~=~0.0019, respectively) compared to a negative control, which PF latanoprost did not.

CONCLUSION: BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.},
	keywords = {Antihypertensive Agents, Benzalkonium Compounds, Bimatoprost, Cloprostenol, Goblet Cells, Humans, Interleukin-8, Latanoprost, Ophthalmic Solutions, Preservatives, Pharmaceutical, Prostaglandins F, Synthetic, Prostaglandins, Synthetic, Travoprost},
	issn = {1989-1342},
	doi = {10.1016/j.optom.2023.100481},
	author = {Hedengran, Anne and Freiberg, Josefine and May Hansen, Pernille and Boix-Lemonche, Gerard and Utheim, Tor P and Dartt, Darlene A. and Petrovski, Goran and Heegaard, Steffen and Kolko, Miriam}
}
@article {1498264,
	title = {Outcomes of strabismus surgery in genetically confirmed congenital fibrosis of the extraocular muscles},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Mar 11},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.03.001},
	author = {Heidary, Gena and Hunter, David G}
}
@article {1354344,
	title = {Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature},
	journal = {J Neuroophthalmol},
	volume = {34},
	number = {1},
	year = {2014},
	month = {2014 Mar},
	pages = {39-43},
	abstract = {Combined oxidative phosphorylation deficiency type 7 (COXPD7) is a rare disorder of mitochondrial metabolism that results in optic atrophy and Leigh syndrome-like disease. We describe 2 siblings with compound heterozygous mutations in the recently identified C12orf65 gene who presented with optic atrophy and mild developmental delays and subsequently developed bilateral, symmetric lesions in the brainstem reminiscent of Leigh syndrome. Repeat neuroimaging demonstrated reversibility of the findings in 1 sibling and persistent metabolic stroke in the other. This article highlights the phenotypic manifestations from a novel mutation in the C12orf65 gene and reviews the clinical presentation of the 5 other individuals reported to date who carry mutations in this gene.},
	keywords = {Child, Child, Preschool, DNA, DNA Mutational Analysis, Female, Follow-Up Studies, Humans, Leigh Disease, Magnetic Resonance Imaging, Male, Mitochondrial Proteins, Mutation, Optic Atrophy, Peptide Termination Factors, Phenotype, Siblings},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000076},
	author = {Heidary, Gena and Calderwood, Laurel and Cox, Gerald F and Robson, Caroline D and Teot, Lisa A and Mullon, Jennifer and Anselm, Irina}
}
@article {1179201,
	title = {Neuro-Ophthalmic Manifestations of Pediatric Neurodegenerative Disease},
	journal = {J Neuroophthalmol},
	volume = {37 Suppl 1},
	year = {2017},
	month = {2017 Sep},
	pages = {S4-S13},
	abstract = {The topic of pediatric neurodegenerative disease is broad and ever expanding. Children who suffer from neurodegenerative disease often have concomitant visual dysfunction. Neuro-ophthalmologists may become involved in clinical care to identify corroborating eye findings when a specific condition is suspected, to monitor for disease progression, and in some cases, to assess treatment efficacy. Ophthalmic findings also may be the harbinger of a neurodegenerative process so a keen awareness of the possible manifestations of these conditions is important. The purpose of this review is to highlight common examples of the neuro-ophthalmic manifestations of pediatric neurodegenerative disease using a case-based approach in an effort to provide a framework for approaching these complex patients.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000549},
	author = {Heidary, Gena}
}
@article {1608595,
	title = {Adjustable Sutures in the Treatment of Strabismus: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {129},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {100-109},
	abstract = {PURPOSE: To review the scientific literature that evaluates the effectiveness of adjustable sutures in the management of strabismus for adult and pediatric patients. METHODS: Literature searches were performed in the PubMed database through April 2021 with no date limitations and were restricted to publications in English. The searches identified 551 relevant citations, of which 55 were reviewed in full text. Of these, 17 articles met the inclusion criteria and were assigned a level of evidence rating by the panel methodologist. The search included all randomized controlled studies regardless of study size and cohort studies of 100 or more patients comparing the adjustable versus nonadjustable suture technique, with a focus on motor alignment outcomes or reoperation rates. RESULTS: The literature search yielded no level I studies. Of the 17 articles that met the inclusion criteria, 11 were rated level II and 6 were rated level III. Among the 12 studies that focused on motor alignment outcomes, 4 small randomized clinical trials (RCTs) did not find a statistically significant difference between groups, although they were powered to detect only very large differences. Seven of 8 nonrandomized studies found a statistically significant difference in motor alignment success in favor of the adjustable suture technique, both overall and in certain subgroups of patients. Successful motor alignment was seen in both exotropia (in 3 studies that were not limited to children) and esotropia (in 1 study of adults and 2 of children). The majority of included studies that reported on reoperation rates found the rates to be lower in patients who underwent strabismus surgery with adjustable sutures, but this finding was not uniformly demonstrated. CONCLUSIONS: Although there are no level I studies evaluating the effectiveness of adjustable sutures for strabismus surgery, the majority of nonrandomized studies that met the inclusion criteria for this assessment reported an advantage of the adjustable suture technique over the nonadjustable technique with respect to motor alignment outcomes. This finding was not uniformly demonstrated among all studies reviewed and warrants further investigation in the development and analysis of adjustable suture techniques.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.07.026},
	author = {Heidary, Gena and Aakalu, Vinay K and Binenbaum, Gil and Chang, Melinda Y and Morrison, David G and VanderVeen, Deborah K and Lambert, Scott R and Trivedi, Rupal H and Galvin, Jennifer A and Pineles, Stacy L}
}
@article {1466899,
	title = {Outcomes of strabismus surgery in genetically confirmed congenital fibrosis of the extraocular muscles},
	journal = {J AAPOS},
	year = {2019},
	month = {2019 Sep 18},
	abstract = {PURPOSE: To detail surgical strategy and strabismus outcomes in a genetically defined cohort of patients with congenital fibrosis of the extraocular muscles (CFEOM). METHODS: A total of 13 patients with genetically confirmed CFEOM (via genetic testing for mutations in KIF21A, PHOX2A, and TUBB3) were retrospectively identified after undergoing strabismus surgery at Boston Children{\textquoteright}s Hospital and surgical outcomes were compared. RESULTS: Age at first surgery ranged from 11 months to 63 years, with an average of 3 strabismus procedures per patient. Ten patients had CFEOM1, of whom 9 had the KIF21A R954W amino acid (AA) substitution and 1 had the M947T AA substitution. Of the 3 with CFEOM3, 2 had the TUBB3 E410K AA substitution, and 1 had a previously unreported E410V AA substitution. CFEOM1 patients all underwent at least 1 procedure to address chin-up posture. Chin-up posture improved from 24{\textdegree} {\textpm} 8{\textdegree} before surgery to 10.0{\textdegree} {\textpm} 8{\textdegree} postoperatively (P \&lt; 0.001). Three CFEOM1 patients developed exotropia after vertical muscle surgery alone; all had the R954W AA substitution. Postoperatively, 1 CFEOM1 patient developed a corneal ulcer. All CFEOM3 patients appeared to have underlying exposure keratopathy, successfully treated with prosthetic replacement of the ocular surface ecosystem (PROSE) lens in 2 patients. CONCLUSIONS: CFEOM is a complex strabismus disorder for which surgical management is difficult. Despite an aggressive surgical approach, multiple procedures may be necessary to achieve a desirable surgical effect. Knowledge of the underlying genetic diagnosis may help to inform surgical management.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.05.018},
	author = {Heidary, Gena and MacKinnon, Sarah and Elliott, Alexandra and Barry, Brenda J and Engle, Elizabeth C and Hunter, David G}
}
@article {1598051,
	title = {Exome-based investigation of the genetic basis of human pigmentary glaucoma},
	journal = {BMC Genomics},
	volume = {22},
	number = {1},
	year = {2021},
	month = {2021 Jun 26},
	pages = {477},
	abstract = {BACKGROUND: Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. RESULTS: Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. CONCLUSIONS: We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.},
	keywords = {Animals, Exome, Glaucoma, Open-Angle, Humans, Iris, Membrane Glycoproteins, Mice, Pigmentation, Whole Exome Sequencing},
	issn = {1471-2164},
	doi = {10.1186/s12864-021-07782-0},
	author = {van der Heide, Carly and Goar, Wes and Meyer, Kacie J and Alward, Wallace L M and Boese, Erin A and Sears, Nathan C and Roos, Ben R and Kwon, Young H and DeLuca, Adam P and Siggs, Owen M and Gonzaga-Jauregui, Claudia and Sheffield, Val C and Kai Wang and Stone, Edwin M and Mullins, Robert F and Anderson, Michael G and Fan, Bao Jian and Ritch, Robert and Craig, Jamie E and Wiggs, Janey L and Scheetz, Todd E and Fingert, John H}
}
@article {1016051,
	title = {ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY},
	journal = {Retina},
	volume = {37},
	number = {11},
	year = {2017},
	month = {2017 Nov},
	pages = {2084-2094},
	abstract = {PURPOSE: To investigate choroidal involvement in acute posterior multifocal placoid pigment epitheliopathy (APMPPE). METHODS: A retrospective observational case series using multimodal imaging including optical coherence tomography (OCT) angiography. RESULTS: Five patients with APMPPE were included. In most acute lesions, OCT angiography revealed outer retinal and retinal pigment epithelium (RPE) hyperreflective lesions with attenuated OCT signal in the underlying choroid, but careful examination allowed us to identify a single lesion with decreased choriocapillaris flow outside the signal attenuation. Optical coherence tomography angiography obtained after healing of lesions revealed areas of hypointense circular flow voids clustered in groups surrounded by either isointense or hyperintense signal background. Point-by-point evaluation revealed these flow voids did not correspond to areas of RPE thickening or focal pigmentary changes. Larger hypointense lesions were observed and did correlate with pigmentary changes. CONCLUSION: Our case series demonstrates choriocapillaris flow abnormalities in acute APMPPE extending beyond the OCT lesions, and distinct residual vascular abnormalities in healed APMPPE lesions on OCT angiography. Our findings support a primary ischemic insult to the photoreceptors and RPE, but choriocapillaris flow abnormalities could be secondary to (OCT invisible) retinal and RPE involvement. The lack of understanding of the etiology along with the inability to visualize most of the choroid in acute lesions precludes definite conclusions about the true pathogenesis of APMPPE.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001487},
	author = {Heiferman, Michael J and Rahmani, Safa and Jampol, Lee M and Nesper, Peter L and Skondra, Dimitra and Kim, Leo A and Fawzi, Amani A}
}
@article {1761786,
	title = {Validation of the Iowa Head-Mounted Open-Source Perimeter},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {9},
	year = {2023},
	month = {2023 Sep 01},
	pages = {19},
	abstract = {PURPOSE: To assess the validity of visual field (VF) results from the Iowa Head-Mounted Display (HMD) Open-Source Perimeter and to test the hypothesis that VF defects and test-retest repeatability are similar between the HMD and Octopus 900 perimeters. METHODS: We tested 20 healthy and nine glaucoma patients on the HMD and Octopus 900\&nbsp;perimeters using the Open Perimetry Interface platform with size V stimuli, a custom grid spanning the central 26{\textdegree} of the VF, and a ZEST thresholding algorithm. Historical data from the Humphrey Field Analyzer (HFA) were also analyzed. Repeatability was analyzed with the repeatability coefficient (RC), and VF defect detection was determined through side-by-side comparisons. RESULTS: The pointwise RCs were 2.6 dB and 3.4 dB for the HMD and Octopus 900\&nbsp;perimeters in ocular healthy subjects, respectively. Likewise, the RCs were 4.2 dB and 3.5 dB, respectively, in glaucomatous patients. Limits of agreement between the HMD and Octopus 900 perimeters were {\textpm}4.6 dB (mean difference, 0.4 dB) for healthy patients and {\textpm}8.9 dB (mean difference, 0.1 dB) for glaucomatous patients. Retrospective analysis showed that pointwise RCs on the HFA2 perimeter were between 3.4 and 3.7 dB for healthy patients and between 3.9 and 4.7 dB for glaucoma patients. VF defects were similar between the HMD and Octopus 900 for glaucoma subjects. CONCLUSIONS: The Iowa Virtual Reality HMD Open-Source Perimeter is as repeatable as the Octopus 900 perimeter and is a more portable and less expensive alternative than traditional perimeters. TRANSLATIONAL RELEVANCE: This study demonstrates the validity of the visual field results from the Iowa HMD Open-Source Perimeter which may help expand perimetry access.},
	keywords = {Eye, Glaucoma, Humans, Iowa, Retrospective Studies, Visual Field Tests},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.9.19},
	author = {Heinzman, Zachary and Linton, Edward and Mar{\'\i}n-Franch, Iv{\'a}n and Turpin, Andrew and Alawa, Karam and Wijayagunaratne, Anushi and Wall, Michael}
}
@article {1580491,
	title = {Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP},
	journal = {Neonatology},
	year = {2021},
	month = {2021 Feb 19},
	pages = {1-10},
	abstract = {INTRODUCTION: Thrombocytopenia has been identified as an independent risk factor for retinopathy of prematurity (ROP), although underlying mechanisms are unknown. In this study, the association of platelet count and serum platelet-derived factors with ROP was investigated. METHODS: Data for 78 infants born at gestational age (GA) \&lt;28 weeks were included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. RESULTS: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p \&lt; 0.05-0.001). With adjustment for GA, low platelet counts and low serum concentrations of all 3 factors at PMA 32 weeks were significantly associated with severe ROP. Serum concentrations of all 3 factors also strongly correlated with platelet count (p \&lt; 0.001). CONCLUSION: In this article, we show that ROP, platelet counts, and specific pro-angiogenic factors correlate. These data suggest that platelet-released factors might be involved in the regulation of retinal and systemic angiogenesis after extremely preterm birth. Further investigations are needed.},
	issn = {1661-7819},
	doi = {10.1159/000512282},
	author = {Hellgren, Gunnel and Lundgren, Pia and Pivodic, Aldina and L{\"o}fqvist, Chatarina and Nilsson, Anders K and Ley, David and S{\"a}vman, Karin and Smith, Lois E and Hellstr{\"o}m, Ann}
}
@article {541221,
	title = {Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.},
	journal = {Pediatr Res},
	year = {2015},
	month = {2015 Sep 15},
	abstract = {BACKGROUND: The role of VEGF in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP. METHODS: This study included 52 infants born at \&lt;31 weeks gestational age (non-ROP n=33, non-proliferative ROP n=10, treated for ROP n=9). VEGF concentrations were analyzed in blood samples collected at birth, at 3 days postnatal age, and then weekly until at least a gestational age of 35 weeks. RESULTS: VEGF concentrations at birth did not differ between groups, independent of later ROP status. In contrast, VEGF serum concentrations were significantly higher at first detection of ROP in infants who were later treated for ROP compared to infants without ROP. At the time of laser therapy, serum VEGF concentrations did not differ between groups. CONCLUSION: Circulatory concentrations of VEGF, in infants who later developed severe ROP, were elevated at the time when ROP first was detected but not at the time when current treatment most often occurred. This supports the need for further studies of circulating VEGF in relation to the timing of ROP treatment.Pediatric Research (2015); doi:10.1038/pr.2015.181.},
	issn = {1530-0447},
	doi = {10.1038/pr.2015.181},
	author = {Hellgren, Gunnel and L{\"o}fqvist, Chatarina and H{\r a}rd, Anna-Lena and Hansen-Pupp, Ingrid and Gram, Magnus and Ley, David and Smith, Lois E and Hellstr{\"o}m, Ann}
}
@article {1307466,
	title = {Increased postnatal concentrations of pro-inflammatory cytokines are associated with reduced IGF-I levels and retinopathy of prematurity},
	journal = {Growth Horm IGF Res},
	volume = {39},
	year = {2018},
	month = {2018 Apr},
	pages = {19-24},
	abstract = {OBJECTIVE: Retinopathy of prematurity (ROP) is a multifactorial disease linked to low insulin-like growth factor (IGF)-I levels and perhaps to postnatal inflammation. Here, we investigated the longitudinal postnatal serum concentrations of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in relation to IGF-I levels and ROP. DESIGN: The study cohort included 52 infants born before 31 gestational weeks. The infants were screened for ROP and classified as non-ROP (n=33), non-proliferative ROP (stages 1 and 2; n=10), or proliferative ROP (stage 3, all treated for ROP; n=9). Blood samples were collected at birth, 24h after birth, and then weekly until at least 36weeks postmenstrual age (PMA) (i.e., up to 13weeks after birth). Circulating levels of IL-6 and TNF-α were evaluated in relation to circulating IGF-I levels and ROP. RESULTS: IL-6 levels negatively correlated with IGF-I levels between 5 and 8weeks after birth, (p\&lt;0.01 to p\&lt;0.05). At birth, the IL-6 and TNF-α levels were similar independent of later ROP. Twenty-four hours after birth, both IL-6 and TNF-α levels had increased in infants later treated for ROP (p\&lt;0.05). Postnatal, infants treated for ROP had higher IL-6 levels than infants without ROP. CONCLUSIONS: The pro-inflammatory response is associated with low IGF-I levels and the development of ROP.},
	issn = {1532-2238},
	doi = {10.1016/j.ghir.2017.11.006},
	author = {Hellgren, Gunnel and L{\"o}fqvist, Chatarina and Hansen-Pupp, Ingrid and Gram, Magnus and Smith, Lois E and Ley, David and Hellstr{\"o}m, Ann}
}
@article {647356,
	title = {Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.},
	journal = {Acta Paediatr},
	volume = {105},
	number = {6},
	year = {2016},
	month = {2016 Jun},
	pages = {576-86},
	abstract = {UNLABELLED: Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities. CONCLUSION: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants.},
	issn = {1651-2227},
	doi = {10.1111/apa.13350},
	author = {Hellstr{\"o}m, Ann and Ley, David and Hansen-Pupp, Ingrid and Hallberg, Boubou and L{\"o}fqvist, Chatarina and van Marter, Linda and van Weissenbruch, Mirjam and Ramenghi, Luca A and Beardsall, Kathryn and Dunger, David and H{\r a}rd, Anna-Lena and Smith, Lois E H}
}
@article {1424803,
	title = {Tailored vs Static Oxygen Saturation Targets to Prevent Retinopathy of Prematurity},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Feb 14},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.6940},
	author = {Hellstr{\"o}m, Ann and H{\r a}rd, Anna-Lena and Smith, Lois E H}
}
@article {1213821,
	title = {IGF-1 as a drug for preterm infants: a step-wise clinical development},
	journal = {Curr Pharm Des},
	year = {2017},
	month = {2017 Oct 02},
	abstract = {BACKGROUND: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants. METHODS: In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 μg/kg), that increased serum IGF-1 to levels close to those observed in fetuses and preterm infants of similar GAs. Thereafter, a Phase I 3 hours IV infusion of rhIGF-1/rhIGFBP-3 was conducted in 5 infants, followed by a Phase II study with four sections (A-D). In the Phase II, sections A-D studies, time on infusion increased and younger gestational ages were included. RESULTS: IV infusion increased IGF-1 but with short half-life (0.5h) implying a need for continuous infusion. In order to obtain in utero levels of IGF-I, the dose was increased from 100 to 250 μg/kg/24 h and the infusion was prolonged from 3 weeks postnatal age until a postmenstrual age of 29 weeks and 6 days. CONCLUSION: The purpose has been to ensure high-quality research into the development of a new drug for preterm infants. We hope that our work will help to establish a new standard for the testing of medications for preterm infants.},
	issn = {1873-4286},
	doi = {10.2174/1381612823666171002114545},
	author = {Hellstrom, Ann and Ley, David and Hallberg, Boubou and Lofqvist, Chatarina and Hansen-Pupp, Ingrid and Ramenghi, Luca A and Borg, Jan and Smith, Lois E H and Hard, Anna-Lena}
}
@article {1651363,
	title = {Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort},
	journal = {BMJ Open},
	year = {2022},
	author = {Hellstr{\"o}m, A and Jacobson, L and Al-Hawasi, A and Hellstr{\"o}m-Westas, L and Rakow, A and Johnson, M and S{\"a}vman, K and Holmstrom, G and Larsson, E and Gr{\"a}nse, L and Saric, M and Sunnqvist, B and Smith, L and H{\r a}rd, AL and Morsing, E and Lundgren, P}
}
@article {913476,
	title = {Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants.},
	journal = {Am J Perinatol},
	volume = {33},
	number = {11},
	year = {2016},
	month = {2016 Sep},
	pages = {1067-71},
	abstract = {The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.},
	issn = {1098-8785},
	doi = {10.1055/s-0036-1586109},
	author = {Hellstr{\"o}m, Ann and Ley, David and Hansen-Pupp, Ingrid and Hallberg, Boubou and Ramenghi, Luca A and L{\"o}fqvist, Chatarina and Smith, Lois E H and H{\r a}rd, Anna-Lena}
}
@article {1619425,
	title = {Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants},
	journal = {JAMA Netw Open},
	volume = {4},
	number = {10},
	year = {2021},
	month = {2021 Oct 01},
	pages = {e2128771},
	abstract = {Importance: Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. Objective: To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. Design, Setting, and Participants: This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. Main Outcomes and Measures: Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95\% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. Results: A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6\%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95\% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95\% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95\% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. Conclusions and Relevance: This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.},
	issn = {2574-3805},
	doi = {10.1001/jamanetworkopen.2021.28771},
	author = {Hellstr{\"o}m, Ann and Pivodic, Aldina and Gr{\"a}nse, Lotta and Lundgren, Pia and Sj{\"o}bom, Ulrika and Nilsson, Anders K and S{\"o}derling, Helena and H{\r a}rd, Anna-Lena and Smith, Lois E H and L{\"o}fqvist, Chatarina Alice}
}
@article {1580480,
	title = {Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial},
	journal = {JAMA Pediatr},
	volume = {175},
	number = {4},
	year = {2021},
	month = {2021 Apr 01},
	pages = {359-367},
	abstract = {Importance: Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). Objective: To determine whether enteral supplementation with fatty acids from birth to 40 weeks{\textquoteright} postmenstrual age reduces ROP in extremely preterm infants. Design, Setting, and Participants: The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks{\textquoteright} gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. Interventions: Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks{\textquoteright} postmenstrual age. Main Outcomes and Measures: The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. Results: A total of 101 infants (58 boys [57.4\%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2\%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8\%] in the AA:DHA group vs 35 of 105 [33.3\%] in the control group; adjusted relative risk, 0.50 [95\% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol\% [95\% CI, 0.46-1.18 mol\%]; P \&lt; .001; overall mean difference in control group, 0.13 mol\% [95\% CI, 0.01-0.24 mol\%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5\%] vs 48 of 105 [45.7\%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6\%] vs 42 of 105 [40.0\%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6\%) and 53 of 105 infants (50.5\%), serious adverse events occurred in 26 of 101 infants (25.7\%) and 26 of 105 infants (24.8\%), and 16 of 101 infants (15.8\%) and 13 of 106 infants (12.3\%) died. Conclusions and Relevance: This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50\% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT03201588.},
	issn = {2168-6211},
	doi = {10.1001/jamapediatrics.2020.5653},
	author = {Hellstr{\"o}m, Ann and Nilsson, Anders K and Wackernagel, Dirk and Pivodic, Aldina and Vanpee, Mireille and Sj{\"o}bom, Ulrika and Hellgren, Gunnel and Hallberg, Boubou and Domell{\"o}f, Magnus and Klevebro, Susanna and Hellstr{\"o}m, William and Andersson, Mats and Lund, Anna-My and L{\"o}fqvist, Chatarina and Elfvin, Anders and S{\"a}vman, Karin and Hansen-Pupp, Ingrid and H{\r a}rd, Anna-Lena and Smith, Lois E H and Ley, David}
}
@article {1522730,
	title = {Docosahexaenoic Acid and Arachidonic Acid Levels Are Associated with Early Systemic Inflammation in Extremely Preterm Infants},
	journal = {Nutrients},
	volume = {12},
	number = {7},
	year = {2020},
	month = {2020 Jul 05},
	abstract = {Fetal and early postnatal inflammation have been associated with increased morbidity in extremely preterm infants. This study aimed to demonstrate if postpartum levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) were associated with early inflammation. In a cohort of 90 extremely preterm infants, DHA and AA in cord blood, on the first postnatal day and on postnatal day 7 were examined in relation to early systemic inflammation, defined as elevated C-reactive protein (CRP) and/or interleukin-6 (IL-6) within 72 h from birth, with or without positive blood culture. Median serum level of DHA was 0.5 mol\% (95\% CI (confidence interval) 0.2-0.9, = 0.006) lower than the first postnatal day in infants with early systemic inflammation, compared to infants without signs of inflammation, whereas levels of AA were not statistically different between infants with and without signs of inflammation. In cord blood, lower serum levels of both DHA (correlation coefficient -0.40; = 0.010) and AA (correlation coefficient -0.54; \&lt; 0.001) correlated with higher levels of IL-6. Levels of DHA or AA did not differ between infants with and without histological signs of chorioamnionitis or fetal inflammation. In conclusion, serum levels of DHA at birth were associated with the inflammatory response during the early postnatal period in extremely preterm infants.},
	issn = {2072-6643},
	doi = {10.3390/nu12071996},
	author = {Hellstr{\"o}m, Ann and Hellstr{\"o}m, William and Hellgren, Gunnel and Smith, Lois E H and Puttonen, Henri and Fyhr, Ing-Marie and S{\"a}vman, Karin and Nilsson, Anders K and Klevebro, Susanna}
}
@article {1364611,
	title = {Integrated genome analysis suggests that most conserved non-coding sequences are regulatory factor binding sites},
	journal = {Nucleic Acids Res},
	volume = {40},
	number = {16},
	year = {2012},
	month = {2012 Sep},
	pages = {7858-69},
	abstract = {More than 98\% of a typical vertebrate genome does not code for proteins. Although non-coding regions are sprinkled with short (\&lt;200 bp) islands of evolutionarily conserved sequences, the function of most of these unannotated conserved islands remains unknown. One possibility is that unannotated conserved islands could encode non-coding RNAs (ncRNAs); alternatively, unannotated conserved islands could serve as promoter-distal regulatory factor binding sites (RFBSs) like enhancers. Here we assess these possibilities by comparing unannotated conserved islands in the human and mouse genomes to transcribed regions and to RFBSs, relying on a detailed case study of one human and one mouse cell type. We define transcribed regions by applying a novel transcript-calling algorithm to RNA-Seq data obtained from total cellular RNA, and we define RFBSs using ChIP-Seq and DNAse-hypersensitivity assays. We find that unannotated conserved islands are four times more likely to coincide with RFBSs than with unannotated ncRNAs. Thousands of conserved RFBSs can be categorized as insulators based on the presence of CTCF or as enhancers based on the presence of p300/CBP and H3K4me1. While many unannotated conserved RFBSs are transcriptionally active to some extent, the transcripts produced tend to be unspliced, non-polyadenylated and expressed at levels 10 to 100-fold lower than annotated coding or ncRNAs. Extending these findings across multiple cell types and tissues, we propose that most conserved non-coding genomic DNA in vertebrate genomes corresponds to promoter-distal regulatory elements.},
	keywords = {Animals, Base Sequence, Binding Sites, Conserved Sequence, DNA, Genome, HeLa Cells, Humans, Mice, Promoter Regions, Genetic, Regulatory Elements, Transcriptional, RNA, Untranslated, Transcription, Genetic},
	issn = {1362-4962},
	doi = {10.1093/nar/gks477},
	author = {Hemberg, Martin and Gray, Jesse M and Cloonan, Nicole and Kuersten, Scott and Grimmond, Sean and Greenberg, Michael E and Kreiman, Gabriel}
}
@article {1364612,
	title = {Intraoperative wavefront aberrometry in cataract surgery},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {100-6},
	abstract = {Intraoperative wavefront aberrometry is a relatively new technology that aims to improve refractive outcomes following cataract surgery by optimizing the spherical power of the intraocular lens implant or calculating the appropriate axis and power of toric lenses during cataract surgery in an aphakic state. This article reviews the literature on intraoperative wavefront aberrometry and provides a critical assessment of the benefits and shortcomings of that technology.},
	keywords = {Aberrometry, Cataract Extraction, Corneal Wavefront Aberration, Humans, Intraoperative Period},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.708809},
	author = {Hemmati, Houman D and Gologorsky, Daniel and Pineda, Roberto}
}
@article {1653573,
	title = {Gliovascular alterations in sporadic and familial Alzheimer{\textquoteright}s disease: APOE3 Christchurch homozygote glioprotection},
	journal = {Brain Pathol},
	volume = {33},
	number = {2},
	year = {2023},
	month = {2023 Mar},
	pages = {e13119},
	abstract = {In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer{\textquoteright}s disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aβ. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.},
	keywords = {Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E3, Brain, Homozygote, Humans, Mutation},
	issn = {1750-3639},
	doi = {10.1111/bpa.13119},
	author = {Henao-Restrepo, Juli{\'a}n and L{\'o}pez-Murillo, Carolina and Valderrama-Carmona, Pablo and Orozco-Santa, Natalia and Gomez, Johana and Guti{\'e}rrez-Vargas, Johanna and Moraga, Renato and Toledo, Jorge and Littau, Jessica Lisa and H{\"a}rtel, Steffen and Arboleda-Vel{\'a}squez, Joseph F and Sepulveda-Falla, Diego and Lopera, Francisco and Cardona-G{\'o}mez, Gloria Patricia and Villegas, Andr{\'e}s and Posada-Duque, Rafael}
}
@article {1661610,
	title = {Use of Telemedicine in Pediatric Ophthalmology in the Underserved Population},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {116-123},
	abstract = {Access to pediatric eye care is critical in diagnosing and treating eye disease promptly to prevent visual impairment. The demand for pediatric ophthalmology is high, even in developed countries, and significant socioeconomic disparities exist in access to care. The purpose of this article is to summarize the current literature on the use of telemedicine in pediatric ophthalmology in the underserved population and to identify areas of opportunity. A detailed literature review was performed in PubMed and Google Scholar on October 1, 2021. All articles in English that described the use of telemedicine in pediatric ophthalmology, with particular attention to the underserved pediatric population, were included. There is a paucity of literature on the visual outcomes from pediatric teleophthalmology alone, and even less in underserved populations specifically. Literature supports its use in subacute to chronic eye disease, return and postoperative visits, and screening for retinopathy in prematurity in particular. Collaboration between pediatric optometrists and pediatric ophthalmologists for both asynchronous and synchronous care delivery models has shown promise in several studies. It is essential to operate within the limits of pediatric teleophthalmology and utilize this valuable service for its strengths. Telemedicine may expand access to pediatric ophthalmologists in underserved populations and may reduce the burden of eye disease.},
	keywords = {Child, Delivery of Health Care, Eye Diseases, Humans, Ophthalmology, Telemedicine, Vulnerable Populations},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152703},
	author = {Hennein, Lauren and Jastrzembski, Benjamin and Shah, Ankoor S}
}
@article {1626093,
	title = {Thyroid-Associated Orbitopathy: Management and Treatment},
	journal = {J Binocul Vis Ocul Motil},
	year = {2021},
	month = {2021 Dec 07},
	pages = {1-15},
	abstract = {Thyroid-associated orbitopathy (TAO) is a leading cause of orbital and strabismus symptoms in adults. Over the last decade, new treatments have greatly changed available options to alleviate symptoms and improve outcomes. This article discusses the pathophysiology and natural disease course of TAO, including when to pursue urgent treatment and when to consider other diagnoses. This article highlights the interventions that may alter the disease course and offers a comprehensive review on evidence-based interventions for both supportive therapy and systemic agents. The surgical strategies and principles for the treatment of TAO are discussed, including indications for combined surgical interventions and varying surgical techniques.},
	issn = {2576-1218},
	author = {Hennein, Lauren and Robbins, Shira L}
}
@article {314136,
	title = {Characterization of circulating and endothelial progenitor cells in patients with extreme-duration type 1 diabetes.},
	journal = {Diabetes Care},
	volume = {37},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {2193-201},
	abstract = {OBJECTIVE: We characterized and correlated endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) with lack of vascular complications in the Joslin Medalist Study in patients with type 1 diabetes for 50 years or longer. RESEARCH DESIGN AND METHODS: EPC and CPC levels were ascertained by flow cytometry and compared among Medalists (n = 172) with or without diabetic retinopathy (DR; n = 84 of 162), neuropathy (n = 94 of 165), diabetic nephropathy (DN; n = 18 of 172), cardiovascular disease (CVD; n = 63 of 168), age-matched controls (n = 83), type 2 diabetic patients (n = 36), and younger type 1 diabetic patients (n = 31). Mitogens, inflammatory cytokines, and oxidative markers were measured in blood or urine. Migration of cultured peripheral blood mononuclear cells (PBMCs) from Medalists and age-matched controls were compared. RESULTS: Medalists{\textquoteright} EPC and CPC levels equaled those of their nondiabetic age-matched controls, were 10\% higher than those in younger type 1 diabetic patients, and were 20\% higher than those in age-matched type 2 diabetic patients. CPC levels were 15\% higher in Medalists without CVD and nephropathy than in those affected, whereas EPC levels were significantly higher in those without peripheral vascular disease (PVD) than those with PVD. Stromal-derived factor 1 (SDF-1) levels were higher in Medalists with CVD, DN, and DR than in those not affected and their controls. IGF-I levels were lower in Medalists and correlated inversely with CPC levels. Additionally, cultured PBMCs from Medalists migrated more than those from nondiabetic controls. CONCLUSIONS: Normal levels of EPC and CPC in the Medalists, unlike other groups with diabetes, especially those without CVD, support the idea that endogenous factors exist to neutralize the adverse effects of metabolic abnormalities of diabetes on vascular tissues.},
	issn = {1935-5548},
	doi = {10.2337/dc13-2547},
	author = {Hernandez, Sonia L and Gong, Jennifer H and Chen, Liming and Wu, I-Hsien and Sun, Jennifer K and Keenan, Hillary A and King, George L}
}
@article {1522740,
	title = {Symptoms of ocular surface disease in construction workers: comparative study with office workers},
	journal = {BMC Ophthalmol},
	volume = {20},
	number = {1},
	year = {2020},
	month = {2020 Jul 09},
	pages = {272},
	abstract = {BACKGROUND: To investigate and contrast the prevalence of dry eye symptoms in construction workers and office workers using the OSDI questionnaire. METHODS: A cross-sectional, observational study was conducted using the OSDI questionnaire to evaluate dry eye symptoms and associated risk factors. Sampled size calculation with a power of 80\% and a 95\% degree of confidence suggested the inclusion of 298 participants. RESULTS: We studied 304 subjects (149 construction workers and 155 office workers). More than half (55\%) of the participants presented dry eye symptoms (OSDI \&gt; 12). The average OSDI score was 21.30 {\textpm} 22.20 points, being lower in the group of construction workers (12.45 {\textpm} 17.50) than in-office workers (28.51 {\textpm} 22.99) (p \&lt; \&nbsp;0.001). Considering participants who had moderate and severe symptoms (23 to 100 points in OSDI), office workers presented dry eye symptoms 4.15 times more frequently than construction workers (OR 4.15, 95\% CI 2.52, 6.85). Women presented statistical evidence of higher OSDI scores than men (32.47 {\textpm} 23.72 vs. 14.87 {\textpm} 18.48, respectively). CONCLUSIONS: construction workers have four times less risk of presenting dry eye symptoms than people working in the average office space. This highlights the pernicious effects on the ocular surface of the office environment, which poses a significant risk for the development or worsening of dry eye symptoms.},
	issn = {1471-2415},
	doi = {10.1186/s12886-020-01548-0},
	author = {Hernandez-Llamas, Sergio and Paz-Ramos, Ana Karen and Marcos-Gonzalez, Patricio and Amparo, Francisco and Garza-Leon, Manuel}
}
@article {1603867,
	title = {Altered Blood Flow in the Ophthalmic and Internal Carotid Arteries in Patients with Age-Related Macular Degeneration Measured Using Noncontrast MR Angiography at 7T},
	journal = {AJNR Am J Neuroradiol},
	year = {2021},
	month = {2021 Jul 01},
	abstract = {BACKGROUND AND PURPOSE: Age-related macular degeneration is associated with reduced perfusion of the eye; however, the role of altered blood flow in the upstream ophthalmic or internal carotid arteries is unclear. We used ultra-high-field MR imaging to investigate whether the diameter of and blood flow in the ophthalmic artery and/or the ICA are altered in age-related macular degeneration and whether any blood flow changes are associated with disease progression. MATERIALS AND METHODS: Twenty-four patients with age-related macular degeneration and 13 similarly-aged healthy controls participated. TOF and high-resolution dynamic 2D phase-contrast MRA (0.26 {\texttimes} 0.26 {\texttimes} 2mm3, 100-ms effective sampling rate) was acquired at 7T. Vessel diameters were calculated from cross-sectional areas in phase-contrast acquisitions. Blood flow time-series were measured across the cardiac cycle. RESULTS: The ophthalmic artery vessel diameter was found to be significantly smaller in patients with age-related macular degeneration than in controls. Volumetric flow through the ophthalmic artery was significantly lower in patients with late age-related macular degeneration, with a significant trend of decreasing volumetric ophthalmic artery flow rates with increasing disease severity. The resistance index was significantly greater in patients with age-related macular degeneration than in controls in the ophthalmic artery. Flow velocity through the ophthalmic artery and ICA was significantly higher in patients with age-related macular degeneration. Ophthalmic artery blood flow as a percentage of ipsilateral ICA blood flow was nearly double in controls than in patients with age-related macular degeneration. CONCLUSIONS: These findings support the hypothesis that vascular changes upstream to the eye are associated with the severity of age-related macular degeneration. Additional investigation into the potential causality of this relationship and whether treatments that improve ocular circulation slow disease progression is warranted.},
	issn = {1936-959X},
	doi = {10.3174/ajnr.A7187},
	author = {Hibert, M L and Chen, Yi and Ohringer, N and Feuer, W J and Waheed, N K and Heier, J S and Calhoun, M W and Rosenfeld, P J and Polimeni, JR}
}
@article {1549018,
	title = {Systemic Disease and Ocular Comorbidity Analysis of Geographically Isolated Federally Recognized American Indian Tribes of the Intermountain West},
	journal = {J Clin Med},
	volume = {9},
	number = {11},
	year = {2020},
	month = {2020 Nov 07},
	abstract = {BACKGROUND: The American Indian Navajo and Goshute peoples are underserved patient populations residing in the Four Corners area of the United States and Ibupah, Utah, respectively. METHODS: We conducted a cross-sectional study of epidemiological factors and lipid biomarkers that may be associated with type II diabetes, hypertension and retinal manifestations in tribal and non-tribal members in the study areas (n = 146 participants). We performed multivariate analyses to determine which, if any, risk factors were unique at the tribal level. Fundus photos and epidemiological data through standardized questionnaires were collected. Blood samples were collected to analyze lipid biomarkers. Univariate analyses were conducted and statistically significant factors at \&lt; 0.10 were entered into a multivariate regression. RESULTS: Of 51 participants for whom phenotyping was available, from the Four Corners region, 31 had type II diabetes (DM), 26 had hypertension and 6 had diabetic retinopathy (DR). Of the 64 participants from Ibupah with phenotyping available, 20 had diabetes, 19 had hypertension and 6 had DR. Navajo participants were less likely to have any type of retinopathy as compared to Goshute participants (odds ratio (OR) = 0.059; 95\% confidence interval (CI) = 0.016-0.223; \&lt; 0.001). Associations were found between diabetes and hypertension in both populations. Older age was associated with hypertension in the Four Corners, and the Navajo that reside there on the reservation, but not within the Goshute and Ibupah populations. Combining both the Ibupah, Utah and Four Corners study populations, being American Indian ( = 0.022), residing in the Four Corners ( = 0.027) and having hypertension ( \&lt; 0.001) increased the risk of DM. DM ( \&lt; 0.001) and age ( = 0.002) were significantly associated with hypertension in both populations examined. When retinopathy was evaluated for both populations combined, hypertension ( = 0.037) and living in Ibupah ( \&lt; 0.001) were associated with greater risk of retinopathy. When combining both American Indian populations from the Four Corners and Ibupah, those with hypertension were more likely to have DM ( \&lt; 0.001). No lipid biomarkers were found to be significantly associated with any disease state. CONCLUSIONS: We found different comorbid factors with retinal disease outcome between the two tribes that reside within the Intermountain West. This is indicated by the association of tribe and with the type of retinopathy outcome when we combined the populations of American Indians. Overall, the Navajo peoples and the Four Corners had a higher prevalence of chronic disease that included diabetes and hypertension than the Goshutes and Ibupah. To the best of our knowledge, this is the first study to conduct an analysis for disease outcomes exclusively including the Navajo and Goshute tribe of the Intermountain West.},
	issn = {2077-0383},
	doi = {10.3390/jcm9113590},
	author = {Hicks, Patrice M and Haaland, Benjamin and Feehan, Michael and Crandall, Alan S and Pettey, Jeff H and Nuttall, Elizabeth and Self, William and Hartnett, Mary Elizabeth and Bernstein, Paul and Vitale, Albert and Shakoor, Akbar and Shulman, Julia P and Sieminski, Sandra F and Kim, Ivana and Owen, Leah A and Murtaugh, Maureen A and Noyes, Albert and Deangelis, Margaret M}
}
@article {1328884,
	title = {Understanding the evolving phenotype of vascular complications in telomere biology disorders},
	journal = {Angiogenesis},
	volume = {22},
	number = {1},
	year = {2019},
	month = {2019 Feb},
	pages = {95-102},
	abstract = {Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.},
	issn = {1573-7209},
	doi = {10.1007/s10456-018-9640-7},
	author = {Higgs, Cecilia and Crow, Yanick J and Adams, Denise M and Chang, Emmanuel and Hayes, Don and Herbig, Utz and Huang, James N and Himes, Ryan and Jajoo, Kunal and Johnson, F Brad and Reynolds, Susan D and Yonekawa, Yoshihiro and Armanios, Mary and Boulad, Farid and DiNardo, Courtney D and Dufour, Carlo and Goldman, Frederick D and Khan, Shakila and Kratz, Christian and Myers, Kasiani C and Raghu, Ganesh and Alter, Blanche P and Aubert, Geraldine and Bhala, Sonia and Cowen, Edward W and Dror, Yigal and El-Youssef, Mounif and Friedman, Bruce and Giri, Neelam and Helms Guba, Lisa and Khincha, Payal P and Lin, Tiffany F and Longhurst, Hilary and McReynolds, Lisa J and Nelson, Adam and Olson, Tim and Pariser, Anne and Perona, Rosario and Sasa, Ghadir and Schratz, Kristen and Simonetto, Douglas A and Townsley, Danielle and Michael Walsh and Stevens, Katherine and Agarwal, Suneet and Bertuch, Alison A and Savage, Sharon A and Clinical Care Consortium for Telomere-associated Ailments (CCCTAA)}
}
@article {1598056,
	title = {NF-κB activation in retinal microglia is involved in the inflammatory and neovascularization signaling in laser-induced choroidal neovascularization in mice},
	journal = {Exp Cell Res},
	volume = {403},
	number = {1},
	year = {2021},
	month = {2021 Jun 01},
	pages = {112581},
	abstract = {PURPOSE: To evaluate Nuclear Factor NF-κB (NF-κB) signaling on microglia activation, migration, and angiogenesis in laser-induced choroidal neovascularization (CNV). METHODS: Nine-week-old C57BL/6 male mice were randomly assigned to IMD-0354 treated or untreated groups (5 mice, 10 eyes per group). CNV was induced with a 532-nm laser. Laser spots (power 250\&nbsp;mW, spot size 100\&nbsp;μm, time of exposure 50\&nbsp;ms) were created in each eye using a slit-lamp delivery system. Selective inhibitor of nuclear factor kappa-B kinase subunit beta (IKK2) inhibitor IMD-0354 (10\&nbsp;μg) was delivered subconjunctivally; vehicle-treated mice were the control. The treatment effect on CNV development was assessed at five days post-CNV induction in vivo in C57BL/6 and Cx3cr1gfp/wt mice by fluorescent angiography, fundus imaging, and ex vivo by retinal flatmounts immunostaining and Western blot analysis of RPE/Choroidal/Scleral complexes (RCSC) lysates. In vitro evaluations of IMD-0354 effects were performed in the BV-2 microglial cell line using lipopolysaccharide (LPS) stimulation. RESULTS: IMD-0354 caused a significant reduction in the fluorescein leakage and size of the laser spot, as well as a reduction in microglial cell migration and suppression of phospho-IκBα, Vascular endothelial growth factor (VEGF-A), and Prostaglandin-endoperoxide synthase 2 (COX-2). In vivo and ex vivo observations demonstrated reduced lesion size in mice, CD68, and Allograft inflammatory factor 1 (IBA-1) positive microglia cells migration to the laser injury site in IMD-0354 treated eyes. The data further corroborate with GFP-positive cells infiltration of the CNV site in Cx3cr1wt/gfp mice. In vitro IMD-0354 (10-25\&nbsp;ng/ml) treatment reduced NF-κB activation, expression of COX-2, caused decreased Actin-F presence and organization, resulting in reduced BV-2\&nbsp;cells migration capacity. CONCLUSION: The present data indicate that NF-κB activation in microglia and it{\textquoteright}s migration capacity is involved in the development of laser CNV in mice. Its suppression by NF-κB inhibition might be a promising therapeutic strategy for wet AMD.},
	issn = {1090-2422},
	doi = {10.1016/j.yexcr.2021.112581},
	author = {Hikage, Fumihito and Lennikov, Anton and Mukwaya, Anthony and Lachota, Mieszko and Ida, Yosuke and Utheim, Tor Paaske and Chen, Dong Feng and Huang, Hu and Ohguro, Hiroshi}
}
@article {1549036,
	title = {Homozygous deletion of 21q22.2 in a patient with hypotonia, developmental delay, cortical visual impairment, and retinopathy},
	journal = {Am J Med Genet A},
	volume = {185},
	number = {2},
	year = {2021},
	month = {2021 02},
	pages = {555-560},
	abstract = {21q22 contains several dosage sensitive genes that are important in neurocognitive development. Determining impacts of gene dosage alterations in this region can be useful in establishing contributions of these genes to human development and disease. We describe a 15-month-old girl with a 1,140 kb homozygous deletion in the Down Syndrome Critical Region at 21q22.2 including 4 genes; B3GALT5, IGSF5, PCP4, DSCAM, and a microRNA (MIR4760). Clinical singleton genome sequencing did not report any candidate gene variants for the patient{\textquoteright}s phenotype. She presented with hypotonia, global developmental delay, cortical visual impairment, and mild facial dysmorphism. Ophthalmological exam was suggestive of retinopathy. We propose that the absence of DSCAM and PCP4 may contribute to the patient{\textquoteright}s neurological and retinal phenotype, while the role of absent B3GALT5 and IGSF5 in her presentation remain unclear at this time.},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.61969},
	author = {Hildebrandt, Clara and Fulton, Anne and Rodan, Lance H}
}
@article {1364613,
	title = {The regulatory roles of apoptosis-inducing factor in the formation and regression processes of ocular neovascularization},
	journal = {Am J Pathol},
	volume = {181},
	number = {1},
	year = {2012},
	month = {2012 Jul},
	pages = {53-61},
	abstract = {The role of apoptosis in the formation and regression of neovascularization is largely hypothesized, although the detailed mechanism remains unclear. Inflammatory cells and endothelial cells both participate and interact during neovascularization. During the early stage, these cells may migrate into an angiogenic site and form a pro-angiogenic microenvironment. Some angiogenic vessels appear to regress, whereas some vessels mature and remain. The control mechanisms of these processes, however, remain unknown. Previously, we reported that the prevention of mitochondrial apoptosis contributed to cellular survival via the prevention of the release of proapoptotic factors, such as apoptosis-inducing factor (AIF) and cytochrome c. In this study, we investigated the regulatory role of cellular apoptosis in angiogenesis using two models of ocular neovascularization: laser injury choroidal neovascularization and VEGF-induced corneal neovascularization in AIF-deficient mice. Averting apoptosis in AIF-deficient mice decreased apoptosis of leukocytes and endothelial cells compared to wild-type mice and resulted in the persistence of these cells at angiogenic sites in vitro and in vivo. Consequently, AIF deficiency expanded neovascularization and diminished vessel regression in these two models. We also observed that peritoneal macrophages from AIF-deficient mice showed anti-apoptotic survival compared to wild-type mice under conditions of starvation. Our data suggest that AIF-related apoptosis plays an important role in neovascularization and that mitochondria-regulated apoptosis could offer a new target for the treatment of pathological angiogenesis.},
	keywords = {Animals, Apoptosis, Apoptosis Inducing Factor, Bone Marrow Transplantation, Choroid, Choroidal Neovascularization, Corneal Neovascularization, Endothelial Cells, Endothelium, Vascular, Fluorescein Angiography, Lasers, Leukocytes, Macrophages, Peritoneal, Male, Mice, Mice, Mutant Strains, Vascular Endothelial Growth Factor A},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2012.03.022},
	author = {Hisatomi, Toshio and Nakao, Shintaro and Murakami, Yusuke and Noda, Kousuke and Nakazawa, Toru and Notomi, Shoji and Connolly, Edward and She, Haicheng and Almulki, Lama and Ito, Yasuhiro and Vavvas, Demetrios G and Ishibashi, Tatsuro and Miller, Joan W}
}
@article {504021,
	title = {Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind.},
	journal = {Ophthalmology},
	volume = {122},
	number = {8},
	year = {2015},
	month = {2015 Aug},
	pages = {1547-54},
	abstract = {PURPOSE: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN: The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS: There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS: The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS: A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS: The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.04.032},
	author = {Ho, Allen C and Humayun, Mark S and Dorn, Jessy D and da Cruz, Lyndon and Dagnelie, Gislin and Handa, James and Barale, Pierre-Olivier and Sahel, Jos{\'e}-Alain and Stanga, Paulo E and Hafezi, Farhad and Safran, Avinoam B and Salzmann, Joel and Santos, Arturo and Birch, David and Spencer, Rand and Cideciyan, Artur V and de Juan, Eugene and Duncan, Jacque L and Eliott, Dean and Fawzi, Amani and Olmos de Koo, Lisa C and Brown, Gary C and Haller, Julia A and Regillo, Carl D and Del Priore, Lucian V and Arditi, Aries and Geruschat, Duane R and Greenberg, Robert J and Argus II Study Group}
}
@article {1653610,
	title = {Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {2},
	year = {2023},
	month = {2023 Mar-Apr 01},
	pages = {150-155},
	abstract = {PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77\% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P \&lt; 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS ( P \&lt; 0.01) and reduction in ocular motility restriction ( P \&lt; 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.},
	keywords = {COVID-19, Cross-Sectional Studies, Exophthalmos, Female, Graves Ophthalmopathy, Humans, Male, Middle Aged},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002267},
	author = {Ho, Tiffany C and Maamari, Robi N and Kossler, Andrea L and Sears, Connie M and Freitag, Suzanne K and Reshef, Edith R and Shinder, Roman and Rootman, Daniel B and Diniz, Stefania B and Kahana, Alon and Schlachter, Dianne and Do, Thai H and Kally, Peter and Turner, Sara and Mokhtarzadeh, Ali and Harrison, Andrew R and Hwang, Christopher J and Kim, Hee Joon and Avila, Sarah A and Thomas, Dilip A and Magazin, Maja and Wester, Sara T and Lee, Wendy W and Clauss, Kevin D and Holds, John B and Sniegowski, Matthew and Compton, Christopher J and Briggs, Christian and Malik, Amina I and Lucarelli, Mark J and Burkat, Cat N and Patel, Luv G and Couch, Steven M}
}
@article {1363119,
	title = {Tear film mucins: front line defenders of the ocular surface; comparison with airway and gastrointestinal tract mucins},
	journal = {Exp Eye Res},
	volume = {117},
	year = {2013},
	month = {2013 Dec},
	pages = {62-78},
	abstract = {The ocular surface including the cornea and conjunctiva and its overlying tear film are the first tissues of the eye to interact with the external environment. The tear film is complex containing multiple layers secreted by different glands and tissues. Each layer contains specific molecules and proteins that not only maintain the health of the cells on the ocular surface by providing nourishment and removal of waste products but also protect these cells from environment. A major protective mechanism that the corneal and conjunctival cells have developed is secretion of the innermost layer of the tear film, the mucous layer. Both the cornea and conjunctiva express membrane spanning mucins, whereas the conjunctiva also produces soluble mucins. The mucins present in the tear film serve to maintain the hydration of the ocular surface and to provide lubrication and anti-adhesive properties between the cells of the ocular surface and conjunctiva during the blink. A third function is to contribute to the epithelial barrier to prevent pathogens from binding to the ocular surface. This review will focus on the different types of mucins produced by the corneal and conjunctival epithelia. Also included in this review will be a presentation of the structure of mucins, regulation of mucin production, role of mucins in ocular surface diseases, and the differences in mucin production by the ocular surface, airways and gastrointestinal tract.},
	keywords = {Conjunctiva, Cornea, Epithelium, Gastrointestinal Tract, Humans, Mucins, Respiratory Mucosa, Tears},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2013.07.027},
	author = {Hodges, Robin R and Dartt, Darlene A.}
}
@article {688611,
	title = {Lipoxin A4 activates ALX/FPR2 receptor to regulate conjunctival goblet cell secretion.},
	journal = {Mucosal Immunol},
	volume = {10},
	number = {1},
	year = {2017},
	pages = {46-57},
	abstract = {Conjunctival goblet cells play a major role in maintaining the mucus layer of the tear film under physiological conditions as well as in inflammatory diseases like dry eye and allergic conjunctivitis. Resolution of inflammation is mediated by proresolution agonists such as lipoxin A4 (LXA4) that can also function under physiological conditions. The purpose of this study was to determine the actions of LXA4 on cultured rat conjunctival goblet cell mucin secretion, intracellular [Ca(2+)] ([Ca(2+)]i), and identify signaling pathways activated by LXA4. ALX/FPR2 (formyl peptide receptor2) was localized to goblet cells in rat conjunctiva and in cultured goblet cells. LXA4 significantly increased mucin secretion, [Ca(2+)]i, and extracellular regulated kinase 1/2 (ERK 1/2) activation. These functions were inhibited by ALX/FPR2 inhibitors. Stable analogs of LXA4 increased [Ca(2+)]i to the same extent as LXA4. Sequential addition of either LXA4 or resolvin D1 followed by the second compound decreased [Ca(2+)]i of the second compound compared with its initial response. LXA4 activated phospholipases C, D, and A2 and downstream molecules protein kinase C, ERK 1/2, and Ca(2+)/calmodulin-dependent kinase to increase mucin secretion and [Ca(2+)]i. We conclude that conjunctival goblet cells respond to LXA4 to maintain the homeostasis of the ocular surface and could be a novel treatment for dry eye diseases.},
	issn = {1935-3456},
	doi = {10.1038/mi.2016.33},
	author = {Hodges, R R and Li, D and Shatos, M A and Bair, J A and Lippestad, M and Serhan, C N and Dartt, D A}
}
@article {959411,
	title = {Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016 Nov 08},
	pages = {36124},
	abstract = {Conjunctival goblet cells synthesize and secrete mucins which play an important role in protecting the ocular surface. Pro-resolution mediators, such as lipoxin A4 (LXA4), are produced during inflammation returning the tissue to homeostasis and are also produced in non-inflamed tissues. The purpose of this study was to determine the actions of LXA4 on cultured human conjunctival goblet cell mucin secretion and increase in intracellular [Ca(2+)] ([Ca(2+)]i) and on histamine-stimulated responses. LXA4 increased mucin secretion and [Ca(2+)]i, and activated ERK1/2 in human goblet cells. Addition of LXA4 before resolvin D1 (RvD1) decreased RvD1 responses though RvD1 did not block LXA4 responses. LXA4 inhibited histamine-stimulated increases in mucin secretion, [Ca(2+)]i, and ERK1/2 activation through activation of β-adrenergic receptor kinase 1. We conclude that conjunctival goblet cells respond to LXA4 through the ALX/FPR2 receptor to maintain homeostasis of the ocular surface and regulate histamine responses and could provide a new therapeutic approach for allergic conjunctivitis and dry eye diseases.},
	issn = {2045-2322},
	doi = {10.1038/srep36124},
	author = {Hodges, Robin R and Li, Dayu and Shatos, Marie A and Serhan, Charles N and Dartt, Darlene A.}
}
@article {836856,
	title = {Signaling Pathways of Purinergic Receptors and Their Interactions with Cholinergic and Adrenergic Pathways in the Lacrimal Gland.},
	journal = {J Ocul Pharmacol Ther},
	volume = {32},
	number = {8},
	year = {2016},
	month = {2016 Oct},
	pages = {490-497},
	abstract = {PURPOSE: Purinergic receptors play a key role in the function of the lacrimal gland (LG) as P1 purinergic receptors A1, A2A, and A2B, P2X1-7 receptors, and many of the P2Y receptors are expressed. METHODS: This review examines the current knowledge of purinergic receptors in the LG as well as the signaling pathways activated by these receptors. RESULTS: These receptors are expressed on the acinar, ductal, and myoepithelial cells. Considerable crosstalk exists between the pathways activated by P2X7 receptors with those activated by M3 muscarinic or α1D adrenergic receptors. The mechanism of the crosstalk between P2X7 and M3 muscarinic receptors differs from that of the crosstalk between P2X7 and α1D adrenergic receptors. CONCLUSIONS: Understanding purinergic receptors and how they modulate protein secretion could play a key role in normal and pathological responses of the LG.},
	issn = {1557-7732},
	doi = {10.1089/jop.2016.0008},
	author = {Hodges, Robin R and Dartt, Darlene A.}
}
@article {1364614,
	title = {Signaling pathways used by EGF to stimulate conjunctival goblet cell secretion},
	journal = {Exp Eye Res},
	volume = {103},
	year = {2012},
	month = {2012 Oct},
	pages = {99-113},
	abstract = {The purpose of this study was to identify the signaling pathways that epidermal growth factor (EGF) uses to stimulate mucin secretion from cultured rat conjunctival goblet cells and to compare the pathways used by EGF with those used by the known secretagogue muscarinic, cholinergic agonists. To this end, goblet cells from rat conjunctiva were grown in culture using RPMI media. For immunofluorescence experiments, antibodies against EGF receptor (EGFR) and ERK 2 as well as muscarinic receptors (M(1)AchR, M(2)AchR, and M(3)AchR) were used, and the cells viewed by fluorescence microscopy. Intracellular [Ca(2+)] ([Ca(2+)](i)) was measured using fura 2/AM. Glycoconjugate secretion was determined after cultured goblet cells were preincubated with inhibitors, and then stimulated with EGF or the cholinergic agonist carbachol (Cch). Goblet cell secretion was measured using an enzyme-linked lectin assay with UEA-I or ELISA for MUC5AC. In cultured goblet cells EGF stimulated an increase in [Ca(2+)](i) in a concentration-dependent manner. EGF-stimulated increase in [Ca(2+)](i) was blocked by inhibitors of the EGF receptor and removal of extracellular Ca(2+). Inhibitors against the EGFR and ERK 1/2 blocked EGF-stimulated mucin secretion. In addition, cultured goblet cells expressed M(1)AchR, M(2)AchR, and M(3)AchRs. Cch-stimulated increase in [Ca(2+)](i) was blocked by inhibitors for the M(1)AchRs, matrix metalloproteinases, and EGF receptors. Inhibitors against the EGF receptor and ERK 1/2 also blocked Cch-stimulated mucin secretion. We conclude that in conjunctival goblet cells, EGF itself increases [Ca(2+)](i) and activates ERK 1/2 to stimulate mucin secretion. EGF-stimulated secretion is dependent on extracellular Ca(2+). This mechanism of action is similar to cholinergic agonists that use muscarinic receptors to transactivate the EGF receptor, increase [Ca(2+)](i), and activate ERK 1/2 leading to an increase in mucin secretion.},
	keywords = {Animals, Blotting, Western, Calcium, Cells, Cultured, Cholinergic Agonists, Conjunctiva, Dose-Response Relationship, Drug, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Epidermal Growth Factor, ErbB Receptors, Fura-2, Goblet Cells, Male, Microscopy, Fluorescence, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mucin 5AC, Rats, Rats, Sprague-Dawley, RNA, Small Interfering, Signal Transduction},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2012.08.010},
	author = {Hodges, Robin R and Bair, Jeffrey A and Carozza, Richard B and Li, Dayu and Shatos, Marie A and Dartt, Darlene A.}
}
@article {691761,
	title = {A retrospective survey of childhood glaucoma prevalence according to Childhood Glaucoma Research Network classification.},
	journal = {Indian J Ophthalmol},
	volume = {64},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {118-23},
	abstract = {PURPOSE: To evaluate the Childhood Glaucoma Research Network (CGRN) classification system and describe the prevalence of each subtype according to this classification. MATERIALS AND METHODS: Retrospectively, the medical records of 205 consecutive childhood glaucoma and glaucoma suspect patients at an urban tertiary care center were reviewed. The initial diagnosis and new diagnosis according to CGRN classification were recorded. RESULTS: All patients fit one of the seven categories of the new classification. Seventy-one percent of diagnoses were changed upon reclassification. Twenty-three percent of patients had primary glaucoma (juvenile open-angle glaucoma and primary congenital glaucoma [PCG]); 36\% had secondary glaucoma (glaucoma associated with nonacquired ocular anomalies; glaucoma associated with nonacquired systemic disease or syndrome; glaucoma associated with acquired condition; and glaucoma following cataract surgery); and 39\% were glaucoma suspect. Of the patients diagnosed with glaucoma, PCG was the most common diagnosis, seen in 32\% of patients. CONCLUSION: The CGRN classification provides a useful method of classifying childhood glaucoma.},
	issn = {1998-3689},
	doi = {10.4103/0301-4738.179716},
	author = {Hoguet, Ambika and Grajewski, Alana and Hodapp, Elizabeth and Chang, Ta Chen Peter}
}
@article {341686,
	title = {Unexpected Hypotony After Glaucoma Drainage Implant Surgery Associated With Anti-Vascular Endothelial Growth Factor Treatment.},
	journal = {JAMA Ophthalmol},
	year = {2014},
	month = {2014 Dec 4},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.5058},
	author = {Hoguet, Ambika and Parrish, Richard K}
}
@article {1359931,
	title = {The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {126},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {611-622},
	abstract = {PURPOSE: To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma. METHODS: Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded because of poor study design and lack of relevance to the topic under evaluation. RESULTS: The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4\% and 15\% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. CONCLUSIONS: Intravitreal injection of anti-VEGF agents results in an immediate and transient increase in IOP. A long-term increase in IOP also may be seen, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Although pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.11.019},
	author = {Hoguet, Ambika and Chen, Philip P and Junk, Anna K and Mruthyunjaya, Prithvi and Nouri-Mahdavi, Kouros and Radhakrishnan, Sunita and Takusagawa, Hana L and Chen, Teresa C}
}
@article {1782431,
	title = {Disentangling the neurological basis of chronic ocular pain using clinical, self-report, and brain imaging data: use of K-means clustering to explore patient phenotypes},
	journal = {Front Neurol},
	volume = {14},
	year = {2023},
	month = {2023},
	pages = {1265082},
	abstract = {INTRODUCTION: The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms. METHODS: We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations. RESULTS: Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms. DISCUSSION: Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.},
	issn = {1664-2295},
	doi = {10.3389/fneur.2023.1265082},
	author = {Holmes, Scott and Reyes, Nicholas and Huang, Jaxon J and Galor, Anat and Pattany, Pradip M and Felix, Elizabeth R and Moulton, Eric A}
}
@article {1016056,
	title = {Periocular breast carcinoma metastases: correlation of clinical, radiologic and histopathologic features},
	journal = {Clin Exp Ophthalmol},
	year = {2017},
	month = {2017 Feb 09},
	abstract = {IMPORTANCE: To describe presenting patterns of breast cancer metastases to the orbit and eyelids BACKGROUND: To provide clinical, radiographic, and pathologic correlations of breast metastases to the orbit or eyelids and evaluate radiographic volumetric orbital changes DESIGN: Retrospective review in an academic center PARTICIPANTS: Ten female patients with periocular metastatic breast carcinoma who were seen at the Massachusetts Eye and Ear Infirmary Oculoplastics Clinic METHODS: Retrospective review of patient records, imaging and pathology findings. MAIN OUTCOME MEASURES: Presenting clinical characteristics, radiographic findings, and histopathological features were assessed and correlated to discover distinctive presenting patterns. Volumetric measurements of the tumors and orbital soft tissue structures were made on magnetic resonance imaging studies. RESULTS: The breast metastases included 9 orbital and 1 eyelid lesions. Two distinct clinical presentations were observed. The first consisted of seven patients who had either enophthalmos or euphthalmos in the setting of a retrobulbar lesion, a radiographically indistinct lesion, and a classic microscopic invasive lobular breast carcinoma (ILBC) with a prominent fibrotic stroma. The second group consisted of two proptotic patients with mass lesions on imaging and an atypical ILBC pathological subtype (pleomorphic or alveolar). One patient had diffusely indurated eyelid fullness. Volumetric analyses demonstrated variable tumor sizes with an inconsistent impact on the orbital volume and fat. CONCLUSIONS AND RELEVANCE: This correlative study provides the clinical-radiographic-histopathologic basis for separating two overarching phenotypic presentations of metastatic breast carcinoma to the orbit. Previously postulated mechanisms for the distinctive finding of tumor-induced enophthalmos are re-examined in the light of the foregoing conclusions.},
	issn = {1442-9071},
	doi = {10.1111/ceo.12926},
	author = {Homer, Natalie and Jakobiec, Frederick A and Stagner, Anna and Cunnane, Mary Elizabeth and Freitag, Suzanne K and Fay, Aaron and Yoon, Michael K}
}
@article {961711,
	title = {Evaluation of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Fellowship Program Website Content and Quality},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {6},
	year = {2017},
	month = {2017 Nov/Dec},
	pages = {471-473},
	abstract = {PURPOSE: The qualities that applicants value in the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) fellowship programs have been studied, but the availability of this information on program websites has not yet been reviewed. The authors evaluated the availability of resident-valued ASOPRS fellowship program information on the Internet. METHODS: The authors performed an Internet search of the 53 ASOPRS fellowship program websites and evaluated websites for 20 characteristics of interest to ASOPRS fellowship applicants such as teaching faculty, program description, rotation schedule, operative cases, and interview information. RESULTS: Of the 53 ASOPRS fellowship programs, 43 (81.1\%) had a fellowship program-dedicated website. The fellowship websites contained a mean 7.6 characteristics (38.1\%, range 0-15). Faculty listing, program description, and case diversity were the most commonly included data (74.4\%, 72.1\%, and 69.8\%, respectively). Fellow selection process, interview information, and graduate job placement were least commonly included (7.0\%, 2.3\%, and 0.0\%, respectively). There was no significant difference in website inclusiveness based on fellowship region or faculty number. Programs affiliated with an ophthalmology residency were more complete than those that were not (40.3\% vs. 20.0\%, p = 0.0098). CONCLUSIONS: This review found that most programs had websites and contained a reasonable number of characteristics. However, applicant-valued information regarding surgical volume, procedure variety, application information, and postgraduate employment history were often missing. American Society of Ophthalmic Plastic and Reconstructive Surgery fellowship programs may improve match outcomes by providing and enhancing program websites with details that their applicants seek.},
	keywords = {Education, Medical, Graduate, Humans, Internship and Residency, Ophthalmologic Surgical Procedures, Ophthalmology, Program Evaluation, Reconstructive Surgical Procedures, Societies, Medical, United States, Web Browser},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000830},
	author = {Homer, Natalie and Yoon, Michael K}
}
@article {1417560,
	title = {Assessment of Infraorbital Hypesthesia Following Orbital Floor and Zygomaticomaxillary Complex Fractures Using a Novel Sensory Grading System},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {1},
	year = {2019},
	month = {2019 Jan/Feb},
	pages = {53-55},
	abstract = {PURPOSE: Introduction of a novel sensory grading system to assess the incidence and long-term recovery of infraorbital hypesthesia following orbital floor and inferior orbital rim fractures. METHODS: Patients who presented for evaluation of orbital floor and/or zygomaticomaxillary complex (ZMC) fractures between January 2015 and April 2016 were analyzed. Two-point subjective infraorbital sensory grading in 5 discrete anatomic areas was performed. Fractures were repaired based on traditional criteria; hypesthesia was not an indication for surgery. The sensory grading system was repeated a mean 21.7 months (range 18-28) after initial fracture. RESULTS: Sixty-two patients (mean 41.8 years) participated in the initial symptom grading, and 42 patients (67.7\%) completed the 2-year follow-up. Overall, 20 of 42 patients (47.6\%) had some infraorbital hypesthesia. There were fewer with isolated orbital floor fractures versus ZMC fractures (31.8\% vs. 68.4\%; p = 0.019). Two years postinjury, 9.1\% and 40.0\% with isolated floor and ZMC fractures, respectively, had persistent sensory disturbance (p = 0.0188). Of patients with sensory disturbance on presentation, 71.4\% with isolated floor fractures and 38.5\% with ZMC fractures experienced complete sensory recovery (p = 0.1596). Patients with isolated floor fractures had improved recovery after surgery (100\% vs. 33.3\% recovery; p = 0.0410). Patients with ZMC fractures showed no difference in sensory prognosis between those repaired and observed. CONCLUSIONS: In this pilot study, isolated orbital floor fractures carried a good infraorbital sensory prognosis, further improved by surgical repair. Zygomaticomaxillary complex fractures portended a worse long-term sensory outcome, unaffected by management strategy. This study validates the novel sensory grading system in post-fracture analysis.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001162},
	author = {Homer, Natalie and Glass, Lora R and Lee, N Grace and Lefebvre, Daniel R and Sutula, Francis C and Freitag, Suzanne K and Yoon, Michael K}
}
@article {1328885,
	title = {Management of Long-Standing Flaccid Facial Palsy: Periocular Considerations},
	journal = {Otolaryngol Clin North Am},
	volume = {51},
	number = {6},
	year = {2018},
	month = {2018 Dec},
	pages = {1107-1118},
	abstract = {Ineffective eyelid closure can pose a serious risk of injury to the ocular surface and eye. In cases of eyelid paresis, systematic examination of the eye and ocular adnexa will direct appropriate interventions. Specifically, 4 distinct periorbital regions should be independently assessed: eyebrow, upper eyelid, ocular surface, and lower eyelid. Corneal exposure can lead to dehydration, thinning, scarring, infection, perforation, and blindness. Long-term sequelae following facial nerve palsy may also include epiphora, gustatory lacrimation, and synkinesis.},
	issn = {1557-8259},
	doi = {10.1016/j.otc.2018.07.007},
	author = {Homer, Natalie and Fay, Aaron}
}
@article {504031,
	title = {Limitations of Keratoplasty in China: A Survey Analysis.},
	journal = {PLoS One},
	volume = {10},
	number = {7},
	year = {2015},
	month = {2015},
	pages = {e0132268},
	abstract = {PURPOSE: Each year, over 8,000 corneal transplantation surgeries are performed in China. Unlike developed countries, which have established standard requirements for operative experience for corneal specialists, little information exists on surgical training for keratoplasty in China. The aim of this study was to assess the keratoplasty experience of Chinese corneal specialists and to characterize their surgical patterns. METHODS: One hundred and twenty-one corneal specialists in 16 provinces (65 cities) in China were invited to complete an anonymous survey at the 2014 Chinese Corneal Society annual meeting, which consisted of questions with single or multiple-choice answers. Demographics, the number and type of keratoplasties performed, and the perceived limiting factors for performing keratoplasties were analyzed. RESULTS: An overwhelming 89\% response rate was achieved. Of the 108 respondents, 76\% worked in tertiary centers, and only 23\% held a medical doctorate degree. Furthermore, 69\% of the participants had received corneal fellowship training of less than one year. Only 71\% were capable of keratoplasties. Among those doing keratoplasty, 68\% performed less than 50 keratoplasties each year. Of the same group of keratoplasty surgeons, 88\% of corneal specialists capable of keratoplasties had performed penetrating keratoplasties, 87\% had performed lamellar keratoplasties, 12\% had performed deep anterior lamellar keratoplasties, and 5\% had performed Descemet{\textquoteright}s stripping endothelial keratoplasties. When questioned on the reasons for the low number of keratoplasties performed in China, the respondents deemed the following factors most important: lack of surgical training (71\%), a shortage of donor supply (52\%), and a lack of curricula (42\%). A multivariate logistic regression analysis showed that corneal transplantation capabilities are significantly associated with responders{\textquoteright} education levels and training time. CONCLUSION: Keratoplasty surgery experience is suboptimal for Chinese corneal specialists. Penetrating and lamellar keratoplasties are the preferred surgical patterns. Our findings raise concerns about the adequacy of keratoplasty training in China.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0132268},
	author = {Hong, Jiaxu and Shi, Weiyun and Liu, Zuguo and Pineda, Roberto and Cui, Xinhan and Sun, Xinghuai and Xu, Jianjiang}
}
@article {1789131,
	title = {Thermal-plex: fluidic-free, rapid sequential multiplexed imaging with DNA-encoded thermal channels},
	journal = {Nat Methods},
	volume = {21},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {331-341},
	abstract = {Multiplexed fluorescence imaging is typically limited to three- to five-plex on standard setups. Sequential imaging methods based on iterative labeling and imaging enable practical higher multiplexing, but generally require a complex fluidic setup with several rounds of slow buffer exchange (tens of minutes to an hour for each exchange step). We report the thermal-plex method, which removes complex and slow buffer exchange steps and provides fluidic-free, rapid sequential imaging. Thermal-plex uses simple DNA probes that are engineered to fluoresce sequentially when, and only when, activated with transient exposure to heating spikes at designated temperatures (thermal channels). Channel switching is fast (\&lt;30 s) and is achieved with a commercially available and affordable on-scope heating device. We demonstrate 15-plex RNA imaging (five thermal {\texttimes} three fluorescence channels) in fixed cells and retina tissues in less than 4 min, without using buffer exchange or fluidics. Thermal-plex introduces a new labeling method for efficient sequential multiplexed imaging.},
	keywords = {DNA, Optical Imaging, RNA, Temperature},
	issn = {1548-7105},
	doi = {10.1038/s41592-023-02115-3},
	author = {Hong, Fan and Kishi, Jocelyn Y and Delgado, Ryan N and Jeong, Jiyoun and Saka, Sinem K and Su, Hanquan and Cepko, Constance L and Peng Yin}
}
@article {1573103,
	title = {Nationwide incidence and treatment pattern of retinopathy of prematurity in South Korea using the 2007-2018 national health insurance claims data},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Jan 14},
	pages = {1451},
	abstract = {The aim of this study is to investigate the nationwide incidence and treatment pattern of retinopathy of prematurity (ROP) in South Korea. Using the population-based National Health Insurance database (2007-2018), the nationwide incidence of ROP among premature infants with a gestational age (GA) \&lt; 37\&nbsp;weeks (GA \&lt; 28\&nbsp;weeks, GA28; 28\&nbsp;weeks <= GA \&lt; 37\&nbsp;weeks; GA28-37) and the percentage of ROP infants who underwent treatment [surgery (vitrectomy, encircling/buckling); retinal ablation (laser photocoagulation, cryotherapy)] were evaluated. We identified 141,964 premature infants, 42,300 of whom had ROP, with a nationwide incidence of 29.8\%. The incidence of ROP in GA28 group was 4.3 times higher than in GA28-37 group (63.6\% [2240/3522] vs 28.9\% [40,060/138,442], p \&lt; 0.001). As for the 12-year trends, the incidence of ROP decreased from 39.5\% (3308/8366) in 2007 to 23.5\% (2943/12,539) in 2018. 3.0\% of ROP infants underwent treatment (25.0\% in GA28; 1.7\% in GA28-37); 0.2\% (84/42,300) and 2.9\% (1214/42,300) underwent surgery and retinal ablation, respectively. The overall percentage of ROP infants who underwent treatment has decreased from 4.7\% in 2007 to 1.8\% in 2018. This first Korean nationwide epidemiological study of ROP revealed a decreased incidence of ROP and a decreased percentage of ROP infants undergoing conventional treatment during a 12-year period.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-80989-z},
	author = {Hong, Eun Hee and Shin, Yong Un and Bae, Gi Hwan and Choi, Youngjin and Ahn, Seong Joon and Sobrin, Lucia and Hong, Rimkyung and Kim, Inah and Cho, Heeyoon}
}
@article {1363120,
	title = {Bacterial keratitis in Shanghai},
	journal = {Ophthalmology},
	volume = {120},
	number = {3},
	year = {2013},
	month = {2013 Mar},
	pages = {647},
	keywords = {Corneal Ulcer, Eye Infections, Bacterial, Female, Gram-Negative Bacterial Infections, Gram-Positive Bacterial Infections, Humans, Male},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2012.10.038},
	author = {Hong, Jiaxu and Xu, Jianjiang and Hua, Jing and Sun, Xinghuai}
}
@article {688616,
	title = {Ambient air pollution, weather changes, and outpatient visits for allergic conjunctivitis: A retrospective registry study.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016},
	pages = {23858},
	abstract = {Allergic conjunctivitis is a common problem that significantly impairs patients{\textquoteright} quality of life. Whether air pollution serves as a risk factor for the development of allergic conjunctivitis remains elusive. In this paper, we assess the relationship between air pollutants and weather conditions with outpatient visits for allergic conjunctivitis. By using a time-series analysis based on the largest dataset ever assembled to date, we found that the number of outpatient visits for allergic conjunctivitis was significantly correlated with the levels of NO2, O3, and temperature, while its association with humidity was statistically marginal. No associations between PM10, PM2.5, SO2, or wind velocity and outpatient visits were seen. Subgroup analyses showed that sex seemed to modify the effects of humidity on outpatient visits for allergic conjunctivitis, but not for NO2, O3, or temperature. People younger than 40 were found to be susceptible to changes of all four parameters, while those older than 40 were only consistently affected by NO2 levels. Our findings revealed that higher levels of ambient NO2, O3, and temperature increase the chances of outpatient visits for allergic conjunctivitis. Ambient air pollution and weather changes may contribute to the worsening of allergic conjunctivitis.},
	issn = {2045-2322},
	doi = {10.1038/srep23858},
	author = {Hong, Jiaxu and Zhong, Taoling and Li, Huili and Xu, Jianming and Ye, Xiaofang and Mu, Zhe and Lu, Yi and Mashaghi, Alireza and Zhou, Ying and Tan, Mengxi and Li, Qiyuan and Sun, Xinghuai and Liu, Zuguo and Xu, Jianjiang}
}
@article {1580511,
	title = {Quantitatively comparing weekly changes in retinal vascular characteristics of eyes eventually treated versus not treated for retinopathy of prematurity},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Feb 20},
	abstract = {PURPOSE: To quantitatively compare retinal vascular characteristics over time in eyes eventually treated versus not treated for retinopathy of prematurity (ROP), using ROPtool analysis of narrow-field retinal images. METHODS: This longitudinal study used prospectively collected narrow-field retinal images of infants screened for ROP, prior to treatment, if needed. Images were analyzed using a methodology that combines quadrant-level measures from several images of the same eye. For the longitudinal analysis, one examination per postmenstrual age (PMA) was included per eye. We compared the following ROPtool indices and their change per week between eyes eventually treated versus not treated for ROP: tortuosity index (TI), dilation index (DI), sum of adjusted indices (SAI), and tortuosity-weighted plus (TWP). Analysis was performed on three levels: eye (mean value/eye), quadrant (highest quadrant value/eye), and blood vessel (highest blood vessel value/eye). RESULTS: Of 832 examinations (99 infants), 745 images (89.5\%) had 3-4 quadrants analyzable by ROPtool. On the eye level, ROPtool indices differed between eyes eventually treated versus not treated at PMA of 33-35 and 37 weeks for TI, SAI, and TWP, and at PMA of 33-34 and 37 weeks for DI (P <= 0.0014), and change per week differed between eyes eventually treated versus not treated only for SAI at PMA of 32 weeks (P \&lt; 0.001). CONCLUSIONS: Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32 weeks PMA. ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.08.015},
	author = {Hong, Gloria J and Koerner, Jagger C and Weinert, Marguerite C and Stinnett, Sandra S and Freedman, Sharon F and Wallace, David K and Riggins, J Wayne and Gallaher, Keith J and Prakalapakorn, S Grace}
}
@article {416896,
	title = {Corvis ST Tonometer for Measuring Postoperative IOP in LASIK Patients.},
	journal = {Optom Vis Sci},
	volume = {92},
	number = {5},
	year = {2015},
	month = {2015 May},
	pages = {589-95},
	abstract = {PURPOSE: To compare the postoperative measurements of intraocular pressure (IOP) using the Corvis ST Tonometer (CST), ocular response analyzer (ORA), and Goldmann applanation tonometry (GAT) in eyes undergoing laser in situ keratomileusis (LASIK), as well as to analyze the relationship between the corneal biomechanical parameters of the CST and the ORA. METHODS: Fifty participants who had undergone LASIK to treat myopia in the previous 3 months were enrolled. Postoperative IOP measurements of these participants were obtained using the CST, ORA (corneal-compensated IOP [IOPcc], Goldmann-correlated IOP [IOPg]), and GAT. Device agreement was calculated by Bland-Altman analysis. The metrics of corneal biomechanical properties were recorded using the ORA and the CST. Corneal biomechanical parameters were compared. RESULTS: The Bland-Altman analysis revealed a significant bias between CST and GAT, between CST and IOPcc, and between CST and IOPg of 3.4, 1.0, and 3.8, mm Hg, respectively, with 95\% limits of agreement of -0.7 to 7.5 mm Hg, -2.1 to 4.2 mm Hg, and -0.4 to 8.0 mm Hg. The ORA-derived IOP measurements, CST-derived IOP, and GAT IOP values showed good correlation with each other. The CST IOP and IOPcc were higher than the GAT IOP (all p \&lt; 0.05), whereas IOPg did not differ from the GAT IOP readings. Ocular response analyzer-derived corneal biomechanical parameters (corneal hysteresis and the corneal resistance factor) showed significant correlations with CST-derived parameters, including the maximum deformation amplitude at the corneal apex and the time from start until the first applanation. CONCLUSIONS: The CST offers an alternative method for measuring postoperative IOP in LASIK patients, and it appears to obtain higher IOP values than other tonometry techniques. The technique may facilitate the investigation of corneal biomechanical property changes in LASIK-treated eyes.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000000575},
	author = {Hong, Jiaxu and Yu, Zhiqiang and Jiang, Chunhui and Zhou, Xingtao and Liu, Zuguo and Sun, Xinghuai and Xu, Jianjiang}
}
@article {1354345,
	title = {Evaluation of age-related changes in noninvasive tear breakup time},
	journal = {Optom Vis Sci},
	volume = {91},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {150-5},
	abstract = {PURPOSE: To establish normal noninvasive tear film breakup time (NI-BUT) values in the Chinese population and investigate age-related changes in NI-BUT using a newly developed Keratograph. METHODS: Forty normal volunteers with a mean age of 32.8 {\textpm} 16.7 years were recruited for this study. Clinical and demographic data, including age, gender, fluorescein tear film breakup time (FBUT), and Schirmer I test values were collected from the subjects. Noninvasive tear film breakup time was measured using a new method based on a corneal topographer equipped with a modified scan software. The correlations between the NI-BUT, age, and gender were determined. RESULTS: In total, a significant difference between the NI-BUT and the FBUT was found (4.9 {\textpm} 2.4 seconds vs. 9.0 {\textpm} 3.0 seconds; p \&lt; 0.001). No statistically significant difference in the NI-BUT was observed between the male and female subjects (5.5 {\textpm} 2.0 seconds vs. 4.5 {\textpm} 2.5 seconds; p = 0.137). In addition, no significant correlation was detected between the NI-BUT and age (0.143, p = 0.321). CONCLUSIONS: The NI-BUT values found in this study are much lower than those of previous reports. Our results show no significant differences in tear film stability with age. The tear physiology of the Chinese population may not be the same as in Western populations.},
	keywords = {Adolescent, Adult, Aged, Aging, Female, Fluorescein, Humans, Male, Middle Aged, Optometry, Reference Values, Tears, Young Adult},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000000126},
	author = {Hong, Jiaxu and Liu, Zuguo and Hua, Jing and Wei, Anji and Xue, Feng and Yang, Yujing and Sun, Xinghuai and Xu, Jianjiang}
}
@article {836861,
	title = {Nasolacrimal recanalization as an alternative to external dacryocystorhinostomy for treating failed nasolacrimal duct intubation.},
	journal = {Medicine (Baltimore)},
	volume = {95},
	number = {30},
	year = {2016},
	month = {2016 Jul},
	pages = {e4350},
	abstract = {To compare the surgical duration and clinical outcomes of nasolacrimal recanalization versus external dacryocystorhinostomy (DCR) in the treatment of failed nasolacrimal duct intubation.This is a retrospective, comparative, and interventional study. We evaluated the outcomes of 66 consecutive patients undergoing either nasolacrimal recanalization (n = 32) or DCR (n = 34) in a tertiary lacrimal disease referral center. Length of surgical duration, clinical outcomes, and rate of recurrence at 18 months postoperatively were compared.The mean surgical duration was 18.5 minutes (range, 15-25 minutes) for nasolacrimal recanalization and 48.2 minutes (range, 45-61 minutes) for DCR, respectively (P \&lt; 0.001). The rate of success was 84.4\% in the recanalization group and 85.3\% in the DCR group, respectively (P = 0.91). The time to recurrence was 2.6 {\textpm} 1.1 months in the recanalization group and 5.6 {\textpm} 2.1 months in the DCR group (P \&lt; 0.001). Five failed cases in each group received a secondary DCR surgery with the same resolution rate (40\%). The absence of ocular discharge at baseline was a significant predictor for a successful outcome in the recanalization group (P = 0.04) but not in the DCR group (P = 0.63).Nasolacrimal recanalization is an effective, safe, and time-saving alternative to DCR for the treatment of failed nasolacrimal duct intubation. Clinicians should be cautious in patients with discharge.},
	issn = {1536-5964},
	doi = {10.1097/MD.0000000000004350},
	author = {Hong, Jiaxu and Qian, Tingting and Wei, Anji and Sun, Zhongmou and Wu, Dan and Chen, Yihe and Marmalidou, Anna and Lu, Yi and Sun, Xinghuai and Liu, Zuguo and Amparo, Francisco and Xu, Jianjiang}
}
@article {913481,
	title = {Optimising keratoplasty for Peters{\textquoteright} anomaly in infants using spectral-domain optical coherence tomography},
	journal = {Br J Ophthalmol},
	volume = {101},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {820-827},
	abstract = {PURPOSE: To present in vivo anterior segment optical coherence tomography (OCT) features of infants with Peters{\textquoteright} anomaly obtained during presurgical examination under general anaesthesia, and to evaluate the impact of OCT features on surgical decision making. METHODS: This is a single-centre, consecutive, observational case series including 44 eyes of 27 infants with Peters{\textquoteright} anomaly (5-18 months) undergoing keratoplasty. Medical records of patients were reviewed retrospectively. Clinical features and OCT findings, along with their impact on surgical decision-making were analysed. RESULTS: Of 27 patients, 10 had unilateral and 17 had bilateral disease. Two patients with mild disease (three eyes) had a posterior corneal defect with leukoma (2/27, 7.4\%). Twenty patients (32 eyes) with iridocorneal adhesions were classified as having moderate Peters{\textquoteright} anomaly (20/27, 74.1\%) and five patients (nine eyes) with lenticulocorneal adhesions were classified as having severe Peters{\textquoteright} anomaly (5/27, 18.5\%). The range of angle closure, anterior chamber depth and maximum iridocorneal adhesion length (all p\&lt;0.001) were significantly different among groups, indicating that they might serve as novel OCT parameters for assessing the severity of Peters{\textquoteright} anomaly. The surgical approach in seven patients (21.2\%) was altered in response to intraoperative OCT findings, which provided information regarding the anatomical structure of the anterior chamber not provided by the surgical microscope. The use of OCT prevented unnecessary cataract surgeries in five patients. CONCLUSIONS: Our study showed that information gained from OCT under anaesthesia allows surgeons to classify type and severity of Peters{\textquoteright} anomaly and supports surgical decision making.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2016-308658},
	author = {Hong, Jiaxu and Yang, Yujing and Cursiefen, Claus and Mashaghi, Alireza and Wu, Dan and Liu, Zuguo and Sun, Xinghuai and Dana, Reza and Xu, Jianjiang}
}
@article {1653597,
	title = {Beyond the Cane: Describing Urban Scenes to Blind People for Mobility Tasks},
	journal = {ACM Trans Access Comput},
	volume = {15},
	number = {3},
	year = {2022},
	month = {2022 Sep},
	abstract = {Blind people face difficulties with independent mobility, impacting employment prospects, social inclusion, and quality of life. Given the advancements in computer vision, with more efficient and effective automated information extraction from visual scenes, it is important to determine what information is worth conveying to blind travelers, especially since people have a limited capacity to receive and process sensory information. We aimed to investigate which objects in a street scene are useful to describe and how those objects should be described. Thirteen cane-using participants, five of whom were early blind, took part in two urban walking experiments. In the first experiment, participants were asked to voice their information needs in the form of questions to the experimenter. In the second experiment, participants were asked to score scene descriptions and navigation instructions, provided by the experimenter, in terms of their usefulness. The descriptions included a variety of objects with various annotations per object. Additionally, we asked participants to rank order the objects and the different descriptions per object in terms of priority and explain why the provided information is or is not useful to them. The results reveal differences between early and late blind participants. Late blind participants requested information more frequently and prioritized information about objects{\textquoteright} locations. Our results illustrate how different factors, such as the level of detail, relative position, and what type of information is provided when describing an object, affected the usefulness of scene descriptions. Participants explained how they (indirectly) used information, but they were frequently unable to explain their ratings. The results distinguish between various types of travel information, underscore the importance of featuring these types at multiple levels of abstraction, and highlight gaps in current understanding of travel information needs. Elucidating the information needs of blind travelers is critical for the development of more useful assistive technologies.},
	issn = {1936-7228},
	doi = {10.1145/3522757},
	author = {Hoogsteen, Karst M P and Szpiro, Sarit and Kreiman, Gabriel and Peli, Eli}
}
@article {1806496,
	title = {The Role of Complement Dysregulation in Glaucoma},
	journal = {Int J Mol Sci},
	volume = {25},
	number = {4},
	year = {2024},
	month = {2024 Feb 15},
	abstract = {Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of glaucoma is not well understood, emerging evidence suggests that dysregulation of the complement system, a key component of innate immunity, plays a crucial role. In glaucoma, dysregulation of the complement cascade and impaired regulation of complement factors contribute to chronic inflammation and neurodegeneration. Complement components such as C1Q, C3, and the membrane attack complex have been implicated in glaucomatous neuroinflammation and retinal ganglion cell death. This review will provide a summary of human and experimental studies that document the dysregulation of the complement system observed in glaucoma patients and animal models of glaucoma driving chronic inflammation and neurodegeneration. Understanding how complement-mediated damage contributes to glaucoma will provide opportunities for new therapies.},
	keywords = {Animals, Complement System Proteins, Disease Models, Animal, Glaucoma, Humans, Inflammation, Neurodegenerative Diseases, Retinal Ganglion Cells},
	issn = {1422-0067},
	doi = {10.3390/ijms25042307},
	author = {Hoppe, Cindy and Gregory-Ksander, Meredith}
}
@article {1498249,
	title = {Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy, Third Edition},
	journal = {Telemed J E Health},
	volume = {26},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {495-543},
	abstract = {Contributors The following document and appendices represent the third edition of the . These guidelines were developed by the Diabetic Retinopathy Telehealth Practice Guidelines Working Group. This working group consisted of a large number of subject matter experts in clinical applications for telehealth in ophthalmology. The editorial committee consisted of Mark B. Horton, OD, MD, who served as working group chair and Christopher J. Brady, MD, MHS, and Jerry Cavallerano, OD, PhD, who served as cochairs. The writing committees were separated into seven different categories. They are as follows: 1.Clinical/operational: Jerry Cavallerano, OD, PhD (Chair), Gail Barker, PhD, MBA, Christopher J. Brady, MD, MHS, Yao Liu, MD, MS, Siddarth Rathi, MD, MBA, Veeral Sheth, MD, MBA, Paolo Silva, MD, and Ingrid Zimmer-Galler, MD. 2.Equipment: Veeral Sheth, MD (Chair), Mark B. Horton, OD, MD, Siddarth Rathi, MD, MBA, Paolo Silva, MD, and Kristen Stebbins, MSPH. 3.Quality assurance: Mark B. Horton, OD, MD (Chair), Seema Garg, MD, PhD, Yao Liu, MD, MS, and Ingrid Zimmer-Galler, MD. 4.Glaucoma: Yao Liu, MD, MS (Chair) and Siddarth Rathi, MD, MBA. 5.Retinopathy of prematurity: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD. 6.Age-related macular degeneration: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD. 7.Autonomous and computer assisted detection, classification and diagnosis of diabetic retinopathy: Michael Abramoff, MD, PhD (Chair), Michael F. Chiang, MD, and Paolo Silva, MD.},
	issn = {1556-3669},
	doi = {10.1089/tmj.2020.0006},
	author = {Horton, Mark B and Brady, Christopher J and Cavallerano, Jerry and Abramoff, Michael and Barker, Gail and Chiang, Michael F and Crockett, Charlene H and Garg, Seema and Karth, Peter and Liu, Yao and Newman, Clark D and Rathi, Siddarth and Sheth, Veeral and Silva, Paolo and Stebbins, Kristen and Zimmer-Galler, Ingrid}
}
@article {959416,
	title = {Clinical Components of Telemedicine Programs for Diabetic Retinopathy.},
	journal = {Curr Diab Rep},
	volume = {16},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {129},
	abstract = {Diabetic retinopathy is a leading cause of new-onset vision loss worldwide. Treatments supported by large clinical trials are effective in preserving vision, but many persons do not receive timely diagnosis and treatment of diabetic retinopathy, which is typically asymptomatic when most treatable. Telemedicine evaluation to identify diabetic retinopathy has the potential to improve access to care, but there are no universal standards regarding camera choice or protocol for ocular telemedicine. We review the literature regarding the impact of imaging device, number and size of retinal images, pupil dilation, type of image grader, and diagnostic accuracy on telemedicine assessment for diabetic retinopathy. Telemedicine assessment of diabetic retinopathy has the potential to preserve vision, but further development of telemedicine specific technology and standardization of operations are needed to better realize its potential.},
	issn = {1539-0829},
	doi = {10.1007/s11892-016-0813-8},
	author = {Horton, Mark B and Silva, Paolo S and Cavallerano, Jerry D and Aiello, Lloyd Paul}
}
@article {959421,
	title = {Operational Components of Telemedicine Programs for Diabetic Retinopathy.},
	journal = {Curr Diab Rep},
	volume = {16},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {128},
	abstract = {Diabetic retinopathy is a leading cause of new-onset vision loss worldwide. Treatments supported by large clinical trials are effective in preserving vision, but many persons do not receive timely diagnosis and treatment of diabetic retinopathy, which is typically asymptomatic when most treatable. Telemedicine evaluation to identify diabetic retinopathy has the potential to improve access to care and improve outcomes, but incomplete implementation of published standards creates a risk to program utility and sustainability. In a prior article, we reviewed the literature regarding the impact of imaging device, number and size of retinal images, pupil dilation, type of image grader, and diagnostic accuracy on telemedicine assessment for diabetic retinopathy. This article reviews the literature regarding the impact of automated image grading, cost effectiveness, program standards, and quality assurance (QA) on telemedicine assessment of diabetic retinopathy. Telemedicine assessment of diabetic retinopathy has the potential to preserve vision, but greater attention to development and implementation of standards is needed to better realize its potential.},
	issn = {1539-0829},
	doi = {10.1007/s11892-016-0814-7},
	author = {Horton, Mark B and Silva, Paolo S and Cavallerano, Jerry D and Aiello, Lloyd Paul}
}
@article {1328886,
	title = {Patching retinal breaks with polyethylene glycol-based synthetic hydrogel sealant for retinal detachment in rabbits},
	journal = {Exp Eye Res},
	volume = {177},
	year = {2018},
	month = {2018 Dec},
	pages = {117-121},
	abstract = {The purpose of this study was to evaluate absorbable polyethylene glycol (PEG)-based synthetic hydrogel as a sealant for retinal breaks in rhegmatogenous retinal detachment (RD). A three-port, 25-gauge vitrectomy was performed on nine Dutch pigmented rabbit eyes. Subsequently, RD was induced by creating a retinal break. The retina was then reattached by fluid-air exchange. In six of nine eyes (RD-PEG group), PEG sealant was applied to completely cover the retinal breaks, and then photopolymerized with light; thereafter, intravitreous air was replaced with balanced salt solution (BSS). In the remaining three eyes (RD group), PEG sealant was not applied, but the intravitreous air was replaced with BSS. Ophthalmological examinations and intraocular pressure measurements were conducted preoperatively, and at 1 and 7 days, and 1, 3, and 6 months postoperatively. Histological examinations of the eyes were performed after 6 postoperative months. At surgery, retinal reattachment with PEG sealant was achieved in all eyes in the RD-PEG group. Fundoscopic and optical coherence tomographic examinations revealed that the retina remained attached in all the eyes of the RD-PEG group throughout the 6-month observation period. Histological examination revealed no signs of damage in the retinal layers at the edges of the retinal breaks that were in contact with the sealant. In the RD group, the retinas detached in all eyes within 7 days postoperatively. The PEG sealant closed the retinal breaks and maintained retinal reattachment. Intraocular tamponade was not necessary.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.08.004},
	author = {Hoshi, Sujin and Okamoto, Fumiki and Arai, Mikki and Hirose, Tatsuo and Sugiura, Yoshimi and Murakami, Tomoya and Oshika, Tetsuro}
}
@article {503986,
	title = {In Vivo and In Vitro Feasibility Studies of Intraocular Use of Polyethylene Glycol-Based Synthetic Sealant to Close Retinal Breaks in Porcine and Rabbit Eyes.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {8},
	year = {2015},
	month = {2015 Jul 1},
	pages = {4705-11},
	abstract = {PURPOSE: Absorbable polyethylene glycol-based synthetic sealant (PEG sealant) polymerizes under xenon illumination and forms a clear, flexible, and firmly adherent hydrogel. The intraocular biocompatibility of PEG sealant and efficacy for closing retinal breaks were evaluated. METHODS: In an in vitro study, retinal detachment with a tear was created in porcine eyecups after vitreous gel removal. Polyethylene glycol-based synthetic sealant was applied to cover the tear and polymerized with a 40-second application of xenon light. Retinal adhesion strength was tested by forcefully squirting balanced salt solution (BSS) onto the retinal tear. Polyethylene glycol-based synthetic sealant was soaked in the BSS, incubated at 37{\textdegree}C, and the pH measured periodically over 72 hours. In an in vivo study, PEG sealant was injected into the vitreous cavity of the left eyes of rabbits. Ophthalmologic examinations were performed and bilateral ERGs were recorded simultaneously before and 28 days after injection. The eyes were enucleated for histological evaluation. RESULTS: Adhesion of PEG sealant to the retina was good in BSS. A forceful squirt of BSS onto the retinal tear covered with PEG sealant did not detach the retina; the retinal tear without PEG sealant detached immediately. The pH of the BSS containing PEG sealant was between 7.2 and 8.2. No inflammatory reaction was observed in the eyes throughout 28 days of follow-up. The ERGs recorded before and after injection showed typical patterns. Histological examinations did not reveal any abnormality or inflammation. CONCLUSIONS: Polyethylene glycol-based synthetic sealant appeared to effectively seal retinal breaks and was not toxic to the eye.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15349},
	author = {Hoshi, Sujin and Okamoto, Fumiki and Arai, Mikki and Hirose, Tatsuo and Sugiura, Yoshimi and Kaji, Yuichi and Oshika, Tetsuro}
}
@article {1586161,
	title = {Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey},
	journal = {BMJ Open},
	volume = {11},
	number = {3},
	year = {2021},
	month = {2021 Mar 04},
	pages = {e039209},
	abstract = {OBJECTIVES: To compare sociodemographics and vision-related quality of life (QoL) of individuals with or without dry eye disease (DED); and to explore the impact of DED symptom severity on visual function, activity limitations and work productivity. DESIGN: Cross-sectional web-based survey. SETTING: General UK population. PARTICIPANTS: Adults >=18 years with (N=1002) or without (N=1003) self-reported DED recruited through email and screened. MAIN OUTCOME MEASURES: All participants completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), with six additional questions (items A3-A8), and the EuroQol 5 dimensions 5 levels. DED participants also completed Impact of Dry Eye on Everyday Life questionnaire, 5-item Dry Eye Questionnaire and the Standardised Patient Evaluation of Eye Dryness questionnaire along with the Ocular Comfort Index, Work Productivity and Activity Impairment and the Eye Dryness Score (EDS), a Visual Analogue Scale. RESULTS: Baseline demographic and clinical characteristics were similar in participants with versus without DED (mean age, 55.2 vs 55.0 years; 61.8\% vs 61.0\% women, respectively) based on recruitment targets. Scores were derived from NEI VFQ-25 using the new 28-item revised VFQ (VFQ-28R) scoring. Mean (SD) VFQ-28R scores were lower in participants with versus without DED, indicating worse functioning (activity limitations, 73.3 (12.3) vs 84.4 (12.3); socioemotional functioning, 75.3 (21.5) vs 90.3 (16.2); total score, 71.6 (12.8) vs 83.6 (12.6)). Higher percentages of problems/inability to do activities were observed among those with versus without DED. The impact of DED on visual function was worse for participants with more severe DED symptoms, as assessed by EDS. In addition, a higher EDS was associated with worse symptoms on common DED scales and a worse impact on work productivity. CONCLUSIONS: DED symptoms were associated with negative effects on visual function, activities and work productivity, whereas worse DED symptoms had a greater impact on vision-related QoL and work productivity.},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2020-039209},
	author = {Hossain, Parwez and Siffel, Csaba and Joseph, Corey and Meunier, Juliette and Markowitz, Jessica T and Dana, Reza}
}
@article {1773571,
	title = {Categorization of a Universal Coding System to Distinguish Use of Durable Medical Equipment and Supplies in Pediatric Patients},
	journal = {JAMA Netw Open},
	volume = {6},
	number = {10},
	year = {2023},
	month = {2023 Oct 02},
	pages = {e2339449},
	abstract = {IMPORTANCE: Although durable medical equipment and supplies (DMES) are commonly used to optimize the health and function in pediatric patients, little is known about the prevalence of use and spending on DMES. OBJECTIVE: To categorize the Healthcare Common Procedure Coding System (HCPCS) for distinguishing DMES types, and to measure the prevalence and related spending of DMES in pediatric patients using Medicaid. DESIGN, SETTING, AND PARTICIPANTS: This study is a cross-sectional analysis of the 2018 Merative Medicaid Database and included 4 569 473 pediatric patients aged 0 to 21 years enrolled in Medicaid in 12 US states from January 1 to December 31, 2018. Data were analyzed from February 2019 to April 2023. EXPOSURE: DMES exposure was identified with the Centers for Medicare \&amp; Medicaid Services HCPCS codes. Three pediatricians categorized HCPCS DMES codes submitted by vendors for reimbursement of dispensed DMES into DMES types and end-organ systems; 15 expert reviewers refined the categorization (2576 DMES codes, 164 DMES types, 14 organ systems). MAIN OUTCOMES AND MEASURES: The main outcome was DMES prevalence \&amp; Medicaid spending. The χ2 test was used to compare DMES prevalence and Wilcoxon rank sum tests were used to compare per-member-per-year (PMPY) spending by complex chronic conditions (CCC). RESULTS: Of the 4 569 473 patients in the study cohort, 49.3\% were female and 56.1\% were aged 5 to 15 years. Patients used 133 of 164 (81.1\%) DMES types. The DMES prevalence was 17.1\% (95\% CI, 17.0\%-17.2\%) ranging from 10.1\% (95\% CI, 10.0\%-10.2\%) in patients with no chronic condition to 60.9\% (95\% CI, 60.8\%-61.0\%) for patients with 2 or more CCCs. The PMPY DMES spending was $593, ranging from $349 for no chronic condition to $4253 for 2 or more CCCs. Lens (7.9\%), vision frames (6.2\%), and orthotics for orthopedic injury (0.8\%) were the most common DME in patients with no chronic condition. Enteral tube / feeding supplies (19.8\%), diapers (19.2\%), lower extremity orthotics (12.3\%), wheelchair (9.6\%), oxygen (9.0\%), and urinary catheter equipment (4.2\%) were among the most common DMES in children with 2 or more CCCs. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, HCPCS distinguished a variety of DME types and use across pediatric populations. Further investigation should assess the utility of the HCPCS DMES categorization with efforts to optimize the quality and safety of DMES use.},
	keywords = {Aged, Child, Chronic Disease, Cross-Sectional Studies, Durable Medical Equipment, Female, Humans, Male, Medicaid, Medicare, United States},
	issn = {2574-3805},
	doi = {10.1001/jamanetworkopen.2023.39449},
	author = {Hotz, Arda and Sprecher, Eli and Bastianelli, Lucia and Rodean, Jonathan and Stringfellow, Isabel and Barkoudah, Elizabeth and Cohen, Laurie E and Estrada, Carlos and Graham, Robert and Greenwood, Jonathan and Kyle, Jennifer and Mann, Nina and Pinkham, Maria and Solari, Toni and Rosen, Rachel and Saleeb, Susan and Shah, Ankoor S and Watters, Karen and Wells, Sarah and Berry, Jay G}
}
@article {1354346,
	title = {The inhibitory effect of IFN-γ on protease HTRA1 expression in rheumatoid arthritis},
	journal = {J Immunol},
	volume = {193},
	number = {1},
	year = {2014},
	month = {2014 Jul 01},
	pages = {130-8},
	abstract = {The high temperature requirement A1 (HTRA1) is a potent protease involved in many diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms that control HTRA1 expression need to be determined. In this study, we demonstrated that IFN-γ significantly inhibited the basal and LPS-induced HTRA1 expression in fibroblasts and macrophages, which are two major cells for HTRA1 production in RA. Importantly, the inhibitory effect of IFN-γ on HTRA1 expression was evidenced in collagen-induced arthritis (CIA) mouse models and in human RA synovial cells. In parallel with the enhanced CIA incidence and pathological changes in IFN-γ-deficient mice, HTRA1 expression in the joint tissues was also increased as determined by real-time PCR and Western blots. IFN-γ deficiency increased the incidence of CIA and the pathological severity in mice. Neutralization of HTRA1 by Ab significantly reversed the enhanced CIA frequency and severity in IFN-γ-deficient mice. Mechanistically, IFN-γ negatively controls HTRA1 expression through activation of p38 MAPK/STAT1 pathway. Dual luciferase reporter assay and chromatin immunoprecipitation analysis showed that STAT1 could directly bind to HTRA1 promoter after IFN-γ stimulation. This study offers new insights into the molecular regulation of HTRA1 expression and its role in RA pathogenesis, which may have significant impact on clinical therapy for RA and possibly other HTRA1-related diseases, including osteoarthritis, age-related macular degeneration, and cancer.},
	keywords = {Animals, Arthritis, Rheumatoid, Cell Line, Collagen, Disease Models, Animal, Gene Expression Regulation, Enzymologic, High-Temperature Requirement A Serine Peptidase 1, Humans, Interferon-gamma, Joints, Lipopolysaccharides, Mice, Mice, Knockout, p38 Mitogen-Activated Protein Kinases, Promoter Regions, Genetic, Serine Endopeptidases, STAT1 Transcription Factor},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1302700},
	author = {Hou, Yuzhu and Lin, Haijiang and Zhu, Linnan and Liu, Zhaoting and Hu, Fanlei and Shi, Jianfeng and Yang, Tao and Shi, Xiaoyun and Guo, Huifang and Tan, Xiaotian and Zhang, Lianfeng and Wang, Qiang and Li, Zhanguo and Zhao, Yong}
}
@article {468936,
	title = {Asymmetry in the Collision Judgments of People With Homonymous Field Defects and Left Hemispatial Neglect.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {6},
	year = {2015},
	month = {2015 Jun 1},
	pages = {4135-42},
	abstract = {PURPOSE: Although the impact of homonymous visual field defects (HFDs) on mobility has been investigated previously, the emphasis has been on obstacle detection. Relatively little is known about HFD patients{\textquoteright} ability to judge collisions once an obstacle is detected. We investigated this using a walking simulator. METHODS: Patients with HFDs (n = 29) and subjects with normal vision (NV; n = 21) were seated in front of a large screen on which a visual simulation of walking was displayed. They made collision judgments for a human figure that appeared for 1 second at lateral offsets from the virtual walking path. A perceived-collision threshold was calculated for right and left sides. RESULTS: Symmetrical collision thresholds (same on left and right sides) were measured for participants with NV (n = 21), and right (n = 9) and left (n = 7) HFD without hemispatial neglect. Participants with left neglect (n = 10) showed significant asymmetry with thresholds smaller (compared to the NV group and other HFD groups) on the blind (P \&lt; 0.001) and larger on the seeing (P = 0.05) sides. Despite the asymmetry, the overall width of the zone of perceived collision risk was not different, suggesting a relatively uniform rightward deviation in judgments of the left neglect group. CONCLUSIONS: Left neglect was associated with rightward asymmetry in collision judgments, which may cause collisions on the left side even when an obstacle is detected. These behaviors may represent the spatial misperceptions in body midline described previously in patients with left neglect.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15492},
	author = {Houston, Kevin E and Woods, Russell L and Goldstein, Robert B and Peli, Eli and Luo, Gang and Bowers, Alex R}
}
@article {882936,
	title = {Patching for Diplopia Contraindicated in Patients with Brain Injury?},
	journal = {Optom Vis Sci},
	volume = {94},
	number = {1},
	year = {2017},
	pages = {120-124},
	abstract = {PURPOSE: Patching for double vision is a common palliative treatment for head-trauma patients with acquired strabismus when prisms are not feasible. METHODS: We review literature on spatial neglect and discuss possible effects of monocular occlusion on spatial attention. RESULTS: Patching the left eye has been shown to worsen spatial judgments in some brain-injured patients with left neglect by inhibiting the right superior colliculus further impairing contralateral leftward orienting (the Sprague Effect). CONCLUSIONS: Because more peripheral parts of the visual field increasingly project to the contralateral superior colliculus with the temporal crescent being entirely contralateral, avoiding patching of the temporal crescent was advised, and in most cases can be achieved by taping off the spectacle lens and avoiding an elastic eye patch.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000000976},
	author = {Houston, Kevin E and Barrett, A M}
}
@article {1295866,
	title = {Driving With Hemianopia VI: Peripheral Prisms and Perceptual-Motor Training Improve Detection in a Driving Simulator},
	journal = {Transl Vis Sci Technol},
	volume = {7},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {5},
	abstract = {Purpose: Drivers with homonymous hemianopia (HH) were previously found to have impaired detection of blind-side hazards, yet in many jurisdictions they may obtain a license. We evaluated whether oblique 57Δ peripheral prisms (p-prisms) and perceptual-motor training improved blind-side detection rates. Methods: Patients with HH (n = 11) wore p-prisms for 2 weeks and then received perceptual-motor training (six visits) detecting and touching stimuli in the prism-expanded vision. In a driving simulator, patients drove and pressed the horn upon detection of pedestrians who ran toward the roadway (26 from each side): (1) without p-prisms at baseline; (2) with p-prisms after 2 weeks acclimation but before training; (3) with p-prisms after training; and (4) 3 months later. Results: P-prisms improved blind-side detection from 42\% to 56\%, which further improved after training to 72\% (all P \&lt; 0.001). Blind-side timely responses (adequate time to have stopped) improved from 31\% without to 44\% with p-prisms (P \&lt; 0.001) and further improved with training to 55\% (P = 0.02). At the 3-month follow-up, improvements from training were maintained for detection (65\%; P = 0.02) but not timely responses (P = 0.725). There was wide between-subject variability in baseline detection performance and response to p-prisms. There were no negative effects of p-prisms on vehicle control or seeing-side performance. Conclusions: P-prisms improved detection with no negative effects, and training may provide additional benefit. Translational Relevance: In jurisdictions where people with HH are legally driving, these data aid in clinical decision making by providing evidence that p-prisms improve performance without negative effects.},
	issn = {2164-2591},
	doi = {10.1167/tvst.7.1.5},
	author = {Houston, Kevin E and Peli, Eli and Goldstein, Robert B and Bowers, Alex R}
}
@article {1328887,
	title = {Peripheral Prisms Improve Obstacle Detection during Simulated Walking for Patients with Left Hemispatial Neglect and Hemianopia},
	journal = {Optom Vis Sci},
	volume = {95},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {795-804},
	abstract = {SIGNIFICANCE: The first report on the use of peripheral prisms (p-prisms) for patients with left neglect and homonymous visual field defects (HVFDs). PURPOSE: The purpose of this study was to investigate if patients with left hemispatial neglect and HVFDs benefit from p-prisms to expand the visual field and improve obstacle detection. METHODS: Patients (24 with HVFDs, 10 of whom had left neglect) viewed an animated, virtual, shopping mall corridor and reported if they would have collided with a human obstacle that appeared at various offsets up to 13.5{\textdegree} from their simulated walking path. There were 40 obstacle presentations on each side, with and without p-prisms. No training with p-prisms was provided, and gaze was fixed at the center of expansion. RESULTS: Detection on the side of the HVFD improved significantly with p-prisms in both groups, from 26 to 92\% in the left-neglect group and 43 to 98\% in the non-neglect group (both P \&lt; .001). There was a tendency for greater improvement in the neglect patients with p-prisms. For collision judgments, both groups exhibited a large increase in perceived collisions on the side of the HVFD with the prisms (P \&lt; .001), with no difference between the groups (P = .93). Increased perceived collisions represent a wider perceived safety margin on the side of the HVFD. CONCLUSIONS: Within the controlled conditions of this simulated, collision judgment task, patients with left neglect responded well to initial application of p-prisms exhibiting improved detection and wider safety margins on the side of the HVFD that did not differ from non-neglect patients. Further study of p-prisms for neglect patients in free-gaze conditions after extended wear and in real-world mobility tasks is clearly warranted.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001280},
	author = {Houston, Kevin E and Bowers, Alex R and Peli, Eli and Woods, Russell L}
}
@article {882941,
	title = {Restoration of Vision After Brain Injury Using Magnet Glasses},
	journal = {Am J Phys Med Rehabil},
	volume = {96},
	number = {4},
	year = {2017},
	month = {2017 Apr},
	pages = {e70-e74},
	abstract = {Visual impairments are common after traumatic brain injury (TBI) and negatively affect quality of life. We describe a 39-year-old woman with a severe TBI who was evaluated by the inpatient optometry and vision rehabilitation service with findings of complete right homonymous hemianopia and right cranial nerve III palsy with 30-degree right exotropia (eye turn out) and complete right ptosis (eyelid will not open). The 30-degree exotropia advantageously generated 30 degrees of right visual field expansion when the right ptosis was treated with a magnetic levator prosthesis, which restores eyelid opening. Once opened, the patient used visual field expansion derived from a right exotropia to overcome functional impairments caused by right hemianopia. Field expansion improved the patient{\textquoteright}s wheelchair mobility and reaching tasks during inpatient therapy. This is the first report of visual field expansion by strabismus facilitated by correction of ptosis. Strabismus should be considered for its potential field expansion benefits when homonymous visual deficits are present, before considering patching. A multidisciplinary vision rehabilitation team is well suited to make this determination.},
	issn = {1537-7385},
	doi = {10.1097/PHM.0000000000000592},
	author = {Houston, Kevin E and Paschalis, Eleftherios I and Angueira, Danielle C and Bronstad, P Matthew and Barrett, Anna M and Iaccarino, Mary Alexis}
}
@article {1677771,
	title = {Development and 5-year Evaluation of Diagnosis-Specific Protocols for Visual Neuro-Rehabilitation in a Multicenter Inpatient Rehabilitation Network},
	journal = {Arch Rehabil Res Clin Transl},
	volume = {5},
	number = {1},
	year = {2023},
	month = {2023 Mar},
	pages = {100246},
	abstract = {OBJECTIVE: To provide a retrospective evaluation of a new eye and vision rehabilitation care pathway in a U.S. multi-site inpatient rehabilitation network involving the occupational therapy (OT) staff and a consulting doctor of optometry (OD) specializing in vision rehabilitation. DESIGN: Retrospective study. SETTING: Two Inpatient Rehabilitation Facilities (IRFs) and 1 Long Term Acute Care Hospital (LTACH). PARTICIPANTS: There were 2083 records reviewed (44\% women, avg. age 59 years). The most common diagnoses were hemispatial neglect (19.2\%), homonymous field defects (18.5\%), and oculomotor cranial nerve palsies (16.7\%) (N=2083). INTERVENTIONS: Clinical care was reviewed where diagnosis-specific protocols were developed and training was provided to OTs in order to reinforce OD-prescribed interventions during daily treatment sessions, including (1) third, fourth, and sixth ocular cranial nerve palsies (OCNPs) with prisms fitted for full time, postural adaptation training, and oculomotor re-education using pursuits, saccades, head-rotations, and binocular vision exercises including alternate cover and vergence; (2) homonymous hemianopia with training awareness of field loss, eccentric viewing, and fitting of Peli lens for optical field expansion; and (3) prism adaptation therapy (PAT) for left hemispatial neglect. MAIN OUTCOME MEASURES: Frequency of diagnoses. HYPOTHESIS: Diagnoses with developed protocols were most common. Secondarily, feasibility and efficacy by anonymous OT survey. RESULTS: 2083 vision consults were performed over 5 years. The most common diagnoses were hemispatial neglect (n=399, 19.2\%), homonymous field defects (n=386, 18.5\%), and OCNPs (n=347, 16.7\%). None of the OTs reported the protocols were infeasible and 63\% (IQR 38\%-69\%) reported their patients benefited from the interventions. The survey suggested prism for OCNPs helped in 42\%, and Peli lens and PAT both helped in 38\%. CONCLUSIONS: Data support the feasibility of this inpatient eye and vision rehabilitation care pathway which may be used as a foundation for creating or refining similar programs elsewhere. Uniform administration of IRF-based visual neuro-rehabilitation care could provide a substrate for future clinical trials to evaluate efficacy.},
	issn = {2590-1095},
	doi = {10.1016/j.arrct.2022.100246},
	author = {Houston, Kevin E and Keilty, Matthew and Collins, Caroline and Trehan, Ritika and Mouldovan, Talia and Stuckart, Kim and Engelhardt, Nancy and Nadeau, Melanie and Rovito, Craig A and Merabet, Lotfi B}
}
@article {1773591,
	title = {Clinical Report: Clinician Feedback on the Magnetic Levator Prosthesis},
	journal = {Optom Vis Sci},
	year = {2023},
	month = {2023 Oct 30},
	abstract = {SIGNIFICANCE: Stakeholder engagement has been identified by national health organizations as a crucial step to successful translation of new healthcare treatments. In this clinical report, clinician-stakeholder feedback is presented for the Magnetic Levator Prosthesis (MLP), a promising non-invasive spectacle device which restores eyelid motility with magnetic force. PURPOSE: To evaluate MLP clinical need and translational barriers. METHODS: Ten vision rehabilitation optometrists who attended an educational presentation on the MLP and participated in a hands-on workshop in the fitting of a patient were invited to complete an anonymous online survey. Ten multiple-choice items gathered data on estimated patient need, current approaches, main barriers for MLP, temporary versus chronic use, cost barriers, and need for insurance coverage. Open fields allowed for additional comments. RESULTS: Nine of 10 specialists completed the survey. Of those, 7 answered that they could potentially see at least 1-5 patients for ptosis management within a year. The most common ptosis management options reported were the ptosis crutch, taping the eyelid open, and Oxymetazoline drops, all with 6 responses each. Seven clinicians indicated that cost was a main concern. If cost-to-patient was not a barrier, all indicated they would be at least somewhat likely to try the MLP for: 1) temporary management of ptosis, 2) as a pre-surgical trial, and 3) for long term management of ptosis, with more selecting extremely likely and very likely than somewhat likely. Main comments were expressing enthusiasm for the technology and that it would be more appealing for patients if covered by insurance. CONCLUSIONS: This clinical report suggests the main barriers to clinical success of the MLP may be cost and insurance coverage, appearance of the device, and self-application. Possible solutions are cost-benefit analysis research, engineering efforts to reduce spectacle magnet size and improve the ease of eyelid magnet application.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000002080},
	author = {Houston, Kevin E and Nadeau, Melanie and Paschalis, Eleftherios I}
}
@article {1655720,
	title = {Feasibility of Magnetic Levator Prosthesis Frame Customization Using Craniofacial Scans and 3-D Printing},
	journal = {Transl Vis Sci Technol},
	volume = {11},
	number = {10},
	year = {2022},
	month = {2022 10 03},
	pages = {34},
	abstract = {Purpose: To determine the feasibility of a custom frame generation approach for nonsurgical management of severe blepharoptosis with the magnetic levator prosthesis (MLP). Methods: Participants (n = 8) with severe blepharoptosis (obscuring the visual axis) in one or both eyes who had previously been using a non-custom MLP had a craniofacial scan with a smartphone app to generate a custom MLP frame. A magnetic adhesive was attached to the affected eyelid. The custom MLP frame held a cylindrical magnet near the eyebrow above the affected eyelid, suspending it in the magnetic field while still allowing blinking. The spectacle magnet could be rotated manually, providing adjustable force via angular translation of the magnetic field. Fitting success and comfort were recorded, and interpalpebral fissure (IPF) was measured from video frames after 20 minutes in-office and one-week at-home use. Preference was documented, custom versus non-custom. Results: Overall, 88\% of patients (7/8) were successfully fitted with a median 9/10 comfort (interquartile 7-10) and median ptosis improvement of 2.3 mm (1.3-5.0); P = 0.01). Exact binomial testing suggested, with 80\% power, that the true population success rate was significantly greater than 45\% (P = 0.05). Five participants took the custom MLP home for one week, with only one case of mild conjunctival redness which resolved without treatment. Highest to lowest force modulation resulted in a marginally significant median IPF adjustment of 1.5 mm (0.8 to 2.7; P = 0.06). All preferred the custom frame. Conclusions: The three-dimensional custom MLP frame generation approach using a smartphone app-based craniofacial scan is a feasible approach for clinical deployment of the MLP. Translational Relevance: First demonstration of customized frame generation for the MLP.},
	keywords = {Artificial Limbs, Blepharoptosis, Feasibility Studies, Humans, Magnetic Phenomena, Oculomotor Muscles, Printing, Three-Dimensional},
	issn = {2164-2591},
	doi = {10.1167/tvst.11.10.34},
	author = {Houston, Kevin E and Paschalis, Eleftherios I}
}
@article {1125311,
	title = {Near Point of Convergence and Gait Deficits in Adolescents After Sport-Related Concussion},
	journal = {Clin J Sport Med},
	volume = {28},
	number = {3},
	year = {2018},
	month = {2018 May},
	pages = {262-267},
	abstract = {OBJECTIVE: To prospectively examine gait characteristics of participants acutely after concussion with and without receded near point of convergence (NPC), compared with healthy controls.

DESIGN: Cross-sectional study.

SETTING: Sports-medicine clinic.

PARTICIPANTS: Patients examined after concussion (n = 33; mean {\textpm} SD = 7.2 {\textpm} 3.1 days) and a group of uninjured athletes (n = 31) completed a Postconcussion Symptom Scale, underwent NPC testing, and single/dual-task gait assessments.

INDEPENDENT VARIABLES: Near point of convergence was defined as the patient-reported diplopia distance when a fixation target moved toward the nose. Receded NPC was defined as a distance >5 cm from the tip of the nose.

MAIN OUTCOME MEASURES: Spatiotemporal gait characteristics in single-task and dual-task conditions were evaluated with analysis of variance; correlations were calculated between NPC and gait measures.

RESULTS: Eighteen of 33 (55\%) patients with concussion presented with receded NPC. Those with receded NPC exhibited slower gait speed (single-task = 1.06 {\textpm} 0.14 m/s vs 1.19 {\textpm} 0.15 m/s; dual-task = 0.80 {\textpm} 0.13 m/s vs 0.94 {\textpm} 0.13 m/s; P = 0.003) and shorter stride lengths (single-task = 1.11 {\textpm} 0.10 m vs 1.24 {\textpm} 0.11 m; dual-task = 0.97 {\textpm} 0.11 m vs 1.09 {\textpm} 0.11 m; P = 0.001) than healthy controls. Near point of convergence was moderately correlated with dual-task average walking speed for the normal NPC group (ρ = -0.56; P = 0.05). Postconcussion Symptom Scale scores did not significantly differ between groups (27 {\textpm} 18 vs 28 {\textpm} 16).

CONCLUSIONS: After concussion, adolescents with receded NPC exhibited significant gait-related deficits compared with healthy controls, whereas those with normal NPC did not. Vergence and gross motor system dysfunction may be associated after concussion. Gait and vergence measures may contribute useful information to postconcussion evaluations.},
	issn = {1536-3724},
	doi = {10.1097/JSM.0000000000000439},
	author = {Howell, David R and O'Brien, Michael J and Raghuram, Aparna and Shah, Ankoor S and Meehan, William P}
}
@article {1748456,
	title = {Identification of novel biomarkers for retinopathy of prematurity in preterm infants by use of innovative technologies and artificial intelligence},
	journal = {Prog Retin Eye Res},
	volume = {97},
	year = {2023},
	month = {2023 Nov},
	pages = {101208},
	abstract = {Retinopathy of prematurity (ROP) is a leading cause of preventable vision loss in preterm infants. While appropriate screening is crucial for early identification and treatment of ROP, current screening guidelines remain limited by inter-examiner variability in screening modalities, absence of local protocol for ROP screening in some settings, a paucity of resources and an increased survival of younger and smaller infants. This review summarizes the advancements and challenges of current innovative technologies, artificial intelligence (AI), and predictive biomarkers for the diagnosis and management of ROP. We provide a contemporary overview of AI-based models for detection of ROP, its severity, progression, and response to treatment. To address the transition from experimental settings to real-world clinical practice, challenges to the clinical implementation of AI for ROP are reviewed and potential solutions are proposed. The use of optical coherence tomography (OCT) and OCT angiography (OCTA) technology is also explored, providing evaluation of subclinical ROP characteristics that are often imperceptible on fundus examination. Furthermore, we explore several potential biomarkers to reduce the need for invasive procedures, to enhance diagnostic accuracy and treatment efficacy. Finally, we emphasize the need of a symbiotic integration of biologic and imaging biomarkers and AI in ROP screening, where the robustness of biomarkers in early disease detection is complemented by the predictive precision of AI algorithms.},
	keywords = {Algorithms, Artificial Intelligence, Humans, Infant, Infant, Newborn, Infant, Premature, Retinopathy of Prematurity, Vision Disorders},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2023.101208},
	author = {Hoyek, Sandra and da Cruz, Natasha F S and Patel, Nimesh A and Al-Khersan, Hasenin and Fan, Kenneth C and Berrocal, Audina M}
}
@article {1798346,
	title = {Anisocoria after vitrectomy and scleral buckle surgery in a patient with undifferentiated connective tissue disease},
	journal = {Indian J Ophthalmol},
	volume = {72},
	number = {Suppl 2},
	year = {2024},
	month = {2024 Feb 01},
	pages = {S161},
	keywords = {Anisocoria, Humans, Retinal Detachment, Retrospective Studies, Scleral Buckling, Treatment Outcome, Undifferentiated Connective Tissue Diseases, Vitrectomy},
	issn = {1998-3689},
	doi = {10.4103/IJO.IJO_2547_23},
	author = {Hoyek, Sandra and Kocasarac, Can and Chhablani, Jay}
}
@article {1647893,
	title = {Combined X-linked familial exudative vitreoretinopathy and retinopathy of prematurity phenotype in an infant with mosaic turner syndrome with ring X chromosome},
	journal = {Ophthalmic Genet},
	volume = {44},
	number = {2},
	year = {2023},
	month = {2023 Apr},
	pages = {198-203},
	abstract = {BACKGROUND: Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are two distinct pathologies of retinal angiogenesis with overlapping clinical features. METHODS: Examination, multimodal imaging, and genetic testing were used to guide diagnosis and treatment. RESULTS: We report a combined phenotype of X-linked FEVR and ROP in a 4-month-old girl with mosaic Turner syndrome with ring X chromosome born at 26 weeks gestational age. She was initially diagnosed with atypical ROP with a vitreous band causing a localized traction retinal detachment, inferotemporal to the macula in the right eye, vessels to posterior zone 2 with no clear ridge temporally in the left eye, and fluorescein leakage in both eyes. Due to the suspicion of concurrent FEVR, genetic testing using a vitreoretinopathy panel was performed which revealed a mosaic Turner syndrome associated with 45,X/46,X,r(X), subsequently confirmed by chromosome analysis. The deleted region in the ring X chromosome included the NDP and RS1 genes. The patient was treated with laser photocoagulation of the peripheral avascular retina and sub-Tenon{\textquoteright}s triamcinolone injection in both eyes, intravitreal injection of bevacizumab in the left eye, and pars plicata vitrectomy in the right eye. CONCLUSIONS: In premature neonates with atypical ROP, a clinical suspicion of concurrent FEVR or similar vasculopathy is important and genetic testing may elucidate a genetic etiology, which could influence management and prognosis. Turner syndrome can be connected with co-occurring Mendelian gene disorders, particularly in individuals with mosaicism. The concurrence of FEVR and ROP appears to result in atypical and possibly more severe phenotypes.},
	keywords = {Familial Exudative Vitreoretinopathies, Female, Humans, Infant, Newborn, Phenotype, Retinopathy of Prematurity, Turner Syndrome, X Chromosome},
	issn = {1744-5094},
	doi = {10.1080/13816810.2022.2098987},
	author = {Hoyek, Sandra and Wang, Marlene and Berrocal, Audina M and Wong, Ashley and Place, Emily M and Mason-Suares, Heather and Lin, Angela E and Mukai, Shizuo and Patel, Nimesh A}
}
@article {1798396,
	title = {Longitudinal Characteristics of Choroidal Neovascular Membrane in Pediatric Patients},
	journal = {Am J Ophthalmol},
	volume = {261},
	year = {2024},
	month = {2024 Jan 07},
	pages = {76-84},
	abstract = {PURPOSE: To report the clinical and imaging characteristics, including optical coherence tomography angiography (OCTA), and treatment outcomes of choroidal neovascular membranes (CNVMs) in children.

DESIGN: Retrospective clinical cohort study.

METHODS: Thirty eyes from 25 children (56\% girls) with CNVM from 2 centers were examined from 2005 to 2022. Clinical features, imaging findings, treatment regimens, and outcomes are described.

RESULTS: The most common causes of CNVM were idiopathic (48\%) and inflammatory (20\%). At diagnosis, most CNVMs were unilateral (80\%), active (83.3\%), and juxtafoveal (46.7\%). Twenty-five eyes (83.3\%) of 21 patients (84\%) were treated. The most common first-line treatment was intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) (92\%), with a retreatment rate of 52.2\% at an average of 237 days. The average number of total injections per eye was 2.3. Injections were safely administered in the clinic (52.2\%). A gain of 3 lines or 15 ETDRS (Early Treatment Diabetic Retinopathy Study) letters was observed at final visit. The average duration of follow-up was 56.46 {\textpm} 42.51 months. No ocular or systemic complication related to treatment was reported. Sixteen eyes (64\%) had OCTA images at both presentation and final visit, which showed a decrease in CNVM vessel density and vessel-length density, and in the height of retinal pigment epithelium detachment (RPED).

CONCLUSIONS: There are a variety of underlying etiologies for pediatric CNVMs, which are most often unilateral. Treatment with intravitreal anti-VEGF can be beneficial and does not often require frequent or chronic dosing. OCTA demonstrated a decrease in the CNVM vessel density and vessel-length density as well as in the height of RPED.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2024.01.004},
	author = {Hoyek, Sandra and Lu, Yifan and Mukai, Shizuo and Patel, Nimesh A}
}
@article {1761781,
	title = {Longitudinal Assessment of Macular Thickness and Microvascular Changes in Children with Sickle Cell Disease},
	journal = {Ophthalmol Retina},
	volume = {8},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {184-194},
	abstract = {PURPOSE: To longitudinally assess macular thickness and microvascular changes in children with sickle cell disease (SCD). DESIGN: A retrospective consecutive series. SUBJECTS: Children with SCD aged <= 18 years who had an ophthalmic examination at Boston Children{\textquoteright}s Hospital between January 1998 and August\&nbsp;2022. METHODS: Qualitative and quantitative analyses of both OCT and OCT angiography (OCTA) images were performed. MAIN OUTCOME MEASURES: Total retinal thickness measured on macular OCT, superficial capillary plexus and deep capillary plexus (DCP) vessel density (VD), and foveal avascular zone (FAZ) area measured on 6-\&nbsp;{\texttimes} 6-mm OCTA scans. RESULTS: International Classification of Diseases, 10th Revision, code search identified 303 pediatric SCD patients who underwent ophthalmic examination during the study period. OCT and OCTA images were acquired on 104 (17.2\%) and 60 (9.9\%) eyes at presentation and on 159 (26.2\%) and 100 (16.5\%) eyes at final visit, respectively. Overall, temporal retinal thinning was noted qualitatively in 35.6\% of SCD patients at presentation and 39.6\% at final visit. Of those patients with macular thinning, 94.6\% and 90.5\% had peripheral sickle cell retinopathy (SCR) at presentation and final visit. On quantitative OCT analysis, HbSS eyes had a lower retinal thickness in the fovea and temporal parafovea compared with HbSC (P \&lt; 0.05). Eyes with peripheral SCR had a larger FAZ at presentation compared with eyes without peripheral SCR (P\&nbsp;= 0.004), a lower DCP VD at final visit in the inferior temporal macula (P\&nbsp;= 0.03), and a higher DCP VD at final visit in the superior nasal macula (P\&nbsp;= 0.01). Eighty eyes of 40 patients had OCT, and 34 eyes of 20 patients had both OCT and OCTA images acquired at both initial and final visits. At final visit, retinal thickness decreased at the fovea, inferior perifovea, and temporal perifovea compared with presentation (P \&lt; 0.05). In parallel, VD DCP in the superonasal quadrant increased at final visit (P\&nbsp;= 0.03). CONCLUSIONS: Macular retinal thinning was progressive and observed in eyes with and without peripheral SCR. Over time, there was a compensatory increase in DCP VD in the nasal macula on OCTA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Anemia, Sickle Cell, Child, Fluorescein Angiography, Humans, Retinal Degeneration, Retinal Vessels, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.09.005},
	author = {Hoyek, Sandra and Lemire, Colin and Halawa, Omar and Altamirano-Lamarque, Francisco and Gonzalez, Efren and Patel, Nimesh A}
}
@article {1655704,
	title = {The Male to Female Ratio in Treatment-Warranted Retinopathy of Prematurity: A Systematic Review and Meta-analysis},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {11},
	year = {2022},
	month = {2022 Nov 01},
	pages = {1110-1120},
	abstract = {IMPORTANCE: Literature and anecdotal evidence suggest a relationship between male sex and retinopathy of prematurity (ROP). It is not known whether a difference, if present, is sex-related pathophysiologic predisposition or sex difference in meeting ROP screening criteria. OBJECTIVE: To evaluate the association of sex with the development of treatment-warranted ROP. DATA SOURCES: PubMed, Embase, and Web of Science databases were searched from 2000 to 2022. The search strategy used keywords including retinopathy of prematurity or ROP or retrolental fibroplasia and treatment or anti-VEGF or bevacizumab or ranibizumab or aflibercept or conbercept or laser or cryotherapy and gender or sex or male or female and medical subject headings terms. STUDY SELECTION: All studies reporting on treatment with anti-vascular endothelial growth factor, laser photocoagulation, and/or cryotherapy for ROP were identified. Studies reporting sex distribution in the treatment group were included in the meta-analysis. Exclusion criteria included case reports, case series of fewer than 10 treated patients, systematic reviews, conference abstracts, letters to the editor, animal studies, and non-English records. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened and extracted the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The proportions of treated male and female infants were combined using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Numbers and percentages of male and female infants treated for ROP. RESULTS: Of 11 368 identified studies, 316 met inclusion criteria, yielding a total of 31 026 treated patients. A higher percentage of male infants were treated for ROP (55\% [95\% CI, 0.54\%-0.55\%]), with low heterogeneity between studies (I2 = 34\%; P \&lt; .001). Thirty-eight studies reported sex distribution in the screened population (170 053 patients; 92 612 [53\%] male vs 77 441 [47\%] female). There was no significant difference in the odds of receiving treatment between screened male and female infants (pooled odds ratio, 1.04 [95\% CI, 0.91-1.18]; P = .67). CONCLUSIONS AND RELEVANCE: More male infants are treated for ROP than female infants. This could be due to a known relative pathophysiological fragility of preterm male infants in addition to a difference in ROP screening rates, with more male infants meeting the criteria than female infants. These findings have implications for future studies and may prompt more careful clinical monitoring of male neonates.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Female, Humans, Infant, Low Birth Weight, Infant, Newborn, Male, Ranibizumab, Retinopathy of Prematurity},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.3988},
	author = {Hoyek, Sandra and Peacker, Bryan L and Acaba-Berrocal, Luis A and Al-Khersan, Hasenin and Zhao, Yan and Hartnett, Mary Elizabeth and Berrocal, Audina M and Patel, Nimesh A}
}
@article {1642021,
	title = {Posterior Scleral Cyst in a Pediatric Patient},
	journal = {Ophthalmology},
	volume = {129},
	number = {5},
	year = {2022},
	month = {2022 05},
	pages = {529},
	keywords = {Child, Cysts, Humans, Sclera, Scleral Diseases},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.11.008},
	author = {Hoyek, Sandra and Aronow, Mary Elizabeth and Patel, Nimesh A}
}
@article {1354347,
	title = {Ex-vivo tolerogenic F4/80$^{+}$ antigen-presenting cells (APC) induce efferent CD8$^{+}$ regulatory T cell-dependent suppression of experimental autoimmune uveitis},
	journal = {Clin Exp Immunol},
	volume = {176},
	number = {1},
	year = {2014},
	month = {2014 Apr},
	pages = {37-48},
	abstract = {It is known that inoculation of antigen into the anterior chamber (a.c.) of a mouse eye induces a.c.-associated immune deviation (ACAID), which is mediated in part by antigen-specific local and peripheral tolerance to the inciting antigen. ACAID can also be induced in vivo by intravenous (i.v.) inoculation of ex-vivo-generated tolerogenic antigen-presenting cells (TolAPC). The purpose of this study was to test if in-vitro-generated retinal antigen-pulsed TolAPC suppressed established experimental autoimmune uveitis (EAU). Retinal antigen-pulsed TolAPC were injected i.v. into mice 7 days post-induction of EAU. We observed that retinal antigen-pulsed TolAPC suppressed the incidence and severity of the clinical expression of EAU and reduced the expression of associated inflammatory cytokines. Moreover, extract of whole retina efficiently replaced interphotoreceptor retinoid-binding protein (IRBP) in the preparation of TolAPC used to induce tolerance in EAU mice. Finally, the suppression of EAU could be transferred to a new set of EAU mice with CD8$^{+}$ but not with CD4$^{+}$ regulatory T cells (T(reg)). Retinal antigen-pulsed TolAPC suppressed ongoing EAU by inducing CD8$^{+}$ T(reg) cells that, in turn, suppressed the effector activity of the IRBP-specific T cells and altered the clinical symptoms of autoimmune inflammation in the eye. The ability to use retinal extract for the antigen raises the possibility that retinal extract could be used to produce autologous TolAPC and then used as therapy in human uveitis.},
	keywords = {Animals, Antigen-Presenting Cells, Antigens, Antigens, Differentiation, Autoimmune Diseases, CD8 Antigens, Cells, Cultured, Coculture Techniques, Eye Proteins, Female, Flow Cytometry, Humans, Immune Tolerance, Interferon-gamma, Interleukin-17, Mice, Mice, Inbred C57BL, Retina, Retinol-Binding Proteins, Spleen, T-Lymphocytes, Regulatory, Uveitis},
	issn = {1365-2249},
	doi = {10.1111/cei.12243},
	author = {Hsu, S-M and Mathew, R and Taylor, A W and Stein-Streilein, J}
}
@article {1677791,
	title = {Subretinal gene therapy delays vision loss in a Bardet-Biedl Syndrome type 10 mouse model},
	journal = {Mol Ther Nucleic Acids},
	volume = {31},
	year = {2023},
	month = {2023 Mar 14},
	pages = {164-181},
	abstract = {Blindness in Bardet-Biedl syndrome (BBS) is caused by dysfunction and loss of photoreceptor cells in the retina. BBS10, mutations of which account for approximately 21\% of all BBS cases, encodes a chaperonin protein indispensable for the assembly of the BBSome, a cargo adaptor important for ciliary trafficking. The loss of BBSome function in the eye causes a reduced light sensitivity of photoreceptor cells, photoreceptor ciliary malformation, dysfunctional ciliary trafficking, and photoreceptor cell death. Cone photoreceptors lacking BBS10 have congenitally low electrical function in electroretinography. In this study, we performed gene augmentation therapy by injecting a viral construct subretinally to deliver the coding sequence of the mouse Bbs10 gene to treat retinal degeneration in a BBS10 mouse model. Long-term efficacy was assessed by measuring the electrical functions of the retina over time, imaging of the treated regions to visualize cell survival, conducting visually guided swim assays to measure functional vision, and performing retinal histology. We show that subretinal gene therapy slowed photoreceptor cell death and preserved retinal function in treated eyes. Notably, cone photoreceptors regained their electrical function after gene augmentation. Measurement of functional vision showed that subretinal gene therapy provided a significant benefit in delaying vision loss.},
	issn = {2162-2531},
	doi = {10.1016/j.omtn.2022.12.007},
	author = {Hsu, Ying and Bhattarai, Sajag and Thompson, Jacob M and Mahoney, Angela and Thomas, Jacintha and Mayer, Sara K and Datta, Poppy and Garrison, Janelle and Searby, Charles C and Vandenberghe, Luk H and Seo, Seongjin and Sheffield, Val C and Drack, Arlene V}
}
@article {726221,
	title = {Longitudinal trends in use of targeted therapies for treatment of malignant neoplasms of the eye: a population-based study in Taiwan.},
	journal = {BMJ Open},
	volume = {6},
	number = {5},
	year = {2016},
	month = {2016},
	pages = {e010706},
	abstract = {OBJECTIVES: This study examined the recent trend in use and costs of antineoplastic agents for treatment of eye malignancies in Taiwan from 2009 to 2012. We also forecasted use and costs of targeted therapies up to and including year 2016 based on the current patterns. DESIGN: Retrospective observational study focusing on the usage of targeted therapies for treatment of eye malignancy. SETTING: The monthly claims data for eye malignancy-related antineoplastic agents were retrieved from Taiwan{\textquoteright}s National Health Insurance Research Database (2009-2012). MAIN OUTCOME MEASURES: We calculated the number of prescriptions and costs for each class of medications, and analysed their time trends. In addition, using a time series design with ARIMA models, we estimated the market share by prescription volume and the proportion of costs for targeted therapies for year 2016. RESULTS: The market share by prescription volume of targeted therapies grew from 1.56\% in 2009 to 9.98\% in 2012 among all antineoplastic agents, and the proportion of costs for targeted therapies rose from 15.12\% in 2009 to 58.88\% in 2012. Especially, the proportion of costs for protein kinase inhibitors grew from 25.62\% to 45.28\% among all antineoplastic agents between 2010 and 2012. The market share by prescription volume and the proportion of costs for targeted therapies for treatment of eye malignancies were predicted to reach 27.33\% and 91.39\% by the fourth quarter in 2016, respectively. CONCLUSIONS: This is the first study that examined and forecasted use and costs of targeted therapies for treatment of eye malignancies in Taiwan. Our findings indicate that, compared with other classes of drugs, targeted therapies are having a more and more relevant share among all treatment strategies for eye malignancies in Taiwan, and due to their high costs they are likely to cause great economic burden.},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2015-010706},
	author = {Hsu, Jason C and Gonzalez-Gonzalez, Luis A and Lu, Vicky H and Lu, Christine Y}
}
@article {541291,
	title = {A Dual Role for Corneal Dendritic Cells in Herpes Simplex Keratitis: Local Suppression of Corneal Damage and Promotion of Systemic Viral Dissemination.},
	journal = {PLoS One},
	volume = {10},
	number = {9},
	year = {2015},
	month = {2015},
	pages = {e0137123},
	abstract = {The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV)-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs) and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0137123},
	author = {Hu, Kai and Harris, Deshea L and Yamaguchi, Takefumi and von Andrian, Ulrich H and Hamrah, Pedram}
}
@article {1658687,
	title = {Viability of mitochondria-labeled retinal ganglion cells in organotypic retinal explant cultures by two methods},
	journal = {Exp Eye Res},
	volume = {226},
	year = {2023},
	month = {2023 Jan},
	pages = {109311},
	abstract = {Retinal explant cultures provide a valuable system to study retinal function in vitro. This study established a new retinal explant culture method to prolong the survival of retinal ganglion cells (RGCs). Explants were prepared in two different ways: with or without optic nerve. Retinas from newborn mice that had received an injection of MitoTracker Red into the contralateral superior colliculus to label axonal mitochondria were cultured as organotypic culture for 7 days in vitro. At several time points during the culture, viability of RGCs was assessed by multi-electrode array recording, and morphology by immunohistochemical methods. During the culture, the thickness of the retinal tissue in both groups gradually decreased, however, the structure of the layers of the retina could be identified. Massive apoptosis in the retinal ganglion cell layer (GCL) appeared on the first day of culture, thereafter the number of apoptotic cells decreased. Glial activation was observed throughout the culture, and there was no difference in morphology between the two groups. RGCs loss was exacerbated on 3rdday of culture, and RGCs loss in retinal explants with preserved optic nerve was significantly lower than in retinas that did not preserve the optic nerve. More and longer-lasting mitochondrial signals were observed in the injured area of the optic nerve-preserving explants. Retinal explants provide an invaluable tool for studying retinal function and developing treatments for ocular diseases. The optic nerve-preserving culture helps preserve the integrity of RGCs. The higher number of mitochondria in the nerve-preserving cultures may help maintain viability of RGCs.},
	keywords = {Animals, Axons, Mice, Mitochondria, Optic Nerve, Optic Nerve Injuries, Retina, Retinal Ganglion Cells},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2022.109311},
	author = {Hu, Baoqi and Huang, Yaoyao and Jakobs, Tatjana C and Kang, Qianyan and Lv, Ziwei and Liu, Wenxuan and Wang, Rui}
}
@article {1651345,
	title = {Children with strabismus and amblyopia presented abnormal spontaneous brain activities measured through fractional amplitude of low-frequency fluctuation (fALFF)},
	journal = {Front Neurol},
	year = {2022},
	author = {Hu, XQ and Shi, YD and Chen, J and You, Z and Pan, YC and Ling, Q and Wei, H and Zou, J and Ying, P and Liao, XL and Su, T and Wang, Y.X. and Shao, Y}
}
@article {1677736,
	title = {Interaction network of extracellular vesicles building universal analysis via eye tears: iNEBULA},
	journal = {Sci Adv},
	volume = {9},
	number = {11},
	year = {2023},
	month = {2023 Mar 17},
	pages = {eadg1137},
	abstract = {Discovering the secrets of diseases from tear extracellular vesicles (EVs) is well-recognized and appreciated. However, a precise understanding of the interaction network between EV populations and their biogenesis from our body requires more in-depth and systematic analysis. Here, we report the biological profiles of different-size tear EV subsets from healthy individuals and the origins of EV proteins. We have identified about 1800 proteins and revealed the preferential differences in the biogenesis among distinct subsets. We observe that eye-related proteins that maintain retinal homeostasis and regulate inflammation are preferentially enriched in medium-size EVs (100 to 200 nm) fractions. Using universal analysis in combination with the Human Protein Atlas consensus dataset, we found the genesis of tear EV proteins with 37 tissues and 79 cell types. The proteins related to retinal neuronal cells, glial cells, and blood and immune cells are selectively enriched among EV subsets. Our studies in heterogeneous tear EVs provide building blocks for future transformative precision molecular diagnostics and therapeutics.},
	keywords = {Extracellular Vesicles, Humans, Inflammation, Proteins},
	issn = {2375-2548},
	doi = {10.1126/sciadv.adg1137},
	author = {Hu, Liang and Liu, Xiaoling and Zheng, Qiaolan and Chen, Wuhe and Hao Xu and Li, Hengrui and Luo, Jiaxin and Yang, Rui and Mao, Xulong and Wang, Siyao and Chen, Tucan and Lee, Luke P and Liu, Fei}
}
@article {313101,
	title = {Cholesterol crystals induce inflammatory cytokines expression in a human retinal pigment epithelium cell line by activating the NF-κB pathway.},
	journal = {Discov Med},
	volume = {18},
	number = {97},
	year = {2014},
	month = {2014 Jul-Aug},
	pages = {7-14},
	abstract = {PURPOSE: To investigate the expression of inflammatory cytokines in ARPE-19 cells after stimulation with cholesterol crystals. METHODS: APRE-19 cells were cultured, primed with IL-1α, and treated with cholesterol crystals under different concentrations. Inflammatory cytokines (mature-IL-1β, IL-6, and IL-8) in supernatant and inflammatory cytokines (pro-IL-1β, IL-18) in cell lysate were detected by western blot. The NF-κB pathway inhibitor BAY 11-7082 was used to determine the pathway of cytokine expression. RESULTS: Cholesterol crystals did not induce the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome, but did increase pro-IL-1β expression in ARPE-19 cells. Cholesterol crystals increased pro-IL-1β expression by activating the NF-κB pathway. Cholesterol crystal activation of the NF-κB pathway also leads to increased IL-6 and IL-8 expression. CONCLUSION: Cholesterol crystals can induce inflammatory cytokine expression in ARPE-19 cells by activating the NF-κB pathway.},
	issn = {1944-7930},
	author = {Hu, Yijun and Lin, Haijiang and Dib, Bernard and Atik, Alp and Bouzika, Peggy and Lin, Christopher and Yan, Yueran and Tang, Shibo and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1417561,
	title = {Advances in capsulorhexis},
	journal = {Curr Opin Ophthalmol},
	volume = {30},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {19-24},
	abstract = {PURPOSE OF REVIEW: Continuous curvilinear manual capsulorhexis is currently the standard of cataract surgery. In the past several years, new technologies have been developed to improve the consistency and safety of capsulorhexis creation. This article reviews the most recent technologies in capsulotomy formation and their advantages and disadvantages. RECENT FINDINGS: Guidance devices, femtosecond laser capsulotomy and precision pulse capsulotomy improve the centration, circularity and precision of anterior capsulorhexis and capsulotomy. These developments show particular promise for complex cataract surgeries, though clinical data on the refractive outcomes and complication rates of these technologies are currently limited and warrant additional investigation. SUMMARY: New technological advances in capsulorhexis help surgeons achieve a more ideal capsulotomy geometry. Whether this translates into more predictable refractive outcomes and safer surgeries remains an area of future study.},
	keywords = {Anterior Capsule of the Lens, Capsulorhexis, Cataract Extraction, Humans, Laser Therapy, Visual Acuity},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000539},
	author = {Hu, Wen Fan and Chen, Sherleen H}
}
@article {1517186,
	title = {Elements of the Endomucin Extracellular Domain Essential for VEGF-Induced VEGFR2 Activity},
	journal = {Cells},
	volume = {9},
	number = {6},
	year = {2020},
	month = {2020 Jun 05},
	abstract = {Endomucin (EMCN) is the type I transmembrane glycoprotein, mucin-like component of the endothelial cell glycocalyx. We have previously shown that EMCN is necessary for vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2) internalization and downstream signaling. To explore the structural components of EMCN that are necessary for its function and the molecular mechanism of EMCN in VEGF-induced endothelial functions, we generated a series of mouse EMCN truncation mutants and examined their ability to rescue VEGF-induced endothelial functions in human primary endothelial cells (EC) in which endogenous EMCN had been knocked down using siRNA. Expression of the mouse full-length EMCN (FL EMCN) and the extracellular domain truncation mutants ∆21-81 EMCN and ∆21-121 EMCN, but not the shortest mutant ∆21-161 EMCN, successfully rescued the VEGF-induced EC migration, tube formation, and proliferation. ∆21-161 EMCN failed to interact with VEGFR2 and did not facilitate VEGFR2 internalization. Deletion of COSMC (C1GalT1C1) revealed that the abundant mucin-type -glycans were not required for its VEGFR2-related functions. Mutation of the two -glycosylation sites on ∆21-121 EMCN abolished its interaction with VEGFR2 and its function in VEGFR2 internalization. These results reveal ∆21-121 EMCN as the minimal extracellular domain sufficient for VEGFR2-mediated endothelial function and demonstrate an important role for -glycosylation in VEGFR2 interaction, internalization, and angiogenic activity.},
	issn = {2073-4409},
	doi = {10.3390/cells9061413},
	author = {Hu, Zhengping and Cano, Issahy and Saez-Torres, Kahira L and LeBlanc, Michelle E and Saint-Geniez, Magali and Ng, Yin-Shan and Arg{\"u}eso, Pablo and D{\textquoteright}Amore, Patricia A}
}
@article {1773441,
	title = {Refractive Status and Biometric Characteristics of Children With Familial Exudative Vitreoretinopathy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {13},
	year = {2023},
	month = {2023 Oct 03},
	pages = {27},
	abstract = {PURPOSE: To compare biometric characteristics between patients with early-stage familial exudative vitreoretinopathy (FEVR) and healthy controls. METHODS: This case-control study included 50 FEVR eyes in stage 1-2 and 50 control eyes matched by age, gender and spherical equivalent (SE). Biometric parameters including axial length (AL), white-to-white diameter (WTW), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), pupil diameter, vitreous chamber depth, anterior and posterior corneal surface curvature radius (ACR and PCR), anterior lens surface curvature radius (ALR) and posterior lens surface curvature radius were measured using IOLMaster 700 and compared between cases and controls using paired t-test. Correlations between SE and biometric measures were assessed using Pearson correlation coefficient (r) in cases and controls. RESULTS: Both FEVR cases and matched controls had a mean age of 7.6 years, 48\% female and mean SE of -5.3\&nbsp;D (80\% myopia). Compared to controls, FEVR eyes had smaller AL (P = 0.009), WTW (P = 0.001), ACD (P \&lt; 0.001), and ALR (P = 0.03), but larger CCT (P = 0.02) and LT (P = 0.01). In FEVR eyes, SE was negatively correlated with AL (r = -0.79, P \&lt; 0.001), positively correlated with ACR (r = 0.29, P = 0.04) and PCR (r = 0.33, P = 0.02), whereas in controls, SE was negatively correlated with AL (r = -0.82, P \&lt; 0.001) and LT (r = -0.34, P = 0.02), positively correlated with ALR (r = 0.29, P = 0.04). CONCLUSIONS: Patients at early stage of FEVR exhibited a unique eye morphology resembling ocular development arrest, which may help to develop screening and early detection tools for FEVR. In FEVR patients, myopia is very prevalent and significantly associated with corneal curvature increase.},
	keywords = {Anterior Chamber, Anterior Eye Segment, Axial Length, Eye, Biometry, Case-Control Studies, Child, Familial Exudative Vitreoretinopathies, Female, Humans, Male, Myopia},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.13.27},
	author = {Hu, Yarou and Fan, Zixin and Zhao, Xinyu and Correa, Victor S M C and Wu, Zhenquan and Lu, Xiaofeng and Zeng, Xianlu and Chen, Laijiao and Yu, Zhen and Zheng, Lei and He, Jicang and Zhang, Guoming}
}
@article {1528407,
	title = {Six-Year Incidence and Causes of Low Vision and Blindness in a Rural Chinese Adult Population: The Handan Eye Study},
	journal = {Ophthalmic Epidemiol},
	volume = {28},
	number = {2},
	year = {2021},
	month = {2021 04},
	pages = {160-168},
	abstract = {PURPOSE: To determine the six-year incidence, risk factors, and causes of visual impairment in a Chinese population. METHODS: This was a population-based study of eye disease in Chinese adults in a rural district of Handan in China. 6,830 individuals were invited to participate in 2006 and 5,394 returned for follow-up in 2012. All participants underwent standardized eye examinations. Visual impairment was defined according to WHO criteria. The incidence of visual impairment was age- and gender-standardized to the 2010 China Census. Multivariable logistic regression analysis was used to determine risk factors for visual impairment. RESULTS: The leading causes of visual impairment were cataract and refractive error. Based on (PVA), the six-year incidence rates of low vision and blindness were 5.2\% and 0.5\%, respectively. Incidence of low vision was associated with older age ( \&lt;\&nbsp;.001), less education ( \&lt;\&nbsp;.001), diabetes ( \&lt;\&nbsp;.05), and lower BMI ( \&lt;\&nbsp;.001). The incidence of blindness was associated with diabetes ( \&lt;\&nbsp;.05). Based on (BCVA), the six-year incidence rates of low vision and blindness were 0.8\% and 0.1\%, respectively. Incidence of low vision was associated with older age ( \&lt;\&nbsp;.001) and lower BMI ( \&lt;\&nbsp;.05). None of these factors were associated with the incidence of blindness. CONCLUSION: In Handan, the incidence of visual impairment was high and associated with older age, less education, diabetes, and lower BMI. The majority of cases were due to unoperated cataract and uncorrected refractive error, reflecting the need for improved eye care in this region.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2020.1795886},
	author = {Hu, Ailian and Gu, Sophie Z and Friedman, David S and Cao, Kai and Wang, Ningli}
}
@article {1549002,
	title = {Regulation of Connexin Gap Junctions and Hemichannels by Calcium and Calcium Binding Protein Calmodulin},
	journal = {Int J Mol Sci},
	volume = {21},
	number = {21},
	year = {2020},
	month = {2020 Nov 02},
	abstract = {Connexins are the structural components of gap junctions and hemichannels that mediate the communication and exchange of small molecules between cells, and between the intracellular and extracellular environment, respectively. Connexin (Cx) 46 is predominately expressed in lens fiber cells, where they function in maintaining the homeostasis and transparency of the lens. Cx46 mutations are associated with impairment of channel function, which results in the development of congenital cataracts. Cx46 gap junctions and hemichannels are closely regulated by multiple mechanisms. Key regulators of Cx46 channel function include Ca and calmodulin (CaM). Ca plays an essential role in lens homeostasis, and its dysregulation causes cataracts. Ca associated CaM is a well-established inhibitor of gap junction coupling. Recent studies suggest that elevated intracellular Ca activates Cx hemichannels in lens fiber cells and Cx46 directly interacts with CaM. A Cx46 site mutation (Cx46-G143R), which is associated with congenital Coppock cataracts, shows an increased Cx46-CaM interaction and this interaction is insensitive to Ca, given that depletion of Ca reduces the interaction between CaM and wild-type Cx46. Moreover, inhibition of CaM function greatly reduces the hemichannel activity in the Cx46 G143R mutant. These research findings suggest a new regulatory mechanism by which enhanced association of Cx46 with CaM leads to the increase in hemichannel activity and dysregulation may lead to cataract development. In this review, we will first discuss the involvement of Ca/CaM in lens homeostasis and pathology, and follow by providing a general overview of Ca/CaM in the regulation of Cx46 gap junctions. We discuss the most recent studies concerning the molecular mechanism of Ca/CaM in regulating Cx46 hemichannels. Finally, we will offer perspectives of the impacts of Ca/CaM and dysregulation on Cx46 channels and vice versa.},
	issn = {1422-0067},
	doi = {10.3390/ijms21218194},
	author = {Hu, Zhengping and Riquelme, Manuel A and Gu, Sumin and Jiang, Jean X}
}
@article {1580471,
	title = {Surgical correction of recurrent epiblepharon in Chinese children using modified skin re-draping epicanthoplasty},
	journal = {Int J Ophthalmol},
	volume = {14},
	number = {2},
	year = {2021},
	month = {2021},
	pages = {217-222},
	abstract = {AIM: To evaluate the clinical efficacy of the modified skin re-draping epicanthoplasty procedure for correction of recurrent lower lid epiblepharon in Chinese children. METHODS: From 2016 to 2018, 18 children (10 males and 8 females, average age 6.2{\textpm}1.7y; 30 eyes) with recurrent epiblepharon who attended Beijing Children{\textquoteright}s Hospital were included in the study. All the children had undergone lower eyelid surgery for epiblepharon. Surgical design included using an additional incision along the upper palpebral margin, to avoid vertical scarring on the upper lid. The re-draping method was used to correct recurrent epiblepharon. Follow-up ranged from 3 to 24mo. Postoperative surgical outcomes, complications, and subjective satisfaction were evaluated. RESULTS: Complete correction of cilia touching the cornea was observed in all patients during an average follow-up of 7.1mo. No "dog ears" or obvious scars were formed after surgery. All parents were satisfied with the cosmetic results and none complained. Mean astigmatism decreased from 2.39{\textpm}0.79 diopter (D) preoperatively to 2.19{\textpm}0.79 D at 6mo after surgery; however, the difference was not significant. Best-corrected visual acuity improved, although the change in mean visual acuity was not significant. No recurrence occurred during the follow-up period. CONCLUSION: This surgical modified skin re-draping technique is effective and highly satisfactory for correction of recurrent epiblepharon. The approach is characterized by a simple design, a straightforward procedure, inconspicuous scarring, and good postoperative appearance.},
	issn = {2222-3959},
	doi = {10.18240/ijo.2021.02.06},
	author = {Hu, Shou-Long and Shi, Wen-Qing and Su, Ting and Ge, Qian-Min and Li, Qiu-Yu and Li, Biao and Liang, Rong-Bin and Zhu, Pei-Wen and Shao, Yi}
}
@article {1573105,
	title = {Progressive retinal vessel malformation in a premature infant with Sturge-Weber syndrome: a case report and a literature review of ocular manifestations in Sturge-Weber syndrome},
	journal = {BMC Ophthalmol},
	volume = {21},
	number = {1},
	year = {2021},
	month = {2021 Jan 22},
	pages = {56},
	abstract = {BACKGROUND: Sturge-Weber syndrome is a disorder marked by a distinctive facial capillary malformation, neurological abnormalities, and ocular abnormalities such as glaucoma and choroidal hemangioma. CASE PRESENTATION: We report a case of progressively formed retinal vessel malformation in a premature male infant with Sturge-Weber syndrome and retinopathy of prematurity, after treatment with intravitreal anti-vascular endothelial growth factor (VEGF). The baby was born at 30 weeks gestation with a nevus flammeus involving his left eyelids and maxillary area. On postmenstrual age week 39, he received intravitreal anti-VEGF. Diffuse choroidal hemangioma became evident at 40 weeks, with the classic "tomato catsup fundus" appearance. These clinical findings characterized Sturge-weber syndrome. He presented with posterior retinal vessel tortuosity and vein-to-vein anastomoses at 44 weeks. CONCLUSION: This is a rare case of documented progression of retinal vessel malformations in a patient with Sturge-Weber syndrome and retinopathy of prematurity.},
	issn = {1471-2415},
	doi = {10.1186/s12886-021-01815-8},
	author = {Hu, Zhengping and Cao, Jian and Choi, Eun Young and Li, Yun}
}
@article {1318862,
	title = {Pathological conversion of regulatory T cells is associated with loss of allotolerance},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 May 04},
	pages = {7059},
	abstract = {CD4CD25Foxp3 Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing, we investigated the phenotypic plasticity of Foxp3 Tregs in a well-characterized murine model of corneal transplantation. In order to subvert the normal immune privilege of the cornea and foster an inflammatory milieu, host mice were exposed to desiccating stress prior to transplantation. Treg frequencies and function were decreased following desiccating stress, and this corresponded to decreased graft survival. A fraction of Tregs converted to IL-17 or IFNγ {\textquoteright}exFoxp3{\textquoteright} T cells that were phenotypically indistinguishable from effector Th17 or Th1 cells, respectively. We investigated how Foxp3 expression is modulated in different Treg subsets, demonstrating that neuropilin-1 peripherally-derived Tregs are particularly susceptible to conversion to IL-17/IFNγ exFoxp3 cells in response to cues from their microenvironment. Finally, we show that IL-6 and IL-23 are implicated in the conversion of Tregs to exFoxp3 cells. This report demonstrates that the pathological conversion of Tregs contributes to the loss of corneal immune privilege.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-25384-x},
	author = {Hua, Jing and Inomata, Takenori and Chen, Yihe and Foulsham, William and Stevenson, William and Shiang, Tina and Bluestone, Jeffrey A and Dana, Reza}
}
@article {1661596,
	title = {Association of Placental Growth Factor and Angiopoietin in Human Retinal Endothelial Cell-Pericyte co-Cultures and iPSC-Derived Vascular Organoids},
	journal = {Curr Eye Res},
	volume = {48},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {297-311},
	abstract = {PURPOSE: Placental growth factor (PlGF) and Angiopoietin (Ang)-1 are two proteins that are involved in the regulation of endothelial cell (EC) growth and vasculature formation. In the retina and endothelial cells, pericytes are the major source of both molecules. The purpose of this study is to examine the association of PlGF and Ang-1 with human EC/pericyte co-cultures and iPSC-derived vascular organoids. METHODS: In this study, we used co-cultures of human primary retinal endothelial cells (HREC) and primary human retinal pericytes (HRP), western blotting, immunofluorescent analysis, TUNEL staining, LDH-assays, and RNA seq analysis, as well as human-induced pluripotent stem cells (iPSC), derived organoids (VO) to study the association between PlGF and Ang-1. RESULTS: Inhibition of PlGF by PlGF neutralizing antibody in HREC-HRP co-cultures resulted in the increased expression of Ang-1 and Tie-2 in a dose-dependent manner. This upregulation was not observed in HREC and HRP monocultures but only in co-cultures suggesting the association of pericytes and endothelial cells. Furthermore, Vascular endothelial growth factor receptor 1 (VEGFR1) inhibition abolished the Ang-1 and Tie-2 upregulation by PlGF inhibition. The pericyte viability in high-glucose conditions was also reduced by VEGFR1 neutralization. Immunofluorescent analysis showed that Ang-1 and Ang-2 were expressed mainly by perivascular cells in the VO. RNA seq analysis of the RNA isolated from VO in high glucose conditions indicated increased PlGF and Ang-2 expressions in the VO. PlGF inhibition increased the expression of Ang-1 and Tie-2 in VO, increasing the pericyte coverage of the VO microvascular network. CONCLUSION: Combined, these results suggest PlGF{\textquoteright}s role in the regulation of Ang-1 and Tie-2 expression through VEGFR1. These findings provide new insights into the neovascularization process in diabetic retinopathy and new targets for potential therapeutic intervention.},
	keywords = {Angiopoietins, Coculture Techniques, Endothelial Cells, Female, Glucose, Humans, Induced Pluripotent Stem Cells, Pericytes, Placenta Growth Factor, Retina, Vascular Endothelial Growth Factor A},
	issn = {1460-2202},
	doi = {10.1080/02713683.2022.2149808},
	author = {Huang, Hu and Saddala, Madhu Sudhana and Mukwaya, Anthony and Mohan, Rajiv R and Lennikov, Anton}
}
@article {1417562,
	title = {Habitual consumption of long-chain n-3 PUFAs and fish attenuates genetically associated long-term weight gain},
	journal = {Am J Clin Nutr},
	volume = {109},
	number = {3},
	year = {2019},
	month = {2019 Mar 01},
	pages = {665-673},
	abstract = {BACKGROUND: A growing amount of data suggests that n-3 (ω-3) polyunsaturated fatty acid (PUFA) intake may modify the genetic association with weight change. OBJECTIVES: We aimed to prospectively test interactions of habitual consumption of n-3 PUFAs or fish, the major food source, with overall genetic susceptibility on long-term weight change. DESIGN: Gene-diet interactions were examined in 11,330 women from the Nurses{\textquoteright} Health Study (NHS), 6773 men from the Health Professionals Follow-Up Study (HPFS), and 6254 women from the Women{\textquoteright}s Health Initiative (WHI). RESULTS: In the NHS and HPFS cohorts, food-sourced long-chain n-3 PUFA intake showed directionally consistent interactions with genetic risk score on long-term changes in BMI (P-interaction\&nbsp;=\&nbsp;0.01 in the HPFS, 0.15 in the NHS, and 0.01 in both cohorts combined). Such interactions were successfully replicated in the WHI, an independent cohort (P-interaction\&nbsp;=\&nbsp;0.02 in the WHI and 0.01 in the combined 3 cohorts). The genetic associations with changes in BMI (in kg/m2) consistently decreased (0.15, 0.10, 0.07, and -0.14 per 10 BMI-increasing alleles) across the quartiles of long-chain n-3 PUFAs in the combined cohorts. In addition, high fish intake also attenuated the genetic associations with long-term changes in BMI in the HPFS (P-interaction\&nbsp;=\&nbsp;0.01), NHS (P-interaction\&nbsp;=\&nbsp;0.03), WHI (P-interaction\&nbsp;=\&nbsp;0.10), and the combined cohorts (P-interaction\&nbsp;=\&nbsp;0.01); and the differences in BMI changes per 10 BMI-increasing alleles were 0.16, 0.06, -0.08, and -0.18, respectively, across the categories (<=1, 1\~{}4, 4\~{}6, and >=7 servings/wk) of total fish intake. Similar interactions on body weight were observed for fish intake (P-interaction\&nbsp;=\&nbsp;0.003) and long-chain n-3 PUFA intake (P-interaction\&nbsp;=\&nbsp;0.12). CONCLUSION: Our study provides replicable evidence to show that high intakes of fish and long-chain n-3 PUFAs are associated with an attenuation of the genetic association with long-term weight gain based on results from 3 prospective cohorts of Caucasians.},
	issn = {1938-3207},
	doi = {10.1093/ajcn/nqy238},
	author = {Huang, Tao and Wang, Tiange and Heianza, Yoriko and Zheng, Yan and Sun, Dianjianyi and Kang, Jae H and Pasquale, Louis R and Rimm, Eric B and Manson, JoAnn E and Hu, Frank B and Qi, Lu}
}
@article {1638577,
	title = {PRAME Expression in Junctional Melanocytic Proliferations of the Conjunctiva: A Potential Biomarker for Primary Acquired Melanosis/Conjunctival Melanocytic Intraepithelial Lesions},
	journal = {Am J Dermatopathol},
	volume = {44},
	number = {10},
	year = {2022},
	month = {2022 Oct 01},
	pages = {734-740},
	abstract = {ABSTRACT: Conjunctival melanocytic proliferations are diagnostically challenging, often complicated by small specimen size, and are separated into 3 broad categories. The first group includes benign nevi and primary acquired melanosis (PAM) without atypia. The second group includes junctional melanocytic proliferations with a risk of progression to invasive melanoma (PAM with atypia). The last category is conjunctival melanoma, of which 65\% of tumors arise in the setting of PAM with atypia. Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has been widely adopted to differentiate cutaneous nevi and melanoma. However, there are limited studies on its utility in the evaluation of conjunctival melanocytic proliferations with little data regarding its potential utility in stratifying PAM. Twenty-eight clinically annotated cases (14 PAM without atypia and 14 PAM with atypia) were retrospectively evaluated with PRAME/MART-1 duplex immunohistochemistry and were assigned the commonly used PRAME immunoreactivity score: 0 for no staining, 1+ for 1\%-25\% of cells positive, 2+ for 26\%-50\%, 3+ for 51\%-75\%, and 4+ for \&gt;75\%. PAM without atypia showed low (0-3+) PRAME expression in 14 of 14 cases (100\%). PAM with atypia showed strong and diffuse (4+) PRAME expression in 12 of 14 cases (86.7\%). Seven of eight (87.5\%) PAM with severe atypia, 4 of 4 PAM (100\%) with moderate atypia, and 1 of 2 PAM (50\%) with mild atypia showed 4+ PRAME expression. In addition, all 5 cases that recurred or progressed (all classified as PAM with atypia) showed 4+ PRAME expression. Although additional larger studies are needed, PRAME seems to be a useful adjunct in evaluating junctional melanocytic proliferations of the conjunctiva.},
	keywords = {Antigens, Neoplasm, Biomarkers, Conjunctiva, Conjunctival Neoplasms, Humans, Melanoma, Melanosis, Neoplasm Recurrence, Local, Nevus, Retrospective Studies, Skin Neoplasms},
	issn = {1533-0311},
	doi = {10.1097/DAD.0000000000002201},
	author = {Huang, Yuan Y and Hrycaj, Steven M and Chan, May P and Stagner, Anna M and Patel, Rajiv M and Bresler, Scott C}
}
@article {1655702,
	title = {Retinal microvasculature alteration in patients with systemic sclerosis and chloroquine treatment},
	journal = {Quant Imaging Med Surg},
	volume = {12},
	number = {10},
	year = {2022},
	month = {2022 Oct},
	pages = {4885-4899},
	abstract = {Background: Retinal vascular abnormality is an important part of ocular systemic sclerosis (SSc), and long-term use of chloroquine can lead to retinal toxicity. This study was conducted to evaluate retinal microvascular changes using optical coherence tomography angiography (OCTA) in patients with SSc and SSc patients on long-term chloroquine treatment. Methods: Fifteen SSc patients without chloroquine (30 eyes), 15 SSc patients taking long-term chloroquine (30 eyes) and 15 healthy controls (30 eyes) were recruited to this cross-sectional study. OCTA was used to examine the superficial and deep retinal capillary plexus in the macular retina of each eye. The densities of microvessels (MIR), macrovessels (MAR) and total microvessels (TMI) in the superficial and deep retina of the three groups were calculated and compared. We used the hemisphere segmentation method [superior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)] and Early Treatment Diabetic Retinopathy Study (ETDRS) method [right (R), superior (S), left (L), and inferior (I)] to analyze changes in retinal microvascular density. Results: The superficial and deep retinal MIR density in SSc patients decreased (P\&lt;0.05) compared with the healthy control group. This significant difference was found in both superficial and deep layers in S, L, SR, SL and IL regions (P\&lt;0.05), and additionally in the R and I regions in the superficial layer (P\&lt;0.05). Similarly, compared with SSc patients who did not take chloroquine, the superficial and deep retinal MIR density of SSc patients on long-term chloroquine also decreased (P\&lt;0.05). This significant difference was found in both superficial and deep layers in R, I and IL regions (P\&lt;0.05), and additionally in the IR region in the superficial layer (P\&lt;0.05). Conclusions: The OCTA results suggest that retinal MIR density is decreased in SSc patients, and that long-term use of chloroquine will aggravate this damage, resulting in a further decrease in retinal MIR density.},
	issn = {2223-4292},
	doi = {10.21037/qims-21-1166},
	author = {Huang, Tao and Liang, Rong-Bin and Zhang, Li-Juan and Shu, Hui-Ye and Ge, Qian-Min and Liao, Xu-Lin and Wu, Jie-Li and Su, Ting and Pan, Yi-Cong and Zhou, Qiong and Shao, Yi}
}
@article {1323927,
	title = {Anatomical and functional dichotomy of ocular itch and pain},
	journal = {Nat Med},
	year = {2018},
	month = {2018 Jul 09},
	abstract = {Itch and pain are refractory symptoms of many ocular conditions. Ocular itch is generated mainly in the conjunctiva and is absent from the cornea. In contrast, most ocular pain arises from the cornea. However, the underlying mechanisms remain unknown. Using genetic axonal tracing approaches, we discover distinct sensory innervation patterns between the conjunctiva and cornea. Further genetic and functional analyses in rodent models show that a subset of conjunctival-selective sensory fibers marked by MrgprA3 expression, rather than corneal sensory fibers, mediates ocular itch. Importantly, the actions of both histamine and nonhistamine pruritogens converge onto this unique subset of conjunctiva sensory fibers and enable them to play a key role in mediating itch associated with allergic conjunctivitis. This is distinct from skin itch, in which discrete populations of sensory neurons cooperate to carry itch. Finally, we provide proof of concept that selective silencing of conjunctiva itch-sensing fibers by pruritogen-mediated entry of sodium channel blocker QX-314 is a feasible therapeutic strategy to treat ocular itch in mice. Itch-sensing fibers also innervate the human conjunctiva and allow pharmacological silencing using QX-314. Our results cast new light on the neural mechanisms of ocular itch and open a new avenue for developing therapeutic strategies.},
	issn = {1546-170X},
	doi = {10.1038/s41591-018-0083-x},
	author = {Huang, Cheng-Chiu and Yang, Weishan and Guo, Changxiong and Jiang, Haowu and Li, Fengxian and Xiao, Maolei and Davidson, Steve and Yu, Guang and Duan, Bo and Huang, Tianwen and Huang, Andrew J W and Liu, Qin}
}
@article {1798436,
	title = {Epidermal Growth Factor Receptor Inhibitors for Lung Cancer and the Risk of Keratitis},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {2},
	year = {2024},
	month = {2024 Feb 01},
	pages = {140-145},
	abstract = {IMPORTANCE: Epidermal growth factor receptor inhibitors (EGFRis) have been reported to be associated with cutaneous and ocular side effects; however, there is limited evidence of an association between EGFRi treatment and keratitis. OBJECTIVE: To determine the association between EGFRi treatment and agents and the risk of new-onset keratitis among patients with lung cancer. DESIGN, SETTING, AND PARTICIPANTS: This US population-based cohort study examined TriNetX data of patients with lung cancer treated with or without EGFRis between May 1, 2003, and October 30, 2023. EXPOSURES: Treatment with EGFRis, including the first-generation agents gefitinib and erlotinib, the second-generation agent afatinib, and the third-generation agent osimertinib. MAIN OUTCOMES AND MEASURES: The risk of new-onset keratitis among patients with lung cancer receiving EGFRi treatment was determined using logistic and Cox proportional hazards regression. RESULTS: Among 1 388 108 patients with lung cancer, 22 225 received EGFRis (mean [SD] age, 69.7 [10.6] years; 62.8\% females and 37.2\% males). Patients treated with EGFRis had a higher risk of keratitis than nonexposed patients (hazard ratio [HR], 1.520; 95\% CI, 1.339-1.725). Subtypes of EGFRi-associated keratitis included keratoconjunctivitis (HR, 1.367; 95\% CI, 1.158-1.615), superficial keratitis (HR, 1.635; 95\% CI, 1.306-2.047), and corneal ulcer (HR, 2.132; 95\% CI, 1.515-3.002). Patients taking afatinib had a higher risk of keratitis (HR, 2.229; 95\% CI, 1.480-3.356). CONCLUSIONS AND RELEVANCE: These findings suggest that patients with lung cancer treated with EGFRis may have an increased risk of new-onset keratitis, especially with the second-generation EGFRi afatinib, supporting the need for prompt diagnosis and management of EGFRi-associated ocular issues to prevent serious complications or treatment disruptions.},
	keywords = {Afatinib, Aged, Cohort Studies, ErbB Receptors, Female, Humans, Keratitis, Lung Neoplasms, Male, Mutation, Protein Kinase Inhibitors},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.6089},
	author = {Huang, Pin-Chia and Lin, Ching-Chieh and Dana, Reza and Ma, Kevin Sheng-Kai}
}
@article {1125316,
	title = {Genome editing abrogates angiogenesis in vivo},
	journal = {Nat Commun},
	volume = {8},
	number = {1},
	year = {2017},
	month = {2017 Jul 24},
	pages = {112},
	abstract = {Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2 plays an essential role, is associated with a variety of human diseases including proliferative diabetic retinopathy and wet age-related macular degeneration. Here we report that a system of adeno-associated virus (AAV)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular endothelial cells (ECs), whereby the expression of SpCas9 is driven by an endothelial-specific promoter of intercellular adhesion molecule 2. We further show that recombinant AAV serotype 1 (rAAV1) transduces ECs of pathologic vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization. This work establishes a strong foundation for genome editing as a strategy to treat angiogenesis-associated diseases.Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.},
	issn = {2041-1723},
	doi = {10.1038/s41467-017-00140-3},
	author = {Huang, Xionggao and Zhou, Guohong and Wu, Wenyi and Duan, Yajian and Ma, Gaoen and Song, Jingyuan and Xiao, Ru and Vandenberghe, Luk and Zhang, Feng and D{\textquoteright}Amore, Patricia A and Lei, Hetian}
}
@article {439646,
	title = {DNA Methylation Variants at HIF3A Locus, B-Vitamin Intake, and Long-term Weight Change: Gene-Diet Interactions in Two U.S. Cohorts.},
	journal = {Diabetes},
	volume = {64},
	number = {9},
	year = {2015},
	month = {2015 Sep},
	pages = {3146-54},
	abstract = {The first epigenome-wide association study of BMI identified DNA methylation at an HIF3A locus associated with BMI. We tested the hypothesis that DNA methylation variants are associated with BMI according to intake of B vitamins. In two large cohorts, we found significant interactions between the DNA methylation-associated HIF3A single nucleotide polymorphism (SNP) rs3826795 and intake of B vitamins on 10-year changes in BMI. The association between rs3826795 and BMI changes consistently increased across the tertiles of total vitamin B2 and B12 intake (all P for interaction \&lt;0.01). The differences in the BMI changes per increment of minor allele were -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B2 intake and -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.10 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B12 intake. In two independent cohorts, a DNA methylation variant in HIF3A was associated with BMI changes through interactions with total or supplemental vitamin B2, vitamin B12, and folate. These findings suggest a potential causal relation between DNA methylation and adiposity.},
	issn = {1939-327X},
	doi = {10.2337/db15-0264},
	author = {Huang, Tao and Zheng, Yan and Qi, Qibin and Xu, Min and Ley, Sylvia H and Li, Yanping and Kang, Jae H and Wiggs, Janey and Pasquale, Louis R and Chan, Andrew T and Rimm, Eric B and Hunter, David J and Manson, JoAnn E and Willett, Walter C and Hu, Frank B and Qi, Lu}
}
@article {1806511,
	title = {Assessment of a Large Language Model{\textquoteright}s Responses to Questions and Cases About Glaucoma and Retina Management},
	journal = {JAMA Ophthalmol},
	year = {2024},
	month = {2024 Feb 22},
	abstract = {IMPORTANCE: Large language models (LLMs) are revolutionizing medical diagnosis and treatment, offering unprecedented accuracy and ease surpassing conventional search engines. Their integration into medical assistance programs will become pivotal for ophthalmologists as an adjunct for practicing evidence-based medicine. Therefore, the diagnostic and treatment accuracy of LLM-generated responses compared with fellowship-trained ophthalmologists can help assess their accuracy and validate their potential utility in ophthalmic subspecialties. OBJECTIVE: To compare the diagnostic accuracy and comprehensiveness of responses from an LLM chatbot with those of fellowship-trained glaucoma and retina specialists on ophthalmological questions and real patient case management. DESIGN, SETTING, AND PARTICIPANTS: This comparative cross-sectional study recruited 15 participants aged 31 to 67 years, including 12 attending physicians and 3 senior trainees, from eye clinics affiliated with the Department of Ophthalmology at Icahn School of Medicine at Mount Sinai, New York, New York. Glaucoma and retina questions (10 of each type) were randomly selected from the American Academy of Ophthalmology{\textquoteright}s Commonly Asked Questions. Deidentified glaucoma and retinal cases (10 of each type) were randomly selected from ophthalmology patients seen at Icahn School of Medicine at Mount Sinai-affiliated clinics. The LLM used was GPT-4 (version dated May 12, 2023). Data were collected from June to August 2023. MAIN OUTCOMES AND MEASURES: Responses were assessed via a Likert scale for medical accuracy and completeness. Statistical analysis involved the Mann-Whitney U test and the Kruskal-Wallis test, followed by pairwise comparison. RESULTS: The combined question-case mean rank for accuracy was 506.2 for the LLM chatbot and 403.4 for glaucoma specialists (n = 831; Mann-Whitney U = 27976.5; P \&lt; .001), and the mean rank for completeness was 528.3 and 398.7, respectively (n = 828; Mann-Whitney U = 25218.5; P \&lt; .001). The mean rank for accuracy was 235.3 for the LLM chatbot and 216.1 for retina specialists (n = 440; Mann-Whitney U = 15518.0; P = .17), and the mean rank for completeness was 258.3 and 208.7, respectively (n = 439; Mann-Whitney U = 13123.5; P = .005). The Dunn test revealed a significant difference between all pairwise comparisons, except specialist vs trainee in rating chatbot completeness. The overall pairwise comparisons showed that both trainees and specialists rated the chatbot{\textquoteright}s accuracy and completeness more favorably than those of their specialist counterparts, with specialists noting a significant difference in the chatbot{\textquoteright}s accuracy (z = 3.23; P = .007) and completeness (z = 5.86; P \&lt; .001). CONCLUSIONS AND RELEVANCE: This study accentuates the comparative proficiency of LLM chatbots in diagnostic accuracy and completeness compared with fellowship-trained ophthalmologists in various clinical scenarios. The LLM chatbot outperformed glaucoma specialists and matched retina specialists in diagnostic and treatment accuracy, substantiating its role as a promising diagnostic adjunct in ophthalmology.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.6917},
	author = {Huang, Andy S and Hirabayashi, Kyle and Barna, Laura and Parikh, Deep and Pasquale, Louis R}
}
@article {1645468,
	title = {An Objective and Easy-to-Use Glaucoma Functional Severity Staging System Based on Artificial Intelligence},
	journal = {J Glaucoma},
	year = {2022},
	month = {2022 Jun 03},
	abstract = {OBJECTIVE: To develop an objective and easy-to-use glaucoma staging system based on visual fields (VFs). SUBJECTS AND PARTICIPANTS: A total of 13,231 VFs from 8077 subjects were used to develop models and 8024 VFs from 4445 subjects were used to validate models. METHODS: We developed an unsupervised machine learning model to identify clusters with similar VF values. We annotated the clusters based on their respective mean deviation (MD). We computed optimal MD thresholds that discriminate clusters with highest accuracy based on Bayes minimum error principle. We evaluated the accuracy of the staging system and validated findings based on an independent validation dataset. RESULTS: The unsupervised k-means algorithm discovered four clusters with 6784, 4034, 1541, and 872 VFs and average MDs of 0.0▒dB ({\textpm}1.4: Standard Deviation), -4.8▒dB ({\textpm}1.9), -12.2▒dB ({\textpm}2.9), and -23.0▒dB ({\textpm}3.8), respectively. The supervised Bayes minimum error classifier identified optimal MD thresholds of -2.2▒dB, -8.0▒dB, and -17.3▒dB for discriminating normal eyes and eyes at the early, moderate, and advanced stages of glaucoma. The accuracy of the glaucoma staging system was 94\%, based on identified MD thresholds with respect to the initial k-means clusters. CONCLUSIONS: We discovered that four severity levels based on MD thresholds of -2.2▒dB, -8.0▒dB, and -17.3▒dB, provides the optimal number of severity stages based on unsupervised and supervised machine learning. This glaucoma staging system is unbiased, objective, easy-to-use, and consistent, which makes it highly suitable for use in glaucoma research and for day-to-day clinical practice.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002059},
	author = {Huang, Xiaoqin and Saki, Fatemeh and Wang, Mengyu and Tobias Elze and Boland, Michael V and Pasquale, Louis R and Johnson, Chris A and Yousefi, Siamak}
}
@article {1016061,
	title = {Editing VEGFR2 Blocks VEGF-Induced Activation of Akt and Tube Formation},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {2},
	year = {2017},
	month = {2017 Feb 01},
	pages = {1228-1236},
	abstract = {Purpose: Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in VEGF-induced angiogenesis. The goal of this project was to test the hypothesis that editing genomic VEGFR2 loci using the technology of clustered regularly interspaced palindromic repeats (CRISPR)-associated DNA endonuclease (Cas)9 in Streptococcus pyogenes (SpCas9) was able to block VEGF-induced activation of Akt and tube formation. Methods: Four 20 nucleotides for synthesizing single-guide RNAs based on human genomic VEGFR2 exon 3 loci were selected and cloned into a lentiCRISPR v2 vector, respectively. The DNA fragments from the genomic VEGFR2 exon 3 of transduced primary human retinal microvascular endothelial cells (HRECs) were analyzed by Sanger DNA sequencing, surveyor nuclease assay, and next-generation sequencing (NGS). In the transduced cells, expression of VEGFR2 and VEGF-stimulated signaling events (e.g., Akt phosphorylation) were determined by Western blot analyses; VEGF-induced cellular responses (proliferation, migration, and tube formation) were examined. Results: In the VEGFR2-sgRNA/SpCas9-transduced HRECs, Sanger DNA sequencing indicated that there were mutations, and NGS demonstrated that there were 83.57\% insertion and deletions in the genomic VEGFR2 locus; expression of VEGFR2 was depleted in the VEGFR2-sgRNA/SpCas9-transduced HRECs. In addition, there were lower levels of Akt phosphorylation in HRECs with VEGFR2-sgRNA/SpCas9 than those with LacZ-sgRNA/SpCas9, and there was less VEGF-stimulated Akt activation, proliferation, migration, or tube formation in the VEGFR2-depleted HRECs than those treated with aflibercept or ranibizumab. Conclusions: The CRISPR-SpCas9 technology is a potential novel approach to prevention of pathologic angiogenesis.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20537},
	author = {Huang, Xionggao and Zhou, Guohong and Wu, Wenyi and Ma, Gaoen and D{\textquoteright}Amore, Patricia A and Mukai, Shizuo and Lei, Hetian}
}
@article {1608603,
	title = {Estimating the Severity of Visual Field Damage From Retinal Nerve Fiber Layer Thickness Measurements With Artificial Intelligence},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {9},
	year = {2021},
	month = {2021 Aug 02},
	pages = {16},
	abstract = {Purpose: The purpose of this study was to assess the accuracy of artificial neural networks (ANN) in estimating the severity of mean deviation (MD) from peripapillary retinal nerve fiber layer (RNFL) thickness measurements derived from optical coherence tomography (OCT). Methods: Models were trained using 1796 pairs of visual field and OCT measurements from 1796 eyes to estimate visual field MD from RNFL data. Multivariable linear regression, random forest regressor, support vector regressor, and 1D convolutional neural network (CNN) models with sectoral RNFL thickness measurements were examined. Three independent subsets consisting of 698, 256, and 691 pairs of visual field and OCT measurements were used to validate the models. Estimation errors were visualized to assess model performance subjectively. Mean absolute error (MAE), root mean square error (RMSE), median absolute error, Pearson correlation, and R-squared metrics were used to assess model performance objectively. Results: The MAE and RMSE of the ANN model based on the testing dataset were 4.0 dB (95\% confidence interval = 3.8-4.2) and 5.2 dB (95\% confidence interval = 5.1-5.4), respectively. The ranges of MAE and RMSE of the ANN model on independent datasets were 3.3-5.9 dB and 4.4-8.4 dB, respectively. Conclusions: The proposed ANN model estimated MD from RNFL measurements better than multivariable linear regression model, random forest, support vector regressor, and 1-D CNN models. The model was generalizable to independent data from different centers and varying races. Translational Relevance: Successful development of ANN models may assist clinicians in assessing visual function in glaucoma based on objective OCT measures with less dependence on subjective visual field tests.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.9.16},
	author = {Huang, Xiaoqin and Sun, Jian and Majoor, Juleke and Vermeer, Koenraad Arndt and Lemij, Hans and Tobias Elze and Wang, Mengyu and Boland, Michael Vincent and Pasquale, Louis Robert and Mohammadzadeh, Vahid and Nouri-Mahdavi, Kouros and Johnson, Chris and Yousefi, Siamak}
}
@article {1638559,
	title = {Head and Neck Region Dermatological Ultraviolet-Related Cancers are Associated with Exfoliation Syndrome in a Clinic-Based Population},
	journal = {Ophthalmol Glaucoma},
	volume = {5},
	number = {6},
	year = {2022},
	month = {2022 Nov-Dec},
	pages = {663-671},
	abstract = {OBJECTIVE: We assessed the relationship between ultraviolet (UV)-associated dermatological carcinomas (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) and exfoliation syndrome (XFS) or exfoliation glaucoma (XFG). DESIGN: Case-control study. PARTICIPANTS: Between 2019 and 2021, 321 participants and control subjects (XFS or XFG\&nbsp;= 98; primary open-angle glaucoma [POAG]\&nbsp;= 117; controls\&nbsp;= 106; ages 50-90 years) were recruited. METHODS: A cross-sectional survey assessing medical history, maximum known intraocular pressure, cup-to-disc ratio, Humphrey visual field 24-2, the propensity to tan or burn in early life, history of BCC or SCC, and XFS or XFG diagnosis. The multivariable models adjusted for age, sex, medical history, eye color, hair color, and likeliness of tanning versus burning at a young age. MAIN OUTCOME MEASURES: History of diagnosed XFS or XFG. RESULTS: Any history of BCC or SCC in the head and neck region was associated with a 2-fold higher risk of having XFS or XFG versus having POAG or being a control subject (odds ratio [OR], 2.01; 95\% confidence interval [CI], 1.04-3.89) in a multivariable-adjusted analysis. We observed a dose-response association in which the chance of having XFS or XFG increased by 67\% per head and neck BCC or SCC occurrence (OR, 1.67; 95\% CI, 1.09-2.56). When we excluded POAG participants, head and neck BCC or SCC was associated with a 2.8-fold higher risk of XFS or XFG (OR, 2.80; 95\% CI, 1.12-7.02), and each additional occurrence had a 2-fold higher risk of XFS or XFG (OR, 1.97; 95\% CI, 1.09-3.58). The association between head and neck region BCC or SCC and POAG compared with the control subjects was null (OR, 1.42; 95\% CI, 0.58-3.48). With BCC or SCC located anywhere on the body, there was a nonsignificantly higher risk of having XFS or XFG compared with having POAG or being a control subject (OR, 1.65; 95\% CI, 0.88-3.09). CONCLUSIONS: Head and neck region BCCs or SCCs are associated with a higher risk of having XFS or XFG. These findings support prior evidence that head and neck UV exposure may be a risk factor for XFS.},
	keywords = {Aged, Aged, 80 and over, Case-Control Studies, Cross-Sectional Studies, Exfoliation Syndrome, Glaucoma, Open-Angle, Humans, Middle Aged, Neoplasms},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.04.002},
	author = {Huang, Jeff J and Geduldig, Jack E and Jacobs, Erica B and Tai, Tak Yee T and Ahmad, Sumayya and Chadha, Nisha and Buxton, Douglas F and Vinod, Kateki and Wirostko, Barbara M and Kang, Jae H and Wiggs, Janey L and Ritch, Robert and Pasquale, Louis R}
}
@article {1354348,
	title = {Interocular Shift of Visual Attention Enhances Stereopsis and Visual Acuities of Anisometropic Amblyopes beyond the Critical Period of Visual Development: A Novel Approach},
	journal = {J Ophthalmol},
	volume = {2014},
	year = {2014},
	month = {2014},
	pages = {615213},
	abstract = {Aims. Increasing evidence shows that imbalanced suppressive drive prior to binocular combination may be the key factor in amblyopia. We described a novel binocular approach, interocular shift of visual attention (ISVA), for treatment of amblyopia in adult patients. Methods. Visual stimuli were presented anaglyphically on a computer screen. A square target resembling Landolt C had 2 openings, one in red and one in cyan color. Through blue-red goggles, each eye could only see one of the two openings. The patient was required to report the location of the opening presented to the amblyopic eye. It started at an opening size of 800 sec of arc, went up and down in 160 sec of arc step, and stopped when reaching the 5th reversals. Ten patients with anisometropic amblyopia older than age 14 (average age: 26.7) were recruited and received ISVA treatment for 6 weeks, with 2 training sessions per day. Results. Both Titmus stereopsis (z = -2.809, P = 0.005) and Random-dot stereopsis (z = -2.317, P = 0.018) were significantly improved. Average improvement in best corrected visual acuity (BCVA) was 0.74 line (t = 5.842, P \&lt; 0.001). Conclusions. The ISVA treatment may be effective in treating amblyopia and restoring stereoscopic function.},
	issn = {2090-004X},
	doi = {10.1155/2014/615213},
	author = {Huang, Liwen and Sun, Xinghuai and Luo, Gang and Liu, Shuai and Liu, Rui and Mansouri, Behzad and Wong, Vicky Wing Lai and Wen, Wen and Liu, Hong and Wang, Ai-Hou}
}
@article {1589763,
	title = {Small Incision Lenticule Extraction (SMILE): Myths and Realities},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {140-148},
	abstract = {The emergence of SMILE in the last decade has provided an alternative to LASIK for patients considering cornea laser refractive surgery. SMILE offers a novel approach using the femtosecond laser to create an intrastromal lenticule that can be removed through a small three to four millimeter incision.The purpose of this study is to review the recent literature on popular SMILE claims - reduced iatrogenic dry eye, better recovery of corneal sensation, and a biomechanically stronger cornea - summarize the published outcomes, and determine which claims are myths versus realities.SMILE is still in its infancy as a refractive technique in the US after recent USFDA approval for its treatment of myopia astigmatism in October 2018. Future randomized controlled studies are needed to compare its outcomes to LASIK, which has well-documented good visual outcomes, rapid postoperative recovery, and good safety profile.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1887897},
	author = {Huang, Grace and Melki, Samir}
}
@article {1632282,
	title = {REV-ERBα regulates age-related and oxidative stress-induced degeneration in retinal pigment epithelium via NRF2},
	journal = {Redox Biol},
	volume = {51},
	year = {2022},
	month = {2022 05},
	pages = {102261},
	abstract = {Retinal pigment epithelium (RPE) dysfunction and atrophy occur in dry age-related macular degeneration (AMD), often leading to photoreceptor degeneration and vision loss. Accumulated oxidative stress during aging contributes to RPE dysfunction and degeneration. Here we show that the nuclear receptor REV-ERBα, a redox sensitive transcription factor, protects RPE from age-related degeneration and oxidative stress-induced damage. Genetic deficiency of REV-ERBα leads to accumulated oxidative stress, dysfunction and degeneration of RPE, and AMD-like ocular pathologies in aging mice. Loss of REV-ERBα exacerbates chemical-induced RPE damage, and pharmacological activation of REV-ERBα protects RPE from oxidative damage both in vivo and in vitro. REV-ERBα directly regulates transcription of nuclear factor erythroid 2-related factor 2 (NRF2) and its downstream antioxidant enzymes superoxide dismutase 1 (SOD1) and catalase to counter oxidative damage. Moreover, aged mice with RPE specific knockout of REV-ERBα also exhibit accumulated oxidative stress and fundus and RPE pathologies. Together, our results suggest that REV-ERBα is a novel intrinsic protector of the RPE against age-dependent oxidative stress and a new molecular target for developing potential therapies to treat age-related retinal degeneration.},
	keywords = {Animals, Macular Degeneration, Mice, NF-E2-Related Factor 2, Nuclear Receptor Subfamily 1, Group D, Member 1, Oxidative Stress, Retinal Degeneration, Retinal Pigment Epithelium},
	issn = {2213-2317},
	doi = {10.1016/j.redox.2022.102261},
	author = {Huang, Shuo and Liu, Chi-Hsiu and Wang, Zhongxiao and Fu, Zhongjie and Britton, William R and Blomfield, Alexandra K and Kamenecka, Theodore M and Dunaief, Joshua L and Solt, Laura A and Chen, Jing}
}
@article {1354349,
	title = {Functional and morphological analysis of the subretinal injection of human retinal progenitor cells under Cyclosporin A treatment},
	journal = {Mol Vis},
	volume = {20},
	year = {2014},
	month = {2014},
	pages = {1271-80},
	abstract = {PURPOSE: The purpose of this study is to evaluate the functional and morphological changes in subretinal xenografts of human retinal progenitor cells (hRPCs) in B6 mice treated with Cyclosporin A (CsA; 210 mg/l in drinking water). METHODS: The hRPCs from human fetal eyes were isolated and expanded for transplantation. These cells, with green fluorescent protein (GFP) at 11 passages, were transplanted into the subretinal space in B6 mice. A combination of invasive and noninvasive approaches was used to analyze the structural and functional consequences of the subretinal injection of the hRPCs. The process of change was monitored using spectral domain optical coherence tomography (SDOCT), histology, and electroretinography (ERG) at 3 days, 1 week, and 3 weeks after transplantation. Cell counts were used to evaluate the survival rate with a confocal microscope. ERGs were performed to evaluate the physiologic changes, and the structural changes were evaluated using SDOCT and histological examination. RESULTS: The results of the histological examination showed that the hRPCs gained a better survival rate in the mice treated with CsA. The SDOCT showed that the bleb size of the retinal detachment was significantly decreased, and the retinal reattachment was nearly complete by 3 weeks. The ERG response amplitudes in the CsA group were less decreased after the injection, when compared with the control group, in the dark-adapted and light-adapted conditions. However, the cone-mediated function in both groups was less affected by the transplantation after 3 weeks than the rod-mediated function. CONCLUSIONS: Although significant functional and structural recovery was observed after the subretinal injection of the hRPCs, the effectiveness of CsA in xenotransplantation may be a novel and potential approach for increasing retinal progenitor cell survival.},
	keywords = {Animals, Cell Proliferation, Cell Survival, Cyclosporine, Electroretinography, Fetus, Genes, Reporter, Graft Survival, Green Fluorescent Proteins, Humans, Immunosuppressive Agents, Mice, Mice, Inbred C57BL, Primary Cell Culture, Retina, Stem Cell Transplantation, Stem Cells, Tomography, Optical Coherence, Transplantation, Heterologous},
	issn = {1090-0535},
	author = {Huang, Rui and Baranov, Petr and Lai, Kunbei and Zhang, Xinmei and Ge, Jian and Young, Michael J}
}
@article {1504086,
	title = {BEST1-One Gene, Many Diseases},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Apr 02},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.0683},
	author = {Huckfeldt, Rachel and Sobrin, Lucia}
}
@article {1517187,
	title = {Biallelic -associated retinal dystrophies: Expanding the mutational and clinical spectrum},
	journal = {Mol Vis},
	volume = {26},
	year = {2020},
	month = {2020},
	pages = {423-433},
	abstract = {Purpose: To evaluate the phenotypic spectrum of autosomal recessive associated retinal dystrophies and assess genotypic associations. Methods: A retrospective multicenter study was performed of patients with biallelic -associated retinal dystrophies. Data including presenting symptoms and age, visual acuity, kinetic perimetry, full field electroretinogram, fundus examination, multimodal retinal imaging, and genotype were evaluated. Results: Nineteen eligible patients from 17 families were identified and ranged in age from 10 to 56 years at the most recent evaluation. Ten of the 21 unique variants identified were novel, and mutations within exon 2 accounted for nearly half of alleles across the cohort. Patients had clinical diagnoses of retinitis pigmentosa (13), cone-rod dystrophy (3), Leber congenital amaurosis (1), early-onset severe retinal dystrophy (1), and macular dystrophy (1). Macular atrophy was a common feature across the cohort. Symptom onset occurred between 4 and 30 years of age (mean 14.9 years, median 13 years), but there were clusters of onset age that correlated with the effects of mutations at a protein level. Patients with later-onset disease, including retinitis pigmentosa, had at least one missense variant in an exon 2 DCX domain. Conclusions: Biallelic mutations cause a broad spectrum of retinal disease. Exon 2 missense mutations are a significant contributor to disease and can be associated with a considerably later onset of retinitis pigmentosa than that typically associated with biallelic mutations.},
	issn = {1090-0535},
	author = {Huckfeldt, Rachel M and Grigorian, Florin and Place, Emily and Comander, Jason I and Vavvas, Demetrios and Young, Lucy H and Yang, Paul and Shurygina, Maria and Pierce, Eric A and Pennesi, Mark E}
}
@article {931081,
	title = {Management of Cystoid Macular Edema in Retinitis Pigmentosa.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	pages = {43-51},
	abstract = {Retinitis pigmentosa is a genetically heterogeneous disorder with an estimated prevalence of one in 4,000 that is classically characterized by the progressive constriction of peripheral vision and a later deterioration of visual acuity. Central vision can be compromised earlier in disease, however, in the approximately 25\% of patients that have cystoid macular edema. This poorly understood problem can thus significantly impair patient quality of life, particularly as available treatments have limited efficacy. We will review clinical features of retinitis pigmentosa-associated cystoid macular edema, potential causative mechanisms, and finally, evidence supporting currently employed therapies with emphasis upon which management strategies require further evidence-based evaluation.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228404},
	author = {Huckfeldt, Rachel M and Comander, Jason}
}
@article {1430528,
	title = {Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality},
	journal = {Neuron},
	volume = {101},
	number = {5},
	year = {2019},
	month = {2019 Mar 06},
	pages = {839-862},
	abstract = {Gene transfer has long been a compelling yet elusive therapeutic modality. First mainly considered for rare inherited disorders, gene therapy may open treatment opportunities for more challenging and complex diseases such as Alzheimer{\textquoteright}s or Parkinson{\textquoteright}s disease. Today, examples of striking clinical proof of concept, the first gene therapy drugs coming onto the market, and the emergence of powerful new molecular tools have broadened the number of avenues to target neurological disorders but have also highlighted safety concerns and technology gaps. The vector of choice for many nervous system targets currently is the adeno-associated viral (AAV) vector due to its desirable safety profile and strong neuronal tropism. In aggregate, the clinical success, the preclinical potential, and the technological innovation have made therapeutic AAV drug development a reality, particularly for nervous system disorders. Here, we discuss the rationale, opportunities, limitations, and progress in clinical AAV gene therapy.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2019.02.017},
	author = {Hudry, Eloise and Vandenberghe, Luk H}
}
@article {1328888,
	title = {Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65},
	journal = {Mol Ther Methods Clin Dev},
	volume = {10},
	year = {2018},
	month = {2018 Sep 21},
	pages = {197-209},
	abstract = {Adeno-associated viral vectors (AAVs) have demonstrated potential in applications for neurologic disorders, and the discovery that some AAVs can cross the blood-brain barrier (BBB) after intravenous injection has further expanded these opportunities for non-invasive brain delivery. Anc80L65, a novel AAV capsid designed from reconstruction of the viral evolutionary lineage, has previously demonstrated robust transduction capabilities after local delivery in various tissues such as liver, retina, or cochlea, compared with conventional AAVs. Here, we compared the transduction efficacy of Anc80L65 with conventional AAV9 in the CNS after intravenous, intracerebroventricular (i.c.v.), or intraparenchymal injections. Anc80L65 was more potent at targeting the brain and spinal cord after intravenous injection than AAV9, and mostly transduced astrocytes and a wide range of neuronal subpopulations. Although the efficacy of Anc80L65 and AAV9 is similar after direct intraparenchymal injection in the striatum, Anc80L65{\textquoteright}s diffusion throughout the CNS was more extensive than AAV9 after i.c.v. infusion, leading to widespread expression in the cerebellum. These findings demonstrate that Anc80L65 is a highly efficient gene transfer vector for the murine CNS. Systemic injection of Anc80L65 leads to notable expression in the CNS that does not rely on a self-complementary genome. These data warrant further testing in larger animal models.},
	issn = {2329-0501},
	doi = {10.1016/j.omtm.2018.07.006},
	author = {Hudry, Eloise and Andres-Mateos, Eva and Lerner, Eli P and Volak, Adrienn and Cohen, Olivia and Hyman, Bradley T and Maguire, Casey A and Vandenberghe, Luk H}
}
@article {1511473,
	title = {Prolonged intraocular residence and retinal tissue distribution of a fourth-generation compstatin-based C3 inhibitor in non-human primates},
	journal = {Clin Immunol},
	volume = {214},
	year = {2020},
	month = {2020 May},
	pages = {108391},
	abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Genetic studies in susceptible individuals have linked this ocular disease to deregulated complement activity that culminates in increased C3 turnover, retinal inflammation and photoreceptor loss. Therapeutic targeting of C3 has therefore emerged as a promising strategy for broadly intercepting the detrimental proinflammatory consequences of complement activation in the retinal tissue. In this regard, a PEGylated second-generation derivative of the compstatin family of C3-targeted inhibitors is currently in late-stage clinical development as a treatment option for geographic atrophy, an advanced form of AMD which lacks approved therapy. While efficacy has been strongly suggested in phase 2 clinical trials, crucial aspects still remain to be defined with regard to the ocular bioavailability, tissue distribution and residence, and dosing frequency of such inhibitors in AMD patients. Here we report the intraocular distribution and pharmacokinetic profile of the fourth-generation compstatin analog, Cp40-KKK in cynomolgus monkeys following a single intravitreal injection. Using a sensitive surface plasmon resonance (SPR)-based competition assay and ELISA, we have quantified both the amount of inhibitor and the concentration of C3 retained in the vitreous of Cp40-KKK-injected animals. Cp40-KKK displays prolonged intraocular residence, being detected at C3-saturating levels for over 3\&nbsp;months after a single intravitreal injection. Moreover, we have probed the distribution of Cp40-KKK within the ocular tissue by means of immunohistochemistry and highly specific anti-Cp40-KKK antibodies. Both C3 and Cp40-KKK were detected in the retinal tissue of inhibitor-injected animals, with prominent co-localization in the choroid one-month post intravitreal injection. These results attest to the high retinal tissue penetrance and target-driven distribution of Cp40-KKK. Given its subnanomolar binding affinity and prolonged ocular residence, Cp40-KKK constitutes a promising drug candidate for ocular pathologies underpinned by deregulated C3 activation.},
	issn = {1521-7035},
	doi = {10.1016/j.clim.2020.108391},
	author = {Hughes, Sarah and Gumas, Justin and Lee, Rebecca and Rumano, Merita and Berger, Nadja and Gautam, Avneesh Kumar and Sfyroera, Georgia and Chan, Anna Lorena and Gnanaguru, Gopalan and Connor, Kip M and Kim, Benjamin J and Dunaief, Joshua L and Ricklin, Daniel and Hajishengallis, George and Yancopoulou, Despina and Reis, Edimara S and Mastellos, Dimitrios C and Lambris, John D}
}
@article {1653587,
	title = {Association Between Parental Leave and Ophthalmology Resident Physician Performance},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {11},
	year = {2022},
	month = {2022 Nov 01},
	pages = {1066-1075},
	abstract = {IMPORTANCE: Although parental leave is essential in enhancing resident wellness and fostering inclusive workplace environments, residents may often feel discouraged from using parental leave owing to perceived stigma and concerns about possible negative effects on their training. OBJECTIVE: To examine parental leave usage across multiple institutions and compare residency performance metrics between residents who took parental leave vs their peers who did not take leave. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional analysis conducted from April 1, 2020, to July 28, 2022, of educational records. Multicenter data were obtained from 10 Accreditation Council for Graduate Medical Education (ACGME)-accredited ophthalmology programs across the US. Included ophthalmology residents graduated between 2015 and 2019. Data were analyzed from August 15, 2021, to July 25, 2022. EXPOSURES: Performance metrics of residents who used parental leave during residency were compared with those of residents who did not take parental leave. MAIN OUTCOMES AND MEASURES: Measures of performance included the Ophthalmic Knowledge Assessment Program (OKAP) scores, ACGME milestones scores, board examination pass rates, research activity, and surgical volumes. RESULTS: Of the 283 ophthalmology residents (149 male [52.7\%]) included in the study, 44 (15.5\%) took a median (IQR) parental leave of 4.5 (2-6) weeks. There were no differences in average OKAP percentiles, research activity, average ACGME milestones scores, or surgical volume between residents who took parental leave and those who did not. Residents who pursued fellowship were less likely to have taken parental leave (odds ratio [OR], 0.43; 95\% CI, 0.27-0.68; P \&lt; .001), and residents who practiced in private settings after residency were more likely to have taken parental leave (OR, 3.56; 95\% CI, 1.79-7.08; P \&lt; .001). When stratified by sex, no differences were identified in performance between female residents who took parental leave compared with residents who did not take leave, except a mild surgical number difference in 1 subspecialty category of keratorefractive procedures (difference in median values, -2; 95\% CI, -3.7 to -0.3; P = .03). CONCLUSIONS AND RELEVANCE: In this multicenter cross-sectional study, no differences in performance metrics were identified between residents taking parental leave compared with their peers. These findings may provide reassurance to trainees and program directors regarding the unlikelihood, on average, that taking adequate parental leave will affect performance metrics adversely.},
	keywords = {Cross-Sectional Studies, Education, Medical, Graduate, Female, Humans, Internship and Residency, Male, Ophthalmology, Parental Leave, Physicians, Retrospective Studies, United States},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.3778},
	author = {Huh, Dana D and Wang, Jiangxia and Fliotsos, Michael J and Beal, Casey J and Boente, Charline S and Wisely, C Ellis and De Andrade, Lindsay M and Lorch, Alice C and Ramanathan, Saras and Reinoso, Maria A and Swamy, Ramya N and Waxman, Evan L and Woreta, Fasika A and Srikumaran, Divya}
}
@article {1549013,
	title = {Intrinsic Optical Properties of Boston Keratoprosthesis},
	journal = {Transl Vis Sci Technol},
	volume = {9},
	number = {12},
	year = {2020},
	month = {2020 Nov},
	pages = {10},
	abstract = {Purpose: To benchmark the optical performance of Boston Keratoprosthesis (B-KPro). Methods: Back focal lengths (BFL) of B-KPros for various eye axial lengths were measured using an optical bench, International Organization for Standardization-certified for intraocular lens characterization, and compared against manufacturer{\textquoteright}s specification. The modulation transfer function (MTF) and the resolution efficiencies were measured. The theoretical geometry-dependent higher-order aberrations (HOA) were calculated. The devices were characterized with optical profilometry for estimating the surface scattering. Aberration correction and subsequent image quality improvement were simulated in CODE-V. Natural scene-imaging was performed in a mock ocular environment. Retrospective analysis of 15 B-KPro recipient eyes were presented to evaluate the possibility of achieving 20/20 best-corrected visual acuity (BCVA). Results: BFL measurements were in excellent agreement with the manufacturer-reported values (r = 0.999). The MTF specification exceeded what is required for achieving 20/20 visual acuity. Astigmatism and field curvature, correctable in simulations, were the primary aberrations limiting imaging performance. Profilometry of the anterior surface revealed nanoscale roughness (root-mean-square amplitude, 30-50 nm), contributing negligibly to optical scattering. Images of natural scenes obtained with a simulated B-KPro eye demonstrated good central vision, with 10/10 visual acuity (equivalent to 20/20). Full restoration of 20/20 BCVA was obtainable for over 9 years in some patients. Conclusions: Theoretical and experimental considerations demonstrate that B-KPro has the optical capacity to restore 20/20 BCVA in patients. Further image quality improvement can be anticipated through correction of HOAs. Translational Relevance: We establish an objective benchmark to characterize the optics of the B-KPro and other keratoprosthesis and propose design changes to allow improved vision in B-KPro patients.},
	issn = {2164-2591},
	doi = {10.1167/tvst.9.12.10},
	author = {Hui, Pui-Chuen and Pereira, Leonardo A and Dore, Renald and Chen, Shengtong and Taniguchi, Elise and Chodosh, James and Dohlman, Claes H and Paschalis, Eleftherios I}
}
@article {1504075,
	title = {Implantable self-aligning fiber-optic optomechanical devices for in vivo intraocular pressure-sensing in artificial cornea},
	journal = {J Biophotonics},
	volume = {13},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {e202000031},
	abstract = {Artificial cornea is an effective treatment of corneal blindness. Yet, intraocular pressure (IOP) measurements for glaucoma monitoring remain an urgent unmet need. Here, we present the integration of a fiber-optic Fabry-Perot pressure sensor with an FDA-approved keratoprosthesis for real-time IOP measurements using a novel strategy based on optical-path self-alignment with micromagnets. Additionally, an alternative noncontact sensor-interrogation approach is demonstrated using a bench-top optical coherence tomography system. We show stable pressure readings with low baseline drift (\&lt;2.8 mm Hg) for \&gt;4.5 years in vitro and efficacy in IOP interrogation in vivo using fiber-optic self-alignment, with good initial agreement with the actual IOP. Subsequently, IOP drift in vivo was due to retroprosthetic membrane (RPM) formation on the sensor secondary to surgical inflammation (more severe in the current pro-fibrotic rabbit model). This study paves the way for clinical adaptation of optical pressure sensors with ocular implants, highlighting the importance of controlling RPM in clinical adaptation.},
	issn = {1864-0648},
	doi = {10.1002/jbio.202000031},
	author = {Hui, Pui-Chuen and Shtyrkova, Katia and Zhou, Chengxin and Chen, Xiaoniao and Chodosh, James and Dohlman, Claes H and Paschalis, Eleftherios I}
}
@article {1364615,
	title = {Role of OCT in the diagnosis and management of macular edema from uveitis},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {236-41},
	abstract = {Uveitis is a potentially visually threatening disease accounting for 10\% of vision loss in the developed world. The most common cause of vision loss in patients with uveitis has been shown to be macular edema (ME). The early detection and management of ME is critical to preserve vision in these patients. Optical coherence tomography (OCT) is a valuable tool in the management of many ocular diseases. The use of OCT has revolutionized the diagnosis and management of macular edema from a wide variety of ophthalmological diseases, including uveitis. In this review, we evaluate the role of OCT in the diagnosis and management of uveitic macular edema.},
	keywords = {Humans, Macular Edema, Tomography, Optical Coherence, Uveitis},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.708813},
	author = {Hunter, Rebecca S and Skondra, Dimitra and Papaliodis, George and Sobrin, Lucia}
}
@article {1688331,
	title = {Comment on, "The blinq Vision Screener in Detection of Amblyopia and Strabismus"},
	journal = {Am J Ophthalmol},
	year = {2023},
	month = {2023 Apr 07},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.03.031},
	author = {Hunter, David G}
}
@article {382401,
	title = {Treatment of amblyopia: the "eye pad," or the iPad?},
	journal = {J AAPOS},
	volume = {19},
	number = {1},
	year = {2015},
	month = {2015 Feb},
	pages = {1-2},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2015.01.003},
	author = {Hunter, David G}
}
@article {1635661,
	title = {Enhancing comparison of different vision screening approaches},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Mar 18},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.02.001},
	author = {Hunter, David G}
}
@article {1323928,
	title = {Improving Access-but Not Outcomes-With Iris Optical Coherence Tomography Angiography},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {9},
	year = {2018},
	month = {2018 Sep 01},
	pages = {1045-1046},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.2748},
	author = {Hunter, David G}
}
@article {1109806,
	title = {Central serous chorioretinopathy following medial transposition of split lateral rectus muscle for complete oculomotor nerve palsy},
	journal = {J AAPOS},
	volume = {21},
	number = {6},
	year = {2017},
	month = {2017 Dec},
	pages = {517-518},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2017.06.005},
	author = {Hunter, David G and Yonekawa, Yoshihiro and Shah, Ankoor S and Dagi, Linda R}
}
@article {1532378,
	title = {Validation of the Birefringent Amblyopia Screener (Retinal Polarization Scanner), the Rebion Blinq.{\texttrademark} [Letter]},
	journal = {Clin Ophthalmol},
	volume = {14},
	year = {2020},
	month = {2020},
	pages = {2599-2600},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S276488},
	author = {Hunter, David G}
}
@article {1363121,
	title = {Accuracy of vision screening},
	journal = {J AAPOS},
	volume = {17},
	number = {6},
	year = {2013},
	month = {2013 Dec},
	pages = {652-3},
	keywords = {Amblyopia, Diagnostic Techniques, Ophthalmological, Female, Humans, Male, Strabismus},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2013.07.006},
	author = {Hunter, David G}
}
@article {882946,
	title = {Evaluation of the Risk of Postoperative Infection in Adjustable Suture Strabismus Surgery.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {10},
	year = {2016},
	month = {2016 Oct 1},
	pages = {1156-1157},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.2943},
	author = {Hunter, David G}
}
@article {1782446,
	title = {Richard Moore Robb, MD},
	journal = {J AAPOS},
	year = {2023},
	month = {2023 Nov 27},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.11.004},
	author = {Hunter, David G}
}
@article {1664987,
	title = {A Review on the Use of the Educational Value Unit (EVU) among Teaching Hospitals},
	journal = {Healthcare (Basel)},
	volume = {11},
	number = {1},
	year = {2023},
	month = {2023 Jan 01},
	abstract = {(1) Background: In recent years, medical institutions across the U.S. have implemented a points system based on the Educational Value Unit (EVU) to assess and reward faculty for their educational efforts. The purpose of this narrative review is to summarize the current literature on EVU systems and to evaluate their utility in the U.S. healthcare system. (2) Methods: We searched the Ovid MEDLINE, Embase, Web of Science, and PubMed databases to identify literature describing the inception of EVU systems and current systems implemented by U.S. academic medical centers and medical schools. In total, a combined 48 studies and abstracts pertaining to EVU systems were reviewed, and a combined 26 published studies and abstracts from 1999 to 2022 pertaining to EVU systems were included. (3) Results: To our knowledge, at least 40 U.S. academic medical centers have used an educational metrics system, of which 21 institutions have published studies describing EVU systems in one or more of their medical departments. The outcomes associated with these self-described EVU systems are the focus of this study. EVU systems increase the number of faculty who meet baseline educational requirements, promote educational productivity, redistribute educational burden and funding among faculty members, and shift physician priorities towards education. The monetary reward associated with EVU systems is unlikely to be a significant factor contributing to these changes; instead, intrinsic motivation and a sense of academic responsibility play a larger role. (4) Conclusions: EVU systems are an effective way to evaluate and reward individual and departmental educational efforts in U.S. academic medical centers and medical schools. The adoption of EVUs will likely become more commonplace as U.S. academic medical centers and medical schools place additional emphasis on medical education.},
	issn = {2227-9032},
	doi = {10.3390/healthcare11010136},
	author = {Husain, Alina and Chen, Darren A and Lelli, Gary J}
}
@article {1798421,
	title = {Impact of the Coronavirus Disease 2019 Pandemic on Surgical Volumes Among Fellowship-Trained Glaucoma Subspecialists},
	journal = {J Glaucoma},
	volume = {33},
	number = {1},
	year = {2024},
	month = {2024 Jan 01},
	pages = {35-39},
	abstract = {PRCIS: The change in glaucoma surgical volumes due to the coronavirus disease 2019 pandemic was not uniform across procedure types and was unequal between rural and urban practice locations.

PURPOSE: To quantify the impact of the coronavirus disease 2019 pandemic on surgical volumes performed by fellowship-trained glaucoma subspecialists.

MATERIALS AND METHODS: This retrospective cohort analysis of the Centers for Medicare and Medicaid Services Medicare Public Use File extracted all glaucoma surgeries, including microinvasive glaucoma surgeries (MIGSs), trabeculectomy, goniotomy, lasers, and cataract surgery, performed by fellowship-trained glaucoma surgeons in rural and urban areas between 2016 and 2020. Predicted estimates of 2020 surgical volumes were created utilizing linear squares regression. Percentage change between predicted and observed 2020 surgical volume estimates was analyzed. Statistical significance was achieved at P \&lt;0.05.

RESULTS: In 2020, fellowship-trained glaucoma surgeons operated mostly in urban areas (N = 810, 95\%). A 29\% and 31\% decrease in predicted cataract surgery volumes in urban and rural areas, respectively, was observed. Glaucoma surgeries experienced a 36\% decrease from predicted estimates (N = 56,781). MIGS experienced an 86\% and 75\% decrease in rural and urban areas, respectively. Trabeculectomy in rural areas experienced a 16\% increase relative to predicted estimates while urban areas experienced a decrease of 3\% ( P \&gt; 0.05). The number of goniotomies decreased by 10\% more in rural areas than in urban areas (-22\% and -12\%, respectively). Laser procedures decreased by 8\% more in urban areas than in rural areas (-18\% and -10\%, respectively).

CONCLUSIONS: Among glaucoma-trained surgeons, glaucoma surgeries experienced a greater volume loss than cataract surgeries. In urban US areas, relative reductions in MIGS and goniotomy volumes in urban areas may have been compensated by greater laser and trabeculectomy volumes. Trabeculectomies in rural areas were the only group exceeding predicted estimates. Glaucoma subspecialists may utilize these findings when planning for future events and in overcoming any remaining unmet need in terms of glaucoma care.},
	keywords = {Aged, Cataract, COVID-19, Fellowships and Scholarships, Glaucoma, Humans, Intraocular Pressure, Medicare, Pandemics, Retrospective Studies, Trabeculectomy, United States},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002269},
	author = {Hussain, Zain S and Andoh, Joana E and Loya, Asad and Yousefi, Siamak and Boland, Michael V}
}
@article {1435403,
	title = {3D in vitro model for human corneal endothelial cell maturation},
	journal = {Exp Eye Res},
	volume = {184},
	year = {2019},
	month = {2019 Jul},
	pages = {183-191},
	abstract = {Corneal endothelium is a cellular monolayer positioned on the Descemet{\textquoteright}s membrane at the anterior cornea, and it plays a critical role in maintaining corneal clarity. Our present study examines the feasibility of utilizing our 3-dimensional (3D) corneal stromal construct, which consists of human corneal fibroblasts (HCF) and their self-assembled matrix, to observe the development and maturation of human corneal endothelial cells (HCEndoCs) in a co-culture model. Three-dimensional HCF constructs were created by growing the HCFs on Transwell membranes in Eagles{\textquoteright} minimum essential medium (EMEM)\&nbsp;+\&nbsp;10\% FBS\&nbsp;+\&nbsp;0.5\&nbsp;mM Vitamin C (VitC) for about 4 weeks. HCEndoCs, either primary (pHCEndoC) or cell line (HCEndoCL), were either seeded in chamber slides, directly on the Transwell membranes, or on the 3D HCF constructs and cultivated for 5 days or 2 weeks. The HCEndoCs that were seeded directly on the Transwell membranes were exposed indirectly to HCF by culturing the HCF on the plate beneath the membrane. Cultures were examined for morphology and ultrastructure using light and transmission electron microscopy (TEM). In addition, indirect-immunofluorescence microscopy (IF) was used to examine tight junction formation (ZO-1), maturation (ALDH1A1), basement membrane formation (Laminin), cell proliferation (Ki67), cell death (caspase-3), and fibrotic response (CTGF). As expected, both pHCEndoCs and HCEndoCLs formed monolayers on the constructs; however, the morphology of the HCEndoCLs appeared to be similar to that seen in vivo, uniform and closely packed, whereas the pHCEndoCs remained elongated. The IF data showed that laminin localization was present in the HCEndoCs{\textquoteright} cytoplasm as cell-cell contact increased, and when they were grown in the 3D co-culture, the beginnings of what appears to be a continuous DM-like structure was observed. In addition, in co-cultures, ALDH1A1-positive HCEndoCs were present, ZO-1 expression localized within the tight junctions, minimal numbers of HCEndoCs were Ki67-or Caspase-3-positive, and CTGF was positive in both the HCEndoCs cytoplasm and the matrix of the co-culture. Also, laminin localization was stimulated in HCEndoCs upon indirect stimuli secreted by HCF. The present data suggests our 3D co-culture model is useful for studying corneal endothelium maturation in vitro since the co-culture promotes new DM-like formation, HCEndoCs develop in vivo-like characteristics, and the fibrotic response is activated. Our current findings are applicable to understanding the implications of corneal endothelial injection therapy, such as if the abnormal DM has to be removed from the patient, the newly injected endothelial cells will seed onto the wound area and deposit a new DM-like membrane. However, caution should be observed and as much of the normal DM should be left intact since removal of the DM can cause a posterior stromal fibrotic response.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.04.003},
	author = {Hutcheon, Audrey E K and Zieske, James D and Guo, Xiaoqing}
}
@article {688621,
	title = {Clinical Models and Algorithms for the Prediction of Retinopathy of Prematurity: A Report by the American Academy of Ophthalmology.},
	journal = {Ophthalmology},
	volume = {123},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {804-16},
	abstract = {OBJECTIVE: To assess the accuracy with which available retinopathy of prematurity (ROP) predictive models detect clinically significant ROP and to what extent and at what risk these models allow for the reduction of screening examinations for ROP. METHODS: A literature search of the PubMed and Cochrane Library databases was conducted last on May 1, 2015, and yielded 305 citations. After screening the abstracts of all 305 citations and reviewing the full text of 30 potentially eligible articles, the panel members determined that 22 met the inclusion criteria. One article included 2 studies, for a total of 23 studies reviewed. The panel extracted information about study design, study population, the screening algorithm tested, interventions, outcomes, and study quality. The methodologist divided the studies into 2 categories-model development and model validation-and assigned a level of evidence rating to each study. One study was rated level I evidence, 3 studies were rated level II evidence, and 19 studies were rated level III evidence. RESULTS: In some cohorts, some models would have allowed reductions in the number of infants screened for ROP without failing to identify infants requiring treatment. However, the small sample size and limited generalizability of the ROP predictive models included in this review preclude their widespread use to make all-or-none decisions about whether to screen individual infants for ROP. As an alternative, some studies proposed approaches to apply the models to reduce the number of examinations performed in low-risk infants. CONCLUSIONS: Additional research is needed to optimize ROP predictive model development, validation, and application before such models can be used widely to reduce the burdensome number of ROP screening examinations.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.11.003},
	author = {Hutchinson, Amy K and Melia, Michele and Yang, Michael B and VanderVeen, Deborah K and Wilson, Lorri B and Lambert, Scott R}
}
@article {1323929,
	title = {The Use of β-Blockers for the Treatment of Periocular Hemangiomas in Infants: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {126},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {146-155},
	abstract = {PURPOSE: To review the published literature assessing the efficacy of β-blockers for the treatment of periocular hemangioma in infants. METHODS: Literature searches were conducted in May 2018 in PubMed with no date restrictions and limited to studies published in English and in the Cochrane Library database without any restrictions. The combined searches yielded 437 citations. Of these,16 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. RESULTS: None of the 16 studies included in this assessment were rated level I, 3 were rated level II, and 13 were rated level III. The most common treatment regimen was 2 mg/kg daily oral propranolol, but intralesional and topical β-blockers were also used. Treatment effect was most often measured in terms of reduction in the size of the lesions, which occurred in the majority of patients. β-Blockers were consistently shown to reduce astigmatism, but this reduction was shown to be statistically significant in only 2 series. The effect of β-blockers on amblyopia was not adequately documented. β-Blockers were generally well tolerated and had mild side effects (fatigue, gastrointestinal upset/diarrhea, restlessness/sleep disturbances, minor wheezing, and cold extremities). Complications severe enough to require cessation of treatment occurred in only 2 patients out of a total of 229 who received β-blockers. CONCLUSIONS: There is limited evidence to support the safety and efficacy of both topical and systemic β-blockers to promote regression of periocular hemangiomas. Additional research may confirm the best dosage and route of administration to maximize efficacy in reducing induced astigmatism and amblyopia associated with periocular hemangiomas while minimizing side effects.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.07.023},
	author = {Hutchinson, Amy K and Kraker, Raymond T and Pineles, Stacy L and VanderVeen, Deborah K and Wilson, Lorri B and Galvin, Jennifer A and Lambert, Scott R}
}
@article {1470970,
	title = {Five-Year Cost-effectiveness of Intravitreous Ranibizumab Therapy vs Panretinal Photocoagulation for Treating Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Oct 24},
	pages = {1-9},
	abstract = {Importance: The DRCR Retina Network Protocol S randomized clinical trial suggested that the mean visual acuity of eyes with proliferative diabetic retinopathy (PDR) treated with ranibizumab is not worse at 5 years than that of eyes treated with panretinal photocoagulation (PRP). Moreover, the ranibizumab group had fewer new cases of diabetic macular edema (DME) with vision loss or vitrectomy but had 4 times the number of injections and 3 times the number of visits. Although 2-year cost-effectiveness results of Protocol S were previously identified, incorporating 5-year data from Protocol S could alter the longer-term cost-effectiveness of the treatment strategies from the perspective of the health care system. Objective: To evaluate 5- and 10-year cost-effectiveness of therapy with ranibizumab, 0.5 mg, compared with PRP for treating PDR. Design, Setting, and Participants: A preplanned secondary analysis of the Protocol S randomized clinical trial using efficacy, safety, and resource utilization data through 5 years of follow-up for 213 adults diagnosed with PDR and simulating results through 10 years. Interventions: Intravitreous ranibizumab, 0.5 mg, at baseline and as frequently as every 4 weeks based on a structured retreatment protocol vs PRP at baseline for PDR; eyes in both groups could receive ranibizumab for concomitant DME with vision loss. Main Outcomes and Measures: Incremental cost-effectiveness ratios (ICERs) of ranibizumab therapy compared with PRP were evaluated for those with and without center-involved DME (CI-DME) and vision loss (Snellen equivalent, 20/32 or worse) at baseline. Results: The study included 213 adults with a mean (SD) age of 53 (12) years, of whom 92 (43\%) were women and 155 (73\%) were white. The ICER of the ranibizumab group compared with PRP for patients without CI-DME at baseline was $582 268 per quality-adjusted life-year (QALY) at 5 years and $742 202/QALY at 10 years. For patients with baseline CI-DME, ICERs were $65 576/QALY at 5 years and $63 930/QALY at 10 years. Conclusions and Relevance: This study suggests that during 5 to 10 years of treatment, ranibizumab, 0.5 mg, as given in the studied trial compared with PRP may be within the frequently cited range considered cost-effective in the United States for eyes presenting with PDR and vision-impairing CI-DME, but not for those with PDR but without vision-impairing CI-DME. Substantial reductions in anti-vascular endothelial growth factor cost may make the ranibizumab therapy cost-effective within this range even for patients without baseline CI-DME. Trial Registration: ClinicalTrials.gov identifier: NCT01489189.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.4284},
	author = {Hutton, David W and Stein, Joshua D and Glassman, Adam R and Bressler, Neil M and Jampol, Lee M and Sun, Jennifer K and DRCR Retina Network}
}
@article {1667707,
	title = {Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {3},
	year = {2023},
	month = {2023 Mar 01},
	pages = {268-274},
	abstract = {IMPORTANCE: The DRCR Retina Network Protocol AC showed no significant difference in visual acuity outcomes over 2 years between treatment with aflibercept monotherapy and bevacizumab first with switching to aflibercept for suboptimal response in treating diabetic macular edema (DME). Understanding the estimated cost and cost-effectiveness of these approaches is important. OBJECTIVE: To evaluate the cost and cost-effectiveness of aflibercept monotherapy vs bevacizumab-first strategies for DME treatment. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation was a preplanned secondary analysis of a US randomized clinical trial of participants aged 18 years or older with center-involved DME and best-corrected visual acuity of 20/50 to 20/320 enrolled from December 15, 2017, through November 25, 2019. INTERVENTIONS: Aflibercept monotherapy or bevacizumab first, switching to aflibercept in eyes with protocol-defined suboptimal response. MAIN OUTCOMES AND MEASURES: Between February and July 2022, the incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-year (QALY) over 2 years was assessed. Efficacy and resource utilization data from the randomized clinical trial were used with health utility mapping from the literature and Medicare unit costs. RESULTS: This study included 228 participants (median age, 62 [range, 34-91 years; 116 [51\%] female and 112 [49\%] male; 44 [19\%] Black or African American, 60 [26\%] Hispanic or Latino, and 117 [51\%] White) with 1 study eye. The aflibercept monotherapy group included 116 participants, and the bevacizumab-first group included 112, of whom 62.5\% were eventually switched to aflibercept. Over 2 years, the cost of aflibercept monotherapy was $26 504 (95\% CI, $24 796-$28 212) vs $13 929 (95\% CI, $11 984-$15 874) for the bevacizumab-first group, a difference of $12 575 (95\% CI, $9987-$15 163). The aflibercept monotherapy group gained 0.015 (95\% CI, -0.011 to 0.041) QALYs using the better-seeing eye and had an ICER of $837 077 per QALY gained compared with the bevacizumab-first group. Aflibercept could be cost-effective with an ICER of $100 000 per QALY if the price per dose were $305 or less or the price of bevacizumab was $1307 per dose or more. CONCLUSIONS AND RELEVANCE: Variability in individual needs will influence clinician and patient decisions about how to treat specific eyes with DME. While the bevacizumab-first group costs still averaged approximately $14 000 over 2 years, this approach, as used in this study, may confer substantial cost savings on a societal level without sacrificing visual acuity gains over 2 years compared with aflibercept monotherapy.},
	keywords = {Aged, Angiogenesis Inhibitors, Bevacizumab, Cost-Benefit Analysis, Diabetes Mellitus, Diabetic Retinopathy, Female, Humans, Macular Edema, Male, Medicare, Middle Aged, Ranibizumab, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins, United States, Vascular Endothelial Growth Factor A},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.6142},
	author = {Hutton, David W and Glassman, Adam R and Liu, Danni and Sun, Jennifer K and DRCR Retina Network}
}
@article {1586173,
	title = {Costs of Managing Diabetic Macular Edema with Good Visual Acuity with Aflibercept, Laser or Observation: DRCR Retina Network Protocol V},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 Mar 10},
	abstract = {PURPOSE: Since eyes with center-involved diabetic macular edema (CI-DME) and good baseline visual acuity (VA) showed no difference in VA loss when managed initially with observation, laser, or aflibercept, understanding the estimated costs of these strategies to the US population is relevant for health care planning. DESIGN: Pre-planned subgroup analysis from a randomized controlled trial METHODS, SETTING, AND PARTICIPANTS: Total costs for managing participants with CI-DME and good baseline VA assigned to aflibercept (n= 236), laser (n=240), or observation (n = 236) during the 2-year trial were calculated. Using epidemiological data and extrapolating costs, 10-year costs for caring for persons with CI-DME and good baseline VA throughout the US was estimated. INTERVENTIONS: Observation or laser groups initiated aflibercept if VA decreased. Aflibercept group received injections up to every 4 weeks. MAIN OUTCOMES AND MEASURES: Estimated 10-year U.S. population costs to manage CI-DME with good VA. RESULTS: Assuming all patients in the US with CI-DME and good baseline VA received aflibercept initially, 10-year costs were projected to be $28.80 billion compared with $14.42 billion if initially receiving laser treatment or $15.70 billion if initially observed, with aflibercept added if VA worsened in the laser or observation arms. CONCLUSIONS AND RELEVANCE: Similar VA outcomes on average are obtained by initially managing CI-DME and good baseline VA with laser or observation strategies instead of immediately using aflibercept. While any one of these three strategies might be warranted depending on an individual{\textquoteright}s specific circumstances, on a societal level, cost savings might be achieved with these first two approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01909791.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.02.033},
	author = {Hutton, David W and Glassman, Adam R and Stein, Joshua D and Bressler, Neil M and Sun, Jennifer K and DRCR Retina Network}
}
@article {935676,
	title = {Dilated fundus exam and associated findings in spontaneous subconjunctival haemorrhage},
	journal = {Acta Ophthalmol},
	volume = {95},
	number = {5},
	year = {2017},
	month = {2017 Aug},
	pages = {e432-e433},
	issn = {1755-3768},
	doi = {10.1111/aos.13309},
	author = {Huynh, Nancy and Wang, Jay and Vavvas, Demetrios}
}
@article {1364616,
	title = {Intravitreal triamcinolone for cancer-associated retinopathy refractory to systemic therapy},
	journal = {J Ophthalmic Inflamm Infect},
	volume = {2},
	number = {3},
	year = {2012},
	month = {2012 Sep},
	pages = {169-71},
	abstract = {PURPOSE: The purpose of this study is to report the use of intravitreal triamcinolone for treatment of cancer-associated retinopathy (CAR) refractory to systemic therapy. METHODS: This was a retrospective chart review study. RESULTS: A 67-year-old man presented with cancer-associated retinopathy with antibodies against a 46-kDa retinal protein, alpha enolase. There was disease progression despite therapy with mycophenolate and intravenous immunoglobulin. Serial intravitreal injections of triamcinolone resulted in restoration of photoreceptor anatomy on optical coherence tomography and visual improvement. The patient{\textquoteright}s vision was preserved at 20/40 OD and 20/32 OS until his death from lung cancer 31\&nbsp;months after CAR diagnosis. CONCLUSIONS: Intravitreal triamcinolone may be beneficial for maintenance of vision in patients with CAR.},
	issn = {1869-5760},
	doi = {10.1007/s12348-012-0067-9},
	author = {Huynh, Nancy and Shildkrot, Yevgeniy and Lobo, Ann-Marie and Sobrin, Lucia}
}
@article {1773621,
	title = {Ophthalmic Manifestations of Unilateral Coronal Synostosis},
	journal = {Curr Eye Res},
	volume = {48},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {879-886},
	abstract = {PURPOSE: To summarize the ophthalmic manifestations of unilateral coronal synostosis patients. METHODS: We performed a literature search in the electronic database of PubMed, CENTRAL, Cochrane, and Ovid Medline guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement for studies evaluating ophthalmic manifestations of unilateral coronal synostosis. RESULTS: Unilateral coronal synostosis, also called unicoronal synostosis, may be mistaken for deformational plagiocephaly, an asymmetric skull flattening common in newborns. Characteristic facial features, however, distinguish the two. Ophthalmic manifestations of unilateral coronal synostosis include a "harlequin deformity", anisometropic astigmatism, strabismus, amblyopia, and significant orbital asymmetry. The astigmatism is greater on the side opposite the fused coronal suture. Optic neuropathy is uncommon unless unilateral coronal synostosis accompanies more complex multi-suture craniosynostosis. In many cases, surgical intervention is recommended; without intervention, skull asymmetry and ophthalmic disorders tend to worsen with time. Unilateral coronal synostosis can be managed by early endoscopic stripping of the fused suture and helmeting through a year of age or by fronto-orbital-advancement at approximately 1 year of age. Several studies have demonstrated that anisometropic astigmatism, amblyopia, and severity of strabismus are significantly lower after earlier intervention with endoscopic strip craniectomy and helmeting compared to treatment by fronto-orbital-advancement. It remains unknown whether the earlier timing or the nature of the procedure is responsible for the improved outcomes. As endoscopic strip craniectomy can only be performed in the first few months of life, early recognition of the facial, orbital, eyelid, and ophthalmic characteristics by consultant ophthalmologists enables expeditious referral and optimized ophthalmic outcomes. CONCLUSION: Timely identification of craniofacial and ophthalmic manifestations of infants with unilateral coronal synostosis is important. Early recognition and prompt endoscopic treatment appears to optimize ocular outcomes.},
	keywords = {Amblyopia, Astigmatism, Craniosynostoses, Humans, Infant, Infant, Newborn, Retrospective Studies, Strabismus},
	issn = {1460-2202},
	doi = {10.1080/02713683.2023.2224536},
	author = {Huynh, Elisah M and Elhusseiny, Abdelrahman M and Dagi, Linda R}
}
@article {1364617,
	title = {Decreased vision and junctional scotoma from pituicytoma},
	journal = {Case Rep Ophthalmol},
	volume = {3},
	number = {2},
	year = {2012},
	month = {2012 May},
	pages = {190-6},
	abstract = {Pituicytomas are rare neoplasms of the sellar region. We report a case of vision loss and a junctional scotoma in a 43-year-old woman caused by compression of the optic chiasm by a pituitary tumor. The morphological and immunohistochemical characteristics of the tumor were consistent with the diagnosis of pituicytoma. The tumor was debulked surgically, and the patient{\textquoteright}s vision improved.},
	issn = {1663-2699},
	doi = {10.1159/000339242},
	author = {Huynh, Nancy and Stemmer-Rachamimov, Anat O and Swearingen, Brooke and Cestari, Dean M}
}
@article {1645454,
	title = {Paediatric anterior uveitis management in the USA: a single-centre, 10-year retrospective chart review exploring the efficacy and safety of systemic immunomodulatory therapy},
	journal = {Eye (Lond)},
	volume = {37},
	number = {7},
	year = {2023},
	month = {2023 May},
	pages = {1325-1330},
	abstract = {OBJECTIVE: To evaluate the efficacy of immunomodulatory therapy (IMT) in paediatric anterior uveitis. METHODS: Chart review of all patients <= 18 years treated for anterior uveitis using a stepladder approach during a 10-year period. The type and duration of IMT were noted. The data were analysed depending on chronicity, aetiology, and type of IMT using appropriate statistical tests. The outcome measures included ocular complications, the need for surgical intervention, and visual outcomes. RESULTS: One hundred and thirty-four patients (191 eyes) were analyzed. The median age at diagnosis was 7 years (interquartile range (IQR): 7.5 years). The median follow-up was 4 years (IQR: 6 years). The most common causes of anterior uveitis were Juvenile idiopathic arthritis (64 patients, 47.8\%) and undifferentiated (33 patients,\&nbsp;24.6\%). All patients were started on topical steroids and cycloplegics. 94 (70\%) patients required IMT. 92 (68.6\%) were started on Methotrexate as the first agent, of which 21 (22\%) were switched to a different agent owing to side effects. Biologic agent was added in 55 (41\%) patients. 21 (16\%) required switch to a second biologic agent, 5 (3.7\%) to third, and 1 (0.8\%) to fourth biologic agent. At the last exam, 11 (8\%) had persistent inflammation. 55 (41\%) had ocular complications, and 113 (84\%) had a best corrected visual acuity >= 20/40. CONCLUSION: Early introduction of IMT and switch to different agents may be required to control anterior uveitis and reduce the complications in children. IMT is safe and effective in treating paediatric anterior uveitis.},
	keywords = {Biological Factors, Child, Humans, Immunomodulation, Retrospective Studies, United States, Uveitis, Uveitis, Anterior},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-02121-3},
	author = {Huynh, Elisah and Elhusseiny, Abdelrahman M and Nihalani, Bharti R}
}
@article {1354350,
	title = {Instability of the perceived world while watching 3D stereoscopic imagery: A likely source of motion sickness symptoms},
	journal = {Iperception},
	volume = {5},
	number = {6},
	year = {2014},
	month = {2014},
	pages = {515-35},
	abstract = {Watching 3D content using a stereoscopic display may cause various discomforting symptoms, including eye strain, blurred vision, double vision, and motion sickness. Numerous studies have reported motion-sickness-like symptoms during stereoscopic viewing, but no causal linkage between specific aspects of the presentation and the induced discomfort has been explicitly proposed. Here, we describe several causes, in which stereoscopic capture, display, and viewing differ from natural viewing resulting in static and, importantly, dynamic distortions that conflict with the expected stability and rigidity of the real world. This analysis provides a basis for suggested changes to display systems that may alleviate the symptoms, and suggestions for future studies to determine the relative contribution of the various effects to the unpleasant symptoms.},
	issn = {2041-6695},
	doi = {10.1068/i0647},
	author = {Hwang, Alex D and Peli, Eli}
}
@article {1307453,
	title = {Impact of Oncoming Headlight Glare With Cataracts: A Pilot Study},
	journal = {Front Psychol},
	volume = {9},
	year = {2018},
	month = {2018},
	pages = {164},
	abstract = {Oncoming headlight glare (HLG) reduces the visibility of objects on the road and may affect the safety of nighttime driving. With cataracts, the impact of oncoming HLG is expected to be more severe. We used our custom HLG simulator in a driving simulator to measure the impact of HLG on pedestrian detection by normal vision subjects with simulated mild cataracts and by patients with real cataracts.Five normal vision subjects drove nighttime scenarios under two HLG conditions (with and without HLG: HLGY and HLGN, respectively), and three vision conditions (with plano lens, simulated mild cataract, and optically blurred clip-on). Mild cataract was simulated by applying a 0.8 Bangerter diffusion foil to clip-on plano lenses. The visual acuity with the optically blurred lenses was individually chosen to match the visual acuity with the simulated cataract clip-ons under HLGN. Each nighttime driving scenario contains 24 pedestrian encounters, encompassing four pedestrian types; walking along the left side of the road, walking along the right side of the road, crossing the road from left to right, and crossing the road from right to left. Pedestrian detection performances of five patients with mild real cataracts were measured using the same setup. The cataract patients were tested only in HLGY and HLGN conditions. Participants{\textquoteright} visual acuity and contrast sensitivity were also measured in the simulator with and without stationary HLG.For normal vision subjects, both the presence of oncoming HLG and wearing the simulated cataract clip-on reduced pedestrian detection performance. The subjects performed worst in events where the pedestrian crossed from the left, followed by events where the pedestrian crossed from the right. Significant interactions between HLG condition and other factors were also found: (1) the impact of oncoming HLG with the simulated cataract clip-on was larger than with the plano lens clip-on, (2) the impact of oncoming HLG was larger with the optically blurred clip-on than with the plano lens clip-on, but smaller than with the simulated cataract clip-on, and (3) the impact was larger for the pedestrians that crossed from the left than those that crossed from the right, and for the pedestrians walking along the left side of the road than walking along the right side of the road, suggesting that the pedestrian proximity to the glare source contributed to the performance reduction. Under HLGN, almost no pedestrians were missed with the plano lens or the simulated cataract clip-on (0 and 0.5\%, respectively), but under HLGY, the rate of pedestrian misses increased to 0.5 and 6\%, respectively. With the optically blurred clip-on, the percent of missed pedestrians under HLGN and HLGY did not change much (5\% and 6\%, respectively). Untimely response rate increased under HLGY with the plano lens and simulated cataract clip-ons, but the increase with the simulated cataract clip-on was significantly larger than with the plano lens clip-on. The contrast sensitivity with the simulated cataract clip-on was significantly degraded under HLGY. The visual acuity with the plano lens clip-on was significantly improved under HLGY, possibly due to pupil myosis. The impact of HLG measured for real cataract patients was similar to the impact on performance of normal vision subjects with simulated cataract clip-ons.Even with mild (simulated or real) cataracts, a substantial negative effect of oncoming HLG was measurable in the detection of crossing and walking-along pedestrians. The lowered pedestrian detection rates and longer response times with HLGY demonstrate a possible risk that oncoming HLG poses to patients driving with cataracts.},
	issn = {1664-1078},
	doi = {10.3389/fpsyg.2018.00164},
	author = {Hwang, Alex D and Tuccar-Burak, Merve and Goldstein, Robert and Peli, Eli}
}
@article {1709716,
	title = {Risk Ractors for Strabismus Surgery after Pediatric Cataract Surgery in the United States},
	journal = {Ophthalmol Sci},
	volume = {3},
	number = {2},
	year = {2023},
	month = {2023 Jun},
	pages = {100271},
	abstract = {PURPOSE: To determine the cumulative incidence of strabismus surgery after pediatric cataract surgery and identify the associated risk factors. DESIGN: US population-based insurance claims retrospective cohort study. PARTICIPANTS: Patients <= 18 years old who underwent cataract surgery in 2 large databases: Optum Clinformatics Data Mart (2003-2021) and IBM MarketScan (2007-2016). METHODS: Individuals with at least 6 months of prior enrollment were included, and those with a history of strabismus surgery were excluded. The primary outcome was strabismus surgery within 5 years of cataract surgery. The risk factors investigated included age, sex, persistent fetal vasculature (PFV), intraocular lens (IOL) placement, nystagmus and strabismus diagnoses before cataract surgery, and cataract surgery laterality. MAIN OUTCOME MEASURES: Kaplan-Meier estimated cumulative incidence of strabismus surgery 5 years after cataract surgery and hazard ratios (HRs) with 95\% confidence intervals (CIs) from multivariable Cox proportional hazards regression models. RESULTS: Strabismus surgery was performed on 271/5822 children included in this study. The cumulative incidence of strabismus surgery within 5 years after cataract surgery was 9.6\% (95\% CI, 8.3\%-10.9\%). Children who underwent strabismus surgery were more likely to be of younger age at the time of cataract surgery, of female sex, have a history of PFV or nystagmus, have a pre-existing strabismus diagnosis, and less likely to have an IOL placed (all P \&lt; 0.001). Factors associated with strabismus surgery in the multivariable analysis included age 1 to 4 years (HR, 0.50; 95\% CI, 0.36-0.69; P \&lt; 0.001) and age \&gt; 5 years (HR, 0.13; 95\% CI, 0.09-0.18; P\&nbsp;\&lt;\&nbsp;0.001) compared with age \&lt; 1 year at time of cataract surgery, male sex (HR, 0.75; 95\% CI, 0.59-0.95; P\&nbsp;\&lt;\&nbsp;0.001), IOL placement (HR, 0.71; 95\% CI, 0.54-0.94; P\&nbsp;= 0.016), and strabismus diagnosis before cataract surgery (HR, 4.13; 95\% CI, 3.17-5.38; P \&lt; 0.001). Among patients with strabismus diagnosis before cataract surgery, younger age at cataract surgery was the only factor associated with increased risk of strabismus surgery. CONCLUSIONS: Approximately 10\% of patients will undergo strabismus surgery within 5 years after pediatric cataract surgery. Children of younger age, female sex, and with a pre-existing strabismus diagnosis undergoing cataract surgery without IOL placement are at greater risk. FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100271},
	author = {Hwang, Bryce and Oke, Isdin and Lambert, Scott R}
}
@article {468991,
	title = {Pivotal clinical trials of novel ophthalmic drugs and medical devices: retrospective observational study, 2002-2012.},
	journal = {BMJ Open},
	volume = {5},
	number = {6},
	year = {2015},
	month = {2015},
	pages = {e007987},
	abstract = {OBJECTIVES: Novel therapeutics are an important part of ophthalmologists{\textquoteright} armamentarium, and the risks and benefits of these therapies must be carefully evaluated. We sought to quantify the characteristics of the pivotal clinical trials supporting the regulatory approval of new ophthalmic drugs and medical devices. DESIGN: Retrospective observational study. SETTING AND DATA SOURCE: Medical review dossiers for new ophthalmic drug and high-risk device approvals released publicly by the US Food and Drug Administration (FDA). MAIN OUTCOME MEASURES: Proportion of pivotal trials with randomisation, masking, active or placebo controls and subgroup analyses; total and median number of trial enrollees; and the number of drugs and devices approved with required postapproval studies. RESULTS: From 2002 to 2012, the FDA approved 11 ophthalmic drugs and 25 devices. The pivotal trials underlying the approvals of ophthalmic drugs in our study cohort enrolled a median of 809 patients. Virtually all drug trials were randomised and masked (91\%), of which 7 (70\%) used a placebo control. Pivotal trials for ophthalmic devices enrolled 324 patients on average, and significantly fewer trials for ophthalmic devices versus drugs were randomised (16\% vs 91\%; p\&lt;0.001) or masked (12\% vs 91\%; p\&lt;0.001). 8 (32\%) ophthalmic devices and 6 (55\%) ophthalmic drugs were approved with required postapproval studies. CONCLUSIONS: Ophthalmic therapeutics were approved based on varying levels of evidence. Postapproval studies could be used to confirm or refute early indications of safety and effectiveness of these therapeutics, with the study results accessible to patients and clinicians who need to make informed treatment decisions.},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2015-007987},
	author = {Hwang, Jenny and Hwang, Thomas J and Ciolino, Joseph B}
}
@article {382206,
	title = {Retinal implants and medicare reimbursement policies for breakthrough treatments in ophthalmology.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {4},
	year = {2015},
	month = {2015 Apr 1},
	pages = {373-4},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.54},
	author = {Hwang, Thomas J and Ciolino, Joseph B}
}
@article {1363122,
	title = {Development of a Headlight Glare Simulator for a Driving Simulator},
	journal = {Transp Res Part C Emerg Technol},
	volume = {32},
	year = {2013},
	month = {2013 Jul 01},
	pages = {129-143},
	abstract = {We describe the design and construction of a headlight glare simulator to be used with a driving simulator. The system combines a modified programmable off-the-shelf LED display board and a beamsplitter so that the LED lights, representing the headlights of oncoming cars, are superimposed over the driving simulator headlights image. Ideal spatial arrangement of optical components to avoid misalignments of the superimposed images is hard to achieve in practice and variations inevitably introduce some parallax. Furthermore, the driver{\textquoteright}s viewing position varies with driver{\textquoteright}s height and seating position preferences exacerbate such misalignment. We reduce the parallax errors using an intuitive calibration procedure (simple drag-and-drop alignment of nine LED positions with calibration dots on the screen). To simulate the dynamics of headlight brightness changes when two vehicles are approaching, LED intensity control algorithms based on both headlight and LED beam shapes were developed. The simulation errors were estimated and compared to real-world headlight brightness variability.},
	issn = {0968-090X},
	doi = {10.1016/j.trc.2012.09.003},
	author = {Hwang, Alex D and Peli, Eli}
}
@article {1460375,
	title = {Comparison of Pedestrian Detection With and Without Yellow-Lens Glasses During Simulated Night Driving With and Without Headlight Glare},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Aug 01},
	abstract = {Importance: Some marketing materials for yellow-lens night-driving glasses claim that they increase nighttime road visibility and reduce oncoming headlight glare (HLG). However, there is no scientific evidence to support these claims. Objective: To measure the association between yellow-lens glasses and the detection of pedestrians with and without an oncoming HLG, using a driving simulator equipped with a custom HLG simulator. Design, Setting, and Participants: A single-center cohort study was conducted between September 8, 2016, and October 25, 2017, at the Schepens Eye Research Institute. A total of 22 individuals participated in the study, divided into groups to determine response to a pedestrian wearing a navy blue shirt by younger individuals and, to control for participant{\textquoteright}s age and the interaction of the shirt color with the filter, response to a pedestrian wearing an orange shirt by a group of younger and older participants. Exposures: Participants drove scripted night-driving scenarios, 3 times with 3 commercially available yellow-lens glasses and once with clear-lens glasses, with the HLG simulator turned on and off. A total of 8 conditions were used for each participant. Main Outcomes and Measures: Pedestrian detection response time. Results: The 22 participants who completed the study included 12 younger (mean [SD] age, 28 [7] years; 6 men) individuals who responded to a pedestrian wearing a dark navy blue shirt, as well as 6 younger (mean [SD] age, 27 [4] years; 4 men) and 4 older (mean [SD], 70 [11] years; all men) participants who responded to a pedestrian in an orange shirt. All participants had normal visual acuity (mean [SD], -0.05 [0.06] logMAR). No significant difference in response time with yellow lens was found in all experiment conditions; younger participants for dark navy blue shirt pedestrians (F1,33 = 0.59; P = .45), orange shirt pedestrians (F1,15 = 0.13; P = .72), and older participants for orange shirt pedestrians (F1,9 = 0.84; P = .38). Among all participants (n = 22), no significant main effect of yellow lenses was found (F1,63 = 0.64; P = .42). In all measuring conditions, the response times with the yellow lenses were not better than with the clear lenses. Significant main effects of HLG were found with dark navy blue shirt pedestrian condition for young participants (F1,33 = 7.34; P \&lt; .001) and with orange shirt pedestrian condition for older individuals (F1,9 = 75.32; P \&lt; .001), where the difference in response time between with and without HLG was larger for older (1.5 seconds) than younger (0.3 seconds) participants. Conclusions and Relevance: Using a driver simulator equipped with an HLG simulator, yellow-lens night-driving glasses did not appear to improve pedestrian detection at night or reduce the negative effects of HLG on pedestrian detection performance. These findings do not appear to support having eye care professionals advise patients to use yellow-lens night-driving glasses.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.2893},
	author = {Hwang, Alex D and Tuccar-Burak, Merve and Peli, Eli}
}
@article {680416,
	title = {Increased Intraocular Pressure and Hyperglycemic Level in Diabetic Patients.},
	journal = {PLoS One},
	volume = {11},
	number = {3},
	year = {2016},
	month = {2016},
	pages = {e0151833},
	abstract = {PURPOSE: To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: A retrospective chart review was performed on subjects with a diagnosis of NPDR and a corresponding HbA1c level measured within 90 days before or after an IOP measurement over a two-year period. Exclusion criteria included a diagnosis of glaucoma or treatment with IOP lowering medications or oral or topical steroids. RESULTS: Using 14.5mmHg as a baseline mean value for IOP, 42 subjects had an IOP \&lt; 14.5mmHg and mean HbA1c of 8.1{\textpm}1.1, while 72 subjects had an IOP >= 14.5mmHg and a mean HbA1c of 9.0{\textpm}2.1. Although there was an overlap in the confidence intervals, a significant difference (P = 0.01) in the mean HbA1c level was observed in regression analysis between the two groups. Importantly, diabetic subjects with elevated HbA1c levels rarely (\&lt;1\%) exhibited reduced IOP levels. CONCLUSIONS: Diabetic subjects with elevated HbA1c levels exhibited significantly higher IOPs compared to those with lower HbA1c levels. Findings from this study indicate an association between hyperglycemia and elevated IOP and that poor glycemic control may contribute to increased IOP levels in long-term diabetic patients.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0151833},
	author = {Hymowitz, Maggie B and Chang, Donny and Feinberg, Edward B and Roy, Sayon}
}
@article {1642018,
	title = {Hyaluronic acid in the treatment of dry eye disease},
	journal = {Acta Ophthalmol},
	volume = {100},
	number = {8},
	year = {2022},
	month = {2022 Dec},
	pages = {844-860},
	abstract = {Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: "(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)". A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1\% to 0.4\%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1\% to 0.4\% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment.},
	keywords = {Dry Eye Syndromes, Humans, Hyaluronic Acid, Lubricant Eye Drops, Tears},
	issn = {1755-3768},
	doi = {10.1111/aos.15159},
	author = {Hynnekleiv, Leif and Magno, Morten and Vernhardsdottir, Ragnheidur R and Moschowits, Emily and T{\o}nseth, Kim Alexander and Dartt, Darlene A. and Vehof, Jelle and Utheim, Tor P}
}
@article {1504080,
	title = {Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia},
	journal = {Nat Genet},
	volume = {52},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {401-407},
	abstract = {Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4\% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.},
	issn = {1546-1718},
	doi = {10.1038/s41588-020-0599-0},
	author = {Hysi, Pirro G and Choquet, H{\'e}l{\`e}ne and Khawaja, Anthony P and Wojciechowski, Robert and Tedja, Milly S and Yin, Jie and Simcoe, Mark J and Patasova, Karina and Mahroo, Omar A and Thai, Khanh K and Cumberland, Phillippa M and Melles, Ronald B and Verhoeven, Virginie J M and Vitart, Veronique and Segre, Ayellet and Stone, Richard A and Wareham, Nick and Hewitt, Alex W and Mackey, David A and Klaver, Caroline C W and Macgregor, Stuart and Consortium for Refractive Error and Myopia and Khaw, Peng T and Foster, Paul J and UK Eye and Vision Consortium and Guggenheim, Jeremy A and 23andMe Inc. and Rahi, Jugnoo S and Jorgenson, Eric and Hammond, Christopher J}
}
@article {303906,
	title = {Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.},
	journal = {Nat Genet},
	volume = {46},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {1126-30},
	abstract = {Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 {\texttimes} 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 {\texttimes} 10(-11) for rs2472493 near ABCA1 and P = 6.39 {\texttimes} 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 {\texttimes} 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.},
	issn = {1546-1718},
	doi = {10.1038/ng.3087},
	author = {Hysi, Pirro G and Cheng, Ching-Yu and Springelkamp, Henri{\"e}t and Macgregor, Stuart and Bailey, Jessica N Cooke and Wojciechowski, Robert and Vitart, Veronique and Nag, Abhishek and Hewitt, Alex W and H{\"o}hn, Ren{\'e} and Venturini, Cristina and Mirshahi, Alireza and Ramdas, Wishal D and Thorleifsson, Gudmar and Vithana, Eranga and Khor, Chiea-Chuen and Stefansson, Arni B and Liao, Jiemin and Haines, Jonathan L and Amin, Najaf and Wang, Ya Xing and Wild, Philipp S and Ozel, Ayse B and Li, Jun Z and Fleck, Brian W and Zeller, Tanja and Staffieri, Sandra E and Teo, Yik-Ying and Cuellar-Partida, Gabriel and Luo, Xiaoyan and Allingham, R Rand and Richards, Julia E and Senft, Andrea and Karssen, Lennart C and Zheng, Yingfeng and Bellenguez, C{\'e}line and Xu, Liang and Iglesias, Adriana I and Wilson, James F and Kang, Jae H and van Leeuwen, Elisabeth M and Jonsson, Vesteinn and Thorsteinsdottir, Unnur and Despriet, Dominiek D G and Ennis, Sarah and Moroi, Sayoko E and Martin, Nicholas G and Jansonius, Nomdo M and Yazar, Seyhan and Tai, E-Shyong and Amouyel, Philippe and Kirwan, James and van Koolwijk, Leonieke M E and Hauser, Michael A and Jonasson, Fridbert and Leo, Paul and Loomis, Stephanie J and Fogarty, Rhys and Rivadeneira, Fernando and Kearns, Lisa and Lackner, Karl J and de Jong, Paulus T V M and Simpson, Claire L and Pennell, Craig E and Oostra, Ben A and Uitterlinden, Andr{\'e} G and Saw, Seang-Mei and Lotery, Andrew J and Bailey-Wilson, Joan E and Hofman, Albert and Vingerling, Johannes R and Maubaret, C{\'e}cilia and Pfeiffer, Norbert and Wolfs, Roger C W and Lemij, Hans G and Young, Terri L and Pasquale, Louis R and Delcourt, C{\'e}cile and Spector, Timothy D and Klaver, Caroline C W and Small, Kerrin S and Burdon, Kathryn P and Stefansson, Kari and Wong, Tien-Yin and BMES GWAS Group and NEIGHBORHOOD Consortium and Wellcome Trust Case Control Consortium 2 and Viswanathan, Ananth and Mackey, David A and Craig, Jamie E and Wiggs, Janey L and van Duijn, Cornelia M and Hammond, Christopher J and Aung, Tin}
}
@article {669281,
	title = {PGC-1α Induces Human RPE Oxidative Metabolism and Antioxidant Capacity.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {3},
	year = {2016},
	month = {2016 Mar 1},
	pages = {1038-51},
	abstract = {PURPOSE: Oxidative stress and metabolic dysregulation of the RPE have been implicated in AMD; however, the molecular regulation of RPE metabolism remains unclear. The transcriptional coactivator, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) is a powerful mediator of mitochondrial function. This study examines the ability of PGC-1α to regulate RPE metabolic program and oxidative stress response. METHODS: Primary human fetal RPE (hfRPE) and ARPE-19 were matured in vitro using standard culture conditions. Mitochondrial mass of RPE was measured using MitoTracker staining and citrate synthase activity. Expression of PGC-1 isoforms, RPE-specific genes, oxidative metabolism proteins, and antioxidant enzymes was analyzed by quantitative PCR and Western blot. Mitochondrial respiration and fatty-acid oxidation were monitored using the Seahorse extracellular flux analyzer. Expression of PGC-1α was increased using adenoviral delivery. ARPE-19 were exposed to hydrogen peroxide to induce oxidative stress. Reactive oxygen species were measured by CM-H2DCFDA fluorescence. Cell death was analyzed by LDH release. RESULTS: Maturation of ARPE-19 and hfRPE was associated with significant increase in mitochondrial mass, expression of oxidative phosphorylation (OXPHOS) genes, and PGC-1α gene expression. Overexpression of PGC-1α increased expression of OXPHOS and fatty-acid β-oxidation genes, ultimately leading to the potent induction of mitochondrial respiration and fatty-acid oxidation. PGC-1α gain of function also strongly induced numerous antioxidant genes and, importantly, protected RPE from oxidant-mediated cell death without altering RPE functions. CONCLUSIONS: This study provides important insights into the metabolic changes associated with RPE functional maturation and identifies PGC-1α as a potent driver of RPE mitochondrial function and antioxidant capacity.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17758},
	author = {Iacovelli, Jared and Rowe, Glenn C and Khadka, Arogya and Diaz-Aguilar, Daniel and Spencer, Carrie and Arany, Zoltan and Saint-Geniez, Magali}
}
@article {931086,
	title = {Pharmacodynamic profile of mydriatic agents delivered by ocular piezo-ejection microdosing compared with conventional eyedropper.},
	journal = {Ther Deliv},
	year = {2016},
	month = {2016 Oct 13},
	abstract = {AIM: Eyedroppers deliver medication volumes exceeding conjunctival absorptive capacity, causing spillage and risking ocular/systemic complications. We evaluated piezoelectric microdosing. Results/methodology: Subjects (n = 102) received precision microdroplet delivery of phenylephrine (2.5\%) and tropicamide (1.0\%): 1 {\texttimes} 1.5 μl, 1 {\texttimes} 6 μl or 2 {\texttimes} 3 μl of each (randomized 1:1:1), into one eye. Contralateral eyes received eyedropper doses of both drugs. Outcomes were pupil dilation (0-60 min) and patient satisfaction. Six-microliter microdosing achieved comparable, and 2 {\texttimes} 3 μl met/exceeded dilation speed and magnitude versus eyedropper. Separately, participants preferred piezoelectric saline self-delivery to eyedroppers, reporting better head-positioning comfort, reduced tearing/overflow and increased likelihood of adhering to ocular medication regimens. CONCLUSION: Piezoelectric microdosing achieves comparable effects as eyedroppers delivering 4-17-fold larger doses. Microdosing may enhance patient adherence to ocular medication regimens while minimizing side effects.},
	issn = {2041-6008},
	doi = {10.4155/tde-2016-0061},
	author = {Ianchulev, Tsontcho and Chayet, Arturo and Kahook, Malik and Packer, Mark and Pasquale, Louis and Weinreb, Robert N}
}
@article {1573120,
	title = {Interspecies Correlations between Human and Mouse -Associated Recessive Disease},
	journal = {J Clin Med},
	volume = {10},
	number = {3},
	year = {2021},
	month = {2021 Jan 27},
	abstract = {-associated recessive disease in humans is historically defined by congenital night blinding retinopathy, characterized by an initial increase in short-wavelength (S)-cone sensitivity and progressive loss of rod and cone function. The retinal degeneration 7 () murine model, harboring a recessive mutation in the mouse ortholog of , has been a well-studied disease model and recently evaluated as a therapeutic model for -associated retinal degenerations. This study aims to draw parallels between human and mouse -related disease through examination of spectral domain optical coherence tomography (SD-OCT) imaging between different stage of human disease and its murine counterpart. We propose that SD-OCT is a useful non-invasive diagnostic tool to compare human clinical dystrophy presentation with that of the mouse and make inference that may be of therapeutically relevance. Additionally, a longitudinal assessment of disease progression, utilizing available clinical data from our patients as well as extensive retrospective analysis of visual acuity data from published cases of human -related disease, was curated to identify further valuable correlates between human and mouse disease. Results of this study validate the slow progression of -associated disease in humans and the mice and identify SD-OCT characteristics in patients at or near the vascular arcades that correlate well with the whorls and rosettes that are seen also in the mouse and point to imaging features that appear to be associated with better preserved S-cone mediated retinal function. The correlation of histological findings between mice and human imaging provides a solid foundation for diagnostic use of pathophysiological and prognostic information to further define characteristics and a relevant timeline for therapeutic intervention in the field of -associated retinopathies.},
	issn = {2077-0383},
	doi = {10.3390/jcm10030475},
	author = {Iannaccone, Alessandro and Brabbit, Emily and Lopez-Miro, Christiaan and Love, Zoe and Griffiths, Victoria and Kedrov, Marina and Haider, Neena B}
}
@article {1195271,
	title = {Electrophysiological Studies in Thyroid Associated Orbitopathy: A Systematic Review},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Sep 21},
	pages = {12108},
	abstract = {Dysthyroid optic neuropathy (DON) is the commonest cause of blindness in thyroid associated orbitopathy (TAO). While diagnosis remains clinical, objective tests for eyes with early or equivocal findings are lacking. Various electrophysiological studies (EPS) have been reported, yet the types and parameters useful for DON remain inconclusive. We performed a systematic literature search in MEDLINE, EMBASE and the Cochrane databases via the OVID platform up to August 20, 2017. 437 records were identified for screening and 16 original studies (1327 eyes, 787 patients) were eligible for review. Pattern visual evoked potential (pVEP) was the most frequently studied EPS. Eyes of TAO patients with DON showed delayed P100 latencies, decreased P100 amplitudes or delayed N75 latencies during pVEP, compared to those without or healthy controls. Due to study heterogeneity, no quantitative analysis was possible. This review highlights the most common type (pVEP) and useful parameters (P100 latency and amplitude) of EPS, and supports further research on them using standardized testing conditions.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-11998-0},
	author = {Iao, Tiara W U and Rong, Shi Song and Ling, An Ni and Brel{\'e}n, M{\r a}rten E and Young, Alvin Lerrmann and Chong, Kelvin K L}
}
@article {1078746,
	title = {Co-infecting microorganisms dramatically alter pathogen gene essentiality during polymicrobial infection},
	journal = {Nat Microbiol},
	volume = {2},
	year = {2017},
	month = {2017 May 30},
	pages = {17079},
	abstract = {Identifying genes required by pathogens during infection is critical for antimicrobial development. Here, we use a Monte Carlo simulation-based method to analyse high-throughput transposon sequencing data to determine the role of infection site and co-infecting microorganisms on the in vivo {\textquoteright}essential{\textquoteright} genome of Staphylococcus aureus. We discovered that co-infection of murine surgical wounds with Pseudomonas aeruginosa results in conversion of \~{}25\% of the in vivo S. aureus mono-culture essential genes to non-essential. Furthermore, 182 S. aureus genes are uniquely essential during co-infection. These {\textquoteright}community dependent essential{\textquoteright} (CoDE) genes illustrate the importance of studying pathogen gene essentiality in polymicrobial communities.},
	issn = {2058-5276},
	doi = {10.1038/nmicrobiol.2017.79},
	author = {Ibberson, Carolyn B and Stacy, Apollo and Fleming, Derek and Dees, Justine L and Rumbaugh, Kendra and Gilmore, Michael S and Whiteley, Marvin}
}
@article {1359932,
	title = {A Controlled Impact of Optic Nerve as a New Model of Traumatic Optic Neuropathy in Mouse},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {13},
	year = {2018},
	month = {2018 Nov 01},
	pages = {5548-5557},
	abstract = {Purpose: Traumatic optic neuropathy (TON) is the most feared visual consequence of head and ocular trauma in both military and civilian communities, for which standard treatment does not exist. Animal models are critical for the development of novel TON therapies as well as the understanding of TON pathophysiology. However, the models currently used for TON have some limitations regarding consistency and mirroring the exact pathological progression of TON in closed ocular trauma. In this study, we modified the model of controlled cortical impact and adapted it for studying TON. Methods: We defined new standardized procedures to induce TON in mice, wherein the optic nerve is reproducibly exposed to a graded controlled impact of known velocity to produce a graded deficit in retinal ganglion cell (RGC) electrophysiological functions. Results: The key results of validating this newly modified model, "controlled orbital impact (COI)," included (1) the injury parameters (velocity as well as contusion depth and time), which were quantifiable and manageable to generate a wide range of TON severities; (2) a reproducible endpoint of diminished positive scotopic threshold response (pSTR) has been achieved without the interference of surgical variability and destruction of surrounding tissues; (3) the contralateral eyes showed no significant difference to the eyes of na{\"\i}ve mice, allowing them to be used as an internal control to minimize interindividual variability among mice; and (4) the occurrence of injury-associated mortality and/or ocular comorbidity was rare. Conclusions: Taken together, this model overcomes some limitations of prior TON mouse models and provides an innovative platform to identify therapeutic targets for neuroprotection and/or neurorestoration following traumatic ocular injury.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-24773},
	author = {Ibrahim, Ahmed S and Elmasry, Khaled and Wan, Ming and Abdulmoneim, Samer and Still, Amber and Khan, Farid and Khalil, Abraham and Saul, Alan and Hoda, Md Nasrul and Al-Shabrawey, Mohamed}
}
@article {1522711,
	title = {Bone Morphogenetic Protein (BMP)4 But Not BMP2 Disrupts the Barrier Integrity of Retinal Pigment Epithelia and Induces Their Migration: A Potential Role in Neovascular Age-Related Macular Degeneration},
	journal = {J Clin Med},
	volume = {9},
	number = {7},
	year = {2020},
	month = {2020 Jul 19},
	abstract = {Disruption of retinal pigment epithelial (RPE) barrier integrity and RPE migration are hallmark features in neovascular age-related macular degeneration (nAMD), but the underlying causes and pathophysiology are not completely well-defined. Herein, we aimed to evaluate the effect of bone morphogenetic proteins (BMPs) on the barrier function and migration of RPE. In particular, we investigated the role of BMP2 and BMP4 in these processes as our analysis of RNA-sequencing (seq) data from human donor eyes demonstrated that they are highly differentially expressed BMP members in macular RPE/choroid versus macular retina. We used electrical cell-substrate impedance sensing (ECIS) system to monitor precisely in real time the barrier integrity and migration of ARPE-19 after treatment with various concentrations of BMP2 or BMP4. Immunofluorescence was also used to assess the changes in the expression and the organization of the key tight junction protein, zona occludens (ZO)-1, in ARPE-19 cells under BMP2 or BMP4 treatment. This was followed by measuring the activity of matrix metalloproteinases (MMPs). Finally, RNA-seq and ELISA were used to determine the local and circulating levels of BMP2 and BMP4 in retinas and serum samples from nAMD donors. Our ECIS results showed that BMP4 but not BMP2 decreased the transcellular electrical resistance (TER) of ARPE-19 and increased their migration in comparison with control (vehicle-treated cells). Furthermore, immunofluorescence showed a disorganization of ZO-1 in BMP4-treated ARPE-19 not in BMP2-treated cells or vehicle-treated controls. This effect of BMP4 was associated with significant increases in the activity of MMPs, specifically MMP2. Lastly, these results were corroborated by additional findings that circulating but not local BMP4 levels were significantly higher in nAMD donor samples compared to controls. Collectively, our results demonstrated unreported effects of BMP4 on inducing RPE dysfunction and suggest that BMP4 but not BMP2 may represent a potential therapeutic target in nAMD.},
	issn = {2077-0383},
	doi = {10.3390/jcm9072293},
	author = {Ibrahim, Ahmed S and Hussein, Khaled and Wang, Fang and Wan, Ming and Saad, Nancy and Essa, Maamon and Kim, Ivana and Shakoor, Akbar and Owen, Leah A and Deangelis, Margaret M and Al-Shabrawey, Mohamed}
}
@article {1677656,
	title = {Ocular manifestations of COVID-19 in pediatric patients},
	journal = {Ther Adv Ophthalmol},
	volume = {15},
	year = {2023},
	month = {2023 Jan-Dec},
	pages = {25158414221149916},
	abstract = {The coronavirus disease-19 (COVID-19) infection may remain asymptomatic or may have several different presentations. Although this disease primarily affects the respiratory system, systemic manifestations affecting the gastrointestinal, cardiovascular, neurological, otorhinolaryngologic, and ophthalmic systems have been reported. Ophthalmic signs may be the first and only sign of COVID-19 infection in children. In the current narrative review, we report the ophthalmic manifestations of COVID-19 in the pediatric age cohort. We performed a comprehensive literature search for the publications on ophthalmic manifestations of COVID-19 in children between 1 March 2020 and 1 January 2022 and compiled the ophthalmic manifestations of this entity among the pediatric population. Conjunctivitis is the most common ophthalmic manifestation in children and can develop at any stage of the disease. Ophthalmic manifestations are seen more commonly in children with severe systemic disease. Long-term and indirect consequence of the COVID-19 disease is the rise of myopia among children. Ophthalmic signs may be the first and only sign of COVID-19 infection in children. Pediatricians, as well as ophthalmologists, must keep observing all children with COVID-19 closely for ophthalmic signs.},
	issn = {2515-8414},
	doi = {10.1177/25158414221149916},
	author = {Ichhpujani, Parul and Singh, Rohan Bir and Dhillon, Hennaav Kaur and Kumar, Suresh}
}
@article {1319468,
	title = {Juvenile Open Angle Glaucoma With Nonbullous Congenital Ichthyosiform Erythroderma},
	journal = {J Glaucoma},
	volume = {27},
	number = {11},
	year = {2018},
	month = {2018 Nov},
	pages = {e180-e182},
	abstract = {INTRODUCTION: Glaucoma in patients with nonbullous congenital ichthyosiform erythroderma (NBCIE) is a rare entity that has not been described in a histologically confirmed case. We present a unique case of coexisting glaucoma, ichthyosis, and dwarfism that has not been previously described. METHODS: We present a case of NBCIE with glaucoma and dwarfism that presented to our outpatient department. The patient was referred for watering and photophobia that were due to an epithelial defect that was subsequently managed conservatively. Investigations revealed the existence of a constellation of findings that are presented here. RESULTS: NBCIE, glaucoma, and dwarfism represent a spectrum of diseases that seem to have a syndromic association. More gene linkage-based analysis are, however, needed to further confirm our observations. CONCLUSIONS: NBCIE, glaucoma, and dwarfism can often occur together and need to be assessed and managed individually. Early diagnosis of this spectrum can help improve patient management and quality of life. Dermatologists must get an ocular examination conducted for icthyoses patients.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001016},
	author = {Ichhpujani, Parul and Thakur, Sahil and Kumar, Suresh and Singh, Rohan B}
}
@article {1430529,
	title = {Visual implications of digital device usage in school children: a cross-sectional study},
	journal = {BMC Ophthalmol},
	volume = {19},
	number = {1},
	year = {2019},
	month = {2019 Mar 12},
	pages = {76},
	abstract = {PURPOSE: To evaluate the use of digital devices, reading habits and the prevalence of eyestrain among urban Indian school children, aged 11-17 years. METHODS: The study included 576 adolescents attending urban schools who were surveyed regarding their electronic device usage. Additional information on the factors that may have an effect on ocular symptoms was collected. RESULTS: Twenty percent of students aged 11 in the study population use digital devices on a daily basis, in comparison with 50\% of students aged 17. In addition to using these devices as homework aids, one third of study participants reported using digital devices for reading instead of conventional textbooks. The majority of students preferred sitting on a chair while reading (77\%; 445 students), with only 21\% (123 students) preferring to lie on the bed and 8 students alternating between chair and bed. There was a significant association between the students who preferred to lie down and those who experienced eyestrain, as reported by a little over one fourth of the student population (27\%). Out of 576 students, 18\% (103) experienced eyestrain at the end of the day after working on digital devices. CONCLUSIONS: The increased use of digital devices by adolescents brings a new challenge of digital eyestrain at an early age. Our study reports the patterns of electronic device usage by school children, evaluates factors associated with eyestrain and highlights the need for further investigation of these issues.},
	issn = {1471-2415},
	doi = {10.1186/s12886-019-1082-5},
	author = {Ichhpujani, Parul and Singh, Rohan Bir and Foulsham, William and Thakur, Sahil and Lamba, Amtoj Singh}
}
@article {1658676,
	title = {Analysing the change in contrast sensitivity post-travoprost treatment in primary open-angle glaucoma patients using Spaeth Richman contrast sensitivity test},
	journal = {Int Ophthalmol},
	volume = {43},
	number = {6},
	year = {2023},
	month = {2023 Jun},
	pages = {2037-2047},
	abstract = {OBJECTIVE: To determine the ability of the Internet-based Spaeth/Richman Contrast Sensitivity (SPARCS) in assessing the change in contrast sensitivity (both central and peripheral) post-treatment with travoprost 0.004\%. DESIGN: This is a prospective observational study. METHODS AND PARTICIPANTS: Data of 62 eyes (33 patients) undergoing treatment for na{\"\i}ve POAG patients were analysed. Patients were followed up for a period of six months after starting topical travoprost (Travatan 0.004\%, Alcon), and the change in central and peripheral CS was studied. RESULTS: Mean total SPARCS score at baseline was 69 {\textpm} 10.99, improved to 74.62 {\textpm} 9.50 after 6\&nbsp;months of therapy (p: 0.001) in all the glaucoma severity groups. Mean SPARCS score at baseline in mild glaucoma group was 72.05 {\textpm} 9.87, in the moderate glaucoma group, it was 62.23 {\textpm} 9.2, and in the severe glaucoma group, it was 59.36 {\textpm} 11.65. After 6\&nbsp;months of treatment with travoprost, the CS improved to 76.05 {\textpm} 8.36 in mild group, 76.69 {\textpm} 8.82 in moderate group and 67.18 {\textpm} 11.15 in severe group (p value: 0.014). The percentage change in the CS from baseline showed significant improvement in the superotemporal quadrant at 1\&nbsp;month (p value: 0.032), superonasal quadrant (p value: 0.049), inferotemporal quadrant at 3\&nbsp;months (p value: 0.003) and 6\&nbsp;months (p value: 0.039). Inferonasal quadrant was affected most by glaucoma. A statistically significant correlation was seen between total SPARCS score with MD and PSD. Correlation was also seen between the percentage change in CS and average RNFL thickness at 3 and 6\&nbsp;months. CONCLUSION: Both central and peripheral CS improve following IOP reduction with travoprost. Change in the CS has a significant correlation with RNFL thickness and the perimetric indices.},
	keywords = {Antihypertensive Agents, Contrast Sensitivity, Glaucoma, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Travoprost, Vision Tests},
	issn = {1573-2630},
	doi = {10.1007/s10792-022-02603-z},
	author = {Ichhpujani, Parul and Rodrigues, Ann Maria and Kumar, Suresh and Singh, Rohan Bir}
}
@article {1635621,
	title = {Effect of laser peripheral iridotomy on contrast sensitivity using Spaeth/Richman Contrast Sensitivity test},
	journal = {Ther Adv Ophthalmol},
	volume = {14},
	year = {2022},
	month = {2022 Jan-Dec},
	pages = {25158414221078142},
	abstract = {Background: Laser peripheral iridotomy (LPI) is the current standard of care for primary angle-closure glaucoma. The existing literature lacks evidence regarding the effects of LPI on contrast sensitivity (CS) after the procedure. Objective: This study evaluates central and peripheral CS in patients undergoing LPI using the computer-based, Spaeth/Richman Contrast Sensitivity (SPARCS) test. Methods: We performed a pilot, prospective, interventional cohort study including 30 patients of primary angle-closure suspect (PACS) or primary angle closure (PAC) in both eyes. LPI was performed after a detailed history and clinical examination using standard procedure in all eyes. Intraocular pressure (IOP) and CS testing using SPARCS was performed before, 2 weeks and 3 months after LPI. Results: Data analyses revealed female predominance (66.67\%, 20/30); the mean age of enrolled patients was 49.93 {\textpm} 10.43 years, and presenting acuity was 0.02 {\textpm} 0.06 (Log of Minimum Angle of Resolution [LogMAR]). The mean vertical cup-to-disc ratio (VCDR), mean deviation (MD in dB) and pattern standard deviation (PSD in dB) were 0.34 {\textpm} 0.09, -2.36 {\textpm} 1.72 and 2.34 {\textpm} 0.81, respectively. There was a statistically significant decrease between the pre- (15.17 {\textpm} 3.83 mmHg) and 2 weeks post-LPI (11.70 {\textpm} 1.53 mmHg) IOP (p \&lt; 0.001). However, CS in the pre- (73.47 {\textpm} 9.88) and 3 months post-LPI (75.20 {\textpm} 11.98) SPARCS scores did not reveal any statistical difference. The group-wise analysis showed a similar trend between PAC and PACS patients. Conclusion: LPI does not affect central as well as peripheral CS assessment in patients with the primary angle-closure disease.},
	issn = {2515-8414},
	doi = {10.1177/25158414221078142},
	author = {Ichhpujani, Parul and Thakur, Sahil and Singh, Tanu and Singh, Rohan Bir and Kumar, Suresh}
}
@article {1318863,
	title = {Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases},
	journal = {Nat Commun},
	volume = {9},
	number = {1},
	year = {2018},
	month = {2018 May 14},
	pages = {1864},
	abstract = {Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, \&gt;20\% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 {\texttimes} 10) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-03646-6},
	author = {Iglesias, Adriana I and Mishra, Aniket and Vitart, Veronique and Bykhovskaya, Yelena and H{\"o}hn, Ren{\'e} and Springelkamp, Henri{\"e}t and Cuellar-Partida, Gabriel and Gharahkhani, Puya and Bailey, Jessica N Cooke and Willoughby, Colin E and Li, Xiaohui and Yazar, Seyhan and Nag, Abhishek and Khawaja, Anthony P and Pola{\v s}ek, Ozren and Siscovick, David and Mitchell, Paul and Tham, Yih Chung and Haines, Jonathan L and Kearns, Lisa S and Hayward, Caroline and Yuan Shi and van Leeuwen, Elisabeth M and Taylor, Kent D and Blue Mountains Eye Study{\textemdash}GWAS group and Bonnemaijer, Pieter and Rotter, Jerome I and Martin, Nicholas G and Zeller, Tanja and Mills, Richard A and Staffieri, Sandra E and Jonas, Jost B and Schmidtmann, Irene and Boutin, Thibaud and Kang, Jae H and Lucas, Sionne E M and Wong, Tien Yin and Beutel, Manfred E and Wilson, James F and NEIGHBORHOOD Consortium and Wellcome Trust Case Control Consortium 2 (WTCCC2) and Uitterlinden, Andr{\'e} G and Vithana, Eranga N and Foster, Paul J and Hysi, Pirro G and Hewitt, Alex W and Khor, Chiea Chuen and Pasquale, Louis R and Montgomery, Grant W and Klaver, Caroline C W and Aung, Tin and Pfeiffer, Norbert and Mackey, David A and Hammond, Christopher J and Cheng, Ching-Yu and Craig, Jamie E and Rabinowitz, Yaron S and Wiggs, Janey L and Burdon, Kathryn P and van Duijn, Cornelia M and Macgregor, Stuart}
}
@article {1417563,
	title = {Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases},
	journal = {Nat Commun},
	volume = {10},
	number = {1},
	year = {2019},
	month = {2019 01 08},
	pages = {155},
	abstract = {Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.},
	issn = {2041-1723},
	doi = {10.1038/s41467-018-07819-1},
	author = {Iglesias, Adriana I and Mishra, Aniket and Vitart, Veronique and Bykhovskaya, Yelena and H{\"o}hn, Ren{\'e} and Springelkamp, Henri{\"e}t and Cuellar-Partida, Gabriel and Gharahkhani, Puya and Bailey, Jessica N Cooke and Willoughby, Colin E and Li, Xiaohui and Yazar, Seyhan and Nag, Abhishek and Khawaja, Anthony P and Pola{\v s}ek, Ozren and Siscovick, David and Mitchell, Paul and Tham, Yih Chung and Haines, Jonathan L and Kearns, Lisa S and Hayward, Caroline and Yuan Shi and van Leeuwen, Elisabeth M and Taylor, Kent D and Blue Mountains Eye Study-GWAS group and Bonnemaijer, Pieter and Rotter, Jerome I and Martin, Nicholas G and Zeller, Tanja and Mills, Richard A and Souzeau, Emmanuelle and Staffieri, Sandra E and Jonas, Jost B and Schmidtmann, Irene and Boutin, Thibaud and Kang, Jae H and Lucas, Sionne E M and Wong, Tien Yin and Beutel, Manfred E and Wilson, James F and Wellcome Trust Case Control Consortium 2 (WTCCC2) and NEIGHBORHOOD Consortium and Uitterlinden, Andr{\'e} G and Vithana, Eranga N and Foster, Paul J and Hysi, Pirro G and Hewitt, Alex W and Khor, Chiea Chuen and Pasquale, Louis R and Montgomery, Grant W and Klaver, Caroline C W and Aung, Tin and Pfeiffer, Norbert and Mackey, David A and Hammond, Christopher J and Cheng, Ching-Yu and Craig, Jamie E and Rabinowitz, Yaron S and Wiggs, Janey L and Burdon, Kathryn P and van Duijn, Cornelia M and Macgregor, Stuart}
}
@article {836866,
	title = {Quality Control for the Illumina HumanExome BeadChip.},
	journal = {Curr Protoc Hum Genet},
	volume = {90},
	year = {2016},
	month = {2016},
	pages = {2.14.1-2.14.16},
	abstract = {The Illumina HumanExome BeadChip and other exome-based genotyping arrays offer inexpensive genotyping of some 240,000 mostly nonsynonymous coding variants across the human genome. The HumanExome chip, with its highly non-uniform distribution of markers and emphasis on rare coding variants, presents some unique challenges for quality control (QC) and data cleaning. Here, we describe QC procedures for HumanExome data, with examples of challenges specific to exome arrays from our experience cleaning a data set of \~{}7,500 samples from the NEIGHBORHOOD Consortium. We focus on standard procedures for QC of genome-wide array data including genotype calling, sex verification, sample identity verification, relationship checking, and population structure that are complicated by the HumanExome panel{\textquoteright}s enrichment in rare, exonic variation. {\textcopyright} 2016 by John Wiley \&amp; Sons, Inc.},
	issn = {1934-8258},
	doi = {10.1002/cphg.15},
	author = {Igo, Robert P and Cooke Bailey, Jessica N and Romm, Jane and Haines, Jonathan L and Wiggs, Janey L}
}
@article {1323930,
	title = {Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector},
	journal = {J Am Soc Nephrol},
	volume = {29},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {2287-2297},
	abstract = {BACKGROUND: After injury, mesenchymal progenitors in the kidney interstitium differentiate into myofibroblasts, cells that have a critical role in kidney fibrogenesis. The ability to deliver genetic material to myofibroblast progenitors could allow new therapeutic approaches to treat kidney fibrosis. Preclinical and clinical studies show that adeno-associated viruses (AAVs) efficiently and safely transduce various tissue targets ; however, protocols for transduction of kidney mesenchymal cells have not been established. METHODS: We evaluated the transduction profiles of various pseudotyped AAV vectors expressing either GFP or Cre recombinase reporters in mouse kidney and human kidney organoids. RESULTS: Of the six AAVs tested, a synthetic AAV called Anc80 showed specific and high-efficiency transduction of kidney stroma and mesangial cells. We characterized the cell specificity, dose dependence, and expression kinetics and showed the efficacy of this approach by knocking out Gli2 from kidney mesenchymal cells by injection of Anc80-Cre virus into either homozygous or heterozygous Gli2-floxed mice. After unilateral ureteral obstruction, the homozygous Gli2-floxed mice had less fibrosis than the Gli2 heterozygotes had. We observed the same antifibrotic effect in -catenin-floxed mice injected with Anc80-Cre virus before obstructive injury, strongly supporting a central role for canonical Wnt signaling in kidney myofibroblast activation. Finally, we showed that the Anc80 synthetic virus can transduce the mesenchymal lineage in human kidney organoids. CONCLUSIONS: These studies establish a novel method for inducible knockout of floxed genes in mouse mesangium, pericytes, and perivascular fibroblasts and are the foundation for future gene therapy approaches to treat kidney fibrosis.},
	issn = {1533-3450},
	doi = {10.1681/ASN.2018040426},
	author = {Ikeda, Yoichiro and Sun, Zhao and Ru, Xiao and Vandenberghe, Luk H and Humphreys, Benjamin D}
}
@article {655061,
	title = {Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type.},
	journal = {J Neural Eng},
	volume = {13},
	number = {2},
	year = {2016},
	month = {2016 Feb 23},
	pages = {025002},
	abstract = {OBJECTIVE: To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. APPROACH: We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000 ms). Each stimulus was a 4 ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. MAIN RESULTS: ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported {\textquoteright}reset{\textquoteright} behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7 Hz) that maximized the ratio of the responses arising in ON versus OFF cells. SIGNIFICANCE: Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (\&gt;\&nbsp;\~{}7 Hz) due to the reset while responses of OFF cells are strong at low rates (\&lt;\&nbsp;\~{}4 Hz) due to reduced desensitization, both reducing the ratio of ON to OFF responses. In combination with previous results indicating that responses in ON cells more closely match physiological patterns (Im and Fried 2015 J. Physiol. 593 3577-96), our results offer a potential reason for the user preference of intermediate rates (5-7 Hz).},
	issn = {1741-2552},
	doi = {10.1088/1741-2560/13/2/025002},
	author = {Im, Maesoon and Fried, Shelley I}
}
@article {1580499,
	title = {Genome-wide association studies identify two novel loci conferring susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes},
	journal = {Hum Mol Genet},
	volume = {30},
	number = {8},
	year = {2021},
	month = {2021 May 17},
	pages = {716-726},
	abstract = {Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (P \&lt; 1.0 {\texttimes} 10-4) in an independent case-control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stages 1 and 2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, P = 1.62 {\texttimes} 10-9, odds ratio (OR) = 1.17, 95\% confidence interval (CI) 1.11-1.23, and rs140508424 within PALM2 on chromosome 9, P = 4.19 {\texttimes} 10-8, OR = 1.61, 95\% CI 1.36-1.91. However, the association of these two loci was not replicated in Korean, European or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (P = 2.17 {\texttimes} 10-6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddab044},
	author = {Imamura, Minako and Takahashi, Atsushi and Matsunami, Masatoshi and Horikoshi, Momoko and Iwata, Minoru and Araki, Shin-Ichi and Toyoda, Masao and Susarla, Gayatri and Ahn, Jeeyun and Park, Kyu Hyung and Kong, Jinhwa and Moon, Sanghoon and Sobrin, Lucia and International Diabetic Retinopathy and Genetics CONsortium (iDRAGON) and Yamauchi, Toshimasa and Tobe, Kazuyuki and Maegawa, Hiroshi and Kadowaki, Takashi and Maeda, Shiro}
}
@article {1263346,
	title = {Postoperative Refractive Errors Following Pediatric Cataract Extraction with Intraocular Lens Implantation},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 13},
	pages = {1-8},
	abstract = {PURPOSE: Advances in surgical techniques allow implantation of intraocular lenses (IOL) with cataract extraction, even in young children. However, there are several challenges unique to the pediatric population that result in greater degrees of postoperative refractive error compared to adults. METHODS: Literature review of the techniques and outcomes of pediatric cataract surgery with IOL implantation. RESULTS: Pediatric cataract surgery is associated with several sources of postoperative refractive error. These include planned refractive error based on age or fellow eye status, loss of accommodation, and unexpected refractive errors due to inaccuracies in biometry technique, use of IOL power formulas based on adult normative values, and late refractive changes due to unpredictable eye growth. CONCLUSIONS: Several factors can preclude the achievement of optimal refractive status following pediatric cataract extraction with IOL implantation. There is a need for new technology to reduce postoperative refractive surprises and address refractive adjustment in a growing eye.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353812},
	author = {Indaram, Maanasa and VanderVeen, Deborah K}
}
@article {1137886,
	title = {Exudative Vitreoretinopathy in Dyskeratosis Congenita},
	journal = {Ophthalmology},
	volume = {124},
	number = {8},
	year = {2017},
	month = {2017 Aug},
	pages = {1246},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.01.044},
	author = {Indaram, Maanasa and Agarwal, Suneet and Yonekawa, Yoshihiro}
}
@article {1466912,
	title = {Advances in the diagnosis of giant cell arteritis},
	journal = {Curr Opin Ophthalmol},
	volume = {30},
	number = {6},
	year = {2019},
	month = {2019 Nov},
	pages = {407-411},
	abstract = {PURPOSE OF REVIEW: To summarize recent advances in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Less common manifestations of GCA include corneal edema, proptosis from lacrimal gland ischemia and sensorineuronal hearing loss. Histology studies have suggested that temporal artery biopsies (TAB) with fixed specimen lengths of 15 mm may be adequate to prevent false negative biopsies. In centers with appropriate radiologic expertise, a European rheumatology consensus guideline has proposed Doppler ultrasound as a first-line confirmatory test for GCA in lieu of temporal artery biopsy. Finding extracranial large vessel disease can help to diagnose GCA. Statistical prediction rules can help risk stratify patients with suspected GCA. Age and platelet level when maintained as continuous variables are the strongest predictors for GCA. SUMMARY: GCA can present with diverse ophthalmic and systemic presentations and expedient recognition of same can avoid diagnostic delay and possible vision loss, among other complications. TAB remains the conventional diagnostic standard test for GCA. The use of statistical prediction models and increased expertise in noninvasive imaging techniques such as ultrasound may decrease reliance on TAB, especially in patients determined to be at low risk for GCA.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000616},
	author = {Ing, Edsel and Pagnoux, Christian and Torun, Nurhan}
}
@article {1466920,
	title = {Diplopia and Giant Cell Arteritis},
	journal = {J Neuroophthalmol},
	volume = {39},
	number = {4},
	year = {2019},
	month = {2019 Dec},
	pages = {546-547},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000847},
	author = {Ing, Edsel B and Miller, Neil R and Ten Hove, Martin and Torun, Nurhan}
}
@article {1439850,
	title = {Comments on the giant cell arteritis probability score},
	journal = {Clin Exp Rheumatol},
	year = {2019},
	month = {2019 May 08},
	issn = {0392-856X},
	author = {Ing, Edsel and Sambhi, Gagan and Torun, Nurhan and Pagnoux, Christian}
}
@article {1424804,
	title = {Systematic Review of the Yield of Temporal Artery Biopsy for Suspected Giant Cell Arteritis},
	journal = {Neuroophthalmology},
	volume = {43},
	number = {1},
	year = {2019},
	month = {2019 Feb},
	pages = {18-25},
	abstract = {PURPOSE: To determine the positive yield (utility rate) of temporal artery biopsy (TAB) in patients with suspected giant cell arteritis (GCA). STUDY DESIGN: Systematic review (CRD42017078508) and meta-regression. MATERIALS AND METHODS: All articles concerning TAB for suspected GCA with English language abstracts from 1998 to 2017 were retrieved. Articles were excluded if they exclusively reported positive TAB, or only cases of known GCA. Where available, the pre-specified predictors of age, sex, vision symptoms, jaw claudication, duration of steroid treatment prior to TAB, specimen length, bilateral TAB, and use of ultrasound/MRI (imaging) were recorded for meta-regression. RESULTS: One hundred and thirteen articles met eligibility criteria. The was 92\%, and with such high heterogeneity, meta-analysis is unsuitable. The median yield of TAB was 0.25 (95\% confidence interval 0.21 to 0.27), with interquartile range 0.17 to 0.34. On univariate meta-regression age (coefficient 0.012, \&nbsp;=\&nbsp;0.025) was the only statistically significant patient factor associated with TAB yield. CONCLUSIONS: Systematic review revealed high heterogeneity in the yield of TAB. The median utility rate of 25\% and its interquartile range provides a benchmark for decisions regarding the under/overutilization of TAB and aids in the evaluation of non-invasive alternatives for the investigation of GCA.},
	issn = {0165-8107},
	doi = {10.1080/01658107.2018.1474372},
	author = {Ing, Edsel B and Wang, Dan Ni and Kirubarajan, Abirami and Benard-Seguin, Etienne and Ma, Jingyi and Farmer, James P and Belliveau, Michel J and Sholohov, Galina and Torun, Nurhan}
}
@article {1319469,
	title = {Lower ocular pulse amplitude with dynamic contour tonometry is associated with biopsy-proven giant cell arteritis},
	journal = {Can J Ophthalmol},
	volume = {53},
	number = {3},
	year = {2018},
	month = {2018 Jun},
	pages = {215-221},
	abstract = {OBJECTIVES: To determine the role of the ocular pulse amplitude (OPA) from Pascal dynamic contour tonometry in predicting the temporal artery biopsy (TABx) result in patients with suspected giant cell arteritis (GCA). DESIGN: Prospective validation study. PARTICIPANTS: Adults aged 50 years or older who underwent TABx from March 2015 to April 2017. METHODS: Subjects on high-dose glucocorticoids more than 14 days or without serology before glucocorticoid initiation were excluded. The OPA from both eyes was obtained and averaged just before TABx of the predominantly symptomatic side. The variables chosen for the a priori prediction model were age, average OPA, and C-reactive protein (CRP). Erythrocyte sedimentation rate (ESR), platelets, jaw claudication, and eye findings were also recorded. In this study, subjects with a negative biopsy were considered not to have GCA, and contralateral biopsy was performed if the clinical suspicion for GCA remained high. An external validation set (XVAL) was obtained. RESULTS: Of 109 TABx, 19 were positive and 90 were negative. On univariate logistic regression, the average OPA had 0.60 odds for positive TABx (p = 0.03), with no statistically significant difference in age, sex, CRP, ESR, or jaw claudication. In suspected GCA, an OPA of 1 mm Hg had positive likelihood ratio 4.74 and negative likelihood ratio 0.87 for positive TABx. Multivariate regression of the prediction model using optimal mathematical transforms (inverse OPA, log CRP, age \&gt;65 years) had area under the receiver operating characteristic curve (AUROC) = 0.85 and AUROC = 0.81. CONCLUSIONS: OPA is lower in subjects with biopsy-proven GCA and is a statistically significant predictor of GCA.},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2017.10.027},
	author = {Ing, Edsel and Pagnoux, Christian and Tyndel, Felix and Sundaram, Arun and Hershenfeld, Seymour and Ranalli, Paul and Chow, Shirley and Le, Tran and Lutchman, Carla and Rutherford, Susan and Lam, Kay and Bedi, Harleen and Torun, Nurhan}
}
@article {1511471,
	title = {Physician deaths from corona virus (COVID-19) disease},
	journal = {Occup Med (Lond)},
	volume = {70},
	number = {5},
	year = {2020},
	month = {2020 07 17},
	pages = {370-374},
	abstract = {BACKGROUND: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. AIMS: We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHODS: On 15 April 2020, a Google internet search was performed using the keywords {\textquoteright}doctor{\textquoteright}, {\textquoteright}physician{\textquoteright}, {\textquoteright}death{\textquoteright}, {\textquoteright}COVID{\textquoteright} and {\textquoteright}coronavirus{\textquoteright} in English and Farsi, and Chinese using the Baidu search engine. The age, sex and medical speciality of physicians who died from COVID-19 in the line of duty were recorded. Individuals greater than 90 years of age were excluded. RESULTS: We found 278 physicians who died with COVID-19 infection, but complete details were missing for 108 individuals. The average age of the physicians was 63.7 years with a median age of 66 years, and 90\% were male (235/261). General practitioners and emergency room doctors (108/254), respirologists (5/254), internal medicine specialists (13/254) and anaesthesiologists (6/254) comprised 52\% of those dying. Two per cent of the deceased were epidemiologists (5/254), 2\% were infectious disease specialists (4/254), 6\% were dentists (16/254), 4\% were ENT (9/254) and 3\% were ophthalmologists (8/254). The countries with the most reported physician deaths were Italy (121/278; 44\%), Iran (43/278; 15\%), Philippines (21/278; 8\%), Indonesia (17/278; 6\%), China (16/278; 6\%), Spain (12/278; 4\%), USA (12/278; 4\%) and UK (11/278;4\%). CONCLUSIONS: Physicians from all specialities may die from COVID. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.},
	keywords = {Adult, Aged, Betacoronavirus, Coronavirus Infections, Female, Humans, Male, Middle Aged, Pandemics, Physicians, Pneumonia, Viral},
	issn = {1471-8405},
	doi = {10.1093/occmed/kqaa088},
	author = {Ing, E B and Xu, Q A and Salimi, A and Torun, N}
}
@article {987971,
	title = {Kinetics of Angiogenic Responses in Corneal Transplantation},
	journal = {Cornea},
	volume = {36},
	number = {4},
	year = {2017},
	month = {2017 Apr},
	pages = {491-496},
	abstract = {PURPOSE: To delineate and compare the kinetics of corneal angiogenesis after high-risk (HR) versus low-risk (LR) corneal transplantation. METHODS: In mice, intrastromal sutures were placed in the recipient graft bed 2 weeks before allogeneic transplantation to induce angiogenesis and amplify the risk of graft rejection. Control (LR) graft recipients did not undergo suture placement, and thus the host bed remained avascular at the time of transplantation. Graft hemangiogenesis and opacity scores were evaluated for 8 weeks by slit-lamp biomicroscopy. Immunohistochemistry was used to measure CD31 (blood vessels) and LYVE-1 (lymphatic vessels) cells. RESULTS: Biphasic kinetics were observed for hemangiogenesis in both HR and LR transplant recipients using clinical and immunohistochemical assessments. The biphasic kinetics were composed of a rise-fall (phase 1) followed by a second rise (phase 2) in the degree of vessels. Compared with LR recipients, HR recipients showed higher hemangiogenesis (whole cornea and graft) throughout 8 weeks. Analyzing grafts revealed sustained presence of lymphatic vessels in HR recipients; however, lymphatic neovessels regressed in LR recipients 2 weeks posttransplantation. In contrast to HR host beds, the LR host bed microenvironment cannot sustain the growth of lymphatic neovessels in allografts, whereas it can sustain continued hemangiogenesis. CONCLUSIONS: The sustained presence of lymphatic vessels in HR host beds can facilitate host immunity against allografts and is likely associated with ongoing higher risk of rejection of these grafts in the long term, suggesting that therapeutic interventions targeting inflammation and lymphatic vessels need to be sustained long term in the HR corneal transplant setting.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001127},
	author = {Inomata, Takenori and Mashaghi, Alireza and Di Zazzo, Antonio and Lee, Sang-Mok and Chiang, Homer and Dana, Reza}
}
@article {1474186,
	title = {Characteristics and Risk Factors Associated With Diagnosed and Undiagnosed Symptomatic Dry Eye Using a Smartphone Application},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Nov 27},
	abstract = {Importance: The incidence of dry eye disease has increased; the potential for crowdsource data to help identify undiagnosed dry eye in symptomatic individuals remains unknown. Objective: To assess the characteristics and risk factors associated with diagnosed and undiagnosed symptomatic dry eye using the smartphone app DryEyeRhythm. Design, Setting, and Participants: A cross-sectional study using crowdsourced data was conducted including individuals in Japan who downloaded DryEyeRhythm and completed the entire questionnaire; duplicate users were excluded. DryEyeRhythm was released on November 2, 2016; the study was conducted from November 2, 2016, to January 12, 2018. Exposures: DryEyeRhythm data were collected on demographics, medical history, lifestyle, subjective symptoms, and disease-specific symptoms, using the Ocular Surface Disease Index (100-point scale; scores 0-12 indicate normal, healthy eyes; 13-22, mild dry eye; 23-32, moderate dry eye; 33-100, severe dry eye symptoms), and the Zung Self-Rating Depression Scale (total of 20 items, total score ranging from 20-80, with >=40 highly suggestive of depression). Main Outcomes and Measures: Multivariate-adjusted logistic regression analysis was used to identify risk factors for symptomatic dry eye and to identify risk factors for undiagnosed symptomatic dry eye. Results: A total of 21 394 records were identified in our database; 4454 users, included 899 participants (27.3\%) with diagnosed and 2395 participants (72.7\%) with undiagnosed symptomatic dry eye, completed all questionnaires and their data were analyzed. A total of 2972 participants (66.7\%) were women; mean (SD) age was 27.9 (12.6) years. The identified risk factors for symptomatic vs no symptomatic dry eye included younger age (odds ratio [OR], 0.99; 95\% CI, 0.987-0.999, P = .02), female sex (OR, 1.99; 95\% CI, 1.61-2.46; P \&lt; .001), pollinosis (termed hay fever on the questionnaire) (OR, 1.35; 95\% CI, 1.18-1.55; P \&lt; .001), depression (OR, 1.78; 95\% CI, 1.18-2.69; P = .006), mental illnesses other than depression or schizophrenia (OR, 1.87; 95\% CI, 1.24-2.82; P = .003), current contact lens use (OR, 1.27; 95\% CI, 1.09-1.48; P = .002), extended screen exposure (OR, 1.55; 95\% CI, 1.25-1.91; P \&lt; .001), and smoking (OR, 1.65; 95\% CI, 1.37-1.98; P \&lt; .001). The risk factors for undiagnosed vs diagnosed symptomatic dry eye included younger age (OR, 0.96; 95\% CI, 0.95-0.97; P \&lt; .001), male sex (OR, 0.55; 95\% CI, 0.42-0.72; P \&lt; .001), as well as absence of collagen disease (OR, 95\% CI, 0.23; 0.09-0.60; P = .003), mental illnesses other than depression or schizophrenia (OR, 0.50; 95\% CI, 0.36-0.69; P \&lt; .001), ophthalmic surgery other than cataract surgery and laser-assisted in situ keratomileusis (OR, 0.41; 95\% CI, 0.27-0.64; P \&lt; .001), and current (OR, 0.64; 95\% CI, 0.54-0.77; P \&lt; .001) or past (OR, 0.45; 95\% CI, 0.34-0.58; P \&lt; .001) contact lens use. Conclusions and Relevance: This study{\textquoteright}s findings suggest that crowdsourced research identified individuals with diagnosed and undiagnosed symptomatic dry eye and the associated risk factors. These findings could play a role in earlier prevention or more effective interventions for dry eye disease.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.4815},
	author = {Inomata, Takenori and Iwagami, Masao and Nakamura, Masahiro and Shiang, Tina and Yoshimura, Yusuke and Fujimoto, Keiichi and Okumura, Yuichi and Eguchi, Atsuko and Iwata, Nanami and Miura, Maria and Hori, Satoshi and Hiratsuka, Yoshimune and Uchino, Miki and Tsubota, Kazuo and Dana, Reza and Murakami, Akira}
}
@article {1213831,
	title = {Scaling and maintenance of corneal thickness during aging},
	journal = {PLoS One},
	volume = {12},
	number = {10},
	year = {2017},
	month = {2017},
	pages = {e0185694},
	abstract = {Corneal thickness is tightly regulated by its boundary endothelial and epithelial layers. The regulated set-point of corneal thickness likely shows inter-individual variations, changes by age, and response to stress. Using anterior segment-optical coherence tomography, we measure murine central corneal thickness and report on body size scaling of murine central corneal thickness during aging. For aged-matched mice, we find that corneal thickness depends on sex and strain. To shed mechanistic insights into these anatomical changes, we measure epithelial layer integrity and endothelial cell density during the life span of the mice using corneal fluorescein staining and in vivo confocal microscopy, respectively and compare their trends with that of the corneal thickness. Cornea thickness increases initially (1 month: 114.7 {\textpm} 3.0 μm, 6 months: 126.3 {\textpm} 1.6 μm), reaches a maximum (9 months: 129.3 {\textpm} 4.4 μm) and then reduces (12 months: 127 {\textpm} 2.9 μm, 13 months: 119.5 {\textpm} 7.6 μm, 14 months: 110.6 {\textpm} 10.6 μm), while the body size (weight) increases with age. We find that endothelial cell density reduces from 2 months old to 8 months old as the mice age and epithelial layer accumulates damages within this time frame. Finally, we compare murine corneal thickness with those of several other mammals including humans and show that corneal thickness has an allometric scaling with body size. Our results have relevance for organ size regulation, translational pharmacology, and veterinary medicine.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0185694},
	author = {Inomata, Takenori and Mashaghi, Alireza and Hong, Jiaxu and Nakao, Takeshi and Dana, Reza}
}
@article {1517200,
	title = {Stratification of Individual Symptoms of Contact Lens-Associated Dry Eye Using the iPhone App DryEyeRhythm: Crowdsourced Cross-Sectional Study},
	journal = {J Med Internet Res},
	volume = {22},
	number = {6},
	year = {2020},
	month = {2020 Jun 26},
	pages = {e18996},
	abstract = {BACKGROUND: Discontinuation of contact lens use is mainly caused by contact lens-associated dry eye. It is crucial to delineate contact lens-associated dry eye{\textquoteright}s multifaceted nature to tailor treatment to each patient{\textquoteright}s individual needs for future personalized medicine. OBJECTIVE: This paper aims to quantify and stratify individual subjective symptoms of contact lens-associated dry eye and clarify its risk factors for future personalized medicine using the smartphone app DryEyeRhythm (Juntendo University). METHODS: This cross-sectional study included iPhone (Apple Inc) users in Japan who downloaded DryEyeRhythm. DryEyeRhythm was used to collect medical big data related to contact lens-associated dry eye between November 2016 and January 2018. The main outcome measure was the incidence of contact lens-associated dry eye. Univariate and multivariate adjusted odds ratios of risk factors for contact lens-associated dry eye were determined by logistic regression analyses. The t-distributed Stochastic Neighbor Embedding algorithm was used to depict the stratification of subjective symptoms of contact lens-associated dry eye. RESULTS: The records of 4454 individuals (median age 27.9 years, SD 12.6), including 2972 female participants (66.73\%), who completed all surveys were included in this study. Among the included participants, 1844 (41.40\%) were using contact lenses, and among those who used contact lenses, 1447 (78.47\%) had contact lens-associated dry eye. Multivariate adjusted odds ratios of risk factors for contact lens-associated dry eye were as follows: younger age, 0.98 (95\% CI 0.96-0.99); female sex, 1.53 (95\% CI 1.05-2.24); hay fever, 1.38 (95\% CI 1.10-1.74); mental illness other than depression or schizophrenia, 2.51 (95\% CI 1.13-5.57); past diagnosis of dry eye, 2.21 (95\% CI 1.63-2.99); extended screen exposure time \&gt;8 hours, 1.61 (95\% CI 1.13-2.28); and smoking, 2.07 (95\% CI 1.49-2.88). The t-distributed Stochastic Neighbor Embedding analysis visualized and stratified 14 groups based on the subjective symptoms of contact lens-associated dry eye. CONCLUSIONS: This study identified and stratified individuals with contact lens-associated dry eye and its risk factors. Data on subjective symptoms of contact lens-associated dry eye could be used for prospective prevention of contact lens-associated dry eye progression.},
	issn = {1438-8871},
	doi = {10.2196/18996},
	author = {Inomata, Takenori and Nakamura, Masahiro and Iwagami, Masao and Midorikawa-Inomata, Akie and Sung, Jaemyoung and Fujimoto, Keiichi and Okumura, Yuichi and Eguchi, Atsuko and Iwata, Nanami and Miura, Maria and Fujio, Kenta and Nagino, Ken and Hori, Satoshi and Tsubota, Kazuo and Dana, Reza and Murakami, Akira}
}
@article {1528408,
	title = {Clinical and Prodromal Ocular Symptoms in Coronavirus Disease: A Systematic Review and Meta-Analysis},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {10},
	year = {2020},
	month = {2020 08 03},
	pages = {29},
	abstract = {Purpose: This systematic review aimed to determine currently reported clinical and prodromal ocular symptoms in patients with coronavirus disease 2019 (COVID-19). Methods: An online article search was performed in PubMed and EMBASE. Altogether 15 studies (retrospective, prospective, or case studies) involving 1533 patients with COVID-19, reporting on ocular symptoms, and with outcome data available were identified. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Study-specific estimates (incidence rates of ocular symptoms in patients with COVID-19) of cases were combined using one-group meta-analysis in a random-effects model. Results: Of all included studies, 11.2\% (95\% confidence interval, 5.5-16.9; 78/1526 cases) reported ocular symptoms. The most common ocular finding was conjunctivitis. Prodromal ocular symptoms occurred in 12.5\% (13/104 cases) of patients with COVID-19. Positive real-time polymerase chain reaction results were obtained for 16.7\% (10/60 cases) of conjunctival samples and 0\% (0/17 cases) of tear samples. Twelve ocular conjunctival swab samples tested positive for SARS-CoV-2. Ten cases were from subjects showing ocular symptoms (16.7\%, 10/60 cases), and the remaining two cases were from subjects without ocular manifestation (1.8\%, 2/113 cases). Limitations included the short study period, small sample size, findings were limited to the Asian population, only seven articles included ophthalmologic examination details, and there is currently no consensus on COVID-19 management. Conclusions: Ocular symptoms may occur in the presymptomatic phase as a prodromal symptom (12.5\%, 13/104 cases), suggesting the possibility of viral transmission from the conjunctiva.},
	issn = {1552-5783},
	doi = {10.1167/iovs.61.10.29},
	author = {Inomata, Takenori and Kitazawa, Koji and Kuno, Toshiki and Sung, Jaemyoung and Nakamura, Masahiro and Iwagami, Masao and Takagi, Hisato and Midorikawa-Inomata, Akie and Zhu, Jun and Fujimoto, Keiichi and Okumura, Yuichi and Miura, Maria and Fujio, Kenta and Hirosawa, Kunihiko and Akasaki, Yasutsugu and Kuwahara, Mizu and Dana, Reza and Murakami, Akira}
}
@article {1504081,
	title = {Association between dry eye and depressive symptoms: Large-scale crowdsourced research using the DryEyeRhythm iPhone application},
	journal = {Ocul Surf},
	volume = {18},
	number = {2},
	year = {2020},
	month = {2020 Apr},
	pages = {312-319},
	abstract = {PURPOSE: Dry eye (DE) disease and depression are increasing in modern times. We investigated the association between DE and depressive symptoms using the iPhone application, DryEyeRhythm. METHODS: This large-scale crowdsourced observational study was conducted within iPhone users in Japan who downloaded DryEyeRhythm. Participants with a Zung Self-rating Depression Scale (SDS) score\&nbsp;>=\&nbsp;40 were defined as having depressive symptoms, and those with an Ocular Surface Disease Index (OSDI) score\&nbsp;>=\&nbsp;13 were defined as having DE symptoms (mild, 13-22; moderate, 23-32; and severe, 33-100). We compared SDS scores between participants with normal eye and mild, moderate, and severe OSDI-based DE symptoms. Logistic regression analyses were used to determine the association between DE severity and depressive symptoms after adjustment for demographic characteristics, medical history, and lifestyle habits. RESULTS: This study included 4454 participants (mean age, 27.9\&nbsp;{\textpm}\&nbsp;12.6 years; female, 66.7\%). Participants with SDS scores >=40 accounted for 58.2\%, 70.9\%, 79.4\%, and 85.0\% of normal controls and participants with mild, moderate, and severe DE symptoms, respectively (P trend\&nbsp;\&lt;\&nbsp;0.001). The adjusted odds ratios (95\% confidence interval) for depressive symptoms (SDS score of >=40) were 1.62 (1.35-1.95) for mild, 2.39 (1.92-2.97) for moderate, and 3.29 (2.70-4.00) for severe DE symptoms. CONCLUSION: This large-scale crowdsourced clinical study using DryEyeRhythm suggests that depressive symptoms are more common in individuals with more severe DE symptoms. DryEyeRhythm could play a role in earlier prevention or future prospective interventions for depressive symptoms in individuals with DE symptoms.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.02.007},
	author = {Inomata, Takenori and Iwagami, Masao and Nakamura, Masahiro and Shiang, Tina and Fujimoto, Keiichi and Okumura, Yuichi and Iwata, Nanami and Fujio, Kenta and Hiratsuka, Yoshimune and Hori, Satoshi and Tsubota, Kazuo and Dana, Reza and Murakami, Akira}
}
@article {1402577,
	title = {Risk Factors for Severe Dry Eye Disease: Crowdsourced Research Using DryEyeRhythm},
	journal = {Ophthalmology},
	volume = {126},
	number = {5},
	year = {2019},
	month = {2019 May},
	pages = {766-768},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.12.013},
	author = {Inomata, Takenori and Nakamura, Masahiro and Iwagami, Masao and Shiang, Tina and Yoshimura, Yusuke and Fujimoto, Keiichi and Okumura, Yuichi and Eguchi, Atsuko and Iwata, Nanami and Miura, Maria and Hori, Satoshi and Hiratsuka, Yoshimune and Uchino, Miki and Tsubota, Kazuo and Dana, Reza and Murakami, Akira}
}
@article {1626099,
	title = {Smartphone-based digital phenotyping for dry eye toward P4 medicine: a crowdsourced cross-sectional study},
	journal = {NPJ Digit Med},
	volume = {4},
	number = {1},
	year = {2021},
	month = {2021 Dec 20},
	pages = {171},
	abstract = {Multidimensional integrative data analysis of digital phenotyping is crucial for elucidating the pathologies of multifactorial and heterogeneous diseases, such as the dry eye (DE). This crowdsourced cross-sectional study explored a novel smartphone-based digital phenotyping strategy to stratify and visualize the heterogenous DE symptoms into distinct subgroups. Multidimensional integrative data were collected from 3,593 participants between November 2016 and September 2019. Dimension reduction via Uniform Manifold Approximation and Projection stratified the collected data into seven clusters of symptomatic DE. Symptom profiles and risk factors in each cluster were identified by hierarchical heatmaps and multivariate logistic regressions. Stratified DE subgroups were visualized by chord diagrams, co-occurrence networks, and Circos plot analyses to improve interpretability. Maximum blink interval was reduced in clusters 1, 2, and 5 compared to non-symptomatic DE. Clusters 1 and 5 had severe DE symptoms. A data-driven multidimensional analysis with digital phenotyping may establish predictive, preventive, personalized, and participatory medicine.},
	issn = {2398-6352},
	doi = {10.1038/s41746-021-00540-2},
	author = {Inomata, Takenori and Nakamura, Masahiro and Sung, Jaemyoung and Midorikawa-Inomata, Akie and Iwagami, Masao and Fujio, Kenta and Akasaki, Yasutsugu and Okumura, Yuichi and Fujimoto, Keiichi and Eguchi, Atsuko and Miura, Maria and Nagino, Ken and Shokirova, Hurramhon and Zhu, Jun and Kuwahara, Mizu and Hirosawa, Kunihiko and Dana, Reza and Murakami, Akira}
}
@article {961716,
	title = {Impaired Function of Peripherally Induced Regulatory T Cells in Hosts at High Risk of Graft Rejection.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016 Dec 23},
	pages = {39924},
	abstract = {Regulatory T cells (Tregs) are crucial for allograft survival. Tregs can be divided into thymus-derived natural Tregs (tTregs) and peripherally-derived induced Tregs (pTregs). Here, we determine whether the suppressive function of Treg subsets is hampered in hosts who are at high risk for rejecting their graft. To induce graft beds that promote high risk of transplant rejection, intrastromal corneal sutures were placed two weeks prior to the transplant procedure in mice. We demonstrate that in high-risk recipients the frequencies and function of pTregs (but not tTregs) are suppressed. Reduced function of pTregs correlated with decreased expression of CTLA-4, interleukin-10, and transforming growth factor-β. Adoptive transfer of pTregs from mice at low risk of subsequent graft rejection is able to rescue graft survival in recipients that are at high risk of rejecting their grafts. Our data suggest that impaired function of pTregs, but not tTregs, mediates the loss of immune tolerance and promotes allograft rejection.},
	issn = {2045-2322},
	doi = {10.1038/srep39924},
	author = {Inomata, Takenori and Hua, Jing and Di Zazzo, Antonio and Dana, Reza}
}
@article {1213826,
	title = {Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection},
	journal = {Cornea},
	volume = {37},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {95-101},
	abstract = {PURPOSE: To assess the effect of dry eye disease (DED) in graft donors on dendritic cell (DC) maturation, host T-cell sensitization, and corneal allograft rejection. METHODS: Corneas of control (healthy donor) and DED mice (C57BL/6) were transplanted onto fully allogeneic naive BALB/c recipients (n = 10 mice/group). Long-term allograft survival was evaluated for 8 weeks. Corneas and draining lymph nodes (dLNs) were harvested at posttransplantation day 14 (n = 5 mice/group). The frequencies of MHCII CD11c DCs in the donor corneas and host dLNs and the frequencies of interferon (IFN)-γ and IL-17 CD4 T cells and Foxp3 expression by Tregs in host dLNs were investigated using flow cytometry. The enzyme-linked immunospot assay was used to assess host T-cell allosensitization through direct and indirect pathways (n = 3/group). RESULTS: Recipients of DED donor corneas showed significantly reduced graft survival (10\%) compared with control mice (50\% survival, P = 0.022), and had significantly increased frequencies of mature DCs in the grafted cornea (DED donor 44.0\% {\textpm} 0.36\% vs. healthy donor 35.4 {\textpm} 0.5\%; P \&lt; 0.0001) and host dLNs (DED donor 25.1\% {\textpm} 0.66\% vs. healthy donor 13.7\% {\textpm} 1.6\%; P = 0.005). Frequencies of IFN-γ and IL-17 T cells were increased in the dLNs of recipients of DED corneas, whereas the expression (mean fluorescence intensity) of Foxp3 in Tregs was decreased significantly in these mice (DED donor 6004 {\textpm} 193 vs. healthy donor 6806 {\textpm} 81; P = 0.0002). Enzyme-linked immunospot analysis showed that the direct pathway of allosensitization was significantly amplified in recipients of grafts with DED (P = 0.0146). CONCLUSIONS: Our results indicate that DED in the donor is a significant risk factor for subsequent corneal allograft rejection.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001400},
	author = {Inomata, Takenori and Hua, Jing and Nakao, Takeshi and Shiang, Tina and Chiang, Homer and Amouzegar, Afsaneh and Dana, Reza}
}
@article {1109811,
	title = {Pre-banking microbial contamination of donor conjunctiva and storage medium for penetrating keratoplasty},
	journal = {Jpn J Ophthalmol},
	year = {2017},
	month = {2017 Jun 08},
	abstract = {PURPOSE: The aims of this study were to investigate the incidence of positive donor tissue cultures before transfer to preservation medium (Optisol{\texttrademark}-GS) for penetrating keratoplasty, to verify the efficacy of antibiotics contained in Optisol{\texttrademark}-GS by examining the drug susceptibility and to assess the relationship between the results of our microbial assessments as well as donor factors and the incidence of contamination. METHODS: We conducted a retrospective, cross-sectional study using Juntendo Eye Bank records for all corneal transplantations. Two hundred donor conjunctiva harvestings and storage medium (EP-II({\textregistered})) cultures were performed between July 2008 and June 2011. We analyzed the associations between donor factors (age, gender, history of cataract surgery, death-to-preservation interval, cause of death) and contamination rates using multivariate analysis by the generalized estimating equation model. RESULTS: We obtained positive bacterial cultures from 154 of the 200 eyes (77.0\%). The isolated bacteria were indigenous, such as coagulase-negative Staphylococci, Corynebacterium sp., and methicillin-resistant Staphylococcus aureus (MRSA). There was significant resistance to levofloxacin (18 eyes, 9.0\%) and gentamicin (12 eyes, 6.0\%), and no vancomycin-resistant bacteria were detected. The donor factors did not correlate with the prevalence of bacterial contamination in our criteria. CONCLUSIONS: Pre-banking microbial assessment allows for microbial detection, bacterial susceptibility and resistance testing. This is useful for developing preservation mediums containing effective spectrum antibiotic agents for high quality control of corneal banking.},
	issn = {1613-2246},
	doi = {10.1007/s10384-017-0521-1},
	author = {Inomata, Takenori and Ono, Koichi and Matsuba, Tsuyoshi and Shiang, Tina and Di Zazzo, Antonio and Nakatani, Satoru and Yamaguchi, Masahiro and Ebihara, Nobuyuki and Murakami, Akira}
}
@article {341701,
	title = {Long-term Effects of Therapy with Ranibizumab on Diabetic Retinopathy Severity and Baseline Risk Factors for Worsening Retinopathy.},
	journal = {Ophthalmology},
	year = {2014},
	month = {2014 Nov 18},
	abstract = {PURPOSE: To assess the effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity when administered for up to 3 years, evaluate the effect of delayed initiation of ranibizumab therapy on DR severity, and identify baseline patient characteristics associated with the development of proliferative DR (PDR). DESIGN: Exploratory analyses of phase III, randomized, double-masked, sham-controlled multicenter clinical trials. PARTICIPANTS: Adults with diabetic macular edema (DME) (N\&nbsp;= 759), baseline best-corrected visual acuity 20/40 to 20/320 Snellen equivalent, and central foveal thickness >=275 μm. METHODS: Patients were randomized to monthly 0.3 or 0.5 mg ranibizumab or sham injections. Sham participants could switch to 0.5 mg ranibizumab during the third year (sham/0.5 mg crossover). Baseline risk factors were evaluated to explore potential associations with development of PDR. Time to first development of PDR was analyzed by Kaplan-Meier methods to calculate cumulative probabilities by group. MAIN OUTCOME MEASURES: Study eye change on the Early Treatment Diabetic Retinopathy Study severity scale and a composite clinical outcome evaluating progression to PDR based on photographic changes plus clinically important events defining PDR. RESULTS: At month 36, a greater proportion of ranibizumab-treated eyes had >=2- or >=3-step DR improvement compared with sham/0.5 mg crossover. A >=3-step improvement was achieved at 36 months by 3.3\%, 15.0\%, and 13.2\% of sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab-treated eyes, respectively (P \&lt; 0.0001). Through 36 months, 39.1\% of eyes in the sham/0.5 mg group developed PDR, as measured by composite outcome, compared with 18.3\% and 17.1\% of eyes treated with 0.3 or 0.5 mg ranibizumab, respectively. The presence of macular capillary nonperfusion at baseline seems to be associated with progression to PDR in ranibizumab-treated eyes but did not meaningfully influence visual acuity improvement in eyes with DME after ranibizumab therapy. CONCLUSIONS: Ranibizumab, as administered to patients with DME for 12 to 36 months in these studies, can both improve DR severity and prevent worsening. Prolonged delays in initiation of ranibizumab therapy may limit this therapeutic effect. Although uncommon, the development of PDR still occurs in a small percentage of eyes undergoing anti-vascular endothelial growth factor therapy and may be related to the presence of macular nonperfusion.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.08.048},
	author = {Ip, Michael S and Domalpally, Amitha and Sun, Jennifer K and Ehrlich, Jason S}
}
@article {313256,
	title = {Coexpression of three opsins in cone photoreceptors of the salamander Ambystoma tigrinum},
	journal = {J Comp Neurol},
	volume = {522},
	number = {10},
	year = {2014},
	month = {2014 Jul 01},
	pages = {2249-65},
	abstract = {Although more than one type of visual opsin is present in the retina of most vertebrates, it was thought that each type of photoreceptor expresses only one opsin. However, evidence has accumulated that some photoreceptors contain more than one opsin, in many cases as a result of a developmental transition from the expression of one opsin to another. The salamander UV-sensitive (UV) cone is particularly notable because it contains three opsins (Makino and Dodd [1996] J Gen Physiol 108:27-34). Two opsin types are expressed at levels more than 100 times lower than the level of the primary opsin. Here, immunohistochemical experiments identified the primary component as a UV cone opsin and the two minor components as the short wavelength-sensitive (S) and long wavelength-sensitive (L) cone opsins. Based on single-cell recordings of 156 photoreceptors, the presence of three components in UV cones of hatchlings and terrestrial adults ruled out a developmental transition. There was no evidence for multiple opsin types within rods or S cones, but immunohistochemistry and partial bleaching in conjunction with single-cell recording revealed that both single and double L cones contained low levels of short wavelength-sensitive pigments in addition to the main L visual pigment. These results raise the possibility that coexpression of multiple opsins in other vertebrates was overlooked because a minor component absorbing at short wavelengths was masked by the main visual pigment or because the expression level of a component absorbing at long wavelengths was exceedingly low.},
	keywords = {Ambystoma, Animals, Immunohistochemistry, Microelectrodes, Opsins, Photic Stimulation, Retinal Cone Photoreceptor Cells, Retinal Pigments, Retinal Rod Photoreceptor Cells, Ultraviolet Rays, Vision, Ocular},
	issn = {1096-9861},
	doi = {10.1002/cne.23531},
	author = {Isayama, Tomoki and Chen, Ying and Kono, Masahiro and Fabre, Eduard and Slavsky, Michael and DeGrip, Willem J and Ma, Jian-Xing and Crouch, Rosalie K and Makino, Clint L}
}
@article {1154936,
	title = {What is changing when: Decoding visual information in movies from human intracranial recordings},
	journal = {Neuroimage},
	volume = {180},
	number = {Pt A},
	year = {2018},
	month = {2018 Oct 15},
	pages = {147-159},
	abstract = {The majority of visual recognition studies have focused on the neural responses to repeated presentations of static stimuli with abrupt and well-defined onset and offset times. In contrast, natural vision involves unique renderings of visual inputs that are continuously changing without explicitly defined temporal transitions. Here we considered commercial movies as a coarse proxy to natural vision. We recorded intracranial field potential signals from 1,284 electrodes implanted in 15 patients with epilepsy while the subjects passively viewed commercial movies. We could rapidly detect large changes in the visual inputs within approximately 100\&nbsp;ms of their occurrence, using exclusively field potential signals from ventral visual cortical areas including the inferior temporal gyrus and inferior occipital gyrus. Furthermore, we could decode the content of those visual changes even in a single movie presentation, generalizing across the wide range of transformations present in a movie. These results present a methodological framework for studying cognition during dynamic and natural vision.},
	issn = {1095-9572},
	doi = {10.1016/j.neuroimage.2017.08.027},
	author = {Isik, Leyla and Singer, Jedediah and Madsen, Joseph R and Kanwisher, Nancy and Kreiman, Gabriel}
}
@article {1059761,
	title = {Tissue Harvesting Site and Culture Medium Affect Attachment, Growth, and Phenotype of Ex Vivo Expanded Oral Mucosal Epithelial Cells},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Apr 06},
	pages = {674},
	abstract = {Transplantation of cultured oral mucosal epithelial cells (OMECs) is a promising treatment strategy for limbal stem cell deficiency. In order to improve the culture method, we investigated the effects of four culture media and tissue harvesting sites on explant attachment, growth, and phenotype of OMECs cultured from Sprague-Dawley rats. Neither choice of media or harvesting site impacted the ability of the explants to attach to the culture well. Dulbecco{\textquoteright}s modified Eagle{\textquoteright}s medium/Ham{\textquoteright}s F12 (DMEM) and Roswell Park Memorial Institute 1640 medium (RPMI) supported the largest cellular outgrowth. Fold outgrowth was superior from LL explants compared to explants from the buccal mucosa (BM), HP, and transition zone of the lower lip (TZ) after six-day culture. Putative stem cell markers were detected in cultures grown in DMEM and RPMI. In DMEM, cells from TZ showed higher colony-forming efficiency than LL, BM, and HP. In contrast to RPMI, DMEM both expressed the putative stem cell marker Bmi-1 and yielded cell colonies. Our data suggest that OMECs from LL and TZ cultured in DMEM give rise to undifferentiated cells with high growth capacity, and hence are the most promising for treatment of limbal stem cell deficiency.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-00417-z},
	author = {Islam, Rakibul and Eidet, Jon Roger and Badian, Reza A and Lippestad, Marit and Messelt, Edward and Griffith, May and Dartt, Darlene A. and Utheim, Tor Paaske}
}
@article {1452966,
	title = {Effects of gamma radiation sterilization on the structural and biological properties of decellularized corneal xenografts},
	journal = {Acta Biomater},
	volume = {96},
	year = {2019},
	month = {2019 Sep 15},
	pages = {330-344},
	abstract = {To address the shortcomings associated with corneal transplants, substantial efforts have been focused on developing new modalities such as xenotransplantion. Xenogeneic corneas are anatomically and biomechanically similar to the human cornea, yet their applications require prior decellularization to remove the antigenic components to avoid rejection. In the context of bringing decellularized corneas into clinical use, sterilization is a crucial step that determines the success of the transplantation. Well-standardized sterilization methods, such as gamma irradiation (GI), have been applied to decellularized porcine corneas (DPC) to avoid graft-associated infections in human recipients. However, little is known about the effect of GI on decellularized corneal xenografts. Here, we evaluated the radiation effect on the ultrastructure, optical, mechanical and biological properties of DPC. Transmission electron microscopy revealed that gamma irradiated decellularized porcine cornea (G-DPC) preserved its structural integrity. Moreover, the radiation did not reduce the optical properties of the tissue. Neither DPC nor G-DPC led to further activation of complement system compared to native porcine cornea when exposed to plasma. Although, DPC were mechanically comparable to the native tissue, GI increased the mechanical strength, tissue hydrophobicity and resistance to enzymatic degradation. Despite these changes, human corneal epithelial, stromal, endothelial and hybrid neuroblastoma cells grew and differentiated on DPC and G-DPC. Thus, GI may achieve effective tissue sterilization without affecting critical properties that are essential for corneal transplant survival.},
	issn = {1878-7568},
	doi = {10.1016/j.actbio.2019.07.002},
	author = {Islam, Mohammad Mirazul and Sharifi, Roholah and Mamodaly, Shamina and Islam, Rakibul and Nahra, Daniel and AbuSamra, Dina B and Hui, Pui Chuen and Adibnia, Yashar and Goulamaly, Mehdi and Paschalis, Eleftherios I and Cruzat, Andrea and Kong, Jing and Nilsson, Per H and Arg{\"u}eso, Pablo and Mollnes, Tom Eirik and Chodosh, James and Dohlman, Claes H and Gonzalez-Andrades, Miguel}
}
@article {468986,
	title = {Effect of Storage Temperature on Structure and Function of Cultured Human Oral Keratinocytes.},
	journal = {PLoS One},
	volume = {10},
	number = {6},
	year = {2015},
	month = {2015},
	pages = {e0128306},
	abstract = {PURPOSE/AIMS: To assess the effect of storage temperature on the viability, phenotype, metabolism, and morphology of cultured human oral keratinocytes (HOK). MATERIALS AND METHODS: Cultured HOK cells were stored in HEPES- and sodium bicarbonate-buffered Minimum Essential Medium (MEM) at nine temperatures in approximately 4{\textdegree}C increments from 4{\textdegree}C to 37{\textdegree}C for seven days. Cells were characterized for viability by calcein fluorescence, phenotype retention by immunocytochemistry, metabolic parameters (pH, glucose, lactate, and O2) within the storage medium by blood gas analysis, and morphology by scanning electron microscopy and light microscopy. RESULTS: Relative to the cultured, but non-stored control cells, a high percentage of viable cells were retained only in the 12{\textdegree}C and 16{\textdegree}C storage groups (85\%{\textpm}13\% and 68\%{\textpm}10\%, respectively). Expression of ABCG2, Bmi1, C/EBPδ, PCNA, cytokeratin 18, and caspase-3 were preserved after storage in the 5 groups between 4{\textdegree}C and 20{\textdegree}C, compared to the non-stored control. Glucose, pH and pO2 in the storage medium declined, whereas lactate increased with increasing storage temperature. Morphology was best preserved following storage of the three groups between 12{\textdegree}C, 16{\textdegree}C, and 20{\textdegree}C. CONCLUSION: We conclude that storage temperatures of 12{\textdegree}C and 16{\textdegree}C were optimal for maintenance of cell viability, phenotype, and morphology of cultured HOK. The storage method described in the present study may be applicable for other cell types and tissues; thus its significance may extend beyond HOK and the field of ophthalmology.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0128306},
	author = {Islam, Rakibul and Jackson, Catherine and Eidet, Jon R and Messelt, Edward B and Corraya, Rima Maria and Lyberg, Torstein and Griffith, May and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1645459,
	title = {Crosslinker-free collagen gelation for corneal regeneration},
	journal = {Sci Rep},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 Jun 01},
	pages = {9108},
	abstract = {Development of an artificial cornea can potentially fulfil the demand of donor corneas for transplantation as the number of donors is far less than needed to treat corneal blindness. Collagen-based artificial corneas stand out as a regenerative option, having promising clinical outcomes. Collagen crosslinked with chemical crosslinkers which modify the parent functional groups of collagen. However, crosslinkers are usually cytotoxic, so crosslinkers need to be removed from implants completely before application in humans. In addition, crosslinked products are mechanically weak and susceptible to enzymatic degradation. We developed a crosslinker free supramolecular gelation strategy using pyrene conjugated dipeptide amphiphile (PyKC) consisting of lysine and cysteine; in which collagen molecules are intertwined inside the PyKC network without any functional group modification of the collagen. The newly developed collagen implants (Coll-PyKC) are optically transparent and can effectively block UV light, are mechanically and enzymatically stable, and can be sutured. The Coll-PyKC implants support the growth and function of all corneal cells, trigger anti-inflammatory differentiation while suppressing the pro-inflammatory differentiation of human monocytes. Coll-PyKC implants can restrict human adenovirus propagation. Therefore, this crosslinker-free strategy can be used for the repair, healing, and regeneration of the cornea, and potentially other damaged organs of the body.},
	keywords = {Collagen, Cornea, Humans, Prostheses and Implants, Regeneration, Ultraviolet Rays},
	issn = {2045-2322},
	doi = {10.1038/s41598-022-13146-9},
	author = {Islam, Mohammad Mirazul and Chivu, Alexandru and AbuSamra, Dina B and Saha, Amrita and Chowdhuri, Sumit and Pramanik, Bapan and Dohlman, Claes H and Das, Debapratim and Arg{\"u}eso, Pablo and Rajaiya, Jaya and Patra, Hirak K and Chodosh, James}
}
@article {1586163,
	title = {Combined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responses},
	journal = {Acta Biomater},
	volume = {127},
	year = {2021},
	month = {2021 06},
	pages = {169-179},
	abstract = {Inadequate supplies of donor corneas have evoked an escalating interest in corneal xenotransplantation. However, innate immune responses contribute significantly to the mechanism of xenograft rejection. We hypothesized that complement component C5 and TLR co-receptor CD14 inhibition would inhibit porcine cornea induced innate immune responses. Therefore, we measured cytokine release in human blood, induced by three forms of corneal xenografts with or without inhibitors. Native porcine cornea (NPC) induced interleukins (IL-1β, IL-2, IL-6, IL-8, IL-1ra), chemokines (MCP-1, MIP-1α, MIP-1β) and other cytokines (TNF, G-CSF, INF-γ, FGF-basic). Decellularized (DPC) and gamma-irradiated cornea (g-DPC) elevated the release of those cytokines. C5-blockade by eculizumab inhibited all the cytokines except G-CSF when induced by NPC. However, C5-blockade failed to reduce DPC and g-DPC induced cytokines. Blockade of CD14 inhibited DPC-induced cytokines except for IL-8, MCP-1, MIP-1α, and G-CSF, while it inhibited all of them when induced by g-DPC. Combined blockade of C5 and CD14 inhibited the maximum number of cytokines regardless of the xenograft type. Finally, by using the TLR4 specific inhibitor Eritoran, we showed that TLR4 activation was the basis for the CD14 effect. Thus, blockade of C5, when combined with TLR4 inhibition, may have therapeutic potential in pig-to-human corneal xenotransplantation. STATEMENT OF SIGNIFICANCE: Bio-engineered corneal xenografts are on the verge of becoming a viable alternative to allogenic human-donor-cornea, but the host{\textquoteright}s innate immune response is still a critical barrier for graft acceptance. By overruling this barrier, limited graft availability would no longer be an issue for treating corneal diseases. We showed that the xenograft induced inflammation is initiated by the complement system and toll-like receptor activation. Intriguingly, the inflammatory response was efficiently blocked by simultaneously targeting bottleneck molecules in the complement system (C5) and the TLR co-receptor CD14 with pharmaceutical inhibitors. We postulate that a combination of C5 and CD14 inhibition could have a great therapeutic potential to overcome the immunologic barrier in pig-to-human corneal xenotransplantation.},
	keywords = {Animals, Complement C5, Cornea, Corneal Transplantation, Cytokines, Heterografts, Humans, Inflammation, Lipopolysaccharide Receptors, Swine, Transplantation, Heterologous},
	issn = {1878-7568},
	doi = {10.1016/j.actbio.2021.03.047},
	author = {Islam, Rakibul and Islam, Mohammad Mirazul and Nilsson, Per H and Mohlin, Camilla and Hagen, Kjersti Thorvaldsen and Paschalis, Eleftherios I and Woods, Russell L and Bhowmick, Sabuj Chandra and Dohlman, Claes H and Espevik, Terje and Chodosh, James and Gonzalez-Andrades, Miguel and Mollnes, Tom Eirik}
}
@article {1109816,
	title = {Quick-freeze/deep-etch electron microscopy visualization of the mouse posterior pole},
	journal = {Exp Eye Res},
	volume = {162},
	year = {2017},
	month = {2017 Sep},
	pages = {62-72},
	abstract = {The mouse is one of the most commonly used mammalian systems to study human diseases. In particular it has been an invaluable tool to model a multitude of ocular pathologies affecting the posterior pole. The aim of this study was to create a comprehensive map of the ultrastructure of the mouse posterior pole using the quick-freeze/deep-etch method (QFDE). QFDE can produce detailed three-dimensional images of tissue structure and macromolecular moieties, without many of the artifacts introduced by structure-altering post-processing methods necessary to perform conventional transmission electron microscopy (cTEM). A total of 18 eyes from aged C57BL6/J mice were enucleated and the posterior poles were processed, either intact or with the retinal pigment epithelium (RPE) cell layer removed, for imaging by either QFDE or cTEM. QFDE images were correlated with cTEM cross-sections and en face images through the outer retina. Nicely preserved outer retinal architecture was observed with both methods, however, QFDE provided excellent high magnification imaging, with greater detail, of the apical, central, and basal planes of the RPE. Furthermore, key landmarks within Bruch{\textquoteright}s membrane, choriocapillaris, choroid and sclera were characterized and identified. In this study we developed methods for preparing the outer retina of the mouse for evaluation with QFDE and provide a map of the ultrastructure and cellular composition of the outer posterior pole. This technique should be applicable for morphological evaluation of mouse models, in which detailed visualization of subtle ocular structural changes is needed or in cases where post-processing methods introduce unacceptable artifacts.},
	keywords = {Animals, Bruch Membrane, Choroid, Female, Imaging, Three-Dimensional, Male, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Models, Animal, Pigment Epithelium of Eye, Sclera},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2017.06.013},
	author = {Ismail, Ebraheim N and Ruberti, Jeffrey W and Malek, Goldis}
}
@article {836871,
	title = {Selection Pressure in the Human Adenovirus Fiber Knob Drives Cell Specificity in Epidemic Keratoconjunctivitis.},
	journal = {J Virol},
	volume = {90},
	number = {21},
	year = {2016},
	month = {2016 Nov 01},
	pages = {9598-9607},
	abstract = {Human adenoviruses (HAdVs) contain seven species (HAdV-A to -G), each associated with specific disease conditions. Among these, HAdV-D includes those viruses associated with epidemic keratoconjunctivitis (EKC), a severe ocular surface infection. The reasons for corneal tropism for some but not all HAdV-Ds are not known. The fiber protein is a major capsid protein; its C-terminal "knob" mediates binding with host cell receptors to facilitate subsequent viral entry. In a comprehensive phylogenetic analysis of HAdV-D capsid genes, fiber knob gene sequences of HAdV-D types associated with EKC formed a unique clade. By proteotyping analysis, EKC virus-associated fiber knobs were uniquely shared. Comparative structural modeling showed no distinct variations in fiber knobs of EKC types but did show variation among HAdV-Ds in a region overlapping with the known CD46 binding site in HAdV-B. We also found signature amino acid positions that distinguish EKC from non-EKC types, and by in vitro studies we showed that corneal epithelial cell tropism can be predicted by the presence of a lysine or alanine at residue 240. This same amino acid residue in EKC viruses shows evidence for positive selection, suggesting that evolutionary pressure enhances fitness in corneal infection, and may be a molecular determinant in EKC pathogenesis. IMPORTANCE: Viruses adapt various survival strategies to gain entry into target host cells. Human adenovirus (HAdV) types are associated with distinct disease conditions, yet evidence for connections between genotype and cellular tropism is generally lacking. Here, we provide a structural and evolutionary basis for the association between specific genotypes within HAdV species D and epidemic keratoconjunctivitis, a severe ocular surface infection. We find that HAdV-D fiber genes of major EKC pathogens, specifically the fiber knob gene region, share a distinct phylogenetic clade. Deeper analysis of the fiber gene revealed that evolutionary pressure at crucial amino acid sites has a significant impact on its structural conformation, which is likely important in host cell binding and entry. Specific amino acids in hot spot residues provide a link to ocular cell tropism and possibly to corneal pathogenesis.},
	issn = {1098-5514},
	doi = {10.1128/JVI.01010-16},
	author = {Ismail, Ashrafali M and Lee, Ji Sun and Dyer, David W and Seto, Donald and Rajaiya, Jaya and Chodosh, James}
}
@article {1302188,
	title = {Genomic analysis of a large set of currently-and historically-important human adenovirus pathogens},
	journal = {Emerg Microbes Infect},
	volume = {7},
	number = {1},
	year = {2018},
	month = {2018 Feb 07},
	pages = {10},
	abstract = {Human adenoviruses (HAdVs) are uniquely important "model organisms" as they have been used to elucidate fundamental biological processes, are recognized as complex pathogens, and are used as remedies for human health. As pathogens, HAdVs may effect asymptomatic or mild and severe symptomatic disease upon their infection of respiratory, ocular, gastrointestinal, and genitourinary systems. High-resolution genomic data have enhanced the understanding of HAdV epidemiology, with recombination recognized as an important and major pathway in the molecular evolution and genesis of emergent HAdV pathogens. To support this view and to actualize an algorithm for identifying, characterizing, and typing novel HAdVs, we determined the DNA sequence of 95 isolates from archives containing historically important pathogens and collections housing currently circulating strains to be sequenced. Of the 85 samples that were completely sequenced, 18 novel recombinants within species HAdV-B and D were identified. Two HAdV-D genomes were found to contain novel penton base and fiber genes with significant divergence from known molecular types. In this data set, we found additional isolates of HAdV-D53 and HAdV-D58, two novel genotypes recognized recently using genomics. This supports the thesis that novel HAdV genotypes are not limited to "one-time" appearances of the prototype but are of importance in HAdV epidemiology. These data underscore the significance of lateral genomic transfer in HAdV evolution and reinforce the potential public health impact of novel genotypes of HAdVs emerging in the population.},
	issn = {2222-1751},
	doi = {10.1038/s41426-017-0004-y},
	author = {Ismail, Ashrafali M and Cui, Tiange and Dommaraju, Kalpana and Singh, Gurdeep and Dehghan, Shoaleh and Seto, Jason and Shrivastava, Susmita and Fedorova, Nadia B and Gupta, Neha and Stockwell, Timothy B and Madupu, Ramana and Heim, Albert and Kajon, Adriana E and Romanowski, Eric G and Kowalski, Regis P and Malathi, Jambulingam and Therese, Kuzhanthai L and Madhavan, Hajib Narahari and Zhang, Qiwei and Ferreyra, Leonardo J and Jones, Morris S and Rajaiya, Jaya and Dyer, David W and Chodosh, James and Seto, Donald}
}
@article {1645466,
	title = {RANBP2 and USP9x regulate nuclear import of adenovirus minor coat protein IIIa},
	journal = {PLoS Pathog},
	volume = {18},
	number = {6},
	year = {2022},
	month = {2022 Jun},
	pages = {e1010588},
	abstract = {As intracellular parasites, viruses exploit cellular proteins at every stage of infection. Adenovirus outbreaks are associated with severe acute respiratory illnesses and conjunctivitis, with no specific antiviral therapy available. An adenoviral vaccine based on human adenovirus species D (HAdV-D) is currently in use for COVID-19. Herein, we investigate host interactions of HAdV-D type 37 (HAdV-D37) protein IIIa (pIIIa), identified by affinity purification and mass spectrometry (AP-MS) screens. We demonstrate that viral pIIIa interacts with ubiquitin-specific protease 9x (USP9x) and Ran-binding protein 2 (RANBP2). USP9x binding did not invoke its signature deubiquitination function but rather deregulated pIIIa-RANBP2 interactions. In USP9x-knockout cells, viral genome replication and viral protein expression increased compared to wild type cells, supporting a host-favored mechanism for USP9x. Conversely, RANBP2-knock down reduced pIIIa transport to the nucleus, viral genome replication, and viral protein expression. Also, RANBP2-siRNA pretreated cells appeared to contain fewer mature viral particles. Transmission electron microscopy of USP9x-siRNA pretreated, virus-infected cells revealed larger than typical paracrystalline viral arrays. RANBP2-siRNA pretreatment led to the accumulation of defective assembly products at an early maturation stage. CRM1 nuclear export blockade by leptomycin B led to the retention of pIIIa within cell nuclei and hindered pIIIa-RANBP2 interactions. In-vitro binding analyses indicated that USP9x and RANBP2 bind to C-terminus of pIIIa amino acids 386-563 and 386-510, respectively. Surface plasmon resonance testing showed direct pIIIa interaction with recombinant USP9x and RANBP2 proteins, without competition. Using an alternative and genetically disparate adenovirus type (HAdV-C5), we show that the demonstrated pIIIa interaction is also important for a severe respiratory pathogen. Together, our results suggest that pIIIa hijacks RANBP2 for nuclear import and subsequent virion assembly. USP9x counteracts this interaction and negatively regulates virion synthesis. This analysis extends the scope of known adenovirus-host interactions and has potential implications in designing new antiviral therapeutics.},
	issn = {1553-7374},
	doi = {10.1371/journal.ppat.1010588},
	author = {Ismail, Ashrafali M and Saha, Amrita and Lee, Ji S and Painter, David F and Chen, Yinghua and Singh, Gurdeep and Condezo, Gabriela N and Chodosh, James and San Mart{\'\i}n, Carmen and Rajaiya, Jaya}
}
@article {1402578,
	title = {Author Correction: Genomic analysis of a large set of currently-and historically-important human adenovirus pathogens},
	journal = {Emerg Microbes Infect},
	volume = {7},
	number = {1},
	year = {2018},
	month = {2018 Dec 08},
	pages = {208},
	abstract = {The original publication of this article [1] was missing the below author that made contributions to the research and the published article.},
	issn = {2222-1751},
	doi = {10.1038/s41426-018-0200-4},
	author = {Ismail, Ashrafali M and Cui, Tiange and Dommaraju, Kalpana and Singh, Gurdeep and Dehghan, Shoaleh and Seto, Jason and Shrivastava, Susmita and Fedorova, Nadia B and Gupta, Neha and Stockwell, Timothy B and Halpin, Rebecca and Madupu, Ramana and Heim, Albert and Kajon, Adriana E and Romanowski, Eric G and Kowalski, Regis P and Malathi, Jambulingam and Therese, Kuzhanthai L and Madhavan, Hajib Narahari and Zhang, Qiwei and Ferreyra, Leonardo J and Jones, Morris S and Rajaiya, Jaya and Dyer, David W and Chodosh, James and Seto, Donald}
}
@article {1517437,
	title = {Ultra-widefield autofluorescence imaging findings in retinoschisis, rhegmatogenous retinal detachment and combined retinoschisis retinal detachment},
	journal = {Acta Ophthalmol},
	year = {2020},
	author = {Navaratnam J and Salvanos P and Vavvas DG and Bragad{\'o}ttir R}
}
@article {1642383,
	title = {Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {63},
	number = {5},
	year = {2022},
	pages = {3},
	author = {Kim J and Kennedy Neary MT and Aschard H and Palakkamanil MM and Do R and Wiggs JL and Khawaja AP and Pasquale LR and Kang JH and International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucom}
}
@article {1586154,
	title = {Optical Coherence Tomography Angiography in Prematurity},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {264-269},
	abstract = {Purpose: During normal foveal development there is a close interaction between the neurosensory and vascular elements of the fovea making it vulnerable to prematurity and retinopathy of prematurity (ROP). We aim to assess this potential effect on foveal development in preterms evaluated simultaneously with both optical coherence tomography (OCT) and OCT angiography (OCTA).Method: Unrestricted literature search in the PubMed and Cochrane library databases yielded 20 distinct citations. Fifteen were relevant and reviewed.Results: In preterms, OCTA demonstrated a significant decrease in the foveal avascular zone area and an increase in foveal vessel density. OCT showed a decrease in foveal pit depth and an increase in the thickness of the subfoveal retinal layers. Some studies correlated these changes with reduced vision.Conclusion: Changes in the vascular and neurosensory retina were found in premature children. It remains unclear whether this is related to prematurity alone or ROP and its treatment.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1893760},
	author = {Jabroun, Mireille N and AlWattar, Bilal K and Fulton, Anne B}
}
@article {1732671,
	title = {Cataract Surgery in Patients With Uveitis Treated With Systemic Therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study: Risk Factors and Outcomes},
	journal = {Am J Ophthalmol},
	volume = {254},
	year = {2023},
	month = {2023 Oct},
	pages = {210-220},
	abstract = {PURPOSE: To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression. DESIGN: Cohort study of participants from a randomized clinical trial. METHODS: A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery. RESULTS: The cumulative incidence of cataract surgery was 43\% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age \&gt;50 years (hazard ratio [HR] 2.86, 95\% CI 1.52, 5.42; P\&nbsp;=\&nbsp;.001), topical corticosteroid use (time-updated HR 3.13, 95\% CI 1.42, 6.94; P\&nbsp;=\&nbsp;.005), glaucoma medication use (HR 2.75, 95\% CI 1.38, 5.47; P\&nbsp;=\&nbsp;.004), and possibly history of anterior chamber inflammation (HR 1.90, 95\% CI 0.95, 3.84; P\&nbsp;=\&nbsp;.07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data. CONCLUSIONS: Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.},
	keywords = {Cataract, Cohort Studies, Follow-Up Studies, Humans, Middle Aged, Panuveitis, Risk Factors, Steroids, Uveitis},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.06.023},
	author = {Jabs, Douglas A and Sugar, Elizabeth A and Burke, Alyce E and Altaweel, Michael M and Dunn, James P and Gangaputra, Sapna and Kempen, John H and Pepple, Kathryn L and Stawell, Richard J and Holbrook, Janet T and Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group}
}
@article {1154941,
	title = {Optimization of Storage Temperature for Retention of Undifferentiated Cell Character of Cultured Human Epidermal Cell Sheets},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Aug 15},
	pages = {8206},
	abstract = {Cultured epidermal cell sheets (CES) containing undifferentiated cells are useful for treating skin burns and have potential for regenerative treatment of other types of epithelial injuries. The undifferentiated phenotype is therefore important for success in both applications. This study aimed to optimize a method for one-week storage of CES for their widespread distribution and use in regenerative medicine. The effect of storage temperatures 4 {\textdegree}C, 8 {\textdegree}C, 12 {\textdegree}C, 16 {\textdegree}C, and 24 {\textdegree}C on CES was evaluated. Analyses included assessment of viability, mitochondrial reactive oxygen species (ROS), membrane damage, mitochondrial DNA (mtDNA) integrity, morphology, phenotype and cytokine secretion into storage buffer. Lowest cell viability was seen at 4 {\textdegree}C. Compared to non-stored cells, ABCG2 expression increased between temperatures 8-16 {\textdegree}C. At 24 {\textdegree}C, reduced ABCG2 expression coincided with increased mitochondrial ROS, as well as increased differentiation, cell death and mtDNA damage. P63, C/EBPδ, CK10 and involucrin fluorescence combined with morphology observations supported retention of undifferentiated cell phenotype at 12 {\textdegree}C, transition to differentiation at 16 {\textdegree}C, and increased differentiation at 24 {\textdegree}C. Several cytokines relevant to healing were upregulated during storage. Importantly, cells stored at 12 {\textdegree}C showed similar viability and undifferentiated phenotype as the non-stored control suggesting that this temperature may be ideal for storage of CES.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-08586-7},
	author = {Jackson, Catherine J and Reppe, Sjur and Eidet, Jon R and Eide, Lars and T{\o}nseth, Kim A and Bergersen, Linda H and Dartt, Darlene A. and Griffith, May and Utheim, Tor P}
}
@article {1478342,
	title = {Simple limbal epithelial transplantation: Current status and future perspectives},
	journal = {Stem Cells Transl Med},
	volume = {9},
	number = {3},
	year = {2020},
	month = {2020 Mar},
	pages = {316-327},
	abstract = {Damage to limbal stem cells as a result of injury or disease can lead to limbal stem cell deficiency (LSCD). This disease is characterized by decreased vision that is often painful and may progress to blindness. Clinical features include inflammation, neovascularization, and persistent cornea epithelial defects. Successful strategies for treatment involve transplantation of grafts harvested from the limbus of the alternate healthy eye, called conjunctival-limbal autograft (CLAU) and transplantation of limbal cell sheets cultured from limbal biopsies, termed cultured limbal epithelial transplantation (CLET). In 2012, Sangwan and colleagues presented simple limbal epithelial transplantation (SLET), a novel transplantation technique that combines the benefits of CLAU and CLET and avoids the challenges associated with both. In SLET a small biopsy from the limbus of the healthy eye is divided and distributed over human amniotic membrane, which is placed on the affected cornea. Outgrowth occurs from each small explant and a complete corneal epithelium is typically formed within 2 weeks. Advantages of SLET include reduced risk of iatrogenic LSCD occurring in the healthy cornea at harvest; direct transfer circumventing the need for cell culture; and the opportunity to perform biopsy harvest and transplantation in one operation. Success so far using SLET is comparable with CLAU and CLET. Of note, 336 of 404 (83\%) operations using SLET resulted in restoration of the corneal epithelium, whereas visual acuity improved in 258 of the 373 (69\%) reported cases. This review summarizes the results of 31 studies published on SLET since 2012. Progress, advantages, challenges, and suggestions for future studies are presented.},
	issn = {2157-6580},
	doi = {10.1002/sctm.19-0203},
	author = {Jackson, Catherine J and Myklebust Ern{\o}, Inger T and Ringstad, H{\r a}kon and T{\o}nseth, Kim A and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1354351,
	title = {Feasibility of a web-based survey of hallucinations and assessment of visual function in patients with Parkinson{\textquoteright}s disease},
	journal = {Interact J Med Res},
	volume = {3},
	number = {1},
	year = {2014},
	month = {2014 Jan 06},
	pages = {e1},
	abstract = {BACKGROUND: Patients with Parkinson{\textquoteright}s disease (PD) experience visual hallucinations, which may be related to decreased contrast sensitivity (ie, the ability to discern shades of grey). OBJECTIVE: The objective of this study was to investigate if an online research platform can be used to survey patients with Parkinson{\textquoteright}s disease regarding visual hallucinations, and also be used to assess visual contrast perception. METHODS: From the online patient community, PatientsLikeMe, 964 members were invited via email to participate in this study. Participants completed a modified version of the University of Miami Parkinson{\textquoteright}s disease hallucinations questionnaire and an online vision test. RESULTS: The study was completed by 27.9\% (269/964) of those who were invited: 56.9\% of this group had PD (153/269) and 43.1\% (116/269) were non-Parkinson{\textquoteright}s controls. Hallucinations were reported by 18.3\% (28/153) of the Parkinson{\textquoteright}s group. Although 10 subjects (9\%) in the control group reported experiencing hallucinations, only 2 of them actually described formed hallucinations. Participants with Parkinson{\textquoteright}s disease with a mean of 1.75 (SD 0.35) and the control group with a mean of 1.85 (SD 0.36) showed relatively good contrast perception as measured with the online letter test (P=.07). People who reported hallucinations showed contrast sensitivity levels that did not differ from levels shown by people without hallucinations (P=.96), although there was a trend towards lower contrast sensitivity in hallucinators. CONCLUSIONS: Although more Parkinson{\textquoteright}s responders reported visual hallucinations, a significant number of non-Parkinson{\textquoteright}s control group responders also reported visual hallucinations. The online survey method may have failed to distinguish between formed hallucinations, which are typical in Parkinson{\textquoteright}s disease, and non-formed hallucinations that have less diagnostic specificity. Multiple questions outlining the nature of the hallucinations are required. In a clinical interview, the specific nature of the hallucination would be further refined to rule out a vague description that does not indicate a true, formed visual hallucination. Contrary to previous literature, both groups showed relatively good contrast sensitivity, perhaps representing a ceiling effect or limitations of online testing conditions that are difficult to standardize. Steps can be taken in future trials to further standardize online visual function testing, to refine control group parameters and to take steps to rule out confounding variables such as comorbid disease that could be associated with hallucinations. Contacting subjects via an online health social network is a novel, cost-effective method of conducting vision research that allows large numbers of individuals to be contacted quickly, and refinement of questionnaires and visual function testing may allow more robust findings in future research.},
	issn = {1929-073X},
	doi = {10.2196/ijmr.2744},
	author = {Jackson, Mary Lou and Bex, Peter J and Ellison, James M and Wicks, Paul and Wallis, Jennifer}
}
@article {1538348,
	title = {Homologous Recombination Offers Advantages Over Transposition-Based Systems to Generate Recombinant Baculovirus for Adeno-Associated Viral Vector Production},
	journal = {Biotechnol J},
	year = {2020},
	month = {2020 Oct 16},
	pages = {e2000014},
	abstract = {Viral vectors have a great potential for gene delivery, but manufacturing at a pharmaceutical scale is a big challenge for the industry. The baculovirus-insect cell system is one of the most scalable platforms to produce clinical-grade recombinant Adeno-Associated Virus (rAAV) vectors. The standard procedure to generate recombinant baculovirus is based on Tn7 transposition which is time-consuming and still suffers technical constraints. Moreover, werecently showed that baculoviral sequences adjacent to the AAV ITRs are preferentially encapsidated into the rAAV vector particles. This observation raised concerns about safety for clinical applications due to the presence of bacterial and antibiotic resistance coding sequences with a Tn7-mediated system for the construction of baculoviruses reagents. Here, weinvestigated a faster and safer method based on homologous recombination (HR). First, weconfirmed the functionality of the inserted cassette and the absence of undesirable genes into HR-derived baculoviral genomes. Strikingly, wefound that the exogenous cassette showed increased stability over passages when using the HR system. Finally, wetested these materials to produce rAAV vectors. The baculoviruses originated from both systems lead to high rAAV vector genome yields, with the advantage of the HR system being exempted from undesirable bacterial genes which provides an additional level of safety for the manufacturing of rAAV vectors. Overall, this study highlights the importance of the upstream process and starting biologic materials to generate safer rAAV biotherapeutic products. This article is protected by copyright. All rights reserved.},
	issn = {1860-7314},
	doi = {10.1002/biot.202000014},
	author = {Jacob, Aur{\'e}lien and Brun, Laurie and Gil, Paloma Jim{\'e}nez and M{\'e}nard, Lucie and Bouzelha, Mohammed and Broucque, Fr{\'e}d{\'e}ric and Roblin, Aline and Vandenberghe, Luk H and Adjali, Oumeya and Robin, C{\'e}cile and Fran{\c c}ois, Achille and Blouin, V{\'e}ronique and Penaud-Budloo, Magalie and Ayuso, Eduard}
}
@article {1677721,
	title = {Performance of Automated Machine Learning for Diabetic Retinopathy Image Classification from Multi-field Handheld Retinal Images},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {703-712},
	abstract = {PURPOSE: To create and validate code-free automated deep learning models (AutoML) for diabetic retinopathy (DR) classification from handheld retinal images. DESIGN: Prospective development and validation of AutoML models for DR image classification. PARTICIPANTS: A total of 17 829 deidentified retinal images from 3566 eyes with diabetes, acquired using handheld retinal cameras in a community-based DR screening program. METHODS: AutoML models were generated based on previously acquired 5-field (macula-centered, disc-centered, superior, inferior, and temporal macula) handheld retinal images. Each individual image was labeled using the International DR and diabetic macular edema (DME) Classification Scale by 4 certified graders at a centralized reading center under oversight by a senior retina specialist. Images for model development were split 8-1-1 for training, optimization, and testing to detect referable DR ([refDR], defined as moderate nonproliferative DR or worse or any level of DME). Internal validation was performed using a published image set from the same patient population (N\&nbsp;= 450 images from 225 eyes). External validation was performed using a publicly available retinal imaging data set from the Asia Pacific Tele-Ophthalmology Society (N\&nbsp;= 3662 images). MAIN OUTCOME MEASURES: Area under the precision-recall curve (AUPRC), sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy, and F1 scores. RESULTS: Referable DR was present in 17.3\%, 39.1\%, and 48.0\% of the training set, internal validation, and external validation sets, respectively. The model{\textquoteright}s AUPRC was 0.995 with a precision and recall of 97\% using a score threshold of 0.5. Internal validation showed that SN, SP, PPV, NPV, accuracy, and F1 scores were 0.96 (95\% confidence interval [CI], 0.884-0.99), 0.98 (95\% CI, 0.937-0.995), 0.96 (95\% CI, 0.884-0.99), 0.98 (95\% CI, 0.937-0.995), 0.97, and 0.96, respectively. External validation showed that SN, SP, PPV, NPV, accuracy, and F1 scores were 0.94 (95\% CI, 0.929-0.951), 0.97 (95\% CI, 0.957-0.974), 0.96 (95\% CI, 0.952-0.971), 0.95 (95\% CI, 0.935-0.956), 0.97, and 0.96, respectively. CONCLUSIONS: This study demonstrates the accuracy and feasibility of code-free AutoML models for identifying refDR developed using handheld retinal imaging in a community-based screening program. Potentially, the use of AutoML may increase access to machine learning models that may be adapted for specific programs that are guided by the clinical need to rapidly address disparities in health care delivery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Humans, machine learning, Macular Edema, Prospective Studies, Retina},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.03.003},
	author = {Jacoba, Cris Martin P and Doan, Duy and Salongcay, Recivall P and Aquino, Lizzie Anne C and Silva, Joseph Paolo Y and Salva, Claude Michael G and Zhang, Dean and Alog, Glenn P and Zhang, Kexin and Locaylocay, Kaye Lani Rea B and Saunar, Aileen V and Ashraf, Mohamed and Sun, Jennifer K and Peto, Tunde and Aiello, Lloyd Paul and Silva, Paolo S}
}
@article {1632301,
	title = {Association of Maximizing Visible Retinal Area by Manual Eyelid Lifting With Grading of Diabetic Retinopathy Severity and Detection of Predominantly Peripheral Lesions When Using Ultra-Widefield Imaging},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {4},
	year = {2022},
	month = {2022 Apr 01},
	pages = {421-425},
	abstract = {Importance: Methods that increase visible retinal area (VRA; measured in millimeters squared) may improve identification of diabetic retinopathy (DR) lesions. Objective: To evaluate the association of dilation and manual eyelid lifting (MLL) with VRA on ultra-widefield imaging (UWFI) and the association of VRA with grading of DR severity and detection of predominantly peripheral lesions (PPLs). Design, Setting, and Participants: Retrospective, comparative case-control study at the Joslin Diabetes Center, Boston, Massachusetts. Nonmydriatic UWFI with MLL was acquired from a DR teleophthalmology program (Joslin Vision Network [JVN]). A second cohort of mydriatic UWFI was acquired at an academic retina practice (Beetham Eye Institute [BEI]) from November 6, 2017, to November 6, 2018, and with MLL thereafter until November 6, 2019. Fully automated algorithms determined VRA and hemorrhage and/or microaneurysm (HMA) counts. Predominantly peripheral lesions and HMAs were defined as present when at least 1 field had greater HMA number in the peripheral retina than within the corresponding Early Treatment Diabetic Retinopathy Study field. Participants included 3014 consecutive patients (5919 eyes) undergoing retinal imaging at JVN and BEI. Exposures: Dilation and MLL performed at the time of UWFI. Main Outcomes and Measures: Visible retinal area, DR severity, and presence of PPLs. Results: Of the 3014 participants, mean (SD) age was 56.1 (14.5) years, 1302 (43.2\%) were female, 2450 (81.3\%) were White, and mean (SD) diabetes duration was 15.9 (11.4) years. All images from 5919 eyes with UWFI were analyzed. Mean (SD) VRA was 665.1 (167.6) mm2 for all eyes (theoretical maximal VRA, 923.9 mm2), 550.8 (240.7) mm2 for nonmydriatic JVN with MLL (1418 eyes [24.0\%]), 688.1 (119.9) mm2 for mydriatic BEI images (3650 eyes [61.7\%]), and 757.0 (69.7) mm2 for mydriatic and MLL BEI images (851 eyes [14.4\%]). Dilation increased VRA by 25\% (P \&lt; .001) and MLL increased VRA an additional 10\% (P \&lt; .001). Nonmydriatic MLL increased VRA by 11.0\%. With MLL, HMA counts in UWFI fields increased by 41.7\% (from 4.8 to 6.8; P \&lt; .001). Visible retinal area was moderately associated with increasing PPL-HMA overall and in each cohort (all, r = 0.33; BEI, r = 0.29; JVN, r = 0.36; P \&lt; .001). In JVN images, increasing VRA was associated with more PPL-HMA (quartile 1 [Q1], 23.7\%; Q2, 45.8\%; Q3, 60.6\%; and Q4, 69.2\%; P \&lt; .001). Conclusions and Relevance: Using fully automated VRA and HMA detection algorithms, pupillary dilation and eyelid lifting were shown to substantially increase VRA and PLL-HMA detection. Given the importance of HMA and PPL for determining risk of DR progression, these findings emphasize the importance of maximizing VRA for optimal risk assessment in clinical trials and teleophthalmology programs.},
	keywords = {Case-Control Studies, Diabetes Mellitus, Diabetic Retinopathy, Eyelids, Female, Humans, Male, Microaneurysm, Middle Aged, Mydriatics, Ophthalmology, Retina, Retrospective Studies, Telemedicine},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.6363},
	author = {Jacoba, Cris Martin P and Ashraf, Mohamed and Cavallerano, Jerry D and Tolson, Ann M and Tolls, Dorothy and Pellegrini, Enrico and Fleming, Alan and Sun, Jennifer K and Aiello, Lloyd Paul and Silva, Paolo S}
}
@article {1667710,
	title = {Comparisons of handheld retinal imaging devices with ultrawide field images for determining diabetic retinopathy severity},
	journal = {Acta Ophthalmol},
	volume = {101},
	number = {6},
	year = {2023},
	month = {2023 Sep},
	pages = {670-678},
	abstract = {PURPOSE: To compare diabetic retinopathy (DR) severity identified on handheld retinal imaging with ultrawide field (UWF) images. METHODS: Mydriatic images of 225 eyes of 118 diabetic patients were prospectively imaged with the Aurora (AU) handheld retinal camera [5-field protocol (macula-centred, disc-centred, temporal, superior, inferior)] and compared with UWF images. Images were classified based on the international classification for DR. Sensitivity, specificity, kappa statistics (K/Kw) were calculated on an eye and person-level. RESULTS: Distribution of DR severity by AU/UWF images (\%) by eye was no DR 41.3/36.0, mild non-proliferative DR (NPDR) 18.7/17.8, moderate 10.2/10.7, severe 16.4/15.1, proliferative DR (PDR) 13.3/20.4. Agreement between UWF and AU was exact in 64.4\%, within 1-step 90.7\%, k\&nbsp;=\&nbsp;0.55 (95\% CI:0.45-0.65), and kw\&nbsp;=\&nbsp;0.79 (95\% CI:0.73-0.85) by eye, and exact in 68\%, within 1-step 92.9\%, k\&nbsp;=\&nbsp;0.58 (95\% CI:0.50-0.66), and kw\&nbsp;=\&nbsp;0.76 (95\% CI:0.70-0.81) by person. Sensitivity/specificity for any DR, refDR, vtDR and PDR were as follows: 0.90/0.83, 0.90/0.97, 0.82/0.95 and 0.69/1.00 by person and 0.86/0.90, 0.84/0.98, 0.75/0.95 and 0.63/0.99 by eye. Handheld imaging missed 37\% (17/46) eyes and 30.8\% (8/26) persons with PDR. Only 3.9\% (1/26) persons or 6.5\% (3/46) eyes with PDR were missed if a referral threshold of moderate NPDR was used. CONCLUSIONS: Data from this study show that comparing UWF and handheld images, when PDR was the referral threshold for handheld devices, 37.0\% of eyes or 30.8\% of patients with PDR were missed. Due to the identification of neovascular lesions outside of the handheld fields, lower referral thresholds are needed if handheld devices are used.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Diagnostic Imaging, Humans, Mydriatics, Retina, Sensitivity and Specificity},
	issn = {1755-3768},
	doi = {10.1111/aos.15651},
	author = {Jacoba, Cris Martin P and Salongcay, Recivall P and Aquino, Lizzie Anne C and Salva, Claude Michael G and Saunar, Aileen V and Alog, Glenn P and Peto, Tunde and Silva, Paolo S}
}
@article {1677711,
	title = {Effect of Accessible Nonmydriatic Retinal Imaging on Diabetic Retinopathy Surveillance Rates},
	journal = {Telemed J E Health},
	volume = {29},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1667-1672},
	abstract = {Purpose: To evaluate the impact on surveillance rates for diabetic retinopathy (DR) by providing nonmydriatic retinal imaging as part of comprehensive diabetes care at no cost to patients or insurers. Methods: A retrospective comparative cohort study was designed. Patients were imaged from April 1, 2016 to March 31, 2017 at a tertiary diabetes-specific academic medical center. Retinal imaging was provided without additional cost beginning October 16, 2016. Images were evaluated for DR and diabetic macular edema using standard protocol at a centralized reading center. Diabetes surveillance rates before and after no-cost imaging were compared. Results: A total of 759 and 2,080 patients respectively were imaged before and after offering no-cost retinal imaging. The difference represents a 274\% increase in the number of patients screened. Furthermore, there was a 292\% and 261\% increase in the number of eyes with mild DR and referable DR, respectively. In the comparative 6-month period, 92 additional cases of proliferative DR were identified, estimated to prevent 6.7 cases of severe visual loss with annual cost savings of $180,230 (estimated yearly cost of severe vision loss per person: $26,900). In patients with referable DR, self-awareness was low, with no significant difference in the before and after groups (39.4\% vs. 43.8\%, p = 0.3725). Conclusions: Providing retinal imaging as part of comprehensive diabetes care substantially increased the number of patients identified by nearly threefold. The data suggest that the removal of out-of-pocket costs substantially increased patient surveillance rates, which may translate to improved long-term patient outcomes.},
	keywords = {Cohort Studies, Diabetes Mellitus, Diabetic Retinopathy, Humans, Macular Edema, Photography, Retrospective Studies},
	issn = {1556-3669},
	doi = {10.1089/tmj.2022.0313},
	author = {Jacoba, Cris Martin P and Cavallerano, Jerry D and Tolston, Ann M and Silva, Paolo S}
}
@article {1664978,
	title = {Bias and Non-Diversity of Big Data in Artificial Intelligence: Focus on Retinal Diseases},
	journal = {Semin Ophthalmol},
	year = {2023},
	month = {2023 Jan 18},
	pages = {1-9},
	abstract = {Artificial intelligence (AI) applications in healthcare will have a potentially far-reaching impact on patient care, however issues regarding algorithmic bias and fairness have recently surfaced. There is a recognized lack of diversity in the available ophthalmic datasets, with 45\% of the global population having no readily accessible representative images, leading to potential misrepresentations of their unique anatomic features and ocular pathology. AI applications in retinal disease may show less accuracy with underrepresented populations that may further widen the gap of health inequality if left unaddressed. Beyond disease symptomatology, social determinants of health must be integrated into our current paradigms of disease understanding, with the goal of more personalized care. AI has the potential to decrease global healthcare inequality, but it will need to be based on a more diverse, transparent and responsible use of healthcare data.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2168486},
	author = {Jacoba, Cris Martin P and Celi, Leo Anthony and Lorch, Alice C and Fickweiler, Ward and Sobrin, Lucia and Gichoya, Judy Wawira and Aiello, Lloyd P and Silva, Paolo S}
}
@article {1586189,
	title = {Biomarkers for Progression in Diabetic Retinopathy: Expanding Personalized Medicine through Integration of AI with Electronic Health Records},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {250-257},
	abstract = {The goal of personalized diabetes eye care is to accurately predict in real-time the risk of diabetic retinopathy (DR) progression and visual loss. The use of electronic health records (EHR) provides a platform for artificial intelligence (AI) algorithms that predict DR progression to be incorporated into clinical decision-making. By implementing an algorithm on data points from each patient, their risk for retinopathy progression and visual loss can be modeled, allowing them to receive timely treatment. Data can guide algorithms to create models for disease and treatment that may pave the way for more personalized care. Currently, there exist numerous challenges that need to be addressed before reliably building and deploying AI algorithms, including issues with data quality, privacy, intellectual property, and informed consent.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1893351},
	author = {Jacoba, Cris Martin P and Celi, Leo Anthony and Silva, Paolo S}
}
@article {1490453,
	title = {[Recent Research Efforts to Achieve Neuroprotection, Progression and Treatment of Glaucoma]},
	journal = {Klin Monbl Augenheilkd},
	volume = {237},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {133-139},
	abstract = {Glaucoma is a neurodegenerative disease that leads to irreversible blindness over time. Its defining feature is the loss of retinal ganglion cells (RGCs) in the eye and their axons in the optic nerve. Increased intraocular pressure (IOP) is a major risk factor for the development of glaucoma, but is neither necessary nor sufficient for the disease and its progression; this motivates research and development of new strategies for the detection and treatment of glaucoma that focus on neuroprotection - protection of RGCs from dying. In addition, for diagnosis and treatment by reducing IOP, new approaches have been developed in recent years. This article reviews current theories of pathophysiological mechanisms underlying glaucoma and recent research - with a focus on neuroprotection and current preclinical and clinical studies to improve the diagnosis and treatment of glaucoma.},
	issn = {1439-3999},
	doi = {10.1055/a-1079-5778},
	author = {Jacobi, Anne and van Zyl, Tav{\'e}}
}
@article {382581,
	title = {Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels.},
	journal = {J Biol Chem},
	volume = {290},
	number = {10},
	year = {2015},
	month = {2015 Mar 6},
	pages = {6349-60},
	abstract = {Here we report that VEGF-A and IGF-1 differ in their ability to stabilize newly formed blood vessels and endothelial cell tubes. Although VEGF-A failed to support an enduring vascular response, IGF-1 stabilized neovessels generated from primary endothelial cells derived from various vascular beds and mouse retinal explants. In these experimental systems, destabilization/regression was driven by lysophosphatidic acid (LPA). Because previous studies have established that Erk antagonizes LPA-mediated regression, we considered whether Erk was an essential component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to stabilize neovessels when the Erk pathway was inhibited pharmacologically. Furthermore, stabilization was associated with prolonged Erk activity. In the presence of IGF-1, Erk activity persisted longer than in the presence of VEGF or LPA alone. These studies reveal that VEGF and IGF-1 can have distinct inputs in the angiogenic process. In contrast to VEGF, IGF-1 stabilizes neovessels, which is dependent on Erk activity and associated with prolonged activation.},
	issn = {1083-351X},
	doi = {10.1074/jbc.M114.634154},
	author = {Jacobo, Sarah Melissa P and Kazlauskas, Andrius}
}
@article {1363123,
	title = {Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1},
	journal = {Mol Cell Biol},
	volume = {33},
	number = {10},
	year = {2013},
	month = {2013 May},
	pages = {1976-90},
	abstract = {Synonymous single nucleotide polymorphisms (SNPs) within a transcript{\textquoteright}s coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1{\textquoteright}s conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1{\textquoteright}s putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1{\textquoteright}s abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD.},
	keywords = {Aged, Aged, 80 and over, Case-Control Studies, Cells, Cultured, Choroidal Neovascularization, Female, Genetic Association Studies, High-Temperature Requirement A Serine Peptidase 1, Homozygote, Humans, Insulin-Like Growth Factor I, Linkage Disequilibrium, Macular Degeneration, Male, Polymorphism, Single Nucleotide, Protein Binding, Protein Biosynthesis, Protein Interaction Domains and Motifs, Protein Stability, Proteolysis, Receptors, Somatomedin, Serine Endopeptidases, Signal Transduction, Trypsin},
	issn = {1098-5549},
	doi = {10.1128/MCB.01283-12},
	author = {Jacobo, Sarah Melissa P and Deangelis, Margaret M and Kim, Ivana K and Kazlauskas, Andrius}
}
@article {1364618,
	title = {Focus on molecules: HtrA1 and neovascular AMD},
	journal = {Exp Eye Res},
	volume = {94},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {4-5},
	keywords = {Gene Expression, High-Temperature Requirement A Serine Peptidase 1, Humans, Macular Degeneration, Polymorphism, Single Nucleotide, Protein Structure, Secondary, Serine Endopeptidases},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2010.07.006},
	author = {Jacobo, Sarah Melissa P and Kazlauskas, Andrius}
}
@article {1661820,
	title = {Refractive Errors Preferred Practice Pattern{\textregistered}},
	journal = {Ophthalmology},
	volume = {130},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {P1-P60},
	keywords = {Humans, Refractive Errors, Sex Distribution},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.10.031},
	author = {Jacobs, Deborah S and Afshari, Natalie A and Bishop, Rachel J and Keenan, Jeremy D and Lee, Jimmy and Shen, Tueng T and Vitale, Susan and American Academy of Ophthalmology Preferred Practice Pattern Refractive Management/Intervention Panel}
}
@article {1532356,
	title = {Infiltrates Versus Ulcers: Why Words Matter},
	journal = {Eye Contact Lens},
	volume = {46},
	number = {5},
	year = {2020},
	month = {2020 Sep},
	pages = {263-264},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000714},
	author = {Jacobs, Deborah S}
}
@article {1586162,
	title = {CLEAR - Medical use of contact lenses},
	journal = {Cont Lens Anterior Eye},
	volume = {44},
	number = {2},
	year = {2021},
	month = {2021 Apr},
	pages = {289-329},
	abstract = {The medical use of contact lenses is a solution for many complex ocular conditions, including high refractive error, irregular astigmatism, primary and secondary corneal ectasia, disfiguring disease, and ocular surface disease. The development of highly oxygen permeable soft and rigid materials has extended the suitability of contact lenses for such applications. There is consistent evidence that bandage soft contact lenses, particularly silicone hydrogel lenses, improve epithelial healing and reduce pain in persistent epithelial defects, after trauma or surgery, and in corneal dystrophies. Drug delivery applications of contact lens hold promise for improving topical therapy. Modern scleral lens practice has achieved great success for both visual rehabilitation and therapeutic applications, including those requiring retention of a tear reservoir or protection from an adverse environment. This report offers a practical and relevant summary of the current evidence for the medical use of contact lenses for all eye care professionals including optometrists, ophthalmologists, opticians, and orthoptists. Topics covered include indications for use in both acute and chronic conditions, lens selection, patient selection, wear and care regimens, and recommended aftercare schedules. Prevention, presentation, and management of complications of medical use are reviewed.},
	issn = {1476-5411},
	doi = {10.1016/j.clae.2021.02.002},
	author = {Jacobs, Deborah S and Carrasquillo, Karen G and Cottrell, Paul D and Fern{\'a}ndez-Vel{\'a}zquez, Fernando J and Gil-Cazorla, Raquel and Jalbert, Isabelle and Pucker, Andrew D and Riccobono, Kellen and Robertson, Danielle M and Szczotka-Flynn, Loretta and Speedwell, Lynne and Stapleton, Fiona}
}
@article {1647907,
	title = {Knowledge},
	journal = {Eye Contact Lens},
	volume = {48},
	number = {7},
	year = {2022},
	month = {2022 Jul 01},
	pages = {277},
	keywords = {Humans, Knowledge},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000918},
	author = {Jacobs, Deborah S}
}
@article {1661819,
	title = {Refractive Surgery Preferred Practice Pattern{\textregistered}},
	journal = {Ophthalmology},
	volume = {130},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {P61-P135},
	keywords = {Humans, Ophthalmology, Practice Patterns, Physicians{\textquoteright}, Refractive Surgical Procedures},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.10.032},
	author = {Jacobs, Deborah S and Lee, Jimmy K and Shen, Tueng T and Afshari, Natalie A and Bishop, Rachel J and Keenan, Jeremy D and Vitale, Susan}
}
@article {1598059,
	title = {Specific Abnormalities in White Matter Pathways as Interface to Small Vessels Disease and Cognition in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Individuals},
	journal = {Brain Connect},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 Feb},
	pages = {52-60},
	abstract = {Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by leukoencephalopathy leading to cognitive impairment. Subtle cognitive deficits can be observed early in the course of the disease, before the occurrence of the first stroke. Therefore, markers that can predict disease progression at this early stage, when interventions are likely to alter disease course, are needed. We aimed to examine the biological cascade of microstructural and macrostructural white matter (WM) abnormalities underlying cognitive deficits in CADASIL. Methods: We examined 20 nondemented CADASIL mutation carriers and 23 noncarriers who underwent neuropsychological evaluation and magnetic resonance imaging. Using probabilistic tractography of key WM tracts, we examined group differences in diffusivity measures and WM hyperintensity volume. Successive mediation models examined whether tract-specific WM abnormalities mediated subtle cognitive differences between CADASIL mutation carriers and noncarriers. Results: The largest effect size differentiating the two groups was observed for left superior longitudinal fasciculus-temporal (SLFt) diffusivity (Cohen{\textquoteright}s f = 0.49). No group differences were observed with a global diffusion measure. These specific microstructural differences in the SLFt were associated with higher WM hyperintensities burden, and subtle executive deficits in CADASIL mutation carriers. Discussion: Worse diffusivity in the left SLFt is related to greater severity of small vessel disease and worse executive functioning in the asymptomatic stage of the disease. Worse diffusivity of the left SLFt may potentially hold promise as an indicator of disease progression. Impact statement Diffusion tensor imaging outperforms conventional imaging of subcortical small vessel disease as a potential marker of future disease progression. Here we identified the left superior longitudinal temporal fasciculus as a critical white matter fiber bundle, of which worse diffusivity can link presence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy mutations to greater severity of small vessel disease and worse executive functioning in asymptomatic stages of the disease. This tract may hold promise and deserves further examination as an early indicator of disease progression.},
	issn = {2158-0022},
	doi = {10.1089/brain.2020.0980},
	author = {Jacobs, Heidi I L and Schoemaker, Dorothee and Torrico-Teave, Hei and Zuluaga, Yesica and Velilla-Jimenez, Lina and Ospina-Villegas, Carolina and Lopera, Francisco and Arboleda-Velasquez, Joseph F and Quiroz, Yakeel T}
}
@article {1549034,
	title = {Is Overnight Orthokeratology OK for Kids?},
	journal = {Eye Contact Lens},
	volume = {47},
	number = {2},
	year = {2021},
	month = {2021 Feb 01},
	pages = {69-70},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000763},
	author = {Jacobs, Deborah S and Jhanji, Vishal}
}
@article {1559541,
	title = {Exclusively endoscopic endonasal resection of benign orbital tumors: a systematic review and meta-analysis},
	journal = {Int Forum Allergy Rhinol},
	volume = {11},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {924-934},
	abstract = {BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) classification system was developed to standardize prospective outcome analysis following orbital cavernous hemangioma (OCH) resection. The goal of this study was to retroactively apply the CHEER system to all prior existing reports of endoscopic resection of primary benign orbital tumors (BOTs) to: (1) compare patient presentations, perioperative characteristics, and outcomes between OCH and other BOTs; and (2) determine whether the CHEER categorization regime could be expanded to other BOTs. METHODS: A systematic review of studies reporting exclusively endoscopic resections of OCH and other BOTs (eg, solitary fibrous tumor, schwannoma, and meningioma) was performed. Patient, tumor characteristics, and operative outcomes were recorded. All tumors with adequate reporting were retrospectively assigned a CHEER stage. Outcomes were compared using chi-square or Fisher{\textquoteright}s exact tests. RESULTS: Ninety-three studies met inclusion criteria, and sufficient data were available in 36 studies, comprising 105 tumors (n = 87 OCHs; n = 18 other BOTs). Baseline patient and tumor characteristics, as well as intraoperative and short-term postoperative outcomes were not significantly different between OCHs and other BOTs. Long-term outcomes (eg, visual deficits, diplopia, eye position, and recurrence) also did not differ when controlling for CHEER stage. CONCLUSION: This review represents the largest collection of outcomes data following exclusively endoscopic endonasal resection of BOTs. Short-term and long-term outcomes appear similar between OCHs and other BOTs. These results suggest that exclusively endoscopic resection of orbital tumors may be effective in a range of benign pathologies. Furthermore, these results support a broader application of the CHEER system to other benign primary orbital tumors.},
	issn = {2042-6984},
	doi = {10.1002/alr.22745},
	author = {Jafari, Aria and von Sneidern, Manuela and Lehmann, Ashton E and Shen, Sarek A and Shishido, Sachie and Freitag, Suzanne K and Bleier, Benjamin S}
}
@article {1538337,
	title = {Radioanatomic Characteristics of the Posteromedial Intraconal Space: Implications for Endoscopic Resection of Orbital Lesions},
	journal = {AJNR Am J Neuroradiol},
	volume = {41},
	number = {12},
	year = {2020},
	month = {2020 12},
	pages = {2327-2332},
	abstract = {BACKGROUND AND PURPOSE: Imaging is essential in the diagnostic work-up of patients with orbital lesions. The position of an orbital lesion relative to the inferomedial muscular trunk of the ophthalmic artery determines endoscopic resectability, anticipated technical difficulty, and patient morbidity. Although the inferomedial muscular trunk is not readily identifiable on preoperative imaging, we hypothesize that it is spatially approximate to the location where the ophthalmic artery crosses the optic nerve. Our aim was to determine whether the ophthalmic artery-optic nerve crosspoint anatomically approximates the inferomedial muscular trunk in a cadaver study and can be appreciated on imaging of known posteromedial orbital lesions. MATERIALS AND METHODS: Dissection was performed on 17 fresh-frozen cadaver orbits to assess the relationship between the inferomedial muscular trunk and ophthalmic artery-optic nerve crosspoint. Retrospective review of imaging in 9 patients with posteromedial orbital lesions assessed posteromedial orbital compartment characteristics and the ability to locate the ophthalmic artery-optic nerve crosspoint. RESULTS: In our cadaver study, the mean distance between the ophthalmic artery-optic nerve crosspoint and the inferomedial muscular trunk was 1.21 {\textpm} 0.64 mm. Retrospectively, the ophthalmic artery-optic nerve crosspoint was identifiable in 9/9 patients, whereas the inferomedial muscular trunk was not identifiable in any patient. Total or partial effacement of the posteromedial intraconal fat triangle was observed in 9/9 patients. CONCLUSIONS: This study of neurovascular relationships within the posteromedial orbit demonstrates that the ophthalmic artery-optic nerve crosspoint closely approximates the inferomedial muscular trunk and can be seen in patients with posteromedial orbital lesions. Posteromedial intraconal fat effacement may help to localize these lesions. These findings may facilitate multidisciplinary communication and help predict lesion resectability and patient outcomes.},
	issn = {1936-959X},
	doi = {10.3174/ajnr.A6822},
	author = {Jafari, A and Lehmann, A E and Wolkow, N and Juliano, A F and Bleier, B S and Reinshagen, K L}
}
@article {1667717,
	title = {Orbital resection by intranasal technique (ORBIT): A new classification system for reporting endoscopically resectable primary benign orbital tumors},
	journal = {Int Forum Allergy Rhinol},
	volume = {13},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {1852-1863},
	abstract = {BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher{\textquoteright}s exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class. RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0\&nbsp;{\textpm}\&nbsp;15.0 years, 51.9\% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p\&nbsp;\&lt;\&nbsp;0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p\&nbsp;\&lt;\&nbsp;0.05). CONCLUSION: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.},
	keywords = {Adult, Endoscopy, Female, Hemangioma, Cavernous, Humans, Male, Middle Aged, Nose, Orbital Neoplasms, Retrospective Studies, Treatment Outcome},
	issn = {2042-6984},
	doi = {10.1002/alr.23141},
	author = {Jafari, Aria and Adappa, Nithin D and Anagnos, Vincent J and Campbell, Raewyn G and Castelnuovo, Paolo and Chalian, Ara and Chambers, Christopher B and Chitguppi, Chandala and Dallan, Iacopo and El Rassi, Edward and Freitag, Suzanne K and Fernandez Miranda, Juan C and Ferreira, Manuel and Gardner, Paul A and Gudis, David A and Harvey, Richard J and Huang, Qian and Humphreys, Ian M and Kennedy, David W and Lee, John Y K and Lehmann, Ashton E and Locatelli, Davide and McKinney, Kibwei A and Moreau, Annie and Nyquist, Gurston and Palmer, James N and Prepageran, Narayanan and Pribitkin, Edmund A and Rabinowitz, Mindy R and Rosen, Marc R and Sacks, Raymond and Sharma, Dhruv and Snyderman, Carl H and Tonya Stefko, S and Stokken, Janalee K and Wang, Eric W and Workman, Alan D and Wu, Arthur W and Yu, Jen Y and Zhang, Matthew M and Zhou, Bing and Bleier, Benjamin S}
}
@article {1435404,
	title = {Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Chronic Noninfectious Uveitis Affecting the Posterior Segment: Twelve-Month Results},
	journal = {Ophthalmology},
	volume = {126},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {601-610},
	abstract = {PURPOSE: To assess the safety and efficacy of an intravitreal fluocinolone acetonide (FA) insert to manage inflammation associated with chronic noninfectious posterior uveitis. DESIGN: Multicenter, randomized, prospective, doubled-masked, sham-controlled, 3-year phase 3 clinical trial. PARTICIPANTS: One hundred twenty-nine participants with recurrent noninfectious posterior uveitis were assigned randomly to FA insert (n\&nbsp;= 87) or sham injection (n\&nbsp;= 42). The more severely affected eye in participants with bilateral disease was designated as the study eye. METHODS: The insert (FA, 0.18 mg) was injected into the vitreous cavity; sham injection mimicked the insert delivery procedure. Ophthalmic examinations, OCT, and ocular tolerability and discomfort assessments were conducted; study visits were on days 7 and 28 and months 2, 3, 6, 9, and 12. Uveitis recurrence was treated as needed. The 6-month recurrence rate was the primary outcome measure. RESULTS: The 6-month (28\% and 91\%) and 12-month (38\% and 98\%) uveitis recurrence rates were significantly lower (P \&lt; 0.001) with FA insert vs. sham, respectively. Fewer recurrences per study eye (mean, 0.7 vs. 2.5), lower incidence of 15-letter or more decrease in best-corrected visual acuity (14\% vs. 31\%), and reduced systemic (19\% vs. 40\%) and local (7\% vs. 62\%) uveitis adjunctive treatments were observed with FA insert vs. sham, respectively. The FA insert group showed higher rates of cataract. Intraocular pressure-lowering treatment use was similar between groups. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. CONCLUSIONS: Chronic noninfectious posterior uveitis was managed successfully in this study population; FA insert eyes experienced fewer uveitis recurrence episodes, required fewer adjunctive treatments, and demonstrated less visual acuity loss compared with sham eyes. The FA insert treatment group showed higher rates of cataract; delivery by injection was not associated with an increase in ocular adverse events or any other safety measures not typically associated with local steroid use, suggesting the procedure is appropriate for an office\&nbsp;setting.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.10.033},
	author = {Jaffe, Glenn J and Foster, C Stephen and Pavesio, Carlos E and Paggiarino, Dario A and Riedel, Gerard E}
}
@article {591281,
	title = {A Phase 1 Study of Intravitreous E10030 in Combination with Ranibizumab in Neovascular Age-Related Macular Degeneration.},
	journal = {Ophthalmology},
	volume = {123},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {78-85},
	abstract = {PURPOSE: To assess the safety and tolerability of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, when administered in combination with an anti-vascular endothelial growth factor (VEGF) agent, ranibizumab (Lucentis; Genentech, South San Francisco, CA) 0.5 mg, by intravitreal injection in participants with neovascular age-related macular degeneration (NVAMD). DESIGN: Prospective phase 1 clinical trial. PARTICIPANTS: A total of 23 participants diagnosed with NVAMD and aged 50 years or older were enrolled. METHODS: Part 1 included 15 participants. Three participants received a single intravitreal E10030 (0.03 mg) injection and were subsequently given intravitreal ranibizumab (0.5 mg) injections at weeks 2, 6, and 10. Twelve participants (3 per group) received E10030 (0.03, 0.3, 1.5, or 3.0 mg) in combination with ranibizumab (0.5 mg) at day 0, month 1, and month 2 in an ascending manner. In Part 2 (8 participants), E10030 (0.3, 1.5, or 3.0 mg) in combination with ranibizumab (0.5 mg) was injected at day 0, month 1, and month\&nbsp;2. MAIN OUTCOME MEASURES: Safety at week 12 was the primary outcome and included assessment of vital signs, laboratory tests, and serial eye examinations. Other safety metrics included assessment through week 24 of Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) and biomarker changes evaluated by optical coherence tomography (OCT) and fluorescein angiography (FA). RESULTS: All doses of intravitreal E10030 administered in combination with ranibizumab were well tolerated. No dose-limiting toxicities or relevant safety events were noted at any dose level during the study. Investigators did not report adverse events related to E10030 or ranibizumab. Mean VA change was a gain of 14 letters, and 59\% of participants gained >=15 letters from baseline at week 12. On FA at week 12, there was an 85.5\% mean reduction from baseline in choroidal neovascularization (CNV) size. On OCT at the week 12 visit, there was a mean decrease in center point thickness and central subfield thickness of 38.9\% and 33.7\%, respectively. CONCLUSIONS: Intravitreal E10030 administered at doses up to 3 mg in combination with ranibizumab was well tolerated without evidence of systemic or ocular toxicity in participants with NVAMD. The changes in both mean VA and imaging biomarkers suggest a favorable short-term safety profile for the combination therapy of E10030 and ranibizumab.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.09.004},
	author = {Jaffe, Glenn J and Eliott, Dean and Wells, John A and Prenner, Jonathan L and Papp, Andras and Patel, Samir}
}
@article {1559574,
	title = {Eye Diseases Direct Interest to Complement Pathway and Macrophages as Regulators of Inflammation in COVID-19},
	journal = {Asia Pac J Ophthalmol (Phila)},
	year = {2020},
	month = {2020 Dec 07},
	abstract = {Many of the risk factors for developing severe coronavirus disease 2019 (COVID-19) are also risk factors for eye diseases such as age-related macular degeneration (AMD). During the past decades, macrophages and the complement pathway (as a part of the innate immune system) have been identified as important contributors to the development of AMD, and we suggest that these mechanisms are of similar importance for the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Based on the experience with AMD, we discuss how behavioral factors such as diet, smoking and higher body mass index, as well as genetic determinants such as the complement and immune pathway genes may lead to the overactive inflammatory phenotypes seen in some patients with COVID-19, and may in part explain the heterogeneity of disease manifestations and outcomes. Based on this experience, we discuss potential genetic research projects and elaborate on preventive and treatment approaches related to COVID-19.},
	issn = {2162-0989},
	doi = {10.1097/APO.0000000000000346},
	author = {Jager, Martine J and Seddon, Johanna M}
}
@article {931091,
	title = {Reply: amniotic membrane transplantation in Stevens-Johnson syndrome},
	journal = {Surv Ophthalmol},
	volume = {62},
	number = {2},
	year = {2017},
	month = {2017 Mar - Apr},
	pages = {249-250},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.10.005},
	author = {Jain, Rajat and Sharma, Namrata and Basu, Sayan and Iyer, Geetha and Ueta, Mayumi and Sotozono, Chie and Kannibiran, Chitra and Rathi, Varsha M and Gupta, Nidhi and Kinoshita, Shigeru and Gomes, Jos{\'e} A P and Chodosh, James and Sangwan, Virender S}
}
@article {836876,
	title = {Stevens-Johnson syndrome: The role of an ophthalmologist.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {4},
	year = {2016},
	month = {2016 Jul-Aug},
	pages = {369-99},
	abstract = {Stevens-Johnson syndrome (SJS) is an acute blistering disease of the skin and mucous membranes. Acute SJS leads to the acute inflammation of the ocular surface and chronic conjunctivitis. If not properly treated, it causes chronic cicatricial conjunctivitis and cicatricial lid margin abnormalities. Persistent inflammation and ulceration of the ocular surface with cicatricial complications of the lids leads to chronic ocular sequelae, ocular surface damage, and corneal scarring. The destruction of the glands that secrete the tear film leads to a severe form of dry eye that makes the management of chronic SJS difficult. The option that is routinely used for corneal visual rehabilitation, keratoplasty, is best avoided in such cases. We describe the management strategies that are most effective during the acute and chronic stages of SJS. Although treatments for acute SJS involve immunosuppressive and immunomodulatory therapies, amniotic membrane transplantation is also useful. The options for visual rehabilitation in patients with chronic SJS are undergoing radical change. We describe the existing literature regarding the management of SJS and highlight recent advances in the management of this disorder.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.01.004},
	author = {Jain, Rajat and Sharma, Namrata and Basu, Sayan and Iyer, Geetha and Ueta, Mayumi and Sotozono, Chie and Kannabiran, Chitra and Rathi, Varsha M and Gupta, Nidhi and Kinoshita, Shigeru and Gomes, Jos{\'e} A P and Chodosh, James and Sangwan, Virender S}
}
@article {303851,
	title = {Massive retinal gliosis in neurofibromatosis type 1.},
	journal = {JAMA Ophthalmol},
	year = {2014},
	month = {2014 Oct 9},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.3958},
	author = {Jakobiec, Frederick A and Rashid, Alia and Lewis, Kyle}
}
@article {705081,
	title = {So-called massive retinal gliosis: A critical review and reappraisal.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {3},
	year = {2016},
	month = {2016 May-Jun},
	pages = {339-56},
	abstract = {Massive retinal gliosis, a nonneoplastic retinal glial proliferation, was first described in detail over 25\&nbsp;years ago, before the era of immunohistochemistry, in a series of 38 cases-to which can be added 30 case reports or small series (no more than 3 cases) subsequently. We analyze a new series of 3 nontumoral intraretinal glioses and 15 cases of tumoral retinal gliosis, not all of which, strictly speaking, were massive. The data from this series are compared with the findings in previously published cases. Included are 2 cases of massive retinal gliosis diagnosed from evisceration specimens. In reviewing all published and current cases, we were able to establish 3 subgroups of retinal tumoral glioses rather than a single "massive" category: focal nodular gliosis, submassive gliosis, and massive gliosis. Among 43 reported cases, including the present series, but excluding the previous large series of 38 cases in which substantial clinical data were omitted, there were 19 men and 24 women. Their mean and median ages were 36.2\&nbsp;years and 36\&nbsp;years, respectively, with a range of 2 to 79\&nbsp;years. All lesions were composed of mitotically quiet, compact spindled fibrous astrocytes devoid of an Alcian blue-positive myxoid matrix. The most common associated ocular conditions were phthisis bulbi and congenital diseases or malformations. Histopathologically, all 3 tumoral categories were accompanied by progressively more extensive fibrous and osseous metaplasia of the pigment epithelium, the latter forming a clinically and diagnostically useful, almost continuous, outer rim of eggshell calcification in the submassive and massive categories that should be detectable with appropriate imaging studies. In decreasing order of frequency, microcysts and macrocysts, vascular sclerosis, exudates, calcospherites, and Rosenthal fibers were observed among the proliferating fibrous astrocytes. Immunohistochemistry was positive for glial fibrillary acidic protein in all cases and nestin in most (an intermediate cytoplasmic filament typically restricted to embryonic and reparative neural tissue). The nonneoplastic nature of all categories of gliosis was confirmed by absent TP53 (tumor suppressor gene) dysregulation, Ki-67 negativity, and intact p16 expression (the protein product of the p16 tumor suppressor gene) in the overwhelming majority of cases. These findings indicate an intrinsic attempt to regulate and maintain a low level of glial cell proliferation that becomes unsuccessful as the disease evolves. The categories of tumoral proliferation appeared to constitute a spectrum. We conclude that focal nodular tumors encompass lesions previously called retinal vasoproliferative lesions, which display the same histopathologic and immunohistochemical findings as 3 major categories of retinal gliosis characterized herein.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2015.12.002},
	author = {Jakobiec, Frederick A and Thanos, Aristomenis and Stagner, Anna M and Grossniklaus, Hans E and Proia, Alan D}
}
@article {961721,
	title = {Dermatofibroma of the eyelid with monster cells},
	journal = {Surv Ophthalmol},
	volume = {62},
	number = {4},
	year = {2017},
	month = {2017 Jul - Aug},
	pages = {533-540},
	abstract = {Dermatofibromas are most frequently encountered in women on the lower extremities, often after minor trauma. A recurrent lesion of the right lower eyelid developed in a 64-year-old woman. It harbored "monster cells" that were large, with either multiple nuclei or a single, large, convoluted, and hyperchromatic nucleus. The presence of these cells does not signify a malignant transformation. The background cells were either histiocytoid (many were adipophilin positive), spindled cells, or dendritiform cells without mitoses. Factor XIIIa, CD68, and CD163 immunostaining was positive, and a subpopulation of CD1a(+) Langerhans cells was intermixed. Facial and eyelid dermatofibromas are more likely to recur and deserve wider, tumor-free surgical margins. Their microscopic differential diagnosis includes a cellular scar, peripheral nerve tumor, atypical fibrous xanthoma, and dermatofibrosarcoma protuberans.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.12.007},
	author = {Jakobiec, Frederick A and Tu, Yufei and Zakka, Fouad R and Tong, Arthur K F}
}
@article {1354353,
	title = {An analysis of conjunctival and periocular venous malformations: clinicopathologic and immunohistochemical features with a comparison of racemose and cirsoid lesions},
	journal = {Surv Ophthalmol},
	volume = {59},
	number = {2},
	year = {2014},
	month = {2014 Mar-Apr},
	pages = {236-44},
	abstract = {Vascular tumors (in contrast to dilations or ectasias) of the conjunctiva and other adnexal tissues are rare, with no previous convincing example of a congenital, purely venous conjunctival malformation having been described. A 33-year-old man with a previously well-tolerated racemose conjunctival lesion present from birth developed bothersome symptoms when it underwent multifocal thrombosis with papillary endothelial cell hyperplasia as part of the process of thrombotic organization. Conservative subtotal excision with placement of an amniotic graft led to an acceptable cosmetic appearance, abatement of symptoms, and retention of full ocular function. Histopathologically, the lesion was composed of patulous vascular channels with thin walls displaying a negligible and irregular muscularis, diffuse supportive mural fibrosis, and the absence of an elastic lamina. Immunohistochemically the endothelial cells were CD31- and CD34-positive (vascular origin) but D2-40-negative (lymphatic origin). An associated neovascular capillary bed was not detected. Venous (racemose or grape-like) malformations should be distinguished from: arteriovenous (cirsoid or twisted) malformations in which the vessels possess thicker and more uniform muscular walls, some of which are endowed with an elastica; varices (hemorrhoidal dilations typically of a pre-existent vein); and venous angiomas (noncongenital lesions acquired in middle life) composed of regularly structured muscular channels devoid of an elastic lamina. Other conditions not to be confused with congenital venous malformations include hemorrhagic lymphangiectasia (of Leber), hemorrhagic lymphangiomas, and complex lymphaticovenous malformations.},
	keywords = {Adult, Conjunctival Neoplasms, Eye Neoplasms, Humans, Male, Vascular Malformations},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2013.06.003},
	author = {Jakobiec, Frederick A and Werdich, Xiang Q and Chodosh, James and Freitag, Suzanne K}
}
@article {541321,
	title = {Bilateral Eyelid Pseudoptosis From Lipogranulomas of the Preaponeurotic Fat Pads.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {5},
	year = {2015},
	month = {2015 Sep-Oct},
	pages = {e125-31},
	abstract = {Lipogranulomas of the periocular tissues with fulminant fibrotic and lymphohistiocytic responses were initially described in cases of exogenous paraffin or petrolatum jelly injections ("paraffinomas"). A 49-year-old Cambodian woman slowly developed bilateral pseudoptosis with intact levator function and redundant, taut upper eyelid skin. At surgery, vesiculations or "bubbles" in the preaponeurotic fat were encountered and were demonstrated histopathologically to be empty locules surrounded by a thin collagenous lamina. Outside these extracellular spaces were CD68/CD163-positive mononucleated and univacuolated histiocytes simulating damaged fat cells or neoplastic lipoblasts in hematoxylin and eosin sections. Giant cells and chronic sclerosing inflammation were absent. The patient denied any previous injections. The bland character of the lipogranulomas in comparison with that of other injectable agents, the absence of any residual particles associated with other cosmetic fillers, and the distinctive histiocytic response of lipoblast-like cells that were sufficiently characteristic to compel the diagnosis of surreptitious silicone injections. Other conditions were excluded based on comparative clinicopathologic criteria.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000157},
	author = {Jakobiec, Frederick A and Rai, Ruju and Rashid, Alia and Sutula, Francis C}
}
@article {882951,
	title = {Unusual pleomorphic adenoma of the lacrimal Gland: Immunohistochemical demonstration of PLAG1 and HMGA2 oncoproteins},
	journal = {Surv Ophthalmol},
	volume = {62},
	number = {2},
	year = {2017},
	month = {2017 Mar - Apr},
	pages = {219-226},
	abstract = {Painless low-grade right proptosis with 20/25 visual acuity developed slowly in a 49-year-old woman with a past history of breast cancer. Imaging studies disclosed an oval-to-round superotemporal mass in the right lacrimal fossa without bone erosion. Excisional biopsy revealed a pseudoencapsulated, bosselated tumor with a spindled, hypocellular, and heavily periodic acid Schiff-positive stroma constituted of abundant basement membrane material and collagen. Scattered lumens and focal cribriform cellular clusters were present in the peripheries of several of the lobules. Immunohistochemistry showed epithelial membrane antigen+ and cytokeratin (CK) 7+ in many small luminal structures. The spindled cells were calponin+, CK5/6+, CK14+, and p63+, confirming their myoepithelial nature. The Ki67 proliferation index was 2-3\%, and upregulation of nuclear p53, a tumor suppressor gene product which may be aberrantly overexpressed in malignancy, was observed in rare cells. Immunohistochemical probes for HMGA2 and PLAG1 oncoproteins, characteristic of pleomorphic adenoma, were stained intensely and less intensely, respectively. MYB and c-KIT (CD117) were negative, thereby strongly arguing against the diagnosis of adenoid cystic carcinoma. In atypical epithelial tumors of the lacrimal gland, genetic probes identifying distinctive gene translocations or their oncoprotein products complement traditional immunohistochemical biomarkers such as cytokeratins and other structural or secretory molecules. Characteristic genetic abnormalities demonstrated by immunohistochemistry for their upregulated protein products, or by in situ hybridization for translocations, are increasingly being relied on for diagnostic precision.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.08.001},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Eagle, Ralph C and Lally, Sara E and Krane, Jeffrey F}
}
@article {655086,
	title = {A microanatomic abnormality of the lacrimal gland associated with Goldenhar syndrome.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {5},
	year = {2016},
	month = {2016 Sep-Oct},
	pages = {654-63},
	abstract = {A 12-month-old male infant, noted from birth to have a diffuse right temporal epibulbar thickening that encroached on the limbus inferotemporally, was found to manifest stigmata of Goldenhar syndrome, including a limbal dermoid with vellus hairs, esotropia, astigmatism, fullness and ectropion of the lower eyelid, preauricular skin tag, agenesis of the right kidney, and a supernumerary rib. In the excised epibulbar specimen, in addition to a solid dermoid, lobules of lacrimal gland tissue were interpreted as a portion of the palpebral or orbital lobes. This tissue displayed a unique histopathologic finding. Within some of the lobules were cuffs of eosinophilic squamous (epidermoid) cells that surrounded the intralobular ductules and made variable incursions into, with replacement of, the acinar units. Immunohistochemistry disclosed that the normal acinar and lumen-forming ductular cells were intermediate weight cytokeratin7-positive. The acinar cells were additionally gross cystic disease fluid protein-15 positive. The cells of the squamous cuffs were heavy weight cytokeratin 5/6-positive. The outermost basal cells of the cuffs were cytokeratin 14-positive, in common with the myoepithelial cells of the acini. The\&nbsp;intraacinar squamous cells were negative for smooth muscle actin and gross cystic disease fluid protein-15. These findings suggest, but do not prove, that the source of the periductular and acinar squamous metaplasia was the germinal transitional cells where the acinar myoepithelium interfaces and imperceptibly converts into ductular basal cells. The foregoing findings are evaluated in the context of the panoply of ocular, facial, and visceral anomalies manifested in Goldenhar spectrum.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.02.002},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Katowitz, William R and Eagle, Ralph C}
}
@article {280811,
	title = {Immunohistochemical investigations of adult intraocular medulloepitheliomas.},
	journal = {Clin Experiment Ophthalmol},
	year = {2014},
	month = {2014 Sep 23},
	issn = {1442-9071},
	doi = {10.1111/ceo.12436},
	author = {Jakobiec, Frederick A and Rose, Matthew F and Trief, Danielle and Stagner, Anna M and Kim, Ivana and Gragoudas, Evangelos S}
}
@article {314141,
	title = {New insights into the development of infantile intraocular medulloepithelioma.},
	journal = {Am J Ophthalmol},
	volume = {158},
	number = {6},
	year = {2014},
	month = {2014 Dec},
	pages = {1275-1296.e1},
	abstract = {PURPOSE: To define the maturational sequence of 3 infantile intraocular medulloepitheliomas. DESIGN: Retrospective clinicohistopathologic and immunohistochemical study. METHODS: Immunoreactivity of paraffin sections for CRX (cone-rod homebox transcription factor) and NeuN (biomarker for neuronal differentiation) were investigated together with other biomarkers, including S100, glial fibrillary acidic protein, epithelial membrane antigen, and various cytokeratins. RESULTS: Three infants (aged 1, 6, and 8\&nbsp;months) had iris neovascularization, 2 had anterior ciliary body tumors, and 1 a posterior tumor associated with a retinochoroidal coloboma. Each tumor displayed a premedullary monolayer of cuboidal epithelium that was S100(+), NeuN(-), and CRX(-) and that transitioned into a multilaminar medullary epithelium forming neurotubules with adluminal cells that were CRX(+). NeuN first appeared in ablumenal neurotubular cells in 1 tumor and was also discovered among neuroblast-appearing cells in another. The third tumor associated with a coloboma was CRX(-) and NeuN(-). CONCLUSIONS: A simple premedullary epithelial monolayer appears to be the fundamental source for the tumor and its multilaminar medullary epithelium. CRX(+) and NeuN(+) cells within the multilayered medullary layer approximate expression patterns similar to those found in retinal development and differentiation. Discovery of these biomarkers in the neoplastic ciliary epithelium in a small number of tumors indicates preliminarily that the most anterior layers of the optic cup have a retained retinal and neuroglial differentiation potentiality. The third case was CRX(-) and NeuN(-) and possibly arose from embryonic pigment epithelium at the edge of the retinochoroidal coloboma. These immunohistochemical findings offer histogenetic and potential diagnostic insights.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.08.036},
	author = {Jakobiec, Frederick A and Trief, Danielle and Rashid, Alia and Rose, Matthew F and Minckler, Don and Vanderveen, Deborah and Mukai, Shizuo}
}
@article {1363126,
	title = {The cytologic composition of dacryops: an immunohistochemical investigation of 15 lesions compared to the normal lacrimal gland},
	journal = {Am J Ophthalmol},
	volume = {155},
	number = {2},
	year = {2013},
	month = {2013 Feb},
	pages = {380-396.e1},
	abstract = {PURPOSE: To define the cytologic composition of the double-layered epithelial lining of dacryops (lacrimal duct cyst), improve histopathologic diagnosis, and better understand pathogenesis. DESIGN: Clinicopathologic retrospective study with immunohistochemical studies of 15 lesions compared with normal lacrimal gland. METHODS: Clinical data from 14 patients were reviewed and microscopy was performed with routine stains and immunohistochemical probes for epithelial membrane antigen (EMA), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7), and smooth muscle actin (SMA). RESULTS: The major lacrimal gland was involved in 13 lesions; 2 lesions arose in an accessory gland of Krause. One case was bilateral; the average age of the patients was 50.7 years. Neither visual acuity nor motility was disturbed. No lesion was discovered to have recurred after excision. Microscopically, in all dacryops specimens goblet cells and luminal pseudoapocrine apical cytoplasmic projections were identified. Lacrimal acinar cells immunoreacted with GCDFP-15 and CK7, whereas the normal ducts and the epithelium of the dacryops lesions reacted diffusely only with CK7. SMA-positive myoepithelial cells were found in the acini but not in the normal ducts or dacryops epithelium. CONCLUSIONS: Negative GCDFP-15 staining ruled out apocrine metaplasia in dacryops. Normal ducts and dacryops showed no immunohistochemical evidence for the presence of myoepithelial cells. Pathogenetic theories of dacryops that implicate a failure of ductular "neuromuscular" contractility must therefore be revised. A dysfunction of the rich neural plexus around the ductules may play a role in the development of dacryops in conjunction with periductular inflammation and induced scarring.},
	keywords = {Actins, Adult, Aged, Biomarkers, Carrier Proteins, Child, Preschool, Cysts, Female, Glycoproteins, Humans, Immunoenzyme Techniques, Keratin-7, Lacrimal Apparatus, Lacrimal Apparatus Diseases, Magnetic Resonance Imaging, Male, Middle Aged, Mucin-1, Retrospective Studies, Tomography, X-Ray Computed},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2012.07.028},
	author = {Jakobiec, Frederick A and Zakka, Fouad R and Perry, Lynn P}
}
@article {503906,
	title = {Histopathologic Clues in Diagnosing Oral Mucosal Grafts to the Conjunctiva.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 Jul 31},
	abstract = {Excised redundant, forniceal "conjunctival" tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000534},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Raizman, Michael B and Hatton, Mark P}
}
@article {1364619,
	title = {Angiomyofibroma of the orbit: a hybrid of vascular leiomyoma and cavernous hemangioma},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {28},
	number = {6},
	year = {2012},
	month = {2012 Nov-Dec},
	pages = {438-45},
	abstract = {PURPOSE: The aim of this study was to describe a novel primary orbital vascular tumor combining elements of a vascular leiomyoma (angioleiomyoma) and a cavernous hemangioma. METHODS: A critical review of clinical records, diagnostic tests, and radiographic studies combined with histopathologic evaluation with standard and special histochemical staining and immunohistochemical investigations was conducted. RESULTS: A 44-year-old man slowly developed 5 mm of well-tolerated relative right proptosis with minimal motility disturbance and no visual decline. Computed tomography and magnetic resonance imaging demonstrated a medial and intraconal rounded mass that perfused slowly and whose anterior surface was well circumscribed. At surgery, the tumor was solid and pink with intersecting white bands and densely attached to surrounding normal tissues. The most adherent apical portion of the mass was left behind after subtotal excision. Histopathologically, only a partial pseudocapsule was discovered. The tumor was composed of cavernous channels, capillary zones, compressed lumens with linear strands of endothelium, and collections of muscular veins devoid of an elastica. Striking smooth muscle actin positivity was identified in disorganized masses of smooth muscle cells in the intervascular spaces and around the cavernous vascular units; these myocytes were intermixed with bundles of interstitial keloidal collagen. The endothelium was CD31 and CD34 positive for vascular endothelium and D2-40 negative for lymphatic endothelium. CONCLUSIONS: The authors have classified this hybrid tumor an angiomyofibroma with low neoplastic potential and features of a malformation. It is a composite variant of cavernous hemangioma associated with a conspicuous proliferation of anomalous disorganized smooth muscle cells (leiomyoma). Most of the lesion lacked a pseudocapsule, which impeded surgical delivery. Incomplete excision is recommended in such cases as preferable to the complications that could ensue from overly aggressive efforts at complete removal, particularly at the orbital apex. Supporting this position is the observation that incompletely excised cavernous hemangioma generally does not recur.},
	keywords = {Actins, Adult, Angiomyoma, Antigens, CD34, Biomarkers, Tumor, Hemangioma, Cavernous, Humans, Male, Orbital Neoplasms, Platelet Endothelial Cell Adhesion Molecule-1, Tomography, X-Ray Computed, Vimentin},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e318269693e},
	author = {Jakobiec, Frederick A and Zakka, Fouad R and Papakostas, Thanos D and Fay, Aaron}
}
@article {742251,
	title = {Intraocular Teratoid Medulloepithelioma Presenting With a Completely Rhabdomyosarcomatous Distant Metastasis.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {8},
	year = {2016},
	month = {2016 Aug 1},
	pages = {919-923},
	abstract = {Importance: Medulloepithelioma is the second most common primary neuroepithelial tumor of the eye. The full range of its morphologic expressions and appearances in metastases have not been fully explored. Observations: A patient in her 50s with glaucoma for decades had undergone multiple filtering surgical procedures, including the placement of a glaucoma drainage device. A paraspinal mass was discovered, and tumor and bone marrow biopsies disclosed rhabdomyosarcoma. This led to the discovery of a multicystic intraocular tumor. A metastatic rhabdomyosarcoma to the eye was considered unlikely because, to our knowledge, this event had never been reported. An enucleation was performed, and an intraocular tumor composed almost entirely of rhabdomyoblasts (desmin- and myogenin-positive) was discovered along with rare clusters of persistent neuroepithelial cells. Conclusions and Relevance: To our knowledge, this is the first case of a medulloepithelioma in which teratoid rhabdomyoblasts effaced all but trace amounts of neuroepithelium and generated a distant metastasis entirely composed of rhabdomyoblasts. The prolonged history and filtering procedures probably led to these 2 phenomena.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.1515},
	author = {Jakobiec, Frederick A and Borkar, Durga S and Stagner, Anna M and Lee, Nahyoung Grace}
}
@article {1573122,
	title = {Epibulbar Proliferative Fasciitis, a Variant of Nodular Fasciitis: A Differential Diagnosis of Conditions With Focal or Diffuse Myxoid Stromas},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2021},
	month = {2021 Jan 19},
	abstract = {PURPOSE: To describe the clinical and pathologic features of a case of epibulbar proliferative fasciitis and to compare it with other focal or diffuse myxoid lesions. METHODS: A clinical, histopathologic, and immunohistochemical analysis was performed. The clinical history, photographic documentation, history, and referred slides were reanalyzed. Additional immunohistochemical stains were performed at our institution. RESULTS: A 68-year-old woman developed over a week a brightly vascularized and focally hemorrhagic placoid lesion on the temporal side of the OS. She had had earlier augmentation breast surgery that had been mistakenly initially reported to us to be for breast carcinoma. Hematoxylin- and eosin-stained reactions revealed microscopically a spindle cell lesion with an intact nonkeratinizing epithelium and a background myxoid stroma with prominent capillaries and a light dispersion of small T-cell lymphocytes. Most striking among the spindle cells were some widely separated large atypical cells. The atypical cells were cytokeratin positive, but an expansive panel of immunohistochemical stains for breast carcinoma was negative. The lesion was diagnosed as proliferative fasciitis and has not recurred after 1-year follow up. CONCLUSION: A rapidly evolving conjunctival lesion is unlikely to be a primary or metastatic carcinoma. In the current case, the large ganglioform or rhabdomyoblast-like cells displayed diffuse cytokeratin positivity, still consistent with a mesenchymal or connective tissue cell lineage. Cytokeratin expression has been a finding previously reported in connective tissue tumors and in lymphoma cells. While the current lesion clinically resembles a conventional nodular fasciitis, the presence of the large atypical cells can lead to the misdiagnosis of a sarcoma, which typically displays a much higher Ki-67 proliferation index in comparison with nodular/proliferative fasciitis.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001872},
	author = {Jakobiec, Frederick A and Barrantes, Paula Cortes and Ma, Lina and Mihm, Martin}
}
@article {987976,
	title = {Unsuspected Conjunctival Orbital Dermoid Cyst: Aids in Diagnosis},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {5},
	year = {2017},
	month = {2017 Sep/Oct},
	pages = {e123-e126},
	abstract = {A 25-year-old man with Type 1 diabetes mellitus experienced rapid visual decline and was scheduled for right cataract surgery. At the time of administering an inferotemporal retrobulbar block, a white discharge appeared spontaneously on the surface of the globe. Superotemporally a cyst was found and its contents were subtotally evacuated. Microscopically, eosinophilic, acellular material with chatter artifact and small vacuoles was detected and initially thought to represent a lens choristoma. This material stained moderately with the periodic acid Schiff method and was focally Congo red positive without apple green birefringence; it also stained blue with the Masson trichrome method. Acid-fast staining disclosed the presence of rare vellous hairs. Adherent cells were not epidermal cells (CK5/6) but conjunctival epithelial cells (CK7); CD68-positive histiocytes were also identified. The lesion was diagnosed as a disrupted orbital dermoid cyst of conjunctival origin.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000851},
	author = {Jakobiec, Frederick A and Zakka, Fouad R and Lorch, Alice}
}
@article {382586,
	title = {Malignant rhabdoid transformation of a longstanding, aggressive, and recurrent orbital angiomyxoma.},
	journal = {Surv Ophthalmol},
	volume = {60},
	number = {2},
	year = {2015},
	month = {2015 Mar-Apr},
	pages = {166-76},
	abstract = {A 47-year-old woman presented with a medial orbital tumor initially diagnosed as either a myxoid neurofibroma or myoepithelioma. Over 30 years the tumor recurred seven times and was serially debulked. Careful histopathologic analysis coupled with immunohistochemical studies performed on the last two biopsies established the rare diagnosis of a locally aggressive angiomyxoma (because of its local infiltrative growth) with myofibroblastic features (smooth muscle actin and calponin positivity and desmin negativity). The last recurrence manifested at a shorter interval than the earlier ones, suggesting an accelerating clinical course. By this late stage there was complete blindness, a frozen globe, and extreme, unmeasurable proptosis accompanied by massive chemosis and eyelid fullness. An exenteration was performed, and the orbital contents contained a persistent angiomyxoma, but additionally, another cellular population had emerged-mitotically active cells with a malignant rhabdoid phenotype (round shape, cytoplasmic hyaline/globoid inclusions composed of whorls of compact vimentin filaments as well as epithelial membrane antigen and focal cytokeratin positivity). This is the first orbital case of a rhabdoid transformation of a benign orbital mesenchymal tumor. Shortly after the exenteration, multifocal metastases, notably to the lungs, were found, leading to the introduction of chemotherapy, which was discontinued because of non-responsiveness of the tumor and patient intolerance. After 1 year of follow up, the patient is still alive, but has persistent active disease with widespread metastases and a guarded prognosis.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2014.12.002},
	author = {Jakobiec, Frederick A and Callahan, Alison B and Stagner, Anna M and Lee, N Grace and Rashid, Alia and Mendoza, Pia and Grove, Arthur and Freitag, Suzanne K}
}
@article {1354354,
	title = {Hyperplastic corneal pannus: an immunohistochemical analysis and review},
	journal = {Surv Ophthalmol},
	volume = {59},
	number = {4},
	year = {2014},
	month = {2014 Jul-Aug},
	pages = {448-53},
	abstract = {An exuberant corneal pannus usually develops in adults with a history of surgery or trauma in the anterior central stroma and appears as a glistening, vascularized, moderately elevated, well circumscribed white nodule. We describe a 78-year-old woman with such a pannus, which in the past has typically been referred to as keloidal or hypertrophic. The involved eye had only light perception, and she underwent a penetrating keratoplasty that improved her vision to 20/100. Histopathologic and immunohistochemical evaluations of a the specimen disclosed a reactive spindle cell stromal proliferation of myofibroblasts that were smooth muscle actin positive with a low Ki67 proliferation index. Desmin, caldesmon, and calponin were negative, in keeping with the incomplete myofilamentary differentiation of a myofibroblast. There was a generous admixture of CD68/163-positive histiocytes and dispersed C3/5-positive T-lymphocytes. An absence of CD138- and IgG4-positive plasma cells ruled out an IgG4-related disease. For a lesion to be keloidal, the collagen must have a thick hyaline character, sharp edges, and a sparsity of intervening cells and vessels. A hypertrophic pannus would be composed of large swollen cells not necessarily increased in number. We therefore recommend adoption of the term hyperplastic for lesions like that described here because of the obvious increase in cellularity from proliferating myofibroblasts and the lack of true keloidal collagen.},
	keywords = {Aged, Biomarkers, Cornea, Female, Histiocytes, Humans, Hyperplasia, Immunohistochemistry, Keloid, Keratoplasty, Penetrating, Myofibroblasts},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2013.10.005},
	author = {Jakobiec, Frederick A and Stacy, Rebecca C and Mendoza, Pia R and Chodosh, James}
}
@article {369081,
	title = {Orbital Conjunctival Cyst Associated With the Superior Rectus-Levator Muscles: A Clinicopathologic Study.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {1},
	year = {2017},
	pages = {e1-e4},
	abstract = {A 55-year-old woman had a right orbital cyst detected incidentally on radiographic imaging. The patient{\textquoteright}s symptoms were mild and included intermittent pain and vertical diplopia; the patient was not aware of any visual decline. There was a palpable mass beneath the superior orbital rim. Radiographic imaging revealed a well-demarcated cystic lesion in the right superior orbit between the levator palpebrae superioris and superior rectus muscles. The mass was completely excised via a transconjunctival approach. Histopathologic evaluation disclosed a conjunctival cyst lined by nonkeratinized squamous epithelium with scattered, rare goblet cells. This case combined with 5 other similar reported cases suggests that an intermuscular cyst located in the superior rectus-levator complex is most likely of congenital embryonic conjunctival origin.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000358},
	author = {Jakobiec, Frederick A and Grob, Seanna R and Stagner, Anna M and Curtin, Hugh and Massoud, Vicky and Fay, Aaron}
}
@article {1302194,
	title = {Osseous and Adipocytic Differentiations in the Intraocular Lens and Vitreous},
	journal = {Am J Ophthalmol},
	volume = {186},
	year = {2018},
	month = {2018 Feb},
	pages = {77-88},
	abstract = {PURPOSE: To analyze 3 unusual mesenchymal transformations within the eye: adipose or osseous metaplasia of the lens and adipose tissue in the vitreous cavity. DESIGN: Observational case series. METHODS: Reevaluation of clinicopathologic diagnoses and histopathologic findings in sections stained with hematoxylin-eosin, periodic acid-Schiff (PAS) reaction, and Masson trichrome method. RESULTS: The 3 cases of mesenchymal transformation occurred in microphthalmic eyes with persistent hyperplastic primary vitreous (more recently termed persistent fetal vasculature). In 1 case there was total lens replacement with lamellar bone; in another, total replacement of the crystalline lens by adipose tissue; and in a third, an anomalous pocket of adipose tissue in the central vitreous. Multifocal remnants of the lens capsule were seen in the osseous case but were absent from the adipocytic cases. The vitreous adipose tissue was surrounded by an elaborate capillary plexus with an empty, collapsed PAS-positive lens capsule in the pupillary region. Anterior pigmented neuroectodermal disorganization, dysgenesis of angle structures, and a hypoplastic or disorganized iris were also observed in the 3 cases. CONCLUSIONS: After review of the literature, it appears that lenticular osseous replacement occurs more often than adipocytic. In addition to vascularization of the lens through a capsular dehiscence, other causes are explored, including direct epithelial-mesenchymal transformations of the lens epithelium or, less likely, of the disorganized adjacent neuroectoderm. The focus of vitreous adipose tissue may represent a transformed luxated lens extruded from its capsule, which was left behind in the pupillary zone.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.11.014},
	author = {Jakobiec, Frederick A and Ma, Lina and Wolkow, Natalie and Cameron, J Douglas and Maltry, Amanda C}
}
@article {1511479,
	title = {Clinical Implications of Goblet Cells in Dacryoadenosis and Normal Human Lacrimal Glands},
	journal = {Am J Ophthalmol},
	volume = {213},
	year = {2020},
	month = {2020 May},
	pages = {267-282},
	abstract = {PURPOSE: The purpose of this study was to investigate an enlarged dacryoadenotic lacrimal gland and normal lacrimal glands for the presence of goblet cells (mucocytes). DESIGN: Retrospective clinicopathologic series. METHODS: An enlarged lacrimal gland (dacryoadenosis) without obvious histopathologic alterations was extensively evaluated histochemically, immunohistochemically, and ultrastructurally to detect the presence of goblet cells and to compare the findings with those in five normal lacrimal glands. RESULTS: Granular, zymogen-rich pyramidal acinar cells in normal glands predominated over a previously not reported subpopulation of nongranular, pale-staining cells in both dacryoadenotic and normal lacrimal glands. These cells histochemically stained positively with mucicarmine and Alcian blue. Immunohistochemical and electron microscopic evaluations established that there was a displacement or replacement of cytoplasmic gross cystic disease fluid protein-15 and CK 7-positive tonofilaments in the pale acinar cells by myriad mucus granules. The goblet cells constituted approximately 2\% of the normal acinar cells and 5\% of dacryoadenotic acinar cells. A depletion of myoepithelial cells and ectopic intra-acinar ductular cells were also observed in dacryoadenosis. CONCLUSION: Dacryoadenosis is caused by an increase in the number of acini without individual acinar cell hyperplasia. A normal cytologic feature of the lacrimal gland is the presence of acinar goblet cells that had been long overlooked; they are increased in number in dacryoadenosis. Intra-acinar ductular cells and the scattered loss of myoepithelial cells are other abnormalities in dacryoadenosis. The presence of lacrimal gland goblet cells may have physiologic implications for the precorneal tear film and its derangements as well as for the histogenesis of mucus-producing carcinomas.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.01.029},
	author = {Jakobiec, Frederick A and Eagle, Ralph C and Selig, Martin and Ma, Lina and Shields, Carol}
}
@article {1504062,
	title = {Conjunctival Implantation Cyst in the Orbicularis Oculi Muscle: Review of a Possible Origin From Displaced Stem Cells With a Differential Diagnosis},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {37},
	number = {1},
	year = {2021},
	month = {2021 Jan-Feb 01},
	pages = {1-11},
	abstract = {PURPOSE: To document a unique case of a corneal/conjunctival epithelial inclusion cyst located in the orbicularis oculi muscle with a comprehensive review of variant conjunctival cysts and simulating conditions. METHODS: Clinicopathologic case report with detailed histopathologic and immunohistochemical evaluation for cytokeratins combined with a tabulation of mimicking lesions and relevant literature citations. RESULTS: A 59-year-old man experienced severe blunt left periorbital trauma that resulted in a limbal partial-thickness corneal wound with an associated epithelial abrasion and a full-thickness eyelid laceration extending from the superior fornix to the margin. Several months after surgical repair of the eyelid a cyst appeared in the superior pretarsal skin. Histopathologic and immunohistochemical investigations supplied data suggesting that the cyst had a high probability of a corneoscleral limbal stem cell origin. Distinctive features of the lesion are contrasted with those of allied or simulating cysts. CONCLUSIONS: Stem cells are now believed to be located at the corneoscleral limbus, in the inferior fornix, in the medial canthal region, and at the eyelid margin where transitions from conjunctival epithelium to epidermal epithelium occur. Due to their replicative, hardy and robust nature, stem cells displaced to alien environments are most likely to survive and produce cysts. The cyst{\textquoteright}s corneal-type cytologic characteristics, the absence of goblet cells, and the expression of a broad spectrum of cytokeratin biomarkers in the current case give support to the proposal that limbal stem cells in the region of the corneal laceration were displaced to the eyelid orbicularis muscle and were responsible for this most extraordinary cyst. Comparison with other epithelial cystic linings lends further evidence for this conclusion.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001631},
	author = {Jakobiec, Frederick A and Hanbazazh, Mehenaz and Barrantes, Paula Cortes and Yoon, Michael K}
}
@article {417021,
	title = {Lymphoepithelial Carcinoma of the Nasolacrimal Duct: Clinical, Radiologic, and Immunopathologic Features.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 Apr 20},
	abstract = {Undifferentiated lymphoepithelial carcinoma (exhibiting both begin lymphoid and malignant epithelial components) most commonly arises in the head and neck, especially in the nasopharynx. It may also be encountered in various ocular adnexal sites, including the nasolacrimal duct. A 63-year-old woman developed a swelling in the region of the right lacrimal sac accompanied by epiphora. CT scanning revealed an enlargement of the nasolacrimal duct from the lacrimal sac to the inferior nasal meatus. A biopsy during dacryocystorhinostomy for symptomatic epiphora revealed hypercellular sheets of small lymphocytes which were interpreted as evidence for a chronic dacryocystitis. Two years later the subtotally excised lesion had substantially grown in size. Repeat CT scans demonstrated an inferonasal anterior orbital mass with further enlargement of the nasolacrimal duct with a solid mass in its lumen, and bone erosion. The biopsy combined a rich background of lymphocytes within which were clusters of undifferentiated carcinoma cells that were cytokeratin and p63 positive. Critical review of the earlier biopsy led to the detection of the same cells, but in smaller numbers, that had been overlooked. An awareness of the possibility of lymphoepithelial carcinoma of the lacrimal sac/duct should improve diagnostic accuracy with the aid of immunohistochemistry. Radiation therapy is often successful in managing this highly sensitive malignant tumor.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000478},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Rubin, Peter A D}
}
@article {1109821,
	title = {Exophytic Osteochondroma of the Brow},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {6},
	year = {2017},
	month = {2017 Nov/Dec},
	pages = {e166-e169},
	abstract = {Most bony and cartilaginous lesions of the orbit and periorbital compartments are benign, grow endophytically, and are composed of dense lamellar bone (eburnated or ivory osteomas). An 87-year-old woman had a well-circumscribed, firm, round, and exophytic lesion of the brow region for at least 15 years. Excisional surgery disclosed an osteocartilaginous lesion with an enveloping pseudocapsule (periosteum/perichondrium) and a narrow stalk connecting it to the frontal bone. The periphery of the lesion displayed lamellar bone which appeared to be replacing a central cartilaginous zone. The adjacent deep preaponeurotic fat displayed nodules of collagen with myxoid change and occasional CD34 spindle cells suggestive of a spindle cell lipoma. Because of the osteochondroma{\textquoteright}s deep location in the preaponeurotic fat, the lesion differs from an osteoma cutis found in the dermis which fails to exhibit a cartilaginous component or a periosteum. Other clinically simulating lesions are described.},
	keywords = {Aged, 80 and over, Biopsy, Bone Neoplasms, Female, Humans, Orbit, Orbital Neoplasms, Osteochondroma},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000943},
	author = {Jakobiec, Frederick A and Zakka, Fouad R and Lee, Nahyoung Grace}
}
@article {1363127,
	title = {Biopsy of an anterior episcleral nodule as an aid in managing a ciliary body melanocytic tumor},
	journal = {Cornea},
	volume = {32},
	number = {8},
	year = {2013},
	month = {2013 Aug},
	pages = {1174-7},
	abstract = {PURPOSE: To demonstrate the value of a diagnostic biopsy of a fixed episcleral nodule overlying a uveal mass. METHOD: Clinicopathologic report with immunohistochemical investigations. RESULTS: B-scan ultrasonographic biomicroscopy disclosed in a 67-year-old man an asymptomatic placoid ciliary body tumor measuring 1.28 mm in thickness underlying a poorly pigmented, fixed episcleral nodule 0.56 mm in thickness. Biopsy of the episcleral nodule displayed benign nevus-type spindle cells with small nuclei, punctate nucleoli, no mitoses, and scattered melanophages. Immunohistochemistry demonstrated that the tumor cells were Ki67 negative (proliferation index, 0) and MART-1, HMB-45, and microphthalmia-associated transcription factor positive, all melanocytic markers. The melanophages but not the tumor cells were CD68 positive, a histiocytic marker. CONCLUSIONS: The results from biopsying an episcleral nodule can help to select among therapeutic options in managing an associated ciliary body tumor. A 1-year follow-up study and 3 sequential ultrasonographic studies in the current patient have failed to document the growth of the intraocular tumor, further confirming that it is a nevus. The excised epibulbar tumor has not recurred.},
	keywords = {Aged, Biopsy, Ciliary Body, Humans, Male, Melanoma, Uveal Neoplasms},
	issn = {1536-4798},
	doi = {10.1097/ICO.0b013e31829131f8},
	author = {Jakobiec, Frederick A and Gragoudas, Evangelos S and Colby, Kathryn A}
}
@article {1125321,
	title = {Ellipsoid Smooth Muscle Tumor of the Lower Eyelid: An Exploration of Its Possible Origin},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {34},
	number = {1},
	year = {2018},
	month = {2018 Jan/Feb},
	pages = {e6-e10},
	abstract = {Ocular adnexal smooth muscle masses/neoplasms are extremely rare. Such lesions are comparatively more common in the conjunctiva than in the orbit and are most unusual in the eyelid. A 58-year-old woman slowly developed over 4 months a firm, movable sausage-shaped lesion in the deep lateral half of the right lower eyelid. The lesion ran parallel to and above the orbital rim. At surgery, the lesion was located between the orbicularis muscle and the inferior orbital septum. The term ellipsoid is used descriptively and does not imply any particular biologic behavior. Immunohistochemical evaluation revealed smooth muscle actin and desmin positivity. Due to the ubiquity of small blood vessels and the absence of smooth muscle bundles in the potential space between the orbicularis striated muscle and the inferior orbital septum, venular smooth muscle emerges as a highly likely source for the lesion.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000956},
	author = {Jakobiec, Frederick A and Zakka, Fouad R and Bojovic, Branko}
}
@article {1532364,
	title = {Subretinal Mononuclear Cells in Coats{\textquoteright} Disease Studied with RPE65 and CD163: Evidence for Histiocytoid Pigment Epithelial Cells},
	journal = {Am J Ophthalmol},
	year = {2020},
	month = {2020 Sep 17},
	abstract = {PURPOSE: To evaluate the mononuclear cells in the subretinal exudate in Coats{\textquoteright} disease. DESIGN: Retrospective case series. METHODS: Five enucleated globes and one cytology sample with Coats{\textquoteright} disease and one case of chronic retinal detachment following repair of an open globe injury were examined immunohistochemically to identify the intraretinal and subretinal exudative cells. The two biomarkers were RPE65 for retinal pigment epithelium and CD163 for histiocytes, each tagged with different chromogens, yellow for pigment epithelium and purple for CD163+ monocytes/histiocytes. Expressions were sought of both biomarkers together or singly. A color shift to red in the cells{\textquoteright} chromogenic reaction indicated the simultaneous presence of the two biomarkers. RESULTS: The majority of the mononuclear cells in Coats{\textquoteright} disease were CD163 (purple) positive, and a minority were RPE65 (yellow) positive. An intermediate number of cells were RPE65/CD163 positive (orange-red). The eye with a chronic retinal detachment had an equal distribution of CD163 positive and RPE65/CD163 positive cells. CONCLUSIONS: The retinal pigment epithelium has several well-delineated phenotypes and functions. In normal visual physiology, the pigment epithelium supports the photoreceptors and participates in their renewal by phagocytosis of the tips of the photoreceptors. The expression of CD163, a feature of hematopoietically derived monocytes, together with RPE65 in the retinal pigment epithelium, supports differentiation toward histiocytes. Yellow staining detached pigment epithelial cells were rare. The presence of histiocytoid pigment epithelium at the level of Bruch{\textquoteright}s membrane probably also has implications for macular degeneration.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.09.020},
	author = {Jakobiec, Frederick A and Barrantes, Paula Cortes and Yonekawa, Yoshihiro and Lad, Eleonora M and Proia, Alan D}
}
@article {341761,
	title = {Dystrophic hyaloid artery remnants and other abnormalities in a buphthalmic eye with retinoblastoma.},
	journal = {Surv Ophthalmol},
	volume = {59},
	number = {6},
	year = {2014},
	month = {2014 November - },
	pages = {636-642},
	abstract = {Partial persistence of the hyaloid artery unaccompanied by hyperplastic primary vitreous has not been previously reported in association with retinoblastoma. We describe an 18-month-old child with such a finding who had a retinoblastoma that was undifferentiated, extensively necrotic, heavily calcified, and completely filled the eyeball. The enucleated globe harbored a nonperfused, fossilized remnant of the hyaloid artery due to DNA/calcium deposition in the vascular wall. This structure inserted into a lenticular, extracapsular, fibrous plaque corresponding to a Mittendorf dot. The tumor had induced a placoid cataractous lens, obliterated the anterior and posterior chambers, caused glaucoma leading to buphthalmos, and extended into the optic nerve and extraocularly to involve the orbit. We conclude that the retinoblastoma arose early in ocular morphogenesis, at around 4\&nbsp;months gestation, when the programmed involution of the hyaloid artery begins. This process would typically end at 7-8\&nbsp;months gestation, but was aborted by the tumor. The patient died 6\&nbsp;weeks after surgery without receiving further treatment because of the parents{\textquoteright} resistance.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2014.05.002},
	author = {Jakobiec, Frederick A and Rai, Ruju and Rashid, Alia and Kanoff, Justin and Mukai, Shizuo}
}
@article {303956,
	title = {Granulomatous dacryoadenitis in regional enteritis (crohn disease).},
	journal = {Am J Ophthalmol},
	volume = {158},
	number = {4},
	year = {2014},
	month = {2014 Oct},
	pages = {838-844.e1},
	abstract = {PURPOSE: To evaluate the clinical and immunopathologic features of 2 patients with bilateral dacryoadenitis associated with regional enteritis. DESIGN: Retrospective, clinicopathologic study. METHODS: Clinical records, photographs, and imaging studies were reviewed and microscopic sections of lacrimal gland biopsy samples were critically re-evaluated. The microscopic slides were stained with hematoxylin and eosin, special stains for organisms, and a range of immunohistochemical biomarkers, including CD3, CD4, CD5, CD8, CD20, CD68, CD138, CD1a, and immunoglobulins Ig G, IgG4, and IgA. RESULTS: Both patients were young women with a well-established diagnosis of regional enteritis. Histopathologic examination of biopsy samples disclosed moderate intraparenchymal fibrosis and lymphoplasmacytic infiltrates without lymphoid follicles. Small to medium intraparenchymal, noncaseating granulomas lacking multinucleated giant cells and, in 1 patient, CD68-positive and CD1a-negative palisading granulomas in widened interlobular fibrous septa were detected. Vasculitis and IgG4 plasma cells were not observed. Additional immunohistochemical studies revealed that CD8\&nbsp;T lymphocytes (suppressor or cytotoxic subset) predominated over CD4-positive T lymphocytes (helper cells) surrounding the necrobiotic foci and were intermixed with the CD68-positive histiocytes in the absence of CD20 B lymphocytes. Special stains for organisms demonstrated negative results. CONCLUSIONS: Dacryoadenitis is the rarest form of ocular adnexal involvement in regional enteritis, which affects the orbit far more frequently than ulcerative colitis. It is a granulomatous process with the possibility of palisading necrobiotic foci. In contrast, ulcerative colitis causes an interstitial lymphocytic and nongranulomatous myositis. Sarcoidosis, Wegener granulomatosis, and pseudorheumatoid nodules must be ruled out. Treatment options entail a wide variety of agents with selection based on empirical considerations and tailored to the patient{\textquoteright}s symptoms.},
	keywords = {Adult, Anti-Inflammatory Agents, Non-Steroidal, Antigens, CD, Biological Markers, CD8-Positive T-Lymphocytes, Crohn Disease, Dacryocystitis, Female, Granulomatous Disease, Chronic, Humans, Immunoenzyme Techniques, Magnetic Resonance Imaging, Retrospective Studies, Sulfasalazine, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Helper-Inducer},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.07.011},
	author = {Jakobiec, Frederick A and Rashid, Alia and Lane, Katherine A and Kazim, Michael}
}
@article {742256,
	title = {Orbital Inflammation in Pregnant Women.},
	journal = {Am J Ophthalmol},
	volume = {166},
	year = {2016},
	month = {2016 Jun},
	pages = {91-102},
	abstract = {OBJECTIVE: To analyze overlaps between pregnancy and orbital inflammation (OI). DESIGN: Retrospective observational case series. METHODS: Eight new cases from 1997 to 2015 and 2 previously published cases were identified for inclusion in this investigation to provide the fullest clinical picture. Medical records, imaging studies, and the results of biopsies were reviewed. RESULTS: Three categories of association were discovered: (1) OI arising for the first time during pregnancy (5 cases); (2) OI arising within 3\&nbsp;months of delivery (2\&nbsp;cases); and (3) previously diagnosed OI reactivated or exacerbated by pregnancy (3 cases). One patient had a preexistent systemic autoimmune disease and another{\textquoteright}s was later diagnosed. One patient had attacks during sequential pregnancies. Findings included eyelid swelling and erythema, conjunctival chemosis, pain on eye movement, minimal diplopia, the usual absence of proptosis, and general preservation of visual acuity. Imaging studies disclosed extraocular muscle swelling (8 cases), most frequently of a single lateral rectus muscle. There were 2 cases of dacryoadenitis; 1 of these and an additional case displayed inflammation of the retrobulbar fat. Corticosteroids effected resolution of most symptoms. Singleton births were normal with the exceptions of an intrauterine fetal demise owing to acrania and a molar pregnancy. CONCLUSION: OI usually affects a single rectus muscle (typically the lateral) and, less often, the lacrimal gland and is often mild when it arises during or after pregnancy. Independent systemic autoimmune disease is an uncommon feature. Corticosteroids were efficacious except in 1\&nbsp;case with severe orbital scarring. No definitive causal relationships between pregnancy and OI could be established based on the clinical data.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.03.029},
	author = {Jakobiec, Frederick A and Syed, Zeba A and Stagner, Anna M and Harris, Gerald J and Rootman, Jack and Yoon, Michael K and Mombaerts, Ilse}
}
@article {1363124,
	title = {Clinicopathologic and immunohistochemical studies of conjunctival large cell acanthoma, epidermoid dysplasia, and squamous papilloma},
	journal = {Am J Ophthalmol},
	volume = {156},
	number = {4},
	year = {2013},
	month = {2013 Oct},
	pages = {830-46},
	abstract = {PURPOSE: To evaluate clinicopathologically and immunohistochemically a spectrum of conjunctival squamous proliferations. DESIGN: Retrospective clinicopathologic study. METHODS: One large cell acanthoma, 7 epidermoid dysplasias, and 4 squamous papillomas were evaluated with microscopy and biomarkers Ki-67, p53, epithelial membrane antigen (EMA), Ber-EP4, AE1, AE3, and 8 individual cytokeratins. Normal associated conjunctiva served as a baseline for interpretation. RESULTS: The large cell acanthoma recurred 4 times but retained its benign histopathologic features. The cells were 2-3 times larger than the keratinocytes of the normal conjunctiva and did not display atypia. Immunohistochemistry revealed a low Ki-67 proliferation index (PI) in the large cell acanthoma compared with high indices in dysplasias and papillomas. p53 was negative in the nuclei of normal epithelium while positive in all neoplasms, most intensely in the dysplasias. Immunostaining showed similar staining patterns for cytokeratins in large cell acanthoma and normal conjunctiva, except for full-thickness CK14 positivity and CK7 negativity in the lesion. Dysplasias generally lost normal CK7 expression and frequently abnormally expressed CK17. The papillomas displayed a normal cytokeratin pattern but exhibited a higher than normal PI and weak p53 positivity. CONCLUSIONS: Conjunctival large cell acanthoma is a morphologically distinctive clonal entity with clinical and immunohistochemical phenotypic characteristics denoting a dysplasia of minimal severity. Because of recurrences without invasion, it requires treatment. Dysplasias exhibited more deviant biomarker abnormalities including frequent aberrant full-thickness CK17 positivity and CK7 negativity. The absence of major cytokeratin derangements in the squamous papillomas may be\&nbsp;of ancillary diagnostic value for lesions displaying borderline cytologic features.},
	keywords = {Acanthoma, Adult, Aged, Aged, 80 and over, Antigens, Neoplasm, Biomarkers, Tumor, Carcinoma in Situ, Conjunctival Neoplasms, Female, Humans, Immunoenzyme Techniques, Male, Middle Aged, Neoplasm Proteins, Neoplasm Recurrence, Local, Papilloma, Paraffin Embedding, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.05.005},
	author = {Jakobiec, Frederick A and Mendoza, Pia R and Colby, Kathryn A}
}
@article {591211,
	title = {Conjunctival Primary Acquired Melanosis: Is It Time for a New Terminology?},
	journal = {Am J Ophthalmol},
	volume = {162},
	year = {2016},
	month = {2016 Feb},
	pages = {3-19.e1},
	abstract = {PURPOSE: To review the diagnostic categories of a group of conditions referred to as "primary acquired melanosis." DESIGN: Literature review on the subject and proposal of an alternative diagnostic schema with histopathologic and immunohistochemical illustrations. METHODS: Standard hematoxylin-eosin-stained sections and immunohistochemical stains for MART-1, HMB-45, microphthalmia-associated transcription factor (MiTF), and Ki-67 for calculating the proliferation index are illustrated. RESULTS: "Melanosis" is an inadequate and misleading term because it does not distinguish between conjunctival intraepithelial melanin overproduction ("hyperpigmentation") and intraepithelial melanocytic proliferation. It is\&nbsp;recommended that "intraepithelial melanocytic proliferation" be adopted for histopathologic diagnosis. Atypical proliferations are characterized either by bloated dendritic melanocytes with enlarged cell components (dendrites, cell bodies, and nuclei) or by epithelioid melanocytes without dendrites. Atypical polygonal or epithelioid pagetoid cells may reach higher levels of the epithelium beyond the basal layer. Immunohistochemistry defines the degree of melanocytic proliferation or the cellular shape (dendritic or nondendritic) (MART-1, HMB-45) or identifies the melanocytic nuclei (MiTF). Intraepithelial melanocytic proliferation without atypia represents increased numbers of normal-appearing dendritic melanocytes (hyperplasia or early neoplasia) that generally remain confined to the basal/basement membrane region. Intraepithelial nonproliferative melanocytic pigmentation signifies the usually small number of conjunctival basal dendritic melanocytes that synthesize increased amounts of melanin that is transferred to surrounding keratinocytes. CONCLUSION: All pre- and postoperative biopsies of flat conjunctival melanocytic disorders should be evaluated immunohistochemically if there is any question regarding atypicality. This should lead to a clearer microscopic descriptive diagnosis that is predicated on an analysis of the participating cell types and their architectural patterns. This approach is conducive to a better appreciation of features indicating when to intervene therapeutically. An accurate early diagnosis should forestall unnecessary later surgery.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.11.003},
	author = {Jakobiec, Frederick A}
}
@article {987981,
	title = {Eyelid Eccrine Cyst: An Exceptional Lesion Among Dominant Apocrine Cysts},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {5},
	year = {2017},
	month = {2017 Sep/Oct},
	pages = {e128-e131},
	abstract = {A 71-year-old woman developed a small bluish lesion beneath the cilia of the left lower eyelid. Excision and microscopic examination disclosed a cyst with an intimately associated eccrine sweat gland. Immunohistochemistry demonstrated that the cyst{\textquoteright}s epithelium was strongly CK5/6, CK14, CK7 weakly positive, and gross cystic disease fluid protein-15 and smooth muscle actin negative. This is the first immunohistochemically proven eccrine cyst of the eyelid skin. Apocrine cysts develop only at the eyelid margin where the glands of Moll are located. They immunostain positively for cytoplasmic gross cystic disease fluid protein-15 in the adlumenal cells and smooth muscle actin in an outer myoepithelial (abluminal) layer.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000855},
	author = {Jakobiec, Frederick A and Qureshi, Sana and Zakka, Fouad R and Tu, Yufei and Lee, Nhayoung Grace}
}
@article {369101,
	title = {Caruncular dacryops.},
	journal = {Cornea},
	volume = {34},
	number = {1},
	year = {2015},
	month = {2015 Jan},
	pages = {107-9},
	abstract = {PURPOSE: To report a case of caruncular dacryops in a 58-year-old man that was excised in its entirety and to offer an immunohistopathologic analysis. METHODS: Sections stained with hematoxylin and eosin, periodic acid-Schiff, and Grocott methenamine silver (the latter 2 for identification of mucus) were evaluated, and immunohistochemical investigations were performed using cytokeratin (CK) 7, CK14, CK17, and smooth muscle actin. RESULTS: Histopathologic examination revealed a cystic dilation of the lacrimal gland ducts containing secretory globules. The ducts were composed of double-layered cuboidal epithelium with rare scattered goblet cells and interspersed prominent lobules of lacrimal gland tissue, diagnostic of dacryops. Immunohistochemistry of cystic ducts demonstrated a CK profile identical to that of the conjunctiva including the absence of a myoepithelium. CONCLUSIONS: This is the first case of an intact caruncular lacrimal ductal cyst (dacryops). A previous report documented a spontaneously collapsed cyst with extrusion of secretory globoid bodies into extracellular space that elicited a foreign body giant cell response.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000287},
	author = {Jakobiec, Frederick A and Roh, Miin and Stagner, Anna M and Yoon, Michael K}
}
@article {541346,
	title = {Pigmentation of the Lacrimal Sac Epithelium.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 Sep 3},
	abstract = {PURPOSE: To describe the patterns of the melanocytic populations of 3 cases of lacrimal sac benign melanosis and 1 of atypical primary-acquired sac melanosis with a melanomatous nodule secondary to spread of atypical conjunctival primary-acquired melanosis to the sac. METHODS: Clinical records, photographs, and paraffin sections stained with hematoxylin and eosin and the Fontana reaction were critically reviewed. Additional sections were immunoreacted for melanoma antigen recognized by T cells and microphthalmia-associated transcription factor. Five nonpigmented pterygia and 4 nonpigmented lacrimal sacs served as controls. RESULTS: Three patients with obstructive dacryocystitis and benign melanosis were African-Americans whose sacs disclosed the presence of nonclustering, melanoma antigen recognized by T cells, and microphthalmia-associated transcription factor-positive intraepithelial dendritic melanocytes at all levels of the epithelium. The transferred melanin granules were concentrated in the adlumenal apical region of the epithelial cells. No fusiform melanocytes were found in the lamina propria. The fourth patient, a Caucasian, had atypical conjunctival and sac primary-acquired melanosis and conjunctival and sac melanomas. The intraepithelial sac melanocytes in this case were strikingly atypical and profusely distributed in a back to back fashion at all levels of a thickened epithelial layer focally approximating the appearance of a melanoma in situ. Five nonpigmented pterygia and 4 nonpigmented lacrimal sacs served as controls. Each displayed nonnesting dendritic melanocytes of various densities without back to back contact. CONCLUSION: Low densities of intraepithelial melanocytes were discovered in all controls and therefore represent a normal subpopulation within the conjunctival and lacrimal sacs. Due to the pseudostratification of the sac epithelium, melanocytes can move to higher levels without implying atypia. Benign melanosis is produced by small diffusely distributed individual intraepithelial melanocytes, whereas primary-acquired melanosis with atypia exhibits back to back, dense proliferations of large atypical melanocytes.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000541},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Sutula, Francis C and Freitag, Suzanne K and Yoon, Michael K}
}
@article {280701,
	title = {Papillary hidradenoma of the eyelid margin: clinical and immunohistochemical observations further supporting an apocrine rather than an eccrine origin},
	journal = {Surv Ophthalmol},
	volume = {59},
	number = {5},
	year = {2014},
	month = {2014 Sep-Oct},
	pages = {540-7},
	abstract = {A 46-year-old woman was evaluated for a "recurring papilloma" of the left medial upper eyelid margin. Beneath the papillary lesion medial to the punctum was a 5-mm diameter cutaneous mass thought to be cystic. After excisional biopsy, histopathologic analysis documented the presence of an epidermal keratinizing squamous papilloma surmounting a circumscribed dermal papillary hidradenoma composed of deeply eosinophilic columnar cells. Additionally, there was intraductal proliferation of tumor extending toward a subclinical poral opening through the epidermis. Immunohistochemistry proved the apocrine nature of the benign, non-cystic lesion by virtue of its nuclear androgen receptor and cytoplasmic gross-cystic disease fluid protein-15 positivity, along with its smooth muscle actin-positive myoepithelial layer. This and prior cases establish that apocrine tumors, both benign and malignant, are strictly localized at or near the eyelid margin where only apocrine glands are found. These tumors are more often papillary than solid adenomas, and most exceptionally can be malignant. We review the differential diagnosis of simulating eccrine eyelid tumors. We recommend wide local excision for benign lesions, in view of possible intraductal extension that can be eccentric to the main tumor and the miniscule potential for malignant transformation. },
	keywords = {Acrospiroma, Apocrine Glands, Biomarkers, Tumor, Diagnosis, Differential, Eccrine Glands, Eyelid Neoplasms, Female, Humans, Immunohistochemistry, Middle Aged, Neoplasm Proteins, Sweat Gland Neoplasms},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2014.01.002},
	author = {Jakobiec, Frederick A and Rai, Ruju and Lefebvre, Daniel R}
}
@article {382591,
	title = {Choristomatous Respiratory Cyst Restricted to the Upper Eyelid.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {1},
	year = {2016},
	month = {2016 Jan-Feb},
	pages = {e15-8},
	abstract = {A 79-year-old man underwent excision of an upper eyelid mass that had been enlarging for 3 months. Histopathologic evaluation demonstrated a cyst lined by pseudostratified columnar epithelium with myriad goblet cells and cilia, and immunostaining revealed cytokeratins indicative of a respiratory origin. This rare condition, the first described exclusively in an eyelid, arises either from a congenital embryologic respiratory epithelial ectopia or the displacement of mature sinus mucosa following trauma or chronic sinus disease. The current case lacked any signs or symptoms of sinus disease or a history of trauma.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000373},
	author = {Jakobiec, Frederick A and Roh, Miin and Stagner, Anna M and Yoon, Michael K}
}
@article {1417564,
	title = {Myeloid Sarcoma with Megakaryoblastic Differentiation Arising in the Conjunctiva},
	journal = {Ocul Oncol Pathol},
	volume = {5},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {28-35},
	abstract = {An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.},
	issn = {2296-4681},
	doi = {10.1159/000488057},
	author = {Jakobiec, Frederick A and Wolkow, Natalie and Zakka, Fouad R and Rubin, Peter A D}
}
@article {439636,
	title = {A Hyalinized Trichilemmoma of the Eyelid in a Teenager.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {1},
	year = {2016},
	month = {2016 Jan-Feb},
	pages = {e9-e12},
	abstract = {A 16-year-old African American male, the youngest patient to date, presented with a well-circumscribed upper eyelid lesion. On excision, the dermal nodule was contiguous with the epidermis, displayed trichohyalin-like bodies in an expanded outer root sheath, and was composed chiefly of small cellular clusters separated by a prominent network of periodic acid Schiff -positive hyaline bands of basement membrane material. The tumor cells were positive for high molecular weight cytokeratins (CK) 5/6, CK14, and CK34βE12 and were negative for CK7, carcinoembryonic antigen and epithelial membrane antigen. Negative S100, glial fibrillary acidic protein, and smooth muscle actin immunoreactions ruled out a myoepithelial lesion. The Ki-67 proliferation index was \&lt;10\%. The diagnosis was a hyalinized trichilemmoma, contrasting with the more common lobular type. As an isolated lesion, trichilemmoma does not portend Cowden syndrome.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000389},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Sassoon, Jodi and Goldstein, Scott and Mihm, Martin C}
}
@article {382406,
	title = {Intraocular Medulloepitheliomas and Embryonal Tumors with Multilayered Rosettes of the Brain: Comparative Roles of LIN28A and C19MC.},
	journal = {Am J Ophthalmol},
	year = {2015},
	month = {2015 Mar 5},
	abstract = {PURPOSE: To compare immunohistochemical and genetic overlaps and differences between intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain. DESIGN: Retrospective histopathologic, immunohistochemical and genetic analysis of 20 intraocular medulloepitheliomas. METHODS: 1) Review of clinical data and hematoxylin and eosin stained sections with 2) immunohistochemical staining of paraffin sections using a polyclonal antibody against the protein LIN28A, and 3) FISH testing for the amplification of the genetic locus 19q13.42 involving the C19MC cluster of miRNA. Ten retinoblastomas served as controls and to determine the specificity of these biomarkers for intraocular medulloepitheliomas. RESULTS: Nineteen of the 20 intraocular medulloepitheliomas were either diffusely or focally LIN28A positive (weak, moderate or strong). The most intense positivity correlated with aggressive behavior such as intraocular tissue invasion or extraocular extension. None of the cases studied by fluorescence in situ hybridization (FISH) harbored an amplicon for C19MC. The ten retinoblastomas were LIN28A and C19MC negative. CONCLUSION: LIN28A has a putative role in oncogenesis and is found only in embryonic cells and malignancies. Intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain both display LIN28A positivity. Only the latter, however, display amplification of the 19q13.42 locus involving C19MC, implying that other causative factors are at play in intraocular medulloepitheliomas. More aggressive tumor behavior within the eye can be partially predicted by LIN28A staining intensity.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.03.002},
	author = {Jakobiec, Frederick A and Kool, Marcel and Stagner, Anna M and Pfister, Stefan M and Eagle, Ralph C and Proia, Alan D and Korshunov, Andrey}
}
@article {1354352,
	title = {Fibrous histiocytoma of the tarsus: clinical and immunohistochemical observations with a differential diagnosis},
	journal = {Cornea},
	volume = {33},
	number = {5},
	year = {2014},
	month = {2014 May},
	pages = {536-9},
	abstract = {PURPOSE: To describe the diagnostic clinical findings and immunopathology of a fibrous histiocytoma of the upper eyelid tarsus of a 42-year-old man. METHODS: Analysis of clinical features and results of histopathologic and immunohistochemical evaluations using antibodies against the biomarkers smooth muscle actin, S100, CD1a, CD3, CD20, CD31, CD34, CD68, CD163, factor XIIIa, adipophilin, androgen receptor, and Ki-67. RESULTS: The skin moved over a firm lesion that was situated in the tarsus and protruded from the palpebral conjunctiva as a whitish flat-domed noninflamed mass that had caused an irritating corneal epitheliopathy. Histopathologically, there was a storiform or spiral nebular growth pattern, a moderate amount of intercellular collagen, and no nuclear atypia or mitotic activity. The main immunohistochemical findings were CD34 and smooth muscle actin negativity among the tumor cells and a scarcity of CD68/163 histiocytes. Androgen receptors were identified in the tumor cells. CONCLUSIONS: CD34 histiocytoma of the tarsus is a rare, benign, and separate entity from a CD34 solitary fibrous tumor. Conservative tarsectomy is curative.},
	keywords = {Adult, Biomarkers, Tumor, Diagnosis, Differential, Eyelid Neoplasms, Histiocytoma, Benign Fibrous, Humans, Immunohistochemistry, Male, Neoplasm Proteins},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000095},
	author = {Jakobiec, Frederick A and Rai, Ruju and Yoon, Michael K}
}
@article {1016066,
	title = {Dermatofibroma of the Eyelid: Immunohistochemical Diagnosis},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {6},
	year = {2017},
	month = {2017 Nov/Dec},
	pages = {e134-e138},
	abstract = {A 66-year-old man developed a painless 2 mm to 3 mm recurrent nodule at the left upper eyelid margin. Excision disclosed a spindle cell lesion without frank atypia or mitotic activity growing in a twisted fascicular pattern often referred to as storiform. All the surgical margins were involved with tumor. Immunohistochemistry demonstrated that many of the constituent spindle and dendritic tumor cells were CD34, factor XIIIa, and CD 163, the latter 2 being biomarkers for monocytic lineage. The lesion was diagnosed as a dermatofibroma rather than a fibrous histiocytoma, a term that should be reserved for more aggressive lesions of deeper fascial planes. Facial dermatofibromas are rarer and more likely than those of the extremities to recur and therefore deserve wider local excision at first surgery with careful and frequent clinical follow ups. Eyelid dermatofibroma has probably often been misdiagnosed as another tumor in the past. Immunohistochemistry can supply valuable biomarker criteria for diagnosis.},
	keywords = {Aged, Antigens, CD, Antigens, CD34, Antigens, Differentiation, Myelomonocytic, Biomarkers, Tumor, Diagnosis, Differential, Eyelid Neoplasms, Eyelids, Factor XIIIa, Histiocytoma, Benign Fibrous, Humans, Immunohistochemistry, Male, Receptors, Cell Surface},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000867},
	author = {Jakobiec, Frederick A and Zakka, Fouad R and Tu, Yufei and Freitag, Suzanne K}
}
@article {1363125,
	title = {Complex orbital angiomyoma with features of a lymphangiohemangioma},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {2},
	year = {2013},
	month = {2013 Mar-Apr},
	pages = {e61-5},
	abstract = {A 31-year-old woman developed left frontal headache and retrobulbar pain with exotropia and mild limitation of upgaze without proptosis. Imaging studies disclosed a circumscribed mass measuring 1.5 cm in the greatest diameter. At surgery, the lesion was adherent to the surrounding normal orbital tissues, making for a difficult and dangerous resection. Histopathologically and immunohistochemically, the lesion was a mixed cavernous angiomatous (CD31-positive) and lymphangiomatous (D2-40-positive) tumor with abundant interstitial smooth muscle. Such lesions can present significant surgical challenges due to incomplete pseudoencapsulation.},
	keywords = {Adult, Female, Hemangioma, Cavernous, Humans, Lymphangioma, Magnetic Resonance Imaging, Neoplasms, Complex and Mixed, Orbital Neoplasms, Tomography, X-Ray Computed, Visual Acuity},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31826b777d},
	author = {Jakobiec, Frederick A and Zakka, Fouad R and Yoon, Michael K}
}
@article {836881,
	title = {Clear-Cell (Reticulated) Transformation of Eyelid Eccrine Sweat Glands.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2016},
	month = {2016 Jul 21},
	abstract = {A 24-year-old man with a painful, recurrent left upper eyelid nodule underwent an excision. Histopathologic evaluation disclosed a granulomatous process, most likely in response to a ruptured epidermoid cyst. In the vicinity of the nodule were multiple eccrine sweat glands displaying a curious clear-cell appearance in the adlumenal cells, the first example of such a phenomenon in the eyelids. Alcian blue, periodic acid Schiff, and documented staining failed to disclose, respectively, any cytoplasmic mucosubstances, glycogen accumulation, or lipid in the adlumenal secretory cells. Cytokeratin 7 immunostained the adlumenal cells of the eccrine secretory coil, while cytokeratin 5/6 stained the ablumenal myoepithelial and ductular cells. Gross cystic disease fluid protein 15, normally demonstrable in the eccrine secretory cells, was not detectable. Clear-cell transformation should not be confused with syringoma of the lower eyelids, in which glycogen is responsible for the ablumenal clear-cell change.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000761},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Lee, Nahyoung Grace}
}
@article {397806,
	title = {Pigmented Caruncular Apocrine Hidrocystoma With Oncocytic Features.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 Mar 18},
	abstract = {An unprecedented pigmented caruncular apocrine hidrocystoma with the additional feature of an oncocytic transformation of the cyst{\textquoteright}s lining cells is reported. Over a year, a 79-year-old woman developed a centrally pigmented lesion of her right caruncle with translucent borders. Because of concern about a melanoma, a carunculectomy with adjunctive cryotherapy and placement of an amniotic membrane graft were performed, and the excised specimen was evaluated microscopically. A large cyst dominated the caruncle and was lined by an inner layer of columnar eosinophilic and granular cells with an outer, interrupted layer of flattened myoepithelial cells. Phosphotungstic acid hematoxylin staining disclosed myriad cytoplasmic, dot-like mitochondria signifying an oncocytic change. Immunohistochemistry revealed gross cystic fluid disease protein-15 and cytokeratin 7-positivity indicative of apocrine differentiation. Oncocytic change is characteristically encountered in lacrimal ductal cysts and tumors.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000441},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Colby, Kathryn A}
}
@article {1522727,
	title = {Adult Primary Capillary Hemangioma of the Sclera: A Previously Undescribed Entity With a Review of Epibulbar Vascular Lesions},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {36},
	number = {4},
	year = {2020},
	month = {2020 Jul/Aug},
	pages = {327-333},
	abstract = {PURPOSE: The objective of this article is to document a unique case of a primary hemangioma and review epibulbar vascular tumors of the conjunctiva and episclera. METHODS: A case report with detailed histopathologic, histochemical, and immunohistochemical studies coupled with a comprehensive review of the relevant literature with a tabulation of previously reported epibulbar vascular lesions was performed. RESULTS: A vascular tumor developed in a 46-year-old woman over 2-3 months that histopathologically was located in the superficial third of the normally avascular sclera and was composed of capillary caliber vessels. CD31 and CD34 positivity established the vascular nature of the lesion. Despite its adult onset, the tumor was also glut-1 positive, a vascular characteristic of childhood capillary hemangiomas that will ultimately involute. Smooth muscle actin was positive in the endothelial cells and associated pericytes. An ectatic muscular vessel identified in the midst of the lesion was interpreted as an anomalous intrascleral branch of an epibulbar anterior ciliary artery, where it perforated the sclera in the vicinity of the insertion of an extraocular rectus muscle. It was deduced to be the source of the capillary proliferation. A literature review failed to identify any previously reported epibulbar vascular tumor that originated primarily in the sclera or secondarily infiltrated this ocular tunic. CONCLUSION: An adult primary capillary intrascleral neoplasm is described as the rarest of all epibulbar vascular tumors and in keeping with the exceptional status of the ocular endothelium was glut-1 positive. This lesion must be distinguished from an array of other common and esoteric epibulbar vascular conditions.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001582},
	author = {Jakobiec, Frederick A and Hanbazazh, Mehenaz and Barrantes, Paula Cortes and Chodosh, James}
}
@article {591201,
	title = {Uniformly Sclerotic Diffuse Large B-Cell Lymphoma of the Orbit.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 Nov 11},
	abstract = {Over a year, a 51-year-old man developed a mass in the anteromedial orbit in the region of the lacrimal sac that caused epiphora. Imaging studies disclosed no bone destruction. On biopsy, a sclerotic lesion was discovered populated by hyperchromatic cells that had been apparently distorted by crush artifact, indicative of fragile cells. The lesion simulated a sclerosing inflammatory process or a desmoplastic metastatic carcinoma. CD20 revealed that the background cells were large neoplastic B-lymphocytes. A systemic workup uncovered widespread skeletal disease. The patient is undergoing R-CHOP chemotherapy with a relatively favorable prognosis due to negative testing for MYC.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000588},
	author = {Jakobiec, Frederick A and Stagner, Anna M and Lefebvre, Daniel R}
}
@article {1016071,
	title = {Ex Vivo Imaging of the Murine Optic Nerve Head},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {2},
	year = {2017},
	month = {2017 Feb 01},
	pages = {734},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-21422},
	author = {Jakobs, Tatjana C}
}
@article {313186,
	title = {Differential gene expression in glaucoma.},
	journal = {Cold Spring Harb Perspect Med},
	volume = {4},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {a020636},
	abstract = {In glaucoma, regardless of its etiology, retinal ganglion cells degenerate and eventually die. Although age and elevated intraocular pressure (IOP) are the main risk factors, there are still many mysteries in the pathogenesis of glaucoma. The advent of genome-wide microarray expression screening together with the availability of animal models of the disease has allowed analysis of differential gene expression in all parts of the eye in glaucoma. This review will outline the findings of recent genome-wide expression studies and discuss their commonalities and differences. A common finding was the differential regulation of genes involved in inflammation and immunity, including the complement system and the cytokines transforming growth factor β (TGFβ) and tumor necrosis factor α (TNFα). Other genes of interest have roles in the extracellular matrix, cell-matrix interactions and adhesion, the cell cycle, and the endothelin system.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a020636},
	author = {Jakobs, Tatjana C}
}
@article {1490444,
	title = {Resident plasmacytoid dendritic cells patrol vessels in the na{\"\i}ve limbus and conjunctiva},
	journal = {Ocul Surf},
	volume = {18},
	number = {2},
	year = {2020},
	month = {2020 Apr},
	pages = {277-285},
	abstract = {Plasmacytoid dendritic cells (pDCs) constitute a unique population of bone marrow-derived cells that play a pivotal role in linking innate and adaptive immune responses. While peripheral tissues are typically devoid of pDCs during steady state, few tissues do host resident pDCs. In the current study, we aim to assess presence and distribution of pDCs in na{\"\i}ve murine limbus and bulbar conjunctiva. Immunofluorescence staining followed by confocal microscopy revealed that the na{\"\i}ve bulbar conjunctiva of wild-type mice hosts CD45 CD11c PDCA-1 pDCs. Flow cytometry confirmed the presence of resident pDCs in the bulbar conjunctiva through multiple additional markers, and showed that they express maturation markers, the T cell co-inhibitory molecules PD-L1 and B7-H3, and minor to negligible levels of T cell co-stimulatory molecules CD40, CD86, and ICAM-1. Epi-fluorescent microscopy of DPE-GFP{\texttimes}RAG1 transgenic mice with GFP-tagged pDCs indicated lower density of pDCs in the bulbar conjunctiva compared to the limbus. Further, intravital multiphoton microscopy revealed that resident pDCs accompany the limbal vessels and patrol the intravascular space. In vitro multiphoton microscopy showed that pDCs are attracted to human umbilical vein endothelial cells and interact with them during tube formation. In conclusion, our study shows that the limbus and bulbar conjunctiva are endowed with resident pDCs during steady state, which express maturation and classic T cell co-inhibitory molecules, engulf limbal vessels, and patrol intravascular spaces.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.02.005},
	author = {Jamali, Arsia and Harris, Deshea L and Blanco, Tomas and Lopez, Maria J and Hamrah, Pedram}
}
@article {1532330,
	title = {Characterization of Resident Corneal Plasmacytoid Dendritic Cells and Their Pivotal Role in Herpes Simplex Keratitis},
	journal = {Cell Rep},
	volume = {32},
	number = {9},
	year = {2020},
	month = {2020 Sep 01},
	pages = {108099},
	abstract = {The presence and potential functions of resident plasmacytoid dendritic cells (pDCs) in peripheral tissues is unclear. We report that pDCs constitutively populate na{\"\i}ve corneas and are increased during sterile injuries or acute herpes simplex virus 1 (HSV-1) keratitis. Their local depletion leads to severe clinical disease, nerve loss, viral dissemination to the trigeminal ganglion and draining lymph nodes, and mortality, while their local adoptive transfer limits disease. pDCs are the main source of HSV-1-induced IFN-α in the corneal stroma through TLR9, and they prevent re-programming of regulatory T\&nbsp;cells (Tregs) to effector ex-Tregs. Clinical signs of infection are observed in pDC-depleted corneas, but not in pDC-sufficient corneas, following low-dose HSV-1 inoculation, suggesting their critical role in corneal antiviral immunity. Our findings demonstrate a vital role for corneal pDCs in the control of local viral infections.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2020.108099},
	author = {Jamali, Arsia and Hu, Kai and Sendra, Victor G and Blanco, Tomas and Lopez, Maria J and Ortiz, Gustavo and Qazi, Yureeda and Zheng, Lixin and Turhan, Aslihan and Harris, Deshea L and Hamrah, Pedram}
}
@article {1580464,
	title = {Angle Surgery in Pediatric Glaucoma Following Cataract Surgery},
	journal = {Vision (Basel)},
	volume = {5},
	number = {1},
	year = {2021},
	month = {2021 Feb 05},
	abstract = {Glaucoma is a common and sight-threatening complication of pediatric cataract surgery Reported incidence varies due to variability in study designs and length of follow-up. Consistent and replicable risk factors for developing glaucoma following cataract surgery (GFCS) are early age at the time of surgery, microcornea, and additional surgical interventions. The exact mechanism for GFCS has yet to be completely elucidated. While medical therapy is the first line for treatment of GFCS, many eyes require surgical intervention, with various surgical modalities each posing a unique host of risks and benefits. Angle surgical techniques include goniotomy and trabeculotomy, with trabeculotomy demonstrating increased success over goniotomy as an initial procedure in pediatric eyes with GFCS given the success demonstrated throughout the literature in reducing IOP and number of IOP-lowering medications required post-operatively. The advent of microcatheter facilitated circumferential trabeculotomies lead to increased success compared to traditional \&lt;180{\textdegree} rigid probe trabeculotomy in GFCS. The advent of two-site rigid-probe trabeculotomy indicated that similar results could be attained without the use of the more expensive microcatheter system. Further studies of larger scale, with increased follow-up, and utilizing randomization would be beneficial in determining optimum surgical management of pediatric GFCS.},
	issn = {2411-5150},
	doi = {10.3390/vision5010009},
	author = {Jamerson, Emery C and Solyman, Omar and Yacoub, Magdi S and Abushanab, Mokhtar Mohamed Ibrahim and Elhusseiny, Abdelrahman M}
}
@article {1304382,
	title = {Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema},
	journal = {Ophthalmology},
	volume = {125},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {1054-1063},
	abstract = {PURPOSE: To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm. PARTICIPANTS: Participants with available plasma samples (N\&nbsp;= 436). METHODS: Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were\&nbsp;-0.30{\textpm}0.61 pg/ml,\&nbsp;-0.31{\textpm}0.54 pg/ml, and\&nbsp;-0.02{\textpm}0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were\&nbsp;-0.01 (-0.12 to\&nbsp;+0.10; P\&nbsp;= 0.89),\&nbsp;-0.31 (-0.44 to\&nbsp;-0.18; P \&lt; 0.001), and\&nbsp;-0.30 (-0.43 to\&nbsp;-0.18; P \&lt; 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (-0.23 [-0.38 to\&nbsp;-0.09]; P \&lt; 0.001); the difference between aflibercept and ranibizumab was\&nbsp;-0.12 (P\&nbsp;= 0.07) and between aflibercept and bevacizumab was\&nbsp;+0.11 (P\&nbsp;= 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N\&nbsp;= 9) and without (N\&nbsp;= 251) a heart attack or stroke had VEGF levels that appeared similar. CONCLUSIONS: These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay{\textquoteright}s ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.01.019},
	author = {Jampol, Lee M and Glassman, Adam R and Liu, Danni and Aiello, Lloyd Paul and Bressler, Neil M and Duh, Elia J and Quaggin, Susan and Wells, John A and Wykoff, Charles C and Diabetic Retinopathy Clinical Research Network}
}
@article {1504059,
	title = {Evaluation and Care of Patients with Diabetic Retinopathy},
	journal = {N Engl J Med},
	volume = {382},
	number = {17},
	year = {2020},
	month = {2020 04 23},
	pages = {1629-1637},
	keywords = {Angiogenesis Inhibitors, Diabetic Retinopathy, Humans, Intravitreal Injections, Laser Coagulation, Macular Edema, Retina, Vascular Endothelial Growth Factors},
	issn = {1533-4406},
	doi = {10.1056/NEJMra1909637},
	author = {Jampol, Lee M and Glassman, Adam R and Sun, Jennifer}
}
@article {1328889,
	title = {Contribution of noncoding pathogenic variants to RPGRIP1-mediated inherited retinal degeneration},
	journal = {Genet Med},
	volume = {21},
	number = {3},
	year = {2019},
	month = {2019 03},
	pages = {694-704},
	abstract = {PURPOSE: With the advent of gene therapies for inherited retinal degenerations (IRDs), genetic diagnostics will have an increasing role in clinical decision-making. Yet the genetic cause of disease cannot be identified using exon-based sequencing for a significant portion of patients. We hypothesized that noncoding pathogenic variants contribute significantly to the genetic causality of IRDs and evaluated patients with single coding pathogenic variants in RPGRIP1 to test this hypothesis. METHODS: IRD families underwent targeted panel sequencing. Unsolved cases were explored by exome and genome sequencing looking for additional pathogenic variants. Candidate pathogenic variants were then validated by Sanger sequencing, quantitative polymerase chain reaction, and in vitro splicing assays in two cell lines analyzed through amplicon sequencing. RESULTS: Among 1722 families, 3 had biallelic loss-of-function pathogenic variants in RPGRIP1 while 7 had a single disruptive coding pathogenic variants. Exome and genome sequencing revealed potential noncoding pathogenic variants in these 7 families. In 6, the noncoding pathogenic variants were shown to lead to loss of function in vitro. CONCLUSION: Noncoding pathogenic variants were identified in 6 of 7 families with single coding pathogenic variants in RPGRIP1. The results suggest that noncoding pathogenic variants contribute significantly to the genetic causality of IRDs and RPGRIP1-mediated IRDs are more common than previously thought.},
	issn = {1530-0366},
	doi = {10.1038/s41436-018-0104-7},
	author = {Jamshidi, Farzad and Place, Emily M and Mehrotra, Sudeep and Navarro-Gomez, Daniel and Maher, Mathew and Branham, Kari E and Valkanas, Elise and Cherry, Timothy J and Lek, Monkol and MacArthur, Daniel and Pierce, Eric A and Bujakowska, Kinga M}
}
@article {1059766,
	title = {Biallelic mutations in human DCC cause developmental split-brain syndrome},
	journal = {Nat Genet},
	volume = {49},
	number = {4},
	year = {2017},
	month = {2017 Apr},
	pages = {606-612},
	abstract = {Motor, sensory, and integrative activities of the brain are coordinated by a series of midline-bridging neuronal commissures whose development is tightly regulated. Here we report a new human syndrome in which these commissures are widely disrupted, thus causing clinical manifestations of horizontal gaze palsy, scoliosis, and intellectual disability. Affected individuals were found to possess biallelic loss-of-function mutations in the gene encoding the axon-guidance receptor {\textquoteright}deleted in colorectal carcinoma{\textquoteright} (DCC), which has been implicated in congenital mirror movements when it is mutated in the heterozygous state but whose biallelic loss-of-function human phenotype has not been reported. Structural MRI and diffusion tractography demonstrated broad disorganization of white-matter tracts throughout the human central nervous system (CNS), including loss of all commissural tracts at multiple levels of the neuraxis. Combined with data from animal models, these findings show that DCC is a master regulator of midline crossing and development of white-matter projections throughout the human CNS.},
	issn = {1546-1718},
	doi = {10.1038/ng.3804},
	author = {Jamuar, Saumya S and Schmitz-Abe, Klaus and D{\textquoteright}Gama, Alissa M and Drottar, Marie and Chan, Wai-Man and Peeva, Maya and Servattalab, Sarah and Lam, Anh-Thu N and Delgado, Mauricio R and Clegg, Nancy J and Zayed, Zayed Al and Dogar, Mohammad Asif and Alorainy, Ibrahim A and Jamea, Abdullah Abu and Abu-Amero, Khaled and Griebel, May and Ward, Wendy and Lein, Ed S and Markianos, Kyriacos and Barkovich, A James and Robson, Caroline D and Grant, P Ellen and Bosley, Thomas M and Engle, Elizabeth C and Walsh, Christopher A and Yu, Timothy W}
}
@article {1709781,
	title = {Patterns and determinants of incident cataract surgery in China from 2011 to 2015 using a nationally representative longitudinal database},
	journal = {BMJ Open},
	volume = {13},
	number = {6},
	year = {2023},
	month = {2023 Jun 21},
	pages = {e069702},
	abstract = {OBJECTIVES: To investigate incident cataract surgery and to investigate determinants of cataract surgery uptake in Chinese adults. DESIGN: This nationally representative longitudinal study recorded self-reported incident cataract surgery, and measured biological, clinical and socioeconomical characteristics at baseline and endline. SETTING: In the first stage, 150 county-level units were randomly chosen with a probability-proportional-to-size sampling technique from a sampling frame containing all county-level units. The sample was stratified by region and within region by urban district or rural county and per capita gross domestic product. The final sample of 150 counties fell within 28 provinces of China. PARTICIPANTS: Urban and rural Chinese persons aged 45 years and older. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident cataract surgery (primary outcome) and the factors associated with incident cataract surgery (secondary outcome). RESULTS: Among 16 663 people enrolled in 2011, 13 705 (82.2\%) attended follow-up in 2015. Among these, 167 (1.22\%) reported incident cataract surgery. Those receiving surgery were significantly older (66.2{\textpm}8.79 vs 58.3{\textpm}9.18, p<=0.001) and more likely to report: illiteracy (44.9\% vs 27.1\%, p\&lt;0.001), poor baseline distance vision (49.7\% vs 20.0\%, p<=0.001), poor baseline near vision (37.1\% vs 21.8\%, p<=0.001), baseline visual impairment (15.6\% vs 5.5\%, p<=0.001), diabetes (12.0\% vs 7.42\%, p<=0.05) and higher baseline depression scores (9.7 vs 8.4 on a scale of 0-30, p<=0.05). In linear regression models, older age, worse distance vision, hypertension or diabetes, illiteracy and lower depression score were significantly associated with undergoing surgery. Results were similar in models including only persons aged >=60 years, except that urban residence was also associated with surgery. When only those aged >=60 years with poor vision were included, results were again the same, except that higher household expenditure was also associated with surgery. CONCLUSIONS: In China, cataract surgical rates remain low; underserved groups such as rural dwellers are less likely to receive cataract surgery.},
	keywords = {Cataract, Cataract Extraction, China, Humans, Longitudinal Studies, Vision, Low, Visual Acuity},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2022-069702},
	author = {Jan, Catherine and Xin, Jin and Dong, Yanhui and Butt, Thomas and Chang, Robert and Keay, Lisa and He, Mingguang and Friedman, David and Congdon, Nathan}
}
@article {1789241,
	title = {Inability to move one{\textquoteright}s face dampens facial expression perception},
	journal = {Cortex},
	volume = {169},
	year = {2023},
	month = {2023 Dec},
	pages = {35-49},
	abstract = {Humans rely heavily on facial expressions for social communication to convey their thoughts and emotions and to understand them in others. One prominent but controversial view is that humans learn to recognize the significance of facial expressions by mimicking the expressions of others. This view predicts that an inability to make facial expressions (e.g., facial paralysis) would result in reduced perceptual sensitivity to others{\textquoteright} facial expressions. To test this hypothesis, we developed a diverse battery of sensitive emotion recognition tasks to characterize expression perception in individuals with Moebius Syndrome (MBS), a congenital neurological disorder that causes facial palsy. Using computer-based detection tasks we systematically assessed expression perception thresholds for static and dynamic face and body expressions. We found that while MBS individuals were able to perform challenging perceptual control tasks and body expression tasks, they were less efficient at extracting emotion from facial expressions, compared to matched controls. Exploratory analyses of fMRI data from a small group of MBS participants suggested potentially reduced engagement of the amygdala in MBS participants during expression processing relative to matched controls. Collectively, these results suggest a role for facial mimicry and consequent facial feedback and motor experience in the perception of others{\textquoteright} facial expressions.},
	keywords = {Emotions, Facial Expression, Facial Paralysis, Facial Recognition, Humans, Mobius Syndrome, Perception, Social Perception},
	issn = {1973-8102},
	doi = {10.1016/j.cortex.2023.08.014},
	author = {Japee, Shruti and Jordan, Jessica and Licht, Judith and Lokey, Savannah and Chen, Gang and Snow, Joseph and Jabs, Ethylin Wang and Webb, Bryn D and Engle, Elizabeth C and Manoli, Irini and Baker, Chris and Ungerleider, Leslie G}
}
@article {1761876,
	title = {Glaucoma: now and beyond},
	journal = {Lancet},
	volume = {402},
	number = {10414},
	year = {2023},
	month = {2023 Nov 11},
	pages = {1788-1801},
	abstract = {The glaucomas are a group of conditions leading to irreversible sight loss and characterised by progressive loss of retinal ganglion cells. Although not always elevated, intraocular pressure is the only modifiable risk factor demonstrated by large clinical trials. It remains the leading cause of irreversible blindness, but timely treatment to lower intraocular pressure is effective at slowing the rate of vision loss from glaucoma. Methods for lowering intraocular pressure include laser treatments, topical medications, and surgery. Although modern surgical innovations aim to be less invasive, many have been introduced with little supporting evidence from randomised controlled trials. Many cases remain undiagnosed until the advanced stages of disease due to the limitations of screening and poor access to opportunistic case finding. Future research aims to generate evidence for intraocular pressure-independent neuroprotective treatments, personalised treatment through genetic risk profiling, and exploration of potential advanced cellular and gene therapies.},
	keywords = {Blindness, Glaucoma, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Vision Disorders},
	issn = {1474-547X},
	doi = {10.1016/S0140-6736(23)01289-8},
	author = {Jayaram, Hari and Kolko, Miriam and Friedman, David S and Gazzard, Gus}
}
@article {836886,
	title = {Sleep and diabetic retinopathy},
	journal = {Acta Ophthalmol},
	volume = {95},
	number = {1},
	year = {2017},
	month = {2017 Feb},
	pages = {41-47},
	abstract = {PURPOSE: To investigate the association between sleep duration and diabetic retinopathy (DR). METHODS: A population-based cross-sectional study using a nation-wide, systemically stratified, multistage, clustered sampling method included a total of 1670 subjects aged >=40\&nbsp;years with diabetes who participated in the Korean National Health and Nutrition Examination Survey during 2008-2012. All participants performed standardized interviews, including self-reported sleep duration, and comprehensive ophthalmic examinations. Seven standard retinal fundus photographs were obtained from both eyes after pupil dilatation. Diabetic retinopathy (DR) was graded and classified as any DR and vision-threatening DR. Participants were stratified into men and women. RESULTS: The mean sleep duration was 6.71\&nbsp;hr/day. In men, adjusted OR of any DR was 1.88 [95\% confidence interval (OR), 1.01-3.59] in those with <=5\&nbsp;hr sleep, and 2.19 (95\% CI, 1.01-4.89) in those with >=9\&nbsp;hr sleep, compared to in subjects with 6-8\&nbsp;hr sleep, after adjusting for potential confounders including age, body mass index (BMI), diabetes duration, fasting glucose level, haemoglobin A1c levels and hypertension. In women, however, no significant association between sleep duration and DR was found. The vision-threatening DR was not significantly associated with sleep duration in either men or women. CONCLUSIONS: Short and long sleep was associated with high prevalence of DR in men. Sleep deprivation may be involved in the pathogenesis of DR development.},
	keywords = {Adult, Blood Glucose, Body Mass Index, Cluster Analysis, Cross-Sectional Studies, Diabetic Retinopathy, Female, Hemoglobin A, Glycosylated, Humans, Hypertension, Male, Middle Aged, Nutrition Surveys, Prevalence, Republic of Korea, Risk Factors, Sleep, Sleep Deprivation},
	issn = {1755-3768},
	doi = {10.1111/aos.13169},
	author = {Jee, Donghyun and Keum, Nana and Kang, Seungbum and Arroyo, Jorge G}
}
@article {655096,
	title = {Serum 25-Hydroxyvitamin D Levels and Dry Eye Syndrome: Differential Effects of Vitamin D on Ocular Diseases.},
	journal = {PLoS One},
	volume = {11},
	number = {2},
	year = {2016},
	month = {2016},
	pages = {e0149294},
	abstract = {PURPOSE: To investigate associations between serum 25-hydroxyvitamin D levels and dry eye syndrome (DES), and to evaluate the differential effect of vitamin D on ocular diseases including age-related macular disease (AMD), diabetic retinopathy (DR), cataract, and DES. METHODS: A total of 16,396 participants aged \&gt;19 years were randomly selected from the Korean National Health and Nutrition Examination Survey. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. DES was defined by a history of clinical diagnosis of dry eyes by a physician. The association between vitamin D and DES was compared to the associations between vitamin D and AMD, DR, cataract, and DES from our previous studies. RESULTS: The odds of DES non-significantly decreased as the quintiles of serum 25-hydroxyvitamin D levels increased (quintile 5 versus 1, OR = 0.85, 95\%CI: 0.55-1.30, P for trend = 0.076) after adjusting for potential confounders including age, sex, hypertension, diabetes, smoking status, and sunlight exposure times. The relative odds of DES (OR = 0.70, 95\% CI: 0.30-1.64) and cataract (OR = 0.76, 95\% CI: 0.59-0.99) were relatively high, while those of DR (OR = 0.37, 95\% CI: 0.18-0.76) and late AMD (OR = 0.32, 95\% CI: 0.12-0.81) were lower in men. CONCLUSIONS: The present study does not support an association between serum 25-hydroxyvitamin D levels and DES. The preventive effect of serum 25-hydroxyvitamin D may be more effective for DR and late AMD than it is for cataract and DES.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0149294},
	author = {Jee, Donghyun and Kang, Seungbum and Yuan, Changzheng and Cho, Eunyoung and Arroyo, Jorge G and Epidemiologic Survey Committee of the Korean Ophthalmologic Society}
}
@article {742261,
	title = {Positive Association between Blood 25-Hydroxyvitamin D Levels and Pterygium after Control for Sunlight Exposure.},
	journal = {PLoS One},
	volume = {11},
	number = {6},
	year = {2016},
	month = {2016},
	pages = {e0157501},
	abstract = {PURPOSE: To investigate the association between blood 25-hydroxyvitamin D levels and pterygium. METHODS: Korean National Health and Nutrition Examination Survey 2008-2011 were used for the present epidemiologic study. A total of 19,178 participants aged >= 30 years were evaluated for blood 25-hydroxyvitamin D levels and performed ophthalmic slit lamp examinations. Pterygium was considered as a growth of fibrovascular tissue over the cornea. RESULTS: The average blood 25-hydroxyvitamin D levels were 18.6 ng/mL, and prevalence of pterygium was 6.5\%. The odds of pterygium significantly increased across blood 25-hydroxyvitamin D quintiles after controlling sun exposure time as well as other confounders such as sex, age, smoking, diabetes, hypertension (P \&lt; 0.001). The odds ratios (OR) for pterygium was 1.51 (95\% Confidence Interval[95\%CI]; 1.19-1.92) in the highest blood vitamin D quintile. Stratified analysis by sex showed a positive association between blood 25-hydroxyvitamin D levels and pterygium in both men (quintile 5 versus 1, OR; 1.68, 95\%CI; 1.19-2.37) and women (quintile 5 versus 1, OR; 1.37, 95\% CI; 1.00-1.88). CONCLUSIONS: Even after controlling sun light exposure time, we found a positive association between blood 25-hydroxyvitamin D levels and pterygium in a representative Korean population. The mechanism underlying this association is unknown.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0157501},
	author = {Jee, Donghyun and Kim, Eun Chul and Cho, Eunyoung and Arroyo, Jorge G}
}
@article {1598073,
	title = {Fundus Pigmentary Whorls in a Patient With Mosaicism for Tetrasomy 3q},
	journal = {JAMA Ophthalmol},
	year = {2021},
	month = {2021 Jun 17},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.1954},
	author = {Jeng-Miller, Karen W and Alkharashi, Maan and Fulton, Anne and Yonekawa, Yoshihiro}
}
@article {1154946,
	title = {Congenital anomalies of the optic disc: insights from optical coherence tomography imaging},
	journal = {Curr Opin Ophthalmol},
	volume = {28},
	number = {6},
	year = {2017},
	month = {2017 Nov},
	pages = {579-586},
	abstract = {PURPOSE OF REVIEW: Congenital anomalies of the optic nerve are rare but significant causes of visual dysfunction in children and adults. Accurate diagnosis is dependent on a thorough funduscopic examination, but can be enhanced by imaging information garnered from optical coherence tomography (OCT). We review common congenital optic nerve anomalies, including optic disc pit, optic nerve coloboma, morning glory disc anomaly, and hypoplasia of the optic nerve, review their systemic associations, and discuss insights from OCT imaging. RECENT FINDINGS: Optic disc pits are a result of a defect in the lamina cribrosa and abnormal vitreomacular adhesions have been shown to cause maculopathy. In patients with optic nerve colobomas, OCT can be instrumental in diagnosing choroidal neovascularization, a rare but visually devastating complication. The pathogenesis of morning glory disc anomaly has been more clearly elucidated by OCT as occurring from a secondary postnatal mesenchymal abnormality rather than only the initial neuroectodermal dysgenesis of the terminal optic stalk in isolation. OCT studies of optic nerve hypoplasia have demonstrated significant thinning of the inner and outer retinal layers of the perifoveal region and thicker layers in the fovea itself, resulting in a foveal hypoplasia-like pathology, that is, significantly correlated to poorer visual outcomes. SUMMARY: OCT provides detailed in-vivo analysis of these anatomic anomalies and their resulting pathologies, shedding new insights on the pathogenesis, diagnosis, and potential visual outcomes of these conditions in children. Further study employing OCT to elucidate structure-function relationships of congenital optic nerve anomalies will help expand the role of OCT in clinical practice related to diagnosis, prognosis, and management of these entities.},
	keywords = {Coloboma, Humans, Optic Disk, Optic Nerve, Tomography, Optical Coherence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000425},
	author = {Jeng-Miller, Karen W and Cestari, Dean M and Gaier, Eric D}
}
@article {1504069,
	title = {Not the 2020 we asked for},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {741},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316403},
	author = {Jhanji, Vishal and Chodosh, James}
}
@article {1586176,
	title = {Neurotrophic Keratitis: Do Not Be Insensitive},
	journal = {Eye Contact Lens},
	volume = {47},
	number = {3},
	year = {2021},
	month = {2021 Mar 01},
	pages = {135},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000778},
	author = {Jhanji, Vishal and Jacobs, Deborah S and Jeng, Bennie H}
}
@article {1647877,
	title = {Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema},
	journal = {N Engl J Med},
	year = {2022},
	month = {2022 Jul 14},
	abstract = {BACKGROUND: In eyes with diabetic macular edema, the relative efficacy of administering aflibercept monotherapy as compared with bevacizumab first with a switch to aflibercept if the eye condition does not improve sufficiently (a form of step therapy) is unclear. METHODS: At 54 clinical sites, we randomly assigned eyes in adults who had diabetic macular edema involving the macular center and a visual-acuity letter score of 24 to 69 (on a scale from 0 to 100, with higher scores indicating better visual acuity; Snellen equivalent, 20/320 to 20/50) to receive either 2.0 mg of intravitreous aflibercept or 1.25 mg of intravitreous bevacizumab. The drug was administered at randomization and thereafter according to the prespecified retreatment protocol. Beginning at 12 weeks, eyes in the bevacizumab-first group were switched to aflibercept therapy if protocol-specified criteria were met. The primary outcome was the mean change in visual acuity over the 2-year trial period. Retinal central subfield thickness and visual acuity at 2 years and safety were also assessed. RESULTS: A total of 312 eyes (in 270 adults) underwent randomization; 158 eyes were assigned to receive aflibercept monotherapy and 154 to receive bevacizumab first. Over the 2-year period, 70\% of the eyes in the bevacizumab-first group were switched to aflibercept therapy. The mean improvement in visual acuity was 15.0 letters in the aflibercept-monotherapy group and 14.0 letters in the bevacizumab-first group (adjusted difference, 0.8 letters; 95\% confidence interval, -0.9 to 2.5; P = 0.37). At 2 years, the mean changes in visual acuity and retinal central subfield thickness were similar in the two groups. Serious adverse events (in 52\% of the patients in the aflibercept-monotherapy group and in 36\% of those in the bevacizumab-first group) and hospitalizations for adverse events (in 48\% and 32\%, respectively) were more common in the aflibercept-monotherapy group. CONCLUSIONS: In this trial of treatment of moderate vision loss due to diabetic macular edema involving the center of the macula, we found no evidence of a significant difference in visual outcomes over a 2-year period between aflibercept monotherapy and treatment with bevacizumab first with a switch to aflibercept in the case of suboptimal response. (Funded by the National Institutes of Health; Protocol AC ClinicalTrials.gov number, NCT03321513.).},
	issn = {1533-4406},
	doi = {10.1056/NEJMoa2204225},
	author = {Jhaveri, Chirag D and Glassman, Adam R and Ferris, Frederick L and Liu, Danni and Maguire, Maureen G and Allen, John B and Baker, Carl W and Browning, David and Cunningham, Matthew A and Friedman, Scott M and Jampol, Lee M and Marcus, Dennis M and Martin, Daniel F and Preston, Carin M and Stockdale, Cynthia R and Sun, Jennifer K and DRCR Retina Network}
}
@article {1586142,
	title = {Visual acuity and progression of macular atrophy in patients receiving intravitreal anti-VEGF for age-related macular degeneration},
	journal = {Eur J Ophthalmol},
	volume = {32},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {429-435},
	abstract = {PURPOSE: Whether intravitreal anti-vascular endothelial growth factors (VEGFs) cause retinal atrophy is still a subject of debate. We reported 13 eyes that received several injections of anti-VEGF for wet age-related macular degeneration (AMD) with good visual acuity despite geographic atrophy on imaging. METHODS: This is a case series study conducted at Byers Eye Institute at Stanford University. Patients of three retina specialists with wet AMD who received six or more intravitreal injection of anti-VEGFs with visual acuity of 20/60 or better and incomplete RPE and outer retina atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA) were enrolled in this case series. Different imaging modalities were reviewed by three retina specialists comparing the baseline with the most recent exam. RESULTS: About 13 eyes of 10 patients met the selection criteria. Eleven eyes were classified as iRORA and 2 as cRORA. Despite the development of macular atrophy on imaging after an average of 38.1 injections, eyes maintained stable visual acuity. CONCLUSION: The discrepancy between structural and functional findings in this cohort suggests that patients treated by anti-VEGF drugs exhibit divergent clinical outcomes for currently unknown reasons. The authors propose anti-VEGF may affect melanosomes within RPE without disrupting RPE and photoreceptors function completely. This requires further investigation.},
	keywords = {Angiogenesis Inhibitors, Atrophy, Humans, Intravitreal Injections, Ranibizumab, Tomography, Optical Coherence, Vascular Endothelial Growth Factors, Visual Acuity, Wet Macular Degeneration},
	issn = {1724-6016},
	doi = {10.1177/11206721211001708},
	author = {Ji, Marco H and Callaway, Natalia F and Ludwig, Cassie A and Vail, Daniel and Al-Moujahed, Ahmad and Rosenblatt, Tatiana R and Leng, Theodore and Sanislo, Steven R and Moshfeghi, Darius M}
}
@article {987986,
	title = {Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation},
	journal = {Mucosal Immunol},
	volume = {10},
	number = {5},
	year = {2017},
	month = {2017 Sep},
	pages = {1202-1210},
	abstract = {Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.},
	issn = {1935-3456},
	doi = {10.1038/mi.2016.119},
	author = {Ji, Y W and Mittal, S K and Hwang, H S and Chang, E-J and Lee, J H and Seo, Y and Yeo, A and Noh, H and Lee, H S and Chauhan, S K and Lee, H K}
}
@article {1538354,
	title = {A Review of New Medications and Future Directions of Medical Therapies in Glaucoma},
	journal = {Semin Ophthalmol},
	year = {2020},
	month = {2020 Oct 05},
	pages = {1-7},
	abstract = {BACKGROUND: Glaucoma is one of the leading causes of blindness worldwide. Treatment is still largely targeted at lowering intraocular pressure. Intraocular pressures can be lowered through a variety of topical medications, lasers and incisional surgeries. There are currently several classes of topical medications available in the US that are aimed at lowering intraocular pressure through a variety of different mechanisms. Additionally, there have been numerous different formulations and fixed-dose combination medications that offer greatly expanded treatment options over the last several years. The wide variety of topical medications aim to address the issues with compliance, effectiveness and side effect profile that vary among each individual patient and disease.\&nbsp; Purpose: Three new topical medications, netarsudil 0.02\%, latanoprostene bunod 0.24\% and fixed-dose combination netarsudil 0.02\% - latanoprost 0.005\% have been approved in the US market to treat glaucoma. This review article will summarize the studies looking at their effectiveness and side effect profiles and discuss their utilization in the treatment of glaucoma. Additionally, we will briefly discuss future directions of research in topical glaucoma medications. CONCLUSION: Three new topical glaucoma medications offer additional treatment options for patient with glaucoma. Further research is needed to better understand the utility of sustained release formulations in the treatment of glaucoma.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1818796},
	author = {Jiang, Ying and Ondeck, Courtney}
}
@article {630296,
	title = {Transient Tear Film Dysfunction after Cataract Surgery in Diabetic Patients.},
	journal = {PLoS One},
	volume = {11},
	number = {1},
	year = {2016},
	month = {2016},
	pages = {e0146752},
	abstract = {PURPOSE: Diabetes mellitus is an increasingly common systemic disease. Many diabetic patients seek cataract surgery for a better visual acuity. Unlike in the general population, the influence of cataract surgery on tear film function in diabetic patients remains elusive. The aim of this study was to evaluate the tear function in diabetic and nondiabetic patients following cataract surgery. METHODS: In this prospective, interventional case series, 174 diabetic patients without dry eye syndrome (DES) and 474 age-matched nondiabetic patients as control who underwent phacoemulsification were enrolled at two different eye centers between January 2011 and January 2013. Patients were followed up at baseline and at 7 days, 1 month, and 3 months postoperatively. Ocular symptom scores (Ocular Surface Disease Index, OSDI) and tear film function including tear film stability (tear film break-up time, TBUT), corneal epithelium integrity (corneal fluorescein staining, CFS), and tear secretion (Schirmer{\textquoteright}s I test, SIT) were evaluated. RESULTS: In total, 83.9\% of the diabetic patients (146 cases with 185 eyes) and 89.0\% of the nondiabetic patients (422 cases with 463 eyes) completed all check-ups after the interventions (P = 0.095). The incidence of DES was 17.1\% in the diabetic patients and 8.1\% in the nondiabetic patients at 7 days after cataract surgery. In the diabetic patients, the incidence of DES remained 4.8\% at 1 month postoperatively and decreased to zero at 3 months after surgery. No DES was diagnosed in nondiabetic patients at either the 1-month or 3-month follow-up. Compared with the baseline, the diabetic patients had worse symptom scores and lower TBUT values at 7 days and 1 month but not at 3 months postoperatively. In the nondiabetic patients, symptom scores and TBUT values had returned to preoperative levels at 1-month check-up. CFS scores and SIT values did not change significantly postoperatively in either group (P = 0.916 and P = 0.964, respectively). CONCLUSIONS: Diabetic patients undergoing cataract surgery are prone to DES. Ocular symptoms and tear film stability are transiently worsened in diabetic patients and are restored more slowly than those in nondiabetic patients.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0146752},
	author = {Jiang, Donghong and Xiao, Xiangqian and Fu, Tongsheng and Mashaghi, Alireza and Liu, Qinghuai and Hong, Jiaxu}
}
@article {1424805,
	title = {APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION: Results of a Prospective Trial. Report No. 2},
	journal = {Retina},
	volume = {39},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {265-273},
	abstract = {PURPOSE: We sought to characterize the angiofibrotic and apoptotic effects of vascular endothelial growth factor (VEGF)-inhibition on fibrovascular epiretinal membranes in eyes with traction retinal detachment because of proliferative diabetic retinopathy. METHODS: Membranes were excised from 20 eyes of 19 patients (10 randomized to intravitreal bevacizumab, 10 controls) at vitrectomy. Membranes were stained with antibodies targeting connective tissue growth factor (CTGF) or VEGF and colabeled with antibodies directed against endothelial cells (CD31), myofibroblasts, or retinal pigment epithelium markers. Quantitative and colocalization analyses of antibody labeling were obtained through immunofluorescence confocal microscopy. Masson trichrome staining, cell counting of hematoxylin and eosin sections, and terminal dUTP nick-end labeling staining were performed. RESULTS: High levels of fibrosis were observed in both groups. Cell apoptosis was higher (P = 0.05) in bevacizumab-treated membranes compared with controls. The bevacizumab group had a nonsignificant reduction in colocalization in CD31-CTGF and cytokeratin-VEGF studies compared with controls. Vascular endothelial growth factor in extracted membranes was positively correlated with vitreous levels of VEGF; CTGF in extracted membranes was negatively correlated with vitreous levels of CTGF. CONCLUSION: Bevacizumab suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF in diabetic membranes that may be explained by high baseline levels of fibrosis. Bevacizumab may cause apoptosis within fibrovascular membranes.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001952},
	author = {Jiao, Chunhua and Eliott, Dean and Spee, Christine and He, Shikun and Kai Wang and Mullins, Robert F and Hinton, David R and Sohn, Elliott H}
}
@article {1043236,
	title = {Dacryoadenitis as the Initial Presentation of a Natural Killer T-Cell Lymphoma},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {33},
	number = {6},
	year = {2017},
	month = {2017 Nov/Dec},
	pages = {e147-e150},
	abstract = {Primary orbital natural killer T-cell lymphoma (NKTCL) is a rare condition with only a few published cases in the literature. Over 1 month, an 81-year-old man developed progressive left periocular inflammation unresponsive to treatment. Clinical examination and imaging studies demonstrated a left lacrimal gland enlargement. Bilateral anterior uveitis and erythematous nontender cutaneous lesions were also found. Biopsies of the skin and lacrimal gland on the back revealed histopathologic and immunohistochemical findings confirming Epstein-Barr virus-positive NKTCL. Metastatic work up disclosed multifocal involvement in the pancreas, stomach, and chest wall. Palliative treatment consisting of nonanthracycline-based chemotherapy and radiation was instituted, but the patient died 5 months after the onset of symptoms. This is the first example of acute dacryoadenitis, and the second of bilateral anterior uveitis, in the setting of NKTCL. Absence of naso-sinus involvement in the current case is rare in NKTCL. Despite treatment, the prognosis remains dismal. Orbital specialists should include NKTCL in the differential diagnosis of lacrimal gland/orbital masses and perform an incisional biopsy if the clinical scenario so dictates.},
	keywords = {Aged, 80 and over, Biopsy, Dacryocystitis, Diagnosis, Differential, Fatal Outcome, Humans, Lacrimal Apparatus, Lymphoma, Extranodal NK-T-Cell, Male, Orbit, Orbital Neoplasms, Tomography, X-Ray Computed},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000889},
	author = {Jim{\'e}nez-P{\'e}rez, Juan C and Jakobiec, Frederick A and Zakka, Fouad R and Yoon, Michael K}
}
@article {1645457,
	title = {Ang Ating Mata: Disparities in Eye Health Knowledge, Attitudes and Practices among Older Adult Filipino-Americans in the San Francisco Bay Area Counties},
	journal = {J Immigr Minor Health},
	volume = {25},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {104-114},
	abstract = {Filipino-Americans are the third largest Asian-American population, with a median age of 44. However, there is limited literature focusing on the group{\textquoteright}s ophthalmic care engagement. Timely eye examinations and outreach are necessary to reduce visual impairment in this older community. To assess eye care knowledge, attitudes, and practices, we conducted a cross-sectional study surveying Filipino-Americans within the nine San Francisco Bay Area counties. Associations between primary outcomes and sociodemographic factors were analyzed using chi-squared analysis and student{\textquoteright}s T-test. In our convenience sample of 256 surveys, a majority of participants are receiving appropriate eye care; those that lacked health and eye insurance, immigrated and are lower income did not receive optimal eye care. Study participants also demonstrated a lack of awareness of eye diseases and risk factors. Our results suggest that culturally sensitive eye health education materials are lacking and should be made accessible for this large and rapidly growing population.},
	keywords = {Aged, Asian, Cross-Sectional Studies, Eye Diseases, Health Knowledge, Attitudes, Practice, Humans, San Francisco},
	issn = {1557-1920},
	doi = {10.1007/s10903-022-01371-3},
	author = {Jiro, Marycon Chin and Sigua, Michael and Ivey, Susan L and Maus, Marlon and Hennein, Lauren and Dio, Migel and Cocohoba, Jennifer}
}
@article {1688316,
	title = {The importance of unambiguous cell origin determination in neuronal repopulation studies},
	journal = {iScience},
	volume = {26},
	number = {4},
	year = {2023},
	month = {2023 Apr 21},
	pages = {106361},
	abstract = {Neuronal repopulation achieved through transplantation or transdifferentiation from endogenous sources holds tremendous potential for restoring function in chronic neurodegenerative disease or acute injury. Key to the evaluation of neuronal engraftment is the definitive discrimination of new or donor neurons from preexisting cells within the host tissue. Recent work has identified mechanisms by which genetically encoded donor cell reporters can be transferred to host neurons through intercellular material transfer. In addition, labeling transplanted and endogenously transdifferentiated neurons through viral vector transduction can yield misexpression in host cells in some circumstances. These issues can confound the tracking and evaluation of repopulated neurons in regenerative experimental paradigms. Using the retina as an example, we discuss common reasons for artifactual labeling of endogenous host neurons with donor cell reporters and suggest strategies to prevent erroneous conclusions based on misidentification of cell origin.},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2023.106361},
	author = {Johnson, Thomas V and Calkins, David J and Fortune, Brad and Goldberg, Jeffrey L and Torre, Anna La and Lamba, Deepak A and Meyer, Jason S and Reh, Thomas A and Wallace, Valerie A and Zack, Donald J and Baranov, Petr}
}
@article {1789026,
	title = {The Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration Consortium},
	journal = {Ophthalmol Sci},
	volume = {3},
	number = {4},
	year = {2023},
	month = {2023 Dec},
	pages = {100390},
	abstract = {PURPOSE: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators. DESIGN AND PARTICIPANTS: The RReSTORe consortium currently includes \&gt; 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds. METHODS: Herein, we describe the structure and organization of the RReSTORe consortium, its activities to date, and the perceived impact that the consortium has had on the field based on a survey of participants. RESULTS: In addition to helping propel the field of regenerative medicine as applied to optic neuropathies, the RReSTORe consortium serves as a framework for developing large collaborative groups aimed at tackling audacious goals that may be expanded beyond ophthalmology and vision science. CONCLUSIONS: The development of innovative interventions capable of restoring vision for patients suffering from optic neuropathy would be transformative for the ophthalmology field, and may set the stage for functional restoration in other central nervous system disorders. By coordinating large-scale, international collaborations among scientists with diverse and complementary expertise, we are confident that the RReSTORe consortium will help to accelerate the field toward clinical translation. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found\&nbsp;in the Footnotes and Disclosures at the end of this article.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100390},
	author = {Johnson, Thomas V and Baranov, Petr and Di Polo, Adriana and Fortune, Brad and Gokoffski, Kimberly K and Goldberg, Jeffrey L and Guido, William and Kolodkin, Alex L and Mason, Carol A and Ou, Yvonne and Reh, Thomas A and Ross, Ahmara G and Samuels, Brian C and Zack, Donald J}
}
@article {1109826,
	title = {Systematic genomic and translational efficiency studies of uveal melanoma},
	journal = {PLoS One},
	volume = {12},
	number = {6},
	year = {2017},
	month = {2017},
	pages = {e0178189},
	abstract = {To further our understanding of the somatic genetic basis of uveal melanoma, we sequenced the protein-coding regions of 52 primary tumors and 3 liver metastases together with paired normal DNA. Known recurrent mutations were identified in GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. The role of mutated EIF1AX was tested using loss of function approaches including viability and translational efficiency assays. Knockdown of both wild type and mutant EIF1AX was lethal to uveal melanoma cells. We probed the function of N-terminal tail EIF1AX mutations by performing RNA sequencing of polysome-associated transcripts in cells expressing endogenous wild type or mutant EIF1AX. Ribosome occupancy of the global translational apparatus was sensitive to suppression of wild type but not mutant EIF1AX. Together, these studies suggest that cells expressing mutant EIF1AX may exhibit aberrant translational regulation, which may provide clonal selective advantage in the subset of uveal melanoma that harbors this mutation.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0178189},
	author = {Johnson, Chelsea Place and Kim, Ivana K and Esmaeli, Bita and Amin-Mansour, Ali and Treacy, Daniel J and Carter, Scott L and Hodis, Eran and Wagle, Nikhil and Seepo, Sara and Yu, Xiaoxing and Lane, Anne Marie and Gragoudas, Evangelos S and Vazquez, Francisca and Nickerson, Elizabeth and Cibulskis, Kristian and McKenna, Aaron and Gabriel, Stacey B and Getz, Gad and Van Allen, Eliezer M and {\textquoteright}t Hoen, Peter A C and Garraway, Levi A and Woodman, Scott E}
}
@article {1318864,
	title = {Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin-resistant Staphylococcus aureus},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 May 04},
	pages = {7062},
	abstract = {The emergence of Staphylococcus aureus strains resistant to {\textquoteright}last resort{\textquoteright} antibiotics compels the development of new antimicrobials against this important human pathogen. We found that propyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) shows bacteriostatic activity against S. aureus (MIC = 4 μg/ml) and rescues Caenorhabditis elegans from S. aureus infection. Whole-genome sequencing of S. aureus mutants resistant to the compound, along with screening of a S. aureus promoter-lux reporter array, were used to explore possible mechanisms of action. All mutants resistant to HMPC acquired missense mutations at distinct codon positions in the global transcriptional regulator mgrA, followed by secondary mutations in the phosphatidylglycerol lysyltransferase fmtC/mprF. The S. aureus promoter-lux array treated with HMPC displayed a luminescence profile that was unique but showed similarity to DNA-damaging agents and/or DNA replication inhibitors. Overall, HMPC is a new anti-staphylococcal compound that appears to act via an unknown mechanism linked to the global transcriptional regulator MgrA.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-25571-w},
	author = {Johnston, Tatiana and Van Tyne, Daria and Chen, Roy F and Fawzi, Nicolas L and Kwon, Bumsup and Kelso, Michael J and Gilmore, Michael S and Mylonakis, Eleftherios}
}
@article {1478320,
	title = {Mystery Eye: Human Adenovirus and the Enigma of Epidemic Keratoconjunctivitis},
	journal = {Prog Retin Eye Res},
	year = {2019},
	month = {2019 Dec 28},
	pages = {100826},
	abstract = {Known to occur in widespread outbreaks, epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection with a strong historical association with human adenovirus (HAdV). While the conjunctival manifestations can vary from mild follicular conjunctivitis to hyper-acute, exudative conjunctivitis with formation of conjunctival membranes, EKC is distinct as the only form of adenovirus conjunctivitis in which the cornea is also involved, likely due to specific corneal epithelial tropism of its causative viral agents. The initial development of a punctate or geographic epithelial keratitis may herald the later formation of stromal keratitis, and manifest as subepithelial infiltrates which often persist or recur for months to years after the acute infection has resolved. The chronic keratitis in EKC is associated with foreign body sensation, photophobia, glare, and reduced vision. However, over a century since the first clinical descriptions of EKC, and over 60 years since the first causative agent, human adenovirus type 8, was identified, our understanding of this disorder remains limited. This is underscored by a current lack of effective diagnostic tools and treatments. In part, stasis in our knowledge base has been encouraged by the continued acceptance, and indeed propagation of, inaccurate paradigms pertaining to disease etiology and pathogenesis, particularly with regard to mechanisms of innate and adaptive immunity within the cornea. Owing to its often persistent and medically refractory visual sequelae, reconsideration of key aspects of EKC disease biology is warranted to identify new treatment targets to curb its worldwide socioeconomic burden.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2019.100826},
	author = {Jonas, Rahul A and Ung, Lawson and Rajaiya, Jaya and Chodosh, James}
}
@article {1698311,
	title = {TFOS lifestyle: Impact of contact lenses on the ocular surface},
	journal = {Ocul Surf},
	year = {2023},
	month = {2023 May 04},
	abstract = {Several lifestyle choices made by contact lens wearers can have adverse consequences on ocular health. These include being non-adherent to contact lens care, sleeping in lenses, ill-advised purchasing options, not seeing an eyecare professional for regular aftercare visits, wearing lenses when feeling unwell, wearing lenses too soon after various forms of ophthalmic surgery, and wearing lenses when engaged in risky behaviours (e.g., using tobacco, alcohol or recreational drugs). Those with a pre-existing compromised ocular surface may find that contact lens wear exacerbates ocular disease morbidity. Conversely, contact lenses may have various therapeutic benefits. The coronavirus disease-2019 (COVID-19) pandemic has impinged upon the lifestyle of contact lens wearers, introducing challenges such as mask-associated dry eye, contact lens discomfort with increased use of digital devices, inadvertent exposure to hand sanitizers, and reduced use of lenses. Wearing contact lenses in challenging environments, such as in the presence of dust and noxious chemicals, or where there is the possibility of ocular trauma (e.g., sport or working with tools) can be problematic, although in some instances lenses can be protective. Contact lenses can be worn for sport, theatre, at high altitude, driving at night, in the military and in space, and special considerations are required when prescribing in such situations to ensure successful outcomes. A systematic review and meta-analysis, incorporated within the review, identified that the influence of lifestyle factors on soft contact lens dropout remains poorly understood, and is an area in need of further research. Overall, this report investigated lifestyle-related choices made by clinicians and contact lens wearers and discovered that when appropriate lifestyle choices are made, contact lens wear can enhance the quality of life of wearers.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2023.04.010},
	author = {Jones, Lyndon and Efron, Nathan and Bandamwar, Kalika and Barnett, Melissa and Jacobs, Deborah S and Jalbert, Isabelle and Pult, Heiko and Rhee, Michelle K and Sheardown, Heather and Shovlin, Joseph P and Stahl, Ulli and Stanila, Adriana and Tan, Jacqueline and Tavazzi, Silvia and Ucakhan, Omur O and Willcox, Mark D P and Downie, Laura E}
}
@article {1586155,
	title = {CLEAR - Contact lens technologies of the future},
	journal = {Cont Lens Anterior Eye},
	volume = {44},
	number = {2},
	year = {2021},
	month = {2021 Apr},
	pages = {398-430},
	abstract = {Contact lenses in the future will likely have functions other than correction of refractive error. Lenses designed to control the development of myopia are already commercially available. Contact lenses as drug delivery devices and powered through advancements in nanotechnology will open up further opportunities for unique uses of contact lenses. This review examines the use, or potential use, of contact lenses aside from their role to correct refractive error. Contact lenses can be used to detect systemic and ocular surface diseases, treat and manage various ocular conditions and as devices that can correct presbyopia, control the development of myopia or be used for augmented vision. There is also discussion of new developments in contact lens packaging and storage cases. The use of contact lenses as devices to detect systemic disease has mostly focussed on detecting changes to glucose levels in tears for monitoring diabetic control. Glucose can be detected using changes in colour, fluorescence or generation of electric signals by embedded sensors such as boronic acid, concanavalin A or glucose oxidase. Contact lenses that have gained regulatory approval can measure changes in intraocular pressure to monitor glaucoma by measuring small changes in corneal shape. Challenges include integrating sensors into contact lenses and detecting the signals generated. Various techniques are used to optimise uptake and release of the drugs to the ocular surface to treat diseases such as dry eye, glaucoma, infection and allergy. Contact lenses that either mechanically or electronically change their shape are being investigated for the management of presbyopia. Contact lenses that slow the development of myopia are based upon incorporating concentric rings of plus power, peripheral optical zone(s) with add power or non-monotonic variations in power. Various forms of these lenses have shown a reduction in myopia in clinical trials and are available in various markets.},
	issn = {1476-5411},
	doi = {10.1016/j.clae.2021.02.007},
	author = {Jones, Lyndon and Hui, Alex and Phan, Chau-Minh and Read, Michael L and Azar, Dimitri and Buch, John and Ciolino, Joseph B and Naroo, Shehzad A and Pall, Brian and Romond, Kathleen and Sankaridurg, Padmaja and Schnider, Cristina M and Terry, Louise and Willcox, Mark}
}
@article {1125326,
	title = {TFOS DEWS II Management and Therapy Report},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {575-628},
	abstract = {The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.05.006},
	author = {Jones, Lyndon and Downie, Laura E and Korb, Donald and Benitez-Del-Castillo, Jose M and Dana, Reza and Deng, Sophie X and Dong, Pham N and Geerling, Gerd and Hida, Richard Yudi and Liu, Yang and Seo, Kyoung Yul and Tauber, Joseph and Wakamatsu, Tais H and Xu, Jianjiang and Wolffsohn, James S and Craig, Jennifer P}
}
@article {1402579,
	title = {Hydroxychloroquine retinopathy - implications of research advances for rheumatology care},
	journal = {Nat Rev Rheumatol},
	volume = {14},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {693-703},
	abstract = {Despite advances in therapy for rheumatic diseases, hydroxychloroquine remains almost universally recommended for the treatment of systemic lupus erythematosus (SLE), and is\&nbsp;often used in the management of other rheumatic diseases such as rheumatoid arthritis (RA). However, the major dose-limiting toxicity of hydroxychloroquine is retinopathy that can lead to loss of vision. New highly sensitive screening methods can identify early stages of retinopathy, and studies that include these modalities have indicated a substantially higher prevalence of hydroxychloroquine retinopathy than was previously recognized, resulting in revisions to ophthalmology guidelines and the recommendation of a low dose of hydroxychloroquine for many patients. However, the efficacy of low-dose hydroxychloroquine for treating SLE and other\&nbsp;rheumatic diseases is unknown. Further studies are required to establish the effectiveness and retinal safety of the latest hydroxychloroquine treatment recommendations.},
	issn = {1759-4804},
	doi = {10.1038/s41584-018-0111-8},
	author = {Jorge, April and Ung, Cindy and Young, Lucy H and Melles, Ronald B and Choi, Hyon K}
}
@article {1323931,
	title = {Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthalmology guidelines},
	journal = {Arthritis Res Ther},
	volume = {20},
	number = {1},
	year = {2018},
	month = {2018 Jul 05},
	pages = {133},
	abstract = {BACKGROUND: Hydroxychloroquine (HCQ) retinopathy may be more common than previously recognized; recent ophthalmology guidelines have revised recommendations from ideal body weight (IBW)-based dosing to actual body weight (ABW)-based dosing. However, contemporary HCQ prescribing trends in the UK remain unknown. METHODS: We examined a UK general population database to investigate HCQ dosing between 2007 and 2016. We studied trends of excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5\&nbsp;mg/kg of IBW and 5.0\&nbsp;mg/kg of ABW) and determined their independent predictors using multivariable logistic regression analyses. RESULTS: Among 20,933 new HCQ users (78\% female), the proportions of initial HCQ excess dosing declined from 40\% to 36\% using IBW and 38\% to 30\% using ABW, between 2007 and 2016. Among these, 47\% of women were excess-dosed (multivariable OR 12.52; 95\% CI 10.99-14.26) using IBW and 38\% (multivariable OR 1.98; 95\% CI,1.81-2.15) using ABW. Applying IBW, 37\% of normal and 44\% of obese patients were excess-dosed; however, applying ABW, 53\% of normal and 10\% of obese patients were excess-dosed (multivariable ORs = 1.61 and 0.1 (reference = normal); both p \&lt; 0.01). Long-term HCQ users showed similar excess dosing. CONCLUSION: A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years. Over half of normal-BMI individuals were excess-dosed per the latest guidelines. This implies the potential need to reduce dosing for many patients but also calls for further research to establish unifying evidence-based safe and effective dosing strategies.},
	issn = {1478-6362},
	doi = {10.1186/s13075-018-1634-8},
	author = {Jorge, April M and Melles, Ronald B and Zhang, Yuqing and Lu, Na and Rai, Sharan K and Young, Lucy H and Costenbader, Karen H and Ramsey-Goldman, Rosalind and Lim, S Sam and Esdaile, John M and Clarke, Ann E and Urowitz, M B and Askanase, Anca and Aranow, Cynthia and Petri, Michelle and Choi, Hyon}
}
@article {1647900,
	title = {Validation of diagnostic accuracy of retinal image grading by trained non-ophthalmologist grader for detecting diabetic retinopathy and diabetic macular edema},
	journal = {Eye (Lond)},
	volume = {37},
	number = {8},
	year = {2023},
	month = {2023 Jun},
	pages = {1577-1582},
	abstract = {PURPOSE: To validate the fundus image grading results by a trained grader (Non-ophthalmologist) and an ophthalmologist grader for detecting diabetic retinopathy (DR) and diabetic macular oedema (DMO) against fundus examination by a retina specialist (gold standard). METHODS: A prospective diagnostic accuracy study was conducted using 2002 non-mydriatic colour fundus images from 1001 patients aged >=40 years. Using the Aravind Diabetic Retinopathy Evaluation Software (ADRES) images were graded by both a trained non-ophthalmologist grader (grader-1) and an ophthalmologist (grader-2). Sensitivity, specificity, positive predictive value and negative predictive value were calculated for grader-1 and grader-2 against the grading results by an independent retina specialist who performed dilated fundus examination for every study participant. RESULTS: Out of 1001 patients included, 42\% were women and the mean {\textpm} (SD) age was 55.8 (8.39) years. For moderate or worse DR, the sensitivity and specificity for grading by grader-1 with respect to the gold standard was 66.9\% and 91.0\% respectively and the same for the ophthalmologist was 83.6\% and 80.3\% respectively. For referable DMO, grader-1 and grader-2 had a sensitivity of 74.6\% and 85.6\% respectively and a specificity of 83.7\% and 79.8\% respectively. CONCLUSIONS: Our results demonstrate good level of accuracy for the fundus image grading performed by a trained non-ophthalmologist which was comparable with the grading by an ophthalmologist. Engaging trained non-ophthalmologists potentially can enhance the efficiency of DR diagnosis using fundus images. Further study with multiple non-ophthalmologist graders is needed to verify the results and strategies to improve agreement for DMO diagnosis are needed.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Female, Humans, Macular Edema, Male, Photography, Prospective Studies, Retina, Sensitivity and Specificity},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-02190-4},
	author = {Joseph, Sanil and Rajan, Renu P and Sundar, Balagiri and Venkatachalam, Soundarya and Kempen, John H and Kim, Ramasamy}
}
@article {1598055,
	title = {Investigation of the Accuracy of a Low-Cost, Portable Autorefractor to Provide Well-Tolerated Eyeglass Prescriptions: A Randomized Crossover Trial},
	journal = {Ophthalmology},
	volume = {128},
	number = {12},
	year = {2021},
	month = {2021 12},
	pages = {1672-1680},
	abstract = {PURPOSE: To compare patient preferences for eyeglasses prescribed using a low-cost, portable wavefront autorefractor versus standard subjective refraction (SR). DESIGN: Randomized, cross-over clinical trial. PARTICIPANTS: Patients aged 18 to 40 years presenting with refractive errors (REs) to a tertiary eye hospital in Southern India. METHODS: Participants underwent SR followed by autorefraction (AR) using the monocular version of the QuickSee device (PlenOptika Inc). An independent optician, masked to the refraction approach, prepared eyeglasses based on each refraction approach. Participants (masked to refraction source) were randomly assigned to use SR- or AR-based eyeglasses first, followed by the other pair, for 1 week each. At the end of each week, participants had their vision checked and were interviewed about their experience with the eyeglasses. MAIN OUTCOME MEASURES: Patients preferring eyeglasses were chosen using AR and SR. RESULTS: The 400 participants enrolled between March 26, 2018, and August 2, 2019, had a mean (standard deviation) age of 28.4 (6.6) years, and 68.8\% were women. There was a strong correlation between spherical equivalents using SR and AR (r\&nbsp;= 0.97, P \&lt; 0.001) with a mean difference of\&nbsp;-0.07 diopters (D) (95\% limits of agreement [LoA],\&nbsp;-0.68 to 0.83). Of the 301 patients (75.2\%) who completed both follow-up visits, 50.5\% (n\&nbsp;=\&nbsp;152) and 49.5\% (n\&nbsp;= 149) preferred glasses prescribed using SR and AR, respectively (95\% CI, 45.7-56.3; P\&nbsp;= 0.86). There were no differences in demographic or vision characteristics between participants with different preferences (P \&gt; 0.05 for all). CONCLUSIONS: We observed a strong agreement between the prescriptions from SR and AR, and eyeglasses prescribed using SR and AR were equally preferred by patients. Wider use of prescribing based on AR alone in resource-limited settings is supported by these findings.},
	keywords = {Adolescent, Adult, Cross-Over Studies, Double-Blind Method, Eyeglasses, Female, Humans, Male, Patient Acceptance of Health Care, Prescriptions, Refraction, Ocular, Refractive Errors, Reproducibility of Results, Retinoscopy, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.05.030},
	author = {Joseph, Sanil and Varadaraj, Varshini and Dave, Shivang R and Lage, Eduardo and Lim, Daryl and Aziz, Kanza and Dudgeon, Sarah and Ravilla, Thulasiraj D and Friedman, David S}
}
@article {935681,
	title = {Attributes Associated with Adherence to Glaucoma Medical Therapy and its Effects on Glaucoma Outcomes: An Evidence-Based Review and Potential Strategies to Improve Adherence.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	pages = {86-90},
	abstract = {The treatment paradigm in glaucoma classically starts with exhausting all medical therapy prior to proceeding with laser or incisional surgery, although laser-first and surgery-first strategies have been explored in randomized clinical trials. Although glaucoma drops are proven to work well to lower intraocular pressure, slow the conversion from ocular hypertension, and slow the progression of disease in early open angle glaucoma, adherence to treatment is likely optimum in the randomized clinical trials that support these claims. In real-world scenarios, medical therapy often fails and practitioners are forced to proceed with more invasive treatment modalities to slow the progression of this blinding disease. This review aims to take an evidence-based approach to study the risk factors for poor adherence in glaucoma patients, to determine whether poor adherence is, in fact, associated with worse outcomes, and to seek potential strategies to improve adherence in these patients.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228406},
	author = {Joseph, Arun and Pasquale, Louis R}
}
@article {504086,
	title = {Directional dominance on stature and cognition indiverse human populations.},
	journal = {Nature},
	volume = {523},
	number = {7561},
	year = {2015},
	month = {2015 Jul 23},
	pages = {459-62},
	abstract = {Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs\&nbsp;of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P \&lt; 1 {\texttimes} 10(-300), 2.1 {\texttimes} 10(-6), 2.5 {\texttimes} 10(-10) and 1.8 {\texttimes} 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months{\textquoteright} less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.},
	keywords = {Biological Evolution, Blood Pressure, Body Height, Cholesterol, LDL, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume, Genome, Human, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype},
	issn = {1476-4687},
	doi = {10.1038/nature14618},
	author = {Joshi, Peter K and Esko, Tonu and Mattsson, Hannele and Eklund, Niina and Gandin, Ilaria and Nutile, Teresa and Jackson, Anne U and Schurmann, Claudia and Smith, Albert V and Zhang, Weihua and Okada, Yukinori and Stan{\v c}{\'a}kov{\'a}, Alena and Faul, Jessica D and Zhao, Wei and Bartz, Traci M and Concas, Maria Pina and Franceschini, Nora and Enroth, Stefan and Vitart, Veronique and Trompet, Stella and Guo, Xiuqing and Chasman, Daniel I and O{\textquoteright}Connel, Jeffrey R and Corre, Tanguy and Nongmaithem, Suraj S and Chen, Yuning and Mangino, Massimo and Ruggiero, Daniela and Traglia, Michela and Farmaki, Aliki-Eleni and Kacprowski, Tim and Bjonnes, Andrew and van der Spek, Ashley and Wu, Ying and Giri, Anil K and Yanek, Lisa R and Wang, Lihua and Hofer, Edith and Rietveld, Cornelius A and McLeod, Olga and Cornelis, Marilyn C and Pattaro, Cristian and Verweij, Niek and Baumbach, Clemens and Abdellaoui, Abdel and Warren, Helen R and Vuckovic, Dragana and Mei, Hao and Bouchard, Claude and Perry, John R B and Cappellani, Stefania and Mirza, Saira S and Benton, Miles C and Broeckel, Ulrich and Medland, Sarah E and Lind, Penelope A and Malerba, Giovanni and Drong, Alexander and Yengo, Loic and Bielak, Lawrence F and Zhi, Degui and van der Most, Peter J and Shriner, Daniel and M{\"a}gi, Reedik and Hemani, Gibran and Karaderi, Tugce and Wang, Zhaoming and Liu, Tian and Demuth, Ilja and Zhao, Jing Hua and Meng, Weihua and Lataniotis, Lazaros and van der Laan, Sander W and Bradfield, Jonathan P and Wood, Andrew R and Bonnefond, Amelie and Ahluwalia, Tarunveer S and Hall, Leanne M and Salvi, Erika and Yazar, Seyhan and Carstensen, Lisbeth and de Haan, Hugoline G and Abney, Mark and Afzal, Uzma and Allison, Matthew A and Amin, Najaf and Asselbergs, Folkert W and Bakker, Stephan J L and Barr, R Graham and Baumeister, Sebastian E and Benjamin, Daniel J and Bergmann, Sven and Boerwinkle, Eric and Bottinger, Erwin P and Campbell, Archie and Chakravarti, Aravinda and Chan, Yingleong and Chanock, Stephen J and Chen, Constance and Chen, Y-D Ida and Collins, Francis S and Connell, John and Correa, Adolfo and Cupples, L Adrienne and Smith, George Davey and Davies, Gail and D{\"o}rr, Marcus and Ehret, Georg and Ellis, Stephen B and Feenstra, Bjarke and Feitosa, Mary F and Ford, Ian and Fox, Caroline S and Frayling, Timothy M and Friedrich, Nele and Geller, Frank and Scotland, Generation and Gillham-Nasenya, Irina and Gottesman, Omri and Graff, Misa and Grodstein, Francine and Gu, Charles and Haley, Chris and Hammond, Christopher J and Harris, Sarah E and Harris, Tamara B and Hastie, Nicholas D and Heard-Costa, Nancy L and Heikkil{\"a}, Kauko and Hocking, Lynne J and Homuth, Georg and Hottenga, Jouke-Jan and Huang, Jinyan and Huffman, Jennifer E and Hysi, Pirro G and Ikram, M Arfan and Ingelsson, Erik and Joensuu, Anni and Johansson, {\r A}sa and Jousilahti, Pekka and Jukema, J Wouter and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kanoni, Stavroula and Kerr, Shona M and Khan, Nazir M and Koellinger, Philipp and Koistinen, Heikki A and Kooner, Manraj K and Kubo, Michiaki and Kuusisto, Johanna and Lahti, Jari and Launer, Lenore J and Lea, Rodney A and Lehne, Benjamin and Lehtim{\"a}ki, Terho and Liewald, David C M and Lind, Lars and Loh, Marie and Lokki, Marja-Liisa and London, Stephanie J and Loomis, Stephanie J and Loukola, Anu and Lu, Yingchang and Lumley, Thomas and Lundqvist, Annamari and M{\"a}nnist{\"o}, Satu and Marques-Vidal, Pedro and Masciullo, Corrado and Matchan, Angela and Mathias, Rasika A and Matsuda, Koichi and Meigs, James B and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Mentch, Frank D and Mihailov, Evelin and Milani, Lili and Montasser, May E and Montgomery, Grant W and Morrison, Alanna and Myers, Richard H and Nadukuru, Rajiv and Navarro, Pau and Nelis, Mari and Nieminen, Markku S and Nolte, Ilja M and O{\textquoteright}Connor, George T and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmas, Walter R and Pankow, James S and Patarcic, Inga and Pavani, Francesca and Peyser, Patricia A and Pietilainen, Kirsi and Poulter, Neil and Prokopenko, Inga and Ralhan, Sarju and Redmond, Paul and Rich, Stephen S and Rissanen, Harri and Robino, Antonietta and Rose, Lynda M and Rose, Richard and Sala, Cinzia and Salako, Babatunde and Salomaa, Veikko and Sarin, Antti-Pekka and Saxena, Richa and Schmidt, Helena and Scott, Laura J and Scott, William R and Sennblad, Bengt and Seshadri, Sudha and Sever, Peter and Shrestha, Smeeta and Smith, Blair H and Smith, Jennifer A and Soranzo, Nicole and Sotoodehnia, Nona and Southam, Lorraine and Stanton, Alice V and Stathopoulou, Maria G and Strauch, Konstantin and Strawbridge, Rona J and Suderman, Matthew J and Tandon, Nikhil and Tang, Sian-Tsun and Taylor, Kent D and Tayo, Bamidele O and T{\"o}glhofer, Anna Maria and Tomaszewski, Maciej and T{\v s}ernikova, Natalia and Tuomilehto, Jaakko and Uitterlinden, Andre G and Vaidya, Dhananjay and van Hylckama Vlieg, Astrid and van Setten, Jessica and Vasankari, Tuula and Vedantam, Sailaja and Vlachopoulou, Efthymia and Vozzi, Diego and Vuoksimaa, Eero and Waldenberger, Melanie and Ware, Erin B and Wentworth-Shields, William and Whitfield, John B and Wild, Sarah and Willemsen, Gonneke and Yajnik, Chittaranjan S and Yao, Jie and Zaza, Gianluigi and Zhu, Xiaofeng and BioBank Japan Project and Salem, Rany M and Melbye, Mads and Bisgaard, Hans and Samani, Nilesh J and Cusi, Daniele and Mackey, David A and Cooper, Richard S and Froguel, Philippe and Pasterkamp, Gerard and Grant, Struan F A and Hakonarson, Hakon and Ferrucci, Luigi and Scott, Robert A and Morris, Andrew D and Palmer, Colin N A and Dedoussis, George and Deloukas, Panos and Bertram, Lars and Lindenberger, Ulman and Berndt, Sonja I and Lindgren, Cecilia M and Timpson, Nicholas J and T{\"o}njes, Anke and Munroe, Patricia B and S{\o}rensen, Thorkild I A and Rotimi, Charles N and Arnett, Donna K and Oldehinkel, Albertine J and Kardia, Sharon L R and Balkau, Beverley and Gambaro, Giovanni and Morris, Andrew P and Eriksson, Johan G and Wright, Margie J and Martin, Nicholas G and Hunt, Steven C and Starr, John M and Deary, Ian J and Griffiths, Lyn R and Tiemeier, Henning and Pirastu, Nicola and Kaprio, Jaakko and Wareham, Nicholas J and P{\'e}russe, Louis and Wilson, James G and Girotto, Giorgia and Caulfield, Mark J and Raitakari, Olli and Boomsma, Dorret I and Gieger, Christian and van der Harst, Pim and Hicks, Andrew A and Kraft, Peter and Sinisalo, Juha and Knekt, Paul and Johannesson, Magnus and Magnusson, Patrik K E and Hamsten, Anders and Schmidt, Reinhold and Borecki, Ingrid B and Vartiainen, Erkki and Becker, Diane M and Bharadwaj, Dwaipayan and Mohlke, Karen L and Boehnke, Michael and van Duijn, Cornelia M and Sanghera, Dharambir K and Teumer, Alexander and Zeggini, Eleftheria and Metspalu, Andres and Gasparini, Paolo and Ulivi, Sheila and Ober, Carole and Toniolo, Daniela and Rudan, Igor and Porteous, David J and Ciullo, Marina and Spector, Tim D and Hayward, Caroline and Dupuis, Jos{\'e}e and Loos, Ruth J F and Wright, Alan F and Chandak, Giriraj R and Vollenweider, Peter and Shuldiner, Alan R and Ridker, Paul M and Rotter, Jerome I and Sattar, Naveed and Gyllensten, Ulf and North, Kari E and Pirastu, Mario and Psaty, Bruce M and Weir, David R and Laakso, Markku and Gudnason, Vilmundur and Takahashi, Atsushi and Chambers, John C and Kooner, Jaspal S and Strachan, David P and Campbell, Harry and Hirschhorn, Joel N and Perola, Markus and Pola{\v s}ek, Ozren and Wilson, James F}
}
@article {836891,
	title = {Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies.},
	journal = {Gastroenterology},
	volume = {151},
	number = {2},
	year = {2016},
	month = {2016 Aug},
	pages = {351-363.e28},
	abstract = {BACKGROUND \&amp; AIMS: A genome-wide association study (GWAS) of 280 cases identified the hepatic cholesterol transporter ABCG8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other GWAS of this phenotype. We performed a large-scale, meta-analysis of GWASs of individuals of European ancestry with available prior genotype data, to identify additional genetic risk factors for gallstone disease. METHODS: We obtained per-allele odds ratio (OR) and standard error estimates using age- and sex-adjusted logistic regression models within each of the 10 discovery studies (8720 cases and 55,152 controls). We performed an inverse variance weighted, fixed-effects meta-analysis of study-specific estimates to identify single-nucleotide polymorphisms that were associated independently with gallstone disease. Associations were replicated in 6489 cases and 62,797 controls. RESULTS: We observed independent associations for 2 single-nucleotide polymorphisms at the ABCG8 locus: rs11887534 (OR, 1.69; 95\% confidence interval [CI], 1.54-1.86; P\&nbsp;= 2.44\&nbsp;{\texttimes} 10(-60)) and rs4245791 (OR, 1.27; P\&nbsp;= 1.90\&nbsp;{\texttimes} 10(-34)). We also identified and/or replicated associations for rs9843304 in TM4SF4 (OR, 1.12; 95\% CI, 1.08-1.16; P\&nbsp;= 6.09\&nbsp;{\texttimes} 10(-11)), rs2547231 in SULT2A1 (encodes a sulfoconjugation enzyme that acts on hydroxysteroids and cholesterol-derived sterol bile acids) (OR, 1.17; 95\% CI, 1.12-1.21; P\&nbsp;= 2.24\&nbsp;{\texttimes} 10(-10)), rs1260326 in glucokinase regulatory protein (OR, 1.12; 95\% CI, 1.07-1.17; P\&nbsp;=\&nbsp;2.55\&nbsp;{\texttimes} 10(-10)), and rs6471717 near CYP7A1 (encodes an enzyme that catalyzes conversion of cholesterol to primary bile acids) (OR, 1.11; 95\% CI, 1.08-1.15; P\&nbsp;= 8.84\&nbsp;{\texttimes} 10(-9)). Among individuals of African American and Hispanic American ancestry, rs11887534 and rs4245791 were associated positively with gallstone disease risk, whereas the\&nbsp;association for the rs1260326 variant was inverse. CONCLUSIONS: In this large-scale GWAS of gallstone disease, we identified 4 loci in genes that have putative functions in cholesterol metabolism and transport, and sulfonylation of bile acids or hydroxysteroids.},
	issn = {1528-0012},
	doi = {10.1053/j.gastro.2016.04.007},
	author = {Joshi, Amit D and Andersson, Charlotte and Buch, Stephan and Stender, Stefan and Noordam, Raymond and Weng, Lu-Chen and Weeke, Peter E and Auer, Paul L and Boehm, Bernhard and Chen, Constance and Choi, Hyon and Curhan, Gary and Denny, Joshua C and De Vivo, Immaculata and Eicher, John D and Ellinghaus, David and Folsom, Aaron R and Fuchs, Charles and Gala, Manish and Haessler, Jeffrey and Hofman, Albert and Hu, Frank and Hunter, David J and Janssen, Harry L A and Kang, Jae H and Kooperberg, Charles and Kraft, Peter and Kratzer, Wolfgang and Lieb, Wolfgang and Lutsey, Pamela L and Darwish Murad, Sarwa and Nordestgaard, B{\o}rge G and Pasquale, Louis R and Reiner, Alex P and Ridker, Paul M and Rimm, Eric and Rose, Lynda M and Shaffer, Christian M and Schafmayer, Clemens and Tamimi, Rulla M and Uitterlinden, Andr{\'e} G and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Wakabayashi, Yoshiyuki and Wiggs, Janey L and Zhu, Jun and Roden, Dan M and Stricker, Bruno H and Tang, Weihong and Teumer, Alexander and Hampe, Jochen and Tybj{\ae}rg-Hansen, Anne and Chasman, Daniel I and Chan, Andrew T and Johnson, Andrew D}
}
@article {1474202,
	title = {Acellular nerve allografts in corneal neurotisation: an inappropriate choice},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {149-150},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-315032},
	author = {Nate Jowett and Pineda Ii, Roberto}
}
@article {1608594,
	title = {Corneal and Facial Sensory Neurotization in Trigeminal Anesthesia},
	journal = {Facial Plast Surg Clin North Am},
	volume = {29},
	number = {3},
	year = {2021},
	month = {2021 Aug},
	pages = {459-470},
	abstract = {Trigeminal anesthesia may yield blindness and facial disfigurement, secondary to neurotrophic keratopathy and trigeminal trophic syndrome. This article summarizes contemporary medical and emerging surgical approaches for the therapeutic management of this rare and devastating disease state.},
	issn = {1558-1926},
	doi = {10.1016/j.fsc.2021.03.011},
	author = {Nate Jowett and Pineda, Roberto}
}
@article {1608601,
	title = {Seeing through the evidence for corneal neurotization},
	journal = {Curr Opin Otolaryngol Head Neck Surg},
	volume = {29},
	number = {4},
	year = {2021},
	month = {2021 Aug 01},
	pages = {252-258},
	abstract = {PURPOSE OF REVIEW: Trigeminal anesthesia causes neurotrophic keratopathy, which may yield facial disfigurement and corneal blindness. RECENT FINDINGS: We summarize approaches and evidence for corneal neurotization. SUMMARY: Regional sensory nerve transfer appears safe and effective for therapeutic management of neurotrophic keratopathy. Prospective randomized clinical trials are necessary to confirm the utility of corneal neurotization.},
	issn = {1531-6998},
	doi = {10.1097/MOO.0000000000000731},
	author = {Nate Jowett and Pineda, Roberto}
}
@article {669236,
	title = {Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1.},
	journal = {Nat Med},
	volume = {22},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {439-45},
	abstract = {Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine. Current dogma suggests that high-energy-consuming photoreceptors depend on glucose. Here we show that the retina also uses fatty acid β-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid. In the retinas of Vldlr(-/-) mice with low fatty acid uptake but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate α-ketoglutarate (α-KG). Low α-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlr(-/-) photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlr(-/-) retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD), which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases.},
	issn = {1546-170X},
	doi = {10.1038/nm.4059},
	author = {Joyal, Jean-S{\'e}bastien and Sun, Ye and Gantner, Marin L and Shao, Zhuo and Evans, Lucy P and Saba, Nicholas and Fredrick, Thomas and Burnim, Samuel and Kim, Jin Sung and Patel, Gauri and Juan, Aimee M and Hurst, Christian G and Hatton, Colman J and Cui, Zhenghao and Pierce, Kerry A and Bherer, Patrick and Aguilar, Edith and Powner, Michael B and Vevis, Kristis and Boisvert, Michel and Fu, Zhongjie and Levy, Emile and Fruttiger, Marcus and Packard, Alan and Rezende, Flavio A and Maranda, Bruno and Sapieha, Przemyslaw and Chen, Jing and Friedlander, Martin and Clish, Clary B and Smith, Lois E H}
}
@article {1263351,
	title = {Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism},
	journal = {Prog Retin Eye Res},
	volume = {64},
	year = {2018},
	month = {2018 May},
	pages = {131-156},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2017.11.002},
	author = {Joyal, Jean-S{\'e}bastien and Gantner, Marin L and Smith, Lois E H}
}
@article {1364620,
	title = {Proliferative capacity of corneal endothelial cells},
	journal = {Exp Eye Res},
	volume = {95},
	number = {1},
	year = {2012},
	month = {2012 Feb},
	pages = {16-23},
	abstract = {The corneal endothelial monolayer helps maintain corneal transparency through its barrier and ionic "pump" functions. This transparency function can become compromised, resulting in a critical loss in endothelial cell density (ECD), corneal edema, bullous keratopathy, and loss of visual acuity. Although penetrating keratoplasty and various forms of endothelial keratoplasty are capable of restoring corneal clarity, they can also have complications requiring re-grafting or other treatments. With the increasing worldwide shortage of donor corneas to be used for keratoplasty, there is a greater need to find new therapies to restore corneal clarity that is lost due to endothelial dysfunction. As a result, researchers have been exploring alternative approaches that could result in the in\&nbsp;vivo induction of transient corneal endothelial cell division or the in\&nbsp;vitro expansion of healthy endothelial cells for corneal bioengineering as treatments to increase ECD and restore visual acuity. This review presents current information regarding the ability of human corneal endothelial cells (HCEC) to divide as a basis for the development of new therapies. Information will be presented on the positive and negative regulation of the cell cycle as background for the studies to be discussed. Results of studies exploring the proliferative capacity of HCEC will be presented and specific conditions that affect the ability of HCEC to divide will be discussed. Methods that have been tested to induce transient proliferation of HCEC will also be presented. This review will discuss the effect of donor age and endothelial topography on relative proliferative capacity of HCEC, as well as explore the role of nuclear oxidative DNA damage in decreasing the relative proliferative capacity of HCEC. Finally, potential new research directions will be discussed that could take advantage of and/or improve the proliferative capacity of these physiologically important cells in order to develop new treatments to restore corneal clarity.},
	keywords = {Age Factors, Animals, Cell Cycle Checkpoints, Cell Proliferation, Cornea, Corneal Diseases, Corneal Transplantation, DNA Damage, Donor Selection, Endothelial Cells, Humans, Oxidative Stress, Tissue Engineering},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2011.08.014},
	author = {Joyce, Nancy C}
}
@article {1623366,
	title = {Impact of perioperative dexmedetomidine use in cataract surgery},
	journal = {J Cataract Refract Surg},
	volume = {48},
	number = {7},
	year = {2022},
	month = {2022 07 01},
	pages = {855-857},
	keywords = {Cataract, Cataract Extraction, Dexmedetomidine, Humans, Perioperative Care},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000000870},
	author = {Juang, Jeremy and Xiao, Mark and Chen, Sherleen Huang and Macias, Alvaro Andres}
}
@article {1490456,
	title = {Advances and limitations of drug delivery systems formulated as eye drops},
	journal = {J Control Release},
	volume = {321},
	year = {2020},
	month = {2020 May 10},
	pages = {1-22},
	abstract = {Topical instillation of eye drops remains the most common and easiest route of ocular drug administration, representing the treatment of choice for many ocular diseases. Nevertheless, low ocular bioavailability of topically applied drug molecules can considerably limit their efficacy. Over the last several decades, numerous drug delivery systems (DDS) have been developed in order to improve drug bioavailability on the ocular surfaces. This review systematically covers the most recent advances of DDS applicable by topical instillation, that have shown better performance in in vivo models compared to standard eye drop formulations. These delivery systems are based on in situ forming gels, nanoparticles and combinations of both. Most of the DDS have been developed using natural or synthetic polymers. Polymers offer many advantageous properties for designing advanced DDS including biocompatibility, gelation properties and/or mucoadhesiveness. However, despite the high number of studies published over the last decade, there are several limitations for clinical translation of DDS. This review article focuses on the recent advances for the development of ocular drug delivery systems. In addtion, the potential challenges for commercialization of new DDS are presented.},
	issn = {1873-4995},
	doi = {10.1016/j.jconrel.2020.01.057},
	author = {Jumelle, Clotilde and Gholizadeh, Shima and Annabi, Nasim and Dana, Reza}
}
@article {1619426,
	title = {Development and characterization of a hydrogel-based adhesive patch for sealing open-globe injuries},
	journal = {Acta Biomater},
	volume = {137},
	year = {2022},
	month = {2022 01 01},
	pages = {53-63},
	abstract = {Full-thickness wounds to the eye can lead to serious vision impairment. Current standards of care (from suturing to tissue transplantation) usually require highly skilled surgeons and use of an operating theater. In this study, we report the synthesis, optimization, and in vitro and ex vivo testing of photocrosslinkable hydrogel-based adhesive patches that can easily be applied to globe injuries or corneal incisions. According to the type and concentration of polymers used in the adhesive formulations, we were able to finely tune the physical properties of the bioadhesive including viscosity, elastic modulus, extensibility, ultimate tensile strength, adhesion, transparency, water content, degradation time, and swellability. Our in vitro studies showed no sign of cytotoxicity of the hydrogels. Moreover, the hydrogel patches showed higher adhesion on freshly explanted pig eyeballs compared to a marketed ocular sealant. Finally, ex vivo feasibility studies showed that the hydrogel patches could seal complex open-globe injuries such as large incision, cruciform injury, and injury associated with tissue loss. These results suggest that our photocrosslinkable hydrogel patch could represent a promising solution for the sealing of open-globe injuries or surgical incisions. STATEMENT OF SIGNIFICANCE: Current management of severe ocular injuries require advanced surgical skills and access to an operating theater. To address the need for emergent management of wounds that cannot be handled in the operating room, surgical adhesives have gained popularity, but none of the currently available adhesives have optimal bioavailability, adhesive or mechanical properties. This study describes the development, optimization and testing of a light-sensitive adhesive patch that can easily be applied to the eye. After solidification using visible light, the patch shows no toxicity and is more adherent to the tissue than a marketed sealant. Thus this technology could represent a promising solution to stabilize ocular injuries in emergency settings before definitive surgical repair.},
	keywords = {Adhesives, Animals, Cornea, Hydrogels, Swine, Tensile Strength, Tissue Adhesives},
	issn = {1878-7568},
	doi = {10.1016/j.actbio.2021.10.021},
	author = {Jumelle, Clotilde and Yung, Ann and Shirzaei Sani, Ehsan and Taketani, Yukako and Gantin, Fanny and Bourel, Louisa and Wang, Shudan and Y{\"u}ksel, Erdem and Seneca, Senne and Annabi, Nasim and Dana, Reza}
}
@article {630291,
	title = {A novel Alzheimer disease locus located near the gene encoding tau protein.},
	journal = {Mol Psychiatry},
	volume = {21},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {108-117},
	abstract = {APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer{\textquoteright}s Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P\&lt;1 {\texttimes} 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5{\textperiodcentered}8 {\texttimes} 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1{\textperiodcentered}6 {\texttimes} 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P⩽1.3 {\texttimes} 10(-8)), frontal cortex (P⩽1.3 {\texttimes} 10(-9)) and temporal cortex (P⩽1.2 {\texttimes} 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 {\texttimes} 10(-6)) and temporal cortex (P=2.6 {\texttimes} 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.},
	issn = {1476-5578},
	doi = {10.1038/mp.2015.23},
	author = {Jun, G and Ibrahim-Verbaas, C A and Vronskaya, M and Lambert, J-C and Chung, J and Naj, A C and Kunkle, B W and Wang, L-S and Bis, J C and Bellenguez, C and Harold, D and Lunetta, K L and Destefano, A L and Grenier-Boley, B and Sims, R and Beecham, G W and Smith, A V and Chouraki, V and Hamilton-Nelson, K L and Ikram, M A and Fievet, N and Denning, N and Martin, E R and Schmidt, H and Kamatani, Y and Dunstan, M L and Valladares, O and Laza, A R and Zelenika, D and Ramirez, A and Foroud, T M and Choi, S-H and Boland, A and Becker, T and Kukull, W A and van der Lee, S J and Pasquier, F and Cruchaga, C and Beekly, D and Fitzpatrick, A L and Hanon, O and Gill, M and Barber, R and Gudnason, V and Campion, D and Love, S and Bennett, D A and Amin, N and Berr, C and Tsolaki, Magda and Buxbaum, J D and Lopez, O L and Deramecourt, V and Fox, N C and Cantwell, L B and T{\'a}rraga, L and Dufouil, C and Hardy, J and Crane, P K and Eiriksdottir, G and Hannequin, D and Clarke, R and Evans, D and Mosley, T H and Letenneur, L and Brayne, C and Maier, W and De Jager, P and Emilsson, V and Dartigues, J-F and Hampel, H and Kamboh, M I and de Bruijn, R F A G and Tzourio, C and Pastor, P and Larson, E B and Rotter, J I and O{\textquoteright}Donovan, M C and Montine, T J and Nalls, M A and Mead, S and Reiman, E M and Jonsson, P V and Holmes, C and St George-Hyslop, P H and Boada, M and Passmore, P and Wendland, J R and Schmidt, R and Morgan, K and Winslow, A R and Powell, J F and Carasquillo, M and Younkin, S G and Jakobsd{\'o}ttir, J and Kauwe, J S K and Wilhelmsen, K C and Rujescu, D and N{\"o}then, M M and Hofman, A and Jones, L and IGAP Consortium and Haines, J L and Psaty, B M and Van Broeckhoven, C and Holmans, P and Launer, L J and Mayeux, R and Lathrop, M and Goate, A M and Escott-Price, V and Seshadri, S. and Pericak-Vance, M A and Amouyel, P and Williams, J and van Duijn, C M and Schellenberg, G D and Farrer, L A}
}
@article {1619420,
	title = {Photographic Depiction of the Field of View with Spectacles-mounted Low Vision Aids},
	journal = {Optom Vis Sci},
	volume = {98},
	number = {10},
	year = {2021},
	month = {2021 Oct 01},
	pages = {1210-1226},
	abstract = {SIGNIFICANCE: Photographic depiction helps to illustrate the primary and secondary field of view effects of low vision devices along with their utility to clinicians, patients, and caretakers. This technique may also be helpful for designers and researchers in improving the design and fitting of low vision devices. PURPOSE: The field of view through spectacles-mounted low vision devices has typically been evaluated using perimetry. However, the perimetric field diagram is different from the retinal image and often fails to represent the important aspects of the field of view and visual parameters. We developed a photographic depiction method to record and veridically show the field of view effects of these devices. METHODS: We used a 3D-printed holder to place spectacles-mounted devices at the same distance from the empirically determined reference point of the field of view in a camera lens (f = 16 mm) as they would be from an eye, when in use. The field of view effects of a bioptic telescope, a minifier (reverse telescope), and peripheral prisms were captured using a conventional camera, representing retinal images. The human eye pupil size (adjusting the F number: f/2.8 to f/8 and f/22 in the camera lens) and fitting parameters (pantoscopic tilt and back vertex distance) varied. RESULTS: Real-world indoor and outdoor walking and driving scenarios were depicted as retinal images illustrating the field of view through low vision devices, distinguishing optical and obscuration scotomas, and demonstrating secondary effects (spatial distortions, viewpoint changes, diplopia, spurious reflection, and multiplexing effects) not illustrated by perimetric field diagrams. CONCLUSIONS: Photographic depiction illustrates the primary and secondary field of view effects of the low vision devices. These images highlight the benefit and possible trade-offs of the low vision devices and may be beneficial in education and training.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001790},
	author = {Jung, Jae-Hyun and Kurukuti, Nish Mohith and Peli, Eli}
}
@article {1328890,
	title = {Field Expansion for Acquired Monocular Vision Using a Multiplexing Prism},
	journal = {Optom Vis Sci},
	volume = {95},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {814-828},
	abstract = {SIGNIFICANCE: Acquired monocular vision (AMV) is a common visual field loss. Patients report mobility difficulties in walking due to collisions with objects or other pedestrians on the blind side. PURPOSE: The visual field of people with AMV extends more than 90{\textdegree} temporally on the side of the seeing eye but is restricted to approximately 55{\textdegree} nasally. We developed a novel field expansion device using a multiplexing prism (MxP) that superimposes the see-through and shifted views for true field expansion without apical scotoma. We present various designs of the device that enable customized fitting and improved cosmetics. METHODS: A partial MxP segment is attached (base-in) near the nose bridge. To avoid total internal reflection due to the high angle of incidence at nasal field end (55{\textdegree}), we fit the MxP with serrations facing the eye and tilt the prism base toward the nose. We calculated the width of the MxP (the apex location) needed to prevent apical scotoma and monocular diplopia. We also consider the effect of spectacle prescriptions on these settings. The results are verified perimetrically. RESULTS: We documented the effectivity of various prototype glasses designs with perimetric measurements. With the prototypes, all patients with AMV had field-of-view expansions up to 90{\textdegree} nasally without any loss of seeing field. CONCLUSIONS: The novel and properly mounted MxP in glasses has the potential for meaningful field-of-view expansion up to the size of normal binocular vision in cosmetically acceptable form.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001277},
	author = {Jung, Jae-Hyun and Peli, Eli}
}
@article {1328891,
	title = {No Useful Field Expansion with Full-field Prisms},
	journal = {Optom Vis Sci},
	volume = {95},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {805-813},
	abstract = {SIGNIFICANCE: Full-field prisms that fill the entire spectacle eye wire have been considered as field expansion devices for homonymous hemianopia (HH) and acquired monocular vision (AMV). Although the full-field prism is used for addressing binocular dysfunction and for prism adaptation training after brain injury as treatment for spatial hemineglect, we show that the full-field prism for field expansion does not effectively expand the visual field in either HH or AMV. PURPOSE: Full-field prisms may shift a portion of the blind side to the residual seeing side. However, foveal fixation on an object of interest through a full-field prism requires head and/or eye rotation away from the blind side, thus negating the shift of the field toward the blind side. METHODS: We fit meniscus and flat full-field 7Δ and 12Δ yoked prisms and conducted Goldmann perimetry in HH and AMV. We compared the perimetry results with ray tracing calculations. RESULTS: The rated prism power was in effect at the primary position of gaze for all prisms, and the meniscus prisms maintained almost constant power at all eccentricities. To fixate on the perimetry target, the subjects needed to turn their head and/or eyes away from the blind side, which negated the field shift into the blind side. In HH, there was no difference in the perimetry results on the blind side with any of the prisms. In AMV, the lower nasal field of view was slightly shifted into the blind side with the flat prisms, but not with the meniscus prisms. CONCLUSIONS: Full-field prisms are not an effective field expansion device owing to the inevitable fixation shift. There is potential for a small field shift with the flat full-field prism in AMV, but such lenses cannot incorporate refractive correction. Furthermore, in considering the apical scotoma, the shift provides a mere field substitution at best.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001271},
	author = {Jung, Jae-Hyun and Peli, Eli}
}
@article {1354355,
	title = {Impact of high power and angle of incidence on prism corrections for visual field loss},
	journal = {Opt Eng},
	volume = {53},
	number = {6},
	year = {2014},
	month = {2014 Jan 17},
	abstract = {Prism distortions and spurious reflections are not usually considered when prescribing prisms to compensate for visual field loss due to homonymous hemianopia. Distortions and reflections in the high power Fresnel prisms used in peripheral prism placement can be considerable, and the simplifying assumption that prism deflection power is independent of angle of incidence into the prisms results in substantial errors. We analyze the effects of high prism power and incidence angle on the field expansion, size of the apical scotomas, and image compression/expansion. We analyze and illustrate the effects of reflections within the Fresnel prisms, primarily due to reflections at the bases, and secondarily due to surface reflections. The strength and location of these effects differs materially depending on whether the serrated prismatic surface is placed toward or away from the eye, and this affects the contribution of the reflections to visual confusion, diplopia, false alarms, and loss of contrast. We conclude with suggestions for controlling and mitigating these effects in clinical practice.},
	issn = {0091-3286},
	doi = {10.1117/1.OE.53.6.061707},
	author = {Jung, Jae-Hyun and Peli, Eli}
}
@article {1125331,
	title = {Disinfection of Tonometers: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {124},
	number = {12},
	year = {2017},
	month = {2017 Dec},
	pages = {1867-1875},
	abstract = {OBJECTIVE: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm. METHODS: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded. RESULTS: The searches initially yielded 64 unique citations. After exclusion criteria were applied, 10 laboratory studies remained for this review. Nine of the 10 studies used tonometer prisms and 1 used steel discs. The infectious agents covered in this assessment include adenovirus 8 and 19, herpes simplex virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus, enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of adenovirus 8 concluded that after sodium hypochlorite (dilute bleach) disinfection, the virus was undetectable, but only 2 of the 4 studies found that 70\% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus. All 3 HSV studies concluded that both sodium hypochlorite and 70\% isopropyl alcohol eliminated HSV. Ethanol, 70\% isopropyl alcohol, dilute bleach, and mechanical cleaning all lack the ability to remove cellular debris completely, which is necessary to prevent prion transmission. Therefore, single-use tonometer tips or disposable tonometer covers should be considered when treating patients with suspected prion disease. Damage to tonometer prisms can be caused by sodium hypochlorite, 70\% isopropyl alcohol, 3\% hydrogen peroxide, ethyl alcohol, water immersion, ultraviolet light, and heat exposure. Disinfectants can cause tonometer tips to swell and crack by dissolving the glue that holds the hollow tip together. The tonometer tip cracks can irritate the cornea, harbor microbes, or allow disinfectants to enter the interior of the tonometer tip. CONCLUSIONS: Sodium hypochlorite (dilute bleach) offers effective disinfection against adenovirus and HSV, the viruses commonly associated with nosocomial outbreaks in eye care. Tonometer prisms should be examined regularly for signs of damage.},
	keywords = {Academies and Institutes, Anti-Infective Agents, Cross Infection, Disinfectants, Disinfection, Humans, Ophthalmology, Technology Assessment, Biomedical, Tonometry, Ocular, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.05.033},
	author = {Junk, Anna K and Chen, Philip P and Lin, Shan C and Nouri-Mahdavi, Kouros and Radhakrishnan, Sunita and Singh, Kuldev and Chen, Teresa C}
}
@article {1511489,
	title = {Current Trends in Tonometry and Tonometer Tip Disinfection},
	journal = {J Glaucoma},
	volume = {29},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {507-512},
	abstract = {PRECIS: A survey among members of the American Glaucoma Society (AGS) and the American Optometry Association (AOA) on tonometer preference and tonometer disinfection indicates a shift to disposable tonometer tips compared with 1987. PURPOSE: This survey{\textquoteright}s purpose was to determine how eye care providers responded to the 2008 Centers of Disease Control (CDC) tonometer disinfection guidelines, which recommend 10\% hypochlorite (dilute bleach) for reusable tonometers. Tonometers measure the eye pressure when they touch the cornea, an essential part of the eye examination. METHODS: AGS and AOA members were surveyed on tonometer preference, tonometer use, disinfection process, disinfectants, disinfection timing, and tonometer damage. RESULTS: Survey responses from 79 AOA members and 197 AGS members are included. The Goldmann tonometer is considered most accurate (70, 89\% AOA and 161, 82\% AGS). It is preferred by 54 (70\%) AOA and 193 (98\%) AGS members. Many providers (165) use reusable Goldmann tonometer tips (77, 79\% AOA, 88, 45\% AGS), and most clean with 70\% isopropyl alcohol wipes 59 (77\%) AOA and 54 (61\%) AGS. In summary, 126 of 276 participants (8, 10\% AOA and 118, 60\% AGS) follow CDC guidelines by using disposable tips (2 AOA and 109 AGS) or disinfecting reusable tips with 10\% hypochlorite (6 AOA and 9 AGS). CONCLUSIONS: The majority of AGS providers follow current CDC tonometer disinfection guidelines by shifting to disposable Goldmann tonometer tips. Only a minority of providers who use reusable tonometer tips disinfect with dilute bleach. Continued education on proper tonometer disinfection is critical to prevent eye-care related infection due to improper disinfection.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001566},
	author = {Junk, Anna K and Chang, Ta Chen and Vanner, Elizabeth and Chen, Teresa}
}
@article {1586177,
	title = {Novel variants in TUBA1A cause congenital fibrosis of the extraocular muscles with or without malformations of cortical brain development},
	journal = {Eur J Hum Genet},
	volume = {29},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {816-826},
	abstract = {Variants in multiple tubulin genes have been implicated in neurodevelopmental disorders, including malformations of cortical development (MCD) and congenital fibrosis of the extraocular muscles (CFEOM). Distinct missense variants in the beta-tubulin encoding genes TUBB3 and TUBB2B cause MCD, CFEOM, or both, suggesting substitution-specific mechanisms. Variants in the alpha tubulin-encoding gene TUBA1A have been associated with MCD, but not with CFEOM. Using exome sequencing (ES) and genome sequencing (GS), we identified 3 unrelated probands with CFEOM who harbored novel heterozygous TUBA1A missense variants c.1216C\&gt;G, p.(His406Asp); c.467G\&gt;A, p.(Arg156His); and c.1193T\&gt;G, p.(Met398Arg). MRI revealed small oculomotor-innervated muscles and asymmetrical caudate heads and lateral ventricles with or without corpus callosal thinning. Two of the three probands had MCD. Mutated amino acid residues localize either to the longitudinal interface at which α and β tubulins heterodimerize (Met398, His406) or to the lateral interface at which tubulin protofilaments interact (Arg156), and His406 interacts with the motor domain of kinesin-1. This series of individuals supports TUBA1A variants as a cause of CFEOM and expands our knowledge of tubulinopathies.},
	issn = {1476-5438},
	doi = {10.1038/s41431-020-00804-7},
	author = {Jurgens, Julie A and Barry, Brenda J and Lemire, Gabrielle and Chan, Wai-Man and Whitman, Mary C and Shaaban, Sherin and Robson, Caroline D and MacKinnon, Sarah and England, Eleina M and McMillan, Hugh J and Kelly, Christopher and Pratt, Brandon M and Care4Rare Canada Consortium and O{\textquoteright}Donnell-Luria, Anne and MacArthur, Daniel G and Boycott, Kym M and Hunter, David G and Engle, Elizabeth C}
}
@article {1359933,
	title = {Fuchs Endothelial Corneal Dystrophy Through the Prism of Oxidative Stress},
	journal = {Cornea},
	volume = {37 Suppl 1},
	year = {2018},
	month = {2018 Nov},
	pages = {S50-S54},
	abstract = {The corneal endothelium (CE) is vital for maintaining the water balance and clarity of the cornea. The CE is a cell layer that is particularly susceptible to aging because of its postmitotic arrest, high metabolic activity involving pumping of ions, and lifelong exposure to ultraviolet light. Despite gradual age-related cell loss, a sufficient number of CE cells are preserved during the lifespan of an individual. However, in conditions such as Fuchs endothelial corneal dystrophy (FECD), permanent loss of CE cells leads to corneal edema and loss of vision requiring corneal transplantation. FECD is a genetic and oxidative stress disorder manifested by abnormal cell-matrix interactions and expedited cellular aging culminating in cellular death. Because the endothelium has minimal replicative capacity in vivo and an inability to replace its genome, it is particularly prone to cumulative DNA damage acquired throughout life. In FECD, the underlying genetic defects make the CE genome even more vulnerable to this damage, to the point of causing mitochondrial dysfunction, mitochondrial membrane potential loss, and excessive mitophagy activation. Endogenous and exogenous intracellular stressors alter the synthetic footprint of CE cells, leading to endothelial-mesenchymal transition and secretion of aberrant extracellular matrix (in the form of guttae), resembling scar formation in other organs. In turn, the guttae or endothelial scars contribute to a vicious cycle of FECD pathogenesis and, by further inducing endothelial-mesenchymal transition and oxidant-antioxidant imbalance, perpetuate the molecular changes of the degenerating endothelium.},
	keywords = {Antioxidants, DNA Damage, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Mitochondria, Oxidative Stress, Reactive Oxygen Species},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001775},
	author = {Jurkunas, Ula V}
}
@article {1748436,
	title = {Cultivated autologous limbal epithelial cell (CALEC) transplantation: Development of manufacturing process and clinical evaluation of feasibility and safety},
	journal = {Sci Adv},
	volume = {9},
	number = {33},
	year = {2023},
	month = {2023 Aug 18},
	pages = {eadg6470},
	abstract = {To treat unilateral limbal stem cell (LSC) deficiency, we developed cultivated autologous limbal epithelial cells (CALEC) using an innovative xenobiotic-free, serum-free, antibiotic-free, two-step manufacturing process for LSC isolation and expansion onto human amniotic membrane with rigorous quality control in a good manufacturing practices facility. Limbal biopsies were used to generate CALEC constructs, and final grafts were evaluated by noninvasive scanning microscopy and tested for viability and sterility. Cultivated cells maintained epithelial cell phenotype with colony-forming and proliferative capacities. Analysis of LSC biomarkers showed preservation of "stemness." After preclinical development, a phase 1 clinical trial enrolled five patients with unilateral LSC deficiency. Four of these patients received CALEC transplants, establishing preliminary feasibility. Clinical case histories are reported, with no primary safety events. On the basis of these results, a second recruitment phase of the trial was opened to provide longer term safety and efficacy data on more patients.},
	keywords = {Anti-Bacterial Agents, Biopsy, Commerce, Epithelial Cells, Feasibility Studies, Humans, Limbal Stem Cell Deficiency},
	issn = {2375-2548},
	doi = {10.1126/sciadv.adg6470},
	author = {Jurkunas, Ula V and Yin, Jia and Johns, Lynette K and Li, Sanming and Negre, Helene and Shaw, Kit L and Samarakoon, Lassana and Ayala, Allison R and Kheirkhah, Ahmad and Katikireddy, Kishore and Gauthier, Alex and Ong Tone, Stephan and Kaufman, Aaron R and Ellender, Stacey and Hernandez Rodriguez, Diego E and Daley, Heather and Dana, Reza and Armant, Myriam and Ritz, Jerome}
}
@article {1333850,
	title = {Prevalence and causes of vision loss in North Africa and Middle East in 2015: magnitude, temporal trends and projections},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {863-870},
	abstract = {BACKGROUND: To assess the\&nbsp;prevalence and causes of vision impairment in North Africa and the Middle East (NAME) from 1990 to 2015 and to forecast projections for 2020. METHODS: Based on a systematic review of medical literature, the\&nbsp;prevalence of blindness (presenting visual acuity (PVA)\&nbsp;\&lt;3/60 in the better eye), moderate and severe vision impairment (MSVI; PVA\&nbsp;\&lt;6/18 but\&nbsp;>=3/60) and mild vision impairment (PVA\&nbsp;\&lt;6/12 but\&nbsp;>=6/18) was estimated for 2015 and 2020. RESULTS: The age-standardised prevalence of blindness and MSVI for all ages and genders decreased from 1990 to 2015, from 1.72 (0.53-3.13) to 0.95\% (0.32\%-1.71\%), and from 6.66 (3.09-10.69) to 4.62\% (2.21\%-7.33\%), respectively, with slightly higher figures for women than men. Cataract was the most common cause of blindness in 1990 and 2015, followed by uncorrected refractive error. Uncorrected refractive error was the leading cause of MSVI in the NAME region in 1990 and 2015, followed by cataract. A reduction in the proportions of blindness and MSVI due to cataract, corneal opacity and trachoma is predicted by 2020. Conversely, an increase in the proportion of blindness attributable to uncorrected refractive error, glaucoma, age-related macular degeneration and diabetic retinopathy is expected. CONCLUSIONS: In 2015 cataract and uncorrected refractive error were the major causes of vision loss in the NAME region. Proportions of vision impairment from cataract, corneal opacity and trachoma are expected to decrease by 2020, and those from uncorrected refractive error, glaucoma, diabetic retinopathy and age-related macular degeneration are predicted to increase by 2020.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-312068},
	author = {Kahloun, Rim and Khairallah, Moncef and Resnikoff, Serge and Cicinelli, Maria Vittoria and Flaxman, Seth R and Das, Aditi and Jonas, Jost B and Keeffe, Jill E and Kempen, John H and Leasher, Janet and Limburg, Hans and Naidoo, Kovin and Pesudovs, Konrad and Silvester, Alexander J and Tahhan, Nina and Taylor, Hugh R and Wong, Tien Yin and Bourne, Rupert R A and Vision Loss Expert Group of the Global Burden of Disease Study}
}
@article {1603838,
	title = {MyelTracer: A Semi-Automated Software for Myelin -Ratio Quantification},
	journal = {eNeuro},
	volume = {8},
	number = {4},
	year = {2021},
	month = {2021 Jul-Aug},
	abstract = {In the central and peripheral nervous systems, the myelin sheath promotes neuronal signal transduction. The thickness of the myelin sheath changes during development and in disease conditions like multiple sclerosis. Such changes are routinely detected using electron microscopy through g-ratio quantification. While g-ratio is one of the most critical measurements in myelin studies, a major drawback is that g-ratio quantification is extremely laborious and time-consuming. Here, we report the development and validation of MyelTracer, an installable, stand-alone software for semi-automated g-ratio quantification based on the Open Computer Vision Library (OpenCV). Compared with manual g-ratio quantification, using MyelTracer produces consistent results across multiple tissues and animal ages, as well as in remyelination after optic nerve crush, and reduces total quantification time by 40-60\%. With g-ratio measurements via MyelTracer, a known hypomyelination phenotype can be detected in a Williams syndrome mouse model. MyelTracer is easy to use and freely available for Windows and Mac OS X (https://github.com/HarrisonAllen/MyelTracer).},
	issn = {2373-2822},
	doi = {10.1523/ENEURO.0558-20.2021},
	author = {Kaiser, Tobias and Allen, Harrison Mitchell and Kwon, Ohyoon and Barak, Boaz and Wang, Jing and He, Zhigang and Jiang, Minqing and Feng, Guoping}
}
@article {1490462,
	title = {Investigating cone photoreceptor development using patient-derived NRL null retinal organoids},
	journal = {Commun Biol},
	volume = {3},
	number = {1},
	year = {2020},
	month = {2020 Feb 21},
	pages = {82},
	abstract = {Photoreceptor loss is a leading cause of blindness, but mechanisms underlying photoreceptor degeneration are not well understood. Treatment strategies would benefit from improved understanding of gene-expression patterns directing photoreceptor development, as many genes are implicated in both development and degeneration. Neural retina leucine zipper (NRL) is critical for rod photoreceptor genesis and degeneration, with NRL mutations known to cause enhanced S-cone syndrome and retinitis pigmentosa. While murine Nrl loss has been characterized, studies of human NRL can identify important insights for human retinal development and disease. We utilized iPSC organoid models of retinal development to molecularly define developmental alterations in a human model of NRL loss. Consistent with the function of NRL in rod fate specification, human retinal organoids lacking NRL develop S-opsin dominant photoreceptor populations. We report generation of two distinct S-opsin expressing populations in NRL null retinal organoids and identify MEF2C as a candidate regulator of cone development.},
	issn = {2399-3642},
	doi = {10.1038/s42003-020-0808-5},
	author = {Kallman, Alyssa and Capowski, Elizabeth E and Wang, Jie and Kaushik, Aniruddha M and Jansen, Alex D and Edwards, Kimberly L and Chen, Liben and Berlinicke, Cynthia A and Joseph Phillips, M and Pierce, Eric A and Qian, Jiang and Wang, Tza-Huei and Gamm, David M and Zack, Donald J}
}
@article {1538313,
	title = {A pilot study for smartphone photography to assess bleb morphology and vasculature post-trabeculectomy},
	journal = {Int Ophthalmol},
	volume = {41},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {483-490},
	abstract = {PURPOSE: The current grading systems used for bleb morphology assessment in patients post-trabeculectomy are based on standardized slit-lamp photographs and anterior segment imaging devices. The lack of availability of these expensive and non-portable devices in resource-deficient settings is a significant deterrent in their widespread utilization for proper post-operative management. The rapidly evolving utilization of smartphone photography has significantly benefited diagnostics of posterior segment disorders and is now being increasingly utilized for monitoring anterior segment pathologies as well as post-surgical course. In this study, we study a novel use of smartphones for bleb photography for assessing the morphological characteristics as vascularity and microcysts. METHODS: In this pilot, observational study, we compared the trabeculectomy bleb images of five subjects, obtained by iPhone X (dual lens) and iPhone 6S (single lens). We captured two image sets with both smartphones first with a focussed torchlight and then with a built-in flash video light. RESULTS: The images resulting from the newer iPhone X were substantially superior than those from iPhone 6S. For the 12-megapixel dual-camera set-up on the iPhone X, the 1 {\texttimes} lens resulted in better images than the 2 {\texttimes} lens with contrast and overall clarity of the area of interest. While the macro-lens attachment had promising results at 1 {\texttimes} zoom, there is no added advantage of the macro-lens attachment as it resulted in considerable loss of image quality at twice the zoom. Using a 20 D lens helped attain higher magnification and better framing as it reduced the focussing distance needed to get sharp images. The images obtained from both smartphones were of higher quality when illuminated from an external source when compared to the native iPhone flash due to even exposure and fewer autofocus artefacts. CONCLUSION: Analyses of all image sets showed that the current generation in-built camera app on IOS and newer iPhone camera optics resulted in high-quality images of the ocular surface with high magnification without any loss in clarity.},
	issn = {1573-2630},
	doi = {10.1007/s10792-020-01598-9},
	author = {Kalra, Gagan and Ichhpujani, Parul and Thakur, Sahil and Singh, Rohan Bir and Sharma, Urvashi and Kumar, Suresh}
}
@article {1782356,
	title = {A versatile pumpless multi-channel fluidics system for maintenance and real-time functional assessment of tissue and cells},
	journal = {Cell Rep Methods},
	volume = {3},
	number = {11},
	year = {2023},
	month = {2023 Nov 20},
	pages = {100642},
	abstract = {To address the needs of the life sciences community and the pharmaceutical industry in pre-clinical drug development to both maintain and continuously assess tissue metabolism and function with simple and rapid systems, we improved on the initial BaroFuse to develop it into a fully functional, pumpless, scalable multi-channel fluidics instrument that continuously measures changes in oxygen consumption and other endpoints in response to test compounds. We and several other laboratories assessed it with a wide range of tissue types including retina, pancreatic islets, liver, and hypothalamus with both aqueous and gaseous test compounds. The setup time was less than an hour for all collaborating groups, and there was close agreement between data obtained from the different laboratories. This easy-to-use system reliably generates real-time metabolic and functional data from tissue and cells in response to test compounds that will address a critical need in basic and applied research.},
	keywords = {Gases, Insulin Secretion, Islets of Langerhans, Oxygen, Oxygen Consumption},
	issn = {2667-2375},
	doi = {10.1016/j.crmeth.2023.100642},
	author = {Kamat, Varun and Grumbine, Matthew K and Bao, Khang and Mokate, Kedar and Khalil, Gamal and Cook, Daniel and Clearwater, Brandon and Hirst, Richard and Harman, Jarrod and Boeck, Myriam and Fu, Zhongjie and Smith, Lois E H and Goswami, Moloy and Wubben, Thomas J and Walker, Emily M and Zhu, Jie and Soleimanpour, Scott A and Scarlett, Jarrad M and Robbings, Brian M and Hass, Daniel and Hurley, James B and Sweet, Ian R}
}
@article {509121,
	title = {Protective effect of soft contact lenses after Boston keratoprosthesis.},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {549-52},
	abstract = {PURPOSE: To evaluate associations between preoperative diagnosis, soft contact lens (SCL) retention and complications. METHODS: A retrospective chart review was conducted of 92 adult patients (103 eyes) who received a Boston keratoprosthesis type I at the Massachusetts{\textquoteright}s Eye and Ear Infirmary or the Flaum Eye Institute. Records were reviewed for preoperative diagnosis, SCL retention and subsequent complications. Preoperative categories included 16 autoimmune (Stevens-Johnson syndrome, ocular cicatricial pemphigoid, rheumatoid arthritis and uveitis), 9 chemical injury and 67 {\textquoteright}other{\textquoteright} (aniridia, postoperative infection, dystrophies, keratopathies) patients. RESULTS: 50\% of the lenses had been lost the first time after about a year. A subset (n=17) experienced more than 2 SCL losses per year; this group is comprised of 1 patient with autoimmune diseases, 2 patients with chemical injuries and 14 patients with {\textquoteright}other{\textquoteright} diseases. The preoperative diagnosis was not predictive of contact lens retention. However, multivariate analysis demonstrated that the absence of a contact lens was an independent risk factor for postoperative complications, such as corneal melts with or without aqueous humour leak/extrusion and infections. CONCLUSIONS: Presence of a contact lens after Boston keratoprosthesis implantation decreases the risk of postoperative complications; this has been clinically experienced by ophthalmologists, but never before has the benefit of contact lens use in this patient population been statistically documented.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-306396},
	author = {Kammerdiener, Leah L and Speiser, Jaime Lynn and Aquavella, James V and Harissi-Dagher, Mona and Dohlman, Claes H and Chodosh, James and Ciolino, Joseph B}
}
@article {397811,
	title = {High-irradiance CXL combined with myopic LASIK: flap and residual stroma biomechanical properties studied ex-vivo.},
	journal = {Br J Ophthalmol},
	volume = {99},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {870-4},
	abstract = {BACKGROUND/AIMS: To evaluate ex vivo biomechanical and enzymatic digestion resistance differences between standard myopic laser in-situ keratomileusis (LASIK) compared with LASIK+CXL, in which high-irradiance cross-linking (CXL) is added. METHODS: Eight human donor corneas were subjected to femtosecond-assisted myopic LASIK. Group A (n=4) served as a control group (no CXL). The corneas in LASIK+CXL group B were subjected to concurrent prophylactic high-irradiance CXL (n=4). Saline-diluted (0.10\%) riboflavin was instilled on the stroma, subsequently irradiated with UV-A through the repositioned flap. The cornea stroma and flap specimens were separately subjected to transverse biaxial resistance measurements; biomechanical differences were assessed via stress and Young{\textquoteright}s shear modulus. Subsequently, the specimens were subjected to enzymatic degradation. RESULTS: For the corneal stroma specimen, stress at 10\% strain was 128{\textpm}11 kPa for control group A versus 293{\textpm}20 kPa for the LASIK+CXL group B (relative difference Δ=+129\%, p\&lt;0.05). The stress in group B was also increased at 20\% strain by +68\% (p\&lt;0.05). Shear modulus in group B was increased at 10\% strain by +79\%, and at 20\% strain by +48\% (both statistically significant, p\&lt;0.05). The enzymatic degradation time to dissolution was 157.5{\textpm}15.0 min in group A versus 186.25{\textpm}7.5 min in group B (Δ=+18\%, p=0.014). For the flaps, both biomechanical, as well as enzymatic degradation tests showed no significant differences. CONCLUSIONS: LASIK+CXL appears to provide significant increase in underlying corneal stromal rigidity, up to +130\%. Additionally, there is significant relevant enzymatic digestion resistance confirmatory to the above. LASIK flaps appear unaffected biomechanically by the LASIK+CXL procedure, suggesting effective CXL just under the flap.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-306411},
	author = {Kanellopoulos, Anastasios John and Asimellis, George and Salvador-Culla, Borja and Chodosh, James and Ciolino, Joseph B}
}
@article {1647899,
	title = {Cohort Study of Race/Ethnicity and Incident Primary Open-Angle Glaucoma Characterized by Autonomously Determined Visual Field Loss Patterns},
	journal = {Transl Vis Sci Technol},
	volume = {11},
	number = {7},
	year = {2022},
	month = {2022 Jul 08},
	pages = {21},
	abstract = {Purpose: We evaluated racial/ethnic differences in primary open-angle glaucoma (POAG) defined by machine-learning-derived regional visual field (VF) loss patterns. Methods: Participants (N = 209,036) from the Nurses{\textquoteright} Health Study (NHS; 1980-2018), Nurses{\textquoteright} Health Study II (NHS2; 1989-2019), and Health Professionals Follow-Up Study (HPFS; 1986-2018) who were >=40 years of age and free of glaucoma were followed biennially. Incident POAG cases (n = 1946) with reproducible VF loss were confirmed with medical records. Total deviation information from the earliest reliable glaucomatous VF for each POAG eye (n = 2564) was extracted, and machine learning analyses were used to identify optimal solutions ("archetypes") for regional VF loss patterns. Each POAG eye was assigned a VF archetype based on the highest weighting coefficient. Multivariable-adjusted hazard ratios (HRs) and 95\% confidence intervals (CIs) were estimated using per-eye Cox proportional hazards models. Results: We identified 14 archetypes: four representing advanced loss patterns, nine of early loss, and one of no VF loss. Compared to non-Hispanic whites, black participants had higher risk of early VF loss archetypes (HR = 1.98; 95\% CI, 1.48-2.66) and even higher risk for advanced loss archetypes (HR = 6.17; 95\% CI, 3.69-10.32; P-contrast = 0.0002); no differences were observed for Asians or Hispanic whites. Hispanic white participants had significantly higher risks of POAG with paracentral defects and advanced superior loss; black participants had significantly higher risks of all advanced loss archetypes and three early loss patterns, including paracentral defects. Conclusions: Blacks, compared to non-Hispanic whites, had higher risks of POAG with early central and advanced VF loss. Translational Relevance: In POAG, risks of VF loss regional patterns derived from machine learning algorithms showed racial differences.},
	keywords = {Cohort Studies, ethnicity, Follow-Up Studies, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Vision Disorders, Visual Fields},
	issn = {2164-2591},
	doi = {10.1167/tvst.11.7.21},
	author = {Kang, Jae H and Wang, Mengyu and Frueh, Lisa and Rosner, Bernard and Wiggs, Janey L and Tobias Elze and Pasquale, Louis R}
}
@article {1354356,
	title = {Relation between time spent outdoors and exfoliation glaucoma or exfoliation glaucoma suspect},
	journal = {Am J Ophthalmol},
	volume = {158},
	number = {3},
	year = {2014},
	month = {2014 Sep},
	pages = {605-14.e1},
	abstract = {PURPOSE: To evaluate the relation between time spent outdoors at various life periods and risk of exfoliation glaucoma or exfoliation glaucoma suspect. DESIGN: Retrospective cohort study in the United States. METHODS: Participants (49 033 women in the Nurses Health Study and 20 066 men in the Health Professionals Follow-up Study) were 60+ years old, were free of glaucoma and cataract, reported eye examinations, and completed questions about time spent outdoors in direct sunlight at midday at 3 life periods: high school to age 24 years, age 25-35 years, and age 36-59 years (asked in 2006 in women and 2008 in men). Participants were followed biennially with mailed questionnaires from 1980 women/1986 men to 2010. Incident cases (223 women and 38 men) were confirmed with medical records. Cohort-specific multivariable-adjusted rate ratios from Cox proportional hazards models were estimated and pooled with meta-analysis. RESULTS: Although no association was observed with greater time spent outdoors in the ages of 25-35 or ages 36-59 years, the pooled multivariable-adjusted rate ratios for >=11 hours per week spent outdoors in high school to age 24 years compared with <=5 hours per week was 2.00 (95\% confidence interval\&nbsp;= 1.30, 3.08; P for linear trend\&nbsp;= .001). In women, this association was stronger in those who resided in the southern geographic tier in young adulthood (P for interaction\&nbsp;= .07). CONCLUSIONS: Greater time spent outdoors in young adulthood was associated with risk of exfoliation glaucoma or exfoliation glaucoma suspect, supporting an etiologic role of early exposures to climatic factors.},
	keywords = {Adult, Aged, Environment, Exfoliation Syndrome, Female, Follow-Up Studies, Humans, Incidence, Intraocular Pressure, Leisure Activities, Male, Middle Aged, Ocular Hypertension, Proportional Hazards Models, Retrospective Studies, Risk Factors, Surveys and Questionnaires, Time Factors, United States, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.05.015},
	author = {Kang, Jae H and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1483607,
	title = {Regional Hyperexcitability and Chronic Neuropathic Pain Following Spinal Cord Injury},
	journal = {Cell Mol Neurobiol},
	volume = {40},
	number = {6},
	year = {2020},
	month = {2020 Aug},
	pages = {861-878},
	abstract = {Spinal cord injury (SCI) causes maladaptive changes to nociceptive synaptic circuits within the injured spinal cord. Changes also occur at remote regions including the brain stem, limbic system, cortex, and dorsal root ganglia. These maladaptive nociceptive synaptic circuits frequently cause neuronal hyperexcitability in the entire nervous system and enhance nociceptive transmission, resulting in chronic central neuropathic pain following SCI. The underlying mechanism of chronic neuropathic pain depends on the neuroanatomical structures and electrochemical communication between pre- and postsynaptic neuronal membranes, and propagation of synaptic transmission in the ascending pain pathways. In the nervous system, neurons are the only cell type that transmits nociceptive signals from peripheral receptors to supraspinal systems due to their neuroanatomical and electrophysiological properties. However, the entire range of nociceptive signaling is not mediated by any single neuron. Current literature describes regional studies of electrophysiological or neurochemical mechanisms for enhanced nociceptive transmission post-SCI, but few studies report the electrophysiological, neurochemical, and neuroanatomical changes across the entire nervous system following a regional SCI. We, along with others, have continuously described the enhanced nociceptive transmission in the spinal dorsal horn, brain stem, thalamus, and cortex in SCI-induced chronic central neuropathic pain condition, respectively. Thus, this review summarizes the current understanding of SCI-induced neuronal hyperexcitability and maladaptive nociceptive transmission in the entire nervous system that contributes to chronic central neuropathic pain.},
	issn = {1573-6830},
	doi = {10.1007/s10571-020-00785-7},
	author = {Kang, Jonghoon and Cho, Steve S and Kim, Hee Young and Lee, Bong Hyo and Cho, Hee Jung and Gwak, Young S}
}
@article {1677781,
	title = {Comparison of Perimetric Outcomes from a Tablet Perimeter, Smart Visual Function Analyzer, and Humphrey Field Analyzer},
	journal = {Ophthalmol Glaucoma},
	volume = {6},
	number = {5},
	year = {2023},
	month = {2023 Sep-Oct},
	pages = {509-520},
	abstract = {PURPOSE: The tablet-based Melbourne Rapid Fields (MRF) visual field (VF) test and the IMOvifa Smart Visual Function Analyzer (SVFA) are portable perimeters that may allow for at-home monitoring and more frequent testing. We compared tablet and SVFA results with outputs from the Humphrey Field Analyzer (HFA) 24-2 Swedish Interactive Threshold Algorithm Standard program. DESIGN: Observational cross-sectional study. SUBJECTS: Adult participants with a diagnosis of glaucoma, suspected glaucoma, or ocular hypertension seen in the Massachusetts Eye and Ear glaucoma clinic were enrolled. All participants were reliable and experienced HFA testers. METHODS: Participants were tested with the SVFA and HFA. The study staff also trained participants on the MRF tablet with instructions to take weekly tests at home for 3 months. Visual field results from the 3 devices were compared. MAIN OUTCOME MEASURES: Mean deviation (MD), pattern standard deviation (PSD), reliability parameters, and point sensitivity. RESULTS: Overall, 79 participants (133 eyes) with a mean age of 61\&nbsp;{\textpm}\&nbsp;13 years (range, 26-79 years) were included; 59\% of the participants were female, and the mean HFA MD was\&nbsp;-2.7\&nbsp;{\textpm}\&nbsp;3.9 dB. The global indices of MD and PSD did not significantly vary between HFA and the 2 novel devices, except that the tablet VF reported a 0.6 dB higher PSD compared with HFA. However, tablet and SVFA sensitivities significantly differed from those of the HFA at 36 and 39 locations, respectively, out of 52 locations. Relative to HFA, the tablet overestimated light sensitivity in the nasal field while underestimating the temporal field. The SVFA generally underestimated light sensitivity, but its results were more similar to HFA results compared with the tablet. CONCLUSIONS: Although average MD values from the 2 novel devices suggest that they provide similar results to the HFA, point-by-point comparisons highlight notable deviations. Differences in specific point sensitivity values were significant, especially between the tablet and the other 2 devices. These differences may in part be explained by differences in the devices{\textquoteright} normative databases as well as how MD is calculated. However, the tablet had substantial differences based on location, indicating that the tablet design itself may be responsible for differences in local sensitivities. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2023.03.001},
	author = {Kang, Joyce and De Arrigunaga, Sofia and Freeman, Sandra E and Zhao, Yan and Lin, Michael and Liebman, Daniel L and Roldan, Ana M and Kim, Julia A and Chang, Dolly S and Friedman, David S and Tobias Elze}
}
@article {1498242,
	title = {Cohort Study of Non-melanoma Skin Cancer and the Risk of Exfoliation Glaucoma},
	journal = {J Glaucoma},
	year = {2020},
	month = {2020 Mar 20},
	abstract = {PRECIS: In a cohort study of 120,307 participants with 25+ years of follow-up, a history of non-melanoma skin cancer was associated with a 40\% higher exfoliation glaucoma risk. PURPOSE: To evaluate the relationship between non-melanoma skin cancer (a marker of ultraviolet radiation exposure) and exfoliation glaucoma (XFG). METHODS: We performed a cohort study of US women (n=79,102; 1980-2014) and men (n=41,205; 1986-2014), aged 40+ years and at risk for glaucoma who reported eye exams. From 1984 (women)/1988 (men), we asked about basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) history separately; in prior years, we asked about any non-melanoma skin cancer history in a single question. SCC was confirmed with histopathology reports while BCC and any early (\&lt;1984/\&lt;1988) non-melanoma skin cancer history was self-reported. Incident XFG cases (362 women and 83 men) were confirmed with medical records. Using pooled data, we estimated multivariable-adjusted relative risks (MVRR; 95\% confidence intervals [CIs]) with Cox proportional hazards models that were stratified by age (in months), 2-year time period at risk and average lifetime residential latitude. RESULTS: In multivariable-adjusted analyses, we observed a 40\% higher XFG risk with any non-melanoma skin cancer history (MVRR=1.40; 95\% CI=1.08,1.82); the association was observed even with 4 and 8 year lags in non-melanoma skin cancer history. Also, the non-melanoma skin cancer association was stronger in younger (\&lt;65▒y; MVRR=2.56; 95\% CI=1.62,4.05) versus older participants (>=65▒y; MVRR=1.25; 95\% CI=0.94,1.66; p for interaction=0.01) and those living in northern latitudes (>=42{\textdegree} north; MVRR=1.92; 95\% CI=1.28,2.88) versus more southern latitudes (\&lt;42{\textdegree} north; MVRR=1.19; 95\% CI=0.86,1.66; p for interaction=0.04). CONCLUSIONS: Non-melanoma skin cancer was associated with higher XFG risk, particularly among younger participants and those living in Northern US.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001496},
	author = {Kang, Jae H and VoPham, Trang and Laden, Francine and Rosner, Bernard A and Wirostko, Barbara and Ritch, Robert and Wiggs, Janey L and Qureshi, Abrar and Nan, Hongmei and Pasquale, Louis R}
}
@article {1651352,
	title = {Prediagnostic Plasma Metabolomics and the Risk of Exfoliation Glaucoma},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2022},
	author = {Kang, J H and Zeleznik, O and Frueh, L and Lasky-Su, J and Eliassen, AH and Clish, C and Rosner, BA and Pasquale, L. R. and Wiggs, J L}
}
@article {1354357,
	title = {Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma},
	journal = {Eye (Lond)},
	volume = {28},
	number = {6},
	year = {2014},
	month = {2014 Jun},
	pages = {662-71},
	abstract = {AIMS: Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. METHODS: We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the {\textquoteright}Pathway Analysis by Randomization Incorporating Structure{\textquoteright} analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. RESULTS: The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P>=0.20). In gene-based analyses, eight were associated with POAG overall at permuted P\&lt;0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P\&lt;0.001, whereas none of the six genes reached P\&lt;0.001 for peripheral loss only. DISCUSSION: Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.},
	keywords = {Aged, AMP-Activated Protein Kinases, Case-Control Studies, Caveolin 1, Dynamins, Endothelium, Vascular, Female, Genetic Predisposition to Disease, Genotype, Glaucoma, Open-Angle, GTP-Binding Proteins, Humans, Inositol 1,4,5-Trisphosphate Receptors, Intraocular Pressure, Male, Middle Aged, Muscle, Smooth, Vascular, Nitric Oxide Synthase Type III, Polymorphism, Single Nucleotide, Receptor, Endothelin B, Receptors, Endothelin, Signal Transduction},
	issn = {1476-5454},
	doi = {10.1038/eye.2014.42},
	author = {Kang, J H and Loomis, S J and Yaspan, B L and Bailey, J C and Weinreb, R N and Lee, R K and Lichter, P R and Budenz, D L and Liu, Y. and Realini, T and Gaasterland, D and Gaasterland, T and Friedman, D S and McCarty, C A and Moroi, S E and Olson, L and Schuman, J S and Singh, K and Vollrath, D and Wollstein, G and Zack, D J and Brilliant, M and Sit, A J and Christen, W G and Fingert, J and Forman, J P and Buys, E S and Kraft, P and Zhang, K and Allingham, R R and Pericak-Vance, M A and Richards, J E and Hauser, M A and Haines, J L and Wiggs, J L and Pasquale, L. R.}
}
@article {397816,
	title = {Comparison of risk factor profiles for primary open angle glaucoma subtypes defined by pattern of visual field loss: a prospective study.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2015},
	month = {2015 Mar 10},
	abstract = {PURPOSE: We explored whether risk factor associations differed by primary open-angle glaucoma (POAG) subtypes defined by visual field (VF) loss pattern (i.e., paracentral or peripheral). METHODS: We included 77,157 women in the Nurses Health Study and 42,773 men in the Health Professionals Follow-up Study (1986-2010) and incident medical-record confirmed cases of paracentral (n=440) and peripheral (n=865) POAG subtypes. We evaluated African-heritage, glaucoma family history, body mass index (BMI), mean arterial blood pressure, diabetes mellitus, physical activity, smoking, caffeine and alcohol intakes. We used competing risk Cox regression analyses modeling age as the metameter and stratified by age, cohort and event type. We sequentially identified factors with the least significant differences in associations with POAG subtypes ("stepwise down" approach with P for heterogeneity [P-het]\&lt;0.10 as threshold). RESULTS: BMI was more inversely associated with the POAG paracentral VF loss subtype than the peripheral VF loss subtype (per 10 kg/m2; hazard ratio [HR]=0.67 [95\% Confidence Interval [CI]: 0.52, 0.86] vs. HR=0.93 [95\% CI: 0.78, 1.10]; P-het=0.03) as was smoking (per 10 pack-years; HR=0.92 [95\% CI: 0.87, 0.98] vs. HR=0.98 [95\% CI: 0.94, 1.01]; P-het=0.09). These findings were robust in sensitivity analyses using a "stepwise up" approach (identify factors that showed the most significant differences). Non-heterogeneous (p-het\&gt;0.10) adverse associations with both POAG subtypes were observed with glaucoma family history, diabetes, African-heritage, greater caffeine intake and higher mean arterial pressure. CONCLUSIONS: These data indicate that POAG with early paracentral VF loss has distinct as well as common determinants compared to POAG with peripheral VF loss.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-16088},
	author = {Kang, Jae H and Loomis, Stephanie J and Rosner, Bernard A and Wiggs, Janey L and Pasquale, Louis R}
}
@article {560216,
	title = {Author Response: Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: True Risk Factors or Arbituary Definition?},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {11},
	year = {2015},
	month = {2015 Oct 1},
	pages = {6532-3},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17944},
	author = {Kang, Jae H and Loomis, Stephanie J and Rosner, Bernard A and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1498253,
	title = {Notice of Retraction and Replacement. Kang et al. Association of statin use and high serum cholesterol levels with risk of primary open-angle glaucoma. JAMA Ophthalmol. 2019;137(7):756-765},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Mar 12},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.0027},
	author = {Kang, Jae H and Boumenna, Tahani and Stein, Joshua D and Khawaja, Anthony and Rosner, Bernard A and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1517183,
	title = {Cohort Study of Nonmelanoma Skin Cancer and the Risk of Exfoliation Glaucoma},
	journal = {J Glaucoma},
	volume = {29},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {448-455},
	abstract = {PRECIS: In a cohort study of 120,307 participants with 25+ years of follow-up, a history of nonmelanoma skin cancer (NMSC) was associated with a 40\% higher exfoliation glaucoma (XFG) risk. PURPOSE: The purpose of this study was to evaluate the relationship between NMSC (a marker of ultraviolet radiation exposure) and XFG. METHODS: We performed a cohort study of US women (n=79,102; 1980-2014) and men (n=41,205; 1986-2014), aged 40+ years and at risk for glaucoma who reported eye examinations. From 1984 (women)/1988 (men), we asked about basal cell carcinoma or squamous cell carcinoma history separately; in prior years, we asked about any NMSC history in a single question. Squamous cell carcinoma was confirmed with histopathology reports while basal cell carcinoma and any early (\&lt;1984/\&lt;1988) NMSC history was self-reported. Incident XFG cases (362 women and 83 men) were confirmed with medical records. Using pooled data, we estimated multivariable-adjusted relative risks [MVRRs; 95\% confidence intervals (CIs)] with Cox proportional hazards models that were stratified by age (in mo), 2-year time period at risk and average lifetime residential latitude. RESULTS: In multivariable-adjusted analyses, we observed a 40\% higher XFG risk with any NMSC history (MVRR=1.40; 95\% CI=1.08-1.82); the association was observed even with 4 and 8-year lags in NMSC history. Also, the NMSC association was stronger in younger (below 65 y; MVRR=2.56; 95\% CI=1.62-4.05) versus older participants (65 y and above; MVRR=1.25; 95\% CI=0.94-1.66; P for interaction=0.01) and those living in the northern latitudes (>=42{\textdegree}N; MVRR=1.92; 95\% CI=1.28-2.88) versus more southern latitudes (\&lt;42{\textdegree}N; MVRR=1.19; 95\% CI=0.86-1.66; P for interaction=0.04). CONCLUSION: NMSC was associated with higher XFG risk, particularly among younger participants and those living in the Northern US.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001496},
	author = {Kang, Jae H and VoPham, Trang and Laden, Francine and Rosner, Bernard A and Wirostko, Barbara and Ritch, Robert and Wiggs, Janey L and Qureshi, Abrar and Nan, Hongmei and Pasquale, Louis R}
}
@article {1318865,
	title = {Sex hormone levels and risk of primary open-angle glaucoma in postmenopausal women},
	journal = {Menopause},
	volume = {25},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {1116-1123},
	abstract = {OBJECTIVE: We evaluated the relation of prediagnostic sex hormone levels in postmenopausal women with primary open-angle glaucoma (POAG) and intraocular pressure (IOP). METHODS: Among postmenopausal participants of the Nurses{\textquoteright} Health Study, POAG cases (n = 189; diagnosed 1990-2008) and controls (n = 189) were matched on age, fasting status, and postmenopausal hormone use at blood draw (1989-1990). Plasma concentrations of estrone sulfate, estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate were assessed. The primary outcome was POAG; in secondary analyses, among cases only, we evaluated maximum untreated IOP at diagnosis. Multivariable-adjusted logistic/multiple linear regression models were used to evaluate tertiles (Ts) of biomarker levels and the two outcomes, adjusting for various potential confounders. RESULTS: We observed no significant associations of estrone, estradiol, sex hormone binding globulin, or dehydroepiandrosterone sulfate with POAG risk or with maximum IOP at glaucoma diagnosis among cases. Suggestive significant associations were observed with highest testosterone and POAG risk (T3 vs T1 multivariable-adjusted odds ratio 1.84; 95\% confidence interval 1.02, 3.33; P trend 0.10). Similarly, for maximum IOP at diagnosis among cases only (mean 8 years after blood draw), higher testosterone was significantly associated with higher IOP (multivariable-adjusted difference in IOP T3 vs T1 2.17 mm Hg; 95\% confidence interval 0.34, 3.99; P trend 0.02). CONCLUSIONS: Overall, plasma sex hormone levels in postmenopausal women were not associated with POAG risk; however, a trend of higher testosterone levels being associated with higher POAG risk and higher IOP at diagnosis was observed and needs confirmation.},
	issn = {1530-0374},
	doi = {10.1097/GME.0000000000001120},
	author = {Kang, Jae Hee and Rosner, Bernard A and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1363128,
	title = {Regulation of SPARC by transforming growth factor β2 in human trabecular meshwork},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {4},
	year = {2013},
	month = {2013 Apr 05},
	pages = {2523-32},
	abstract = {PURPOSE: An increased aqueous level of TGF-β2 has been found in many primary open-angle glaucoma patients. Secreted Protein, Acidic, and Rich in Cysteine (SPARC)-null mice have a lower intraocular pressure. The mechanistic relationship between SPARC and TGF-β2 in trabecular meshwork (TM) is unknown. We hypothesized that TGF-β2 upregulates SPARC expression in TM. METHODS: Cultured TM cells were incubated with selective inhibitors for p38 MAP kinase (p38), Smad3, p42, JNK, RhoA, PI3K, or TGF-β2 receptor for 2 hours, and then TGF-β2 was added for 24 hours in serum-free media. Quantitative polymerase chain reaction (qPCR) and immunoblot analysis were performed. Immunofluorescent microscopy was used to determine nuclear translocation of signaling proteins. Ad5.hSPARC and Lentiviral shRNA for p38 and Smad3 were constructed, and infected human TM cells. RESULTS: SPARC was upregulated by TGF-β2 in the human TM cells (3.8 {\textpm} 1.7-fold, n = 6, P = 0.01 for protein and 7.1 {\textpm} 3.7-fold, n = 6, P = 0.01 for mRNA), while upregulation of SPARC had no effect on TGF-β2. TGF-β2-induced SPARC expression was suppressed by inhibitors against p38 (-40.3 {\textpm} 20.9\%, n = 10, P = 0.0001), Smad3 (-56.2 {\textpm} 18.9\%, n = 10, P = 0.0001), JNK (-49.1 {\textpm} 24.6\%, n = 10, P = 0.0001), and TGF-β2 receptor (-83.6 {\textpm} 14.4\%, n = 6, P = 0.003). Phosphorylation and translocation of Smad3, p38, and MAPKAPK2 were detected at 30 minutes and 1 hour, respectively, following TGF-β2 treatment. Phosphorylation of JNK and c-jun was detected before TGF-β2 treatment. SPARC was suppressed 31 {\textpm} 13\% (n = 5, P \&lt; 0.0001) by shRNA-p38 and 41 {\textpm} 3\% (n = 5, P \&lt; 0.0001) by shRNA-Smad3. CONCLUSIONS: TGF-β2 upregulates SPARC expression in human TM through Smad-dependent (Smad2/3) or -independent (p38) signaling pathways. SPARC may be a downstream regulatory node of TGF-β2-mediated IOP elevation.},
	keywords = {Adenoviridae, Adult, Aged, Cells, Cultured, Child, Enzyme Inhibitors, Fluorescent Antibody Technique, Indirect, Humans, Immunoblotting, MAP Kinase Signaling System, Middle Aged, Osteonectin, Phosphorylation, Real-Time Polymerase Chain Reaction, RNA, Messenger, Smad2 Protein, Smad3 Protein, Trabecular Meshwork, Transfection, Transforming Growth Factor beta2, Tumor Suppressor Proteins, Up-Regulation},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-11474},
	author = {Kang, Min Hyung and Oh, Dong-Jin and Kang, Ja-heon and Rhee, Douglas J}
}
@article {836896,
	title = {Contribution of the Nurses{\textquoteright} Health Study to the Epidemiology of Cataract, Age-Related Macular Degeneration, and Glaucoma.},
	journal = {Am J Public Health},
	volume = {106},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1684-9},
	abstract = {OBJECTIVES: To review the contribution of the Nurses{\textquoteright} Health Study (NHS) to understanding the genetic and lifestyle factors that influence the risk of cataract, age-related macular degeneration, and glaucoma. METHODS: We performed a narrative review of the publications of the NHS between 1976 and 2016. RESULTS: The NHS has helped to elucidate the roles of genetics, lifestyle factors (e.g., cigarette smoking associated with cataract extraction and age-related macular degeneration), medical conditions (e.g., diabetes associated with cataract extraction and glaucoma), and dietary factors (e.g., greater carotenoid intake and lower glycemic diet associated with lower risk of age-related macular degeneration) in the etiology of degree and progression of lens opacities, cataract extraction, age-related macular degeneration, primary open-angle glaucoma, and exfoliation glaucoma. CONCLUSIONS: The findings from the NHS, combined with those of other studies, have provided compelling evidence to support public health recommendations for helping to prevent age-related eye diseases: abstinence from cigarette smoking, maintenance of healthy weight and diabetes prevention, and a healthy diet rich in fruits and vegetables.},
	issn = {1541-0048},
	doi = {10.2105/AJPH.2016.303317},
	author = {Kang, Jae H and Wu, Juan and Cho, Eunyoung and Ogata, Soshiro and Jacques, Paul and Taylor, Allen and Chiu, Chung-Jung and Wiggs, Janey L and Seddon, Johanna M and Hankinson, Susan E and Schaumberg, Debra A and Pasquale, Louis R}
}
@article {1439851,
	title = {Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 May 02},
	abstract = {Importance: The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG. Objective: To assess the association of elevated cholesterol levels and statin use with incident POAG. Design, Setting, and Participants: This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses{\textquoteright} Health Study (N = 50 710; followed up from 2000 to 2014), the Nurses{\textquoteright} Health Study 2 (N = 62 992; 1999-2015), and the Health Professionals Follow-up Study (N = 23 080; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January 2019. Exposures: Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use. Main Outcomes and Measures: Multivariable-adjusted relative risks (RRs) and 95\% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort. Results: Among the 136 782 participants in the 3 cohorts (113 702 women and 23 080 men), 886 incident cases of POAG were identified. Every 20-mg/dL increase in total serum cholesterol was associated with a 7\% increase in risk of POAG (RR, 1.07 [95\% CI, 1.02-1.11]; P = .004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95\% CI, 1.00-1.37]). A history of any statin use was associated with a 15\% lower risk of POAG (RR, 0.85 [95\% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21\% lower risk of POAG (RR, 0.79 [95\% CI, 0.65-0.97]; P = .02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (>=65 years: RR, 0.70 [95\% CI, 0.56-0.87] vs \&lt;65 years: RR, 1.05 [95\% CI, 0.68-1.63]; P = .01 for interaction). Conclusions and Relevance: Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.0900},
	author = {Kang, Jae H and Boumenna, Tahani and Stein, Joshua D and Khawaja, Anthony and Rosner, Bernard A and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1363129,
	title = {Pharmacogenetics of the treatment response of age-related macular degeneration with ranibizumab and bevacizumab},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {355-60},
	abstract = {INTRODUCTION: Age-related macular degeneration is a major cause of blindness among people aged 50 and older in industrialized countries. Anti-VEGF therapy has been tremendously successful in the treatment of neovascular macular degeneration. Examining the pharmacogenetics of patients{\textquoteright} response to the anti-VEGF molecules could allow for a tailored treatment strategy based on patients{\textquoteright} underlying genetics rather than the "one-size fits all" approach currently used. METHODS: Review of the English literature for papers examining the pharmacogenetics of treatment response of neovascular macular degeneration to either ranibizumab or bevacizumab. Polymorphisms in CFH, ARMS2, HTRA1 and VEGF A were examined and reviewed. RESULTS: Patients with the high-risk CC genotype in complement factor H (CFH) had a worse response to therapy with ranibizumab and bevacizumab. No clear trends were found with ARMS2, HTRA1 and VEGF A. CONCLUSIONS: The goal of personalized medicine is to craft a treatment program that is ideally suited to an individual patient{\textquoteright}s disease and genetic make-up rather than simply what works for a large population who share similar disease characteristics. Continued research is needed to achieve this goal for the treatment of age-related macular degeneration.},
	keywords = {Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Bevacizumab, Complement Factor H, High-Temperature Requirement A Serine Peptidase 1, Humans, Macular Degeneration, Pharmacogenetics, Precision Medicine, Proteins, Ranibizumab, Serine Endopeptidases, Treatment Outcome, Vascular Endothelial Growth Factor A},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825292},
	author = {Kanoff, Justin and Miller, Joan}
}
@article {1593860,
	title = {Nerve Growth Factor as an Ocular Therapy: Applications, Challenges, and Future Directions},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {224-231},
	abstract = {Nerve growth factor (NGF), the prototypical neurotrophin first discovered in the 1950s, has recently garnered increased interest as a therapeutic agent promoting neuronal health and regeneration. After gaining orphan drug status within the last decade, NGF-related research and drug development has accelerated. The purpose of this article is to review the preclinical and clinical evidence of NGF in various applications, including central and peripheral nervous system, skin, and ophthalmic disorders. We focus on the ophthalmic applications including not only the FDA-approved indication of neurotrophic keratitis but also retinal disease and glaucoma. NGF represents a promising therapy whose therapeutic profile is evolving. The challenges related to this therapy are reviewed, along with possible solutions and future directions.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1890793},
	author = {Kanu, Levi N and Ciolino, Joseph B}
}
@article {1295867,
	title = {ICG-001 Exerts Potent Anticancer Activity Against Uveal Melanoma Cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {1},
	year = {2018},
	month = {2018 Jan 01},
	pages = {132-143},
	abstract = {Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic chemotherapies, thus creating an urgent need for novel therapeutics. In this study, we investigated the sensitivity of UM cells to ICG-001, a small molecule reported to suppress the Wnt/β-catenin-mediated transcriptional program. Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on cellular proliferation, migration, and gene expression. In vivo efficacy of ICG-001 was evaluated in a UM xenograft model. Results: ICG-001 exerted strong antiproliferative activity against UM cells, leading to cell cycle arrest, apoptosis, and inhibition of migration. Global gene expression profiling revealed strong suppression of genes associated with cell cycle proliferation, DNA replication, and G1/S transition. Gene set enrichment analysis revealed that ICG-001 suppressed Wnt, mTOR, and MAPK signaling. Strikingly, ICG-001 suppressed the expression of genes associated with UM aggressiveness, including CDH1, CITED1, EMP1, EMP3, SDCBP, and SPARC. Notably, the transcriptomic footprint of ICG-001, when applied to a UM patient dataset, was associated with better clinical outcome. Lastly, ICG-001 exerted anticancer activity against a UM tumor xenograft in mice. Conclusions: Using in vitro and in vivo experiments, we demonstrate that ICG-001 has strong anticancer activity against UM cells and suppresses transcriptional programs critical for the cancer cell. Our results suggest that ICG-001 holds promise and should be examined further as a novel therapeutic agent for UM.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-22454},
	author = {Kaochar, Salma and Dong, Jianrong and Torres, Marie and Rajapakshe, Kimal and Nikolos, Fotis and Davis, Christel M and Ehli, Erik A and Coarfa, Cristian and Mitsiades, Nicholas and Poulaki, Vasiliki}
}
@article {1363130,
	title = {TGF-β3 stimulates stromal matrix assembly by human corneal keratocyte-like cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {10},
	year = {2013},
	month = {2013 Oct 09},
	pages = {6612-9},
	abstract = {PURPOSE: We have previously shown that TGF-β3 (T3) stimulates extracellular matrix (ECM) assembly while maintaining antifibrotic characteristics in a model using human corneal fibroblasts (HCFs). This model, however, requires non-physiological levels of serum. In the current study, we tested whether T3 could stimulate human corneal keratocytes (HCKs) in vitro to assemble a functional ECM, while maintaining their characteristics. METHODS: Human corneal keratocytes and HCFs were isolated and cultured using 1\% or 10\% serum, respectively {\textpm}T3. The constructs were processed for indirect immunofluorescence (IF), transmission electron microscopy (TEM), and qRT-PCR, analyzing for keratocyte marker, keratocan, and ECM components, collagen (col) types I, III, and V. RESULTS: Quantitative reverse transcriptase PCR data showed that keratocan, col I, and V were all upregulated in HCKs compared with HCFs, whereas col III was expressed at low levels in HCKs. Transforming growth factor beta 3 stimulation further enhanced the level of change. Without T3, HCK constructs were very thin, approximately 5 μm; however, as with HCFs, upon stimulation with T3, HCK constructs increased in thickness by approximately 5-fold. Cell counts and ECM production revealed that HCKs assembled more ECM per unit area compared with HCFs, and IF revealed downregulation of fibrotic markers, col III, and thrombospondin-1, with T3 stimulation. Transmission electron microscopy data revealed aligned ECM with long fibrils for all conditions except HCK Controls. Human corneal keratocytes+T3 also showed denser collagen fibrils with more consistent fibril diameter. CONCLUSIONS: Overall, the data suggests that it is possible to stimulate matrix secretion and assembly by HCKs in vitro by using a single growth factor, T3.},
	keywords = {Biomarkers, Cells, Cultured, Corneal Keratocytes, Extracellular Matrix, Fibroblasts, Humans, Microscopy, Electron, Transmission, Reverse Transcriptase Polymerase Chain Reaction, Transforming Growth Factor beta3},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12861},
	author = {Karamichos, Dimitrios and Rich, Celeste B and Zareian, Ramin and Hutcheon, Audrey E K and Ruberti, Jeffrey W and Trinkaus-Randall, Vickery and Zieske, James D}
}
@article {313216,
	title = {Reversal of fibrosis by TGF-β3 in a 3D in~vitro model},
	journal = {Exp Eye Res},
	volume = {124},
	year = {2014},
	month = {2014 Jul},
	pages = {31-6},
	abstract = {Corneal scarring following moderate to severe injury is inevitable. Despite significant advancements in the field, current treatments following these types of injuries are limited, and often, the visual recovery is poor. One of the problems and limitations is that corneal wound healing is a complex process, involving corneal cells, extracellular matrix components and growth factors. Therefore, further understanding is required, along with new treatments and techniques to reduce or prevent corneal scarring following injury. Two isoforms of transforming growth factor-beta (TGF-β), TGF-β1 and -β3 (T1 and T3, respectively), are associated with corneal wound healing. T1 has been shown to drive the corneal keratocytes to differentiate into myofibroblasts; whereas, T3 has been found to inhibit fibrotic markers. In the current study, we examined whether the fibrotic characteristics expressed by human corneal fibroblasts (HCF) in our 3-dimensional (3D) construct following T1 stimulation could be reversed by introducing T3 to the in~vitro system. To do this, HCF were isolated and cultured in 10\% serum, and when they reached confluence, the cells were stimulated with a stable Vitamin C (VitC) derivative for 4 weeks, which allowed them to secrete a self-assembled matrix. Three conditions were tested: (1) CONTROL: 10\% serum (S) only, (2) T1: 10\%S~+~T1, or (3) Rescue: 10\%S~+~T1 for two weeks and then switched to 10\%S~+~T3 for another two weeks. At the end of 4 weeks, the constructs were processed for analysis by indirect-immunofluorescence (IF) and transmission electron microscopy (TEM). Different collagens that are normally present in healthy corneas in~vivo, such as Type I and V, as well as Type III, which is a fibrotic indicator, were examined. In addition, we examined smooth muscle actin (SMA), a marker of myofibroblasts, and thrombospondin-1 (TSP-1), a multifunctional matrix protein known to activate the latent complex of TGF-β and appear upon wounding in~vivo. Our data showed high expression of collagens type I and V under all conditions throughout the 3D constructs; however, type III and SMA expression were higher in the constructs that were stimulated with T1 and reduced to almost nothing in the Rescue samples. A similar pattern was seen with TSP-1, where TSP-1 expression following "rescue" was decreased considerably. Overall, this data is in agreement with our previous observations that T3 has a significant non-fibrotic effect on HCFs, and presents a novel model for the "rescue" of both cellular and matrix fibrotic components with a single growth factor. },
	keywords = {Actins, Antibodies, Cells, Cultured, Corneal Diseases, Corneal Keratocytes, Extracellular Matrix, Fibrosis, Fluorescent Antibody Technique, Indirect, Humans, Microscopy, Electron, Transmission, Transforming Growth Factor beta3},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2014.04.020},
	author = {Karamichos, D and Hutcheon, A E K and Zieske, J D}
}
@article {1354358,
	title = {In vitro model suggests oxidative stress involved in keratoconus disease},
	journal = {Sci Rep},
	volume = {4},
	year = {2014},
	month = {2014 Apr 09},
	pages = {4608},
	abstract = {Keratoconus (KC) affects 1:2000 people and is a disorder where cornea thins and assumes a conical shape. Advanced KC requires surgery to maintain vision. The role of oxidative stress in KC remains unclear. We aimed to identify oxidative stress levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs). Cells were cultured in 2D and 3D systems. Vitamin C (VitC) and TGF-β3 (T3) were used for 4 weeks to stimulate self-assembled extracellular matrix (ECM). No T3 used as controls. Samples were analyzed using qRT-PCR and metabolomics. qRT-PCR data showed low levels of collagen I and V, as well as keratocan for HKCs, indicating differentiation to a myofibroblast phenotype. Collagen type III, a marker for fibrosis, was up regulated in HKCs. We robustly detected more than 150 metabolites of the targeted 250 by LC-MS/MS per condition and among those metabolites several were related to oxidative stress. Lactate levels, lactate/malate and lactate/pyruvate ratios were elevated in HKCs, while arginine and glutathione/oxidized glutathione ratio were reduced. Similar patterns found in both 2D and 3D. Our data shows that fibroblasts exhibit enhanced oxidative stress compared to keratocytes. Furthermore the HKC cells exhibit the greatest level suggesting they may have a myofibroblast phenotype.},
	keywords = {Arginine, Ascorbic Acid, Cell Differentiation, Cells, Cultured, Collagen Type I, Collagen Type III, Collagen Type IV, Cornea, Corneal Keratocytes, Extracellular Matrix, Fibroblasts, Glutathione, Humans, Keratoconus, Lactic Acid, Malates, Metabolomics, Myofibroblasts, Oxidative Stress, Proteoglycans, Pyruvic Acid, Transforming Growth Factor beta3},
	issn = {2045-2322},
	doi = {10.1038/srep04608},
	author = {Karamichos, D and Hutcheon, A E K and Rich, C B and Trinkaus-Randall, V and Asara, J M and Zieske, J D}
}
@article {369071,
	title = {Tear metabolite changes in keratoconus.},
	journal = {Exp Eye Res},
	volume = {132},
	year = {2015},
	month = {2015 Mar},
	pages = {1-8},
	abstract = {While efforts have been made over the years, the exact cause of keratoconus (KC) remains unknown. The aim of this study was to identify alterations in endogenous metabolites in the tears of KC patients compared with age-matched healthy subjects. Three groups were tested: 1) Age-matched controls with no eye disease (N\&nbsp;=\&nbsp;15), 2) KC - patients wearing Rigid Gas permeable lenses (N\&nbsp;=\&nbsp;16), and 3) KC - No Correction (N\&nbsp;=\&nbsp;14). All samples were processed for metabolomics analysis using LC-MS/MS. We identified a total of 296 different metabolites of which \&gt;40 were significantly regulated between groups. Glycolysis and gluconeogenesis had significant changes, such as 3-phosphoglycerate and 1,3 diphosphateglycerate. As a result the citric acid cycle (TCA) was also affected with notable changes in Isocitrate, aconitate, malate, and acetylphosphate, up regulated in Group 2 and/or 3. Urea cycle was also affected, especially in Group 3 where ornithine and aspartate were up-regulated by at least 3 fold. The oxidation state was also severely affected. Groups 2 and 3 were under severe oxidative stress causing multiple metabolites to be regulated when compared to Group 1. Group 2 and 3, both showed significant down regulation in GSH-to-GSSG ratio when compared to Group 1. Another indicator of oxidative stress, the ratio of lactate - pyruvate was also affected with Groups 2 and 3 showing at least a 2-fold up regulation. Overall, our data indicate that levels of metabolites related to urea cycle, TCA cycle and oxidative stress are highly altered in KC patients.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2015.01.007},
	author = {Karamichos, D and Zieske, J D and Sejersen, H and Sarker-Nag, A and Asara, John M and Hjortdal, J}
}
@article {1364621,
	title = {Novel  Model for Keratoconus Disease},
	journal = {J Funct Biomater},
	volume = {3},
	number = {4},
	year = {2012},
	month = {2012 Nov 13},
	pages = {760-775},
	abstract = {Keratoconus is a disease where the cornea becomes cone-like due to structural thinning and ultimately leads to compromised corneal integrity and loss of vision. Currently, the therapeutic options are corrective lenses for early stages and surgery for advanced cases with no  model available. In this study, we used human corneal fibroblasts (HCFs) and compared them to human Keratoconus fibroblasts (HKCs) cultured in a 3-dimensional (3D) model, in order to compare the expression and secretion of specific extracellular matrix (ECM) components. For four weeks, the cells were stimulated with a stable Vitamin C (VitC) derivative {\textpm} TGF-β1 or TGF-β3 (T1 and T3, respectively). After four weeks, HKCs stimulated with T1 and T3 were significantly thicker compared with Control (VitC only); however, HCF constructs were significantly thicker than HKCs under all conditions. Both cell types secreted copious amounts of type I and V collagens in their assembled, aligned collagen fibrils, which increased in the degree of alignment upon T3 stimulation. In contrast, only HKCs expressed high levels of corneal scarring markers, such as type III collagen, which was dramatically reduced with T3. HKCs expressed α-smooth muscle actin (SMA) under all conditions in contrast to HCFs, where T3 minimized SMA expression. Fast Fourier transform (FFT) data indicated that HKCs were more aligned when compared to HCFs, independent of treatments; however, HKC{\textquoteright}s ECM showed the least degree of rotation. HKCs also secreted the most aligned type I collagen under T3 treatment, when compared to any condition and cell type. Overall, our model for Keratoconus disease studies is the first 3D  tissue engineered model that can mimic the Keratoconus disease  and may be a breakthrough in efforts to understand the progression of this disease.},
	issn = {2079-4983},
	doi = {10.3390/jfb3040760},
	author = {Karamichos, Dimitrios and Zareian, Ramin and Guo, Xiaoqing and Hutcheon, Audrey E K and Ruberti, Jeffrey W and Zieske, James D}
}
@article {1354359,
	title = {A role for topographic cues in the organization of collagenous matrix by corneal fibroblasts and stem cells},
	journal = {PLoS One},
	volume = {9},
	number = {1},
	year = {2014},
	month = {2014},
	pages = {e86260},
	abstract = {Human corneal fibroblasts (HCF) and corneal stromal stem cells (CSSC) each secrete and organize a thick stroma-like extracellular matrix in response to different substrata, but neither cell type organizes matrix on tissue-culture polystyrene. This study compared cell differentiation and extracellular matrix secreted by these two cell types when they were cultured on identical substrata, polycarbonate Transwell filters. After 4 weeks in culture, both cell types upregulated expression of genes marking differentiated keratocytes (KERA, CHST6, AQP1, B3GNT7). Absolute expression levels of these genes and secretion of keratan sulfate proteoglycans were significantly greater in CSSC than HCF. Both cultures produced extensive extracellular matrix of aligned collagen fibrils types I and V, exhibiting cornea-like lamellar structure. Unlike HCF, CSSC produced little matrix in the presence of serum. Construct thickness and collagen organization was enhanced by TGF-{\ss}3. Scanning electron microscopic examination of the polycarbonate membrane revealed shallow parallel grooves with spacing of 200-300 nm, similar to the topography of aligned nanofiber substratum which we previously showed to induce matrix organization by CSSC. These results demonstrate that both corneal fibroblasts and stromal stem cells respond to a specific pattern of topographical cues by secreting highly organized extracellular matrix typical of corneal stroma. The data also suggest that the potential for matrix secretion and organization may not be directly related to the expression of molecular markers used to identify differentiated keratocytes.},
	keywords = {Cell Differentiation, Cells, Cultured, Collagen, Cornea, Corneal Keratocytes, Corneal Stroma, Corneal Topography, Cues, Extracellular Matrix, Fibroblasts, Humans, Keratan Sulfate, Stem Cells, Transforming Growth Factor beta3},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0086260},
	author = {Karamichos, Dimitrios and Funderburgh, Martha L and Hutcheon, Audrey E K and Zieske, James D and Du, Yiqin and Wu, Jian and Funderburgh, James L}
}
@article {1782416,
	title = {Correction: Microglia preserve visual function in the aging retina by supporting retinal pigment epithelial health},
	journal = {Immun Ageing},
	volume = {20},
	number = {1},
	year = {2023},
	month = {2023 Nov 11},
	pages = {60},
	issn = {1742-4933},
	doi = {10.1186/s12979-023-00388-y},
	author = {Karg, Margarete M and Moorefield, May and Hoffmann, Emma and Philipose, Hannah and Krasniqi, Drenushe and Hoppe, Cindy and Shu, Daisy Y and Shirahama, Shintaro and Ksander, Bruce R and Saint-Geniez, Magali}
}
@article {1773526,
	title = {Microglia preserve visual function loss in the aging retina by supporting retinal pigment epithelial health},
	journal = {Immun Ageing},
	volume = {20},
	number = {1},
	year = {2023},
	month = {2023 Oct 14},
	pages = {53},
	abstract = {BACKGROUND: Increased age is a risk factor for the development and progression of retinal diseases including age-related macular degeneration (AMD). Understanding the changes that occur in the eye due to aging is important in enhancing our understanding of AMD pathogenesis and the development of novel AMD therapies. Microglia, the resident brain and retinal immune cells are associated with both maintaining homeostasis and protection of neurons and loss of microglia homeostasis could be a significant player in age related neurodegeneration. One important characteristic of retinal aging is the migration of microglia from the inner to outer retina where they reside in the subretinal space (SRS) in contact with the retinal pigment epithelial (RPE) cells. The role of aged subretinal microglia is unknown. Here, we depleted microglia in aged C57/BL6 mice fed for 6\&nbsp;weeks with a chow containing PLX5622, a small molecule inhibitor of colony-stimulating factor-1 receptor (Csf1r) required for microglial survival. RESULTS: The subretinal P2RY12 + microglia in aged mice displayed a highly amoeboid and activated morphology and were filled with autofluorescence droplets reminiscent of lipofuscin. TEM indicates that subretinal microglia actively phagocytize shed photoreceptor outer segments, one of the main functions of retinal pigmented epithelial cells. PLX5622 treatment depleted up to 90\% of the retinal microglia and was associated with significant loss in visual function. Mice on the microglia depletion diet showed reduced contrast sensitivity and significantly lower electroretinogram for the c-wave, a measurement of RPE functionality, compared to age-matched controls. The loss of c-wave coincided with a loss of RPE cells and increased RPE swelling in the absence of microglia. CONCLUSIONS: We conclude that microglia preserve visual function in aged mice and support RPE cell function, by phagocytosing shed photoreceptor outer segments and lipids, therefore compensating for the known age-related decline of RPE phagocytosis.},
	issn = {1742-4933},
	doi = {10.1186/s12979-023-00358-4},
	author = {Karg, Margarete M and Moorefield, May and Hoffmann, Emma and Philipose, Hannah and Krasniqi, Drenushe and Hoppe, Cindy and Shu, Daisy Y and Shirahama, Shintaro and Ksander, Bruce R and Saint-Geniez, Magali}
}
@article {1642024,
	title = {Midkine promotes metastasis and therapeutic resistance via mTOR/RPS6 in uveal melanoma},
	journal = {Mol Cancer Res},
	year = {2022},
	month = {2022 May 03},
	abstract = {Uveal melanoma is a rare form of melanoma that originates in the eye, exerts widespread therapeutic resistance and displays an inherent propensity for hepatic metastases. Since metastatic disease is characterized by poor survival, there is an unmet clinical need to identify new therapeutic targets in uveal melanoma. Here, we show that the pleiotropic cytokine midkine is expressed in uveal melanoma. Midkine expression in primary uveal melanoma significantly correlates with poor survival and is elevated in patients that develop metastatic disease. Monosomy 3 and histopathological staging parameters are associated with midkine expression. In addition, we demonstrate that midkine promotes survival, migration across a barrier of hepatic sinusoid endothelial cells and resistance to AKT/mTOR inhibition. Furthermore, midkine is secreted and mediates mTOR activation by maintaining phosphorylation of the mTOR target RPS6 in uveal melanoma cells. Therefore, midkine is identified as a uveal melanoma cell survival factor that drives metastasis and therapeutic resistance, and could be exploited as a biomarker as well as a new therapeutic target. Implications: Midkine is identified as a survival factor that drives liver metastasis and therapeutic resistance in melanoma of the eye.},
	issn = {1557-3125},
	doi = {10.1158/1541-7786.MCR-20-0692},
	author = {Karg, Margarete M and John, Lukas and Refaian, Nasrin and Buettner, Christian and Rottmar, Tanja and Sommer, Jonas and Bock, Barbara and Resheq, Yazid J and Ksander, Bruce R and Heindl, Ludwig M and Mackensen, Andreas and Bosch, Jacobus J}
}
@article {1789156,
	title = {Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma},
	journal = {Cell Reprogram},
	volume = {25},
	number = {6},
	year = {2023},
	month = {2023 Dec},
	pages = {288-299},
	abstract = {Glaucoma, a chronic neurodegenerative disease, is a leading cause of age-related blindness worldwide and characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Previously, we developed a novel epigenetic rejuvenation therapy, based on the expression of the three transcription factors Oct4, Sox2, and Klf4 (OSK), which safely rejuvenates RGCs without altering cell identity in glaucomatous and old mice after 1 month of treatment. In the current year-long study, mice with continuous or cyclic OSK expression induced after glaucoma-induced vision damage had occurred were tracked for efficacy, duration, and safety. Surprisingly, only 2 months of OSK fully restored impaired vision, with a restoration of vision for 11 months with prolonged expression. In RGCs, transcription from the doxycycline (DOX)-inducible Tet-On AAV system, returned to baseline 4 weeks after DOX withdrawal. Significant vision improvements remained for 1 month post switching off OSK, after which the vision benefit gradually diminished but remained better than baseline. Notably, no adverse effects on retinal structure or body weight were observed in glaucomatous mice with OSK continuously expressed for 21 months providing compelling evidence of efficacy and safety. This work highlights the tremendous therapeutic potential of rejuvenating gene therapies using OSK, not only for glaucoma but also for other ocular and systemic injuries and age-related diseases.},
	keywords = {Animals, Disease Models, Animal, Genetic Therapy, Glaucoma, Intraocular Pressure, Mice, Neurodegenerative Diseases, Retina},
	issn = {2152-4998},
	doi = {10.1089/cell.2023.0074},
	author = {Karg, Margarete M and Lu, Yuancheng Ryan and Refaian, Nasrin and Cameron, James and Hoffmann, Emma and Hoppe, Cindy and Shirahama, Shintaro and Shah, Madhura and Krasniqi, Drenushe and Krishnan, Anitha and Shrestha, Maleeka and Guo, Yinjie and Cermak, Jennifer M and Walthier, Michel and Broniowska, Kasia and Rosenzweig-Lipson, Sharon and Gregory-Ksander, Meredith and Sinclair, David A and Ksander, Bruce R}
}
@article {560241,
	title = {Transcriptional Regulation of the Astrocytic Excitatory Amino Acid Transporter 1 (EAAT1) via NF-κB and Yin Yang 1 (YY1).},
	journal = {J Biol Chem},
	volume = {290},
	number = {39},
	year = {2015},
	month = {2015 Sep 25},
	pages = {23725-37},
	abstract = {Astrocytic glutamate transporter excitatory amino acid transporter (EAAT) 1, also known as glutamate aspartate transporter (GLAST) in rodents, is one of two glial glutamate transporters that are responsible for removing excess glutamate from synaptic clefts to prevent excitotoxic neuronal death. Despite its important role in neurophysiological functions, the molecular mechanisms of EAAT1 regulation at the transcriptional level remain to be established. Here, we report that NF-κB is a main positive transcription factor for EAAT1, supported by the following: 1) EAAT1 contains two consensus sites for NF-κB, 2) mutation of NF-κB binding sites decreased EAAT1 promoter activity, and 3) activation of NF-κB increased, whereas inhibition of NF-κB decreased EAAT1 promoter activity and mRNA/protein levels. EGF increased EAAT1 mRNA/protein levels and glutamate uptake via NF-κB. The transcription factor yin yang 1 (YY1) plays a role as a critical negative regulator of EAAT1, supported by the following: 1) the EAAT1 promoter contains multiple consensus sites for YY1, 2) overexpression of YY1 decreased EAAT1 promoter activity and mRNA/protein levels, and 3) knockdown of YY1 increased EAAT1 promoter activity and mRNA/protein levels. Manganese decreased EAAT1 expression via YY1. Epigenetic modifiers histone deacetylases (HDACs) served as co-repressors of YY1 to further decrease EAAT1 promoter activity, whereas inhibition of HDACs reversed manganese-induced decrease of EAAT1 expression. Taken together, our findings suggest that NF-κB is a critical positive regulator of EAAT1, mediating the stimulatory effects of EGF, whereas YY1 is a negative regulator of EAAT1 with HDACs as co-repressors, mediating the inhibitory effects of manganese on EAAT1 regulation.},
	issn = {1083-351X},
	doi = {10.1074/jbc.M115.649327},
	author = {Karki, Pratap and Kim, Clifford and Smith, Keisha and Son, Deok-Soo and Aschner, Michael and Lee, Eunsook}
}
@article {1364622,
	title = {c-Met modulates RPE migratory response to laser-induced retinal injury},
	journal = {PLoS One},
	volume = {7},
	number = {7},
	year = {2012},
	month = {2012},
	pages = {e40771},
	abstract = {Retinal laser injuries are often associated with aberrant migration of the retinal pigment epithelium (RPE), which can cause expansion of the scar beyond the confines of the original laser burn. In this study, we devised a novel method of laser-induced injury to the RPE layer in mouse models and began to dissect the mechanisms associated with pathogenesis and progression of laser-induced RPE injury. We have hypothesized that the proto-oncogene receptor, c-Met, is intimately involved with migration of RPE cells, and may be an early responder to injury. Using transgenic mouse models, we show that constitutive activation of c-Met induces more robust RPE migration into the outer retina of laser-injured eyes, while abrogation of the receptor using a cre-lox method reduces these responses. We also demonstrate that retinal laser injury increases expression of both HGF and c-Met, and activation of c-Met after injury is correlated with RPE cell migration. RPE migration may be responsible for clinically significant anatomic changes observed after laser injury. Abrogation of c-Met activity may be a therapeutic target to minimize retinal damage from aberrant RPE cell migration.},
	keywords = {Animals, Apoptosis, Burns, Cell Movement, Epithelial Cells, Gene Expression Regulation, Hepatocyte Growth Factor, In Situ Nick-End Labeling, Integrases, Lasers, Mice, Mice, Inbred C57BL, Mice, Knockout, Proto-Oncogene Proteins c-met, Retinal Pigment Epithelium, RNA, Messenger},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0040771},
	author = {Kasaoka, Masataka and Ma, Jie and Lashkari, Kameran}
}
@article {1603876,
	title = {HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV},
	journal = {Cell Rep},
	volume = {36},
	number = {2},
	year = {2021},
	month = {2021 Jul 13},
	pages = {109378},
	abstract = {Defining factors that govern CD8+ T\&nbsp;cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T\&nbsp;cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2021.109378},
	author = {Kaseke, Clarety and Park, Ryan J and Singh, Nishant K and Koundakjian, Dylan and Bashirova, Arman and Garcia Beltran, Wilfredo F and Takou Mbah, Overbeck C and Ma, Jiaqi and Senjobe, Fernando and Urbach, Jonathan M and Nathan, Anusha and Rossin, Elizabeth J and Tano-Menka, Rhoda and Khatri, Ashok and Piechocka-Trocha, Alicja and Waring, Michael T and Birnbaum, Michael E and Baker, Brian M and Carrington, Mary and Walker, Bruce D and Gaiha, Gaurav D}
}
@article {1761896,
	title = {Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {10},
	year = {2023},
	month = {2023 Oct 01},
	pages = {956-964},
	abstract = {IMPORTANCE: Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies. OBJECTIVE: To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants. DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)-derived inner retinal layer thicknesses. Data analysis was conducted in January 2023. EXPOSURE: Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse. MAIN OUTCOMES AND MEASURES: The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell-inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively. RESULTS: This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1\%) were women. There were 33 175 CCB users (7.8\%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95\% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (-0.34 μm [95\% CI, -0.54 to -0.15 μm]; P = .001) and mRNFL (-0.16 μm [95\% CI, -0.30 to -0.02 μm]; P = .03) thicknesses but not IOP (-0.01 mm Hg [95\% CI, -0.09 to 0.07 mm Hg]; P = .84). CONCLUSIONS AND RELEVANCE: In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39\% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.3877},
	author = {Kastner, Alan and Stuart, Kelsey V and Montesano, Giovanni and De Moraes, C Gustavo and Kang, Jae H and Wiggs, Janey L and Pasquale, Louis R and Hysi, Pirro and Chua, Sharon Y L and Patel, Praveen J and Foster, Paul J and Khaw, Peng T and Khawaja, Anthony P and UK Biobank Eye and Vision Consortium}
}
@article {416861,
	title = {Macrophage- and RIP3-dependent inflammasome activation exacerbates retinal detachment-induced photoreceptor cell death.},
	journal = {Cell Death Dis},
	volume = {6},
	year = {2015},
	month = {2015},
	pages = {e1731},
	abstract = {Detachment of photoreceptors from the retinal pigment epithelium is seen in various retinal disorders, resulting in photoreceptor death and subsequent vision loss. Cell death results in the release of endogenous molecules that activate molecular platforms containing caspase-1, termed inflammasomes. Inflammasome activation in retinal diseases has been reported in some cases to be protective and in others to be detrimental, causing neuronal cell death. Moreover, the cellular source of inflammasomes in retinal disorders is not clear. Here, we demonstrate that patients with photoreceptor injury by retinal detachment (RD) have increased levels of cleaved IL-1β, an end product of inflammasome activation. In an animal model of RD, photoreceptor cell death led to activation of endogenous inflammasomes, and this activation was diminished by Rip3 deletion. The major source of Il1b expression was found to be infiltrating macrophages in the subretinal space, rather than dying photoreceptors. Inflammasome inhibition attenuated photoreceptor death after RD. Our data implicate the infiltrating macrophages as a source of damaging inflammasomes after photoreceptor detachment in a RIP3-dependent manner and suggest a novel therapeutic target for treatment of retinal diseases.},
	issn = {2041-4889},
	doi = {10.1038/cddis.2015.73},
	author = {Kataoka, K and Matsumoto, H and Kaneko, H and Notomi, S and Takeuchi, K. and Sweigard, J H and Atik, A and Murakami, Y and Connor, K M and Terasaki, H and Miller, J W and Vavvas, D G}
}
@article {1302193,
	title = {NQO1 downregulation potentiates menadione-induced endothelial-mesenchymal transition during rosette formation in Fuchs endothelial corneal dystrophy},
	journal = {Free Radic Biol Med},
	volume = {116},
	year = {2018},
	month = {2018 Feb 20},
	pages = {19-30},
	abstract = {Fuchs endothelial corneal dystrophy (FECD) is a genetic and oxidative stress disorder of post-mitotic human corneal endothelial cells (HCEnCs), which normally exhibit hexagonal shape and form a compact monolayer compatible with normal corneal functioning and clear vision. FECD is associated with increased DNA damage, which in turn leads to HCEnC loss, resulting in the formation rosettes and aberrant extracellular matrix (ECM) deposition in the form of pro-fibrotic guttae. Since the mechanism of ECM deposition in FECD is currently unknown, we aimed to investigate the role of endothelial-mesenchymal transition (EMT) in FECD using a previously established cellular in vitro model that recapitulates the characteristic rosette formation, by employing menadione (MN)-induced oxidative stress. We demonstrate that MN treatment alone, or a combination of MN and TGF-β1 induces reactive oxygen species (ROS), cell death, and EMT in HCEnCs during rosette formation, resulting in upregulation of EMT- and FECD-associated markers such as Snail1, N-cadherin, ZEB1, and transforming growth factor-beta-induced (TGFβI), respectively. Additionally, FECD ex vivo specimens displayed a loss of organized junctional staining of plasma membrane-bound N-cadherin, with corresponding increase in fibronectin and Snail1 compared to ex vivo controls. Addition of N-acetylcysteine (NAC) downregulated all EMT markers and abolished rosette formation. Loss of NQO1, a metabolizing enzyme of MN, led to greater increase in intracellular ROS levels as well as a significant upregulation of Snail1, fibronectin, and N-cadherin compared to normal cells, indicating that NQO1 regulates Snail1-mediated EMT. This study provides first line evidence that MN-induced oxidative stress leads to EMT in corneal endothelial cells, and the effect of which is further potentiated when redox cycling activity of MN is enhanced by the absence of NQO1. Given that NAC inhibits Snail-mediated EMT, this may be a potential therapeutic intervention for FECD.},
	issn = {1873-4596},
	doi = {10.1016/j.freeradbiomed.2017.12.036},
	author = {Katikireddy, Kishore Reddy and White, Tomas L and Miyajima, Taiga and Vasanth, Shivakumar and Raoof, Duna and Chen, Yuming and Price, Marianne O and Price, Francis W and Jurkunas, Ula V}
}
@article {931096,
	title = {Existence of Neural Crest-Derived Progenitor Cells in Normal and Fuchs Endothelial Dystrophy Corneal Endothelium.},
	journal = {Am J Pathol},
	volume = {186},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {2736-50},
	abstract = {Human corneal endothelial cells are derived from neural crest and because of postmitotic arrest lack competence to repair cell loss from trauma, aging, and degenerative disorders such as Fuchs endothelial corneal dystrophy (FECD). Herein, we identified a rapidly proliferating subpopulation of cells from the corneal endothelium of adult normal and FECD donors that exhibited features of neural crest-derived progenitor (NCDP) cells by showing absence of senescence with passaging, propensity to form spheres, and increased colony forming efficacy compared with the primary cells. The collective expression of stem cell-related genes SOX2, OCT4, LGR5, TP63 (p63), as well as neural crest marker genes PSIP1 (p75(NTR)), PAX3, SOX9, AP2B1 (AP-2β), and NES, generated a phenotypic footprint of endothelial NCDPs. NCDPs displayed multipotency by differentiating into microtubule-associated protein 2, β-III tubulin, and glial fibrillary acidic protein positive neurons and into p75(NTR)-positive human corneal endothelial cells that exhibited transendothelial resistance of functional endothelium. In conclusion, we found that mitotically incompetent ocular tissue cells contain adult NCDPs that exhibit a profile of transcription factors regulating multipotency and neural crest progenitor characteristics. Identification of normal NCDPs in FECD-affected endothelium holds promise for potential autologous cell therapies.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2016.06.011},
	author = {Katikireddy, Kishore Reddy and Schmedt, Thore and Price, Marianne O and Price, Francis W and Jurkunas, Ula V}
}
@article {397821,
	title = {Limbal Stromal Tissue Specific Stem Cells and Their Differentiation Potential to Corneal Epithelial Cells.},
	journal = {Methods Mol Biol},
	volume = {1341},
	year = {2016},
	month = {2016},
	pages = {437-44},
	abstract = {From the derivation of the first human embryonic stem (hES) cell line to the development of induced pluripotent stem (iPS) cells; it has become evident that tissue specific stem cells are able to differentiate into a specific somatic cell types. The understanding of key processes such as the signaling pathways and the role of the microenvironment in epidermal/epithelial development has provided important clues for the derivation of specific epithelial cell types.Various differentiation protocols/methods were used to attain specific epithelial cell types. Here, we describe in detail the procedure to follow for isolation of tissue specific stem cells, mimicking their microenvironment to attain stem cell characteristics, and their potential differentiation to corneal epithelial cells.},
	issn = {1940-6029},
	doi = {10.1007/7651_2015_229},
	author = {Katikireddy, Kishore Reddy and Jurkunas, Ula V}
}
@article {1661843,
	title = {Efficient cardiac gene transfer and early-onset expression of a synthetic adeno-associated viral vector, Anc80L65, after intramyocardial administration},
	journal = {J Thorac Cardiovasc Surg},
	volume = {164},
	number = {6},
	year = {2022},
	month = {2022 Dec},
	pages = {e429-e443},
	abstract = {OBJECTIVE: Gene therapy is a promising approach in the treatment of cardiovascular diseases. Preclinical and clinical studies have demonstrated that adeno-associated viral vectors are the most attractive vehicles for gene transfer. However, preexisting immunity, delayed gene expression, and postinfection immune response limit the success of this technology. The aim of this study was to investigate the efficacy of the first synthetic adeno-associated viral lineage clone, Anc80L65, for cardiac gene therapy. METHODS: By combining 2 different reporter approaches by fluorescence with green fluorescent protein and bioluminescence (Firefly luciferase), we compared transduction efficiency of Anc80L65 and adeno-associated virus, serotype 9 in neonatal rat cardiomyocytes ex\&nbsp;vivo and rat hearts in\&nbsp;vivo after intramyocardial and intracoronary administration. RESULTS: In cardiomyocytes, Anc80L65 provided a green fluorescent protein expression of 28.9\% (36.4\&nbsp;{\textpm}\&nbsp;3.34\&nbsp;cells/field) at 24\&nbsp;hours and approximately 100\% on day 7. In contrast, adeno-associated virus, serotype 9 green fluorescent protein provided minimal green fluorescent protein expression of 5.64\% at 24\&nbsp;hours and 11.8\% on day 7. After intramyocardial injection, vector expression peaked on day 7 with Anc80L65; however, with adeno-associated virus, serotype 9 the peak expression was during week 6. Administration of Anc80L65 demonstrated significantly more efficient expression of reporter gene than after adeno-associated virus, serotype 9 at 6\&nbsp;weeks (6.81\&nbsp;{\textpm}\&nbsp;0.64 log10 gc/100\&nbsp;ng DNA vs 6.49\&nbsp;{\textpm}\&nbsp;0.28 log10 gc/100\&nbsp;ng DNA, P\&nbsp;\&lt;\&nbsp;.05). These results were consistent with the amount of genome copy per cell observed in the heart. CONCLUSIONS: Anc80L65 vector allows fast and robust gene transduction compared with adeno-associated virus, serotype 9 vector in cardiac gene therapy. Anc80L65 did not adversely affect cardiac function and caused no inflammatory response or toxicity.},
	keywords = {Animals, Dependovirus, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Green Fluorescent Proteins, Myocytes, Cardiac, Rats, Transduction, Genetic},
	issn = {1097-685X},
	doi = {10.1016/j.jtcvs.2021.05.050},
	author = {Katz, Michael G and Hadas, Yoav and Bailey, Rasheed A and Fazal, Shahood and Vincek, Adam and Madjarova, Sophia J and Shtraizent, Nataly and Vandenberghe, Luk H and Eliyahu, Efrat}
}
@article {1664960,
	title = {Intraoperative aberrometry: an update on applications and outcomes},
	journal = {Curr Opin Ophthalmol},
	volume = {34},
	number = {1},
	year = {2023},
	month = {2023 Jan 01},
	pages = {48-57},
	abstract = {PURPOSE OF REVIEW: There is now a large body of experience with intraoperative aberrometry. This review aims to synthesize available data regarding intraoperative aberrometry applications and outcomes. RECENT FINDINGS: The Optiwave Refractive Analysis (ORA) System utilizes Talbot-moir{\'e} interferometry and is the only commercially available intraoperative aberrometry device. There are few studies that include all-comers undergoing intraoperative aberrometry-assisted cataract surgery, as most studies examine routine patients only or atypical eyes only. In non-post-refractive cases, studies have consistently shown a small but statistically significant benefit in spherical equivalent refractive outcome for intraoperative aberrometry versus preoperative calculations. In studies examining axial length extremes, most studies have shown intraoperative aberrometry to perform similarly to preoperative calculations. Amongst post-refractive cases, post-myopic ablation cases appear to benefit the most from intraoperative aberrometry. For toric intraocular lenses (IOLs), intraoperative aberrometry may be used for refining IOL power (toricity and spherical equivalent) and alignment, and most studies show intraoperative aberrometry to achieve low postoperative residual astigmatism. SUMMARY: Intraoperative aberrometry can be utilized as an adjunct to preoperative planning and surgeon{\textquoteright}s judgment to optimize cataract surgery refractive outcomes. Non-post-refractive cases, post-myopic ablation eyes, and toric intraocular lenses may have the greatest demonstrated benefit in intraoperative aberrometry studies to date, but other eyes may also benefit from intraoperative aberrometry use.},
	keywords = {Cataract, Humans},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000915},
	author = {Kaufman, Aaron R and Pineda, Roberto}
}
@article {1290016,
	title = {Phacoemulsification with intraocular lens implantation after previous descemetorhexis without endothelial keratoplasty},
	journal = {J Cataract Refract Surg},
	volume = {43},
	number = {11},
	year = {2017},
	month = {2017 Nov},
	pages = {1471-1475},
	abstract = {A 58-year-old woman with bilateral Fuchs endothelial corneal dystrophy presented with predominantly central guttata in the left\&nbsp;eye causing visually significant stromal edema. A 4.0\&nbsp;mm descemetorhexis without endothelial keratoplasty was performed. At the 6-week follow-up, the central cornea had cleared completely and the central endothelial cell density (ECD) was 541\&nbsp;cells/mm2. The central corneal clearing remained stable for 2\&nbsp;years after the procedure; however, vision declined because of a visually significant cataract in the left eye. Uneventful phacoemulsification with intraocular lens implantation was performed with a target refraction of -0.50 diopters. At 1.5\&nbsp;months postoperatively, the uncorrected distance visual acuity was 20/20 with a manifest refraction of -0.25 -0.25\&nbsp;{\texttimes}\&nbsp;60 and the central ECD was 2373\&nbsp;cells/mm2 (increased from 1471\&nbsp;cells/mm2 prior to phacoemulsification). Cataract surgery by phacoemulsification years after descemetorhexis without endothelial keratoplasty appears to be well-tolerated, with good clinical and predictive refractive outcomes.},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2017.10.028},
	author = {Kaufman, Aaron R and Nos{\'e}, Ricardo M and Lu, Yifan and Pineda, Roberto}
}
@article {1282126,
	title = {Clinical Outcomes Using Oversized Back Plates in Type I Boston Keratoprosthesis},
	journal = {Eye Contact Lens},
	volume = {44},
	number = {6},
	year = {2018},
	month = {2018 Nov},
	pages = {399-404},
	abstract = {OBJECTIVES: To examine clinical outcomes of oversized titanium back plates in type I Boston keratoprosthesis (KPro) implantation. METHODS: Retrospective study of 22 sequential eyes (20 patients) undergoing type I KPro implantation with an oversized titanium back plate (larger than trephined wound diameter by 1.0 mm or more), performed by a single surgeon (K.A.C.) from June 2010 to November 2014. Data were collected regarding preoperative eye characteristics, surgical details, and postoperative clinical outcomes. RESULTS: Mean follow-up time per eye was 24.1{\textpm}14.9 months. All eyes had improved vision after surgery; 13 eyes (59.1\%) maintained visual acuity improvement at last follow-up. Initial KPro{\textquoteright}s were retained in 19 eyes (86.4\%); one eye required KPro replacement. Primary retroprosthetic membrane (RPM) developed in three eyes (13.6\%), with similar occurrence in aniridic (14.3\%) and nonaniridic eyes (13.3\%). Secondary RPM{\textquoteright}s developed in two eyes (9.1\%) after vitritis (one eye) and retinal and choroidal detachment (one eye). Glaucoma was a common comorbidity: 2 of 14 eyes (14.3\%) with preoperative glaucoma had glaucoma progression, and 4 of 8 eyes (50.0\%) without preoperative glaucoma developed glaucoma postoperatively. Other postoperative complications included retinal detachment (5 eyes, 22.7\%) and idiopathic vitritis (3 eyes, 13.6\%). CONCLUSIONS: Oversized titanium KPro back plates are associated with a low rate of primary RPM formation and may have particular utility in reducing primary RPM formation in aniridic eyes. Glaucoma remains a challenge in postoperative KPro management. Complex eyes, at increased risk of postoperative complications, require careful management.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000446},
	author = {Kaufman, Aaron R and Cruzat, Andrea and Colby, Kathryn A}
}
@article {1658653,
	title = {Monkeypox Virus and Ophthalmology-A Primer on the 2022 Monkeypox Outbreak and Monkeypox-Related Ophthalmic Disease},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {1},
	year = {2023},
	month = {2023 Jan 01},
	pages = {78-83},
	abstract = {IMPORTANCE: An ongoing global monkeypox virus outbreak in 2022 includes the US and other nonendemic countries. Monkeypox ophthalmic manifestations may present to the ophthalmologist, or the ophthalmologist may be involved in comanagement. This narrative review creates a primer for the ophthalmologist of clinically relevant information regarding monkeypox, its ophthalmic manifestations, and the 2022 outbreak. OBSERVATIONS: Monkeypox virus is an Orthopoxvirus (genus includes variola [smallpox] and vaccinia [smallpox vaccine]). The 2022 outbreak is of clade II (historically named West African clade), specifically subclade IIb. In addition to historic transmission patterns (skin lesions, bodily fluids, respiratory droplets), sexual transmission has also been theorized in the current outbreak due to disproportionate occurrence in men who have sex with men. Monkeypox causes a characteristic skin eruption and mucosal lesions and may cause ophthalmic disease. Monkeypox-related ophthalmic disease (MPXROD) includes a spectrum of ocular pathologies including eyelid/periorbital skin lesions, blepharoconjunctivitis, and keratitis). Smallpox vaccination may reduce MPXROD occurrence. MPXROD seems to be rarer in the 2022 outbreaks than in historical outbreaks. MPXROD may result in corneal scarring and blindness. Historical management strategies for MPXROD include lubrication and prevention/management of bacterial superinfection in monkeypox keratitis. Case reports and in vitro data for trifluridine suggest a possible role in MPXROD. Tecovirimat, cidofovoir, brincidofovir and vaccinia immune globulin intravenous may be used for systemic infection. There is a theoretical risk for monkeypox transmission by corneal transplantation, and the Eye Bank Association of America has provided guidance. Smallpox vaccines (JYNNEOS [Bavarian Nordic] and ACAM2000 [Emergent Product Development Gaithersburg Inc]) provide immunity against monkeypox. CONCLUSIONS AND RELEVANCE: The ophthalmologist may play an important role in the diagnosis and management of monkeypox. MPXROD may be associated with severe ocular and visual morbidity. As the current outbreak evolves, up-to-date guidance from public health organizations and professional societies are critical.},
	keywords = {Disease Outbreaks, Eye Diseases, Homosexuality, Male, Humans, Male, Monkeypox, Monkeypox virus, Ophthalmology, Sexual and Gender Minorities, Smallpox, Vaccinia},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.4567},
	author = {Kaufman, Aaron R and Chodosh, James and Pineda, Roberto}
}
@article {1748466,
	title = {Recurrence of Guttae and Endothelial Dysfunction After Successful Descemet Stripping Only in Fuchs Dystrophy},
	journal = {Cornea},
	volume = {42},
	number = {8},
	year = {2023},
	month = {2023 Aug 01},
	pages = {1037-1040},
	abstract = {PURPOSE: There are limited data about long-term durability of endothelial rejuvenation after Descemet stripping only (DSO). This study reports a case of bilaterally recurrent endothelial dysfunction and guttae formation after initially successful DSO in combination with cataract extraction (DSO-CE). METHODS: This is a retrospective case report. A 49-year-old man with Fuchs endothelial corneal dystrophy with bilateral visually significant endothelial guttae (predominantly confluent centrally) and concomitant cataract underwent DSO-CE bilaterally. Postoperative course to long-term outcome at 6 years was analyzed. RESULTS: Baseline central corneal thickness (CCT) was 568 μm in OD and 582 μm in OS. Preoperatively, both eyes had no countable central endothelial cells but good peripheral endothelial mosaic. In both eyes, the cornea clinically cleared at approximately 1 month postoperatively after DSO-CE. In short-term follow-up (OD postoperative month 6 and OS postoperative month 3), CCT was 556 μm in OD and 561 μm in OS and central endothelial cell density was 1352 cells/mm 2 in OD and 880 cells/mm 2 in OS. The patient returned to our center in postoperative year 6 OU. At this time, OU had interval formation of guttae within the descemetorhexis, with increased CCT (OD 631 μm and OS 609 μm) and decreased central endothelial cell density (OD 728 cells/mm 2 and OS 609 cells/mm 2 ). CONCLUSIONS: After DSO, progressive endothelial dysfunction with new guttae formation can occur within the descemetorhexis region of repopulated endothelium. Larger analyses with longer follow-up are needed to better characterize long-term outcomes of DSO.},
	keywords = {Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelial Cells, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Male, Middle Aged, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003221},
	author = {Kaufman, Aaron R and Bal, Sila and Boakye, Jeffrey and Jurkunas, Ula V}
}
@article {1297781,
	title = {Descemetorhexis Without Endothelial Keratoplasty (DWEK): Proposal for Nomenclature Standardization},
	journal = {Cornea},
	volume = {37},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {e20-e21},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001528},
	author = {Kaufman, Aaron R and Nos{\'e}, Ricardo M and Pineda, Roberto}
}
@article {1789116,
	title = {Wound modulation in glaucoma surgery: The role of anti-scarring agents},
	journal = {Indian J Ophthalmol},
	volume = {72},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {320-327},
	abstract = {Filtration surgery is one of the most frequently performed surgeries in the management of glaucoma, and trabeculectomy is considered the gold standard surgical technique for the same. Though trabeculectomy has been reported to have an excellent initial success rate, about 30\% of them fail in 3 years, and nearly 50\% of them fail in 5 years. The most significant risk of failure still seems to be wound scarring, especially episcleral fibrosis, leading to bleb failure. As a result, it is essential to explore the role of anti-scarring agents, including mitomycin C, and 5-fluorouracil in wound modulation and improving the bleb survival rate. Since these agents are widely used in trabeculectomy, it is crucial to understand the various modes of application, advantages, and adverse effects of these agents. On an evidence-based approach, all these points have been highlighted in this review article. In addition, the newer agents available for wound modulation and their scope for practical application are discussed.},
	keywords = {Cicatrix, Fluorouracil, Glaucoma, Humans, Intraocular Pressure, Mitomycin, Trabeculectomy},
	issn = {1998-3689},
	doi = {10.4103/IJO.IJO_2013_23},
	author = {Kavitha, Srinivasan and Tejaswini, S Usha and Venkatesh, Rengaraj and Zebardast, Nazlee}
}
@article {1430530,
	title = {Resolution of Visual Dysphotopsias after Laser Iridotomy: Six-Month Follow-up},
	journal = {Ophthalmology},
	volume = {126},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {469-471.e1},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.10.014},
	author = {Kavitha, Srinivasan and Ramulu, Pradeep Y and Venkatesh, Rengaraj and Palaniswamy, Krishnamurthy and Kader, Mohideen Abdul and Raman, Ganesh V and Rajendrababu, Sharmila and Zebardast, Nazlee}
}
@article {1402580,
	title = {Resolvin D1, but not resolvin E1, transactivates the epidermal growth factor receptor to increase intracellular calcium and glycoconjugate secretion in rat and human conjunctival goblet cells},
	journal = {Exp Eye Res},
	volume = {180},
	year = {2019},
	month = {2019 Mar},
	pages = {53-62},
	abstract = {PURPOSE: To identify interactions of the epidermal growth factor receptor (EGFR) with the pro-resolving mediator receptors for RvD1 and RvE1 to stimulate an increase in intracellular [Ca] ([Ca]) and mucin secretion from cultured human and rat conjunctival goblet cells. METHODS: Goblet cells from human and rat conjunctiva were grown in culture using RPMI media. Cultured goblet cells were pre-incubated with inhibitors, and then stimulated with RvD1, RvE1, EGF or the cholinergic agonist carbachol (Cch). Increase in [Ca] was measured using fura-2/AM. Goblet cell secretion was measured using an enzyme-linked lectin assay with UEA-1. Western blot analysis was performed with antibodies against AKT and ERK 1/2. RESULTS: In cultured human conjunctival goblet cells RvE1 -stimulated an increase in [Ca]. RvD1-, but not the RvE1-, stimulated increase in [Ca] and mucin secretion was blocked by the EGFR inhibitor AG1478 and siRNA for the EGFR. RvD1-, but not RvE1-stimulated an increase in [Ca] that was also inhibited by TAPI-1, an inhibitor of the matrix metalloprotease ADAM 17. Inhibition of the EGFR also blocked RvD1-stimulated increase in AKT activity and both RvD1-and RvE1-stimulated increase in ERK 1/2 activity. Pretreatment with either RvD1 or RvE1 did not block the EGFR-stimulated increase in [Ca]. CONCLUSIONS: We conclude that in cultured rat and human conjunctival goblet cells, RvD1 activates the EGFR, increases [Ca], activates AKT and ERK1/2 to stimulate mucin secretion. RvE1 does not transactivate the EGFR to increase [Ca] and stimulate mucin secretion, but does interact with the receptor to increase ERK 1/2 activity.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.11.018},
	author = {Kaye, Rebecca and Botten, Nora and Lippestad, Marit and Li, Dayu and Hodges, Robin R and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {416986,
	title = {Lysophosphatidic acid contributes to angiogenic homeostasis.},
	journal = {Exp Cell Res},
	volume = {333},
	number = {2},
	year = {2015},
	month = {2015 May 1},
	pages = {166-170},
	issn = {1090-2422},
	doi = {10.1016/j.yexcr.2014.11.012},
	author = {Kazlauskas, Andrius}
}
@article {303926,
	title = {Plakophilin-2 promotes activation of epidermal growth factor receptor.},
	journal = {Mol Cell Biol},
	volume = {34},
	number = {20},
	year = {2014},
	month = {2014 Oct 15},
	pages = {3778-9},
	abstract = {While growth factor-driven dimerization of receptor tyrosine kinases (RTKs) is a simple and intuitive mechanism of activating RTKs, K.-I. Arimoto et al. (Mol. Cell. Biol. 34:3843-3854, 2014, doi:10.1128/MCB.00758-14) describe a novel means of promoting the activity of RTKs. Namely, plakophilin-2 (PKP2) associates with the epidermal growth factor receptor (EGFR) and enhances its ligand-dependent and ligand-independent activity. This discovery suggests that antagonizing PKP2 may be a new therapeutic opportunity to combat tumors in which activation of EGFR contributes to pathogenesis.},
	issn = {1098-5549},
	doi = {10.1128/MCB.00968-14},
	author = {Kazlauskas, Andrius}
}
@article {1364623,
	title = {Trichosporon asahii keratitis in a patient with a type I Boston keratoprosthesis and contact lens},
	journal = {Eye Contact Lens},
	volume = {38},
	number = {2},
	year = {2012},
	month = {2012 Mar},
	pages = {130-2},
	abstract = {PURPOSE: The aim of the study was to report a case of Trichosporon asahii in a patient with a type I Boston keratoprosthesis and contact lens with review of the literature. METHODS: A case report and literature review are provided. RESULTS: A 70-year-old monocular South Asian man with light perception vision and dense corneal scarring from previously failed amniotic membrane grafting and one failed corneal transplant was evaluated for a keratoprosthesis for visual rehabilitation. Three months after undergoing uneventful implantation of a type I Boston keratoprosthesis and placement of a therapeutic contact lens, he was found on routine follow-up to have a corneal infiltrate that was culture positive for T. asahii. The fungal keratitis was successfully treated with topical amphotericin B and oral ketoconazole. CONCLUSIONS: Contact lens wear is a known risk factor for fungal keratitis. Trichosporon is an uncommon agent of fungal keratitis. We report the first known case of fungal keratitis caused by T.asahii in a patient with a keratoprosthesis and contact lens.},
	keywords = {Aged, Contact Lenses, Eye Infections, Fungal, Humans, Keratitis, Male, Prostheses and Implants, Prosthesis-Related Infections, Trichosporon, Trichosporonosis},
	issn = {1542-233X},
	doi = {10.1097/ICL.0b013e31822c3703},
	author = {Keating, Anne and Pineda, Roberto}
}
@article {1333851,
	title = {Prevalence and causes of vision loss in South-east Asia and Oceania in 2015: magnitude, temporal trends and projections},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {878-884},
	abstract = {BACKGROUND: To assess prevalence and causes of vision impairment in South-east Asia and Oceania regions from 1990 to 2015 and to forecast the figures for 2020. METHODS: Based on a systematic review of medical literature, prevalence of blindness (presenting visual acuity (PVA)\&nbsp;\&lt;3/60 in the better eye), moderate and severe vision impairment (MSVI; PVA\&nbsp;\&lt;6/18 but\&nbsp;>=3/60), mild vision impairment (PVA\&nbsp;\&lt;6/12 but\&nbsp;>=6/18) and near vision impairment (\&gt;N5 or N8 in the presence of normal vision) were estimated for 1990, 2010, 2015 and 2020. RESULTS: The age-standardised prevalence of blindness for all ages and both genders was higher in the Oceania region but lower for MSVI when comparing the subregions. The prevalence of near vision impairment in people>=50 years was 41\% (uncertainty\&nbsp;interval (UI) 18.8\&nbsp;to\&nbsp;65.9). Comparison of the data for 2015 with 2020 predicts a small increase in the numbers of people affected by blindness, MSVI and mild VI in both subregions. The numbers predicted for near VI in South-east Asia are from 90.68 million in 2015 to 102.88 million in 2020. The main causes of blindness and MSVI in both subregions in 2015 were cataract, uncorrected refractive error, glaucoma, corneal disease and age-related macular degeneration. There was no trachoma in Oceania from 1990 and decreasing prevalence in South-east Asia with elimination predicted by 2020. CONCLUSIONS: In both regions, the main challenges for eye care come from cataract which remains the main cause of blindness with uncorrected refractive error the main cause of MSVI. The trend between 1990 and 2015 is for a lower prevalence of blindness and MSVI in both regions.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-311946},
	author = {Keeffe, Jill Elizabeth and Casson, Robert J and Pesudovs, Konrad and Taylor, Hugh R and Cicinelli, Maria Vittoria and Das, Aditi and Flaxman, Seth R and Jonas, Jost B and Kempen, John H and Leasher, Janet and Limburg, Hans and Naidoo, Kovin and Silvester, Alexander J and Stevens, Gretchen A and Tahhan, Nina and Wong, Tien Yin and Resnikoff, Serge and Bourne, Rupert R A and Vision Loss Expert Group of the Global Burden of Disease Study}
}
@article {1528404,
	title = {Strengthening the integration of eye care into the health system: methodology for the development of the WHO package of eye care interventions},
	journal = {BMJ Open Ophthalmol},
	volume = {5},
	number = {1},
	year = {2020},
	month = {2020},
	pages = {e000533},
	abstract = {Objective: To describe the rational for, and the methods that will be employed to develop, the WHO package of eye care interventions (PECI). Methods and analysis: The development of the package will be conducted in four steps: (1) selection of eye conditions (for which interventions will be included in the package) based on epidemiological data on the causes of vision impairment and blindness, prevalence estimates of eye conditions and health facility data; (2) identification of interventions and related evidence for the selected eye conditions from clinical practice guidelines and high-quality systematic reviews by a technical working group; (3) expert agreement on the inclusion of eye care interventions in the package and the description of resources required for the provision of the selected interventions; and (4) peer review. The project will be led by the WHO Vision Programme in collaboration with Cochrane Eyes and Vision. A Technical Advisory Group, comprised of public health and clinical experts in the field, will provide technical input throughout all stages of development. Results: After considering the feedback of Technical Advisory Group members and reviewing-related evidence, a final list of eye conditions for which interventions will be included in the package has been collated. Conclusion: The PECI will support Ministries of Health in prioritising, planning, budgeting and integrating eye care interventions into health systems. It is anticipated that the PECI will be available for use in 2021.},
	issn = {2397-3269},
	doi = {10.1136/bmjophth-2020-000533},
	author = {Keel, Stuart and Evans, Jennifer R and Block, Sandra and Bourne, Rupert and Calonge, Margarita and Cheng, Ching-Yu and Friedman, David S and Furtado, Jo{\~a}o M and Khanna, Rohit C and Mathenge, Wanjiku and Mariotti, Silvio and Matoto, Elenoa and M{\"u}ller, Andreas and Rabiu, M Mansur and Rasengane, Tuwani and Zhao, Jialang and Wormald, Richard and Cieza, Alarcos}
}
@article {1658670,
	title = {Toward Universal Eye Health Coverage-Key Outcomes of the World Health Organization Package of Eye Care Interventions: A Systematic Review},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {12},
	year = {2022},
	month = {2022 Dec 01},
	pages = {1229-1238},
	abstract = {IMPORTANCE: Despite persistent inequalities in access to eye care services globally, guidance on a set of recommended, evidence-based eye care interventions to support country health care planning has not been available. To overcome this barrier, the World Health Organization (WHO) Package of Eye Care Interventions (PECI) has been developed. OBJECTIVE: To describe the key outcomes of the PECI development. EVIDENCE REVIEW: A standardized stepwise approach that included the following stages: (1) selection of priority eye conditions by an expert panel after reviewing epidemiological evidence and health facility data; (2) identification of interventions and related evidence for the selected eye conditions from a systematic review of clinical practice guidelines (CPGs); stage 2 included a systematic literature search, screening of title and abstracts (excluding articles that were not relevant CPGs), full-text review to assess disclosure of conflicts of interest and affiliations, quality appraisal, and data extraction; (3) expert review of the evidence extracted in stage 2, identification of missed interventions, and agreement on the inclusion of essential interventions suitable for implementation in low- and middle-income resource settings; and (4) peer review. FINDINGS: Fifteen priority eye conditions were chosen. The literature search identified 3601 articles. Of these, 469 passed title and abstract screening, 151 passed full-text screening, 98 passed quality appraisal, and 87 were selected for data extraction. Little evidence (<=1 CPG identified) was available for pterygium, keratoconus, congenital eyelid disorders, vision rehabilitation, myopic macular degeneration, ptosis, entropion, and ectropion. In stage 3, domain-specific expert groups voted to include 135 interventions (57\%) of a potential 235 interventions collated from stage 2. After synthesis across all interventions and eye conditions, 64 interventions (13 health promotion and education, 6 screening and prevention, 38 treatment, and 7 rehabilitation) were included in the PECI. CONCLUSIONS AND RELEVANCE: This systematic review of CPGs for priority eye conditions, followed by an expert consensus procedure, identified 64 essential, evidence-based, eye care interventions that are required to achieve universal eye health coverage. The review identified some important gaps, including a paucity of high-quality, English-language CPGs, for several eye diseases and a dearth of evidence-based recommendations on eye health promotion and prevention within existing CPGs.},
	keywords = {Health Promotion, Humans, Universal Health Insurance, World Health Organization},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.4716},
	author = {Keel, Stuart and Lingham, Gareth and Misra, Neha and Block, Sandra and Bourne, Rupert and Calonge, Margarita and Cheng, Ching-Yu and Friedman, David S and Furtado, Jo{\~a}o M and Khanna, Rohit and Mariotti, Silvio and Mathenge, Wanjiku and Matoto, Elenoa and M{\"u}eller, Andreas and Rabiu, Mansur and Rasengane, Tuwani and Resnikoff, Serge and Wormald, Richard and Yasmin, Sumrana and Zhao, Jialiang and Evans, Jennifer R and Cieza, Alarcos and Package of Eye Care Interventions Development Group}
}
@article {1593854,
	title = {Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583},
	journal = {mBio},
	volume = {12},
	number = {3},
	year = {2021},
	month = {2021 May 18},
	abstract = {The alternative sigma factor σ54 has been shown to regulate the expression of a wide array of virulence-associated genes, as well as central metabolism, in bacterial pathogens. In Gram-positive organisms, the σ54 is commonly associated with carbon metabolism. In this study, we show that the Enterococcus faecalis alternative sigma factor σ54 (RpoN) and its cognate enhancer binding protein MptR are essential for mannose utilization and are primary contributors to glucose uptake through the Mpt phosphotransferase system. To gain further insight into how RpoN contributes to global transcriptional changes, we performed microarray transcriptional analysis of strain V583 and an isogenic rpoN mutant grown in a chemically defined medium with glucose as the sole carbon source. Transcripts of 340 genes were differentially affected in the rpoN mutant; the predicted functions of these genes mainly related to nutrient acquisition. These differentially expressed genes included those with predicted catabolite-responsive element (cre) sites, consistent with loss of repression by the major carbon catabolite repressor CcpA. To determine if the inability to efficiently metabolize glucose/mannose affected infection outcome, we utilized two distinct infection models. We found that the rpoN mutant is significantly attenuated in both rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI). Here, we examined a ccpA mutant in the CAUTI model and showed that the absence of carbon catabolite control also significantly attenuates bacterial tissue burden in this model. Our data highlight the contribution of central carbon metabolism to growth of E. faecalis at various sites of infection.IMPORTANCE Hospital-acquired infections account for 2 billion dollars annually in increased health care expenses and cause more than 100,000 deaths in the United States alone. Enterococci are the second leading cause of hospital-acquired infections. They form biofilms at surgical sites and are often associated with infections of the urinary tract following catheterization. Nutrient uptake and growth are key factors that influence their ability to cause disease. Our research identified a large set of genes that illuminate nutrient uptake pathways in enterococci. Perturbation of the metabolic circuit reduces virulence in a rabbit endocarditis model, as well as in catheter-associated urinary tract infection in mice. Targeting metabolic pathways that are important in infection may lead to new treatments against multidrug-resistant enterococcal infections.},
	issn = {2150-7511},
	doi = {10.1128/mBio.00380-21},
	author = {Keffeler, Erica C and Iyer, Vijayalakshmi S and Parthasarathy, Srivatsan and Ramsey, Matthew M and Gorman, Matthew J and Barke, Theresa L and Varahan, Sriram and Olson, Sally and Gilmore, Michael S and Abdullahi, Zakria H and Hancock, Emmaleigh N and Hancock, Lynn E}
}
@article {1522734,
	title = {Convolutional Neural Networks Can Predict Retinal Differentiation in Retinal Organoids},
	journal = {Front Cell Neurosci},
	volume = {14},
	year = {2020},
	month = {2020},
	pages = {171},
	abstract = {We have developed a deep learning-based computer algorithm to recognize and predict retinal differentiation in stem cell-derived organoids based on bright-field imaging. The three-dimensional "organoid" approach for the differentiation of pluripotent stem cells (PSC) into retinal and other neural tissues has become a major strategy to recapitulate development. We decided to develop a universal, robust, and non-invasive method to assess retinal differentiation that would not require chemical probes or reporter gene expression. We hypothesized that basic-contrast bright-field (BF) images contain sufficient information on tissue specification, and it is possible to extract this data using convolutional neural networks (CNNs). Retina-specific Rx-green fluorescent protein mouse embryonic reporter stem cells have been used for all of the differentiation experiments in this work. The BF images of organoids have been taken on day 5 and fluorescent on day 9. To train the CNN, we utilized a transfer learning approach: ImageNet pre-trained ResNet50v2, VGG19, Xception, and DenseNet121 CNNs had been trained on labeled BF images of the organoids, divided into two categories (retina and non-retina), based on the fluorescent reporter gene expression. The best-performing classifier with ResNet50v2 architecture showed a receiver operating characteristic-area under the curve score of 0.91 on a test dataset. A comparison of the best-performing CNN with the human-based classifier showed that the CNN algorithm performs better than the expert in predicting organoid fate (84\% vs. 67 {\textpm} 6\% of correct predictions, respectively), confirming our original hypothesis. Overall, we have demonstrated that the computer algorithm can successfully recognize and predict retinal differentiation in organoids before the onset of reporter gene expression. This is the first demonstration of CNN{\textquoteright}s ability to classify stem cell-derived tissue .},
	issn = {1662-5102},
	doi = {10.3389/fncel.2020.00171},
	author = {Kegeles, Evgenii and Naumov, Anton and Karpulevich, Evgeny A and Volchkov, Pavel and Baranov, Petr}
}
@article {1559552,
	title = {Inpatient Virtual Vision Clinic Improves Access to Vision Rehabilitation Before and During the COVID-19 Pandemic},
	journal = {Arch Rehabil Res Clin Transl},
	volume = {3},
	number = {1},
	year = {2021},
	month = {2021 Mar},
	pages = {100100},
	abstract = {Objective: To describe and evaluate a secure video call system combined with a suite of iPad vision testing apps to improve access to vision rehabilitation assessment for inpatients. Design: Retrospective. Setting: Two acute care inpatient rehabilitation hospitals and 1 long-term acute care (LTAC) hospital. Participants: Records of inpatients seen by the vision service. Interventions: Records from a 1-year telemedicine pilot performed at acute rehabilitation (AR) hospital 1 and then expanded to AR hospital 2 and LTAC hospital during coronavirus disease 2019 (COVID-19) were reviewed. In the virtual visits, an occupational therapist measured the patients{\textquoteright} vision with the iPad applications and forwarded results to the off-site Doctor of Optometry (OD) for review prior to a video visit. The OD provided diagnosis and education, press-on prism application supervision, strategies and modifications, and follow-up recommendations. Providers completed the telehealth usability questionnaire (10-point scale). Main Outcome Measures: Vision examinations per month at AR hospital 1 before and with telemedicine. Results: With telemedicine at AR hospital 1, mean visits per month significantly increased from 10.7{\textpm}5 to 14.9{\textpm}5 (=.002). Prism was trialed in 40\% of cases of which 83\% were successful, similar to previously reported in-person success rates. COVID-19 caused only a marginal decrease in visits per month (=.08) at AR1, whereas the site without an established program (AR hospital 2) had a 3-4 week gap in care while the program was initiated. Cases at the LTAC hospital tended to be more complex and difficult to manage virtually. The telehealth usability questionnaire median category scores were 7 for , 8 for , 6 for , and 9 for . Conclusions: The virtual vision clinic process improved inpatient access to eye and visual neurorehabilitation assessment before and during the COVID-19 quarantine and was well accepted by providers and patients.},
	issn = {2590-1095},
	doi = {10.1016/j.arrct.2020.100100},
	author = {Keilty, Matthew and Houston, Kevin E and Collins, Caroline and Trehan, Ritika and Chen, Ya-Ting and Merabet, Lotfi and Watts, Amy and Pundlik, Shrinivas and Luo, Gang}
}
@article {382596,
	title = {Surgical management of strabismus in Duane retraction syndrome.},
	journal = {J AAPOS},
	volume = {19},
	number = {1},
	year = {2015},
	month = {2015 Feb},
	pages = {63-9},
	abstract = {SUMMARY: While Duane retraction syndrome (DRS) is relatively common, surgical management of the associated strabismus can be challenging because of the lack of abduction/adduction, the variable severity of muscle contracture, and the variety of clinical presentations. In this workshop a panel of experienced surgeons provide their perspective and practical tips on the management of strabismus in patients with DRS.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2014.10.019},
	author = {Kekunnaya, Ramesh and Kraft, Stephen and Rao, Venkateshwar B and Velez, Federico G and Sachdeva, Virender and Hunter, David G}
}
@article {1179136,
	title = {Removal of a barbed fish hook from the cornea of an 8-year-old boy},
	journal = {J AAPOS},
	year = {2017},
	month = {2017 Sep 13},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2017.06.023},
	author = {Kemp, Pavlina S and Shah, Ankoor S and Elliott, Alexandra T and Wan, Michael J}
}
@article {1333852,
	title = {Fluorometholone 0.1\% as Ancillary Therapy for Trachomatous Trichiasis Surgery: Randomized Clinical Trial},
	journal = {Am J Ophthalmol},
	volume = {197},
	year = {2019},
	month = {2019 Jan},
	pages = {145-155},
	abstract = {PURPOSE: To assess the hypothesis that fluorometholone 0.1\% eye drops are safe and effective as adjunctive therapy for trachomatous trichiasis (TT) surgery; determining the most promising dose. DESIGN: Randomized, placebo-controlled, double-masked parallel dose-ranging clinical trial. METHODS: Patients undergoing upper lid TT surgery at a rural Ethiopian hospital were randomized to fluorometholone 0.1\% twice daily for 4\&nbsp;weeks, 4 times daily for 4\&nbsp;weeks, 4 times daily for 8\&nbsp;weeks, or matching frequency placebo in a 3:1:3:1:3:1 ratio for 1 eye. Randomization was stratified by TT severity (1-4 vs >=5 lashes touching the globe). Safety outcomes (intraocular pressure [IOP] elevation, cataract, and other dose-limiting toxicities) and postoperative TT incidence were assessed over 1 year. RESULTS: Subjects randomized were 39:13:39:13:38:13 in the respective groups, and 1 subject in the 8-weeks fluorometholone group was withdrawn. Of 154 subjects, 148 (96.1\%) completed 1 year{\textquoteright}s follow-up. Among 76 eyes receiving fluorometholone 4 times daily, 1 developed IOP elevation >= 30\&nbsp;mm Hg (to 37\&nbsp;mm Hg) and 1 had an allergic reaction attributed to the study drug; each resolved upon drug cessation without sequelae. No cataract or other dose-limiting toxicity events occurred. Postoperative TT within 1 year occurred in 29.3\% of placebo eyes vs 17.7\%, 19.6\%, and 23.2\% among the respective fluorometholone groups (P\&nbsp;= .29 comparing placebo vs all active treatments combined). CONCLUSIONS: The results suggest fluorometholone 0.1\% is likely to be safe and efficacious to reduce postoperative TT following TT surgery, and 1 drop twice daily for 4\&nbsp;weeks is the most promising dose. Confirmation in a full-scale clinical trial is needed before programmatic implementation.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.09.017},
	author = {Kempen, John H and Tekle-Haimanot, Redda and Hunduma, Lelisa and Alemayehu, Menilik and Pistilli, Maxwell and Abashawl, Aida and Lawrence, Scott D and Alemayehu, Wondu}
}
@article {630226,
	title = {Remission of Intermediate Uveitis: Incidence and Predictive Factors.},
	journal = {Am J Ophthalmol},
	volume = {164},
	year = {2016},
	month = {2016 Apr},
	pages = {110-117.e2},
	abstract = {PURPOSE: To evaluate the incidence of remission among patients with intermediate uveitis; to identify factors potentially predictive of remission. DESIGN: Retrospective cohort study. METHODS: Involved eyes of patients with primary noninfectious intermediate uveitis at 4 academic ocular inflammation subspecialty practices, followed sufficiently long to meet the remission outcome definition, were studied retrospectively by standardized chart review data. Remission of intermediate uveitis was defined as a lack of inflammatory activity at >=2 visits spanning >=90\&nbsp;days in the absence of any corticosteroid or immunosuppressant medications. Factors potentially predictive of intermediate uveitis remission were evaluated using survival analysis. RESULTS: Among 849 eyes (of 510 patients) with intermediate uveitis followed over 1934 eye-years, the incidence of intermediate uveitis remission was 8.6/100 eye-years (95\% confidence interval [CI], 7.4-10.1). Factors predictive of disease remission included prior pars plana vitrectomy (PPV) (hazard ratio [HR] [vs no PPV]\&nbsp;= 2.39; 95\% CI, 1.42-4.00), diagnosis of intermediate uveitis within the last year (HR [vs diagnosis \&gt;5 years ago]\&nbsp;=3.82; 95\% CI, 1.91-7.63), age >=45 years (HR [vs age \&lt;45 years]\&nbsp;= 1.79; 95\% CI, 1.03-3.11), female sex (HR\&nbsp;= 1.61; 95\% CI, 1.04-2.49), and Hispanic race/ethnicity (HR [vs white race]\&nbsp;= 2.81; 95\% CI, 1.23-6.41). Presence/absence of a systemic inflammatory disease, laterality of uveitis, and smoking status were not associated with differential incidence. CONCLUSIONS: Our results suggest that intermediate uveitis is a chronic disease with an overall low rate of remission. Recently diagnosed patients and older, female, and Hispanic patients were more likely to remit. With regard to management, pars plana vitrectomy was associated with increased probability of remission.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.12.034},
	author = {Kempen, John H and Gewaily, Dina Y and Newcomb, Craig W and Liesegang, Teresa L and Ka{\c c}maz, R Oktay and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Foster, C Stephen and Jabs, Douglas A and Payal, Abhishek and Fitzgerald, Tonetta D and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Research Group}
}
@article {1732586,
	title = {Use of Immunosuppression and the Risk of Subsequent Overall or Cancer Mortality},
	journal = {Ophthalmology},
	volume = {130},
	number = {12},
	year = {2023},
	month = {2023 Dec},
	pages = {1258-1268},
	abstract = {PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR]\&nbsp;= 0.95, 95\% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR\&nbsp;= 1.04, 95\% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR]\&nbsp;= 0.88, 0.89, 0.90, 1.11) and CM (aHR\&nbsp;= 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Adalimumab, Alkylating Agents, Antimetabolites, Azathioprine, Calcineurin Inhibitors, Cohort Studies, Cyclosporine, Humans, Immunosuppression Therapy, Immunosuppressive Agents, Infliximab, Methotrexate, Mycophenolic Acid, Neoplasms, Retrospective Studies, Tumor Necrosis Factor Inhibitors},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.07.023},
	author = {Kempen, John H and Newcomb, Craig W and Washington, Terri L and Foster, C Stephen and Sobrin, Lucia and Thorne, Jennifer E and Jabs, Douglas A and Suhler, Eric B and Rosenbaum, James T and Sen, H Nida and Levy-Clarke, Grace A and Nussenblatt, Robert B and Bhatt, Nirali P and Lowder, Careen Y and Goldstein, Debra A and Leiderman, Yannek I and Acharya, Nisha R and Holland, Gary N and Read, Russell W and Dunn, James P and Dreger, Kurt A and Artornsombudh, Pichaporn and Begum, Hosne A and Fitzgerald, Tonetta D and Kothari, Srishti and Payal, Abhishek R and Daniel, Ebenezer and Gangaputra, Sapna S and Ka{\c c}maz, R Oktay and Liesegang, Teresa L and Pujari, Siddharth S and Khachatryan, Naira and Maghsoudlou, Armin and Suga, Hilkiah K and Pak, Clara M and Helzlsouer, Kathy J and Buchanich, Jeanine M and Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Research Group}
}
@article {1522732,
	title = {Incidence and Outcome of Uveitic Glaucoma in Eyes With Intermediate, Posterior, or Panuveitis Followed up to 10 Years After Randomization to Fluocinolone Acetonide Implant or Systemic Therapy},
	journal = {Am J Ophthalmol},
	volume = {219},
	year = {2020},
	month = {2020 11},
	pages = {303-316},
	abstract = {PURPOSE: To evaluate long-term risk and outcomes of glaucoma in eyes with intermediate, posterior, and panuveitis managed with systemic or fluocinolone acetonide (0.59\&nbsp;mg, "implant") therapy. DESIGN: Prospective Follow-up of the Multicenter Uveitis Steroid Treatment (MUST) Clinical Trial Cohort. METHODS: Patients with intermediate, posterior, or panuveitis randomized to implant or systemic therapy (corticosteroid plus immunosuppression in \&gt;90\%) were followed prospectively for glaucoma incidence and outcome. RESULTS: Among 405 uveitic at-risk eyes of 232 patients (median follow-up\&nbsp;= 6.9 years), 40\% (79/196) of eyes assigned and treated with implant and 8\% (17/209) of eyes assigned and treated with systemic therapy (censoring eyes receiving an implant on implantation) developed glaucoma (hazard ratio [HR]\&nbsp;= 5.9, 95\% confidence interval [CI] 3.2, 10.8; P \&lt; .001). Adjustment for intraocular pressure (IOP) elevation during follow-up only partially mitigated the association of implant treatment with glaucoma incidence: HR\&nbsp;= 3.1 (95\% CI 1.6, 6.0); P\&nbsp;= .001. Among 112 eyes of 83 patients developing glaucoma, the 5-year cumulative incidence following diagnosis of sustained (2 or more consecutive visits) worsening of mean deviation by >=6 dB was 20\% (95\% CI 12\%, 33\%); 5-year cumulative incidence of sustained worsening of cup-to-disc ratio by >=0.2 was 26\% (95\% CI 17\%, 39\%). CONCLUSIONS: The implant has substantially higher risk of glaucoma than systemic therapy, a difference not entirely explained by posttreatment IOP elevation. Management of IOP elevation was effective in preventing worsening of glaucoma for the large majority of cases, but even under expert clinical management, some glaucoma worsened. Uveitis cases should be monitored carefully for IOP elevation and glaucoma indefinitely.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.06.038},
	author = {Kempen, John H and Van Natta, Mark L and Friedman, David S and Altaweel, Michael M and Ansari, Husam and Dunn, James P and Elner, Susan G and Holbrook, Janet T and Lim, Lyndell L and Sugar, Elizabeth A and Jabs, Douglas A and Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group}
}
@article {1435405,
	title = {Remission of Non-Infectious Anterior Scleritis: Incidence and Predictive Factors},
	journal = {Am J Ophthalmol},
	volume = {223},
	year = {2021},
	month = {2021 Mar},
	pages = {377-395},
	abstract = {PURPOSE: To assess how often non-infectious anterior scleritis remits and identify predictive factors. METHODS: Our retrospective cohort study at four ocular inflammation subspecialty centers collected data for each affected eye/patient at every visit from center inception (1978, 1978, 1984, 2005) until 2010. Remission was defined as inactivity of disease off all suppressive medications at all visits spanning at least three consecutive months or at all visits up to the last visit (to avoid censoring patients stopping follow-up after remission). Factors potentially predictive of remission were assessed using Cox regression models. RESULTS: During 1,906 years{\textquoteright} aggregate follow-up of 832 affected eyes, remission occurred in 214 (170 of 584 patients). Median time-to-remission of scleritis\&nbsp;= 7.8 years (95\% confidence interval [CI]: 5.7, 9.5). More remissions occurred earlier than later during follow-up. Factors predictive of less scleritis remission included scleritis bilaterality (adjusted hazard ratio [aHR]\&nbsp;= 0.46, 95\% CI: 0.32-0.65); and diagnosis with any systemic inflammatory disease (aHR\&nbsp;= 0.36, 95\% CI: 0.23-0.58), or specifically with Rheumatoid Arthritis (aHR\&nbsp;= 0.22), or Granulomatosis with Polyangiitis (aHR\&nbsp;= 0.08). Statin treatment (aHR\&nbsp;= 1.53, 95\% CI: 1.03-2.26) within <=90\&nbsp;days was associated with more remission incidence. CONCLUSIONS: Our results suggest scleritis remission occurs more slowly in anterior scleritis than in newly diagnosed anterior uveitis or chronic anterior uveitis, suggesting that attempts at tapering suppressive medications is warranted after long intervals of suppression. Remission is less frequently achieved when systemic inflammatory diseases are present. Confirmatory studies of whether adjunctive statin treatment truly can enhance scleritis remission (as suggested here) are needed.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.03.024},
	author = {Kempen, John H and Pistilli, Maxwell and Begum, Hosne and Fitzgerald, Tonetta D and Liesegang, Teresa L and Payal, Abhishek and Zebardast, Nazlee and Bhatt, Nirali P and Foster, C Stephen and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study Research Group}
}
@article {1532381,
	title = {SARS-CoV-2 Serosurvey in Addis Ababa, Ethiopia},
	journal = {Am J Trop Med Hyg},
	volume = {103},
	number = {5},
	year = {2020},
	month = {2020 11},
	pages = {2022-2023},
	abstract = {In a serosurvey of asymptomatic people from the general population recruited from a clinical laboratory in May 2020 in Addis Ababa, Ethiopia, three of 99 persons tested positive for SARS-CoV-2 IgG (3.0\%, 95\% binomial exact confidence interval: 0.6-8.6\%). Taking into account pretest probability and the sampling scheme, the range of plausible population prevalence values was approximately 1.0-8.4\%. These results suggest that a larger number of people have been infected than the counts detected by surveillance to date; nevertheless, the results suggest the large majority of the general population in Addis Ababa currently is susceptible to COVID-19.},
	keywords = {Adult, Betacoronavirus, Coronavirus Infections, Ethiopia, Female, Humans, Male, Pandemics, Pneumonia, Viral, Population Surveillance, Prevalence, Seroepidemiologic Studies},
	issn = {1476-1645},
	doi = {10.4269/ajtmh.20-0816},
	author = {Kempen, John H and Abashawl, Aida and Suga, Hilkiah K and Nigussie Difabachew, Mesfin and Kempen, Christopher J and Tesfaye Debele, Melaku and Menkir, Abel A and Assefa, Maranatha T and Asfaw, Eyob H and Habtegabriel, Leul B and Sitotaw Addisie, Yohannes and Nilles, Eric J and Longenecker, Joseph C}
}
@article {1658679,
	title = {Two fine-scale channels for encoding motion and stereopsis within the human magnocellular stream},
	journal = {Prog Neurobiol},
	volume = {220},
	year = {2023},
	month = {2023 Jan},
	pages = {102374},
	abstract = {In humans and non-human primates (NHPs), motion and stereopsis are processed within fine-scale cortical sites, including V2 thick stripes and their extensions into areas V3 and V3A that are believed to be under the influence of magnocellular stream. However, in both species, the relative functional organization (overlapping vs. none overlapping) of these sites remains unclear. Using high-resolution functional MRI (fMRI), we found evidence for two minimally-overlapping channels within human extrastriate areas that contribute to processing motion and stereopsis. Across multiple experiments that included different stimuli (random dots, gratings, and natural scenes), the functional selectivity of these channels for motion vs. stereopsis remained consistent. Furthermore, an analysis of resting-state functional connectivity revealed stronger functional connectivity within the two channels rather than between them. This finding provides a new perspective toward the mesoscale organization of the magnocellular stream within the human extrastriate visual cortex, beyond our previous understanding based on animal models.},
	keywords = {Animals, Brain Mapping, Depth Perception, Humans, Magnetic Resonance Imaging, Rivers, Visual Cortex, Visual Pathways},
	issn = {1873-5118},
	doi = {10.1016/j.pneurobio.2022.102374},
	author = {Kennedy, B and Bex, P. and Hunter, D.G. and Nasr, S}
}
@article {1623375,
	title = {Comment on "Cornea Classic Article: Kim JC and Tseng SCG: Transplantation of Preserved Amniotic Membrane for Surface Reconstruction in Severely Damaged Rabbit Corneas (Cornea 1995;14:473-484)"},
	journal = {Cornea},
	volume = {41},
	number = {2},
	year = {2022},
	month = {2022 Feb 01},
	pages = {135-136},
	abstract = {ABSTRACT: Following identification of limbal stem cells, efforts have been devoted to restore and/or replace these essential progenitors of the corneal epithelium. Limbal stem cell deficiency, commonly a consequence of ocular chemical injury, results in clinically compromised vision consequent to corneal conjunctivalization. The insight of Kim and Tseng provided experimental proof of the concept that even in the presence of total limbal stem cell deficiency, amnion membrane overlay grafts can promote limbal recovery as a means of ocular surface reconstruction.},
	keywords = {Amnion, Animals, Cornea, Corneal Diseases, Epithelium, Corneal, Rabbits, Stem Cell Transplantation},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002647},
	author = {Kenyon, Kenneth R}
}
@article {1297785,
	title = {Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase},
	journal = {J Am Chem Soc},
	volume = {140},
	number = {5},
	year = {2018},
	month = {2018 Feb 07},
	pages = {1774-1782},
	abstract = {Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.},
	issn = {1520-5126},
	doi = {10.1021/jacs.7b11212},
	author = {Keohane, Colleen E and Steele, Andrew D and Fetzer, Christian and Khowsathit, Jittasak and Van Tyne, Daria and Moyni{\'e}, Lucile and Gilmore, Michael S and Karanicolas, John and Sieber, Stephan A and Wuest, William M}
}
@article {1698246,
	title = {The Treatment of Acute Optic Neuritis},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {6},
	year = {2023},
	month = {2023 Aug},
	pages = {511-514},
	abstract = {Despite the high incidence of optic neuritis (ON), and the growing number of therapeutic options for the long-term treatment of diseases associated with ON including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody associated disease (MOGAD), there are still only limited therapeutic options for treating an acute event of optic neuritis. These include steroids, plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). High-dose steroids remain the mainstay of acute treatment. However, evidence is emerging that when optic neuritis is accompanied with certain atypical features that suggest a more unfavorable outcome this mandates special consideration such as early addition of other therapeutic agents or tapering the steroid very slowly. This review will distinguish between typical and atypical neuritis and discuss acute treatment options.},
	keywords = {Autoantibodies, Humans, Multiple Sclerosis, Myelin-Oligodendrocyte Glycoprotein, Neuromyelitis Optica, Optic Neuritis},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2211662},
	author = {Keyhanian, Kiandokht and Chwalisz, Bart K}
}
@article {1109831,
	title = {Identification of Padi2 as a novel angiogenesis-regulating gene by genome association studies in mice},
	journal = {PLoS Genet},
	volume = {13},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {e1006848},
	abstract = {Recent findings indicate that growth factor-driven angiogenesis is markedly influenced by genetic variation. This variation in angiogenic responsiveness may alter the susceptibility to a number of angiogenesis-dependent diseases. Here, we utilized the genetic diversity available in common inbred mouse strains to identify the loci and candidate genes responsible for differences in angiogenic response. The corneal micropocket neovascularization assay was performed on 42 different inbred mouse strains using basic fibroblast growth factor (bFGF) pellets. We performed a genome-wide association study utilizing efficient mixed-model association (EMMA) mapping using the induced vessel area from all strains. Our analysis yielded five loci with genome-wide significance on chromosomes 4, 8, 11, 15 and 16. We further refined the mapping on chromosome 4 within a haplotype block containing multiple candidate genes. These genes were evaluated by expression analysis in corneas of various inbred strains and in vitro functional assays in human microvascular endothelial cells (HMVECs). Of these, we found the expression of peptidyl arginine deiminase type II (Padi2), known to be involved in metabolic pathways, to have a strong correlation with a haplotype shared by multiple high angiogenic strains. In addition, inhibition of Padi2 demonstrated a dosage-dependent effect in HMVECs. To investigate its role in vivo, we knocked down Padi2 in transgenic kdrl:zsGreen zebrafish embryos using morpholinos. These embryos had disrupted vessel formation compared to control siblings. The impaired vascular pattern was partially rescued by human PADI2 mRNA, providing evidence for the specificity of the morphant phenotype. Taken together, our study is the first to indicate the potential role of Padi2 as an angiogenesis-regulating gene. The characterization of Padi2 and other genes in associated pathways may provide new understanding of angiogenesis regulation and novel targets for diagnosis and treatment of a wide variety of angiogenesis-dependent diseases.},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1006848},
	author = {Khajavi, Mehrdad and Zhou, Yi and Birsner, Amy E and Bazinet, Lauren and Rosa Di Sant, Amanda and Schiffer, Alex J and Rogers, Michael S and Krishnaji, Subrahmanian Tarakkad and Hu, Bella and Nguyen, Vy and Zon, Leonard and D{\textquoteright}Amato, Robert J}
}
@article {1593867,
	title = {Identification of Basp1 as a novel angiogenesis-regulating gene by multi-model system studies},
	journal = {FASEB J},
	volume = {35},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {e21404},
	abstract = {We have previously used the genetic diversity available in common inbred mouse strains to identify quantitative trait loci (QTLs) responsible for the differences in angiogenic response using the corneal micropocket neovascularization (CoNV) assay. Employing a mouse genome-wide association study (GWAS) approach, the region on chromosome 15 containing Basp1 was identified as being significantly associated with angiogenesis in inbred strains. Here, we developed a unique strategy to determine and verify the role of BASP1 in angiogenic pathways. Basp1 expression in cornea had a strong correlation with a haplotype shared by mouse strains with varied angiogenic phenotypes. In addition, inhibition of BASP1 demonstrated a dosage-dependent effect in both primary mouse brain endothelial and human microvascular endothelial cell (HMVEC) migration. To investigate its role in vivo, we knocked out basp1 in transgenic kdrl:zsGreen zebrafish embryos using a widely adopted CRISPR-Cas9 system. These embryos had severely disrupted vessel formation compared to control siblings. We further show that basp1 promotes angiogenesis by upregulating β-catenin gene and the Dll4/Notch1 signaling pathway. These results, to the best of our knowledge, provide the first in vivo evidence to indicate the role of Basp1 as an angiogenesis-regulating gene and opens the potential therapeutic avenues for a wide variety of systemic angiogenesis-dependent diseases.},
	issn = {1530-6860},
	doi = {10.1096/fj.202001936RRR},
	author = {Khajavi, Mehrdad and Zhou, Yi and Schiffer, Alex J and Bazinet, Lauren and Birsner, Amy E and Zon, Leonard and D{\textquoteright}Amato, Robert J}
}
@article {1528414,
	title = {Ciprofloxacin-loaded bioadhesive hydrogels for ocular applications},
	journal = {Biomater Sci},
	volume = {8},
	number = {18},
	year = {2020},
	month = {2020 Sep 15},
	pages = {5196-5209},
	abstract = {The management of corneal infections often requires complex therapeutic regimens involving the prolonged and high-frequency application of antibiotics that provide many challenges to patients and impact compliance with the therapeutic regimens. In the context of severe injuries that lead to tissue defects (e.g. corneal lacerations) topical drug regimens are inadequate and suturing is often indicated. There is thus an unmet need for interventions that can provide tissue closure while concurrently preventing or treating infection. In this study, we describe the development of an antibacterial bioadhesive hydrogel loaded with micelles containing ciprofloxacin (CPX) for the management of corneal injuries at risk of infection. The in vitro release profile showed that the hydrogel system can release CPX, a broad-spectrum antibacterial drug, for up to 24 h. Moreover, the developed CPX-loaded hydrogels exhibited excellent antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa, two bacterial strains responsible for the most ocular infections. Physical characterization, as well as adhesion and cytocompatibility tests, were performed to assess the effect of CPX loading in the developed hydrogel. Results showed that CPX loading did not affect stiffness, adhesive properties, or cytocompatibility of hydrogels. The efficiency of the antibacterial hydrogel was assessed using an ex vivo model of infectious pig corneal injury. Corneal tissues treated with the antibacterial hydrogel showed a significant decrease in bacterial colony-forming units (CFU) and a higher corneal epithelial viability after 24 h as compared to non-treated corneas and corneas treated with hydrogel without CPX. These results suggest that the developed adhesive hydrogel system presents a promising suture-free solution to seal corneal wounds while preventing infection.},
	issn = {2047-4849},
	doi = {10.1039/d0bm00935k},
	author = {Khalil, Islam A and Saleh, Bahram and Ibrahim, Dina M and Jumelle, Clotilde and Yung, Ann and Dana, Reza and Annabi, Nasim}
}
@article {742266,
	title = {Retinal Dysfunction in Patients with Congenital Fibrosis of the Extraocular Muscles Type 2.},
	journal = {Ophthalmic Genet},
	volume = {37},
	number = {2},
	year = {2016},
	month = {2016 Jun},
	pages = {130-6},
	abstract = {INTRODUCTION: Congenital fibrosis of the extraocular muscles type 2 (CFEOM2) is a distinct non-syndromic form of congenital incomitant strabismus secondary to orbital dysinnervation from recessive mutations in the gene PHOX2A. The phenotype includes bilateral ptosis, very large angle exotropia, ophthalmoplegia, and poorly-reactive pupils. Other than amblyopia, afferent visual dysfunction has not been considered part of CFEOM2; however, we have repeatedly observed non-amblyopic subnormal vision in affected patients. The purpose of this study was to document this recurrent feature of the phenotype. METHODS: A retrospective case series (2002-2012). RESULTS: Eighteen patients (four families) were identified; all affected individuals had confirmed homozygous recessive PHOX2A mutations except one individual for whom genetic testing was not done because of multiple genetically confirmed family members. Age at assessment ranged from 5-62 years old (median 10 years old). All patients had decreased best-corrected visual acuity not completely explainable by amblyopia in both the preferred and non-preferred eye. In those patients who had further ancillary testing, visual fields (five patients) and electroretinography (10 patients) confirmed abnormalities not ascribable to amblyopia. CONCLUSIONS: In addition to a distinct form of congenital incomitant strabismus, the phenotype of CFEOM2 includes subnormal vision consistent with retinal dysfunction. This could be the direct result of PHOX2A mutations or a secondary effect of orbital dysinnervation.},
	issn = {1744-5094},
	doi = {10.3109/13816810.2014.926942},
	author = {Khan, Arif O and Almutlaq, Mohammed and Oystreck, Darren T and Engle, Elizabeth C and Abu-Amero, Khaled and Bosley, Thomas}
}
@article {1363131,
	title = {Ocular mucosal CD11b+ and CD103+ mouse dendritic cells under normal conditions and in allergic immune responses},
	journal = {PLoS One},
	volume = {8},
	number = {5},
	year = {2013},
	month = {2013},
	pages = {e64193},
	abstract = {Steady state dendritic cells (DC) found in non-lymphoid tissue sites under normal physiologic conditions play a pivotal role in triggering T cell responses upon immune provocation. CD11b+ and CD103+ DC have received considerable attention in this regard. However, still unknown is whether such CD11b+ and CD103+ DC even exist in the ocular mucosa, and if so, what functions they have in shaping immune responses. We herein identified in the ocular mucosa of normal wild-type (WT) and Flt3-/- mice the presence of a CD11b+ DC (i.e., CD11c+ MHCII+ CD11b+ CD103- F4/80+ Sirp-a+). CD103+ DC (i.e. CD11c+ MHCII+ CD11b low CD103+ CD8a+ DEC205+ Langerin+) were also present in WT, but not in Flt3-/- mice. These CD103+ DC expressed high levels of Id2 and Flt3 mRNA; whereas CD11b+ DC expressed high Irf4, Csfr, and Cx3cr1 mRNA. Additionally, the functions of these DC differed in response to allergic immune provocation. This was assessed utilizing a previously validated model, which includes transferring specific populations of exogenous DC into the ocular mucosa of ovalbumin (OVA)/alum-primed mice. Interestingly, in such mice, topical OVA instillation following engraftment of exogenous CD11b+ DC led to dominant allergic T cell responses and clinical signs of ocular allergy relative to those engrafted with CD103+ DC. Thus, although CD11b+ and CD103+ DC are both present in the normal ocular mucosa, the CD11b+ DC subset plays a dominant role in a mouse model of ocular allergy.},
	keywords = {Adaptive Immunity, Animals, Antigens, CD, CD11b Antigen, Dendritic Cells, Eye, Female, fms-Like Tyrosine Kinase 3, Gene Knockout Techniques, Hypersensitivity, Integrin alpha Chains, Mice, Mice, Inbred C57BL, Mucous Membrane, Phenotype, Transcription, Genetic},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0064193},
	author = {Khandelwal, Payal and Blanco-Mezquita, Tomas and Emami, Parisa and Lee, Hyun Soo and Reyes, Nancy J and Mathew, Rose and Huang, Randy and Saban, Daniel R}
}
@article {1364624,
	title = {Androgen regulation of gene expression in human meibomian gland and conjunctival epithelial cells},
	journal = {Mol Vis},
	volume = {18},
	year = {2012},
	month = {2012},
	pages = {1055-67},
	abstract = {PURPOSE: Androgens exert a significant influence on the structure, function and/or pathophysiology of the meibomian gland and conjunctiva. We sought to determine whether this hormone action involves the regulation of epithelial cell gene expression in these tissues. METHODS: Immortalized human meibomian gland and conjunctival epithelial cells were treated with placebo or dihydrotestosterone (DHT) and processed for molecular biologic procedures. Gene expression was evaluated with BeadChips and data were analyzed with bioinformatic and statistical software. RESULTS: Androgen treatment significantly influenced the expression of approximately 3,000 genes in immortalized human meibomian gland and conjunctival epithelial cells. The nature of DHT action on gene activity was predominantly cell-specific. Similarly, DHT exerted a significant, but primarily cell-specific, influence on many gene ontologies and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These included groups of genes related, for example, to lipid dynamics, innate immunity, cell cycle, Janus kinase (JAK)-signal transducer and activator of transcription (stat) cascades, oxidative phosphorylation, the proteasome, and mammalian target of rapamycin (mTOR), Wnt, and peroxisome proliferator-activated receptor (PPAR) signaling. CONCLUSIONS: Our findings support our hypothesis that androgens regulate gene expression in human meibomian gland and conjunctival epithelial cells. Our ongoing studies are designed to determine whether many of these genes are translated and play a role in the health and well being of the eye.},
	keywords = {Androgens, Cell Line, Transformed, Conjunctiva, Dihydrotestosterone, Epithelial Cells, Gene Expression Profiling, Gene Expression Regulation, Humans, Meibomian Glands, Oligonucleotide Array Sequence Analysis, Organ Specificity, Real-Time Polymerase Chain Reaction},
	issn = {1090-0535},
	author = {Khandelwal, Payal and Liu, Shaohui and Sullivan, David A}
}
@article {1435406,
	title = {Longitudinal Clinical Follow-up and Genetic Spectrum of Patients With Rod-Cone Dystrophy Associated With Mutations in PDE6A and PDE6B},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Apr 18},
	abstract = {Importance: A precise phenotypic characterization of retinal dystrophies is needed for disease modeling as a basis for future therapeutic interventions. Objective: To compare genotype, phenotype, and structural changes in patients with rod-cone dystrophy (RCD) associated with mutations in PDE6A or PDE6B. Design, Setting, and Participants: In a retrospective cohort study conducted in Paris, France, from January 2007 to September 2017, 54 patients from a cohort of 1095 index patients with RCD underwent clinical examination, including personal and familial history, best-corrected visual acuity (BCVA), color vision, slitlamp examination, full-field electroretinography, kinetic visual fields (VFs), retinophotography, optical coherence tomography, near-infrared fundus autofluorescence, and short-wavelength fundus autofluorescence imaging. Genotyping was performed using microarray analysis, targeted next-generation sequencing, and Sanger sequencing validation with familial segregation when possible. Data were analyzed from September 1, 2017, to February 1, 2018. Clinical variables were subsequently analyzed in 2018. Main Outcomes and Measures: Phenotype and genotype comparison of patients carrying mutations in PDE6A or PDE6B. Results: Of the 54 patients included in the study, 19 patients of 17 families (11 women [58\%]; mean [SD] age at diagnosis, 14.83 [10.63] years) carried pathogenic mutations in PDE6A, and 35 patients of 26 families (17 women [49\%]; mean [SD] age at diagnosis, 21.10 [11.56] years) had mutations in PDE6B, accounting for prevalences of 1.6\% and 2.4\%, respectively. Among 49 identified genetic variants, 14 in PDE6A and 15 in PDE6B were novel. Overall, phenotypic analysis revealed no substantial differences between the 2 groups except for night blindness as a presenting symptom that was noted to be more prevalent in the PDE6A than PDE6B group (80\% vs 37\%, respectively; P = .005). The mean binocular BCVA and VF decrease over time (measured as mean individual slopes coefficients) was comparable between patients with PDE6A and PDE6B mutations: 0.04 (0.12) vs 0.02 (0.05) for BCVA (P = .89) and 14.33 (7.12) vs 13.27 (6.77) for VF (P = .48). Conclusions and Relevance: Mutations in PDE6A and PDE6B accounted for 1.6\% and 2.4\%, respectively, in a cohort of French patients with RCD. The functional and structural findings reported may constitute the basis of disease modeling that might be used for better prognostic estimation and candidate selection for photoreceptor therapeutic rescue.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.6367},
	author = {Khateb, Samer and Nassisi, Marco and Bujakowska, Kinga M and M{\'e}j{\'e}case, C{\'e}cile and Condroyer, Christel and Antonio, Aline and Foussard, Marine and D{\'e}montant, Vanessa and Mohand-Sa{\"\i}d, Saddek and Sahel, Jos{\'e}-Alain and Zeitz, Christina and Audo, Isabelle}
}
@article {1318866,
	title = {Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma},
	journal = {Nat Genet},
	volume = {50},
	number = {6},
	year = {2018},
	month = {2018 Jun},
	pages = {778-782},
	abstract = {Glaucoma is the leading cause of irreversible blindness globally . Despite its gravity, the disease is frequently undiagnosed in the community . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG). Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.},
	issn = {1546-1718},
	doi = {10.1038/s41588-018-0126-8},
	author = {Khawaja, Anthony P and Cooke Bailey, Jessica N and Wareham, Nicholas J and Scott, Robert A and Simcoe, Mark and Igo, Robert P and Song, Yeunjoo E and Wojciechowski, Robert and Cheng, Ching-Yu and Khaw, Peng T and Pasquale, Louis R and Haines, Jonathan L and Foster, Paul J and Wiggs, Janey L and Hammond, Chris J and Hysi, Pirro G and UK Biobank Eye and Vision Consortium and NEIGHBORHOOD Consortium}
}
@article {913486,
	title = {Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {11},
	year = {2016},
	month = {2016 Sep 1},
	pages = {5046-5052},
	abstract = {Purpose: Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. Methods: We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. Results: We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P \&lt; 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010). Conclusions: We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20017},
	author = {Khawaja, Anthony P and Cooke Bailey, Jessica N and Kang, Jae Hee and Allingham, R Rand and Hauser, Michael A and Brilliant, Murray and Budenz, Donald L and Christen, William G and Fingert, John and Gaasterland, Douglas and Gaasterland, Terry and Kraft, Peter and Lee, Richard K and Lichter, Paul R and Liu, Yutao and Medeiros, Felipe and Moroi, Syoko E and Richards, Julia E and Realini, Tony and Ritch, Robert and Schuman, Joel S and Scott, William K and Singh, Kuldev and Sit, Arthur J and Vollrath, Douglas and Wollstein, Gadi and Zack, Donald J and Zhang, Kang and Pericak-Vance, Margaret and Weinreb, Robert N and Haines, Jonathan L and Pasquale, Louis R and Wiggs, Janey L}
}
@article {1078756,
	title = {Patients{\textquoteright} Perceived Treatment Effectiveness in Dry Eye Disease},
	journal = {Cornea},
	volume = {36},
	number = {8},
	year = {2017},
	month = {2017 Aug},
	pages = {893-897},
	abstract = {PURPOSE: Patients{\textquoteright} perceptions of the effectiveness of a treatment, or perceived treatment effectiveness (PTE), play an important role in medicine. This study aimed to evaluate patients{\textquoteright} PTE in dry eye disease (DED) and investigate factors contributing to these patients{\textquoteright} perceptions. METHODS: This cross-sectional study included 66 patients with DED. At enrollment, all patients had comprehensive ophthalmic assessment. In addition, to evaluate the patient{\textquoteright}s PTE, they were asked to use a 10-point scale ranging from "strongly disagree (score 1)" to "strongly agree (score 10)" to score their views on whether their DED treatments had been effective. Changes in clinical parameters of DED over time during their care were also evaluated retrospectively and correlated with the patients{\textquoteright} PTE. RESULTS: The mean age of patients was 55.7 years; 79\% were women. Regarding patients{\textquoteright} PTE, 36.4\% strongly (score 10) and 53.0\% moderately (scores 6-9) believed that their DED treatment had been effective. However, 10.6\% thought that their treatment had not been effective (scores 1-5). Less favorable PTE for the DED treatment was significantly associated with a younger age (P \&lt; 0.001), current use of antidepressant medications (P = 0.01), and a higher Ocular Surface Disease Index score (P = 0.01) at enrollment. CONCLUSIONS: A majority of patients with DED have positive perceptions regarding the effectiveness of their treatments. Less favorable perceptions are associated with more severe ocular symptoms and nonocular parameters such as younger age and current antidepressant use. In DED management, assessing patients{\textquoteright} PTE should be considered as an important part of clinical practice.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001216},
	author = {Kheirkhah, Ahmad and Crnej, Alja and Ren, Ai and Mullins, Andrew and Satitpitakul, Vannarut and Hamrah, Pedram and Schaumberg, Debra and Dana, Reza}
}
@article {397826,
	title = {Reduced Corneal Endothelial Cell Density inPatients With Dry Eye Disease.},
	journal = {Am J Ophthalmol},
	volume = {159},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {1022-1026.e2},
	abstract = {PURPOSE: To evaluate corneal endothelial cell density (ECD) in patients with dry eye disease (DED) compared to an age-matched control group. DESIGN: Cross-sectional, controlled study. METHODS: This study included 90 eyes of 45 patients with moderate to severe DED (aged 53.7 {\textpm} 9.8 years) and 30 eyes of 15 normal controls (aged 50.7 {\textpm} 9.8 years). All subjects had a complete ophthalmic evaluation including symptom assessment using the Ocular Surface Disease Index (OSDI) and corneal fluorescein staining. In addition, laser scanning in\&nbsp;vivo confocal microscopy was performed to measure the density of the following parameters in the central cornea: endothelial cells, subbasal nerves, and subbasal immune dendritic cells. RESULTS: Corneal ECD was significantly lower in the DED group (2595.8 {\textpm} 356.1 cells/mm(2)) than in the control group (2812.7 {\textpm} 395.2 cells/mm(2), P\&nbsp;= .046). The DED group showed significantly lower corneal subbasal nerve density (17.1 {\textpm} 6.9\&nbsp;mm/mm(2)) compared to the control group (24.7 {\textpm} 4.4\&nbsp;mm/mm(2), P \&lt; .001). Dendritic cell density was significantly higher in the DED group than in the controls (111.7 {\textpm} 137.3 vs 32.0 {\textpm} 24.4 cells/mm(2), respectively, P\&nbsp;= .002). There were statistically significant correlations between corneal ECD and dry eye severity parameters including the OSDI score (rs\&nbsp;=\&nbsp;-0.26, P\&nbsp;= .03), and corneal fluorescein staining (rs\&nbsp;=\&nbsp;-0.28, P\&nbsp;= .008). CONCLUSIONS: There is a significant reduction in corneal ECD in DED that correlates with clinical severity of the disease.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.03.011},
	author = {Kheirkhah, Ahmad and Saboo, Ujwala S and Abud, Tulio B and Dohlman, Thomas H and Arnoldner, Michael A and Hamrah, Pedram and Dana, Reza}
}
@article {959426,
	title = {Patients With Dry Eye Disease and Low Subbasal Nerve Density Are at High Risk for Accelerated Corneal Endothelial Cell Loss.},
	journal = {Cornea},
	year = {2016},
	month = {2016 Nov 02},
	abstract = {PURPOSE: To evaluate changes in corneal endothelial cell density over time in patients with dry eye disease (DED) and to correlate endothelial cell loss with corneal subbasal nerve density. METHODS: This retrospective study included 40 eyes of 20 patients with DED. Laser in vivo confocal microscopy had been performed in the central cornea of both eyes at an initial visit and repeated after a mean follow-up of 33.2 {\textpm} 10.2 months. The densities of corneal endothelial cells and subbasal nerves were measured in both visits and compared with 13 eyes of 13 normal age-matched controls. RESULTS: At the initial visit, the DED group had lower densities of corneal endothelial cells (2620 {\textpm} 386 cells/mm) and subbasal nerves (17.8 {\textpm} 7.5 mm/mm) compared with the control group (2861 {\textpm} 292 cells/mm and 22.8 {\textpm} 3.0 mm/mm, with P = 0.08 and P = 0.01, respectively). At the end of follow-up, although there was no significant change in subbasal nerve density (16.7 {\textpm} 7.2 mm/mm, P = 0.43), the mean corneal endothelial cell density significantly decreased to 2465 {\textpm} 391 cells/mm (P = 0.01), with a mean corneal endothelial cell loss of 2.1 {\textpm} 3.6\% per year. The endothelial cell loss showed a statistically significant negative correlation with the initial subbasal nerve density (Rs = -0.55, P = 0.02). CONCLUSIONS: Patients with DED have an accelerated corneal endothelial cell loss compared with that reported in the literature for normal aging. Those with lower subbasal nerve density, in particular, are at a higher risk for endothelial cell loss over time.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001057},
	author = {Kheirkhah, Ahmad and Satitpitakul, Vannarut and Hamrah, Pedram and Dana, Reza}
}
@article {1016076,
	title = {Patients With Dry Eye Disease and Low Subbasal Nerve Density Are at High Risk for Accelerated Corneal Endothelial Cell Loss},
	journal = {Cornea},
	volume = {36},
	number = {2},
	year = {2017},
	month = {2017 Feb},
	pages = {196-201},
	abstract = {PURPOSE: To evaluate changes in corneal endothelial cell density over time in patients with dry eye disease (DED) and to correlate endothelial cell loss with corneal subbasal nerve density.

METHODS: This retrospective study included 40 eyes of 20 patients with DED. Laser in vivo confocal microscopy had been performed in the central cornea of both eyes at an initial visit and repeated after a mean follow-up of 33.2 {\textpm} 10.2 months. The densities of corneal endothelial cells and subbasal nerves were measured in both visits and compared with 13 eyes of 13 normal age-matched controls.

RESULTS: At the initial visit, the DED group had lower densities of corneal endothelial cells (2620 {\textpm} 386 cells/mm) and subbasal nerves (17.8 {\textpm} 7.5 mm/mm) compared with the control group (2861 {\textpm} 292 cells/mm and 22.8 {\textpm} 3.0 mm/mm, with P = 0.08 and P = 0.01, respectively). At the end of follow-up, although there was no significant change in subbasal nerve density (16.7 {\textpm} 7.2 mm/mm, P = 0.43), the mean corneal endothelial cell density significantly decreased to 2465 {\textpm} 391 cells/mm (P = 0.01), with a mean corneal endothelial cell loss of 2.1 {\textpm} 3.6\% per year. The endothelial cell loss showed a statistically significant negative correlation with the initial subbasal nerve density (Rs = -0.55, P = 0.02).

CONCLUSIONS: Patients with DED have an accelerated corneal endothelial cell loss compared with that reported in the literature for normal aging. Those with lower subbasal nerve density, in particular, are at a higher risk for endothelial cell loss over time.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001057},
	author = {Kheirkhah, Ahmad and Satitpitakul, Vannarut and Hamrah, Pedram and Dana, Reza}
}
@article {1125336,
	title = {Sensitivity and Specificity of Laser-Scanning In Vivo Confocal Microscopy for Filamentous Fungal Keratitis: Role of Observer Experience},
	journal = {Am J Ophthalmol},
	volume = {179},
	year = {2017},
	month = {2017 Jul},
	pages = {81-89},
	abstract = {PURPOSE: To determine sensitivity and specificity of laser-scanning in\&nbsp;vivo confocal microscopy (LS-IVCM) for detection of filamentous fungi in patients with microbial keratitis and to evaluate the effect of observer{\textquoteright}s imaging experience on these parameters. DESIGN: Retrospective reliability study. METHODS: This study included 21 patients with filamentous fungal keratitis and 24 patients with bacterial keratitis (as controls). The etiology of infection was confirmed based on the response to specific therapy regardless of culture results. All patients had undergone full-thickness corneal imaging by a LS-IVCM (Heidelberg Retina Tomograph 3 with Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany). The images were evaluated for the presence of fungal filaments by 2 experienced observers and 2 inexperienced observers. All observers were masked to the clinical and microbiologic data. RESULTS: The mean number of images obtained per eye was 917 {\textpm} 353. The average sensitivity of LS-IVCM for detecting fungal filaments was 71.4\% {\textpm} 0\% for the experienced observers and 42.9\% {\textpm} 6.7\% for the inexperienced observers. The average specificity was 89.6\% {\textpm} 3.0\% and 87.5\% {\textpm} 17.7\% for these 2 groups of observers, respectively. Although there was a good agreement between the 2 experienced observers (κ\&nbsp;= 0.77), the inexperienced observers showed only a moderate interobserver agreement (κ\&nbsp;= 0.51). The LS-IVCM sensitivity was higher in patients with fungal infections who had positive culture or longer duration of the disease. CONCLUSIONS: Although LS-IVCM has a high specificity for diagnosing filamentous fungal keratitis, its sensitivity is moderate and highly dependent on the level of the\&nbsp;observer{\textquoteright}s experience and training with this imaging\&nbsp;modality.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Cornea, Eye Infections, Fungal, Female, Humans, Keratitis, Male, Microscopy, Confocal, Middle Aged, Reproducibility of Results, Retrospective Studies, ROC Curve, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.04.011},
	author = {Kheirkhah, Ahmad and Syed, Zeba A and Satitpitakul, Vannarut and Goyal, Sunali and M{\"u}ller, Rodrigo and Tu, Elmer Y and Dana, Reza}
}
@article {591241,
	title = {Corneal Epithelial Immune Dendritic Cell Alterations in Subtypes of Dry Eye Disease: A Pilot In Vivo Confocal Microscopic Study.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {12},
	year = {2015},
	month = {2015 Nov 1},
	pages = {7179-85},
	abstract = {PURPOSE: To evaluate density and morphology of corneal epithelial immune dendritic cells (DCs) in different subtypes of dry eye disease (DED) using in vivo confocal microscopy (IVCM). METHODS: This retrospective study included 59 eyes of 37 patients with DED and 40 eyes of 20 age-matched healthy controls. Based on clinical tests, eyes with DED were categorized into two subtypes: aqueous-deficient (n = 35) and evaporative (n = 24). For all subjects, images of laser scanning in vivo confocal microscopy (IVCM) of the central cornea were analyzed for DC density and DC morphology (DC size, number of dendrites, and DC field). These DC parameters were compared among all dry eye and control groups. RESULTS: Compared with the controls, patients with DED had significantly higher DC density, larger DC size, higher number of dendrites, and larger DC field (all P \&lt; 0.001). Comparison between aqueous-deficient and evaporative subtypes demonstrated that DC density was significantly higher in aqueous-deficient subtype (189.8 {\textpm} 36.9 vs. 58.9 {\textpm} 9.4 cells/mm2, P = 0.001). However, there were no significant differences in morphologic parameters between DED subtypes. When aqueous-deficient DED with underlying systemic immune disease (Sj{\"o}gren{\textquoteright}s syndrome and graft versus host disease) were compared with nonimmune conditions, the immunologic subgroup showed significantly higher DC density, DC size, and number of dendrites (all P \&lt; 0.05). CONCLUSIONS: Corneal IVCM demonstrated differential changes in DC density and morphologic DC parameters between subtypes of DED. These changes, which reflect the degree of immune activation and inflammation in DED, can be used for clinical practice and endpoints in clinical trials.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17433},
	author = {Kheirkhah, Ahmad and Rahimi Darabad, Raheleh and Cruzat, Andrea and Hajrasouliha, Amir Reza and Witkin, Deborah and Wong, Nadia and Dana, Reza and Hamrah, Pedram}
}
@article {603916,
	title = {Overestimation of Corneal Endothelial Cell Density in Smaller Frame Sizes in In Vivo Confocal Microscopy.},
	journal = {Cornea},
	volume = {35},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {363-9},
	abstract = {PURPOSE: To evaluate the effect of frame size on the calculated corneal endothelial cell density (CECD) in images of laser scanning in vivo confocal microscopy (IVCM). METHODS: Forty-nine corneal endothelial images acquired by laser scanning IVCM (Heidelberg Retina Tomograph 3 with Rostock Corneal Module) with different endothelial cell densities were analyzed. In each image (160,000 μm), the CECD was calculated using the fixed-frame method by counting cells in the following frame sizes: 80,000 μm, 40,000 μm, 20,000 μm, 10,000 μm, 5000 μm, and 2500 μm. The calculated CECD was then compared with that of the variable-frame method as the reference value. RESULTS: There was no significant difference in the calculated CECD between the variable-frame method (2004 {\textpm} 832 cells/mm), and the fixed-frame method using a 40,000-μm frame (2023 {\textpm} 810 cells/mm). On the other hand, the calculated CECD showed significant overestimations in frame sizes of 20,000 μm (2066 {\textpm} 820 cells/mm), 10,000 μm (2156 {\textpm} 785 cells/mm), 5000 μm (2352 {\textpm} 783 cells/mm), and 2500 μm (2715 {\textpm} 754 cells/mm), with P \&lt; 0.001 in all. This resulted in overestimations of 4.8 {\textpm} 9.8\%, 11.9 {\textpm} 16.2\%, 24.9 {\textpm} 23.1\%, and 49.1 {\textpm} 38.8\% for these frame sizes, respectively. Images with lower CECD demonstrated higher overestimations of cell density in smaller frame sizes. CONCLUSIONS: In laser scanning IVCM images, there is significant overestimation of CECD if the cells are counted in frames smaller than 25\% of the image. Similar frame sizes should be used when monitoring CECD over time.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000698},
	author = {Kheirkhah, Ahmad and Saboo, Ujwala S and Marmalidou, Anna and Dana, Reza}
}
@article {1304383,
	title = {Subtarsal Fibrosis Is Associated With Ocular Surface Epitheliopathy in Graft-Versus-Host Disease},
	journal = {Am J Ophthalmol},
	volume = {189},
	year = {2018},
	month = {2018 May},
	pages = {102-110},
	abstract = {PURPOSE: To evaluate occurrence of subtarsal fibrosis in patients with graft-vs-host disease (GVHD) and to determine its association with ocular surface epitheliopathy.

DESIGN: Cross-sectional study.

METHODS: We enrolled 40 patients with moderate or severe dry eye disease, including 20 patients with chronic ocular GVHD and 20 patients without (as the control group). All patients had a comprehensive ophthalmic assessment including evaluation for subtarsal fibrosis, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer test. Furthermore, meibomian gland drop-out area and densities of epithelial and stromal immune cells were measured using meibography and in~vivo confocal microscopy, respectively.

RESULTS: Subtarsal fibrosis was not seen in any eye of the non-GVHD group. However, 16 eyes (40\%) of 10 patients (50\%) in the GVHD group had subtarsal fibrosis (P < .001) with an average involvement of 28.9\% {\textpm} 13.7\% of the tarsal area. Fibrosis was more frequent in the upper lids (35\%) than in the lower lids (5\%). Regression analyses showed that corneal fluorescein staining was significantly associated with the extent of fibrosis (P < .001, β~= 0.14) and TBUT (P < .001, β~=~-0.53) but not with other clinical or imaging parameters. Conjunctival lissamine green staining also had a statistically significant association with the extent of fibrosis (P~= .04, β~= 0.12) but not other clinical or imaging parameters. Eyes with subtarsal fibrosis had a more severe ocular surface epitheliopathy compared with eyes without fibrosis.

CONCLUSIONS: Subtarsal fibrosis is present in a significant percentage of patients with chronic ocular GVHD, likely contributing to the ocular surface damage in these patients.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.02.020},
	author = {Kheirkhah, Ahmad and Coco, Giulia and Satitpitakul, Vannarut and Dana, Reza}
}
@article {1452958,
	title = {Limbal and Conjunctival Epithelial Thickness in Ocular Graft-Versus-Host Disease},
	journal = {Cornea},
	volume = {38},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {1286-1290},
	abstract = {PURPOSE: To compare the thickness of the limbal epithelium (LE) and the bulbar conjunctival epithelium (BCE) between patients with dry eye disease (DED) with and without ocular graft-versus-host disease (GVHD). METHODS: This cross-sectional study enrolled 40 patients with moderate to severe DED including 20 with and 20 without chronic ocular GVHD. All patients had a comprehensive clinical ophthalmic assessment. Moreover, the thickness of the LE and BCE in both nasal and temporal regions of both eyes was measured using spectral domain optical coherence tomography. RESULTS: The average LE thickness in all patients with dry eye (GVHD and non-GVHD) was 65.8 {\textpm} 11.9 μm temporally and 69.7 {\textpm} 11.1 μm nasally (P = 0.02). The average BCE thickness was 55.8 {\textpm} 11.4 μm temporally and 60.1 {\textpm} 11.0 μm nasally (P = 0.03). There were no statistically significant differences between GVHD and non-GVHD groups in LE thickness (69.6 {\textpm} 11.7 vs. 66.1 {\textpm} 6.2 μm, respectively, P = 0.31) or BCE thickness (58.9 {\textpm} 9.6 vs. 57.3 {\textpm} 9.8 μm, respectively, P = 0.82). There was a significant correlation between LE thickness and BCE thickness (P = 0.01, Rs = 0.41). A statistically significant negative correlation was also observed between LE thickness and age (P = 0.002, Rs = -0.35). There were no significant correlations between the thickness of the LE or BCE and other clinical parameters. CONCLUSIONS: No difference exists in the thickness of the ocular surface epithelia between dry eyes with and without ocular GVHD, which would suggest that these epithelial changes may be independent of the underlying etiology and possibly only reflect the disease severity. Furthermore, there are regional variations in the thickness of the ocular surface epithelia in patients with DED.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002066},
	author = {Kheirkhah, Ahmad and Coco, Giulia and Satitpitakul, Vannarut and Pham, Tommy T and Dana, Reza}
}
@article {341636,
	title = {Effects of corneal nerve density on the response to treatment in dry eye disease.},
	journal = {Ophthalmology},
	volume = {122},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {662-8},
	abstract = {PURPOSE: To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment. DESIGN: Phase IV, double-masked, randomized clinical trial. PARTICIPANTS: Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls. METHODS: Patients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5\%, or loteprednol etabonate 0.5\%/tobramycin 0.3\% twice daily for 4 weeks. At baseline, in\&nbsp;vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups: those with low baseline SNFL and those with near-normal baseline SNFL for this purpose (the cutoff point: the mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups. MAIN OUTCOME MEASURES: Symptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer{\textquoteright}s test, and SNFL. RESULTS: In patients with DED, baseline SNFL (17.06{\textpm}5.78 mm/mm(2)) was significantly lower than in controls (23.68{\textpm}3.42 mm/mm(2), P\&nbsp;= 0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (\&lt;16.84 mm/mm(2)), subjects with near-normal baseline SNFL (>=16.84 mm/mm(2)) showed significant improvement in both symptoms and CFS score (all P \&lt; 0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL. CONCLUSIONS: Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may assist in explaining the variability of patients{\textquoteright} response to DED therapy.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.11.006},
	author = {Kheirkhah, Ahmad and Dohlman, Thomas H and Amparo, Francisco and Arnoldner, Michael A and Jamali, Arsia and Hamrah, Pedram and Dana, Reza}
}
@article {1062826,
	title = {A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-Associated Ocular Surface Disease},
	journal = {Cornea},
	volume = {36},
	number = {7},
	year = {2017},
	month = {2017 Jul},
	pages = {799-804},
	abstract = {PURPOSE: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical functions in T-cell activation and in inflammation. Because of their antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This pilot study was designed to assess the safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic solution for treatment of ocular surface disease in graft-versus-host disease (GVHD). METHODS: This phase 2, double-masked, randomized, pilot trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive topical 0.5\% R348, 0.2\% R348, or vehicle, twice daily for 12 weeks. Before and after treatment, a comprehensive ophthalmic evaluation was performed, which included Ocular Surface Disease Index (OSDI) questionnaire, Ocular Comfort Index questionnaire, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test with anesthesia. Changes in these parameters were compared between the 3 groups. RESULTS: The mean decrease in total corneal fluorescein staining at 12 weeks after treatment was higher in the 0.5\% R348 group (-6.0 {\textpm} 3.9, NEI scoring) compared with the vehicle (-2.1 {\textpm} 2.6, P = 0.045) or the 0.2\% R348 group (-4.1 {\textpm} 3.6, P = 0.34). However, there were no significant differences among the groups in terms of treatment-induced changes in OSDI, Ocular Comfort Index, conjunctival lissamine green staining, or Schirmer scores. R348 eye drops were well tolerated. CONCLUSIONS: This pilot study indicates that 0.5\% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated and may have some therapeutic efficacy in treating ocular GVHD. Larger trials are required to derive more definitive data.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001206},
	author = {Kheirkhah, Ahmad and Di Zazzo, Antonio and Satitpitakul, Vannarut and Fernandez, Merle and Magilavy, Daniel and Dana, Reza}
}
@article {541266,
	title = {Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {10},
	year = {2015},
	month = {2015 Sep 1},
	pages = {5801-7},
	abstract = {PURPOSE: To evaluate whether the densities of corneal subbasal nerves and epithelial immune dendritiform cells (DCs) are comparable between a set of three representative standard images of in vivo confocal microscopy (IVCM) and the wide-field mapped composite IVCM images. METHODS: This prospective, cross-sectional, and masked study included 110 eyes of 58 patients seen in a neurology clinic who underwent laser-scanning IVCM (Heidelberg Retina Tomograph 3) of the central cornea. Densities of subbasal corneal nerves and DCs were compared between the average of three representative standard images and the wide-field mapped composite images, which were reconstructed by automated mapping. RESULTS: There were no statistically significant differences between the average of three representative standard images (0.16 mm2 each) and the wide-field composite images (1.29 {\textpm} 0.64 mm2) in terms of mean subbasal nerve density (17.10 {\textpm} 6.10 vs. 17.17 {\textpm} 5.60 mm/mm2, respectively, P = 0.87) and mean subbasal DC density (53.2 {\textpm} 67.8 vs. 49.0 {\textpm} 54.3 cells/mm2, respectively, P = 0.43). However, there were notable differences in subbasal nerve and DC densities between these two methods in eyes with very low nerve density or very high DC density. CONCLUSIONS: There are no significant differences in the mean subbasal nerve and DC densities between the average values of three representative standard IVCM images and wide-field mapped composite images. Therefore, these standard images can be used in clinical studies to accurately measure cellular structures in the subbasal layer.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17434},
	author = {Kheirkhah, Ahmad and Muller, Rodrigo and Mikolajczak, Janine and Ren, Ai and Kadas, Ella Maria and Zimmermann, Hanna and Pruess, Harald and Paul, Friedemann and Brandt, Alexander U and Hamrah, Pedram}
}
@article {1295868,
	title = {Factors Influencing the Diagnostic Accuracy of Laser-Scanning In Vivo Confocal Microscopy for Acanthamoeba Keratitis},
	journal = {Cornea},
	volume = {37},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {818-823},
	abstract = {PURPOSE: To determine the factors that influence the sensitivity and specificity of laser-scanning in vivo confocal microscopy (IVCM) for diagnosing Acanthamoeba keratitis (AK). METHODS: This retrospective, controlled study included 28 eyes of 27 patients with AK and 34 eyes of 34 patients with bacterial keratitis (as the control group). All patients had undergone corneal imaging with a laser-scanning IVCM (Heidelberg Retina Tomograph 3 with the Rostock Cornea Module). The IVCM images were independently evaluated by 2 experienced and 2 inexperienced masked observers. Sensitivity and specificity of IVCM for diagnosing AK and the effects of various clinical and imaging parameters on the sensitivity were then investigated. RESULTS: Overall, IVCM had average sensitivity and specificity of 69.7\% {\textpm} 2.5\% and 97.1\% {\textpm} 4.2\% for experienced observers and 59.0\% {\textpm} 7.6\% and 92.7\% {\textpm} 10.4\% for inexperienced observers, respectively. However, the sensitivity did not show any significant association with the duration of disease, size of ulcer, depth of involvement, culture results, or cyst morphology. Although interobserver agreement was good (κ = 0.60, P \&lt; 0.001) for the experienced observers, it was only at a moderate level (κ = 0.48, P \&lt; 0.001) for the inexperienced observers. CONCLUSIONS: IVCM has a moderate sensitivity and a high specificity for diagnosis of AK. Although clinical parameters do not affect this diagnostic accuracy, a higher sensitivity is seen when images are interpreted by experienced observers.},
	keywords = {Acanthamoeba Keratitis, Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Corneal Ulcer, Female, Humans, Male, Microscopy, Confocal, Middle Aged, Sensitivity and Specificity, Young Adult},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001507},
	author = {Kheirkhah, Ahmad and Satitpitakul, Vannarut and Syed, Zeba A and M{\"u}ller, Rodrigo and Goyal, Sunali and Tu, Elmer Y and Dana, Reza}
}
@article {1445343,
	title = {Three-Dimensional Optical Coherence Tomography Imaging For Glaucoma Associated With Boston Keratoprosthesis Type I and II},
	journal = {J Glaucoma},
	volume = {28},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {718-726},
	abstract = {PRECIS: Three-dimensional (3D) spectral domain optical coherence tomography (OCT) volume scans of the optic nerve head (ONH) and the peripapillary area are useful in the management of glaucoma in patients with a type I or II Boston Keratoprosthesis (KPro). PURPOSE: The purpose of this study was to report the use of spectral domain OCT in the management of glaucoma in patients with a type I or II Boston KPro. MATERIALS AND METHODS: This study is an observational case series. Four consecutive patients with KPro implants were referred for glaucoma evaluation. A comprehensive eye examination was performed which included disc photography, visual field testing, and high-density spectral domain OCT volume scans of the ONH and the peripapillary area. 2D and 3D parameters were calculated using custom-designed segmentation algorithms developed for glaucoma management. RESULTS: Spectral domain OCT parameters provided useful information in the diagnosis and management of 4 KPro patients. OCT parameters which can be used in KPro patients included 2D retinal nerve fiber layer (RNFL) thickness, 3D peripapillary RNFL volume, 3D peripapillary retinal thickness and volume, 3D cup volume, and 3D neuroretinal rim thickness and volume. In 3 of 4 cases where the traditional 2D RNFL thickness scan was limited by artifacts, 3D spectral domain OCT volume scans provided useful quantitative objective measurements of the ONH and peripapillary region. Therefore, 3D parameters derived from high-density volume scans as well as radial scans of the ONH can be used to overcome the limitations and artifacts associated with 2D RNFL thickness scans. CONCLUSIONS: Spectral domain OCT volume scans offer the possibility to enhance the evaluation of KPro patients with glaucoma by using both 2D and 3D diagnostic parameters that are easily obtained in a clinic setting.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001280},
	author = {Khoueir, Ziad and Jassim, Firas and Braaf, Boy and Poon, Linda Yi-Chieh and Tsikata, Edem and Chodosh, James and Dohlman, Claes H and Vakoc, Benjamin J and Bouma, Brett E and de Boer, Johannes F and Chen, Teresa C}
}
@article {1195256,
	title = {Diagnostic Capability of Peripapillary Three-dimensional Retinal Nerve Fiber Layer Volume for Glaucoma Using Optical Coherence Tomography Volume Scans},
	journal = {Am J Ophthalmol},
	volume = {182},
	year = {2017},
	month = {2017 Oct},
	pages = {180-193},
	abstract = {PURPOSE: To determine the diagnostic capability of peripapillary 3-dimensional (3D) retinal nerve fiber layer (RNFL) volume measurements from spectral-domain optical coherence tomography (OCT) volume scans for open-angle glaucoma (OAG). DESIGN: Assessment of diagnostic accuracy. METHODS: Setting: Academic clinical setting. STUDY POPULATION: Total of 180 patients (113 OAG and 67 normal subjects). OBSERVATION PROCEDURES: One eye per subject was included. Peripapillary 3D RNFL volumes were calculated for global, quadrant, and sector regions, using 4 different-size annuli. Peripapillary 2D RNFL thickness circle scans were also obtained. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios. RESULTS: Among all 2D and 3D RNFL parameters, best diagnostic capability was associated with inferior quadrant 3D RNFL volume of the smallest annulus (AUROC value 0.977). Otherwise, global 3D RNFL volume AUROC values were comparable to global 2D RNFL thickness AUROC values for all 4 annulus sizes (P values: .0593 to .6866). When comparing the 4 annulus sizes for global RNFL volume, the smallest annulus had the best AUROC values (P values: .0317 to .0380). The smallest-size annulus may have the best diagnostic potential, partly owing to having no areas excluded for being larger than the 6\&nbsp;{\texttimes}\&nbsp;6\&nbsp;mm(2) scanned region. CONCLUSION: Peripapillary 3D RNFL volume showed excellent diagnostic performance for detecting glaucoma. Peripapillary 3D RNFL volume parameters have the same or better diagnostic capability compared to peripapillary 2D RNFL thickness measurements, although differences were not statistically significant.},
	keywords = {Aged, Area Under Curve, Cross-Sectional Studies, False Negative Reactions, Female, Glaucoma, Open-Angle, Humans, Imaging, Three-Dimensional, Intraocular Pressure, Male, Middle Aged, Nerve Fibers, Optic Disk, Predictive Value of Tests, Reproducibility of Results, Retinal Ganglion Cells, ROC Curve, Sensitivity and Specificity, Tomography, Optical Coherence, Visual Field Tests, Visual Fields},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.08.001},
	author = {Khoueir, Ziad and Jassim, Firas and Poon, Linda Yi-Chieh and Tsikata, Edem and Ben-David, Geulah S and Liu, Yingna and Shieh, Eric and Lee, Ramon and Guo, Rong and Papadogeorgou, Georgia and Braaf, Boy and Simavli, Huseyin and Que, Christian and Vakoc, Benjamin J and Bouma, Brett E and de Boer, Johannes F and Chen, Teresa C}
}
@article {1354360,
	title = {Prevalence estimates of substandard drugs in Mongolia using a random sample survey},
	journal = {Springerplus},
	volume = {3},
	year = {2014},
	month = {2014},
	pages = {709},
	abstract = {To determine the prevalence of substandard drugs in urban (Ulaanbaatar) and rural (selected provinces) areas of Mongolia, samples of 9 common, therapeutically important drugs were collected from randomly selected drug outlets in Ulaanbaatar and 4 rural provinces by "mystery shoppers". Samples were analyzed by visual inspection, registration status, and biochemical analysis. Samples failing to meet all Pharmacopeia quality tests were considered substandard. In the rural provinces, 69 out of 388 samples were substandard, giving an estimated prevalence of substandard drugs of 17.8\% (95\% CI: 14.1-22.0). There were 85 unregistered samples, giving a prevalence estimate of unregistered drugs of 21.9\%. (95\% CI: 17.9-26.3). In the urban Ulaanbaatar districts, 112 out of 848 samples were substandard, giving an estimated prevalence of substandard drugs of 13.2\% (95\% CI: 11.0-15.7). There were 150 unregistered samples, giving a prevalence estimate of unregistered drugs of 17.7\% (95\% CI: 15.2-20.4). In the rural provinces, 35 out of 85 (41.2\%) unregistered samples were substandard; whereas 34 out of 303 (11.2\%) registered samples were substandard. (p \&lt; 0.0001) In the urban districts, 18 out of 150 (12.0\%) unregistered samples were substandard, whereas 94 out of 698 registered were substandard. (13.5\%) (p = 0.6). The prevalence of substandard and unregistered drugs is higher in rural provinces. There is a significant association between substandard and unregistered drugs in the provinces but not in the urban districts. The underlying causes for substandard drugs need to be further investigated in order to help formulate strategies to improve pharmacovigilance and the drug supply quality in Mongolia.},
	issn = {2193-1801},
	doi = {10.1186/2193-1801-3-709},
	author = {Khurelbat, Daariimaa and Dorj, Gereltuya and Bayarsaikhan, Enkhtuul and Chimedsuren, Munkhdelger and Sanjjav, Tsetsegmaa and Morimoto, Takeshi and Morley, Michael and Morley, Katharine}
}
@article {1782281,
	title = {Overlap between ophthalmology and psychiatry - A narrative review focused on congenital and inherited conditions},
	journal = {Psychiatry Res},
	volume = {331},
	year = {2024},
	month = {2024 Jan},
	pages = {115629},
	abstract = {A number of congenital and inherited diseases present with both ocular and psychiatric features. The genetic inheritance and phenotypic variants play a key role in disease severity. Early recognition of the signs and symptoms of those disorders is critical to earlier intervention and improved prognosis. Typically, the associations between these two medical subspecialties of ophthalmology and psychiatry are poorly understood by most practitioners so we hope to provide a narrative review to improve the identification and management of these disorders. We conducted a comprehensive review of the literature detailing the diseases with ophthalmic and psychiatric overlap that were more widely represented in the literature. Herein, we describe the clinical features, pathophysiology, molecular biology, diagnostic tests, and the most recent approaches for the treatment of these diseases. Recent studies have combined technologies for ocular and brain imaging such as optical coherence tomography (OCT) and functional imaging with genetic testing to identify the genetic basis for eye-brain connections. Additional work is needed to further explore these potential biomarkers. Overall, accurate, efficient, widely distributed and non-invasive tests that can help with early recognition of these diseases will improve the management of these patients using a multidisciplinary approach.},
	keywords = {Genetic Testing, Humans, Ophthalmology, Psychiatry},
	issn = {1872-7123},
	doi = {10.1016/j.psychres.2023.115629},
	author = {Kiely, Chelsea and Douglas, Konstantinos Aa and Douglas, Vivian Paraskevi and Miller, John B and Lizano, Paulo}
}
@article {369091,
	title = {Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers.},
	journal = {Cold Spring Harb Perspect Biol},
	volume = {7},
	number = {1},
	year = {2015},
	month = {2015 Jan},
	pages = {a018622},
	abstract = {Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription. Emerging studies, showing that eRNAs function in controlling mRNA transcription, challenge the idea that enhancers are merely sites of transcription factor assembly. Instead, communication between promoters and enhancers can be bidirectional with promoters required to activate enhancer transcription. Reciprocally, eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription.},
	issn = {1943-0264},
	doi = {10.1101/cshperspect.a018622},
	author = {Kim, Tae-Kyung and Hemberg, Martin and Gray, Jesse M}
}
@article {1363132,
	title = {X-linked juvenile retinoschisis (XLRS): a review of genotype-phenotype relationships},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {392-6},
	abstract = {X-linked juvenile retinoschisis (XLRS) is one of the most common genetic causes of juvenile progressive retinal-vitreal degeneration in males. To date, more than 196 different mutations of the RS1 gene have been associated with XLRS. The mutation spectrum is large and the phenotype variable. This review will focus on the clinical features of XLRS and examine the relationship between phenotype and genotype.},
	keywords = {Eye Proteins, Genetic Association Studies, Humans, Mutation, Retinoschisis},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825299},
	author = {Kim, David Y and Mukai, Shizuo}
}
@article {1364625,
	title = {A brief history of anti-VEGF for the treatment of ocular angiogenesis},
	journal = {Am J Pathol},
	volume = {181},
	number = {2},
	year = {2012},
	month = {2012 Aug},
	pages = {376-9},
	abstract = {In 1994, The American Journal of Pathology published a key article reporting that hypoxic retina produces vascular endothelial growth factor (VEGF), suggesting a role for VEGF in ocular neovascularization. Subsequent developments in anti-VEGF treatment for neovascular eye disease have improved visual outcomes and changed the standard of care in retinal medicine and ophthalmology.},
	keywords = {Angiogenesis Inhibitors, Animals, Eye, History, 20th Century, History, 21st Century, Humans, Neovascularization, Pathologic, Vascular Endothelial Growth Factor A},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2012.06.006},
	author = {Kim, Leo A and D{\textquoteright}Amore, Patricia A}
}
@article {1309972,
	title = {A new class of synthetic retinoid antibiotics effective against bacterial persisters},
	journal = {Nature},
	volume = {556},
	number = {7699},
	year = {2018},
	month = {2018 04 05},
	pages = {103-107},
	abstract = {A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant {\textquoteright}persister{\textquoteright} subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.},
	issn = {1476-4687},
	doi = {10.1038/nature26157},
	author = {Kim, Wooseong and Zhu, Wenpeng and Hendricks, Gabriel Lambert and Van Tyne, Daria and Steele, Andrew D and Keohane, Colleen E and Fricke, Nico and Conery, Annie L and Shen, Steven and Pan, Wen and Lee, Kiho and Rajamuthiah, Rajmohan and Fuchs, Beth Burgwyn and Vlahovska, Petia M and Wuest, William M and Gilmore, Michael S and Gao, Huajian and Ausubel, Frederick M and Mylonakis, Eleftherios}
}
@article {836906,
	title = {Revisiting the mouse model of oxygen-induced retinopathy.},
	journal = {Eye Brain},
	volume = {8},
	year = {2016},
	month = {2016},
	pages = {67-79},
	abstract = {Abnormal blood vessel growth in the retina is a hallmark of many retinal diseases, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy, and the wet form of age-related macular degeneration. In particular, ROP has been an important health concern for physicians since the advent of routine supplemental oxygen therapy for premature neonates more than 70 years ago. Since then, researchers have explored several animal models to better understand ROP and retinal vascular development. Of these models, the mouse model of oxygen-induced retinopathy (OIR) has become the most widely used, and has played a pivotal role in our understanding of retinal angiogenesis and ocular immunology, as well as in the development of groundbreaking therapeutics such as anti-vascular endothelial growth factor injections for wet age-related macular degeneration. Numerous refinements to the model have been made since its inception in the 1950s, and technological advancements have expanded the use of the model across multiple scientific fields. In this review, we explore the historical developments that have led to the mouse OIR model utilized today, essential concepts of OIR, limitations of the model, and a representative selection of key findings from OIR, with particular emphasis on current research progress.},
	issn = {1179-2744},
	doi = {10.2147/EB.S94447},
	author = {Kim, Clifford B and D{\textquoteright}Amore, Patricia A and Connor, Kip M}
}
@article {1233386,
	title = {Development of the Visual Word Form Area Requires Visual Experience: Evidence from Blind Braille Readers},
	journal = {J Neurosci},
	volume = {37},
	number = {47},
	year = {2017},
	month = {2017 Nov 22},
	pages = {11495-11504},
	abstract = {Learning to read causes the development of a letter- and word-selective region known as the visual word form area (VWFA) within the human ventral visual object stream. Why does a reading-selective region develop at this anatomical location? According to one hypothesis, the VWFA develops at the nexus of visual inputs from retinotopic cortices and linguistic input from the frontotemporal language network because reading involves extracting linguistic information from visual symbols. Surprisingly, the anatomical location of the VWFA is also active when blind individuals read Braille by touch, suggesting that vision is not required for the development of the VWFA. In this study, we tested the alternative prediction that VWFA development is in fact influenced by visual experience. We predicted that in the absence of vision, the "VWFA" is incorporated into the frontotemporal language network and participates in high-level language processing. Congenitally blind (n = 10, 9 female, 1 male) and sighted control (n = 15, 9 female, 6 male), male and female participants each took part in two functional magnetic resonance imaging experiments: (1) word reading (Braille for blind and print for sighted participants), and (2) listening to spoken sentences of different grammatical complexity (both groups). We find that in blind, but not sighted participants, the anatomical location of the VWFA responds both to written words and to the grammatical complexity of spoken sentences. This suggests that in blindness, this region takes on high-level linguistic functions, becoming less selective for reading. More generally, the current findings suggest that experience during development has a major effect on functional specialization in the human cortex.SIGNIFICANCE STATEMENT The visual word form area (VWFA) is a region in the human cortex that becomes specialized for the recognition of written letters and words. Why does this particular brain region become specialized for reading? We tested the hypothesis that the VWFA develops within the ventral visual stream because reading involves extracting linguistic information from visual symbols. Consistent with this hypothesis, we find that in congenitally blind Braille readers, but not sighted readers of print, the VWFA region is active during grammatical processing of spoken sentences. These results suggest that visual experience contributes to VWFA specialization, and that different neural implementations of reading are possible.},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.0997-17.2017},
	author = {Kim, Judy S and Kanjlia, Shipra and Merabet, Lotfi B and Bedny, Marina}
}
@article {1528405,
	title = {The Search for Antifungal Prophylaxis After Artificial Corneal Surgery-An In Vitro Study},
	journal = {Cornea},
	volume = {39},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {1547-1555},
	abstract = {PURPOSE: To evaluate the antifungal properties of topical antibiotics (already being used successfully to prevent bacterial endophthalmitis) and some promising antiseptics for antifungal prophylaxis in the setting of artificial corneal implantation. METHODS: Several commonly used antibiotics for antimicrobial prophylaxis after artificial corneal implantation, in addition to antiseptics [benzalkonium chloride (BAK), povidone-iodine (PI), and some ionic liquids (ILs)], were tested in vitro against Candida albicans, Fusarium solani, and Aspergillus fumigatus. The time-kill activity was determined. Toxicity was assayed in vitro on human corneal epithelial cultures using trypan blue. Adhesion and tissue invasion experiments were also carried out on porcine corneas and commonly used contact lenses, with or without gamma irradiation, and by analysis with fluorescence microscopy. RESULTS: Polymyxin B (PMB)/trimethoprim/BAK (Polytrim), PMB alone, gatifloxacin with BAK (Zymaxid), and same-concentration BAK alone exhibited antifungal activity in vitro. Moxifloxacin (MOX) or gatifloxacin without BAK-as well as trimethoprim, vancomycin, and chloramphenicol-had no effect. 1\% PI and ILs had the highest efficacy/toxicity ratios (\&gt;1), and Polytrim was species dependent. Subfungicidal concentrations of Polytrim reduced adhesion of C. albicans to Kontur contact lenses. Gamma-irradiated corneas showed enhanced resistance to fungal invasion. CONCLUSIONS: Of antibiotic preparations already in use for bacterial prophylaxis after KPro surgery, Polytrim is a commonly used antibiotic with antifungal effects mediated by both PMB and BAK and may be sufficient for prophylaxis. PI as a 1\% solution seems to be promising as a long-term antifungal agent. Choline-undecanoate IL is effective and virtually nontoxic and warrants further development.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002433},
	author = {Kim, Sarah and Bispo, Paulo J M and Tanner, Eden E L and Mitragotri, Samir and E Silva, Rafaella N and Gipson, Ilene and Chodosh, James and Behlau, Irmgard and Paschalis, Eleftherios I and Gilmore, Michael S and Dohlman, Claes H}
}
@article {603896,
	title = {The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy.},
	journal = {FASEB J},
	volume = {30},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {1300-5},
	abstract = {Proliferative retinopathic diseases often progress in 2 phases: initial regression of retinal vasculature (phase 1) followed by subsequent neovascularization (NV) (phase 2). The immune system has been shown to aid in vascular pruning in such retinopathies; however, little is known about the role of the alternative complement pathway in the initial vascular regression phase. Using a mouse model of oxygen-induced retinopathy (OIR), we observed that alternative complement pathway-deficient mice (Fb(-/-)) exhibited a mild decrease in vascular loss at postnatal day (P)8 compared with age- and strain-matched controls (P = 0.035). Laser capture microdissection was used to isolate the retinal blood vessels. Expression of the complement inhibitors Cd55 and Cd59 was significantly decreased in blood vessels isolated from hyperoxic retinas compared with those from normoxic control mice. Vegf expression was measured at P8 and found to be significantly lower in OIR mice than in normoxic control mice (P = 0.0048). Further examination of specific Vegf isoform expression revealed a significant decrease in Vegf120 (P = 0.00032) and Vegf188 (P = 0.0092). In conjunction with the major modulating effects of Vegf during early retinal vascular development, our data suggest a modest involvement of the alternative complement pathway in targeting vessels for regression in the initial vaso-obliteration stage of OIR.-Kim, C., Smith, K. E., Castillejos, A., Diaz-Aguilar, D., Saint-Geniez, M., Connor, K. M. The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy.},
	issn = {1530-6860},
	doi = {10.1096/fj.15-280834},
	author = {Kim, Clifford and Smith, Kaylee E and Castillejos, Alexandra and Diaz-Aguilar, Daniel and Saint-Geniez, Magali and Connor, Kip M}
}
@article {468941,
	title = {Characterization of cells from patient-derived fibrovascular membranes in proliferative diabetic retinopathy.},
	journal = {Mol Vis},
	volume = {21},
	year = {2015},
	month = {2015},
	pages = {673-87},
	abstract = {PURPOSE: Epiretinal fibrovascular membranes (FVMs) are a hallmark of proliferative diabetic retinopathy (PDR). Surgical removal of FVMs is often indicated to treat tractional retinal detachment. This potentially informative pathological tissue is usually disposed of after surgery without further examination. We developed a method for isolating and characterizing cells derived from FVMs and correlated their expression of specific markers in culture with that in tissue. METHODS: FVMs were obtained from 11 patients with PDR during diabetic vitrectomy surgery and were analyzed with electron microscopy (EM), comparative genomic hybridization (CGH), immunohistochemistry, and/or digested with collagenase II for cell isolation and culture. Antibody arrays and enzyme-linked immunosorbent assay (ELISA) were used to profile secreted angiogenesis-related proteins in cell culture supernatants. RESULTS: EM analysis of the FVMs showed abnormal vessels composed of endothelial cells with large nuclei and plasma membrane infoldings, loosely attached perivascular cells, and stromal cells. The cellular constituents of the FVMs lacked major chromosomal aberrations as shown with CGH. Cells derived from FVMs (C-FVMs) could be isolated and maintained in culture. The C-FVMs retained the expression of markers of cell identity in primary culture, which define specific cell populations including CD31-positive, alpha-smooth muscle actin-positive (SMA), and glial fibrillary acidic protein-positive (GFAP) cells. In primary culture, secretion of angiopoietin-1 and thrombospondin-1 was significantly decreased in culture conditions that resemble a diabetic environment in SMA-positive C-FVMs compared to human retinal pericytes derived from a non-diabetic donor. CONCLUSIONS: C-FVMs obtained from individuals with PDR can be isolated, cultured, and profiled in vitro and may constitute a unique resource for the discovery of cell signaling mechanisms underlying PDR that extends beyond current animal and cell culture models.},
	issn = {1090-0535},
	author = {Kim, Leo A and Wong, Lindsay L and Amarnani, Dhanesh S and Bigger-Allen, Alexander A and Hu, Yang and Marko, Christina K and Eliott, Dean and Shah, Vinay A and McGuone, Declan and Stemmer-Rachamimov, Anat O and Gai, Xiaowu and D{\textquoteright}Amore, Patricia A and Arboleda-Velasquez, Joseph F}
}
@article {635011,
	title = {Effects of tear gases on the eye.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {4},
	year = {2016},
	month = {2016 Jul-Aug},
	pages = {434-42},
	abstract = {Chemical agents that target the eyes have been a popular choice for law enforcement during riots and for military training for nearly a century. The most commonly used agents are chloroacetophenone (formerly sold as Mace), o-chlorobenzylidene malononitrile, and oleoresin capsicum (OC or pepper spray, current ingredient for Mace). Initially, most severe ocular injuries were caused by the explosive force rather than the chemical itself. The development of sprays reduced the mechanical severity of ocular injuries, but resulted in a variety of chemical injuries. The effects on eyes include conjunctival injection, complete corneal epithelial defects, pseudopterygium, corneal neovascularization, persistent conjunctivalization, corneal opacities, and reduced visual acuity. Current management, based on limited human studies, emphasizes decontamination and symptomatic treatment. We review the literature related to clinical and histopathologic effects of tear gas agents on the eye and their management.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.01.002},
	author = {Kim, Yonwook J and Payal, Abhishek R and Daly, Mary K}
}
@article {1782376,
	title = {Analysis of Uveal Melanoma 5-Year Survival Rates by Medicaid Status: A Nationwide Analysis},
	journal = {Ophthalmic Epidemiol},
	year = {2023},
	month = {2023 Nov 15},
	pages = {1-7},
	abstract = {PURPOSE: The survival outcomes of patients with primary uveal melanomas based on Medicaid status have not been previously discussed in the literature. METHODS: The Surveillance, Epidemiology, and End Results Medicaid database were utilized to identify patients with primary uveal melanomas diagnosed between 2006 and 2013. The Kaplan-Meier method was utilized to construct 5-year survival curves in adult, non-elderly patients. Log-rank testing was used to determine differences in survival rates, and multivariate Cox proportional hazards modeling was utilized to perform adjusted survival analysis. RESULTS: A total of 1,765 patients were included (Medicaid: 81, non-Medicaid: 1684). A total of 1683 (95.4\%) were White. The average age was 51.75 years (SD = 9.5 years). Medicaid patients were more likely to be unmarried, live in a high poverty neighborhood, and live in a rural area (all p \&lt; .001). We observed no significant difference in 5-year survival rates between those enrolled in Medicaid (86.6\%, 95\% CI: 79.1\%1-94.7\%) and those not enrolled in Medicaid (85.5, 95\% CI: 83.8\%-87.2\%) (p = .80). After controlling for socioeconomic and clinical factors, Medicaid enrollment was not associated with an increased risk of mortality compared to non-Medicaid enrollment. Age (aHR: 1.04, 95\% CI: 1.02-1.06, p \&lt; .001) and tumor size \&gt;10 mm (aHR: 3.04, 95\% CI: 1.49-6.21, p = .002) were associated with an increased risk of mortality. CONCLUSION: Medicaid enrollment was not associated with worse cancer-specific 5-year survival. Further research needs to be elicited to better understand the role of Medicaid enrollment in patients with primary uveal melanoma.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2023.2280962},
	author = {Kim, Eric J and Lee, James Y and Ganga, Arjun and Barton, Andrew and Rana, Viren and Araia, Ermias and Adriance, William and Wang, Rachel and Somsasundar, Ponnandai and Kim, Leo A}
}
@article {1016081,
	title = {Screening and Characterization of Drugs That Protect Corneal Endothelial Cells Against Unfolded Protein Response and Oxidative Stress},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {2},
	year = {2017},
	month = {2017 Feb 01},
	pages = {892-900},
	abstract = {Purpose: To screen for and characterize compounds that protect corneal endothelial cells against unfolded protein response (UPR) and oxidative stress. Methods: Bovine corneal endothelial cells (BCECs) were treated for 48 hours with 640 compounds from a Food and Drug Administration (FDA)-approved drug library and then challenged with thapsigargin or H2O2 to induce UPR or oxidative stress, respectively. Cell viability was measured using the CellTiter-Glo survival assay. Selected "hits" were subjected to further dose-response testing, and their ability to modulate expression of UPR and oxidative stress markers was assessed by RT-PCR, Western blot, and measurement of protein carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) adducts in immortalized human corneal endothelial cells (iHCECs). Results: Forty-one drugs at 20 μM and 55 drugs at 100 μM increased survival of H2O2-challenged cells, and 8 drugs at 20 μM and 2 drugs at 100 μM increased survival of thapsigargin-challenged cells, compared with untreated control cells. Nicergoline, ergothioneine, nimesulide, oxotremorine, and mefenamic acid increased survival of both H2O2- and thapsigargin-challenged cells. Oxotremorine altered DNA damage inducible 3 (CHOP) gene expression, glucose-regulated protein 78 kDa (GRP78) and activating transcription factor 4 (ATF4) protein expression, and protein carbonyl and 8-OHdG levels. Mefenamic acid altered GRP78 protein expression and protein carbonyl and 8-OHdG levels. Conclusions: Oxotremorine and mefenamic acid are potential survival factors for corneal endothelial cells under UPR and oxidative stress. The described assay can be further expanded to screen additional drugs for potential therapeutic effect in corneal endothelial diseases such as Fuchs{\textquoteright} endothelial corneal dystrophy.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20147},
	author = {Kim, Eun Chul and Toyono, Tetsuya and Berlinicke, Cynthia A and Zack, Donald J and Jurkunas, Ula and Usui, Tomohiko and Jun, Albert S}
}
@article {1559547,
	title = {Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption: A Gene-Diet Interaction Study from the UK Biobank},
	journal = {Ophthalmology},
	volume = {128},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {866-876},
	abstract = {PURPOSE: We examined the association of habitual caffeine intake with intraocular pressure (IOP) and glaucoma and whether genetic predisposition to higher IOP modified these associations. We also assessed whether genetic predisposition to higher coffee consumption was related to IOP. DESIGN: Cross-sectional study in the UK Biobank. PARTICIPANTS: We included 121 374 participants (baseline ages, 39-73 years) with data on coffee and tea intake (collected 2006-2010) and corneal-compensated IOP measurements in 2009. In a subset of 77 906 participants with up to 5 web-based 24-hour-recall food frequency questionnaires (2009-2012), we evaluated total caffeine intake. We also assessed the same relationships with glaucoma (9286 cases and 189 763 controls). METHODS: We evaluated multivariable-adjusted associations with IOP using linear regression and with glaucoma using logistic regression. For both outcomes, we examined gene-diet interactions using a polygenic risk score (PRS) that combined the effects of 111 genetic variants associated with IOP. We also performed Mendelian randomization using 8 genetic variants associated with coffee intake to assess potential causal effects of coffee consumption on IOP. MAIN OUTCOME MEASURES: Intraocular pressure and glaucoma. RESULTS: Mendelian randomization analysis did not support a causal effect of coffee drinking on IOP (P\&nbsp;\&gt;\&nbsp;0.1). Greater caffeine intake was associated weakly with lower IOP: the highest (>=232 mg/day) versus lowest (\&lt;87 mg/day) caffeine consumption was associated with a 0.10-mmHg lower IOP (Ptrend\&nbsp;= 0.01). However, the IOP PRS modified this association: among those in the highest IOP PRS quartile, consuming \&gt; 480 mg/day versus \&lt; 80 mg/day was associated with a 0.35-mmHg higher IOP (Pinteraction\&nbsp;= 0.01). The relationship between caffeine intake and glaucoma was null (P >= 0.1). However, the IOP PRS also modified this relationship: compared with those in the lowest IOP PRS quartile consuming no caffeine, those in the highest IOP PRS quartile consuming >= 321 mg/day showed a 3.90-fold higher glaucoma prevalence (Pinteraction\&nbsp;= 0.0003). CONCLUSIONS: Habitual caffeine consumption was associated weakly with lower IOP, and the association between caffeine consumption and glaucoma was null. However, among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.12.009},
	author = {Kim, Jihye and Aschard, Hugues and Kang, Jae H and Lentjes, Marleen Ah and Do, Ron and Wiggs, Janey L and Khawaja, Anthony P and Pasquale, Louis R and Modifiable Risk Factors for Glaucoma Collaboration}
}
@article {313171,
	title = {Tamoxifen toxicity in cultured retinal pigment epithelial cells is mediated by concurrent regulated cell death mechanisms.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {4747-58},
	abstract = {PURPOSE: To evaluate the mechanism of tamoxifen-induced cell death in human cultured RPE cells, and to investigate concurrent cell death mechanisms including pyroptosis, apoptosis, and necroptosis. METHODS: Human RPE cells were cultured until confluence and treated with tamoxifen; cell death was measured by detecting LDH release. Tamoxifen-induced cell death was further confirmed by 7-aminoactinomycin D (7-AAD) and annexin V staining. Lysosomal destabilization was assessed using lysosomal-associated membrane protein-1 (LAMP-1) and acridine orange staining. The roles of lysosomal enzymes cathepsin B and L were examined by blocking their activity. Caspase activity was evaluated by caspase-1, -3, -8, and -9 specific inhibition. Cells were primed with IL-1α and treated with tamoxifen; mature IL-1β production was quantified via ELISA. Caspase activity was verified with the fluorochrome-labeled inhibitor of caspases (FLICA) probe specific for each caspase. Regulated cell necrosis or necroptosis was examined with 7-AAD and inhibition of receptor-interacting protein 1 (RIP1) kinase using necrostatin-1 (Nec-1). RESULTS: Cell death occurred within 2 hours of tamoxifen treatment of confluent RPE cells and was accompanied by lysosomal membrane permeabilization. Blockade of cathepsin B and L activity led to a significant decrease in cell death, indicating that lysosomal destabilization and cathepsin release occur prior to regulated cell death. Tamoxifen-induced toxicity was shown to occur through both caspase-dependent and caspase-independent cell death pathways. Treatment of RPE cells with caspase inhibitors and Nec-1 resulted in a near complete rescue from cell death. CONCLUSIONS: Tamoxifen-induced cell death occurs through concurrent regulated cell death mechanisms. Simultaneous inhibition of caspase-dependent and caspase-independent cell death pathways is required to protect cells from tamoxifen. Inhibition of upstream activators, such as the cathepsins, may represent a novel approach to block multiple cell death pathways.},
	keywords = {Blotting, Western, Caspases, Cell Death, Cell Survival, Cells, Cultured, Estrogen Antagonists, Humans, Interleukin-1beta, Lysosomes, Retinal Diseases, Retinal Pigment Epithelium, Tamoxifen},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-13662},
	author = {Kim, Leo A and Amarnani, Dhanesh and Gnanaguru, Gopalan and Tseng, Wen Allen and Vavvas, Demetrios G and D{\textquoteright}Amore, Patricia A}
}
@article {1789111,
	title = {The forgotten protection factor: A nationwide score-based assessment of motorcycle eye protection legislation},
	journal = {J Safety Res},
	volume = {87},
	year = {2023},
	month = {2023 Dec},
	pages = {407-415},
	abstract = {INTRODUCTION: Motorcycle accidents cause millions of deaths and injuries globally. It is estimated that billions of dollars would be saved in the United States alone if safety equipment, such as helmets and eye protection, was ubiquitously worn. Legislation concerning eye protection specifically is understudied and poorly characterized. METHOD: We reviewed all motorcycle-related safety equipment laws in all 50 states of the United States for information regarding eye protection. We graded the rigor of each statute using our six-category Eye Safety Metric and performed a comparative analysis of statutes across all jurisdictions. RESULTS: Fourteen states did not have any statutes regarding eye protection. Among states that did, 23 states had weak statutes (0-2 points), 20 states had moderately stringent statutes (3-4 points), and 7 states had strong statutes (5-6 points). States in western United States tended to have less strict eye protection laws. Twenty-six states had eye protection exemptions for windshields, which are a poor form of eye protection. Six states that had universal helmet laws had no laws requiring eye protection. CONCLUSIONS: We characterized eye protection legislation across the country and found great diversity in the stringency of laws across all jurisdictions. Despite only two states lacking helmet laws, we found that 14 states lacked eye protection laws. These findings from our Eye Safety Metric can be used as a springboard for future research, which can be used to determine the need for and significance of eye safety legislation for motorcyclists and to inform legislative decision-making. PRACTICAL APPLICATIONS: With this research, we hope to further the understanding of legislation regarding eye protection for motorcyclists and help policymakers identify states that need improved eye safety standards.},
	keywords = {Accidents, Traffic, Craniocerebral Trauma, Head Protective Devices, Humans, Motorcycles, Protective Devices, United States},
	issn = {1879-1247},
	doi = {10.1016/j.jsr.2023.08.012},
	author = {Kim, Eric J and Ganga, Arjun and Kim, Leo A}
}
@article {1651356,
	title = {Reproducibility of Neuroretinal Rim Measurements Obtained from High-Density Spectral Domain Optical Coherence Tomography Volume Scans},
	journal = {Clin Ophthalmol},
	year = {2022},
	author = {Kim, J. and Men, CJ and Ratanawongphaibul, K and Papadogeorgou, G and Tsikata, E and Ben-David, GS and Antar, H and Poon, LY and Freeman, M and Park, EA and Guzman Aparicio, MA and de Boer, J F and Chen, T. C.}
}
@article {1619429,
	title = {A Randomized Trial of Photobiomodulation Therapy for Center-Involved Diabetic Macular Edema with Good Visual Acuity (Protocol AE)},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {4},
	year = {2022},
	month = {2022 Apr},
	pages = {298-307},
	abstract = {PURPOSE: To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision. DESIGN: Phase 2 randomized clinical trial. PARTICIPANTS: Participants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the United States. METHODS: One eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months. MAIN OUTCOME MEASURES: Change in CST on spectral-domain OCT at 4 months. RESULTS: From April 2019 to February 2020, 135 adults were randomly assigned to either PBM (n\&nbsp;= 69) or placebo (n\&nbsp;= 66); median age was 62 years, 37\% were women, and 82\% were White. The median device compliance was 92\% with PBM and 95\% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes, with the mean difference (95\% confidence interval [CI]) being\&nbsp;-2 (-20 to 16) μm (P\&nbsp;= 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90\%) PBM eyes and 57 (86\%) placebo eyes at 4 months (adjusted odds ratio [95\% CI]\&nbsp;= 1.30 (0.44-3.83); P\&nbsp;= 0.63). VA decreased by a mean (SD) of\&nbsp;-0.2 (5.5) letters and\&nbsp;-0.6 (4.6) letters in the PBM and placebo groups, respectively (difference [95\% CI]\&nbsp;= 0.4 (-1.3 to 2.0) letters; P\&nbsp;= 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious. CONCLUSIONS: PBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.},
	keywords = {Adult, Angiogenesis Inhibitors, Clinical Trials, Phase II as Topic, Diabetes Mellitus, Diabetic Retinopathy, Female, Humans, Low-Level Light Therapy, Macular Edema, Male, Middle Aged, Randomized Controlled Trials as Topic, Tomography, Optical Coherence, Visual Acuity},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2021.10.003},
	author = {Kim, Judy E and Glassman, Adam R and Josic, Kristin and Melia, Michele and Aiello, Lloyd P and Baker, Carl and Eells, Janis T and Jampol, Lee M and Kern, Timothy S and Marcus, Dennis and Salehi-Had, Hani and Shah, Sandeep N and Martin, Daniel F and Stockdale, Cynthia R and Sun, Jennifer K and DRCR Retina Network}
}
@article {1282131,
	title = {An Infrared Dye-Conjugated Virus-like Particle for the Treatment of Primary Uveal Melanoma},
	journal = {Mol Cancer Ther},
	volume = {17},
	number = {2},
	year = {2018},
	month = {2018 Feb},
	pages = {565-574},
	abstract = {The work outlined herein describes AU-011, a novel recombinant papillomavirus-like particle (VLP) drug conjugate and its initial evaluation as a potential treatment for primary uveal melanoma. The VLP is conjugated with a phthalocyanine photosensitizer, IRDye 700DX, that exerts its cytotoxic effect through photoactivation with a near-infrared laser. We assessed the anticancer properties of AU-011utilizing a panel of human cancer cell lines andusing murine subcutaneous and rabbit orthotopic xenograft models of uveal melanoma. The specificity of VLP binding (tumor targeting), mediated through cell surface heparan sulfate proteoglycans (HSPG), was assessed using HSPG-deficient cells and by inclusion of heparin instudies. Our results provide evidence of potent and selective anticancer activity, bothandAU-011 activity was blocked by inhibiting its association with HSPG using heparin and using cells lacking surface HSPG, indicating that the tumor tropism of the VLP was not affected by dye conjugation and cell association is critical for AU-011-mediated cytotoxicity. Using the uveal melanoma xenograft models, we observed tumor uptake following intravenous (murine) and intravitreal (rabbit) administration and, after photoactivation, potent dose-dependent tumor responses. Furthermore, in the rabbit orthotopic model, which closely models uveal melanoma as it presents in the clinic, tumor treatment spared the retina and adjacent ocular structures. Our results support further clinical development of this novel therapeutic modality that might transform visual outcomes and provide a targeted therapy for the early-stage treatment of patients with this rare and life-threatening disease..},
	issn = {1538-8514},
	doi = {10.1158/1535-7163.MCT-17-0953},
	author = {Kines, Rhonda C and Varsavsky, Isabella and Choudhary, Sanghamitra and Bhattacharya, Debaditya and Spring, Sean and McLaughlin, Roger and Kang, Shin J and Grossniklaus, Hans E and Vavvas, Demetrios and Monks, Stephen and MacDougall, John R and de Los Pinos, Elisabet and Schiller, John T}
}
@article {1297784,
	title = {Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma},
	journal = {PLoS Genet},
	volume = {14},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {e1007145},
	abstract = {Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10-6 for SNP rs76319873. POU6F2 is found in retinal ganglion cells and in corneal limbal stem cells. To test the effect of POU6F2 on CCT we examined the corneas of a Pou6f2-null mice and the corneas were thinner than those of wild-type littermates. In addition, these POU6F2 RGCs die early in the DBA/2J model of glaucoma than most RGCs. Using a mouse genetic reference panel, we identified a transcription factor, Pou6f2, that modulates CCT in the mouse. POU6F2 is also found in a subset of retinal ganglion cells and these RGCs are sensitive to injury.},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1007145},
	author = {King, Rebecca and Struebing, Felix L and Li, Ying and Wang, Jiaxing and Koch, Allison Ashley and Cooke Bailey, Jessica N and Gharahkhani, Puya and International Glaucoma Genetics Consortium and NEIGHBORHOOD Consortium and Macgregor, Stuart and Allingham, R Rand and Hauser, Michael A and Wiggs, Janey L and Geisert, Eldon E}
}
@article {1364497,
	title = {Desmoplastic trichoepithelioma: report of a unique periocular case},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {28},
	number = {5},
	year = {2012},
	month = {2012 Sep-Oct},
	pages = {e121-3},
	abstract = {In a 58-year-old woman with blepharospasm, a slowly enlarging left inferomedial eyelid lesion developed. It measured 3 {\texttimes} 5 mm and was nonulcerated, well-circumscribed, whitish, upraised, and firm. An initial incomplete excision followed by a total repeated excision revealed small squamous microcysts, often exhibiting calcifications and cords of nonclefting basaloid cells embedded in a scirrhous stroma characteristic of desmoplastic trichoepithelioma (DTE). Immunohistochemical investigations disclosed CD34-positive stromal fibroblasts and many CK20-positive Merkel cells located among the epithelial cells, features absent in mimicking sclerosing basal cell carcinoma (BCC). The tumor has not recurred during 6 months of follow up. Besides BCC, the differential diagnosis chiefly concerns syringoma and microcystic adnexal carcinoma. Surgical therapy should aim at complete excision but does not have to be as extensive or aggressive as that used for morpheic or sclerosing BCC because of its lack of diffusely infiltrating margins.},
	keywords = {Antigens, CD34, Biomarkers, Tumor, Blepharospasm, Botulinum Toxins, Type A, Eyelid Neoplasms, Female, Humans, Immunohistochemistry, Keratin-20, Ki-67 Antigen, Middle Aged, Skin Neoplasms},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e318245535a},
	author = {Kirzhner, Maria and Jakobiec, Frederick A and Borodic, Gary}
}
@article {1655727,
	title = {Light-Seq: light-directed in situ barcoding of biomolecules in fixed cells and tissues for spatially indexed sequencing},
	journal = {Nat Methods},
	volume = {19},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {1393-1402},
	abstract = {We present Light-Seq, an approach for multiplexed spatial indexing of intact biological samples using light-directed DNA barcoding in fixed cells and tissues followed by ex situ sequencing. Light-Seq combines spatially targeted, rapid photocrosslinking of DNA barcodes onto complementary DNAs in situ with a one-step DNA stitching reaction to create pooled, spatially indexed sequencing libraries. This light-directed barcoding enables in situ selection of multiple cell populations in intact fixed tissue samples for full-transcriptome sequencing based on location, morphology or protein stains, without cellular dissociation. Applying Light-Seq to mouse retinal sections, we recovered thousands of differentially enriched transcripts from three cellular layers and discovered biomarkers for a very rare neuronal subtype, dopaminergic amacrine cells, from only four to eight individual cells per section. Light-Seq provides an accessible workflow to combine in situ imaging and protein staining with next generation sequencing of the same cells, leaving the sample intact for further analysis post-sequencing.},
	keywords = {Animals, DNA, DNA, Complementary, High-Throughput Nucleotide Sequencing, Mice},
	issn = {1548-7105},
	doi = {10.1038/s41592-022-01604-1},
	author = {Kishi, Jocelyn Y and Liu, Ninning and West, Emma R and Sheng, Kuanwei and Jordanides, Jack J and Serrata, Matthew and Cepko, Constance L and Saka, Sinem K and Peng Yin}
}
@article {439681,
	title = {Plasma Kallikrein-Kinin System as a VEGF-Independent Mediator of Diabetic Macular Edema.},
	journal = {Diabetes},
	volume = {64},
	number = {10},
	year = {2015},
	month = {2015 Oct},
	pages = {3588-99},
	abstract = {This study characterizes the kallikrein-kinin system in vitreous from individuals with diabetic macular edema (DME) and examines mechanisms contributing to retinal thickening and retinal vascular permeability (RVP). Plasma prekallikrein (PPK) and plasma kallikrein (PKal) were increased twofold and 11.0-fold (both P \&lt; 0.0001), respectively, in vitreous from subjects with DME compared with those with a macular hole (MH). While the vascular endothelial growth factor (VEGF) level was also increased in DME vitreous, PKal and VEGF concentrations do not correlate (r = 0.266, P = 0.112). Using mass spectrometry-based proteomics, we identified 167 vitreous proteins, including 30 that were increased in DME (fourfold or more, P \&lt; 0.001 vs. MH). The majority of proteins associated with DME displayed a higher correlation with PPK than with VEGF concentrations. DME vitreous containing relatively high levels of PKal and low VEGF induced RVP when injected into the vitreous of diabetic rats, a response blocked by bradykinin receptor antagonism but not by bevacizumab. Bradykinin-induced retinal thickening in mice was not affected by blockade of VEGF receptor 2. Diabetes-induced RVP was decreased by up to 78\% (P \&lt; 0.001) in Klkb1 (PPK)-deficient mice compared with wild-type controls. B2- and B1 receptor-induced RVP in diabetic mice was blocked by endothelial nitric oxide synthase (NOS) and inducible NOS deficiency, respectively. These findings implicate the PKal pathway as a VEGF-independent mediator of DME.},
	issn = {1939-327X},
	doi = {10.2337/db15-0317},
	author = {Kita, Takeshi and Clermont, Allen C and Murugesan, Nivetha and Zhou, Qunfang and Fujisawa, Kimihiko and Ishibashi, Tatsuro and Aiello, Lloyd Paul and Feener, Edward P}
}
@article {1490464,
	title = {Generation of mouse model of TGFBI-R124C corneal dystrophy using CRISPR/Cas9-mediated homology-directed repair},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Feb 06},
	pages = {2000},
	abstract = {Mutations in transforming growth factor-beta-induced (TGFBI) gene cause clinically distinct types of corneal dystrophies. To delineate the mechanisms driving these dystrophies, we focused on the R124C mutation in TGFBI that causes lattice corneal dystrophy type1 (LCD1) and generated novel transgenic mice harbouring a single amino acid substitution of arginine 124 with cysteine in TGFBI via ssODN-mediated base-pair substitution using CRISPR/Cas9 technology. Eighty percent of homozygous and 9.1\% of heterozygous TGFBI-R124C mice developed a corneal opacity at 40 weeks of age. Hematoxylin and eosin and Masson trichrome staining showed eosinophilic deposits in subepithelial corneal stroma that stained negative for Congo-red. Although amyloid deposition was not observed in TGFBI-R124C mice, irregular amorphous deposits were clearly observed via transmission electron microscopy near the basement membrane. Interestingly, we found that the corneal deposition of TGFBI protein (TGFBIp) was significantly increased in homozygous TGFBI-R124C mice, suggesting a pathogenic role for the mutant protein accumulation. Furthermore, as observed in the LCD1 patients, corneal epithelial wound healing was significantly delayed in TGFBI-R124C mice. In conclusion, our novel mouse model of TGFBI-R124C corneal dystrophy reproduces features of the human disease. This mouse model will help delineate the pathogenic mechanisms of human corneal dystrophy.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-58876-w},
	author = {Kitamoto, Kohdai and Taketani, Yukako and Fujii, Wataru and Inamochi, Aya and Toyono, Tetsuya and Miyai, Takashi and Yamagami, Satoru and Kuroda, Masahiko and Usui, Tomohiko and Ouchi, Yasuo}
}
@article {1645472,
	title = {Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis},
	journal = {Ocul Surf},
	volume = {25},
	year = {2022},
	month = {2022 Jun 23},
	pages = {108-118},
	abstract = {PURPOSE: Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED. METHODS: An article search was performed in PubMed, EMBASE, and Web of Science. 44 studies reporting on age-related ocular changes and 14 large epidemiological studies involving the prevalence of DED were identified. 8 out of 14 epidemiological studies were further analyzed with meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (impact of aging on the prevalence of DED) were combined using one-group meta-analysis in a random-effects model. RESULTS: Meta-analysis revealed the prevalence of DED in the elderly aged 60 years old or older was 5519 of 60107 (9.2\%) and the odds ratio of aging compared to younger age was 1.313 (95\% confidence interval [CI]; 1.107, 1.557). With increasing age, the integrity of the ocular surface and tear film stability decreased. Various inflammatory cells, including senescent-associated T-cells, infiltrated the ocular surface epithelium, lacrimal gland, and meibomian gland, accompanied by senescence-related changes, including accumulation of 8-OHdG and lipofuscin-like inclusions, increased expression of p53 and apoptosis-related genes, and decreased Ki67 positive cells. CONCLUSIONS: The aging process greatly impacts the ocular surface microenvironment, consequently leading to DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2022.06.004},
	author = {Kitazawa, Koji and Inotmata, Takenori and Shih, Kendric and Hughes, Jun-Wei B and Bozza, Niha and Tomioka, Yasufumi and Numa, Kohsaku and Yokoi, Norihiko and Campisi, Judith and Dana, Reza and Sotozono, Chie}
}
@article {1589740,
	title = {National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIa. The 2020 Clinical Implementation and Early Diagnosis Working Group Report},
	journal = {Transplant Cell Ther},
	volume = {27},
	number = {7},
	year = {2021},
	month = {2021 07},
	pages = {545-557},
	abstract = {Recognition of the earliest signs and symptoms of chronic graft-versus-host disease (GVHD) that lead to severe manifestations remains a challenge. The standardization provided by the National Institutes of Health (NIH) 2005 and 2014 consensus projects has helped improve diagnostic accuracy and severity scoring for clinical trials, but utilization of these tools in routine clinical practice is variable. Additionally, when patients meet the NIH diagnostic criteria, many already have significant morbidity and possibly irreversible organ damage. The goals of this early diagnosis project are 2-fold. First, we provide consensus recommendations regarding implementation of the current NIH diagnostic guidelines into routine transplant care, outside of clinical trials, aiming to enhance early clinical recognition of chronic GVHD. Second, we propose directions for future research efforts to enable discovery of new, early laboratory as well as clinical indicators of chronic GVHD, both globally and for highly morbid organ-specific manifestations. Identification of early features of chronic GVHD that have high positive predictive value for progression to more severe manifestations of the disease could potentially allow for future pre-emptive clinical trials.},
	keywords = {Chronic Disease, Consensus, Early Diagnosis, Graft vs Host Disease, Humans, National Institutes of Health (U.S.), United States},
	issn = {2666-6367},
	doi = {10.1016/j.jtct.2021.03.033},
	author = {Kitko, Carrie L and Pidala, Joseph and Schoemans, H{\'e}l{\`e}ne M and Lawitschka, Anita and Flowers, Mary E and Cowen, Edward W and Tkaczyk, Eric and Farhadfar, Nosha and Jain, Sandeep and Steven, Philipp and Luo, Zhonghui K and Ogawa, Yoko and Stern, Michael and Yanik, Greg A and Cuvelier, Geoffrey D E and Cheng, Guang-Shing and Holtan, Shernan G and Schultz, Kirk R and Martin, Paul J and Lee, Stephanie J and Pavletic, Steven Z and Wolff, Daniel and Paczesny, Sophie and Blazar, Bruce R and Sarantopoulos, Stephanie and Socie, Gerard and Greinix, Hildegard and Cutler, Corey}
}
@inbook {1367078,
	title = {Enterococcal Genomics},
	booktitle = {Enterococci: From Commensals to Leading Causes of Drug Resistant Infection [Internet]. Boston: Massachusetts Eye and Ear Infirmary; 2014-. },
	year = {2014},
	abstract = {Available from\&nbsp;http://www.ncbi.nlm.nih.gov/books/NBK190425/},
	author = {Palmer KL and van Schaik W and Willems RJL and Gilmore MS}
}
@article {1474197,
	title = {Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants},
	journal = {Growth Horm IGF Res},
	volume = {50},
	year = {2019},
	month = {2019 Nov 09},
	pages = {1-8},
	abstract = {OBJECTIVE: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. METHODS: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. RESULTS: Thirty seven percent of IGF-1 values during active treatment were \&lt;20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 \&lt; 20 μg/L, gestational age adjusted OR 1.30 (95\% CI 1.03-1.63), p = .026, and 1.57 (95\% CI 1.26-1.97), p \&lt; .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 \&lt; 20 μg/L, gestational age adjusted OR 1.74 (95\% CI 1.19-2.53), p = .004. CONCLUSION: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784).},
	issn = {1532-2238},
	doi = {10.1016/j.ghir.2019.11.001},
	author = {Klevebro, Susanna and Hellgren, Gunnel and Hansen-Pupp, Ingrid and Wackernagel, Dirk and Hallberg, Boubou and Borg, Jan and Pivodic, Aldina and Smith, Lois and Ley, David and Hellstr{\"o}m, Ann}
}
@article {959431,
	title = {Cohort study of growth patterns by gestational age in preterm infants developing morbidity.},
	journal = {BMJ Open},
	volume = {6},
	number = {11},
	year = {2016},
	month = {2016 Nov 17},
	pages = {e012872},
	abstract = {OBJECTIVES: To examine differences in growth patterns in preterm infants developing major morbidities including retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC) and intraventricular haemorrhage (IVH). STUDY DESIGN: Cohort study of 2521 infants born at a gestational age (GA) of 23-30 weeks from 11 level III neonatal intensive care units in USA and Canada, and 3 Swedish population-based cohorts. OUTCOMES: Birth weight and postnatal weight gain were examined relative to birth GA and ROP, BPD, NEC and IVH development. RESULTS: Among infants with a birth GA of 25-30 weeks, birth weight SD score and postnatal weight were lower in those developing ROP and BPD. Infants developing ROP showed lower growth rates during postnatal weeks 7-9 in the 23-24 weeks GA group, during weeks 4-6 in the 25-26 weeks GA group and during weeks 1-5 in the 27-30 weeks GA group. Infants with BPD born at 27-30 weeks GA showed lower growth rates during postnatal weeks 3-5. Infants with NEC had lower growth rates after postnatal week 6 in all GA groups, with no significant differences in birth weight SD score. IVH was not associated with prenatal or postnatal growth. CONCLUSIONS: In this cohort study of extremely preterm infants, we found that the postnatal growth pattern was associated with morbidities such as ROP, BPD and NEC as well as with gestational age at birth.},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2016-012872},
	author = {Klevebro, S and Lundgren, P and Hammar, U and Smith, L E and Bottai, M and Domell{\"o}f, M and L{\"o}fqvist, C and Hallberg, B. and Hellstr{\"o}m, A}
}
@article {1580790,
	title = {Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)},
	journal = {Autophagy},
	year = {2021},
	pages = {1-382},
	abstract = {In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for\&nbsp;bona fide\&nbsp;autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.},
	url = {https://pubmed.ncbi.nlm.nih.gov/33634751/},
	author = {Klionsky, Daniel J and et al}
}
@article {1302195,
	title = {Prosthetic Replacement of the Ocular Surface Ecosystem Treatment of Ocular Surface Disease After Skull Base Tumor Resection},
	journal = {World Neurosurg},
	volume = {110},
	year = {2018},
	month = {2018 Feb},
	pages = {e124-e128},
	abstract = {BACKGROUND: Prosthetic replacement of the ocular surface ecosystem (PROSE) treatment is an effective, nonsurgical therapeutic option for patients with ocular surface disease related to cranial nerve deficits secondary to skull base tumor resection. METHODS: This case series describes the impact of PROSE treatment in patients with symptomatic exposure keratopathy or neurotrophic keratitis after skull base tumor surgery. RESULTS: All patients improved symptomatically and functionally with PROSE treatment, and have had sustained improvement for as long as 3 years. CONCLUSIONS: In postneurosurgical cases in which neurologic function may recover, PROSE treatment offers a safe, nonsurgical treatment option to support the ocular surface during the period of observation awaiting neurologic recovery.},
	issn = {1878-8769},
	doi = {10.1016/j.wneu.2017.10.111},
	author = {Kloek, Carolyn E and Jeng-Miller, Karen W and Jacobs, Deborah S and Dunn, Ian F}
}
@article {382236,
	title = {A broadly applicable surgical teaching method: evaluation of a stepwise introduction to cataract surgery},
	journal = {J Surg Educ},
	volume = {71},
	number = {2},
	year = {2014},
	month = {2014 Mar-Apr},
	pages = {169-75},
	abstract = {OBJECTIVE: Although cataract surgery is one of the most commonly performed surgeries in the country, it is a microsurgical procedure that is difficult to learn and to teach. This study aims to assess the effectiveness of a new method for introducing postgraduate year (PGY)-3 ophthalmology residents to cataract surgery.

SETTING: Hospital-based ophthalmology residency program.

DESIGN: Retrospective cohort study.

PARTICIPANTS: PGY-3 and PGY-4 residents of the Harvard Medical School Ophthalmology Residency from graduating years 2010 to 2012.

RESULTS: In July 2009, a new method of teaching PGY-3 ophthalmology residents cataract surgery was introduced, which was termed "the stepwise introduction to cataract surgery." This curriculum aimed to train residents to perform steps of cataract surgery by deliberately practicing each of the steps of surgery under a structured curriculum with faculty feedback. Assessment methods included surveys administered to the PGY-4 residents who graduated before the implementation of these measures (n = 7), the residents who participated in the first and second years of the new curriculum (n = 16), faculty who teach PGY-4 residents cataract surgery (n = 8), and review of resident Accreditation Council for Graduate Medical Education surgical logs. Resident survey response rate was 100\%. Residents who participated in the new curriculum performed more of each step of cataract surgery in the operating room, spent more time practicing each step of cataract surgery on a cataract surgery simulator during the PGY-3 year, and performed more primary cataract surgeries during the PGY-3 year than those who did not. Faculty survey response rate was 63\%. Faculty noted an increase in resident preparedness following implementation of the new curriculum. There was no statistical difference between the precurriculum and postcurriculum groups in the percentage turnover of cataracts for the first 2 cataract surgery rotations of the PGY-4 year of training.

CONCLUSIONS: The introduction of cataract surgery to PGY-3 residents in an organized, stepwise manner improved resident preparedness for the PGY-4 year of residency. This surgical teaching method can be easily applied to other surgical specialties.},
	keywords = {Adult, Cataract Extraction, General Surgery, Humans, Internship and Residency, Ophthalmology, Retrospective Studies, Teaching},
	issn = {1878-7452},
	doi = {10.1016/j.jsurg.2013.07.007},
	author = {Kloek, Carolyn E and Borboli-Gerogiannis, Sheila and Chang, Kenneth and Kuperwaser, Mark and Newman, Lori R and Lane, Anne Marie and Loewenstein, John I}
}
@article {1078761,
	title = {Differences in Wait Times for Cosmetic Blepharoplasty by ASOPRS Members},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {3},
	year = {2018},
	month = {2018 May/Jun},
	pages = {222-224},
	abstract = {PURPOSE: Adequate access to subspecialty care is of concern to patients and physicians alike. One measure of availability is the wait time for cosmetic procedures. The authors investigated geographical differences in wait times for cosmetic upper eyelid blepharoplasty of American Society of Ophthalmic Plastic and Reconstructive Surgery members across the country.

METHODS: This study surveyed all 533 American Society of Ophthalmic Plastic and Reconstructive Surgery members{\textquoteright} practices in the United States based on the publically available contact information (www.asoprs.org). Scripted telephone calls were made requesting self-referred cosmetic upper eyelid blepharoplasty. Wait times until the first available appointment and time until the first available surgery date were collected.

RESULTS: Of the membership, 387 (72.6\% response rate) respondents offered appointments for cosmetic upper eyelid blepharoplasty. Overall, 84.2\% of respondents were male. Practice breakdown was 83.4\% in private practice and 16.5\% in academic practice. Median wait time until the next available appointment was 14 days (mean 21.2 days, 0-205 days; p = 0.145). Private practice wait time was shorter than academic (median 14 vs. 18 days, mean 19.7 vs. 28.9 days; p =0.004). However, there was wide variability based on region.

CONCLUSIONS: Patients seeking cosmetic upper eyelid blepharoplasty have good access to care by American Society of Ophthalmic Plastic and Reconstructive Surgery members. There are variabilities based on academic versus private practice. Further study can evaluate whether similar findings exist for medically necessary functional procedures. This information may help assess the need for additional practitioners.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000922},
	author = {Knezevic, Alexander and Yoon, Michael K}
}
@article {1347439,
	title = {Transepithelial versus epithelium-off corneal crosslinking for corneal ectasia},
	journal = {J Cataract Refract Surg},
	volume = {44},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {1507-1516},
	abstract = {This review compared the clinical results of transepithelial corneal crosslinking (CXL) to epithelium-off (epi-off) CXL in progressive corneal ectasia using a metaanalysis. The Cochrane databases and Medline were searched for randomized controlled trials (RCTs). Seven RCTs involving 505 eyes that met the eligibility criteria were identified. The epi-off CXL group showed significantly better outcomes in postoperative changes in maximum keratometry (K) during 1-year observation periods. Transepithelial CXL resulted in significantly greater post-treatment central corneal thickness and best spectacle-corrected visual acuity (BSCVA). The presence of a postoperative demarcation line was significantly more frequent after epi-off CXL than that after transepithelial CXL. No statistically significant difference was found between other parameters. Although patients in the transepithelial CXL group demonstrated a greater improvement in BSCVA compared with patients in the epi-off CXL group at the 1\&nbsp;year follow-up, transepithelial CXL had less impact on halting progressive corneal ectasia in terms of maximum K than epi-off CXL.},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2018.08.021},
	author = {Kobashi, Hidenaga and Rong, Shi Song and Ciolino, Joseph B}
}
@article {1295869,
	title = {Impact of Forward and Backward Scattering and Corneal Higher-Order Aberrations on Visual Acuity after Penetrating Keratoplasty},
	journal = {Semin Ophthalmol},
	year = {2018},
	month = {2018 Jan 16},
	pages = {1-9},
	abstract = {PURPOSE: To assess the relationship of forward and backward scattering and corneal higher-order aberrations (HOAs) with corrected distance visual acuity (CDVA) after penetrating keratoplasty (PK). METHODS: This retrospective study comprised 25 eyes of 25 consecutive patients who underwent PK using the VisuMax femtosecond laser system and age-matched 25 eyes of 25 healthy subjects. We quantitatively assessed objective scattering index (OSI) using the double-pass instrument (OQAS II, Visiometrics), corneal densitometry (CD) and corneal HOAs with the Scheimpflug rotating camera (Pentacam HR, Oculus) 1\&nbsp;year postoperatively. RESULTS: The OSI, CD, and corneal HOAs were significantly larger in the PK group than those in the control group (p\&nbsp;<=\&nbsp;0.011). We found significant correlations of logMAR CDVA with the OSI (r\&nbsp;=\&nbsp;0.477, p\&nbsp;=\&nbsp;0.016), and with the anterior, posterior, and total corneal HOAs of the central 4-mm zone (anterior: r\&nbsp;=\&nbsp;0.573, p\&nbsp;=\&nbsp;0.003, posterior: r\&nbsp;=\&nbsp;0.596, p\&nbsp;=\&nbsp;0.002, total: r\&nbsp;=\&nbsp;0.472, p\&nbsp;=\&nbsp;0.017), but no significant association with the CD of the 0-2\&nbsp;mm zone at any layers (anterior: r\&nbsp;=\&nbsp;0.236, p\&nbsp;=\&nbsp;0.257, center: r\&nbsp;=\&nbsp;0.139, p\&nbsp;=\&nbsp;0.506, posterior: r\&nbsp;=\&nbsp;0.073, p\&nbsp;=\&nbsp;0.728, total: r\&nbsp;=\&nbsp;0.212, p\&nbsp;=\&nbsp;0.308). Similar results were obtained when the analysis was repeated with corneal HOAs of the central 6-mm zone and CDs in 2-6\&nbsp;mm zone. CONCLUSIONS: Our pilot study demonstrated that the postoperative CDVA was significantly correlated with OSI and corneal HOAs, but not with backward scattering in post-PK eyes, suggesting that OSI as well as corneal HOAs plays an essential role in postoperative visual performance after PK.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2018.1427767},
	author = {Kobashi, Hidenaga and Kamiya, Kazutaka and Shimizu, Kimiya}
}
@article {961726,
	title = {Randomized Comparison Between Rebamipide Ophthalmic Suspension and Diquafosol Ophthalmic Solution for Dry Eye After Penetrating Keratoplasty.},
	journal = {J Ocul Pharmacol Ther},
	volume = {33},
	number = {1},
	year = {2017},
	pages = {13-18},
	abstract = {PURPOSE: To compare the ocular surfaces of patients treated with rebamipide (REB) ophthalmic suspension or diquafosol (DQS) ophthalmic solution for dry eye syndrome after penetrating keratoplasty (PK). METHODS: A total of 40 eyes of 40 patients who had dry eyes after undergoing PK were enrolled and randomly divided into an REB group and a DQS group. Both REB and DQS groups used each eye drop four times. The tear breakup time (TBUT), corneal fluorescein staining scores, and dry eye-related quality-of-life score (DEQS) were evaluated before treatment, 2 weeks after start of treatment and 4 weeks after start of treatment. RESULTS: We found a significant improvement in TBUT (P \&lt; 0.001, Dunnett{\textquoteright}s test) and fluorescein scores (P \&lt; 0.001) 4 weeks after treatment in the REB group. Similar results were obtained in the DQS group (P \&lt; 0.001 and P = 0.01, respectively). No significant improvements in DEQS were found 4 weeks after treatment in each group (P = 0.15 and P = 0.63, analysis of variance, respectively). No significant differences were seen in these variables and in the changes between the groups after treatment. CONCLUSIONS: REB and DQS may be effective for the management of dry eye syndrome after PK in terms of ocular surface findings. In our study, effects of REB appear to be equivalent to those of DQS in the patients.},
	issn = {1557-7732},
	doi = {10.1089/jop.2016.0096},
	author = {Kobashi, Hidenaga and Kamiya, Kazutaka and Shimizu, Kimiya}
}
@article {1333853,
	title = {Innovative Development of Contact Lenses},
	journal = {Cornea},
	volume = {37 Suppl 1},
	year = {2018},
	month = {2018 Nov},
	pages = {S94-S98},
	abstract = {Contact lenses have been a common means of vision correction for more than half a century. Recent developments have raised the possibility that the next few decades will see a considerable broadening of the range of applications for contact lenses, with associated expansions in the number and type of individuals who consider them a valuable option. The novel applications of contact lenses include treatment platforms for myopic progression, biosensors, and ocular drug delivery. Orthokeratology has shown the most consistent treatment for myopia control with the least side effects. Recent work has resulted in commercialization of a device to monitor intraocular pressure for up to 24 hours, and extensive efforts are underway to develop a contact lens sensor capable of continuous glucose tear film monitoring for the management of diabetes. Other studies on drug-eluting contact lenses have focused on increasing the release duration through molecular imprinting, use of vitamin E, and increased drug binding to polymers by sandwiching a poly (lactic-co-glycolic acid) layer in the lens. This review demonstrates the potential for contact lenses to provide novel opportunities for refractive management, diagnosis, and management of diseases.},
	keywords = {Biosensing Techniques, Contact Lenses, Diabetes Mellitus, Drug Delivery Systems, Glucose, Humans, Monitoring, Physiologic, Ocular Hypertension, Orthokeratologic Procedures, Refractive Errors, Tears},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001725},
	author = {Kobashi, Hidenaga and Ciolino, Joseph B}
}
@article {882956,
	title = {Dry Eye After Small Incision Lenticule Extraction and Femtosecond Laser-Assisted LASIK: Meta-Analysis.},
	journal = {Cornea},
	volume = {36},
	number = {1},
	year = {2017},
	pages = {85-91},
	abstract = {PURPOSE: To compare postoperative ocular surface integrity and innervation between small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). METHODS: The Cochrane Central Register of Controlled Trials, PubMED, and EMBASE were searched for prospective comparative studies. Trials meeting the selection criteria were quality appraised, and the data were extracted by 2 independent authors. The weighted mean differences (WMDs) and 95\% confidence intervals (CIs) were used to compare dry eye examinations and corneal subbasal nerve density (SMILE-FS-LASIK). RESULTS: The study covered 5 trials. No significant difference was found in the Schirmer test score between both groups (WMD = -1.91 and 0.27; 95\% CI, -5.02 to 1.20 and -0.99 to 1.54; P = 0.23 and 0.67 at 1- and 6-month follow-ups, respectively). Tear breakup time in the SMILE group significantly exceeded that in the FS-LASIK group (WMD = 0.65 and 1.14; 95\% CI, 0.20-1.10 and 0.18-2.10; P = 0.004 and 0.02, at 1- and 6-month follow-ups, respectively). Ocular surface disease index scores were significantly better in the SMILE group 6 months postoperatively (WMD = -10.12, 95\% CI, -16.07 to -4.18, P = 0.0008). No significant difference was found in tear osmolarity between both groups (WMD = -5.19 and -6.37; 95\% CI, -17.15 to 6.76 and -22.74 to 10.00; P = 0.39 and 0.45 at 1- and 6-month follow-ups, respectively). Higher corneal sensitivity was observed in the SMILE group 1 and 6 months postoperatively (WMD = 11.35 and 3.49; 95\% CI, 7.29-15.40 and 1.76-5.21; P \&lt; 0.00001 and \&lt;0.0001, at 1- and 6-month follow-ups, respectively). Corneal subbasal nerve density was also significantly higher in SMILE-treated eyes than it was in FS-LASIK-treated eyes 1 month postoperatively (WMD = 4.72, 95\% CI, 1.10-8.34, P = 0.01). CONCLUSIONS: According to this meta-analysis, the SMILE procedure has fewer negative impacts on the ocular surface and corneal innervation than does FS-LASIK. Furthermore, SMILE shows superiority over FS-LASIK by a exhibiting a lower risk of postoperative dry eye.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000999},
	author = {Kobashi, Hidenaga and Kamiya, Kazutaka and Shimizu, Kimiya}
}
@article {931101,
	title = {[Limbal stem cell deficiency management. A review].},
	journal = {J Fr Ophtalmol},
	volume = {39},
	number = {9},
	year = {2016},
	month = {2016 Nov},
	pages = {791-803},
	abstract = {Limbal stem cell deficiency is predominantly caused by severe eye burns resulting in a decreased or a complete ablation of the regenerative potential of these stem cells. The inability to reconstruct the corneal epithelium further leads conjunctivalization of the gimbal-epithelial barrier. These abnormalities collectively result in the progressive opacification of the cornea responsible for blindness that is driven by chronic corneal ulceration and neovascularization. The underlying pathology of the cornea affects the homeostasis of the neighboring conjunctiva, eyelids, and tear film. Therefore, the ocular reconstruction to treat limbal stem cell deficiency is quite prolonged and involves a continued treatment plan. The management of limbal stem cell deficiency has undergone a multitude of changes over the past several decades.\&nbsp;The understanding of limbal anatomy and physiology, as well as therapeutic advances in the stem cell field have propelled the development of new treatments offering new hope to severely disabled patients. Cultivated limbal epithelial and oral mucosal epithelial transplantations are therefore viable alternatives that could be utilized for the treatment of limbal stem cell deficiency.},
	issn = {1773-0597},
	doi = {10.1016/j.jfo.2016.08.001},
	author = {Kocaba, V and Damour, O and Auxenfans, C and Burillon, C}
}
@article {314146,
	title = {CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {5871-7},
	abstract = {PURPOSE: We characterized antigen-presenting cell (APC)-relevant chemokine receptor expression in dry eye disease (DED), and investigated the effect of topical CC chemokine receptor (CCR)-7 blockade specifically on Th17 cell immunity and dry eye disease severity. METHODS: We induced DED in female C57BL/6 mice. Chemokine receptor expression by corneal APCs was characterized using immunohistochemistry. To determine the functional role of CCR7 in DED, mice were treated topically with either anti-CCR7, a control isotype antibody, or left untreated, and clinical disease severity, Th17 responses, and molecular markers of DED were quantified. RESULTS: Frequencies of CD11b(+) cells and their chemokine expression were increased in the cornea of DED mice. Mice treated topically with anti-CCR7 antibody displayed a significant reduction in clinical disease severity and Th17 response compared to the isotype and untreated groups. Topical CCR7 blockade was effective in ameliorating DED in its acute and chronic stages. CONCLUSIONS: Our findings suggest that CCR7-mediated trafficking of APCs drives the induction and maintenance of Th17 immunity in DED and that CCR7 blockade is effective in suppressing the immunopathogenic mechanisms in DED.},
	keywords = {Animals, Antigens, CD11b, Corneal Stroma, Disease Models, Animal, Dry Eye Syndromes, Female, Flow Cytometry, Immunohistochemistry, Mice, Mice, Inbred C57BL, Receptors, CCR7, Th17 Cells},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14481},
	author = {Kodati, Shilpa and Chauhan, Sunil K and Chen, Yihe and Dohlman, Thomas H and Karimian, Parisa and Saban, Daniel and Dana, Reza}
}
@article {1364498,
	title = {Utility of ocular ultrasonography in diagnosing infectious endophthalmitis in patients with media opacities},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {242-5},
	abstract = {Assessment of patients with infectious endophthalmitis is frequently limited by media opacities, and ocular ultrasonography is routinely performed in this setting. We examined the literature to assess the level of evidence for the utility of ocular ultrasonography in these patients. Common ultrasonographic findings reported include low amplitude mobile echoes, vitreous membranes, and thickening of the retina and choroid. Based on the available evidence, we conclude that ocular ultrasound may be a useful adjunct in guiding treatment and minimizing complications. While positive findings may be confirmatory in cases in which the clinical suspicion is high, ocular ultrasound alone cannot be used to prove or to exclude the diagnosis of infectious endophthalmitis.},
	keywords = {Choroid, Endophthalmitis, Eye Diseases, Eye Infections, Humans, Hypertrophy, Retina, Ultrasonography, Vitreous Body},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.711417},
	author = {Kohanim, Sahar and Daniels, Anthony B and Huynh, Nancy and Eliott, Dean and Chodosh, James}
}
@article {1748471,
	title = {Background polygenic risk modulates the association between glaucoma and cardiopulmonary diseases and measures: an analysis from the UK Biobank},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {1112-1118},
	abstract = {AIMS: To assess whether associations of cardiopulmonary conditions and markers with glaucoma differ by background genetic risk for primary open angle glaucoma (POAG). METHODS: We constructed a POAG polygenic risk score (PRS) using genome-wide association study summary statistics from a large cross-ancestry meta-analysis. History of glaucoma (including self-report and codes for POAG, {\textquoteright}other glaucoma{\textquoteright} or unspecified glaucoma), history of common cardiopulmonary conditions and cardiopulmonary measures were assessed in the UK Biobank. Stratifying by PRS decile 1 (lowest risk) versus decile 10 (highest risk), separate multivariable models were estimated to assess the associations of cardiopulmonary diseases or factors with glaucoma, adjusting for age, sex, smoking and medication use. A Bonferroni correction was used to adjust p values for multiple comparisons. RESULTS: Individuals in POAG PRS decile 1 (417 cases, 44 458 controls; mean age 56.8 years) and decile 10 (2135 cases, 42 413 controls; mean age 56.7 years) were included. Within decile 1, glaucoma cases had significantly higher glycated haemoglobin (38.5 vs 35.9 mmol/mol) and higher prevalence of diabetes (17.5\% vs 6.5\%), dyslipidaemia (31.2\% vs 18.3\%) and chronic kidney disease (CKD) (6.7\% vs 2.0\%) than controls (adjusted p\&lt;0.0013 for each). Within decile 10, glaucoma was associated with higher prevalence of dyslipidaemia (27.7\% vs 17.3\%, p=6.9E-05). The magnitude of association between glaucoma and diabetes, CKD and glycated haemoglobin differed between deciles 1 and 10 (contrast test p value for difference \&lt;0.05). CONCLUSION: The relations between systemic conditions and glaucoma vary by underlying genetic predisposition to POAG, with larger associations among those who developed glaucoma despite low genetic risk.},
	keywords = {Biological Specimen Banks, Diabetes Mellitus, Genome-Wide Association Study, Glaucoma, Glaucoma, Open-Angle, Glycated Hemoglobin, Humans, Middle Aged, Risk Factors, United Kingdom},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-320305},
	author = {Kolli, Ajay and Sekimitsu, Sayuri and Wang, Jiali and Segre, Ayellet and Friedman, David and Tobias Elze and Pasquale, Louis R and Wiggs, Janey and Zebardast, Nazlee}
}
@article {1619427,
	title = {Lessons Learned From 2 Large Community-based Glaucoma Screening Studies},
	journal = {J Glaucoma},
	volume = {30},
	number = {10},
	year = {2021},
	month = {2021 10 01},
	pages = {875-877},
	abstract = {Community-based screening programs have had limited success in preventing vision loss from glaucoma due to overall low prevalence of glaucoma, screening limitations, and barriers to follow-up appointments. This editorial highlights lessons learned from 2 large prospective trials: the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study and the Screening To Prevent Glaucoma Study. While some lessons are specific to ophthalmology, many lessons are applicable to screening for asymptomatic diseases in underserved, vulnerable communities.},
	keywords = {Diagnostic Techniques, Ophthalmological, Follow-Up Studies, Glaucoma, Humans, Intraocular Pressure, Prospective Studies},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001920},
	author = {Kolomeyer, Natasha N and Katz, Leslie J and Hark, Lisa A and Wahl, Madison and Gajwani, Prateek and Aziz, Kanza and Myers, Jonathan S and Friedman, David S}
}
@article {1059771,
	title = {Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity},
	journal = {Sci Rep},
	volume = {7},
	year = {2017},
	month = {2017 Apr 21},
	pages = {46581},
	abstract = {Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth. Here, in a series of experiments, using human uveal melanoma cells (MEL 270), human embryonic kidney cells (HEK) and breast cancer cells (MCF7) we showed that Verteporfin-induced HMWC require the presence of light. Furthermore, we showed that the mechanism of this cross-linking, which involves both singlet oxygen and radical generation, can occur very efficiently even after lysis of the cells, if the lysate is not protected from ambient light. This work offers a better understanding regarding VP{\textquoteright}s mechanisms of action and suggests caution when one studies the non-light mediated actions of this drug.},
	issn = {2045-2322},
	doi = {10.1038/srep46581},
	author = {Konstantinou, Eleni K and Notomi, Shoji and Kosmidou, Cassandra and Brodowska, Katarzyna and Al-Moujahed, Ahmad and Nicolaou, Fotini and Tsoka, Pavlina and Gragoudas, Evangelos and Miller, Joan W and Young, Lucy H and Vavvas, Demetrios G}
}
@article {1608579,
	title = {Birt-Hogg-Dub{\'e} syndrome associated with chorioretinopathy and nyctalopia: a case report and review of the literature},
	journal = {Ophthalmic Genet},
	volume = {44},
	number = {2},
	year = {2023},
	month = {2023 Apr},
	pages = {175-181},
	abstract = {PURPOSE: To report a rare case of Birt-Hogg-Dub{\'e} Syndrome (BHD) with progressive chorioretinopathy. METHODS: Case report. RESULTS: A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy. CONCLUSION: BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities. ABBREVIATIONS: BHD: Birt-Hogg-Dub{\'e} syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive.},
	keywords = {Birt-Hogg-Dube Syndrome, Central Serous Chorioretinopathy, Female, Humans, Middle Aged, Night Blindness},
	issn = {1744-5094},
	doi = {10.1080/13816810.2021.1961281},
	author = {Konstantinou, Eleni K and Shaikh, Noreen and Ramsey, David J}
}
@article {1474201,
	title = {Learning Descemet Membrane Endothelial Keratoplasty: A Survey of U.S. Corneal Surgeons},
	journal = {Cornea},
	volume = {39},
	number = {5},
	year = {2020},
	month = {2020 May},
	pages = {590-593},
	abstract = {PURPOSE: The transition to Descemet membrane endothelial keratoplasty (DMEK) is frequently challenging, requiring the adoption of new techniques, skills, and methods. We sought to draw on surgeons{\textquoteright} initial experiences with DMEK to characterize the learning curve associated with this procedure and identify factors that could be linked to the frequency of primary graft failure (PGF) in the first 10 cases. METHODS: We invited corneal surgeons based in the United States who started performing the DMEK procedure within the past 2 years to answer a 12-question survey using an online survey platform. We analyzed quantitative and qualitative data. A Fisher exact test was used to determine whether preoperative approaches to preparation were associated with decreased PGF rates. RESULTS: A total of 100 US-based corneal surgeons replied from 34 of 50 states. Of these, 68\% reported that DMEK comprised a majority of their endothelial keratoplasty cases. Approximately half of surgeons (52\%) had performed more than 20 DMEK cases by the time of the survey, and 51\% felt equally comfortable performing DMEK relative to Descemet stripping endothelial keratoplasty. Among the respondents, 37\% answered that they had experienced PGF in the first 10 cases. Scrubbing in with an experienced colleague before surgery was associated with a decreased likelihood of at least one case of PGF (31\%, P = 0.049), but not participation in a wet lab with an experienced instructor or mentor (38\%, P = 0.50), nor having an eye bank representative present in the operating room (43\%, P = 0.886). CONCLUSIONS: The collective experience of 100 surgeons beginning DMEK confirms the importance of mentorship and that the accompaniment of an experienced colleague during the learning curve is associated with lower rates of PGF.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002203},
	author = {Koo, Ellen H and Pineda, Roberto and Afshari, Natalie and Eghrari, Allen}
}
@article {1359934,
	title = {Global Practice Patterns in the Management of Infantile Cataracts},
	journal = {Eye Contact Lens},
	volume = {44 Suppl 2},
	year = {2018},
	month = {2018 Nov},
	pages = {S292-S296},
	abstract = {OBJECTIVES: Surveys are an important tool to assess the impact of research on physicians{\textquoteright} approach to patient care. This survey was conducted to assess current practice patterns in the management of infantile cataracts in light of the findings of the Infant Aphakia Treatment Study. METHODS: Pediatric ophthalmologists were emailed a link to the survey using newsletters from American Association of Pediatric Ophthalmology and Strabismus, World Society of Pediatric Ophthalmology and Strabismus, and the Pediatric Listserv. The 17-question survey was anonymous and active during July to August 2016. RESULTS: One hundred twenty-five respondents (North America, 65\%; Asia, 12\%; Europe, 9\%; and other, 14\%) reported operating on pediatric cataracts. Most practice in a university setting (55\%). There was a strong consensus that unilateral cataract surgery should be performed between ages 4 to 6 weeks and aphakic contact lenses should be used to optically correct their eyes, particularly in children <=6 months of age. For bilateral cataracts, there was a trend for surgeons to perform cataract surgery at an older age than unilateral cataract surgery. Surgeons who performed less than 5 versus greater than 20 pediatric cataract surgeries/year were more likely to use aphakic contact lenses in children undergoing cataract surgery more than 6 months of age (62\% vs. 35\%, P=0.04). Most respondents (73\%) indicated that the Infant Aphakia Treatment Study had changed how they manage unilateral congenital cataracts. CONCLUSION: Most pediatric cataract surgeons perform congenital cataract surgery between ages 4 to 6 weeks and use aphakic contact lenses for initial optical correction in infants less than 6 months. Surgeons have equal preference for intraocular lenses and contact lenses in infants more than 6 months of age.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000461},
	author = {Koo, Euna B and VanderVeen, Deborah K and Lambert, Scott R}
}
@article {1364499,
	title = {Comparative genomics of vancomycin-resistant Staphylococcus aureus strains and their positions within the clade most commonly associated with Methicillin-resistant S. aureus hospital-acquired infection in the United States},
	journal = {MBio},
	volume = {3},
	number = {3},
	year = {2012},
	month = {2012},
	abstract = {UNLABELLED: Methicillin-resistant Staphylococcus aureus (MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistant S. aureus (VRSA) infection in the United States-all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546 and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift in dprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition. IMPORTANCE: Invasive methicillin-resistant Staphylococcus aureus (MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistant S. aureus (VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546 from enterococcal donors. All acquisitions of Tn1546 so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.},
	keywords = {Amino Acid Sequence, Bacterial Proteins, Cross Infection, Genomics, Humans, Methicillin Resistance, Methicillin-Resistant Staphylococcus aureus, Molecular Sequence Data, Phylogeny, Sequence Alignment, Staphylococcal Infections, Staphylococcus aureus, United States, Vancomycin Resistance},
	issn = {2150-7511},
	doi = {10.1128/mBio.00112-12},
	author = {Kos, Veronica N and Desjardins, Christopher A and Griggs, Allison and Cerqueira, Gustavo and Van Tonder, Andries and Holden, Matthew T G and Godfrey, Paul and Palmer, Kelli L and Bodi, Kip and Mongodin, Emmanuel F and Wortman, Jennifer and Feldgarden, Michael and Lawley, Trevor and Gill, Steven R and Haas, Brian J and Birren, Bruce and Gilmore, Michael S}
}
@article {1295870,
	title = {Issues with the Specificity of Immunological Reagents for NLRP3: Implications for Age-related Macular Degeneration},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Jan 11},
	pages = {461},
	abstract = {Contradictory data have been presented regarding the implication of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in age-related macular degeneration (AMD), the leading cause of vision loss in the Western world. Recognizing that antibody specificity may explain this discrepancy and in line with recent National Institutes of Health (NIH) guidelines requiring authentication of key biological resources, the specificity of anti-NLRP3 antibodies was assessed to elucidate whether non-immune RPE cells express NLRP3. Using validated resources, NLRP3 was not detected in human primary or human established RPE cell lines under multiple inflammasome-priming conditions, including purported NLRP3 stimuli in RPE such as DICER1 deletion and Alu RNA transfection. Furthermore, NLRP3 was below detection limits in ex vivo macular RPE from AMD patients, as well as in human induced pluripotent stem cell (hiPSC)-derived RPE from patients with overactive NLRP3 syndrome (Chronic infantile neurologic cutaneous and articulate, CINCA syndrome). Evidence presented in this study provides new data regarding the interpretation of published results reporting NLRP3 expression and upregulation in RPE and addresses the role that this inflammasome plays in AMD pathogenesis.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-17634-1},
	author = {Kosmidou, Cassandra and Efstathiou, Nikolaos E and Hoang, Mien V and Notomi, Shoji and Konstantinou, Eleni K and Hirano, Masayuki and Takahashi, Kosuke and Maidana, Daniel E and Tsoka, Pavlina and Young, Lucy and Gragoudas, Evangelos S and Olsen, Timothy W and Morizane, Yuki and Miller, Joan W and Vavvas, Demetrios G}
}
@article {503976,
	title = {The Risk of Intraocular Pressure Elevation inPediatric Noninfectious Uveitis.},
	journal = {Ophthalmology},
	volume = {122},
	number = {10},
	year = {2015},
	month = {2015 Oct},
	pages = {1987-2001},
	abstract = {PURPOSE: To characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric noninfectious uveitis. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: Nine hundred sixteen children (1593 eyes) younger than 18 years at presentation with noninfectious uveitis followed up between January 1978 and December 2007 at 5 academic uveitis centers in the United States. METHODS: Medical records review by trained, certified experts. MAIN OUTCOME MEASURES: Prevalence and incidence of IOP of 21 mmHg or more and 30 mmHg or more and incidence of a rise in IOP by 10 mmHg or more. To avoid underascertainment, outcomes were counted as present when IOP-lowering therapies were in use. RESULTS: Initially, 251 (15.8\%) and 46 eyes (2.9\%) had IOP >=21 mmHg and >=30 mmHg, respectively. Factors significantly associated with presenting IOP elevation included age of 6 to 12 years (versus other pediatric ages), prior cataract surgery, pars plana vitrectomy, duration of uveitis >=6 months, contralateral IOP elevation, presenting visual acuity worse than 20/40, and topical corticosteroid use (in a dose-response relationship). The median follow-up was 1.25 years (interquartile range, 0.4-3.66). The estimated incidence of any observed IOP elevation to >=21 mmHg, to >=30 mmHg, and increase in IOP by >=10 mmHg was 33.4\%, 14.8\%, and 24.4\%, respectively, within 2 years. Factors associated with IOP elevation included pars plana vitrectomy, contralateral IOP elevation (adjusted hazard ratio [aHR], up to 9.54; P \&lt; 0.001), and the use of topical (aHR, up to 8.77 that followed a dose-response relationship; P \&lt; 0.001), periocular (aHR, up to 7.96; P \&lt; 0.001), and intraocular (aHR, up to 19.7; P\&nbsp;\&lt;\&nbsp;0.001) corticosteroids. CONCLUSIONS: Intraocular pressure elevation affects a large minority of children with noninfectious uveitis. Statistically significant risk factors include IOP elevation or use of IOP-lowering treatment in the contralateral eye and local corticosteroid use that demonstrated a dose-and route of administration-dependent relationship. In contrast, use of immunosuppressive drug therapy did not increase such risk. Pediatric eyes with noninfectious uveitis should be followed up closely for IOP elevation, especially when strong risk factors such as the use of local corticosteroids and contralateral IOP elevation are present.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.06.041},
	author = {Kothari, Srishti and Foster, C Stephen and Pistilli, Maxwell and Liesegang, Teresa L and Daniel, Ebenezer and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Lawrence, Scott D and Kempen, John H and Systemic Immunosuppressive Therapy for~Eye~Diseases Research Group}
}
@article {1452974,
	title = {Correlating Changes in the Macular Microvasculature and Capillary Network to Peripheral Vascular Pathologic Features in Familial Exudative Vitreoretinopathy},
	journal = {Ophthalmol Retina},
	volume = {3},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {597-606},
	abstract = {PURPOSE: To evaluate the macular microvasculature in patients with familial exudative vitreoretinopathy (FEVR) using OCT angiography (OCTA) and to assess for peripheral vascular changes using widefield fluorescein angiography (WFA). DESIGN: Multicenter, retrospective, comparative, observational case series. PARTICIPANTS: We identified 411 patients with FEVR, examined between September 2014 and June 2018. Fifty-seven patients with FEVR and 60 healthy controls had OCTA images of sufficient quality for analysis. METHODS: Custom software was used to assess for layer-specific, quantitative changes in vascular density and morphologic features on OCTA by way of vessel density (VD), skeletal density (SD), fractal dimension (FD), vessel diameter index (VDI), and foveal avascular zone (FAZ). Widefield fluorescein angiography images were reviewed for peripheral vascular changes including capillary dropout, late-phase angiographic posterior and peripheral vascular leakage (LAPPEL), vascular dragging, venous-venous shunts, and arteriovenous shunts. MAIN OUTCOME MEASURES: Macular microvascular parameters on OCTA and peripheral angiographic findings on WFA. RESULTS: OCT angiography analysis of 117 patients (187 eyes; 92 FEVR patients and 95 control participants) demonstrated significantly reduced VD, SD, and FD and greater VDI in patients with FEVR compared with controls in the nonsegmented retina, superficial retinal layer (SRL), and deep retinal layer (DRL). The FAZ was larger compared with that in control eyes in the DRL (P \&lt; 0.0001), but not the SRL (P\&nbsp;= 0.52). Subanalysis by FEVR stage showed the same microvascular changes compared with controls for all parameters. Widefield fluorescein angiography analysis of 95 eyes (53 patients) with FEVR demonstrated capillary nonperfusion in all eyes: 47 eyes (49.5\%) showed LAPPEL, 32 eyes (33.7\%) showed vascular dragging, 30 eyes (31.6\%) had venous-venous shunts, and 33 eyes (34.7\%) had arteriovenous shunts. Decreasing macular VD on OCTA correlated with increasing peripheral capillary nonperfusion on WFA. Decreasing fractal dimension on OCTA correlated with increasing LAPPEL severity on WFA. CONCLUSIONS: Patients with FEVR demonstrated abnormalities in the macular microvasculature and capillary network, in addition to the peripheral retina. The macular microvascular parameters on OCTA may serve as biomarkers of changes in the retinal periphery on WFA.},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.02.013},
	author = {Koulisis, Nicole and Moysidis, Stavros N and Yonekawa, Yoshihiro and Dai, Yi Ling and Burkemper, Bruce and Wood, Edward H and Lertjirachai, Itsara and Todorich, Bozho and Khundkar, Tahsin Z and Chu, Zhongdi and Wang, Ruikang K and Williams, George A and Drenser, Kimberly A and Capone, Antonio and Trese, Michael T and Nudleman, Eric}
}
@article {1511507,
	title = {A new storage solution for the hypothermic preservation of corneal grafts: an experimental study},
	journal = {Cell Tissue Bank},
	volume = {21},
	number = {3},
	year = {2020},
	month = {2020 Sep},
	pages = {507-521},
	abstract = {In this experimental study we used for the first time Tiprotec as a solution for corneal preservation and cold storage. We compared the resultant endothelial cell morphology and viability with this obtained after preservation of the ex-vivo corneas with both usual standard techniques: conventional cold storage (using Eusol-C) and organ culture. This prospective, in vitro, 3-armed parallel study was performed with the use of 90 porcine corneas (examined for their endothelial quality and transparency) randomly selected for preservation in three storage methods (each 30 corneas): organ culture, standard cold storage (Eusol-C) and experimental cold storage (Tiprotec) Endothelium cell quantity and quality as well as corneal opacification were assessed. The degree of endothelial transparency was significantly reduced over time with all preservation media, without any significant difference among the three groups at any point of time. A reduction in endothelial cell density was also observed with all three preservation media after 30\&nbsp;days of storage without statistically significant differences between groups. The number of hexagonal and pentagonal endothelium cells was significantly reduced overtime in all media with significantly more hexagonal and pentagonal in the organ culture group compared to the cold storage groups. We could show that the cryopreservation medium Tiprotec, used until now for the preservation of vascular grafts, was of similar quality compared to the medium Eusol-C for the hypothermic storage of corneal tissue for an extended period of time up to 30\&nbsp;days. In comparison to organic culture with culture medium KII, both Tiprotec and Eusol-C were found less effective in preserving endothelial cell quality, as assessed by the morphometric analysis, and viability, as assessed by the degree of vacuolization at least up to the 30th day of storage. However, both, Tiprotec- and Eusol-C-preserved corneas demonstrated a certain capacity to recover after their submission in organ culture.},
	issn = {1573-6814},
	doi = {10.1007/s10561-020-09838-z},
	author = {Koulouri, Ismini and Hellwinkel, Olaf and Alten{\"a}hr, Sibylle and Spitzer, Martin and Fritz, Stefan and Feuerstacke, Jana and Filev, Filip}
}
@article {1405412,
	title = {Central Scotoma a Year After Motor Vehicle Crash},
	journal = {JAMA Ophthalmol},
	year = {2018},
	month = {2018 Dec 27},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.5421},
	author = {Koulouri, Ismini and Vingopoulos, Filippos and Vavvas, Demetrios G}
}
@article {1817311,
	title = {Progressive Keratoconus in a Patient With Severe Pectus Excavatum and a Cartilage Oligomeric Matrix Protein Gene Mutation: A Case Report},
	journal = {Eye Contact Lens},
	volume = {50},
	number = {1},
	year = {2024},
	month = {2024 Jan 01},
	pages = {48-51},
	abstract = {INTRODUCTION: Keratoconus is a progressive ocular disorder associated with numerous systemic diseases, many of which affect the musculoskeletal system. Although the etiology and pathophysiology of the disorder remain elusive, recent studies suggest a significant role of genetic predisposition in the pathogenesis of keratoconus. This case report aims to elucidate a potential genetic association in a patient presenting with keratoconus, severe pectus excavatum, generalized muscular weakness, and skeletal deformities.

CASE DESCRIPTION: A 31-year-old Iranian man presented with progressively diminishing vision in both eyes over the years, eventually diagnosed with keratoconus. The patient{\textquoteright}s history and further examination indicated generalized muscular weakness, skeletal deformities, and severe pectus excavatum with cardiac and large vessel displacement. Whole-exome sequencing identified two heterozygous gene variants: one in the Cartilage Oligomeric Matrix Protein (COMP) gene and another in the Regulating Synaptic Membrane Exocytosis 1 gene. The patient{\textquoteright}s systemic and ocular symptoms, combined with the gene variants identified, suggested a connective tissue systemic disorder, potentially within the clinical spectrum of COMPopathies.

CONCLUSION: This is the first documented case of bilateral progressive keratoconus associated with severe pectus excavatum, generalized musculoskeletal dystrophy, and a COMP gene mutation. It highlights the necessity of continued search into the pathogenic genes of keratoconus, particularly in cases with coexisting systemic manifestations, to further our understanding of the etiology and pathogenesis of this complex disease.},
	keywords = {Adult, Cartilage Oligomeric Matrix Protein, Funnel Chest, Humans, Iran, Keratoconus, Male, Muscle Weakness, Mutation},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000001053},
	author = {Kounatidou, Nefeli Eleni and Kondylis, Georgios and Klavdianou, Olga and Venkateswaran, Nandini and Fryssira, Eleni and Palioura, Sotiria}
}
@article {1364500,
	title = {Pharmacokinetic study of vitreous and serum concentrations of triamcinolone acetonide after posterior sub-tenon{\textquoteright}s injection},
	journal = {Am J Ophthalmol},
	volume = {153},
	number = {5},
	year = {2012},
	month = {2012 May},
	pages = {939-48},
	abstract = {PURPOSE: To compare a theoretical pharmacokinetic model of triamcinolone acetonide after posterior sub-Tenon{\textquoteright}s injection with experimental serum and undiluted vitreous triamcinolone acetonide concentrations obtained during pars plana vitrectomy. DESIGN: Clinical-practice, prospective, interventional case series study. METHODS: This study compared computer-modeled triamcinolone acetonide diffusion after posterior sub-Tenon{\textquoteright}s injection with triamcinolone acetonide levels in experimental undiluted vitreous and serum samples from 57 patients undergoing vitrectomy assessed via mass spectrometry and high-pressure liquid chromatography. At least 5 pairs of samples were collected at each of 7 time points (1 day, 3 days, and 1, 2, 3, 4, and 8 weeks) after triamcinolone acetonide injection, with 6 controls without injection. Cortisol levels were measured in 31 sets of samples. RESULTS: The theoretical model predicted that triamcinolone acetonide levels in systemic blood, vitreous, and choroidal extracellular matrix would plateau after 3 days at 15 ng/mL, 227 ng/mL and 2230 ng/mL, respectively. Experimental vitreous levels of triamcinolone peaked at 111 ng/mL at day 1, then reached a plateau in the range 15 to 25 ng/mL, while serum triamcinolone levels peaked at day 3 near 35 ng/mL and plateaued near 2 to 8 ng/mL. Serum triamcinolone and cortisol levels were inversely correlated (Spearman -0.42, P = .02). CONCLUSIONS: The theoretical model predicts efficient delivery of triamcinolone acetonide from the posterior sub-Tenon{\textquoteright}s space to the extracellular choroidal matrix. The experimental findings demonstrate low levels of serum triamcinolone that alter systemic cortisol levels and higher vitreous levels lasting at least 1 month. Both assessments support trans-scleral delivery of posterior sub-Tenon{\textquoteright}s triamcinolone.},
	keywords = {Biological Availability, Chromatography, High Pressure Liquid, Computer Simulation, Glucocorticoids, Humans, Hydrocortisone, Injections, Intraocular, Mass Spectrometry, Models, Theoretical, Tenon Capsule, Triamcinolone Acetonide, Vitrectomy, Vitreous Body},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2011.10.021},
	author = {Kovacs, Kyle and Wagley, Sushant and Quirk, Matthew T and Ceron, Olga M and Silva, Paolo A and Singh, Ravinder J and Gukasyan, Hovhannes J and Arroyo, Jorge G}
}
@article {560221,
	title = {Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {11},
	year = {2015},
	month = {2015 Oct 1},
	pages = {6523-30},
	abstract = {PURPOSE: To characterize the angiogenic and inflammatory vitreous biomarker profiles in a spectrum of ischemic retinopathies, including neovascular glaucoma. METHODS: This institutional review board-approved study retrospectively analyzed 80 undiluted vitreous samples obtained during pars vitrectomy. The specimens were frozen (-80{\textdegree}C) and sent for concentration analysis of 34 proteins by Bio-Plex Pro assays. Specimens were divided into four groups: patients undergoing epiretinal membrane (ERM) peeling and/or macular hole (MH) surgery with no history of diabetes (non-DM group), patients undergoing ERM peeling, and/or MH surgery with a history of diabetes (DM group), patients with proliferative diabetic retinopathy (PDR group), and patients with neovascular glaucoma (NVG group). Parametric and nonparametric analyses of demographics and cytokine levels were performed using SPSS. RESULTS: There were no significant differences in demographics among cohorts. Numerous proteins were significantly elevated between non-DM and DM (G-CSF, sCD40L, Endoglin, IL-6, placental growth factor [PlGF], VEGF-D), DM and PDR (leptin, IL-8, PlGF, VEGF-A), and PDR and NVG (G-CSF, leptin, TIE-2, sCD40L, EGF, HB-EGF, IL-6, IL-8, PlGF, TNF-α). Only PlGF was significantly elevated between each successive cohort. The most potent drivers of NVG were PlGF, VEGF-A, IL-6, and IL-8. CONCLUSIONS: While the role of angioproliferative growth factors is well documented in ischemic retinopathy, our study delineates the importance of inflammatory and previously underreported angiogenic proteins. It also demonstrates a significant incremental increase in certain factors with increasing levels of ischemia. Both of these findings may guide the development of future therapies for ischemic retinopathies.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-16793},
	author = {Kovacs, Kyle and Marra, Kyle V and Yu, Gina and Wagley, Sushant and Ma, Jie and Teague, Gianna C and Nandakumar, Namrata and Lashkari, Kameran and Arroyo, Jorge G}
}
@article {1658659,
	title = {Role of inflammatory cells in pathophysiology and management of diabetic retinopathy},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {6},
	year = {2022},
	month = {2022 Nov-Dec},
	pages = {1563-1573},
	abstract = {Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus. Several inflammatory cells and proteins, including macrophages and microglia, cytokines, and vascular endothelial growth factors, are found to play a significant role in the development and progression of DR. Inflammatory cells play a significant role in the earliest changes seen in DR including the breakdown of the blood retinal barrier leading to leakage of blood into the retina. They also have an important role in the pathogenesis of more advanced stage of proliferative diabetic retinopathy, leading to neovascularization, vitreous hemorrhage, and tractional retinal detachment. In this review, we examine the function of numerous inflammatory cells involved in the pathogenesis, progression, and role as a potential therapeutic target in DR. Additionally, we explore the role of inflammation following treatment of DR.},
	keywords = {Cytokines, Diabetes Mellitus, Diabetic Retinopathy, Humans, Retina, Vascular Endothelial Growth Factors, Vitreous Hemorrhage},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2022.07.008},
	author = {Kovoor, Elias and Chauhan, Sunil K and Hajrasouliha, Amir}
}
@article {1647906,
	title = {Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome},
	journal = {Ann Rheum Dis},
	volume = {81},
	number = {10},
	year = {2022},
	month = {2022 Oct},
	pages = {1453-1464},
	abstract = {OBJECTIVES: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. METHODS: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. RESULTS: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients{\textquoteright} primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation.Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. CONCLUSION: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy.},
	keywords = {Amyloidosis, Animals, Cohort Studies, Gain of Function Mutation, Hereditary Autoinflammatory Diseases, Humans, Inflammation, Mice, Mutation, NF-kappa B, Protein Kinases, Quality of Life, Serum Amyloid A Protein, Syndrome, Tumor Necrosis Factor Inhibitors},
	issn = {1468-2060},
	doi = {10.1136/annrheumdis-2022-222629},
	author = {Kozycki, Christina Torres and Kodati, Shilpa and Huryn, Laryssa and Wang, Hongying and Warner, Blake M and Jani, Priyam and Hammoud, Dima and Abu-Asab, Mones S and Jittayasothorn, Yingyos and Mattapallil, Mary J and Tsai, Wanxia Li and Ullah, Ehsan and Zhou, Ping and Tian, Xiaoying and Soldatos, Ariane and Moutsopoulos, Niki and Kao-Hsieh, Marie and Heller, Theo and Cowen, Edward W and Lee, Chyi-Chia Richard and Toro, Camilo and Kalsi, Shelley and Khavandgar, Zohreh and Baer, Alan and Beach, Margaret and Long Priel, Debra and Nehrebecky, Michele and Rosenzweig, Sofia and Romeo, Tina and Deuitch, Natalie and Brenchley, Laurie and Pelayo, Eileen and Zein, Wadih and Sen, Nida and Yang, Alexander H and Farley, Gary and Sweetser, David A and Briere, Lauren and Yang, Janine and de Oliveira Poswar, Fabiano and Schwartz, Ida Vanessa D and Silva Alves, Tamires and Dusser, Perrine and Kon{\'e}-Paut, Isabelle and Touitou, Isabelle and Titah, Salah Mohamed and van Hagen, Petrus Martin and van Wijck, Rogier T A and van der Spek, Peter J and Yano, Hiromi and Benneche, Andreas and Apalset, Ellen M and Jansson, Ragnhild Wivestad and Caspi, Rachel R and Kuhns, Douglas Byron and Gadina, Massimo and Takada, Hidetoshi and Ida, Hiroaki and Nishikomori, Ryuta and Verrecchia, Elena and Sangiorgi, Eugenio and Manna, Raffaele and Brooks, Brian P and Sobrin, Lucia and Hufnagel, Robert B and Beck, David and Shao, Feng and Ombrello, Amanda K and Aksentijevich, Ivona and Kastner, Daniel L and Undiagnosed Diseases Network}
}
@article {1470989,
	title = {Cerebral/Cortical Visual Impairment: A Need to Reassess Current Definitions of Visual Impairment and Blindness},
	journal = {Semin Pediatr Neurol},
	volume = {31},
	year = {2019},
	month = {2019 Oct},
	pages = {25-29},
	abstract = {Cerebral/cortical visual impairment (CVI) is characterized by higher order visual dysfunction caused by injury to the retrogeniculate visual pathways and brain structures which subserve visual processing. CVI has become the leading cause of significant vision loss in children in developed countries, but continues to be an under-recognized cause of visual disability with respect to services aimed at maximizing visual development. Current criteria which are used to define visual disability rely on measures of visual acuity and visual field. Many children who require specialized vision services do not qualify, because these standard definitions of vision impairment do not account for CVI. In order to appropriately identify patients with CVI and offer the resources which may positively impact functional use of vision, the definition of visual impairment and blindness needs to be modified. This commentary calls for a change in the definition of visual impairment and blindness to acknowledge those persons with brain-based vision impairment.},
	issn = {1558-0776},
	doi = {10.1016/j.spen.2019.05.005},
	author = {Kran, Barry S and Lawrence, Linda and Mayer, D Luisa and Heidary, Gena}
}
@article {1532336,
	title = {Accelerating ophthalmic artificial intelligence research: the role of an open access data repository},
	journal = {Curr Opin Ophthalmol},
	volume = {31},
	number = {5},
	year = {2020},
	month = {2020 Sep},
	pages = {337-350},
	abstract = {PURPOSE OF REVIEW: Artificial intelligence has already provided multiple clinically relevant applications in ophthalmology. Yet, the explosion of nonstandardized reporting of high-performing algorithms are rendered useless without robust and streamlined implementation guidelines. The development of protocols and checklists will accelerate the translation of research publications to impact on patient care. RECENT FINDINGS: Beyond technological scepticism, we lack uniformity in analysing algorithmic performance generalizability, and benchmarking impacts across clinical settings. No regulatory guardrails have been set to minimize bias or optimize interpretability; no consensus clinical acceptability thresholds or systematized postdeployment monitoring has been set. Moreover, stakeholders with misaligned incentives deepen the landscape complexity especially when it comes to the requisite data integration and harmonization to advance the field. Therefore, despite increasing algorithmic accuracy and commoditization, the infamous {\textquoteright}implementation gap{\textquoteright} persists. Open clinical data repositories have been shown to rapidly accelerate research, minimize redundancies and disseminate the expertise and knowledge required to overcome existing barriers. Drawing upon the longstanding success of existing governance frameworks and robust data use and sharing agreements, the ophthalmic community has tremendous opportunity in ushering artificial intelligence into medicine. By collaboratively building a powerful resource of open, anonymized multimodal ophthalmic data, the next generation of clinicians can advance data-driven eye care in unprecedented ways. SUMMARY: This piece demonstrates that with readily accessible data, immense progress can be achieved clinically and methodologically to realize artificial intelligence{\textquoteright}s impact on clinical care. Exponentially progressive network effects can be seen by consolidating, curating and distributing data amongst both clinicians and data scientists.},
	keywords = {Access to Information, Algorithms, Artificial Intelligence, Biomedical Research, Humans, Ophthalmology},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000678},
	author = {Kras, Ashley and Celi, Leo A and Miller, John B}
}
@article {1559539,
	title = {The Challenge of Managing Bilateral Acute Angle-closure Glaucoma in the Presence of Active SARS-CoV-2 Infection},
	journal = {J Glaucoma},
	volume = {30},
	number = {3},
	year = {2021},
	month = {2021 03 01},
	pages = {e50-e53},
	abstract = {PURPOSE: To report a case of bilateral acute angle-closure glaucoma associated with hyponatremia in the setting of chlorthalidone use and SARS-CoV-2 infection, and to demonstrate the challenges of managing this patient given her infectious status. METHODS: This was a case report. CASE: A 65-year-old woman taking chlorthalidone for hypertension presented to the emergency room with headache, pain, and blurry vision in both eyes and was found to be in bilateral acute angle closure. On laboratory investigation, she was severely hyponatremic and also tested positive for SARS-CoV-2. B-scan ultrasound demonstrated an apparent supraciliary effusion in the right eye. Following stabilization of her intraocular pressures with medical management, she ultimately underwent cataract extraction with iridectomies and goniosynechiolysis in both eyes. CONCLUSIONS: We report a rare case of bilateral acute angle-closure glaucoma associated with hyponatremia. Chlorthalidone use and perhaps SARS-CoV-2 infection may have contributed to this electrolyte abnormality and unique clinical presentation. In addition, we discuss the challenges of managing this complex patient with active SARS-CoV-2 infection during the pandemic.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001763},
	author = {Krawitz, Brian D and Sirinek, Portia and Doobin, David and Nanda, Tavish and Ghiassi, Maryam and Horowitz, Jason D and Liebmann, Jeffrey M and De Moraes, Carlos G}
}
@article {1603852,
	title = {Stakeholders{\textquoteright} Perceptions of a School-Based Eye Care Programme in Baltimore, MD},
	journal = {Ophthalmic Epidemiol},
	volume = {29},
	number = {3},
	year = {2022},
	month = {2022 Jun},
	pages = {252-261},
	abstract = {PURPOSE: To explore stakeholders{\textquoteright} perceptions of a school-based vision programme (SBVP). METHODS: We conducted 20 focus groups with 105 parents and teachers at schools in Baltimore, MD, that participated in a SBVP. Facilitators used a semi-structured interview guide to discuss participants{\textquoteright} perceptions of the SBVP. Focus groups were audio-recorded, transcribed, and coded using inductive thematic analysis. RESULTS: Participant perceptions fell into three categories: benefits of school-based eye care, limitations of school-based eye care, and observation of impact. The majority of participants had positive comments about the programme; benefits included convenience (location, time, and cost), the comprehensive nature of the programme, the quality of the eyeglasses and ability to receive replacements, and a positive screening/exam experience. Limitations of programme impact were related to communication and organisation, the time to receive the glasses, missed instructional time, and uncertainty about screenings. Observations of impact included academic and classroom improvements, as well as visual and other health improvements. CONCLUSION: Parents and teachers reported mostly positive perceptions regarding the SBVP. Their appreciation for the convenience underscores that location, cost, time, and comprehensive services are crucial aspects for implementing a successful programme. To maximize impact, programs must also implement robust communication campaigns that integrate into the schools{\textquoteright} workflow to help parents and teachers stay engaged in the process from start to finish.},
	keywords = {Baltimore, Eyeglasses, Focus Groups, Humans, Parents, Schools},
	issn = {1744-5086},
	doi = {10.1080/09286586.2021.1946825},
	author = {Kretz, Alyssa M and Vongsachang, Hursuong and Friedman, David S and Callan, Jonathan and Wahl, Madison and Mukherjee, M Rani and Neitzel, Amanda and Collins, Megan E}
}
@article {1043241,
	title = {The human immune response to Toxoplasma: Autophagy versus cell death},
	journal = {PLoS Pathog},
	volume = {13},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {e1006176},
	issn = {1553-7374},
	doi = {10.1371/journal.ppat.1006176},
	author = {Krishnamurthy, Shruthi and Konstantinou, Eleni K and Young, Lucy H and Gold, Daniel A and Saeij, Jeroen P J}
}
@article {959436,
	title = {Overexpression of Soluble Fas Ligand following Adeno-Associated Virus Gene Therapy Prevents Retinal Ganglion Cell Death in Chronic and Acute Murine Models of Glaucoma.},
	journal = {J Immunol},
	volume = {197},
	number = {12},
	year = {2016},
	month = {2016 Dec 15},
	pages = {4626-4638},
	abstract = {Glaucoma is a multifactorial disease resulting in the death of retinal ganglion cells (RGCs) and irreversible blindness. Glaucoma-associated RGC death depends on the proapoptotic and proinflammatory activity of membrane-bound Fas ligand (mFasL). In contrast to mFasL, the natural cleavage product, soluble Fas ligand (sFasL) inhibits mFasL-mediated apoptosis and inflammation and, therefore, is an mFasL antagonist. DBA/2J mice spontaneously develop glaucoma and, predictably, RGC destruction is exacerbated by expression of a mutated membrane-only FasL gene that lacks the extracellular cleavage site. Remarkably, one-time intraocular adeno-associated virus-mediated gene delivery of sFasL provides complete and sustained neuroprotection in the chronic DBA/2J and acute microbead-induced models of glaucoma, even in the presence of elevated intraocular pressure. This protection correlated with inhibition of glial activation, reduced production of TNF-α, and decreased apoptosis of RGCs and loss of axons. These data indicate that cleavage of FasL under homeostatic conditions, and the ensuing release of sFasL, normally limits the neurodestructive activity of FasL. The data further support the notion that sFasL, and not mFasL, contributes to the immune-privileged status of the eye.},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1601488},
	author = {Krishnan, Anitha and Fei, Fei and Jones, Alexander and Busto, Patricia and Marshak-Rothstein, Ann and Ksander, Bruce R and Gregory-Ksander, Meredith}
}
@article {1364501,
	title = {Neuro-imaging: a review for the general ophthalmologist},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {192-6},
	abstract = {The diagnosis of many neuro-ophthalmic conditions is facilitated with neuro-imaging. The two main modalities are Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Clinicians who refer patients for either of these techniques must not only know which of them to choose, but also where the imaging should be performed (e.g. brain, orbit), whether or not contrast is indicated, and if angiography should be supplemented. These complexities often result in imaging studies that are either unneeded or unhelpful. The goal of this manuscript is to provide a practical set of guidelines for the general ophthalmologist of how to choose the correct parameters for neuro-imaging studies.},
	keywords = {Brain Diseases, Diagnostic Techniques, Ophthalmological, Eye Diseases, General Practitioners, Humans, Magnetic Resonance Imaging, Ophthalmology, Practice Guidelines as Topic, Tomography, X-Ray Computed},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.708815},
	author = {Kruger, Joshua M and Lessell, Simmons and Cestari, Dean M}
}
@article {1363133,
	title = {An update on the genetics of comitant strabismus},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {438-41},
	abstract = {Genetics play a significant role in the development of comitant strabismus and elucidating the relevant mechanisms that cause it may lead to the development of new therapeutic options. The genetics of strabismus are complex and involve the interactions of multiple genes. This article reviews the progress that has been made in the understanding of the genetic causes of comitant strabismus including linkage studies that have identified a variety of candidate sites, RNA and protein studies that have identified genes with altered regulation, and a study that establishes a role for genetic imprinting in comitant strabismus.},
	keywords = {Chromosomes, Human, Pair 7, Genetic Linkage, Humans, Strabismus},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825298},
	author = {Kruger, Joshua M and Mansouri, Behzad and Cestari, Dean M}
}
@article {1354361,
	title = {Ocular flutter as the presenting sign of lung adenocarcinoma},
	journal = {Digit J Ophthalmol},
	volume = {20},
	number = {1},
	year = {2014},
	month = {2014},
	pages = {4-6},
	abstract = {Ocular flutter is a rare ophthalmic finding that could represent paraneoplastic phenomena. In adults it is most commonly associated with small cell lung cancer (SCLC). Most patients also present with other neurological defects. We report the case of a 75-year-old woman who presented with isolated ocular flutter. The ensuing workup was significant for an early lung adenocarcinoma that would not have been biopsied otherwise due to its small size. To our knowledge, this is the first reported case of isolated ocular flutter as the presenting symptom of non-SCLC.},
	keywords = {Adenocarcinoma, Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Nystagmus, Pathologic, Paraneoplastic Syndromes, Ocular},
	issn = {1542-8958},
	doi = {10.5693/djo.02.2013.10.002},
	author = {Kruger, Joshua M and Yonekawa, Yoshihiro and Skidd, Philip and Cestari, Dean M}
}
@article {1445354,
	title = {Third-Party Coverage for Aphakic Contact Lenses for Children},
	journal = {Transl Vis Sci Technol},
	volume = {8},
	number = {3},
	year = {2019},
	month = {2019 May},
	pages = {41},
	issn = {2164-2591},
	doi = {10.1167/tvst.8.3.41},
	author = {Kruger, Stacey J and VanderVeen, Deborah K and Freedman, Sharon F and Bothun, Erick and Drews-Botsch, Carolyn D and Lambert, Scott R and Infant Aphakia Study Group}
}
@article {1354362,
	title = {Infliximab for the treatment of refractory noninfectious Uveitis: a study of 88 patients with long-term follow-up},
	journal = {Ophthalmology},
	volume = {121},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {358-364},
	abstract = {OBJECTIVE: To establish the safety and efficacy of infliximab for the treatment of refractory noninfectious uveitis. DESIGN: Retrospective, interventional, noncomparative cohort study. PARTICIPANTS: Eighty-eight patients from a single-center private practice. METHODS: Patients with chronic, recalcitrant uveitis treated with infliximab (Remicade; Janssen Biotech, Inc., Titusville, NJ) were identified through an electronic medical record database. All charts were reviewed for sex, diagnosis, location of inflammation, presence of vasculitis, prior immunomodulatory treatments, duration of infliximab treatment, dose received, secondary side effects, and other medications continued while receiving treatment with infliximab. MAIN OUTCOME MEASURES: The primary outcome measures were the rate of remission, time to remission, relapse rate, failure rate, and patient tolerance. Additional analysis aimed to identity risk factors that would predict a higher success rate of infliximab to treat various types of noninfectious uveitis. RESULTS: Of the 72 patients (81.8\%) who achieved clinical remission while being treated with infliximab, 42 (58.3\%) required additional immunomodulatory medications. At 7, 18.1, and 44.7 weeks, 25\%, 50\%, and 75\% of patients, respectively, achieved clinical remission off all corticosteroids. Thirty-two patients (36.4\%) experienced at least 1 side effect while on infliximab therapy, and 17 patients (19.3\%) discontinued treatment secondary to 1 or more intolerable side effects. The most common adverse effects were skin rash (9.1\%) and fatigue (8\%). Factors associated with a higher chance to achieve clinical remission were nonidiopathic uveitis (P \&lt; 0.001), intermediate or panuveitis (P \&lt; 0.001), absence of vasculitis (P \&lt; 0.001), and a starting dose >=5 mg/kg (P \&lt; 0.011). CONCLUSIONS: Infliximab induces a high rate of complete clinical remission in recalcitrant uveitis and is well tolerated by most patients.},
	keywords = {Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, Chronic Disease, Cohort Studies, Female, Follow-Up Studies, Humans, Infliximab, Male, Retrospective Studies, Time Factors, Treatment Failure, Treatment Outcome, Uveitis},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2013.07.019},
	author = {Kruh, Jonathan N and Yang, Paul and Suelves, Ana M and Foster, C Stephen}
}
@article {469031,
	title = {Evaluation of the Effect of N-Acetylcysteine on Protein Deposition on Contact Lenses in Patients with the Boston Keratoprosthesis Type I.},
	journal = {J Ocul Pharmacol Ther},
	volume = {31},
	number = {6},
	year = {2015},
	month = {2015 Jul-Aug},
	pages = {314-22},
	abstract = {PURPOSE: To establish the efficacy of topical N-acetylcysteine (NAC) as a treatment to reduce protein deposition on the contact lens surface. METHODS: In this prospective, nonrandomized clinical trial, a total of 10 eyes (9 patients) were enrolled from a single center. All patients had a prior ocular history of either a Boston Keratoprosthesis type I or trichiasis from Stevens-Johnson syndrome, which necessitated full-time contact lens wear. Four visits were required to complete the study. During visit 1, a new contact lens was inserted and a baseline examination was performed. Visit 2 served as the control month, whereas visits 3 and 4 were month 1 and 2 on treatment with 20\% NAC. At the end of each visit the contact lens was replaced. The lenses from visit 2 (control month-without NAC) and from visit 3 (treatment month-with NAC) were collected for proteomic analysis. The main outcome measures were to quantify protein deposition, as well as to assess the visual acuity and ocular surface symptoms before and after treatment. RESULTS: Topical NAC resulted in a 20\% decrease in protein deposition. This correlated with a trend for improvement in visual acuity and increased subjective improvement in vision at month 1 (P=0.0153) and 2 (P=0.0016). CONCLUSIONS: NAC reduced protein deposition, decreased ocular surface symptoms, and improved contact lens transparency, thereby providing increased optical clarity.},
	issn = {1557-7732},
	doi = {10.1089/jop.2015.0010},
	author = {Kruh, Jonathan N and Kruh-Garcia, Nicole A and Foster, C Stephen}
}
@article {1629444,
	title = {The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {63},
	number = {1},
	year = {2022},
	month = {2022 Jan 03},
	pages = {19},
	abstract = {Purpose: The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to describe the phenotypic spectrum, and to compare it to albinism. Subjects and Methods: We retrospectively collected molecular, ophthalmic, and electrophysiological data of 28 patients molecularly confirmed with FHONDA from the Netherlands (9), Israel (13), France (2), and the United States of America (4). We compared the data to that of 133 Dutch patients with the 3 most common types of albinism in the Netherlands: oculocutaneous albinism type 1 (49), type 2 (41), and ocular albinism (43). Results: Patients with FHONDA had a total of 15 different mutations in SLC38A8, of which 6 were novel. Excluding missing data, all patients had moderate to severe visual impairment (median visual acuity [VA] = 0.7 logMAR, interquartile range [IQR] = 0.6-0.8), nystagmus (28/28), and grade 4 foveal hypoplasia (17/17). Misrouting was present in all nine tested patients. None of the patients had any signs of hypopigmentation of skin and hair. VA in albinism was better (median = 0.5 logMAR, IQR = 0.3-0.7, P 0.006) and the phenotypes were more variable: 14 of 132 without nystagmus, foveal hypoplasia grades 1 to 4, and misrouting absent in 16 of 74. Conclusions: Compared to albinism, the FHONDA syndrome appears to have a more narrow phenotypic spectrum, consisting of nonprogressive moderately to severely reduced VA, nystagmus, severe foveal hypoplasia, and misrouting. The co-occurrence of nystagmus, foveal hypoplasia, and misrouting in the absence of hypopigmentation implies that these abnormalities are not caused by lack of melanin, which has important implications for understanding the pathogenesis of these features.},
	issn = {1552-5783},
	doi = {10.1167/iovs.63.1.19},
	author = {Kruijt, Charlotte C and Gradstein, Libe and Bergen, Arthur A and Florijn, Ralph J and Arveiler, Benoit and Lasseaux, Eulalie and Zanlonghi, Xavier and Bagdonaite-Bejarano, Laura and Fulton, Anne B and Yahalom, Claudia and Blumenfeld, Anat and Perez, Yonatan and Birk, Ohad S and de Wit, Gerard C and Schalij-Delfos, Nicoline E and van Genderen, Maria M}
}
@article {1761821,
	title = {Polymorphic parasitic larvae cooperate to build swimming colonies luring hosts},
	journal = {Curr Biol},
	volume = {33},
	number = {20},
	year = {2023},
	month = {2023 Oct 23},
	pages = {4524-4531.e4},
	abstract = {Parasites have evolved a variety of astonishing strategies to survive within their hosts, yet the most challenging event in their personal chronicles is the passage from one host to another. It becomes even more complex when a parasite needs to pass through the external environment. Therefore, the free-living stages of parasites present a wide range of adaptations for transmission. Parasitic flatworms from the group Digenea (flukes) have free-living larvae, cercariae, which are remarkably diverse in structure and behavior.1,2 One of the cercariae transmission strategies is to attain a prey-like appearance for the host.3 This can be done through the formation of a swimming aggregate of several cercariae adjoined together by their tails.4 Through the use of live observations and light, electron, and confocal microscopy, we described such a supposedly prey-mimetic colony comprising cercariae of two distinct morphotypes. They are functionally specialized: larger morphotype (sailors) enable motility, and smaller morphotype (passengers) presumably facilitate infection. The analysis of local read alignments between the two samples reveals that both cercaria types have identical 18S, 28S, and 5.8S rRNA genes. Further phylogenetic analysis of these ribosomal sequences indicates that our specimen belongs to the digenean family Acanthocolpidae, likely genus Pleorchis. This discovery provides a unique example and a novel insight into how morphologically and functionally heterogeneous individuals of the same species cooperate to build colonial organisms for the purpose of infection. This strategy bears resemblance to the cooperating castes of the same species found among insects.5.},
	keywords = {Animals, Cercaria, Humans, Larva, parasites, Phylogeny, Swimming, Trematoda},
	issn = {1879-0445},
	doi = {10.1016/j.cub.2023.08.090},
	author = {Krupenko, Darya and Miroliubov, Aleksei and Kryukov, Emil and Faure, Louis and Minemizu, Ryo and Haag, Lars and Lundgren, Magnus and Kameneva, Polina and Kastriti, Maria Eleni and Adameyko, Igor}
}
@article {1470993,
	title = {Phenotype delineation of ZNF462 related syndrome},
	journal = {Am J Med Genet A},
	volume = {179},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {2075-2082},
	abstract = {Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79\%) and a minority has autism spectrum disorder (33\%). Characteristic facial features include ptosis (83\%), down slanting palpebral fissures (58\%), exaggerated Cupid{\textquoteright}s bow/wide philtrum (54\%), and arched eyebrows (50\%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25\% of individuals, hypotonia in half, and structural heart defects in 21\%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features.},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.61306},
	author = {Kruszka, Paul and Hu, Tommy and Hong, Sungkook and Signer, Rebecca and Cogn{\'e}, Benjamin and Isidor, Betrand and Mazzola, Sarah E and Giltay, Jacques C and van Gassen, Koen L I and England, Eleina M and Pais, Lynn and Ockeloen, Charlotte W and Sanchez-Lara, Pedro A and Kinning, Esther and Adams, Darius J and Treat, Kayla and Torres-Martinez, Wilfredo and Bedeschi, Maria F and Iascone, Maria and Blaney, Stephanie and Bell, Oliver and Tan, Tiong Y and Delrue, Marie-Ange and Jurgens, Julie and Barry, Brenda J and Engle, Elizabeth C and Savage, Sarah K and Fleischer, Nicole and Martinez-Agosto, Julian A and Boycott, Kym and Zackai, Elaine H and Muenke, Maximilian}
}
@article {313141,
	title = {ABCB5 is a limbal stem cell gene required for corneal development and repair},
	journal = {Nature},
	volume = {511},
	number = {7509},
	year = {2014},
	month = {2014 Jul 17},
	pages = {353-7},
	abstract = {Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far. Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5) marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated human or murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC-deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs in mice and p63α-positive LSCs in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.},
	keywords = {Animals, Apoptosis, ATP-Binding Cassette Transporters, ATP-Binding Cassette, Sub-Family B, Member 1, Biomarkers, Cell Differentiation, Cell Proliferation, Female, Humans, Limbus Corneae, Male, Mice, Mice, Knockout, Molecular Sequence Data, Regeneration, Stem Cell Transplantation, Stem Cells, Transcription Factors, Tumor Suppressor Proteins, Wound Healing},
	issn = {1476-4687},
	doi = {10.1038/nature13426},
	author = {Ksander, Bruce R and Kolovou, Paraskevi E and Wilson, Brian J and Saab, Karim R and Guo, Qin and Ma, Jie and McGuire, Sean P and Gregory, Meredith S and Vincent, William J B and Perez, Victor L and Cruz-Guilloty, Fernando and Kao, Winston W Y and Call, Mindy K and Tucker, Budd A and Zhan, Qian and Murphy, George F and Lathrop, Kira L and Alt, Clemens and Mortensen, Luke J and Lin, Charles P and Zieske, James D and Frank, Markus H and Frank, Natasha Y}
}
@article {1623356,
	title = {A novel, sensitive, and widely accessible besifloxacin quantification method by HPLC-fluorescence: Application to an ocular pharmacokinetic study},
	journal = {J Chromatogr B Analyt Technol Biomed Life Sci},
	volume = {1185},
	year = {2021},
	month = {2021 Nov 15},
	pages = {123010},
	abstract = {Besifloxacin has been embraced for the treatment of ocular bacterial infections. While LC-MS/MS has been used in investigating BSF pharmacokinetics, those costly instruments are not universally available and have complicated requirements for operation and maintenance. Additionally, pharmacokinetics of besifloxacin in dose-intense regimens are still unknown. Herein, a new quantification method was developed employing the widely accessible HPLC with fluorescence detection and applied to an ocular pharmacokinetic study with an intense regimen. Biosamples were pre-treated using protein precipitation. Chromatographic separation was achieved on a C18 column using mobile phase of 0.1\% trifluoroacetic acid and acetonitrile. To address the weak fluorescence issue of besifloxacin, effects of detection parameters, elution pattern, pH of mobile phase, and reconstitution solvents were investigated. The method was fully validated per US-FDA guidelines and demonstrated precision (\&lt;13\%), accuracy (91-112\%), lower limit of quantification (5\&nbsp;ng/mL), linearity over clinically relevant concentrations (R2\&nbsp;\&gt;\&nbsp;0.999), matrix-effects (93-105\%), recoveries (95-106\%), and excellent selectivity. The method showed agreement with agar disk diffusion assays for in vitro screening and comparable in vivo performance to LC-MS/MS (Deming Regression, y\&nbsp;=\&nbsp;1.010x\&nbsp;+\&nbsp;0.123, r\&nbsp;=\&nbsp;0.997; Bland-Altman analysis, mean difference was -6.3\%; n\&nbsp;=\&nbsp;21). Pharmacokinetic parameters suggested superior surface-retentive properties of besifloxacin. Maximum concentrations were 1412\&nbsp;{\textpm}\&nbsp;1910 and 0.15\&nbsp;{\textpm}\&nbsp;0.12\&nbsp;μg/mL; area under the curve was 1,637 and 1.08\&nbsp;{\textmu}g{\textperiodcentered}h/g; and half-life was 4.9 and 4.1\&nbsp;h; and pharmacokinetic-to-pharmacodynamic ratios were\&nbsp;>=\&nbsp;409 and\&nbsp;<=\&nbsp;17.8 against ocular pathogens in tears and aqueous humor, respectively. This readily available method is sensitive for biosamples and practical for routine use, facilitating besifloxacin therapy development.},
	issn = {1873-376X},
	doi = {10.1016/j.jchromb.2021.123010},
	author = {Kuang, Liangju and Ross, Amy E and Kanu, Levi N and Romanowski, Eric G and Kowalski, Regis P and Kohane, Daniel S and Ciolino, Joseph B}
}
@article {1598044,
	title = {Glaucoma and mortality risk: findings from a prospective population-based study},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Jun 03},
	pages = {11771},
	abstract = {Glaucoma is a neurodegenerative disease with a structural change of the optic nerve head, leading to visual field defects and ultimately blindness. It has been proposed that glaucoma is associated with increased mortality, but previous studies had methodological limitations (selective study samples, lack of data on potential confounders, self-reported or secondary data on glaucoma diagnoses). We evaluated the association between diagnosed glaucoma and mortality in the population-based National Health and Nutrition Examination Survey (NHANES), a representative health survey in the United States. The survey cycles 2005-2006 and 2007-2008 included an extensive ophthalmic examination with fundus photography, which were used to derive standardized glaucoma diagnoses. Risk of all-cause mortality was assessed with multivariable Cox proportional hazards regression models accounting for the complex survey design of NHANES. Time to death was calculated from the examination date to date of death or December 31, 2015 whichever came first. 5385 participants (52.5\% women) were eligible, of which 138 had glaucoma at baseline, and 833 died during follow-up. Participants with glaucoma were more likely to be older than those without glaucoma (mean age 69.9 vs. 56.0\&nbsp;years). Mean follow-up time was 8.4\&nbsp;years for participants with glaucoma, and 8.6\&nbsp;years for participants without glaucoma. Glaucoma was associated with increased mortality in an unadjusted Cox regression model (hazard ratio 2.06, 95\% confidence interval 1.16 to 3.66), but the association was no longer statistically significant after adjusting for age and sex (hazard ratio 0.74, 95\% confidence interval 0.46 to 1.17). Additional adjustment for a range of potential confounders did not significantly change the results. In this representative population-based study, we found no evidence of increased mortality risk in glaucoma patients.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-91194-3},
	author = {K{\"u}hn, Tilman and Rohrmann, Sabine and Karavasiloglou, Nena and Friedman, David S and Cassidy, Aedin and B{\"a}rnighausen, Till and Schuster, Alexander K and Nickels, Stefan}
}
@article {1632291,
	title = {Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study},
	journal = {Ophthalmology},
	volume = {129},
	number = {6},
	year = {2022},
	month = {2022 06},
	pages = {708-718},
	abstract = {PURPOSE: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). DESIGN: Multicenter, observational study. PARTICIPANTS: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n\&nbsp;= 523) or extracted from publicly available datasets from previously reported literature (n\&nbsp;= 384). METHODS: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. MAIN OUTCOME MEASURES: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA). RESULTS: The most common genetic etiology for typical FH in our cohort was albinism (67.5\%), followed by PAX6 (21.8\%), SLC38A8 (6.8\%), and FRMD7 (3.5\%) variants. AHR variants were rare (0.4\%). Atypical FH was seen in 67.4\% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P \&lt; 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square\&nbsp;= 60.4, P \&lt; 0.0001). All SLC38A8 cases were PRS- (P\&nbsp;= 0.003), whereas all FRMD7 cases were PRS+ (P \&lt; 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square\&nbsp;= 31.4, P \&lt; 0.0001) and VA (P\&nbsp;= 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P \&lt; 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. CONCLUSIONS: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to\&nbsp;demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH\&nbsp;and have significant prognostic and diagnostic value.},
	keywords = {Albinism, Albinism, Ocular, Albinism, Oculocutaneous, Color Vision Defects, Cytoskeletal Proteins, Fovea Centralis, Humans, Membrane Proteins, Vision Disorders},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.02.010},
	author = {Kuht, Helen J and Maconachie, Gail D E and Han, Jinu and Kessel, Line and van Genderen, Maria M and McLean, Rebecca J and Hisaund, Michael and Tu, Zhanhan and Hertle, Richard W and Gronskov, Karen and Bai, Dayong and Wei, Aihua and Li, Wei and Jiao, Yonghong and Smirnov, Vasily and Choi, Jae-Hwan and Tobin, Martin D and Sheth, Viral and Purohit, Ravi and Dawar, Basu and Girach, Ayesha and Strul, Sasha and May, Laura and Chen, Fred K and Heath Jeffery, Rachael C and Aamir, Abdullah and Sano, Ronaldo and Jin, Jing and Brooks, Brian P and Kohl, Susanne and Arveiler, Benoit and Montoliu, Lluis and Engle, Elizabeth C and Proudlock, Frank A and Nishad, Garima and Pani, Prateek and Varma, Girish and Gottlob, Irene and Thomas, Mervyn G}
}
@article {1319470,
	title = {Traumatic corneal perforation with exteriorisation of Ahmed glaucoma valve tube},
	journal = {BMJ Case Rep},
	volume = {2018},
	year = {2018},
	month = {2018 Jun 11},
	abstract = {We report a rare case of traumatic corneal perforation with Ahmed glaucoma valve (AGV) tube. A 5-year-old female child, diagnosed with refractory glaucoma, had undergone AGV implantation, presented with the posterior migration of AGV tube after trauma to the eye. The detailed ocular history, ophthalmic findings, clinical course and surgical management are discussed.},
	issn = {1757-790X},
	doi = {10.1136/bcr-2018-225181},
	author = {Kumar, Suresh and Ichhpujani, Parul and Thakur, Sahil and Singh, Rohan Bir}
}
@article {1651357,
	title = {Comparison of visual SLAM and IMU in tracking head movement outdoors},
	journal = {Behav Res Methods},
	year = {2022},
	author = {Kumar, A, A and Pundlik, S and Peli, E and Luo, G}
}
@article {1466907,
	title = {Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases},
	journal = {Neurology (ECronicon)},
	volume = {11},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {864-873},
	abstract = {Neurodegenerative diseases demonstrate the progressive decline of brain functions resulting in a significant deterioration in the quality of patient{\textquoteright}s life. With increasing life expectancy, there has been a significant increase in the incidence of these diseases. Neurodegenerative diseases like Alzheimer{\textquoteright}s, Parkinson{\textquoteright}s, and Amyotrophic lateral sclerosis are devastating and afflicts a large world population. Eye, given the similar neural and vascular similarity to the brain, demonstrates many pathological hallmarks of some of these neurological diseases. Moreover, these diseases create an economic and social burden to society. Despite tremendous efforts made in the drug discovery, there is no cure for these fatal diseases. Thus, there is an unmet need to understand cellular and molecular pathophysiology of these diseases. All these diseases demonstrate damage to a large number of seemingly disparate cellular processes and functions such as Ca homeostasis, lipid metabolism, axonal transport, unfolded protein response, autophagy and inflammatory responses. Mitochondria are closely associated with Endoplasmic reticulum (ER) and ER-mitochondrial cross-talk regulates many of these cellular processes and functions damaged in neurodegenerative and eye diseases. Several studies have implicated the disruption of ER-mitochondria contacts in these diseases. This review is aimed at understanding and summarizing the role of ER-mitochondria interacting proteins in major neurodegenerative and eye diseases studied so far.},
	author = {Kumar, Varun}
}
@article {1789171,
	title = {Estrogen genotoxicity causes preferential development of Fuchs endothelial corneal dystrophy in females},
	journal = {Redox Biol},
	volume = {69},
	year = {2024},
	month = {2024 Feb},
	pages = {102986},
	abstract = {Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, age-related, female-predominant disorder characterized by loss of post-mitotic corneal endothelial cells (CEnCs). Ultraviolet-A (UVA) light has been shown to recapitulate the morphological and molecular changes seen in FECD to a greater extent in females than males, by triggering CYP1B1 upregulation in females. Herein, we investigated the mechanism of greater CEnC susceptibility to UVA in females by studying estrogen metabolism in response to UVA in the cornea. Loss of NAD(P)H quinone oxidoreductase 1 (NQO1) resulted in increased production of estrogen metabolites and mitochondrial-DNA adducts, with a higher CEnC loss in Nqo1-/- female compared to wild-type male and female mice. The CYP1B1 inhibitors, trans-2,3{\textquoteright},4,5{\textquoteright}-tetramethoxystilbene (TMS) and berberine, rescued CEnC loss. Injection of wild-type male mice with estrogen (E2; 17β-estradiol) increased CEnC loss, followed by increased production of estrogen metabolites and mitochondrial DNA (mtDNA) damage, not seen in E2-treated Cyp1b1-/-male mice. This study demonstrates that the endo-degenerative phenotype is driven by estrogen metabolite-dependent CEnC loss that is exacerbated in the absence of NQO1; thus, explaining the mechanism accounting for the higher incidence of FECD in females. The mitigation of estrogen-adduct production by CYP1B1 inhibitors could serve as a novel therapeutic strategy for FECD.},
	keywords = {Animals, Cornea, DNA Damage, DNA, Mitochondrial, Endothelial Cells, Estrogens, Female, Fuchs{\textquoteright} Endothelial Dystrophy, Male, Mice},
	issn = {2213-2317},
	doi = {10.1016/j.redox.2023.102986},
	author = {Kumar, Varun and Deshpande, Neha and Parekh, Mohit and Wong, Raymond and Ashraf, Shazia and Zahid, Muhammad and Hui, Hanna and Miall, Annie and Kimpton, Sylvie and Price, Marianne O and Price, Francis W and Gonzalez, Frank J and Rogan, Eleanor and Jurkunas, Ula V}
}
@article {1364502,
	title = {Oral acetazolamide after Boston keratoprosthesis in Stevens-Johnson syndrome},
	journal = {BMC Res Notes},
	volume = {5},
	year = {2012},
	month = {2012 Apr 30},
	pages = {205},
	abstract = {BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare but severe and sometimes fatal condition associated with exposure to medications; sulfamethoxazole is among the most common causes. We sought to address the safety of acetazolamide, a chemically related compound, in patients with prior SJS/TEN and glaucoma. A retrospective case series is described of patients at the Massachusetts Eye and Ear Infirmary who underwent keratoprosthesis surgery for corneal blindness from SJS/TEN, and later required oral acetazolamide for elevated intraocular pressure. FINDINGS: Over the last 10 years, 17 patients with SJS/TEN received a Boston keratoprosthesis. Of these, 11 developed elevated intraocular pressure that required administration of oral acetazolamide. One of 11 developed a mild allergic reaction, but no patient experienced a recurrence of SJS/TEN or any severe adverse reaction. CONCLUSION: Although an increase in the rate of recurrent SJS/TEN due to oral acetazolamide would not necessarily be apparent after treating only 11 patients, in our series, acetazolamide administration was well tolerated without serious sequela.},
	keywords = {Acetazolamide, Administration, Oral, Adolescent, Adult, Boston, Carbonic Anhydrase Inhibitors, Cornea, Female, Glaucoma, Humans, Intraocular Pressure, Male, Middle Aged, Polymethyl Methacrylate, Prostheses and Implants, Retrospective Studies, Stevens-Johnson Syndrome, Titanium},
	issn = {1756-0500},
	doi = {10.1186/1756-0500-5-205},
	author = {Kumar, Radhika and Dohlman, Claes H and Chodosh, James}
}
@article {1538314,
	title = {Dual Specific Phosphatase 14 Deletion Rescues Retinal Ganglion Cells and Optic Nerve Axons after Experimental Anterior Ischemic Optic Neuropathy},
	journal = {Curr Eye Res},
	volume = {46},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {710-718},
	abstract = {PURPOSE: Understanding molecular changes is essential for designing effective treatments for nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults older than 50\&nbsp;years. We investigated changes in the mitogen-activated protein kinase (MAPK) pathway after experimental AION and focused on dual specificity phosphatase 14 (Dusp14), an atypical MAPK phosphatase that is downstream of Kr{\"u}ppel-like transcription factor (KLF) 9-mediated inhibition of retinal ganglion cell (RGC) survival and axonal regeneration. MATERIALS AND METHODS: We induced severe AION in a photochemical thrombosis model in adult C57BL/6 wild-type and Dusp14 knockout mice. For comparison, some studies were performed using an optic nerve crush model. We assessed changes in MAPK pathway molecules using Western blot and immunohistochemistry, measured retinal thickness using optical coherence tomography (OCT), and quantified RGCs and axons using histologic methods. RESULTS: Three days after severe AION, there was no change in the retinal protein levels of MAPK ERK1/2, phosphorylated-ERK1/2 (pERK1/2), downstream effector Elk-1 and phosphatase Dusp14 on Western blot. Western blot analysis of purified RGCs after a more severe model using optic nerve crush also showed no change in Dusp14 protein expression. Because of the known importance of the Dusp14 and MAPK pathway in RGCs, we examined changes after AION in Dusp14 knockout mice. Three days after AION, Dusp14 knockout mice had significantly increased pERK1/2+, Brn3A+ RGCs on immunohistochemistry. Three weeks after AION, Dusp14 knockout mice had significantly greater preservation of retinal thickness, increased number of Brn3A+ RGCs on whole mount preparation, and increased number of optic nerve axons compared with wild-type mice. CONCLUSIONS: Genetic deletion of Dusp14, a MAPK phosphatase important in KFL9-mediated inhibition of RGC survival, led to increased activation of MAPK ERK1/2 and greater RGC and axonal survival after experimental AION. Inhibiting Dusp14 or activating the MAPK pathway should be examined further as a potential therapeutic approach to treatment of AION. Abbreviations: AION: anterior ischemic optic neuropathy; Dusp14: dual specific phosphatase 14; ERK1/2: extracellular signal-regulated kinases 1/2; Elk-1: ETS Like-1 protein; GCC: ganglion cell complex; GCL: ganglion cell layer; inner nuclear layer; KO: knockout; MAPK: mitogen-activated phosphokinase; OCT: optical coherence tomography; RGC: retinal ganglion cell; RNFL: retinal nerve fiber layer.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2020.1826976},
	author = {Kumar, Varun and Ali Shariati, Mohammad and Mesentier-Louro, Louise and Jinsook Oh, Angela and Russano, Kristina and Goldberg, Jeffrey L and Liao, Yaping Joyce}
}
@article {635031,
	title = {AMPK-Activated Protein Kinase Suppresses Ccr2 Expression by Inhibiting the NF-κB Pathway in RAW264.7 Macrophages.},
	journal = {PLoS One},
	volume = {11},
	number = {1},
	year = {2016},
	month = {2016},
	pages = {e0147279},
	abstract = {C-C chemokine receptor 2 (Ccr2) is a key pro-inflammatory marker of classic (M1) macrophage activation. Although Ccr2 is known to be expressed both constitutively and inductively, the full regulatory mechanism of its expression remains unclear. AMP-activated protein kinase (AMPK) is not only a master regulator of energy homeostasis but also a central regulator of inflammation. In this study, we sought to assess AMPK{\textquoteright}s role in regulating RAW264.7 macrophage Ccr2 protein levels in resting (M0) or LPS-induced M1 states. In both M0 and M1 RAW264.7 macrophages, knockdown of the AMPKα1 subunit by siRNA led to increased Ccr2 levels whereas pharmacologic (A769662) activation of AMPK, attenuated LPS-induced increases in Ccr2 expression in an AMPK dependent fashion. The increases in Ccr2 levels by AMPK downregulation were partially reversed by NF-κB inhibition whereas TNF-a inhibition had minimal effects. Our results indicate that AMPK is a negative regulator of Ccr2 expression in RAW264.7 macrophages, and that the mechanism of action of AMPK inhibition of Ccr2 is mediated, in part, through the NF-κB pathway.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0147279},
	author = {Kumase, Fumiaki and Takeuchi, Kimio and Morizane, Yuki and Suzuki, Jun and Matsumoto, Hidetaka and Kataoka, Keiko and Al-Moujahed, Ahmad and Maidana, Daniel E and Miller, Joan W and Vavvas, Demetrios G}
}
@article {603906,
	title = {Decellularized retinal matrix: natural platforms for human retinal progenitor cell culture.},
	journal = {Acta Biomater},
	year = {2015},
	month = {2015 Nov 24},
	abstract = {Tissue decellularization strategies have enabled engineering of scaffolds that preserve native extracellular matrix (ECM) structure and composition. In this study, we developed decellularized retina (decell-retina) thin films. We hypothesized that these films, mimicking the retina niche, would promote human retinal progenitor cell (hRPC) attachment, proliferation and differentiation. Retinas isolated from bovine eyes were decellularized using 1\% w/v sodium dodecyl sulfate (SDS) and pepsin digested. The resulting decell-retina was biochemically assayed for composition and cast dried to develop thin films. Attachment, viability, morphology, proliferation and gene expression of hRPC cultured on the films were studied in vitro. Biochemical analyses of decell-retina compared to native retina indicated the bulk of DNA (94\%) was removed, while the majority of sulfated GAGs (55\%), collagen (83\%), hyaluronic acid (87\%), and key growth factors were retained. The decell-retina films supported hRPC attachment and growth, with cell number increasing 1.5-fold over a week. RT-PCR analysis revealed hRPC expression of rhodopsin, rod outer membrane, neural retina-specific leucine zipper neural and cone-rod homeobox gene on decell-retina films, indicating photoreceptor development. In conclusion, novel decell-retina films show promise as potential substrates for culture and/or transplantation of retinal progenitor cells to treat retinal degenerative disorders.},
	issn = {1878-7568},
	doi = {10.1016/j.actbio.2015.11.028},
	author = {Kundu, Joydip and Michaelson, Andrew and Talbot, Kristen and Baranov, Petr and Young, Michael J and Carrier, Rebecca L}
}
@article {1629450,
	title = {Intraoperative OCT Angiography in Children with Incontinentia Pigmenti},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {4},
	year = {2022},
	month = {2022 Apr},
	pages = {330-332},
	keywords = {Child, Fluorescein Angiography, Humans, Incontinentia Pigmenti, Retinal Vessels, Tomography, Optical Coherence},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.01.001},
	author = {Kunkler, Anne L and Patel, Nimesh A and Russell, Jonathan F and Fan, Kenneth C and Al-Khersan, Hasenin and Iyer, Prashanth G and Acon, Dhariana and Negron, Catherin I and Yannuzzi, Nicolas A and Berrocal, Audina M}
}
@article {1817236,
	title = {Advanced Corneal Imaging in Keratoconus: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {131},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {107-121},
	abstract = {PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus.

METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65\% to 100\%. The majority of studies and parameters had sensitivities greater than 90\%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90\%.

CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Cornea, Corneal Pachymetry, Corneal Topography, Humans, Keratoconus, Ophthalmology, ROC Curve, Tomography},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.07.030},
	author = {Kuo, Anthony N and Cortina, Maria S and Greiner, Mark A and Li, Jennifer Y and Miller, Darby D and Shtein, Roni M and Veldman, Peter B and Yin, Jia and Kim, Stephen J and Shen, Joanne F}
}
@article {1655725,
	title = {Murine endothelial serine palmitoyltransferase 1 (SPTLC1) is required for vascular development and systemic sphingolipid homeostasis},
	journal = {Elife},
	volume = {11},
	year = {2022},
	month = {2022 Oct 05},
	abstract = {Serine palmitoyl transferase (SPT), the rate-limiting enzyme in the de novo synthesis of sphingolipids (SL), is needed for embryonic development, physiological homeostasis, and response to stress. The functions of de novo SL synthesis in vascular endothelial cells (EC), which line the entire circulatory system, are not well understood. Here, we show that the de novo SL synthesis in EC not only regulates vascular development but also maintains circulatory and peripheral organ SL levels. Mice with an endothelial-specific gene knockout of SPTLC1 (Sptlc1 ECKO), an essential subunit of the SPT complex, exhibited reduced EC proliferation and tip/stalk cell differentiation, resulting in delayed retinal vascular development. In addition, Sptlc1 ECKO mice had reduced retinal neovascularization in the oxygen-induced retinopathy model. Mechanistic studies suggest that EC SL produced from the de novo pathway are needed for lipid raft formation and efficient VEGF signaling. Post-natal deletion of the EC Sptlc1 also showed rapid reduction of several SL metabolites in plasma, red blood cells, and peripheral organs (lung and liver) but not in the retina, part of the central nervous system (CNS). In the liver, EC de novo SL synthesis was important for acetaminophen-induced rapid ceramide elevation and hepatotoxicity. These results suggest that EC-derived SL metabolites are in constant flux between the vasculature, circulatory elements, and parenchymal cells of non-CNS organs. Taken together, our data point to the central role of the endothelial SL biosynthesis in maintaining vascular development, neovascular proliferation, non-CNS tissue metabolic homeostasis, and hepatocyte response to stress.},
	keywords = {Acetaminophen, Animals, Ceramides, Endothelial Cells, Homeostasis, Mice, Oxygen, Serine, Serine C-Palmitoyltransferase, Sphingolipids, Vascular Endothelial Growth Factor A},
	issn = {2050-084X},
	doi = {10.7554/eLife.78861},
	author = {Kuo, Andrew and Checa, Antonio and Niaudet, Colin and Jung, Bongnam and Fu, Zhongjie and Wheelock, Craig E and Sasha A Singh and Aikawa, Masanori and Smith, Lois E and Proia, Richard L and Hla, Timothy}
}
@article {1364503,
	title = {Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study},
	journal = {Eye (Lond)},
	volume = {26},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {126-32},
	abstract = {PURPOSE: To study sub-basal corneal nerve alterations in patients with acute Acanthamoeba keratitis (AK) and fungal keratitis (FK), using laser in vivo confocal microscopy (IVCM). METHODS: A retrospective analysis of IVCM (Heidelberg Retina Tomograph 3/Rostock Cornea Module) images of 10 AK corneas and 4 FK corneas was performed, and the results compared with those of 10 normal and 12 acute herpetic keratitis (HK) corneas. Sub-basal corneal nerves were analyzed with respect to total number of nerves, main nerve trunks, branching pattern and total length of nerves per image, as well as tortuosity. For each variable, results for three frames were averaged and analyzed using analysis of variance. RESULTS: Total corneal nerve length was significantly (P \&lt; 0.0001) reduced in patients with AK (193.4 {\textpm} 124.5 μm) and FK (268.6 {\textpm} 257.4 μm) when compared with normal controls (3811.84 {\textpm} 911.4 μm). Total nerve counts in patients with AK (3.9 {\textpm} 1.2) and FK (3.6 {\textpm} 3.2) were significantly (P \&lt; 0.0001) decreased in comparison with normal controls (24.7 {\textpm} 5.5). The number of main nerve trunks and nerve branching was found to be significantly lower in AK and FK corneas, when compared with controls. There was a statistically significant decrease in the above parameters when compared with HK controls. CONCLUSIONS: The sub-basal corneal nerve plexus is significantly diminished in eyes with AK and FK, as demonstrated by IVCM. These results are more profound than previously reported findings of a diminished nerve plexus in HK.},
	keywords = {Acanthamoeba Keratitis, Adult, Analysis of Variance, Cornea, Corneal Ulcer, Eye Infections, Fungal, Female, Humans, Keratitis, Male, Microscopy, Confocal, Middle Aged, Nerve Fibers, Ophthalmic Nerve, Prognosis, Retrospective Studies},
	issn = {1476-5454},
	doi = {10.1038/eye.2011.270},
	author = {Kurbanyan, K and Hoesl, L M and Schrems, W A and Hamrah, P}
}
@article {1363134,
	title = {Neutrophils express oncomodulin and promote optic nerve regeneration},
	journal = {J Neurosci},
	volume = {33},
	number = {37},
	year = {2013},
	month = {2013 Sep 11},
	pages = {14816-24},
	abstract = {Although neurons are normally unable to regenerate their axons after injury to the CNS, this situation can be partially reversed by activating the innate immune system. In a widely studied instance of this phenomenon, proinflammatory agents have been shown to cause retinal ganglion cells, the projection neurons of the eye, to regenerate lengthy axons through the injured optic nerve. However, the role of different molecules and cell populations in mediating this phenomenon remains unclear. We show here that neutrophils, the first responders of the innate immune system, play a central role in inflammation-induced regeneration. Numerous neutrophils enter the mouse eye within a few hours of inducing an inflammatory reaction and express high levels of the atypical growth factor oncomodulin (Ocm). Immunodepletion of neutrophils diminished Ocm levels in the eye without altering levels of CNTF, leukemia inhibitory factor, or IL-6, and suppressed the proregenerative effects of inflammation. A peptide antagonist of Ocm suppressed regeneration as effectively as neutrophil depletion. Macrophages enter the eye later in the inflammatory process but appear to be insufficient to stimulate extensive regeneration in the absence of neutrophils. These data provide the first evidence that neutrophils are a major source of Ocm and can promote axon regeneration in the CNS.},
	keywords = {Animals, Antigens, CD, Calcium-Binding Proteins, Cells, Cultured, Ciliary Neurotrophic Factor, Intercellular Signaling Peptides and Proteins, Interleukin-6, Leukemia Inhibitory Factor, Male, Mice, Mice, Inbred C57BL, Nerve Crush, Nerve Regeneration, Neutrophils, Optic Nerve Diseases, Receptors, Cell Surface, Retina, Retinal Ganglion Cells, Stilbamidines, Visual Pathways},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.5511-12.2013},
	author = {Kurimoto, Takuji and Yin, Yuqin and Habboub, Ghaith and Gilbert, Hui-Ya and Li, Yiqing and Nakao, Shintaro and Hafezi-Moghadam, Ali and Benowitz, Larry I}
}
@article {1748486,
	title = {An Adjustable Magnetic Levator Prosthesis for Customizable Eyelid Re-Animation in Severe Blepharoptosis: Design and Proof-of-Concept},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {8},
	year = {2023},
	month = {2023 Aug 01},
	pages = {11},
	abstract = {PURPOSE: Blepharoptosis is a common oculoplastic condition causing incomplete opening of the upper eyelid. Surgical approaches, the mainstay for correction, often fail to improve blink function. The purpose of this study was to develop a nonsurgical treatment option for severe ptosis that allows blink re-animation. METHODS: Magnetic force required to perform blink re-animation was characterized by evaluation of eye-opening and closing using inter-palpebral fissure (IPF) outcomes with various combinations of eyelid array and box magnets. Optimal size of the spectacle magnet that achieved forces required for optimal blink dynamics was selected using simulation. The adjustable magnetic levator prosthesis (aMLP) included an eyelid array magnet and an adjustable rotating spectacle magnet that allowed change in the magnetic direction, thus changing the net magnetic interactive force between the magnets. The clinical feasibility of aMLP in improving eye opening without limiting eye closing was evaluated in patients with ptosis through a proof-of-concept study using IPF and comfort outcomes. RESULTS: Optimal eye opening and closing was achieved by a magnet-array combination providing 45 grams of surface force (gF) in the tested ptosis population. The aMLP was able to modulate eye opening and closing with change in rotation of the spectacle magnet in two patients with ptotis. The best fitting of an aMLP improved IPF opening without limiting eye closing and with good comfort reported. CONCLUSIONS: Preliminary results suggest that the an aMLP can correct ptosis without adversely affecting blink function. Further evaluation in a larger patient population is warranted. TRANSLATIONAL RELEVANCE: A nonsurgical, proof of concept, adjustable magnetic treatment option for blink re-animation in patients with severe ptosis is presented.},
	keywords = {Blepharoptosis, Eyelids, Humans, Magnetic Phenomena, Prostheses and Implants},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.8.11},
	author = {Kurukuti, Nish Mohith and Nadeau, Melanie and Paschalis, Eleftherios I and Houston, Kevin E}
}
@article {1732506,
	title = {Oxidative Stress and Antioxidants in Age-Related Macular Degeneration},
	journal = {Antioxidants (Basel)},
	volume = {12},
	number = {7},
	year = {2023},
	month = {2023 Jul 03},
	abstract = {Oxidative stress plays a crucial role in aging-related eye diseases, including age-related macular degeneration (AMD), cataracts, and glaucoma. With age, antioxidant reparative capacity decreases, and excess levels of reactive oxygen species produce oxidative damage in many ocular cell types underling age-related pathologies. In AMD, loss of central vision in the elderly is caused primarily by retinal pigment epithelium (RPE) dysfunction and degeneration and/or choroidal neovascularization that trigger malfunction and loss of photo-sensing photoreceptor cells. Along with various genetic and environmental factors that contribute to AMD, aging and age-related oxidative damage have critical involvement in AMD pathogenesis. To this end, dietary intake of antioxidants is a proven way to scavenge free radicals and to prevent or slow AMD progression. This review focuses on AMD and highlights the pathogenic role of oxidative stress in AMD from both clinical and experimental studies. The beneficial roles of antioxidants and dietary micronutrients in AMD are also summarized.},
	issn = {2076-3921},
	doi = {10.3390/antiox12071379},
	author = {Kushwah, Neetu and Bora, Kiran and Maurya, Meenakshi and Pavlovich, Madeline C and Chen, Jing}
}
@article {1664966,
	title = {Corneal Adverse Events Associated with SARS-CoV-2/COVID-19 Vaccination: A Systematic Review},
	journal = {Vaccines (Basel)},
	volume = {11},
	number = {1},
	year = {2023},
	month = {2023 Jan 12},
	abstract = {Vaccines against coronavirus disease 2019 (COVID-19) have played an important global role in reducing morbidity and mortality from COVID-19 infection. While the benefits of vaccination greatly outweigh the risks, adverse events do occur. Non-ocular adverse effects of the vaccines have been well-documented, but descriptions of ophthalmic effects remain limited. This systematic review aims to provide an overview of reported cases of corneal adverse events after receiving vaccination against COVID-19 and to compile existing clinical data to bring attention to these phenomena. Our review discusses corneal graft rejection, including proposed mechanisms, herpetic keratitis, and other reported corneal complications. Ophthalmologists and primary care physicians should be aware of such possible associations.},
	issn = {2076-393X},
	doi = {10.3390/vaccines11010166},
	author = {Kuziez, Lana and Eleiwa, Taher K and Chauhan, Muhammad Z and Sallam, Ahmed B and Elhusseiny, Abdelrahman M and Saeed, Hajirah N}
}
@article {1632314,
	title = {Alcohol, intraocular pressure and open-angle glaucoma: A systematic review and meta-analysis},
	journal = {Ophthalmology},
	year = {2022},
	author = {Stuart KV and Madjedi K and Luben RN and Chua SYL and Warwick AN and Chia M and Pasquale LR and Wiggs JL and Kang JH and Foster PJ and Khawaja AP and Modifiable Risk Factors for Glaucoma Collaboration}
}
@article {1638572,
	title = {Relationship between Atopic Disease and Acute Ocular and Systemic Outcomes in Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis},
	journal = {Ocul Immunol Inflamm},
	volume = {31},
	number = {5},
	year = {2023},
	month = {2023 Jul},
	pages = {900-904},
	abstract = {OBJECTIVE: To describe the relationship between history of atopic disease on systemic and ocular manifestations of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). METHODS: Retrospective chart review of patients with SJS/TEN patients. Those with and without prior atopic diagnosis were compared. RESULTS: In total, 200 patients with SJS/TEN were identified. A total of 23 patients also had an atopic diagnosis. Four, 10, and 18 had atopic dermatitis, allergic rhinitis, and asthma respectively. Acute ocular severity was significantly worse in the atopic cohort. No significant differences in overall systemic severity of SJS or mortality were found between the atopic and non-atopic cohorts. Compared to our hospital system{\textquoteright}s general population, prevalence of an atopic diagnosis was significantly higher in those with SJS/TEN. CONCLUSION: Patients with a history of an atopic diagnosis appear to have more significant acute ocular involvement during their SJS/TEN hospitalization. Atopic conditions appear to occur more frequently in the SJS/TEN population compared to the general population.},
	keywords = {Dermatitis, Atopic, Eye, Eye Diseases, Humans, Retrospective Studies, Stevens-Johnson Syndrome},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2061520},
	author = {Kwan, James and Ahmed, Harris and Ponsetto, Momoko K and Succar, Tony and Chodosh, James and Saeed, Hajirah N}
}
@article {1363135,
	title = {Rapid and persistent adaptability of human oculomotor control in response to simulated central vision loss},
	journal = {Curr Biol},
	volume = {23},
	number = {17},
	year = {2013},
	month = {2013 Sep 09},
	pages = {1663-9},
	abstract = {The central region of the human retina, the fovea, provides high-acuity vision. The oculomotor system continually brings targets of interest into the fovea via ballistic eye movements (saccades). Thus, the fovea serves both as the locus for fixations and as the oculomotor reference for saccades. This highly automated process of foveation is functionally critical to vision and is observed from infancy. How would the oculomotor system adjust to a loss of foveal vision (central scotoma)? Clinical observations of patients with central vision loss suggest a lengthy adjustment period, but the nature and dynamics of this adjustment remain unclear. Here, we demonstrate that the oculomotor system can spontaneously and rapidly adopt a peripheral locus for fixation and can rereference saccades to this locus in normally sighted individuals whose central vision is blocked by an artificial scotoma. Once developed, the fixation locus is retained over weeks in the absence of the simulated scotoma. Our data reveal a basic guiding principle of the oculomotor system that prefers control simplicity over optimality. We demonstrate the importance of a visible scotoma on the speed of the adjustment and suggest a possible rehabilitation regimen for patients with central vision loss.},
	keywords = {Adaptation, Physiological, Humans, Oculomotor Muscles, Saccades, Vision Disorders},
	issn = {1879-0445},
	doi = {10.1016/j.cub.2013.06.056},
	author = {Kwon, MiYoung and Nandy, Anirvan S and Tjan, Bosco S}
}
@article {382246,
	title = {Assessing binocular interaction in amblyopia and its clinical feasibility},
	journal = {PLoS One},
	volume = {9},
	number = {6},
	year = {2014},
	month = {2014},
	pages = {e100156},
	abstract = {PURPOSE: To measure binocular interaction in amblyopes using a rapid and patient-friendly computer-based method, and to test the feasibility of the assessment in the clinic. METHODS: Binocular interaction was assessed in subjects with strabismic amblyopia (n = 7), anisometropic amblyopia (n = 6), strabismus without amblyopia (n = 15) and normal vision (n = 40). Binocular interaction was measured with a dichoptic phase matching task in which subjects matched the position of a binocular probe to the cyclopean perceived phase of a dichoptic pair of gratings whose contrast ratios were systematically varied. The resulting effective contrast ratio of the weak eye was taken as an indicator of interocular imbalance. Testing was performed in an ophthalmology clinic under 8 mins. We examined the relationships between our binocular interaction measure and standard clinical measures indicating abnormal binocularity such as interocular acuity difference and stereoacuity. The test-retest reliability of the testing method was also evaluated. RESULTS: Compared to normally-sighted controls, amblyopes exhibited significantly reduced effective contrast (\~{}20\%) of the weak eye, suggesting a higher contrast requirement for the amblyopic eye compared to the fellow eye. We found that the effective contrast ratio of the weak eye covaried with standard clincal measures of binocular vision. Our results showed that there was a high correlation between the 1st and 2nd measurements (r = 0.94, p\&lt;0.001) but without any significant bias between the two. CONCLUSIONS: Our findings demonstrate that abnormal binocular interaction can be reliably captured by measuring the effective contrast ratio of the weak eye and quantitative assessment of binocular interaction is a quick and simple test that can be performed in the clinic. We believe that reliable and timely assessment of deficits in a binocular interaction may improve detection and treatment of amblyopia.},
	keywords = {Adolescent, Adult, Amblyopia, Case-Control Studies, Child, Child, Preschool, Female, Humans, Male, Reproducibility of Results, Vision Tests, Vision, Binocular, Visual Acuity, Young Adult},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0100156},
	author = {Kwon, MiYoung and Lu, Zhong-Lin and Miller, Alexandra and Kazlas, Melanie and Hunter, David G and Bex, Peter J}
}
@article {314151,
	title = {Radial-tangential anisotropy of crowding in the early visual areas},
	journal = {J Neurophysiol},
	volume = {112},
	number = {10},
	year = {2014},
	month = {2014 Nov 15},
	pages = {2413-22},
	abstract = {Crowding, the inability to recognize an individual object in clutter (Bouma H. Nature 226: 177-178, 1970), is considered a major impediment to object recognition in peripheral vision. Despite its significance, the cortical loci of crowding are not well understood. In particular, the role of the primary visual cortex (V1) remains unclear. Here we utilize a diagnostic feature of crowding to identify the earliest cortical locus of crowding. Controlling for other factors, radially arranged flankers induce more crowding than tangentially arranged ones (Toet A, Levi DM. Vision Res 32: 1349-1357, 1992). We used functional magnetic resonance imaging (fMRI) to measure the change in mean blood oxygenation level-dependent (BOLD) response due to the addition of a middle letter between a pair of radially or tangentially arranged flankers. Consistent with the previous finding that crowding is associated with a reduced BOLD response [Millin R, Arman AC, Chung ST, Tjan BS. Cereb Cortex (July 5, 2013). doi:10.1093/cercor/bht159], we found that the BOLD signal evoked by the middle letter depended on the arrangement of the flankers: less BOLD response was associated with adding the middle letter between radially arranged flankers compared with adding it between tangentially arranged flankers. This anisotropy in BOLD response was present as early as V1 and remained significant in downstream areas. The effect was observed while subjects{\textquoteright} attention was diverted away from the testing stimuli. Contrast detection threshold for the middle letter was unaffected by flanker arrangement, ruling out surround suppression of contrast response as a major factor in the observed BOLD anisotropy. Our findings support the view that V1 contributes to crowding.},
	keywords = {Anisotropy, Cerebrovascular Circulation, Female, Humans, Magnetic Resonance Imaging, Male, Oxygen, Pattern Recognition, Visual, Photic Stimulation, Psychophysics, Signal Detection, Psychological, Visual Cortex},
	issn = {1522-1598},
	doi = {10.1152/jn.00476.2014},
	author = {Kwon, MiYoung and Bao, Pinglei and Millin, Rachel and Tjan, Bosco S}
}
@article {1603863,
	title = {Visual function rather than visual acuity - Authors{\textquoteright} reply},
	journal = {Lancet Glob Health},
	volume = {9},
	number = {7},
	year = {2021},
	month = {2021 Jul},
	pages = {e914},
	issn = {2214-109X},
	doi = {10.1016/S2214-109X(21)00246-1},
	author = {Kyari, Fatima and Bourne, Rupert R A and Khaw, Peng T and Friedman, David S and Congdon, Nathan and Ramke, Jacqueline and Burton, Matthew J}
}
@article {1642388,
	title = {Global Current Practice Patterns for the Management of Central Retinal Artery Occlusion},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {5},
	year = {2022},
	pages = {429-31},
	author = {Thangamathesvaran L and Miller SC and Tsou B and Fliotsos MJ and Yonekawa Y and Chen A and Hoskin AK and Blanch RJ and Cavuoto K and Meeralakshmi P and Low R and Gardiner M and Alvin Liu TY and Agrawal R and Justin GA and Woreta FA and International Globe and Adnexal Trauma Epidemiology Study (IGATES)(18) group}
}
@article {397831,
	title = {A Genomic Virulence Reference Map of Enterococcus faecalis Reveals an Important Contribution of Phage03-Like Elements in Nosocomial Genetic Lineages to Pathogenicity in a Caenorhabditis elegans Infection Model.},
	journal = {Infect Immun},
	volume = {83},
	number = {5},
	year = {2015},
	month = {2015 May},
	pages = {2156-67},
	abstract = {In the present study, the commensal and pathogenic host-microbe interaction of Enterococcus faecalis was explored using a Caenorhabditis elegans model system. The virulence of 28 E. faecalis isolates representing 24 multilocus sequence types (MLSTs), including human commensal and clinical isolates as well as isolates from animals and of insect origin, was investigated using C. elegans strain glp-4 (bn2ts); sek-1 (km4). This revealed that 6 E. faecalis isolates behaved in a commensal manner with no nematocidal effect, while the remaining strains showed a time to 50\% lethality ranging from 47 to 120 h. Principal component analysis showed that the difference in nematocidal activity explained 94\% of the variance in the data. Assessment of known virulence traits revealed that gelatinase and cytolysin production accounted for 40.8\% and 36.5\% of the observed pathogenicity, respectively. However, coproduction of gelatinase and cytolysin did not increase virulence additively, accounting for 50.6\% of the pathogenicity and therefore indicating a significant (26.7\%) saturation effect. We employed a comparative genomic analysis approach using the 28 isolates comprising a collection of 82,356 annotated coding sequences (CDS) to identify 2,325 patterns of presence or absence among the investigated strains. Univariate statistical analysis of variance (ANOVA) established that individual patterns positively correlated (n = 61) with virulence. The patterns were investigated to identify potential new virulence traits, among which we found five patterns consisting of the phage03-like gene clusters. Strains harboring phage03 showed, on average, 17\% higher killing of C. elegans (P = 4.4e(-6)). The phage03 gene cluster was also present in gelatinase-and-cytolysin-negative strain E. faecalis JH2-2. Deletion of this phage element from the JH2-2 clinical strain rendered the mutant apathogenic in C. elegans, and a similar mutant of the nosocomial V583 isolate showed significantly attenuated virulence. Bioinformatics investigation indicated that, unlike other E. faecalis virulence traits, phage03-like elements were found at a higher frequency among nosocomial isolates. In conclusion, our report provides a valuable virulence map that explains enhancement in E. faecalis virulence and contributes to a deeper comprehension of the genetic mechanism leading to the transition from commensalism to a pathogenic lifestyle.},
	issn = {1098-5522},
	doi = {10.1128/IAI.02801-14},
	author = {La Rosa, Sabina Leanti and Snipen, Lars-Gustav and Murray, Barbara E and Willems, Rob J L and Gilmore, Michael S and Diep, Dzung B and Nes, Ingolf F and Brede, Dag Anders}
}
@article {1664991,
	title = {The Controversy of Chronotherapy: Emerging Evidence regarding Bedtime Dosing of Antihypertensive Medications in Non-Arteritic Anterior Ischemic Optic Neuropathy},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {99-104},
	abstract = {"Blindness upon awakening" occurs in a significant proportion of patients with non-arteritic anterior ischemic optic neuropathy (NAION). This observation has led to a notion that nocturnal hypotension is a significant contributor and, perhaps, the final insult in a multifactorial process leading to the development of NAION, as has been proposed in other ischemic events like strokes, myocardial infarction, and ischemic rest pain. An extension of this concept has led to the recommendation that patients who have experienced NAION avoid taking blood pressure medications at bedtime. However, mounting evidence in the cardiology literature suggests that nocturnal hypertension is associated with increased risk of cardiovascular morbidity. In two prospective blood pressure monitoring studies in 1994 and 1999, Hayreh observed an extreme dipping pattern in nocturnal systolic blood pressure in NAION patients compared to reported normal values. Yet, two subsequent ambulatory blood pressure studies found either normal or non-dipping patterns in NAION patients. The majority of clinical trials published since 1976 that have studied nocturnal administration of antihypertensives have reported enhanced blood pressure control and reduced cardiovascular risk. Most notably, the large, prospective 2020 Hygia Chronotherapy Trial reported a statistically-significant beneficial effect of nocturnal antihypertensive dosing on cardiovascular outcomes and mortality. The controversy regarding nocturnal hypotension and NAION is of increasing relevance as there is new evidence to suggest a beneficial effect of nocturnal antihypertensive dosing in cardiovascular risk. This new information should prompt a re-evaluation of the relevant risk-to-benefit of reducing the risk of NAION on one hand, and the potential increase of cardiovascular risk on the other. Definitive resolution of this question would require a prospective, randomized control study with input from both cardiology and ophthalmology.},
	keywords = {Antihypertensive Agents, Blood Pressure Monitoring, Ambulatory, Chronotherapy, Humans, Hypotension, Optic Neuropathy, Ischemic, Prospective Studies},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152709},
	author = {Labowsky, Mary T and Rizzo, Joseph F}
}
@article {509171,
	title = {Focused Tortuosity Definitions Based on Expert Clinical Assessment of Corneal Subbasal Nerves.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {9},
	year = {2015},
	month = {2015 Aug 1},
	pages = {5102-9},
	abstract = {PURPOSE: We examined agreement among experts in the assessment of corneal subbasal nerve tortuosity. METHODS: Images of corneal subbasal nerves were obtained from investigators at seven sites (Auckland, Boston, Link{\"o}ping, Manchester, Oslo, Rostock, and Sydney) using laser-scanning in vivo confocal microscopy. A set of 30 images was assembled and ordered by increasing tortuosity by 10 expert graders from the seven sites. In a first experiment, graders assessed tortuosity without a specific definition and performed grading three times, with at least 1 week between sessions. In a second experiment, graders assessed the same image set using four focused tortuosity definitions. Intersession and intergrader repeatability for the experiments were determined using the Spearman rank correlation. RESULTS: Expert graders without a specific tortuosity definition had high intersession (Spearman correlation coefficient 0.80), but poor intergrader (0.62) repeatability. Specific definitions improved intergrader repeatability to 0.79. In particular, tortuosity defined by frequent small-amplitude directional changes (short range tortuosity) or by infrequent large-amplitude directional changes (long range tortuosity), indicated largely independent measures and resulted in improved repeatability across the graders. A further refinement, grading only the most tortuous nerve in a given image, improved the average correlation of a given grader{\textquoteright}s ordering of images with the group average to 0.86 to 0.90. CONCLUSIONS: Definitions of tortuosity specifying short or long-range tortuosity and considering only the most tortuous nerve in an image improved the agreement in tortuosity grading among a group of expert observers. These definitions could improve accuracy and consistency in quantifying subbasal nerve tortuosity in clinical studies.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17284},
	author = {Lagali, Neil and Poletti, Enea and Patel, Dipika V and McGhee, Charles N J and Hamrah, Pedram and Kheirkhah, Ahmad and Tavakoli, Mitra and Petropoulos, Ioannis N and Malik, Rayaz A and Utheim, Tor Paaske and Zhivov, Andrey and Stachs, Oliver and Falke, Karen and Peschel, Sabine and Guthoff, Rudolf and Chao, Cecilia and Golebiowski, Blanka and Stapleton, Fiona and Ruggeri, Alfredo}
}
@article {1402581,
	title = {Non-Synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma},
	journal = {Hum Mol Genet},
	volume = {28},
	number = {8},
	year = {2019},
	month = {2019 Apr 15},
	pages = {1298-1311},
	abstract = {Pigmentary glaucoma (PG) is a common glaucoma subtype that results from release of pigment from the iris, called pigment dispersion syndrome (PDS), and its deposition throughout the anterior chamber of the eye. Although PG has a substantial heritable component, no causative genes have yet been identified. We used whole exome sequencing of two independent pedigrees to identify two premelanosome protein (PMEL) variants associated with heritable PDS/PG. PMEL encodes a key component of the melanosome, the organelle essential for melanin synthesis, storage and transport. Targeted screening of PMEL in three independent cohorts (n\&nbsp;=\&nbsp;394) identified seven additional PDS/PG-associated non-synonymous variants. Five of the nine variants exhibited defective processing of the PMEL protein. In addition, analysis of PDS/PG-associated PMEL variants expressed in HeLa cells revealed structural changes to pseudomelanosomes indicating altered amyloid fibril formation in five of the nine variants. Introduction of 11-base pair deletions to the homologous pmela in zebrafish by the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 method caused profound pigmentation defects and enlarged anterior segments in the eye, further supporting PMEL{\textquoteright}s role in ocular pigmentation and function. Taken together, these data support a model in which missense PMEL variants represent dominant negative mutations that impair the ability of PMEL to form functional amyloid fibrils. While PMEL mutations have previously been shown to cause pigmentation and ocular defects in animals, this research is the first report of mutations in PMEL causing human disease.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddy429},
	author = {Lahola-Chomiak, Adrian A and Footz, Tim and Nguyen-Phuoc, Kim and Neil, Gavin J and Fan, Bao Jian and Allen, Keri F and Greenfield, David S and Parrish, Richard K and Linkroum, Kevin and Pasquale, Louis R and Leonhardt, Ralf M and Ritch, Robert and Javadiyan, Shari and Craig, Jamie E and Allison, W T and Lehmann, Ordan J and Walter, Michael A and Wiggs, Janey L}
}
@article {1078771,
	title = {Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy},
	journal = {PLoS One},
	volume = {12},
	number = {5},
	year = {2017},
	month = {2017},
	pages = {e0177749},
	abstract = {PURPOSE: To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. METHODS: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. RESULTS: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. CONCLUSION: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients{\textasciiacute} metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0177749},
	author = {La{\'\i}ns, In{\^e}s and Duarte, Daniela and Barros, Ant{\'o}nio S and Martins, Ana Sofia and Gil, Jo{\~a}o and Miller, John B and Marques, Marco and Mesquita, T{\^a}nia and Kim, Ivana K and Cachulo, Maria da Luz and Vavvas, Demetrios and Carreira, Isabel M and Murta, Joaquim N and Silva, Rufino and Miller, Joan W and Husain, Deeba and Gil, Ana M}
}
@article {1062831,
	title = {HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION},
	journal = {Retina},
	volume = {38},
	number = {6},
	year = {2018},
	month = {2018 Jun},
	pages = {1145-1155},
	abstract = {PURPOSE: To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD).

METHODS: Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage.

RESULTS: Seventy-eight subjects (75.6\% AMD; 24.4\% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time >= 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017).

CONCLUSION: Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001659},
	author = {La{\'\i}ns, In{\^e}s and Miller, John B and Mukai, Ryo and Mach, Steven and Vavvas, Demetrios and Kim, Ivana K and Miller, Joan W and Husain, Deeba}
}
@article {1761961,
	title = {Polychromatic Aqueous and Vitreous Crystals Due to Phacolytic Glaucoma in a Patient With Marfan Syndrome and Lens Dislocation},
	journal = {J Vitreoretin Dis},
	volume = {7},
	number = {5},
	year = {2023},
	month = {2023 Sep-Oct},
	pages = {435-439},
	abstract = {Purpose: To describe a patient with Marfan syndrome and crystalline lens luxation who developed phacolytic glaucoma with polychromatic crystals in the anterior chamber and vitreous. Methods: We present a retrospective case report. Results: A 58-year-old man with Marfan syndrome and crystalline lens luxation since childhood presented with 2 days of pain in the left eye. The visual acuity was 20/30 OS with an aphakic contact lens, and the intraocular pressure (IOP) was 31 mm Hg. Polychromatic crystals were evident in the anterior chamber and vitreous. The retina was attached. Despite medical treatment, the IOP remained elevated; therefore, a pars plana vitrectomy and lensectomy were performed. At the last follow-up, the IOP was normal and the retina remained attached. Conclusions: Phacolytic glaucoma can be seen in eyes with a subluxated or luxated mature or hypermature lens. In these rare cases, iridescent crystals can be observed in the aqueous and vitreous. Vitrectomy with lensectomy is the definitive treatment.},
	issn = {2474-1272},
	doi = {10.1177/24741264221103837},
	author = {Lains, Ines and Ung, Cindy and Gong, Dan and Parikh, Deep and Eliott, Dean}
}
@article {1424806,
	title = {Urine Nuclear Magnetic Resonance (NMR) Metabolomics in Age-Related Macular Degeneration},
	journal = {J Proteome Res},
	volume = {18},
	number = {3},
	year = {2019},
	month = {2019 Mar 01},
	pages = {1278-1288},
	abstract = {Biofluid biomarkers of age-related macular degeneration (AMD) are still lacking, and their identification is challenging. Metabolomics is well-suited to address this need, and urine is a valuable accessible biofluid. This study aimed to characterize the urinary metabolomic signatures of patients with different stages of AMD and a control group (\&gt;50 years). It was a prospective, cross-sectional study, where subjects from two cohorts were included: 305 from Coimbra, Portugal (AMD patients n = 252; controls n = 53) and 194 from Boston, United States (AMD patients n = 147; controls n = 47). For all participants, we obtained color fundus photographs (for AMD staging) and fasting urine samples, which were analyzed using H nuclear magnetic resonance (NMR) spectroscopy. Our results revealed that in both cohorts, urinary metabolomic profiles differed mostly between controls and late AMD patients, but important differences were also found between controls and subjects with early AMD. Analysis of the metabolites responsible for these separations revealed that, even though distinct features were observed for each cohort, AMD was in general associated with depletion of excreted citrate and selected amino acids at some stage of the disease, suggesting enhanced energy requirements. In conclusion, NMR metabolomics enabled the identification of urinary signals of AMD and its severity stages, which might represent potential metabolomic biomarkers of the disease.},
	issn = {1535-3907},
	doi = {10.1021/acs.jproteome.8b00877},
	author = {La{\'\i}ns, In{\^e}s and Duarte, Daniela and Barros, Ant{\'o}nio S and Martins, Ana Sofia and Carneiro, Tatiana J and Gil, Jo{\~a}o Q and Miller, John B and Marques, Marco and Mesquita, T{\^a}nia S and Barreto, Patr{\'\i}cia and Kim, Ivana K and da Luz Cachulo, Maria and Vavvas, Demetrios G and Carreira, Isabel M and Murta, Joaquim Neto and Silva, Rufino and Miller, Joan W and Husain, Deeba and Gil, Ana M}
}
@article {1580498,
	title = {BASELINE PREDICTORS ASSOCIATED WITH 3-YEAR CHANGES IN DARK ADAPTATION IN AGE-RELATED MACULAR DEGENERATION},
	journal = {Retina},
	volume = {41},
	number = {10},
	year = {2021},
	month = {2021 Oct 01},
	pages = {2098-2105},
	abstract = {PURPOSE: To assess the relationship between baseline age-related macular degeneration (AMD) and disease stage, as well as optical coherence tomography features seen in AMD, with 3-year changes in dark adaptation (DA). METHODS: Prospective longitudinal study including patients with AMD and a comparison group (n = 42 eyes, 27 patients). At baseline and 3 years, we obtained color fundus photographs, spectral-domain optical coherence tomography, and rod-mediated DA (20 minutes protocol). Multilevel mixed-effect models were used for analyses, with changes in rod intercept time at 3 years as the primary outcome. As some eyes (n = 11) reached the DA testing ceiling value at baseline, we used 3-year changes in area under the DA curve as an additional outcome. RESULTS: Baseline AMD, AMD stage, and hyperreflective foci on optical coherence tomography were associated with larger changes in rod intercept time at 3 years. When change in area under the DA curve was used as an outcome, in addition to these features, the presence of retinal atrophy and drusenoid pigment epithelial detachment had significant associations. New subretinal drusenoid deposits at 3 years were also associated with more pronounced changes in rod intercept time and area under the DA curve. CONCLUSION: Specific optical coherence tomography features are associated with DA impairments over time, which supports that structural changes predict functional loss over 3 years.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003152},
	author = {Lains, Ines and Pundlik, Shrinivas J and Nigalye, Archana and Katz, Raviv and Luo, Gang and Kim, Ivana K and Vavvas, Demetrios G and Miller, Joan W and Miller, John B and Husain, Deeba}
}
@article {1452970,
	title = {Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts},
	journal = {Metabolites},
	volume = {9},
	number = {7},
	year = {2019},
	month = {2019 Jul 02},
	abstract = {The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States ( = 196) and Coimbra, Portugal ( = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) -value: 4.1 {\texttimes} 10-1.8 {\texttimes} 10), and 67 across disease stages (FDR -value: 4.5 {\texttimes} 10-1.7 {\texttimes} 10). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (-value <= 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition.},
	issn = {2218-1989},
	doi = {10.3390/metabo9070127},
	author = {La{\'\i}ns, In{\^e}s and Chung, Wonil and Kelly, Rachel S and Gil, Jo{\~a}o and Marques, Marco and Barreto, Patr{\'\i}cia and Murta, Joaquim N and Kim, Ivana K and Vavvas, Demetrios G and Miller, John B and Silva, Rufino and Lasky-Su, Jessica and Liang, Liming and Miller, Joan W and Husain, Deeba}
}
@article {1302197,
	title = {Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers},
	journal = {Ophthalmology},
	volume = {125},
	number = {2},
	year = {2018},
	month = {2018 Feb},
	pages = {245-254},
	abstract = {PURPOSE: To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). DESIGN: Cross-sectional observational study. PARTICIPANTS: We prospectively recruited participants with a diagnosis of AMD and a control group (\&gt;50\&nbsp;years of age) without any vitreoretinal disease. METHODS: All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon{\textquoteright}s hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. MAIN OUTCOME MEASURES: The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. RESULTS: We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8\%; n\&nbsp;= 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2\%) also were significantly different across the\&nbsp;different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P\&nbsp;=\&nbsp;4.7\&nbsp;{\texttimes} 10) among these metabolites. CONCLUSIONS: Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest that the most significant metabolites map to the glycerophospholipid pathway. These findings have the potential to improve our understanding of AMD pathogenesis, to support the development of plasma-based metabolomics biomarkers of AMD, and to identify novel targets for treatment of this blinding disease.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.08.008},
	author = {La{\'\i}ns, In{\^e}s and Kelly, Rachel S and Miller, John B and Silva, Rufino and Vavvas, Demetrios G and Kim, Ivana K and Murta, Joaquim N and Lasky-Su, Jessica and Miller, Joan W and Husain, Deeba}
}
@article {1109836,
	title = {Choroidal Changes Associated With Subretinal Drusenoid Deposits in Age-related Macular Degeneration Using Swept-source Optical Coherence Tomography},
	journal = {Am J Ophthalmol},
	volume = {180},
	year = {2017},
	month = {2017 Aug},
	pages = {55-63},
	abstract = {PURPOSE: To compare choroidal vascular features of eyes with and without subretinal drusenoid deposits (SDD), using swept-source optical coherence tomography (SS OCT). DESIGN: Multicenter, cross-sectional study. METHODS: We prospectively recruited patients with intermediate age-related macular degeneration (AMD), without other vitreoretinal pathology. All participants underwent complete ophthalmic examination, color fundus photography (used for AMD staging), and spectral-domain OCT (to evaluate the presence of SDD). SS OCT was used to obtain automatic macular choroidal thickness (CT) maps, according to the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. For data analysis, we considered mean choroidal thickness as the arithmetic mean value of the 9 ETDRS sectors. SS OCT en face images of choroidal vasculature were also captured and converted to binary images. Choroidal vascular density (CVD) was calculated as a percent area occupied by choroidal vessels in a 6-mm-diameter submacular circular. Choroidal vessel volume was calculated by multiplying the average CVD by macular area and CT. Multilevel mixed linear models (to account for the inclusion of 2 eyes of same subject) were performed for analysis. RESULTS: We included 186 eyes (n\&nbsp;= 118 subjects), 94 (50.5\%) presenting SDD. Multiple regression analysis revealed that, controlling for age, eyes with SDD presented a statistically thinner mean CT ({\ss}\&nbsp;=\&nbsp;-21.9, P\&nbsp;= .006) and CT in all the individual ETDRS fields ({\ss} <=\&nbsp;-18.79, P <= .026). Mean choroidal vessel volume was also significantly reduced in eyes with SDD ({\ss}\&nbsp;=\&nbsp;-0.003, P\&nbsp;= .007). No significant associations were observed with mean CVD. CONCLUSION: In subjects with intermediate AMD, choroidal thickness and vessel volume are reduced in the presence of subretinal drusenoid deposits.},
	keywords = {Aged, Aged, 80 and over, Choroid, Choroidal Neovascularization, Cross-Sectional Studies, Female, Fluorescein Angiography, Humans, Male, Prospective Studies, Retinal Drusen, Surveys and Questionnaires, Tomography, Optical Coherence, Wet Macular Degeneration},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.05.021},
	author = {La{\'\i}ns, In{\^e}s and Wang, Jay and Provid{\^e}ncia, Joana and Mach, Steven and Gil, Pedro and Gil, Jo{\~a}o and Marques, Marco and Armstrong, Grayson and Garas, Shady and Barreto, Patr{\'\i}cia and Kim, Ivana K and Vavvas, Demetrios G and Miller, Joan W and Husain, Deeba and Silva, Rufino and Miller, John B}
}
@article {1632297,
	title = {Urinary Mass Spectrometry Profiles in Age-Related Macular Degeneration},
	journal = {J Clin Med},
	volume = {11},
	number = {4},
	year = {2022},
	month = {2022 Feb 11},
	abstract = {We and others have shown that patients with different severity stages of age-related macular degeneration (AMD) have distinct plasma metabolomic profiles compared to controls. Urine is a biofluid that can be obtained non-invasively and, in other fields, urine metabolomics has been proposed as a feasible alternative to plasma biomarkers. However, no studies have applied urinary mass spectrometry (MS) metabolomics to AMD. This study aimed to assess urinary metabolomic profiles of patients with different stages of AMD and a control group. We included two prospectively designed, multicenter, cross-sectional study cohorts: Boston, US (n = 185) and Coimbra, Portugal (n = 299). We collected fasting urine samples, which were used for metabolomic profiling (Ultrahigh Performance Liquid chromatography-Mass Spectrometry). Multivariable logistic and ordinal logistic regression models were used for analysis, accounting for gender, age, body mass index and use of AREDS supplementation. Results from both cohorts were then meta-analyzed. No significant differences in urine metabolites were seen when comparing patients with AMD and controls. When disease severity was considered as an outcome, six urinary metabolites differed significantly (p \&lt; 0.01). In particular, two of the metabolites identified have been previously shown by our group to also differ in the plasma of patients of AMD compared to controls and across severity stages. While there are fewer urinary metabolites associated with AMD than plasma metabolites, this study identified some differences across stages of disease that support previous work performed with plasma, thus highlighting the potential of these metabolites as future biomarkers for AMD.},
	issn = {2077-0383},
	doi = {10.3390/jcm11040940},
	author = {Lains, Ines and Mendez, Kevin M and Gil, Jo{\~a}o Q and Miller, John B and Kelly, Rachel S and Barreto, Patr{\'\i}cia and Kim, Ivana K and Vavvas, Demetrios G and Murta, Joaquim Neto and Liang, Liming and Silva, Rufino and Miller, Joan W and Lasky-Su, Jessica and Husain, Deeba}
}
@article {1798426,
	title = {Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration},
	journal = {Ophthalmol Sci},
	volume = {4},
	number = {1},
	year = {2024},
	month = {2024 Jan-Feb},
	pages = {100357},
	abstract = {PURPOSE: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD.

DESIGN: Prospectively designed, cross-sectional study.

PARTICIPANTS: Subjects with a diagnosis of AMD and a control group (\&gt; 50 years old) from Boston, United States, and Coimbra, Portugal.

METHODS: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons.

MAIN OUTCOME MEASURES: Plasma metabolite levels associated with OCT features.

RESULTS: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR \&lt; 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed.

CONCLUSIONS: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100357},
	author = {Lains, Ines and Han, Xikun and Gil, Jo{\~a}o and Providencia, Joana and Nigalye, Archana and Alvarez, Rodrigo and Douglas, Vivian Paraskevi and Mendez, Kevin and Katz, Raviv and Tsougranis, Gregory and Li, Jinglun and Kelly, Rachel S and Kim, Ivana K and Lasky-Su, Jessica and Silva, Rufino and Miller, Joan W and Liang, Liming and Vavvas, Demetrios and Miller, John B and Husain, Deeba}
}
@article {1309967,
	title = {Peripheral Changes Associated With Delayed Dark Adaptation in Age-related Macular Degeneration},
	journal = {Am J Ophthalmol},
	volume = {190},
	year = {2018},
	month = {2018 Jun},
	pages = {113-124},
	abstract = {PURPOSE: To study the association between peripheral changes in age-related macular degeneration (AMD) and dark adaptation (DA).

DESIGN: Prospective, cross-sectional study.

METHODS: We recruited patients with AMD and a control group (>50 years) without any vitreoretinal disease. Ultra-widefield (UWF) pseudocolor and fundus autofluorescence (FAF) were obtained, and were assessed by 2 graders for the presence of several peripheral changes in perimacular, midperipheral, and far-peripheral zones. All participants were also imaged with 7-field color fundus photographs used for AMD staging (Age-Related Eye Disease Study classification system). Both eyes of study participants were tested with a dark adaptation (DA) extended protocol (20~minutes). Multilevel mixed-effect models (accounting for correlated outcomes between 2 eyes) were used for analyses.

RESULTS: We included 128 eyes (n~= 72 patients), 75\% with AMD and the remainder controls. The presence of reticular pigmentary changes in the midperipheral ({\ss}~= 4.3, P~= .012) and far-peripheral zones ({\ss}~= 8.4, P~< .001) was associated with delayed rod-intercept times (RITs), even after adjusting for confounding factors. The presence, number, and extent of peripheral classic drusen did not show a similar association (P >= .148). The presence of a mottled decreased FAF pattern in the midperipheral zone was also associated with prolonged RITs (β~= 4.4, P~= .031).

CONCLUSION: Our results suggest an association between DA and the presence of peripheral reticular pigmentary changes, as well as the presence of a peripheral mottled decreased FAF pattern. This provides new insights on the clinical significance of peripheral changes in AMD, and their contribution to impairments on DA.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.03.035},
	author = {La{\'\i}ns, In{\^e}s and Park, Dong Ho and Mukai, Ryo and Silverman, Rebecca and Oellers, Patrick and Mach, Steven and Kim, Ivana K and Vavvas, Demetrios G and Miller, Joan W and Miller, John B and Husain, Deeba}
}
@article {1782286,
	title = {Compassionomics: The Science and Practice of Caring},
	journal = {Am J Ophthalmol},
	volume = {259},
	year = {2024},
	month = {2024 Mar},
	pages = {15-24},
	abstract = {PURPOSE: To summarize the scientific evidence that compassion can measurably improve patient outcomes, health care quality and safety, and the well-being of health care providers, and to consider specific strategies for cultivating compassion and better communicating it to patients. DESIGN: Perspective. METHODS: We selectively reviewed the literature on compassion in health care, including obstacles to its expression and the demonstrated effects of provider compassion on patient outcomes, health care quality and cost, and provider well-being. We also review evidence regarding the trainability of compassion, discuss proven methods for cultivating individual compassion, and recommend strategies for incorporating it into routine medical practice. RESULTS: Compassion is the emotional response to another{\textquoteright}s pain or suffering, accompanied by a desire to alleviate it. Review of the literature shows that compassionate health care measurably improves physical and psychological patient outcomes, increases patient adherence, improves health care quality and safety, increases financial margins, and prevents physician burnout. Psychophysiological research shows that empathy and compassion can be actively cultivated through intentional practice. Validated models of compassion-based interactions can facilitate the consistent expression of compassion in daily medical practice. CONCLUSIONS: Given its many proven benefits to patients, health care organizations, and providers, compassion should be cultivated by health care providers and systems and considered an essential component of optimal medical care.},
	keywords = {Anxiety, Delivery of Health Care, Empathy, Health Personnel, Humans, Physicians},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.10.006},
	author = {Lains, Ines and Johnson, Taylor J and Johnson, Mark W}
}
@article {691756,
	title = {Second primary neoplasms in patients with uveal melanoma: a SEER database analysis.},
	journal = {Am J Ophthalmol},
	year = {2016},
	month = {2016 Feb 29},
	abstract = {PURPOSE: To determine the risk of second primary neoplasms (SPNs) in subjects previously diagnosed with uveal melanoma (UM), including an analysis on whether radiotherapy is a risk factor to develop these SPNs. DESIGN: Retrospective cohort study. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) 9 database, we identified patients diagnosed with UM as their first malignancy between 1973 and 2011 (n= 3,976). We obtained standardized incidence ratios (SIR) and excess absolute risks of SPNs on patients with UM compared to a reference population. Multivariate Cox regression models were used to evaluate the effect of radiotherapy in SPNs risk. RESULTS: Sixteen percent (n= 641) of the patients developed SPNs during a median follow-up of 83 months (range: 1 - 463 months). This represented an 11\% excess risk compared to the reference population, mainly due to a significantly increased risk of skin melanomas (SIR= 2.93, 95\% CI: 2.23 - 3.78) and kidney tumors (SIR= 1.91, 95\% CI: 1.27 - 2.76), primarily in those diagnosed between 30-59 years. The occurrence of second UM was also increased (SIR= 16.90, 95\% CI: 9.00 - 28.90), which likely includes recurrences misclassified as a second cancer. Radiotherapy was performed in 39\% (n= 1,538) of the patients. Multivariate analysis revealed that this treatment was not an independent risk factor for SPNs (Hazard Ratio= 1.06, 95\% CI: 0.88 - 1.26, p= 0.54). CONCLUSIONS: Patients with UM presented an 11\% higher risk of SPNs compared to the reference population. Radiotherapy does not seem to be a risk factor. SPNs should be considered in the surveillance of UM.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.02.022},
	author = {La{\'\i}ns, In{\^e}s and Bartosch, Carla and Mondim, Vera and Healy, Brian and Kim, Ivana and Husain, Deeba and Miller, Joan W}
}
@article {1323932,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {125},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {e46-e47},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.02.026},
	author = {La{\'\i}ns, In{\^e}s and Kelly, Rachel S and Miller, John B and Vavvas, Demetrios G and Kim, Ivana K and Lasky-Su, Jessica and Miller, Joan W and Husain, Deeba}
}
@article {1078766,
	title = {Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration},
	journal = {Ophthalmology},
	volume = {124},
	number = {9},
	year = {2017},
	month = {2017 Sep},
	pages = {1340-1352},
	abstract = {PURPOSE: To examine the relationship between dark adaptation (DA) and optical coherence tomography (OCT)-based macular morphology in age-related macular degeneration (AMD). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Patients with AMD and a comparison group (\&gt;50 years) without any vitreoretinal disease. METHODS: All participants were imaged with spectral-domain OCT and color fundus photographs, and then staged for AMD (Age-related Eye Disease Study system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA extended protocol (20 minutes). A software program was developed to map the DA testing spot (2{\textdegree} circle, 5{\textdegree} superior to the fovea) to the OCT B-scans. Two independent graders evaluated the B-scans within this testing spot, as well as the entire macula, recording the presence of several AMD-associated abnormalities. Multilevel mixed-effects models (accounting for correlated outcomes between 2 eyes) were used for analyses. MAIN OUTCOME MEASURES: The primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous variable. For subjects unable to reach RIT within the 20 minutes of testing, the value of 20 was assigned. RESULTS: We included 137 eyes (n\&nbsp;= 77 subjects), 72.3\% (n\&nbsp;= 99 eyes) with AMD and the remainder belonging to the comparison group. Multivariable analysis revealed that even after adjusting for age and AMD stage, the presence of any abnormalities within the DA testing spot ({\ss}\&nbsp;= 4.8, P \&lt; 0.001), as well as any abnormalities in the macula ({\ss}\&nbsp;= 2.4, P\&nbsp;= 0.047), were significantly associated with delayed RITs and therefore impaired DA. In eyes with no structural changes within the DA testing spot (n\&nbsp;= 76, 55.5\%), the presence of any abnormalities in the remaining macula was still associated with delayed RITs ({\ss}\&nbsp;= 2.00, P\&nbsp;= 0.046). Presence of subretinal drusenoid deposits and ellipsoid zone disruption were a consistent predictor of RIT, whether located within the DA testing spot (P\&nbsp;= 0.001 for both) or anywhere in the macula (P \&lt; 0.001 for both). Within the testing spot, the presence of classic drusen or serous pigment epithelium detachment was also significantly associated with impairments in DA (P <= 0.018). CONCLUSIONS: Our results suggest a significant association between macular morphology evaluated by OCT and time to dark-adapt. Subretinal drusenoid deposits and ellipsoid zone changes seem to be strongly associated with impaired dark adaptation.},
	keywords = {Aged, Aged, 80 and over, Cross-Sectional Studies, Dark Adaptation, Diagnostic Techniques, Ophthalmological, Female, Geographic Atrophy, Humans, Male, Middle Aged, Prospective Studies, Sensory Thresholds, Tomography, Optical Coherence, Wet Macular Degeneration},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.03.061},
	author = {La{\'\i}ns, In{\^e}s and Miller, John B and Park, Dong H and Tsikata, Edem and Davoudi, Samaneh and Rahmani, Safa and Pierce, Jonathan and Silva, Rufino and Chen, Teresa C and Kim, Ivana K and Vavvas, Demetrios and Miller, Joan W and Husain, Deeba}
}
@article {1016096,
	title = {CHOROIDAL THICKNESS IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY},
	journal = {Retina},
	volume = {38},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {173-182},
	abstract = {PURPOSE: To compare the choroidal thickness (CT) of diabetic eyes (different stages of disease) with controls, using swept-source optical coherence tomography. METHODS: A multicenter, prospective, cross-sectional study of diabetic and nondiabetic subjects using swept-source optical coherence tomography imaging. Choroidal thickness maps, according to the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, were obtained using automated software. Mean CT was calculated as the mean value within the ETDRS grid, and central CT as the mean in the central 1 mm. Diabetic eyes were divided into four groups: no diabetic retinopathy (No DR), nonproliferative DR (NPDR), NPDR with diabetic macular edema (NPDR + DME), and proliferative DR (PDR). Multilevel mixed linear models were performed for analyses. RESULTS: The authors included 50 control and 160 diabetic eyes (n = 27 No DR, n = 51 NPDR, n = 61 NPDR + DME, and n = 21 PDR). Mean CT ({\ss} = -42.9, P = 0.022) and central CT ({\ss} = -50.2, P = 0.013) were statistically significantly thinner in PDR eyes compared with controls, even after adjusting for confounding factors. Controlling for age, DR eyes presented a significantly decreased central CT than diabetic eyes without retinopathy (β = -36.2, P = 0.009). CONCLUSION: Swept-source optical coherence tomography demonstrates a significant reduction of CT in PDR compared with controls. In the foveal region, the choroid appears to be thinner in DR eyes than in diabetic eyes without retinopathy.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001516},
	author = {La{\'\i}ns, In{\^e}s and Talcott, Katherine E and Santos, Ana R and Marques, Jo{\~a}o H and Gil, Pedro and Gil, Jo{\~a}o and Figueira, Jo{\~a}o and Husain, Deeba and Kim, Ivana K and Miller, Joan W and Silva, Rufino and Miller, John B}
}
@article {1573124,
	title = {Anterior Ischemic Optic Neuropathy Secondary to Carotid Artery Dissection},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {4},
	year = {2021},
	month = {2021 Dec 01},
	pages = {e731-e733},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001161},
	author = {Lains, Ines and Diaz, Jose D and Gittinger, John W and Gaier, Eric D}
}
@article {1615217,
	title = {Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA)},
	journal = {Prog Retin Eye Res},
	volume = {84},
	year = {2021},
	month = {2021 Sep},
	pages = {100951},
	abstract = {The advent of optical coherence tomography (OCT) revolutionized both clinical assessment and research of vitreoretinal conditions. Since then, extraordinary advances have been made in this imaging technology, including the relatively recent development of swept-source OCT (SS-OCT). SS-OCT enables a fast scan rate and utilizes a tunable swept laser, thus enabling the incorporation of longer wavelengths than conventional spectral-domain devices. These features enable imaging of larger areas with reduced motion artifact, and a better visualization of the choroidal vasculature, respectively. Building on the principles of OCT, swept-source OCT has also been applied to OCT angiography (SS-OCTA), thus enabling a non-invasive in depth-resolved imaging of the retinal and choroidal microvasculature. Despite their advantages, the widespread use of SS-OCT and SS-OCTA remains relatively limited. In this review, we summarize the technical details, advantages and limitations of SS-OCT and SS-OCTA, with a particular emphasis on their relevance for the study of retinal conditions. Additionally, we comprehensively review relevant studies performed to date to the study of retinal health and disease, and highlight current gaps in knowledge and opportunities to take advantage of swept source technology to improve our current understanding of many medical and surgical chorioretinal conditions. We anticipate that SS-OCT and SS-OCTA will continue to evolve rapidly, contributing to a paradigm shift to more widespread adoption of new imaging technology to clinical practice.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2021.100951},
	author = {La{\'\i}ns, In{\^e}s and Wang, Jay C and Cui, Ying and Katz, Raviv and Vingopoulos, Filippos and Staurenghi, Giovanni and Vavvas, Demetrios G and Miller, Joan W and Miller, John B}
}
@article {1629457,
	title = {Plasma Metabolomic Profiles Associated with Three-Year Progression of Age-Related Macular Degeneration},
	journal = {Metabolites},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 Jan 01},
	abstract = {Plasma metabolomic profiles have been shown to be associated with age-related macular degeneration (AMD) and its severity stages. However, all studies performed to date have been cross-sectional and have not assessed progression of AMD. This prospective, longitudinal, pilot study analyzes, for the first time, the association between plasma metabolomic profiles and progression of AMD over a 3-year period. At baseline and 3 years later, subjects with AMD (n = 108 eyes) and controls (n = 45 eyes) were imaged with color fundus photos for AMD staging and tested for retinal function with dark adaptation (DA). Fasting plasma samples were also collected for metabolomic profiling. AMD progression was considered present if AMD stage at 3 years was more advanced than at baseline (n = 26 eyes, 17\%). Results showed that, of the metabolites measured at baseline, eight were associated with 3-year AMD progression (p \&lt; 0.01) and 19 (p \&lt; 0.01) with changes in DA. Additionally, changes in the levels (i.e., between 3 years and baseline) of 6 and 17 metabolites demonstrated significant associations (p \&lt; 0.01) with AMD progression and DA, respectively. In conclusion, plasma metabolomic profiles are associated with clinical and functional progression of AMD at 3 years. These findings contribute to our understanding of mechanisms of AMD progression and the identification of potential therapeutics for this blinding disease.},
	issn = {2218-1989},
	doi = {10.3390/metabo12010032},
	author = {Lains, Ines and Mendez, Kevin and Nigalye, Archana and Katz, Raviv and Douglas, Vivian Paraskevi and Kelly, Rachel S and Kim, Ivana K and Miller, John B and Vavvas, Demetrios G and Liang, Liming and Lasky-Su, Jessica and Miller, Joan W and Husain, Deeba}
}
@article {1460363,
	title = {CLOSURE OF SMALL MACULAR HOLES USING VITRECTOMY SURGERY WITH INTERNAL LIMITING MEMBRANE PEELING WITHOUT THE USE OF INTRAOCULAR GAS TAMPONADE: BROADENING THE UNDERSTANDING OF THE MACULAR HOLE PATHOPHYSIOLOGY},
	journal = {Retin Cases Brief Rep},
	volume = {14},
	number = {2},
	year = {2020},
	month = {2020 Spring},
	pages = {104-109},
	abstract = {PURPOSE: To determine whether small macular hole closure can be achieved with 25-G vitrectomy surgery with internal limiting membrane peeling without the use of intraocular gas tamponade or facedown positioning. METHODS: 25-G vitrectomy surgery with internal limiting membrane peeling without the use of intraocular gas tamponade or positioning was performed on 20 eyes with a small (\&lt;400-{\textmu}m diameter), full-thickness macular hole. RESULTS: In 17 of 20 eyes (85\%), the hole had closed. Three holes had closed by Postoperative Day 1, 13 holes by Postoperative Week 1, 16 holes by Postoperative Week 2, and 17 holes by Postoperative Week 6. At Postoperative Month 1, vision improved in 16 of 17 eyes in which the macular hole had closed. One hole that had not closed at the first postoperative week and two holes that had not closed at the third postoperative week required follow-up surgery with intraocular gas tamponade and facedown positioning, after which the hole closed. The mean preoperative visual acuity was 0.626 logMAR (20/85), and the mean postoperative visual acuity after 1 month was 0.392 logMAR (20/50) (P \&lt; 0.001). CONCLUSION: Vitrectomy surgery with internal limiting membrane peeling without the use of gas tamponade or positioning can achieve closure of small macular holes.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000919},
	author = {Lally, David R and Kasetty, Megan A}
}
@article {1059776,
	title = {Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis},
	journal = {Diabetes},
	volume = {66},
	number = {7},
	year = {2017},
	month = {2017 Jul},
	pages = {1950-1956},
	abstract = {Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world{\textquoteright}s working adult population and affects those with type 1 and type 2 diabetes. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31(+) vascular endothelial cells obtained from human PDR fibrovascular membranes (FVMs) via transcriptomic analysis. In vitro studies using human retinal microvascular endothelial cells (HRMECs) showed increased RUNX1 RNA and protein expression in response to high glucose, whereas RUNX1 inhibition reduced HRMEC migration, proliferation, and tube formation. Immunohistochemical staining for RUNX1 showed reactivity in vessels of patient-derived FVMs and angiogenic tufts in the retina of mice with oxygen-induced retinopathy, suggesting that RUNX1 upregulation is a hallmark of aberrant retinal angiogenesis. Inhibition of RUNX1 activity with the Ro5-3335 small molecule resulted in a significant reduction of neovascular tufts in oxygen-induced retinopathy, supporting the feasibility of targeting RUNX1 in aberrant retinal angiogenesis.},
	issn = {1939-327X},
	doi = {10.2337/db16-1035},
	author = {Lam, Jonathan D and Oh, Daniel J and Wong, Lindsay L and Amarnani, Dhanesh and Park-Windhol, Cindy and Sanchez, Angie V and Cardona-Velez, Jonathan and McGuone, Declan and Stemmer-Rachamimov, Anat O and Eliott, Dean and Bielenberg, Diane R and van Zyl, Tave and Shen, Lishuang and Gai, Xiaowu and D{\textquoteright}Amore, Patricia A and Kim, Leo A and Arboleda-Velasquez, Joseph F}
}
@article {1483623,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {127},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {e6-e7},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.09.017},
	author = {Lambert, Scott R and VanderVeen, Deborah K and Kim, Stephen J}
}
@article {1309962,
	title = {Contact Lens Correction of Aphakia in Children: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {125},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {1452-1458},
	abstract = {PURPOSE: To review the published literature to assess the visual outcomes and adverse events associated with the 2 most commonly used contact lenses for treating aphakia in children: silicone elastomer (SE) and rigid gas permeable (RGP). METHODS: Literature searches were last conducted in January 2018 in the PubMed, Cochrane Library, and ClinicalTrials.gov databases with no date or language restrictions. These combined searches yielded 167 citations, 27 of which were reviewed in full text. Of these, 10 articles were deemed appropriate for inclusion in this assessment and subsequently assigned a level of evidence rating by the panel methodologist. RESULTS: The literature search identified 4 level II studies and 6 level III studies. There were insufficient data to compare visual outcomes for eyes treated using SE lenses versus RGP lenses. Silicone elastomer lenses have the advantage that they can be worn on an extended-wear basis, but they were associated with more adverse events than RGP lenses. These adverse events included microbial keratitis, corneal infiltrates, corneal edema, corneal scars, lenses adhering to the cornea, superficial punctate keratopathy, lid swelling, and conjunctival hyperemia. The lens replacement rate was approximately 50\% higher for RGP lenses in the only study that directly compared SE and RGP lenses. CONCLUSIONS: Limited evidence was found in the literature on this topic. Silicone elastomer and RGP contact lenses were found to be effective for treating aphakia in children. Silicone elastomer lenses are easier to fit and may be worn on an extended-wear basis. Rigid gas permeable lenses must be removed every night and require a more customized fit, but they are associated with fewer adverse events. The choice of which lens a practitioner prescribes should be based on the particular needs of each patient.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.03.014},
	author = {Lambert, Scott R and Kraker, Raymond T and Pineles, Stacy L and Hutchinson, Amy K and Wilson, Lorri B and Galvin, Jennifer A and VanderVeen, Deborah K}
}
@article {1445324,
	title = {Intraocular Lens Implantation during Early Childhood: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {126},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {1454-1461},
	abstract = {PURPOSE: To compare the visual outcomes and adverse events associated with optical correction using an intraocular lens (IOL), contact lenses, or spectacles after cataract surgery in children 2 years of age or younger. METHODS: Literature searches were conducted in PubMed, the Cochrane Library, and the databases of clinical trials in February 2019, without date or language restrictions. The search resulted in 194 potentially relevant citations, and 34 were selected for full-text review. Fourteen studies were determined to be relevant to the assessment criteria and were selected for inclusion in this assessment. The panel methodologist then assigned a level of evidence rating to these studies. RESULTS: Intraocular lenses were associated with visual outcomes similar to outcomes for contact lenses or spectacles for children who had both bilateral and unilateral cataracts. Intraocular lenses were also associated with an increased risk of visual axis opacities. All treatments were associated with a similar incidence of glaucoma. Although ocular growth was similar for all treatments, infants younger than 6 months who underwent IOL implantation had large myopic shifts that often resulted in high myopia or severe anisometropia later in childhood. Corneal endothelial cell counts were lower in eyes that underwent IOL implantation. The incidence of strabismus was similar with all treatments. CONCLUSIONS: Intraocular lens implantation is not recommended for children 6 months of age or younger because there is a higher incidence of visual axis opacities with this treatment compared with aphakia. The best available evidence suggests that IOL implantation can be done safely with acceptable side effects in children older than 6 months of age. However, the unpredictability of ocular growth means that these children will often have large refractive errors later in childhood that may necessitate an IOL exchange or wearing spectacles or contact lenses with a large refractive correction. In addition, the training and experience of the surgeon as well as ocular and systemic comorbidities should be taken into consideration when deciding whether IOL implantation would be appropriate.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.05.009},
	author = {Lambert, Scott R and Aakalu, Vinay K and Hutchinson, Amy K and Pineles, Stacy L and Galvin, Jennifer A and Heidary, Gena and Binenbaum, Gil and VanderVeen, Deborah K}
}
@article {1483622,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {127},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {e8-e9},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.09.040},
	author = {Lambert, Scott R and VanderVeen, Deborah K and Aakalu, Vinay K and Kim, Stephen J}
}
@article {987991,
	title = {A Two-Week, Randomized, Double-masked Study to Evaluate Safety and Efficacy of Lubricin (150 μg/mL) Eye Drops Versus Sodium Hyaluronate (HA) 0.18\% Eye Drops (Vismed{\textregistered}) in Patients with Moderate Dry Eye Disease.},
	journal = {Ocul Surf},
	volume = {15},
	number = {1},
	year = {2017},
	pages = {77-87},
	abstract = {PURPOSE: The objective of this clinical trial (NCT02507934) was to assess the efficacy and safety of recombinant human lubricin as compared to a 0.18\% sodium hyaluronate (HA) eye drop in subjects with moderate dry eye disease (DED). METHODS: DEWS Grade 2-3 subjects were randomized to use lubricin (N=19, 51.9\&nbsp;{\textpm}\&nbsp;11.8\&nbsp;years) or HA (N=20, 61.8\&nbsp;{\textpm}\&nbsp;13.3\&nbsp;years). After a saline washout period, subjects administered BID therapy for 7\&nbsp;days, followed by instillation as needed (2-6 drops per eye) for 7\&nbsp;days. Visual analog scale (VAS) including foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision and photophobia were primary outcomes, with secondary endpoints of corneal fluorescein staining, Schirmer test, tear film breakup time (TFBUT), eyelid and conjunctival erythema and number of instillations compared at day\&nbsp;14. RESULTS: The primary endpoint was met. Lubricin supplementation achieved greater than a 72\% reduction from baseline in foreign body sensation (P\&lt;.013), burning/stinging, pain, sticky feeling (P\&lt;.0432), blurred vision (P\&lt;.0013), and photophobia (P\&lt;.011) in at least one eye. Lubricin also showed significant improvement in fluorescein staining (OD/OS: 43.8\%/50.0\%, vs. 26.5\%/23.3\%, P\&lt;.0398, P\&lt;.0232), TFBUT (P\&lt;.010), SANDE frequency (P\&lt;.0435), eyelid erythema (P\&lt;.004), conjunctival erythema (P\&lt;.0013), and instillations (P\&lt;.04) as compared to HA. No treatment-related adverse events occurred during the investigation. CONCLUSIONS: Recombinant human lubricin was shown to produce significant improvement in both signs and symptoms of dry eye disease as compared to HA.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2016.08.004},
	author = {Lambiase, Alessandro and Sullivan, Benjamin D and Schmidt, Tannin A and Sullivan, David A and Jay, Gregory D and Truitt, Edward R and Bruscolini, Alice and Sacchetti, Marta and Mantelli, Flavio}
}
@article {1359935,
	title = {Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {13},
	year = {2018},
	month = {2018 Nov 01},
	pages = {5633-5640},
	abstract = {Purpose: We evaluate diabetic microaneurysm (MA) features on high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) and their correlations with visual acuity (VA) and local retinal pathology on spectral domain optical coherence tomography (SDOCT). Methods: Diabetic participants underwent VA testing and AOSLO and SDOCT imaging of MAs. AOSLO images were graded for MA dimension, wall hyperreflectivity (WH), intraluminal hyperreflectivity (IH), and perfusion pattern. SDOCTs centered on each MA were graded for disorganization of the retinal inner layers (DRIL) and other neuroretinal pathology. Results: We imaged 109 MAs (30 eyes). Multivariate modeling, including statistically significant covariates from bivariate analyses, associated WH with greater MA size (P = 0.001) and DRIL (P = 0.04). IH was associated with perfusion (P = 0.003) and MA visibility on photographs (P = 0.0001), and larger MA size with partial perfusion (P = 0.03), MA ring signs (P = 0.0002), and photographic visibility (P = 0.01). Multivariate modeling revealed an association of WH and VA with DRIL. Conclusions: AOSLO imaging demonstrates associations of hyperreflective MA walls with MA size and adjacent DRIL, as well as the presence of DRIL with lower VA. This study identifies a correlation between vascular and neural pathology associated with VA decline. Further studies of MA structure and neuroretinal disorganization may enable novel approaches to assess anatomic and functional outcomes in the diabetic eye.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-24386},
	author = {Lammer, Jan and Karst, Sonja G and Lin, Michael M and Cheney, Michael and Silva, Paolo S and Burns, Stephen A and Aiello, Lloyd Paul and Sun, Jennifer K}
}
@article {961731,
	title = {Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {15},
	year = {2016},
	month = {2016 Dec 01},
	pages = {6624-6632},
	abstract = {Purpose: To determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME). Methods: Participants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated. Results: Fifty-three eyes (53 subjects) were assessed. Mean {\textpm} SD age was 44 {\textpm} 12 years; 81\% had DM (duration: 22 {\textpm} 13 years; glycated hemoglobin [HbA1c]: 8.0 {\textpm} 1.7\%; DM type 1: 72\%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04). Conclusions: Although absolute cone density and spacing don{\textquoteright}t appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-19537},
	author = {Lammer, Jan and Prager, Sonja G and Cheney, Michael C and Ahmed, Amel and Radwan, Salma H and Burns, Stephen A and Silva, Paolo S and Sun, Jennifer K}
}
@article {931106,
	title = {Expansion of phenotype and genotypic data in CRB2-related syndrome.},
	journal = {Eur J Hum Genet},
	volume = {24},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {1436-44},
	abstract = {Sequence variants in CRB2 cause a syndrome with greatly elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein levels, cerebral ventriculomegaly and renal findings similar to Finnish congenital nephrosis. All reported patients have been homozygotes or compound heterozygotes for sequence variants in the Crumbs, Drosophila, Homolog of, 2 (CRB2) genes. Variants affecting CRB2 function have also been identified in four families with steroid resistant nephrotic syndrome, but without any other known systemic findings. We ascertained five, previously unreported individuals with biallelic variants in CRB2 that were predicted to affect function. We compiled the clinical features of reported cases and reviewed available literature for cases with features suggestive of CRB2-related syndrome in order to better understand the phenotypic and genotypic manifestations. Phenotypic analyses showed that ventriculomegaly was a common clinical manifestation (9/11 confirmed cases), in contrast to the original reports, in which patients were ascertained due to renal disease. Two children had minor eye findings and one was diagnosed with a B-cell lymphoma. Further genetic analysis identified one family with two affected siblings who were both heterozygous for a variant in NPHS2 predicted to affect function and separate families with sequence variants in NPHS4 and BBS7 in addition to the CRB2 variants. Our report expands the clinical phenotype of CRB2-related syndrome and establishes ventriculomegaly and hydrocephalus as frequent manifestations. We found additional sequence variants in genes involved in kidney development and ciliopathies in patients with CRB2-related syndrome, suggesting that these variants may modify the phenotype.},
	issn = {1476-5438},
	doi = {10.1038/ejhg.2016.24},
	author = {Lamont, Ryan E and Tan, Wen-Hann and Innes, A Micheil and Parboosingh, Jillian S and Schneidman-Duhovny, Dina and Rajkovic, Aleksandar and Pappas, John and Altschwager, Pablo and DeWard, Stephanie and Fulton, Anne and Gray, Kathryn J and Krall, Max and Mehta, Lakshmi and Rodan, Lance H and Saller, Devereux N and Steele, Deanna and Stein, Deborah and Yatsenko, Svetlana A and Bernier, Fran{\c c}ois P and Slavotinek, Anne M}
}
@article {1364504,
	title = {Kinetics and function of mesenchymal stem cells in corneal injury},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {7},
	year = {2012},
	month = {2012 Jun 14},
	pages = {3638-44},
	abstract = {PURPOSE: Bone marrow-derived mesenchymal stem cells (MSCs) hold great promise for wound healing and tissue regeneration. In the present study, we investigated the impact of corneal injury on the homeostasis of endogenous MSCs, and the potential of MSCs to home to injured tissue and promote corneal repair. METHODS: Corneal injury in mice was induced by thermal cauterization. Circulating MSCs were quantified by flow cytometric analysis. Ex vivo expanded red Q-dot-labeled or GFP+ bone marrow-derived MSCs were intravenously injected after injury and detected using epifluorescence microscopy. Corneal fluorescein staining was performed to evaluate epithelial regeneration. RESULTS: Following the induction of corneal injury in mice, a 2-fold increase in the frequency of circulating endogenous MSCs was observed within 48 hours of injury, which was accompanied by increased levels of the stem cell chemoattractants, substance P and SDF-1, in both the injured cornea and blood. Systemically administered MSCs homed to the injured cornea, but not to the normal cornea, and showed long-term survival. In addition, in the setting of corneal injury, MSC administration showed significant and rapid corneal epithelial regeneration. CONCLUSIONS: These findings provide novel evidence that corneal injury causes significant mobilization of endogenous MSCs into blood, and that MSCs home specifically to the injured cornea and promote regeneration, highlighting the therapeutic implications of MSC-mediated tissue repair in corneal injury.},
	keywords = {Animals, Bone Marrow Cells, Cell Differentiation, Cell Movement, Cell Survival, Cornea, Corneal Diseases, Corneal Injuries, Disease Models, Animal, Eye Injuries, Flow Cytometry, Follow-Up Studies, Male, Mesenchymal Stem Cells, Mice, Mice, Inbred C57BL, Stem Cell Transplantation, Wound Healing},
	issn = {1552-5783},
	doi = {10.1167/iovs.11-9311},
	author = {Lan, Yinan and Kodati, Shilpa and Lee, Hyun Soo and Omoto, Masahiro and Jin, Yiping and Chauhan, Sunil K}
}
@article {1016086,
	title = {A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear},
	journal = {Nat Biotechnol},
	volume = {35},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {280-284},
	abstract = {Efforts to develop gene therapies for hearing loss have been hampered by the lack of safe, efficient, and clinically relevant delivery modalities. Here we demonstrate the safety and efficiency of Anc80L65, a rationally designed synthetic vector, for transgene delivery to the mouse cochlea. Ex vivo transduction of mouse organotypic explants identified Anc80L65 from a set of other adeno-associated virus (AAV) vectors as a potent vector for the cochlear cell targets. Round window membrane injection resulted in highly efficient transduction of inner and outer hair cells in mice, a substantial improvement over conventional AAV vectors. Anc80L65 round window injection was well tolerated, as indicated by sensory cell function, hearing and vestibular function, and immunologic parameters. The ability of Anc80L65 to target outer hair cells at high rates, a requirement for restoration of complex auditory function, may enable future gene therapies for hearing and balance disorders.},
	issn = {1546-1696},
	doi = {10.1038/nbt.3781},
	author = {Landegger, Lukas D and Pan, Bifeng and Askew, Charles and Wassmer, Sarah J and Gluck, Sarah D and Galvin, Alice and Taylor, Ruth and Forge, Andrew and Stankovic, Konstantina M and Holt, Jeffrey R and Vandenberghe, Luk H}
}
@article {1651231,
	title = {Change in Ocular Surface Staining during Eyelid Warming Is Related to Tear Cytokine Levels},
	journal = {J Ophthalmol},
	year = {2022},
	author = {Landsend, ECS and Olafsson, J and Lai, X and Aass, HCD and Utheim, T P}
}
@article {1304384,
	title = {Meibomian gland dysfunction and keratopathy are associated with dry eye disease in aniridia},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {119-124},
	abstract = {AIMS: To investigate the aetiology and characteristics of dry eye disease (DED) in a Nordic cohort of patients with congenital aniridia. METHODS: Thirty-four Norwegian and one Danish subject with congenital aniridia and 21 healthy controls were examined. All subjects underwent an extensive dry eye examination, including evaluation of meibomian glands (MGs) by meibography, measurement of tear production and tear film osmolarity and grading of vital staining of the ocular surface. Moreover, slit-lamp biomicroscopy was undertaken, including grading of aniridia-associated keratopathy (AAK). RESULTS: Mean tear film osmolarity was significantly higher (314{\textpm}11 mOsmol/L) in patients with aniridia compared with the healthy control group (303{\textpm}11 mOsmol/L, p=0.002). Vital staining score was higher in the aniridia group (4.3{\textpm}3.0) compared with healthy controls (2.4{\textpm}1.6, p=0.02). The degree of staining correlated positively with the stage of AAK (r=0.44, p=0.008) and negatively with corneal sensitivity (r=-0.45, p=0.012). Number of expressible MGs was lower in aniridia subjects (2.9{\textpm}1.6) than in controls (4.0{\textpm}1.3, p=0.007). MG loss, staged from 0 to 3, was higher in the aniridia group than in the control group, both in upper eyelid (0.86{\textpm}0.89 vs 0.10{\textpm}0.31, p=0.001) and lower eyelid (0.94{\textpm}0.73 vs 0.30{\textpm}0.47, p=0.003). Computerised analyses showed thinning (p=0.004) and lower density (p\&lt;0.001) of the MGs compared with the healthy population. CONCLUSIONS: Patients with congenital aniridia demonstrate increased tear film osmolarity, ocular surface staining, loss of MGs and lower MG expressibility. We conclude that meibomian gland dysfunction and keratopathy are related to development of DED in aniridia.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2017-310927},
	author = {Landsend, Erlend Christoffer Sommer and Pedersen, Hilde R{\o}geberg and Utheim, {\O}ygunn Aass and Xiao, Jiaxin and Adil, Muhammed Yasin and Tashbayev, Behzod and Lagali, Neil and Dartt, Darlene Ann and Baraas, Rigmor C and Utheim, Tor Paaske}
}
@article {416966,
	title = {Long-term Risk of Melanoma-Related Mortality for Patients With Uveal Melanoma Treated With Proton Beam Therapy.},
	journal = {JAMA Ophthalmol},
	year = {2015},
	month = {2015 Apr 23},
	abstract = {Importance: Little is known about the long-term risk of dying of uveal melanoma after treatment with radiotherapy. Objective: To determine the long-term risk of dying of this disease, we evaluated melanoma-related mortality rates up to 25 years after proton beam therapy in a large series of patients with uveal melanoma. Design, Setting, and Participants: In this analysis, we included 3088 patients with uveal melanoma, identified from a hospital-based cohort and treated with proton irradiation between January 1975 and December 2005. Vital status and cause of death were ascertained through active follow-up and searches of government databases (the Social Security Death Index and the National Death Index) through December 31, 2008. Cumulative rates of melanoma-related mortality were calculated using the Kaplan-Meier method. Patient and tumor characteristics of known prognostic significance for melanoma-associated death were evaluated, including patient age and tumor dimensions. Main Outcomes and Measures: The primary outcome measure was cumulative rates of melanoma-specific mortality, and secondary measures included annual melanoma-specific mortality hazard rates and cumulative all-cause mortality rates. Results: Of 1490 deceased patients, 620 (41.6\%) died of ocular melanoma. In addition, 19 patients were alive, but their melanoma metastasized, by the end of the observation period (mean follow-up after diagnosis of metastasis, 5.3 years). All-cause mortality rates in this cohort were 49.0\% (95\% CI, 47.0-51.1) at 15 years, 58.6\% (95\% CI, 56.4\%-60.8\%) at 20 years, and 66.8\% (95\% CI, 64.2\%-69.4\%) at 25 years. Melanoma-related mortality rates were 24.6\% (95\% CI, 22.8-26.4) at 15 years after treatment, 25.8\% (95\% CI, 24.0-27.8) at 20 years after treatment, and 26.4\% (95\% CI, 24.5-28.5) at 25 years after treatment. The 20-year mortality rate was 8.6\% (95\% CI, 6.2-11.9) for younger patients (<=60 years) with small tumors (<=11 mm) and 40.1\% (95\% CI, 36.1-44.3) for older patients (\&gt;60 years) with large tumors (\&gt;11 mm). Conclusions and Relevance: In this large series of patients with ocular melanoma treated conservatively with proton beam irradiation, the cumulative melanoma-related mortality rates continued to increase up to 23 years after treatment. Annual rates decreased considerably (to \&lt;1\%) 14 years after treatment. Information regarding the long-term risk of dying of uveal melanoma may be useful to clinicians when counseling patients.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.0887},
	author = {Lane, Anne Marie and Kim, Ivana K and Gragoudas, Evangelos S}
}
@article {1016091,
	title = {LONG-TERM OUTCOMES OF RITUXIMAB THERAPY IN PATIENTS WITH NONINFECTIOUS POSTERIOR UVEITIS REFRACTORY TO CONVENTIONAL IMMUNOSUPPRESSIVE THERAPY},
	journal = {Retina},
	volume = {38},
	number = {2},
	year = {2018},
	month = {2018 Feb},
	pages = {395-402},
	abstract = {PURPOSE: To assess long-term effectiveness of rituximab therapy for refractory noninfectious uveitis affecting the posterior segment. METHODS: Retrospective case series. Patients diagnosed with recalcitrant noninfectious posterior uveitis who were treated with rituximab intravenous infusions between 2010 and 2015 were included. Patients underwent best-corrected visual acuity testing and fluorescein angiography evidence of disk or vascular staining at 6, 12, 18, and 24 months. Patients had at least 24 months of follow-up. RESULTS: Eleven patients (21 eyes) with refractory posterior uveitis treated with intravenous rituximab were included. Nine (81.8\%) patients were female. Mean follow-up was 29.3 {\textpm} 7.8 months. rituximab was administered as complementary therapy because of previous inefficacy of other therapies in 7 (63.7\%) patients, and it was the only treatment in four (36.3\%) patients who did not tolerate other drugs. Inflammation signs by fluorescein angiography were controlled in nine (81.8\%) patients at the end of follow-up. Baseline best-corrected visual acuity was 20/80 (logarithm of the minimal angle of resolution 0.6 {\textpm} 0.4), and final best-corrected visual acuity was 20/40 (0.3 {\textpm} 0.5) (P = 0.005). No significant side effects were reported. CONCLUSION: Rituximab therapy was associated with stability and remission of recalcitrant noninfectious posterior uveitis in patients who did not tolerate or did not respond to other therapies.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001563},
	author = {Lasave, Andres F and You, Caiyun and Ma, Lina and Abusamra, Khawla and Lamba, Neerav and Valdes Navarro, Manuel and Meese, Halea and Foster, C Stephen}
}
@article {1538312,
	title = {Changes in Corneal Subbasal Nerves after Punctal Occlusion in Dry Eye Disease},
	journal = {Curr Eye Res},
	volume = {46},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {777-783},
	abstract = {PURPOSE: To evaluate corneal subbasal nerve plexus by in vivo confocal microscopy (IVCM) following punctal occlusion in patients with moderate to severe dry eye disease (DED). MATERIALS AND METHODS: Patients with grade 3 or 4 severity of DED based on Delphi Panel dry eye severity grading scheme were enrolled in the study. Permanent inferior punctal occlusion was performed. A comprehensive ophthalmic evaluation, including Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal fluorescein staining, conjunctival Rose bengal staining, Schirmer{\textquoteright}s test, and corneal sensation by Cochet-Bonnet esthesiometry, were performed at baseline, and 1 and 3\&nbsp;months after punctal occlusion. Furthermore, density and number of corneal subbasal nerves were evaluated by IVCM. RESULTS: Forty-one eyes of 23 patients with a mean age of 46.3\&nbsp;{\textpm}\&nbsp;9.0\&nbsp;years were enrolled. Corneal fluorescein staining, Rose bengal staining, and TBUT significantly improved at 3\&nbsp;months following punctal occlusion (p \&lt;\&nbsp;.015). Corneal esthesiometry significantly increased at both postoperative visits (p \&lt;\&nbsp;.03), and OSDI scores improved only at 3-month follow-up (p \&lt;\&nbsp;.005). Nerve density and total number significantly increased 3\&nbsp;months after punctal occlusion (p \&lt;\&nbsp;.045). Baseline nerve density had significant correlations with TBUT, fluorescein staining, Rose bengal staining (p \&lt;\&nbsp;.012), but not with esthesiometry, Schirmer scores, or OSDI scores (p \&gt;\&nbsp;.329). CONCLUSIONS: Corneal subbasal nerve density and total number increased following punctal occlusion in patients with moderate to severe DED. These findings were associated with improvements in corneal sensation, and signs and symptoms of DED. This emphasizes the effect of punctal occlusion in regeneration of corneal subbasal nerve plexus.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2020.1833349},
	author = {Latifi, Golshan and Banafshe Afshan, Ali and Houshang Beheshtnejad, Amir and Zarei-Ghanavati, Mehran and Mohammadi, Neda and Ghaffari, Reza and Ghassemi, Hamed and Mohammadi, S Saeed and Kheirkhah, Ahmad}
}
@article {1328892,
	title = {Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration},
	journal = {Cell Rep},
	volume = {24},
	number = {7},
	year = {2018},
	month = {2018 Aug 14},
	pages = {1865-1879.e9},
	abstract = {We generated a knockout mouse for the neuronal-specific β-tubulin isoform Tubb3 to investigate its role in nervous system formation and maintenance. Tubb3 mice have no detectable neurobehavioral or neuropathological deficits, and upregulation of mRNA and protein of the remaining β-tubulin isotypes results in equivalent total β-tubulin levels in Tubb3 and wild-type mice. Despite similar levels of total β-tubulin, adult dorsal root ganglia lacking TUBB3 have decreased growth cone microtubule dynamics and a decreased neurite outgrowth rate of 22\% in\&nbsp;vitro and in\&nbsp;vivo. The effect of the 22\% slower growth rate is exacerbated for sensory recovery, where fibers must reinnervate the full volume of the skin to recover touch function. Overall, these data reveal that, while TUBB3 is not required for formation of the nervous system, it has a specific role in the rate of peripheral axon regeneration that cannot be replaced by other β-tubulins.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2018.07.029},
	author = {Latremoliere, Alban and Cheng, Long and DeLisle, Michelle and Wu, Chen and Chew, Sheena and Hutchinson, Elizabeth B and Sheridan, Andrew and Alexandre, Chloe and Latremoliere, Frederic and Sheu, Shu-Hsien and Golidy, Sara and Omura, Takao and Huebner, Eric A and Fan, Yanjie and Whitman, Mary C and Nguyen, Elaine and Hermawan, Crystal and Pierpaoli, Carlo and Tischfield, Max A and Woolf, Clifford J and Engle, Elizabeth C}
}
@article {1439852,
	title = {Genetic correlations between diabetes and glaucoma: an analysis of continuous and dichotomous phenotypes},
	journal = {Am J Ophthalmol},
	year = {2019},
	month = {2019 May 20},
	abstract = {PURPOSE: A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits. DESIGN: Cross-sectional study. METHODS: We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure (IOP), central corneal thickness (CCT), corneal hysteresis (CH), corneal resistance factor (CRF), cup-disc ratio (CDR), and primary open-angle glaucoma (POAG)). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank and the International Glaucoma Genetics Consortium. We calculated genetic correlation (r) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT and selected diabetes-related traits based on individual level phenotype data in two Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines (SOLAR). RESULTS: Overall, there was little r between diabetes- and glaucoma-related traits. Specifically, we found a non-significant negative correlation between T2D and POAG (r=-0.14; p=0.16). Using SOLAR, the genetic correlations between measured IOP, CCT, FBS, fasting insulin and hemoglobin A1c, were null. In contrast, genetic correlations between IOP and POAG (r >=0.45; p<=3.0E-04) and between CDR and POAG were high (r =0.57; p=2.8E-10). However, genetic correlations between corneal properties (CCT, CRF and CH) and POAG were low (r range: -0.18 - 0.11) and non-significant (p>=0.07). CONCLUSION: These analyses suggest there is limited genetic correlation between diabetes- and glaucoma-related traits.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.05.015},
	author = {Laville, Vincent and Kang, Jae H and Cousins, Clara C and Iglesias, Adriana I and Nagy, R{\'e}ka and Cooke Bailey, Jessica N and Igo, Robert P and Song, Yeunjoo E and Chasman, Daniel I and Christen, William G and Kraft, Peter and Rosner, Bernard A and Hu, Frank and Wilson, James F and Gharahkhani, Puya and Hewitt, Alex W and Mackey, David A and Hysi, Pirro G and Hammond, Christopher J and van Duijn, Cornelia M and Haines, Jonathan L and Vitart, Veronique and Fingert, John H and Hauser, Michael A and Aschard, Hugues and Wiggs, Janey L and Khawaja, Anthony P and Macgregor, Stuart and Pasquale, Louis R and UK Biobank, International Glaucoma Genetics Consortium, NEIGHBORHOOD Consortium}
}
@article {1664985,
	title = {Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	year = {2023},
	month = {2023 Jan 30},
	abstract = {PURPOSE: To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 {\texttimes} 6\&nbsp;mm and Montage 15 {\texttimes} 15\&nbsp;mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. RESULTS: Forty-eight RVLs were identified in 22 eyes (11.28\%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59\% vs. 3.95\%, P \&lt; 0.05). Type II RVLs accounted for a higher proportion than type I (89.58\% vs. 10.42\%, P \&lt; 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P \&lt; 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P \&lt; 0.05). CONCLUSION: WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.},
	issn = {1435-702X},
	doi = {10.1007/s00417-022-05957-3},
	author = {Le, Rongrong and Cui, Ying and Lu, Edward S and Zhu, Ying and Garg, Itika and Wang, Jay C and Lu, Yifan and Zeng, Rebecca and Katz, Raviv and La{\'\i}ns, In{\^e}s and Eliott, Dean and Husain, Deeba and Kim, Leo A and Miller, John B}
}
@article {635026,
	title = {Burn unit care of Stevens Johnson syndrome/toxic epidermal necrolysis: A survey.},
	journal = {Burns},
	volume = {42},
	number = {4},
	year = {2016},
	month = {2016 Jun},
	pages = {830-5},
	abstract = {Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a systemic disease that can be associated with debilitating acute and chronic complications across multiple organ systems. As patients with acute SJS/TEN are often treated in a burn intensive care unit (BICU), we surveyed burn centers across the United States to determine their approach to the care of these patients. The goal of our study was to identify best practices and possible variations in the care of patients with acute SJS/TEN. We demonstrate that the method of diagnosis, use of systemic therapies, and involvement of subspecialists varied significantly between burn centers. Beyond supportive care provided to every patient, our data highlights a lack of standardization in the acute care of patients with SJS/TEN. A comprehensive guideline for the care of patients with acute SJS/TEN is indicated.},
	issn = {1879-1409},
	doi = {10.1016/j.burns.2015.12.001},
	author = {Le, Hong-Gam and Saeed, Hajirah and Mantagos, Iason S and Mitchell, Caroline M and Goverman, Jeremy and Chodosh, James}
}
@article {1263356,
	title = {Management of Delayed Suprachoroidal Hemorrhage after Glaucoma Surgery},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 16},
	pages = {1-5},
	abstract = {PURPOSE: To review the most current treatment recommendations and outcomes for delayed suprachoroidal hemorrhages. METHODS: Article review of management and outcomes of suprachoroidal hemorrhages, with emphasis on delayed suprachoroidal hemorrhages in the setting of glaucoma surgery. CONCLUSION: Time of drainage of suprachoroidal hemorrhages remains controversial. Earlier drainage should be considered with high intraocular pressure, expulsion of intraocular content, or retinal detachment. In clinically stable eyes with suprachoroidal hemorrhage, recommendations range from observation to immediate drainage. Clot lysis occurs at roughly 14\&nbsp;days.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353814},
	author = {Learned, Daniel and Eliott, Dean}
}
@article {1439853,
	title = {Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity},
	journal = {FASEB J},
	volume = {33},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {9362-9373},
	abstract = {We have previously shown that knockdown of endomucin (EMCN), an integral membrane glycocalyx glycoprotein, prevents VEGF-induced proliferation, migration, and tube formation and angiogenesis . In the endothelium, VEGF mediates most of its angiogenic effects through VEGF receptor 2 (VEGFR2). To understand the role of EMCN, we examined the effect of EMCN depletion on VEGFR2 endocytosis and activation. Results showed that although VEGF stimulation promoted VEGFR2 internalization in control endothelial cells (ECs), loss of EMCN prevented VEGFR2 endocytosis. Cell surface analysis revealed a decrease in VEGFR2 following VEGF stimulation in control but not siRNA directed against EMCN-transfected ECs. EMCN depletion resulted in heightened phosphorylation following VEGF stimulation with an increase in total VEGFR2 protein. These results indicate that EMCN modulates VEGFR2 endocytosis and activity and point to EMCN as a potential therapeutic target.-LeBlanc, M. E., Saez-Torres, K. L., Cano, I., Hu, Z., Saint-Geniez, M., Ng, Y.-S., D{\textquoteright}Amore, P. A. Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity.},
	issn = {1530-6860},
	doi = {10.1096/fj.201900011R},
	author = {LeBlanc, Michelle E and Saez-Torres, Kahira L and Cano, Issahy and Hu, Zhengping and Saint-Geniez, Magali and Ng, Yin-Shan and D{\textquoteright}Amore, Patricia A}
}
@article {1302171,
	title = {Transferable vancomycin resistance in clade B commensal-type Enterococcus faecium},
	journal = {J Antimicrob Chemother},
	volume = {73},
	number = {6},
	year = {2018},
	month = {2018 Jun 01},
	pages = {1479-1486},
	abstract = {Objectives: Vancomycin-resistant Enterococcus faecium is a leading cause of MDR hospital infection. Two genetically definable populations of E. faecium have been identified: hospital-adapted MDR isolates (clade A) and vancomycin-susceptible commensal strains (clade B). VanN-type vancomycin resistance was identified in two isolates of E. faecium recovered from blood and faeces of an immunocompromised patient. To understand the genomic context in which VanN occurred in the hospitalized patient, the risk it posed for transmission in the hospital and its origins, it was of interest to determine where these strains placed within the E. faecium population structure.

Methods: We obtained the genome sequence of the VanN isolates and performed comparative and functional genomics of the chromosome and plasmid content.

Results: We show that, in these strains, VanN occurs in a genetic background that clusters with clade B E. faecium, which is highly unusual. We characterized the chromosome and the conjugative plasmid that carries VanN resistance in these strains, pUV24. This plasmid exhibits signatures of in-host selection on the vanN operon regulatory system, which are associated with a constitutive expression of vancomycin resistance. VanN resistance in clade B strains may go undetected by current methods.

Conclusions: We report a case of vancomycin resistance in a commensal lineage of E. faecium responsible for an atypical bacteraemia in an immunocompromised patient. A reservoir of transferable glycopeptide resistance in the community could pose a concern for public health.},
	issn = {1460-2091},
	doi = {10.1093/jac/dky039},
	author = {Lebreton, Fran{\c c}ois and Valentino, Michael D and Schaufler, Katharina and Earl, Ashlee M and Cattoir, Vincent and Gilmore, Michael S}
}
@article {1363136,
	title = {High-Quality Draft Genome Sequence of Vagococcus lutrae Strain LBD1, Isolated from the Largemouth Bass Micropterus salmoides},
	journal = {Genome Announc},
	volume = {1},
	number = {6},
	year = {2013},
	month = {2013 Dec 26},
	abstract = {Vagococci are usually isolated from marine hosts and occasionally from endodontic infections. Using 16S rRNA gene comparison, the closest relatives are members of the genera Enterococcus and Carnobacterium. A draft sequence of Vagococcus lutrae was generated to clarify the relationship of Vagococcus to these and other related low-G+C Gram-positive bacteria.},
	issn = {2169-8287},
	doi = {10.1128/genomeA.01087-13},
	author = {Lebreton, Fran{\c c}ois and Valentino, Michael D and Duncan, Lucile B and Zeng, Qiandong and McGuire, Abigail Manson and Earl, Ashlee M and Gilmore, Michael S}
}
@article {1078776,
	title = {Tracing the Enterococci from Paleozoic Origins to the Hospital},
	journal = {Cell},
	volume = {169},
	number = {5},
	year = {2017},
	month = {2017 May 18},
	pages = {849-861.e13},
	abstract = {We examined the evolutionary history of leading multidrug resistant hospital pathogens, the enterococci, to their origin hundreds of millions of years ago. Our goal was to understand why, among the vast diversity of gut flora, enterococci are so well adapted to the modern hospital environment. Molecular clock estimation, together with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, place the origins of the enterococci around the time of animal terrestrialization, 425-500 mya. Speciation appears to parallel the diversification of hosts, including the rapid emergence of new enterococcal species following the End Permian Extinction. Major drivers of speciation include changing carbohydrate availability in the host gut. Life on land would have selected for the precise traits that now allow pathogenic enterococci to survive desiccation, starvation, and disinfection in the modern hospital, foreordaining their emergence as leading hospital pathogens.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2017.04.027},
	author = {Lebreton, Fran{\c c}ois and Manson, Abigail L and Saavedra, Jose T and Straub, Timothy J and Earl, Ashlee M and Gilmore, Michael S}
}
@article {1363137,
	title = {Emergence of epidemic multidrug-resistant Enterococcus faecium from animal and commensal strains},
	journal = {MBio},
	volume = {4},
	number = {4},
	year = {2013},
	month = {2013 Aug 20},
	abstract = {UNLABELLED: Enterococcus faecium, natively a gut commensal organism, emerged as a leading cause of multidrug-resistant hospital-acquired infection in the 1980s. As the living record of its adaptation to changes in habitat, we sequenced the genomes of 51 strains, isolated from various ecological environments, to understand how E. faecium emerged as a leading hospital pathogen. Because of the scale and diversity of the sampled strains, we were able to resolve the lineage responsible for epidemic, multidrug-resistant human infection from other strains and to measure the evolutionary distances between groups. We found that the epidemic hospital-adapted lineage is rapidly evolving and emerged approximately 75 years ago, concomitant with the introduction of antibiotics, from a population that included the majority of animal strains, and not from human commensal lines. We further found that the lineage that included most strains of animal origin diverged from the main human commensal line approximately 3,000 years ago, a time that corresponds to increasing urbanization of humans, development of hygienic practices, and domestication of animals, which we speculate contributed to their ecological separation. Each bifurcation was accompanied by the acquisition of new metabolic capabilities and colonization traits on mobile elements and the loss of function and genome remodeling associated with mobile element insertion and movement. As a result, diversity within the species, in terms of sequence divergence as well as gene content, spans a range usually associated with speciation. IMPORTANCE: Enterococci, in particular vancomycin-resistant Enterococcus faecium, recently emerged as a leading cause of hospital-acquired infection worldwide. In this study, we examined genome sequence data to understand the bacterial adaptations that accompanied this transformation from microbes that existed for eons as members of host microbiota. We observed changes in the genomes that paralleled changes in human behavior. An initial bifurcation within the species appears to have occurred at a time that corresponds to the urbanization of humans and domestication of animals, and a more recent bifurcation parallels the introduction of antibiotics in medicine and agriculture. In response to the opportunity to fill niches associated with changes in human activity, a rapidly evolving lineage emerged, a lineage responsible for the vast majority of multidrug-resistant E. faecium infections.},
	keywords = {Animals, Cluster Analysis, Cross Infection, DNA, Bacterial, Drug Resistance, Multiple, Bacterial, Enterococcus faecium, EPIDEMICS, Evolution, Molecular, Genome, Bacterial, Gram-Positive Bacterial Infections, Humans, Phylogeny, Sequence Analysis, DNA},
	issn = {2150-7511},
	doi = {10.1128/mBio.00534-13},
	author = {Lebreton, Fran{\c c}ois and van Schaik, Willem and McGuire, Abigail Manson and Godfrey, Paul and Griggs, Allison and Mazumdar, Varun and Corander, Jukka and Cheng, Lu and Saif, Sakina and Young, Sarah and Zeng, Qiandong and Wortman, Jennifer and Birren, Bruce and Willems, Rob J L and Earl, Ashlee M and Gilmore, Michael S}
}
@article {1814366,
	title = {A recurrent missense variant in the E3 ubiquitin ligase substrate recognition subunit FEM1B causes a rare syndromic neurodevelopmental disorder},
	journal = {Genet Med},
	year = {2024},
	month = {2024 Mar 07},
	pages = {101119},
	abstract = {PURPOSE: FEM1B acts as a substrate recognition subunit for ubiquitin ligase complexes belonging to the CRL2 E3 family. Several biological functions have been proposed for FEM1B, including a structurally resolved function as a sensor for redox cell status by controlling mitochondrial activity, but its implication in human disease remains elusive. METHODS: To understand the involvement of FEM1B in human disease, we made use of Matchmaker exchange platforms to identify individuals with de novo variants in FEM1B and performed their clinical evaluation. We performed functional validation using primary neuronal cultures and in-utero electroporation assays, as well as experiments on patient{\textquoteright}s cells. RESULTS: Five individuals with a recurrent de novo missense variant in FEM1B were identified: NM_015322.5:c.377G\&gt;A NP_056137.1:p.(Arg126Gln) (FEM1BR126Q). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells. In addition, the individuals{\textquoteright} cells exhibited signs of oxidative stress and induction of type I interferon signaling. CONCLUSION: Overall, our data indicate that p.(Arg126Gln) induces aberrant FEM1B activation resulting in a gain-of-function mechanism associated with a severe syndromic developmental disorder in humans.},
	issn = {1530-0366},
	doi = {10.1016/j.gim.2024.101119},
	author = {Lecoquierre, Fran{\c c}ois and Punt, A Mattijs and Ebstein, Fr{\'e}d{\'e}ric and Wallaard, Ilse and Verhagen, Rob and Studencka-Turski, Maja and Duffourd, Yannis and Moutton, S{\'e}bastien and Tran Mau-Them, Fr{\'e}d{\'e}dic and Philippe, Christophe and Dean, John and Tennant, Stephen and Brooks, Alice S and van Slegtenhorst, Marjon A and Jurgens, Julie A and Barry, Brenda J and Chan, Wai-Man and England, Eleina M and Martinez Ojeda, Mayra and Engle, Elizabeth C and Robson, Caroline D and Morrow, Michelle and Innes, A Micheil and Lamont, Ryan and Sanderson, Matthea and Kr{\"u}ger, Elke and Thauvin, Christel and Distel, Ben and Faivre, Laurence and Elgersma, Ype and Vitobello, Antonio}
}
@article {1307448,
	title = {Determinants of Outcomes of Adenoviral Keratoconjunctivitis},
	journal = {Ophthalmology},
	volume = {125},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {1344-1353},
	abstract = {PURPOSE: To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. DESIGN: Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694). PARTICIPANTS: Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus. METHODS: Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression. MAIN OUTCOME MEASURES: The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign. RESULTS: Of 500 participants, 390 (78\%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63\% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non-adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age. CONCLUSIONS: A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non-adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.02.016},
	author = {Lee, Cecilia S and Lee, Aaron Y and Akileswaran, Lakshmi and Stroman, David and Najafi-Tagol, Kathryn and Kleiboeker, Steve and Chodosh, James and Magaret, Amalia and Wald, Anna and Van Gelder, Russell N and BAYnovation Study Group}
}
@article {1798381,
	title = {The influence of orbital architecture on strabismus in craniosynostosis},
	journal = {J AAPOS},
	volume = {28},
	number = {1},
	year = {2024},
	month = {2024 Feb},
	pages = {103812},
	abstract = {PURPOSE: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis.

METHODS: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children{\textquoteright}s Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements.

RESULTS: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63\%), Crouzon syndrome (13\%), Apert syndrome (13\%), and Pfeiffer syndrome (10\%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups.

CONCLUSIONS: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width~and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.},
	keywords = {Acrocephalosyndactylia, Case-Control Studies, Child, Craniosynostoses, Humans, Orbit, Retrospective Studies, Strabismus},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.10.006},
	author = {Lee, Tonya C and Walker, Evan and Ting, Michelle A and Bolar, Divya S and Koning, Jeffrey and Korn, Bobby S and Kikkawa, Don O and Granet, David and Robbins, Shira L and Alperin, Marianna and Engle, Elizabeth C and Liu, Catherine Y and Rudell, Jolene C}
}
@article {313176,
	title = {Ischemic diabetic retinopathy as a possible prognostic factor for chronic kidney disease progression},
	journal = {Eye (Lond)},
	volume = {28},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1119-25},
	abstract = {PURPOSE: To assess the value of diabetic retinopathy (DR) severity as a possible predictive prognostic factor for the progression of chronic kidney disease (CKD). PATIENTS AND METHODS: Retrospective cohort study. Patients (51) who were initially diagnosed with DR and CKD were enrolled and their medical records were evaluated. The following ophthalmic factors were assessed by fluorescein angiography at the initial visit: area of capillary nonperfusion, presence of neovascularization and vitreous hemorrhage, and DR grade. The effect of these factors on CKD progression over the 2-year period of the study, defined as doubling of serum creatinine or the development of end-stage renal disease requiring dialysis or renal transplant, was evaluated. RESULTS: The study included 51 patients with DR and CKD; of these, 11 patients (21.6\%) were found to have proliferative DR (PDR) and seven patients (13.7\%) had high-risk PDR at baseline. Patients with ischemic DR, who showed extensive capillary nonperfusion (>= 10 optic disc areas) in the retina, had a greater risk for CKD progression (hazard ratio = 6.64; P = 0.002). CONCLUSION: We found that extensive capillary nonperfusion in the retina greatly increased the risk of progression of CKD in patients with DR. This suggests that the retina and the kidney may have shared risk factors for microvascular disease secondary to diabetes mellitus, and emphasizes the need for a team approach to diabetes care.},
	keywords = {Adult, Aged, Cohort Studies, Creatinine, Diabetic Retinopathy, Disease Progression, Female, Fluorescein Angiography, Glomerular Filtration Rate, Humans, Ischemia, Kidney Failure, Chronic, Kidney Transplantation, Male, Middle Aged, Prognosis, Renal Insufficiency, Chronic, Retinal Neovascularization, Retinal Vessels, Retrospective Studies, Risk Factors, Vitreous Hemorrhage},
	issn = {1476-5454},
	doi = {10.1038/eye.2014.130},
	author = {Lee, W J and Sobrin, L and Kang, M H and Seong, M and Kim, Y J and Yi, J-H and Miller, J W and Cho, H Y}
}
@article {1405413,
	title = {The Relationship Between Optic Disc Parameters and Female Reproductive Factors in Young Women},
	journal = {Asia Pac J Ophthalmol (Phila)},
	year = {2018},
	month = {2018 Dec 31},
	abstract = {PURPOSE: It has been suggested that female sex steroids have neuroprotective properties that may reduce risk of glaucoma in premenopausal women. In this study, we explored the associations of optic disc measures with female reproductive factors in a population of young women. DESIGN: Cohort study. METHODS: Young women (n = 494; age range, 18-22 years) were recruited as part of the Western Australian Pregnancy Cohort (Raine) Study. Information on age at menarche, parity, and use of hormonal contraceptives were obtained from questionnaires. Participants underwent an eye examination, including spectral-domain optical coherence tomography imaging, to obtain optic disc parameters. RESULTS: Women who had given birth at least once (parous women; n = 10) had larger vertical neuroretinal rim widths ( \&lt; 0.001) than nulliparous women (n = 484) after correcting for use of hormonal contraceptives, intraocular pressure, refractive error, and family history of glaucoma. Furthermore, vertical and horizontal cup-to-disc ratios, which are inherently related to neuroretinal rim width, were found to be smaller among parous women compared with nulliparous women (both \&lt; 0.001). Age at menarche and use of hormonal contraceptives were not significantly associated with any optic disc parameters. CONCLUSIONS: We found limited evidence that female reproductive factors were related with optic disc parameters during young adulthood. The association between parity and optic disc parameter, though significant, should be further investigated given the small number of parous women in the current sample. Future follow-ups of this cohort will allow us to explore for any associations of these factors with optic disc parameters and glaucoma risk at an older age.},
	issn = {2162-0989},
	doi = {10.22608/APO.2018329},
	author = {Lee, Samantha S Y and Yazar, Seyhan and Pasquale, Louis R and Sanfilippo, Paul G and Hewitt, Alex W and Hickey, Martha and Skinner, Rachel and Mackey, David A}
}
@article {959441,
	title = {MC5r and A2Ar Deficiencies During Experimental Autoimmune Uveitis Identifies Distinct T cell Polarization Programs and a Biphasic Regulatory Response.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016 Nov 25},
	pages = {37790},
	abstract = {Autoantigen-specific regulatory immunity emerges in the spleen of mice recovering from experimental autoimmune uveitis (EAU), a murine model for human autoimmune uveoretinitis. This regulatory immunity provides induced tolerance to ocular autoantigen, and requires melanocortin 5 receptor (MC5r) expression on antigen presenting cells with adenosine 2 A receptor (A2Ar) expression on T cells. During EAU it is not well understood what roles MC5r and A2Ar have on promoting regulatory immunity. Cytokine profile analysis during EAU revealed MC5r and A2Ar each mediate distinct T cell responses, and are responsible for a functional regulatory immune response in the spleen. A2Ar stimulation at EAU onset did not augment this regulatory response, nor bypass the MC5r requirement to induce regulatory immunity. The importance of this pathway in human autoimmune uveitis was assayed. PBMC from uveitis patients were assayed for MC5r expression on monocytes and A2Ar on T cells, and comparison between uveitis patients and healthy controls had no significant difference. The importance for MC5r and A2Ar expression in EAU to promote the induction of protective regulatory immunity, and the expression of MC5r and A2Ar on human immune cells, suggests that it may be possible to utilize the melanocortin-adenosinergic pathways to induce protective immunity in uveitic patients.},
	issn = {2045-2322},
	doi = {10.1038/srep37790},
	author = {Lee, Darren J and Preble, Janine and Lee, Stacey and Foster, C Stephen and Taylor, Andrew W}
}
@article {1603862,
	title = {Corneal lymphangiogenesis in dry eye disease is regulated by substance P/neurokinin-1 receptor system through controlling expression of vascular endothelial growth factor receptor 3},
	journal = {Ocul Surf},
	volume = {22},
	year = {2021},
	month = {2021 Jul 24},
	pages = {72-79},
	abstract = {PURPOSE: To evaluate the role of substance P (SP)/neurokinin-1 receptor (NK1R) system in the regulation of pathologic corneal lymphangiogenesis in dry eye disease (DED). METHODS: Immunocytochemistry, angiogenesis assay, and Western blot analysis of human dermal lymphatic endothelial cells (HDLECs) were conducted to assess the involvement of SP/NK1R system in lymphangiogenesis. DED was induced in wild-type C57BL/6\&nbsp;J mice using controlled-environment chamber without scopolamine. Immunohistochemistry, corneal fluorescein staining, and phenol red thread test were used to evaluate the effect of SP signaling blockade in the corneal lymphangiogenesis. The expression of lymphangiogenic factors in the corneal and conjunctival tissues of DED mouse model was quantified by real-time polymerase chain reaction. RESULTS: NK1R expression and pro-lymphangiogenic property of SP/NK1R system in HDLECs were confirmed by Western blot analysis and angiogenesis assay. Blockade of SP signaling with L733,060, an antagonist of NK1R, or NK1R-targeted siRNA significantly inhibited lymphangiogenesis and expression of vascular endothelial growth factor (VEGF) receptor 3 stimulated by SP in HDLECs. NK1R antagonist also suppressed pathological corneal lymphangiogenesis and ameliorated the clinical signs of dry eye in vivo. Furthermore, NK1R antagonist effectively suppressed the lymphangiogenic factors, including VEGF-C, VEGF-D, and VEGF receptor 3 in the corneal and conjunctival tissues of DED. CONCLUSIONS: SP/NK1R system promotes lymphangiogenesis in vitro and NK1R antagonism suppresses pathologic corneal lymphangiogenesis in DED in vivo.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.07.003},
	author = {Lee, Seok Jae and Kim, Sang-Tae and Wu, Jun and Cho, Chang Sik and Jo, Dong Hyun and Chen, Yihe and Dana, Reza and Kim, Jeong Hun and Lee, Sang-Mok}
}
@article {1655712,
	title = {Therapeutic roles of PPARα activation in ocular ischemic diseases},
	journal = {Histol Histopathol},
	volume = {38},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {391-401},
	abstract = {Ocular ischemia is one of the leading causes of blindness. It is related to various ocular diseases and disorders, including age-related macular degeneration, diabetic retinopathy, glaucoma, and corneal injury. Ocular ischemia occurs due to an abnormal supply of oxygen and nutrients to the eye, resulting in ocular metabolic dysfunction. These changes can be linked with pathologic conditions in the eye, such as inflammation, neovascularization, and cell death, ultimately leading to vision loss. The current treatment care for ocular ischemia is limited. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor protein functioning in regulating lipid metabolism, fatty acid oxidation, and glucose homeostasis. Recently, PPARα activation has been suggested as a useful therapeutic target in treating ocular ischemia. However, its applications have not been well summarized. In this review, we cover an overview of the therapeutic roles of PPARα activation in various ocular ischemic conditions with recent experimental evidence and further provide clinical implications of its therapeutic applications. Our review will enable more approaches to comprehensively understand the therapeutic roles of PPARα activation for preventing ocular ischemic diseases.},
	keywords = {Diabetic Retinopathy, Humans, Ischemia, Macular Degeneration, Neovascularization, Pathologic, PPAR alpha},
	issn = {1699-5848},
	doi = {10.14670/HH-18-542},
	author = {Lee, Deokho and Tomita, Yohei and Negishi, Kazuno and Kurihara, Toshihide}
}
@article {1478322,
	title = {Punctal stenosis associated with dupilumab therapy for atopic dermatitis},
	journal = {J Dermatolog Treat},
	volume = {32},
	number = {7},
	year = {2021},
	month = {2021 Nov},
	pages = {737-740},
	abstract = {In this case series, the authors report three patients with severe atopic dermatitis who presented with epiphora and conjunctivitis while undergoing dupilumab therapy. On clinical examination, all patients were found to have punctal stenosis, with one case having progressed to punctal obstruction. An assortment of strategies was elected, including discontinuation of dupilumab, treatment of conjunctivitis, and surgical intervention with probing, punctoplasty, and silicone intubation. This report spotlights punctal stenosis as an important new side effect of dupilumab and suggests that additional cases of dupilumab-associated lacrimal drainage impairment will continue to emerge.},
	keywords = {Antibodies, Monoclonal, Humanized, Constriction, Pathologic, Dacryocystorhinostomy, Dermatitis, Atopic, Humans, Intubation, Lacrimal Duct Obstruction, Retrospective Studies},
	issn = {1471-1753},
	doi = {10.1080/09546634.2019.1711010},
	author = {Lee, Debora H and Cohen, Liza M and Yoon, Michael K and Tao, Jeremiah P}
}
@article {1363139,
	title = {Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process},
	journal = {PLoS One},
	volume = {8},
	number = {9},
	year = {2013},
	month = {2013},
	pages = {e75769},
	abstract = {A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 {\textmu}g) versus hi-dose (1000 {\textmu}g) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.},
	keywords = {Animals, Antigens, Cell Proliferation, Cytokines, Eosinophils, Forkhead Transcription Factors, Hypersensitivity, Immunization, Immunoglobulin E, Interleukin-2 Receptor alpha Subunit, Male, Mice, Mice, Inbred C57BL, Ovalbumin, T-Lymphocytes, Regulatory, Th2 Cells, Transforming Growth Factor beta},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0075769},
	author = {Lee, Hyun Soo and Schlereth, Simona and Khandelwal, Payal and Saban, Daniel R}
}
@article {280861,
	title = {The relationship between diabetic retinopathy and diabetic nephropathy in a population-based study in Korea (KNHANES V-2,3).},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2014},
	month = {2014 Sep 9},
	abstract = {PURPOSE. To determine the risk factors for and relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN), including microalbuminuria and overt nephropathy, in a population-based study of diabetes mellitus (DM) patients in Korea. METHODS. This was a population-based, cross-sectional study. From the fifth (2011, 2012) Korea National Health and Nutrition Examination Survey (KNHANES), 971 participants with type 2 DM were included. The prevalence of DR and DN was determined. Multivariate logistic regression was performed to determine risk factors, including DR, associated with DN in the Korean population. RESULTS. In DM patients, we observed a prevalence of 20.0\% for any DR and 3.8\% for proliferative diabetic retinopathy (PDR). Microalbuminuria prevalence was 19.3\% and overt nephropathy prevalence was 5.5\%. The risk factors of microalbuminuria were presence of hypertension, higher systolic blood pressure, serum hemoglobin A1c (HbA1c) and serum blood urea nitrogen level as well as the presence of PDR. The risk factors of overt nephropathy were long duration of DM, high levels of HbA1c, systolic blood pressure, total cholesterol and serum creatinine as well as the presence of DR. CONCLUSIONS. PDR is associated with microalbuminuria and DR is associated with overt nephropathy in Korean DM patients. Our findings suggest that when an ophthalmologist finds the presence of DR or PDR, timely evaluation of the patient{\textquoteright}s renal status should be recommended.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15001},
	author = {Lee, Won June and Sobrin, Lucia and Lee, Min Jeong and Kang, Min Ho and Seong, Mincheol and Cho, Heeyoon}
}
@article {1528418,
	title = {Entry of Epidemic Keratoconjunctivitis-Associated Human Adenovirus Type 37 in Human Corneal Epithelial Cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {10},
	year = {2020},
	month = {2020 Aug 03},
	pages = {50},
	abstract = {Purpose: Ocular infection by human adenovirus species D type 37 (HAdV-D37) causes epidemic keratoconjunctivitis, a severe, hyperacute condition. The corneal component of epidemic keratoconjunctivitis begins upon infection of corneal epithelium, and the mechanism of viral entry dictates subsequent proinflammatory gene expression. Therefore, it is important to understand the specific pathways of adenoviral entry in these cells. Methods: Transmission electron microscopy of primary and tert-immortalized human corneal epithelial cells infected with HAdV-D37 was performed to identify the means of viral entry. Confocal microscopy was used to determine intracellular trafficking. The results of targeted small interfering RNA and specific chemical inhibitors were analyzed by quantitative PCR, and Western blot. Results: By transmission electron microscopy, HAdV-D37 was seen to enter by both clathrin-coated pits and macropinocytosis; however, entry was both pH and dynamin 2 independent. Small interfering RNA against clathrin, AP2A1, and lysosome-associated membrane protein 1, but not early endosome antigen 1, decreased early viral gene expression. Ethyl-isopropyl amiloride, which blocks micropinocytosis, did not affect HAdV-D37 entry, but IPA, an inhibitor of p21-activated kinase, and important to actin polymerization, decreased viral entry in a dose-dependent manner. Conclusions: HAdV-D37 enters human corneal epithelial cells by a noncanonical clathrin-mediated pathway involving lysosome-associated membrane protein 1 and PAK1, independent of pH, dynamin, and early endosome antigen 1. We showed earlier that HAdV-D37 enters human keratocytes through caveolae. Therefore, epidemic keratoconjunctivitis-associated viruses enter different corneal cell types via disparate pathways, which could account for a relative paucity of proinflammatory gene expression upon infection of corneal epithelial cells compared with keratocytes, as seen in prior studies.},
	issn = {1552-5783},
	doi = {10.1167/iovs.61.10.50},
	author = {Lee, Ji Sun and Mukherjee, Santanu and Lee, Jeong Yoon and Saha, Amrita and Chodosh, James and Painter, David F and Rajaiya, Jaya}
}
@article {1319471,
	title = {Bacterial RecA Protein Promotes Adenoviral Recombination during Infection},
	journal = {mSphere},
	volume = {3},
	number = {3},
	year = {2018},
	month = {2018 Jun 27},
	abstract = {Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi, were identified immediately 5{\textquoteright} to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an lysate increased recombination; this was blocked in a RecA mutant strain, DH5α, or upon RecA depletion. Recombination increased in the presence of lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.},
	issn = {2379-5042},
	doi = {10.1128/mSphere.00105-18},
	author = {Lee, Jeong Yoon and Lee, Ji Sun and Materne, Emma C and Rajala, Rahul and Ismail, Ashrafali M and Seto, Donald and Dyer, David W and Rajaiya, Jaya and Chodosh, James}
}
@article {1653577,
	title = {Retinal degeneration induced in a mouse model of ischemia-reperfusion injury and its management by pemafibrate treatment},
	journal = {FASEB J},
	volume = {36},
	number = {9},
	year = {2022},
	month = {2022 09},
	pages = {e22497},
	abstract = {Retinal ischemia-reperfusion (I/R) injury is a common cause of visual impairment. To date, no effective treatment is available for retinal I/R injury. In addition, the precise pathological mechanisms still need to be established. Recently, pemafibrate, a peroxisome proliferator-activated receptor α (PPARα) modulator, was shown to be a promising drug for retinal ischemia. However, the role of pemafibrate in preventing retinal I/R injury has not been documented. Here, we investigated how retinal degeneration occurs in a mouse model of retinal I/R injury by elevation of intraocular pressure and examined whether pemafibrate could be beneficial against retinal degeneration. Adult mice were orally administered pemafibrate (0.5\&nbsp;mg/kg/day) for 4 days, followed by retinal I/R injury. The mice were continuously administered pemafibrate once every day until the end of the experiments. Retinal functional changes were measured using electroretinography. Retina, liver, and serum samples were used for western blotting, quantitative PCR, immunohistochemistry, or enzyme linked immunosorbent assay. Retinal degeneration induced by retinal inflammation was prevented by pemafibrate administration. Pemafibrate administration increased the hepatic PPARα target gene expression and serum levels of fibroblast growth factor 21, a neuroprotective molecule in the eye. The expression of hypoxia-response and pro-and anti-apoptotic/inflammatory genes increased in the retina following retinal I/R injury; however, these changes were modulated by pemafibrate administration. In conclusion, pemafibrate is a promising preventive drug for ischemic retinopathies.},
	keywords = {Animals, Benzoxazoles, Butyrates, Disease Models, Animal, Ischemia, Mice, PPAR alpha, Reperfusion Injury, Retinal Degeneration},
	issn = {1530-6860},
	doi = {10.1096/fj.202200455RRR},
	author = {Lee, Deokho and Nakai, Ayaka and Miwa, Yukihiro and Tomita, Yohei and Kunimi, Hiromitsu and Chen, Junhan and Ikeda, Shin-Ichi and Tsubota, Kazuo and Negishi, Kazuno and Kurihara, Toshihide}
}
@article {1318867,
	title = {Hypoxia modulates the development of a corneal stromal matrix model},
	journal = {Exp Eye Res},
	volume = {170},
	year = {2018},
	month = {2018 May},
	pages = {127-137},
	abstract = {Deposition of matrix proteins during development and repair is critical to the transparency of the cornea. While many cells respond to a hypoxic state that can occur in a tumor, the cornea is exposed to hypoxia during development prior to eyelid opening and during the diurnal sleep cycle where oxygen levels can drop from 21\% to 8\%. In this study, we used 2 three-dimensional (3-D) models to examine how stromal cells respond to periods of acute hypoxic states. The first model, a stromal construct model, is a 3-D stroma-like construct that consists of human corneal fibroblasts (HCFs) stimulated by a stable form of ascorbate for 1, 2, and 4 weeks to self-assemble their own extracellular matrix. The second model, a corneal organ culture model, is a corneal wound-healing model, which consists of wounded adult rat corneas that were removed and placed in culture to heal. Both models were exposed to either normoxic or hypoxic conditions for varying time periods, and the expression and/or localization of matrix proteins was assessed. No significant changes were detected in Type V collagen, which is associated with Type I collagen fibrils; however, significant changes were detected in the expression of both the small leucine-rich repeating proteoglycans and the larger heparan sulfate proteoglycan, perlecan. Also, hypoxia decreased both the number of Cuprolinic blue-positive glycosaminoglycan chains along collagen fibrils and Sulfatase 1, which modulates the effect of heparan sulfate by removing the 6-O-sulfate groups. In the stromal construct model, alterations were seen in fibronectin, similar to those that occur in development and after injury. These changes in fibronectin after injury were accompanied by changes in proteoglycans. Together these findings indicate that acute hypoxic changes alter the physiology of the cornea, and these models will allow us to manipulate the conditions in the extracellular environment in order to study corneal development and trauma.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.02.021},
	author = {Lee, Albert and Karamichos, Dimitrios and Onochie, Obianamma E and Hutcheon, Audrey E K and Rich, Celeste B and Zieske, James D and Trinkaus-Randall, Vickery}
}
@article {1667690,
	title = {Utility of In Vivo Confocal Microscopy in Diagnosis of Acanthamoeba Keratitis: A Comparison of Patient Outcomes},
	journal = {Cornea},
	volume = {42},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {135-140},
	abstract = {PURPOSE: The aim of this study was to compare outcomes between cases of Acanthamoeba keratitis (AK) diagnosed and treated with or without the use of in vivo confocal microscopy (IVCM). METHODS: We performed a retrospective comparative case series of 26 eyes of 23 patients diagnosed with AK at the Massachusetts Eye and Ear Infirmary over a 5-year period. The characteristics of all identified cases were summarized. We compared the time from presentation to diagnosis of AK (primary outcome), visual acuity, and rates of therapeutic penetrating keratoplasty between eyes diagnosed by culture-only group (n = 8) and by IVCM to diagnose AK (n = 9) and later confirmed by culture (IVCM/C group). RESULTS: The diagnostic delay was significantly longer in the culture only group (25 {\textpm} 29 days) compared with the IVCM/C group (3 {\textpm} 3 days, P \&lt; 0.01). At 6 months, there was a significant difference in best-corrected visual acuity between the culture-only group (1.46 {\textpm} 1.07, n = 7) and the IVCM/C group (0.22 {\textpm} 0.22, n = 8), after adjusting for initial baseline visual acuity (P = 0.02). Therapeutic penetrating keratoplasty was performed in 50\% of culture-only (n = 7) and 11\% of IVCM/C group eyes (n = 9), but this was not statistically significant (P = 0.13). CONCLUSIONS: IVCM can expedite the diagnosis of AK, and its use as an adjunct tool in the diagnosis of AK may result in better patient outcomes compared with basing treatment decisions on corneal cultures alone.},
	keywords = {Acanthamoeba Keratitis, Cornea, Delayed Diagnosis, Humans, Microscopy, Confocal, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003184},
	author = {Lee, Hyunjoo J and Alipour, Fateme and Cruzat, Andrea and Posarelli, Matteo and Zheng, Lixin and Hamrah, Pedram}
}
@article {1363140,
	title = {The role of genetics in the pathogenesis of periocular cutaneous neoplasms: implications for targeted therapy},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {267-74},
	abstract = {In the past, cutaneous malignancies of the periocular region were primarily treated surgically with few other options. As the genetic bases of these tumors have become elucidated, targeted therapies aimed specifically at pathways that are felt to be responsible for cellular proliferation and uncontrolled growth have emerged with new promise. This review contains a summary of the various genetic implications of cutaneous neoplasms as well as their corresponding targeted systemic therapies.},
	keywords = {Eyelid Neoplasms, Humans, Molecular Biology, Molecular Targeted Therapy, Skin Neoplasms},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825278},
	author = {Lee, Nahyoung Grace and Kim, Leo A and Freitag, Suzanne K}
}
@article {882961,
	title = {Long-term Visual Outcomes and Complications of Boston Keratoprosthesis Type II Implantation.},
	journal = {Ophthalmology},
	volume = {124},
	number = {1},
	year = {2017},
	pages = {27-35},
	abstract = {PURPOSE: To report the long-term visual outcomes and complications after Boston keratoprosthesis type II implantation in the largest single-center case series with the longest average follow-up. DESIGN: Retrospective review of consecutive clinical case series. PARTICIPANTS: Between January 1992 and April 2015 at the Massachusetts Eye and Ear Infirmary, 48 eyes of 44 patients had keratoprosthesis type II implanted by 2 surgeons (C.H.D. and J.C.). METHODS: For each eye, data were collected and analyzed on the preoperative characteristics, intraoperative procedures, and postoperative course. MAIN OUTCOME MEASURES: Visual acuity outcomes, postoperative complications, and device retention. RESULTS: The most common indications for surgery were Stevens-Johnson syndrome in 41.7\% (20 of 48 eyes) and mucous membrane pemphigoid in 41.7\% (20 of 48 eyes). Mean follow-up duration was 70.2 months (standard deviation, 61.8 months; median, 52 months; range, 6 months to 19.8 years). Almost all patients (95.8\%, 46 of 48 eyes) had a preoperative visual acuity of 20/200 or worse. Postoperative visual acuity improved to 20/200 or better in 37.5\% (18 of 48 eyes) and to 20/100 or better in 33.3\% (16 of 48 eyes) at the last follow-up visit. The most common postoperative complication was retroprosthetic membrane formation in over half (60.4\%, 29 of 48 eyes). The most pressing postoperative complication was glaucoma onset or progression in about a third. Preexisting glaucoma was present in 72.9\% (35 of 48 eyes). Glaucoma progressed in 27.1\% (13 of 48 eyes) and was newly diagnosed in 8.3\% (4 of 48 eyes) after surgery. Other postoperative complications were tarsorrhaphy revision in 52.1\% (25 of 48 eyes), retinal detachment in 18.8\% (9 of 48 eyes), infectious endophthalmitis in 6.3\% (3 of 48 eyes), and choroidal detachment or hemorrhage in 8.3\% (4 of 48 eyes). Half of eyes retained their initial keratoprosthesis at the last follow-up (50.0\%, 24 of 48 eyes). CONCLUSIONS: The Boston keratoprosthesis type II is a viable option to salvage vision in patients with poor prognosis for other corneal procedures. Retroprosthetic membranes, keratoprosthesis retention, and glaucoma are major challenges in the postoperative period; however, the keratoprosthesis can still provide improved vision in a select group of patients.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.07.011},
	author = {Lee, Ramon and Khoueir, Ziad and Tsikata, Edem and Chodosh, James and Dohlman, Claes H and Chen, Teresa C}
}
@article {439621,
	title = {Involvement of corneal lymphangiogenesis in a mouse model of allergic eye disease.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {5},
	year = {2015},
	month = {2015 May 1},
	pages = {3140-8},
	abstract = {PURPOSE: The contribution of lymphangiogenesis (LA) to allergy has received considerable attention and therapeutic inhibition of this process via targeting VEGF has been considered. Likewise, certain inflammatory settings affecting the ocular mucosa can trigger pathogenic LA in the naturally avascular cornea. Chronic inflammation in allergic eye disease (AED) impacts the conjunctiva and cornea, leading to sight threatening conditions. However, whether corneal LA is involved is completely unknown. We addressed this using a validated mouse model of AED. METHODS: Allergic eye disease was induced by ovalbumin (OVA) immunization and chronic OVA exposure. Confocal microscopy of LYVE-1-stained cornea allowed evaluation of corneal LA, and qRT-PCR was used to evaluate expression of VEGF-C, -D, and -R3 in these mice. Administration of VEGF receptor (R) inhibitor was incorporated to inhibit corneal LA in AED. Immune responses were evaluated by in vitro OVA recall responses of T cells, and IgE levels in the serum. RESULTS: Confocal microscopy of LYVE-1-stained cornea revealed the distinct presence of corneal LA in AED, and corroborated by increased corneal expression of VEGF-C, -D, and -R3. Importantly, prevention of corneal LA in AED via VEGFR inhibition was associated with decreased T helper two responses and IgE production. Furthermore, VEGFR inhibition led a significant reduction in clinical signs of AED. CONCLUSIONS: Collectively, these data reveal that there is a distinct involvement of corneal LA in AED. Furthermore, VEGFR inhibition prevents corneal LA and consequent immune responses in AED.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-16186},
	author = {Lee, Hyun-Soo and Hos, Deniz and Blanco, Tomas and Bock, Felix and Reyes, Nancy J and Mathew, Rose and Cursiefen, Claus and Dana, Reza and Saban, Daniel R}
}
@article {1351160,
	title = {A novel pro-angiogenic function for interferon-γ-secreting natural killer cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {5},
	year = {2014},
	month = {2014 May 02},
	pages = {2885-92},
	abstract = {PURPOSE: To explore the function of natural killer (NK) cells in inflammatory angiogenesis in mice. METHODS: To study ocular angiogenic responses we used the cornea BFGF micropellet and the laser-induced choroidal neovascularization (CNV) mouse models (C57BL/6). To deplete NK cells in these models, we injected an anti-NK1.1 antibody or an isotype antibody as a control. Corneas or choroids were immunohistochemically stained for blood vessels (CD31), macrophages (F4/80), or CNV (isolectin-IB4). Vascular endothelial growth factors (VEGF), IFN-γ, or TNF-α levels were measured by real-time quantitative PCR (qPCR) or flow cytometry. A coculture assay of macrophages, NK cells, and human umbilical vein endothelial cells (HUVECs) was analyzed morphometrically to examine the ability of NK cells to induce angiogenesis in vitro. RESULTS: Our data demonstrate that in vivo depletion of NK cells leads to a significant reduction of corneal angiogenesis and CNV. Furthermore, NK cell depletion reduces macrophage infiltration into the cornea and mRNA expression levels of VEGF-A, VEGF-C, and VEGFR3 at day 7 after micropellet insertion. In the laser-induced CNV model, our data show that NK cell depletion leads to decreased areas of CNV and significantly reduced mRNA expression of VEGFs and IFN-γ in the choroid. An in vitro coculture assay shows an IFN-γ-dependent increase in VEGF expression levels, thereby increasing endothelial cell proliferation. CONCLUSIONS: Our findings demonstrate a novel pro-angiogenic function for NK cells, indicating that IFN-γ-secreting NK cells can induce angiogenesis by promoting enhanced VEGF expression by macrophages.},
	keywords = {Animals, Choroidal Neovascularization, Cornea, Disease Models, Animal, Immunohistochemistry, Interferon-gamma, Killer Cells, Natural, Macrophages, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, RNA, Messenger, Vascular Endothelial Growth Factors},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14093},
	author = {Lee, Hyun Soo and Schlereth, Simona L and Park, Eun Y and Emami-Naeini, Parisa and Chauhan, Sunil K and Dana, Reza}
}
@article {1109841,
	title = {Nonmediated, Label-Free Based Detection of Cardiovascular Biomarker in a Biological Sample},
	journal = {Adv Healthc Mater},
	volume = {6},
	number = {17},
	year = {2017},
	month = {2017 Sep},
	abstract = {Direct electrochemical (EC) monitoring in a cell culture medium without electron transporter as called mediator is attractive topic in vitro organoid based on chip with frequently and long-time monitoring since it can avoid to its disadvantage as stability, toxicity. Here, direct monitoring with nonmediator is demonstrated based on impedance spectroscopy under the culture medium in order to overcome the limitation of mediator. The applicability of EC monitoring is shown by detecting alpha-1-anti trypsin (A1AT) which is known as biomarkers for cardiac damage and is widely chosen in organoid cardiac cell-based chip. The validity of presented EC monitoring is proved by observing signal processing and transduction in medium, mediator, medium-mediator complex. After the observation of electron behavior, A1AT as target analyte is immobilized on the electrode and detected using antibody-antigen interaction. As a result, the result indicates limit of detection is 10 ng mL(-1) and linearity for the 10-1000 ng mL(-1) range, with a sensitivity of 3980 nF (log [g mL])(-1) retaining specificity. This EC monitoring is based on label-free and reagentless detection, will pave the way to use for continuous and simple monitoring of in vitro organoid platform.},
	issn = {2192-2659},
	doi = {10.1002/adhm.201700231},
	author = {Lee, JuKyung and Shin, SuRyon and Desalvo, Anna and Lee, Geonhui and Lee, Jeong Yoon and Polini, Alessandro and Chae, Sukyoung and Jeong, Hobin and Kim, Jonghan and Choi, Haksoo and Lee, HeaYeon}
}
@article {1318868,
	title = {Simultaneous ipsilateral transconjunctival repair of upper and lower eyelid retraction in thyroid-associated ophthalmopathy},
	journal = {Orbit},
	year = {2018},
	month = {2018 May 09},
	pages = {1-6},
	abstract = {PURPOSE: To report a simple, highly effective technique of simultaneous transconjunctival repair of upper and lower eyelid retraction in patients with thyroid eye disease (TED). METHODS: A retrospective interventional case review was conducted on 22 eyes of 19 TED patients. The lower eyelid was recessed with placement of a tarsoconjunctival spacer graft harvested from the upper eyelid. The upper eyelid was then recessed through the conjunctival incision used to harvest the tarsal graft. A temporary tarsorrhaphy was placed for 5-7\&nbsp;days. The postoperative outcome was assessed by measuring the margin reflex distance of the upper eyelid (MRD1), inferior scleral show (ISS), and lagophthalmos. RESULTS: The absolute change in MRD1 ranged from 0 to 5\&nbsp;mm with an average of 1.86 {\textpm} 1.34\&nbsp;mm. The absolute change in ISS ranged from 0 to 2\&nbsp;mm with an average of 1.3 {\textpm} 0.49\&nbsp;mm. One patient had postoperative lagophthalmos and 17 of 19 had improvement in their ocular surface exposure symptoms. None of the patients{\textquoteright} grafts were observed to undergo absorption during the postoperative course. CONCLUSIONS: This technique of harvesting a free tarsoconjunctival graft from the upper eyelid as a posterior spacer for the lower while simultaneously recessing the upper eyelid through the same incision is an effective and durable method of correcting eyelid retraction in TED.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2018.1474237},
	author = {Lee, Nahyoung Grace and Habib, Larissa and Hall, Jonathan and Freitag, Suzanne K}
}
@article {1483613,
	title = {Lysosome-associated membrane protein-2 deficiency increases the risk of reactive oxygen species-induced ferroptosis in retinal pigment epithelial cells},
	journal = {Biochem Biophys Res Commun},
	volume = {521},
	number = {2},
	year = {2020},
	month = {2020 Jan 08},
	pages = {414-419},
	abstract = {Lysosome-associated membrane protein-2 (LAMP2), is a highly glycosylated lysosomal membrane protein involved in chaperone mediated autophagy. Mutations of LAMP2 cause the classic triad of myopathy, cardiomyopathy and encephalopathy of Danon disease (DD). Additionally, retinopathy has also been observed in young DD patients, leading to vision loss. Emerging evidence show LAMP2-deficiency to be involved in oxidative stress (ROS) but the mechanism remains obscure. In the present study, we found that tert-butyl hydroperoxide or antimycin A induced more cell death in LAMP2 knockdown (LAMP2-KD) than in control ARPE-19 cells. Mechanistically, LAMP2-KD reduced the concentration of cytosolic cysteine, resulting in low glutathione (GSH), inferior antioxidant capability and mitochondrial lipid peroxidation. ROS induced RPE cell death through ferroptosis. Inhibition of glutathione peroxidase 4 (GPx4) increased lethality in LAMP2-KD cells compared to controls. Cysteine and glutamine supplementation restored GSH and prevented ROS-induced cell death of LAMP2-KD RPE cells.},
	issn = {1090-2104},
	doi = {10.1016/j.bbrc.2019.10.138},
	author = {Lee, Jong-Jer and Ishihara, Kenji and Notomi, Shoji and Efstathiou, Nikolaos E and Ueta, Takashi and Maidana, Daniel and Chen, XiaoHong and Iesato, Yasuhiro and Caligiana, Alberto and Vavvas, Demetrios G}
}
@article {1417565,
	title = {Impact of dynamin 2 on adenovirus nuclear entry},
	journal = {Virology},
	volume = {529},
	year = {2019},
	month = {2019 Mar},
	pages = {43-56},
	abstract = {The large GTPase dynamin 2 controls both endosomal fission and microtubule acetylation. Here we report that dynamin 2 alters microtubules and regulates the trafficking of human adenovirus type 37. Dynamin 2 knockdown by siRNA in infected cells resulted in accumulation of acetylated tubulin, repositioning of microtubule organizing centers (MTOCs) closer to cell nuclei, increased virus in the cytosol (with a compensatory decrease in endosomal virus), reduced proinflammatory cytokine induction, and increased binding of virus to the nucleoporin, Nup358. These events led to increased viral DNA nuclear entry and viral replication. Overexpression of dynamin 2 generated opposite effects. Therefore, dynamin 2 inhibits adenovirus replication and promotes innate immune responses by the infected cell. MTOC transposition in dynamin 2 knockdown promotes a closer association with nuclear pore complexes to facilitate viral DNA delivery. Dynamin 2 plays a key role in adenoviral trafficking and influences host responses to infection.},
	issn = {1096-0341},
	doi = {10.1016/j.virol.2019.01.008},
	author = {Lee, Ji Sun and Ismail, Ashrafali M and Lee, Jeong Yoon and Zhou, Xiaohong and Materne, Emma C and Chodosh, James and Rajaiya, Jaya}
}
@article {1363138,
	title = {A review of the clinical and genetic aspects of aniridia},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {306-12},
	abstract = {Aniridia classically presents with a bilateral congenital absence or malformation of the irides, foveal hypoplasia, and nystagmus, and patients tend to develop visually significant pre-senile cataracts and keratopathy. Additionally, they are at high risk for developing glaucoma. Classic aniridia can be genetically defined as the presence of a PAX6 gene deletion or loss-of-function mutation that results in haploinsufficiency. Variants of aniridia, which include a condition previously referred to as autosomal dominant keratitis, are likely due to PAX6 mutations that lead to partial loss of PAX6 function. Aniridia-associated keratopathy (AAK) is a progressive and potentially debilitating problem affecting aniridic patients. The current treatments for AAK are to replace the limbal stem cells through keratolimbal allograft (KLAL) with or without subsequent keratoplasty for visual rehabilitation, or to implant a Boston type 1 keratoprosthesis. Future therapies for AAK may be aimed at the genetic modification of corneal limbal stem cells.},
	keywords = {Aniridia, Corneal Diseases, Eye Proteins, Gene Deletion, Homeodomain Proteins, Humans, Mutation, Paired Box Transcription Factors, PAX6 Transcription Factor, Repressor Proteins},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825293},
	author = {Lee, Hyunjoo J and Colby, Kathryn A}
}
@article {1460380,
	title = {Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes},
	journal = {Ophthalmol Retina},
	volume = {3},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {694-702},
	abstract = {PURPOSE: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. DESIGN: Multicenter, interventional, retrospective case-control study. PARTICIPANTS: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up. METHODS: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery. MAIN OUTCOME MEASURES: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months. RESULTS: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5\%) showed MHEP. Patients with FTMH and MHEP were older (P \&lt; 0.002) and more often men (P\&nbsp;= 0.001), and showed more advanced macular hole stages than those without MHEP (P\&nbsp;= 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P \&lt; 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P\&nbsp;= 0.019) with higher rates of ellipsoid and external limiting membrane defects (P \&lt; 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7\% vs. 4.8\%; P\&nbsp;= 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P \&lt; 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P\&nbsp;= 0.031) and for single-surgery nonclosure (P\&nbsp;= 0.009) and that ILM peeling improved single-surgery closure rates (P\&nbsp;= 0.026). CONCLUSIONS: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery.},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.03.022},
	author = {Lee Kim, Esther and Weiner, Adam J and Ung, Cindy and Roh, Miin and Wang, Jay and Lee, Ivan J and Huang, Natalie T and Stem, Maxwell and Dahrouj, Mohammad and Eliott, Dean and Vavvas, Demetrios G and Young, Lucy H Y and Williams, George A and Garretson, Bruce R and Kim, Ivana K and Hassan, Tarek S and Mukai, Shizuo and Ruby, Alan J and Faia, Lisa J and Capone, Antonio and Comander, Jason and Kim, Leo A and Wu, David M and Drenser, Kimberly A and Woodward, Maria A and Wolfe, Jeremy D and Yonekawa, Yoshihiro}
}
@article {1402582,
	title = {Case 39-2018: An 18-Year-Old Man with Diplopia and Proptosis of the Left Eye},
	journal = {N Engl J Med},
	volume = {379},
	number = {25},
	year = {2018},
	month = {2018 Dec 20},
	pages = {2452-2461},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc1807503},
	author = {Lefebvre, Daniel R and Reinshagen, Katherine L and Yoon, Michael K and Stone, John H and Stagner, Anna M}
}
@article {541356,
	title = {A Case Series and Review of Bisphosphonate-associated Orbital Inflammation},
	journal = {Ocul Immunol Inflamm},
	volume = {24},
	number = {2},
	year = {2016},
	month = {2016},
	pages = {134-9},
	abstract = {PURPOSE: To report the largest series of new cases to date of bisphosphate-associated orbital inflammation.

METHODS: A retrospective case review of patients with orbital inflammation following treatment with systemic bisphosphonate.

RESULTS: Six patients over an 18-month period (2 males, 4 females) with an average age of 62.2 years had onset of orbital inflammatory symptoms 1-11 days after intravenous bisphosphonate infusion or, in 1 case, 4 weeks after initiation of oral bisphosphonate therapy. Imaging revealed diffuse orbital involvement in 3 cases, isolated lateral rectus muscle involvement in 2 cases, and superior rectus-levator involvement in 1 case. Two patients{\textquoteright} symptoms resolved spontaneously within 2 weeks, and 3 responded rapidly and completely to corticosteroid therapy. The 1 patient on oral bisphosphonate had a slower but complete response to corticosteroid treatment.

CONCLUSION: Clinicians should be aware of the association between acute orbital inflammation and recent treatment with systemic bisphosphonate medication.},
	keywords = {Aged, Alendronate, Bone Density Conservation Agents, Diphosphonates, Female, Humans, Imidazoles, Magnetic Resonance Imaging, Male, Middle Aged, Orbital Cellulitis, Orbital Pseudotumor, Remission, Spontaneous, Retrospective Studies},
	issn = {1744-5078},
	doi = {10.3109/09273948.2014.942747},
	author = {Lefebvre, Daniel R and Mandeville, John T and Yonekawa, Yoshihiro and Arroyo, Jorge G and Torun, Nurhan and Freitag, Suzanne K}
}
@article {382601,
	title = {CT-Based Measurements of the Sphenoid Trigone in Different Sex and Race.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {2},
	year = {2015},
	month = {2015 Mar-Apr},
	pages = {155-8},
	abstract = {PURPOSE: In thyroid orbitopathy, surgical treatment of exophthalmos and compressive optic neuropathy is orbital decompression. Deep lateral wall decompression has been advocated alone or combined with the medial wall for a "balanced" decompression. The degree of lateral decompression is dependent on the volume of the sphenoid trigone comprising the deep lateral orbital wall. This study aims to compare the volume of the trigone in various races in men and women. METHODS: After Institutional Review Board approval, patients with normal sinus CT scans (Siemens Somatom 40-slice) were retrospectively reviewed. Inclusion criteria were men and women aged 30 to 60 years, no orbital disease or surgery, normal orbital CT scans, and self-reported race (Asian, black/African American, white). Scans were measured with imaging software (Synapse, Fujifilm USA). The superior and inferior extents of the measured trigone were the superior and inferior orbital fissures, respectively. In the axial CT plane, the areas of each slice of the right and left trigone were manually outlined with the software and volume subsequently calculated based on the slice thickness (2 mm). Comparisons between groups were made via repeated measures analysis of variance. RESULTS: One hundred twenty subjects were included, 20 from each subgroup, yielding 240 measured orbits. The overall volume of the sphenoid trigone for all groups combined was 1.53 cm (standard deviation 0.72 cm). Mean male volume was significantly larger than mean female volume (1.71 {\textpm} 0.83 cm vs. 1.35 {\textpm} 0.55 cm; p = 0.004). Average left side volume was larger than paired right side volume (1.58 {\textpm} 0.74 cm vs. 1.49 {\textpm} 0.71 cm; p = 0.02). There were no significant differences in average volumes between races (p = 0.17). CONCLUSIONS: The mean sphenoid trigone volume was larger in men than in women. There were no significant differences in volume between racial groups. The data showed significant interindividual and intraindividual variability. When analyzing these data for the purposes of orbital decompression, planning should be based on each side of each patient, as the expected degree of lateral decompression may vary greatly.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000370},
	author = {Lefebvre, Daniel R and Yoon, Michael K}
}
@article {313261,
	title = {Cellular neurothekeoma of the eyelid: a unique internal palpebral presentation},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {30},
	number = {4},
	year = {2014},
	month = {2014 Jul-Aug},
	pages = {e91-2},
	abstract = {A 50-year-old woman presented with a mass lesion of the inferolateral palpebral conjunctiva similar in appearance to a chalazion, but unusual enough in presentation that excisional biopsy was initially performed. Histopathologic analysis revealed a dermal fibrohistiocytic neoplasm consistent with cellular neurothekeoma. Neurothekeoma is a benign tumor; the cellular variant is rare and of unclear histogenesis. Completely internal eyelid location is particularly rare, with other identifiable case reports of cellular neurothekeoma palpebrae referring to external or unspecified eyelid location. This case provides an example of the chalazion as masquerader and re-emphasizes the importance of maintaining a broad differential diagnosis and high index of suspicion regarding atypically appearing chalazia.},
	keywords = {Biomarkers, Tumor, Biopsy, Conjunctiva, Diagnosis, Differential, Eyelid Neoplasms, Female, Humans, Middle Aged, Neurothekeoma, Skin Neoplasms},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e3182a22aea},
	author = {Lefebvre, Daniel R and Robinson-Bostom, Leslie and Migliori, Michael E}
}
@article {1364505,
	title = {Update on imaging of the lacrimal drainage system},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {175-86},
	abstract = {Epiphora is a common problem seen by the ophthalmologist. There are numerous etiologies of a watering eye, and the underlying diagnosis is not always clear. A variety of in-office examination techniques and procedures exist to aid with diagnosis and determination of appropriate therapy, but sometimes the diagnosis remains elusive, or an instituted therapy fails. Lacrimal imaging, particularly in these cases, can be helpful in assessing the function and anatomy of the lacrimal drainage system. This review serves to examine the literature of the last 10 years concerning imaging of the lacrimal drainage system.},
	keywords = {Dacryocystorhinostomy, Humans, Lacrimal Duct Obstruction, Nasolacrimal Duct, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.711413},
	author = {Lefebvre, Daniel R and Freitag, Suzanne K}
}
@article {1573113,
	title = {Differentiating Moebius syndrome and other congenital facial weakness disorders with electrodiagnostic studies},
	journal = {Muscle Nerve},
	volume = {63},
	number = {4},
	year = {2021},
	month = {2021 04},
	pages = {516-524},
	abstract = {INTRODUCTION: Congenital facial weakness (CFW) can result from facial nerve paresis with or without other cranial nerve and systemic involvement, or generalized neuropathic and myopathic disorders. Moebius syndrome is one type of CFW. In this study we explored the utility of electrodiagnostic studies (EDx) in the evaluation of individuals with CFW. METHODS: Forty-three subjects enrolled prospectively into a dedicated clinical protocol and had EDx evaluations, including blink reflex and facial and peripheral nerve conduction studies, with optional needle electromyography. RESULTS: MBS and hereditary congenital facial paresis (HCFP) subjects had low-amplitude cranial nerve 7 responses without other neuropathic or myopathic findings. Carriers of specific pathogenic variants in TUBB3 had, in addition, a generalized sensorimotor axonal polyneuropathy with demyelinating features. Myopathic findings were detected in individuals with Carey-Fineman-Ziter syndrome, myotonic dystrophy, other undefined myopathies, or CFW with arthrogryposis, ophthalmoplegia, and other system involvement. DISCUSSION: EDx in CFW subjects can assist in characterizing the underlying pathogenesis, as well as guide diagnosis and genetic counseling.},
	keywords = {Adult, Diagnosis, Differential, Facial Paralysis, Female, Heterozygote, Humans, Male, Mobius Syndrome, Muscular Diseases, Mutation, Pierre Robin Syndrome},
	issn = {1097-4598},
	doi = {10.1002/mus.27159},
	author = {Lehky, Tanya and Joseph, Reversa and Toro, Camilo and Wu, Tianxia and Van Ryzin, Carol and Gropman, Andrea and Facio, Flavia M and Webb, Bryn D and Jabs, Ethylin W and Barry, Brenda S and Engle, Elizabeth C and Collins, Francis S and Manoli, Irini and Moebius Syndrome Research Consortium}
}
@article {382411,
	title = {RasGAP Promotes Autophagy and Thereby Suppresses Platelet-Derived Growth Factor Receptor-Mediated Signaling Events, Cellular Responses, and Pathology.},
	journal = {Mol Cell Biol},
	volume = {35},
	number = {10},
	year = {2015},
	month = {2015 May 15},
	pages = {1673-85},
	abstract = {Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) make profound contributions to both physiology and pathology. While it is widely believed that direct (PDGF-mediated) activation is the primary mode of activating PDGFRs, the discovery that they can also be activated indirectly begs the question of the relevance of the indirect mode of activating PDGFRs. In the context of a blinding eye disease, indirect activation of PDGFRα results in persistent signaling, which suppresses the level of p53 and thereby promotes viability of cells that drive pathogenesis. Under the same conditions, PDGFRβ fails to undergo indirect activation. In this paper, we report that RasGAP (GTPase-activating protein of Ras) prevented indirect activation of PDGFRβ. RasGAP, which associates with PDGFRβ but not PDGFRα, reduced the level of mitochondrion-derived reactive oxygen species, which are required for enduring activation of PDGFRs. Furthermore, preventing PDGFRβ from associating with RasGAP allowed it to signal enduringly and drive pathogenesis of a blinding eye disease. These results indicate a previously unappreciated role of RasGAP in antagonizing indirect activation of PDGFRβ, define the underlying mechanism, and raise the possibility that PDGFRβ-mediated diseases involve indirect activation of PDGFRβ.},
	issn = {1098-5549},
	doi = {10.1128/MCB.01248-14},
	author = {Lei, Hetian and Qian, Cynthia X and Lei, Jinghu and Haddock, Luis J and Mukai, Shizuo and Kazlauskas, Andrius}
}
@article {1351161,
	title = {A reactive oxygen species-mediated, self-perpetuating loop persistently activates platelet-derived growth factor receptor α},
	journal = {Mol Cell Biol},
	volume = {34},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {110-22},
	abstract = {The platelet-derived growth factor (PDGF) receptors (PDGFRs) are central to a spectrum of human diseases. When PDGFRs are activated by PDGF, reactive oxygen species (ROS) and Src family kinases (SFKs) act downstream of PDGFRs to enhance PDGF-mediated tyrosine phosphorylation of various signaling intermediates. In contrast to these firmly established principles of signal transduction, much less is known regarding the recently appreciated ability of ROS and SFKs to indirectly and chronically activate monomeric PDGF receptor α (PDGFRα) in the setting of a blinding condition called proliferative vitreoretinopathy (PVR). In this context, we made a series of discoveries that substantially expands our appreciation of epigenetic-based mechanisms to chronically activate PDGFRα. Vitreous, which contains growth factors outside the PDGF family but little or no PDGFs, promoted formation of a unique SFK-PDGFRα complex that was dependent on SFK-mediated phosphorylation of PDGFRα and activated the receptor{\textquoteright}s kinase activity. While vitreous engaged a total of five receptor tyrosine kinases, PDGFRα was the only one that was activated persistently (at least 16 h). Prolonged activation of PDGFRα involved mTOR-mediated inhibition of autophagy and accumulation of mitochondrial ROS. These findings reveal that growth factor-containing biological fluids, such as vitreous, are able to tirelessly activate PDGFRα by engaging a ROS-mediated, self-perpetuating loop. },
	keywords = {Animals, Autophagy, Blotting, Western, Cell Line, Cells, Cultured, Humans, Intercellular Signaling Peptides and Proteins, Microscopy, Confocal, Mitochondria, Mutation, Phosphorylation, Protein Binding, Rabbits, Reactive Oxygen Species, Receptor, Platelet-Derived Growth Factor alpha, Signal Transduction, src-Family Kinases, Time Factors, TOR Serine-Threonine Kinases, Vitreous Body},
	issn = {1098-5549},
	doi = {10.1128/MCB.00839-13},
	author = {Lei, Hetian and Kazlauskas, Andrius}
}
@article {1573126,
	title = {Reply to Green and Hume: Nonmicroglia peripheral immune effects of short-term CSF1R inhibition with PLX5622},
	journal = {Proc Natl Acad Sci U S A},
	volume = {118},
	number = {4},
	year = {2021},
	month = {2021 Jan 26},
	issn = {1091-6490},
	doi = {10.1073/pnas.2020660118},
	author = {Lei, Fengyang and Cui, Naiwen and Zhou, Chengxin and Chodosh, James and Vavvas, Demetrios G and Paschalis, Eleftherios I}
}
@article {1363141,
	title = {Detection of H2O2-mediated phosphorylation of kinase-inactive PDGFRα},
	journal = {Methods Enzymol},
	volume = {528},
	year = {2013},
	month = {2013},
	pages = {189-94},
	abstract = {Platelet-derived growth factor (PDGF) receptor α (PDGFRα) belongs to the 58-member family of receptor tyrosine kinases and contributes to a variety of physiological and pathological settings. Activation of PDGFRα proceeds by at least two mechanisms. The traditional route involves PDGF-dependent dimerization and activation of the receptor{\textquoteright}s intrinsic kinase activity. The second mechanism proceeds intracellularly and involves reactive oxygen species and Src family kinases, which activate monomeric PDGFRα. Herein we describe an assay to investigate reactive oxygen species-mediated phosphorylation of PDGFRα that is independent of the receptor{\textquoteright}s intrinsic kinase activity.},
	keywords = {Cell Line, Gene Expression Regulation, Humans, Hydrogen Peroxide, Immunoprecipitation, Mutation, Phosphorylation, Platelet-Derived Growth Factor, Reactive Oxygen Species, Receptor, Platelet-Derived Growth Factor alpha, Signal Transduction, Transfection},
	issn = {1557-7988},
	doi = {10.1016/B978-0-12-405881-1.00011-2},
	author = {Lei, Hetian and Kazlauskas, Andrius}
}
@article {1532362,
	title = {CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	number = {38},
	year = {2020},
	month = {2020 Sep 22},
	pages = {23336-23338},
	abstract = {Colony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a method for microglia depletion, with the assumption that it does not affect peripheral immune cells. Here, we show that CSF1R inhibition by PLX5622 indeed affects the myeloid and lymphoid compartments, causes long-term changes in bone marrow-derived macrophages by suppressing interleukin 1β, CD68, and phagocytosis but not CD208, following exposure to endotoxin, and also reduces the population of resident and interstitial macrophages of peritoneum, lung, and liver but not spleen. Thus, small-molecule CSF1R inhibition is not restricted to microglia, causing strong effects on circulating and tissue macrophages that perdure long after cessation of the treatment. Given that peripheral monocytes repopulate the central nervous system after CSF1R inhibition, these changes have practical implications for relevant experimental data.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1922788117},
	author = {Lei, Fengyang and Cui, Naiwen and Zhou, Chengxin and Chodosh, James and Vavvas, Demetrios G and Paschalis, Eleftherios I}
}
@article {303991,
	title = {Intraocular pressure fluctuation and glaucoma progression: what do we know?},
	journal = {Br J Ophthalmol},
	volume = {98},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {1315-1319},
	abstract = {While mean intraocular pressure (IOP) has long been known to correlate with glaucomatous damage, the role of IOP fluctuation is less clearly defined. There is extensive evidence in the literature for and against the value of short-term and long-term IOP fluctuation in the evaluation and prognosis of patients with glaucoma. We present here the arguments made by both sides, as well as a discussion of the pitfalls of prior research and potential directions for future studies. Until a reliable method is developed that allows for constant IOP monitoring, many variables will continue to hinder us from drawing adequate conclusions regarding the significance of IOP variation.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2013-303980},
	author = {Leidl, Matthew C and Choi, Catherine J and Syed, Zeba A and Melki, Samir A}
}
@article {1661590,
	title = {Editorial: Regulation of inflammation and metabolism in retinal neurodegenerative disorders},
	journal = {Front Neurosci},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {1102385},
	issn = {1662-4548},
	doi = {10.3389/fnins.2022.1102385},
	author = {Leinonen, Henri and Zhou, Tianwei Ellen and Ballios, Brian G and Kauppinen, Anu and Fu, Zhongjie}
}
@article {1688226,
	title = {Neural and M{\"u}ller glial adaptation of the retina to photoreceptor degeneration},
	journal = {Neural Regen Res},
	volume = {18},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {701-707},
	abstract = {The majority of inherited retinal degenerative diseases and dry age-related macular degeneration are characterized by decay of the outer retina and photoreceptors, which leads to progressive loss of vision. The inner retina, including second- and third-order retinal neurons, also shows aberrant structural changes at all stages of degeneration. M{\"u}ller glia, the major glial cells maintain retinal homeostasis, activating and rearranging immediately in response to photoreceptor stress. These phenomena are collectively known as retinal remodeling and are anatomically well described, but their impact on visual function is less well characterized. Retinal remodeling has traditionally been considered a detrimental chain of events that decreases visual function. However, emerging evidence from functional assays suggests that remodeling could also be a part of a survival mechanism wherein the inner retina responds plastically to outer retinal degeneration. The visual system{\textasciiacute}s first synapses between the photoreceptors and bipolar cells undergo rewiring and functionally compensate to maintain normal signal output to the brain. Distinct classes of retinal ganglion cells remain even after the massive loss of photoreceptors. M{\"u}ller glia possess the regenerative potential for retinal recovery and possibly exert adaptive transcriptional changes in response to neuronal loss. These types of homeostatic changes could potentially explain the well-maintained visual function observed in patients with inherited retinal degenerative diseases who display prominent anatomic retinal pathology. This review will focus on our current understanding of retinal neuronal and M{\"u}ller glial adaptation for the potential preservation of retinal activity during photoreceptor degeneration. Targeting retinal self-compensatory responses could help generate universal strategies to delay sensory disease progression.},
	issn = {1673-5374},
	doi = {10.4103/1673-5374.354511},
	author = {Leinonen, Henri O and Bull, Edward and Fu, Zhongjie}
}
@article {1580477,
	title = {Community-genotype methicillin-resistant Staphylococcus aureus skin and soft tissue infections in Latin America: a systematic review},
	journal = {Braz J Infect Dis},
	year = {2021},
	month = {2021 Feb 16},
	pages = {101539},
	abstract = {BACKGROUND: Community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) emerged in the 1990s as a global community pathogen primarily involved in skin and soft tissue infections (SSTIs) and pneumonia. To date, the CG-MRSA SSTI burden in Latin America (LA) has not been assessed. OBJECTIVE: The main objective of this study was to report the rate and genotypes of community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) causing community-onset skin and soft tissue infections (CO-SSTIs) in LA over the last two decades. In addition, this research determined relevant data related to SSTIs due to CG-MRSA, including risk factors, other invasive diseases, and mortality. DATA SOURCES: Relevant literature was searched and extracted from five major databases: Embase, PubMed, LILACS, SciELO, and Web of Science. METHODS: A systematic review was performed, and a narrative review was constructed. RESULTS: An analysis of 11 studies identified epidemiological data across LA, with Argentina presenting the highest percentage of SSTIs caused by CG-MRSA (88\%). Other countries had rates of CG-MRSA infection ranging from 0 to 51\%. Brazil had one of the lowest rates of CG-MRSA SSTI (4.5-25\%). In Argentina, being younger than 50 years of age and having purulent lesions were predictive factors for CG-MRSA CO-SSTIs. In addition, the predominant genetic lineages in LA belonged to sequence types 8, 30, and 5 (ST8, ST30, and ST5). CONCLUSION: There are significant regional differences in the rates of CG-MRSA causing CO-SSTIs. It is not possible to conclude whether or not CG-MRSA CO-SSTIs resulted in more severe SSTI presentations or in a higher mortality rate.},
	issn = {1678-4391},
	doi = {10.1016/j.bjid.2021.101539},
	author = {Leme, Rodrigo Cuiabano Paes and Martins Bispo, Paulo Jos{\'e} and Salles, Mauro Jos{\'e}}
}
@article {1773566,
	title = {Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease},
	journal = {medRxiv},
	year = {2023},
	month = {2023 Oct 05},
	abstract = {Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and with new innovative methods can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the GREGoR consortium. Each family{\textquoteright}s CNV data was analyzed using the seqr platform and candidate CNVs classified using the 2020 ACMG/ClinGen CNV interpretation standards. We developed additional evidence criteria to address situations not covered by the current standards. The addition of CNV calling to exome analysis identified causal CNVs for 173 families (2.6\%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb with estimates that 44\% would not have been detected by standard chromosomal microarrays. The causal CNVs consisted of 141 deletions, 15 duplications, 4 suspected complex structural variants (SVs), 3 insertions and 10 complex SVs, the latter two groups being identified by orthogonal validation methods. We interpreted 153 CNVs as likely pathogenic/pathogenic and 20 CNVs as high interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.},
	doi = {10.1101/2023.10.05.23296595},
	author = {Lemire, Gabrielle and Sanchis-Juan, Alba and Russell, Kathryn and Baxter, Samantha and Chao, Katherine R and Singer-Berk, Moriel and Groopman, Emily and Wong, Isaac and England, Eleina and Goodrich, Julia and Pais, Lynn and Austin-Tse, Christina and DiTroia, Stephanie and O{\textquoteright}Heir, Emily and Ganesh, Vijay S and Wojcik, Monica H and Evangelista, Emily and Snow, Hana and Osei-Owusu, Ikeoluwa and Fu, Jack and Singh, Mugdha and Mostovoy, Yulia and Huang, Steve and Garimella, Kiran and Kirkham, Samantha L and Neil, Jennifer E and Shao, Diane D and Walsh, Christopher A and Argili, Emanuela and Le, Carolyn and Sherr, Elliott H and Gleeson, Joseph and Shril, Shirlee and Schneider, Ronen and Hildebrandt, Friedhelm and Sankaran, Vijay G and Madden, Jill A and Genetti, Casie A and Beggs, Alan H and Agrawal, Pankaj B and Bujakowska, Kinga M and Place, Emily and Pierce, Eric A and Donkervoort, Sandra and B{\"o}nnemann, Carsten G and Gallacher, Lyndon and Stark, Zornitza and Tan, Tiong and White, Susan M and T{\"o}pf, Ana and Straub, Volker and Fleming, Mark D and Pollak, Martin R. and {\~O}unap, Katrin and Pajusalu, Sander and Donald, Kirsten A and Bruwer, Zandre and Ravenscroft, Gianina and Laing, Nigel G and MacArthur, Daniel G and Rehm, Heidi L and Talkowski, Michael E and Brand, Harrison and O{\textquoteright}Donnell-Luria, Anne}
}
@article {1598067,
	title = {Normobaric hyperoxia rapidly reduces diabetic macular oedema},
	journal = {Clin Exp Ophthalmol},
	year = {2021},
	month = {2021 Jun 15},
	issn = {1442-9071},
	doi = {10.1111/ceo.13961},
	author = {Lemire, Colin A and Seto, Brendan and Yamada, Keiko and Arroyo, Jorge G}
}
@article {1653594,
	title = {Direct modulation of microglial function by electrical field},
	journal = {Front Cell Dev Biol},
	volume = {10},
	year = {2022},
	month = {2022},
	pages = {980775},
	abstract = {Non-invasive electric stimulation (ES) employing a low-intensity electric current presents a potential therapeutic modality that can be applied for treating retinal and brain neurodegenerative disorders. As neurons are known to respond directly to ES, the effects of ES on glia cells are poorly studied. A key question is if ES directly mediates microglial function or modulates their activity merely via neuron-glial signaling. Here, we demonstrated the direct effects of ES on microglia in the BV-2 cells-an immortalized murine microglial cell line. The low current ES in a biphasic ramp waveform, but not that of rectangular or sine waveforms, significantly suppressed the motility and migration of BV-2 microglia in culture without causing cytotoxicity. This was associated with diminished cytoskeleton reorganization and microvilli formation in BV-2 cultures, as demonstrated by immunostaining of cytoskeletal proteins, F-actin and β-tubulin, and scanning electron microscopy. Moreover, ES of a ramp waveform reduced microglial phagocytosis of fluorescent zymosan particles and suppressed lipopolysaccharide (LPS)-induced pro-inflammatory cytokine expression in BV-2 cells as shown by Proteome Profiler Mouse Cytokine Array. The results of quantitative PCR and immunostaining for cyclooxygenase-2, Interleukin 6, and Tumor Necrosis Factor-α corroborated the direct suppression of LPS-induced microglial responses by a ramp ES. Transcriptome profiling further demonstrated that ramp ES effectively suppressed nearly half of the LPS-induced genes, primarily relating to cellular motility, energy metabolism, and calcium signaling. Our results reveal a direct modulatory effect of ES on previously thought electrically "non-responsive" microglia and suggest a new avenue of employing ES for anti-inflammatory therapy.},
	issn = {2296-634X},
	doi = {10.3389/fcell.2022.980775},
	author = {Lennikov, Anton and Yang, Menglu and Chang, Karen and Pan, Li and Saddala, Madhu Sudhana and Lee, Cherin and Ashok, Ajay and Cho, Kin-Sang and Utheim, Tor Paaske and Chen, Dong Feng}
}
@article {280901,
	title = {Idiopathic opticochiasmatic arachnoiditis.},
	journal = {J Neuroophthalmol},
	volume = {34},
	number = {3},
	year = {2014},
	month = {2014 Sep},
	pages = {251-4},
	abstract = {: A critical review of the literature indicates that idiopathic opticochiasmatic arachnoiditis, once considered an important consideration in patients with otherwise unexplained optic atrophy, is not a valid disease entity.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000089},
	author = {Lessell, Simmons and E Grzybowski, Andrzej}
}
@article {1573123,
	title = {Emotional recovery after ocular trauma: is there more than meets the eye?},
	journal = {Eye (Lond)},
	volume = {36},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {244-245},
	issn = {1476-5454},
	doi = {10.1038/s41433-020-01389-7},
	author = {Lester, Ethan G and Armstrong, Grayson W and Vranceanu, Ana-Maria}
}
@article {368996,
	title = {Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.},
	journal = {Ophthalmology},
	volume = {122},
	number = {5},
	year = {2015},
	month = {2015 May},
	pages = {939-48},
	abstract = {PURPOSE: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. DESIGN: Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. PARTICIPANTS: Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. METHODS: Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). MAIN OUTCOME MEASURES: Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. RESULTS: Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7\% and 61.5\% vs. 33.3\%, respectively) and remission rates (27.3\% and 38.5\% vs. 16.7\%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared safe and was well tolerated. CONCLUSIONS: Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.12.033},
	author = {Letko, Erik and Yeh, Steven and Foster, C Stephen and Pleyer, Uwe and Brigell, Mitchell and Grosskreutz, Cynthia L and AIN457A2208 Study Group}
}
@article {1351162,
	title = {Incidence of visual improvement in uveitis cases with visual impairment caused by macular edema},
	journal = {Ophthalmology},
	volume = {121},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {588-95.e1},
	abstract = {PURPOSE: Among cases of visually significant uveitic macular edema (ME), to estimate the incidence of visual improvement and identify predictive factors.

DESIGN: Retrospective cohort study.

PARTICIPANTS: Eyes with uveitis, seen at 5 academic ocular inflammation centers in the United States, for which ME was documented to be currently present and the principal cause of reduced visual acuity (,
	keywords = {Adult, Aged, Female, Fluorescein Angiography, HLA-B27 Antigen, Humans, Incidence, Macular Edema, Male, Middle Aged, Prognosis, Retrospective Studies, Tomography, Optical Coherence, Uveitis, Vision, Low, Visual Acuity, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2013.09.023},
	author = {Levin, Marc H and Pistilli, Maxwell and Daniel, Ebenezer and Gangaputra, Sapna S and Nussenblatt, Robert B and Rosenbaum, James T and Suhler, Eric B and Thorne, Jennifer E and Foster, C Stephen and Jabs, Douglas A and Levy-Clarke, Grace A and Kempen, John H}
}
@article {1125341,
	title = {Special Commentary: Early Clinical Development of Cell Replacement Therapy: Considerations for the National Eye Institute Audacious Goals Initiative},
	journal = {Ophthalmology},
	volume = {124},
	number = {7},
	year = {2017},
	month = {2017 Jul},
	pages = {926-934},
	abstract = {The National Eye Institute launched the Audacious Goals Initiative (AGI) in 2013 with the aim "to restore vision through the regeneration of neurons and neural connections in the eye and visual system." An AGI Town Hall held at the Association for Research in Vision and Ophthalmology Annual Meeting in 2016 brought together basic, translational, and clinical scientists to address the clinical implications of the AGI, with a particular emphasis on diseases amenable to regenerative medicine and strategies to deal with barriers to progess. An example of such a barrier is that replacement of lost neurons may be insufficient because damage to other neurons and non-neuronal cells is common in retinal and optic nerve disease. Reparative processes such as gliosis and fibrosis also can make it difficult to replenish and regenerate neurons. Other issues include choice of animal models, selecting appropriate endpoints, ethics of informed consent, and regulatory issues. Another area critical to next steps in the AGI is the choice of target diseases and the stage at which early development studies should be focused. For example, an advantage of doing clinical trials in patients with early disease is that supporting cellular and structural constituents are still likely to be present. However, regenerative studies in patients with late disease make it easier to detect the effects of replacement therapy against the background of severe visual loss, whereas it may be harder to detect incremental improvement in visual function in those with early disease and considerable remaining visual function. Achieving the goals of the AGI also requires preclinical advances, new imaging techniques, and optimizing translational issues. The work of the AGI is expected to take at least 10 years but should eventually result in therapies to restore some degree of vision to the blind.},
	keywords = {Animals, Cell- and Tissue-Based Therapy, Goals, Humans, National Eye Institute (U.S.), Ophthalmology, Optic Nerve Diseases, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.02.017},
	author = {Levin, Leonard A and Miller, Joan W and Zack, Donald J and Friedlander, Martin and Smith, Lois E H}
}
@article {1632288,
	title = {It is time for a moonshot to find "Cures" for diabetic retinal disease},
	journal = {Prog Retin Eye Res},
	volume = {90},
	year = {2022},
	month = {2022 Sep},
	pages = {101051},
	abstract = {Diabetic retinal disease (DRD), the most common complication of diabetes and a leading cause of blindness in working age individuals, is now understood to be a form of sensory neuropathy or neurovascular degeneration. Current treatments are focused on advanced vision-threatening disease and a single molecular target, vascular endothelial growth factor, has an approved therapy. We trace the evolution of understanding of DRD pathogenesis, identify new approaches to clinical assessment, trials infrastructure and design, and target identification to accelerate selection and evaluation of new therapeutics that will speed development of potentially curative interventions. Critically, the "Restoring Vision Moonshot" framework will address gaps in knowledge to be filled to achieve the goal of restoring sight and preventing vision loss in persons with diabetes.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Humans, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Vision Disorders},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2022.101051},
	author = {Levine, S Robert and Sapieha, Przemyslaw and Dutta, Sanjoy and Sun, Jennifer K and Gardner, Thomas W}
}
@article {1782426,
	title = {Report From the 2022 Mary Tyler Moore Vision Initiative Diabetic Retinal Disease Clinical Endpoints Workshop},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {11},
	year = {2023},
	month = {2023 Nov 01},
	pages = {33},
	abstract = {The Mary Tyler Moore Vision Initiative Diabetic Retinal Disease (DRD) Clinical Endpoints Workshop was held on October 22, 2022 to accelerate progress toward establishment of useful clinical and research endpoints and development of new therapeutics that have important relevance across the full spectrum of DRD pathology. More than 90 patient representatives, clinicians, scientists, funding and regulatory agencies, diagnostic, therapeutic and biotech industry representatives discussed the needs for new diagnostic and therapeutic approaches to prevent and restore retinal neurovascular unit integrity. Phase I of the MTM Vision Initiative plans, notably updating the DRD staging system and severity scale, establishing a human ocular biorepository and resource, and clinical endpoints and biomarker development and validation, was emphasized.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Humans, Retina},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.11.33},
	author = {Levine, S Robert and Myers, Martin G and Barunas, Ryan and Chang, Dolly S and Dutta, Sanjoy and Maddess, Ted and Liebmann, Jeffrey M and Sherman, Steve and Eydelman, Melvina and Sun, Jennifer K and Chambers, Wiley and Wickstr{\"o}m, Kerstin and Luhmann, Ulrich F O and Pallinat, Martin and Glassman, Adam and Aiello, Lloyd Paul and Markel, Dorene S and Gardner, Thomas W}
}
@article {1417566,
	title = {Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of Placental Insufficiency and with Systemic Inflammation},
	journal = {Am J Perinatol},
	volume = {36},
	number = {14},
	year = {2019},
	month = {2019 Dec},
	pages = {1442-1452},
	abstract = {OBJECTIVE:   To evaluate to what extent indicators of placenta insufficiency are associated with low concentrations of insulin-like growth factor 1 (IGF-1) and IGF-1-binding protein-1 (IGFBP-1) in neonatal blood, and to what extent the concentrations of these growth factors are associated with concentrations of proteins with inflammatory, neurotrophic, or angiogenic properties. STUDY DESIGN:   Using multiplex immunoassays, we measured the concentrations of IGF-1 and IGFBP-1, as well as 25 other proteins in blood spots collected weekly from >= 880 infants born before the 28th week of gestation, and sought correlates of concentrations in the top and bottom quartiles for gestational age and day the specimen was collected. RESULTS:   Medically indicated delivery and severe fetal growth restriction (sFGR) were associated with low concentrations of IGF-1 on the first postnatal day and with high concentrations of IGFBP-1 on almost all days. Elevated concentrations of IGF-1 and IGFBP-1 were accompanied by elevated concentrations of many other proteins with inflammatory, neurotrophic, or angiogenic properties. CONCLUSION:   Disorders associated with impaired placenta implantation and sFGR appear to account for a relative paucity of IGF-1 on the first postnatal day. Elevated concentrations of IGF-1 and especially IGFBP-1 were associated with same-day elevated concentrations of inflammatory, neurotrophic, and angiogenic proteins.},
	issn = {1098-8785},
	doi = {10.1055/s-0038-1677472},
	author = {Leviton, Alan and Allred, Elizabeth N and Fichorova, Raina N and VanderVeen, Deborah K and O{\textquoteright}Shea, T Michael and Kuban, Karl and Dammann, Olaf and ELGAN Study Investigators}
}
@article {1658658,
	title = {Case 36-2022: A 30-Year-Old Woman with Decreased Vision and Headache},
	journal = {N Engl J Med},
	volume = {387},
	number = {21},
	year = {2022},
	month = {2022 Nov 24},
	pages = {1980-1989},
	keywords = {Adult, Female, Headache, Humans, Vision Disorders},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc2211355},
	author = {Michael Levy and Chwalisz, Bart K and Kozak, Benjamin M and Yoon, Michael K and Shih, Helen A and Stagner, Anna M}
}
@article {1483602,
	title = {Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses},
	journal = {Nat Biomed Eng},
	volume = {4},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {97-110},
	abstract = {The success of base editors for the study and treatment of genetic diseases depends on the ability to deliver them in vivo to the relevant cell types. Delivery via adeno-associated viruses (AAVs) is limited by AAV packaging capacity, which precludes the use of full-length base editors. Here, we report the application of dual AAVs for the delivery of split cytosine and adenine base editors that are then reconstituted by trans-splicing inteins. Optimized dual AAVs enable in vivo base editing at therapeutically relevant efficiencies and dosages in the mouse brain (up to 59\% of unsorted cortical tissue), liver (38\%), retina (38\%), heart (20\%) and skeletal muscle (9\%). We also show that base editing corrects, in mouse brain tissue, a mutation that causes Niemann-Pick disease type C (a neurodegenerative ataxia), slowing down neurodegeneration and increasing lifespan. The optimized delivery vectors should facilitate the efficient introduction of targeted point mutations into multiple tissues of therapeutic interest.},
	issn = {2157-846X},
	doi = {10.1038/s41551-019-0501-5},
	author = {Levy, Jonathan M and Yeh, Wei-Hsi and Pendse, Nachiket and Davis, Jessie R and Hennessey, Erin and Butcher, Rossano and Koblan, Luke W and Comander, Jason and Liu, Qin and Liu, David R}
}
@article {1359936,
	title = {rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial},
	journal = {J Pediatr},
	volume = {206},
	year = {2019},
	month = {2019 Mar},
	pages = {56-65.e8},
	abstract = {OBJECTIVE: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 23 weeks to 27 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 {\textmu}g/kg/ 24 hours, continuous intravenous infusion from \&lt;24 hours of birth to postmenstrual age 29 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 40 weeks. Target exposure was >=70\% IGF-1 measurements within 28-109 {\textmu}g/L and >=70\% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53\% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3\% treated vs 44.9\% standard care), and an 89\% decrease in the evaluable set (4.8\% vs 44.9\%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1\% vs 23.3\%) and in the evaluable set (8.3\% vs 23.3\%). Fatal serious adverse events were reported in 19.7\% of treated infants (12/61) and 11.7\% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01096784.},
	issn = {1097-6833},
	doi = {10.1016/j.jpeds.2018.10.033},
	author = {Ley, David and Hallberg, Boubou and Hansen-Pupp, Ingrid and Dani, Carlo and Ramenghi, Luca A and Marlow, Neil and Beardsall, Kathryn and Bhatti, Faizah and Dunger, David and Higginson, Jason D and Mahaveer, Ajit and Mezu-Ndubuisi, Olachi J and Reynolds, Peter and Giannantonio, Carmen and van Weissenbruch, Mirjam and Barton, Norman and Tocoian, Adina and Hamdani, Mohamed and Jochim, Emily and Mangili, Alexandra and Chung, Jou-Ku and Turner, Mark A and Smith, Lois E H and Hellstr{\"o}m, Ann and study team}
}
@article {1302199,
	title = {Secretogranin III: a diabetic retinopathy-selective angiogenic factor},
	journal = {Cell Mol Life Sci},
	volume = {75},
	number = {4},
	year = {2018},
	month = {2018 Feb},
	pages = {635-647},
	abstract = {Secretogranin III (Scg3) is a member of the granin protein family that regulates the biogenesis of secretory granules. Scg3 was recently discovered as an angiogenic factor, expanding its functional role to extrinsic regulation. Unlike many other known angiogenic factors, the pro-angiogenic actions of Scg3 are restricted to pathological conditions. Among thousands of quantified endothelial ligands, Scg3 has the highest binding activity ratio to diabetic vs. healthy mouse retinas and lowest background binding to normal vessels. In contrast, vascular endothelial growth factor binds to and stimulates angiogenesis of both diabetic and control vasculature. Consistent with its role in pathological angiogenesis, Scg3-neutralizing antibodies alleviate retinal vascular leakage in mouse models of diabetic retinopathy and retinal neovascularization in oxygen-induced retinopathy mice. This review summarizes our current knowledge of Scg3 as a regulatory protein of secretory granules, highlights its new role as a highly disease-selective angiogenic factor, and envisions Scg3 inhibitors as "selective angiogenesis blockers" for targeted therapy.},
	issn = {1420-9071},
	doi = {10.1007/s00018-017-2635-5},
	author = {Li, Wei and Webster, Keith A and LeBlanc, Michelle E and Tian, Hong}
}
@article {1782241,
	title = {Bietti{\textquoteright}s crystalline dystrophy: genotyping and deep qualitative and quantitative phenotyping in preparation for clinical trials},
	journal = {Br J Ophthalmol},
	year = {2023},
	month = {2023 Nov 14},
	abstract = {PURPOSE: To qualitatively and quantitatively characterise the genotypes and phenotypes of Bietti{\textquoteright}s crystalline dystrophy (BCD) in a cohort of patients. DESIGN: Cross-sectional and observational study. METHODS: Clinically confirmed BCD patients were recruited for genotyping and phenotyping. Multiple retinal imaging modalities were employed. Atrophy in the fovea was adopted as major consideration for staging strategy, while percentage area of autofluorescence (AF) atrophy (PAFA) in the macula was determined for quantitation. RESULTS: In 74 clinically diagnosed BCD patients, c.802-8_810del17insGC was shown the predominant variant of the CYP4V2 gene (allele frequency 55.4\%). Sixty-two cases (123 eyes) with full imaging data were classified according to a modified criterion into stages 1 (n=8, 6.50\%), 2A (n=9, 7.32\%), 2B (n=17, 13.82\%), 3A (n=30, 24.39\%) and 3B (n=59, 47.97\%). The eyes of the stage 2B were particularly deemed {\textquoteright}high risk{\textquoteright} due to atrophy near fovea, while in stage 3A, though with remarkable foveal atrophy, preserved retinal pigment epithelium/photoreceptor islands near the fovea were found in 14 eyes. A tendency of increase in PAFA with age was found (rs=0.31, p=0.014). Significant PAFA increase was shown through stages 1 to 3B, and best-corrected visual acuity (BCVA, Logarithm of the Minimum Angle of Resolution) was shown to moderately correlate with PAFA (rs=0.56, p\&lt;0.001). CONCLUSION: The PAFA might be an efficient biomarker for BCD severities correlating with BCVA. The highly heterogeneous chorioretinopathy and BCVA of BCD cases appear to be associated with disease stages, progression types and patients{\textquoteright} ages. Foveal involvement should be of a major concern for consideration of potential therapeutic intervention.},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-322673},
	author = {Li, Qian and Wang, Cong and Zhang, Shengjuan and Fu, Zhongjie and Jiao, Xiaodong and Jin, Zi-Bing and Hejtmancik, James Fielding and Peng, Xiaoyan}
}
@article {1109846,
	title = {Identification of a Sj{\"o}gren{\textquoteright}s syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons},
	journal = {PLoS Genet},
	volume = {13},
	number = {6},
	year = {2017},
	month = {2017 Jun 22},
	pages = {e1006820},
	abstract = {Sj{\"o}gren{\textquoteright}s syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2{\textquoteright}-5{\textquoteright}-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 {\texttimes} 10-14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 {\texttimes} 10-9; odds ratio = 0.75; 95\% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3{\textquoteright} end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1006820},
	author = {He Li and Reksten, Tove Ragna and Ice, John A and Kelly, Jennifer A and Adrianto, Indra and Rasmussen, Astrid and Wang, Shaofeng and He, Bo and Grundahl, Kiely M and Glenn, Stuart B and Miceli-Richard, Corinne and Bowman, Simon and Lester, Sue and Eriksson, Per and Eloranta, Maija-Leena and Brun, Johan G and G{\o}ransson, Lasse G and Harboe, Erna and Guthridge, Joel M and Kaufman, Kenneth M and Kvarnstr{\"o}m, Marika and Cunninghame Graham, Deborah S and Patel, Ketan and Adler, Adam J and Farris, A Darise and Brennan, Michael T and Chodosh, James and Gopalakrishnan, Rajaram and Weisman, Michael H and Venuturupalli, Swamy and Wallace, Daniel J and Hefner, Kimberly S and Houston, Glen D and Huang, Andrew J W and Hughes, Pamela J and Lewis, David M and Radfar, Lida and Vista, Evan S and Edgar, Contessa E and Rohrer, Michael D and Stone, Donald U and Vyse, Timothy J and Harley, John B and Gaffney, Patrick M and James, Judith A and Turner, Sean and Alevizos, Ilias and Juan-Manuel Anaya and Rhodus, Nelson L and Segal, Barbara M and Montgomery, Courtney G and Scofield, R Hal and Kovats, Susan and Mariette, Xavier and R{\"o}nnblom, Lars and Witte, Torsten and Rischmueller, Maureen and Wahren-Herlenius, Marie and Omdal, Roald and Jonsson, Roland and Ng, Wan-Fai and for UK Primary Sj{\"o}gren{\textquoteright}s Syndrome Registry and Nordmark, Gunnel and Lessard, Christopher J and Sivils, Kathy L}
}
@article {1615211,
	title = {Association Between Diabetes, Diabetic Retinopathy, and Glaucoma},
	journal = {Curr Diab Rep},
	volume = {21},
	number = {10},
	year = {2021},
	month = {2021 Sep 08},
	pages = {38},
	abstract = {PURPOSE OF REVIEW: The strength of the relationship between diabetes, diabetic retinopathy (DR), and glaucoma remains controversial. We review evidence supporting and refuting this association and explore mechanistic pathological and treatment relationships linking these diseases. RECENT FINDINGS: While studies have shown diabetes/DR may increase the risk for glaucoma, this remains inconsistently demonstrated. Diabetes/DR may contribute toward glaucomatous optic neuropathy indirectly (either by increasing intraocular pressure or vasculopathy) or through direct damage to the optic nerve. However, certain elements of diabetes may slow glaucoma progression, and diabetic treatment may concurrently be beneficial in glaucoma management. Diabetes plays a significant role in poor outcomes after glaucoma surgery. While the relationship between diabetes/DR and glaucoma remains controversial, multiple mechanistic links connecting pathophysiology and management of diabetes, DR, and glaucoma have been made. However, a deeper understanding of the causes of disease association is needed.},
	issn = {1539-0829},
	doi = {10.1007/s11892-021-01404-5},
	author = {Li, Yangjiani and Mitchell, William and Tobias Elze and Zebardast, Nazlee}
}
@article {341706,
	title = {Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {12},
	year = {2014},
	month = {2014 Dec},
	pages = {8267-77},
	abstract = {PURPOSE: Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice. METHODS: Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA). RESULTS: TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation. CONCLUSIONS: Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15623},
	author = {Li, Jie and Liu, Chi-Hsiu and Sun, Ye and Gong, Yan and Fu, Zhongjie and Evans, Lucy P and Tian, Katherine T and Juan, Aimee M and Hurst, Christian G and Mammoto, Akiko and Chen, Jing}
}
@article {1538309,
	title = {Microglia-organized scar-free spinal cord repair in neonatal mice},
	journal = {Nature},
	volume = {587},
	number = {7835},
	year = {2020},
	month = {2020 Nov},
	pages = {613-618},
	abstract = {Spinal cord injury in mammals is thought to trigger scar formation with little regeneration of axons. Here we show that a crush injury to the spinal cord in neonatal mice leads to scar-free healing that permits the growth of long projecting axons through the lesion. Depletion of microglia in neonatal mice disrupts this healing process and stalls the regrowth of axons, suggesting that microglia are critical for orchestrating the injury response. Using single-cell RNA sequencing and functional analyses, we find that neonatal microglia are transiently activated and have at least two key roles in scar-free healing. First, they transiently secrete fibronectin and its binding proteins to form bridges of extracellular matrix that ligate the severed ends of the\&nbsp;spinal cord. Second, neonatal-but not adult-microglia express several extracellular and intracellular peptidase inhibitors, as well as other molecules that are involved in resolving inflammation. We transplanted either neonatal microglia or adult microglia treated with peptidase inhibitors into spinal cord lesions of adult mice, and found that both types of microglia significantly improved healing and axon regrowth. Together, our results reveal the cellular and molecular basis of\&nbsp;the nearly complete recovery of neonatal mice after spinal cord injury, and suggest strategies that could be used to facilitate scar-free healing in the adult mammalian nervous system.},
	issn = {1476-4687},
	doi = {10.1038/s41586-020-2795-6},
	author = {Li, Yi and He, Xuelian and Kawaguchi, Riki and Zhang, Yu and Wang, Qing and Monavarfeshani, Aboozar and Yang, Zhiyun and Chen, Bo and Shi, Zhongju and Meng, Huyan and Zhou, Songlin and Zhu, Junjie and Jacobi, Anne and Swarup, Vivek and Popovich, Phillip G and Geschwind, Daniel H and He, Zhigang}
}
@article {1179131,
	title = {Optic Nerve Head Characteristics in Chronic Angle Closure Glaucoma Detected by Swept-Source OCT},
	journal = {Curr Eye Res},
	volume = {42},
	number = {11},
	year = {2017},
	month = {2017 Nov},
	pages = {1450-1457},
	abstract = {PURPOSE: To compare structural features in prelaminar and laminar tissues of the optic nerve head (ONH) in chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG), and control subjects. MATERIALS AND METHODS: ONH imaging was performed using swept-source optical coherence tomography (SS-OCT) for measurements of minimum rim width at Bruch{\textquoteright}s membrane opening (BMO-MRW), horizontal, and vertical lamina cribrosa depth (LCD). Prelaminar defects, categorized as hole and wedge, and lamina cribrosa (LC) defects were identified. Enhanced depth imaging spectral domain OCT (EDI-OCT) customized to perform high-resolution volume scans was used in conjunction to further characterize prelaminar holes. One eye per subject was analyzed. RESULTS: Eighty subjects (20 CACG, 40 POAG, and 20 controls) were included in the study. CACG and POAG groups had similar mean deviation on Humphrey visual field testing (-6.9 {\textpm} 5.1 vs. -6.3 {\textpm} 6.0 dB, p \&gt; 0.05) and IOP on the day of imaging (14.0 {\textpm} 3.1 vs. 13.8 {\textpm} 2.7 mmHg, p \&gt; 0.05). Thinnest and global BMO-MRW in CACG (120.3 {\textpm} 44.8, 225.5 {\textpm} 53.9 μm) and POAG (109.7 {\textpm} 56.3, 213.8 {\textpm} 59.7 μm) groups were lower than controls (200.1 {\textpm} 40.8, 308.3 {\textpm} 70.8 μm; p \&lt; 0.001 for both). Prelaminar holes were most frequent in CACG (65.0\%) than POAG (25.0\%, p=0.008) or control groups (20.0\%, p=0.01). After adjusting for demographic and ophthalmic covariates, CACG was associated with increased odds of having prelaminar holes compared to POAG (odds ratio, 9.79; 95\% CI, 2.12-45.19; p=0.003). Hole volume was similar between CACG and POAG (p \&gt; 0.05), but the CACG group had more holes per scan than POAG (maximum 2.5 {\textpm} 1.9 vs. 1.2 {\textpm} 0.4, p=0.02). Prelaminar wedge defects were less common in the CACG than the POAG group (5.0\% vs. 37.5\%, p=0.02). The CACG group did not differ from controls in laminar characteristics, such as LCD and LC defects. CONCLUSIONS: SS-OCT evaluation of the ONH revealed more frequent prelaminar holes in CACG compared to POAG and control patients.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2017.1341535},
	author = {Li, Dejiao and Li, Taibo and Paschalis, Eleftherios I and Wang, Haobing and Taniguchi, Elise V and Choo, Zi-Ning and Shoji, Marissa K and Greenstein, Scott H and Brauner, Stacey C and Turalba, Angela V and Pasquale, Louis R and Shen, Lucy Q}
}
@article {1363142,
	title = {Resolvin D1 and aspirin-triggered resolvin D1 regulate histamine-stimulated conjunctival goblet cell secretion},
	journal = {Mucosal Immunol},
	volume = {6},
	number = {6},
	year = {2013},
	month = {2013 Nov},
	pages = {1119-30},
	abstract = {Resolution of inflammation is an active process mediated by pro-resolution lipid mediators. As resolvin (Rv) D1 is produced in the cornea, pro-resolution mediators could be effective in regulating inflammatory responses to histamine in allergic conjunctivitis. Two key mediators of resolution are the D-series resolvins RvD1 or aspirin-triggered RvD1 (AT-RvD1). We used cultured conjunctival goblet cells to determine whether histamine actions can be terminated during allergic responses. We found cross-talk between two types of G protein-coupled receptors (GPRs), as RvD1 interacts with its receptor GPR32 to block histamine-stimulated H1 receptor increases in intracellular [Ca(2+)] ([Ca(2+)]i) preventing H1 receptor-mediated responses. In human and rat conjunctival goblet cells, RvD1 and AT-RvD1 each block histamine-stimulated secretion by preventing its increase in [Ca(2+)]i and activation of extracellular regulated-protein kinase (ERK)1/2. We suggest that D-series resolvins regulate histamine responses in the eye and offer new treatment approaches for allergic conjunctivitis or other histamine-dependent pathologies.},
	keywords = {Animals, Aspirin, Bodily Secretions, Calcium Signaling, Cells, Cultured, Conjunctivitis, Allergic, Docosahexaenoic Acids, Extracellular Signal-Regulated MAP Kinases, Goblet Cells, Histamine, Histamine H1 Antagonists, Humans, Male, Rats, Rats, Sprague-Dawley, Receptor Cross-Talk, Receptors, G-Protein-Coupled, Receptors, Histamine H1},
	issn = {1935-3456},
	doi = {10.1038/mi.2013.7},
	author = {Li, D and Hodges, R R and Jiao, J and Carozza, R B and Shatos, M A and Chiang, N and Serhan, C N and Dartt, D A}
}
@article {1328893,
	title = {Mast cells contribute to the induction of ocular mucosal alloimmunity},
	journal = {Am J Transplant},
	volume = {19},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {662-673},
	abstract = {Beyond their historical role as the effector cells in allergic disorders, mast cells have been implicated in regulating both innate and adaptive immune responses. Possessing considerable functional plasticity, mast cells are abundant at mucosal surfaces, where the host and external environments interface. The purpose of this study was to evaluate the contribution of mast cells to allograft rejection at the ocular surface. Using a well-characterized murine model of corneal transplantation, we report that mast cells promote allosensitization. Our data show mast cell frequencies and activation are increased following transplantation. We demonstrate that mast cell inhibition (a) limits the infiltration of inflammatory cells and APC maturation at the graft site; (b) reduces allosensitization and the generation of Th1 cells in draining lymphoid tissues; (c) decreases graft infiltration of alloimmune-inflammatory cells; and (d) prolongs allograft survival. Our data demonstrate a novel function of mast cells in promoting allosensitization at the ocular surface.},
	issn = {1600-6143},
	doi = {10.1111/ajt.15084},
	author = {Li, Mingshun and Mittal, Sharad K and Foulsham, William and Amouzegar, Afsaneh and Sahu, Srikant K and Chauhan, Sunil K}
}
@article {705086,
	title = {Cost and Selection of Ophthalmic Anti-Vascular Endothelial Growth Factor Agents.},
	journal = {R I Med J (2013)},
	volume = {99},
	number = {5},
	year = {2016},
	month = {2016},
	pages = {15-7},
	abstract = {Anti-vascular endothelial growth factor (anti-VEGF) drugs - ranibizumab, aflibercept, and off-label bevacizumab - are vital to the treatment of common retinal diseases, including exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema (ME) associated with retinal vein occlusion (RVO). Given the high prevalence of AMD and retinal vascular diseases, anti-VEGF agents represent a large cost burden to the United States (US) healthcare system. Although ranibizumab and aflibercept are 30-fold more expensive per injection than bevacizumab, the two more costly medications are commonly used in the US, even though all three have been shown to be effective and safe for treatment of these retinal diseases. We investigated the availability and content of professional ophthalmic guidelines on cost consideration in the selection of anti-VEGF agents. We found that current professional guidelines were limited in availability and lacked specific guidance on cost-based anti-VEGF drug selection. This represents a missed opportunity to encourage the practice of value-based medicine. [Full article available at http://rimed.org/rimedicaljournal-2016-05.asp, free with no login].},
	issn = {2327-2228},
	author = {Li, Emily and Greenberg, Paul B and Voruganti, Indu and Krzystolik, Magdalena G}
}
@article {1593838,
	title = {Age, Gender, and Laterality of Retinal Vascular Occlusion: A Retrospective Study from the IRIS{\textregistered} Registry},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {2},
	year = {2022},
	month = {2022 02},
	pages = {161-171},
	abstract = {PURPOSE: Retinal vascular occlusion is a leading cause of profound irreversible visual loss, but the understanding of the disease is insufficient. We systematically investigated the age, gender, and laterality at the onset of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) in the Intelligent Research in Sight (IRIS{\textregistered}) Registry. DESIGN: Retrospective registry cohort. PARTICIPANTS: Patients with retinal vascular occlusion participating in the IRIS{\textregistered} Registry. METHODS: Patients who received a diagnosis of retinal vascular occlusion between 2013 and 2017 were included. Those with unspecified gender or laterality were excluded when conducting the relevant analyses. Patients were categorized into RAO, with subtypes transient retinal artery occlusion (TRAO), partial retinal artery occlusion (PRAO), branch retinal artery occlusion (BRAO), and central retinal artery occlusion (CRAO), and into RVO, with subtypes venous engorgement (VE), branch retinal vein occlusion (BRVO), and central retinal vein occlusion (CRVO). Age was evaluated as a categorical variable (5-year increments). We investigated the association of age, gender, and laterality with the onset frequency of retinal vascular occlusion subtypes. MAIN OUTCOME MEASURES: The frequency of onset of RAO and RVO subtypes by age, gender and laterality. RESULTS: A total of 1 251 476 patients with retinal vascular occlusion were included, 23.8\% of whom had RAO, whereas 76.2\% had RVO. Of these, 1 248 656 and 798 089 patients were selected for analyses relevant to gender and laterality, respectively. The onset frequency of all subtypes increased with age. PRAO, BRAO, CRAO, and CRVO presented more frequently in men (53.5\%, 51.3\%, 52.6\%, and 50.4\%, respectively), whereas TRAO, VE, and BRVO presented more frequently in women (54.9\%, 56.0\%, and 54.5\% respectively). All RAO subtypes and BRVO showed a right-eye onset preference (TRAO, 51.7\%; PRAO, 54.4\%; BRAO, 53.5\%; CRAO, 53.4\%; and BRVO, 51.0\%), whereas VE and CRVO exhibited a left-eye onset preference (53.3\% and 50.9\%, respectively). CONCLUSIONS: Although retinal vascular occlusion incidence increases with age regardless of subtypes, we found various subtype-specific disease-onset differences related to gender and, in particular, ocular laterality. These findings may improve understanding of the specific cause of retinal vascular occlusions of different subtypes and their relationships with structural and anatomic asymmetries of the vascular system.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2021.05.004},
	author = {Li, Yangjiani and Hall, Nathan E and Pershing, Suzann and Hyman, Leslie and Haller, Julia A and Lee, Aaron Y and Lee, Cecilia S and Chiang, Michael and Lum, Flora and Miller, Joan W and Lorch, Alice and Tobias Elze}
}
@article {416911,
	title = {A common variant near TGFBR3 is associated with primary open angle glaucoma.},
	journal = {Hum Mol Genet},
	volume = {24},
	number = {13},
	year = {2015},
	month = {2015 Jul 1},
	pages = {3880-92},
	abstract = {Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 {\texttimes} 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 {\texttimes} 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddv128},
	author = {Li, Zheng and Allingham, R Rand and Nakano, Masakazu and Jia, Liyun and Chen, Yuhong and Ikeda, Yoko and Mani, Baskaran and Chen, Li-Jia and Kee, Changwon and Garway-Heath, David F and Sripriya, Sarangapani and Fuse, Nobuo and Abu-Amero, Khaled K and Huang, Chukai and Namburi, Prasanthi and Burdon, Kathryn and Perera, Shamira A and Gharahkhani, Puya and Lin, Ying and Ueno, Morio and Ozaki, Mineo and Mizoguchi, Takanori and Krishnadas, Subbiah Ramasamy and Osman, Essam A and Lee, Mei Chin and Chan, Anita S Y and Tajudin, Liza-Sharmini A and Do, Tan and Goncalves, Aurelien and Reynier, Pascal and Zhang, Hong and Bourne, Rupert and Goh, David and Broadway, David and Husain, Rahat and Negi, Anil K and Daniel Hsu and Ho, Ching-Lin and Blanco, Augusto Azuara and Leung, Christopher K S and Wong, Tina T and Yakub, Azhany and Liu, Yutao and Nongpiur, Monisha E and Han, Jong Chul and Hon, Do Nhu and Shantha, Balekudaru and Zhao, Bowen and Sang, Jinghong and Zhang, Nihong and Ryuichi Sato and Yoshii, Kengo and Panda-Jonas, Songhomita and Ashley Koch, Allison E and Herndon, Leon W and Moroi, Sayoko E and Challa, Pratap and Foo, Jia Nee and Bei, Jin-Xin and Zeng, Yi-Xin and Simmons, Cameron P and Bich Chau, Tran Nguyen and Sharmila, Philomenadin Ferdinamarie and Chew, Merwyn and Lim, Blanche and Tam, Pansy O S and Chua, Elaine and Ng, Xiao Yu and Yong, Victor H K and Chong, Yaan Fun and Meah, Wee Yang and Vijayan, Saravanan and Seongsoo, Sohn and Xu, Wang and Teo, Yik Ying and Cooke Bailey, Jessica N and Kang, Jae H and Haines, Jonathan L and Cheng, Ching Yu and Saw, Seang-Mei and Tai, E-Shyong and ICAARE-Glaucoma Consortium and NEIGHBORHOOD Consortium and Richards, Julia E and Ritch, Robert and Gaasterland, Douglas E and Pasquale, Louis R and Liu, Jianjun and Jonas, Jost B and Milea, Dan and George, Ronnie and Al-Obeidan, Saleh A and Mori, Kazuhiko and Macgregor, Stuart and Hewitt, Alex W and Girkin, Christopher A and Zhang, Mingzhi and Sundaresan, Periasamy and Vijaya, Lingam and Mackey, David A and Wong, Tien Yin and Craig, Jamie E and Sun, Xinghuai and Kinoshita, Shigeru and Wiggs, Janey L and Khor, Chiea-Chuen and Yang, Zhenglin and Pang, Chi Pui and Wang, Ningli and Hauser, Michael A and Tashiro, Kei and Aung, Tin and Vithana, Eranga N}
}
@article {1698396,
	title = {Vitamin C protects retinal ganglion cells via SPP1 in glaucoma and after optic nerve damage},
	journal = {Life Sci Alliance},
	volume = {6},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	abstract = {Glaucoma is a common neurodegenerative disorder characterized by retinal ganglion cell death, astrocyte reactivity in the optic nerve, and vision loss. Currently, lowering the intraocular pressure (IOP) is the first-line treatment, but adjuvant neuroprotective approaches would be welcome. Vitamin C possesses neuroprotective activities that are thought to be related to its properties as a co-factor of enzymes and its antioxidant effects. Here, we show that vitamin C promotes a neuroprotective phenotype and increases gene expression related to neurotropic factors, phagocytosis, and mitochondrial ATP production. This effect is dependent on the up-regulation of secreted phosphoprotein 1 (SPP1) in reactive astrocytes via the transcription factor E2F1. SPP1+ astrocytes in turn promote retinal ganglion cell survival in a mouse model of glaucoma. In addition, oral administration of vitamin C lowers the IOP in mice. This study identifies an additional neuroprotective pathway for vitamin C and suggests a potential therapeutic role of vitamin C in neurodegenerative diseases such as glaucoma.},
	keywords = {Animals, Ascorbic Acid, Glaucoma, Mice, Optic Nerve, Osteopontin, Retinal Ganglion Cells},
	issn = {2575-1077},
	doi = {10.26508/lsa.202301976},
	author = {Li, Song and Jakobs, Tatjana C}
}
@article {1661838,
	title = {Secreted phosphoprotein 1 slows neurodegeneration and rescues visual function in mouse models of aging and glaucoma},
	journal = {Cell Rep},
	volume = {41},
	number = {13},
	year = {2022},
	month = {2022 Dec 27},
	pages = {111880},
	abstract = {Aging causes an irreversible, cumulative decline in neuronal function. Using the visual system as a model, we show that astrocytes play a critical role in maintaining retinal ganglion cell health and that deletion of SPP1 (secreted phosphoprotein 1, or osteopontin) from astrocytes leads to increased vulnerability of ganglion cells to age, elevated intraocular pressure, and traumatic optic nerve damage. Overexpression of SPP1 slows the age-related decline in ganglion cell numbers and is highly protective of visual function in a mouse model of glaucoma. SPP1 acts by promoting phagocytosis and secretion of neurotrophic factors while inhibiting production of neurotoxic and pro-inflammatory factors. SPP1 up-regulates transcription of genes related to oxidative phosphorylation, functionally enhances mitochondrial respiration, and promotes the integrity of mitochondrial microstructure. SPP1 increases intracellular ATP concentration via up-regulation of VDAC1.},
	keywords = {Aging, Animals, Glaucoma, Mice, Optic Nerve Injuries, Osteopontin, Retinal Ganglion Cells},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2022.111880},
	author = {Li, Song and Jakobs, Tatjana C}
}
@article {742271,
	title = {Comparison of swept-source and enhanced depth imaging spectral-domain optical coherence tomography in quantitative characterisation of the optic nerve head.},
	journal = {Br J Ophthalmol},
	year = {2016},
	month = {2016 Jun 13},
	abstract = {AIMS: To compare swept-source optical coherence tomography (SS-OCT) and enhanced depth imaging spectral-domain OCT (EDI-OCT) in quantitative assessment of optic nerve head (ONH) parameters. METHODS: In a cross-sectional study, patients with primary open angle glaucoma (POAG) and age-matched control subjects underwent SS-OCT and EDI-OCT B-scans of the ONH in a single visit. Two masked readers independently measured the horizontal and vertical lamina cribrosa depth (LCDH and LCDV, respectively), as well as thinnest Bruch{\textquoteright}s membrane opening minimum rim width (BMO-MRW) from SS-OCT and EDI-OCT scans. We assessed agreement between SS-OCT and EDI-OCT measurements by linear regression models, Bland-Altman analysis and concordance correlation coefficients (CCC). Intrareader and inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). RESULTS: One eye from each of 40 patients with POAG and 20 controls were included. All three ONH measurements were higher on SS-OCT than on EDI-OCT, with significant differences in LCDH (mean difference=31.7 {\textmu}m, p\&lt;0.01) and thinnest BMO-MRW (mean difference=20.5 {\textmu}m, p\&lt;0.01). Linear regression models described the agreement between SS-OCT and EDI-OCT measurements with R(2)\&gt;0.8 for LCDH among both patients with POAG and controls and for thinnest BMO-MRW among patients with POAG. The CCC was \&gt;0.8 overall for each parameter. Intrareader and inter-reader ICCs were >=0.989 and >=0.964, respectively, for all parameters. CONCLUSIONS: LCDH, LCDV and thinnest BMO-MRW measurements are not interchangeable between SS-OCT and EDI-OCT, but show good intrareader and inter-reader reproducibility and interdevice agreement for quantitative characterisation of the ONH, particularly among patients with glaucoma.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2016-308586},
	author = {Li, Dejiao and Taniguchi, Elise V and Cai, Sophie and Paschalis, Eleftherios I and Wang, Haobing and Miller, John B and Turalba, Angela V and Greenstein, Scott H and Brauner, Stacey and Pasquale, Louis R and Shen, Lucy Q}
}
@article {1363143,
	title = {Role of PKCα activation of Src, PI-3K/AKT, and ERK in EGF-stimulated proliferation of rat and human conjunctival goblet cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {8},
	year = {2013},
	month = {2013 Aug 21},
	pages = {5661-74},
	abstract = {PURPOSE: To determine the order and components of the signaling pathway utilized by epidermal growth factor (EGF) to stimulate conjunctival goblet cell proliferation. METHODS: Goblet cells from rat bulbar and forniceal conjunctiva and human bulbar conjunctiva were grown in organ culture. Goblet cells (GCs) were serum starved for 24 hours and preincubated with inhibitors for 30 minutes or small interfering RNA (siRNA) for 48 hours prior to addition of EGF. Proliferation was then measured or Western blot analysis was performed using antibodies against phosphorylated protein kinase B (AKT), extracellular signal-regulated kinase 1/2 (ERK1/2), or the non-receptor tyrosine kinase Src. Rat GCs were also incubated with adenoviruses expressing dominant negative protein kinase Cα (DNPKCα) or constitutively activated protein kinase Cα (myrPKCα), and activation of AKT and ERK1/2 was determined by Western blot analysis. RESULTS: Inhibitors of phosphoinositol-3 kinase (PI-3K)/AKT pathway blocked EGF-stimulated ERK1/2 activation and GC proliferation. Inhibitors of EGF-stimulated ERK1/2 activity did not inhibit AKT activation but blocked proliferation. DNPKCα blocked EGF-stimulated activation of AKT and ERK1/2 while myrPKCα increased activation of these kinases. Inhibitors of PI-3K, ERK1/2, and protein kinase C (PKC) blocked myrPKCα-stimulated GC proliferation. EGF and myrPKCα increased phosphorylation of Src, and inhibition of Src with the chemical inhibitor PP1 or siRNA inhibited EGF-stimulated GC proliferation. CONCLUSIONS: We found that EGF activates a major pathway to stimulate goblet cell proliferation. This pathway consists of induction of phospholipase C (PLC)γ to activate PKCα. Active PKCα phosphorylates Src to induce PI-3K to phosphorylate AKT that subsequently activates the ERK1/2 cascade to stimulate goblet cell proliferation.},
	keywords = {Animals, Cell Proliferation, Chromones, Conjunctiva, Enzyme Inhibitors, Epidermal Growth Factor, Goblet Cells, Humans, Male, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 1, Morpholines, Organ Culture Techniques, Phosphatidylinositol 3-Kinases, Phosphorylation, Primary Cell Culture, Protein Kinase C-alpha, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins pp60(c-src), Rats, Rats, Sprague-Dawley, RNA, Small Interfering},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12473},
	author = {Li, Dayu and Shatos, Marie A and Hodges, Robin R and Dartt, Darlene A.}
}
@article {1498259,
	title = {Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa},
	journal = {Gene Ther},
	volume = {28},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {223-241},
	abstract = {Recent advances in viral vector engineering, as well as an increased understanding of the cellular and molecular mechanism of retinal diseases, have led to the development of novel gene therapy approaches. Furthermore, ease of accessibility and ocular immune privilege makes the retina an ideal target for gene therapies. In this study, the nuclear hormone receptor gene Nr2e3 was evaluated for efficacy as broad-spectrum therapy to attenuate early to intermediate stages of retinal degeneration in five unique mouse models of retinitis pigmentosa (RP). RP is a group of heterogenic inherited retinal diseases associated with over 150 gene mutations, affecting over 1.5 million individuals worldwide. RP varies in age of onset, severity, and rate of progression. In addition, ~40\% of RP patients cannot be genetically diagnosed, confounding the ability to develop personalized RP therapies. Remarkably, Nr2e3 administered therapy resulted in reduced retinal degeneration as observed by increase in photoreceptor cells, improved electroretinogram, and a dramatic molecular reset of key transcription factors and associated gene networks. These therapeutic effects improved retinal homeostasis in diseased tissue. Results of this study provide evidence that Nr2e3 can serve as a broad-spectrum therapy to treat multiple forms of RP.},
	issn = {1476-5462},
	doi = {10.1038/s41434-020-0134-z},
	author = {Li, Sujun and Datta, Shyamtanu and Brabbit, Emily and Love, Zoe and Woytowicz, Victoria and Flattery, Kyle and Capri, Jessica and Yao, Katie and Wu, Siqi and Imboden, Michael and Upadhyay, Arun and Arumugham, Rasappa and Thoreson, Wallace B and Deangelis, Margaret M and Haider, Neena B}
}
@article {987996,
	title = {Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	number = {2},
	year = {2017},
	pages = {E209-E218},
	abstract = {Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn(2+) accumulation in amacrine cell processes involves the Zn(2+) transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn(2+) chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn(2+) chelation extends for several days after nerve injury. These results show that retinal Zn(2+) dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn(2+) chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1616811114},
	author = {Li, Yiqing and Andereggen, Lukas and Yuki, Kenya and Omura, Kumiko and Yin, Yuqin and Gilbert, Hui-Ya and Erdogan, Burcu and Asdourian, Maria S and Shrock, Christine and de Lima, Silmara and Apfel, Ulf-Peter and Zhuo, Yehong and Hershfinkel, Michal and Lippard, Stephen J and Rosenberg, Paul A and Benowitz, Larry}
}
@article {1328894,
	title = {Thyroid eye disease: what is new to know?},
	journal = {Curr Opin Ophthalmol},
	volume = {29},
	number = {6},
	year = {2018},
	month = {2018 Nov},
	pages = {528-534},
	abstract = {PURPOSE OF REVIEW: The pathophysiology of thyroid eye disease (TED) is still not fully understood. However, recently described risk factors and molecular findings have brought new insights into the mechanisms of TED and could lead to the emerging use of more targeted therapies. This article aims to review the clinical findings of TED, and the most recent advances in our understanding of the risk factors and therapeutic options for TED. RECENT FINDINGS: Smoking has been recently shown to have an impact on specific gene expression involved in several disease-related pathways, which seems to be reversible with smoking cessation. This finding further emphasizes the importance of smoking cessation in the prevention and treatment of TED. Selenium deficiency and high-serum cholesterol have been described to be potential independent risk factors for TED and their management could decrease the incidence and severity of TED. In terms of therapeutic options, immunomodulatory medications have shown some promising results for disease control in TED over the past years, but further randomized prospective studies with larger sample sizes are still needed to prove their efficacy. A new technique of P brachytherapy was shown to have quick therapeutic effects on TED without significant side effects and could be a promising therapy for selected cases of TED. SUMMARY: TED is one of the most common autoimmune inflammatory disorders of the orbit. Although its pathophysiology remains unclear, newly described genetic findings and risk factors could help in explaining its occurrence and guide future therapies. Immunosuppressant medications are increasingly used in the management of TED, but further studies are needed to confirm their effectiveness.},
	keywords = {Brachytherapy, Graves Ophthalmopathy, Humans, Immunomodulation, Phosphorus Radioisotopes, Risk Factors, Smoking Cessation},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000529},
	author = {Li, Zhen and Cestari, Dean M and Fortin, Elizabeth}
}
@article {1424807,
	title = {Emerging roles for insulin-like growth factor binding protein like protein 1},
	journal = {Neural Regen Res},
	volume = {14},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {258-259},
	issn = {1673-5374},
	doi = {10.4103/1673-5374.244787},
	author = {Li, Yingqian and Zhao, Eric and Chen, Dong Feng}
}
@article {1647869,
	title = {The Predictive Potential of Altered Voxel-Based Morphometry in Severely Obese Patients With Meibomian Gland Dysfunction},
	journal = {Front Neurosci},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {939268},
	abstract = {Objective: To investigate voxel-based morphometry (VBM) by using magnetic resonance imaging (MRI) in meibomian gland dysfunction patients with severe obesity (PATs) and to explore the application of VBM in the early diagnosis, prevention of cognitive impairment and targeted treatment of this disease. Methods: Sixteen PATs and 12 healthy controls (HCs) were enrolled and underwent MRI. Whole-head images were analyzed using VBM and data were compared between groups using an independent samples t-test. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic value of this approach. Mini-mental state examination (MMSE) scores were used to assess cognitive impairment and were analyzed using an independent samples t-test. Results: Compared with HCs, the VBM values in PATs were reduced in the left cerebellum and right thalamus but increased in the right brainstem, right precuneus and right paracentral lobule. The results of ROC curve analysis indicated that VBM may be useful in meibomian gland disease diagnosis. Comparison of MMSE scores between groups showed mild cognitive impairment in PATs. Conclusion: PATs showed altered VBM values in some brain areas. These findings may provide information about the pathophysiology of meibomian gland dysfunction and may help to explain the underlying mechanisms of clinical manifestations in PATs, such as cognitive impairment. Abnormal VBM values in these brain areas may serve as predictive factors for development of meibomian gland disease in severely obese people and as indicators for individualized treatment.},
	issn = {1662-4548},
	doi = {10.3389/fnins.2022.939268},
	author = {Li, Le-Yan and Wang, Yuan-Yuan and Gao, Jun-Wei and Chen, Jun and Kang, Min and Ying, Ping and Liao, Xu Lin and Wang, Yixin and Zou, Jie and Su, Ting and Wei, Hong and Shao, Yi}
}
@article {1661822,
	title = {High Positive Predictive Value of Fluorescein Angiography Contiguous, Perineural Retinal Vascular Leakage Pattern for Birdshot Chorioretinopathy},
	journal = {Ocul Immunol Inflamm},
	volume = {32},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {48-53},
	abstract = {PURPOSE: To determine the sensitivity and positive predictive value (PPV) of a contiguous, perineural retinal vascular leakage fluorescein angiography (FA) pattern in birdshot chorioretinopathy (BSCR) patients.

METHODS: Patients with BSCR and other posterior uveitis/retinal vasculitis and a FA were identified. Two graders reviewed the first FA for leakage primarily around the optic nerve and along the larger arcade vessels. We compared the rates of this pattern in BSCR and non-BSCR patients and calculated sensitivity and PPV. We compared clinical characteristics of BSCR patients with and without this pattern.

RESULTS: 64 BSCR and 98 non-BSCR patients were identified. The FA pattern{\textquoteright}s sensitivity, specificity, and PPV were 57.8\%, 91.8\%, and 82.2\%. This pattern was significantly more common in BSCR patients earlier in their disease (p =~.004).

CONCLUSIONS: A contiguous, perineural retinal vascular leakage FA pattern can help identify potential BSCR patients for further testing. This pattern is more common closer to symptom onset.},
	keywords = {Birdshot Chorioretinopathy, Chorioretinitis, Fluorescein Angiography, Humans, Predictive Value of Tests, Uveitis, Posterior},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2150228},
	author = {Li, Ashley and Apivatthakakul, Atitaya and Papaliodis, George N and Sobrin, Lucia}
}
@article {1517167,
	title = {Lutein Supplementation for Eye Diseases},
	journal = {Nutrients},
	volume = {12},
	number = {6},
	year = {2020},
	month = {2020 Jun 09},
	abstract = {Lutein is one of the few xanthophyll carotenoids that is found in high concentration in the macula of human retina. As synthesis of lutein within the human body is impossible, lutein can only be obtained from diet. It is a natural substance abundant in egg yolk and dark green leafy vegetables. Many basic and clinical studies have reported lutein{\textquoteright}s anti-oxidative and anti-inflammatory properties in the eye, suggesting its beneficial effects on protection and alleviation of ocular diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, myopia, and cataract. Most importantly, lutein is categorized as Generally Regarded as Safe (GRAS), posing minimal side-effects upon long term consumption. In this review, we will discuss the chemical structure and properties of lutein as well as its application and safety as a nutritional supplement. Finally, the effects of lutein consumption on the aforementioned eye diseases will be reviewed.},
	issn = {2072-6643},
	doi = {10.3390/nu12061721},
	author = {Li, Long Hin and Lee, Jetty Chung-Yung and Leung, Ho Hang and Lam, Wai Ching and Fu, Zhongjie and Lo, Amy Cheuk Yin}
}
@article {1629447,
	title = {Computational investigation of blood cell transport in retinal microaneurysms},
	journal = {PLoS Comput Biol},
	volume = {18},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {e1009728},
	abstract = {Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). MA leakage or rupture may precipitate local pathology in the surrounding neural retina that impacts visual function. Thrombosis in MAs may affect their turnover time, an indicator associated with visual and anatomic outcomes in the diabetic eyes. In this work, we perform computational modeling of blood flow in microchannels containing various MAs to investigate the pathologies of MAs in DR. The particle-based model employed in this study can explicitly represent red blood cells (RBCs) and platelets as well as their interaction in the blood flow, a process that is very difficult to observe in vivo. Our simulations illustrate that while the main blood flow from the parent vessels can perfuse the entire lumen of MAs with small body-to-neck ratio (BNR), it can only perfuse part of the lumen in MAs with large BNR, particularly at a low hematocrit level, leading to possible hypoxic conditions inside MAs. We also quantify the impacts of the size of MAs, blood flow velocity, hematocrit and RBC stiffness and adhesion on the likelihood of platelets entering MAs as well as their residence time inside, two factors that are thought to be associated with thrombus formation in MAs. Our results show that enlarged MA size, increased blood velocity and hematocrit in the parent vessel of MAs as well as the RBC-RBC adhesion promote the migration of platelets into MAs and also prolong their residence time, thereby increasing the propensity of thrombosis within MAs. Overall, our work suggests that computational simulations using particle-based models can help to understand the microvascular pathology pertaining to MAs in DR and provide insights to stimulate and steer new experimental and computational studies in this area.},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1009728},
	author = {He Li and Deng, Yixiang and Sampani, Konstantina and Cai, Shengze and Li, Zhen and Sun, Jennifer K and Karniadakis, George E}
}
@article {1363144,
	title = {Effect of VIP on intracellular [Ca2+], extracellular regulated kinase 1/2, and secretion in cultured rat conjunctival goblet cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {4},
	year = {2013},
	month = {2013 Apr 23},
	pages = {2872-84},
	abstract = {PURPOSE: To determine the intracellular signaling pathways that vasoactive intestinal peptide (VIP) uses to stimulate high molecular weight glycoconjugate secretion from cultured rat conjunctival goblet cells. METHODS: Goblet cells from rat bulbar and forniceal conjunctiva were grown in organ culture. Presence and localization of VIP receptors (VPAC1 and 2) were determined by RT-PCR, immunofluorescence microscopy and Western blot analysis. Intracellular [Ca(2+)] ([Ca(2+)]i) was measured using fura-2. Extracellular signal-regulated kinase (ERK)-1/2 activity was determined by Western blot analysis. High molecular weight glycoconjugate secretion was measured with an enzyme-linked lectin assay on cultured goblet cells that were serum-starved for 2 hours before stimulation with VIP, VPAC1-, or VPAC2-specific agonists. Inhibitors were added 30 minutes prior to VIP. Activation of epidermal growth factor receptor (EGFR) was measured by immunoprecipitation using an antibody against pTyr followed by Western blot analysis with an antibody against EGFR. RESULTS: Both VIP receptors were present in rat conjunctiva and cultured goblet cells. VIP- and VPAC-specific agonists increased [Ca(2+)]i and secretion in a concentration-dependent manner. VIP also increased ERK1/2 activity, VIP-stimulated increase in [Ca(2+)]i. Secretion, but not ERK1/2 activity, was inhibited by the protein kinase A inhibitor, H89. VIP-stimulated secretion was inhibited by siRNA for ERK2 but not by siRNA for EGFR. VIP did not increase the phosphorylation of the EGFR. CONCLUSIONS: In conclusion, in cultured rat conjunctival goblet cells, VPAC1 and 2 receptors are functional. VIP stimulates a cAMP-dependent increase in [Ca(2+)]i and glycoconjugate secretion, but not ERK1/2 activation. VIP does not activate with EGFR.},
	keywords = {Animals, Calcium, Cells, Cultured, Conjunctiva, Cyclic AMP-Dependent Protein Kinases, DNA, Complementary, Glycoconjugates, Goblet Cells, Male, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mucin 5AC, Organ Culture Techniques, Parasympathetic Nervous System, Rats, Rats, Sprague-Dawley, Receptors, Vasoactive Intestinal Peptide, Type II, Receptors, Vasoactive Intestinal Polypeptide, Type I, Vasoactive Intestinal Peptide},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-11264},
	author = {Li, Dayu and Jiao, Jianwei and Shatos, Marie A and Hodges, Robin R and Dartt, Darlene A.}
}
@article {1638554,
	title = {Sleep deprivation induces corneal epithelial progenitor cell over-expansion through disruption of redox homeostasis in the tear film},
	journal = {Stem Cell Reports},
	volume = {17},
	number = {5},
	year = {2022},
	month = {2022 May 10},
	pages = {1105-1119},
	abstract = {Sleep deficiency, a common public health problem, causes ocular discomfort and affects ocular surface health. However, the underlying mechanism remains unclear. Herein, we identified that short-term sleep deprivation (SD) resulted in hyperproliferation of corneal epithelial progenitor cells (CEPCs) in mice. The expression levels of p63 and Keratin 14, the biomarkers of CEPCs, were upregulated in the corneal epithelium after short-term SD. In addition, SD led to elevated levels of reactive oxygen species (ROS), and subsequent decrease in antioxidant capacity, in the tear film. Exogenous hydrogen peroxide (H2O2) could directly stimulate the proliferation of CEPCs in\&nbsp;vivo and in\&nbsp;vitro. Topical treatment of antioxidant L-glutathione preserved the over-proliferation of CEPCs and attenuated corneal epithelial defects in SD mice. Moreover, the activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is essential to ROS-stimulated cell proliferation in CEPCs. However, long-term SD ultimately led to early manifestation of limbal stem cell deficiency.},
	keywords = {Animals, Antioxidants, Cell Proliferation, Epithelium, Corneal, Homeostasis, Hydrogen Peroxide, Mice, Oxidation-Reduction, Phosphatidylinositol 3-Kinases, Reactive Oxygen Species, Sleep Deprivation, Stem Cells},
	issn = {2213-6711},
	doi = {10.1016/j.stemcr.2022.03.017},
	author = {Li, Sanming and Tang, Liying and Zhou, Jing and Anchouche, Sonia and Li, Dian and Yang, Yiran and Liu, Zhaolin and Wu, Jieli and Hu, Jiaoyue and Zhou, Yueping and Yin, Jia and Liu, Zuguo and Li, Wei}
}
@article {1364506,
	title = {Effect of histamine on Ca(2+)-dependent signaling pathways in rat conjunctival goblet cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {11},
	year = {2012},
	month = {2012 Oct 05},
	pages = {6928-38},
	abstract = {PURPOSE: The purpose of this study was to determine the Ca(2+)-dependent cellular signaling pathways used by histamine to stimulate conjunctival goblet cell secretion. METHODS: Cultured rat goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugates was measured by an enzyme-linked lectin assay. Intracellular [Ca(2+)] ([Ca(2+)](i)) was measured by loading cultured cells with the Ca(2+) sensitive dye fura-2. The level of [Ca(2+)](i) was measured using fluorescence microscopy. Extracellular regulated kinase (ERK) 2 was depleted using small interfering RNA (siRNA). RESULTS: Histamine-stimulated conjunctival goblet cell secretion of high molecular weight glycoproteins was blocked by removal of extracellular Ca(2+) and depletion of ERK2 by siRNA. Histamine increase in [Ca(2+)](i) was desensitized by repeated addition of agonist and blocked by a phospholipase C antagonist. Histamine at higher doses increased [Ca(2+)](i) by stimulating influx of extracellular Ca(2+), but at a lower dose released Ca(2+) from intracellular stores. Activation of each histamine receptor subtype (H(1)-H(4)) increased [Ca(2+)](i) and histamine stimulation was blocked by antagonists of each receptor subtype. The H(2) receptor subtype increase in [Ca(2+)](i) was cAMP dependent. CONCLUSIONS: We conclude that histamine activates phospholipase C to release intracellular Ca(2+) that induces the influx of extracellular Ca(2+) and activates ERK1/2 to stimulate conjunctival goblet cell mucous secretion, and that activation of all four histamine receptor subtypes can increase [Ca(2+)](i).},
	keywords = {Animals, Calcium, Calcium Signaling, Cells, Cultured, Conjunctiva, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Fura-2, Goblet Cells, Histamine, Histamine Agonists, Histamine Antagonists, Male, MAP Kinase Signaling System, Microscopy, Fluorescence, Mucins, Rats, Rats, Sprague-Dawley, Receptors, Histamine, RNA, Small Interfering, Type C Phospholipases},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-10163},
	author = {Li, Dayu and Carozza, Richard B and Shatos, Marie A and Hodges, Robin R and Dartt, Darlene A.}
}
@article {1658675,
	title = {Prevalence and Ocular Biometric Characteristics of Myopia in Primary Angle Closure Disease in Rural China: The Handan Eye Study},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {63},
	number = {12},
	year = {2022},
	month = {2022 Nov 01},
	pages = {19},
	abstract = {PURPOSE: The purpose of this study was to determine the prevalence of myopia among patients with primary angle closure disease (PACD) in rural China and their ocular biometric characteristics. METHODS: Study subjects were recruited from the Handan Eye Study. A/B-mode scan (Cine Scan, Quantel Medical, Cedex, France) was used to measure the axial length, anterior chamber depth (ACD), and lens thickness (LT). PACD was defined as the anterior chamber angle being considered closed when 180 degrees or more of the posterior pigmented trabecular meshwork were not visible on the gonioscopy. Myopia was defined as a spherical equivalent (SE) refractive error <=-0.5 diopter (D). Persons who did not meet PACD definition were classified as the open-angle (OA) group. RESULTS: The overall prevalence of myopia in persons with PACD was 13.7\% (11.6\% in primary angle closure suspect [PACS], 21.6\% in primary angle closure [PAC], 62.5\% in primary angle closure glaucoma [PACG]). The age-specific prevalence of myopia in PACD eyes was 41.7\% at 30 to 39 years old, 12.3\% at 40 to 49 years old, 8.7\% at 50 to 59 years old, 10.7\% at 60 to 69 years old, and 31.7\% at age 70 years and over. PACD had shorter AL (22.2 {\textpm} 0.8 vs. 22.9 {\textpm} 0.9\&nbsp;mm, P \&lt; 0.001), shallower ACD (2.3 {\textpm} 0.3 vs. 2.8 {\textpm} 0.4\&nbsp;mm, P \&lt; 0.001), and greater LT (5.0 {\textpm} 0.5 vs. 4.7 {\textpm} 0.5\&nbsp;mm, P \&lt; 0.001). PACD had even thicker lenses and deeper ACD with age than those with OA (all P <= 0.025) from 30 years to 70 years of age and over. CONCLUSIONS: Myopia was common among persons with PACD who were less than 40 years of age in this rural Chinese population, and over half of those with PACG were myopic.},
	keywords = {Adult, Aged, Biometry, China, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Middle Aged, Myopia, Prevalence},
	issn = {1552-5783},
	doi = {10.1167/iovs.63.12.19},
	author = {Liang, Yuan Bo and Shen, Ruyue and Zhou, Weihe and Fan, Sujie and Chan, Poemen P and Tham, Clement C Y and Congdon, Nathan and Friedman, David S and Wang, Ningli}
}
@article {1709751,
	title = {A multi-omics atlas of the human retina at single-cell resolution},
	journal = {Cell Genom},
	volume = {3},
	number = {6},
	year = {2023},
	month = {2023 Jun 14},
	pages = {100298},
	abstract = {Cell classes in the human retina are highly heterogeneous with their abundance varying by several orders of\&nbsp;magnitude. Here, we generated and integrated a multi-omics single-cell atlas of the adult human retina, including more than 250,000 nuclei for single-nuclei RNA-seq and 137,000 nuclei for single-nuclei ATAC-seq. Cross-species comparison of the retina atlas among human, monkey, mice, and chicken revealed relatively conserved and non-conserved types. Interestingly, the overall cell heterogeneity in primate retina decreases compared with that of rodent and chicken retina. Through integrative analysis, we identified 35,000 distal cis-element-gene pairs, constructed transcription factor (TF)-target regulons for more than 200 TFs, and partitioned the TFs into distinct co-active modules. We also revealed the heterogeneity of the cis-element-gene relationships in different cell types, even from the same class. Taken together, we present a comprehensive single-cell multi-omics atlas of the human retina as a resource that enables systematic molecular characterization at individual cell-type resolution.},
	issn = {2666-979X},
	doi = {10.1016/j.xgen.2023.100298},
	author = {Liang, Qingnan and Cheng, Xuesen and Wang, Jun and Owen, Leah and Shakoor, Akbar and Lillvis, John L and Zhang, Charles and Farkas, Michael and Kim, Ivana K and Li, Yumei and DeAngelis, Margaret and Chen, Rui}
}
@article {1511475,
	title = {Long-term effect of YAG laser iridotomy on corneal endothelium in primary angle closure suspects: a 72-month randomised controlled study},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {3},
	year = {2021},
	month = {2021 Mar},
	pages = {348-353},
	abstract = {PURPOSES: To evaluate the effect of YAG laser peripheral iridotomy (LPI) on corneal endothelial cell density (ECD) and morphology in primary angle closure suspects (PACS) over 72 months. METHODS: The Zhongshan Angle Closure Prevention Trial is a single-centre randomised controlled trial. Subjects with bilateral PACS received YAG LPI prophylactic treatment in one eye randomly, while the fellow eye served as control. Central corneal ECD and morphology were assessed using non-contact specular microscopy (SP-2000P, Topcon) at baseline, 6, 18, 36, 54 and 72 months postoperatively. Mixed model analysis was conducted to compare the difference between treated and fellow eyes. RESULTS: A total of 875 participants were included, with a mean age of 59.3{\textpm}5.0 years and 83.5\% female. The ECD declined significantly (p\&lt;0.001) over time in both treated and fellow eyes, but the treated eyes showed more progressive cell loss with increasing time (p\&lt;0.001). The difference in ECD loss between LPI-treated and fellow eyes was not significant at each follow-up until 72 months (4.9\% in LPI eyes vs 4.2\% in non-LPI eyes, p=0.003). Mean cell areas increased significantly over time in both treated and fellow eyes (p\&lt;0.001), but no longitudinal change was observed for hexagonality. In LPI-treated eyes, no significant correlation was found between age, gender, ocular biometrics, intraocular pressure and laser settings with endothelium change, except for time effect (p\&lt;0.01). CONCLUSION: ECD decreases over time primarily due to ageing effect. YAG LPI does not appear to cause clinically significant corneal endothelial damage over 72 months after treatment. TRIAL REGISTRATION NUMBER: ISRCTN45213099.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-315811},
	author = {Liao, Chimei and Zhang, Jian and Jiang, Yuzhen and Huang, Shengsong and Aung, Tin and Foster, Paul J and Friedman, David and He, Mingguang}
}
@article {1748361,
	title = {Investigation of Altered Spontaneous Brain Activity Patterns in Herpes Zoster Keratitis Using the Percent Amplitude of Fluctuation Method: A Resting-State Functional Magnetic Resonance Imaging Study},
	journal = {Neuropsychiatr Dis Treat},
	volume = {19},
	year = {2023},
	month = {2023},
	pages = {1781-1789},
	abstract = {PURPOSE: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients. METHODS: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity. RESULTS: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients{\textquoteright} anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus. CONCLUSION: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.},
	issn = {1176-6328},
	doi = {10.2147/NDT.S412516},
	author = {Liao, Xu Lin and Li, Chu Qi and Ge, Qian Min and Tang, Liying and Su, Ting and Li, Qiu Yu and Pan, Yi Cong and Shu, Hui Ye and Zhang, Li Juan and Shao, Yi}
}
@article {1698416,
	title = {Iris volume change with physiologic mydriasis to identify development of angle closure: the Zhongshan Angle Closure Prevention Trial},
	journal = {Br J Ophthalmol},
	volume = {108},
	number = {3},
	year = {2024},
	month = {2024 Feb 21},
	pages = {366-371},
	abstract = {AIMS: To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects. METHODS: Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression. RESULTS: A mean 16.8\% decrease in Iarea and a mean 6.26\% decrease in VOL occurred with pupil dilation, while 22.96\% non-progressors and 40\% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 {\textmu}m from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement). CONCLUSION: A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease. TRIAL REGISTRATION NUMBER: ISRCTN45213099.},
	keywords = {Anterior Eye Segment, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Iris, Mydriasis, Tomography, Optical Coherence},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-322981},
	author = {Liao, Chimei and Quigley, Harry and Jiang, Yuzhen and Huang, Shengsong and Huang, Wenyong and Friedman, David and Foster, Paul J and He, Mingguang}
}
@article {1323933,
	title = {Long-Term Colonization Dynamics of Enterococcus faecalis in Implanted Devices in Research Macaques},
	journal = {Appl Environ Microbiol},
	volume = {84},
	number = {18},
	year = {2018},
	month = {2018 Sep 15},
	abstract = {is a common opportunistic pathogen that colonizes cephalic recording chambers (CRCs) of macaques used in cognitive neuroscience research. We previously characterized 15 strains isolated from macaques at the Massachusetts Institute of Technology (MIT) in 2011. The goal of this study was to examine how a 2014 protocol change prohibiting the use of antimicrobials within CRCs affected colonizing strains. We collected 20 isolates from 10 macaques between 2013 and 2017 for comparison to 4 isolates previously characterized in 2011 with respect to the sequence type (ST) distribution, antimicrobial resistance, biofilm formation, and changes in genes that might confer a survival advantage. ST4 and ST55 were predominant among the isolates characterized in 2011, whereas the less antimicrobial-resistant lineage ST48 emerged to dominance after 2013. Two macaques remained colonized by ST4 and ST55 strains for 5 and 4 years, respectively. While the antimicrobial resistance and virulence factors identified in these ST4 and ST55 strains remained relatively stable, we detected an increase in biofilm formation ability over time in both isolates. We also found that ST48 strains were typically robust biofilm formers, which could explain why this ST increased in prevalence. Finally, we identified mutations in the DNA mismatch repair genes and in separate ST55 and ST4 strains and confirmed that strains bearing these mutations displayed a hypermutator phenotype. The presence of a hypermutator phenotype may complicate future antimicrobial treatment for clinically relevant infections in macaques. is a common cause of health care-associated infections in humans, largely due to its ability to persist in the hospital environment, colonize patients, acquire antimicrobial resistance, and form biofilms. Understanding how enterococci evolve in health care settings provides insight into factors affecting enterococcal survival and persistence. Macaques used in neuroscience research have long-term cranial implants that, despite best practices, often become colonized by This provides a unique opportunity to noninvasively examine the evolution of enterococci on a long-term indwelling device. We collected strains from cephalic implants over a 7-year period and characterized the sequence type, antimicrobial resistance, virulence factors, biofilm production, and hypermutator phenotypes. Improved antimicrobial stewardship allowed a less-antimicrobial-resistant strain to predominate at the implant interface, potentially improving antimicrobial treatment outcomes if future clinical infections occur. Biofilm formation appears to play an important role in the persistence of the strains associated with these implants.},
	issn = {1098-5336},
	doi = {10.1128/AEM.01336-18},
	author = {Lieberman, Mia T and Van Tyne, Daria and Dzink-Fox, JoAnn and Ma, Eric J and Gilmore, Michael S and Fox, James G}
}
@article {1677851,
	title = {Detecting disease progression in mild, moderate and severe glaucoma},
	journal = {Curr Opin Ophthalmol},
	volume = {34},
	number = {2},
	year = {2023},
	month = {2023 Mar 01},
	pages = {168-175},
	abstract = {PURPOSE OF REVIEW: The purpose of this review is to examine contemporary techniques for detecting the progression of glaucoma. We provide a general overview of detection principles and review evidence-based diagnostic strategies and specific considerations for detecting glaucomatous progression in patients with mild, moderate and severe disease. RECENT FINDINGS: Diagnostic techniques and technologies for glaucoma have dramatically evolved in recent years, affording clinicians an expansive toolkit with which to detect glaucoma progression. Each stage of glaucoma, however, presents unique diagnostic challenges. In mild disease, either structural or functional changes can develop first in disease progression. In moderate disease, structural or functional changes can occur either in tandem or in isolation. In severe disease, standard techniques may fail to detect further disease progression, but such detection can still be measured using other modalities. SUMMARY: Detecting disease progression is central to the management of glaucoma. Glaucomatous progression has both structural and functional elements, both of which must be carefully monitored at all disease stages to determine when interventions are warranted.},
	keywords = {Disease Progression, Glaucoma, Humans},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000925},
	author = {Liebman, Daniel L and Wen, Joanne C and Shen, Lucy Q}
}
@article {1798411,
	title = {Cauterization-mediated restriction from penetrating orbital trauma},
	journal = {J AAPOS},
	volume = {28},
	number = {1},
	year = {2024},
	month = {2024 Feb},
	pages = {103805},
	abstract = {A healthy 32-year-old woman presented with binocular diplopia immediately after sustaining a penetrating injury to the left periocular adnexa with a hot metal skewer. Examination revealed an incomitant esotropia, with complete limitation of abduction of the left eye with downshoot in left gaze and normal afferent visual function. Computed tomography and magnetic resonance imaging demonstrated no fracture, but there was mild thickening of the medial rectus muscle and associated fat stranding. Lack of orbitomuscular tethering or hematoma led to the presumptive diagnosis of thermal cauterization injury causing left medial rectus restriction. Given the lack of literature on this mechanism of injury, the patient was monitored closely. She exhibited remarkable spontaneous improvement in motility over 6 months, with near orthophoria in primary gaze. However, bothersome residual esotropic diplopia in left gaze prompted a left medial rectus recession, with a good outcome. This case demonstrates that isolated extraocular muscle thermal injuries and consequential strabismus can recover spontaneously; longitudinal observation before surgical intervention may be appropriate in such cases.},
	keywords = {Adult, Diplopia, Esotropia, Eye Injuries, Female, Humans, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Strabismus, Vision, Binocular},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.11.008},
	author = {Liebman, Daniel L and Weinert, Marguerite C and Dohlman, Jenny C and Hennein, Lauren and Gaier, Eric D}
}
@article {1645479,
	title = {Optic Perineuritis Associated With Cryptococcal Meningitis Presenting With a "Hot Orbit" in a Patient With Chronic Lymphocytic Leukemia},
	journal = {J Neuroophthalmol},
	volume = {42},
	number = {2},
	year = {2022},
	month = {2022 06 01},
	pages = {272-277},
	abstract = {ABSTRACT: A 75-year-old man presented with 3 days of progressive left retro-orbital pain, eyelid swelling, tearing, and pain with extraocular movement. His medical history was significant for type II diabetes mellitus and chronic lymphocytic leukemia, stable on no therapy since diagnosis 8 years prior. The initial examination was significant for diffuse restriction of left ocular motility, marked lid edema, and mild dyschromatopsia. Computed tomography demonstrated asymmetric left periorbital soft tissue swelling and intraconal fat stranding with an irregular left optic nerve sheath complex and clear paranasal sinuses. He was hospitalized for orbital cellulitis and treated empirically with broad-spectrum intravenous antibiotics, but his visual acuity declined over the ensuing 2 days. Subsequent MRI demonstrated left-greater-than-right circumferential optic nerve sheath enhancement, and leptomeningeal enhancement. An orbital biopsy demonstrated monoclonal B-cell lymphocyte aggregation, whereas a lumbar puncture was positive for Cryptococcus antigen with subsequent demonstration of abundant Cryptococcus by Papanicolaou stain. The final diagnosis was optic perineuritis secondary to cryptococcal meningitis presenting with orbital inflammation. Although his clinical course was complicated by immune reconstitution inflammatory syndrome, symptoms and signs of optic neuropathy ultimately resolved after 1 month of intensive antifungal therapy.},
	keywords = {Aged, Diabetes Mellitus, Type 2, Edema, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Meningitis, Cryptococcal, Orbit, Pain, Vision Disorders},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001538},
	author = {Liebman, Daniel L and Tam, Emily K and Lithgow, Marie Y and Kane, Joseph E and Fischbein, Nancy J and Lefebvre, Daniel R and Chwalisz, Bart K and Gaier, Eric D}
}
@article {1522743,
	title = {Quantifying the educational benefit of additional cataract surgery cases in ophthalmology residency},
	journal = {J Cataract Refract Surg},
	volume = {46},
	number = {11},
	year = {2020},
	month = {2020 Nov},
	pages = {1495-1500},
	abstract = {PURPOSE: To quantify the resident learning curve for cataract surgery using operative time as an indicator of surgical competency, to identify the case threshold at which marginal additional educational benefit became equivocal, and to characterize heterogeneity in residents{\textquoteright} pathways to surgical competency. SETTING: Academic medical center. DESIGN: Large-scale retrospective consecutive case series. METHODS: All cataract surgery cases performed by resident physicians as primary surgeon at Massachusetts Eye and Ear from July 1, 2010, through June 30, 2015, were reviewed. Data were abstracted from Accreditation Council for Graduate Medical Education case logs and operative time measurements. A linear mixed-methods analysis was conducted to model changes in residents{\textquoteright} cataract surgery operative times as a function of sequential case number, with resident identity included as a random effect in the model to normalize between-resident variability. RESULTS: A total of 2096 cases were analyzed. A marked progressive decrease in operative time was noted for resident cases 1 to 39 (mean change -0.17 minutes per additional case, 95\% CI, -0.21 to -0.12; P \&lt; .001). A modest, steady reduction in operative time was subsequently noted for case numbers 40 to 149 (mean change -0.05 minutes per additional case, 95\% CI, -0.07 to -0.04; P \&lt; .001). No statistically significant improvement was found in operative times beyond the 150th case. CONCLUSIONS: Residents derived educational benefit from performing a greater number of cataract procedures than current minimum requirements. However, cases far in excess of this threshold might have diminishing educational return in residency. Educational resources currently used for these cases might be more appropriately devoted to other training priorities.},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000000298},
	author = {Liebman, Daniel L and McKay, Kenneth Matthew and Haviland, Miriam J and Moustafa, Giannis A and Borkar, Durga S and Kloek, Carolyn E}
}
@article {913491,
	title = {IGF-1 in retinopathy of prematurity, a CNS neurovascular disease.},
	journal = {Early Hum Dev},
	volume = {102},
	year = {2016},
	month = {2016 Nov},
	pages = {13-19},
	abstract = {The retina is part of the central nervous system and both the retina as well as the brain can suffer from severe damage after very preterm birth. Retinopathy of prematurity is one of the major causes of blindness in these children and brain neuronal impairments including cognitive defects, cerebral palsy and intraventricular hemorrhage (IVH) are also complications of very preterm birth. Insulin-like growth factor 1 (IGF-1) acts to promote proliferation, maturation, growth and survival of neural cells. Low levels of circulating IGF-1 are associated with ROP and defects in the IGF-1 gene are associated with CNS disorders including learning deficits and brain growth restriction. Treatment of preterm infants with recombinant IGF-1 may potentially prevent ROP and CNS disorders. This review compares the role of IGF-1 in ROP and CNS disorders. A recent phase 2 study showed a positive effect of IGF-1 on the severity of IVH but no effect on ROP. A phase 3 trial is planned.},
	issn = {1872-6232},
	doi = {10.1016/j.earlhumdev.2016.09.008},
	author = {Liegl, Raffael and L{\"o}fqvist, Chatarina and Hellstr{\"o}m, Ann and Smith, Lois E H}
}
@article {603921,
	title = {Long-term Natural History of Dry Eye Disease from the Patient{\textquoteright}s Perspective.},
	journal = {Ophthalmology},
	volume = {123},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {425-33},
	abstract = {PURPOSE: To describe the natural history of dry eye disease (DED), which chronically affects millions of people in the United States. DESIGN: This study is based on the Women{\textquoteright}s Health Study and Physicians{\textquoteright} Health Studies, and uses questionnaires and medical records. PARTICIPANTS: A total of 398 men and 386 women who reported a diagnosis of DED and responded to a questionnaire about change in disease since diagnosis. METHODS: Three subscales were developed using factor analysis of questionnaire responses: ocular surface symptoms, vision-related symptoms, and social impact. We examined correlates of worsening on each subscale, obtained medical records from a subset of 261 study participants, and examined changes in clinical signs of DED over time. MAIN OUTCOME MEASURES: Worsening in ocular surface symptoms, vision-related symptoms, and social impact plus clinical signs. RESULTS: The average duration of DED of 10.5 years (standard deviation, 9.5 years). Worsening was reported by 24\% for ocular surface symptoms, 29\% for vision-related symptoms, and 10\% for social impact. Factors associated with worsening on at least 2 of 3 subscales included a previous report of severe DED symptoms (odds ratio [OR], 2.17 for ocular surface symptoms; OR, 2.35 for vision-related symptoms), spending \&gt;$20 per month on DED treatments (OR, 1.80 for ocular surface symptoms; OR, 1.99 for vision-related symptoms), history of blepharitis or meibomian gland dysfunction (MGD) (OR, 1.57 for vision-related symptoms; OR, 2.12 for social impact), and use of systemic beta-blockers (OR, 1.62 for ocular surface symptoms; OR, 1.84 for vision-related symptoms; OR, 1.86 for the social impact of DED). Presence of corneal staining based on review of medical records was associated with use of level 2 or higher DED treatments (OR, 1.54; confidence interval [CI], 1.01-2.36), a previous report of severe DED symptoms (OR, 1.79; CI, 1.07-3.00), having a tear break-up test performed (OR, 2.73; CI, 1.72-4.36), and having blepharitis or MGD (OR, 0.59; CI, 0.35-0.98). CONCLUSIONS: A proportion of patients with DED experience worsening over time, tending to report with more severe symptoms earlier in the disease. Forthcoming data on the natural history of DED from prospective studies should help clarify some of the limitations of this retrospective study.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.10.011},
	author = {Lienert, Jeffrey P and Tarko, Laura and Uchino, Miki and Christen, William G and Schaumberg, Debra A}
}
@article {341681,
	title = {Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy.},
	journal = {Br J Ophthalmol},
	volume = {99},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {837-41},
	abstract = {BACKGROUND: To investigate possible associations between diabetic retinopathy (DR) and systemic vascular endothelial function and arterial stiffness measured using reactive hyperaemia peripheral arterial tonometry. METHODS: This was a cross-sectional observational clinical study. Subjects with diabetes were recruited and DR was graded from retinal photographs. Systemic endothelial function was measured using reactive hyperaemia peripheral arterial tonometry (EndoPAT) and expressed as the reactive hyperaemia index (RHI). Peripheral arterial stiffness was measured using the same device and expressed as the augmentation index (AI). RESULTS: In total, 164 eyes of 95 Chinese patients were evaluated. The mean age of the subject eyes was 60.1{\textpm}8.2 years and 76.8\% were men. The mean duration of diabetes was 15.5{\textpm}9.8 years, and the mean HbA1c was 8.1{\textpm}1.4\%. In age-gender-adjusted models, increasing severity of DR was associated with increasing mean RHI (p=0.001) and increasing mean AI (p\&lt;0.001). In multivariate models, adjusting additionally for smoking, mean duration of diabetes, HbA1c and hypertension, the associations with RHI and AI persisted (p=0.011 and 0.001, respectively). In analyses of the dichotomous outcomes clinically significant macular oedema (CSME), moderate DR and vision-threatening DR, AI was a significant predictor of CSME and vision-threatening DR. In multivariate-adjusted models, for every SD increase in AI, the odds of having CSME was 1.78 times higher (95\% CI 1.05 to 2.99; p=0.029). For every SD increase in AI, the odds of having vision-threatening DR was 1.73 times higher (95\% CI 1.17 to 2.56; p=0.003). CONCLUSIONS: Subjects with more severe DR have larger peripheral reactive hyperaemic responses and greater peripheral vascular stiffness. These findings support the link between the microvascular changes of diabetes and macrovascular disease.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-306075},
	author = {Lim, Laurence S and Ling, Lieng H and Cheung, Chui Ming Gemmy and Ong, Peng Guan and Gong, Lingli and Tai, E Shyong and Mathur, Ranjana and Wong, Doric and Foulds, Wallace and Wong, Tien Yin}
}
@article {504056,
	title = {Prognostic factor analysis of vitrectomy for myopic foveoschisis.},
	journal = {Br J Ophthalmol},
	volume = {99},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {1639-43},
	abstract = {PURPOSE: To describe the anatomical and functional outcomes in a cohort of subjects undergoing vitrectomy for myopic foveoschisis, and to analyse the factors predicting foveal reattachment and visual improvement. METHODS: This retrospective case series evaluated case records and optical coherence tomography images 6 months after surgery. Multivariate linear and logistic regressions were performed to assess the factors predicting anatomical and visual improvement. RESULTS: In total, 55 eyes of 54 patients were analysed. The mean spherical equivalent refraction was -11.83{\textpm}4.94D. Foveal detachment was present in 63.5\% of eyes preoperatively and subjects with foveal detachment had 0.70 logMAR units (95\% CI 0.02 to 1.39) poorer visual acuity than subjects without (p=0.046). The mean preoperative visual acuity was 0.84{\textpm}0.59 logMAR units and the mean postoperative visual acuity was 0.64{\textpm}0.64 logMAR units (mean difference 0.20{\textpm}0.68 logMAR units (p=0.04)). The proportion of eyes with foveal detachment was significantly lower after surgery (12.5\%; p\&lt;0.001). However, the proportion of eyes with ellipsoid zone disruption was significantly higher after surgery (59.6\% vs 34.0\%; p\&lt;0.001). In multivariate analyses, the preoperative central foveal thickness significantly predicted postoperative visual improvement by two or more lines (OR 1.004 (95\% CI 1.000 to 1.007), per μm increase; p=0.049). The presence of ellipsoid zone disruption preoperatively was associated with 0.96 logMAR (95\% CI 0.2 to 1.72) poorer final acuity (p=0.02). CONCLUSIONS: Eyes with myopic foveoschisis with preoperative ellipsoid disruption and thinner central foveal thickness tend to have poorer visual outcomes. While current surgical manoeuvres are effective in reattaching the fovea, they may also cause iatrogenic injury to the photoreceptors.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-306885},
	author = {Lim, Laurence Shen and Ng, Wei Yan and Wong, Doric and Wong, Edmund and Yeo, Ian and Ang, Chong Lye and Kim, Leo and Vavvas, Demetrios and Lee, Shu Yen}
}
@article {1688256,
	title = {Causes of Childhood Blindness in the United States using the IRIS{\textregistered} Registry (Intelligent Research in Sight)},
	journal = {Ophthalmology},
	year = {2023},
	month = {2023 Apr 08},
	abstract = {PURPOSE: To investigate causes of childhood blindness in the United States using the IRIS{\textregistered} Registry (Intelligent Research in Sight). DESIGN: Cross-Sectional Study. PARTICIPANTS: Patients <=18 years of age with visual acuity 20/200 or worse in their better seeing eye in the IRIS Registry during 2018. METHODS: Causes of blindness were classified by anatomical site and specific diagnoses. MAIN OUTCOME MEASURES: Percentages of causes of blindness. RESULTS: Of 81,164 children with 2018 visual acuity data in the IRIS Registry, 961 (1.18\%) had visual acuity 20/200 or worse in their better-seeing eye. Leading causes of blindness were retinopathy of prematurity (ROP) in 301 (31.3\%), nystagmus in 78 (8.1\%), and cataract in 64 (6.7\%) patients. The retina was the leading anatomic site (47.7\%) followed by optic nerve (11.6\%) and lens (10.0\%). A total of 52.4\% of patients had treatable causes of blindness. CONCLUSIONS: This analysis offers a unique cross-sectional view of childhood blindness in the US using a clinical data registry. More than one-half of blind patients had a treatable cause of blindness.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.04.004},
	author = {Lim, Han Woong and Pershing, Suzann and Moshfeghi, Darius M and Heo, Hwan and Haque, Md Enamul and Lambert, Scott R and IRIS{\textregistered} Registry Analytic Center Consortium}
}
@article {1798481,
	title = {A Deep Learning Model for Screening Computed Tomography Imaging for Thyroid Eye Disease and Compressive Optic Neuropathy},
	journal = {Ophthalmol Sci},
	volume = {4},
	number = {1},
	year = {2024},
	month = {2024 Jan-Feb},
	pages = {100412},
	abstract = {PURPOSE: Thyroid eye disease (TED) is an autoimmune condition with an array of clinical manifestations, which can be complicated by compressive optic neuropathy. It is important to identify patients with TED early to ensure close monitoring and treatment to prevent potential permanent disability or vision loss. Deep learning artificial intelligence (AI) algorithms have been utilized in ophthalmology and in other fields of medicine to detect disease. This study aims to introduce a deep learning model to evaluate orbital computed tomography (CT) images for the presence of TED and potential compressive optic neuropathy.

DESIGN: Retrospective review and deep learning algorithm modeling.

SUBJECTS: Patients with TED with dedicated orbital CT scans and with an examination by an oculoplastic surgeon over a 10-year period at a single academic institution. Patients with no TED and normal CTs were used as normal controls. Those with other diagnoses, such as tumors or other inflammatory processes, were excluded.

METHODS: Orbital CTs were preprocessed and adopted for the Visual Geometry Group-16 network to distinguish patients with no TED, mild TED, and severe TED with compressive optic neuropathy. The primary model included training and testing of all 3 conditions. Binary model performance was also evaluated. An oculoplastic surgeon was also similarly tested with single and serial images for comparison.

MAIN OUTCOME MEASURES: Accuracy of deep learning model discernment of region of interest for CT scans to distinguish TED versus normal control, as well as TED with clinical signs of optic neuropathy.

RESULTS: A total of 1187 photos from 141 patients were used to develop the AI model. The primary model trained on patients with no TED, mild TED, and severe TED had 89.5\% accuracy (area under the curve: range, 0.96-0.99) in distinguishing patients with these clinical categories. In comparison, testing of an oculoplastic surgeon in these 3 categories showed decreased accuracy (70.0\% accuracy in serial image testing).

CONCLUSIONS: The deep learning model developed in the study can accurately detect TED and further detect TED with clinical signs of optic neuropathy based on orbital CT. The model proved superior compared with human expert grading. With further optimization and validation, this TED deep learning model could help guide frontline health care providers in the detection of TED and help stratify the urgency of a referral to an oculoplastic surgeon and endocrinologist.

FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100412},
	author = {Lin, Lisa Y and Zhou, Paul and Shi, Min and Lu, Jonathan E and Jeon, Soomin and Kim, Doyun and Liu, Josephine M and Wang, Mengyu and Do, Synho and Lee, Nahyoung Grace}
}
@article {1430531,
	title = {Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma},
	journal = {J Glaucoma},
	volume = {28},
	number = {5},
	year = {2019},
	month = {2019 May},
	pages = {473-480},
	abstract = {PR{\'e}CIS:: This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure (IOP) to a greater degree in angle-closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma. PURPOSE: Endocyclophotocoagulation (ECP) laser treatment of the ciliary processes is believed to decrease IOP by reducing aqueous production. Anecdotal experience in angle-closure glaucoma suggests that it may also lower IOP by opening the drainage angle to promote aqueous outflow. This study sought to evaluate combined phacoemulsification and ECP (phaco/ECP) in eyes with different types and stages of glaucoma. PATIENTS AND METHODS: A Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution was conducted. RESULTS: In 63 eyes of 63 patients with an average of 3.0{\textpm}1.7 years of follow-up, the 22 eyes with chronic angle-closure glaucoma (CACG) had greater IOP reduction and medication reduction than the 41 eyes with primary open-angle glaucoma at both 1 year (6.4 vs. 2.1 mm Hg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4 mm Hg, P=0.02; 0.9 vs. 0.3 medications, P=0.05). There was no difference in IOP reduction or medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11; 0.1, 0.8, 0.4 medications, P=0.14). CONCLUSIONS: Eyes with CACG were more responsive to phaco/ECP in terms of IOP and medication reduction compared with eyes with primary open-angle glaucoma. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Phaco/ECP was effective in all stages of glaucoma.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001225},
	author = {Lin, Michael M and Rageh, Abdulrahman and Turalba, Angela V and Lee, Hang and Falkenstein, Iryna A and Hoguet, Ambika S and Ojha, Pallavi and Rao, Veena S and Ratanawongphaibul, Kitiya and Rhee, Douglas J and Shen, Lucy Q and Song, Brian J and Chen, Teresa C}
}
@article {1761906,
	title = {ENDOGENOUS ENDOPHTHALMITIS DUE TO STREPTOCOCCUS ANGINOSUS IN A HEALTHY, YOUNG WOMAN},
	journal = {Retin Cases Brief Rep},
	volume = {17},
	number = {5},
	year = {2023},
	month = {2023 Sep 01},
	pages = {524-527},
	abstract = {PURPOSE: The purpose of this study was to present a case of indolent endogenous endophthalmitis in a young, seemingly healthy woman. METHODS: This study is a retrospective case report. RESULTS: A 25-year-old woman with no significant medical history presented with vision loss in the left eye over the course of 1 month. Examination showed vitritis and a white-yellow lesion overlying the macula and optic nerve in the left eye. Initial laboratory testing for infectious and inflammatory causes was unrevealing. A diagnostic vitrectomy was performed, and the patient was found to have presumed endogenous endophthalmitis due to Streptococcus anginosus, an extremely uncommon bacterium. Subsequent workup did not reveal evidence of bacteremia, endocarditis, or orbital infection. This case is unique because, unlike the three previously reported cases of S. anginosus endophthalmitis, this patient was seemingly healthy, never had an elevated white blood cell count, never had documented bacteremia, had a normal echocardiogram, and had normal orbital findings on magnetic resonance imaging and computed tomography scans. Further questioning revealed a remote history of facial cellulitis and possible sinusitis treated with oral antibiotics, which are the presumed etiology. CONCLUSION: Streptococcus anginosus endophthalmitis can occur in young, seemingly healthy patients. Endogenous endophthalmitis should be considered in the differential diagnosis even without systemic comorbidities or other risk factors. Detailed questioning about medical history and thorough review of systems, including nonocular symptoms, are essential.},
	keywords = {Adult, Bacteremia, Endophthalmitis, Female, Humans, Macula Lutea, Retrospective Studies, Streptococcus anginosus},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001245},
	author = {Lin, Jonathan B and Eliott, Dean and Sobrin, Lucia and Stryjewski, Tomasz P}
}
@article {1016101,
	title = {The relation between exercise and glaucoma in a South Korean population-based sample},
	journal = {PLoS One},
	volume = {12},
	number = {2},
	year = {2017},
	month = {2017},
	pages = {e0171441},
	abstract = {PURPOSE: To investigate the association between exercise and glaucoma in a South Korean population-based sample. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 11,246 subjects, 40 years and older who underwent health care assessment as part of the 2008-2011 Korean National Health and Nutrition Examination Survey. METHODS: Variables regarding the duration (total minutes per week), frequency (days per week), and intensity of exercise (vigorous, moderate exercise and walking) as well as glaucoma prevalence were ascertained for 11,246 survey participants. Demographic, comorbidity, and health-related behavior information was obtained via interview. Multivariable logistic regression analyses were performed to determine the association between the exercise-related parameters and odds of a glaucoma diagnosis. MAIN OUTCOME MEASURE(S): Glaucoma defined by International Society for Geographical and Epidemiological Ophthalmology criteria. RESULTS: Overall, 336 (2.7\%) subjects met diagnostic criteria for glaucomatous disease. After adjustment for potential confounding variables, subjects engaged in vigorous exercise 7 days per week had higher odds of having glaucoma compared with those exercising 3 days per week (Odds Ratio [OR] 3.33, 95\% confidence interval [CI] 1.16-9.54). High intensity of exercise, as categorized by the guidelines of the American College of Sports Medicine (ACSM), was also associated with greater glaucoma prevalence compared with moderate intensity of exercise (OR 1.55, 95\% CI 1.03-2.33). There was no association between other exercise parameters including frequency of moderate exercise, walking, muscle strength exercise, flexibility training, or total minutes of exercise per week, and the prevalence of glaucoma. In sub-analyses stratifying by gender, the association between frequency of vigorous exercise 7 days per week and glaucoma diagnosis remained significant in men (OR 6.05, 95\% CI 1.67-21.94) but not in women (OR 0.96 95\% CI: 0.23-3.97). A U-shaped association between exercise intensity and glaucoma prevalence was noted in men (OR 1.71, 95\% CI 1.09-2.69 for low intensity versus moderate intensity; OR 2.19, 95\% CI 1.25-3.85 for high intensity versus moderate intensity). CONCLUSION: In a South Korean population sample, daily vigorous exercise was associated with higher glaucoma prevalence. In addition, the intensity of exercise was positively associated with glaucoma diagnosis in men but not women.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0171441},
	author = {Lin, Shuai-Chun and Wang, Sophia Y and Pasquale, Louis R and Singh, Kuldev and Lin, Shan C}
}
@article {1806571,
	title = {Antisynthetase Syndrome Causing Necrotizing Myositis Involving Extraocular Muscles},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2024},
	month = {2024 Feb 09},
	abstract = {The authors describe the clinical, histologic, and serologic findings of a patient with necrotizing myositis of the extraocular muscles in the setting of antisynthetase syndrome, as well as subsequent management. This is the first case in the literature of a systemic necrotizing myositis to have associated ophthalmic findings.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002628},
	author = {Lin, Lisa Y and Azad, Amee D and Chiou, Carolina A and Kozanno, Liana and Stemmer-Rachamimov, Anat and Stone, John and Lee, Nahyoung Grace}
}
@article {1304385,
	title = {Characteristics and Visual Outcome of Refractory Retinal Vasculitis Associated With Antineutrophil Cytoplasm Antibody-Associated Vasculitides},
	journal = {Am J Ophthalmol},
	volume = {187},
	year = {2018},
	month = {2018 Mar},
	pages = {21-33},
	abstract = {PURPOSE: To describe the clinical characteristics, therapies, visual outcomes, and prognoses of patients with retinal vasculitis associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). DESIGN: Retrospective case series. METHODS: Patients diagnosed with retinal vasculitis associated with AAV and at least 6\&nbsp;months of follow-up were included. Demographic data, systemic and ocular features, best-corrected visual acuity at the initial visit and latest visit, fluorescein angiography (FA) and indocyanine green angiography (ICGA) findings, therapy regimen, and outcome were collected from the Massachusetts Eye Research and Surgery Institution (MERSI) database from 2006 to 2017. RESULTS: Fourteen patients (22 eyes) were identified. Twelve had granulomatosis with polyangiitis (GPA) and 1 each had microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). FA showed that AAV affected small-to-medium-size retinal vessels. Seven cases (50\%) had both vein/venule and artery/arteriole involvement. Four cases co-presented with choroidal vasculitis. All of them failed various immunomodulatory therapies prior to referral to MERSI. Six patients received rituximab plus prednisone as their final therapy and 5 of them achieved remission. Four patients who failed cyclophosphamide previously were induced into remission by rituximab. Patients were followed for 33.4 {\textpm} 25.5 (range 6-84) months. Nine of 14 patients (64.3\%) achieved remission at their latest visit. Seventeen of 22 eyes (77.3\%) met the criteria for a good (>=20/40) visual outcome. CONCLUSION: The majority of patients enjoyed a good visual outcome and achieved remission after aggressive treatment. Rituximab should be considered as an initial treatment for patients with refractory retinal vasculitis associated with AAV.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.12.004},
	author = {Lin, Miaoli and Anesi, Stephen D and Ma, Lina and Ahmed, Aseef and Small, Karen and Foster, C Stephen}
}
@article {1642387,
	title = {Femtosecond Laser-Assisted Cataract Surgery: A Report by the American Academy of Ophthalmology},
	journal = {Opthalmology},
	year = {2022},
	author = {CC Lin and Rose-Nussbaumer, JR and Al-Mohtaseb, ZN and Pantanelli, SM and Steigleman 3rd, WA and Hatch, K M and Santhiago, MR and Kim, S J and Schallhorn, JM}
}
@article {1645471,
	title = {Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Systematic Review},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {2},
	year = {2022},
	month = {2022 Jun},
	abstract = {Topic: To evaluate whether differences exist in systemic complement activation profiles in patients with early to intermediate nonexudative age-related macular degeneration (AMD) or geographic atrophy (GA) compared with control participants without AMD. Clinical Relevance: Complement inhibition has emerged as a therapeutic strategy for GA, although clinical trials to date have yielded mixed results. Despite these efforts, no clear consensus exists regarding what portions of the complement pathway are dysregulated in AMD or when this dysregulation occurs relative to AMD stage. Although past studies have compared systemic complement activation profiles in patients with AMD versus in control participants without AMD, differences in AMD case definition and differing analytical approaches complicate their interpretation. Methods: We performed a systematic review by identifying articles from database inception through October 11, 2020, that reported systemic complement activation profiles in patients with early or intermediate nonexudative AMD or GA versus control participants without AMD by searching PubMed, Google Scholar, and Embase. Risk of bias was assessed using a modified Newcastle-Ottawa score. Results: The 8 reviewed studies included 2131 independent participants. Most studies report significantly higher systemic levels of products associated with complement activation and significantly lower systemic levels of products associated with complement inhibition in patients with early and advanced nonexudative AMD compared with control participants without AMD. Discussion: Evidence suggests that systemic complement overactivation is a feature of early or intermediate and advanced nonexudative AMD. However, given significant heterogeneity, these findings are not conclusive and warrant further investigation.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100118},
	author = {Lin, Jonathan B and Stylianos Serghiou and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1466894,
	title = {In Reply: Protocol For Titrated Endocycloplasty When Combined With Phacoemulsification in an Exclusive Cohort of Angle Closure Glaucoma},
	journal = {J Glaucoma},
	volume = {28},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {e178-e179},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001376},
	author = {Lin, Michael M and Rageh, Abdulrahman and Turalba, Angela V and Lee, Hang and Falkenstein, Iryna A and Hoguet, Ambika S and Ojha, Pallavi and Rao, Veena S and Ratanawongphaibul, Kitiya and Rhee, Douglas J and Shen, Lucy Q and Song, Brian J and Chen, Teresa C}
}
@article {1732536,
	title = {Minocycline-induced Conjunctival Hyperpigmentation},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {4},
	year = {2023},
	month = {2023 Jul-Aug 01},
	pages = {e133},
	keywords = {Anti-Bacterial Agents, Conjunctiva, Humans, Hyperpigmentation, Minocycline},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002278},
	author = {Lin, Lisa Y and Stagner, Anna M and Freitag, Suzanne K}
}
@article {1661607,
	title = {Neuroprotection for Age-Related Macular Degeneration},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {4},
	year = {2022},
	month = {2022 Dec},
	pages = {100192},
	abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early to intermediate AMD is characterized by the accumulation of lipid- and protein-rich drusen. Late stages of the disease are characterized by the development of choroidal neovascularization, termed "exudative" or "neovascular AMD," or retinal pigment epithelium (RPE) cell and photoreceptor death, termed "geographic atrophy" (GA) in advanced nonexudative AMD. Although we have effective treatments for exudative AMD in the form of anti-VEGF agents, they have no role for patients with GA. Neuroprotection strategies have emerged as a possible way to slow photoreceptor degeneration and vision loss in patients with GA. These approaches include reduction of oxidative stress, modulation of the visual cycle, reduction of toxic molecules, inhibition of pathologic protein activity, prevention of cellular apoptosis or programmed necrosis (necroptosis), inhibition of inflammation, direct activation of neurotrophic factors, delivery of umbilical tissue-derived cells, and RPE replacement. Despite active investigation in this area and significant promise based on preclinical studies, many clinical studies have not yielded successful results. We discuss selected past and current neuroprotection trials for AMD, highlight the lessons learned from these past studies, and discuss our perspective regarding remaining questions that must be answered before neuroprotection can be successfully applied in the field of AMD research.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100192},
	author = {Lin, Jonathan B and Murakami, Yusuke and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1653609,
	title = {Clear Cell Syringoma of the Eyelids, a Distinctive Histopathologic Variant Associated with Diabetes Mellitus},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {1},
	year = {2023},
	month = {2023 Jan-Feb 01},
	pages = {e20-e22},
	abstract = {The authors describe the clinical and histologic findings of the clear cell variant of syringoma. Three adult female patients (age range 39-76 years old) were found to have multiple, flesh-colored lower eyelid papules, clinically consistent with syringomas, but histologically displaying abundant clear cell change. Two patients had known diagnoses of uncontrolled diabetes.},
	keywords = {Adult, Aged, Diabetes Mellitus, Eyelids, Female, Humans, Middle Aged, Sweat Gland Neoplasms, Syringoma},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002254},
	author = {Lin, Lisa Y and Lee, Nahyoung Grace and Yoon, Michael K and Stagner, Anna M}
}
@article {1653574,
	title = {Ocular Findings in Children with Headache},
	journal = {Ophthalmic Epidemiol},
	volume = {30},
	number = {4},
	year = {2023},
	month = {2023 Aug},
	pages = {392-399},
	abstract = {PURPOSE: To determine the prevalence of ophthalmological findings suggesting an ocular cause for headache or occult neurological disease, among children with headache. METHODS: Retrospective cross-sectional study on children with headache at a tertiary outpatient ophthalmology clinic. All children underwent sensorimotor, anterior segment, and dilated fundoscopic examinations, with or without cycloplegic refraction. Prevalence of one or more new findings of ocular or occult neurological cause of headache, including glaucoma, uveitis, optic nerve elevation, or possible asthenopia from strabismus or refractive issues. Headache characteristics and associated symptoms were evaluated as risk factors for ocular findings. RESULTS: Among 1,878 children with headache (mean age 10\&nbsp;yrs, range 2-18), 492 (26.1\%, 95\% CI 24.3-28.2\%) children had one or more new ocular findings that could cause headache or indicate intracranial disease: refractive issues (342, 18.2\%), strabismus (83, 4.4\%), optic nerve elevation (51, 2.7\%; 26 with papilledema, 25 with pseudopapilledema), uveitis (6, 0.3\%), and glaucoma (2, 0.1\%). Shorter headache duration was associated with ocular findings (p\&nbsp;=\&nbsp;.047), but headache frequency, photophobia, nausea/vomiting, and visual changes were not. In univariable analysis, visual changes (p\&nbsp;<=\&nbsp;.001), nausea/vomiting (p\&nbsp;<=\&nbsp;.002), and morning headache (p\&nbsp;=\&nbsp;.02) were associated with optic nerve elevation. CONCLUSION: An ophthalmologic examination including cycloplegic refraction is indicated in children with headache, as one-quarter have a treatable ocular condition, which may be related to the headache, or sign of intracranial pathology. While nausea, visual changes, or morning headache should raise concern, coincident visual, ocular, or systemic symptoms are not reliable predictors of discovering ocular pathology in a child with headache.},
	keywords = {Adolescent, Child, Child, Preschool, Cross-Sectional Studies, Glaucoma, Headache, Humans, Mydriatics, Refraction, Ocular, Retrospective Studies, Strabismus},
	issn = {1744-5086},
	doi = {10.1080/09286586.2022.2125019},
	author = {Lin, Lisa Y and Pan, Wei and Ying, Gui-Shuang and Binenbaum, Gil}
}
@article {1814316,
	title = {Retinal detachment},
	journal = {Nat Rev Dis Primers},
	volume = {10},
	number = {1},
	year = {2024},
	month = {2024 Mar 14},
	pages = {18},
	abstract = {Retinal detachment (RD) occurs when the neurosensory retina, the neurovascular tissue responsible for phototransduction, is separated from the underlying retinal pigment epithelium (RPE). Given the importance of the RPE for optimal retinal function, RD invariably leads to decreased vision. There are three main types of RD: rhegmatogenous, tractional and exudative (also termed serous) RD. In rhegmatogenous RD, one or more retinal breaks enable vitreous fluid to enter the subretinal space and separate the neurosensory retina from the RPE. In tractional RD, preretinal, intraretinal or subretinal membranes contract and exert tangential forces and elevate the retina from the underlying RPE. Finally, in exudative RD, an underlying inflammatory condition, vascular abnormality or the presence of a tumour causes exudative fluid to accumulate in the subretinal space, exceeding the osmotic pump function of the RPE. The surgical management of RD usually involves pars plana vitrectomy, scleral buckling or pneumatic retinopexy. The approach taken often depends on patient characteristics as well as on practitioner experience and clinical judgement. Advances in surgical technology and continued innovation have improved outcomes for many patients. However, even if retinal re-attachment is achieved, some patients still experience decreased vision or other visual symptoms, such as metamorphopsia, that diminish their quality of life. Continued research in the areas of neuroprotection and retinal biology as well as continued surgical innovation are necessary to enhance therapeutic options and outcomes for these patients.},
	keywords = {Humans, Quality of Life, Retinal Detachment, Scleral Buckling, Treatment Outcome, Vitrectomy},
	issn = {2056-676X},
	doi = {10.1038/s41572-024-00501-5},
	author = {Lin, Jonathan B and Narayanan, Raja and Philippakis, Elise and Yonekawa, Yoshihiro and Apte, Rajendra S}
}
@article {1629453,
	title = {Dyslipidemia in age-related macular degeneration},
	journal = {Eye (Lond)},
	volume = {36},
	number = {2},
	year = {2022},
	month = {2022 Feb},
	pages = {312-318},
	abstract = {Lipid-rich drusen are the sine qua non of age-related macular degeneration (AMD), the leading cause of blindness in older adults in the developed world. Efforts directed at uncovering effective therapeutic strategies have led to the hypothesis that altered lipid metabolism may play a pathogenic role in AMD. This hypothesis is supported by the fact that: (1) drusen, the hallmark histopathologic feature of AMD, are composed of lipids, (2) polymorphisms of genes involved in lipid homeostasis are associated with increased odds of AMD, (3) metabolomics studies show that patients with AMD have alterations in metabolites from lipid pathways, and (4) alterations in serum lipid profiles as a reflection of systemic dyslipidemia are associated with AMD. There is strong evidence that statins, which are well described for treating dyslipidemia and reducing risk associated with cardiovascular disease, may have a role for treating certain cohorts of AMD patients, but this has yet to be conclusively proven. Of interest, the specific changes in serum lipoprotein profiles associated with decreased cardiovascular risk (i.e., high HDL levels) have been shown in some studies to be associated with increased risk of AMD. In this review, we highlight the evidence that supports a role for altered lipid metabolism in AMD and provide our perspective regarding the remaining questions that need to be addressed before lipid-based therapies can emerge for specific cohorts of AMD patients.},
	issn = {1476-5454},
	doi = {10.1038/s41433-021-01780-y},
	author = {Lin, Jonathan B and Halawa, Omar A and Husain, Deeba and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1638576,
	title = {Posterior Ischemic Optic Neuropathy in the Setting of Cocaine-Induced Orbital and Sinonasal Inflammation},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {5},
	year = {2022},
	month = {2022 Sep-Oct 01},
	pages = {e141-e144},
	abstract = {Intranasal cocaine abuse can lead to significant sinus and orbital complications, including optic neuropathy. A 46-year-old man with a history of recurrent cocaine-induced sino-orbital inflammation and infection with bony destruction presented with acute, painless, vision loss. Examination revealed no light perception vision. MRI of the orbits demonstrated new restricted diffusion of the right optic nerve on diffusion-weighted imaging and apparent diffusion coefficient sequences, consistent with posterior ischemic optic neuropathy. This is the first among cases of cocaine-induced optic neuropathy in the literature to illustrate ischemic changes on MRI in the optic nerve, highlighting the utility of diffusion-weighted imaging/apparent diffusion coefficient sequences when optic neuropathy is suspected and further suggesting an underlying ischemic etiology in similar cases.},
	keywords = {Cocaine, Humans, Inflammation, Male, Middle Aged, Optic Nerve, Optic Nerve Diseases, Optic Neuropathy, Ischemic},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002181},
	author = {Lin, Lisa Y and Reshef, Edith R and Lansberg, Marianella Paz and Barshak, Miriam B and Chwalisz, Bart K and Holbrook, Eric H and Wolkow, Natalie}
}
@article {1732621,
	title = {Eosinophilic Angiocentric Fibrosis of the Orbit: A Clinicopathologic Review of 6 Novel Cases With Review of the Literature},
	journal = {Am J Ophthalmol},
	volume = {256},
	year = {2023},
	month = {2023 Dec},
	pages = {9-19},
	abstract = {PURPOSE: To describe 6 cases and review the current state of knowledge of eosinophilic angiocentric fibrosis (EAF) involving the orbit. DESIGN: Retrospective clinicopathologic case series and review of the current literature METHODS: Clinical records and histopathologic data of orbit-involving EAF were gathered between 2004 and 2022 from a single academic institution. The patients{\textquoteright} presenting clinical symptoms and signs, laboratory data, radiographic studies, and management documentation were collected. RESULTS: Retrospective review identified 6 novel cases, totaling 31 cases of EAF involving the orbit described as of this writing. Fourteen patients were male, and the average age of presentation was 49.8 years (range 25-78 years). Eighteen patients had concurrent sinonasal involvement, whereas 13 had primary orbital involvement. The median duration of symptoms prior to evaluation was 24 months, with nasal symptoms, proptosis, periorbital swelling, and pain being the most common presenting symptoms. The majority of patients underwent surgical debulking, as well as treatment with glucocorticoids and steroid-sparing agents, such as rituximab, with varied results. CONCLUSION: EAF involving the orbit is uncommon. The histopathologic findings include a perivascular, eosinophil-rich infiltrate and a pauci-inflammatory storiform type of fibrosis concentrated around small vessels. Orbital involvement usually results from local extension from adjacent sinuses, but primary orbital involvement has been described. Surgical debulking and immunosuppressive agents such as rituximab have been shown to stabilize disease.},
	keywords = {Adult, Aged, Eosinophilia, Female, Fibrosis, Humans, Male, Middle Aged, Orbit, Retrospective Studies, Rituximab},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.07.016},
	author = {Lin, Lisa Y and Stone, John H and Liou, Victor D and Stagner, Anna M and Lee, N Grace}
}
@article {1748421,
	title = {Neurofilament Light Chain in Aqueous Humor as a Marker of Neurodegeneration in Glaucoma},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {2209-2217},
	abstract = {PURPOSE: Neurofilament light chain (NfL) is a neuronal cytoskeletal protein that has been identified as a marker of neurodegeneration in diseases of the central nervous system. In this study, we investigated whether NfL in the aqueous humor (AH) can serve as a marker of neurodegeneration in glaucoma in a racially diverse North American population. DESIGN: Single-center, case-control study. PARTICIPANTS: We enrolled patients with various types and stages of glaucoma undergoing planned ophthalmic surgery as part of their routine care and compared them with patients without glaucoma undergoing phacoemulsification for age-related cataract. METHODS: We collected AH from 39 glaucoma patients and 10 patients without glaucoma. AH NfL was quantified using the Single-Molecule Array (Simoa){\textregistered} NF-light assay (Quanterix). Demographic information, such as age, body mass index, sex, and self-reported race, as well as clinical information, such as pre-operative intraocular pressure (IOP), maximum IOP, and number of pre-operative glaucoma medications, was obtained by reviewing the medical record. MAIN OUTCOME MEASURES: Levels of AH NfL. RESULTS: In a model controlling for age and body mass index (BMI), NfL was significantly elevated in AH from glaucoma patients (mean: 429 pg/mL; standard deviation [SD]: 1136 pg/mL) compared to AH from patients without glaucoma (mean: 3.1 pg/mL; SD: 1.9 pg/mg): P = 0.002. Higher AH NfL was associated with higher maximum IOP (R = 0.44, P = 0.005), higher pre-operative IOP (R = 0.46, P = 0.003), and more pre-operative glaucoma medications (Rs = 0.61, P \&lt; 0.001). There was no association between AH NfL and Humphrey visual field mean deviation (R = -0.20, P = 0.220), retinal nerve fiber layer thickness as measured with optical coherence tomography (R = 0.07, P = 0.694), or glaucoma stage (Rs = 0.015, P = 0.935). CONCLUSION: Our findings suggest that AH NfL may have clinical utility as a marker of glaucomatous neurodegeneration.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S417664},
	author = {Lin, Jonathan B and Pitts, Kristen M and El Helwe, Hani and Neeson, Cameron and Hall, Nathan E and Falah, Henisk and Schultz, Stephanie A and Wang, Silas L and Lo, Kristine and Song, Christian and Margeta, Milica A and Sol{\'a}-Del Valle, David}
}
@article {1295871,
	title = {The Association Between Body Mass Index and Open-angle Glaucoma in a South Korean Population-based Sample},
	journal = {J Glaucoma},
	volume = {27},
	number = {3},
	year = {2018},
	month = {2018 Mar},
	pages = {239-245},
	abstract = {PURPOSE: The purpose of this article is to investigate the association between body mass index (BMI) and open-angle glaucoma (OAG) in a sample of the South Korean population. MATERIALS AND METHODS: The sample consisted of a cross-sectional, population-based sample of 10,978 participants, 40 years of age and older, enrolled in the 2008 to 2011 Korean National Health and Nutrition Examination Survey. All participants had measured intraocular pressure \&lt;22 mm Hg and open anterior chamber angles. OAG was defined using disc and visual field criteria established by the International Society for Geographical and Epidemiological Ophthalmology. Multivariable analyses were performed to determine the association between BMI and OAG. These analyses were also performed in a sex-stratified and age-stratified manner. RESULTS: After adjusting for potential confounding variables, lower BMI (\&lt;19 kg/m) was associated with greater risk of OAG compared with normal BMI (19 to 24.9 kg/m) [odds ratio (OR), 2.28; 95\% confidence interval (CI), 1.22-4.26]. In sex-stratified analyses, low BMI remained adversely related to glaucoma in women (OR, 3.45; 95\% CI, 1.42-8.38) but not in men (OR, 1.72; 95\% CI, 0.71-4.20). In age-stratified analyses, lower BMI was adversely related to glaucoma among subjects 40- to 49-year old (OR, 5.16; 95\% CI, 1.86-14.36) but differences in glaucoma prevalence were not statistically significant between those with low versus normal BMI in other age strata. CONCLUSIONS: Lower BMI was associated with increased odds of OAG in a sample of the South Korean population. Multivariate analysis revealed the association to be statistically significant in women and those in the youngest age stratum.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000867},
	author = {Lin, Shuai-Chun and Pasquale, Louis R and Singh, Kuldev and Lin, Shan C}
}
@article {1424808,
	title = {Recurrent corneal erosion syndrome},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {1204-1208},
	abstract = {Recurrent corneal erosion syndrome (RCES) is a disorder characterised by a dysfunctional epithelial ecosystem. It often begins after trauma, or in the setting of epithelial basement membrane degeneration or dystrophy. Historically, RCES has been understood as a structural derangement of the anterior corneal architecture. More recently, studies have demonstrated the important role of neuropeptides in corneal homoeostasis. Thus, RCES may also be understood as a disorder of corneal epithelial cell biology. Management of RCES can be challenging, but newer therapies have demonstrated improved efficacy for this condition. This review examines the aetiology and pathogenesis of RCES, and provides an update on current and emerging treatment modalities for the management of this disorder.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-313835},
	author = {Lin, Shawn Rong and Aldave, Anthony J and Chodosh, James}
}
@article {1559538,
	title = {Seeing Parkinson Disease in the Retina},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {2},
	year = {2021},
	month = {2021 Feb 01},
	pages = {189-190},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.5719},
	author = {Lin, Jonathan B and Apte, Rajendra S}
}
@article {1586138,
	title = {Refusal rates and waivers of informed consent in pragmatic and comparative effectiveness RCTs: A systematic review},
	journal = {Contemp Clin Trials},
	volume = {104},
	year = {2021},
	month = {2021 Mar 15},
	pages = {106361},
	abstract = {BACKGROUND: Pragmatic and comparative effectiveness randomized controlled trials (RCTs) aim to be highly generalizable studies, with broad applicability and flexibility in methods. These trials also address recruitment issues by minimizing exclusions. The trials may also appeal to potential subjects because of lower risk and lower burdens of participation. We sought to examine rates of refusal and uses of waivers of informed consent in pragmatic and comparative effectiveness RCTs. METHODS: A systematic review of pragmatic and comparative effectiveness RCTs performed wholely or in part in the United States and first published in 2014 and 2017. RESULTS: 103 studies involving 105 discrete populations were included for review. Refusal data was collected for 71 RCTs. Overall, studies reported an average rate of 31.9\% of potential subjects refused participation; on an individual basis, 38.4\% of people asked to take part refused at some point during recruitment. 23 trials (22\%) were performed, at least in part, with a waiver of informed consent, 7 (30\%) of which provided any form of notice to subjects. CONCLUSIONS: Overall refusal rates for pragmatic and comparative effectiveness RCTs appear roughly the same as other types of research, with studies reporting about a third of people solicited for participation refuse. Moreover, informed consent was waived in 22\% (95\% Binomial exact Confidence Interval 13.9-30.5\%) of the trials, and further study is needed to understand when waivers are justified and when notice should be provided.},
	issn = {1559-2030},
	doi = {10.1016/j.cct.2021.106361},
	author = {Lin, Lisa Y and Jochym, Nicole and Merz, Jon F}
}
@article {313206,
	title = {Fingernail-induced corneal abrasions: case series from an ophthalmology emergency department},
	journal = {Cornea},
	volume = {33},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {691-5},
	abstract = {PURPOSE: Fingernail-induced corneal abrasions are one of the most common eye injuries that present to the emergency department, and yet there is little literature available to offer guidelines for management. We analyzed the treatment used in cases of fingernail-induced corneal abrasions that presented to the Massachusetts Eye and Ear Infirmary Emergency Department and studied its relationship to the development of complications such as recurrent erosion syndrome and infection. METHODS: We performed a retrospective review of 99 patients who presented to the Massachusetts Eye and Ear Infirmary Emergency Department with fingernail-induced corneal abrasions between January 1, 2009 and December 31, 2009. We followed the patients for 12 months and documented demographics, nature of the injury, treatment, and complications. RESULTS: The average age was 29.4 (range, 2-89) years. Forty-four percent (n = 44) were female and 56\% (n = 55) were male. Of the 99 subjects, 39 had a full 12 month follow-up, and 7 developed a complication from the injury. Compared with the 32 subjects without complications, there was no difference in age or gender. However, there was a significant difference in that adults scratched by another adult were more highly represented in the group with complications (43\%, n = 3/7 vs. 3\%, n = 1/32; P = 0.0017). There was no significant difference in outcome by treatment used. CONCLUSIONS: This is the largest fingernail-induced corneal abrasion study completed to date. Patients are at risk of developing complications, but there is scant evidenced-based literature available for treating this common injury. Prospective trials should be performed to better optimize and standardize treatments.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Corneal Injuries, Emergency Service, Hospital, Epithelium, Corneal, Eye Injuries, Female, Humans, Male, Massachusetts, Middle Aged, Nails, Ophthalmology, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000133},
	author = {Lin, Yijie B and Gardiner, Matthew F}
}
@article {1043246,
	title = {A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts},
	journal = {PLoS One},
	volume = {12},
	number = {3},
	year = {2017},
	month = {2017},
	pages = {e0173997},
	abstract = {The Nurses{\textquoteright} Health Study (NHS), Nurses{\textquoteright} Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (β = 0.45, p = 3.48x10-22), and using a significance level of p = 0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR = 2.17, 95\% CI: 1.79-2.63, p = 2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0173997},
	author = {Lindstr{\"o}m, Sara and Loomis, Stephanie and Turman, Constance and Huang, Hongyan and Huang, Jinyan and Aschard, Hugues and Chan, Andrew T and Choi, Hyon and Cornelis, Marilyn and Curhan, Gary and De Vivo, Immaculata and Eliassen, A Heather and Fuchs, Charles and Gaziano, Michael and Hankinson, Susan E and Hu, Frank and Jensen, Majken and Kang, Jae H and Kabrhel, Christopher and Liang, Liming and Pasquale, Louis R and Rimm, Eric and Stampfer, Meir J and Tamimi, Rulla M and Tworoger, Shelley S and Wiggs, Janey L and Hunter, David J and Kraft, Peter}
}
@article {1615229,
	title = {Comparative Incidence of Periocular Surgical Site Infections with Increased Surgical Mask Use during the COVID-19 Pandemic},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Sep 15},
	pages = {1-6},
	abstract = {PURPOSE: To evaluate the effect of surgical mask use on infection rates for office-based periocular surgeries during the pandemic. METHODS: An Institutional Review Board-approved retrospective review of medical records identified patients who had an office-based oculofacial plastic surgery procedure during the pandemic between March and December 2020. Statistical analysis was used to compare this group to patients that underwent procedures between March and December 2019, prior to the pandemic when neither surgeon nor patient wore a surgical mask. RESULTS: The study consisted of 680 patients. Thirty-one different types of procedures were encountered. The incidence of infections in 2020 compared to 2019 was not statistically significant (1.12\% (n =\&nbsp;3) versus 1.21\% (n =\&nbsp;5), p =\&nbsp;1). All patients with infections were treated with oral antibiotics and improved without long-term complications. CONCLUSIONS: Periocular surgical site infections are uncommon, and the wearing of surgical masks by patient and surgeon during our office-based oculofacial procedures did not change the incidence of SSIs.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2021.1974491},
	author = {Liou, Victor and Yoon, Michael}
}
@article {1522733,
	title = {Advances in steroid sparing medical management of active thyroid eye disease},
	journal = {Semin Ophthalmol},
	year = {2020},
	month = {2020 Jul 20},
	pages = {1-8},
	abstract = {Thyroid eye disease (TED) is an autoimmune inflammatory disease of the orbit and the most common extrathyroidal manifestation of Graves disease. The release of pro-inflammatory cytokines is associated with inflammation of the ocular surface and lacrimal gland along with periorbital skin erythema and edema. Resultant tissue remodeling, fibrosis, and fat deposition can impart permanent physical changes to the ocular adnexa with effects on function and cosmesis. These changes occur in the active phase of disease, and it is during this time that steroids are often relied on to help alleviate symptoms. Due to the common and predictable side effects of long-term and high-dose steroid use, there has been a continuous effort to find alternative steroid-sparing medical management options for TED. This review highlights the various research studies that support the use of these medications.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1791911},
	author = {Liou, Victor D and Yoon, Michael K}
}
@article {1629463,
	title = {Orbital Inflammation in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Report and Review of the Literature},
	journal = {J Neuroophthalmol},
	year = {2022},
	month = {2022 Jan 04},
	abstract = {BACKGROUND: To present 2 patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease with unilateral orbital inflammation, optic nerve head edema, and abnormalities of the optic nerve and nerve sheath on imaging. We review the most current literature on this important and uncommon clinical phenotype. METHODS: A case report of 2 patients and a comprehensive review of the relevant literature on orbital inflammation in MOG antibody-associated disease (MOG-AD). RESULTS: Two patients presented with decreased vision and unilateral orbital inflammation. Both had optic nerve head edema and abnormalities of the optic nerve and nerve sheath on imaging. The patients were treated with immunosuppressants and had improvement of vision changes as well as their orbital inflammatory signs. MOG antibody was positive in high titers in both patients. Only 3 other cases of orbital inflammation associated with MOG antibody have been described. In all cases, orbital signs responded rapidly to intravenous methylprednisolone, but the improvement in visual acuity was variable and less robust. CONCLUSION: Orbital inflammation is a unique and underrecognized phenotype of MOG-AD with only a few reports in the literature. In patients who present with vision loss and orbital inflammation, MOG-AD should be considered in the differential.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001400},
	author = {Liou, Victor D and Yoon, Michael K and Maher, Mary and Chwalisz, Bart K}
}
@article {1179146,
	title = {Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {11},
	year = {2017},
	month = {2017 Sep 01},
	pages = {4530-4544},
	abstract = {Purpose: Goblet cells in the conjunctiva secrete mucin into the tear film protecting the ocular surface. The proresolution mediator resolvin D1 (RvD1) regulates mucin secretion to maintain homeostasis during physiological conditions and in addition, actively terminates inflammation. We determined the signaling mechanisms used by RvD1 in cultured rat conjunctival goblet cells to increase intracellular [Ca2+] ([Ca2+]i) and induce glycoconjugate secretion. Methods: Increase in [Ca2+]i were measured using fura 2/AM and glycoconjugate secretion determined using an enzyme-linked lectin assay with the lectin Ulex Europaeus Agglutinin 1. Signaling pathways activated by RvD1 were studied after goblet cells were pretreated with signaling pathway inhibitors before stimulation with RvD1. The results were compared with results when goblet cells were stimulated with RvD1 alone and percent inhibition calculated. Results: The increase in [Ca2+]i stimulated by RvD1 was blocked by inhibitors to phospholipases (PL-) -D, -C, -A2, protein kinase C (PKC), extracellular signal-regulated kinases (ERK)1/2 and Ca2+/calmodulin-dependent kinase (Ca2+/CamK). Glycoconjugate secretion was significantly inhibited by PLD, -C, -A2, ERK1/2 and Ca2+/CamK, but not PKC. Conclusions: We conclude that RvD1 increases glycoconjugate secretion from goblet cells via multiple signaling pathways including PLC, PLD, and PLA2, as well as their signaling components ERK1/2 and Ca2+/CamK to preserve the mucous layer and maintain homeostasis by protecting the eye from desiccating stress, allergens, and pathogens.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-21914},
	author = {Lippestad, Marit and Hodges, Robin R and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1309948,
	title = {Signaling pathways activated by resolvin E1 to stimulate mucin secretion and increase intracellular Ca in cultured rat conjunctival goblet cells},
	journal = {Exp Eye Res},
	volume = {173},
	year = {2018},
	month = {2018 Aug},
	pages = {64-72},
	abstract = {Glycoconjugate mucin secretion from conjunctival goblet cells is tightly regulated by nerves and specialized pro-resolving mediators (SPMs) to maintain ocular surface health. Here we investigated the actions of the SPM resolvin E1 (RvE1) on cultured rat conjunctival goblet cell glycoconjugate secretion and intracellular [Ca] ([Ca]) and the signaling pathways used by RvE1. Goblet cells were cultured from rat conjunctiva in RPMI medium. The amount of RvE1-stimulated glycoconjugate mucin secretion was determined using an enzyme-linked lectin assay with Ulex Europaeus Agglutinin 1 lectin. Cultured goblet cells were also incubated with the Ca indicator dye fura 2/AM and [Ca] was measured. Cultured goblet cells were incubated with inhibitors to phospholipase (PL-) C, D, and A2 signaling pathways. RvE1 stimulated glycoconjugate secretion in a concentration dependent manner and was inhibited with the Ca chelator BAPTA. The Ca response was also increased in a concentration manner when stimulated by RvE1. Inhibition of PLC, PLD, and PLA2, but not Ca/calmodulin-dependent kinase blocked RvE1-stimulated increase in [Ca] and glycoconjugate secretion. We conclude that under normal, physiological conditions RvE1 stimulates multiple pathways to increase glycoconjugate secretion and [Ca]. RvE1 could be an important regulator of goblet cell glycoconjugate mucin secretion to maintain ocular surface health.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.04.015},
	author = {Lippestad, Marit and Hodges, Robin R and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1645469,
	title = {Evidence of beta amyloid independent small vessel disease in familial Alzheimer{\textquoteright}s disease},
	journal = {Brain Pathol},
	volume = {32},
	number = {6},
	year = {2022},
	month = {2022 Nov},
	pages = {e13097},
	abstract = {We studied small vessel disease (SVD) pathology in Familial Alzheimer{\textquoteright}s disease (FAD) subjects carrying the presenilin 1 (PSEN1) p.Glu280Ala mutation in comparison to those with sporadic Alzheimer{\textquoteright}s disease (SAD) as a positive control for Alzheimer{\textquoteright}s pathology and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) bearing different NOTCH3 mutations, as positive controls for SVD pathology. Upon magnetic resonance imaging (MRI) in life, some FAD showed mild white matter hyperintensities and no further radiologic evidence of SVD. In post-mortem studies, total SVD pathology in cortical areas and basal ganglia was similar in PSEN1 FAD and CADASIL subjects, except for the feature of arteriosclerosis which was higher in CADASIL subjects than in PSEN1 FAD subjects. Further only a few SAD subjects showed a similar degree of SVD pathology as observed in CADASIL. Furthermore, we found significantly enlarged perivascular spaces in vessels devoid of cerebral amyloid angiopathy in FAD compared with SAD and CADASIL subjects. As expected, there was greater fibrinogen-positive perivascular reactivity in CADASIL but similar reactivity in PSEN1 FAD and SAD groups. Fibrinogen immunoreactivity correlated with onset age in the PSEN1 FAD cases, suggesting increased vascular permeability may contribute to cognitive decline. Additionally, we found reduced perivascular expression of PDGFRβ AQP4 in microvessels with enlarged PVS in PSEN1 FAD cases. We demonstrate that there is Aβ-independent SVD pathology in PSEN1 FAD, that was marginally lower than that in CADASIL subjects although not evident by MRI. These observations suggest presence of covert SVD even in PSEN1, contributing to disease progression. As is the case in SAD, these consequences may be preventable by early recognition and actively controlling vascular disease risk, even in familial forms of dementia.},
	keywords = {Alzheimer Disease, Amyloid beta-Peptides, CADASIL, Fibrinogen, Flavin-Adenine Dinucleotide, Humans},
	issn = {1750-3639},
	doi = {10.1111/bpa.13097},
	author = {Littau, Jessica Lisa and Velilla, Lina and Hase, Yoshiki and Villalba-Moreno, Nelson David and Hagel, Christian and Drexler, Dagmar and Osorio Restrepo, Santiago and Villegas, Andres and Lopera, Francisco and Vargas, Sergio and Glatzel, Markus and Krasemann, Susanne and Quiroz, Yakeel T and Arboleda-Velasquez, Joseph F and Kalaria, Rajesh and Sepulveda-Falla, Diego}
}
@article {1287961,
	title = {The Effect of Solithromycin, a Cationic Amphiphilic Drug, on the Proliferation and Differentiation of Human Meibomian Gland Epithelial Cells},
	journal = {Curr Eye Res},
	volume = {43},
	number = {6},
	year = {2018},
	month = {2018 Jun},
	pages = {683-688},
	abstract = {PURPOSE: We previously discovered that azithromycin (AZM) acts directly on immortalized human meibomian gland epithelial cells (IHMGECs) to stimulate their lipid and lysosome accumulation and overall differentiation. We hypothesize that this phospholipidosis-like effect is due to AZM{\textquoteright}s cationic amphiphilic drug (CAD) nature. If our hypothesis is correct, then other CADs (e.g., solithromycin [SOL]) should be able to duplicate AZM{\textquoteright}s action on IHMGECs. Our purpose was to test this hypothesis.

MATERIALS AND METHODS: IHMGECs were cultured in the presence of vehicle or SOL (2, 10, or 20~{\textmu}g/ml) for up to 7~days under proliferating or differentiating conditions. Positive (epidermal growth factor and bovine pituitary extract for proliferation; AZM for differentiation) and negative (vehicle) controls were included with the experiments. IHMGECs were evaluated for cell number, neutral lipid content, and lysosome accumulation.

RESULTS: Our results demonstrate that SOL induces a rapid and dose-dependent increase in the accumulation of neutral lipids and lysosomes in HMGECs. The lysosomal effects were most prominent with the 10 and 20~{\textmu}g/ml doses, and occurred earlier (i.e., 1 day) with SOL than with the AZM (10~{\textmu}g/ml) control. The effects of SOL and AZM on IHMGEC differentiation were essentially the same after 3~days of culture. SOL did not influence the proliferation of HMGECs during a 7-day time period.

CONCLUSIONS: Our results support our hypothesis that SOL, a CAD, is able to reproduce AZM{\textquoteright}s impact on lysosome and lipid accumulation, as well as the differentiation, of HMGECs. The effect of SOL on lysosome appearance was faster than that of AZM.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2017.1418894},
	author = {Liu, Yang and Kam, Wendy R and Fernandes, Prabhavathi and Sullivan, David A}
}
@article {1125346,
	title = {Animal models of ocular angiogenesis: from development to pathologies},
	journal = {FASEB J},
	volume = {31},
	number = {11},
	year = {2017},
	month = {2017 Nov},
	pages = {4665-4681},
	abstract = {Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies.},
	keywords = {Animals, Choroidal Neovascularization, Diabetic Retinopathy, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Retinal Neovascularization},
	issn = {1530-6860},
	doi = {10.1096/fj.201700336R},
	author = {Liu, Chi-Hsiu and Wang, Zhongxiao and Sun, Ye and Chen, Jing}
}
@article {314156,
	title = {Comparison of intravitreal triamcinolone acetonide versus intravitreal bevacizumab as the primary treatment of clinically significant macular edema.},
	journal = {Retina},
	volume = {35},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {272-9},
	abstract = {OBJECTIVES: To evaluate the short-term efficacy of triamcinolone acetonide versus bevacizumab for the treatment of diabetic, clinically significant, macular edema with different optical coherence tomography findings. METHODS: Fifty eyes of 45 consecutive patients with diabetic, clinically significant, macular edema were incorporated in this prospective interventional case series. Patients were divided into 3 groups according to findings on optical coherence tomography: 1) macular edema combined with serous retinal detachment (Group 1), 2) diffused macular thickening (Group 2), and 3) cystoid macular edema (Group 3). Patients from each group were treated with a single intravitreal injection of triamcinolone (IVTA) or 2 intravitreal injections of bevacizumab (IVB) with an interval of 6 weeks. Patients were observed at 6, 12, and 24 weeks after IVTA or the first IVB injection. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were examined at each visit. Repeated-measures analysis of variance was used to compare the efficacy of the treatment groups. RESULTS: In Group 1, IVTA showed more favorable effects on CRT reduction and BCVA improvement compared with IVB at 6, 12, and 24 weeks (P = 0.002, 0.001, 0.027 and P = 0.036, 0.001, 0.027), respectively. In Group 2, IVB had more CRT reduction than IVTA at 6 and 12 weeks (P = 0.013 and 0.036), although there was no significant difference in BCVA improvement between the 2 groups (P \&gt; 0.05). In Group 3, IVTA and IVB did not have significant effects on CRT reduction and BCVA improvement (P \&gt; 0.05). CONCLUSION: The short-term efficacy of IVTA and IVB on treating clinically significant macular edema varied with different optical coherence tomography findings. In clinically significant macular edema combined with serous retinal detachment, IVTA may be more favorable than IVB in CRT reduction and BCVA improvement. In patients with diffused macular thickening, IVB may be better than IVTA in macular thickness reduction, although this does not translate to a significant improvement in BCVA.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000300},
	author = {Liu, Qingyun and Hu, Yijun and Yu, Honghua and Yuan, Ling and Hu, Jie and Atik, Alp and Guan, Meng and Li, Dongli and Li, Xin and Tang, Shibo}
}
@article {1478328,
	title = {Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	number = {1},
	year = {2020},
	month = {2020 Jan 07},
	pages = {573-583},
	abstract = {Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of -acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1912546116},
	author = {Liu, Cailing and Miyajima, Taiga and Melangath, Geetha and Miyai, Takashi and Vasanth, Shivakumar and Deshpande, Neha and Kumar, Varun and Ong Tone, Stephan and Gupta, Reena and Zhu, Shan and Vojnovic, Dijana and Chen, Yuming and Rogan, Eleanor G and Mondal, Bodhiswatta and Zahid, Muhammad and Jurkunas, Ula V}
}
@article {1814356,
	title = {Biogenic crocetin-crosslinked chitosan nanoparticles with high stability and drug loading for efficient radioprotection},
	journal = {Int J Biol Macromol},
	volume = {265},
	number = {Pt 1},
	year = {2024},
	month = {2024 Mar 10},
	pages = {130756},
	abstract = {The risk of radiation exposure increases with the development of nuclear energy and technology, and radiation protection receives more and more attention from public health and safety. However, the numerous adverse effects and low drug utilization limit the practical applications of radioprotective agents. In this study, we developed a biogenic crocetin-crosslinked chitosan nanoparticle with high stability and drug loading for efficient radioprotection. In detail, the nanoparticles were prepared using the natural antioxidant crocetin as a cross-linking reagent in amidation reactions of chitosan and mPEG-COOH. The nanoparticles exhibit a quick scavenging ability for common reactive oxygen species and reactive nitrogen in vitro. Meanwhile, cellular experiments demonstrate the good biocompatibility of the nanoparticles and the alleviation of radiation damage by scavenging reactive oxygen species, reducing apoptosis, and inhibiting DNA damage, etc. Importantly, the nanoparticles are effective in mitigating oxidative damage in major organs and maintaining peripheral blood cell content. In addition, they perform better radioprotective properties than free drug due to the significant extension of the blood half-life of crocetin in vivo from 10\&nbsp;min to 5\&nbsp;h. This work proposes a drug-crosslinking strategy for the design of a highly efficient radioprotective agent, which exhibits a promising prospect in the fields of nuclear emergency and public health.},
	issn = {1879-0003},
	doi = {10.1016/j.ijbiomac.2024.130756},
	author = {Liu, Chang and Wang, Lu and Zhou, Yi and Xia, Wanyi and Wang, Ziyu and Kuang, Liangju and Hua, Daoben}
}
@article {1363145,
	title = {Acute bilateral angle closure},
	journal = {JAMA Ophthalmol},
	volume = {131},
	number = {9},
	year = {2013},
	month = {2013 Sep},
	pages = {1231-2},
	keywords = {Acute Disease, Adult, Female, Fructose, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Migraine Disorders, Neuroprotective Agents, Tonometry, Ocular, Visual Acuity, Withholding Treatment},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.5186},
	author = {Liu, Yao and Rhee, Douglas J}
}
@article {1789036,
	title = {Altered brain network centrality in patients with orbital fracture: A resting-state functional MRI study},
	journal = {Exp Ther Med},
	volume = {26},
	number = {6},
	year = {2023},
	month = {2023 Dec},
	pages = {552},
	abstract = {The present study aimed to investigate potential functional network brain-activity abnormalities in individuals with orbital fracture (OF) using the voxel-wise degree centrality (DC) technique. The present study included 20 patients with OF (12 males and 8 females) and 20 healthy controls (HC; 12 males and 8 females), who were matched for gender, age and educational attainment. Functional magnetic resonance imaging (fMRI) in the resting state has been widely applied in several fields. Receiver operating characteristic (ROC) curves were calculated to distinguish between patients with OF and HCs. In addition, correlation analyses were performed between behavioral performance and average DC values in various locations. The DC technique was used to assess unprompted brain activity. Right cerebellum 9 region (Cerebelum_9_R) and left cerebellar peduncle 2 area (Cerebelum_Crus2_L) DC values of patients with OF were increased compared with those in HCs. Cerebelum_9_R and Cerebelum_Crus2_L had area under the ROC curve values of 0.983 and 1.000, respectively. Patients with OF appear to have several brain regions that exhibited aberrant brain network characteristics, which raises the possibility of neuropathic causes and offers novel therapeutic options.},
	issn = {1792-1015},
	doi = {10.3892/etm.2023.12251},
	author = {Liu, Yinuo and Gao, Yuxuan and Shu, Hui Ye and Li, Qiu Yu and Ge, Qian Min and Liao, Xu Lin and Pan, Yi Cong and Wu, Jieli and Su, Ting and Zhang, Li Juan and Liang, Rong Bin and Shao, Yi}
}
@article {341676,
	title = {Patient characteristics associated with artifacts in Spectralis optical coherence tomography imaging of the retinal nerve fiber layer in glaucoma.},
	journal = {Am J Ophthalmol},
	volume = {159},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {565-76.e2},
	abstract = {PURPOSE: To determine patient factors and eye conditions associated with artifacts in Spectralis optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) scans. DESIGN: Retrospective cross-sectional study. METHODS: The prevalence of 12 artifact types were described in this review of 2313 eye scans from 1188 patients who underwent a complete eye examination with Spectralis OCT scanning during the period of September 2009 to July 2013. The generalized estimating equations model was used to analyze associations between increased artifact prevalence and 10 patient characteristics, which included age, sex, race, visual acuity, refractive error, astigmatism, cataract status, glaucoma staging, visual field reliability, and glaucoma diagnosis. RESULTS: A total of 1070 or 46.3\% of the 2313 eye scans had at least 1 artifact. Decentration error was the most common artifact (27.8\%), followed by posterior vitreous detachment artifacts (14.4\%). Visual acuity of less than 20/40 (P\&nbsp;\&lt; .0001), presence of moderate to severe cataracts (P\&nbsp;\&lt; .0001), advanced stage of glaucoma (P \&lt; .0001), and a diagnosis of open-angle glaucoma (P\&nbsp;= .0003) were associated with increased prevalence of artifacts. CONCLUSIONS: Clinicians should first assess scans for artifacts before making therapeutic decisions based on RNFL thickness measurements.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.12.006},
	author = {Liu, Yingna and Simavli, Huseyin and Que, Christian John and Rizzo, Jennifer L and Tsikata, Edem and Maurer, Rie and Chen, Teresa C}
}
@article {1504074,
	title = {Repair of Tube Erosion by Modifying the Tube Extender},
	journal = {J Glaucoma},
	volume = {29},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {604-606},
	abstract = {We describe here a case report of a novel technique for tube erosion repair, which modifies and utilizes the commercially available tube extender (Model TE). The modification of the tube extender makes the commercially available tube extender more compact and is useful in cases where conjunctival mobility and space are limited. This debulking of the tube extender may reduce the risk of future tube exposure and dellen formation.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001505},
	author = {Liu, Wendy W and Werner, Astrid and Chen, Teresa C}
}
@article {1364507,
	title = {Expression of wild-type Rp1 protein in Rp1 knock-in mice rescues the retinal degeneration phenotype},
	journal = {PLoS One},
	volume = {7},
	number = {8},
	year = {2012},
	month = {2012},
	pages = {e43251},
	abstract = {Mutations in the retinitis pigmentosa 1 (RP1) gene are a common cause of autosomal dominant retinitis pigmentosa (adRP), and have also been found to cause autosomal recessive RP (arRP) in a few families. The 33 dominant mutations and 6 recessive RP1 mutations identified to date are all nonsense or frameshift mutations, and almost exclusively (38 out of 39) are located in the 4(th) and final exon of RP1. To better understand the underlying disease mechanisms of and help develop therapeutic strategies for RP1 disease, we performed a series of human genetic and animal studies using gene targeted and transgenic mice. Here we report that a frameshift mutation in the 3(rd) exon of RP1 (c.686delC; p.P229QfsX35) found in a patient with recessive RP1 disease causes RP in the homozygous state, whereas the heterozygous carriers are unaffected, confirming that haploinsufficiency is not the causative mechanism for RP1 disease. We then generated Rp1 knock-in mice with a nonsense Q662X mutation in exon 4, as well as Rp1 transgenic mice carrying a wild-type BAC Rp1 transgene. The Rp1-Q662X allele produces a truncated Rp1 protein, and homozygous Rp1-Q662X mice experience a progressive photoreceptor degeneration characterized disorganization of photoreceptor outer segments. This phenotype could be prevented by expression of a normal amount of Rp1 protein from the BAC transgene without removal of the mutant Rp1-Q662X protein. Over-expression of Rp1 protein in additional BAC Rp1 transgenic lines resulted in retinal degeneration. These findings suggest that the truncated Rp1-Q662X protein does not exert a toxic gain-of-function effect. These results also imply that in principle gene augmentation therapy could be beneficial for both recessive and dominant RP1 patients, but the levels of RP1 protein delivered for therapy will have to be carefully controlled.},
	keywords = {Adult, Alleles, Animals, Base Sequence, Exons, Eye Proteins, Gene Expression Regulation, Gene Knock-In Techniques, Genetic Therapy, Haploinsufficiency, Humans, Mice, Mice, Transgenic, Phenotype, Photoreceptor Cells, Retinal Degeneration, Sequence Deletion},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0043251},
	author = {Liu, Qin and Collin, Rob W J and Cremers, Frans P M and den Hollander, Anneke I and van den Born, L Ingeborgh and Pierce, Eric A}
}
@article {1490451,
	title = {Effect of partial posterior vitreous detachment on spectral-domain optical coherence tomography retinal nerve fibre layer thickness measurements},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {11},
	year = {2020},
	month = {2020 Nov},
	pages = {1524-1527},
	abstract = {BACKGROUND/AIMS: To assess the effect of partial posterior vitreous detachment (pPVD) on spectral-domain optical coherence tomography (OCT) peripapillary retinal nerve fibre layer thickness (RNFL) measurements. METHODS: Spectral-domain OCT RNFL thickness measurements were obtained from 684 consecutive patients who were seen in the Massachusetts Eye and Ear Glaucoma Service. Of these patients, we compared RNFL thickness measurements between 101 eyes of 101 glaucoma suspects who met inclusion criteria (55 eyes with and 46 eyes without pPVD). RESULTS: Among all 684 patients, 253 (37\%) had pPVD in at least one eye. Among a subset of 101 eyes of 101 glaucoma suspects, average RNFL thickness was greater in eyes with compared to eyes without pPVD (p=0.02). Measurements were significantly greater in the inferior (p=0.004) and superior quadrants (p=0.008), but not in the nasal (p=0.10) and temporal quadrants (p=0.25). The difference in average RNFL thickness remained significant (p=0.05) even when corrected for expected age-related decline in RNFL thickness. CONCLUSION: Over a third of patients were found on peripapillary spectral-domain OCT to have a pPVD, which was associated with greater RNFL thickness measurements. Judicious clinical interpretation of this finding on spectral-domain OCT RNFL thickness scans should be factored into the assessment of glaucoma suspects.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-314570},
	author = {Liu, Yao and Baniasadi, Neda and Ratanawongphaibul, Kitiya and Chen, Teresa C}
}
@article {1528421,
	title = {Glycolysis links reciprocal activation of myeloid cells and endothelial cells in the retinal angiogenic niche},
	journal = {Sci Transl Med},
	volume = {12},
	number = {555},
	year = {2020},
	month = {2020 08 05},
	abstract = {The coordination of metabolic signals among different cellular components in pathological retinal angiogenesis is poorly understood. Here, we showed that in the pathological angiogenic vascular niche, retinal myeloid cells, particularly macrophages/microglia that are spatially adjacent to endothelial cells (ECs), are highly glycolytic. We refer to these macrophages/microglia that exhibit a unique angiogenic phenotype with increased expression of both M1 and M2 markers and enhanced production of both proinflammatory and proangiogenic cytokines as pathological retinal angiogenesis-associated glycolytic macrophages/microglia (PRAGMs). The phenotype of PRAGMs was recapitulated in bone marrow-derived macrophages or retinal microglia stimulated by lactate that was produced by hypoxic retinal ECs. Knockout of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (; for rodents), a glycolytic activator in myeloid cells, impaired the ability of macrophages/microglia to acquire an angiogenic phenotype, rendering them unable to promote EC proliferation and sprouting and pathological neovascularization in a mouse model of oxygen-induced proliferative retinopathy. Mechanistically, hyperglycolytic macrophages/microglia produced large amount of acetyl-coenzyme A, leading to histone acetylation and PRAGM-related gene induction, thus reprogramming macrophages/microglia into an angiogenic phenotype. These findings reveal a critical role of glycolytic metabolites as initiators of reciprocal activation of macrophages/microglia and ECs in the retinal angiogenic niche and suggest that strategies targeting the metabolic communication between these cell types may be efficacious in the treatment of pathological retinal angiogenesis.},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.aay1371},
	author = {Liu, Zhiping and Xu, Jiean and Ma, Qian and Zhang, Xiaoyu and Yang, Qiuhua and Wang, Lina and Cao, Yapeng and Xu, Zhimin and Tawfik, Amany and Sun, Ye and Weintraub, Neal L and Fulton, David J and Hong, Mei and Dong, Zheng and Smith, Lois E H and Caldwell, Ruth B and Sodhi, Akrit and Huo, Yuqing}
}
@article {1460376,
	title = {Diagnostic Capability of 3D Peripapillary Retinal Volume for Glaucoma Using Optical Coherence Tomography Customized Software},
	journal = {J Glaucoma},
	volume = {28},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {708-717},
	abstract = {PR{\'e}CIS:: The diagnostic capability of peripapillary retinal volume is similar to peripapillary retinal nerve fiber layer thickness for diagnosing glaucoma, but with fewer artifacts. PURPOSE: To compare the diagnostic capability of 3-dimensional peripapillary retinal volume (RV) versus 2-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness for open-angle glaucoma. PATIENTS AND METHODS: A retrospective cross-sectional analysis was conducted. A total of 180 subjects (113 open-angle glaucoma, 67 normal participants) had spectral domain optical coherence tomography volume scans and RNFL thickness measurements. Peripapillary RV values were calculated using a custom-designed program with 4 circumpapillary annuli (CA): CA1 had circle diameters of 2.5 and 3.5 mm; CA2, 3 and 4 mm; CA3, 3.5 and 4.5 mm; and CA4, 4 and 5 mm. Area under the receiver operating characteristic curves were calculated for global, quadrant, and octant regions for RV (CA1 to CA4) and RNFL thickness. Pair-wise comparisons were conducted. Artifacts rates were determined. RESULTS: Mean age was 62.7{\textpm}15.4 years, and 47.8\% (86/180) were male. Among RV measurements, best diagnostic performances were for the smallest 2 annuli for inferior RV (CA1: 0.964, CA2: 0.955). Of the 4 annuli, CA1 had the highest diagnostic performance. Of specific regions, the inferior RV quadrant had the highest performance across CA1 to CA4. Peripapillary RV had similar diagnostic capability compared with RNFL thickness (P\&gt;0.05). The artifact rate per B-scan for RV was 6.0\%, which was significantly lower compared with 2-dimensional RNFL thickness in the same patient population (32.2\%, P\&lt;0.0001). CONCLUSIONS: The diagnostic capability of RV is similar to RNFL thickness for perimetric open-angle glaucoma, but RV had fewer artifacts compared with RNFL thickness.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001291},
	author = {Liu, Yingna and Jassim, Firas and Braaf, Boy and Khoueir, Ziad and Poon, Linda Yi-Chieh and Ben-David, Geulah S and Papadogeorgou, Georgia and Tsikata, Edem and Simavli, Huseyin and Que, Christian and Lee, Ramon and Shieh, Eric and Vakoc, Benjamin J and Bouma, Brett E and de Boer, Johannes F and Chen, Teresa C}
}
@article {1323934,
	title = {Diabetic Retinopathy Assessment Variability Among Eye Care Providers in an Urban Teleophthalmology Program},
	journal = {Telemed J E Health},
	volume = {25},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {301-308},
	abstract = {BACKGROUND: Teleophthalmology is an evidence-based method for diabetic eye screening. It is unclear whether the type of eye care provider performing teleophthalmology interpretation produces significant variability. INTRODUCTION: We assessed grading variability between an optometrist, general ophthalmologist, and retinal specialist using images from an urban, diabetic retinopathy teleophthalmology program. METHODS: Three readers evaluated digital retinal images in 100 cases (178 eyes from 90 patients with type 2 diabetes). Fisher{\textquoteright}s exact test, percent agreement, and the observed proportion of positive (P) or negative agreement (P) were used to assess variability. RESULTS: Among cases deemed gradable by all three readers (n = 65), there was substantial agreement on absence of any retinopathy (88\% {\textpm} 4.6\%, P = 0.91-0.95), presence of moderate nonproliferative or worse retinopathy (87\% {\textpm} 3.9\%, P = 0.67-1.00), and presence of macular edema (99\% {\textpm} 0.9\%, P = 0.67-1.00). There was limited agreement regarding presence of referable nondiabetic eye pathology (61\% {\textpm} 11\%, P = 0.21-0.59) and early, nonroutine referral for a follow-up clinical eye exam (66\% {\textpm} 8.1\%, P = 0.19-0.54). Among all cases (n = 100), there was acceptable agreement regarding which had gradable images (77\% {\textpm} 5.0\%, P = 0.50-0.90). DISCUSSION: Inclusion of multiple types of eye care providers as teleophthalmology readers is unlikely to produce significant variability in the assessment of diabetic retinopathy among high-quality images. Greater variability was found regarding image gradability, nondiabetic eye pathology, and recommended clinical referral times. CONCLUSIONS: Our results suggest that more extensive training and uniform referral standards are needed to improve consensus on image gradability, referable nondiabetic eye pathology, and recommended clinical referral times.},
	issn = {1556-3669},
	doi = {10.1089/tmj.2018.0019},
	author = {Liu, Yao and Rajamanickam, Victoria P and Parikh, Ravi S and Loomis, Stephanie J and Kloek, Carolyn E and Kim, Leo A and Hitchmoth, Dorothy L and Song, Brian J and Xerras, Dean C and Pasquale, Louis R}
}
@article {1402583,
	title = {Hypoxia: A breath of fresh air for the meibomian gland},
	journal = {Ocul Surf},
	year = {2018},
	month = {2018 Dec 04},
	abstract = {PURPOSE: Optimal meibomian gland (MG) function is critically important for the health and wellbeing of the ocular surface. We hypothesize that low oxygen (O) conditions promote the function of human MG epithelial cells (HMGECs) and that human MGs exist in a relatively hypoxic environment. The purpose of this study was to test our hypotheses. METHODS: We used human and mouse eyelid segments, and immortalized human MG epithelial cells (IHMGECs) in our studies. To evaluate oxygen (O) levels in the mouse MG and vicinity, we injected pimonidazole (pimo), a hypoxia marker, before sacrifice. Human eyelid samples were stained with the hypoxia marker glucose transporter 1 (Glut-1). To determine the effect of low O levels on IHMGECs, we cultured cells under proliferating and differentiating conditions in both normoxic (21\% O) and hypoxic (3\% O) conditions for 5-15 days. IHMGECs were evaluated for cell number, neutral lipid content, lysosome accumulation, expression of biomarker proteins and DNase II activity. RESULTS: Our results demonstrate that human and mouse MGs, but not the surrounding connective tissue, exist in a relatively hypoxic environment in vivo. In addition, our findings show that hypoxia does not influence IHMGEC numbers in basal or proliferating culture conditions, but does stimulate the expression of SREBP-1 in differentiating IHMGECs. Hypoxia also significantly increased DNase II activity, and apparently IHMGEC terminal differentiation. CONCLUSIONS: Our Results support our hypotheses, and indicate that relative hypoxia promotes MG function.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.12.001},
	author = {Liu, Yang and Chen, Di and Chen, Xiaomin and Kam, Wendy R and Hatton, Mark P and Sullivan, David A}
}
@article {382416,
	title = {Can tetracycline antibiotics duplicate the ability of azithromycin to stimulate human meibomian gland epithelial cell differentiation?},
	journal = {Cornea},
	volume = {34},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {342-6},
	abstract = {PURPOSE: Azithromycin and tetracyclines are commonly prescribed in the United States for the treatment of meibomian gland dysfunction (MGD). The efficacy of these antibiotics has been believed to be their antiinflammatory and antibacterial actions, which suppress MGD-associated posterior blepharitis and growth of lid bacteria. However, we recently discovered that azithromycin can act directly on human meibomian gland epithelial cells (HMGECs) to stimulate their function. In this study, we sought to determine whether tetracycline antibiotics can duplicate this azithromycin effect. METHODS: Immortalized HMGEC were cultured in the presence of a vehicle, azithromycin, doxycycline, minocycline, or tetracycline for 5 days. Cells were evaluated for cholesterol and neutral lipid staining, and the lipid composition of cellular lysates was analyzed by high-performance thin-layer chromatography. RESULTS: Our results demonstrate that azithromycin{\textquoteright}s ability to stimulate the differentiation of human meibomian gland cells is unique, and is not duplicated by doxycycline, minocycline, or tetracycline. Azithromycin, but not the other antibiotics, significantly increased the cellular accumulation of cholesterol, cholesterol esters, phospholipids, and lysosomes. These differentiative actions of azithromycin were paralleled by an increased expression of sterol regulatory element-binding protein 1. CONCLUSIONS: Our findings show that the stimulatory effects of azithromycin on HMGEC function are unique and are not duplicated by the antibiotics doxycycline, minocycline, or tetracycline. Our results further suggest that this stimulatory influence of azithromycin may contribute to its beneficial effect in treating MGD and its associated evaporative dry eye disease.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000351},
	author = {Liu, Yang and Kam, Wendy R and Ding, Juan and Sullivan, David A}
}
@article {1532343,
	title = {Three-dimensional Neuroretinal Rim Thickness and Visual Fields in Glaucoma: A Broken-stick Model},
	journal = {J Glaucoma},
	volume = {29},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {952-963},
	abstract = {PRECIS: In open-angle glaucoma, when neuroretinal rim tissue measured by volumetric optical coherence tomography (OCT) scans is below a third of the normal value, visual field (VF) damage becomes detectable. PURPOSE: To determine the amount of neuroretinal rim tissue thickness below which VF damage becomes detectable. METHODS: In a retrospective cross-sectional study, 1 eye per subject (of 57 healthy and 100 open-angle glaucoma patients) at an academic institution had eye examinations, VF testing, spectral-domain OCT retinal nerve fiber layer (RNFL) thickness measurements, and optic nerve volumetric scans. Using custom algorithms, the minimum distance band (MDB) neuroretinal rim thickness was calculated from optic nerve scans. "Broken-stick" regression was performed for estimating both the MDB and RNFL thickness tipping-point thresholds, below which were associated with initial VF defects in the decibel scale. The slopes for the structure-function relationship above and below the thresholds were computed. Smoothing curves of the MDB and RNFL thickness covariates were evaluated to examine the consistency of the independently identified tipping-point pairs. RESULTS: Plots of VF total deviation against MDB thickness revealed plateaus of VF total deviation unrelated to MDB thickness. Below the thresholds, VF total deviation decreased with MDB thickness, with the associated slopes significantly greater than those above the thresholds (P\&lt;0.014). Below 31\% of global MDB thickness, and 36.8\% and 43.6\% of superior and inferior MDB thickness, VF damage becomes detectable. The MDB and RNFL tipping points were in good accordance with the correlation of the MDB and RNFL thickness covariates. CONCLUSIONS: When neuroretinal rim tissue, characterized by MDB thickness in OCT, is below a third of the normal value, VF damage in the decibel scale becomes detectable.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001604},
	author = {Liu, Wendy W and McClurkin, Michael and Tsikata, Edem and Hui, Pui-Chuen and Tobias Elze and Celebi, Ali R C and Khoueir, Ziad and Lee, Ramon and Shieh, Eric and Simavli, Huseyin and Que, Christian and Guo, Rong and de Boer, Johannes and Chen, Teresa C}
}
@article {1125351,
	title = {Acetylation and deacetylation in cancer stem-like cells},
	journal = {Oncotarget},
	year = {2017},
	month = {2017 Jul 11},
	abstract = {Cancer stem-like cell (CSC) model has been established to investigate the underlying mechanisms of tumor initiation and progression. The imbalance between acetylation and deacetylation of histone or non-histone proteins, one of the important epigenetic modification processes, is closely associated with a wide variety of diseases including cancer. Acetylation and deacetylation are involved in various stemness-related signal pathways and drive the regulation of self-renewal and differentiation in normal developmental processes. Therefore, it is critical to explore their role in the maintenance of cancer stem-like cell traits. Here, we will review the extensive dysregulations of acetylation found in cancers and summarize their functional roles in sustaining CSC-like properties. Additionally, the use of deacetyltransferase inhibitors as an effective therapeutic strategy against CSCs is also discussed.},
	issn = {1949-2553},
	doi = {10.18632/oncotarget.19167},
	author = {Liu, Na and Li, Shiqi and Wu, Nan and Cho, Kin-Sang}
}
@article {1661594,
	title = {Disparities in Access to Corneal Tissue in the Developing World},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {183-189},
	abstract = {Corneal disease is a leading cause of blindness worldwide. For most blinding corneal conditions, keratoplasty is the only way of restoring sight. Unfortunately, access to corneal transplantation is widely variable, most notably due to the lack of suitable donor material. There exists significant disparity between the developed and developing world when it comes to access to cornea tissue, with supply often inversely proportional to burden of disease. The purpose of this review is to identify the current disparities in supply and demand of corneal donor tissue, understand how to access corneal tissue, and propose solutions that promote equitable care for patients with severe corneal disease.},
	keywords = {Blindness, Cornea, Corneal Diseases, Corneal Transplantation, Humans, Tissue Donors},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152714},
	author = {Liu, Catherine and Saeed, Hajirah N}
}
@article {341711,
	title = {DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {12},
	year = {2014},
	month = {2014 Dec},
	pages = {8251-8},
	abstract = {PURPOSE: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG). METHODS: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non-blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those >=5 kilobases (kb) in size and interrogated by >=5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC. RESULTS: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls. CONCLUSIONS: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15712},
	author = {Liu, Yutao and Garrett, Melanie E and Yaspan, Brian L and Bailey, Jessica Cooke and Loomis, Stephanie J and Brilliant, Murray and Budenz, Donald L and Christen, William G and Fingert, John H and Gaasterland, Douglas and Gaasterland, Terry and Kang, Jae H and Lee, Richard K and Lichter, Paul and Moroi, Sayoko E and Realini, Anthony and Richards, Julia E and Schuman, Joel S and Scott, William K and Singh, Kuldev and Sit, Arthur J and Vollrath, Douglas and Weinreb, Robert and Wollstein, Gadi and Zack, Donald J and Zhang, Kang and Pericak-Vance, Margaret A and Haines, Jonathan L and Pasquale, Louis R and Wiggs, Janey L and Allingham, R Rand and Ashley-Koch, Allison E and Hauser, Michael A}
}
@article {1363146,
	title = {Correlation of cytokine levels and microglial cell infiltration during retinal degeneration in RCS rats},
	journal = {PLoS One},
	volume = {8},
	number = {12},
	year = {2013},
	month = {2013},
	pages = {e82061},
	abstract = {Microglial cells, which are immunocompetent cells, are involved in all diseases of the central nervous system. During their activation in various diseases, a variety of soluble factors are released. In the present study, the correlation between cytokine levels and microglial cell migration in the course of retinal degeneration of Royal College of Surgeons (RCS) rats was evaluated. MFG-E8 and CD11b were used to confirm the microglial cells. In the retina of RCS rats, the mRNA expression of seven genes (MFG-E8 and its integrins αυ and {\ss}5, CD11b and the cytokines TNF-α, IL-1{\ss}, and MCP-1) formed almost similar bimodal peak distributions, which were centred at P7 and P45 to P60. In contrast, in rdy rats, which comprised the control group, a unimodal peak distribution centred at P14 was observed. The gene expression accompanied the activation and migration of microglial cells from the inner to the outer layer of the retina during the process of degeneration. Principal component analysis and discriminant function analysis revealed that the expression of these seven genes, especially TNF-α and CD11b, positively correlated with retinal degeneration and microglial activity during retinal degeneration in RCS rats, but not in the control rats. Furthermore, linear regression analysis demonstrated a significant correlation between the expression of these genes and the activation of microglial cells in the dystrophic retina. Our findings suggest that the suppression of microglial cells and the blockade of their cytotoxic effects may constitute a novel therapeutic strategy for treating photoreceptor death in various retinal disorders.},
	keywords = {Animals, Antigens, Surface, Cell Movement, Cell Shape, Cytokines, Gene Expression Regulation, Inflammation, Integrins, Male, Microglia, Milk Proteins, Rats, Retina, Retinal Degeneration, Retinal Ganglion Cells, RNA, Messenger},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0082061},
	author = {Liu, Yong and Yang, Xuesen and Utheim, Tor Paaaske and Guo, Chenying and Xiao, Mingchun and Liu, Yan and Yin, Zhengqin and Ma, Jie}
}
@article {1814346,
	title = {Automated detection of nine infantile fundus diseases and conditions in retinal images using a deep learning system},
	journal = {EPMA J},
	volume = {15},
	number = {1},
	year = {2024},
	month = {2024 Mar},
	pages = {39-51},
	abstract = {PURPOSE: We developed an Infant Retinal Intelligent Diagnosis System (IRIDS), an automated system to aid early diagnosis and monitoring of infantile fundus diseases and\&nbsp;health conditions to satisfy urgent needs of\&nbsp;ophthalmologists. METHODS: We developed IRIDS by combining convolutional neural networks and transformer structures, using a dataset of 7697 retinal images (1089 infants) from four hospitals. It identifies nine fundus diseases and conditions, namely, retinopathy of prematurity (ROP) (mild ROP, moderate ROP, and severe ROP), retinoblastoma (RB), retinitis pigmentosa (RP), Coats disease, coloboma of the choroid, congenital retinal fold (CRF), and normal. IRIDS also includes depth attention modules, ResNet-18 (Res-18), and Multi-Axis Vision Transformer (MaxViT). Performance was compared to that of ophthalmologists using 450 retinal images. The IRIDS employed a five-fold cross-validation approach to generate the classification results. RESULTS: Several baseline models achieved the following metrics: accuracy, precision, recall, F1-score (F1), kappa, and area under the receiver operating characteristic curve (AUC) with best values of 94.62\% (95\% CI, 94.34\%-94.90\%), 94.07\% (95\% CI, 93.32\%-94.82\%), 90.56\% (95\% CI, 88.64\%-92.48\%), 92.34\% (95\% CI, 91.87\%-92.81\%), 91.15\% (95\% CI, 90.37\%-91.93\%), and 99.08\% (95\% CI, 99.07\%-99.09\%), respectively. In comparison, IRIDS showed promising results compared to ophthalmologists, demonstrating an average accuracy, precision, recall, F1, kappa, and AUC of 96.45\% (95\% CI, 96.37\%-96.53\%), 95.86\% (95\% CI, 94.56\%-97.16\%), 94.37\% (95\% CI, 93.95\%-94.79\%), 95.03\% (95\% CI, 94.45\%-95.61\%), 94.43\% (95\% CI, 93.96\%-94.90\%), and 99.51\% (95\% CI, 99.51\%-99.51\%), respectively, in multi-label classification on the test dataset, utilizing the Res-18 and MaxViT models. These results suggest that, particularly in terms of AUC, IRIDS achieved performance that warrants further investigation for the detection of retinal abnormalities. CONCLUSIONS: IRIDS identifies nine infantile fundus diseases and conditions accurately. It may aid non-ophthalmologist personnel in underserved areas in infantile fundus disease screening. Thus, preventing severe complications. The IRIDS serves as an example of artificial intelligence integration into ophthalmology to achieve better outcomes in predictive, preventive, and personalized medicine (PPPM\&nbsp;/\&nbsp;3PM) in the treatment of infantile fundus diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00350-y.},
	issn = {1878-5077},
	doi = {10.1007/s13167-024-00350-y},
	author = {Liu, Yaling and Xie, Hai and Zhao, Xinyu and Tang, Jiannan and Yu, Zhen and Wu, Zhenquan and Tian, Ruyin and Chen, Yi and Chen, Miaohong and Ntentakis, Dimitrios P and Du, Yueshanyi and Chen, Tingyi and Hu, Yarou and Zhang, Sifan and Lei, Baiying and Zhang, Guoming}
}
@article {1445350,
	title = {MicroRNA-145 Regulates Pathological Retinal Angiogenesis by Suppression of TMOD3},
	journal = {Mol Ther Nucleic Acids},
	volume = {16},
	year = {2019},
	month = {2019 Jun 07},
	pages = {335-347},
	abstract = {Pathological angiogenesis is a hallmark of various vascular diseases, including vascular eye disorders. Dysregulation of microRNAs (miRNAs), a group of small regulatory RNAs, has been implicated in the regulation of ocular neovascularization. This study investigated the specific role of microRNA-145 (miR-145) in regulating vascular endothelial cell (EC) function and pathological ocular angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). Expression of miR-145 was significantly upregulated in OIR mouse retinas compared with room air controls. Treatment with synthetic miR-145 inhibitors drastically decreased levels of pathological neovascularization in OIR, without substantially affecting normal developmental angiogenesis. In cultured human retinal ECs, treatment with miR-145 mimics significantly increased the EC angiogenic function, including proliferation, migration, and tubular formation, whereas miR-145 inhibitors attenuated in\&nbsp;vitro angiogenesis. Tropomodulin3 (TMOD3), an actin-capping protein, is a direct miR-145 target and is downregulated in OIR retinas. Treatment with miR-145 mimic led to TMOD3 inhibition, altered actin cytoskeletal architecture, and elongation of ECs. Moreover, inhibition of TMOD3 promoted EC angiogenic function and pathological neovascularization in OIR and abolished the vascular effects of miR-145 inhibitors in\&nbsp;vitro and in\&nbsp;vivo. Overall, our findings indicate that miR-145 is a novel regulator of TMOD3-dependent cytoskeletal architecture and pathological angiogenesis and a potential target for development of treatments for neovascular eye disorders.},
	issn = {2162-2531},
	doi = {10.1016/j.omtn.2019.03.001},
	author = {Liu, Chi-Hsiu and Wang, Zhongxiao and Huang, Shuo and Sun, Ye and Chen, Jing}
}
@article {931111,
	title = {Evidence-Based Endothelial Rehabilitation.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	pages = {96-103},
	abstract = {Endothelial keratoplasty (EK) has replaced penetrating keratoplasty (PKP) as the preferred surgical therapy for corneal endothelial dysfunction. However, recent nationwide corneal graft registry data showed few advantages to EK relative to PKP with respect to graft survival and visual outcomes. This article compares the published outcomes and complications of EK to those of PKP. EK demonstrates superior spectacle corrected visual outcomes, fast recovery, less graft rejection, and higher patient satisfaction, particularly in studies performed by high-volume surgeons/centers. Endothelial cell loss in EK, while higher at early time points, was equivalent or superior at five-years{\textquoteright} follow-up and graft survival was equivalent to or superior to PKP in these centers/studies. Continued standardization and simplification of EK procedures may allow surgeons who perform a lower volume of EK to achieve results that mirror those of high-volume centers/surgeons and close the potential gap in outcomes demonstrated in the registry data.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228409},
	author = {Liu, Shaohui and Veldman, Peter}
}
@article {1364508,
	title = {IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation},
	journal = {PLoS One},
	volume = {7},
	number = {5},
	year = {2012},
	month = {2012},
	pages = {e36949},
	abstract = {Many molecular and cellular abnormalities detected in the diabetic retina support a role for IL-1β-driven neuroinflammation in the pathogenesis of diabetic retinopathy. IL-1β is well known for its role in the induction and, through autostimulation, amplification of neuroinflammation. Upregulation of IL-1β has been consistently detected in the diabetic retina; however, the mechanisms and cellular source of IL-1β overexpression are poorly understood. The aim of this study was to investigate the effect of high glucose and IL-1β itself on IL-1β expression in microglial, macroglial (astrocytes and M{\"u}ller cells) and retinal vascular endothelial cells; and to study the effect of diabetes on the expression of IL-1β in isolated retinal vessels and on the temporal pattern of IL-1β upregulation and glial reactivity in the retina of streptozotocin-diabetic rats. IL-1β was quantified by RealTime RT-PCR and ELISA, glial fibrillar acidic protein, α2-macroglobulin, and ceruloplasmin by immunoblotting. We found that high glucose induced a 3-fold increase of IL-1β expression in retinal endothelial cells but not in macroglia and microglia. IL-1β induced its own synthesis in endothelial and macroglial cells but not in microglia. In retinal endothelial cells, the high glucose-induced IL-1β overexpression was prevented by calphostin C, a protein kinase C inhibitor. The retinal vessels of diabetic rats showed increased IL-1β expression as compared to non-diabetic rats. Retinal expression of IL-1β increased early after the induction of diabetes, continued to increase with progression of the disease, and was temporally associated with upregulation of markers of glial activation. These findings point to hyperglycemia as the trigger and to the endothelium as the origin of the initial retinal upregulation of IL-1β in diabetes; and to IL-1β itself, via autostimulation in endothelial and macroglial cells, as the mechanism of sustained IL-1β overexpression. Interrupting the vicious circle triggered by IL-1β autostimulation could limit the progression of diabetic retinopathy.},
	keywords = {alpha-Macroglobulins, Animals, Astrocytes, Ceruloplasmin, Diabetes Mellitus, Experimental, Diabetic Retinopathy, Endothelial Cells, Endothelium, Glial Fibrillary Acidic Protein, Glucose, Hyperglycemia, Interleukin-1beta, Male, Microglia, Neuroglia, Protein Kinase C, Random Allocation, Rats, Rats, Sprague-Dawley, Rats, Wistar, Retina, Retinal Vessels, Up-Regulation},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0036949},
	author = {Liu, Yang and Biarn{\'e}s Costa, Montserrat and Chiara Gerhardinger}
}
@article {560236,
	title = {Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {112},
	number = {39},
	year = {2015},
	month = {2015 Sep 29},
	pages = {12163-8},
	abstract = {Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1508426112},
	author = {Liu, Chi-Hsiu and Sun, Ye and Li, Jie and Gong, Yan and Tian, Katherine T and Evans, Lucy P and Morss, Peyton C and Fredrick, Thomas W and Saba, Nicholas J and Chen, Jing}
}
@article {1762021,
	title = {Mechanosensitive ion channel gene survey suggests potential roles in primary open angle glaucoma},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Sep 23},
	pages = {15871},
	abstract = {Although glaucoma is a disease modulated by eye pressure, the mechanisms of pressure sensing in the eye are not well understood. Here, we investigated associations between mechanosensitive ion channel gene variants and primary open-angle glaucoma (POAG). Common (minor allele frequency \&gt; 5\%) single nucleotide polymorphisms located within the genomic regions of 20 mechanosensitive ion channel genes in the K2P, TMEM63, PIEZO and TRP channel families were assessed using genotype data from the NEIGHBORHOOD consortium of 3853 cases and 33,480 controls. Rare (minor allele frequency \&lt; 1\%) coding variants were assessed using exome array genotyping data for 2606 cases and 2606 controls. Association with POAG was analyzed using logistic regression adjusting for age and sex. Two rare PIEZO1 coding variants with protective effects were identified in the NEIGHBOR dataset: R1527H, (OR 0.17, P = 0.0018) and a variant that alters a canonical splice donor site, g.16-88737727-C-G Hg38 (OR 0.38, P = 0.02). Both variants showed similar effects in the UK Biobank and the R1527H also in the FinnGen database. Several common variants also reached study-specific thresholds for association in the NEIGHBORHOOD dataset. These results identify novel variants in several mechanosensitive channel genes that show associations with POAG, suggesting that these channels may be potential therapeutic targets.},
	keywords = {Databases, Factual, Exome, Genotype, Glaucoma, Open-Angle, Humans, Ion Channels},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-43072-3},
	author = {Liu, Wendy W and Kinzy, Tyler G and Cooke Bailey, Jessica N and Xu, Zihe and Hysi, Pirro and Wiggs, Janey L and NEIGHBORHOOD Consortium}
}
@article {1483606,
	title = {MicroRNAs in Vascular Eye Diseases},
	journal = {Int J Mol Sci},
	volume = {21},
	number = {2},
	year = {2020},
	month = {2020 Jan 19},
	abstract = {Since the discovery of the first microRNA (miRNA) decades ago, studies of miRNA biology have expanded in many biomedical research fields, including eye research. The critical roles of miRNAs in normal development and diseases have made miRNAs useful biomarkers or molecular targets for potential therapeutics. In the eye, ocular neovascularization (NV) is a leading cause of blindness in multiple vascular eye diseases. Current anti-angiogenic therapies, such as anti-vascular endothelial growth factor (VEGF) treatment, have their limitations, indicating the need for investigating new targets. Recent studies established the roles of various miRNAs in the regulation of pathological ocular NV, suggesting miRNAs as both biomarkers and therapeutic targets in vascular eye diseases. This review summarizes the biogenesis of miRNAs, and their functions in the normal development and diseases of the eye, with a focus on clinical and experimental retinopathies in both human and animal models. Discovery of novel targets involving miRNAs in vascular eye diseases will provide insights for developing new treatments to counter ocular NV.},
	issn = {1422-0067},
	doi = {10.3390/ijms21020649},
	author = {Liu, Chi-Hsiu and Huang, Shuo and Britton, William R and Chen, Jing}
}
@article {313106,
	title = {Decreased DJ-1 leads to impaired Nrf2-regulated antioxidant defense and increased UV-A-induced apoptosis in corneal endothelial cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {9},
	year = {2014},
	month = {2014 Jul 31},
	pages = {5551-60},
	abstract = {PURPOSE: To investigate the role of DJ-1 in Nrf2-regulated antioxidant defense in corneal endothelial cells (CECs) at baseline and in response to ultraviolet A (UV-A)-induced oxidative stress. METHODS: DJ-1-deficient CECs were obtained by transfection of an immortalized normal human corneal endothelial cell line (HCECi) with DJ-1 small interfering RNA (siRNA) or by isolation of CECs from ex vivo corneas of DJ-1 knockout mice. Levels of reactive oxygen species (ROS), protein carbonyls, Nrf2 subcellular localization, Nrf2 target genes, and protein interaction between Keap1/Nrf2 and Cul3/Nrf2 were compared between normal and DJ-1-deficient CECs. Oxidative stress was induced by irradiating HCECi cells with UV-A, and cell death and levels of activated caspase3 and phospho-p53 were determined. RESULTS: DJ-1 siRNA-treated cells exhibited increased levels of ROS production and protein carbonyls as well as a 2.2-fold decrease in nuclear Nrf2 protein when compared to controls. DJ-1 downregulation led to attenuated gene expression of Nrf2 and its target genes HO-1 and NQO1. Similar levels of Nrf2 inhibitor, Keap1, and Cul3/Nrf2 and Keap1/Nrf2 were observed in DJ-1 siRNA-treated cells as compared to controls. Ultraviolet A irradiation resulted in a 3.0-fold increase in cell death and elevated levels of activated caspase3 and phospho-p53 in DJ-1 siRNA-treated cells compared to controls. CONCLUSIONS: Downregulation of DJ-1 impairs nuclear translocation of Nrf2, causing decreased antioxidant gene expression and increased oxidative damage. The decline in DJ-1 levels leads to heightened CEC susceptibility to UV-A light by activating p53-dependent apoptosis. Targeting the DJ-1-Nrf2 axis may provide a potential therapeutic approach for enhancing antioxidant defense in corneal endothelial disorders.},
	keywords = {Animals, Antioxidants, Apoptosis, Cells, Cultured, Down-Regulation, Endothelial Cells, Endothelium, Corneal, Humans, Intracellular Signaling Peptides and Proteins, Mice, Mice, Knockout, NF-E2-Related Factor 2, Oncogene Proteins, Oxidative Stress, Protein Deglycase DJ-1, Reactive Oxygen Species, Ultraviolet Rays},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14580},
	author = {Liu, Cailing and Chen, Yuming and Kochevar, Irene E and Jurkunas, Ula V}
}
@article {1664949,
	title = {Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization},
	journal = {Aging (Albany NY)},
	volume = {15},
	number = {1},
	year = {2023},
	month = {2023 Jan 10},
	pages = {37-52},
	abstract = {Choroidal neovascularization (CNV) causes acute vision loss in neovascular age-related macular degeneration (AMD). Genetic variations of the nuclear receptor RAR-related orphan receptor alpha (RORα) have been linked with neovascular AMD, yet its specific role in pathological CNV development is not entirely clear. In this study, we showed that Rora was highly expressed in the mouse choroid compared with the retina, and genetic loss of RORα in Staggerer mice (Rorasg/sg) led to increased expression levels of Vegfr2 and Tnfa in the choroid and retinal pigment epithelium (RPE) complex. In a mouse model of laser-induced CNV, RORα expression was highly increased in the choroidal/RPE complex post-laser, and loss of RORα in Rorasg/sg eyes significantly worsened CNV with increased lesion size and vascular leakage, associated with increased levels of VEGFR2 and TNFα proteins. Pharmacological inhibition of RORα also worsened CNV. In addition, both genetic deficiency and inhibition of RORα substantially increased vascular growth in isolated mouse choroidal explants ex vivo. RORα inhibition also promoted angiogenic function of human choroidal endothelial cell culture. Together, our results suggest that RORα negatively regulates pathological CNV development in part by modulating angiogenic response of the choroidal endothelium and inflammatory environment in the choroid/RPE complex.},
	keywords = {Angiogenesis Inhibitors, Animals, Choroidal Neovascularization, Disease Models, Animal, Humans, Lasers, Mice, Mice, Inbred C57BL, Vascular Endothelial Growth Factor A, Visual Acuity, Wet Macular Degeneration},
	issn = {1945-4589},
	doi = {10.18632/aging.204480},
	author = {Liu, Chi-Hsiu and Yemanyi, Felix and Bora, Kiran and Kushwah, Neetu and Blomfield, Alexandra K and Kamenecka, Theodore M and SanGiovanni, John Paul and Sun, Ye and Solt, Laura A and Chen, Jing}
}
@article {541316,
	title = {A Man with Paraneoplastic Retinopathy plus Small Fiber Polyneuropathy Associated with Waldenstr{\"o}m Macroglobulinemia (Lymphoplasmacytic Lymphoma): Insights into Mechanisms},
	journal = {Ocul Immunol Inflamm},
	volume = {23},
	number = {5},
	year = {2015},
	month = {2015},
	pages = {405-9},
	abstract = {PURPOSE: To report a well-characterized Waldenstr{\"o}m{\textquoteright}s macroglobulinemia (WM) case that provides insight into the mechanisms of two paraneoplastic complications -- cancer-associated retinopathy (CAR) and small fiber polyneuropathy (SFPN).

METHODS: Retrospective medical chart review.

RESULTS: A 58-year old man with WM developed vision loss and bilateral lower extremity pain. CAR was diagnosed by history, a depressed electroretinogram (ERG) and positive anti-retinal antibodies. SFPN diagnosis was based on abnormal autonomic nerve function testing and a distal-leg skin biopsy that demonstrated absent epidermal small-fiber innervation, IgM and complement deposition and microvasculopathy. Plasma exchange (PLEX) led to dramatic pain relief and subjective improvement in eye symptoms along with improvement of some ERG parameters. Repeat skin biopsy after treatment showed less microvascular abnormalities and decreased complement deposition.

CONCLUSIONS: The concurrence of CAR and SFPN in this patient suggest that both were complications of WM and their common response to PLEX suggests co-mediation by humoral factors that accessed target antigens through IgM-triggered, complement-mediated vascular damage.},
	keywords = {Diagnosis, Differential, Electroretinography, Fluorescein Angiography, Fundus Oculi, Humans, Male, Middle Aged, Nerve Fibers, Paraneoplastic Syndromes, Periodicity, Polyneuropathies, Retina, Retinal Diseases, Retrospective Studies, Skin, Waldenstrom Macroglobulinemia},
	issn = {1744-5078},
	doi = {10.3109/09273948.2014.884599},
	author = {Liu, Yingna and Magro, Cynthia and Loewenstein, John I and Makar, Robert S and Stowell, Christopher P and Dzik, Walter H and Hochberg, Ephraim P and Oaklander, Anne Louise and Sobrin, Lucia}
}
@article {913496,
	title = {Retinal expression of small non-coding RNAs in a murine model of proliferative retinopathy.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016},
	pages = {33947},
	abstract = {Ocular neovascularization is a leading cause of blindness in proliferative retinopathy. Small non-coding RNAs (sncRNAs) play critical roles in both vascular and neuronal development of the retina through post-transcriptional regulation of target gene expression. To identify the function and therapeutic potential of sncRNAs in retinopathy, we assessed the expression profile of retinal sncRNAs in a mouse model of oxygen-induced retinopathy (OIR) with pathologic proliferation of neovessels. Approximately 2\% of all analyzed sncRNAs were significantly altered in OIR retinas compared with normoxic controls. Twenty three microRNAs with substantial up- or down-regulation were identified, including miR-351, -762, -210, 145, -155, -129-5p, -150, -203, and -375, which were further analyzed for their potential target genes in angiogenic, hypoxic, and immune response-related pathways. In addition, nineteen small nucleolar RNAs also revealed differential expression in OIR retinas compared with control retinas. A decrease of overall microRNA expression in OIR retinas was consistent with reduced microRNA processing enzyme Dicer, and increased expression of Alu element in OIR. Together, our findings elucidated a group of differentially expressed sncRNAs in a murine model of proliferative retinopathy. These sncRNAs may exert critical post-transcriptional regulatory roles in regulating pathological neovascularization in eye diseases.},
	issn = {2045-2322},
	doi = {10.1038/srep33947},
	author = {Liu, Chi-Hsiu and Wang, Zhongxiao and Sun, Ye and SanGiovanni, John Paul and Chen, Jing}
}
@article {1460365,
	title = {Blockade of MDM2 with inactive Cas9 prevents epithelial to mesenchymal transition in retinal pigment epithelial cells},
	journal = {Lab Invest},
	volume = {99},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {1874-1886},
	abstract = {Epithelial to mesenchymal transition (EMT) plays an important role in the pathogenesis of proliferative vitreoretinopathy (PVR). We aimed to demonstrate the role of mouse double minute 2 (MDM2) in transforming growth factor-beta 2 (TGF-β2)-induced EMT in human retinal pigment epithelial cells (RPEs). Immunofluorescence was used to assess MDM2 expression in epiretinal membranes (ERMs) from patients with PVR. A single guide (sg)RNA targeting the second promoter of MDM2 was cloned into a mutant lentiviral Clustered Regularly Interspaced Short Palindromic Repeats (lentiCRISPR) v2 (D10A and H840A) vector for expressing nuclease dead Cas9 (dCas9)/MDM2-sgRNA in RPEs. In addition, MDM2-sgRNA was also cloned into a pLV-sgRNA-dCas9-Kruppel associated box (KRAB) vector for expressing dCas9 fused with a transcriptional repressor KRAB/MDM2-sgRNA. TGF-β2-induced expression of MDM2 and EMT biomarkers were assessed by quantitative polymerase chain reaction (q-PCR), western blot, or immunofluorescence. Wound-healing and proliferation assays were used to evaluate the role of MDM2 in TGF-β2-induced responses in RPEs. As a result, we found that MDM2 was expressed obviously in ERMs, and that TGF-β2-induced expression of MDM2 and EMT biomarkers Fibronectin, N-cadherin and Vimentin in RPEs. Importantly, we discovered that the dCas9/MDM2-sgRNA blocked TGF-β2-induced expression of MDM2 and the EMT biomarkers without affecting their basal expression, whereas the dCas9-KRAB/MDM2-sgRNA suppressed basal MDM2 expression in RPEs. These cells could not be maintained continuously because their viability was greatly reduced. Next, we found that Nutlin-3, a small molecule blocking the interaction of MDM2 with p53, inhibited TGF-β2-induced expression of Fibronectin and N-cadherin but not Vimentin in RPEs, indicating that MDM2 functions in both p53-dependent and -independent pathways. Finally, our experimental data demonstrated that dCas9/MDM2-sgRNA suppressed TGF-β2-dependent cell proliferation and migration without disturbing the unstimulated basal activity. In conclusion, the CRISPR/dCas9 capability for blocking TGF-β2-induced expression of MDM2 and EMT biomarkers can be exploited for a therapeutic approach to PVR.},
	issn = {1530-0307},
	doi = {10.1038/s41374-019-0307-9},
	author = {Liu, Bing and Song, Jingyuan and Han, Haote and Hu, Zhengping and Chen, Na and Cui, Jing and Matsubara, Joanne Aiko and Zhong, Jingxiang and Lei, Hetian}
}
@article {742981,
	title = {UV-A Irradiation Activates Nrf2-Regulated Antioxidant Defense and Induces p53/Caspase3-Dependent Apoptosis in Corneal Endothelial Cells.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {4},
	year = {2016},
	month = {2016 Apr 1},
	pages = {2319-27},
	abstract = {PURPOSE: To examine whether Nrf2-regulated antioxidant defense and p53 are activated in human corneal endothelial cells (CEnCs) by environmental levels of ultraviolet A (UV-A), a known stimulator of oxidative stress. METHODS: Immortalized human CEnCs (HCEnCi) were exposed to UV-A fluences of 2.5, 5, 10, or 25 J/cm2, then allowed to recover for 3 to 24 hours. Control HCEnCi did not receive UV-A. Reactive oxygen species (ROS) were measured using H2DCFDA. Cell cytotoxicity was evaluated by lactate dehydrogenase (LDH) release. Levels of Nrf2, HO-1, NQO-1, p53, and caspase3 were detected by immunnoblotting or real-time PCR. Activated caspase3 was measured by immunoblotting and a fluorescence assay. RESULTS: Exposure of HCEnCi to 5, 10, and 25 J/cm2 UV-A increased ROS levels compared with controls. Nrf2, HO-1, and NQO-1 mRNA increased 1.7- to 3.2-fold at 3 and 6 hours after irradiation with 2.5 and 5 J/cm2 UV-A. At 6 hours post irradiation, UV-A (5 J/cm2) enhanced nuclear Nrf2 translocation. At 24 hours post treatment, UV-A (5, 10, and 25 J/cm2) produced a 1.8- to 2.8-fold increase in phospho-p53 and a 2.6- to 6.0-fold increase in activated caspase3 compared with controls, resulting in 20\% to 42\% cell death. CONCLUSIONS: Lower fluences of UV-A induce Nrf2-regulated antioxidant defense and higher fluences activate p53 and caspase3, indicating that even near-environmental levels of UV-A may affect normal CEnCs. This data suggest that UV-A may especially damage cells deficient in antioxidant defense, and thus may be involved in the etiology of Fuchs{\textquoteright} endothelial corneal dystrophy (FECD).},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-19097},
	author = {Liu, Cailing and Vojnovic, Dijana and Kochevar, Irene E and Jurkunas, Ula V}
}
@article {1439854,
	title = {A Meta-analysis of Retinal Cytoarchitectural Abnormalities in Schizophrenia and Bipolar Disorder},
	journal = {Schizophr Bull},
	volume = {46},
	number = {1},
	year = {2020},
	month = {2020 Jan 04},
	pages = {43-53},
	abstract = {BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are characterized by reductions in gray matter and white matter. Limitations in brain imaging have led researchers to use optical coherence tomography (OCT) to explore retinal imaging biomarkers of brain pathology. We examine the retinal layers that may be associated with SZ or BD. METHODS: Articles identified using PubMed, Web of Science, Cochrane Database. Twelve studies met inclusion for acutely/chronically ill patients. We used fixed or random effects meta-analysis for probands (SZ and BD), SZ or BD eyes vs healthy control (HC) eyes. We adjusted for sources of bias, cross-validated results, and report standardized mean differences (SMD). Statistical analysis performed using meta package in R. RESULTS: Data from 820 proband eyes (SZ = 541, BD = 279) and 904 HC eyes were suitable for meta-analysis. The peripapillary retinal nerve fiber layer (RNFL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 12, SMD = -0.74, -0.51, -1.06, respectively). RNFL thinning was greatest in the nasal, temporal, and superior regions. The combined peripapillary ganglion cell layer and inner plexiform layer (GCL-IPL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 4, SMD = -0.39, -0.44, -0.28, respectively). No statistically significant differences were identified in other retinal or choroidal regions. Clinical variables were unrelated to the RNFL or GCL-IPL thickness by meta-regression. CONCLUSION: The observed retinal layer thinning is consistent with the classic gray- and white-matter atrophy observed on neuroimaging in SZ and BD patients. OCT may be a useful biomarker tool in studying the neurobiology of psychosis.},
	issn = {1745-1701},
	doi = {10.1093/schbul/sbz029},
	author = {Lizano, Paulo and Bannai, Deepthi and Lutz, Olivia and Kim, Leo A and Miller, John and Keshavan, Matcheri}
}
@article {1302169,
	title = {Association of Low Vitamin D Levels with Noninfectious Uveitis and Scleritis},
	journal = {Ocul Immunol Inflamm},
	year = {2018},
	month = {2018 Feb 23},
	pages = {1-8},
	abstract = {PURPOSE: To determine whether an association between Vitamin D and noninfectious ocular inflammation exists. METHODS: Retrospective case-control study with 765 patients (333 uveitis cases, 103 scleritis cases, 329 controls). Logistic regression models examined the relationship between hypovitaminosis D and ocular inflammation. RESULTS: The odds of having uveitis were 1.92 times higher for patients with hypovitaminosis D compared to patients with normal Vitamin D levels in the multivariate analysis [odds ratio (OR)\&nbsp;=\&nbsp;1.92, 95\% Confidence Interval (CI)\&nbsp;=\&nbsp;1.36-2.72, p\&nbsp;=\&nbsp;2.32\&nbsp;{\texttimes}\&nbsp;10]. A secondary analysis demonstrated that the odds of developing uveitis or scleritis were 5\% lower and 4\% lower, respectively, for every unit increase in Vitamin D level (uveitis: OR\&nbsp;=\&nbsp;0.95, 95\% CI\&nbsp;=\&nbsp;0.94-0.97, p\&nbsp;=\&nbsp;9.87\&nbsp;{\texttimes}\&nbsp;10; scleritis: OR\&nbsp;=\&nbsp;0.96, 95\% CI\&nbsp;=\&nbsp;0.93-0.99, p\&nbsp;=\&nbsp;0.009). CONCLUSION: Hypovitaminosis D was associated with increased risk of ocular inflammation in this retrospective study.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2018.1434208},
	author = {Llop, Stephanie M and Davoudi, Samaneh and Stanwyck, Lynn K and Sathe, Shaleen and Tom, Lisa and Ahmadi, Tina and Grotting, Lindsay and Papaliodis, George N and Sobrin, Lucia}
}
@article {1364509,
	title = {Delayed interval of involvement of the second eye in a male patient with bilateral Chandler{\textquoteright}s syndrome},
	journal = {Br J Ophthalmol},
	volume = {96},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {134-5, 146-7},
	keywords = {Adult, Corneal Endothelial Cell Loss, Disease Progression, Eye, Glaucoma, Angle-Closure, Humans, Iridocorneal Endothelial Syndrome, Male, Trabeculectomy},
	issn = {1468-2079},
	doi = {10.1136/bjo.2009.177931},
	author = {Lobo, A-M and Rhee, D. J.}
}
@article {1302185,
	title = {Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {3},
	year = {2018},
	month = {2018 Mar 01},
	pages = {271-277},
	abstract = {Importance: Mice with oxygen-induced retinopathy fed matched diets except for ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs ω-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of ω-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation.

Objective: To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating ω-3 and ω-6 LC-PUFAs.

Design, Setting, and Participants: This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospital in G{\"o}teborg, Sweden.

Main Outcomes and Measures: Serum phospholipid fatty acids were transmethylated and measured by gas chromatography-mass spectrometry. Mann-Whitney test, logistic regression Spearman rank correlation, and receiver operating characteristic curve analysis were used to compare differences between infants with no ROP and infants who developed ROP.

Results: Serum levels from 78 infants (43 male [55\%]; mean [SD] GA, 25.5 [1.4] weeks) with a known ROP outcome were evaluated. Lower area under the curve (AUC) of arachidonic acid (AA) (20:4 ω-6) was seen in infants with a later diagnosis of ROP compared with infants with no ROP in the first month of life (mean, 34.05 [95\% CI, 32.10-36.00] vs 37.15 [95\% CI, 34.85-39.46]; P ,
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.6658},
	author = {L{\"o}fqvist, Chatarina A and Najm, Svetlana and Hellgren, Gunnel and Engstr{\"o}m, Eva and S{\"a}vman, Karin and Nilsson, Anders K and Andersson, Mats X and H{\r a}rd, Anna-Lena and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1589759,
	title = {Cis-regulatory dissection of cone development reveals a broad role for Otx2 and Oc transcription factors},
	journal = {Development},
	volume = {148},
	number = {9},
	year = {2021},
	month = {2021 May 01},
	abstract = {The vertebrate retina is generated by retinal progenitor cells (RPCs), which produce \&gt;100 cell types. Although some RPCs produce many cell types, other RPCs produce restricted types of daughter cells, such as a cone photoreceptor and a horizontal cell (HC). We used genome-wide assays of chromatin structure to compare the profiles of a restricted cone/HC RPC and those of other RPCs in chicks. These data nominated regions of regulatory activity, which were tested in tissue, leading to the identification of many cis-regulatory modules (CRMs) active in cone/HC RPCs and developing cones. Two transcription factors, Otx2 and Oc1, were found to bind to many of these CRMs, including those near genes important for cone development and function, and their binding sites were required for activity. We also found that Otx2 has a predicted autoregulatory CRM. These results suggest that Otx2, Oc1 and possibly other Onecut proteins have a broad role in coordinating cone development and function. The many newly discovered CRMs for cones are potentially useful reagents for gene therapy of cone diseases.},
	issn = {1477-9129},
	doi = {10.1242/dev.198549},
	author = {Lonfat, Nicolas and Wang, Su and Lee, Changhee and Garcia, Mauricio and Choi, Jiho and Park, Peter J and Cepko, Connie}
}
@article {1078781,
	title = {Epigenomics of Retinal Development in Mice and Humans},
	journal = {Neuron},
	volume = {94},
	number = {3},
	year = {2017},
	month = {2017 May 03},
	pages = {420-423},
	abstract = {In this issue of Neuron, Aldiri et\&nbsp;al. (2017) present an analysis of epigenetic changes during retinal development, and use these data to probe reprogramming of retinal iPSC cells, as well as the origin of retinoblastoma cells.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2017.04.029},
	author = {Lonfat, Nicolas and Cepko, Connie}
}
@article {1593831,
	title = {Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM)},
	journal = {Blood Cancer J},
	volume = {11},
	number = {5},
	year = {2021},
	month = {2021 May 26},
	pages = {103},
	abstract = {Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit-risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.},
	issn = {2044-5385},
	doi = {10.1038/s41408-021-00494-4},
	author = {Lonial, Sagar and Nooka, Ajay K and Thulasi, Praneetha and Badros, Ashraf Z and Jeng, Bennie H and Callander, Natalie S and Potter, Heather A and Sborov, Douglas and Zaugg, Brian E and Popat, Rakesh and Esposti, Simona Degli and Byrne, Julie and Opalinska, Joanna and Baron, January and Piontek, Trisha and Gupta, Ira and Dana, Reza and Farooq, Asim V and Colby, Kathryn and Jakubowiak, Andrzej}
}
@article {1351163,
	title = {Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss},
	journal = {Ophthalmology},
	volume = {121},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {508-16},
	abstract = {PURPOSE: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further.

DESIGN: Case-control study.

PARTICIPANTS: We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls).

METHODS: We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 {\texttimes} 10(-4) was used to account for multiple comparisons.

MAIN OUTCOME MEASURES: Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss.

RESULTS: We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 {\texttimes} 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 {\texttimes} 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 {\texttimes} 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men.

CONCLUSIONS: CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.},
	keywords = {Aged, Case-Control Studies, Caveolin 1, Caveolin 2, Female, Genomic Structural Variation, Genotype, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Middle Aged, Polymorphism, Single Nucleotide, Sex Factors, Vision Disorders, Visual Fields},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2013.09.012},
	author = {Loomis, Stephanie J and Kang, Jae H and Weinreb, Robert N and Yaspan, Brian L and Cooke Bailey, Jessica N and Gaasterland, Douglas and Gaasterland, Terry and Lee, Richard K and Lichter, Paul R and Budenz, Donald L and Liu, Yutao and Realini, Tony and Friedman, David S and McCarty, Catherine A and Moroi, Sayoko E and Olson, Lana and Schuman, Joel S and Singh, Kuldev and Vollrath, Douglas and Wollstein, Gadi and Zack, Donald J and Brilliant, Murray and Sit, Arthur J and Christen, William G and Fingert, John and Kraft, Peter and Zhang, Kang and Allingham, R Rand and Pericak-Vance, Margaret A and Richards, Julia E and Hauser, Michael A and Haines, Jonathan L and Pasquale, Louis R and Wiggs, Janey L}
}
@article {1698411,
	title = {Resilience to autosomal dominant Alzheimer{\textquoteright}s disease in a Reelin-COLBOS heterozygous man},
	journal = {Nat Med},
	volume = {29},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {1243-1252},
	abstract = {We characterized the world{\textquoteright}s second case with ascertained extreme resilience to autosomal dominant Alzheimer{\textquoteright}s disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.},
	keywords = {Alzheimer Disease, Animals, Arthrogryposis, Female, Heterozygote, Humans, Male, Mice, Nerve Tissue Proteins, Signal Transduction},
	issn = {1546-170X},
	doi = {10.1038/s41591-023-02318-3},
	author = {Lopera, Francisco and Marino, Claudia and Chandrahas, Anita S and O{\textquoteright}Hare, Michael and Villalba-Moreno, Nelson David and Aguillon, David and Baena, Ana and Sanchez, Justin S and Vila-Castelar, Clara and Ramirez Gomez, Liliana and Chmielewska, Natalia and Oliveira, Gabriel M and Littau, Jessica Lisa and Hartmann, Kristin and Park, Kyungeun and Krasemann, Susanne and Glatzel, Markus and Schoemaker, Dorothee and Gonzalez-Buendia, Lucia and Delgado-Tirado, Santiago and Arevalo-Alquichire, Said and Saez-Torres, Kahira L and Amarnani, Dhanesh and Kim, Leo A and Mazzarino, Randall C and Gordon, Harper and Bocanegra, Yamile and Villegas, Andres and Gai, Xiaowu and Bootwalla, Moiz and Ji, Jianling and Shen, Lishuang and Kosik, Kenneth S and Su, Yi and Chen, Yinghua and Schultz, Aaron and Sperling, Reisa A and Johnson, Keith and Reiman, Eric M and Sepulveda-Falla, Diego and Arboleda-Velasquez, Joseph F and Quiroz, Yakeel T}
}
@article {1359937,
	title = {The Chemokine Receptor CXCR4 Mediates Recruitment of CD11c+ Conventional Dendritic Cells Into the Inflamed Murine Cornea},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {13},
	year = {2018},
	month = {2018 Nov 01},
	pages = {5671-5681},
	abstract = {Purpose: The cornea contains distinct populations of antigen-presenting cells (APCs), including conventional dendritic cells (cDCs). Little is known about the molecular mechanisms involved in cDCs homing and recruitment into the na{\"\i}ve and inflamed cornea. The purpose of this study was to investigate the presence of CXCR4 and its ligand CXCL12 in the murine cornea and its role in cDC migration during corneal inflammation. Methods: The expression of CXCR4 and CXCL12 in na{\"\i}ve and suture-inflamed murine corneas was assessed by whole-mount staining, flow cytometry, and quantitative PCR. The role of CXCR4 in recruitment into inflamed corneas was investigated using adoptive transfer of cDCs blocked with neutralizing antibody against CXCR4. Results: We show the chemokine receptor CXCR4 to be expressed on 51.7\% and 64.8\% of total corneal CD11c+ cDCs, equating to 98.6 {\textpm} 12.5 cells/mm2 in the peripheral and 64.7 {\textpm} 10.6 cells/mm2 in the central na{\"\i}ve cornea, respectively. Along with a 4.5-fold increase in CXCL12 expression during inflammation (P \&lt; 0.05), infiltrating cDCs also expressed CXCR4 in both the peripheral (222.6 {\textpm} 33.3 cells/mm2; P \&lt; 0.001) and central cornea (161.9 {\textpm} 23.8 cells/mm2; P = 0.001), representing a decrease to 31.0\% and 37.3\% in the cornea, respectively. Further, ex vivo blockade (390.1 {\textpm} 40.1 vs. 612.1 {\textpm} 78.3; P = 0.008) and local blockade (263.5 {\textpm} 27.1 vs. 807.5 {\textpm} 179.5, P \&lt; 0.001) with anti-CXCR4 neutralizing antibody resulted in a decrease in cDCs homing into the cornea compared with cells pretreated with isotype controls. Conclusions: Our results demonstrate that corneal CXCL12 plays a direct role in CXCR4+ cDC recruitment into the cornea. The CXCR4/CXCL12 axis is therefore a potential target to modulate corneal inflammatory responses.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-25084},
	author = {Lopez, Maria J and Seyed-Razavi, Yashar and Jamali, Arsia and Harris, Deshea L and Hamrah, Pedram}
}
@article {1062836,
	title = {An evidence-based approach to surgical teaching in ophthalmology},
	journal = {Surv Ophthalmol},
	volume = {62},
	number = {3},
	year = {2017},
	month = {2017 May - Jun},
	pages = {371-377},
	abstract = {
	An apprenticeship model has traditionally been used in procedural and surgical teaching. As the pressures of work hours and patient outcome monitoring increase, surgical teachers need a more flexible plan for teaching procedural skills. We attempt to delineate a program of preprocedural, intraprocedural, and postprocedural teaching that can be used in the field of ophthalmology to maximize a resident{\textquoteright}s skill acquisition in a constructive learning environment. We review the literature on surgical teaching from within ophthalmology as well as other surgical fields and combine this with teaching experience in an ophthalmic surgical training program to produce a collection of procedural teaching guidelines. These guidelines are structured to serve in both individual teaching settings and in curriculum design.

},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2017.01.003},
	author = {Lorch, Alice C and Kloek, Carolyn E}
}
@article {1608599,
	title = {The Prevalence of Autoimmune Diseases in Patients with Primary Open-Angle Glaucoma Undergoing Ophthalmic Surgeries},
	journal = {Ophthalmol Glaucoma},
	volume = {5},
	number = {2},
	year = {2022},
	month = {2022 Mar-Apr},
	pages = {128-136},
	abstract = {PURPOSE: To assess the prevalence of autoimmune disease (AiD) in patients with primary open-angle glaucoma (POAG) undergoing ophthalmic surgery. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: Patients with POAG undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019 to April\&nbsp;2020. METHODS: All available medical records with patient demographics, ocular, and medical conditions were reviewed. Differences in AiD prevalence were assessed and adjusted for covariates using multiple logistic regression. Additionally, a subgroup analysis comparing the POAG patients with and without AiD was performed. MAIN OUTCOME MEASURES: To assess the prevalence of AiD based on the American Autoimmune Related Diseases Association list. RESULTS: A total of 172 patients with POAG and 179 controls were included. The overall prevalence of AiD was 17.4\% in the POAG group and 10.1\% in the controls (P\&nbsp;= 0.044); 6.4\% of POAG patients and 3.4\% of controls had more than 1 AiD (P\&nbsp;= 0.18). The most prevalent AiDs in POAG group were rheumatoid arthritis (4.6\%) and psoriasis (4.1\%), which were also the most common in controls (2.8\% each). In a fully adjusted multiple logistic regression analysis accounting for steroid use, having an AiD was associated with 2.62-fold increased odds of POAG relative to controls (95\% confidence interval, 1.27-5.36, P\&nbsp;= 0.009); other risk factors for POAG derived from the analysis included age (odds ratio [OR], 1.04, P\&nbsp;= 0.006), diabetes mellitus (OR, 2.31, P\&nbsp;= 0.008), and non-White ethnicity (OR, 4.75, P \&lt; 0.001). In a case-only analysis involving the eye with worse glaucoma, there was no statistical difference in visual field mean deviation or retinal nerve fiber layer (RNFL) thickness in POAG patients with AiD (n\&nbsp;= 30) and without AiD (n\&nbsp;= 142, P \&gt; 0.13, for both). CONCLUSIONS: A higher prevalence of AiD was found in POAG patients compared with control patients undergoing ophthalmic surgery. The presence of AiD was associated with increased risk for POAG after adjusting for covariates. Additional factors may have prevented a difference in RNFL thickness in POAG patients with and without AiD. Autoimmunity should be explored further in the pathogenesis of POAG.},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.08.003},
	author = {Lorenzo, Maltish M and Devlin, Julia and Saini, Chhavi and Cho, Kin-Sang and Paschalis, Eleftherios I and Chen, Dong Feng and Silva, Rafaella Nascimento E and Chen, Sherleen H and Margeta, Milica A and Ondeck, Courtney and Sol{\'a}-Del Valle, David and Chodosh, James and Ciolino, Joseph B and Pineda, Roberto and Pasquale, Louis R and Shen, Lucy Q}
}
@article {836911,
	title = {Comparison of Peristat Online Perimetry with the Humphrey Perimetry in a Clinic-Based Setting.},
	journal = {Transl Vis Sci Technol},
	volume = {5},
	number = {4},
	year = {2016},
	month = {2016 Jul},
	pages = {4},
	abstract = {PURPOSE: We determined the receiver operating characteristic (ROC) curves for Peristat online perimetry at detecting varying degrees of glaucoma and the correlation between Peristat online perimetry and Humphrey visual field. METHODS: A prospective, comparative study of Peristat online perimetry (an achromatic static computer threshold testing program) and Humphrey visual field (HVF) 24-2 SITA standard testing was performed by 63 glaucoma patients and 30 healthy controls in random order. The number of total adjacent abnormal test points were identified for each test, and compared with Spearman correlation. Receive operating characteristic curves were generated for Peristat online perimetry detection of mild and moderate-severe glaucoma patients using contrast sensitivity thresholds of -16.7, -21.7, and -26.7 dB. RESULTS: The area under the ROC curve for glaucoma detection ranged from 0.77 to 0.81 for mild disease (mean deviation [MD], \&gt;-6 dB on HVF) and 0.85 to 0.87 for moderate to severe disease (MD, \&lt;-6 dB on HVF) depending on contrast threshold. Peristat online perimetry and Humphrey visual field abnormal points were highly correlated with Spearman rank correlations ranging from 0.55 to 0.77 (all P \&lt; 0.001). CONCLUSIONS: Peristat online perimetry exhibits a reasonable ROC curve without specialized equipment and exhibited significant correlation with the conventional 24{\textdegree} Humphrey visual field test. TRANSLATIONAL RELEVANCE: Low cost widely available internet-based visual fields may complement traditional office-based visual field testing.},
	issn = {2164-2591},
	doi = {10.1167/tvst.5.4.4},
	author = {Lowry, Eugene A and Hou, Jing and Hennein, Lauren and Chang, Robert T and Lin, Shan and Keenan, Jeremy and Wang, Sean K and Ianchulev, Sean and Pasquale, Louis R and Han, Ying}
}
@article {1789196,
	title = {Detection of Choroidal Hypoperfusion in Giant Cell Arteritis Using Swept-Source Optical Coherence Tomographic Angiography},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {4},
	year = {2023},
	month = {2023 Dec 01},
	pages = {e117-e119},
	keywords = {Angiography, Choroid, Choroid Diseases, Fluorescein Angiography, Giant Cell Arteritis, Humans, Tomography, Optical Coherence},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001485},
	author = {Lu, Edward S and Yuan, Amy and Cohen, Devon A and Katz, Raviv and Miller, John B and Gaier, Eric D}
}
@article {1490438,
	title = {Detection of retinal microvascular changes in von Hippel-Lindau disease using optical coherence tomography angiography},
	journal = {PLoS One},
	volume = {15},
	number = {2},
	year = {2020},
	month = {2020},
	pages = {e0229213},
	abstract = {PURPOSE: Von Hippel-Lindau (VHL) disease is a hereditary disorder that can lead to ophthalmic manifestations, including retinal capillary hemangioma (RCH). The diagnosis of RCH is often guided by wide-field fluorescein angiography. In some cases, optical coherence tomography angiography (OCT-A) serves as a non-invasive alternative to FA. Herein, we used OCT-A to examine the macular microvasculature in patients with VHL disease. SUBJECTS: Subjects were selected from patients with a diagnosis of VHL. The control group included eyes without retinal diagnosis from patients with an episode of unilateral retinal detachment or trauma and age <= 50 years old. METHODS: Subjects were scanned on the Optovue RTVue-XR device to acquire 3mm x 3mm OCT-A images of the superficial (SCP) and deep capillary plexus (DCP). SCP and DCP vessel density (VD) were calculated after the images were binarized. Furthermore, for subjects with RCH, each OCT-A image was divided equally into four quadrants. SCP and DCP VD of quadrants with RCH were compared to those without RCH. T-tests were performed for statistical analysis. RESULTS: 67 eyes with a history of VHL disease were included as study subjects, while 16 eyes were included as controls. Significant increases in VD were found in patients with VHL disease for both the SCP (p = 0.0441) and DCP (p = 0.0344). When comparing quadrants with associated RCH development to those without, we found no significant difference in SCP VD (p = 0.160) or DCP VD (p = 0.484). CONCLUSIONS: OCT-A can detect changes in the retinal microvasculature in the macula of patients with VHL disease. OCT-A imaging may be an additional tool for screening and early detection of patients at risk of developing ocular complications of VHL disease. Future studies should explore subtle progression on OCT-A associated with the pathogenesis and development of RCH, particularly with larger scan patterns.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0229213},
	author = {Lu, Yifan and Wang, Jay C and Zeng, Rebecca and Nagata, Tatsuo and Katz, Raviv and Mukai, Shizuo and Miller, John B}
}
@article {1748411,
	title = {Quantitative Wide-Field Swept-Source Optical Coherence Tomography Angiography and Visual Outcomes in RAO},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {2505-2513},
	abstract = {PURPOSE: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcomes and is associated with an increased risk of stroke and cardiovascular events. Wide-field swept-source OCT-A (WF SS-OCTA) can provide quick and non-invasive angiographic information with a wide field of view. Here, we looked for associations between OCT-A vascular imaging metrics and vision in RAO patients. METHODS: Patients with diagnoses of central (CRAO) or branched retinal artery occlusion (BRAO) were included. 6mm {\texttimes} 6mm Angio and 15mm {\texttimes} 15mm AngioPlex Montage OCT-A images were obtained for both eyes in each patient using Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm {\texttimes} 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Non-perfusion area (NPA) was manually measured using 15mm {\texttimes} 15mm images. A linear regression model was utilized to identify correlation between imaging metrics and vision. P-values less than 0.05 were considered as statistically significant. RESULTS: Twenty-five subjects were included. For RAO eyes, there was a statistically significant inverse correlation between retinal thickness as well as superficial capillary plexus (SCP) vessel density (VD) and vision. An inverse correlation was found between deep capillary plexus (DCP) VD and vision without statistical significance. There was a positive correlation between choroidal thickness as well as choroidal volume and vision without statistical significance. No significant correlation was found between the metrics and vision in contralateral eyes. For NPA and vision, no significant correlation was identified. CONCLUSION: This is the first study to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between retinal vascular imaging metrics and visual outcomes. The results of this study provide a basis to understand the structural changes involved in vision in RAO and may guide management of RAO and prevention of cerebral stroke and cardiovascular accidents.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S418370},
	author = {Lu, Yifan and Cui, Ying and Zhu, Ying and Lu, Edward S and Zeng, Rebecca and Garg, Itika and Katz, Raviv and Le, Rongrong and Wang, Jay C and Vavvas, Demetrios G and Husain, Deeba and Miller, Joan W and Wu, David and Miller, John B}
}
@article {1559543,
	title = {Reprogramming to recover youthful epigenetic information and restore vision},
	journal = {Nature},
	volume = {588},
	number = {7836},
	year = {2020},
	month = {2020 12},
	pages = {124-129},
	abstract = {Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity. Changes to DNA methylation patterns over time form the basis of ageing clocks, but whether older individuals retain the\&nbsp;information needed\&nbsp;to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.},
	issn = {1476-4687},
	doi = {10.1038/s41586-020-2975-4},
	author = {Lu, Yuancheng and Brommer, Benedikt and Tian, Xiao and Krishnan, Anitha and Meer, Margarita and Wang, Chen and Vera, Daniel L and Zeng, Qiurui and Yu, Doudou and Bonkowski, Michael S and Yang, Jae-Hyun and Zhou, Songlin and Hoffmann, Emma M and Karg, Margarete M and Schultz, Michael B and Kane, Alice E and Davidsohn, Noah and Korobkina, Ekaterina and Chwalek, Karolina and Rajman, Luis A and Church, George M and Hochedlinger, Konrad and Gladyshev, Vadim N. and Horvath, Steve and Levine, Morgan E and Gregory-Ksander, Meredith S and Ksander, Bruce R and He, Zhigang and Sinclair, David A}
}
@article {1698301,
	title = {Perceived change in age after functional upper blepharoplasty},
	journal = {Orbit},
	year = {2023},
	month = {2023 May 24},
	pages = {1-3},
	abstract = {PURPOSE: To evaluate the perceived age of patients before and after functional upper blepharoplasty. METHODS: Retrospective chart review of patients who underwent upper blepharoplasty by a single surgeon at an academic center. The inclusion criterion was having external photographs before and after blepharoplasty. Exclusion criteria included any other concurrent eyelid or facial surgery. Primary endpoint: perceived change in age after surgery as judged by the American Society of Ophthalmic Plastic \&amp; Reconstructive Surgery (ASOPRS) surgeons. RESULTS: Sixty-seven patients (14 men, 53 women) were included. Mean pre-operative age was 66.9 years (range 37.8-89.4) and mean post-operative age was 67.4 years (range 38.6-89). The mean perceived age pre-operatively was 68.9 years, and the mean perceived age post-operatively was 67.1 years, a change of 1.8 years (p = 0.0001 by two-tailed paired T-test). Inter-rater reliability of the observers was measured by intraclass correlation coefficient of 0.77 for pre-operative and 0.75 for post-operative photos. The decreased perceived age was 1.9 years for women, 1.4 years for men, 0.3 years for Asians, 1.2 years for Hispanics, and 2.1 years for whites. DISCUSSION: Functional upper blepharoplasty by an experienced ASOPRS surgeon was shown to reduce the perceived age of a patient by an average of 1.8 years.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2023.2214940},
	author = {Lu, Jonathan E and Wolkow, Natalie and Lee, N Grace and Lefebvre, Daniel R and Freitag, Suzanne K and Yoon, Michael K}
}
@article {1748416,
	title = {New keratoconus staging system based on OCT},
	journal = {J Cataract Refract Surg},
	volume = {49},
	number = {11},
	year = {2023},
	month = {2023 Nov 01},
	pages = {1098-1105},
	abstract = {PURPOSE: To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems. SETTING: Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGNS: Retrospective case-control study. METHODS: Scheimpflug tomography, air-puff tonometry, and SD-OCT were performed on 236 normal and 331 KC eyes. All SD-OCT-derived parameters of the corneal epithelium and stroma were evaluated based on their receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity to discriminate between normal and KC eyes. The best performing parameters were subsequently used to create an OCT-based staging system, which was compared with existing tomographic and biomechanical staging systems. RESULTS: 236 eyes from 236 normal patients and 331 eyes from 331 KC patients of different stages were included. The highest ranked AUC ROC SD-OCT parameters, derived from stroma and epithelium, were stroma overall minimum thickness (ST: AUC 0.836, sensitivity 90\%, specificity 67\%) and epithelium overall SD (EP: AUC 0.835, sensitivity 75\%, specificity 78\%). A numerical SD-OCT staging system called STEP including 2 parameters-"ST" and "EP"-with 5 stages was proposed. CONCLUSIONS: The new SD-OCT-based KC staging system is the first to take the epithelium with its sublayer stroma information into account, showing a strong agreement to the existing staging systems. This system could be incorporated into daily practice, potentially leading to an overall improvement in KC treatment and follow-up management.},
	keywords = {Case-Control Studies, Cornea, Corneal Topography, Epithelium, Corneal, Humans, Keratoconus, Retrospective Studies, ROC Curve, Tomography, Optical Coherence},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000001276},
	author = {Lu, Nan-Ji and Hafezi, Farhad and Koppen, Carina and Ali{\'o} Del Barrio, Jorge L and Aslanides, Ioannis M and Awwad, Shady T and N{\'\i} Dhubhghaill, Sorcha and Pineda, Roberto and Torres-Netto, Emilio A and Wang, Lin and Chen, Shi-Hao and Cui, Le-Le and Rozema, Jos J}
}
@article {1782391,
	title = {Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	year = {2023},
	month = {2023 Nov 14},
	abstract = {PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth{\textquoteright}s bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth{\textquoteright}s bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95\% confidence interval [CI]:5.3-30.7, P\&lt;0.001) and BCVA (OR=5.8, 95\%CI:1.2-28.8, P\&lt;0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06290-z},
	author = {Lu, Edward S and Cui, Ying and Le, Rongrong and Zhu, Ying and Wang, Jay C and La{\'\i}ns, In{\^e}s and Katz, Raviv and Lu, Yifan and Zeng, Rebecca and Garg, Itika and Wu, David M and Husain, Deeba and Kim, Leo A and Miller, John B}
}
@article {1532347,
	title = {A quantitative comparison of four optical coherence tomography angiography devices in healthy eyes},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {259},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {1493-1501},
	abstract = {PURPOSE: Optical coherence tomography angiography (OCT-A) is a novel imaging modality for the diagnosis of chorioretinal diseases. A number of FDA-approved OCT-A devices are currently commercially available, each with unique algorithms and scanning protocols. Although several published studies have compared different combinations of OCT-A machines, there is a lack of agreement on the consistency of measurements across OCT-A devices. Therefore, we conducted a prospective quantitative comparison of four available OCT-A platforms. METHODS: Subjects were scanned on four devices: Optovue RTVue-XR, Heidelberg Spectralis OCT2 module, Zeiss Plex Elite 9000 Swept-Source OCT, and Topcon DRI-OCT Triton Swept-Source OCT. 3 mm {\texttimes} 3 mm images were utilized for analysis. Foveal avascular zone (FAZ) area was separately and independently measured by two investigators. Fractal dimension (FD), superficial capillary plexus (SCP), and deep capillary plexus (DCP) vessel densities (VD) were calculated from binarized images using the Fiji image processing software. SCP and DCP VD were further calculated after images were skeletonized. Repeated measures ANOVA, post hoc tests, and interclass correlation coefficient (ICC) were performed for statistical analysis. RESULTS: Sixteen healthy eyes from sixteen patients were scanned on the four devices. Images of five eyes from the Triton device were excluded due to poor image quality; thus, the authors performed two sets comparisons, one with and one without the Triton machine. FAZ area showed no significant difference across devices with an ICC of \&gt; 95\%. However, there were statistically significant differences for SCP and DCP VD both before and after skeletonization (p \&lt; 0.05). Fractal analysis revealed no significant difference of FD at the SCP; however, a statistically significant difference was found for FD at the DCP layer (p \&lt; 0.05). CONCLUSIONS: The results showed that FAZ measurements were consistent across all four devices, while significant differences in VD and FD measurements existed. Therefore, we suggest that for both clinical follow-up and research studies, FAZ area is a useful parameter for OCT-A image analysis when measurements are made on different machines, while VD and FD show significant variability when measured across devices.},
	issn = {1435-702X},
	doi = {10.1007/s00417-020-04945-9},
	author = {Lu, Yifan and Wang, Jay C and Cui, Ying and Zhu, Ying and Zeng, Rebecca and Lu, Edward S and Katz, Raviv and Husain, Deeba and Vavvas, Demetrios G and Kim, Leo A and Miller, Joan W and Miller, John B}
}
@article {1664990,
	title = {The Role of Steroids for Pediatric Orbital Cellulitis - Review of the Controversy},
	journal = {Semin Ophthalmol},
	year = {2023},
	month = {2023 Jan 22},
	pages = {1-4},
	abstract = {Orbital cellulitis in the pediatric population is treated primarily with antibiotic therapy. This leaves the inflammatory component unchecked. Corticosteroid therapy has been used to accelerate recovery and decrease the long-term morbidity in other infectious conditions. Its use has also been proposed for pediatric orbital cellulitis. The aim of this manuscript is to conduct a literature review to summarize existing evidence and understand ongoing controversies. Overall, prior investigations on corticosteroid therapy for pediatric orbital cellulitis are limited by their study design and sample sizes. One of the most discussed potential benefits is that adjuvant steroid therapy for pediatric orbital cellulitis is associated with shorter hospitalization without major infectious complications. However, decreased hospitalization length is an imperfect metric, especially without standardized criteria for hospital discharge. Future studies are warranted to better guide the use of adjuvant steroid therapy and to optimize its potential in the management of pediatric orbital cellulitis.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2168487},
	author = {Lu, Jonathan E and Yoon, Michael K}
}
@article {1559553,
	title = {Detection of neovascularisation in the vitreoretinal interface slab using widefield swept-source optical coherence tomography angiography in diabetic retinopathy},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {4},
	year = {2022},
	month = {2022 Apr},
	pages = {534-539},
	abstract = {AIMS: To compare the efficacy of diabetic retinal neovascularisation (NV) detection using the widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vitreoretinal interface (VRI) Angio slab and SS-OCT VRI Structure slab. METHODS: A prospective, observational study was performed at Massachusetts Eye and Ear from January 2019 to June 2020. Patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy and patients with diabetes but without diabetic retinopathy were included. All patients were imaged with WF SS-OCTA using the 12{\texttimes}12 mm Angio scan protocol centred on the fovea and optic disc. The en-face SS-OCTA VRI Angio slab and SS-OCT VRI Structure slab were evaluated for the presence or absence of NV. SS-OCTA B-scan was used to classify NV according to cross-sectional morphology (forward, tabletop or flat). All statistical analyses were performed using SPSS V.26.0. RESULTS: One hundred and forty-two eyes of 89 participants were included in the study. VRI Angio detected NV at higher rates compared with VRI Structure (p\&lt;0.05). Combining VRI Angio and Structure improved detection rates compared with VRI Angio alone (p\&lt;0.05). Due to segmentation errors of the internal limiting membrane, NV with flat morphological classification had lower rates of detection on VRI Angio compared with NV with forward and tabletop morphology (p\&lt;0.05). CONCLUSIONS: WF SS-OCTA 12{\texttimes}12 mm VRI Angio and SS-OCT VRI Structure imaging centred on the fovea and optic disc detected NV with high sensitivity and low false positives. The VRI slab may be useful to diagnose and monitor PDR in clinical practice.},
	keywords = {Cross-Sectional Studies, Diabetes Mellitus, Diabetic Retinopathy, Fluorescein Angiography, Humans, Prospective Studies, Retinal Vessels, Tomography, Optical Coherence},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-317983},
	author = {Lu, Edward S and Cui, Ying and Le, Rongrong and Zhu, Ying and Wang, Jay C and La{\'\i}ns, In{\^e}s and Katz, Raviv and Lu, Yifan and Zeng, Rebecca and Garg, Itika and Wu, David M and Eliott, Dean and Vavvas, Demetrios G and Husain, Deeba and Miller, Joan W and Kim, Leo A and Miller, John B}
}
@article {1460374,
	title = {Considering Same-Day Access vs Emergency Department Ophthalmic Visits in Ophthalmology Trainee Education},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Aug 01},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.2939},
	author = {Lu, Yifan and Armstrong, Grayson W and Lorch, Alice}
}
@article {1655723,
	title = {Gene therapy with a synthetic adeno-associated viral vector improves audiovestibular phenotypes in Pjvk-mutant mice},
	journal = {JCI Insight},
	volume = {7},
	number = {20},
	year = {2022},
	month = {2022 Oct 24},
	abstract = {Recessive PJVK mutations that cause a deficiency of pejvakin, a protein expressed in both sensory hair cells and first-order neurons of the inner ear, are an important cause of hereditary hearing impairment. Patients with PJVK mutations garner limited benefits from cochlear implantation; thus, alternative biological therapies may be required to address this clinical difficulty. The synthetic adeno-associated viral vector Anc80L65, with its wide tropism and high transduction efficiency in various inner ear cells, may provide a solution. We delivered the PJVK transgene to the inner ear of Pjvk mutant mice using the synthetic Anc80L65 vector. We observed robust exogenous pejvakin expression in the hair cells and neurons of the cochlea and vestibular organs. Subsequent morphologic and audiologic studies demonstrated significant restoration of spiral ganglion neuron density and hair cells in the cochlea, along with partial recovery of sensorineural hearing impairment. In addition, we observed a recovery of vestibular ganglion neurons and balance function to WT levels. Our study demonstrates the utility of Anc80L65-mediated gene delivery in Pjvk mutant mice and provides insights into the potential of gene therapy for PJVK-related inner ear deficits.},
	keywords = {Animals, Cochlea, Genetic Therapy, Hair Cells, Auditory, Hearing Loss, Sensorineural, Mice, Phenotype, Proteins},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.152941},
	author = {Lu, Ying-Chang and Tsai, Yi-Hsiu and Chan, Yen-Huei and Hu, Chin-Ju and Huang, Chun-Ying and Xiao, Ru and Hsu, Chuan-Jen and Vandenberghe, Luk H and Wu, Chen-Chi and Cheng, Yen-Fu}
}
@article {1504060,
	title = {Neutrophil L-Plastin Controls Ocular Paucibacteriality and Susceptibility to Keratitis},
	journal = {Front Immunol},
	volume = {11},
	year = {2020},
	month = {2020},
	pages = {547},
	abstract = {Why ocular mucosa is paucibacterial is unknown. Many different mechanisms have been suggested but the comprehensive experimental studies are sparse. We found that a deficiency in L-plastin (LCP1), an actin bundling protein, resulted in an ocular commensal overgrowth, characterized with increased presence of conjunctival spp. The commensal overgrowth correlated with susceptibility to -induced keratitis. L-plastin knock-out (KO) mice displayed elevated bacterial burden in the -infected corneas, altered inflammatory responses, and compromised bactericidal activity. Mice with ablation of LPL under the LysM Cre ( ) and S100A8 Cre ( ) promoters had a similar phenotype to the LPL KOs mice. In contrast, infected mice did not display elevated susceptibility to infection, implicating the myeloid L-plastin-sufficient cells (e.g., macrophages and neutrophils) in maintaining ocular homeostasis. Mechanistically, the elevated commensal burden and the susceptibility to infection were linked to defects in neutrophil frequencies at steady state and during infection and compromised bactericidal activities upon priming. Macrophage exposure to commensal organisms primed neutrophil responses to , augmenting PMN bactericidal capacity in an L-plastin dependent manner. Cumulatively, our data highlight the importance of neutrophils in controlling ocular paucibacteriality, reveal molecular and cellular events involved in the process, and suggest a link between commensal exposure and resistance to infection.},
	issn = {1664-3224},
	doi = {10.3389/fimmu.2020.00547},
	author = {Lu, Xiaoxiao and Kugadas, Abirami and Smith-Page, Kirsten and Lamb, Jeffrey and Lin, Tiffany and Ru, Yusha and Morley, Sharon Celeste and Fichorova, Raina and Mittal, Sharad K and Chauhan, Sunil K and Littleton, Sejiro and Saban, Daniel and Gadjeva, Mihaela}
}
@article {1498254,
	title = {Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese},
	journal = {Clin Exp Ophthalmol},
	volume = {48},
	number = {5},
	year = {2020},
	month = {2020 Jul},
	pages = {658-665},
	abstract = {BACKGROUND: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. METHODS: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis. RESULTS: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (P = .0019, OR = 4.55, I = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (P = .81, OR = 1.05; I = 64\%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P \&gt; .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects. CONCLUSIONS: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.},
	issn = {1442-9071},
	doi = {10.1111/ceo.13744},
	author = {Lu, Shi Yao and Rong, Shi Song and Wu, Zhenggen and Huang, Chukai and Matsushita, Kenji and Ng, Tsz Kin and Leung, Christopher K S and Kawashima, Rumi and Usui, Shinichi and Tam, Pancy O S and Tsujikawa, Motokazu and Young, Alvin L and Zhang, Mingzhi and Wiggs, Janey L and Nishida, Kohji and Tham, Clement C and Pang, Chi Pui and Chen, Li Jia}
}
@article {1364510,
	title = {Retinal laser burn-induced neuropathy leads to substance P-dependent loss of ocular immune privilege},
	journal = {J Immunol},
	volume = {189},
	number = {3},
	year = {2012},
	month = {2012 Aug 01},
	pages = {1237-42},
	abstract = {Inflammation in the eye is tightly regulated by multiple mechanisms that together contribute to ocular immune privilege. Many studies have shown that it is very difficult to abrogate the immune privileged mechanism called anterior chamber-associated immune deviation (ACAID). Previously, we showed that retinal laser burn (RLB) to one eye abrogated immune privilege (ACAID) bilaterally for an extended period of time. In an effort to explain the inflammation in the nonburned eye, we postulated that neuronal signals initiated inflammation in the contralateral eye. In this study, we test the role of substance P, a neuroinflamatory peptide, in RLB-induced loss of ACAID. Histological examination of the retina with and without RLB revealed an increase of the substance P-inducible neurokinin 1 receptor (NK1-R) in the retina of first, the burned eye, and then the contralateral eye. Specific antagonists for NK1-R, given locally with Ag within 24 h, but not 3, 5, or 7 d post-RLB treatment, prevented the bilateral loss of ACAID. Substance P knockout (KO) mice retained their ability to develop ACAID post-RLB. These data support the postulate that substance P transmits early inflammatory signals from the RLB eye to the contralateral eye to induce changes to ocular immune privilege and has a central role in the bilateral loss of ACAID. The possibility is raised that blocking of the substance P pathway with NK1-R antagonists postocular trauma may prevent unwanted and perhaps extended consequences of trauma-induced inflammation in the eye.},
	keywords = {Animals, Eye Burns, Female, Homeostasis, Lasers, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Retina, Substance P},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1103264},
	author = {Lucas, Kenyatta and Karamichos, Dimitris and Mathew, Rose and Zieske, James D and Stein-Streilein, Joan}
}
@article {1688261,
	title = {Correction to: Differences in anterior peripheral pathologic myopia and macular pathologic myopia by age and gender},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {261},
	number = {9},
	year = {2023},
	month = {2023 Sep},
	pages = {2727},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06053-w},
	author = {Ludwig, Cassie A and Boucher, Nick and Saroj, Namrata and Moshfeghi, Darius M}
}
@article {1593834,
	title = {Differences in anterior peripheral pathologic myopia and macular pathologic myopia by age and gender},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {259},
	number = {11},
	year = {2021},
	month = {2021 11},
	pages = {3511-3513},
	keywords = {Fluorescein Angiography, Humans, Myopia, Myopia, Degenerative},
	issn = {1435-702X},
	doi = {10.1007/s00417-021-05217-w},
	author = {Ludwig, Cassie A and Boucher, Nick and Saroj, Namrata and Moshfeghi, Darius M}
}
@article {1573106,
	title = {Higher prevalence of fundus haemorrhages in early-screened (NEST Study) as compared to late-screened (SUNDROP Study) newborn populations},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {5},
	year = {2022},
	month = {2022 May},
	pages = {676-680},
	abstract = {BACKGROUND/AIMS: To determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4-11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages. METHODS: Retrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points. RESULTS: A total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2\% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4\% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8\%, at 2 weeks is 2.9\% and at 1 month is 0.28\%. CONCLUSION: We found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.},
	keywords = {Gestational Age, Humans, Infant, Infant, Newborn, Neonatal Screening, Observational Studies as Topic, Prevalence, Retinopathy of Prematurity, Retrospective Studies, Telemedicine, Universities},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-317908},
	author = {Ludwig, Cassie A and Jabbehdari, Sayena and Ji, Marco and Vail, Daniel and Al-Moujahed, Ahmad and Rosenblatt, Tatiana and Azad, Amee D and Veerappan, Malini and Callaway, Natalia F and Moshfeghi, Darius M}
}
@article {1559536,
	title = {Automatic Identification of Referral-Warranted Diabetic Retinopathy Using Deep Learning on Mobile Phone Images},
	journal = {Transl Vis Sci Technol},
	volume = {9},
	number = {2},
	year = {2020},
	month = {2020 12},
	pages = {60},
	abstract = {Purpose: To evaluate the performance of a deep learning algorithm in the detection of referral-warranted diabetic retinopathy (RDR) on low-resolution fundus images acquired with a smartphone and indirect ophthalmoscope lens adapter. Methods: An automated deep learning algorithm trained on 92,364 traditional fundus camera images was tested on a dataset of smartphone fundus images from 103 eyes acquired from two previously published studies. Images were extracted from live video screenshots from fundus examinations using a commercially available lens adapter and exported as a screenshot from live video clips filmed at 1080p resolution. Each image was graded twice by a board-certified ophthalmologist and compared to the output of the algorithm, which classified each image as having RDR (moderate nonproliferative DR or worse) or no RDR. Results: In spite of the presence of multiple artifacts (lens glare, lens particulates/smudging, user hands over the objective lens) and low-resolution images achieved by users of various levels of medical training, the algorithm achieved a 0.89 (95\% confidence interval [CI] 0.83-0.95) area under the curve with an 89\% sensitivity (95\% CI 81\%-100\%) and 83\% specificity (95\% CI 77\%-89\%) for detecting RDR on mobile phone acquired fundus photos. Conclusions: The fully data-driven artificial intelligence-based grading algorithm herein can be used to screen fundus photos taken from mobile devices and identify with high reliability which cases should be referred to an ophthalmologist for further evaluation and treatment. Translational Relevance: The implementation of this algorithm on a global basis could drastically reduce the rate of vision loss attributed to DR.},
	issn = {2164-2591},
	doi = {10.1167/tvst.9.2.60},
	author = {Ludwig, Cassie A and Perera, Chandrashan and Myung, David and Greven, Margaret A and Smith, Stephen J and Chang, Robert T and Leng, Theodore}
}
@article {1580483,
	title = {Ultra-Widefield Imaging for Evaluation of the Myopic Eye},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {185-190},
	abstract = {Topic : Ultra-widefield (UWF) imaging of the myopic eye. Clinical Relevance : Myopes, and particularly high and pathologic myopes, present a\&nbsp;unique challenge in fundoscopic imaging. Critical pathology is often located in the anteriormost portion of the retina, variations in posterior segment contour are difficult to capture in two-dimensional\&nbsp;images, and extremes in axial length make simply focusing imaging devices difficult. Methods: We review the evolution of modalities for ophthalmic imaging (color fundus photography [CFP], optical coherence topography [OCT], angiography, artificial intelligence [AI]) to present day UWF technology and its impact on our understanding of myopia. Results: Advances in UWF\&nbsp;technology address many of the challenges in fundoscopic imaging of myopes, providing new insights into the structure and function of the myopic eye. UWF CFP improves our ability to detect and document anterior peripheral pathology prevalent in approximately half of all high myopes. UWF OCT better captures the staphylomatous contour of the myopic eye, providing enhanced visualization of the vitreoretinal interface and progressive development of myopic traction maculopathy. UWF angiography highlights the posterior vortex veins, thin choriocapillaris, far peripheral avascularity, and peripheral retinal capillary microaneurysms more prevalent in the myopic eye. Researchers have demonstrated the ability of AI algorithms to predict refractive error, and great potential remains in the use of AI technology for the screening and prevention of myopic disease. Conclusion: We note significant progress in our ability to capture anterior pathology and improved image quality of the posterior segment of high and pathologic myopes. The next jump forward for UWF imaging will be the ability to capture a high quality ora to ora multimodal fundoscopic image in a single scan that will allow for sensitive AI-assisted screening of myopic disease.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1887904},
	author = {Ludwig, Cassie A and Moon, Jade and Garg, Itika and Miller, John B}
}
@article {1608575,
	title = {Statins and the progression of age-related macular degeneration in the United States},
	journal = {PLoS One},
	volume = {16},
	number = {8},
	year = {2021},
	month = {2021},
	pages = {e0252878},
	abstract = {PURPOSE: To study the effect of statin exposure on the progression from non-exudative to exudative age-related macular degeneration (AMD). METHODS: Retrospective cohort study of commercially insured patients diagnosed with non-exudative AMD (n = 231,888) from 2007 to 2015. Time-to-event analysis of the association between exposure to lipid-lowering medications and time from non-exudative AMD to exudative AMD diagnosis was conducted. Outcome measures included progression to exudative AMD, indicated by diagnosis codes for exudative AMD or procedural codes for intravitreal injections. RESULTS: In the year before and after first AMD diagnosis, 11,330 patients were continuously prescribed lipid-lowering medications and 31,627 patients did not take any lipid-lowering medication. Of those taking statins, 21 (1.6\%) patients were on very-high-dose lipophilic statins, 644 (47.6\%) on high-dose lipophilic statins, and 689 (50.9\%) on low-dose lipophilic statins. We found no statistically significant relationship between exposure to low (HR 0.89, 95\% CI 0.83 to 1.38) or high-dose lipophilic statins (HR 1.12, 95\% CI 0.86 to 1.45) and progression to exudative AMD. No patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD, though this difference was not statistically significant due to the subgroup size (p = .23, log-rank test). CONCLUSIONS: No statistically significant relationship was found between statin exposure and risk of AMD progression. Interestingly, no patients taking very-high-dose lipophilic statins progressed to exudative AMD, a finding that warrants further exploration.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0252878},
	author = {Ludwig, Cassie A and Vail, Daniel and Rajeshuni, Nitya A and Al-Moujahed, Ahmad and Rosenblatt, Tatiana and Callaway, Natalia F and Pasricha, Malini Veerappan and Ji, Marco H and Moshfeghi, Darius M}
}
@article {1709661,
	title = {Epidemiology of rhegmatogenous retinal detachment in commercially insured myopes in the United States},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Jun 09},
	pages = {9430},
	abstract = {Myopia is a known risk factor for rhegmatogenous retinal detachment (RRD). Given global trends of increasing myopia, we aimed to determine the absolute risk (incidence rate) of RRD in non-myopes, myopes and high myopes in the United States over ten years. We performed a retrospective cohort study of 85,476,781 commercially insured patients enrolled in the Merative{\texttrademark} Marketscan{\textregistered} Research Database. The incidence rate of RRD in phakic patients in\&nbsp;the United States was 39-fold higher in high myopes than non-myopes (868.83 per 100,000 person-years versus 22.44 per 100,000 person-years)\&nbsp;and three-fold higher in myopes than non-myopes (67.51 per 100,000 person-years\&nbsp;versus\&nbsp;22.44 per 100,000 person-years). The incidence rate was significantly higher in males in each category (P \&lt; 0.01). Combined, the incidence rate of RRD in phakic patients in\&nbsp;the United States from 2007 to 2016\&nbsp;was 25.27 RRDs per 100,000 person-years, a rate higher\&nbsp;than those in prior published studies in North America, South America, Europe, Asia, and Australia.\&nbsp;The absolute risk of myopia and high myopia increased from 2007 to 2016. The\&nbsp;risk of RRD in phakic\&nbsp;high myopes rose\&nbsp;with increasing age. Notably, the magnitude of increased risk of RRD in myopes varied substantially according to the minimum follow-up period in our models and should be accounted for when interpreting data analyses.},
	keywords = {Asia, Humans, Incidence, Male, Myopia, Retinal Detachment, Retrospective Studies, United States},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-35520-x},
	author = {Ludwig, Cassie A and Vail, Daniel and Al-Moujahed, Ahmad and Callaway, Natalia F and Saroj, Namrata and Moshfeghi, Andrew and Moshfeghi, Darius M}
}
@article {1351164,
	title = {Low birth weight is a risk factor for severe retinopathy of prematurity depending on gestational age},
	journal = {PLoS One},
	volume = {9},
	number = {10},
	year = {2014},
	month = {2014},
	pages = {e109460},
	abstract = {OBJECTIVE: To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA). STUDY DESIGN: In total, 2941 infants born \&lt;32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than -2.0 SDS using the Swedish reference and as BW below the 10th percentile using the Canadian reference charts. RESULTS: Univariate analysis showed that low GA (p\&lt;0.001), low BW (p\&lt;0.001), male gender (p\&lt;0.05), low BWSDSCanada (p\&lt;0.001), and SGACanada (p\&lt;0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p\&lt;0.0001), male gender (p\&lt;0.01 and p\&lt;0.05), and an interaction term of BWSDS*GA group (p\&lt;0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA \&lt;26 weeks compared with infants born at GA >=26 weeks calculated with both reference charts (BWSDSSweden, OR = 0.80 vs 0.56; and BWSDSCanada, OR = 0.72 vs 0.41). CONCLUSIONS: Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant{\textquoteright}s degree of immaturity. In more mature infants (GA >=26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches.},
	keywords = {Canada, Female, Gestational Age, Humans, Infant, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Male, Retinopathy of Prematurity, Risk Factors, Sweden, Term Birth},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0109460},
	author = {Lundgren, Pia and Kistner, Anna and Andersson, Eva M and Hansen Pupp, Ingrid and Holmstr{\"o}m, Gerd and Ley, David and Niklasson, Aimon and Smith, Lois E H and Wu, Carolyn and Hellstr{\"o}m, Ann and L{\"o}fqvist, Chatarina}
}
@article {1282136,
	title = {Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity},
	journal = {Acta Paediatr},
	volume = {107},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {759-766},
	abstract = {AIM: This study evaluated the correlation between retinopathy of prematurity (ROP), anaemia and blood transfusions in extremely preterm infants.

METHODS: We included 227 infants born below 28~weeks of gestation at King Edward Memorial Hospital, Perth, Australia, from 2014-2016. Birth characteristics and risk factors for ROP were retrieved, and anaemia and severe anaemia were defined as a haemoglobins of ,
	issn = {1651-2227},
	doi = {10.1111/apa.14187},
	author = {Lundgren, Pia and Athikarisamy, Sam E and Patole, Sanjay and Lam, Geoffrey C and Smith, Lois E and Simmer, Karen}
}
@article {1638571,
	title = {National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity},
	journal = {Acta Paediatr},
	year = {2022},
	month = {2022 Apr 08},
	abstract = {AIM: To describe survival and neonatal morbidities in infants born before 24\&nbsp;weeks of gestation during a 12-year period. METHODS: Data were retrieved from national registries and validated in medical files of infants born before 24\&nbsp;weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. RESULTS: In 2007-2018, 282\&nbsp;live births were recorded at 22\&nbsp;weeks and 460 at 23\&nbsp;weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23\&nbsp;weeks increased from 20\% to 38\% (p\&nbsp;=\&nbsp;0.006) and from 45\% to 67\% (p\&nbsp;\&lt;\&nbsp;0.001) respectively. Caesarean section increased from 12\% to 22\% (p\&nbsp;=\&nbsp;0.038) for infants born at 22\&nbsp;weeks. Neonatal morbidity rates in infants alive at 40\&nbsp;weeks of postmenstrual age (n\&nbsp;=\&nbsp;399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33\% (p\&nbsp;=\&nbsp;0.017) in infants born at 22\&nbsp;weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90\% versus 82\% (p\&nbsp;=\&nbsp;0.044). The number of infants surviving to 40\&nbsp;weeks doubled over time. CONCLUSION: Increased survival of infants born before 24\&nbsp;weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.},
	issn = {1651-2227},
	doi = {10.1111/apa.16354},
	author = {Lundgren, Pia and Morsing, Eva and H{\r a}rd, Anna-Lena and Rakow, Alexander and Hellstr{\"o}m-Westas, Lena and Jacobson, Lena and Johnson, Mats and Holmstr{\"o}m, Gerd and Nilsson, Staffan and Smith, Lois E and S{\"a}vman, Karin and Hellstr{\"o}m, Ann}
}
@article {1430532,
	title = {Leucocytosis is associated with retinopathy of prematurity in extremely preterm infants},
	journal = {Acta Paediatr},
	volume = {108},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {1357-1358},
	issn = {1651-2227},
	doi = {10.1111/apa.14798},
	author = {Lundgren, Pia and Klevebro, Susanna and Brodin, Petter and Smith, Lois E H and Hallberg, Boubou and Hellstr{\"o}m, Ann}
}
@article {1179166,
	title = {Implementing higher oxygen saturation targets reduced the impact of poor weight gain as a predictor for retinopathy of prematurity},
	journal = {Acta Paediatr},
	volume = {107},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {767-773},
	abstract = {AIM: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO ) targets at the Queen Silvia Children{\textquoteright}s Hospital, Gothenburg, Sweden.

METHODS: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO targets were 88-92\% and 142 in 2015-2016 when they were 91-95\%. The subjects were reviewed for birth characteristics, weekly weight and ROP treatment. Data were analysed using the weight, insulin-like growth factor 1, neonatal, ROP (WINROP) prediction tool.

RESULTS: The 2011-2012 infants who needed ROP treatment (12.6\%) had significantly poorer postnatal weight gain than those who did not, but this was not seen in the treated (17.6\%) and nontreated ROP groups in 2015-2016. WINROP sensitivity decreased from 87.5\% in 2011-12 to 48\% in 2015-2016.

CONCLUSION: After the SpO target range was increased from 88-92\% to 91-95\%, postnatal weight gain was no longer a significant risk factor and WINROP lost its ability~to~predict ROP requiring treatment. Risk factors clearly change as neonatal care develops.},
	issn = {1651-2227},
	doi = {10.1111/apa.14049},
	author = {Lundgren, Pia and H{\r a}rd, Anna-Lena and Wilde, {\r A}sa and L{\"o}fqvist, Chatarina and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {341776,
	title = {Weight at first detection of retinopathy of prematurity predicts disease severity},
	journal = {Br J Ophthalmol},
	volume = {98},
	number = {11},
	year = {2014},
	month = {2014 Nov},
	pages = {1565-9},
	abstract = {OBJECTIVE: To investigate whether postnatal weight at first detection of retinopathy of prematurity (ROP) can predict preterm infants who will develop severe ROP warranting treatment. DESIGN: This modern, population-based cohort included 147 infants born at gestational age (GA) \&lt;32 weeks in the Gothenburg region during 2011-2012 and screened for ROP at Sahlgrenska University hospital. GA, birth weight (BW), and weekly postnatal weight from birth until postmenstrual age (PMA) 40 weeks data were retrospectively retrieved. Birth weight SD scores (BWSDS) were calculated. ROP data, including first detected ROP stage, maximal ROP stage, ROP treatment, and PMA at first detected sign of ROP were also retrieved. Weight SDS (WSDS) at first ROP detection was calculated. RESULTS: Stepwise multivariate logistic regression analysis revealed that the best fit-model of risk factors for developing severe ROP warranting treatment included; GA (OR=0.28, CI 95\% 0.12 to 0.66, p\&lt;0.01) and WSDS at first ROP detection (OR=0.22, CI 95\% 0.05 to 0.89, p\&lt;0.05). CONCLUSIONS: Low weight and low WSDS at first ROP detection can be useful predictors for ROP warranting treatment.},
	keywords = {Birth Weight, Female, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Male, Retinopathy of Prematurity, Retrospective Studies, Risk Factors, ROC Curve, Severity of Illness Index, Weight Gain},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-304905},
	author = {Lundgren, Pia and Wilde, {\r A}sa and L{\"o}fqvist, Chatarina and Smith, Lois E H and H{\r a}rd, Anna-Lena and Hellstr{\"o}m, Ann}
}
@article {1460381,
	title = {Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity},
	journal = {Pediatr Res},
	volume = {86},
	number = {2},
	year = {2019},
	month = {2019 Aug},
	pages = {276-282},
	abstract = {BACKGROUND: Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP. METHOD: This prospective study included 78 Swedish infants, born \&lt;28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin <=110 g/L. RESULTS: During postnatal week 1, infants with severe ROP requiring treatment (28\%) more frequently developed anaemia (42.9\% versus 8.0\%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant. CONCLUSIONS: Among infants born \&lt;28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels.},
	issn = {1530-0447},
	doi = {10.1038/s41390-018-0186-6},
	author = {Lundgren, Pia and Hellgren, Gunnel and Pivodic, Aldina and S{\"a}vman, Karin and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1761971,
	title = {Visual outcome at 2.5 years of age in ω-3 and ω-6 long-chain polyunsaturated fatty acid supplemented preterm infants: a follow-up of a randomized controlled trial},
	journal = {Lancet Reg Health Eur},
	volume = {32},
	year = {2023},
	month = {2023 Sep},
	pages = {100696},
	abstract = {BACKGROUND: We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral supplementation with ω-3 and ω-6 long-chain polyunsaturated fatty acids. METHODS: In the Mega Donna Mega clinical trial, EPT infants born at less than 28 weeks of gestation were randomized to receive an enteral supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) from birth to 40 weeks postmenstrual age. In this exploratory follow-up at 2.5 years of corrected age, we assessed visual acuity (VA), refraction, manifest strabismus, and nystagmus. Satisfactory VA was defined as >=20/63. Multiple imputation (MI) was used to address the issue of missing data. FINDINGS: Of 178 children in the trial, 115 (with median gestational age (GA) of 25\&nbsp;+\&nbsp;4/7 weeks and median birth weights of 790\&nbsp;g) were ophthalmologically assessed at a median corrected age of 2.7 years (range 2.0-3.9 years). VA assessment was missing in 42.1\% (75/178), in 41.7\% (35/84) of the AA/DHA supplemented infants, and in 42.6\% (40/94) of the control infants. After MI and adjustments for GA, study center, plurality, and corrected age at VA exam, no significant effect of AA/DHA supplementation was detected in VA outcome (>=20/63) (odds ratio 2.16, confidence interval 95\% 0.99-4.69, p\&nbsp;=\&nbsp;0.053). INTERPRETATION: In this randomized controlled trial follow-up, postnatal supplementation with enteral AA/DHA to EPT children did not significantly alter VA at 2.5 years of corrected age. Due to the high loss to follow-up rate and the limited statistical power, additional studies are needed. FUNDING: The Swedish Medical Research Council $\#$2020-01092, The Gothenburg Medical Society, Government grants under the ALF agreement ALFGBG-717971 and ALFGBG-971188, De Blindas V{\"a}nner, Knut and Alice Wallenberg Foundation - Wallenberg Clinical Scholars, NIHEY017017, EY030904BCHIDDRC (1U54HD090255 Massachusetts Lions Eye Foundation) supported the study.},
	issn = {2666-7762},
	doi = {10.1016/j.lanepe.2023.100696},
	author = {Lundgren, Pia and Jacobson, Lena and Gr{\"a}nse, Lotta and H{\r a}rd, Anna-Lena and S{\"a}vman, Karin and Hansen-Pupp, Ingrid and Ley, David and Nilsson, Anders K and Pivodic, Aldina and Smith, Lois E and Hellstr{\"o}m, Ann}
}
@article {1517206,
	title = {Association between low fatty acid levels and platelet count in infants with Retinopathy of Prematurity},
	journal = {Acta Paediatr},
	volume = {109},
	number = {12},
	year = {2020},
	month = {2020 12},
	pages = {2547-2548},
	issn = {1651-2227},
	doi = {10.1111/apa.15406},
	author = {Lundgren, Pia and Nilsson, Anders K and Hellgren, Gunnel and Pivodic, Aldina and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1593828,
	title = {Efficacy and Safety of 1\% Progesterone Gel to the Forehead for Ocular Chronic Graft-versus-Host Disease},
	journal = {Transplant Cell Ther},
	volume = {27},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {433.e1-433.e8},
	abstract = {There is no Food and Drug Administration-approved treatments for ocular chronic graft-versus-host disease (oGVHD) to date, and current therapeutic options are limited. Forehead application of 1\% progesterone gel provides corneal antinociception in preclinical models, suggesting it may be useful in alleviating ocular irritations. This study was conducted to evaluate the efficacy and safety of 1\% progesterone gel in treating moderate to severe symptomatic oGVHD. Thirty-three patients with oGVHD following allogeneic stem cell transplantation were enrolled in this single-center, sponsor-initiated, prospective exploratory randomized double-masked placebo-controlled phase II clinical trial. The inclusion criteria included a National Institutes of Health consensus score of >=2, moderate to severe ocular discomfort level, and receipt of a stable immunosuppression regimen. Twenty-one of the 22 patients in the progesterone arm and all 11 patients in the placebo arm completed the course of twice-daily forehead drug application for 10 weeks. The changes from baseline of self-reported ocular symptom scores and physician-recorded cornea fluorescein staining scores were analyzed using mixed-model repeated-measures regression model in an intention-to-treat population. The 33 patients included 12 women and 21 men, with a median age of 66 years (range, 24 to 75 years). At 10 weeks, there was a significant reduction in ocular symptoms from baseline in the progesterone group compared with the placebo group in symptom frequency (-30.7 versus -2.2; P \&lt; .001) and severity (-19.8 versus +1.6; P\&nbsp;=\&nbsp;.005). At 10 weeks, there was also greater reduction of cornea fluorescein staining centrally (-1.2 versus +.1; P\&nbsp;=\&nbsp;.001) and inferiorly (-1.4 versus -0.2; P\&nbsp;=\&nbsp;.005). No difference was noted in superior cornea staining. There were no severe adverse events in the progesterone group. Forehead\&nbsp;application\&nbsp;of 1\% progesterone gel\&nbsp;significantly\&nbsp;improved ocular signs and symptoms within 10 weeks. It appears to be a safe and effective new therapy for oGVHD, and a novel mechanism for neuroaxis drug delivery. A multicenter phase III clinical trial is planned for further validation.},
	issn = {2666-6367},
	doi = {10.1016/j.jtct.2021.02.008},
	author = {Luo, Zhonghui K and Domenech-Estarellas, Edgar A and Han, Amy and Lee, Do and Khatri, Ram and Wahl, Jonathan L and Cutler, Corey and Armand, Philippe and Antin, Joseph H and Koreth, John and Gooptu, Mahasweta and Alyea, Edwin P and Soiffer, Robert J and Ho, Vincent T}
}
@article {1364511,
	title = {Visual search performance of patients with vision impairment: effect of JPEG image enhancement},
	journal = {Ophthalmic Physiol Opt},
	volume = {32},
	number = {5},
	year = {2012},
	month = {2012 Sep},
	pages = {421-8},
	abstract = {PURPOSE: To measure natural image search performance in patients with central vision impairment. To evaluate the performance effect for a JPEG based image enhancement technique using the visual search task. METHODS: One hundred and fifty JPEG images were presented on a touch screen monitor in either an enhanced or original version to 19 patients (visual acuity 0.4-1.2 logMAR, 6/15 to 6/90, 20/50 to 20/300) and seven normally sighted controls (visual acuity -0.12 to 0.1 logMAR, 6/4.5 to 6/7.5, 20/15 to 20/25). Each image fell into one of three categories: faces, indoors, and collections. The enhancement was realized by moderately boosting a mid-range spatial frequency band in the discrete cosine transform (DCT) coefficients of the image luminance component. Participants pointed to an object in a picture that matched a given target displayed at the upper-left corner of the monitor. Search performance was quantified by the percentage of correct responses, the median search time of correct responses, and an {\textquoteright}integrated performance{\textquoteright} measure - the area under the curve of cumulative correct response rate over search time. RESULTS: Patients were able to perform the search tasks but their performance was substantially worse than the controls. Search performances for the three image categories were significantly different (p \&lt;= 0.001) for all the participants, with searching for faces being the most difficult. When search time and correct response were analyzed separately, the effect of enhancement led to increase in one measure but decrease in another for many patients. Using the integrated performance, it was found that search performance declined with decrease in acuity (p = 0.005). An improvement with enhancement was found mainly for the patients whose acuity ranged from 0.4 to 0.8 logMAR (6/15 to 6/38, 20/50 to 20/125). Enhancement conferred a small but significant improvement in integrated performance for indoor and collection images (p = 0.025) in the patients. CONCLUSION: Search performance for natural images can be measured in patients with impaired vision to evaluate the effect of image enhancement. Patients with moderate vision loss might benefit from the moderate level of enhancement used here.},
	keywords = {Adult, Aged, Aged, 80 and over, Analysis of Variance, Computer Terminals, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Male, Middle Aged, Photic Stimulation, Task Performance and Analysis, Vision Disorders, Visual Perception},
	issn = {1475-1313},
	doi = {10.1111/j.1475-1313.2012.00908.x},
	author = {Luo, Gang and Satgunam, PremNandhini and Peli, Eli}
}
@article {313221,
	title = {Salient stimulus attracts focus of peri-saccadic mislocalization},
	journal = {Vision Res},
	volume = {100},
	year = {2014},
	month = {2014 Jul},
	pages = {93-8},
	abstract = {Visual localization during saccadic eye movements is prone to error. Flashes shortly before and after the onset of saccades are usually perceived to shift towards the saccade target, creating a "compression" pattern. Typically, the saccade landing point coincides with a salient saccade target. We investigated whether the mislocalization focus follows the actual saccade landing point or a salient stimulus. Subjects made saccades to either a target or a memorized location without target. In some conditions, another salient marker was presented between the initial fixation and the saccade landing point. The experiments were conducted on both black and picture backgrounds. The results show that: (a) when a saccade target or a marker (spatially separated from the saccade landing point) was present, the compression pattern of mislocalization was significantly stronger than in conditions without them, for both black and picture background conditions, and (b) the mislocalization focus tended towards the salient stimulus regardless of whether it was the saccade target or the marker. Our results suggest that a salient stimulus presented in the scene may have an attracting effect and therefore contribute to the non-uniformity of saccadic mislocalization of a probing flash.},
	keywords = {Adult, Analysis of Variance, Humans, Judgment, Male, Photic Stimulation, Saccades, Space Perception},
	issn = {1878-5646},
	doi = {10.1016/j.visres.2014.04.008},
	author = {Luo, Gang and Garaas, Tyler and Pomplun, Marc}
}
@article {1435407,
	title = {Descemet Membrane Endothelial Keratoplasty Failure Associated with Innate Immune Activation},
	journal = {Ophthalmology},
	volume = {126},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {1462-1464},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.04.016},
	author = {Lu{\v z}nik, Zala and Oellerich, Silke and Roesch, Karin and Yin, Jia and Zumbansen, Markus and Franken, Lars and Melles, Gerrit R J and Dana, Reza}
}
@article {1549010,
	title = {Regulatory T Cells in Angiogenesis},
	journal = {J Immunol},
	volume = {205},
	number = {10},
	year = {2020},
	month = {2020 Nov 15},
	pages = {2557-2565},
	abstract = {Regulatory T cells (Tregs) are crucial mediators of immune homeostasis. They regulate immune response by suppressing inflammation and promoting self-tolerance. In addition to their immunoregulatory role, a growing body of evidence highlights the dynamic role of Tregs in angiogenesis, the process of forming new blood vessels. Although angiogenesis is critically important for normal tissue regeneration, it is also a hallmark of pathological processes, including malignancy and chronic inflammation. Interestingly, the role of Tregs in angiogenesis has been shown to be highly tissue- and context-specific and as a result can yield either pro- or antiangiogenic effects. For these reasons, there is considerable interest in determining the molecular underpinnings of Treg-mediated modulation of angiogenesis in different disease states. The present review summarizes the role of Tregs in angiogenesis and mechanisms by which Tregs regulate angiogenesis and discusses how these mechanisms differ in homeostatic and pathological settings.},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.2000574},
	author = {Lu{\v z}nik, Zala and Anchouche, Sonia and Dana, Reza and Yin, Jia}
}
@article {1532348,
	title = {Association of α-Melanocyte-Stimulating Hormone With Corneal Endothelial Cell Survival During Oxidative Stress and Inflammation-Induced Cell Loss in Donor Tissue},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Sep 17},
	abstract = {Importance: Corneal endothelial cell (CEnC) damage and loss are major issues in eye banking and transplantation. The underlying mechanisms for CEnC loss are incompletely understood, and cytoprotective strategies that enhance CEnC viability could have a major effect on donor tissue quality and graft survival. Objective: To investigate the cytoprotective role of neuropeptide α-melanocyte-stimulating hormone (α-MSH) in preventing CEnC loss in eye bank cold-stored corneas under oxidative and inflammatory cytokine-induced stress. Design, Setting, and Participants: This single-center comparative research study conducted ex vivo experiments using 16 pairs of research-grade human donor corneas (courtesy of Eversight Eye Bank). Data were collected from June 2018 to November 2019, and data were analyzed from December 2019 to January 2020. Exposures: Two corneas from the same donor were randomized to either control or 0.1 mmol/L of α-MSH treatment and then subjected to oxidative stress (1.4 mmol/L of hydrogen peroxide-phosphate-buffered saline for 15 minutes at 37 {\textdegree}C; n = 8 pairs) or cytokine-induced stress (100 ng/mL of tumor necrosis factor-α and 100 ng/mL of interferon γ for 18 hours at 37 {\textdegree}C; n = 8 pairs). Corneas were then stored at 4 {\textdegree}C. Specular images were taken at baseline and repeated twice per week using a calibrated wide-field specular microscope. CEnC viability was assessed using a fluorescent live/dead viability assay. Main Outcome and Measures: Endothelial morphometry analysis, central corneal thickness measurements, and percentage of dead cells at day 11. Results: Of 16 donors who provided corneas, 9 (56\%) were male, and the mean (SD) age was 57.9 (12.4) years. Corneas were paired, and baseline parameters were comparable between all groups. At all time points, CEnC loss was lower in the α-MSH groups compared with the control groups. This difference was statistically significant after cytokine-induced stress (20.2\% vs 35.2\%; sample estimate of median, -14.9; 95\% CI, -23.6 to -6.3; P = .008). Compared with the control group, α-MSH treatment resulted in a smaller increase in central corneal thickness (cytokine-induced stress: 89.3 μm vs 169.8 μm; sample estimate of median, -84.9; 95\% CI, -131.5 to -41.6; P = .008; oxidative stress: 43.6 μm vs 111.9 μm; sample estimate of median, -68.8; 95\% CI, -100.0 to -34.5; P = .008) and a smaller proportion of cell death (cytokine-induced stress: 2.7\% vs 10.4\%; difference, -7.7; 95\% CI, -13.1 to -2.4; P = .01; oxidative stress: 2.9\% vs 12.4\%; difference, 9.5; 95\% CI, 5.1 to 13.9; P = .006). Conclusions and Relevance: In this study, α-MSH treatment attenuated CEnC loss during cold storage after acute oxidative and cytokine-induced stress in human eye bank cold-stored corneas. These data suggest that supplementation of corneal storage solution with α-MSH may positively affect CEnC survival after transplant and protect the endothelium from proinflammatory cytokines and oxidative stress after full-thickness or endothelial keratoplasty, which is particularly valuable in patients at high risk of graft failure.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.3413},
	author = {Lu{\v z}nik, Zala and Sun, Zhongmou and Nakagawa, Hayate and Taylor, Andrew W and Jurkunas, Ula V and Yin, Jia and Dana, Reza}
}
@article {1623370,
	title = {The Neuropeptide Alpha-Melanocyte-Stimulating Hormone Is Critical for Corneal Endothelial Cell Protection and Graft Survival after Transplantation},
	journal = {Am J Pathol},
	volume = {192},
	number = {2},
	year = {2022},
	month = {2022 02},
	pages = {270-280},
	abstract = {Corneal transplantation is the most common form of tissue transplantation. The success of corneal transplantation mainly relies on the integrity of corneal endothelial cells (CEnCs), which maintain tissue transparency by pumping out excess water from the cornea. After transplantation, the rate of CEnC loss far exceeds that seen with normal aging, which can threaten sight. The underlying mechanisms are poorly understood. Alpha-melanocyte-stimulating hormone (α-MSH) is a neuropeptide that is constitutively found in the aqueous humor with both cytoprotective and immunomodulatory effects. The curent study found high expression of melanocortin 1 receptor (MC1R), the receptor for α-MSH, on CEnCs. The effect of α-MSH/MC1R signaling on endothelial function and allograft survival in\&nbsp;vitro and in\&nbsp;vivo was investigated using MC1R signaling-deficient mice (Mc1re/e mice with a nonfunctional MC1R). Herein, the results indicate that in addition to its well-known immunomodulatory effect, α-MSH has cytoprotective effects on CEnCs after corneal transplantation, and the loss of MC1R signaling significantly decreases long-term graft survival in\&nbsp;vivo. In conclusion, α-MSH/MC1R signaling is critical for CEnC function and graft survival after corneal transplantation.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.10.016},
	author = {Lu{\v z}nik Marzidov{\v s}ek, Zala and Blanco, Tomas and Sun, Zhongmou and Alemi, Hamid and Ortiz, Gustavo and Nakagawa, Hayate and Chauhan, Sunil K and Taylor, Andrew W and Jurkunas, Ula V and Yin, Jia and Dana, Reza}
}
@article {1363147,
	title = {Morphology of astrocytes in a glaucomatous optic nerve},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {2},
	year = {2013},
	month = {2013 Feb 01},
	pages = {909-17},
	abstract = {PURPOSE: To establish the morphologic changes of astrocytes in the glial lamina of glaucomatous mice. METHODS: A strain of mice that expresses GFP in individual astrocytes (hGFAPpr-GFP) was crossed into the DBA/2J strain that develops glaucoma. In the resulting strain (D2.hGFAPpr-GFP) we assessed the severity of glaucoma by staining the retina for neurofilaments and counting the neurons of the retinal ganglion cell layer. We observed the morphology of astrocytes in the glial lamina of the optic nerves. RESULTS: D2.hGFAPpr-GFP mice developed glaucoma in an age-dependent manner. Astrocytes in the glial lamina showed morphologic changes that correlated with the severity of glaucoma. The cells showed thickening of processes from 1.3 {\textpm} 0.28 μm in nondiseased animals to 1.71 {\textpm} 0.46 μm in eyes with moderate glaucoma and 2.1 {\textpm} 0.42 μm in those with severe glaucoma. Their spatial coverage, as determined by their convex polygon area, was reduced in eyes with severe glaucoma. The astrocytes in severely glaucomatous optic nerves also showed simplification of their processes. In 6-month-old mice with no obvious signs of degeneration in the retina, we found astrocytes with appendages growing out of primary astrocyte processes into the axon bundles. This localized hypertrophy of processes was never observed in the hGFAPpr-GFP strain. CONCLUSIONS: Confirming results after optic nerve crush, astrocytes in glaucomatous optic nerves had thickened and simplified processes, and reduced spatial coverage. We also found evidence of localized sprouting of new processes in early stages of the disease, before detectable changes in ganglion cell number.},
	keywords = {Animals, Astrocytes, Disease Models, Animal, Female, Glaucoma, Immunohistochemistry, Male, Mice, Mice, Inbred DBA, Optic Nerve, Severity of Illness Index},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-10109},
	author = {Lye-Barthel, Ming and Sun, Daniel and Jakobs, Tatjana C}
}
@article {1732661,
	title = {Anti-Inflammatory and Pro-Resolving Actions of the N-Terminal Peptides Ac2-26, Ac2-12, and Ac9-25 of Annexin A1 on Conjunctival Goblet Cell Function},
	journal = {Am J Pathol},
	volume = {193},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1817-1832},
	abstract = {Annexin A1 (AnxA1) is the primary mediator of the anti-inflammatory actions of glucocorticoids. AnxA1 functions as a pro-resolving mediator in cultured rat conjunctival goblet cells to ensure tissue homeostasis through stimulation of intracellular [Ca2+] ([Ca2+]i) and mucin secretion. AnxA1 has several N-terminal peptides with anti-inflammatory properties of their own, including Ac2-26, Ac2-12, and Ac9-25. The increase in [Ca2+]i caused by AnxA1 and its N-terminal peptides in goblet cells was measured to determine the formyl peptide receptors used by the compounds and the action of the peptides on histamine\&nbsp;stimulation. Changes in [Ca2+]i were determined by using a fluorescent Ca2+ indicator. AnxA1 and its peptides each activated formyl peptide receptors in goblet cells. AnxA1 and Ac2-26 at 10-12 mol/L and Ac2-12 at 10-9 mol/L inhibited the histamine-stimulated increase in [Ca2+]i, as did resolvin D1 and lipoxin A4 at 10-12 mol/L, whereas Ac9-25 did not. AnxA1 and Ac2-26 counter-regulated the H1 receptor through the p42/p44 mitogen-activated protein\&nbsp;kinase/extracellular regulated kinase 1/2, β-adrenergic receptor kinase, and protein kinase C pathways, whereas Ac2-12 counter-regulated only through β-adrenergic receptor kinase. In conclusion, current data show that the N-terminal peptides Ac2-26 and Ac2-12, but not Ac9-25, share multiple functions with the full-length AnxA1 in goblet cells, including inhibition of histamine-stimulated increase in [Ca2+]i and counter-regulation of the H1\&nbsp;receptor. These actions suggest a potential pharmaceutical application of the AnxA1 N-terminal peptides Ac2-26 and Ac2-12 in homeostasis and ocular inflammatory diseases.},
	keywords = {Animals, Annexin A1, Anti-Inflammatory Agents, beta-Adrenergic Receptor Kinases, Goblet Cells, Histamine, Peptides, Rats, Receptors, Formyl Peptide},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2023.05.020},
	author = {Lyngstadaas, Anne V and Olsen, Markus V and Bair, Jeffrey and Yang, Menglu and Hodges, Robin R and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1528700,
	title = {Vascular Density of Deep, Intermediate and Superficial Vascular Plexuses Are Differentially Affected by Diabetic Retinopathy Severity.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {10},
	year = {2020},
	pages = {53},
	author = {Ashraf M and Sampani K and Clermont A and Abu-Qamar O and Rhee J and Silva PS and Aiello LP and Sun JK}
}
@article {1466922,
	title = {Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema},
	journal = {J Neuroophthalmol},
	volume = {39},
	number = {3},
	year = {2019},
	month = {2019 Sep},
	pages = {299-307},
	abstract = {OBJECTIVE: Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP. METHODS: Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension. RESULTS: Reduced pituitary gland height was moderately sensitive for IIH WP (80\%) but had low specificity (64\%). Increased optic nerve sheath diameter was less sensitive (51\%) and only moderately specific (83\%). Flattening of the posterior globe was highly specific (97\%) but had low sensitivity (57\%). Transverse venous sinus stenosis was moderately sensitive for IIH WP (78\%) but of undetermined specificity. A combination of any 3 of 4 MRI features was nearly 100\% specific, while maintaining a sensitivity of 64\%. Of patients with CH + EOP, 30\% had 3 or more MRI features, suggesting IIH WOP in those patients. CONCLUSION: A combination of any 3 of 4 MRI features is highly specific for intracranial hypertension and suggests IIH WOP when present in patients with chronic headache and no papilledema.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000767},
	author = {M Mallery, Robert and Rehmani, Obeidurahman F and Woo, John H and Chen, Yin Jie and Reddi, Sudama and Salzman, Karen L and Pinho, Marco C and Ledbetter, Luke and Tamhankar, Madhura A and Shindler, Kenneth S and Digre, Kathleen B and Friedman, Deborah I and Liu, Grant T}
}
@article {1295873,
	title = {Visual Fixation Instability in Multiple Sclerosis Measured Using SLO-OCT},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {1},
	year = {2018},
	month = {2018 Jan 01},
	pages = {196-201},
	abstract = {Purpose: Precise measurements of visual fixation and its instability were recorded during optical coherence tomography (OCT) as a marker of neural network dysfunction in multiple sclerosis (MS), which could be used to monitor disease progression or response to treatment. Methods: A total of 16 MS patients and 26 normal subjects underwent 30 seconds of scanning laser ophthalmoscope (SLO)-based eye tracking during OCT scanning of retinal layer thickness. Study groups consisted of normal eyes, MS eyes without prior optic neuritis (MS wo ON), and MS eyes with prior optic neuritis (MS + ON). Kernel density estimation quantified fixation instability from the distribution of fixation points on the retina. In MS wo ON eyes, fixation instability was compared to other measures of visual and neurologic function. Results: Fixation instability was increased in MS wo ON eyes (0.062 deg2) compared to normal eyes (0.030 deg2, P = 0.015). A further increase was seen for MS + ON eyes (0.11 deg2) compared to MS wo ON (P = 0.04) and normal (P = 0.006) eyes. Fixation instability correlated weakly with ganglion cell layer (GCL) volume and showed no correlation with low-contrast letter acuity, EDSS score, or SDMT score. Conclusions: Fixation instability reflects the integrity of a widespread neural network germane to visual processing and ocular motor control, and is disturbed in MS. Further study of visual fixation, including the contribution of microsaccades to fixation instability, may provide insight into the localization of fixation abnormalities in MS and introduce innovative and easily measured outcomes for monitoring progression and treatment response.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-22391},
	author = {M Mallery, Robert and Poolman, Pieter and J Thurtell, Matthew and Full, Jan M and Ledolter, Johannes and Kimbrough, Dorlan and Frohman, Elliot M and Frohman, Teresa C and Kardon, Randy H}
}
@article {836916,
	title = {The Pattern of Visual Fixation Eccentricity and Instability in Optic Neuropathy and Its Spatial Relationship to Retinal Ganglion Cell Layer Thickness.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {9},
	year = {2016},
	month = {2016 Jul 1},
	pages = {OCT429-37},
	abstract = {PURPOSE: The purpose of this study was to assess whether clinically useful measures of fixation instability and eccentricity can be derived from retinal tracking data obtained during optical coherence tomography (OCT) in patients with optic neuropathy (ON) and to develop a method for relating fixation to the retinal ganglion cell complex (GCC) thickness. METHODS: Twenty-nine patients with ON underwent macular volume OCT with 30 seconds of confocal scanning laser ophthalmoscope (cSLO)-based eye tracking during fixation. Kernel density estimation quantified fixation instability and fixation eccentricity from the distribution of fixation points on the retina. Preferred ganglion cell layer loci (PGCL) and their relationship to the GCC thickness map were derived, accounting for radial displacement of retinal ganglion cell soma from their corresponding cones. RESULTS: Fixation instability was increased in ON eyes (0.21 deg2) compared with normal eyes (0.06982 deg2; P \&lt; 0.001), and fixation eccentricity was increased in ON eyes (0.48{\textdegree}) compared with normal eyes (0.24{\textdegree}; P = 0.03). Fixation instability and eccentricity each correlated moderately with logMAR acuity and were highly predictive of central visual field loss. Twenty-six of 35 ON eyes had PGCL skewed toward local maxima of the GCC thickness map. Patients with bilateral dense central scotomas had PGCL in homonymous retinal locations with respect to the fovea. CONCLUSIONS: Fixation instability and eccentricity measures obtained during cSLO-OCT assess the function of perifoveal retinal elements and predict central visual field loss in patients with ON. A model relating fixation to the GCC thickness map offers a method to assess the structure-function relationship between fixation and areas of preserved GCC in patients with ON.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18916},
	author = {M Mallery, Robert and Poolman, Pieter and J Thurtell, Matthew and Wang, Jui-Kai and K Garvin, Mona and Ledolter, Johannes and Kardon, Randy H}
}
@article {1445351,
	title = {Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema: Response},
	journal = {J Neuroophthalmol},
	volume = {39},
	number = {3},
	year = {2019},
	month = {2019 Sep},
	pages = {439},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000808},
	author = {M Mallery, Robert and Friedman, Deborah I and Digre, Kathleen B and Liu, Grant T}
}
@article {1538318,
	title = {Novel Method to Determine Target Refraction in Cataract Surgery for Patients Dependent on Therapeutic Scleral Lenses},
	journal = {Eye Contact Lens},
	volume = {47},
	number = {6},
	year = {2021},
	month = {2021 Jun 01},
	pages = {352-355},
	abstract = {OBJECTIVES: To evaluate a novel approach to determine the refractive target for patients undergoing cataract surgery who are dependent on therapeutic scleral lenses, to avoid the need for postoperative scleral lens replacement. METHODS: Retrospective single-surgeon case series. The target refraction for intraocular lens selection was determined by considering the effective scleral lens system power. This was calculated by adding the known scleral lens spherical power to the difference between the scleral lens base curve and the average keratometry value. RESULTS: Six eyes from three patients with moderate myopia or emmetropia with ocular graft versus host disease dependent on therapeutic scleral lenses underwent cataract surgery with intraocular lens selection based on this method. All six eyes had corrected visual acuities of 20/30 or better while wearing their previous scleral lenses at the postoperative week 1 visit. All six eyes resumed full-time scleral lens use 1 week after phacoemulsification and did not require scleral lens replacement. CONCLUSIONS: Using this method, patients requiring therapeutic scleral lenses can quickly experience optimal vision, comfort, and ocular surface protection 1 week after cataract surgery. These patients can continue to use their existing scleral lenses and avoid the costs and burdens associated with lens replacement.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000747},
	author = {Ma, Kevin K and Luo, Zhonghui K}
}
@article {836921,
	title = {Prevention of Proliferative Vitreoretinopathy by Suppression of Phosphatidylinositol 5-Phosphate 4-Kinases.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {8},
	year = {2016},
	month = {2016 Jul 1},
	pages = {3935-43},
	abstract = {PURPOSE: Previous studies have shown that vitreous stimulates degradation of the tumor suppressor protein p53 and that knockdown of phosphatidylinositol 5-phosphate 4-kinases (PI5P4Kα and -β) abrogates proliferation of p53-deficient cells. The purpose of this study was to determine whether vitreous stimulated expression of PI5P4Kα and -β and whether suppression of PI5P4Kα and -β would inhibit vitreous-induced cellular responses and experimental proliferative vitreoretinopathy (PVR). METHODS: PI5P4Kα and -β encoded by PIP4K2A and 2B, respectively, in human ARPE-19 cells were knocked down by stably expressing short hairpin (sh)RNA directed at human PIP4K2A and -2B. In addition, we rescued expression of PI5P4Kα and -β by re-expressing mouse PIP4K2A and -2B in the PI5P4Kα and -β knocked-down ARPE-19 cells. Expression of PI5P4Kα and -β was determined by Western blot and immunofluorescence. The following cellular responses were monitored: cell proliferation, survival, migration, and contraction. Moreover, the cell potential of inducing PVR was examined in a rabbit model of PVR effected by intravitreal cell injection. RESULTS: We found that vitreous enhanced expression of PI5P4Kα and -β in RPE cells and that knocking down PI5P4Kα and -β abrogated vitreous-stimulated cell proliferation, survival, migration, and contraction. Re-expression of mouse PIP4Kα and -β in the human PI5P4Kα and -β knocked-down cells recovered the loss of vitreous-induced cell contraction. Importantly, suppression of PI5P4Kα and -β abrogated the pathogenesis of PVR induced by intravitreal cell injection in rabbits. Moreover, we revealed that expression of PI5P4Kα and -β was abundant in epiretinal membranes from PVR grade C patients. CONCLUSIONS: The findings from this study indicate that PI5P4Kα and -β could be novel therapeutic targets for the treatment of PVR.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-19405},
	author = {Ma, Gaoen and Duan, Yajian and Huang, Xionggao and Qian, Cynthia X and Chee, Yewlin and Mukai, Shizuo and Cui, Jing and Samad, Arif and Matsubara, Joanne Aiko and Kazlauskas, Andrius and D{\textquoteright}Amore, Patricia A and Gu, Shuyan and Lei, Hetian}
}
@article {1295872,
	title = {Multiple Eyelid Cysts (Apocrine and Eccrine Hidrocystomas, Trichilemmal Cyst, and Hybrid Cyst) in a Patient With a Prolactinoma},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {3},
	year = {2018},
	month = {2018 May/Jun},
	pages = {e83-e85},
	abstract = {A 53-year-old man presented with smooth-domed, variegated cysts (polycystic disease) of all 4 eyelids, worse on the left side. Some of the cysts were clear, while others were creamy-white colored. In addition, multiple, very fine vesicopapules were noted along the eyelid margins. Histopathologic examination revealed a trichilemmal cyst, several pure apocrine hidrocystomas displaying multiple chambers, a hybrid cyst, and many small eccrine cysts of the deep dermis. The apocrine lesions, including the small ones at the eyelid margins, predominated. Smooth muscle actin sometimes positively stained outer myoepithelial cells in some of the apocrine cysts, which helped to distinguish them from eccrine cysts. Most noteworthy was the fact that the patient had been diagnosed with a prolactinoma 20 years earlier. There is only 1 previous report of multiple apocrine cysts and an antecedent prolactinoma in the dermatologic literature. This syndrome should be separated from that of Sch{\"o}pf-Schulz-Passarge, which manifests multiple small eyelid apocrine cysts and other ectodermal dysplasias without any association with neoplasia, and from that of focal dermal hypoplasia (Goltz-Gorlin) syndrome with apocrine cysts but again without neoplasia.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001069},
	author = {Ma, Lina and Jakobiec, Frederick A and Wolkow, Natalie and Dryja, Thaddeus P and Borodic, Gary E}
}
@article {1593857,
	title = {Enhanced migration of engrafted retinal progenitor cells into the host retina via disruption of glial barriers},
	journal = {Mol Vis},
	volume = {27},
	year = {2021},
	month = {2021},
	pages = {300-308},
	abstract = {Purpose: Migration and integration remain critical challenges for stem cell replacement therapy. Glial barriers play an important role in preventing cell migration and integration. The purpose of this study was to investigate the effect and mechanisms of chondroitinase ABC on the migration of murine retinal progenitor cells (mRPCs) transplanted into the subretinal space of B6 mice. Methods: mRPCs were harvested from the neural retinas of P1 enhanced green fluorescent protein (GFP) B6 mice. Two μl containing 2 {\texttimes} 105 expanded RPCs alone or combined with chondroitinase ABC in suspension were injected into the subretinal space of the recipient B6 mice. Immunohistochemistry was performed on the recipient B6 retinas to evaluate the glial barrier formation and migration of the mRPCs. Western blotting was also used to check the expression of the glial barriers. Results: Glial fibrillary acidic protein (GFAP) and vimentin could be seen around the transplanted mRPCs in the B6 mice. Formation of glial barriers prevented the migration of donor cells into the retinal layers. Chondroitinase ABC promoted the migration and survival rates of the engrafted retinal progenitor cells in the retinal layers of recipient B6 mice. Injection induced upregulation of GFAP, chondroitin, and CD44 expression. Chondroitinase ABC disrupted the glial barriers. The CD44 around the mRPCs was much lower in the chondroitinase group. However, the CD44 in the retinal layers was considerably higher in the chondroitinase group. With the employment of chondroitinase ABC, more cells migrated into the outer nuclear layer or inner nuclear layer. The chondroitin and CD44 expression decreased 3 weeks after transplantation in the chondroitinase ABC group. Conclusions: Chondroitinase ABC degraded glial barriers and enhanced the migration of transplanted mouse retinal progenitor cells. Chondroitinase ABC may also have induced activation of the CD44 signaling pathway to exert the effect.},
	issn = {1090-0535},
	author = {Ma, Jian and Chen, Min and Ai, Jing and Young, Michael J and Ge, Jian}
}
@article {1351165,
	title = {Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation},
	journal = {Mol Vis},
	volume = {20},
	year = {2014},
	month = {2014},
	pages = {881-93},
	abstract = {PURPOSE: The clinical phenotype of advanced stage retinopathy of prematurity (ROP, stages 4 and 5) cannot be replicated in an animal model. To dissect the molecular events that can lead up to advanced ROP, we examined subretinal fluid (SRF) and surgically dissected retrolental membranes from patients with advanced ROP to evaluate its influences on cell proliferation, angiogenic properties, and macrophage polarity. METHODS: We compared our findings to SRF collected from patients with uncomplicated rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy and surgically dissected epiretinal membrane from eyes with macular pucker. All subretinal fluid samples were equalized for protein. The angiogenic potential of SRF from ROP eyes was measured using a combination of capillary cord formation in a fibrin clot assay, and its proliferative effect was tested with a DNA synthesis of human retinal microvascular endothelial cells. Findings were compared with SRF collected from participants with uncomplicated rhegmatogenous RD without proliferative vitreoretinopathy. The ability of SRF to induce nitric oxide production was measured in vitro using murine J774A.1 macrophages. Cytokine profiles of SRF from ROP and RD eyes were measured using a multienzyme-linked immunosorbent assay (ELISA). Fluorescent immunohistochemistry of retrolental membranes from ROP was performed to detect the presence of leukocytes and the composition of tissue macrophages using markers for M1 and M2 differentiation. RESULTS: The cytokine composition in SRF revealed that in ROP, not only were several proangiogenic factors were preferentially elevated but also the profile of proinflammatory factors was also increased compared to the RD eyes. SRF from ROP eyes supported cell proliferation and endothelial cord formation while SRF from RD eyes had inhibitory effects. SRF from eyes with ROP but not RD robustly induced nitric oxide production in macrophages. Furthermore, fluorescent immunostaining revealed a preponderance of M1 over M2 macrophages in retrolental fibrous membranes from ROP eyes. The cytokine profile and biologic properties of SRF in ROP promote a proangiogenic environment, which supports the maintenance and proliferation of fibrous membranes associated with advanced stages of ROP. In contrast, SRF from RD eyes exhibits a suppressive environment for endothelial cell proliferation and angiogenesis. CONCLUSIONS: Our investigation demonstrates that the microenvironment in advanced ROP eyes is proangiogenic and proinflammatory. These findings suggest that management of advanced ROP should not be limited to the surgical removal of the fibrovascular membranes and antiangiogenic therapy but also directed to anti-inflammatory therapy and to promote M2 activation over M1 activity.},
	keywords = {Animals, Capillaries, Cell Polarity, Cell Proliferation, Cells, Cultured, Cytokines, Humans, Immunohistochemistry, Infant, Inflammation Mediators, Macrophages, Mice, Neovascularization, Physiologic, Nitric Oxide, Nitrites, Retinal Detachment, Retinopathy of Prematurity, Subretinal Fluid},
	issn = {1090-0535},
	author = {Ma, Jie and Mehta, Manisha and Lam, Godfrey and Cyr, Desire{\'e} and Ng, Tat Fong and Hirose, Tatsuo and Tawansy, Khaled A and Taylor, Andrew W and Lashkari, Kameran}
}
@article {1538351,
	title = {Reversal of Visual Loss From Skull Base Osteomyelitis in a Pediatric Patient},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {4},
	year = {2021},
	month = {2021 Dec 01},
	pages = {e728-e730},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001110},
	author = {Ma, Kevin K and Robson, Caroline D and Gaier, Eric D and Gise, Ryan}
}
@article {416846,
	title = {Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival.},
	journal = {PLoS One},
	volume = {10},
	number = {4},
	year = {2015},
	month = {2015},
	pages = {e0125695},
	abstract = {We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNPIGF-TD cells displayed enhanced survival, and increased neurite extension and branching as compared to hNPTD or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNPIGF-TD cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNPIGF-TD cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0125695},
	author = {Ma, Jie and Guo, Chenying and Guo, Caiwei and Sun, Yu and Liao, Tiffany and Beattie, Ursula and L{\'o}pez, Francisco J and Chen, Dong Feng and Lashkari, Kameran}
}
@article {560266,
	title = {A Novel Technique for Amniotic Membrane Transplantation in Patients with Acute Stevens-Johnson Syndrome.},
	journal = {Ocul Surf},
	volume = {14},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {31-6},
	abstract = {Cryopreserved amniotic membrane (AM) transplantation is an emerging technique that is becoming the gold standard for the management of acute Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN). We describe a novel surgical technique utilizing a single, large sheet of AM (5 x 10 cm) and a custom-made forniceal ring, which facilitates AM placement. Our technique is easy to use and minimizes suturing\&nbsp;and manipulation of ocular tissues, resulting in decreased operative time. This technique may be applied in the management of multiple ocular surface disease processes, including chemical or thermal burns, severe ocular graft versus host disease (GVHD), and other autoimmune diseases.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2015.07.002},
	author = {Ma, Kelly N and Thanos, Aristomenis and Chodosh, James and Shah, Ankoor S and Mantagos, Iason S}
}
@article {1304386,
	title = {Management of Ocular Cicatricial Pemphigoid with Intravenous Immunoglobulin Monotherapy},
	journal = {Ocul Immunol Inflamm},
	year = {2018},
	month = {2018 Mar 08},
	pages = {1-7},
	abstract = {PURPOSE: To assess the long-term efficacy and safety of IVIg monotherapy in patients with recalcitrant ocular cicatricial pemphigoid (OCP). METHODS: A chart review of all OCP patients seen at the Massachusetts Eye Research and Surgery Institution (MERSI) between 2005 and 2015 was completed. Stage was graded by using the Foster grading system. IVIg infusion was 2g/kg/cycle administered in 3 consecutive days monthly. RESULTS: Of 512 OCP patients, 17 patients (34 eyes) treated with IVIg monotherapy were identified. Seven were female and ten were male. The average age at diagnosis was 60.7-year-old. The follow up time ranged from 12 to 140 months. Twenty-six eyes (76.5\%) achieved remission. Nine remission eyes received cataract surgeries, and 2 of them had relapse (22.2\%). The other 17 eyes did not undergo ocular surgery and remained in remission. IVIg monotherapy showed high efficacy in stage 1 OCP (7/7, 100\%). Ocular surgery can be associated with OCP relapse (Table 2). CONCLUSIONS: IVIg monotherapy is an effective and safe therapy in patients with recalcitrant OCP. Ocular surgery can be associated with OCP relapse.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2018.1433302},
	author = {Ma, Lina and You, Caiyun and Hernandez, Mikhail and Maleki, Arash and Lasave, Andres and Schmidt, Alexander and Stephenson, Andrew and Zhao, Thongzen and Anesi, Stephen and Foster, C Stephen}
}
@article {1798521,
	title = {Tumor Pigmentation Does Not Affect Light-Activated Belzupacap Sarotalocan Treatment but Influences Macrophage Polarization in a Murine Melanoma Model},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {65},
	number = {1},
	year = {2024},
	month = {2024 Jan 02},
	pages = {42},
	abstract = {PURPOSE: Pigmentation in uveal melanoma is associated with increased malignancy and is known as a barrier for photodynamic therapy. We investigated the role of pigmentation in tumor behavior and the response to light-activated Belzupacap sarotalocan (Bel-sar) treatment in a pigmented (wild type) and nonpigmented (tyrosinase knock-out [TYR knock-out]) cell line in vitro and in a murine model.

METHODS: The B16F10 (TYR knock-out) was developed using CRISPR/Cas9. After the treatment with light-activated Bel-sar, cytotoxicity and exposure of damage-associated molecular patterns (DAMPs) were measured by flow cytometry. Treated tumor cells were co-cultured with bone marrow-derived macrophages (BMDMs) and dendritic cells (DCs) to assess phagocytosis and activation. Both cell lines were injected subcutaneously in syngeneic C57BL/6 mice.

RESULTS: Knock-out of the tyrosinase gene in B16F10 led to loss of pigmentation and immature melanosomes. Pigmented tumors contained more M1 and fewer M2 macrophages compared with amelanotic tumors. Bel-sar treatment induced near complete cell death, accompanied with enhanced exposure of DAMPs in both cell lines, resulting in enhanced phagocytosis of BMDMs and maturation of DCs. Bel-sar treatment induced a shift to M1 macrophages and delayed tumor growth in both in vivo tumor models. Following treatment, especially the pigmented tumors and their draining lymph nodes contained IFN-gamma positive CD8+T cells.

CONCLUSIONS: Pigmentation influenced the type of infiltrating macrophages in the tumor, with more M1 macrophages in pigmented tumors. Belzupacap sarotalocan treatment induced immunogenic cell death and tumor growth delay in pigmented as well as in nonpigmented models and stimulated M1 macrophage influx in both models.},
	keywords = {Animals, Macrophages, Melanoma, Mice, Mice, Inbred C57BL, Monophenol Monooxygenase, Pigmentation},
	issn = {1552-5783},
	doi = {10.1167/iovs.65.1.42},
	author = {Ma, Sen and Huis In{\textquoteright}t Veld, Ruben V and Hao, Yang and Gu, Zili and Rich, Cadmus and Gelmi, Maria Chiara and Mulder, Aat A and van Veelen, Peter A and Vu, T H Khanh and van Hall, Thorbald and Ossendorp, Ferry A and Jager, Martine J}
}
@article {1580502,
	title = {A Biomechanical Study of Flanged Intrascleral Haptic Fixation of Three-Piece Intraocular Lenses},
	journal = {Am J Ophthalmol},
	volume = {227},
	year = {2021},
	month = {2021 07},
	pages = {45-52},
	abstract = {PURPOSE: Flanged intrascleral haptic fixation (FISHF) is a useful method for securing intraocular lenses (IOLs) in eyes without capsular support. Biomechanical studies were conducted to support the use of this technique. DESIGN: Laboratory investigation. METHODS: Haptics of 3-piece IOLs were passed through cadaveric human sclera using 30- and 27-gauge needles. Flanges were created by melting 1.0 mm from the haptic ends using cautery. The forces required to remove the flanged haptic from the sclera and disinsert the haptic from the optic were measured using a mechanical tester and a custom-fabricated mount. RESULTS: The mean FISHF dislocation force using 30-gauge needles was greatest with the CT Lucia 602 (2.04 {\textpm} 0.24 newtons [N]) compared to the LI61AO (0.93 {\textpm} 0.41 N; P\&nbsp;=\&nbsp;.001), ZA9003 (0.70 {\textpm} 0.34 N; P\&nbsp;=\&nbsp;\&lt;.001), and MA60AC (0.27 {\textpm} 0.19 N; P \&lt;.001). Using 27-gauge needles with the CT Lucia resulted in a lower dislocation force (0.56 {\textpm} 0.36 N; P \&lt;.001). The FISHF dislocation force was correlated with the flange-to-needle diameter ratio (r\&nbsp;=\&nbsp;0.975). The FISHF dislocation forces of the CT Lucia and LI61AO using 30-gauge needles were not significantly different from their haptic-optic disinsertion forces (P\&nbsp;=\&nbsp;.79 and .27, respectively). There were no differences in flange diameters between 1.0 mm and 2.0 mm haptic melt lengths across the IOLs (P\&nbsp;=\&nbsp;.15-.85). CONCLUSIONS: These data strongly support the biomechanical stability of FISHF with the polyvinylidene fluoride haptics of the CT Lucia using small diameter instruments for the creation of an intrascleral tunnel. 1.0 mm of haptic may be the optimal melt length.},
	keywords = {Biomechanical Phenomena, Humans, Lens Implantation, Intraocular, Lenses, Intraocular, Prosthesis Design, Pseudophakia, Sclera, Suture Techniques, Tissue Donors, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.02.021},
	author = {Ma, Kevin K and Yuan, Amy and Sharifi, Sina and Pineda, Roberto}
}
@article {1593839,
	title = {Ochrobactrum anthropi Keratitis in a Boston Type 1 Keratoprosthesis Recipient},
	journal = {Cornea},
	volume = {40},
	number = {5},
	year = {2021},
	month = {2021 May 01},
	pages = {662-663},
	abstract = {PURPOSE: To report a case of Ochrobactrum anthropi keratitis in an eye with a Boston type 1 keratoprosthesis. METHODS: This is a case report and review of the literature. RESULTS: A 78-year-old man with a history of implantation of a Boston type 1 keratoprosthesis in the left eye presented for a routine follow-up with no acute complaints. In the left eye, visual acuity was 20/60 and slit-lamp examination revealed a 1.5-mm inferotemporal corneal infiltrate adjacent to the optic stem. Corneal cultures grew abundant O. anthropi. After 7 weeks of topical antimicrobial therapy and placement of a temporary tarsorrhaphy, the keratitis resolved. CONCLUSIONS: Ochrobactrum anthropi is an organism associated with indwelling medical devices and can be pathogenic in eyes with implanted keratoprostheses.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002571},
	author = {Ma, Kevin K and Ong Tone, Stephan and Chodosh, James and Saeed, Hajirah N}
}
@article {742276,
	title = {Blockage of PI3K/mTOR Pathways Inhibits Laser-Induced Choroidal Neovascularization and Improves Outcomes Relative to VEGF-A Suppression Alone.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {7},
	year = {2016},
	month = {2016 Jun 1},
	pages = {3138-44},
	abstract = {PURPOSE: Choroidal neovascularization (CNV) is a major cause of visual loss with age-related macular degeneration (AMD). We evaluated whether blockade of phosphatidyl-inositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR), by impairing VEGF-A and other growth factor receptors like platelet-derived growth factor (PDGF), would reduce laser-induced CNV in mice. METHODS: Choroidal neovascularization lesions were induced in C57BL/6 mice. Two groups of mice received oral GSK2126458 (3 mg/kg) or vehicle for 14 days following laser, whereas three groups were treated with GSK2126458 (6 μg/eye), aflibercept (2 μL/eye), or vehicle intravitreally on days 0 and 7 after laser. Vascular leakage was measured by fluorescein angiography (FA) on day 14. Choroidal neovascularization membranes were evaluated on choroidal flat mounts following FITC-dextran perfusion, as well as ED1 and isolectin B4 (IB4) immunohistochemistry. RESULTS: Oral and intravitreal (IVT) GSK2126458 reduced leakage and area of CNV lesions. Greater probability of leaking lesions (\~{}60\%; P \&lt; 0.05) was observed in both vehicle groups. Fluorescein isothiocyanate-dextran-labeled total CNV burden area (total lesion area/eye) was reduced \~{}67\% (P \&lt; 0.05) and 35\% (P = 0.0528) after oral and IVT GSK2126458 administration. GSK2126458 treatment reduced lesion size by \~{}80\% (P \&lt; 0.05) and 50\% (P \&lt; 0.05) for oral and IVT control groups. Aflibercept did not alter lesion size (\~{}27\% reduction). CONCLUSIONS: Phosphatidyl-inositol-3-kinase/mTOR is involved in laser-induced CNV angiogenic processes. GSK2126458 effectively reduces CNV size and leakage. Choroidal neovascularization size following IVT GSK2126458 was smaller than after oral administration. Therefore, inhibition of PI3K/mTOR pathways may be more effective due to blockade of action of multiple growth factors.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18795},
	author = {Ma, Jie and Sun, Yu and L{\'o}pez, Francisco J and Adamson, Peter and Kurali, Edit and Lashkari, Kameran}
}
@article {1528423,
	title = {Dual Molecular Diagnosis of Microsporidia (Encephalitozoon hellem) Keratoconjunctivitis in an Immunocompetent Adult},
	journal = {Cornea},
	volume = {40},
	number = {2},
	year = {2021},
	month = {2021 Feb 01},
	pages = {242-244},
	abstract = {PURPOSE: To report a case of microsporidia (Encephalitozoon hellem) keratoconjunctivitis acquired through avian transmission in an immunocompetent adult, diagnosed by metagenomic deep sequencing (MDS), and confirmed by polymerase chain reaction. METHODS: A case report. RESULTS: An 18-year-old woman was referred with unilateral keratoconjunctivitis unresponsive to topical and systemic therapy after exposure to birdcage debris. Slit-lamp examination of the left eye revealed a follicular papillary reaction of the palpebral conjunctiva and multiple corneal punctate epithelial opacities that stained minimally with fluorescein. In vivo confocal microscopy revealed bright double-walled structures and smaller bright round structures in the superficial epithelial debris and epithelium. Molecular diagnosis with MDS of E. hellem was confirmed by polymerase chain reaction. Clinical resolution and normalization of in vivo confocal microscopy was observed after a 6-week course of topical azithromycin. The patient elected a 3-week course of topical voriconazole 1\% for definitive antimicrosporidial treatment, with no evidence of persistent infection 1 month later. CONCLUSIONS: Microsporidial (E. hellem) keratoconjunctivitis can occur through avian transmission in immunocompetent hosts. Topical azithromycin may be effective against this pathogen. MDS has utility in the diagnosis of atypical keratoconjunctivitis.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002466},
	author = {Ma, Kevin K and Kinde, Benyam and Doan, Thuy and Jacobs, Deborah S and Ong Tone, Stephan}
}
@article {1598043,
	title = {A lateralized model of the pain-depression dyad},
	journal = {Neurosci Biobehav Rev},
	volume = {127},
	year = {2021},
	month = {2021 08},
	pages = {876-883},
	abstract = {Chronic pain and depression are two frequently co-occurring and debilitating conditions. Even though the former is treated as a physical affliction, and the latter as a mental illness, both disorders closely share neural substrates. Here, we review the association of pain with depression, especially when symptoms are lateralized on either side of the body. We also explore the overlapping regions in the forebrain implicated in these conditions. Finally, we synthesize these findings into a model, which addresses gaps in our understanding of comorbid pain and depression. Our lateralized pain-depression dyad model suggests that individuals diagnosed with depression should be closely monitored for pain symptoms in the left hemibody. Conversely, for patients in pain, with the exception of acute pain with a known source, referrals in today{\textquoteright}s pain centers for psychological evaluation should be part of standard practice, within the framework of an interdisciplinary approach to pain treatment.},
	keywords = {Chronic Pain, Depression, Humans},
	issn = {1873-7528},
	doi = {10.1016/j.neubiorev.2021.06.003},
	author = {Maallo, Anne Margarette S and Moulton, Eric A and Sieberg, Christine B and Giddon, Donald B and Borsook, David and Holmes, Scott A}
}
@article {1517212,
	title = {Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis},
	journal = {Stroke},
	volume = {51},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {2018-2025},
	abstract = {BACKGROUND AND PURPOSE: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of \&lt;20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS: We enrolled 112 patients, of whom 25 (22.3\% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1\% of those not treated with alteplase (=0.003) and 11.6\% of those presenting within 4 hours who did not receive alteplase (=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3\%. This favorably compares with a 17.7\% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (=0.01). CONCLUSIONS: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.},
	issn = {1524-4628},
	doi = {10.1161/STROKEAHA.119.028743},
	author = {Mac Grory, Brian and Nackenoff, Alex and Poli, Sven and Spitzer, Martin S and Nedelmann, Max and Guillon, Benoit and Preterre, C{\'e}cile and Chen, Celia S and Lee, Andrew W and Yaghi, Shadi and Stretz, Christoph and Azher, Idrees and Paddock, John and Bakaeva, Tatiana and Greer, David M and Shulman, Julie G and Kowalski, Robert G and Lavin, Patrick and Mistry, Eva and Espaillat, Kiersten and Furie, Karen and Kirshner, Howard and Schrag, Matthew}
}
@article {382606,
	title = {Characterization of large structural genetic mosaicism in human autosomes.},
	journal = {Am J Hum Genet},
	volume = {96},
	number = {3},
	year = {2015},
	month = {2015 Mar 5},
	pages = {487-97},
	abstract = {Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (\&gt;2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total\&nbsp;GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68\%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73\%] individuals). Restricting to events \&gt;2 Mb in size, we observed an increase in event frequency as event\&nbsp;size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5\&nbsp;{\texttimes} 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in\&nbsp;the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2015.01.011},
	author = {Machiela, Mitchell J and Zhou, Weiyin and Sampson, Joshua N and Dean, Michael C and Jacobs, Kevin B and Black, Amanda and Brinton, Louise A and Chang, I-Shou and Chen, Chu and Chen, Constance and Chen, Kexin and Cook, Linda S and Crous Bou, Marta and De Vivo, Immaculata and Doherty, Jennifer and Friedenreich, Christine M and Gaudet, Mia M and Haiman, Christopher A and Hankinson, Susan E and Hartge, Patricia and Henderson, Brian E and Hong, Yun-Chul and Hosgood, H Dean and Hsiung, Chao A and Hu, Wei and Hunter, David J and Jessop, Lea and Kim, Hee Nam and Kim, Yeul Hong and Kim, Young Tae and Klein, Robert and Kraft, Peter and Lan, Qing and Lin, Dongxin and Liu, Jianjun and Le Marchand, Loic and Liang, Xiaolin and Lissowska, Jolanta and Lu, Lingeng and Magliocco, Anthony M and Matsuo, Keitaro and Olson, Sara H and Orlow, Irene and Park, Jae Yong and Pooler, Loreall and Prescott, Jennifer and Rastogi, Radhai and Risch, Harvey A and Schumacher, Fredrick and Seow, Adeline and Setiawan, Veronica Wendy and Shen, Hongbing and Sheng, Xin and Shin, Min-Ho and Shu, Xiao-Ou and Van Den Berg, David and Wang, Jiu-Cun and Wentzensen, Nicolas and Wong, Maria Pik and Wu, Chen and Wu, Tangchun and Wu, Yi-Long and Xia, Lucy and Yang, Hannah P and Yang, Pan-Chyr and Zheng, Wei and Zhou, Baosen and Abnet, Christian C and Albanes, Demetrius and Aldrich, Melinda C and Amos, Christopher and Amundadottir, Laufey T and Berndt, Sonja I and Blot, William J and Bock, Cathryn H and Bracci, Paige M and Burdett, Laurie and Buring, Julie E and Butler, Mary A and Carre{\'o}n, Tania and Chatterjee, Nilanjan and Chung, Charles C and Cook, Michael B and Cullen, Michael and Davis, Faith G and Ding, Ti and Duell, Eric J and Epstein, Caroline G and Fan, Jin-Hu and Figueroa, Jonine D and Fraumeni, Joseph F and Freedman, Neal D and Fuchs, Charles S and Gao, Yu-Tang and Gapstur, Susan M and Pati{\~n}o-Garcia, Ana and Garcia-Closas, Montserrat and Gaziano, J Michael and Giles, Graham G and Gillanders, Elizabeth M and Giovannucci, Edward L and Goldin, Lynn and Goldstein, Alisa M and Greene, Mark H and Hallmans, Goran and Harris, Curtis C and Henriksson, Roger and Holly, Elizabeth A and Hoover, Robert N and Hu, Nan and Hutchinson, Amy and Jenab, Mazda and Johansen, Christoffer and Khaw, Kay-Tee and Koh, Woon-Puay and Kolonel, Laurence N and Kooperberg, Charles and Krogh, Vittorio and Kurtz, Robert C and LaCroix, Andrea and Landgren, Annelie and Landi, Maria Teresa and Li, Donghui and Liao, Linda M and Malats, Nuria and McGlynn, Katherine A and McNeill, Lorna H and McWilliams, Robert R and Melin, Beatrice S and Mirabello, Lisa and Peplonska, Beata and Peters, Ulrike and Petersen, Gloria M and Prokunina-Olsson, Ludmila and Purdue, Mark and Qiao, You-Lin and Rabe, Kari G and Rajaraman, Preetha and Real, Francisco X and Riboli, Elio and Rodr{\'\i}guez-Santiago, Benjam{\'\i}n and Rothman, Nathaniel and Ruder, Avima M and Savage, Sharon A and Schwartz, Ann G and Schwartz, Kendra L and Sesso, Howard D and Severi, Gianluca and Silverman, Debra T and Spitz, Margaret R and Stevens, Victoria L and Stolzenberg-Solomon, Rachael and Stram, Daniel and Tang, Ze-Zhong and Taylor, Philip R and Teras, Lauren R and Tobias, Geoffrey S and Viswanathan, Kala and Wacholder, Sholom and Wang, Zhaoming and Weinstein, Stephanie J and Wheeler, William and White, Emily and Wiencke, John K and Wolpin, Brian M and Wu, Xifeng and Wunder, Jay S and Yu, Kai and Zanetti, Krista A and Zeleniuch-Jacquotte, Anne and Ziegler, Regina G and deAndrade, Mariza and Barnes, Kathleen C and Beaty, Terri H and Bierut, Laura J and Desch, Karl C and Doheny, Kimberly F and Feenstra, Bjarke and Ginsburg, David and Heit, John A and Kang, Jae H and Laurie, Cecilia A and Li, Jun Z and Lowe, William L and Marazita, Mary L and Melbye, Mads and Mirel, Daniel B and Murray, Jeffrey C and Nelson, Sarah C and Pasquale, Louis R and Rice, Kenneth and Wiggs, Janey L and Wise, Anastasia and Tucker, Margaret and P{\'e}rez-Jurado, Luis A and Laurie, Cathy C and Caporaso, Neil E and Yeager, Meredith and Chanock, Stephen J}
}
@article {1125356,
	title = {Therapeutic antibody targeting of Notch3 signaling prevents mural cell loss in CADASIL},
	journal = {J Exp Med},
	volume = {214},
	number = {8},
	year = {2017},
	month = {2017 Aug 07},
	pages = {2271-2282},
	abstract = {Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a neurological syndrome characterized by small vessel disease (SVD), stroke, and vascular cognitive impairment and dementia caused by mutations in NOTCH3 No therapies are available for this condition. Loss of mural cells, which encompass pericytes and vascular smooth muscle cells, is a hallmark of CADASIL and other SVDs, including diabetic retinopathy, resulting in vascular instability. Here, we showed that Notch3 signaling is both necessary and sufficient to support mural cell coverage in arteries using genetic rescue in Notch3 knockout mice. Furthermore, we show that systemic administration of an agonist Notch3 antibody prevents mural cell loss and modifies plasma proteins associated with Notch3 activity, including endostatin/collagen 18α1 and Notch3 extracellular domain in mice with the C455R mutation, a CADASIL variant associated with Notch3 loss of function. These findings open opportunities for the treatment of CADASIL and other SVDs by modulating Notch3 signaling.},
	issn = {1540-9538},
	doi = {10.1084/jem.20161715},
	author = {Machuca-Parra, Arturo I and Bigger-Allen, Alexander A and Sanchez, Angie V and Boutabla, Anissa and Cardona-V{\'e}lez, Jonathan and Amarnani, Dhanesh and Saint-Geniez, Magali and Siebel, Christian W and Kim, Leo A and D{\textquoteright}Amore, Patricia A and Arboleda-Velasquez, Joseph F}
}
@article {541226,
	title = {Failed Cartilaginous Grafts in the Eyelid: A Retrospective Clinicopathological Analysis of 5 Cases.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {5},
	year = {2016},
	month = {2016 Sep-Oct},
	pages = {347-53},
	abstract = {PURPOSE: To analyze the clinical and histopathologic features of 5 failed autologous cartilaginous grafts to the lower eyelids and to analyze the reasons for these failures. METHODS: In this retrospective case series, the data collected included patient ages, reasons for and duration of cartilaginous graft implants, sources of cartilaginous grafts, and clinical and histopathologic findings at time of graft removal using hematoxylin and eosin, elastic, Alcian blue, and Masson trichrome staining for analysis of tissue alterations. RESULTS: Five cartilaginous, posterior lamellar lower eyelid grafts were complicated by eyelid thickening or retraction, graft extrusion, and entropion. Histopathologic findings included segmentation of the original single implant, stripped of its perichondrium, due to "kerfing," sometimes with overlapping of the segments and scar formation between the segments. In place of the perichondrium that had been removed during the preparation the graft implants, a fibrous pseudoperichondrial capsule had formed. Pyknotic nuclei in varying degrees were typically found in the center of the grafts, despite a high degree of preservation of the extracellular matrix (collagenous, elastic, and proteoglycan components). No evidence of inflammation, cartilaginous vascularization, or necrosis was identified in any graft. CONCLUSION: Despite minimal reactive processes, kerfing (partial thickness cuts made in the graft to increase its pliancy) may be partially responsible for graft migration, deformation, and surgical failure. The consequences were graft fragmentation and overlapping of the multiple fragments. Graft migration can be exacerbated if a posterior lamellar graft is used to correct an anterior lamellar deficiency. Interference with the overall architectural integrity of the graft and its extracellular matrix appears to play no role in failure, despite removal of the perichondrium. Mild to moderate degrees of chondrocytic dropout in the absence of necrosis and inflammation are probably attributable to the thick and coarsely textured collagen of the fibrous pseudoperichondrial capsule that may impede diffusion of nutrients into the center of the graft.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000540},
	author = {MacIntosh, Peter W and Jakobiec, Frederick A and Stagner, Anna and Rashid, Alia and Sutula, Francis C and Yoon, Michael K and Fay, Aaron M}
}
@article {1319472,
	title = {Update on the ophthalmic management of facial paralysis},
	journal = {Surv Ophthalmol},
	volume = {64},
	number = {1},
	year = {2019},
	month = {2019 Jan - Feb},
	pages = {79-89},
	abstract = {Bell{\textquoteright}s palsy is the most common neurologic condition affecting the cranial nerves. Lagophthalmos, exposure keratopathy, and corneal ulceration are potential complications. In this review, we evaluate various causes of facial paralysis as well as the level 1 evidence supporting the use of a short course of oral steroids for idiopathic Bell{\textquoteright}s palsy to improve functional outcomes. Various surgical and nonsurgical techniques are also discussed for the management of residual facial dysfunction.},
	keywords = {Disease Management, Facial Paralysis, Humans, Ophthalmology},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2018.06.001},
	author = {MacIntosh, Peter W and Fay, Aaron M}
}
@article {541301,
	title = {High grade neuroendocrine neoplasm of the antrum and orbit.},
	journal = {Surv Ophthalmol},
	volume = {60},
	number = {5},
	year = {2015},
	month = {2015 Sep-Oct},
	pages = {486-94},
	abstract = {Neuroendocrine malignancies-tumors characterized by the production of dense-core secretory granules-are most often encountered in the lungs and can also be found in extrapulmonary sites. Our patient had a primary neuroendocrine tumor of the antrum with an elusive cell of origin that secondarily invaded the inferior orbit. In the sinuses, neuroendocrine tumors may be confused with infectious sinusitis or squamous cell carcinoma. There are no known pathognomonic clinical or radiographic signs to distinguish these tumors from other conditions. Diagnosis depends on a biopsy with histopathologic and immunohistochemical analysis to identify biomarkers such as synaptophysin, chromogranin, CD56 and neuron specific enolase. Our patient{\textquoteright}s tumor defied precise immunohistochemical characterization because of its primitive character and erratic biomarker expression. The diagnosis oscillated between a neuroendocrine carcinoma and an ectopic esthesioneuroblastoma grade IV-hence the use of the more generic nosologic category of neuroendocrine neoplasm without specifying a neuronal or epithelial origin. Data to guide management are limited, particularly in the ophthalmic literature, and derive from experience with tumors of the sinonasal compartments. In the present case of a sino-orbital high grade neuroendocrine neoplasm, regional lymph node metastases developed shortly after presentation. The tumor has responded well to chemotherapy and radiation, but recurrence is often encountered within 2 years in this class of neoplasms.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2015.03.002},
	author = {MacIntosh, Peter W and Jakobiec, Frederick A and Stagner, Anna M and Gilani, Sapideh and Fay, Aaron}
}
@article {1638561,
	title = {Immunogenicity of an AAV-Based COVID-19 Vaccine in Murine Models of Obesity and Aging},
	journal = {Viruses},
	volume = {14},
	number = {4},
	year = {2022},
	month = {2022 Apr 15},
	abstract = {The SARS-CoV-2 pandemic has had a disastrous impact on global health. Although some vaccine candidates have been effective in combating SARS-CoV-2, logistical, economical, and sociological aspects still limit vaccine access globally. Recently, we reported on two room-temperature stable AAV-based COVID-19 vaccines that induced potent and protective immunogenicity following a single injection in murine and primate models. Obesity and old age are associated with increased mortality in COVID-19, as well as reduced immunogenicity and efficacy of vaccines. Here, we investigated the effectiveness of the AAVCOVID vaccine candidates in murine models of obesity and aging. Results demonstrate that obesity did not significantly alter the immunogenicity of either vaccine candidate. In aged mice, vaccine immunogenicity was impaired. These results suggest that AAV-based vaccines may have limitations in older populations and may be equally applicable in obese and non-obese populations.},
	keywords = {Aged, Aging, Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Vaccines, Disease Models, Animal, Humans, Mice, Obesity, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vaccines},
	issn = {1999-4915},
	doi = {10.3390/v14040820},
	author = {Maciorowski, Dawid and Diop, Cheikh and Bhatt, Urja and Estelien, Reynette and Dan Li and Chauhan, Ruchi and Vandenberghe, Luk H and Zabaleta, Nerea}
}
@article {1363148,
	title = {Improving ophthalmic outcomes in children with unilateral coronal synostosis by treatment with endoscopic strip craniectomy and helmet therapy rather than fronto-orbital advancement},
	journal = {J AAPOS},
	volume = {17},
	number = {3},
	year = {2013},
	month = {2013 Jun},
	pages = {259-65},
	abstract = {PURPOSE: To compare long-term ophthalmic outcomes in infants treated for unilateral coronal synostosis (UCS) by endoscopic strip craniectomy (ESC) and helmet therapy with those treated by fronto-orbital advancement (FOA). METHODS: Consecutive patients with UCS, uncomplicated by other suture synostosis, were identified by a retrospective review of medical records. Assessment of presence of amblyopia, cycloplegic refraction, strabismus, and strabismus surgical intervention at all visits was recorded. RESULTS: Between 2004 and 2010, 22 patients were treated by FOA (mean follow-up, 21.5 months) and 21 patients with ESC and helmet therapy (mean follow-up, 23.5 months). The mean aniso-astigmatism was equal; however, the SD was greater for those treated by FOA (P \&lt; 0.05). A more severe pattern of strabismus developed in those treated by FOA (P \&lt; 0.0001). Those treated by FOA were more likely to have amblyopia (P = 0.0015) and to undergo surgical correction of their strabismus (odds ratio, 6.3:1). CONCLUSIONS: Children with UCS treated with ESC and helmeting had less severe overelevation in adduction, amblyopia, extremes of astigmatism, and less need for strabismus surgery than those treated by FOA. Although the reason for these more favorable outcomes remains uncertain, we speculate that the earlier timing of ESC or differences in the anatomical changes resulting from the two procedures may play a role.},
	keywords = {Amblyopia, Cranial Sutures, Craniosynostoses, Craniotomy, Endoscopy, Eye Movements, Follow-Up Studies, Head Protective Devices, Humans, Infant, Ophthalmologic Surgical Procedures, Postoperative Complications, Retrospective Studies, Strabismus, Tomography, X-Ray Computed, Treatment Outcome, Vision, Binocular},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2013.01.009},
	author = {MacKinnon, Sarah and Proctor, Mark R and Rogers, Gary F and Meara, John G and Whitecross, Sarah and Dagi, Linda R}
}
@article {313246,
	title = {Diagnostic distinctions and genetic analysis of patients diagnosed with moebius syndrome},
	journal = {Ophthalmology},
	volume = {121},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {1461-8},
	abstract = {OBJECTIVE: To improve diagnostic assessment in Moebius syndrome by (1) creating more selective diagnostic subgroups and (2) conducting genetic evaluation in a large patient cohort. DESIGN: Prospective, observational study. PARTICIPANTS: Attendees of 3 consecutive Moebius syndrome conferences held in the United States, with a prior diagnosis of Moebius syndrome, were invited to participate. METHODS: Participants underwent standardized ophthalmologic examination for Moebius syndrome minimum diagnostic criteria (MDC) (congenital, nonprogressive facial palsy, and abduction deficit) and genetic testing for HOXA1, HOXB1, and TUBB3 mutations. MAIN OUTCOME MEASURES: The number of patients meeting MDC and the number of patients with confirmed genetic mutation. RESULTS: A total of 112 participants from 107 families enrolled. Nineteen percent of participants (21/112) did not meet accepted MDC for Moebius syndrome because they had abduction deficits without facial palsy or facial palsy with full ocular motility. All 5 families with 2 affected individuals had at least 1 family member in this category, including 2 siblings with comitant strabismus who harbored a HOXB1 mutation. Four unrelated participants, also not meeting MDC, had large-angle exotropia, vertical gaze deficiency, and ptosis consistent with congenital fibrosis of the extraocular muscles type 3 (CFEOM3); 1 patient harbored a novel TUBB3 mutation, and 3 patients harbored previously reported de novo TUBB3 mutations. Three percent of participants (3/112) met MDC but also had restricted vertical gaze. The remaining 88 participants (79\%) met MDC and had full vertical gaze. This group had relatively homogeneous findings, and none had a family history of Moebius syndrome. Two previously undescribed phenomena were observed in this category: (1) volitional Bell{\textquoteright}s phenomenon and (2) intorsion with fixation. CONCLUSIONS: Although the genetic contributors to classic Moebius syndrome remain elusive, accuracy in clinical evaluation will properly subdivide patients to facilitate genetic testing as new candidate genes are identified. Failure to test ocular motility may lead to misdiagnosis of Moebius syndrome, especially in patients who have facial palsy with full ductions. Patients with exotropia, vertical gaze limitation, and ptosis do not have classic Moebius syndrome and may have TUBB3 mutations associated with CFEOM3. To optimize genetic analysis, we propose adding "full vertical motility" to the MDC for Moebius syndrome.},
	keywords = {Adolescent, Adult, Blepharoptosis, Child, Child, Preschool, DNA Mutational Analysis, Exotropia, Eye Diseases, Hereditary, Eye Movements, Female, Fibrosis, Homeodomain Proteins, Humans, Infant, Male, Middle Aged, Mobius Syndrome, Mutation, Ocular Motility Disorders, Polymerase Chain Reaction, Prospective Studies, Transcription Factors, Tubulin, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.01.006},
	author = {MacKinnon, Sarah and Oystreck, Darren T and Andrews, Caroline and Chan, Wai-Man and Hunter, David G and Engle, Elizabeth C}
}
@article {1798516,
	title = {Applications of artificial intelligence-enabled robots and chatbots in ophthalmology: recent advances and future trends},
	journal = {Curr Opin Ophthalmol},
	volume = {35},
	number = {3},
	year = {2024},
	month = {2024 May 01},
	pages = {238-243},
	abstract = {PURPOSE OF REVIEW: Recent advances in artificial intelligence (AI), robotics, and chatbots have brought these technologies to the forefront of medicine, particularly ophthalmology. These technologies have been applied in diagnosis, prognosis, surgical operations, and patient-specific care in ophthalmology. It is thus both timely and pertinent to assess the existing landscape, recent advances, and trajectory of trends of AI, AI-enabled robots, and chatbots in ophthalmology.

RECENT FINDINGS: Some recent developments have integrated AI enabled robotics with diagnosis, and surgical procedures in ophthalmology. More recently, large language models (LLMs) like ChatGPT have shown promise in augmenting research capabilities and diagnosing ophthalmic diseases. These developments may portend a new era of doctor-patient-machine collaboration.

SUMMARY: Ophthalmology is undergoing a revolutionary change in research, clinical practice, and surgical interventions. Ophthalmic AI-enabled robotics and chatbot technologies based on LLMs are converging to create a new era of digital ophthalmology. Collectively, these developments portend a future in which conventional ophthalmic knowledge will be seamlessly integrated with AI to improve the patient experience and enhance therapeutic outcomes.},
	keywords = {Artificial Intelligence, Humans, Ophthalmology, Robotics},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000001035},
	author = {Madadi, Yeganeh and Delsoz, Mohammad and Khouri, Albert S and Boland, Michael and Grzybowski, Andrzej and Yousefi, Siamak}
}
@article {1405414,
	title = {Neural Interactions Underlying Visuomotor Associations in the Human Brain},
	journal = {Cereb Cortex},
	volume = {29},
	number = {11},
	year = {2019},
	month = {2019 Dec 17},
	pages = {4551-4567},
	abstract = {Rapid and flexible learning during behavioral choices is critical to our daily endeavors and constitutes a hallmark of dynamic reasoning. An important paradigm to examine flexible behavior involves learning new arbitrary associations mapping visual inputs to motor outputs. We conjectured that visuomotor rules are instantiated by translating visual signals into actions through dynamic interactions between visual, frontal and motor cortex. We evaluated the neural representation of such visuomotor rules by performing intracranial field potential recordings in epilepsy subjects during a rule-learning delayed match-to-behavior task. Learning new visuomotor mappings led to the emergence of specific responses associating visual signals with motor outputs in 3 anatomical clusters in frontal, anteroventral temporal and posterior parietal cortex. After learning, mapping selective signals during the delay period showed interactions with visual and motor signals. These observations provide initial steps towards elucidating the dynamic circuits underlying flexible behavior and how communication between subregions of frontal, temporal, and parietal cortex leads to rapid learning of task-relevant choices.},
	issn = {1460-2199},
	doi = {10.1093/cercor/bhy333},
	author = {Madhavan, Radhika and Bansal, Arjun K and Madsen, Joseph R and Golby, Alexandra J and Tierney, Travis S and Eskandar, Emad N and Anderson, William S and Kreiman, Gabriel}
}
@article {1645467,
	title = {The Association of Female Reproductive Factors with Glaucoma and Related Traits: A Systematic Review},
	journal = {Ophthalmol Glaucoma},
	volume = {5},
	number = {6},
	year = {2022},
	month = {2022 Nov-Dec},
	pages = {628-647},
	abstract = {TOPIC: This systematic review summarizes evidence for associations between female reproductive factors (age at menarche, parity, oral contraceptive [OC] use, age at menopause, and postmenopausal hormone [PMH] use) and intraocular pressure (IOP) or open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding the associations between female reproductive factors and glaucoma may shed light on the disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable, which may lead to new therapies. METHODS: Two reviewers independently extracted articles in MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects aged \&gt; 18 years; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional, or randomized controlled trial design; a reported measure of association, such as the hazard ratio, relative risk, odds ratio, or mean difference, with an associated confidence interval; and a measured exposure of at least 1 of the following variables: age at menarche, parity, OC use, age at menopause, or PMH use. RESULTS: We included a total of 27 studies. Substantial differences in study designs, exposure and treatment levels, treatment durations, and variable reporting precluded a meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and a lower IOP were identified. Estrogen-only PMH use may be associated with lower OAG risk, which may be modified by race. No significant associations were found with combined estrogen-and-progesterone PMH use. No strong associations between parity or age at menarche and glaucoma were found, but a younger age at menopause was associated with an increased glaucoma risk, and adverse associations were identified with a longer duration of OC use, though no overall association with OC use was found. CONCLUSIONS: The association between PMH use and lower IOP or OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. Future research should examine associations with IOP specifically and how the relationship between genetic factors and OAG risks may be influenced by female reproductive factors.},
	keywords = {Cross-Sectional Studies, Estrogens, Female, Glaucoma, Glaucoma, Open-Angle, Humans, Pregnancy, Systematic Reviews as Topic},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.06.003},
	author = {Madjedi, Kian M and Stuart, Kelsey V and Chua, Sharon Y L and Foster, Paul J and Strouthidis, Nicholas G and Luben, Robert N and Warwick, Alasdair N and Kang, Jae H and Wiggs, Janey L and Pasquale, Louis R and Khawaja, Anthony P}
}
@article {1653584,
	title = {The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts},
	journal = {Ophthalmology},
	volume = {129},
	number = {9},
	year = {2022},
	month = {2022 09},
	pages = {986-996},
	abstract = {PURPOSE: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). DESIGN: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. PARTICIPANTS: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and\&nbsp;2009. METHODS: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). MAIN OUTCOME MEASURES: Corneal-compensated IOP. RESULTS: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95\% confidence interval [CI], 0.06-0.11 mmHg; P \&lt; 0.001), 0.11 mmHg (95\% CI, 0.08-0.13 mmHg; P \&lt; 0.001), and 0.07 mmHg (95\% CI, 0.05-0.09 mmHg; P \&lt; 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95\% CI, 0.07-0.31 mmHg; P\&nbsp;= 0.001), 0.14 mmHg (95\% CI, 0.03-0.25 mmHg; P\&nbsp;= 0.016), and 0.17 mmHg (95\% CI, 0.06-0.29 mmHg; P\&nbsp;= 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (-0.05 mmHg; 95\% CI, -0.08 to -0.03; P\&nbsp;\&lt;\&nbsp;0.001) was not replicated in the EPIC-Norfolk cohort (P\&nbsp;= 0.30). CONCLUSIONS: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.},
	keywords = {Aged, Cholesterol, HDL, Cholesterol, LDL, Cross-Sectional Studies, Humans, Intraocular Pressure, Middle Aged, Prospective Studies, Risk Factors, Triglycerides, United Kingdom},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.04.023},
	author = {Madjedi, Kian M and Stuart, Kelsey V and Chua, Sharon Y L and Luben, Robert N and Warwick, Alasdair and Pasquale, Louis R and Kang, Jae H and Wiggs, Janey L and Lentjes, Marleen Ah and Aschard, Hugues and Sattar, Naveed and Foster, Paul J and Khawaja, Anthony P and Modifiable Risk Factors for Glaucoma Collaboration and the UK Biobank Eye and Vision Consortium}
}
@article {1709741,
	title = {The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank},
	journal = {Ophthalmology},
	volume = {130},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {1024-1036},
	abstract = {PURPOSE: To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal relationships using Mendelian randomization (MR). DESIGN: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. PARTICIPANTS: UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n\&nbsp;= 94 206 and n\&nbsp;= 27 777, respectively), macular inner retinal OCT measurements (n\&nbsp;=\&nbsp;36 274 and n\&nbsp;= 9991, respectively), and glaucoma status (n\&nbsp;= 86 803 and n\&nbsp;= 23 556, respectively). METHODS: We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene-PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma. MAIN OUTCOME MEASURES: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and glaucoma status. RESULTS: In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P \&lt; 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by\&nbsp;+0.57 μm (P \&lt; 0.001) and\&nbsp;+0.42 μm (P\&nbsp;= 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of\&nbsp;+0.08 mmHg (P\&nbsp;= 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome. CONCLUSIONS: Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Biological Specimen Banks, Cross-Sectional Studies, Glaucoma, Humans, Intraocular Pressure, Macula Lutea, Mendelian Randomization Analysis, Retinal Ganglion Cells, Tomography, Optical Coherence, United Kingdom},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.06.009},
	author = {Madjedi, Kian M and Stuart, Kelsey V and Chua, Sharon Y L and Ramulu, Pradeep Y and Warwick, Alasdair and Luben, Robert N and Sun, Zihan and Chia, Mark A and Aschard, Hugues and Wiggs, Janey L and Kang, Jae H and Pasquale, Louis R and Foster, Paul J and Khawaja, Anthony P and Modifiable Risk Factors for Glaucoma Collaboration and the UK Biobank Eye and Vision Consortium}
}
@article {1328895,
	title = {An update of idiopathic intracranial hypertension},
	journal = {Curr Opin Ophthalmol},
	volume = {29},
	number = {6},
	year = {2018},
	month = {2018 Nov},
	pages = {495-502},
	abstract = {PURPOSE OF REVIEW: We aim to provide a comprehensive and updated review on idiopathic intracranial hypertension (IIH), including the most current studies and treatment options. Special focus will be put on recent theories about the pathophysiology, and on newer prospective studies on treatment modalities. RECENT FINDINGS: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) provided evidence supporting acetazolamide as a well tolerated first-line therapy in IIH patients with mild vision loss. Recent studies have shown venous sinus stenting as a well tolerated and effective surgical alternative for patients with refractory IIH. SUMMARY: Idiopathic intracranial hypertension is a vision-threatening disorder that predominantly affects obese women of childbearing age. This disorder is becoming more prevalent as the obesity epidemic continues to increase. As our understanding of this disorder continues to evolve, diagnosis and management approaches have changed over time. However, the pathogenesis for IIH remains unclear. Several theories have been proposed, including abnormalities in cerebrospinal dynamics, metabolic causes and genetics. The diagnostic criteria are based on the revised Dandy criteria. Traditionally, treatment was based on clinical experiences and retrospective studies. However, a new, prospective, randomized, controlled trial, the IIHTT, provided evidence-based data to help guide medical therapy. Additionally new, prospective studies are underway for the different surgical alternatives to treat IIH.},
	keywords = {Acetazolamide, Carbonic Anhydrase Inhibitors, Humans, Intracranial Pressure, Papilledema, Pseudotumor Cerebri},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000518},
	author = {Madriz Peralta, Gabriela and Cestari, Dean M}
}
@article {1748346,
	title = {Influence of prismatic effect due to decentration of optical center in ophthalmic lens},
	journal = {Health Sci Rep},
	volume = {6},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {e1472},
	abstract = {BACKGROUND AND AIMS: Induced prismatic effects due to poor fitting spectacle frames is a common problem, seen in most of the spectacle wearers and this improper fitting is often due to optical center demarcation on lenses and this error causes asthenopic symptoms and diplopia. However, these errors are most common in developing countries due to lack of awareness, hence a standardized regulation is required. The current study aimed to estimate the amount of prismatic effect that is induced due to the decentration of an optical center in ophthalmic lens. METHODS: A quantitative cross-sectional study was conducted in single vision spectacle wearers (N = 120) with a mean age of 25 {\textpm} 5 years. The pupillometric evaluation was performed to mark the pupil center on the spectacle lens. A lensometry evaluation was done to mark the optic center of the spectacle lens. A comparison was made to note whether the optic center is aligned with pupillary center. Objective assessment was performed through Prentice{\textquoteright}s rule (P = cF) and subjective symptoms were assessed through a validated visual comfort questionnaire. RESULTS: In this sample, around 57\% of the individual with single vision glasses were not looking through the optic center and experiencing induced prismatic effect of -0.7 to 0.6 prism diopter, with mean decentration of 3.5 mm. Forty percent of the individuals with misaligned optic center showed asthenopic symptoms and visual discomfort. CONCLUSION: Optometrist should check quality of dispensing and visual performance before handing over the newly dispensed glasses to the patients.},
	issn = {2398-8835},
	doi = {10.1002/hsr2.1472},
	author = {Madrolu, Vijay Sandeep Kumar and Male, Shiva Ram and Bhardwaj, Rishi and Theagarayan, Baskar}
}
@article {1688296,
	title = {Hot towels: The bedrock of Meibomian gland dysfunction treatment - A review},
	journal = {Cont Lens Anterior Eye},
	volume = {46},
	number = {2},
	year = {2023},
	month = {2023 Apr},
	pages = {101775},
	abstract = {BACKGROUND: Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed. PURPOSE: To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment. METHODS: Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR "dry eye" OR DED). All relevant original articles with English full-text were included. RESULTS: The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40\&nbsp;{\textdegree}C and 47\&nbsp;{\textdegree}C. Towels heated to around 45\&nbsp;{\textdegree}C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies. CONCLUSION: Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this.},
	keywords = {Dry Eye Syndromes, Eyelid Diseases, Hot Temperature, Humans, Hyperthermia, Induced, Meibomian Gland Dysfunction, Meibomian Glands, Tears},
	issn = {1476-5411},
	doi = {10.1016/j.clae.2022.101775},
	author = {Magno, Morten Schjerven and Olafsson, Jonatan and Beining, Marie and Moschowits, Emily and Lagali, Neil and Wolffsohn, James S and Craig, Jennifer P and Vehof, Jelle and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1623345,
	title = {Chambered warm moist air eyelid warming devices - a review},
	journal = {Acta Ophthalmol},
	year = {2021},
	month = {2021 Nov 08},
	abstract = {BACKGROUND: Eyelid warming is an important treatment for meibomian gland dysfunction (MGD). Specialized chambered devices, using warm moist air have been developed. PURPOSE: To critically evaluate the literature on the safety and efficacy of chambered warm moist air devices in MGD treatment and pinpoint areas of future research. METHODS: PubMed and Embase were searched on 06 June 2021. The search term was {\textquoteright}(warm OR heat OR steam OR goggle OR spectacle OR moist air) AND (meibomian OR MGD OR blepharitis OR eyelid OR dry eye OR DED){\textquoteright}. All relevant articles with available English full text were included. RESULTS: Eighteen articles assessing the application of chambered warm moist air eyelid warming devices were identified. In single-application studies, steam-based eyelid warming increased the eyelid temperature and improved symptoms, lipid layer thickness, and tear film breakup time (TBUT). In treatment studies, the steam-based devices improved TBUT and symptom scores. However, in the only randomized controlled trial (RCT) comparing chambered steam-based heat to hot towel treatment, there was no difference between groups for the primary outcome measure; the proportion of subjects noting symptom improvement after 4 weeks. CONCLUSION: Currently available chambered warm moist air eyelid warming devices are safe and effective at raising eyelid temperature to therapeutic levels and improving signs and symptoms of dry eye. However, it is not clear if they provide a greater benefit than other eyelid warming therapies. Further well-conducted RCTs comparing moist and dry heat devices should be conducted on patients across the range of DED severities and subtype spectrum.},
	issn = {1755-3768},
	doi = {10.1111/aos.15052},
	author = {Magno, Morten Schjerven and Olafsson, Jonatan and Beining, Marie and Moschowits, Emily and Lagali, Neil and Wolffsohn, James S and Craig, Jennifer P and Dartt, Darlene A. and Vehof, Jelle and Utheim, Tor P}
}
@article {1619430,
	title = {Lapses in Care Among Patients Assigned to Ranibizumab for Proliferative Diabetic Retinopathy: A Post Hoc Analysis of a Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {12},
	year = {2021},
	month = {2021 Dec 01},
	pages = {1266-1273},
	abstract = {Importance: The follow-up schedule for individuals with eyes treated with anti-vascular endothelial growth factor agents for proliferative diabetic retinopathy (PDR) requires that patients return frequently for monitoring and repeated treatment. The likelihood that a patient will comply should be a consideration in choosing a treatment approach. Objective: To describe completion of scheduled examinations among participants assigned to intravitreous injections of ranibizumab for PDR in a multicenter randomized clinical trial. Design, Setting, and Participants: This post hoc analysis evaluates data from a randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012. Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. Data were analyzed from April 2019 to July 2021. Interventions: Ranibizumab injections for PDR or macular edema. Main Outcomes and Measures: A long lapse in care of 8 or more weeks past a scheduled examination, dropout from follow-up, visual acuity at 5 years. Results: Among 170 participants, the median age was 51 years, and 44.7\% were female. Through 5 years of follow-up, 94 of 170 participants (55.3\%) had 1 or more long lapse in care. Median time to the first long lapse was 210 weeks, and 69 of 94 participants (73.4\%) returned for examination after the first long lapse. Fifty of 170 participants (29.4\%) dropped out of follow-up by 5 years. Among the 120 participants who completed the 5-year examination, median change from baseline in visual acuity was -2 letters for participants who had 1 or more long lapse compared with +5 letters for those without a long lapse (P = .02). After multivariable adjustment, the odds ratio (95\% CI) for baseline associations with 1 or more long lapse was 1.21 (1.03-1.43) for each 5-letter decrement in visual acuity score, 2.19 (1.09-4.38) for neovascularization of the disc and elsewhere, and 3.48 (1.38-8.78) for no prior laser treatment for diabetic macular edema. Conclusions and Relevance: Over 5 years, approximately half of the participants assigned to ranibizumab for PDR had a long lapse in care despite substantial effort by the DRCR Retina Network to facilitate timely completion of examinations. The likelihood of a long lapse in care during long-term follow-up needs to be considered when choosing treatment for PDR. Trial Registration: ClinicalTrials.gov Identifier: NCT01489189.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.4103},
	author = {Maguire, Maureen G and Liu, Danni and Bressler, Susan B and Friedman, Scott M and Melia, Michele and Stockdale, Cynthia R and Glassman, Adam R and Sun, Jennifer K and DRCR Retina Network}
}
@article {1638569,
	title = {Clinical and neuroradiologic characteristics in varicella zoster virus reactivation with central nervous system involvement},
	journal = {J Neurol Sci},
	volume = {437},
	year = {2022},
	month = {2022 Jun 15},
	pages = {120262},
	abstract = {OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) characteristics of patients with varicella zoster virus (VZV) reactivation involving the cranial nerves and central nervous system (CNS). METHODS: This is a retrospective, multi-center case-series of 37 patients with VZV infection affecting the cranial nerves and CNS. RESULTS: The median age was 71\&nbsp;years [IQR 51.5-76]; 21 (57\%) were men. Cerebrospinal fluid (CSF) was available in 24/37 (65\%); median CSF white blood cell count was 11 [IQR 2-23] cells/μL and protein was 45.5 [IQR 34.5-75.5] mg/dL. VZV polymerase chain reaction (PCR) assays were positive in 6/21 (29\%) CSF and 8/9 (89\%) ocular samples. Clinical involvement included the optic nerve in 12 (32\%), other cranial nerves in 20 (54\%), brain parenchyma in 12 (32\%) and spinal cord or nerve roots in 4 (11\%). Twenty-seven/28 immunocompetent patients{\textquoteright} MRIs were available for review (96\%). Of the 27, 18 had T1 postcontrast fat saturated sequences without motion artifact to evaluate for cranial nerve enhancement and optic perineuritis (OPN). Eight/18 (44\%) demonstrated OPN. All 8 experienced vision loss: 3 optic neuritis, 1 acute retinal necrosis, and 3 CNS vasculitis with 1 central and 1 branch retinal artery occlusion and 1 uveitis. Diplopic patients had cranial nerve and cavernous sinus enhancement. All immunosuppressed patients were imaged. Seven/9 (88\%) had extensive neuraxis involvement, including encephalitis, vasculitis and transverse myelitis; one case had OPN. CONCLUSION: OPN is a frequent manifestation in VZV-associated vision loss among immunocompetent patients. Immunosuppressed patients had greater neuraxis involvement. Optimizing MRI protocols may improve early diagnosis in VZV reactivation.},
	keywords = {Aged, Central Nervous System, Encephalitis, Encephalitis, Varicella Zoster, Female, Herpes Zoster, Herpesvirus 3, Human, Humans, Male, Polymerase Chain Reaction, Retrospective Studies},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2022.120262},
	author = {Maher, Mary D and Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Collens, Sarah I and Gilbert, Aubrey L and Torun, Nurhan and Klein, Joshua P and Sobrin, Lucia and Buchbinder, Bradley R and Rajiv Gupta and Mukerji, Shibani S and Chwalisz, Bart K}
}
@article {1677741,
	title = {Most Common Ophthalmic Diagnoses in Eye Emergency Departments: A Multicenter Study},
	journal = {Am J Ophthalmol},
	volume = {254},
	year = {2023},
	month = {2023 Oct},
	pages = {36-43},
	abstract = {PURPOSE: To characterize the most common ophthalmic conditions seen in the emergency department (ED) DESIGN: Cross-sectional study METHODS: This is a multicenter study of 64,988 patients who visited the Bascom Palmer Eye Institute, Massachusetts Eye and Ear, Wills Eye Hospital, and Johns Hopkins Hospital/Wilmer Eye Institute from January 1, 2019, until December 31, 2019. Demographic and primary diagnosis data were extracted including gender, age, race, ethnicity, insurance type, and ophthalmology consult status. Descriptive statistics were performed on all data using STATA IC 14 (64-bit). RESULTS: A total of 64,988 patients with primary ocular diagnoses were seen across all 4 EDs. The majority of patients were White (63.1\%), non-Hispanic/Latino (64.8\%), and female (52.3\%). The most frequently seen age group was 50-64 years (28.6\%). The most common diagnoses across all institutions were conjunctivitis (7.91\%), corneal abrasions (5.61\%), dry eye (4.49\%), posterior vitreous detachments (4.15\%), chalazions (3.71\%), corneal ulcers (3.01\%), subconjunctival hemorrhages (2.96\%), corneal foreign bodies (2.94\%), retinal detachments (2.51\%), and glaucoma (2.12\%). Specifically, viral conjunctivitis (2283 of 5139, 44.4\%) and primary open-angle glaucoma (382 of 1379, 27.7\%) were the most frequently seen subtypes of conjunctivitis and glaucoma. CONCLUSIONS: The most regularly treated ophthalmic conditions in high-volume EDs tend to be lower acuity diagnoses. To combat ED overcrowding and rising health care costs in the United States, we suggest diverting eye-related ED visits to a specialized eye ED service or same-day eye clinic appointment in addition to expanding education for patients and primary care clinicians.},
	keywords = {Conjunctivitis, Cross-Sectional Studies, Emergency Service, Hospital, Female, Glaucoma, Glaucoma, Open-Angle, Humans, Middle Aged, United States},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.03.016},
	author = {Mahjoub, Heba and Ssekasanvu, Joseph and Yonekawa, Yoshihiro and Justin, Grant A and Cavuoto, Kara M and Lorch, Alice and Madan, Vrinda and Sivakumar, Ishwarya and Zhao, Xiyu and Quintero, Michael and Simeon, Olivia Febles and Salabati, Mirataollah and Wu, Connie M and Woreta, Fasika A}
}
@article {1109851,
	title = {Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Jun 13},
	pages = {3375},
	abstract = {Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress. Gene silencing also revealed that Snail enhanced the permeability of endothelial monolayers to macromolecules by promoting EC proliferation and migration. En face staining of the murine aorta or carotid arteries modified with flow-altering cuffs demonstrated that Snail was expressed preferentially at low shear stress sites that are predisposed to atherosclerosis. Snail was also expressed in EC overlying atherosclerotic plaques in coronary arteries from patients with ischemic heart disease implying a role in human arterial disease. We conclude that Snail is an essential driver of EndMT under low shear stress conditions and may promote early atherogenesis by enhancing vascular permeability.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-03532-z},
	author = {Mahmoud, Marwa M and Serbanovic-Canic, Jovana and Feng, Shuang and Souilhol, Celine and Xing, Rouyu and Hsiao, Sarah and Mammoto, Akiko and Chen, Jing and Ariaans, Markus and Francis, Sheila E and Van der Heiden, Kim and Ridger, Victoria and Evans, Paul C}
}
@article {1490446,
	title = {Author Correction: Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Feb 26},
	pages = {3870},
	abstract = {An amendment to this paper has been published and can be accessed via a link at the top of the paper.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-60955-x},
	author = {Mahmoud, Marwa M and Serbanovic-Canic, Jovana and Feng, Shuang and Souilhol, Celine and Xing, Rouyu and Hsiao, Sarah and Mammoto, Akiko and Chen, Jing and Ariaans, Markus and Francis, Sheila E and Van der Heiden, Kim and Ridger, Victoria and Evans, Paul C}
}
@article {1667719,
	title = {Combined Microinvasive Glaucoma Surgery - A Review of the Literature and Future Directions},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {6},
	year = {2023},
	month = {2023 Aug},
	pages = {529-536},
	abstract = {The use of microinvasive invasive glaucoma surgery (MIGS) in the treatment of glaucoma has increased exponentially over the last 10 years. However, practice patterns vary widely given the relative newness of these technologies. Some surgeons perform two or more MIGS simultaneously, such as those that target aqueous production and those that target aqueous outflow. These combined MIGS (cMIGS) may result in lower intraocular pressure (IOP) and reduced medication burden as compared to single MIGS (sMIGS). Current evidence suggests some cMIGS are more effective in reducing medication burden for at least 12\&nbsp;months versus sMIGS. This review focuses on the current evidence related to the efficacy of cMIGS as well as novel combinations of standalone MIGS, limitations of the current literature, and future directions for research.},
	keywords = {Glaucoma, Glaucoma Drainage Implants, Humans, Intraocular Pressure, Ophthalmologic Surgical Procedures, Tonometry, Ocular},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2181665},
	author = {Mai, Derek D and Ingram, Zoe and Oberfeld, Blake and Sol{\'a}-Del Valle, David}
}
@article {1789161,
	title = {Peripheral monocytes and neutrophils promote photoreceptor cell death in an experimental retinal detachment model},
	journal = {Cell Death Dis},
	volume = {14},
	number = {12},
	year = {2023},
	month = {2023 Dec 16},
	pages = {834},
	abstract = {Photoreceptor cell death and immune cell infiltration are two major events that contribute to retinal degeneration. However, the relationship between these two events has not been well delineated, primarily because of an inadequate understanding of the immunological processes involved in photoreceptor degeneration, especially that of peripheral leukocytes that infiltrate the subretinal space and retinal tissues. In this work, we characterized the role of leukocyte infiltration within the detached retina. We observed that CD45+ CD11b+ Ly6G+ neutrophils and CD45+ CD11b+ Ly6G- Ly6C+ monocytes are the predominant peripheral immune cell populations that infiltrate the retinal and subretinal space after detachment. Selective depletion of monocytes or neutrophils using cell-specific targeting is neuroprotective for photoreceptors. These results indicate that peripheral innate immune cells contribute to photoreceptor degeneration, and targeting these immune cell populations could be therapeutic during retinal detachment.},
	keywords = {Animals, Disease Models, Animal, Humans, Monocytes, Neutrophils, Photoreceptor Cells, Photoreceptor Cells, Vertebrate, Retina, Retinal Degeneration, Retinal Detachment},
	issn = {2041-4889},
	doi = {10.1038/s41419-023-06350-6},
	author = {Maidana, Daniel E and Gonzalez-Buendia, Lucia and Pastor-Puente, Sara and Naqvi, Afsar and Paschalis, Eleftherios and Kazlauskas, Andrius and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1538325,
	title = {ThicknessTool: automated ImageJ retinal layer thickness and profile in digital images},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Oct 28},
	pages = {18459},
	abstract = {To develop an automated retina layer thickness measurement tool for the ImageJ platform, to quantitate nuclear layers following the retina contour. We developed the ThicknessTool (TT), an automated thickness measurement plugin for the ImageJ platform. To calibrate TT, we created a calibration dataset of mock binary skeletonized mask images with increasing thickness masks and different rotations. Following, we created a training dataset and performed an agreement analysis of thickness measurements between TT and two masked manual observers. Finally, we tested the performance of TT measurements in a validation dataset of retinal detachment images. In the calibration dataset, there were no differences in layer thickness between measured and known thickness masks, with an overall coefficient of variation of 0.00\%. Training dataset measurements of immunofluorescence retina nuclear layers disclosed no significant differences between TT and any observer{\textquoteright}s average outer nuclear layer (ONL) (p = 0.998), inner nuclear layer (INL) (p = 0.807), and ONL/INL ratio (p = 0.944) measurements. Agreement analysis showed that bias between TT vs. observers{\textquoteright} mean was lower than between any observers{\textquoteright} mean against each other in the ONL (0.77 {\textpm} 0.34\&nbsp;{\textmu}m vs 3.25 {\textpm} 0.33\&nbsp;{\textmu}m) and INL (1.59 {\textpm} 0.28\&nbsp;{\textmu}m vs 2.82 {\textpm} 0.36\&nbsp;{\textmu}m). Validation dataset showed that TT can detect significant and true ONL thinning (p = 0.006), more sensitive than manual measurement capabilities (p = 0.069). ThicknessTool can measure retina nuclear layers thickness in a fast, accurate, and precise manner with multi-platform capabilities. In addition, the TT can be customized to user preferences and is freely available to download.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-75501-y},
	author = {Maidana, Daniel E and Notomi, Shoji and Ueta, Takashi and Zhou, Tianna and Joseph, Danica and Kosmidou, Cassandra and Caminal-Mitjana, Josep Maria and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1615225,
	title = {Local photoreceptor cell death differences in the murine model of retinal detachment},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Sep 22},
	pages = {18798},
	abstract = {To investigate local cell death differences in the attached and detached retina at different regions in a murine experimental retinal detachment model. Subretinal injection of sodium hyaluronate was performed in eight-week-old C57BL/6J mice. Retinal regions of interest were defined in relation to their distance from the peak of the retinal detachment, as follows: (1) attached central; (2) attached paracentral; (3) detached apex; and (4) detached base. At day 0, the outer nuclear layer cell count for the attached central, attached paracentral, detached apex, and detached base was 1247.60 {\textpm} 64.62, 1157.80 {\textpm} 163.33, 1264.00 {\textpm} 150.7, and 1013.80 {\textpm} 67.16 cells, respectively. There were significant differences between the detached base vs. attached central, and between detached base vs. detached apex at day 0. The detached apex region displayed a significant and progressive cell count reduction from day 0 to 14. In contrast, the detached base region did not show progressive retinal degeneration in this model. Moreover, only the detached apex region had a significant and progressive cell death rate compared to baseline. Immediate confounding changes with dramatic differences in cell death rates are present across regions of the detached retina. We speculate that mechanical and regional differences in the bullous detached retina can modify the rate of cell death in this model.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-97947-4},
	author = {Maidana, Daniel E and Gonzalez-Buendia, Lucia and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1688351,
	title = {RIPK necrotic cell death pathway in both donor photoreceptor and host immune cells synergize to affect photoreceptor graft survival},
	journal = {FASEB J},
	volume = {37},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {e22847},
	abstract = {Photoreceptor transplant has been put forward as a repair strategy to tackle degenerated retinas. Nonetheless, cell death and immune rejection seriously limit the success of this strategy, with only a small fraction of transplanted cells surviving. Improving the survival of transplanted cells is of critical importance. Recent evidence has identified receptor-interacting protein kinase 3 (RIPK3) as a molecular trigger controlling necroptotic cell death and inflammation. However, its role in photoreceptor transplantation and regenerative medicine has not been studied. We hypothesized that modulation of RIPK3 to address both cell death and immunity could have advantageous effects on photoreceptor survival. In a model of inherited retinal degeneration, deletion of RIPK3 in donor photoreceptor precursors significantly increases the survival of transplanted cells. Simultaneous RIPK3 deletion in donor photoreceptors and recipients maximizes graft survival. Lastly, to discern the role of RIPK3 in the host immune response, bone marrow transplant experiments demonstrated that peripheral immune cell RIPK3 deficiency is protective for both donor and host photoreceptor survival. Interestingly, this finding is independent of photoreceptor transplantation, as the peripheral protective effect is also observed in an additional retinal detachment photoreceptor degeneration model. Altogether, these results indicate that immunomodulatory and neuroprotective strategies targeting the RIPK3 pathway can aid regenerative therapies of photoreceptor transplantation.},
	keywords = {Cell Death, Graft Survival, Humans, Necrosis, Receptor-Interacting Protein Serine-Threonine Kinases, Retina, Retinal Degeneration, Tissue Donors},
	issn = {1530-6860},
	doi = {10.1096/fj.202201137R},
	author = {Maidana, Daniel E and Gonzalez-Buendia, Lucia and Miller, Joan W and Vavvas, Demetrios G}
}
@article {313136,
	title = {Simulated disparity and peripheral blur interact during binocular fusion},
	journal = {J Vis},
	volume = {14},
	number = {8},
	year = {2014},
	month = {2014 Jul 17},
	pages = {13},
	abstract = {We have developed a low-cost, practical gaze-contingent display in which natural images are presented to the observer with dioptric blur and stereoscopic disparity that are dependent on the three-dimensional structure of natural scenes. Our system simulates a distribution of retinal blur and depth similar to that experienced in real-world viewing conditions by emmetropic observers. We implemented the system using light-field photographs taken with a plenoptic camera which supports digital refocusing anywhere in the images. We coupled this capability with an eye-tracking system and stereoscopic rendering. With this display, we examine how the time course of binocular fusion depends on depth cues from blur and stereoscopic disparity in naturalistic images. Our results show that disparity and peripheral blur interact to modify eye-movement behavior and facilitate binocular fusion, and the greatest benefit was gained by observers who struggled most to achieve fusion. Even though plenoptic images do not replicate an individual{\textquoteright}s aberrations, the results demonstrate that a naturalistic distribution of depth-dependent blur may improve 3-D virtual reality, and that interruptions of this pattern (e.g., with intraocular lenses) which flatten the distribution of retinal blur may adversely affect binocular fusion.},
	keywords = {Adult, Eye Movements, Humans, Light, Vision Disorders, Vision Disparity, Vision, Binocular, Young Adult},
	issn = {1534-7362},
	doi = {10.1167/14.8.13},
	author = {Maiello, Guido and Chessa, Manuela and Solari, Fabio and Bex, Peter J}
}
@article {1364512,
	title = {Automated Retinal Imaging System (ARIS) compared with ETDRS protocol color stereoscopic retinal photography to assess level of diabetic retinopathy},
	journal = {Diabetes Technol Ther},
	volume = {14},
	number = {6},
	year = {2012},
	month = {2012 Jun},
	pages = {515-22},
	abstract = {BACKGROUND: Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard-field color stereoscopic retinal photography (ETDRS photos) has been a gold standard for determining diabetic retinopathy (DR) severity. The Automated Retinal Imaging System (ARIS{\texttrademark}, model 110, Visual Pathways, Inc., Prescott, AZ) acquires seven-sequential color stereoscopic digital images (ARIS images) by a semiautomated technician-run process generally corresponding to ETDRS photos. We assessed the correlation between a single semiautomated ARIS imaging session without any re-imaging and ETDRS photos performed by a certified photographer for the determination of DR severity. METHODS: Two independent masked readers graded mydriatic ARIS images and ETDRS photos. A third masked retinal specialist adjudicated discrepancies. Correlation between the two modalities was compared using weighted-κ statistics. RESULTS: We evaluated 211 eyes of 106 patients with varying levels of DR. Partially ungradable images were present in 3.4\% of ETDRS photos versus 31.8\% of ARIS images. Exact agreement and agreement within one level between ETDRS photos and ARIS images using only completely gradable image sets occurred in 69\% (κ=0.81) and 90\% of cases, respectively. Exact agreement for clinically significant macular edema was 92.1\% (κ=0.59). There was 100\% agreement for eyes with high-risk proliferative DR. Within one level of DR severity, 100\% agreement occurred for the following: questionable nonproliferative DR (NPDR), moderate NPDR, and severe NPDR. CONCLUSIONS: Results suggest that semiautomated ARIS images compare favorably with ETDRS photos when full image sets can be obtained; however, partially ungradable image sets occurred almost 10 times more frequently with ARIS images than with ETDRS photos. In the two-thirds of cases where ARIS images can be utilized, ARIS can obtain retinal images comparable to ETDRS photos while requiring less highly trained personnel than generally needed for standard ETDRS photos.},
	keywords = {Adult, Aged, Depth Perception, Diabetic Retinopathy, Diagnostic Techniques, Ophthalmological, Female, Humans, Male, Middle Aged, Observer Variation, Photography, Reproducibility of Results, Retina, Sensitivity and Specificity, Severity of Illness Index, Signal Processing, Computer-Assisted},
	issn = {1557-8593},
	doi = {10.1089/dia.2011.0270},
	author = {Maker, Manvi P and Noble, Jason and Silva, Paolo S and Cavallerano, Jerry D and Murtha, Timothy J and Sun, Jennifer K and Aiello, Lloyd M and Bursell, Sven-Erik and Aiello, Lloyd Paul}
}
@article {1661614,
	title = {Effect of time to operative repair within twenty-four hours on visual acuity outcomes for open globe injuries},
	journal = {Eye (Lond)},
	volume = {37},
	number = {11},
	year = {2023},
	month = {2023 Aug},
	pages = {2351-2355},
	abstract = {PURPOSE: Convention is to perform open globe injury (OGI) repair within 24 h to minimize risk of endophthalmitis. However, there are limited data assessing how time to operative repair (OR) within 24 h impacts postoperative visual acuity (VA). METHODS: Manual retrospective chart review of 633 eyes at Massachusetts Eye and Ear (MEE) with a diagnosis of OGI between 2012 and 2022. Inclusion criteria were primary repair <= 24 h after injury and >=1 month\&nbsp;follow-up. Multivariate regression analysis was conducted with postoperative VA as primary outcome. RESULTS: Of the subjects, 489 (77.3\%) were male and 496 (78.4\%) were white. Demographics of OGI wounds included 320 (50.6\%) rupture and 313 (49.4\%) laceration; 126 (19.9\%) with rAPD, 189 (29.9\%) zone 3 injuries, 449 (71.2\%) uveal prolapse, and 110 (17.4\%) intraocular foreign body. Final postoperative LogMAR VAs consisted of 31\% with a VA \&lt; 1.7, 9\% with a VA of 1.9, 18\% with a VA of 2.3, 27\% with a VA of 2.7, and 11\% with a VA of 3.0. Multivariate analysis showed no significant correlation between time to OR and postoperative VA (p = 0.800) [95\%CI: -0.01,0.01]. Older age (p \&lt; 0.001) [95\%CI: 0.00,0.01], worse presenting VA (p \&lt; 0.001) [95\%CI: 0.17,0.32], rAPD (p \&lt; 0.001) [95\%CI: 0.65,1.0], mechanism of rupture (p \&lt; 0.001) [95\%CI: 0.19,0.54], higher zone of injury (p \&lt; 0.001) [95\%CI: 0.25,0.45], and uveal prolapse (p = 0.003) [95\%CI: 0.09,0.42] were significantly associated with worse final VA. CONCLUSIONS: Time to repair of OGIs within 24 h does not influence final VA. Optimization of surgical and patient factors may contribute more significantly to final VA than prioritizing more rapid time to OR.},
	keywords = {Eye, Eye Injuries, Penetrating, Female, Humans, Male, Prognosis, Random Amplified Polymorphic DNA Technique, Retrospective Studies, Visual Acuity},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-02350-6},
	author = {Makhoul, Kevin G and Bitar, Racquel A and Armstrong, Grayson W and Weinert, Marguerite C and Ivanov, Alexander and Kahale, Francesca and Ta, Thong and Lorch, Alice C}
}
@article {1364513,
	title = {Easy does it when bleaching isolated mouse rods},
	journal = {J Physiol},
	volume = {590},
	number = {11},
	year = {2012},
	month = {2012 Jun 01},
	pages = {2551-2},
	keywords = {Adaptation, Ocular, Animals, Light, Mice, Retinal Rod Photoreceptor Cells},
	issn = {1469-7793},
	doi = {10.1113/jphysiol.2012.233643},
	author = {Makino, Clint L}
}
@article {1424809,
	title = {Modes of Accessing Bicarbonate for the Regulation of Membrane Guanylate Cyclase (ROS-GC) in Retinal Rods and Cones},
	journal = {eNeuro},
	volume = {6},
	number = {1},
	year = {2019},
	month = {2019 Jan-Feb},
	abstract = {The membrane guanylate cyclase, ROS-GC, that synthesizes cyclic GMP for use as a second messenger for visual transduction in retinal rods and cones, is stimulated by bicarbonate. Bicarbonate acts directly on ROS-GC1, because it enhanced the enzymatic activity of a purified, recombinant fragment of bovine ROS-GC1 consisting solely of the core catalytic domain. Moreover, recombinant ROS-GC1 proved to be a true sensor of bicarbonate, rather than a sensor for CO. Access to bicarbonate differed in rods and cones of larval salamander, , of unknown sex. In rods, bicarbonate entered at the synapse and diffused to the outer segment, where it was removed by Cl-dependent exchange. In contrast, cones generated bicarbonate internally from endogenous CO or from exogenous CO that was present in extracellular solutions of bicarbonate. Bicarbonate production from both sources of CO was blocked by the carbonic anhydrase inhibitor, acetazolamide. Carbonic anhydrase II expression was verified immunohistochemically in cones but not in rods. In addition, cones acquired bicarbonate at their outer segments as well as at their inner segments. The multiple pathways for access in cones may support greater uptake of bicarbonate than in rods and buffer changes in its intracellular concentration.},
	issn = {2373-2822},
	doi = {10.1523/ENEURO.0393-18.2019},
	author = {Makino, Clint L and Duda, Teresa and Pertzev, Alexandre and Isayama, Tomoki and Geva, Polina and Sandberg, Michael A and Sharma, Rameshwar K}
}
@article {1364514,
	title = {Enzymatic relay mechanism stimulates cyclic GMP synthesis in rod photoresponse: biochemical and physiological study in guanylyl cyclase activating protein 1 knockout mice},
	journal = {PLoS One},
	volume = {7},
	number = {10},
	year = {2012},
	month = {2012},
	pages = {e47637},
	abstract = {Regulation of cGMP synthesis by retinal membrane guanylyl cyclase isozymes (RetGC1 and RetGC2) in rod and cone photoreceptors by calcium-sensitive guanylyl cyclase activating proteins (GCAP1 and GCAP2) is one of the key molecular mechanisms affecting the response to light and is involved in congenital retinal diseases. The objective of this study was to identify the physiological sequence of events underlying RetGC activation in vivo, by studying the electrophysiological and biochemical properties of mouse rods in a new genetic model lacking GCAP1. The GCAP1(-/-) retinas expressed normal levels of RetGC isozymes and other phototransduction proteins, with the exception of GCAP2, whose expression was elevated in a compensatory fashion. RetGC activity in GCAP1(-/-) retinas became more sensitive to Ca(2+) and slightly increased. The bright flash response in electroretinogram (ERG) recordings recovered quickly in GCAP1(-/-), as well as in RetGC1(-/-)GCAP1(-/-), and RetGC2(-/-)GCAP1(-/-) hybrid rods, indicating that GCAP2 activates both RetGC isozymes in vivo. Individual GCAP1(-/-) rod responses varied in size and shape, likely reflecting variable endogenous GCAP2 levels between different cells, but single-photon response (SPR) amplitude and time-to-peak were typically increased, while recovery kinetics remained faster than in wild type. Recovery from bright flashes in GCAP1(-/-) was prominently biphasic, because rare, aberrant SPRs producing the slower tail component were magnified. These data provide strong physiological evidence that rod photoresponse recovery is shaped by the sequential recruitment of RetGC isozyme activation by GCAPs according to the different GCAP sensitivities for Ca(2+) and specificities toward RetGC isozymes. GCAP1 is the {\textquoteright}first-response{\textquoteright} sensor protein that stimulates RetGC1 early in the response and thus limits the SPR amplitude, followed by activation of GCAP2 that adds stimulation of both RetGC1 and RetGC2 to speed-up photoreceptor recovery.},
	keywords = {Animals, Calcium, Cyclic GMP, Electroretinography, Feedback, Physiological, Gene Targeting, Guanylate Cyclase, Guanylate Cyclase-Activating Proteins, Isoenzymes, Light, Mice, Mice, Knockout, Models, Biological, Retinal Rod Photoreceptor Cells},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0047637},
	author = {Makino, Clint L and Wen, Xiao-Hong and Olshevskaya, Elena V and Peshenko, Igor V and Savchenko, Andrey B and Dizhoor, Alexander M}
}
@article {1364515,
	title = {Rhodopsin expression level affects rod outer segment morphology and photoresponse kinetics},
	journal = {PLoS One},
	volume = {7},
	number = {5},
	year = {2012},
	month = {2012},
	pages = {e37832},
	abstract = {BACKGROUND: The retinal rod outer segment is a sensory cilium that is specialized for the conversion of light into an electrical signal. Within the cilium, up to several thousand membranous disks contain as many as a billion copies of rhodopsin for efficient photon capture. Disks are continually turned over, requiring the daily synthesis of a prodigious amount of rhodopsin. To promote axial diffusion in the aqueous cytoplasm, the disks have one or more incisures. Across vertebrates, the range of disk diameters spans an order of magnitude, and the number and length of the incisures vary considerably, but the mechanisms controlling disk architecture are not well understood. The finding that transgenic mice overexpressing rhodopsin have enlarged disks lacking an incisure prompted us to test whether lowered rhodopsin levels constrain disk assembly. METHODOLOGY/PRINCIPAL FINDINGS: The structure and function of rods from hemizygous rhodopsin knockout (R+/-) mice with decreased rhodopsin expression were analyzed by transmission electron microscopy and single cell recording. R+/- rods were structurally altered in three ways: disk shape changed from circular to elliptical, disk surface area decreased, and the single incisure lengthened to divide the disk into two sections. Photocurrent responses to flashes recovered more rapidly than normal. A spatially resolved model of phototransduction indicated that changes in the packing densities of rhodopsin and other transduction proteins were responsible. The decrease in aqueous outer segment volume and the lengthened incisure had only minor effects on photon response amplitude and kinetics. CONCLUSIONS/SIGNIFICANCE: Rhodopsin availability limits disk assembly and outer segment girth in normal rods. The incisure may buffer the supply of structural proteins needed to form larger disks. Decreased rhodopsin level accelerated photoresponse kinetics by increasing the rates of molecular collisions on the membrane. Faster responses, together with fewer rhodopsins, combine to lower overall sensitivity of R+/- rods to light.},
	keywords = {Animals, Kinetics, Mice, Retinal Rod Photoreceptor Cells, Rhodopsin, Rod Cell Outer Segment, Vision, Ocular},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0037832},
	author = {Makino, Clint L and Wen, Xiao-Hong and Michaud, Norman A and Covington, Henry I and DiBenedetto, Emmanuele and Hamm, Heidi E and Lem, Janis and Caruso, Giovanni}
}
@article {1598039,
	title = {The conjunctival extracellular matrix, related disorders and development of substrates for conjunctival restoration},
	journal = {Ocul Surf},
	year = {2021},
	month = {2021 Jun 05},
	abstract = {The conjunctiva can be damaged by numerous diseases with scarring, loss of tissue and dysfunction. Depending on extent of damage, restoration of function may require a conjunctival graft. A wide variety of biological and synthetic substrates have been tested in the search for optimal conditions for ex vivo culture of conjunctival epithelial cells as a route toward tissue grafts. Each substrate has specific advantages but also disadvantages related to their unique physical and biological characteristics, and identification and development of an improved substrate remains a priority. To achieve the goal of mimicking and restoring a biological material, requires information from the material. Specifically, extracellular matrix (ECM) derived from conjunctival tissue. Knowledge of the composition and structure of native ECM and identifying contributions of individual components to its function would enable using or mimicking those components to develop improved biological substrates. ECM is comprised of two components: basement membrane secreted predominantly by epithelial cells containing laminins and type IV collagens, which directly support epithelial and goblet cell adhesion differentiation and growth and, interstitial matrix secreted by fibroblasts in lamina propria, which provides mechanical and structural support. This review presents current knowledge on anatomy, composition of conjunctival ECM and related conjunctival disorders. Requirements of potential substrates for conjunctival tissue engineering and transplantation are discussed. Biological and synthetic substrates and their components are described in an accompanying review.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.05.011},
	author = {Makuloluwa, Aruni K and Hamill, Kevin J and Rauz, Saaeha and Bosworth, Lucy and Haneef, Atikah and Romano, Vito and Williams, Rachel L and Dartt, Darlene A. and Kaye, Stephen B}
}
@article {1598040,
	title = {Biological tissues and components, and synthetic substrates for conjunctival cell transplantation},
	journal = {Ocul Surf},
	year = {2021},
	month = {2021 Jun 10},
	abstract = {The conjunctiva is the largest component of the ocular surface. It can be damaged by various pathological processes leading to scarring, loss of tissue and dysfunction. Depending on the amount of damage, restoration of function may require a conjunctival graft. Numerous studies have investigated biological and synthetic substrates in the search for optimal conditions for the ex vivo culture of conjunctival epithelial cells that can be used as tissue grafts for transplantation. These substrates have advantages and disadvantages that are specific to the characteristics of each material; the development of an improved material remains a priority. This review is the second of a two-part review in The Ocular Surface. In the first review, the structure and function of the conjunctiva was evaluated with a focus on the extracellular matrix and the basement membrane, and biological and mechanical characteristics of the ideal substrate with recommendations for further studies. In this review the types of biological and synthetic substrates used for conjunctival transplantation are discussed including substrates based on the extracellular matrix. .},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.06.003},
	author = {Makuloluwa, Aruni K and Hamill, Kevin J and Rauz, Saaeha and Bosworth, Lucy and Haneef, Atikah and Romano, Vito and Williams, Rachel L and Dartt, Darlene A. and Kaye, Stephen B}
}
@article {1632302,
	title = {Authors{\textquoteright} response},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {3},
	year = {2022},
	month = {2022 May-Jun},
	pages = {880-882},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2022.01.012},
	author = {Maleki, Arash and Colombo, Amanda and Manhapra, Ambika and Foster, C Stephen}
}
@article {1573099,
	title = {Ictal and interictal brain activation in episodic migraine: Neural basis for extent of allodynia},
	journal = {PLoS One},
	volume = {16},
	number = {1},
	year = {2021},
	month = {2021},
	pages = {e0244320},
	abstract = {In some patients, migraine attacks are associated with symptoms of allodynia which can be localized (cephalic) or generalized (extracephalic). Using functional neuroimaging and cutaneous thermal stimulation, we aimed to investigate the differences in brain activation of patients with episodic migraine (n = 19) based on their allodynic status defined by changes between ictal and interictal pain tolerance threshold for each subject at the time of imaging. In this prospective imaging study, differences were found in brain activity between the ictal and interictal visits in the brainstem/pons, thalamus, insula, cerebellum and cingulate cortex. Significant differences were also observed in the pattern of activation along the trigeminal pathway to noxious heat stimuli in no allodynia vs. generalized allodynia in the thalamus and the trigeminal nucleus but there were no activation differences in the trigeminal ganglion. The functional magnetic resonance imaging (fMRI) findings provide direct evidence for the view that in migraine patients who are allodynic during the ictal phase of their attacks, the spinal trigeminal nucleus and posterior thalamus become hyper-responsive (sensitized)-to the extent that they mediate cephalic and extracephalic allodynia, respectively. In addition, descending analgesic systems seem as "switched off" in generalized allodynia.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0244320},
	author = {Maleki, Nasim and Szabo, Edina and Becerra, Lino and Moulton, Eric and Scrivani, Steven J and Burstein, Rami and Borsook, David}
}
@article {913501,
	title = {Selective Laser Trabeculoplasty in Controlled Uveitis with Steroid-Induced Glaucoma.},
	journal = {Ophthalmology},
	volume = {123},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {2630-2632},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.07.027},
	author = {Maleki, Arash and Swan, Robert T and Lasave, Andres F and Ma, Lina and Foster, C Stephen}
}
@article {1598035,
	title = {Pediatric uveitis: A comprehensive review},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {2},
	year = {2022},
	month = {2022 Mar-Apr},
	pages = {510-529},
	abstract = {Pediatric uveitis accounts for 5-10\% of all uveitis. Uveitis in children differs from adult uveitis in that it is commonly asymptomatic and can become chronic and cause damage to ocular structures. The diagnosis might be delayed for multiple reasons, including the preverbal age and difficulties in examining young children. Pediatric uveitis may be infectious or noninfectious in etiology. The etiology of noninfectious uveitis is presumed to be autoimmune or autoinflammatory. The most common causes of uveitis in this age group are idiopathic and juvenile idiopathic arthritis-associated uveitis. The stepladder approach for the treatment of pediatric uveitis is based on expert opinion and algorithms proposed by multidisciplinary panels. Uveitis morbidities in pediatric patients include cataract, glaucoma, and amblyopia. Pediatric patients with uveitis should be frequently examined until remission is achieved. Once in remission, the interval between follow-up visits can be extended; however, it is recommended that even after remission the child should be seen every 8-12 weeks depending on the history of uveitis and the medications used. Close follow up is also necessary as uveitis can flare up during immunomodulatory therapy. It is crucial to measure the impact of uveitis, its treatment, and its complications on the child and the child{\textquoteright}s family. Visual acuity can be considered as an acceptable criterion for assessing visual function. Additionally, the number of cells in the anterior chamber can be a measure of disease activity. We review different aspects of pediatric uveitis. We discuss the mechanisms of noninfectious uveitis, including autoimmune and autoinflammatory etiologies, and the risks of developing uveitis in children with systemic rheumatologic diseases. We address the risk factors for developing morbidities, the Standardization of Uveitis Nomenclature (SUN) criteria for timing and anatomical classifications, and describe a stepladder approach in the treatment of pediatric uveitis based on expert opinion and algorithms proposed by multi-disciplinary panels. In this review article, We describe the most common entities for each type of anatomical classification and complications of uveitis for the pediatric population. Additionally, we address monitoring of children with uveitis and evaluation of Quality of Life.},
	keywords = {Adult, Cataract, Child, Child, Preschool, Humans, Quality of Life, Retrospective Studies, Uveitis, Visual Acuity},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2021.06.006},
	author = {Maleki, Arash and Anesi, Stephen D and Look-Why, Sydney and Manhapra, Ambika and Foster, C Stephen}
}
@article {1528424,
	title = {Fixed-Luminance and Multi-Luminance Flicker Electroretinography Parameters in Patients with Early Active Birdshot Chorioretinopathy},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Aug 20},
	pages = {1-7},
	abstract = {Purpose To evaluate the parameters of the Fixed-Luminance and Multi-Luminance flicker electroretinography protocol among patients with early active birdshot chorioretinopathy. Methods Fixed-Luminance magnitude, Fixed-Luminance phase, Multi-Luminance magnitude area under the curve, and Multi-Luminance phase area under the curve parameters were compared between early active birdshot chorioretinopathy patients and an age-matched control group. Results There was no statistically significant difference between the Fixed-Luminance flicker magnitude ( =\&nbsp;.6), the Fixed-Luminance flicker phase ( =\&nbsp;.9), and the Multi-Luminance flicker phase area under the curve ( =\&nbsp;.55) when each was compared to the normal population; however, the difference between the mean Multi-Luminance flicker magnitude area under the curve in our patients and the healthy control group was statistically significant. ( =\&nbsp;.003) Conclusions Multi-Luminance flicker magnitude area under the curve has been shown to be significantly different from the normal population in the early active course of the disease. Abbreviations BSCR: birdshot chorioretinopathy; cd: Cadmium; ERG: Electroretinography; FA: Fluorescein angiography; FL-: Fixed-luminance; HVF: Humphrey visual field; Hz: Hertz; ICG: Indocyanine green; m: Square meter; ML-: Multi-luminance; ms: millisecond; SITA: Swedish interactive thresholding algorithm; SWAP: Short wave-length automated perimetry.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1797113},
	author = {Maleki, Arash and Ueberroth, Jordan A and Manhapra, Ambika and Walsh, Marisa and Asgari, Soheila and Chang, Peter Y and Anesi, Stephen D and Foster, C Stephen}
}
@article {603911,
	title = {Short-Wavelength Automated Perimetry Parameters at Baseline and Following Remission in Patients With Birdshot Retinochoroidopathy.},
	journal = {Am J Ophthalmol},
	volume = {163},
	year = {2016},
	month = {2016 Mar},
	pages = {83-92.e6},
	abstract = {PURPOSE: To identify changes in short-wavelength automated perimetry patterns and parameters between the active and inactive states. DESIGN: Retrospective cohort study with age-matched, normal controls. METHODS: setting: Private tertiary referral center. STUDY POPULATION: Seventy-five eyes of 38 patients with active birdshot retinochoroidopathy and 37 eyes of 37 historical normal controls. INTERVENTION: Thirty-seven patients received immunomodulatory therapy. A fluocinolone acetonide intravitreal implant (Retisert) was implanted in both eyes of 1 patient as an initial treatment. MAIN OUTCOME MEASURES: Changes in short-wavelength automated perimetry total deviation scores, pattern deviation scores, mean deviation, and pattern standard deviation in the active phase and the remission state. RESULTS: Mean deviation (P\&nbsp;= .006), pattern standard deviation (P\&nbsp;= .001), total deviation score (P\&nbsp;= .002), and pattern deviation score (P\&nbsp;= .007) were significantly different from the active phase to the remission state. The length of time required to achieve remission did not significantly affect the changes in mean deviation (regression coefficient\&nbsp;= 0.01; P\&nbsp;= .92), pattern standard deviation (regression coefficient\&nbsp;= 0.01; P\&nbsp;= .87), total deviation score (regression coefficient\&nbsp;=\&nbsp;-0.1; P\&nbsp;= .32), or pattern deviation score (regression coefficient\&nbsp;= 0.1; P\&nbsp;= .36) from the active phase to the remission state. CONCLUSION: There was significant improvement in total deviation score, pattern deviation score, mean deviation, and pattern standard deviation on short-wavelength automated perimetry as patients achieved remission. Short-wavelength automated perimetry appears to be a useful and complementary modality\&nbsp;in monitoring disease activity in birdshot retinochoroidopathy.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.11.024},
	author = {Maleki, Arash and Swan, Robert T and Silpa-Archa, Sukhum and Preble, Janine M and He, Yuchen and Foster, C Stephen}
}
@article {1658668,
	title = {Adalimumab Monotherapy in the Treatment of Idiopathic Multifocal Choroiditis: A Case Report},
	journal = {Case Rep Ophthalmol},
	volume = {13},
	number = {3},
	year = {2022},
	month = {2022 Sep-Dec},
	pages = {793},
	abstract = {In this study, we report a case of multifocal choroiditis that was successfully treated with adalimumab monotherapy. A 25-year-old male presented with a history of bilateral multifocal choroiditis which was resistant to a combination of azathioprine, valacyclovir, and prednisone. Dilated fundoscopy revealed small creamy-yellow lesions around the arcades in both eyes (OU). Indocyanine green angiography (ICGA) revealed active hypocyanescent lesions around the arcades and macula OU. Valacyclovir was stopped, adalimumab subcutaneous injections biweekly were added to the regimen, and prednisone was tapered after the second adalimumab loading dose. At 3-month follow-up, ocular examination and ICGA were unremarkable OU. After 30 months of remission, azathioprine was tapered and stopped. After 40 months of remission, adalimumab was tapered and stopped. Four months after stopping adalimumab injections, the patient returned with new floaters in his right eye (OD). ICGA and macular optical coherence tomography detected active lesions OU. The patient was restarted on adalimumab subcutaneous injections as monotherapy. At 3-month follow-up visit, his symptoms had resolved, and ICGA showed resolution of the lesions OD and improvement of the lesions in the left eye (OS). He has been in remission for 6 months at the time of writing since restarting adalimumab monotherapy. We conclude from this study that long-term adalimumab monotherapy can be employed effectively and safely in the re-treatment of patients with multifocal choroiditis resistant to other immunomodulatory therapy even after successful tapering and discontinuation of concurrent therapies.},
	issn = {1663-2699},
	doi = {10.1159/000525504},
	author = {Maleki, Arash and Philip, Andrew and Foster, C Stephen}
}
@article {1511501,
	title = {Combination of Intravenous Methotrexate and Methylprednisolone Therapy in the Treatment of Severe Ocular Inflammatory Diseases},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 May 14},
	pages = {1-5},
	abstract = {: To evaluate the efficacy of intravenous methotrexate and methylprednisolone in severe, sight-threatening ocular inflammatory conditions.: This was a retrospective observational case series. Patients who had received intravenous methotrexate for ocular inflammation with at least 24\&nbsp;months of follow-up were included in the study.: Ten patients (20 eyes) were included in this study. Mean age of the patients was 47.2\&nbsp;{\textpm}\&nbsp;17.7 (range:19-74). At 1-month follow-up visit, nine patients showed improvement and one patient failed treatment. At 12-month follow-up visit, all patients were in remission. Two patients were only on intravenous methotrexate infusions. At twenty-four-month follow-up visit, only one patient, in remission, was on intravenous methotrexate therapy. Leukopenia was the only adverse effect observed.: Intravenous methotrexate and methylprednisolone infusions can be an effective method of treatment in patients with severe, sight-threatening ocular inflammatory conditions.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1746356},
	author = {Maleki, Arash and Ueberroth, Jordan A and Walsh, Marisa and Foster, Frances and Chang, Peter Y and Anesi, Stephen D and Foster, Charles Stephen}
}
@article {1532353,
	title = {Diagnostic and Prognostic Roles of Serum Interleukin-6 Levels in Patients with Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Sep 23},
	pages = {1-6},
	abstract = {PURPOSE: To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis. METHODS: This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels. RESULTS: Mean IL-6 level was 1.77\&nbsp;{\textpm}\&nbsp;0.97\&nbsp;pg/ml and 10.2\&nbsp;{\textpm}\&nbsp;9.7\&nbsp;pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant ( =\&nbsp;.015, =\&nbsp;.000, =\&nbsp;.03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR\&nbsp;=\&nbsp;10.83, \&lt;\&nbsp;.001), Age (OR\&nbsp;=\&nbsp;0.95, =\&nbsp;.03) and number of flare-ups (OR\&nbsp;=\&nbsp;2.9, =\&nbsp;.02). CONCLUSION: Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1815799},
	author = {Maleki, Arash and Gomez, Sebastian and Asgari, Soheila and Bosenberg, Zoe and Manhapra, Ambika and Walsh, Marisa and Weng, Angelina and Tseng, Catherine and He, Celestine and Anesi, Stephen Damien and Foster, C Stephen}
}
@article {1586178,
	title = {Response to the Second TNF-α Inhibitor (Adalimumab or Infliximab) after Failing the First One in Refractory Idiopathic Inflammatory Retinal Vascular Leakage},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Mar 01},
	pages = {1-10},
	abstract = {: To determine the response to the second TNF-α inhibitor (adalimumab and infliximab) after failing the first agent in idiopathic inflammatory retinal vascular leakage.: This was a retrospective observational case series. Patients with the diagnosis of idiopathic inflammatory retinal vascular leakage who had received both infliximab and adalimumab were included in the study.: Twelve and 15 patients received adalimumab (Group one) and infliximab (Group two) as the first treatment, respectively. The remission rates between Group one (58.3\%) and Group two (66.7\%) were not statistically significant. ( =\&nbsp;.4) As the second agent, adalimumab was more effective in younger patients (27.5\&nbsp;{\textpm}\&nbsp;20.6) compared to older patients (48.75\&nbsp;{\textpm}\&nbsp;10.2). ( =\&nbsp;.03). Moreover, patients with lower vision responded marginally better to infliximab as the second treatment ( =\&nbsp;.06).: Either TNF-α inhibitor, adalimumab and infliximab, can be employed in the treatment of the patients with idiopathic inflammatory retinal vascular leakage who fail one of these agents.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1869787},
	author = {Maleki, Arash and Garcia, Cristina M and Asgari, Soheila and Manhapra, Ambika and Foster, Charles Stephen}
}
@article {680421,
	title = {Progress in the understanding and utilization of biologic response modifiers in the treatment of uveitis.},
	journal = {Expert Rev Clin Immunol},
	volume = {12},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {775-86},
	abstract = {Uveitis is the third most common cause of blindness in developed countries. Considering the systemic and local complications of long-term corticosteroid therapy and the intolerance due to side effects and ineffectiveness of conventional chemotherapy, use of biologic response modifiers is a reasonable alternative in the treatment of non-infectious uveitis and persistent uveitic macular edema. The majority of the evidence presented here comes from open uncontrolled analyses. Based on these studies, tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, have been shown to be effective in the treatment of non-infectious uveitis in numerous studies. More research is necessary, particularly multi-center randomized clinical trials, to address the choice of biologic response modifier agent and the length of treatment as we employ biologic response modifiers in different types of uveitis and persistent uveitic macular edema.},
	issn = {1744-8409},
	doi = {10.1586/1744666X.2016.1166052},
	author = {Maleki, Arash and Meese, Halea and Sahawneh, Haitham and Foster, C Stephen}
}
@article {1603841,
	title = {Acquired Vitelliform-Like Lesion in Uveitis: A case-series},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Jul 27},
	pages = {1-10},
	abstract = {PURPOSE: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis. PATIENTS AND METHODS: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL. RESULTS: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage (p =\&nbsp;.005), the presence of vasculitis (p =\&nbsp;.01), the presence of active choroiditis (p =\&nbsp;.01), and the presence of CME on OCT (p =\&nbsp;.008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation (p \&lt;\&nbsp;.001) and the last follow-up visit (p =\&nbsp;.014) in the AVLL group. CONCLUSION: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2021.1954201},
	author = {Maleki, Arash and Look-Why, Sydney and Asgari, Soheila and Manhapra, Ambika and Gomez, Sebastian and Foster, C Stephen}
}
@article {1137891,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {124},
	number = {8},
	year = {2017},
	month = {2017 Aug},
	pages = {e64-e65},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.03.029},
	author = {Maleki, Arash and Swan, Robert T and Lasave, Andres F and Ma, Lina and Foster, C Stephen}
}
@article {1653600,
	title = {Acute macular neuroretinopathy in a patient with birdshot chorioretinopathy after intravitreal triamcinolone suspension injection},
	journal = {Eur J Ophthalmol},
	volume = {33},
	number = {5},
	year = {2023},
	month = {2023 Sep},
	pages = {NP35-NP40},
	abstract = {PURPOSE: To report a case of acute macular neuroretinopathy (AMN) after intravitreal triamcinolone acetonide (TRIESENCE{\textregistered}) injection for cystoid macular edema secondary to birdshot chorioretinopathy. METHOD: A case report. PATIENT: A 62-year-old female. RESULTS: The patient presented with acutely decreased vision and a ring scotoma around her central vision three days after intravitreal triamcinolone acetonide (TRIESENCE{\textregistered}) injection for cystoid macular edema in her right eye (OD) secondary to birdshot chorioretinopathy. She had undergone pars plana vitrectomy, cataract extraction, and secondary intraocular lens implantation OD three months prior to the recent injection. Best-corrected visual acuity (BCVA) was 20/1000 OD and 20/50 OS. Intraocular pressure was 21 mmHg OD and 12 mmHg OS. Fluorescein angiography demonstrated a hypofluorescent area in the perifoveal zone OD. Optical coherence tomography OD depicted hyperreflective areas in the outer nuclear layer, outer plexiform layer, and retinal pigment epithelium. We diagnosed her with AMN OD and started her on brimonidine three times a day OD. She came back a week later with resolved scotoma and her vision improved to 20/60 OD. Five weeks later, BCVA was 20/40 and Intraocular pressures (IOP) was 12 mmHg OD. CONCLUSIONS AND IMPORTANCE: Intravitreal triamcinolone injection may be a cause of AMN with cystoid macular edema (CME) and borderline-high intraocular pressure. Brimonidine may be an effective treatment for these patients in the early course of the disease.},
	keywords = {Birdshot Chorioretinopathy, Female, Glucocorticoids, Humans, Intravitreal Injections, Macular Edema, Middle Aged, Tomography, Optical Coherence, Treatment Outcome, Triamcinolone Acetonide, Vitreous Body, White Dot Syndromes},
	issn = {1724-6016},
	doi = {10.1177/11206721221124653},
	author = {Maleki, Arash and Fernandez, Carla C and Philip, Andrew M and Manhapra, Ambika and Chang, Peter Y and Foster, C Stephen}
}
@article {1732541,
	title = {Juvenile idiopathic arthritis and its associated uveitis},
	journal = {Expert Rev Clin Immunol},
	year = {2023},
	month = {2023 Jul 04},
	pages = {1-13},
	abstract = {INTRODUCTION: Juvenile idiopathic arthritis is the most common chronic rheumatologic disease in children. Uveitis is the most common extra-articular manifestation of JIA, and it can be a sight-threatening condition. AREAS COVERED: In this review article, we discussed epidemiology, risk factors, clinical presentation, supportive laboratory tests, treatment options, and complications of Juvenile idiopathic arthritis and Juvenile idiopathic arthritis associated uveitis. We covered conventional immunomodulatory therapy and biologic response modifiers agents for different types of Juvenile idiopathic arthritis and their associated uveitis. Finally, we discussed the course of disease, functional outcome, and the quality of life of Juvenile idiopathic arthritis and Juvenile idiopathic arthritis-associated uveitis. EXPERT OPINION: Although clinical outcomes of Juvenile idiopathic arthritis and its associated uveitis have been improved over the past three decades by biologic response modifier agents, a significant proportion of patients require active treatment into adult life therefore screening and monitoring of these patients is required during the patient{\textquoteright}s entire life. The limited number of food and drug administration approved biologic response modifier agents for the treatment of Juvenile idiopathic arthritis associated uveitis justify more randomized clinical trials with new medications in this field.},
	issn = {1744-8409},
	doi = {10.1080/1744666X.2023.2231154},
	author = {Maleki, Arash and Patel, Priya D and Foster, C Steven}
}
@article {1062841,
	title = {INFLIXIMAB THERAPY IN PATIENTS WITH NONINFECTIOUS INTERMEDIATE UVEITIS RESISTANT TO CONVENTIONAL IMMUNOMODULATORY THERAPY},
	journal = {Retina},
	volume = {37},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {836-843},
	abstract = {
	PURPOSE: To examine the efficacy and safety of infliximab therapy in the treatment for noninfectious intermediate uveitis resistant to conventional immunomodulatory therapy. METHODS: Forty-four eyes of 23 patients with resistant noninfectious intermediate uveitis who were treated with infliximab infusions for a minimum period of 3 months were included. Demographic data, clinical data, and fluorescein angiography and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution database between August 2005 and February 2014. Clinical response, improvement in ancillary test findings, and major side effects were evaluated. RESULTS: Nineteen patients (82.6\%) achieved remission. The mean duration of treatment to induce remission was 3.99 {\textpm} 3.06 months (range, 2-14.7). Cystoid macular edema was the only complication observed during the course of the treatment in 1 eye (2.27\%). One patient (4.3\%) developed major side effects. None of the patients developed central or peripheral demyelinating neuropathies or multiple sclerosis. At 6 months after remission, logarithm of the minimum angle of resolution visual acuity (P = 0.006) and central macular thickness (P = 0.03) showed significant improvement in patients who achieved remission. CONCLUSION: A significant number of patients achieved remission on infliximab therapy. The incidence of major side effects in our cohort was low.

},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001269},
	author = {Maleki, Arash and Sahawneh, Haitham F and Ma, Lina and Meese, Halea and He, Yuchen and Foster, C Stephen}
}
@article {1593868,
	title = {Clinical course and poor prognostic factors of Vogt-Koyanagi-Harada disease in a tertiary uveitis clinic},
	journal = {Can J Ophthalmol},
	volume = {57},
	number = {2},
	year = {2022},
	month = {2022 Apr},
	pages = {142-144},
	keywords = {Ambulatory Care Facilities, Humans, Prognosis, Uveitis, Uveomeningoencephalitic Syndrome},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2021.04.005},
	author = {Maleki, Arash and Anesi, Stephen D and Look-Why, Sydney and Asgari, Soheila and Manhapra, Ambika and Foster, C Stephen}
}
@article {1635640,
	title = {Birdshot Chorioretinopathy: Resistant versus Responsive},
	journal = {Ocul Immunol Inflamm},
	volume = {31},
	number = {3},
	year = {2023},
	month = {2023 Apr},
	pages = {477-482},
	abstract = {PURPOSE: To search findings that can explain the heterogeneity between Resistant and Responsive patients with birdshot chorioretinopathy. PATIENTS AND METHODS: This was a retrospective observational case series on "Responsive" versus "Resistant" birdshot chorioretinopathy. RESULTS: One-hundred-eighty and Ninety-nine patients were included in the Responsive and Resistant groups respectively. Multivariate analysis of paraclinical variables at the first visit demonstrated that mean deviation (p = .04), pattern standard deviation (p \&lt; .001), optic nerve head leakage (p = .012), large vessel leakage and staining (p = .01), and macular small vessel leakage (p = .03) were statistically significantly different between the two groups; however, at the visit preceding successful therapy, only macular small vessel leakage (p = .01) was statistically significantly different between the two groups. CONCLUSION: .Small vessel leakage in the macular area and/or optic nerve head leakage at the earliest visit might be risk factors for resistant birdshot chorioretinopathy.},
	keywords = {Birdshot Chorioretinopathy, Chorioretinitis, Fluorescein Angiography, Humans, Retrospective Studies, Visual Acuity},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2032193},
	author = {Maleki, Arash and Look-Why, Sydney and Manhapra, Ambika and Asgari, Soheila and Garcia, Cristina M and Al-Dabbagh, Alaa and Tsang, Catherine and Chang, Peter Y and Anesi, Stephen D and Foster, C Stephen}
}
@article {931121,
	title = {VISUAL OUTCOME AND POOR PROGNOSTIC FACTORS IN ISOLATED IDIOPATHIC RETINAL VASCULITIS.},
	journal = {Retina},
	volume = {36},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {1979-85},
	abstract = {PURPOSE: To describe the clinical course, visual outcome, and prognosis of isolated, idiopathic retinal vasculitis. METHODS: Eighty patients (150 eyes) with isolated, idiopathic retinal vasculitis were included. Demographic data, clinical data, complications at the initial visit and during follow-up, fluorescein angiography, and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution (MERSI) database from September 2005 to February 2015. RESULTS: Seventy-five (93.7\%) patients required treatment with immunomodulatory therapy. Of those 75 patients, 60 (75\%) patients were able to achieve durable remission. Factors which were independently significant predictive of poor visual outcome were lower initial visual acuity (OR: 3.78; 95\% CI: 1.75-8.16; P = 0.001), cystoid macular edema (OR: 5.54; 95\% CI: 1.81-16.99; P = 0.003), and macular ischemia (OR: 5.12; 95\% CI: 1.12-23.04; P = 0.036). CONCLUSION: The majority (67.25\%) of our patients enjoyed a good visual outcome (most recent visit best-corrected visual acuity equal to or better than 20/40 and within one line or better from the baseline) with immunomodulatory therapy. We found that cystoid macular edema, macular ischemia, and lower best-corrected visual acuity during the first consultation visit were significant independent risk factors for poor visual outcome.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001019},
	author = {Maleki, Arash and Cao, Jennifer H and Silpa-Archa, Sukhum and Foster, C Stephen}
}
@article {280871,
	title = {Genome-wide identification and characterization of functional neuronal activity-dependent enhancers.},
	journal = {Nat Neurosci},
	volume = {17},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {1330-9},
	abstract = {Experience-dependent gene transcription is required for nervous system development and function. However, the DNA regulatory elements that control this program of gene expression are not well defined. Here we characterize the enhancers that function across the genome to mediate activity-dependent transcription in mouse cortical neurons. We find that the subset of enhancers enriched for monomethylation of histone H3 Lys4 (H3K4me1) and binding of the transcriptional coactivator CREBBP (also called CBP) that shows increased acetylation of histone H3 Lys27 (H3K27ac) after membrane depolarization of cortical neurons functions to regulate activity-dependent transcription. A subset of these enhancers appears to require binding of FOS, which was previously thought to bind primarily to promoters. These findings suggest that FOS functions at enhancers to control activity-dependent gene programs that are critical for nervous system function and provide a resource of functional cis-regulatory elements that may give insight into the genetic variants that contribute to brain development and disease.},
	issn = {1546-1726},
	doi = {10.1038/nn.3808},
	author = {Malik, Athar N and Vierbuchen, Thomas and Hemberg, Martin and Rubin, Alex A and Ling, Emi and Couch, Cameron H and Stroud, Hume and Spiegel, Ivo and Farh, Kyle Kai-How and Harmin, David A and Greenberg, Michael E}
}
@article {1661826,
	title = {Retinopathy During the First 5 Years of Type 1 Diabetes and Subsequent Risk of Advanced Retinopathy},
	journal = {Diabetes Care},
	year = {2022},
	month = {2022 Dec 13},
	abstract = {OBJECTIVE: To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals. RESEARCH DESIGN AND METHODS: Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years. Early-onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes. RESULTS: In unadjusted models, individuals with EDR (n = 484) had an increased subsequent risk of PDR (hazard ratio [HR] 1.51 [95\% CI 1.12, 2.02], P = 0.006), CSME (HR 1.44 [1.10, 1.88], P = 0.008), and diabetes-related retinal photocoagulation (HR 1.48 [1.12, 1.96], P = 0.006) compared with individuals without EDR (n = 369). These associations remained significant when adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and estimated glomerular filtration rate (HR 1.47 [95\% CI 1.04, 2.06], P = 0.028). CONCLUSIONS: These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early-onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.},
	issn = {1935-5548},
	doi = {10.2337/dc22-1711},
	author = {Malone, John I and Gao, Xiaoyu and Lorenzi, Gayle M and Raskin, Philip and White, Neil H and Hainsworth, Dean P and Das, Arup and Tamborlane, William and Wallia, Amisha and Aiello, Lloyd P and Bebu, Ionut and Diabetes Control and Complications Trial (DCCT)-Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group}
}
@article {1698376,
	title = {Object identification in cerebral visual impairment characterized by gaze behavior and image saliency analysis},
	journal = {Brain Dev},
	volume = {45},
	number = {8},
	year = {2023},
	month = {2023 Sep},
	pages = {432-444},
	abstract = {Individuals with cerebral visual impairment (CVI) have difficulties identifying common objects, especially when presented as cartoons or abstract images. In this study, participants were shown a series of images of ten common objects, each from five possible categories ranging from abstract black \&amp; white line drawings to color photographs. Fifty individuals with CVI and 50 neurotypical controls verbally identified each object and success rates and reaction times were collected. Visual gaze behavior was recorded using an eye tracker to quantify the extent of visual search area explored and number of fixations. A receiver operating characteristic (ROC) analysis was also carried out to compare the degree of alignment between the distribution of individual eye gaze patterns and image saliency features computed by the graph-based visual saliency (GBVS) model. Compared to controls, CVI participants showed significantly lower success rates and longer reaction times when identifying objects. In the CVI group, success rate improved moving from abstract black \&amp; white images to color photographs, suggesting that object form (as defined by outlines and contours) and color are important cues for correct identification. Eye tracking data revealed that the CVI group showed significantly greater visual search areas and number of fixations per image, and the distribution of eye gaze patterns in the CVI group was less aligned with the high saliency features of the image compared to controls. These results have important implications in helping to understand the complex profile of visual perceptual difficulties associated with CVI.},
	keywords = {Attention, Brain Diseases, Eye Movements, Fixation, Ocular, Humans, Vision Disorders, Visual Perception},
	issn = {1872-7131},
	doi = {10.1016/j.braindev.2023.05.001},
	author = {Manley, Claire E and Walter, Kerri and Micheletti, Serena and Tietjen, Matthew and Cantillon, Emily and Fazzi, Elisa M and Bex, Peter J and Merabet, Lotfi B}
}
@article {1647897,
	title = {Assessing Higher-Order Visual Processing in Cerebral Visual Impairment Using Naturalistic Virtual-Reality-Based Visual Search Tasks},
	journal = {Children (Basel)},
	volume = {9},
	number = {8},
	year = {2022},
	month = {2022 Jul 26},
	abstract = {Cerebral visual impairment (CVI) is a brain-based disorder associated with the maldevelopment of central visual pathways. Individuals with CVI often report difficulties with daily visual search tasks such as finding a favorite toy or familiar person in cluttered and crowded scenes. We developed two novel virtual reality (VR)-based visual search tasks combined with eye tracking to objectively assess higher order processing abilities in CVI. The first (virtual toybox) simulates a static object search, while the second (virtual hallway) represents a dynamic human search task. Participants were instructed to search for a preselected target while task demand was manipulated with respect to the presence of surrounding distractors. We found that CVI participants (when compared to age-matched controls) showed an overall impairment with visual search on both tasks and with respect to all gaze metrics. Furthermore, CVI participants showed a trend of worsening performance with increasing task demand. Finally, search performance was also impaired in CVI participants with normal/near normal visual acuity, suggesting that reduced stimulus visibility alone does not account for these observations. This novel approach may have important clinical utility in helping to assess environmental factors related to functional visual processing difficulties observed in CVI.},
	issn = {2227-9067},
	doi = {10.3390/children9081114},
	author = {Manley, Claire E and Bennett, Christopher R and Merabet, Lotfi B}
}
@article {1629474,
	title = {A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 4 to 6 Years of Age},
	journal = {Optom Vis Sci},
	year = {2022},
	month = {2022 Jan 24},
	abstract = {SIGNIFICANCE: Binocular treatment for unilateral amblyopia is an emerging treatment that requires evaluation through a randomized clinical trial. PURPOSE: To compare change in amblyopic eye visual acuity (VA) in children aged 4 to 6 years treated with the dichoptic binocular Dig Rush iPad game plus continued spectacle correction vs. continued spectacle correction alone. METHODS: Children (mean 5.7 years) were randomly assigned to home treatment for 8 weeks with the iPad game (n = 92, prescribed 1 hour/day, 5 days/week or continued spectacle correction alone n = 90) in a multi-center randomized clinical trial. Prior to enrollment, children wearing spectacles were required to have at least 16 weeks of wear or no improvement in amblyopic-eye VA (\&lt; 0.1 logMAR) for at least 8 weeks. Outcome was change in amblyopic-eye VA from baseline to 4 weeks (primary) and 8 weeks (secondary) assessed by masked examiner. RESULTS: 182 children with anisometropic (63\%), strabismic (16\%) (\&lt;5[INCREMENT] near, simultaneous prism and cover test), or combined-mechanism (20\%) amblyopia (20/40 to 20/200, mean 20/63) were enrolled. After 4 weeks, mean amblyopic VA improved 1.1 logMAR lines with binocular treatment and 0.6 logMAR lines with spectacles alone (adjusted difference = 0.5 lines; 95.1\% CI: 0.1 to 0.9). After 8 weeks, results (binocular treatment: mean amblyopic-eye VA improvement = 1.3 logMAR lines vs. 1.0 logMAR lines with spectacles alone, adjusted difference = 0.3 lines; 98.4\% CI: -0.2 to 0.8) were inconclusive because the confidence interval included both zero and the pre-defined difference in mean VA change of 0.75 logMAR lines. CONCLUSIONS: In 4- to 6-year-old children with amblyopia, binocular Dig Rush treatment resulted in greater improvement in amblyopic-eye VA over 4 weeks but not 8 weeks. Future work is required to determine if modifications to the contrast increment algorithm or other aspects of the game or its implementation could enhance the treatment effect.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001867},
	author = {Manny, Ruth E and Holmes, Jonathan M and Kraker, Raymond T and Li, Zhuokai and Waters, Amy L and Kelly, Krista R and Kong, Lingkun and Crouch, Earl R and Lorenzana, Ingryd J and Alkharashi, Maan S and Galvin, Jennifer A and Rice, Melissa L and Melia, B Michele and Cotter, Susan A and Pediatric Eye Disease Investigator Group}
}
@article {1402584,
	title = {FGF21 underlies a hormetic response to metabolic stress in methylmalonic acidemia},
	journal = {JCI Insight},
	volume = {3},
	number = {23},
	year = {2018},
	month = {2018 Dec 06},
	abstract = {Methylmalonic acidemia (MMA), an organic acidemia characterized by metabolic instability and multiorgan complications, is most frequently caused by mutations in methylmalonyl-CoA mutase (MUT). To define the metabolic adaptations in MMA in acute and chronic settings, we studied a mouse model generated by transgenic expression of Mut in the muscle. Mut-/-;TgINS-MCK-Mut mice accurately replicate the hepatorenal mitochondriopathy and growth failure seen in severely affected patients and were used to characterize the response to fasting. The hepatic transcriptome in MMA mice was characterized by the chronic activation of stress-related pathways and an aberrant fasting response when compared with controls. A key metabolic regulator, Fgf21, emerged as a significantly dysregulated transcript in mice and was subsequently studied in a large patient cohort. The concentration of plasma FGF21 in MMA patients correlated with disease subtype, growth indices, and markers of mitochondrial dysfunction but was not affected by renal disease. Restoration of liver Mut activity, by transgenesis and liver-directed gene therapy in mice or liver transplantation in patients, drastically reduced plasma FGF21 and was associated with improved outcomes. Our studies identify mitocellular hormesis as a hepatic adaptation to metabolic stress in MMA and define FGF21 as a highly predictive disease biomarker.},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.124351},
	author = {Manoli, Irini and Sysol, Justin R and Epping, Madeline W and Li, Lina and Wang, Cindy and Sloan, Jennifer L and Pass, Alexandra and Gagn{\'e}, Jack and Ktena, Yiouli P and Li, Lingli and Trivedi, Niraj S and Ouattara, Bazoumana and Zerfas, Patricia M and Hoffmann, Victoria and Abu-Asab, Mones and Tsokos, Maria G and Kleiner, David E and Garone, Caterina and Cusmano-Ozog, Kristina and Enns, Gregory M and Vernon, Hilary J and Andersson, Hans C and Grunewald, Stephanie and Elkahloun, Abdel G and Girard, Christiane L and Schnermann, Jurgen and DiMauro, Salvatore and Andres-Mateos, Eva and Vandenberghe, Luk H and Chandler, Randy J and Venditti, Charles P}
}
@article {1460350,
	title = {Chicken Meat-Associated Enterococci: Influence of Agricultural Antibiotic Use and Connection to the Clinic},
	journal = {Appl Environ Microbiol},
	volume = {85},
	number = {22},
	year = {2019},
	month = {2019 Nov 15},
	abstract = {Industrial farms are unique, human-created ecosystems that provide the perfect setting for the development and dissemination of antibiotic resistance. Agricultural antibiotic use amplifies naturally occurring resistance mechanisms from soil ecologies, promoting their spread and sharing with other bacteria, including those poised to become endemic within hospital environments. To better understand the role of enterococci in the movement of antibiotic resistance from farm to table to clinic, we characterized over 300 isolates of cultured from raw chicken meat purchased at U.S. supermarkets by the Consumers Union in 2013. and were the predominant species found, and antimicrobial susceptibility testing uncovered striking levels of resistance to medically important antibiotic classes, particularly from classes approved by the FDA for use in animal production. While nearly all isolates were resistant to at least one drug, bacteria from meat labeled as raised without antibiotics had fewer resistances, particularly for Whole-genome sequencing of 92 isolates revealed that both commensal- and clinical-isolate-like enterococcal strains were associated with chicken meat, including isolates bearing important resistance-conferring elements and virulence factors. The ability of enterococci to persist in the food system positions them as vehicles to move resistance genes from the industrial farm ecosystem into more human-proximal ecologies. Bacteria that contaminate food can serve as a conduit for moving drug resistance genes from farm to table to clinic. Our results show that chicken meat-associated isolates of are often multidrug resistant, closely related to pathogenic lineages, and harbor worrisome virulence factors. These drug-resistant agricultural isolates could thus represent important stepping stones in the evolution of enterococci into drug-resistant human pathogens. Although significant efforts have been made over the past few years to reduce the agricultural use of antibiotics, continued assessment of agricultural practices, including the roles of processing plants, shared breeding flocks, and probiotics as sources for resistance spread, is needed in order to slow the evolution of antibiotic resistance. Because antibiotic resistance is a global problem, global policies are needed to address this threat. Additional measures must be taken to mitigate the development and spread of antibiotic resistance elements from farms to clinics throughout the world.},
	issn = {1098-5336},
	doi = {10.1128/AEM.01559-19},
	author = {Manson, Abigail L and Van Tyne, Daria and Straub, Timothy J and Clock, Sarah and Crupain, Michael and Rangan, Urvashi and Gilmore, Michael S and Earl, Ashlee M}
}
@article {1363149,
	title = {Deprivation amblyopia and congenital hereditary cataract},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {321-6},
	abstract = {Amblyopia is a neurodevelopmental disorder of vision associated with decreased visual acuity, poor or absent stereopsis, and suppression of information from one eye.(1,2) Amblyopia may be caused by strabismus (strabismic amblyopia), refractive error (anisometropic amblyopia), or deprivation from obstructed vision (deprivation amblyopia). 1 In the developed world, amblyopia is the most common cause of childhood visual impairment, 3 which reduces quality of life 4 and also almost doubles the lifetime risk of legal blindness.(5, 6) Successful treatment of amblyopia greatly depends on early detection and treatment of predisposing disorders such as congenital cataract, which is the most common cause of deprivational amblyopia. Understanding the genetic causes of congenital cataract leads to more effective screening tests, early detection and treatment of infants and children who are at high risk for hereditary congenital cataract.},
	keywords = {Amblyopia, Cataract, Humans, Sensory Deprivation},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825289},
	author = {Mansouri, Behzad and Stacy, Rebecca C and Kruger, Joshua and Cestari, Dean M}
}
@article {1319473,
	title = {Rehabilitation of Visual Loss: Where We Are and Where We Need to Be},
	journal = {J Neuroophthalmol},
	volume = {38},
	number = {2},
	year = {2018},
	month = {2018 Jun},
	pages = {223-229},
	abstract = {BACKGROUND: Spontaneous recovery of visual loss resulting from injury to the brain is variable. A variety of traditional rehabilitative strategies, including the use of prisms or compensatory saccadic eye movements, have been used successfully to improve visual function and quality-of-life for patients with homonymous hemianopia. More recently, repetitive visual stimulation of the blind area has been reported to be of benefit in expanding the field of vision. EVIDENCE ACQUISITION: We performed a literature review with main focus on clinical studies spanning from 1963 to 2016, including 52 peer-reviewed articles, relevant cross-referenced citations, editorials, and reviews. RESULTS: Repetitive visual stimulation is reported to expand the visual field, although the interpretation of results is confounded by a variety of methodological factors and conflicting outcomes from different research groups. Many studies used subjective assessments of vision and did not include a sufficient number of subjects or controls. CONCLUSIONS: The available clinical evidence does not strongly support claims of visual restoration using repetitive visual stimulation beyond the time that spontaneous visual recovery might occur. This lack of firm supportive evidence does not preclude the potential of real benefit demonstrated in laboratories. Additional well-designed clinical studies with adequate controls and methods to record ocular fixation are needed.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000594},
	author = {Mansouri, Behzad and Roznik, Marinya and Rizzo, Joseph F and Prasad, Sashank}
}
@article {1195261,
	title = {Ophthalmologic Features of Progeria},
	journal = {Am J Ophthalmol},
	volume = {182},
	year = {2017},
	month = {2017 Oct},
	pages = {126-132},
	abstract = {PURPOSE: To establish the natural history of ophthalmic characteristics in Progeria patients and to determine incidence of ocular manifestations. DESIGN: Retrospective case series of patients with Progeria who were seen between 2007 and 2016. METHODS: Setting: Tertiary-care academic center. PATIENT POPULATION: Fourteen patients (28 eyes) with Hutchinson-Gilford Progeria syndrome were included for statistical analysis from a total of 84 patients who have been enrolled in clinical trials for Progeria at Boston Children{\textquoteright}s Hospital. Clinical treatment trial patients who were not seen at the Department of Ophthalmology at our hospital, but for whom we had detailed clinical ophthalmologic records, were also included. This essentially represents an estimated 20\% of the world{\textquoteright}s known patients with Progeria. Interventions or Observation Procedures: Complete ophthalmic examination. MAIN OUTCOME MEASURES: Visual acuity, stereoacuity, refraction, clinical findings of slit-lamp and dilated fundus examinations. RESULTS: Ophthalmic manifestations noted were hyperopia and signs of ocular surface disease owing to nocturnal lagophthalmos and exposure keratopathy. Additional ophthalmic manifestations included reduced brow hair, madarosis, and reduced accommodation. Most patients had relatively good acuity; however, advanced ophthalmic disease was associated with reduced acuity. CONCLUSIONS: Children with Progeria are at risk for serious ophthalmic complications owing to ocular surface disease. Children with Progeria should have an ophthalmic evaluation at the time of diagnosis and at least yearly after that. Aggressive ocular surface lubrication is recommended, including the use of tape tarsorrhaphy at night.},
	keywords = {Adolescent, Child, Child, Preschool, Corneal Diseases, Eye Diseases, Eyebrows, Eyeglasses, Eyelid Diseases, Female, Follow-Up Studies, Humans, Male, Progeria, Refraction, Ocular, Retrospective Studies, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.07.020},
	author = {Mantagos, Iason S and Kleinman, Monica E and Kieran, Mark W and Gordon, Leslie B}
}
@article {705091,
	title = {An Experimental Animal Model of Photodynamic Optic Nerve Head Injury (PONHI).},
	journal = {Curr Eye Res},
	volume = {41},
	number = {11},
	year = {2016},
	month = {2016 Nov},
	pages = {1498-1506},
	abstract = {PURPOSE: Anterior ischemic optic neuropathy (AION) is the most common cause of non-glaucomatous optic nerve head (ONH) injury among older adults. AION results from a sudden ischemic insult to the proximal portion of the optic nerve, typically leading to visual impairment. Here, we present an experimental model of photodynamically induced ONH injury that can be used to study neuroprotective modalities. METHODS: Intraperitoneal injection of mesoporphyrin IX was followed by photodynamic treatment of the ONH in one eye of Brown-Norway rats; the fellow eye received the reverse sequence as a sham control. Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and visual evoked potential (VEP) recordings were performed at different time points following laser treatment. Immunohistochemistry was used to monitor apoptotic cell death (TUNEL) and macrophage infiltration (CD68). Cytokine levels were evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: FA showed early hyperfluorescence and late leakage of the ONH, while SD-OCT revealed optic nerve edema. No leakage or other abnormalities were detected in control eyes. VEPs were significantly reduced in amplitude and showed prolonged responses compared to sham eyes. The number of apoptotic retinal ganglion cells was elevated one day after laser treatment (13.77 {\textpm} 4.49, p \&lt; 0.01) and peaked on day 7 (57.22 {\textpm} 11.34, p \&lt; 0.01). ONH macrophage infiltration also peaked on day 7 (101.8 {\textpm} 9.8, p \&lt; 0.05). ELISAs performed showed upregulation of macrophage chemoattractant protein-1 and macrophage inflammatory protein-2 on days 3 and 1, respectively. CONCLUSIONS: Photodynamic treatment of the ONH after administration of mesoporphyrin IX leads to macroscopic, histologic, and physiologic evidence of ONH injury. Given the long half-life of mesoporphyrin IX and the ease of intraperitoneal injections, this new model of photodynamically induced ONH injury may be a useful tool for studying optic nerve injury and possible neuroprotective treatments.},
	issn = {1460-2202},
	doi = {10.3109/02713683.2015.1135960},
	author = {Mantopoulos, Dimosthenis and Bouzika, Peggy and Tsakris, Athanassios and Pawlyk, Basil S and Sandberg, Michael A and Miller, Joan W and Rizzo Iii, Joseph F and Vavvas, Demetrios G and Cestari, Dean M}
}
@article {1424810,
	title = {Tolerability and Functionality of a Wireless 24-Hour Ocular Telemetry Sensor in African American Glaucoma Patients},
	journal = {J Glaucoma},
	volume = {28},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {119-124},
	abstract = {PURPOSE: The purpose of the study was to evaluate the tolerability and functionality of a wireless ocular telemetry sensor in African American patients with glaucoma. MATERIALS AND METHODS: In this prospective, observational cohort study, 20 African American patients with primary open angle glaucoma (POAG) were evaluated at the University of Colorado Eye Center. Before lens placement, patients recorded ocular comfort and underwent a baseline eye exam. Following the exam, patients were fitted with a SENSIMED Triggerfish contact lens sensor and data recording device. Patients were sent home and instructed to record their activities in a journal and return in 24 hours. Repeat exams were performed at various time points in clinic before and after lens removal. RESULTS: All 20 patients retained the lens for the 24-hour study period. The patient reported comfort was excellent, with a nadir of mean recorded comfort of 7.05/10. Significant clinical changes were noted in lid/conjunctival erythema, BCVA, refraction, and pachymetry over the course of lens wear. The majority of these changes were improved or resolved by 1 hour after lens removal. Voltage output was significantly greater nocturnally than diurnally (184.79 mV and 71.48 mV, respectively; P\&lt;0.0001). There was no significant change in signal variability or slope over the entire duration of the sleep/wake period based on sleep. CONCLUSIONS: The wireless ocular sensor is well tolerated over a 24-hour period in African American patients with POAG despite transient changes in visual acuity and conjunctival erythema. Clinically usable 24-hour profiles were generated for all patients, with voltage output increasing significantly during periods of sleep.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001141},
	author = {Marando, Catherine M and Mansouri, Kaweh and Kahook, Malik Y and Seibold, Leonard K}
}
@article {1661611,
	title = {Evidence for Complementary and Alternative Therapies to Treat Glaucoma},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {85-91},
	abstract = {Complementary and alternative medicine is used by approximately 5\% of patients with glaucoma, and examples include marijuana, Ginkgo biloba extract, bilberry fruit extract, and acupuncture. Systemic marijuana is not beneficial for glaucoma due to the short duration of action, the lack of evidence that it alters disease progression, and its negative side effect profile. Drops that affect the cannabinoid pathway are still being studied. Ginkgo biloba and bilberry fruit extracts have been shown to decrease oxidative stress and improve perfusion of the optic nerve head. However, these findings are inconsistent throughout the literature and the studies are small, which makes the overall evidence weak. There is no evidence that acupuncture alters glaucoma disease progression or causes a sustained decrease in intraocular pressure. In summary, the literature suggests that there are transient and/or theoretical benefits of complementary and alternative medicine for glaucoma care; however, the overall evidence to support their use is weak.},
	keywords = {Complementary Therapies, Glaucoma, Humans, Intraocular Pressure, Optic Disk, Oxidative Stress},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152704},
	author = {Marando, Catherine M and Chen, Teresa C}
}
@article {1655724,
	title = {Association of Predominantly Peripheral Lesions on Ultra-Widefield Imaging and the Risk of Diabetic Retinopathy Worsening Over Time},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {10},
	year = {2022},
	month = {2022 Oct 01},
	pages = {946-954},
	abstract = {Importance: Ultra-widefield (UWF) imaging improves the ability to identify peripheral diabetic retinopathy (DR) lesions compared with standard imaging. Whether detection of predominantly peripheral lesions (PPLs) better predicts rates of disease worsening over time is unknown. Objective: To determine whether PPLs identified on UWF imaging are associated with increased disease worsening beyond the risk associated with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) score. Design, Setting, and Participants: This cohort study was a prospective, multicenter, longitudinal observational study conducted at 37 US and Canadian sites with 388 participants enrolled between February and December 2015. At baseline and annually through 4 years, 200{\textdegree} UWF-color images were obtained and graded for DRSS at a reading center. Baseline UWF-color and UWF-fluorescein angiography (FA) images were evaluated for the presence of PPL. Data were analyzed from May 2020 to June 2022. Interventions: Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures: Predominantly peripheral lesions were defined as DR lesions with a greater extent outside vs inside the 7 standard ETDRS fields. Primary outcome was disease worsening defined as worsening 2 steps or more on the DRSS or receipt of DR treatment. Analyses were adjusted for baseline DRSS score and correlation between 2 study eyes of the same participant. Results: Data for 544 study eyes with nonproliferative DR (NPDR) were analyzed (182 [50\%] female participants; median age, 62 years; 68\% White). The 4-year disease worsening rates were 45\% for eyes with baseline mild NPDR, 40\% for moderate NPDR, 26\% for moderately severe NPDR, and 43\% for severe NPDR. Disease worsening was not associated with color PPL at baseline (present vs absent: 38\% vs 43\%; HR, 0.78; 95\% CI, 0.57-1.08; P = .13) but was associated with FA PPL at baseline (present vs absent: 50\% vs 31\%; HR, 1.72; 95\% CI, 1.25-2.36; P \&lt; .001). Conclusions and Relevance: Although no association was identified with color PPL, presence of FA PPL was associated with greater risk of disease worsening over 4 years, independent of baseline DRSS score. These results suggest that use of UWF-FA to evaluate retinas peripheral to standard ETDRS fields may improve the ability to predict disease worsening in NPDR eyes. These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes.},
	keywords = {Canada, Cohort Studies, Diabetes Mellitus, Diabetic Retinopathy, Female, Fluorescein Angiography, Humans, Macular Edema, Male, Middle Aged, Prospective Studies},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.3131},
	author = {Marcus, Dennis M and Silva, Paolo S and Liu, Danni and Aiello, Lloyd Paul and Antoszyk, Andrew and Elman, Michael and Friedman, Scott and Glassman, Adam R and Googe, Joseph M and Jampol, Lee Merrill and Martin, Daniel F and Melia, Michele and Preston, Carin M and Wykoff, Charles C and Sun, Jennifer K and DRCR Retina Network}
}
@article {1328896,
	title = {CD163+ macrophages infiltrate axon bundles of postmortem optic nerves with glaucoma},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {256},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {2449-2456},
	abstract = {PURPOSE: Prior research in animal models has shown that macrophages and microglia play an important role in pathogenesis of glaucoma, but the phenotype and distribution of macrophages in human glaucomatous tissue have not been sufficiently characterized. METHODS: We analyzed H\&amp;E, CD68-, and CD163-immunostained slides from 25 formaldehyde-fixed, paraffin-embedded autopsy eyes: 12 control eyes and 13 eyes with glaucoma. The diagnosis of glaucoma was made based on a history of glaucoma as reported in the medical record and histological changes characteristic of glaucoma. Glaucoma cases and controls were matched in terms of age, sex, and race. RESULTS: Qualitative analysis of the conventional outflow pathway and the optic nerve revealed that all eyes contained CD163+ cells but a negligible number of CD68+ cells. CD163+ macrophages infiltrated the trabecular meshwork and surrounded Schlemm{\textquoteright}s canal of normal eyes and eyes with glaucoma, but the pattern was variable and qualitatively similar between groups. In optic nerves of control eyes, CD163+ macrophages were present at low levels and restricted to septa between axon bundles. In glaucomatous optic nerves, the number of CD163+ cells was increased both qualitatively and quantitatively (glaucoma 5.1 {\textpm} 0.6\&nbsp;CD163+ cells/mm, control 2.5 {\textpm} 0.3\&nbsp;CD163+ cells/mm, p\&nbsp;\&lt; 0.001), with CD163+ cells infiltrating axon bundles in cases of both mild and severe diseases. CONCLUSIONS: The increase in CD163+ cell number in eyes with mild and severe glaucoma is the first demonstration of macrophage infiltration in glaucomatous human optic nerves. This finding supports a role for macrophages in glaucoma pathogenesis and progression.},
	keywords = {Aged, Aged, 80 and over, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Autopsy, Female, Glaucoma, Humans, Macrophages, Male, Middle Aged, Optic Nerve, Receptors, Cell Surface, Trabecular Meshwork},
	issn = {1435-702X},
	doi = {10.1007/s00417-018-4081-y},
	author = {Margeta, Milica A and Lad, Eleonora M and Proia, Alan D}
}
@article {1632303,
	title = {Disc Hemorrhages Are Associated With Localized Three-Dimensional Neuroretinal Rim Thickness Progression in Open-Angle Glaucoma},
	journal = {Am J Ophthalmol},
	volume = {234},
	year = {2022},
	month = {2022 Feb},
	pages = {188-198},
	abstract = {PURPOSE: To evaluate the relationship between the occurrence of optic disc hemorrhages (DH) and glaucoma progression as determined by multiple glaucoma testing modalities. DESIGN: Prospective cohort study. METHODS: A longitudinal study was undertaken of 124 open-angle glaucoma patients who had yearly disc photography, visual fields (VFs), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fiber layer (RNFL) thickness scans, and optic nerve volume scans (Spectralis), all performed on the same day over a 5-year period. The minimum distance band (MDB) thickness, a 3-dimensional (3D) neuroretinal rim parameter, was calculated from optic nerve volume scans. Patients were classified as glaucoma progressors or glaucoma nonprogressors using event-based analysis. RESULTS: Of 124 open-angle glaucoma patients, 19 (15.3\%) had 1 or more DHs on yearly disc photographs. Presence of a DH was associated with localized 3D neuroretinal rim thickness progression (superior MDB progression; odds ratio: 3.96; P = .04) but not with global or inferior MDB progression (P = .14 and .81, respectively), DP progression (P = .08), VF progression (P = .45), or RNFL global, inferior, or superior progression (P = .17, .26, and .76, respectively). In the majority of patients with MDB progression (14/17 or 82\%), the progression was noted before or concurrently with the first instance of DH. CONCLUSIONS: Glaucoma progression detected by high-density 3D SD-OCT neuroretinal rim measurements preceded DH occurrence in the majority of patients. These findings support the hypothesis that DHs are indicators of ongoing glaucoma progression rather than discrete events that cause subsequent progression.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.06.021},
	author = {Margeta, Milica A and Ratanawongphaibul, Kitiya and Tsikata, Edem and Zemplenyi, Michele and Ondeck, Courtney L and Kim, Janice and Coleman, Anne L and Yu, Fei and de Boer, Johannes F and Chen, Teresa C}
}
@article {1653572,
	title = {Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma},
	journal = {Immunity},
	volume = {55},
	number = {9},
	year = {2022},
	month = {2022 Sep 13},
	pages = {1627-1644.e7},
	abstract = {The apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Here, we found that in two mouse glaucoma models, microglia transitioned to a neurodegenerative phenotype characterized by upregulation of Apoe and Lgals3 (Galectin-3), which were also upregulated in human glaucomatous retinas. Mice with targeted deletion of Apoe in microglia or carrying the human APOE4 allele were protected from retinal ganglion cell (RGC) loss, despite elevated intraocular pressure (IOP). Similarly to Apoe-/- retinal microglia, APOE4-expressing microglia did not upregulate neurodegeneration-associated genes, including Lgals3, following IOP elevation. Genetic and pharmacologic targeting of Galectin-3 ameliorated RGC degeneration, and Galectin-3 expression was attenuated in human APOE4 glaucoma samples. These results demonstrate that impaired activation of APOE4 microglia is protective in glaucoma and that the APOE-Galectin-3 signaling can be targeted to treat this blinding disease.},
	keywords = {Animals, Apolipoprotein E4, Apolipoproteins E, Disease Models, Animal, Galectin 3, Glaucoma, Humans, Mice, Microglia},
	issn = {1097-4180},
	doi = {10.1016/j.immuni.2022.07.014},
	author = {Margeta, Milica A and Yin, Zhuoran and Madore, Charlotte and Pitts, Kristen M and Letcher, Sophia M and Tang, Jing and Jiang, Shuhong and Gauthier, Christian D and Silveira, Sebastian R and Schroeder, Caitlin M and Lad, Eleonora M and Proia, Alan D and Tanzi, Rudolph E and Holtzman, David M and Krasemann, Susanne and Chen, Dong Feng and Butovsky, Oleg}
}
@article {1773521,
	title = {APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation},
	journal = {Alzheimers Dement},
	volume = {20},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {819-836},
	abstract = {INTRODUCTION: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer{\textquoteright}s disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs). METHODS: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions. RESULTS: We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD.},
	keywords = {Alzheimer Disease, Animals, Apolipoprotein E3, Apolipoprotein E4, Apolipoproteins E, Heparan Sulfate Proteoglycans, Humans, Immunologic Factors, Mice, Phosphorylation},
	issn = {1552-5279},
	doi = {10.1002/alz.13436},
	author = {Marino, Claudia and Perez-Corredor, Paula and O{\textquoteright}Hare, Michael and Heuer, Annie and Chmielewska, Natalia and Gordon, Harper and Chandrahas, Anita S and Gonzalez-Buendia, Lucia and Delgado-Tirado, Santiago and Doan, Tri H and Vanderleest, Timothy E and Arevalo-Alquichire, Said and Obar, Robert A and Ortiz-Cordero, Carolina and Villegas, Andres and Sepulveda-Falla, Diego and Kim, Leo A and Lopera, Francisco and Mahley, Robert and Huang, Yadong and Quiroz, Yakeel T and Arboleda-Velasquez, Joseph F}
}
@article {1351166,
	title = {The ocular surface phenotype of Muc5ac and Muc5b null mice},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {1},
	year = {2014},
	month = {2014 Jan 15},
	pages = {291-300},
	abstract = {PURPOSE: Recent development of mice null for either Muc5ac or Muc5b mucin allows study of their specific roles at the mouse ocular surface. A recent report indicated that Muc5ac null mice show an ocular surface phenotype similar to that seen in dry eye syndrome. The purpose of our study was to determine the effect of lack of Muc5ac or Muc5b on the ocular surface, and to determine if environmental desiccating stress exacerbated a phenotype.

METHODS: Muc5ac null and Muc5b null mice, and their wild-type controls were examined for ocular surface defects by fluorescein staining. The number of goblet cells per area of conjunctival epithelium was counted, and levels of mucin gene expression and genes associated with epithelial stress, keratinization, and differentiation, known to be altered in dry eye syndrome, were assayed. To determine if the null mice would respond more to desiccating stress than their wild-type controls, they were challenged in a controlled environment chamber (CEC) and assessed for changes in fluorescein staining, tear volume, and inflammatory cells within the conjunctival and corneal epithelia.

RESULTS: Unlike the previous study, we found no ocular surface phenotype in the Muc5ac null mice, even after exposure to desiccating environmental stress. Similarly, no ocular surface phenotype was present in the Muc5b null mice, either before or after exposure to a dry environment in the CEC.

CONCLUSIONS: Our results indicate that deleting either the Muc5ac or Muc5b gene is insufficient to create an observable dry eye phenotype on the ocular surface of these mice.},
	keywords = {Animals, Conjunctiva, Cornea, Disease Models, Animal, Dry Eye Syndromes, Gene Expression Regulation, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Mucin 5AC, Mucin-5B, Phenotype, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-13194},
	author = {Marko, Christina Kaiser and Tisdale, Ann S and Spurr-Michaud, Sandra and Evans, Christopher and Gipson, Ilene K}
}
@article {1363150,
	title = {Spdef null mice lack conjunctival goblet cells and provide a model of dry eye},
	journal = {Am J Pathol},
	volume = {183},
	number = {1},
	year = {2013},
	month = {2013 Jul},
	pages = {35-48},
	abstract = {Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sj{\"o}gren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease.},
	keywords = {Animals, Biomarkers, Cell Differentiation, Conjunctiva, Disease Models, Animal, Down-Regulation, Dry Eye Syndromes, Female, Genetic Markers, Goblet Cells, Humans, Immunohistochemistry, Male, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Phenotype, Proto-Oncogene Proteins c-ets, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA, Sjogren{\textquoteright}s Syndrome, Up-Regulation},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2013.03.017},
	author = {Marko, Christina K and Menon, Balaraj B and Chen, Gang and Whitsett, Jeffrey A and Clevers, Hans and Gipson, Ilene K}
}
@article {1263361,
	title = {Conjunctivochalasis: A Systematic Review},
	journal = {Surv Ophthalmol},
	year = {2017},
	month = {2017 Nov 08},
	abstract = {Conjunctivochalasis (CCH) is a conjunctival condition characterized by loose, redundant conjunctival folds, most typically in the inferior bulbar conjunctiva of both eyes. Although CCH is a common cause of ocular irritation and discomfort, especially in the elderly, it is often overlooked in clinical practice. Conjunctivochalasis may be associated with various ocular and non-ocular conditions; however, the most important risk factor is aging. Although often asymptomatic, CCH may cause symptoms related to tear film instability and/or delayed tear clearance. Pathogenesis of CCH remains largely unknown, but may involve different elements such as aged conjunctiva, unstable tear film, mechanical friction, ocular surface inflammation, and delayed tear clearance. Contradictory results have been reported on histopathologic changes in CCH, with some studies showing a normal microscopic structure. For symptomatic CCH, medical treatment may include lubrication and anti-inflammatory medications. For symptomatic patients who fail to respond to medical treatment, a surgical procedure may be considered. Although various surgical procedures have been used for CCH, more often it consists of conjunctival cauterization or excision of the redundant conjunctiva, with or without amniotic membrane transplantation.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2017.10.010},
	author = {Marmalidou, Anna and Kheirkhah, Ahmad and Dana, Reza}
}
@article {1435408,
	title = {Medical and surgical management of conjunctivochalasis},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Apr 19},
	abstract = {Conjunctivochalasis (CCH) is a bilateral conjunctival condition characterized by loose, redundant conjunctival folds, typically in the inferior bulbar conjunctiva. It is a common cause of ocular irritation, especially in older age. For asymptomatic CCH, no treatment is necessary. For treatment of symptomatic CCH, however, a variety of medical and surgical approaches are currently available, which will be thoroughly appraised in this review article. The first step in the management is medical therapy, which involves enhanced lubrication and use of anti-inflammatory medications. In refractory cases, a surgical approach may be undertaken for symptom relief. Several techniques have been described for this, with varying success rates. These include conjunctival cauterization, conjunctival excision, scleral fixation of the conjunctiva, conjunctival ligation, laser conjunctivoplasty, and radiowave electrosurgery. Among these, conjunctival cauterization and excision of the redundant conjunctiva, with or without tissue grafting, have gained popularity.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.04.008},
	author = {Marmalidou, Anna and Palioura, Sotiria and Dana, Reza and Kheirkhah, Ahmad}
}
@article {1559551,
	title = {Impact of Vision Loss on Visual Function Among Elderly Residents in the "Home for the Aged" in India: The Hyderabad Ocular Morbidity in Elderly Study},
	journal = {Transl Vis Sci Technol},
	volume = {9},
	number = {13},
	year = {2020},
	month = {2020 Dec},
	pages = {11},
	abstract = {Purpose: The purpose of this study was to report the association between visual impairment (VI) and self-reported visual difficulty among the elderly in residential care using the Indian Vision Functioning Questionnaire (IND-VFQ-33) psychometrically validated questionnaire. Methods: Participants aged >= 60 years were recruited from 41 homes in Hyderabad in South India. All participants underwent detailed eye examination and interviews. Self-reported visual function was assessed using the IND-VFQ-33 questionnaire. Factor Analysis and Item Response Theory (IRT) models were used for analysis. Multivariable regression models were used to investigate associations between derived global difficulty scores versus severity and causes of VI. Presenting visual acuity worse than 6/18 in the better eye was considered as VI. Results: In total, 867 elderly participants completed the INDVFQ-33. Two latent traits ("daily activities" and "visual symptoms") were identified on factor analysis, each with uniquely loading questions. Participants with VI reported significantly higher daily activities difficulty (6 points higher) and visual symptoms difficulty (1.7 points higher) than those without VI ( \&lt; 0.05). Those with cataract reported the highest daily activities and visual symptoms difficulty (7.6 points and 2.2 points higher, respectively, \&lt; 0.05). Greater severity of VI was associated with increased self-reported difficulty for both factors, and for all causes of VI. Conclusions: We present a psychometrically validated visual questionnaire particularly suited to older adults in residential homes. We show a significant association between cause/severity of VI and difficulty with daily activities and visual symptoms after adjusting for sociodemographic and medical factors. Translational Relevance: Understanding the impact of vision loss on visual functions in the elderly will help in planning and resource allocation for developing early intervention programs for the elderly.},
	issn = {2164-2591},
	doi = {10.1167/tvst.9.13.11},
	author = {Marmamula, Srinivas and Mitchell, William and Zebardast, Nazlee and Locascio, Joseph and Barrenkala, Navya Rekha and Kumbham, Thirupathi Reddy and Modepalli, Satya Brahmanandam and Khanna, Rohit C and Friedman, David S}
}
@article {1549029,
	title = {Near vision impairment among the elderly in residential care-the Hyderabad Ocular Morbidity in Elderly Study (HOMES)},
	journal = {Eye (Lond)},
	volume = {35},
	number = {8},
	year = {2021},
	month = {2021 08},
	pages = {2310-2315},
	abstract = {BACKGROUND/OBJECTIVE: To report on the prevalence and risk factors for near vision impairment (NVI) among the elderly in residential care in Telangana State in India. METHODS: Individuals aged >=60 years were recruited from 41 {\textquoteright}home for the aged{\textquoteright} centres in Hyderabad, India. All participants had complete eye examinations including presenting and best-corrected visual acuity assessment for distance and near. NVI was defined as binocular presenting near vision worse than N8 (6/15) among those who had a normal presenting distance visual acuity of 6/18 in the better eye. RESULTS: Of the 826 participants, the mean age was 74.4 years (standard deviation-8.4 years), 525 (63.6\%) were women, 715 (86.6\%) had at least school education. The prevalence of NVI was 51.2\% (95\% CI: 47.7-54.7) based on presenting vision. On applying multiple logistic regression analysis, the odds of NVI were higher in 80 years and older age (OR: 2.17; 95\% CI: 3.44-13.6). Those with school education (OR: 0.58: 95\% CI: 0.36-0.94) and higher education (OR: 0.38; 95\% CI: 0.21-0.69) had lower odds for NVI. Similarly, those with self-reported diabetes (OR: 0.69; 95\% CI: 0.49-0.97), those using spectacles (OR: 0.09; 95\% CI: 0.05-0.16), and those who had undergone cataract surgery (OR: 0.51; 95\% CI: 0.36-0.74) had lower odds for NVI. CONCLUSIONS: NVI was common among the elderly in residential care in homes for the aged in Hyderabad, India. As most of this NVI is correctable, a routine screening programme and dispensing of spectacles can be undertaken to address this vision loss.},
	keywords = {Aged, Cross-Sectional Studies, Eyeglasses, Female, Humans, India, Morbidity, Prevalence, Vision Disorders, Visual Acuity},
	issn = {1476-5454},
	doi = {10.1038/s41433-020-01243-w},
	author = {Marmamula, Srinivas and Barrenkala, Navya Rekha and Khanna, Rohit C and Challa, Rajesh and Bhakki, Madhuri and Kumbham, Thirupathi Reddy and Modepalli, Satya Brahmanandam and Yellapragada, Ratnakar and Friedman, David S}
}
@article {1653596,
	title = {Impact of an intervention for avoidable vision loss on visual function in the elderly-The Hyderabad Ocular Morbidity in Elderly Study (HOMES)},
	journal = {Eye (Lond)},
	volume = {37},
	number = {8},
	year = {2023},
	month = {2023 Jun},
	pages = {1725-1731},
	abstract = {BACKGROUND/OBJECTIVES: To report the impact of interventions for avoidable vision impairment (VI) on the visual function of elderly residents in {\textquoteright}homes for the aged{\textquoteright} in India. METHODS: Participants aged >=60 years were recruited. A comprehensive eye examination was conducted by trained examiners and interventions were provided. Trained social investigators administered the Indian Vision Function questionnaire (INDVFQ) to assess visual function before and after the intervention (spectacles, cataract surgery or laser capsulotomy). Lower scores on IVFQ imply better visual function. VI was defined as presenting visual acuity worse than 6/18 in the better eye. VI due to cataract, uncorrected refractive errors, and posterior capsular opacification after cataract surgery were considered avoidable VI. RESULTS: The mean age of the participants (n = 613) was 73.8 years (standard deviation: 8.1 years) and 378 (62.2\%) were women. 64/103 (62.1\%) participants who had avoidable VI at baseline were evaluated after the intervention. Significant gains were observed in all four domains of visual function. There was a 14.9\% improvement in mobility scores (33.8 versus 28.8; p = 0.03), a 19.9\% improvement in the activity limitations score (36.8 versus 29.5; p \&lt; 0.01), a 10.9\% improvement in the psychosocial impact score (41.1 versus 36.6; p \&lt; 0.01) and a 13.6\% improvement in the visual symptoms score (49.2 versus 42.5 p \&lt; 0.01). Overall, the mean IVFQ score improved by 16.4\% (47.6 versus 39.8; p \&lt; 0.01). CONCLUSION: Elderly individuals in residential care with avoidable VI had a significant improvement in visual function after relatively low-cost interventions\&nbsp;such as spectacles and cataract surgery. Strategies are needed to provide these interventions\&nbsp;for the\&nbsp;elderly in {\textquoteright}homes for the aged{\textquoteright}\&nbsp;in India.},
	keywords = {Aged, Capsule Opacification, Cataract, Cataract Extraction, Female, Humans, India, Male, Morbidity, Prevalence, Refractive Errors, Vision Disorders},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-02229-6},
	author = {Marmamula, Srinivas and Barrenkala, Navya Rekha and Kumbham, Thirupathi Reddy and Modepalli, Satya Brahmanandam and Yellapragada, Ratnakar and Khanna, Rohit C and Friedman, David S}
}
@article {1528412,
	title = {Falls and visual impairment among elderly residents in {\textquoteright}homes for the aged{\textquoteright} in India},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Aug 07},
	pages = {13389},
	abstract = {We evaluated the prevalence of falls and their association with visual impairment (VI) in elderly residents in {\textquoteright}homes for the aged{\textquoteright} in Hyderabad, India. Participants aged >= 60\&nbsp;years were recruited from 41 homes, and a comprehensive eye examination was conducted. Interviews were conducted to collect personal and demographic information, systemic health status, fear of falling, depression, and history of falls in the last year. VI categories included low vision (presenting visual acuity worse than 6/18 to 3/60) and blindness (presenting visual acuity worse than 3/60). The data of 1,074 participants were analysed. The mean age was 74.4\&nbsp;years (standard deviation:8.7\&nbsp;years); 63.9\% were women, 19.4\% had no formal education, 28.1\% were diabetic and 56.9\% were hypertensive. The annual prevalence of falls was 29.1\% (95\% CI: 26.4-32.0). Multivariable analysis showed those with VI had significantly higher odds of falls (Odds Ratio:1.47; p = 0.043). The prevalence of falls was higher among those with VI due to uncorrected refractive errors. We found a very high prevalence of falls in elderly individuals living in {\textquoteright}homes for the aged{\textquoteright} in Hyderabad, India. Addressing VI can result in fewer falls and contribute to healthy aging in India.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-70066-2},
	author = {Marmamula, Srinivas and Barrenkala, Navya Rekha and Challa, Rajesh and Kumbham, Thirupathi Reddy and Modepalli, Satya Brahmanandam and Yellapragada, Ratnakar and Bhakki, Madhuri and Friedman, David S and Khanna, Rohit C}
}
@article {1528429,
	title = {Visual outcomes after cataract surgery among the elderly residents in the {\textquoteright}homes for the aged{\textquoteright} in South India: the Hyderabad Ocular Morbidity in Elderly Study},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {1087-1093},
	abstract = {BACKGROUND/AIM: To report visual outcomes and factors associated with good visual outcomes after cataract surgery among the elderly residents in {\textquoteright}homes for the aged{\textquoteright} in Hyderabad, India. METHODS: Individuals aged >=60\&nbsp;years were recruited from 41 {\textquoteright}homes for the aged{\textquoteright}. All participants had a detailed eye examinations including visual acuity (VA) assessment , refraction, slit-lamp examination and fundus imaging by trained professionals. A detailed history of cataract surgery was recorded. Multivariate logistic regression was used to determine the factors associated with good visual outcomes after cataract surgery which was defined as presenting VA of 6/18 or better in the operated eye. Visual impairment (VI) is defined as presenting VA worse than 6/18 in the operated eye. RESULTS: 1215 eyes of 703 individuals had cataract surgery. The mean age of these participants was 77.5\&nbsp;years (SD: 8.2\&nbsp;years; range: 60-108\&nbsp;years), 66.8\% were women, 29.9\% reported diabetes and 61\% reported hypertension. 406/1215 (33.4\%; 95\% CI 30.8 to 36.1) eyes had VI after cataract surgery. Posterior capsular opacification (31.8\%; n=129) was the leading cause of VI followed by uncorrected refractive error (24.1\%; n=98). The prevalence of good outcomes was 66.6\% (95\% CI 63.8 to 69.2). On applying multivariable analysis, younger age, self-reported hypertension, independent mobility, surgery in a non-government (as opposed to private) hospital and undergoing paid surgery were associated with good outcomes. CONCLUSIONS: One-third of the eyes of elderly individuals living in homes for the aged that had previously undergone cataract surgery had VI. Regular eye examinations with the provision of laser capsulotomy and appropriate refractive correction can substantially improve their vision.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-317167},
	author = {Marmamula, Srinivas and Barrenakala, Navya Rekha and Challa, Rajesh and Kumbham, Thirupathi Reddy and Modepalli, Satya Brahmanandam and Yellapragada, Ratnakar and Bhakki, Madhuri and Reddy, Jagadesh C and Friedman, David S and Khanna, Rohit C}
}
@article {1498241,
	title = {Uncorrected refractive errors for distance among the residents in {\textquoteright}homes for the aged{\textquoteright} in South India-The Hyderabad Ocular Morbidity in Elderly Study (HOMES)},
	journal = {Ophthalmic Physiol Opt},
	volume = {40},
	number = {3},
	year = {2020},
	month = {2020 May},
	pages = {343-349},
	abstract = {PURPOSE: To investigate the prevalence and risk factors of Uncorrected Refractive Errors (URE) for distance in elderly residents in {\textquoteright}homes for the aged{\textquoteright} in Hyderabad, India. METHODS: Individuals aged >=60\&nbsp;years and residing in {\textquoteright}homes for the aged{\textquoteright} in Hyderabad, India for a minimum of 1\&nbsp;month and providing consent for participation were recruited. All participants underwent visual acuity assessment, refraction, slit lamp biomicroscopy, intraocular pressure measurement, fundus examination, and retinal imaging. Monocular presenting visual acuity was recorded using a logMAR chart. Objective and subjective refraction were performed, and best-corrected visual acuity was recorded. URE was defined as presenting visual acuity worse than 6/12 but improving to 6/12 or better with refraction. Univariable and multivariable logistic regression analyses were used to assess the risk factors associated with URE. RESULTS: In total, 1\&nbsp;513 elderly participants were enumerated from 41 homes of which 1\&nbsp;182 participants (78.1\%) were examined. The mean age of participants was 75.0\&nbsp;years (standard deviation 8.8\&nbsp;years; range: 60-108\&nbsp;years). 35.4\% of those examined were men and 20.3\% had no formal education. The prevalence of URE was 13.5\% (95\% CI: 11.5-15.5; n\&nbsp;=\&nbsp;159). On applying multiple logistic regression analysis, compared to those living in private homes, the odds of URE were significantly higher among the elderly living in the aided homes (OR: 1.65; 95\% CI: 1.11-2.43) and free homes (OR: 1.67; 95\% CI: 1.00-2.80). As compared to those who reported having an eye examination in the last 3\&nbsp;years, the odds of URE were higher among those who never had an eye examination in the last three years (OR: 1.51; 95\% CI: 1.07-2.14). Similarly, those who had unilateral cataract surgery (OR: 1.80; 95\% CI: 1.10-2.93) or bilateral cataract surgery (1.69; 95\% CI: 1.10-2.56) had higher odds of URE compared to those elderly who were not operated\&nbsp;for cataract. Gender, self-report of diabetes, and education were not associated with URE. CONCLUSIONS: A large burden of URE was found among the residents in the {\textquoteright}homes for the aged{\textquoteright} in Hyderabad, India which could be addressed with a pair of glasses. Over 40\% of the residents never had an eye examination in the last three years, which indicates poor utilisation of eye care services by the elderly. Regular eye examinations and provision of spectacles are needed to address needless URE for distance among the elderly in residential care in India.},
	issn = {1475-1313},
	doi = {10.1111/opo.12684},
	author = {Marmamula, Srinivas and Barrenkala, Navya Rekha and Challa, Rajesh and Kumbam, Thirupathi Reddy and Modepalli, Satya Brahmanandam and Yellapragada, Ratnakar and Bhakki, Madhuri and Khanna, Rohit C and Friedman, David S}
}
@article {1498238,
	title = {Prevalence and risk factors for visual impairment among elderly residents in {\textquoteright}homes for the aged{\textquoteright} in India: the Hyderabad Ocular Morbidity in Elderly Study (HOMES)},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {32-36},
	abstract = {BACKGROUND/AIM: To investigate the prevalence, causes and risk factors of visual impairment (VI) among the elderly in {\textquoteright}home for the aged{\textquoteright} in Hyderabad, India. METHODS: Individuals aged >=60 years were recruited from 41 {\textquoteright}homes for the aged{\textquoteright}. All participants had complete eye examinations including presenting visual acuity, refraction, slit-lamp examination, intraocular pressure measurement and fundus imaging by trained clinicians. VI was defined as presenting visual acuity worse than 6/18 in the better eye. Multivariate logistic regression was used to determine the risk factors associated with VI. RESULTS: 1512 elderly residents from 41 homes for the aged were enumerated, of whom 1182 (78.1\%) were examined. The mean age of examined participants was 75.0 years (SD 8.8 years; range: 60-108 years); 35.4\% of those examined were men. The prevalence of VI was 30.1\% (95\% CI 27.5 to 32.8). The leading cause of VI was cataract (46.3\%, n=165), followed by uncorrected refractive error (27.0\%, n=96), posterior capsular opacification (14.9\%, n=53) and posterior segment disease (6.5\%, n=23). Overall, 88.2\% of the VI was either treatable or correctable. In multiple logistic regression, those aged 80 years and older (OR: 1.7, p\&lt;0.01), living in {\textquoteright}free{\textquoteright} homes (OR: 1.5, p\&lt;0.01) and who were immobile/bedridden (OR: 3.02, p\&lt;0.01) had significantly higher odds of VI. Gender was not associated with VI. CONCLUSIONS: VI was common and largely avoidable in residents of {\textquoteright}homes for the aged{\textquoteright} in Hyderabad, India. Screening for vision loss in {\textquoteright}homes for aged{\textquoteright} and the provision of appropriate services should become routine practice to achieve the goal of healthy ageing in India.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-315678},
	author = {Marmamula, Srinivas and Barrenakala, Navya Rekha and Challa, Rajesh and Kumbham, Thirupathi Reddy and Modepalli, Satya Brahmanandam and Yellapragada, Ratnakar and Bhakki, Madhuri and Khanna, Rohit C and Friedman, David S}
}
@article {1470972,
	title = {Validation of RetmarkerAMD as a semiautomatic grading software for AMD},
	journal = {Eye (Lond)},
	volume = {34},
	number = {3},
	year = {2020},
	month = {2020 Mar},
	pages = {600-602},
	issn = {1476-5454},
	doi = {10.1038/s41433-019-0624-7},
	author = {Marques, Jo{\~a}o Pedro and Pires, Jo{\~a}o and Sim{\~a}o, Jorge and Marques, Marco and Gil, Jo{\~a}o Q and La{\'\i}ns, In{\^e}s and Alves, Dalila and Nunes, Sandrina and Cachulo, Maria Luz and Miller, John B and Vavvas, Demetrios G and Miller, Joan W and Husain, Deeba and Silva, Rufino}
}
@article {314161,
	title = {Tuning and disrupting the brain-modulating the McGurk illusion with electrical stimulation.},
	journal = {Front Hum Neurosci},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {533},
	abstract = {In the so-called McGurk illusion, when the synchronized presentation of the visual stimulus /ga/ is paired with the auditory stimulus /ba/, people in general hear it as /da/. Multisensory integration processing underlying this illusion seems to occur within the Superior Temporal Sulcus (STS). Herein, we present evidence demonstrating that bilateral cathodal transcranial direct current stimulation (tDCS) of this area can decrease the McGurk illusion-type responses. Additionally, we show that the manipulation of this audio-visual integrated output occurs irrespective of the number of eye-fixations on the mouth of the speaker. Bilateral anodal tDCS of the Parietal Cortex also modulates the illusion, but in the opposite manner, inducing more illusion-type responses. This is the first demonstration of using non-invasive brain stimulation to modulate multisensory speech perception in an illusory context (i.e., both increasing and decreasing illusion-type responses to a verbal audio-visual integration task). These findings provide clear evidence that both the superior temporal and parietal areas contribute to multisensory integration processing related to speech perception. Specifically, STS seems fundamental for the temporal synchronization and integration of auditory and visual inputs. For its part, posterior parietal cortex (PPC) may adjust the arrival of incoming audio and visual information to STS thereby enhancing their interaction in this latter area.},
	issn = {1662-5161},
	doi = {10.3389/fnhum.2014.00533},
	author = {Marques, Lucas Murrins and Lapenta, Olivia Morgan and Merabet, Lotfi B and Bolognini, Nadia and Boggio, Paulo S{\'e}rgio}
}
@article {1363151,
	title = {Indications and techniques of endoscope assisted vitrectomy},
	journal = {J Ophthalmic Vis Res},
	volume = {8},
	number = {3},
	year = {2013},
	month = {2013 Jul},
	pages = {282-90},
	abstract = {The popularization of ophthalmic endoscopy has been promoted by recent technological advancements that increase the number of indications for endoscopy. These advancements have improved the endoscope{\textquoteright}s capabilities in its two fundamental surgical advantages: (1) bypassing anterior segment opacities, and (2) visualizing anteriorly positioned structures such as the ciliary bodies and sub-iris space. In this article, the current state of the ophthalmic endoscope is reviewed alongside its growing number of applications in glaucoma, vitreoretinal, and ocular trauma surgery. We describe the role of endoscopy in endocyclophotocoagulation for glaucoma, cyclitic membrane peeling in hypotony, retinal detachment surgery, intraocular foreign body removal, severe endophthalmitis, and pediatric traumatic vitreoretinal surgery. This review examines both the pearls and limitations of the ophthalmic application of endoscopy. In doing so, we hope to provide guidelines for using the endoscope and also to highlight applications of endoscopy that merit further study.},
	issn = {2008-2010},
	author = {Marra, Kyle V and Yonekawa, Yoshihiro and Papakostas, Thanos D and Arroyo, Jorge G}
}
@article {369041,
	title = {Case-matched comparison of vitrectomy, peripheral retinal endolaser, and endocyclophotocoagulation versus standard care in neovascular glaucoma.},
	journal = {Retina},
	volume = {35},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {1072-83},
	abstract = {PURPOSE: To evaluate the efficacy of combination pars plana vitrectomy, endoscopic peripheral panretinal photocoagulation, and endocyclophotocoagulation (ECP) as compared with standard care in patients with neovascular glaucoma. METHODS: This age-matched case-controlled retrospective series of 54 eyes compared the clinical outcomes between a consecutive series of combination pars plana vitrectomy/panretinal photocoagulation/ECP (n = 27) versus the current standard of care (n = 27) for patients with neovascular glaucoma. "Standard" treatments for patients with neovascular glaucoma include panretinal photocoagulation, intravitreal bevacizumab, filtration surgery, pars plana vitrectomy, and Ahmed valve placement. RESULTS: After 1 year, mean intraocular pressure reduced from 40.7 {\textpm} 12.40 mmHg preoperatively to 12.3 {\textpm} 4.84 mmHg (P \&lt; 0.001) in the ECP group and from 34.7 {\textpm} 12.38 mmHg to 23.2 {\textpm} 12.34 mmHg in the control group (P = 0.002). Compared with controls, the mean drop in intraocular pressure in the ECP group was significantly greater at all postoperative visits. Logarithm of the minimal angle of resolution visual acuity outcomes were similar in both groups. There were 2 cases (7.4\%) of postoperative phthisis bulbi in each group. CONCLUSION: Endoscopic pars plana vitrectomy, panretinal photocoagulation, and ECP seem to control intraocular pressure to a greater extent than standard glaucoma treatments in patients with neovascular glaucoma. In this aged-matched comparative case series, there was no significant difference between the two treatments{\textquoteright} effects on visual acuity.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000449},
	author = {Marra, Kyle V and Wagley, Sushant and Omar, Ahmed and Kinoshita, Taiga and Kovacs, Kyle D and Silva, Paolo and Kuperwaser, Mark C and Arroyo, Jorge G}
}
@article {1233381,
	title = {DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome},
	journal = {Hum Mutat},
	volume = {39},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {23-39},
	abstract = {The deleted in colorectal cancer (DCC) gene encodes the netrin-1 (NTN1) receptor DCC, a transmembrane protein required for the guidance of commissural axons. Germline DCC mutations disrupt the development of predominantly commissural tracts in the central nervous system (CNS) and cause a spectrum of neurological disorders. Monoallelic, missense, and predicted loss-of-function DCC mutations cause congenital mirror movements, isolated agenesis of the corpus callosum (ACC), or both. Biallelic, predicted loss-of-function DCC mutations cause developmental split brain syndrome (DSBS). Although the underlying molecular mechanisms leading to disease remain poorly understood, they are thought to stem from reduced or perturbed NTN1 signaling. Here, we review the 26 reported DCC mutations associated with abnormal CNS development in humans, including 14 missense and 12 predicted loss-of-function mutations, and discuss their associated clinical characteristics and diagnostic features. We provide an update on the observed genotype-phenotype relationships of congenital mirror movements, isolated ACC and DSBS, and correlate this to our current understanding of the biological function of DCC in the development of the CNS. All mutations and their associated phenotypes were deposited into a locus-specific LOVD (https://databases.lovd.nl/shared/genes/DCC).},
	issn = {1098-1004},
	doi = {10.1002/humu.23361},
	author = {Marsh, Ashley Pl and Edwards, Timothy J and Galea, Charles and Cooper, Helen M and Engle, Elizabeth C and Jamuar, Saumya S and M{\'e}neret, Aur{\'e}lie and Moutard, Marie-Laure and Nava, Caroline and Rastetter, Agn{\`e}s and Robinson, Gail and Rouleau, Guy and Roze, Emmanuel and Spencer-Smith, Megan and Trouillard, Oriane and de Villemeur, Thierry Billette and Walsh, Christopher A and Yu, Timothy W and IRC5 Consortium and Heron, Delphine and Sherr, Elliott H and Richards, Linda J and Depienne, Christel and Leventer, Richard J and Lockhart, Paul J}
}
@article {341746,
	title = {Quantitative autofluorescence as a clinical tool for expedited differential diagnosis of retinal degeneration.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {2},
	year = {2015},
	month = {2015 Feb 1},
	pages = {219-20},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.4507},
	author = {Marsiglia, Marcela and Lee, Winston and Mahajan, Vinit B and Zernant, Jana and Delori, Fran{\c c}ois C and Tsang, Stephen H and Sparrow, Janet R}
}
@article {1626109,
	title = {Neuroradiologic Imaging of Neurologic and Neuro-Ophthalmic Complications of Coronavirus-19 Infection},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {4},
	year = {2021},
	month = {2021 12 01},
	pages = {452-460},
	abstract = {BACKGROUND: To review the literature and provide a summary of COVID-19-related neurologic and neuro-ophthalmic complications. METHODS: The currently available literature was reviewed on PubMed and Google Scholar using the following keywords for searches: CNS, Neuro-Ophthalmology, COVID-19, SARS-CoV-2, coronavirus, optic neuritis, pseudotumor cerebri, Acute Disseminated Encephalomyelitis, posterior reversible encephalopathy syndrome (PRES), meningitis, encephalitis, acute necrotizing hemorrhagic encephalopathy, and Guillain-Barr{\'e} and Miller Fisher syndromes. RESULTS: Neuroradiologic findings of neurologic and neuro-ophthalmologic complications in relationship to COVID-19 infection were reviewed. Afferent visual pathway-related disorders with relevant imaging manifestations included fundus nodules on MRI, papilledema and pseudotumor cerebri syndrome, optic neuritis, Acute Disseminated Encephalomyelitis, vascular injury with thromboembolism and infarct, leukoencephalopathy, gray matter hypoxic injury, hemorrhage, infectious meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and PRES. Efferent visual pathway-related complications with relevant imaging manifestations were also reviewed, including orbital abnormalities, cranial neuropathy, Guillain-Barr{\'e} and Miller Fisher syndromes, and nystagmus and other eye movement abnormalities related to rhombencephalitis. CONCLUSION: COVID-19 can cause central and peripheral nervous system disease, including along both the afferent and efferent components of visual axis. Manifestations of disease and long-term sequela continue to be studied and described. Familiarity with the wide variety of neurologic, ophthalmic, and neuroradiologic presentations can promote prompt and appropriate treatment and continue building a framework to understand the underlying mechanism of disease.},
	keywords = {Brain, COVID-19, Eye, Humans, Magnetic Resonance Imaging, Neuroimaging, Optic Neuritis, Papilledema},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001454},
	author = {Marsiglia, Marcela and Chwalisz, Bart K and Maher, Mary}
}
@article {1806561,
	title = {Presence of Copy Number Variants Associated With Esotropia in Patients With Exotropia},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {243-247},
	abstract = {IMPORTANCE: Strabismus is a common ocular disorder of childhood. There is a clear genetic component to strabismus, but it is not known if esotropia and exotropia share genetic risk factors. OBJECTIVE: To determine whether genetic duplications associated with esotropia are also associated with exotropia. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study conducted from November 2005 to December 2023. Individuals with constant or intermittent exotropia of any magnitude or a history of surgery for exotropia were recruited from pediatric ophthalmic practices. Data were analyzed from March to December 2023. EXPOSURE: Genetic duplication. MAIN OUTCOMES AND MEASURES: Presence of genetic duplications at 2p11.2, 4p15.2, and 10q11.22 assessed by digital droplet polymerase chain reaction. Orthoptic measurements and history of strabismus surgery were performed. RESULTS: A total of 234 individuals (mean [SD] age, 19.5 [19.0] years; 127 female [54.3\%]) were included in this study. The chromosome 2 duplication was present in 1.7\% of patients with exotropia (4 of 234; P = .40), a similar proportion to the 1.4\% of patients with esotropia (23 of 1614) in whom it was previously reported and higher than the 0.1\% of controls (4 of 3922) previously reported (difference, 1.6\%; 95\% CI, 0\%-3.3\%; P \&lt; .001). The chromosome 4 duplication was present in 3.0\% of patients with exotropia (7 of 234; P = .10), a similar proportion to the 1.7\% of patients with esotropia (27 of 1614) and higher than the 0.2\% of controls (6 of 3922) in whom it was previously reported (difference, 2.8\%; 95\% CI, 0.6\%-5.0\%; P \&lt; .001). The chromosome 10 duplication was present in 6.0\% of patients with exotropia (14 of 234; P = .08), a similar proportion to the 4\% of patients with esotropia (64 of 1614) and higher than the 0.4\% of controls (18 of 3922) in whom it was previously reported (difference, 5.6\%; 95\% CI, 2.5\%-8.6\%; P \&lt; .001). Individuals with a duplication had higher mean (SD) magnitude of deviation (31 [13] vs 22 [14] prism diopters [PD]; difference, 9 PD; 95\% CI, 1-16 PD; P = .03), were more likely to have constant (vs intermittent) exotropia (70\% vs 29\%; difference, 41\%; 95\% CI, 20.8\%-61.2\%; P \&lt; .001), and had a higher rate of exotropia surgery than those without a duplication (58\% vs 34\%; difference, 24\%; 95\% CI, 3\%-44\%; P = .02). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, results suggest that the genetic duplications on chromosomes 2, 4, and 10 were risk factors for exotropia as well as esotropia. These findings support the possibility that esotropia and exotropia have shared genetic risk factors. Whether esotropia or exotropia develops in the presence of these duplications may be influenced by other shared or independent genetic variants or by environmental factors.},
	keywords = {Adult, Child, Cross-Sectional Studies, DNA Copy Number Variations, Esotropia, Exotropia, Female, Genotype, Humans, Oculomotor Muscles, Phenotype, Strabismus, Young Adult},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.6782},
	author = {Martinez Sanchez, Mayra and Chan, Wai-Man and MacKinnon, Sarah E and Barry, Brenda and Hunter, David G and Engle, Elizabeth C and Whitman, Mary C}
}
@article {1528425,
	title = {Dynasore protects ocular surface mucosal epithelia subjected to oxidative stress by maintaining UPR and calcium homeostasis},
	journal = {Free Radic Biol Med},
	volume = {160},
	year = {2020},
	month = {2020 Nov 20},
	pages = {57-66},
	abstract = {The mucosal epithelia of the ocular surface protect against external threats to the eye. Using a model of human stratified corneal epithelial cells with mucosal differentiation, we previously demonstrated that a small molecule inhibitor of dynamin GTPases, dynasore, prevents damage to cells and their transcellular barriers when subjected to oxidative stress. Investigating mechanisms, we now report the novel finding that dynasore acts by maintaining Ca homeostasis, thereby inhibiting the PERK branch of the unfolded protein response (UPR) that promotes cell death. Dynasore was found to protect mitochondria by preventing mitochondrial permeability transition pore opening (mPTP), but, unlike reports using other systems, this was not mediated by dynamin family member DRP1. Necrostatin-1, an inhibitor of RIPK1 and lytic forms of programmed cell death, also inhibited mPTP opening and further protected the plasma membrane barrier. Significantly, necrostatin-1 did not protect the mucosal barrier. Oxidative stress increased mRNA for sXBP1, a marker of the IRE1 branch of the UPR, and CHOP, a marker of the PERK branch. It also stimulated phosphorylation of eIF2α, the upstream regulator of CHOP, as well as an increase in intracellular Ca. Dynasore selectively inhibited the increase in PERK branch markers, and also prevented the increase intracellular Ca in response to oxidative stress. The increase in PERK branch markers were also inhibited when cells were treated with the cell permeable Ca chelator, BAPTA-AM. To our knowledge, this is the first time that dynasore has been shown to have an effect on the UPR and suggests therapeutic applications.},
	issn = {1873-4596},
	doi = {10.1016/j.freeradbiomed.2020.07.002},
	author = {Martinez-Carrasco, Rafael and Arg{\"u}eso, Pablo and Fini, M Elizabeth}
}
@article {1417567,
	title = {Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Jan 07},
	abstract = {PURPOSE: To evaluate the therapeutic effect of subconjunctival injection of human mesenchymal stromal cells (hMSCs) in the cornea of mice with graft versus host disease (GVHD). METHODS: GVHD was induced in mice after hematopoietic stem cell transplantation (HSCT) between MHC-mismatched mouse strains. Subconjunctival injection of hMSCs was applied at day 10 post-HSCT. Infiltration of CD3 cells in the cornea and epithelial alterations were analyzed by immunofluorescence. Tear was assessed using the PRT test and TearLab Osmolarity System. qPCR was used to evaluate changes in cytokines, Pax6 and Sprr1b expression. To evaluate the effect of irradiation, we analyzed the expression of these genes in TBI mice. RESULTS: Immune cell invasion occurs in mice with GVHD, as shown by the presence of CD3 cells in the cornea. Interestingly, eyes treated with hMSC did not present CD3 cells. Tear osmolarity was increased in GVHD eyes, but not in treated eyes. TNFa expression was highly increased in all corneas except in Control and treated eyes. Pax6 in corneal epithelium showed a similar pattern in GVHD and Control mice, and its gene expression was enhanced in GVHD corneas. In contrast, Pax6 was reduced in GVHD\&nbsp;+\&nbsp;MSC corneas. We also found an increase in SPRR1B staining in GVHD eyes that was lower in GVHD\&nbsp;+\&nbsp;MSC mice, demonstrating that corneal keratinization is less frequent after treatment with hMSC. CONCLUSIONS: The treatment with hMSCs by subconjunctival injection is effective in reducing corneal inflammation and squamous metaplasia in ocular GVHD (oGVHD). Local treatment with hMSCs is a promising strategy for oGVHD.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.01.001},
	author = {Mart{\'\i}nez-Carrasco, Rafael and S{\'a}nchez-Abarca, Luis Ignacio and Nieto-G{\'o}mez, Cristina and Garc{\'\i}a, Elisabet Mart{\'\i}n and S{\'a}nchez-Guijo, Ferm{\'\i}n and Arg{\"u}eso, Pablo and Aij{\'o}n, Jos{\'e} and Hern{\'a}ndez-Galilea, Emiliano and Velasco, Almudena}
}
@article {1586147,
	title = {Membrane-associated mucins of the human ocular surface in health and disease},
	journal = {Ocul Surf},
	volume = {21},
	year = {2021},
	month = {2021 Jul},
	pages = {313-330},
	abstract = {Mucins are a family of high molecular weight, heavily-glycosylated proteins produced by wet epithelial tissues, including the ocular surface epithelia. Densely-packed O-linked glycan chains added post-translationally confer the biophysical properties of hydration, lubrication, anti-adhesion and repulsion. Membrane-associated mucins (MAMs) are the distinguishing components of the mucosal glycocalyx. At the ocular surface, MAMs maintain wetness, lubricate the blink, stabilize the tear film, and create a physical barrier to the outside world. In addition, it is increasingly appreciated that MAMs function as cell surface receptors that transduce information from the outside to the inside of the cell. Recently, our team published a comprehensive review/perspectives article for molecular scientists on ocular surface MAMs, including previously unpublished data and analyses on two new genes MUC21 and MUC22, as well as new MAM functions and biological roles, comparing human and mouse (PMID: 31493487). The current article is a refocus for the audience of The Ocular Surface. First, we update the gene and protein information in a more concise form, and include a new section on glycosylation. Next, we discuss biological roles, with some new sections and further updating from our previous review. Finally, we provide a new chapter on MAM involvement in ocular surface disease. We end this with discussion of an emerging mechanism responsible for damage to the epithelia and their mucosal glycocalyces: the unfolded protein response (UPR). The UPR offers a novel target for therapeutic intervention.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.03.003},
	author = {Martinez-Carrasco, Rafael and Arg{\"u}eso, Pablo and Fini, M Elizabeth}
}
@article {1623372,
	title = {Corrigendum to "Dynasore protects ocular surface mucosal epithelia subjected to oxidative stress by maintaining UPR and calcium homeostasis" [Free Radic. Biol. Med. 160 (2020) 57-66]},
	journal = {Free Radic Biol Med},
	volume = {179},
	year = {2022},
	month = {2022 Feb 01},
	pages = {421-425},
	issn = {1873-4596},
	doi = {10.1016/j.freeradbiomed.2021.10.030},
	author = {Martinez-Carrasco, Rafael and Arg{\"u}eso, Pablo and Fini, M Elizabeth}
}
@article {1016106,
	title = {Systems neuroscience: Diversity in sight},
	journal = {Nature},
	volume = {542},
	number = {7642},
	year = {2017},
	month = {2017 Feb 23},
	pages = {418-419},
	issn = {1476-4687},
	doi = {10.1038/nature21498},
	author = {Masland, Richard H}
}
@article {1651366,
	title = {Evaluation of the Visual System by the Primary Care Provider Following Concussion},
	journal = {Pediatrics},
	year = {2022},
	author = {Master, CL and Bacal, D and Grady, MF and Hertle, R and Shah, AS and Strominger, M and Whitecross, S and Bradford, GE and Lum, F and Donahue, SP and AAP Section on Ophthalmology and AMERICAN ACADEMY OF OPHTHALMOLOGY and AMERICAN ASSOCIATION FOR PEDIATRIC OPHTHALMOLOGY AND STRABISMUS and AMERICAN ASSOCIATION OF CERTIFIED ORTHOPTISTS}
}
@article {1647868,
	title = {Vision and Concussion: Symptoms, Signs, Evaluation, and Treatment},
	journal = {Pediatrics},
	year = {2022},
	month = {2022 Jul 18},
	abstract = {Visual symptoms are common after concussion in children and adolescents, making it essential for clinicians to understand how to screen, identify, and initiate clinical management of visual symptoms in pediatric patients after this common childhood injury. Although most children and adolescents with visual symptoms after concussion will recover on their own by 4 weeks, for a subset who do not have spontaneous recovery, referral to a specialist with experience in comprehensive concussion management (eg, sports medicine, neurology, neuropsychology, physiatry, ophthalmology, otorhinolaryngology) for additional assessment and treatment may be necessary. A vision-specific history and a thorough visual system examination are warranted, including an assessment of visual acuity, ocular alignment in all positions of gaze, smooth pursuit (visual tracking of a moving object), saccades (visual fixation shifting between stationary targets), vestibulo-ocular reflex (maintaining image focus during movement), near point of convergence (focusing with both eyes at near and accommodation (focusing with one eye at near because any of these functions may be disturbed after concussion. These deficits may contribute to difficulty with returning to both play and the learning setting at school, making the identification of these problems early after injury important for the clinician to provide relevant learning accommodations, such as larger font, preprinted notes, and temporary use of audio books. Early identification and appropriate management of visual symptoms, such as convergence insufficiency or accommodative insufficiency, may mitigate the negative effects of concussion on children and adolescents and their quality of life.},
	issn = {1098-4275},
	doi = {10.1542/peds.2021-056047},
	author = {Master, Christina L and Bacal, Darron and Grady, Matthew F and Hertle, Richard and Shah, Ankoor S and Strominger, Mitchell and Whitecross, Sarah and Bradford, Geoffrey E and Lum, Flora and Donahue, Sean P}
}
@article {1439855,
	title = {Single-cell transcriptomic analysis of Alzheimer{\textquoteright}s disease},
	journal = {Nature},
	volume = {570},
	number = {7761},
	year = {2019},
	month = {2019 Jun},
	pages = {332-337},
	abstract = {Alzheimer{\textquoteright}s disease is a pervasive neurodegenerative disorder, the molecular complexity of which remains poorly understood. Here, we analysed 80,660 single-nucleus transcriptomes from the prefrontal cortex of 48 individuals with varying degrees of Alzheimer{\textquoteright}s disease pathology. Across six major brain cell types, we identified transcriptionally distinct subpopulations, including those associated with pathology and characterized by regulators of myelination, inflammation, and neuron survival. The strongest disease-associated changes appeared early in pathological progression and were highly cell-type specific, whereas genes upregulated at late stages were common across cell types and primarily involved in the global stress response. Notably, we found that female cells were overrepresented in disease-associated subpopulations, and that transcriptional responses were substantially different between sexes in several cell types, including oligodendrocytes. Overall, myelination-related processes were recurrently perturbed in multiple cell types, suggesting that myelination has a key role in Alzheimer{\textquoteright}s disease pathophysiology. Our single-cell transcriptomic resource provides a blueprint for interrogating the molecular and cellular basis of Alzheimer{\textquoteright}s disease.},
	issn = {1476-4687},
	doi = {10.1038/s41586-019-1195-2},
	author = {Mathys, Hansruedi and Davila-Velderrain, Jose and Peng, Zhuyu and Gao, Fan and Mohammadi, Shahin and Young, Jennie Z and Menon, Madhvi and He, Liang and Abdurrob, Fatema and Jiang, Xueqiao and Martorell, Anthony J and Ransohoff, Richard M and Hafler, Brian P and Bennett, David A and Kellis, Manolis and Tsai, Li-Huei}
}
@article {1445332,
	title = {Author Correction: Single-cell transcriptomic analysis of Alzheimer{\textquoteright}s disease},
	journal = {Nature},
	volume = {571},
	number = {7763},
	year = {2019},
	month = {2019 Jul},
	pages = {E1},
	abstract = {Change history: In this Article, the Acknowledgements section should have included that the work was supported in part by the Cure Alzheimer{\textquoteright}s Fund (CAF), and the final NIH grant acknowledged should have been {\textquoteright}U01MH119509{\textquoteright} instead of {\textquoteright}RF1AG054012{\textquoteright}. In Supplementary Table 2, the column labels {\textquoteright}early.pathology.mean{\textquoteright} and {\textquoteright}late.pathology.mean{\textquoteright} were reversed in each worksheet (that is, columns Y and Z). These errors have been corrected online.},
	issn = {1476-4687},
	doi = {10.1038/s41586-019-1329-6},
	author = {Mathys, Hansruedi and Davila-Velderrain, Jose and Peng, Zhuyu and Gao, Fan and Mohammadi, Shahin and Young, Jennie Z and Menon, Madhvi and He, Liang and Abdurrob, Fatema and Jiang, Xueqiao and Martorell, Anthony J and Ransohoff, Richard M and Hafler, Brian P and Bennett, David A and Kellis, Manolis and Tsai, Li-Huei}
}
@article {1351168,
	title = {Strain difference in photoreceptor cell death after retinal detachment in mice},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {7},
	year = {2014},
	month = {2014 May 22},
	pages = {4165-74},
	abstract = {PURPOSE: To evaluate the potential for mouse genetic background to effect photoreceptor cell death in response to experimental retinal detachment (RD). METHODS: Retinal detachment was induced in three inbred mouse strains (C57BL/6, BALB/c, and B6129SF2) by subretinal injection of sodium hyaluronate. A time course of photoreceptor cell death was assessed by TUNEL assay. Total photoreceptor cell death was analyzed through comparing the outer nuclear layer (ONL)/inner nuclear layer (INL) ratio 7 days post RD. Western blot analysis or quantitative real-time PCR (qPCR) were performed to assess cell death signaling, expression of endogenous neurotrophin, and levels of apoptosis inhibitors 24 hours after RD. Inflammatory cytokine secretion and inflammatory cell infiltration were quantified by ELISA and immunostaining, respectively. RESULTS: The peak of photoreceptor cell death after RD was at 24 hours in all strains. Photoreceptor cell death as well as monocyte chemoattractant protein 1 and interleukin 6 secretion at 24 hours after RD was the highest in BALB/c, followed in order of magnitude by C57BL/6 and B6129SF2. Conversely, nerve growth factor expression and ONL/INL ratio were the lowest in BALB/c. Apoptosis signaling was higher in C57BL/6, whereas necroptosis signaling was higher in C57BL/6 and BALB/c. Autophagic signaling was higher in BALB/c. X-linked inhibitor of apoptosis (XIAP) and survivin protein levels were lower in C57BL/6 and BALB/c, respectively. Macrophage/microglia infiltration was higher in C57BL/6 and BALB/c at 24 hours after RD. CONCLUSIONS: Photoreceptor cell death after RD was significantly different among the three strains, suggesting the presence of genetic factors that affect photoreceptor cell death after RD.},
	keywords = {Animals, Apoptosis, Blotting, Western, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Immunohistochemistry, In Situ Nick-End Labeling, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Photoreceptor Cells, Vertebrate, Polysaccharides, Real-Time Polymerase Chain Reaction, Retinal Detachment, RNA, Messenger},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14238},
	author = {Matsumoto, Hidetaka and Kataoka, Keiko and Tsoka, Pavlina and Connor, Kip M and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1363152,
	title = {Retinal detachment model in rodents by subretinal injection of sodium hyaluronate},
	journal = {J Vis Exp},
	number = {79},
	year = {2013},
	month = {2013 Sep 11},
	abstract = {Subretinal injection of sodium hyaluronate is a widely accepted method of inducing retinal detachment (RD). However, the height and duration of RD or the occurrence of subretinal hemorrhage can affect photoreceptor cell death in the detached retina. Hence, it is advantageous to create reproducible RDs without subretinal hemorrhage for evaluating photoreceptor cell death. We modified a previously reported method to create bullous and persistent RDs in a reproducible location with rare occurrence of subretinal hemorrhage. The critical step of this modified method is the creation of a self-sealing scleral incision, which can prevent leakage of sodium hyaluronate after injection into the subretinal space. To make the self-sealing scleral incision, a scleral tunnel is created, followed by scleral penetration into the choroid with a 30 G needle. Although choroidal hemorrhage may occur during this step, astriction with a surgical spear reduces the rate of choroidal hemorrhage. This method allows a more reproducible and reliable model of photoreceptor death in diseases that involve RD such as rhegmatogenous RD, retinopathy of prematurity, diabetic retinopathy, central serous chorioretinopathy, and age-related macular degeneration (AMD). [corrected].},
	keywords = {Animals, Disease Models, Animal, Hyaluronic Acid, Mice, Retinal Detachment},
	issn = {1940-087X},
	doi = {10.3791/50660},
	author = {Matsumoto, Hidetaka and Miller, Joan W and Vavvas, Demetrios G}
}
@article {603936,
	title = {Membrane-bound and soluble Fas ligands have opposite functions in photoreceptor cell death following separation from the retinal pigment epithelium.},
	journal = {Cell Death Dis},
	volume = {6},
	year = {2015},
	month = {2015},
	pages = {e1986},
	abstract = {Fas ligand (FasL) triggers apoptosis of Fas-positive cells, and previous reports described FasL-induced cell death of Fas-positive photoreceptors following a retinal detachment. However, as FasL exists in membrane-bound (mFasL) and soluble (sFasL) forms, and is expressed on resident microglia and infiltrating monocyte/macrophages, the current study examined the relative contribution of mFasL and sFasL to photoreceptor cell death after induction of experimental retinal detachment in wild-type, knockout (FasL-/-), and mFasL-only knock-in (ΔCS) mice. Retinal detachment in FasL-/- mice resulted in a significant reduction of photoreceptor cell death. In contrast, ΔCS mice displayed significantly more apoptotic photoreceptor cell death. Photoreceptor loss in ΔCS mice was inhibited by a subretinal injection of recombinant sFasL. Thus, Fas/FasL-triggered cell death accounts for a significant amount of photoreceptor cell loss following the retinal detachment. The function of FasL was dependent upon the form of FasL expressed: mFasL triggered photoreceptor cell death, whereas sFasL protected the retina, indicating that enzyme-mediated cleavage of FasL determines, in part, the extent of vision loss following the retinal detachment. Moreover, it also indicates that treatment with sFasL could significantly reduce photoreceptor cell loss in patients with retinal detachment.},
	issn = {2041-4889},
	doi = {10.1038/cddis.2015.334},
	author = {Matsumoto, H and Murakami, Y and Kataoka, K and Notomi, S and Mantopoulos, D and Trichonas, G and Miller, J W and Gregory, M S and Ksander, B R and Marshak-Rothstein, A and Vavvas, D G}
}
@article {1351167,
	title = {Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment},
	journal = {Cell Death Dis},
	volume = {5},
	year = {2014},
	month = {2014 May 29},
	pages = {e1269},
	abstract = {Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both cell death and proliferation and a critical factor in development and tumorigenesis. However, to date the role of MST in neurodegeneration has not been fully explored. Utilizing MST1(-/-) and MST2(-/-) mice we identified MST2, but not MST1, as a regulator of photoreceptor cell death in a mouse model of RD. MST2(-/-) mice demonstrated significantly decreased photoreceptor cell death and outer nuclear layer (ONL) thinning after RD. Additionally, caspase-3 activation was attenuated in MST2(-/-) mice compared to control mice after RD. The transcription of p53 upregulated modulator of apoptosis (PUMA) and Fas was also reduced in MST2(-/-) mice post-RD. Retinas of MST2(-/-) mice displayed suppressed nuclear relocalization of phosphorylated YAP after RD. Consistent with the reduction of photoreceptor cell death, MST2(-/-) mice showed decreased levels of proinflammatory cytokines such as monocyte chemoattractant protein 1 and interleukin 6 as well as attenuated inflammatory CD11b cell infiltration during the early phase of RD. These results identify MST2, not MST1, as a critical regulator of caspase-mediated photoreceptor cell death in the detached retina and indicate its potential as a future neuroprotection target.},
	keywords = {Animals, Apoptosis, Caspase 3, Mice, Mice, Knockout, Photoreceptor Cells, Vertebrate, Protein-Serine-Threonine Kinases, Retinal Detachment, Tumor Suppressor Protein p53},
	issn = {2041-4889},
	doi = {10.1038/cddis.2014.218},
	author = {Matsumoto, H and Murakami, Y and Kataoka, K and Lin, H and Connor, K M and Miller, J W and Zhou, D and Avruch, J and Vavvas, D G}
}
@article {1667715,
	title = {Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy},
	journal = {JAMA},
	volume = {329},
	number = {5},
	year = {2023},
	month = {2023 Feb 07},
	pages = {376-385},
	abstract = {IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) injections in eyes with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) reduce development of vision-threatening complications from diabetes over at least 2 years, but whether this treatment has a longer-term benefit on visual acuity is unknown. OBJECTIVE: To compare the primary 4-year outcomes of visual acuity and rates of vision-threatening complications in eyes with moderate to severe NPDR treated with intravitreal aflibercept compared with sham. The primary 2-year analysis of this study has been reported. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 64 clinical sites in the US and Canada from January 2016 to March 2018, enrolling 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study [ETDRS] severity level 43-53; range, 0 [worst] to 100 [best]) without CI-DME. INTERVENTIONS: Eyes were randomly assigned to 2.0 mg aflibercept (n = 200) or sham (n = 199). Eight injections were administered at defined intervals through 2 years, continuing quarterly through 4 years unless the eye improved to mild NPDR or better. Aflibercept was given in both groups to treat development of high-risk proliferative diabetic retinopathy (PDR) or CI-DME with vision loss. MAIN OUTCOMES AND MEASURES: Development of PDR or CI-DME with vision loss (>=10 letters at 1 visit or >=5 letters at 2 consecutive visits) and change in visual acuity (best corrected ETDRS letter score) from baseline to 4 years. RESULTS: Among participants (mean age 56 years; 42.4\% female; 5\% Asian, 15\% Black, 32\% Hispanic, 45\% White), the 4-year cumulative probability of developing PDR or CI-DME with vision loss was 33.9\% with aflibercept vs 56.9\% with sham (adjusted hazard ratio, 0.40 [97.5\% CI, 0.28 to 0.57]; P \&lt; .001). The mean (SD) change in visual acuity from baseline to 4 years was -2.7 (6.5) letters with aflibercept and -2.4 (5.8) letters with sham (adjusted mean difference, -0.5 letters [97.5\% CI, -2.3 to 1.3]; P = .52). Antiplatelet Trialists{\textquoteright} Collaboration cardiovascular/cerebrovascular event rates were 9.9\% (7 of 71) in bilateral participants, 10.9\% (14 of 129) in unilateral aflibercept participants, and 7.8\% (10 of 128) in unilateral sham participants. CONCLUSIONS AND RELEVANCE: Among patients with NPDR but without CI-DME at 4 years treatment with aflibercept vs sham, initiating aflibercept treatment only if vision-threatening complications developed, resulted in statistically significant anatomic improvement but no improvement in visual acuity. Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with NPDR without CI-DME. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02634333.},
	keywords = {Angiogenesis Inhibitors, Diabetic Retinopathy, Female, Humans, Intravitreal Injections, Macular Edema, Male, Middle Aged, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins, Treatment Outcome, Vascular Endothelial Growth Factor A, Vision Disorders, Visual Acuity},
	issn = {1538-3598},
	doi = {10.1001/jama.2022.25029},
	author = {Maturi, Raj K and Glassman, Adam R and Josic, Kristin and Baker, Carl W and Gerstenblith, Adam T and Jampol, Lee M and Meleth, Annal and Martin, Daniel F and Melia, Michele and Punjabi, Omar S and Rofagha, Soraya and Salehi-Had, Hani and Stockdale, Cynthia R and Sun, Jennifer K and DRCR Retina Network}
}
@article {1263366,
	title = {Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {1},
	year = {2018},
	month = {2018 Jan 01},
	pages = {29-38},
	abstract = {Importance: Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. Objective: To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. Design, Setting, and Participants: Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat. Interventions: Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. Main Outcomes and Measures: The primary outcome was change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. Results: Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9\% were female and 60.3\% were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of -0.5 letters (95\% CI, -3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was -110 (86) μm compared with -62 (97) μm for the ranibizumab group (adjusted difference, -52; 95\% CI, -82 to -22; 2-sided P \&lt; .001). Nineteen eyes (29\%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P \&lt; .001). Conclusions and Relevance: Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. Trial Registration: clinicaltrials.gov Identifier: NCT01945866.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.4914},
	author = {Maturi, Raj K and Glassman, Adam R and Liu, Danni and Beck, Roy W and Bhavsar, Abdhish R and Bressler, Neil M and Jampol, Lee M and Melia, Michele and Punjabi, Omar S and Salehi-Had, Hani and Sun, Jennifer K and Diabetic Retinopathy Clinical Research Network}
}
@article {1586140,
	title = {Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {7},
	year = {2021},
	month = {2021 Jul 01},
	pages = {701-712},
	abstract = {Importance: The role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. Objective: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. Design, Setting, and Participants: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. Interventions: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (>=10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. Main Outcomes and Measures: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. Results: Among the 328 participants (57.6\% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3\% with aflibercept vs 43.5\% with sham. The overall hazard ratio for either outcome was 0.32 (97.5\% CI, 0.21-0.50; P \&lt; .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5\% in the aflibercept group vs 33.2\% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1\% in the aflibercept group vs 14.8\% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5\% CI, -1.0 to 1.9 letters]; P = .47). Conclusions and Relevance: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02634333.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.0606},
	author = {Maturi, Raj K and Glassman, Adam R and Josic, Kristin and Antoszyk, Andrew N and Blodi, Barbara A and Jampol, Lee M and Marcus, Dennis M and Martin, Daniel F and Melia, Michele and Salehi-Had, Hani and Stockdale, Cynthia R and Punjabi, Omar S and Sun, Jennifer K and DRCR Retina Network}
}
@article {1318869,
	title = {The Assembly-Activating Protein Promotes Stability and Interactions between AAV{\textquoteright}s Viral Proteins to Nucleate Capsid Assembly},
	journal = {Cell Rep},
	volume = {23},
	number = {6},
	year = {2018},
	month = {2018 May 08},
	pages = {1817-1830},
	abstract = {The adeno-associated virus (AAV) vector is a preferred delivery platform for in\&nbsp;vivo gene therapy. Natural and engineered variations of the AAV capsid affect a plurality of phenotypes relevant to gene therapy, including vector production and host tropism. Fundamental to these aspects is the mechanism of AAV capsid assembly. Here, the role of the viral co-factor assembly-activating protein (AAP) was evaluated in 12 naturally occurring AAVs and 9 putative ancestral capsid intermediates. The results demonstrate increased capsid protein stability and VP-VP\&nbsp;interactions in the presence of AAP. The capsid{\textquoteright}s dependence on AAP can be partly overcome by\&nbsp;strengthening interactions between monomers within the assembly, as illustrated by the transfer of a minimal motif defined by a phenotype-to-phylogeny mapping method. These findings suggest that the emergence of AAP within the Dependovirus genus relaxes structural constraints on AAV assembly in favor of increasing the degrees of freedom for the capsid to evolve.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2018.04.026},
	author = {Maurer, Anna C and Pacouret, Simon and Cepeda Diaz, Ana Karla and Blake, Jessica and Andres-Mateos, Eva and Vandenberghe, Luk H}
}
@article {1417568,
	title = {Residues on Adeno-associated Virus Capsid Lumen Dictate Interactions and Compatibility with the Assembly-Activating Protein},
	journal = {J Virol},
	volume = {93},
	number = {7},
	year = {2019},
	month = {2019 Apr 01},
	abstract = {The adeno-associated virus (AAV) serves as a broadly used vector system for gene delivery. The process of AAV capsid assembly remains poorly understood. The viral cofactor assembly-activating protein (AAP) is required for maximum AAV production and has multiple roles in capsid assembly, namely, trafficking of the structural proteins (VP) to the nuclear site of assembly, promoting the stability of VP against multiple degradation pathways, and facilitating stable interactions between VP monomers. The N-terminal 60 amino acids of AAP (AAPN) are essential for these functions. Presumably, AAP must physically interact with VP to execute its multiple functions, but the molecular nature of the AAP-VP interaction is not well understood. Here, we query how structurally related AAVs functionally engage AAP from AAV serotype 2 (AAP2) toward virion assembly. These studies led to the identification of key residues on the lumenal capsid surface that are important for AAP-VP and for VP-VP interactions. Replacing a cluster of glutamic acid residues with a glutamine-rich motif on the conserved VP beta-barrel structure of variants incompatible with AAP2 creates a gain-of-function mutant compatible with AAP2. Conversely, mutating positively charged residues within the hydrophobic region of AAP2 and conserved core domains within AAPN creates a gain-of-function AAP2 mutant that rescues assembly of the incompatible variant. Our results suggest a model for capsid assembly where surface charge/neutrality dictates an interaction between AAPN and the lumenal VP surface to nucleate capsid assembly. Efforts to engineer the AAV capsid to gain desirable properties for gene therapy (e.g., tropism, reduced immunogenicity, and higher potency) require that capsid modifications do not affect particle assembly. The relationship between VP and the cofactor that facilitates its assembly, AAP, is central to both assembly preservation and vector production. Understanding the requirements for this compatibility can inform manufacturing strategies to maximize production and reduce costs. Additionally, library-based approaches that simultaneously examine a large number of capsid variants would benefit from a universally functional AAP, which could hedge against overlooking variants with potentially valuable phenotypes that were lost during vector library production due to incompatibility with the cognate AAP. Studying interactions between the structural and nonstructural components of AAV enhances our fundamental knowledge of capsid assembly mechanisms and the protein-protein interactions required for productive assembly of the icosahedral capsid.},
	issn = {1098-5514},
	doi = {10.1128/JVI.02013-18},
	author = {Maurer, Anna C and Cepeda Diaz, Ana Karla and Vandenberghe, Luk H}
}
@article {313211,
	title = {Molecular basis for MMP9 induction and disruption of epithelial cell-cell contacts by galectin-3},
	journal = {J Cell Sci},
	volume = {127},
	number = {Pt 14},
	year = {2014},
	month = {2014 Jul 15},
	pages = {3141-8},
	abstract = {Dynamic modulation of the physical contacts between neighboring cells is integral to epithelial processes such as tissue repair and cancer dissemination. Induction of matrix metalloproteinase (MMP) activity contributes to the disassembly of intercellular junctions and the degradation of the extracellular matrix, thus mitigating the physical constraint to cell movement. Using the cornea as a model, we show here that a carbohydrate-binding protein, galectin-3, promotes cell-cell detachment and redistribution of the tight junction protein occludin through its N-terminal polymerizing domain. Notably, we demonstrate that galectin-3 initiates cell-cell disassembly by inducing matrix metalloproteinase expression in a manner that is dependent on the interaction with and clustering of the matrix metalloproteinase inducer CD147 (also known as EMMPRIN and basigin) on the cell surface. Using galectin-3-knockout mice in an in vivo model of wound healing, we further show that increased synthesis of MMP9 at the leading edge of migrating epithelium is regulated by galectin-3. These findings establish a new galectin-3-mediated regulatory mechanism for induction of metalloproteinase expression and disruption of cell-cell contacts required for cell motility in migrating epithelia.},
	keywords = {Animals, Basigin, Cell Communication, Cell Movement, Cells, Cultured, Enzyme Induction, Epithelial Cells, Galectin 3, Humans, Keratinocytes, Matrix Metalloproteinase 9, Mice, Mice, Inbred C57BL, Mice, Knockout, Transfection},
	issn = {1477-9137},
	doi = {10.1242/jcs.148510},
	author = {Mauris, Jerome and Woodward, Ashley M and Cao, Zhiyi and Panjwani, Noorjahan and Arg{\"u}eso, Pablo}
}
@article {1363153,
	title = {Modulation of ocular surface glycocalyx barrier function by a galectin-3 N-terminal deletion mutant and membrane-anchored synthetic glycopolymers},
	journal = {PLoS One},
	volume = {8},
	number = {8},
	year = {2013},
	month = {2013},
	pages = {e72304},
	abstract = {BACKGROUND: Interaction of transmembrane mucins with the multivalent carbohydrate-binding protein galectin-3 is critical to maintaining the integrity of the ocular surface epithelial glycocalyx. This study aimed to determine whether disruption of galectin-3 multimerization and insertion of synthetic glycopolymers in the plasma membrane could be used to modulate glycocalyx barrier function in corneal epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Abrogation of galectin-3 biosynthesis in multilayered cultures of human corneal epithelial cells using siRNA, and in galectin-3 null mice, resulted in significant loss of corneal barrier function, as indicated by increased permeability to the rose bengal diagnostic dye. Addition of β-lactose, a competitive carbohydrate inhibitor of galectin-3 binding activity, to the cell culture system, transiently disrupted barrier function. In these experiments, treatment with a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, but not full-length galectin-3, prevented the recovery of barrier function to basal levels. As determined by fluorescence microscopy, both cellobiose- and lactose-containing glycopolymers incorporated into apical membranes of corneal epithelial cells, independently of the chain length distribution of the densely glycosylated, polymeric backbones. Membrane incorporation of cellobiose glycopolymers impaired barrier function in corneal epithelial cells, contrary to their lactose-containing counterparts, which bound to galectin-3 in pull-down assays. CONCLUSIONS/SIGNIFICANCE: These results indicate that galectin-3 multimerization and surface recognition of lactosyl residues is required to maintain glycocalyx barrier function at the ocular surface. Transient modification of galectin-3 binding could be therapeutically used to enhance the efficiency of topical drug delivery.},
	keywords = {Animals, Biological Transport, Cellobiose, Cells, Cultured, Cornea, Epithelial Cells, Galectin 3, Glycocalyx, Glycoconjugates, Humans, Lactose, Mice, Mice, Knockout, Mucins, Permeability, Protein Multimerization, Protein Structure, Tertiary, Rose Bengal, Structure-Activity Relationship},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0072304},
	author = {Mauris, Jerome and Mantelli, Flavio and Woodward, Ashley M and Cao, Ziyhi and Bertozzi, Carolyn R and Panjwani, Noorjahan and Godula, Kamil and Arg{\"u}eso, Pablo}
}
@article {416886,
	title = {Loss of CD147 results in impaired epithelial cell differentiation and malformation of the meibomian gland.},
	journal = {Cell Death Dis},
	volume = {6},
	year = {2015},
	month = {2015},
	pages = {e1726},
	abstract = {Meibomian gland dysfunction is a leading cause of ocular surface disease. However, little is known about the regulatory processes that control the development and maintenance of this sebaceous gland. Here, we identify a novel function for CD147, a transmembrane protein that promotes tissue remodeling through induction of matrix metalloproteinases, in regulating meibocyte differentiation and activity. We found that CD147 localized along basal cells and within discrete membrane domains of differentiated meibocytes in glandular acini containing gelatinolytic activity. Induction of meibocyte differentiation in vitro promoted CD147 clustering and MMP9 secretion, whereas RNAi-mediated abrogation of CD147 impaired MMP9 secretion, concomitant with a reduction in the number of proliferative cells and cytoplasmic lipids. Meibomian glands of CD147 knockout mice had a lower number of acini in both the superior and inferior tarsal plates of the eyelids, and were characterized by loss of lipid-filled meibocytes compared with control mice. Together, our data provide evidence showing that gelatinolytic activity in meibocytes is dependent on CD147, and supports a role for CD147 in maintaining the normal development and function of the meibomian gland.},
	issn = {2041-4889},
	doi = {10.1038/cddis.2015.98},
	author = {Mauris, J and Dieckow, J and Schob, S and Pulli, B and Hatton, M P and Jeong, S and Bauskar, A and Gabison, E and Nowak, R and Arg{\"u}eso, P}
}
@article {1773431,
	title = {Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration},
	journal = {Neural Regen Res},
	volume = {18},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {2173-2181},
	abstract = {Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration; however, effective treatment is not yet available for geographical atrophy in dry age-related macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human age-related macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.},
	issn = {1673-5374},
	doi = {10.4103/1673-5374.369098},
	author = {Maurya, Meenakshi and Bora, Kiran and Blomfield, Alexandra K and Pavlovich, Madeline C and Huang, Shuo and Liu, Chi-Hsiu and Chen, Jing}
}
@article {1347440,
	title = {Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population},
	journal = {Ophthalmology},
	volume = {125},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {1526-1536},
	abstract = {PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9{\textpm}12.3-82.1{\textpm}4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8{\textpm}21.4 μm in the Rotterdam Study I to 104.7{\textpm}12.5 μm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (β\&nbsp;= -0.38 μm/year; 95\% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (β = -0.36 μm/mmHg; 95\% CI, -0.56 to -0.15), visual impairment (β\&nbsp;= -5.50 μm; 95\% CI, -9.37 to -1.64), and history of systemic hypertension (β\&nbsp;= -0.54 μm; 95\% CI, -1.01 to -0.07) and stroke (β\&nbsp;= -1.94 μm; 95\% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (β\&nbsp;= -3.11 μm; 95\% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (β = 1.39 μm/diopter; 95\% CI, 1.19-1.59) and smoking (β\&nbsp;= 1.53 μm; 95\% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.03.026},
	author = {Mauschitz, Matthias M and Bonnemaijer, Pieter W M and Diers, Kersten and Rauscher, Franziska G and Tobias Elze and Engel, Christoph and Loeffler, Markus and Colijn, Johanna Maria and Ikram, M Arfan and Vingerling, Johannes R and Williams, Katie M and Hammond, Christopher J and Creuzot-Garcher, Catherine and Bron, Alain M and Silva, Rufino and Nunes, Sandrina and Delcourt, C{\'e}cile and Cougnard-Gr{\'e}goire, Audrey and Holz, Frank G and Klaver, Caroline C W and Breteler, Monique M B and Finger, Robert P and European Eye Epidemiology (E3) Consortium}
}
@article {541281,
	title = {Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries.},
	journal = {Neuron},
	volume = {87},
	number = {5},
	year = {2015},
	month = {2015 Sep 2},
	pages = {989-98},
	abstract = {The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2015.07.011},
	author = {Mayer, Christian and Jaglin, Xavier H and Cobbs, Lucy V and Bandler, Rachel C and Streicher, Carmen and Cepko, Constance L and Hippenmeyer, Simon and Fishell, Gord}
}
@article {1466901,
	title = {The impact of artificial intelligence in the diagnosis and management of glaucoma},
	journal = {Eye (Lond)},
	volume = {34},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {1-11},
	abstract = {Deep learning (DL) is a subset of artificial intelligence (AI), which uses multilayer neural networks modelled after the mammalian visual cortex capable of synthesizing images in ways that will transform the field of glaucoma. Autonomous DL algorithms are capable of maximizing information embedded in digital fundus photographs and ocular coherence tomographs to outperform ophthalmologists in disease detection. Other unsupervised algorithms such as principal component analysis (axis learning) and archetypal analysis (corner learning) facilitate visual field interpretation and show great promise to detect functional glaucoma progression and differentiate it from non-glaucomatous changes when compared with conventional software packages. Forecasting tools such as the Kalman filter may revolutionize glaucoma management by accounting for a host of factors to set target intraocular pressure goals that preserve vision. Activation maps generated from DL algorithms that process glaucoma data have the potential to efficiently direct our attention to critical data elements embedded in high throughput data and enhance our understanding of the glaucomatous process. It is hoped that AI will realize more accurate assessment of the copious data encountered in glaucoma management, improving our understanding of the disease, preserving vision, and serving to enhance the deep bonds that patients develop with their treating physicians.},
	issn = {1476-5454},
	doi = {10.1038/s41433-019-0577-x},
	author = {Mayro, Eileen L and Wang, Mengyu and Tobias Elze and Pasquale, Louis R}
}
@article {1470992,
	title = {A Questionnaire Assessing What Teachers of the Visually Impaired Know About Cortical/Cerebral Vision Impairment},
	journal = {Semin Pediatr Neurol},
	volume = {31},
	year = {2019},
	month = {2019 Oct},
	pages = {41-47},
	abstract = {Cortical/cerebral visual impairment (CVI) is now the main cause of visual impairment in developed countries, yet it remains poorly understood. Four hundred and ninteen teachers of the visually impaired (TVIs) from across the United States responded to a questionnaire targeted at evaluating the preparedness of TVIs to serve their students with CVI. The TVIs were asked about their background knowledge, their abilities to assess a student with CVI, and their abilities to apply what they know to best help their students. The primary finding was that there is a perceived unmet need for TVIs to receive formal training in CVI during their certification. The results of this survey provide a foundation for future research on CVI knowledge and education among TVIs.},
	issn = {1558-0776},
	doi = {10.1016/j.spen.2019.05.007},
	author = {Mazel, Ellen C and Bailin, Emma S and Tietjen, Matthew W and Palmer, Peggy A}
}
@article {1661595,
	title = {Astrocyte heterogeneity within white matter tracts and a unique subpopulation of optic nerve head astrocytes},
	journal = {iScience},
	volume = {25},
	number = {12},
	year = {2022},
	month = {2022 Dec 22},
	pages = {105568},
	abstract = {Much of what we know about astrocyte form and function is derived from the study of gray matter protoplasmic astrocytes, whereas white matter fibrous astrocytes remain relatively unexplored. Here, we used the ribotag approach to isolate ribosome-associated mRNA and investigated the transcriptome of uninjured fibrous astrocytes from three regions: unmyelinated optic nerve head, myelinated optic nerve proper, and corpus callosum. Astrocytes from each region were transcriptionally distinct and we identified region-specific astrocyte genes and pathways. Energy metabolism, particularly oxidative phosphorylation and mitochondrial protein translation emerged as key differentiators of astrocyte populations. Optic nerve astrocytes expressed higher levels of neuroinflammatory pathways than corpus callosum astrocytes and we further identified CARTPT as a new marker of optic nerve head astrocytes. These previously uncharacterized transcriptional profiles of white matter astrocyte types reveal their functional diversity and a greater heterogeneity than previously appreciated.},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2022.105568},
	author = {Mazumder, Arpan G and Jul{\'e}, Am{\'e}lie M and Cullen, Paul F and Sun, Daniel}
}
@article {1761816,
	title = {Astrocytes of the optic nerve exhibit a region-specific and temporally distinct response to elevated intraocular pressure},
	journal = {Mol Neurodegener},
	volume = {18},
	number = {1},
	year = {2023},
	month = {2023 Sep 27},
	pages = {68},
	abstract = {BACKGROUND: The optic nerve is an important tissue in glaucoma and the unmyelinated nerve head region remains an important site of many early neurodegenerative changes. In both humans and mice, astrocytes constitute the major glial cell type in the region, and in glaucoma they become reactive, influencing the optic nerve head (ONH) microenvironment and disease outcome. Despite recognizing their importance in the progression of the disease, the reactive response of optic nerve head astrocytes remains poorly understood. METHODS: To determine the global reactive response of ONH astrocytes in glaucoma we studied their transcriptional response to an elevation in IOP induced by the microbead occlusion model. To specifically isolate astrocyte mRNA in vivo from complex tissues, we used the ribotag method to genetically tag ribosomes in astrocytes, restricting analysis to astrocytes and enabling purification of astrocyte-associated mRNA throughout the entire cell, including the fine processes, for bulk RNA-sequencing. We also assessed the response of astrocytes in the more distal myelinated optic nerve proper (ONP) as glaucomatous changes manifest differently between the two regions. RESULTS: Astrocytes of the optic nerve exhibited a region-specific and temporally distinct response. Surprisingly, ONH astrocytes showed very few early transcriptional changes and ONP astrocytes demonstrated substantially larger changes over the course of the experimental period. Energy metabolism, particularly oxidative phosphorylation and mitochondrial protein translation emerged as highly upregulated processes in both ONH and ONP astrocytes, with the former showing additional upregulation in antioxidative capacity and proteolysis. Interestingly, optic nerve astrocytes demonstrated a limited neuroinflammatory response, even when challenged with a more severe elevation in IOP. Lastly, there were a greater number of downregulated processes in both astrocyte populations compared to upregulated processes. CONCLUSION: Our findings demonstrate an essential role for energy metabolism in the response of optic nerve astrocytes to elevated IOP, and contrary to expectations, neuroinflammation had a limited overall role. The transcriptional response profile is supportive of the notion that optic nerve astrocytes have a beneficial role in glaucoma. These previously uncharacterized transcriptional response of optic nerve astrocytes to injury reveal their functional diversity and a greater heterogeneity than previously appreciated.},
	issn = {1750-1326},
	doi = {10.1186/s13024-023-00658-9},
	author = {Mazumder, Arpan G and Jul{\'e}, Am{\'e}lie M and Sun, Daniel}
}
@article {1598033,
	title = {Targeting Future Pandemics, a Case for De Novo Purine Synthesis and Basic Research},
	journal = {Front Immunol},
	volume = {12},
	year = {2021},
	month = {2021},
	pages = {694300},
	abstract = {We are currently experiencing a deadly novel viral pandemic with no efficacious, readily available anti-viral therapies to SARS-CoV-2. Viruses will hijack host cellular machinery, including metabolic processes. Here, I provide theory and evidence for targeting the host de novo purine synthetic pathway for broad spectrum anti-viral drug development as well as the pursuit of basic science to mitigate the risks of future novel viral outbreaks.},
	issn = {1664-3224},
	doi = {10.3389/fimmu.2021.694300},
	author = {Mazzarino, Randall C}
}
@article {705096,
	title = {Hordeolum: Acute abscess within an eyelid sebaceous gland.},
	journal = {Cleve Clin J Med},
	volume = {83},
	number = {5},
	year = {2016},
	month = {2016 May},
	pages = {332-4},
	issn = {1939-2869},
	doi = {10.3949/ccjm.83a.15012},
	author = {McAlinden, Colm and Gonz{\'a}lez-Andrades, Miguel and Kiadaresi, Eirini}
}
@article {468981,
	title = {Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {3820-6},
	abstract = {PURPOSE: Amino-amide or amino-ester local anesthetics, which are currently used for topical ocular anesthesia, are short acting and may delay corneal healing with long-term use. In contrast, site 1 sodium channel blockers (S1SCBs) are potent local anesthetics with minimal adverse tissue reaction. In this study, we examined topical local anesthesia with two S1SCBs, tetrodotoxin (TTX) or saxitoxin (STX) individually or in combination with α2-adrenergic receptor agonists (dexmedetomidine or clonidine), and compared them with the amino-ester ocular anesthetic proparacaine. The effect of test solutions on corneal healing was also studied. METHODS: Solutions of TTX {\textpm} dexmedetomidine, TTX {\textpm} clonidine, STX {\textpm} dexmedetomidine, dexmedetomidine, or proparacaine were applied to the rat cornea. Tactile sensitivity was measured by recording the blink response to probing of the cornea with a Cochet-Bonnet esthesiometer. The duration of corneal anesthesia was calculated. Cytotoxicity from anesthetic solutions was measured in vitro. The effect on corneal healing was measured in vivo after corneal debridement followed by repeated drug administration. RESULTS: Addition of dexmedetomidine to TTX or STX significantly prolonged corneal anesthesia beyond that of either drug alone, whereas clonidine did not. Tetrodotoxin or STX coadministered with dexmedetomidine resulted in two to three times longer corneal anesthesia than did proparacaine. S1SCB-dexmedetomidine formulations were not cytotoxic. Corneal healing was not delayed significantly by any of the test solutions. CONCLUSIONS: Coadministration of S1SCBs with dexmedetomidine provided prolonged corneal anesthesia without delaying corneal wound healing. Such formulations may be useful for the management of acute surgical and nonsurgical corneal pain.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-16591},
	author = {McAlvin, James Brian and Zhan, Changyou and Dohlman, Jenny C and Kolovou, Paraskevi E and Salvador-Culla, Borja and Kohane, Daniel S}
}
@article {1504068,
	title = {The O-GlcNAc modification promotes terminal differentiation of human corneal epithelial cells},
	journal = {Glycobiology},
	volume = {30},
	number = {11},
	year = {2020},
	month = {2020 Oct 21},
	pages = {872-880},
	abstract = {Dynamic modification of nuclear and cytoplasmic proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) plays an important role in orchestrating the transcriptional activity of eukaryotic cells. Here, we report that the O-GlcNAc modification contributes to maintaining ocular surface epithelial homeostasis by promoting mucin biosynthesis and barrier function. We found that induction of human corneal epithelial cell differentiation stimulated the global transfer of O-GlcNAc to both nuclear and cytosolic proteins. Inflammatory conditions, on the other hand, were associated with a reduction in the expression of O-GlcNAc transferase at the ocular surface epithelia. Loss- and gain-of-function studies using small interfering RNA targeting O-GlcNAc transferase, or Thiamet G, a selective inhibitor of O-GlcNAc hydrolase, respectively, revealed that the presence of O-GlcNAc was necessary to promote glycocalyx barrier function. Moreover, we found that Thiamet G triggered a correlative increase in both surface expression of MUC16 and apical epithelial cell area while reducing paracellular permeability. Collectively, these results identify intracellular protein O-glycosylation as a novel pathway responsible for promoting the terminal differentiation of human corneal epithelial cells.},
	issn = {1460-2423},
	doi = {10.1093/glycob/cwaa033},
	author = {McColgan, Nicole M and Feeley, Marissa N and Woodward, Ashley M and Guindolet, Damien and Arg{\"u}eso, Pablo}
}
@article {1645486,
	title = {Bilateral enlargement of all extraocular muscles: a presenting ophthalmic sign of hematologic malignancy},
	journal = {Orbit},
	volume = {43},
	number = {1},
	year = {2024},
	month = {2024 Feb},
	pages = {160-163},
	abstract = {Hematologic malignancies such as leukemia and lymphoma can frequently present in the orbit; however, involvement of the extraocular muscles is rare. The authors report two cases of systemic hematologic malignancy presenting with bilateral extraocular muscle enlargement and associated compressive optic neuropathy (CON). Both patients experienced clinical and radiographic improvement of ocular and systemic manifestations of disease with prompt initiation of targeted chemotherapy. These cases highlight the importance of including hematologic malignancy in the differential diagnosis of atypical bilateral extraocular muscle enlargement.},
	keywords = {Eye, Hematologic Neoplasms, Humans, Oculomotor Muscles, Optic Nerve Diseases, Orbit},
	issn = {1744-5108},
	doi = {10.1080/01676830.2022.2090014},
	author = {McCoskey, Makayla and Reshef, Edith R and Wolkow, Natalie and Yoon, Michael K}
}
@article {1603850,
	title = {Eccrine poroma of the eyelid},
	journal = {Orbit},
	year = {2021},
	month = {2021 Jul 14},
	pages = {1},
	abstract = {Clinical and histopathologic case of an eyelid eccrine poroma, a benign adnexal neoplasm rarely found on the periorbital skin.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2021.1939732},
	author = {McCoskey, Makayla and Neerukonda, Vamsee K and Hatton, Mark P and Wolkow, Natalie}
}
@article {1318870,
	title = {Short Tandem Repeat (STR) Profiles of Commonly Used Human Ocular Surface Cell Lines},
	journal = {Curr Eye Res},
	volume = {43},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {1097-1101},
	abstract = {PURPOSE: The purpose of this study is to establish the short tandem repeat (STR) profiles of several human cell lines commonly used in ocular surface research. MATERIALS AND METHODS: Independently DNA was extracted from multiple passages of three human corneal epithelial cell lines, two human conjunctival epithelial cell lines and one meibomian gland cell line, from different laboratories actively involved in ocular surface research. The samples were then subjected to STR analysis on a fee-for-service basis in an academic setting and the data compared against that in available databases. RESULTS: The STR profiles for the human corneal epithelial cells were different among the three cell lines studied and for each line the profiles were identical across the samples provided by three laboratories. Profiles for the human conjunctival epithelial cells were different among the two cell lines studied. Profiles for the meibomian gland cell line were identical across the samples provided by three laboratories. No samples were contaminated by elements of other cell lines such as HeLa. CONCLUSIONS: This comprehensive study provides verification of STR profiles for commonly used human ocular surface cell lines that can now be used as a reference by others in the field to authenticate the cell lines in use in their own laboratories.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2018.1480043},
	author = {McDermott, Alison M and Baidouri, Hasna and Woodward, Ashley M and Kam, Wendy R and Liu, Yang and Chen, Xiaomin and Ziemanski, Jillian F and Vistisen, Kerry and Hazlett, Linda D and Nichols, Kelly K and Arg{\"u}eso, Pablo and Sullivan, David A}
}
@article {369036,
	title = {Control of intractable pruritus in a patient with cutaneous T-cell lymphoma using a continuous subcutaneous infusion of lidocaine.},
	journal = {J Pain Symptom Manage},
	volume = {49},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {e1-3},
	issn = {1873-6513},
	doi = {10.1016/j.jpainsymman.2014.12.005},
	author = {McDonald, Julie Clare and Spruyt, Odette and Alhatem, Albert}
}
@article {1814396,
	title = {Cranial nerve involvement, visual complications and headache syndromes in Lyme disease},
	journal = {Curr Opin Ophthalmol},
	volume = {35},
	number = {3},
	year = {2024},
	month = {2024 May 01},
	pages = {265-271},
	abstract = {PURPOSE OF REVIEW: To provide a summary of the visual manifestations and cranial neuropathies seen in Lyme disease. RECENT FINDINGS: Lyme facial palsy remains the most common manifestation of Lyme neuroborreliosis. Recent investigations show likely evidence of vagal involvement in Lyme disease. SUMMARY: The literature on Lyme neuroborreliosis continues to evolve. Lyme disease can affect nearly any cranial nerve in addition to causing various headache syndromes. The most common manifestation is Lyme disease facial palsy, occurring in up to 5-10\% of patients with documented Lyme disease. Headache syndromes are common in the context of facial palsy but can occur in isolation, and more specific headache syndromes including trigeminal and geniculate neuralgias can occur rarely. Signs and symptoms indicative of vestibulocochlear nerve involvement are relatively common, although it could be that these represent other vestibular involvement rather than a specific cranial neuropathy. Optic neuritis is a controversial entity within Lyme disease and is likely overdiagnosed, but convincing cases do exist. Physicians who see any cranial neuropathy, including optic neuritis, in an endemic area can consider Lyme disease as a possible cause.},
	keywords = {Cranial Nerve Diseases, Cranial Nerves, Facial Paralysis, Headache Disorders, Humans, Lyme Disease, Lyme Neuroborreliosis, Optic Neuritis},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000001031},
	author = {McEntire, Caleb R S and Chwalisz, Bart K}
}
@article {1363154,
	title = {Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells},
	journal = {PLoS One},
	volume = {8},
	number = {9},
	year = {2013},
	month = {2013},
	pages = {e74010},
	abstract = {The conjunctiva is a moist mucosal membrane that is constantly exposed to an array of potential pathogens and triggers of inflammation. The NACHT, leucine rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) is a Nod-like receptor that can sense pathogens or other triggers, and is highly expressed in wet mucosal membranes. NLRP3 is a member of the multi-protein complex termed the NLRP3 inflammasome that activates the caspase 1 pathway, inducing the secretion of biologically active IL-1β, a major initiator and promoter of inflammation. The purpose of this study was to: (1) determine whether NLRP3 is expressed in the conjunctiva and (2) determine whether goblet cells specifically contribute to innate mediated inflammation via secretion of IL-1β. We report that the receptors known to be involved in the priming and activation of the NLRP3 inflammasome, the purinergic receptors P2X4 and P2X7 and the bacterial Toll-like receptor 2 are present and functional in conjunctival goblet cells. Toxin-containing Staphylococcus aureus (S. aureus), which activates the NLRP3 inflammasome, increased the expression of the inflammasome proteins NLRP3, ASC and pro- and mature caspase 1 in conjunctival goblet cells. The biologically active form of IL-1β was detected in goblet cell culture supernatants in response to S. aureus, which was reduced when the cells were treated with the caspase 1 inhibitor Z-YVAD. We conclude that the NLRP3 inflammasome components are present in conjunctival goblet cells. The NRLP3 inflammasome appears to be activated in conjunctival goblet cells by toxin-containing S. aureus via the caspase 1 pathway to secrete mature IL1-β. Thus goblet cells contribute to the innate immune response in the conjunctiva by activation of the NLRP3 inflammasome.},
	keywords = {Adenosine Triphosphate, Animals, Apoptosis, Carrier Proteins, Caspase 1, Conjunctiva, Cytoskeletal Proteins, Enzyme Activation, Goblet Cells, Humans, Inflammasomes, Interleukin-1beta, Male, NLR Family, Pyrin Domain-Containing 3 Protein, Rats, Receptors, Cytoplasmic and Nuclear, Receptors, Purinergic P2X4, Receptors, Purinergic P2X7, Staphylococcal Infections, Staphylococcus aureus, Toll-Like Receptor 2},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0074010},
	author = {McGilligan, Victoria E and Gregory-Ksander, Meredith S and Li, Dayu and Moore, Jonathan E and Hodges, Robin R and Gilmore, Michael S and Moore, Tara C B and Dartt, Darlene A.}
}
@article {959446,
	title = {Clinical Reasoning: A 64-year-old man with visual distortions.},
	journal = {Neurology},
	volume = {87},
	number = {21},
	year = {2016},
	month = {2016 Nov 22},
	pages = {e252-e256},
	issn = {1526-632X},
	doi = {10.1212/WNL.0000000000003357},
	author = {McGrath, Emer R and Batra, Ayush and Lam, Alice D and Rizzo, Joseph F and Cole, Andrew J}
}
@article {1445336,
	title = {Computational modeling of retinal hypoxia and photoreceptor degeneration in patients with age-related macular degeneration},
	journal = {PLoS One},
	volume = {14},
	number = {6},
	year = {2019},
	month = {2019},
	pages = {e0216215},
	abstract = {Although drusen have long been acknowledged as a primary hallmark of dry age-related macular degeneration (AMD) their role in the disease remains unclear. We hypothesize that drusen accumulation increases the barrier to metabolite transport ultimately resulting in photoreceptor cell death. To investigate this hypothesis, a computational model was developed to evaluate steady-state oxygen distribution in the retina. Optical coherence tomography images from fifteen AMD patients and six control subjects were segmented and translated into 3D in silico representations of retinal morphology. A finite element model was then used to determine the steady-state oxygen distribution throughout the retina for both generic and patient-specific retinal morphology. Oxygen levels were compared to the change in retinal thickness at a later time point to observe possible correlations. The generic finite element model of oxygen concentration in the retina agreed closely with both experimental measurements from literature and clinical observations, including the minimal pathological drusen size identified by AREDS (64 μm). Modeling oxygen distribution in the outer retina of AMD patients showed a substantially stronger correlation between hypoxia and future retinal thinning (Pearson correlation coefficient, r = 0.2162) than between drusen height and retinal thinning (r = 0.0303) indicating the potential value of this physiology-based approach. This study presents proof-of-concept for the potential utility of finite element modeling in evaluating retinal health and also suggests a potential link between transport and AMD pathogenesis. This strategy may prove useful as a prognostic tool for predicting the clinical risk of AMD progression.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0216215},
	author = {McHugh, Kevin J and Li, Dian and Wang, Jay C and Kwark, Leon and Loo, Jessica and Macha, Venkata and Farsiu, Sina and Kim, Leo A and Saint-Geniez, Magali}
}
@article {1364516,
	title = {Impact of simulated central scotomas on visual search in natural scenes},
	journal = {Optom Vis Sci},
	volume = {89},
	number = {9},
	year = {2012},
	month = {2012 Sep},
	pages = {1385-94},
	abstract = {PURPOSE: In performing search tasks, the visual system encodes information across the visual field at a resolution inversely related to eccentricity and deploys saccades to place visually interesting targets upon the fovea, where resolution is highest. The serial process of fixation, punctuated by saccadic eye movements, continues until the desired target has been located. Loss of central vision restricts the ability to resolve the high spatial information of a target, interfering with this visual search process. We investigate oculomotor adaptations to central visual field loss with gaze-contingent artificial scotomas. METHODS: Spatial distortions were placed at random locations in 25{\textdegree} square natural scenes. Gaze-contingent artificial central scotomas were updated at the screen rate (75 Hz) based on a 250 Hz eye tracker. Eight subjects searched the natural scene for the spatial distortion and indicated its location using a mouse-controlled cursor. RESULTS: As the central scotoma size increased, the mean search time increased [F(3,28) = 5.27, p = 0.05], and the spatial distribution of gaze points during fixation increased significantly along the x [F(3,28) = 6.33, p = 0.002] and y [F(3,28) = 3.32, p = 0.034] axes. Oculomotor patterns of fixation duration, saccade size, and saccade duration did not change significantly, regardless of scotoma size. CONCLUSIONS: There is limited automatic adaptation of the oculomotor system after simulated central vision loss.},
	keywords = {Adaptation, Ocular, Adult, Follow-Up Studies, Humans, Memory, Pattern Recognition, Visual, Photic Stimulation, Saccades, Scotoma, Sensory Deprivation, Visual Fields, Young Adult},
	issn = {1538-9235},
	doi = {10.1097/OPX.0b013e318267a914},
	author = {McIlreavy, Lee and Fiser, Jozsef and Bex, Peter J}
}
@article {1559545,
	title = {Methods for Investigating Corneal Cell Interactions and Extracellular Vesicles In Vitro},
	journal = {Curr Protoc Cell Biol},
	volume = {89},
	number = {1},
	year = {2020},
	month = {2020 Dec},
	pages = {e114},
	abstract = {Science and medicine have become increasingly "human-centric" over the years. A growing shift away from the use of animals in basic research has led to the development of sophisticated in vitro models of various tissues utilizing human-derived cells to study physiology and disease. The human cornea has likewise been modeled in vitro using primary cells derived from corneas obtained from cadavers or post-transplantation. By utilizing a cell{\textquoteright}s intrinsic ability to maintain its tissue phenotype in a pre-designed microenvironment containing the required growth factors, physiological temperature, and humidity, tissue-engineered corneas can be grown and maintained in culture for relatively long periods of time on the scale of weeks to months. Due to its transparency and avascularity, the cornea is an optimal tissue for studies of extracellular matrix and cell-cell interactions, toxicology and permeability of drugs, and underlying mechanisms of scarring and tissue regeneration. This paper describes methods for the cultivation of corneal keratocytes, fibroblasts, epithelial, and endothelial cells for in vitro applications. We also provide detailed, step-by-step protocols for assembling and culturing 3D constructs of the corneal stroma, epithelial- and endothelial-stromal co-cultures and isolation of extracellular vesicles. {\textcopyright} 2020 Wiley Periodicals LLC. Basic Protocol 1: Isolating and culturing human corneal keratocytes and fibroblasts Basic Protocol 2: Isolating and culturing human corneal epithelial cells Basic Protocol 3: Isolating and culturing human corneal endothelial cells Basic Protocol 4: 3D corneal stromal construct assembly Basic Protocol 5: 3D corneal epithelial-stromal construct assembly Basic Protocol 6: 3D corneal endothelial-stromal construct assembly Basic Protocol 7: Isolating extracellular vesicles from corneal cell conditioned medium Support Protocol: Cryopreserving human corneal fibroblasts, corneal epithelial cells, and corneal endothelial cells.},
	issn = {1934-2616},
	doi = {10.1002/cpcb.114},
	author = {McKay, Tina B and Guo, Xiaoqing and Hutcheon, Audrey E K and Karamichos, Dimitrios and Ciolino, Joseph B}
}
@article {1528402,
	title = {Modeling the cornea in 3-dimensions: Current and future perspectives},
	journal = {Exp Eye Res},
	volume = {197},
	year = {2020},
	month = {2020 Aug},
	pages = {108127},
	abstract = {The cornea is an avascular, transparent ocular tissue that serves as a refractive and protective structure for the eye. Over 90\% of the cornea is composed of a collagenous-rich extracellular matrix within the stroma with the other 10\% composed by the corneal epithelium and endothelium layers and their corresponding supporting collagen layers (e.g., Bowman{\textquoteright}s and Descemet{\textquoteright}s membranes) at the anterior and posterior cornea, respectively. Due to its prominent role in corneal structure, tissue engineering approaches to model the human cornea in vitro have focused heavily on the cellular and functional properties of the corneal stroma. In this review, we discuss model development in the context of culture dimensionality (e.g., 2-dimensional versus 3-dimensional) and expand on the optical, biomechanical, and cellular functions promoted by the culture microenvironment. We describe current methods to model the human cornea with focus on organotypic approaches, compressed collagen, bioprinting, and self-assembled stromal models. We also expand on co-culture applications with the inclusion of relevant corneal cell types, such as epithelial, stromal keratocyte or fibroblast, endothelial, and neuronal cells. Further advancements in corneal tissue model development will markedly improve our current understanding of corneal wound healing and regeneration.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.108127},
	author = {McKay, Tina B and Hutcheon, Audrey E K and Guo, Xiaoqing and Zieske, James D and Karamichos, Dimitrios}
}
@article {1470976,
	title = {Mechanisms of Collagen Crosslinking in Diabetes and Keratoconus},
	journal = {Cells},
	volume = {8},
	number = {10},
	year = {2019},
	month = {2019 Oct 11},
	abstract = {Collagen crosslinking provides the mechanical strength required for physiological maintenance of the extracellular matrix in most tissues in the human body, including the cornea. Aging and diabetes mellitus (DM) are processes that are both associated with increased collagen crosslinking that leads to increased corneal rigidity. By contrast, keratoconus (KC) is a corneal thinning disease associated with decreased mechanical stiffness leading to ectasia of the central cornea. Studies have suggested that crosslinking mediated by reactive advanced glycation end products during DM may protect the cornea from KC development. Parallel to this hypothesis, riboflavin-mediated photoreactive corneal crosslinking has been proposed as a therapeutic option to halt the progression of corneal thinning by inducing intra- and intermolecular crosslink formation within the collagen fibrils of the stroma, leading to stabilization of the disease. Here, we review the pathobiology of DM and KC in the context of corneal structure, the epidemiology behind the inverse correlation of DM and KC development, and the chemical mechanisms of lysyl oxidase-mediated crosslinking, advanced glycation end product-mediated crosslinking, and photoreactive riboflavin-mediated corneal crosslinking. The goal of this review is to define the biological and chemical pathways important in physiological and pathological processes related to collagen crosslinking in DM and KC.},
	issn = {2073-4409},
	doi = {10.3390/cells8101239},
	author = {McKay, Tina B and Priyadarsini, Shrestha and Karamichos, Dimitrios}
}
@article {1522744,
	title = {Integrin: Basement membrane adhesion by corneal epithelial and endothelial cells},
	journal = {Exp Eye Res},
	year = {2020},
	month = {2020 Jul 23},
	pages = {108138},
	abstract = {Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells, the extracellular matrix, and gene expression in the nucleus. Changes in integrin expression in corneal epithelial cells and corneal endothelial cells impacts their adhesion to the epithelial basement membrane (EpBM) and Descemet{\textquoteright}s membrane, respectively. Integrins also play roles in assembly of basement membranes by both activating TGFβ1 and other growth factors. Over the past two decades, this knowledge has been translated into methods to grow corneal epithelial and endothelial cells in vitro for transplantation in the clinic thereby transforming clinical practice and quality of life for patients. Current knowledge on the expression and function of the integrins that mediate adhesion to the basement membrane expressed by corneal epithelial and endothelial cells in health and disease is summarized. This is the first review to discuss similarities and differences in the integrins expressed by both cell types.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.108138},
	author = {McKay, Tina B and Schl{\"o}tzer-Schrehardt, Ursula and Pal-Ghosh, Sonali and Stepp, Mary Ann}
}
@article {1483624,
	title = {Comparison of Modified Posterior Sub-Tenon{\textquoteright}s vs. Trans-Septal Triamcinolone Injection for Non-infectious Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Jan 04},
	pages = {1-8},
	abstract = {: To compare the safety and efficacy of trans-septal vs. modified posterior sub-Tenon{\textquoteright}s (PST) corticosteroid injections for noninfectious uveitis.: Retrospective comparison of periocular triamcinolone injection by modified PST (n = 36) vs. traditional trans-septal (n = 79) techniques. Safety and efficacy outcomes were analyzed with regression models.: There was no significant difference in visual acuity improvement between the groups at 6 months. There were higher rates of vitritis resolution in the modified PST group but this was not statistically significant (85.7\% vs 62.9\%, = .07). Intraocular pressure (IOP) elevation rate trended higher with the modified PST injection (21.9\% vs 9.0\%, = .06), with no instances of glaucoma surgery in either group. Two modified PST injection patients with refractory IOP rises had IOP normalization after corticosteroid depot removal. One year cataract surgery rates were similar.: Modified PST injection offers clinical efficacy but with possibly higher IOP response rate which could be managed with corticosteroid removal.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2019.1698748},
	author = {McKay, K Matthew and Borkar, Durga S and Sevgi, Duriye Damla and Susarla, Gayatri and Papaliodis, George N and Sobrin, Lucia}
}
@article {1478332,
	title = {Biology of corneal fibrosis: soluble mediators, integrins, and extracellular vesicles},
	journal = {Eye (Lond)},
	volume = {34},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {271-278},
	abstract = {Corneal fibrosis develops in response to injury, infection, postsurgical complications, or underlying systemic disease that disrupts the homeostasis of the tissue leading to irregular extracellular matrix deposition within the stroma. The mechanisms that regulate corneal scarring are focused heavily on the canonical transforming growth factor-β pathway and relevant activators, and their role in promoting myofibroblast differentiation. In this paper, we discuss the biochemical pathways involved in corneal fibrosis in the context of different injury models-epithelial debridement, superficial keratectomy, and penetrating incision. We elaborate on the interplay of the major pro-fibrotic factors involved in corneal scar development (e.g., transforming growth factor-β1, thrombospondin-1, and ανβ6), and explore a novel role for extracellular vesicles secreted by the wounded epithelium and the importance of the basement membrane.},
	issn = {1476-5454},
	doi = {10.1038/s41433-019-0736-0},
	author = {McKay, Tina B and Hutcheon, Audrey E K and Zieske, James D}
}
@article {1517185,
	title = {Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Jun 10},
	pages = {9426},
	abstract = {Keratoconus (KC) is classically considered a non-inflammatory condition caused by central corneal thinning that leads to astigmatism and reduced visual acuity. Previous studies have identified increased systemic levels of pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9, suggesting that KC may have an inflammatory component in at least a subset of patients. In this study, we evaluated the levels of different immunoglobulins (light and heavy chains) based on Ig α, Ig λ, Ig κ, Ig {\textmu}, and Ig heavy chain subunits in non-KC tears (n = 7 control individuals) and KC tears (n = 7 KC patients) using tandem-liquid chromatography mass spectrometry. The most abundant Ig heavy chains detected in both control individuals and KC patients were Ig α-1 and Ig α-2 likely correlating to the higher IgA levels reported in human tears. We identified significant differences in immunoglobulin κ-chain V-II levels in KC patients compared to control individuals with no significant difference in Ig κ/Ig λ ratios or heavy chain levels. Our study supports previous findings suggesting that KC possesses a systemic component that may contribute to the KC pathology. Further studies are required to define causality and establish a role for systemic immune system-dependent factors and pro-inflammatory processes in KC development or progression.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-66442-7},
	author = {McKay, Tina B and Serjersen, Henrik and Hjortdal, Jesper and Zieske, James D and Karamichos, Dimitrios}
}
@article {1478339,
	title = {Corneal Epithelial-Stromal Fibroblast Constructs to Study Cell-Cell Communication in Vitro},
	journal = {Bioengineering (Basel)},
	volume = {6},
	number = {4},
	year = {2019},
	month = {2019 Dec 04},
	abstract = {Cell-cell communication plays a fundamental role in mediating corneal wound healing following injury or infection. Depending on the severity of the wound, regeneration of the cornea and the propensity for scar development are influenced by the acute resolution of the pro-fibrotic response mediated by closure of the wound via cellular and tissue contraction. Damage of the corneal epithelium, basement membrane, and anterior stroma following a superficial keratectomy is known to lead to significant provisional matrix deposition, including secretion of fibronectin and thrombospondin-1, as well as development of a corneal scar. In addition, corneal wounding has previously been shown to promote release of extracellular vesicles from the corneal epithelium, which, in addition to soluble factors, may play a role in promoting tissue regeneration. In this study, we report the development and characterization of a co-culture system of human corneal epithelial cells and corneal stromal fibroblasts cultured for 4 weeks to allow extracellular matrix deposition and tissue maturation. The secretion of provisional matrix components, as well as small and large extracellular vesicles, was apparent within the constructs, suggesting cell-cell communication between epithelial and stromal cell populations. Laminin-1β was highly expressed by the corneal epithelial layer with the presence of notable patches of basement membrane identified by transmission electron microscopy. Interestingly, we identified expression of collagen type III, fibronectin, and thrombospondin-1 along the epithelial-stromal interface similar to observations seen in vivo following a keratectomy, as well as expression of the myofibroblast marker, α-smooth muscle actin, within the stroma. Our results suggest that this corneal epithelial-stromal model may be useful in the study of the biochemical phenomena that occur during corneal wound healing.},
	issn = {2306-5354},
	doi = {10.3390/bioengineering6040110},
	author = {McKay, Tina B and Karamichos, Dimitrios and Hutcheon, Audrey E K and Guo, Xiaoqing and Zieske, James D}
}
@article {1603880,
	title = {Assessing the Uniformity of Uveitis Clinical Concepts and Associated ICD-10 Codes Across Health Care Systems Sharing the Same Electronic Health Records System},
	journal = {JAMA Ophthalmol},
	year = {2021},
	month = {2021 Jul 01},
	abstract = {Importance: Big data studies may allow for the aggregation of patients with rare diseases such as uveitis to answer important clinical questions. Standardization of uveitis-related variables will be necessary, including the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes used to identify patients of interest. There are currently limited data on the uniformity of diagnosis mapping to ICD-10 codes for uveitis diagnoses among different health systems. Objective: To assess the degree of uniformity in mapping of uveitis clinical concepts to ICD-10 codes across health care systems using the same electronic health record (EHR) system. Design, Setting, and Participants: This multicenter survey study was conducted between September 14 and October 9, 2020, at 5 academic health care systems that use the Epic EHR. Researchers from the University of Washington, Harvard University, Stanford University, Yale University, and the University of California, San Francisco queried 54 uveitis-related diagnostic terms and recorded the associated ICD-10 codes. Main Outcomes and Measures: The degree of uniformity for uveitis clinical concepts and associated ICD-10 codes. Results: Fifty-four uveitis-related diagnostic terms were queried within the Epic EHR at 5 different health care systems. There was perfect agreement among all 5 centers for 52 of the 54 diagnostic terms. Two diagnostic terms had differences in ICD-10 coding: juvenile idiopathic arthritis associated chronic uveitis and intermediate uveitis. Intermediate uveitis was associated with codes H20.1x (ICD-10 description: chronic iridocyclitis) or H20.9 (ICD-10 description: unspecified iridocyclitis) in 3 centers while being associated with code H30.2x (ICD-10 description: posterior cyclitis) at the 2 remaining centers. The discrepancies appear to be related to a recent update in diagnostic mapping in the Epic EHR. Conclusions and Relevance: This study suggests that ICD-10 code mapping to uveitis diagnostic terminology appears to be highly uniform at different centers with the Epic EHR. However, temporal changes in diagnosis mapping to ICD-10 codes and a lack of 1-to-1 mapping of diagnosis to ICD-10 code add additional sources of complexity to the interpretation of big data studies in uveitis.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.2045},
	author = {McKay, K Matthew and Apostolopoulos, Nicholas and Dahrouj, Mohammad and Nguyen, Huy V and Reddy, Amit and Blazes, Marian and Lacy, Megan and Pepple, Kathryn L and Lee, Aaron Y and Lee, Cecilia S}
}
@article {1402585,
	title = {Choroidal Infiltrate of Unknown Cause},
	journal = {JAMA Ophthalmol},
	year = {2018},
	month = {2018 Dec 13},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.4488},
	author = {McKay, K Matthew and Sobrin, Lucia}
}
@article {1304387,
	title = {Brimonidine Ophthalmic Solution 0.025\% for Reduction of Ocular Redness: A Randomized Clinical Trial},
	journal = {Optom Vis Sci},
	volume = {95},
	number = {3},
	year = {2018},
	month = {2018 Mar},
	pages = {264-271},
	abstract = {SIGNIFICANCE: The α2-adrenergic receptor agonist brimonidine has been reported to induce conjunctival blanching in cataract, strabismus, laser refractive, and filtration procedures. Clinicians are often faced with red eyes with no apparent underlying pathology. Low-dose brimonidine reduced ocular redness in such subjects with efficacy maintained over 1 month and negligible rebound redness.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of brimonidine tartrate ophthalmic solution 0.025\% for the treatment of ocular redness.

METHODS: In this single-center, double-masked, phase 3 clinical trial, adult subjects with baseline redness of more than 1 unit in both eyes (0- to 4-unit scale) were randomized 2:1 to brimonidine 0.025\% or vehicle. A single dose was administered in-office (day 1); thereafter subjects instilled treatment four times a day for 4 weeks, with clinic visits on days 15, 29, and 36 (7 days post-treatment). Efficacy end points included investigator-evaluated redness 5 to 240 minutes post-instillation on day 1 (primary); investigator-evaluated change from baseline 1, 360, and 480 minutes post-instillation on day 1, and 1 and 5 minutes post-instillation on days 15 and 29; total clearance of redness, and subject-assessed redness. Safety/tolerability measures included adverse events, rebound redness, and drop comfort.

RESULTS: Sixty subjects were randomized (n = 40 brimonidine, n = 20 vehicle). Investigator-assessed redness was lower with brimonidine versus vehicle over the 5- to 240-minute post-instillation period (mean [SE], 0.62 [0.076] vs. 1.49 [0.108]; P < .0001) and at each time point within that period (P < .0001). At 1, 360, and 480 minutes post-instillation, respectively, the mean differences (95\% confidence interval) between treatments were -0.73 (-1.05 to -0.41), -0.57 (-0.84 to -0.29), and -0.39 (-0.67 to -0.10), respectively. No tachyphylaxis was evident with brimonidine on days 15 and 29, and minimal rebound redness was observed following discontinuation. Adverse events were infrequent, and brimonidine was rated as very comfortable.

CONCLUSIONS: Brimonidine 0.025\% appeared safe and effective for reduction of ocular redness, with an 8-hour duration of action, no evidence of tachyphylaxis, and negligible rebound redness.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001182},
	author = {McLaurin, Eugene and Cavet, Megan E and Gomes, Paul J and Ciolino, Joseph B}
}
@article {1817301,
	title = {Preclinical dose response study shows NR2E3 can attenuate retinal degeneration in the retinitis pigmentosa mouse model Rho},
	journal = {Gene Ther},
	year = {2024},
	month = {2024 Jan 26},
	abstract = {Retinitis pigmentosa (RP) is a heterogeneous disease and the main cause of vision loss within the group of inherited retinal diseases (IRDs). IRDs are a group of rare disorders caused by mutations in one or more of over 280 genes which ultimately result in blindness. Modifier genes play a key role in modulating disease phenotypes, and mutations in them can affect disease outcomes, rate of progression, and severity. Our previous studies have demonstrated that the nuclear hormone receptor 2 family e, member 3 (Nr2e3) gene reduced disease progression and loss of photoreceptor cell layers in RhoP23H-/- mice. This follow up, pharmacology study evaluates a longitudinal NR2E3 dose response in the clinically relevant heterozygous RhoP23H mouse. Reduced retinal degeneration and improved retinal morphology was observed 6 months following treatment evaluating three different NR2E3 doses. Histological and immunohistochemical analysis revealed regions of photoreceptor rescue in the treated retinas of RhoP23H+/- mice. Functional assessment by electroretinogram (ERG) showed attenuated photoreceptor degeneration with all doses. This study demonstrates the effectiveness of different doses of NR2E3 at reducing retinal degeneration and informs dose selection for clinical trials of RhoP23H-associated RP.},
	issn = {1476-5462},
	doi = {10.1038/s41434-024-00440-6},
	author = {McNamee, Shannon M and Chan, Natalie P and Akula, Monica and Avola, Marielle O and Whalen, Maiya and Nystuen, Kaden and Singh, Pushpendra and Upadhyay, Arun K and Deangelis, Margaret M and Haider, Neena B}
}
@article {1789206,
	title = {Short-term Detection of Fast Progressors in Glaucoma: The Fast-PACE (Progression Assessment through Clustered Evaluation) Study},
	journal = {Ophthalmology},
	year = {2023},
	month = {2023 Dec 29},
	abstract = {PURPOSE: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast-PACE (Progression Assessment through Clustered Evaluation) study.

DESIGN: Prospective cohort study.

PARTICIPANTS: 125 eyes from 65 primary open-angle glaucoma (POAG) subjects.

METHODS: Subjects underwent two sets of 5 weekly visits (clusters) separated by an average of 6 months, then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral-domain optical coherence tomography (SD OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing.

MAIN OUTCOME MEASURES: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up.

RESULTS: 19 of 125 eyes (15\%, CI: 9\%-24\%) progressed based on SAP 24-2 MD over the 6-month clustering period. 14 eyes (11\%, CI: 6\%-20\%) progressed on SAP 10-2 MD, and 16 (13\%, CI:8\%-21\%) by RNFL thickness, with 30 of 125 eyes (24\%, CI:16\%-34\%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71\% (CI: 53\%-85\%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94\% (CI: 88\% - 98\%). Of the 14 eyes considered fast progressors by SAP 24-2, 10-2 or SD OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93\% (CI: 66\% - 100\%) for identifying fast progression with a specificity of 85\% (CI: 77\% - 90\%).

CONCLUSION: Clustered testing in the Fast-PACE study detected fast-progressing glaucoma eyes over six months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may also be of value for short-term assessment of high-risk subjects.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.12.031},
	author = {Medeiros, Felipe A and Malek, Davina A and Tseng, Henry and Swaminathan, Swarup S and Boland, Michael V and Friedman, David S and Jammal, Alessandro}
}
@article {1363155,
	title = {A 50-year-old man with a long-standing, large-angle exotropia and limitation of adduction in the left eye},
	journal = {Digit J Ophthalmol},
	volume = {19},
	number = {4},
	year = {2013},
	month = {2013},
	pages = {64-7},
	keywords = {Cysts, Diagnosis, Differential, Exotropia, Humans, Male, Middle Aged, Ocular Motility Disorders, Oculomotor Muscles, Orbital Diseases},
	issn = {1542-8958},
	doi = {10.5693/djo.03.2013.09.004},
	author = {Mehendale, Reshma A and Stemmer-Rachamimov, Anat O and Dagi, Linda R}
}
@article {1483621,
	title = {The L V Prasad Eye Institute: A comprehensive case study of excellent and equitable eye care},
	journal = {Healthc (Amst)},
	year = {2020},
	month = {2020 Jan 13},
	pages = {100408},
	abstract = {Global healthcare delivery systems are facing ever-increasing challenges on multiple fronts. The need to study and define successful models of care delivery systems has become increasingly important. The L V Prasad Eye Institute (LVPEI) has a distinctive eye care delivery system offering rich lessons at many operational levels. The system has been developed on the basis of LVPEI{\textquoteright}s foundational public eye health study, and follows a complexity-driven (dependent on disease complexity) clinical care system forming a five-tier pyramidal model - at the apex is the quaternary care centre at Hyderabad, followed by increasing numbers of tertiary, secondary or community, primary, and rural eye care centres, where the revenue from paying patients covers free-care via an economic cross-subsidy. This has achieved a level of scale, efficiency, social impact, and clinical and scientific innovation rarely seen in a single health system. Building on the foundational principles of this pyramidal care with a robust economic cross-subsidy model, LVPEI has seamlessly established successful professional, academic, and educational systems that combine innovation, scientific discovery, and the development of in-house technologies focused on improving service quality and clinical decision making. In this case study, we show that all elements of the LVPEI model are practical and may be applicable to academic medical centres in diverse healthcare settings; currently, this is being tested in Liberia, West Africa.},
	issn = {2213-0772},
	doi = {10.1016/j.hjdsi.2019.100408},
	author = {Mehta, Mehul C and Narayanan, Raja and Thomas Aretz, H and Khanna, Rohit and Rao, Gullapalli N}
}
@article {382421,
	title = {Vitreous evaluation: a diagnostic challenge.},
	journal = {Ophthalmology},
	volume = {122},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {531-7},
	abstract = {PURPOSE: To categorize vitrectomy cytologic diagnoses and ancillary tests to address appropriate processing of low-volume vitreous samples. DESIGN: Retrospective case series. PARTICIPANTS: Five thousand seven hundred thirty-six vitreous samples. METHODS: Cytologic diagnoses of therapeutic and diagnostic vitrectomy samples and their processing protocols from 3 teaching institutions were reviewed. MAIN OUTCOME MEASURES: Diagnostic results were categorized as negative for malignancy, suspicious for malignancy, and positive for malignancy. All ancillary studies performed were documented, including special stains, immunohistochemistry analysis, cytokine levels, and polymerase chain reaction (PCR) analysis. RESULTS: Of the 5736 vitreous samples analyzed, 4683 (81.64\%) were from Tufts Medical Center (TMC), 955 (16.65\%) were from Boston Medical Center (BMC), and 98 (1.70\%) were from Massachusetts Eye Research and Surgery Institution (MERSI). Cases from TMC and BMC were therapeutic and diagnostic vitrectomies, and MERSI cases were diagnostic vitrectomies. Most vitrectomies showed negative results for malignancy: 99.47\% of TMC cases, 99.89\% of BMC cases, and 79.6\% of MERSI cases. These included vitreous hemorrhage and inflammatory or infectious findings. Ancillary studies performed in this category included Periodic Acid-Schiff staining for fungi, PCR analysis for toxoplasmosis, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex virus I and II, and vitreous cultures for infections (coagulase-negative Staphylococcus, Candida, Fusarium, and Propionibacterium species). Interleukin (IL) 10-to-IL-6 ratios were performed on 38.7\% of cases from MERSI. Fourteen cases from TMC were suspicious for malignancy based on cytologic evaluation. Eleven cases from TMC, 1 case from BMC, and 20 cases from MERSI showed positive results for malignancy and included B-cell lymphoma, retinoblastoma, melanoma, and metastatic adenocarcinoma. The ancillary testing included PCR for heavy chain immunoglobulin gene rearrangements, immunohistochemistry for EBV, in situ hybridization for κ and λ light chains, and cytogenetics. CONCLUSIONS: This is the largest data pool of reported cytologic diagnoses of diagnostic and therapeutic vitrectomy samples. Cytologic evaluation of therapeutic vitrectomy samples provides a valuable baseline of nonpathologic findings that assist in differentiation between malignancy, infections, and inflammatory conditions. Allocation of small-volume vitreous samples to select ancillary testing from the plethora of available diagnostic tests requires preoperative communication between surgeons and pathologists to ensure appropriate and timely treatment methods.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.09.016},
	author = {Mehta, Manisha and Rasheed, Reena A and Duker, Jay and Reichel, Elias and Feinberg, Edward and Husain, Deeba and Foster, Charles Stephen and Laver, Nora V}
}
@article {1642030,
	title = {A One-Step Electrochemical Aptasensor Based on Signal Amplification of Metallo Nanoenzyme Particles for Vascular Endothelial Growth Factor},
	journal = {Front Bioeng Biotechnol},
	volume = {10},
	year = {2022},
	month = {2022},
	pages = {850412},
	abstract = {In this study, a one-step electrochemical aptasensor was developed to detect the biomarker vascular endothelial growth factor (VEGF), an important protein in the pathogenesis of many retinal diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. The aptamer has a good affinity and can rapidly identify and capture VEGF based on its unique structure. We designed a VEGF aptasensor based on the aptamer recognition and complex metallo nanoenzyme particles as an electron exchange center and bridge between capture DNA and electrode. The aptamers maintained the hairpin structure to avoid nonspecific surface adsorption and expose the capture sequence outwards when the target was inexistent. Conversely, the aptamers opened the hairpin structure to release space to accomplish binding between VEGF and DNA, resulting in increased impedance. The performance of the electrochemical aptasensor is detected by electrochemical impedance spectroscopy (EIS). The limit of detection by EIS was as low as 8.2\&nbsp;pg\&nbsp;ml-1, and the linear range was 10\&nbsp;pg\&nbsp;ml-1-1\&nbsp;μg\&nbsp;ml-1. The electrochemical aptasensor also showed high specificity and reproducibility.},
	issn = {2296-4185},
	doi = {10.3389/fbioe.2022.850412},
	author = {Mei, ChenYang and Zhang, Yuanyuan and Pan, Luting and Dong, Bin and Chen, Xingwei and Gao, Qingyi and Xu, Hang and Xu, Wenjin and Fang, Hui and Liu, Siyu and McAlinden, Colm and Paschalis, Eleftherios I and Wang, Qinmei and Yang, Mei and Huang, Jinhai and Yu, A-Yong}
}
@article {913431,
	title = {High-Quality Draft Genome Sequence of the Multidrug-Resistant Clinical Isolate Enterococcus faecium VRE16.},
	journal = {Genome Announc},
	volume = {4},
	number = {5},
	year = {2016},
	month = {2016},
	abstract = {Specific lineages of the commensal bacterium Enterococcus faecium belonging to CC17, especially ST412, have been isolated from patients in several hospitals worldwide and harbor antibiotic resistance genes and virulence factors. Here, we report a high-quality draft genome sequence and highlight features of E.\&nbsp;faecium VRE16, a representative of this ST.},
	issn = {2169-8287},
	doi = {10.1128/genomeA.00992-16},
	author = {de Mello, Suelen Scarpa and Van Tyne, Daria and Dabul, Andrei Nicoli Gebieluca and Gilmore, Michael S and Camargo, Ilana L B C}
}
@article {1363156,
	title = {Transcriptional analysis of murine macrophages infected with different Toxoplasma strains identifies novel regulation of host signaling pathways},
	journal = {PLoS Pathog},
	volume = {9},
	number = {12},
	year = {2013},
	month = {2013},
	pages = {e1003779},
	abstract = {Most isolates of Toxoplasma from Europe and North America fall into one of three genetically distinct clonal lineages, the type I, II and III lineages. However, in South America these strains are rarely isolated and instead a great variety of other strains are found. T. gondii strains differ widely in a number of phenotypes in mice, such as virulence, persistence, oral infectivity, migratory capacity, induction of cytokine expression and modulation of host gene expression. The outcome of toxoplasmosis in patients is also variable and we hypothesize that, besides host and environmental factors, the genotype of the parasite strain plays a major role. The molecular basis for these differences in pathogenesis, especially in strains other than the clonal lineages, remains largely unexplored. Macrophages play an essential role in the early immune response against T. gondii and are also the cell type preferentially infected in vivo. To determine if non-canonical Toxoplasma strains have unique interactions with the host cell, we infected murine macrophages with 29 different Toxoplasma strains, representing global diversity, and used RNA-sequencing to determine host and parasite transcriptomes. We identified large differences between strains in the expression level of known parasite effectors and large chromosomal structural variation in some strains. We also identified novel strain-specifically regulated host pathways, including the regulation of the type I interferon response by some atypical strains. IFNβ production by infected cells was associated with parasite killing, independent of interferon gamma activation, and dependent on endosomal Toll-like receptors in macrophages and the cytoplasmic receptor retinoic acid-inducible gene 1 (RIG-I) in fibroblasts.},
	keywords = {Animals, Cells, Cultured, Female, Gene Expression Profiling, Gene Expression Regulation, HEK293 Cells, Host-Parasite Interactions, Humans, Macrophages, Mice, Mice, Inbred C57BL, Multigene Family, Signal Transduction, Toxoplasma},
	issn = {1553-7374},
	doi = {10.1371/journal.ppat.1003779},
	author = {Melo, Mariane B and Nguyen, Quynh P and Cordeiro, Cynthia and Hassan, Musa A and Yang, Ninghan and McKell, Ren{\'e}e and Rosowski, Emily E and Julien, Lindsay and Butty, Vincent and Dard{\'e}, Marie-Laure and Ajzenberg, Daniel and Fitzgerald, Katherine and Young, Lucy H and Saeij, Jeroen P J}
}
@article {1363158,
	title = {Immunohistochemical features of lacrimal gland epithelial tumors},
	journal = {Am J Ophthalmol},
	volume = {156},
	number = {6},
	year = {2013},
	month = {2013 Dec},
	pages = {1147-1158.e1},
	abstract = {PURPOSE: To investigate the immunohistochemical features of ocular adnexal pleomorphic adenoma and adenoid cystic carcinoma. DESIGN: Retrospective clinicopathologic study. METHODS: Clinical records and microscopic slides of 7 cases of each tumor type were reviewed. Immunohistochemical probes for Ki-67 and p53, and newer nuclear markers MYB for adenoid cystic carcinoma and PLAG1 for pleomorphic adenoma, were employed. RESULTS: Pleomorphic adenomas were asymptomatic, whereas adenoid cystic carcinomas were painful. No pleomorphic adenomas recurred; 4 adenoid cystic carcinomas recurred, resulting in 3 deaths. Unusual histopathologic variants for which immunohistochemistry proved useful included a myoepithelioma, an atypical pleomorphic adenoma, tubular and solid/basaloid variants of adenoid cystic carcinoma, and a morphologically heterogeneous adenoid cystic carcinoma of a Wolfring gland. For the pleomorphic adenomas, the average Ki-67 proliferation index was 3.8\%; p53 was weakly staining, with an average positivity of 18.5\%; PLAG1 was strongly positive in all cases; MYB was negative in 5 cases and weakly focally positive in 2 cases. For the adenoid cystic carcinomas, the average Ki-67 proliferation index was 29.1\%; p53 stained positively and strongly with an average of 39\%; none stained positively for PLAG1; and 6 out of 7 were MYB positive. CONCLUSIONS: Between pleomorphic adenoma and adenoid cystic carcinoma, there was no overlap in Ki-67 positivity. Positivity for p53 showed overlap in only one lesion of each type. PLAG1 and MYB positivity were highly discriminating between pleomorphic adenoma and adenoid cystic carcinoma. Immunohistochemical analysis should be investigated further for its role in the\&nbsp;evaluation of pleomorphic adenoma and adenoid cystic carcinoma.},
	keywords = {Adenoma, Pleomorphic, Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Adenoid Cystic, Child, DNA-Binding Proteins, Eye Neoplasms, Female, Humans, Immunoenzyme Techniques, Ki-67 Antigen, Lacrimal Apparatus Diseases, Male, Middle Aged, Proto-Oncogene Proteins c-myb, Retrospective Studies, Tomography, X-Ray Computed, Tumor Suppressor Protein p53},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.06.034},
	author = {Mendoza, Pia R and Jakobiec, Frederick A and Krane, Jeffrey F}
}
@article {1363157,
	title = {Bilateral nevus comedonicus of the eyelids},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {4},
	year = {2013},
	month = {2013 Jul-Aug},
	pages = {e95-8},
	abstract = {Nevus comedonicus is a rare developmental abnormality of the infundibulum of the hair follicle. It is usually unilateral and commonly presents at birth or during childhood. A rare case of late-onset, bilateral nevus comedonicus of the eyelids is reported. A 79-year-old man presented with asymptomatic but disfiguring eyelid lesions noted several months earlier. On physical examination, multiple papules resembling comedones were present bilaterally in the eyelids, canthi, temple regions, and bridge of the nose. Microscopically, there were deep invaginations of the follicular canals forming focal tunnels or pseudosinus tracts with poral openings to the surface. These variably cystic structures were lined by keratinizing and nonkeratinizing squamous epithelium, contained concentric lamellae of keratin in their lumens, and some were acutely or chronically inflamed. The diagnosis of a nevus comedonicus was made. The clinical and histopathologic characteristics, pathogenesis, differential diagnosis, and management of nevus comedonicus are briefly discussed.},
	keywords = {Aged, Diagnosis, Differential, Eyelid Neoplasms, Eyelids, Humans, Male, Nevus, Rare Diseases},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31827bdadb},
	author = {Mendoza, Pia R and Jakobiec, Frederick A and Townsend, Daniel J}
}
@article {1337038,
	title = {A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes.},
	journal = {Acta Ophthalmol},
	volume = {Sept 4},
	year = {2018},
	abstract = {PURPOSE:Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy.METHODS:A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme\&nbsp;or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts.RESULTS:Five hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05\&nbsp;{\texttimes}\&nbsp;10-9\&nbsp;. Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values\&nbsp;=\&nbsp;7.41\&nbsp;{\texttimes}\&nbsp;10-8\&nbsp;and 1.23\&nbsp;{\texttimes}\&nbsp;10-8\&nbsp;, respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p\&nbsp;=\&nbsp;0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p\&nbsp;=\&nbsp;0.429).CONCLUSION:This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.},
	author = {Meng, W. and Shah, KP and Pollack, S and Toppila, I and Hebert, HL and McCarthy, MI and Groop, L and Ahlqvist, E and Lyssenko, V and Agardh, E and Daniell, M and Kaidonis, G and Craig, JE and Mitchell, P and Liew, G and Kifley, A and Wang, J J and Christiansen, MW and Jensen, RA and Penman, A and Hancock, HA and Chen, CJ and Correa, A and Kuo, JZ and Li, X and Chen, Yi and Rotter, J I and Klein, R. and Klein, B and Wong, TY and Morris, AD and Doney, ASF and Colhoun, HM and Price, AL and Burdon, KP and Groop, PH and Sandholm, N and Grassi, MA and Sobrin, L and Palmer, CNA and Wellcome Trust Case Control Consortium 2 (WTCCC2); Surrogate markers for Micro- and Macro-vascular hard endpoints for Innovative}
}
@article {1363159,
	title = {Identification of an atypical zinc metalloproteinase, ZmpC, from an epidemic conjunctivitis-causing strain of Streptococcus pneumoniae},
	journal = {Microb Pathog},
	volume = {56},
	year = {2013},
	month = {2013 Mar},
	pages = {40-6},
	abstract = {Streptococcus pneumoniae is a pathogen associated with a range of invasive and noninvasive infections. Despite the identification of the majority of virulence factors expressed by S. pneumoniae, knowledge of the strategies used by this bacterium to trigger infections, especially those originating at wet-surfaced epithelia, remains limited. In this regard, we recently reported a mechanism used by a nonencapsulated, epidemic conjunctivitis-causing strain of S. pneumoniae (strain SP168) to gain access into ocular surface epithelial cells. Mechanistically, strain SP168 secretes a zinc metalloproteinase, encoded by a truncated zmpC gene, to cleave off the ectodomain of a vital defense component - the membrane mucin MUC16 - from the apical glycocalyx barrier of ocular surface epithelial cells and, thereby invades underlying epithelial cells. Here, we compare the truncated SP168 ZmpC to its highly conserved archetype from S. pneumoniae serotype 4 (TIGR4), which has been linked to pneumococcal virulence in previous studies. Comparative nucleotide sequence analyses revealed that the zmpC gene corresponding to strain SP168 has two stretches of DNA deleted near its 5{\textquoteright} end. A third 3 bp in-frame deletion, resulting in the elimination of an alanine residue, was found towards the middle segment of the SP168 zmpC. Closer examination of the primary structure revealed that the SP168 ZmpC lacks the canonical LPXTG motif - a signature typical of several surface proteins of gram-positive bacteria and of other pneumococcal zinc metalloproteinases. Surprisingly, in vitro assays performed using recombinant forms of ZmpC indicated that the truncated SP168 ZmpC induces more cleavage of the MUC16 ectodomain than its TIGR4 counterpart. This feature may help explain, in part, why S. pneumoniae strain SP168 is better equipped at abrogating the MUC16 glycocalyx barrier en route to causing epidemic conjunctivitis.},
	keywords = {CA-125 Antigen, Conjunctivitis, DNA, Bacterial, EPIDEMICS, Hydrolysis, Membrane Proteins, Metalloendopeptidases, Molecular Sequence Data, Pneumococcal Infections, Sequence Analysis, DNA, Sequence Deletion, Virulence Factors},
	issn = {1096-1208},
	doi = {10.1016/j.micpath.2012.11.006},
	author = {Menon, Balaraj B and Govindarajan, Bharathi}
}
@article {369086,
	title = {Suppression of Toll-like receptor-mediated innate immune responses at the ocular surface by the membrane-associated mucins MUC1 and MUC16.},
	journal = {Mucosal Immunol},
	volume = {8},
	number = {5},
	year = {2015},
	month = {2015 Sep},
	pages = {1000-8},
	abstract = {Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form a dense glycocalyx that is hypothesized to protect the cornea and conjunctiva from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16, expressed on the apical surface of the corneal epithelium, suppress Toll-like receptor (TLR)-mediated innate immune responses was tested. Using an in vitro model of corneal epithelial cells that are cultured to express MAMs, we show that reduced expression of either MUC1 or MUC16 correlates with increased message and secreted protein levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) following exposure of cells to the TLR2 and TLR5 agonists, heat-killed Listeria monocytogenes and flagellin, respectively. As mice express Muc1 (but not Muc16) in the corneal epithelium, a Muc1(-/-) mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF-α message levels were increased in the corneal epithelium of Muc1(-/-) mice, in comparison with wild-type mice, following exposure of enucleated eyes to the TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16 contribute to the maintenance of immune homeostasis at the ocular surface by limiting TLR-mediated innate immune responses.},
	issn = {1935-3456},
	doi = {10.1038/mi.2014.127},
	author = {Menon, B B and Kaiser-Marko, C and Spurr-Michaud, S and Tisdale, A S and Gipson, I K}
}
@article {1470968,
	title = {Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration},
	journal = {Nat Commun},
	volume = {10},
	number = {1},
	year = {2019},
	month = {2019 Oct 25},
	pages = {4902},
	abstract = {Genome-wide association studies (GWAS) have identified genetic variants associated with age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. However, it has been challenging to identify the cell types associated with AMD given the genetic complexity of the disease. Here we perform massively parallel single-cell RNA sequencing (scRNA-seq) of human retinas using two independent platforms, and report the first single-cell transcriptomic atlas of the human retina. Using a multi-resolution network-based analysis, we identify all major retinal cell types, and their corresponding gene expression signatures. Heterogeneity is observed within macroglia, suggesting that human retinal glia are more diverse than previously thought. Finally, GWAS-based enrichment analysis identifies glia, vascular cells, and cone photoreceptors to be associated with the risk of AMD. These data provide a detailed analysis of the human retina, and show how scRNA-seq can provide insight into cell types involved in complex, inflammatory genetic diseases.},
	issn = {2041-1723},
	doi = {10.1038/s41467-019-12780-8},
	author = {Menon, Madhvi and Mohammadi, Shahin and Davila-Velderrain, Jose and Goods, Brittany A and Cadwell, Tanina D and Xing, Yu and Stemmer-Rachamimov, Anat and Shalek, Alex K and Love, John Christopher and Kellis, Manolis and Hafler, Brian P}
}
@article {1364517,
	title = {Teaching the blind to find their way by playing video games},
	journal = {PLoS One},
	volume = {7},
	number = {9},
	year = {2012},
	month = {2012},
	pages = {e44958},
	abstract = {Computer based video games are receiving great interest as a means to learn and acquire new skills. As a novel approach to teaching navigation skills in the blind, we have developed Audio-based Environment Simulator (AbES); a virtual reality environment set within the context of a video game metaphor. Despite the fact that participants were na{\"\i}ve to the overall purpose of the software, we found that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building using audio based cues alone. This was confirmed by a series of behavioral performance tests designed to assess the transfer of acquired spatial information to a large-scale, real-world indoor navigation task. Furthermore, learning the spatial layout through a goal directed gaming strategy allowed for the mental manipulation of spatial information as evidenced by enhanced navigation performance when compared to an explicit route learning strategy. We conclude that the immersive and highly interactive nature of the software greatly engages the blind user to actively explore the virtual environment. This in turn generates an accurate sense of a large-scale three-dimensional space and facilitates the learning and transfer of navigation skills to the physical world.},
	keywords = {Adult, Blindness, Female, Humans, Learning, Male, SPATIAL behavior, User-Computer Interface, Video Games, Young Adult},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0044958},
	author = {Merabet, Lotfi B and Connors, Erin C and Halko, Mark A and S{\'a}nchez, Jaime}
}
@article {1688291,
	title = {Motion and form coherence processing in individuals with cerebral visual impairment},
	journal = {Dev Med Child Neurol},
	volume = {65},
	number = {10},
	year = {2023},
	month = {2023 Oct},
	pages = {1379-1386},
	abstract = {AIM: Using a visual psychophysical paradigm, we sought to assess motion and form coherence thresholds as indices of dorsal and ventral visual stream processing respectively, in individuals with cerebral visual impairment (CVI). We also explored potential associations between psychophysical assessments and brain lesion severity in CVI. METHOD: Twenty individuals previously diagnosed with CVI (mean age = 17 years 11 months [SD 5 years 10 months]; mean Verbal IQ = 86.42 [SD 35.85]) and 30 individuals with neurotypical development (mean age = 20 years 1 month [SD 3 years 8 months]; mean Verbal IQ = 110.05 [SD 19.34]) participated in the study. In this two-group comparison, cross-sectional study design, global motion, and form pattern coherence thresholds were assessed using a computerized, generalizable, self-administrable, and response-adaptive psychophysical paradigm called FInD (Foraging Interactive D-prime). RESULTS: Consistent with dorsal stream dysfunction, mean global motion (but not form) coherence thresholds were significantly higher in individuals with CVI compared to controls. No statistically significant association was found between coherence thresholds and lesion severity. INTERPRETATION: These results suggest that the objective assessment of motion and form coherence threshold sensitivities using this psychophysical paradigm may be useful in helping to characterize perceptual deficits and the complex clinical profile of CVI. WHAT THIS PAPER ADDS: In participants with cerebral visual impairment (CVI), motion (but not form) coherence thresholds were significantly higher compared to controls. These psychophysical results support the notion of dorsal stream dysfunction in CVI.},
	keywords = {Adolescent, Adult, Brain Diseases, Cross-Sectional Studies, Eye Movements, Humans, Motion Perception, Vision Disorders, Young Adult},
	issn = {1469-8749},
	doi = {10.1111/dmcn.15591},
	author = {Merabet, Lotfi B and Manley, Claire E and Pamir, Zahide and Bauer, Corinna M and Skerswetat, Jan and Bex, Peter J}
}
@article {1647886,
	title = {Prevalence and Characteristics of Cytomegalovirus Ocular Disease in Children: A Multi-Center Study},
	journal = {Clin Ophthalmol},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {2209-2217},
	abstract = {Purpose: The objective of this study was to identify the prevalence of CMV ocular disease in children and to identify associated risk factors for ocular involvement. Design: Retrospective multicenter, cross-sectional study. Methods: Setting: Hospitalized patients screened for CMV viremia by PCR between 2005 and 2018 at four pediatric referral centers. Participants: Seven-hundred and ninety-three children showed CMV viremia (\&gt;135 copies/mL by polymerase chain reaction; PCR). Main Outcomes and Measures: (1) Occurrence of ophthalmologic examination. (2) Presence of CMV ocular disease, defined as retinitis, vasculitis, hemorrhage, optic nerve atrophy, or anterior uveitis in the setting of CMV viremia without other identifiable causes. Results: A total of 296/793 (37\%) underwent ophthalmologic examination following CMV viremia. A total of23/296 patients (8\%) had ocular symptoms prompting evaluation while the rest had eye exams for baseline screening unrelated to CMV viremia. Of these, 13 cases (4\% of those with an eye exam) with ocular disease were identified (three congenital CMV, five severe combined immunodeficiency disorder (SCID) status post-stem cell transplantation, three hematologic malignancy status post-stem cell transplantation for two of them, one Evans syndrome status post-stem cell transplantation, and one medulloblastoma status post-bone marrow transplantation). No patients with solid organ transplantation developed CMV ocular disease in our cohort. Conclusion: CMV ocular disease was a rare occurrence in this cohort without an identifiable pattern across sub-groups. Excluding the three congenital CMV cases, nine out of ten patients with CMV ocular disease were status post-stem cell transplantation. We provide integrated screening guidelines based on the best available evidence for this rare condition.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S364741},
	author = {Mercado, Carmel L and Froines, Colin P and Gaier, Eric D and Wang, Qinyun and Indaram, Maanasa and Wan, Michael J and Shah, Ankoor S and Koo, Euna B}
}
@article {1748376,
	title = {Telemedicine Training in Ophthalmology Residency Programs},
	journal = {J Acad Ophthalmol (2017)},
	volume = {15},
	number = {2},
	year = {2023},
	month = {2023 Jul},
	pages = {e172-e174},
	issn = {2475-4757},
	doi = {10.1055/s-0043-1772789},
	author = {Meshkin, Ryan S and Aziz, Kanza and Weinert, Marguerite C and Lorch, Alice C and Armstrong, Grayson W}
}
@article {1629469,
	title = {Effectiveness of a telemedicine program for triage and diagnosis of emergent ophthalmic conditions},
	journal = {Eye (Lond)},
	volume = {37},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {325-331},
	abstract = {BACKGROUND: To study the utility of a teleophthalmology program to diagnose and triage common ophthalmic complaints presenting to an ophthalmic emergency room. METHODS: Prospective, observational study of 258 eyes of 129 patients presenting to the Massachusetts Eye and Ear Infirmary Emergency Ward (MEE EW) who completed a questionnaire to gather chief complaint (CC), history of present illness, and medical history. Anterior and posterior segment photographs were collected via iPhone 5 C camera and a Canon non-mydriatic fundus camera, respectively. Ophthalmic vital signs were collected. All information was reviewed remotely by three ophthalmologists; a diagnosis and urgency designation were recorded. The remote assessment was compared to gold standard in-person assessment. RESULTS: The 129 recruited patients collectively contributed 220 visual complaints, of which 121 (55\%) were from females with mean age 56.5 years (range 24-89). Sensitivities and specificities for telemedical triage were as follows: eye pain (n = 56; sensitivity: 0.58, CI [0.41, 0.74]; specificity: 0.91, CI [0.80, 1]), eye redness (n = 54; 0.68, CI [0.50, 0.86]; 0.93, CI [0.84, 1]), blurry vision (n = 68; 0.73, CI [0.60, 0.86]; 0.91, CI [0.80, 1]), and eyelid complaints (n = 42; 0.67, CI [0.43, 0.91]; 0.96, CI [0.89, 1]). The remote diagnostic accuracies, as stratified by CC, were eye pain (27/56; 48.21\%), eye redness: (32/54; 59.26\%), blurry vision: (30/68; 44.11\%), eyelid (24/42; 57.14\%). CONCLUSIONS: Telemedical examination of emergent ophthalmic complaints consisting of a patient questionnaire, anterior segment and fundus photos, and ophthalmic vital signs, may be useful to reliably triage eye disease based on presenting complaint.},
	keywords = {Adult, Aged, Aged, 80 and over, Eye Pain, Female, Fundus Oculi, Humans, Middle Aged, Ophthalmology, Prospective Studies, Telemedicine, Triage, Vision Disorders, Young Adult},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-01940-8},
	author = {Meshkin, Ryan S and Armstrong, Grayson W and Hall, Nathan E and Rossin, Elizabeth J and Hymowitz, Maggie B and Lorch, Alice C}
}
@article {1647876,
	title = {Remote Video Monitoring of Simultaneous Visual Field Testing},
	journal = {J Glaucoma},
	volume = {31},
	number = {7},
	year = {2022},
	month = {2022 Jul 01},
	pages = {488-493},
	abstract = {PRCIS: In this prospective interventional case series that included 474 patients, there were no significant differences in visual field (VF) parameters between fields from patients tested one-at-a-time and simultaneously, except for fixation losses. PURPOSE: To test for differences in reliability and performance parameters of patients taking VF tests while using a remote patient monitoring system to supervise 1 or 2 test sessions simultaneously. METHODS: In a prospective interventional case series, 861 eyes of 474 consecutive patients undergoing automated perimetry during a 6-month period were monitored during the test using an audio/video-enabled remote monitoring system. Two patients were simultaneously tested (simultaneous test) by a single technician if they were ready for testing at the same time. Patients were otherwise tested individually (single test). Performance and reliability parameters including false negatives, false positives, fixation losses, mean deviation, pattern standard deviation, VF index, and test duration were compared between patients undergoing simultaneous tests and single tests. Patients undergoing remotely monitored testing, for whom a prior VF could be found, had performance and reliability parameters compared with those prior tests. VFs were analyzed separately for 2 test strategies: SITA Standard 24-2 and SITA Faster 24-2C. RESULTS: No significant parameter differences were observed among SITA Standard 24-2 VFs between single and simultaneous tests, except for fixation losses (single: 16.8{\textpm}19.7\%, simultaneous: 22.5{\textpm}25.0\%, P=0.01). Similarly, there were no significant differences observed among SITA Faster 24-2C tests. Paired analyses comparing remotely monitored VFs with prior traditionally monitored VFs showed no significant differences for any parameters, except for fewer fixation losses with remote monitoring (traditional: 23.6{\textpm}27.5\%, remote 17.7{\textpm}20.8\%, P=0.003). CONCLUSIONS: Remote patient monitoring of VF testing enabled technicians to supervise testing of 2 patients simultaneously with preserved performance and reliability.},
	keywords = {Humans, Intraocular Pressure, Prospective Studies, Reproducibility of Results, Visual Field Tests, Visual Fields},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002045},
	author = {Meshkin, Ryan S and Zhao, Yan and Tobias Elze and Boland, Michael V and Friedman, David S}
}
@article {591256,
	title = {Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System.},
	journal = {J Neuropathol Exp Neurol},
	volume = {74},
	number = {11},
	year = {2015},
	month = {2015 Nov},
	pages = {1077-85},
	abstract = {The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination. A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type-specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases.},
	issn = {1554-6578},
	doi = {10.1097/NEN.0000000000000253},
	author = {Meyer Zu Horste, Gerd and Derksen, Angelika and Stassart, Ruth and Szepanowski, Fabian and Thanos, Melissa and Stettner, Mark and Boettcher, Christina and Lehmann, Helmar C and Hartung, Hans-Peter and Kieseier, Bernd C}
}
@article {1309954,
	title = {Age-Related Changes to Human Tear Composition},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {5},
	year = {2018},
	month = {2018 Apr 01},
	pages = {2024-2031},
	abstract = {Purpose: We characterize age-associated alterations in the expression of inflammatory mediators and tissue remodeling factors in human tears. Methods: A total of 75 consecutive volunteers (32 male/44 female; 19-93 years) underwent clinical assessment of ocular surface status, ocular surface disease index (OSDI) grading and tear sampling. The volunteers were categorized into three groups: young (18-40 years), middle-aged (41-60 years), and old (\&gt;60 years). Total protein profiles and chip-based protein array evaluations were conducted to investigate the expression of 60 potential candidates, including pro-/anti-inflammatory mediators and tissue remodeling factors. Appropriate validations were performed using conventional assays. Multiple comparisons for regression between potential candidates and age were performed, as well as statistical analyses among the three age groups. Nonpooled samples were used for quantifications. Results: Pearson analysis of chip-arrays identified 9 of 60 potential candidates. Specifically, IL-8, IL-6, and regulated on activation, normal T cell expressed and secreted (RANTES; P \&lt; 0.0083) protein as well as matrix metalloproteinase (MMP)-1, IL-3, and TNF-α (P \&lt; 0.05) correlated positively with aging. MIP-3β showed an opposite tendency. Western blot and ELISA analysis corroborated the array data. OSDI grading did not correlate with aging. Conclusions: Dynamic changes to tear protein profiles occur with aging. Our study identifies the expression of IL-8, IL-6, RANTES, MMP-1, and MIP-3β as increasing with age. These select inflammatory and matrix remodeling factors may be relevant to the development of novel diagnostic tools and therapeutics in the context of age-related ocular surface disease.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-23358},
	author = {Micera, Alessandra and Di Zazzo, Antonio and Esposito, Graziana and Longo, Rosa and Foulsham, William and Sacco, Roberto and Sgrulletta, Roberto and Bonini, Stefano}
}
@article {1059781,
	title = {Ocular Motor Nerve Development in the Presence and Absence of Extraocular Muscle},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {4},
	year = {2017},
	month = {2017 Apr 01},
	pages = {2388-2396},
	abstract = {Purpose: To spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs). Methods: Myf5cre mice, which in the homozygous state lack EOMs, were crossed to an IslMN:GFP reporter line to fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to E15.5 wild-type and Myf5cre/cre:IslMN:GFP whole mount embryos and dissected orbits were imaged by confocal microscopy to visualize the developing oculomotor, trochlear, and abducens nerves in the presence and absence of EOMs. E11.5 and E18.5 brainstems were serially sectioned and stained for Islet1 to determine the fate of ocular motor neurons. Results: At E11.5, all three ocular motor nerves in mutant embryos approached the orbit with a trajectory similar to that of wild-type. Subsequently, while wild-type nerves send terminal branches that contact target EOMs in a stereotypical pattern, the Myf5cre/cre ocular motor nerves failed to form terminal branches, regressed, and by E18.5 two-thirds of their corresponding motor neurons died. Comparisons between mutant and wild-type embryos revealed novel aspects of trochlear and oculomotor nerve development. Conclusions: We delineated mouse ocular motor nerve spatial and temporal development in unprecedented detail. Moreover, we found that EOMs are not necessary for initial outgrowth and guidance of ocular motor axons from the brainstem to the orbit but are required for their terminal branching and survival. These data suggest that intermediate targets in the mesenchyme provide cues necessary for appropriate targeting of ocular motor axons to the orbit, while EOM cues are responsible for terminal branching and motor neuron survival.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-21268},
	author = {Michalak, Suzanne M and Whitman, Mary C and Park, Jong G and Tischfield, Max A and Nguyen, Elaine H and Engle, Elizabeth C}
}
@article {1661849,
	title = {Subthreshold Amblyopia: Characterization of a New Cohort},
	journal = {Am J Ophthalmol},
	volume = {251},
	year = {2023},
	month = {2023 Jul},
	pages = {156-164},
	abstract = {PURPOSE: Published studies of amblyopia include only patients with visual acuity (VA) worse than 20/40 in one or both eyes. The purpose of this study is to evaluate patients diagnosed and treated as amblyopic despite not meeting traditional VA criteria for amblyopia. DESIGN: Retrospective clinical cohort study. METHODS: Setting: Institutional practice. PATIENT POPULATION: All patients diagnosed with amblyopia at Boston Children{\textquoteright}s Hospital between 2010 and 2014. INCLUSION CRITERIA: VA better than 20/40 but not correctable to 20/20 in one or both eyes; age 2 to 12 years. OBSERVATIONS: Demographics, VA, baseline characteristics. OUTCOME MEASURES: Resolution, defined as VA 20/20 in both eyes; stereopsis at the last follow-up. RESULTS: Of 2311 patients reviewed, 464 (20.1\%) had subthreshold amblyopia. A majority (61.7\%) had an amblyogenic factor, most commonly anisometropia (32.8\%). Patients were followed for a median of 3.1 years; nearly all (97.5\%) were treated. Of 318 patients who returned for follow-up, 47.8\% achieved resolution, including 55.7\% of treatment-na{\"\i}ve patients, and 62.5\% (5 of 8 patients) offered observation alone.\&nbsp;Median stereopsis improved by 0.4 log units in those who achieved resolution, with no change in those with persistent amblyopia. In the multivariate analysis, a longer length of follow-up was significantly associated with resolution of subthreshold amblyopia (odds ratio: 1.38; 95\% confidence interval: 1.22-1.57, P \&lt; .001). CONCLUSIONS: Patients with subthreshold amblyopia represent a sizeable cohort in real-world amblyopia practice. When offered treatment, half achieved 20/20 vision in both eyes with improved stereopsis as well. Further studies are needed to assess whether observation alone would result in similar outcomes.},
	keywords = {Amblyopia, Anisometropia, Child, Child, Preschool, Cohort Studies, Humans, Retrospective Studies, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.12.015},
	author = {Michalak, Suzanne M and Chinn, Ryan N and Shoshany, Talia N and Bishop, Kaila and Staffa, Steven J and Hunter, David G}
}
@article {1351169,
	title = {Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy},
	journal = {PLoS One},
	volume = {9},
	number = {1},
	year = {2014},
	month = {2014},
	pages = {e85031},
	abstract = {Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading to tissue ischemia and hypoxia, followed by sight threatening pathologic neovascularization in the second phase. Previously we found that Sirtuin1 (Sirt1), a metabolically dependent protein deacetylase, regulates vascular regeneration in a mouse model of oxygen-induced proliferative retinopathy (OIR), as neuronal depletion of Sirt1 in retina worsens retinopathy. In this study we assessed whether over-expression of Sirtuin1 in retinal neurons and vessels achieved by crossing Sirt1 over-expressing flox mice with Nestin-Cre mice or Tie2-Cre mice, respectively, may protect against retinopathy. We found that over-expression of Sirt1 in Nestin expressing retinal neurons does not impact vaso-obliteration or pathologic neovascularization in OIR, nor does it influence neuronal degeneration in OIR. Similarly, increased expression of Sirt1 in Tie2 expressing vascular endothelial cells and monocytes/macrophages does not protect retinal vessels in OIR. In addition to the genetic approaches, dietary supplement with Sirt1 activators, resveratrol or SRT1720, were fed to wild type mice with OIR. Neither treatment showed significant vaso-protective effects in retinopathy. Together these results indicate that although endogenous Sirt1 is important as a stress-induced protector in retinopathy, over-expression of Sirt1 or treatment with small molecule activators at the examined doses do not provide additional protection against retinopathy in mice. Further studies are needed to examine in depth whether increasing levels of Sirt1 may serve as a potential therapeutic approach to treat or prevent retinopathy.},
	keywords = {Animals, Crosses, Genetic, Disease Models, Animal, Endothelial Cells, Gene Expression, Heterocyclic Compounds, 4 or More Rings, Humans, Integrases, Macrophages, Mice, Neovascularization, Pathologic, Nerve Degeneration, Nestin, Neurons, Oxygen, Receptor, TIE-2, Retina, Retinal Degeneration, Sirtuin 1, Stilbenes},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0085031},
	author = {Michan, Shaday and Juan, Aimee M and Hurst, Christian G and Cui, Zhenghao and Evans, Lucy P and Hatton, Colman J and Pei, Dorothy T and Ju, Meihua and Sinclair, David A and Smith, Lois E H and Chen, Jing}
}
@article {1655719,
	title = {Visual intervention in early onset visual impairment: A review},
	journal = {Eur J Neurosci},
	volume = {57},
	number = {12},
	year = {2023},
	month = {2023 Jun},
	pages = {1998-2016},
	abstract = {Vision is a primary and motivating sense. Early visual experience derived from the external world is known to have an important impact on the development of central visual pathways, and not surprisingly, visual impairment constitutes a risk factor for overall development. In light of the role of vision in early brain development, infants and young children with visual impairment should be thus entitled to early and effective visual intervention programmes. In this review, we discuss early visual interventions in infants and young children with visual impairment, focusing on their contents and outcomes. We defined a PICO format to critically review different models with a particular focus on parent-mediated and therapist-mediated approaches. We consider protocols that involved direct manipulation or improvement of the infants{\textquoteright} visual inputs or were based on behavioural strategies and communication towards infants with visual impairment. We also provide an overview of the effectiveness of these protocols. A total of nine intervention protocols were selected for the purposes of this review. Substantial agreement regarding the importance of promoting the enrichment of infant environments, and more specifically in the context of active play that engages the whole family, has been reported in most of the studies. However, there is no clear agreement on methodological aspects, including clinical population characteristics, outcome measures, length of treatment and follow-up programmes. Further high-quality, carefully designed and adequately reported studies are needed in order to improve the clinical efficacy of these approaches to treating infants with visual impairment.},
	keywords = {Child, Child, Preschool, Humans, Infant, Vision Disorders, Vision, Ocular},
	issn = {1460-9568},
	doi = {10.1111/ejn.15841},
	author = {Micheletti, Serena and Merabet, Lotfi B and Galli, Jessica and Fazzi, Elisa}
}
@article {1782406,
	title = {Academic skills in children with cerebral palsy and specific learning disorders},
	journal = {Dev Med Child Neurol},
	year = {2023},
	month = {2023 Nov 21},
	abstract = {AIM: To investigate the prevalence and clinical manifestations of reading, writing, and mathematics disorders in children with cerebral palsy (CP). We explored how the clinical profile of these children differed from those with specific learning disorders (SLDs), taking into account several factors, particularly IQ scores, neuropsychological aspects, and the presence of a visual impairment. METHOD: A prospective cross-sectional study was conducted in 42 children with CP (mean age 9 years 8 months; SD = 2 years 2 months) and 60 children with SLDs (mean age 10 years; SD = 1 year 7 months). Clinical characteristics, neuromotor and cognitive profiles, neuropsychological aspects (speech performance, academic skills, visual attention, phonological awareness, working memory), and signs of visual impairment (visual acuity, contrast sensitivity, visual field, oculomotor functions) were assessed. A machine learning approach consisting of a random forest algorithm, where the outcome was the diagnosis and the covariates were the clinical variables collected in the sample, was used for the analyses. RESULTS: About 59\% of the children with CP had reading, writing, or mathematics disorders. Children with CP with learning disorders had a low performance IQ, normal phonological awareness, and working memory difficulties, whereas children with SLDs had normal performance IQ, impaired phonological awareness, and mild working memory difficulties. There were no differences in verbal IQ between the two groups. INTERPRETATION: Learning disorders are frequently associated with CP, with different clinical characteristics, compared with SLDs. Assessment of academic skills is mandatory in these children, even if the IQ is normal. At school age, specific interventions to promote academic skills in children with CP could be a major rehabilitative goal.},
	issn = {1469-8749},
	doi = {10.1111/dmcn.15808},
	author = {Micheletti, Serena and Galli, Jessica and Vezzoli, Marika and Scaglioni, Vera and Agostini, Stefania and Calza, Stefano and Merabet, Lotfi B and Fazzi, Elisa}
}
@article {1522717,
	title = {Evaluating Goldmann Applanation Tonometry Intraocular Pressure Measurement Agreement Between Ophthalmic Technicians and Physicians},
	journal = {Am J Ophthalmol},
	volume = {219},
	year = {2020},
	month = {2020 11},
	pages = {170-176},
	abstract = {PURPOSE: To examine IOP measurement disagreement between technicians and physicians and the impact of an educational intervention on the short and long-term disagreement in IOP measurement using Goldmann applanation tonometry. DESIGN: Prospective study designed to enhance measurement reliability. SETTING: A glaucoma clinic at a university hospital. StudyPopulation: 6 technicians and 2 physicians. INTERVENTION: An educational intervention was implemented for the technicians to improve IOP measurement agreement with physicians. MainOutcomeMeasures: Frequency of IOP measurement disagreement between physicians and technicians, defined as a difference in IOP of \&gt;2 or \&gt;3\&nbsp;mm Hg and assessed at baseline and immediately and 6\&nbsp;months postintervention. RESULTS: IOP was evaluated for a total of 529 eyes (physician measured mean IOP\&nbsp;= 16.4\&nbsp;mm Hg [SD\&nbsp;= 5.9]), 30 per technician-physician pair for each data collection period: baseline, immediately postintervention and 6\&nbsp;months postintervention. At baseline, physicians disagreed 17\% and 7\% of the time when measuring IOP using \&gt;2 and \&gt;3\&nbsp;mm Hg to define disagreement, respectively, whereas the average disagreement between technicians and physicians was 25\% and 13\%. Disagreement was greater at IOPs greater than 20\&nbsp;mm Hg. No significant changes were noted in the frequency of disagreement between technicians and physicians immediately or 6\&nbsp;months postintervention. CONCLUSIONS: Two physicians measuring the same patient in the same room disagreed by \&gt;2\&nbsp;mm Hg in 17\% of patients{\textquoteright} eyes, and this amount of disagreement was even higher when comparing physicians to certified technicians. An educational intervention did not improve agreement in IOP measurements between technicians and physicians. This highlights an important limitation of Goldmann tonometry.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.06.041},
	author = {Mihailovic, Aleksandra and Varadaraj, Varshini and Ramulu, Pradeep Y and Friedman, David S}
}
@article {959451,
	title = {Resident Compliance With the American Academy of Ophthalmology Preferred Practice Patterns for Primary Open-Angle Glaucoma Suspect.},
	journal = {J Glaucoma},
	volume = {25},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {963-967},
	abstract = {PURPOSE: To study resident compliance with the American Academy of Ophthalmology (AAO) Preferred Practice Patterns (PPPs) for primary open-angle glaucoma suspect (POAGS) in a resident ophthalmology clinic. PATIENTS AND METHODS: Two hundred charts were selected for analysis of adult patients with the International Classification of Diseases diagnosis code for POAGS during their initial visit between November 2, 2010 and May 6, 2014 at the Kresge Eye Institute resident clinic. Electronic medical records of clinic visits for POAGS patients were evaluated for documentation and compliance with 17 elements of AAO PPPs. RESULTS: The overall mean compliance was 73.8\% for all charts (n=200), 74.4\% for first-year residents (n=53), 74.5\% for second-year residents (n=38), and 73.3\% for third-year residents (n=109). Documentation rates were high (\&gt;90\%) for 9 elements, which included most elements of physical examination and history. Documentation of ocular history, central corneal thickness, gonioscopy, optic nerve head and retinal nerve fiber layer analysis, and visual field ranged from 40\% to 80\%. Documentation was lowest for patient education elements which ranged from 0\% to 10\%. Compliance was not significantly different (P\&gt;0.05) between residents or between different resident years for any element. CONCLUSIONS: Residents{\textquoteright} compliance was high for most elements of the PPPs for POAGS. We identified elements with poor compliance especially regarding patient education. Adherence to AAO PPPs can be a helpful method of assessing resident performance.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000548},
	author = {Mihlstin, Melanie and Juzych, Mark S and Kromrei, Heidi T and Hwang, Frank S and Yin, Jia}
}
@article {959456,
	title = {Patients with multiple sclerosis demonstrate reduced subbasal corneal nerve fibre density},
	journal = {Mult Scler},
	volume = {23},
	number = {14},
	year = {2017},
	month = {2017 Dec},
	pages = {1847-1853},
	abstract = {BACKGROUND: Many studies in multiple sclerosis (MS) have investigated the retina. Little, however, is known about the effect of MS on the cornea, which is innervated by the trigeminal nerve. It is the site of neural-immune interaction with local dendritic cells reacting in response to environmental stimuli. OBJECTIVE: This study aims to investigate the effect of MS on corneal nerve fibres and dendritic cells in the subbasal nerve plexus using in vivo confocal microscopy (IVCM). METHODS: We measured the corneal nerve fibre and dendritic cell density in 26 MS patients and matched healthy controls using a Heidelberg Retina Tomograph with cornea module. Disease severity was assessed with the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale, visual acuity and retinal optical coherence tomography. RESULTS: We observed significant reduction in total corneal nerve fibre density in MS patients compared to controls. Dendritic cell density was similar in both groups. Reduced total nerve fibre density was associated with worse clinical severity but not with previous clinical trigeminal symptoms, retinal neuro-axonal damage, visual acuity or disease duration. CONCLUSION: Corneal nerve fibre density is a promising new imaging marker for the assessment of disease severity in MS and should be investigated further.},
	issn = {1477-0970},
	doi = {10.1177/1352458516677590},
	author = {Mikolajczak, Janine and Zimmermann, Hanna and Kheirkhah, Ahmad and Kadas, Ella Maria and Oberwahrenbrock, Timm and Muller, Rodrigo and Ren, Aiai and Kuchling, Joseph and Dietze, Holger and Pr{\"u}ss, Harald and Paul, Friedemann and Hamrah, Pedram and Brandt, Alexander U}
}
@article {1580489,
	title = {Analysis of vision screening failures in a school-based vision program (2016-19)},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Feb 15},
	abstract = {BACKGROUND: Vision screenings of a school-based program were conducted in state-mandated grades (pre-kindergarten [pre-K] or kindergarten [K], 1st and 8th grade), and nonmandated grades (2nd to 7th). METHODS: During school years 2016-19, 51,593 pre-K to 8th grade students from 123 Baltimore City Public Schools underwent vision screenings, with 85\% of the schools qualifying for Free and Reduced Price Meals. Assessments included distance visual acuity, Spot photoscreening, stereopsis, and cover testing. Screening failures were analyzed by grade using aggregate data. Failure rates for mandated and nonmandated grades were compared using a logistic regression model, and visual acuity distributions were analyzed using individual data. RESULTS: Over the 3-year period, 17,414 (34\%) of students failed vision screening. Failure rates by grade ranged from 28\% to 38\%. Children in kindergarten and 3rd grade and higher were statistically more likely to fail screening than those in 1st grade. Reduced visual acuity was the most common reason for failure (91\%). Failure rates were significantly higher in nonmandated grades than in state-mandated testing grades (34.7\% vs 32.5\% [P \&lt; 0.001]). Mean visual acuity of all students who failed vision screening was 20/50 in the worse-seeing eye and was 20/40 in the better-seeing eye. CONCLUSIONS: One-third of students failed vision screening. High screening failure rates across all grades suggest that screening in select grade levels, as currently mandated in Maryland schools, is inadequate for detecting vision problems in the low-income communities served by this program.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.09.006},
	author = {Milante, Rachel R and Guo, Xinxing and Neitzel, Amanda J and Kretz, Alyssa M and Mukherjee, M Rani and Friedman, David S and Repka, Michael X and Collins, Megan E}
}
@article {669331,
	title = {VEGF: From Discovery to Therapy: The Champalimaud Award Lecture.},
	journal = {Transl Vis Sci Technol},
	volume = {5},
	number = {2},
	year = {2016},
	month = {2016 Mar},
	pages = {9},
	abstract = {PURPOSE: Intraocular vascular diseases are leading causes of adult vision loss, and in the mid-1900s, I. C. Michaelson postulated that the retina releases a soluble, diffusible factor that causes abnormal vascular growth and leakage. What became known as "Factor X" eluded investigators for decades. METHODS: The field of cancer research, where Judah Folkman pioneered the concept of angiogenesis, provided the inspiration for the work honored by the 2014 Champalimaud Vision Award. Recognizing that tumors recruit their own blood supply to achieve critical mass, Dr Folkman proposed that angiogenic factors could be therapeutic targets in cancer. Napoleone Ferrara identified vascular endothelial growth factor (VEGF) as such an angiogenic agent: stimulated by hypoxic tumor tissue, secreted, and able to induce neovascularization. VEGF also was a candidate for Factor X, and the 2014 Champalimaud Laureates and colleagues worked individually and collaboratively to identify the role of VEGF in ocular disease. RESULTS: The Champalimaud Laureates correlated VEGF with ocular neovascularization in animal models and in patients. Moreover, they showed that VEGF not only was sufficient, but it also was required to induce neovascularization in normal animal eyes, as VEGF inhibition abolished ocular neovascularization in key animal models. CONCLUSIONS: The identification of VEGF as Factor X altered the therapeutic paradigms for age-related macular degeneration (AMD), diabetic retinopathy, retinal vein occlusion, and other retinal disorders. TRANSLATIONAL RELEVANCE: The translation of VEGF from discovery to therapy resulted in the most successful applications of antiangiogenic therapy to date. Annually, over one million patients with eye disease are treated with anti-VEGF agents.},
	issn = {2164-2591},
	doi = {10.1167/tvst.5.2.9},
	author = {Miller, Joan W}
}
@article {1363161,
	title = {Vascular endothelial growth factor a in intraocular vascular disease},
	journal = {Ophthalmology},
	volume = {120},
	number = {1},
	year = {2013},
	month = {2013 Jan},
	pages = {106-14},
	abstract = {UNLABELLED: The vascular beds supplying the retina may sustain injury as a result of underlying disease such as diabetes, and/or the interaction of genetic predisposition, environmental insults, and age. The vascular pathologic features observed in different intraocular vascular diseases can be categorized broadly as proliferation, exemplified by proliferative diabetic retinopathy, leakage such as macular edema secondary to retinal vein occlusion, or a combination of proliferation and leakage, as seen in neovascular age-related macular degeneration (AMD). The World Health Organization has identified diabetic retinopathy and AMD as priority eye diseases for the prevention of vision loss in developed countries. The pathologic transformations of the retinal vasculature seen in intraocular vascular disease are associated with increased expression of vascular endothelial growth factor A (VEGF), a potent endothelial-specific mitogen. Furthermore, in model systems, VEGF alone is sufficient to trigger intraocular neovascularization, and its inhibition is associated with functional and anatomic improvements in the affected eye. Therapeutic interventions with effect on VEGF include intraocular capture and neutralization by engineered antibodies or chimeric receptors, downregulation of its expression with steroids, or alleviation of retinal ischemia, a major stimulus for VEGF expression, with retinal ablation by laser treatment. Data from prospective randomized clinical trials indicate that VEGF inhibition is a potent therapeutic strategy for intraocular vascular disease. These findings are changing clinical practice and are stimuli for further study of the basic mechanisms controlling intraocular angiogenesis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Angiogenesis Inhibitors, Capillary Permeability, Diabetic Retinopathy, Humans, Macular Degeneration, Retinal Vein Occlusion, Vascular Endothelial Growth Factor A},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2012.07.038},
	author = {Miller, Joan W and Le Couter, Jennifer and Strauss, Erich C and Ferrara, Napoleone}
}
@article {1782226,
	title = {Perspectives of Resident and Attending Ophthalmologists on Common Ethical Dilemmas in Research},
	journal = {J Acad Ophthalmol (2017)},
	volume = {15},
	number = {2},
	year = {2023},
	month = {2023 Jul},
	pages = {e237-e242},
	abstract = {Purpose   To assess how resident and attending ophthalmologists perceive and evaluate ethically controversial scenarios regarding mentorship, authorship, and ethics compliance that may occur during research involving residents. Methods   An online survey was developed and contained 14 controversial vignettes based on common research scenarios that can occur when conducting research with trainees. The scenarios were designed to capture issues regarding three themes: mentorship, authorship, and compliance with ethical guidelines. Resident and attending ophthalmologists at eight military and civilian academic residency programs in the United States were invited to participate. Respondents used a Likert scale to assess the ethicality of the situations in addition to self-reported demographic characteristics. Results   The response rate was 35.6\% (77/216), consisting of 37.7\% ( n  = 29) residents and 62.3\% ( n  = 48) attendings. More attending ophthalmologists responded than residents ( p  = 0.004). Many respondents identified controversies around compliance (67.3\%) and authorship (57.1\%) as unethical, whereas situations regarding mentorship were largely viewed as neutral to ethical (68.0\%). Responses to two scenarios, one regarding mentorship and one regarding authorship, significantly differed between residents and attendings ( p  = 0.001 and p  = 0.022, respectively). Conclusion   Academic ophthalmologists{\textquoteright} perceptions of the ethicality of common research scenarios varied. There is a need for more prescriptive guidelines for authorship and mentorship ethics at all training levels to ensure consistency, fairness, and integrity of research.},
	issn = {2475-4757},
	doi = {10.1055/s-0043-1774394},
	author = {Miller, Sarah C and Tsou, Brittany C and Fliotsos, Michael J and Legault, Gary L and Wang, Jiangxia and Mondzelewski, Todd J and Munson, Patrick D and Lorch, Alice and Green, Laura K and Kim, Won I and Pelton, Ron W and Woreta, Fasika A and Justin, Grant A}
}
@article {1608609,
	title = {Global Current Practice Patterns for the Management of Open Globe Injuries},
	journal = {Am J Ophthalmol},
	volume = {234},
	year = {2022},
	month = {2022 Feb},
	pages = {259-273},
	abstract = {PURPOSE: To determine global current practice patterns for the management of open globe injuries and identify areas of variation. DESIGN: Cross-sectional survey. METHODS: An online survey assessed global management paradigms for open globe injuries from August 2020 to January 2021. Responses were collected from experts at eye trauma centers and emergency departments worldwide who manage >=1 open globe injury per month. The survey assessed the use/selection of antibiotics and steroids, procedural and imaging decisions, and admission practices for open globe injuries. RESULTS: Responses were received from representatives of 36 of 42 institutions (85.7\%), of which 33 (78.6\%) had sufficient trauma volume to be included. Included responses were distributed across North America (n=12, 36.4\%), Asia (n=12, 36.4\%), South America (n=4, 12.1\%), Africa (n=3, 9.1\%), Europe (n=1, 3.0\%), and Australia (n=1, 3.0\%). Preoperative systemic antibiotics for open globe injuries were administered by 75.8\% (n\&nbsp;=\&nbsp;25/33) of institutions, while 30.3\% (n\&nbsp;=\&nbsp;10/33) administered preoperative topical antibiotics. Intraoperative ophthalmic antibiotics for open globe injuries were used by 54.5\% (n\&nbsp;=\&nbsp;18/33) of experts. Most institutions also administered postoperative systemic antibiotics (n\&nbsp;=\&nbsp;23 [69.7\%]) and topical steroids (n\&nbsp;=\&nbsp;29 [87.9\%]), although specific medication choices diverged. At 19 responding centers (61.3\% of the 31 that had trainees), residents participated in surgical repairs. Many institutions discharged patients after repair, but 54.5\% (n\&nbsp;=\&nbsp;18/33) of locations routinely admitted them for observation. CONCLUSIONS: Preferred management practices for open globe injuries vary widely. To ensure the highest standard of care for all patients, evidence-based international guidelines for the treatment of these injuries are needed.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.08.003},
	author = {Miller, Sarah C and Fliotsos, Michael J and Justin, Grant A and Yonekawa, Yoshihiro and Chen, Ariel and Hoskin, Annette K and Blanch, Richard J and Cavuoto, Kara and Meeralakshmi, Prajna and Low, Rebecca and Gardiner, Matthew and Liu, Tin Yan Alvin and Agrawal, Rupesh and Woreta, Fasika A and International Globe and Adnexal Trauma Epidemiology Study (IGATES)}
}
@article {1470986,
	title = {Developing Therapies for Age-related Macular Degeneration: The Art and Science of Problem-solving: The 2018 Charles L. Schepens, MD, Lecture},
	journal = {Ophthalmol Retina},
	volume = {3},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {900-909},
	abstract = {PURPOSE: To review the roles of analytic and innovative thought in advancing knowledge, using past examples in ophthalmology, and to explore potential strategies to improve our understanding of age-related macular degeneration (AMD) and develop new therapies. DESIGN: Presented as the 2018 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on October 26,\&nbsp;2018. PARTICIPANTS: None. METHODS: Review of published literature and sources on creativity and innovation. MAIN OUTCOME MEASURES: Recommendations for future AMD research. RESULTS: Innovative solutions to problems often seem intuitively obvious in hindsight. Yet, some problems seem impossible to solve. In the 1990s, AMD was a significant unmet need, with only destructive therapies for neovascular disease. This changed with the development of 2 therapies: (1) verteporfin photodynamic therapy (PDT) and (2) anti-vascular endothelial growth factor (VEGF) therapies, which are now administered to millions of people annually around the world. Now, we are frustrated by the lack of therapies for early and intermediate AMD and geographic atrophy. Photodynamic therapy and anti-VEGF drug development occurred through a combination of analytic thought and creative disruption through innovation. To get past our current impasse in understanding and treating AMD, we need to harness both analysis and innovation. We have many important building blocks in place-information on genetics, clinical findings, imaging, and histology-and have identified key pathways and potential therapeutic targets. Perhaps we need additional investigation, analysis, and integration to improve our understanding through work on structure/function and genotype/phenotype correlations and development of imaging and systemic biomarkers. We likely also need an innovative disruption. This innovation might be the concept that there are subtypes of early and intermediate AMD characterized by specific clinical phenotypes, genotype, functional characteristics, and biomarkers that are dependent on particular pathways and treatable with a specific agent. We need to encourage innovation in each of us within our research and clinical community. CONCLUSIONS: Although we have accumulated extensive knowledge about AMD, we are currently at an impasse in the development of new treatments. We need to continue the analytic process, but at the same time encourage innovative disruption to develop successful AMD therapies.},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.07.015},
	author = {Miller, Joan W}
}
@article {1328897,
	title = {Breaking and Sealing Barriers in Retinal Gene Therapy},
	journal = {Mol Ther},
	year = {2018},
	month = {2018 Aug 11},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2018.08.003},
	author = {Miller, Joan W and Vandenberghe, Luk H}
}
@article {560251,
	title = {Long-term Follow-up and Outcomes in Traumatic Macular Holes.},
	journal = {Am J Ophthalmol},
	volume = {160},
	number = {6},
	year = {2015},
	month = {2015 Dec},
	pages = {1255-1258.e1},
	abstract = {PURPOSE: To review presenting characteristics, clinical course, and long-term visual and anatomic outcomes of patients with traumatic macular holes at a tertiary referral center. DESIGN: Retrospective case series. METHODS: Twenty-eight consecutive patients with traumatic macular holes at a single tertiary referral center were reviewed. In addition to visual acuities and treatments throughout the clinical course, specific dimensions of the macular hole, including diameters, height, configuration, shape, and the presence of a cuff of fluid, were examined using spectral-domain optical coherence tomography (OCT). RESULTS: Twenty-eight patients were identified with a mean initial visual acuity (VA) of logMAR 1.3 (20/400) and a mean follow-up of 2.2 years. Eleven holes (39.3\%) closed spontaneously in median 5.7\&nbsp;weeks. Eleven underwent vitrectomy with a median time to intervention of 35.1\&nbsp;weeks. Median time to surgery for the 5 eyes with successful hole closure was 11.0\&nbsp;weeks vs 56.3\&nbsp;weeks for the 6 eyes that failed to close (P\&nbsp;= .02). VA improved in closed holes (P \&lt; .01), whether spontaneously (P \&lt; .01) or via vitrectomy (P\&nbsp;= .04), but VA did not improve in holes that did not close (P\&nbsp;= .22). There was no relation between initial OCT dimensions and final hole closure status, although there was a trend, which did not reach statistical significance, toward small dimensions for those that closed spontaneously. CONCLUSIONS: A fairly high spontaneous closure rate was observed, with a trend toward smaller OCT dimensions. We found no relationship between hole closure and the OCT characteristics of the hole. Surgical intervention was less successful at hole closure when elected after 3\&nbsp;months.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.09.004},
	author = {Miller, John B and Yonekawa, Yoshihiro and Eliott, Dean and Kim, Ivana K and Kim, Leo A and Loewenstein, John I and Sobrin, Lucia and Young, Lucy H and Mukai, Shizuo and Vavvas, Demetrios G}
}
@article {1709706,
	title = {Patient and Visit Characteristics Associated With Otolaryngology Telemedicine Care},
	journal = {Ann Otol Rhinol Laryngol},
	volume = {132},
	number = {12},
	year = {2023},
	month = {2023 Dec},
	pages = {1682-1685},
	abstract = {BACKGROUND: Clinicians are increasingly adopting telemedicine in an effort to expand patient access and efficiently deliver care. The degree of health disparities among patients receiving otolaryngologic telemedical care is unclear. AIMS: We performed a retrospective cross-sectional study to explore disparities in telemedicine delivery. METHODS: We evaluated otolaryngology clinical visits from January 2019 to November 2022. We obtained patient demographics and visit characteristics (e.g., subspecialty, telemedicine vs in-person). Our primary outcome was demographic characteristics of otolaryngology patients who received telemedicine vs in-person care during the study timeframe. RESULTS: A total of 231,384 otolaryngology clinical visits were reviewed, of which 26,895 (11.6\%) were telemedicine visits. Rhinology (36.5\%) and facial plastics (28.4\%) subspecialties performed the most telemedicine visits. On multivariate analysis, individuals who identified as Asian, non-English speaking, and with Medicare insurance were statistically significantly less likely to use telemedicine than in-person services. CONCLUSION: Our findings suggest that expanding telemedicine care may not improve access for all populations, and socioeconomic factors are important considerations to ensure patients are receiving equally accessible care. Futures studies are warranted to understand how these disparities may impact health outcomes and patient satisfaction with care.},
	keywords = {Aged, Cross-Sectional Studies, Humans, Medicare, Otolaryngology, Retrospective Studies, Telemedicine, United States},
	issn = {1943-572X},
	doi = {10.1177/00034894231180009},
	author = {Miller, Lauren E and Xu, Lucy and Lorch, Alice C and Armstrong, Grayson W and Agarwala, Aalok V and Naunheim, Matthew R}
}
@article {1363160,
	title = {Age-related macular degeneration revisited--piecing the puzzle: the LXIX Edward Jackson memorial lecture},
	journal = {Am J Ophthalmol},
	volume = {155},
	number = {1},
	year = {2013},
	month = {2013 Jan},
	pages = {1-35.e13},
	abstract = {PURPOSE: To present the current understanding of age-related macular degeneration (AMD) pathogenesis, based on clinical evidence, epidemiologic data, histopathologic examination, and genetic data; to provide an update on current and emerging therapies; and to propose an integrated model of the pathogenesis of AMD. DESIGN: Review of published clinical and experimental studies. METHODS: Analysis and synthesis of clinical and experimental data. RESULTS: We are closer to a complete understanding of the pathogenesis of AMD, having progressed from clinical observations to epidemiologic observations and clinical pathologic correlation. More recently, modern genetic and genomic studies have facilitated the exploration of molecular pathways. It seems that AMD is a complex disease that results from the interaction of genetic susceptibility with aging and environmental factors. Disease progression also seems to be driven by a combination of genetic and environmental factors. CONCLUSIONS: Therapies based on pathophysiologic features have changed the paradigm for treating neovascular AMD. With improved understanding of the underlying genetic susceptibility, we can identify targets to halt early disease and to prevent progression and vision loss.},
	keywords = {Humans, Macular Degeneration},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2012.10.018},
	author = {Miller, Joan W}
}
@article {1351170,
	title = {The Harvard angiogenesis story},
	journal = {Surv Ophthalmol},
	volume = {59},
	number = {3},
	year = {2014},
	month = {2014 May-Jun},
	pages = {361-4},
	abstract = {I shall discuss the work of researchers at Harvard Medical School who came together in the early 1990s. Scattered across various Harvard-affiliated hospitals and research centers, these individuals were unified by their interest in ocular neovascularization. Together and separately, they investigated models of ocular neovascularization, exploring tumor angiogenesis in eye development and disease.},
	keywords = {Academic Medical Centers, Biomedical Research, Choroidal Neovascularization, Humans, Macular Degeneration, Neoplasms, Neovascularization, Pathologic, Vascular Endothelial Growth Factor A},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2013.07.003},
	author = {Miller, Joan W}
}
@article {1789246,
	title = {Enhancing Pressure Injury Surveillance Using Natural Language Processing},
	journal = {J Patient Saf},
	year = {2023},
	month = {2023 Dec 27},
	abstract = {OBJECTIVE: This study assessed the feasibility of nursing handoff notes to identify underreported hospital-acquired pressure injury (HAPI) events.

METHODS: We have established a natural language processing-assisted manual review process and workflow for data extraction from a corpus of nursing notes across all medical inpatient and intensive care units in a tertiary care pediatric center. This system is trained by 2 domain experts. Our workflow started with keywords around HAPI and treatments, then regular expressions, distributive semantics, and finally a document classifier. We generated 3 models: a tri-gram classifier, binary logistic regression model using the regular expressions as predictors, and a random forest model using both models together. Our final output presented to the event screener was generated using a random forest model validated using derivation and validation sets.

RESULTS: Our initial corpus involved 70,981 notes during a 1-year period from 5484 unique admissions for 4220 patients. Our interrater human reviewer agreement on identifying HAPI was high (κ = 0.67; 95\% confidence interval [CI], 0.58-0.75). Our random forest model had 95\% sensitivity (95\% CI, 90.6\%-99.3\%), 71.2\% specificity (95\% CI, 65.1\%-77.2\%), and 78.7\% accuracy (95\% CI, 74.1\%-83.2\%). A total of 264 notes from 148 unique admissions (2.7\% of all admissions) were identified describing likely HAPI. Sixty-one described new injuries, and 64 describe known yet possibly evolving injuries. Relative to the total patient population during our study period, HAPI incidence was 11.9 per 1000 discharges, and incidence rate was 1.2 per 1000 bed-days.

CONCLUSIONS: Natural language processing-based surveillance is proven to be feasible and high yield using nursing handoff notes.},
	issn = {1549-8425},
	doi = {10.1097/PTS.0000000000001193},
	author = {Milliren, Carly E and Ozonoff, Al and Fournier, Kerri A and Welcher, Jennifer and Landschaft, Assaf and Kimia, Amir A}
}
@article {1532337,
	title = {Lacrimal Gland Hamartoma (Formerly Termed Dacryoadenoma)},
	journal = {Am J Ophthalmol},
	volume = {217},
	year = {2020},
	month = {2020 09},
	pages = {189-197},
	abstract = {PURPOSE: Since the original description of "dacryadenoma" by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion. DESIGN: Retrospective observational case series. METHODS: Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded. RESULTS: Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75\%), or nasal (1/4, 25\%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75\%) or associated with foreign body sensation (1/4, 25\%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50\%) or rare (2/2, 50\%) ducts and rare acinar zymogen granules (3/4, 75\%). CONCLUSION: Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.04.015},
	author = {Milman, Tatyana and Jakobiec, Frederick A and Lally, Sara E and Shields, Jerry A and Shields, Carol L and Eagle, Ralph C}
}
@article {469046,
	title = {Paraproteinemic Keratopathy: The Expanding Diversity of Clinical and Pathologic Manifestations.},
	journal = {Ophthalmology},
	volume = {122},
	number = {9},
	year = {2015},
	month = {2015 Sep},
	pages = {1748-56},
	abstract = {PURPOSE: To describe 7 patients with paraproteinemic keratopathy and to highlight the clinical and pathologic diversity of this rare entity and the importance of timely, systemic evaluation. DESIGN: Retrospective, multicenter collaborative case series. PARTICIPANTS: Seven patients with paraproteinemic keratopathy. METHODS: Clinical and pathologic records were reviewed to identify patients with well-documented corneal immunoglobulin deposits. Detailed ophthalmologic and medical histories were assembled. In 6 patients, corneal tissue was evaluated histochemically and immunohistochemically; in selected cases, corneal tissue was evaluated by in situ hybridization and ultrastructurally. MAIN OUTCOME MEASURES: Visual acuity and anterior segment examination at presentation and follow-up; local therapy; systemic diagnosis and management; and histopathologic, immunohistochemical, in situ hybridization, and ultrastructural findings. RESULTS: Seven patients were identified with corneal immunoglobulin deposition. In addition to previously reported crystalline, nummular, patch-like, and lattice-like corneal opacities, prominent corneal vascularization was present in 2 patients mimicking interstitial keratitis and limbal stem cell deficiency. All patients had evidence of paraproteinemia in a setting of monoclonal gammopathy of undetermined significance, smoldering plasma cell myeloma, or Waldenstr{\"o}m macroglobulinemia. Corneal findings were the first manifestation of systemic disease in 4 patients, and the diagnosis was not suspected in 3 of these patients. Pathologic evaluation of biopsied corneal and conjunctival tissues demonstrated immunoglobulin deposits. Previously unreported ultrastructural patterns in the cornea were noted: large scroll-like immunotactoid deposits, immune complex-like deposits, and randomly arranged fibrils morphologically intermediate between amyloid and immunotactoid deposits. Surgical intervention to improve vision was performed in 4 patients, with recurrence of deposits in 3 patients. Three patients underwent systemic therapy with diminution of the deposits and improvement in vision in 1 patient. CONCLUSIONS: The clinical and pathologic expressions of corneal immunoglobulin deposits are protean and present a diagnostic challenge. Early recognition of this rare entity is important to address the potentially serious associated systemic disease.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.05.029},
	author = {Milman, Tatyana and Kao, Andrew A and Chu, David and Gorski, Matthew and Steiner, Annie and Simon, Carrie Zaslow and Shih, Carolyn and Aldave, Anthony J and Eagle, Ralph C and Jakobiec, Frederick A and Udell, Ira}
}
@article {1517203,
	title = {In Vivo Quasi-Elastic Light Scattering Eye Scanner Detects Molecular Aging in Humans},
	journal = {J Gerontol A Biol Sci Med Sci},
	volume = {75},
	number = {9},
	year = {2020},
	month = {2020 Sep 16},
	pages = {e53-e62},
	abstract = {The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. The human lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, accumulate molecular alterations throughout life, and are optically accessible in vivo. We used quasi-elastic light scattering (QLS) to measure age-dependent signals in lenses of healthy human subjects. Age-dependent QLS signal changes detected in vivo recapitulated time-dependent changes in hydrodynamic radius, protein polydispersity, and supramolecular order of human lens proteins during long-term incubation (~1 year) and in response to sustained oxidation (~2.5 months) in vitro. Our findings demonstrate that QLS analysis of human lens proteins provides a practical technique for noninvasive assessment of molecular aging in vivo.},
	issn = {1758-535X},
	doi = {10.1093/gerona/glaa121},
	author = {Minaeva, Olga and Sarangi, Srikant and Ledoux, Danielle M and Moncaster, Juliet A and Parsons, Douglas S and Washicosky, Kevin J and Black, Caitlin A and Weng, Frank J and Ericsson, Maria and Moir, Robert D and Tripodis, Yorghos and Clark, John I and Tanzi, Rudolph E and Hunter, David G and Goldstein, Lee E}
}
@article {1586169,
	title = {Risk of Cataract in Intermediate Uveitis},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 Mar 10},
	abstract = {PURPOSE: To determine the incidence of and predictive factors for cataract in intermediate uveitis. DESIGN: Retrospective cohort study METHODS: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study, in which medical records were reviewed to determine demographic and clinical data of every eye/patient at every visit at five participating United States tertiary care uveitis centers. The primary outcome was development of vision-compromising cataract as defined by a decrease in visual acuity to 20/40 or less, or requiring cataract surgery. Survival analysis assessed visually defined cataract to avoid bias due to timing of surgery vis-{\`a}-vis inflammatory status. RESULTS: Among 2,190 eyes of 1,302 patients with intermediate uveitis the cumulative incidence of cataract formation was 7.6\% by one year (95\% CI=6.2-9.1\%), increasing to 36.6\% by ten years (95\% CI=31.2-41.6\%). Increased cataract risk was observed in eyes with concurrent anterior uveitis causing posterior synechiae (HR=2.68, 95\% CI=2.00-3.59, p\&lt;0.001), and in eyes with epiretinal membrane formation (HR=1.54, 95\% CI=1.15-2.07, p=0.004). Higher dose corticosteroid therapy was associated with significantly higher incidence of cataract, especially time-updated use of topical corticosteroids >=2 times/day or >=4 periocular corticosteroid injections. Low dose corticosteroid medications (oral prednisone 7.5mg daily or less, or topical corticosteroid drops \&lt;2 times/day) were not associated with increased cataract risk. CONCLUSIONS: Our study found that the incidence of clinically important cataract in intermediate uveitis is moderate. The risk is higher with markers of severity, and with higher doses of corticosteroid medications, the latter being potentially modifiable.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.02.032},
	author = {Minkus, Caroline L and Pistilli, Maxwell and Dreger, Kurt A and Fitzgerald, Tonetta D and Payal, Abhishek R and Begum, Hosne and Ka{\c c}maz, R Oktay and Jabs, Douglas A and Nussenblatt, Robert B and Rosenbaum, James T and Levy-Clarke, Grace A and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Bhatt, Nirali P and Foster, C Stephen and Buchanich, Jeanine M and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study Research Group}
}
@article {1179176,
	title = {Communication Skills Training in Ophthalmology: Results of a Needs Assessment and Pilot Training Program},
	journal = {J Surg Educ},
	year = {2017},
	month = {2017 Sep 01},
	abstract = {OBJECTIVE: To conduct a needs assessment to identify gaps in communication skills training in ophthalmology residency programs and to use these results to pilot a communication workshop that prepares residents for difficult conversations. DESIGN: A mixed-methods design was used to perform the needs assessment. A pre-and postsurvey was administered to workshop participants. SETTING: Mass Eye and Ear Infirmary, Harvard Medical School (HMS), Department of Ophthalmology. PARTICIPANTS: HMS ophthalmology residents from postgraduate years 2-4 participated in the needs assessment and the workshop. Ophthalmology residency program directors in the United States participated in national needs assessment. METHODS: Ophthalmology program directors across the United States were queried on their perception of resident communication skills training through an online survey. A targeted needs assessment in the form of a narrative exercise captured resident perspectives on communication in ophthalmology from HMS residents. A group of HMS residents participated in the pilot workshop and a pre- and postsurvey was administered to participants to assess its effectiveness. RESULTS: The survey of program directors yielded a response rate of 40\%. Ninety percent of respondents agreed that the communication skills training in their programs could be improved. Fifteen of 24 residents (62\%) completed the needs assessment. Qualitative analysis of the narrative material revealed four themes; (1) differing expectations, (2) work role and environment, (3) challenges specific to ophthalmology, and (4) successful strategies adopted. Nine residents participated in the workshop. There was a significant improvement post-workshop in resident reported scores on their ability to manage their emotions during difficult conversations (p = 0.03). CONCLUSIONS: There is an opportunity to improve communication skills training in ophthalmology residency through formalized curriculum.},
	issn = {1878-7452},
	doi = {10.1016/j.jsurg.2017.08.011},
	author = {Mishra, Anuradha and Browning, David and Haviland, Miriam J and Jackson, Mary Lou and Luff, Donna and Meyer, Elaine C and Talcott, Katherine and Kloek, Carolyn E}
}
@article {1360112,
	title = {Minimal memory for details in real life events},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Nov 12},
	pages = {16701},
	abstract = {The extent to which the details of past experiences are retained or forgotten remains controversial. Some studies suggest massive storage while others describe memories as fallible summary recreations of original events. The discrepancy can be ascribed to the content of memories and how memories are evaluated. Many studies have focused on recalling lists of words/pictures, which lack the critical ingredients of real world memories. Here we quantified the ability to remember details about one hour of real life. We recorded video and eye movements while subjects walked along specified routes and evaluated whether they could distinguish video clips from their own experience from foils. Subjects were minimally above chance in remembering the minutiae of their experiences. Recognition of specific events could be partly explained by a machine-learning model of video contents. These results quantify recognition memory for events in real life and show that the details of everyday experience are largely not retained in memory.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-33792-2},
	author = {Misra, Pranav and Marconi, Alyssa and Peterson, Matthew and Kreiman, Gabriel}
}
@article {1580488,
	title = {Psychometric validation techniques applied to the IND-VFQ-33 visual function questionnaire: the Hyderabad ocular morbidity in the elderly study (HOMES)},
	journal = {BMC Med Res Methodol},
	volume = {21},
	number = {1},
	year = {2021},
	month = {2021 Feb 05},
	pages = {26},
	abstract = {BACKGROUND: Over 2 billion people suffer from vision impairment or blindness globally, and access to validated visual measurement tools in imperative in accurately describing and managing the burden of eye disease. The present study applies contemporary psychometric validation techniques to the widely used 33-item Indian Visual Function Questionnaire (IND-VFQ-33). METHODS: We first estimated the polychoric correlation between each pair of items. Next, an unrotated and oblique Promax rotated factor analysis, item response theory (IRT, using a graded response model (GRM)), and differential item functioning (DIF) testing were applied to the IND-VFQ-33. We subsequently propose a validated IND-VFQ-33 questionnaire after psychometric testing, data reduction, and adjustment. RESULTS: Exploratory unrotated factor analysis identified two factors; one with a particularly high eigenvalue (18.1) and a second with a lower eigenvalue still above our threshold (1.1). A subsequent oblique Promax factor rotation was undertaken for a 2-factor solution, revealing two moderately correlated factors (+ 0.68) with clinically discrete item loadings onto either Factor 1 (21 items; collectively labelled "daily activities") or Factor 2 (5 items; collectively labelled "bright lights"). IRT confirmed high item discrimination for all remaining items with good separation between difficulty thresholds. We found significant DIF on depression for six items in Factor 1 (all uniform DIF, except item 21 (non-uniform DIF) with no substantive difference in beta thresholds for any item and no substantive difference in expected individual or sum score, by depression at baseline. For Factor 2, only one item demonstrated significant uniform DIF on gender, similarly without major differences in beta thresholds or expected total score between gender at baseline. Consequently, no further item recalibration or reduction was undertaken after IRT and DIF analysis. CONCLUSION: Applying IRT and DIF validation techniques to the IND-VFQ-33 identified 2 discrete factors with 26 uniquely-loading items, clinically representative of difficulty performing daily activities and experiencing difficulty due to bright lights/glare respectively. The proposed modified scale may be useful in evaluating symptomatic disease progression or response to treatment in an Indian population.},
	issn = {1471-2288},
	doi = {10.1186/s12874-021-01217-w},
	author = {Mitchell, William and Marmamula, Srinivas and Zebardast, Nazlee and Ng, Weiwen and Locascio, Joseph J and Kumbam, Thirupathi and Brahmanandam, Satya and Barrenkala, Navya Rekha}
}
@article {1638553,
	title = {Predictors of long-term intraocular pressure control after lens extraction in primary angle closure glaucoma: results from the EAGLE trial},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {1072-1078},
	abstract = {BACKGROUND/AIMS: To assess baseline ocular parameters in the prediction of long-term intraocular pressure (IOP) control after clear lens extraction (CLE) or laser peripheral iridotomy (LPI) in patients with primary angle closure (PAC) disease using data from the Effectiveness of Early Lens Extraction for the treatment of primary angle-closure glaucoma (EAGLE) tria. METHODS: This study is a secondary analysis of EAGLE data where we define the primary outcome of {\textquoteright}good responders{\textquoteright} as those with IOP\&lt;21 mm Hg without requiring additional surgery and {\textquoteright}optimal responders{\textquoteright} as those who in addition were medication free, at 36-month follow-up. Primary analysis was conducted using a multivariate logistic regression model to assess how randomised interventions and ocular parameters predict treatment response. RESULTS: A total of 369 patients (182 in CLE arm and 187 in LPI arm) completed the 36-month follow-up examination. After CLE, 90\% met our predefined {\textquoteright}good response{\textquoteright} criterion compared with 67\% in the LPI arm, and 66\% met {\textquoteright}optimal response{\textquoteright} criterion compared with 18\% in the LPI arm, with significantly longer drops/surgery-free survival time (p\&lt;0.05 for all). Patients randomised to CLE (OR=10.1 (6.1 to 16.8)), Chinese (OR=2.3 (1.3 to 3.9)), and those who had not previously used glaucoma drops (OR=2.8 (1.6 to 4.8)) were more likely to maintain long-term optimal IOP response over 36 months. CONCLUSION: Patients with primary angle closure glaucoma/PAC are 10 times more likely to maintain drop-free good IOP control with initial CLE surgery than LPI. Non-Chinese ethnicity, higher baseline IOP and using glaucoma drops prior to randomisation are predictors of worse long-term IOP response.},
	keywords = {Cataract Extraction, Glaucoma, Glaucoma, Angle-Closure, Humans, Intraocular Pressure, Iridectomy, Iris, Laser Therapy, Lens, Crystalline},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-319765},
	author = {Mitchell, William G and Azuara-Blanco, Augusto and Foster, Paul J and Halawa, Omar and Burr, Jennifer and Ramsay, Craig R and Cooper, David and Cochran, Claire and Norrie, John and Friedman, David and Chang, Dolly}
}
@article {1559528,
	title = {Updating the model of eye care for Aboriginal populations in remote Central Australia},
	journal = {Clin Exp Ophthalmol},
	volume = {48},
	number = {9},
	year = {2020},
	month = {2020 Dec},
	pages = {1299-1306},
	abstract = {Eye disease is the third-highest contributor towards health inequality for Aboriginal Australians. Understanding how the Central Australian ophthalmology service addresses complexities of remote eye care is crucial in understanding how expansion can meet current and future needs. The present study analyses findings from the MEDLINE database and Governmental reports, and descriptive information from stakeholders in Central Australia and the Australian Department of Health. We describe the current Central Australian ophthalmology model at three levels; (a) the healthcare service level (specialized primary care, local/outreach optometry and ophthalmology services, and intensive extended surgical weeks), (b) the community level (local community staff, clinics and initiatives, and eye "champions" and mutual support), and (c) the healthcare system level (federal and state government, and private funding). We conclude that building full-time specialist availability, and system-wide approaches to increase patient utilisation, will facilitate overcoming barriers of remoteness, and create enduring improvements in Central Australian eye care and health-inequality.},
	issn = {1442-9071},
	doi = {10.1111/ceo.13838},
	author = {Mitchell, William and Hassall, Mark and Henderson, Tim}
}
@article {1522714,
	title = {Retrospective cross-sectional analysis of the changes in marijuana use in the USA, 2005-2018},
	journal = {BMJ Open},
	volume = {10},
	number = {7},
	year = {2020},
	month = {2020 Jul 28},
	pages = {e037905},
	abstract = {OBJECTIVES: Understanding trends of marijuana use in the USA throughout a period of particularly high adoption of marijuana-legalisation, and understanding demographics most at risk of use, is important in evolving healthcare policy and intervention. This study analyses the demographic-specific changes in the prevalence of marijuana use in the USA between 2005 and 2018. DESIGN, SETTING AND PARTICIPANTS: A 14-year retrospective cross-sectional analysis of the National Health and Nutrition Examination Survey database, a publicly available biennially collected national survey, weighted to represent the entire US population. A total of 35 212 adults between 18 and 69 years old participated in the seven-cycles of surveys analysed (2005-2018). PRIMARY OUTCOME MEASURED: Lifetime use, first use before 18 years old, and past-year use of marijuana. RESULTS: The majority of adults reported ever using marijuana. While the overall prevalence of lifetime marijuana use remained stable (p=0.53), past-year use increased significantly between 2005 and 2018 (p\&lt;0.001) with highest rate of past-year use among younger age groups (p\&lt;0.001), males (p\&lt;0.001) and those with income below poverty level (p\&lt;0.001). Past-year use was the most common among non-Hispanic blacks, and less common among Hispanic/Mexican populations (p\&lt;0.002). Trends in past-year use increased among all age categories, males/females, all ethnicities, those with high school education/above, and those at all income levels (p\&lt;0.01 for all). CONCLUSIONS: While lifetime marijuana use remained stable, past-year use significantly increased between 2005 and 2018. While past-year use remained the most common in younger age groups, males, non-Hispanic blacks and those with lower income; increasing trends in past-year use were significant for all age, sex, race and income categories, and for those with high school education/above. With high adoption of marijuana-legalisation laws during this period, our results suggest an associated increase in past-year marijuana use.An accurate understanding of those most at risk can help to inform decisions of healthcare policy-makers and professionals, and facilitate a safe transition of changing marijuana legalisation and use in the USA.},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2020-037905},
	author = {Mitchell, William and Bhatia, Roma and Zebardast, Nazlee}
}
@article {931126,
	title = {Restoration of Corneal Transparency by Mesenchymal Stem Cells.},
	journal = {Stem Cell Reports},
	volume = {7},
	number = {4},
	year = {2016},
	month = {2016 Oct 11},
	pages = {583-590},
	abstract = {Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in\&nbsp;vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF). Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy.},
	issn = {2213-6711},
	doi = {10.1016/j.stemcr.2016.09.001},
	author = {Mittal, Sharad K and Omoto, Masahiro and Amouzegar, Afsaneh and Sahu, Anuradha and Rezazadeh, Alexandra and Katikireddy, Kishore R and Shah, Dhvanit I and Sahu, Srikant K and Chauhan, Sunil K}
}
@article {1445337,
	title = {Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor},
	journal = {Stem Cells Transl Med},
	volume = {8},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {1030-1040},
	abstract = {Mesenchymal stromal cells (MSCs) are multipotent stem cells that participate in tissue repair and possess considerable immunomodulatory potential. MSCs have been shown to promote allograft survival, yet the mechanisms behind this phenomenon have not been fully defined. Here, we investigate the capacity of MSCs to suppress the allogeneic immune response by secreting the pleiotropic molecule hepatocyte growth factor (HGF). Using an in vivo mouse model of corneal transplantation, we report that MSCs promote graft survival in an HGF-dependent manner. Moreover, our data indicate that topically administered recombinant HGF (a) suppresses antigen-presenting cell maturation in draining lymphoid tissue, (b) limits T-helper type-1 cell generation, (c) decreases inflammatory cell infiltration into grafted tissue, and (d) is itself sufficient to promote transplant survival. These findings have potential translational implications for the development of HGF-based therapeutics. Stem Cells Translational Medicine 2019;8:1030-1040.},
	issn = {2157-6580},
	doi = {10.1002/sctm.19-0004},
	author = {Mittal, Sharad K and Foulsham, William and Shukla, Sachin and Elbasiony, Elsayed and Omoto, Masahiro and Chauhan, Sunil K}
}
@article {1709686,
	title = {Recurrent Keratoconus: Corneal Transplants for Keratoconus Develop Tomographic Ectatic Changes},
	journal = {Cornea},
	volume = {42},
	number = {6},
	year = {2023},
	month = {2023 Jun 01},
	pages = {708-713},
	abstract = {PURPOSE: The purpose of this study was to evaluate postoperative Scheimpflug imaging changes during the first 5 years after penetrating keratoplasty (PK) in patients with keratoconus (KC). METHODS: This retrospective, interventional case series includes 31 eyes of 31 patients who underwent their first PK with a history of KC. Postoperative Scheimpflug imaging was performed 3 months after the removal of the last suture (baseline) and then repeated 3 and 5 years after the PK. Demographic data, donor and host trephination diameter, and Scheimpflug imaging (Pentacam HR, Oculus, Germany) parameters indicative of ectasia were analyzed to evaluate postoperative graft changes that occur after PK. RESULTS: The maximal keratometry (Kmax) progressed significantly between baseline (53.5 {\textpm} 6.1 D) and postoperative year 3 and year 5 [56.5 {\textpm} 6.1 diopter (D) and 58.8 {\textpm} 7.9 D, P \&lt; 0.001]. Significant changes were also observed for the anterior best fit sphere and posterior best fit sphere ( P \&lt; 0.001 for 3 and 5 years compared with baseline). Kmax increased by at least 2 Ds for 74.2\% of patients and up to 7 Ds or more for 25.8\% of the patients. A significant inverse correlation was observed for host trephine size and progression of Kmax (r = -0.52, P = 0.01), which indicated that larger host trephination size was associated with a smaller increase in postoperative Kmax. CONCLUSIONS: Tomographic graft changes indicative of ectasia were observed within 3 to 5 years after PK in patients with KC. These changes were observed more frequently and sooner after corneal transplants than previously reported.},
	keywords = {Cornea, Corneal Topography, Dilatation, Pathologic, Humans, Keratoconus, Keratoplasty, Penetrating, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003149},
	author = {Miura, Maria and Leon, Pia and Nahum, Yoav and B{\"o}hm, Myriam S and Mimouni, Michael and Belin, Michael W and Johns, Lynette and Ciolino, Joseph B}
}
@article {1478326,
	title = {Loss of NQO1 generates genotoxic estrogen-DNA adducts in Fuchs Endothelial Corneal Dystrophy},
	journal = {Free Radic Biol Med},
	volume = {147},
	year = {2020},
	month = {2020 Feb 01},
	pages = {69-79},
	abstract = {Fuchs Endothelial Corneal Dystrophy (FECD) is an age-related genetically complex disease characterized by increased oxidative DNA damage and progressive degeneration of corneal endothelial cells (HCEnCs). FECD has a greater incidence and advanced phenotype in women, suggesting a possible role of hormones in the sex-driven differences seen in the disease pathogenesis. In this study, catechol estrogen (4-OHE), the byproduct of estrogen metabolism, induced genotoxic estrogen-DNA adducts formation, macromolecular DNA damage, and apoptotic cell death in HCEnCs; these findings were potentiated by menadione (MN)-mediated reactive oxygen species (ROS). Expression of NQO1, a key enzyme that neutralizes reactive estrogen metabolites, was downregulated in FECD, indicating HCEnC susceptibility to reactive estrogen metabolism in FECD. NQO1 deficiency in vitro exacerbated the estrogen-DNA adduct formation and loss of cell viability, which was rescued by the supplementation of N-acetylcysteine, a ROS scavenger. Notably, overexpression of NQO1 in HCEnCs treated with MN and 4-OHE quenched the ROS formation, thereby reducing the DNA damage and endothelial cell loss. This study signifies a pivotal role for NQO1 in mitigating the macromolecular oxidative DNA damage arising from the interplay between intracellular ROS and impaired endogenous estrogen metabolism in post-mitotic ocular tissue cells. A dysfunctional Nrf2-NQO1 axis in FECD renders HCEnCs susceptible to catechol estrogens and estrogen-DNA adducts formation. This novel study highlights the potential role of NQO1-mediated estrogen metabolite genotoxicity in explaining the higher incidence of FECD in females.},
	issn = {1873-4596},
	doi = {10.1016/j.freeradbiomed.2019.12.014},
	author = {Miyajima, Taiga and Melangath, Geetha and Zhu, Shan and Deshpande, Neha and Vasanth, Shivakumar and Mondal, Bodhisattwa and Kumar, Varun and Chen, Yuming and Price, Marianne O and Price, Francis W and Rogan, Eleanor G and Zahid, Muhammad and Jurkunas, Ula V}
}
@article {509176,
	title = {The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {9},
	year = {2015},
	month = {2015 Aug 1},
	pages = {5353-61},
	abstract = {PURPOSE: To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye. METHODS: This is a retrospective, open cohort study consisting of 891 unilateral AMD patients, who were followed for at least 12 months and recruited from three institutes. DNAs were genotyped using Illumina OmniExpress, HumanOmni2.5-8, and/or HumanExome. Survival analyses and Cox proportional hazard models were used to examine the association between 11 AMD susceptibility genes and the duration until second-eye involvement in 499 samples from Kyoto University, which were replicated in two other cohorts. Genetic risk score (GRS) was also evaluated. RESULTS: The ARMS2 rs10490924 recessive model (hazard ratio [HR]meta = 2.04; Pmeta = 3.4 {\texttimes} 10-3) and CFH rs800292 additive model (HRmeta = 1.77; Pmeta = 0.013) revealed significant associations with second-eye involvement. The dominant model of TNFRSF10A rs13278062, VEGFA rs943080, and CFI rs4698775 showed consistent effects across three datasets (I2 = 0\%; HRmeta = 1.46, 1.30, 1.51, respectively). The GRS using these five single nucleotide polymorphisms (SNPs) was also significantly associated (HRmeta [per score] = 2.42; P = 2.2 {\texttimes} 10-5; I2 = 0\%). After 10 years from the first visit, the patients within the top 10\% by GRS showed a 51\% hazard rate, in contrast to 2.3\% among patients within the lowest 10\% by GRS. CONCLUSIONS: We demonstrated that the GRS using ARMS2, CFH, TNFRSF10A, VEGFA, and CFI was significantly associated with second-eye involvement. Genetic risk has high predictive ability for second-eye involvement of AMD.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-16020},
	author = {Miyake, Masahiro and Yamashiro, Kenji and Tamura, Hiroshi and Kumagai, Kyoko and Saito, Masaaki and Sugahara-Kuroda, Masako and Yoshikawa, Munemitsu and Oishi, Maho and Akagi-Kurashige, Yumiko and Nakata, Isao and Nakanishi, Hideo and Gotoh, Norimoto and Oishi, Akio and Matsuda, Fumihiko and Yamada, Ryo and Khor, Chiea-Chuen and Kurimoto, Yasuo and Sekiryu, Tetsuju and Tsujikawa, Akitaka and Yoshimura, Nagahisa}
}
@article {1363162,
	title = {Analysis of gene expression in wild-type and Notch1 mutant retinal cells by single cell profiling},
	journal = {Dev Dyn},
	volume = {242},
	number = {10},
	year = {2013},
	month = {2013 Oct},
	pages = {1147-59},
	abstract = {BACKGROUND: The vertebrate retina comprises sensory neurons, the photoreceptors, as well as many other types of neurons and one type of glial cell. These cells are generated by multipotent and restricted retinal progenitor cells (RPCs), which express Notch1. Loss of Notch1 in RPCs late during retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. RESULTS: To examine the molecular underpinnings of this observation, microarray analysis of single retinal cells from wild-type or Notch1 conditional knockout retinas was performed. In situ hybridization was carried out to validate some of the findings. CONCLUSIONS: The majority of Notch1-mutant cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly up-regulated rod precursor genes. In addition, single wild-type cells, in which cell cycle marker genes were down-regulated, expressed markers of both rod photoreceptors and interneurons.},
	keywords = {Animals, Cell Cycle, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Mice, Mutation, Oligonucleotide Array Sequence Analysis, Receptor, Notch1, Retinal Rod Photoreceptor Cells, Stem Cells},
	issn = {1097-0177},
	doi = {10.1002/dvdy.24006},
	author = {Mizeracka, Karolina and Trimarchi, Jeffrey M and Stadler, Michael B and Cepko, Constance L}
}
@article {1789071,
	title = {Cryptococcal proteases exhibit the potential to activate the latent SARS-CoV-2 spike protein},
	journal = {J Infect Public Health},
	volume = {17},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {263-270},
	abstract = {BACKGROUND: The COVID-19 pandemic has affected more than 650 million people and resulted in over 6.8 million deaths. Notably, the disease could co-manifest with microbial infections, like cryptococcosis, which also presents as a primary lung infection. OBJECTIVE: In this contribution, we sought to determine if cryptococcal supernatant (which contains secreted furin-like proteases) could activate the SARS-CoV-2 spike protein. METHODS: Molecular docking of the crystal structures of the SARS-CoV-2 spike protein (target) and selected cryptococcal proteases (ligands) was executed using the high ambiguity driven protein-protein docking (HADDOCK) server, with the furin protease serving as a reference ligand. The furin protease is found in human cells and typically activates the SARS-CoV-2 spike protein. Importantly, in order to provide experimental evidence for enzymatic activity, we also assessed the biochemical efficiency of cryptococcal proteases to initiate viral entry into HEK-293\&nbsp;T cells by SARS-CoV-2 spike pseudotyped Lentivirus. RESULTS: We show that the selected cryptococcal proteases could interact with the spike protein, and some had a better or comparable binding affinity for the spike protein than furin protease following an in silico comparative analysis of the molecular docking parameters. Furthermore, it was noted that the biochemical efficiency of the cryptococcal supernatant to transduce HEK-293\&nbsp;T cells with SARS-CoV-2 pseudovirions was comparable (p\&nbsp;\&gt;\&nbsp;0.05) to that of recombinant furin. CONCLUSIONS: Taken together, these data show that cryptococcal proteases could activate the SARS-CoV-2 spike protein. In practice, it may be critical to determine if patients have an underlying cryptococcal infection, as this microbe could secrete proteases that may further activate the SARS-CoV-2 viral particles, thus undermining COVID-19 intervention measures.},
	keywords = {COVID-19, Furin, HEK293 Cells, Humans, Molecular Docking Simulation, Pandemics, Peptide Hydrolases, SARS-CoV-2, Spike Glycoprotein, Coronavirus},
	issn = {1876-035X},
	doi = {10.1016/j.jiph.2023.12.008},
	author = {Mjokane, Nozethu and Sabiu, Saheed and Folorunso, Olufemi S and Gcilitshana, Onele M N and Albertyn, Jacobus and Pohl, Carolina H and Sebolai, Olihile M}
}
@article {416871,
	title = {Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome.},
	journal = {Am J Hum Genet},
	volume = {96},
	number = {5},
	year = {2015},
	month = {2015 May 7},
	pages = {753-64},
	abstract = {The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65\% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n\&nbsp;=\&nbsp;562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12\&nbsp;{\texttimes} 10(-3), two-tailed Fisher{\textquoteright}s exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30\&nbsp;{\texttimes} 10(-2), two-tailed Fisher{\textquoteright}s exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68\&nbsp;{\texttimes} 10(-4), two-tailed Fisher{\textquoteright}s exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS.},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2015.03.007},
	author = {Mlynarski, Elisabeth E and Sheridan, Molly B and Xie, Michael and Guo, Tingwei and Racedo, Silvia E and McDonald-McGinn, Donna M and Gai, Xiaowu and Chow, Eva W C and Vorstman, Jacob and Swillen, Ann and Devriendt, Koen and Breckpot, Jeroen and Digilio, Maria Cristina and Marino, Bruno and Dallapiccola, Bruno and Philip, Nicole and Simon, Tony J and Roberts, Amy E and Piotrowicz, Ma{\l}gorzata and Bearden, Carrie E and Eliez, Stephan and Gothelf, Doron and Coleman, Karlene and Kates, Wendy R and Devoto, Marcella and Zackai, Elaine and Heine-Su{\~n}er, Damian and Shaikh, Tamim H and Bassett, Anne S and Goldmuntz, Elizabeth and Morrow, Bernice E and Emanuel, Beverly S and International Chromosome 22q11.2 Consortium}
}
@article {836926,
	title = {Results of a primary care-based quality improvement project to optimize chart-based vision screening for preschool age children.},
	journal = {J AAPOS},
	year = {2016},
	month = {2016 Jul 2},
	abstract = {PURPOSE: To design chart-based vision screening for preschool-aged children. METHODS: Our program consisted of educational sessions for providers as well as hands-on training for practice staff. We evaluated the intervention through pre- and post-intervention review of medical records. RESULTS: Completion of full vision screening (distance visual acuity in each eye plus stereovision beginning at 3 years of age, as recommended at the time of the project) at well-child visits improved for 5-year-olds (45.0\% to 58.2\%; risk difference +13.2\% [95\% CI, 1.7-24.7]) and 4-year-olds (39.3\% to 51.4\%; risk difference +12.0\% [95\% CI, 0.7-23.4]) but declined somewhat among 3-year-olds (23.1\% to 14.3\%; risk difference, -8.8\% [95\% CI, -17.7 to 0.0]). Risk factors for not being fully screened included being 3 years old (risk ratio of 4.1 compared to 5-year-olds) and being a patient of a small practice (risk ratio of 1.9 compared to large practices). CONCLUSIONS: This quality improvement project showed that screening for visual acuity and stereovision among preschool-aged children using chart-based techniques is difficult to accomplish and unlikely to be consistently successful, especially among 3-year-olds.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2016.04.005},
	author = {Modest, Jonathan R and Johnston, Suzanne C and Majzoub, Katherine M and Moore, Bruce and Trudell, Emily K and Ramsey, Jean E and Vernacchio, Louis}
}
@article {603891,
	title = {Optic Nerve Head Avulsion: Clinical, Radiographic, and Sonographic Correlations.},
	journal = {Ophthalmology},
	volume = {122},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {2442},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.09.042},
	author = {Modjtahedi, Bobeck S and Fortenbach, Christopher R and Lorch, Alice C}
}
@article {1478335,
	title = {A new patient-centered approach to ocular surface discomfort},
	journal = {Ocul Surf},
	volume = {18},
	number = {2},
	year = {2020},
	month = {2020 Apr},
	pages = {196-198},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.12.002},
	author = {Modjtahedi, Bobeck S and Jacobs, Deborah S and Fong, Donald S}
}
@article {1318871,
	title = {Public Health Burden and Potential Interventions for Myopia},
	journal = {Ophthalmology},
	volume = {125},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {628-630},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.01.033},
	author = {Modjtahedi, Bobeck S and Ferris, Frederick L and Hunter, David G and Fong, Donald S}
}
@article {314166,
	title = {Imaging characteristics of intraocular foreign bodies: a comparative study of plain film X-ray, computed tomography, ultrasound, and magnetic resonance imaging.},
	journal = {Retina},
	volume = {35},
	number = {1},
	year = {2015},
	month = {2015 Jan},
	pages = {95-104},
	abstract = {PURPOSE: To determine the imaging features of common intraocular foreign bodies (IOFBs) and the ability to differentiate types of IOFBs. METHODS: Four-mm IOFBs were inserted via through pars plana approach into cadaveric lamb eyes. Six metallic (aluminum, brass, copper, silver, steel, and lead) and seven nonmetallic (plastic [CF6 spectacle plastic and polyvinyl chloride pipe], glass [bottle glass and windshield glass], wood [dry and wet poplar], and stone [slate]) IOFBs were imaged using plain film x-ray, computed tomography scan, ultrasound, and magnetic resonance imaging (T1, T2, and gradient echo sequences). RESULTS: Plain film x-ray had limited ability to differentiate most IOFBs. Computed tomography findings can be divided into low attenuation objects (wood), moderate attenuation (CF6 spectacle plastic), high attenuation without surrounding artifact (polyvinyl chloride, slate, bottle glass, windshield glass, and aluminum), high attenuation with shadow artifact and minimal edge streak artifact (steel, brass, copper), and high attenuation with significant shadow artifact and prominent streak artifact (silver and lead). Density (in Hounsfield units) aided in differentiating the types of IOFBs. Gradient echo sequences on magnetic resonance imaging also held utility. Ultrasound images had considerable overlap in appearances. CONCLUSION: Imaging techniques can significantly aid in determining the IOFBs type, with computed tomography serving as the best initial modality. X-ray holds limited utility while ultrasound and magnetic resonance imaging are best reserved as adjunctive tests.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000271},
	author = {Modjtahedi, Bobeck S and Rong, Andrew and Bobinski, Mathew and McGahan, John and Morse, Lawrence S}
}
@article {836931,
	title = {Endophthalmitis After Intravitreal Injections in Patients With Self-reported Iodine Allergy.},
	journal = {Am J Ophthalmol},
	volume = {170},
	year = {2016},
	month = {2016 Oct},
	pages = {68-74},
	abstract = {PURPOSE: To present cases of endophthalmitis following intravitreal injections where povidone-iodine (PI) was not used as part of the surgical preparation. DESIGN: Retrospective case series. METHODS: All cases of presumed injection-related endophthalmitis presenting to the Massachusetts Eye and Ear Infirmary between June 2008 and November 2014 and Dean McGee Eye Institute between January 2010 and January 2015 were identified. Patients who did not receive PI preparation owing to documented self-reported allergy to iodine, iodine-containing contrast material, or shellfish were identified and their injection histories and clinical courses reviewed. RESULTS: The combined rate of postinjection endophthalmitis at these 2 centers was 0.019\%. Among 42 patients with postinjection endophthalmitis, 5 (11.9\%) did not receive PI prophylaxis. The mean number of intravitreal injections without PI before the development of endophthalmitis was 10.6 with a 9.4\% rate of endophthalmitis (5 cases per 53 injections). All patients underwent tap-and-inject procedures with vancomycin 1\&nbsp;mg and ceftazidime 2\&nbsp;mg. Two patients did not receive PI at the time of tap and inject; 1 of these patients required subsequent pars plana vitrectomy for worsening clinical course. Cultures were positive in 4 of 5 cases; all positive cultures grew coagulase-negative Staphylococcus. All patients who received subsequent intravitreal injections received PI prophylaxis without allergic reactions, thus demonstrating a lack of true PI allergy. CONCLUSIONS: Avoiding PI owing to self-reported iodine "allergy" risks substantial ocular morbidity. Allergy testing can be pursued per patient request or in rare cases of suspected true PI allergy; however, in cases where delayed treatment would adversely affect visual outcome, the clinician should feel confident that minimal allergic risk exists.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.07.010},
	author = {Modjtahedi, Bobeck S and van Zyl, Tav{\'e} and Pandya, Hemang K and Leonard, Robert E and Eliott, Dean}
}
@article {1233396,
	title = {Association of Endogenous Endophthalmitis With Intravenous Drug Use: An Emerging Public Health Challenge},
	journal = {JAMA Ophthalmol},
	year = {2017},
	month = {2017 Oct 19},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.4342},
	author = {Modjtahedi, Bobeck S and Finn, Avni P and Eliott, Dean}
}
@article {1522709,
	title = {Visualization of micro-neuromas by using in vivo confocal microscopy: An objective biomarker for the diagnosis of neuropathic corneal pain?},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 Jul 11},
	abstract = {PURPOSE: The diagnosis of neuropathic corneal pain (NCP) is challenging, as it is often difficult to differentiate from conventional dry eye disease (DED). In addition to eye pain, NCP can present with similar signs and symptoms of DED. The purpose of this study is to find an objective diagnostic sign to identify patients with NCP, using in vivo confocal microscopy (IVCM). METHODS: This was a comparative, retrospective, case-control study. Patients with clinical diagnosis of NCP (n = 25), DED (n = 30), and age and sex-matched healthy controls (n = 16), who underwent corneal imaging with IVCM (HRT3/RCM) were included. Central corneal IVCM scans were analyzed by 2 masked observers for nerve density and number, presence of micro-neuromas (terminal enlargements of subbasal corneal nerve) and/or nerve beading (bead-like formation along the nerves), and dendritiform cell (DC) density. RESULTS: There was a decrease in total nerve density in both NCP (14.14 {\textpm} 1.03 mm/mm) and DED patients (12.86 {\textpm} 1.04 mm/mm), as compared to normal controls (23.90 {\textpm} 0.92 mm/mm; p \&lt; 0.001). However, total nerve density was not statistically different between NCP and DED patients (p = 0.63). Presence of nerve beading was not significantly different between patients and normal controls (p = 0.15). Interestingly, micro-neuromas were observed in all patients with NCP, while they were not present in any of the patients with DED (sensitivity and specificity of 100\%). DC density was increased significantly in both NCP (71.89 {\textpm} 16.91 cells/mm) and DED patients (111.5 {\textpm} 23.86 cells/mm), as compared to normal controls (24.81 {\textpm} 4.48 cells/mm (Colloca et al., 2017) [2]; p \&lt; 0.05). However, there was no significant difference in DC density between DED and NCP patients (p = 0.31). CONCLUSION: IVCM may be used as an adjunct diagnostic tool for the diagnosis of NCP in the presence of neuropathic symptoms. Micro-neuromas may serve as a sensitive and specific biomarker for the diagnosis of NCP.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.07.004},
	author = {Moein, Hamid-Reza and Akhlaq, Anam and Dieckmann, Gabriela and Abbouda, Alessandro and Pondelis, Nicholas and Salem, Zeina and M{\"u}ller, Rodrigo T and Cruzat, Andrea and Cavalcanti, Bernardo M and Jamali, Arsia and Hamrah, Pedram}
}
@article {1430533,
	title = {Exposure, entropion, and bilateral corneal ulceration in a newborn as a manifestation of chromosome 22 q11.2 duplication syndrome},
	journal = {Am J Ophthalmol Case Rep},
	volume = {13},
	year = {2019},
	month = {2019 Mar},
	pages = {16-19},
	abstract = {Purpose: Chromosome 22q11.2 micro-duplication syndrome (MDS), is a rare autosomal dominant condition, with a highly variable phenotype that ranges from unremarkable and asymptomatic, to fatal due to cardiovascular defects. Hypertelorism, downslanting palpebral fissures, superior displacement of the eyebrows, and ptosis are the most commonly reported ocular manifestations. Here, we report a newborn with bilateral exposure, entropion, and corneal ulceration related to 22q11.2 MDS. Observation: A newborn girl presented with bilateral upper eyelid entropion, bilateral lower eyelid ectropion, and lagophthalmos. She subsequently developed bilateral corneal ulcers. Topical antibacterial drops, bandage contact lenses, medroxyprogesterone 1\%, and fluorometholone 0.1\%, together with partial tarsorrhaphy and correction of eyelid malposition, were used to treat the ulcers and address the underlying issues of exposure and entropion. Genetic testing revealed chromosome 22q11.2.MDS; further evaluation revealed systemic manifestations of this syndrome. The ocular surface healed well with gradual improvement of corneal opacification as well as bilateral partial tarsorrhaphy. Conclusion and importance: This report is the first that describes a newborn with 22q11.2 MDS presenting with sight-threatening corneal ulceration. Entropion, ectropion, and lagophthalmos were identified and treated, allowing for healing of the corneal surface. Genetic testing revealed a syndrome not known to be associated with eyelid abnormalities and corneal ulceration, but with other important systemic and ocular implications. Bilateral partial tarsorrhaphy should not be excluded as a treatment option for infants who fail more conservative measures for the treatment of exposure.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2018.11.001},
	author = {Moein, Hamid-Reza and Saeed, Hajirah N and Jacobs, Deborah S and Rapoport, Yuna and Yoon, Michael K and Shah, Ankoor S and Khan, Haumith and Raoof, Duna and Jurkunas, Ula V}
}
@article {1295874,
	title = {Corneal nerve regeneration after herpes simplex keratitis: A longitudinal in~vivo confocal microscopy study},
	journal = {Ocul Surf},
	volume = {16},
	number = {2},
	year = {2018},
	month = {2018 Apr},
	pages = {218-225},
	abstract = {PURPOSE: To evaluate the long-term alterations of corneal nerves in patients with herpes simplex virus (HSV) keratitis using in~vivo confocal microscopy (IVCM).

DESIGN: Prospective, longitudinal, cross sectional.

METHODS: This study included 16 patients with a history of HSV keratitis and 15 age-matched normal controls. Slit-scanning IVCM was performed in all subjects at baseline and then after a mean follow-up of 37.3 {\textpm} 1.7 months in the patient group. Corneal subbasal nerve density and corneal sensation were compared between groups at baseline and follow-up.

RESULTS: At baseline, the mean subbasal nerve density was significantly lower in both affected eyes (1.4 {\textpm} 0.6 mm/mm) and contralateral unaffected eyes (6.4 {\textpm} 0.7 mm/mm) compared with the controls (14.1 {\textpm} 1.6 mm/mm; all P ,
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.12.001},
	author = {Moein, Hamid-Reza and Kheirkhah, Ahmad and Muller, Rodrigo T and Cruzat, Andrea C and Pavan-Langston, Deborah and Hamrah, Pedram}
}
@article {1580465,
	title = {Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Feb 19},
	pages = {4267},
	abstract = {To investigate the acute clinical, immunological, and corneal nerve changes following corneal HSV-1 KOS-63 strain inoculation. Corneas of C57BL/6 mice were inoculated with either low dose (Ld) or high dose (Hd) HSV-1 KOS-63 or culture medium. Clinical evaluation was conducted up to 7\&nbsp;days post inoculation (dpi). Viral titers were assessed by standard plaque assay. Excised corneas were stained for CD45 and beta-III tubulin. Corneal flow cytometry was performed to assess changes in leukocyte subpopulations. Corneal sensation was measured using a\&nbsp;Cochet-Bonnet esthesiometer. Na{\"\i}ve, sham-infected (post scarification), and McKrae-infected C57BL/6 corneas served as two negative and positive controls, respectively. Compared to Ld infected mice, Hd HSV-1 KOS-63 demonstrated higher incidence of corneal opacity (1.5 {\texttimes}) and neovascularization (2.6 {\texttimes} ; p \&lt; 0.05). At 7\&nbsp;dpi Hd infected mice showed more severe corneal opacity (2.23 vs. 0.87; p = 0.0003), neovascularization (6.00 vs. 0.75; p \&lt; 0.0001), and blepharitis (3.11 vs. 2.06; p = 0.001) compared to the Ld group. At 3\&nbsp;dpi epitheliopathy was significantly larger in the Hd group (23.59\% vs. 3.44\%; p = 0.001). Similarly, corneal opacity was significantly higher in Hd McKrae-infected corneas as compared with Ld McKrae-infected corneas at 3 and 5 dpi. No significant corneal opacity, neovascularization, blepharitis, and epitheliopathy were observed in na{\"\i}ve or sham-infected mice. Higher viral titers were detected in corneas (1 and 3 dpi) and trigeminal ganglia (TG) (3 and 5 dpi) in Hd versus Ld KOS-63 groups (p \&lt; 0.05). Leukocyte density showed a gradual increase over time from 1 to 7\&nbsp;dpi in both KOS-63 and McKrae-infected corneas. Corneal flow cytometric analysis (3\&nbsp;dpi) demonstrated a higher percentage of Gr-1 + (71.6 vs. 26.3) and CD11b + (90.6 vs. 41.1) cells in Hd versus Ld KOS-63 groups. Corneal nerve density significantly decreased in both Hd KOS-63 and Hd McKrae infected corneas in comparison with na{\"\i}ve and sham-infected corneas. At 3 dpi corneal nerve density was lower in the Hd versus Ld KOS-63 groups (16.79 vs. 57.41\&nbsp;mm/mm2; p = 0.004). Corneal sensation decreased accordingly at 5 and 7\&nbsp;dpi in both Ld and Hd KOS-63-infected mice. Corneal inoculation with HSV-1 KOS-63 strain shows acute keratitis and nerve degeneration in a dose-dependent fashion, demonstrating virulence of this strain.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-83412-9},
	author = {Moein, Hamid-Reza and Sendra, Victor G and Jamali, Arsia and Kheirkhah, Ahmad and Harris, Deshea L and Hamrah, Pedram}
}
@article {1559565,
	title = {With Motion Perception, Good Visual Acuity May Not Be Necessary for Driving Hazard Detection},
	journal = {Transl Vis Sci Technol},
	volume = {9},
	number = {13},
	year = {2020},
	month = {2020 Dec},
	pages = {18},
	abstract = {Purpose: To investigate the roles of motion perception and visual acuity in driving hazard detection. Methods: Detection of driving hazard was tested based on video and still-frames of real-world road scenes. In the experiment using videos, 20 normally sighted participants were tested under four conditions: with or without motion interruption by interframe mask, and with or without simulated low visual acuity (20/120 on average) by using a diffusing filter. Videos were down-sampled to 2.5 Hz, to allow the addition of motion interrupting masks between the frames to maintain video durations. In addition, single still frames extracted from the videos were shown in random order to eight normally sighted participants, who judged whether the frames were during ongoing hazards, with or without the diffuser. Sensitivity index d-prime (d{\textquoteright}) was compared between unmasked motion ( = 20) and still frame conditions ( = 8). Results: In the experiment using videos, there was a significant reduction in a combined performance score (taking account of reaction time and detection rate) when the motion was disrupted ( = 0.016). The diffuser did not affect the scores ( = 0.419). The score reduction was mostly due to a decrease in the detection rate ( = 0.002), not the response time ( = 0.148). The d{\textquoteright} of participants significantly decreased ( \&lt; 0.001) from 2.24 with unmasked videos to 0.68 with still frames. Low visual acuity also had a significant effect on the d{\textquoteright} ( = 0.004), but the change was relatively small, from 2.03 without to 1.56 with the diffuser. Conclusions: Motion perception plays a more important role than visual acuity for detecting driving hazards. Translational Relevance: Motion perception may be a relevant criterion for fitness to drive.},
	issn = {2164-2591},
	doi = {10.1167/tvst.9.13.18},
	author = {Moharrer, Mojtaba and Tang, Xiaolan and Luo, Gang}
}
@article {1528413,
	title = {Autistic-Like Features in Visually Impaired Children: A Review of Literature and Directions for Future Research},
	journal = {Brain Sci},
	volume = {10},
	number = {8},
	year = {2020},
	month = {2020 Aug 01},
	abstract = {There remains great interest in understanding the relationship between visual impairment (VI) and autism spectrum disorder (ASD) due to the extraordinarily high prevalence of ASD in blind and visually impaired children. The broad variability across individuals and assessment methodologies have made it difficult to understand whether autistic-like symptoms shown by some children with VI might reflect the influence of the visual deficit, or represent a primary neurodevelopmental condition that occurs independently of the VI itself. In the absence of a valid methodology adapted for the visually impaired population, diagnosis of ASD in children with VI is often based on non-objective clinical impression, with inconclusive prevalence data. In this review, we discuss the current state of knowledge and suggest directions for future research.},
	issn = {2076-3425},
	doi = {10.3390/brainsci10080507},
	author = {Molinaro, Anna and Micheletti, Serena and Rossi, Andrea and Gitti, Filippo and Galli, Jessica and Merabet, Lotfi B and Fazzi, Elisa Maria}
}
@article {1439857,
	title = {Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition},
	journal = {J Tissue Eng Regen Med},
	volume = {13},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {1528-1543},
	abstract = {Activated T cells are known to promote fibrosis, a major complication limiting the range of polymeric hydrogels as artificial corneal implants. As T cells are activated by dendritic cells (DC), minimally activating hydrogels would be optimal. In this study, we evaluated the ability of a series of engineered (manufactured/fabricated) and natural collagen matrices to either activate DC or conversely induce DC apoptosis in vitro. Bone marrow DC were cultured on a series of singly and doubly crosslinked hydrogels (made from recombinant human collagen III [RHCIII] or collagen mimetic peptide [CMP]) or on natural collagen-containing matrices, Matrigel and de-cellularised mouse corneal stroma. DC surface expression of major histocompatibility complex Class II and CD86 as well as apoptosis markers were examined. Natural matrices induced low levels of DC activation and maintained a "tolerogenic" phenotype. The same applied to singly crosslinked CMP-PEG gels. RHCIII gels singly crosslinked using either N-(3-dimethylaminopropyl)-N{\textquoteright}-ethylcarbodiimide with the coinitiator N-hydroxy succinimide (EDC-NHS) or N-cyclohexyl-N-(2-morpholinoethyl)carbodiimide metho-p-toulenesulfonate with NHS (CMC-NHS) induced varying levels of DC activation. In contrast, however, RHCIII hydrogels incorporating an additional polymeric network of 2-methacryloyloxyethyl phosphorylcholine did not activate DC but instead induced DC apoptosis, a phenomenon observed in natural matrices. This correlated with increased DC expression of leukocyte-associated immunoglobulin-like receptor-1. Despite low immunogenic potential, viable tolerogenic DC migrated into and through both natural and manufactured RHCIII gels. These data show that the immunogenic potential of RHCIII gels varies with the nature and composition of the gel. Preclinical evaluation of hydrogel immunogenic/fibrogenic potential is recommended.},
	issn = {1932-7005},
	doi = {10.1002/term.2903},
	author = {M{\"o}lzer, Christine and Shankar, Sucharita P and Griffith, May and Islam, M Mirazul and Forrester, John V and Kuffov{\'a}, Lucia}
}
@article {1109856,
	title = {Consensus on Diagnostic Criteria of Idiopathic Orbital Inflammation Using a Modified Delphi Approach},
	journal = {JAMA Ophthalmol},
	year = {2017},
	month = {2017 Jun 01},
	abstract = {Importance: Current practice to diagnose idiopathic orbital inflammation (IOI) is inconsistent, leading to frequent misdiagnosis of other orbital entities, including cancer. By specifying criteria, diagnosis of orbital inflammation will be improved. Objective: To define a set of criteria specific for the diagnosis of IOI. Design, Setting, and Participants: A 3-round modified Delphi process with an expert panel was conducted from June 8, 2015, to January 25, 2016. Fifty-three orbital scientist experts, identified through membership in the Orbital Society, were invited to participate in on online survey and they scored, using 5-point Likert scales, items that are eligible as diagnostic criteria from the literature and from personal experience. The items were clustered around the anatomic subtypes of IOI: idiopathic dacryoadenitis and idiopathic orbital fat inflammation (2 nonmyositic IOIs), and idiopathic orbital myositis (myositic IOI). Items with dissensus were rescored in the second round, and all items with consensus (median, >=4; interquartile range, <=1) were ranked by importance in the third round. Main Outcomes and Measures: Consensus on items to be included in the criteria. Results: Of the 53 experts invited to participate, a multinational panel of 35 (66\%) individuals with a mean (SD) years of experience of 31 (11) years were included. Consensus was achieved on 7 of 14 clinical and radiologic items and 5 of 7 pathologic items related to diagnosis of nonmyositic IOI, and 11 of 14 clinical and radiologic items and 1 of 5 pathologic items for myositic IOI. There was agreement among panelists to focus on surgical tissue biopsy results in the diagnosis of nonmyositic IOI and on a trial with systemic corticosteroids in myositic IOI. Panelists agreed that a maximum number of 30 IgG4-positive plasma cells per high-power field in the orbital tissue is compatible with the diagnosis of IOI. Conclusions and Relevance: An international panel of experts endorsed consensus diagnostic criteria of IOI. These criteria define a level of exclusion suggested for diagnosis and include tissue biopsy for lesions not confined to the extraocular muscles. This consensus is a step toward developing guidelines for the management of IOI, which needs to be followed by validation studies of the criteria.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.1581},
	author = {Mombaerts, Ilse and Bilyk, Jurij R and Rose, Geoffrey E and McNab, Alan A and Fay, Aaron and Peter J Dolman and Allen, Richard C and Devoto, Martin H and Harris, Gerald J and Expert Panel of the Orbital Society}
}
@article {1333945,
	title = {Molecular layer deposition builds biocompatible substrates for epithelial cells},
	journal = {J Biomed Mater Res A},
	volume = {106},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {3090-3098},
	abstract = {The demand for novel biocompatible materials as surface coating in the field of regenerative medicine is high. We explored molecular layer deposition (MLD) technique for building surface coatings and introduced a new group of substrates consisting of amino acids, or nucleobases, and the biocompatible metal titanium. The substrates were built from titanium tetraisopropoxide (TTIP) with l-lysine, glycine, l-aspartic acid, l-arginine, thymine, uracil, and adenine. Substrates based on zirconium chloride and terephthalic acid were also included. Titanium oxide (TiO ) substrates made by atomic layer deposition and uncoated cover slips served as controls. Rat conjunctival epithelial goblet cells were grown in RPMI 1640 and RT-PCR, immunofluorescence, cell attachment, proliferation, and viability were analyzed. Cells cultured on MLD and uncoated substrates were proliferating (positive for Ki67). Cell attachment after 3 h of culture on MLD substrates was similar to uncoated coverslips (p \&gt; 0.05). Compared to uncoated coverslips, cell proliferation assayed with alamarBlue{\textregistered} after 4 days was significantly higher on all MLD substrates (p \&lt; 0.05), whereas terephthalic acid-containing MLD substrates reduced proliferation (p \&lt; 0.01). Viability assessed by LIVE/DEAD{\textregistered} was high (\&gt;85\%) for all substrates after 5 days. The novel MLD technique is promising for building biocompatible substrates that direct epithelial cell growth. {\textcopyright} 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3090-3098, 2018.},
	issn = {1552-4965},
	doi = {10.1002/jbm.a.36499},
	author = {Momtazi, Leva and Dartt, Darlene A. and Nilsen, Ola and Eidet, Jon Roger}
}
@article {1748476,
	title = {Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye},
	journal = {Proc Natl Acad Sci U S A},
	volume = {120},
	number = {34},
	year = {2023},
	month = {2023 Aug 22},
	pages = {e2306153120},
	abstract = {Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here, we used high-throughput single-nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in six extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases-for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ~151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the data presented here complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of \&gt;180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as the neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.},
	keywords = {Endothelial Cells, Glaucoma, Humans, Optic Disk, Optic Nerve, Sclera, Transcriptome},
	issn = {1091-6490},
	doi = {10.1073/pnas.2306153120},
	author = {Monavarfeshani, Aboozar and Yan, Wenjun and Pappas, Christian and Odenigbo, Kenechukwu A and He, Zhigang and Segr{\`e}, Ayellet V and van Zyl, Tav{\'e} and Hageman, Gregory S and Sanes, Joshua R}
}
@article {1549020,
	title = {Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER},
	journal = {Ophthalmology},
	volume = {128},
	number = {7},
	year = {2021},
	month = {2021 Jul},
	pages = {1050-1059},
	abstract = {PURPOSE: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328). PARTICIPANTS: Patients (N\&nbsp;= 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes). METHODS: The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by >=2 readers, then adjudicated by the SRC as a group. MAIN OUTCOME MEASURES: Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset. RESULTS: Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6\% (IOI\&nbsp;+ vasculitis, 3.3\%; IOI\&nbsp;+ vasculitis\&nbsp;+ occlusion, 2.1\%). There were 8 cases (incidence 0.74\%) of at least moderate visual acuity loss (>=15 ETDRS letters) in eyes with IOI (7 in eyes with IOI\&nbsp;+ vasculitis\&nbsp;+ occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1\%, with at least moderate visual acuity loss in 0.14\%. CONCLUSIONS: This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.11.011},
	author = {Mon{\'e}s, Jordi and Srivastava, Sunil K and Jaffe, Glenn J and Tadayoni, Ramin and Albini, Thomas A and Kaiser, Peter K and Holz, Frank G and Korobelnik, Jean-Francois and Kim, Ivana K and Pruente, Christian and Murray, Timothy G and Heier, Jeffrey S}
}
@article {1608602,
	title = {Wide-field swept-source optical coherence tomography angiography in the assessment of retinal microvasculature and choroidal thickness in patients with myopia},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {102-108},
	abstract = {BACKGROUND/AIMS: Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). METHODS: This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. RESULTS: This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12{\texttimes}12 mm{\texttwosuperior} scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (βVD=-0.39, βVSD=-10.25, p\&lt;0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. CONCLUSION: Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.},
	keywords = {Cross-Sectional Studies, Fluorescein Angiography, Humans, Microvessels, Myopia, Prospective Studies, Retina, Retinal Vessels, Tomography, Optical Coherence},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-319540},
	author = {Moon, Jade Y and Garg, Itika and Cui, Ying and Katz, Raviv and Zhu, Ying and Le, Rongrong and Lu, Yifan and Lu, Edward S and Ludwig, Cassie A and Tobias Elze and Wu, David M and Eliott, Dean and Miller, Joan W and Kim, Leo A and Husain, Deeba and Vavvas, Demetrios G and Miller, John B}
}
@article {1559542,
	title = {The Impact of the COVID-19 Pandemic on Ophthalmic Care at an Eye-Specific Emergency Department in an Outbreak Hotspot},
	journal = {Clin Ophthalmol},
	volume = {14},
	year = {2020},
	month = {2020},
	pages = {4155-4163},
	abstract = {Purpose: During the COVID-19 pandemic, there is growing concern that patients are forgoing necessary care. Emergency departments (ED) represent an important site of eye care. We analyzed patterns of ED visits at an eye-specific ED since the declaration of the public health crisis. Materials and Methods: In this retrospective, cross-sectional single center study, medical records of 6744 patients who presented to the Massachusetts Eye and Ear ED between March 1st and April 30th in 2018, 2019, and 2020 were studied. The primary outcome measures were total volume of ED visits, proportion of urgent ED visits, and proportion of surgical visits. Results: Overall, the median number of daily visits to the ED decreased by 18 visits per day since the declaration of public health guidelines (interquartile range, 9-24, p \&lt; 0.001). This accounted for a 32\% decrease in the total volume of ED visits in 2020 compared to prior years during the study period (p \&lt; 0.001). There was a 9\% increase in the proportion of primary diagnoses considered urgent (p = 0.002). The proportion of visits requiring urgent surgery increased by 39\% (p = 0.004). Conclusion: The total number of eye-specific ED visits dropped compared to prior years while the proportion of urgent visits increased. Patients were likely more reluctant to seek eye care, deferring less urgent evaluation.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S285223},
	author = {Moon, Jade Y and Miller, John B and Katz, Raviv and Ta, Thong and Szypko, Colleen and Garg, Itika and Lorch, Alice C and Gardiner, Matthew F and Armstrong, Grayson W}
}
@article {1658684,
	title = {Visualization of retinal breaks on ultra-widefield fundus imaging using a digital green filter},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {261},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {935-940},
	abstract = {PURPOSE: We compare the ability of resident physicians to identify retinal breaks on ultra-widefield color fundus photos using the traditional image compared to an image with a green filter overlay. METHODS: Residents were shown fundus photos of 10 eyes with either a retinal tear or hole. Participants were shown each photo twice-once with traditional color settings and once with a green filter overlay. Participants were scored on whether the break was correctly identified and timed on how long it took to identify the pathology. RESULTS: Residents were able to correctly identify more retinal breaks on fundus photos with a green filter overlay compared to photos with traditional settings (P = 0.02). Residents were also able to identify breaks on fundus photos more quickly on images with a green filter overlay compared to the traditional images (P \&lt; 0.001). CONCLUSIONS: The application of a green filter overlay may help in identifying retinal breaks.},
	keywords = {Fluorescein Angiography, Fundus Oculi, Humans, Retinal Perforations, Tomography, Optical Coherence},
	issn = {1435-702X},
	doi = {10.1007/s00417-022-05855-8},
	author = {Moon, Jade Y and Wai, Karen M and Patel, Neal S and Katz, Raviv and Dahrouj, Mohammad and Miller, John B}
}
@article {1647883,
	title = {Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury},
	journal = {Biochem Pharmacol},
	volume = {203},
	year = {2022},
	month = {2022 09},
	pages = {115168},
	abstract = {Pathological deterioration of mitochondrial function is increasingly linked with multiple degenerative illnesses as a mediator of a wide range of neurologic and age-related chronic diseases, including those of genetic origin. Several of these diseases are rare, typically defined in the United States as an illness affecting fewer than 200,000 people in the U.S. population, or about one in 1600 individuals. Vision impairment due to mitochondrial dysfunction in the eye is a prominent feature evident in numerous primary mitochondrial diseases and is common to the pathophysiology of many of the familiar ophthalmic disorders, including age-related macular degeneration, diabetic retinopathy, glaucoma and retinopathy of prematurity - a collection of syndromes, diseases and disorders with significant unmet medical needs. Focusing on metabolic mitochondrial pathway mechanisms, including the possible roles of cuproptosis and ferroptosis in retinal mitochondrial dysfunction, we shed light on the potential of α-lipoyl-L-carnitine in treating eye diseases. α-Lipoyl-L-carnitine is a bioavailable mitochondria-targeting lipoic acid prodrug that has shown potential in protecting against retinal degeneration and photoreceptor cell loss in ophthalmic indications.},
	keywords = {Carnitine, Humans, Infant, Newborn, Mitochondria, Photoreceptor Cells, Retina, Retinal Degeneration},
	issn = {1873-2968},
	doi = {10.1016/j.bcp.2022.115168},
	author = {Moos, Walter H and Faller, Douglas V and Glavas, Ioannis P and Harpp, David N and Kamperi, Natalia and Kanara, Iphigenia and Kodukula, Krishna and Mavrakis, Anastasios N and Pernokas, Julie and Pernokas, Mark and Pinkert, Carl A and Powers, Whitney R and Sampani, Konstantina and Steliou, Kosta and Tamvakopoulos, Constantin and Vavvas, Demetrios G and Zamboni, Robert J and Chen, XiaoHong}
}
@article {1619408,
	title = {Pathogenic mitochondrial dysfunction and metabolic abnormalities},
	journal = {Biochem Pharmacol},
	volume = {193},
	year = {2021},
	month = {2021 11},
	pages = {114809},
	abstract = {Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular microorganisms including bacteria and viruses are primary pathogenic drivers that cause disease. Missing from this statement are subcellular compartments, importantly mitochondria, which can be pathogenic by themselves, also serving as key metabolic disease intermediaries. The breakdown of food molecules provides chemical energy to power cellular processes, with mitochondria as powerhouses and ATP as the principal energy carrying molecule. Most animal cell ATP is produced by mitochondrial synthase; its central role in metabolism has been known for\&nbsp;\&gt;80\&nbsp;years. Metabolic disorders involving many organ systems are prevalent in all age groups. Progressive pathogenic mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases, the most common phenotypic expression of inherited metabolic disorders. Confluent genetic, metabolic, and mitochondrial axes surface in diabetes, heart failure, neurodegenerative disease, and even in the ongoing coronavirus pandemic.},
	keywords = {Animals, COVID-19, Diet, Healthy, Energy Metabolism, Humans, Metabolic Diseases, Mitochondria, Mitochondrial Diseases, Neurodegenerative Diseases, Oxidative Stress},
	issn = {1873-2968},
	doi = {10.1016/j.bcp.2021.114809},
	author = {Moos, Walter H and Faller, Douglas V and Glavas, Ioannis P and Harpp, David N and Kamperi, Natalia and Kanara, Iphigenia and Kodukula, Krishna and Mavrakis, Anastasios N and Pernokas, Julie and Pernokas, Mark and Pinkert, Carl A and Powers, Whitney R and Steliou, Kosta and Tamvakopoulos, Constantin and Vavvas, Demetrios G and Zamboni, Robert J and Sampani, Konstantina}
}
@article {1323935,
	title = {A New Approach to Treating Neurodegenerative Otologic Disorders},
	journal = {Biores Open Access},
	volume = {7},
	number = {1},
	year = {2018},
	month = {2018},
	pages = {107-115},
	abstract = {Hearing loss, the most common neurological disorder and the fourth leading cause of years lived with disability, can have profound effects on quality of life. The impact of this "invisible disability," with significant consequences, economic and personal, is most substantial in low- and middle-income countries, where \&gt;80\% of affected people live. Given the importance of hearing for communication, enjoyment, and safety, with up to 500 million affected globally at a cost of nearly $800 billion/year, research on new approaches toward prevention and treatment is attracting increased attention. The consequences of noise pollution are largely preventable, but irreversible hearing loss can result from aging, disease, or drug side effects. Once damage occurs, treatment relies on hearing aids and cochlear implants. Preventing, delaying, or reducing some degree of hearing loss may be possible by avoiding excessive noise and addressing major contributory factors such as cardiovascular risk. However, given the magnitude of the problem, these interventions alone are unlikely to be sufficient. Recent advances in understanding principal mechanisms that govern hearing function, together with new drug discovery paradigms designed to identify efficacious therapies, bode well for pharmaceutical intervention. This review surveys various causes of loss of auditory function and discusses potential neurological underpinnings, including mitochondrial dysfunction. Mitochondria mitigate cell protection, survival, and function and may succumb to cumulative degradation of energy production and performance; the end result is cell death. Energy-demanding neurons and vestibulocochlear hair cells are vulnerable to mitochondrial dysfunction, and hearing impairment and deafness are characteristic of neurodegenerative mitochondrial disease phenotypes. Beyond acting as cellular powerhouses, mitochondria regulate immune responses to infections, and studies of this phenomenon have aided in identifying nuclear factor kappa B and nuclear factor erythroid 2-related factor 2/antioxidant response element signaling as targets for discovery of otologic drugs, respectively, suppressing or upregulating these pathways. Treatment with free radical scavenging antioxidants is one therapeutic approach, with lipoic acid and corresponding carnitine esters exhibiting improved biodistribution and other features showing promise. These compounds are also histone deacetylase (HDAC) inhibitors, adding epigenetic modulation to the mechanistic milieu through which they act. These data suggest that new drugs targeting mitochondrial dysfunction and modulating epigenetic pathways via HDAC inhibition or other mechanisms hold great promise.},
	issn = {2164-7844},
	doi = {10.1089/biores.2018.0017},
	author = {Moos, Walter H and Faller, Douglas V and Glavas, Ioannis P and Harpp, David N and Irwin, Michael H and Kanara, Iphigenia and Pinkert, Carl A and Powers, Whitney R and Steliou, Kosta and Vavvas, Demetrios G and Kodukula, Krishna}
}
@article {1748386,
	title = {Epilepsy: Mitochondrial connections to the {\textquoteright}Sacred{\textquoteright} disease},
	journal = {Mitochondrion},
	volume = {72},
	year = {2023},
	month = {2023 Sep},
	pages = {84-101},
	abstract = {Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging. Diagnosis and monitoring of childhood epilepsy add to the need for non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms of epileptogenesis are not fully understood, evidence for mitochondrial involvement is substantial. Seizures affect 35\%-60\% of patients diagnosed with mitochondrial diseases. Mitochondrial dysfunction is pathophysiological in various epilepsies, including those of non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads to altered neuronal bioenergetics, metabolism and neurological complications, including seizures. Iron-dependent lipid peroxidation initiates ferroptosis, a cell death pathway that aligns with altered mitochondrial bioenergetics, metabolism and morphology found in neurodegenerative diseases (NDDs). Studies in mouse genetic models with seizure phenotypes where the function of an essential selenoprotein (GPX4) is targeted suggest roles for ferroptosis in epilepsy. GPX4 is pivotal in NDDs, where selenium protects interneurons from ferroptosis. Selenium is an essential central nervous system micronutrient and trace element. Low serum concentrations of selenium and other trace elements and minerals, including iron, are noted in diagnosing childhood epilepsy. Selenium supplements alleviate intractable seizures in children with reduced GPX activity. Copper and cuproptosis, like iron and ferroptosis, link to mitochondria and NDDs. Connecting these mechanistic pathways to selenoproteins provides new insights into treating seizures, pointing to using medicines including prodrugs of lipoic acid to treat epilepsy and to potential alternative therapeutic approaches including transcranial magnetic stimulation (transcranial), photobiomodulation and vagus nerve stimulation.},
	keywords = {Animals, Epilepsy, Iron, Mice, Mitochondria, Seizures, Selenium},
	issn = {1872-8278},
	doi = {10.1016/j.mito.2023.08.002},
	author = {Moos, Walter H and Faller, Douglas V and Glavas, Ioannis P and Kanara, Iphigenia and Kodukula, Krishna and Pernokas, Julie and Pernokas, Mark and Pinkert, Carl A and Powers, Whitney R and Sampani, Konstantina and Steliou, Kosta and Vavvas, Demetrios G}
}
@article {913506,
	title = {Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications.},
	journal = {Am J Physiol Heart Circ Physiol},
	volume = {311},
	number = {3},
	year = {2016},
	month = {2016 Sep 1},
	pages = {H738-49},
	abstract = {Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications.},
	issn = {1522-1539},
	doi = {10.1152/ajpheart.00005.2016},
	author = {Moran, Elizabeth P and Wang, Zhongxiao and Chen, Jing and Sapieha, Przemyslaw and Smith, Lois E H and Ma, Jian-Xing}
}
@article {541231,
	title = {Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.},
	journal = {PLoS One},
	volume = {10},
	number = {9},
	year = {2015},
	month = {2015},
	pages = {e0135927},
	abstract = {Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T\&gt;C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C\&gt;T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0135927},
	author = {Moreno-Ramos, Oscar A and Olivares, Ana Mar{\'\i}a and Haider, Neena B and de Autismo, Liga Colombiana and Lattig, Mar{\'\i}a Claudia}
}
@article {1559576,
	title = {Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening},
	journal = {Bone Marrow Transplant},
	volume = {56},
	number = {6},
	year = {2021},
	month = {2021 06},
	pages = {1266-1271},
	abstract = {Although cytomegalovirus (CMV) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), the incidence of CMV retinitis is considered to be lower than the incidence of CMV infection in other organs following allogeneic HSCT. In this study, the incidence and characteristics of CMV retinitis were retrospectively evaluated in recipients of allogeneic HSCT. Ophthalmological screening was performed at the development of ocular symptoms or positive CMV infection using peripheral blood evaluated by pp65 antigenemia or polymerase chain reaction. Of the 514 patients, 13 patients developed CMV retinitis. The median onset of CMV retinitis was day 34 (range, 21-118) post transplant, and the cumulative incidence was 2.5\% (95\% CI, 1.6-4.2) at 6 months after transplantation. Five patients presented ocular symptoms at the onset. In the remaining eight asymptomatic patients, the diagnosis of CMV retinitis was made by the screening guided by positive CMV infection. All evaluable patients responded to antiviral treatment but three showed incomplete improvement with ocular sequela. Our results suggest that the incidence of CMV retinitis after allogeneic HSCT is not negligible and active ophthalmological screening based not only on symptoms but also positive CMV infection monitoring contributes to the early diagnosis of CMV retinitis.},
	keywords = {Antiviral Agents, Cytomegalovirus, Cytomegalovirus Retinitis, Hematopoietic Stem Cell Transplantation, Humans, Retrospective Studies},
	issn = {1476-5365},
	doi = {10.1038/s41409-020-01176-8},
	author = {Mori, Takehiko and Kikuchi, Taku and Koh, Miki and Koda, Yuya and Yamazaki, Rie and Sakurai, Masatoshi and Tomita, Yohei and Ozawa, Yoko and Kohashi, Sumiko and Abe, Ryohei and Saburi, Masuho and Kato, Jun}
}
@article {1653579,
	title = {Computer clinical decision support that automates personalized clinical care: a challenging but needed healthcare delivery strategy},
	journal = {J Am Med Inform Assoc},
	volume = {30},
	number = {1},
	year = {2022},
	month = {2022 Dec 13},
	pages = {178-194},
	abstract = {How to deliver best care in various clinical settings remains a vexing problem. All pertinent healthcare-related questions have not, cannot, and will not be addressable with costly time- and resource-consuming controlled clinical trials. At present, evidence-based guidelines can address only a small fraction of the types of care that clinicians deliver. Furthermore, underserved areas rarely can access state-of-the-art evidence-based guidelines in real-time, and often lack the wherewithal to implement advanced guidelines. Care providers in such settings frequently do not have sufficient training to undertake advanced guideline implementation. Nevertheless, in advanced modern healthcare delivery environments, use of eActions (validated clinical decision support systems) could help overcome the cognitive limitations of overburdened clinicians. Widespread use of eActions will require surmounting current healthcare technical and cultural barriers and installing clinical evidence/data curation systems. The authors expect that increased numbers of evidence-based guidelines will result from future comparative effectiveness clinical research carried out during routine healthcare delivery within learning healthcare systems.},
	keywords = {Computers, Decision Support Systems, Clinical, Delivery of Health Care},
	issn = {1527-974X},
	doi = {10.1093/jamia/ocac143},
	author = {Morris, Alan H and Horvat, Christopher and Stagg, Brian and Grainger, David W and Lanspa, Michael and Orme, James and Clemmer, Terry P and Weaver, Lindell K and Thomas, Frank O and Grissom, Colin K and Hirshberg, Ellie and East, Thomas D and Wallace, Carrie Jane and Young, Michael P and Sittig, Dean F and Suchyta, Mary and Pearl, James E and Pesenti, Antinio and Bombino, Michela and Beck, Eduardo and Sward, Katherine A and Weir, Charlene and Phansalkar, Shobha and Bernard, Gordon R and Thompson, B Taylor and Brower, Roy and Truwit, Jonathon and Steingrub, Jay and Hiten, R Duncan and Willson, Douglas F and Zimmerman, Jerry J and Nadkarni, Vinay and Randolph, Adrienne G and Curley, Martha A Q and Newth, Christopher J L and Lacroix, Jacques and Agus, Michael S D and Lee, Kang Hoe and deBoisblanc, Bennett P and Moore, Frederick Alan and Evans, R Scott and Sorenson, Dean K and Wong, Anthony and Boland, Michael V and Dere, Willard H and Crandall, Alan and Facelli, Julio and Huff, Stanley M and Haug, Peter J and Pielmeier, Ulrike and Rees, Stephen E and Karbing, Dan S and Andreassen, Steen and Fan, Eddy and Goldring, Roberta M and Berger, Kenneth I and Oppenheimer, Beno W and Ely, E Wesley and Pickering, Brian W and Schoenfeld, David A and Tocino, Irena and Gonnering, Russell S and Pronovost, Peter J and Savitz, Lucy A and Dreyfuss, Didier and Slutsky, Arthur S and Crapo, James D and Pinsky, Michael R and James, Brent and Berwick, Donald M}
}
@article {1559537,
	title = {Office- or Facility-Based Probing for Congenital Nasolacrimal Duct Obstruction: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {128},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {920-927},
	abstract = {PURPOSE: To review the published literature assessing the efficacy and safety of in-office probing compared with facility-based probing to treat congenital nasolacrimal duct obstruction (NLDO). METHODS: Literature searches were conducted in March 2020 in the PubMed database with no date restrictions and limited to studies published in English and in the Cochrane Library database with no restrictions. The combined searches yielded 281 citations. Of these, 21 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. Four articles were rated level I, 2 articles were rated level II, and 15 articles were rated level III. RESULTS: Treatments consisted of observation, in-office nasolacrimal probing, or facility-based nasolacrimal probing. Success rates and complications or recurrences were recorded from 1 week to 6 months after surgery. Complete resolution of symptoms after surgery ranged from 66\% to 95.6\% for office-based procedures versus 50\% to 97.7\% for facility-based procedures. Level I evidence indicated that 66\% of cases spontaneously resolved after 6 months of observation in infants between 6 and 10 months of age. Success rates for in-office probing were lower for bilateral than for unilateral NLDO (67\% vs. 82\%), whereas success rates were high in both unilateral (83\%) and bilateral (82\%) patients who underwent facility-based probing after 6 months of observation. Cost data did not indicate a definitive cost savings of either treatment method ($562 for in-office vs. $701 for facility-based, depending on cost models predicting spontaneous resolution rates at different ages). No serious adverse events with treatment or anesthesia were reported for either treatment method. CONCLUSIONS: Evidence supports the efficacy and safety of both in-office and facility-based surgery for congenital NLDO. However, treating bilateral NLDO in a facility setting may be better. Because a significant percentage of children achieved resolution spontaneously before 12 months of age, deferring treatment until 12 to 18 months of age is a reasonable option. Additional research may address symptom burden on families and the impact of anesthesia and emotional trauma of nonsedated office probings on patients and may explore further the cost of treatment for each treatment method.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.10.028},
	author = {Morrison, David G and Binenbaum, Gil and Chang, Melinda Y and Heidary, Gena and Trivedi, Rupal H and Galvin, Jennifer A and Pineles, Stacy L}
}
@article {503946,
	title = {Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world.},
	journal = {Front Genet},
	volume = {6},
	year = {2015},
	month = {2015},
	pages = {238},
	abstract = {We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age \&gt; 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40\%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus.},
	issn = {1664-8021},
	doi = {10.3389/fgene.2015.00238},
	author = {Morrison, Margaux A and Magalhaes, Tiago R and Ramke, Jacqueline and Smith, Silvia E and Ennis, Sean and Simpson, Claire L and Portas, Laura and Murgia, Federico and Ahn, Jeeyun and Dardenne, Caitlin and Mayne, Katie and Robinson, Rosann and Morgan, Denise J and Brian, Garry and Lee, Lucy and Woo, Se J and Zacharaki, Fani and Tsironi, Evangelia E and Miller, Joan W and Kim, Ivana K and Park, Kyu H and Bailey-Wilson, Joan E and Farrer, Lindsay A and Stambolian, Dwight and Deangelis, Margaret M}
}
@article {1748506,
	title = {Levodopa/Carbidopa to Augment the Treatment of Amblyopia: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {130},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1221-1227},
	abstract = {PURPOSE: To review the published literature on the use of levodopa/carbidopa to augment the treatment of amblyopia. METHODS: Literature searches for English language studies were last conducted in October 2022 in the PubMed database with no date restrictions. The combined searches yielded 55 articles, of which 23 were reviewed in full text. Twelve of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. Nine studies were rated level I, and 3 studies were rated level II; there were no level III studies. RESULTS: The duration of treatment was limited to 3 to 16 weeks because of concern about long-term adverse effects such as tardive dyskinesia. This complication was not reported in any of the study participants. The dose of levodopa ranged from 1.5 to 8.3 mg/kg/day, generally divided into 3 daily doses. The carbidopa dose was approximately 25\% of the levodopa dose in all treatments. Evidence from these studies indicates that augmenting traditional patch occlusion therapy with the oral administration of levodopa/carbidopa can improve the vision of amblyopic children, but the effect was small (0.17-0.3 logarithm of the minimum angle of resolution [logMAR] units) and only statistically significant when compared with patching alone in 2 of the 12 studies cited. Regression of vision was reported in the majority of studies (9 of 12 reported; range, 0-0.17 logMAR unit regression) after discontinuation of therapy. Short-term side effects of the medications were not consistently reported but were most frequently mild and included headache and nausea. CONCLUSIONS: The best available evidence is currently insufficient to show that augmenting amblyopia therapy using up to 16 weeks of levodopa/carbidopa will result in meaningful improvement in visual acuity. Given the potential for significant side effects such as tardive dyskinesia with long-term therapy, levodopa/carbidopa does not appear to be a viable option for amblyopia therapy FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.07.008},
	author = {Morrison, David G and Heidary, Gena and Chang, Melinda Y and Binenbaum, Gil and Cavuoto, Kara M and Galvin, Jennifer and Trivedi, Rupal and Kim, Stephen J and Pineles, Stacy L}
}
@article {1635639,
	title = {Neurodevelopmental disorders and somatic diagnoses in a national cohort of children born before 24 weeks of gestation},
	journal = {Acta Paediatr},
	volume = {111},
	number = {6},
	year = {2022},
	month = {2022 Jun},
	pages = {1167-1175},
	abstract = {AIM: This study investigated childhood diagnoses in children born extremely preterm before 24\&nbsp;weeks of gestation. METHODS: Diagnoses of neurodevelopmental disorders and selected somatic diagnoses were retrospectively retrieved from national Swedish registries for children born before 24 weeks from 2007 to 2018. Their individual medical files were also examined. RESULTS: We studied 383 children born at a median of 23.3 (range 21.9-23.9) weeks, with a median birthweight of 565 (range 340-874) grams. Three-quarters (75\%) had neurodevelopmental disorders, including speech disorders (52\%), intellectual disabilities (40\%), attention deficit hyperactivity disorder (30\%), autism spectrum disorders (24\%), visual impairment (22\%), cerebral palsy (17\%), epilepsy (10\%) and hearing impairment (5\%). More boys than girls born at 23\&nbsp;weeks had intellectual disabilities (45\% vs. 27\%, p\&nbsp;\&lt;\&nbsp;0.01) and visual impairment (25\% vs. 14\%, p\&nbsp;\&lt;\&nbsp;0.01). Just over half of the cohort (55\%) received habilitation care. The majority (88\%) had somatic diagnoses, including asthma (63\%) and failure to thrive/short stature (39\%). CONCLUSION: Most children born before 24\&nbsp;weeks had neurodevelopmental disorders and/or additional somatic diagnoses in childhood and were referred to habilitation services. Clinicians should be aware of the multiple health and developmental problems affecting these children. Resources are needed to identify their long-term support needs at an early stage.},
	keywords = {Autism Spectrum Disorder, Child, Female, Humans, Infant, Newborn, intellectual disability, Male, Neurodevelopmental Disorders, Retrospective Studies, Vision Disorders},
	issn = {1651-2227},
	doi = {10.1111/apa.16316},
	author = {Morsing, Eva and Lundgren, Pia and H{\r a}rd, Anna-Lena and Rakow, Alexander and Hellstr{\"o}m-Westas, Lena and Jacobson, Lena and Johnson, Mats and Nilsson, Staffan and Smith, Lois E H and S{\"a}vman, Karin and Hellstr{\"o}m, Ann}
}
@article {1439856,
	title = {Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sj{\"o}gren Syndrome},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {6},
	year = {2019},
	month = {2019 May 01},
	pages = {2181-2197},
	abstract = {Purpose: Sj{\"o}gren syndrome is an autoimmune disorder that occurs almost exclusively in women and is associated with extensive inflammation in lacrimal tissue, an immune-mediated destruction and/or dysfunction of glandular epithelial cells, and a significant decrease in aqueous tear secretion. We discovered that androgens suppress the inflammation in, and enhance the function of, lacrimal glands in female mouse models (e.g., MRL/MpJ-Tnfrsf6lpr [MRL/lpr]) of Sj{\"o}gren syndrome. In contrast, others have reported that androgens induce an anomalous immunopathology in lacrimal glands of nonobese diabetic/LtJ (NOD) mice. We tested our hypothesis that these hormone actions reflect unique, strain- and tissue-specific effects, which involve significant changes in the expression of immune-related glandular genes. Methods: Lacrimal glands were obtained from age-matched, adult, female MRL/lpr and NOD mice after treatment with vehicle or testosterone for up to 3 weeks. Tissues were processed for analysis of differentially expressed mRNAs using CodeLink Bioarrays and Affymetrix GeneChips. Data were analyzed with bioinformatics and statistical software. Results: Testosterone significantly influenced the expression of numerous immune-related genes, ontologies, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in lacrimal glands of MRL/lpr and NOD mice. The nature of this hormone-induced immune response was dependent upon the autoimmune strain, and was not duplicated within lacrimal tissues of nonautoimmune BALB/c mice. The majority of immune-response genes regulated by testosterone were of the inflammatory type. Conclusions: Our findings support our hypothesis and indicate a major role for the lacrimal gland microenvironment in mediating androgen effects on immune gene expression.},
	issn = {1552-5783},
	doi = {10.1167/iovs.19-26815},
	author = {Morthen, Mathias Kaurstad and Tellefsen, Sara and Richards, Stephen M and Lieberman, Scott M and Rahimi Darabad, Raheleh and Kam, Wendy R and Sullivan, David A}
}
@article {1364518,
	title = {Electroretinographic (ERG) responses in pediatric patients using vigabatrin},
	journal = {Doc Ophthalmol},
	volume = {124},
	number = {3},
	year = {2012},
	month = {2012 Jun},
	pages = {197-209},
	abstract = {The antiepileptic drug vigabatrin is known to cause retinal and visual dysfunction, particularly visual field defects, in some patients. Electroretinography (ERG) is used in an attempt to identify adverse effects of vigabatrin (VGB) in patients who are not candidates for conventional perimetry. We report data from 114 pediatric patients taking VGB referred for clinical evaluation; median age at test was 22.9 (2.4 to 266.1) months, and median duration of VGB use was 9.7 (0.3 to 140.7) months. Twenty-seven of them were tested longitudinally (3 to 12 ERG tests). ERG responses to full-field stimuli were recorded in scotopic and photopic conditions, and results were compared to responses from healthy control subjects. We found that abnormalities of photoreceptor and post-receptor ERG responses are frequent in these young patients. The most frequently abnormal scotopic parameter was post-receptor sensitivity, log σ, derived from the b-wave stimulus-response function; the most frequently abnormal photopic parameter was the implicit time of the OFF response (d-wave) to a long (150 ms) flash. Abnormal 30-Hz flicker response amplitude, previously reported to be a predictor of visual field loss, occurred infrequently. For the group as a whole, none of the ERG parameters changed significantly with increasing duration of VGB use. Four of the 27 patients tested longitudinally showed systematic worsening of log σ with duration of VGB use. In a subset of patients who underwent perimetry (N = 39), there was no significant association of any ERG parameter with visual field defects. We cannot determine whether the ERG abnormalities we found were due solely to the effects of VGB. We caution against over-reliance on the ERG to monitor pediatric patients for VGB toxicity and recommend further development of a reliable test of peripheral vision to supplant ERG testing.},
	keywords = {Adolescent, Adult, Anticonvulsants, Child, Child, Preschool, Electroretinography, Humans, Infant, Middle Aged, Nervous System Diseases, Retinal Cone Photoreceptor Cells, Retinal Diseases, Retinal Rod Photoreceptor Cells, Vigabatrin, Visual Acuity, Visual Fields, Young Adult},
	issn = {1573-2622},
	doi = {10.1007/s10633-012-9320-7},
	author = {Moskowitz, Anne and Hansen, Ronald M and Eklund, Susan E and Fulton, Anne B}
}
@article {1351171,
	title = {Inclusion of CD80 in HSV targets the recombinant virus to PD-L1 on DCs and allows productive infection and robust immune responses},
	journal = {PLoS One},
	volume = {9},
	number = {1},
	year = {2014},
	month = {2014},
	pages = {e87617},
	abstract = {CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC.},
	keywords = {Adjuvants, Immunologic, Animals, B7-1 Antigen, B7-H1 Antigen, Blotting, Southern, Dendritic Cells, DNA Primers, Flow Cytometry, Fluorescent Antibody Technique, Genetic Engineering, Herpes Simplex, Herpesvirus 1, Human, MicroRNAs, Rabbits, Real-Time Polymerase Chain Reaction, Recombination, Genetic, Viral Vaccines},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0087617},
	author = {Mott, Kevin R and Allen, Sariah J and Zandian, Mandana and Akbari, Omid and Hamrah, Pedram and Maazi, Hadi and Wechsler, Steven L and Sharpe, Arlene H and Freeman, Gordon J and Ghiasi, Homayon}
}
@article {1474203,
	title = {C-Fiber Assays in the Cornea vs. Skin},
	journal = {Brain Sci},
	volume = {9},
	number = {11},
	year = {2019},
	month = {2019 Nov 12},
	abstract = {C-fibers are unmyelinated nerve fibers that transmit high threshold mechanical, thermal, and chemical signals that are associated with pain sensations. This review examines current literature on measuring altered peripheral nerve morphology and discusses the most relevant aspects of corneal microscopy, especially whether corneal imaging presents significant method advantages over skin biopsy. Given its relative merits, corneal confocal microscopy would seem to be a more practical and patient-centric approach than utilizing skin biopsies.},
	issn = {2076-3425},
	doi = {10.3390/brainsci9110320},
	author = {Moulton, Eric A and Borsook, David}
}
@article {1732631,
	title = {Is blue light a red herring in a rodent model of "computer vision syndrome"?},
	journal = {Pain},
	volume = {164},
	number = {7},
	year = {2023},
	month = {2023 Jul 01},
	pages = {1640},
	keywords = {Animals, Asthenopia, Computers, Disease Models, Animal, Light, Rodentia},
	issn = {1872-6623},
	doi = {10.1097/j.pain.0000000000002941},
	author = {Moulton, Eric A and Galor, Anat and Ciolino, Joseph B and Jacobs, Deborah S}
}
@article {1309947,
	title = {Blurry Vision and Eye Pain After Pterygium Surgery},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {7},
	year = {2018},
	month = {2018 Jul 01},
	pages = {827-828},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.6054},
	author = {Moussa, Kareem and Shantha, Jessica and Schallhorn, Julie M}
}
@article {1360113,
	title = {Middle-Aged Man With Bilateral Subretinal Fluid},
	journal = {JAMA Ophthalmol},
	year = {2018},
	month = {2018 Nov 08},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.2759},
	author = {Moussa, Kareem and Bradbury, Michael and Wu, David M}
}
@article {1653606,
	title = {Systemic lymphoma masquerading as Vogt-Koyanagi-Harada syndrome: Report of a case with multimodal imaging and histopathology},
	journal = {Am J Ophthalmol Case Rep},
	volume = {27},
	year = {2022},
	month = {2022 Sep},
	pages = {101643},
	abstract = {Purpose: To report a case of systemic diffuse large B cell lymphoma presenting with ocular manifestations and neurologic findings resembling Vogt-Koyanagi-Harada syndrome. Observations: A 51-year-old Caucasian man presented with headache, ear pain, and blurry vision in both eyes. He was found to have bilateral exudative retinal detachments. After a short period of initial improvement with high dose systemic corticosteroid, his condition significantly worsened. An extensive work-up, including a kidney biopsy, led to a diagnosis of systemic diffuse large B cell lymphoma. He had excellent recovery following treatment with appropriate chemotherapy. Conclusions and Importance: Systemic malignancy may present with ocular manifestations and may masquerade as another diagnosis. An unexpected clinical course may suggest an alternative diagnosis. A broad systemic work-up including an evaluation for malignancy should be considered for patients presenting with unexplained exam or systemic findings.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101643},
	author = {Moussa, Kareem and Begaj, Tedi and Ma, Kevin and Barrantes, Paula Cortes and Eliott, Dean and Sobrin, Lucia}
}
@article {1647882,
	title = {Efficacy of Preoperative Risk Stratification on Resident Phacoemulsification Surgeries},
	journal = {Clin Ophthalmol},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {2137-2144},
	abstract = {Purpose: To evaluate efficacy of a novel risk stratification system in minimizing resident surgical complications\&nbsp;and to evaluate whether the system could be used to safely introduce cataract surgery to earlier levels of training. Materials and Methods: This is a retrospective cross-sectional study on 530 non-consecutive cataract cases performed by residents at Columbia University. Risk scores, preoperative best corrected visual acuity (BCVA), intraoperative complications, postoperative day 1 (POD1), and month 1 (POM1) exam findings were tabulated. The relationship between risk scores and POD1 and POM1 BCVA was modeled using linear regression. The relationship between risk scores and complication rates was modeled using logistic regression. Logistic regression was used to model the rates of complications across different levels of training. Rates of complications were compared between diabetic versus non-diabetic patients using t-tests. Results: Risk scores did not have significant association with intraoperative complications. Risk scores were predictive of corneal edema (OR = 1.36, p = 0.0032) and having any POM1 complication (OR = 1.20, p = 0.034). Risk scores were predictive of POD1 (β = 0.13, p \&lt; 0.0001) and POM1 (β = 0.057, p = 0.00048) visual acuity. There was no significant association between level of training and rates of intraoperative (p = 0.9) or postoperative complications (p = 0.06). Rates of intraoperative complication trended higher among diabetic patients but was not statistically significant (p = 0.2). Conclusion: Higher risk scores were predictive of prolonged corneal edema but not risk of intraoperative complications. Our risk stratification system allowed us to safely introduce earlier phacoemulsification surgery.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S368633},
	author = {Moussa, Omar and Frank, Tahvi and Valenzuela, Ives A and Aliancy, Joah and Gong, Dan and De Rojas, Joaquin O and Dagi Glass, Lora R and Winn, Bryan J and Cioffi, George A and Chen, Royce W S}
}
@article {1360114,
	title = {Retinal Exudates and Hemorrhages in a Survivor of Breast Cancer},
	journal = {JAMA Ophthalmol},
	year = {2018},
	month = {2018 Nov 29},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.3794},
	author = {Moussa, Kareem and Kim, Janice and Miller, John B}
}
@article {1360115,
	title = {Outcomes in resident-performed cataract surgeries with iris challenges: Results from the Perioperative Care for Intraocular Lens study},
	journal = {J Cataract Refract Surg},
	volume = {44},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {1469-1477},
	abstract = {PURPOSE: To assess the outcomes of resident-performed cataract surgeries with iris challenges and to compare these outcomes with similar surgeries performed by attending surgeons. SETTING: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. DESIGN: Retrospective chart review. METHODS: All cases of cataract extraction by phacoemulsification with intraocular lens implantation, performed by comprehensive ophthalmologists between January 1 and December 31, 2014, were reviewed. Cases with preoperative or intraoperative miosis, iris prolapse, and intraoperative floppy iris syndrome, were included for analysis. Visual outcomes and the rate of perioperative adverse events were compared between resident and attending surgeon cases. Factors predicting adverse events were also assessed. RESULTS: In total, 1931 eye cases of 1434 patients were reviewed, and 65 resident cases and 168 attending surgeon cases were included. The mean logarithm of the minimum angle of resolution corrected distance visual acuity was better in the resident group\&nbsp;1\&nbsp;month after surgery (0.051\&nbsp;{\textpm}\&nbsp;0.10 [SD] versus 0.132\&nbsp;{\textpm}\&nbsp;0.30, P\&nbsp;=\&nbsp;.03); however, the difference was eliminated when controlling for macular disease. The mean operative time was 43.8\&nbsp;{\textpm}\&nbsp;26.5\&nbsp;minutes and 30.9\&nbsp;{\textpm}\&nbsp;12.6\&nbsp;minutes for cases performed by resident surgeons and attending surgeons, respectively (P\&nbsp;\&nbsp;.0001). Residents utilized supplemental pharmacologic dilation or retraction more frequently than attending surgeons (98\% versus 87\% of cases, P\&nbsp;=\&nbsp;.008). The overall rate of adverse events was no different between residents and attending surgeons (P\&nbsp;=\&nbsp;0.16). Dense nuclear sclerosis predicted adverse events in cataract cases with iris challenges (adjusted odds ratio, 1.86; 95\% confidence interval, 1.17-2.94; P\&nbsp;=\&nbsp;.001). CONCLUSION: Although requiring longer operative times and more surgical manipulation, residents who performed cataract surgeries with iris challenges achieved outcomes comparable to those performed by attending surgeons, and residents should be given the opportunity to operate on these eyes.},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2018.08.019},
	author = {Moustafa, Giannis A and Borkar, Durga S and McKay, K Matthew and Eton, Emily A and Koulisis, Nicole and Lorch, Alice C and Kloek, Carolyn E and PCIOL Study Group}
}
@article {1586196,
	title = {Healthcare disparities contribute to missed follow-up visits after cataract surgery in the USA: results from the perioperative care for intraocular lens study},
	journal = {BMJ Open},
	volume = {11},
	number = {3},
	year = {2021},
	month = {2021 Mar 17},
	pages = {e038565},
	abstract = {OBJECTIVE: To identify factors that contribute to missed cataract surgery follow-up visits, with an emphasis on socioeconomic and demographic factors. METHODS: In this retrospective cohort study, patients who underwent cataract extraction by phacoemulsification at Massachusetts Eye and Ear between 1 January and 31 December 2014 were reviewed. Second eye cases, remote and international patients, patients with foreign insurance and combined cataract cases were excluded. RESULTS: A total of 1931 cases were reviewed and 1089 cases, corresponding to 3267 scheduled postoperative visits, were included. Of these visits, 157 (4.8\%) were missed. Three (0.3\%) postoperative day 1, 40 (3.7\%) postoperative week 1 and 114 (10.5\%) postoperative month 1 visits were missed. Age\&lt;30 years (adjusted OR (aOR)=8.2, 95\% CI 1.9 to 35.2) and >=90 years (aOR=5.7, 95\% CI 2.0 to 15.6) compared with patients aged 70-79 years, estimated travel time of \&gt;2 hours (aOR=3.2, 95\% CI 1.4 to 7.4), smokers (aOR=2.7, 95\% CI 1.6 to 4.8) and complications identified up to the postoperative visit (aOR=1.4, 95\% CI 1.0 to 2.1) predicted a higher rate of missed visits. Ocular comorbidities (aOR=0.7, 95\% CI 0.5 to 1.0) and previous visit best-corrected visual acuity (BCVA) of 20/50-20/80 (aOR=0.4, 95\% CI 0.3 to 0.7) and 20/90-20/200 (aOR=0.4, 95\% CI 0.2 to 0.9), compared with BCVA at the previous visit of 20/40 or better, predicted a lower rate of missed visits. Gender, race/ethnicity, language, education, income, insurance, alcohol use and season of the year were not associated with missed visits. CONCLUSIONS: Medical factors and demographic characteristics, including patient age and distance from the hospital, are associated with missed follow-up visits in cataract surgery. Additional studies are needed to identify disparities in cataract postoperative care that are population-specific. This information can contribute to the implementation of policies and interventions for addressing them.},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2020-038565},
	author = {Moustafa, Giannis A and Borkar, Durga S and Eton, Emily A and Koulisis, Nicole and Kloek, Carolyn E and PCIOL Study Group Members and PCIOL Study Group Members}
}
@article {1466903,
	title = {Optimization of cataract surgery follow-up: A standard set of questions can predict unexpected management changes at postoperative week one},
	journal = {PLoS One},
	volume = {14},
	number = {9},
	year = {2019},
	month = {2019},
	pages = {e0221243},
	abstract = {PURPOSE: There is limited evidence to inform the optimal follow-up schedule after cataract surgery. This study aims to determine whether a standardized question set can predict unexpected management changes (UMCs) at the postoperative week one (POW1) timepoint. SETTING: Massachusetts Eye and Ear, Harvard Medical School. DESIGN: Prospective cohort study. METHODS: Two-hundred-and-fifty-four consecutive phacoemulsification cases having attended an examination between postoperative days 5-14. A set of 7 {\textquoteright}Yes{\textquoteright} or {\textquoteright}No{\textquoteright} questions were administered to all participants by a technician at the POW1 visit. Patient answers along with perioperative patient information were recorded and analyzed. Outcomes were the incidence of UMCs at POW1. RESULTS: The incidence of UMCs was zero in uneventful cataract cases with unremarkable history and normal postoperative day one exam if no positive answers were given with the question set demonstrating 100\% sensitivity (p\&lt;0.0001). A test version with 5 questions was equally sensitive in detecting UMCs at POW1 after cataract surgery. CONCLUSION: In routine cataract cases with no positive answers to the current set of clinical questions, a POW1 visit is unlikely to result in a management change. This result offers the opportunity for eye care providers to risk-stratify patients who have had cataract surgery and individualize follow-up.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0221243},
	author = {Moustafa, Giannis A and Borkar, Durga S and Borboli-Gerogiannis, Sheila and Greenstein, Scott H and Lorch, Alice C and Vasan, Ryan A and Kloek, Carolyn E}
}
@article {1655713,
	title = {Primary Care Provider Familiarity and Compliance With Preferred Practice Patterns for Comprehensive Eye Examinations},
	journal = {Am J Ophthalmol},
	volume = {247},
	year = {2023},
	month = {2023 Mar},
	pages = {127-136},
	abstract = {PURPOSE: To assess primary care practitioners{\textquoteright} (PCPs) familiarity with American Academy of Ophthalmology Preferred Practice Pattern (PPP) guidelines on the frequency of comprehensive eye examinations (CEEs), and to explore their opinions and practices on counseling and referring patients for CEEs. DESIGN: Cross-sectional study. METHODS: Between February 1, 2019, and June 25, 2019, an anonymous survey was emailed to clinicians holding an MD, DO, PA, or NP degree, and residents at Brigham and Women{\textquoteright}s Hospital and the University of Oklahoma. Descriptive statistics of participants{\textquoteright} responses were reported. RESULTS: Regarding patient counseling on CEEs, 15.4\% of PCPs reported "always," 48.1\% "usually," and 36.5\% "seldom" or "never" doing so. Few PCPs (11.1\%) reported being able to describe the guidelines, and 63.9\% were unaware of their existence. A strong majority of PCPs (90.7\%) correctly referred a type 2 diabetic patient at their time of diagnosis, but a similar majority (77.8\%) prematurely referred a newly diagnosed type 1 diabetic patient. One in 7 PCPs (13.4\%) would refer a patient with family history of glaucoma only upon developing visual/ocular symptoms. Compared to other providers, PAs/NPs were more likely to recommend unnecessary CEEs for low-risk individuals (P\&nbsp;=\&nbsp;.009), whereas residents counseled patients less frequently (P\&nbsp;=\&nbsp;.003), were less likely to be familiar with PPP guidelines (P\&nbsp;=\&nbsp;.026), and were less likely to recommend appropriate follow-ups for patients with family history of glaucoma (P\&nbsp;=\&nbsp;.004). CONCLUSIONS: PCPs{\textquoteright} awareness of and familiarity with AAO CEE guidelines is variable and improves with provider age and experience. Efforts to improve PCP guideline awareness may be especially well suited to residents and mid-level practitioners.},
	keywords = {Cross-Sectional Studies, Female, Glaucoma, Humans, Practice Guidelines as Topic, Practice Patterns, Physicians{\textquoteright}, Primary Health Care, United States},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.10.003},
	author = {Moustafa, Giannis A and Liebman, Daniel L and Kabarriti, Gabriel and Lorch, Alice C and Vasan, Ryan A and Samal, Lipika and Nagykaldi, Zsolt J and Osman, Nora Y and Kloek, Carolyn E}
}
@article {1517215,
	title = {Paediatric ocular adnexal lymphoma: a population-based analysis},
	journal = {BMJ Open Ophthalmol},
	volume = {5},
	number = {1},
	year = {2020},
	month = {2020},
	pages = {e000483},
	abstract = {Objective: To investigate the incidence, clinicopathological characteristics and survival of ocular adnexal lymphoma (OAL) in the paediatric population. Methods and analysis: In this retrospective case series, the Surveillance, Epidemiology and End Results database was accessed to identify individuals with OAL <=18 years of age, diagnosed between 1973 and 2015. OAL located in the eyelid, conjunctiva, lacrimal apparatus and orbit were included. Main outcome measures were the age-adjusted incidence rates (IRs) per 1 000 000 population at risk (calculated for the period 2000-2015) and descriptive statistics of demographic and clinicopathological features. Results: The IR of paediatric OAL was 0.12 (95\% CI 0.08 to 0.16) per 1 000 000. Males (0.15; 95\% CI 0.10 to 0.22) and blacks (0.24; 95\% CI 0.13 to 0.42) had a higher tendency for OAL development. A total of 55 tumours in 54 children were identified. The majority were localised (78.4\%), conjunctival (49.1\%) lymphomas. Extranodal marginal zone lymphoma (EMZL, 45.5\%, n=25) was the most frequent subtype, followed by diffuse large B-cell lymphoma (DLBCL, 9.1\%, n=5), B lymphoblastic lymphoma (7.3\%, n=4), follicular lymphoma (5.5\%, n=3), Burkitt lymphoma (5.5\%, n=3), anaplastic large cell lymphoma (ALCL, 3.6\%, n=2), small lymphocytic lymphoma (1.8\%, n=1), diffuse large B-cell lymphoma, immunoblastic (1.8\%, n=1) and panniculitis-like T-cell lymphoma (1.8\%, n=1). Localised, low-grade, conjunctival lymphomas were frequently treated with complete excision with or without radiation, while high-grade and distant tumours usually received chemotherapy. Only 29.1\% of paediatric OAL cases were treated with radiation. Three out of five (60\%) patients with DLBCL died of lymphoma at a median follow-up of 21 (range 10-86) months, and 1 out of 2 (50\%) patients with ALCL died of lymphoma at 23 months from diagnosis. Conclusion: OAL in the paediatric population is rare. The majority of OAL are EMZL and are characterised by excellent prognosis. The histological subtype was found to be the main predictor of outcome with cancer-specific deaths observed in patients with DLBCL and ALCL.},
	issn = {2397-3269},
	doi = {10.1136/bmjophth-2020-000483},
	author = {Moustafa, Giannis A and Topham, Allan K and Aronow, Mary E and Vavvas, Demetrios G}
}
@article {280836,
	title = {Proton Radiation Therapy for the Treatment of Retinoblastoma.},
	journal = {Int J Radiat Oncol Biol Phys},
	volume = {90},
	number = {4},
	year = {2014},
	month = {2014 Nov 15},
	pages = {863-9},
	abstract = {PURPOSE: To investigate long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with proton radiation therapy (PRT). METHODS AND MATERIALS: This is a retrospective analysis of 49 retinoblastoma patients (60 eyes) treated with PRT between 1986 and\&nbsp;2012. RESULTS: The majority (84\%) of patients had bilateral disease, and nearly half (45\%) had received prior chemotherapy. At a median follow-up of 8\&nbsp;years (range, 1-24\&nbsp;years), no patients died of retinoblastoma or developed metastatic disease. The post-PRT enucleation rate was low (18\%), especially in patients with early-stage disease (11\% for patients with International Classification for Intraocular Retinoblastoma [ICIR] stage A-B disease vs 23\% for patients with ICIR stage C-D disease). Post-PRT ophthalmologic follow-up was available for 61\% of the preserved eyes (30 of 49): 14 of 30 eyes (47\%) had 20/40 visual acuity or better, 7 of 30 (23\%) had moderate visual acuity (20/40-20/600), and 9 of 30 (30\%) had little or no useful vision (worse than 20/600). Twelve of 60 treated eyes (20\%) experienced a post-PRT event requiring intervention, with cataracts the most common (4 eyes). No patients developed an in-field second malignancy. CONCLUSIONS: Long-term follow-up of retinoblastoma patients treated with PRT demonstrates that PRT can achieve high local control rates, even in advanced cases, and many patients retain useful vision in the treated eye. Treatment-related ocular side effects were uncommon, and no radiation-associated malignancies were observed.},
	issn = {1879-355X},
	doi = {10.1016/j.ijrobp.2014.07.031},
	author = {Mouw, Kent W and Sethi, Roshan V and Yeap, Beow Y and MacDonald, Shannon M and Chen, Yen-Lin E and Tarbell, Nancy J and Yock, Torunn I and Munzenrider, John E and Adams, Judith and Grabowski, Eric and Mukai, Shizuo and Shih, Helen A}
}
@article {1364519,
	title = {Mechanisms of inflammation in proliferative vitreoretinopathy: from bench to bedside},
	journal = {Mediators Inflamm},
	volume = {2012},
	year = {2012},
	month = {2012},
	pages = {815937},
	abstract = {Proliferative vitreoretinopathy (PVR) is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD). Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGRα), which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH), daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside.},
	keywords = {Animals, Clinical Trials as Topic, Daunorubicin, Fluorouracil, Heparin, Low-Molecular-Weight, Humans, Inflammation, Isotretinoin, Receptor, Platelet-Derived Growth Factor alpha, Vitreoretinopathy, Proliferative},
	issn = {1466-1861},
	doi = {10.1155/2012/815937},
	author = {Moysidis, Stavros N and Thanos, Aristomenis and Vavvas, Demetrios G}
}
@article {1586197,
	title = {Baltimore Reading and Eye Disease Study: vision outcomes of school-based eye care},
	journal = {Can J Ophthalmol},
	volume = {57},
	number = {1},
	year = {2022},
	month = {2022 Feb},
	pages = {36-40},
	abstract = {OBJECTIVE: There are unmet needs for refractive correction in the pediatric population, especially in high-poverty communities. We reported the impact of refractive correction on vision outcomes over a 2-year follow-up in the Baltimore Reading and Eye Disease Study. DESIGN: Prospective, school-based cohort study. PARTICIPANTS: Students of second and third grades who were prescribed glasses during baseline assessment. METHODS: We conducted baseline eye exams in 12 Baltimore public schools during the fall of school year 2014-15 with follow-up visits in the spring of school year 2014-15 (first follow-up) and school year 2015-16 (second follow-up). Visual acuity (VA) was measured at distance and near with correction. Refractive status was determined based on the eye with the larger refractive error and categorized as myopia, hyperopia, and astigmatism. MAIN OUTCOME MEASURES: VA in better-seeing and worse-seeing eye at first and second follow-up, and acuity improvement from baseline. RESULTS: In the 206 students (84\% African American) who completed the first follow-up, both distance (from 0.14 {\textpm} 0.20 to 0.05 {\textpm} 0.10 logMAR) and near presenting VA (from 0.08 {\textpm} 0.16 to 0.03 {\textpm} 0.06 logMAR) improved from the baseline assessment; children with more severe hyperopia showed improvement in near VA by 0.05 {\textpm} 0.16 logMAR. Children who were prescribed glasses through a school-based research study had improved vision, which was sustained into the following school year. CONCLUSIONS: Many second and third graders in Baltimore Schools needed refractive correction and benefited from provision of glasses with sustained vision improvement over the 2-year observation.},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2021.02.013},
	author = {Mudie, Lucy I and Guo, Xinxing and Slavin, Robert E and Madden, Nancy and Wolf, Rebecca and Owoeye, Josephine and Friedman, David S and Repka, Michael X and Collins, Megan E}
}
@article {1109861,
	title = {Morphometric Analysis of the Orbital Process of the Palatine Bone and its Relationship to Endoscopic Orbital Apex Surgery},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {3},
	year = {2018},
	month = {2018 May/Jun},
	pages = {254-257},
	abstract = {BACKGROUND: Endoscopic approaches to the orbit improve the ability to directly access apical lesions while minimizing manipulation of normal structures. Inferomedial orbital access is limited by the orbital process of the palatine bone (OPPB) which prevents dissection and retraction in the inferolateral vector.

OBJECTIVE: The objective of this study was to examine the morphometric characteristics of the OPPB and quantify the benefit of complete resection to surgical access.

METHODS: Morphometric osteologic measurements of the OPPB were performed in 59 human skulls. A radius subtended by the OPPB was calculated to generate a hemispheric dissection corridor achievable by complete resection of the OPPB. Cadaveric and live surgical dissections were then performed on 15 orbits to develop discreet endoscopic surgical landmarks which could be used to both identify the OPPB and verify complete resection.

RESULTS: The mean({\textpm} SD) radius of the OPPB was 0.47 {\textpm} 0.28 cm. Complete OPPB resection provided an additional 0.36 {\textpm} 0.42 cm of surgical exposure within the inferomedial apex. Relative to the Caucasian (n = 27) skulls, the radii in the Asian (n = 27) and African (n = 5) skulls were significantly smaller (p < 0.001 and p = 0.02, respectively).

CONCLUSION: The OPPB significantly limits surgical access to the inferomedial orbital apex during endoscopic approaches. Complete surgical resection of the OPPB improves surgical exposure facilitating retraction of the inferior rectus muscle and circumferential dissection of lesions within this space. Knowledge of the morphology and clinical relevance of this structure provides an opportunity to improve surgical exposure for relevant pathologic assessment and optimize endoscopic surgical outcomes.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000940},
	author = {Mueller, Sarina K and Freitag, Suzanne K and Bleier, Benjamin S}
}
@article {1304388,
	title = {Revision eDCR using a superior pedicled mucosal flap},
	journal = {Orbit},
	year = {2018},
	month = {2018 Mar 08},
	pages = {1-6},
	abstract = {BACKGROUND: Endoscopic dacryocystorhinostomies (eDCRs) show patency rates between 81\% and 94\%. However, dacryocystorhinostomy (DCR) failure and the need for revision remain a significant challenge. One of the principal challenges in revision eDCR is the need to surgically identify the correct osteotomy site and maintain long-term patency in the setting of previously instrumented and potentially scarred tissue. At the same time, the surgeon must assume that the blood supply to the commonly described anterior and posteriorly pedicled flaps has been compromised. OBJECTIVE: The objective of the study is to describe a novel flap technique for revision eDCR. METHODS: The superior based mucosal flap is a novel technique that provides a vascularized mucosa preserving technique in revision eDCR despite previous instrumentation of the lacrimal system. This technique provides wide exposure of the revision osteotomy site while simultaneously allowing a viable mucosal flap to be replaced at the conclusion of the procedure, thereby minimizing bone exposure and cicatricial restenosis. RESULTS: The authors have utilized this technique in 13 procedures with 100\% positive identification of the lacrimal sac, a 0\% complication rate, and a 100\% success rate after a mean follow-up of 26.93\&nbsp;{\textpm}\&nbsp;10.33\&nbsp;months (range 6-35\&nbsp;months). CONCLUSION: The eDCR using the superior pedicled mucosal flap provides excellent exposure of the maxillary bone and the lacrimal sac. This method preserves vascularity of the flap using a superiorly based pedicle which is typically inviolate during both open and endoscopic primary DCR. The mucosal flap can then be replaced, thereby minimizing bone exposure and optimizing patency.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2018.1444062},
	author = {Mueller, Sarina K and Freitag, Suzanne K and Lefebvre, Daniel R and Lee, Nahyoung G and Bleier, Benjamin S}
}
@article {1195241,
	title = {Long-term impact of endoscopic orbital decompression on sinonasal-specific quality of life},
	journal = {Laryngoscope},
	volume = {128},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {785-788},
	abstract = {OBJECTIVE: Endoscopic orbital decompression (EOD) is the workhorse surgical intervention for severe thyroid eye disease in Graves disease. Although EOD is a safe and effective procedure, the objective of this study is to determine the impact of orbital decompression on long-term sinonasal-pecific quality of life.

METHODS: Retrospective study of 27 patients who underwent EOD by a single surgeon. The primary endpoint was change in preoperative 22-item Sinonasal Outcomes Test (SNOT-22) score at a minimum of 1 year. The secondary endpoint was to determine whether the performance of septoplasty for surgical access in patients without nasal obstruction impacted domain 1 (i.e., rhinologic domain) and total SNOT-22 scores.

RESULTS: The mean follow-up was 25.7 {\textpm} 11.4 months. Domain 1 scores significantly increased at the first postoperative visit (P <= 0.01) and returned to baseline values between 1 and 3 months. At 1 year, significant improvements in both total score and domain 4 and 5 (psychological and sleep dysfunction, respectively) scores were seen (P < 0.01 for all scores). Septoplasty was not associated with a significant change in SNOT-22 score at 1 year (P = 0.48).

CONCLUSION: Endoscopic orbital decompression is associated at 1 year with a significant improvement in sinonasal-specific quality of life, which is driven by the psychological and sleep dysfunction domains. Adjunctive septoplasty has no significant impact on SNOT-22 scores.

LEVEL OF EVIDENCE: 4. Laryngoscope, 128:785-788, 2018.},
	issn = {1531-4995},
	doi = {10.1002/lary.26812},
	author = {Mueller, Sarina K and Miyake, Marcel M and Lefebvre, Daniel R and Freitag, Suzanne K and Bleier, Benjamin S}
}
@article {1137896,
	title = {Endoscopic DCR using bipedicled interlacing mucosal flaps},
	journal = {Laryngoscope},
	volume = {128},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {794-797},
	abstract = {OBJECTIVE: Obstruction of the nasolacrimal duct is a relatively common condition that affects patients of all ages, races, and sexes. The surgical gold standard for complete nasolacrimal duct obstruction and dacryocystitis is dacryocystorhinostomy (DCR). The purpose of this study was to describe a novel, bipedicled interlacing mucosal sparing flap technique for endoscopic DCR (eDCR).

METHODS: A posteriorly based mucosal flap over the fundus is combined with a novel, anteriorly based mucosal flap over the intraosseus portion of the nasolacrimal duct (NLD). This exposes a wide area of the maxillary bone, allowing for exposure and identification of the NLD/sac complex in a safer, more inferior position. The interlacing mucosal flaps may be replaced at the conclusion of the procedure, thereby minimizing bone exposure and maintaining excellent long-term patency.

RESULTS: The authors have utilized this technique in 55 procedures with 100\% positive identification of the NLD and lacrimal sac, 0\% complication rate, 100\% anatomical patency rate, and 96.4\% success rate after a minimal follow-up of 6 months.

DISCUSSION: The bipedicled interlacing flap technique for eDCR provides for safe and reproducible identification of the NLD and lacrimal sac while minimizing bone exposure and restenosis rate.

CONCLUSION: The bipedicled interlacing flap technique for eDCR provides for safe and reproducible identification of the NLD and lacrimal sac while minimizing bone exposure and restenosis rate.

LEVEL OF EVIDENCE: NA. Laryngoscope, 128:794-797, 2018.},
	issn = {1531-4995},
	doi = {10.1002/lary.26730},
	author = {Mueller, Sarina K and Freitag, Suzanne K and Lefebvre, Daniel R and Bleier, Benjamin S}
}
@article {1474193,
	title = {PD-1 melanocortin receptor dependent-Treg cells prevent autoimmune disease},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 Nov 15},
	pages = {16941},
	abstract = {Experimental autoimmune uveoretinitis (EAU) is a mouse model of human autoimmune uveitis marked by ocular autoantigen-specific regulatory immunity in the spleen. The melanocortin 5 receptor (MC5r) and adenosine 2 A receptor (A2Ar) are required for induction of post-EAU regulatory T cells (Tregs) which provide resistance to EAU. We show that blocking the PD-1/PD-L1 pathway prevented suppression of EAU by post-EAU Tregs. A2Ar induction of PD-1FoxP3 Tregs in uveitis patients was similar compared to healthy controls, but was significantly reduced with melanocortin stimulation. Further, lower body mass index correlated with responsiveness to stimulation of this pathway. These observations indicate an importance of the PD-1/PD-L1 pathway to provide resistance to relapsing uveitis and shows a reduced capacity of uveitis patients to induce Tregs when stimulated through melanocortin receptors, but that it is possible to bypass this part of the pathway through direct stimulation of A2Ar.},
	issn = {2045-2322},
	doi = {10.1038/s41598-019-53297-w},
	author = {Muhammad, Fauziyya and Wang, Dawei and Montieth, Alyssa and Lee, Stacey and Preble, Janine and Foster, C Stephen and Larson, Theresa A and Ding, Kai and Dvorak, Justin D and Lee, Darren J}
}
@article {1498244,
	title = {TIGIT A2Ar-Dependent anti-uveitic Treg cells are a novel subset of Tregs associated with resolution of autoimmune uveitis},
	journal = {J Autoimmun},
	volume = {111},
	year = {2020},
	month = {2020 Jul},
	pages = {102441},
	abstract = {Regulatory T cells (Tregs) are necessary to prevent autoimmune disease. As such, stable FoxP3 expression is required for the proper function of Tregs in the control of autoimmune disease. Different Treg subsets that utilize different mechanisms of suppression have been identified. The T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif (TIGIT) is a relatively new Treg cell marker that has a suppressive function. We have previously identified the adenosine 2A receptor (A2Ar) as a requirement for the emergence of Tregs following resolution of autoimmune disease. Using a FoxP3-GFP-Cre reporter mouse, we identify FoxP3 and {\textquoteright}exFoxP3{\textquoteright} cells, show FoxP3 and not exFoxP3 cells are suppressive. We further show FoxP3 cells express TIGIT, and are induced through A2Ar in healthy volunteers, but not patients with autoimmune disease. Furthermore, we show Tregs emerge in the target tissue at the onset of autoimmune disease in an A2Ar-dependent manner. In summary, we identify a novel subset of TIGIT Tregs that are induced through stimulation of the A2Ar.},
	issn = {1095-9157},
	doi = {10.1016/j.jaut.2020.102441},
	author = {Muhammad, Fauziyya and Wang, Dawei and McDonald, Trisha and Walsh, Marisa and Drenen, Kayla and Montieth, Alyssa and Foster, C Stephen and Lee, Darren J}
}
@article {1732546,
	title = {Non-Rigid Registration for High-Resolution Retinal Imaging},
	journal = {Diagnostics (Basel)},
	volume = {13},
	number = {13},
	year = {2023},
	month = {2023 Jul 06},
	abstract = {Adaptive optics provides improved resolution in ophthalmic imaging when retinal microstructures need to be identified, counted, and mapped. In general, multiple images are averaged to improve the signal-to-noise ratio or analyzed for temporal dynamics. Image registration by cross-correlation is straightforward for small patches; however, larger images require more sophisticated registration techniques. Strip-based registration has been used successfully for photoreceptor mosaic alignment in small patches; however, if the deformations along strips are not simple displacements, averaging can degrade the final image. We have applied a non-rigid registration technique that improves the quality of processed images for mapping cones over large image patches. In this approach, correction of local deformations compensates for local image stretching, compressing, bending, and twisting due to a number of causes. The main result of this procedure is improved definition of retinal microstructures that can be better identified and segmented. Derived metrics such as cone density, wall-to-lumen ratio, and quantification of structural modification of blood vessel walls have diagnostic value in many retinal diseases, including diabetic retinopathy and age-related macular degeneration, and their improved evaluations may facilitate early diagnostics of retinal diseases.},
	issn = {2075-4418},
	doi = {10.3390/diagnostics13132285},
	author = {Mujat, Mircea and Akula, James D and Fulton, Anne B and Ferguson, R Daniel and Iftimia, Nicusor}
}
@article {1798486,
	title = {Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology},
	journal = {Diagnostics (Basel)},
	volume = {14},
	number = {2},
	year = {2024},
	month = {2024 Jan 15},
	abstract = {The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.},
	issn = {2075-4418},
	doi = {10.3390/diagnostics14020184},
	author = {Mujat, Mircea and Sampani, Konstantina and Patel, Ankit H and Zambrano, Ronald and Sun, Jennifer K and Wollstein, Gadi and Ferguson, R Daniel and Schuman, Joel S and Iftimia, Nicusor}
}
@article {1782331,
	title = {Cellular-Level Analysis of Retinal Blood Vessel Walls Based on Phase Gradient Images},
	journal = {Diagnostics (Basel)},
	volume = {13},
	number = {22},
	year = {2023},
	month = {2023 Nov 08},
	abstract = {Diseases such as diabetes affect the retinal vasculature and the health of the neural retina, leading to vision problems. We describe here an imaging method and analysis procedure that enables characterization of the retinal vessel walls with cellular-level resolution, potentially providing markers for eye diseases. Adaptive optics scanning laser ophthalmoscopy is used with a modified detection scheme to include four simultaneous offset aperture channels. The magnitude of the phase gradient derived from these offset images is used to visualize the structural characteristics of the vessels. The average standard deviation image provides motion contrast and enables segmentation of the vessel lumen. Segmentation of blood vessel walls provides quantitative measures of geometrical characteristics of the vessel walls, including vessel and lumen diameters, wall thickness, and wall-to-lumen ratio. Retinal diseases may affect the structural integrity of the vessel walls, their elasticity, their permeability, and their geometrical characteristics. The ability to measure these changes is valuable for understanding the vascular effects of retinal diseases, monitoring disease progression, and drug testing. In addition, loss of structural integrity of the blood vessel wall may result in microaneurysms, a hallmark lesion of diabetic retinopathy, which may rupture or leak and further create vision impairment. Early identification of such structural abnormalities may open new treatment avenues for disease management and vision preservation. Functional testing of retinal circuitry through high-resolution measurement of vasodilation as a response to controlled light stimulation of the retina (neurovascular coupling) is another application of our method and can provide an unbiased evaluation of one{\textquoteright}s vision and enable early detection of retinal diseases and monitoring treatment results.},
	issn = {2075-4418},
	doi = {10.3390/diagnostics13223399},
	author = {Mujat, Mircea and Sampani, Konstantina and Patel, Ankit H and Sun, Jennifer K and Iftimia, Nicusor}
}
@article {1417569,
	title = {Mouse model of ocular hypertension with retinal ganglion cell degeneration},
	journal = {PLoS One},
	volume = {14},
	number = {1},
	year = {2019},
	month = {2019},
	pages = {e0208713},
	abstract = {OBJECTIVES: Ocular hypertension is a primary risk factor for glaucoma and results in retinal ganglion cell (RGC) degeneration. Current animal models of glaucoma lack severe RGC cell death as seen in glaucoma, making assessment of physiological mediators of cell death difficult. We developed a modified mouse model of ocular hypertension whereby long-lasting elevation of intraocular pressure (IOP) is achieved, resulting in significant reproducible damage to RGCs. RESULTS: In this model, microbeads are mixed with hyaluronic acid and injected into the anterior chamber of C57BL/6J mice. The hyaluronic acid allows for a gradual release of microbeads, resulting in sustained blockage of Schlemm{\textquoteright}s canal. IOP elevation was bimodal during the course of the model{\textquoteright}s progression. The first peak occurred 1 hours after beads injection, with an IOP value of 44.69 {\textpm} 6.00 mmHg, and the second peak occurred 6-12 days post-induction, with an IOP value of 34.91 {\textpm} 5.21 mmHg. RGC damage was most severe in the peripheral retina, with a loss of 64.1\% compared to that of untreated eyes, while the midperiphery exhibited a 32.4\% loss, 4 weeks following disease induction. CONCLUSIONS: These results suggest that sustained IOP elevation causes more RGC damage in the periphery than in the midperiphery of the retina. This model yields significant and reproducible RGC degeneration.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0208713},
	author = {Mukai, Ryo and Park, Dong Ho and Okunuki, Yoko and Hasegawa, Eiichi and Klokman, Garrett and Kim, Clifford B and Krishnan, Anitha and Gregory-Ksander, Meredith and Husain, Deeba and Miller, Joan W and Connor, Kip M}
}
@article {1593840,
	title = {Neuro-ophthalmic Complications of Immune-Checkpoint Inhibitors},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {241-249},
	abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized the field of oncology by modulating the immune cell-cancer cell interaction and thereby promoting immune system disinhibition in order to target several types of malignancies. There are three classes of immune checkpoint inhibitors (ICIs): anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1), and anti-programmed cell death ligand-1 (PD-L1).It is not uncommon for physicians across all specialties to encounter a patient with a history of malignancy and ICI exposure, necessitating familiarity with their potential complications. In this review article, we discuss the most common immune-related adverse events (irAEs) pertaining to the central and peripheral nervous systems and their potential afferent and efferent neuro-ophthalmic manifestations. Early recognition and treatment of these irAEs, and discontinuation of the offending ICI are all critical steps to prevent morbidity and mortality.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1890796},
	author = {Mukharesh, Loulwah and Chwalisz, Bart K}
}
@article {1638574,
	title = {Pseudotumor Cerebri Syndrome With COVID-19: A Case Series},
	journal = {J Neuroophthalmol},
	volume = {42},
	number = {3},
	year = {2022},
	month = {2022 Sep 01},
	pages = {e545-e547},
	keywords = {COVID-19, Humans, Papilledema, Pseudotumor Cerebri},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001467},
	author = {Mukharesh, Loulwah and Bouffard, Marc A and Fortin, Elizabeth and Brann, David H and Datta, Sandeep Robert and Prasad, Sashank and Chwalisz, Bart K}
}
@article {1661589,
	title = {Infliximab-Induced Optic Perineuritis and Facial Myositis},
	journal = {J Neuroophthalmol},
	volume = {42},
	number = {4},
	year = {2022},
	month = {2022 Dec 01},
	pages = {e583-e585},
	keywords = {Humans, Infliximab, Myositis, Optic Neuritis, Vision Disorders},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001349},
	author = {Mukharesh, Loulwah and Tinsley, Amanda}
}
@article {1615223,
	title = {Chronic Relapsing Inflammatory Optic Neuropathy (CRION)},
	journal = {Curr Opin Ophthalmol},
	volume = {32},
	number = {6},
	year = {2021},
	month = {2021 11 01},
	pages = {521-526},
	keywords = {Humans, Optic Nerve, Optic Nerve Diseases, Optic Neuritis, Recurrence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000804},
	author = {Mukharesh, Loulwah and Douglas, Vivian Paraskevi and Chwalisz, Bart K}
}
@article {1586186,
	title = {Perimetry Pitfalls in the Era of COVID-19},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {3},
	year = {2021},
	month = {2021 09 01},
	pages = {e283-e285},
	keywords = {Adult, COVID-19, Female, Humans, Magnetic Resonance Imaging, SARS-CoV-2, Scotoma, Visual Field Tests, Visual Fields},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001231},
	author = {Mukharesh, Loulwah and Torun, Nurhan and Bouffard, Marc A}
}
@article {369076,
	title = {Ultrastructure of adenovirus keratitis.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {1},
	year = {2015},
	month = {2015 Jan},
	pages = {472-7},
	abstract = {PURPOSE: We determined the ultrastructure of mouse adenovirus keratitis, a model for human adenovirus keratitis. METHODS: Adenovirus keratitis was induced in C57Bl/6j mice by intrastromal injection of human adenovirus species D type 37 (HAdV-D37) with a heat-pulled, glass, micropipette needle under compressed air. At select time points after infection, mice were euthanized and their corneas removed, fixed, and sectioned at 70-nm thickness for electron microscopy. RESULTS: Injection of HAdV-D37 into the mouse corneal stroma placed virus predominantly in the pericellular corneal stromal matrix. Virus was seen bound to and entering stromal cells at 1 and 2 hours after infection, respectively. Cell membrane transit by virus was seen to involve two distinct structures resembling caveolae and macropinosomes. However, later during infection intracellular virus was not seen within membrane-bound organelles. By 8 hours after infection, intracellular virus had accumulated into densely packed, perinuclear arrays. Virus disassembly was not obvious at any time point after infection. Infiltrating neutrophils seen by one day after infection had engulfed degraded stromal cells by 4 days after infection. CONCLUSIONS: By transmission electron microscopy, injected HAdV-D37 readily enters stromal cells in the C57Bl/6j mouse cornea and induces stromal inflammation, as was shown previously by light microscopy. However, electron microscopy also revealed dense, static arrays of intracytoplasmic virus, suggesting a block in viral capsid disassembly and viral DNA nuclear entry. These findings may explain why human adenoviruses do not replicate in the mouse corneal stroma.},
	keywords = {Adenoviridae, Adenovirus Infections, Human, Animals, Corneal Stroma, Disease Models, Animal, Eye Infections, Viral, Female, Keratitis, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15635},
	author = {Mukherjee, Santanu and Zhou, Xiaohong and Rajaiya, Jaya and Chodosh, James}
}
@article {503941,
	title = {In Vivo Confocal Microscopy Demonstrates Bilateral Loss of Endothelial Cells in Unilateral Herpes Simplex Keratitis.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {8},
	year = {2015},
	month = {2015 Jul 1},
	pages = {4899-906},
	abstract = {PURPOSE: To report bilateral corneal endothelial cell density (ECD), as well as its correlation with subbasal nerve changes, in patients with unilateral herpes simplex keratitis (HSK). METHODS: Thirty-six eyes of 36 patients with corneal scarring caused by HSK, as well as their respective contralateral clinically unaffected eyes, were prospectively studied and compared with 26 eyes of 26 healthy volunteers. In vivo confocal microscopy and corneal sensation of the central cornea were performed bilaterally in all patients and in one random eye of controls. The ECD and subbasal corneal nerve density, including the lengths of total nerves, main trunks, and branches were evaluated and correlated to central corneal sensation. RESULTS: The ECD was significantly lower in eyes affected with HSK than in controls (2304 {\textpm} 578 vs. 2940 {\textpm} 370 cells/mm2, P \&lt; 0.0001). Surprisingly, lower ECD was also detected in contralateral clinically unaffected eyes (2548 {\textpm} 423), compared to controls (P = 0.02). Both affected and contralateral eyes showed decrease in total nerve length, compared to controls (10.0 {\textpm} 6.3 vs. 17.6 {\textpm} 6.3 vs. 21.9 {\textpm} 4.3 mm/mm2, respectively; P \&lt; 0.05 for all). The ECD correlated positively with total nerve length (r = 0.39, P = 0.0009) and with corneal sensation (r = 0.31, P = 0.009). CONCLUSIONS: In vivo confocal microscopy findings demonstrated alterations in corneal ECD in both affected and clinically unaffected contralateral eyes of patients with unilateral HSK. Moreover, the positive significant correlation between the ECD and the subbasal nerve density may suggest a potential link between corneal innervation and corneal endothelial cell homeostasis.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-16527},
	author = {M{\"u}ller, Rodrigo T and Pourmirzaie, Roxanna and Pavan-Langston, Deborah and Cavalcanti, Bernardo M and Aggarwal, Shruti and Col{\'o}n, Clara and Jamali, Arsia and Cruzat, Andrea and Hamrah, Pedram}
}
@article {509146,
	title = {Degeneration and Regeneration of Subbasal Corneal Nerves after Infectious Keratitis: A Longitudinal InVivo Confocal Microscopy Study.},
	journal = {Ophthalmology},
	volume = {122},
	number = {11},
	year = {2015},
	month = {2015 Nov},
	pages = {2200-9},
	abstract = {PURPOSE: To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during the acute phase, cessation of treatment, and the recovery phase by in\&nbsp;vivo confocal microscopy (IVCM). DESIGN: Prospective, longitudinal, case-control, single-center study. PARTICIPANTS: Fifty-six eyes of 56 patients with the diagnosis of bacterial (n\&nbsp;= 28), fungal (n\&nbsp;= 15), or Acanthamoeba (n\&nbsp;= 13) keratitis were included in the study. Thirty eyes of 30 normal volunteers constituted the control group. METHODS: Corneal sensation and serial IVCM of the central cornea were performed prospectively using the Heidelberg Retina Tomograph 3/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany). The IVCM images were assessed at 3 time points: at the acute phase (first visit to the cornea service), at cessation of antimicrobial treatment, and up to 6 months after the resolution of infection. MAIN OUTCOME MEASURES: Total nerve number and length, main nerve trunks, branching, and corneal sensation were assessed during the follow-up period. RESULTS: Corneal nerves were reduced significantly during the acute phase in eyes with IK compared with controls across all subgroups, with total nerve length of 5.47{\textpm}0.69 mm/mm(2) versus 20.59{\textpm}1.06 mm/mm(2) (P \&lt;0.0001). At the cessation of treatment, corneal nerves in patients with IK had regenerated, including total nerve length (8.49{\textpm}0.94 mm/mm(2); P\&nbsp;= 0.02) and nerve branch length (4.80{\textpm}0.37 mm/mm(2); P\&nbsp;= 0.005). During the recovery phase, after resolution of infection, corneal nerves regenerated further, including total nerve length (12.13{\textpm}1.97 mm/mm(2); P\&nbsp;= 0.005), main nerve trunk length (5.80{\textpm}1.00 mm/mm(2); P\&nbsp;= 0.01), and nerve branch length (6.33{\textpm}0.76 mm/mm(2); P\&nbsp;= 0.003) as compared with the acute phase, but were still significantly lower when compared with controls (P \&lt; 0.05 for all parameters). Corneal degeneration and regeneration correlated with corneal sensation (r\&nbsp;= 0.47; P\&nbsp;= 0.0009). CONCLUSIONS: Patients with IK who sustain profound loss of corneal nerves during the acute phase of infection demonstrate increased corneal nerve density during the first 6 months after the resolution of infection. However, despite significant nerve regeneration, corneal nerve density does not recover fully and remains low compared to controls. By providing an objective methodology to monitor corneal re-innervation, IVCM adds potentially important findings that may have implications for clinical management and surgical planning.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.06.047},
	author = {M{\"u}ller, Rodrigo T and Abedi, Farshad and Cruzat, Andrea and Witkin, Deborah and Baniasadi, Neda and Cavalcanti, Bernardo M and Jamali, Arsia and Chodosh, James and Dana, Reza and Pavan-Langston, Deborah and Hamrah, Pedram}
}
@article {1761931,
	title = {Intravitreal Therapy for Uveitic Macular Edema-Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results},
	journal = {Ophthalmology},
	volume = {130},
	number = {9},
	year = {2023},
	month = {2023 Sep},
	pages = {914-923},
	abstract = {PURPOSE: To evaluate the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab. DESIGN: Single-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes. METHODS: Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME received the same treatment in both eyes. MAIN OUTCOME MEASURES: The primary outcome, measured at 12 weeks, was reduction in central subfield thickness (CST) expressed as a proportion of baseline (CST per CST at baseline) assessed with spectral-domain OCT by readers masked to treatment assignment. Secondary outcomes included improvement and resolution of ME, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP). RESULTS: One hundred ninety-four participants (225 eligible eyes) were randomized to dexamethasone (n\&nbsp;= 65 participants and 77 eyes), methotrexate (n\&nbsp;= 65 participants and 79 eyes), or ranibizumab (n\&nbsp;= 64 participants and 69 eyes). All received at least 1 injection of the assigned treatment. At the 12-week primary outcome point, each group showed significant reductions in CST relative to baseline: 35\%, 11\%, and 22\% for dexamethasone, methotrexate, and ranibizumab, respectively. Reduction of ME was significantly greater in the dexamethasone group than for either methotrexate (P \&lt; 0.01) or ranibizumab (P\&nbsp;= 0.018). Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P \&lt; 0.001). Elevations of IOP by 10 mmHg, to 24 mmHg or more, or both were more common in the dexamethasone group; IOP spikes to 30 mmHg or more were uncommon overall and were not significantly different among groups. Reductions in BCVA of 15 letters or more were more common in the methotrexate group and typically were attributable to persistent ME. CONCLUSIONS: At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent ME than methotrexate or ranibizumab. Risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or more were infrequent. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Angiogenesis Inhibitors, Dexamethasone, Glucocorticoids, Humans, Intravitreal Injections, Macula Lutea, Macular Edema, Methotrexate, Ranibizumab, Treatment Outcome, Uveitis},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.04.011},
	author = {Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group, Writing Committee: and Acharya, Nisha R and Vitale, Albert T and Sugar, Elizabeth A and Holbrook, Janet T and Burke, Alyce E and Thorne, Jennifer E and Altaweel, Michael M and Kempen, John H and Jabs, Douglas A}
}
@article {382611,
	title = {Vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms.},
	journal = {J Comp Neurol},
	volume = {523},
	number = {11},
	year = {2015},
	month = {2015 Aug 1},
	pages = {1639-63},
	abstract = {Current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. We developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. By engineering the vesicular stomatitis virus (VSV) to encode a fluorophore and either the rabies virus glycoprotein (RABV-G) or its own glycoprotein (VSV-G), we created viruses that can transsynaptically label neuronal circuits in either the retrograde or anterograde direction, respectively. The vectors were investigated for their utility as polysynaptic tracers of chicken and zebrafish visual pathways. They showed patterns of connectivity consistent with previously characterized visual system connections, and revealed several potentially novel connections. Further, these vectors were shown to infect neurons in several other vertebrates, including Old and New World monkeys, seahorses, axolotls, and Xenopus. They were also shown to infect two invertebrates, Drosophila melanogaster, and the box jellyfish, Tripedalia cystophora, a species previously intractable for gene transfer, although no clear evidence of transsynaptic spread was observed in these species. These vectors provide a starting point for transsynaptic tracing in most vertebrates, and are also excellent candidates for gene transfer in organisms that have been refractory to other methods.},
	issn = {1096-9861},
	doi = {10.1002/cne.23761},
	author = {Mundell, Nathan A and Beier, Kevin T and Pan, Y Albert and Lapan, Sylvain W and G{\"o}z Ayt{\"u}rk, Didem and Berezovskii, Vladimir K and Wark, Abigail R and Drokhlyansky, Eugene and Bielecki, Jan and Born, Richard T and Schier, Alexander F and Cepko, Constance L}
}
@article {439626,
	title = {Eye growth in term- and preterm-born eyes modeled from magnetic resonance images.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {5},
	year = {2015},
	month = {2015 May 1},
	pages = {3121-31},
	abstract = {PURPOSE: We generated a model of eye growth and tested it against an eye known to develop abnormally, one with a history of retinopathy of prematurity (ROP). METHODS: We reviewed extant magnetic resonance images (MRIs) from term and preterm-born patients for suitable images (n = 129). We binned subjects for analysis based upon postmenstrual age at birth (in weeks) and ROP history ("Term" >= 37, "Premature" <= 32 with no ROP, "ROP" <= 32 with ROP). We measured the axial positions and curvatures of the cornea, anterior and posterior lens, and inner retinal surface. We fit anterior chamber depth (ACD), posterior segment depth (PSD), axial length (AL), and corneal and lenticular curvatures with logistic growth curves that we then evaluated for significant differences. We also measured the length of rays from the centroid to the surface of the eye at 5{\textdegree} intervals, and described the length versus age relationship of each ray, Lray(x), using the same logistic growth curve. We determined the rate of ray elongation, Eray(x), from Lraydy/dx. Then, we estimated the scleral growth that accounted for Eray(x), G(x), at every age and position. RESULTS: Relative to Term, development of ACD, PSD, AL, and corneal and lenticular curvatures was delayed in ROP eyes, but not Premature eyes. In Term infants, G(x) was fast and predominantly equatorial; in age-matched ROP eyes, maximal G(x) was offset by approximately 90{\textdegree}. CONCLUSIONS: We produced a model of normal eye growth in term-born subjects. Relative to normal, the ROP eye is characterized by delayed, abnormal growth.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15980},
	author = {Munro, Robert J and Fulton, Anne B and Chui, Toco Y P and Moskowitz, Anne and Ramamirtham, Ramkumar and Hansen, Ronald M and Prabhu, Sanjay P and Akula, James D}
}
@article {1664975,
	title = {A normative database of wide-field swept-source optical coherence tomography angiography quantitative metrics in a large cohort of healthy adults},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	year = {2023},
	month = {2023 Jan 21},
	abstract = {PURPOSE: Data from healthy eyes is needed to interpret optical coherence tomography angiography (OCTA) findings. However, very little normative data is available for wide-field swept-source OCTA (WF SS-OCTA), particularly 12 {\texttimes} 12-mm and disc-centered angiograms. Therefore, we aim to report quantitative metrics in a large sample of control eyes. METHODS: In this cross-sectional observational study, 482 eyes of 375 healthy adults were imaged on the 100\&nbsp;kHz Zeiss PLEX{\textregistered} Elite 9000 using protocols centered on the fovea (3 {\texttimes} 3, 6 {\texttimes} 6, and 12 {\texttimes} 12-mm) and optic disc (6 {\texttimes} 6 and 12 {\texttimes} 12-mm) between December 2018 and January 2022. The ARI Network (Zeiss Portal v5.4) was used to calculate vessel density (VD) and vessel skeletonized density (VSD) in the superficial capillary plexus, deep capillary plexus, and whole retina, as well as foveal avascular zone (FAZ) parameters. Mixed-effect multiple linear regression models were used for statistical analysis. RESULTS: The subjects{\textquoteright} median age was 55 (38-63) years, and 201 (53.6\%) were female. Greater age and worse best-corrected visual acuity (BCVA) were associated with significantly lower VD and VSD (p \&lt; 0.05). VD and VSD differed based on race and cataract status, but not sex, on some scan protocols (p \&lt; 0.05). FAZ circularity decreased with age, and FAZ dimensions differed based on race and ethnicity in certain scan protocols. CONCLUSIONS: We report a large database of parafoveal and peripapillary vascular metrics in several angiogram sizes. In referencing these values, researchers must consider characteristics such as age, race, and BCVA, but will have a valuable point of comparison for OCTA measurements in pathologic settings.},
	issn = {1435-702X},
	doi = {10.1007/s00417-022-05963-5},
	author = {Munsell, Mary K and Garg, Itika and Duich, Margaret and Zeng, Rebecca and Baldwin, Grace and Wescott, Hannah E and Koch, Thomas and Wang, Kira L and Patel, Nimesh A and Miller, John B}
}
@article {1474185,
	title = {Trends in Diabetic Retinopathy, Visual Acuity, and Treatment Outcomes for Patients Living With Diabetes in a Fundus Photograph-Based Diabetic Retinopathy Screening Program in Bangladesh},
	journal = {JAMA Netw Open},
	volume = {2},
	number = {11},
	year = {2019},
	month = {2019 Nov 01},
	pages = {e1916285},
	abstract = {Importance: Diabetic retinopathy (DR) is the leading cause of low vision among working-age adults. An estimated 6.9 million people in Bangladesh were living with diabetes in 2017, which is projected to increase to more than 10 million people in 2025. Currently, no standardized and/or large-scale DR screening program exists in Bangladesh. Objective: To develop a novel fundus photograph-based eye screening model for early detection of DR to prevent vision loss in Bangladeshi individuals with diabetes. Design, Setting, and Participants: In this cross-sectional study, 49 264 patients with diabetes underwent opportunistic eye screening at 2 eye hospitals and 1 diabetic hospital in Bangladesh between June 1, 2010, and September 30, 2017. The data set was analyzed from April 8 to December 30, 2018. Technicians were trained to obtain 2-field digital fundus photographs and to grade each according to a standardized DR severity scale. Each patient was counseled and triaged for treatment using defined DR referral criteria. Main Outcomes and Measures: Primary DR grading outcomes, visual acuity, and treatment outcomes. Results: A total of 49 264 patients (54.3\% male; mean [SD] age, 50.8 [12.3] years) underwent DR screening during a 7-year period. The DR prevalence rate across all 3 sites was 33\% (95\% CI, 33\%-33\%). Prevalence rates varied by center (Chittagong, 64.6\% [95\% CI, 64.0\%-65.0\%]; Dhaka, 39.8\% [95\% CI, 39.0\%-41.0\%]; and Feni, 13.0\% [95\% CI, 13.0\%-14.0\%]). Across all age groups, male patients were at higher risk of prevalent DR than female patients (odds ratio, 1.99; 95\% CI, 1.90-2.07). The prevalence was 3.9\% for preproliferative DR, 7.8\% for proliferative DR, and 19.2\% for maculopathy. Individuals with DR had significantly worse visual acuity than those with no DR (best-corrected visual acuity, 0.35 vs 0.21 logMAR; P \&lt; .001). The rate of moderate visual impairment was 12.2\%, and the rate of blindness was 2.5\%. Primary treatments included laser photocoagulation (n = 1637), intravitreal injection (n = 1440), and vitrectomy (n = 309). Conclusions and Relevance: Screening Bangladeshi individuals known to have diabetes using fundus photography identified large numbers of patients with sight-threatening proliferative DR, maculopathy, and visual impairment or blindness. Expansion of eye screening services in Bangladesh is warranted as part of a national government eye care and diabetes health policy.},
	issn = {2574-3805},
	doi = {10.1001/jamanetworkopen.2019.16285},
	author = {Muqit, Mahiul M K and Kourgialis, Nick and Jackson-deGraffenried, Meredith and Talukder, Zaman and Khetran, Erica R and Rahman, Arifur and Chan, Weng Onn and Chowdury, Fakrhul A and Nag, Dipak and Ahmad, Jasmin and Friedman, David S}
}
@article {1364520,
	title = {Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration},
	journal = {Proc Natl Acad Sci U S A},
	volume = {109},
	number = {36},
	year = {2012},
	month = {2012 Sep 04},
	pages = {14598-603},
	abstract = {Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death in rd10 mice, a mouse model of retinitis pigmentosa caused by a mutation in a rod-specific gene. The expression of RIP3, a key regulator of programmed necrosis, was elevated in rd10 mouse retinas in the phase of cone but not rod degeneration. Although rd10 mice lacking Rip3 developed comparable rod degeneration to control rd10 mice, they displayed a significant preservation of cone cells. Ultrastructural analysis of rd10 mouse retinas revealed that a substantial fraction of dying cones exhibited necrotic morphology, which was rescued by Rip3 deficiency. Additionally, pharmacologic treatment with a RIP kinase inhibitor attenuated histological and functional deficits of cones in rd10 mice. Thus, necrotic mechanisms involving RIP kinase are crucial in cone cell death in inherited retinal degeneration, suggesting the RIP kinase pathway as a potential target to protect cone-mediated central and peripheral vision loss in patients with retinitis pigementosa.},
	keywords = {Analysis of Variance, Animals, Blotting, Western, Cyclic Nucleotide Phosphodiesterases, Type 6, DNA Primers, Electroretinography, Enzyme-Linked Immunosorbent Assay, In Situ Nick-End Labeling, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Microscopy, Electron, Transmission, Necrosis, Real-Time Polymerase Chain Reaction, Receptor-Interacting Protein Serine-Threonine Kinases, Retina, Retinal Cone Photoreceptor Cells, Retinitis Pigmentosa, Reverse Transcriptase Polymerase Chain Reaction, Statistics, Nonparametric},
	issn = {1091-6490},
	doi = {10.1073/pnas.1206937109},
	author = {Murakami, Yusuke and Matsumoto, Hidetaka and Roh, Miin and Suzuki, Jun and Hisatomi, Toshio and Ikeda, Yasuhiro and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1351172,
	title = {Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration},
	journal = {Cell Death Differ},
	volume = {21},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {270-7},
	abstract = {There is no known treatment for the dry form of an age-related macular degeneration (AMD). Cell death and inflammation are important biological processes thought to have central role in AMD. Here we show that receptor-interacting protein (RIP) kinase mediates necrosis and enhances inflammation in a mouse model of retinal degeneration induced by dsRNA, a component of drusen in AMD. In contrast to photoreceptor-induced apoptosis, subretinal injection of the dsRNA analog poly(I : C) caused necrosis of the retinal pigment epithelium (RPE), as well as macrophage infiltration into the outer retinas. In Rip3(-/-) mice, both necrosis and inflammation were prevented, providing substantial protection against poly(I : C)-induced retinal degeneration. Moreover, after poly(I : C) injection, Rip3(-/-) mice displayed decreased levels of pro-inflammatory cytokines (such as TNF-α and IL-6) in the retina, and attenuated intravitreal release of high-mobility group box-1 (HMGB1), a major damage-associated molecular pattern (DAMP). In vitro, poly(I : C)-induced necrosis were inhibited in Rip3-deficient RPE cells, which in turn suppressed HMGB1 release and dampened TNF-α and IL-6 induction evoked by necrotic supernatants. On the other hand, Rip3 deficiency did not modulate directly TNF-α and IL-6 production after poly(I : C) stimulation in RPE cells or macrophages. Therefore, programmed necrosis is crucial in dsRNA-induced retinal degeneration and may promote inflammation by regulating the release of intracellular DAMPs, suggesting novel therapeutic targets for diseases such as AMD. },
	keywords = {Animals, Apoptosis, Cell Death, Cell Survival, Cells, Cultured, Inflammation, Mice, Mice, Inbred C57BL, Mice, Knockout, Necrosis, Poly I-C, Receptor-Interacting Protein Serine-Threonine Kinases, Receptors, Pattern Recognition, Retinal Pigment Epithelium, RNA, Double-Stranded},
	issn = {1476-5403},
	doi = {10.1038/cdd.2013.109},
	author = {Murakami, Y and Matsumoto, H and Roh, M and Giani, A and Kataoka, K and Morizane, Y and Kayama, M and Thanos, A and Nakatake, S and Notomi, S and Hisatomi, T and Ikeda, Y and Ishibashi, T and Connor, K M and Miller, J W and Vavvas, D G}
}
@article {1363163,
	title = {Photoreceptor cell death and rescue in retinal detachment and degenerations},
	journal = {Prog Retin Eye Res},
	volume = {37},
	year = {2013},
	month = {2013 Nov},
	pages = {114-40},
	abstract = {Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss.},
	keywords = {Animals, Apoptosis, Autophagy, Caspases, Cell Death, GTPase-Activating Proteins, Humans, Photoreceptor Cells, Vertebrate, Retinal Degeneration, Retinal Detachment, Signal Transduction},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2013.08.001},
	author = {Murakami, Yusuke and Notomi, Shoji and Hisatomi, Toshio and Nakazawa, Toru and Ishibashi, Tatsuro and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1615201,
	title = {Eye-tunes: role of music in ophthalmology and vision sciences},
	journal = {Ther Adv Ophthalmol},
	volume = {13},
	year = {2021},
	month = {2021 Jan-Dec},
	pages = {25158414211040890},
	abstract = {Although the healing effect of music has been recognized since time immemorial, there has been a renewed interest in its use in modern medicine. This can be attributed to the increasing focus on holistic healing and on the subjective and objective aspects of well-being. In ophthalmology, this has ranged from using music for patients undergoing diagnostic procedures and surgery, as well as for doctors and the operation theatre staff during surgical procedures. Music has proven to be a potent nonpharmacological sedative and anxiolytic, allaying both the pain and stress of surgery. This review aims to explore the available evidence about the role of music as an adjunct for diagnostic and surgical procedures in current ophthalmic practices.},
	issn = {2515-8414},
	doi = {10.1177/25158414211040890},
	author = {Muralidharan, Shruti and Ichhpujani, Parul and Bhartiya, Shibal and Singh, Rohan Bir}
}
@article {416831,
	title = {Drug-induced Bilateral Secondary Angle-Closure Glaucoma: A Literature Synthesis.},
	journal = {J Glaucoma},
	volume = {25},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {e99-e105},
	abstract = {PURPOSE: We performed a literature synthesis to identify the full spectrum of compounds implicated in drug-induced, bilateral secondary angle-closure glaucoma (2{\textdegree} ACG). METHODS: Systematic PubMed literature review identified relevant bilateral 2{\textdegree} ACG case reports. We evaluated these reports with both the Naranjo adverse drug reaction probability scale to assess the causality of reported drug reactions and a 2{\textdegree} ACG scale scoring system we developed to determine the likelihood that the event represented bilateral 2{\textdegree} ACG. Two independent graders performed these analyses and their scores were averaged for interpretation. The Naranjo scale ranges from -4 to +13 and the drug reaction was considered definite if the score was >=9, probable if 5 to 8, possible if 1 to 4, and doubtful if <=0. The 2{\textdegree} ACG score ranges from 0 to 7. We considered a 2{\textdegree} ACG score of >=4 as evidence of significant likelihood that the drug reaction represented bilateral 2{\textdegree} ACG. RESULTS: No drug had a definite Naranjo score, but the following drug entities had probable Naranjo scores and 2{\textdegree} ACG scores >=4: acetazolamide, "anorexiant mix," bupropion, cabergoline, "ecstasy," escitalopram, flavoxate, flucloxacillin, hydrochlorothiazide, hydrochlorothiazide/triamterene, mefenamic acid, methazolamide, oseltamivir, topiramate, topiramate/bactrim, and venlafaxine. Root chemical analysis revealed that sulfur-containing and non-sulfur-containing compounds contributed to bilateral 2{\textdegree} ACG. CONCLUSIONS: Several compound preparations were implicated in drug-induced bilateral 2{\textdegree} ACG. Treating physicians should be aware that some forms of recreational drug use, which the patient may not admit to, could contribute to this vision-threatening side effect.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000270},
	author = {Murphy, Rory M and Bakir, Belal and O{\textquoteright}Brien, Colm and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1615206,
	title = {Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina},
	journal = {Cells},
	volume = {10},
	number = {9},
	year = {2021},
	month = {2021 Sep 16},
	abstract = {Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in the ganglion cell layer (GCL) of the retina and axons in the optic nerve. Retinal arteriole responses were measured in isolated retinas by video microscopy. The levels of reactive oxygen species (ROS) were assessed in retinal cryosections and redox gene expression was determined in isolated retinas by quantitative PCR. I/R markedly reduced cell number in the GCL and axon number in the optic nerve of the vehicle-treated mice. In contrast, only a negligible reduction in cell and axon number was observed following I/R in the betulinic acid-treated mice. Endothelial function was markedly reduced and ROS levels were increased in retinal arterioles of vehicle-exposed eyes following I/R, whereas betulinic acid partially prevented vascular endothelial dysfunction and ROS formation. Moreover, betulinic acid boosted mRNA expression for the antioxidant enzymes SOD3 and HO-1 following I/R. Our data provide evidence that betulinic acid protects from I/R injury in the mouse retina. Improvement of vascular endothelial function and the reduction in ROS levels appear to contribute to the neuroprotective effect.},
	issn = {2073-4409},
	doi = {10.3390/cells10092440},
	author = {Musayeva, Aytan and Unkrig, Johanna C and Zhutdieva, Mayagozel B and Manicam, Caroline and Ruan, Yue and Laspas, Panagiotis and Chronopoulos, Panagiotis and G{\"o}bel, Marie L and Pfeiffer, Norbert and Brochhausen, Christoph and Daiber, Andreas and Oelze, Matthias and Li, Huige and Xia, Ning and Gericke, Adrian}
}
@article {1586137,
	title = {Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics},
	journal = {Nat Med},
	volume = {27},
	number = {3},
	year = {2021},
	month = {2021 03},
	pages = {546-559},
	abstract = {Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2TMPRSS2 cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.},
	keywords = {Adult, Aged, Aged, 80 and over, Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, Cathepsin L, COVID-19, Datasets as Topic, Demography, Female, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Lung, Male, Middle Aged, Organ Specificity, Respiratory System, SARS-CoV-2, Sequence Analysis, RNA, Serine Endopeptidases, Single-Cell Analysis, Virus Internalization},
	issn = {1546-170X},
	doi = {10.1038/s41591-020-01227-z},
	author = {Muus, Christoph and Luecken, Malte D and Eraslan, G{\"o}kcen and Sikkema, Lisa and Waghray, Avinash and Heimberg, Graham and Kobayashi, Yoshihiko and Vaishnav, Eeshit Dhaval and Subramanian, Ayshwarya and Smillie, Christopher and Jagadeesh, Karthik A and Duong, Elizabeth Thu and Fiskin, Evgenij and Triglia, Elena Torlai and Ansari, Meshal and Cai, Peiwen and Lin, Brian and Buchanan, Justin and Chen, Sijia and Jian Shu and Haber, Adam L and Chung, Hattie and Montoro, Daniel T and Adams, Taylor and Aliee, Hananeh and Allon, Samuel J and Andrusivova, Zaneta and Angelidis, Ilias and Ashenberg, Orr and Bassler, Kevin and B{\'e}cavin, Christophe and Benhar, Inbal and Bergenstr{\r a}hle, Joseph and Bergenstr{\r a}hle, Ludvig and Bolt, Liam and Braun, Emelie and Bui, Linh T and Callori, Steven and Chaffin, Mark and Chichelnitskiy, Evgeny and Chiou, Joshua and Conlon, Thomas M and Cuoco, Michael S and Cuomo, Anna S E and Deprez, Marie and Duclos, Grant and Fine, Denise and Fischer, David S and Ghazanfar, Shila and Gillich, Astrid and Giotti, Bruno and Gould, Joshua and Guo, Minzhe and Gutierrez, Austin J and Habermann, Arun C and Harvey, Tyler and He, Peng and Hou, Xiaomeng and Hu, Lijuan and Hu, Yan and Jaiswal, Alok and Ji, Lu and Jiang, Peiyong and Kapellos, Theodoros S and Kuo, Christin S and Larsson, Ludvig and Leney-Greene, Michael A and Lim, Kyungtae and Litvi{\v n}ukov{\'a}, Monika and Ludwig, Leif S and Lukassen, Soeren and Luo, Wendy and Maatz, Henrike and Madissoon, Elo and Mamanova, Lira and Manakongtreecheep, Kasidet and Leroy, Sylvie and Mayr, Christoph H and Mbano, Ian M and McAdams, Alexi M and Nabhan, Ahmad N and Nyquist, Sarah K and Penland, Lolita and Poirion, Olivier B and Poli, Sergio and Qi, CanCan and Queen, Rachel and Reichart, Daniel and Rosas, Ivan and Schupp, Jonas C and Shea, Conor V and Shi, Xingyi and Sinha, Rahul and Sit, Rene V and Slowikowski, Kamil and Slyper, Michal and Smith, Neal P and Sountoulidis, Alex and Strunz, Maximilian and Sullivan, Travis B and Sun, Dawei and Talavera-L{\'o}pez, Carlos and Tan, Peng and Tantivit, Jessica and Travaglini, Kyle J and Tucker, Nathan R and Vernon, Katherine A and Wadsworth, Marc H and Waldman, Julia and Wang, Xiuting and Xu, Ke and Yan, Wenjun and Zhao, William and Ziegler, Carly G K and NHLBI LungMap Consortium and Human Cell Atlas Lung Biological Network}
}
@article {1603874,
	title = {Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes},
	journal = {J Am Soc Nephrol},
	year = {2021},
	month = {2021 Jul 14},
	abstract = {BACKGROUND: Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of end stage kidney disease (ESKD) in individuals with type 1 diabetes at advanced kidney disease stage. METHODS: Gene-based exome array analysis of 15,449 genes in 5 large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time-to-ESKD, testing the top gene in a 6th cohort (N=2,372/1,115 events all cohorts) and replicating in two retrospective case-control studies (N=1,072 cases, 752 controls). Deep resequencing of the top associated gene in 5 cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models. RESULTS: Protein coding variants in the hydroxysteroid 17-beta dehydrogenase 14 gene (HSD17B14), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance (N=4,196; p-value=3.3x10-7). The HSD17B14 gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed HSD17B14 gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other chronic kidney disease-associated renal pathologies. CONCLUSIONS: HSD17B14 gene is mechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.},
	issn = {1533-3450},
	doi = {10.1681/ASN.2020101457},
	author = {Mychaleckyj, Josyf and Valo, Erkka and Ichimura, Takaharu and Ahluwalia, Tarunveer and Dina, Christian and Rachel Miller and Shabalin, Ivan and Gyorgy, Beata and Cao, Jingjing and Onengut-Gumuscu, Suna and Satake, Eiichiro and Smiles, Adam and Haukka, Jani and Tregouet, David-Alexandre and Costacou, Tina and O{\textquoteright}Neil, Kristina and Paterson, Andrew and Forsblom, Carol and Keenan, Hillary and Pezzolesi, Marcus and Pragnell, Marlon and Galecki, Andrzej and Rich, Stephen and Sandholm, Niina and Klein, Ronald and Klein, Barbara and Susztak, Katalin and Orchard, Trevor and Korstanje, Ron and King, George and Hadjadj, Samy and Rossing, Peter and Bonventre, Joseph and Groop, Per-Henrik and Warram, James and Krolewski, Andrzej}
}
@article {1664976,
	title = {Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy},
	journal = {Hum Mol Genet},
	volume = {32},
	number = {3},
	year = {2023},
	month = {2023 Jan 13},
	pages = {431-449},
	abstract = {Usher syndrome (USH) is the most common form of hereditary deaf-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinae uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in M{\"u}ller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones and outer segments (OS) of rods as well as at adhesive junctions between MGCs and photoreceptor cells (PRCs) in the outer limiting membrane (OLM). Our data provide evidence for the interaction of harmonin with OLM molecules in PRCs and MGCs and rhodopsin in PRCs. Subcellular expression and colocalization of harmonin correlate with the clinical phenotype observed in USH1C patients. We also demonstrate that primary cilia defects in USH1C patient-derived fibroblasts could be reverted by the delivery of harmonin_a1 transcript isoform. Our studies thus provide novel insights into PRC cell biology, USH1C pathophysiology and development of gene therapy treatment(s).},
	keywords = {Cell Cycle Proteins, Cytoskeletal Proteins, Humans, Photoreceptor Cells, Retina, Usher Syndromes},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddac211},
	author = {Nagel-Wolfrum, Kerstin and Fadl, Benjamin R and Becker, Mirjana M and Wunderlich, Kirsten A and Sch{\"a}fer, Jessica and Sturm, Daniel and Fritze, Jacques and G{\"u}r, Burcu and Kaplan, Lew and Andreani, Tommaso and Goldmann, Tobias and Brooks, Matthew and Starostik, Margaret R and Lokhande, Anagha and Apel, Melissa and Fath, Karl R and Stingl, Katarina and Kohl, Susanne and Deangelis, Margaret M and Schl{\"o}tzer-Schrehardt, Ursula and Kim, Ivana K and Owen, Leah A and Vetter, Jan M and Pfeiffer, Norbert and Andrade-Navarro, Miguel A and Grosche, Antje and Swaroop, Anand and Wolfrum, Uwe}
}
@article {742281,
	title = {Orbital exenteration: The 10-year Massachusetts Eye and Ear Infirmary experience.},
	journal = {Orbit},
	volume = {35},
	number = {4},
	year = {2016},
	month = {2016 Aug},
	pages = {199-206},
	abstract = {The authors report their experience with orbital exenteration surgery at one academic institution over a 10-year period and review the literature. This retrospective cohort study monitored outcomes of all patients who underwent orbital exenteration surgery at Massachusetts Eye and Ear Infirmary between January 2003 and January 2013. Patients with no follow-up data or survival data were excluded from the study. The main outcome measures were surgical complications, disease status of surgical margins, need for adjuvant treatment, local recurrence, metastases and survival. 23 patients with malignancy and 2 with mucormycosis met inclusion criteria for the study. Surgical procedures included non-lid sparing total exenteration (44\%), lid-sparing total exenteration (32\%), non-lid sparing partial exenteration (8\%) and lid-sparing partial exenteration (16\%). 44\% underwent additional extra-orbital procedures. Survival rates were 72\% at 1 year, 48\% at 3 years, and 37\% at 5 years. Of patients with malignancies, 48\% had clear margins after exenteration. There was no statistically significant difference in survival between patients with negative surgical margins compared to positive margins (p = 0.12). Mortality was highest in patients with melanoma (85.7\%) and lowest in patients with non-squamous cell lid malignancies (0\%). Our study suggests that the type of disease has a much greater impact on the survival of patients undergoing exenteration surgery than the type of exenteration surgery or the disease status of surgical margins. Patients with non-squamous cell lid malignancies and localized orbital disease have the best prognosis for tumor eradication from this radical and highly disfiguring surgery.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2016.1176210},
	author = {Nagendran, Sonali T and Lee, N Grace and Fay, Aaron and Lefebvre, Daniel R and Sutula, Francis C and Freitag, Suzanne K}
}
@article {1688336,
	title = {Symptom-based stratification algorithm for heterogeneous symptoms of dry eye disease: a feasibility study},
	journal = {Eye (Lond)},
	volume = {37},
	number = {16},
	year = {2023},
	month = {2023 Nov},
	pages = {3484-3491},
	abstract = {BACKGROUND/OBJECTIVE: To test the feasibility of a dry eye disease (DED) symptom stratification algorithm previously established for the general population among patients visiting ophthalmologists. SUBJECT/METHODS: This retrospective cross-sectional study was conducted between December 2015 and October 2021 at a university hospital in Japan; participants who underwent a comprehensive DED examination and completed the Japanese version of the Ocular Surface Disease Index (J-OSDI) were included. Patients diagnosed with DED were stratified into seven clusters using a previously established symptom-based stratification algorithm for DED. Characteristics of the patients in stratified clusters were compared. RESULTS: In total, 426 participants were included (median age [interquartile range]; 63 [48-72] years; 357 (83.8\%) women). Among them, 291 (68.3\%) participants were diagnosed with DED and successfully stratified into seven clusters. The J-OSDI total score was highest in cluster 1 (61.4 [52.2-75.0]), followed by cluster 5 (44.1 [38.8-47.9]). The tear film breakup time was the shortest in cluster 1 (1.5 [1.1-2.1]), followed by cluster 3 (1.6 [1.0-2.5]). The J-OSDI total scores from the stratified clusters in this study and those from the clusters identified in the previous study showed a significant correlation (r = 0.991, P \&lt; 0.001). CONCLUSIONS: The patients with DED who visited ophthalmologists were successfully stratified by the previously established algorithm for the general population, uncovering patterns for their seemingly heterogeneous and variable clinical characteristics of DED. The results have important implications for promoting treatment interventions tailored to individual patients and implementing smartphone-based clinical data collection in the future.},
	keywords = {Cross-Sectional Studies, Dry Eye Syndromes, Feasibility Studies, Female, Humans, Male, Retrospective Studies, Smartphone, Tears},
	issn = {1476-5454},
	doi = {10.1038/s41433-023-02538-4},
	author = {Nagino, Ken and Inomata, Takenori and Nakamura, Masahiro and Sung, Jaemyoung and Midorikawa-Inomata, Akie and Iwagami, Masao and Fujio, Kenta and Akasaki, Yasutsugu and Okumura, Yuichi and Huang, Tianxiang and Fujimoto, Keiichi and Eguchi, Atsuko and Miura, Maria and Hurramhon, Shokirova and Zhu, Jun and Ohno, Mizu and Hirosawa, Kunihiko and Morooka, Yuki and Dana, Reza and Murakami, Akira and Kobayashi, Hiroyuki}
}
@article {1623347,
	title = {Parental Trust in School-Based Health Care: A Systematic Review},
	journal = {J Sch Health},
	volume = {92},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {79-91},
	abstract = {BACKGROUND: Health care delivery in schools is a frequently adopted approach to reduce health care inequalities. Lack of parental trust has been identified as impacting participation in school-based health care programs (SBHPs). The aim of our systematic review is to outline themes related to parental trust in SBHPs. METHODS: We searched MEDLINE, Embase, CINHAL, ERIC, PsycInfo, and Web of Science for articles published between 1969 and 2019. Eligible studies (1) were peer-reviewed primary research articles; (2) were school-based health interventions or screening programs; (3) included parental trust data; and (4) were carried out on schoolchildren from pre-K to grade 12. Study location, data collection date, number of participants, demographics, intervention type, study aim and methodology, and all trust themes mentioned, were extracted. Studies were critically appraised using the CASP checklist for qualitative research. RESULTS: We identified 9 themes related to parental trust in SBHPs: (1) safety; (2) effectiveness; (3) health professionals{\textquoteright} training and credentials; (4) communication; (5) confidentiality; (6) providers; (7) government, authorities, and health service; (8) the pharmaceutical industry; and (9) research and data sharing. CONCLUSIONS: The themes identified provide a framework for examining trust in SBHPs, and may guide the development of interventions to increase trust and engagement in SBHPs.},
	issn = {1746-1561},
	doi = {10.1111/josh.13106},
	author = {Nahum, Andrea S and Vongsachang, Hursuong and Friedman, David S and Collins, Megan E}
}
@article {1559571,
	title = {Prevalence and causes of vision loss in sub-Saharan Africa in 2015: magnitude, temporal trends and projections},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {1658-1668},
	abstract = {BACKGROUND: This study aimed to assess the prevalence and causes of vision loss in sub-Saharan Africa (SSA) in 2015, compared with prior years, and to estimate expected values for 2020. METHODS: A systematic review and meta-analysis assessed the prevalence of blindness (presenting distance visual acuity \&lt;3/60 in the better eye), moderate and severe vision impairment (MSVI; presenting distance visual acuity \&lt;6/18 but >=3/60) and mild vision impairment (MVI; presenting distance visual acuity \&lt;6/12 and >=6/18), and also near vision impairment (},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-315217},
	author = {Naidoo, Kovin and Kempen, John H and Gichuhi, Stephen and Braithwaite, Tasanee and Casson, Robert J and Cicinelli, Maria Vittoria and Das, Aditi and Flaxman, Seth R and Jonas, Jost B and Keeffe, Jill Elizabeth and Leasher, Janet and Limburg, Hans and Pesudovs, Konrad and Resnikoff, Serge and Silvester, Alexander J and Tahhan, Nina and Taylor, Hugh R and Wong, Tien Y and Bourne, Rupert R A and Vision Loss Expert Group of the Global Burden of Disease Study}
}
@article {1667696,
	title = {A Novel Murine Model of Endothelial Keratoplasty},
	journal = {Cornea},
	volume = {42},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {224-231},
	abstract = {PURPOSE: The purpose of this study was to establish a murine model of endothelial keratoplasty. METHODS: Endothelial keratoplasty (EK) was performed using C57BL/6 donor and BALB/c recipient mice. The central endothelium and Descemet membrane were removed from the recipient cornea, and a 1.5-mm posterior lamellar donor graft was made adherent to the recipient cornea with a small amount of viscoelastic. Mice were followed through slitlamp microscopy postoperatively, and OCT was used to assess the cornea and anterior chamber and measure central corneal thickness. Histology and immunohistochemistry were performed to confirm graft adherence and endothelial cell morphology. RESULTS: Successfully attached EK grafts were visualized in all transplanted animals. Histology and immunostaining confirmed proper graft orientation and adherence, as well as the presence of donor endothelium on transplanted grafts. We observed maximal corneal edema in all animals at day 1 postoperatively which gradually subsided. EK graft survival was 97\% at 8 weeks. CONCLUSIONS: In this study, we describe a novel murine model for EK which we anticipate will enable detailed investigation into the cellular and molecular mechanisms involved in EK pathobiology.},
	keywords = {Animals, Cornea, Corneal Transplantation, Descemet Stripping Endothelial Keratoplasty, Disease Models, Animal, Endothelium, Corneal, Mice, Mice, Inbred C57BL},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003047},
	author = {Nakagawa, Hayate and Blanco, Tomas and Kahale, Francesca and Wang, Shudan and Musayeva, Aytan and Alemi, Hamid and Dohlman, Thomas H and Dana, Reza}
}
@article {1688301,
	title = {Descemet Stripping Only Technique for Corneal Endothelial Damage in Mice},
	journal = {Cornea},
	volume = {42},
	number = {4},
	year = {2023},
	month = {2023 Apr 01},
	pages = {470-475},
	abstract = {PURPOSE: Descemet stripping only is an emerging surgical technique used to remove central Descemet membrane and corneal endothelial cells in patients with corneal endothelial disease. Here, we describe a murine model of this procedure to help facilitate basic science investigation and evaluation of postoperative outcomes using this surgical technique. METHODS: Slitlamp biomicroscopy, central corneal thickness assessment (by optical coherence tomography), and immunohistochemistry were used to assess the model through 7 weeks of follow-up. RESULTS: Complete removal of the endothelium and Descemet membrane was confirmed by slitlamp biomicroscopy and by histology. Central corneal thickness peaked at day 1 postinjury and then declined over the course of 2 weeks to a stable level of persistent edema. Seven weeks postinjury, immunohistochemical staining for ZO-1 showed the area of Descemet stripping was fully covered by enlarged and dysmorphic corneal endothelial cell. No significant ocular complications were appreciated through the end of the follow-up. CONCLUSIONS: We demonstrate the feasibility of and provide detailed instructions for a murine model of Descemet stripping only. This model provides a potential in vivo platform to investigate the mechanisms and biology of this emerging surgical procedure.},
	keywords = {Animals, Corneal Diseases, Corneal Injuries, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Disease Models, Animal, Endothelial Cells, Endothelium, Corneal, Mice},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003223},
	author = {Nakagawa, Hayate and Alemi, Hamid and Wang, Shudan and Kahale, Francesca and Blanco, Tomas and Liu, Catherine and Yin, Jia and Dohlman, Thomas H and Dana, Reza}
}
@article {1661603,
	title = {Machine Learning Prediction of Adenovirus D8 Conjunctivitis Complications from Viral Whole-Genome Sequence},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {4},
	year = {2022},
	month = {2022 Dec},
	pages = {100166},
	abstract = {OBJECTIVE: To obtain complete DNA sequences of adenoviral (AdV) D8 genome from patients with conjunctivitis and determine the relation of sequence variation to clinical outcomes. DESIGN: This study is a post hoc analysis of banked conjunctival swab samples from the BAYnovation Study, a previously conducted, randomized controlled clinical trial for AdV conjunctivitis. PARTICIPANTS: Ninety-six patients with AdV D8-positive conjunctivitis who received placebo treatment in the BAYnovation Study were included in the study. METHODS: DNA from conjunctival swabs was purified and subjected to whole-genome viral DNA sequencing. Adenovirus D8 variants were identified and correlated with clinical outcomes, including 2 machine learning methods. MAIN OUTCOME MEASURES: Viral DNA sequence and development of subepithelial infiltrates (SEIs) were the main outcome measures. RESULTS: From initial sequencing of 80 AdV D8-positive samples, full adenoviral genome reconstructions were obtained for 71. A total of 630 single-nucleotide variants were identified, including 156 missense mutations. Sequence clustering revealed 3 previously unappreciated viral clades within the AdV D8 type. The likelihood of SEI development differed significantly between clades, ranging from 83\% for Clade 1 to 46\% for Clade 3. Genome-wide analysis of viral single-nucleotide polymorphisms failed to identify single-gene determinants of outcome. Two machine learning models were independently trained to predict clinical outcome using polymorphic sequences. Both machine learning models correctly predicted development of SEI outcomes in a newly sequenced validation set of 16 cases (P = 1.5\&nbsp;{\texttimes}\&nbsp;10-5). Prediction was dependent on ensemble groups of polymorphisms across multiple genes. CONCLUSIONS: Adenovirus D8 has >= 3 prevalent molecular substrains, which differ in propensity to result in SEIs. Development of SEIs can be accurately predicted from knowledge of full viral sequence. These results suggest that development of SEIs in AdV D8 conjunctivitis is largely attributable to pathologic viral sequence variants within the D8 type and establishes machine learning paradigms as a powerful technique for understanding viral pathogenicity.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100166},
	author = {Nakamichi, Kenji and Akileswaran, Lakshmi and Meirick, Thomas and Lee, Michele D and Chodosh, James and Rajaiya, Jaya and Stroman, David and Wolf-Yadlin, Alejandro and Jackson, Quinn and Holtz, W Bradley and Lee, Aaron Y and Lee, Cecilia S and Van Gelder, Russell N and BAYnovation Study Group}
}
@article {1661814,
	title = {Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice},
	journal = {Transplantation},
	volume = {107},
	number = {6},
	year = {2023},
	month = {2023 Jun 01},
	pages = {1302-1310},
	abstract = {BACKGROUND: Corneal transplantation outcomes are generally less favorable in young children compared with adults. The purpose of this study was to determine the immunological mechanisms underlying this difference. METHODS: A murine model of allogeneic corneal transplantation was used in the study, and graft survival was determined by evaluating opacity scores for 8 wk. Syngeneic transplantation in the very young host served as a surgical control. The frequencies of total and activated natural killer (NK) cells in cornea posttransplantation were kinetically evaluated using flow cytometry. The regulatory T cell (Treg) frequency and function in naive animals were assessed by flow cytometry and in vitro suppression assays, respectively. Finally, graft survival and immune responses were determined in NK cell-depleted, or adult naive Treg-transferred, young hosts. RESULTS: Corneal allograft survival in the very young recipients was significantly lower than in adult hosts. The frequencies of total NK cells and their interferon gamma-expressing subset in the cornea were significantly higher in the very young mice posttransplantation. In ungrafted mice, frequencies of Treg in draining lymph nodes as well as their capabilities to suppress NK-cell secretion of interferon gamma were lower in the very young compared with adults. In NK cell-depleted or adult Treg--transferred very young recipients, the allograft survival was significantly improved along with the suppressed NK-cell response. CONCLUSIONS: Our data demonstrate that amplified activity of NK cells, together with lower suppressive function of Treg, contributes to early rejection of corneal allografts in very young graft recipients.},
	keywords = {Animals, Cornea, Corneal Transplantation, Graft Rejection, Interferon-gamma, Killer Cells, Natural, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, T-Lymphocytes, Regulatory},
	issn = {1534-6080},
	doi = {10.1097/TP.0000000000004424},
	author = {Nakao, Takeshi and Inomata, Takenori and Blanco, Tomas and Musayeva, Aytan and Tahvildari, Maryam and Amouzegar, Afsaneh and Yin, Jia and Chauhan, Sunil K and Chen, Yihe and Dana, Reza}
}
@article {1677661,
	title = {Artificial intelligence in uveitis: A comprehensive review},
	journal = {Surv Ophthalmol},
	volume = {68},
	number = {4},
	year = {2023},
	month = {2023 Jul-Aug},
	pages = {669-677},
	abstract = {Uveitis is a disease complex characterized by intraocular inflammation of the uvea that is an important cause of blindness and social morbidity. With the dawn of artificial intelligence (AI) and machine learning integration in health care, their application in uveitis creates an avenue to improve screening and diagnosis. Our review identified the use of artificial intelligence in studies of uveitis and classified them as diagnosis support, finding detection, screening, and standardization of uveitis nomenclature. The overall performance of models is poor, with limited datasets and a lack of validation studies and publicly available data and codes. We conclude that AI holds great promise to assist with the diagnosis and detection of ocular findings of uveitis, but further studies and large representative datasets are needed to guarantee generalizability and fairness.},
	keywords = {Artificial Intelligence, Delivery of Health Care, Humans, machine learning, Uvea, Uveitis},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2023.02.007},
	author = {Nakayama, Luis F and Ribeiro, Lucas Z and Dychiao, Robyn G and Zamora, Yuslay F and Regatieri, Caio V S and Celi, Leo A and Silva, Paolo and Sobrin, Lucia and Belfort, Rubens}
}
@article {1360116,
	title = {Prevalence and causes of blindness and vision impairment: magnitude, temporal trends and projections in South and Central Asia},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {7},
	year = {2019},
	month = {2019 Jul},
	pages = {871-877},
	abstract = {BACKGROUND: To assess prevalence and causes of vision loss in Central and South Asia. METHODS: A systematic review of medical literature assessed the prevalence of blindness (presenting visual acuity\&lt;3/60 in the better eye), moderate and severe vision impairment (MSVI; presenting visual acuity \&lt;6/18 but >=3/60) and mild vision impairment (MVI; presenting visual acuity \&lt;6/12 and >=6/18) in Central and South Asia for 1990, 2010, 2015 and 2020. RESULTS: In Central and South Asia combined, age-standardised prevalences of blindness, MSVI and MVI in 2015 were for men and women aged 50+years, 3.72\% (80\% uncertainty interval (UI): 1.39-6.75) and 4.00\% (80\% UI: 1.41-7.39), 16.33\% (80\% UI: 8.55-25.47) and 17.65\% (80\% UI: 9.00-27.62), 11.70\% (80\% UI: 4.70-20.32) and 12.25\% (80\% UI:4.86-21.30), respectively, with a significant decrease in the study period for both gender. In South Asia in 2015, 11.76 million individuals (32.65\% of the global blindness figure) were blind and 61.19 million individuals (28.3\% of the global total) had MSVI. From 1990 to 2015, cataract (accounting for 36.58\% of all cases with blindness in 2015) was the most common cause of blindness, followed by undercorrected refractive error (36.43\%), glaucoma (5.81\%), age-related macular degeneration (2.44\%), corneal diseases (2.43\%), diabetic retinopathy (0.16\%) and trachoma (0.04\%). For MSVI in South Asia 2015, most common causes were undercorrected refractive error (accounting for 66.39\% of all cases with MSVI), followed by cataract (23.62\%), age-related macular degeneration (1.31\%) and glaucoma (1.09\%). CONCLUSIONS: One-third of the global blind resided in South Asia in 2015, although the age-standardised prevalence of blindness and MSVI decreased significantly between 1990 and 2015.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-312292},
	author = {Nangia, Vinay and Jonas, Jost B and George, Ronnie and Lingam, Vijaya and Ellwein, Leon and Cicinelli, Maria Vittoria and Das, Aditi and Flaxman, Seth R and Keeffe, Jill E and Kempen, John H and Leasher, Janet and Limburg, Hans and Naidoo, Kovin and Pesudovs, Konrad and Resnikoff, Serge and Silvester, Alexander J and Tahhan, Nina and Taylor, Hugh R and Wong, Tien Y and Bourne, Rupert R A and Vision Loss Expert Group of the Global Burden of Disease Study}
}
@article {1635625,
	title = {Computed tomography and [18F]-FDG PET imaging provide additional readouts for COVID-19 pathogenesis and therapies evaluation in non-human primates},
	journal = {iScience},
	volume = {25},
	number = {4},
	year = {2022},
	month = {2022 Apr 15},
	pages = {104101},
	abstract = {Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool for monitoring infection in this species. We investigated the benefit of computed X-ray tomography (CT) and [18F]-FDG positron emission tomography (PET) to monitor the early phase of the disease in a large cohort (n\&nbsp;= 76) of SARS-CoV-2 infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at the acute phase reflect the heterogeneity of lung burden following infection. Moreover, [18F]-FDG PET revealed that FDG uptake was significantly higher in the lungs, nasal cavities, lung-draining lymph nodes, and spleen of NHPs by 5\&nbsp;days postinfection compared to pre-infection levels, indicating early local inflammation. The comparison of CT and PET data from previous COVID-19 treatments or vaccines we tested in NHP, to this large cohort of untreated animals demonstrated the value of in\&nbsp;vivo imaging in preclinical trials.},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2022.104101},
	author = {Naninck, Thibaut and Kahlaoui, Nidhal and Lemaitre, Julien and Maisonnasse, Pauline and De Mori, Antoine and Pascal, Quentin and Contreras, Vanessa and Marlin, Romain and Relouzat, Francis and Delache, Beno{\^\i}t and H{\'e}rate, C{\'e}cile and Aldon, Yoann and van Gils, Marit and Zabaleta, Nerea and Tsong Fang, Rapha{\"e}l Ho and Bosquet, Nathalie and Sanders, Rogier W and Vandenberghe, Luk H and Chapon, Catherine and Le Grand, Roger}
}
@article {1323937,
	title = {In Response},
	journal = {Anesth Analg},
	volume = {127},
	number = {4},
	year = {2018},
	month = {2018 Oct},
	pages = {e69-e70},
	issn = {1526-7598},
	doi = {10.1213/ANE.0000000000003658},
	author = {Nanji, Karen C and Fain, Barbara and Morley, Michael G and Bayes, Joseph}
}
@article {1213836,
	title = {Preventing Adverse Events in Cataract Surgery: Recommendations From a Massachusetts Expert Panel},
	journal = {Anesth Analg},
	volume = {126},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {1537-1547},
	abstract = {Massachusetts health care facilities reported a series of cataract surgery-related adverse events (AEs) to the state in recent years, including 5 globe perforations during eye blocks performed by 1 anesthesiologist in a single day. The Betsy Lehman Center for Patient Safety, a nonregulatory Massachusetts state agency, responded by convening an expert panel of frontline providers, patient safety experts, and patients to recommend strategies for mitigating patient harm during cataract surgery. The purpose of this article is to identify contributing factors to the cataract surgery AEs reported in Massachusetts and present the panel{\textquoteright}s recommended strategies to prevent them. Data from state-mandated serious reportable event reports were supplemented by online surveys of Massachusetts cataract surgery providers and semistructured interviews with key stakeholders and frontline staff. The panel identified 2 principal categories of contributing factors to the state{\textquoteright}s cataract surgery-related AEs: systems failures and choice of anesthesia technique. Systems failures included inadequate safety protocols (48.7\% of contributing factors), communication challenges (18.4\%), insufficient provider training (17.1\%), and lack of standardization (15.8\%). Choice of anesthesia technique involved the increased relative risk of needle-based eye blocks. The panel{\textquoteright}s surveys of Massachusetts cataract surgery providers show wide variation in anesthesia practices. While 45.5\% of surgeons and 69.6\% of facilities reported increased use of topical anesthesia compared to 10 years earlier, needle-based blocks were still used in 47.0\% of cataract surgeries performed by surgeon respondents and 40.9\% of those performed at respondent facilities. Using a modified Delphi approach, the panel recommended several strategies to prevent AEs during cataract surgery, including performing a distinct time-out with at least 2 care-team members before block administration; implementing standardized, facility-wide safety protocols, including a uniform site-marking policy; strengthening the credentialing and orientation of new, contracted and locum tenens anesthesia staff; ensuring adequate and documented training in block administration for any provider who is new to a facility, including at least 10 supervised blocks before practicing independently; using the least invasive form of anesthesia appropriate to the patient; and finally, adjusting anesthesia practices, including preferred techniques, as evidence-based best practices evolve. Future research should focus on evaluating the impact of these recommendations on patient outcomes.},
	issn = {1526-7598},
	doi = {10.1213/ANE.0000000000002529},
	author = {Nanji, Karen C and Roberto, Sarah A and Morley, Michael G and Bayes, Joseph}
}
@article {1347441,
	title = {In Response},
	journal = {Anesth Analg},
	volume = {128},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {e11-e12},
	issn = {1526-7598},
	doi = {10.1213/ANE.0000000000003872},
	author = {Nanji, Karen C and Fain, Barbara and Morley, Michael G and Bayes, Joseph}
}
@article {1323936,
	title = {In Response},
	journal = {Anesth Analg},
	volume = {127},
	number = {4},
	year = {2018},
	month = {2018 Oct},
	pages = {e67-e68},
	issn = {1526-7598},
	doi = {10.1213/ANE.0000000000003656},
	author = {Nanji, Karen C and Fain, Barbara and Morley, Michael G and Bayes, Joseph}
}
@article {1698316,
	title = {Macular dystrophy with associated retinitis pigmentosa-1 like 1 genetic mutation},
	journal = {Clin Exp Optom},
	year = {2023},
	month = {2023 May 08},
	pages = {1-3},
	issn = {1444-0938},
	doi = {10.1080/08164622.2023.2205013},
	author = {Nano, Eni and Baskin, Elina and Greenberg, Paul B and Huckfeldt, Rachel M and Hunter, Amanda}
}
@article {1538336,
	title = {An exploratory study to evaluate visual function endpoints in non-advanced age-related macular degeneration},
	journal = {BMC Ophthalmol},
	volume = {20},
	number = {1},
	year = {2020},
	month = {2020 Oct 22},
	pages = {424},
	abstract = {BACKGROUND: To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD. METHODS: A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1-4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF{\texttrademark} test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated. RESULTS: There was no difference in standard ETDRS VA between non-advanced AMD (0.06 {\textpm} 0.02 logMAR) and normal groups (0.04 {\textpm} 0.02 logMAR) (p = 0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p \&gt; 0.05). Ora-VCF{\texttrademark} test was significantly worse in the non-advanced AMD group compared to normals (0.67 {\textpm} 0.07 in AMD; 0.45 {\textpm} 0.04 in normals, p = 0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55 {\textpm} 11.22 wpm in AMD; 145.17 {\textpm} 9.55 wpm in normals p = 0.049). No significant difference between the groups was noted using other tests. Repeatability was 82\% for Ora-VCF{\texttrademark} test and 92\% for Ora-tablet LL 2.0ND reading. Reproducibility was 89\% for both Ora-VCF{\texttrademark} test and Ora-tablet LL 2.0ND reading. CONCLUSION: While there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF{\texttrademark} test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.},
	issn = {1471-2415},
	doi = {10.1186/s12886-020-01683-8},
	author = {Narayanan, Divya and Rodriguez, John and Wallstrom, Garrick and Welch, Donna and Chapin, Matthew and Arrigg, Paul and Abelson, Mark}
}
@article {1532344,
	title = {Early Ophthalmic Changes in Macula Does Not Correlate with Visual Function},
	journal = {Clin Ophthalmol},
	volume = {14},
	year = {2020},
	month = {2020},
	pages = {2571-2576},
	abstract = {Purpose: Early detection and treatment of age-related macular degeneration require a clear understanding of the early progress of the disease. The purpose of this study was to investigate whether minimal macular ophthalmoscopic changes corresponded to changes in visual function. Methods: Color macular photos from a group of older subjects who were classified as grade 0 on AREDS simplified grading were further evaluated by a retinal specialist using 5x magnification for possible minimal macular anomalies. Group 0-A ( = 15) were defined as subjects with no visible macular anomalies while Group 0-B ( = 19) comprised subjects for whom minimal macular mottling, pigment changes or very small drusen (\&lt; 63 {\textmu}m) were observed in the study eye. All subjects had best VA of 20/25 or better and had no evidence of other retinal diseases in the study eye. All subjects underwent a series of visual function tests such as standard ETDRS VA, low luminance ETDRS VA, Pelli-Robson contrast sensitivity, variable contrast flicker (VCF) sensitivity, and reading speed (words per minute, wpm) using both MNRead and low luminance reading on a tablet. Results: There was no significant difference between the mean age between the two groups (74.8 {\textpm} 5.2 years for 0-A vs 74.5 {\textpm} 4.4 for 0-B, = 0.82). None of the visual function tests identified any significant difference between the two groups. Mean ETDRS VA was 0.0 {\textpm} 0.11 for 0-A subjects and 0.08 {\textpm} 0.12 for 0-B ( = 0.063). Mean Pelli-Robson log contrast sensitivity was 1.75 {\textpm} 0.29 for 0-A and 1.78 {\textpm} 0.17 for the 0-B group ( = 0.73). VCF threshold was 0.47 {\textpm} 0.25 for 0-A and 0.43 {\textpm} 0.22 for 0-B ( = 0.64). Reading speed using MNRead was 214 {\textpm} 47.4 wpm for 0-A and 210 {\textpm} 64.7 for 0-B ( = 0.85). Low luminance tablet reading speed was 137 {\textpm} 71.8 wpm for 0-A and 151 {\textpm} 39.4 (0-B) ( = 0.49). Conclusion: A panel of psychophysical tests did not demonstrate significant differences between subjects with and without minimal macular changes.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S260787},
	author = {Narayanan, Divya and Wallstrom, Garrick and Rodriguez, John and Welch, Donna and Chapin, Matthew and Arrigg, Paul and Patil, Rajkumar and Abelson, Mark}
}
@article {1522736,
	title = {Visual search errors are persistent in a laboratory analog of the incidental finding problem},
	journal = {Cogn Res Princ Implic},
	volume = {5},
	number = {1},
	year = {2020},
	month = {2020 Jul 29},
	pages = {32},
	abstract = {When radiologists search for a specific target (e.g., lung cancer), they are also asked to report any other clinically significant "incidental findings" (e.g., pneumonia). These incidental findings are missed at an undesirably high rate. In an effort to understand and reduce these errors, Wolfe et al. (Cognitive Research: Principles and Implications 2:35, 2017) developed "mixed hybrid search" as a model system for incidental findings. In this task, non-expert observers memorize six targets: half of these targets are specific images (analogous to the suspected diagnosis in the clinical task). The other half are broader, categorically defined targets, like "animals" or "cars" (analogous to the less well-specified incidental findings). In subsequent search through displays for any instances of any of the targets, observers miss about one third of the categorical targets, mimicking the incidental finding problem. In the present paper, we attempted to reduce the number of errors in the mixed hybrid search task with the goal of finding methods that could be deployed in a clinical setting. In Experiments 1a and 1b, we reminded observers about the categorical targets by inserting non-search trials in which categorical targets were clearly marked. In Experiment 2, observers responded twice on each trial: once to confirm the presence or absence of the specific targets, and once to confirm the presence or absence of the categorical targets. In Experiment 3, observers were required to confirm the presence or absence of every target on every trial using a checklist procedure. Only Experiment 3 produced a marked decline in categorical target errors, but at the cost of a substantial increase in response time.},
	issn = {2365-7464},
	doi = {10.1186/s41235-020-00235-4},
	author = {Nartker, Makaela S and Alaoui-Soce, Abla and Wolfe, Jeremy M}
}
@article {1263371,
	title = {Identification of the Infection Source of an Outbreak of Mycobacterium Chelonae Keratitis After Laser in Situ Keratomileusis},
	journal = {Cornea},
	volume = {37},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {116-122},
	abstract = {PURPOSE: Nontuberculous mycobacteria keratitis is a rare but challenging complication of laser in situ keratomileusis (LASIK). This study was conducted to determine the source(s) of infection in a cluster of cases of keratitis after LASIK and to describe this outbreak and patients{\textquoteright} outcomes. METHODS: In this retrospective, case series, single-center study, 86 patients were included who underwent LASIK or photorefractive keratectomy between December 2011 and February 2012. Corneal scrapes from the affected eyes, samples of tap and distilled water, water from the reservoir of the distilling equipment, steamer, and autoclave cassette; antiseptic and anesthetic solutions and surgical instrument imprints were cultivated in liquid and on solid media. Gram-negative bacteria and yeasts were identified using automated systems and mycobacteria by polymerase chain reaction-restriction enzyme analysis of the hsp65 gene (PRA-hsp65) and DNA sequencing. Mycobacterial isolates were typed by pulsed-field gel electrophoresis. The cases and outcomes are described. The main outcome measure was identification of the source(s) of the mycobacterial infections. RESULTS: Eight (15 eyes) of 86 patients (172 eyes) who underwent LASIK developed infections postoperatively; no patients who underwent photorefractive keratectomy developed infections. Mycobacterium chelonae was isolated from 4 eyes. The distilled water collected in the surgical facility contained the same M. chelonae strain isolated from the patients{\textquoteright} eyes. Different gram-negative bacteria and yeasts were isolated from samples collected at the clinic but not from the patients{\textquoteright} eyes. CONCLUSIONS: Tap water distilled locally in surgical facilities may be a source of infection after ocular surgery and its use should be avoided.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001423},
	author = {Nascimento, Heloisa and Viana-Niero, Cristina and Nogueira, Christiane Louren{\c c}o and Martins Bispo, Paulo Jos{\'e} and Pinto, Fernando and de Paula Pereira Uzam, Camila and Matsumoto, Cristianne Kayoko and Oliveira Machado, Ant{\^o}nia Maria and Le{\~a}o, Sylvia Cardoso and H{\"o}fling-Lima, Ana Luisa and de Freitas, Denise}
}
@article {647341,
	title = {Corneal Patch Graft: A New Approach for Scleral Necrosis Secondary to Plaque Radiotherapy.},
	journal = {Cornea},
	volume = {35},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {565-8},
	abstract = {PURPOSE: To evaluate the anatomical outcomes of corneal patch grafts in patients with progressive scleral necrosis secondary to plaque radiotherapy used for uveal malignant melanoma management. METHODS: In this case series, 4 patients with progressive scleral necrosis after Ru-106 plaque radiotherapy underwent corneal patch grafts with the anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue to strengthen the sclera and to improve appearance of the eye. RESULTS: Ciliary body involvement was evident in all cases. All 4 patients had received radiation doses of 400 Gy or more to the tumor base. The mean time interval between plaque radiotherapy and scleral necrosis was 24.5 {\textpm} 7.5 months (range, 18-34 months). Successful results were achieved in all patients with tectonic graft. No patients experienced graft thinning, rejection, infection, or tumor recurrence in a mean follow-up of 28.5 {\textpm} 7.9 months (range, 20-39 months). CONCLUSIONS: Corneal patch graft by anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue results in successful restoration of globe integrity and satisfactory cosmetic appearance in patients with scleral necrosis secondary to plaque radiotherapy.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000716},
	author = {Naseripour, Masood and Aghaei, Hossein and Sedaghat, Ahad and Kheirkhah, Ahmad and Jaberi, Ramin and Azma, Zohreh}
}
@article {503971,
	title = {Neuroanatomy goes viral!},
	journal = {Front Neuroanat},
	volume = {9},
	year = {2015},
	month = {2015},
	pages = {80},
	abstract = {The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist{\textquoteright}s toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and extending the range of species that can be studied.},
	issn = {1662-5129},
	doi = {10.3389/fnana.2015.00080},
	author = {Nassi, Jonathan J and Cepko, Constance L and Born, Richard T and Beier, Kevin T}
}
@article {1351173,
	title = {Corticocortical feedback increases the spatial extent of normalization},
	journal = {Front Syst Neurosci},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {105},
	abstract = {Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron{\textquoteright}s driving input and the spatially integrated activity of a "normalization pool." Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing.},
	issn = {1662-5137},
	doi = {10.3389/fnsys.2014.00105},
	author = {Nassi, Jonathan J and G{\'o}mez-Laberge, Camille and Kreiman, Gabriel and Born, Richard T}
}
@article {1363164,
	title = {Ocular graft versus host disease following allogeneic stem cell transplantation: a review of current knowledge and recommendations},
	journal = {J Ophthalmic Vis Res},
	volume = {8},
	number = {4},
	year = {2013},
	month = {2013 Oct},
	pages = {351-8},
	abstract = {Graft versus host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). Ocular GVHD develops in approximately 40-60\% of patients following allo-SCT and its most common clinical manifestations include keratoconjunctivitis sicca and cicatricial conjunctivitis. Ocular GVHD may lead to severe ocular surface disease, which can significantly diminish quality of life and restrict daily activities. It is thus important to monitor the condition closely since with timely diagnosis, irreversible damage can be avoided. The current review will focus on updated information regarding ocular GVHD.},
	issn = {2008-2010},
	author = {Nassiri, Nariman and Eslani, Medi and Panahi, Nekoo and Mehravaran, Shiva and Ziaei, Alireza and Djalilian, Ali R}
}
@article {1629472,
	title = {Recessive variants in COL25A1 gene as novel cause of arthrogryposis multiplex congenita with ocular congenital cranial dysinnervation disorder},
	journal = {Hum Mutat},
	volume = {43},
	number = {4},
	year = {2022},
	month = {2022 Apr},
	pages = {487-498},
	abstract = {A proper interaction between muscle-derived collagen XXV and its motor neuron-derived receptors protein tyrosine phosphatases σ and δ (PTP σ/δ) is indispensable for intramuscular motor innervation. Despite this, thus far, pathogenic recessive variants in the COL25A1 gene had only been detected in a few patients with isolated ocular congenital cranial dysinnervation disorders. Here we describe five patients from three unrelated families with recessive missense and splice site COL25A1 variants presenting with a recognizable phenotype characterized by arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype. The clinical features of the older patients remained stable over time, without central nervous system involvement. This study extends the phenotypic and genotypic spectrum of COL25A1 related conditions, and further adds to our knowledge of the complex process of intramuscular motor innervation. Our observations indicate a role for collagen XXV in regulating the appropriate innervation not only of extraocular muscles, but also of bulbar, axial, and limb muscles in the human.},
	keywords = {Arthrogryposis, Face, Humans, Muscle, Skeletal, Mutation, Phenotype},
	issn = {1098-1004},
	doi = {10.1002/humu.24333},
	author = {Natera-de Benito, Daniel and Jurgens, Julie A and Yeung, Alison and Zaharieva, Irina T and Manzur, Adnan and DiTroia, Stephanie P and Di Gioia, Silvio Alessandro and Pais, Lynn and Pini, Veronica and Barry, Brenda J and Chan, Wai-Man and Elder, James E and Christodoulou, John and Hay, Eleanor and England, Eleina M and Munot, Pinki and Hunter, David G and Feng, Lucy and Ledoux, Danielle and O{\textquoteright}Donnell-Luria, Anne and Phadke, Rahul and Engle, Elizabeth C and Sarkozy, Anna and Muntoni, Francesco}
}
@article {1608576,
	title = {Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses},
	journal = {Cell},
	volume = {184},
	number = {17},
	year = {2021},
	month = {2021 08 19},
	pages = {4401-4413.e10},
	abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape convalescent and vaccine-induced antibody responses has renewed focus on the development of broadly protective T-cell-based vaccines. Here, we apply structure-based network analysis and assessments of HLA class I peptide stability to define mutationally constrained CD8+ T\&nbsp;cell epitopes across the SARS-CoV-2 proteome. Highly networked residues are conserved temporally among circulating variants and sarbecoviruses and disproportionately impair spike pseudotyped lentivirus infectivity when mutated. Evaluation of HLA class I stabilizing activity for 18 globally prevalent alleles identifies CD8+ T\&nbsp;cell epitopes within highly networked regions with limited mutational frequencies in circulating SARS-CoV-2 variants and deep-sequenced primary isolates. Moreover, these epitopes elicit demonstrable CD8+ T\&nbsp;cell reactivity in convalescent individuals but reduced recognition in recipients of mRNA-based vaccines. These data thereby elucidate key mutationally constrained regions and immunogenic epitopes in the SARS-CoV-2 proteome for a global T-cell-based vaccine against emerging variants and SARS-like coronaviruses.},
	keywords = {CD8-Positive T-Lymphocytes, COVID-19, COVID-19 Vaccines, Epitopes, T-Lymphocyte, HLA Antigens, Humans, SARS-CoV-2, Spike Glycoprotein, Coronavirus},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2021.06.029},
	author = {Nathan, Anusha and Rossin, Elizabeth J and Kaseke, Clarety and Park, Ryan J and Khatri, Ashok and Koundakjian, Dylan and Urbach, Jonathan M and Singh, Nishant K and Bashirova, Arman and Tano-Menka, Rhoda and Senjobe, Fernando and Waring, Michael T and Piechocka-Trocha, Alicja and Garcia-Beltran, Wilfredo F and Iafrate, A John and Naranbhai, Vivek and Carrington, Mary and Walker, Bruce D and Gaiha, Gaurav D}
}
@article {1586144,
	title = {Ultra-widefield autofluorescence imaging findings in retinoschisis, rhegmatogenous retinal detachment and combined retinoschisis retinal detachment},
	journal = {Acta Ophthalmol},
	volume = {99},
	number = {2},
	year = {2021},
	month = {2021 Mar},
	pages = {195-200},
	abstract = {PURPOSE: Retinoschisis (RS), rhegmatogenous retinal detachment (RRD) and combined RS retinal detachment (RSRD) may resemble clinically and pose a diagnostic challenge. This study investigates the role of the fundus autofluorescence (AF) in differentiating RS, RRD and RSRD. METHODS: Fundus AF changes of 34 eyes diagnosed with RRD, 30 eyes with RS and 12 eyes with RSRD were retrospectively analysed. Ultra-widefield AF (UW-AF) image intensities obtained with the Optomap 200Tx were interpreted as hypo-, hyper- and isoautofluorescent or a mixed pattern with hypo- and hyperautofluorescence over and at the posterior margin (PM) of RRD, RS and RSRD. RESULTS: All RS eyes revealed isoautofluorescence over the area of RS, and nine eyes (30\%) showed hypoautofluorescent PM. Among RRD, acute (<=2\&nbsp;weeks) and chronic (\&gt;2\&nbsp;weeks) RRD demonstrated distinct AF characteristics. Sixty-two per cent of RRD eyes had acute RRD. From those, 16 eyes (76\%) demonstrated hypoautofluorescence over the detached area and 19 (90\%) eyes with hyperautofluorescent PM. Sixty-two per cent of chronic RRD eyes demonstrated isoautofluorecence over the detached area. Eight RSRD eyes (67\%) revealed hyperautofluorescence in the detached area. The positive predictive value (PPV) for hypoautofluorescence over the area of subretinal fluid (SRF) in RRD was 95\%. The PPV for hyperautofluorescence over the area of SRF in RSRD was 100\% and for isoautofluorescence for schitic area in RSRD and RS was 76\%. CONCLUSION: The UW-AF can be a useful non-invasive adjuvant tool to distinguish between RRD, RS and RSRD. Hypo- or hyperautofluorescence over the area of interest and hyperautofluorescent PM indicates the presence of SRF.},
	issn = {1755-3768},
	doi = {10.1111/aos.14521},
	author = {Navaratnam, Jesintha and Salvanos, Panagiotis and Vavvas, Demetrios G and Bragad{\'o}ttir, Ragnhei{\dh}ur}
}
@article {341661,
	title = {Phy-Mer: a novel alignment-free and reference-independent mitochondrial haplogroup classifier.},
	journal = {Bioinformatics},
	volume = {31},
	number = {8},
	year = {2015},
	month = {2015 Apr 15},
	pages = {1310-2},
	abstract = {MOTIVATION: All current mitochondrial haplogroup classification tools require variants to be detected from an alignment with the reference sequence and to be properly named according to the canonical nomenclature standards for describing mitochondrial variants, before they can be compared with the haplogroup determining polymorphisms. With the emergence of high-throughput sequencing technologies and hence greater availability of mitochondrial genome sequences, there is a strong need for an automated haplogroup classification tool that is alignment-free and agnostic to reference sequence. RESULTS: We have developed a novel mitochondrial genome haplogroup-defining algorithm using a k-mer approach namely Phy-Mer. Phy-Mer performs equally well as the leading haplogroup classifier, HaploGrep, while avoiding the errors that may occur when preparing variants to required formats and notations. We have further expanded Phy-Mer functionality such that next-generation sequencing data can be used directly as input. AVAILABILITY AND IMPLEMENTATION: Phy-Mer is publicly available under the GNU Affero General Public License v3.0 on GitHub (https://github.com/danielnavarrogomez/phy-mer). CONTACT: Xiaowu_Gai@meei.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
	issn = {1367-4811},
	doi = {10.1093/bioinformatics/btu825},
	author = {Navarro-Gomez, Daniel and Leipzig, Jeremy and Shen, Lishuang and Lott, Marie and Stassen, Alphons P M and Wallace, Douglas C and Wiggs, Janey L and Falk, Marni J and van Oven, Mannis and Gai, Xiaowu}
}
@article {1603868,
	title = {Lymphoma of the Lacrimal Sac: The Massachusetts Eye and Ear Experience With a Comparison to the Previously Reported Literature},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {1},
	year = {2022},
	month = {2022 Jan-Feb 01},
	pages = {79-86},
	abstract = {PURPOSE: To describe the frequency, clinical features, and histologic subtypes of biopsy proven lacrimal sac lymphomas, and to compare these results to the previously published literature. METHODS: A retrospective chart review was performed at a single institution from 2004 to 2017. Pathology reports, operative notes, and patients{\textquoteright} medical charts were reviewed. RESULTS: Of 566 lacrimal sacs submitted for routine histopathologic evaluation, 16 cases of lymphoma were identified. All were low-grade, non-Hodgkin B-cell lymphomas, biopsied at an average age of 71 years. Thirteen patients (81.25\%) had a pre-existing lymphoma diagnosis; the average interval between the diagnosis of systemic or nonocular adnexal lymphoma and lacrimal sac lymphoma was 7.9 years (range 2-26 years; median 5.5 years). Three cases of primary lacrimal sac lymphoma were identified. Histopathology showed 3 cases (18.75\%) of follicular lymphoma, 3 (18.75\%) of extranodal marginal zone lymphoma, and 10 (62.5\%) of chronic lymphocytic leukemia/small lymphocytic lymphoma. Primary cases presented with epiphora and nasolacrimal duct obstruction, while secondary cases predominantly manifested as dacryocystitis. All lacrimal sac neoplasms were locally responsive (without local recurrence) to chemotherapy, radiation, or both. CONCLUSIONS: Lacrimal sac lymphoma is uncommon but should be suspected among patients with known lymphoma who develop dacryocystitis. In this series, primary lacrimal sac lymphoma most often presented as a mass or nasolacrimal duct obstruction. Chronic lymphocytic leukemia/small lymphocytic lymphoma was the most commonly identified cause of secondary lacrimal sac lymphoma. Distinguishing primary from secondary lacrimal sac lymphomas is important, as the extent of disease and histopathologic subtypes differ, which may affect patient management.},
	keywords = {Aged, Dacryocystitis, Dacryocystorhinostomy, Humans, Lacrimal Apparatus Diseases, Lacrimal Duct Obstruction, Lymphoma, B-Cell, Marginal Zone, Nasolacrimal Duct, Retrospective Studies},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001997},
	author = {Neerukonda, Vamsee K and Stagner, Anna M and Wolkow, Natalie}
}
@article {1559548,
	title = {Lacrimal Gland Intravascular Micrometastasis From a Human Papillomavirus-Driven Anorectal Squamous Cell Carcinoma With a Review of Metastatic Disease to the Lacrimal Gland},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2020},
	month = {2020 Dec 07},
	abstract = {PURPOSE: To document a unique case of anorectal squamous cell carcinoma that was metastatic to the microvasculature of the lacrimal gland in a patient with human immunodeficiency virus and to review previously reported cases of metastases to the lacrimal gland. METHODS: Both a retrospective chart review and comprehensive literature review were performed. The unusual histopathologic pattern of the current case was illustrated with immunohistochemical studies (CD31, D2-40, pancytokeratin, p16, and p63) and in situ hybridization studies for high-risk human papillomavirus types 16 and 18. RESULTS: The authors describe the first case of metastatic anorectal squamous cell carcinoma to the lacrimal gland. Only 24 cases of metastatic disease to the lacrimal gland have been reported, the majority from breast carcinomas. The metastasis did not form a macroscopic lesions, instead was composed of microscopic intravascular and intraparenchymal tumor deposits, a subtle phenomena. Immunohistochemistry confirmed the presence of the intravascular neoplastic cells. p16 served as a surrogate marker for human papillomavirus-associated squamous cell carcinoma and was confirmed with in situ hybridization for human papillomavirus 16 and 18. This testing, combined with the clinical history, defined the diagnosis and confirmed human papillomavirus as the tumor driver. CONCLUSIONS: Metastases to the lacrimal gland remain rare, but clinicians and pathologists alike must be attuned to the possibility of subtle microscopic foci of tumor as a pattern of metastasis in scenarios without a discrete mass-forming lesion, as this may portend a poor prognosis.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001894},
	author = {Neerukonda, Vamsee K and Jakobiec, Frederick A and Freitag, Suzanne K and Stagner, Anna M and Wolkow, Natalie}
}
@article {1653605,
	title = {Silicone Granulomas of the Eyelids-A Case Series Illustrating a Distant Migratory Phenomenon},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {1},
	year = {2023},
	month = {2023 Jan-Feb 01},
	pages = {81-87},
	abstract = {PURPOSE: Exogenous silicone has been reported to migrate to anatomic sights far from an initial injection or implantation site; this phenomenon has been rarely described in the ocular adnexa, especially in the eyelids. We document 3 additional cases of distant migration of silicone implanted elsewhere in the body to the eyelids and review the prior literature on this uncommon event. METHODS: A retrospective chart review of 3 patients was conducted along with analysis of diagnostic histopathology. A comprehensive review of the literature regarding dissemination or migration of silicone to the eyelids in patients with either silicone breast implants or silicone facial filler use was performed. RESULTS: Cases of silicone migrating to the eyelids from silicone breast implants and silicone-based facial filler are outlined in Tables 1 and 2, respectively. There are 4 total reports of women with silicone breast implants, including the 2 described here, with evidence of migration of silicone to the eyelid. Similarly, 5 cases of silicone-based facial filler with resultant migration of filler to the eyelids were identified, including 2 of the cases presented in this report (1 patient had both silicone breast implants and silicone facial filler). CONCLUSION: Silicone is chemically inert, but is known to travel throughout the body, causing a resultant foreign body response in tissue that can adversely affect even the eyelids. Silicone has a relatively characteristic histologic appearance and diagnosis of silicone granuloma highlights the importance of obtaining a thorough clinical history, particularly regarding prior cosmetic injections or breast enhancement surgery. Foreign material/foreign body granuloma is important to consider in patients with deep eyelid nodules of unclear etiology.},
	keywords = {Eyelids, Female, Granuloma, Foreign-Body, Humans, Prostheses and Implants, Retrospective Studies, Silicones},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002255},
	author = {Neerukonda, Vamsee K and Lefebvre, Daniel and Chatson, George P and Stagner, Anna M}
}
@article {1806666,
	title = {Histopathologic alterations in the eyelid after Hughes tarsoconjunctival flap: loss of Meibomian glands with preservation of accessory lacrimal glands},
	journal = {Orbit},
	volume = {43},
	number = {1},
	year = {2024},
	month = {2024 Feb},
	pages = {115-118},
	abstract = {A 71-year-old female with invasive squamous cell carcinoma of the lower eyelid involving the ocular surface underwent surgical excision with negative margins and a subsequent reconstruction. The posterior lamellar defect was reconstructed with a Hughes tarsoconjunctival flap, and the anterior lamellar defect was reconstructed by advancing the lower eyelid skin. Three years later, the patient presented with signs suspicious for recurrence involving the tarsoconjunctival graft: a nodule along the mucocutaneus junction, symblepharon, and forniceal shortening. Repeat scouting biopsies showed variable degrees of moderate to severe squamous dysplasia so the patient underwent a staged full thickness excision of the lower eyelid and involved conjunctiva followed by reconstruction. Direct immunofluorescence was not diagnostic for ocular cicatrcial pemphigoid. Permanent histopathologic sections did not show any carcinoma, but the full thickness excisions involving the prior Hughes tarsoconjunctival flap highlighted two notable alterations: the Meibomian glands were absent and the accessory lacrimal glands of Wolfring were transposed to the mucocutaneous junction of the reconstructed lower eyelid.},
	keywords = {Aged, Blepharoplasty, Conjunctiva, Eyelid Diseases, Eyelid Neoplasms, Female, Humans, Lacrimal Apparatus, Meibomian Glands, Surgical Flaps},
	issn = {1744-5108},
	doi = {10.1080/01676830.2022.2080232},
	author = {Neerukonda, Vamsee K and Freitag, Suzanne K and Wolkow, Natalie}
}
@article {1603847,
	title = {Florid sympathetic ophthalmia},
	journal = {Orbit},
	year = {2021},
	month = {2021 Jul 05},
	pages = {1},
	issn = {1744-5108},
	doi = {10.1080/01676830.2021.1939733},
	author = {Neerukonda, Vamsee K and Stagner, Anna M and Wolkow, Natalie}
}
@article {1635643,
	title = {Primary vitreoretinal involvement and immunopositivity for BRAFV600E help distinguish metastatic from primary intraocular melanoma: a detailed histopathologic study of metastatic cutaneous melanoma to the eye},
	journal = {Histopathology},
	volume = {80},
	number = {7},
	year = {2022},
	month = {2022 Jun},
	pages = {1061-1070},
	abstract = {OBJECTIVE: To evaluate the clinicopathologic characteristics of metastatic cutaneous melanoma to the eye and identify potential distinguishing characteristics from the more common primary uveal melanoma; particularly, tumour location within the eye, cytomorphology and immunohistochemical/specific molecular genetic features. METHODS: A retrospective observational case series using surgical enucleation and diagnostic vitrectomy cytologic specimens from seven patients with suspected intraocular melanoma, eventually diagnosed as metastatic melanoma, was conducted. Haematoxylin and eosin-stained sections of tumour and immunohistochemical (IHC) stains for BRAFV600E and Ki-67 were critically reviewed; BAP1 IHC was also evaluated in cases where additional tissue was available. Clinical imaging studies and medical records were reviewed. RESULTS: The majority of patients (86\%) with metastatic melanoma have primary vitreoretinal (not uveal) involvement and epithelioid, highly malignant cytomorphology (100\%); many (50\%) harbour BRAFV600E mutations, a finding not seen in large cohorts of primary uveal melanoma. CONCLUSIONS: Characteristics favouring or defining metastatic intraocular melanoma over primary uveal melanoma include high-grade epithelioid cytology, predominant involvement of the vitreous cavity and/or retina, and presence of positive immunostaining for BRAFV600E.},
	keywords = {Diagnosis, Differential, Eye Neoplasms, Humans, Melanoma, Proto-Oncogene Proteins B-raf, Retrospective Studies, Skin Neoplasms, Uveal Neoplasms},
	issn = {1365-2559},
	doi = {10.1111/his.14640},
	author = {Neerukonda, Vamsee K and Kim, Ivana K and Stagner, Anna M}
}
@article {1615218,
	title = {Effect of a Randomized Interventional School-Based Vision Program on Academic Performance of Students in Grades 3 to 7: A Cluster Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {10},
	year = {2021},
	month = {2021 Oct 01},
	pages = {1104-1114},
	abstract = {Importance: Uncorrected refractive error in school-aged children may affect learning. Objective: To assess the effect of a school-based vision program on academic achievement among students in grades 3 to 7. Design, Setting, and Participants: This cluster randomized clinical trial was conducted in Baltimore City Public Schools during school years from 2016 to 2019 among 2304 students in grades 3 to 7 who received eye examinations and eyeglasses. Intervention: Participating schools were randomized 1:1:1 to receive eye examinations and eyeglasses during 1 of 3 school years (2016-2017, 2017-2018, and 2018-2019). Main Outcomes and Measures: The primary outcome was 1-year intervention impact, measured by effect size (ES), defined as the difference in score on an academic test (i-Ready or Partnership for Assessment of Readiness for College and Careers tests on reading and mathematics) between intervention and control groups measured in SD units, comparing cohort 1 (intervention) with cohorts 2 and 3 (control) at the end of program year 1 and comparing cohort 2 (intervention) with cohort 3 (control) at the end of program year 2. The secondary outcome was 2-year intervention impact, comparing ES in cohort 1 (intervention) with cohort 3 (control) at the end of program year 2. Hierarchical linear modeling was used to assess the impact of the intervention. Analysis was performed on an intention-to-treat basis. Results: Among the 2304 students included in the study, 1260 (54.7\%) were girls, with a mean (SD) age of 9.4 (1.4) years. The analysis included 964 students (41 schools) in cohort 1, 775 students (41 schools) in cohort 2, and 565 students (38 schools) in cohort 3. There were 1789 Black students (77.6\%), 388 Latinx students (16.8\%), and 406 students in special education (17.6\%). There was an overall 1-year positive impact (ES, 0.09; P = .02) as assessed by the i-Ready reading test during school year 2016-2017. Positive impact was also observed among female students (ES, 0.15; P \&lt; .001), those in special education (ES, 0.25; P \&lt; .001), and students who performed in the lowest quartile at baseline (ES, 0.28; P \&lt; .001) on i-Ready reading and among students in elementary grades on i-Ready mathematics (ES, 0.03; P \&lt; .001) during school year 2016-2017. The intervention did not show a sustained impact at 2 years or on Partnership for Assessment of Readiness for College and Careers testing. Conclusions and Relevance: Students in grades 3 to 7 who received eyeglasses through a school-based vision program achieved better reading scores. Students had improved academic achievement over 1 year; however, a sustained impact was not observed after 2 years. Trial Registration: The Registry of Efficacy and Effectiveness Studies Identifier: 1573.1v1.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.3544},
	author = {Neitzel, Amanda J and Wolf, Betsy and Guo, Xinxing and Shakarchi, Ahmed F and Madden, Nancy A and Repka, Michael X and Friedman, David S and Collins, Megan E}
}
@article {1125361,
	title = {TFOS DEWS II Introduction},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {269-275},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.05.005},
	author = {Nelson, J Daniel and Craig, Jennifer P and Akpek, Esen K and Azar, Dimitri T and Belmonte, Carlos and Bron, Anthony J and Clayton, Janine A and Dogru, Murat and Dua, Harminder S and Foulks, Gary N and Gomes, Jos{\'e} A P and Hammitt, Katherine M and Holopainen, Juha and Jones, Lyndon and Joo, Choun-Ki and Liu, Zuguo and Nichols, Jason J and Nichols, Kelly K and Novack, Gary D and Sangwan, Virender and Stapleton, Fiona and Tomlinson, Alan and Tsubota, Kazuo and Willcox, Mark D P and Wolffsohn, James S and Sullivan, David A}
}
@article {1782401,
	title = {The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegeneration and neuroinflammation},
	journal = {Nat Neurosci},
	volume = {26},
	number = {12},
	year = {2023},
	month = {2023 Dec},
	pages = {2104-2121},
	abstract = {Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer{\textquoteright}s disease (LOAD), leading to earlier age of clinical onset and exacerbating pathologies. There is a critical need to identify protective targets. Recently, a rare APOE variant, APOE3-R136S (Christchurch), was found to protect against early-onset AD in a PSEN1-E280A carrier. In this study, we sought to determine if the R136S mutation also protects against APOE4-driven effects in LOAD. We generated tauopathy mouse and human iPSC-derived neuron models carrying human APOE4 with the homozygous or heterozygous R136S mutation. We found that the homozygous R136S mutation rescued APOE4-driven Tau pathology, neurodegeneration and neuroinflammation. The heterozygous R136S mutation partially protected against APOE4-driven neurodegeneration and neuroinflammation but not Tau pathology. Single-nucleus RNA sequencing revealed that the APOE4-R136S mutation increased disease-protective and diminished disease-associated cell populations in a gene dose-dependent manner. Thus, the APOE-R136S mutation protects against APOE4-driven AD pathologies, providing a target for therapeutic development against AD.},
	keywords = {Alzheimer Disease, Animals, Apolipoprotein E3, Apolipoprotein E4, Humans, Mice, Mutation, Neuroinflammatory Diseases, Tauopathies},
	issn = {1546-1726},
	doi = {10.1038/s41593-023-01480-8},
	author = {Nelson, Maxine R and Liu, Peng and Agrawal, Ayushi and Yip, Oscar and Blumenfeld, Jessica and Traglia, Michela and Kim, Min Joo and Koutsodendris, Nicole and Rao, Antara and Grone, Brian and Hao, Yanxia and Yoon, Seo Yeon and Xu, Qin and De Leon, Samuel and Choenyi, Tenzing and Thomas, Reuben and Lopera, Francisco and Quiroz, Yakeel T and Arboleda-Velasquez, Joseph F and Reiman, Eric M and Mahley, Robert W and Huang, Yadong}
}
@article {1761856,
	title = {Patient Experience with Virtual Preoperative Consultations in Pediatric Surgical Specialties},
	journal = {J Pediatr Surg},
	volume = {58},
	number = {9},
	year = {2023},
	month = {2023 Sep},
	pages = {1776-1782},
	abstract = {BACKGROUND: A cross-sectional study was conducted to assess the comparative effectiveness of virtual visits for preoperative evaluation and surgical decision-making in three pediatric surgical subspecialties. METHODS: Patients who underwent surgical procedures in the departments of Urology, Ophthalmology, and Plastic and Oral Surgery at a tertiary care pediatric hospital over a one-year period during the COVID-19 pandemic were included. Patients were assigned to one of three clinical pathways based on their preoperative visit(s): only in-person visit(s) (IP), a combination of in-person and virtual visit(s) (IP/VV), and only virtual visit(s) (VV). Demographics, procedure information, and patient experience survey results were collected. We then assessed variations in procedure types and patient experience scores in these three patient groups. RESULTS: There were 431 patients who completed the modified patient experience survey. The most common procedures were circumcision (17\%), excision of lesion (16\%), and strabismus repair (11\%). Survey results were positive, with 90\% of participants rating that they would recommend the service to others. No significant differences were found among groups in their demographics, overall care rating, and duration between preoperative clinic visit and procedure. Post-hoc power analysis indicated 87\% power to detect a 10\% difference in survey ratings between IP and VV cases, confirming non-inferiority in patient satisfaction for virtual preoperative visits. CONCLUSION: This study demonstrated the non-inferiority of preoperative virtual visits in three pediatric surgical subspecialties as measured by patient experience scores. Additional studies with more granular scope are necessary to further elucidate telemedicine{\textquoteright}s safety and efficacy for select diagnoses. LEVEL OF EVIDENCE: III.},
	keywords = {Child, COVID-19, Cross-Sectional Studies, Humans, Male, Pandemics, Patient Outcome Assessment, Patient Satisfaction, Referral and Consultation, Telemedicine, Urology},
	issn = {1531-5037},
	doi = {10.1016/j.jpedsurg.2022.12.027},
	author = {Netson, Rebecca A and Miller, Stephanie and Incorvia, Joseph and Shah, Ankoor and Estrada, Carlos R and Toomey, Sara L and Taghinia, Amir H}
}
@article {591196,
	title = {Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.},
	journal = {JAMA},
	volume = {314},
	number = {20},
	year = {2015},
	month = {2015 Nov 24},
	pages = {2137-46},
	abstract = {IMPORTANCE: Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE: To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44\% female; 52\% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS: Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES: The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS: Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95\% CI, -0.5 to +5.0; P \&lt; .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95\% CI, +3.0 to +5.4; P \&lt; .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95\% CI, 213-531 dB; P \&lt; .001), vitrectomy was more frequent (15\% vs 4\%; difference, 9\%; 95\% CI, 4\%-15\%; P \&lt; .001), and DME development was more frequent (28\% vs 9\%; difference, 19\%; 95\% CI, 10\%-28\%; P \&lt; .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35\% in the ranibizumab group vs 30\% in the PRP group; difference, 3\%; 95\% CI, -7\% to 12\%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE: Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01489189.},
	issn = {1538-3598},
	doi = {10.1001/jama.2015.15217},
	author = {Writing Committee for the Diabetic Retinopathy Clinical Research Network and Gross, Jeffrey G and Glassman, Adam R and Jampol, Lee M and Inusah, Seidu and Aiello, Lloyd Paul and Antoszyk, Andrew N and Baker, Carl W and Berger, Brian B and Bressler, Neil M and Browning, David and Elman, Michael J and Ferris, Frederick L and Friedman, Scott M and Marcus, Dennis M and Melia, Michele and Stockdale, Cynthia R and Sun, Jennifer K and Beck, Roy W}
}
@article {1470983,
	title = {ISOPT Hot Topic Panel Discussion on Uveitis and Inflammation},
	journal = {J Ocul Pharmacol Ther},
	volume = {35},
	number = {8},
	year = {2019},
	month = {2019 Oct},
	pages = {433-440},
	abstract = {For this "hot topic" session in uveitis we selected first and foremost an issue that puts our clinical work and research in "holding pattern." The issue is our method of evaluating the severity of uveitis. We posed the following questions to our esteemed panelists: 1.The relative significance of cells vs. flare in following uveitis patients 2.Cells/flare measurements 3.A glance into the future and the relevance of endpoints in clinical studies and their methodologies While there are different opinions in managing and monitoring uveitis patients, there seems to be an agreement on the high need of improving objective mode/s of reliably measuring both cells and flare and better understand their significance.},
	issn = {1557-7732},
	doi = {10.1089/jop.2019.0035},
	author = {Neumann, Ron and Nguyen, Quan Dong and Kramer, Michal and Zierhut, Manfred and Kempen, John H and DeSmet, Marc and Wickstrom, Kerstin}
}
@article {1658667,
	title = {Randomized trial of bilateral gene therapy injection for m.11778G\&gt;A MT-ND4 Leber optic neuropathy},
	journal = {Brain},
	volume = {146},
	number = {4},
	year = {2023},
	month = {2023 Apr 19},
	pages = {1328-1341},
	abstract = {Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G\&gt;A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G\&gt;A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P \&lt; 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P \&lt; 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4\% and 72.0\% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7\% of lenadogene nolparvovec-treated eyes versus 10.2\% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G\&gt;A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.},
	keywords = {DNA, Mitochondrial, Genetic Therapy, Humans, Inflammation, Mutation, Optic Atrophy, Hereditary, Leber},
	issn = {1460-2156},
	doi = {10.1093/brain/awac421},
	author = {Newman, Nancy J and Yu-Wai-Man, Patrick and Subramanian, Prem S and Moster, Mark L and Wang, An-Guor and Donahue, Sean P and Leroy, Bart P and Carelli, Valerio and Biousse, Valerie and Vignal-Clermont, Catherine and Sergott, Robert C and Sadun, Alfredo A and Fern{\'a}ndez, Gema Rebolleda and Chwalisz, Bart K and Banik, Rudrani and Bazin, Fabienne and Roux, Michel and Cox, Eric D and Taiel, Magali and Sahel, Jos{\'e}-Alain and LHON REFLECT Study Group}
}
@article {1351174,
	title = {The potential association between postmenopausal hormone use and primary open-angle glaucoma},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {3},
	year = {2014},
	month = {2014 Mar},
	pages = {298-303},
	abstract = {IMPORTANCE: Retinal ganglion cells are known to express estrogen receptors and prior studies have suggested an association between postmenopausal hormone (PMH) use and decreased intraocular pressure, suggesting that PMH use may decrease the risk for primary open-angle glaucoma (POAG). OBJECTIVE: To determine whether the use of 3 different classes of PMH affects the risk for POAG. DESIGN, SETTING, AND PARTICIPANTS: Retrospective longitudinal cohort analysis of claims data from women 50 years or older enrolled in a US managed-care plan for at least 4 years in which enrollees had at least 2 visits to an eye care provider during the period 2001 through 2009. EXPOSURE: Postmenopausal hormone medications containing estrogen only, estrogen + progesterone, and estrogen + androgen, as captured from outpatient pharmacy claims over a 4-year period. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for developing incident POAG. RESULTS: Of 152,163 eligible enrollees, 2925 (1.9\%) developed POAG. After adjustment for confounding factors, each additional month of use of PMH containing estrogen only was associated with a 0.4\% reduced risk for POAG (HR, 0.996 [95\% CI, 0.993-0.999]; P = .02). The risk for POAG did not differ with each additional month of use of estrogen + progesterone (HR, 0.994 [95\% CI, 0.987-1.001]; P = .08) or estrogen + androgen (HR, 0.999 [95\% CI, 0.988-1.011]; P = .89). CONCLUSIONS AND RELEVANCE: Use of PMH preparations containing estrogen may help reduce the risk for POAG. If prospective studies confirm the findings of this analysis, novel treatments for this sight-threatening condition may follow.},
	keywords = {Aged, Androgens, Drug Combinations, Drug Prescriptions, Estrogen Replacement Therapy, Estrogens, Female, Glaucoma, Open-Angle, Humans, Incidence, Intraocular Pressure, Managed Care Programs, Middle Aged, Progesterone, Proportional Hazards Models, Retrospective Studies, Risk Factors, Tonometry, Ocular, United States},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.7618},
	author = {Newman-Casey, Paula Anne and Talwar, Nidhi and Nan, Bin and Musch, David C and Pasquale, Louis R and Stein, Joshua D}
}
@article {1677706,
	title = {The role of a multicentre data repository in ocular inflammation: The Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS)},
	journal = {Eye (Lond)},
	volume = {37},
	number = {15},
	year = {2023},
	month = {2023 Oct},
	pages = {3084-3096},
	abstract = {In the current literature, clinical registry cohorts related to ocular inflammation are few and far between, and there are none involving multi-continental international data. Many existing registries comprise administrative databases, data related to specific uveitic diseases, or are designed to address a particular clinical problem. The existing data, although useful and serving their intended purposes, are segmented and may not be sufficiently robust to design prognostication tools or draw epidemiological conclusions in the field of uveitis and ocular inflammation. To solve this, we have developed the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) Clinical Registry. OASIS collects prospective and retrospective data on patients with all types of ocular inflammatory conditions from centers all around the world. It is a primarily web-based platform with alternative offline modes of access. A comprehensive set of clinical data ranging from demographics, past medical history, clinical presentation, working diagnosis to visual outcomes are collected over a range of time points. Additionally, clinical images such as optical coherence tomography, fundus fluorescein angiography and indocyanine green angiography studies may be uploaded. Through the capturing of diverse, well-structured, and clinically meaningful data in a simplified and consistent fashion, OASIS will deliver a comprehensive and well organized data set ripe for data analysis. The applications of the registry are numerous, and include performing epidemiological analysis, monitoring drug side effects, and studying treatment safety efficacy. Furthermore, the data compiled in OASIS will be used to develop new classification and diagnostic systems, as well as treatment and prognostication guidelines for uveitis.},
	keywords = {Fluorescein Angiography, Humans, Inflammation, Multicenter Studies as Topic, Prospective Studies, Retrospective Studies, Tomography, Optical Coherence, Uveitis},
	issn = {1476-5454},
	doi = {10.1038/s41433-023-02472-5},
	author = {Ng, Sean Ming Sheng and Low, Rebecca and Pak, Clara and Lai, SerSei and Lee, Bernett and McCluskey, Peter and Symes, Richard and Invernizzi, Alessandro and Tsui, Edmund and Sitaula, Ranju Kharel and Kharel, Muna and Khatri, Anadi and Utami, Anna Nur and Distia Nora, Rina La and Putera, Ikhwanuliman and Sen, Alok and Agarwal, Manisha and Mahendradas, Padmamalini and Biswas, Jyotirmay and Pavesio, Carlos and Cimino, Luca and Sobrin, Lucia and Kempen, John H and Gupta, Vishali and Agrawal, Rupesh and OASIS Study Group}
}
@article {1593849,
	title = {CATASTROPHIC, BILATERAL RETINAL VASCULAR OCCLUSION AFTER INTRAVITREAL BEVACIZUMAB INJECTION},
	journal = {Retin Cases Brief Rep},
	volume = {17},
	number = {2},
	year = {2023},
	month = {2023 Mar 01},
	pages = {81-84},
	abstract = {PURPOSE: To describe two cases of catastrophic, bilateral retinal vascular occlusion after intravitreal (IVT) bevacizumab injection. METHODS: Case series. Main outcome measures included clinical and fluorescein angiography findings. RESULTS: Case 1-A 65-year-old woman with calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis syndrome developed acute, severe, bilateral visual loss 2 weeks after bilateral IVT bevacizumab injection for proliferative diabetic retinopathy. Examination and fluorescein angiography revealed moderate anterior chamber inflammation, bilateral perivascular retinal hemorrhages, and near total retinal vascular occlusion. Extensive testing revealed moderately elevated anti-B2 glycoprotein (antiphospholipid) antibodies. Case 2-An 85-year-old man with polymyalgia rheumatica and left eye exudative age-related macular degeneration experienced severe, bilateral, sequential visual loss in the left eye and then right eye approximately 3 weeks after IVT bevacizumab left eye injection. Examination revealed bilateral panuveitis, diffuse perivascular exudates, and intraretinal hemorrhages. Fluorescein angiography showed diffuse venous leakage. Extensive testing revealed an elevated antinuclear antibody and mildly elevated anticardiolipin antibody. CONCLUSION: Patients with underlying retinal vascular vulnerabilities may be at increased risk of catastrophic, bilateral retinal vascular occlusion after treatment with IVT bevacizumab. The moderate-to-severe intraocular inflammation in both cases and the contralateral involvement after unilateral IVT injection in Case 2 suggest a possible delayed immune-mediated mechanism.},
	keywords = {Aged, Aged, 80 and over, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Bevacizumab, Female, Fluorescein Angiography, Humans, Infant, Newborn, Inflammation, Intravitreal Injections, Male, Retinal Diseases, Vascular Endothelial Growth Factor A},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001158},
	author = {Ng, Caleb C and Brill, Daniel and Cunningham, Emmett T and Burckhard, Braden A and Jumper, J Michael and Heier, Jeffrey and Rifkin, Lana M and Eliott, Dean and McDonald, H Richard and Sobrin, Lucia}
}
@article {1655705,
	title = {Outcome of Cataract Surgery in Patients With Retinitis Pigmentosa},
	journal = {Am J Ophthalmol},
	volume = {246},
	year = {2023},
	month = {2023 Feb},
	pages = {1-9},
	abstract = {PURPOSE: To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP). DESIGN: Retrospective, noncomparative clinical study. METHODS: Preoperative, intraoperative, and postoperative data of patients with RP who were undergoing cataract surgery were collected from several expertise centers across Europe. RESULTS: In total, 295 eyes of 226 patients were included in the study. The mean age at surgery of the first eye was 56.1 {\textpm} 17.9 years. Following surgery, best-corrected visual acuity (BCVA) improved significantly from 1.03 to 0.81 logMAR (ie, 20/214 to 20/129 Snellen) in the first treated eye (-0.22 logMAR; 95\% CI\&nbsp;=\&nbsp;-0.31 to -0.13; P \&lt; .001) and from 0.80 to 0.56 logMAR (ie, 20/126 to 20/73 Snellen) in the second treated eye (-0.24 logMAR; 95\% CI\&nbsp;=\&nbsp;-0.32 to -0.15; P \&lt; .001). Marked BCVA improvements (postoperative change in BCVA of >=0.3 logMAR) were observed in 87 of 226 patients (39\%). Greater odds for marked visual improvements were observed in patients with moderate visual impairment or worse. The most common complications were zonular dialysis (n\&nbsp;=\&nbsp;15; 5\%) and (exacerbation of) cystoid macular edema (n\&nbsp;=\&nbsp;14; 5\%), respectively. Postoperative posterior capsular opacifications were present in 111 of 295 eyes (38\%). CONCLUSION: Significant improvements in BCVA are observed in most patients with RP following cataract surgery. Baseline BCVA is a predictor of visual outcome. Preoperative evaluation should include the assessment of potential zonular insufficiency and the presence of CME, as they are relatively common and may increase the risk of complications.},
	keywords = {Adult, Aged, Capsule Opacification, Cataract, Humans, Lens Implantation, Intraocular, Middle Aged, Phacoemulsification, Retinitis Pigmentosa, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.10.001},
	author = {Nguyen, Xuan-Thanh-An and Thiadens, Alberta A H J and Fiocco, Marta and Tan, Weijen and McKibbin, Martin and Klaver, Caroline C W and Meester-Smoor, Magda A and Van Cauwenbergh, Caroline and Strubbe, Ine and Vergaro, Andrea and Pott, Jan-Willem R and Hoyng, Carel B and Leroy, Bart P and Zemaitiene, Reda and Khan, Kamron N and Boon, Camiel J F}
}
@article {1351175,
	title = {Stereotactic microdebrider in deep lateral orbital decompression for patients with thyroid eye disease},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {30},
	number = {3},
	year = {2014},
	month = {2014 May-Jun},
	pages = {262-6},
	abstract = {PURPOSE: Stereotactic navigation systems have been used in neurosurgery and otolaryngology with great success. The current investigation illustrates the novel use of a microdebrider with built-in stereotactic guidance in a series of thyroid orbitopathy patients who underwent deep lateral orbital wall decompression surgery. METHODS: A noncomparative, interventional, retrospective case series of patients who underwent deep lateral deep orbital wall decompression from 2006 to 2013 was conducted in accordance with Institutional Review Board policy and the Declaration of Helsinki. Patient demographics, indications for surgery, pre-, intra-, and postoperative findings along with complications were recorded. RESULTS: One hundred eight deep lateral orbital decompression surgeries were performed in 69 patients using the Straightshot M4 Microdebrider with built-in stereotactic guidance (Medtronics). Seventy-eight cases were in women and 30 cases were in men. The average age was 50.4 years (SD = 11.9 years). Indications for surgery included proptosis, exposure keratopathy, or compressive optic neuropathy. No patient experienced intraoperative complications. Specifically, cerebrospinal fluid leak, visual loss, infection, or unanticipated inflammation were not encountered. The average postoperative follow-up time was 5.35 months. Mean reduction in proptosis was 3.72 mm (SD = 2.1). Visual acuity improved in 32.4\% (35/108) of cases. CONCLUSIONS: This surgical instrument combines a single handpiece locator, microdebrider, irrigator, retractor, and suction device into one. It enhances anatomical localization during orbital decompression and, with an integrated tissue guard, may decrease the risk of injury to orbital soft tissues. Stereotactic navigation enhances the surgeon{\textquoteright}s ability to determine the maximal limits of decompression in real time by confirming depth of bone removal and may potentially increase surgeons{\textquoteright} confidence in orbital decompression surgery.},
	keywords = {Adult, Aged, Debridement, Decompression, Surgical, Exophthalmos, Eyelid Diseases, Female, Follow-Up Studies, Graves Ophthalmopathy, Humans, Male, Middle Aged, Nerve Compression Syndromes, Orbit, Retrospective Studies, Tomography, X-Ray Computed, Visual Acuity, Young Adult},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000132},
	author = {Nguyen, John and Fay, Aaron and Yadav, Prashant and MacIntosh, Peter W and Metson, Ralph}
}
@article {1598036,
	title = {Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {2},
	year = {2021},
	month = {2021 Jun 01},
	pages = {217-223},
	abstract = {BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83\% reported positional headache, 33\% reported transient visual obscurations, and 16\% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000926},
	author = {Nguyen, Huy V and Gilbert, Aubrey L and Fortin, Elizabeth and Vodopivec, Ivana and Torun, Nurhan and Chwalisz, Bart K and Cestari, Dean M and Rizzo, Joseph F}
}
@article {1213841,
	title = {Bilateral Upper and Lower Eyelid Margin Swelling and Madarosis due to Lymphoma},
	journal = {Surv Ophthalmol},
	year = {2017},
	month = {2017 Oct 03},
	abstract = {Over a 2 year period a 32-year-old woman developed swellings of all 4 eyelid margins accompanied by complete loss of eyelashes. An inflammatory dermatologic condition was considered the most likely cause. A full thickness right lower eyelid biopsy revealed a multinodular lymphoid tumor at the eyelid margin which immunophenotypically and genetically was diagnosed as an extranodal marginal zone lymphoma. The mode of presentation of the disease was considered to be most unusual, as was its B cell lineage, since the majority of primary cutaneous lymphomas are of T-cell origin. Systemic workup demonstrated bilateral involvement of the external auditory canals.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2017.09.007},
	author = {Nguyen, Huy V and Jakobiec, Frederick A and Zakka, Fouad R and Yoon, Michael K}
}
@article {1445325,
	title = {Impact of obstructive sleep apnea on optic nerve function in patients with craniosynostosis and recurrent intracranial hypertension},
	journal = {Am J Ophthalmol},
	year = {2019},
	month = {2019 Jun 19},
	abstract = {PURPOSE: Assessment of combined impact of intracranial pressure (ICH) and obstructive sleep apnea (OSA) on optic nerve function in children with craniosynostosis (CS). DESIGN: Retrospective cross-sectional study METHODS: Patients treated at Boston Children{\textquoteright}s Hospital for CS who had an ophthalmic examination that included pattern reversal (pr)VEP (2013-2014) and history of ICH based on direct measurement, papilledema, or classic features on neuroimaging and during cranial vault expansion were included. History of OSA was determined by polysomnography and associated conditions, including apnea and (adeno)tonsillectomy. Subjects were divided into four groups: (1) resolved ICH absent history of OSA; (2) resolved ICH with history of OSA; (3) recurrent ICH absent history of OSA; and (4) recurrent ICH with history of OSA. Predictor variables included latency of P100 component of prVEP, best-corrected visual acuity, optic nerve appearance, visual fields and global RNFL. Primary outcome was association of prolonged P100 latency with resolved versus recurrent ICH and OSA. RESULTS: Twenty-eight children met inclusion criteria (mean age 11.6 {\textpm} 6.9 years): group 1 (N = 3); group 2 (N = 6); group 3 (N = 8); group 4 (N = 11). P100 latencies were not prolonged in groups 1 and 2. Three of 8 in group 3 and 9 of 11 in group 4 had prolonged P100 latency. Group 4 was significantly worse than group 3 (P=0.005). CONCLUSIONS: History of OSA, in addition to recurrent ICH, is associated with greatest risk of optic neuropathy with CS. Ophthalmologists should encourage early management of OSA as well as ICH to optimize ophthalmic outcomes.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.06.011},
	author = {Nguyen, Josephine Q N and Resnick, Cory M and Chang, Yoon-Hee and Hansen, Ronald M and Fulton, Anne B and Moskowitz, Anne and Calabrese, Carly E and Dagi, Linda R}
}
@article {1586198,
	title = {Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study},
	journal = {Acta Ophthalmol},
	volume = {99},
	number = {6},
	year = {2021},
	month = {2021 Sep},
	pages = {669-678},
	abstract = {PURPOSE: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. METHODS: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). RESULTS: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission\&nbsp;>=\&nbsp;2\&nbsp;years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. CONCLUSIONS: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.},
	issn = {1755-3768},
	doi = {10.1111/aos.14702},
	author = {Nguyen, Quan Dong and Anesi, Stephen D and Chexal, Saradha and Chu, David S and Dayani, Pouya N and Leng, Theodore and Meleth, Annal D and Sallam, Ahmed A and Sheppard, John D and Silverstein, Steven M and Toyos, Melissa and Wang, Robert C and Foster, Charles Stephen}
}
@article {1677766,
	title = {Therapeutic activation of endothelial sphingosine-1-phosphate receptor 1 by chaperone-bound S1P suppresses proliferative retinal neovascularization},
	journal = {EMBO Mol Med},
	volume = {15},
	number = {5},
	year = {2023},
	month = {2023 May 08},
	pages = {e16645},
	abstract = {Sphingosine-1-phosphate (S1P), the circulating HDL-bound lipid mediator that acts via S1P receptors (S1PR), is required for normal vascular development. The role of this signaling axis in vascular retinopathies is unclear. Here, we show in a mouse model of oxygen-induced retinopathy (OIR) that endothelial overexpression of S1pr1 suppresses while endothelial knockout of S1pr1 worsens neovascular tuft formation. Furthermore, neovascular tufts are increased in Apom-/- mice which lack HDL-bound S1P while they are suppressed in ApomTG mice which have more circulating HDL-S1P. These results suggest that circulating HDL-S1P activation of endothelial S1PR1 suppresses neovascular pathology in OIR. Additionally, systemic administration of ApoM-Fc-bound S1P or a small-molecule Gi-biased S1PR1 agonist suppressed neovascular tuft formation. Circulating HDL-S1P activation of endothelial S1PR1 may be a key protective mechanism to guard against neovascular retinopathies that occur not only in premature infants but also in diabetic patients and aging people.},
	keywords = {Animals, Lipoproteins, HDL, Lysophospholipids, Mice, Receptors, Lysosphingolipid, Retinal Neovascularization, Sphingosine, Sphingosine-1-Phosphate Receptors},
	issn = {1757-4684},
	doi = {10.15252/emmm.202216645},
	author = {Niaudet, Colin and Jung, Bongnam and Kuo, Andrew and Swendeman, Steven and Bull, Edward and Seno, Takahiro and Crocker, Reed and Fu, Zhongjie and Smith, Lois E H and Hla, Timothy}
}
@article {1363165,
	title = {Anterior uveitis secondary to type II essential cryoglobulinemia},
	journal = {J Ophthalmic Inflamm Infect},
	volume = {3},
	number = {1},
	year = {2013},
	month = {2013 Jul 25},
	pages = {56},
	abstract = {BACKGROUND: The purpose of this report is to describe the association of severe anterior uveitis with type II essential cryoglobulinemia. FINDINGS: A 40-year-old male with a history of psoriatic arthritis presented with severe anterior uveitis associated with type II essential cryoglobulinemia. His uveitis, refractory to steroid treatments, was well controlled following treatments for cryoglobulinemia. The temporal association between his cryoglobulinemia and uveitis, combined with his improved visual acuity and inflammation after plasmapheresis and rituximab infusions, suggests cryoglobulinemia to be the underlying condition of his uveitis. CONCLUSIONS: To our best knowledge, this is the first reported case of anterior uveitis secondary to type II essential cryoglobulinemia.},
	issn = {1869-5760},
	doi = {10.1186/1869-5760-3-56},
	author = {Nicholson, Laura and Sobrin, Lucia}
}
@article {1635622,
	title = {Multimodal treatment of Coats-like exudative vitreoretinopathy in Goldmann-Favre syndrome},
	journal = {Am J Ophthalmol Case Rep},
	volume = {25},
	year = {2022},
	month = {2022 Mar},
	pages = {101362},
	abstract = {Purpose: To report a Coats-like exudative vitreoretinopathy in Goldmann-Favre syndrome. Observations: A 64 year-old woman with prior diagnosis of retinal dystrophy presented with decreased vision in the right eye (OD). Ophthalmologic examination was remarkable for bilateral arteriolar attenuation, mid-peripheral bony-spicules, and waxy disc pallor. Coats-like exudative vitreoretinopathy and cystoid macular edema were present OD. Genetic testing showed a homozygous pathogenic mutation in gene NR2E3, variant c.932G\&gt;A (p.Arg311Gln), consistent with Goldmann-Favre syndrome. Targeted laser ablation and combination intravitreal therapy were effective in decreasing macular edema. Conclusions and Importance: A Coats-like exudative vitreoretinopathy may occur in the setting of Goldmann-Favre syndrome. Targeted laser ablation in combination with intravitreal therapy can be efficacious in select patients.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101362},
	author = {Nieves, Fabiola Ramos and Villegas, Victor M and Patel, Nimesh A and Berrocal, Audina M and Murray, Timothy G}
}
@article {1635628,
	title = {Dark Adaptation and Its Role in Age-Related Macular Degeneration},
	journal = {J Clin Med},
	volume = {11},
	number = {5},
	year = {2022},
	month = {2022 Mar 01},
	abstract = {Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.},
	issn = {2077-0383},
	doi = {10.3390/jcm11051358},
	author = {Nigalye, Archana K and Hess, Kristina and Pundlik, Shrinivas J and Jeffrey, Brett G and Cukras, Catherine A and Husain, Deeba}
}
@article {1598064,
	title = {Delayed dark adaptation in central serous chorioretinopathy},
	journal = {Am J Ophthalmol Case Rep},
	volume = {22},
	year = {2021},
	month = {2021 Jun},
	pages = {101098},
	abstract = {Purpose: To evaluate the effect of central serous chorioretinopathy (CSCR) on retinal function using dark adaptation in a human subject, and to follow it through resolution of the disease. Patients: Single patient, 50 years old male patient, with acute CSCR in one eye and resolved old CSCR in the other eye. Observations: Observational study in patient with CSCR followed through resolution of the subretinal fluid (52 days). Dark adaptation was assessed using the AdaptDx{\textregistered} (Maculogix Inc.) measured by Rod Intercept time (RIT) in minutes. A normal retinal locus of the same eye on the opposite side of the fovea was used as control. Retinal separation (microns) was measured using Spectralis Optical Coherence Tomography (Spectralis{\textregistered}, HRA\&nbsp;+\&nbsp;OCT, Heidelberg engineering). Change in time to dark adapt, were correlated with retinal separation measured in microns, during the course of CSCR.The Rod Intercept time was delayed in the area of detached retina compared to the normal region (control) on presentation with retinal separation (RS) of 104 μm. The Rod Intercept time returned to normal as the retinal separation from retinal pigment epithelium decreased and eventually resolved. Conclusions: This case shows that delay in dark adaptation is proportional to the amount of separation of neurosensory retina from retinal pigment epithelium in CSCR, this may offer a potential of using DA to characterize visual function in CSCR. The association of dark adaptation response with the state of retinal pigment epithelial function and its ability to predict the recurrence of CSCR needs further evaluation.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2021.101098},
	author = {Nigalye, Archana and Pundlik, Shrinivas and Kim, Janice and Luo, Gang and Husain, Deeba}
}
@article {959461,
	title = {Benchmarks for outcome indicators in pediatric cataract surgery},
	journal = {Eye (Lond)},
	volume = {31},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {417-421},
	abstract = {PurposeThe purpose of this study was to establish benchmarks for outcome indicators that may help ascertain the quality of pediatric cataract surgery with primary intraocular lens (IOL) implantation.Patients and methodsA retrospective chart review of patients older than 2 years undergoing cataract surgery with primary IOL implantation, by multiple surgeons in a tertiary-care center, from November 2005 to February 2016 was conducted. Patients with ocular comorbidities that would affect the outcomes were excluded. The outcome measures chosen were as follows: (1) final best corrected Snellen visual acuity (BCVA) in patients who had bilateral cataract surgery analyzed at the last clinic visit; (2) prediction error (PE)=expected refraction-actual refraction. Mean PE and mean absolute PE were assessed 1 month postoperatively, irrespective of age or laterality.ResultsMean age at surgery was 8.3{\textpm}4.6 years and mean follow-up duration was 3.7{\textpm}2.7 years. The results of outcome measures were as follows: (1) BCVA was 20/40 or better in 96\% (n=124 eyes, mean patient age: 8.3{\textpm}4.6 years). Remaining five eyes had amblyopia with two eyes having BCVA worse than 20/100 that did not respond to amblyopia treatment. (2) Mean PE was 0.3{\textpm}1.1 D and mean absolute PE was 0.9{\textpm}0.7 D. PE was within {\textpm}0.5 D in 43.0\%, {\textpm}1.0 D in 66\%, and {\textpm}2.0 D in 95\% (n=235 eyes).ConclusionGood visual acuity after cataract surgery should be expected for children with bilateral cataracts, setting a high benchmark similar to that recommended in adult cataract surgery. Prediction error is greater in pediatric eyes than in adult eyes, setting a lower benchmark. This study establishes benchmark for outcome indicators in pediatric patients older than 2 years undergoing cataract surgery with primary IOL implantation.},
	issn = {1476-5454},
	doi = {10.1038/eye.2016.240},
	author = {Nihalani, B R and VanderVeen, D K}
}
@article {1302183,
	title = {Long-chain polyunsaturated fatty acids decline rapidly in milk from mothers delivering extremely preterm indicating the need for supplementation},
	journal = {Acta Paediatr},
	volume = {107},
	number = {6},
	year = {2018},
	month = {2018 Jun},
	pages = {1020-1027},
	abstract = {AIM: Our aim was to perform an in-depth analysis of the composition of fatty acids in milk from mothers delivering extremely preterm babies. We investigated longitudinal changes in milk fatty acid profiles and the relationship between several types of fatty acids, including omega-3 and omega-6.

METHODS: Milk samples were collected at three stages of lactation from 78 mothers who delivered at less than 28~weeks of pregnancy at the Sahlgrenska University Hospital, Gothenburg, Sweden, from April 2013 to September 2015. Fatty acid composition was analysed by gas chromatography-mass spectrometry.

RESULTS: A reduction in long-chain polyunsaturated fatty acids (LCPUFAs) was observed during the lactation period. The concentrations of arachidonic acid and docosahexaenoic acid declined from medians of 0.34 to 0.22~mol\% and 0.29 to 0.15~mol\%, respectively, between postnatal day 7 and a postmenstrual age of 40~weeks. Strong correlations were found between the intermediates of several classes of fatty acids, including omega-3, omega-6 and omega-9.

CONCLUSION: A rapid reduction in LCPUFA content in the mother{\textquoteright}s milk during the lactation period emphasises the importance of fatty acid supplementation to infants born extremely preterm, at least during the period corresponding to the third trimester, when rapid development of the brain and adipose tissue requires high levels of LCPUFAs.},
	issn = {1651-2227},
	doi = {10.1111/apa.14275},
	author = {Nilsson, Anders K and L{\"o}fqvist, Chatarina and Najm, Svetlana and Hellgren, Gunnel and S{\"a}vman, Karin and Andersson, Mats X and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1589752,
	title = {Sphingolipidomics of serum in extremely preterm infants: Association between low sphingosine-1-phosphate levels and severe retinopathy of prematurity},
	journal = {Biochim Biophys Acta Mol Cell Biol Lipids},
	volume = {1866},
	number = {7},
	year = {2021},
	month = {2021 Jul},
	pages = {158939},
	abstract = {BACKGROUND: Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP) that can cause impaired vision or blindness. Changes in blood lipids have been associated with ROP. This study aimed to monitor longitudinal changes in the serum sphingolipidome of extremely preterm infants and investigate the relationship to development of severe ROP. METHODS: This is a prospective study that included 47 infants born \&lt;28 gestational weeks. Serum samples were collected from cord blood and at postnatal days 1, 7, 14, and 28, and at postmenstrual weeks (PMW) 32, 36, and 40. Serum sphingolipids and phosphatidylcholines were extracted and analyzed by LC-MS/MS. Associations between sphingolipid species and ROP were assessed using mixed models for repeated measures. RESULTS: The serum concentration of all investigated lipid classes, including ceramide, mono- di- and trihexosylceramide, sphingomyelin, and phosphatidylcholine displayed distinct temporal patterns between birth and PMW40. There were also substantial changes in the lipid species composition within each class. Among the analyzed sphingolipid species, sphingosine-1-phosphate showed the strongest association with severe ROP, and this association was independent of gestational age at birth and weight standard deviation score change. CONCLUSIONS: The serum phospho- and sphingolipidome undergoes significant remodeling during the first weeks of the preterm infant{\textquoteright}s life. Low postnatal levels of the signaling lipid sphingosine-1-phosphate are associated with the development of severe ROP.},
	issn = {1879-2618},
	doi = {10.1016/j.bbalip.2021.158939},
	author = {Nilsson, Anders K and Andersson, Mats X and Sj{\"o}bom, Ulrika and Hellgren, Gunnel and Lundgren, Pia and Pivodic, Aldina and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1309952,
	title = {Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants},
	journal = {JPEN J Parenter Enteral Nutr},
	volume = {43},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {152-161},
	abstract = {BACKGROUND: Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). We investigated how fatty acids from breast milk and parenteral lipid emulsions shape serum LC-PUFA profiles in extremely preterm infants during early perinatal life. METHODS: Ninety infants born \&lt; 28 weeks gestational age were randomized to receive parenteral lipids with or without the ω-3 LC-PUFAs eicosapentaenoic acid (EPA) and DHA (SMOFlipid: Fresenius Kabi, Uppsala, Sweden, or Clinoleic: Baxter Medical AB, Kista, Sweden, respectively). The fatty acid composition of infant serum phospholipids was determined from birth to postmenstrual age 40 weeks, and in mother{\textquoteright}s milk total lipids on postnatal day 7. Enteral and parenteral intake of LC-PUFAs was correlated with levels in infant serum. RESULTS: Infants administered parenteral ω-3 LC-PUFAs received 4.4 and 19.3 times more DHA and EPA, respectively, over the first 2 weeks of life. Parenteral EPA but not DHA correlated with levels in infant serum. We found linear relationships between dietary EPA and DHA and infant serum levels in the Clinoleic (Baxter Medical AB) group. The volume of administered SMOFlipid (Fresenius Kabi) was inversely correlated with serum AA, whereas Clinoleic (Baxter Medical AB) inversely correlated with serum EPA and DHA. CONCLUSIONS: There appears to be no or low correlation between the amount of DHA administered parenterally and levels measured in serum. Whether this observation reflects serum phospholipid fraction only or truly represents the amount of accreted DHA needs to be investigated. None of the parenteral lipid emulsions satisfactorily maintained high levels of both ω-6 and ω-3 LC-PUFAs in infant serum.},
	issn = {1941-2444},
	doi = {10.1002/jpen.1172},
	author = {Nilsson, Anders K and L{\"o}fqvist, Chatarina and Najm, Svetlana and Hellgren, Gunnel and S{\"a}vman, Karin and Andersson, Mats X and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1559531,
	title = {Defective INPP5E distribution in NPHP1-related Senior-Loken syndrome},
	journal = {Mol Genet Genomic Med},
	year = {2020},
	month = {2020 Dec 11},
	pages = {e1566},
	abstract = {BACKGROUND: Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protein nephrocystin-1, which functions at the transition zone (TZ) of primary cilia. METHODS: We report a 9-year-old Senior-Loken syndrome boy with NPHP1 deletion, who presents with bilateral vision decrease and cystic renal disease. Renal function deteriorated to require bilateral nephrectomy and renal transplant. We performed immunohistochemistry, H\&amp;E staining, and electron microscopy on the renal sample to determine the subcellular distribution of ciliary proteins in the absence of NPHP1. RESULTS: Immunohistochemistry and electron microscopy of the resected kidney showed disorganized cystic structures with loss of cilia in renal tubules. Phosphoinositides have been recently recognized as critical components of the ciliary membrane and immunostaining of kidney sections for phosphoinositide 5-phosphatase, INPP5E, showed loss of staining compared to healthy control. Ophthalmic examination showed decreased electroretinogram consistent with early retinal degeneration. CONCLUSION: The decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 that it is involved in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells.},
	issn = {2324-9269},
	doi = {10.1002/mgg3.1566},
	author = {Ning, Ke and Song, Emilie and Sendayen, Brent E and Prosseda, Philipp P and Chang, Kun-Che and Ghaffarieh, Alireza and Alvarado, Jorge A and Wang, Biao and Haider, Kathryn M and Berbari, Nicolas F and Hu, Yang and Sun, Yang}
}
@article {1319474,
	title = {Color-selective photophobia in ictal vs interictal migraineurs and in healthy controls},
	journal = {Pain},
	volume = {159},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {2030-2034},
	abstract = {Aversion to light is common among migraineurs undergoing acute attacks. Using psychophysical assessments in patients with episodic migraine, we reported that white, blue, amber, and red lights exacerbate migraine headache in a significantly larger percentage of patients and to a greater extent compared with green light. This study aimed at determining whether these findings are phase-dependent-namely, manifested exclusively during migraine (ictally) but not in its absence (interictally), or condition-dependent-ie, expressed uniquely in migraineurs but not in healthy controls. To determine whether the color preference of migraine-type photophobia is phase- or condition-dependent, we compared the effects of each color of light in each intensity between migraineurs during and in-between attacks and healthy controls. During the ictal and interictal phases, the proportion of migraineurs reporting changes in headache severity when exposed to the different colors of light increased in accordance with elevated light intensities. During the ictal phase, white, blue, amber, and red lights exacerbated headaches in \~{}80\% of the patients; however, during the interictal phase, light initiated headache in only 16\% to 19\%. Notably, green light exacerbated headaches in 40\% and triggered headaches in 3\% of the patients studied during the ictal and interictal phases, respectively. With one exception (highest red light intensity), no control subject reported headache in response to the light stimuli. These findings suggest that color preference is unique to migraineurs-as it was not found in control subjects-and that it is independent of whether or not the patients are in their ictal or interictal phase.},
	issn = {1872-6623},
	doi = {10.1097/j.pain.0000000000001303},
	author = {Nir, Rony-Reuven and Lee, Alice J and Huntington, Shaelah and Noseda, Rodrigo and Bernstein, Carolyn A and Fulton, Anne B and Bertisch, Suzanne M and Hovaguimian, Alexandra and Buettner, Catherine and Borsook, David and Burstein, Rami}
}
@article {1677801,
	title = {Transscleral vs endoscopic cyclophotocoagulation: safety and efficacy when combined with phacoemulsification},
	journal = {BMC Ophthalmol},
	volume = {23},
	number = {1},
	year = {2023},
	month = {2023 Mar 30},
	pages = {129},
	abstract = {PURPOSE: To compare the effectiveness and safety of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation (phaco/MP-TSCPC), and phacoemulsification alone (phaco) in the treatment of coexisting cataract and glaucoma. METHODS: Retrospective cohort study of consecutive cases at Massachusetts Eye \&amp; Ear. The main outcome measures were the cumulative probabilities of failure between the phaco/ECP group, phaco/MP-TSCPC group, and the phaco alone group with failure defined as reaching NLP vision at any point postoperatively, undergoing\&nbsp;additional\&nbsp;glaucoma surgery,\&nbsp;or the inability to maintain >= 20\% IOP reduction from baseline with IOP between 5-18\&nbsp;mmHg\&nbsp;while maintaining\&nbsp;<= baseline medications. Additional outcome measures included changes in average IOP, number of glaucoma medications, and complication rates. RESULTS: Sixty-four eyes from 64 patients (25 phaco/ECP, 20 phaco/MPTSCPC, 19 phaco alone) were included in this study. The groups did not differ in age (mean 71.04 {\textpm} 6.7\&nbsp;years) or length of follow-up time. Baseline IOPs were significantly different between groups (15.78 {\textpm} 4.7\&nbsp;mmHg phaco/ECP, 18.37 {\textpm} 4.6\&nbsp;mmHg phaco/MP-TSCPC, 14.30 {\textpm} 4.2\&nbsp;mmHg phaco alone, p = 0.02). Primary open-angle glaucoma was the most common type of glaucoma in the phaco alone (42\%) and phaco/ECP (48\%) groups while mixed-mechanism glaucoma was the most common type in the phaco/MP-TSCPC group (40\%). Surgical failure was less likely in eyes in the phaco/MP-TSCPC (3.40 times, p = 0.005) and phaco/ECP (1.40 times, p = 0.044) groups compared to phaco alone based on the Kaplan-Meier survival criteria. These differences maintained statistical significance when differences in preoperative IOP were taken into account using the Cox PH model (p = 0.011 and p = 0.004, respectively). Additionally, surgical failure was 1.98 times less likely following phaco/MP-TSCPC compared to phaco/ECP (p = 0.038). This difference only approached significance once differences in preoperative IOP were accounted for (p = 0.052). There was no significant difference in IOP reduction at 1\&nbsp;year between groups. Mean IOP reductions at 1\&nbsp;year were 3.07 {\textpm} 5.3\&nbsp;mmHg from a baseline of 15.78 {\textpm} 4.7 in the phaco/ECP group, 6.0 {\textpm} 4.3\&nbsp;mmHg from a baseline of 18.37 {\textpm} 4.6 in the phaco/MP-TSCPC group and 1.0 {\textpm} 1.6 from a baseline of 14.30 {\textpm} 4.2\&nbsp;mmHg in the phaco alone group.\&nbsp;There were no differences in complication\&nbsp;rates among the three groups. CONCLUSIONS: Both Phaco/MP-TSCPC and phaco/ECP appear to provide superior efficacy for IOP control when compared to phaco alone. All three procedures had similar safety profiles.},
	issn = {1471-2415},
	doi = {10.1186/s12886-023-02877-6},
	author = {Nirappel, Abraham and Klug, Emma and Neeson, Cameron and Chachanidze, Mari and El Helwe, Hani and Hall, Nathan and Chang, Ta C and Shen, Lucy Q and Sol{\'a}-Del Valle, David}
}
@article {1645463,
	title = {A woman with white deposits in her eye},
	journal = {BMJ},
	volume = {377},
	year = {2022},
	month = {2022 06 16},
	pages = {e067966},
	keywords = {Corneal Diseases, Female, Humans},
	issn = {1756-1833},
	doi = {10.1136/bmj-2021-067966},
	author = {Nirappel, Abraham and Anand, Nandita and Del Valle, David Sol{\'a} and Soneru, Allison}
}
@article {1549019,
	title = {TNFα activates MAPK and Jak-Stat pathways to promote mouse M{\"u}ller cell proliferation},
	journal = {Exp Eye Res},
	volume = {202},
	year = {2021},
	month = {2021 Jan},
	pages = {108353},
	abstract = {Mouse M{\"u}ller cells, considered as dormant retinal progenitors, often respond to retinal injury by undergoing reactive gliosis rather than displaying neural regenerative responses. Tumor necrosis factor alpha (TNFα) is a key cytokines induced after injury and implicated in mediating inflammatory and neural regenerative responses in zebrafish. To investigate the involvement of TNFα in mouse retinal injury, adult C57BL/6J mice were subjected to light damage for 14 consecutive days. TNFα was elevated in the retina of mice exposed to light damage, which induced M{\"u}ller cell proliferation in vitro. Affymetrix microarray showed that, in M{\"u}ller cells, TNFα induces up-regulation of inflammatory and proliferation-related genes, including NFKB2, leukemia inhibitory factor, interleukin-6, janus kinase (Jak) 1, Jak2, signal transducer and activator of transcription (Stat) 1, Stat2, mitogen-activated protein kinase (MAPK) 7, and MAP4K4 but down-regulation of neuroprogenitor genes, including Sox9, Ascl1, Wnt2 and Hes1. Blocking the Jak/Stat and MAPK pathways attenuated TNFα-induced M{\"u}ller cell proliferation. These results suggest that TNFα may drive the proliferation and inflammatory response, rather than the neural regenerative potential, of mouse M{\"u}ller cells.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.108353},
	author = {Niu, Liangliang and Fang, Yuan and Yao, Xiaoqian and Zhang, Yi and Wu, Jihong and Chen, Dong Feng and Sun, Xinghuai}
}
@article {1435410,
	title = {Ocular Adverse Events following Use of Immune Checkpoint Inhibitors for Metastatic Malignancies},
	journal = {Ocul Immunol Inflamm},
	year = {2019},
	month = {2019 Apr 23},
	pages = {1-6},
	abstract = {PURPOSE: To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies. METHODS: Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy. RESULTS: Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs. CONCLUSION: We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2019.1583347},
	author = {Noble, Carl W and Gangaputra, Sapna S and Thompson, Ian A and Yuan, Amy and Apolo, Andrea B and Lee, Jung-Min and Papaliodis, George N and Kodati, Shilpa and Bishop, Rachel and Magone, M Teresa and Sobrin, Lucia and Sen, H Nida}
}
@article {1179211,
	title = {Exosomes mediate interepithelial transfer of functional P-glycoprotein in chronic rhinosinusitis with nasal polyps},
	journal = {Laryngoscope},
	volume = {127},
	number = {9},
	year = {2017},
	month = {2017 Sep},
	pages = {E295-E300},
	abstract = {OBJECTIVE: P-glycoprotein (P-gp) drives type-2 helper T-cell inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) through unknown posttranslational mechanisms of overexpression. A recent randomized clinical trial demonstrated that inhibition of P-gp was as effective as oral steroids and biologics in treating CRSwNP. Exosomes are 30- to 150-nm vesicles capable of intercellular membrane protein transfer. The aims of this study were 1) to determine whether CRSwNP mucus exosomes are enriched with P-gp, and 2) whether exosomal P-gp can be functionally transferred to autologous epithelial cells as a putative mechanism for the proinflammatory overexpression of P-gp in CRSwNP. STUDY DESIGN: Institutional review board-approved study in CRSwNP and control patients (n = 10 per group). METHODS: P-gp content of purified mucus exosomes was characterized by transmission electron microscopy and enzyme-linked immunosorbent assay. Epithelial transfer of exosomal P-gp was determined by time-lapse fluorescent microscopy and calcein acetoxymethylester functional P-gp assay. RESULTS: CD63+/P-gp+ exosomes were detected in both groups. P-gp was significantly enriched in CRSwNP exosomes relative to control (median 198.5; interquartile range 123.6-270.5 vs. 74.4; 41.3-95.0 pcg P-gp/10(9) exosomes, P = 0.002). Exosomes were absorbed by epithelial cells within 10 minutes, resulting in a significant increase in P-gp activity in CRSwNP patients relative to control (P = 0.006). CONCLUSION: Here we demonstrate the presence and P-gp enrichment of mucus-derived exosomes, or rhinosomes, in CRSwNP. These rhinosomes are capable of rapid intercellular transfer of P-gp, leading to increased P-gp function within recipient cells. This represents a novel mechanism for maintaining P-gp overexpression in CRSwNP, and more generally for interepithelial transfer of other proteins between mucosal epithelial cells. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E295-E300, 2017.},
	keywords = {Adult, Aged, Case-Control Studies, Cell Communication, Chronic Disease, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Exosomes, Female, Humans, Male, Middle Aged, Nasal Mucosa, Nasal Polyps, P-Glycoprotein, Rhinitis, Sinusitis, Young Adult},
	issn = {1531-4995},
	doi = {10.1002/lary.26614},
	author = {Nocera, Angela L and Miyake, Marcel M and Seifert, Philip and Han, Xue and Bleier, Benjamin S}
}
@article {1435411,
	title = {Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide},
	journal = {J Allergy Clin Immunol},
	volume = {143},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {1525-1535.e1},
	abstract = {BACKGROUND: Nasal mucosa-derived exosomes (NMDEs) harbor immunodefensive proteins and are capable of rapid interepithelial protein transfer. OBJECTIVES: We sought to determine whether mucosal exposure to inhaled pathogens stimulates a defensive swarm of microbiocidal exosomes, which also donate their antimicrobial cargo to adjacent epithelial cells. METHODS: We performed an institutional review board-approved study of healthy NMDE secretion after Toll-like receptor (TLR) 4 stimulation by LPS (12.5\&nbsp;μg/mL) in the presence of TLR4 inhibitors. Interepithelial transfer of exosomal nitric oxide (NO) synthase and nitric oxide was measured by using ELISAs and NO activity assays. Exosomal antimicrobial assays were performed with Pseudomonas aeruginosa. Proteomic analyses were performed by using SOMAscan. RESULTS: In\&nbsp;vivo and in\&nbsp;vitro LPS exposure induced a 2-fold increase in NMDE secretion along with a 2-fold increase in exosomal inducible nitric oxide synthase expression and function through TLR4 and inhibitor of nuclear factor κB kinase activation. LPS stimulation increased exosomal microbiocidal activity against P aeruginosa by almost 2 orders of magnitude. LPS-stimulated exosomes induced a 4-fold increase in NO production within autologous epithelial cells with protein transfer within 5\&nbsp;minutes of contact. Pathway analysis of the NMDE proteome revealed 44 additional proteins associated with NO signaling and innate immune function. CONCLUSIONS: We provide direct in\&nbsp;vivo evidence for a novel exosome-mediated innate immunosurveillance and defense mechanism of the human upper airway. These findings have implications for lower airway innate immunity, delivery of airway therapeutics, and host microbiome regulation.},
	issn = {1097-6825},
	doi = {10.1016/j.jaci.2018.08.046},
	author = {Nocera, Angela L and Mueller, Sarina K and Stephan, Jules R and Hing, Loretta and Seifert, Philip and Han, Xue and Lin, Derrick T and Amiji, Mansoor M and Libermann, Towia and Bleier, Benjamin S}
}
@article {1424811,
	title = {"Plugged In"},
	journal = {Orbit},
	volume = {39},
	number = {1},
	year = {2020},
	month = {2020 Feb},
	pages = {73-74},
	issn = {1744-5108},
	doi = {10.1080/01676830.2019.1576742},
	author = {Nolan, John G and Vestal, Matthew and Stone, Scellig and Dagi, Linda R}
}
@article {1655715,
	title = {Elk-1 regulates retinal ganglion cell axon regeneration after injury},
	journal = {Sci Rep},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 Oct 19},
	pages = {17446},
	abstract = {Adult central nervous system (CNS) axons fail to regenerate after injury, and master regulators of the regenerative program remain to be identified. We analyzed the transcriptomes of retinal ganglion cells (RGCs) at 1 and 5\&nbsp;days after optic nerve injury with and without a cocktail of strongly pro-regenerative factors to discover genes that regulate survival and regeneration. We used advanced bioinformatic analysis to identify the top transcriptional regulators of upstream genes and cross-referenced these with the regulators upstream of genes differentially expressed between embryonic RGCs that exhibit robust axon growth vs. postnatal RGCs where this potential has been lost. We established the transcriptional activator Elk-1 as the top regulator of RGC gene expression associated with axon outgrowth in both models. We demonstrate that Elk-1 is necessary and sufficient to promote RGC neuroprotection and regeneration in vivo, and is enhanced by manipulating specific phosphorylation sites. Finally, we co-manipulated Elk-1, PTEN, and REST, another transcription factor discovered in our analysis, and found Elk-1 to be downstream of PTEN and inhibited by REST in the survival and axon regenerative pathway in RGCs. These results uncover the basic mechanisms of regulation of survival and axon growth and reveal a novel, potent therapeutic strategy to promote neuroprotection and regeneration in the adult CNS.},
	keywords = {Axons, Humans, Nerve Regeneration, Optic Nerve Injuries, Retinal Ganglion Cells, Transcription Factors},
	issn = {2045-2322},
	doi = {10.1038/s41598-022-21767-3},
	author = {Noro, Takahiko and Shah, Sahil H and Yin, Yuqin and Kawaguchi, Riki and Yokota, Satoshi and Chang, Kun-Che and Madaan, Ankush and Sun, Catalina and Coppola, Giovanni and Geschwind, Daniel and Benowitz, Larry I and Goldberg, Jeffrey L}
}
@article {1586159,
	title = {Process development and safety evaluation of ABCB5 limbal stem cells as advanced-therapy medicinal product to treat limbal stem cell deficiency},
	journal = {Stem Cell Res Ther},
	volume = {12},
	number = {1},
	year = {2021},
	month = {2021 Mar 19},
	pages = {194},
	abstract = {BACKGROUND: While therapeutic success of the limbal tissue or cell transplantation to treat severe cases of limbal stem cell (LSC) deficiency (LSCD) strongly depends on the percentage of LSCs within the transplanted cells, prospective LSC enrichment has been hampered by the intranuclear localization of the previously reported LSC marker p63. The recent identification of the ATP-binding cassette transporter ABCB5 as a plasma membrane-spanning marker of LSCs that are capable of restoring the cornea and the development of an antibody directed against an extracellular loop of the ABCB5 molecule stimulated us to develop a novel treatment strategy based on the utilization of in vitro expanded allogeneic ABCB5 LSCs derived from human cadaveric limbal tissue. METHODS: We developed and validated a Good Manufacturing Practice- and European Pharmacopeia-conform production and quality-control process, by which ABCB5 LSCs are derived from human corneal rims, expanded ex vivo, isolated as homogenous cell population, and manufactured as an advanced-therapy medicinal product (ATMP). This product was tested in a preclinical study program investigating the cells{\textquoteright} engraftment potential, biodistribution behavior, and safety. RESULTS: ABCB5 LSCs were reliably expanded and manufactured as an ATMP that contains comparably high percentages of cells expressing transcription factors critical for LSC stemness maintenance (p63) and corneal epithelial differentiation (PAX6). Preclinical studies confirmed local engraftment potential of the cells and gave no signals of toxicity and tumorgenicity. These findings were sufficient for the product to be approved by the German Paul Ehrlich Institute and the U.S. Food \&amp; Drug Administration to be tested in an international multicenter phase I/IIa clinical trial (NCT03549299) to evaluate the safety and therapeutic efficacy in patients with LSCD. CONCLUSION: Building upon these data in conjunction with the previously shown cornea-restoring capacity of human ABCB5 LSCs in animal models of LSCD, we provide an advanced allogeneic LSC-based treatment strategy that shows promise for replenishment of the patient{\textquoteright}s LSC pool, recreation of a functional barrier against invading conjunctival cells and restoration of a transparent, avascular cornea.},
	issn = {1757-6512},
	doi = {10.1186/s13287-021-02272-2},
	author = {Norrick, Alexandra and Esterlechner, Jasmina and Niebergall-Roth, Elke and Dehio, Ulf and Sadeghi, Samar and Schr{\"o}der, Hannes M and Ballikaya, Seda and Stemler, Nicole and Ganss, Christoph and Dieter, Kathrin and Dachtler, Ann-Kathrin and Merz, Patrick and Sel, Saadettin and Chodosh, James and Cursiefen, Claus and Frank, Natasha Y and Auffarth, Gerd U and Ksander, Bruce and Frank, Markus H and Kluth, Mark A}
}
@article {1138376,
	title = {Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others},
	journal = {Neuron},
	volume = {94},
	number = {6},
	year = {2017},
	month = {2017 Jun 21},
	pages = {1112-1120.e4},
	abstract = {At least 30 types of retinal ganglion cells (RGCs) send\&nbsp;distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here\&nbsp;we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration\&nbsp;of other types. From a screen of transcription factors, we identified Sox11 as one that could induce\&nbsp;substantial axon regeneration. Transcriptome\&nbsp;profiling indicated that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, α-RGCs, which preferentially regenerate following treatments such as Pten deletion, were killed by Sox11 overexpression. Thus, Sox11 promotes regeneration of non-α-RGCs, which are refractory to Pten deletion-induced regeneration.\&nbsp;We conclude that Sox11 can reprogram adult RGCs to a growth-competent state, suggesting that different growth-promoting interventions promote regeneration in distinct neuronal types.},
	keywords = {Animals, Axons, Cell Survival, Gene Expression Profiling, Mice, Microscopy, Fluorescence, Nerve Regeneration, Neuronal Outgrowth, Optic Nerve Injuries, PTEN Phosphohydrolase, Regeneration, Retina, Retinal Ganglion Cells, SOXC Transcription Factors},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2017.05.035},
	author = {Norsworthy, Michael W and Bei, Fengfeng and Kawaguchi, Riki and Wang, Qing and Tran, Nicholas M and Li, Yi and Brommer, Benedikt and Zhang, Yiming and Wang, Chen and Sanes, Joshua R and Coppola, Giovanni and He, Zhigang}
}
@article {1430534,
	title = {Merkel Cell Carcinoma of the Eyelid: a Review},
	journal = {Surv Ophthalmol},
	year = {2019},
	month = {2019 Mar 11},
	abstract = {Merkel cell carcinoma (MCC) is a rare, aggressive tumor of both epithelial and neuroendocrine origin that carries a mortality rate of up to 40\%. MCC tumors typically present as painless, expanding nodules on the sun-exposed skin areas of older, white patients. Eyelid and periocular tumors comprise approximately 2.5\% of all cases of MCC and may be mistaken for chalazia or basal cell carcinomas. Immunosuppression is a significant risk factor, particularly in solid-organ transplant recipients, patients with chronic lymphocytic leukemia, and patients with HIV. Sentinel lymph node biopsy is often employed for accurate staging of head and neck MCC. Treatment includes wide-local excision, commonly with the addition of radiotherapy for improved locoregional disease control. Historically, adjuvant chemotherapy had been reserved for metastatic disease, but immunotherapy and targeted chemotherapies are currently being investigated for use in primary disease. The clinical characteristics of all available published cases of eyelid MCC are summarized .},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2019.03.002},
	author = {North, Victoria S and Habib, Larissa and Yoon, Michael K}
}
@article {1559564,
	title = {Lower eyelid malposition following repair of complex orbitofacial trauma},
	journal = {Orbit},
	volume = {41},
	number = {2},
	year = {2022},
	month = {2022 Apr},
	pages = {193-198},
	abstract = {PURPOSE: To compare the incidence of lower eyelid malposition following repair of isolated orbital floor fractures with that of complex orbitofacial fractures (defined as multi-wall fractures or prior orbital fracture repairs requiring revision) by oculofacial plastic surgeons via a transconjunctival or swinging eyelid approach. METHODS: Retrospective review of 175 patients who underwent surgical repair of orbital fractures at our institution. The primary outcomes were the occurrence of lower eyelid malposition (ectropion, entropion, and eyelid retraction) and the need for subsequent surgical correction. RESULTS: Of 95 patients with isolated orbital floor fractures, 4 developed eyelid malposition (4.2\%), 1 of which required surgical repair (1.1\%). Of 80 patients with complex orbitofacial fractures (48 multi-wall fractures, 32 secondary revisions), 10 had pre-operative eyelid malposition and were excluded from further analysis. Fourteen of the remaining 70 patients developed postoperative eyelid malposition (20\%), 3 of which required surgical repair (4.3\%). The difference in the occurrence of eyelid malposition between groups was statistically significant (p =\&nbsp;.001), but the difference in rates of those requiring subsequent repair was not (p =\&nbsp;.182). There was no statistically significant difference in the occurrence of eyelid malposition when considering other surgical factors including lateral canthotomy, conjunctival closure, implant material, or anterior rim screws. CONCLUSIONS: The incidence of lower eyelid malposition following orbital fracture repair via a fornix-based approach was significantly higher for the repair of complex orbitofacial fractures than for isolated floor fractures. However, very few patients in either group required surgical repair for eyelid malposition. Surgical factors including implant material did not affect outcomes.},
	keywords = {Ectropion, Entropion, Eyelids, Humans, Orbit, Orbital Fractures, Retrospective Studies},
	issn = {1744-5108},
	doi = {10.1080/01676830.2020.1862245},
	author = {North, Victoria S and Reshef, Edith R and Lee, Nahyoung Grace and Lefebvre, Daniel R and Freitag, Suzanne K and Yoon, Michael K}
}
@article {1789041,
	title = {Association of Patient Age and the Thyroid Eye Disease-Clinical Activity Score},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {6S},
	year = {2023},
	month = {2023 Dec 01},
	pages = {S46-S50},
	abstract = {PURPOSE: To investigate the association between age and clinical activity score (CAS) in patients with active, untreated thyroid eye disease. METHODS: A retrospective review was conducted of patients with active, untreated thyroid eye disease at a single institution between 2010 and 2020 whose ophthalmologic symptoms began no more than 9 months prior to the initial visit. Exclusion criteria included surgical or systemic thyroid eye disease treatment before or during the study period. Demographic and clinical data were collected for all patients, including a 7-point CAS at visit 1 (CAS1) and a 10-point score at visit 2 (CAS2). Patients were stratified by age: Group 1 (18-45), Group 2 (46-70), and Group 3 (71-85). RESULTS: A total of 156 patients were included: mean age 51.7 {\textpm} 15.8 years, 79.5\% female. CAS1 differed significantly across groups: 1.9 {\textpm} 1.0 (Group 1), 2.7 {\textpm} 1.4 (Group 2), and 2.2 {\textpm} 1.6 (Group 3), p = 0.005. Findings were similar for CAS2: 2.2 {\textpm} 1.4 (Group 1), 3.0 {\textpm} 1.8 (Group 2), and 2.8 {\textpm} 1.9 (Group 3), p = 0.030. Post hoc analysis showed a statistically significant difference between Groups 1 and 2 (p = 0.004, visit 1; p = 0.025, visit 2) but not between other pairs. Patients with CAS1 of 0-3 (n = 129) were younger on average than those with CAS1 4-7 (n = 27): 50.4 {\textpm} 16.2 versus 58.2 {\textpm} 12.8 years (p = 0.009). Conjunctival redness (p = 0.019) and chemosis (p <= 0.001) were more common in older patients at both visits. CONCLUSIONS: Patients aged 46-70 years with active, untreated thyroid eye disease had significantly higher CAS1 and CAS2 than younger patients in this study, largely driven by differences in conjunctival redness and chemosis.},
	keywords = {Adult, Aged, Female, Graves Ophthalmopathy, Humans, Male, Middle Aged, Ophthalmology},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002501},
	author = {North, Victoria S and Zhou, Henry W and Tran, Ann Q and Godfrey, Kyle J and Kazim, Michael}
}
@article {1452965,
	title = {Basal Cell Carcinoma Masquerading as a Chalazion in a 27-Year-Old Woman},
	journal = {JAMA Ophthalmol},
	volume = {137},
	number = {7},
	year = {2019},
	month = {2019 Jul 01},
	pages = {e185435},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.5435},
	author = {North, Victoria S and Starks, Victoria S and Lee, Nahyoung Grace}
}
@article {710791,
	title = {Migraine photophobia originating in cone-driven retinal pathways.},
	journal = {Brain},
	volume = {139},
	number = {Pt 7},
	year = {2016},
	month = {2016 Jul},
	pages = {1971-86},
	abstract = {Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients{\textquoteright} experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.},
	issn = {1460-2156},
	doi = {10.1093/brain/aww119},
	author = {Noseda, Rodrigo and Bernstein, Carolyn A and Nir, Rony-Reuven and Lee, Alice J and Fulton, Anne B and Bertisch, Suzanne M and Hovaguimian, Alexandra and Cestari, Dean M and Saavedra-Walker, Rodrigo and Borsook, David and Doran, Bruce L and Buettner, Catherine and Burstein, Rami}
}
@article {1474207,
	title = {Genetic LAMP2 deficiency accelerates the age-associated formation of basal laminar deposits in the retina},
	journal = {Proc Natl Acad Sci U S A},
	volume = {116},
	number = {47},
	year = {2019},
	month = {2019 Nov 19},
	pages = {23724-23734},
	abstract = {The early stages of age-related macular degeneration (AMD) are characterized by the accumulation of basal laminar deposits (BLamDs). The mechanism for BLamDs accumulating between the retinal pigment epithelium (RPE) and its basal lamina remains elusive. Here we examined the role in AMD of lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/phagosomes. LAMP2 was preferentially expressed by RPE cells, and its expression declined with age. Deletion of the gene in mice resulted in age-dependent autofluorescence abnormalities of the fundus, thickening of Bruch{\textquoteright}s membrane, and the formation of BLamDs, resembling histopathological changes occurring in AMD. Moreover, LAMP2-deficient mice developed molecular signatures similar to those found in human AMD-namely, the accumulation of APOE, APOA1, clusterin, and vitronectin-adjacent to BLamDs. In contrast, collagen 4, laminin, and fibronectin, which are extracellular matrix proteins constituting RPE basal lamina and Bruch{\textquoteright}s membrane were reduced in knockout (KO) mice. Mechanistically, retarded phagocytic degradation of photoreceptor outer segments compromised lysosomal degradation and increased exocytosis in LAMP2-deficient RPE cells. The accumulation of BLamDs observed in LAMP2-deficient mice was eventually followed by loss of the RPE and photoreceptors. Finally, we observed loss of LAMP2 expression along with ultramicroscopic features of abnormal phagocytosis and exocytosis in eyes from AMD patients but not from control individuals. Taken together, these results indicate an important role for LAMP2 in RPE function in health and disease, suggesting that LAMP2 reduction may contribute to the formation of BLamDs in AMD.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1906643116},
	author = {Notomi, Shoji and Ishihara, Kenji and Efstathiou, Nikolaos E and Lee, Jong-Jer and Hisatomi, Toshio and Tachibana, Takashi and Konstantinou, Eleni K and Ueta, Takashi and Murakami, Yusuke and Maidana, Daniel E and Ikeda, Yasuhiro and Kume, Shinji and Terasaki, Hiroto and Sonoda, Shozo and Blanz, Judith and Young, Lucy and Sakamoto, Taiji and Sonoda, Koh-Hei and Saftig, Paul and Ishibashi, Tatsuro and Miller, Joan W and Kroemer, Guido and Vavvas, Demetrios G}
}
@article {1125366,
	title = {TFOS DEWS II Clinical Trial Design Report},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {629-649},
	abstract = {The development of novel therapies for Dry Eye Disease (DED) is formidable, and relatively few treatments evaluated have been approved for marketing. In this report, the Subcommittee reviewed challenges in designing and conducting quality trials, with special reference to issues in trials in patients with DED and present the regulatory perspective on DED therapies. The Subcommittee reviewed the literature and while there are some observations about the possible reasons why so many trials have failed, there is no obvious single reason other than the lack of correlation between signs and symptoms in DED. Therefore the report advocates for conducting good quality studies, as described, going forward. A key recommendation for future studies is conduct consistent with Good Clinical Practice (GCP), including use of Good Manufacturing Practice (GMP) quality clinical trial material. The report also recommends that the design, treatments, and sample size be consistent with the investigational treatment, the objectives of the study, and the phase of development. Other recommendations for pivotal studies are a priori selection of the outcome measure, and an appropriate sample size.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.05.009},
	author = {Novack, Gary D and Asbell, Penny and Barabino, Stefano and Bergamini, Michael V W and Ciolino, Joseph B and Foulks, Gary N and Goldstein, Michael and Lemp, Michael A and Schrader, Stefan and Woods, Craig and Stapleton, Fiona}
}
@article {1318872,
	title = {Consensus guidelines for the use and interpretation of angiogenesis assays},
	journal = {Angiogenesis},
	year = {2018},
	month = {2018 May 15},
	abstract = {The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.},
	issn = {1573-7209},
	doi = {10.1007/s10456-018-9613-x},
	author = {Nowak-Sliwinska, Patrycja and Alitalo, Kari and Allen, Elizabeth and Anisimov, Andrey and Aplin, Alfred C and Auerbach, Robert and Augustin, Hellmut G and Bates, David O and van Beijnum, Judy R and Bender, R Hugh F and Bergers, Gabriele and Bikfalvi, Andreas and Bischoff, Joyce and B{\"o}ck, Barbara C and Brooks, Peter C and Bussolino, Federico and Cakir, Bertan and Carmeliet, Peter and Castranova, Daniel and Cimpean, Anca M and Cleaver, Ondine and Coukos, George and Davis, George E and De Palma, Michele and Dimberg, Anna and Dings, Ruud P M and Djonov, Valentin and Dudley, Andrew C and Dufton, Neil P and Fendt, Sarah-Maria and Ferrara, Napoleone and Fruttiger, Marcus and Fukumura, Dai and Ghesqui{\`e}re, Bart and Gong, Yan and Griffin, Robert J and Harris, Adrian L and Hughes, Christopher C W and Hultgren, Nan W and Iruela-Arispe, M Luisa and Irving, Melita and Jain, Rakesh K and Kalluri, Raghu and Kalucka, Joanna and Kerbel, Robert S and Kitajewski, Jan and Klaassen, Ingeborg and Kleinmann, Hynda K and Koolwijk, Pieter and Kuczynski, Elisabeth and Kwak, Brenda R and Marien, Koen and Melero-Martin, Juan M and Munn, Lance L and Nicosia, Roberto F and Noel, Agnes and Nurro, Jussi and Olsson, Anna-Karin and Petrova, Tatiana V and Pietras, Kristian and Pili, Roberto and Pollard, Jeffrey W and Post, Mark J and Quax, Paul H A and Rabinovich, Gabriel A and Raica, Marius and Randi, Anna M and Ribatti, Domenico and Ruegg, Curzio and Schlingemann, Reinier O and Schulte-Merker, Stefan and Smith, Lois E H and Song, Jonathan W and Stacker, Steven A and Stalin, Jimmy and Stratman, Amber N and Van de Velde, Maureen and van Hinsbergh, Victor W M and Vermeulen, Peter B and Waltenberger, Johannes and Weinstein, Brant M and Xin, Hong and Yetkin-Arik, Bahar and Yla-Herttuala, Seppo and Yoder, Mervin C and Griffioen, Arjan W}
}
@article {1761841,
	title = {Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {262},
	number = {3},
	year = {2024},
	month = {2024 Mar},
	pages = {717-752},
	abstract = {Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic.},
	keywords = {Aged, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Glucose, Humans, Hypoglycemic Agents, Macular Edema, Retrospective Studies},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06236-5},
	author = {Ntentakis, Dimitrios P and Correa, Victor San Martin Carvalho and Ntentaki, Anastasia Maria and Delavogia, Eleni and Narimatsu, Toshio and Efstathiou, Nikolaos E and Vavvas, Demetrios G}
}
@article {1817306,
	title = {Differences in effects of some newer-generation anti-diabetics on diabetic retinopathy versus nephropathy},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {262},
	number = {4},
	year = {2024},
	month = {2024 Apr},
	pages = {1371-1372},
	keywords = {Diabetes Mellitus, Type 2, Diabetic Retinopathy, Humans, Hypoglycemic Agents},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06353-1},
	author = {Ntentakis, Dimitrios Panagiotis and Corr{\^e}a, Victor San Martin Carvalho and Ntentaki, Anastasia Maria and Vavvas, Demetrios George}
}
@article {1304389,
	title = {Sutureless transscleral fixation of secondary intraocular lenses},
	journal = {Curr Opin Ophthalmol},
	volume = {29},
	number = {3},
	year = {2018},
	month = {2018 May},
	pages = {210-216},
	abstract = {PURPOSE OF REVIEW: The surgical approach to eyes needing a secondary intraocular lens have evolved rapidly in recent years. Here, we will focus on techniques for scleral-fixation of intraocular lenses (IOLs), and will review the evidence for their safety and efficacy.

RECENT FINDINGS: Transscleral fixation of IOLs refers the placement of lens haptics within scleral tunnels to stabilize the lens in eyes that lack adequate capsular support. Various surgical techniques have been reported recently to accomplish this goal. These include the use of a trocar, microvitreoretinal blade, or hypodermic needle to create the scleral tunnels, as well as several methods for placing the haptics through the tunnels. Although long-term data is lacking, each technique has been shown to have good visual outcomes without significant side effects.

SUMMARY: Surgical approaches for the transscleral fixation of secondary IOLs provide a safe and effective technique for the management of eyes with insufficient capsular support.},
	keywords = {Humans, Lens Implantation, Intraocular, Lenses, Intraocular, Postoperative Complications, Sclera, Suture Techniques, Visual Acuity},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000474},
	author = {Nudleman, Eric and Yonekawa, Yoshihiro and Prenner, Jonathan L}
}
@article {1304390,
	title = {Adherence to a mediterranean diet and its association with age-related macular degeneration. The Coimbra Eye Study-Report 4},
	journal = {Nutrition},
	volume = {51-52},
	year = {2018},
	month = {2018 Mar 13},
	pages = {6-12},
	abstract = {OBJECTIVES: This study aimed to characterize the association of lifestyle and nutritional risk profiles with age-related macular degeneration (AMD) in two subpopulations with differing AMD prevalence. METHODS: This case-control study (n = 1992) included 768 patients with AMD and 1224 age- and sex-matched participants without AMD with a single visit at a primary health care unit. Enrolled participants completed a validated lifestyle and food frequency questionnaire. A score to measure adherence to the Mediterranean diet (mediSCORE; Range, 0-9) was constructed from individual food intakes, which were further analyzed by conversion to nutrient consumption. RESULTS: Higher adherence to the Mediterranean diet (mediSCORE >=6) was significantly associated with no AMD (odds ratio [OR] = 0.73; P = 0.009). The subpopulation with lower AMD prevalence presented significantly higher adherence to the Mediterranean diet in relation to all individual food groups that comprised the mediSCORE (P \&lt; 0.014) with the exception of cereals. Food group analysis showed significant associations between the increased consumption of vegetables (OR = 0.63; P \&lt; 0.001) and fruit and nuts (OR = 0.78; P = 0.010) with no AMD. Nutrient analysis revealed that an increased ingestion of water, fibers, total fat, monounsaturated and polyunsaturated fatty acids, linoleic acid, vitamins A and C, carotene, alpha-tocopherol, folate, magnesium, iron, and zinc were significantly associated with no AMD (P \&lt; 0.0013). Finally, regular physical activity was associated with no AMD (P = 0.003). CONCLUSIONS: High adherence to a Mediterranean diet and regular physical activity seem to be protective factors for AMD in a Portuguese population. The effect of the diet is likely driven by the increased consumption of vegetables, fruits, and nuts.},
	issn = {1873-1244},
	doi = {10.1016/j.nut.2017.12.010},
	author = {Nunes, Sandrina and Alves, Dalila and Barreto, Patr{\'\i}cia and Raimundo, Miguel and da Luz Cachulo, Maria and Farinha, Cl{\'a}udia and La{\'\i}ns, In{\^e}s and Rodrigues, Jo{\~a}o and Almeida, Carlos and Ribeiro, Lu{\'\i}sa and Figueira, Jo{\~a}o and Santos, Lelita and Silva, Rufino}
}
@article {1629468,
	title = {First Visit Characteristics Associated with Future Surgery in Intermittent Exotropia},
	journal = {J Binocul Vis Ocul Motil},
	year = {2022},
	month = {2022 Jan 20},
	pages = {1-7},
	abstract = {PURPOSE: Identify demographic and clinical characteristics at the first presentation associated with later having surgery for intermittent exotropia (IXT). METHODS: Retrospective cohort study of 228 children with IXT and 5+\&nbsp;years of follow-up. Demographic and clinical data were extracted from medical records. A total 97 participants who underwent surgery during follow-up were compared to 131 participants who did not. Best subset regression was used to identify first visit variables associated with later having strabismus surgery. Surgery was then regressed on the selected variables using logistic models. RESULTS: Age and control were the only first visit variables significantly associated with having surgery for IXT. Notably, neither angle of deviation nor stereopsis were associated with later surgery. In an adjusted logistic model, each one-month increase in age at presentation was associated with a 1\% decrease in the odds of having surgery (OR\&nbsp;=\&nbsp;0.991, 95\% CI: 0.982-0.999, P =\&nbsp;.04). Children with poor control at initial visit had almost five times greater odds of having surgery than those with good control (OR\&nbsp;=\&nbsp;4.95, 95\% CI: 2.31-10.98, P \&lt;\&nbsp;.0001). CONCLUSIONS: Age and control of IXT are important factors at presentation associated with future surgical intervention for IXT. The magnitude of deviation and stereopsis was not significantly associated with future surgical treatment for IXT.},
	issn = {2576-1218},
	author = {Nwanaji-Enwerem, Jamaji C and Gateman, Taylor and Whitecross, Sarah and Whitman, Mary C}
}
@article {1360117,
	title = {Association of Long-term Ambient Black Carbon Exposure and Oxidative Stress Allelic Variants With Intraocular Pressure in Older Men},
	journal = {JAMA Ophthalmol},
	year = {2018},
	month = {2018 Nov 08},
	abstract = {Importance: Elevated intraocular pressure is a major risk factor for glaucoma, a leading cause of irreversible blindness worldwide. Environmental air pollution has been suggested as a potential contributor to elevated intraocular pressure; however, no studies have demonstrated such an association to date. Objective: To investigate the association of long-term ambient black carbon exposure with intraocular pressure in community-dwelling older adults. Design, Setting, and Participants: This population-based analysis, conducted from October 18, 2017, through March 22, 2018, used data from the all-male, New England-based Normative Aging Study of the US Department of Veterans Affairs. The analysis included 419 older men with a total of 911 follow-up study visits between January 1, 2000, and December 30, 2011. Intraocular pressure was measured by Goldmann applanation tonometry during the study visits. Validated spatiotemporal models were used to generate 1-year black carbon exposure levels at the addresses of the participants. Main Outcomes and Measures: An independently developed genetic score approach was used to calculate allelic risk scores for 3 pathways associated with black carbon toxicity: endothelial function, oxidative stress, and metal processing. The associations among black carbon exposure, allelic risk scores, and intraocular pressure were explored using linear mixed-effects models. Results: All 419 participants were men with a mean (SD) age of 75.3 (6.9) years. The mean (SD) 1-year black carbon exposure was 0.51 (0.18) μg/m3, and the mean (SD) intraocular pressure for the left eye was 14.1 (2.8) mm Hg and for the right eye was 14.1 (3.0) mm Hg. Of the 911 visits, 520 (57.1\%) had a high endothelial function allelic risk score, 644 (70.7\%) had a high metal-processing allelic risk score, and 623 (68.4\%) had a high oxidative stress allelic risk score. In fully adjusted linear mixed-effects models, the association of black carbon with intraocular pressure was greater in individuals with a high oxidative stress allelic score (β = 0.36; 95\% CI, 0.003-0.73) compared with individuals with a low score (β = -0.35; 95\% CI, -0.86 to 0.15). Conclusions and Relevance: Ambient black carbon exposure may be a risk factor for increased intraocular pressure in individuals susceptible to other biological oxidative stressors. If additional studies confirm these results, monitoring ambient black carbon exposure and physiological oxidative stress may prevent the development and progression of intraocular pressure-related disease.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.5313},
	author = {Nwanaji-Enwerem, Jamaji C and Wang, Weiye and Nwanaji-Enwerem, Onyemaechi and Vokonas, Pantel and Baccarelli, Andrea and Weisskopf, Marc and Herndon, Leon W and Wiggs, Janey L and Park, Sung Kyun and Schwartz, Joel}
}
@article {1798376,
	title = {Alzheimer{\textquoteright}s Disease: Models and Molecular Mechanisms Informing Disease and Treatments},
	journal = {Bioengineering (Basel)},
	volume = {11},
	number = {1},
	year = {2024},
	month = {2024 Jan 01},
	abstract = {Alzheimer{\textquoteright}s Disease (AD) is a complex neurodegenerative disease resulting in progressive loss of memory, language and motor abilities caused by cortical and hippocampal degeneration. This review captures the landscape of understanding of AD pathology, diagnostics, and current therapies. Two major mechanisms direct AD pathology: (1) accumulation of amyloid β (Aβ) plaque and (2) tau-derived neurofibrillary tangles (NFT). The most common variants in the Aβ pathway in APP, PSEN1, and PSEN2 are largely responsible for early-onset AD (EOAD), while MAPT, APOE, TREM2 and ABCA7 have a modifying effect on late-onset AD (LOAD). More recent studies implicate chaperone proteins and Aβ degrading proteins in AD. Several tests, such as cognitive function, brain imaging, and cerebral spinal fluid (CSF) and blood tests, are used for AD diagnosis. Additionally, several biomarkers seem to have a unique AD specific combination of expression and could potentially be used in improved, less invasive diagnostics. In addition to genetic perturbations, environmental influences, such as altered gut microbiome signatures, affect AD. Effective AD treatments have been challenging to develop. Currently, there are several FDA approved drugs (cholinesterase inhibitors, A{\ss}-targeting antibodies and an NMDA antagonist) that could mitigate AD rate of decline and symptoms of distress.},
	issn = {2306-5354},
	doi = {10.3390/bioengineering11010045},
	author = {Nystuen, Kaden L and McNamee, Shannon M and Akula, Monica and Holton, Kristina M and Deangelis, Margaret M and Haider, Neena B}
}
@article {1661591,
	title = {Distribution and Clinical Characteristics of Periorbital Infantile Hemangiomas},
	journal = {Facial Plast Surg Aesthet Med},
	volume = {25},
	number = {2},
	year = {2023},
	month = {2023 Mar-Apr},
	pages = {172-178},
	abstract = {Background: Periorbital infantile hemangiomas (POIHs) are associated with a high incidence of visual complications. Objective(s): To analyze the sites of predilection of POIHs and to determine whether certain sites require earlier intervention due to their higher rate of visual complications. Methods: A retrospective case series study was conducted on patients from two tertiary care centers for 25 years. The location of POIHs was determined from clinical photographs, medical records, and radiological studies. The presence or absence of anisometropic astigmatism (anisoastigmatism) and amblyopia was recorded. Data were analyzed using a chi-square test. Results: There were 486 patients, of which 302 patients had ophthalmology evaluations and 245 patients had refractive error data. At presentation, 10\% of patients already had amblyopia and 44\% had anisoastigmatism. Medial eyelid lesions had the highest risk of developing anisoastigmatism (anisoastigmatism correlates with eyelid position, p = 0.0001). Segmental and upper medial lesions had the highest risk of amblyopia at initial evaluation. Conclusion: The site of POIH is an important indicator for developing clinically significant anisoastigmatism and amblyopia, underlining the need for early ophthalmologic assessment and management.},
	keywords = {Amblyopia, Astigmatism, Hemangioma, Humans, Retrospective Studies, Tertiary Care Centers},
	issn = {2689-3622},
	doi = {10.1089/fpsam.2022.0099},
	author = {O, Teresa Min-Jung and Ceisler, Emily and Broude, Caroline and Chan, Kimberly and Pacicco, Lauren and Fay, Aaron and Waner, Milton}
}
@article {1367193,
	title = {The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis},
	journal = {Retina},
	volume = {34},
	number = {7},
	year = {2014},
	pages = {1451-9},
	author = {Sahin O and Ziaei A}
}
@article {1580472,
	title = {OCT Angiography Findings in Preclinical Alzheimer{\textquoteright}s Disease: 3-Year Follow-Up},
	journal = {Ophthalmology},
	volume = {128},
	number = {10},
	year = {2021},
	month = {2021 Oct},
	pages = {1489-1491},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.02.016},
	author = {O{\textquoteright}Bryhim, Bliss Elizabeth and Lin, Jonathan B and Van Stavern, Gregory P and Apte, Rajendra S}
}
@article {1319475,
	title = {Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations},
	journal = {Am J Hum Genet},
	volume = {103},
	number = {1},
	year = {2018},
	month = {2018 Jul 05},
	pages = {131-137},
	abstract = {Homozygous nonsense mutations in WNT2B were identified in three individuals from two unrelated families with severe, neonatal-onset osmotic diarrhea after whole-exome sequencing was performed on trios from the two families. Intestinal biopsy samples from affected individuals were used for histology and immunofluorescence and to generate enteroids ex\&nbsp;vivo. Histopathologic evaluation demonstrated chronic inflammatory changes in the stomach, duodenum, and colon. Immunofluorescence demonstrated diminished staining for OLFM4, a marker for intestinal stem cells (ISCs). The enteroids generated from WNT2B-deficient intestinal epithelium could not be expanded and did not survive passage. Addition of CHIR-99021 (a GSK3A and GSK3B inhibitor and activator of canonical WNT/β-CATENIN signaling) could not rescue WNT2B-deficient enteroids. Addition of supplemental recombinant murine WNT2B was able to perpetuate small enteroids for multiple passages but failed to expand their number. Enteroids showed a 10-fold increase in the expression of LEF1 mRNA and a 100-fold reduction in TLR4 expression, compared with controls by quantitative RT-PCR, indicating alterations in canonical WNT and microbial pattern-recognition signaling. In summary, individuals with homozygous nonsense mutations in WNT2B demonstrate severe intestinal dysregulation associated with decreased ISC number and function, likely\&nbsp;explaining their diarrheal phenotype. WNT2B deficiency should be considered for individuals with neonatal-onset diarrhea.},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2018.05.007},
	author = {O{\textquoteright}Connell, Amy E and Zhou, Fanny and Shah, Manasvi S and Murphy, Quinn and Rickner, Hannah and Kelsen, Judith and Boyle, John and Doyle, Jefferson J and Gangwani, Bharti and Thiagarajah, Jay R and Kamin, Daniel S and Goldsmith, Jeffrey D and Richmond, Camilla and Breault, David T and Agrawal, Pankaj B}
}
@article {1642019,
	title = {Notch Signaling in Vascular Endothelial and Mural Cell Communications},
	journal = {Cold Spring Harb Perspect Med},
	year = {2022},
	month = {2022 May 09},
	abstract = {The Notch signaling pathway is a highly versatile and evolutionarily conserved mechanism with an important role in cell fate determination. Notch signaling plays a vital role in vascular development, regulating several fundamental processes such as angiogenesis, arterial/venous differentiation, and mural cell investment. Aberrant Notch signaling can result in severe vascular phenotypes as observed in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Alagille syndrome. It is known that vascular endothelial cells and mural cells interact to regulate vessel formation, cell maturation, and stability of the vascular network. Defective endothelial-mural cell interactions are a common phenotype in diseases characterized by impaired vascular integrity. Further refinement of the role of Notch signaling in the vascular junctions will be critical to attempts to modulate Notch in the context of human vascular disease. In this review, we aim to consolidate and summarize our current understanding of Notch signaling in the vascular endothelial and mural cells during development and in the adult vasculature.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a041159},
	author = {O{\textquoteright}Hare, Michael and Arboleda-Velasquez, Joseph F}
}
@article {1589757,
	title = {Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators},
	journal = {Am J Pathol},
	volume = {191},
	number = {7},
	year = {2021},
	month = {2021 07},
	pages = {1193-1208},
	abstract = {Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-β1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in\&nbsp;vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.},
	keywords = {Angiotensin-Converting Enzyme 2, Animals, Bleomycin, Cells, Cultured, Core Binding Factor Alpha 2 Subunit, COVID-19, Disease Models, Animal, Epithelial Cells, Female, Furin, Lung, Male, Mice, Pulmonary Fibrosis, Treatment Outcome},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.04.006},
	author = {O{\textquoteright}Hare, Michael and Amarnani, Dhanesh and Whitmore, Hannah A B and An, Miranda and Marino, Claudia and Ramos, Leslie and Delgado-Tirado, Santiago and Hu, Xinyao and Chmielewska, Natalia and Chandrahas, Anita and Fitzek, Antonia and Heinrich, Fabian and Steurer, Stefan and Ondruschka, Benjamin and Glatzel, Markus and Krasemann, Susanne and Sepulveda-Falla, Diego and Lagares, David and Pedron, Julien and Bushweller, John H and Liu, Paul and Arboleda-Velasquez, Joseph F and Kim, Leo A}
}
@article {1309957,
	title = {Iontophoretic delivery of dexamethasone phosphate for non-infectious, non-necrotising anterior scleritis, dose-finding clinical trial},
	journal = {Br J Ophthalmol},
	volume = {102},
	number = {8},
	year = {2018},
	month = {2018 Aug},
	pages = {1011-1013},
	abstract = {Currently available treatment options for non-infectious scleritis, including non-steroidal anti-inflammatory drugs, systemic corticosteroids and immunosuppressive therapies, have both efficacy and side effect limitations. Iontophoretic delivery of corticosteroids has been demonstrated to be effective for anterior uveitis and represents a potential new approach to scleritis therapy. We hypothesised that iontophoretic delivery would provide effective and precise medication delivery to the sclera, while limiting systemic exposure and side effects. This first-in-human randomised, double-masked, dose-escalating study of iontophoretic administration of dexamethasone phosphate for scleritis suggests the treatment to be well tolerated and safe (within the limitations of the 18 patients sample size). There was a suggestion of efficacy in the lowest (1.2 mA/min at 0.4 mA) dose group (corresponding to the superficial location of scleritis compared with anterior uveitis), with 5/7 eyes meeting the primary efficacy outcome within 28 days. Our results suggest iontophoretic delivery of corticosteroids is a promising potential treatment for scleritis, with favourable safety and preliminary efficacy results in this phase 1 trial. TRIAL REGISTRATION NUMBER: NCT01059955.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2017-311610},
	author = {O{\textquoteright}Neil, Erin C and Huang, Jiayan and Suhler, Eric B and Dunn, James P and Perez, Victor L and Gritz, David C and McWilliams, Kathy and Peskin, Ellen and Ying, Gui-Shuang and Bunya, Vatinee Y and Maguire, Maureen G and Kempen, John H}
}
@article {1709826,
	title = {Combined MIGS: Comparing Additive Effects of Phacoemulsification, Endocyclophotocoagulation, and Kahook Dual Blade},
	journal = {Clin Ophthalmol},
	number = {17},
	year = {2023},
	pages = {1647-1659},
	author = {Oberfeld, B and Golsoorat Pahlaviani, F and Hall, N and Falah-Trzcinski, H and Trzcinski, J and Chang, T and Sol{\'a}-Del Valle, D}
}
@article {1043251,
	title = {Enhanced verbal abilities in the congenitally blind},
	journal = {Exp Brain Res},
	volume = {235},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {1709-1718},
	abstract = {Numerous studies have found that congenitally blind individuals have better verbal memory than their normally sighted counterparts. However, it is not known whether this reflects superiority of verbal or memory abilities. In order to distinguish between these possibilities, we tested congenitally blind participants and normally sighted control participants, matched for age and education, on a range of verbal and spatial tasks. Congenitally blind participants were significantly better than sighted controls on all the verbal tasks but the groups did not differ significantly on the spatial tasks. Thus, the congenitally blind appear to have superior verbal, but not spatial, abilities. This may reflect greater reliance on verbal information and the involvement of visual cortex in language processing in the congenitally blind.},
	issn = {1432-1106},
	doi = {10.1007/s00221-017-4931-6},
	author = {Occelli, Valeria and Lacey, Simon and Stephens, Careese and Merabet, Lotfi B and Sathian, K}
}
@article {591186,
	title = {Fungal Infections After Boston Type 1 Keratoprosthesis Implantation: Literature Review and In Vitro Antifungal Activity of Hypochlorous Acid.},
	journal = {Cornea},
	volume = {34},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {1599-605},
	abstract = {PURPOSE: To review the current literature describing cases of fungal keratitis and endophthalmitis after Boston keratoprosthesis (KPro) implantation and to characterize the antifungal activity of 0.01\% hypochlorous acid against medically relevant fungi. METHODS: A literature review of fungal keratitis or endophthalmitis in KPro patients from January 2001 to April 2015, and an in vitro time kill assay characterizing the fungicidal activity of 0.01\% hypochlorous acid against fungi causing ocular infections. RESULTS: Fifteen publications, predominantly retrospective case series, were identified. Infection rates after KPro implantation ranged from 0.009 to 0.02 fungal infections per patient-year of follow-up. The largest single-surgeon series reported an incidence of 2.4\% for fungal endophthalmitis during a 10-year period. Causative organisms included both yeasts and molds. Outcomes were favorable if infections were caught early and treated appropriately; less favorable outcomes were reported in developing countries where fungal species are endemic and resources are limited. 0.01\% hypochlorous acid is rapidly fungicidal, reducing the number of viable yeast cells or mold conidia by at least 99.99\% within 60 seconds. The antifungal activity extended to all molds (Acremonium kiliense, Aspergillus flavus, Aspergillus fumigatus, Fusarium solani, and Mucor indicus) and yeast species (Candida albicans and Candida parapsilosis) tested. CONCLUSIONS: Fungal infections remain a lifelong concern in patients after KPro implantation. There is a growing need for a standard antifungal prophylaxis regimen, especially in the developing world. The rapid broad-spectrum in vitro fungicidal activity of 0.01\% hypochlorous acid against all fungi tested makes it an attractive candidate as an antifungal prophylaxis in KPro patients.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000639},
	author = {Odorcic, Silvia and Haas, Wolfgang and Gilmore, Michael S and Dohlman, Claes H}
}
@article {1302198,
	title = {Efficacy and Safety of Low-Dose Iodine Plaque Brachytherapy for Juxtapapillary Choroidal Melanoma},
	journal = {Am J Ophthalmol},
	volume = {186},
	year = {2018},
	month = {2018 Feb},
	pages = {32-40},
	abstract = {PURPOSE: To evaluate low- vs high-dose plaque brachytherapy for juxtapapillary choroidal melanoma. DESIGN: Retrospective interventional case series. METHODS: Setting: Single institution. STUDY POPULATION: Forty-seven patients with juxtapapillary choroidal melanoma. INTERVENTION: Iodine-125 plaque brachytherapy. Eyes were divided into apex low-dose (LD) and high-dose (HD) groups (<= or \&gt; median apex dose 84.35 Gy). Main outcome measures were time to distant failure, local failure, death, enucleation, radiation retinopathy, optic neuropathy, and best-corrected visual acuity (BCVA). RESULTS: Freedom from distant failure rates were 96\%\&nbsp;and 95\% in apex LD and HD groups at 5 years and 77\% and 95\% at 10 years, respectively (P\&nbsp;= .84). Freedom from local failure rates were 90\% in the apex LD group vs 89\% in the HD group at 5 and 10 years (P\&nbsp;= .96). Apex LD and HD groups did not differ for time to death or enucleation. Five- and 10-year freedom from radiation retinopathy and optic neuropathy rates were higher in the apex LD than HD group. Loss of >=3\&nbsp;BCVA lines, final BCVA 20/40 or better, and final BCVA 20/200 or worse were more favorable in the 5\&nbsp;mm LD compared to HD group. Visual acuity outcomes did not differ between apex LD and HD groups. CONCLUSIONS: Low-dose iodine-125 plaque brachytherapy (67.5-81\&nbsp;Gy at tumor apex) provides safe and effective tumor control for juxtapapillary choroidal melanoma and may be associated with reduced radiation toxicity. Larger trials are needed to determine the optimal\&nbsp;therapeutic dose for juxtapapillary choroidal melanoma.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.11.008},
	author = {Oellers, Patrick and Mowery, Yvonne M and Perez, Bradford A and Stinnett, Sandra and Mettu, Pradeep and Vajzovic, Lejla and Light, Kim and Steffey, Beverly A and Cai, Jing and Dutton, Jonathan J and Buckley, Edward G and Halperin, Edward C and Marks, Lawrence B and Kirsch, David G and Mruthyunjaya, Prithvi}
}
@article {1319476,
	title = {Hemorrhagic choroidal melanoma},
	journal = {Am J Ophthalmol Case Rep},
	volume = {10},
	year = {2018},
	month = {2018 Jun},
	pages = {105-107},
	abstract = {Purpose: To demonstrate the clinical pathologic correlation in a hemorrhagic choroidal melanoma. Observations: A 52 year old patient presented with a large choroidal mass associated with vitreous and retinal hemorrhage. The eye was enucleated and histopathology demonstrated epithelioid-type MART1 positive tumor cells consistent with choroidal melanoma. The tumor had broken through Bruch{\textquoteright}s membrane, which led to localized vascular compression with bleeding into the subretinal space, retina and vitreous. Conclusions and importance: Choroidal melanoma rarely presents with hemorrhage. Tumor rupture through Bruch{\textquoteright}s membrane may result in a tourniquet effect on the tumor vasculature leading to massive hemorrhage, as in this case. A high level of clinical suspicion is required to make the diagnosis.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2018.02.001},
	author = {Oellers, Patrick and Wolkow, Natalie and Jakobiec, Frederick A and Kim, Ivana K}
}
@article {1638580,
	title = {Non-Perfusion Area Index for Prognostic Prediction in Diabetic Retinopathy},
	journal = {Life (Basel)},
	volume = {12},
	number = {4},
	year = {2022},
	month = {2022 Apr 06},
	abstract = {Fundus fluorescent angiography is a standard examination in Japan that can directly visualize the circulatory failure in diabetic retinopathy but is not used in Western countries. In this study, we examine the relationship between the non-perfusion area in fundus fluorescent angiography and the progression of diabetic retinopathy. We evaluated 22 eyes between 22 patients who had their first fundus fluorescent angiography during a clinical episode at Keio University Hospital from January 2012 to May 2015, were diagnosed as having preproliferative diabetic retinopathy, and could be followed for at least three years. The non-perfusion area index (\%) in nine segmented fundi in the initial fundus fluorescent angiography was calculated, and the progression to proliferative diabetic retinopathy over three years was evaluated. Three out of the 22 eyes (13.6\%) developed proliferative diabetic retinopathy over three years. The non-perfusion area index for the initial fundus fluorescent angiography was significantly associated with progression to proliferative diabetic retinopathy. The non-perfusion area index in the posterior pole was most strongly correlated with the progression to proliferative diabetic retinopathy. Thus, the non-perfusion area index in the posterior pole among those with preproliferative diabetic retinopathy may predict the progression to proliferative diabetic retinopathy in the subsequent three years.},
	issn = {2075-1729},
	doi = {10.3390/life12040542},
	author = {Ofuji, Yoshiko and Katada, Yusaku and Tomita, Yohei and Nagai, Norihiro and Sonobe, Hideki and Watanabe, Kazuhiro and Shinoda, Hajime and Ozawa, Yoko and Negishi, Kazuno and Tsubota, Kazuo and Kurihara, Toshihide}
}
@article {1653591,
	title = {Multicenter prospective validation study for international chronic ocular graft-versus-host disease consensus diagnostic criteria},
	journal = {Ocul Surf},
	volume = {26},
	year = {2022},
	month = {2022 Sep 18},
	pages = {200-208},
	abstract = {PURPOSE: To validate the international chronic ocular graft-versus-host disease (GVHD) diagnostic criteria (ICCGVHD) compared to the National Institute of Health diagnostic criteria 2014 (NIH2014) for chronic ocular GVHD. METHODS: Between 2013 and 2019, the study enrolled 233 patients with or without chronic ocular GVHD combined with the presence or absence of systemic chronic GVHD in an internationally prospective multicenter and observational cohort from 9 institutions. All patients were evaluated for four clinical parameters of ICCGVHD. RESULTS: The relation between the ICCGVHD score (0-11) and NIH2014 eye score (0-4) was relatively high (r\&nbsp;=\&nbsp;0.708, 95\% CI: 0.637-0.767, p\&nbsp;\&lt;\&nbsp;0.001). The sensitivity and specificity of ICCGVHD for NIH 2014 for 233 patients were 94.3\% (95\% CI: 89.6\%-98.1\%) and 71.7\% (95\% CI: 63.0-79.5\%), respectively (cutoff value of the ICCGVHD score\&nbsp;=\&nbsp;6). The positive predictive value was 77.1\% (95\% CI: 71.1\%-82.1\%), and the negative predictive value was 87.0\% (95\% CI:81.6-92.5\%). For the patients with systemic GVHD (n\&nbsp;=\&nbsp;171), the sensitivity and specificity were 94.2\% and 67.2\%, respectively (ICCGVHD-score cutoff value\&nbsp;=\&nbsp;6). By receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.903 (95\% CI: 0.859-0.948). For patients without systemic GVHD (n\&nbsp;=\&nbsp;62), the sensitivity and specificity were 100\% and 76.7\%, respectively (ICCGVHD-score cutoff value\&nbsp;=\&nbsp;6). The AUC was 0.891 (95\% CI 0.673-1.000). CONCLUSIONS: Good sensitivity, specificity, predictive value and correlation were found between ICCGVHD and NIH2014. ICCGVHD scores >=6 can be useful to diagnose ocular GVHD with or without systemic GVHD for clinical research.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2022.09.002},
	author = {Ogawa, Yoko and Dana, Reza and Kim, Stella and Jain, Sandeep and Rosenblatt, Mark I and Perez, Victor L and Clayton, Janine A and Alves, Monica and Rocha, Eduardo Melani and Amparo, Francisco and Seo, Kyoung Yul and Wang, Yan and Shen, Joanne and Oh, Joo Youn and Vanathi, Murugesan and Nair, Sridevi and Na, Kyung-Sun and Riemens, Anjo and Sippel, Kimberly and Soifer, Matias and Wang, Shudan and Trindade, Marilia and Kim, Mee Kum and Yoon, Chang Ho and Yagi, Ryuichiro and Hiratsuka, Ryo and Ogawa, Mamoru and Shimizu, Eisuke and Sato, Yasunori and Pflugfelder, Stephen and Tsubota, Kazuo}
}
@article {1363166,
	title = {Overexpression of SPARC in human trabecular meshwork increases intraocular pressure and alters extracellular matrix},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {5},
	year = {2013},
	month = {2013 May 07},
	pages = {3309-19},
	abstract = {PURPOSE: Intraocular pressure (IOP) regulation is largely unknown. SPARC-null mice demonstrate a lower IOP resulting from increased outflow. SPARC is a matricellular protein often associated with fibrosis. We hypothesized that SPARC overexpression would alter IOP by affecting extracellular matrix (ECM) synthesis and/or turnover in the trabecular meshwork (TM). METHODS: An adenoviral vector containing human SPARC was used to increase SPARC expression in human TM endothelial cells and perfused human anterior segments using multiplicities of infection (MOIs) 25 or 50. Total RNA from TM was used for quantitative PCR, while protein from cell lysates and conditioned media were used for immunoblot analyses and zymography. After completion of perfusion, the anterior segments were fixed, sectioned, and examined by light and confocal microscopy. RESULTS: SPARC overexpression increased the IOP of perfused human anterior segments. Fibronectin and collagens IV and I protein levels were elevated in both TM cell cultures and within the juxtacanalicular (JCT) region of perfused anterior segments. Collagen VI and laminin protein levels were increased in TM cell cultures but not in perfused anterior segments. The protein levels of pro-MMP-9 decreased while the kinetic inhibitors of metalloproteinases, TIMP-1 and PAI-1 protein levels, increased at MOI 25. At MOI 50, the protein levels of pro-MMP-1, -3, and -9 also decreased while PAI-1 and TIMP-1 and -3 increased. Only MMP-9 activity was decreased on zymography. mRNA levels of the collagens, fibronectin, and laminin were not affected by SPARC overexpression. CONCLUSIONS: SPARC overexpression increases IOP in perfused cadaveric human anterior segments resulting from a qualitative change the JCT ECM. Selective decrease of MMP-9 activity is likely part of the mechanism. SPARC is a regulatory node for IOP.},
	keywords = {Adenoviridae, Adult, Aged, Aged, 80 and over, Cells, Cultured, Collagen Type I, Collagen Type IV, Extracellular Matrix, Extracellular Matrix Proteins, Fibronectins, Fluorescent Antibody Technique, Indirect, Gene Expression Regulation, Genetic Vectors, Humans, Immunoblotting, Intraocular Pressure, Middle Aged, Osteonectin, Real-Time Polymerase Chain Reaction, RNA, Messenger, Trabecular Meshwork, Transfection, Tumor Suppressor Proteins},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-11362},
	author = {Oh, Dong-Jin and Kang, Min Hyung and Ooi, Yen Hoong and Choi, Kyu Ryong and Sage, E Helene and Rhee, Douglas J}
}
@article {1363167,
	title = {The genetics of intraocular pressure},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {301-5},
	abstract = {Glaucoma is a leading cause of irreversible blindness. Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, yet there is little known about the molecular events that regulate IOP. Genetic and genomic studies have helped identify genes that influence IOP and could lead to the identification of biological pathways that serve as targets for novel pressure-modifying therapies. Genetic linkage studies resulted in the identification of several genes that cause Mendelian (autosomal dominant or autosomal recessive) forms of high-pressure glaucoma, including MYOC. PITX2, FOXC1, and CYP1B1. Classical twin studies suggest that IOP is a heritable trait. More recently, genome-wide association studies (GWAS) have shown that common genetic variants in the GAS7 and TMCO1 genomic regions are associated with elevated IOP. TMCO1 has also been associated with primary open-angle glaucoma in patients with advanced disease. A further study identifying additional genes contributing to IOP will be necessary to fully define the underlying genetic architecture of IOP.},
	keywords = {Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP1B1, Cytoskeletal Proteins, Eye Proteins, Forkhead Transcription Factors, Genetic Variation, Genome-Wide Association Study, Glaucoma, Glycoproteins, Homeodomain Proteins, Humans, Intraocular Pressure, Risk Factors, Transcription Factors},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825291},
	author = {Ojha, Pallavi and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1655721,
	title = {Risk Factors Associated With Pterygium Reoperation in the IRIS Registry},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {11},
	year = {2022},
	month = {2022 Nov 01},
	pages = {1138-1141},
	keywords = {Humans, Pterygium, Recurrence, Registries, Reoperation, Risk Factors},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.3868},
	author = {Oke, Isdin and Hall, Nathan and Tobias Elze and Miller, Joan W and Lorch, Alice C and Hunter, David G and Traish, Aisha S and IRIS Registry Analytic Center Consortium}
}
@article {1698406,
	title = {Improving Estimates of the Geographic Distribution of Pediatric Ophthalmologists to Identify Underserved Regions},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {7},
	year = {2023},
	month = {2023 Jul 01},
	pages = {695},
	keywords = {Child, Humans, Ophthalmologists, Ophthalmology},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.1883},
	author = {Oke, Isdin and Wu, Ann Chen and Hunter, David G}
}
@article {1688311,
	title = {Axial length and corneal curvature of normal eyes in the first decade of life},
	journal = {Eur J Ophthalmol},
	volume = {33},
	number = {6},
	year = {2023},
	month = {2023 Nov},
	pages = {2217-2221},
	abstract = {BACKGROUND/AIMS: To establish normative curves for axial length and corneal curvature in the first decade of life. METHODS: This is a cross-sectional study from a single institution in the United States. Children from 0- to 10-years of age with no underlying ocular pathology were prospectively enrolled to obtain ultrasound biometry and hand-held keratometry while under anaesthesia for an unrelated procedure. Older cooperative children had optical biometry obtained in-office. Logarithmic quantile regression models were used to determine the change in axial length and average keratometry as a function of age. RESULTS: Single-eye measurements from 100 children were included. 75\% of children were White and 49\% female. Median axial length ranged from 20.6 mm (IQR, 20.2 to 21.1 mm) at age one year to 23.1 mm (IQR, 22.5 to 23.8 mm) at age ten years. Median average keratometry ranged from 44.1 D (IQR, 42.6 to 45.4 D) at age one year to 43.5 (IQR, 42.2 to 44.0 D) at age ten years. As age increased, there was a significant increase in axial length (0.74 mm per doubling of age; 95\% CI, 0.62 to 0.82 mm), and a non-significant trend towards lower average keratometry (-0.21 D per doubling of age; 95\% CI, -0.62 to 0.08 D). CONCLUSIONS: We provide a set of normative charts for axial length and corneal curvature which may facilitate the identification of eyes outside the normal range and assist in the management of ocular conditions such as glaucoma or cataract.},
	issn = {1724-6016},
	doi = {10.1177/11206721231167643},
	author = {Oke, Isdin and Nihalani, Bharti R and VanderVeen, Deborah K}
}
@article {1593850,
	title = {Machine Learning Applications in Pediatric Ophthalmology},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {210-217},
	abstract = {Purpose : To describe emerging applications of machine learning (ML) in pediatric ophthalmology with an emphasis on the diagnosis and treatment of disorders affecting visual development.  Methods : Literature review of studies applying ML algorithms to problems in pediatric ophthalmology.  Results : At present, the ML literature emphasizes applications in retinopathy of prematurity. However, there are increasing efforts to apply ML techniques in the diagnosis of amblyogenic conditions such as pediatric cataracts, strabismus, and high refractive error.  Conclusions : A greater understanding of the principles governing ML will enable pediatric eye care providers to apply the methodology to unexplored challenges within the subspecialty.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1890151},
	author = {Oke, Isdin and Vanderveen, Deborah}
}
@article {1748426,
	title = {The impact of the COVID-19 pandemic on the surgical volume of pediatric ophthalmology and strabismus fellows},
	journal = {J AAPOS},
	volume = {27},
	number = {5},
	year = {2023},
	month = {2023 Oct},
	pages = {305-307},
	abstract = {This study used data from the annual fellowship survey over 7 academic years (2014-15 to 2020-21) to describe the trends in surgical experience for pediatric ophthalmology and strabismus fellows and to quantify the impact of the COVID-19 pandemic on trainee surgical volume. The overall number of procedures performed by fellows in the primary surgeon role declined during the first academic year impacted by the pandemic but recovered in the second year. There was an increase in the number of intraocular cases performed per year during the 7-year study interval.},
	keywords = {Child, COVID-19, Education, Medical, Graduate, Fellowships and Scholarships, Humans, Ophthalmology, Pandemics, Surveys and Questionnaires},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.06.006},
	author = {Oke, Isdin and Hunter, David G and Mantagos, Iason S and Heidary, Gena}
}
@article {1653608,
	title = {A decline in the strabismus surgical experience of ophthalmology residents in the United States from 2010 to 2019},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Sep 13},
	abstract = {Subspecialty exposure during residency can influence the future pursuit of fellowship training. In this study, we compared the trends in strabismus surgical experience reported by graduating ophthalmology residents in the United States with other categories of ophthalmic surgery. Over the 10-year period (2010-2019), there was a decline in the total number of strabismus procedures performed during residency by ophthalmology residents graduating in a given year (1.4 fewer cases per year; 95\% CI, 1.1-1.6 [P \&lt; 0.001]). Although several surgical categories experienced a decrease in cases performed in the assistant role, strabismus surgery was the only category with a decrease in cases performed in the surgeon role (0.4 fewer cases per year; 95\% CI, 0.3-0.5 [P \&lt; 0.001]).},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.07.006},
	author = {Oke, Isdin and Heidary, Gena and Mantagos, Iason S and Shah, Ankoor S and Hunter, David G}
}
@article {1698391,
	title = {Use and Costs of Instrument-Based Vision Screening for US Children Aged 12 to 36 Months},
	journal = {JAMA Pediatr},
	year = {2023},
	month = {2023 May 22},
	issn = {2168-6211},
	doi = {10.1001/jamapediatrics.2023.0808},
	author = {Oke, Isdin and Lutz, Sharon M and Hunter, David G and Galbraith, Alison A}
}
@article {1782301,
	title = {Surgical Approach and Reoperation Risk in Intermittent Exotropia in the IRIS Registry},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {1},
	year = {2024},
	month = {2024 Jan 01},
	pages = {48-52},
	abstract = {IMPORTANCE: There is no consensus on the optimal surgical treatment for children with intermittent exotropia (IXT).

OBJECTIVE: To compare the 5-year reoperation rates for children with IXT treated with horizontal muscle strabismus surgery using bilateral lateral rectus recession (BLR) vs unilateral lateral rectus recession with medial rectus resection (RR).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined data obtained from the Intelligent Research in Sight (IRIS) Registry on 7482 children (age, \&lt;18 years) with IXT who underwent horizontal eye muscle strabismus surgery between January 1, 2013, and December 31, 2017. Children undergoing initial surgeries involving 3 or more horizontal muscles, vertical muscles, or reoperations were excluded.

MAIN OUTCOMES AND MEASURES: The primary outcome was the adjusted cumulative incidence of repeat horizontal muscle surgery within 5 years after the initial surgery. Reoperation risk was analyzed using adjusted hazard ratios (AHRs) derived from multivariable Cox regression models, adjusting for individual demographic and surgical factors (age, sex, race and ethnicity, US Census region, and surgeon subspecialty). Data were analyzed between January 16 and September 20, 2023.

RESULTS: The study included 7482 children (median [IQR] age at initial surgery, 6 [4-9] years; 3945 females [53\%]) with IXT treated with horizontal muscle strabismus surgery. Bilateral lateral rectus recession was performed more frequently than RR (85.3\% vs 14.7\%, P \&lt; .001), especially in younger children (rates of BLR vs RR by age: age 0 to <=4 years, 88.4\% vs 11.6\%; age 5 to <=11 years, 84.7\% vs 15.3\%; age 12 to <=17 years, 78.1\% vs 21.9\%; P \&lt; 0.001). After data adjustment, the 5-year cumulative incidence of reoperation was 21.3\% (95\% CI, 20.1\%-22.5\%). The adjusted 5-year cumulative incidence of reoperation was higher for BLR than for RR (22.2\% vs 17.2\%; difference, 4.9\%; 95\% CI, 1.9\%-8.0\%). Unilateral lateral rectus recession with medial rectus resection was associated with a lower 5-year reoperation risk compared with BLR (AHR, 0.77; 95\% CI, 0.64-0.93). Younger age at time of initial surgery was associated with a higher reoperation risk (AHR per 1-year decrease, 1.09; 95\% CI, 1.07-1.11) after adjusting for all other covariates.

CONCLUSIONS AND RELEVANCE: In this nationwide registry, approximately 1 in 5 children with IXT underwent reoperation within 5 years after the initial surgery. Children treated with RR were less likely to require a reoperation within 5 years compared with those treated with BLR. Further efforts to identify modifiable risk factors for reoperation are needed to reduce the surgical burden and improve outcomes for children with IXT.},
	keywords = {Adolescent, Child, Child, Preschool, Chronic Disease, Cohort Studies, Exotropia, Female, Follow-Up Studies, Humans, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Registries, Reoperation, Retrospective Studies, Treatment Outcome, Vision, Binocular},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.5288},
	author = {Oke, Isdin and Tobias Elze and Miller, Joan W and Lorch, Alice C and Hunter, David G}
}
@article {1677831,
	title = {Comment on: "Evaluation of Systemic Medications Associated With Surgically Treated Cataract Among US Adults"},
	journal = {Am J Ophthalmol},
	volume = {251},
	year = {2023},
	month = {2023 Jul},
	pages = {199},
	keywords = {Adult, Cataract, Cataract Extraction, Humans},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.01.030},
	author = {Oke, Isdin and Boland, Michael V}
}
@article {1642029,
	title = {The accuracy of intraocular lens calculation varies by age in the Infant Aphakia Treatment Study},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 May 06},
	abstract = {Refraction predictions from intraocular lens (IOL) calculation formulae are inaccurate in children. We sought to quantify the relationship between age and prediction error using a model derived from the biometry measurements of children enrolled in the Infant Aphakia Treatment Study (IATS) when they were <=7 months of age. We calculated theoretical predicted refractions in diopters (D) using axial length, average keratometry, and IOL powers at each measurement time point using the Holladay 1 formula. We compared the predicted refraction to the actual refraction and calculated the absolute prediction error (APE). We found that the median APE was 1.60 D (IQR, 0.73-3.11 D) at a mean age (corrected for estimated gestational age) of 0.20 {\textpm} 0.14 years and decreased to 1.11 D (IQR, 0.42-2.20 D) at 10.60 {\textpm} 0.27 years. We analyzed the association of age with APE using linear mixed-effects models adjusting for axial length, average keratometry, and IOL power and found that as age doubled, APE decreased by 0.25 D (95\% CI, 0.09-0.40 D). The accuracy of IOL calculations increases with age, independent of biometry measurements and IOL power.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.02.004},
	author = {Oke, Isdin and VanderVeen, Deborah K and McClatchey, Thaddeus S and Lambert, Scott R and McClatchey, Scott K and Infant Aphakia Treatment Study Group}
}
@article {1653586,
	title = {Periodic Trends in Internet Searches for Ocular Symptoms in the US},
	journal = {Ophthalmic Epidemiol},
	volume = {30},
	number = {4},
	year = {2023},
	month = {2023 Aug},
	pages = {352-357},
	abstract = {PURPOSE: To identify periodic trends in internet searches for ocular symptoms and to determine the seasonal peaks and troughs. METHODS: This cross-sectional study examined publicly available Google Trends data from the United States (01/01/2015 to 12/31/2019). A list of common ocular symptoms was compiled from the American Academy of Ophthalmology Eye Health website and Wills Eye Manual. Ocular symptoms were stratified into categories involving vision change, eye pain, or eye redness. The search volume over time for each term was modeled using periodic regression functions and the goodness-of-fit was reported. Fisher{\textquoteright}s exact tests were used to compare the characteristics of periodic vs. non-periodic query terms. RESULTS: Seasonal trends were demonstrated by 45\% (48/106) of the ocular symptoms included in this investigation. Search terms with best fit to the periodic model included stye (r2\&nbsp;=\&nbsp;0.89), pink eye (r2\&nbsp;=\&nbsp;0.82), dry eye (r2\&nbsp;=\&nbsp;0.76), blurry vision (r2\&nbsp;=\&nbsp;0.72), and swollen eye (r2\&nbsp;=\&nbsp;0.71). Periodic search terms were more likely to involve eye redness (21\% vs. 11\%, p =\&nbsp;.014) and less likely to involve vision change (11\% vs. 36\%; p \&lt;\&nbsp;.001). Periodic queries involving eye redness most often peaked in the spring and those involving eye pain peaked in the summer. CONCLUSION: Ocular symptom queries directly reflect seasonal trends for allergic eye disease and ocular trauma. Search query analyses can serve as accurate epidemiological tools with research and real-world clinical applications.},
	keywords = {Cross-Sectional Studies, Eye Diseases, Eye Pain, Humans, Internet, Ophthalmology, United States},
	issn = {1744-5086},
	doi = {10.1080/09286586.2022.2119260},
	author = {Oke, Isdin and Gaier, Eric D and Mantagos, Iason S and Shah, Ankoor S}
}
@article {1798501,
	title = {Gaps in the Vision Screening Pathway for School-Aged US Children},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {268-270},
	keywords = {Child, Humans, Schools, Students, Vision Screening},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.6316},
	author = {Oke, Isdin and Slopen, Natalie and Galbraith, Alison A and Hunter, David G and Wu, Ann Chen}
}
@article {1748461,
	title = {Factors associated with visual acuity improvement with a binocular digital therapeutic for amblyopia},
	journal = {J AAPOS},
	volume = {27},
	number = {5},
	year = {2023},
	month = {2023 Oct},
	pages = {300-303},
	abstract = {We combined data from 121 amblyopic children enrolled in two prospective open-label pilot studies and a randomized trial of a binocular digital therapeutic to identify factors associated with positive response to amblyopia treatment. Visual acuity improved >=1 line in 81\% of participants after 12 weeks of therapy. Treatment response was not found to be associated with age, severity of amblyopia, or prior treatment status. Although these findings may suggest broad efficacy for this treatment approach, further investigation in larger cohorts is needed to identify factors associated with treatment response.},
	keywords = {Amblyopia, Child, Child, Preschool, Follow-Up Studies, Humans, Prospective Studies, Treatment Outcome, Video Games, Vision, Binocular, Visual Acuity},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.06.007},
	author = {Oke, Isdin and Gaier, Eric D and Repka, Michael X}
}
@article {1782341,
	title = {Aberrant regeneration in an international registry of patients with 3rd-nerve palsy},
	journal = {Eur J Ophthalmol},
	volume = {33},
	number = {6},
	year = {2023},
	month = {2023 Nov},
	pages = {2154-2161},
	abstract = {BACKGROUND/AIMS: To describe the patterns of pre-operative aberrant regeneration and motility outcomes reported in an international registry of patients with 3rd-nerve palsy treated with nasal transposition of the split lateral rectus muscle (NTSLR). METHODS: This cross-sectional study used data from an international, multicentre registry of patients with 3rd-nerve palsy treated with NTSLR. Patients with aberrant regeneration were identified, and patterns of innervation described. Demographics and postoperative success defined as horizontal alignment <=15 PD were compared based on the presence, and type, of aberrant regeneration using Wilcoxon rank sum and Fisher{\textquoteright}s exact tests. RESULTS: Aberrant regeneration was reported in 16\% (21/129) of patients. Age at diagnosis, sex, and aetiology of palsy were not significantly associated with aberrant regeneration. Abnormal movements were triggered by adduction in 52\% (11/21), infraduction in 23\% (5/21), and supraduction in 23\% (5/21) of cases. Presentation patterns involved rectus muscle innervation in 29\% (6/21) and levator muscle innervation in 71\% (15/21) of cases. Although patients with aberrant regeneration had similar probability of success in comparison to those without following NTLSR (76\% vs. 69\%, p = 0.5), those with abnormal innervation of a rectus muscle had a lower success rate than those with abnormal innervation of the levator palpebrae superioris muscle (17\% vs. 93\%; p = 0.002). CONCLUSION: Successful treatment of a 3rd nerve palsy with NTSLR was not influenced by aberrant regeneration involving the levator muscle. Alternative surgical interventions should be considered when aberrant regeneration alters rectus muscle function given its adverse impact on motor outcomes with NTSLR.},
	issn = {1724-6016},
	doi = {10.1177/11206721231161377},
	author = {Oke, Isdin and Lorenz, Birgit and Basiakos, Sotirios and Gokyigit, Birsen and Laurent, Erick and Tsai, Chong-Bin and Orge, Faruk and Heidary, Gena and Tjeerd de Faber, Jan and Jeddawi, Laila and Sadiq, Mohammad Ali and Strominger, Mitchell and Ugo Dodd, Mary-Magdalene and Shah, Ankoor S and Dagi, Linda R and NTSLR3NP Study Group}
}
@article {1638575,
	title = {Comparison of fellowship match opportunities and results across pediatric surgical subspecialities},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Apr 23},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.02.005},
	author = {Oke, Isdin and Heidary, Gena and Mantagos, Iason S and Shah, Ankoor S and Hunter, David G}
}
@article {1761911,
	title = {Vision Screening Among Children With Private Insurance: 2010-2019},
	journal = {Pediatrics},
	volume = {152},
	number = {3},
	year = {2023},
	month = {2023 Sep 01},
	abstract = {OBJECTIVES: To describe trends in vision screening based on insurance claims for young children in the United States. METHODS: This cross-sectional study used administrative claims data from the 2010-2019 IBM MarketScan Commercial Claims and Encounters Database. We included children aged 1 to \&lt;5 years at the beginning of each calendar year. The primary outcome was a vision screening claim within 12 months for chart-based or instrument-based screening. Linear regression was used to evaluate trends over time in vision screening claims and practitioner payment. RESULTS: This study included a median of 810 048 (interquartile range, 631 523 - 1 029 481) children between 2010 and 2019 (mean [standard deviation] age, 2.5 [1.1] years; 48.7\% female). The percentage of children with vision screening claims increased from 16.7\% in 2010 to 44.3\% in 2019 (difference, 27.5\%; 95\% confidence interval, 27.4\% to 27.7\%). Instrument-based screening claims, which were identified in \&lt;0.2\% of children in 2010, increased to 23.4\% of children 1 to \&lt;3 years old and 14.4\% of children 3 to \&lt;5 years old by 2019. From 2013 to 2018, the average of the median practitioner payment for instrument-based screening was $23.70, decreasing $2.10 per year during this time (95\% confidence interval, $0.85 to $3.34; P = .009). CONCLUSIONS: Vision screening claims among young children nearly tripled over the last decade, and this change was driven by increased instrument-based screening for children aged \&lt;3 years. Further investigation is needed to determine whether the decreasing trends in practitioner payment for screening devices will reduce the adoption of vision screening technology in clinical practice.},
	keywords = {Child, Child, Preschool, Cross-Sectional Studies, Databases, Factual, Female, Humans, Insurance, Linear Models, Male, Vision Screening},
	issn = {1098-4275},
	doi = {10.1542/peds.2023-062114},
	author = {Oke, Isdin and Lutz, Sharon M and Hunter, David G and Galbraith, Alison A}
}
@article {1773476,
	title = {Vision Testing for Adolescents in the US},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {11},
	year = {2023},
	month = {2023 Nov 01},
	pages = {1068-1072},
	abstract = {IMPORTANCE: Untreated refractive error contributes to the racial, ethnic, and socioeconomic disparities in visual function of adolescent children in the US. OBJECTIVE: To describe patterns in vision testing as a function of age among US adolescents and identify sociodemographic factors associated with vision testing. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the National Survey of Children{\textquoteright}s Health (2018-2019), a nationally representative survey of the noninstitutionalized US pediatric population. A total of 24 752 adolescent children (aged 12 to \&lt;18 years) were included. Data were analyzed from March 22 to August 11, 2023. MAIN OUTCOMES AND MEASURES: The primary outcome was the caregiver report of vision testing within the last 12 months. Linear regression was used to describe the patterns in reported vision testing as a function of participant age. Logistic regression was used to describe the association of sociodemographic factors with the report of vision testing in each setting. RESULTS: Among 24 752 adolescents, the median (IQR) age was 14 (13-16) years; 12 918 (weighted, 51\%) were male. Vision testing in any setting within the previous year was reported by caregivers of 18 621 adolescents (weighted, 74\%). Vision testing was reported to have occurred at an eye clinic in 13 323 participants (weighted, 51\%), at a primary care clinic in 5230 participants (weighted, 22\%), at a school in 2594 participants (weighted, 11\%), and at a health center in 635 participants (weighted, 4\%). The percentage of adolescents reported to have vision tested decreased with age (-1.3\% per year; 95\% CI, -2.5\% to 0\% per year) due to a decrease in testing in primary care and school settings. After adjusting for age and sex, there were lower odds of vision testing reported for adolescents who were uninsured vs insured (adjusted odds ratio [AOR], 0.81; 95\% CI, 0.76-0.87), had caregivers with less than vs greater than high school education (AOR, 0.89; 95\% CI, 0.84-0.95), and were from a family born outside vs inside the US (AOR, 0.90; 95\% CI, 0.82-0.98). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, vision testing in adolescents decreased as a function of age due to fewer reported tests performed in primary care and school-based settings. Relative to children in socioeconomically advantaged families, those from disadvantaged families were less likely to report receiving vision testing in clinical settings. Efforts to expand the role of school-based vision testing for older adolescents from disadvantaged backgrounds may enable opportunities to address disparities in untreated refractive error.},
	keywords = {Adolescent, Child, Cross-Sectional Studies, Female, Humans, Male, Refractive Errors, Surveys and Questionnaires, Vision Tests, Vision, Low},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.4475},
	author = {Oke, Isdin and Slopen, Natalie and Hunter, David G and Wu, Ann Chen}
}
@article {1645484,
	title = {Nasal Transposition of the Split Lateral Rectus Muscle for Strabismus Associated With Bilateral 3rd-Nerve Palsy},
	journal = {Am J Ophthalmol},
	volume = {242},
	year = {2022},
	month = {2022 Oct},
	pages = {165-172},
	abstract = {PURPOSE: To determine the success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating bilateral 3rd-nerve palsy. DESIGN: Retrospective, interventional case series. METHODS: An international, multicenter registry was used for the study. The study population was all patients with bilateral 3rd-nerve palsy treated with NTSLR. Sensorimotor evaluations were conducted before and 6 months after unilateral or bilateral NTSLR. Outcome measures were postoperative horizontal alignment <=15 prism diopters (PD), intraoperative technical difficulties, and vision-threatening complications. The association of patient demographics and surgical technique with each outcome was analyzed using multivariable logistic regression. RESULTS: A total of 34 patients were included, with a median age of 46 years (interquartile range [IQR]\&nbsp;=\&nbsp;25-54 years) at surgery. The most common etiologies were ischemic (29\%), neoplastic (15\%), and congenital (12\%). NTSLR performed unilaterally with alternative surgery on the opposite eye (65\%) resulted in a median postoperative exotropia of 18 PD (IQR\&nbsp;=\&nbsp;7-35 PD), and when performed bilaterally (35\%) resulted in postoperative exotropia of 14 PD (IQR\&nbsp;=\&nbsp;5-35 PD). Success was achieved in 50\% of cases, intraoperative technical difficulties were reported in 18\%, and vision-threatening complications occurred in 21\%. Attachment of the lateral rectus muscle >=10 mm posterior to the medial rectus insertion was associated with increased vision-threatening complications (odds ratio\&nbsp;=\&nbsp;9.0; 95\% CI\&nbsp;=\&nbsp;1.3-99). CONCLUSIONS: NTSLR can address the large-angle exotropia associated with bilateral 3rd-nerve palsy. Surgeons should be aware that posterior placement of the lateral rectus muscle may increase the risk of vision-threatening complications, particularly serous choroidal effusion.},
	keywords = {Adult, Exotropia, Follow-Up Studies, Humans, Middle Aged, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Paralysis, Retrospective Studies, Strabismus, Treatment Outcome, Vision, Binocular},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.06.010},
	author = {Oke, Isdin and Lorenz, Birgit and Basiakos, Sotirios and Gokyigit, Birsen and Ugo Dodd, Mary-Magdalene and Laurent, Erick and Hunter, David G and Goberville, Mitra and Elkamshoushy, Amr and Tsai, Chong-Bin and Orge, Faruk and Velez, Federico G and Jeddawi, Laila and Gravier, Nicholas and Li, Ningdong and Shah, Ankoor S and Dagi, Linda R and NTSLR3NP Study Group}
}
@article {1655732,
	title = {Systemic Barriers in Receiving Electronically Prescribed Glaucoma Medications},
	journal = {J Glaucoma},
	volume = {31},
	number = {10},
	year = {2022},
	month = {2022 10 01},
	pages = {812-815},
	abstract = {PRCIS: Over a third of electronically prescribed glaucoma medications were not picked up within 1 month of patient request. Feedback-driven protocols may help minimize treatment interruptions attributed to electronic prescribing. PURPOSE: Glaucoma treatment relies on long-term medication compliance and many socioeconomic factors impact the ability of patients to receive their medications. This study aims to quantify treatment interruptions attributable to electronically prescribed medications and propose interventions to minimize this barrier. METHODS: This is a cross-sectional study of the electronic prescribing patterns at a tertiary care hospital serving a socioeconomically diverse patient population. Glaucoma medication refill requests received over a 6-week interval were reviewed and patient pharmacies were contacted 1 month after the request date to determine whether the medication was received by the patient. Patients who did not pick up the prescriptions were contacted and consented to participate in a survey to identify the barriers to acquiring the medications. RESULTS: Refill requests of 198 glaucoma medications met the inclusion criteria and the most common classes were prostaglandin analogs (44\%) and alpha-2-agonists (21\%). Medications were not obtained within 1 month in 71 (35.9\%) cases. Prior authorization requirement was significantly associated with patients not obtaining their medication (odds ratio, 0.07; 95\% confidence interval, 0.03-0.45). Patient reported challenges to successful receipt electronically prescribed medications included insurance coverage (32.2\%) and pharmacy availability (22.6\%). CONCLUSIONS: Approximately a third of electronically prescribed glaucoma medications were not received by patients within a month of refill request due to the need for prior authorization, insurance coverage, and pharmacy availability. A mechanism to alert providers and to address these barriers to medication access may minimize treatment interruption and disease progression.},
	keywords = {Cross-Sectional Studies, Glaucoma, Humans, Intraocular Pressure, Medication Adherence, Surveys and Questionnaires},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002100},
	author = {Oke, Isdin and Badami, Avni and Kosteva, Kathryn L and Wu, Kevin and Desai, Manishi A}
}
@article {1642017,
	title = {Advanced retinoblastoma presenting with cataract in a child with limited access to primary care},
	journal = {J Pediatr},
	year = {2022},
	month = {2022 May 13},
	issn = {1097-6833},
	doi = {10.1016/j.jpeds.2022.05.019},
	author = {Oke, Isdin and Diller, Lisa R and Gonzalez, Efren}
}
@article {1732706,
	title = {Gaze-Evoked Vision Changes},
	journal = {J Binocul Vis Ocul Motil},
	volume = {73},
	number = {3},
	year = {2023},
	month = {2023 Jul 03},
	pages = {75-76},
	abstract = {We describe an atypical presentation of aberrant regeneration of the 3rd cranial nerve causing vision changes with ocular motility. Abnormal communication between axons destined for the medial rectus and those destined for muscles involved in the accommodative response resulted in simultaneous pupil constriction and myopic shift of approximately 2.5 diopters with adduction. While there have been several reports of this pupillary response (Czarnecki sign), no cases have documented the change in refraction from ciliary muscle involvement.},
	keywords = {Eye Movements, Humans, Myopia, Oculomotor Muscles, Refraction, Ocular, Vision Tests},
	issn = {2576-1218},
	author = {Oke, Isdin and Ness, Steven D and Peeler, Crandall E}
}
@article {1653590,
	title = {Adjustable Suture Technique Is Associated with Fewer Strabismus Reoperations in the Intelligent Research in Sight Registry},
	journal = {Ophthalmology},
	volume = {129},
	number = {9},
	year = {2022},
	month = {2022 09},
	pages = {1028-1033},
	abstract = {PURPOSE: To compare the reoperation rates after strabismus surgery with and without the adjustable suture technique. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or older in the Intelligent Research in Sight (IRIS{\textregistered}) Registry who underwent strabismus surgery between January 1, 2013, and December 31,\&nbsp;2018. METHODS: Data were collected from the electronic health records of practices participating in the IRIS Registry. The primary exposure of interest was use of the adjustable suture technique, identified by Current Procedural Terminology coding. MAIN OUTCOME MEASURES: The primary outcome was repeat strabismus surgery within 1 year of initial strabismus surgery. Odds ratios (ORs) were derived from a multivariable logistic regression model evaluating the association between the use of adjustable sutures and reoperation rate, adjusting for patient demographics and surgical factors. RESULTS: A total of 34 872 patients who underwent strabismus surgery during the study interval were identified: 72\% underwent horizontal muscle surgery, 17\% underwent vertical muscle surgery, and 11\% underwent combined horizontal and vertical muscle surgery. Adjustable sutures were used in 18\% of patients. The overall reoperation rate within 1 year of strabismus surgery was 7.7\%. The 1-year reoperation rate was 6.0\% for patients treated with adjustable sutures and 8.1\% for patients treated without adjustable sutures (P \&lt; 0.001). The multivariable regression model revealed a statistically significant 30\% decrease in the odds of reoperation within 1 year of surgery when adjustable sutures were used (OR, 0.70; 95\% confidence interval [CI], 0.62-0.78), a 40\% increase in those with a history of prior strabismus surgery (OR, 1.40; 95\% CI, 1.28-1.53), and a 9\% increase per decade of age at surgery (OR, 1.09; 95\% CI, 1.06-1.11). CONCLUSIONS: In adults cared for in practices participating in the IRIS Registry, the adjustable suture technique was associated with a significantly lower reoperation rate within 1 year of undergoing horizontal or combined horizontal and vertical strabismus surgery. Adjustable suture use in vertical strabismus surgery alone did not reduce the 1-year reoperation rate significantly. A history of prior strabismus surgery was associated with increased odds of reoperation.},
	keywords = {Adolescent, Adult, Humans, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Registries, Reoperation, Retrospective Studies, Strabismus, Suture Techniques},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.04.021},
	author = {Oke, Isdin and Hall, Nathan and Tobias Elze and Miller, Joan W and Lorch, Alice C and Hunter, David G and IRIS Data Analytics Committees}
}
@article {1603857,
	title = {Botulinum Toxin Injection of the Inferior Oblique Muscles for V-Pattern Strabismus and Primary Position Hypertropia},
	journal = {Am J Ophthalmol},
	volume = {235},
	year = {2022},
	month = {2022 Mar},
	pages = {32-37},
	abstract = {PURPOSE: To evaluate outcomes of botulinum toxin (BTX) injection of the inferior oblique (IO) muscle. DESIGN: Retrospective case series. METHODS: Setting: Single center, ophthalmology department at Boston Children{\textquoteright}s Hospital. STUDY POPULATION: All patients treated with IO muscle injection of BTX (onabotulinumtoxinA) between 2010 and 2020. OBSERVATION PROCEDURE: Sensorimotor evaluations at short-term (\&lt;2 months), medium-term (2-4 months), and long-term (>=4 months) intervals. OUTCOME MEASURE: Primary outcomes included median improvement in V-pattern strabismus and primary position hypertropia. Secondary outcomes included IO muscle overaction. Wilcoxon signed-rank tests were performed to identify differences before and after injection. RESULTS: Record review identified 20 patients with a median age of 4.5 (range, 1-69) years. Median BTX dose injected (31 IO muscles) was 5.0 (range, 3.0-7.0) units. Indications included V-pattern strabismus (N\&nbsp;=\&nbsp;8), hypertropia (N\&nbsp;=\&nbsp;7), or both (N\&nbsp;=\&nbsp;5). Median long-term interval was 6.4 (range, 4.1-26.6) months. Injections were concurrent with treatment of horizontal strabismus in all but 3 cases. Median V-pattern magnitude changed from 10 prism diopters (PD) preoperatively to 0 PD short-term (P\&nbsp;=\&nbsp;.006) and 3.5 PD long-term (P\&nbsp;=\&nbsp;.34). Median hypertropia changed from 8.5 PD preoperatively to 1.5 PD short-term (P\&nbsp;=\&nbsp;.01) and 8 PD long-term (P\&nbsp;=\&nbsp;.87). Median IO muscle overaction grade improved significantly at short-term (P \&lt; .001) and long-term (P\&nbsp;=\&nbsp;.007) intervals. There were no complications associated with the IO muscle injections. CONCLUSIONS: BTX injection of the IO muscles can be a useful adjunct to the management of V-pattern strabismus. Intervention for primary position hypertropia may be helpful for short-term relief with no expectation of long-term benefit.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.07.003},
	author = {Oke, Isdin and Elhusseiny, Abdelrahman M and Shah, Ankoor S and Hunter, David G}
}
@article {1658688,
	title = {Extraocular muscle ductions following nasal transposition of the split lateral rectus muscle},
	journal = {Can J Ophthalmol},
	volume = {58},
	number = {6},
	year = {2023},
	month = {2023 Dec},
	pages = {565-569},
	abstract = {OBJECTIVE: To quantify changes in ductions following nasal transposition of the split lateral rectus muscle (NTSLR) for treating third nerve palsy. DESIGN: Retrospective cohort study. PARTICIPANTS: A single eye from each patient with third nerve palsy treated with NTSLR with ocular motility measurements. METHODS: Observation of changes in pre- and postoperative ductions. Outcome measures including patient demographic and surgical factors associated with the ability to adduct beyond the midline after NTSLR were evaluated using multivariable logistic regression. RESULTS: A total of 116 patients met the inclusion criteria for this study. The NTSLR significantly decreased abduction (median of 0 limitation [interquartile range (IQR), 0-0] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p \&lt; 0.001), with a corresponding improvement in adduction (median, -5 [IQR, -5 to -4] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p \&lt; 0.001). There was no change in median supraduction or infraduction after NTSLR (p \&gt; 0.05). The ability to adduct beyond the midline after NTSLR was demonstrated in 42\% of patients. Although not statistically significant, a trend toward a postoperative ability to adduct beyond the midline was seen in patients who had concurrent superior oblique muscle tenotomy (odds ratio [OR] = 5.08; 95\% CI, 0.91-40.9) or who were designated with partial rather than complete third nerve palsy (OR = 2.29; 95\% CI, 0.82-6.70). CONCLUSIONS: NTSLR improves the horizontal midline positioning of eyes with third nerve palsy. Most eyes lose the ability to abduct, but some regain a modest ability to adduct while vertical ductions remain unchanged.},
	keywords = {Eye Movements, Humans, Nose, Oculomotor Muscles, Oculomotor Nerve Diseases, Ophthalmologic Surgical Procedures, Retrospective Studies, Strabismus},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2022.10.019},
	author = {Oke, Isdin and Lorenz, Birgit and Basiakos, Sotirios and Gokyigit, Birsen and Ugo Dodd, Mary-Magdalene and Laurent, Erick and Sadiq, Mohammad Ali and Goberville, Mitra and Elkamshoushy, Amr and Tsai, Chong-Bin and Gravier, Nicholas and Speeg-Schatz, Claude and Shepherd, James Banks and Saxena, Rohit and Soni, Ajay and Hunter, David G and Shah, Ankoor S and Dagi, Linda R and NTSLR3NP Study Group}
}
@article {1615219,
	title = {Rates of unverifiable and incomplete publications in pediatric ophthalmology fellowship applicants},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Sep 25},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2021.04.013},
	author = {Oke, Isdin and Mantagos, Iason S}
}
@article {1798491,
	title = {Factors associated with the use of botulinum toxin injections for adult strabismus in the IRIS Registry},
	journal = {J AAPOS},
	volume = {28},
	number = {1},
	year = {2024},
	month = {2024 Feb},
	pages = {103817},
	abstract = {This cross-sectional study used data from a large nationwide registry to describe the factors associated with use of botulinum toxin injections for adults with strabismus in the United States. Botulinum toxin injections were performed on 3.1\% of adults undergoing an intervention for strabismus between 2013 and 2020. Adults treated with botulinum toxin injections were more likely to be older and female. Compared to non-Hispanic White patients, non-Hispanic Black patients were three times less likely to receive treatment with botulinum toxin after adjusting for age, sex, geographic region, and type of insurance. Efforts to understand the factors contributing to disparities in the use of botulinum toxin for strabismus may lead to opportunities for more equitable access to this intervention.},
	keywords = {Adult, Botulinum Toxins, Type A, Cross-Sectional Studies, ethnicity, Female, Humans, Oculomotor Muscles, Strabismus},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.09.011},
	author = {Oke, Isdin and Tobias Elze and Miller, Joan W and Lorch, Alice C and Hunter, David G}
}
@article {1638566,
	title = {Chorioretinal Scars From Scleral Perforation During Prior Strabismus Surgery},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {4},
	year = {2022},
	month = {2022 Apr 01},
	pages = {e215711},
	keywords = {Cicatrix, Humans, Oculomotor Muscles, Sclera, Scleral Buckling, Strabismus},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.5711},
	author = {Oke, Isdin and Hunter, David G}
}
@article {1661842,
	title = {The contribution of intraocular lens calculation accuracy to the refractive error predicted at 10 years in the Infant Aphakia Treatment Study},
	journal = {J AAPOS},
	volume = {26},
	number = {6},
	year = {2022},
	month = {2022 Dec},
	pages = {294.e1-294.e5},
	abstract = {PURPOSE: To determine the relative contribution of intraocular lens (IOL) calculation accuracy and ocular growth variability to the long-term refractive error predicted following pediatric cataract surgery. METHODS: Pseudophakic eyes of children enrolled in the Infant Aphakia Treatment Study (IATS) were included in this study. Initial absolute prediction error (APE) and 10-year APE were calculated using the initial biometry, IOL parameters, postoperative refractions, and mean rate of refractive growth. The cohort was divided into children with a low-initial APE (<=1.0 D) and a high-initial APE ( \&gt;1.0 D). The 10-year APE was compared between the two groups using the Mann-Whitney U test. Linear regression was used to estimate the variability in prediction error explained by the initial IOL calculation accuracy. RESULTS: Forty-two children with IOL placement in infancy were included. Seventeen eyes had a low initial APE, and 25 eyes had a high initial APE. There was no significant difference in APE 10 years following surgery between individuals with a low initial APE (median, 2.67 D; IQR, 1.61-4.12 D) and a high initial APE (median, 3.45 D; IQR, 1.64-5.10 D) (P = 0.7). Initial prediction error could explain 12\% of the variability in the prediction error 10 years following surgery. CONCLUSIONS: IOL calculation accuracy contributed minimally to the refractive error predicted 10 years after cataract surgery in the setting of high variability in the rate of refractive growth.},
	keywords = {Animals, Aphakia, Biometry, Cataract, Child, Hominidae, Humans, Infant, Lens Implantation, Intraocular, Lenses, Intraocular, Refraction, Ocular, Refractive Errors, Retrospective Studies, Visual Acuity},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.09.008},
	author = {Oke, Isdin and VanderVeen, Deborah K and McClatchey, Thaddeus S and Lambert, Scott R and McClatchey, Scott K and Infant Aphakia Treatment Study Group}
}
@article {1664981,
	title = {Smoking Is Associated With a Higher Risk of Surgical Intervention for Thyroid Eye Disease in the IRIS Registry},
	journal = {Am J Ophthalmol},
	volume = {249},
	year = {2023},
	month = {2023 May},
	pages = {174-182},
	abstract = {PURPOSE: To describe the association of smoking status with surgical intervention for thyroid eye disease (TED) at the population-level. DESIGN: Retrospective cohort study. METHODS: This study included all adults (aged >=18 years) with Graves disease in the Intelligent Research in Sight (IRIS) Registry (January 1, 2013, to December 31, 2020). The primary outcome was surgical intervention for TED, stratified into orbital decompression, strabismus surgery, and eyelid recession surgery. The Kaplan-Meier estimated 5-year cumulative probability for each surgical intervention was calculated. Multivariable Cox regression was used to evaluate the association between smoking status and each surgical intervention, adjusting for age, sex, race, ethnicity, and geographic region. RESULTS: This study included 87,774 patients. Median age was 59 years (IQR, 48-68 years); 81\% were female patients. Current smokers had a greater 5-year cumulative probability of orbital decompression (3.7\% vs 1.9\%; P \&lt; .001), strabismus surgery (4.6\% vs 2.2\%; P \&lt; .001), and eyelid recession (4.1\% vs 2.6\%; P \&lt; .001) compared to never smokers. After adjusting for demographic factors, current smokers were at greater risk for orbital decompression (hazard ratio [HR], 2.1; 95\% CI, 1.8-2.4; P \&lt; .001), strabismus surgery (HR, 2.0; 95\% CI, 1.8-2.3; P \&lt; .001), and eyelid recession (HR, 1.7; 95\% CI, 1.5-1.9; P \&lt; .001) than never smokers. Former smokers were at higher risk for each type of surgery for TED, albeit at lower levels than current smokers. CONCLUSIONS: Smoking was associated with increased risk of surgical intervention for TED in the IRIS Registry. Former smokers were at a lower risk than current smokers, supporting the role of smoking cessation on lowering the burden of surgical disease at the population-level.},
	keywords = {Adolescent, Adult, Decompression, Surgical, Female, Graves Ophthalmopathy, Humans, Male, Middle Aged, Retrospective Studies, Smoking, Strabismus},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.01.020},
	author = {Oke, Isdin and Reshef, Edith R and Tobias Elze and Miller, Joan W and Lorch, Alice C and Hunter, David G and Freitag, Suzanne K and IRIS Registry Analytic Center Consortium}
}
@article {1806581,
	title = {The Incidence of Strabismus After Upper and Lower Blepharoplasty in the United States},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2024},
	month = {2024 Feb 09},
	abstract = {PURPOSE: To compare the incidence of strabismus after upper and lower blepharoplasty in the United States. METHODS: Retrospective cohort study of adults (age >=18 years) in the IRIS Registry (Intelligent Research in Sight) who underwent blepharoplasty between January 1, 2013 and December 31, 2020. The primary outcome was the Kaplan-Meier estimated cumulative incidence of strabismus diagnosis and surgery within 3 years of blepharoplasty. Multivariable Cox regression was used to determine the association of blepharoplasty type with strabismus diagnosis and surgery, adjusting for patient age, sex, and geographic region. RESULTS: Blepharoplasty was performed in 368,623 patients (median [interquartile range] age, 69 [63-75] years, and 69\% female). Compared with those undergoing upper eyelid blepharoplasty, patients treated with lower eyelid blepharoplasty were slightly younger (median age, 66 vs. 69 years; p \&lt; 0.001) and more likely to be female (71\% vs. 69\%; p \&lt; 0.001). There was a greater 3-year incidence of strabismus diagnosis (2.0\% vs. 1.5\%; p \&lt; 0.001) and a greater 3-year incidence of strabismus surgery (0.15\% vs. 0.06\%; p = 0.003) for individuals undergoing lower vs. upper blepharoplasty. After adjusting for age, sex, and geographic region, lower blepharoplasty was associated with a higher 3-year risk of strabismus diagnosis (HR, 1.49; 95\% CI, 1.23-1.81; p \&lt; 0.001) and surgery (HR, 2.53; 95\% CI, 1.27-5.03; p = 0.008). CONCLUSIONS: This registry-based analysis found that individuals undergoing lower eyelid blepharoplasty were at higher risk of strabismus compared with those undergoing upper eyelid blepharoplasty. Using large databases to understand the incidence of complications of frequently performed procedures may improve ophthalmologists{\textquoteright} ability to provide data-driven counseling on surgical risks prior to intervention.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002617},
	author = {Oke, Isdin and Tobias Elze and Miller, Joan W and Lorch, Alice C and Hunter, David G and Freitag, Suzanne K and Dagi, Linda R and IRIS Registry Analytic Center Consortium}
}
@article {1677696,
	title = {Factors Associated With Nasolacrimal Duct Probing Failure Among Children in the Intelligent Research in Sight Registry},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {4},
	year = {2023},
	month = {2023 Apr 01},
	pages = {342-348},
	abstract = {IMPORTANCE: Understanding the factors associated with nasolacrimal duct probing failure in young children may help inform practice patterns. OBJECTIVE: To identify factors associated with repeated nasolacrimal duct probing in young children. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed data from the Intelligent Research in Sight (IRIS) Registry for all children who underwent nasolacrimal duct probing before 4 years of age between January 1, 2013, and December 31, 2020. MAIN OUTCOMES AND MEASURES: The Kaplan-Meier estimator was used to assess the cumulative incidence of a repeated procedure within 2 years of the initial procedure. Hazard ratios (HRs) derived from multivariable Cox proportional hazards regression models were used to evaluate the association between repeated probing and patient age, sex, race and ethnicity, geographic region, operative side, laterality of obstruction, type of initial procedure, and surgeon volume. RESULTS: This study included 19 357 children (9823 [50.7\%] male; mean [SD] age, 1.40 [0.74] years) undergoing nasolacrimal duct probing. The cumulative incidence of repeated nasolacrimal duct probing was 7.2\% (95\% CI, 6.8\%-7.5\%) within 2 years of the initial procedure. Among 1333 repeated procedures, the second procedure involved silicone intubation in 669 (50.2\%) and balloon catheter dilation in 256 (19.2\%). Among 12 008 children aged 1 year or younger, office-based simple probing was associated with a slightly higher probability of reoperation compared with facility-based simple probing (9.5\% [95\% CI, 8.2\%-10.8\%] vs 7.1\% [95\% CI, 6.5\%-7.7\%]; P \&lt; .001). In the multivariable model, a greater risk of repeated probing was associated with bilateral obstruction (HR, 1.48; 95\% CI, 1.32-1.65; P \&lt; .001) and office-based simple probing (HR, 1.33; 95\% CI, 1.13-1.55; P \&lt; .001), and a lower risk was associated with primary balloon catheter dilation (HR, 0.69; 95\% CI, 0.56-0.85; P \&lt; .001) and procedures performed by high-volume surgeons (HR, 0.84; 95\% CI, 0.73-0.97; P = .02). Age, sex, race and ethnicity, geographic region, and operative side were not associated with reoperation risk in the multivariable model. CONCLUSIONS AND RELEVANCE: In this cohort study, most children in the IRIS Registry undergoing nasolacrimal duct probing before 4 years of age did not require any additional intervention. Factors associated with lower risk of reoperation include surgeon experience, probing performed under anesthesia, and primary balloon catheter dilation.},
	keywords = {Child, Child, Preschool, Cohort Studies, Dacryocystorhinostomy, Female, Humans, Infant, Intubation, Lacrimal Duct Obstruction, Male, Nasolacrimal Duct, Retrospective Studies, Treatment Outcome},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.0004},
	author = {Oke, Isdin and Tobias Elze and Miller, Joan W and Lorch, Alice C and Hunter, David G and Elliott, Alexandra T and IRIS Registry Analytic Center Consortium}
}
@article {1773611,
	title = {Comment on "Salary Negotiations: Gender Differences in Attitudes, Priorities and Behaviors of Ophthalmologists"},
	journal = {Am J Ophthalmol},
	year = {2023},
	month = {2023 Oct 18},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.09.028},
	author = {Oke, Isdin and Tisdale, Alanna K}
}
@article {1647889,
	title = {The Pursuit of Generalizability and Equity Through Artificial Intelligence-Based Risk Prediction Models},
	journal = {JAMA Ophthalmol},
	year = {2022},
	month = {2022 Jul 07},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.2139},
	author = {Oke, Isdin}
}
@article {1661852,
	title = {Risk Factors for Retinal Detachment Repair After Pediatric Cataract Surgery in the United States},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {4},
	year = {2022},
	month = {2022 Dec},
	pages = {100203},
	abstract = {PURPOSE: To determine the cumulative incidence of retinal detachment (RD) repair following pediatric cataract surgery and identify the associated risk factors. DESIGN: US population-based insurance claims retrospective cohort study. PARTICIPANTS: Patients <= 18 years old who underwent cataract surgery in 2 large databases: Optum Clinformatics (2003-2021) and IBM MarketScan (2007-2016). METHODS: Individuals with >= 6\&nbsp;months of prior enrollment were included, and those with a history of RD, RD repair, traumatic cataract, spherophakia, or ectopia lentis were excluded. The primary outcome was time between initial cataract surgery and RD repair. The risk factors investigated included age, sex, persistent fetal vasculature (PFV), prematurity, intraocular lens (IOL) placement, and pars plana lensectomy approach. MAIN OUTCOME MEASURES: Kaplan-Meier estimated cumulative incidence of RD repair 5\&nbsp;years after cataract surgery and hazard ratios (HRs) with 95\% confidence intervals (CIs) from multivariable Cox proportional hazards regression models. RESULTS: Retinal detachment repair was performed on 47 of 3289 children included in this study. The cumulative incidence of RD repair within 5\&nbsp;years of cataract surgery was 2.0\% (95\% CI, 1.3\%-2.6\%). Children requiring RD repair were more likely to have a history of prematurity or PFV and less likely to have an IOL placed (all P\&nbsp;\&lt;\&nbsp;0.001). Factors associated with RD repair in the multivariable analysis included a history of prematurity (HR, 6.89; 95\% CI, 3.26-14.56; P \&lt; 0.001), PFV diagnosis (HR, 8.20; 95\% CI, 4.11-16.37; P \&lt; 0.001), and IOL placement (HR, 0.44; 95\% CI, 0.21-0.91; P\&nbsp;=\&nbsp;0.03). Age at surgery, sex, and pars plana lensectomy approach were not significantly associated with RD repair after adjusting for all other covariates. CONCLUSIONS: Approximately 2\% of patients will undergo RD repair within 5\&nbsp;years of pediatric cataract surgery. Children with a history of PFV and prematurity undergoing cataract surgery without IOL placement are at the greatest risk.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100203},
	author = {Oke, Isdin and Hwang, Bryce and Heo, Hwan and Nguyen, Angeline and Lambert, Scott R}
}
@article {1658654,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {130},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {e14},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.10.022},
	author = {Oke, Isdin and Hall, Nathan and Miller, Joan W and Lorch, Alice C and Hunter, David G}
}
@article {1043256,
	title = {Treatment of Ocular Pyogenic Granuloma With Topical Timolol},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {4},
	year = {2017},
	month = {2017 Apr 01},
	pages = {383-385},
	abstract = {Importance: Pyogenic granulomas, acquired vascular lesions, form on the ocular or palpebral surface related to inflammation from chalazia, trauma, or surgery. They can be unsightly, spontaneously bleed, and cause irritation to patients. Observations: A case series is presented of 4 consecutive children with acquired ocular surface pyogenic granulomas treated at Boston Children{\textquoteright}s Hospital from 2014 to 2016 with only topical timolol, 0.5\%, twice daily for a minimum of 21 days. In all cases, complete resolution occurred within the treatment period with no recurrence for at least 3 months. There were no adverse effects from the timolol during follow-up. Conclusions and Relevance: This case series of 4 children, while limited to no greater than 12 weeks of follow-up and without control children, suggests that ocular surface pyogenic granulomas respond to topical timolol treatment, which has a lower adverse-effect profile than conventional topical steroid treatments or other medical or surgical therapies. If confirmed in larger studies with longer follow-up and controls, this may be the desired treatment modality.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.0110},
	author = {Oke, Isdin and Alkharashi, Maan and Petersen, Robert A and Ashenberg, Alena and Shah, Ankoor S}
}
@article {1638564,
	title = {DryEyeRhythm: A reliable and valid smartphone application for the diagnosis assistance of dry eye},
	journal = {Ocul Surf},
	year = {2022},
	month = {2022 Apr 25},
	abstract = {PURPOSE: Undiagnosed or inadequately treated dry eye disease (DED) decreases the quality of life. We aimed to investigate the reliability, validity, and feasibility of the DryEyeRhythm smartphone application (app) for the diagnosis assistance of DED. METHODS: This prospective, cross-sectional, observational, single-center study recruited 82 participants (42 with DED) aged >=20 years (July 2020-May 2021). Patients with a history of eyelid disorder, ptosis, mental disease, Parkinson{\textquoteright}s disease, or any other disease affecting blinking were excluded. Participants underwent DED examinations, including the Japanese version of the Ocular Surface Disease Index (J-OSDI) and maximum blink interval (MBI). We analyzed their app-based J-OSDI and MBI results. Internal consistency reliability and concurrent validity were evaluated using Cronbach{\textquoteright}s alpha coefficients and Pearson{\textquoteright}s test, respectively. The discriminant validity of the app-based DED diagnosis was assessed by comparing the results of the clinical-based J-OSDI and MBI. The app feasibility and screening performance were evaluated using the precision rate and receiver operating characteristic curve analysis. RESULTS: The app-based J-OSDI showed good internal consistency (Cronbach{\textquoteright}s α = 0.874). The app-based J-OSDI and MBI were positively correlated with their clinical-based counterparts (r = 0.891 and r = 0.329, respectively). Discriminant validity of the app-based J-OSDI and MBI yielded significantly higher total scores for the DED cohort (8.6 {\textpm} 9.3 vs. 28.4 {\textpm} 14.9, P \&lt; 0.001; 19.0 {\textpm} 11.1 vs. 13.2 {\textpm} 9.3, P \&lt; 0.001). The app{\textquoteright}s positive and negative predictive values were 91.3\% and 69.1\%, respectively. The area under the curve (95\% confidence interval) was 0.910 (0.846-0.973) with concurrent use of the app-based J-OSDI and MBI. CONCLUSIONS: DryEyeRhythm app is a novel, non-invasive, reliable, and valid instrument for assessing DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2022.04.005},
	author = {Okumura, Yuichi and Inomata, Takenori and Midorikawa-Inomata, Akie and Sung, Jaemyoung and Fujio, Kenta and Akasaki, Yasutsugu and Nakamura, Masahiro and Iwagami, Masao and Fujimoto, Keiichi and Eguchi, Atsuko and Miura, Maria and Nagino, Ken and Hirosawa, Kunihiko and Huang, Tianxiang and Kuwahara, Mizu and Dana, Reza and Murakami, Akira}
}
@article {1319477,
	title = {Microglia inhibit photoreceptor cell death and regulate immune cell infiltration in response to retinal detachment},
	journal = {Proc Natl Acad Sci U S A},
	volume = {115},
	number = {27},
	year = {2018},
	month = {2018 Jul 03},
	pages = {E6264-E6273},
	abstract = {Retinal detachment (RD) is a sight-threatening complication common in many highly prevalent retinal disorders. RD rapidly leads to photoreceptor cell death beginning within 12 h following detachment. In patients with sustained RD, progressive visual decline due to photoreceptor cell death is common, leading to significant and permanent loss of vision. Microglia are the resident immune cells of the central nervous system, including the retina, and function in the homeostatic maintenance of the neuro-retinal microenvironment. It is known that microglia become activated and change their morphology in retinal diseases. However, the function of activated microglia in RD is incompletely understood, in part because of the lack of microglia-specific markers. Here, using the newly identified microglia marker P2ry12 and microglial depletion strategies, we demonstrate that retinal microglia are rapidly activated in response to RD and migrate into the injured area within 24 h post-RD, where they closely associate with infiltrating macrophages, a population distinct from microglia. Once in the injured photoreceptor layer, activated microglia can be observed to contain autofluorescence within their cell bodies, suggesting they function to phagocytose injured or dying photoreceptors. Depletion of retinal microglia results in increased disease severity and inhibition of macrophage infiltration, suggesting that microglia are involved in regulating neuroinflammation in the retina. Our work identifies that microglia mediate photoreceptor survival in RD and suggests that this effect may be due to microglial regulation of immune cells and photoreceptor phagocytosis.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1719601115},
	author = {Okunuki, Yoko and Mukai, Ryo and Pearsall, Elizabeth A and Klokman, Garrett and Husain, Deeba and Park, Dong-Ho and Korobkina, Ekaterina and Weiner, Howard L and Butovsky, Oleg and Ksander, Bruce R and Miller, Joan W and Connor, Kip M}
}
@article {1435412,
	title = {Retinal microglia initiate neuroinflammation in ocular autoimmunity},
	journal = {Proc Natl Acad Sci U S A},
	volume = {116},
	number = {20},
	year = {2019},
	month = {2019 May 14},
	pages = {9989-9998},
	abstract = {Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. While microglia have been studied extensively in autoimmune uveitis, their exact function remains uncertain. The objective of the current study was to determine whether resident microglia are necessary and sufficient to initiate and amplify retinal inflammation in autoimmune uveitis. In this study, we clearly demonstrate that microglia are essential for initiating infiltration of immune cells utilizing a murine model of experimental autoimmune uveoretinitis (EAU) and the recently identified microglia-specific marker P2ry12. Initiating disease is the primary function of microglia in EAU, since eliminating microglia during the later stages of EAU had little effect, indicating that the function of circulating leukocytes is to amplify and sustain destructive inflammation once microglia have triggered disease. In the absence of microglia, uveitis does not develop, since leukocytes cannot gain entry through the blood-retinal barrier, illustrating that microglia play a critical role in regulating infiltration of inflammatory cells into the retina.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1820387116},
	author = {Okunuki, Yoko and Mukai, Ryo and Nakao, Takeshi and Tabor, Steven J and Butovsky, Oleg and Dana, Reza and Ksander, Bruce R and Connor, Kip M}
}
@article {1623348,
	title = {TheraPearl Eye Mask and Blephasteam for the treatment of meibomian gland dysfunction: a randomized, comparative clinical trial},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Nov 17},
	pages = {22386},
	abstract = {Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED). In this study, we aimed to compare the effects of eyelid warming treatment using either TheraPearl Eye Mask (Bausch \&amp; Lomb Inc., New York, USA) or Blephasteam (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) in a Norwegian population with mild to moderate MGD-related DED. An open label, randomized comparative trial with seventy patients (49 females, 21 males; mean age 53.6\&nbsp;years). Patients were randomly assigned to treatment with Blephasteam (n = 37) or TheraPearl (n = 33). All received a hyaluronic acid based artificial tear substitute (Hylo-Comod, Ursapharm, Saarbr{\"u}cken, Germany). Patients were examined at baseline, and at three and six months initiation of treatment. Treatment efficacy was primarily evaluated by fluorescein breakup time (FBUT) and Ocular Surface Disease Index (OSDI) scores. Other outcome measures included ocular surface staining (OSS), Schirmer{\textquoteright}s test, and meibomian quality and expressibility. Baseline parameter values did not differ between the groups. After six months of treatment, Blephasteam improved FBUT by 3.9\&nbsp;s (p \&lt; 0.01) and OSDI by 13.7 (p \&lt; 0.01), TheraPearl improved FBUT by 2.6\&nbsp;s (p \&lt; 0.01) and OSDI by 12.6 (p \&lt; 0.01). No difference between treatments was detected at 6 months (p = 0.11 for FBUT and p = 0.71 for OSDI), nor were there differences in the other tested parameters between the treatment groups. Blephasteam and TheraPearl are equally effective in treating mild to moderate MGD in a Norwegian population after 6-months of treatment.Clinicaltrials.gov ID: NCT03318874; Protocol ID: 2014/1983; First registration: 24/10/2017.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-01899-8},
	author = {Olafsson, Jonatan and Lai, Xiaoran and Landsend, Erlend Christoffer Sommer and Olafsson, Snorri and Parissi, Eric and Utheim, {\O}ygunn A and Raeder, Sten and Badian, Reza A and Lagali, Neil and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1078791,
	title = {The nuclear hormone receptor gene Nr2c1 (Tr2) is a critical regulator of early retina cell patterning},
	journal = {Dev Biol},
	volume = {429},
	number = {1},
	year = {2017},
	month = {2017 Sep 01},
	pages = {343-355},
	abstract = {Nuclear hormone receptors play a major role in the development of many tissues. This study uncovers a novel role for testicular receptor 2 (Tr2, Nr2c1) in defining the early phase of retinal development and regulating normal retinal cell patterning and topography. The mammalian retina undergoes an overlapping yet biphasic period of development to generate all seven retinal cell types. We discovered that Nr2c1 expression coincides with development of the early retinal cells. Loss of Nr2c1 causes a severe vision deficit and impacts early, but not late retina cell types. Retinal cone cell topography is disrupted with an increase in displaced amacrine cells. Additionally, genetic background significantly impacts phenotypic outcome of cone photoreceptor cells but not amacrine cells. Chromatin-IP experiments reveal NR2C1 regulates early cell transcription factors that regulate retinal progenitor cells during development, including amacrine (Satb2) and cone photoreceptor regulators thyroid and retinoic acid receptors. This study supports a role for Nr2c1 in defining the biphasic period of retinal development and specifically influencing the early phase of retinal cell fate.},
	issn = {1095-564X},
	doi = {10.1016/j.ydbio.2017.05.021},
	author = {Olivares, Ana Maria and Han, Yinan and Soto, David and Flattery, Kyle and Marini, Joseph and Molemma, Nissa and Haider, Ali and Escher, Pascal and Deangelis, Margaret M and Haider, Neena B}
}
@article {705101,
	title = {Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases.},
	journal = {J Exp Neurosci},
	volume = {9},
	number = {Suppl 2},
	year = {2015},
	month = {2015},
	pages = {93-121},
	abstract = {The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.},
	issn = {1179-0695},
	doi = {10.4137/JEN.S25480},
	author = {Olivares, Ana Maria and Moreno-Ramos, Oscar Andr{\'e}s and Haider, Neena B}
}
@article {1059786,
	title = {Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Apr 06},
	pages = {690},
	abstract = {Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD). The mouse models lack key NHRS (Nr2e3, RORA) or epigenetic (Ezh2) factors. Fifty-four total miRNAs were differentially expressed, potentially targeting over 150 genes in 18 major representative networks including angiogenesis, metabolism, and immunity. We identified sixty-eight genes and 5 miRNAS directly regulated by NR2E3 and/or RORA. After a comprehensive analysis, we discovered multimodal regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD. These studies provide insight into the complex, dynamic modulation of gene networks as well as their impact on human disease, and provide novel data for the development of innovative and more effective therapeutics.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-00788-3},
	author = {Olivares, A M and Jelcick, A S and Reinecke, J and Leehy, B and Haider, A and Morrison, M A and Cheng, L and Chen, D F and DeAngelis, M M and Haider, N B}
}
@article {1125371,
	title = {Corrigendum to "The Nuclear Hormone Receptor Nr2c1 (Tr2) is a critical regulator of early retina cell pattering" [Dev. Biol. 16 (2017) 30797-7]},
	journal = {Dev Biol},
	volume = {429},
	number = {1},
	year = {2017},
	month = {2017 Sep 01},
	pages = {370},
	issn = {1095-564X},
	doi = {10.1016/j.ydbio.2017.07.009},
	author = {Olivares, Ana Maria and Han, Yinan and Soto, David and Flattery, Kyle and Marini, Joseph and Molemma, Nissa and Haider, Ali and Escher, Pascal and Deangelis, Margaret M and Haider, Neena B}
}
@article {1154951,
	title = {Animal Models of Diabetic Retinopathy},
	journal = {Curr Diab Rep},
	volume = {17},
	number = {10},
	year = {2017},
	month = {2017 Aug 24},
	pages = {93},
	abstract = {PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. RECENT FINDINGS: Rodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. DR results in vascular changes and dysfunction of the neural, glial, and pancreatic β cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.},
	issn = {1539-0829},
	doi = {10.1007/s11892-017-0913-0},
	author = {Olivares, Ana Maria and Althoff, Kristen and Chen, Gloria Fanghua and Wu, Siqi and Morrisson, Margaux A and Deangelis, Margaret M and Haider, Neena}
}
@article {1364521,
	title = {The use of fourth-generation optical coherence tomography in multiple sclerosis: a review},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {187-91},
	abstract = {Optical coherence tomography (OCT) has been routinely used to obtain high spatial resolution images of the retina and choroid non-invasively. Within the past decade, a fourth-generation OCT device using Fourier domain (FD) analysis has been developed that provides higher velocity and higher axial resolution images with better reproducibility than the previous generation time domain (TD) OCT technology. This review addresses the use of fourth-generation, FD ocular OCT in patients with multiple sclerosis.},
	keywords = {Axons, Fourier Analysis, Humans, Multiple Sclerosis, Optic Neuritis, Radiography, Retinal Ganglion Cells, Tomography, Optical Coherence},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.708808},
	author = {Oliveira, Cristiano and Cestari, Dean M and Rizzo, Joseph F}
}
@article {1645473,
	title = {Signaling Pathways Used by the Specialized Pro-Resolving Mediator Maresin 2 Regulate Goblet Cell Function: Comparison with Maresin 1},
	journal = {Int J Mol Sci},
	volume = {23},
	number = {11},
	year = {2022},
	month = {2022 Jun 02},
	abstract = {Specialized pro-resolving mediators (SPMs), including Maresins (MaR)-1 and 2, contribute to tear film homeostasis and resolve conjunctival inflammation. We investigated MaR2{\textquoteright}s signaling pathways in goblet cells (GC) from rat conjunctiva. Agonist-induced [Ca2+]i and high-molecular weight glycoconjugate secretion were measured. MaR2 increased [Ca2+]i and stimulated secretion. MaR2 and MaR1 stimulate conjunctival goblet cell function, especially secretion, by activating different but overlapping GPCR and signaling pathways, and furthermore counter-regulate histamine stimulated increase in [Ca2+]i. Thus, MaR2 and MaR1 play a role in maintaining the ocular surface and tear film homeostasis in health and disease. As MaR2 and MaR1 modulate conjunctival goblet cell function, they each may have potential as novel, but differing, options for the treatment of ocular surface inflammatory diseases including allergic conjunctivitis and dry eye disease. We conclude that in conjunctival GC MaR2 and MaR1, both increase the [Ca2+]i and stimulate secretion to maintain homeostasis by using one set of different, but overlapping, signaling pathways to increase [Ca2+]i and another set to stimulate secretion. MaR2 also resolves ocular allergy.},
	keywords = {Animals, Cells, Cultured, Conjunctiva, Docosahexaenoic Acids, Goblet Cells, Mucins, Rats, Rats, Sprague-Dawley, Signal Transduction},
	issn = {1422-0067},
	doi = {10.3390/ijms23116233},
	author = {Olsen, Markus V and Lyngstadaas, Anne V and Bair, Jeffrey A and Hodges, Robin R and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1517190,
	title = {Maresin 1, a specialized proresolving mediator, stimulates intracellular [Ca ] and secretion in conjunctival goblet cells},
	journal = {J Cell Physiol},
	volume = {236},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {340-353},
	abstract = {Mucin secretion from conjunctival goblet cells forms the tear film mucin layer and requires regulation to function properly. Maresin 1 (MaR1) is a specialized proresolving mediator produced during the resolution of inflammation. We determined if MaR1 stimulates mucin secretion and signaling pathways used. Cultured rat conjunctival goblet cells were used to measure the increase in intracellular Ca ([Ca ] ) concentration and mucin secretion. MaR1-increased [Ca ] and secretion were blocked by inhibitors of phospholipase C, protein kinase C, Ca /calmodulin-dependent protein kinase II, and extracellular-regulated kinase 1/2. MaR1 added before addition of histamine counterregulated histamine-stimulated increase in [Ca ] and secretion. We conclude that MaR1 likely has two actions in conjunctival goblet cells: first, maintaining optimal tear film mucin levels by increasing [Ca ] and stimulating mucin secretion in health and, second, attenuating the increase in [Ca ] and overproduction of mucin secretion by counterregulating the effect of histamine as occurs in ocular allergy.},
	issn = {1097-4652},
	doi = {10.1002/jcp.29846},
	author = {Olsen, Markus V and Lyngstadaas, Anne V and Bair, Jeffrey A and Hodges, Robin R and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1593858,
	title = {Cerebral visual impairment in CDKL5 deficiency disorder: vision as an outcome measure},
	journal = {Dev Med Child Neurol},
	volume = {63},
	number = {11},
	year = {2021},
	month = {2021 Nov},
	pages = {1308-1315},
	abstract = {AIM: To characterize the neuro-ophthalmological phenotype of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) and assess visual acuity as a reproducible, quantitative outcome measure. METHOD: We retrospectively analyzed clinical data from patients with CDD. Complete neuro-ophthalmological assessments, including visual acuity, were evaluated. RESULTS: Of 26 patients (22 females, four males; median age 4y, interquartile range 2y 1mo-7y 10mo), cerebral visual impairment (CVI), defined as visual dysfunction in the absence of ocular or anterior visual pathway abnormalities, was diagnosed in all those over 2\&nbsp;years of age. Ophthalmological examinations revealed nystagmus in 10 patients and strabismus in 24 patients. Visual acuity was measured in 24 patients, by preferential looking in all and by sweep visual evoked potential in 13. Visual acuities were lower than age expectations and demonstrated improvement in the first 3\&nbsp;years. Adjusting for age and sex, average preferential looking visual acuity after 2\&nbsp;years of age was higher in patients with intact mobility than in those who were non-mobile. INTERPRETATION: CVI was observed in patients with CDD. Visual acuity improved over time and correlated with mobility. Visual acuity, as a quantifiable measure of visual function, should be considered as an outcome measure in pre-clinical and clinical studies for CDD. What this paper adds Cerebral visual impairment is highly prevalent in cyclin-dependent kinase-like 5 deficiency disorder (CDD). Visual acuity is a measurable quantitative outcome measure in CDD. Visual acuity in CDD correlates with gross motor ability.},
	issn = {1469-8749},
	doi = {10.1111/dmcn.14908},
	author = {Olson, Heather E and Costantini, Julia G and Swanson, Lindsay C and Kaufmann, Walter E and Benke, Timothy A and Fulton, Anne B and Hansen, Ronald and Poduri, Annapurna and Heidary, Gena}
}
@article {1016111,
	title = {Cataract in the Adult Eye Preferred Practice Pattern{\textregistered}},
	journal = {Ophthalmology},
	volume = {124},
	number = {2},
	year = {2017},
	month = {2017 Feb},
	pages = {P1-P119},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.09.027},
	author = {Olson, Randall J and Braga-Mele, Rosa and Chen, Sherleen Huang and Miller, Kevin M and Pineda, Roberto and Tweeten, James P and Musch, David C}
}
@article {1078796,
	title = {Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair in Corneal Injury},
	journal = {Mol Ther},
	volume = {25},
	number = {8},
	year = {2017},
	month = {2017 Aug 02},
	pages = {1881-1888},
	abstract = {Corneal injuries are among the major causes of ocular morbidity and vision impairment. Optimal epithelial wound healing is critical for the integrity and transparency of the cornea after injury. Hepatocyte growth factor (HGF) is a mitogen and motility factor that primarily regulates epithelial cell function. Herein, we investigate the effect of HGF on proliferation of corneal epithelial cells (CECs) in inflamed conditions both in\&nbsp;vitro and in\&nbsp;vivo. We demonstrate that HGF not only promotes CEC proliferation in homeostatic conditions but also reverses the anti-proliferative effect of the inflammatory environment on these cells. Furthermore, using a mouse model of ocular injury, we show that HGF treatment suppresses ocular inflammation and actively augments CEC proliferation, leading to improved and accelerated corneal epithelial repair. These findings have potential translational implications and could provide a framework for the development of novel HGF-based therapies for corneal epithelial defects.},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2017.04.020},
	author = {Omoto, Masahiro and Suri, Kunal and Amouzegar, Afsaneh and Li, Mingshun and Katikireddy, Kishore R and Mittal, Sharad K and Chauhan, Sunil K}
}
@article {280706,
	title = {Mesenchymal stem cells home to inflamed ocular surface and suppress allosensitization in corneal transplantation.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2014},
	month = {2014 Sep 16},
	abstract = {Purpose: To investigate whether systemically-injected syngeneic mesenchymal stem cells (MSCs) can home to the inflamed transplanted cornea, suppress induction of alloimmunity, and promote allograft survival. Methods: MSCs were generated from bone marrow of wild-type BALB/c or GFP+ C57BL/6 mice, and 1x106 cells were intravenously injected to allografted recipients 3 hours after surgery. MSCs homing to the cornea were examined at day 3 post-transplantation by immunohistochemistry. CD11c+MHC II+ cells were detected in the cornea and lymph nodes (LNs) 14 days post-transplantation using flow cytometry. Cytokine expression of bone marrow-derived dendritic cells (BMDCs) was determined using real-time PCR. ELISPOT assay was used to assess indirect and direct host T cell allosensitization, and graft survival was evaluated by slit-lamp biomicroscopy weekly up to 8 weeks. Results: Intravenously injected GFP+ MSCs were found in abundance in the transplanted cornea, conjunctiva, and lymph nodes, but not in the ungrafted (contralateral) tissue. The frequencies of mature CD11c+MHC II+ APCs were substantially decreased in the corneas and draining LNs of MSC-injected allograft recipients compared to control recipients. Maturation and function of in vitro cultured BMDCs was decreased when cocultured with MSCs. Draining LNs of MSC-injected allograft recipients showed significantly lower frequencies of IFNγ-secreting Th1 cells compared to the control group. Allograft survival rate was significantly higher in MSC-injected recipients compared to non-MSC injected recipients. Conclusions: Our data demonstrate that systemically-administered MSCs specifically home to transplanted corneas and promote allograft survival by inhibiting APC maturation and induction of alloreactive T cells.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15413},
	author = {Omoto, Masahiro and Katikireddy, Kishore R and Rezazadeh, Alexandra and Dohlman, Thomas H and Chauhan, Sunil}
}
@article {1586145,
	title = {Lens extraction for chronic angle-closure glaucoma},
	journal = {Cochrane Database Syst Rev},
	volume = {3},
	year = {2021},
	month = {2021 Mar 24},
	pages = {CD005555},
	abstract = {BACKGROUND: Primary angle-closure glaucoma (PACG) is characterized by a rise in intraocular pressure (IOP) secondary to aqueous outflow obstruction, with relative pupillary block being the most common underlying mechanism. There is increasing evidence that lens extraction may relieve pupillary block and thereby improve IOP control. As such, comparing the effectiveness of lens extraction against other commonly used treatment modalities can help inform the decision-making process. OBJECTIVES: To assess the effectiveness of lens extraction compared with other interventions in the treatment of chronic PACG in people without previous acute angle-closure attacks. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and two trials registers (December 2019). We also screened the reference lists of included studies and the Science Citation Index database. We had no date or language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing lens extraction with other treatment modalities for chronic PACG. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We identified eight RCTs with 914 eyes. We obtained data for participants meeting our inclusion criteria for these studies (PACG only, no previous acute angle-closure attacks), resulting in 513 eyes included in this review. The participants were recruited from a diverse range of countries. We were unable to conduct meta-analyses due to different follow-up periods and insufficient data. One study compared phacoemulsification with laser peripheral iridotomy (LPI) as standard care. Participants in the phacoemulsification group were less likely to experience progression of visual field loss (odds ratio [OR] 0.35, 95\% confidence interval [CI] 0.13 to 0.91; 216 eyes; moderate certainty evidence), and required fewer IOP-lowering medications (mean difference [MD] -0.70, 95\% CI -0.89 to -0.51; 263 eyes; moderate certainty evidence) compared with standard care at 12 months. Moderate certainty evidence also suggested that phacoemulsification improved gonioscopic findings at 12 months or later (MD -84.93, 95\% CI -131.25 to -38.61; 106 eyes). There was little to no difference in health-related quality of life measures (MD 0.04, 95\% CI -0.16 to 0.24; 254 eyes; moderate certainty evidence), and visual acuity (VA) (MD 2.03 ETDRS letter, 95\% CI -0.77 to 4.84; 242 eyes) at 12 months, and no observable difference in mean IOP (MD -0.03mmHg, 95\% CI -2.34 to 2.32; 257 eyes; moderate certainty evidence) compared to standard care. Irreversible loss of vision was observed in one participant in the phacoemulsification group, and three participants in standard care at 36 months (moderate-certainty evidence). One study (91 eyes) compared phacoemulsification with phaco-viscogonioplasty (phaco-VGP). Low-certainty evidence suggested that fewer IOP-lowering medications were needed at 12 months with phacoemulsification (MD -0.30, 95\% CI -0.55 to -0.05). Low-certainty evidence also suggested that phacoemulsification may have improved gonioscopic findings at 12 months or later compared to phaco-VGP (angle grading MD -0.60, 95\% CI -0.91 to -0.29; TISA500 MD -0.03, 95\% CI -0.06 to -0.01; TISA750 MD -0.03, 95\% CI -0.06 to -0.01; 91 eyes). Phacoemulsification may result in little to no difference in best corrected VA at 12 months (MD -0.01 log MAR units, 95\% CI -0.10 to 0.08; low certainty evidence), and the evidence is very uncertain about its effect on IOP at 12 months (MD 0.50 mmHg, 95\% CI -2.64 to 3.64; very low certainty evidence). Postoperative fibrin reaction was observed in two participants in the phacoemulsification group and four in the phaco-VGP group. Three participants in the phaco-VGP group experienced hyphema. No data were available for progression of visual field loss and quality of life measurements at 12 months. Two studies compared phacoemulsification with phaco-goniosynechialysis (phaco-GSL). Low-certainty evidence suggested that there may be little to no difference in mean IOP at 12 months (MD -0.12 mmHg, 95\% CI -4.72 to 4.48; 1 study, 32 eyes) between the interventions. Phacoemulsification did not reduce the number of IOP-lowering medications compared to phaco-GSL at 12 months (MD -0.38, 95\% CI -1.23 to 0.47; 1 study, 32 eyes; moderate certainty evidence). Three eyes in the phaco-GSL group developed hyphemas. No data were available at 12 months for progression of visual field loss, gonioscopic findings, visual acuity, and quality of life measures. Three studies compared phacoemulsification with combined phaco-trabeculectomy, but the data were only available for one study (63 eyes). In this study, low-certainty evidence suggested that there was little to no difference between groups in mean change in IOP from baseline (MD -0.60 mmHg, 95\% CI -1.99 to 0.79), number of IOP-lowering medications at 12 months (MD 0.00, 95\% CI -0.42 to 0.42), and VA measured by the Snellen chart (MD -0.03, 95\% CI -0.18 to 0.12). Participants in the phacoemulsification group had fewer complications (risk ratio [RR] 0.59, 95\% CI 0.34 to 1.04), and the phaco-trabeculectomy group required more IOP-lowering procedures (RR 5.81, 95\% CI 1.41 to 23.88), but the evidence was very uncertain. No data were available for other outcomes. AUTHORS{\textquoteright} CONCLUSIONS: Moderate certainty evidence showed that lens extraction has an advantage over LPI in treating chronic PACG with clear crystalline lenses over three years of follow-up; ultimately, the decision for intervention should be part of a shared decision-making process between the clinician and the patient. For people with chronic PACG and visually significant cataracts, low certainty evidence suggested that combining phacoemulsification with either viscogonioplasty or goniosynechialysis does not confer any additional benefit over phacoemulsification alone. There was insufficient evidence to draw any meaningful conclusions regarding phacoemulsification versus trabeculectomy. Low certainty evidence suggested that combining phacoemulsification with trabeculectomy does not confer any additional benefit over phacoemulsification alone, and may cause more complications instead. These conclusions only apply to short- to medium-term outcomes; studies with longer follow-up periods can help assess whether these effects persist in the long term.},
	issn = {1469-493X},
	doi = {10.1002/14651858.CD005555.pub3},
	author = {Ong, Ariel Yuhan and Ng, Sueko M and Vedula, Swaroop S and Friedman, David S}
}
@article {1677686,
	title = {Lens extraction versus laser peripheral iridotomy for acute primary angle closure},
	journal = {Cochrane Database Syst Rev},
	volume = {3},
	number = {3},
	year = {2023},
	month = {2023 Mar 08},
	pages = {CD015116},
	abstract = {BACKGROUND: Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process.\&nbsp; OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 1), Ovid MEDLINE, Ovid MEDLINE E-pub Ahead of Print, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to 10 January 2022), Embase (January 1947 to 10 January 2022), PubMed (1946 to 10 January 2022), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 10 January 2022), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 10 January 2022. SELECTION CRITERIA: We included randomized controlled clinical trials comparing lens extraction against LPI in adult participants ( >= 35 years) with APAC in one or both eyes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS: We included two studies conducted in Hong Kong and Singapore, comprising 99 eyes (99 participants) of predominantly Chinese origin. The two studies compared LPI with phacoemulsification performed by experienced surgeons. We assessed that both studies were at high risk of bias. There were no studies evaluating other types of lens extraction procedures.\&nbsp; Phacoemulsification may result in an increased proportion of participants with intraocular pressure (IOP) control compared with LPI at 18 to 24 months (risk ratio (RR) 1.66, 95\% confidence interval (CI) 1.28 to 2.15; 2 studies, n = 97; low certainty evidence) and may reduce the need for further IOP-lowering surgery within 24 months (RR 0.07, 96\% CI 0.01 to 0.51; 2 studies, n = 99; very low certainty evidence). Phacoemulsification may result in a lower mean IOP at 12 months compared to LPI (mean difference (MD) -3.20, 95\% CI -4.79 to -1.61; 1 study, n = 62; low certainty evidence) and a slightly lower mean number of IOP-lowering medications at 18 months (MD -0.87, 95\% CI -1.28 to -0.46; 1 study, n = 60; low certainty evidence), but this may not be clinically significant. Phacoemulsification may have little to no effect on the proportion of participants with one or more recurrent APAC episodes in the same eye (RR 0.32, 95\% CI 0.01 to 7.30; 1 study, n = 37; very low certainty evidence). Phacoemulsification may result in a wider iridocorneal angle assessed by Shaffer grading at six months (MD 1.15, 95\% CI 0.83 to 1.47; 1 study, n = 62; very low certainty evidence). Phacoemulsification may have little to no effect on logMAR best-corrected visual acuity (BCVA) at six months (MD -0.09, 95\% CI -0.20 to 0.02; 2 studies, n = 94; very low certainty evidence). There was no evidence of a difference in the extent of peripheral anterior synechiae (PAS) (clock hours) between intervention arms at 6 months (MD -1.86, 95\% CI -7.03 to 3.32; 2 studies, n = 94; very low certainty evidence), although the phacoemulsification group may have less PAS (degrees) at 12 months (MD -94.20, 95\% CI -140.37 to -48.03; 1 study, n = 62) and 18 months (MD -127.30, 95\% CI -168.91 to -85.69; 1 study, n = 60).\&nbsp; In one study, there were 26 adverse events in the phacoemulsification group: intraoperative corneal edema (n = 12), posterior capsular rupture (n = 1), intraoperative bleeding from iris root (n = 1), postoperative fibrinous anterior chamber reaction (n = 7), and visually significant posterior capsular opacification (n = 5), and no cases of suprachoroidal hemorrhage or endophthalmitis. There were four adverse events in the LPI group: closed iridotomy (n = 1) and small iridotomies that required supplementary laser (n = 3). In the other study, there was one adverse event in the phacoemulsification group (IOP \&gt; 30 mmHg on day 1 postoperatively (n = 1)), and no intraoperative complications. There were five adverse events in the LPI group: transient hemorrhage (n = 1), corneal burn (n = 1), and repeated LPI because of non-patency (n = 3).\&nbsp; Neither study reported health- or vision-related quality of life measures. AUTHORS{\textquoteright} CONCLUSIONS: Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.},
	keywords = {Adult, Cataract Extraction, Glaucoma, Humans, Intraocular Pressure, Phacoemulsification, Quality of Life},
	issn = {1469-493X},
	doi = {10.1002/14651858.CD015116.pub2},
	author = {Ong, Ariel Yuhan and McCann, Paul and Perera, Shamira A and Lim, Fiona and Ng, Sueko M and Friedman, David S and Chang, Dolly}
}
@article {1511480,
	title = {Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis},
	journal = {Prog Retin Eye Res},
	volume = {80},
	year = {2021},
	month = {2021 Jan},
	pages = {100863},
	abstract = {Fuchs endothelial corneal dystrophy (FECD) is the most common primary corneal endothelial dystrophy and the leading indication for corneal transplantation worldwide. FECD is characterized by the progressive decline of corneal endothelial cells (CECs) and the formation of extracellular matrix (ECM) excrescences in Descemet{\textquoteright}s membrane (DM), called guttae, that lead to corneal edema and loss of vision. FECD typically manifests in the fifth decades of life and has a greater incidence in women. FECD is a complex and heterogeneous genetic disease where interaction between genetic and environmental factors results in cellular apoptosis and aberrant ECM deposition. In this review, we will discuss a complex interplay of genetic, epigenetic, and exogenous factors in inciting oxidative stress, auto(mito)phagy, unfolded protein response, and mitochondrial dysfunction during CEC degeneration. Specifically, we explore the factors that influence cellular fate to undergo apoptosis, senescence, and endothelial-to-mesenchymal transition. These findings will highlight the importance of abnormal CEC-DM interactions in triggering the vicious cycle of FECD pathogenesis. We will also review clinical characteristics, diagnostic tools, and current medical and surgical management options for FECD patients. These new paradigms in FECD pathogenesis present an opportunity to develop novel therapeutics for the treatment of FECD.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2020.100863},
	author = {Ong Tone, Stephan and Kocaba, Viridiana and B{\"o}hm, Myriam and Wylegala, Adam and White, Tomas L and Jurkunas, Ula V}
}
@article {630191,
	title = {Long-term side effects of glucocorticoids.},
	journal = {Expert Opin Drug Saf},
	volume = {15},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {457-65},
	abstract = {INTRODUCTION: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible. AREAS COVERED: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment. EXPERT OPINION: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.},
	issn = {1744-764X},
	doi = {10.1517/14740338.2016.1140743},
	author = {Oray, Merih and Abusamra, Khawla and Ebrahimiadib, Nazanin and Meese, Halea and Foster, C Stephen}
}
@article {688636,
	title = {Ocular morbidities of juvenile idiopathic arthritis-associated uveitis in adulthood: results from a tertiary center study.},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {254},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1841-9},
	abstract = {PURPOSE: To describe the clinical and visual outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis in adults and to examine risk factors for ongoing inflammation in adulthood. METHODS: Medical records were reviewed for patients with JIA-associated uveitis who were \&gt;16\&nbsp;years old at the final visit (the last visit prior to data collection). RESULTS: In total, 135 eyes of 77 patients (70 female, 7 male) were included. The mean age of patients at the final visit was 29.72 {\textpm} 11.27\&nbsp;years. The number of eyes with visual acuity of <=20/50 and <=20/200 at the final visit was 37 (28\&nbsp;\%) and 20 (15\&nbsp;\%), respectively; at least one ocular complication was present in 72\&nbsp;\% of eyes. Band keratopathy was the most frequent complication (42\&nbsp;\%), followed by cataract (25\&nbsp;\%), posterior synechiae (22\&nbsp;\%), maculopathy (22\&nbsp;\%), ocular hypertension (13\&nbsp;\%), and hypotony (5\&nbsp;\%). At the final visit, patients who were \&gt;16\&nbsp;years of age at presentation to the Massachusetts Eye Research and Surgery Institution had more ocular complications and a greater degree of vision loss than patients who were <=16\&nbsp;years of age. Ongoing inflammation at the final visit was noted in 40 patients (52\&nbsp;\%). The presence of posterior synechiae, hypotony, cataract at presentation, and a history of cataract surgery prior to presentation were predictive of ongoing inflammation in adulthood in univariate analysis. The presence of hypotony and posterior synechiae at the initial visit were predictive factors in multivariate analysis. CONCLUSIONS: JIA-associated uveitis may be associated with ongoing inflammation, ocular complications, and severe visual impairment in adulthood. The presence of posterior synechiae and hypotony at the initial visit is predictive of ongoing inflammation.},
	issn = {1435-702X},
	doi = {10.1007/s00417-016-3340-z},
	author = {Oray, Merih and Khachatryan, Naira and Ebrahimiadib, Nazanin and Abusamra, Khawla and Lee, Stacey and Foster, C Stephen}
}
@article {688631,
	title = {Diagnosis and management of non-infectious immune-mediated scleritis: current status and future prospects.},
	journal = {Expert Rev Clin Immunol},
	volume = {12},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {827-37},
	abstract = {Scleritis is an inflammatory process of the sclera and adjacent tissues with a wide spectrum of clinical presentations and co-morbidities. Careful clinical history taking, detailed ocular examination, and appropriate investigation for likelihood of an underlying systemic disease are essential for diagnosis. Treatment can be quite challenging in some cases. Conventional therapy with corticosteroids and immunosuppressive agents may not be sufficient to control ocular inflammation in refractory patients. In such cases new therapeutic agents, which have a more targeted and sustained effect on the immune response, so-called biologic response modifiers, are being used. This review focuses on both diagnosis and therapeutic options including traditional and emerging therapies of non-infectious scleritis.},
	issn = {1744-8409},
	doi = {10.1586/1744666X.2016.1171713},
	author = {Oray, Merih and Meese, Halea and Foster, C Stephen}
}
@article {1351176,
	title = {Blue toe syndrome: a complication of intra-arterial technique, not intra-arterial chemotherapy for retinoblastoma},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {5},
	year = {2014},
	month = {2014 May},
	pages = {654},
	keywords = {Antineoplastic Agents, Alkylating, Blue Toe Syndrome, Catheterization, Peripheral, Humans, Male, melphalan, Retinal Neoplasms, Retinoblastoma},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.6342},
	author = {Orbach, Darren B and VanderVeen, Deborah K and Shah, Ankoor S and Rodriguez-Galindo, Carlos}
}
@article {1698306,
	title = {Fungal keratitis caused by Coniochaeta mutabilis-A case report},
	journal = {J Mycol Med},
	volume = {33},
	number = {2},
	year = {2023},
	month = {2023 May},
	pages = {101384},
	abstract = {We present a rare case of recalcitrant fungal keratitis caused by Coniochaeta mutabilis, successfully managed with a course of oral, topical, intrastromal, and intracameral antifungals. A 57-year-old male on their fourth week of treatment for presumed left herpes simplex keratitis presented to clinic with severe left-sided foreign body sensation after gardening in his yard. On examination, a white corneal plaque was observed at 8 o{\textquoteright}clock, shown to be a dense collection of fungal hyphae on confocal microscopy. Corneal cultures revealed yeast-like cells, initially identified as Kabatiella zeae by matching 100\% identity with K. zeae strains CBS 767.71 and CBS 265.32 in BLASTn search using the internal transcribed spacer (ITS) sequence. Treated for over four months with topical amphotericin B and oral voriconazole without improvement, recourse to intrastromal and intracameral amphotericin B injections, coupled with the application of cyanoacrylate glue to the lesion and a bandage contact lens, led to eventual resolution. The patient subsequently underwent cataract surgery, achieving a BCVA of 20/20 in the eye. Surprisingly, upon further sequence analyses of combined ITS and large subunit ribosomal ribonucleic acid (LSU) and investigation of the K. zeae German strain CBS 767.71, the organism was revealed to be Coniochaeta mutabilis (formerly Lecythospora mutabilis). This means that the correct name for CBS 767.71 and CBS 265.32 is C. mutabilis and should be corrected in the GenBank record to avoid misleading identification in the future. This case also underscores the urgent unmet need for improved molecular diagnostic modalities in the care of corneal infections.},
	keywords = {Amphotericin B, Antifungal Agents, Corneal Ulcer, Eye Infections, Fungal, Humans, Keratitis, Male, Middle Aged, Voriconazole},
	issn = {1773-0449},
	doi = {10.1016/j.mycmed.2023.101384},
	author = {Oremosu, Jadesola and Ung, Lawson and Chodosh, James and Ca{\~n}ete-Gibas, Connie and Wiederhold, Nathan P and Davies, Emma C and Bispo, Paulo J M}
}
@article {1709771,
	title = {A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration},
	journal = {Cell Genom},
	volume = {3},
	number = {6},
	year = {2023},
	month = {2023 Jun 14},
	pages = {100302},
	abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness, affecting 200 million people worldwide. To identify genes that could be targeted for treatment, we created a molecular atlas at different stages of AMD. Our resource is comprised of RNA sequencing (RNA-seq) and DNA methylation microarrays from bulk macular retinal pigment epithelium (RPE)/choroid of clinically phenotyped normal and AMD donor eyes (n\&nbsp;= 85), single-nucleus RNA-seq (164,399 cells), and single-nucleus assay for transposase-accessible chromatin (ATAC)-seq (125,822 cells) from the retina, RPE, and choroid of 6 AMD and 7 control donors. We identified 23 genome-wide significant loci differentially methylated in AMD, over 1,000 differentially expressed genes across different disease stages, and an AMD M{\"u}ller state distinct from normal or gliosis. Chromatin accessibility peaks in genome-wide association study (GWAS) loci revealed putative causal genes for AMD, including HTRA1 and C6orf223. Our systems biology approach uncovered molecular mechanisms underlying AMD, including regulators of WNT signaling, FRZB and TLE2, as mechanistic players in disease.},
	issn = {2666-979X},
	doi = {10.1016/j.xgen.2023.100302},
	author = {Orozco, Luz D and Owen, Leah A and Hofmann, Jeffrey and Stockwell, Amy D and Tao, Jianhua and Haller, Susan and Mukundan, Vineeth T and Clarke, Christine and Lund, Jessica and Sridhar, Akshayalakshmi and Mayba, Oleg and Barr, Julie L and Zavala, Rylee A and Graves, Elijah C and Zhang, Charles and Husami, Nadine and Finley, Robert and Au, Elizabeth and Lillvis, John H and Farkas, Michael H and Shakoor, Akbar and Sherva, Richard and Kim, Ivana K and Kaminker, Joshua S and Townsend, Michael J and Farrer, Lindsay A and Yaspan, Brian L and Chen, Hsu-Hsin and Deangelis, Margaret M}
}
@article {1504065,
	title = {Alport Syndrome and Femtosecond Laser-assisted Cataract Surgery},
	journal = {J Ophthalmic Vis Res},
	volume = {15},
	number = {2},
	year = {2020},
	month = {2020 Apr-Jun},
	pages = {264-269},
	abstract = {We report the surgical management of a patient with bilateral anterior lenticonus due to Alport syndrome using femtosecond laser-assisted cataract surgery (FLACS) and the Optiwave Refractive Analysis (ORA) system. A 38-year-old man with Alport syndrome presented to our department with visual loss due to anterior lenticonus in both eyes. Adjustments during bilateral FLACS were performed with the software{\textquoteright}s calipers to manually delineate the anterior capsulotomy. Multifocal toric intraocular lenses (IOLs) were selected and placed in the posterior chamber with the aid of intraoperative aberrometry. The intended postoperative positioning parameters for the IOL as well as the planned visual acuity and refraction were achieved. The implementation of FLACS and intraoperative wavefront aberrometry is a safe and useful surgical approach for the management of cataract in challenging cases such as patients with anterior lenticonus due to Alport syndrome.},
	issn = {2008-2010},
	doi = {10.18502/jovr.v15i2.6748},
	author = {Orts-Vila, Paz and Amparo, Francisco and Rodr{\'\i}guez-Prats, Jos{\'e} Lu{\'\i}s and Ta{\~n}{\'a}-Rivero, Pedro}
}
@article {1363168,
	title = {Comparison of methodologies in volumetric orbitometry},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {6},
	year = {2013},
	month = {2013 Nov-Dec},
	pages = {431-6},
	abstract = {PURPOSE: The rate at which the orbit matures is not well-documented. Limiting this pursuit are the difficulties inherent in measuring orbital volumes accurately. This study compared 3 common methods of determining orbital volume and sought to identify an accurate, practical manner for doing so. METHODS: The volume of 1 orbit of 8 human cadaver heads was independently measured using 3 different methods: 1) CT was performed, and images were analyzed with 3-dimensional (3D) volumetric software; 2) The same orbits were then exenterated and a silicone cast was taken. The cast volumes were measured by water displacement; 3) The orbits were then filled with 1-mm glass beads that were transferred to a graduated cylinder where their volume was determined. The data were analyzed statistically. RESULTS: Intraobserver agreements were good for both beads and casts. Interobserver agreements were good for both beads and CT (p \&gt; 0.05). Values obtained using the bead method were equal to values obtained using the cast method (p \&gt; 0.05). However, agreement between direct (orbital fillers and casts) and indirect measurements (radiographic techniques) was not satisfactory (p \&lt; 0.05). CONCLUSIONS: Independent of method, determining orbital volume is inherently difficult owing to the hyperbolic parabola that is the orbit entrance; all methods require estimation. Glass beads and casts yielded more reproducible values but can only be used in cadavers. CT measurement is prone to error due to the variability of methodologies used but allows access to enormous testing populations. Interstudy comparison is currently not possible. CT volumetric software with strict universal standards for estimating the anterior limit of the orbit appears to be the best method of studying human orbital volumes.},
	keywords = {Cadaver, Casts, Surgical, Glass, Humans, Imaging, Three-Dimensional, Observer Variation, Orbit, Silicones, Tomography, X-Ray Computed},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31829d028a},
	author = {Osaki, Tammy H and De Castro, Dawn K and Yabumoto, Cristina and Mingkwansook, Varalee and Ting, Eric and Nallasamy, Nambi and Curtin, Hugh and Fay, Aaron}
}
@article {1363169,
	title = {Immunohistochemical investigations of orbital infantile hemangiomas and adult encapsulated cavernous venous lesions (malformation versus hemangioma)},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {3},
	year = {2013},
	month = {2013 May-Jun},
	pages = {183-95},
	abstract = {PURPOSE: Immunohistochemical studies have begun to advance knowledge regarding the pathogenesis of vascular anomalies in many anatomical regions. However, the immunohistochemical features of most orbital tumors have been overlooked. Therefore, a comparative immunohistochemical study of a series of the 2 most common orbital vascular lesions- infantile hemangioma (IH) and encapsulated cavernous venous lesion (ECVL), the latter also termed cavernous hemangioma or venous malformation-was undertaken. METHODS: Twenty surgically excised orbital tumors diagnosed clinically and histopathologically as IHs (10 cases) or "cavernous hemangioma" (10 cases) were evaluated pathologically and immunohistochemically using hematoxylin and eosin, Alcian blue, Masson trichrome, GLUT-1, CD31, CD34, D2-40, smooth muscle actin (SMA), desmin, and Ki-67 probes. RESULTS: All cases reacted strongly with the traditional blood vessel endothelial markers CD31 and CD34 and were negative for D2-40, a selective marker for lymphatic endothelium. All IH were positive for GLUT-1, and all ECVL were negative for GLUT-1. In IH, SMA (but not desmin) stained a monolayer of pericytes and in ECVL multilaminar smooth muscle vascular mural cells and intravascular (interstitial) stromal cells. Nuclear Ki-67 immunostaining was strongly positive in IH (average of 16.3\%) and close to zero in ECVL. CONCLUSIONS: Immunophenotypic results for ECVL and IH demonstrated no overlapping staining patterns. Infantile hemangioma had the classical architecture of capillaries. Because of the constant presence of mural smooth muscle, it was concluded that ECVL is an accurate and descriptive term. However, desmin negativity in ECVL indicates myofibroblastic differentiation rather than full-fledged smooth muscle differentiation. Infantile hemangioma may display ectatic channels as the lesion ages but does not acquire multilaminar smooth muscle walls. Its pericytes lack cytoplasmic filaments and desmin reactivity but are SMA-positive because of the presence of poorly polymerized actin in the cytosol. In IH, Ki-67 positivity was observed in the endothelial cells of the solid and more ectatic regions. In contrast, the virtual absence of Ki-67 positivity in ECVL lends further support for the interpretation that it is more closely related to a malformation than a benign neoplasm.},
	keywords = {Actins, Adult, Aged, Antigens, CD34, Biomarkers, Tumor, Child, Preschool, Female, Glucose Transporter Type 1, Hemangioma, Hemangioma, Cavernous, Humans, Immunohistochemistry, Immunophenotyping, Infant, Ki-67 Antigen, Male, Middle Aged, Neoplasm Proteins, Ophthalmologic Surgical Procedures, Orbital Neoplasms, Platelet Endothelial Cell Adhesion Molecule-1},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31828b0f1f},
	author = {Osaki, Tammy H and Jakobiec, Frederick A and Mendoza, Pia R and Lee, Yongjae and Fay, Aaron M}
}
@article {1363170,
	title = {Orbital development as a function of age in indigenous North American skeletons},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {2},
	year = {2013},
	month = {2013 Mar-Apr},
	pages = {131-6},
	abstract = {PURPOSE: Infants with orbital hemangiomas and vascular malformations often develop expanded orbits or regional hyperostosis. Treatment in these cases depends, in part, on the stage of orbital development at the time of intervention; yet, orbital development with respect to age is not well-known. The authors sought to determine the rate of orbital development and the age of orbital maturation in a single ethnic population. METHODS: Skeletons recovered in North America and housed at the Peabody Museum of Archaeology and Ethnology, Harvard University, were inspected. The age of specimen was determined by dentition. Orbital volume was measured using 1-mm glass beads and a graduated cylinder. Linear measurements were taken with calipers and paper rulers. The measurements were plotted against age, and statistical analysis was performed. Relevant literature was reviewed. RESULTS: Of the hundreds of skeletons examined, 42 were sufficiently intact for orbital measurement. The specimens represented a period of up to 1000 years. Thirty-two were pediatric (defined prenatal to 18 years) and 10 were adults. Mean adult orbital volume was 26.2 ml. Based on the regression analysis, 60\% of adult orbital volume was achieved at 4.35 years, 75\% at 9.36 years, and 90\% at 17.13 years of age. Linear dimensions progressively increased with age. CONCLUSIONS: This largest direct-measure study of pediatric orbital volume suggests that orbital growth continually decelerates from birth until maturity at 22 years. With 50\% of orbital growth occurring by 16 months of age, surgeons removing periocular vascular anomalies after that age should consider concurrent skeletal management.},
	keywords = {Adolescent, Adult, Aging, Child, Child, Preschool, Female, Fossils, Humans, Indians, North American, Infant, Infant, Newborn, Male, Maxillofacial Development, Orbit, Organ Size, PALEONTOLOGY, Young Adult},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e3182831c49},
	author = {Osaki, Tammy H and Fay, Aaron and Mehta, Manisha and Nallasamy, Nambi and Waner, Milton and De Castro, Dawn K}
}
@article {1538332,
	title = {Genetic and nongenetic factors associated with CADASIL: A retrospective cohort study},
	journal = {J Neurol Sci},
	volume = {419},
	year = {2020},
	month = {2020 Dec 15},
	pages = {117178},
	abstract = {OBJECTIVE: To explore the role of cardiovascular risk factors and the different NOTCH-3 mutations to explain the variability observed in the clinical presentation of CADASIL. METHODS: This was a retrospective cohort study of 331 individuals, 90 were carriers of four mutations in the NOTCH3 gene. These four mutations are the ones identified in our region from the genetic evaluation of probands. Cox proportional hazards models were fitted to estimate the effect of genetic and cardiovascular factors on the onset of migraine, first stroke, and dementia. Competing risk regression models considered death as risk. RESULTS: Noncarriers (healthy controls from the same families without NOTCH3 mutations) and NOTCH3 mutation carriers had similar frequencies for all cardiovascular risk factors. Diabetes (SHR 2.74, 95\% CI 1.52-4.94) was associated with a younger age at onset of strokes among carriers. Additionally, a genotype-phenotype relationship was observed among C455R mutation carriers, with higher frequency of migraines (100\%), younger age at onset of migraine (median age 7\&nbsp;years, IQR 8) and strokes (median age 30.5\&nbsp;years, IQR 26). Moreover, fewer carriers of the R141C mutation exhibited migraines (20\%), and it was even lower than the frequency observed in the noncarrier group (44.8\%). CONCLUSIONS: This study characterizes extended family groups, allowing us a comparison in the genotype-phenotype. The results suggest a complex interplay of genetic and cardiovascular risk factors that may help explain the variability in the clinical presentation and severity of CADASIL.},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2020.117178},
	author = {Ospina, Carolina and Arboleda-Velasquez, Joseph F and Aguirre-Acevedo, Daniel Camilo and Zuluaga-Casta{\~n}o, Yesica and Velilla, Lina and Garcia, Gloria P and Quiroz, Yakeel T and Lopera, Francisco}
}
@article {1598062,
	title = {Transplantation of miPSC/mESC-derived retinal ganglion cells into healthy and glaucomatous retinas},
	journal = {Mol Ther Methods Clin Dev},
	volume = {21},
	year = {2021},
	month = {2021 Jun 11},
	pages = {180-198},
	abstract = {Optic neuropathies, including glaucoma, are a group of neurodegenerative diseases, characterized by the progressive loss of retinal ganglion cells (RGCs), leading to irreversible vision loss. While previous studies demonstrated the potential to replace RGCs with primary neurons from developing mouse retinas, their use is limited clinically. We demonstrate successful transplantation of mouse induced pluripotent stem cell (miPSC)/mouse embryonic stem cell (mESC)-derived RGCs into healthy and glaucomatous mouse retinas, at a success rate exceeding 65\% and a donor cell survival window of up to 12\&nbsp;months. Transplanted Thy1-GFP+ RGCs were able to polarize within the host retina and formed axonal processes that followed host axons along the retinal surface and entered the optic nerve head. RNA sequencing of donor RGCs re-isolated from host retinas at 24\&nbsp;h and 1\&nbsp;week post-transplantation showed upregulation of cellular pathways mediating axonal outgrowth, extension, and guidance. Additionally, we provide evidence of subtype-specific diversity within miPSC-derived RGCs prior to transplantation.},
	issn = {2329-0501},
	doi = {10.1016/j.omtm.2021.03.004},
	author = {Oswald, Julia and Kegeles, Evgenii and Minelli, Tomas and Volchkov, Pavel and Baranov, Petr}
}
@article {1598052,
	title = {V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity},
	journal = {J Virol},
	volume = {95},
	number = {16},
	year = {2021},
	month = {2021 07 26},
	pages = {e0061721},
	abstract = {The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.},
	issn = {1098-5514},
	doi = {10.1128/JVI.00617-21},
	author = {Ou, Junxian and Zhou, Zhonghua and Dai, Ruixue and Zhang, Jing and Zhao, Shan and Wu, Xiaowei and Lan, Wendong and Ren, Yi and Cui, Lilian and Lan, Qiaoshuai and Lu, Lu and Seto, Donald and Chodosh, James and Wu, Jianguo and Zhang, Gong and Zhang, Qiwei}
}
@article {1638560,
	title = {Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events},
	journal = {Signal Transduct Target Ther},
	volume = {7},
	number = {1},
	year = {2022},
	month = {2022 Apr 26},
	pages = {138},
	abstract = {The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, 18 core mutations of BA.1 (frequency \&gt;99\%) and 27 core mutations of BA.2 (nine more than BA.1) were identified, of which 15 are specific to Omicron. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations in BA.1 than BA.2, and BA.1 is phylogenetically closer to Alpha than other variants. Revertant mutations are found in some dominant mutations (frequency \&gt;95\%) in the BA.1. Most notably, multiple characteristic amino acid mutations in the Delta spike protein have been also identified in the "Deltacron"-like Omicron Variants isolated since November 11, 2021 in South Africa, which implies the recombination events occurring between the Omicron and Delta variants. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.},
	keywords = {Amino Acids, COVID-19, Genome, Viral, Humans, Mutation, Recombination, Genetic, SARS-CoV-2, Spike Glycoprotein, Coronavirus},
	issn = {2059-3635},
	doi = {10.1038/s41392-022-00992-2},
	author = {Ou, Junxian and Lan, Wendong and Wu, Xiaowei and Zhao, Tie and Duan, Biyan and Yang, Peipei and Ren, Yi and Quan, Lulu and Zhao, Wei and Seto, Donald and Chodosh, James and Luo, Zhen and Wu, Jianguo and Zhang, Qiwei}
}
@article {1351177,
	title = {Blink patterns and lid-contact times in dry-eye and normal subjects},
	journal = {Clin Ophthalmol},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {869-74},
	abstract = {PURPOSE: To classify blinks in dry eye and normal subjects into six subtypes, and to define the blink rate and duration within each type of blink, as well as the total lid-contact time/minute. MATERIALS AND METHODS: This was a single-centered, prospective, double-blind study of eleven dry-eye and ten normal subjects. Predefined subjects watched a video while blinks were recorded for 10 minutes. Partial blinks were classified by percentage closure of maximal palpebral fissure opening: 25\%, 50\%, 75\%. Complete blinks were characterized as full (\&gt;0 seconds), extended (\&gt;0.1 seconds), or superextended (\&gt;0.5 seconds). The mean duration of each type of blink was determined and standardized per minute as total lid-contact time. RESULTS: Total blinks observed were 4,990 (1,414 normal, 3,756 dry eye): 1,809 (50.59\%) partial and 1,767 (49.41\%) complete blinks among dry-eye subjects versus 741 (52.90\%) partial and 673 (47.60\%) complete blinks among normal subjects. Only superextended blinks of >=0.5-second duration were significantly more frequent in dry-eye subjects than normals (2.3\% versus 0.2\%, respectively; P=0.023). Total contact time was seven times higher in dry-eye subjects than normals (0.565 versus 0.080 seconds, respectively; P\&lt;0.001). Isolating only extended blinks (\&gt;0.1 second), the average contact time (seconds) was four times longer in dry-eye versus normal subjects (2.459 in dry eye, 0.575 in normals; P=0.003). Isolating only superextended blinks (\&gt;0.5 seconds), average contact time was also significantly different (7.134 in dry eye, 1.589 in normals; P\&lt;0.001). The contact rate for all full closures was 6.4 times longer in dry-eye (0.045 versus 0.007, P\&lt;0.001) than normal subjects. CONCLUSION: Dry-eye subjects spent 4.5\% of a minute with their eyes closed, while normal subjects spent 0.7\% of a minute with their eyes closed. Contact time might play a role in the visual function decay associated with increased blink rates.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S56783},
	author = {Ousler, George W and Abelson, Mark B and Johnston, Patrick R and Rodriguez, John and Lane, Keith and Smith, Lisa M}
}
@article {1195221,
	title = {Use of the Controlled Adverse Environment (CAE) in Clinical Research: A Review},
	journal = {Ophthalmol Ther},
	volume = {6},
	number = {2},
	year = {2017},
	month = {2017 Dec},
	pages = {263-276},
	abstract = {The many internal and external factors that contribute to the pathophysiology of dry eye disease (DED) create a difficult milieu for its study and complicate its clinical diagnosis and treatment. The controlled adverse environment (CAE{\textregistered}) model has been developed to minimize the variability that arises from exogenous factors and to exacerbate the signs and symptoms of DED by stressing the ocular surface in a safe, standardized, controlled, and reproducible manner. By integrating sensitive, specific, and clinically relevant endpoints, the CAE has proven to be a unique and adaptable model for both identifying study-specific patient populations with modifiable signs and symptoms, and for tailoring the evaluation of interventions in clinical research studies.},
	issn = {2193-8245},
	doi = {10.1007/s40123-017-0110-x},
	author = {Ousler, George W and Rimmer, David and Smith, Lisa M and Abelson, Mark B}
}
@article {469051,
	title = {Optimizing Reading Tests for Dry Eye Disease.},
	journal = {Cornea},
	year = {2015},
	month = {2015 Jun 10},
	abstract = {PURPOSE: The aim of this study was to evaluate the visual function information obtained from multiple reading tests in a dry eye population.

METHODS: In this case-control, single-center clinical research center-based study, 15 subjects with dry eye (mean age 65 years) and 10 normal subjects (mean age 40 years) were included. The Standardized Mini-Mental Examination was given to assure that subjects had normal cognitive function. Reading tests were both sentence based (Radner reading acuity test, reading contrast sensitivity test at a fixed print size, and menu-reading test) and paragraph based (Wilkins test and International Reading Speed Texts [IReST]). Wilkins and IReST tests were slightly modified to increase difficulty and visual stress. The main outcome measures were cognitive function, fatigue, dry eye symptoms, reading acuity, reading rate, and blink rate.

RESULTS: Results showed significantly lower rates in all reading tests in subjects with dry eye than in normal subjects; in the age-matched subgroup, only the menu and contrast sensitivity tests lost significance. Fatigue was significantly related to the IReST test, both at normal and critical print sizes. Reflex tearing was monitored and shown to significantly decrease the reading rate. IReST scores were considered the baseline, and the percent change from one test to IReST was also used to differentiate dry eye and normal subjects. The blink rate, symptoms, and demographics were not significantly correlated with reading tests.

CONCLUSIONS: Reading is a relevant end point that differentiates dry eye and normal subjects. This study evaluated a variety of reading tests for relevance as a measurable assessment of visual function in dry eye disease.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000490},
	author = {Ousler, George W and Rodriguez, John D and Smith, Lisa M and Lane, Keith J and Heckley, Colleen and Angjeli, Endri and Abelson, Mark B}
}
@article {1430535,
	title = {The Utah Protocol for Postmortem Eye Phenotyping and Molecular Biochemical Analysis},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {4},
	year = {2019},
	month = {2019 Mar 01},
	pages = {1204-1212},
	abstract = {Purpose: Current understanding of local disease pathophysiology in AMD is limited. Analysis of the human disease-affected tissue is most informative, as gene expression, expressed quantitative trait loci, microenvironmental, and epigenetic changes can be tissue, cell type, and location specific. Development of a novel translational treatment and prevention strategies particularly for earlier forms of AMD are needed, although access to human ocular tissue analysis is challenging. We present a standardized protocol to study rapidly processed postmortem donor eyes for molecular biochemical and genomic studies. Methods: We partnered with the Utah Lions Eye Bank to obtain donor human eyes, blood, and vitreous, within 6 hours postmortem. Phenotypic analysis was performed using spectral-domain optical coherence tomography (SD-OCT) and color fundus photography. Macular and extramacular tissues were immediately isolated, and the neural retina and retinal pigment epithelium/choroid from each specimen were separated and preserved. Ocular disease phenotype was analyzed using clinically relevant grading criteria by a group of four ophthalmologists incorporating data from SD-OCT retinal images, fundus photographs, and medical records. Results: The use of multimodal imaging leads to greater resolution of retinal pathology, allowing greater phenotypic rigor for both interobserver phenotype and known clinical diagnoses. Further, our analysis resulted in excellent quality RNA, which demonstrated appropriate tissue segregation. Conclusions: The Utah protocol is a standardized methodology for analysis of disease mechanisms in AMD. It uniquely allows for simultaneous rigorous phenotypic, molecular biochemical, and genomic analysis of both systemic and local tissues. This better enables the development of disease biomarkers and therapeutic interventions.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-24254},
	author = {Owen, Leah A and Shakoor, Akbar and Morgan, Denise J and Hejazi, Andre A and McEntire, M Wade and Brown, Jared J and Farrer, Lindsay A and Kim, Ivana and Vitale, Albert and Deangelis, Margaret M}
}
@article {1351178,
	title = {FLT1 genetic variation predisposes to neovascular AMD in ethnically diverse populations and alters systemic FLT1 expression},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {6},
	year = {2014},
	month = {2014 May 08},
	pages = {3543-54},
	abstract = {PURPOSE: Current understanding of the genetic risk factors for age-related macular degeneration (AMD) is not sufficiently predictive of the clinical course. The VEGF pathway is a key therapeutic target for treatment of neovascular AMD; however, risk attributable to genetic variation within pathway genes is unclear. We sought to identify single nucleotide polymorphisms (SNPs) associated with AMD within the VEGF pathway. METHODS: Using a tagSNP, direct sequencing and meta-analysis approach within four ethnically diverse cohorts, we identified genetic risk present in FLT1, though not within other VEGF pathway genes KDR, VEGFA, or VASH1. We used ChIP and ELISA in functional analysis. RESULTS: The FLT1 SNPs rs9943922, rs9508034, rs2281827, rs7324510, and rs9513115 were significantly associated with increased risk of neovascular AMD. Each association was more significant after meta-analysis than in any one of the four cohorts. All associations were novel, within noncoding regions of FLT1 that do not tag for coding variants in linkage disequilibrium. Analysis of soluble FLT1 demonstrated higher expression in unaffected individuals homozygous for the FLT1 risk alleles rs9943922 (P = 0.0086) and rs7324510 (P = 0.0057). In silico analysis suggests that these variants change predicted splice sites and RNA secondary structure, and have been identified in other neovascular pathologies. These data were supported further by murine chromatin immunoprecipitation demonstrating that FLT1 is a target of Nr2e3, a nuclear receptor gene implicated in regulating an AMD pathway. CONCLUSIONS: Although exact variant functions are not known, these data demonstrate relevancy across ethnically diverse genetic backgrounds within our study and, therefore, hold potential for global efficacy.},
	keywords = {Aged, Aged, 80 and over, Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Ethnic Groups, Female, Genetic Predisposition to Disease, Genotype, Greece, Humans, Immunoprecipitation, Macular Degeneration, Male, Mice, Mice, Inbred C57BL, Middle Aged, Polymorphism, Genetic, Prevalence, Republic of Korea, Retinal Neovascularization, Risk Factors, RNA, United Kingdom, United States, Vascular Endothelial Growth Factor Receptor-1},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14047},
	author = {Owen, Leah A and Morrison, Margaux A and Ahn, Jeeyun and Woo, Se Joon and Sato, Hajime and Robinson, Rosann and Morgan, Denise J and Zacharaki, Fani and Simeonova, Marina and Uehara, Hironori and Chakravarthy, Usha and Hogg, Ruth E and Ambati, Balamurali K and Kotoula, Maria and Baehr, Wolfgang and Haider, Neena B and Silvestri, Giuliana and Miller, Joan W and Tsironi, Evangelia E and Farrer, Lindsay A and Kim, Ivana K and Park, Kyu Hyung and Deangelis, Margaret M}
}
@article {1483620,
	title = {Effects of Omega-3 Supplementation on Exploratory Outcomes in the Dry Eye Assessment and Management Study},
	journal = {Ophthalmology},
	volume = {127},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {136-138},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.07.009},
	author = {Oydanich, Marko and Maguire, Maureen G and Pistilli, Maxwell and Hamrah, Pedram and Greiner, Jack V and Lin, Meng C and Asbell, Penny A and Dry Eye Assessment and Management Study Research Group}
}
@article {1598057,
	title = {Iris metastasis as the initial presentation of metastatic esophageal cancer diagnosed by fine needle aspiration biopsy: A case report},
	journal = {Medicine (Baltimore)},
	volume = {100},
	number = {22},
	year = {2021},
	month = {2021 Jun 04},
	pages = {e26232},
	abstract = {RATIONALE: Metastasis of neoplasms to the eye is quite uncommon. In this case report, we describe a patient where primary esophageal cancer was diagnosed by fine needle aspiration biopsy (FNAB) of an iris tumor. PATIENT CONCERNS: A 70-year-old male complained of redness and discomfort in the right eye. DIAGNOSIS AND INTERVENTIONS: The patient{\textquoteright}s right eye was diagnosed as idiopathic uveitis, and a topical steroid was administered. As vitreous opacities were observed even after topical therapy, oral prednisolone was administered. On slit-lamp examination of the right eye, an iris mass with neovascularization was seen in the anterior chamber. A metastatic tumor was suspected, and FNAB was performed. Histology revealed squamous cell carcinoma. Systemic workup revealed esophageal cancer with several metastases. Best-corrected visual acuity decreased to 20/400, and intraocular pressure was 40 mmHg in the right eye. Two iris tumors with neovascularization were present extending into the anterior chamber with posterior iris synechiae and 360 degree peripheral anterior synechiae. Intraocular pressure in the right eye was medically managed with hypotensive eye drops and oral acetazolamide. Iris metastases were treated with 40 Gray of radiation therapy and concurrent chemotherapy. OUTCOMES: The tumor regressed, but intraocular pressure was refractory to treatment because of 360 degree goniosynechial closure. The right eye lost light perception six months after treatment commenced, and the patient died 9 months after the onset of therapy due to multiple systemic metastases. LESSONS: This is a rare case of masquerade syndrome without systemic symptoms in which FNAB of an iris tumor led to a diagnosis of metastatic esophageal squamous cell carcinoma. Although the patient lost his sight due to uncontrollable ocular hypertension, systemic chemotherapy, and radiation therapy were initially effective in the treatment of the metastatic iris tumor. As the prognosis of patients with metastatic iris tumors is poor, it is important for ophthalmologists to consider such diagnoses and conduct systemic investigations when necessary.},
	keywords = {Acetazolamide, Administration, Oral, Aged, Anterior Chamber, Biopsy, Fine-Needle, Carbonic Anhydrase Inhibitors, Carcinoma, Squamous Cell, Chemoradiotherapy, Esophageal Neoplasms, Fatal Outcome, Humans, Intraocular Pressure, Iris, Iris Neoplasms, Male, Neoplasm Metastasis, Neovascularization, Pathologic, Ocular Hypertension, Visual Acuity},
	issn = {1536-5964},
	doi = {10.1097/MD.0000000000026232},
	author = {Ozawa, Hiroko and Usui, Yoshihiko and Takano, Yoji and Horiuchi, Naoki and Kuribayashi, Tohru and Kurihara, Toshihide and Smith, Lois E H and Tsubota, Kazuo and Tomita, Yohei}
}
@article {1667689,
	title = {Avascular Peripheral Retina in Infants},
	journal = {Turk J Ophthalmol},
	volume = {53},
	number = {1},
	year = {2023},
	month = {2023 Feb 24},
	pages = {44-57},
	abstract = {Avascular peripheral retina in an infant is a common characteristic of numerous pediatric retinal vascular disorders and often presents a diagnostic challenge to the clinician. In this review, key features of each disease in the differential diagnosis, from retinopathy of prematurity, familial exudative vitreoretinopathy, Coats disease, incontinentia pigmenti, Norrie disease, and persistent fetal vasculature, to other rare hematologic conditions and telomere disorders, will be discussed by expert ophthalmologists in the field.},
	keywords = {Child, Diagnosis, Differential, Humans, Infant, Infant, Newborn, Ophthalmologists, Rare Diseases, Retina, Retinal Diseases},
	issn = {2149-8709},
	doi = {10.4274/tjo.galenos.2022.76436},
	author = {{\"O}zdek, {\c S}eng{\"u}l and {\"O}zdemir Zeydanl{\i}, Ece and Baumal, Caroline and Hoyek, Sandra and Patel, Nimesh and Berrocal, Audina and Lopez-Ca{\~n}izares, Ashley and Al-Khersan, Hasenin and Kusaka, Shunji and Mano, Fukutaro and Jalali, Subhadra and Lepore, Domenico and Akar, Solmaz}
}
@article {1511506,
	title = {Preliminary effects of treating the half of high latent hyperopia on refractive and visual results of femtosecond laser-assisted in situ keratomileusis in subjects with hyperopia},
	journal = {Int Ophthalmol},
	volume = {40},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {2361-2369},
	abstract = {BACKGROUND: To evaluate the preliminary effects of treating the half of high latent hyperopia on refractive and visual outcomes of femtosecond laser-assisted in situ keratomileusis (LASIK) in young subjects with hyperopia. METHODS: This non-randomized comparative study includes 120 eyes of 60 subjects who underwent femtosecond LASIK to correct hyperopia. Group 1 (n = 60) includes subjects with <= 1D algebraic difference (DRSE) between cycloplegic (CRSE) and manifest (MRSE) refraction spherical equivalents and was treated by entering manifest refraction values. Group 2 includes subjects with \&gt; 1D DRSE and was treated by entering the mean manifest and cycloplegic refraction values. Refractive and subjective outcomes obtained at the 1-, 3-, and 6-month postoperative visits were compared. RESULTS: The mean age of the subjects was 26.2 {\textpm} 3.5 and 26.2 {\textpm} 5.2\&nbsp;years for Group 1 and Group 2, respectively. The male-to-female ratios were 10/10 in both groups. Demographic values of the groups were similar (p \&gt; 0.05). Preoperative MRSE values were similar (p = 0.924), while CRSE and DRSE values were significantly higher in Group 2 (p \&lt; 0.001). At the 1- and 3-month postoperative visits, MRSE was higher and uncorrected distance visual acuity (UDVA) was lower in Group 2 (p \&lt; 0.001). Subjective visual parameters and quality of vision scores were also worse in Group 2 during these visits (p \&lt; 0.001); however, at the 6-month visit, all outcomes for Group 2 improved, and MRSE, UDVA, some subjective visual parameters, and quality of vision scores became similar between groups (p \&gt; 0.05). CONCLUSION: At the 6-month visit after treating the half of \&gt; 1D latent hyperopia with femtosecond LASIK, refractive and visual outcomes like MRSE, UDVA, subjective visual parameters, and quality of vision scores become similar to those obtained in <= 1D latent hyperopia.},
	issn = {1573-2630},
	doi = {10.1007/s10792-020-01421-5},
	author = {Ozulken, Kemal and Ilhan, Cagri and Yuksel, Erdem and Mumcuoglu, Tarkan}
}
@article {1059791,
	title = {AAV-ID: A Rapid and Robust Assay for Batch-to-Batch Consistency Evaluation of AAV Preparations},
	journal = {Mol Ther},
	volume = {25},
	number = {6},
	year = {2017},
	month = {2017 Jun 07},
	pages = {1375-1386},
	abstract = {Adeno-associated virus (AAV) vectors are promising clinical candidates for therapeutic gene transfer, and a number of AAV-based drugs may emerge on the market over the coming years. To insure the consistency in efficacy and safety of any drug vial that reaches the patient, regulatory agencies require extensive characterization of the final product. Identity is a key characteristic of a therapeutic product, as it ensures its proper labeling and batch-to-batch consistency. Currently, there is no facile, fast, and robust characterization assay enabling to probe the identity of AAV products at the protein level. Here, we investigated whether the thermostability of AAV particles could inform us on the composition of vector preparations. AAV-ID, an assay based on differential scanning fluorimetry (DSF), was evaluated in two AAV research laboratories for specificity, sensitivity, and reproducibility, for six different serotypes (AAV1, 2, 5, 6.2, 8, and 9), using 67 randomly selected AAV preparations. In addition to enabling discrimination of AAV serotypes based on their melting temperatures, the obtained fluorescent fingerprints also provided information on sample homogeneity, particle concentration, and buffer composition. Our data support the use of AAV-ID as a reproducible, fast, and low-cost method to ensure batch-to-batch consistency in manufacturing facilities and academic laboratories.},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2017.04.001},
	author = {Pacouret, Simon and Bouzelha, Mohammed and Shelke, Rajani and Andres-Mateos, Eva and Xiao, Ru and Maurer, Anna and Mevel, Mathieu and Turunen, Heikki and Barungi, Trisha and Penaud-Budloo, Magalie and Broucque, Fr{\'e}d{\'e}ric and Blouin, V{\'e}ronique and Moullier, Philippe and Ayuso, Eduard and Vandenberghe, Luk H}
}
@article {1762016,
	title = {Impact of refresher training on the outcomes of trachomatous trichiasis surgery},
	journal = {Br J Ophthalmol},
	year = {2023},
	month = {2023 Sep 29},
	abstract = {BACKGROUND/AIMS: Trachomatous trichiasis (TT) is a severe consequence of chronic inflammation/conjunctival scarring resulting from trachoma, the leading infectious cause of blindness worldwide. Our prospective cohort study evaluated the effectiveness of refresher training (RT) for experienced surgeons (1-22 years) on the outcomes of upper lid (UL) TT surgery in rural Ethiopia. METHODS: Patients undergoing UL TT surgery in at least one eye by a participating surgeon were included. Patients were split into two cohorts: patients enrolled prior to (C1) and after (C2) RT. RT consisted of a 1-week programme with practice on a HEAD START mannequin and supportive supervision in live surgery by expert trainers. Data were collected at preoperative enrolment, and at 6-month and 12-month follow-up visits. The primary outcome was development of postoperative TT (PTT). A series of multivariate generalised estimating equations were fit to model PTT involving potential covariates of interest. RESULTS: A total of 261 eyes contributed by 173 patients were studied between 2017 and 2019. By 1-year postoperatively, 37/128 eyes (28.9\%) in C1 and 22/133 eyes (16.5\%) in C2 had developed PTT (p=0.03). Other than surgeon RT participation, no factors studied were associated with differences in PTT. CONCLUSION: Our results indicate a significant reduction in the risk of PTT after experienced surgeons{\textquoteright} participation in RT as compared with eyes receiving surgery before RT. This observation suggests a significant potential benefit of the RT with HEAD START mannequin practice and supportive supervision during surgery, and suggests RT may be a valuable strategy to improve surgical outcomes.},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-322497},
	author = {Pak, Clara and Hall, Nathan and Bekele, Demissie Tadesse and Kollmann, K H Martin and Tadele, Tesfaye and Tekle-Haimanot, Redda and Taye, Tarik and Qureshi, Babar and Yalew, Wubante and Gower, Emily W and Kempen, John H}
}
@article {1688241,
	title = {Haptic Erosion Following Sutureless Scleral-fixated Intraocular Lens Placement},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {333-337},
	abstract = {PURPOSE: To describe the clinical features and visual outcomes of eyes with conjunctival haptic erosion after sutureless intrascleral (SIS) fixated intraocular lens (IOL) placement. DESIGN: Retrospective case series. SUBJECTS: Patients experiencing haptic erosion after SIS fixation between January 1, 2013, and March 1,\&nbsp;2022. METHODS: A multicenter, multisurgeon, retrospective review. MAIN OUTCOME MEASURES: Clinical features, visual outcomes, and treatment options following haptic erosions after SIS fixation. RESULTS: Nineteen eyes with haptic erosion were identified. The mean age at initial SIS fixation was 64 {\textpm} 12 years (range, 38-81 years). There were 5 (26\%) eyes with a history of conjunctiva involving ocular surgery, including scleral buckle surgery and tube shunt surgery. Trocar-assisted fixation was performed in 15 (79\%) eyes, whereas needle fixation was used in 4 (21\%) eyes. Eighteen (95\%) sets of haptics were flanged with a low temperature cautery. Seventeen (90\%) sets of haptics were externalized superiorly and inferiorly, and 2 (10\%) sets of haptics were externalized nasally and temporally. Haptics were covered by conjunctiva in 14 (74\%) eyes and by scleral flap in 5 (26\%) eyes. All patients experienced a single haptic erosion, of which 8 (43\%) were located superiorly, 9 (47\%) inferiorly, and 2 (10\%) temporally. The mean interval between the initial SIS fixation and haptic erosion was 278 {\textpm} 437 days. After correction of the erosion, 18 (95\%) eyes had a stable IOL at the last follow-up, with no recurrence of haptic erosion. In this series, there were no cases of endophthalmitis. CONCLUSIONS: Haptic erosion is a notable complication after SIS fixated IOL surgery but may be repaired with favorable visual outcomes. Careful evaluation of the conjunctiva should be considered before the surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Adult, Aged, Aged, 80 and over, Haptic Technology, Humans, Lens Implantation, Intraocular, Lenses, Intraocular, Middle Aged, Retrospective Studies, Sclera},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.10.015},
	author = {Pakravan, Parastou and Patel, Veshesh and Chau, Viet and Rohowetz, Landon and Lai, James and Fan, Kenneth C and Al-Khersan, Hasenin and Melo, Isabela M and Muni, Rajeev H and Tsao, Sean W and Kaplan, Richard and Jung, Jesse J and Hoyek, Sandra and Patel, Nimesh A and Kuriyan, Ajay E and Laura, Diana M and Mantopoulos, Dimosthenis and Syed, Zeba A and Yannuzzi, Nicolas A}
}
@article {1466897,
	title = {Transient Mitomycin C-treatment of human corneal epithelial cells and fibroblasts alters cell migration, cytokine secretion, and matrix accumulation},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 Sep 25},
	pages = {13905},
	abstract = {A single application of Mitomycin C (MMC) is used clinically in ophthalmology to reduce scarring and enhance wound resolution after surgery. Here we show in vitro that a 3-hour MMC treatment of primary and telomerase immortalized human corneal limbal epithelial (HCLE) cells impacts their migration and adhesion. Transient MMC treatment induces HCLE expression of senescence associated secretory factors, cytokine secretion, and deposition of laminin 332 for several days. Transient MMC treatment also reduces migration and deposition of transforming growth factor-β1 (TGFβ1)-stimulated collagen by corneal fibroblasts. Using conditioned media from control and MMC treated cells, we demonstrate that factors secreted by MMC-treated corneal epithelial cells attenuate collagen deposition by HCFs whereas those secreted by MMC-treated HCFs do not. These studies are the first to probe the roles played by corneal epithelial cells in reducing collagen deposition by corneal fibroblasts in response to MMC.},
	issn = {2045-2322},
	doi = {10.1038/s41598-019-50307-9},
	author = {Pal-Ghosh, Sonali and Tadvalkar, Gauri and Lieberman, Verna Rose and Guo, Xiaoqing and Zieske, James D and Hutcheon, Audrey and Stepp, Mary Ann}
}
@article {541261,
	title = {Topical Mitomycin-C enhances subbasal nerve regeneration and reduces erosion frequency in the debridement wounded mouse cornea.},
	journal = {Exp Eye Res},
	year = {2015},
	month = {2015 Aug 30},
	abstract = {Corneal epithelial basement membrane dystrophies and superficial injuries caused by scratches can lead to recurrent corneal erosion syndrome (RCES). Patients and animals with reduced corneal sensory nerve innervation can also develop recurrent erosions. Multiple wild-type mouse strains will spontaneously develop recurrent corneal erosions after single 1.5 mm debridement wounds. Here we show that this wound is accompanied by an increase in corneal epithelial cell proliferation after wound closure but without a commensurate increase in corneal epithelial thickness. We investigated whether excess corneal epithelial cell proliferation contributes to erosion formation. We found that topical application of Mitomycin C (MMC), a drug used clinically to improve healing after glaucoma and refractive surgery, reduces erosion frequency, enhances subbasal axon density to levels seen in unwounded corneas, and prevents excess epithelial cell proliferation after debridement wounding. These results suggest that topically applied MMC, which successfully reduces corneal haze and scarring after PRK, may also function to enhance subbasal nerve regeneration and epithelial adhesion when used to treat RCES.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2015.08.023},
	author = {Pal-Ghosh, Sonali and Pajoohesh-Ganji, Ahdeah and Tadvalkar, Gauri and Kyne, Briana M and Guo, Xiaoqing and Zieske, James D and Stepp, Mary Ann}
}
@article {1363171,
	title = {A novel approach to the management of a progressive Descemet membrane tear in a patient with keratoglobus and acute hydrops},
	journal = {Cornea},
	volume = {32},
	number = {3},
	year = {2013},
	month = {2013 Mar},
	pages = {355-8},
	abstract = {PURPOSE: To report a case of corneal hydrops in a patient with keratoglobus that was managed with endothelial keratoplasty to achieve corneal stability and prevent a limbus-to-limbus tear in Descemet membrane. METHODS: A 30-year-old man with keratoglobus presented with corneal hydrops in his left eye resulting from a central vertical tear in Descemet membrane. His other eye had been previously treated with penetrating keratoplasty using a large graft (an 11-mm donor graft to a 10-mm recipient bed) because of a limbus-to-limbus tear in Descemet membrane without resolution of his edema. An attempt to approximate the edges of the Descemet tear in the left eye by an intracameral air injection failed, and the tear continued to progress peripherally. An endothelial keratoplasty button with anchoring sutures was placed over the Descemet tear because of excessive localized edema. RESULTS: One month after insertion of the sutured endothelial keratoplasty button, the edema had resolved, and 1 year later, the tear remains sealed. The patient{\textquoteright}s visual acuity improved from counting fingers at 1 foot to 20/100. CONCLUSIONS: Reconstitution of the posterior corneal surface in keratoglobus-induced hydrops can be achieved with endothelial keratoplasty over the Descemet tear. Preventing progression of a central Descemet tear is essential to bypass the need for a large-diameter penetrating keratoplasty graft and its complications in a young patient with a history of bilateral corneal hydrops.},
	keywords = {Acute Disease, Adult, Air, Cornea, Corneal Diseases, Corneal Edema, Corneal Topography, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Disease Progression, Endotamponade, Eye Abnormalities, Humans, Male, Reoperation, Rupture, Spontaneous, Suture Techniques, Visual Acuity},
	issn = {1536-4798},
	doi = {10.1097/ICO.0b013e31825cea80},
	author = {Palioura, Sotiria and Chodosh, James and Pineda, Roberto}
}
@article {931131,
	title = {Outcomes of Descemet Stripping Endothelial Keratoplasty Using Eye Bank-Prepared Preloaded Grafts.},
	journal = {Cornea},
	volume = {36},
	number = {1},
	year = {2017},
	pages = {21-25},
	abstract = {PURPOSE: To evaluate the feasibility of Descemet stripping endothelial keratoplasty using grafts preloaded by an eye bank in a commercially available insertion device. METHODS: In this retrospective case series, a series of 35 eyes in 34 consecutive patients who underwent Descemet stripping endothelial keratoplasty for Fuchs endothelial dystrophy or previously failed full-thickness grafts at a single tertiary care center from March 2013 to March 2014 was included. The donor tissue had undergone pre-lamellar dissection, trephination, and loading into EndoGlide Ultrathin inserters at the Lions Eye Institute for Transplant and Research (Tampa, FL) and was shipped overnight in Optisol GS to the surgeon (K.C.). Surgery was performed within 24 hours from tissue preparation and loading by the eye bank. Donor and recipient characteristics, endothelial cell density (ECD), best-corrected visual acuity, and central corneal thickness were recorded. The main outcome measures were intraoperative and postoperative complications and ECD loss at 3, 6, and 12 months. RESULTS: One primary graft failure (2.8\%), 2 rebubblings (5.7\%), and 1 graft rejection (2.8\%) occurred. Mean preoperative donor ECD was 2821 {\textpm} 199 cells/mm. Six months postoperatively, the mean endothelial cell loss was 25.3\% {\textpm} 17.2\% (n = 32), which remained stable at 1 year (31.5\% {\textpm} 17.9\%, n = 32). Mean best-corrected visual acuity improved from 20/100 preoperatively to 20/25 at a mean follow-up of 1 year (n = 32). Mean central corneal thickness was reduced from 711 {\textpm} 110 μm to 638 {\textpm} 66 μm at the last follow-up visit. CONCLUSIONS: Donor graft tissue preloaded by an eye bank can be used successfully for endothelial keratoplasty. Preloading reduces intraoperative tissue manipulation.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001039},
	author = {Palioura, Sotiria and Colby, Kathryn}
}
@article {1363172,
	title = {The Boston keratoprosthesis type I in mucous membrane pemphigoid},
	journal = {Cornea},
	volume = {32},
	number = {7},
	year = {2013},
	month = {2013 Jul},
	pages = {956-61},
	abstract = {PURPOSE: To evaluate the use of the Boston keratoprosthesis type I implantation in patients with mucous membrane pemphigoid (MMP). METHODS: Retrospective review of 8 eyes of 8 patients with severe ocular surface disease and corneal blindness as a result of MMP who underwent Boston keratoprosthesis type I implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000, through December 31, 2009. The main outcome measures were best-corrected visual acuity, keratoprosthesis retention, and postoperative complications. RESULTS: The mean age of patients was 71.3 years (range, 55-94 years), and the mean duration of their disease preoperatively was 6.1 years (range, 1.7-11.4 years). Visual acuity after the surgery improved to 20/200 or better in 6 eyes (75\%) and to 20/40 or better in 3 eyes (37.5\%). Only 1 of 6 eyes (16.7\%) was able to maintain visual acuity of 20/200 or better over a mean follow-up period of 3.2 years. Five of the 8 Boston keratoprosthesis type I devices (62.5\%) extruded or had to be replaced during a mean follow-up time of 1.7 {\textpm} 1.7 years. Loss of vision to worse than 20/200 during the follow-up period occurred because of keratoprosthesis type I extrusion, end-stage glaucoma, and retinal or choroidal detachment. CONCLUSIONS: The clinical outcomes of Boston keratoprosthesis type I implantation in MMP are guarded and, as judged from the literature, less favorable than those with the Boston keratoprosthesis type II for the same disease.},
	keywords = {Aged, Aged, 80 and over, Anesthesia, General, Conjunctival Diseases, Corneal Diseases, Female, Graft Survival, Humans, Male, Middle Aged, Pemphigoid, Benign Mucous Membrane, Postoperative Complications, Prostheses and Implants, Prosthesis Implantation, Retrospective Studies, Treatment Outcome, Visual Acuity},
	issn = {1536-4798},
	doi = {10.1097/ICO.0b013e318286fd73},
	author = {Palioura, Sotiria and Kim, Bryan and Dohlman, Claes H and Chodosh, James}
}
@article {1598065,
	title = {Characterization of the Spectrum of Ophthalmic Changes in Patients With Alagille Syndrome},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {62},
	number = {7},
	year = {2021},
	month = {2021 Jun 01},
	pages = {27},
	abstract = {Purpose: The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome. Methods: We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings. Results: Cardiovascular abnormalities were found in 83\% of all cases (of those, 74\% had cardiac murmur), whereas 61\% had a positive history of hepatobiliary issues, and musculoskeletal anomalies were present in 61\% of all patients. Dysmorphic facies were present in 16 patients, with a broad forehead being the most frequent feature. Ocular symptoms were found in 91\%, with peripheral vision loss being the most frequent complaint. Median (range) Snellen visual acuity of all eyes was 20/25 (20/20 to hand motion [HM]). Anterior segment abnormalities were present in 74\% of the patients; of those, posterior embryotoxon was the most frequent finding. Abnormalities of the optic disc were found in 52\%, and peripheral retinal abnormalities were the most frequent ocular finding in this series, found in 96\% of all patients. Fifteen JAG1 mutations were identified in 16 individuals; of those, 6 were novel. Conclusions: This study reports a cohort of patients with Alagille syndrome in which peripheral chorioretinal changes were more frequent than posterior embryotoxon, the most frequent ocular finding according to a number of previous studies. We propose that these peripheral chorioretinal changes are a new hallmark to help diagnose this syndrome.},
	issn = {1552-5783},
	doi = {10.1167/iovs.62.7.27},
	author = {da Palma, Mariana Matioli and Igelman, Austin D and Ku, Cristy and Burr, Amanda and You, Jia Yue and Place, Emily M and Wang, Nan-Kai and Oh, Jin Kyun and Branham, Kari E and Zhang, Xinxin and Ahn, Jeeyun and Gorin, Michael B and Lam, Byron L and Ronquillo, Cecinio C and Bernstein, Paul S and Nagiel, Aaron and Huckfeldt, Rachel and Cabrera, Michelle T and Kelly, John P and Bakall, Benjamin and Iannaccone, Alessandro and Hufnagel, Robert B and Zein, Wadih M and Koenekoop, Robert K and Birch, David G and Yang, Paul and Fahim, Abigail T and Pennesi, Mark E}
}
@article {1333935,
	title = {Measuring the time course of selection during visual search},
	journal = {Atten Percept Psychophys},
	year = {2018},
	month = {2018 Sep 21},
	abstract = {In visual search tasks, observers can guide their attention towards items in the visual field that share features with the target item. In this series of studies, we examined the time course of guidance toward a subset of items that have the same color as the target item. Landolt Cs were placed on 16 colored disks. Fifteen distractor Cs had gaps facing up or down while one target C had a gap facing left or right. Observers searched for the target C and reported which side contained the gap as quickly as possible. In the absence of other information, observers must search at random through the Cs. However, during the trial, the disks changed colors. Twelve disks were now of one color and four disks were of another color. Observers knew that the target C would always be in the smaller color set. The experimental question was how quickly observers could guide their attention to the smaller color set. Results indicate that observers could not make instantaneous use of color information to guide the search, even when they knew which two colors would be appearing on every trial. In each study, it took participants 200-300 ms to fully utilize the color information once presented. Control studies replicated the finding with more saturated colors and with colored C stimuli (rather than Cs on colored disks). We conclude that segregation of a display by color for the purposes of guidance takes 200-300 ms to fully develop.},
	issn = {1943-393X},
	doi = {10.3758/s13414-018-1596-6},
	author = {Palmer, Evan M and Van Wert, Michael J and Horowitz, Todd S and Wolfe, Jeremy M}
}
@article {1364522,
	title = {Comparative genomics of enterococci: variation in Enterococcus faecalis, clade structure in E. faecium, and defining characteristics of E. gallinarum and E. casseliflavus},
	journal = {MBio},
	volume = {3},
	number = {1},
	year = {2012},
	month = {2012},
	pages = {e00318-11},
	abstract = {The enterococci are Gram-positive lactic acid bacteria that inhabit the gastrointestinal tracts of diverse hosts. However, Enterococcus faecium and E. faecalis have emerged as leading causes of multidrug-resistant hospital-acquired infections. The mechanism by which a well-adapted commensal evolved into a hospital pathogen is poorly understood. In this study, we examined high-quality draft genome data for evidence of key events in the evolution of the leading causes of enterococcal infections, including E. faecalis, E. faecium, E. casseliflavus, and E. gallinarum. We characterized two clades within what is currently classified as E. faecium and identified traits characteristic of each, including variation in operons for cell wall carbohydrate and putative capsule biosynthesis. We examined the extent of recombination between the two E. faecium clades and identified two strains with mosaic genomes. We determined the underlying genetics for the defining characteristics of the motile enterococci E. casseliflavus and E. gallinarum. Further, we identified species-specific traits that could be used to advance the detection of medically relevant enterococci and their identification to the species level.},
	keywords = {Alleles, Bacterial Proteins, Cell Wall, Enterococcus, Evolution, Molecular, Genetic Loci, Genetic Variation, Genome, Bacterial, Gram-Positive Bacterial Infections, Host-Pathogen Interactions, Phylogeny, Polysaccharides, Bacterial, Species Specificity},
	issn = {2150-7511},
	doi = {10.1128/mBio.00318-11},
	author = {Palmer, Kelli L and Godfrey, Paul and Griggs, Allison and Kos, Veronica N and Zucker, Jeremy and Desjardins, Christopher and Cerqueira, Gustavo and Gevers, Dirk and Walker, Suzanne and Wortman, Jennifer and Feldgarden, Michael and Haas, Brian and Birren, Bruce and Gilmore, Michael S}
}
@article {1608608,
	title = {Visual perception supported by verbal mediation in an individual with cerebral visual impairment (CVI)},
	journal = {Neuropsychologia},
	volume = {160},
	year = {2021},
	month = {2021 09 17},
	pages = {107982},
	abstract = {Cerebral visual impairment (CVI) often presents with deficits associated with higher order visual processing. We report a case of an individual with CVI who uses a verbal mediation strategy to perceive and interact with his visual surroundings. Visual perceptual performance was assessed using a virtual reality based visual search task combined with eye tracking. Functional magnetic resonance imaging (fMRI) was employed to identify the neural correlates associated with this strategy. We found that when using verbal mediation, the individual could readily detect and track the target within the visual scene which was associated with robust activation within a network of occipito-parieto-temporal visual cortical areas. In contrast, when not using verbal mediation, the individual was completely unable to perform the task, and this was associated with dramatically reduced visual cortical activation. This unique compensatory strategy may be related to the individual{\textquoteright}s use of verbal working memory for the purposes of understanding complex visual information.},
	keywords = {Adolescent, Brain Mapping, Cognition, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Vision Disorders, Visual Perception},
	issn = {1873-3514},
	doi = {10.1016/j.neuropsychologia.2021.107982},
	author = {Pamir, Zahide and Bauer, Corinna M and Bennett, Christopher R and Kran, Barry S and Merabet, Lotfi B}
}
@article {1658669,
	title = {Preparing participants for the use of the tongue visual sensory substitution device},
	journal = {Disabil Rehabil Assist Technol},
	volume = {17},
	number = {8},
	year = {2022},
	month = {2022 Nov},
	pages = {888-896},
	abstract = {PURPOSE: Visual sensory substitution devices (SSDs) convey visual information to a blind person through another sensory modality. Using a visual SSD in various daily activities requires training prior to use the device independently. Yet, there is limited literature about procedures and outcomes of the training conducted for preparing users for practical use of SSDs in daily activities. METHODS: We trained 29 blind adults (9 with congenital and 20 with acquired blindness) in the use of a commercially available electro-tactile SSD, BrainPort. We describe a structured training protocol adapted from the previous studies, responses of participants, and we present retrospective qualitative data on the progress of participants during the training. RESULTS: The length of the training was not a critical factor in reaching an advanced stage. Though performance in the first two sessions seems to be a good indicator of participants{\textquoteright} ability to progress in the training protocol, there are large individual differences in how far and how fast each participant can progress in the training protocol. There are differences between congenital blind users and those blinded later in life. CONCLUSIONS: The information on the training progression would be of interest to researchers preparing studies, and to eye care professionals, who may advise patients to use SSDs.IMPLICATIONS FOR REHABILITATIONThere are large individual differences in how far and how fast each participant can learn to use a visual-to-tactile sensory substitution device for a variety of tasks.Recognition is mainly achieved through top-down processing with prior knowledge about the possible responses. Therefore, the generalizability is still questionable.Users develop different strategies in order to succeed in training tasks.},
	keywords = {Adult, Blindness, Humans, Retrospective Studies, Tongue, Touch, Visually Impaired Persons},
	issn = {1748-3115},
	doi = {10.1080/17483107.2020.1821102},
	author = {Pamir, Zahide and Jung, Jae-Hyun and Peli, Eli}
}
@article {1490450,
	title = {Poor resolution at the back of the tongue is the bottleneck for spatial pattern recognition},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Feb 12},
	pages = {2435},
	abstract = {Spatial patterns presented on the tongue using electro-tactile sensory substitution devices (SSDs) have been suggested to be recognized better by tracing the pattern with the tip of the tongue. We examined if the functional benefit of tracing is overcoming the poor sensitivity or low spatial resolution at the back of the tongue or alternatively compensating for limited information processing capacity by fixating on a segment of the spatial pattern at a time. Using a commercially available SSD, the BrainPort, we compared letter recognition performance in three presentation modes; tracing, static, and drawing. Stimulation intensity was either constant or increased from the tip to the back of the tongue to partially compensate for the decreasing sensitivity. Recognition was significantly better for tracing, compared to static and drawing conditions. Confusion analyses showed that letters were confused based on their characteristics presented near the tip in static and drawing conditions. The results suggest that recognition performance is limited by the poor spatial resolution at the back of the tongue, and tracing seems to be an effective strategy to overcome this. Compensating for limited information processing capacity or poor sensitivity by drawing or increasing intensity at the back, respectively, does not improve the performance.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-59102-3},
	author = {Pamir, Zahide and Canoluk, M Umut and Jung, Jae-Hyun and Peli, Eli}
}
@article {1016116,
	title = {Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c},
	journal = {Nat Biotechnol},
	volume = {35},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {264-272},
	abstract = {Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G\&gt;A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G\&gt;A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90\% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.},
	issn = {1546-1696},
	doi = {10.1038/nbt.3801},
	author = {Pan, Bifeng and Askew, Charles and Galvin, Alice and Heman-Ackah, Selena and Asai, Yukako and Indzhykulian, Artur A and Jodelka, Francine M and Hastings, Michelle L and Lentz, Jennifer J and Vandenberghe, Luk H and Holt, Jeffrey R and G{\'e}l{\'e}oc, Gwena{\"e}lle S}
}
@article {1490457,
	title = {Author Correction: Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Feb 06},
	pages = {2395},
	abstract = {An amendment to this paper has been published and can be accessed via a link at the top of the paper.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-59304-9},
	author = {Pan, Peipei and Weisenberger, Daniel J and Zheng, Siyu and Wolf, Marie and Hwang, David G and Rose-Nussbaumer, Jennifer R and Jurkunas, Ula V and Chan, Matilda F}
}
@article {1732686,
	title = {IGFBPL1 is a master driver of microglia homeostasis and resolution of neuroinflammation in glaucoma and brain tauopathy},
	journal = {Cell Rep},
	volume = {42},
	number = {8},
	year = {2023},
	month = {2023 Aug 29},
	pages = {112889},
	abstract = {Microglia shift toward an inflammatory phenotype during aging that is thought to exacerbate age-related neurodegeneration. The molecular and cellular signals that resolve neuroinflammation post-injury are largely undefined. Here, we exploit systems genetics methods based on the extended BXD murine reference family and identify IGFBPL1 as an upstream cis-regulator of microglia-specific genes to switch off inflammation. IGFBPL1 is expressed by mouse and human microglia, and higher levels of its expression resolve lipopolysaccharide-induced neuroinflammation by resetting the transcriptome signature back to a homeostatic state via IGF1R signaling. Conversely, IGFBPL1 deficiency or selective deletion of IGF1R in microglia shifts these cells to an inflammatory landscape and induces early manifestation of brain tauopathy and retinal neurodegeneration. Therapeutic administration of IGFBPL1 drives pro-homeostatic microglia and prevents glaucomatous neurodegeneration and vision loss in mice. These results identify IGFBPL1 as a master driver of the counter-inflammatory microglial modulator that presents an endogenous resolution of neuroinflammation to prevent neurodegeneration in eye and brain.},
	keywords = {Animals, Brain, Homeostasis, Humans, Inflammation, Insulin-Like Growth Factor Binding Proteins, Mice, Microglia, Neuroinflammatory Diseases, Tauopathies, Tumor Suppressor Proteins},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2023.112889},
	author = {Pan, Li and Cho, Kin-Sang and Wei, Xin and Xu, Fuyi and Lennikov, Anton and Hu, Guangan and Tang, Jing and Guo, Shuai and Chen, Julie and Kriukov, Emil and Kyle, Robert and Elzaridi, Farris and Jiang, Shuhong and Dromel, Pierre A and Young, Michael and Baranov, Petr and Do, Chi-Wai and Williams, Robert W and Chen, Jianzhu and Lu, Lu and Chen, Dong Feng}
}
@article {742286,
	title = {Serum molecular signature for proliferative diabetic retinopathy in Saudi patients with type 2 diabetes.},
	journal = {Mol Vis},
	volume = {22},
	year = {2016},
	month = {2016},
	pages = {636-45},
	abstract = {PURPOSE: The risk of vision loss from proliferative diabetic retinopathy (PDR) can be reduced with timely detection and treatment. We aimed to identify serum molecular signatures that might help in the early detection of PDR in patients with diabetes. METHODS: A total of 40 patients with diabetes were recruited at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, 20 with extensive PDR and 20 with mild non-proliferative diabetic retinopathy (NPDR). The two groups were matched in age, gender, and known duration of diabetes. We examined the whole genome transcriptome of blood samples from the patients using RNA sequencing. We built a model using a support vector machine (SVM) approach to identify gene combinations that can classify the two groups. RESULTS: Differentially expressed genes were calculated from a total of 25,500 genes. Six genes (CCDC144NL, DYX1C1, KCNH3, LOC100506476, LOC285847, and ZNF80) were selected from the top 26 differentially expressed genes, and a combinatorial molecular signature was built based on the expression of the six genes. The mean area under receiver operating characteristic (ROC) curve was 0.978 in the cross validation. The corresponding sensitivity and specificity were 91.7\% and 91.5\%, respectively. CONCLUSIONS: Our preliminary study defined a combinatorial molecular signature that may be useful as a potential biomarker for early detection of proliferative diabetic retinopathy in patients with diabetes. A larger-scale study with an independent cohort of samples is necessary to validate and expand these findings.},
	issn = {1090-0535},
	author = {Pan, Jianbo and Liu, Sheng and Farkas, Michael and Consugar, Mark and Zack, Donald J and Kozak, Igor and Arevalo, J Fernando and Pierce, Eric and Qian, Jiang and Al Kahtani, Eman}
}
@article {1417570,
	title = {Elevated Intraocular Pressure in a Young Man With a History of Laser-Assisted In Situ Keratomileusis},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Jan 03},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.5430},
	author = {Pan, Billy X and Margeta, Milica A}
}
@article {1347442,
	title = {Rapid Construction of a Replication-Competent Infectious Clone of Human Adenovirus Type 14 by Gibson Assembly},
	journal = {Viruses},
	volume = {10},
	number = {10},
	year = {2018},
	month = {2018 Oct 18},
	abstract = {In 1955, Human adenovirus type 14 (HAdV-B14p) was firstly identified in a military trainee diagnosed as acute respiratory disease (ARD) in the Netherlands. Fifty years later, a genomic variant, HAdV-B14p1, re-emerged in the U.S. and caused large and fatal ARD outbreaks. Subsequently, more and more ARD outbreaks occurred in Canada, the UK, Ireland, and China, in both military and civil settings. To generate a tool for the efficient characterization of this new genomic variant, a full-length infectious genomic clone of HAdV-B14 was successfully constructed using one-step Gibson Assembly method in this study. Firstly, the full genome of HAdV-B14p1 strain GZ01, the first HAdV-B14 isolate in China, was assembled into pBR322 plasmid by Gibson Assembly. The pBRAdV14 plasmid, generated by Gibson Assembly, was analyzed and verified by PCR, restriction enzymes digestion and the sequencing. Secondly, viruses were rescued from pBRAdV14-transfected A549 cells. The integrity of the rescued viruses was identified by restriction enzyme analysis. The complete sequence of the infectious clone was further sequenced. No mutation was found in the infectious clone during the construction when compared with the parental virus and pBR322 sequences. The direct immunofluorescence assay indicated the expression of the hexon protein. Finally, typical virions were observed; the one-step growth curves further showed that the DNA replication and viral reproduction efficiency of pBRAd14 derived viruses was similar with that of wild-type HAdV-B14 strain. The successful construction of the replication-competent infectious clone of pBRAdV14 facilitates the development of vaccine and antiviral drugs against HAdV-B14, as well as provides a novel strategy for rapid construction of infectious viral clones for other large-genome DNA viruses.},
	issn = {1999-4915},
	doi = {10.3390/v10100568},
	author = {Pan, Haibin and Yan, Yuqian and Zhang, Jing and Zhao, Shan and Feng, Liqiang and Ou, Junxian and Cao, Na and Li, Min and Zhao, Wei and Wan, Chengsong and Ismail, Ashrafali M and Rajaiya, Jaya and Chodosh, James and Zhang, Qiwei}
}
@article {1474205,
	title = {Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 Nov 08},
	pages = {16385},
	abstract = {Homeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix (ECM) is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples from FECD patients. We discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. More specifically, miR-199B is extensively hypermethylated and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Furthermore, we find that miR-199b-5p directly and negatively regulates Snai1 and ZEB1, two zinc finger transcription factors that lead to increased ECM deposition in FECD. Taken together, these findings suggest a novel epigenetic regulatory mechanism of matrix protein production by corneal endothelial cells in which miR-199B hypermethylation leads to miR-199b-5p downregulation and thereby the increased expression of its target genes, including Snai1 and ZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.},
	issn = {2045-2322},
	doi = {10.1038/s41598-019-52727-z},
	author = {Pan, Peipei and Weisenberger, Daniel J and Zheng, Siyu and Wolf, Marie and Hwang, David G and Rose-Nussbaumer, Jennifer R and Jurkunas, Ula V and Chan, Matilda F}
}
@article {1549003,
	title = {The Rising Interest in Canthoplasty: An Analysis of Online Search Trends},
	journal = {J Craniofac Surg},
	year = {2020},
	month = {2020 Nov 23},
	abstract = {Canthoplasty as a cosmetic procedure appears to be on the rise in the West. Online search query data offers a powerful tool for analyzing population trends, including changes in patient interest in surgical procedures. Cosmetic surgeons can utilize the internet to increase patient education and interest, as well as to provide information and address misinformation. In this study we sought to verify the increase in cosmetic canthoplasty, for the first time, through analysis of Internet search data, and to establish trends in the interest of Internet users for cosmetic canthoplasty. These trends were subsequently compared with trends in literature publication to establish whether there is a correlation between patient and surgeon interest in the procedure.},
	issn = {1536-3732},
	doi = {10.1097/SCS.0000000000007272},
	author = {Panayi, Adriana C and Wu, Mengfan and Liu, Qinxin and Haug, Valentin and Yu, Zhen}
}
@article {705106,
	title = {A novel endothelial-derived anti-inflammatory activity significantly inhibits spontaneous choroidal neovascularisation in a mouse model.},
	journal = {Vasc Cell},
	volume = {8},
	year = {2016},
	month = {2016},
	pages = {2},
	abstract = {BACKGROUND: Endothelial cells (EC) grown on collagen particles inhibit intimal hyperplasia in animal models when applied perivascularly, and this effect appears to be, at least in part, the result of EC-derived soluble factors that suppress local vascular inflammation. To elucidate the molecular basis of the therapeutic effects of EC grown on collagen particles, the anti-inflammatory activity of conditioned medium from these cells was characterized. METHODS: Human aortic EC (HAEC) and, for chromatin immunoprecipitation assays, human umbilical vein EC (HUVEC) were treated with tumor necrosis factor alpha (TNFα) in the presence of conditioned medium generated by HAEC grown on collagen particles (ECPCM), and the anti-inflammatory effects were evaluated by analysing the expression of the inflammation-related adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1). The therapeutic activity of ECPCM was studied using the mouse strain JR5558, which develops spontaneous choroidal neovascularisation (CNV) lesions driven by local inflammation. RESULTS: ECPCM significantly suppressed TNFα-induced expression of E-selectin and VCAM-1. ECPCM did not affect the mRNA stability of the two genes, but suppressed TNFα-induced binding of the p65 subunit of NF-kB transcription factor to E-selectin and VCAM-1 promoters. In vivo, systemic ECPCM treatment significantly reduced the CNV area and the recruitment of activated macrophages to the lesions. Characterization of the molecule responsible for the anti-inflammatory activity in ECPCM indicates that it is unlikely to be a protein and that it is not any of the better characterized EC-derived anti-inflammatory molecules. CONCLUSIONS: Medium conditioned by HAEC grown on collagen particles exhibits significant anti-inflammatory activity via inhibition of genes that mediate inflammatory responses in EC.},
	issn = {2045-824X},
	doi = {10.1186/s13221-016-0036-4},
	author = {Paneghetti, Laura and Ng, Yin-Shan Eric}
}
@article {314171,
	title = {Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration.},
	journal = {Pathology},
	volume = {46},
	number = {5},
	year = {2014},
	month = {2014 Aug},
	pages = {416-23},
	abstract = {Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF). A soluble isoform of Nrp1 (sNrp1) has not been described in the mouse. Our goal was to examine the expression of mouse sNrp1 during liver development and regeneration.sNrp1 was cloned from mouse liver. The expression of sNrp1 and VEGF was examined in mouse liver during post-natal development and regeneration using northern blot, western blot, in situ hybridisation, and immunohistochemical analyses. HGF/NRP1 binding was examined in vitro.A novel 588-amino acid sNrp1 isoform was found to contain the ligand binding regions of Nrp1. The adult liver expressed more sNrp1 than full-length Nrp1. In vivo, hepatocytes constitutively expressed VEGF and sNrp1 in the quiescent state. sNrp1 was highly up-regulated at P20, a time point coinciding with a plateau in liver and body weights. Following hepatectomy, endogenous levels of sNrp1 decreased during the rapid growth phase, and VEGF levels were highest just prior to and during the angiogenic phase. sNrp1 levels again rose 5-10 days post-hepatectomy, presumably to control regeneration. HGF protein bound NRP1 and binding was competed with sNRP1.We cloned a novel mouse sNrp1 isoform from liver and provide evidence that this endogenous angiogenesis inhibitor may regulate VEGF or HGF bioavailability during normal physiological growth and development as well as during liver regeneration.},
	issn = {1465-3931},
	doi = {10.1097/PAT.0000000000000121},
	author = {Panigrahy, Dipak and Adini, Irit and Mamluk, Roni and Levonyak, Nicholas and Bruns, Christiane J and D{\textquoteright}Amore, Patricia A and Klagsbrun, Michael and Bielenberg, Diane R}
}
@article {1363173,
	title = {Choroiditis and choroidal neovascularization in acute disseminated encephalomyelitis},
	journal = {Retin Cases Brief Rep},
	volume = {7},
	number = {1},
	year = {2013},
	month = {2013 Winter},
	pages = {89-90},
	abstract = {PURPOSE: To present a case with bilateral choroidal neovascularization (CNV) secondary to acute disseminated encephalomyelitis-associated choroiditis requiring immunomodulatory therapy for prevention of recurrence. METHODS: The clinical course of a patient diagnosed with acute disseminated encephalomyelitis, who developed bilateral choroiditis at the time of his neurologic diagnosis and bilateral CNV 6 years later, is reviewed. PATIENT: A 57-year-old man developed CNV in both eyes, 6 years after the initial diagnosis of acute disseminated encephalomyelitis-associated choroiditis. The patient was initially treated successfully with intravitreal bevacizumab injections and oral prednisone, but CNV recurred with steroid tapering. Mycophenolate mofetil was initiated as steroid-sparing immunomodulatory therapy. RESULTS: There was no CNV recurrence for 1.5 years without the need for additional antiangiogenic therapy. CONCLUSION: To our best knowledge, this is the first report of choroiditis and secondary CNV associated with acute disseminated encephalomyelitis. In cases of recurrent CNV associated with choroiditis, systemic therapy should be strongly considered in conjunction with antiangiogenic therapy. The recurrence of CNV with tapering of oral steroids and the remission of CNV with steroid-sparing immunomodulatory therapy support the role of ongoing inflammation in the pathogenesis.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0b013e31826f08e8},
	author = {Panou, Nikol and Kim, Ivana K and Sobrin, Lucia}
}
@article {1452976,
	title = {Aflibercept: A review of its effect on the treatment of exudative age-related macular degeneration},
	journal = {Eur J Ophthalmol},
	volume = {29},
	number = {4},
	year = {2019},
	month = {2019 Jul},
	pages = {368-378},
	abstract = {Considerable improvement has been achieved in the way in which exudative age-related macular degeneration is conventionally treated and in the associated visual outcomes and prognosis, thanks to the agents with effects against vascular endothelial growth factor (anti-VEGF). By comparison to earlier treatment approaches that involved the use of lasers, the anti-VEGF agents have made it possible to accomplish more positive visual and anatomical outcomes in cases of exudative age-related macular degeneration. Indeed, owing to their positive effects, anti-VEGF agents have quickly come to be considered the gold standard for the treatment of wet age-related macular degeneration. Aflibercept, the most recently approved intravitreally administered anti-VEGF, seems to mark another milestone in the treatment of wet age-related macular degeneration. This anti-VEGF agent presents a series of singular pharmacodynamic and pharmacokinetic attributes that provide it a number of biological benefits in relation to the treatment of choroidal neovascularization compared to other agents. These attributes include high level of affinity for the VEGF-A factor, an intravitreal half-life of great length, as well as the ability to serve as an antagonist for other growth factors besides VEGF. The impact of Aflibercept on the manner in which exudative age-related macular degeneration is managed was demonstrated by thoroughly reviewing the related literature. The present review article highlights the pharmacology, pharmacokinetics, safety and effectiveness of this anti-VEGF agent as well as the landmark clinical studies that have been carried out to establish this drug as a gold standard in the therapy of neovascular age-related macular degeneration. In addition, studies regarding the outcomes and effectiveness of the various dosage regimens, either as monotherapy or in combination with other agents, are also reviewed.},
	issn = {1724-6016},
	doi = {10.1177/1120672119832432},
	author = {Papadopoulos, Zois}
}
@article {1483605,
	title = {Neovascular age-related macular degeneration and its association with Alzheimer{\textquoteright}s disease},
	journal = {Curr Aging Sci},
	year = {2020},
	month = {2020 Jan 29},
	abstract = {In developed countries, people of advanced age go permanently blind most often due to age-related macular degeneration, while at global level, this disease is the third major cause of blindness, after cataract and glaucoma, according to the World Health Organisation. The number of individuals believed to suffer from the disease throughout the world has been approximated at 50 million. Age-related macular degeneration is classified as non-neovascular (dry, non-exudative) and neovascular (wet, exudative). The exudative form is less common than the non-exudative as it accounts for approximately 10 percent of the cases of the disease. However, it can be much more aggressive and results in a rapid and severe loss of central vision. Similarly with age-related macular degeneration, Alzheimer{\textquoteright}s disease is a late-onset, neurodegenerative disease affecting millions of people worldwide. Both of them are associated with age and share several features, including the presence of extracellular abnormal deposits associated with neuronal degeneration, drusen, and plaques, respectively. The present review article highlights the pathogenesis, the clinical features and the imaging modalities used for the diagnosis of neovascular age-related macular degeneration. A thorough overview of the effectiveness of anti-VEGF agents as well as of other treatment modalities that have either lost favour or are rarely used is provided in detail. Additionally, the common histologic, immunologic, and pathogenetic features of Alzheimer{\textquoteright}s disease and age-related macular degeneration are discussed in depth.},
	issn = {1874-6128},
	doi = {10.2174/1874609813666200129161833},
	author = {Papadopoulos, Zois}
}
@article {1532382,
	title = {Recent Developments in the Treatment of Wet Age-related Macular Degeneration},
	journal = {Curr Med Sci},
	volume = {40},
	number = {5},
	year = {2020},
	month = {2020 Oct},
	pages = {851-857},
	abstract = {Age-related macular degeneration (AMD) is the most common cause of irreversible blindness and visual impairment in individuals over the age of 50 years in western societies. More than 25 million people currently suffer from this illness in the world, with an additional 500 000 every year, approximately. It is a multifactorial ocular disease that affects the maculae due to a late-onset progressive neurodegeneration and dysfunction of photoreceptors and retinal pigment epithelium (RPE). There are many subtypes of AMD but basically two broad forms: the nonneovascular (dry, nonexudative) and neovascular (wet, exudative). Exudative AMD is the less common form (about 15\%) but tends to progress more rapidly. At the moment, wet AMD is treated primarily on the basis of anti-vascular endothelial growth factor (VEGF) agents, which have led to massive improvement in the prognosis of the disease since they were first introduced. This article focuses on the latest treatment approaches to neovascular AMD. An extensive literature review was performed in order to illustrate the effectiveness of current and future anti-VEGF agents as well as the landmark clinical studies that have been carried out to establish these drugs as a gold standard in the therapy of wet AMD.},
	issn = {2523-899X},
	doi = {10.1007/s11596-020-2253-6},
	author = {Papadopoulos, Zois}
}
@article {1603875,
	title = {Central neurotoxicity induced by trastuzumab emtansine (T-DM1): a case report},
	journal = {Anticancer Drugs},
	volume = {32},
	number = {10},
	year = {2021},
	month = {2021 11 01},
	pages = {1146-1149},
	abstract = {Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (Her2) - targeted antibody-drug conjugate that is approved for patients previously treated with trastuzumab and a taxane for Her2-positive advanced breast cancer and those who have progressed within 6 months of completion of adjuvant chemotherapy, as well as for patients with residual invasive Her2-positive disease after the completion of adjuvant chemotherapy. Peripheral neuropathy is a common adverse event; however, ocular events have also been described. With the current report we present the case of a 67-year old woman who developed transient grade 2-3 blurred vision after the first T-DM1 infusion, which was complicated with grade 2 diplopia causing vertigo after the second infusion. After extended investigation, this symptomatology was attributed to central neurotoxicity, and gradually resolved after T-DM1 discontinuation.},
	issn = {1473-5741},
	doi = {10.1097/CAD.0000000000001117},
	author = {Papageorgiou, Georgios I and Symeonidis, David G and Tsakatikas, Sergios A and Liatsos, Alexandros D and Douglas, Konstantinos Aa and Douglas, Vivian P and Moschos, Marilita M and Kosmas, Christos}
}
@article {313271,
	title = {Medical management of Alternaria keratitis with endophthalmitis in a patient with a corneal graft},
	journal = {Clin Exp Ophthalmol},
	volume = {42},
	number = {5},
	year = {2014},
	month = {2014 Jul},
	pages = {496-7},
	keywords = {Administration, Oral, Administration, Topical, Adult, Alternaria, Alternariosis, Antifungal Agents, Corneal Transplantation, Corneal Ulcer, Drug Therapy, Combination, Endophthalmitis, Eye Infections, Fungal, Glucocorticoids, Humans, Male, Prednisolone, Voriconazole},
	issn = {1442-9071},
	doi = {10.1111/ceo.12238},
	author = {Papakostas, Thanos D and Kohanim, Sahar and Skondra, Dimitra and Lo, Kristine and Chodosh, James}
}
@article {341786,
	title = {Idiopathic dacryoadenitis mimicking a primary intraocular tumour in a young girl.},
	journal = {Clin Experiment Ophthalmol},
	volume = {42},
	number = {8},
	year = {2014},
	month = {2014 Nov},
	pages = {785-8},
	issn = {1442-9071},
	doi = {10.1111/ceo.12305},
	author = {Papakostas, Thanos D and Jakobiec, Frederick A and Mantagos, Jason and Rashid, Alia and Fay, Aaron and Vavvas, Demetrios G}
}
@article {1363174,
	title = {Endogenous panophthalmitis with orbital cellulitis secondary to Escherichia coli},
	journal = {Clin Exp Ophthalmol},
	volume = {41},
	number = {7},
	year = {2013},
	month = {2013 Sep-Oct},
	pages = {716-8},
	keywords = {Aged, Blepharoptosis, Escherichia coli Infections, Exophthalmos, Eye Enucleation, Eye Infections, Bacterial, Female, Humans, Magnetic Resonance Imaging, Ophthalmoplegia, Orbital Cellulitis, Panophthalmitis, Tomography, X-Ray Computed},
	issn = {1442-9071},
	doi = {10.1111/ceo.12094},
	author = {Papakostas, Thanos D and Lee, N Grace and Lefebvre, Daniel R and Barshak, Miriam B and Freitag, Suzanne K}
}
@article {303871,
	title = {Prosthetic replacement of the ocular surface ecosystem as treatment for ocular surface disease in patients with a history of stevens-johnson syndrome/toxic epidermal necrolysis.},
	journal = {Ophthalmology},
	volume = {122},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {248-53},
	abstract = {PURPOSE: To report the visual outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in patients with ocular surface disease related to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). DESIGN: Retrospective cohort study. SUBJECTS: We included 86 patients (167 eyes) with history of SJS/TEN who underwent PROSE treatment from January 1, 2006, to January 1, 2011. METHODS: Etiology, previous interventions, change in visual acuity, change in visual function, and duration of follow-up are reported. Paired t test and Friedman test with Dunn{\textquoteright}s post hoc test for multiple comparisons were used for statistical analysis. MAIN OUTCOME MEASURES: Visual acuity at last follow-up and visual function based on the National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) at 6 months. RESULTS: We treated 35 males and 51 females with a history of SJS/TENS; median age was 36 years. The most common reported etiologies for SJS/TENS were antibiotics (n\&nbsp;= 25), ibuprofen (n\&nbsp;= 15), and lamotrigine (n\&nbsp;=\&nbsp;11). The median visual acuity at the initial visit was 20/60 (range, 20/400-20/25; 0.48 logarithm of the minimum angle of resolution [logMAR]), and the visual acuity at completion of customization was 20/25 (range, 20/200-20/20; 0.096 logMAR; P \&lt; 0.001), with no decline in median acuity at the end of follow-up. Median duration of follow-up was 16 months. There was a significant improvement in the visual function of the patients based on the NEI VFQ-25 questionnaire (mean of 48 points at baseline vs. mean of 72 points at 6 months; P\&nbsp;\&lt;\&nbsp;0.001). In addition, there was also an improvement in the self-reported general health of the patients (mean of 57 points at baseline vs. mean of 65 points at 6 months; P \&lt; 0.01). CONCLUSIONS: In a large cohort of patients with chronic ocular surface disease related to SJS/TEN, PROSE\&nbsp;treatment offers sustained and significant large improvement in visual function and acuity.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.08.015},
	author = {Papakostas, Thanos D and Le, Hong-Gam and Chodosh, James and Jacobs, Deborah S}
}
@article {1363175,
	title = {Teaching video neuroimages: pulsatile proptosis},
	journal = {Neurology},
	volume = {81},
	number = {21},
	year = {2013},
	month = {2013 Nov 19},
	pages = {e160},
	abstract = {A 44-year-old man with neurofibromatosis type 1 had been aware that his right eye pulsated. His visual acuity was 20/15 in both eyes and his intraocular pressures were normal. He had 4 mm of right exophthalmos and there was pulse-synchronous pulsation of the right eye (video on the Neurology{\textregistered} Web site at www.neurology.org). No bruit was heard. Lisch nodules were present on both irides. CT showed a large osseous defect of the greater wing of the right sphenoid bone. The differential diagnosis of pulsatile proptosis includes absence of the sphenoid wing in patients with neurofibromatosis 1,(1) carotid-cavernous fistula, orbital roof fractures, and arteriovenous malformations.(2.)},
	keywords = {Adult, Exophthalmos, Humans, Male, Neurofibromatosis 1, Neuroimaging, Neurology, Sphenoid Bone, Tomography, X-Ray Computed},
	issn = {1526-632X},
	doi = {10.1212/01.wnl.0000436066.35760.24},
	author = {Papakostas, Thanos D and Lessell, Simmons}
}
@article {541246,
	title = {Unusual focal remnant of the tunica vasculosa lentis.},
	journal = {Clin Experiment Ophthalmol},
	year = {2015},
	month = {2015 Sep 8},
	issn = {1442-9071},
	doi = {10.1111/ceo.12642},
	author = {Papakostas, Thanos D and Jakobiec, Frederick A and Stagner, Anna M and Vavvas, Demetrios}
}
@article {280856,
	title = {Reactivation of thyroid associated orbitopathy following trauma with intraorbital foreign body.},
	journal = {Orbit},
	volume = {34},
	number = {1},
	year = {2015},
	month = {2015 Feb},
	pages = {6-9},
	abstract = {A 63-year-old female with mild, bilateral, stable thyroid-associated orbitopathy sustained trauma resulting in glass foreign bodies embedded on the left ocular surface and left lateral orbital extraconal and intraconal space. After 2 orbitotomies including a failed attempt to remove the intraconal foreign body and poor response to oral steroids, she developed severe, progressive left periorbital edema and 9 mm of relative proptosis. Serial, post-operative imaging demonstrated worsening inflammatory changes along the surgical tract, which slowly improved over several months, with simultaneously worsening proptosis and enlargement of the left inferior and medial rectus muscles consistent with worsening thyroid orbitopathy. She subsequently underwent unilateral 3-wall orbital decompression with improvement in her symptoms. Periorbital trauma with orbital foreign bodies and related surgical trauma may result in reactivation of thyroid-associated orbitopathy.},
	issn = {1744-5108},
	doi = {10.3109/01676830.2014.950301},
	author = {Papakostas, Thanos D and Lee, Nahyoung Grace and Callahan, Alison B and Freitag, Suzanne K}
}
@article {1732656,
	title = {Incidence of and Risk Factors for Cataract in Anterior Uveitis},
	journal = {Am J Ophthalmol},
	volume = {254},
	year = {2023},
	month = {2023 Oct},
	pages = {221-232},
	abstract = {PURPOSE: To estimate the incidence/risk factors for cataract in noninfectious anterior uveitis. DESIGN: Retrospective multicenter cohort study (6 US tertiary uveitis sites, 1978-2010). METHODS: Data were harvested by trained expert reviewers, using protocol-driven review of experts{\textquoteright} charts. We studied cataract incidence-newly reduced visual acuity worse than 20/40 attributed to cataract; or incident cataract surgery-in 3923 eyes of 2567 patients with anterior uveitis. RESULTS: Cataract developed in 507 eyes (54/1000 eye-years, 95\% CI 49-59). Time-updated risk factors associated with cataract included older age (>=65 vs \&lt;18 years: adjusted hazard ratio [aHR] 5.04, 95\% CI 3.04-8.33), higher anterior chamber cell grade (P(trend)=0.001), prior incisional glaucoma surgery (aHR 1.86, 95\% CI 1.10-3.14), band keratopathy (aHR 2.23, 95\% CI 1.47-3.37), posterior synechiae (aHR 3.71, 95\% CI 2.83-4.87), and elevated intraocular pressure >=30 vs 6-20 mm Hg (aHR 2.57, 95\% CI 1.38-4.77). Primary acute (aHR 0.59, 95\% CI 0.30-1.15) and recurrent acute (aHR 0.74, 95\% CI 0.55-0.98) had lower cataract risk than chronic anterior uveitis. Higher-dose prednisolone acetate 1\%-equivalent use (>=2 drops/day) was associated with \&gt;2-fold higher cataract risk in eyes with anterior chamber cell grades 0.5+ or lower but was not associated with higher cataract risk in the presence of anterior chamber cells of grade 1+ or higher. CONCLUSIONS: Cataract complicates anterior uveitis in \~{}5.4/100 eye-years. Several fixed and modifiable risk factors were identified, yielding a point system to guide cataract risk minimization. Topical corticosteroids only were associated with increased cataract risk when anterior chamber cells were absent or minimally present, suggesting their use to treat active inflammation (which itself is cataractogenic) does not cause a net increase in cataract incidence.},
	keywords = {Acute Disease, Cataract, Cohort Studies, Humans, Incidence, Retrospective Studies, Risk Factors, Uveitis, Uveitis, Anterior},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.06.021},
	author = {Papaliodis, George N and Rosner, Bernard A and Dreger, Kurt A and Fitzgerald, Tonetta D and Artornsombudh, Pichaporn and Kothari, Srishti and Gangaputra, Sapna S and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Bhatt, Nirali P and Foster, C Stephen and Jabs, Douglas A and Pak, Clara M and Ying, Gui-Shuang and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study Research Group}
}
@article {397841,
	title = {Ipilimumab-induced Ocular and Orbital Inflammation-A Case Series and Review of the Literature.},
	journal = {Ocul Immunol Inflamm},
	volume = {24},
	number = {2},
	year = {2016},
	month = {2016 Apr},
	pages = {140-6},
	abstract = {PURPOSE: Ipilimumab, a monoclonal antibody directed against the immune protein cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side effects called "immune-related adverse events" (IRAE). Although ophthalmic involvement is rare, we report 7 cases of eye and orbit complications related to ipilimumab therapy. METHODS: We performed a retrospective review of patients with metastatic melanoma who developed ipilimumab-related ocular or orbital inflammation who were seen at our institutions. RESULTS: Seven patients were identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had peripheral ulcerative keratitis. Four patients developed inflammation after the second ipilimumab infusion, 2 after the third infusion and 1 after the first infusion. All 4 patients with orbital inflammation were treated with systemic corticosteroids. Two patients with uveitis were treated with topical steroids, but were also treated with systemic corticosteroids for other IRAE, including colitis and hypophysitis. The patient with keratitis was treated with topical corticosteroids alone with resolution of inflammation. All 7 patients discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor progression. Five of 7 patients had tumor progression on ipilimumab therapy. CONCLUSIONS: Ocular and orbital inflammation may occur in patients with metastatic melanoma receiving ipilimumab, is frequently accompanied by other IRAEs, and resolves with corticosteroid treatment, often leaving no long-term sequelae.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2014.1001858},
	author = {Papavasileiou, Evangelia and Prasad, Sashank and Freitag, Suzanne K and Sobrin, Lucia and Lobo, Ann-Marie}
}
@article {439611,
	title = {SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CONVALESCENT PHASE OF TREATED SARCOID CHOROIDAL GRANULOMAS.},
	journal = {Retin Cases Brief Rep},
	volume = {10},
	number = {1},
	year = {2016},
	month = {2016 Winter},
	pages = {32-6},
	abstract = {PURPOSE: To report swept-source optical coherence tomography findings of sarcoid choroidal granulomas in the posttreatment convalescent stage of disease. PATIENTS/METHODS: The authors retrospectively reviewed charts from patients with sarcoid-related choroidal granulomas and recorded pertinent examination and imaging findings. Swept-source optical coherence tomography was performed using the DRI 3D-OCT-1 Atlantis (Topcon) over the areas of previous choroidal granulomas after the patients had been treated. RESULTS: Three patients with sarcoid choroidal granulomas were imaged with swept-source optical coherence tomography. Findings included loss or alteration of choroidal architecture, subretinal fibrosis, and outer retinal tubulations in the areas of the sarcoid granulomas after treatment. In one case with an associated choroidal neovascular membrane, there was also disruption of Bruch membrane and loss of normal choroidal vascular network in the area of the lesion. CONCLUSION: Swept-source optical coherence tomography demonstrated significant anatomical sequelae that persisted after treatment of sarcoid granulomas. To the best of the authors{\textquoteright} knowledge, this is the first report of outer retinal tubulations over healed sarcoid granulomas.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000156},
	author = {Papavasileiou, Evangelia and Miller, John B and Sobrin, Lucia}
}
@article {913511,
	title = {Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {255},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {509-517},
	abstract = {PURPOSE: Previous studies have yielded conflicting results regarding whether serum lipid levels are associated with retinal hard exudates in diabetic retinopathy. The majority of studies have assessed hard exudates only as a dichotomous trait (presence vs. absence) and included limited numbers of African Americans (AA). The purpose of this study was to determine if there are any associations between serum lipid levels and hard exudates in AA with type 2 diabetes (T2D).

METHODS: 890 AA participants with T2D were enrolled from 5 sites. Macular fundus photographs were graded by masked ophthalmologist investigators. Hard exudate areas were measured using a semi-automated algorithm and ImageJ software. Multivariate regression models were used to determine the association between serum lipid levels and (1) presence of hard exudate and (2) area of hard exudate.

RESULTS: Presence of hard exudates was associated with higher total cholesterol [(odds ratio (OR) = 1.08, 95~\% confidence interval (CI) 1.03-1.13, P = 0.001)] and higher low-density lipoprotein (LDL) cholesterol (OR = 1.08, 95~\% CI 1.03-1.14, P = 0.005) in models controlling for other risk factors. Hard exudate area was also associated with both higher total and LDL cholesterol levels (P = 0.04 and 0.01, respectively) in multivariate models controlling for other risk factors.

CONCLUSIONS: Higher total and LDL cholesterol were associated with the presence of hard exudates and a greater hard exudate area in AA with T2D. This information can be used to counsel diabetic patients regarding the importance of lipid control to decrease the risk of macular hard exudates.},
	issn = {1435-702X},
	doi = {10.1007/s00417-016-3493-9},
	author = {Papavasileiou, Evangelia and Davoudi, Samaneh and Roohipoor, Ramak and Cho, Heeyoon and Kudrimoti, Shreyas and Hancock, Heather and Wilson, James G and Andreoli, Christopher and Husain, Deeba and James, Maurice and Penman, Alan and Chen, Ching J and Sobrin, Lucia}
}
@article {397836,
	title = {Ocular ischemic syndrome presenting as retinal vasculitis in a patient with moyamoya syndrome.},
	journal = {Retin Cases Brief Rep},
	volume = {9},
	number = {2},
	year = {2015},
	month = {2015 Spring},
	pages = {170-2},
	abstract = {PURPOSE: To report a case of ocular ischemic syndrome presenting as retinal vasculitis in a patient with Moyamoya syndrome. METHODS: A retrospective chart review was conducted to record clinical data including fluorescein angiography, optical coherence tomography, and serologic testing. A review of the literature from 1969 to 2014 of ocular involvement in Moyamoya syndrome was performed. RESULTS: A 51-year-old woman with long history of bilateral retinal vasculitis and refractory cystoid macular edema was eventually diagnosed with Moyamoya syndrome after sustaining a perioperative cerebrovascular accident. Moyamoya syndrome has been associated in the literature with ocular ischemic syndrome, presenting with narrowed retinal arteries, dilated veins, and midperipheral retinal hemorrhages, but retinal vasculitis with cystoid macular edema has not been reported. CONCLUSION: Moyamoya-related ocular ischemic syndrome can present as retinal vascular leakage and macular edema. Ophthalmologists should be cognizant that signs of the disease may be first observed in the eye before manifestations in the cerebrovascular system.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000129},
	author = {Papavasileiou, Evangelia and Sobrin, Lucia and Papaliodis, George N}
}
@article {313116,
	title = {O-015 image guided bleomycin sclerotherapy for orbital lymphatic malformation.},
	journal = {J Neurointerv Surg},
	volume = {6 Suppl 1},
	year = {2014},
	month = {2014 Jul},
	pages = {A8-9},
	abstract = {INTRODUCTION: Orbital lymphatic malformations (OLMs) are a unique subset of head and neck low flow vascular malformations, located either in the periorbital region or in the closed orbital cavity. We discuss our experience of minimally invasive strategies of treatment using advanced imaging and Bleomycin sclerotherapy to effectively treat these malformations. MATERIALS AND METHODS: Between 2008 and 2013, we have treated 54 cases of orbital low flow vascular malformations including 22 cases of OLMs of which 16 were treated using Bleomycin. This retrospective analysis was performed from patient charts, operative reports, operative images, pre-operative, and post-operative MR imaging. Bleomycin was used for sclerotherapy in all the cases with a maximum dose per session of treatment limited to 15 mgs. DIRECT PUNCTURE SCLEROTHERAPY TECHNIQUE: OLMs target was determined using pre-procedure MR imaging and direct puncture either per-cutaneous or per-conjunctival was achieved using ultrasound or i-guide guidance. In most lymphatic fluid was drained else the position confirmed with constrast injection under fluoroscopy. Bleomycin was used either undiluted or in various concentrations mixed with saline, or contrast material and recently we favor the use of Bleofoam mixed with 25\% Human albumin and air. Microcystic LMs, were treated using gravity technique, the needle track was sealed with Surgiflo or Floseal. In cases of intra cystic or intra ocular haemorrhage with elevated orbital pressure, lateral canthotomy was performed to prevent permanent damage to vision and the contents of the orbit. Postoperatively, the patients recover in ICU and monitored for vision and orbital swelling. Bleomycin skin precautions were followed for 72 h in order to avoid skin hyperpigmentation. Optimal results were obtained at 6 to 8 weeks and assessed using follow-up MRI and ophthalmologic evaluation. RESULTS: The patient{\textquoteright}s age ranged from 1 to 45 years, with equal male to female ratio. Most cases (13/16) (80\%) presented non acutely while three patients (20\%) presented acutely with proptosis, visual disturbance and double vision due to haemorrhage within the malformation. Treatment completed in 14, one lost to follow up and the other is yet to be followed. The follow up period ranged from 6weeks to 6 months. 65\% (9/14) needed less than three procedures while the remaining five patients needed between 3-5 procedures. All patients had improvement in proptosis; vision either remained stable or improved; volume reduction of more than 80\% was noted in 57\% (8/14), while the remaining patients 43\% had volume reduction of 50-79\%. One patient had transient mydriasis post procedure that completely recovered at three months. Another developed haemorrhage within the malformation immediate post sclerotherapy requiring lateral canthotomy, drainage and redo sclerotherapy. None of our patients developed skin pigmentation or pulmonary complication related to bleomycin usage. CONCLUSION: Bleomycin sclerotherapy combined with appropriate image guidance for precise target localization is an effective and safe treatment for OLMs. Bleomycin is a preferred sclerosant as it induces minimal inflammation and post procedure swelling. Standard precautions must be instituted to prevent cutaneous pigmentation and pulmonary fibrosis. DISCLOSURES: S. Paramasivam: None. A. Fay: None. J. Fifi: None. A. Berenstein: None.},
	issn = {1759-8486},
	doi = {10.1136/neurintsurg-2014-011343.15},
	author = {Paramasivam, S and Fay, A and Fifi, J and Berenstein, A}
}
@article {1626095,
	title = {Impact of COVID-19 restrictions on corneal tissue donation and utilization rate - Time to bring reforms?},
	journal = {Indian J Ophthalmol},
	volume = {69},
	number = {12},
	year = {2021},
	month = {2021 Dec},
	pages = {3782-3784},
	keywords = {Cornea, Corneal Transplantation, COVID-19, Humans, SARS-CoV-2, Tissue and Organ Procurement, Tissue Donors},
	issn = {1998-3689},
	doi = {10.4103/ijo.IJO_2714_21},
	author = {Parekh, Mohit and Nathawat, Rakhi and Parihar, Jitendra Kumar Singh and Jhanji, Vishal and Sharma, Namrata}
}
@article {1709651,
	title = {DMEK surgical training: An instructional guide on various wet-lab methods},
	journal = {Surv Ophthalmol},
	volume = {68},
	number = {6},
	year = {2023},
	month = {2023 Nov-Dec},
	pages = {1129-1152},
	abstract = {Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet membrane and endothelium. DMEK offers significant advantages over other keratoplasty techniques, such as faster visual rehabilitation, better final visual acuity due to minimal optical interface effects, lower risk of allograft rejection, and less long-term dependence on topical steroids. Despite all its advantages, DMEK has been found to be more challenging than other corneal transplantation techniques, and its steep learning curve appears to be an obstacle to its widespread use and adoption by corneal surgeons worldwide. DMEK surgical training laboratories (wet labs) provide a window of opportunity for surgeons to learn, prepare, manipulate, and deliver these grafts in a risk-free environment. Wet labs are a significant learning tool, especially for those institutions that have limited tissue availability in their local centers. We provide a step-by-step guide for preparing DMEK grafts using different techniques on human and nonhuman models with instructional videos. This article should eventually help the trainees and the educators understand the requirements for performing DMEK and conducting a DMEK wet lab and develop their skills and interests from a wide variety of available techniques.},
	keywords = {Cornea, Corneal Diseases, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Humans, Laboratories},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2023.06.008},
	author = {Parekh, Mohit and Ruzza, Alessandro and Rovati, Marco and Tzamalis, Argyrios and Romano, Davide and Gupta, Nidhi and Vaddavalli, Pravin and Bhogal, Maninder and Jhanji, Vishal and Sawant, Onkar and Semeraro, Francesco and Ponzin, Diego and Jacob, Soosan and Dragnea, Diana Carmen and Rodriguez-Calvo-De-Mora, Marina and N{\'\i} Dhubhghaill, Sorcha and Fogla, Rajesh and Sharma, Namrata and Jurkunas, Ula V and Ferrari, Stefano and Romano, Vito}
}
@article {1635620,
	title = {Factors Affecting the Success Rate of Preloaded Descemet Membrane Endothelial Keratoplasty With Endothelium-Inward Technique: A Multicenter Clinical Study},
	journal = {Am J Ophthalmol},
	volume = {241},
	year = {2022},
	month = {2022 09},
	pages = {272-281},
	abstract = {PURPOSE: To evaluate factors affecting the outcomes of preloaded Descemet membrane endothelial keratoplasty (pl-DMEK) with endothelium-inward. DESIGN: Retrospective clinical case series and a comparative tissue preparation study. METHODS: Participants: Fifty-five donor tissues for ex vivo study and 147 eyes of 147 patients indicated with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy with or without cataract. INTERVENTION: Standardized DMEK peeling was performed with 9.5-mm-diameter trephination followed by second trephination for loading the graft (8.0-9.5 mm diameter). The tissues were manually preloaded with endothelium-inward and preserved for 4 days or shipped for transplantation. Live and dead assay and immunostaining was performed on ex vivo tissues. For the clinical study, the tissues were delivered using bimanual pull-through technique followed by air tamponade at all the centers. MAIN OUTCOME MEASURES: Tissue characteristics, donor and recipient factors, rebubbling rate, endothelial cell loss (ECL), and corrected distance visual acuity (CDVA) at 3, 6, and 12 months. RESULTS: At day 4, significant cell loss (P\&nbsp;=\&nbsp;.04) was observed in pl-DMEK with loss of biomarker expression seen in prestripped and pl-DMEK tissues. Rebubbling was observed in 40.24\% cases. Average ECL at 3, 6, and 12 months was 45.87\%, 40.98\%, and 47.54\%, respectively. CDVA improved significantly at 3 months postoperation (0.23 {\textpm} 0.37 logMAR) (P \&lt; .01) compared to the baseline (0.79 {\textpm} 0.61 logMAR). A significant association (P \&lt; .05) between graft diameter, preservation time, recipient gender, gender mismatch, and recipient age to rebubbling rate was observed. CONCLUSION: Graft loading to delivery time of pl-DMEK tissues in endothelium-inward fashion must be limited to 4 days after processing. Rebubbling rate and overall surgical outcomes following preloaded DMEK can be multifactorial and center-specific.},
	keywords = {Cell Count, Corneal Endothelial Cell Loss, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.03.009},
	author = {Parekh, Mohit and Pedrotti, Emilio and Viola, Pietro and Leon, Pia and Neri, Enrico and Bosio, Lorenzo and Bonacci, Erika and Ruzza, Alessandro and Kaye, Stephen B and Ponzin, Diego and Ferrari, Stefano and Romano, Vito}
}
@article {1645453,
	title = {DMEK graft: One size does not fit all},
	journal = {Acta Ophthalmol},
	volume = {101},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {e14-e25},
	abstract = {Descemet membrane endothelial keratoplasty (DMEK) is a popular procedure for the treatment of corneal endothelial diseases mainly targeting Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). Although DMEK has multiple advantages, it is challenging in terms of graft preparation and delivery. One of the crucial factors of DMEK graft preparation is determining the size of the graft. Evaluating risks and benefits of transplanting larger or smaller grafts compared with the descemetorhexis performed following a standard DMEK procedure thus becomes important. Advanced techniques like pre-loaded DMEK requires pre-selection of graft diameter without physical examination of the eye making it more challenging. Therefore, recognizing the benefits of graft size and the number of transplanted endothelial cells becomes essential. Smaller DMEK grafts have been preferred and accepted for grafting. Larger diameter grafts have advantages but can be challenging due to higher detachment rates. We thus aim to review the challenges of preparing and delivering DMEK tissues with small or large diameter based on selected descemetorhexis area, discuss the outcomes based on different graft sizes, highlight related complications and suggest which cases may benefit from adopting smaller or larger graft size.},
	keywords = {Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelial Cells, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies, Visual Acuity},
	issn = {1755-3768},
	doi = {10.1111/aos.15202},
	author = {Parekh, Mohit and Romano, Davide and Wongvisavavit, Rintra and Coco, Giulia and Giannaccare, Giuseppe and Ferrari, Stefano and Rocha-de-Lossada, Carlos and Levis, Hannah J and Semeraro, Francesco and Calvo-de-Mora, Marina Rodr{\'\i}guez and Scorcia, Vincenzo and Romano, Vito}
}
@article {1798321,
	title = {Performance outcomes from a DMEK peeling and preparation wet lab},
	journal = {BMJ Open Ophthalmol},
	volume = {9},
	number = {1},
	year = {2024},
	month = {2024 Jan 25},
	abstract = {OBJECTIVE: To evaluate the Descemet membrane endothelial keratoplasty (DMEK) preparation performance of trainee surgeons in an ex vivo human donor cornea DMEK wet lab simulation setting.

METHODS: Human donor corneoscleral rims unsuitable for transplantation were obtained from Moorfields Lions Eye Bank. At the wet lab, graft stripping was performed by scoring the peripheral endothelium. The trypan blue positive cells (TBPC) and cell density (cells/mm2-reticule count) were counted manually before and after stripping. The procedural time, peripheral and central tears and complete peel-off were also recorded and analysed.

RESULTS: Eight trainee surgeons attended the wet lab each attempting three DMEKs. Between the first and last attempts a significant decrease was seen in the procedural time (17.6 min vs 10.6 min (p\&lt;0.05)) and the TBPC \% (12.9\% vs 3.8\% (p\&lt;0.05)). The percentage of tears peripherally and centrally also reduced between the first and the last trials (50\% vs 13\% (p=0.2226) and 38\% vs 0\% (p=0.1327)). A significant correlation was found between longer peeling times and higher TBPC \% (p\&lt;0.001) with a 0.7\% endothelial mortality increase for each additional minute required to complete the peel.

CONCLUSIONS: DMEK wet labs provide a controlled risk-free learning opportunity for trainee surgeons to improve confidence and competence. Wet labs improve the success rate of DMEK graft preparation as well as flatten the learning curve. This emphasises the importance of continued support for the expansion of this valuable learning resource, promoting wider uptake of DMEK surgery.},
	keywords = {Cornea, Descemet Stripping Endothelial Keratoplasty, Eye Banks, Humans, Learning Curve, Tissue Donors, Trypan Blue},
	issn = {2397-3269},
	doi = {10.1136/bmjophth-2023-001540},
	author = {Parekh, Mohit and Wallace, Alexander George and Airaldi, Matteo and Ruzza, Alessandro and Ferrari, Stefano and Romano, Vito and Ahmad, Sajjad}
}
@article {1522712,
	title = {Advances in Telemedicine in Ophthalmology},
	journal = {Semin Ophthalmol},
	year = {2020},
	month = {2020 Jul 09},
	pages = {1-6},
	abstract = {Telemedicine is the provision of healthcare-related services from a distance and is poised to move healthcare from the physician{\textquoteright}s office back into the patient{\textquoteright}s home. The field of ophthalmology is often at the forefront of technological advances in medicine including telemedicine and the use of artificial intelligence. Multiple studies have demonstrated the reliability of tele-ophthalmology for use in screening and diagnostics and have demonstrated benefits to patients, physicians, as well as payors. There remain obstacles to widespread implementation, but recent legislation and regulation passed due to the devastating COVID-19 pandemic have helped to reduce some of these barriers. This review describes the current status of tele-ophthalmology in the United States including benefits, hurdles, current programs, technology, and developments in artificial intelligence. With ongoing advances patients may benefit from improved detection and earlier treatment of eye diseases, resulting in better care and improved visual outcomes.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1789675},
	author = {Parikh, Deep and Armstrong, Grayson and Liou, Victor and Husain, Deeba}
}
@article {1498263,
	title = {Surgical Confusions in Ophthalmology: Description, Analysis, and Prevention of Errors from 2006 through 2017},
	journal = {Ophthalmology},
	volume = {127},
	number = {3},
	year = {2020},
	month = {2020 Mar},
	pages = {296-302},
	abstract = {PURPOSE: To characterize surgical confusions in ophthalmology to determine their incidence, root causes, and impact on patients and physicians. DESIGN: Retrospective cohort study of errors in ophthalmic surgical procedures between January 1, 2006, and December 31,\&nbsp;2017. PARTICIPANTS: One hundred forty-three cases involving surgical confusions. METHODS: Cases were identified by the Ophthalmic Mutual Insurance Company from closed case files and by the New York State Health Department from the New York Patient Occurrence Reporting and Tracking program that identified the surgical confusions. MAIN OUTCOME MEASURES: Incidence and impact by intended surgery, error type, and root cause as well as preventability by the Universal Protocol. RESULTS: Of the 143 cases of surgical confusions identified, 92 cases (64.3\%) were deemed preventable by the Universal Protocol. Approximately two thirds, 95 cases (66.4\%), were cases of incorrect implants being used during cataract surgery (cataract extraction and intraocular lens implantation), of which 33 cases (34.7\%) were not preventable by the Universal Protocol. Wrong eye blocks or anesthesia accounted for 20 cases (14.0\%), incorrect eye procedures accounted for 10 cases (7.00\%), incorrect refractive surgery measurements accounted for 6 cases (4.20\%), incorrect patient or procedure accounted for 5 cases (3.50\%), incorrect intraocular gas concentration accounted for 4 cases (2.80\%), and incorrect medication in surgery accounted for 3 cases (2.10\%). The most common root cause of confusion was an inadequately performed time out, which was responsible for nearly one third of all surgical confusions, 46 cases (32.2\%). Incorrect lens orders or calculations before surgery (so-called upstream errors) were the second most common cause of surgical confusion, involving 31 cases (21.7\%). The average legal indemnity for incorrect implant during cataract surgery was $57 514 (United States dollars). The average indemnity for incorrect refractive surgery measurement was $123 125, that for incorrect eye procedure was $50 000, and that for incorrect gas concentration was $220 844. CONCLUSIONS: Most surgical confusions could have been prevented by following the Universal Protocol properly. However, upstream errors, originating in the clinic or office before surgery, and ineffective communication during time outs suggest a need for modification of the Universal Protocol.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.07.013},
	author = {Parikh, Ravi and Palmer, Valerie and Kumar, Aman and Simon, John W}
}
@article {1328898,
	title = {Multimodal Imaging to Monitor Recurrent Serpiginous Choroiditis},
	journal = {Ophthalmology},
	volume = {125},
	number = {8},
	year = {2018},
	month = {2018 Aug},
	pages = {1252},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.06.009},
	author = {Parikh, Ravi and Sakurada, Yoichi and Yannuzzi, Lawrence A}
}
@article {1417571,
	title = {Comparison of Ophthalmic Medication Prices Between the United States and Australia},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Jan 10},
	abstract = {Importance: Health care prices may drive differences in health care costs across high-income nations. Adalimumab, ranibizumab, and aflibercept are high-cost medications in the United States and Australia. A comparison of their prices over time may elucidate how ophthalmic medication prices contribute to health care costs. Objective: To compare changes in the prices of adalimumab, ranibizumab, and aflibercept in the United States and Australia, the highest and lowest spenders on health care, respectively, among high-income nations. Design, Setting, and Participants: This retrospective price comparison study examined prices paid by government entities in the United States (Medicare) and Australia (Pharmaceuticals and Benefits Scheme). The analysis and data collection were conducted from March 28 to May 4, 2018, in accordance with guidelines set by the International Society for Pharmacoeconomics and Outcomes Research Task Force on Good Research Practices and prior published studies. No human participants or related data were included in this study. Exposures: The change in mean prices of adalimumab, ranibizumab, and aflibercept in the United States and Australia. Main Outcomes and Measures: Initial, final, and change in medication price annually from 2013 to 2017 in inflation-adjusted 2017 US dollars. Results: The mean prices (US dollar prices unadjusted for inflation) in 2013 and 2017 in the United States were $1114 ($1053) and $1818 ($1818), respectively, for adalimumab; $2102 ($1988) and $1904 ($1904), respectively, for ranibizumab; and $2074 ($1961) and $1956 ($1956), respectively, for aflibercept. The mean (Australian dollar prices unadjusted for inflation) 2013 and 2017 prices in Australia were $1854 (A $1797) and $1206 (A $1574), respectively, for adalimumab; $2157 (A $2090) and $972 (A $1268), respectively, for ranibizumab; and $2030 ($1967) and $996 ($1300), respectively, for aflibercept. The estimated annual change in price for adalimumab was +12.8\% (95\% CI, 9.1\%-16.5\%) in the United States compared with -11.1\% (95\% CI, -15.0\% to -7.1\%) in Australia, a difference of 23.9\% per year (95\% CI, 19.7\%-28.0\%; P \&lt; .001). The annual change in price for ranibizumab was -2.6\% (95\% CI, -3.9\% to -1.3\%) in the United States compared with -18.5\% (95\% CI, -29.3\% to -7.8\%) in Australia, a difference of 15.9\% per year (95\% CI, 7.6\%-24.2\%; P = .003). The annual change in price for aflibercept was -1.5\% (95\% CI, -2.2\% to -0.7\%) in the United States compared with -16.9\% (95\% CI, -25.1\% to -8.6\%) in Australia, a difference of 15.4\% (95\% CI, 9.1\%-21.8\%; P = .001). Conclusions and Relevance: Results of this study indicate that the prices of adalimumab, ranibizumab, and aflibercept significantly decreased during the past 5 years in Australia compared with the United States. These data do not indicate why these differences are noted or what actions might affect future pricing in either country.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.6395},
	author = {Parikh, Ravi and Feng, Paula W and Tainsh, Laurel and Sakurada, Yoichi and Balaratnasingam, Chandrakumar and Khurana, Rahul N and Hemmati, Houman and Modi, Yasha S}
}
@article {1538324,
	title = {Re: Gedde et al.: Ophthalmology resident surgical competence: a survey of program directors (Ophthalmology. 2020;127(8):1123-1125)},
	journal = {Ophthalmology},
	volume = {127},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {e91-e92},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.05.018},
	author = {Parikh, Ravi and Armstrong, Grayson W and Nguyen, Alexander T}
}
@article {1761956,
	title = {A Novel Ophthalmic Telemedicine Program for Follow-Up of Minor Ophthalmic Emergencies},
	journal = {Telemed J E Health},
	volume = {30},
	number = {3},
	year = {2024},
	month = {2024 Mar},
	pages = {835-840},
	abstract = {Background: Near-term follow-up for minor ophthalmic emergencies is important to ensure positive patient outcomes but can impose logistical challenges for patients and ophthalmology practices. While ophthalmic telemedicine has been used for screening and triage, its feasibility and safety for follow-up care for minor ophthalmic emergencies have not been reported. The objective of this study was to report initial results of a novel virtual emergency department (ED) follow-up clinic. Methods: Retrospective cross-sectional study of patients discharged from the ophthalmic ED who required near-term follow-up and carried diagnoses suitable for virtual evaluation, between December 6, 2021, and June 26, 2022, at a single tertiary eye care center. Main outcome measures included missed appointment rate, time interval between ED encounter and virtual follow-up, clinical diagnoses, and referrals after telemedicine follow-up (including for urgent ambulatory and ED evaluation). Results: A total of 145 virtual visits were scheduled with 99 (68.3\%) completed appointments, yielding a no-show rate of 31.7\%. Of the completed visits, the mean time interval between ED evaluation and virtual follow-up was 8.3 days (standard deviation {\textpm}3.9). Eighty-four (84.9\%) visits were video-based and 15 (15.1\%) were audio-only. Seventy-nine (94\%) had at least one aspect of the ophthalmic examination documented. The most common diagnoses were chalazion (18), conjunctivitis (13), corneal abrasion (12), and encounter after corneal foreign body removal (7). After virtual follow-up, 23 patients (23.2\%) had subsequent referrals, and no patients re-presented to the ophthalmic ED. Conclusions: Ophthalmic telemedicine may be a safe and feasible modality for providing timely post-acute near-term follow-up care for patients with appropriate ophthalmic diagnoses.},
	keywords = {Cross-Sectional Studies, Emergencies, Emergency Service, Hospital, Follow-Up Studies, Humans, Retrospective Studies, Telemedicine},
	issn = {1556-3669},
	doi = {10.1089/tmj.2023.0129},
	author = {Parikh, Ayush A and Liebman, Daniel L and Armstrong, Grayson W}
}
@article {1452972,
	title = {Incidence of New Choroidal Neovascularization in Fellow Eyes of Patients With Age-Related Macular Degeneration Treated With Intravitreal Aflibercept or Ranibizumab},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Jul 11},
	abstract = {Importance: Incidence of conversion to neovascular age-related macular degeneration (nAMD) in untreated fellow eyes of patients who are treated for nAMD in 1 eye with anti-vascular endothelial growth factor agents provides important prognostic information to clinically manage patients. Objective: To investigate the association of treatment assignment (intravitreal aflibercept vs ranibizumab) and baseline characteristics with fellow eye conversion to nAMD in the VEGF (Vascular Endothelial Growth Factor) Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies. Design, Setting, and Participants: This post hoc analysis of the VIEW 1 and VIEW 2 studies (randomized, double-masked, active-controlled, multicenter, 96-week, phase 3 trials comparing the efficacy and safety of intravitreal aflibercept in 2457 patients with treatment-naive eyes with nAMD) analyzed a subgroup of participants treated for nAMD in 1 eye who had untreated fellow eyes without neovascularization at baseline. All participants in the VIEW studies were included in 1 of 4 groups: ranibizumab, 0.5 mg, every 4 weeks; aflibercept, 2 mg, every 4 weeks; aflibercept, 0.5 mg, every 4 weeks; or aflibercept, 2 mg, every 8 weeks after 3 injections at 4-week intervals. Data collection in the VIEW studies occurred from July 2007 to August 2011; the data analysis presented in this report took place from April 2016 to November 2018. Interventions: Patients received no treatment in the fellow eyes unless after conversion to nAMD, when any treatment approved by heath authorities was given per the investigators{\textquoteright} discretion. Main Outcomes and Measures: Incidence of conversion to nAMD in patients with untreated fellow eyes that had not had clinical signs of neovascularization at baseline. Results: A total of 1561 participants were included in this analysis. At 96 weeks, 375 patients (24.0\%) experienced cases of conversion to neovascular disease in the fellow eye, including 107 of the 399 individuals who received ranibizumab, 0.5 mg, every 4 weeks; 93 of the 387 individuals who received aflibercept, 2 mg, every 4 weeks; 84 of the 387 individuals who received aflibercept, 0.5 mg, every 4 weeks; and 91 of the 388 individuals who received aflibercept, 2 mg, every 8 weeks after 3 doses at 4-week intervals. The rates were 18.1, 16.2, 14.7, and 16.0 per 100 patient-years at risk at week 96, respectively. On multivariate analysis, fellow eye conversion was associated with increasing patient age (per 10 years) at baseline (hazard ratio [HR], 1.20 [95\% CI, 1.05-1.36]), female sex (HR, 1.32 [95\% CI, 1.06-1.63]), intraretinal fluid in the study eye at baseline (HR, 1.28 [95\% CI, 1.02-1.61]), and increasing choroidal neovascularization lesion size (per 10 mm2) in the study eye at baseline (HR, 1.29 [95\% CI, 1.06-1.57]). Rates of fellow eye conversion were similar with either of the treatments. Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, patients with active nAMD in 1 eye appeared to have a high risk for fellow eye conversion. Such patients should be monitored closely.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.1947},
	author = {Parikh, Ravi and Avery, Robert L and Saroj, Namrata and Thompson, Desmond and Freund, K Bailey}
}
@article {1528420,
	title = {Fibroblast Growth Factor Receptor Inhibitor-Associated Retinopathy},
	journal = {JAMA Ophthalmol},
	volume = {138},
	number = {10},
	year = {2020},
	month = {2020 Oct 01},
	pages = {1101-1103},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.2778},
	author = {Parikh, Deep and Eliott, Dean and Kim, Leo A}
}
@article {1439858,
	title = {Spontaneous Superior Ophthalmic Vein Thrombosis in a Transgender Man with Systemic Lupus Erythematosus},
	journal = {LGBT Health},
	volume = {6},
	number = {4},
	year = {2019},
	month = {2019 May/Jun},
	pages = {202-204},
	issn = {2325-8306},
	doi = {10.1089/lgbt.2018.0099},
	author = {Park, Jeayoung and Armstrong, Grayson W and Cestari, Dean M}
}
@article {1364523,
	title = {Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)},
	journal = {Biosci Rep},
	volume = {32},
	number = {4},
	year = {2012},
	month = {2012 Aug},
	pages = {393-400},
	abstract = {The plasma level of LPA (lysophosphatidic acid) (200-600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA.},
	keywords = {Angiogenesis Inducing Agents, Angiogenesis Inhibitors, Animals, Cell Line, Cell Movement, Culture Media, Conditioned, Fibroblast Growth Factor 2, Human Umbilical Vein Endothelial Cells, Humans, Lysophospholipids, Microvessels, Paxillin, Phosphorylation, Primary Cell Culture, Rats, Skin, Vascular Endothelial Growth Factor A},
	issn = {1573-4935},
	doi = {10.1042/BSR20120033},
	author = {Park, Eun Young and Kazlauskas, Andrius}
}
@article {1309966,
	title = {A case of Graves{\textquoteright} ophthalmopathy associated with pembrolizumab (Keytruda) therapy},
	journal = {J AAPOS},
	year = {2018},
	month = {2018 Apr 04},
	abstract = {We present the first reported case of Graves{\textquoteright} orbitopathy induced by pembrolizumab, a new FDA-approved drug used for the treatment of multiple refractory solid tumors and classic Hodgkin lymphoma. Pembrolizumab elicits T-lymphocyte proliferation; we suspect that thyroid eye disease may result in some cases.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2018.01.006},
	author = {Park, Ella S Y and Rabinowits, Guilherme and Hamnvik, Ole-Petter R and Dagi, Linda R}
}
@article {742291,
	title = {Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects.},
	journal = {Am J Hum Genet},
	volume = {98},
	number = {6},
	year = {2016},
	month = {2016 Jun 2},
	pages = {1220-7},
	abstract = {Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development.},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2016.03.023},
	author = {Park, Jong G and Tischfield, Max A and Nugent, Alicia A and Cheng, Long and Di Gioia, Silvio Alessandro and Chan, Wai-Man and Maconachie, Gail and Bosley, Thomas M and Summers, C Gail and Hunter, David G and Robson, Caroline D and Gottlob, Irene and Engle, Elizabeth C}
}
@article {1363176,
	title = {Induction of WNT inhibitory factor 1 expression by M{\"u}llerian inhibiting substance/antiMullerian hormone in the M{\"u}llerian duct mesenchyme is linked to M{\"u}llerian duct regression},
	journal = {Dev Biol},
	volume = {386},
	number = {1},
	year = {2014},
	month = {2014 Feb 01},
	pages = {227-36},
	abstract = {A key event during mammalian sexual development is regression of the M{\"u}llerian ducts (MDs) in the bipotential urogenital ridges (UGRs) of fetal males, which is caused by the expression of M{\"u}llerian inhibiting substance (MIS) in the Sertoli cells of the differentiating testes. The paracrine signaling mechanisms involved in MD regression are not completely understood, particularly since the receptor for MIS, MISR2, is expressed in the mesenchyme surrounding the MD, but regression occurs in both the epithelium and mesenchyme. Microarray analysis comparing MIS signaling competent and Misr2 knockout embryonic UGRs was performed to identify secreted factors that might be important for MIS-mediated regression of the MD. A seven-fold increase in the expression of Wif1, an inhibitor of WNT/β-catenin signaling, was observed in the Misr2-expressing UGRs. Whole mount in situ hybridization of Wif1 revealed a spatial and temporal pattern of expression consistent with Misr2 during the window of MD regression in the mesenchyme surrounding the MD epithelium that was absent in both female UGRs and UGRs knocked out for Misr2. Knockdown of Wif1 expression in male UGRs by Wif1-specific siRNAs beginning on embryonic day 13.5 resulted in MD retention in an organ culture assay, and exposure of female UGRs to added recombinant human MIS induced Wif1 expression in the MD mesenchyme. Knockdown of Wif1 led to increased expression of β-catenin and its downstream targets TCF1/LEF1 in the MD mesenchyme and to decreased apoptosis, resulting in partial to complete retention of the MD. These results strongly suggest that WIF1 secretion by the MD mesenchyme plays a role in MD regression in fetal males.},
	keywords = {Animals, Anti-Mullerian Hormone, Antigens, CD, Antigens, Differentiation, B-Lymphocyte, Extracellular Matrix Proteins, Female, Gene Expression Profiling, Gene Expression Regulation, Developmental, Intercellular Signaling Peptides and Proteins, Male, Mesoderm, Mice, Mice, Inbred C57BL, Mullerian Ducts, Oligonucleotide Array Sequence Analysis, Receptors, Peptide, Receptors, Transforming Growth Factor beta, Recombinant Proteins, RNA, Small Interfering, Sertoli Cells, Signal Transduction, Time Factors},
	issn = {1095-564X},
	doi = {10.1016/j.ydbio.2013.12.015},
	author = {Park, Joo Hyun and Tanaka, Yoshihiro and Arango, Nelson A and Zhang, Lihua and Benedict, L Andrew and Roh, Miin and Donahoe, Patricia K and Teixeira, Jose M}
}
@article {1532379,
	title = {Artifact Rates for 2D Retinal Nerve Fiber Layer Thickness Versus 3D Neuroretinal Rim Thickness Using Spectral-Domain Optical Coherence Tomography},
	journal = {Transl Vis Sci Technol},
	volume = {9},
	number = {10},
	year = {2020},
	month = {2020 Sep},
	pages = {10},
	abstract = {Purpose: To compare the rates of clinically significant artifacts for two-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness versus three-dimensional (3D) neuroretinal rim thickness using spectral-domain optical coherence tomography (SD-OCT). Methods: Only one eye per patient was used for analysis of 120 glaucoma patients and 114 normal patients. For RNFL scans and optic nerve scans, 15 artifact types were calculated per B-scan and per eye. Neuroretinal rim tissue was quantified by the minimum distance band (MDB). Global MDB neuroretinal rim thicknesses were calculated before and after manual deletion of B-scans with artifacts and subsequent automated interpolation. A clinically significant artifact was defined as one requiring manual correction or repeat scanning. Results: Among glaucomatous eyes, artifact rates per B-scan were significantly more common in RNFL scans (61.7\%, 74 of 120) compared to B-scans in neuroretinal rim volume scans (20.9\%, 1423 of 6820) (95\% confidence interval [CI], 31.6-50.0; \&lt; 0.0001). For clinically significant artifact rates per eye, optic nerve scans had significantly fewer artifacts (15.8\% of glaucomatous eyes, 13.2\% of normal eyes) compared to RNFL scans (61.7\% of glaucomatous eyes, 25.4\% of normal eyes) (glaucoma group: 95\% CI, 34.1-57.5, \&lt; 0.0001; normal group: 95\% CI, 1.3-23.3, = 0.03). Conclusions: Compared to the most commonly used RNFL thickness scans, optic nerve volume scans less frequently require manual correction or repeat scanning to obtain accurate measurements. Translational Relevance: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.},
	issn = {2164-2591},
	doi = {10.1167/tvst.9.10.10},
	author = {Park, Elli A and Tsikata, Edem and Lee, Jenny Jyoung and Shieh, Eric and Braaf, Boy and Vakoc, Benjamin J and Bouma, Brett E and de Boer, Johannes F and Chen, Teresa C}
}
@article {1282141,
	title = {Endomucin inhibits VEGF-induced endothelial cell migration, growth, and morphogenesis by modulating VEGFR2 signaling},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Dec 07},
	pages = {17138},
	abstract = {Angiogenesis is central to both normal and pathologic processes. Endothelial cells (ECs) express O-glycoproteins that are believed to play important roles in vascular development and stability. Endomucin-1 (EMCN) is a type I O-glycosylated, sialic-rich glycoprotein, specifically expressed by venous and capillary endothelium. Evidence has pointed to a potential role for EMCN in angiogenesis but it had not been directly investigated. In this study, we examined the role of EMCN in angiogenesis by modulating EMCN levels both in vivo and in vitro. Reduction of EMCN in vivo led to the impairment of angiogenesis during normal retinal development in vivo. To determine the cellular basis of this inhibition, gain- and loss-of-function studies were performed in human retinal EC (HREC) in vitro by EMCN over-expression using adenovirus or EMCN gene knockdown by siRNA. We show that EMCN knockdown reduced migration, inhibited cell growth without compromising cell survival, and suppressed tube morphogenesis of ECs, whereas over-expression of EMCN led to increased migration, proliferation and tube formation. Furthermore, knockdown of EMCN suppressed VEGF-induced signaling as measured by decreased phospho-VEGFR2, phospho-ERK1/2 and phospho-p38-MAPK levels. These results suggest a novel role for EMCN as a potent regulator of angiogenesis and point to its potential as a new therapeutic target for angiogenesis-related diseases.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-16852-x},
	author = {Park-Windhol, Cindy and Ng, Yin Shan and Yang, Jinling and Primo, Vincent and Saint-Geniez, Magali and D{\textquoteright}Amore, Patricia A}
}
@article {1773576,
	title = {Author Correction: Endomucin knockdown inhibits VEGF-induced endothelial cell migration, growth, and morphogenesis by modulating VEGFR2 signaling},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Oct 03},
	pages = {16620},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-43612-x},
	author = {Park-Windhol, Cindy and Ng, Yin Shan and Yang, Jinling and Primo, Vincent and Saint-Geniez, Magali and D{\textquoteright}Amore, Patricia A}
}
@article {655066,
	title = {Disorders of Vascular Permeability.},
	journal = {Annu Rev Pathol},
	volume = {11},
	year = {2016},
	month = {2016 May 23},
	pages = {251-81},
	abstract = {The endothelial barrier maintains vascular and tissue homeostasis and modulates many physiological processes, such as angiogenesis. Vascular barrier integrity can be disrupted by a variety of soluble permeability factors, and changes in barrier function can exacerbate tissue damage during disease progression. Understanding endothelial barrier function is critical for vascular homeostasis. Many of the signaling pathways promoting vascular permeability can also be triggered during disease, resulting in prolonged or uncontrolled vascular leak. It is believed that recovery of the normal vasculature requires diminishing this hyperpermeable state. Although the molecular mechanisms governing vascular leak have been studied over the last few decades, recent advances have identified new therapeutic targets that have begun to show preclinical and clinical promise. These approaches have been successfully applied to an increasing number of disease conditions. New perspectives regarding how vascular leak impacts the progression of various diseases are highlighted in this review.},
	issn = {1553-4014},
	doi = {10.1146/annurev-pathol-012615-044506},
	author = {Park-Windhol, Cindy and D{\textquoteright}Amore, Patricia A}
}
@article {1698256,
	title = {Reliability of Ahmed glaucoma valve surgical videos for educational purposes},
	journal = {Int Ophthalmol},
	volume = {43},
	number = {9},
	year = {2023},
	month = {2023 Sep},
	pages = {3425-3432},
	abstract = {PURPOSE: The use of video-based social media platforms is increasing among trainee residents, fellows, and practicing ophthalmologists. In this study, we objectively evaluate the quality of Ahmed glaucoma valve (AGV) implantation videos on open access, video-based internet platforms. DESIGN: Internet-based cross-sectional study. PARTICIPANTS: Not applicable. METHODS: In this cross-sectional study, 23 websites publishing medical surgery training video content were queried using the keyword "Ahmed glaucoma valve implantation". MAIN OUTCOME MEASURES: The descriptive statistics of video parameters were noted, and the videos were assessed using established scoring systems-Sandvik, Health on the Net Foundation Code of Conduct (HON code), mDISCERN, and Global Quality Score (GQS) scores. Video Quality Score (VQS) was determined based on the 14 steps per the AGV implantation rubric. RESULTS: One hundred and nineteen videos were evaluated, and 35 were excluded. The total quality of all 84 videos according to their Sandvik, HON Code, GQS, DISCERN, and VQS scores was 11.79 {\textpm} 1.70 (excellent quality), 6.86 {\textpm} 0.75 (excellent quality), 3.97 {\textpm} 0.93 (good quality), 3.26 {\textpm} 0.66 (fair quality) and 11.45 {\textpm} 2.67 (good quality), respectively. No significant correlation was found between the descriptive parameters and video quality score. However, no significant correlation was found between the descriptive parameters and video quality score. CONCLUSIONS: The objective analysis showed that the video quality ranged from good to excellent. AGV implantation videos were sparse on exclusive ophthalmology surgical video portals. Therefore, more peer-reviewed videos following standardized rubric are needed on open-access surgical video platforms.},
	keywords = {Cross-Sectional Studies, Educational Status, Glaucoma, Humans, Internet, Reproducibility of Results},
	issn = {1573-2630},
	doi = {10.1007/s10792-023-02734-x},
	author = {Parmar, Uday Pratap Singh and Ichhpujani, Parul and Chahal, Rutvi and Singh, Rohan Bir}
}
@article {1580466,
	title = {Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye},
	journal = {JAMA},
	volume = {325},
	number = {8},
	year = {2021},
	month = {2021 02 23},
	pages = {753-764},
	abstract = {Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P \&lt; 2.5 {\texttimes} 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0\%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0\%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3\% vs 0.30\%, respectively; odds ratio, 3.55 [95\% CI, 2.07-6.10]; P = 6.1 {\texttimes} 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2\% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1\% without exfoliation syndrome (odds ratio, 1.82 [95\% CI, 1.47-2.26]; P \&lt; .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4\% [interquartile range, 78.7\%-98.2\%] for the 34 deficient variants). CYP39A1 transcript expression was 47\% lower (95\% CI, 30\%-64\% lower; P \&lt; .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.},
	issn = {1538-3598},
	doi = {10.1001/jama.2021.0507},
	author = {Genetics of Exfoliation Syndrome Partnership and Li, Zheng and Wang, Zhenxun and Lee, Mei Chin and Zenkel, Matthias and Peh, Esther and Ozaki, Mineo and Topouzis, Fotis and Nakano, Satoko and Chan, Anita and Chen, Shuwen and Williams, Susan E I and Orr, Andrew and Nakano, Masakazu and Kobakhidze, Nino and Zarnowski, Tomasz and Popa-Cherecheanu, Alina and Mizoguchi, Takanori and Manabe, Shin-Ichi and Hayashi, Ken and Kazama, Shigeyasu and Inoue, Kenji and Mori, Yosai and Miyata, Kazunori and Sugiyama, Kazuhisa and Higashide, Tomomi and Chihara, Etsuo and Ideta, Ryuichi and Ishiko, Satoshi and Yoshida, Akitoshi and Tokumo, Kana and Kiuchi, Yoshiaki and Ohashi, Tsutomu and Sakurai, Toshiya and Sugimoto, Takako and Chuman, Hideki and Aihara, Makoto and Inatani, Masaru and Mori, Kazuhiko and Ikeda, Yoko and Ueno, Morio and Gaston, Daniel and Rafuse, Paul and Shuba, Lesya and Saunders, Joseph and Nicolela, Marcelo and Chichua, George and Tabagari, Sergo and Founti, Panayiota and Sim, Kar Seng and Meah, Wee Yang and Soo, Hui Meng and Chen, Xiao Yin and Chatzikyriakidou, Anthi and Keskini, Christina and Pappas, Theofanis and Anastasopoulos, Eleftherios and Lambropoulos, Alexandros and Panagiotou, Evangelia S and Mikropoulos, Dimitrios G and Kosior-Jarecka, Ewa and Cheong, Augustine and Li, Yuanhan and Lukasik, Urszula and Nongpiur, Monisha E and Husain, Rahat and Perera, Shamira A and {\'A}lvarez, Lydia and Garc{\'\i}a, Montserrat and Gonz{\'a}lez-Iglesias, H{\'e}ctor and Cueto, Andr{\'e}s F V and Cueto, Luis F V and Martin{\'o}n-Torres, Federico and Salas, Antonio and Oguz, {\c C}ilingir and Tamcelik, Nevbahar and Atalay, Eray and Batu, Bilge and Irkec, Murat and Aktas, Dilek and Kasim, Burcu and Astakhov, Yury S and Astakhov, Sergei Y and Akopov, Eugeny L and Giessl, Andreas and Mardin, Christian and Hellerbrand, Claus and Cooke Bailey, Jessica N and Igo, Robert P and Haines, Jonathan L and Edward, Deepak P and Heegaard, Steffen and Davila, Sonia and Tan, Patrick and Kang, Jae H and Pasquale, Louis R and Kruse, Friedrich E and Reis, Andr{\'e} and Carmichael, Trevor R and Hauser, Michael and Ramsay, Michele and Mossb{\"o}ck, Georg and Yildirim, Nilgun and Tashiro, Kei and Konstas, Anastasios G P and Coca-Prados, Miguel and Foo, Jia Nee and Kinoshita, Shigeru and Sotozono, Chie and Kubota, Toshiaki and Dubina, Michael and Ritch, Robert and Wiggs, Janey L and Pasutto, Francesca and Schl{\"o}tzer-Schrehardt, Ursula and Ho, Ying Swan and Aung, Tin and Tam, Wai Leong and Khor, Chiea Chuen}
}
@article {1360118,
	title = {Permanent neuroglial remodeling of the retina following infiltration of CSF1R inhibition-resistant peripheral monocytes},
	journal = {Proc Natl Acad Sci U S A},
	volume = {115},
	number = {48},
	year = {2018},
	month = {2018 Nov 27},
	pages = {E11359-E11368},
	abstract = {Previous studies have demonstrated that ocular injury can lead to prompt infiltration of bone-marrow-derived peripheral monocytes into the retina. However, the ability of these cells to integrate into the tissue and become microglia has not been investigated. Here we show that such peripheral monocytes that infiltrate into the retina after ocular injury engraft permanently, migrate to the three distinct microglia strata, and adopt a microglia-like morphology. In the absence of ocular injury, peripheral monocytes that repopulate the retina after depletion with colony-stimulating factor 1 receptor (CSF1R) inhibitor remain sensitive to CSF1R inhibition and can be redepleted. Strikingly, consequent to ocular injury, the engrafted peripheral monocytes are resistant to depletion by CSF1R inhibitor and likely express low CSF1R. Moreover, these engrafted monocytes remain proinflammatory, expressing high levels of MHC-II, IL-1β, and TNF-α over the long term. The observed permanent neuroglia remodeling after injury constitutes a major immunological change that may contribute to progressive retinal degeneration. These findings may also be relevant to other degenerative conditions of the retina and the central nervous system.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1807123115},
	author = {Paschalis, Eleftherios I and Lei, Fengyang and Zhou, Chengxin and Kapoulea, Vassiliki and Dana, Reza and Chodosh, James and Vavvas, Demetrios G and Dohlman, Claes H}
}
@article {280826,
	title = {Removal of Silicone Oil From Intraocular Lens Using Novel Surgical Materials.},
	journal = {Transl Vis Sci Technol},
	volume = {3},
	number = {5},
	year = {2014},
	month = {2014 Sep},
	pages = {4},
	abstract = {PURPOSE: To design, fabricate, and evaluate novel materials to remove silicone oil (SiO) droplets from intraocular lenses (IOL) during vitreoretinal surgery. METHODS: Three different designs were fabricated using soft lithography of polydimethylsiloxane (PDMS), three-dimensional (3D) inverse PDMS fabrication using water dissolvable particles, and atomic layer deposition (ALD) of alumina (Al2O3) on surgical cellulose fibers. Laboratory tests included static and dynamic contact angle (CA) measurements with water and SiO, nondestructive x-ray microcomputer tomography (micro-CT), and microscopy. SiO removal was performed in vitro and ex vivo using implantable IOLs and explanted porcine eyes. RESULTS: All designs exhibited enhanced hydrophobicity and oleophilicity. Static CA measurements with water ranged from 131{\textdegree} to 160{\textdegree} and with SiO CA approximately 0{\textdegree} in 120 seconds following exposure. Nondestructive x-ray analysis of the 3D PDMS showed presence of interconnected polydispersed porosity of 100 to 300 μm in diameter. SiO removal from IOLs was achieved in vitro and ex vivo using standard 20-G vitrectomy instrumentation. CONCLUSION: Removal of SiO from IOLs can be achieved using materials with lower surface energy than that of the IOLs. This can be achieved using appropriate surface chemistry and surface topography. Three designs, with enhanced hydrophobic properties, were fabricated and tested in vitro and ex vivo. All materials remove SiO within an aqueous environment. Preliminary ex vivo results were very promising, opening new possibilities for SiO removal in vitreoretinal surgeries. TRANSLATIONAL RELEVANCE: This is the first report of an instrument that can lead to successful removal of SiO from the surface of IOL. In addition to the use of this instrument/material in medicine it can also be used in the industry, for example, retrieval of oil spills from bodies of water.},
	issn = {2164-2591},
	doi = {10.1167/tvst.3.5.4},
	author = {Paschalis, Eleftherios I and Eliott, Dean and Vavvas, Demetrios G}
}
@article {1773551,
	title = {The prophylactic value of TNF-α inhibitors against retinal cell apoptosis and optic nerve axon loss after corneal surgery or trauma},
	journal = {Acta Ophthalmol},
	year = {2023},
	month = {2023 Oct 06},
	abstract = {BACKGROUND AND PURPOSE: Late secondary glaucoma is an often-severe complication after acute events like anterior segment surgery, trauma and infection. TNF-α is a major mediator that is rapidly upregulated, diffusing also to the retina and causes apoptosis of the ganglion cells and degeneration of their optic nerve axons (mediating steps to glaucomatous damage). Anti-TNF-α antibodies are in animals very effective in protecting the retinal cells and the optic nerve-and might therefore be useful prophylactically against secondary glaucoma in future such patients. Here we evaluate (1) toxicity and (2) efficacy of two TNF-α inhibitors (adalimumab and infliximab), in rabbits by subconjunctival administration. METHODS: For drug toxicity, animals with normal, unburned corneas were injected with adalimumab (0.4, 4, or 40 mg), or infliximab (1, 10, or 100 mg). For drug efficacy, other animals were subjected to alkali burn before such injection, or steroids (for control). The rabbits were evaluated clinically with slit lamp and photography, electroretinography, optical coherence tomography, and intraocular pressure manometry. A sub-set of eyes were stained ex vivo after 3 days for retinal cell apoptosis (TUNEL). In other experiments the optic nerves were evaluated by paraphenylenediamine staining after 50 or 90 days. Loss of retinal cells and optic nerve degeneration were quantified. RESULTS: Subconjunctival administration of 0.4 mg or 4.0 mg adalimumab were well tolerated, whereas 40.0 mg was toxic to the retina. 1, 10, or 100 mg infliximab were also well tolerated. Analysis of the optic nerve axons after 50 days confirmed the safety of 4.0 mg adalimumab and of 100 mg infliximab. For efficacy, 4.0 mg adalimumab subconjunctivally in 0.08 mL provided practically full protection against retinal cell apoptosis 3 days following alkali burn, and infliximab 100 mg only slightly less. At 90 days following burn injury, control optic nerves showed about 50\% axon loss as compared to 8\% in the adalimumab treatment group. CONCLUSIONS: Subconjunctival injection of 4.0 mg adalimumab in rabbits shows no eye toxicity and provides excellent neuroprotection, both short (3 days) and long-term (90 days). Our total. accumulated data from several of our studies, combined with the present paper, suggest that corneal injuries, including surgery, might benefit from routine administration of anti-TNF-α biologics to reduce inflammation and future secondary glaucoma.},
	issn = {1755-3768},
	doi = {10.1111/aos.15786},
	author = {Paschalis, Eleftherios I and Zhou, Chengxin and Sharma, Jyoti and Dohlman, Thomas H and Kim, Sarah and Lei, Fengyang and Chodosh, James and Vavvas, Demetrios and Urtti, Arto and Papaliodis, George and Dohlman, Claes H}
}
@article {1417572,
	title = {Blood Levels of Tumor Necrosis Factor Alpha and Its Type 2 Receptor Are Elevated in Patients with Boston Type I Keratoprosthesis},
	journal = {Curr Eye Res},
	volume = {44},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {599-606},
	abstract = {: Boston keratoprosthesis (KPro) patients are prone to glaucoma even with well-controlled intraocular pressure (IOP). Recent experimental data have shown that soluble tumor necrosis factor alpha (TNF-) after ocular injury may contribute to progressive retinal damage and subsequent glaucoma. This study evaluates the blood plasma levels of soluble TNF-, TNF receptors 1 (TNFR1) and 2 (TNFR2), and leptin in patients with Boston type I KPro. : Venous blood samples were collected from KPro patients with glaucoma (KPro G, =\&nbsp;19), KPro patients without glaucoma (KPro NoG, =\&nbsp;12), primary angle closure glaucoma without KPro (PACG, =\&nbsp;13), and narrow angles without glaucoma or KPro (NA, =\&nbsp;21). TNF-, TNFR1, TNFR2, and leptin levels were quantified using the enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate (ESR) was assessed using the Westergren test. Patients with underlying autoimmune conditions or diabetes were excluded from the study. : All groups had similar age, body mass index (BMI), IOP, and ESR ( >=\&nbsp;0.11). The mean time from KPro surgery to blood draw was 5.3\&nbsp;{\textpm}\&nbsp;3.7\&nbsp;years. Compared to NA patients (0.72\&nbsp;{\textpm}\&nbsp;0.3\&nbsp;pg/ml), KPro G and KPro NoG patients had higher blood plasma levels of TNF- (1.18\&nbsp;{\textpm}\&nbsp;0.58\&nbsp;pg/ml, =\&nbsp;0.006; 1.16\&nbsp;{\textpm}\&nbsp;0.50\&nbsp;pg/ml, =\&nbsp;0.04, respectively). Similarly, KPro G patients had higher blood plasma levels of TNFR2 (2768\&nbsp;{\textpm}\&nbsp;1368\&nbsp;pg/ml) than NA patients (2020\&nbsp;{\textpm}\&nbsp;435\&nbsp;pg/ml, =\&nbsp;0.048). In multivariate analysis, KPro status remained positively associated with TNF- levels (\&nbsp;=\&nbsp;0.36; 95\% confidence intervals [CI]: 0.14-0.58; =\&nbsp;0.002) and TNFR2 levels (\&nbsp;=\&nbsp;458.3; 95\% CI: 32.8-883.7; =\&nbsp;0.035) after adjusting for age, gender, BMI, glaucoma status, and ESR. TNFR1 and leptin levels were not significantly different in the study groups. : We detected elevated serum levels of TNF- and TNFR2 in KPro patients. Longitudinal studies are needed to establish TNF- and TNFR2 as serum biomarkers related to KPro surgery. : BCVA: best corrected visual acuity; BMI: body mass index; CDR: cup-to-disc ratio; EDTA: ethylenediaminetetraacetic acid; ELISA: enzyme-linked immunosorbent assay; ESR: erythrocyte sedimentation rate; HVF: Humphrey visual field; IOP: intraocular pressure; KPro G: keratoprosthesis with glaucoma; KPro NoG: keratoprosthesis without glaucoma; KPro: keratoprosthesis; MD: mean deviation; NA: narrow angle; non-KPro: without keratoprosthesis; PACG: primary angle closure glaucoma; RNFL: retinal nerve fiber layer; TNF-α: tumor necrosis factor alpha; TNFR1: tumor necrosis factor receptor 1; TNFR2: tumor necrosis factor receptor 2.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2019.1568500},
	author = {Paschalis, Eleftherios I and Taniguchi, Elise V and Chodosh, James and Pasquale, Louis R and Colby, Kathryn and Dohlman, Claes H and Shen, Lucy Q}
}
@article {1059796,
	title = {Mechanisms of Retinal Damage after Ocular Alkali Burns},
	journal = {Am J Pathol},
	volume = {187},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {1327-1342},
	abstract = {Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in\&nbsp;vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors. Tissue inflammation was assessed by immunohistochemistry and flow cytometry. The experiments confirmed that the retinal damage is not mediated by direct effect of the alkali, which is effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation reduction changes were restricted to the cornea and the anterior chamber, where they caused profound uveal inflammation and release of proinflammatory cytokines. The latter rapidly diffuse to the posterior segment, triggering retinal damage. Tumor necrosis factor-α was identified as a key proinflammatory mediator of retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion cell loss. Intraocular pressure elevation was not observed in experimental alkali burns. These findings illuminate the mechanism by which alkali burns cause retinal damage and may have importance in designing therapies for retinal protection.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2017.02.005},
	author = {Paschalis, Eleftherios I and Zhou, Chengxin and Lei, Fengyang and Scott, Nathan and Kapoulea, Vassiliki and Robert, Marie-Claude and Vavvas, Demetrios and Dana, Reza and Chodosh, James and Dohlman, Claes H}
}
@article {1402586,
	title = {Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries},
	journal = {J Immunol},
	volume = {202},
	number = {2},
	year = {2019},
	month = {2019 Jan 15},
	pages = {539-549},
	abstract = {Reactive microglia and infiltrating peripheral monocytes have been implicated in many neurodegenerative diseases of the retina and CNS. However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a proinflammatory phenotype that promotes neurodegeneration. In this study, we show that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as , , and in the retina, and abnormal engraftment of peripheral CCR2 CX3CR1 monocytes into the retina, which is associated with increased retinal ganglion cell loss, retinal nerve fiber layer thinning, and pigmentation onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension also cause similar changes. However, optic nerve crush injury-mediated retinal ganglion cell loss evokes neither peripheral monocyte response in the retina nor pigmentation, although peripheral CX3CR1 and CCR2 monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral monocyte infiltration and retinal pigment epithelium migration, and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1800982},
	author = {Paschalis, Eleftherios I and Lei, Fengyang and Zhou, Chengxin and Chen, Xiaohong Nancy and Kapoulea, Vassiliki and Hui, Pui-Chuen and Dana, Reza and Chodosh, James and Vavvas, Demetrios G and Dohlman, Claes H}
}
@article {1309963,
	title = {The Role of Microglia and Peripheral Monocytes in Retinal Damage after Corneal Chemical Injury},
	journal = {Am J Pathol},
	volume = {188},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {1580-1596},
	abstract = {Eyes that have experienced alkali burn to the surface are excessively susceptible to subsequent severe glaucoma and retinal ganglion cell loss, despite maximal efforts to prevent or slow down the disease. Recently, we have shown, in mice and rabbits, that such retinal damage is neither mediated by the alkali itself reaching the retina nor by intraocular pressure elevation. Rather, it is caused by the up-regulation of tumor necrosis factor-α (TNF-α), which rapidly diffuses posteriorly, causing retinal ganglion cell apoptosis and CD45 cell activation. Herein, we investigated the involvement of peripheral blood monocytes and microglia in retinal damage. Using CX3CR1::CCR2 reporter mice and bone marrow chimeras, we show that peripheral CX3CR1CD45CD11bMHC-II monocytes infiltrate into the retina from the optic nerve at 24 hours after the burn and release further TNF-α. A secondary source of peripheral monocyte response originates from a rare population of patrolling myeloid CCR2 cells of the retina that differentiate into CX3CR1 macrophages within hours after the injury. As a result, CX3CR1CD45CD11b microglia become reactive at 7 days, causing further TNF-α release. Prompt TNF-α inhibition after corneal burn suppresses monocyte infiltration and microglia activation, and protects the retina. This study may prove relevant to other injuries of the central nervous system.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2018.03.005},
	author = {Paschalis, Eleftherios I and Lei, Fengyang and Zhou, Chengxin and Kapoulea, Vassiliki and Thanos, Aristomenis and Dana, Reza and Vavvas, Demetrios G and Chodosh, James and Dohlman, Claes H}
}
@article {742296,
	title = {Impact of Storage Temperature on the Expression of Cell Survival Genes in Cultured ARPE-19 Cells.},
	journal = {Curr Eye Res},
	volume = {42},
	number = {1},
	year = {2017},
	pages = {134-144},
	abstract = {PURPOSE: The development of a suitable storage method for retinal pigment epithelium (RPE) is necessary in the establishment of future RPE replacement therapy, and storage temperature has proven to be pivotal for cell survival. ARPE-19, a widely used model for RPE, has been shown to yield the greatest number of viable cells when stored at 16{\textdegree}C compared to other storage temperatures. In this study, we analyze the gene expression profile of cultured ARPE-19 cells after seven days of storage at different temperatures in an effort to predict the gene-level consequences of storage of RPE transplants. MATERIALS AND METHODS: ARPE-19 cells were cultured until confluence and then stored in minimum essential medium at 4{\textdegree}C, 16{\textdegree}C, and 37{\textdegree}C for seven days. The total RNA was isolated and the gene expression profile was determined using DNA microarrays. The Results were validated using qPCR. RESULTS: Principal component and hierarchical clustering analyses show that the gene expression profiles of cell cultures stored at different temperatures cluster into separate groups. Cultures stored at 4{\textdegree}C cluster closest to the control cultures that were not stored and display the least change in gene expression after storage (157 differentially expressed genes). Cultures stored at 16{\textdegree}C and 37{\textdegree}C display a much larger change in differential gene expression (1787 and 1357 differentially expressed genes, respectively). At 16{\textdegree}C, the expression of several genes with proposed tumor suppressor functions was markedly increased. Changes in regulation of several known signaling pathways and of oxidative stress markers were discovered at both 16{\textdegree}C and 37{\textdegree}C, and activation of the angiogenesis marker vascular endothelial growth factor (VEGF) was discovered at 37{\textdegree}C. There was no evidence of the activation of inflammatory processes in stored cell cultures. CONCLUSION: ARPE-19 cultures stored at 16{\textdegree}C show the greatest propensity to modulate their gene expression profile in a manner that supports cell survival during storage.},
	issn = {1460-2202},
	doi = {10.3109/02713683.2016.1145236},
	author = {Pasovic, Lara and Eidet, Jon R and Olstad, Ole K and Chen, Dong F and Lyberg, Torstein and Utheim, Tor P}
}
@article {882966,
	title = {Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study.},
	journal = {Ophthalmology},
	volume = {123},
	number = {11},
	year = {2016},
	month = {2016 Nov},
	pages = {2318-2327},
	abstract = {PURPOSE: Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. DESIGN: Prospective cohort study. PARTICIPANTS: Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. METHODS: By using validated questions, we updated participants{\textquoteright} status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. MAIN OUTCOME MEASURES: During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; >= or \&lt;22 mmHg) or visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Multivariable relative risks (MVRRs) and 95\% confidence intervals (CIs) were estimated. RESULTS: Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95\% CI, 1.06-1.97); in particular, a report within the past 2\&nbsp;years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95\% CI, 1.07-3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes (P for heterogeneity >=0.36), although associations were strongest in relation to the POAG subtypes with IOP \&lt;22 mmHg (MVRR, 1.93; 95\% CI, 1.09-3.43) and early paracentral VF loss (MVRR, 2.27; 95\% CI, 1.32-3.88). CONCLUSIONS: Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG. Because these findings may be due to chance, they need confirmation in larger studies.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.07.014},
	author = {Pasquale, Louis R and Hyman, Leslie and Wiggs, Janey L and Rosner, Bernard A and Joshipura, Kaumudi and McEvoy, Mark and McPherson, Zachary E and Danias, John and Kang, Jae H}
}
@article {1062846,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {124},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {e50-e51},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.10.034},
	author = {Pasquale, Louis R and Hyman, Leslie and Wiggs, Janey L and Rosner, Bernard A and Joshipura, Kaumudi and McEvoy, Mark and McPherson, Zachary E and Danias, John and Kang, Jae H}
}
@article {591251,
	title = {Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {12},
	year = {2015},
	month = {2015 Nov 1},
	pages = {7021-8},
	abstract = {PURPOSE: There is considerable evidence for systemic vascular dysfunction in primary open-angle glaucoma (POAG). We performed nailfold capillary video microscopy to observe directly the nature of nonocular microvasculature abnormalities in POAG. METHODS: We enrolled 199 POAG patients and 124 control subjects from four sites. We used JH-1004 capillaroscopes to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject{\textquoteright}s nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops \&gt; 50 μm, and avascular zones \&gt; 100 μm by graders masked to case status. Multivariable odds ratios (ORs) and 95\% confidence intervals (CIs) for POAG were obtained by means of logistic regression analyses that were applied to data from all cases and controls. Corresponding estimates of moderate or severe POAG versus mild POAG (based on the Hodapp-Anderson-Parrish scale) were obtained among cases only. RESULTS: After controlling for demographic factors, family history of glaucoma, systemic diseases, and use of anticoagulation and antiplatelet therapy, for each 100 nailfold capillaries assessed, all types of microvascular abnormalities were significantly associated with POAG. Specifically, the presence of any dilated capillaries (OR = 2.9; 95\% CI, 1.6-5.6), avascular zones (OR = 4.4; 95\% CI, 1.7-11.3) and hemorrhages (OR = 12.2; 95\% CI, 5.9-25.1) were associated with POAG. Among cases, the frequency of microvascular abnormalities was not associated with glaucoma severity (P >= 0.43). CONCLUSIONS: These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-17860},
	author = {Pasquale, Louis R and Hanyuda, Akiko and Ren, Ai and Giovingo, Michael and Greenstein, Scott H and Cousins, Clara and Patrianakos, Thomas and Tanna, Angelo P and Wanderling, Christopher and Norkett, William and Wiggs, Janey L and Green, Kelsey and Kang, Jae H and Knepper, Paul A}
}
@article {1363177,
	title = {The blue arc entoptic phenomenon in glaucoma (an American ophthalmological thesis)},
	journal = {Trans Am Ophthalmol Soc},
	volume = {111},
	year = {2013},
	month = {2013 Sep},
	pages = {46-55},
	abstract = {PURPOSE: To determine whether the blue arc entoptic phenomenon, a positive visual response originating from the retina with a shape that conforms to the topology of the nerve fiber layer, is depressed in glaucoma. METHODS: We recruited a cross-sectional, nonconsecutive sample of 202 patients from a single institution in a prospective manner. Subjects underwent full ophthalmic examination, including standard automated perimetry (Humphrey Visual Field 24-2) or frequency doubling technology (Screening C 20-5) perimetry. Eligible patients viewed computer-generated stimuli under conditions chosen to optimize perception of the blue arcs. Unmasked testers instructed patients to report whether they were able to perceive blue arcs but did not reveal what response was expected. We created multivariable logistic regression models to ascertain the demographic and clinical parameters associated with perceiving the blue arcs. RESULTS: In multivariable analyses, each 0.1 unit increase in cup-disc ratio was associated with 36\% reduced likelihood of perceiving the blue arcs (odds ratio [OR] = 0.66 [95\% confidence interval (CI): 0.53-0.83], P\&lt;.001). A smaller mean defect was associated with an increased likelihood of perceiving the blue arcs (OR=1.79 [95\% CI: 1.40-2.28]); P\&lt;.001), while larger pattern standard deviation (OR=0.72 [95\% CI: 0.57-0.91]; P=.005) and abnormal glaucoma hemifield test (OR=0.25 [0.10-0.65]; P=.006) were associated with a reduced likelihood of perceiving them. Older age and media opacity were also associated with an inability to perceive the blue arcs. CONCLUSION: In this study, the inability to perceive the blue arcs correlated with structural and functional features associated with glaucoma, although older age and media opacity were also predictors of this entoptic response.},
	keywords = {Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Glaucoma, Humans, Male, Middle Aged, Multivariate Analysis, Photic Stimulation, Prospective Studies, Visual Field Tests, Visual Perception},
	issn = {1545-6110},
	author = {Pasquale, Louis R and Brusie, Steven}
}
@article {1748511,
	title = {Metabolite and Lipid Biomarkers Associated With Intraocular Pressure and Inner Retinal Morphology: 1H NMR Spectroscopy Results From the UK Biobank},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {11},
	year = {2023},
	month = {2023 Aug 01},
	pages = {11},
	abstract = {PURPOSE: The purpose of this study was to assess metabolites associated with intraocular pressure (IOP) and inner retina structure. METHODS: We cross-sectionally assessed 168 non-fasting plasma metabolites measured by nuclear magnetic resonance (NMR) spectroscopy with IOP (n = 28,195), macular retinal nerve fiber layer thickness (mRNFL; n = 10,584), and macular ganglion cell inner plexiform layer thickness (mGCIPL; n = 10,554) in the UK Biobank. We used multiple linear regression models adjusting for various covariates with probit-transformed metabolite levels as predictors for each outcome. Each estimate represents the difference in outcome variable per standard deviation increase in the probit-transformed metabolite values. We used the number of effective (NEF) tests and false discovery rate (FDR) to adjust for multiple comparisons for metabolites and metabolite classes, respectively. RESULTS: In individual metabolite analysis, multiple amino acids, especially branched-chain amino acids, were associated with lower IOP (-0.12 mm Hg; 95\% confidence interval = -0.16 to -0.07; NEF = 2.7E-05). Albumin, 3 hydroxybutyrate, lactate, and several lipids were associated with higher IOP (range = 0.07 to 0.18 mm Hg, NEF = <= 0.039). In IOP-adjusted analyses, five HDL-related metabolites were associated with thinner mRNFL (-0.15 microns for all metabolites, NEF = <= 0.027), whereas five LDL-related metabolites were associated with thicker mGCIPL (range = 0.17 to 0.20 microns; NEF = <= 0.044). In metabolite class analysis, the lipid components of lipoproteins (cholesterol, triglycerides, etc.) were not associated with our outcomes (FDR \&gt; 0.2 for all); yet multiple lipoproteins were significantly (FDR \&lt; 0.05) associated with all outcomes. CONCLUSIONS: Branched-chain amino acids were associated with lower IOP, HDL metabolites were associated with thinner mRNFL, and LDL metabolites were associated with thicker mGCIPL.},
	keywords = {Biological Specimen Banks, Intraocular Pressure, Lipids, Nerve Fibers, Retina, Retinal Ganglion Cells, Tomography, Optical Coherence, United Kingdom},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.11.11},
	author = {Pasquale, Louis R and Khawaja, Anthony P and Wiggs, Janey L and Kim, Jihye and Hysi, Pirro and Tobias Elze and Lasky-Su, Jessica and Kang, Jae H and Zeleznik, Oana and UK Biobank Eye and Vision Consortium}
}
@article {603856,
	title = {Exfoliation syndrome: assembling the puzzle pieces.},
	journal = {Acta Ophthalmol},
	volume = {94},
	number = {6},
	year = {2016},
	month = {2016 Sep},
	pages = {e505-12},
	abstract = {PURPOSE: To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. METHODS: The highlights of three categories of talks on cutting edge research in the field were summarized. RESULTS: Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms. CONCLUSION: Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and ex\&nbsp;vivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to {\textquoteright}upstream solutions{\textquoteright} to reduce the ocular morbidity produced by XFS.},
	issn = {1755-3768},
	doi = {10.1111/aos.12918},
	author = {Pasquale, Louis R and Borr{\'a}s, Terete and Fingert, John H and Wiggs, Janey L and Ritch, Robert}
}
@article {1363178,
	title = {CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States},
	journal = {Am J Ophthalmol},
	volume = {155},
	number = {2},
	year = {2013},
	month = {2013 Feb},
	pages = {342-353.e5},
	abstract = {PURPOSE: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients.

DESIGN: Retrospective observational case series.

METHODS: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results.

RESULTS: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95\% CI: -0.08, -0.03; P~= 6.23E-05) despite having higher intraocular pressure (IOP) (0.70~mm Hg higher per G allele at DNA collection; 95\% CI: 0.40, 1.00; P~= 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95\% CI: 0.02, 0.07; P~= 4.74E-04) despite having lower IOP (-0.57~mm Hg per A allele at DNA collection; 95\% CI: -0.84, -0.29; P~= 6.55E-05).

CONCLUSION: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic~nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.},
	keywords = {Adult, Aged, Aged, 80 and over, Alleles, Chromosomes, Human, Pair 9, Female, Genotype, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Middle Aged, Optic Disk, Optic Nerve Diseases, Phenotype, Polymorphism, Single Nucleotide, Retrospective Studies, RNA, Long Noncoding, Trabeculectomy, United States, Visual Fields},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2012.07.023},
	author = {Pasquale, Louis R and Loomis, Stephanie J and Kang, Jae H and Yaspan, Brian L and Abdrabou, Wael and Budenz, Donald L and Chen, Teresa C and Delbono, Elizabeth and Friedman, David S and Gaasterland, Douglas and Gaasterland, Terry and Grosskreutz, Cynthia L and Lee, Richard K and Lichter, Paul R and Liu, Yutao and McCarty, Catherine A and Moroi, Sayoko E and Olson, Lana M and Realini, Tony and Rhee, Douglas J and Schuman, Joel S and Singh, Kuldev and Vollrath, Douglas and Wollstein, Gadi and Zack, Donald J and Allingham, R Rand and Pericak-Vance, Margaret A and Weinreb, Robert N and Zhang, Kang and Hauser, Michael A and Richards, Julia E and Haines, Jonathan L and Wiggs, Janey L}
}
@article {1323938,
	title = {LOXL1 Polymorphisms: Genetic Biomarkers that Presage Environmental Determinants of Exfoliation Syndrome},
	journal = {J Glaucoma},
	volume = {27 Suppl 1},
	year = {2018},
	month = {2018 Jul},
	pages = {S20-S23},
	abstract = {An agnostic high throughput search of the genome revealed a robust association between LOXL1 genetic polymorphisms and exfoliation syndrome (XFS), a discovery that likely would not have been possible with candidate or family-based gene search strategies. While questions remain regarding how LOXL1 gene variants contribute to XFS pathogenesis, it is clear that the frequencies of disease-related alleles do not track with the varying disease burden throughout the world, prompting a search for environmental risk factors. A geo-medicine approach revealed that disease load seemed to increase as a function of the distance from the equator. The exact reason for this extraequatorial disease distribution pattern remains unclear, but a greater amount of time spent outdoors is a robust risk factor for XFS, suggesting climatic factors such as ocular solar exposure and colder ambient temperature may be involved in disease pathogenesis. Prospective studies have also implicated higher coffee consumption and lower dietary folate intake in association with incident XFS. The discovery of environmental risk factors for XFS suggests that preventive measures may help to reduce ocular morbidity from XFS.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000915},
	author = {Pasquale, Louis R and Kang, Jae Hee and Fan, Bao Jian and Levkovitch-Verbin, Hani and Wiggs, Janey L}
}
@article {1363179,
	title = {Estrogen pathway polymorphisms in relation to primary open angle glaucoma: an analysis accounting for gender from the United States},
	journal = {Mol Vis},
	volume = {19},
	year = {2013},
	month = {2013},
	pages = {1471-81},
	abstract = {PURPOSE: Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender. METHODS: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) >=22\&nbsp;mmHg (high-pressure glaucoma [HPG]) or IOP \&lt;22\&nbsp;mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women. RESULTS: Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p\&lt;0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p\&gt;0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p<=0.001) and NPG (permuted gene p=0.01). CONCLUSIONS: The estrogen SNP pathway was associated with POAG among women.},
	keywords = {Case-Control Studies, Estrogens, Female, Genetic Predisposition to Disease, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Sex Characteristics, Signal Transduction, United States},
	issn = {1090-0535},
	author = {Pasquale, Louis R and Loomis, Stephanie J and Weinreb, Robert N and Kang, Jae H and Yaspan, Brian L and Bailey, Jessica Cooke and Gaasterland, Douglas and Gaasterland, Terry and Lee, Richard K and Scott, William K and Lichter, Paul R and Budenz, Donald L and Liu, Yutao and Realini, Tony and Friedman, David S and McCarty, Catherine A and Moroi, Sayoko E and Olson, Lana and Schuman, Joel S and Singh, Kuldev and Vollrath, Douglas and Wollstein, Gadi and Zack, Donald J and Brilliant, Murray and Sit, Arthur J and Christen, William G and Fingert, John and Kraft, Peter and Zhang, Kang and Allingham, R Rand and Pericak-Vance, Margaret A and Richards, Julia E and Hauser, Michael A and Haines, Jonathan L and Wiggs, Janey L}
}
@article {1608604,
	title = {Development of Primary Open Angle Glaucoma-Like Features in a Rhesus Macaque Colony From Southern China},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {9},
	year = {2021},
	month = {2021 Aug 02},
	pages = {20},
	abstract = {Purpose: To describe the ocular phenotype of spontaneous glaucoma in a non-human primate colony. Methods: In total, 722 Rhesus macaque monkeys aged 10 to 25 years underwent optical coherence tomography (OCT), fundus photography (FP), and intraocular pressure (IOP) measurements. Monkeys with baseline cup-to-disc ratio (CDR) \&lt;0.5 were used to establish baseline ocular features. A subset was followed longitudinally for three years and compared to glaucoma suspects on the basis of OCT/FP criteria. Results: The average IOP under ketamine sedation and average CDR for the entire colony was 13.0 {\textpm} 4.3 mm Hg and 0.38 {\textpm} 0.07, respectively. The mean baseline conscious IOP of glaucoma suspects (N = 18) versus controls (N = 108) was 16.2 {\textpm} 3.5 mm Hg and 13.9 {\textpm} 2.3 mm Hg, respectively (P = 0.001). All glaucoma suspects had unremarkable slit lamp examinations and open angles based on anterior segment OCT. Baseline global circumpapillary retinal nerve fiber layer (RNFL) thickness was 91.5 {\textpm} 11.0 {\textmu}M versus 102.7 {\textpm} 8.5 {\textmu}M in suspects and controls, respectively (P \&lt; 0.0001). All sectors on the baseline circumpapillary OCT showed a significant reduction in RNFL thickness versus controls (P <= 0.0022) except for the temporal sector (P >= 0.07). In three-year longitudinal analysis, neither CDR nor OCT parameters changed in controls (N = 40; P >= 0.16), whereas significant increase in CDR (P = 0.018) and nominally significant decreases in two OCT sectors (nasal, P = 0.023 and nasal inferior, P = 0.046) were noted in suspects. Conclusions: Members of a nonhuman primate colony exhibit important ophthalmic features of human primary open-angle glaucoma. Translational Relevance: Identification of a spontaneous model of glaucoma in nonhuman primates represents an unprecedented opportunity to elucidate the natural history, pathogenesis and effective therapeutic strategies for the disease.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.9.20},
	author = {Pasquale, Louis R and Gong, Li and Wiggs, Janey L and Pan, Lingzhen and Yang, Zhenyan and Wu, Mingling and Yang, Zunyuan and Chen, Dong Feng and Zeng, Wen}
}
@article {931136,
	title = {Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample},
	journal = {Menopause},
	volume = {24},
	number = {2},
	year = {2017},
	month = {2017 Feb},
	pages = {150-156},
	abstract = {OBJECTIVE: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. METHODS: Using data from the Nurses{\textquoteright} Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. RESULTS: The genetic risk score was associated with self-reported ANM (P = 2.2 {\texttimes} 10) and predicted 4.8\% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95\% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P >=0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95\% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95\% CI: 0.72, 1.69; P = 0.65, respectively). CONCLUSIONS: A genetic risk score predicting 4.8\% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.},
	issn = {1530-0374},
	doi = {10.1097/GME.0000000000000741},
	author = {Pasquale, Louis R and Aschard, Hugues and Kang, Jae H and Bailey, Jessica N Cooke and Lindstr{\"o}m, Sara and Chasman, Daniel I and Christen, William G and Allingham, R Rand and Ashley-Koch, Allison and Lee, Richard K and Moroi, Sayoko E and Brilliant, Murray H and Wollstein, Gadi and Schuman, Joel S and Fingert, John and Budenz, Donald L and Realini, Tony and Gaasterland, Terry and Gaasterland, Douglas and Scott, William K and Singh, Kuldev and Sit, Arthur J and Igo, Robert P and Song, Yeunjoo E and Hark, Lisa and Ritch, Robert and Rhee, Douglas J and Gulati, Vikas and Havens, Shane and Vollrath, Douglas and Zack, Donald J and Medeiros, Felipe and Weinreb, Robert N and Pericak-Vance, Margaret A and Liu, Yutao and Kraft, Peter and Richards, Julia E and Rosner, Bernard A and Hauser, Michael A and Haines, Jonathan L and Wiggs, Janey L}
}
@article {280886,
	title = {Solar exposure and residential geographic history in relation to exfoliation syndrome in the United States and Israel.},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {12},
	year = {2014},
	month = {2014 Dec 1},
	pages = {1439-45},
	abstract = {IMPORTANCE: Residential (geographic) history and extent of solar exposure may be important risk factors for exfoliation syndrome (XFS) but, to our knowledge, detailed lifetime solar exposure has not been previously evaluated in XFS. OBJECTIVE: To assess the relation between residential history, solar exposure, and XFS. DESIGN, SETTING, AND PARTICIPANTS: This clinic-based case-control study was conducted in the United States and Israel. It involved XFS cases and control individuals (all >=60-year-old white individuals) enrolled from 2010 to 2012 (United States: 118 cases and 106 control participants; Israel: 67 cases and 72 control participants). MAIN OUTCOMES AND MEASURES: Weighted lifetime average latitude of residence and average number of hours per week spent outdoors as determined by validated questionnaires. RESULTS: In multivariable analyses, each degree of weighted lifetime average residential latitude away from the equator was associated with 11\% increased odds of XFS (pooled odds ratio [OR], 1.11; 95\% CI, 1.05-1.17; P \&lt; .001). Furthermore, every hour per week spent outdoors during the summer, averaged over a lifetime, was associated with 4\% increased odds of XFS (pooled OR, 1.04; 95\% CI, 1.00-1.07; P = .03). For every 1\% of average lifetime summer time between 10 am and 4 pm that sunglasses were worn, the odds of XFS decreased by 2\% (OR, 0.98; 95\% CI, 0.97-0.99; P \&lt; .001) in the United States but not in Israel (OR, 1.00; 95\% CI, 0.99-1.01; P = .92; P for heterogeneity = .005). In the United States, after controlling for important environmental covariates, history of work over water or snow was associated with increased odds of XFS (OR, 3.86; 95\% CI, 1.36-10.9); in Israel, there were too few people with such history for analysis. We did not identify an association between brimmed hat wear and XFS (P \&gt; .57). CONCLUSIONS AND RELEVANCE: Lifetime outdoor activities may contribute to XFS. The association with work over snow or water and the lack of association with brimmed hat wear suggests that ocular exposure to light from reflective surfaces may be an important type of exposure in XFS etiology.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.3326},
	author = {Pasquale, Louis R and Jiwani, Aliya Z and Zehavi-Dorin, Tzukit and Majd, Arow and Rhee, Douglas J and Chen, Teresa and Turalba, Angela and Shen, Lucy and Brauner, Stacey and Grosskreutz, Cynthia and Gardiner, Matthew and Chen, Sherleen and Borboli-Gerogiannis, Sheila and Greenstein, Scott H and Chang, Kenneth and Ritch, Robert and Loomis, Stephanie and Kang, Jae H and Wiggs, Janey L and Levkovitch-Verbin, Hani}
}
@article {303881,
	title = {Prospects for gene-environment interactions in exfoliation syndrome.},
	journal = {J Glaucoma},
	year = {2014},
	month = {2014 Oct-Nov},
	pages = {S64-7},
	abstract = {Complex traits can be triggered by environmental factors in genetically predisposed individuals. The lysyl oxidase-like 1 gene (LOXL1) variants associated with exfoliation syndrome (XFS) are detected in \&gt;90\% of cases that have been genotyped from sites around the world. Remarkably, roughly 80\% of people without XFS also possess these same variants in all populations that have been tested. Nonetheless, the prevalence of XFS varies from <=0.4\% to \&gt;20\%. These data suggest that other genetic variants, epigenetic modifications, or environmental factors also contribute to XFS. Furthermore, it is possible that environmental factors modify the association between LOXL1 and XFS. Interactions between LOXL1 variants and environmental factors could explain the varying prevalence of XFS seen throughout the world. At the very least, the discovery of the association between LOXL1 variants and XFS has opened the door to the discovery of environmental risk factors for this condition. Candidate gene-environment interactions in XFS will be discussed.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000113},
	author = {Pasquale, Louis R and Kang, Jae H and Wiggs, Janey L}
}
@article {1814391,
	title = {Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration},
	journal = {Cell Rep},
	volume = {43},
	number = {3},
	year = {2024},
	month = {2024 Mar 26},
	pages = {113931},
	abstract = {In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to β-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q-/- or C3-/-, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration.},
	keywords = {Animals, Axons, beta-Glucans, Mammals, Nerve Regeneration, Neutrophils, Optic Nerve Injuries, Retinal Ganglion Cells},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2024.113931},
	author = {Passino, Ryan and Finneran, Matthew C and Hafner, Hannah and Feng, Qian and Huffman, Lucas D and Zhao, Xiao-Feng and Johnson, Craig N and Kawaguchi, Riki and Oses-Prieto, Juan A and Burlingame, Alma L and Geschwind, Daniel H and Benowitz, Larry I and Giger, Roman J}
}
@article {1460370,
	title = {MAGEL2-related disorders: A study and case series},
	journal = {Clin Genet},
	volume = {96},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {493-505},
	abstract = {Pathogenic MAGEL2 variants result in the phenotypes of Chitayat-Hall syndrome (CHS), Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). We present five patients with mutations in MAGEL2, including the first patient reported with a missense variant, adding to the limited literature. Further, we performed a systematic review of the CHS and SYS literature, assess the overlap between CHS, SYS and PWS, and analyze genotype-phenotype correlations among them. We conclude that there is neither a clinical nor etiological difference between CHS and SYS, and propose that the two syndromes simply be referred to as MAGEL2-related disorders.},
	issn = {1399-0004},
	doi = {10.1111/cge.13620},
	author = {Patak, Jameson and Gilfert, James and Byler, Melissa and Neerukonda, Vamsee and Thiffault, Isabelle and Cross, Laura and Amudhavalli, Shivarajan and Pacio-Miguez, Marta and Palomares-Bralo, Maria and Garcia-Minaur, Sixto and Santos-Simarro, Fernando and Powis, Zoe and Alcaraz, Wendy and Tang, Sha and Jurgens, Julie and Barry, Brenda and England, Eleina and Engle, Elizabeth and Hess, Jonathon and Lebel, Robert R}
}
@article {1698236,
	title = {Deep Learning Using Preoperative AS-OCT Predicts Graft Detachment in DMEK},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {5},
	year = {2023},
	month = {2023 May 01},
	pages = {14},
	abstract = {PURPOSE: To evaluate a novel deep learning algorithm to distinguish between eyes that may or may not have a graft detachment based on pre-Descemet membrane endothelial keratoplasty (DMEK) anterior segment optical coherence tomography (AS-OCT) images. METHODS: Retrospective cohort study. A multiple-instance learning artificial intelligence (MIL-AI) model using a ResNet-101 backbone was designed. AS-OCT images were split into training and testing sets. The MIL-AI model was trained and validated on the training set. Model performance and heatmaps were calculated from the testing set. Classification performance metrics included F1 score (harmonic mean of recall and precision), specificity, sensitivity, and area under curve (AUC). Finally, MIL-AI performance was compared to manual classification by an experienced ophthalmologist. RESULTS: In total, 9466 images of 74 eyes (128 images per eye) were included in the study. Images from 50 eyes were used to train and validate the MIL-AI system, while the remaining 24 eyes were used as the test set to determine its performance and generate heatmaps for visualization. The performance metrics on the test set (95\% confidence interval) were as follows: F1 score, 0.77 (0.57-0.91); precision, 0.67 (0.44-0.88); specificity, 0.45 (0.15-0.75); sensitivity, 0.92 (0.73-1.00); and AUC, 0.63 (0.52-0.86). MIL-AI performance was more sensitive (92\% vs. 31\%) but less specific (45\% vs. 64\%) than the ophthalmologist{\textquoteright}s performance. CONCLUSIONS: The MIL-AI predicts with high sensitivity the eyes that may have post-DMEK graft detachment requiring rebubbling. Larger-scale clinical trials are warranted to validate the model. TRANSLATIONAL RELEVANCE: MIL-AI models represent an opportunity for implementation in routine DMEK suitability screening.},
	keywords = {Artificial Intelligence, Corneal Diseases, Deep Learning, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Humans, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.5.14},
	author = {Patefield, Alastair and Meng, Yanda and Airaldi, Matteo and Coco, Giulia and Vaccaro, Sabrina and Parekh, Mohit and Semeraro, Francesco and Gadhvi, Kunal A and Kaye, Stephen B and Zheng, Yalin and Romano, Vito}
}
@article {1363183,
	title = {Paraneoplastic dermatomyositis related to a chondrosarcoma involving the cavernous sinus},
	journal = {J Neuroophthalmol},
	volume = {33},
	number = {4},
	year = {2013},
	month = {2013 Dec},
	pages = {363-6},
	abstract = {Approximately one third of all cases of dermatomyositis may be associated with malignancy. We describe a patient with unexplained rash, joint pain, and muscle weakness, who subsequently developed a cavernous sinus syndrome due to a central nervous system chondrosarcoma. Discovery of this tumor and further dermatologic evaluation, including skin biopsy, resulted in diagnosis of paraneoplastic dermatomyositis due to cavernous sinus chondrosarcoma.},
	keywords = {Bone Neoplasms, Cavernous Sinus, Chondrosarcoma, Dermatomyositis, Female, Humans, Magnetic Resonance Imaging, Middle Aged},
	issn = {1536-5166},
	doi = {10.1097/WNO.0b013e3182a30480},
	author = {Patel, Mrinali M and Stacy, Rebecca C}
}
@article {1363180,
	title = {Fundus autofluorescence in ampiginous choroiditis},
	journal = {Ophthalmic Surg Lasers Imaging Retina},
	volume = {44},
	number = {4},
	year = {2013},
	month = {2013 Jul-Aug},
	pages = {393-7},
	abstract = {Fundus autofluorescence (FAF) is being increasingly employed in the evaluation of retinal diseases. We report the first description of FAF findings during the natural history of ampiginous choroiditis and correlate these findings to fundus photography, infrared imaging, and cross-sectional optical coherence tomography. In a patient with a 12-month recurring, relapsing course of ampiginous choroiditis, there was a predictable pattern of FAF findings. At the time of presentation with a whitish-yellow, creamy clinical lesion, FAF reveals a diffuse, subtle hyperautofluorescence at the site of activity. As the clinical lesion fades, the FAF takes on a more intense, discrete, coalesced hyperautofluorescence, which decreases and becomes stippled over time, eventually giving way to a patch of hypoautofluorescence at the site of inactivity. Examination over the patient{\textquoteright}s long course suggests that FAF evolves predictably during exacerbations and remissions, and the FAF findings reveal activity well after the clinical lesion resolves. FAF is a simple, noninvasive, and effective modality for following the evolution of ampiginous choroiditis.},
	keywords = {Adult, Choroiditis, Chronic Disease, Female, Fluorescein Angiography, Fundus Oculi, Humans, Recurrence},
	issn = {2325-8179},
	doi = {10.3928/23258160-20130715-10},
	author = {Patel, Mrinali and Vavvas, Demetrios G}
}
@article {313096,
	title = {Spontaneous resolution of a postvitrectomy macular hole retinal detachment.},
	journal = {Retin Cases Brief Rep},
	volume = {8},
	number = {3},
	year = {2014},
	month = {2014 Summer},
	pages = {161-3},
	abstract = {PURPOSE: The purpose of this report was to describe a case of spontaneous resolution of a large postvitrectomy macular hole retinal detachment. METHODS: Case report and optical coherence tomography imaging. RESULTS: A 64-year-old man with history of macula-off retinal detachment and 4 previous vitrectomies in the left eye developed a macular hole and associated retinal detachment 3 months after his last vitreoretinal surgery. Two months later, examination revealed that the macular hole had spontaneously closed, and the retinal detachment had resolved. CONCLUSION: Spontaneous resolution of macular hole-associated retinal detachment in a previously vitrectomized eye has not been reported previously. Changes in tangential traction by the associated epiretinal membrane, improvement of the cystoid changes noted at the edge of the macular hole, and/or proliferation of glial tissue to bridge the hole, along with the absorption of the subretinal fluid by the retinal pigment epithelium pump contributed to this rare event have been hyphothesized.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000052},
	author = {Patel, Mrinali and Vavvas, Demetrios G}
}
@article {503936,
	title = {Under the Guise of Retinitis.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {10},
	year = {2015},
	month = {2015 Oct 1},
	pages = {1205-6},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.1926},
	author = {Patel, Avni V and Papakostas, Thanos D and Vavvas, Demetrios G}
}
@article {1603878,
	title = {Acute Benign Paroxysmal Positional Vertigo After Endothelial Keratoplasty-A Unique Cause of Postoperative Nausea and Headache},
	journal = {Cornea},
	volume = {40},
	number = {7},
	year = {2021},
	month = {2021 Jul 01},
	pages = {926-929},
	abstract = {PURPOSE: To describe a case of new-onset benign paroxysmal positional vertigo (BPPV) after uncomplicated Descemet stripping automated endothelial keratoplasty. METHODS: Case report and review of literature. RESULTS: A 61-year-old woman with a history of steroid-induced glaucoma and penetrating keratoplasty for Fuchs endothelial dystrophy, and no history of BPPV or other vertigo, underwent Descemet stripping automated endothelial keratoplasty for penetrating keratoplasty graft failure. On the third postoperative day, she developed acute spinning vertigo, nausea, and headache on sitting up after 3 days of strict supine positioning. Her ophthalmic examination was benign, with no evidence of a pupillary block, and she was diagnosed by an otologist with BPPV. Her symptoms resolved after 1 week without further intervention. CONCLUSIONS: BPPV is a benign but rare complication of nonotologic surgery and has not been previously reported with ophthalmic surgery. The overlap in symptomatology between BPPV and other serious and potentially vision-threatening causes of postoperative nausea and headache, such as pupillary block glaucoma, makes this a relevant etiology to consider in the spectrum of postendothelial keratoplasty complications.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002587},
	author = {Patel, Sachin and Yuan, Amy and Pineda, Roberto}
}
@article {591221,
	title = {Visual Outcomes after Proton Beam Irradiation for Choroidal Melanomas Involving the Fovea.},
	journal = {Ophthalmology},
	volume = {123},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {369-77},
	abstract = {PURPOSE: To report visual outcomes in patients undergoing proton beam irradiation of tumors located within 1 disc diameter of the fovea. DESIGN: Retrospective review. PARTICIPANTS: Patients with choroidal melanoma involving the fovea treated with proton beam therapy between 1975 and\&nbsp;2009. METHODS: Three hundred fifty-one patients with choroidal melanomas located 1 disc diameter (DD) or less from the fovea and more than 1 DD away from the optic nerve were included in this study. In a subgroup of 203 of the patients with small and medium choroidal melanomas, the effect of a reduced dose of radiation, 50 Gy (relative biological effectiveness [RBE]) versus 70 Gy (RBE), on visual outcomes was analyzed. The Kaplan-Meier method and Cox regression analysis were performed to calculate cumulative rates of vision loss and to assess risk factors for vision loss, respectively. MAIN OUTCOME MEASURES: Visual acuity and radiation complications, which included radiation maculopathy, papillopathy, retinal detachment, and rubeosis, were assessed. RESULTS: Three hundred fifty-one patients were included in this study with a mean follow-up time of 68.7 months. More than one-third of patients (35.5\%) retained 20/200 or better vision 5 years after proton beam irradiation. For those patients with a baseline visual acuity of 20/40 or better, 16.2\% of patients retained this level of vision 5 years after proton beam irradiation. Tumor height less than 5 mm and baseline visual acuity 20/40 or better were associated significantly with a better visual outcome (P \&lt; 0.001). More than two-thirds (70.4\%) of patients receiving 50 Gy (RBE) and nearly half (45.1\%) of patients receiving 70 Gy (RBE) retained 20/200 or better vision 5 years after treatment, but this difference was not significant. Approximately 20\% of patients with these smaller macular tumors retained 20/40 vision or better 5 years after irradiation. CONCLUSIONS: The results of this retrospective analysis demonstrate that despite receiving a full dose of radiation to the fovea, many patients with choroidal melanoma with foveal involvement maintain useful vision. A radiation dose reduction from 70 to 50 Gy (RBE) did not seem to increase the proportion of patients who retain usable vision.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.09.031},
	author = {Patel, Avni V and Lane, Anne Marie and Morrison, Margaux A and Trofimov, Alexei V and Shih, Helen A and Gragoudas, Evangelos S and Kim, Ivana K}
}
@article {1658649,
	title = {Comparison in Retreatments between Bevacizumab and Ranibizumab Intravitreal Injections for Retinopathy of Prematurity: A Multicenter Study},
	journal = {Ophthalmology},
	volume = {130},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {373-378},
	abstract = {PURPOSE: To compare the types and dosages of anti-vascular endothelial growth factors (VEGFs) to ascertain whether specific dosages or types of injection were associated with retreatment in clinical practice in the United States. DESIGN: Multicenter, retrospective, consecutive series. PARTICIPANTS: Patients with retinopathy of prematurity (ROP) treated with anti-VEGF injections from 2007 to\&nbsp;2021. METHODS: Sixteen sites from the United States participated. Data collected included demographics, birth characteristics, examination findings, type and dose of anti-VEGF treatment, retreatment rates, and time to retreatment. Comparisons of retreatment rates between bevacizumab and ranibizumab intravitreal injections were made. MAIN OUTCOME MEASURES: Relative rate of retreatment between varying types of anti-VEGF therapy, including bevacizumab and ranibizumab, and the various dosages used for each. RESULTS: Data from 873 eyes of 661 patients (61\% male and 39\% female) were collected. After exclusion of 40 eyes treated with laser before anti-VEGF injection and 266 eyes re-treated with laser at or beyond 8 weeks after the initial anti-VEGF treatment, 567 eyes of 307 patients (63\% male and 37\% female) remained and were included in the primary analysis. There was no difference between the no retreatment and retreatment groups in terms of birthweight, gestational age, age at first injection, ROP stages, or number of involved clock hours. The retreatment group had a larger percentage of aggressive ROP (34\% vs. 18\%, P \&lt; 0.001) and greater percentage of zone 1 ROP (49 vs. 34\%, P\&nbsp;= 0.001) than the no retreatment group. Ranibizumab use was associated with a higher rate of retreatment than bevacizumab use (58\% vs. 37\%, P \&lt; 0.001), whereas the rate of retreatment was not associated with a specific dose of ranibizumab (R2\&nbsp;= 0.67, P\&nbsp;= 0.32). Meanwhile, lower doses of bevacizumab were associated with higher rates of retreatment compared with the higher doses (R2\&nbsp;= 0.84, P\&nbsp;= 0.01). There was a dose-specific trend with higher doses trending toward lower retreatments for bevacizumab. CONCLUSIONS: In a multicenter study of ROP patients initially treated with anti-VEGF therapy, ranibizumab and lower-dose bevacizumab use were associated with an increased rate of retreatment when compared with higher-dose bevacizumab. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Female, Gestational Age, Humans, Infant, Newborn, Intravitreal Injections, Male, Ranibizumab, Retinopathy of Prematurity, Retrospective Studies, Vascular Endothelial Growth Factor A},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.11.012},
	author = {Patel, Nimesh A and Acaba-Berrocal, Luis A and Hoyek, Sandra and Fan, Kenneth C and Martinez-Castellanos, Maria Ana and Baumal, Caroline R and Harper, C Armitage and Berrocal, Audina M and Retinopathy of Prematurity Injection Consortium (ROPIC)}
}
@article {1363181,
	title = {Intraorbital metastasis from solitary fibrous tumor},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {3},
	year = {2013},
	month = {2013 May-Jun},
	pages = {e76-9},
	abstract = {Solitary fibrous tumor (SFT) is a rare spindle cell tumor of mesenchymal origin that usually arises from pleura or pericardium but can also arise from many extraserosal sites. Although more than 50 cases of primary SFT of the orbit have been reported, there are no reports to date of a malignant nonophthalmic SFT metastasizing in the orbital soft tissues (although sphenoid wing bony involvement has been reported). The authors report here the first case of a patient with intraorbital metastasis of a CD34-positive malignant SFT. The patient was a 57-year-old man with a history of malignant pleural SFT and a prior kidney metastasis. He presented with the rapid appearance of proptosis and massive conjunctival chemosis preventing eyelid closure, and he was found to have a well-circumscribed metastasis to his lateral rectus muscle. Surgical excision cured his ocular symptoms, although he died 3 months later from brain and widespread metastases.},
	keywords = {Antigens, CD34, Antineoplastic Agents, Biomarkers, Tumor, Combined Modality Therapy, Fatal Outcome, Humans, Kidney Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Ophthalmologic Surgical Procedures, Orbital Neoplasms, Pleural Neoplasms, Proto-Oncogene Proteins c-bcl-2, Solitary Fibrous Tumor, Pleural},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e318272f311},
	author = {Patel, Mrinali M and Jakobiec, Frederick A and Zakka, Fouad R and Du, Rose and Annino, Donald J and Borboli-Gerogiannis, Sheila and Daniels, Anthony B}
}
@article {1677641,
	title = {Intraocular Lens Exchange: Indications, Comparative Outcomes by Technique, and Complications},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {941-951},
	abstract = {PURPOSE: To describe the indications, outcomes, and complications associated with intraocular lens (IOL) exchange. PATIENTS AND METHODS: To determine the relative frequency of postoperative complications between techniques for all patients undergoing IOL exchange from May 1, 2014 through August 31, 2020. RESULTS: IOL exchange was performed in 511 eyes of 489 patients (59.7\% men; mean age: 67.0 {\textpm} 13.9 years, median time from cataract procedure to IOL exchange: 47.5 months). Mean uncorrected visual acuity significantly improved from 20/192 Snellen equivalent (logMAR 0.981) preoperatively to 20/61 (logMAR 0.487) at last follow-up (P \&lt; 0.001). Overall, 384 eyes (78.7\%) met their desired refractive outcome within {\textpm}1.0 diopter (D). The most frequent complication was cystoid macular edema (CME) (n=39, 7.6\%). Iris-sutured technique was associated with significantly greater frequency of subsequent IOL dislocation (10.3\%) than 4-point scleral sutured (0\%, P = 0.002), anterior chamber IOL (ACIOL, 1.5\%, P = 0.01), and 2-point scleral sutured (0\%, P = 0.03) techniques. Yamane scleral-fixation technique was associated with significantly greater frequency of developing IOL tilt (11.8\%) than ACIOL (0\%, P = 0.002), 4-point scleral sutured (1.1\%, P = 0.01), 2-point scleral sutured (0\%, P = 0.04), and iris-sutured (0\%, P = 0.04) techniques. CONCLUSION: IOL exchange significantly improved uncorrected visual acuity and more than three-quarters of eyes met the refractive goal. Certain techniques were associated with complications, including subsequent dislocation associated with iris-sutured technique and IOL tilt associated with Yamane scleral-fixation technique. This information may help guide surgeons in deciding between procedural techniques for individual patients during IOL exchange preoperative planning.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S399857},
	author = {Patel, Veshesh and Pakravan, Parastou and Lai, James and Watane, Arjun and Mehra, Divy and Eatz, Tiffany Alyssa and Patel, Nimesh and Yannuzzi, Nicolas A and Sridhar, Jayanth}
}
@article {1817226,
	title = {A Cost-Effectiveness Analysis of Pegcetacoplan for the Treatment of Geographic Atrophy},
	journal = {Ophthalmol Retina},
	volume = {8},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {25-31},
	abstract = {PURPOSE: To evaluate the cost-effectiveness of the treatment of geography atrophy (GA) with intravitreal pegcetacoplan and to identify utility-measurement surrogates.

DESIGN: Cost analysis based on data from a published study.

SUBJECTS: None; based on data from published sham control compared with 2 treatment groups in the index study.

METHODS: Costs were based on 2022 Medicare reimbursement data. Specific outcomes were extrapolated from the DERBY and OAKS trials. Assumptions were made for the lifetime analysis based on a theoretical logistic growth model of the atrophy.

OUTCOME MEASURES: Cost, cost utility, cost per quality-adjusted life-year, and cost per area of GA (in US$).

RESULTS: The costs to treat GA in every month (EM) and every-other-month (EOM) treatment groups over the 2 years as reported were $70 000 and $34 600, respectively. The costs per area of delaying GA for 2 years in all patients were $87 300/mm2 (EM) and $49 200/mm2 (EOM), and in initially extrafoveal patients, $53 900/mm2 (EM) and $32 100/mm2 (EOM). The costs per day of delaying GA for 2 years were $295 (EM) and $170 (EOM); the marginal cost (EM vs. EOM) per retinal pigment epithelium cell saved was $30. The modeled lifetime costs were $350 000 (EM) and $172 000 (EOM), or $309 000/mm2 (EM) and $180 000 (EOM) /mm2. The modeled time to 95\% atrophy at 13 years was delayed by 2.5 years (EM) and 2.1 years (EOM). The costs/quality-adjusted life-year gained based on modeled visual loss with 95\% atrophy were $706 000 (EM) and $397 000 (EOM).

CONCLUSION: Treatment of GA with intravitreal pegcetacoplan EOM was more cost effective than EM. Treatment of extrafoveal lesions yielded greater utility than the treatment of the entire group. As atrophy progression approaches an upper limit, the marginal cost/benefit ratios increase.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Aged, Atrophy, Cost-Effectiveness Analysis, Geographic Atrophy, Humans, Medicare, United States},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.08.003},
	author = {Patel, Nimesh A and Al-Khersan, Hasenin and Yannuzzi, Nicolas A and Lin, James and Smiddy, William E}
}
@article {1615209,
	title = {A Cost-Effectiveness Analysis of Intravitreal Aflibercept for the Prevention of Progressive Diabetic Retinopathy},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {3},
	year = {2022},
	month = {2022 Mar},
	pages = {213-218},
	abstract = {PURPOSE: To calculate costs required to prevent center-involved diabetic macular edema (CI-DME) or proliferative diabetic retinopathy (PDR), and to improve the diabetic retinopathy severity score (DRSS) with intravitreal anti-VEGF injections, as reported for aflibercept in 2 randomized control trials. DESIGN: Cost-effectiveness analysis modeling based on published data. SUBJECTS: None. METHODS: Results from PANORAMA and the Diabetic Retinopathy Clinical Research Network Protocol W were analyzed. Parameters collected included DRSS, risk reduction of PDR, risk reduction of CI-DME, and the number of treatments required. Costs were modeled based on 2020 Medicare reimbursement data practice settings of hospital-based facility and nonfacility. MAIN OUTCOME MEASURES: Cost to prevent cases of PDR and CI-DME and to improve DRSS stage. RESULTS: Over 2 years in Protocol W, the cost required to prevent 1 case of PDR was $83 000 ($72 400) in the facility (nonfacility) setting; in PANORAMA, the corresponding 2-year costs were $89 400 ($75 000) for the 2-mg aflibercept every 16 weeks (2Q16) arm, and $91 200 ($89 900) for the 2-mg aflibercept every 8 weeks as needed (2Q8PRN) arm. To prevent 1 case of CI-DME with vision loss in Protocol W, the cost was $154 000 ($133 000). For all CI-DME, with and without vision loss, in PANORAMA, the costs to prevent a case were $70 900 ($59 500) for the 2Q16 arm and $90 000 ($88 800) for the 2Q8PRN arm. In Protocol W, the overall accumulated total for cost/DRSS unit change at the 2-year point for facility (nonfacility) setting was $2700 ($2400)/DRSS. In the first year alone, it was $2100 ($1800)/DRSS and in the second year, it was $6100 ($5300)/DRSS. CONCLUSIONS: There is a considerable cost associated with the prevention of PDR and CI-DME with intravitreal aflibercept injections. A price per unit of change in DRSS is a new parameter that might serve as a benchmark in future utility analyses that could be used to bring the perspective to cost-utility considerations.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2021.09.005},
	author = {Patel, Nimesh A and Yannuzzi, Nicolas A and Lin, James and Smiddy, William E}
}
@article {1647891,
	title = {Practice Patterns and Outcomes of Intravitreal Anti-VEGF Injection for Retinopathy of Prematurity: An International Multicenter Study},
	journal = {Ophthalmology},
	volume = {129},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {1380-1388},
	abstract = {PURPOSE: To report practice patterns of intravitreal injections of anti-VEGF for retinopathy of prematurity (ROP) and outcomes data with a focus on retreatments and complications. DESIGN: Multicenter, international, retrospective, consecutive series. SUBJECTS: Patients with ROP treated with anti-VEGF injections from 2007 to\&nbsp;2021. METHODS: Twenfty-three sites (16 United States [US] and 7 non-US) participated. Data collected included demographics, birth characteristics, examination findings, and methods of injections. Comparisons between US and non-US sites were made. MAIN OUTCOME MEASURES: Primary outcomes included number and types of retreatments as well as complications. Secondary outcomes included specifics of the injection protocols, including types of medication, doses, distance from limbus, use of antibiotics, and quadrants where injections were delivered. RESULTS: A total of 1677 eyes of 918 patients (43\% female, 57\% male) were included. Mean gestational age was 25.7 weeks (range, 21.2-41.5 weeks), and mean birth weight was 787 g (range, 300-2700 g). Overall, a 30-gauge needle was most commonly used (51\%), and the quadrant injected was most frequently the inferior-temporal (51.3\%). The distance from the limbus ranged from 0.75 to 2 mm, with 1 mm being the most common (65\%). Bevacizumab was the most common anti-VEGF (71.4\%), with a dose of 0.625 mg in 64\% of cases. Overall, 604 (36\%) eyes required retreatment. Of those, 79.8\% were retreated with laser alone, 10.6\% with anti-VEGF injection alone, and 9.6\% with combined laser and injection. Complications after anti-VEGF injections occurred in 15 (0.9\%) eyes, and no cases of endophthalmitis were reported. Patients in the United States had lower birth weights and gestational ages (665.6 g and 24.5 weeks, respectively) compared with non-US patients (912.7 g and 26.9 weeks, respectively) (P \&lt; 0.0001). Retreatment with reinjection and laser was significantly more common in the US compared with the non-US group (8.5\% vs. 4.7\% [P\&nbsp;= 0.0016] and 55\% vs. 7.2\% [P \&lt; 0.001], respectively). There was no difference in the incidence of complications between the 2 geographic subgroups. CONCLUSIONS: Anti-VEGF injections for ROP were safe and well tolerated despite a variance in practice patterns. Infants with ROP receiving injections in the US tended to be younger and smaller, and they were treated earlier with more retreatments than non-US neonates with ROP.},
	keywords = {Angiogenesis Inhibitors, Antibodies, Monoclonal, Bevacizumab, Birth Weight, Female, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Newborn, Diseases, Intravitreal Injections, Male, Retinopathy of Prematurity, Retrospective Studies, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.07.009},
	author = {Patel, Nimesh A and Acaba-Berrocal, Luis A and Hoyek, Sandra and Fan, Kenneth C and Martinez-Castellanos, Maria Ana and Baumal, Caroline R and Harper, C Armitage and Berrocal, Audina M and Retinopathy of Prematurity Injection Consortium}
}
@article {1688286,
	title = {Design of medical tympanostomy conduits with selective fluid transport properties},
	journal = {Sci Transl Med},
	volume = {15},
	number = {690},
	year = {2023},
	month = {2023 Apr 05},
	pages = {eadd9779},
	abstract = {Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary-length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.},
	keywords = {Anti-Bacterial Agents, Ear, Middle, Humans, Middle Ear Ventilation, Otitis Media with Effusion, Prostheses and Implants},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.add9779},
	author = {Patel, Haritosh and Pavlichenko, Ida and Grinthal, Alison and Zhang, Cathy T and Alvarenga, Jack and Kreder, Michael J and Weaver, James C and Ji, Qin and Ling, Christopher W F and Choy, Joseph and Zihan Li and Black, Nicole L and Bispo, Paulo J M and Jennifer A. Lewis and Kozin, Elliott D and Aizenberg, Joanna and Remenschneider, Aaron K}
}
@article {1773421,
	title = {Reply},
	journal = {Ophthalmol Retina},
	volume = {8},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {e4},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.09.020},
	author = {Patel, Nimesh A and Al-Khersan, Hasenin and Yannuzzi, Nicolas A and Lin, James and Smiddy, William E}
}
@article {1658685,
	title = {Aflibercept Monotherapy versus Bevacizumab-First for Diabetic Macular Edema: A Cost Analysis Based on Diabetic Retinopathy Clinical Research Network Protocol AC Results},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {413-419},
	abstract = {PURPOSE: To calculate the costs of treatment for diabetic macular edema with bevacizumab-first (step therapy) compared with aflibercept monotherapy. DESIGN: Cost analysis of the treatment arms based on a published study. SUBJECTS: None. METHODS: Published results from the Diabetic Retinopathy Clinical Research Network protocol AC were used to assess costs. Data incorporated in the usage and outcome model included the frequency of injections, medication type, visits, and imaging. Costs were modeled based on the 2022 Medicare reimbursement data for both facility (hospital-based) and nonfacility settings in Miami. Outcomes were similar in protocol AC so were not differentially studied. Results were extrapolated so as to estimate lifetime (17 years for the age of the cohort). MAIN OUTCOME MEASURES: Cost of treatment options. RESULTS: Over the 2 years reported in the protocol AC, the cost required to treat in the facility (nonfacility setting) was $42 000 ($32 000) in the aflibercept monotherapy group and $29 000 ($22 000) in the bevacizumab-first group. Extrapolated modeled lifetime costs were $158 000 ($136 000) and $125 000 ($103 000), respectively. The total cost with bevacizumab-first was 33\% lower at year 2 and 21\% lower at year 17 compared with aflibercept monotherapy. Savings per year for the 2 years results were $6500 ($5000) in the facility (nonfacility) setting. For the extrapolated 17 years model, annual savings were $1900 ($1900) in the facility (nonfacility) setting. The professional fees accounted for a minority of overall costs; in contrast, medication costs accounted for 82\% of the total costs for the aflibercept monotherapy and 73\% in the bevacizumab-first group at 2 years. Our model predicted an additional 15\% lifetime cumulative savings if patients still not meeting the threshold criteria after switching to aflibercept were placed back on bevacizumab, and a similar degree of improvement if those on not meeting threshold criteria on aflibercept monotherapy were switched to bevacizumab. CONCLUSIONS: Medication is the dominant driver of the total expenses associated with the treatment of diabetic macular edema. Although cost savings are realized with bevacizumab-first step therapy, the magnitude was not as much as might be intuited, probably because of the high (70\%) incidence of patients switching to aflibercept within protocol AC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Aged, Angiogenesis Inhibitors, Bevacizumab, Costs and Cost Analysis, Diabetes Mellitus, Diabetic Retinopathy, Humans, Intravitreal Injections, Macular Edema, Medicare, Ranibizumab, United States},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.11.010},
	author = {Patel, Nimesh A and Al-Khersan, Hasenin and Yannuzzi, Nicolas A and Lin, James and Smiddy, William E}
}
@article {1363182,
	title = {Gaze-evoked amaurosis from orbital breast carcinoma metastasis},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {4},
	year = {2013},
	month = {2013 Jul-Aug},
	pages = {e98-e101},
	abstract = {Gaze-evoked amaurosis (GEA) is a transient monocular vision loss provoked by eccentric gaze. Gaze-evoked amaurosis has been associated with a variety of orbital lesions, most commonly optic nerve sheath meningiomas and cavernous hemangiomas. The authors describe the first report in the literature of GEA as the presenting symptom of an orbital metastasis. The patient was a 47-year-old woman with a history of breast cancer with no known history of metastasis or active disease who presented with several weeks of vision loss in the OD upon rightward gaze. She was found to have enophthalmos and optic disc edema of the OD. Imaging revealed an intraorbital lesion, and a biopsy was consistent with a scirrhous metastasis of her breast carcinoma. This case highlights the importance of considering orbital metastases among the differential for gaze-evoked amaurosis.},
	keywords = {Blindness, Breast Neoplasms, Carcinoma, Female, Humans, Middle Aged, Orbital Neoplasms},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31827defc7},
	author = {Patel, Mrinali M and Lefebvre, Daniel R and Lee, N Grace and Brachtel, Elena and Rizzo, Joseph and Freitag, Suzanne K}
}
@article {1632285,
	title = {Modernizing the American Journal of Ophthalmology: Social Media, Podcasts, and Digital Illustrations},
	journal = {Am J Ophthalmol},
	volume = {239},
	year = {2022},
	month = {2022 07},
	pages = {ix-x},
	keywords = {Humans, Ophthalmology, Social Media, United States},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.02.005},
	author = {Patel, Nimesh A and Powers, Sarah L Duncan and Parrish, Richard K}
}
@article {468996,
	title = {Orbital Branch of the Infraorbital Artery: Further Characterization of an Important Surgical Landmark.},
	journal = {Orbit},
	volume = {34},
	number = {4},
	year = {2015},
	month = {2015 Aug},
	pages = {212-5},
	abstract = {The orbital branch of the infraorbital artery, a key vascular structure that is not universally noted in orbital textbooks and atlases, is clinically significant, since injury to it can result in perioperative hemorrhage. We conducted a cadaver dissection to document its presence, measure its location, and evaluate it histopathologically. It was present in 8 of 9 orbits and was a mean distance of 16.6 mm (range 10-23) from the inferior orbital rim. In half of the specimens, there were 2 separate structures seen. Histopathology confirmed these structures to be neurovascular bundles.},
	issn = {1744-5108},
	doi = {10.3109/01676830.2015.1029137},
	author = {Patel, Avni V and Rashid, Alia and Jakobiec, Frederick A and Lefebvre, Daniel R and Yoon, Michael K}
}
@article {669311,
	title = {Risk of Retinal Neovascularization in Cases of Uveitis.},
	journal = {Ophthalmology},
	volume = {123},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {646-54},
	abstract = {PURPOSE: To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with uveitis at 4 US academic ocular inflammation subspecialty practices. METHODS: Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate. MAIN OUTCOME MEASURES: Prevalence and incidence of NV. RESULTS: Among uveitic eyes of 8931 patients presenting for initial evaluation, 106 of 13 810 eyes had NV (prevalence\&nbsp;= 0.77\%, 95\% confidence interval [CI], 0.60-0.90). Eighty-eight more eyes developed NV over 26\&nbsp;465 eye-years (incidence, 0.33\%/eye-year; 95\% CI, 0.27-0.41). Factors associated with incident NV include age \&lt;35 years compared with \&gt;35 years (adjusted hazard ratio [aHR], 2.4; 95\% CI, 1.5-3.9), current cigarette smoking (aHR, 1.9; 95\% CI, 1.1-3.4), and systemic lupus erythematosus (aHR, 3.5, 95\% CI, 1.1-11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared with patients diagnosed \&gt;5 years ago, aHR, 2.4 [95\% CI, 1.1-5.0] and aHR, 2.6 [95\% CI, 1.2-6.0] for diagnosis within \&lt;1 year vs. 1-5 years, respectively). Compared with anterior uveitis, intermediate uveitis (aHR, 3.1; 95\% CI, 1.5-6.6), posterior uveitis (aHR, 5.2; 95\% CI, 2.5-11), and panuveitis (aHR, 4.3; 95\% CI, 2.0-9.3) were associated with a similar degree of increased NV incidence. Active (aHR, 2.1, 95\% CI, 1.2-3.7) and slightly active (aHR, 2.4, 95\% CI, 1.3-4.4) inflammation were associated with an increased incidence of NV compared with inactive inflammation. Neovascularization incidence also was increased with retinal vascular occlusions (aHR, 10, 95\% CI, 3.0-33), retinal vascular sheathing (aHR, 2.6, 95\% CI, 1.4-4.9), and exudative retinal detachment (aHR, 4.1, 95\% CI, 1.3-13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR, 2.3, 95\% CI, 1.1-4.9), and systemic hypertension (aHR 1.5, 95\% CI, 0.89-2.4) was associated with nonsignificantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus. CONCLUSIONS: Retinal NV is a rare complication of uveitis, which occurs more frequently in younger patients, smokers, and those with intermediate/posterior/panuveitis, systemic vasculopathy, retinal vascular disease, or active inflammation. Inflammation and retinal NV likely are linked; additional studies are needed to further elucidate this connection.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.10.056},
	author = {Patel, Apurva K and Newcomb, Craig W and Liesegang, Teresa L and Pujari, Siddharth S and Suhler, Eric B and Thorne, Jennifer E and Foster, C Stephen and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Sen, H Nida and Artornsombudh, Pichaporn and Kothari, Srishti and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases Research Group}
}
@article {1677631,
	title = {Retinopathy of Prematurity Outcomes of Neonates Meeting Only a Single Screening Criterion: Proposal of the TWO-ROP Algorithm},
	journal = {Am J Ophthalmol},
	volume = {252},
	year = {2023},
	month = {2023 Aug},
	pages = {147-152},
	abstract = {PURPOSE: To assess the rates of retinopathy of prematurity (ROP) and treatment-warranted ROP in a modern set of patients meeting 0 or 1 of the current ROP screening criteria. DESIGN: Retrospective cohort study. METHODS: Single-center study of 9350 infants screened for ROP from 2009 to 2019. Rates of ROP and treatment-warranted ROP were evaluated in group 1 (birth weight [BW] \&lt;1500 g and gestational age [GA] >=30 weeks), group 2 (BW >=1500 g and GA \&lt;30 weeks), and group 3 (BW >=1500 g and GA >=30 weeks). RESULTS: Of 7520 patients with reported BW and GA, 1612 (21.4\%) patients met the inclusion criteria. The number of patients in groups 1, 2, and 3 was 466 (6.19\%), 23 (0.31\%), and 1123 (14.93\%), respectively. The number of patients diagnosed with ROP was 20 (4.29\%) in group 1, 1 (4.35\%) in group 2, and 12 (1.07\%) in group 3 (P \&lt; .001). The mean interval between birth and ROP diagnosis was 36.25 days (range 12-75 days) in group 1, 47 days in group 2, and 23.33 days (range 10-39 days) in group 3 (P\&nbsp;=\&nbsp;.05). No cases of stage 3, zone 1, or plus disease were recorded. No patients met the treatment criteria. CONCLUSIONS: Patients meeting 1 screening criterion had a low rate of ROP (\&lt;5\%), with no stage 3, zone 1, or plus disease. No patients required treatment. We propose a possible algorithm (TWO-ROP) in appropriate neonatal intensive care units, with an amendment in screening protocol for this low-risk population to include only an outpatient screening examination within 1 week of discharge, or at 40 weeks if inpatient, to decrease the inpatient ROP screening burden while maintaining safety. Further external validation of this protocol would be required.},
	keywords = {Birth Weight, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Premature, Infant, Very Low Birth Weight, Neonatal Screening, Retinopathy of Prematurity, Retrospective Studies, Risk Factors},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.03.007},
	author = {Patel, Nimesh A and Hoyek, Sandra and Al-Khersan, Hasenin and Fan, Kenneth C and Yannuzzi, Nicolas A and Davila, Jose and Berrocal, Audina M}
}
@article {1789031,
	title = {Transcriptional Comparison of Human and Murine Retinal Neovascularization},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {15},
	year = {2023},
	month = {2023 Dec 01},
	pages = {46},
	abstract = {PURPOSE: Retinal neovascularization (RNV) is the leading cause of vision loss in diseases like proliferative diabetic retinopathy (PDR). A significant failure rate of current treatments indicates the need for novel treatment targets. Animal models are crucial in this process, but current diabetic retinopathy models do not develop RNV. Although the nondiabetic oxygen-induced retinopathy (OIR) mouse model is used to study RNV development, it is largely unknown how closely it resembles human PDR. METHODS: We therefore performed RNA sequencing on murine (C57BL/6J) OIR retinas (n = 14) and human PDR RNV membranes (n = 7) extracted during vitrectomy, each with reference to control tissue (n=13/10). Differentially expressed genes (DEG) and associated biological processes were analyzed and compared between human and murine RNV to assess molecular overlap and identify phylogenetically conserved factors. RESULTS: In total, 213 murine- and 1223 human-specific factors were upregulated with a small overlap of 94 DEG (7\% of human DEG), although similar biological processes such as angiogenesis, regulation of immune response, and extracellular matrix organization were activated in both species. Phylogenetically conserved mediators included ANGPT2, S100A8, MCAM, EDNRA, and CCR7. CONCLUSIONS: Even though few individual genes were upregulated simultaneously in both species, similar biological processes appeared to be activated. These findings demonstrate the potential and limitations of the OIR model to study human PDR and identify phylogenetically conserved potential treatment targets for PDR.},
	keywords = {Animals, Diabetic Retinopathy, Disease Models, Animal, Humans, Mice, Mice, Inbred C57BL, Oxygen, Retinal Diseases, Retinal Neovascularization},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.15.46},
	author = {Pauleikhoff, Laurenz and Boneva, Stefaniya and Boeck, Myriam and Schlecht, Anja and Schlunck, G{\"u}nther and Agostini, Hansj{\"u}rgen and Lange, Clemens and Wolf, Julian}
}
@article {1632304,
	title = {Large Subconjunctival Mass in a Patient With a History of Multiple Previous Ocular Surgeries},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {5},
	year = {2022},
	month = {2022 May 01},
	pages = {534-535},
	keywords = {Conjunctiva, Conjunctival Diseases, Humans, Ophthalmologic Surgical Procedures, Ophthalmology},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.5262},
	author = {Pavlenko, Dmytro and Birnbaum, Faith A and Chen, Teresa C}
}
@article {1677646,
	title = {A comparative assessment of subjective experience in simulator and on-road driving under normal and time pressure driving conditions},
	journal = {Int J Inj Contr Saf Promot},
	volume = {30},
	number = {1},
	year = {2023},
	month = {2023 Mar},
	pages = {116-131},
	abstract = {This study conducts a comparative assessment of subjective experience of real-world and simulated world driving for investigating factors leading to simulator sickness. Thirty professional car drivers drove a fixed-base driving simulator in real and simulated worlds under No Time Pressure (NTP) and Time Pressure (TP) driving conditions. Drivers rated their perceptions based on real-world driving and simulator driving experiences after each driving session with respect to three factors: simulator sickness, mental workload, and sense of presence. The structural equation model results revealed that drivers experienced high mental workload due to TP driving conditions (factor loading = 0.90) and repeated exposure to simulated world (factor loading = 0.20) which induced simulator sickness (factor loading = 0.41) and resulted in low sense of presence (factor loading = -0.18). Thus, it can be concluded that lack of experience with virtual reality induced high simulator sickness, increased mental workload, and low sense of presence.},
	keywords = {Automobile Driving, Computer Simulation, Humans, Workload},
	issn = {1745-7319},
	doi = {10.1080/17457300.2022.2114091},
	author = {Pawar, Nishant Mukund and Yadav, Ankit Kumar and Velaga, Nagendra R}
}
@article {541241,
	title = {Photoreceptor rescue by an abbreviated human RPGR gene in a murine model of X-linked retinitis pigmentosa.},
	journal = {Gene Ther},
	volume = {23},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {196-204},
	abstract = {The X-linked RP3 gene codes for the ciliary protein RPGR and accounts for over 10\% of inherited retinal degenerations. The critical RPGR-ORF15 splice variant contains a highly repetitive purine-rich linker region that renders it unstable and difficult to adapt for gene therapy. To test the hypothesis that the precise length of the linker region is not critical for function, we evaluated whether adeno-associated virus-mediated replacement gene therapy with a human ORF15 variant containing in-frame shortening of the linker region could reconstitute RPGR function in vivo. We delivered human RPGR-ORF15 replacement genes with deletion of most (314 codons, {\textquoteright}short form{\textquoteright}) or 1/3 (126 codons, {\textquoteright}long form{\textquoteright}) of the linker region to Rpgr null mice. Human RPGR-ORF15 expression was detected post treatment with both forms of ORF15 transgenes. However, only the long form correctly localized to the connecting cilia and led to significant functional and morphological rescue of rods and cones. Thus the highly repetitive region of RPGR is functionally important but that moderate shortening of its length, which confers the advantage of added stability, preserves its function. These findings provide a theoretical basis for optimizing replacement gene design in clinical trials for X-linked RP3.},
	issn = {1476-5462},
	doi = {10.1038/gt.2015.93},
	author = {Pawlyk, B S and Bulgakov, O V and Sun, X and Adamian, M and Shu, X and Smith, A J and Berson, E L and Ali, R R and Khani, S and Wright, A F and Sandberg, M A and Li, T}
}
@article {836936,
	title = {American Society of Anesthesiologists classification in cataract surgery: Results from the Ophthalmic Surgery Outcomes Data Project.},
	journal = {J Cataract Refract Surg},
	volume = {42},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {972-82},
	abstract = {PURPOSE: To explore the association of American Society of Anesthesiologists (ASA) classification with cataract surgery outcomes. SETTING: Five Veterans Affairs Medical Centers, United States. DESIGN: Retrospective observational cohort study. METHODS: The study analyzed the outcomes of cataract surgery cases. Corrected distance visual acuity (CDVA), unanticipated events, and vision-related quality of life (VRQL) were assessed using the National Eye Institute Visual Function Questionnaire (NEI-VFQ), comparing ASA classes I through IV. For some analyses, ASA classes I and II were designated as Group A and ASA classes III and IV were designated Group B. RESULTS: Of the 4923 cases, 875 (17.8\%) were in Group A, 4032 (81.9\%) were in Group B, and 16 (0.3\%) had missing data. The mean CDVA and mean composite NEI-VFQ score improved after cataract surgery in both groups (P\&nbsp;\&lt;\&nbsp;.0001); however, Group A had a better mean postoperative CDVA and postoperative VFQ composite scores than Group B (P\&nbsp;\&lt;\&nbsp;.0001, both outcomes). A higher ASA class was associated with an increased risk for 2 unanticipated events; that is, clinically significant macular edema (CSME) (Group A: 4 [0.47\%] versus Group B: 50 [1.28\%]; adjusted odds ratio [OR], 3.02; 95\% confidence interval [CI], 1.02-13.05; P\&nbsp;=\&nbsp;0.04) and readmission to the hospital within 30\&nbsp;days (2 [0.23\%] versus 56 [1.41\%]; OR, 8.26; 95\% CI, 1.71-148.62; P\&nbsp;=\&nbsp;.004) CONCLUSIONS: Among United States veterans, the ASA classification could be an important predictor of VRQL and visual outcomes. In this cohort, it was associated with an increased risk for 2\&nbsp;serious unanticipated events-CSME and readmission to the hospital-both costly, unwanted outcomes. FINANCIAL DISCLOSURE: Dr. Vollman is a consultant to Forsight Vision5. None of the authors has a financial or proprietary interest in any material or method mentioned.},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2016.04.032},
	author = {Payal, Abhishek R and Sola-Del Valle, David and Gonzalez-Gonzalez, Luis A and Cakiner-Egilmez, Tulay and Chomsky, Amy S and Vollman, David E and Baze, Elizabeth F and Lawrence, Mary and Daly, Mary K}
}
@article {314176,
	title = {Orbital fractures and ocular injury: is a postoperative ophthalmology examination necessary?},
	journal = {J Oral Maxillofac Surg},
	volume = {72},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {1533-40},
	abstract = {PURPOSE: To determine whether formal ophthalmology evaluation is necessary after operative repair of orbital fractures and the association of an ocular injury to the severity of facial injury. PATIENTS AND METHODS: This was a retrospective cohort study of patients with orbital fractures undergoing operative repair from 2005 to 2013. Subjects were included if they had undergone reconstruction of orbital floor fractures and had data from pre- and postoperative examinations by the oral and maxillofacial surgery and ophthalmology services available. The predictor variables included the service performing the ocular examination (oral and maxillofacial surgery or ophthalmology) and the number of fractures present. The outcome variables were the presence of pre- and postoperative ocular injuries. Logistic regression models were used to determine the relationship of the fracture number to ocular injury. RESULTS: A total of 28 subjects had undergone repair of orbital fractures with preoperative and postoperative examinations performed by both services. Preoperative ocular injuries were found in 17 of the 28 subjects. Those detected by oral and maxillofacial surgeons were limited to changes in visual acuity, pupillary response, and extraocular muscle dysfunction in 11 subjects. Two subjects had new postoperative ocular findings that were considered minor and did not alter management. An increasing number of facial fractures was associated with an increased risk of ocular trauma. Those with 3 or more fractures had an odds ratio of 14.625 (95\% confidence interval, 2.191 to 97.612, P = .006) for the presence of ocular injury. CONCLUSIONS: Operative repair of orbital fractures did not lead to new ocular injuries that would change the management. Thus, those without preoperative ocular injuries will not require a formal postoperative ophthalmology examination. However, the subjects with more fractures had an increased likelihood of ocular injuries.},
	keywords = {Adult, Eye Injuries, Female, Humans, Male, Middle Aged, Ophthalmology, Orbital Fractures, Physical Examination, Retrospective Studies},
	issn = {1531-5053},
	doi = {10.1016/j.joms.2014.03.008},
	author = {Peacock, Zachary S and Boulos, Toufic and Miller, John B and Gardiner, Matthew F and Chuang, Sung-Kiang and Troulis, Maria J}
}
@article {1424812,
	title = {Neuroprotective effects of PPARα in retinopathy of type 1 diabetes},
	journal = {PLoS One},
	volume = {14},
	number = {2},
	year = {2019},
	month = {2019},
	pages = {e0208399},
	abstract = {Diabetic retinopathy (DR) is a common neurovascular complication of type 1 diabetes. Current therapeutics target neovascularization characteristic of end-stage disease, but are associated with significant adverse effects. Targeting early events of DR such as neurodegeneration may lead to safer and more effective approaches to treatment. Two independent prospective clinical trials unexpectedly identified that the PPARα agonist fenofibrate had unprecedented therapeutic effects in DR, but gave little insight into the physiological and molecular mechanisms of action. The objective of the present study was to evaluate potential neuroprotective effects of PPARα in DR, and subsequently to identify the responsible mechanism of action. Here we reveal that activation of PPARα had a robust protective effect on retinal function as shown by Optokinetic tracking in a rat model of type 1 diabetes, and also decreased retinal cell death, as demonstrated by a DNA fragmentation ELISA. Further, PPARα ablation exacerbated diabetes-induced decline of visual function as demonstrated by ERG analysis. We further found that PPARα improved mitochondrial efficiency in DR, and decreased ROS production and cell death in cultured retinal neurons. Oxidative stress biomarkers were elevated in diabetic Pparα-/- mice, suggesting increased oxidative stress. Mitochondrially mediated apoptosis and oxidative stress secondary to mitochondrial dysfunction contribute to neurodegeneration in DR. Taken together, these findings identify a robust neuroprotective effect for PPARα in DR, which may be due to improved mitochondrial function and subsequent alleviation of energetic deficits, oxidative stress and mitochondrially mediated apoptosis.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0208399},
	author = {Pearsall, Elizabeth A and Cheng, Rui and Matsuzaki, Satoshi and Zhou, Kelu and Ding, Lexi and Ahn, Bumsoo and Kinter, Michael and Humphries, Kenneth M and Quiambao, Alexander B and Farjo, Rafal A and Ma, Jian-Xing}
}
@article {1333940,
	title = {Atypical Protein Kinase C: Breaking Down Barriers in Ocular Disease?},
	journal = {Am J Pathol},
	volume = {188},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {2142-2146},
	abstract = {This commentary highlights the article by Lin et\&nbsp;al that demonstrates the therapeutic potential of small-molecule atypical protein kinase C inhibitors in inflammatory ocular disease.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2018.07.006},
	author = {Pearsall, Elizabeth A and Connor, Kip M}
}
@article {1347438,
	title = {A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 7 to 12 Years},
	journal = {Ophthalmology},
	volume = {126},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {456-466},
	abstract = {PURPOSE: To compare visual acuity (VA) improvement in children aged 7 to 12 years with amblyopia treated with a binocular iPad game plus continued spectacle correction vs. continued spectacle correction alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: One hundred thirty-eight participants aged 7 to 12 years with amblyopia (33-72 letters, i.e., approximately 20/200 to 20/40) resulting from strabismus, anisometropia, or both. Participants were required to have at least 16 weeks of optical treatment in spectacles if needed or demonstrate no improvement in amblyopic-eye visual acuity (VA) for at least 8 weeks prior to enrollment. METHODS: Eligible participants (mean age 9.6 years, mean baseline VA of 59.6 letters, history of prior amblyopia treatment other than spectacles in 96\%) were randomly assigned to treatment for 8 weeks with the dichoptic binocular Dig Rush iPad game (prescribed for 1 hour per day 5 days per week) plus spectacle wear if needed (n\&nbsp;= 69) or continued spectacle correction alone if needed (n\&nbsp;= 69). MAIN OUTCOME MEASURES: Change in amblyopic-eye VA from baseline to 4 weeks, assessed by a masked examiner. RESULTS: At 4 weeks, mean amblyopic-eye VA letter score improved from baseline by 1.3 (2-sided 95\% confidence interval [CI]: 0.1-2.6; 0.026 logMAR) with binocular treatment and by 1.7 (2-sided 95\% CI: 0.4-3.0; 0.034 logMAR) with continued spectacle correction alone. After adjusment for baseline VA, the letter score difference between groups (binocular minus control) was -0.3 (95\% CI: -2.2 to 1.5, P\&nbsp;= 0.71, difference of -0.006 logMAR). No difference in letter scores was observed between groups when the analysis was repeated after 8 weeks of treatment (adjusted mean: -0.1, 98.3\% CI: -2.4 to 2.1). For the binocular group, adherence data from the iPad indicated that slightly more than half of the participants (58\% and 56\%) completed \&gt;75\% of prescribed treatment by the 4- and 8-week visits, respectively. CONCLUSIONS: In children aged 7 to 12 years who have received previous treatment for amblyopia other\&nbsp;than spectacles, there was no benefit to VA or stereoacuity from 4 or 8 weeks of treatment with the dichoptic binocular Dig Rush iPad game.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.10.032},
	author = {Pediatric Eye Disease Investigator Group and Holmes, Jonathan M and Manny, Ruth E and Lazar, Elizabeth L and Birch, Eileen E and Kelly, Krista R and Summers, Allison I and Martinson, Stacy R and Raghuram, Aparna and Colburn, Jeffrey D and Law, Christine and Marsh, Justin D and Bitner, Derek P and Kraker, Raymond T and Wallace, David K}
}
@article {509161,
	title = {Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis.},
	journal = {JAMA Neurol},
	volume = {72},
	number = {10},
	year = {2015},
	month = {2015 Oct 1},
	pages = {1170-4},
	abstract = {IMPORTANCE: The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. OBJECTIVES: To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3\%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. MAIN OUTCOMES AND MEASURES: Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. RESULTS: Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9\%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95\% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95\% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95\% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). CONCLUSIONS AND RELEVANCE: We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease.},
	issn = {2168-6157},
	doi = {10.1001/jamaneurol.2015.1444},
	author = {Peeler, Crandall E and De Lott, Lindsey B and Nagia, Lina and Lemos, Joao and Eggenberger, Eric R and Cornblath, Wayne T}
}
@article {1307456,
	title = {Congenital muscular dystrophy-dystroglycanopathy, type A, featuring bilateral retinal dysplasia and vertical angle kappa},
	journal = {J AAPOS},
	volume = {22},
	number = {3},
	year = {2018},
	month = {2018 Jun},
	pages = {242-244.e1},
	abstract = {Muscular dystrophy-dystroglycanopathy type A (MDDGA3), one of a group of diseases collectively known as congenital muscular dystrophies, is an alpha-dystroglycanopathy with characteristic brain and ocular abnormalities. We report the case of a 9-month-old boy with developmental delay whose family sought evaluation for esotropia. Subsequent examination, imaging, and testing revealed significant motor and cognitive delay, marked weakness with appendicular spasticity, and a diffuse brain malformation. In addition, the patient had poor visual acuity, nystagmus, optic nerve hypoplasia, bilateral retinal dysplasia and retinal dragging with a large vertical angle kappa, and an avascular peripheral retina. Genetic testing revealed two known heterozygous mutations in the POMGnT1 gene confirming MDDGA3. He was treated with botulinum toxin injections for his strabismus and continues to be followed, with planned laser ablation of the peripheral avascular retina.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2017.12.011},
	author = {Peiris, Timothy J and Indaram, Maanasa and Koo, Euna and Soul, Janet S and Hunter, David G}
}
@article {1323939,
	title = {CENTRAL SEROUS CHORIORETINOPATHY ASSOCIATED WITH STEROID ENEMA},
	journal = {Retin Cases Brief Rep},
	volume = {15},
	number = {1},
	year = {2021},
	month = {2021 Jan 01},
	pages = {15-17},
	abstract = {BACKGROUND/PURPOSE: To report a case of acute recurrent central serous chorioretinopathy that developed after a regimen of corticosteroid enemas and suppositories. METHODS: Observational case report. Fluorescein angiography and spectral domain optical coherence tomography. RESULTS: A 47-year-old male patient with ulcerative colitis managed through hydrocortisone enemas presented to clinic with a 1-day history of blurry vision of his left eye. Posterior segment examination revealed subretinal fluid in the superotemporal macula of the left eye extending centrally. After diagnosis of acute central serous chorioretinopathy, the patient was advised to taper steroid enemas and his visual symptoms and subretinal fluid resolved within the month. Seven years later, several months after using steroid suppositories for the first time since the original central serous chorioretinopathy episode, asymptomatic subretinal fluid accumulation with foveal sparing was found on routine ophthalmic examination. Three months later, most of this fluid had resolved with minimal residual subretinal fluid on clinical examination. CONCLUSION: Acute central serous chorioretinopathy may develop after corticosteroid enema or suppository use, a route of administration that has not been previously reported in association with the disease.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000745},
	author = {Peiris, Timothy J and El Rami, Hala E and Sun, Jennifer K}
}
@article {1732626,
	title = {The Invisibility of Scotomas I: The Carving Hypothesis},
	journal = {Optom Vis Sci},
	year = {2023},
	month = {2023 Jul 27},
	abstract = {SIGNIFICANCE: Veridical depictions of scene appearance with scotomas allow better understanding of the impact of field loss and may improve the development and implementation of rehabilitation. Explanation and depiction of the invisibility of scotoma may lead to patients{\textquoteright} understanding and thus better compliance with related treatments. PURPOSE: Simulations of perception with scotomas guide training, patient education, and rehabilitation research. Most simulations incorrectly depict scotomas as black patches, though the scotomas and the missing contents are usually invisible to patients. We present a novel approach to capture the reported appearance of scenes with scotomas. METHODS: We applied a content-aware image resizing algorithm to carve out the content elided under the scotoma. With video sequences we show how and why eye movements fail to increase the visibility of the carved scotomas. RESULTS: Numerous effects, reported by patients, emerge naturally from the scotoma carving. Carving-eliminated scotomas over natural images are barely visible, despite causing substantial distortions. Low resolution and contrast sensitivity at farther eccentricities and saccadic blur reduce the visibility of the distortions. In a walking scenario, static objects moving smoothly to the periphery disappear into, and then reemerge out of peripheral scotomas invisibly. CONCLUSIONS: Scotoma carving provides a viable hypothetical simulation of vision with scotomas, due to loss of neurons at the retinal ganglion cell level and higher. As a hypothesis, it generates predictions that lend themselves to future clinical testing. The different effects of scotomas due to loss of photoreceptors are left for follow-up work.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000002048},
	author = {Peli, Eli and Goldstein, Robert and Jung, Jae-Hyun}
}
@article {1538349,
	title = {2017 Charles F. Prentice Award Lecture: Peripheral Prisms for Visual Field Expansion: A Translational Journey},
	journal = {Optom Vis Sci},
	volume = {97},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {833-846},
	abstract = {On the occasion of being awarded the Prentice Medal, I was asked to summarize my translational journey. Here I describe the process of becoming a low-vision rehabilitation clinician and researcher, frustrated by the unavailability of effective treatments for some conditions. This led to decades of working to understand patients{\textquoteright} needs and the complexities and subtleties of their visual systems and conditions. It was followed by many iterations of developing vision aids and the techniques needed to objectively evaluate their benefit. I specifically address one path: the invention and development of peripheral prisms to expand the visual fields of patients with homonymous hemianopia, leading to our latest multiperiscopic prism (mirror-based design) with its clear 45{\textdegree} field-of-view image shift.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001590},
	author = {Peli, Eli}
}
@article {705111,
	title = {High-Power Prismatic Devices for Oblique Peripheral Prisms.},
	journal = {Optom Vis Sci},
	volume = {93},
	number = {5},
	year = {2016},
	month = {2016 May},
	pages = {521-33},
	abstract = {PURPOSE: Horizontal peripheral prisms for hemianopia provide field expansion above and below the horizontal meridian; however, there is a vertical gap leaving the central area (important for driving) without expansion. In the oblique design, tilting the bases of both prism segments toward the horizontal meridian moves the field expansion area vertically and centrally (closing the central gap) while the prisms remain in the peripheral location. However, tilting the prisms results also in a reduction of the lateral field expansion. Higher prism powers are needed to counter this effect. METHODS: We developed, implemented, and tested a series of designs aimed at increasing the prism power to reduce the central gap while maintaining wide lateral expansion. The designs included inserting the peripheral prisms into carrier lenses that included yoked prism in the opposite direction, combination of two Fresnel segments attached at the base and angled to each other (bi-part prisms), and creating Fresnel prism-like segments from nonparallel periscopic mirror pairs (reflective prisms). RESULTS: A modest increase in lateral power was achieved with yoked-prism carriers. Bi-part combination of 36Δ Fresnel segments provided high power with some reduction in image quality. Fresnel reflective prism segments have potential for high power with superior optical quality but may be limited in field extent or by interruptions of the expanded field. Extended apical scotomas, even with unilateral fitting, may limit the utility of very high power prisms. The high-power bi-part and reflective prisms enable a wider effective eye scanning range (more than 15 degrees) into the blind hemifield. CONCLUSIONS: Conventional prisms of powers higher than the available 57Δ are limited by the binocular impact of a wider apical scotoma and a reduced effective eye scanning range to the blind side. The various designs that we developed may overcome these limitations and find use in various other field expansion applications.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000000820},
	author = {Peli, Eli and Bowers, Alex R and Keeney, Karen and Jung, Jae-Hyun}
}
@article {1125376,
	title = {Multiplexing Prisms for Field Expansion},
	journal = {Optom Vis Sci},
	volume = {94},
	number = {8},
	year = {2017},
	month = {2017 Aug},
	pages = {817-829},
	abstract = {PURPOSE: Prisms used for field expansion are limited by the optical scotoma at a prism apex (apical scotoma). For a patient with two functioning eyes, fitting prisms unilaterally allows the other eye to compensate for the apical scotoma. A monocular patient{\textquoteright}s field loss cannot be expanded with a conventional or Fresnel prism because of the apical scotoma. A newly invented optical device, the multiplexing prism (MxP), was developed to overcome the apical scotoma limitation in monocular field expansion. METHODS: A Fresnel-prism-like device with alternating prism and flat elements superimposes shifted and see-through views, thus creating the (monocular) visual confusion required for field expansion and eliminating the apical scotoma. Several implementations are demonstrated and preliminarily evaluated for different monocular conditions with visual field loss. The field expansion of the MxP is compared with the effect of conventional prisms using calculated and measured perimetry. RESULTS: Field expansion without apical scotomas is shown to be effective for monocular patients with hemianopia or constricted peripheral field. The MxPs are shown to increase the nasal field for a patient with only one eye and for patients with bitemporal hemianopia. The MxPs placed at the far temporal field are shown to expand the normal visual field. The ability to control the contrast ratio between the two images is verified. CONCLUSIONS: A novel optical device is demonstrated to have the potential for field expansion technology in a variety of conditions. The devices may be inexpensive and can be constructed in a cosmetically acceptable format.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001102},
	author = {Peli, Eli and Jung, Jae-Hyun}
}
@article {1364524,
	title = {Idiopathic sclerosing orbital inflammation: a review of demographics, clinical presentation, imaging, pathology, treatment, and outcome},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {28},
	number = {1},
	year = {2012},
	month = {2012 Jan-Feb},
	pages = {79-83},
	abstract = {PURPOSE: To characterize clinical features, diagnostics studies, treatments, and outcomes of patients with histologically proven idiopathic sclerosing orbital inflammation (ISOI), to define optimal management for this recalcitrant disease, and to determine changes in characterization and management by comparing our results with the last significant literature review. METHODS: A search of the U.S. National Library of Medicine: National Institutes of Health{\textquoteright}s electronic database for cases and case series in the English literature of biopsy-proven ISOI published between March 1994 and September 2010 was conducted. A cross-literature review was performed to tabulate demographics, clinical findings, studies, treatments, and outcomes, which were compared with the ISOI data published by Rootman et al. (1994). RESULTS: Sixty-one cases, 71 eyes from 17 published reports, met inclusion criteria. No ethnic, sex, or comorbidity predilection was established. Patients typically presented in the fourth decade with proptosis (73\%), pain (49\%), and normal vision (44\%). Orbital imaging and histopathology were sparsely reported. Most common treatments involved systemic corticosteroids either alone (34\%) or combined with other modalities (51\%). CONCLUSIONS: Characteristics of the disease remain unchanged, and best management was not determined due to inconsistent reporting methods across the literature. Collaboration with established groups (i.e., European Group On Graves Orbitopathy (EUGOGO), International Thyroid Eye Disease Society (ITEDS)) or the formation of a new group of physicians and scientists to help develop a systematic approach for future reporting and evaluation was proposed.},
	keywords = {Adrenal Cortex Hormones, Combined Modality Therapy, Humans, Orbital Pseudotumor, Sclerosis},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e318238ecf7},
	author = {Pemberton, John D and Fay, Aaron}
}
@article {1154956,
	title = {Investigation of goldmann perimetry in evaluation of patients for upper eyelid blepharoplasty},
	journal = {Orbit},
	volume = {37},
	number = {1},
	year = {2018},
	month = {2018 Feb},
	pages = {48-52},
	abstract = {PURPOSE: To determine if preoperative Goldmann Visual Field (GVF) testing in patients with functional dermatochalasis accurately depicts the postoperative superior visual field (SVF) outcome. METHODS: A prospective cohort study was done to compare preoperative and postoperative GVF field tests in patients undergoing upper eyelid blepharoplasty for treatment of dermatochalasis. This study was conducted in accordance with the Declaration of Helsinki and approved by the University of Arkansas for Medical Sciences institutional review board. A preoperative GVF was obtained with the eyelids in the natural position (untaped) and then again with excess skin elevated (taped). One month post-blepharoplasty, another GVF was conducted with eyelids untaped. The pre- and post GVF tests were analyzed to determine if preoperative testing accurately predicts the SVF improvement post-blepharoplasty. RESULTS: Forty-six eyelids (23 patients) who underwent blepharoplasty for dermatochalasis were included. The preoperative testing underestimated 76\% (35/46) of cases by a mean of 61\%; and overestimated the final outcome in 24\% (11/46) of cases by mean of 23\%. Overall, the preoperative GVF testing underestimated the postoperative outcome by a mean of 35\%. CONCLUSION: Improvement of the SVF after a blepharoplasty is typically greater than the preoperative GVF testing predicts.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2017.1353115},
	author = {Pemberton, John D and Salter, Michael and Fay, Aaron and Thuro, Bradley and Spencer, Horace and Dajani, Omar}
}
@article {382426,
	title = {Naphazoline as a confounder in the diagnosis of carotid artery dissection.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {2},
	year = {2015},
	month = {2015 Mar-Apr},
	pages = {e33-5},
	abstract = {Diagnosing Horner Syndrome can be difficult in the setting of an incomplete triad. A 27-year-old man presented with unilateral eyelid droop and intermittent ipsilateral headaches, having already seen 7 physicians. Physical examination revealed unilateral ptosis but no pupillary miosis or facial anhidrosis. Inspection of his clinical photographs revealed elevation of the ipsilateral lower eyelid, suggesting sympathetic dysfunction. On further questioning, he admitted to naphazoline dependence. Reexamination after ceasing the naphazoline unveiled the anisocoria. Vascular imaging subsequently revealed carotid dissection, and the patient was started on anticoagulant and antiplatelet therapy. The ptosis persisted after conjunctival M{\"u}llerectomy. External levator resection was recommended, but patient declined. This case underscores the importance of clinical photography, meticulous medical record review, and complete medication history including over-the-counter preparations. Clinicians should meticulously inspect the lower eyelid in cases of atypical blepharoptosis and consider the effects of eye drops when inspecting pupils for miosis.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000059},
	author = {Pemberton, John D and MacIntosh, Peter W and Zeglam, Ahmaida and Fay, Aaron}
}
@article {313121,
	title = {Distribution of intraretinal exudates in diabetic macular edema during anti-vascular endothelial growth factor therapy observed by spectral domain optical coherence tomography and fundus photography.},
	journal = {Retina},
	volume = {34},
	number = {12},
	year = {2014},
	month = {2014 Dec},
	pages = {2407-15},
	abstract = {PURPOSE: To evaluate changes in the distribution and morphology of intraretinal microexudates and hard exudates (HEs) during intravitreal anti-vascular endothelial growth factor therapy in patients with persistent diabetic macular edema. METHODS: Twenty-four patients with persistent diabetic macular edema after photocoagulation were investigated in this prospective cohort study. Each eye was assigned to a loading dose of three anti-vascular endothelial growth factor treatments at monthly intervals. Additional single treatments were performed if diabetic macular edema persisted or recurred. Intraretinal exudates were analyzed over 6 months using spectral domain optical coherence tomography (SD-OCT) and fundus photography. RESULTS: Before treatment, microexudates were detected by SD-OCT as hyperreflective foci in 24 eyes, whereas HEs were seen in 22 eyes. During therapy, HE increased significantly in number and size. This was accompanied by accumulation of microexudates in the outer retina. Enlargement of hyperreflective structures in SD-OCT was accompanied by enlargement of HE at corresponding fundus locations. A rapid reduction in diabetic macular edema was seen in all patients, but to varying degrees. Patients with hemoglobin A1c levels \&lt;7\% and serum cholesterol \&lt;200 mg/dL formed fewer HEs and featured more edema reduction and visual acuity gain. CONCLUSION: Diabetic macular edema reduction during intravitreal anti-vascular endothelial growth factor therapy was accompanied by dynamic rearrangement of intraretinal exudates at corresponding locations in fundus photography and SD-OCT. Intraretinal aggregates of microexudates detectable as hyperreflective foci by SD-OCT may compose and precede HE before they become clinically visible.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000250},
	author = {Pemp, Berthold and De{\'a}k, G{\'a}bor and Prager, Sonja and Mitsch, Christoph and Lammer, Jan and Schmidinger, Gerald and Scholda, Christoph and Schmidt-Erfurth, Ursula and Bolz, Matthias and Diabetic Retinopathy Research Group Vienna}
}
@article {1658661,
	title = {Anti-angiogenic properties of microRNA-29a in preclinical ocular models},
	journal = {Proc Natl Acad Sci U S A},
	volume = {119},
	number = {45},
	year = {2022},
	month = {2022 Nov 08},
	pages = {e2204795119},
	abstract = {Abnormal neovascularization is an important cause of blindness in many ocular diseases, for which the etiology and pathogenic mechanisms remain incompletely understood. Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization. The miR-29a knockout (KO) mice displayed enhanced vessel pruning, resulting in a decreased vascularized area during retinal development. In contrast, miR-29a deletion in adult mice accelerated angiogenesis in preclinical disease models, including corneal neovascularization, oxygen-induced retinopathy, and choroidal neovascularization, while the administration of agomir-29a ameliorated pathological neovascularization. Furthermore, miR-29a exerted inhibitory effects on endothelial cell proliferation, migration, and tube formation capacities. RNA sequencing analysis of retinas from miR-29a KO mice and RNA interference experiments identified platelet-derived growth factor C and several extracellular matrix genes as downstream targets of miR-29a involved in regulating ocular angiogenesis. Our data suggest that miR-29a may be a promising clinical candidate for the treatment of neovascular diseases.},
	keywords = {Animals, Cell Proliferation, Choroidal Neovascularization, Eye, Mice, Mice, Knockout, MicroRNAs, RNA Interference},
	issn = {1091-6490},
	doi = {10.1073/pnas.2204795119},
	author = {Peng, De-Wei and Lan, Chun-Lin and Dong, Ling-Qin and Jiang, Meng-Xi and Xiao, Huan and D{\textquoteright}Amato, Robert J and Chi, Zai-Long}
}
@article {1424813,
	title = {Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina},
	journal = {Cell},
	volume = {176},
	number = {5},
	year = {2019},
	month = {2019 Feb 21},
	pages = {1222-1237.e22},
	abstract = {High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80\% of \&gt;60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of \&gt;190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2019.01.004},
	author = {Peng, Yi-Rong and Karthik Shekhar and Yan, Wenjun and Herrmann, Dustin and Sappington, Anna and Bryman, Gregory S and van Zyl, Tav{\'e} and Do, Michael Tri H and Regev, Aviv and Sanes, Joshua R}
}
@article {1559534,
	title = {LncRNA-MALAT1/miRNA-204-5p/Smad4 Axis Regulates Epithelial-Mesenchymal Transition, Proliferation and Migration of Lens Epithelial Cells},
	journal = {Curr Eye Res},
	volume = {46},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {1137-1147},
	abstract = {MATERIALS AND METHODS: LECs were cultured and induced with TGF-β2 (10\&nbsp;ng/mL). SiRNA against MALAT1 (Si-MALAT1) was transfected into LECs to knockdown the expression of MALAT1. To overexpress or knockdown miR-204-5p, miR-204-5p mimics (miR-204-5p mimics) and anti-miR-204-5p (miR-204-5p inhibitor) were transfected into LECs. We used RNA FISH to identify the location of MALAT1. RNA levels of MALAT1 and miR-204-5p were analyzed by RT-qPCR. Additionally, target protein levels of Smad4, epithelial differentiation and mesenchymal markers were analyzed with Western blot. We employed EdU Labeling to measured cell proliferation and performed Transwell Assay to analyze the cell migration. Dual-luciferase reporter assays in LECs were conducted to verify whether miRNA-204-5p was negatively regulated by MALAT1 and Smad4 was a direct target of miR-204-5p. RESULTS: The expression of MALAT1 was upregulated in PCO specimens. MALAT1 was overexpressed in TGF-β2 induced LECs, and the knockdown of MALAT1 could attenuate TGF-β2 induced EMT. Besides, the upregulation of MALAT1 was correlated with the downregulation of miR-204-5p and upregulation of Smad4. Importantly, MALAT1 was revealed to be located in the cytoplasm of LECs. Furthermore, luciferase reporter assays confirmed that MALAT1 could negatively regulate the expression of miR-204-5p and then regulate its direct target Smad4. Finally, the knockdown of MALAT1 could inhibit the EMT, proliferation, and migration of LECs; however, those can be reversed by anti-miR-204-5p. CONCLUSIONS: Our findings reveal that MALAT1 may regulate EMT, proliferation, and migration of LECs as a ceRNA by "sponging" miR-204-5p and targeting Smad4, and serve as a promising therapeutic target in preventing PCO.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2020.1857778},
	author = {Peng, Cheng and Wang, Yuchi and Ji, Liyang and Kuang, Liangju and Yu, Ziyan and Li, Hanrong and Zhang, Jinsong and Zhao, Jiangyue}
}
@article {1635630,
	title = {Bibliometric and visualized analysis of ocular drug delivery from 2001 to 2020},
	journal = {J Control Release},
	volume = {345},
	year = {2022},
	month = {2022 May},
	pages = {625-645},
	abstract = {OBJECTIVE: To perform a bibliometric analysis in the field of ocular drug delivery research to characterize the current international trends and to present visual representations of the past and emerging trends on ocular drug delivery research over the past decade. METHOD: In this cross-sectional study, a bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze evolution and theme trends on ocular drug delivery research from January 1, 2001, to December 31, 2020. A total of 4334 articles on ocular drug delivery were evaluated for specific characteristics, such as publication year, journals, authors, institutions, countries/regions, references, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed by VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. RESULTS: From 2001 to 2020, the annual global publications increased by 746.15\%, from 52 to 440. International Journal of Pharmaceutics published the most manuscripts (250 publications) and produced the highest citations (9509 citations), followed by Investigative Ophthalmology \&amp; Visual Science (202 publications) and Journal of Ocular Pharmacology and Therapeutics (136 publications). The United States (1289 publications, 31,512 citations), the University of Florida (82 publications, 2986 citations), and Chauhan, Anuj (52 publications, 2354 citations) were the most productive and impactful institution, country, and author respectively. The co-occurrence cluster analysis of the top 100 keywords form five clusters: (1) micro/nano ocular drug delivery systems; (2) the treatment of inflammation and posterior diseases; (3) macroscopic ocular drug delivery systems/devices; (4) the characteristics of drug delivery systems; (5) and the ocular drug delivery for glaucoma treatment. Diabetic macular edema, anti-VEGF, ranibizumab, bevacizumab, micelles and latanoprost, were the latest high-frequency keywords, indicating the emerging frontiers of ocular drug delivery. Further discussions into the subtopics were provided to assist researchers to determine the range of research topics and plan research direction. CONCLUSIONS: Over the last two decades there has been a progressive increase in the number of publications and citations on research related to ocular drug delivery across many countries, institutions, and authors. The present study sheds light on current trends, global collaboration patterns, basic knowledge, research hotspots, and emerging frontiers of ocular drug delivery. Novel solutions for ocular drug delivery and the treatment of inflammation and posterior diseases were the major themes over the last 20\&nbsp;years.},
	keywords = {Bibliometrics, Cross-Sectional Studies, Diabetic Retinopathy, Drug Delivery Systems, Humans, Inflammation, Macular Edema, United States},
	issn = {1873-4995},
	doi = {10.1016/j.jconrel.2022.03.031},
	author = {Peng, Cheng and Kuang, Liangju and Zhao, Jiangyue and Ross, Amy E and Wang, Zhongqing and Ciolino, Joseph B}
}
@article {669256,
	title = {Risk Factors for Proliferative Diabetic Retinopathy in African Americans with Type 2 Diabetes.},
	journal = {Ophthalmic Epidemiol},
	volume = {23},
	number = {2},
	year = {2016},
	month = {2016 Apr},
	pages = {88-93},
	abstract = {PURPOSE: To assess personal and demographic risk factors for proliferative diabetic retinopathy in African Americans with type 2 diabetes. METHODS: In this prospective, non-interventional, cross-sectional case-control study, 380 African Americans with type 2 diabetes were enrolled. Participants were recruited prospectively and had to have either: (1) absence of diabetic retinopathy after >=10 years of type 2 diabetes, or (2) presence of proliferative diabetic retinopathy when enrolled. Dilated, 7-field fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study scale. Covariates including hemoglobin A1C (HbA1C), blood pressure, height, weight and waist circumference were collected prospectively. Multivariate regression models adjusted for age, sex and site were constructed to assess associations between risk factors and proliferative diabetic retinopathy. RESULTS: Proliferative diabetic retinopathy was associated with longer duration of diabetes (odds ratio, OR, 1.62, p \&lt; 0.001), higher systolic blood pressure (OR 1.65, p \&lt; 0.001) and insulin use (OR 6.65, p \&lt; 0.001) in the multivariate regression analysis. HbA1C was associated with proliferative diabetic retinopathy in the univariate analysis (OR 1.31, p = 0.002) but was no longer significant in the multivariate analysis. CONCLUSIONS: In this case-control study of African Americans with type 2 diabetes, duration of diabetes, systolic hypertension and insulin use were strong risk factors for the development of proliferative diabetic retinopathy. Interestingly, HbA1C did not confer additional risk in this cohort.},
	issn = {1744-5086},
	doi = {10.3109/09286586.2015.1119287},
	author = {Penman, Alan and Hancock, Heather and Papavasileiou, Evangelia and James, Maurice and Idowu, Omolola and Riche, Daniel M and Fernandez, Marlene and Brauner, Stacey and Smith, Sataria O and Hoadley, Suzanne and Richardson, Cole and Vazquez, Vanessa and Chi, Cheryl and Andreoli, Christopher and Husain, Deeba and Chen, Ching J and Sobrin, Lucia}
}
@article {397846,
	title = {P-selectin Plasma Levels and Genetic Variant Associated With Diabetic Retinopathy in African Americans.},
	journal = {Am J Ophthalmol},
	volume = {159},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {1152-1160.e2},
	abstract = {PURPOSE: To report the prevalence and risk factors for retinopathy in African Americans with impaired fasting glucose (IFG) and type 2 diabetes in the Jackson Heart Study and to determine if P-selectin plasma levels are independently associated with retinopathy in this population. DESIGN: Prospective, cross-sectional observational study. METHODS: setting: Community-based epidemiologic study. STUDY POPULATION: Total of 629 patients with type 2 diabetes and 266 participants with impaired fasting glucose. OBSERVATION PROCEDURES: Bilateral, 7-field fundus photographs were scored by masked readers for diabetic retinopathy (DR) level. Covariate data including P-selectin plasma levels and genotypes were collected in a standardized fashion. MAIN OUTCOME MEASURES: Association between risk factors, including P-selectin plasma levels and genotypes, and retinopathy. RESULTS: The prevalences of any retinopathy among participants with IFG and type 2 diabetes were 9.4\% and 32.4\%, respectively. Among those with type 2 diabetes, in multivariate models adjusted for age, sex, and other traditional risk factors, higher P-selectin levels were associated with any DR (odds ratio\&nbsp;= 1.11, 95\% confidence interval\&nbsp;= 1.02-1.21, P\&nbsp;= .02) and proliferative DR (odds ratio\&nbsp;= 1.23, 95\% confidence interval\&nbsp;= 1.03-1.46, P\&nbsp;= .02). To further investigate the relationship between P-selectin and DR, we examined the association between P-selectin genotype and DR. Minor allele homozygotes for the variant rs6128 were less likely to develop DR (P after Bonferroni correction\&nbsp;= 0.03). CONCLUSIONS: Both serologic and genetic data show an association between P-selectin and DR in the Jackson Heart Study. If confirmed in other studies, this association may provide insight into the pathogenesis of retinopathy.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.03.008},
	author = {Penman, Alan and Hoadley, Suzanne and Wilson, James G and Taylor, Herman A and Chen, Ching J and Sobrin, Lucia}
}
@article {1538328,
	title = {Endoscopic endonasal resection of orbital schwannoma assisted with small-incision medial orbitotomy: case series and surgical technique},
	journal = {Orbit},
	volume = {40},
	number = {6},
	year = {2021},
	month = {2021 Dec},
	pages = {536-542},
	abstract = {PURPOSE: To describe a surgical approach for the resection of schwannomas occurring in the medial aspect of the orbit and to review a series of patients who underwent this novel technique. METHODS: This retrospective, non-comparative case series presents the surgical technique and outcomes of patients who underwent removal of a medial orbital schwannoma via an endoscopic endonasal approach combined with a small-incision medial orbitotomy by a team of two surgeons (BSB and SKF). Patient demographics, pre- and post-operative clinical examination findings, visual field testing, and radiographic studies were reviewed. Operative reports were reviewed for technical details and complications. RESULTS: The patients included a 12 year-old male, 73 year-old female and 8 year-old male. Indications for surgery included: decreased visual acuity, diplopia, proptosis and Humphrey visual field (HVF) deficit, in the presence of a medial orbital biopsy-proven schwannoma. The surgical approach in all three patients was primarily endoscopic endonasal. Additionally, two had transcaruncular orbitotomies and one had a small-incision medial lid crease orbitotomy to assist with lateral tumor dissection. Tumor resection was complete in one case and near-total in two cases. There were no intra-operative surgical complications. Average resected specimen volume was 3.41 cm3\&nbsp;{\textpm}\&nbsp;2.20. All patients had post-operative improvement in visual acuity (VA) and proptosis. Post-operative follow-up intervals were 27.5\&nbsp;months, 12.3\&nbsp;months and 3.5\&nbsp;months, respectively. CONCLUSION: Resection of orbital schwannomas using an endoscopic endonasal approach with small-incision medial transorbital assistance is a safe and effective option for a multidisciplinary surgical team.},
	keywords = {Aged, Child, Endoscopy, Exophthalmos, Female, Humans, Male, Neurilemmoma, Orbit, Retrospective Studies},
	issn = {1744-5108},
	doi = {10.1080/01676830.2020.1832123},
	author = {Pennington, Justin D and Bleier, Benjamin S and Freitag, Suzanne K}
}
@article {1466902,
	title = {Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface},
	journal = {Microorganisms},
	volume = {7},
	number = {9},
	year = {2019},
	month = {2019 Sep 13},
	abstract = {Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface.},
	issn = {2076-2607},
	doi = {10.3390/microorganisms7090351},
	author = {Pennington, Matthew R and Saha, Amrita and Painter, David F and Gavazzi, Christina and Ismail, Ashrafali M and Zhou, Xiaohong and Chodosh, James and Rajaiya, Jaya}
}
@article {280711,
	title = {Vascular Endothelial Growth Factor Acts Primarily via Platelet-Derived Growth Factor Receptor α to Promote Proliferative Vitreoretinopathy.},
	journal = {Am J Pathol},
	year = {2014},
	month = {2014 Sep 24},
	abstract = {Proliferative vitreoretinopathy (PVR) is a nonneovascular blinding disease and the leading cause for failure in surgical repair of rhegmatogenous retinal detachments. Once formed, PVR is difficult to treat. Hence, there is an acute interest in developing approaches to prevent PVR. Of the many growth factors and cytokines that accumulate in vitreous as PVR develops, neutralizing vascular endothelial growth factor (VEGF) A has recently been found to prevent PVR in at least one animal model. The goal of this study was to test if Food and Drug Administration-approved agents could protect the eye from PVR in multiple animal models and to further investigate the underlying mechanisms. Neutralizing VEGF with aflibercept (VEGF Trap-Eye) safely and effectively protected rabbits from PVR in multiple models of disease. Furthermore, aflibercept reduced the bioactivity of both experimental and clinical PVR vitreous. Finally, although VEGF could promote some PVR-associated cellular responses via VEGF receptors expressed on the retinal pigment epithelial cells that drive this disease, VEGF{\textquoteright}s major contribution to vitreal bioactivity occurred via platelet-derived growth factor receptor α. Thus, VEGF promotes PVR by a noncanonical ability to engage platelet-derived growth factor receptor α. These findings indicate that VEGF contributes to nonangiogenic diseases and that anti-VEGF-based therapies may be effective on a wider spectrum of diseases than previously appreciated.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2014.07.026},
	author = {Pennock, Steven and Haddock, Luis J and Mukai, Shizuo and Kazlauskas, Andrius}
}
@article {1363184,
	title = {Ranibizumab is a potential prophylaxis for proliferative vitreoretinopathy, a nonangiogenic blinding disease},
	journal = {Am J Pathol},
	volume = {182},
	number = {5},
	year = {2013},
	month = {2013 May},
	pages = {1659-70},
	abstract = {Proliferative vitreoretinopathy (PVR) exemplifies a disease that is difficult to predict, lacks effective treatment options, and substantially reduces the quality of life of an individual. Surgery to correct a rhegmatogenous retinal detachment fails primarily because of PVR. Likely mediators of PVR are growth factors in vitreous, which stimulate cells within and behind the retina as an inevitable consequence of a breached retina. Three classes of growth factors [vascular endothelial growth factor A (VEGF-A), platelet-derived growth factors (PDGFs), and non-PDGFs (growth factors outside of the PDGF family)] are relevant to PVR pathogenesis because they act on PDGF receptor α, which is required for experimental PVR and is associated with this disease in humans. We discovered that ranibizumab (a clinically approved agent that neutralizes VEGF-A) reduced the bioactivity of vitreous from patients and experimental animals with PVR, and protected rabbits from developing disease. The apparent mechanism of ranibizumab action involved derepressing PDGFs, which, at the concentrations present in PVR vitreous, inhibited non-PDGF-mediated activation of PDGF receptor α. These preclinical findings suggest that available approaches to neutralize VEGF-A are prophylactic for PVR, and that anti-VEGF-based therapies may be effective for managing more than angiogenesis- and edema-driven pathological conditions.},
	keywords = {Animals, Antibodies, Monoclonal, Humanized, Biomarkers, Blindness, Cell Line, Disease Susceptibility, Humans, Mice, Neutralization Tests, Platelet-Derived Growth Factor, Protein Multimerization, Rabbits, Ranibizumab, Receptor, Platelet-Derived Growth Factor alpha, Signal Transduction, Vascular Endothelial Growth Factor A, Vitreoretinopathy, Proliferative, Vitreous Body},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2013.01.052},
	author = {Pennock, Steven and David Kim and Mukai, Shizuo and Kuhnle, Matthew and Chun, Dal W and Matsubara, Joanne and Cui, Jing and Ma, Patrick and Maberley, David and Samad, Arif and Van Geest, Robert J and Oberstein, Sarit L and Schlingemann, Reinier O and Kazlauskas, Andrius}
}
@article {742301,
	title = {Vascular Endothelial Cell Growth Factor A Acts via Platelet-Derived Growth Factor Receptor α To Promote Viability of Cells Enduring Hypoxia.},
	journal = {Mol Cell Biol},
	volume = {36},
	number = {18},
	year = {2016},
	month = {2016 Sep 15},
	pages = {2314-27},
	abstract = {Vascular endothelial cell growth factor A (VEGF) is a biologically and therapeutically important growth factor because it promotes angiogenesis in response to hypoxia, which underlies a wide variety of both physiological and pathological settings. We report here that both VEGF receptor 2 (VEGFR2)-positive and -negative cells depended on VEGF to endure hypoxia. VEGF enhanced the viability of platelet-derived growth factor receptor α (PDGFRα)-positive and VEGFR2-negative cells by enabling indirect activation of PDGFRα, thereby reducing the level of p53. We conclude that the breadth of VEGF{\textquoteright}s influence extends beyond VEGFR-positive cells and propose a plausible mechanistic explanation of this phenomenon.},
	issn = {1098-5549},
	doi = {10.1128/MCB.01019-15},
	author = {Pennock, Steven and Kim, Leo A and Kazlauskas, Andrius}
}
@article {1364525,
	title = {Vascular endothelial growth factor A competitively inhibits platelet-derived growth factor (PDGF)-dependent activation of PDGF receptor and subsequent signaling events and cellular responses},
	journal = {Mol Cell Biol},
	volume = {32},
	number = {10},
	year = {2012},
	month = {2012 May},
	pages = {1955-66},
	abstract = {Certain platelet-derived growth factor (PDGF) isoforms are associated with proliferative vitreoretinopathy (PVR), a sight-threatening complication that develops in a subset of patients recovering from retinal reattachment surgery. Although these PDGF isoforms are abundant in the vitreous of patients and experimental animals with PVR, they make only a minor contribution to activating PDGF receptor α (PDGFRα) and driving experimental PVR. Rather, growth factors outside of the PDGF family are the primary (and indirect) agonists of PDGFRα. These observations beg the question of why vitreal PDGFs fail to activate PDGFRα. We report here that vitreous contains an inhibitor of PDGF-dependent activation of PDGFRα and that a major portion of this inhibitory activity is due to vascular endothelial cell growth factor A (VEGF-A). Furthermore, recombinant VEGF-A competitively blocks PDGF-dependent binding and activation of PDGFR, signaling events, and cellular responses. These findings unveil a previously unappreciated relationship between distant members of the PDGF/VEGF family that may contribute to pathogenesis of a blinding eye disease.},
	keywords = {Binding, Competitive, Cell Line, Humans, Platelet-Derived Growth Factor, Protein Binding, Receptors, Platelet-Derived Growth Factor, Recombinant Proteins, Retinal Pigment Epithelium, Signal Transduction, Vascular Endothelial Growth Factor A, Vitreoretinopathy, Proliferative},
	issn = {1098-5549},
	doi = {10.1128/MCB.06668-11},
	author = {Pennock, Steven and Kazlauskas, Andrius}
}
@article {1445329,
	title = {Optimized conditions and use of synthetic matrix for retinal differentiation from pluripotent cells},
	journal = {Tissue Eng Part C Methods},
	year = {2019},
	month = {2019 Jun 14},
	abstract = {PURPOSE: Since it was first introduced in 2011, three-dimensional "Sasai" method for retinal differentiation became a strategy of choice for retinal tissue and neuron production. It is based on the recapitulation of retinal development and requires several stages: aggregate formation, neuroectoderm induction, and eye field induction, followed by retinal maturation. In order to achieve the consistency of retinal differentiation needed for drug discovery and cell transplantation we have attempted to improve spheroid formation as well as approach xeno-free conditions. METHODS: In this study we compared the effect of cell culture plate shape and material, medium viscosity, lipid and bovine serum albumin concentrations on aggregate formation from mouse embryonic stem cells. We have also assessed the possibility of substituting Matrigel with the synthetic vitronectin-mimicking oligopeptide. RX-GFP mES cell line used for experiments. The dose-response of synthetic ECM has been assessed and quantified by live fluorescence microscopy, immunohistochemistry, flow cytometry and qPCR for early retinal development genes (Rx, Pax6, Lhx2, Sox2, Six6). RESULTS: The comparison of seeding conditions at 24hr. post seeding showed the dose-dependent effects of lipids (lipids concentration of 2\% resulted in 100\% efficiency of aggregate formation and significant increase in size to 532.8 {\textpm} 31.87um, p\&lt; 0.05); and viscosity (methylcellulose concentration of 0.06\% in OV medium showed 100\% efficiency and increase in aggregate size 532{\textpm}19.23 um, p\&lt;0.01). The addition of synthetic matrix resulted in retinal differentiation (34.47\% of RX as detected by flow cytometry compared to 33.8\%, observed with Matrigel). The early retinal genes expression at day 7 was confirmed by qPCR. CONCLUSIONS: We present the optimized conditions for 3D retinal differentiation including the option of xeno-free extracellular matrix. These defined medium conditions significantly decrease the variability within and between batches and allow substantial scale up of retinal tissue and cell production for drug discovery, disease modeling and transplantation purposes.},
	issn = {1937-3392},
	doi = {10.1089/ten.TEC.2019.0053},
	author = {Perepelkina, Tatiana and Kegeles, Evgenii and Baranov, Petr Y}
}
@article {1586170,
	title = {Artificial Intelligence (AI) Applications for Age-Related Macular Degeneration (AMD) and Other Retinal Dystrophies},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {304-309},
	abstract = {Artificial intelligence (AI), with its subdivisions (machine and deep learning), is a new branch of computer science that has shown impressive results across a variety of domains. The applications of AI to medicine and biology are being widely investigated. Medical specialties that rely heavily on images, including radiology, dermatology, oncology and ophthalmology, were the first to explore AI approaches in analysis and diagnosis. Applications of AI in ophthalmology have concentrated on diseases with high prevalence, such as diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration (AMD), and glaucoma. Here we provide an overview of AI applications for diagnosis, classification, and clinical management of AMD and other macular dystrophies.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1896756},
	author = {Perepelkina, Tatiana and Fulton, Anne B}
}
@article {1483610,
	title = {Enhancer transcription identifies -regulatory elements for photoreceptor cell types},
	journal = {Development},
	volume = {147},
	number = {3},
	year = {2020},
	month = {2020 Feb 05},
	abstract = {Identification of cell type-specific regulatory elements (CREs) is crucial for understanding development and disease, although identification of functional regulatory elements remains challenging. We hypothesized that context-specific CREs could be identified by context-specific non-coding RNA (ncRNA) profiling, based on the observation that active CREs produce ncRNAs. We applied ncRNA profiling to identify rod and cone photoreceptor CREs from wild-type and mutant mouse retinas, defined by presence or absence, respectively, of the rod-specific transcription factor (TF) -dependent ncRNA expression strongly correlated with epigenetic profiles of rod and cone photoreceptors, identified thousands of candidate rod- and cone-specific CREs, and identified motifs for rod- and cone-specific TFs. Colocalization of NRL and the retinal TF CRX correlated with rod-specific ncRNA expression, whereas CRX alone favored cone-specific ncRNA expression, providing quantitative evidence that heterotypic TF interactions distinguish cell type-specific CRE activity. We validated the activity of novel -dependent ncRNA-defined CREs in developing cones. This work supports differential ncRNA profiling as a platform for the identification of cell type-specific CREs and the discovery of molecular mechanisms underlying TF-dependent CRE activity.},
	issn = {1477-9129},
	doi = {10.1242/dev.184432},
	author = {Perez-Cervantes, Carlos and Smith, Linsin A and Nadadur, Rangarajan D and Hughes, Andrew E O and Wang, Sui and Corbo, Joseph C and Cepko, Constance and Lonfat, Nicolas and Moskowitz, Ivan P}
}
@article {1295875,
	title = {Solving the Hydroxychloroquine Dosing Dilemma With a Smartphone App},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {2},
	year = {2018},
	month = {2018 Feb 01},
	pages = {218-219},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.6076},
	author = {Perlman, Elliot M and Greenberg, Paul B and Browning, David and Friday, Robert P and Miller, Joan W}
}
@article {1364526,
	title = {The evaluation of patients with traumatic cataracts by ultrasound technologies},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {121-4},
	abstract = {Surgery for traumatic cataracts is a potentially complex procedure. Clinically, traumatic cataracts may be difficult to thoroughly assess due to the presence of other significant ocular damage including corneal scars, posterior synechiae, and vitreous hemorrhage. Frequently, surgery involves surprises regarding the integrity of the posterior capsule and zonular structure. Careful ophthalmic imaging using ultrasound technologies may result in finer pre-operative detail regarding lens support structures, and may therefore give the surgeon the advantage when planning surgery. Imaging techniques most applicable to pre-operative evaluation include B scan ultrasound, 20MHz ultrasound, and ultrasound biomicroscopy. Important modifications to technique that can be made depending on the integrity of lens support structures include adjustment of wound location, adjustment in the technique for cataract removal, and possible use of a capsular tension ring.},
	keywords = {Cataract, Eye Injuries, Humans, Lens, Crystalline, Microscopy, Acoustic},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.712733},
	author = {Perry, Lynn J Poole}
}
@article {1364527,
	title = {Giant dacryocystomucopyocele in an adult: a review of lacrimal sac enlargements with clinical and histopathologic differential diagnoses},
	journal = {Surv Ophthalmol},
	volume = {57},
	number = {5},
	year = {2012},
	month = {2012 Sep},
	pages = {474-85},
	abstract = {Dacryocystocele is an umbrella term that refers to any diffuse, centrifugal enlargement of the lacrimal sac that results from combined proximal and distal obstructions in the tear drainage system. In adults, the presence of mucus in the cyst{\textquoteright}s contents leads to the modified term of dacryocystomucocele. If infection supervenes, which almost always occurs in protracted cases and adds the clinical dimension of a dacryocystitis, then a dacryocystomucopyocele is created. Dacryocystocele and its congeners are much rarer in adults than in children. We describe a 95-year-old woman with an acquired, enormous dacryocystomucopyocele, larger than any previously reported, that developed over 25 years and produced globe displacement with an associated conspicuous enlargement of the nasolacrimal duct. The aspirated sac fluid was mucopurulent and harbored low-virulence bacterial organisms of the Prevotella and Petosteptococcus species. In infants, dacryocystoceles are transitory as the result of spontaneously reversible factors. In adults, secondary proximal irreversible fibrotic strictures or bony changes around the nasolacrimal duct typically arise from chronic inflammation or low grade infection. Other possible causations of duct obstruction, in addition to florid mucosal edema, include encroachment on the duct by enlarged contiguous ethmoid air cells; a sinus mucocele or sinusitis; idiopathic, post-traumatic or dysplastic bony remodeling of the wall of the duct; and a neoplasm-all of which require some form of surgical intervention, typically dacryocystorhinostomy. The differential diagnosis of medial canthal swellings centered on the lacrimal sac spans malformations, diverticula, dermoid/epidermoid cysts, sac inflammations/infections causing swelling without generalized sac enlargement, encephaloceles and primary epithelial tumors, as well as extrinsic tumors impinging on the sac.},
	keywords = {Aged, 80 and over, Bacteroidaceae Infections, Biomarkers, Dacryocystitis, Dacryocystorhinostomy, Diagnosis, Differential, Female, Gram-Positive Bacterial Infections, Humans, Immunohistochemistry, Lacrimal Duct Obstruction, Mucocele, Nasolacrimal Duct, Peptostreptococcus, Prevotella, Tomography, X-Ray Computed},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2012.02.003},
	author = {Perry, Lynn J P and Jakobiec, Frederick A and Zakka, Fouad R and Rubin, Peter A D}
}
@article {1364528,
	title = {Bacterial and mucopeptide concretions of the lacrimal drainage system: an analysis of 30 cases},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {28},
	number = {2},
	year = {2012},
	month = {2012 Mar-Apr},
	pages = {126-33},
	abstract = {PURPOSE: To demonstrate the histopathologic characteristics of different types of lacrimal drainage system concretions with clinical correlations. METHODS: Thirty lacrimal drainage system concretions submitted to the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary over a 2-year period were reviewed. Concretions were studied in detail using their histopathologic staining features as revealed with hematoxylin and eosin, Gomori methenamine silver, periodic acid-Schiff, iron stain, and Brown-Hopps tissue gram stain. A separate retrospective chart review was conducted for each patient to identify any clinical correlations. RESULTS: Two major forms of concretions were identified histopathologically: mucopeptide (7) and bacterial (20). Mucopeptide concretions were found exclusively within the lacrimal sac, while bacterial concretions were found chiefly in the canaliculus. A third category of "mixed" concretions with substantial mucopeptide and bacterial characteristics comprised 3 specimens. Bacterial concretions consisted of large matted masses of filamentous, presumed Actinomyces organisms that were easily identified with the Grocott{\textquoteright}s methenamine silver stain; they were frequently cocolonized at their edges with coccal bacterial forms. Mucopeptide concretions were generally devoid of cellular elements and were composed of broad bland whorls of diffusely eosinophilic, acellular, periodic acid-Schiff-positive material punctuated by lacunae. They were often cocolonized by small numbers of bacterial cocci and occasional fungi. Culture results disclosed low virulence species. All 3 types of concretions predominated in women. Patients with bacterial concretions frequently had dry eye symptoms. CONCLUSIONS: The 2 major types of lacrimal system concretions differ in their primary location and histopathologic composition. Further characterization may lead to an understanding of the mechanisms for their formation. Mucopeptide concretion is more appropriate than terms such as "dacryolith" and "mucolith," and bacterial concretion is a more appropriate term than "canaliculith," because of the absence of significant calcium or stone-like density in these masses.},
	keywords = {Actinomyces, Actinomycosis, Adult, Aged, Aged, 80 and over, Calculi, Eye Infections, Bacterial, Female, Humans, Lacrimal Apparatus Diseases, Male, Middle Aged, Mucoproteins, Nasolacrimal Duct, Retrospective Studies, Sex Factors},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31824c88a6},
	author = {Perry, Lynn J Poole and Jakobiec, Frederick A and Zakka, Fouad R}
}
@article {1814321,
	title = {Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020},
	journal = {Eye (Lond)},
	year = {2024},
	month = {2024 Mar 09},
	abstract = {BACKGROUND: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals. METHODS: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity \&lt;6/18, >=3/60) and blindness (presenting visual acuity \&lt;3/60). Estimates are age-standardized using the GBD standard population. RESULTS: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6\%) people were blind and 83.5 million (28.3\%) had MSVI due to cataract blind 60\% female, MSVI 59\% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7\%(93.1\%) whereas the age-standardized global prevalence of cataract-related blindness improved by -27.5\% and MSVI increased by 7.2\%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9\%) and Southeast Asia and Oceania (47.9\%). CONCLUSIONS: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.},
	issn = {1476-5454},
	doi = {10.1038/s41433-024-02961-1},
	author = {Pesudovs, Konrad and Lansingh, Van Charles and Kempen, John H and Tapply, Ian and Fernandes, Arthur G and Cicinelli, Maria V and Arrigo, Alessandro and Leveziel, Nicolas and Briant, Paul Svitil and Vos, Theo and Resnikoff, Serge and Taylor, Hugh R and Sedighi, Tabassom and Flaxman, Seth and Steinmetz, Jaimie and Bourne, Rupert and Vision Loss Expert Group of the Global Burden of Disease Study and GBD 2019 Blindness and Vision Impairment Collaborators}
}
@article {1452971,
	title = {The Liberfarb syndrome, a multisystem disorder affecting eye, ear, bone, and brain development, is caused by a founder pathogenic variant in thePISD gene},
	journal = {Genet Med},
	volume = {21},
	number = {12},
	year = {2019},
	month = {2019 12},
	pages = {2734-2743},
	abstract = {PURPOSE: We observed four individuals in two unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature. The phenotype precisely matched that of an individual of Azorean descent published in 1986 by Liberfarb and coworkers. METHODS: Patients underwent specialized clinical examinations (including ophthalmological, audiological, orthopedic, radiological, and developmental assessment). Exome and targeted sequencing was performed on selected individuals. Minigene constructs were assessed by quantitative polymerase chain reaction (qPCR) and Sanger sequencing. RESULTS: Affected individuals shared a 3.36-Mb region of autozygosity on chromosome 22q12.2, including a 10-bp deletion (NM_014338.3:c.904-12_904-3delCTATCACCAC), immediately upstream of the last exon of the PISD (phosphatidylserine decarboxylase) gene. Sequencing of PISD from paraffin-embedded tissue from the 1986 case revealed the identical homozygous variant. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts. CONCLUSION: We have identified the genetic etiology of the Liberfarb syndrome, affecting brain, eye, ear, bone, and connective tissue. Our work documents the migration of a rare Portuguese founder variant to two continents and highlights the link between phospholipid metabolism and bone formation, sensory defects, and cerebral development, while raising the possibility of therapeutic phospholipid replacement.},
	issn = {1530-0366},
	doi = {10.1038/s41436-019-0595-x},
	author = {Peter, Virginie G and Quinodoz, Mathieu and Pinto-Basto, Jorge and Sousa, Sergio B and Di Gioia, Silvio Alessandro and Soares, Gabriela and Ferraz Leal, Gabriela and Silva, Eduardo D and Pescini Gobert, Rosanna and Miyake, Noriko and Matsumoto, Naomichi and Engle, Elizabeth C and Unger, Sheila and Shapiro, Frederic and Superti-Furga, Andrea and Rivolta, Carlo and Campos-Xavier, Belinda}
}
@article {1511494,
	title = {The Changing Global Epidemic of HIV and Ocular Disease},
	journal = {Ocul Immunol Inflamm},
	volume = {28},
	number = {7},
	year = {2020},
	month = {2020 Oct 02},
	pages = {1007-1014},
	abstract = {: Overview of the evolving epidemiology of human immunodeficiency virus (HIV)-related ocular disease over time. : Narrative review. : HIV enhances susceptibility to opportunistic eye infections, has direct pathogenic effects, and places patients at risk of immune recovery inflammatory syndromes in previously infected eyes after starting highly-active antiretroviral therapy (HAART). Widespread availability of HAART has resulted in a decrease of infectious ocular conditions such as cytomegalovirus retinitis, toxoplasmic retinitis, squamous cell carcinoma of the conjunctiva, and microvascular retinopathy. However, large coexisting burdens of tuberculosis, herpesvirus infection and syphilis (among others) continue to contribute to the burden of ocular disease, especially in low-resource settings. Growing risks of cataract, retinopathy and retinal nerve fiber thinning can affect patients with chronic HIV on HAART; thought due to chronic inflammation and immune activation. : The changing epidemic of ocular disease in HIV-infected patients warrants close monitoring and identification of interventions that can help reduce the imminent burden of disease.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1751214},
	author = {Peters, Remco P H and Kestelyn, Philippe G and Zierhut, Manfred and Kempen, John H}
}
@article {1698336,
	title = {A2Ar-dependent PD-1+ and TIGIT+ Treg cells have distinct homing requirements to suppress autoimmune uveitis in mice},
	journal = {Mucosal Immunol},
	volume = {16},
	number = {4},
	year = {2023},
	month = {2023 Aug},
	pages = {422-431},
	abstract = {The proper function of regulatory T cells (Tregs) to suppress inflammation requires homing to the correct tissue site. Resolution of autoimmune uveitis generates distinct programmed death receptor 1 (PD-1+) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT+) Tregs in an adenosine 2A receptor (A2Ar)-dependent manner found in the spleen. Where and how these Tregs migrate from the spleen to prevent uveitis is not known. In this work, we show that A2Ar-dependent Tregs migrated to the eye and secondary lymphoid tissue and expressed chemokine receptor (CCR)6 and CCR7. Suppression of autoimmune uveitis required CCR6 and CCR7 expression for TIGIT+ Tregs but not PD-1+ Tregs. Moreover, stimulation of A2Ar on T cells from patients showed a decreased capacity to induce TIGIT+ Tregs that expressed CCR6 or CCR7, and PD-1+ Treg that expressed CCR6. This work provides a mechanistic understanding of the homing requirements of each of these Treg populations. Importantly, this work is clinically relevant because patients with chronic autoimmune uveitis are unable to induce the Treg populations identified in mice that home to the target tissue.},
	keywords = {Animals, Autoimmune Diseases, Inflammation, Mice, Receptor, Adenosine A2A, Receptors, CCR7, Receptors, Immunologic, T-Lymphocytes, Regulatory, Uveitis},
	issn = {1935-3456},
	doi = {10.1016/j.mucimm.2023.04.005},
	author = {Peters, Kayleigh and McDonald, Trisha and Muhammad, Fauziyya and Walsh, Marisa and Drenen, Kayla and Montieth, Alyssa and Stephen Foster, C and Lee, Darren J}
}
@article {1263376,
	title = {Cataract Surgery in Patients with Diabetes: Management Strategies},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 16},
	pages = {1-8},
	abstract = {Diabetes is a chronic systemic disease that affects nearly one in eight adults worldwide. Ocular complications, such as cataract, can lead to significant visual impairment. Among the worldwide population, cataract is the leading cause of blindness, and patients with diabetes have an increased incidence of cataracts which mature earlier compared to the rest of the population. Cataract surgery is a common and safe procedure, but can be associated with vision-threatening complications in the diabetic population, such as diabetic macular edema, postoperative macular edema, diabetic retinopathy progression, and posterior capsular opacification. This article is a brief review of diabetic cataract and complications associated with cataract extraction in this population of patients.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353817},
	author = {Peterson, Scott R and Silva, Paolo A and Murtha, Timothy J and Sun, Jennifer K}
}
@article {1608598,
	title = {Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve},
	journal = {J Neurosci},
	volume = {41},
	number = {41},
	year = {2021},
	month = {2021 Oct 13},
	pages = {8508-8531},
	abstract = {Axon regenerative failure in the mature CNS contributes to functional deficits following many traumatic injuries, ischemic injuries, and neurodegenerative diseases. The complement cascade of the innate immune system responds to pathogen threat through inflammatory cell activation, pathogen opsonization, and pathogen lysis, and complement is also involved in CNS development, neuroplasticity, injury, and disease. Here, we investigated the involvement of the classical complement cascade and microglia/monocytes in CNS repair using the mouse optic nerve injury (ONI) model, in which axons arising from retinal ganglion cells (RGCs) are disrupted. We report that central complement C3 protein and mRNA, classical complement C1q protein and mRNA, and microglia/monocyte phagocytic complement receptor CR3 all increase in response to ONI, especially within the optic nerve itself. Importantly, genetic deletion of C1q, C3, or CR3 attenuates RGC axon regeneration induced by several distinct methods, with minimal effects on RGC survival. Local injections of C1q function-blocking antibody revealed that complement acts primarily within the optic nerve, not retina, to support regeneration. Moreover, C1q opsonizes and CR3+ microglia/monocytes phagocytose growth-inhibitory myelin debris after ONI, a likely mechanism through which complement and myeloid cells support axon regeneration. Collectively, these results indicate that local optic nerve complement-myeloid phagocytic signaling is required for CNS axon regrowth, emphasizing the axonal compartment and highlighting a beneficial neuroimmune role for complement and microglia/monocytes in CNS repair.SIGNIFICANCE STATEMENT Despite the importance of achieving axon regeneration after CNS injury and the inevitability of inflammation after such injury, the contributions of complement and microglia to CNS axon regeneration are largely unknown. Whereas inflammation is commonly thought to exacerbate the effects of CNS injury, we find that complement proteins C1q and C3 and microglia/monocyte phagocytic complement receptor CR3 are each required for retinal ganglion cell axon regeneration through the injured mouse optic nerve. Also, whereas studies of optic nerve regeneration generally focus on the retina, we show that the regeneration-relevant role of complement and microglia/monocytes likely involves myelin phagocytosis within the optic nerve. Thus, our results point to the importance of the innate immune response for CNS repair.},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.0555-21.2021},
	author = {Peterson, Sheri L and Li, Yiqing and Sun, Christina J and Wong, Kimberly A and Leung, Kylie S and de Lima, Silmara and Hanovice, Nicholas J and Yuki, Kenya and Beth Stevens and Benowitz, Larry I}
}
@article {1483619,
	title = {Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial},
	journal = {Ophthalmology},
	volume = {127},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {14-26},
	abstract = {PURPOSE: To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy. DESIGN: Multicenter, randomized, double-masked, vehicle-controlled trial. PARTICIPANTS: Patients with neurotrophic persistent epithelial defect with or without stromal thinning. METHODS: The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. MAIN OUTCOME MEASURES: The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (\&lt;0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week\&nbsp;8. RESULTS: Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2\%), 16 of 23 cenegermin-treated patients (69.6\%) achieved less than 0.5 mm of lesion staining (+40.4\%; 95\% confidence interval [CI], 14.2\%-66.6\%; P\&nbsp;= 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7\%), 15 of 23 cenegermin-treated patients (65.2\%) achieved 0 mm of lesion staining and no other residual staining (+48.6\%; 95\% CI, 24.0\%-73.1\%; P \&lt; 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. CONCLUSIONS: Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.08.020},
	author = {Pflugfelder, Stephen C and Massaro-Giordano, Mina and Perez, Victor L and Hamrah, Pedram and Deng, Sophie X and Espandar, Ladan and Foster, C Stephen and Affeldt, John and Seedor, John A and Afshari, Natalie A and Chao, Wendy and Allegretti, Marcello and Mantelli, Flavio and Dana, Reza}
}
@article {988001,
	title = {The potential of spectral domain optical coherence tomography imaging based retinal biomarkers.},
	journal = {Int J Retina Vitreous},
	volume = {3},
	year = {2017},
	pages = {1},
	abstract = {BACKGROUND: Biomarker", a merged word of "biological marker", refers to a broad subcategory of medical signs that objectively indicate the state of health, and well-being of an individual. Biomarkers hold great promise for personalized medicine as information gained from diagnostic or progression markers can be used to tailor treatment to the individual for highly effective intervention in the disease process. Optical coherence tomography (OCT) has proved useful in identifying various biomarkers in ocular and systemic diseases. MAIN BODY: Spectral domain optical coherence tomography imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression, and monitoring treatment response. The aim of this review article is to analyze various OCT based imaging biomarkers and their potential to be considered as surrogate endpoints for diabetic retinopathy, age related macular degeneration, retinitis pigmentosa and vitreomacular interface disorder. These OCT based surrogate markers have been classified as retinal structural alterations (macular central subfield thickness and cube average thickness); retinal ultrastructural alterations (disruption of external limiting membrane and ellipsoid zone, thinning of retinal nerve fiber layer and ganglion cell layer); intraretinal microangiopathic changes; choroidal surrogate endpoints; and vitreoretinal interface endpoints. CONCLUSION: OCT technology is changing very quickly and throughout this review there are some of the multiple possibilities that OCT based imaging biomarkers will be more useful in the near future for diagnosis, prognosticating disease progression and as endpoint in clinical trials.},
	doi = {10.1186/s40942-016-0054-7},
	author = {Phadikar, Prateep and Saxena, Sandeep and Ruia, Surabhi and Lai, Timothy Y Y and Meyer, Carsten H and Eliott, Dean}
}
@article {1629445,
	title = {Ophthalmic trauma: the top 100 cited articles in Ophthalmology journals},
	journal = {Eye (Lond)},
	volume = {36},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {2328-2333},
	abstract = {OBJECTIVES: To analyze the top 100 cited papers on ophthalmic trauma. METHODS: A literature search of Ophthalmology journals within the ISI Web of Science database for the most cited papers related to ophthalmic trauma. RESULTS: The most cited articles were published between 1943 and 2013, the greatest number being published in 2000. Ophthalmology (45), Archives of Ophthalmology (17), and the American Journal of Ophthalmology (15) published most of the articles. The institutions with the highest number of publications were Wilmer Eye Institute (10) and Massachusetts Eye and Ear Infirmary (7). Sixty-seven percent of the articles originated from the USA. The most common type of trauma studied was non-open-globe injuries and the most frequent topic studied were pathological conditions secondary to trauma (34), particularly endophthalmitis (8), and optic neuropathy (6). Articles presenting a standardized classification system for eye injury received the highest average of citations per publication. Types of research most frequently cited were observational clinical studies (62) and epidemiological studies (30); the least frequent were clinical trials (2). CONCLUSION: This bibliographic study provides a historical perspective of the literature and identifies trends within the most highly influential papers on ophthalmic trauma. Many of these articles emerged within the past three decades and came from Ophthalmology journals that remain high impact to this day. Clinical trials have been difficult to conduct and are lacking, reflecting a critical need in ophthalmic trauma research, as most of our understanding of ophthalmic trauma comes from observational and epidemiological studies.},
	keywords = {Bibliometrics, Databases, Factual, Eye Injuries, Humans, Ophthalmology, Periodicals as Topic},
	issn = {1476-5454},
	doi = {10.1038/s41433-021-01871-w},
	author = {Pham, Alex T and Whitescarver, Todd D and Beatson, Bradley and Purt, Boonkit and Yonekawa, Yoshihiro and Shah, Ankoor S and Colyer, Marcus H and Woreta, Fasika A and Justin, Grant A}
}
@article {1661817,
	title = {Strabismus Surgery in Orthophoric Patients With Symptomatic, Asymmetric Vertical or Horizontal Incomitance},
	journal = {Am J Ophthalmol},
	volume = {249},
	year = {2023},
	month = {2023 May},
	pages = {29-38},
	abstract = {PURPOSE: To report the indications, operative strategies, and surgical outcomes of patients who undergo vertical and horizontal rectus muscle surgery for incomitant strabismus despite being orthophoric in primary gaze. DESIGN: Retrospective, interventional case series. METHODS: The setting for this study was an academic practice at Boston Children{\textquoteright}s Hospital. The patient population comprised 8 orthophoric patients who underwent strabismus surgery to treat vertical/horizontal incomitance. Observation procedures included review of surgical strategies, strabismus measurements in diagnostic gaze positions, and development of postoperative diplopia. The main outcome measures were preserved single vision in primary gaze, comitance, reoperation rate, and patient/surgeon satisfaction. RESULTS: Surgical strategies included the following: (1) simultaneous recession of ipsilateral antagonist rectus muscles; (2) recession or resection of 1 rectus muscle with balancing surgery on the fellow eye; (3) restricting the range of 1 muscle (combined resection and recession or posterior fixation suture); and (4) creating an acceptable deviation in primary gaze. Mean follow-up was 5.4 months (median, 2 months; range, 2-25 months). No patient had new-onset primary gaze diplopia. The median incomitance improved by 9.5 prism diopters. No patient required additional surgery. Patient satisfaction and surgeon assessment of outcomes were high. CONCLUSIONS: Although the risk of operating on orthophoric patients with incomitant strabismus may discourage surgeons from offering treatment, the use of specific strategies to address incomitance can preserve alignment in primary gaze while improving patient satisfaction. These strategies may also benefit patients with incomitant strabismus that is symptomatic in primary gaze.},
	keywords = {Child, Diplopia, Humans, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Retrospective Studies, Strabismus, Treatment Outcome, Vision, Binocular},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.12.019},
	author = {Phanphruk, Warachaya and Hennein, Lauren and Hunter, David G}
}
@article {1078801,
	title = {Sedated suture adjustment in children undergoing adjustable-suture strabismus surgery},
	journal = {J AAPOS},
	year = {2017},
	month = {2017 May 19},
	abstract = {PURPOSE: To study methods and adverse events of postoperative, sedated suture adjustment after strabismus surgery in the post-anesthesia care unit (PACU). METHODS: We reviewed the postoperative experience of all children <=18 years of age undergoing adjustable suture strabismus surgery at Boston Children{\textquoteright}s Hospital over a 3-year period. Time in the hospital, adverse events, and surgical outcomes were reviewed to evaluate safety and healthcare resource utilization. RESULTS: Of 356 patients, 113 required suture adjustment in the PACU, including 24 adjusted while awake and 89 adjusted under sedation. For sedation, sequential boluses of propofol were administered until adjustment was complete. Complete data from the sedated adjustment was available in 76 patients. The median initial bolus was 30 mg; the median total propofol rate was 273 mcg/kg/min. Twelve patients (16\%) required only a single bolus of propofol. Of remaining 64 patients, median time from initial to final propofol dose was 7 minutes. Median anesthesiologist time in the PACU was 13 minutes. In the sedated adjustment group, there were no clinically significant adverse events, and the pain score never exceeded 6 (of a possible 10). Median duration of PACU stay was shortest in the group not requiring adjustment. CONCLUSIONS: Sedated suture adjustment allows for fine-tuning of postoperative binocular alignment in children and uncooperative adults. No adverse events were observed in our study group, but the procedure does increase the time patients spend in the hospital. This work will inform disclosure of risks and benefits of sedated adjustment while allowing for more accurate assessment of the cost and quality of adjustable sutures in children.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2017.05.010},
	author = {Phanphruk, Warachaya and Alkharashi, Maan and Bilge, Aykut and Hunter, David G}
}
@article {1789106,
	title = {Ocular Cicatricial Pemphigoid With IgM-Positive Biopsy},
	journal = {Cornea},
	volume = {42},
	number = {12},
	year = {2023},
	month = {2023 Dec 01},
	pages = {1503-1505},
	abstract = {PURPOSE: The aim of this study was to investigate the prevalence of IgM along the basement membrane zone (BMZ) of patients with ocular cicatricial pemphigoid (OCP) and the outcomes of these patients with immunomodulatory therapy. METHODS: This study is a retrospective chart review of patients with conjunctival biopsy-proven OCP. Clinical data, including the presence of linear IgM deposition along the BMZ on either direct immunofluorescence or avidin-biotin complex immunohistochemistry, were recorded. Response to IMT was also recorded. RESULTS: A total of 817 patients with documented conjunctival biopsies were identified, with 93 (11.4\%) positive for OCP with linear IgM deposition along the BMZ. Forty-six patients with sufficient follow-up were evaluated for clinical outcomes, with 35 (76.1\%) able to achieve durable remission an average of 24.3 months after initiation of IMT. Most of these patients, 82.9\%, were able to achieve durable remission with first-line antimetabolite therapy. Three patients were identified with solely IgM-positive conjunctival biopsies. CONCLUSIONS: Our study suggests that IgM positivity is seen in a minority of patients with OCP and that outcomes are comparable for these patients to the general OCP patient population.},
	keywords = {Biopsy, Conjunctiva, Humans, Immunoglobulin M, Pemphigoid, Benign Mucous Membrane, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003235},
	author = {Philip, Andrew M and Stephenson, Andrew and Al-Dabbagh, Alaa and Ramezani, Koosha and Fernandez-Santos, Carla C and Foster, C Stephen}
}
@article {1677676,
	title = {Ocular Mucus Membrane Pemphigoid: A Primary Versus Secondary Entity},
	journal = {Cornea},
	volume = {42},
	number = {3},
	year = {2023},
	month = {2023 Mar 01},
	pages = {280-283},
	abstract = {PURPOSE: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). METHODS: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens-Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. RESULTS: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2\%) being positive. One hundred thirty-nine patients (21.5\%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4\%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3\%) had only 1 such condition, 35 (6.9\%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9\% of patients with sufficient follow-up. CONCLUSIONS: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.},
	keywords = {Conjunctiva, Eyelid Diseases, Humans, Mucus, Pemphigoid, Benign Mucous Membrane, Pemphigoid, Bullous, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003056},
	author = {Philip, Andrew M and Fernandez-Santos, Carla C and Ramezani, Koosha and Dolinko, Andrew H and Manhapra, Ambika and Look-Why, Sydney and Chang, Peter Y and Foster, C Stephen and Anesi, Stephen D}
}
@article {1773496,
	title = {Ocular Inflammatory Complications of Treatment for Metastatic Melanoma},
	journal = {Ocul Immunol Inflamm},
	volume = {31},
	number = {8},
	year = {2023},
	month = {2023 Oct},
	pages = {1669-1673},
	abstract = {PURPOSE: To characterize various ocular inflammatory complications arising from metastatic cutaneous melanoma therapies and their management. METHODS: Retrospective case series of patients who were referred to a tertiary uveitis practice for ophthalmic exam All patients received targeted metastatic cutaneous melanoma treatment, including BRAF/MEK inhibitors and various immunotherapies. RESULTS: 109 patients were identified, with 43 (39.4\%) having 65 definitive instances of OIAE. Sixteen different OIAE were identified. Ipilimumab monotherapy and ipilimumab/nivolumab combination therapy were most commonly associated. Anterior uveitis was the most common OIAE (18/65, 27.7\%). Thirty patients (69.8\%) were managed with observation or topical steroid therapy. Only 4 patients required further therapies for OIAE, with one patient not attaining resolution. CONCLUSIONS AND RELEVANCE: While a broad range of OIAE was identified, most were not vision-threatening and did not require discontinuation of the associated therapy.},
	keywords = {Humans, Ipilimumab, Melanoma, Protein Kinase Inhibitors, Retrospective Studies, Skin Neoplasms},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2098147},
	author = {Philip, Andrew M and Anesi, Stephen D and Foster, C Stephen and Chang, Peter}
}
@article {369011,
	title = {The Status of RPE65 Gene Therapy Trials: Safety and Efficacy.},
	journal = {Cold Spring Harb Perspect Med},
	year = {2015},
	month = {2015 Jan 29},
	abstract = {Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective. The successful clinical trials of gene augmentation therapy for retinal degeneration caused by mutations in the RPE65 gene sets the stage for broad application of gene therapy to treat retinal degenerative disorders.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a017285},
	author = {Pierce, Eric A and Bennett, Jean}
}
@article {1470973,
	title = {Binocular Treatment of Amblyopia: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {127},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {261-272},
	abstract = {PURPOSE: To review the published literature assessing the efficacy of binocular therapy for the treatment of amblyopia compared with standard treatments. METHODS: Literature searches with no date restrictions and limited to the English language were conducted in January 2018 and updated in April 2019 in the PubMed database and the Cochrane Library database with no restrictions. The search yielded 286 citations, and the full text of 50 articles was reviewed. Twenty articles met the inclusion criteria for this assessment and were assigned a level of evidence rating by the panel methodologist. Six studies were rated level I, 1 study was rated level II, and 13 studies were rated level III because of the impact on the development and popularization of this technology. RESULTS: Two of the level I and II studies reviewed described a significant improvement in visual acuity in the binocular group versus standard patching standard treatment (the total number of patients in these 2 studies was 147). However, the 5 studies that failed to show a visual improvement from binocular therapy compared with standard treatments were larger and more rigorously designed (the total number of patients in these 5 studies was 813). Level I and II studies also failed to show a significant improvement over baseline in sensory status, including depth of suppression and stereopsis of those treated with binocular therapy. Several smaller level III case series (total number of patients in these 13 studies was 163) revealed more promising results than the binocular treatments studied in the level I and II studies, especially using treatments that are more engaging and are associated with better compliance. CONCLUSIONS: There is no level I evidence to support the use of binocular treatment as a substitute for current therapies for amblyopia (including patching and optical treatment). Furthermore, 2 large randomized controlled trials showed inferior performance compared with standard patching treatment. On the basis of this review of the published literature, binocular therapy cannot be recommended as a replacement for standard amblyopia therapy. However, more research is needed to determine the potential benefits of proposed binocular treatments in the future.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.08.024},
	author = {Pineles, Stacy L and Aakalu, Vinay K and Hutchinson, Amy K and Galvin, Jennifer A and Heidary, Gena and Binenbaum, Gil and VanderVeen, Deborah K and Lambert, Scott R}
}
@article {1651065,
	title = {The Pediatric Optic Neuritis Prospective Outcomes Study: Two-Year Results},
	journal = {Ophthalmology},
	volume = {129},
	number = {8},
	year = {2022},
	month = {2022 08},
	pages = {856-864},
	abstract = {PURPOSE: Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. DESIGN: Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. PARTICIPANTS: A total of 28 (64\%) of 44 children initially enrolled in PON1 (age 3-\&lt;16 years) who completed their 2-year study visit. METHODS: Participants were treated at the investigator{\textquoteright}s discretion. MAIN OUTCOMES MEASURES: Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. RESULTS: A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5-15); 46\% were female, and 68\% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n\&nbsp;= 11, 39\%), myelin oligodendrocyte glycoprotein-associated demyelination (n\&nbsp;= 8, 29\%), multiple sclerosis (MS) (n\&nbsp;= 4,14\%), neuromyelitis optica spectrum disease (NMOSD) (n\&nbsp;= 3, 11\%), and acute disseminated encephalomyelitis (n\&nbsp;= 2, 7\%). Two participants (7\%; 95\% confidence interval [CI], 1-24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7\%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (\~{}20/125), improving to 0.14 logMAR (\~{}20/25-2) at 6 months, 0.12 logMAR (\~{}20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95\% CI,\&nbsp;-0.08 to 0.3 [20/20+1-20/40-1]). Twenty-four participants (79\%) had age-normal VA at 2 years (95\% CI, 60-90); 21 participants (66\%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n\&nbsp;= 2 participants, 3 eyes), MS (n\&nbsp;= 2 participants, 2 eyes), and isolated ON (n\&nbsp;= 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (\~{}20/500-2), improving to 0.78 logMAR (\~{}20/125+2) at 6 months, 0.69 logMAR (\~{}20/100+1) at 1 year, and 0.68 logMAR (\~{}20/100+2) at 2 years (95\% CI, 0.48-0.88 [20/50+1-20/150-1]). CONCLUSIONS: Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18\%) of the participants (3 relapses and 2 new episodes).},
	keywords = {Adolescent, Child, Child, Preschool, Female, Humans, Male, Multiple Sclerosis, Myelin-Oligodendrocyte Glycoprotein, Neoplasm Recurrence, Local, Neuromyelitis Optica, Optic Neuritis, Prospective Studies, Retrospective Studies, Vision Disorders},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.03.021},
	author = {Pineles, Stacy L and Henderson, Robert J and Repka, Michael X and Heidary, Gena and Liu, Grant T and Waldman, Amy T and Borchert, Mark S and Khanna, Sangeeta and Graves, Jennifer S and Collinge, Janine E and Conley, Julie A and Davis, Patricia L and Kraker, Raymond T and Cotter, Susan A and Holmes, Jonathan M and Pediatric Eye Disease Investigator Group}
}
@article {1282146,
	title = {Atropine for the Prevention of Myopia Progression in Children: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {124},
	number = {12},
	year = {2017},
	month = {2017 Dec},
	pages = {1857-1866},
	abstract = {PURPOSE: To review the published literature on the efficacy of topical atropine for the prevention of myopic progression in children. METHODS: Literature searches were last conducted in December 2016 in the PubMed database with no date restrictions, but were limited to studies published in English, and in the Cochrane Library database without any restrictions. The combined searches yielded 98 citations, 23 of which were reviewed in full text. Of these, 17 articles were deemed appropriate for inclusion in this assessment and subsequently were assigned a level of evidence rating by the panel methodologist. RESULTS: Seventeen level I, II, and III studies were identified. Most of the studies reported less myopic progression in children treated with atropine compared with various control groups. All 8 of the level I and II studies that evaluated primarily myopic progression revealed less myopic progression with atropine (myopic progression ranging from 0.04{\textpm}0.63 to 0.47{\textpm}0.91 diopters (D)/year) compared with control participants (myopic progression ranging from 0.38{\textpm}0.39 to 1.19{\textpm}2.48 D/year). In studies that evaluated myopic progression after cessation of treatment, a rebound effect was noted. Several studies evaluated the optimal dosage of atropine with regard to myopic progression, rebound after treatment cessation, and minimization of side effects. Lower dosages of atropine (0.5\%, 0.1\%, and 0.01\%) were found to be slightly less effective during treatment periods of 1 to 2 years, but they were associated with less rebound myopic progression (for atropine 0.01\%, mean myopic progression after treatment cessation of 0.28{\textpm}0.33 D/year, compared with atropine 0.5\%, 0.87{\textpm}0.52 D/year), fewer side effects, and similar long-term results for myopic progression after the study period and rebound effect were considered. The most robust and well-designed studies were carried out in Asian populations. Studies involving patients of other ethnic backgrounds failed to provide sufficient evidence of an effect of atropine on myopic progression. CONCLUSIONS: Level I evidence supports the use of atropine to prevent myopic progression. Although there are reports of myopic rebound after treatment is discontinued, this seems to be minimized by using low doses (especially atropine 0.01\%).},
	keywords = {Academies and Institutes, Atropine, Child, Child, Preschool, Databases, Factual, Disease Progression, Female, Humans, Male, Mydriatics, Myopia, Ophthalmology, Technology Assessment, Biomedical, Treatment Outcome, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.05.032},
	author = {Pineles, Stacy L and Kraker, Raymond T and VanderVeen, Deborah K and Hutchinson, Amy K and Galvin, Jennifer A and Wilson, Lorri B and Lambert, Scott R}
}
@article {1580492,
	title = {Contemporaneous Risk Factors for Visual Acuity in Non-Infectious Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Feb 23},
	pages = {1-8},
	abstract = {INTRODUCTION: We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5\&nbsp;years in a subspecialty noninfectious uveitis population. METHODS: Retrospective data from 5,530 noninfectious uveitis patients were abstracted by expert reviewers, and contemporaneous associations of VA with demographic and clinical factors were modeled. RESULTS: Patients were a median of 41\&nbsp;years old, 65\% female, and 73\% white. Eyes diagnosed >=5\&nbsp;years prior to cohort entry had worse VA (-1.2 lines) than those diagnosed \&lt;6\&nbsp;months prior, and eyes with cataract surgery performed prior to entry had worse VA (-5.9 lines) than those performed during follow-up. Vitreous haze (-4.2 lines for 3+\&nbsp;vs quiet), hypotony (-2.5 lines for <=5 mm Hg vs 6-23 mm Hg), and CNV (-1.8 lines) all were strongly associated with reduced VA. CONCLUSION: Factors associated with reduced VA included well-known structural complications, and lack of subspecialty care during cataract surgery.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1828493},
	author = {Pistilli, Maxwell and Gangaputra, Sapna S and Pujari, Siddharth S and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Bhatt, Nirali P and Foster, C Stephen and Begum, Hosne and Fitzgerald, Tonetta D and Dreger, Kurt A and Kempen, John H}
}
@article {1478337,
	title = {Visual Acuity Outcome over Time in Non-Infectious Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2019},
	month = {2019 Dec 10},
	pages = {1-8},
	abstract = {: We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population.: Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up.: Patients were a median of 41 years old, 65\% female, and 73\% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each \&lt; .001), then remained stable, except posterior uveitis mean VA worsened to initial levels.: Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2019.1687733},
	author = {Pistilli, Maxwell and Joffe, Marshall M and Gangaputra, Sapna S and Pujari, Siddharth S and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Bhatt, Nirali P and Foster, C Stephen and Begum, Hosne and Fitzgerald, Tonetta D and Dreger, Kurt A and Altaweel, Michael M and Holbrook, Janet T and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Research Group}
}
@article {1658663,
	title = {Neurodegeneration Markers Galectin-3 and Apolipoprotein E Are Elevated in the Aqueous Humor of Eyes With Glaucoma},
	journal = {Transl Vis Sci Technol},
	volume = {11},
	number = {11},
	year = {2022},
	month = {2022 Nov 01},
	pages = {1},
	abstract = {PURPOSE: Galectin-3 (Gal-3) and apolipoprotein E (APOE) are markers of activated microglia in neurodegenerative diseases of the central nervous system, whose targeting is protective in mouse models of glaucoma. In this study, we examined levels of Gal-3 and APOE in human aqueous humor (AH) and defined their clinical associations with glaucoma. METHODS: We collected AH from 59 glaucoma patients and 15 controls at the start of planned ophthalmic surgery. Gal-3 and APOE levels were quantified by enzyme-linked immunosorbent assay. Total protein in AH was quantified by bicinchoninic acid assay. Significant associations between Gal-3, APOE, and clinical covariates were defined using univariate and multivariate linear regression models. RESULTS: Gal-3 and APOE levels were significantly elevated in the AH of glaucoma patients compared to controls (P = 0.004 and P \&lt; 0.001, respectively). Gal-3 and APOE were positively correlated across the entire cohort (r = 0.65, P = 6.2E-9). No association was observed between Gal-3 and total protein or APOE and total protein (P = 0.35 and P = 0.50, respectively), indicating that their levels were not increased in glaucomatous AH due to nonspecific protein accumulation. Multivariate linear regression modeling revealed significant associations between Gal-3 and maximum recorded intraocular pressure (P = 0.009) and between APOE and number of past ophthalmic surgeries (P = 0.031). CONCLUSIONS: We demonstrate that Gal-3 and APOE are significantly elevated in the AH of eyes with glaucoma and are associated with a history of poorly controlled disease. TRANSLATIONAL RELEVANCE: Gal-3 and APOE in AH may inform clinical decision-making as quantifiable readouts of microglial activation in eyes with glaucoma.},
	keywords = {Animals, Apolipoproteins E, Aqueous Humor, Biomarkers, Galectin 3, Glaucoma, Glaucoma, Open-Angle, Humans, Mice},
	issn = {2164-2591},
	doi = {10.1167/tvst.11.11.1},
	author = {Pitts, Kristen M and Neeson, Cameron E and Hall, Nathan E and Lin, Jonathan B and Falah, Henisk K and Wang, Silas L and Lo, Kristine T and Song, Christian E and Margeta, Milica A and Sol{\'a}-Del Valle, David A}
}
@article {1709811,
	title = {Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity: Development and Validation of the Revised DIGIROP Clinical Decision Support Tool},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {8},
	year = {2023},
	month = {2023 Aug 01},
	pages = {716-724},
	abstract = {IMPORTANCE: The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants. OBJECTIVE: To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023. MAIN OUTCOMES AND MEASURES: Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95\% CI were the main measures. Internal and external validations were performed. RESULTS: Of 11 139 screened infants, 5071 (45.5\%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29\%), treatment was given in 599 (5\%), 7228 (65\%) had PND less than 14 days, 2308 (21\%) had PND for 14 days or more, and 1603 (14\%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P \&lt; .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, -0.9 weeks; 95\% CI, -1.5 to -0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95\% CI, 1.62-2.10; P \&lt; .001) and of severe ROP requiring treatment (aOR, 2.20; 95\% CI, 1.73-2.80; P \&lt; .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100\% sensitivity (95\% CI, 99.4-100). The specificity was 46.6\% (95\% CI, 45.6-47.5) for the prescreen model and 76.9\% (95\% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100\% sensitivity on a validation subset (G-ROP: sensitivity, 100\%; 95\% CI, 93-100; DIGIROP prescreen: sensitivity, 100\%; 95\% CI, 93-100; DIGIROP screen: sensitivity, 100\%; 95\% CI, 93-100), whereas WINROP showed 89\% sensitivity (95\% CI, 77-96). Specificity for each prediction model was 29\% (95\% CI, 22-36) for G-ROP, 38\% (95\% CI, 32-46) for DIGIROP prescreen, 53\% (95\% CI, 46-60) for DIGIROP screen at 10 weeks, and 46\% (95\% CI, 39-53) for WINROP. CONCLUSION AND RELEVANCE: Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.},
	keywords = {Decision Support Systems, Clinical, Female, Gestational Age, Humans, Infant, Infant, Newborn, Male, Neonatal Screening, Parenteral Nutrition, Prognosis, Retinopathy of Prematurity, Retrospective Studies, Risk Factors},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.2336},
	author = {Pivodic, Aldina and Holmstr{\"o}m, Gerd and Smith, Lois E H and H{\r a}rd, Anna-Lena and L{\"o}fqvist, Chatarina and Al-Hawasi, Abbas and Larsson, Eva and Lundgren, Pia and Gr{\"a}nse, Lotta and Tornqvist, Kristina and Wallin, Agneta and Johansson, Helena and Albertsson-Wikland, Kerstin and Nilsson, Staffan and Hellstr{\"o}m, Ann}
}
@article {1635644,
	title = {Validation of DIGIROP models and decision support tool for prediction of treatment for retinopathy of prematurity on a contemporary Swedish cohort},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {1132-1138},
	abstract = {BACKGROUND/AIMS: Retinopathy of prematurity (ROP) is currently diagnosed through repeated eye examinations to find the low percentage of infants that fulfil treatment criteria to reduce vision loss. A prediction model for severe ROP requiring treatment that might sensitively and specifically identify infants that develop severe ROP, DIGIROP-Birth, was developed using birth characteristics. DIGIROP-Screen additionally incorporates first signs of ROP in different models over time. The aim was to validate DIGIROP-Birth, DIGIROP-Screen and their decision support tool on a contemporary Swedish cohort. METHODS: Data were retrieved from the Swedish national registry for ROP (2018-2019) and two Swedish regions (2020), including 1082 infants born at gestational age (GA) 24 to \&lt;31 weeks. The predictors were GA at birth, sex, standardised birth weight and age at the first sign of ROP. The outcome was ROP treatment. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) with 95\% CI were described. RESULTS: For DIGIROP-Birth, the AUC was 0.93 (95\% CI 0.90 to 0.95); for DIGIROP-Screen, it ranged between 0.93 and 0.97. The specificity was 49.9\% (95\% CI 46.7 to 53.0) and the sensitivity was 96.5\% (95\% CI 87.9 to 99.6) for the tool applied at birth. For DIGIROP-Screen, the cumulative specificity ranged between 50.0\% and 78.7\%. One infant with Beckwith-Wiedemann syndrome who fulfilled criteria for ROP treatment and had no missed/incomplete examinations was incorrectly flagged as not needing screening. CONCLUSIONS: DIGIROP-Birth and DIGIROP-Screen showed high predictive ability in a contemporary Swedish cohort. At birth, 50\% of the infants born at 24 to \&lt;31 weeks of gestation were predicted to have low risk of severe ROP and could potentially be released from ROP screening examinations. All routinely screened treated infants, excluding those screened for clinical indications of severe illness, were correctly flagged as needing ROP screening.},
	keywords = {Birth Weight, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Premature, Neonatal Screening, Retinopathy of Prematurity, Retrospective Studies, Risk Factors, Sweden},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-320738},
	author = {Pivodic, Aldina and Smith, Lois E H and H{\r a}rd, Anna-Lena and L{\"o}fqvist, Chatarina and Almeida, Ana Catarina and Al-Hawasi, Abbas and Larsson, Eva and Lundgren, Pia and Sunnqvist, Birgitta and Tornqvist, Kristina and Wallin, Agneta and Holmstrom, Gerd and Gr{\"a}nse, Lotta}
}
@article {1593847,
	title = {Development and validation of a new clinical decision support tool to optimize screening for retinopathy of prematurity},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {1573-1580},
	abstract = {BACKGROUND/AIMS: Prematurely born infants undergo costly, stressful eye examinations to uncover the small fraction with retinopathy of prematurity (ROP) that needs treatment to prevent blindness. The aim was to develop a prediction tool (DIGIROP-Screen) with 100\% sensitivity and high specificity to safely reduce screening of those infants not needing treatment. DIGIROP-Screen was compared with four other ROP models based on longitudinal weights. METHODS: Data, including infants born at 24-30 weeks of gestational age (GA), for DIGIROP-Screen development (DevGroup, N=6991) originate from the Swedish National Registry for ROP. Three international cohorts comprised the external validation groups (ValGroups, N=1241). Multivariable logistic regressions, over postnatal ages (PNAs) 6-14 weeks, were validated. Predictors were birth characteristics, status and age at first diagnosed ROP and essential interactions. RESULTS: ROP treatment was required in 287 (4.1\%)/6991 infants in DevGroup and 49 (3.9\%)/1241 in ValGroups. To allow 100\% sensitivity in DevGroup, specificity at birth was 53.1\% and cumulatively 60.5\% at PNA 8 weeks. Applying the same cut-offs in ValGroups, specificities were similar (46.3\% and 53.5\%). One infant with severe malformations in ValGroups was incorrectly classified as not needing screening. For all other infants, at PNA 6-14 weeks, sensitivity was 100\%. In other published models, sensitivity ranged from 88.5\% to 100\% and specificity ranged from 9.6\% to 45.2\%. CONCLUSIONS: DIGIROP-Screen, a clinical decision support tool using readily available birth and ROP screening data for infants born GA 24-30 weeks, in the European and North American populations tested can safely identify infants not needing ROP screening. DIGIROP-Screen had equal or higher sensitivity and specificity compared with other models. DIGIROP-Screen should be tested in any new cohort for validation and if not validated it can be modified using the same statistical approaches applied to a specific clinical setting.},
	keywords = {Birth Weight, Decision Support Systems, Clinical, Gestational Age, Humans, Infant, Infant, Newborn, Neonatal Screening, Peptide Nucleic Acids, Retinopathy of Prematurity, Retrospective Studies, Risk Factors},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-318719},
	author = {Pivodic, Aldina and Johansson, Helena and Smith, Lois E H and H{\r a}rd, Anna-Lena and L{\"o}fqvist, Chatarina and Yoder, Bradley A and Hartnett, M Elizabeth and Wu, Carolyn and Br{\"u}nder, Marie-Christine and Lagr{\`e}ze, Wolf A and Stahl, Andreas and Al-Hawasi, Abbas and Larsson, Eva and Lundgren, Pia and Gr{\"a}nse, Lotta and Sunnqvist, Birgitta and Tornqvist, Kristina and Wallin, Agneta and Holmstr{\"o}m, Gerd and Albertsson-Wikland, Kerstin and Nilsson, Staffan and Hellstr{\"o}m, Ann}
}
@article {1517202,
	title = {Validation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) using retrospective clinical data},
	journal = {Acta Ophthalmol},
	volume = {99},
	number = {2},
	year = {2021},
	month = {2021 Mar},
	pages = {201-206},
	abstract = {PURPOSE: The International Neonatal Consortium recently published a proposed retinopathy of prematurity (ROP) activity scale intended for use in clinical trials after validation. The aim of this study was to validate the ROP activity scale (ROP-ActS) in a ROP screened cohort with protocol based collected data by evaluating the ability of the ROP-Act scores to predict ROP treatment. In addition, we aimed to evaluate the scale{\textquoteright}s sensitivity characteristic of disease severity by studying association with gestational age (GA) in comparison with conventionally used ROP stage and zone. METHODS: A cohort of 535 preterm infants with 3324 ROP examinations with an end-point of ROP treatment or end of screening in Gothenburg, Sweden, was included. Median GA was 28.1\&nbsp;weeks, 47.5\% were girls, and 74 (13.8\%) infants were treated for ROP. The validation was performed by estimating probabilities for ROP treatment, and by applying logistic and linear regression. RESULTS: The original ROP-ActS was overall well-ordered with respect to ability to predict ROP treatment but could be improved by re-ordering score 3 (zone II stage 1) and 5 (zone III stage 3) based on our clinical cohort data. The modified ROP-ActS was superior to ROP stage and zone in the prediction analysis of ROP treatment. Modified ROP-ActS was more strongly related to GA than currently used ROP stage, but not zone. CONCLUSION: In the studied cohort, the modified ROP-ActS could better predict ROP treatment compared to ROP stage and zone. Retinopathy of Prematurity Activity Scale (ROP-ActS) had a superior sensitivity characteristic studied through association to GA than conventionally used ROP stage.},
	issn = {1755-3768},
	doi = {10.1111/aos.14532},
	author = {Pivodic, Aldina and Nilsson, Staffan and Stahl, Andreas and Smith, Lois E H and Hellstr{\"o}m, Ann}
}
@article {1474208,
	title = {Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Nov 07},
	pages = {1-9},
	abstract = {Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95\% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6\% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8\%) were treated for ROP, including 142 (40.1\%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks{\textquoteright} GA showed high predictive ability for the model overall (AUC, 0.90 [95\% CI, 0.89-0.92] for internal validation, 0.94 [95\% CI, 0.90-0.98] for temporal validation, 0.87 [95\% CI, 0.84-0.89] for US external validation, and 0.90 [95\% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children{\textquoteright}s Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks{\textquoteright} GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.4502},
	author = {Pivodic, Aldina and H{\r a}rd, Anna-Lena and L{\"o}fqvist, Chatarina and Smith, Lois E H and Wu, Carolyn and Br{\"u}nder, Marie-Christine and Lagr{\`e}ze, Wolf A and Stahl, Andreas and Holmstr{\"o}m, Gerd and Albertsson-Wikland, Kerstin and Johansson, Helena and Nilsson, Staffan and Hellstr{\"o}m, Ann}
}
@article {1360119,
	title = {Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control},
	journal = {Diabetes},
	volume = {68},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {441-456},
	abstract = {To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts ( = 3,246) and seven African American cohorts ( = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a value \&lt;1 {\texttimes} 10 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like () was associated with DR in European discovery cohorts ( = 2.1 {\texttimes} 10), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein-protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity ( = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR.},
	issn = {1939-327X},
	doi = {10.2337/db18-0567},
	author = {Pollack, Samuela and Igo, Robert P and Jensen, Richard A and Christiansen, Mark and Li, Xiaohui and Cheng, Ching-Yu and Ng, Maggie C Y and Smith, Albert V and Rossin, Elizabeth J and Segr{\`e}, Ayellet V and Davoudi, Samaneh and Tan, Gavin S and Chen, Yii-Der Ida and Kuo, Jane Z and Dimitrov, Latchezar M and Stanwyck, Lynn K and Meng, Weihua and Hosseini, S Mohsen and Imamura, Minako and Nousome, Darryl and Kim, Jihye and Hai, Yang and Jia, Yucheng and Ahn, Jeeyun and Leong, Aaron and Shah, Kaanan and Park, Kyu Hyung and Guo, Xiuqing and Ipp, Eli and Taylor, Kent D and Adler, Sharon G and Sedor, John R and Freedman, Barry I and Family Investigation of Nephropathy and Diabetes-Eye Research Group, DCCT/EDIC Research Group and Lee, I-Te and Sheu, Wayne H-H and Kubo, Michiaki and Takahashi, Atsushi and Hadjadj, Samy and Marre, Michel and Tregouet, David-Alexandre and McKean-Cowdin, Roberta and Varma, Rohit and McCarthy, Mark I and Groop, Leif and Ahlqvist, Emma and Lyssenko, Valeriya and Agardh, Elisabet and Morris, Andrew and Doney, Alex S F and Colhoun, Helen M and Toppila, Iiro and Sandholm, Niina and Groop, Per-Henrik and Maeda, Shiro and Hanis, Craig L and Penman, Alan and Chen, Ching J and Hancock, Heather and Mitchell, Paul and Craig, Jamie E and Chew, Emily Y and Paterson, Andrew D and Grassi, Michael A and Palmer, Colin and Bowden, Donald W and Yaspan, Brian L and Siscovick, David and Cotch, Mary Frances and Wang, Jie Jin and Burdon, Kathryn P and Wong, Tien Y and Klein, Barbara E K and Klein, Ronald and Rotter, Jerome I and Iyengar, Sudha K and Price, Alkes L and Sobrin, Lucia}
}
@article {1439859,
	title = {Evolving Images for Visual Neurons Using a Deep Generative Network Reveals Coding Principles and Neuronal Preferences},
	journal = {Cell},
	volume = {177},
	number = {4},
	year = {2019},
	month = {2019 May 02},
	pages = {999-1009.e10},
	abstract = {What specific features should visual neurons encode, given the infinity of real-world images and the limited number of neurons available to represent them? We investigated neuronal selectivity in monkey inferotemporal cortex via the vast hypothesis space of a generative deep neural network, avoiding assumptions about features or semantic categories. A genetic algorithm searched this space for stimuli that maximized neuronal firing. This led to the evolution of rich synthetic images of objects with complex combinations of shapes, colors, and textures, sometimes resembling animals or familiar people, other times revealing novel patterns that did not map to any clear\&nbsp;semantic category. These results expand our conception of the dictionary of features encoded in the cortex, and the approach can potentially reveal the internal representations of any system whose input can be captured by a generative model.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2019.04.005},
	author = {Ponce, Carlos R and Xiao, Will and Schade, Peter F and Hartmann, Till S and Kreiman, Gabriel and Livingstone, Margaret S}
}
@article {1632292,
	title = {Supraspinal Mechanisms Underlying Ocular Pain},
	journal = {Front Med (Lausanne)},
	volume = {8},
	year = {2021},
	month = {2021},
	pages = {768649},
	abstract = {Supraspinal mechanisms of pain are increasingly understood to underlie neuropathic ocular conditions previously thought to be exclusively peripheral in nature. Isolating individual causes of centralized chronic conditions and differentiating them is critical to understanding the mechanisms underlying neuropathic eye pain and ultimately its treatment. Though few functional imaging studies have focused on the eye as an end-organ for the transduction of noxious stimuli, the brain networks related to pain processing have been extensively studied with functional neuroimaging over the past 20 years. This article will review the supraspinal mechanisms that underlie pain as they relate to the eye.},
	issn = {2296-858X},
	doi = {10.3389/fmed.2021.768649},
	author = {Pondelis, Nicholas J and Moulton, Eric A}
}
@article {1664954,
	title = {A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates},
	journal = {EBioMedicine},
	volume = {88},
	year = {2023},
	month = {2023 Feb},
	pages = {104439},
	abstract = {BACKGROUND: Worldwide, Escherichia coli is the leading cause of neonatal Gram-negative bacterial meningitis, but full understanding of the pathogenesis of this disease is not yet achieved. Moreover, to date, no vaccine is available against bacterial neonatal meningitis. METHODS: Here, we used Transposon Sequencing of saturated banks of mutants (TnSeq) to evaluate E.\&nbsp;coli K1 genetic fitness in murine neonatal meningitis. We identified E.\&nbsp;coli K1 genes encoding for factors important for systemic dissemination and brain infection, and focused on products with a likely outer-membrane or extra-cellular localization, as these are potential vaccine candidates. We used in\&nbsp;vitro and in\&nbsp;vivo models to study the efficacy of active and passive immunization. RESULTS: We selected for further study the conserved surface polysaccharide Poly-β-(1-6)-N-Acetyl Glucosamine (PNAG), as a strong candidate for vaccine development. We found that PNAG was a virulence factor in our animal model. We showed that both passive and active immunization successfully prevented and/or treated meningitis caused by E.\&nbsp;coli K1 in neonatal mice. We found an excellent opsonophagocytic killing activity of the antibodies to PNAG and in\&nbsp;vitro these antibodies were also able to decrease binding, invasion and crossing of E.\&nbsp;coli K1 through two blood brain barrier cell lines. Finally, to reinforce the potential of PNAG as a vaccine candidate in bacterial neonatal meningitis, we demonstrated that Group B Streptococcus, the main cause of neonatal meningitis in developed countries, also produced PNAG and that antibodies to PNAG could protect in\&nbsp;vitro and in\&nbsp;vivo against this major neonatal pathogen. INTERPRETATION: Altogether, these results indicate the utility of a high-throughput DNA sequencing method to identify potential immunotherapy targets for a pathogen, including in this study a potential broad-spectrum target for prevention of neonatal bacterial infections. FUNDINGS: ANR Seq-N-Vaq, Charles Hood Foundation, Hearst Foundation, and Groupe Pasteur Mutualit{\'e}.},
	keywords = {Animals, Antibodies, Bacterial, Bacteria, Escherichia coli, High-Throughput Nucleotide Sequencing, Immunotherapy, Meningitis, Bacterial, Mice},
	issn = {2352-3964},
	doi = {10.1016/j.ebiom.2023.104439},
	author = {Pons, St{\'e}phanie and Frapy, Eric and Sereme, Youssouf and Gaultier, Charlotte and Lebreton, Fran{\c c}ois and Kropec, Andrea and Danilchanka, Olga and Schlemmer, Laura and Schrimpf, C{\'e}cile and Allain, Margaux and Angoulvant, Fran{\c c}ois and Lecuyer, Herv{\'e} and Bonacorsi, St{\'e}phane and Aschard, Hugues and Sokol, Harry and Cywes-Bentley, Colette and Mekalanos, John J and Guillard, Thomas and Pier, Gerald B and Roux, Damien and Skurnik, David}
}
@article {1635619,
	title = {Corneal stromal deposits in connective tissue disease, a case series},
	journal = {Am J Ophthalmol Case Rep},
	volume = {25},
	year = {2022},
	month = {2022 Mar},
	pages = {101264},
	abstract = {Purpose: We report two cases of refractile, peripheral, corneal stromal deposition in two patients with arterial tortuosity syndrome (ATS) and Ehlers-Danlos syndrome (EDS), two closely related connective tissue diseases (CTDs). Observations: Patient 1: A 21-year-old man with history of ATS and keratoectasia presented with bilateral peripheral corneal neovascularization with numerous whitish brown, refractile, deep stromal opacities that were circumferential along the inferotemporal cornea. After 3 years of follow-up, the corneal deposits did not progress, but the ectasia did, with significant bilateral corneal steepening and thinning for which the patient was recommended to undergo repeat corneal collagen cross linking. Patient 2: A 26-year-old man with presumed diagnosis of EDS presented with numerous whitish brown, refractile, deep stromal opacities that were circumferential along the temporal cornea in the right eye, and superiorly in the left eye. The left eye had a pseudopterygium involving 50\% of the cornea. After 2 years of follow-up, the corneal opacities did not progress; however, the patient underwent primary excision of the pseudopterygium and subsequently had conjunctivalization of the entire cornea. The lesions in both cases resembled those seen in Terrien{\textquoteright}s marginal degeneration. Conclusions and importance: Peripheral corneal stromal deposits have never been reported before in EDS or ATS or other connective tissue diseases. This case series may prompt further inquiry and characterization of these findings in patients with CTDs.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101264},
	author = {Ponsetto, Momoko K and Elhusseiny, Abdelrahman M and Kwan, James and Saeed, Hajirah N}
}
@article {1363185,
	title = {Reactive retinal astrocytic tumors (so-called vasoproliferative tumors): histopathologic, immunohistochemical, and genetic studies of four cases},
	journal = {Am J Ophthalmol},
	volume = {155},
	number = {3},
	year = {2013},
	month = {2013 Mar},
	pages = {593-608.e1},
	abstract = {PURPOSE: To evaluate the cellular nature of and diagnostic terminology used in connection with acquired retinal "vasoproliferative tumors."

DESIGN: Retrospective clinicopathologic study.

METHODS: Clinical records and microscopic slides of 4 enucleated globes were reviewed. Special stains and immunohistochemical probes for CD31, CD34, p53, glial fibrillary acidic protein (GFAP), CD163, and Ki67 (cell replication) were employed; ultrastructural and fluorescence in situ hybridization (FISH) analyses were performed.

RESULTS: Tumors were located inferotemporally in middle-aged patients. They were uniformly composed of compacted elongated, GFAP-positive spindle cells (due to intermediate filaments identified ultrastructurally) with a Ki67 index of less than 1\%. Rosenthal fibers and eosinophilic granular bodies were observed. Hyalinized periodic acid-Schiff-positive vessels were widely separated. CD31 and CD34 revealed a sparse microvasculature. Tumor-associated exudate spread predominantly subretinally. The retinal pigment epithelium had undergone extensive placoid fibrous metaplasia with focal ossification. P53 upregulation, BRAF-KIAA gene rearrangement, and IDH1R132H mutation typically associated with low-grade astrocytic neoplasms were absent.

CONCLUSIONS: Retinal "vasoproliferative" tumors have been mischaracterized, because they actually display a paucity of microvessels. Proliferating fibrous astrocytes with a very low proliferation index predominate, without immunohistochemical or genetic evidence favoring a neoplasm. Subretinal exudate appeared capable of provoking widespread fibrous metaplasia of the pigment epithelium that was mainly responsible for secondary retinal damage. The term "reactive retinal astrocytic tumor" is proposed as more appropriate for this entity. In carefully selected progressive lesions, consideration should be given to earlier surgical intervention before extensive subretinal exudate accumulates and pigment epithelial proliferation with fibrous metaplasia ensues.},
	keywords = {Adult, Aged, Astrocytes, Astrocytoma, Biomarkers, Tumor, Eye Enucleation, Female, Gene Rearrangement, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Isocitrate Dehydrogenase, Male, Neoplasm Proteins, Oncogene Proteins, Fusion, Polymerase Chain Reaction, Retinal Neoplasms, Retrospective Studies, Terminology as Topic},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2012.09.002},
	author = {Poole Perry, Lynn J and Jakobiec, Frederick A and Zakka, Fouad R and Reichel, Elias and Herwig, Martina C and Perry, Arie and Brat, Daniel J and Grossniklaus, Hans E}
}
@article {1195236,
	title = {The ISNT Rule: How Often Does It Apply to Disc Photographs and Retinal Nerve Fiber Layer Measurements in the Normal Population?},
	journal = {Am J Ophthalmol},
	volume = {184},
	year = {2017},
	month = {2017 Dec},
	pages = {19-27},
	abstract = {PURPOSE: To determine what percentage of normal eyes follow the ISNT rule, and whether ISNT rule variants may be more generalizable to the normal population. DESIGN: Cross-sectional study. METHODS: Setting: Institutional setting. STUDY POPULATION: Total of 110 normal subjects. OBSERVATION PROCEDURES: Neuroretinal rim assessments from disc photographs and retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography. MAIN OUTCOME MEASURES: The percentages of subjects that obeyed the ISNT rule and its variants. RESULTS: The ISNT rule is only valid for 37.0\% of disc photograph rim assessments and 43.8\% of RNFL measurements. Deviation of the nasal sector from the expected ISNT pattern was a major cause for the ISNT rule not being obeyed for both rim and RNFL assessments. Specifically, 10.9\% of subjects had wider nasal rims than the inferior rims, 29.4\% had wider nasal rims than the superior rims, 14.7\% had narrower nasal rims than the temporal rims, and 42.9\% had thinner nasal RNFLs compared to the temporal quadrant. Exclusion of the nasal quadrant from the ISNT rule significantly increased the validity of ISNT variant rules, with 70.9\% and 76.4\% of disc photographs following the IST rule and the IS rule, respectively. Similarly, for RNFL thickness, 70.9\% and 71.8\% of patients followed the IST and IS rule, respectively. CONCLUSIONS: The ISNT rule is only valid for about a third of disc photographs and less than half of RNFL measurements in normal patients. ISNT rule variants, such as the IST and IS rule, may be considered, as they are valid in more than 70\% of patients.},
	keywords = {Cross-Sectional Studies, Female, Healthy Volunteers, Humans, Male, Middle Aged, Nerve Fibers, Optic Disk, Photography, Prospective Studies, Retinal Ganglion Cells, Tomography, Optical Coherence},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.09.018},
	author = {Poon, Linda Yi-Chieh and Sol{\'a}-Del Valle, David and Turalba, Angela V and Falkenstein, Iryna A and Horsley, Michael and Kim, Julie H and Song, Brian J and Takusagawa, Hana L and Wang, Kaidi and Chen, Teresa C}
}
@article {988006,
	title = {Endoscopic Cyclophotocoagulation for the Treatment of Glaucoma in Boston Keratoprosthesis Type II Patient},
	journal = {J Glaucoma},
	volume = {26},
	number = {4},
	year = {2017},
	month = {2017 Apr},
	pages = {e146-e149},
	abstract = {We describe the surgical technique of endoscopic cyclophotocoagulation in a Boston keratoprosthesis type II patient. This patient with ocular cicatricial pemphigoid had pars plana endoscopic cyclophotocoagula through wounds created in the eyelids.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000626},
	author = {Poon, Linda Yi-Chieh and Chodosh, James and Vavvas, Demetrios G and Dohlman, Claes H and Chen, Teresa C}
}
@article {1498261,
	title = {Evaluation of meridional scans for angle closure assessment with anterior segment swept-source optical coherence tomography},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {131-134},
	abstract = {BACKGROUND/AIMS: As swept-source optical coherence tomography (SS-OCT) simultaneously obtains 128 meridional scans, it is important to identify which scans are playing the main role in classifying gonioscopic angle closure to simplify the analysis. We aimed to evaluate the diagnostic performance of every meridional scan in its ability to detect gonioscopic angle closure. METHODS: Observational study with 2027 phakic subjects consecutively recruited from a community polyclinic. Gonioscopy and SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in >=180{\textdegree} of the angle, while SS-OCT was defined as iridotrabecular contact anterior to the scleral spur. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic performance of each single scan, the sequential anticlockwise cumulative effect of those single scans and different combinations of them. RESULTS: The AUCs of each scan ranged from 0.73 to 0.82. The single scan at 80{\textdegree}-260{\textdegree} had the highest AUC (0.82, 95\% CI 0.79 to 0.84) and performed significantly better than most of the temporonasal scans (from 0{\textdegree} to 52{\textdegree} and from 153{\textdegree} to 179{\textdegree}). The superoinferior scans achieved higher AUCs compared with the temporonasal ones. When assessing the cumulative effect of adding individual scans consecutively, the peak AUC (0.80) was obtained when considering the superoinferior scans closer to 80{\textdegree}-85{\textdegree}, but no further positive cumulative effect was seen when adding the rest of the temporonasal scans of the circumference. CONCLUSIONS: In conclusion, the single SS-OCT scan at 80{\textdegree}-260{\textdegree} had the highest diagnostic performance. Our study suggests that the 360{\textdegree} evaluation may not translate to better clinical utility for detection of gonioscopic angle closure.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-315461},
	author = {Porporato, Natalia and Baskaran, Mani and Perera, Shamira and Tun, Tin A and Sultana, Rehena and Tan, Marcus and Quah, Joanne HuiMin and Allen, John C and Friedman, David and Cheng, Ching Yu and Aung, Tin}
}
@article {1466921,
	title = {Understanding diagnostic disagreement in angle closure assessment between anterior segment optical coherence tomography and gonioscopy},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {795-799},
	abstract = {BACKGROUND/AIMS: Although being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy. METHODS: Cross-sectional study. A total of 2027 phakic subjects aged >=50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of >=35\%, >=50\% and >=75\% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT. RESULTS: Two hundred and seventy-two (14.7\%) resulted in overcall results (false positives) when >=50\% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, p\&lt;0.001) and deeper (anterior chamber depth (ACD), 2.4 vs 2.2 mm, p\&lt;0.001) anterior chambers than eyes assessed by both methods as closed (true positives). Deeper ACD (OR 9.31) and lower lens vault (LV) (OR 0.04) were significantly associated with a false positive diagnosis in the multivariate analysis. Most of these cases had short (52.6\%) or irregular (39\%) ITC in SS-OCT images. CONCLUSIONS: We found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-314672},
	author = {Porporato, Natalia and Baskaran, Mani and Tun, Tin A and Sultana, Rehena and Tan, Marcus and Quah, Joanne HuiMin and Allen, John C and Perera, Shamira and Friedman, David S and Cheng, Ching Yu and Aung, Tin}
}
@article {1664974,
	title = {Corneal nerve regeneration is affected by scar location in herpes simplex keratitis: A longitudinal in vivo confocal microscopy study},
	journal = {Ocul Surf},
	year = {2023},
	month = {2023 Jan 13},
	abstract = {PURPOSE: To assess the effect of corneal scarring location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. METHODS: Prospective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation was analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM. RESULTS: In the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 {\textpm} 1.97mm/mm2, p \&lt; 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of peripheral scar (PS) group (all p \&gt; 0.05), and significant nerve regeneration was observed in central corneas (16.39 {\textpm} 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral cornea of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p \&gt; 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p \&lt; 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was \&lt;4 cm in 4 (30.8\%) and 7 (53.8\%) patients in the central and peripheral corneas at baseline, and in 5 (38.5\%) and 2 subjects (15.4\%) at follow-up, whereas in the PS group only 1 patient (10\%) showed a corneal sensation \&lt; 4cm in the central cornea at baseline, and only 1 (10.0\%), 3 (30.0\%) and 1 (10.0\%) patients at follow-up in the central, affected and opposite area of the cornea, respectively. CONCLUSION: The location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, they show a more severe reduction in corneal sensation in the central and peripheral cornea that persist at follow-up, and they have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2023.01.003},
	author = {Posarelli, Matteo and Chirapapaisan, Chareenun and Muller, Rodrigo and Abbouda, Alessandro and Pondelis, Nicholas and Cruzat, Andrea and Cavalcanti, Bernardo M and Cox, Stephanie M and Jamali, Arsia and Pavan-Langston, Deborah and Hamrah, Pedram}
}
@article {341726,
	title = {Quantitative profiling of peptides from RNAs classified as noncoding.},
	journal = {Nat Commun},
	volume = {5},
	year = {2014},
	month = {2014},
	pages = {5429},
	abstract = {Only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into proteins, and it is generally assumed that a large portion of transcribed sequences--including introns and several classes of noncoding RNAs (ncRNAs)--do not give rise to peptide products. A systematic examination of translation and physiological regulation of ncRNAs has not been conducted. Here we use computational methods to identify the products of non-canonical translation in mouse neurons by analysing unannotated transcripts in combination with proteomic data. This study supports the existence of non-canonical translation products from both intragenic and extragenic genomic regions, including peptides derived from antisense transcripts and introns. Moreover, the studied novel translation products exhibit temporal regulation similar to that of proteins known to be involved in neuronal activity processes. These observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential.},
	issn = {2041-1723},
	doi = {10.1038/ncomms6429},
	author = {Prabakaran, Sudhakaran and Hemberg, Martin and Chauhan, Ruchi and Winter, Dominic and Tweedie-Cullen, Ry Y and Dittrich, Christian and Hong, Elizabeth and Gunawardena, Jeremy and Steen, Hanno and Kreiman, Gabriel and Steen, Judith A}
}
@article {1490440,
	title = {Mouse retinal cell behaviour in space and time using light sheet fluorescence microscopy},
	journal = {Elife},
	volume = {9},
	year = {2020},
	month = {2020 Feb 19},
	abstract = {As the general population ages, more people are affected by eye diseases, such as retinopathies. It is therefore critical to improve imaging of eye disease mouse models. Here, we demonstrate that 1) rapid, quantitative 3D and 4D (time lapse) imaging of cellular and subcellular processes in the mouse eye is feasible, with and without tissue clearing, using light-sheet fluorescent microscopy (LSFM); 2) flat-mounting retinas for confocal microscopy significantly distorts tissue morphology, confirmed by quantitative correlative LSFM-Confocal imaging of vessels; 3) LSFM readily reveals new features of even well-studied eye disease mouse models, such as the oxygen-induced retinopathy (OIR) model, including a previously unappreciated {\textquoteright}knotted{\textquoteright} morphology to pathological vascular tufts, abnormal cell motility and altered filopodia dynamics when live-imaged. We conclude that quantitative 3D/4D LSFM imaging and analysis has the potential to advance our understanding of the eye, in particular pathological, neuro-vascular, degenerative processes.},
	issn = {2050-084X},
	doi = {10.7554/eLife.49779},
	author = {Prahst, Claudia and Ashrafzadeh, Parham and Mead, Thomas and Figueiredo, Ana and Chang, Karen and Douglas Richardson and Venkaraman, Lakshmi and Richards, Mark and Russo, Ana Martins and Harrington, Kyle and Ouarn{\'e}, Marie and Pena, Andreia and Chen, Dong Feng and Claesson-Welsh, Lena and Cho, Kin-Sang and Franco, Claudio A and Bentley, Katie}
}
@article {1619415,
	title = {Photographic assessment of eyelid position using a simple measurement tool paired with cell phone photography in a pediatric population},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Oct 14},
	abstract = {PURPOSE: This proof-of-concept study evaluates the ability to assess eyelid measurements and the reproducibility of eyelid measurements using a simple measurement tool paired with digital cell phone photography in children. METHODS: Seventy consecutive patients and their siblings, 2-19\&nbsp;years of age, were prospectively enrolled. Participants underwent clinical examination and cell phone photography with a simple measurement tool. An ophthalmologist and nonophthalmologist assessed photographs for interpalpebral fissure distance (IPFD), margin reflex distance-1 (MRD1), and levator function (LF). Clinical examinations and photographs were repeated on the same day in a random sample (n\&nbsp;=\&nbsp;20). The agreement of grading photographs compared to clinical examination was assessed using Bland-Altman plots. Intra-grader repeatability of the clinical examination, repeatability of photographic technique, and interobserver reproducibility of photographic assessment was evaluated with intraclass correlation coefficients (ICC). RESULTS: Of photographs acquired, both graders considered quality good/fair in 100\% to assess IPFD and MRD1, and 70\% to assess LF. The mean difference (limits of agreement) in mm between clinical examination and photographic assessment was 1.1 (-1.5 to 3.8) for IPFD, 0.7 (-1.8 to 3.1) for MRD1, and 1.1 (-3.5 to 5.7) for LF. Intraobserver repeatability on clinical examination was excellent for IPFD (ICC\&nbsp;=\&nbsp;0.81), MRD1 (ICC\&nbsp;=\&nbsp;0.88), and LF (ICC\&nbsp;=\&nbsp;0.94). Repeatability of photographic technique was fair for IPFD (ICC\&nbsp;=\&nbsp;0.44) and good for MRD1 (ICC\&nbsp;=\&nbsp;0.74) and LF (ICC\&nbsp;=\&nbsp;0.77). Interobserver photographic assessment repeatability was excellent for IPFD (ICC\&nbsp;=\&nbsp;0.94), MRD1 (ICC\&nbsp;=\&nbsp;0.96), and LF (ICC\&nbsp;=\&nbsp;0.92). CONCLUSIONS: Photographic assessment of eyelid measurements in children is possible, highly reproducible between graders, and enables documentation for future comparison.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2021.05.020},
	author = {Prakalapakorn, S Grace and Weinert, Marguerite C and Stinnett, Sandra S}
}
@article {1698226,
	title = {Rational design of peptide-based implants for corneal bioengineering},
	journal = {Curr Opin Biotechnol},
	volume = {81},
	year = {2023},
	month = {2023 Jun},
	pages = {102947},
	abstract = {Regeneration of damaged cornea can save vision for millions of patients. Most of these patients are waiting for transplantation of a donor cornea or suitable substitute to restore vision. Although donor cornea transplantation is the most clinically accepted treatment, shortage of donor cornea results in almost 69 out of every 70 patients untreated with the waiting list for transplantation drastically increasing every year according to a prepandemic estimation. Therefore, corneal replacements are coming up as a cutting-edge alternative strategy. In view of the peptides, especially collagen-like peptides and peptide amphiphiles with bioactive functional motifs demonstrate promising avenue for the corneal tissue engineering and promoting regeneration, by their hierarchical self-assembling propensity to acquire desired nano- to macroscale 3D architecture. Here, we analyze rational peptide designing, self-assembly, and strategies of peptide/peptide-based nanoscale building blocks to create the extracellular matrix mimetic implants for functional regeneration of the cornea.},
	keywords = {Biomedical Engineering, Cornea, Humans, Peptides, Regeneration, Tissue Engineering},
	issn = {1879-0429},
	doi = {10.1016/j.copbio.2023.102947},
	author = {Pramanik, Bapan and Islam, Mohammad M and Patra, Hirak K}
}
@article {1478347,
	title = {Neuro-Ophthalmology},
	journal = {Semin Neurol},
	volume = {39},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {671-672},
	issn = {1098-9021},
	doi = {10.1055/s-0039-3401004},
	author = {Prasad, Sashank}
}
@article {1360120,
	title = {Case 37-2018: A 23-Year-Old Woman with Vision Loss},
	journal = {N Engl J Med},
	volume = {379},
	number = {22},
	year = {2018},
	month = {2018 Nov 29},
	pages = {2152-2159},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc1807501},
	author = {Prasad, Sashank and Young, Lucy H and Bouffard, Marc and Rajiv Gupta}
}
@article {1709721,
	title = {Innate Immune Cytokine Levels in Eyes With Late Endothelial Keratoplasty Failure},
	journal = {Cornea},
	year = {2023},
	month = {2023 Jun 16},
	abstract = {PURPOSE: The aim of this study was to compare aqueous humor cytokine levels in eyes with an initial endothelial keratoplasty (EK) that cleared and later decompensated versus control eyes. METHODS: In this prospective case-control study, aqueous humor samples were collected under sterile conditions at the start of planned cataract or EK surgery in normal controls (n = 10), Fuchs dystrophy controls with no previous surgery (n = 10) or previous cataract surgery only (n = 10), eyes with Descemet membrane EK (DMEK) endothelial decompensation (n = 5), and eyes with Descemet stripping EK (DSEK) endothelial decompensation (n = 9). Cytokine levels were quantified with the LUNARIS Human 11-Plex Cytokine Kit and compared using the Kruskal-Wallis nonparametric test and post hoc Wilcoxon pairwise 2-sided multiple comparison test. RESULTS: Levels of granulocyte-macrophage colony-stimulating factor, interferon gamma, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, and tumor necrosis factorα did not differ significantly between groups. However, IL-6 was significantly increased in DSEK regraft eyes versus controls without previous ocular surgery. IL-8 was significantly increased in eyes with previous cataract or EK surgery versus eyes without previous surgery, and IL-8 was significantly increased in DSEK regraft eyes versus eyes with previous cataract surgery. CONCLUSIONS: The levels of innate immune cytokines IL-6 and IL-8 were elevated in the aqueous humor of eyes with failed DSEK, but not with failed DMEK. The differences between DSEK and DMEK may be related to the lower inherent immunogenicity of DMEK grafts and/or the more advanced stage of some of the DSEK graft failures at the time of diagnosis and treatment.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003331},
	author = {Price, Marianne O and Marzidovsek, Zala Luznik and Price, Francis W and Dana, Reza}
}
@article {1532357,
	title = {Enterococci from Wild Magellanic Penguins (Spheniscus magellanicus) as an Indicator of Marine Ecosystem Health and Human Impact},
	journal = {Appl Environ Microbiol},
	volume = {86},
	number = {19},
	year = {2020},
	month = {2020 Sep 17},
	abstract = {Enterococci are commensals that proliferated as animals crawled ashore hundreds of millions of years ago. They are also leading causes of multidrug-resistant hospital-acquired infections. While most studies are driven by clinical interest, comparatively little is known about enterococci in the wild or the effect of human activity on them. Pharmaceutical pollution and runoff from other human activities are encroaching widely into natural habitats. To assess their reach into remote habitats, we investigated the identity, genetic relatedness, and presence of specific traits among 172 enterococcal isolates from wild Magellanic penguins. Four enterococcal species, 18 lineage groups, and different colonization patterns were identified. One lineage, sequence type 475 (ST475), was isolated from three different penguins, making it of special interest. Its genome was compared to those of other sequence types (ST116 and ST242) recovered from Magellanic penguins, as well as to an existing phylogeny of isolated from diverse origins over the past 100 years. No penguin-derived strains were closely related to dominant clinical lineages. Most possessed intact CRISPR defenses, few mobile elements, and antibiotic resistances limited to those intrinsic to the species and lacked pathogenic features conveyed by mobile elements. Interestingly, plasmids were identified in penguin isolates that also had been reported for other marine mammals. Enterococci isolated from penguins showed limited anthropogenic impact, indicating that they are likely representative of those naturally circulating in the ecosystem inhabited by the penguins. These findings establish an important baseline for detecting the encroachment of human activity into remote planetary environments. Enterococci are host-associated microbes that have an unusually broad range, from the built hospital environment to the guts of insects and other animals in remote locations. Despite their occurrence in the guts of animals for hundreds of millions of years, we know little about the properties that confer this range or how anthropogenic activities may be introducing new selective forces. Magellanic penguins live at the periphery of human habitation. It was of interest to examine enterococci from these animals for the presence of antibiotic resistance and other markers reflective of anthropogenic selection. Diverse enterococcal lineages found discount the existence of a single well-adapted intrinsic penguin-specific species. Instead, they appear to be influenced by a carnivorous lifestyle and enterococci present in the coastal sea life consumed. These results indicate that currently, the penguin habitat remains relatively free of pollutants that select for adaptation to human-derived stressors.},
	issn = {1098-5336},
	doi = {10.1128/AEM.01662-20},
	author = {Prichula, Janira and Van Tyne, Daria and Schwartzman, Julia and Sant{\textquoteright}Anna, Fernando Hayashi and Pereira, Rebeca Inhoque and da Cunha, Gabriela Rosa and Tavares, Maur{\'\i}cio and Lebreton, Fran{\c c}ois and Frazzon, Jeverson and d{\textquoteright}Azevedo, Pedro Alves and Seixas, Adriana and Frazzon, Ana Paula Guedes and Gilmore, Michael S}
}
@article {705116,
	title = {Blood biomarkers in a mouse model of CADASIL.},
	journal = {Brain Res},
	volume = {1644},
	year = {2016},
	month = {2016 Aug 1},
	pages = {118-26},
	abstract = {Mutations in NOTCH 3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a neurological disorder characterized by stroke, and vascular cognitive impairment and dementia. Loss of vascular smooth muscle cells (VSMC) and accumulation of granular osmiophilic material (GOM) deposits are hallmarks of CADASIL. There are no therapies for CADASIL and experimental endpoints to examine the preclinical efficacy of potential drugs are lacking. This study aims to use a mouse carrying the C455R mutation in Notch 3 to identify biomarkers associated with CADASIL. Mass spectrometry and antibody arrays were used to explore the aorta and blood proteomes of CADASIL mice, ELISA assays were utilized for biomarker validation, a ligand-dependent assay was applied to examine the relationship between Notch signaling and biomarker expression, and retinal histology was performed for quantification of VSMC loss in arteries. Two-hundred day-old mice with the C455R CADASIL mutation in Notch 3 mice display robust VSMC loss in retinal arteries and had increased plasma levels of collagen18α1/endostatin (col18α1) and high-temperature requirement A serine peptidase 1 (HTRA1) and reduced levels of Notch 3 extracellular domain (N3ECD), compared to control wild type mice. Measurements of plasma endostatin, HTRA1 and N3ECD, along with VSMC quantification in retinal arteries, may serve as surrogate endpoints for assessing efficacy in preclinical therapeutic studies of CADASIL using mice.},
	issn = {1872-6240},
	doi = {10.1016/j.brainres.2016.05.008},
	author = {Primo, Vincent and Graham, Mark and Bigger-Allen, Alexander A and Chick, Joel M and Ospina, Carolina and Quiroz, Yakeel T and Manent, Jan and Gygi, Steven P and Lopera, Francisco and D{\textquoteright}Amore, Patricia A and Arboleda-Velasquez, Joseph F}
}
@article {1589764,
	title = {Area under the dark adaptation curve as a reliable alternate measure of dark adaptation response},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {10},
	year = {2022},
	month = {2022 10},
	pages = {1450-1456},
	abstract = {PURPOSE: Quantification of dark adaptation (DA) response using the conventional rod intercept time (RIT) requires very long testing time and may not be measurable in the presence of impairments due to diseases such as age-related macular degeneration (AMD). The goal of this study was to investigate the advantages of using area under the DA curve (AUDAC) as an alternative to the conventional parameters to quantify DA response. METHODS: Data on 136 eyes (AMD: 98, normal controls: 38) from an ongoing longitudinal study on AMD were used. DA was measured using the AdaptDx 20 min protocol. AUDAC was computed from the raw DA characteristic curve at different time points, including 6.5 min and 20 min (default). The presence of AMD in the given eye was predicted using a logistic regression model within the leave-one-out cross-validation framework, with DA response as the predictor while adjusting for age and gender. The DA response variable was either the AUDAC values computed at 6.5 min (AUDAC6.5) or at 20 min (AUDAC20) cut-off, or the conventional RIT. RESULTS: AUDAC6.5 was strongly correlated with AUDAC20 (β=86, p\&lt;0.001, R2=0.87). The accuracy of predicting the presence of AMD using AUDAC20 was 76\%, compared with 79\% when using RIT, the current gold standard. In addition, when limiting AUDAC calculation to 6.5 min cut-off, the predictive accuracy of AUDAC6.5 was 80\%. CONCLUSIONS: AUDAC can be a valuable measure to quantify the overall DA response and can potentially facilitate shorter testing duration while maintaining diagnostic accuracy.},
	keywords = {Cross-Sectional Studies, Dark Adaptation, Humans, Longitudinal Studies, Macular Degeneration, Visual Acuity},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-318806},
	author = {Pundlik, Shrinivas and Nigalye, Archana and La{\'\i}ns, In{\^e}s and Mendez, Kevin M and Katz, Raviv and Kim, Janice and Kim, Ivana K and Miller, John B and Vavvas, Demetrios and Miller, Joan W and Luo, Gang and Husain, Deeba}
}
@article {1603856,
	title = {Home-Use Evaluation of a Wearable Collision Warning Device for Individuals With Severe Vision Impairments: A Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {9},
	year = {2021},
	month = {2021 Sep 01},
	pages = {998-1005},
	abstract = {Importance: There is scant rigorous evidence about the real-world mobility benefit of electronic mobility aids. Objective: To evaluate the effect of a collision warning device on the number of contacts experienced by blind and visually impaired people in their daily mobility. Design, Setting, and Participants: In this double-masked randomized clinical trial, participants used a collision warning device during their daily mobility over a period of 4 weeks. A volunteer sample of 31 independently mobile individuals with severe visual impairments, including total blindness and peripheral visual field restrictions, who used a long cane or guide dog as their habitual mobility aid completed the study. The study was conducted from January 2018 to December 2019. Interventions: The device automatically detected collision hazards using a chest-mounted video camera. It randomly switched between 2 modes: active mode (intervention condition), where it provided alerts for detected collision threats via 2 vibrotactile wristbands, and silent mode (control condition), where the device still detected collisions but did not provide any warnings to the user. Scene videos along with the collision warning information were recorded by the device. Potential collisions detected by the device were reviewed and scored, including contacts with the hazards, by 2 independent reviewers. Participants and reviewers were masked to the device operation mode. Main Outcomes and Measures: Rate of contacts per 100 hazards per hour, compared between the 2 device modes within each participant. Modified intention-to-treat analysis was used. Results: Of the 31 included participants, 18 (58\%) were male, and the median (range) age was 61 (25-73) years. A total of 19 participants (61\%) had a visual acuity (VA) of light perception or worse, and 28 (90\%) reported a long cane as their habitual mobility aid. The median (interquartile range) number of contacts was lower in the active mode compared with silent mode (9.3 [6.6-14.9] vs 13.8 [6.9-24.3]; difference, 4.5; 95\% CI, 1.5-10.7; P \&lt; .001). Controlling for demographic characteristics, presence of VA better than light perception, and fall history, the rate of contacts significantly reduced in the active mode compared with the silent mode (β = 0.63; 95\% CI, 0.54-0.73; P \&lt; .001). Conclusions and Relevance: In this study involving 31 visually impaired participants, the collision warnings were associated with a reduced rate of contacts with obstacles in daily mobility, indicating the potential of the device to augment habitual mobility aids. Trial Registration: ClinicalTrials.gov Identifier: NCT03057496.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.2624},
	author = {Pundlik, Shrinivas and Baliutaviciute, Vilte and Moharrer, Mojtaba and Bowers, Alex R and Luo, Gang}
}
@article {1761846,
	title = {Impact of Apps as Assistive Devices for Visually Impaired Persons},
	journal = {Annu Rev Vis Sci},
	volume = {9},
	year = {2023},
	month = {2023 Sep 15},
	pages = {111-130},
	abstract = {The pervasiveness of mobile devices and other associated technologies has affected all aspects of our daily lives. People with visual impairments are no exception, as they increasingly tend to rely on mobile apps for assistance with various visual tasks in daily life. Compared to dedicated visual aids, mobile apps offer advantages such as affordability, versatility, portability, and ubiquity. We have surveyed hundreds of mobile apps of potential interest to people with vision impairments, either released as special assistive apps claiming to help in tasks such as text or object recognition (n = 68), digital accessibility (n = 84), navigation (n = 44), and remote sighted service (n = 4), among others, or marketed as general camera magnification apps that can be used for visual assistance (n = 77). While assistive apps as a whole received positive feedback from visually impaired users, as reported in various studies, evaluations of the usability of every app were typically limited to user reviews, which are often not scientifically informative. Rigorous evaluation studies on the effect of vision assistance apps on daily task performance and quality of life are relatively rare. Moreover, evaluation criteria are difficult to establish, given the heterogeneity of the visual tasks and visual needs of the users. In addition to surveying literature on vision assistance apps, this review discusses the feasibility and necessity of conducting scientific research to understand visual needs and methods to evaluate real-world benefits.},
	keywords = {Humans, Mobile Applications, Quality of Life, Self-Help Devices, Visual Perception, Visually Impaired Persons},
	issn = {2374-4650},
	doi = {10.1146/annurev-vision-111022-123837},
	author = {Pundlik, Shrinivas and Shivshanker, Prerana and Luo, Gang}
}
@article {397851,
	title = {Evaluation of a portable collision warning device for patients with peripheral vision loss in an obstacle course.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2015},
	month = {2015 Mar 18},
	abstract = {PURPOSE: A pocket-sized collision warning device equipped with a video camera was developed to predict impending collisions based on time to collision rather than proximity. A study was conducted in a high density obstacle course to evaluate the effect of the device on collision avoidance in people with peripheral field loss (PFL). METHODS: The 41 meter long loop-shaped obstacle course consisted of 46 stationary obstacles from floor to head level, and oncoming pedestrians. Twenty five patients with tunnel vision (n = 13) or hemianopia (n = 12) completed 4 consecutive loops with and without the device, while not using any other habitual mobility aid. Walking direction and device usage order were counterbalanced. Number of collisions and preferred percentage of walking speed (PPWS) were compared within subjects. RESULTS: Collisions were reduced significantly by about 37\% (p \&lt; 0.001) with the device (Floor-level obstacles were excluded because the device was not designed for them). No patient had more collisions when using the device. While the PPWS also reduced with the device from 52\% to 49\% (p = 0.053), this did not account for the lower number of collisions, as the changes in collisions and PPWS were not correlated (p = 0.516). CONCLUSIONS: The device may help patients with a wide range of PFL avoid collisions with high-level obstacles and barely affect their walking speed.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15935},
	author = {Pundlik, Shrinivas J and Tomasi, Matteo and Luo, Gang}
}
@article {1789141,
	title = {Investigation of Population-Based Fall Risk in Eye Diseases},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {2},
	year = {2024},
	month = {2024 Feb 01},
	pages = {106-107},
	keywords = {Disease Susceptibility, Eye Diseases, Humans, Risk Factors},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.6102},
	author = {Pundlik, Shrinivas and Luo, Gang}
}
@article {1789176,
	title = {Evaluation of a mobile app for dark adaptation measurement in individuals with age-related macular degeneration},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Dec 14},
	pages = {22191},
	abstract = {We present clinical evaluation of a mobile app for dark adaptation (DA) measurement in age-related macular degeneration (AMD) patients and in older adults (age \&gt; 50\&nbsp;years) without AMD or other retinal disorders (NV). The outcome measures were the area under dark adaptation curve (AUDAC) and the time for visual sensitivity to recover by 3 log units (TR). Larger AUDAC and TR values indicated worse DA response. The association of AUDAC with AMD was analyzed using linear regression, while time-to-event analysis was used for TR. 32 AMD patients (mean {\textpm} SD; age:72 {\textpm} 6.3\&nbsp;years, VA:0.09 {\textpm} 0.08 logMAR) and 25 NV subjects (mean {\textpm} sd; age:65 {\textpm} 8.7\&nbsp;years, VA:0.049 {\textpm} 0.07 logMAR) were measured with the app. Controlling for age, VA, and cataract severity, the AMD presence was significantly associated with higher AUDAC (β = 0.41, 95\% CI 0.18-0.64, p = 0.001) and with slower sensitivity recovery (β = 0.32, 95\% CI 0.15-0.69, p = 0.004). DA measurements with the app were highly correlated with those obtained with AdaptDx-an established clinical device (n = 18, ρ = 0.87, p \&lt; 0.001). AMD classification accuracy using the app was 72\%, which was comparable to the 71\% accuracy of AdaptDx. Our findings indicate that the mobile app provided reliable and clinically meaningful DA measurements that were strongly correlated with the current standard of care in AMD.},
	keywords = {Aged, Cross-Sectional Studies, Dark Adaptation, Humans, Macular Degeneration, Middle Aged, Mobile Applications, Visual Acuity},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-48898-5},
	author = {Pundlik, Shrinivas and Shivshanker, Prerana and Nigalye, Archana and Luo, Gang and Husain, Deeba}
}
@article {1782366,
	title = {Gaze Scanning at Street Crossings by Pedestrians With Homonymous Hemianopia With and Without Hemispatial Neglect},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {64},
	number = {14},
	year = {2023},
	month = {2023 Nov 01},
	pages = {26},
	abstract = {PURPOSE: To investigate compensatory gaze-scanning behaviors during street crossings by pedestrians with homonymous hemianopia (HH) and hemispatial neglect (HSN). METHODS: Pedestrians with right homonymous hemianopia (RHH) and left homonymous hemianopia without (LHH) and with left spatial-neglect (LHSN) walked on city streets wearing a gaze-tracking system that also captured scene videos. Street-crossing instances were manually annotated, and horizontal gaze scan of magnitude >=20{\textdegree} and scanning rates were compared within-subject, between the side of the hemifield loss (BlindSide) and the other side (SeeingSide). Proportion of instances with scans to both the left and the right side at nonsignalized crossings (indicative of safe scanning behavior) were compared among the three subject groups. RESULTS: Data from 19 participants (6 LHH, 7 RHH, and 6 with mild [4] or moderate [2] LHSN), consisting of 521 street-crossing instances of a total duration of 201 minutes and 5375 gaze scans, were analyzed. The overall gaze magnitude (mean [95\% confidence interval (CI)]) was significantly larger toward the BlindSide (40.4{\textdegree} [39.1{\textdegree}-41.9{\textdegree}]) than the SeeingSide (36{\textdegree} [34.8{\textdegree}-37.3{\textdegree}]; P \&lt; 0.001). The scanning rate (mean [95\% CI] scans/min) toward the BlindSide (14 [12.5-15.6]) was significantly higher than the SeeingSide (11.5 [10.3{\textdegree}-12.9{\textdegree}]; P \&lt; 0.001). The scanning rate in the LHSN group (10.7 [8.9-12.8]) was significantly lower than the LHH group (14 [11.6-17.0]; P = 0.045). The proportion of nonsignalized crossings with scans to both sides was significantly lower in LHSN (58\%; P = 0.039) and RHH (51\%; P = 0.003) than LHH (75\%) participants. CONCLUSIONS: All groups demonstrated compensatory scanning, making more gaze scans with larger magnitudes to the blind side. Mild to moderate LHSN adversely impacted the scanning rate.},
	keywords = {Hemianopsia, Humans, Pedestrians, Perceptual Disorders, Visual Fields},
	issn = {1552-5783},
	doi = {10.1167/iovs.64.14.26},
	author = {Pundlik, Shrinivas and Tomasi, Matteo and Houston, Kevin E and Kumar, Ayush and Shivshanker, Prerana and Bowers, Alex R and Peli, Eli and Luo, Gang}
}
@article {1748371,
	title = {TUBB3 and KIF21A in neurodevelopment and disease},
	journal = {Front Neurosci},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {1226181},
	abstract = {Neuronal migration and axon growth and guidance require precise control of microtubule dynamics and microtubule-based cargo transport. TUBB3 encodes the neuronal-specific β-tubulin isotype III, TUBB3, a component of neuronal microtubules expressed throughout the life of central and peripheral neurons. Human pathogenic TUBB3 missense variants result in altered TUBB3 function and cause errors either in the growth and guidance of cranial and, to a lesser extent, central axons, or in cortical neuronal migration and organization, and rarely in both. Moreover, human pathogenic missense variants in KIF21A, which encodes an anterograde kinesin motor protein that interacts directly with microtubules, alter KIF21A function and cause errors in cranial axon growth and guidance that can phenocopy TUBB3 variants. Here, we review reported TUBB3 and KIF21A variants, resulting phenotypes, and corresponding functional studies of both wildtype and mutant proteins. We summarize the evidence that, in vitro and in mouse models, loss-of-function and missense variants can alter microtubule dynamics and microtubule-kinesin interactions. Lastly, we highlight additional studies that might contribute to our understanding of the relationship between specific tubulin isotypes and specific kinesin motor proteins in health and disease.},
	issn = {1662-4548},
	doi = {10.3389/fnins.2023.1226181},
	author = {Puri, Dharmendra and Barry, Brenda J and Engle, Elizabeth C}
}
@article {1817231,
	title = {Antiviral treatment for acute retinal necrosis: A systematic review and meta-analysis},
	journal = {Surv Ophthalmol},
	volume = {69},
	number = {1},
	year = {2024},
	month = {2024 Jan-Feb},
	pages = {67-84},
	abstract = {Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63\% (95\% CI: 55-71\%) and 35\% (95\% CI: 28-42\%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37\% (95\% CI: 27-47\%), 14\% (95\% CI: 8-21\%), and 43\% (95\% CI: 38-50\%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P\&nbsp;=\&nbsp;0.83).},
	keywords = {Acyclovir, Antiviral Agents, Eye Infections, Viral, Humans, Retinal Detachment, Retinal Necrosis Syndrome, Acute, Retrospective Studies},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2023.09.004},
	author = {Putera, Ikhwanuliman and Ridwan, Asri Salima and Dewi, Metta and Cifuentes-Gonz{\'a}lez, Carlos and Rojas-Carabali, William and Sitompul, Ratna and Edwar, Lukman and Susiyanti, Made and Aziza, Yulia and Pavesio, Carlos and Chee, Soon-Phaik and Mahendradas, Padmamalini and Biswas, Jyotirmay and Kempen, John H and Gupta, Vishali and de-la-Torre, Alejandra and Distia Nora, Rina La and Agrawal, Rupesh}
}
@article {1608580,
	title = {Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {10},
	year = {2021},
	month = {2021 Aug 12},
	pages = {3},
	abstract = {Purpose: Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow-derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits. Methods: Human bone marrow-derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes. Results: The viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1\% {\textpm} 2.1\% and 94.9\% {\textpm} 1.3\%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5\% {\textpm} 12.1\% in epithelial cells co-cultured with MSCs compared with 40.8\% {\textpm} 23.1\% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100\% corneal wound closure compared with 79.9\% {\textpm} 5.5\% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection. Conclusions: Subconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models. Translational Relevance: These results provide preclinical data to support a phase I clinical study.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.10.3},
	author = {Putra, Ilham and Shen, Xiang and Anwar, Khandaker N and Rabiee, Behnam and Samaeekia, Ravand and Almazyad, Enmar and Giri, Pushpanjali and Jabbehdari, Sayena and Hayat, Mohammed R and Elhusseiny, Abdelrahman M and Ghassemi, Mahmood and Mahmud, Nadim and Edward, Deepak P and Joslin, Charlotte E and Rosenblatt, Mark I and Dana, Reza and Eslani, Medi and Hematti, Peiman and Djalilian, Ali R}
}
@article {1363187,
	title = {Corneal Allograft Rejection: Immunopathogenesis to Therapeutics},
	journal = {J Clin Cell Immunol},
	volume = {2013},
	number = {Suppl 9},
	year = {2013},
	month = {2013 Nov 20},
	abstract = {Corneal transplantation is among the most successful solid organ transplants. However, despite low rejection rates of grafts in the {\textquoteright}low-risk{\textquoteright} setting, rejection can be as high as 70\% when grafted into {\textquoteright}high-risk{\textquoteright} recipient beds. Under normal homeostatic conditions, the avascular cornea provides a unique environment that facilitates immune and angiogenic privilege. An imbalance in pro-inflammatory, angiogenic and lymphangiogenic mediators leads to a breakdown in corneal immune privilege with a consequent host response against the donor graft. Recent developments in lamellar and endothelial keratoplasties have reduced the rates of graft rejection even more, while providing improved visual outcomes. The corneal layer against which an immune response is initiated, largely determines reversibility of the acute episode. While epithelial and stromal graft rejection may be treated with topical corticosteroids with higher success, acute endothelial rejection mandates a more aggressive approach to therapy due to the lack of regenerative capacity of this layer. However, current immunosuppressive regimens come with the caveat of ocular and systemic side effects, making prolonged aggressive treatment undesirable. With the advent of biologics, efficacious therapies with a superior side effect profile are on the horizon. In our review we discuss the mediators of ocular immune privilege, the roles of cellular and molecular immune players in graft rejection, with a focus on human leukocyte antigen and antigen presenting cells. Furthermore, we discuss the clinical risk factors for graft rejection and compare rates of rejection in lamellar and endothelial keratoplasties to traditional penetrating keratoplasty. Lastly, we present the current and upcoming measures of therapeutic strategies to manage and treat graft rejection, including an overview of biologics and small molecule therapy.},
	issn = {2155-9899},
	doi = {10.4172/2155-9899.S9-006},
	author = {Qazi, Yureeda and Hamrah, Pedram}
}
@article {836941,
	title = {Validity and Reliability of a Novel Ocular Pain Assessment Survey (OPAS) in Quantifying and Monitoring Corneal and Ocular Surface Pain.},
	journal = {Ophthalmology},
	volume = {123},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {1458-68},
	abstract = {PURPOSE: To validate the Ocular Pain Assessment Survey (OPAS), specifically designed to measure ocular pain and quality of life for use by eye care practitioners and researchers. DESIGN: A single-center cohort study was conducted among patients with and without corneal and ocular surface pain at initial and follow-up visits over a 6-month period. The content of the OPAS was guided by literature review, a body of experts, and incorporating conceptual frameworks from existing pain questionnaires. The Wong-Baker FACES Pain Rating Scale served as the gold standard for measuring the intensity of ocular pain. PARTICIPANTS: A total of 102 patients aged 18 to 80 years completed the OPAS at the initial visit. A total of 21 patients were followed up after treatment. METHODS: Indices of validity and internal consistency (Spearman{\textquoteright}s rank-order, rs, or Pearson{\textquoteright}s correlation coefficients, rp), and coefficient of reliability (Cronbach{\textquoteright}s α) were determined in addition to equivalence testing, exploratory factor analysis (EFA), and diagnostic analysis. MAIN OUTCOME MEASURES: Eye pain intensity was the primary outcome measure, and interference with quality of life (QoL), aggravating factors, associated factors, associated non-eye pain intensity, and self-reported symptomatic relief were the secondary outcome measures. RESULTS: The OPAS had criterion validity at both initial (rs\&nbsp;= 0.71; n\&nbsp;= 102; P \&lt; 0.01) and follow-up visits (rs\&nbsp;= 0.97; n\&nbsp;= 21; P \&lt; 0.01). Equivalence tests yielded OPAS and gold standard equivalence for both the initial and follow-up visits. The EFA supported 6 subscales (eye pain intensity at 24 hours and 2 weeks, non-eye pain intensity, QoL, aggravating factors, and associated factors) confirming multidimensionality. Cronbach{\textquoteright}s α \&gt;0.83 for all subscales established strong internal consistency, which correlated with the gold standard, including 24-hour eye pain intensity and QoL interference scores (rp\&nbsp;= 0.81, 0.64, respectively P \&lt; 0.001). At follow-up, reduction in pain scores was accompanied by improvement in all dimensions of the OPAS. Percentage change in QoL correlated to percentage change in the gold standard (rp\&nbsp;= 0.53; P\&nbsp;\&lt; 0.05). The OPAS was sensitive (94\%), specific (81\%), and accurate (91\%), with a diagnostic odds ratio\&nbsp;\&gt;50. CONCLUSIONS: The OPAS is a valid, reliable, and responsive tool with strong psychometric and diagnostic properties in the multidimensional quantification of corneal and ocular surface pain intensity, and QoL.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.03.006},
	author = {Qazi, Yureeda and Hurwitz, Shelley and Khan, Sarosh and Jurkunas, Ula V and Dana, Reza and Hamrah, Pedram}
}
@article {468966,
	title = {In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study.},
	journal = {Eye (Lond)},
	volume = {29},
	number = {8},
	year = {2015},
	month = {2015 Aug},
	pages = {1099-110},
	abstract = {PurposeThe utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement.MethodsA retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n=3), treatment-responsive MGD patients with improved symptoms (n=3) and asymptomatic healthy normals (n=11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured.ResultsDespite clinical improvement (TBUT: 6.4{\textpm}1.2 s to 10.1{\textpm}2.1 s, P=0.03; MGYLS: 3.5{\textpm}0.8 glands to 7.0{\textpm}1.1 glands, P=0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC=592.6{\textpm}110.1 cells/mm(2); untreated MGD EIC=522.6{\textpm}104.7 cells/mm(2), P=0.69; responsive MGD EIC=194.9{\textpm}119.4 cells/mm(2), P\&lt;0.01; normals EIC=123.7{\textpm}19.2 cells/mm(2), P\&lt; 0.001), but not the cornea (refractory MGD DC=60.9{\textpm}28.3 cells/mm(2); normals DC=25.9{\textpm}6.3 cells/mm(2); P=0.43). EIC did not correlate with TBUT (Rs=-0.26, P=0.33). OSDI scores correlated with both EIC (Rs=0.76, P\&lt;0.001) and TBUT (Rs=-0.69, P\&lt;0.01) but not SIC. Intraglandular immune cells were also seen.ConclusionMGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy.},
	issn = {1476-5454},
	doi = {10.1038/eye.2015.103},
	author = {Qazi, Y and Kheirkhah, A and Blackie, C and Cruzat, A and Trinidad, M and Williams, C. and Korb, D R and Hamrah, P}
}
@article {1363186,
	title = {Gene therapy in corneal transplantation},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {287-300},
	abstract = {Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90\% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection.},
	keywords = {Allografts, Corneal Transplantation, Genetic Therapy, Graft Rejection, Graft Survival, Humans},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825297},
	author = {Qazi, Yureeda and Hamrah, Pedram}
}
@article {341766,
	title = {FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals.},
	journal = {Hum Mol Genet},
	volume = {23},
	number = {25},
	year = {2014},
	month = {2014 Dec 20},
	pages = {6961-72},
	abstract = {FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 {\texttimes} 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 {\texttimes} 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] \%, P = 2.4 {\texttimes} 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] \%, P = 0.004). The associations with protein (P = 7.5 {\texttimes} 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddu411},
	author = {Qi, Qibin and Kilpel{\"a}inen, Tuomas O and Downer, Mary K and Tanaka, Toshiko and Smith, Caren E and Sluijs, Ivonne and Sonestedt, Emily and Chu, Audrey Y and Renstr{\"o}m, Frida and Lin, Xiaochen and Angquist, Lars H and Huang, Jinyan and Liu, Zhonghua and Li, Yanping and Asif Ali, Muhammad and Xu, Min and Ahluwalia, Tarunveer Singh and Boer, Jolanda M A and Chen, Peng and Daimon, Makoto and Eriksson, Johan and Perola, Markus and Friedlander, Yechiel and Gao, Yu-Tang and Heppe, Denise H M and Holloway, John W and Houston, Denise K and Kanoni, Stavroula and Kim, Yu-Mi and Laaksonen, Maarit A and J{\"a}{\"a}skel{\"a}inen, Tiina and Lee, Nanette R and Lehtim{\"a}ki, Terho and Lemaitre, Rozenn N and Lu, Wei and Luben, Robert N and Manichaikul, Ani and M{\"a}nnist{\"o}, Satu and Marques-Vidal, Pedro and Monda, Keri L and Ngwa, Julius S and Perusse, Louis and van Rooij, Frank J A and Xiang, Yong-Bing and Wen, Wanqing and Wojczynski, Mary K and Zhu, Jingwen and Borecki, Ingrid B and Bouchard, Claude and Cai, Qiuyin and Cooper, Cyrus and Dedoussis, George V and Deloukas, Panos and Ferrucci, Luigi and Forouhi, Nita G and Hansen, Torben and Christiansen, Lene and Hofman, Albert and Johansson, Ingegerd and J{\o}rgensen, Torben and Karasawa, Shigeru and Khaw, Kay-Tee and Kim, Mi-Kyung and Kristiansson, Kati and Li, Huaixing and Lin, Xu and Liu, Yongmei and Lohman, Kurt K and Long, Jirong and Mikkil{\"a}, Vera and Mozaffarian, Dariush and North, Kari and Pedersen, Oluf and Raitakari, Olli and Rissanen, Harri and Tuomilehto, Jaakko and van der Schouw, Yvonne T and Uitterlinden, Andr{\'e} G and Zillikens, M Carola and Franco, Oscar H and Shyong Tai, E and Ou Shu, Xiao and Siscovick, David S and Toft, Ulla and Verschuren, W M Monique and Vollenweider, Peter and Wareham, Nicholas J and Witteman, Jacqueline C M and Zheng, Wei and Ridker, Paul M and Kang, Jae H and Liang, Liming and Jensen, Majken K and Curhan, Gary C and Pasquale, Louis R and Hunter, David J and Mohlke, Karen L and Uusitupa, Matti and Cupples, L Adrienne and Rankinen, Tuomo and Orho-Melander, Marju and Wang, Tao and Chasman, Daniel I and Franks, Paul W and S{\o}rensen, Thorkild I A and Hu, Frank B and Loos, Ruth J F and Nettleton, Jennifer A and Qi, Lu}
}
@article {280796,
	title = {Anterior Segment Optical Coherence Tomography in the Long-Term Follow-up andDetection of Glaucoma in Boston TypeIKeratoprosthesis.},
	journal = {Ophthalmology},
	volume = {122},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {317-25},
	abstract = {PURPOSE: To evaluate the role of anterior segment (AS) optical coherence tomography (OCT) as a standardized method of imaging Boston type I keratoprosthesis (KPro) after surgery, particularly in the visualization of iris and angle structures. DESIGN: Prospective case series. PARTICIPANTS: Twenty patients who underwent KPro implantation in 1 eye. METHODS: Patients underwent AS OCT imaging before surgery. After KPro implantation, patients were imaged using the AS single, dual, and quad scans to obtain transverse images of the eye every 15{\textdegree} over 360{\textdegree}. High-resolution, corneal quad, and anterior chamber scans were also obtained. This imaging protocol allowed juxtaposition and comparison of the same imaging coordinates obtained before surgery and 3, 6, and 12 months after surgery. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), glaucoma progression on clinical examination and formal visual field testing, and anatomic angle changes on AS OCT defined by angle closure, peripheral anterior synechiae (PAS), iris-KPro backplate touch, and graft-host interface changes over time. RESULTS: Mean follow-up was 18.8{\textpm}3.2 months. The average preoperative VA was 1.9{\textpm}0.5 logarithm of the minimum angle of resolution. After surgery, VA improved to 1.0{\textpm}0.9 at last follow-up (P\&nbsp;= 0.002). Fourteen of 20 patients had glaucoma before surgery. After surgery, 5 of these patients deteriorated clinically and 1 de novo diagnosis of glaucoma was made. On OCT, the average total degrees of angle closure for all patients increased from 158.5{\textpm}158.9{\textdegree} before surgery to 205.4{\textpm}154.0{\textdegree} after surgery (P\&nbsp;= 0.04). The number of eyes with 360{\textdegree} of PAS increased from 6 of 20 before surgery to 9 of 20 after surgery. Iris-backplate touch was demonstrated in 5 of 20 patients, with an average area of involvement of 24.2{\textpm}36.2{\textdegree}. Overall, of the 12 of 20 patients with clear signs of anatomic angle narrowing and synechiae progression on imaging, 3 had glaucoma deterioration detected by clinical examination. In the other 9 patients, angle changes on OCT were not accompanied by any detectable clinical signs of glaucomatous deterioration. CONCLUSIONS: Anterior segment OCT can be used to observe anatomic changes after KPro implantation that cannot be detected otherwise. We were unable to demonstrate a correlation between anatomic features and clinical progression.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.08.007},
	author = {Qian, Cynthia X and Hassanaly, Salima and Harissi-Dagher, Mona}
}
@article {1589751,
	title = {Microinvasive Glaucoma Surgery in US Ophthalmology Residency: Surgical Case Log Cross-sectional Analysis and Proposal for New Glaucoma Procedure Classification},
	journal = {J Glaucoma},
	volume = {30},
	number = {7},
	year = {2021},
	month = {2021 Jul 01},
	pages = {621-628},
	abstract = {PRECIS: A cross-sectional sample of the US ophthalmology residency graduating class of 2018 revealed that 18.4\% of residents logged \&lt;5 traditional glaucoma surgeries, and 63.4\% logged at least 1 microinvasive glaucoma surgery (MIGS). PURPOSE: Describe the state of MIGS in US ophthalmology residency training and propose a glaucoma procedure classification system for residents{\textquoteright} surgical case logs. METHODS: Deidentified case logs from residents graduating in 2018 were requested from US residency program directors. RESULTS: Case logs were received for 152/488 (31\%) residents from 36/115 (31\%) programs. The mean number of traditional glaucoma surgeries per resident was 9.0{\textpm}5.9 (range: 0 to 31). The mean number of MIGS per resident was 5.2{\textpm}8.9 cases (range: 0 to 58). There were 28/152 (18.4\%) residents from 16/36 (44.4\%) programs who logged \&lt;5 traditional glaucoma surgeries as primary surgeon, and 3/152 (2.0\%) residents from 3/36 (8.3\%) programs who logged zero traditional glaucoma surgeries as primary surgeon. There were 98/152 (64.5\%) residents from 32/36 (88.8\%) programs who logged \&lt;5 MIGS as primary surgeon, and 48/152 (31.6\%) residents from 25 of 36 (69.4\%) programs who logged zero MIGS as primary surgeon. There were 104/152 (63.4\%) residents from 33/36 (91.6\%) programs who logged at least 1 MIGS as primary surgeon; there were 3/36 (8.3\%) residency programs where no resident logged any MIGS as primary surgeon. CONCLUSIONS: US ophthalmology residents{\textquoteright} MIGS experience varies widely. Residents can satisfy glaucoma surgery requirements with some MIGS, even in the absence of adequate traditional glaucoma surgeries. We propose a residency case log classification system that better reflects the growing role of MIGS in clinical practice and helps ophthalmic educators more accurately track procedures requiring related skills.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001846},
	author = {Qiu, Mary and Woreta, Fasika A and Boland, Michael V}
}
@article {1333944,
	title = {Measuring Pedestrian Collision Detection With Peripheral Field Loss and the Impact of Peripheral Prisms},
	journal = {Transl Vis Sci Technol},
	volume = {7},
	number = {5},
	year = {2018},
	month = {2018},
	pages = {1},
	abstract = {Purpose: Peripheral field loss (PFL) due to retinitis pigmentosa, choroideremia, or glaucoma often results in a highly constricted residual central field, which makes it difficult for patients to avoid collision with approaching pedestrians. We developed a virtual environment to evaluate the ability of patients to detect pedestrians and judge potential collisions. We validated the system with both PFL patients and normally sighted subjects with simulated PFL. We also tested whether properly placed high-power prisms may improve pedestrian detection. Methods: A virtual park-like open space was rendered using a driving simulator (configured for walking speeds), and pedestrians in testing scenarios appeared within and outside the residual central field. Nine normally sighted subjects and eight PFL patients performed the pedestrian detection and collision judgment tasks. The performance of the subjects with simulated PFL was further evaluated with field of view expanding prisms. Results: The virtual system for testing pedestrian detection and collision judgment was validated. The performance of PFL patients and normally sighted subjects with simulated PFL were similar. The prisms for simulated PFL improved detection rates, reduced detection response times, and supported reasonable collision judgments in the prism-expanded field; detections and collision judgments in the residual central field were not influenced negatively by the prisms. Conclusions: The scenarios in a virtual environment are suitable for evaluating PFL and the impact of field of view expanding devices. Translational Relevance: This study validated an objective means to evaluate field expansion devices in reproducible near-real-life settings.},
	issn = {2164-2591},
	doi = {10.1167/tvst.7.5.1},
	author = {Qiu, Cheng and Jung, Jae-Hyun and Tuccar-Burak, Merve and Spano, Lauren and Goldstein, Robert and Peli, Eli}
}
@article {1645478,
	title = {Ophthalmology Surgical Assessment of Tube Shunt Glaucoma Surgery},
	journal = {Ophthalmol Glaucoma},
	volume = {6},
	number = {1},
	year = {2023},
	month = {2023 Jan-Feb},
	pages = {100-105},
	abstract = {PURPOSE: To develop an internationally standardized and validated tool to assess skill in performing tube shunt surgery. DESIGN: A panel of 6 glaucoma surgeons developed a tool for assessing tube shunt surgery using a modified Dreyfus scale for skill acquisition. The tool was reviewed by a panel of 10 international content experts, and their comments were incorporated into the final rubric. PARTICIPANTS: A different panel of 8 international glaucoma specialists independently graded videos of surgical procedures performed by 6 surgeons at various levels of ophthalmic training. MAIN OUTCOME MEASURES: Inter-rater reliability for each step in the rubric was calculated. RESULTS: The tube shunt rubric contained 13 steps specific to tube shunt surgery and 7 global indices. The Cronbach α statistic, a measure of internal reliability, ranged from 0.75 to 0.97, indicating strong internal reliability for all 13 steps. CONCLUSIONS: The tube shunt assessment tool has face validity, content validity, and interobserver reliability, and can be used to assess tube shunt surgery skills. Further studies are required to determine predictive and construct validity.},
	keywords = {Education, Medical, Graduate, Educational Measurement, Glaucoma, Humans, Internship and Residency, Ophthalmology, Reproducibility of Results},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.06.007},
	author = {Qiu, Mary and Avdagic, Ema and Ramulu, Pradeep Y and Golnik, Karl and Boland, Michael V}
}
@article {1364529,
	title = {Calcineurin activation causes retinal ganglion cell degeneration},
	journal = {Mol Vis},
	volume = {18},
	year = {2012},
	month = {2012},
	pages = {2828-38},
	abstract = {PURPOSE: We previously reported that calcineurin, a Ca(2+)/calmodulin-dependent serine/threonine phosphatase, is activated and proposed that it participates in retinal ganglion cell (RGC) apoptosis in two rodent ocular hypertension models. In this study, we tested whether calcineurin activation by itself, even in the absence of ocular hypertension, is sufficient to cause RGC degeneration. METHODS: We compared RGC and optic nerve morphology after adeno-associated virus serotype 2 (AAV2)-mediated transduction of RGCs with constitutively active calcineurin (CaNCA) or unactivated, wild-type calcineurin (CaNwt). Retinas and optic nerves were harvested 7-16 weeks after injection of the AAV into mouse vitreous. In flatmounted retinas, the transduced RGCs were identified with immunohistochemistry. The morphology of the RGCs was revealed by immunostaining for neurofilament SMI32 or by using GFP-M transgenic mice. A modified Sholl analysis was applied to analyze the RGC dendritic morphology. Optic nerve damage was assessed with optic nerve grading according to the Morrison standard. RESULTS: CaNwt and CaNCA were highly expressed in the injected eyes. Compared to the CaNwt-expressing RGCs, the CaNCA-expressing RGCs had smaller somas, smaller dendritic field areas, shorter total dendrite lengths, and simpler dendritic branching patterns. At 16 weeks, the CaNCA-expressing eyes had greater optic nerve damage than the CaNwt-expressing eyes. CONCLUSIONS: Calcineurin activation is sufficient to cause RGC dendritic degeneration and optic nerve damage. These data support the hypothesis that calcineurin activation is an important mediator of RGC degeneration, and are consistent with the hypothesis that calcineurin activation may contribute to RGC neurodegeneration in glaucoma.},
	keywords = {Animals, Axons, Calcineurin, Dendrites, Dependovirus, Enzyme Activation, Genetic Vectors, Green Fluorescent Proteins, Immunohistochemistry, Intravitreal Injections, Mice, Mice, Transgenic, Nerve Degeneration, Optic Nerve, Retinal Degeneration, Retinal Ganglion Cells, Transduction, Genetic, Transgenes},
	issn = {1090-0535},
	author = {Qu, Juan and Matsouaka, Roland and Betensky, Rebecca A and Hyman, Bradley T and Grosskreutz, Cynthia L}
}
@article {1363188,
	title = {The Time Course of Gene Expression during Reactive Gliosis in the Optic Nerve},
	journal = {PLoS One},
	volume = {8},
	number = {6},
	year = {2013},
	month = {2013},
	pages = {e67094},
	abstract = {Reactive gliosis is a complex process that involves changes in gene expression and morphological remodeling. The mouse optic nerve, where astrocytes, microglia and oligodendrocytes interact with retinal ganglion cell axons and each other, is a particularly suitable model for studying the molecular mechanisms of reactive gliosis. We triggered gliosis at the mouse optic nerve head by retro orbital nerve crush. We followed the expression profiles of 14,000 genes from 1 day to 3 months, as the optic nerve formed a glial scar. The transcriptome showed profound changes. These were greatest shortly after injury; the numbers of differentially regulated genes then dropped, returning nearly to resting levels by 3 months. Different genes were modulated with very different time courses, and functionally distinct groups of genes responded in partially overlapping waves. These correspond roughly to two quick waves of inflammation and cell proliferation, a slow wave of tissue remodeling and debris removal, and a final stationary phase that primarily reflects permanent structural changes in the axons. Responses from astrocytes, microglia and oligodendrocytes were distinctively different, both molecularly and morphologically. Comparisons to other models of brain injury and to glaucoma indicated that the glial responses depended on both the tissue and the injury. Attempts to modulate glial function after axonal injuries should consider different mechanistic targets at different times following the insult.},
	keywords = {Animals, Disease Models, Animal, Disease Progression, Female, Gene Expression, Glaucoma, Gliosis, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Neuroglia, Neuronal Plasticity, Optic Nerve, Optic Nerve Injuries, Retina, Retinal Degeneration, Time Factors},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0067094},
	author = {Qu, Juan and Jakobs, Tatjana C}
}
@article {705121,
	title = {Update on ocular cicatricial pemphigoid and emerging treatments.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {3},
	year = {2016},
	month = {2016 May-Jun},
	pages = {314-7},
	abstract = {Mucous membrane pemphigoid is a systemic disorder that primarily affects mucous membranes. When localized to the conjunctiva, it is known as ocular cicatricial pemphigoid, a potentially blinding disease. Ocular cicatricial pemphigoid is an indication for systemic immunosuppressive treatment to achieve adequate remission. Immunosuppressive agents are selected with a "stepladder" approach, commencing with medications having the fewest side effects. We provide an update of the literature on immunomodulatory agents since 2011 as additional treatment modalities have been explored in the last 4 years.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2015.12.007},
	author = {Queisi, Munther M and Zein, Mike and Lamba, Neerav and Meese, Halea and Foster, Charles Stephen}
}
@article {1623355,
	title = {Re: Fairless et al.: Ophthalmology departments remain among the least diverse clinical departments at United States medical schools (Ophthalmology. 2021;128:1129-1134)},
	journal = {Ophthalmology},
	volume = {129},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {e7-e8},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.10.024},
	author = {Quillen, David A and Lee, Paul P and Miller, Joan W and Feldon, Steven E and of the Association of University Professors of Ophthalmology}
}
@article {469021,
	title = {Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease: A Cross-Sectional Study.},
	journal = {JAMA Neurol},
	volume = {72},
	number = {8},
	year = {2015},
	month = {2015 Aug 1},
	pages = {912-9},
	abstract = {IMPORTANCE: Brain imaging and fluid biomarkers are characterized in children at risk for autosomal dominant Alzheimer disease (ADAD). OBJECTIVE: To characterize and compare structural magnetic resonance imaging (MRI), resting-state and task-dependent functional MRI, and plasma amyloid-β (Aβ) measurements in presenilin 1 (PSEN1) E280A mutation-carrying and noncarrying children with ADAD. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional measures of structural and functional MRI and plasma Aβ assays were assessed in 18 PSEN1 E280A carriers and 19 noncarriers aged 9 to 17 years from a Colombian kindred with ADAD. Recruitment and data collection for this study were conducted at the University of Antioquia and the Hospital Pablo Tobon Uribe in Medell{\'\i}n, Colombia, between August 2011 and June 2012. MAIN OUTCOMES AND MEASURES: All participants had blood sampling, structural MRI, and functional MRI during associative memory encoding and resting-state and cognitive assessments. Outcome measures included plasma Aβ1-42 concentrations and Aβ1-42:Aβ1-40 ratios, memory encoding-dependent activation changes, resting-state connectivity, and regional gray matter volumes. Structural and functional MRI data were compared using automated brain mapping algorithms and search regions related to AD. RESULTS: Similar to findings in adult mutation carriers, in the later preclinical and clinical stages of ADAD, mutation-carrying children were distinguished from control individuals by significantly higher plasma Aβ1-42 levels (mean [SD]: carriers, 18.8 [5.1] pg/mL and noncarriers, 13.1 [3.2] pg/mL; P \&lt; .001) and Aβ1-42:Aβ1-40 ratios (mean [SD]: carriers, 0.32 [0.06] and noncarriers, 0.21 [0.03]; P \&lt; .001), as well as less memory encoding task-related deactivation in parietal regions (eg, mean [SD] parameter estimates for the right precuneus were -0.590 [0.50] for noncarriers and -0.087 [0.38] for carriers; P \&lt; .005 uncorrected). Unlike carriers in the later stages, mutation-carrying children demonstrated increased functional connectivity of the posterior cingulate cortex with medial temporal lobe regions (mean [SD] parameter estimates were 0.038 [0.070] for noncarriers and 0.190 [0.057] for carriers), as well as greater gray matter volumes in temporal regions (eg, left parahippocampus; P \&lt; . 049, corrected for multiple comparisons). CONCLUSIONS AND RELEVANCE: Children at genetic risk for ADAD have functional and structural brain changes and abnormal levels of plasma Aβ1-42. The extent to which the underlying brain changes are either neurodegenerative or developmental remains to be determined. This study provides additional information about the earliest known biomarker changes associated with ADAD.},
	issn = {2168-6157},
	doi = {10.1001/jamaneurol.2015.1099},
	author = {Quiroz, Yakeel T and Schultz, Aaron P and Chen, Kewei and Protas, Hillary D and Brickhouse, Michael and Fleisher, Adam S and Langbaum, Jessica B and Thiyyagura, Pradeep and Fagan, Anne M and Shah, Aarti R and Muniz, Martha and Arboleda-Velasquez, Joseph F and Munoz, Claudia and Garcia, Gloria and Acosta-Baena, Natalia and Giraldo, Margarita and Tirado, Victoria and Ram{\'\i}rez, Dora L and Tariot, Pierre N and Dickerson, Bradford C and Sperling, Reisa A and Lopera, Francisco and Reiman, Eric M}
}
@article {1661609,
	title = {Penetrating Keratoplasty: Indications and Graft Survival by Geographic Region},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {31-43},
	abstract = {Corneal transplantation, or penetrating keratoplasty (PK), is the most common form of solid-organ transplantation performed worldwide. Here, we evaluated the indications for PK and rates of transplant survival around the world by geographic region. We conducted a literature search of PubMed, MEDLINE, and Google Scholar databases and identified 155 relevant studies from 41 countries published between 1987 and 2021. The most common indications for PK were keratoconus in Europe, Africa, the Middle East, Australia, New Zealand, and Central and South America, bullous keratopathy in North America, and corneal scarring in Asia. The overall global mean graft survival rates at 1-, 2-, 3-, 5-, and 10-years were 88.6\%, 81.2\%, 78.9\%, 72.8\%, and 61.2\%, respectively. Through this systematic analysis of PK by region, we hope to bring a new perspective to the corneal transplantation literature and to potentially highlight global differences and unmet needs in patient care.},
	keywords = {Corneal Diseases, Corneal Transplantation, Graft Survival, Humans, Keratoconus, Keratoplasty, Penetrating, Retrospective Studies, Visual Acuity},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152710},
	author = {Qureshi, Sana and Dohlman, Thomas H}
}
@article {1629451,
	title = {Acute Calcific Band Keratopathy as an Adverse Effect of Recombinant Human Nerve Growth Factor (Cenegermin): A Multicenter Case Series},
	journal = {Cornea},
	volume = {41},
	number = {1},
	year = {2022},
	month = {2022 Jan 01},
	pages = {52-59},
	abstract = {PURPOSE: Cenegermin, (OXERVATE) a recently Food and Drug Administration-approved topical formulation of recombinant human nerve growth factor, has been used for the treatment of neurotrophic keratopathy (NK). Corneal deposits have been previously reported as a potential adverse effect; however, the clinical characteristics, visual significance, and treatment options have not been fully described. The purpose of this article is to better characterize corneal deposits occurring during treatment with cenegermin for neurotrophic keratopathy. METHODS: This was a retrospective, multicenter consecutive case series. RESULTS: We identified 5 patients from 3 institutions who developed a white opacity in varying layers of the cornea, consistent with calcium deposition, during treatment with cenegermin. In all cases, the opacity occurred rapidly over the course of a few weeks after initiation of treatment. Histopathologic examination of the cornea from one corneal patient demonstrated extensive calcification of the stroma extending to 90\% depth. Before treatment, all patients had stage 2 or 3 NK (Mackie classification). The deposits were visually significant in all patients and did not resolve after cessation of cenegermin. There were no differences in age, sex, etiology of the NK, corneal transplant status, or concurrent medications between the patients who developed a deposit and 15 other patients with stage 2 or 3 NK who did not. One patient was successfully treated with superficial keratectomy with ethylenediaminetetraacetic acid chelation, one patient underwent penetrating keratoplasty, and one patient received a Boston keratoprosthesis. CONCLUSIONS: We report the rapid onset of a corneal opacity after initiation of treatment with cenegermin in patients with stage 2 or 3 NK, consistent with acute calcific band keratopathy. This visually significant adverse finding has not previously been described. We could not identify any risk factors for development. We recommend close monitoring of patients receiving cenegermin therapy because the opacity may be irreversible and may require keratoplasty for visual rehabilitation.},
	keywords = {Acute Disease, Adult, Aged, Aged, 80 and over, Calcinosis, Cornea, Corneal Dystrophies, Hereditary, Corneal Opacity, Female, Humans, Male, Nerve Growth Factor, Prognosis, Recombinant Proteins, Retrospective Studies, Slit Lamp Microscopy, Tomography, Optical Coherence},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002767},
	author = {Qureshi, Sana and Ferguson, Tanner J and Lim, Mira and You, Jae Young and Goshe, Jeffrey M and Hood, Christopher T}
}
@article {1532345,
	title = {SARS-CoV-2 detection using isothermal amplification and a rapid, inexpensive protocol for sample inactivation and purification},
	journal = {Proc Natl Acad Sci U S A},
	year = {2020},
	month = {2020 Sep 08},
	abstract = {The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had an enormous impact on society worldwide, threatening the lives and livelihoods of many. The effects will continue to grow and worsen if economies begin to open without the proper precautions, including expanded diagnostic capabilities. To address this need for increased testing, we have developed a sensitive reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay compatible with current reagents, which utilizes a colorimetric readout in as little as 30 min. A rapid inactivation protocol capable of inactivating virions, as well as endogenous nucleases, was optimized to increase sensitivity and sample stability. This protocol, combined with the RT-LAMP assay, has a sensitivity of at least 50 viral RNA copies per microliter in a sample. To further increase the sensitivity, a purification protocol compatible with this inactivation method was developed. The inactivation and purification protocol, combined with the RT-LAMP assay, brings the sensitivity to at least 1 viral RNA copy per microliter in a sample. This simple inactivation and purification pipeline is inexpensive and compatible with other downstream RNA detection platforms and uses readily available reagents. It should increase the availability of SARS-CoV-2 testing as well as expand the settings in which this testing can be performed.},
	issn = {1091-6490},
	doi = {10.1073/pnas.2011221117},
	author = {Rabe, Brian A and Cepko, Constance}
}
@article {1363189,
	title = {Retinal blood vessel positional shifts and glaucoma progression},
	journal = {Ophthalmology},
	volume = {121},
	number = {4},
	year = {2014},
	month = {2014 Apr},
	pages = {842-8},
	abstract = {PURPOSE: To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with >=8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (\&lt;-0.02 decibels [dB]/year), moderate (-0.02 to\&nbsp;-0.65 dB/year), or fast (>=-0.65 dB/year) progression. To determine whether graders{\textquoteright} assessments of RBV positional shifts were false-positives, a control group consisting of 33 patients with glaucoma with 2 sets of photographs taken on the same day was included. METHODS: Masked graders reviewed serial photographs aligned with automated alternation flicker (EyeIC, Narbeth, PA) and assessed them for the presence of any discrete RBV positional shifts (2 graders) and for traditional measures of structural progression (2 graders), including neuroretinal rim loss, parapapillary atrophy progression, and disc hemorrhage (DH). MAIN OUTCOME MEASURES: Presence or absence of RBV positional shifts, rates of VF progression, and presence or absence of traditional measures of structural progression. RESULTS: A total of 158 image sets (125 longitudinal and 33 same-day controls) from patients with glaucoma were included. Retinal blood vessel shifts were noted in 33 of 125 (26.4\%) longitudinally followed glaucomatous eyes and 2 of 33 (6\%) same-day control patients (P\&nbsp;= 0.01). Agreement between graders I and II was 90.4\% (kappa=0.77; P\&lt; 0.001). Eyes with RBV positional change progressed more rapidly than those without (-0.55 vs.\&nbsp;-0.29 dB/year; 95\% confidence interval [CI], 0.03-0.48); P\&nbsp;= 0.03). Retinal blood vessel shift was present in 12.1\% of minimal progressors versus 31.5\% of moderate and fast progressors (P\&nbsp;= 0.04). Rate of VF progression was statistically associated with RBV shift (odds ratio [OR], 2.2; 95\% CI, 1.1-4.5; P\&nbsp;= 0.03). Other variables significantly associated with RBV shift included neuroretinal rim loss (OR, 21.9; 95\% CI, 5.7-83.6; P\&lt; 0.001) and DH (OR, 4.6; 95\% CI, 1.5-15.5; P\&lt; 0.01). A multivariable model revealed that rim loss and DH, but not rate of functional change, were significantly associated with RBV shift. CONCLUSIONS: Retinal blood vessel positional shifts occurred in eyes with functionally progressive glaucoma, neuroretinal rim loss, and DH. This is a novel clinical finding that could help identify glaucoma progression or individuals at higher risk for future progression.},
	keywords = {Cohort Studies, Disease Progression, False Positive Reactions, Female, Follow-Up Studies, Glaucoma, Open-Angle, Gonioscopy, Humans, Intraocular Pressure, Male, Middle Aged, Optic Disk, Optic Nerve Diseases, Photography, Predictive Value of Tests, Retinal Vessels, Retrospective Studies, Vision Disorders, Visual Fields},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2013.11.002},
	author = {Radcliffe, Nathan M and Smith, Scott D and Syed, Zeba A and Park, Sung Chul and Ehrlich, Joshua R and De Moraes, Carlos Gustavo and Liebmann, Jeffrey M and Ritch, Robert}
}
@article {1302166,
	title = {Laser Peripheral Iridotomy in Primary Angle Closure: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {125},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {1110-1120},
	abstract = {PURPOSE: To examine the efficacy and complications of laser peripheral iridotomy (LPI) in subjects with primary angle closure (PAC). METHODS: Literature searches in the PubMed and Cochrane databases were last conducted in August 2017 and yielded 300 unique citations. Of these, 36 met the inclusion criteria and were rated according to the strength of evidence; 6 articles were rated level I, 11 articles were rated level II, and 19 articles were rated level III. RESULTS: Reported outcomes were change in angle width, effect on intraocular pressure (IOP) control, disease progression, and complications. Most of the studies (29/36, 81\%) included only Asian subjects. Angle width (measured by gonioscopy, ultrasound biomicroscopy, and anterior segment OCT) increased after LPI in all stages of angle closure. Gonioscopically defined persistent angle closure after LPI was reported in 2\% to 57\% of eyes across the disease spectrum. Baseline factors associated with persistent angle closure included narrower angle and parameters representing nonpupillary block mechanisms of angle closure, such as a thick iris, an anteriorly positioned ciliary body, or a greater lens vault. After LPI, further treatment to control IOP was reported in 0\%-8\% of PAC suspect (PACS), 42\% to 67\% of PAC, 21\% to 47\% of acute PAC (APAC), and 83\%-100\% of PAC glaucoma (PACG) eyes. Progression to PACG ranged from 0\% to 0.3\% per year in PACS and 0\% to 4\% per year in PAC. Complications after LPI included IOP spike (8-17 mmHg increase from baseline in 6\%-10\%), dysphotopsia (2\%-11\%), anterior chamber bleeding (30\%-41\%), and cataract progression (23\%-39\%). CONCLUSIONS: Laser peripheral iridotomy increases angle width in all stages of primary angle closure and has a good safety profile. Most PACS eyes do not receive further intervention, whereas many PAC and APAC eyes, and most PACG eyes, receive further treatment. Progression to PACG is uncommon in PACS and PAC. There are limited data on the comparative efficacy of LPI versus other treatments for the various stages of angle closure; 1 randomized controlled trial each demonstrated superiority of cataract surgery over LPI in APAC and of clear lens extraction over LPI in PACG or PAC with IOP above 30 mmHg.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.01.015},
	author = {Radhakrishnan, Sunita and Chen, Philip P and Junk, Anna K and Nouri-Mahdavi, Kouros and Chen, Teresa C}
}
@article {1661600,
	title = {Deformation of Aflibercept and Ranibizumab Syringes Causes Variation in Intravitreal Injection Volume and Risks Retinal Tear Formation},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {4},
	year = {2022},
	month = {2022 Dec},
	pages = {100202},
	abstract = {PURPOSE: The intravitreal injection volume is known to vary with plunger alignment and the speed of injection. We investigated the role that syringe stopper deformation plays in allowing excess volumes to be injected into the eye and the potential for the vitreous humor to become incarcerated when excess force is released within the eye. DESIGN: Experimental study. METHODS: Aflibercept prefilled syringes (PFSs), ranibizumab PFSs, and 1-ml tuberculin (TB) syringes were subjected to increasing injection force to assess the extent to which each design allowed for excess volumes to be expelled after the stopper reached the bottom of the syringe barrel (i.e., after the 50-μl dose was expelled). MAIN OUTCOME MEASURES: Additional volume expelled with stopper deformation. RESULTS: Syringe stoppers are capable of deformation into the dead space when additional force is applied. This allows for progressively greater medication doses to be administered. At an additional force of 3.92 N after the syringe stopper came in contact with the bottom of the syringe barrel, the aflibercept PFSs, ranibizumab PFSs, and 1-ml TB syringes dispensed an additional 17.2\%, 11.4\%, and 0.8\% higher volume than the intended volume of 50 μl, respectively. Upon release of this force, a proportional volume was observed to be drawn back into the needle. CONCLUSIONS: The intravitreal injection volume varies with the force applied to fully depressed syringes because of syringe stopper deformation. We advise that performing forceful intravitreal injections be avoided to prevent excessive dosing of medication. We also caution that pressure applied to the plunger during intravitreal injections not be released while the needle is in the vitreous cavity to guard against vitreous incarceration, which could lead to retinal tear formation or detachment.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100202},
	author = {Raevis, Joseph J and Lemire, Colin A and Ramsey, David J and Riccobono, James and Gonzalez, Efren}
}
@article {1586174,
	title = {Automated Microaneurysm Counts on Ultrawide Field Color and Fluorescein Angiography Images},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {315-321},
	abstract = {BACKGROUND: The severity and extent of microaneurysms (MAs) have been used to determine diabetic retinopathy (DR) severity and estimate the risk of DR progression over time. The recent introduction of ultrawide field (UWF) imaging has allowed ophthalmologists to readily image nearly the entire retina. Manual counting of MAs, especially on UWF images, is laborious and time-consuming, limiting its potential use in clinical settings. Automated MA counting techniques are potentially more accurate and reproducible compared to manual methods. METHOD: Review of available literature on current techniques of automated MA counting techniques on both ultrawide field (UWF) color images (CI) and fluorescein angiography (FA) images. RESULTS: Automated MA counting techniques on UWF images are still in the early phases of development with UWF-FA counts being further along. Early studies have demonstrated that these techniques are accurate and reproducible. CONCLUSION: Automated techniques may be an appropriate option for detecting and quantifying MAs on UWF images, especially in eyes with earlier DR severity. Larger studies are needed to appropriately validate these techniques and determine if they add substantially to clinical practice compared to standard DR grading.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1897852},
	author = {Rageh, Abdulrahman and Ashraf, Mohamed and Fleming, Alan and Silva, Paolo S}
}
@article {1435413,
	title = {Post-Concussion: Receded Near Point of Convergence is Not Diagnostic of Convergence Insufficiency},
	journal = {Am J Ophthalmol},
	year = {2019},
	month = {2019 Apr 17},
	abstract = {PURPOSE: To determine the frequency of receded near point of convergence (NPC) in patients with chronic concussion-related symptoms, and among those with receded NPC to enumerate the frequency of convergence insufficiency and other oculomotor disorders. STUDY: Design: Retrospective cross-sectional study METHODS: Clinic charts were retrospectively reviewed for the prior 3.5 years to identify all patients \&lt;21 years old who were \&gt;28 days post-concussion, had chronic concussion-related symptoms, had normal visual acuity, and received a comprehensive sensorimotor examination. The frequency of receded NPC and oculomotor diagnoses were determined. RESULTS: Of the 83 eligible patients, 74 (89\%) had receded NPC. Of these, 70 (95\%) had oculomotor disorders; 30 (41\%) had disorders of accommodation only, 21 (28\%) had convergence insufficiency and accommodation deficits, and 6 (8\%) had convergence insufficiency only. Six (8\%) had a convergence deficit other than convergence insufficiency (all with concurrent accommodative disorders), 4 (5\%) had both a non-specific vergence dysfunction and accommodation deficits, 2 (3\%) had convergence excess only, and 1 (1\%) had both convergence excess and accommodative deficits. CONCLUSION: A receded NPC was present in the majority of young patients with chronic post-concussion symptoms. Associated with numerous underlying oculomotor dysfunctions, the clinical finding of a receded NPC is not synonymous with the diagnosis of convergence insufficiency. Because treatment options for the various oculomotor dysfunctions differ, it is prudent that these patients undergo a thorough examination of their vergence and accommodative systems so that an accurate diagnosis can be made and appropriate treatment prescribed.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.04.008},
	author = {Raghuram, Aparna and Cotter, Susan and Gowrisankaran, Sowjanya and Kanji, Jameel and Howell, David R and Meehan, William P and Shah, Ankoor S}
}
@article {1323940,
	title = {Frequency of Visual Deficits in Children With Developmental Dyslexia},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {10},
	year = {2018},
	month = {2018 Oct 01},
	pages = {1089-1095},
	abstract = {Importance: Developmental dyslexia (DD) is a specific learning disability of neurobiological origin whose core cognitive deficit is widely believed to involve language (phonological) processing. Although reading is also a visual task, the potential role of vision in DD has been controversial, and little is known about the integrity of visual function in individuals with DD. Objective: To assess the frequency of visual deficits (specifically vergence, accommodation, and ocular motor tracking) in children with DD compared with a control group of typically developing readers. Design, Setting, and Participants: A prospective, uncontrolled observational study was conducted from May 28 to October 17, 2016, in an outpatient ophthalmology ambulatory clinic among 29 children with DD and 33 typically developing (TD) children. Main Outcomes and Measures: Primary outcomes were frequencies of deficits in vergence (amplitude, fusional ranges, and facility), accommodation (amplitude, facility, and accuracy), and ocular motor tracking (Developmental Eye Movement test and Visagraph eye tracker). Results: Among the children with DD (10 girls and 19 boys; mean [SD] age, 10.3 [1.2] years) and the TD group (21 girls and 12 boys; mean [SD] age, 9.4 [1.4] years), accommodation deficits were more frequent in the DD group than the TD group (16 [55\%] vs 3 [9\%]; difference = 46\%; 95\% CI, 25\%-67\%; P \&lt; .001). For ocular motor tracking, 18 children in the DD group (62\%) had scores in the impaired range (in the Developmental Eye Movement test, Visagraph, or both) vs 5 children in the TD group (15\%) (difference, 47\%; 95\% CI, 25\%-69\%; P \&lt; .001). Vergence deficits occurred in 10 children in the DD group (34\%) and 5 children in the TD group (15\%) (difference, 19\%; 95\% CI, -2.2\% to 41\%; P = .08). In all, 23 children in the DD group (79\%) and 11 children in the TD group (33\%) had deficits in 1 or more domain of visual function (difference, 46\%; 95\% CI, 23\%-69\%; P \&lt; .001). Conclusions and Relevance: These findings suggest that deficits in visual function are far more prevalent in school-aged children with DD than in TD readers, but the possible cause and clinical relevance of these deficits are uncertain. Further study is needed to determine the extent to which treating these deficits can improve visual symptoms and/or reading parameters.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.2797},
	author = {Raghuram, Aparna and Gowrisankaran, Sowjanya and Swanson, Emily and Zurakowski, David and Hunter, David G and Waber, Deborah P}
}
@article {1363190,
	title = {Photoreceptor and postreceptor responses in congenital stationary night blindness},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {7},
	year = {2013},
	month = {2013 Jul 10},
	pages = {4648-58},
	abstract = {PURPOSE: To investigate photoreceptor and postreceptor retinal function in patients with congenital stationary night blindness (CSNB). METHODS: Forty-one patients with CSNB (ages 0.19-32 years) were studied. ERG responses to a series of full-field stimuli were obtained under scotopic and photopic conditions and were used to categorize the CSNB patients as complete (cCSNB) or incomplete (iCSNB). Rod and cone photoreceptor (R(ROD), S(ROD), R(CONE), S(CONE)) and rod-driven postreceptor (V(MAX), log σ) response parameters were calculated from the a- and b-waves. Cone-driven responses to 30 Hz flicker and ON and OFF responses to a long duration (150 ms) flash were also obtained. Dark-adapted thresholds were measured. Analysis of variance was used to compare data from patients with cCSNB, patients with iCSNB, and controls. RESULTS: We found significant reduction in saturated photoreceptor amplitude (R(ROD), R(CONE)) but normal photoreceptor sensitivity (S(ROD), S(CONE)) in both CSNB groups. Rod-driven postreceptor response amplitude (V(MAX)) and sensitivity (log σ) were significantly reduced in CSNB. Log σ was significantly worse in cCSNB than in iCSNB; this was the only scotopic parameter that differed between the two CSNB groups. Photopic b-wave amplitude increased monotonically with stimulus strength in CSNB patients rather than showing a normal photopic hill. The amplitude of the 30-Hz flicker response was reduced compared with controls, more so in iCSNB than in cCSNB. The mean dark-adapted threshold was significantly elevated in CSNB, more so in cCSNB than in iCSNB. CONCLUSIONS: These results are evidence of normal photoreceptor function (despite the low saturated photoresponse amplitude) and anomalous postreceptor retinal circuitry.},
	keywords = {Adolescent, Adult, Analysis of Variance, Child, Child, Preschool, Dark Adaptation, Electroretinography, Female, Humans, Infant, Male, Night Blindness, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, Sensory Thresholds, Young Adult},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12111},
	author = {Raghuram, Aparna and Hansen, Ronald M and Moskowitz, Anne and Fulton, Anne B}
}
@article {1402587,
	title = {Self-reported visual symptoms in children with developmental dyslexia},
	journal = {Vision Res},
	volume = {155},
	year = {2019},
	month = {2019 Feb},
	pages = {11-16},
	abstract = {Although there are many anecdotal reports of children with developmental dyslexia complaining of vision symptoms when reading, empirical studies are lacking. The primary aim of the present study was to document self-reported vision-related symptoms in children with developmental dyslexia and typically reading peers. We also explored whether vision symptoms were correlated with sensorimotor measures of vergence, accommodation and ocular motor tracking skills. Using a prospective group comparison observational design, we assessed 28 children with developmental dyslexia (DD) and 33 typically reading children (TR) 7-11 years of age. Participants completed psychoeducational testing, a comprehensive sensorimotor eye examination, and the Convergence Insufficiency Symptom Survey (CISS), which includes 9 items pertaining to vision-related symptoms (CISS-V) and 6 that could have cognitive influence (CISS-C). CISS-V were significantly greater in DD than TR children. Ocular motor tracking, assessed by an infra-red limbal eye tracker while reading text, was most clearly associated with the visual symptoms, but only within the DD group. Vision-related symptom surveys followed by a comprehensive eye examination with detailed evaluation of sensorimotor functioning for those who report a high prevalence of symptoms may be clinically relevant for children with DD.},
	issn = {1878-5646},
	doi = {10.1016/j.visres.2018.11.007},
	author = {Raghuram, Aparna and Hunter, David G and Gowrisankaran, Sowjanya and Waber, Deborah P}
}
@article {1439860,
	title = {Accurately Assessing Visual Deficits in Children With Developmental Dyslexia-Reply},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 May 30},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.1712},
	author = {Raghuram, Aparna and Hunter, David G and Waber, Deborah P}
}
@article {1363265,
	title = {Influence of aromatase absence on the gene expression and histology of the mouse meibomian gland},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {2},
	year = {2013},
	month = {2013 Feb 05},
	pages = {987-98},
	abstract = {PURPOSE: We hypothesize that aromatase, an enzyme that controls estrogen biosynthesis, plays a major role in the sex-related differences of the meibomian gland. To begin to test this hypothesis, we examined the influence of aromatase absence, which completely eliminates estrogen production, on glandular gene expression and histology in male and female mice. METHODS: Meibomian glands were obtained from adult, age-matched wild-type (WT) and aromatase knockout (ArKO) mice. Tissues were processed for histology or the isolation of total RNA, which was analyzed for differentially expressed mRNAs by using microarrays. RESULTS: Our results show that aromatase significantly influences the expression of more than a thousand genes in the meibomian gland. The nature of this effect is primarily sex-dependent. In addition, the influence of aromatase on sex-related differences in gene expression is predominantly genotype-specific. However, many of the sex-related variations in biological process, molecular function, and cellular component ontologies, as well as in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, are remarkably similar between WT and ArKO mice. The loss of aromatase activity has no obvious effect on the histology of meibomian glands in male or female mice. CONCLUSIONS: Our findings demonstrate that aromatase has a significant impact on gene expression in the meibomian gland. The nature of this influence is sex-dependent and genotype-specific; however, many of the sex-related variations in gene ontologies and KEGG pathways are similar between WT and ArKO mice. Consequently, it appears that aromatase, and by extension estrogen, do not play a major role in the sex-related differences of the mouse meibomian gland.},
	keywords = {Animals, Aromatase, Estrogens, Female, Gene Expression Profiling, Gene Expression Regulation, Genotype, Male, Meibomian Glands, Mice, Mice, Inbred BALB C, Microarray Analysis, RNA, Messenger},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-10992},
	author = {Rahimi Darabad, Raheleh and Suzuki, Tomo and Richards, Stephen M and Jensen, Roderick V and Jakobiec, Frederick A and Zakka, Fouad R and Liu, Shaohui and Sullivan, David A}
}
@article {303946,
	title = {Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?},
	journal = {Exp Eye Res},
	volume = {127},
	year = {2014},
	month = {2014 Oct},
	pages = {153-60},
	abstract = {Researchers have proposed that estrogen deficiency will lead to a Sj{\"o}gren{\textquoteright}s syndrome (SjS)-like lacrimal gland inflammation, aqueous tear deficiency and dry eye. The purpose of this study was to determine whether this proposal is correct. Lacrimal glands were obtained from adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice, in which estrogen synthesis is completely eliminated. Tissues were also obtained from autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mice as inflammation controls. Tear volumes in WT and ArKO mice were measured and glands were processed for molecular biological and histological evaluation. Our results demonstrate that estrogen absence does not lead to a SjS-like inflammation in lacrimal tissue or to an aqueous-deficient dry eye. There was no upregulation of genes associated with inflammatory pathways in lacrimal glands of male or female ArKO mice. Such inflammatory activity was prominent in autoimmune MRL/lpr tissues. We also found no evidence of inflammation in lacrimal gland tissue sections of estrogen-deficient mice, and tear volumes of ArKO males were actually increased as compared to those WT controls. Interestingly, our study did show that estrogen absence influences the expression of thousands of lacrimal gland genes, and that this impact is sex- and genotype-specific. Our findings demonstrate that estrogen absence is not a risk factor for the development of SjS-like lacrimal gland inflammation or for aqueous-deficient dry eye in mice.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2014.07.017},
	author = {Rahimi Darabad, Raheleh and Suzuki, Tomo and Richards, Stephen M and Jakobiec, Frederick A and Zakka, Fouad R and Barabino, Stefano and Sullivan, David A}
}
@article {1528399,
	title = {Potential small-molecule drugs as available weapons to fight novel coronavirus (2019-nCoV): A review},
	journal = {Cell Biochem Funct},
	volume = {39},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {4-9},
	abstract = {Since the new coronavirus known as 2019-nCoV (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has widely spread in Wuhan, China, with severe pneumonia, scientists and physicians have made remarkable efforts to use various options such as monoclonal antibodies, peptides, vaccines, small-molecule drugs and interferon therapies to control, prevent or treatment infections of 2019-nCoV. However, no vaccine or drug has yet been confirmed to completely treat 2019-nCoV. In this review, we focus on the use of potential available small-molecule drug candidates for treating infections caused by 2019-nCoV.},
	keywords = {Antiviral Agents, China, COVID-19, Humans, SARS-CoV-2},
	issn = {1099-0844},
	doi = {10.1002/cbf.3576},
	author = {Rahimkhoei, Vahid and Jabbari, Nassrollah and Nourani, Aynaz and Sharifi, Sina and Akbari, Ali}
}
@article {1263381,
	title = {Anticoagulation in Glaucoma Surgery},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 16},
	pages = {1-4},
	abstract = {Anticoagulation medications are used commonly, particularly in an elderly population. There are many systemic diseases and scenarios that require modulation of coagulation to prevent serious adverse outcomes. While there is some consensus about their use in cataract surgery, there is less certainty about their management with glaucoma surgery. Glaucoma surgery presents a unique challenge when considering anticoagulation. Currently, there is great diversity in surgeon practices regarding anticoagulation in glaucoma surgery. Based on available evidence, it is unclear whether it is beneficial to hold anticoagulation, with or without bridging therapy, leading up to a planned surgery. Considering the potential serious adverse outcomes related to holding anticoagulation therapy, altering these medications for glaucoma surgery should be done sparingly and in consultation with the primary prescriber of such medications.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353828},
	author = {Rahman, Shiraaz I and Turalba, Angela}
}
@article {1263386,
	title = {Postoperative Endophthalmitis: A Review of Risk Factors, Prophylaxis, Incidence, Microbiology, Treatment, and Outcomes},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 27},
	pages = {1-7},
	abstract = {Postoperative endophthalmitis is one of the most feared complications of intraocular surgery. The most common types of intraocular surgeries performed worldwide are cataract extraction, glaucoma drainage implants/trabeculectomy, and pars plana vitrectomy. This review will focus on the clinical features, risk factors, prophylaxis, and treatment of endophthalmitis in these three main intraocular surgeries.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353826},
	author = {Rahmani, Safa and Eliott, Dean}
}
@article {504101,
	title = {Ocular Metastatic Renal Carcinoma Presenting With Proptosis.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {31},
	number = {4},
	year = {2015},
	month = {2015 Jul-Aug},
	pages = {e100-8},
	abstract = {Metastatic renal carcinoma is the third most common source of ocular and second most common source of orbital metastases. This is the first published case of von Hippel-Lindau (vHL) disease that developed renal cell carcinoma metastatic to an eye with a retinal hemangioblastoma. A 73-year-old woman had a history of vHL disease that included prior retinal hemangioblastomas, 2 cerebellar hemangioblastomas, and bilateral renal cell carcinomas with sacral metastasis. After presenting with progressive, painful proptosis secondary to a large mass observable by ocular CT, an enucleation-orbitotomy was performed, and the surgical specimen was sent for histopathological analysis. The ophthalmic renal metastatic tumor, like the primary tumor, was a clear cell variant that involved both the eyeball and orbit in continuity. The intraocular component was larger than the extraocular portion, which was interpreted as an outward extension of an initial retinal metastasis that probably first settled within a hemangioblastoma. Clusters of ectatic ghost vessels with thickened walls produced by periodic acid Schiff-positive, redundant basement membrane material were partially infiltrated by tumor cells at their periphery, thereby lending some support for this hypothesis. Immunohistochemical positivity for the biomarkers cytokeratin 18, vimentin, carbonic anhydrase IX, PAX2, and PAX 8 confirmed the diagnosis. The patient has refused further treatment. Her anophthalmic socket has comfortably retained a porous polyethylene implant without clinical evidence of local recurrence during 5 months of follow up.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000119},
	author = {Rai, Ruju and Jakobiec, Frederick A and Fay, Aaron}
}
@article {313146,
	title = {Tick Infestation of the Eyelid With Histopathologic Characterization.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {3},
	year = {2016},
	month = {2016 May-Jun},
	pages = {e55-8},
	abstract = {Ocular tick infestation is a rare occurrence. The authors report a case that is unique for being the first published example from New England, for its chronic presentation, and for the inclusion of histopathologic analysis in its diagnostic workup. A 75-year-old man was evaluated for a persistent eyelid growth secondary to an incompletely removed tick that had attached 6 months earlier. The lesion was completely excised, and a partially destroyed arthropod was observed embedded within the tissue. Light microscopy demonstrated a mixed granulomatous reaction. Given the disruption of the tick{\textquoteright}s anatomy, speciation could not be performed. The patient had an uneventful recovery. A corresponding review of tick bites to the eye is provided.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000231},
	author = {Rai, Ruju and Yoon, Michael K and Stacy, Rebecca C}
}
@article {1333941,
	title = {Adherence to a Mediterranean diet, lifestyle and age-related macular degeneration: the Coimbra Eye Study - report 3},
	journal = {Acta Ophthalmol},
	volume = {96},
	number = {8},
	year = {2018},
	month = {2018 Dec},
	pages = {e926-e932},
	abstract = {PURPOSE: To characterize the lifestyle and nutritional risk profile associated with the Mediterranean diet in a Portuguese population with and without age-related macular degeneration (AMD). METHODS: Nested case-control study (n\&nbsp;=\&nbsp;883) within the Coimbra Eye Study, including 434 subjects with AMD and 449 age- and sex-matched subjects without AMD. All enrolled subjects underwent a full risk assessment, including lifestyle-related risk factors and a thorough food frequency questionnaire. This allowed us to build an adherence score to the Mediterranean diet (mediSCORE, range 0-9) constructed from individual food intakes. Food intake was also further analysed by conversion to micronutrient consumption. RESULTS: Our results suggest that physical activity has a protective role in AMD [p\&nbsp;=\&nbsp;0.018 after multivariate adjustment, OR: 0.69 (0.51-0.93)]. High (mediSCORE >=6) was also found to be protective [p\&nbsp;=\&nbsp;0.041, OR: 0.62 (95\% CI: 0.38-0.97)]. Food group analysis unveiled a specific protective role for increased fruits consumption (p\&nbsp;=\&nbsp;0.029). Finally, micronutrient analysis revealed a protective role associated with increased consumption of caffeine, fibres, beta-carotene, vitamin C and vitamin E (p\&nbsp;\&lt;\&nbsp;0.05). CONCLUSION: High mediSCORE appears to confer protection against the development of AMD in a Mediterranean population. This effect is driven by increased consumption of fruits and some antioxidant micronutrients, which emerged as statistically significant protective factors. Further studies are required to establish dietary recommendations with clinical application.},
	issn = {1755-3768},
	doi = {10.1111/aos.13775},
	author = {Raimundo, Miguel and Mira, Filipe and Cachulo, Maria da Luz and Barreto, Patr{\'\i}cia and Ribeiro, Lu{\'\i}sa and Farinha, Cl{\'a}udia and La{\'\i}ns, In{\^e}s and Nunes, Sandrina and Alves, Dalila and Figueira, Jo{\~a}o and Merle, B{\'e}n{\'e}dicte Mj and Delcourt, C{\'e}cile and Santos, L{\`e}lita and Silva, Rufino}
}
@article {882971,
	title = {Multidrug Intrinsic Resistance Factors in Staphylococcus aureus Identified by Profiling Fitness within High-Diversity Transposon Libraries.},
	journal = {MBio},
	volume = {7},
	number = {4},
	year = {2016},
	month = {2016},
	abstract = {UNLABELLED: Staphylococcus aureus is a leading cause of life-threatening infections worldwide. The MIC of an antibiotic against S.\&nbsp;aureus, as well as other microbes, is determined by the affinity of the antibiotic for its target in addition to a complex interplay of many other cellular factors. Identifying nontarget factors impacting resistance to multiple antibiotics could inform the design of new compounds and lead to more-effective antimicrobial strategies. We examined large collections of transposon insertion mutants in S.\&nbsp;aureus using transposon sequencing (Tn-Seq) to detect transposon mutants with reduced fitness in the presence of six clinically important antibiotics-ciprofloxacin, daptomycin, gentamicin, linezolid, oxacillin, and vancomycin. This approach allowed us to assess the relative fitness of many mutants simultaneously within these libraries. We identified pathways/genes previously known to be involved in resistance to individual antibiotics, including graRS and vraFG (graRS/vraFG), mprF, and fmtA, validating the approach, and found several to be important across multiple classes of antibiotics. We also identified two new, previously uncharacterized genes, SAOUHSC_01025 and SAOUHSC_01050, encoding polytopic membrane proteins, as important in limiting the effectiveness of multiple antibiotics. Machine learning identified similarities in the fitness profiles of graXRS/vraFG, SAOUHSC_01025, and SAOUHSC_01050 mutants upon antibiotic treatment, connecting these genes of unknown function to modulation of crucial cell envelope properties. Therapeutic strategies that combine a known antibiotic with a compound that targets these or other intrinsic resistance factors may be of value for enhancing the activity of existing antibiotics for treating otherwise-resistant S.\&nbsp;aureus strains. IMPORTANCE: Bacterial resistance to every major class of antibiotics has emerged, and we are entering a "post-antibiotic era" where relatively minor infections can lead to serious complications or even death. The utility of an antibiotic for a specific pathogen is limited by both intrinsic and acquired factors. Identifying the repertoire of intrinsic resistance factors of an antibiotic for Staphylococcus aureus, a leading cause of community- and hospital-acquired infections, would inform the design of new drugs as well as the identification of compounds that enhance the activity of existing drugs. To identify factors that limit the activity of antibiotics against S.\&nbsp;aureus, we used Tn-Seq to simultaneously assess fitness of transposon mutants in every nonessential gene in the presence of six clinically important antibiotics. This work provides an efficient approach for identifying promising targets for drugs that can enhance susceptibility or restore sensitivity to existing antibiotics.},
	issn = {2150-7511},
	doi = {10.1128/mBio.00950-16},
	author = {Rajagopal, Mithila and Martin, Melissa J and Santiago, Marina and Lee, Wonsik and Kos, Veronica N and Meredith, Tim and Gilmore, Michael S and Walker, Suzanne}
}
@article {1364530,
	title = {Heat shock protein 27 mediated signaling in viral infection},
	journal = {Biochemistry},
	volume = {51},
	number = {28},
	year = {2012},
	month = {2012 Jul 17},
	pages = {5695-702},
	abstract = {Heat shock proteins (HSPs) play a critical role in many intracellular processes, including apoptosis and delivery of other proteins to intracellular compartments. Small HSPs have been shown previously to participate in many cellular functions, including IL-8 induction. Human adenovirus infection activates intracellular signaling, involving particularly the c-Src and mitogen-activated protein kinases [Natarajan, K., et al. (2003) J. Immunol. 170, 6234-6243]. HSP27 and MK2 are also phosphorylated, and c-Src, and its downstream targets, p38, ERK1/2, and c-Jun-terminal kinase (JNK), differentially mediate IL-8 and MCP-1 expression. Specifically, activation and translocation of transcription factor NFκB-p65 occurs in a p38-dependent fashion [Rajaiya, J., et al. (2009) Mol. Vision 15, 2879-2889]. Herein, we report a novel role for HSP27 in an association of p38 with NFκB-p65. Immunoprecipitation assays of virus-infected but not mock-infected cells revealed a signaling complex including p38 and NFκB-p65. Transfection with HSP27 short interfering RNA (siRNA) but not scrambled RNA disrupted this association and reduced the level of IL-8 expression. Transfection with HSP27 siRNA also reduced the level of nuclear localization of NFκB-p65 and p38. By use of tagged p38 mutants, we found that amino acids 279-347 of p38 are necessary for the association of p38 with NFκB-p65. These studies strongly suggest that HSP27, p38, and NFκB-p65 form a signalosome in virus-infected cells and influence downstream expression of pro-inflammatory mediators.},
	keywords = {Adenovirus Infections, Human, Adenoviruses, Human, Cells, Cultured, Chemokines, HSP27 Heat-Shock Proteins, Humans, Keratinocytes, NF-kappa B p50 Subunit, p38 Mitogen-Activated Protein Kinases, Protein Transport, Signal Transduction},
	issn = {1520-4995},
	doi = {10.1021/bi3007127},
	author = {Rajaiya, Jaya and Yousuf, Mohammad A and Singh, Gurdeep and Stanish, Heather and Chodosh, James}
}
@article {439686,
	title = {Novel model of innate immunity in corneal infection.},
	journal = {In Vitro Cell Dev Biol Anim},
	year = {2015},
	month = {2015 May 15},
	abstract = {The cornea functions as the major refractive interface for vision and protects the internal eye from insult. Current understanding of innate immune responses to corneal infection derives from a synthesis of in vitro and in vivo analyses. However, monolayer cell cultures and mouse models do not accurately duplicate all aspects of innate immunity in human patients. Here, we describe a three-dimensional culture system that incorporates human cells and extracellular matrix to more completely simulate the human cornea for studies of infection. Human corneal stromal fibroblasts were mixed with type I collagen in 3-μm pore size transwell inserts, and overlayed with Matrigel to simulate a human corneal stroma and epithelial basement membrane. These were then infected with a cornea-tropic adenovirus, and exposed on their inferior side to leukocytes derived from human peripheral blood. Subsequent analyses were performed with histology, confocal microscopy, ELISA, and fluorescence-activated cell sorting (FACS). CXCL8, a neutrophil chemokine shown previously as the first cytokine induced in infection of human corneal cells, increased upon adenovirus infection of facsimiles in a dose-responsive fashion. Myeloperoxidase-positive cells infiltrated infected corneal facsimiles in a sub-Matrigel location, possibly due to CXCL8 colocalization with heparan sulfate, a Matrigel constituent. Cellular infiltration was significantly inhibited by treatment with chemical inhibitors of p38 MAPK and Src kinase, both constituents of a signaling cascade previously suggested to regulate inflammation after adenovirus infection. FACS analysis determined that both virus and corneal fibroblasts were necessary for the induction of leukocyte migration into the facsimiles. The corneal facsimile, literally a cornea in a test tube, permits mechanistic studies on human tissue in a highly tractable system.},
	issn = {1543-706X},
	doi = {10.1007/s11626-015-9910-2},
	author = {Rajaiya, Jaya and Zhou, Xiaohong and Barequet, Irina and Gilmore, Michael S and Chodosh, James}
}
@article {1782326,
	title = {TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study},
	journal = {J Transl Med},
	volume = {21},
	number = {1},
	year = {2023},
	month = {2023 Nov 24},
	pages = {847},
	abstract = {BACKGROUND: In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm{\textquoteright}s canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP. However, human genetic support for a causal role of TIE1 and TEK signalling in lowering IOP is currently lacking. METHODS: GWAS summary statistics were obtained for plasma soluble TIE1 (sTIE1) protein levels (N = 35,559), soluble TEK (sTEK) protein levels (N = 35,559), IOP (N = 139,555) and POAG (Ncases = 16,677, Ncontrols = 199,580). Mendelian randomization (MR) was performed to estimate the association of genetically proxied TIE1 and TEK protein levels with IOP and POAG liability. Where significant MR estimates were obtained, genetic colocalization was performed to assess the probability of a shared causal variant (PPshared) versus distinct (PPdistinct) causal variants underlying TIE1/TEK signalling and the outcome. Publicly available single-nucleus RNA-sequencing data were leveraged to investigate differential expression of TIE1 and TEK in the human ocular anterior segment. RESULTS: Increased genetically proxied TIE1 signalling and TEK signalling associated with a reduction in IOP (- 0.21\&nbsp;mmHg per SD increase in sTIE1, 95\% CI = - 0.09 to - 0.33\&nbsp;mmHg, P = 6.57 {\texttimes} 10-4, and - 0.14\&nbsp;mmHg per SD decrease in sTEK, 95\% CI = - 0.03 to - 0.25\&nbsp;mmHg, P = 0.011), but not with POAG liability. Colocalization analysis found that the probability of a shared causal variant was greater for TIE1 and IOP than for TEK and IOP (PPshared/(PPdistinct + PPshared) = 0.98 for TIE1 and 0.30 for TEK). In the anterior segment, TIE1 and TEK were preferentially expressed in SC, lymphatic, and vascular endothelium. CONCLUSIONS: This study provides novel human genetic support for a causal role of both TIE1 and TEK signalling in regulating IOP. Here, combined evidence from cis-MR and colocalization analyses provide stronger support for TIE1 than TEK as a potential IOP-lowering therapeutic target.},
	keywords = {Angiopoietins, Animals, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Mendelian Randomization Analysis},
	issn = {1479-5876},
	doi = {10.1186/s12967-023-04737-9},
	author = {Rajasundaram, Skanda and Zebardast, Nazlee and Mehta, Puja and Khawaja, Anthony P and Warwick, Alasdair and Duchinski, Katherine and Burgess, Stephen and Gill, Dipender and Segr{\`e}, Ayellet V and Wiggs, Janey}
}
@article {931141,
	title = {Evaluation of dose and safety of AAV7m8 and AAV8BP2 in the non-human primate retina.},
	journal = {Hum Gene Ther},
	year = {2016},
	month = {2016 Oct 18},
	abstract = {Within the next decade, we will see many gene therapy clinical trials for eye diseases progress, which may lead to treatments for thousands of visually impaired people around the world. To target retinal diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in pre-clinical mouse studies. Because there are numerous anatomic, and physiologic differences between the eyes of mice and {\textquoteright}men{\textquoteright} and because surgical delivery approaches and immunologic responses also differ between these species, we evaluated the transduction characteristics of two promising new serotypes AAV7m8 and AAV8BP2, in retinas of animals that are most similar to those of humans: non-human primates (NHPs). We report that while AAV7m8 efficiently targets a variety of cell types by subretinal injection in NHPs, transduction after intravitreal delivery was mostly restricted to the inner retina at lower doses that did not induce an immune response. AAV8BP2 targets the cone photoreceptors efficiently but bipolar cells inefficiently by subretinal injection. Additionally, we observed transduction of both serotypes in the anterior chamber of the eye and the optic pathway of the brain post intravitreal delivery. Finally, we assessed immunogenicity, keeping in mind that these AAV capsids may be used in future clinical trials. We found that AAV8BP2 had a better safety profile compared to AAV7m8 even at the highest doses administered. Our studies underscore the differences in AAV transduction between mice and primates highlighting the importance of careful evaluation of therapeutic vectors in NHPs prior to moving into clinical trials.},
	issn = {1557-7422},
	doi = {10.1089/hum.2016.111},
	author = {Ramachandran, Pavitra and Lee, Vivian and Wei, Zhangyong and Song, Ji Yun and Casal, Giulia and Cronin, Therese and Willett, Keirnan and Huckfeldt, Rachel and Morgan, Jessica I W and Aleman, Tomas S and Maguire, Albert M and Bennett, Jean}
}
@article {1677731,
	title = {Modelling eye lengths and refractions in the periphery},
	journal = {Ophthalmic Physiol Opt},
	volume = {43},
	number = {4},
	year = {2023},
	month = {2023 Jul},
	pages = {815-826},
	abstract = {PURPOSE: To create a simplified model of the eye by which we can specify a key optical characteristic of the crystalline lens, namely its power. METHODS: Cycloplegic refraction and axial length were obtained in 60 eyes of 30 healthy subjects at eccentricities spanning 40{\textdegree} nasal to 40{\textdegree} temporal and were fitted with a three-dimensional parabolic model. Keratometric values and geometric distances to the cornea, lens and retina from 45 eyes supplied a numerical ray tracing model. Posterior lens curvature (PLC) was found by optimising the refractive data using a fixed lens equivalent refractive index ( n eq ). Then, n eq was found using a fixed PLC. RESULTS: Eccentric refractive errors were relatively hyperopic in eyes with central refractions <=-1.44 D but relatively myopic in emmetropes and hyperopes. Posterior lens power, which cannot be measured directly, was derived from the optimised model lens. There was a weak, negative association between derived PLC and central spherical equivalent refraction. Regardless of refractive error, the posterior retinal curvature remained fixed. CONCLUSIONS: By combining both on- and off-axis refractions and eye length measurements, this simplified model enabled the specification of posterior lens power and captured off-axis lenticular characteristics. The broad distribution in off-axis lens power represents a notable contrast to the relative stability of retinal curvature.},
	keywords = {Contact Lenses, Eye, Humans, Hyperopia, Myopia, Refraction, Ocular, Refractive Errors, Retina},
	issn = {1475-1313},
	doi = {10.1111/opo.13133},
	author = {Ramamirtham, Ramkumar and Akula, James D and Curran, Amber-Lee K and Szczygiel, Justyna and Lancos, Annie M and Grytz, Rafael and Ferguson, R Daniel and Fulton, Anne B}
}
@article {959466,
	title = {IQGAP1 makes PI(3)K signalling as easy as PIP, PIP2, PIP3.},
	journal = {Nat Cell Biol},
	volume = {18},
	number = {12},
	year = {2016},
	month = {2016 Nov 29},
	pages = {1263-1265},
	abstract = {Despite being one of the most studied signalling pathways, precisely how phospholipid synthesis is regulated in the phosphoinositide signalling cascade remains unclear. The scaffold protein IQGAP1 is now shown to orchestrate the assembly of a multi-enzyme complex that streamlines PtdIns(3,4,5)P3 synthesis to facilitate Akt activation in response to extracellular stimuli.},
	issn = {1476-4679},
	doi = {10.1038/ncb3440},
	author = {Rameh, Lucia E and Mackey, Ashley M}
}
@article {1698341,
	title = {Thyroid Eye Disease and its Vision-Threatening Manifestations in the Academy IRIS Registry: 2014-2018},
	journal = {Am J Ophthalmol},
	volume = {253},
	year = {2023},
	month = {2023 Sep},
	pages = {74-85},
	abstract = {PURPOSE: To evaluate prevalence of thyroid eye disease (TED) and associated factors in the American Academy of Ophthalmology IRIS(R) Registry (Intelligent Research in Sight). DESIGN: Cross-sectional analysis of the IRIS Registry. METHODS: IRIS Registry patients (18-90 years old) were classified as TED (ICD-9: 242.00, ICD-10: E05.00 on >=2 visits) or non-TED cases, and prevalence was estimated. Odds ratios (OR) and 95\% Confidence Intervals (CIs) were estimated using logistic regression. RESULTS: 41,211 TED patients were identified. TED prevalence was 0.09\%, showed a unimodal age distribution (highest prevalence in ages 50-59 years (y) (0.12\%)), higher rates in females than males (0.12\% vs. 0.04\%) and in non-Hispanics than Hispanics (0.10\% vs. 0.05\%). Prevalence differed by race (from 0.08\% in Asians to 0.12\% in Black/African-Americans), with varying peak ages of prevalence. Factors associated with TED in multivariate analysis included age: ((18-\&lt;30y (reference), 30-39y: OR (95\%CI) 2.2 (2.0, 2.4), 40-49y: 2.9 (2.7,3.1), 50-59y: 3.3 (3.1, 3. 5), 60-69y: 2.7 (2.54, 2.85), 70+: 1.5 (1.46, 1.64)); female sex vs male (reference), 3.5 (3.4,3.6), race: White (reference), Blacks: 1.1 (1.1,1.2), Asian: 0.9 (0.8,0.9), Hispanic ethnicity vs not Hispanic (reference), 0.68 (0.6,0.7), smoking status: (never (ref), former: 1.64 (1.6,1.7), current 2.16: (2.1,2.2)) and Type 1 diabetes (yes vs no (reference): 1.87 (1.8, 1.9). CONCLUSIONS: This epidemiologic profile of TED includes new observations such as a unimodal age distribution and racial variation in prevalence. Associations with female sex, smoking, and Type 1 diabetes are consistent with prior reports. These findings raise novel questions about TED in different populations.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Diabetes Mellitus, Type 1, ethnicity, Female, Graves Ophthalmopathy, Humans, Male, Middle Aged, Registries, United States, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.04.013},
	author = {Ramesh, Sathyadeepak and Zhang, Qiang Ed and Sharpe, James and Penne, Robert and Haller, Julia and Lum, Flora and Lee, Aaron Y and Lee, Cecilia S and Pershing, Suzann and Miller, Joan W and Lorch, Alice and Hyman, Leslie and IRIS RESEARCH ANALYTIC CENTER CONSORTIUM}
}
@article {931146,
	title = {Evidence-Based Treatment of Diabetic Retinopathy.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	month = {2017},
	pages = {67-74},
	abstract = {Diabetic retinopathy (DR) is the most frequent microvascular complication from diabetes and requires annual screening and at least annual follow-up. A systemic approach to optimize blood glucose and blood pressure may halt progression to severe stages of DR and obviate the need for ocular treatment. Although there is evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes with nonproliferative DR (NPDR), these therapies are not standard care for NPDR at this time. Some patients with severe NPDR, especially those with type 2 diabetes, benefit from early panretinal photocoagulation (PRP). Once DR progresses to proliferative DR (PDR), treatment is often necessary to prevent visual loss. PRP remains mainstay treatment for PDR with high-risk characteristics. However, intravitreous antiVEGF injections appear to be a safe and effective treatment alternative for PDR through at least two years. Vitreoretinal surgery is indicated for PDR cases with non-clearing vitreous hemorrhage and/or tractional retinal detachment.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228397},
	author = {Rami, Hala El and Barham, Rasha and Sun, Jennifer K and Silva, Paolo S}
}
@article {1538352,
	title = {In vivo measurement of shear modulus of the human cornea using optical coherence elastography},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Oct 15},
	pages = {17366},
	abstract = {Corneal stiffness plays a critical role in shaping the cornea with respect to intraocular pressure and physical interventions. However, it remains difficult to measure the mechanical properties noninvasively. Here, we report the first measurement of shear modulus in human corneas in vivo using optical coherence elastography (OCE) based on surface elastic waves. In a pilot study of 12 healthy subjects aged between 25 and 67, the Rayleigh-wave speed was 7.86 {\textpm} 0.75\&nbsp;m/s, corresponding to a shear modulus of 72 {\textpm} 14\&nbsp;kPa. Our data reveal two unexpected trends: no correlation was found between the wave speed and IOP between 13-18\&nbsp;mmHg, and shear modulus decreases with age (- 0.32 {\textpm} 0.17\&nbsp;m/s per decade). We propose that shear stiffness is governed by the interfibrillar matrix, whereas tensile strength is dominated by collagen fibrils. Rayleigh-wave OCE may prove useful for clinical diagnosis, refractive surgeries, and treatment monitoring.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-74383-4},
	author = {Ramier, Antoine and Eltony, Amira M and Chen, YiTong and Clouser, Fatima and Birkenfeld, Judith S and Watts, Amy and Yun, Seok-Hyun}
}
@article {1059801,
	title = {The 5{\textquoteright}UTR in human adenoviruses: leader diversity in late gene expression},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Apr 04},
	pages = {618},
	abstract = {Human adenoviruses (HAdVs) shut down host cellular cap-dependent mRNA translation while initiating the translation of viral late mRNAs in a cap-independent manner. HAdV 5{\textquoteright}\&nbsp;untranslated regions (5{\textquoteright}UTRs) are crucial for cap-independent initiation, and influence mRNA localization and stability. However, HAdV translational regulation remains relatively uncharacterized. The HAdV tripartite leader (TPL), composed of three introns (TPL 1-3), is critical to the translation of HAdV late mRNA. Herein, we annotated and analyzed 72 HAdV genotypes for the HAdV TPL and another previously described leader, the i-leader. Using HAdV species D, type 37 (HAdV-D37), we show by reverse transcription PCR and Sanger sequencing that mRNAs of the HAdV-D37 E3 transcription unit are spliced to the TPL. We also identified a polycistronic mRNA for RID-α and RID-β. Analysis of the i-leader revealed a potential open reading frame within the leader sequence and the termination of this potential protein in TPL3. A potential new leader embedded within the E3 region was also detected and tentatively named the j-leader. These results suggest an underappreciated complexity of post-transcriptional regulation, and the importance of HAdV 5{\textquoteright}UTRs for precisely coordinated viral protein expression along the path from genotype to phenotype.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-00747-y},
	author = {Ramke, Mirja and Lee, Jeong Yoon and Dyer, David W and Seto, Donald and Rajaiya, Jaya and Chodosh, James}
}
@article {1629446,
	title = {Grand Challenges in global eye health: a global prioritisation process using Delphi method},
	journal = {Lancet Healthy Longev},
	volume = {3},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {e31-e41},
	abstract = {Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46\%) of 336 were women, 180 (54\%) were men. The proportion of participants who worked in each region ranged from 104 (31\%) in sub-Saharan Africa to 21 (6\%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.},
	issn = {2666-7568},
	doi = {10.1016/S2666-7568(21)00302-0},
	author = {Ramke, Jacqueline and Evans, Jennifer R and Habtamu, Esmael and Mwangi, Nyawira and Silva, Juan Carlos and Swenor, Bonnielin K and Congdon, Nathan and Faal, Hannah B and Foster, Allen and Friedman, David S and Gichuhi, Stephen and Jonas, Jost B and Khaw, Peng T and Kyari, Fatima and Murthy, Gudlavalleti V S and Wang, Ningli and Wong, Tien Y and Wormald, Richard and Yusufu, Mayinuer and Taylor, Hugh and Resnikoff, Serge and West, Sheila K and Burton, Matthew J and Grand Challenges in Global Eye Health study group}
}
@article {742306,
	title = {Resident corneal c-fms(+) macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis.},
	journal = {Exp Eye Res},
	volume = {147},
	year = {2016},
	month = {2016 Jun},
	pages = {144-7},
	abstract = {The cornea contains a heterogeneous population of antigen-presenting cells with the capacity to contribute to immune responses. Adenovirus keratitis is a severe corneal infection with acute and chronic phases. The role of resident corneal antigen-presenting cells in adenovirus keratitis has not been studied. We utilized transgenic MaFIA mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, in a mouse model of adenovirus keratitis. Clinical keratitis and recruitment of myeloperoxidase and CD45(+) cells were diminished in c-fms depleted, adenovirus infected mice, as compared to controls, consistent with a role for myeloid-lineage cells in adenovirus keratitis.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2016.05.016},
	author = {Ramke, Mirja and Zhou, Xiaohong and Materne, Emma Caroline and Rajaiya, Jaya and Chodosh, James}
}
@article {1688306,
	title = {Overlap of Genetic Loci for Central Serous Chorioretinopathy With Age-Related Macular Degeneration},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {5},
	year = {2023},
	month = {2023 May 01},
	pages = {449-457},
	abstract = {IMPORTANCE: Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases. OBJECTIVE: To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD. DESIGN, SETTING, AND PARTICIPANTS: Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in a meta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022. MAIN OUTCOMES AND MEASURES: Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by a meta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study. RESULTS: A total of 1176 patients with CSC and 526 787 controls (312 162 female [59.3\%]) were included in this analysis: 552 patients with CSC and 343 461 controls were identified in the FinnGen study, 103 patients with CSC and 178 573 controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in a meta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P = .004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P \&lt; 7.1 {\texttimes} 10-20). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95\% CI, 0.70-0.83 per +1 SD in AMD-PGS; P = 7.4 {\texttimes} 10-10). This association may have been mediated by loci containing complement genes. CONCLUSIONS AND RELEVANCE: In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.},
	keywords = {Central Serous Chorioretinopathy, Endothelial Cells, Female, Genetic Background, Genetic Loci, Genome-Wide Association Study, Humans, Macular Degeneration},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.0706},
	author = {R{\"a}m{\"o}, Joel T and Abner, Erik and van Dijk, Elon H C and Wang, Xin and Brinks, Joost and Nikopensius, Tiit and N{\~o}ukas, Margit and Marjonen, Heidi and Silander, Kaisa and Jukarainen, Sakari and Kiiskinen, Tuomo and Choi, Seung Hoan and Kajanne, Risto and Mehtonen, Juha and Palta, Priit and Lubitz, Steven A and Kaarniranta, Kai and Sobrin, Lucia and Kurki, Mitja and Yzer, Suzanne and Ellinor, Patrick T and Esko, T{\~o}nu and Daly, Mark J and den Hollander, Anneke I and Palotie, Aarno and Turunen, Joni A and Boon, Camiel J F and Rossin, Elizabeth J and FinnGen study and Estonian Biobank Research Team}
}
@article {1424814,
	title = {PolyGlcNAc-containing exopolymers enable surface penetration by non-motile Enterococcus faecalis},
	journal = {PLoS Pathog},
	volume = {15},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {e1007571},
	abstract = {Bacterial pathogens have evolved strategies that enable them to invade tissues and spread within the host. Enterococcus faecalis is a leading cause of local and disseminated multidrug-resistant hospital infections, but the molecular mechanisms used by this non-motile bacterium to penetrate surfaces and translocate through tissues remain largely unexplored. Here we present experimental evidence indicating that E. faecalis generates exopolysaccharides containing β-1,6-linked poly-N-acetylglucosamine (polyGlcNAc) as a mechanism to successfully penetrate semisolid surfaces and translocate through human epithelial cell monolayers. Genetic screening and molecular analyses of mutant strains identified glnA, rpiA and epaX as genes critically required for optimal E. faecalis penetration and translocation. Mechanistically, GlnA and RpiA cooperated to generate uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) that was utilized by EpaX to synthesize polyGlcNAc-containing polymers. Notably, exogenous supplementation with polymeric N-acetylglucosamine (PNAG) restored surface penetration by E. faecalis mutants devoid of EpaX. Our study uncovers an unexpected mechanism whereby the RpiA-GlnA-EpaX metabolic axis enables production of polyGlcNAc-containing polysaccharides that endow E. faecalis with the ability to penetrate surfaces. Hence, targeting carbohydrate metabolism or inhibiting biosynthesis of polyGlcNAc-containing exopolymers may represent a new strategy to more effectively confront enterococcal infections in the clinic.},
	issn = {1553-7374},
	doi = {10.1371/journal.ppat.1007571},
	author = {Ramos, Yusibeska and Rocha, Jorge and Hael, Ana L and van Gestel, Jordi and Vlamakis, Hera and Cywes-Bentley, Colette and Cubillos-Ruiz, Juan R and Pier, Gerald B and Gilmore, Michael S and Kolter, Roberto and Morales, Diana K}
}
@article {1709821,
	title = {Estimating the rate of severe visual loss (wipe-out) following cataract surgery, a British Ophthalmological Surveillance Unit (BOSU) study},
	journal = {Eye (Lond)},
	volume = {37},
	number = {18},
	year = {2023},
	month = {2023 Dec},
	pages = {3787-3792},
	abstract = {BACKGROUND: A sudden, irreversible reduction in visual acuity ({\textquoteright}wipe-out{\textquoteright}) is a feared complication of cataract surgery. Current literature on wipe-out is limited in quantity and quality, and largely predates modern cataract surgery and imaging techniques. The objectives of our study were to estimate the incidence of wipe-out and to identify potential risk factors.

METHODS: We prospectively collated cases of wipe-out occurring in the UK during a 25-month study period using the British Ophthalmic Surveillance Unit reporting system. A total of 21 potential cases of wipe-out were reported, 5 of which met all inclusion and exclusion criteria.

RESULTS: The estimated incidence of wipe-out during the study period was 0.00000298, or approximately 3 cases per million cataract operations. All cases of wipe-out occurred exclusively in patients with advanced glaucoma (mean deviation -21.0 decibels or worse in the operated eye), with an over-representation of black people (40\%) in our case series. A prior diagnosis of retinal vein occlusion (60\%) and elevated post-operative IOP (40\%) were more common among individuals suffering from wipe-out compared to the general population, suggesting these factors may contribute to the pathogenesis of wipe-out.

CONCLUSIONS: Our study shows that wipe-out is a rare complication, affecting approximately 3 per million undergoing cataract surgery. Patients with advanced glaucoma, black patients, and those with previous retinal vein occlusions may be at greater risk of wipe-out. We hope that the findings of our study will be used to help inform treatment decision-making and the cataract surgery consent process.},
	keywords = {Cataract, Cataract Extraction, Glaucoma, Humans, Retinal Vein Occlusion, Risk Factors},
	issn = {1476-5454},
	doi = {10.1038/s41433-023-02606-9},
	author = {Ramsden, Conor and Shweikh, Yusrah and Kam, Ronald and Bunce, Catey and Foot, Barny and Viswanathan, Ananth}
}
@article {1364531,
	title = {An improved approach to diagnosing and treating conjunctival mucoepidermoid carcinoma},
	journal = {Surv Ophthalmol},
	volume = {57},
	number = {4},
	year = {2012},
	month = {2012 Jul-Aug},
	pages = {337-46},
	abstract = {The current case of conjunctival mucoepidermoid carcinoma offers features that expand the biologic spectrum afforded by this tumor. More focused strategies should be developed for its earlier histopathologic diagnosis and improved management (historical recurrence rate of 85\%). A 63-year-old woman with a history of rheumatoid arthritis and idiopathic sclerosing cholangitis developed scleral thinning, anterior chamber cells and flare, and uveal prolapse. Biopsies of the epibulbar lesion were initially misinterpreted as a squamous cell carcinoma but on review harbored CK7-positive cells and contained rare goblet cells brought out with Alcian blue and mucicarmine staining. Intraocular extension exhibited micro-and macrocysts with minimal goblet cells. Focal CK7 immunopositivity in any epibulbar squamous dysplasia or in invasive carcinoma should lead to suspicion of a mucoepidermoid carcinoma. Behaviorally aggressive or rapidly recurrent epithelial squamous tumors with "inflammatory" features or unusual clinical characteristics should be initially stained at multiple levels for the detection of parsimonious mucus secretion. Surgical options include wide excision and partial sclerectomy with cryotherapy for superficial invasion and/or interferon therapy. Results with radiotherapy and cryotherapy for deep scleral invasion have been unpredictable or unacceptable compared with surgery.},
	keywords = {Biomarkers, Tumor, Carcinoma, Mucoepidermoid, Carcinoma, Squamous Cell, Conjunctival Neoplasms, Diagnosis, Differential, Eye Enucleation, Female, Humans, Middle Aged, Neoplasm Invasiveness},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2011.12.002},
	author = {Rankin, Jessica K and Jakobiec, Frederick A and Zakka, Fouad R and Foster, C Stephen}
}
@article {439676,
	title = {Iris heterochromia and unilateral eyelash hypertrichosis.},
	journal = {JAMA},
	volume = {313},
	number = {19},
	year = {2015},
	month = {2015 May 19},
	pages = {1967-8},
	keywords = {Aged, 80 and over, Amides, Cloprostenol, Eyelashes, Female, Glaucoma, Open-Angle, Humans, Hypertrichosis, Iris Diseases, Pigmentation Disorders},
	issn = {1538-3598},
	doi = {10.1001/jama.2015.1348},
	author = {Rao, Rajesh C and Ballard, Tiffany N S and Chen, Teresa C}
}
@article {1460368,
	title = {ETIOLOGY AND CLINICAL CHARACTERISTICS OF MACULAR EDEMA IN PATIENTS WITH FAMILIAL EXUDATIVE VITREORETINOPATHY},
	journal = {Retina},
	volume = {40},
	number = {7},
	year = {2020},
	month = {2020 Jul},
	pages = {1367-1373},
	abstract = {PURPOSE: To describe the etiology and clinical characteristics of macular edema (ME) in patients with familial exudative vitreoretinopathy. METHODS: Observational, retrospective case series of 30 patients (34 eyes) with ME and familial exudative vitreoretinopathy who underwent spectral-domain optical coherence tomography imaging between 2009 and 2016. Baseline and follow-up optical coherence tomographies were correlated with color fundus photography and fluorescein angiography. RESULTS: The average age was 20.6 years (6.6-68.7). Eighteen eyes exhibited cystoid ME (52.9\%), 14 noncystoid ME (41.2\%), and 2 eyes (5.9\%) with both. Macular edema was foveal in 52.9\% (n = 18). Eighteen of 24 eyes (64.3\%) with an available fluorescein angiography showed leakage from ME. The most common structural feature was posterior hyaloidal organization/contraction (n = 15). Sixteen eyes were treated with topical or intravitreal steroids (n = 6), intravitreal anti-vascular endothelial growth factor (n = 3), or pars plana vitrectomy with membrane stripping (n = 7). There was no difference between mean preoperative and postoperative LogMAR visual acuity (0.63 [20/85] vs. 0.87 [20/148], P = 0.35) after vitrectomy despite a statistical improvement in the mean central foveal thickness (596 mm vs. 303 mm, P = 0.04). CONCLUSION: Macular edema in familial exudative vitreoretinopathy occurs most commonly because of traction. Vitrectomy is effective for relieving tractional forces with anatomical improvement.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002623},
	author = {Rao, Prethy and Lertjirachai, Itsara and Yonekawa, Yoshihiro and Hasbrook, Madeline and Thomas, Benjamin J and Wood, Edward H and Mehta, Neesurg and Mane, Greta and Drenser, Kimberly A and Trese, Michael T and Capone, Antonio}
}
@article {1059806,
	title = {Descemet Membrane Endothelial Keratoplasty After Failed Descemet Stripping Without Endothelial Keratoplasty},
	journal = {Cornea},
	volume = {36},
	number = {7},
	year = {2017},
	month = {2017 Jul},
	pages = {763-766},
	abstract = {PURPOSE: To describe the clinical course, surgical experience, and postoperative outcomes of 3 patients with Fuchs endothelial dystrophy who underwent Descemet membrane endothelial keratoplasty (DMEK) after failed Descemet stripping without endothelial keratoplasty. METHODS: Three patients who underwent DMEK for management of persistent corneal edema after deliberate Descemet stripping in the setting of Fuchs endothelial dystrophy were identified. Patients were examined at day 1, week 1, and months 1, 3, and 6 after DMEK. Visual acuity, central corneal thickness (CCT), and evaluation of central corneal endothelial cell counts were recorded. RESULTS: Two women and one man, aged 56, 72, and 68 years, were included. The time interval between primary Descemet stripping and DMEK ranged from 3.5 to 8 months. Preoperative visual acuities were 20/200, 20/300, and 20/80. Immediately before DMEK, no patients had countable central endothelial cells, and CCTs were 825, 1034, and 878 μm. After DMEK, all patients had improvement in visual acuity to 20/70, 20/20, and 20/20 with CCTs of 529, 504, and 528. The postoperative period in the first case was notable for the immediate development of a pigmented pupillary membrane with posterior synechiae, as well as cystoid macular edema, of uncertain chronicity, noted 1 month postoperatively. The second case also developed posterior synechiae. Two cases completed 6-month endothelial cell counts totaling 2200 and 3114 cells per square millimeter (endothelial cell loss of 13\% and 5.3\%). CONCLUSIONS: DMEK is a reliable procedure to facilitate corneal rehabilitation and visual recovery in the event of poor corneal clearance after Descemet stripping without endothelial keratoplasty.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001214},
	author = {Rao, Rohini and Borkar, Durga S and Colby, Kathryn A and Veldman, Peter B}
}
@article {591231,
	title = {Current trends in the management of thyroid eye disease.},
	journal = {Curr Opin Ophthalmol},
	volume = {26},
	number = {6},
	year = {2015},
	month = {2015 Nov},
	pages = {484-90},
	abstract = {PURPOSE OF REVIEW: The present review summarizes the body of literature concerning the medical and surgical treatment of thyroid eye disease (TED) from 1 January 2014 through 30 March 2015. RECENT FINDINGS: Corticosteroids continue to be the primary medical therapy for TED. Recent research has offered insight into potential differences between oral corticosteroid and intravenous corticosteroid treatment regimens in terms of efficacy and side-effect profiles. Steroid-sparing medications, for example, rituximab and others, are an area of active study. There has been renewed interest in the role of radiation therapy as a nonmedical treatment for TED with some promising data. The use of balanced orbital decompression techniques have become popular, although the data regarding postoperative diplopia are mixed, and {\textquoteright}fat decompression{\textquoteright} offers an alternative or an augmentation to bony decompression. Stereotactic image guidance is a useful adjunct to orbital decompression surgery. SUMMARY: TED continues to be a difficult condition for the patient to cope with and for the clinician to treat, and recent research builds on the present foundation of knowledge and treatments, but unfortunately does not offer paradigm-shifting information at the present time.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000203},
	author = {Rao, Rohini and MacIntosh, Peter W and Yoon, Michael K and Lefebvre, Daniel R}
}
@article {1761951,
	title = {RP2 X-LINKED RETINITIS PIGMENTOSA CARRIER STATE PRESENTING WITH VASCULAR LEAKAGE AND UNILATERAL MACULAR ATROPHY},
	journal = {Retin Cases Brief Rep},
	volume = {17},
	number = {5},
	year = {2023},
	month = {2023 Sep 01},
	pages = {533-537},
	abstract = {PURPOSE: We describe the unusual clinical presentation of a 33-year-old woman subsequently identified as a carrier of RP2-associated X-linked retinitis pigmentosa. METHODS: Case report. RESULTS: A 33-year-old woman without a known family history of retinal disease presented with unilateral reduced visual acuity and central scotoma in the left eye. Examination showed underlying macular atrophy in the left eye and a bilateral tapetal-like reflex. Full-field electroretinogram was abnormal in the left eye but normal in the right eye. Notable findings on wide-field imaging included bilateral peripheral vascular leakage on fluorescein angiography and a bilaterally symmetric radial pattern of hyperfluorescence on fundus autofluorescence. Genetic testing demonstrated a pathogenic variant in the gene RP2 confirming that she was a carrier of X-linked retinitis pigmentosa. CONCLUSION: We describe clinical features of the carrier state of RP2-XLRP and expand potential findings to include peripheral vascular leakage. This case highlights the importance of awareness of the carrier state, particularly if a family history cannot be provided.},
	keywords = {Adult, Atrophy, Carrier State, Female, Fundus Oculi, GTP-Binding Proteins, Humans, Membrane Proteins, Retinal Diseases, Retinitis Pigmentosa},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001239},
	author = {Raparia, Eva and Ballios, Brian G and Place, Emily M and Husain, Deeba and Huckfeldt, Rachel M}
}
@article {694771,
	title = {A Comprehensive Review of Sex Disparities in Symptoms, Pathophysiology, and Epidemiology of Dry Eye Syndrome.},
	journal = {Semin Ophthalmol},
	year = {2016},
	month = {2016 Apr 21},
	abstract = {INTRODUCTION: The etiology, frequency, manifestation, and treatment of dry eye syndrome are commonly influenced by sex and gender. MATERIALS AND METHODS: This study aims to review the differences in epidemiology, pathophysiology, and associated diseases between the sexes. The terms men and male and women and female are used interchangeably throughout the review to refer to biological sex. RESULTS: There are numerous objective and subjective markers of dry eye syndrome but not one diagnostic criterion. There are numerous associated conditions with dry eye syndrome varying from autoimmune to allergic. Large epidemiologic studies reviewed suggest that there does indeed exist a difference between dry eye symptoms between men and women, with women having dry eye signs and reporting dry eye symptoms more often than men. The increased prevalence in women could be correlated to an increased association with certain systemic diseases, specifically autoimmune diseases, and to hormonal variations. Several studies found equivocal data about prevalence of dry eye symptoms between men and women. DISCUSSION: Interpreting studies that investigate epidemiology, pathogenesis, and treatment of dry-eye conditions is complicated by the lack of universally adapted diagnostic criteria and standardized, specific diagnostic tests, and inter-study variability in the definition of dry eye syndrome.},
	issn = {1744-5205},
	doi = {10.3109/08820538.2016.1154168},
	author = {Rapoport, Yuna and Singer, Jason M and Ling, Jeanie D and Gregory, Anthony and Kohanim, Sahar}
}
@article {1603869,
	title = {Chronic ocular complications in lamotrigine vs. trimethoprim-sulfamethoxazole induced Stevens-Johnson syndrome/toxic epidermal necrolysis},
	journal = {Ocul Surf},
	volume = {21},
	year = {2021},
	month = {2021 Jul},
	pages = {16-18},
	abstract = {PURPOSE: The purpose of this study is to compare the severity of chronic ocular complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by lamotrigine (LT) vs. trimethoprim-sulfamethoxazole (TS). METHODS: This retrospective cross-sectional study evaluated all SJS/TEN patients treated within our hospital network from 2008 to 2018. Inclusion criteria included patients with reactions identified as caused by either LT or TS, and patients with at least one ophthalmology follow up in the chronic phase (>=3 months from disease onset). Primary outcome measures included LogMAR best-corrected VA at most recent visit and the presence or absence of severe ocular complications (SOC). Secondary outcome measures included chronic ocular complication severity scores using a modified Sotozono scoring system. RESULTS: Forty-eight eyes of 24 patients were included in the study. The mean duration of follow-up was 39.50\&nbsp;{\textpm}\&nbsp;35.62 vs. 48.17\&nbsp;{\textpm}\&nbsp;33.09 months, respectively (p\&nbsp;=\&nbsp;0.482). The LT group had worse average VA at the most recent visit (LogMAR VA; 0.508 vs. 0.041, p\&nbsp;\&lt;\&nbsp;0.0001) and had a higher prevalence of SOCs (66.7\% vs. 8.3\%, p\&nbsp;=\&nbsp;0.0038). The LT group scored worse on Sotozono chronic complications scores for the cornea (1.875 vs. 0.5, p\&nbsp;=\&nbsp;0.0018), eyelid margin (5.583 vs.3.083, p\&nbsp;=\&nbsp;0.0010), and overall condition (8.500 vs. 4.833, p\&nbsp;=\&nbsp;0.0015). Sub-analyses showed that a moderate or severe acute ocular severity score was a significant predictor of chronic outcomes. CONCLUSIONS: Compared to patients with TS-induced SJS/TEN, patients with LT-induced SJS/TEN developed worse chronic ocular complications on several parameters. Future prospective studies are warranted to provide additional insight into the drug type as a predictor of chronic ocular complications.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.04.009},
	author = {Rashad, Ramy and Shanbhag, Swapna S and Kwan, James and Chodosh, James and Saeed, Saleh and Saeed, Hajirah N}
}
@article {1635648,
	title = {Acute ophthalmic manifestations in Mycoplasma induced rash and mucositis},
	journal = {Ocul Surf},
	volume = {24},
	year = {2022},
	month = {2022 Apr},
	pages = {145-147},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2022.03.004},
	author = {Rashad, Ramy and Elhusseiny, Abdelrahman M and Shanbhag, Swapna S and Chodosh, James and Saeed, Hajirah N}
}
@article {1814351,
	title = {Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study},
	journal = {Br J Ophthalmol},
	year = {2024},
	month = {2024 Mar 15},
	abstract = {PURPOSE: To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures. RESULTS: A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p\&lt;0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460). CONCLUSIONS: Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique.},
	issn = {1468-2079},
	doi = {10.1136/bjo-2023-324076},
	author = {Rashad, Ramy and Kwan, James T and Shanbhag, Swapna S and Ngowyutagon, Panotsom and Saeed, Musa and Tahboub, Mohammad A and Haseeb, Abid and Chodosh, James and Saeed, Hajirah N}
}
@article {313166,
	title = {Epstein-Barr virus-positive polymorphous lymphoplasmacytic infiltrate of the lacrimal glands in a patient with acute lymphoblastic leukemia.},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {892-4},
	keywords = {Antibodies, Viral, B-Lymphocytes, Child, Epstein-Barr Virus Infections, Eye Infections, Viral, Eyelid Diseases, Gene Rearrangement, Herpesvirus 4, Human, Humans, Immunoglobulin Heavy Chains, In Situ Hybridization, Lacrimal Apparatus Diseases, Male, Polymerase Chain Reaction, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Tomography, X-Ray Computed, Tumor Markers, Biological, Viral Load},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.382},
	author = {Rashid, Alia and Lee, N Grace and Jakobiec, Frederick A and Freitag, Suzanne K}
}
@article {1302186,
	title = {Tacrolimus Optic Neuropathy},
	journal = {J Neuroophthalmol},
	volume = {38},
	number = {2},
	year = {2018},
	month = {2018 Jun},
	pages = {160-166},
	abstract = {BACKGROUND: Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss.

METHODS: Case series and review of the literature.

RESULTS: We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy.

CONCLUSIONS: Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000635},
	author = {Rasool, Nailyn and Boudreault, Katherine and Lessell, Simmons and Prasad, Sashank and Cestari, Dean M}
}
@article {1586179,
	title = {Earlier Detection of Glaucoma Progression Using High-Density 3-Dimensional Spectral-Domain OCT Optic Nerve Volume Scans},
	journal = {Ophthalmol Glaucoma},
	volume = {4},
	number = {6},
	year = {2021},
	month = {2021 Nov-Dec},
	pages = {604-616},
	abstract = {PURPOSE: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements. DESIGN: Prospective, longitudinal cohort study. PARTICIPANTS: One hundred twenty-four eyes of 124 patients with open-angle glaucoma. METHODS: Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test-retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods. MAIN OUTCOME MEASURES: Time to glaucoma progression among all 4 methods. RESULTS: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4\%) compared with DP (16.1\%; P \&lt; 0.001) and global RNFL thickness (15.3\%; P \&lt; 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P \&lt; 0.001) or global RNFL thickness (23 months vs. 33 months; P \&lt; 0.001). Among MDB progressing eyes, 46.2\% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ\&nbsp;= 0.095-0.300). CONCLUSIONS: High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.03.010},
	author = {Ratanawongphaibul, Kitiya and Tsikata, Edem and Zemplenyi, Michele and Lee, Hang and Margeta, Milica A and Ondeck, Courtney L and Kim, Janice and Pan, Billy X and Petrakos, Paul and Coleman, Anne L and Yu, Fei and de Boer, Johannes F and Chen, Teresa C}
}
@article {303976,
	title = {Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration.},
	journal = {Hum Mol Genet},
	volume = {23},
	number = {21},
	year = {2014},
	month = {2014 Nov 1},
	pages = {5827-37},
	abstract = {Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch{\textquoteright}s membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 {\texttimes} 10(-5)). Thus, it appears that rare and common variants in a single gene-FBN2-can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch{\textquoteright}s membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddu276},
	author = {Ratnapriya, Rinki and Zhan, Xiaowei and Fariss, Robert N and Branham, Kari E and Zipprer, David and Chakarova, Christina F and Sergeev, Yuri V and Campos, Maria M and Othman, Mohammad and Friedman, James S and Maminishkis, Arvydas and Waseem, Naushin H and Brooks, Matthew and Rajasimha, Harsha K and Edwards, Albert O and Lotery, Andrew and Klein, Barbara E and Truitt, Barbara J and Li, Bingshan and Schaumberg, Debra A and Morgan, Denise J and Morrison, Margaux A and Souied, Eric and Tsironi, Evangelia E and Grassmann, Felix and Fishman, Gerald A and Silvestri, Giuliana and Scholl, Hendrik P N and Kim, Ivana K and Ramke, Jacqueline and Tuo, Jingsheng and Merriam, Joanna E and Merriam, John C and Park, Kyu Hyung and Olson, Lana M and Farrer, Lindsay A and Johnson, Matthew P and Peachey, Neal S and Lathrop, Mark and Baron, Robert V and Igo, Robert P and Klein, Ronald and Hagstrom, Stephanie A and Kamatani, Yoichiro and Martin, Tammy M and Jiang, Yingda and Conley, Yvette and Sahel, Jose-Alan and Zack, Donald J and Chan, Chi-Chao and Pericak-Vance, Margaret A and Jacobson, Samuel G and Gorin, Michael B and Klein, Michael L and Allikmets, Rando and Iyengar, Sudha K and Weber, Bernhard H and Haines, Jonathan L and L{\'e}veillard, Thierry and Deangelis, Margaret M and Stambolian, Dwight and Weeks, Daniel E and Bhattacharya, Shomi S and Chew, Emily Y and Heckenlively, John R and Abecasis, Gon{\c c}alo R and Swaroop, Anand}
}
@article {1814431,
	title = {Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study},
	journal = {Diabetologia},
	volume = {67},
	number = {5},
	year = {2024},
	month = {2024 May},
	pages = {928-939},
	abstract = {AIMS/HYPOTHESIS: As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset. METHODS: The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4\% [39-47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings. RESULTS: In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised β=-0.096; p\&lt;0.001 for HOMA2-IR) and myoid zone (MZ; β=-0.096; p\&lt;0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (β=0.090; p\&lt;0.001 for eGDR) and MZ (β=0.133; p\&lt;0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis. CONCLUSIONS/INTERPRETATION: An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.},
	keywords = {Adult, Cross-Sectional Studies, Diabetic Retinopathy, Glucose, Glucose Intolerance, Humans, Insulin Resistance, Prediabetic State, Retina},
	issn = {1432-0428},
	doi = {10.1007/s00125-024-06093-9},
	author = {Rauscher, Franziska G and Tobias Elze and Francke, Mike and Martinez-Perez, M Elena and Li, Yangjiani and Wirkner, Kerstin and T{\"o}njes, Anke and Engel, Christoph and Thiery, Joachim and Bl{\"u}her, Matthias and Stumvoll, Michael and Kirsten, Toralf and Loeffler, Markus and Ebert, Thomas and Wang, Mengyu}
}
@article {1586153,
	title = {Primary central nervous system lymphoma - ocular variant: an interdisciplinary review on management},
	journal = {Surv Ophthalmol},
	volume = {66},
	number = {6},
	year = {2021},
	month = {2021 Nov-Dec},
	pages = {1009-1020},
	abstract = {Primary central nervous system lymphoma-ophthalmic variant (PCNSL-O) is an ocular subset of PCNSL predominantly involving subretinal pigment epithelium space, retina, and vitreous. The ophthalmic manifestations can precede, occur simultaneously, or follow other compartments of the CNS. Clinical trials have resulted in a significantly improved outcome in PCNSL patients over the past 2 decades, with a higher proportion of patients receiving frontline high dose methotrexate-based polychemotherapy regimens with curative intent; however, the current management of PCNSL-O remains controversial owing to lack of prospective data. The goals of PCNSL-O treatment are both to achieve local (ocular) control and to prevent tumor-specific mortality from further CNS involvement. Despite achieving high rates of ocular control with intravitreal agents like methotrexate and rituximab, the overall survival is poor, as 65-85\% of patients eventually succumb to CNS disease. Few studies define the role of systemic chemotherapy with/without local treatment as a first line induction treatment for PCNSL-O considering limiting factors such as ocular penetration of systemically administered drugs and treatment related neurotoxicity. Also, the role of adjuvant treatment for PCNSL-O to prevent CNS progression and to improve overall survival is unknown. In this systematic review of the literature, we analyze treatment outcomes of various regimens (local, systemic, and combination) in terms of local control, CNS progression, and overall survival.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2021.03.004},
	author = {Raval, Vishal and Binkley, Elaine and Aronow, Mary E and Valenzuela, Juan and Peereboom, David M and Singh, Arun D}
}
@article {1319478,
	title = {Angiographic Findings in the Tolosa-Hunt Syndrome and Resolution after Corticosteroid Treatment},
	journal = {Neuroophthalmology},
	volume = {42},
	number = {3},
	year = {2018},
	month = {2018 Jun},
	pages = {159-163},
	abstract = {The Tolosa-Hunt syndrome is a rare clinical condition characterized by painful opthalmoparesis associated with idiopathic granulomatous inflammation of the orbital apex and cavernous sinus. Historically, this condition was thought to result from arteritic changes in the internal carotid artery and cavernous sinus. Modern digital angiographic techniques were unavailable when THS was initially described, and few reports exist on its high-resolution angiographic findings. Painful ophthalmoparesis, especially of the oculomotor nerve, warrants vascular imaging because of the concern for an underlying aneurysm. Here, we describe angiographic findings of THS which may be useful for clinicians when encountering patients presenting with painful ophthalmoplegia.},
	issn = {0165-8107},
	doi = {10.1080/01658107.2017.1365268},
	author = {Ravindran, Krishnan and Schmalz, Philip and Torun, Nurhan and Ronthal, Michael and Chang, Yu-Ming and Ajith J Thomas}
}
@article {1806646,
	title = {Changes in wider field swept-source OCT angiography vascular metrics with anti-vascular endothelial growth factor therapy in central retinal vein occlusion},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	year = {2024},
	month = {2024 Feb 20},
	abstract = {PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO\&nbsp;from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369\&nbsp;{\textmu}m (305-531) to 267\&nbsp;{\textmu}m (243-300, p \&lt; 0.001). VD and VSD parameters in 12 {\texttimes} 12\&nbsp;mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 {\texttimes} 12\&nbsp;mm images (p \&lt; 0.05). Notably, the reductions in VSD and VD on 12 {\texttimes} 12\&nbsp;mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.},
	issn = {1435-702X},
	doi = {10.1007/s00417-024-06410-3},
	author = {Razavi, Peyman and Baldwin, Grace and Garg, Itika and Velazquez, Luis Martinez and Garcia, Mauricio and Gan, Jenny and Choi, Hanna and Zeng, Rebecca and Vingopoulos, Filippos and Husain, Deeba and Kim, Leo A and Patel, Nimesh A and Miller, John B}
}
@article {1748391,
	title = {Heads-Up Three-Dimensional Viewing Systems in Vitreoretinal Surgery: An Updated Perspective},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {2539-2552},
	abstract = {Three-Dimensional (3D) heads-up visualization systems have significantly advanced vitreoretinal surgery, providing enhanced detail and improved ergonomics. This review discusses the application of 3D systems in vitreoretinal surgery, their use in various procedures, their combination with other imaging modalities, and the role of this technology in medical education and telementoring. Furthermore, the review highlights the benefits of 3D systems, such as improved ergonomics, reduced phototoxicity, enhanced depth of field, and the use of color filters. Potential challenges, including the learning curve and additional costs, are also addressed. The review concludes by exploring promising future applications, including teleophthalmology for remote assistance and specialist availability expansion, virtual reality integration for global clinical education, and the combination of remotely robotic-guided surgery with artificial intelligence for precise, efficient surgical procedures. This comprehensive review offers insights into the current state and future potential of 3D heads-up visualization systems in vitreoretinal surgery, underscoring the transformative impact of this technology on ophthalmology.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S424229},
	author = {Razavi, Peyman and Cakir, Bertan and Baldwin, Grace and D{\textquoteright}Amico, Donald J and Miller, John B}
}
@article {1490449,
	title = {Pathophysiology and management of glaucoma and ocular hypertension related to trauma},
	journal = {Surv Ophthalmol},
	volume = {65},
	number = {5},
	year = {2020},
	month = {2020 Sep - Oct},
	pages = {530-547},
	abstract = {Ocular trauma is a significant cause of blindness worldwide, particularly if associated with glaucoma. Direct damage from blunt or penetrating trauma, bleeding, inflammation, lens-related problems, orbital and brain vascular pathologies related to trauma, and chemical injuries may increase intraocular pressure and lead to traumatic glaucoma. Treatment may be as simple as eliminating the underlying cause in some conditions or management can be challenging, depending on the mechanism of damage. If proper management is not undertaken, visual outcomes can be poor. We discuss a broad spectrum of trauma-related mechanisms of intraocular pressure elevation, as well as their management.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2020.02.003},
	author = {Razeghinejad, Reza and Lin, Michael M and Lee, Daniel and Katz, L Jay and Myers, Jonathan S}
}
@article {882976,
	title = {Long-term surgical outcomes of retinal detachment in patients with Stickler syndrome.},
	journal = {Clin Ophthalmol},
	volume = {10},
	year = {2016},
	month = {2016},
	pages = {1531-4},
	abstract = {PURPOSE: The aim of the study was to present the long-term anatomical and visual outcomes of retinal detachment repair in patients with Stickler syndrome. PATIENTS AND METHODS: This study is a retrospective, interventional, consecutive case series of patients with Stickler syndrome undergoing retinal reattachment surgery from 2009 to 2014 at the Associated Retinal Consultants, William Beaumont Hospital. RESULTS: Sixteen eyes from 13 patients were identified. Patients underwent a mean of 3.1 surgical interventions (range: 1-13) with a mean postoperative follow-up of 94 months (range: 5-313 months). Twelve eyes (75\%) developed proliferative vitreoretinopathy. Retinal reattachment was achieved in 100\% of eyes, with ten eyes (63\%) requiring silicone oil tamponade at final follow-up. Mean preoperative visual acuity (VA) was 20/914, which improved to 20/796 at final follow-up (P=0.81). There was a significant correlation between presenting and final VA (P\&lt;0.001), and patients with poorer presenting VA were more likely to require silicone oil tamponade at final follow-up (P=0.04). CONCLUSION: Repair of retinal detachment in patients with Stickler syndrome often requires multiple surgeries, and visual outcomes are variable. Presenting VA is significantly predictive of long-term VA outcomes.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S111526},
	author = {Reddy, Devasis N and Yonekawa, Yoshihiro and Thomas, Benjamin J and Nudleman, Eric D and Williams, George A}
}
@article {504096,
	title = {Diagnostic Sensitivity of Indocyanine Green Angiography for Birdshot Chorioretinopathy.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {7},
	year = {2015},
	month = {2015 Jul 1},
	pages = {840-3},
	abstract = {IMPORTANCE: To describe a cohort of patients with birdshot chorioretinopathy who did not manifest birdshot lesions on clinical examination but had retinal vasculitis, low-grade to moderate vitritis, and hypocyanescent lesions on indocyanine green angiography (ICGA). OBSERVATIONS: Case series of 3 patients with mild to moderate vitritis and retinal vasculitis without definite birdshot lesions on clinical examination evaluated from January 2007 to December 2014 at 4 academic ophthalmology centers. All patients{\textquoteright} results were positive for human leukocyte antigen-A29. All cases had hypocyanescent lesions visible on ICGA but not detectable on fluorescein angiography. CONCLUSIONS AND RELEVANCE: Patients with retinal vasculitis and low-grade vitritis with or without macular edema may have birdshot chorioretinopathy evident on ICGA before lesions are visible on clinical examination or fluorescein angiography. Expanding birdshot chorioretinopathy diagnostic criteria to include the presence of hypocyanescent lesions on ICGA could improve the sensitivity of diagnosis.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.0822},
	author = {Reddy, Ashvini K and Gonzalez, Marco A and Henry, Christopher R and Yeh, Steven and Sobrin, Lucia and Albini, Thomas A}
}
@article {1549009,
	title = {Neuro-ophthalmic manifestations of Susac syndrome},
	journal = {Curr Opin Ophthalmol},
	volume = {31},
	number = {6},
	year = {2020},
	month = {2020 Nov},
	pages = {495-502},
	abstract = {PURPOSE OF REVIEW: This review discusses general features and organ-specific presentations of Susac syndrome as well as diagnosis and treatment.

RECENT FINDINGS: Latest literature regarding demographics, new diagnostic modalities such as optical coherence tomography and treatment options for Susac syndrome are discussed in detail in this review, summarizing the most recent updated information.

SUMMARY: Susac syndrome is a rare, underdiagnosed, and often misdiagnosed disease that can lead to severe complications such as deafness, vision loss, dementia, and death. It involves the central nervous system and may mimic other neurological and neuro-ophthalmological diseases.},
	keywords = {Brain, Humans, Susac Syndrome, Tomography, Optical Coherence, Vision Disorders},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000713},
	author = {Redler, Yael and Chwalisz, Bart K}
}
@article {1549001,
	title = {Rodent Models of Optic Neuritis},
	journal = {Front Neurol},
	volume = {11},
	year = {2020},
	month = {2020},
	pages = {580951},
	abstract = {Optic neuritis (ON) is an inflammatory attack of the optic nerve that leads to visual disability. It is the most common optic neuropathy affecting healthy young adults, most commonly women aged 20-45 years. It can be idiopathic and monophasic or as part of a neurologic disease such as multiple sclerosis with recurrence and cumulative damage. Currently, there is no therapy to repair the damage from optic neuritis. Animal models are an essential tool for the understanding of the pathogenesis of optic neuritis and for the development of potential treatment strategies. Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental rodent model for human autoimmune inflammatory demyelinating diseases of the central nervous system (CNS). In this review, we discuss the latest rodent models regarding optic neuritis, focusing on EAE model, and on its recent achievements and developments.},
	issn = {1664-2295},
	doi = {10.3389/fneur.2020.580951},
	author = {Redler, Yael and Michael Levy}
}
@article {1667692,
	title = {Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice},
	journal = {Nat Med},
	volume = {29},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {412-421},
	abstract = {Dominant missense pathogenic variants in cardiac myosin heavy chain cause hypertrophic cardiomyopathy (HCM), a currently incurable disorder that increases risk for stroke, heart failure and sudden cardiac death. In this study, we assessed two different genetic therapies-an adenine base editor (ABE8e) and a potent Cas9 nuclease delivered by AAV9-to prevent disease in mice carrying the heterozygous HCM pathogenic variant myosin R403Q. One dose of dual-AAV9 vectors, each carrying one half of RNA-guided ABE8e, corrected the pathogenic variant in >=70\% of ventricular cardiomyocytes and maintained durable, normal cardiac structure and function. An additional dose provided more editing in the atria but also increased bystander editing. AAV9 delivery of RNA-guided Cas9 nuclease effectively inactivated the pathogenic allele, albeit with dose-dependent toxicities, necessitating a narrow therapeutic window to maintain health. These preclinical studies demonstrate considerable potential for single-dose genetic therapies to correct or silence pathogenic variants and prevent the development of HCM.},
	keywords = {Animals, Cardiomyopathy, Hypertrophic, Gene Editing, Mice, Mutation, Missense, Myocytes, Cardiac, RNA},
	issn = {1546-170X},
	doi = {10.1038/s41591-022-02190-7},
	author = {Reichart, Daniel and Newby, Gregory A and Wakimoto, Hiroko and Lun, Mingyue and Gorham, Joshua M and Curran, Justin J and Raguram, Aditya and DeLaughter, Daniel M and Conner, David A and Marsiglia, J{\'u}lia D C and Kohli, Sajeev and Chmatal, Lukas and Page, David C and Zabaleta, Nerea and Vandenberghe, Luk and Liu, David R and Seidman, Jonathan G and Seidman, Christine}
}
@article {1732636,
	title = {Metabolomic Profiling of Long-Chain Polyunsaturated Fatty Acid Oxidation in Adults with Retinal Vein Occlusion: A Case-Control Study},
	journal = {Am J Clin Nutr},
	volume = {118},
	number = {3},
	year = {2023},
	month = {2023 Sep},
	pages = {579-590},
	abstract = {BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFAs) and their metabolites are closely related to neovascular eye diseases. However, the clinical significance of their oxylipins in retinal vein occlusion (RVO) remains inconclusive. OBJECTIVES: This case-control study aimed to explore metabolomic profiles of LCPUFA oxidation in RVO and to identify potential indicators for diagnosis and pathologic progression. METHODS: The plasma concentrations of ω-3 (n-3) and ω-6 (n-6) LCPUFA and their oxylipins in 44 adults with RVO and 36 normal controls were analyzed using ultraperformance liquid chromatography tandem mass spectrometry. Univariate analysis combined with principal component and orthogonal projections to latent structure discriminant analysis was used to screen differential metabolites. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of 5-oxo-eicosatetraenoic acids (ETE) on angiogenesis ex vivo. Tubule formation and wound healing assays were performed to verify its effects on human retinal microvascular endothelial cell functions. RESULTS: Higher ω-6 and lower ω-3 LCPUFA plasma concentrations were measured in the adults with RVO compared with control (odds ratio [OR]: 2.34; 95\% confidence interval [CI]: 1.42, 3.86; P \&lt; 0.001; OR: 0.28; 95\% CI: 0.15, 0.51; P \&lt; 0.001). Metabolomic analysis revealed 20 LCPUFA and their oxylipins dysregulated in RVO, including increased arachidonic acid (ω-6, OR: 1.85; 95\% CI: 1.18, 2.90; P \&lt; 0.001) and its lipoxygenase product 5-oxo-ETE (OR: 11.76; 95\% CI: 3.73, 37.11; P \&lt; 0.001), as well as decreased docosahexaenoic acid (ω-3, OR: 0.13; 95\% CI: 0.05, 0.33; P \&lt; 0.001). Interestingly, 5-oxo-ETE was downregulated in ischemic compared with nonischemic central RVO. Exogenous 5-oxo-ETE attenuated aortic ring and choroidal explant sprouting and inhibited tubule formation and migration of human retinal microvascular endothelial cells in a dose-dependent manner, possibly via suppressing the vascular endothelial growth factor signaling pathway. CONCLUSIONS: The plasma concentrations of ω-6 and ω-3 LCPUFA and their oxylipins were associated with RVO. The ω-6 LCPUFA-derived metabolite 5-oxo-ETE was a potential marker of RVO development and progression.},
	keywords = {Adult, Case-Control Studies, Endothelial Cells, Fatty Acids, Omega-3, Humans, Oxylipins, Retinal Vein Occlusion, Vascular Endothelial Growth Factor A},
	issn = {1938-3207},
	doi = {10.1016/j.ajcnut.2023.07.006},
	author = {Ren, Jiangbo and Ren, Anli and Huang, Zhengrong and Deng, Xizhi and Jiang, Ziyu and Xue, Yanni and Fu, Zhongjie and Smith, Lois E H and Ke, Min and Gong, Yan}
}
@article {1732596,
	title = {Low-Dose 0.01\% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {8},
	year = {2023},
	month = {2023 Aug 01},
	pages = {756-765},
	abstract = {IMPORTANCE: Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia. OBJECTIVE: To compare atropine, 0.01\%, eye drops with placebo for slowing myopia progression in US children. DESIGN, SETTING, AND PARTICIPANTS: This was a randomized placebo-controlled, double-masked, clinical trial conducted from June 2018 to September 2022. Children aged 5 to 12 years were recruited from 12 community- and institution-based practices in the US. Participating children had low to moderate bilateral myopia (-1.00 diopters [D] to -6.00 D spherical equivalent refractive error [SER]). INTERVENTION: Eligible children were randomly assigned 2:1 to 1 eye drop of atropine, 0.01\%, nightly or 1 drop of placebo. Treatment was for 24 months followed by 6 months of observation. MAIN OUTCOME AND MEASURES: Automated cycloplegic refraction was performed by masked examiners. The primary outcome was change in SER (mean of both eyes) from baseline to 24 months (receiving treatment); other outcomes included change in SER from baseline to 30 months (not receiving treatment) and change in axial length at both time points. Differences were calculated as atropine minus placebo. RESULTS: A total of 187 children (mean [SD] age, 10.1 [1.8] years; age range, 5.1-12.9 years; 101 female [54\%]; 34 Black [18\%], 20 East Asian [11\%], 30 Hispanic or Latino [16\%], 11 multiracial [6\%], 6 West/South Asian [3\%], 86 White [46\%]) were included in the study. A total of 125 children (67\%) received atropine, 0.01\%, and 62 children (33\%) received placebo. Follow-up was completed at 24 months by 119 of 125 children (95\%) in the atropine group and 58 of 62 children (94\%) in the placebo group. At 30 months, follow-up was completed by 118 of 125 children (94\%) in the atropine group and 57 of 62 children (92\%) in the placebo group. At the 24-month primary outcome visit, the adjusted mean (95\% CI) change in SER from baseline was -0.82 (-0.96 to -0.68) D and -0.80 (-0.98 to -0.62) D in the atropine and placebo groups, respectively (adjusted difference = -0.02 D; 95\% CI, -0.19 to +0.15 D; P = .83). At 30 months (6 months not receiving treatment), the adjusted difference in mean SER change from baseline was -0.04 D (95\% CI, -0.25 to +0.17 D). Adjusted mean (95\% CI) changes in axial length from baseline to 24 months were 0.44 (0.39-0.50) mm and 0.45 (0.37-0.52) mm in the atropine and placebo groups, respectively (adjusted difference = -0.002 mm; 95\% CI, -0.106 to 0.102 mm). Adjusted difference in mean axial elongation from baseline to 30 months was +0.009 mm (95\% CI, -0.115 to 0.134 mm). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of school-aged children in the US with low to moderate myopia, atropine, 0.01\%, eye drops administered nightly when compared with placebo did not slow myopia progression or axial elongation. These results do not support use of atropine, 0.01\%, eye drops to slow myopia progression or axial elongation in US children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03334253.},
	keywords = {Atropine, Child, Child, Preschool, Disease Progression, Female, Humans, Myopia, Ophthalmic Solutions, Refraction, Ocular, Vision Tests},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.2855},
	author = {Repka, Michael X and Weise, Katherine K and Chandler, Danielle L and Wu, Rui and Melia, B Michele and Manny, Ruth E and Kehler, Lori Ann F and Jordan, Catherine O and Raghuram, Aparna and Summers, Allison I and Lee, Katherine A and Petersen, David B and Erzurum, S A and Pang, Yi and Lenhart, Phoebe D and Ticho, Benjamin H and Beck, Roy W and Kraker, Raymond T and Holmes, Jonathan M and Cotter, Susan A and Pediatric Eye Disease Investigator Group}
}
@article {1478325,
	title = {Clinical and radiographic features of hydrolyzed MIRAgel scleral buckles: A comparative analysis},
	journal = {Clin Imaging},
	volume = {60},
	number = {1},
	year = {2019},
	month = {2019 Dec 06},
	pages = {10-15},
	abstract = {The MIRAgel (hydrogel) scleral buckle, introduced in the 1980s, was a novel material to repair retinal detachments. It was later discontinued due to the frequency of long-term complications related to buckle hydrolysis and expansion. These complications included pain, limited extraocular motility, and more serious complications such as infection or scleral perforation, which ultimately necessitated surgical extraction as late as 20-30\&nbsp;years after placement. Prompt and proper diagnosis and treatment is often delayed as these buckle-associated complications frequently mimic other orbital pathologies such as tumors or infections. The hydrolyzed MIRAgel buckle exhibits distinct radiographic features that are helpful in arriving at the correct diagnosis, particularly in cases of ambiguous clinical presentation or history. Here, we expand on the previously described radiographic features of hydrolyzed MIRAgel and compare them to features of common, mimicking orbital pathology.},
	issn = {1873-4499},
	doi = {10.1016/j.clinimag.2019.11.017},
	author = {Reshef, Edith R and Habib, Larissa A and Rao, Rohini and Modjtahedi, Bobeck S and Eliott, Dean and Freitag, Suzanne K and Reinshagen, Katherine L and Lee, Nahyoung G}
}
@article {1318873,
	title = {Histopathologic Findings of Linear Scleroderma Displaying Focal Trichiasis Secondary to Tarsal Thinning},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {4},
	year = {2018},
	month = {2018 Jul/Aug},
	pages = {e124-e127},
	abstract = {Linear scleroderma en coup de sabre with ophthalmic findings has been previously described in the literature on numerous occasions. A 57-year-old woman presented with focal trichiasis secondary to tarsal thinning, adjacent to a linear brow and forehead deformity consistent with linear scleroderma en coup de sabre. Cases of linear scleroderma en coup de sabre involving the eyelids have been reported, most often with madarosis, ptosis, or skin atrophy; however, to the authors{\textquoteright} knowledge, this is the first reported case of linear scleroderma associated with trichiasis and involvement of the deeper eyelid tissues, particularly the tarsus.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001140},
	author = {Reshef, Edith R and Wolkow, Natalie and Jakobiec, Frederick A and Yoon, Michael K}
}
@article {1635626,
	title = {Orbital Inflammation Following COVID-19 Vaccination},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {3},
	year = {2022},
	month = {2022 May-Jun 01},
	pages = {e67-e70},
	abstract = {Three patients presented with periorbital swelling, pain with extraocular movements, and binocular diplopia 1-4 days after receiving an mRNA Coronavirus Infectious Disease-19 (COVID-19) vaccine (BNT162b2, Pfizer/BioNTech; mRNA-1273, Moderna). All patients had a normal afferent function, unilateral limitation of extraocular motility, proptosis, and periorbital inflammation. Neuroimaging of the orbits with contrast revealed inflammation and enlargement of extraocular muscles in 2 cases and the lacrimal gland in 1 case. In all 3 cases, an extensive infectious and inflammatory laboratory work-up was unremarkable and signs and symptoms of orbital inflammation rapidly improved to complete resolution after treatment with high-dose oral prednisone. This is the first reported series of orbital inflammation occurring shortly after administration of the COVID-19 vaccine. Clinicians may consider an inflammatory postvaccine etiology as an alternative to presumed idiopathic diagnosis in such cases.},
	keywords = {BNT162 Vaccine, Communicable Diseases, COVID-19, COVID-19 Vaccines, Humans, Inflammation, Vaccination},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002161},
	author = {Reshef, Edith R and Freitag, Suzanne K and Lee, Nahyoung Grace}
}
@article {1417573,
	title = {A Neurologic Examination for Anesthesiologists: Assessing Arousal Level during Induction, Maintenance, and Emergence},
	journal = {Anesthesiology},
	volume = {130},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {462-471},
	abstract = {Anesthetics have profound effects on the brain and central nervous system. Vital signs, along with the electroencephalogram and electroencephalogram-based indices, are commonly used to assess the brain states of patients receiving general anesthesia and sedation. Important information about the patient{\textquoteright}s arousal state during general anesthesia can also be obtained through use of the neurologic examination. This article reviews the main components of the neurologic examination focusing primarily on the brainstem examination. It details the components of the brainstem examination that are most relevant for patient management during induction, maintenance, and emergence from general anesthesia. The examination is easy to apply and provides important complementary information about the patient{\textquoteright}s arousal level that cannot be discerned from vital signs and electroencephalogram measures.},
	issn = {1528-1175},
	doi = {10.1097/ALN.0000000000002559},
	author = {Reshef, Edith R and Schiff, Nicholas D and Brown, Emery N}
}
@article {1667700,
	title = {Reduction in Extraocular Muscle Cross-sectional Area and Correlation With Extraocular Motility and Diplopia Following Teprotumumab for Thyroid Eye Disease},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {39},
	number = {5},
	year = {2023},
	month = {2023 Sep-Oct 01},
	pages = {433-439},
	abstract = {PURPOSE: To quantify changes in extraocular muscle (EOM) cross-sectional areas (CSA) on orbital imaging in patients with thyroid eye disease before and after teprotumumab treatment, and assess for correlation with clinical outcomes. METHODS: This retrospective study included thyroid eye disease patients treated with teprotumumab who had pre- and post-treatment CT imaging. Reformatted oblique coronal images were created for each orbit in a plane perpendicular to the optic nerve. EOM CSA measurements were performed by 2 radiographic reviewers and averaged. Primary outcomes included change in ratio of total EOM to orbit CSA, and of each individual muscle group to orbit CSA, before and after treatment. Secondary outcomes included subanalysis based on age (>=40, \&lt;40 years) and Clinical Activity Score (CAS) (>=4, \&lt;4), and comparison with clinical outcomes including CAS, Hertel exophthalmometry, Gorman diplopia score, and extraocular motility. RESULTS: Forty-eight orbits of 24 patients (16 female, mean age 57.9 years) were included. There was a significant reduction in the total EOM to orbit CSA ratio ( p \&lt; 0.01) and for each individual rectus muscle to orbit CSA ratio ( p \&lt; 0.01 for all groups). Total EOM to orbit CSA ratios were reduced for 21 patients (87.5\%); this was statistically significant in 13 patients (54.2\%). There was significant improvement in CAS, proptosis, diplopia, and EOM motility ( p \&lt; 0.01 for all categories). There was a significant correlation between reduction of EOM CSA, and reduction of diplopia ( p \&lt; 0.01) and EOM motility ( p \&lt; 0.01). CONCLUSIONS: EOM CSA is significantly reduced following treatment with teprotumumab, and correlates with clinical findings including improvement in extraocular motility and diplopia.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002337},
	author = {Reshef, Edith R and Marsiglia, Marcela and Bouhadjer, Karim and Chiou, Carolina A and O{\textquoteright}Brien-Coon, Devin and Reinshagen, Katherine L and Freitag, Suzanne K}
}
@article {1586182,
	title = {The Endoscopic Transnasal Approach to Orbital Tumors: A Review},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {232-240},
	abstract = {Historically, surgical access to orbital tumors has required a transcutaneous, transconjunctival or transcranial approach. Resection of orbital tumors is notoriously challenging due to the surrounding dense network of critical structures in a confined bony cavity. Advances in endoscopic endonasal surgery, initially used for sinonasal and skull base conditions, have allowed for expansion of its applications beyond the sinorbital interface. In the past decade, the evolution of techniques has enabled a purely endoscopic, minimally invasive approach to medially located orbital pathology with good outcomes. With experience and multidisciplinary collaboration between orbit and rhinologic surgeons, this has expanded to allow for a safe and effective transnasal approach to nearly all regions of the orbit with or without assistance from the orbital side. This review summarizes the relevant anatomy, variations of surgical approaches, and literature regarding outcomes of the endoscopic endonasal approach to orbital tumors.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1890794},
	author = {Reshef, Edith R and Bleier, Benjamin S and Freitag, Suzanne K}
}
@article {1677701,
	title = {Partial Recovery of Amblyopia After Fellow Eye Ischemic Optic Neuropathy},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {1},
	year = {2023},
	month = {2023 Mar 01},
	pages = {76-81},
	abstract = {BACKGROUND: Recovery from amblyopia in adulthood after fellow eye (FE) vision loss is a well-known phenomenon. Incidence of recovery varies widely following different FE pathologies, and the rate of recovery after FE ischemic optic neuropathy (ION) has not been examined. We aimed to determine the frequency and degree of improvement in amblyopic eye (AE) visual function after ION in the FE. METHODS: We performed a retrospective chart review of patients between 2007 and 2021 confirmed to have amblyopia and ischemic optic neuropathy in different eyes. Patients with unstable ocular pathology potentially limiting vision were excluded. We compared the best-corrected visual acuity (VA) in each eye before and after FE ION over time. For patients with available data, we examined change in perimetric performance over time. RESULTS: Among the 12 patients who met the inclusion criteria (mean age 67 {\textpm} 8 years), 9 (75\%) improved >=1 line and 2 (17\%) improved >=3 lines. The median time from ION symptom onset to maximal improvement was 6 months (range: 2-101 months). Reliable perimetric data were available for 6 patients. Mean sensitivity improved in the AE for all patients, with mean improvement of 1.9 {\textpm} 1.1 dB. There was no correspondence between foci of ION-related field loss and gains in field sensitivity in the AE. CONCLUSIONS: A high proportion of patients with amblyopia and contralateral ION experience improvement in AEVA. Modest gains in perimetric sensitivity in the AE may accompany FE ION. These findings support the view that residual plasticity in the adult visual cortex can be tapped to support functional improvement in amblyopia.},
	keywords = {Adult, Aged, Amblyopia, Eye, Humans, Middle Aged, Optic Neuropathy, Ischemic, Retrospective Studies, Visual Acuity},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001646},
	author = {Resnick, Hannah H and Bear, Mark F and Gaier, Eric D}
}
@article {1789181,
	title = {FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain},
	journal = {Am J Ophthalmol},
	year = {2023},
	month = {2023 Dec 13},
	abstract = {PURPOSE: To assess the therapeutic effect of tinted lenses (FL-41) on photophobia and light-evoked brain activity using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular surface pain. DESIGN: Prospective case series. METHODS: 25 subjects from the Miami Veterans Affairs (VA) eye clinic were recruited based on the presence of chronic ocular pain, dry eye symptoms, and photophobia. Using a 3T MRI scanner, subjects underwent two fMRI scans using an event-related design based on light stimuli: one scan while wearing FL-41 lenses and one without. Unpleasantness ratings evoked by the light stimuli were collected after each scan. RESULTS: With FL-41 lenses, subjects reported decreased (n=19), maintained (n=2), or increased (n=4) light-evoked unpleasantness ratings. Group analysis at baseline (no lens) revealed significant light evoked responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral insula, bilateral frontal pole, visual, precuneus, paracingulate, and anterior cingulate cortices (ACC) as well as cerebellar vermis, bilateral cerebellar hemispheric lobule VI, and bilateral cerebellar crus I and II. With FL-41 lenses, light-evoked responses were significantly decreased in bilateral S1, bilateral S2, bilateral insular, right temporal pole, precuneus, ACC, and paracingulate cortices as well as bilateral cerebellar hemispheric lobule VI. CONCLUSION: FL-41 lenses modulated photophobia symptoms in some individuals with chronic ocular pain. In conjunction, FL-41 lenses decreased activation in cortical areas involved in processing affective and sensory-discriminative dimensions of pain. Further research into these relationships will advance the ability to provide precision therapy for individuals with ocular pain.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.12.004},
	author = {Reyes, Nicholas and Huang, Jaxon J and Choudhury, Anjalee and Pondelis, Nicholas and Locatelli, Elyana V T and Hollinger, Ruby and Felix, Elizabeth R and Pattany, Pradip M and Galor, Anat and Moulton, Eric A}
}
@article {314181,
	title = {Omega-3 supplementation combined with anti-vascular endothelial growth factor lowers vitreal levels of vascular endothelial growth factor in wet age-related macular degeneration.},
	journal = {Am J Ophthalmol},
	volume = {158},
	number = {5},
	year = {2014},
	month = {2014 Nov},
	pages = {1071-1078.e1},
	abstract = {PURPOSE: To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A (VEGF-A) levels in patients with exudative age-related macular degeneration (wet AMD) receiving intravitreal anti-VEGF treatment. DESIGN: Prospective, randomized, open-label, single-center, clinical trial, consecutive interventional case series. METHODS: The study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole. Twenty wet AMD patients being treated with anti-VEGF were randomized to daily supplementation of antioxidants, zinc, and carotenoids with omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid; group 1, n\&nbsp;= 10) or without omega-3 fatty acids (group 2, n\&nbsp;= 10). They were compared with an anti-VEGF treatment-na{\"\i}ve wet AMD group (group 3, n\&nbsp;= 10) and an epiretinal membrane or macular hole group (group 4, n\&nbsp;= 10). Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness. Patients with new submacular hemorrhage or any other treatment within 3\&nbsp;months were excluded. Final analyses included 9, 6, 7, and 8 patients in groups 1 through 4, respectively. RESULTS: Patients receiving omega-3s (group 1) had\&nbsp;significantly lower levels of vitreal VEGF-A (141.11 {\textpm} 61.89 pg/mL) when compared with group 2 (626.09 {\textpm} 279.27 pg/mL; P\&nbsp;= .036) and group 3 (735.48 {\textpm} 216.43 pg/mL; P\&nbsp;= .013), but similar levels to group 4 (235.81 {\textpm} 33.99 pg/mL; P\&nbsp;= .215). All groups showed similar values for plasma VEGF-A and central foveal thickness measurements. CONCLUSIONS: This study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.07.036},
	author = {Rezende, Flavio A and Lapalme, Eric and Qian, Cynthia X and Smith, Lois E and SanGiovanni, John Paul and Sapieha, Przemyslaw}
}
@article {1635662,
	title = {Consider Myocarditis When Patients Treated with Immune Checkpoint Inhibitors Present with Ocular Symptoms},
	journal = {Oncologist},
	year = {2022},
	month = {2022 Mar 28},
	abstract = {Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG.},
	issn = {1549-490X},
	doi = {10.1093/oncolo/oyac033},
	author = {Rhee, John Y and Torun, Nurhan and Neilan, Tomas G and Guidon, Amanda C}
}
@article {1658689,
	title = {Contact Lens Safety for the Correction of Refractive Error in Healthy Eyes},
	journal = {Eye Contact Lens},
	volume = {48},
	number = {11},
	year = {2022},
	month = {2022 Nov 01},
	pages = {449-454},
	abstract = {Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.},
	keywords = {Contact Lenses, Contact Lenses, Extended-Wear, Contact Lenses, Hydrophilic, Cornea, Humans, Keratitis, Refractive Errors},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000938},
	author = {Rhee, Michelle K and Jacobs, Deborah S and Dhaliwal, Deepinder K and Szczotka-Flynn, Loretta and Prescott, Christina R and Jhanji, Vishal and Steinemann, Thomas L and Koffler, Bruce H and Jeng, Bennie H}
}
@article {1328899,
	title = {Anomalous Vertical Deviations in Attempted Abduction Occur in the Majority of Patients With Esotropic Duane Syndrome},
	journal = {Am J Ophthalmol},
	volume = {195},
	year = {2018},
	month = {2018 Nov},
	pages = {171-175},
	abstract = {PURPOSE: To describe a phenomenon, depression in attempted abduction, not previously recognized as a feature of Duane syndrome (DS). DESIGN: Retrospective, observational case series. METHODS: Setting: Institutional practice. PATIENT POPULATION: Patients diagnosed with esotropic DS at Boston Children{\textquoteright}s Hospital from 2002 to 2015. Patients with clinical photographs documenting horizontal gaze were included. Patients with prior strabismus surgery were excluded. OBSERVATION PROCEDURES: Patients were classified into 3 groups according to their vertical eye position in attempted abduction: midline group, depression group, and elevation group. Group assignment was performed by 3 independent ophthalmologists. Baseline characteristics, eye movement, and ocular deviation were compared among the 3 groups. MAIN OUTCOME MEASURES: Horizontal and vertical deviation on attempted abduction in the DS eye. RESULTS: Depression in attempted abduction was present in 74 of 113 unilateral patients (66\%) and 18 of 42 gradable eyes (43\%) of bilateral patients. Abduction limitation was significantly less severe in the midline group (median: -3.0) than in the depression group (median: -4.0) (P\&nbsp;= .01). Vertical deviation in attempted abduction was more severe in the elevation group than in the depression group (P\&nbsp;= .003). CONCLUSIONS: Depression of the eye in attempted abduction has not been widely described, yet it is present in the majority of DS patients. It is more likely to occur with more severe abduction limitation. This phenomenon is likely another form of dysinnervation in DS, the result either of anomalous vertical rectus muscle activation or asymmetric lateral rectus muscle innervation during attempted abduction. Awareness of vertical deviation in attempted abduction may facilitate surgical planning in affected patients.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.07.046},
	author = {Rhiu, Soolienah and Michalak, Suzanne and Phanphruk, Warachaya and Hunter, David G}
}
@article {1483597,
	title = {Surface modification of corneal prosthesis with nano-hydroxyapatite to enhance in vivo biointegration},
	journal = {Acta Biomater},
	volume = {107},
	year = {2020},
	month = {2020 04 15},
	pages = {299-312},
	abstract = {The majority of clinical corneal prostheses (KPros) adopt a core-skirt configuration. This configuration is favored owing to the optic core (generally a cylindrical, acrylic-based material, such as PMMA), that not only provides a clear window for the patients{\textquoteright} vision, but also confers resistance to biodegradability. The surrounding skirt (typically a biological material, such as corneal tissue) allows for host tissue integration. However, due to poor biointegration between the dissimilar core and skirt materials, it results in a weak adhesion at the interface, giving rise to clinical complications, such as bacterial infections in the tissue-PMMA interface and device extrusion. Here, we physically immobilized nano-hydroxyapatite (nHAp) on a PMMA cylinder via a dip-coating technique, to create a bioactive surface that improved biointegration in vivo. We established that the nHAp coating was safe and stable in the rabbit cornea over five weeks. More importantly, we found that apoptotic, wound healing and inflammatory responses to nHAp-coated PMMA were substantially milder than to non-coated PMMA. More mature collagen, similar to the non-operated cornea, was maintained in the corneal stroma adjacent to the nHAp-coated implant edge. However, around the non-coated cylinder, an abundant new and loose connective tissue formed, similar to bone tissue response to bioinert scaffolds. As a result of superior biointegration, tissue adhesion with nHAp-coated PMMA cylinders was also significantly enhanced compared to non-coated cylinders. This study set a precedent for the future application of the nHAp coating on clinical KPros. STATEMENT OF SIGNIFICANCE: Currently, all clinical corneal prostheses utilize as-manufactured, non-surface modified PMMA optic cylinder. The bioinert cylinder, however, has poor biointegration and adhesion with the surrounding biological tissue, which can give rise to postoperative complications, such as microbial invasion in the tissue-PMMA loose interface and PMMA optic cylinder extrusion. In the current study, we showed that surface modification of the PMMA cylinder with bioactive nano-hydroxyapatite (nHAp) significantly enhanced its biointegration with corneal stromal tissue in vivo. The superior biointegration of the nHAp-coated PMMA was signified by a more attenuated corneal wound healing, inflammatory and fibrotic response, and better tissue apposition, as well as a significantly improved corneal stromal tissue adhesion when compared to the non-coated PMMA.},
	issn = {1878-7568},
	doi = {10.1016/j.actbio.2020.01.023},
	author = {Riau, Andri K and Lwin, Nyein C and Gelfand, Larisa and Hu, Huanlong and Liedberg, Bo and Chodosh, James and Venkatraman, Subbu S and Mehta, Jodhbir S}
}
@article {1263391,
	title = {Surface Modifications of the PMMA Optic of a Keratoprosthesis to Improve Biointegration},
	journal = {Cornea},
	volume = {36 Suppl 1},
	year = {2017},
	month = {2017 Nov},
	pages = {S15-S25},
	abstract = {Biointegration of a keratoprosthesis (KPro) is critical for the mitigation of various long-term postoperative complications. Biointegration of a KPro occurs between the haptic skirt (corneal graft) and the central optic [poly(methyl methacrylate) (PMMA)]. Various studies have highlighted common problems associated with poor bonding and biointegration between these 2 incompatible biomaterials. Resolution of these issues could be achieved by surface modification of the inert material (PMMA). A calcium phosphate (CaP) coating deposited on dopamine-activated PMMA sheets by simulated body fluid incubation (d-CaP coating) was shown to improve adhesion to collagen type I (main component of corneal stroma) compared with untreated PMMA and PMMA with other surface modifications. However, the d-CaP coating could easily undergo delamination, thereby reducing its potential for modification of KPro optical cylinders. In addition, the coating did not resemble the Ca and P composition of hydroxyapatite (HAp). A novel dip-coating method that involves the creation of cavities to trap and immobilize HAp nanoparticles on the PMMA surface was introduced to address the problems associated with the d-CaP coating. The newly obtained coating offered high hydrophilicity, resistance to delamination, and preservation of the Ca and P composition of HAp. These advantages resulted in improved adhesion strength by more than 1 order of magnitude compared with untreated PMMA. With respect to biointegration, human corneal stromal fibroblasts were able to adhere strongly and proliferate on HAp-coated PMMA. Furthermore, the new coating technique could be extended to immobilization of HAp nanoparticles on 3-mm-diameter PMMA cylinders, bringing it closer to clinical application.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001352},
	author = {Riau, Andri K and Venkatraman, Subbu S and Dohlman, Claes H and Mehta, Jodhbir S}
}
@article {382226,
	title = {A teleophthalmology system for the diagnosis of ocular urgency in remote areas of Brazil},
	journal = {Arq Bras Oftalmol},
	volume = {77},
	number = {4},
	year = {2014},
	month = {2014 Aug},
	pages = {214-8},
	abstract = {PURPOSES: To validate a teleophthalmology mobile system aimed at improving and providing eye urgency screenings in remote and poor area settings in Brazil. The system enables one or more ophthalmologists to remotely examine a patient{\textquoteright}s condition and submit a decision describing the gravity of the case. If necessary, the patient can be forwarded to a hospital for further consultation. METHODS: A cellphone (Nexus One model, with a 5 megapixel camera) was used to collect data and pictures from 100 randomly selected patients at the Ophthalmology Emergency Room located at the General Hospital of the Federal University of S{\~a}o Paulo (UNIFESP). Data was then sent remotely to an online recording system to be reviewed by an ophthalmologist who provided feedback regarding the state of ocular urgency. RESULTS were then compared to the gold standard diagnosis provided at the hospital. RESULTS: The diagnosis of urgency was given by two ophthalmologists: one in the hospital (gold standard) and one remotely. When we compared both diagnoses we obtained results of 81.94\% specificity, 92.85\% sensitivity, and 85\% accuracy, with a negative predictive value of 96.72\%. This work also included a processing time analysis, resulting in an average time of 8.6 min per patient for remote consultations. CONCLUSIONS: This study is the first that has used only a cellphone for diagnosing the urgency of ocular cases. Based on our results, the system can provide a reliable distinction between urgent and non-urgent situations and can offer a viable alternative for the servicing of underprivileged areas. In screening techniques, the most important outcome is to identify urgent cases with a high level of sensitivity and predictive negative value. Thus, our results demonstrate that this tool is robust and we suggest that a major study aimed to verify its efficiency in resource-poor areas should be initiated.},
	keywords = {Brazil, Cell Phone, Computer Communication Networks, Eye Diseases, Humans, Predictive Value of Tests, Remote Consultation, Sensitivity and Specificity, Surveys and Questionnaires, Telemedicine},
	issn = {1678-2925},
	author = {Ribeiro, Anna Giselle and Rodrigues, Renan Albert Mendon{\c c}a and Guerreiro, Ana Maria and Regatieri, Caio Vinicius Saito}
}
@article {416996,
	title = {Femtosecond laser-assisted keratopigmentation for the management of visual disabilities due to peripheral iridectomies.},
	journal = {J Glaucoma},
	volume = {24},
	number = {4},
	year = {2015},
	month = {2015 Apr-May},
	pages = {e22-4},
	abstract = {PURPOSE: To report the technique and result of keratopigmentation using a femtosecond laser for the treatment of functional visual disabilities caused by peripheral iridectomies. DESIGN: Case report. METHODS: Two eyes of 2 patients underwent femtosecond laser-assisted keratopigmentation (FLAK) for moderate to severe visual dysfunction secondary to peripheral iridectomies. The main outcomes measures of the study were changes in visual-related symptoms, cosmesis, and intraoperative surgical complications. RESULTS: Following FLAK, the visual-related symptoms (ghosting, glare, and monocular diplopia) improved in both cases with significant improvement to total elimination of symptoms. No patient lost any lines of visual acuity, and no significant complications were observed during the follow-up period. The cosmetic appearance was reported as very good. CONCLUSIONS: FLAK is minimally invasive and results in a significant decrease in the subjective glare and photophobia and even in resolution of monocular diplopia. The cosmetic outcome was also favorable. This technique allows surgeons to correct visual disabilities associated with iris defects with a high success rate while avoiding more aggressive intraocular surgery.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000057},
	author = {Ricardo, Jose Reinaldo da Silva and Medhi, Jnanankar and Pineda, Roberto}
}
@article {1109866,
	title = {Guanine glycation repair by DJ-1/Park7 and its bacterial homologs},
	journal = {Science},
	volume = {357},
	number = {6347},
	year = {2017},
	month = {2017 Jul 14},
	pages = {208-211},
	abstract = {DNA damage induced by reactive carbonyls (mainly methylglyoxal and glyoxal), called DNA glycation, is quantitatively as important as oxidative damage. DNA glycation is associated with increased mutation frequency, DNA strand breaks, and cytotoxicity. However, in contrast to guanine oxidation repair, how glycated DNA is repaired remains undetermined. Here, we found that the parkinsonism-associated protein DJ-1 and its bacterial homologs Hsp31, YhbO, and YajL could repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ-1-depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient bacterial mutants displayed increased levels of glycated DNA and RNA and exhibited strong mutator phenotypes. Thus, DJ-1 and its prokaryotic homologs constitute a major nucleotide repair system that we name guanine glycation repair.},
	issn = {1095-9203},
	doi = {10.1126/science.aag1095},
	author = {Richarme, Gilbert and Liu, Cailing and Mihoub, Mouadh and Abdallah, Jad and Leger, Thibaut and Joly, Nicolas and Liebart, Jean-Claude and Jurkunas, Ula V and Nadal, Marc and Bouloc, Philippe and Dairou, Julien and Lamouri, Aazdine}
}
@article {1460379,
	title = {Successful development and clinical translation of a novel anterior lamellar artificial cornea},
	journal = {J Tissue Eng Regen Med},
	volume = {13},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {2142-2154},
	abstract = {Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue-engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin-agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical-grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.},
	issn = {1932-7005},
	doi = {10.1002/term.2951},
	author = {Rico-S{\'a}nchez, Laura and Garz{\'o}n, Ingrid and Gonz{\'a}lez-Andrades, Miguel and Ru{\'\i}z-Garc{\'\i}a, Antonio and Punzano, Miriam and Lizana-Moreno, Antonio and Mu{\~n}oz-{\'A}vila, Jose Ignacio and S{\'a}nchez-Quevedo, Maria Del Carmen and Mart{\'\i}nez-Atienza, Juliana and Lopez-Navas, Luis and Sanchez-Pernaute, Rosario and Oruezabal, Roke I{\~n}aki and Medialdea, Santiago and Gonzalez-Gallardo, Maria Del Carmen and Carmona, Gloria and Sanbonmatsu-G{\'a}mez, Sara and Perez, Mat{\'\i}as and Jimenez, Pilar and Cuende, Natividad and Campos, Antonio and Alaminos, Miguel}
}
@article {1667718,
	title = {Antimicrobial Activity of an Fmoc-Plantaricin 149 Derivative Peptide against Multidrug-Resistant Bacteria},
	journal = {Antibiotics (Basel)},
	volume = {12},
	number = {2},
	year = {2023},
	month = {2023 Feb 15},
	abstract = {Antimicrobial resistance poses a major threat to public health. Given the paucity of novel antimicrobials to treat resistant infections, the emergence of multidrug-resistant bacteria renewed interest in antimicrobial peptides as potential therapeutics. This study designed a new analog of the antimicrobial peptide Plantaricin 149 (Pln149-PEP20) based on previous Fmoc-peptides. The minimal inhibitory concentrations of Pln149-PEP20 were determined for 60 bacteria of different species and resistance profiles, ranging from 1 mg/L to 128 mg/L for Gram-positive bacteria and 16 to 512 mg/L for Gram-negative. Furthermore, Pln149-PEP20 demonstrated excellent bactericidal activity within one hour. To determine the propensity to develop resistance to Pln149-PEP20, a directed-evolution in vitro experiment was performed. Whole-genome sequencing of selected mutants with increased MICs and wild-type isolates revealed that most mutations were concentrated in genes associated with membrane metabolism, indicating the most likely target of Pln149-PEP20. Synchrotron radiation circular dichroism showed how this molecule disturbs the membranes, suggesting a carpet mode of interaction. Membrane depolarization and transmission electron microscopy assays supported these two hypotheses, although a secondary intracellular mechanism of action is possible. The molecule studied in this research has the potential to be used as a novel antimicrobial therapy, although further modifications and optimization remain possible.},
	issn = {2079-6382},
	doi = {10.3390/antibiotics12020391},
	author = {Righetto, Gabriela Marinho and Lopes, Jos{\'e} Luiz de Souza and Martins Bispo, Paulo Jos{\'e} and Andr{\'e}, Camille and Souza, Julia Medeiros and Andricopulo, Adriano Defini and Beltramini, Leila Maria and Camargo, Ilana Lopes Baratella da Cunha}
}
@article {560206,
	title = {The effect of hand movements on numerical bisection judgments in early blind and sighted individuals.},
	journal = {Cortex},
	volume = {71},
	year = {2015},
	month = {2015 Oct},
	pages = {76-84},
	abstract = {Recent evidence suggests that in representing numbers blind individuals might be affected differently by proprioceptive cues (e.g., hand positions, head turns) than are sighted individuals. In this study, we asked a group of early blind and sighted individuals to perform a numerical bisection task while executing hand movements in left or right peripersonal space and with either hand. We found that in bisecting ascending numerical intervals, the hemi-space in which the hand was moved (but not the moved hand itself) influenced the bisection bias similarly in both early blind and sighted participants. However, when numerical intervals were presented in descending order, the moved hand (and not the hemi-space in which it was moved) affected the bisection bias in all participants. Overall, our data show that the operation to be performed on the mental number line affects the activated spatial reference frame, regardless of participants{\textquoteright} previous visual experience. In particular, both sighted and early blind individuals{\textquoteright} representation of numerical magnitude is mainly rooted in world-centered coordinates when numerical information is given in canonical orientation (i.e., from small to large), whereas hand-centered coordinates become more relevant when the scanning of the mental number line proceeds in non-canonical direction.},
	issn = {1973-8102},
	doi = {10.1016/j.cortex.2015.06.005},
	author = {Rinaldi, Luca and Vecchi, Tomaso and Fantino, Micaela and Merabet, Lotfi B and Cattaneo, Zaira}
}
@article {1532361,
	title = {The Effect of Blindness on Spatial Asymmetries},
	journal = {Brain Sci},
	volume = {10},
	number = {10},
	year = {2020},
	month = {2020 Sep 23},
	abstract = {The human cerebral cortex is asymmetrically organized with hemispheric lateralization pervading nearly all neural systems of the brain. Whether the lack of normal visual development affects hemispheric specialization subserving the deployment of visuospatial attention asymmetries is controversial. In principle, indeed, the lack of early visual experience may affect the lateralization of spatial functions, and the blind may rely on a different sensory input compared to the sighted. In this review article, we thus present a current state-of-the-art synthesis of empirical evidence concerning the effects of visual deprivation on the lateralization of various spatial processes (i.e., including line bisection, mirror symmetry, and localization tasks). Overall, the evidence reviewed indicates that spatial processes are supported by a right hemispheric network in the blind, hence, analogously to the sighted. Such a right-hemisphere dominance, however, seems more accentuated in the blind as compared to the sighted as indexed by the greater leftward bias shown in different spatial tasks. This is possibly the result of the more pronounced involvement of the right parietal cortex during spatial tasks in blind individuals compared to the sighted, as well as of the additional recruitment of the right occipital cortex, which would reflect the cross-modal plastic phenomena that largely characterize the blind brain.},
	issn = {2076-3425},
	doi = {10.3390/brainsci10100662},
	author = {Rinaldi, Luca and Ciricugno, Andrea and Merabet, Lotfi B and Vecchi, Tomaso and Cattaneo, Zaira}
}
@article {1318874,
	title = {The spatial representation of number, time, and serial order following sensory deprivation: A systematic review},
	journal = {Neurosci Biobehav Rev},
	volume = {90},
	year = {2018},
	month = {2018 Jul},
	pages = {371-380},
	abstract = {The spatial representation of numerical and temporal information is thought to be rooted in our multisensory experiences. Accordingly, we may expect visual or auditory deprivation to affect the way we represent numerical magnitude and time spatially. Here, we systematically review recent findings on how blind and deaf individuals represent abstract concepts such as magnitude and time (e.g., past/future, serial order of events) in a spatial format. Interestingly, available evidence suggests that sensory deprivation does not prevent the spatial "re-mapping" of abstract information, but differences compared to normally sighted and hearing individuals may emerge depending on the specific dimension considered (i.e., numerical magnitude, time as past/future, serial order). Herein we discuss how the study of sensory deprived populations may shed light on the specific, and possibly distinct, mechanisms subserving the spatial representation of these concepts. Furthermore, we pinpoint unresolved issues that need to be addressed by future studies to grasp a full understanding of the spatial representation of abstract information associated with visual and auditory deprivation.},
	issn = {1873-7528},
	doi = {10.1016/j.neubiorev.2018.04.021},
	author = {Rinaldi, Luca and Merabet, Lotfi B and Vecchi, Tomaso and Cattaneo, Zaira}
}
@article {1814326,
	title = {Music During Cataract Surgery: Impact on Anxiety},
	journal = {J Cataract Refract Surg},
	year = {2024},
	month = {2024 Mar 19},
	abstract = {PURPOSE: To determine the effect of playing patient-selected music intra-operatively on patient self-reported anxiety and the amount of sedative administered during cataract surgery. SETTING: Yale New Haven Hospital health system, New Haven, CT. DESIGN: Prospective, randomized, controlled clinical trial. METHODS: Patients were randomized to either music group or control group, which had no music played. Patients were blinded to the purpose of the study. On postoperative day 1, patients were consented to participate in the study and asked to complete a six-question Likert-style survey (modified from the State-Trait Anxiety Inventory) assessing anxiety at baseline and during surgery. Patients{\textquoteright} intraoperative and postoperative vitals were recorded. The medication, dosage, and number of sedative injections given were also recorded. Paired t-tests were used to assess for significant differences between the two groups. RESULTS: A total of 107 patients (mean age 71.2 years) were enrolled in the study. There was no significant difference in baseline anxiety between the two groups. Patients randomized to the music group had significantly lower total self-reported anxiety (mean 5.98) than the control group (mean 7.13, p=0.006). Moreover, patients exposed to music felt significantly less frightened, nervous, and confused during surgery (p=0.002, 0.007, and 0.017, respectively). There was no significant difference between the groups in number and dosage of sedatives given. CONCLUSION: Playing patient-selected music during cataract surgery is an effective way to decrease anxiety. Music has a direct impact on patient experience and is an inexpensive, low-risk method of reducing patient anxiety during surgery.},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000001444},
	author = {Rivera, Paola A and Linderman, Wendy L and Miguez, Sofia and Chow, Jessica and DeBroff, Brian and Diaz, Vicente}
}
@article {1363191,
	title = {Festschrift for Simmons Lessell, MD},
	journal = {J Neuroophthalmol},
	volume = {33},
	number = {4},
	year = {2013},
	month = {2013 Dec},
	pages = {e26-7},
	keywords = {Aged, Awards and Prizes, History, 20th Century, History, 21st Century, Humans, Male, Neurology, New York, Ophthalmology},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000056},
	author = {Rizzo, Joseph F}
}
@article {1748536,
	title = {Orbital Vasculopathy With Unexpected Finding of Calcium Oxalosis in the Context of a Clinical Diagnosis of Optic Neuropathy},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 Aug 29},
	abstract = {BACKGROUND: There are few reports of histopathology of any form of optic neuropathy. This article provides histopathologic findings of an adult-onset, nonprogressive optic neuropathy that was diagnosed clinically as nonacute, nonarteritic anterior ischemic optic neuropathy (NAION) but which was found by a pathological study to be associated with diffuse calcium oxalosis that was confined in the involved orbit. METHODS: This is a case report that includes results of a neuro-ophthalmologic examination and histopathology of a complete autopsy, including en bloc removal of both orbits and the brain. The unaffected orbit/optic nerve served as a control. The affected orbit was serially sectioned into 2,550 increments each separated by 10 μm; the uninvolved orbit was sectioned into 150 equally spaced sections. The main outcome measures were derived from the autopsy, especially from the thin-section histopathologic study of both orbits that focused on blood vessels and the site of neural damage within the optic nerve. RESULTS: The neuro-ophthalmologic examination revealed a unilateral optic neuropathy with pallor of the left optic nerve head that had been documented just before death. The general autopsy showed acute bacterial endocarditis and a recent cerebral hematoma that caused death. Histopathology revealed sectoral loss of optic nerve axons in the left eye. Numerous arterial walls in the left orbit, including short posterior ciliary arteries and the central retinal artery, contained hundreds of crystals with anisotropic, colorful birefringence consistent with calcium oxalosis. Crystals were not found in the right, control orbit or elsewhere in the body. CONCLUSIONS: The patient developed an optic neuropathy late in life that was diagnosed by an experienced neuro-ophthalmologist as being most consistent with nonacute, nonarteritic anterior ischemic optic neuropathy. The autopsy identified sectoral loss of optic nerve fibers consistent with that diagnosis. However, the unexpected discovery of calcium oxalate crystals in blood vessels of the involved orbit, which curiously were not present elsewhere in the body, raises a question of their etiological role in this particular optic neuropathy. Whether the crystals were causal, epiphenomenal, or purely incidental to the optic neuropathy cannot be answered by our study.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001906},
	author = {Rizzo, Joseph F and Sanders, Delia T and Castelbuono, Anthony C}
}
@article {1478343,
	title = {Unraveling the Enigma of Nonarteritic Anterior Ischemic Optic Neuropathy},
	journal = {J Neuroophthalmol},
	volume = {39},
	number = {4},
	year = {2019},
	month = {2019 Dec},
	pages = {529-544},
	abstract = {Non-arteritic anterior ischemic optic neuropathy (NAON) is the second most common optic neuropathy in adults. Despite extensive study, the etiology of NAION is not definitively known. The best evidence suggests that NAION is caused by an infarction in the region of the optic nerve head (ONH), which is perfused by paraoptic short posterior ciliary arteries (sPCAs) and their branches. To examine the gaps in knowledge that defies our understanding of NAION, a historical review was performed both of anatomical investigations of the ONH and its relevant blood vessels and the evolution of clinical understanding of NAION. Notably, almost all of the in vitro vascular research was performed prior our current understanding of NAION, which has largely precluded a hypothesis-based laboratory approach to study the etiological conundrum of NAION. More recent investigative techniques, like fluorescein angiography, have provided valuable insight into vascular physiology, but such light-based techniques have not been able to image blood vessels located within or behind the dense connective tissue of the sclera and laminar cribrosa, sites that are likely culpable in NAION. The lingering gaps in knowledge clarify investigative paths that might be taken to uncover the pathogenesis of NAION and possibly glaucoma, the most common optic neuropathy for which evidence of a vascular pathology also exists.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000870},
	author = {Rizzo, Joseph F}
}
@article {1782411,
	title = {The Role of Epigenetics in Accelerated Aging: A Reconsideration of Later-Life Visual Loss After Early Optic Neuropathy},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 Nov 06},
	abstract = {BACKGROUND: In 2005, we reported 3 patients with bilateral optic nerve damage early in life. These patients had stable vision for decades but then experienced significant bilateral vision loss with no obvious cause. Our hypothesis, novel at that time, was that the late decline of vision was due to age-related attrition of retinal ganglion cells superimposed on a reduced neuronal population due to the earlier injury. EVIDENCE ACQUISITION: The field of epigenetics provides a new paradigm with which to consider the normal aging process and the impact of neuronal injury, which has been shown to accelerate aging. Late-in-life decline in function after early neuronal injury occurs in multiple sclerosis due to dysregulated inflammation and postpolio syndrome. Recent studies by our group in mice have also demonstrated the possibility of partial reversal of cellular aging and the potential to mitigate anatomical damage after injury and even improve visual function. RESULTS: The results in mice and nonhuman primates published elsewhere have shown enhanced neuronal survival and visual function after partial epigenetic reprogramming. CONCLUSIONS: Injury promotes epigenetic aging, and this finding can be observed in several clinically relevant scenarios. An understanding of the epigenetic mechanisms at play opens the opportunity to restore function in the nervous system and elsewhere with cellular rejuvenation therapies. Our earlier cases exemplify how reconsideration of previously established concepts can motivate inquiry of new paradigms.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000002041},
	author = {Rizzo, Joseph F and Shah, Madhura P and Krasniqi, Drenushe and Lu, Yuancheng Ryan and Sinclair, David A and Ksander, Bruce R}
}
@article {1364532,
	title = {Developmental conjunctival cyst of the eyelid in a child},
	journal = {J AAPOS},
	volume = {16},
	number = {2},
	year = {2012},
	month = {2012 Apr},
	pages = {196-8},
	abstract = {Conjunctival cysts unrelated to surgery or trauma are uncommon adnexal lesions in children and may be difficult to recognize. We report the clinical and pathological findings of an apparently spontaneous conjunctival cyst in the upper eyelid of a child whose first ophthalmological examination was at 7 months of age. The cyst was surgically excised at 5 years of age.},
	keywords = {Biomarkers, Child, Preschool, Conjunctival Diseases, Cysts, Eyelid Diseases, Humans, Magnetic Resonance Imaging, Male, Ophthalmologic Surgical Procedures},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2012.02.001},
	author = {Robb, Richard M and Elliott, Alexandra T and Robson, Caroline D}
}
@article {439706,
	title = {Anterior chamber gas bubble emergence pattern during femtosecond LASIK-flap creation.},
	journal = {Br J Ophthalmol},
	volume = {99},
	number = {9},
	year = {2015},
	month = {2015 Sep},
	pages = {1201-5},
	abstract = {AIM: To characterise the emergence pattern of cavitation bubbles into the anterior chamber (AC) following femtosecond laser-assisted in situ keratomileusis (LASIK)-flap creation METHODS: Retrospective review of patients undergoing femtosecond LASIK surgery at Boston Laser, a private refractive surgery practice in Boston, Massachusetts, between December 2008 and February 2014. Patient charts were reviewed to identify all cases with gas bubble migration into the AC. Surgical videos were examined and the location of bubble entry was recorded separately for right and left eyes. RESULTS: Five thousand one hundred and fifty-eight patients underwent femtosecond LASIK surgery. Air bubble migration into the AC, presumably via the Schlemm{\textquoteright}s canal and trabecular meshwork, occurred in 1\% of cases. Patients with AC bubbles had an average age of 33{\textpm}8 years with a measured LASIK flap thickness of 96{\textpm}21 μm. The occurrence of gas bubbles impaired iris registration in 64\% of cases. Gas bubbles appeared preferentially in the nasal or inferior quadrants for right (92\% of cases) and left (100\% of cases) eyes. This bubble emergence pattern is significantly different from that expected with a random distribution (p\&lt;0.0001) and did not seem associated with decentration of the femtosecond laser docking system. CONCLUSIONS: The migration of gas bubbles into the AC is a rare occurrence during femtosecond laser flap creation. The preferential emergence of gas bubbles into the nasal and inferior quadrants of the AC may indicate a distinctive anatomy of the nasal Schlemm{\textquoteright}s canal.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-306307},
	author = {Robert, Marie-Claude and Khreim, Nour and Todani, Amit and Melki, Samir A}
}
@article {341756,
	title = {Collagen cross-linking of the Boston keratoprosthesis donor carrier to prevent corneal melting in high-risk patients.},
	journal = {Eye Contact Lens},
	volume = {40},
	number = {6},
	year = {2014},
	month = {2014 Nov},
	pages = {376-81},
	abstract = {OBJECTIVE: To examine the clinical relevance and pathophysiology of Boston keratoprosthesis (B-KPro)-related corneal keratolysis (cornea melt) and to describe a novel method of preventing corneal melt using ex vivo crosslinked cornea tissue carrier. METHODS: A review of B-KPro literature was performed to highlight cases of corneal melt. Studies examining the effect of corneal collagen cross-linking (CXL) on the biomechanical properties of corneal tissue are summarized. The use of crosslinked corneal tissue as a carrier to the B-KPro is illustrated with a case. RESULTS: Corneal melting after B-KPro is a relatively rare event, occurring in 3\% of eyes during the first 3 years of postoperative follow-up. The risk of post-KPro corneal melting is heightened in eyes with chronic ocular surface inflammation such as eyes with Stevens-Johnson syndrome and mucous membrane pemphigoid. This chronic inflammation results in high tear levels of matrix metalloproteinases, the enzymes responsible for collagenolysis and corneal melt. Crosslinked corneal tissue has been shown to have stiffer biomechanical properties and to be more resistant to degradation by collagenolytic enzymes. We have previously optimized the technique for ex vivo corneal CXL and are currently studying its impact on the prevention of corneal melting after B-KPro surgery in high-risk eyes. Crosslinked carrier tissue was used in a 52-year-old man with familial aniridia and severe post-KPro corneal melt. The patient maintained his visual acuity and showed no evidence of corneal thinning or melt in the first postoperative year. CONCLUSION: Collagen crosslinking was previously shown to halt the enzymatic degradation of corneal buttons ex vivo. This study demonstrates the safety and potential benefit of using crosslinked corneal grafts as carriers for the B-KPro, especially in eyes at higher risk of postoperative melt.},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000081},
	author = {Robert, Marie-Claude and Arafat, Samer N and Ciolino, Joseph B}
}
@article {836946,
	title = {Tear Matrix Metalloproteinases and Myeloperoxidase Levels in Patients With Boston Keratoprosthesis Type I.},
	journal = {Cornea},
	volume = {35},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {1008-14},
	abstract = {PURPOSE: To investigate the tear levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 in eyes after Boston keratoprosthesis type I (B-KPro) implantation and to correlate these markers with the established B-KPro prognostic categories. METHODS: Tear washes were collected from 40 patients (7 with autoimmune disease, 2 with chemical burn, and 31 with other noncicatrizing diagnoses). Tear levels of MMPs, MPO, and tissue inhibitor of metalloproteinase-1 were quantified using multianalyte bead-based enzyme-linked immunosorbent assays. The total MMP activity was determined using a fluorimetric assay. The analytes were compared to the underlying diagnosis and other clinical factors. RESULTS: The MMP-8, MMP-9, and MPO levels were markedly elevated in the eyes with B-KPro (80 {\textpm} 31, 291 {\textpm} 77, and 244 {\textpm} 33 pg/μg, respectively). Chemical burn was associated with significantly higher tear MMP-8 (474 {\textpm} 376 pg/μg) and MMP-9 levels (1300 {\textpm} 635 pg/μg) compared with noncicatrizing diseases (MMP-8: 41 {\textpm} 15 pg/μg, P = 0.02 and MMP-9: 196 {\textpm} 57 pg/μg, P = 0.02) and higher MMP-9 levels compared with autoimmune diseases (MMP-8: 96 {\textpm} 65 pg/μg, P = 0.21 and MMP-9: 306 {\textpm} 196 pg/μg, P = 0.04). Similar analyte levels were observed in the B-KPro eye and the contralateral non-B-KPro eye of patients with bilateral diseases. MMP-8, MMP-9, and total MMP activities correlated strongly with each other. CONCLUSIONS: In the eyes with B-KPro, tear MMP-8 and MMP-9 levels seem to be related to the underlying ocular surface pathology and not significantly influenced by the presence of the prosthesis.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000893},
	author = {Robert, Marie-Claude and Arafat, Samer N and Spurr-Michaud, Sandra and Chodosh, James and Dohlman, Claes H and Gipson, Ilene K}
}
@article {669326,
	title = {A Drug Delivery System for Administration of Anti-TNF-α Antibody.},
	journal = {Transl Vis Sci Technol},
	volume = {5},
	number = {2},
	year = {2016},
	month = {2016 Mar},
	pages = {11},
	abstract = {PURPOSE: To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti-TNF-α antibody administration. METHODS: A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100-300 μm in diameter porosity) loaded with 10\% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti-TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37{\textdegree}C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months. RESULTS: Gamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37{\textdegree}C for 1 month had no deleterious effects on antibody affinity. Anti-TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants. CONCLUSIONS: Sustained local delivery of anti-TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye. TRANSLATIONAL RELEVANCE: The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy.},
	issn = {2164-2591},
	doi = {10.1167/tvst.5.2.11},
	author = {Robert, Marie-Claude and Frenette, Mathieu and Zhou, Chengxin and Yan, Yueran and Chodosh, James and Jakobiec, Frederick A and Stagner, Anna M and Vavvas, Demetrios and Dohlman, Claes H and Paschalis, Eleftherios I}
}
@article {680426,
	title = {Infliximab after Boston Keratoprosthesis in Stevens-Johnson Syndrome: An Update.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Mar 25},
	pages = {1-5},
	abstract = {PURPOSE: To report our experience using intravenous infliximab for the treatment of tissue melt after Boston keratoprosthesis (B-KPro) types I and II in patients with autoimmune disease. METHODS: Case series. RESULTS: We identified four patients who were treated with intravenous infliximab in the context of tissue melt after B-KPro. Stevens-Johnson syndrome-associated corneal blindness was the primary surgical indication for B-KPro implantation in all patients. Two patients received a B-KPro type I and two patients received a B-KPro type II. The patients received intravenous infliximab for skin retraction around B-KPro type II, melting of the carrier graft or leak. Treatment resulted in a dramatic decrease in inflammation and, in some cases, arrest of the melting process. Cost and patient adherence were limiting factors to pursuing infliximab therapy. In addition, one patient developed infusion reactions. CONCLUSIONS: Intravenous infliximab may be considered as globe- and sight-saving therapy for tissue melt after B-KPro.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2016.1145237},
	author = {Robert, Marie-Claude and {\v C}rnej, Alja and Shen, Lucy Q and Papaliodis, George N and Dana, Reza and Foster, C Stephen and Chodosh, James and Dohlman, Claes H}
}
@article {1213846,
	title = {Patient Harm in Cataract Surgery: A Series of Adverse Events in Massachusetts},
	journal = {Anesth Analg},
	volume = {126},
	number = {5},
	year = {2018},
	month = {2018 May},
	pages = {1548-1550},
	abstract = {Massachusetts state agencies received reports of 37 adverse events (AEs) involving cataract surgery from 2011 to 2015. Fifteen were anesthesia related, including 5 wrong eye blocks, 3 cases of hemodynamic instability, 2 retrobulbar hematoma/hemorrhages, and 5 globe perforations resulting in permanent loss of vision. While Massachusetts{\textquoteright} reported AEs likely underrepresent the true number of AEs that occur during cataract surgery, they do offer useful signal data to indicate the types of patient harm occurring during these procedures.},
	issn = {1526-7598},
	doi = {10.1213/ANE.0000000000002526},
	author = {Roberto, Sarah A and Bayes, Joseph and Karner, Paul E and Morley, Michael G and Nanji, Karen C}
}
@article {1782351,
	title = {Somatic TET2 Mutations are Associated with Giant Cell Arteritis},
	journal = {Arthritis Rheumatol},
	year = {2023},
	month = {2023 Nov 01},
	abstract = {OBJECTIVE: Giant cell arteritis (GCA) is an age-related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HM). How the presence of somatic mutations which drive development of HM, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood. METHODS: To examine an association between CH and GCA, we analyzed sequenced exomes of 470960 UK Biobank participants for the presence of CH and used multivariable Cox regression. To examine the clinical phenotype of GCA in patients with and without somatic mutations across the spectrum of CH to HM, we performed targeted sequencing of blood samples and electronic health record review on 114 patients with GCA seen at our institution. We then examined associations between specific clonal mutations and GCA disease manifestations. RESULTS: UKB participants with CH had a 1.48-fold increased risk of incident GCA compared to UKB participants without CH. GCA risk was highest among individuals with cytopenia (HR 2.98, p\&nbsp;=\&nbsp;0.00178) and with TET2 mutation (HR 2.02, p\&nbsp;=\&nbsp;0.00116). Mutations were detected in 27.2\% of our institutional GCA cohort, 3 of whom had HM at GCA diagnosis. TET2 mutations were associated with vision loss in patients with GCA (OR 4.33, p\&nbsp;=\&nbsp;0.047). CONCLUSIONS: CH increases risk for development of GCA in a genotype-specific fashion, with greatest risk being conferred by the presence of mutations in TET2. Somatic TET2 mutations likewise increase the risk of GCA-associated vision loss. Integration of somatic genetic testing in GCA diagnostics may be warranted in the future. This article is protected by copyright. All rights reserved.},
	issn = {2326-5205},
	doi = {10.1002/art.42738},
	author = {Robinette, Michelle L and Weeks, Lachelle D and Kramer, Ryan J and Agrawal, Mridul and Gibson, Christopher J and Yu, Zhi and Sekar, Aswin and Mehta, Arnav and Niroula, Abhishek and Brown, Jared T and McDermott, Gregory C and Reshef, Edith R and Lu, Jonathan E and Liou, Victor D and Chiou, Carolina A and Natarajan, Pradeep and Freitag, Suzanne K and Rao, Deepak A and Ebert, Benjamin L}
}
@article {1363193,
	title = {Molecular evolution of human adenoviruses},
	journal = {Sci Rep},
	volume = {3},
	year = {2013},
	month = {2013},
	pages = {1812},
	abstract = {The recent emergence of highly virulent human adenoviruses (HAdVs) with new tissue tropisms underscores the need to determine their ontogeny. Here we report complete high quality genome sequences and analyses for all the previously unsequenced HAdV serotypes (n = 20) within HAdV species D. Analysis of nucleotide sequence variability for these in conjunction with another 40 HAdV prototypes, comprising all seven HAdV species, confirmed the uniquely hypervariable regions within species. The mutation rate among HAdV-Ds was low when compared to other HAdV species. Homologous recombination was identified in at least two of five examined hypervariable regions for every virus, suggesting the evolution of HAdV-Ds has been highly dependent on homologous recombination. Patterns of alternating GC and AT rich motifs correlated well with hypervariable region recombination sites across the HAdV-D genomes, suggesting foci of DNA instability lead to formulaic patterns of homologous recombination and confer agility to adenovirus evolution.},
	keywords = {Adenovirus Infections, Human, Adenoviruses, Human, DNA, Viral, Evolution, Molecular, Genome, Viral, Humans, Phylogeny, Recombination, Genetic, Sequence Analysis, DNA},
	issn = {2045-2322},
	doi = {10.1038/srep01812},
	author = {Robinson, Christopher M and Singh, Gurdeep and Lee, Jeong Yoon and Dehghan, Shoaleh and Rajaiya, Jaya and Liu, Elizabeth B and Yousuf, Mohammad A and Betensky, Rebecca A and Jones, Morris S and Dyer, David W and Seto, Donald and Chodosh, James}
}
@article {1363192,
	title = {Predicting the next eye pathogen: analysis of a novel adenovirus},
	journal = {MBio},
	volume = {4},
	number = {2},
	year = {2013},
	month = {2013 Apr 09},
	pages = {e00595-12},
	abstract = {UNLABELLED: For DNA viruses, genetic recombination, addition, and deletion represent important evolutionary mechanisms. Since these genetic alterations can lead to new, possibly severe pathogens, we applied a systems biology approach to study the pathogenicity of a novel human adenovirus with a naturally occurring deletion of the canonical penton base Arg-Gly-Asp (RGD) loop, thought to be critical to cellular entry by adenoviruses. Bioinformatic analysis revealed a new highly recombinant species D human adenovirus (HAdV-D60). A synthesis of in silico and laboratory approaches revealed a potential ocular tropism for the new virus. In vivo, inflammation induced by the virus was dramatically greater than that by adenovirus type 37, a major eye pathogen, possibly due to a novel alternate ligand, Tyr-Gly-Asp (YGD), on the penton base protein. The combination of bioinformatics and laboratory simulation may have important applications in the prediction of tissue tropism for newly discovered and emerging viruses. IMPORTANCE: The ongoing dance between a virus and its host distinctly shapes how the virus evolves. While human adenoviruses typically cause mild infections, recent reports have described newly characterized adenoviruses that cause severe, sometimes fatal human infections. Here, we report a systems biology approach to show how evolution has affected the disease potential of a recently identified novel human adenovirus. A comprehensive understanding of viral evolution and pathogenicity is essential to our capacity to foretell the potential impact on human disease for new and emerging viruses.},
	keywords = {Adenoviridae Infections, Adenoviruses, Human, Amino Acid Sequence, Animals, Cell Line, Disease Models, Animal, DNA, Viral, Eye Diseases, Female, Humans, Infant, Newborn, Male, Mice, Mice, Inbred C57BL, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Alignment, Sequence Analysis, DNA, Sequence Deletion, Systems Biology, Viral Proteins, Viral Tropism},
	issn = {2150-7511},
	doi = {10.1128/mBio.00595-12},
	author = {Robinson, Christopher M and Zhou, Xiaohong and Rajaiya, Jaya and Yousuf, Mohammad A and Singh, Gurdeep and DeSerres, Joshua J and Walsh, Michael P and Wong, Sallene and Seto, Donald and Dyer, David W and Chodosh, James and Jones, Morris S}
}
@article {742311,
	title = {Diurnal Tracking of Blink and Relationship to Signs and Symptoms of Dry Eye.},
	journal = {Cornea},
	volume = {35},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {1104-11},
	abstract = {PURPOSE: To assess diurnal changes in the signs and symptoms of dry eyes and their relationship to diurnal interblink interval (IBI) in normal subjects and in subjects with dry eye. METHODS: Blink data were collected from 9:00 AM to 8:00 PM during 2 days of normal activity using an electrocardiogram monitoring device. All subjects recorded ocular discomfort (0-5 scale) and primary activity hourly each day in a diary. Inferior and central fluorescein staining was graded by slit lamp (0-4) at the start and end of each day. Blink activity was detected using an algorithm based on recognition of the waveform corresponding to the kinematic properties of the blink signal. RESULTS: Normal subjects (N = 12) reported negligible symptoms, and results did not show a diurnal change in group hourly IBI. Mean daily IBI for the group with dry eye (N = 15) (4.63 {\textpm} 1.63 s) was shorter than that for the normal group (5.28 {\textpm} 1.48 s) (P = 0.0483). Correlation of diurnal symptoms and mean hourly IBI was relatively weak (r = -0.248). A repeated-measures model found IBI to be significantly associated with the time of day (P = 0.0028). Inferior corneal staining showed a small but significant diurnal increase for both normal group and group with dry eyes. CONCLUSIONS: Diurnal blink tracking reveals significant trending with symptoms. Diurnal change in IBI may be an appropriate surrogate for symptoms in the study of dry eye.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000885},
	author = {Rodriguez, John D and Lane, Keith J and Ousler, George W and Angjeli, Endri and Smith, Lisa M and Bateman, Kirk M and Abelson, Mark B}
}
@article {1474196,
	title = {An Alternative Psychophysical Diagnostic Indicator of the Aging Eye},
	journal = {J Ophthalmol},
	volume = {2019},
	year = {2019},
	month = {2019},
	pages = {2036192},
	abstract = {Purpose: Impaired adaptation to changes in lighting levels as well as mesopic visual function is a common complaint in those over the age of 65. The use of photostress is a well-established method to test the adaption rate and the response of the visual cycle. In this study, we test visual function recovery to mesopic luminance stimuli following a long duration photostress in young and elderly subjects. If successful in strongly differentiating aging macular function, these methods may also be useful in the study of pathologies such as age-related macular degeneration. Methods: A group of 12 older normal subjects (mean age 75.1 {\textpm} 4.79) and a control group of 5 younger normal subjects (mean age 26.2 {\textpm} 4.19) were subjected to macular photostress using the OraLux photostress system. The OraLux system provides a diffuse light source bleaching 84\% of cone photopigment while maintaining an exposure safety factor of 200 times less than the maximum safe exposure. After each photostressing session, macular recovery was tracked using a foveal, variable contrast, flickering stimulus of mean luminance in the high mesopic range. Recovery was tracked for 300 seconds. The endpoint was time to recovery to each individual{\textquoteright}s baseline sensitivity as determined by two static sensitivity trials prior to photostress. Results: Proportional hazards analysis of recovery time yielded a statistically significant difference between the older group and the young group (HR = 0.181; =0.0289). The estimated hazard ratio of 0.181 indicates that older subjects return to baseline at less than one-fifth the rate of younger subjects. The hazards ratio remained statistically significant after adjusting for visual acuity (HR = 0.093; =0.0424). Conclusion: Photostress recovery of flicker sensitivity under mesopic conditions is a strong differentiator of aging macular function. This agrees with subject-reported complaints in reduced luminance conditions after exposure to bright lights such as night driving. The qualitative similarity between the aging retina and changes in early AMD suggests that flicker recovery following photostress may be useful as a surrogate endpoint in AMD clinical trials.},
	issn = {2090-004X},
	doi = {10.1155/2019/2036192},
	author = {Rodriguez, John D and Wallstrom, Garrick and Narayanan, Divya and Welch, Donna and Abelson, Mark B}
}
@article {1233406,
	title = {Blink: Characteristics, Controls, and Relation to Dry Eyes},
	journal = {Curr Eye Res},
	volume = {43},
	number = {1},
	year = {2018},
	month = {2018 Jan},
	pages = {52-66},
	abstract = {Blink is a complex phenomenon that is profoundly affected by diverse endogenous and exogenous stimuli. It has been studied in the context of cognition, emotional, and psychological states, as an indicator of fatigue and sleepiness, particularly in the automobile and transportation industry, in visual tasking, and finally, as it relates to tear film stability and ocular surface health. The fact that it is highly variable and has input from so many sources makes it very difficult to study. In the present review, the behavior of blink in many of these systems is discussed, ultimately returning in each instance to a discussion of how these factors affect blink in the context of dry eyes. Blink is important to ocular surface health and to an individual{\textquoteright}s optimal functioning and quality of life. Disturbances in blink, as cause or effect, result in a breakdown of tear film stability, optical clarity, and visual function.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2017.1381270},
	author = {Rodriguez, John D and Lane, Keith J and Ousler, George W and Angjeli, Endri and Smith, Lisa M and Abelson, Mark B}
}
@article {1304391,
	title = {Glycosylation pathways at the ocular surface},
	journal = {Biochem Soc Trans},
	volume = {46},
	number = {2},
	year = {2018},
	month = {2018 Apr 17},
	pages = {343-350},
	abstract = {Glycosylation is a major form of enzymatic modification of organic molecules responsible for multiple biological processes in an organism. The biosynthesis of glycans is controlled by a series of glycosyltransferases, glycosidases and glycan-modifying enzymes that collectively assemble and process monosaccharide moieties into a diverse array of structures. Many studies have provided insight into various pathways of glycosylation at the ocular surface, such as those related to the biosynthesis of mucin-type -glycans and -glycans on proteins, but many others still remain largely unknown. This review provides an overview of the different classes of glycans described at the ocular surface focusing on their biosynthetic pathways and biological relevance. A precise understanding of these pathways under physiological and pathological conditions could help identify biomarkers and novel targets for therapeutic intervention.},
	issn = {1470-8752},
	doi = {10.1042/BST20170408},
	author = {Rodriguez Benavente, Maria C and Arg{\"u}eso, Pablo}
}
@article {382431,
	title = {Retinoblastoma.},
	journal = {Pediatr Clin North Am},
	volume = {62},
	number = {1},
	year = {2015},
	month = {2015 Feb},
	pages = {201-23},
	abstract = {Retinoblastoma is the most common neoplasm of the eye in childhood, and represents 3\% of all childhood malignancies. Retinoblastoma is a cancer of the very young; two-thirds are diagnosed before 2\&nbsp;years of age and 95\% before 5\&nbsp;years. Retinoblastoma presents in 2 distinct clinical forms: (1) a bilateral or multifocal, heritable form (25\% of all cases), characterized by the presence of germline mutations of the RB1 gene; and (2) a unilateral or unifocal form (75\% of all cases), 90\% of which are nonhereditary. The treatment of retinoblastoma is multidisciplinary and is designed primarily to save life and preserve vision.},
	keywords = {Genes, Retinoblastoma, Humans, Mutation, Neoplasm Staging, Retinal Neoplasms, Retinoblastoma},
	issn = {1557-8240},
	doi = {10.1016/j.pcl.2014.09.014},
	author = {Rodriguez-Galindo, Carlos and Orbach, Darren B and Vanderveen, Deborah}
}
@article {1580479,
	title = {GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Feb 26},
	pages = {4738},
	abstract = {To analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Na{\"\i}ve and non-na{\"\i}ve DME patients were treated with DEX, with visual acuity (VA) >= 0.2 logMAR and central subfield thickness (CST) of >= 300\&nbsp;{\textmu}m. Functional and anatomical responses were graded after 2 and 4\&nbsp;months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment na{\"\i}ve eyes). Compared to non-na{\"\i}ve eyes, na{\"\i}ve eyes showed a very good functional response (VA gain >= 10 letters) more frequently after 2 and 4\&nbsp;months (56\% and 57\% [na{\"\i}ve] vs. 33\% and 28\% [non-na{\"\i}ve], p \&lt; 0.001). A VA gain \&lt; 5 letters (non-response) after 2 and 4\&nbsp;months was seen in 18\% and 16\% of na{\"\i}ve eyes, and in 49\% and 53\% of non-na{\"\i}ve eyes (p \&lt; 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-na{\"\i}ve eyes (12\% vs. 4\%, p = 0.003). Functionally and anatomically, na{\"\i}ve eyes showed most frequently an early and stable improvement (functionally: 77/175 44\%; anatomically: 123/175 eyes, 70\%). Most non-na{\"\i}ve eyes experienced no significant improvement functionally (97/242 eyes, 40\%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42\%). Functional but not anatomical response patterns were influenced by baseline VA. Na{\"\i}ve and non-na{\"\i}ve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in na{\"\i}ve eyes, whereas anatomical non-response is unusual in both groups.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-79288-w},
	author = {Rodr{\'\i}guez-Vald{\'e}s, Patricio J and Rehak, Matus and Zur, Dinah and Sala-Puigdollers, Anna and Fraser-Bell, Samantha and Lupidi, Marco and Chhablani, Jay and Cebeci, Zafer and La{\'\i}ns, In{\^e}s and Chaikitmongkol, Voraporn and Fung, Adrian T and Okada, Mali and Unterlauft, Jan Darius and Smadar, Lital and Loewenstein, Anat and Iglicki, Matias and Busch, Catharina}
}
@article {1347443,
	title = {Central Retinal Vein Occlusion with Chorioretinal Folds Secondary to Active Thyroid Eye Disease},
	journal = {Ophthalmology},
	volume = {125},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {1645},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.07.001},
	author = {Roelofs, Kelsey A and Eliott, Dean and Freitag, Suzanne K}
}
@article {1328900,
	title = {Orbital Emphysema: A Case Report and Comprehensive Review of the Literature},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {1},
	year = {2019},
	month = {2019 Jan/Feb},
	pages = {1-6},
	abstract = {PURPOSE: The objective of this study was to report a case of persistent and likely self-induced orbital emphysema (OE) following functional endoscopic sinus surgery with dislodgement of a previously placed orbital floor implant and to review the literature surrounding etiologies, pathophysiology, and management of OE. METHODS: Case report and review of the literature. RESULTS AND DISCUSSION: While blunt trauma resulting in disruption of the medial orbital wall is the most common cause of OE, there are an additional 25 underlying etiologies reported in the current literature. Pathophysiology of OE is somewhat dependent on underlying etiology but often involves a 1-way ball valve mechanism such that air may enter the orbit but not exit. When sufficient air enters the orbit, complications secondary to increased intraorbital pressure, including central retinal artery occlusion and compressive optic neuropathy, can occur. Mild cases of OE are typically observed, with most resolving within 7 to 10 days. Moderate cases are often managed by lateral canthotomy and cantholysis with possible needle decompression. Severe cases may require urgent surgical decompression. While the majority of cases of OE are benign and self-limited, there have been 4 reports in the literature documenting significant vision loss. CONCLUSIONS: Although there is often a history of trauma in patients presenting with OE, many other underlying etiologies have been reported with several cases occurring spontaneously. As such, OE should be included on the differential for a patient presenting with a sudden onset of orbital signs.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001216},
	author = {Roelofs, Kelsey A and Starks, Victoria and Yoon, Michael K}
}
@article {560186,
	title = {The role of serological titres in the diagnosis of ocular toxoplasmosis.},
	journal = {Acta Ophthalmol},
	volume = {94},
	number = {5},
	year = {2016},
	month = {2016 Aug},
	pages = {521-2},
	issn = {1755-3768},
	doi = {10.1111/aos.12851},
	author = {Roh, Miin and Yasa, Cagla and Cho, Heeyoon and Nicholson, Laura and Uchiyama, Eduardo and Young, Lucy H Y and Lobo, Ann-Marie and Papaliodis, George N and Durand, Marlene L and Sobrin, Lucia}
}
@article {1424815,
	title = {Microperimetry in age-related macular degeneration: association with macular morphology assessed by optical coherence tomography},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {1769-1776},
	abstract = {BACKGROUND/AIMS: Microperimetry is a technique that is increasingly used to assess visual function in age-related macular degeneration (AMD). In this study, we aimed to evaluate the relationship between retinal sensitivity measured with macular integrity assessment (MAIA) microperimetry and optical coherence tomography (OCT)-based macular morphology in AMD. METHODS: Prospective, cross-sectional study. All participants were imaged with colour fundus photographs used for AMD staging (Age-Related Eye Disease Study scale), spectral-domain OCT (Spectralis, Heidelberg, Germany) and swept-source OCT (Topcon, Japan). Threshold retinal sensitivity of the central 10{\textdegree} diameter circle was assessed with the full-threshold, 37-point protocol of the MAIA microperimetry device (Centervue, Italy). Univariable and multivariable multilevel mixed-effect linear regression models were used for analysis. RESULTS: We included 102 eyes with AMD and 46 control eyes. Multivariable analysis revealed that older age (p\&lt;0.0001), advanced AMD stage (p\&lt;0.0001) and reduced retinal thickness (p\&lt;0.0001) were associated with decreased mean retinal sensitivity. No associations were found between choroidal thickness and retinal sensitivity within the macula. Within the 10{\textdegree} diameter circle of the macula, the presence of ellipsoid disruption, subretinal fluid, atrophy and fibrosis, and outer retinal tubulation on OCT images was also associated with decreased retinal sensitivity (all p\&lt;0.05). CONCLUSIONS: There is an association between TRS as determined by MAIA microperimetry and several OCT structural parameters across various stages of AMD. This study highlights the relevance of microperimetry as a functional outcome measure for AMD.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-313316},
	author = {Roh, Miin and La{\'\i}ns, In{\^e}s and Shin, Hyun Joon and Park, Dong Ho and Mach, Steven and Vavvas, Demetrios G and Kim, Ivana K and Miller, Joan W and Husain, Deeba and Miller, John B}
}
@article {1263396,
	title = {Complications Assoicated with MIRAgel for Treatment of Retinal Detachment},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 16},
	pages = {1-6},
	abstract = {MIRAgel (MIRA, Waltham, MA) is a hydrogel buckle that was introduced in 1979 as a new scleral implant for the treatment of retinal detachment. Long-term follow-up of more than 10\&nbsp;years revealed that the hydrolysis of the synthetic hydrophilic material leads to marked expansion of the substance, causing complications such as buckle extrusion and intrusion, eye motility disorder, cosmetic deformities, and periocular infections. Removal of the implant is the treatment of choice in cases with complications, but it is technically difficult due to the friability of the implant, severe scleral ectasia, and relatively high rate of redetachment after removal.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353822},
	author = {Roh, Miin and Lee, Nahyoung Grace and Miller, John B}
}
@article {1364533,
	title = {Etanercept, a widely used inhibitor of tumor necrosis factor-α (TNF-α), prevents retinal ganglion cell loss in a rat model of glaucoma},
	journal = {PLoS One},
	volume = {7},
	number = {7},
	year = {2012},
	month = {2012},
	pages = {e40065},
	abstract = {BACKGROUND: Visual loss in glaucoma is associated with pathological changes in retinal ganglion cell (RGC) axons and a slow decline in the RGC population. Age and elevated intraocular pressure (IOP) are the main risk factors for glaucomatous loss of vision. Several studies have implicated the proinflammatory cytokine tumor necrosis factor-α (TNF-α) as a link between elevated IOP and RGC death, but the cellular source of TNF-α and its causative role in RGC death remain uncertain. Here, using a rat model of glaucoma, we investigated the source of elevated TNF-α and examined whether Etanercept, a TNF-α blocker that is in common clinical use for other indications, is protective against RGC death. METHODOLOGY/PRINCIPAL FINDINGS: Episcleral vein cauterization (EVC) caused intraocular pressure (IOP) to be elevated for at least 28 days. IOP elevation resulted in a dramatic increase in TNF-α levels within a few days, axonal degeneration, and a 38\% loss of RGCs by 4 weeks. Immunostaining coupled with confocal microscopy showed that OHT induced robust induction of TNF-α in Iba-1-positive microglia around the optic nerve head (ONH). Despite persistent elevation of IOP, Etanercept reduced microglial activation, TNF-α levels, axon degeneration in the optic nerve, and the loss of RGCs. CONCLUSIONS/SIGNIFICANCE: Ocular hypertension (OHT) triggers an inflammatory response characterized by the appearance of activated microglia around the ONH that express TNF-α. Blocking TNF-α activity with a clinically approved agent inhibits this microglial response and prevents axonal degeneration and loss of RGCs. These findings suggest a new treatment strategy for glaucoma using TNF-α antagonists or suppressors of inflammation.},
	keywords = {Animals, Cell Death, Cell Survival, Disease Models, Animal, Etanercept, Glaucoma, Immunoglobulin G, Intraocular Pressure, Male, Ocular Hypertension, Rats, Receptors, Tumor Necrosis Factor, Retinal Ganglion Cells, Tumor Necrosis Factor-alpha},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0040065},
	author = {Roh, Miin and Zhang, Yan and Murakami, Yusuke and Thanos, Aristomenis and Lee, Sung Chul and Vavvas, Demetrios G and Benowitz, Larry I and Miller, Joan W}
}
@article {1538342,
	title = {Subthreshold Exudative Choroidal Neovascularization Associated With Age-Related Macular Degeneration Identified by Optical Coherence Tomography Angiography},
	journal = {J Vitreoretin Dis},
	volume = {4},
	number = {5},
	year = {2020},
	month = {2020 Oct},
	pages = {377-385},
	abstract = {Purpose: This article describes the clinical and multimodal imaging characteristics of subthreshold exudative choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). Methods: Among 3773 patients with AMD, 8 eyes (6 patients) were identified with the clinical phenotype of interest. Dilated fundus examinations, color fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were performed. Results: OCT typically showed a moderately reflective irregular pigment epithelial detachment with overlying subretinal fluid (SRF). Traditional FA did not show leakage and ICGA showed no definitive neovascular network or hot spots. However, OCTA clearly demonstrated a CNV within the pigment epithelial detachment. The majority of our cases (7 of 8) did not receive antivascular endothelial growth factor (anti-VEGF) injections, and visual acuity remained stable over the available follow-up period of I to 10 years. Conclusions: CNV is often associated with SRF and vision loss in AMD, usually requiring frequent anti-VEGF injections. OCTA allowed us to better identify CNV not readily detected on FA and ICGA. Although some have suggested early clinical intervention with anti-VEGF injections in any case with fluid and confirmed CNV on OCTA, we describe a subset of AMD patients with SRF who may be better managed by observation. These cases may represent a more indolent, mature, and stable vascular network.},
	issn = {2474-1264},
	doi = {10.1177/2474126420916607},
	author = {Roh, Miin and Miller, Joan W and Jeng-Miller, Karen W and Wang, Jay C and La{\'\i}ns, In{\^e}s and Silverman, Rebecca F and Loewenstein, John I and Husain, Deeba and Vavvas, Demetrios G and Miller, John B}
}
@article {1661599,
	title = {Cardiovascular and Mortality Risk with Intravitreal Vascular Endothelial Growth Factor Inhibitors in Patients with Diabetic Retinopathy},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {12},
	year = {2022},
	month = {2022 Dec},
	pages = {1145-1153},
	abstract = {OBJECTIVE: To investigate the cardiovascular (CV) safety associated with intravitreal anti-VEGF injections (IAVIs) in patients with diabetic retinopathy (DR). DESIGN: Population-based cohort study using Medicare and 2 commercial insurance claims databases in the United States from January 2009 to December\&nbsp;2017. SUBJECTS: Patients with DR aged >= 18 years in whom treatment with either IVAIs or laser procedure or intravitreal steroid injections was initiated. METHODS: We estimated the propensity score (PS) using multivariable logistic regression models, including 85 baseline covariates and PS-matched patients in a 1:1 ratio. We estimated the pooled hazard ratios (HRs) and 95\% confidence intervals (CIs). Subgroup analyses based on prior history of CV events were also conducted. MAIN OUTCOME MEASURES: A composite CV outcome of myocardial infarction (MI) or stroke, its individual components, and all-cause mortality in 180 and 365 days after treatment initiation. RESULTS: We identified 61 508 PS-matched patients in a 1:1 ratio in whom either IVAIs or laser or steroid treatment was initiated. Compared with laser or steroid treatment, IAVIs were not associated with an increased risk of the composite CV outcome (HR, 0.95; 95\% CI, 0.83-1.09), MI (HR, 0.93; 95\% CI, 0.76-1.13), or stroke (HR, 0.98; 95\% CI, 0.80-1.19) or the risk of all-cause mortality (HR, 1.25; 95\% CI, 0.97-1.62) at 180 days of follow-up. At 365 days, the risk of the composite CV outcome, stroke, and MI remained similar between the 2 groups, although the risk of all-cause mortality was increased with IAVIs (HR, 1.35; 95\% CI, 1.14-1.60). The subgroup analysis showed that the risk of all-cause mortality was increased in patients with a prior history of CV events. CONCLUSIONS: Among \&gt; 60 000 patients with DR, those who received IAVIs had a risk of CV events similar to those who received laser or steroid treatment. However, the risk of all-cause mortality was higher in patients who received IAVIs for DR.},
	keywords = {Cohort Studies, Diabetes Mellitus, Diabetic Retinopathy, Humans, Steroids, Stroke, United States, Vascular Endothelial Growth Factor A},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.06.010},
	author = {Roh, Miin and Tesfaye, Helen and Kim, Seoyoung C and Zabotka, Luke E and Patorno, Elisabetta}
}
@article {1318875,
	title = {Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration},
	journal = {PLoS One},
	volume = {13},
	number = {5},
	year = {2018},
	month = {2018},
	pages = {e0196481},
	abstract = {PURPOSE: Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. METHODS: We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. RESULTS: Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95\% CI-0.37 to -0.12, p\&lt;0.001 and β = 0.35, 95\% CI 0.25 to 0.46, p\&lt;0.001) and socioemontional functioning scale (β = -0.2, 95\% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95\% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95\% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95\% CI -0.03 to 0.16, p = 0.50, respectively). CONCLUSION: In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0196481},
	author = {Roh, Miin and Selivanova, Alexandra and Shin, Hyun Joon and Miller, Joan W and Jackson, Mary Lou}
}
@article {1789201,
	title = {Response to the Comment on "Evaluating the Diagnostic Accuracy and Management Recommendations of ChatGpt in Uveitis"},
	journal = {Ocul Immunol Inflamm},
	year = {2023},
	month = {2023 Dec 22},
	pages = {1-2},
	issn = {1744-5078},
	doi = {10.1080/09273948.2023.2293924},
	author = {Rojas-Carabali, William and Cifuentes-Gonz{\'a}lez, Carlos and Wei, Xin and Putera, Ikhwanuliman and Sen, Alok and Thng, Zheng Xian and Agrawal, Rajdeep and Tobias Elze and Sobrin, Lucia and Kempen, John H and Lee, Bernett and Biswas, Jyotirmay and Nguyen, Quan Dong and Gupta, Vishali and de-la-Torre, Alejandra and Agrawal, Rupesh}
}
@article {1773541,
	title = {Chatbots Vs. Human Experts: Evaluating Diagnostic Performance of Chatbots in Uveitis and the Perspectives on AI Adoption in Ophthalmology},
	journal = {Ocul Immunol Inflamm},
	year = {2023},
	month = {2023 Oct 13},
	pages = {1-8},
	abstract = {PURPOSE: To assess the diagnostic performance of two chatbots, ChatGPT and Glass, in uveitis diagnosis compared to renowned uveitis specialists, and evaluate clinicians{\textquoteright} perception about utilizing artificial intelligence (AI) in ophthalmology practice. METHODS: Six cases were presented to uveitis experts, ChatGPT (version 3.5 and 4.0) and Glass 1.0, and diagnostic accuracy was analyzed. Additionally, a survey about the emotions, confidence in utilizing AI-based tools, and the likelihood of incorporating such tools in clinical practice was done. RESULTS: Uveitis experts accurately diagnosed all cases (100\%), while ChatGPT achieved a diagnostic success rate of 66\% and Glass 1.0 achieved 33\%. Most attendees felt excited or optimistic about utilizing AI in ophthalmology practice. Older age and high level of education were positively correlated with increased inclination to adopt AI-based tools. CONCLUSIONS: ChatGPT demonstrated promising diagnostic capabilities in uveitis cases and ophthalmologist showed enthusiasm for the integration of AI into clinical practice.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2023.2266730},
	author = {Rojas-Carabali, William and Sen, Alok and Agarwal, Aniruddha and Tan, Gavin and Cheung, Carol Y and Rousselot, Andres and Agrawal, Rajdeep and Liu, Renee and Cifuentes-Gonz{\'a}lez, Carlos and Tobias Elze and Kempen, John H and Sobrin, Lucia and Nguyen, Quan Dong and de-la-Torre, Alejandra and Lee, Bernett and Gupta, Vishali and Agrawal, Rupesh}
}
@article {1789091,
	title = {Vitamin D deficiency and non-infectious uveitis: A systematic review and Meta-analysis},
	journal = {Autoimmun Rev},
	volume = {23},
	number = {2},
	year = {2023},
	month = {2023 Dec 03},
	pages = {103497},
	abstract = {BACKGROUND: Vitamin D plays a critical role in immunomodulation, and its deficiency is implicated in the pathogenesis of several autoimmune diseases. Nevertheless, its relationship with non-infectious uveitis (NIU), an inflammatory ocular disorder, remains inconclusive. METHODS: A systematic search was conducted in three databases from database inception until May 8, 2023, to investigate the potential relationship between vitamin D deficiency and NIU. We included observational studies reporting the measurement of vitamin D levels in patients with NIU and healthy controls without restriction of language or date of publication. Three pairs of authors independently screened the title and abstracts for potential eligibility and then in full text. A third author resolved disagreements. Three pairs of independent reviewers abstracted the data from the fully reviewed records and evaluated the risk of bias. We followed The MOOSE and PRISMA guidelines. Random effects meta-analyses were used for primary analysis. Studies not included in the meta-analysis were summarized descriptively. This review was registered in PROSPERO: CRD42022308105. FINDINGS: Of 933 records screened, 11 studies were included, and five were meta-analyzed, encompassing 354 cases and 5728 controls (mean participant age ranging from 7.1 to 58.9\&nbsp;years). Patients with vitamin D deficiency exhibited an Odds Ratio of 2.04 (95\% CI\&nbsp;=\&nbsp;1.55-2.68, P\&nbsp;\&lt;\&nbsp;0.00001) for developing NIU compared to controls. Overall, potential sources of bias were low across most studies. INTERPRETATION: Our findings suggest that vitamin D may play an essential role in the pathophysiology of NIU. While the included studies demonstrated generally low potential bias, additional rigorous prospective studies are necessary to confirm these findings and further elucidate the underlying mechanisms involved. Vitamin D supplementation could represent a possible therapeutic strategy for preventing or managing NIU if substantiated. Clinicians should consider screening for and addressing vitamin D deficiency in patients with or at risk for NIU.},
	issn = {1873-0183},
	doi = {10.1016/j.autrev.2023.103497},
	author = {Rojas-Carabali, William and Pineda-Sierra, Juan Sebasti{\'a}n and Cifuentes-Gonz{\'a}lez, Carlos and Morales, Mar{\'\i}a Sof{\'\i}a and Mu{\~n}oz-Vargas, Paula Tatiana and Pe{\~n}a-Pulgar, Luisa Fernanda and Fonseca-Mora, Mar{\'\i}a Alejandra and Cruz, Danna Lesley and Putera, Ikhwanuliman and Sobrin, Lucia and Agrawal, Rupesh and de-la-Torre, Alejandra}
}
@article {1761886,
	title = {Evaluating the Diagnostic Accuracy and Management Recommendations of ChatGPT in Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2023},
	month = {2023 Sep 18},
	pages = {1-6},
	abstract = {INTRODUCTION: Accurate diagnosis and timely management are vital for favorable uveitis outcomes. Artificial Intelligence (AI) holds promise in medical decision-making, particularly in ophthalmology. Yet, the diagnostic precision and management advice from AI-based uveitis chatbots lack assessment. METHODS: We appraised diagnostic accuracy and management suggestions of an AI-based chatbot, ChatGPT, versus five uveitis-trained ophthalmologists, using 25 standard cases aligned with new Uveitis Nomenclature guidelines. Participants predicted likely diagnoses, two differentials, and next management steps. Comparative success rates were computed. RESULTS: Ophthalmologists excelled (60-92\%) in likely diagnosis, exceeding AI (60\%). Considering fully and partially accurate diagnoses, ophthalmologists achieved 76-100\% success; AI attained 72\%. Despite an 8\% AI improvement, its overall performance lagged. Ophthalmologists and AI agreed on diagnosis in 48\% cases, with 91.6\% exhibiting concurrence in management plans. CONCLUSIONS: The study underscores AI chatbots{\textquoteright} potential in uveitis diagnosis and management, indicating their value in reducing diagnostic errors. Further research is essential to enhance AI chatbot precision in diagnosis and recommendations.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2023.2253471},
	author = {Rojas-Carabali, William and Cifuentes-Gonz{\'a}lez, Carlos and Wei, Xin and Putera, Ikhwanuliman and Sen, Alok and Thng, Zheng Xian and Agrawal, Rajdeep and Tobias Elze and Sobrin, Lucia and Kempen, John H and Lee, Bernett and Biswas, Jyotirmay and Nguyen, Quan Dong and Gupta, Vishali and de-la-Torre, Alejandra and Agrawal, Rupesh}
}
@article {1626104,
	title = {Effect of Autologous Serum Eye Drops on Corneal Haze after Corneal Cross-linking},
	journal = {Optom Vis Sci},
	volume = {99},
	number = {2},
	year = {2022},
	month = {2022 Feb 01},
	pages = {95-100},
	abstract = {SIGNIFICANCE: Corneal haze remains a frequent post-operative finding in patients undergoing corneal cross-linking. It has been shown that autologous serum tears promote epithelial healing and reduce post-operative pain; however, the role in the prevention of corneal haze has not been reported. PURPOSE: This study aimed to compare the effect of autologous serum tears versus preservative-free artificial tears on the prevention and resolution of post-cross-linking corneal haze. METHODS: A retrospective cohort study was conducted in a sample population from one surgeon at a tertiary eye center from 2016 to 2019. Seventy-six eyes of consecutive patients who underwent cross-linking were included. Records were reviewed for corneal Scheimpflug densitometry values and maximum keratometry, epithelial healing time, and the use of either autologous serum tears or preservative-free artificial tears. Corneal densitometry values, expressed in standardized grayscale units (GSU), were recorded for the anterior 150-μm corneal stroma and in the 0.0 to 2.0 mm and 2.0 to 6.0 mm zones. RESULTS: Forty-four eyes received autologous serum tears, whereas 32 eyes received preservative-free artificial tears. The baseline GSU of the anterior stromal 0 to 2 mm annulus and the 2 to 6 mm annulus did not significantly differ between groups (P = .50 and P = .40, respectively). There was a statistically significant increase in mean GSU for both anterior 0 to 2 mm and 2 to 6 mm zones between baseline and 1 month (P \&lt; .001) and 3 months (P \&lt; .001). When comparing the two groups, no statistically significant difference was found post-operatively between the mean GSU at 1 month for the anterior 0 to 2 mm (P = .38) nor the 2 to 6 mm zone (P = .12), or for the third month (P = .60 and P = .44, respectively). CONCLUSIONS: Using Scheimpflug densitometry, we did not find a significant difference in the post-cross-linking corneal haze at 1 and 3 post-operative months between patients who use autologous serum tears and those who use preservative-free artificial tears.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001839},
	author = {Roldan, Ana M and De Arrigunaga, Sofia and Ciolino, Joseph B}
}
@article {1623346,
	title = {Corneal Endothelial Transplantation in Uveitis: Incidence and Risk Factors},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 Nov 12},
	abstract = {PURPOSE: To estimate the incidence of corneal endothelial transplantation and identify risk factors among patients with non-infectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with non-infectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of corneal endothelial transplantation (CET), including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet Membrane Endothelial Keratoplasty procedures. The incidence of CET was calculated; potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis with a median follow-up 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10\% (95\% CI, 0.68\%-1.53\%). Risk factors for CET included age \&gt;60 years vs. \&lt;40 years (aHR 16.5; 95\% CI,4.70-57.9), anterior uveitis and scleritis vs. other types (aHR 2.97; 95\% CI, 1.46-6.05 and aHR 4.14; 95\% CI,1.28-13.4, respectively), topical corticosteroid treatment (aHR 2.84; 95\% CI, 1.32-6.13), cataract surgery (aHR 4.44; 95\% CI, 1.73-11.4), tube shunt surgery (aHR 11.9; 95\% CI, 5.30-26.8), band keratopathy (aHR 5.12; 95\% CI, 2.34-11.2), and hypotony (aHR 7.38; 95\% CI, 3.14-17.4). Duration of uveitis, trabeculectomy, PAS, and ocular hypertension had no significant association after multivariate adjustment. CONCLUSIONS: In patients with ocular inflammation, CET occurred infrequently. Tube shunt surgery, hypotony, band keratopathy, cataract surgery, and anterior segment inflammation were associated with increased risk of undergoing corneal endothelial transplantation; these factors likely are associated with endothelial cell damage.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.10.031},
	author = {Roldan, Ana M and Zebardast, Nazlee and Pistilli, Maxwell and Khachatryan, Naira and Payal, Abhishek and Begum, Hosne and Artornsombudh, Pichaporn and Pujari, Siddharth S and Rosenbaum, James T and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Bhatt, Nirali P and Foster, C Stephen and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Buchanich, Jeanine M and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study Research Group}
}
@article {1806586,
	title = {Expanded field: filling the gap between macula and widefield},
	journal = {Eye (Lond)},
	year = {2024},
	month = {2024 Feb 21},
	issn = {1476-5454},
	doi = {10.1038/s41433-024-02978-6},
	author = {Romano, Francesco and Ding, Xinyi and Miller, John B}
}
@article {1698231,
	title = {Combined or sequential DMEK in cases of cataract and Fuchs endothelial corneal dystrophy-A systematic review and meta-analysis},
	journal = {Acta Ophthalmol},
	volume = {102},
	number = {1},
	year = {2024},
	month = {2024 Feb},
	pages = {e22-e30},
	abstract = {To compare the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed after phacoemulsification and intraocular lens (IOL) implantation (sequential DMEK) and DMEK combined with phacoemulsification and IOL implantation (combined DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD) and cataract. Systematic literature review and meta-analysis performed according to the PRISMA guidelines and registered in PROSPERO. Literature searches were conducted in Medline and Scopus. Comparative studies reporting sequential DMEK and combined DMEK in FECD patients were included. The main outcome measure of the study was the corrected distance visual acuity (CDVA) improvement. Secondary outcomes were postoperative endothelial cell density (ECD), rebubbling rate and primary graft failure rate. Bias risk was assessed and a quality appraisal of the body of evidence was completed using the Cochrane Robin-I tool. A total of 667 eyes (5 studies) were included in this review, 292 eyes (43.77\%) underwent a combined DMEK, while 375 (56.22\%) eyes underwent a sequential DMEK surgery. We found no evidence of a difference between the two groups (mean difference, 95\% CI) regarding: (1) CDVA improvement (-0.06; -0.14, 0.03 LogMAR; 3 studies, I2 : 0\%; p = 0.86); (2) postoperative ECD (-62; -190, 67 cells/mm2 ; 4 studies, I2 : 67\%; p = 0.35); (3) rebubbling (risks ratio: 1.04; 0.59, 1.85; 4 studies, I2 : 48\%; p = 0.89); and primary graft failure rate (risks ratio: 0.91; 0.32, 2.57; 3 studies, I2 : 0\%; p = 0.86). Of all the 5 non-randomized studies, all (100\%) were graded as low quality. The overall quality of the analysed studies was low. Randomized controlled trials are needed to confirm no difference or superiority of one approach in terms of CDVA, endothelial cell count and postoperative complication rate between the two arms.},
	keywords = {Cataract, Cell Count, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies},
	issn = {1755-3768},
	doi = {10.1111/aos.15691},
	author = {Romano, Vito and Passaro, Maria Laura and Bachmann, Bjoern and Baydoun, Lamis and Ni Dhubhghaill, Sorcha and Dickman, Mor and Levis, Hannah J and Parekh, Mohit and Rodriguez-Calvo-De-Mora, Marina and Costagliola, Ciro and Virgili, Gianni and Semeraro, Francesco}
}
@article {1773446,
	title = {CORRELATION BETWEEN MICROPERIMETRY AND IMAGING IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE},
	journal = {Retina},
	volume = {44},
	number = {2},
	year = {2024},
	month = {2024 Feb 01},
	pages = {246-254},
	abstract = {PURPOSE: To determine the correlation between microperimetry and imaging findings in extensive macular atrophy with pseudodrusen-like appearance (EMAP). METHODS: This cross-sectional, observational study included 44 consecutive patients with EMAP (88 eyes) and 30 healthy subjects (60 eyes). Both groups underwent visual acuity assessment, mesopic and scotopic microperimetry, fundus photography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. Retinal sensitivity was also subdivided in macular (0-4{\textdegree}) and paramacular areas (8-10{\textdegree}). Scotopic sensitivity loss was defined as the difference between scotopic and mesopic sensitivities for each tested point. Eyes with EMAP were further classified into the three stages described by Romano et al: 19 eyes in Stage 1, 31 in Stage 2, and 38 in Stage 3. RESULTS: Mesopic and scotopic retinal sensitivity were significantly reduced in patients with EMAP compared with controls, particularly in the macular area (all P \&lt; 0.001). Mesopic retinal sensitivity progressively declined in more advanced EMAP stages (all P \&lt; 0.01), but no scotopic differences were observed between Stages 2 and 3 ( P = 0.08). Remarkably, scotopic sensitivity loss was significantly higher in Stage 1 ( P \&lt; 0.05).On multivariate analysis, mesopic dysfunction was associated with larger atrophic areas ( P \&lt; 0.01), foveal involvement ( P = 0.03), and fibrosis ( P = 0.02). Conversely, no independent variable was associated with a reduced scotopic retinal sensitivity (all P \&gt; 0.05). CONCLUSION: The findings highlight that patients with EMAP suffer from a severe cone- and rod-mediated dysfunction on microperimetry. The predominant rod impairment in the early cases (Stage 1) emphasizes the importance of dark-adapted scotopic microperimetry as a clinical end point and suggests defective transportation across the RPE-Bruch membrane complex in its pathogenesis.},
	keywords = {Atrophy, Cross-Sectional Studies, Humans, Macular Degeneration, Retina, Tomography, Optical Coherence, Visual Field Tests},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003951},
	author = {Romano, Francesco and Boon, Camiel J F and Invernizzi, Alessandro and Bosello, Francesca and Casati, Stefano and Zaffalon, Chiara and Riva, Ester and Bertoni, Alice Ingrid and Agarwal, Aniruddha and Kalra, Gagan and Cozzi, Mariano and Staurenghi, Giovanni and Salvetti, Anna Paola}
}
@article {1688236,
	title = {Incidence and management of early postoperative complications in lamellar corneal transplantation},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {261},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {3097-3111},
	abstract = {PURPOSE: To provide a comprehensive review of the incidence, risk factors, and management of early complications after deep anterior lamellar keratoplasty (DALK), Descemet stripping automated keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A literature review of complications, that can occur from the time of the transplant up to 1\&nbsp;month after the transplant procedure, was conducted. Case reports and case series were included in the review. RESULTS: Complications in the earliest postoperative days following anterior and posterior lamellar keratoplasty have shown to affect graft survival. These complications include, but are not limited to, double anterior chamber, sclerokeratitis endothelial graft detachment, acute glaucoma, fluid misdirection syndrome, donor-transmitted and recurrent infection, and Uretts-Zavalia syndrome. CONCLUSION: It is essential for surgeons and clinicians to not only be aware of these complications but also know how to manage them to minimize their impact on long-term transplant survival and visual outcomes.},
	issn = {1435-702X},
	doi = {10.1007/s00417-023-06073-6},
	author = {Romano, Davide and Aiello, Francesco and Parekh, Mohit and Levis, Hannah J and Gadhvi, Kunal A and Moramarco, Antonio and Viola, Pietro and Fontana, Luigi and Semeraro, Francesco and Romano, Vito}
}
@article {1798301,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {131},
	number = {4},
	year = {2024},
	month = {2024 Apr},
	pages = {e15-e16},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.11.029},
	author = {Romano, Francesco and Zaffalon, Chiara and Staurenghi, Giovanni and Salvetti, Anna Paola}
}
@article {1782251,
	title = {Hyperreflective Ganglion Cell Layer Band in Choroideremia},
	journal = {Retina},
	year = {2023},
	month = {2023 Nov 08},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000004003},
	author = {Romano, Francesco and Barbieri, Lucrezia and Staurenghi, Giovanni and Salvetti, Anna Paola}
}
@article {1782221,
	title = {Clinical, Genotypic and Imaging Characterization of the spectrum of ABCA4 Retinopathies},
	journal = {Ophthalmol Retina},
	year = {2023},
	month = {2023 Nov 02},
	abstract = {PURPOSE: To investigate the clinical and genotypic differences in the spectrum of ABCA4-associated retinopathies (ABCA4R). DESIGN: Observational, cross-sectional case series. PARTICIPANTS: Sixty-six patients (132 eyes) carrying biallelic ABCA4 variants. METHODS: Patients underwent visual acuity measurement and multimodal imaging. Clinical records were reviewed for age at onset, presenting symptoms, genetic variants, and electroretinogram (ERG). Each eye was assigned to a phenotype based on age at onset, imaging and ERG: cone dystrophy-bull{\textquoteright}s eye maculopathy (CD-BEM, 40 eyes), cone-rod dystrophy (CRD, 12 eyes), Stargardt disease (SD, 28 eyes), late-onset SD (LO-SD, 38 eyes), fundus flavimaculatus (FFM, 14 eyes). Images were analyzed for: peripapillary sparing, retinal pigment epithelium (RPE) atrophy (definitely decreased autofluorescence, DDAF), flecks patterns using autofluorescence; type of atrophy according to CAM reports, macular and choroidal thickness on optical coherence tomography (OCT); choriocapillaris flow deficits on OCT angiography. MAIN OUTCOME MEASURES: Primary outcome was to report the demographic, genotypic and imaging characteristics of the different ABCA4R phenotypes. Secondary objectives included the assessment of imaging biomarkers as outcome measures for clinical trials. RESULTS: Age at onset was lower in CRD (12{\textpm}8 years) and higher in LO-SD patients (59{\textpm}9 years) (all p\&lt;0.01). Central vision loss was a common presenting symptom in CD-BEM and SD, whereas LO-SD patients primarily complained of difficult dark adaptation. Missense variants were more frequent in CD-BEM, and splice site in CRD and LO-SD (p\&lt;0.05). Peripapillary sparing was absent in three eyes with LO-SD (8\%). CD-BEM eyes typically had cORA alterations (98\%), while CRD and SD eyes showed both cORA and cRORA (71-100\%). LO-SD patients had larger areas of DDAF (100\% cRORA) and of choriocapillaris flow deficits (all p\&lt;0.01). Repeatability of DDAF measurements was low for some phenotypes (CD-BEM and CRD) and atrophic areas \&lt;7.5 mm2. Resorbed flecks were significantly associated with CRD and LO-SD (p\&lt;0.01). CONCLUSIONS: This research provides a thorough evaluation of the spectrum of ABCA4R. Our findings suggest that certain phenotypes show preferential photoreceptor degeneration (e.g., CD-BEM), while others have substantial RPE and choriocapillaris alterations (e.g., LO-SD). We recommend that clinical trial endpoints take into consideration these imaging features to improve the interpretation of their results.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.10.023},
	author = {Romano, Francesco and Lamanna, Francesca and Boon, Camiel J F and Siligato, Alessandro and Kalra, Gagan and Agarwal, Aniruddha and Medori, Chiara and Bertelli, Matteo and Pellegrini, Marco and Invernizzi, Alessandro and Staurenghi, Giovanni and Salvetti, Anna Paola}
}
@article {1798326,
	title = {Quality assurance in corneal transplants: Donor cornea assessment and oversight},
	journal = {Surv Ophthalmol},
	year = {2024},
	month = {2024 Jan 08},
	abstract = {The cornea is the most frequently transplanted human tissue, and corneal transplantation represents the most successful allogeneic transplant worldwide. In order to obtain good surgical outcome and visual rehabilitation and to ensure the safety of the recipient, accurate screening of donors and donor tissues is necessary throughout the process. This mitigates the risks of transmission to the recipient, including infectious diseases and environmental contaminants, and ensures high optical and functional quality of the tissues. The process can be divided into 3 stages: (1) donor evaluation and selection before tissue harvest performed by the retrieval team, (2) tissue analysis during the storage phase conducted by the eye bank technicians after the retrieval, and, (3) tissue quality checks undertaken by the surgeons in the operating room before transplantation. Although process improvements over the years have greatly enhanced safety, quality, and outcome of the corneal transplants, a lack of standardization between centers during certain phases of the process still remains, and may impact on the quality and number of transplanted corneas. Here we detail the donor screening process for the retrieval teams, eye bank operators. and ophthalmic surgeons and examine the limitations associated with each of these stages.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2023.12.002},
	author = {Romano, Vito and Passaro, Maria Laura and Ruzza, Alessandro and Parekh, Mohit and Airaldi, Matteo and Levis, Hannah J and Ferrari, Stefano and Costagliola, Ciro and Semeraro, Francesco and Ponzin, Diego}
}
@article {1806621,
	title = {Double trouble in DMEK surgery: Learning experience and review of the literature},
	journal = {Eur J Ophthalmol},
	year = {2024},
	month = {2024 Feb 22},
	pages = {11206721241228346},
	abstract = {PURPOSE: To report a challenging Descemet Membrane Endothelial Keratoplasty (DMEK) case, complicated by intraoperative aqueous misdirection and spontaneous anterior chamber fibrin reaction. METHODS: A 70-year-old female affected by corneal edema due to Fuchs endothelial dystrophy underwent a triple procedure (cataract extraction - IOL implantation - DMEK surgery) in her left eye. This report illustrates the management of the intraoperative complications of aqueous misdirection syndrome and anterior chamber fibrin reaction. RESULTS: Despite the optimal management of the posterior pressure and the thorough removal of the fibrinous reaction during the case, the DMEK graft was not completely unfolded and centred at the end of the surgical procedure. Nonetheless, the patient showed good long-term anatomical and functional recovery: at the last follow-up (2 years after surgery), central corneal thickness was 526 {\textmu}m with a best corrected visual acuity of 20/25 and an endothelial cell density of 1112 cell/mm2. CONCLUSION: Early recognition and prompt management of intraoperative aqueous misdirection syndrome and anterior chamber fibrin reaction during DMEK surgery is essential to ensure good functional and anatomical outcomes.},
	issn = {1724-6016},
	doi = {10.1177/11206721241228346},
	author = {Romano, Vito and Passaro, Maria Laura and Airaldi, Matteo and Ancona, Chiara and Pagano, Luca and Semeraro, Francesco and Pineda, Roberto}
}
@article {1470979,
	title = {Multimodal imaging features of intraocular foreign bodies},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Oct 14},
	pages = {1-15},
	abstract = {: To determine the imaging approach for evaluating intraocular foreign bodies (IOFBs) by comparing the ability of different modalities [plain film x-ray, computed tomography (CT), magnetic resonsance imaging (MRI), convetional ultrasound, and ultrasound biomicroscopy] to detect and characterize IOFBs. : Systematic review of the literature. : CT is the most practical first step for evaluating patients with suspected IOFBs because it can detect a wide range of IOFB types at small limitis of detection. MRI and ultrasound are best reserved as adjunctive tests in most cases although these tests may provide important insights especially with wood, plastic, and glass IOFBs. Imaging characteristics of metal, wood, glass, plastic, stone, concrete, and graphite IOFBs are reviewed. : Understanding the limits of detection for each IOFB type and imaging modality as well as the characteristic features of different IOFBs is of paramount importance to optimizing the management of ocular trauma patients.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1674894},
	author = {Rong, Andrew J and Fan, Kenneth C and Golshani, Behrad and Bobinski, Matthew and McGahan, John P and Eliott, Dean and Morse, Lawrence S and Modjtahedi, Bobeck S}
}
@article {1125381,
	title = {Genetic associations for keratoconus: a systematic review and meta-analysis},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Jul 04},
	pages = {4620},
	abstract = {Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95\% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 {\texttimes} 10(-11)), RXRA-COL5A1 (rs1536482, P = 2.5 {\texttimes} 10(-9)), FNDC3B (rs4894535, P = 1.4 {\texttimes} 10(-8)), IMMP2L (rs757219, P = 6.1 {\texttimes} 10(-7); rs214884, P = 2.3 {\texttimes} 10(-5)), and BANP-ZNF469 (rs9938149, P = 1.3 {\texttimes} 10(-5)). The gene COL4A4 (rs2229813, P = 1.3 {\texttimes} 10(-12); rs2228557, P = 4.5 {\texttimes} 10(-7)) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value \&lt; 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-04393-2},
	author = {Rong, Shi Song and Ma, Sarah Tsz Ue and Yu, Xin Ting and Ma, Li and Chu, Wai Kit and Chan, Tommy Chung Yan and Wang, Yu Meng and Young, Alvin L and Pang, Chi Pui and Jhanji, Vishal and Chen, Li Jia}
}
@article {1435414,
	title = {Comorbidity of dementia and age-related macular degeneration calls for clinical awareness: a meta-analysis},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {1777-1783},
	abstract = {AIM: To determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis. METHODS: We searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case-control and cohort studies that evaluated the association of dementia/Alzheimer{\textquoteright}s disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95\% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases. RESULTS: Among 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (p<=0.017, OR>=1.24, I<=9\%) or AD (p=0.001, OR=2.22, I=50\%) were at risk for AMD, particularly for late AMD (p\&lt;0.001, OR=1.37, I=0). AMD was also significantly associated with increased risk of AD/cognitive impairment (p=0.037, OR=2.42, I=38\%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p\&lt;0.001, I<=79\%) and Trail Making Test A (p\&lt;0.001, I=0). Sensitivity analysis and Egger{\textquoteright}s test indicated our results were less likely biased. CONCLUSIONS: A significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-313277},
	author = {Rong, Shi Song and Lee, Bo Yee and Kuk, Andrew K and Yu, Xin Ting and Li, Suki S and Li, Jian and Guo, Yanjun and Yin, Yilin and Osterbur, David L and Yam, Jason C S and Cheung, Carol Y and Chen, Li Jia and Wong, Tien Y and Ng, Danny Siu-Chun}
}
@article {1667706,
	title = {Phenotypic and Genetic Links between Body Fat Measurements and Primary Open-Angle Glaucoma},
	journal = {Int J Mol Sci},
	volume = {24},
	number = {4},
	year = {2023},
	month = {2023 Feb 15},
	abstract = {The phenotypic and genetic links between body fat phenotypes and primary open-angle glaucoma (POAG) are unclear. We conducted a meta-analysis of relevant longitudinal epidemiological studies to evaluate the phenotypic link. To identify genetic links, we performed genetic correlation analysis and pleiotropy analysis of genome-wide association study summary statistics datasets of POAG, intraocular pressure (IOP), vertical cup-to-disc ratio, obesity, body mass index (BMI), and waist-to-hip ratio. In the meta-analysis, we first established that obese and underweight populations have a significantly higher risk of POAG using longitudinal data. We also discovered positive genetic correlations between POAG and BMI and obesity phenotypes. Finally, we identified over 20 genomic loci jointly associated with POAG/IOP and BMI. Among them, the genes loci CADM2, RP3-335N17.2, RP11-793K1.1, RPS17P5, and CASC20 showed the lowest false discovery rate. These findings support the connection between body fat phenotypes and POAG. The newly identified genomic loci and genes render further functional investigation.},
	keywords = {Genome-Wide Association Study, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Obesity, Phenotype},
	issn = {1422-0067},
	doi = {10.3390/ijms24043925},
	author = {Rong, Shi Song and Yu, Xin Ting}
}
@article {1430536,
	title = {Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese},
	journal = {Exp Eye Res},
	volume = {180},
	year = {2019},
	month = {2019 Mar},
	pages = {129-136},
	abstract = {The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (P = 4.3 {\texttimes} 10, OR = 0.72, I = 0). Additionally, we replicated the association of one known SNP, rs33912345 (P = 0.0061, OR = 0.69, I = 45\%), with POAG in the Chinese cohorts but not in the Japanese cohort (P \&gt; 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (P = 0.017, OR = 0.70, I = 53\%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (P\&lt;0.005). Furthermore, two haplotypes, C-C (P = 1.13 {\texttimes} 10, OR = 1.41, I = 0) and A-A (P = 0.045, OR = 0.68, I = 70\%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.12.014},
	author = {Rong, Shi Song and Lu, Shi Yao and Matsushita, Kenji and Huang, Chukai and Leung, Christopher K S and Kawashima, Rumi and Usui, Shinichi and Tam, Pancy O S and Young, Alvin L and Tsujikawa, Motokazu and Zhang, Mingzhi and Nishida, Kohji and Wiggs, Janey L and Tham, Clement C and Pang, Chi Pui and Chen, Li Jia}
}
@article {1059811,
	title = {Early Performance on an Eye Surgery Simulator Predicts Subsequent Resident Surgical Performance},
	journal = {J Surg Educ},
	year = {2017},
	month = {2017 Apr 20},
	abstract = {OBJECTIVE: To examine early performance on an eye surgery simulator and its relationship to subsequent live surgical performance in a single large residency program. DESIGN: Retrospective study. SETTING: Massachusetts Eye and Ear, Harvard Medical School, Department of Ophthalmology. METHODS: In a retrospective study, we compared performance of 30 first-year ophthalmology residents on an eye surgery simulator to their surgical skills as third-year residents. Variables collected from the eye surgery simulator included scores on the following modules of the simulator (Eyesi, VRmagic, Mannheim, Germany): antitremor training level 1, bimanual training level 1, capsulorhexis level 1 (configured), forceps training level 1, and navigation training level 1. Subsequent surgical performance was assessed using the total number of phacoemulsification cataract surgery cases for each resident, as well as the number performed as surgeon during residency and scores on global rating assessment of skills in intraocular surgery (GRASIS) scales during the third year of residency. Spearman correlation coefficients were calculated between each of the simulator performance and subsequent surgical performance variables. We also compared variables in a small group of residents who needed extra help in learning cataract surgery to the other residents in the study. MAIN OUTCOME MEASURES: Relationships between Eyesi scores early in residency and surgical performance measures in the final year of residency. RESULTS: A total of 30 residents had Eyesi data from their first year of residency and had already graduated so that all subsequent surgical performance data were available. There was a significant correlation between capsulorhexis task score on the simulator and total surgeries (r = 0.745, p = 0.008). There was a significant correlation between antitremor training level 1 (r = 0.554, p = 0.040), and forceps training level 1 (r = 0.622, p = 0.023) with primary surgery numbers. There was a significant correlation between forceps training level 1 (r = 0.811, p = 0.002), and navigation training level 1 (r = 0.692, p =0.013) with total GRASIS score. There was a significant inverse correlation between total GRASIS score and residents in need of extra help (r = -0.358, p =0.003). CONCLUSION: Module scores on an eye surgery simulator early in residency may predict a resident׳s future performance in the operating room. These scores may allow early identification of residents in need of supplemental training in cataract surgery.},
	issn = {1878-7452},
	doi = {10.1016/j.jsurg.2017.04.002},
	author = {Roohipoor, Ramak and Yaseri, Mehdi and Teymourpour, Amir and Kloek, Carolyn and Miller, John B and Loewenstein, John I}
}
@article {688641,
	title = {Retinopathy of prematurity screening criteria in Iran: new screening guidelines.},
	journal = {Arch Dis Child Fetal Neonatal Ed},
	volume = {101},
	number = {4},
	year = {2016},
	month = {2016 Jul},
	pages = {F288-93},
	abstract = {OBJECTIVE: To test the applicability of existing retinopathy of prematurity (ROP) guidelines on Iranian patients and to develop novel ROP screening criteria in Iran. METHODS: Both eyes of 1932 infants born <=37 weeks of gestation and/or weighting <=3000 g were included in this prospective cohort study that was conducted across nine neonatal intensive care units and a tertiary eye hospital ROP clinic. The patients were examined for ROP and the need for treatment (type 1 ROP or worse). All the patients were screened 4 weeks after birth or at 31 weeks of postmenstrual age, whichever was later. The patients were followed until retinal vascularisation was completed or the patients reached 50 weeks of gestational age (GA) without prethreshold ROP. A receiver operating characteristic curve was used to determine the best screening criteria for ROP. Screening criteria from other countries were applied to our patient data to determine their ability to appropriately detect ROP. MAIN OUTCOME MEASURE: Patients with ROP requiring treatment. RESULTS: The mean GA{\textpm}SD and birth weight (BW){\textpm}SD of the screened patients were 32{\textpm}2.7 weeks and 1713{\textpm}516 g, respectively. Using criteria of GA<=32 weeks or BW <=2000 yielded sensitivity and specificity of 100\% and 26.7\%, respectively, for treatment requiring ROP regardless of clinical comorbidities. Using screening recommendations of American Academy of Pediatrics would miss 25.4\% of ROP and 8.4\%ROP requiring treatment in our cohort. CONCLUSIONS: Other countries screening recommendations would result in a significant amount of missed cases of treatment requiring ROP when applied to Iran. As a result, we have proposed new guidelines for premature babies in Iran.},
	issn = {1468-2052},
	doi = {10.1136/archdischild-2015-309137},
	author = {Roohipoor, Ramak and Karkhaneh, Reza and Farahani, Afsar and Ebrahimiadib, Nazanin and Modjtahedi, Bobeck and Fotouhi, Akbar and Yaseri, Mehdi and Khodabande, Alireza and Zarei, Mohammad and Imani Fuladi, Marjan and Taheri, Arash and Riazi Esfahani, Mohammad and Loewenstein, John}
}
@article {1430537,
	title = {Evaluation of computer-based retinopathy of prematurity (ROP) education for ophthalmology residents: a randomized, controlled, multicenter study},
	journal = {J AAPOS},
	year = {2019},
	month = {2019 Mar 15},
	abstract = {PURPOSE: To evaluate the effect of a computer-based training program-Massachusetts Eye \&amp; Ear ROP Trainer-on residents{\textquoteright} knowledge of retinopathy of prematurity (ROP) management. METHODS: In this prospective, randomized study, ophthalmology residents from nine different training programs consented to participate. Those who completed the study were randomly assigned to either the Trainer or the control group. The ROP Trainer was created using clinical cases encompassing the stages of ROP in digital pictures and videos. It includes sections on screening decisions, examination techniques, and diagnosis, and a reference section with the expert video clips and a searchable image library. Subjects in the control group were asked to study standard print material on ROP. A pre- and post-test, consisting of theoretical and practical (diagnosis) questions, and a post-intervention satisfaction test were administered. Accuracy of ROP diagnosis was assessed. RESULTS: A total of 180 residents agreed to participate, of whom 60 completed the study. Residents in the Trainer group had statistically significant improvements (P = 0.003) in ROP knowledge and diagnostic ability (P = 0.005). Residents randomized to the Trainer group were more satisfied with the training materials than were those in the control group. There was no significant difference in improving knowledge by year of training, sex, or country. Considering all training levels, a statistically significant increase was observed in sensitivity for the diagnosis of preplus or worse, zone I or II, ROP stage, category, and aggressive posterior ROP in the Trainer group. CONCLUSIONS: In this study, the Trainer was shown to significantly improve ROP knowledge and diagnostic skills of residents, regardless of sex, year, of training, or country.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2018.11.008},
	author = {Roohipoor, Ramak and Alvarez, Rodrigo and Brodowska, Katarzyna and Yaseri, Mehdi and Kloek, Carolyn and Riazi, Mohamad and Nourinia, Ramin and Nikkhah, Homayoun and Prajna, N Venkatesh and Krishnan, Chandrasekharan and Tuli, Sonal and Green, Laura and Srikumaran, Divya and Shah, Ankoor S and Mantagos, Iason S and Chiang, Michael and Chan, R V Paul and Loewenstein, John}
}
@article {1439861,
	title = {Correction: Loss of PGC-1α in RPE induces mesenchymal transition and promotes retinal degeneration},
	journal = {Life Sci Alliance},
	volume = {2},
	number = {3},
	year = {2019},
	month = {2019 Jun},
	issn = {2575-1077},
	doi = {10.26508/lsa.201900436},
	author = {Rosales, Mariana Aparecida Brunini and Shu, Daisy Y and Iacovelli, Jared and Saint-Geniez, Magali}
}
@article {1439862,
	title = {Loss of PGC-1α in RPE induces mesenchymal transition and promotes retinal degeneration},
	journal = {Life Sci Alliance},
	volume = {2},
	number = {3},
	year = {2019},
	month = {2019 Jun},
	abstract = {The retinal pigment epithelium (RPE) supports visual processing and photoreceptor homeostasis via energetically demanding cellular functions. Here, we describe the consequences of repressing peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α), a master regulator of mitochondrial function and biogenesis, on RPE epithelial integrity. The sustained silencing of PGC-1α in differentiating human RPE cells affected mitochondria/autophagy function, redox state, and impaired energy sensor activity ultimately inducing epithelial to mesenchymal transition (EMT). Adult conditional knockout of PGC-1 coactivators in mice resulted in rapid RPE dysfunction and transdifferentiation associated with severe photoreceptor degeneration. RPE anomalies were characteristic of autophagic defect and mesenchymal transition comparable with the ones observed in age-related macular degeneration. These findings demonstrate that PGC-1α is required to maintain the functional and phenotypic status of RPE by supporting the cells{\textquoteright} oxidative metabolism and autophagy-mediated repression of EMT.},
	issn = {2575-1077},
	doi = {10.26508/lsa.201800212},
	author = {Rosales, Mariana Aparecida Brunini and Shu, Daisy Y and Iacovelli, Jared and Saint-Geniez, Magali}
}
@article {1363194,
	title = {A Study into the Evolutionary Divergence of the Core Promoter Elements of PRPF31 and TFPT},
	journal = {J Mol Genet Med},
	volume = {7},
	number = {2},
	year = {2013},
	month = {2013 Aug},
	abstract = {Mutations in have been implicated in retinitis pigmentosa, a blinding disease caused by degeneration of rod photoreceptors. The disease mechanism in the majority of cases is haploinsufficiency. Crucially, attempts at generation of animal models of disease have proved unsuccessful, yielding animals with a visual phenotype that does not mirror human disease. This suggests that, in these animals, the transcriptional regulation of is different to humans and compared to other species. Study of the evolution of the core promoter has important implications for our understanding of human disease, as disease phenotype is modified by differentially expressed alleles in the population. lies in a head-to-head arrangement with , a gene involved in cellular apoptosis. The two genes were shown to share common regulatory elements in the human genome. In this study, the core promoters of and were characterised by dual-luciferase reporter assay using genomic DNA from the green monkey, domestic dog and house mouse. It was found that the core promoters were conserved between human and monkey. In dog, the core promoter was conserved, but different gene architecture meant the gene was controlled by a long-range promoter lying some 2000bp from the transcription start site. There was very low level of conservation (\&lt;20\%) of the 5{\textquoteright} region between mouse and human. It was shown that mouse populations did not show variable expression levels, revealing a potential explanation for the lack of phenotype observed in the knock-out mouse model.},
	issn = {1747-0862},
	doi = {10.4172/1747-0862.1000067},
	author = {Rose, Anna M and Shah, Amna Z and Alfano, Giovanna and Bujakowska, Kinga M and Barker, Amy F and Robertson, J Louis and Rahman, Sufia and S{\'a}nchez, Lourdes Vald{\'e}s and Diaz-Corrales, Francisco J and Chakarova, Christina F and Krishna, Abhay and Bhattacharya, Shomi S}
}
@article {1478346,
	title = {New observations and emerging ideas in diagnosis and management of non-infectious uveitis: A review},
	journal = {Semin Arthritis Rheum},
	volume = {49},
	number = {3},
	year = {2019},
	month = {2019 Dec},
	pages = {438-445},
	abstract = {BACKGROUND: Non-infectious uveitis (NIU) is an immune-mediated disease with clinical symptoms such as eye pain, redness, floaters, and light sensitivity. NIU is one of the leading causes of preventable blindness. OBJECTIVE: This review describes current and emerging therapies for NIU. METHODS: PubMed searches were conducted using the terms uveitis, therapy, corticosteroids, immunomodulators, biologics, intravitreal injections, intraocular implants, and adverse events deemed relevant if they presented data relating to prevalence, diagnosis, and treatment of uveitis. RESULTS: Diagnosis and management of NIU may require collaboration among different healthcare providers, including ophthalmologists and rheumatologists. Although many patients with NIU respond to corticosteroid (CS) therapy, long-term CS use can be associated with potentially severe adverse events. Localized CS therapies have been developed to reduce adverse events; however, some intravitreal injections and intraocular implants were linked to elevated intraocular pressure and cataracts. CS-sparing therapies such as biologics have demonstrated efficacy and safety while reducing CS burden. Biologics targeting tumor necrosis factor provide CS-sparing options for patients with NIU. Additional studies are needed to address long-term efficacy and safety of biologics targeting IL-6 and inhibitors of JAK/STAT. CONCLUSION: Biologics, JAK/STAT inhibitors, and improved localized therapies may provide additional options for patients with NIU.},
	issn = {1532-866X},
	doi = {10.1016/j.semarthrit.2019.06.004},
	author = {Rosenbaum, James T and Bodaghi, Bahram and Couto, Cristobal and Zierhut, Manfred and Acharya, Nisha and Pavesio, Carlos and Tay-Kearney, Mei-Ling and Neri, Piergiorgio and Douglas, Kevin and Pathai, Sophia and Song, Alexandra P and Kron, Martina and Foster, C Stephen}
}
@article {1773616,
	title = {Proptosis Regression After Teprotumumab Treatment for Thyroid Eye Disease},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2023},
	month = {2023 Oct 04},
	abstract = {PURPOSE: This study analyzed the degree and timing of proptosis regression after teprotumumab therapy. METHODS: A retrospective study of all patients who completed 8 teprotumumab infusions at 1 institution from January 1, 2020 to December 31, 2022. Change in proptosis was assessed in millimeters and percentages compared with immediate post-treatment and pretreatment proptosis. RESULTS: Of 119 patients with post-treatment data (mean follow-up 10.56 months, range: 3.05-25.08), 208 (87.39\%) eyes of 110 patients had initial proptosis improvement. Of the 78 patients with multiple follow-up visits, 102 (65.38\%) eyes of 59 patients had proptosis regression averaging 12.78\% (range: 1.85-58.82\%) compared with immediately post-treatment or 2.43 mm (0.5-10.0 mm). Eight (7.84\%) eyes had initial documentation of regression more than 1 year after treatment, 40 (39.22\%) between 6 months and 1 year, and 54 (52.94\%) eyes within 6 months with 25 (46.30\%) of these continuing to worsen at subsequent follow-up. Forty (25.64\%) eyes of 24 patients had more proptosis at most recent follow-up than before teprotumumab, with an average regression of 1.53 mm (0.5-4.0 mm) or 7.74\% (1.85-20.69\%) of pretreatment proptosis. In comparison, 99 (63.46\%) eyes of 54 patients maintained improvement, with reduction averaging 3.13 mm (0.5-11.0 mm) or 13.19\% (1.92-41.67\%) of pretreatment proptosis (p \&lt; 0.001). CONCLUSIONS: Two-thirds of eyes had regression despite initial teprotumumab response, typically within 1 year of treatment, with ongoing worsening over time. Most patients maintained some proptosis reduction compared with before treatment despite regression, although 25\% were worse than pretreatment. The occurrence of regression was independent of the pretreatment duration of clinical thyroid eye disease. Overall, compared with preteprotumumab, there was a greater amount of improvement than regression at most recent follow-up.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002531},
	author = {Rosenblatt, Tatiana R and Chiou, Carolina A and Yoon, Michael K and Wolkow, Natalie and Lee, Nahyoung Grace and Freitag, Suzanne K}
}
@article {1586139,
	title = {Key factors in a rigorous longitudinal image-based assessment of retinopathy of prematurity},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Mar 08},
	pages = {5369},
	abstract = {To describe a database of longitudinally graded telemedicine retinal images to be used as a comparator for future studies assessing grader recall bias and ability to detect typical progression (e.g. International Classification of Retinopathy of Prematurity (ICROP) stages) as well as incremental changes in retinopathy of prematurity (ROP). Cohort comprised of retinal images from 84 eyes of 42 patients who were sequentially screened for ROP over 6 consecutive weeks in a telemedicine program and then followed to vascular maturation or treatment, and then disease stabilization. De-identified retinal images across the 6 weekly exams (2520 total images) were graded by an ROP expert based on whether ROP had improved, worsened, or stayed the same compared to the prior week{\textquoteright}s images, corresponding to an overall clinical "gestalt" score. Subsequently, we examined which parameters might have influenced the examiner{\textquoteright}s ability to detect longitudinal change; images were graded by the same ROP expert by image view (central, inferior, nasal, superior, temporal) and by retinal components (vascular tortuosity, vascular dilation, stage, hemorrhage, vessel growth), again determining if each particular retinal component or ROP in each image view had improved, worsened, or stayed the same compared to the prior week{\textquoteright}s images. Agreement between gestalt scores and view, component, and component by view scores was assessed using percent agreement, absolute agreement, and Cohen{\textquoteright}s weighted kappa statistic to determine if any of the hypothesized image features correlated with the ability to predict ROP disease trajectory in patients. The central view showed substantial agreement with gestalt scores (κ = 0.63), with moderate agreement in the remaining views. Of retinal components, vascular tortuosity showed the most overall agreement with gestalt (κ = 0.42-0.61), with only slight to fair agreement for all other components. This is a well-defined ROP database graded by one expert in a real-world setting in a masked fashion that correlated with the actual (remote in time) exams and known outcomes. This provides a foundation for subsequent study of telemedicine{\textquoteright}s ability to longitudinally assess ROP disease trajectory, as well as for potential artificial intelligence approaches to retinal image grading, in order to expand patient access to timely, accurate ROP screening.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-84723-7},
	author = {Rosenblatt, Tatiana R and Ji, Marco H and Vail, Daniel and Ludwig, Cassie A and Al-Moujahed, Ahmad and Pasricha, Malini Veerappan and Callaway, Natalia F and Kumm, Jochen and Moshfeghi, Darius M}
}
@article {1608574,
	title = {Fall risk in patients with pseudophakic monovision},
	journal = {Can J Ophthalmol},
	volume = {58},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {11-17},
	abstract = {OBJECTIVE: Vision changes can precipitate falls in the elderly resulting in significant morbidity and mortality. We hypothesized that pseudophakic monovision and ensuing anisometropia and aniseikonia impact elderly fall risk. This study assessed fall risk in patients with pseudophakic monovision, pseudophakic single vision distance (classic cataract surgery), and cataracts with no surgery. DESIGN: Retrospective single-institution cohort study PARTICIPANTS: Patients with bilateral cataracts diagnosed at 60 years of age or older who underwent bilateral cataract surgery (monovision or single vision distance) or did not undergo any cataract surgery (n = 13 385). Patients with unilateral surgery or a fall prior to cataract diagnosis were excluded. METHODS: Data were obtained from the Stanford Research Repository. Time-to-fall analysis was performed across all 3 groups. Primary outcome was hazard ratio (HR) for fall after second eye cataract surgery or after bilateral cataract diagnosis. RESULTS: Of 13 385 patients (241 pseudophakic monovision, 2809 pseudophakic single vision, 10 335 no surgery), 850 fell after cataract diagnosis. Pseudophakic monovision was not associated with fall risk after controlling for age, sex, and myopia. Pseudophakic single-vision patients had a decreased time to fall compared with no-surgery patients (log rank, p \&lt; 0.001). Older age at cataract diagnosis (HR =1.05, 95\% confidence interval [CI] 1.04-1.06, p \&lt; 0.001) or at time of surgery (HR = 1.05, 95\% CI 1.03-1.07, p \&lt; 0.001) increased fall risk, as did female sex (HR = 1.29, 95\% CI 1.10-1.51, p = 0.002) and preexisting myopia (HR = 1.31, 95\% CI 1.01-1.71, p = 0.046) among nonsurgical patients. CONCLUSIONS: Pseudophakic monovision did not impact fall risk, but pseudophakic single vision may increase falls compared with patients without cataract surgery.},
	keywords = {Aged, Cataract, Cataract Extraction, Female, Humans, Lens Implantation, Intraocular, Myopia, Pseudophakia, Retrospective Studies, Visual Acuity},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2021.07.010},
	author = {Rosenblatt, Tatiana R and Vail, Daniel and Ludwig, Cassie A and Al-Moujahed, Ahmad and Pasricha, Malini Veerappan and Ji, Marco H and Callaway, Natalia F and Moshfeghi, Darius M}
}
@article {705126,
	title = {Pupillary sign of aberrant regeneration of the third nerve.},
	journal = {Neurology},
	volume = {86},
	number = {18},
	year = {2016},
	month = {2016 May 3},
	pages = {1746},
	issn = {1526-632X},
	doi = {10.1212/WNL.0000000000002642},
	author = {Rosenvald, Olga R and Lessell, Simmons}
}
@article {1470994,
	title = {Topical sustained drug delivery to the retina with a drug-eluting contact lens},
	journal = {Biomaterials},
	volume = {217},
	year = {2019},
	month = {2019 Oct},
	pages = {119285},
	abstract = {Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug{\textquoteright}s residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.},
	issn = {1878-5905},
	doi = {10.1016/j.biomaterials.2019.119285},
	author = {Ross, Amy E and Bengani, Lokendrakumar C and Tulsan, Rehka and Maidana, Daniel E and Salvador-Culla, Borja and Kobashi, Hidenaga and Kolovou, Paraskevi E and Zhai, Hualei and Taghizadeh, Koli and Kuang, Liangju and Mehta, Manisha and Vavvas, Demetrios G and Kohane, Daniel S and Ciolino, Joseph B}
}
@article {1532329,
	title = {Fibrotic Changes and Endothelial-to-Mesenchymal Transition Promoted by VEGFR2 Antagonism Alter the Therapeutic Effects of VEGFA Pathway Blockage in a Mouse Model of Choroidal Neovascularization},
	journal = {Cells},
	volume = {9},
	number = {9},
	year = {2020},
	month = {2020 Sep 09},
	abstract = {Many patients with wet age-related macular degeneration do not respond well to anti- vascular endothelial growth factor A (VEGFA) therapy for choroidal neovascularization (CNV), and the efficacy of anti-VEGFA decreases over time. We investigated the hypothesis that fibrotic changes, in particular via endothelial-to-mesenchymal transition (EndoMT), play a role in CNV and alter the therapeutic effects of VEGFA pathway blockage. Induction of EndoMT of primary human retinal endothelial cells led to a significantly reduced response to VEGFA at the level of gene expression, cellular proliferation, migration, and tube formation. Suppression of EndoMT restored cell responsiveness to VEGFA. In a mouse model of spontaneous CNV, fibrotic changes and EndoMT persisted as the CNV lesions became more established over time. VEGFA receptor-2 (VEGFR2) antagonism further induced fibrosis and EndoMT in the CNV. The combination of VEGFR2 antagonism and fibrosis/EndoMT inhibition was more effective than either individual treatment in reducing CNV. Our data indicate that fibrosis and EndoMT are involved in the progression of CNV, are exacerbated by VEGFR2 inhibition, and could provide an explanation for the reduced efficacy of anti-VEGFA treatment over time.},
	issn = {2073-4409},
	doi = {10.3390/cells9092057},
	author = {Rossato, Franco Aparecido and Su, Yu and Mackey, Ashley and Ng, Yin Shan Eric}
}
@article {1125386,
	title = {Neonatal Assessment Visual European Grid (NAVEG): Unveiling neurological risk},
	journal = {Infant Behav Dev},
	volume = {49},
	year = {2017},
	month = {2017 Jul 05},
	pages = {21-30},
	issn = {1934-8800},
	doi = {10.1016/j.infbeh.2017.06.002},
	author = {Rossi, Andrea and Gnesi, Marco and Montomoli, Cristina and Chirico, Gaetano and Malerba, Laura and Merabet, Lotfi B and NAVEG Study Group and Fazzi, Elisa}
}
@article {1732551,
	title = {The Pleiotropy of Complement Factor H},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {8},
	year = {2023},
	month = {2023 Aug 01},
	pages = {745-746},
	keywords = {Complement Factor H, Humans, Mutation, Phenotype},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.2756},
	author = {Rossin, Elizabeth J and Sobrin, Lucia}
}
@article {1580496,
	title = {Single-cell RNA sequencing: An overview for the ophthalmologist},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {191-197},
	abstract = {Understanding the molecular composition of pathogenic tissues is a critical step in understanding the pathophysiology of disease and designing therapeutics. First described in 2009, single cell RNA sequencing (scRNAseq) is a methodology whereby thousands of cells are simultaneously isolated into individual micro-environments that can be altered experimentally and the genome-wide RNA expression of each cell is captured. It has undergone significant technological improvement over the last decade and gained tremendous popularity. scRNAseq is an improvement over prior pooled RNA analyses which cannot identify the cellular composition and heterogeneity of a tissue of interest. This new approach offers new opportunity for new discovery, as tissue samples can now be sub-categorized into groups of cell types based on genome-wide gene expression in an unbiased fashion. As ophthalmologists, we are uniquely positioned to obtain pathologic samples from the eye for further study. ScRNAseq has already been applied in ophthalmology to characterize retinal tissue, and it may offer the key to understanding various pathological processes in the future.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1889615},
	author = {Rossin, Elizabeth J and Sobrin, Lucia and Kim, Leo A}
}
@article {1549027,
	title = {Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study},
	journal = {Ophthalmol Retina},
	volume = {5},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {805-814},
	abstract = {PURPOSE: To describe the clinical characteristics, surgical outcomes, and management recommendations in patients with traumatic rhegmatogenous retinal detachment (RRD) resulting from self-injurious behavior (SIB). DESIGN: International, multicenter, retrospective, interventional case series. PARTICIPANTS: Patients with SIB from 23 centers with RRD in at least 1 eye. METHODS: Clinical histories, preoperative assessment, surgical details, postoperative management, behavioral intervention, and follow-up examination findings were reviewed. MAIN OUTCOME MEASURES: The rate of single-surgery anatomic success (SSAS) was the primary outcome. Other outcomes included new RRD in formerly attached eyes, final retinal reattachment, and final visual acuity. RESULTS: One hundred seven eyes with RRDs were included from 78 patients. Fifty-four percent of patients had bilateral RRD or phthisis bulbi in the fellow eye at final follow-up. The most common systemic diagnoses were autism spectrum disorder (35.9\%) and trisomy 21 (21.8\%) and the most common behavior was face hitting (74.4\%). The average follow-up time was 3.3 {\textpm} 2.8 years, and surgical outcomes for operable eyes were restricted to patients with at least 3 months of follow-up (81 eyes). Primary initial surgeries were vitrectomy alone (33.3\%), primary scleral buckle (SB; 26.9\%), and vitrectomy with SB (39.7\%), and 5 prophylactic SBs were placed. Twenty-three eyes (21.5\%) with RRDs were inoperable. The SSAS was 23.1\% without tamponade (37.2\% if including silicone oil), and final reattachment was attained in 80\% (36.3\% without silicone oil tamponade). Funnel-configured RRD (P\&nbsp;= 0.006) and the presence of grade C proliferative vitreoretinopathy (P\&nbsp;= 0.002) correlated with re-detachment. The use of an SB predicted the final attachment rate during the initial surgery (P = 0.005) or at any surgery (P\&nbsp;= 0.008. These associations held if restricting to 64 patients with >=12 months followup. Anatomic reattachment correlated with better visual acuity (P \&lt; 0.001). CONCLUSIONS: RRD resulting from SIB poses therapeutic challenges because of limited patient cooperation, bilateral involvement, chronicity, and ongoing trauma in vulnerable and neglected patients. The surgical success rates were some of the lowest in the modern retinal detachment literature. The use of an SB may result in better outcomes, and visual function can be restored in some patients.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2020.11.012},
	author = {Rossin, Elizabeth J and Tsui, Irena and Wong, Sui Chien and Hou, Kirk K and Prakhunhungsit, Supalert and Blair, Michael P and Shapiro, Michael J and Leishman, Lisa and Nagiel, Aaron and Lifton, Jacob A and Quiram, Polly and Ringeisen, Alexander L and Henderson, Robert H and Arruti, Natalia and Buzzacco, Dominic M and Kusaka, Shunji and Ferrone, Philip J and Belin, Peter J and Chang, Emmanuel and Hubschman, Jean-Pierre and Murray, Timothy G and Leung, Ella H and Wu, Wei-Chi and Olsen, Karl R and Harper, C Armitage and Rahmani, Safa and Goldstein, Jessica and Lee, Thomas and Nudleman, Eric and Cernichiaro-Espinosa, Linda A and Chhablani, Jay and Berrocal, Audina M and Yonekawa, Yoshihiro}
}
@article {1549031,
	title = {Factors Associated With Increased Risk of Serious Ocular Injury in the Setting of Orbital Fracture},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {1},
	year = {2021},
	month = {2021 Jan 01},
	pages = {77-83},
	abstract = {Importance: Orbital fractures are common in ocular trauma, and there is a need to develop predictive tools to estimate risk of concurrent ocular injury. Objective: To identify clinical and radiographic features that are associated with increased risk of substantial ocular injury in the setting of orbital fracture. Design, Setting, and Participants: Retrospective consecutive case series of patients who sustained orbital fractures between 2012 and 2018. Examinations were done at 1 of 2 level 1 trauma centers in the emergency or inpatient setting. A total of 430 consecutive patients (500 eyes) between 2012 and 2017 met inclusion criteria for the training sample. After building a predictive model, 88 additional consecutive patients (97 eyes) between 2017 and 2018 who met inclusion criteria were collected as a test sample. Main Outcomes and Measures: The primary outcome measure was substantial ocular injury distinct from orbital fracture. Results: The mean age of our patient population was 53.5 years (range, 16-100 years). The overall rate of substantial ocular injury was 20.4\%, and the rate of injury requiring immediate ophthalmic attention was 14.4\%. Five variables were found to be associated with increased risk of substantial ocular injury: blunt trauma with a foreign object (odds ratio [OR], 19.4; 95\% CI, 6.3-64.1; P \&lt; .001), inability to count fingers (OR, 10.1; 95\% CI, 2.8-41.1; P = .002), roof fracture (OR, 9.1; 95\% CI, 2.8-30.0; P = .002), diplopia on primary gaze (OR, 6.7; 95\% CI, 1.7-25.1; P = .003), and conjunctival hemorrhage or chemosis (OR, 4.2; 95\% CI, 2.2-8.5; P \&lt; .001). The results were translated into a bedside tool that was tested in an independent group of eyes (n = 97) and found to be associated with substantial ocular injury with a 95\% sensitivity (95\% CI, 77.2-99.9), 40\% specificity (95\% CI, 28.9-52.0), 31.8\% positive predictive value (95\% CI, 27.5-36.5), and 96.8\% negative predictive value (95\% CI, 81.3-99.5). Conclusions and Relevance: A minority of patients with an orbital fracture had a substantial ocular injury. Certain radiographic and clinical findings were associated with substantial ocular injury. Testing of the algorithm in prospective longitudinal settings appears warranted.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.5108},
	author = {Rossin, Elizabeth J and Szypko, Colleen and Giese, Isaiah and Hall, Nathan and Gardiner, Matthew F and Lorch, Alice}
}
@article {1483594,
	title = {Site of Origin of the Ophthalmic Artery Influences the Risk for Retinal Versus Cerebral Embolic Events},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {1},
	year = {2021},
	month = {2021 Mar 01},
	pages = {24-28},
	abstract = {BACKGROUND: Embolic events leading to retinal ischemia or cerebral ischemia share common risk factors; however, it has been well documented that the rate of concurrent cerebral infarction is higher in patients with a history of transient ischemic attack (TIA) than in those with monocular vision loss (MVL) due to retinal ischemia. Despite the fact that emboli to the ophthalmic artery (OA) and middle cerebral artery share the internal carotid artery (ICA) as a common origin or transit for emboli, the asymmetry in their final destination has not been fully explained. We hypothesize that the anatomic location of the OA takeoff from the ICA may contribute to the differential flow of small emboli to the retinal circulation vs the cerebral circulation. METHODS: We report a retrospective, comparative, case-control study on 28 patients with retinal ischemia and 26 patients with TIA or cerebral infarction caused by embolic events. All subjects underwent either computed tomography angiography or MRA. The location of the ipsilateral OA origin off the ICA was then graded in a blinded fashion and compared between cohorts. Vascular risk factors were collected for all patients, including age, sex, hypertension, hyperlipidemia, arrhythmia, diabetes, coronary artery disease, and smoking. RESULTS: We find that in patients with retinal ischemia of embolic etiology, the ipsilateral OA takeoff from the ICA is more proximal than in patients with cerebral infarcts or TIA (P = 0.0002). We found no statistically significant differences in demographic, vascular, or systemic risk factors. CONCLUSIONS: We find that the mean anatomical location of the OA takeoff from the ICA is significantly more proximal in patients with MVL due to retinal ischemia compared with patients with TIA or cerebral ischemia. This finding contributes significantly to our understanding of a long observed but poorly understood phenomenon that patients with MVL are less likely to have concurrent cerebral ischemia than are patients with TIA.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000883},
	author = {Rossin, Elizabeth J and Gilbert, Aubrey L and Koen, Nicholas and Leslie-Mazwi, Thabele M and Cunnane, Mary E and Rizzo, Joseph F}
}
@article {1698276,
	title = {Neuro-ophthalmic Complications in Pediatric Leukemia},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {4},
	year = {2023},
	month = {2023 Dec 01},
	pages = {520-524},
	abstract = {BACKGROUND: Optic neuropathy in childhood leukemia occurs through multiple direct and indirect mechanisms, including leukemic infiltration of the optic nerve, infection, blood dyscrasias, or adverse effects of treatment. We aimed to characterize visual outcomes in pediatric patients with leukemia-associated neuro-ophthalmic manifestations. METHODS: We retrospectively identified patients with leukemia and optic nerve pathology over 13 years by diagnostic billing codes. We collected information on demographics, presentation, treatment course, and visual outcomes directly from medical records. RESULTS: Of the 19 patients who met inclusion criteria, 17 (89.5\%) had pseudotumor cerebri and 2 had direct optic nerve infiltration. Causes of increased intracranial pressure included central nervous system infiltration (6 of 17), hyperviscosity/leukemia (2 of 17), venous sinus thrombosis (3 of 17), medication induced (5 of 17), and bacterial meningitis (1 of 17). 47.1\% (8 of 17) had papilledema at the time of leukemia diagnosis, and 94.1\% (16 of 17) of patients with pseudotumor cerebri were treated with acetazolamide. At presentation, 3 patients had decreased vision secondary to macular ischemia, subhyaloid vitreous hemorrhage, or steroid induced glaucoma. Following treatment of pseudotumor cerebri, binocular visual acuity was >=20/25 in all patients. One patient with optic nerve infiltration had a final visual acuity of count fingers in the affected eye. CONCLUSIONS: In our chart review, the most common mechanism of neuro-ophthalmic involvement in pediatric leukemia was elevated intracranial pressure from a myriad of causes. Visual outcomes from patients with elevated intracranial pressure were excellent. Understanding the mechanisms by which leukemia can cause optic nerve disease in pediatric patients can facilitate earlier diagnosis and treatment and potentially improve visual outcomes.},
	keywords = {Child, Eye, Humans, Leukemia, Optic Nerve Diseases, Papilledema, Pseudotumor Cerebri, Retrospective Studies},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001879},
	author = {Rothfield, Lindsay and Falcone, Michelle M and Gaier, Eric D and Heidary, Gena and Gise, Ryan}
}
@article {1626101,
	title = {American Glaucoma Society Position Paper: Information Sharing Using Established Standards is Essential to the Future of Glaucoma Care},
	journal = {Ophthalmol Glaucoma},
	year = {2021},
	month = {2021 Dec 18},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.12.002},
	author = {Rothman, Adam L and Chang, Robert and Kolomeyer, Natasha N and Turalba, Angela and Stein, Joshua D and Boland, Michael V}
}
@article {1603866,
	title = {Infiltrative Sebaceous Carcinoma Presenting as a "Tumor Tarsorrhaphy"},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {1},
	year = {2022},
	month = {2022 Jan-Feb 01},
	pages = {e35},
	keywords = {Adenocarcinoma, Sebaceous, Eyelids, Humans, Sebaceous Gland Neoplasms},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002014},
	author = {Rozanski, Collin and Stagner, Anna M and Lee, Nahyoung Grace}
}
@article {1615205,
	title = {Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options},
	journal = {Cells},
	volume = {10},
	number = {9},
	year = {2021},
	month = {2021 Sep 03},
	abstract = {In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.},
	issn = {2073-4409},
	doi = {10.3390/cells10092302},
	author = {Ruan, Yue and Jiang, Subao and Musayeva, Aytan and Pfeiffer, Norbert and Gericke, Adrian}
}
@article {1364534,
	title = {Axl is essential for VEGF-A-dependent activation of PI3K/Akt},
	journal = {EMBO J},
	volume = {31},
	number = {7},
	year = {2012},
	month = {2012 Apr 04},
	pages = {1692-703},
	abstract = {Herein, we report that vascular endothelial growth factor A (VEGF-A) engages the PI3K/Akt pathway by a previously unknown mechanism that involves three tyrosine kinases. Upon VEGF-A-dependent activation of VEGF receptor-2 (VEGFR-2), and subsequent TSAd-mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand-independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt. Other VEGF-A-mediated signalling pathways are independent of Axl. Interfering with Axl expression or function impairs VEGF-A- but not bFGF-dependent migration of endothelial cells. Similarly, Axl null mice respond poorly to VEGF-A-induced vascular permeability or angiogenesis, whereas other agonists induce a normal response. These results elucidate the mechanism by which VEGF-A activates PI3K/Akt, and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes.},
	keywords = {Amino Acid Motifs, Animals, Cell Movement, Endothelial Cells, Fibroblast Growth Factor 2, Mice, Mice, Knockout, Neovascularization, Physiologic, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptor Protein-Tyrosine Kinases, Signal Transduction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2},
	issn = {1460-2075},
	doi = {10.1038/emboj.2012.21},
	author = {Ruan, Guo-Xiang and Kazlauskas, Andrius}
}
@article {397856,
	title = {Screening of refractive surgery candidates for LASIK and PRK.},
	journal = {Cornea},
	volume = {34},
	number = {5},
	year = {2015},
	month = {2015 May},
	pages = {e13-4},
	keywords = {Cornea, Corneal Diseases, Female, Humans, Keratomileusis, Laser In Situ, Lasers, Excimer, Male, Photorefractive Keratectomy},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000415},
	author = {Rubinfeld, Roy S and Trattler, William B and Talamo, Jonathan and Majmudar, Parag and Lindstrom, Richard L}
}
@article {1593832,
	title = {The Effect of Sodium Iodide on Stromal Loading, Distribution and Degradation of Riboflavin in a Rabbit Model of Transepithelial Corneal Crosslinking},
	journal = {Clin Ophthalmol},
	volume = {15},
	year = {2021},
	month = {2021},
	pages = {1985-1994},
	abstract = {Purpose: To evaluate effects of sodium iodide (NaI) on riboflavin concentration in corneal stroma before and during ultraviolet A (UVA) light exposure using a novel transepithelial corneal collagen crosslinking (CXL) procedure (EpiSmart CXL system, CXL Ophthalmics, Encinitas CA). Methods: Riboflavin solutions with NaI (Ribostat, CXL Ophthalmics, Encinitas CA) and without NaI were used for CXL in rabbits using EpiSmart. A pilot study determined sufficient riboflavin loading time. Four rabbits were dosed and monitored. Riboflavin fluorescence intensity was assessed from masked slit-lamp photos. A 12 min loading time was selected. Sixteen additional rabbits received the two formulae in contralateral eyes for CXL. Riboflavin uptake was assessed at 0, 10, 15, 20, 25, and 30 min of UVA exposure using a scale for riboflavin fluorescence previously validated against stromal concentration. Post sacrifice, corneal stromal samples were analyzed for concentrations of riboflavin and riboflavin 5{\textquoteright}-phosphate. Results: Eyes dosed with NaI riboflavin had higher riboflavin grades compared to eyes dosed with the NaI-free riboflavin formulation immediately after riboflavin loading and persisting throughout UVA exposure, with significantly higher (P \&lt; 0.01 to \&lt; 0.05) riboflavin grades from 15 through 25 min of UVA exposure. Riboflavin grades decreased more slowly in eyes dosed with NaI riboflavin through 25 minutes of UVA exposure. Minor conjunctival irritation was noted with or without NaI. Conclusion: The addition of NaI to riboflavin solution is associated with increased riboflavin concentration in corneal stroma throughout a clinically relevant time course of UVA exposure. This effect may be a combination of enhanced epithelial penetration and reduced riboflavin photodegradation and should enhance intrastromal crosslinking.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S300886},
	author = {Rubinfeld, Roy S and Gum, Glenwood G and Talamo, Jonathan H and Parsons, Edward C}
}
@article {1307459,
	title = {Quantitative analysis of corneal stromal riboflavin concentration without epithelial removal},
	journal = {J Cataract Refract Surg},
	volume = {44},
	number = {2},
	year = {2018},
	month = {2018 Feb},
	pages = {237-242},
	abstract = {PURPOSE: To compare the corneal stromal riboflavin concentration and distribution using 2 transepithelial corneal crosslinking (CXL) systems. SETTING: Absorption Systems, San Diego, California, USA. DESIGN: Experimental study. METHODS: The stromal riboflavin concentration of 2 transepithelial CXL systems was compared in rabbit eyes in\&nbsp;vivo. The systems were the Paracel/Vibex Xtra, comprising riboflavin 0.25\% solution containing TRIS and ethylenediaminetetraacetic acid and an isotonic solution of riboflavin 0.25\%, (Group 1) and the CXLO system (Group 2). Manufacturers{\textquoteright} Instructions For Use were followed. The intensity of riboflavin fluorescence by slitlamp observation 10, 15, and 20\&nbsp;minutes after instillation was graded on a scale of 0 to 5. The animals were humanely killed and the corneal stromal samples analyzed with liquid chromatography and mass spectrometry. RESULTS: The mean riboflavin fluorescence intensity grades in\&nbsp;Group 1 (4 eyes) were 3.8, 4.8, and 4.8 at 10, 15, and 20\&nbsp;minutes, respectively. The mean grades in Group 2 (3 eyes) were 2.0, 2.3, and 2.0, respectively. The riboflavin distribution was uniform in Group 1 but not in Group 2. The mean riboflavin concentration by liquid chromatography and mass spectrometry was 27.0\&nbsp;μg/g stromal tissue in Group 1 and 6.7\&nbsp;μg/g in Group 2. A stromal riboflavin concentration theoretically adequate for CXL, 15\&nbsp;μg/g, was achieved in all eyes in Group 1 and no eyes\&nbsp;in Group 2. Slitlamp grading correlated well with liquid\&nbsp;chromatography and mass spectrometry concentration (R\&nbsp;=\&nbsp;0.940). CONCLUSIONS: The system used in Group 1 produced corneal riboflavin concentrations that were theoretically adequate for effective transepithelial CXL (>=15\&nbsp;μg/g), while the system in Group 2 did not. Slitlamp grading successfully estimated the corneal riboflavin concentration and can be used to ensure an adequate concentration of riboflavin in the cornea for transepithelial CXL.},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2018.01.010},
	author = {Rubinfeld, Roy S and Stulting, R Doyle and Gum, Glenwood G and Talamo, Jonathan H}
}
@article {1658677,
	title = {Characterising collateral vessels in eyes with branch retinal vein occlusions using widefield swept-source optical coherence tomography angiography},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {12},
	year = {2023},
	month = {2023 Nov 22},
	pages = {1887-1891},
	abstract = {BACKGROUND/AIMS: To characterise the morphology, location and functional significance of both macular and extramacular collateral vessels (CVs) in patients with a history of branch retinal vein occlusion (BRVO) using widefield swept-source optical coherence tomography angiography (WF SS OCTA). METHODS: Patients with a history of BRVO underwent WF SS OCTA testing to acquire 12{\texttimes}12 mm images, which were evaluated for CVs and non-perfusion area (NPA). Region of interest analysis of individual CVs was performed to identify correlations between CV size, depth and retinal location. Mixed effects multivariate regression analyses of factors associated with NPA and visual acuity (VA) were performed. RESULTS: Fifty-five CVs were identified in 28 BRVO eyes from 27 patients. CVs were identified in 42.9\% (12/28) of eyes with a history of BRVO, and of these, 45.5\% (25/55) were extramacular. The majority of CVs (87.3\%, 48/55) coursed through both the superficial and the deep capillary plexus (DCP), while a subset (12.7\%, 7/55) were strictly superficial. No CVs were found to course strictly through the DCP alone. CV depth increased with distance from the optic disc (p=0.011) and CV size increased with distance from the fovea (p=0.005). There were no statistically significant associations between CVs and NPA, or between CVs and VA. CONCLUSIONS: WF SS OCTA revealed that a large fraction of CVs that form after BRVO are extramacular, and the morphology of CVs varies as a function of retinal location. Depth-resolved study of CVs may offer valuable insights on the pathophysiological mechanisms leading to the development of macular oedema.},
	keywords = {Fluorescein Angiography, Fundus Oculi, Humans, Retinal Vein Occlusion, Retinal Vessels, Retrospective Studies, Tomography, Optical Coherence},
	issn = {1468-2079},
	doi = {10.1136/bjo-2021-320356},
	author = {Rudnick, Noam D and Vingopoulos, Filippos and Wang, Jay C and Garg, Itika and Cui, Ying and Zhu, Ying and Le, Rongrong and Katz, Raviv and Lu, Yifan and Patel, Nimesh A and Miller, John B}
}
@article {591216,
	title = {Visual Acuity Outcomes of the Boston Keratoprosthesis Type 1: Multicenter Study Results.},
	journal = {Am J Ophthalmol},
	volume = {162},
	year = {2016},
	month = {2016 Feb},
	pages = {89-98.e1},
	abstract = {PURPOSE: To report logarithm of the minimal angle of resolution (logMAR) visual outcomes of the Boston keratoprosthesis type 1. DESIGN: Prospective cohort study. METHODS: Preoperative, intraoperative, and postoperative parameters of 300 eyes of 300 patients who underwent implantation of a Boston keratoprosthesis type 1 device between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centers were collected. RESULTS: After an average of 17.1 {\textpm} 14.8\&nbsp;months, visual acuity improved significantly (P \&lt; .0001) to a mean final value of 0.89 {\textpm} 0.64 (20/150). There were also significantly fewer eyes with light perception (6.7\%; n\&nbsp;= 19; P \&lt; .0001), although 3.1\% (n\&nbsp;= 9) progressed to no light perception. There was no association between age (P\&nbsp;= .08), sex (P\&nbsp;= .959), operative side (P\&nbsp;= .167), or failure (P\&nbsp;= .494) and final visual acuity. The median time to achieve 20/200 visual acuity was 1\&nbsp;month (95\% confidence interval 1.0-6.0) and it was retained for an average of 47.8\&nbsp;months. Multivariate analysis, controlling for preoperative visual acuity, demonstrated 2 factors associated with final visual outcome: chemical injury was associated with better final vision (P\&nbsp;= .007), whereas age-related macular degeneration was associated with poorer vision (P \&lt; .0001). CONCLUSIONS: The Boston keratoprosthesis type 1 is an effective device for rehabilitation in advanced ocular surface disease, resulting in a significant improvement in visual acuity. Eyes achieved a mean value of 20/150 (0.89 {\textpm} 0.64 logMAR units) after 6\&nbsp;months and this was relatively stable thereafter. The best visual prognosis is observed in chemical injury eyes, whereas the\&nbsp;worst prognosis is in aniridia, although the latter has limited visual potential.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.10.023},
	author = {Rudnisky, Christopher J and Belin, Michael W and Guo, Rong and Ciolino, Joseph B and Boston Type 1 Keratoprosthesis Study Group}
}
@article {1632299,
	title = {Authors{\textquoteright} response: Lam D, Blah TR, Francis IC. Letter to the Editor regarding the publication: "The clinical and pathogenic spectrum of surgically-induced scleral necrosis"},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {6},
	year = {2022},
	month = {2022 Nov-Dec},
	pages = {1738-1740},
	keywords = {Humans, Necrosis, Sclera},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2022.01.013},
	author = {Ruiz-Lozano, Raul E and Garza-Garza, Lucas A and Davila-Cavazos, Osvaldo and Foster, C Stephen and Rodriguez-Garcia, Alejandro}
}
@article {1573096,
	title = {The clinical and pathogenic spectrum of surgically-induced scleral necrosis: A review},
	journal = {Surv Ophthalmol},
	volume = {66},
	number = {4},
	year = {2021},
	month = {2021 Jul-Aug},
	pages = {594-611},
	abstract = {The onset of scleral necrosis after ocular surgery may have catastrophic ocular and systemic consequences. The two most frequent surgeries causing surgically-induced scleral necrosis (SISN) are pterygium excision and cataract extraction. Several pathogenic mechanisms are involved in surgically induced scleral necrosis. All of them are poorly understood. Ocular trauma increasing lytic action of collagenases with subsequent collagen degradation, vascular disruption leading to local ischemia, and immune complex deposition activating the complement system represents some of the events that lead to scleral necrosis. The complex cascade of events involving different pathogenic mechanisms and the patient{\textquoteright}s abnormal immune response frequently leads to delayed wound healing that predisposes the development of scleral necrosis. The management of SISN ranges from short-term systemic anti-inflammatory drugs to aggressive immunosuppressive therapy and surgical repair. Therefore, before performing any ocular surgery involving the sclera, a thorough ophthalmic and systemic evaluation must be done to identify high-risk patients that may develop SISN.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2020.12.008},
	author = {Ruiz-Lozano, Raul E and Garza-Garza, Lucas A and Davila-Cavazos, Osvaldo and Foster, C Stephen and Rodriguez-Garcia, Alejandro}
}
@article {1677746,
	title = {Limited Clinical Value of Anti-Retinal Antibody Titers and Numbers in Autoimmune Retinopathy},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {749-755},
	abstract = {PURPOSE: To assess the possible correlation of anti-retinal antibody titers and number of anti-retinal antibodies with outcome measurements including visual acuity, subjective vision loss, visual field, and electroretinography in patients with autoimmune retinopathy. DESIGN: Single-center, retrospective cross-sectional study. PATIENTS AND METHODS: Patients with autoimmune retinopathy who underwent anti-retinal antibody testing at least twice during their follow-up were enrolled. Anti-retinal antibody titers and numbers were grouped as improved, stable, or worsened. Outcomes included Snellen visual acuity, patient-reported vision loss, Humphrey visual field mean deviations, and electroretinography parameters. RESULTS: Thirty-one eyes among 16 patients with autoimmune retinopathy were included. Between-group analyses of visual acuity, subjective vision loss, visual field, and electroretinography outcomes did not reveal any significant differences by anti-retinal antibody titer or number group at a 95\% confidence interval. CONCLUSION: Changes in anti-retinal antibody titers or numbers were not associated with any vision outcome. Repeated anti-retinal antibody testing may be unnecessary after diagnosis of autoimmune retinopathy and detection of an anti-retinal antibody.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S404826},
	author = {Rujkorakarn, Ploysai and Margolis, Michael J and Morvey, Diana and Zhou, Yujia and Foster, C Stephen}
}
@article {1664970,
	title = {Patient Perceptions of Retinal Detachment Management and Recovery through Social Media},
	journal = {Semin Ophthalmol},
	year = {2023},
	month = {2023 Jan 24},
	pages = {1-5},
	abstract = {PURPOSE: Social media support groups can provide accessibility to advice and emotional regarding medical topics, such as retinal detachment repair, but this is almost universally provided by laypersons. We sought to determine how topics related to retinal detachment repair are associated with various emotional responses and the spread of misinformation, as identified through an online social media support group. METHODS: Retrospective observational study of the largest Facebook support group for retinal detachment from 03/19/2021 to 07/19/2021. Members of the support group that posted during the study period. Comments were coded by content (Pre-procedural, Peri-procedural Post procedural, Repeat procedures) and participant response (Emotional responses, Asking for medical advice, and Misinformation). Associations between content and responses were examined using Pearson{\textquoteright}s chi-squared test, two-sample t-test, and linear regression. RESULTS: Posts that included written comments from the study period were analyzed. Negative emotional responses appeared in 30\% of posts and positive emotional responses were in 16\% of posts. Misinformation was more likely to appear in pre-procedure posts (5.3\% versus 1.4\%, p =\&nbsp;.03). Negative emotional responses trended towards being more common in topics related to repeat procedures (40\% vs 28\%), although this did not reach statistical significance (p\&nbsp;=\&nbsp;.06). CONCLUSIONS: Surgeons should be aware that patients frequently express negative experiences on this forum, asked for medical advice, even in the post-operative period, and that these posts generated high engagement. Misinformation may be propagated in support groups, though less commonly with regard to post-procedural questions.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2168492},
	author = {Ruran, Hana B and Petty, Carter R and Eliott, Dean and Rao, Rajesh C and Phipatanakul, Wanda and Young, Benjamin K}
}
@article {1789066,
	title = {Preloaded DMEK with endo-in technique: Standardizing and minimizing the learning curve over 5 years using 599 corneal tissues},
	journal = {Eur J Ophthalmol},
	year = {2023},
	month = {2023 Dec 15},
	pages = {11206721231217127},
	abstract = {PURPOSE: To report the outcomes of standardizing pre-loaded DMEK with endothelium-inwards and its associated learning curve. METHODS: Between 2017 and 2021, a total of 599 tissues were stripped using {\textquoteright}trephine and strip{\textquoteright} method and loaded by folding the tissue as a taco-fold with endothelium-inwards. The folded tissues were pulled inside the funnel of a 2.2 mm IOL cartridge and stored for the desired number of days in organ culture media supplemented with dextran. Donor characteristics, endothelial cell loss (ECL) and mortality assessed by trypan blue positivity before and after stripping, and eventful cases during stripping/loading were recorded. RESULTS: The tissues found unsuitable for transplant after stripping (6.7\%) were significantly higher compared with loading (0.67\%). Central or peripheral tears, fragility of the tissues, and insufficient endothelial cell density mainly attributed towards the discard rate. Mean ECL from pre-stripping to post-stripping was 0.27\% with endothelial cell mortality of 0.64\% at the end of stripping. Cumulative endothelial mortality fold change (pre-strip to post-strip) was high in the first two years of operation (18.9\%), which reduced to 5.1\% in the following three years with significant difference (p = 0.0352). Average tissue wastage (3 operators) from first 1-150 tissues was 3\%, which significantly reduced to 0.9\% after achieving the learning curve (151-250) (p = 0.0492). CONCLUSION: DMEK graft preparation requires a learning curve. However, an operator with DMEK stripping skills can easily adapt to pre-loading a DMEK graft in endothelium-inwards fashion with minimal learning curve.},
	issn = {1724-6016},
	doi = {10.1177/11206721231217127},
	author = {Ruzza, Alessandro and Grassetto, Andrea and Favaro, Elisa and Baruzzo, Mattia and Romano, Vito and Ponzin, Diego and Ferrari, Stefano and Parekh, Mohit}
}
@article {1367190,
	title = {Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy?},
	journal = {Prog Retin Eye Res},
	volume = {40},
	year = {2014},
	pages = {16-34},
	author = {Pennock S and Haddock LJ and Eliott D and Mukai S and Kazlauskas A}
}
@article {1642390,
	title = {Screening first-degree relatives of glaucoma patients reveals barriers to participation},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {5},
	year = {2022},
	pages = {655-9},
	author = {Shroff S and Gu SZ and Vardhan S A and Mani I and Aziz K and P, Namperumalsamy and Datta D and Friedman DS}
}
@inbook {1367075,
	title = {Transcriptional and Post Transcriptional Control of Enterococcal Gene Regulation},
	booktitle = {Enterococci: From Commensals to Leading Causes of Drug Resistant Infection [Internet] Boston: Massachusetts Eye and Ear Infirmary; 2014-},
	year = {2014},
	abstract = {Available at http://www.ncbi.nlm.nih.gov/books/NBK190422/},
	author = {DebRoy S and Gao P and Garsin DA and Harvey BR and Kos V and Nes IF and Solheim M}
}
@article {1059816,
	title = {Mapping Transposon Insertions in Bacterial Genomes by Arbitrarily Primed PCR},
	journal = {Curr Protoc Mol Biol},
	volume = {118},
	year = {2017},
	month = {2017 Apr 03},
	pages = {15.15.1-15.15.15},
	abstract = {Transposons can be used to easily generate and label the location of mutations throughout bacterial and other genomes. Transposon insertion mutants may be screened for a phenotype as individual isolates, or by selection applied to a pool of thousands of mutants. Identifying the location of a transposon insertion is critical for connecting phenotype to the genetic lesion. In this unit, we present an easy and detailed approach for mapping transposon insertion sites using arbitrarily-primed PCR (AP-PCR). Two rounds of PCR are used to (1) amplify DNA spanning the transposon insertion junction, and (2) increase the specific yield of transposon insertion junction fragments for sequence analysis. The resulting sequence is mapped to a bacterial genome to identify the site of transposon insertion. In this protocol, AP-PCR as it is routinely used to map sites of transposon insertion within Staphylococcus aureus, is used to illustrate the principle. Guidelines are provided for adapting this protocol for mapping insertions in other bacterial genomes. Mapping transposon insertions using this method is typically achieved in 2 to 3 days if starting from a culture of the transposon insertion mutant. {\textcopyright} 2017 by John Wiley \&amp; Sons, Inc.},
	issn = {1934-3647},
	doi = {10.1002/cpmb.38},
	author = {Saavedra, Jos{\'e} T and Schwartzman, Julia A and Gilmore, Michael S}
}
@article {1347444,
	title = {Resolvin D1 treatment on goblet cell mucin and immune responses in the chronic allergic eye disease (AED) model},
	journal = {Mucosal Immunol},
	volume = {12},
	number = {1},
	year = {2019},
	month = {2019 01},
	pages = {145-153},
	abstract = {Severe, chronic eye allergy is an understudied, vision-threatening condition. Treatments remain limited. We used a mouse model of severe allergic eye disease (AED) to determine whether topical application of the pro-resolution mediator Resolvin D1 (RvD1) terminates the response. AED was induced by injection of ovalbumin (OVA) followed by topical challenge of OVA daily. RvD1 was applied topically prior to OVA. Clinical symptoms were scored. Eye washes were assayed for MUC5AC. After 7 days, eyes were removed and the number of goblet cells, T helper cell responses and presence of immune cells in draining lymph nodes and conjunctiva determined. Topical RvD1 treatment significantly reduced symptoms of AED. RvD1 did not alter the systemic type 2 immune response in the lymph nodes. AED increased the total amount of goblet cell mucin secretion, but not the number of goblet cells. RvD1 prevented this increase, but did not alter goblet cell number. Absolute numbers of CD4 + T cells, total CD11b + myeloid cells, eosinophils, neutrophils, and monocytes, but not macrophages increased in AED versus RvD1-treated mice. We conclude that topical application of RvD1 reduced the ocular allergic response by local actions in conjunctival immune response and a decrease in goblet cell mucin secretion.},
	issn = {1935-3456},
	doi = {10.1038/s41385-018-0089-1},
	author = {Saban, Daniel R and Hodges, Robin R and Mathew, Rose and Reyes, Nancy J and Yu, Chen and Kaye, Rebecca and Swift, William and Botten, Nora and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1360121,
	title = {Residual vision activation and the brain-eye-vascular triad: Dysregulation, plasticity and restoration in low vision and blindness - a review},
	journal = {Restor Neurol Neurosci},
	year = {2018},
	month = {2018 Nov 08},
	abstract = {Vision loss due to ocular diseases such as glaucoma, optic neuropathy, macular degeneration, or diabetic retinopathy, are generally considered an exclusive affair of the retina and/or optic nerve. However, the brain, through multiple indirect influences, has also a major impact on functional visual impairment. Such indirect influences include intracerebral pressure, eye movements, top-down modulation (attention, cognition), and emotionally triggered stress hormone release affecting blood vessel dysregulation. Therefore, vision loss should be viewed as the result of multiple interactions within a "brain-eye-vascular triad", and several eye diseases may also be considered as brain diseases in disguise. While the brain is part of the problem, it can also be part of the solution. Neuronal networks of the brain can "amplify" residual vision through neuroplasticity changes of local and global functional connectivity by activating, modulating and strengthening residual visual signals. The activation of residual vision can be achieved by different means such as vision restoration training, non-invasive brain stimulation, or blood flow enhancing medications. Modulating brain functional networks and improving vascular regulation may offer new opportunities to recover or restore low vision by increasing visual field size, visual acuity and overall functional vision. Hence, neuroscience offers new insights to better understand vision loss, and modulating brain and vascular function is a promising source for new opportunities to activate residual vision to achieve restoration and recovery to improve quality of live in patients suffering from vision loss.},
	issn = {1878-3627},
	doi = {10.3233/RNN-180880},
	author = {Sabel, Bernhard A and Flammer, Josef and Merabet, Lotfi B}
}
@article {1302180,
	title = {Diagnosing Stroke in Acute Dizziness and Vertigo: Pitfalls and Pearls},
	journal = {Stroke},
	volume = {49},
	number = {3},
	year = {2018},
	month = {2018 Mar},
	pages = {788-795},
	issn = {1524-4628},
	doi = {10.1161/STROKEAHA.117.016979},
	author = {Saber Tehrani, Ali S and Kattah, Jorge C and Kerber, Kevin A and Gold, Daniel R and Zee, David S and Urrutia, Victor C and Newman-Toker, David E}
}
@article {1466913,
	title = {Management of Meibomian Gland Dysfunction: A Review},
	journal = {Surv Ophthalmol},
	year = {2019},
	month = {2019 Sep 05},
	abstract = {Meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye disease and is one of the most common conditions encountered by eye care providers. MGD is characterized by obstruction of the meibomian gland terminal ducts and/or changes in their glandular secretion, resulting in changes in tear film stability, inflammation, and symptoms of irritation. There is no gold standard treatment for MGD, but rather a diversity of options. Conservative measures include warm compresses and lid hygiene, but there is growing interest and need for medical treatments and procedures. Potential medical treatments include antibiotics, non-steroidal and steroidal anti-inflammatory agents, essential fatty acid supplementation, hormone therapy, and control of Demodex infestation. Procedures include intraductal meibomian gland probing, the use of electronic heating devices, intense pulsed light therapy, and intranasal neurostimulation. We provide an update on MGD treatments based on recent studies.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2019.08.007},
	author = {Sabeti, Saama and Kheirkhah, Ahmad and Yin, Jia and Dana, Reza}
}
@article {439641,
	title = {Vision-Related Quality of Life in Patients with Ocular Graft-versus-Host Disease.},
	journal = {Ophthalmology},
	volume = {122},
	number = {8},
	year = {2015},
	month = {2015 Aug},
	pages = {1669-74},
	abstract = {PURPOSE: To assess the vision-related quality of life (QOL) in a cohort of patients with ocular graft-versus-host disease (GVHD). DESIGN: Prospective study. PARTICIPANTS: Eighty-four patients diagnosed with chronic ocular GVHD. METHODS: We assessed the vision-related QOL with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires. MAIN OUTCOME MEASURES: We assessed vision-related QOL with the NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD with those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and the dry eye symptoms measured by the OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time, and Schirmer test. RESULTS: The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5{\textpm}17. Compared with healthy subjects, patients with ocular GVHD reported reduced scores on all NEI-VFQ-25 subscales (each P \&lt; 0.001) with the exception of color vision (P\&nbsp;= 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R\&nbsp;=\&nbsp;-0.81, P \&lt; 0.001), SANDE (R\&nbsp;=\&nbsp;-0.56, P \&lt; 0.001), CFS (R\&nbsp;=\&nbsp;-0.36, P\&nbsp;= 0.001), and BCVA (R\&nbsp;=\&nbsp;-0.30, P\&nbsp;= 0.004). CONCLUSIONS: Patients with ocular GVHD experience measurable impairment of vision-related QOL. This study highlights the impact of ocular GVHD on the vision-related QOL, and thus the importance of comprehensive diagnosis and treatment of this condition.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.04.011},
	author = {Saboo, Ujwala S and Amparo, Francisco and Abud, Tulio B and Schaumberg, Debra A and Dana, Reza}
}
@article {369046,
	title = {Outcomes of phacoemulsification in patients with chronic ocular graft-versus-host disease.},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {253},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {901-7},
	abstract = {PURPOSE: The purpose of this study was to evaluate the outcomes of phacoemulsification in patients with ocular graft-versus-host disease (GVHD). METHODS: The occurrence of cataracts, cataract surgery, and its outcomes were analyzed in the medical records of 229 patients (458 eyes) with ocular GVHD. Outcome measures included pre- and postoperative corrected distance visual acuity (CDVA) and the rate of postoperative complications. RESULTS: Of the 458 eyes evaluated, 58 were pseudophakic; from the 400 phakic eyes, 238 (59\&nbsp;\%) presented with cataracts and 62 (26\&nbsp;\%) underwent cataract surgery. Analysis of postoperative complications and visual outcomes at 1\&nbsp;month was performed in 51 eyes in which detailed surgical and immediate postoperative records were available. Preoperatively, the mean CDVA was 0.67 {\textpm} 0.57 LogMAR (Snellen 20/93), improving postoperatively to 0.17 {\textpm} 0.18 (Snellen 20/29) at 1\&nbsp;month (P \&lt; 0.0001), and to 0.13 {\textpm} 0.14 (Snellen 20/26) by the final follow-up visit (P \&lt; 0.0001). Postoperative complications included corneal epithelial defects (8\&nbsp;\%), filamentary keratitis (6\&nbsp;\%), worsening of corneal epitheliopathy (16\&nbsp;\%), posterior capsular opacification (18\&nbsp;\%), and cystoid macular edema (4\&nbsp;\%). A corrected distance visual acuity of 20/30 or better was achieved in 87\&nbsp;\% of the eyes; suboptimal CDVA improvement was attributable to severe ocular surface disease, pre-existing advanced glaucoma, and prior macular surgery. CONCLUSIONS: Phacoemulsification in patients with chronic ocular GVHD is a safe and efficacious procedure resulting in significant visual improvement. Overall, postoperative adverse events responded well to timely management.},
	issn = {1435-702X},
	doi = {10.1007/s00417-015-2940-3},
	author = {Saboo, Ujwala S and Amparo, Francisco and Shikari, Hasanain and Jurkunas, Ula V and Dana, Reza}
}
@article {669246,
	title = {Prevalence of ocular hypertension and glaucoma in patients with chronic ocular graft-versus-host disease.},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {254},
	number = {5},
	year = {2016},
	month = {2016 May},
	pages = {923-8},
	abstract = {PURPOSE: To evaluate the prevalence of ocular hypertension (OHT) and glaucoma in patients with chronic ocular graft-versus-host disease (GVHD). METHODS: We performed a retrospective chart review of 218 patients diagnosed with chronic ocular GVHD. Ocular hypertension was defined as intraocular pressure (IOP) >= 24\&nbsp;mmHg in either eye without any glaucomatous optic disc changes. Glaucoma suspect was defined as optic disc changes with a cup-to-disc ratio >= 0.7 in either eye or asymmetry of >= 0.3 between the two eyes. Glaucoma was defined by glaucomatous optic disc changes plus glaucomatous visual field defects in two consecutive reliable visual field tests. The number of cases of ocular hypertension, glaucoma, and glaucoma suspects was evaluated. RESULTS: Thirty-three patients (15\&nbsp;\%) were diagnosed with OHT, eight patients (3.6\&nbsp;\%) with suspicion of glaucoma, and one patient (0.4\&nbsp;\%) with glaucoma. OHT occurred within 6\&nbsp;months of developing ocular GVHD in 60\&nbsp;\% of the cases and within the first year in 76\&nbsp;\%. High IOP normalized in 67\&nbsp;\% of patients when the dosage of topical or systemic corticosteroids was lowered, and 27\&nbsp;\% of patients required anti-glaucoma therapy. CONCLUSIONS: Ocular hypertension is a common complication in patients with ocular GVHD, with a prevalence of 15\&nbsp;\%. The rise in intraocular pressure is often transient and resolves with management of corticosteroids in most cases. However, clinicians should be aware that nearly one-third of the patients with OHT might require anti-glaucoma treatment. The prevalences of glaucoma and suspicion of glaucoma were not higher than in the general population.},
	issn = {1435-702X},
	doi = {10.1007/s00417-016-3312-3},
	author = {Saboo, Ujwala S and Amparo, Francisco and Shikari, Hasanain and Dana, Reza}
}
@article {931151,
	title = {Clinical and Ultrastructural Studies of Epiretinal Pigmentary Deposits after Retinectomy with Silicone Oil.},
	journal = {Ophthalmology},
	volume = {123},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {2595-2602},
	abstract = {PURPOSE: Large relaxing retinectomies have become increasingly used in the repair of retinal detachment related to proliferative vitreoretinopathy (PVR). Retinectomies expose the retinal pigment epithelium (RPE) to the vitreous cavity; the direct effects of silicone oil on the RPE are only beginning to be understood. DESIGN: Retrospective case series. PARTICIPANTS: Twelve patients noted to develop pigmented epiretinal deposits at regularly scheduled follow-up visits after repair of complex retinal detachments using silicone oil tamponade and retinectomy. METHODS: Epiretinal pigment deposits were characterized clinically by wide-field color photography, fundus autofluorescence imaging, and spectral-domain optical coherence tomography (SD OCT). At the time of silicone oil removal, the pigmented membranes were preserved in fixative and analyzed by light microscopy/immunostaining or electron microscopy for histologic characterization. MAIN OUTCOME MEASURES: Not applicable. RESULTS: We describe the development of diffuse preretinal pigmentary deposits in 12 eyes after surgery for complicated PVR detachments using retinectomies with oil, with an average onset of 3.2 months postoperatively. These pigment clumps produced a striking leopard-spot pattern on fundus autofluorescence imaging. Histopathologic and ultrastructural analysis of these epiretinal proliferations peeled at the time of silicone oil removal revealed RPE cells with intracellular silicone oil droplets, singly dispersed membrane-bound melanin granules, glial tissue (1 case), and a fibrous stroma. CONCLUSIONS: Although in\&nbsp;vitro studies have suggested that RPE cells can phagocytose emulsified oil droplets, this report represents the first in\&nbsp;vivo documentation by electron microscopy of this phenomenon in patients. These findings underscore that direct contact with silicone oil may affect the behavior of the RPE, which may be clinically relevant in patients who have undergone large relaxing retinectomies with silicone oil tamponade for PVR-related retinal detachments.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.08.049},
	author = {Sachdeva, Mira M and Jakobiec, Frederick A and Stagner, Anna M and Papakostas, Athanasios and Eliott, Dean}
}
@article {1364535,
	title = {Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: host-microbe interactions in intraocular infection},
	journal = {Prog Retin Eye Res},
	volume = {31},
	number = {4},
	year = {2012},
	month = {2012 Jul},
	pages = {316-31},
	abstract = {Bacterial endophthalmitis is a sight threatening infection of the interior structures of the eye. Incidence in the US has increased in recent years, which appears to be related to procedures being performed on an aging population. The advent of outpatient intravitreal therapy for management of age-related macular degeneration raises yet additional risks. Compounding the problem is the continuing progression of antibiotic resistance. Visual prognosis for endophthalmitis depends on the virulence of the causative organism, the severity of intraocular inflammation, and the timeliness of effective therapy. We review the current understanding of the pathogenesis of bacterial endophthalmitis, highlighting opportunities for the development of improved therapeutics and preventive strategies.},
	keywords = {Anti-Bacterial Agents, Cataract Extraction, Endophthalmitis, Eye Infections, Bacterial, Humans, Immunosuppressive Agents, Intravitreal Injections, Steroids},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2012.03.004},
	author = {Sadaka, Ama and Durand, Marlene L and Gilmore, Michael S}
}
@article {303836,
	title = {In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection},
	journal = {PLoS One},
	volume = {9},
	number = {10},
	year = {2014},
	month = {2014},
	pages = {e110872},
	abstract = {PURPOSE: To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model. METHODS: For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored. RESULTS: Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated >=10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection. CONCLUSION: Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity.},
	keywords = {Amino Acids, Branched-Chain, Animals, Aqueous Humor, Bacterial Proteins, Cattle, Electroretinography, Endophthalmitis, Eye Infections, Female, Gene Deletion, Gene Expression Regulation, Bacterial, Inflammation, Mice, Mice, Inbred C57BL, Mutation, Open Reading Frames, Repressor Proteins, Staphylococcal Infections, Staphylococcus aureus, Transcriptome, Virulence, Vitreous Body},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0110872},
	author = {Sadaka, Ama and Palmer, Kelli and Suzuki, Takashi and Gilmore, Michael S}
}
@article {1364536,
	title = {Proliferative vitreoretinopathy: current and emerging treatments},
	journal = {Clin Ophthalmol},
	volume = {6},
	year = {2012},
	month = {2012},
	pages = {1325-33},
	abstract = {Proliferative vitreoretinopathy is a disease process that follows the proliferation of ectopic cell sheets in the vitreous and/or periretinal area, causing periretinal membrane formation and traction, in patients with rhegmatogenous retinal detachments. Currently, vitreous surgery is the standard treatment; however, the results aren{\textquoteright}t satisfactory given the vision loss that ensues and that redetachment is relatively common. It is becoming clearer that there exists an interplay between various cytokines/growth factors, matrix proteins, and the different cell types that drive the undesirable formation of periretinal membranes. This fundamental understanding is aiding in identifying different adjunct agents that can block the cellular events intrinsic to proliferative vitreoretinopathy. In this review, we describe the current understanding on the pathogenesis and discuss how the fundamental understanding of the biochemical/molecular events is instrumental in developing the novel treatment strategies that are also highlighted.},
	issn = {1177-5483},
	doi = {10.2147/OPTH.S27896},
	author = {Sadaka, Ama and Giuliari, Gian Paolo}
}
@article {1016121,
	title = {Staphylococcus aureus and its Bearing on Ophthalmic Disease},
	journal = {Ocul Immunol Inflamm},
	volume = {25},
	number = {1},
	year = {2017},
	month = {2017 Feb},
	pages = {111-121},
	abstract = {PURPOSE: To review antibiotic resistance associated with S. aureus endophthalmitis and the virulence of S. aureus. METHODS: Review of the current and prospective approaches for treating S. aureus endophthalmitis. RESULTS: Bacterial endophthalmitis remains to be a major threat for vision. S. aureus endophthalmitis specifically, carries a poor visual prognosis making early diagnosis and treatment crucial. Methicillin resistant Staphylococcus aureus (MRSA) endophthalmitis represents a significant number of S. aureus endophthalmitis cases. MRSA with reduced susceptibility to glycopeptide antibiotics such as vancomycin (vancomycin intermediate S. aureus, VISA) have also emerged in the ocular infections, and there has been a rise in S. aureus resistance to new and old generation fluoroquinolones that are commonly used for prophylaxis after intravitreal injections and intraocular surgeries. CONCLUSIONS: With the rise in the number of penetrating procedures in the ophthalmology practice and the parallel rise in antibiotic resistance, prophylaxis and awareness of the antimicrobial resistance profiles remain crucial and the identification of novel antimicrobials is essential.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2015.1075559},
	author = {Sadaka, Ama and Durand, Marlene L and Sisk, Robert and Gilmore, Michael S}
}
@article {1511482,
	title = {Quantitative Assessment of the Severity of Diabetic Retinopathy},
	journal = {Am J Ophthalmol},
	volume = {218},
	year = {2020},
	month = {2020 Oct},
	pages = {342-352},
	abstract = {PURPOSE: To determine whether a quantitative approach to assessment of the severity of diabetic retinopathy (DR) lesions on ultrawide field (UWF) images can provide new parameters to predict progression to proliferative diabetic retinopathy (PDR). METHODS: One hundred forty six eyes from 73 participants with DR and 4 years of follow-up data were included in this post hoc analysis, which was based on a cohort of 100 diabetic patients enrolled in a previously published prospective, comparative study of UWF imaging at the Joslin Diabetes Center. Diabetic Retinopathy Severity Score level was determined at baseline and 4-year follow-up visits using mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs. All individual DR lesions (hemorrhage [H], microaneurysm [ma], cotton wool spot [CWS], intraretinal microvascular abnormality [IRMA]) were manually segmented on stereographic projected UWF. For each lesion type, the frequency/number, surface area, and distances from the optic nerve head (ONH) were computed. These quantitative parameters were compared between eyes that progressed to PDR in 4 years and eyes that did not progress. Univariable and multivariable logistic regression analyses were performed to identify parameters that were associated with an increased risk for progression to PDR. RESULTS: A total of 146 eyes of 73 subjects were included in the final analysis. The mean age of the study cohort was 53.1 years, and 42 (56.8\%) subjects were female. The number and surface area of H/ma{\textquoteright}s and CWSs were significantly (P <= .05) higher in eyes that progressed to PDR compared with eyes that did not progress by 4 years. Similarly, H/ma{\textquoteright}s and CWSs were located further away from the ONH (ie, more peripheral) in eyes that progressed (P \&lt; .05). DR lesion parameters that conferred a statistically significant increased risk for proliferative diabetic retinopathy in the multivariate model included hemorrhage area (odds ratio [OR], 2.63; 95\% confidence interval [CI], 1.25-5.53), and greater distance of hemorrhages from the ONH (OR, 1.24; 95\% CI, 0.97-1.59). CONCLUSIONS: Quantitative analysis of DR lesions on UWF images identifies new risk parameters for progression to PDR including the surface area of hemorrhages and the distance of hemorrhages from the ONH. Although these risk factors will need to be confirmed in larger, prospective studies, they highlight the potential for quantitative lesion analysis to inform the design of a more precise and complete staging system for diabetic retinopathy severity in the future. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.05.021},
	author = {Sadda, Srinivas R and Nittala, Muneeswar G and Taweebanjongsin, Wongsiri and Verma, Aditya and Velaga, Swetha B and Alagorie, Ahmed Roshdy and Sears, Connie M and Silva, Paolo S and Aiello, Lloyd P}
}
@article {1603873,
	title = {Data mining and network analysis reveals C-X-C chemokine receptor type 5 is involved in the pathophysiology of age-related macular degeneration},
	journal = {J Biomol Struct Dyn},
	year = {2021},
	month = {2021 Jul 09},
	pages = {1-10},
	abstract = {Our previous studies found that the C-X-C motif chemokine receptor 5 (CXCR5) loss leads to retinal pigment epithelium (RPE) dysfunction and AMD pathogenesis. The current study aimed to characterize the G protein-coupled receptor (GPCR) structure of CXCR5 and analyze its interactions with AMD-related risk genes. The sequence alignments, homology model of CXCR5 and structural assessment analysis were performed. Data and text mining were then performed to identify AMD-related risk genes and their interaction with CXCR5 using statistical and mathematical algorithms. Sequence alignment and phylogenetic tree analysis revealed that human CXCR5 was highly similar (85.4839\%) to the rabbit. The least similarity (33.871\%) was found to be in zebrafish compared to the other species. The CXCR5 model structural assessment and secondary structure analysis exhibited an excellent model. Network analysis revealed that IL10, TNF, ICAM1, CXCL1, CXCL8, APP, TLR4, SELL, C3, IL17A and CCR2 were the most connected genes CXCR5. These findings suggest that CXCR5 signaling may regulate the biological function of RPE and modulate AMD pathophysiology via GPCR signaling and interacting with identified AMD risk genes. In summary, the data presented here provide novel and crucial insights into the molecular mechanisms of CXCR5 involvement in AMD.Communicated by Ramaswamy H. Sarma.},
	issn = {1538-0254},
	doi = {10.1080/07391102.2021.1949391},
	author = {Saddala, Madhu Sudhana and Lennikov, Anton and Mukwaya, Anthony and Yang, Xu and Tang, Shibo and Huang, Hu}
}
@article {1806661,
	title = {Long-Term Outcomes of 6-Week Treatment of Lotilaner Ophthalmic Solution, 0.25\%, for Demodex Blepharitis: A Noninterventional Extension Study},
	journal = {Cornea},
	year = {2024},
	month = {2024 Feb 09},
	abstract = {PURPOSE: The aim of this study was to evaluate the long-term outcomes of lotilaner ophthalmic solution, 0.25\%, in the treatment of Demodex blepharitis. METHODS: This observational, extension study included patients with Demodex blepharitis (N = 239) who completed the Saturn-1 study and presented for the day 180 visit. All participants were assessed at days 180 and 365 after the initiation of 6-week treatment with the study drug or its vehicle. RESULTS: The proportion of patients with 0 to 2 collarettes (grade 0) was significantly higher in the study group (N = 128 patients) than in the control group (N = 111 patients) (39.8\% vs. 2.7\% at day 180 and 23.5\% vs. 2.9\% at day 365; P \&lt; 0.0001). Similarly, the proportion of patients with <=10 collarettes (collarette grade 0-1) in the study group was significantly higher than in the control group (70.3\% vs. 18.0\% at day 180 and 62.6\% vs. 21.9\% at day 365; P \&lt; 0.0001). In the study group, erythema continued to improve even after completion of the 6-week lotilaner treatment. No serious ocular adverse events were observed in the study group, and there was 1 treatment-related ocular adverse event in the study group, which was considered mild. CONCLUSIONS: After 6-week treatment with lotilaner ophthalmic solution, 0.25\%, for Demodex blepharitis, no long-term concerns were observed during 1 year of follow-up. A high proportion of patients with 0 to 2 collarettes (grade 0) or <=10 collarettes (collarette grade of 0 or 1) was observed throughout 1 year of follow-up, indicating that the efficacy of lotilaner ophthalmic solution, 0.25\%, against Demodex blepharitis may last well after completion of therapy.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003484},
	author = {Sadri, Ehsan and Paauw, James D and Ciolino, Joseph B and Nijm, Lisa and Simmons, Blake and Meyer, John and Gaddie, Ian Benjamin and Berdy, Gregg J and Holdbrook, Mark and Baba, Stephanie N and Jalalat, Parisa and Yeu, Elizabeth}
}
@article {882981,
	title = {Ocular manifestations of Stevens-Johnson syndrome and their management.},
	journal = {Curr Opin Ophthalmol},
	year = {2016},
	month = {2016 Aug 31},
	abstract = {PURPOSE OF REVIEW: Recent advances and outcomes data in the management of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) demonstrate the need for a universal standard of care for patients admitted with the disease. RECENT FINDINGS: Amniotic membrane transplantation, aggressive topical corticosteroids, and lubrication in the acute stage are necessary to prevent or mitigate long-term ocular sequelae. If chronic ocular disease does occur, several interventions can be employed to prevent progressive vision loss and discomfort. The earliest interventions are the ones most likely to prevent chronic complications. SUMMARY: The literature overwhelmingly describes acute intervention for ocular involvement in SJS/TEN as improving long-term outcomes. All patients admitted for SJS/TEN or suspicion of SJS/TEN should be evaluated and then closely followed by ophthalmologists. As the disease progresses, the interventions needed for visual rehabilitation become more invasive and higher risk.},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000312},
	author = {Saeed, Hajirah N and Chodosh, James}
}
@article {1474183,
	title = {Highlights from the 2nd Biennial Stevens Johnson syndrome symposium 2019: SJS/TEN from Science to Translation},
	journal = {Ocul Surf},
	volume = {18},
	number = {3},
	year = {2020},
	month = {2020 07},
	pages = {483-486},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.11.012},
	author = {Saeed, Hajirah N and Bouchard, Charles and Shieh, Christine and Phillips, Elizabeth and Chodosh, James}
}
@article {416901,
	title = {Complications of Stevens-Johnson syndrome beyond the eye and skin.},
	journal = {Burns},
	volume = {42},
	number = {1},
	year = {2016},
	month = {2016 Feb},
	pages = {20-7},
	abstract = {INTRODUCTION: Ocular and cutaneous disease are common chronic sequelae of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and have been well described in the literature. Long-term complications affecting other organ systems have not been so well described. The purpose of this review article is to highlight non-ocular and non-cutaneous chronic complications of SJS/TEN. METHODS: The PubMed database was searched for the keywords "Stevens-Johnson syndrome" and "toxic epidermal necrolysis" through September 1, 2014. Relevant articles were then reviewed in full. RESULTS: 138 articles in the English language were found that described chronic sequelae of SJS/TEN. Our search revealed six affected organ systems other than the eyes and integument, with chronic sequelae from SJS/TEN: respiratory, gastrointestinal/hepatic, oral, otorhinolaryngologic, gynecologic/genitourinary, and renal. Complications involving these organs systems appeared likely to reduce the quality of life for SJS/TEN survivors. DISCUSSION: SJS/TEN is a multi-organ disease requiring multidisciplinary care from a variety of specialists. Affected patients have complex hospital stays, and their quality of life may be severely impacted by multiple long-term complications. We believe that preventative care in the acute setting might limit the development and progression of many of the sequelae described above.},
	issn = {1879-1409},
	doi = {10.1016/j.burns.2015.03.012},
	author = {Saeed, Hajirah and Mantagos, Iason S and Chodosh, James}
}
@article {836956,
	title = {Stevens-Johnson Syndrome and Corneal Ectasia: Management and a Case for Association.},
	journal = {Am J Ophthalmol},
	volume = {169},
	year = {2016},
	month = {2016 Sep},
	pages = {276-81},
	abstract = {PURPOSE: To report the occurrence of corneal ectasia (ECT) in patients with history of Stevens-Johnson syndrome (SJS), and to make the case for an association between these 2 diagnoses. We also report the impact of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment on visual acuity (VA) in these patients. DESIGN: Retrospective cohort study. METHODS: A manufacturing database of PROSE patients from 2002 to 2014 at Boston Foundation for Sight (BFS), a single-center clinical practice, was reviewed to identify patients with diagnoses of both SJS and ECT. RESULTS: Nine patients were identified with diagnoses of both SJS and ECT. In each case, review of the medical record revealed that diagnosis of SJS preceded that of ECT. The prevalence of ECT in this population exceeded that in the general population (P \&lt; .0001). Videokeratography was available for 13 eyes in 7 patients; using Krumeich{\textquoteright}s classification of keratoconus, 3 eyes were found to be at stage 1, 3 at stage 2, 1 at stage 3, and 6 at stage 4. Sixteen of 18 eyes underwent PROSE treatment. Of these 16 eyes, initial median VA was 20/200 (range, count fingers to 20/20; logMAR 1.0). Median VA after PROSE customization was 20/30 (range, 20/60-20/15; logMAR 0.1761, P \&lt; .0025). CONCLUSIONS: ECT occurs at a higher-than-expected rate in patients with a history of SJS. PROSE treatment improves VA in these patients. The basis of the association between SJS and ECT is considered, as well as the role of plausible contributory factors such as corneal microtrauma and matrix metalloproteinases.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.06.039},
	author = {Saeed, Hajirah N and Kohanim, Sahar and Le, Hong-Gam and Chodosh, James and Jacobs, Deborah S}
}
@article {1424816,
	title = {Agreement and Predictors of Discordance of 6 Visual Field Progression Algorithms},
	journal = {Ophthalmology},
	volume = {126},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {822-828},
	abstract = {PURPOSE: To determine the agreement of 6 established visual field (VF) progression algorithms in a large dataset of VFs from multiple institutions and to determine predictors of discordance among these algorithms. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Visual fields from 5 major eye care institutions in the United States were analyzed, including a subset of eyes with at least 5 Swedish interactive threshold algorithm standard 24-2 VFs that met our reliability criteria. Of a total of 831 240 VFs, a subset of 90 713 VFs from 13 156 eyes of 8499 patients met the inclusion criteria. METHODS: Six commonly used VF progression algorithms (mean deviation [MD] slope, VF index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort, and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen{\textquoteright}s κ coefficient. Bivariate and multivariate analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES: Agreement and discordance between algorithms. RESULTS: Individual algorithms showed poor to moderate agreement with each other when compared directly (κ range, 0.12-0.52). Based on at least 4 algorithms, 11.7\% of eyes progressed. Major predictors of discordance or lack of agreement among algorithms were more depressed initial MD (P \&lt; 0.01) and older age at first available VF (P \&lt; 0.01). A greater number of VFs (P \&lt; 0.01), more years of follow-up (P \&lt; 0.01), and eye care institution (P\&nbsp;=\&nbsp;0.03) also were associated with discordance. CONCLUSIONS: This extremely large comparative series demonstrated that existing algorithms have limited agreement and that agreement varies with clinical parameters, including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying big-data results to individual practices.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.01.029},
	author = {Saeedi, Osamah J and Tobias Elze and D{\textquoteright}Acunto, Loris and Swamy, Ramya and Hegde, Vikram and Gupta, Surabhi and Venjara, Amin and Tsai, Joby and Myers, Jonathan S and Wellik, Sarah R and De Moraes, Carlos Gustavo and Pasquale, Louis R and Shen, Lucy Q and Boland, Michael V}
}
@article {1470991,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {126},
	number = {10},
	year = {2019},
	month = {2019 Oct},
	pages = {e78-e79},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.04.036},
	author = {Saeedi, Osamah J and Tobias Elze and D{\textquoteright}Acunto, Loris and Swamy, Ramya and Hegde, Vikram and Gupta, Surabhi and Venjara, Amin and Tsai, Joby and Myers, Jonathan S and Wellik, Sarah R and De Moraes, Carlos Gustavo and Pasquale, Louis and Shen, Lucy Q and Boland, Michael V}
}
@article {1598047,
	title = {Development and Comparison of Machine Learning Algorithms to Determine Visual Field Progression},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {7},
	year = {2021},
	month = {2021 06 01},
	pages = {27},
	abstract = {Purpose: To develop and test machine learning classifiers (MLCs) for determining visual field progression. Methods: In total, 90,713 visual fields from 13,156 eyes were included. Six different progression algorithms (linear regression of mean deviation, linear regression of the visual field index, Advanced Glaucoma Intervention Study algorithm, Collaborative Initial Glaucoma Treatment Study algorithm, pointwise linear regression [PLR], and permutation of PLR) were applied to classify each eye as progressing or stable. Six MLCs were applied (logistic regression, random forest, extreme gradient boosting, support vector classifier, convolutional neural network, fully connected neural network) using a training and testing set. For MLC input, visual fields for a given eye were divided into the first and second half and each location averaged over time within each half. Each algorithm was tested for accuracy, sensitivity, positive predictive value, and class bias with a subset of visual fields labeled by a panel of three experts from 161 eyes. Results: MLCs had similar performance metrics as some of the conventional algorithms and ranged from 87\% to 91\% accurate with sensitivity ranging from 0.83 to 0.88 and specificity from 0.92 to 0.96. All conventional algorithms showed significant class bias, meaning each individual algorithm was more likely to grade uncertain cases as either progressing or stable (P <= 0.01). Conversely, all MLCs were balanced, meaning they were equally likely to grade uncertain cases as either progressing or stable (P >= 0.08). Conclusions: MLCs showed a moderate to high level of accuracy, sensitivity, and specificity and were more balanced than conventional algorithms. Translational Relevance: MLCs may help to determine visual field progression.},
	keywords = {Algorithms, Humans, machine learning, Vision Disorders, Visual Field Tests, Visual Fields},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.7.27},
	author = {Saeedi, Osamah and Boland, Michael V and D{\textquoteright}Acunto, Loris and Swamy, Ramya and Hegde, Vikram and Gupta, Surabhi and Venjara, Amin and Tsai, Joby and Myers, Jonathan S and Wellik, Sarah R and DeMoraes, Gustavo and Pasquale, Louis R and Shen, Lucy Q and Li, Yangjiani and Tobias Elze}
}
@article {1761941,
	title = {Improving Access to Eye Care in Rural Communities: PocDoc{\textquoteright}s Web-Based Visual Acuity Screening Tool},
	journal = {Telemed J E Health},
	year = {2023},
	month = {2023 Sep 14},
	abstract = {Objective: Visual acuity (VA) testing is crucial for early intervention in cases of visual impairment, especially in rural health care. This study aimed to determine the potential of a web-based VA test (PocDoc) in addressing the unique health care needs of rural areas through the comparison in its effectiveness against the conventional VA test in identifying visual impairment among an Indian rural population. Methods: Prospective comparative study conducted in December 2022 at a tertiary referral eye care center in central India. We evaluated all patients with the PocDoc VA tests using three device types, and the conventional VA test. Bland-Altman plot (BAP) compared PocDoc and conventional VA tests. Fisher{\textquoteright}s exact tests evaluated associations between categorical parameters. Kruskal-Wallis tests followed by post hoc Dunn{\textquoteright}s tests identified association between categorical parameters and numerical parameters. Results: We evaluated 428 patients (792 measurements of VA) with mean age 36.7 ({\textpm}23.3) years. PocDoc resulted in slightly worse VA scores (mean logMAR: 0.345) than conventional (mean logMAR: 0.315). Correlation coefficient between the conventional and PocDoc logMAR VA values was rho = 0.845 and rho2 = 0.7133 (p = 6.617 {\texttimes} 10-215; adjusted p = 2.205 {\texttimes} 10-214). Most data points fell within the interchangeable range of {\textpm}0.32 on BAP. Difference between the two methods increased with higher logMAR values, indicating poorer agreement for worse VA scores. Conclusions: Identifying and addressing the unique health care needs of rural populations is critical, including access to appropriate and effective VA testing methods. Validating and improving VA testing methods can ensure early intervention and improve the quality of life for individuals with visual impairment.},
	issn = {1556-3669},
	doi = {10.1089/tmj.2023.0234},
	author = {Sah, Shreya and Liu, Renee and Lai, HaoXing and Agrawal, Mahek and Jain, Priyanka and Agashe, Prathamesh and Gupta, Akshita and Madhan, Pranay and Chauhan, Ritika and Chourasiya, Kalpana and Bansod, Samiksha and Bansod, Samiksha and Singh, Gaganpreet and Sule, Ashita and Singh, Jayanti and Puah, Marilyn and Boon, Joewee and Rojas-Carabali, William and Sen, Pradnya and Lee, Bernett and Sobrin, Lucia and Sen, Alok and Agrawal, Rupesh}
}
@article {1364537,
	title = {Clinically relevant biometry},
	journal = {Curr Opin Ophthalmol},
	volume = {23},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {47-53},
	abstract = {PURPOSE OF REVIEW: Obtaining precise postoperative target refraction is of utmost importance in today{\textquoteright}s modern cataract and refractive surgery. Given the growing number of patients undergoing premium intraocular lens (IOL) implantations, patient expectation continues to rise. In order to meet heightened patient expectations, it is crucial to pay utmost attention to patient selection, accurate keratometry and biometry readings, as well as to the application of correct IOL power formula with optimized lens constants. This article reviews recent advances in the field of clinical biometry and IOL power calculations. RECENT FINDINGS: Recently developed low-coherence reflectometry optical biometry is comparable to older ultrasonic biometric and keratometric techniques. In addition, the new IOLMaster software upgrade has improved reproducibility and enhanced signal acquisition. Further, the modern lens power formulas currently determine the effective lens position and the shape of the intraocular lens power prediction curve more accurately. SUMMARY: In order to reach target refraction, precise biometric measurements are imperative. Understanding the strengths and limitations of the currently available biometry devices allows prevention of high variability and inaccuracy, ultimately determining the refractive outcomes.},
	keywords = {Biometry, Cornea, Humans, Lenses, Intraocular},
	issn = {1531-7021},
	doi = {10.1097/ICU.0b013e32834cd63e},
	author = {Sahin, Afsun and Hamrah, Pedram}
}
@article {313251,
	title = {The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis},
	journal = {Retina},
	volume = {34},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {1451-9},
	abstract = {PURPOSE: This study was designed to investigate whether the antiinflammatory and antiproliferative activity of oral and intravitreal methotrexate (MTX) suppresses intraocular inflammation in patients with presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis. METHODS: Interventional prospective study including three cases with presumed latent syphilitic uveitis treated with intravenous penicillin and oral MTX, and two cases with presumed tuberculosis-related uveitis treated with standard antituberculosis therapy and intravitreal MTX injections. Treatment efficacy of all cases was assessed by best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography. RESULTS: Four eyes of 3 patients with presumed latent syphilitic uveitis had improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema in 6 months with oral MTX therapy. No recurrence of intraocular inflammation was observed in 6 months to 18 months of follow-up period after cessation of MTX. Two eyes of two patients with presumed tuberculosis-related uveitis showed improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema after intravitreal injections of MTX. No recurrence of intraocular inflammation was observed in 6 months to 8 months of follow-up period after cessation of antituberculous therapy. CONCLUSION: For the first time in the treatment of presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis, we believe that MTX might have an adjunctive role to suppress intraocular inflammation, reduce uveitic macular edema, and prevent the recurrences of the diseases.},
	keywords = {Administration, Oral, Adult, Aged, 80 and over, Anti-Bacterial Agents, Drug Therapy, Combination, Eye Infections, Bacterial, Female, Fluorescein Angiography, Humans, Immunosuppressive Agents, Interferon-gamma Release Tests, Intravitreal Injections, Male, Methotrexate, Middle Aged, Penicillins, Prospective Studies, Syphilis Serodiagnosis, Syphilis, Latent, Tomography, Optical Coherence, Tuberculosis, Ocular, Uveitis, Visual Acuity},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000080},
	author = {Sahin, Ozlem and Ziaei, Alireza}
}
@article {1490434,
	title = {Dihydrotestosterone suppression of proinflammatory gene expression in human meibomian gland epithelial cells},
	journal = {Ocul Surf},
	volume = {18},
	number = {2},
	year = {2020},
	month = {2020 Apr},
	pages = {199-205},
	abstract = {PURPOSE: We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent proinflammatory mediator, by immortalized human meibomian gland epithelial cells (IHMGECs). We hypothesize that this hormone action reflects an androgen suppression of proinflammatory gene activity in these cells. Our goal was to test this hypothesis. For comparison, we also examined whether DHT treatment elicits the same effect in immortalized human corneal (IHC) and conjunctival (IHConj) ECs. METHODS: Differentiated cells were cultured in media containing vehicle or 10\&nbsp;nM DHT. Cells (n\&nbsp;=\&nbsp;3 wells/treatment group) were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and Geospiza software. RESULTS: Our results demonstrate that DHT significantly suppressed the expression of numerous immune-related genes in HMGECs, such as those associated with antigen processing and presentation, innate and adaptive immune responses, chemotaxis, and cytokine production. DHT also enhanced the expression of genes for defensin β1, IL-1 receptor antagonist, and the anti-inflammatory serine peptidase inhibitor, Kazal type 5. In contrast, DHT had no effect on proinflammatory gene expression in HCECs, and significantly increased 33 gene ontologies linked to the immune system in HConjECs. CONCLUSIONS: Our findings support our hypothesis that androgens suppress proinflammatory gene expression in IHMGECs. This hormone effect may contribute to the typical absence of inflammation within the human meibomian gland.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.02.006},
	author = {Sahin, Afsun and Liu, Yang and Kam, Wendy R and Rahimi Darabad, Raheleh and Sullivan, David A}
}
@article {1364538,
	title = {Acute Herpetic Keratitis: What is the Role for Ganciclovir Ophthalmic Gel?},
	journal = {Ophthalmol Eye Dis},
	volume = {4},
	year = {2012},
	month = {2012},
	pages = {23-34},
	abstract = {Herpes simplex keratitis (HSK) is a major cause of corneal blindness in the world. Following the primary infection, the virus enters into a latent phase. Recurrent infectious or immune keratitis cause structural damage to the cornea, scarring, and may lead to blindness. Several commercially available topical and oral antiviral drugs for HSK are currently available. However, toxicity and low patient compliance hamper their use in HSK. Further, oral antiviral drugs alone are not always effective in HSK. Thus, there had been a need for safe and effective topical antiviral agents against HSK. Systemic ganciclovir has been in use for the treatment of cytomegalovirus infections. Recently, topical ganciclovir has become available for use in patients with HSK. Ganciclovir 0.15\% ophthalmic gel has been shown to be both safe and effective against viruses of the herpes family. Topical ganciclovir ophthalmic gel is well tolerated and does not cause significant toxic effects on the ocular surface. Several multicenter studies have revealed the potential role of ganciclovir ophthalmic gel in the treatment and prophylaxis of epithelial HSK. In this paper, we have reviewed the pharmacology, efficacy, side effects, and the role of ganciclovir ophthalmic gel 0.15\% in the treatment of acute herpetic keratitis.},
	issn = {1179-1721},
	doi = {10.4137/OED.S7267},
	author = {Sahin, Afsun and Hamrah, Pedram}
}
@article {1417574,
	title = {The therapeutic application of mesenchymal stem cells at the ocular surface},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Jan 26},
	abstract = {The therapeutic potential of mesenchymal stem cells (MSCs) has been heralded by their multipotentiality and immunomodulatory capacity. MSCs migrate toward sites of tissue damage, where specific pro-inflammatory factors {\textquoteright}license{\textquoteright} their immunosuppressive functions. Recent studies in animal models of ocular surface disease have demonstrated the potential of MSC-derived therapies to limit inflammation and promote tissue repair. Herein, we review the immunoregulatory mechanisms of MSCs, as well as strategies to harness their regenerative function at the cornea. We examine reports of the therapeutic application of MSCs in the setting of ocular surface inflammation; including corneal injury, transplantation, ocular surface autoimmunity and allergy.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.01.006},
	author = {Sahu, Anuradha and Foulsham, William and Amouzegar, Afsaneh and Mittal, Sharad K and Chauhan, Sunil K}
}
@article {1309971,
	title = {Mast Cells Initiate the Recruitment of Neutrophils Following Ocular Surface Injury},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {5},
	year = {2018},
	month = {2018 Apr 01},
	pages = {1732-1740},
	abstract = {Purpose: The purpose of this study was to investigate the contribution of mast cells to early neutrophil recruitment during ocular inflammation. Methods: In a murine model of corneal injury, the epithelium and anterior stroma were removed using a handheld motor brush. Cromolyn sodium (2\% in PBS) eye drops were administered topically for mast cell inhibition. In vitro, bone marrow-derived mast cells were cultured alone or with corneal tissue. The frequencies of CD45+ inflammatory cells, CD11b+Ly6G+ neutrophils, and ckit+FcεR1+ mast cells in the cornea were assessed by flow cytometry. mRNA expression of CXCL2 was evaluated by real-time PCR and protein expression by ELISA. β-Hexosaminidase assays were performed to gauge mast cell activation. Results: Neutrophil infiltration of the cornea was observed within 1 hour of injury, with neutrophil frequencies increasing over subsequent hours. Concurrent expansion of mast cell frequencies at the cornea were observed, with mast cell activation (assessed by β-hexosaminidase levels) peaking at 6 hours after injury. Evaluation of CXCL2 mRNA and protein expression levels demonstrated augmented expression by injured corneal tissue relative to na{\"\i}ve corneal tissue. Mast cells were observed to constitutively express CXCL2, with significantly higher expression of CXCL2 protein compared with na{\"\i}ve corneal tissue. Culture with harvested injured corneas further amplified CXCL2 expression by mast cells. In vivo, mast cell inhibition was observed to decrease CXCL2 expression, limit early neutrophil infiltration, and reduce inflammatory cytokine expression by the cornea. Conclusions: Our data suggest that mast cell activation after corneal injury amplifies their secretion of CXCL2 and promotes the initiation of early neutrophil recruitment.},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-23398},
	author = {Sahu, Srikant K and Mittal, Sharad K and Foulsham, William and Li, Mingshun and Sangwan, Virender S and Chauhan, Sunil K}
}
@article {1661606,
	title = {Glaucoma in Patients With Endothelial Keratoplasty},
	journal = {Cornea},
	volume = {41},
	number = {12},
	year = {2022},
	month = {2022 Dec 01},
	pages = {1584-1599},
	abstract = {Endothelial keratoplasty (EK), including Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty, is now the most performed corneal transplant procedure in the United States. Intraocular pressure (IOP) elevation and glaucoma are common complications and can cause irreversible vision loss and corneal graft failure. This review will cover the incidence, risk factors, and management of glaucoma and IOP elevation after EK. Higher preoperative IOP, preoperative glaucoma, and certain indications for EK, such as bullous keratopathy, are associated with increased risk of glaucoma and glaucoma progression in patients undergoing EK. In addition, we summarize the studies assessing graft outcomes in EK patients with glaucoma or glaucoma surgery. Finally, we provide future directions to improve clinical care in EK patients with glaucoma.},
	keywords = {Corneal Diseases, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Glaucoma, Humans, Intraocular Pressure, Retrospective Studies, Tonometry, Ocular, Visual Acuity},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003122},
	author = {Saini, Chhavi and Davies, Emma C and Chodosh, James and Shen, Lucy Q}
}
@article {1761946,
	title = {Association between HSP-Specific T-Cell Counts and Retinal Nerve Fiber Layer Thickness in Patients with Primary Open-Angle Glaucoma},
	journal = {Ophthalmol Sci},
	volume = {3},
	number = {3},
	year = {2023},
	month = {2023 Sep},
	pages = {100310},
	abstract = {OBJECTIVE: Previous laboratory reports implicate heat shock protein (HSP)-specific T-cell responses in glaucoma pathogenesis; here, we aimed to provide direct clinical evidence by correlating systemic HSP-specific T-cell levels with glaucoma severity in patients with primary open-angle glaucoma (POAG). DESIGN: Cross-sectional case-control study. SUBJECTS: Thirty-two adult patients with POAG and 38 controls underwent blood draw and optic nerve imaging. METHODS: Peripheral blood monocytes (PBMC) were stimulated in culture with HSP27, α-crystallin, a member of the small HSP family, or HSP60. Both interferon-γ (IFN-γ)+ CD4+ T helper type 1 cells (Th1) and transforming growth factor-β1 (TGF-β1)+ CD4+ regulatory T cells (Treg) were quantified by flow cytometry and presented as a percentage of total PBMC counts. Relevant cytokines were measured using enzyme-linked immunosorbent assays. Retinal nerve fiber layer thickness (RNFLT) was measured with OCT. Pearson{\textquoteright}s correlation (r) was used to assess correlations. MAIN OUTCOME MEASURES: Correlations of HSP-specific T-cell counts, and serum levels of corresponding cytokine levels with RNFLT. RESULTS: Patients with POAG (visual field mean deviation, -4.7 {\textpm} 4.0 dB) and controls were similar in age, gender, and body mass index. Moreover, 46.9\% of POAG and 60.0\% of control subjects had prior cataract surgery (P\&nbsp;= 0.48). Although no significant difference in total nonstimulated CD4+ Th1 or Treg cells was detected, patients with POAG exhibited significantly higher frequencies of Th1 cells specific for HSP27, α-crystallin, or HSP60 than controls (7.3 {\textpm} 7.9\% vs. 2.6 {\textpm} 2.0\%, P\&nbsp;= 0.004; 5.8 {\textpm} 2.7\% vs. 1.8 {\textpm} 1.3\%, P \&lt; 0.001; 13.2 {\textpm} 13.3 vs. 4.3 {\textpm} 5.2, P\&nbsp;= 0.01; respectively), but similar Treg specific for the same HSPs compared with controls (P >= 0.10 for all). Concordantly, the serum levels of IFN-γ were higher in POAG than in controls (36.2 {\textpm} 12.1 pg/ml vs. 10.0 {\textpm} 4.3 pg/ml; P \&lt; 0.001), but TGF-β1 levels did not differ. Average RNFLT of both eyes negatively correlated with HSP27- and α-crystallin-specific Th1 cell counts, and IFN-γ levels in all subjects after adjusting for age (partial correlation coefficient r\&nbsp;= -0.31, P\&nbsp;= 0.03; r\&nbsp;= -0.52, p\&nbsp;= 0.002; r\&nbsp;= -0.72, P \&lt; 0.001, respectively). CONCLUSIONS: Higher levels of HSP-specific Th1 cells are associated with thinner RNFLT in patients with POAG and control subjects. The significant inverse relationship between systemic HSP-specific Th1 cell count and RNFLT supports the role of these T cells in glaucomatous neurodegeneration. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100310},
	author = {Saini, Chhavi and Jiang, Shuhong and Devlin, Julia and Pan, Li and Tang, Yizhen and Tang, Jing and Sun, Jessica A and Lorenzo, Maltish M and Wang, Qingyi and Pasquale, Louis R and Cho, Kin-Sang and Chen, Dong Feng and Shen, Lucy Q}
}
@article {1658662,
	title = {Incidence and risk factors for glaucoma development and progression after corneal transplantation},
	journal = {Eye (Lond)},
	volume = {37},
	number = {10},
	year = {2023},
	month = {2023 Jul},
	pages = {2117-2125},
	abstract = {OBJECTIVE: To assess the cumulative incidence and risk factors for glaucoma development and progression within 1-2 years following corneal transplant surgery. DESIGN: Retrospective cohort study. METHODS: Patients undergoing penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping endothelial keratoplasty (DSEK), Descemet membrane endothelial keratoplasty (DMEK), Boston keratoprosthesis type I (KPro) implantation, or endothelial keratoplasty (DSEK or DMEK) under previous PK (EK under previous PK) at one academic institution with at least 1 year of follow-up were included. Primary outcome measures were cumulative incidence of glaucoma development and progression after corneal transplant, in patients without and with preoperative glaucoma, respectively. Risk factors for glaucoma development and progression were also assessed. RESULTS: Four hundred and thirty-one eyes of 431 patients undergoing PK (113), DALK (17), DSEK (71), DMEK (168), KPro (35) and EK under previous PK (27) with a mean follow-up of 22.9 months were analyzed. The 1-year cumulative incidence for glaucoma development and progression was 28.0\% and 17.8\% in patients without and with preoperative glaucoma, respectively. In a Cox proportional hazards analysis, DSEK surgery, KPro implantation, average intraocular pressure (IOP) through follow-up and postoperative IOP spikes of >=30 mmHg were each independently associated with glaucoma development or progression (p \&lt; 0.04 for all). CONCLUSIONS: A significant proportion of patients developed glaucoma or exhibited glaucoma progression within 1 year after corneal transplantation. Patient selection for DSEK may partly explain the higher risk for glaucoma in these patients. Postoperative IOP spikes should be minimized and may indicate the need for co-management with a glaucoma specialist.},
	keywords = {Cornea, Corneal Diseases, Descemet Stripping Endothelial Keratoplasty, Follow-Up Studies, Glaucoma, Humans, Incidence, Keratoplasty, Penetrating, Prostheses and Implants, Retrospective Studies, Risk Factors},
	issn = {1476-5454},
	doi = {10.1038/s41433-022-02299-6},
	author = {Saini, Chhavi and Davies, Emma C and Ung, Lawson and Chodosh, James and Ciolino, Joseph B and Jurkunas, Ula V and Paschalis, Eleftherios I and Pineda, Roberto and Saeed, Hajirah N and Yin, Jia and Shen, Lucy Q}
}
@article {1647902,
	title = {Restoration of Vision in Severe, Cicatricial, Ocular Surface Disease With the Boston Keratoprosthesis Type II},
	journal = {Am J Ophthalmol},
	volume = {243},
	year = {2022},
	month = {2022 Nov},
	pages = {42-54},
	abstract = {PURPOSE: To assess clinical outcomes of patients with severe, cicatricial ocular surface disease (OSD) implanted with the currently marketed design of the Boston keratoprosthesis type II (BK2). DESIGN: Retrospective cohort study. METHODS: Records of consecutive patients undergoing BK2 implantation from June 2009 to March 2021 were assessed for postoperative visual acuity, postoperative complications, device replacement, and additional surgeries. RESULTS: Fifty-six eyes of 53 patients with a mean follow-up of 45.8 months (range, 0.2-134.7 months) were included. Stevens-Johnson syndrome/toxic epidermal necrolysis was the most common indication (49.1\%), followed by mucous membrane pemphigoid (39.6\%) and other OSD (11.3\%). Visual acuity improved from logMAR 2.2 {\textpm} 0.5 preoperatively to 1.5 {\textpm} 1.2 at final follow-up. Of 56 eyes, 50 saw >=20/200 at some point postoperatively. Of the eyes with a follow-up of more than 5 years, 50.0\% retained a visual acuity of >=20/200 at their final follow-up. The most common complications over the entire postoperative course (mean \~{}4 years) were de novo or worsening glaucoma (41.1\%), choroidal effusions (30.3\%), retinal detachment (25.0\%), and end-stage glaucoma (25.0\%). In a univariate analysis, patients who experienced irreversible loss of >=20/200 visual acuity were more likely to have been previously implanted with an older design of BK2, less likely to be on preoperative systemic immunosuppressive therapy, and less likely to have undergone concurrent glaucoma tube implantation, compared to patients who retained >=20/200 acuity (P \&lt; .04 for all). CONCLUSIONS: Advances in device design and postoperative care have made implantation of BK2 a viable option for corneal blindness in the setting of severe cicatricial OSD.},
	keywords = {Cornea, Corneal Diseases, Glaucoma, Humans, Prostheses and Implants, Prosthesis Implantation, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.06.022},
	author = {Saini, Chhavi and Chen, Teresa C and Young, Lucy H and Vavvas, Demetrios G and Vangel, Mark and Papaliodis, George N and Mukai, Shizuo and Turalba, Angela V and Rhee, Douglas J and Wu, David M and Eliott, Dean and Miller, John B and Song, Brian J and Shen, Lucy Q and Pasquale, Louis R and Chodosh, James}
}
@article {1351180,
	title = {Fatty acid binding protein 4 deficiency protects against oxygen-induced retinopathy in mice},
	journal = {PLoS One},
	volume = {9},
	number = {5},
	year = {2014},
	month = {2014},
	pages = {e96253},
	abstract = {Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide due to increasing survival rates of premature infants. Initial suppression, followed by increased production of the retinal vascular endothelial growth factor-A (VEGF) expression are key events that trigger the pathological neovascularization in ROP. Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone that is induced by VEGF in a subset of endothelial cells. FABP4 exhibits a pro-angiogenic function in cultured endothelial cells and in airway microvasculature, but whether it plays a role in modulation of retinal angiogenesis is not known. We hypothesized that FABP4 deficiency could ameliorate pathological retinal vascularization and investigated this hypothesis using a well-characterized mouse model of oxygen-induced retinopathy (OIR). We found that FABP4 was not expressed in retinal vessels, but was present in resident macrophages/microglial cells and endothelial cells of the hyaloid vasculature in the immature retina. While FABP4 expression was not required for normal development of retinal vessels, FABP4 expression was upregulated and localized to neovascular tufts in OIR. FABP4-/- mice demonstrated a significant decrease in neovessel formation as well as a significant improvement in physiological revascularization of the avascular retinal tissues. These alterations in retinal vasculature were accompanied by reduced endothelial cell proliferation, but no effect on apoptosis or macrophage/microglia recruitment. FABP4-/- OIR samples demonstrated decreased expression of genes involved in angiogenesis, such as Placental Growth Factor, and angiopoietin 2. Collectively, our findings suggest FABP4 as a potential target of pathologic retinal angiogenesis in proliferative retinopathies.},
	keywords = {Animals, Fatty Acid-Binding Proteins, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, Oxygen, Retinal Vessels, Retinopathy of Prematurity},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0096253},
	author = {Saint-Geniez, Magali and Ghelfi, Elisa and Liang, Xiaoliang and Yu, Chenwei and Spencer, Carrie and Abend, Stephanie and Hotamisligil, Gokhan and Cataltepe, Sule}
}
@article {1078806,
	title = {Eyeing the Fountain of Youth},
	journal = {Cell Stem Cell},
	volume = {20},
	number = {5},
	year = {2017},
	month = {2017 May 04},
	pages = {583-584},
	abstract = {Stem cell-based disease modeling is an emerging technology for the mechanistic study and therapeutic screening of complex ocular pathologies. In this issue of Cell Stem Cell, Saini et\&nbsp;al. (2017) show that iPSC-derived RPE cells from age-related macular degeneration patients express increased levels of pro-inflammatory factors that can be normalized by the anti-aging drug nicotinamide.},
	issn = {1875-9777},
	doi = {10.1016/j.stem.2017.04.007},
	author = {Saint-Geniez, Magali and Rosales, Mariana Aparecida B}
}
@article {680431,
	title = {Interleukin-22 serum levels are elevated in active scleritis.},
	journal = {Acta Ophthalmol},
	year = {2016},
	month = {2016 Mar 24},
	abstract = {PURPOSE: To evaluate serum cytokine profile from patients with active scleritis in a two-centre prospective case-control study.

METHODS: The serum of 20 active scleritis patients not treated with any local, periocular, or systemic immunomodulatory therapy (IMT) was analysed with multiplex assay to determine the levels of 11 cytokines interleukin (IL)-1β, IL-6, IL-2, IFN-γ, IL-10, IL-12p40, IL-13, IL-17A, IL-5, TNF-α, and TNF-β, and with ELISA to determine the levels of TGF-β1, IL-22, and IL-23. Twenty-five age-matched healthy volunteers were used as controls. In a subgroup of 13 patients with active disease, a second serum sample was obtained when the disease was inactive and levels of IL-22 were determined. Serum IL-22 levels from patients with active scleritis were correlated with type of scleritis (non-necrotizing and necrotizing), degree of inflammation (0-4+~:<=2+ and >2+), and associated systemic disease.

RESULTS: Serum levels of IL-22 were elevated in active scleritis patients compared to controls (6.41~{\textpm}~1.52~pg/ml versus 1.93~{\textpm}~0.39~pg/ml, p~=~0.012) and significantly decreased after scleritis remission with the use of IMT (p~=~0.005). There was no statistical association with scleritis type, degree of inflammation, or associated systemic disease. The serum levels of other cytokines were not significantly different from controls.

CONCLUSION: In our study cohort, IL-22 serum levels were significantly elevated in active scleritis patients compared to controls and decreased significantly after remission. Our results suggest that IL-22, a T helper (Th) 17- and Th22- derived cytokine, may play a critical role in the physiopathology of scleritis.},
	issn = {1755-3768},
	doi = {10.1111/aos.13005},
	author = {Sainz-de-la-Maza, Maite and Molins, Blanca and Mesquida, Marina and Lloren{\c c}, Victor and Zarranz-Ventura, Javier and Sala-Puigdollers, Anna and Matas, Jessica and Adan, Alfredo and Foster, C Stephen}
}
@article {655076,
	title = {Scleritis associated with relapsing polychondritis.},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1290-4},
	abstract = {AIMS: To evaluate ocular disease characteristics and successful therapeutic regimens in patients with scleritis associated with relapsing polychondritis (RP). To compare these features with those seen in patients with scleritis associated with other systemic immune-mediated diseases (SIMD). METHODS: Electronic health records of 13 scleritis patients associated with RP were analysed and compared with those of 113 scleritis patients associated with other SIMD seen at two tertiary referral centres. RESULTS: Scleritis in patients with RP was often bilateral (92.3\%), diffuse (76.9\%), recurrent (84.6\%), sometimes with decreased vision (46.2\%), anterior uveitis (38.5\%), peripheral keratitis (15.4\%) and ocular hypertension (30.8\%). Patients with scleritis associated with RP more often had bilateral scleritis (p=0.001), necrotising scleritis (23.1\%; p=0.02), recurrences (p=0.001) and decreased vision (three of the six with legal blindness; p=0.012), as compared with patients who had scleritis associated with other SIMD. Nine patients (69.2\%) had one or more SIMD other than RP, including systemic vasculitis (4) or other autoimmune disease (8); they antedated RP by 9 years (range 2-21 years). Successful therapy included cyclophosphamide (5), methotrexate (3), azathioprine (3), mycophenolate mofetil (2), infliximab (2) and adalimumab (1). CONCLUSIONS: Scleritis may be the first manifestation whose study leads to the diagnosis of RP. Scleritis associated with RP is more often bilateral, necrotising, recurrent and associated with decrease of vision than scleritis associated with other SIMD. About 69.2\% of patients will have an additional SIMD disorder. Scleritis associated with RP most often will require immunomodulatory therapy. Occasionally, scleritis with RP may appear while using antitumor necrosis factor α agents.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-306902},
	author = {Sainz-de-la-Maza, Maite and Molina, Nicolas and Gonzalez-Gonzalez, Luis Alonso and Doctor, Priyanka P and Tauber, Joseph and Foster, C Stephen}
}
@article {1658652,
	title = {Optic perineuritis},
	journal = {Curr Opin Ophthalmol},
	volume = {33},
	number = {6},
	year = {2022},
	month = {2022 Nov 01},
	pages = {519-524},
	abstract = {PURPOSE OF REVIEW: This review paper aims at discussing pathogenesis, etiology, clinical features, management, and prognosis of OPN. RECENT FINDINGS: Optic perineuritis (OPN) is an inflammatory process primarily involving the optic nerve sheath. Clinically, OPN usually presents with unilateral, gradual decline of visual function, eye pain, and/or pain on eye movements, disc edema and various features of optic nerve dysfunction, including visual field defects. It can mimic typical optic neuritis. In most cases of OPN, the disease is isolated with no specific etiology being identified, however, it can also occur secondary to a wide range of underlying systemic diseases. OPN is clinically diagnosed and radiologically confirmed based on the finding of circumferential perineural enhancement of the optic nerve sheath on magnetic resonance imaging (MRI). SUMMARY: Unlike optic nerve, OPN is not typically self-limited without treatment. High-dose oral corticosteroids are the mainstay of treatment in OPN. The initiation of therapy usually causes rapid and dramatic improvement in signs and symptoms. In general, OPN usually has a relatively good visual prognosis, which is influenced by delays between the onset of visual loss and the initiation of steroid therapy as well as the presence of underlying systemic diseases.},
	keywords = {Adrenal Cortex Hormones, Humans, Magnetic Resonance Imaging, Optic Neuritis, Steroids, Vision Disorders, Visual Field Tests},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000900},
	author = {Saitakis, George and Chwalisz, Bart K}
}
@article {1593835,
	title = {The neurology of IGG4-related disease},
	journal = {J Neurol Sci},
	volume = {424},
	year = {2021},
	month = {2021 05 15},
	pages = {117420},
	abstract = {PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is emerging as a fibro-inflammatory entity affecting multiple organs, including manifold neurologic manifestations. This review discusses general characteristics of IgG4-RD neurologic disease including epidemiology, histology, clinical picture and treatment approaches. RECENT FINDINGS: IgG4-RD is increasingly recognized as an important underlying pathophysiology in multiple disorders of neurologic interest, including orbital inflammation, infundibulo-hypophysitis, hypertrophic pachymeningitis, and even in rare cases CNS parenchymal disease and cranial vascular involvement. These were previously considered idiopathic and unrelated to any systemic disease but now known to share a common histopathology. New knowledge regarding the pathogenesis, clinical features and epidemiology of IgG4 is emerging, and new neurological manifestations continue to be described. Diagnostic progress includes CT-PET imaging, the use of flow cytometry for plasmablast quantification, and the use of reverse passive latex agglutination aiming to overcome the prozone phenomenon. Histopathologic confirmation of IgG4-RD remains the gold standard method of diagnosis but new diagnostic criteria for systemic and organ-specific disease are being proposed. Though glucorticoids remain the mainstay of therapy, relapses and incomplete recovery are frequent. Rituximab is a promising treatment in IgG4-RD that is severe, refractory or glucocorticoid dependent. Initiation of immunosuppression at an early stage of disease should be considered in order to avoid development of refractory fibrosis. SUMMARY: The current review emphasizes the neurologic manifestations of IgG4-RD.},
	keywords = {Autoimmune Diseases, Humans, Immunoglobulin G, Immunoglobulin G4-Related Disease, Meningitis, Neurology, Plasma Cells},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2021.117420},
	author = {Saitakis, G and Chwalisz, B K}
}
@article {1460382,
	title = {Noninvasive imaging of the tree shrew eye: Wavefront analysis and retinal imaging with correlative histology},
	journal = {Exp Eye Res},
	volume = {185},
	year = {2019},
	month = {2019 Aug},
	pages = {107683},
	abstract = {Tree shrews are small mammals with excellent vision and are closely related to primates. They have been used extensively as a model for studying refractive development, myopia, and central visual processing and are becoming an important model for vision research. Their cone dominant retina (\~{}95\% cones) provides a potential avenue to create new damage/disease models of human macular pathology and to monitor progression or treatment response. To continue the development of the tree shrew as an animal model, we provide here the first measurements of higher order aberrations along with adaptive optics scanning light ophthalmoscopy (AOSLO) images of the photoreceptor mosaic in the tree shrew retina. To compare intra-animal in vivo and ex vivo cone density measurements, the AOSLO images were matched to whole-mount immunofluorescence microscopy. Analysis of the tree shrew wavefront indicated that the optics are well-matched to the sampling of the cone mosaic and is consistent with the suggestion that juvenile tree shrews are nearly emmetropic (slightly hyperopic). Compared with in vivo measurements, consistently higher cone density was measured ex vivo, likely due to tissue shrinkage during histological processing. Tree shrews also possess massive mitochondria ("megamitochondria") in their cone inner segments, providing a natural model to assess how mitochondrial size affects in vivo retinal imagery. Intra-animal in vivo and ex vivo axial distance measurements were made in the outer retina with optical coherence tomography (OCT) and transmission electron microscopy (TEM), respectively, to determine the origin of sub-cellular cone reflectivity seen on OCT. These results demonstrate that these megamitochondria create an additional hyper-reflective outer retinal reflective band in OCT images. The ability to use noninvasive retinal imaging in tree shrews supports development of this species as a model of cone disorders.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.05.023},
	author = {Sajdak, Benjamin S and Salmon, Alexander E and Cava, Jenna A and Allen, Kenneth P and Freling, Susan and Ramamirtham, Ramkumar and Norton, Thomas T and Roorda, Austin and Carroll, Joseph}
}
@article {1460367,
	title = {RELATIONSHIP BETWEEN CHOROIDAL VASCULAR HYPERPERMEABILITY, CHORIOCAPILLARIS FLOW DENSITY, AND CHOROIDAL THICKNESS IN EYES WITH PACHYCHOROID PIGMENT EPITHELIOPATHY},
	journal = {Retina},
	volume = {40},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {657-662},
	abstract = {PURPOSE: To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy. METHODS: Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm {\texttimes} 12-mm swept-source optical coherence tomography, 12-mm {\texttimes} 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm {\texttimes} 3-mm area to explore the relationship between these 2 factors. RESULTS: Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P \&lt; 0.001). The mean choriocapillaris flow density ratio was 0.86 {\textpm} 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P \&lt; 0.001, 455 {\textpm} 122 {\textmu}m vs. 297 {\textpm} 93 {\textmu}m). CONCLUSION: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002635},
	author = {Sakurada, Yoichi and Fragiotta, Serena and Leong, Belinda C S and Parikh, Ravi and Hussnain, S Amal and Freund, K Bailey}
}
@article {1452961,
	title = {RESOLUTION OF A SUBFOVEAL CHOROIDAL CAVERN AFTER HALF-DOSE PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY},
	journal = {Retin Cases Brief Rep},
	volume = {15},
	number = {6},
	year = {2021},
	month = {2021 Nov 01},
	pages = {673-675},
	abstract = {PURPOSE: To describe resolution of a subfoveal choroidal cavern after half-dose verteporfin photodynamic therapy for persistent central serous chorioretinopathy. METHODS: Case report. RESULTS: A 43-year-old man was referred for treatment of chorioretinopathy in his left eye. On presentation, swept-source optical coherence tomography demonstrated a serous retinal detachment and a 161-μm-thick subfoveal choroidal cavern showing a characteristic tail of hypertransmission extending posteriorly. Subfoveal choroidal thickness measured 456 μm in the affected eye. Complete resolution of subretinal fluid and the subfoveal choroidal cavern were observed 3 months after half-dose verteporfin photodynamic therapy. Twelve months after treatment, subfoveal choroidal thickness had decreased further to 276 μm, and visual acuity had improved to 20/15. CONCLUSION: After half-dose verteporfin photodynamic therapy for chorioretinopathy, resolution of subretinal fluid was accompanied by resolution of a subfoveal choroidal cavern at 3 months and a 39.5\% reduction in subfoveal choroidal thickness at 1 year.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000903},
	author = {Sakurada, Yoichi and Parikh, Ravi and Freund, K Bailey}
}
@article {397861,
	title = {Regulation of Mammalian cone phototransduction by recoverin and rhodopsin kinase.},
	journal = {J Biol Chem},
	volume = {290},
	number = {14},
	year = {2015},
	month = {2015 Apr 3},
	pages = {9239-50},
	abstract = {Cone photoreceptors function under daylight conditions and are essential for color perception and vision with high temporal and spatial resolution. A remarkable feature of cones is that, unlike rods, they remain responsive in bright light. In rods, light triggers a decline in intracellular calcium, which exerts a well studied negative feedback on phototransduction that includes calcium-dependent inhibition of rhodopsin kinase (GRK1) by recoverin. Rods and cones share the same isoforms of recoverin and GRK1, and photoactivation also triggers a calcium decline in cones. However, the molecular mechanisms by which calcium exerts negative feedback on cone phototransduction through recoverin and GRK1 are not well understood. Here, we examined this question using mice expressing various levels of GRK1 or lacking recoverin. We show that although GRK1 is required for the timely inactivation of mouse cone photoresponse, gradually increasing its expression progressively delays the cone response recovery. This surprising result is in contrast with the known effect of increasing GRK1 expression in rods. Notably, the kinetics of cone responses converge and become independent of GRK1 levels for flashes activating more than \~{}1\% of cone pigment. Thus, mouse cone response recovery in bright light is independent of pigment phosphorylation and likely reflects the spontaneous decay of photoactivated visual pigment. We also find that recoverin potentiates the sensitivity of cones in dim light conditions but does not contribute to their capacity to function in bright light.},
	issn = {1083-351X},
	doi = {10.1074/jbc.M115.639591},
	author = {Sakurai, Keisuke and Chen, Jeannie and Khani, Shahrokh C and Kefalov, Vladimir J}
}
@article {1638551,
	title = {Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance},
	journal = {Genome Med},
	volume = {14},
	number = {1},
	year = {2022},
	month = {2022 Apr 05},
	pages = {37},
	abstract = {BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms. METHODS: To overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years. RESULTS: Our CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment. CONCLUSIONS: Collectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.},
	keywords = {Anti-Bacterial Agents, Carbapenems, Gene Transfer, Horizontal, Humans, Plasmids, Prospective Studies},
	issn = {1756-994X},
	doi = {10.1186/s13073-022-01040-y},
	author = {Salamzade, Rauf and Manson, Abigail L and Walker, Bruce J and Thea Brennan-Krohn and Worby, Colin J and Ma, Peijun and He, Lorrie L and Shea, Terrance P and Qu, James and Chapman, Sin{\'e}ad B and Howe, Whitney and Young, Sarah K and Wurster, Jenna I and Delaney, Mary L and Sanjat Kanjilal and Onderdonk, Andrew B and Bittencourt, Cassiana E and Gussin, Gabrielle M and Kim, Diane and Peterson, Ellena M and Ferraro, Mary Jane and Hooper, David C and Shenoy, Erica S and Cuomo, Christina A and Cosimi, Lisa A and Huang, Susan S and Kirby, James E and Pierce, Virginia M and Bhattacharyya, Roby P and Earl, Ashlee M}
}
@article {341696,
	title = {Scleral perforations during routine traction test in a patient with osteogenesis imperfecta.},
	journal = {J AAPOS},
	volume = {18},
	number = {6},
	year = {2014},
	month = {2014 Dec},
	pages = {610-2},
	abstract = {Osteogenesis imperfecta comprises a rare group of genetic disorders caused by abnormal collagen that results in increased bone fragility and other sequelae. We describe a 37-year-old woman with osteogenesis imperfecta in whom two full-thickness scleral perforations were created by adjacent teeth of 0.5 mm forceps during traction testing while undergoing routine strabismus surgery. This case reviews the ocular findings of osteogenesis imperfecta and highlights the potential risk of ocular surgical complications in these patients.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2014.07.166},
	author = {Salcone, Erin M and Hamdy, Shaden and Melki, Samir and Hunter, David G}
}
@article {1608610,
	title = {Content Validation of Clinician-Reported Items for a Severity Measure for CDKL5 Deficiency Disorder},
	journal = {J Child Neurol},
	volume = {36},
	number = {11},
	year = {2021},
	month = {2021 Oct},
	pages = {998-1006},
	abstract = {CDKL5 deficiency disorder (CDD) results in early-onset seizures and severe developmental impairments. A CDD clinical severity assessment (CCSA) was previously developed with clinician and parent-report items to capture information on a range of domains. Consistent with US Food and Drug Administration (FDA) guidelines, content validation is the first step in evaluating the psychometric properties of an outcome measure. The aim of this study was to validate the content of the clinician-reported items in the CCSA (CCSA-Clinician). Eight neurologists leading the USA CDD Center of Excellence clinics were interviewed using the "think aloud" technique to critique 26 clinician-reported items. Common themes were aggregated, and a literature search of related assessments informed item modifications. The clinicians then participated in 2 consensus meetings to review themes and finalize the items. A consensus was achieved for the content of the CCSA-Clinician. Eight of the original items were omitted, 11 items were added, and the remaining 18 items were revised. The final 29 items were classified into 2 domains: functioning and neurologic impairments. This study enabled refinement of the CCSA-Clinician and provided evidence for its content validity. This preliminary validation is essential before field testing and further validation, in order to advance the instrument toward clinical trial readiness.},
	issn = {1708-8283},
	doi = {10.1177/08830738211019576},
	author = {Saldaris, Jacinta and Weisenberg, Judith and Pestana-Knight, Elia and Marsh, Eric D and Suter, Bernhard and Rajaraman, Rajsekar and Heidary, Gena and Olson, Heather E and Devinsky, Orrin and Price, Dana and Jacoby, Peter and Leonard, Helen and Benke, Tim A and Demarest, Scott and Downs, Jenny}
}
@article {1688341,
	title = {One-field, two-field and five-field handheld retinal imaging compared with standard seven-field Early Treatment Diabetic Retinopathy Study photography for diabetic retinopathy screening},
	journal = {Br J Ophthalmol},
	year = {2023},
	month = {2023 Apr 24},
	abstract = {BACKGROUND/AIMS: To determine agreement of one-field (1F, macula-centred), two-field (2F, disc-macula) and five-field (5F, macula, disc, superior, inferior and nasal) mydriatic handheld retinal imaging protocols for the assessment of diabetic retinopathy (DR) as compared with standard seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) photography. METHODS: Prospective, comparative instrument validation study. Mydriatic retinal images were taken using three handheld retinal cameras: Aurora (AU; 50{\textdegree} field of view (FOV), 5F), Smartscope (SS; 40{\textdegree} FOV, 5F), and RetinaVue (RV; 60{\textdegree} FOV, 2F) followed by ETDRS photography. Images were evaluated at a centralised reading centre using the international DR classification. Each field protocol (1F, 2F and 5F) was graded independently by masked graders. Weighted kappa (Kw) statistics assessed agreement for DR. Sensitivity (SN) and specificity (SP) for referable diabetic retinopathy (refDR; moderate non-proliferative diabetic retinopathy (NPDR) or worse, or ungradable images) were calculated. RESULTS: Images from 225 eyes of 116 patients with diabetes were evaluated. Severity by ETDRS photography: no DR, 33.3\%; mild NPDR, 20.4\%; moderate, 14.2\%; severe, 11.6\%; proliferative, 20.4\%. Ungradable rate for DR: ETDRS, 0\%; AU: 1F 2.23\%, 2F 1.79\%, 5F 0\%; SS: 1F 7.6\%, 2F 4.0\%, 5F 3.6\%; RV: 1F 6.7\%, 2F 5.8\%. Agreement rates of DR grading between handheld retinal imaging and ETDRS photography were (Kw, SN/SP refDR) AU: 1F 0.54, 0.72/0.92; 2F 0.59, 0.74/0.92; 5F 0.75, 0.86/0.97; SS: 1F 0.51, 0.72/0.92; 2F 0.60, 0.75/0.92; 5F 0.73, 0.88/0.92; RV: 1F 0.77, 0.91/0.95; 2F 0.75, 0.87/0.95. CONCLUSION: When using handheld devices, the addition of peripheral fields decreased the ungradable rate and increased SN and SP for refDR. These data suggest the benefit of additional peripheral fields in DR screening programmes that use handheld retinal imaging.},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-321849},
	author = {Salongcay, Recivall P and Jacoba, Cris Martin P and Salva, Claude Michael G and Rageh, Abdulrahman and Aquino, Lizzie Anne C and Saunar, Aileen V and Alog, Glenn P and Ashraf, Mohamed and Peto, Tunde and Silva, Paolo S}
}
@article {1635641,
	title = {Comparison of Handheld Retinal Imaging with ETDRS 7-Standard Field Photography for Diabetic Retinopathy and Diabetic Macular Edema},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {7},
	year = {2022},
	month = {2022 Jul},
	pages = {548-556},
	abstract = {PURPOSE: To compare nonmydriatic (NM) and mydriatic (MD) handheld retinal imaging with standard ETDRS 7-field color fundus photography (ETDRS photographs) for the assessment of diabetic retinopathy (DR) and diabetic macular edema (DME). DESIGN: Prospective, comparative, instrument validation study. SUBJECTS: A total of 225 eyes from 116 patients with diabetes mellitus. METHODS: Following a standardized protocol, NM and MD images were acquired using handheld retinal cameras (NM images: Aurora, Smartscope, and RetinaVue-700; MD images: Aurora, Smartscope, RetinaVue-700, and iNview) and dilated ETDRS photographs. Grading was performed at a centralized reading center using the International Clinical Classification for DR and DME. Kappa statistics (simple [K], weighted [Kw]) assessed the level of agreement for DR and DME. Sensitivity and specificity were calculated for any DR, referable DR (refDR), and vision-threatening DR (vtDR). MAIN OUTCOME MEASURES: Agreement for DR and DME; sensitivity and specificity for any DR, refDR, and vtDR; ungradable rates. RESULTS: Severity by ETDRS photographs: no DR, 33.3\%; mild nonproliferative DR, 20.4\%; moderate DR, 14.2\%; severe DR, 11.6\%; proliferative DR, 20.4\%; no DME, 68.0\%; DME, 9.3\%; non-center involving clinically significant DME, 4.9\%; center-involving clinically significant DME, 12.4\%; and ungradable, 5.3\%. For NM handheld retinal imaging, Kw was 0.70 to 0.73 for DR and 0.76 to 0.83 for DME. For MD handheld retinal imaging, Kw was 0.68 to 0.75 for DR and 0.77 to 0.91 for DME. Thresholds for sensitivity (0.80) and specificity (0.95) were met by NM images acquired using Smartscope and MD images acquired using Aurora and RetinaVue-700 cameras for any DR and by MD images acquired using Aurora and RetinaVue-700 cameras for refDR. Thresholds for sensitivity and specificity were met by MD images acquired using Aurora and RetinaVue-700 for DME. Nonmydriatic and MD ungradable rates for DR were 15.1\% to 38.3\% and 0\% to 33.8\%, respectively. CONCLUSIONS: Following standardized protocols, NM and MD handheld retinal imaging devices have substantial agreement levels for DR and DME. With mydriasis, not all handheld retinal imaging devices meet standards for sensitivity and specificity in identifying any DR and refDR. None of the handheld devices met the established 95\% specificity for vtDR, suggesting that lower referral thresholds should be used if handheld devices must be utilized. When using handheld devices, the ungradable rate is significantly reduced with mydriasis and DME sensitivity thresholds are only achieved following dilation.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Humans, Macular Edema, Mydriasis, Photography, Prospective Studies},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.03.002},
	author = {Salongcay, Recivall P and Aquino, Lizzie Anne C and Salva, Claude Michael G and Saunar, Aileen V and Alog, Glenn P and Sun, Jennifer K and Peto, Tunde and Silva, Paolo S}
}
@article {1297783,
	title = {The Role of Teleophthalmology in the Management of Diabetic Retinopathy},
	journal = {Asia Pac J Ophthalmol (Phila)},
	year = {2018},
	month = {2018 Jan 26},
	abstract = {The emergence of diabetes as a global epidemic is accompanied by the rise in diabetes-related retinal complications. Diabetic retinopathy, if left undetected and untreated, can lead to severe visual impairment and affect an individual{\textquoteright}s productivity and quality of life. Globally, diabetic retinopathy remains one of the leading causes of visual loss in the working-age population. Teleophthalmology for diabetic retinopathy is an innovative means of retinal evaluation that allows identification of eyes at risk for visual loss, thereby preserving vision and decreasing the overall burden to the health care system. Numerous studies worldwide have found teleophthalmology to be a reliable and cost-efficient alternative to traditional clinical examinations. It has reduced barriers to access to specialized eye care in both rural and urban communities. In teleophthalmology applications for diabetic retinopathy, it is critical that standardized protocols in image acquisition and evaluation are used to ensure low image ungradable rates and maintain the quality of images taken. Innovative imaging technology such as ultrawide field imaging has the potential to provide significant benefit with integration into teleophthalmology programs. Teleophthalmology programs for diabetic retinopathy rely on a comprehensive and multidisciplinary approach with partnerships across specialties and health care professionals to attain wider acceptability and allow evidence-based eye care to reach a much broader population.},
	issn = {2162-0989},
	doi = {10.22608/APO.2017479},
	author = {Salongcay, Recivall P and Silva, Paolo S}
}
@article {1351181,
	title = {Very low risk of light-induced retinal damage during Boston keratoprosthesis surgery: a rabbit study},
	journal = {Cornea},
	volume = {33},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {184-90},
	abstract = {PURPOSE: The aim of this study was to assess the possibility of light damage to the retina by a surgical microscope during implantation of a Boston Keratoprosthesis (B-KPro) in rabbits. METHODS: The retinal irradiance from a Zeiss OPMI Lumera S7 operating microscope was measured at the working distance (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro was implanted into 1 eye of 12 rabbits with the optic covered during the procedure. The operated eyes were then continuously exposed to a fixed light intensity under the microscope for 1 hour. Fluorescein angiography was carried out on days 2 and 9 postsurgery, after which the animals were euthanized. Further, we compared the potential of these retinal exposures to well-accepted light safety guidelines applicable to humans. RESULTS: Light transmittance of B-KPro revealed a blockage of short wavelengths (\&lt;390 nm) and of long wavelengths (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography nor a histological examination showed any morphological retinal changes in our rabbits. Moreover, the retinal exposures were well below the safety limits. CONCLUSIONS: Modern surgical microscopes have filters incorporated in them that block the most damaging wavelengths of light. The B-KPro is made of 100\% poly(methyl methacrylate), which makes it in itself a blocker of short wavelengths of light. No damage could be demonstrated in the animal study, and the retinal exposures were well below the safety limits. Together, these results suggest that light exposures during B-KPro surgery present a low risk of photochemical damage to the retina.},
	keywords = {Animals, Artificial Organs, Cornea, Fluorescein Angiography, Intraoperative Period, Light, Male, Microscopy, Prosthesis Implantation, Rabbits, Radiation Injuries, Experimental, Retina, Retinal Diseases, Risk Factors},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000029},
	author = {Salvador-Culla, Borja and Behlau, Irmgard and Sayegh, Rony R and Stacy, Rebecca C and Dohlman, Claes H and Delori, Fran{\c c}ois}
}
@article {726236,
	title = {Keratoprosthesis: A Review of Recent Advances in the Field.},
	journal = {J Funct Biomater},
	volume = {7},
	number = {2},
	year = {2016},
	month = {2016},
	abstract = {Since its discovery in the years of the French Revolution, the field of keratoprostheses has evolved significantly. However, the path towards its present state has not always been an easy one. Initially discarded for its devastating complications, the introduction of new materials and the discovery of antibiotics in the last century gave new life to the field. Since then, the use of keratoprostheses for severe ocular surface disorders and corneal opacities has increased significantly, to the point that it has become a standard procedure for corneal specialists worldwide. Although the rate of complications has significantly been reduced, these can impede the long-term success, since some of them can be visually devastating. In an attempt to overcome these complications, researchers in the field have been recently working on improving the design of the currently available devices, by introducing the use of new materials that are more biocompatible with the eye. Here we present an update on the most recent research in the field.},
	issn = {2079-4983},
	doi = {10.3390/jfb7020013},
	author = {Salvador-Culla, Borja and Kolovou, Paraskevi E}
}
@article {688646,
	title = {Boston Keratoprosthesis Type 1 in Chemical Burns.},
	journal = {Cornea},
	volume = {35},
	number = {6},
	year = {2016},
	month = {2016 Jun},
	pages = {911-6},
	abstract = {PURPOSE: To describe and further analyze the long-term results in visual acuity (VA), anatomical retention, and rate of complications from patients who underwent Boston keratoprosthesis (B-Kpro) type 1 after ocular chemical burns in the Dominican Republic. METHODS: A retrospective review of 42 eyes (22 OD:20 OS) of 36 patients who underwent B-Kpro type 1 implantation after severe ocular burn at Hospital El{\'\i}as Santana in Santo Domingo, Dominican Republic, between April 2006 and October 2014, were included. RESULTS: Demographics, VA, anatomical retention, and the rates of postoperative complications and concurrent surgeries were evaluated. CONCLUSIONS: The excellent anatomical retention rates and visual outcomes presented in this study support the remarkable capability of B-Kpro type 1 to restore functional VA in eyes with severe chemical injuries. However, strict control of the postoperative complications is necessary for long-term success. In conclusion, the use of a B-Kpro type 1 after severe chemical burn is a viable option in patients otherwise condemned to the high risk of failure associated with conventional corneal grafts.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000837},
	author = {Salvador-Culla, Borja and Kolovou, Paraskevi E and Arzeno, Linnette and Mart{\'\i}nez, Santiago and L{\'o}pez, Miguel A}
}
@article {468931,
	title = {Galectin-8 Ameliorates Murine Autoimmune Ocular Pathology and Promotes a Regulatory T Cell Response.},
	journal = {PLoS One},
	volume = {10},
	number = {6},
	year = {2015},
	month = {2015},
	pages = {e0130772},
	abstract = {Galectins have emerged as potent immunoregulatory agents that control chronic inflammation through distinct mechanisms. Here, we report that treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis. Gal-8 treatment increased the number of regulatory T cells (Treg) in both the draining lymph node (dLN) and the inflamed retina. Moreover, a greater percentage of Treg cells in the dLN and retina of Gal-8 treated animals expressed the inhibitory coreceptor cytotoxic T lymphocyte antigen (CTLA)-4, the immunosuppressive cytokine IL-10, and the tissue-homing integrin CD103. Treg cells in the retina of Gal-8-treated mice were primarily inducible Treg cells that lack the expression of neuropilin-1. In addition, Gal-8 treatment blunted production of inflammatory cytokines by retinal T helper type (TH) 1 and TH17 cells. The effect of Gal-8 on T cell differentiation and/or function was specific for tissues undergoing an active immune response, as Gal-8 treatment had no effect on T cell populations in the spleen. Given the need for rational therapies for managing human uveitis, Gal-8 emerges as an attractive therapeutic candidate not only for treating retinal autoimmune diseases, but also for other TH1- and TH17-mediated inflammatory disorders.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0130772},
	author = {Sampson, James F and Hasegawa, Eiichi and Mulki, Lama and Suryawanshi, Amol and Jiang, Shuhong and Chen, Wei-Sheng and Rabinovich, Gabriel A and Connor, Kip M and Panjwani, Noorjahan}
}
@article {303966,
	title = {Characterization of full-length recombinant human Proteoglycan 4 as an ocular surface boundary lubricant},
	journal = {Exp Eye Res},
	volume = {127},
	year = {2014},
	month = {2014 Oct},
	pages = {14-9},
	abstract = {Proteoglycan 4 (PRG4, or lubricin) is a lubricating mucin-like glycoprotein recently discovered at the ocular surface, where it functions as a boundary lubricant and appears to play a protective role. Recent technological advances have enabled abundant expression of full-length recombinant human PRG4 (rhPRG4). The objectives of this study were to 1) biochemically characterize the gross structure and glycosylations of full-length rhPRG4, and 2) assess the ocular surface boundary lubricating ability of rhPRG4 at both human cornea-eyelid and human cornea-polydimethylsiloxane (PDMS) biointerfaces. rhPRG4 expressed by a Chinese hamster ovary cell line was characterized and compared to native bovine PRG4 by SDS-PAGE western blotting, and protein identity was assessed by tandem mass spectrometry (MS/MS). Human corneas were articulated against PDMS or human eyelids, at effective sliding velocities of 0.3-30\&nbsp;mm/s under physiological loads of \~{}15\&nbsp;kPa, to assess and compare the ocular lubricating ability of rhPRG4 to PRG4. Samples were tested serially in PRG4, rhPRG4 (both 300 μg/ml), then saline. Western blotting indicated that rhPRG4 had immunoreactivity at the appropriate apparent molecular weight, and possessed O-linked glycosylation consistent with that of PRG4. rhPRG4 protein identity was confirmed by MS/MS. Both PRG4 and rhPRG4 significantly, and similarly, reduced friction compared to saline at both human cornea - PDMS and human cornea-eyelid biointerfaces. In conclusion, the rhPRG4 studied here demonstrated appropriate higher order structure, O-linked glycosylations, and ocular surface boundary lubricating. Purified rhPRG4 may have clinical utility as a topical treatment of dry eye disease or contact lens biomaterial coating to promote more comfortable wear.},
	keywords = {Aged, Animals, Blotting, Western, CHO Cells, Cornea, Cricetulus, Dimethylpolysiloxanes, Electrophoresis, Polyacrylamide Gel, Eyelids, Friction, Glycosylation, Humans, Lubrication, Molecular Weight, Ophthalmic Solutions, Proteoglycans, Recombinant Proteins, Stress, Physiological, Surface Properties, Tandem Mass Spectrometry},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2014.06.015},
	author = {Samsom, Michael L and Morrison, Sheila and Masala, Nemanja and Sullivan, Benjamin D and Sullivan, David A and Sheardown, Heather and Schmidt, Tannin A}
}
@article {280906,
	title = {LKB1 and AMPK regulate synaptic remodeling in old age},
	journal = {Nat Neurosci},
	volume = {17},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1190-7},
	abstract = {Age-related decreases in neural function result in part from alterations in synapses. To identify molecular defects that lead to such changes, we focused on the outer retina, in which synapses are markedly altered in old rodents and humans. We found that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate this process. In old mice, synaptic remodeling was accompanied by specific decreases in the levels of total LKB1 and active (phosphorylated) AMPK. In the absence of either kinase, young adult mice developed retinal defects similar to those that occurred in old wild-type animals. LKB1 and AMPK function in rod photoreceptors where their loss leads to aberrant axonal retraction, the extension of postsynaptic dendrites and the formation of ectopic synapses. Conversely, increasing AMPK activity genetically or pharmacologically attenuates and may reverse age-related synaptic alterations. Together, these results identify molecular determinants of age-related synaptic remodeling and suggest strategies for attenuating these changes.},
	keywords = {Aging, Amacrine Cells, AMP-Activated Protein Kinases, Animals, Electroretinography, Female, Male, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation, Protein-Serine-Threonine Kinases, Retinal Bipolar Cells, Retinal Ganglion Cells, Rod Cell Outer Segment, Substrate Specificity, Synapses},
	issn = {1546-1726},
	doi = {10.1038/nn.3772},
	author = {Samuel, Melanie A and Voinescu, P Emanuela and Lilley, Brendan N and de Cabo, Rafa and Foretz, Marc and Viollet, Benoit and Pawlyk, Basil and Sandberg, Michael A and Vavvas, Demetrios G and Sanes, Joshua R}
}
@article {1351198,
	title = {Audio Haptic Videogaming for Developing Wayfinding Skills in Learners Who are Blind},
	journal = {IUI},
	volume = {2014},
	year = {2014},
	month = {2014},
	pages = {199-208},
	abstract = {Interactive digital technologies are currently being developed as a novel tool for education and skill development. Audiopolis is an audio and haptic based videogame designed for developing orientation and mobility (O\&amp;M) skills in people who are blind. We have evaluated the cognitive impact of videogame play on O\&amp;M skills by assessing performance on a series of behavioral tasks carried out in both indoor and outdoor virtual spaces. Our results demonstrate that the use of Audiopolis had a positive impact on the development and use of O\&amp;M skills in school-aged learners who are blind. The impact of audio and haptic information on learning is also discussed.},
	doi = {10.1145/2557500.2557519},
	author = {S{\'a}nchez, Jaime and de Borba Campos, Marcia and Espinoza, Mat{\'\i}as and Merabet, Lotfi B}
}
@article {1363211,
	title = {Enhancing Orientation and Mobility Skills in Learners who are Blind through Video gaming},
	journal = {Creat Cognit},
	volume = {2013},
	year = {2013},
	month = {2013},
	pages = {353-356},
	abstract = {In this work we present the results of the cognitive impact evaluation regarding the use of Audiopolis, an audio and/or haptic-based videogame. The software has been designed, developed and evaluated for the purpose of developing orientation and mobility (O\&amp;M) skills in blind users. The videogame was evaluated through cognitive tasks performed by a sample of 12 learners. The results demonstrated that the use of Audiopolis had a positive impact on the development and use of O\&amp;M skills in school-aged blind learners.},
	doi = {10.1145/2466627.2466673},
	author = {S{\'a}nchez, Jaime and Espinoza, Mat{\'\i}as and de Borba Campos, Marcia and Merabet, Lotfi B}
}
@article {303971,
	title = {The relationship of central foveal thickness to urinary iodine concentration in retinitis pigmentosa with or without cystoid macular edema.},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {10},
	year = {2014},
	month = {2014 Oct 1},
	pages = {1209-14},
	abstract = {IMPORTANCE: Current treatments for cystoid macular edema (CME) in retinitis pigmentosa (RP) are not always effective, may lead to adverse effects, and may not restore visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce CME in RP. OBJECTIVE: To determine whether central foveal thickness (CFT) in the presence of CME is related to dietary iodine intake inferred from urinary iodine concentration (UIC) in nonsmoking adults with RP. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional observational study of 212 nonsmoking patients aged 18 to 69 years referred to our institution for RP with visual acuity of no worse than 20/200 in at least 1 eye. EXPOSURE: Retinitis pigmentosa with or without CME. MAIN OUTCOMES AND MEASURES: With the eye as the unit of analysis, the relationship of log CFT measured by optical coherence tomography to UIC measured from multiple spot samples and represented as a 3-level classification variable (\&lt;100, 100-199, and >=200 {\textmu}g/L), assigning greater weight to patients with more reliable UIC estimates. RESULTS: Analyses were limited to 199 patients after excluding 11 who failed to return urine samples for measuring UIC and 2 outliers for UIC. Of the 199 patients, 36.2\% had CME in 1 or both eyes. Although log CFT was inversely related to UIC based on findings from all eyes (P = .02), regression of log CFT on UIC separately for eyes with and without CME showed a strong inverse significant relationship for the former group (P \&lt; .001) and no significant relationship for the latter group (P = .66) as tested. For the eyes with CME, CFT ranged from a geometric mean of 267 {\textmu}m for a median UIC of less than 100 {\textmu}g/L to a geometric mean of 172 {\textmu}m for a median UIC of 200 {\textmu}g/L or greater. In contrast, we found no significant association between CME prevalence and UIC based on the entire sample as tested (odds ratio, 1.01 [95\% CI, 0.38-2.67]; P = .99). CONCLUSIONS AND RELEVANCE: A higher UIC in nonsmoking adults with RP was significantly associated with less central foveal swelling in eyes with CME. Additional study is required to determine whether an iodine supplement can limit or reduce the extent of CME in patients with RP.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.1726},
	author = {Sandberg, Michael A and Pearce, Elizabeth N and Harper, Shyana and Weigel-DiFranco, Carol and Hart, Lois and Rosner, Bernard and Berson, Eliot L}
}
@article {303916,
	title = {Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, M{\"u}ller cells, lens, trabecular meshwork, cornea and lacrimal gland},
	journal = {Exp Eye Res},
	volume = {127},
	year = {2014},
	month = {2014 Oct},
	pages = {270-9},
	abstract = {This review highlights recent findings that describ how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca(2+) concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in M{\"u}ller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target may be a key issue in understanding how physiological signaling becomes pathological in ocular disease.},
	keywords = {Animals, Astrocytes, Cornea, Ependymoglial Cells, Eye, Eye Diseases, Humans, Lacrimal Apparatus, Lens, Crystalline, Purine Nucleosides, Purine Nucleotides, Retinal Neurons, Retinal Pigment Epithelium, Signal Transduction, Trabecular Meshwork},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2014.08.009},
	author = {Sanderson, Julie and Dartt, Darlene A. and Trinkaus-Randall, Vickery and Pintor, Jesus and Civan, Mortimer M and Delamere, Nicholas A and Fletcher, Erica L and Salt, Thomas E and Grosche, Antje and Mitchell, Claire H}
}
@article {1528419,
	title = {Immune checkpoint inhibitors and corneal transplant rejection: a call for awareness},
	journal = {Immunotherapy},
	volume = {12},
	number = {13},
	year = {2020},
	month = {2020 Sep},
	pages = {947-949},
	issn = {1750-7448},
	doi = {10.2217/imt-2020-0100},
	author = {Sandhu, Harpal Singh and Hemmati, Houman D and Dana, Reza}
}
@article {1452956,
	title = {GRA15 Activates the NF-κB Pathway through Interactions with TNF Receptor-Associated Factors},
	journal = {MBio},
	volume = {10},
	number = {4},
	year = {2019},
	month = {2019 Jul 16},
	abstract = {The protozoan parasite secretes proteins from specialized organelles, the rhoptries, and dense granules, which are involved in the modulation of host cell processes. Dense granule protein GRA15 activates the nuclear factor kappa B (NF-κB) pathway, which plays an important role in cell death, innate immunity, and inflammation. Exactly how GRA15 activates the NF-κB pathway is unknown. Here we show that GRA15 interacts with tumor necrosis factor receptor-associated factors (TRAFs), which are adaptor proteins functioning upstream of the NF-κB transcription factor. We identified several TRAF binding sites in the GRA15 amino acid sequence and showed that these are involved in NF-κB activation. Furthermore, a TRAF2 knockout cell line has impaired GRA15-mediated NF-κB activation. Thus, we determined the mechanism for GRA15-dependent NF-κB activation. The parasite can cause birth defects and severe disease in immunosuppressed patients. Strain differences in pathogenicity exist, and these differences are due to polymorphic effector proteins that secretes into the host cell to coopt host cell functions. The effector protein GRA15 of some strains activates the nuclear factor kappa B (NF-κB) pathway, which plays an important role in cell death, innate immunity, and inflammation. We show that GRA15 interacts with TNF receptor-associated factors (TRAFs), which are adaptor proteins functioning upstream of the NF-κB transcription factor. Deletion of TRAF-binding sites in GRA15 greatly reduces its ability to activate the NF-κB pathway, and TRAF2 knockout cells have impaired GRA15-mediated NF-κB activation. Thus, we determined the mechanism for GRA15-dependent NF-κB activation.},
	issn = {2150-7511},
	doi = {10.1128/mBio.00808-19},
	author = {Sangar{\'e}, Lamba Omar and Yang, Ninghan and Konstantinou, Eleni K and Lu, Diana and Mukhopadhyay, Debanjan and Young, Lucy H and Saeij, Jeroen P J}
}
@article {1658682,
	title = {Identification of a novel large multigene deletion and a frameshift indel in PDE6B as the underlying cause of early-onset recessive rod-cone degeneration},
	journal = {Cold Spring Harb Mol Case Stud},
	volume = {8},
	number = {7},
	year = {2022},
	month = {2022 Dec},
	abstract = {A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the PDE6B gene in the affected twins and their unaffected father. Further investigation, using genome sequencing, identified a novel \~{}7.5-kb deletion (Chr 4:670,405-677,862del) encompassing the ATP5ME gene, part of the 5{\textquoteright} UTR of MYL5, and a 378-bp (Chr 4:670,405-670,782) region from the 3{\textquoteright} UTR of PDE6B in the affected twins and their unaffected mother. Both variants segregated with disease in the family. Analysis of the relative expression of PDE6B, in peripheral blood cells, also revealed a significantly lower level of PDE6B transcript in affected siblings compared to a normal control. PDE6B is associated with recessive rod-cone degeneration and autosomal dominant congenital stationary night blindness. Ophthalmic evaluation of these patients showed night blindness, fundus abnormalities, and peripheral vision loss, which are consistent with PDE6B-associated recessive retinal degeneration. These findings suggest that the loss of PDE6B transcript resulting from the compound heterozygous pathogenic variants is the underlying cause of recessive rod-cone degeneration in the study family.},
	keywords = {Blindness, Cyclic Nucleotide Phosphodiesterases, Type 6, Frameshift Mutation, Humans, INDEL Mutation, Mutation, Night Blindness, Pedigree, Retinal Degeneration},
	issn = {2373-2873},
	doi = {10.1101/mcs.a006247},
	author = {Sangermano, Riccardo and Biswas, Pooja and Sullivan, Lori S and Place, Emily M and Borooah, Shyamanga and Straubhaar, Juerg and Pierce, Eric A and Daiger, Stephen P and Bujakowska, Kinga M and Ayaggari, Radha}
}
@article {1598069,
	title = {Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD},
	journal = {NPJ Genom Med},
	volume = {6},
	number = {1},
	year = {2021},
	month = {2021 Jun 29},
	pages = {53},
	abstract = {Pathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E. Additional two patients showed early onset IRD with limited JBTS features. Detailed phenotypic description for all probands is presented. We report 14 rare INPP5E variants, 12 of which have not been reported in previous studies. We present tertiary protein modeling and analyze all INPP5E variants for deleteriousness and phenotypic correlation. We observe that the combined impact of INPP5E variants in JBTS and non-syndromic IRD patients does not reveal a clear genotype-phenotype correlation, suggesting the involvement of genetic modifiers. Our study cements the wide phenotypic spectrum of INPP5E disease, adding proof that sequence defects in this gene can lead to early-onset non-syndromic IRD.},
	issn = {2056-7944},
	doi = {10.1038/s41525-021-00214-8},
	author = {Sangermano, Riccardo and Deitch, Iris and Peter, Virginie G and Ba-Abbad, Rola and Place, Emily M and Zampaglione, Erin and Wagner, Naomi E and Fulton, Anne B and Coutinho-Santos, Luisa and Rosin, Boris and Dunet, Vincent and AlTalbishi, Ala{\textquoteright}a and Banin, Eyal and Sousa, Ana Berta and Neves, Mariana and Larson, Anna and Quinodoz, Mathieu and Michaelides, Michel and Ben-Yosef, Tamar and Pierce, Eric A and Rivolta, Carlo and Webster, Andrew R and Arno, Gavin and Sharon, Dror and Huckfeldt, Rachel M and Bujakowska, Kinga M}
}
@article {439701,
	title = {Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration.},
	journal = {PLoS One},
	volume = {10},
	number = {5},
	year = {2015},
	month = {2015},
	pages = {e0125548},
	abstract = {We conducted a nested candidate gene study and pathway-based enrichment analysis on data from a multi-national 77,000-person project on the molecular genetics of age-related macular degeneration (AMD) to identify AMD-associated DNA-sequence variants in genes encoding constituents of a netrin-1 (NTN1)-based signaling pathway that converges on DNA-binding transcription complexes through a 3{\textquoteright}-5{\textquoteright}-cyclic adenosine monophosphate-calcineurin (cAMP-CN)-dependent axis. AMD-associated single nucleotide polymorphisms (SNPs) existed in 9 linkage disequilibrium-independent genomic regions; these included loci overlapping NTN1 (rs9899630, P <= 9.48 x 10-5), DCC (Deleted in Colorectal Cancer)-the gene encoding a primary NTN1 receptor (rs8097127, P <= 3.03 x 10-5), and 6 other netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods demonstrated robust enrichment with AMD-associated SNPs (corrected P-value = 0.038), supporting the idea that processes driven by NTN1-DCC signaling systems operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved drugs and may offer promise for guiding applied clinical research on preventive and therapeutic interventions for AMD.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0125548},
	author = {SanGiovanni, John Paul and Chen, Jing and Gupta, Ankur S and Smith, Lois E H and Sapieha, Przemyslaw and Lee, Phil H}
}
@article {1287976,
	title = {Two-Way Social Media Messaging in Postoperative Cataract Surgical Patients: Prospective Interventional Study},
	journal = {J Med Internet Res},
	volume = {19},
	number = {12},
	year = {2017},
	month = {2017 Dec 19},
	pages = {e413},
	abstract = {BACKGROUND: Social media offers a new way to provide education, reminders, and support for patients with a variety of health conditions. Most of these interventions use one-way, provider-patient communication. Incorporating social media tools to improve postoperative (postop) education and follow-up care has only been used in limited situations. OBJECTIVE: The aim of this study was to determine the feasibility and efficacy of two-way social media messaging to deliver reminders and educational information about postop care to cataract patients. METHODS: A total of 98 patients undergoing their first eye cataract surgery were divided into two groups: a no message group receiving usual pre- and postop care and a message group receiving usual care plus messages in a mobile social media format with standardized content and timing. Each patient in the message group received nine messages about hand and face hygiene, medication and postop visit adherence, and links to patient education videos about postop care. Patients could respond to messages as desired. Main outcome measures included medication adherence, postop visit adherence, clinical outcomes, and patients{\textquoteright} subjective assessments of two-way messaging. The number, types, content, and timing of responses by patients to messages were recorded. RESULTS: Medication adherence was better in the message group at postop day 7, with high adherence in 47 patients (96\%, 47/49) versus 36 patients (73\%, 36/49) in the no message group (P=.004), but no statistically significant differences in medication adherence between the groups were noted at preop and postop day 30. Visit adherence was higher at postop day 30 in the message group (100\%, 49/49) versus the no message group (88\%, 43/49; P=.03) but was 100\% (49/49) in both groups at postop day 1 and 7. Final visual outcomes were similar between groups. A total of 441 standardized messages were sent to the message group. Out of 270 responses generated, 188 (70\%) were simple acknowledgments or "thank you," and 82 (30\%) responses were questions that were divided into three general categories: administrative, postop care, and clinical issues. Out of the 82 question responses, 31 (11\%) were about administrative issues, 28 (10\%) about postop care, and 23 (9\%) about clinical symptoms. All the messages about symptoms were triaged by nurses or ophthalmologists and only required reassurance or information. Patients expressed satisfaction with messaging. CONCLUSIONS: Two-way social media messaging to deliver postop information to cataract patients is feasible and improves early medication compliance. Further design improvements can streamline work flow to optimize efficiency and patient satisfaction.},
	issn = {1438-8871},
	doi = {10.2196/jmir.8330},
	author = {Sanguansak, Thuss and Morley, Katharine E and Morley, Michael G and Thinkhamrop, Kavin and Thuanman, Jaruwan and Agarwal, Isha}
}
@article {1653575,
	title = {Retinoic acid delays initial photoreceptor differentiation and results in a highly structured mature retinal organoid},
	journal = {Stem Cell Res Ther},
	volume = {13},
	number = {1},
	year = {2022},
	month = {2022 09 16},
	pages = {478},
	abstract = {BACKGROUND: Human-induced pluripotent stem cell-derived retinal organoids are a valuable tool for disease modelling and therapeutic development. Many efforts have been made over the last decade to optimise protocols for the generation of organoids that correctly mimic the human retina. Most protocols use common media supplements; however, protocol-dependent variability impacts data interpretation. To date, the lack of a systematic comparison of a given protocol with or without supplements makes it difficult to determine how they influence the differentiation process and morphology of the retinal organoids. METHODS: A\&nbsp;2D-3D differentiation method was used\&nbsp;to generate retinal organoids, which were cultured with or without the most commonly used media supplements, notably retinoic acid. Gene expression was assayed using qPCR analysis, protein expression using immunofluorescence studies, ultrastructure using electron microscopy and 3D morphology using confocal and biphoton microscopy of whole organoids. RESULTS: Retinoic acid delayed the initial stages of differentiation by modulating photoreceptor gene expression. At later stages, the presence of retinoic acid led to the generation of mature retinal organoids with a well-structured stratified photoreceptor layer containing a predominant rod population. By contrast, the absence of retinoic acid led to cone-rich organoids with a less organised and non-stratified photoreceptor layer. CONCLUSIONS: This\&nbsp;study proves the importance of supplemented media for culturing retinal organoids. More importantly, we demonstrate for the first time that the role of retinoic acid goes beyond inducing a rod cell fate to enhancing the organisation of the photoreceptor layer of the mature organoid.},
	keywords = {Cell Differentiation, Humans, Induced Pluripotent Stem Cells, Organoids, Retina, Tretinoin},
	issn = {1757-6512},
	doi = {10.1186/s13287-022-03146-x},
	author = {Sanjurjo-Soriano, Carla and Erkilic, Nejla and Damodar, Krishna and Boukhaddaoui, Hassan and Diakatou, Michalitsa and Garita-Hernandez, Marcela and Mamaeva, Daria and Dubois, Gregor and Jazouli, Zhour and Jimenez-Medina, Carla and Goureau, Olivier and Meunier, Isabelle and Kalatzis, Vasiliki}
}
@article {314186,
	title = {Compound-gene interaction mapping reveals distinct roles for Staphylococcus aureus teichoic acids},
	journal = {Proc Natl Acad Sci U S A},
	volume = {111},
	number = {34},
	year = {2014},
	month = {2014 Aug 26},
	pages = {12510-5},
	abstract = {Staphylococcus aureus contains two distinct teichoic acid (TA) polymers, lipoteichoic acid (LTA) and wall teichoic acid (WTA), which are proposed to play redundant roles in regulating cell division. To gain insight into the underlying biology of S. aureus TAs, we used a small molecule inhibitor to screen a highly saturated transposon library for cellular factors that become essential when WTA is depleted. We constructed an interaction network connecting WTAs with genes involved in LTA synthesis, peptidoglycan synthesis, surface protein display, and D-alanine cell envelope modifications. Although LTAs and WTAs are synthetically lethal, we report that they do not have the same synthetic interactions with other cell envelope genes. For example, D-alanylation, a tailoring modification of both WTAs and LTAs, becomes essential when the former, but not the latter, are removed. Therefore, D-alanine-tailored LTAs are required for survival when WTAs are absent. Examination of terminal phenotoypes led to the unexpected discovery that cells lacking both LTAs and WTAs lose their ability to form Z rings and can no longer divide. We have concluded that the presence of either LTAs or WTAs on the cell surface is required for initiation of S. aureus cell division, but these polymers act as part of distinct cellular networks.},
	keywords = {Alanine, Cell Division, Cell Wall, Chromosome Mapping, DNA Transposable Elements, Gene Knockout Techniques, Gene Regulatory Networks, Genes, Bacterial, Lipopolysaccharides, Mutation, Phenotype, Staphylococcus aureus, Teichoic Acids},
	issn = {1091-6490},
	doi = {10.1073/pnas.1404099111},
	author = {Santa Maria, John P and Sadaka, Ama and Moussa, Samir H and Brown, Stephanie and Zhang, Yanjia J and Rubin, Eric J and Gilmore, Michael S and Walker, Suzanne}
}
@article {1351182,
	title = {Influence of diabetes and diabetes type on anatomic and visual outcomes following central rein vein occlusion},
	journal = {Eye (Lond)},
	volume = {28},
	number = {3},
	year = {2014},
	month = {2014 Mar},
	pages = {259-68},
	abstract = {PURPOSE: To determine the influence of diabetes and diabetes type on ocular outcomes following central retinal vein occlusion (CRVO). METHODS: Retrospective chart review of all patients evaluated over a 4-year period in a tertiary diabetes eye care center. Ophthalmic findings were recorded including visual acuity and the presence of retinal neovascularization at presentation, after 3-6 months, and at last follow-up. RESULTS: The records of 19,648 patients (13,571 diabetic; 6077 nondiabetic) were reviewed. The prevalence of CRVO in diabetic patients (N=72) and nondiabetic patients (N=27) were 0.5 and 0.4\%, respectively. Disc neovascularization (21.3 vs 0.0\%, P=0.05) and panretinal photocoagulation (PRP) (48.7 vs 21.4\%, P=0.01) were more common in diabetic patients compared with nondiabetic patients. Compared with type 2 diabetic patients, retinal neovascularization (28.6 vs 3.7\%, P=0.004) and subsequent PRP (78.6 vs 41.9\%, P=0.01) were more likely in type 1 patients. Optic nerve head collateral vessels (CVs) were observed less than half as often (21.4 vs 56.5\%, P=0.04) in patients with type 1 diabetes. Presence of optic nerve head CVs at baseline was associated with less likelihood of PRP (14.3 vs 46.1\%, P=0.03). CONCLUSIONS: In this cohort, the rates of CRVO in diabetic and nondiabetic patients were similar to previously published population-based studies. Following CRVO, diabetic patients had higher rates of disc neovascularization and were more likely to require subsequent PRP than nondiabetic patients. As compared with CRVO patients with type 2 diabetes, patients with type 1 diabetes and CRVO had worse anatomic outcomes with substantially increased risks of retinal neovascularization and PRP; however, final visual acuity outcomes were similar.},
	keywords = {Adult, Aged, Aged, 80 and over, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Fluorescein Angiography, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Laser Coagulation, Male, Middle Aged, Retinal Neovascularization, Retinal Vein Occlusion, Retrospective Studies, Risk Factors, Visual Acuity},
	issn = {1476-5454},
	doi = {10.1038/eye.2014.1},
	author = {Santiago, J G and Walia, S and Sun, J K and Cavallerano, J D and Haddad, Z A and Aiello, L P and Silva, P S}
}
@article {1364539,
	title = {Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice},
	journal = {Nutr Diabetes},
	volume = {2},
	year = {2012},
	month = {2012 Jul 23},
	pages = {e36},
	abstract = {OBJECTIVE: Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). DESIGN: Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks-26 weeks of life) on calorically and compositionally matched diets, except for 2\% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. RESULTS: The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. CONCLUSION: This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM.},
	issn = {2044-4052},
	doi = {10.1038/nutd.2012.10},
	author = {Sapieha, P and Chen, J and Stahl, A and Seaward, M R and Favazza, T L and Juan, A M and Hatton, C J and Joyal, J-S and Krah, N M and Dennison, R J and Tang, J and Kern, T S and Akula, J D and Smith, L.E.H}
}
@article {1806691,
	title = {In vivo quasi-elastic light scattering detects molecular changes in the lenses of adolescents with Down syndrome},
	journal = {Exp Eye Res},
	volume = {241},
	year = {2024},
	month = {2024 Feb 02},
	pages = {109818},
	abstract = {Down syndrome (DS) is the most common chromosomal disorder in humans. DS is associated with increased prevalence of several ocular sequelae, including characteristic blue-dot cerulean cataract. DS is accompanied by age-dependent accumulation of Alzheimer{\textquoteright}s disease (AD) amyloid-β (Aβ) peptides and amyloid pathology in the brain and comorbid early-onset Aβ amyloidopathy and colocalizing cataracts in the lens. Quasi-elastic light scattering (QLS) is an established optical technique that noninvasively measures changes in protein size distributions in the human lens in vivo. In this cross-sectional study, lenticular QLS correlation time was decreased in adolescent subjects with DS compared to age-matched control subjects. Clinical QLS was consistent with alterations in relative particle hydrodynamic radius in lenses of adolescents with DS. These correlative results suggest that noninvasive QLS can be used to evaluate molecular changes in the lenses of individuals with DS.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2024.109818},
	author = {Sarangi, Srikant and Minaeva, Olga and Ledoux, Danielle M and Parsons, Douglas S and Moncaster, Juliet A and Black, Caitlin A and Hollander, Jeffrey and Tripodis, Yorghos and Clark, John I and Hunter, David G and Goldstein, Lee E}
}
@article {560181,
	title = {Mitochondrial Profile and Responses to TGF-β Ligands in Keratoconus.},
	journal = {Curr Eye Res},
	volume = {41},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {900-7},
	abstract = {PURPOSE: Keratoconus (KC) is a complex corneal dystrophy with multifactorial etiology. Previous studies have shown evidence of mitochondrial abnormalities in KC; however, the exact cause of these abnormalities remains unknown. The aim of this study was to identify if transforming growth factor-β (TGF-β) isoforms play a role in the regulation of mitochondrial proteins in human KC cells (HKC). MATERIALS AND METHODS: Human corneal fibroblasts (HCF) and HKC were isolated and cultured for 4 weeks in three different conditions: (a) CONTROL: MEM + 10\%FBS, (b) MEM + 10\%FBS + TGF-β1 and (c) MEM + 10\%FBS + TGF-β3. All samples were processed for mitochondrial damage analysis using real-time PCR. RESULTS: We quantified and analyzed 84 mitochondrial and five housekeeping genes in HCFs and HKCs. Our data showed that when TGF-β1 and/or TGF-β3 were compared with control in HCFs, nine genes were significantly different; however, no genes were significantly regulated by the TGF-β isoforms in HKCs. Significant differences were also seen in seven genes when HFCs were compared with HKCs, in all three conditions. CONCLUSIONS: Overall, our data support the growing consensus that mitochondrial dysfunction is a key player in KC disease. These in vitro data show clear links between mitochondrial function and TGF-β isoforms, with TGF-β1 severely disrupting KC-mitochondrial function, while TGF-β3 maintained it, thus suggesting that TGF-β may play a role in KC-disease treatment.},
	issn = {1460-2202},
	doi = {10.3109/02713683.2015.1078361},
	author = {Sarker-Nag, Akhee and Hutcheon, Audrey E K and Karamichos, Dimitrios}
}
@article {1351183,
	title = {Transcriptional response of Enterococcus faecalis to sunlight},
	journal = {J Photochem Photobiol B},
	volume = {130},
	year = {2014},
	month = {2014 Jan 05},
	pages = {349-56},
	abstract = {Microarrays were used to investigate the transcriptional response of Enterococcus faecalis to photostress. E. faecalis are Gram-positive bacteria used as indicators of water quality and have been shown to vary diurnally in response to sunlight. E. faecalis in filtered seawater microcosms were exposed to artificial sunlight for 12h and then placed in the dark for 12h. Transcript abundance was measured at 0, 2, 6, 12, and 24h in the sunlit microcosm and a dark control using microarrays. Culturable E. faecalis concentrations decreased 6-7 orders of magnitude within the first 6h of light exposure. After 12h in the dark, no evidence of dark-repair was observed. Expression data collected after 12h of sunlight exposure revealed a difference in transcript abundance in the light relative to dark microcosms for 35 unique ORFs, 33 ORFs showed increased transcript abundance and 2 ORFs showed reduced transcript abundance. A majority (51\%) of the ORFs with increased transcript abundance in the sunlit relative to dark microcosms encoded hypothetical proteins; others were associated with protein synthesis, oxidative stress and DNA repair. Results suggest that E. faecalis exposed to sunlight actively transcribe RNA in response to photostress.},
	keywords = {Bacterial Proteins, DNA Damage, DNA Repair, Enterococcus faecalis, Gene Expression Regulation, Bacterial, Oligonucleotide Array Sequence Analysis, Open Reading Frames, RNA, Messenger, Stress, Physiological, Sunlight, Transcription, Genetic},
	issn = {1873-2682},
	doi = {10.1016/j.jphotobiol.2013.12.013},
	author = {Sassoubre, Lauren M and Ramsey, Matthew M and Gilmore, Michael S and Boehm, Alexandria B}
}
@article {1078811,
	title = {Determinants of Ocular Pain Severity in Patients With Dry Eye Disease},
	journal = {Am J Ophthalmol},
	volume = {179},
	year = {2017},
	month = {2017 Jul},
	pages = {198-204},
	abstract = {PURPOSE: To quantify the severity of ocular pain in patients with dry eye disease (DED) and evaluate factors associated with pain severity. DESIGN: Cross-sectional study. METHODS: Eighty-four patients with DED were asked to score their severity level of ocular pain using a 10-point scale, with 10 indicating the most severe pain. All patients also had a comprehensive ophthalmic assessment including a detailed history, Ocular Surface Disease Index (OSDI) questionnaire, and ocular surface examination. Regression analysis was used to determine the factors associated with ocular pain severity. RESULTS: The mean OSDI score was 45.6 {\textpm} 23.1. At least some degree of ocular pain (score \&gt;1) was reported by 88.1\% of patients, including mild pain (scores 2-4) in 46.4\%, moderate pain (scores 5-7) in 34.5\%, and severe pain (scores 8-10) in 7.1\% of patients. Ocular pain levels significantly correlated with the OSDI score (rs\&nbsp;= 0.49, P \&lt; .001). Regression analysis showed that the severity of ocular pain had a significant association with use of antidepressant medications (P\&nbsp;= .045) but not with tear breakup time, corneal fluorescein staining, or ocular medications used by patients. In patients without pain, a significant correlation was seen between OSDI and corneal fluorescein staining scores (rs\&nbsp;= 0.67, P\&nbsp;=\&nbsp;.01). However, such a correlation was not observed in those with ocular pain. CONCLUSIONS: A majority of patients with DED report some degree of ocular pain, which correlates only moderately with the OSDI score. Severity of ocular pain correlates with nonocular comorbidities such as use of antidepressant medications rather than with clinical signs of DED.},
	keywords = {Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Dry Eye Syndromes, Eye Pain, Female, Humans, Incidence, Male, Massachusetts, Middle Aged, Pain Measurement, Severity of Illness Index, Surveys and Questionnaires, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.05.009},
	author = {Satitpitakul, Vannarut and Kheirkhah, Ahmad and Crnej, Alja and Hamrah, Pedram and Dana, Reza}
}
@article {1328901,
	title = {Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival},
	journal = {Am J Pathol},
	volume = {188},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {2016-2024},
	abstract = {Corneal transplantation is the most prevalent form of tissue transplantation. The success of corneal transplantation mainly relies on the integrity of corneal endothelial cells (CEnCs), which maintain graft transparency. CEnC density decreases significantly after corneal transplantation even in the absence of graft rejection. To date, different strategies have been used to enhance CEnC survival. The neuropeptide vasoactive intestinal peptide (VIP) improves CEnC integrity during donor cornea tissue storage and protects CEnCs against oxidative stress-induced apoptosis. However, little is known about the effect of\&nbsp;exogenous administration of VIP on corneal transplant outcomes. We found that VIP significantly\&nbsp;accelerates endothelial wound closure and suppresses interferon-γ- and tumor necrosis factor-α-induced CEnC apoptosis in\&nbsp;vitro in a dose-dependent manner. In addition, we found that intracameral administration of VIP to mice undergoing syngeneic corneal transplantation with endothelial injury increases CEnC density and decreases graft opacity scores. Finally, using a mouse model of allogeneic corneal transplantation, we found for the first time that treatment with VIP significantly suppresses posttransplantation CEnC loss and improves corneal allograft survival.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2018.05.010},
	author = {Satitpitakul, Vannarut and Sun, Zhongmou and Suri, Kunal and Amouzegar, Afsaneh and Katikireddy, Kishore R and Jurkunas, Ula V and Kheirkhah, Ahmad and Dana, Reza}
}
@article {1798446,
	title = {Detection of Copy-Number Variation in Circulating Cell-Free DNA in Patients With Uveal Melanoma},
	journal = {JCO Precis Oncol},
	volume = {8},
	year = {2024},
	month = {2024 Jan},
	pages = {e2300368},
	abstract = {PURPOSE: Somatic chromosomal alterations, particularly monosomy 3 and 8q gains, have been associated with metastatic risk in uveal melanoma (UM). Whole genome-scale evaluation of detectable alterations in cell-free DNA (cfDNA) in UM could provide valuable prognostic information. Our pilot study evaluates the correlation between genomic information using ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA in UM and associated clinical outcomes.

MATERIALS AND METHODS: ULP-WGS of cfDNA was performed on 29 plasma samples from 16 patients, 14 metastatic UM (mUM) and two non-metastatic, including pre- and post-treatment mUM samples from 10 patients treated with immunotherapy and one with liver-directed therapy. We estimated tumor fraction (TFx) and detected copy-number alterations (CNAs) using ichorCNA. Presence of 8q amplification was further analyzed using the likelihood ratio test (LRT).

RESULTS: Eleven patients with mUM (17 samples) of 14 had detectable circulating tumor DNA (ctDNA). 8q gain was detected in all 17, whereas monosomy 3 was detectable in 10 of 17 samples. TFx generally correlated with disease status, showing an increase at the time of disease progression (PD). 8q gain detection sensitivity appeared greater with the LRT than with ichorCNA at lower TFxs. The only patient with mUM with partial response on treatment had a high pretreatment TFx and undetectable on-treatment ctDNA, correlating with her profound response and durable survival.

CONCLUSION: ctDNA can be detected in mUM using ULP-WGS, and the TFx correlates with DS. 8q gain was consistently detectable in mUM, in line with previous studies indicating 8q gains early in primary UM and higher amplification with PD. Our work suggests that detection of CNAs by ULP-WGS, particularly focusing on 8q gain, could be a valuable blood biomarker to monitor PD in UM.},
	keywords = {Circulating Tumor DNA, Female, Humans, Melanoma, Monosomy, Pilot Projects, Uveal Neoplasms},
	issn = {2473-4284},
	doi = {10.1200/PO.23.00368},
	author = {Sato, Takuto and Montazeri, Kamaneh and Gragoudas, Evangelos S and Lane, Anne Marie and Aronow, Mary Beth and Cohen, Justine V and Boland, Genevieve M and Banks, Eric and Kachulis, Christopher and Fleharty, Mark and Cibulskis, Carrie and Lawless, Aleigha and Adalsteinsson, Viktor A and Sullivan, Ryan J and Kim, Ivana K}
}
@article {931156,
	title = {Invariant natural killer T cells play dual roles in the development of experimental autoimmune uveoretinitis.},
	journal = {Exp Eye Res},
	volume = {153},
	year = {2016},
	month = {2016 Dec},
	pages = {79-89},
	abstract = {Experimental autoimmune uveoretinitis (EAU) represents an experimental model for human endogenous uveitis, which is caused by Th1/Th17 cell-mediated inflammation. Natural killer T (NKT) cells recognize lipid antigens and produce large amounts of cytokines upon activation. To examine the role of NKT cells in the development of uveitis, EAU was elicited by immunization with a peptide from the human interphotoreceptor retinoid-binding protein (hIRBP1-20) in complete Freund{\textquoteright}s adjuvant and histopathology scores were evaluated in C57BL/6 (WT) and NKT cell-deficient mice. NKT cell-deficient mice developed more severe EAU pathology than WT mice. When WT mice were treated with ligands of the invariant subset of NKT cells (α-GalCer or RCAI-56), EAU was ameliorated in mice treated with RCAI-56 but not α-GalCer. IRBP-specific Th1/Th17 cytokines were reduced in RCAI-56-treated compared with vehicle-treated mice. Although the numbers of IRBP-specific T cells detected by hIRBP3-13/I-A(b) tetramers in the spleen and the draining lymph node were the same for vehicle and RCAI-56 treatment groups, RORγt expression by tetramer-positive cells in RCAI-56-treated mice was lower than in control mice. Moreover, the eyes of RCAI-56-treated mice contained fewer IRBP-specific T cells compared with control mice. These results suggest that invariant NKT (iNKT) cells suppress the induction of Th17 cells and infiltration of IRBP-specific T cells into the eyes, thereby reducing ocular inflammation. However, in sharp contrast to the ameliorating effects of iNKT cell activation during the initiation phase of EAU, iNKT cell activation during the effector phase exacerbated disease pathology. Thus, we conclude that iNKT cells exhibit dual roles in the development of EAU.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2016.10.003},
	author = {Satoh, Masashi and Namba, Ken-Ichi and Kitaichi, Nobuyoshi and Endo, Noriko and Kitamei, Hirokuni and Iwata, Daiju and Ohno, Shigeaki and Ishida, Susumu and Ono{\'e}, Kazunori and Watarai, Hiroshi and Taniguchi, Masaru and Ishibashi, Tatsuro and Stein-Streilein, Joan and Sonoda, Koh-Hei and Van Kaer, Luc and Iwabuchi, Kazuya}
}
@article {1452973,
	title = {Photoablation of Human Vitreous Opacities by Light-Induced Vapor Nanobubbles},
	journal = {ACS Nano},
	volume = {13},
	number = {7},
	year = {2019},
	month = {2019 Jul 23},
	pages = {8401-8416},
	abstract = {Myopia, diabetes, and aging are the main causes of progressive vitreous collagen aggregation, resulting in vitreous opacities, which can significantly disturb vision. As vitreous opacities, which induce the visual phenomenon of "floaters", are accessible with nanomaterials and light, we propose a nanotechnology-based approach to locally ablate them with highly reduced light energy compared to the more traditional YAG laser therapy. Our strategy relies on the plasmon properties of gold nanoparticles that generate vapor nanobubbles upon pulsed-laser illumination whose mechanical force can ablate vitreous opacities. We designed gold nanoparticles coated with hyaluronic acid (HA), which have excellent diffusional mobility in human vitreous, an essential requirement to reach the vitreous opacities. In addition, we found that HA-coated gold nanoparticles can accumulate extensively on human vitreous opacities that were obtained by vitrectomy from patients with vision-degrading myodesopsia. When subsequently applying nanosecond laser pulses, the collagen aggregates were efficiently destroyed with \~{}1000 times less light energy than typically used in YAG laser therapy. This low-energy "floater-specific destruction", which is due to the accumulation of the small gold nanoparticles on the opacities, is attractive, as it may be safer to the surrounding ocular tissues while at the same time being easier and faster to apply compared to YAG laser therapy, where the opacities need to be ablated piece by piece by a tightly focused laser beam. Gold nanoparticle-assisted photoablation may therefore provide a safer, faster, and more reliable destruction of vitreous opacities in the treatment of ophthalmologic diseases.},
	issn = {1936-086X},
	doi = {10.1021/acsnano.9b04050},
	author = {Sauvage, F{\'e}lix and Fraire, Juan C and Remaut, Katrien and Sebag, J and Peynshaert, Karen and Harrington, Michael and Van de Velde, Frans J and Xiong, Ranhua and Tassignon, Marie-Jos{\'e} and Brans, Toon and Braeckmans, Kevin and De Smedt, Stefaan C}
}
@article {1417575,
	title = {The effects of age and cognitive load on peripheral-detection performance},
	journal = {J Vis},
	volume = {19},
	number = {1},
	year = {2019},
	month = {2019 Jan 02},
	pages = {15},
	abstract = {Age-related declines in both peripheral vision and cognitive resources could contribute to the increased crash risk of older drivers. However, it is unclear whether increases in age and cognitive load result in equal detriments to detection rates across all peripheral target eccentricities (general interference effect) or whether these detriments become greater with increasing eccentricity (tunnel effect). In the current study we investigated the effects of age and cognitive load on the detection of peripheral motorcycle targets (at 5{\textdegree}-30{\textdegree} eccentricity) in static images of intersections. We used a dual-task paradigm in which cognitive load was manipulated without changing the complexity of the central (foveal) visual stimulus. Each image was displayed briefly (250 ms) to prevent eye movements. When no cognitive load was present, age resulted in a tunnel effect; however, when cognitive load was high, age resulted in a general interference effect. These findings suggest that tunnel and general interference effects can co-occur and that the predominant effect varies with the level of demand placed on participants{\textquoteright} resources. High cognitive load had a general interference effect in both age groups, but the effect attenuated at large target eccentricities (opposite of a tunnel effect). Low cognitive load had a general interference effect in the older but not the younger group, impairing detection of motorcycle targets even at 5{\textdegree} eccentricity, which could present an imminent collision risk in real driving.},
	issn = {1534-7362},
	doi = {10.1167/19.1.15},
	author = {Savage, Steven W and Spano, Lauren P and Bowers, Alex R}
}
@article {1528409,
	title = {The effects of age on the contributions of head and eye movements to scanning behavior at intersections},
	journal = {Transp Res Part F Traffic Psychol Behav},
	volume = {73},
	year = {2020},
	month = {2020 Aug},
	pages = {128-142},
	abstract = {The current study was aimed at evaluating the effects of age on the contributions of head and eye movements to scanning behavior at intersections. When approaching intersections, a wide area has to be scanned requiring large lateral head rotations as well as eye movements. Prior research suggests older drivers scan less extensively. However, due to the wide-ranging differences in methodologies and measures used in prior research, the extent to which age-related changes in eye or head movements contribute to these deficits is unclear. Eleven older (mean 67 years) and 18 younger (mean 27 years) current drivers drove in a simulator while their head and eye movements were tracked. Scans, analyzed for 15 four-way intersections in city drives, were split into two categories: (consisting only of eye movements) and (containing both head and eye movements). Older drivers made smaller scans than younger drivers (46.6{\textdegree} vs. 53{\textdegree}), as well as smaller scans (9.2{\textdegree} vs. 10.1{\textdegree}), resulting in overall smaller scans. For scans, older drivers had both a smaller head and a smaller eye movement component. Older drivers made more scans than younger drivers (7 vs. 6) but fewer scans (2.1 vs. 2.7). This resulted in no age effects when considering scans. Our results clarify the contributions of eye and head movements to age-related deficits in scanning at intersections, highlight the importance of analyzing both eye and head movements, and suggest the need for older driver training programs that emphasize the importance of making large scans before entering intersections.},
	issn = {1369-8478},
	doi = {10.1016/j.trf.2020.06.015},
	author = {Savage, Steven W and Zhang, Lily and Swan, Garrett and Bowers, Alex R}
}
@article {1677636,
	title = {Clustering pedestrians{\textquoteright} perceptions towards road infrastructure and traffic characteristics},
	journal = {Int J Inj Contr Saf Promot},
	volume = {30},
	number = {1},
	year = {2023},
	month = {2023 Mar},
	pages = {68-78},
	abstract = {In India, over 25,000 pedestrian fatalities occur due to road crashes every year. While several studies have identified possible causative factors that contribute to these fatalities, little is known about how pedestrians perceive their surrounding environment. This study attempts to bridge this gap by analysing the pedestrian perception of the built environment and traffic-related aspects considering urban roads (arterial and sub-arterial). Fourteen parameters were selected to assess pedestrian perception, and four factors were derived through factor analysis. The obtained factor scores were then subjected to two-step cluster analysis to determine whether pedestrian perception is different for people from different socio-economic demographics with varying travel behaviour. Based on the results obtained from the descriptive analysis, the respondents were most satisfied with the {\textquoteright}quality of streetlights at sidewalks{\textquoteright} and {\textquoteright}visibility/sight distances{\textquoteright}, while they were most dissatisfied with {\textquoteright}pedestrian volume at sidewalks{\textquoteright} and {\textquoteright}lighting facilities at crossings{\textquoteright}. From the cluster analysis, it can be summarized that female pedestrians walk less frequently than males and perceive a higher probability of collision or near-collision incidents against male pedestrians. The study findings can aid the policymakers in the assessment of the pedestrian perception of the existing road infrastructure and suggest improvements to ensure pedestrian safety.},
	keywords = {Accidents, Traffic, Built Environment, Female, Humans, Male, Pedestrians, Safety, Walking},
	issn = {1745-7319},
	doi = {10.1080/17457300.2022.2112234},
	author = {Saxena, Aditya and Yadav, Ankit Kumar}
}
@article {1789126,
	title = {Characterizing Macular Neovascularization in Myopic Macular Degeneration and Age-Related Macular Degeneration Using Swept Source OCTA},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {3855-3866},
	abstract = {PURPOSE: Visual prognosis and treatment burden for macular neovascularization (MNV) can differ between myopic macular degeneration (MMD) and age-related macular degeneration (AMD). We describe and compare MNV associated with MMD and AMD using swept-source (SS)-OCTA. PATIENTS AND METHODS: Adult patients with documented MNV associated with MMD or AMD were consecutively recruited. Qualitative and quantitative features were assessed from 6x6mm angiograms, including the MNV area and vessel density (VD). Descriptive statistics and linear regression analyses were carried out. RESULTS: Out of 75 enrolled eyes with diagnosed MNV (30 MMD-MNV and 45 AMD-MNV; mean age 55{\textpm}19 and 75{\textpm}8 years, respectively), 44 eyes had discernible MNV (11 MMD-MNV and 33 AMD-MNV) on SS-OCTA at the time of the study and were included in the analysis. The MMD-MNV group exhibited a three-fold smaller sized MNV (p=0.001), lower greatest linear dimension (p=0.009) and greatest vascular caliber (p\&lt;0.001) compared to AMD-MNVs, and had a higher prevalence of tree-in-bud pattern. Eyes with AMD showed a higher prevalence of type 1 MNVs with medusa pattern. There was no difference in the location of the MNV, shape{\textquoteright}s regularity, margins, presence of core vessel, capillary fringe, peripheral loops, or perilesional dark halo (p\&gt;0.05) between both conditions. After adjustment, decreased MNV area and increased VD were associated with the tree-in-bud pattern, whereas the diagnosis did not significantly influence those parameters. CONCLUSION: While larger studies are warranted, this study is the first to describe and compare MMD-MNV and AMD-MNV using SS-OCTA, providing relevant clinical insight on MNV secondary to MMD and AMD. These findings also further validate OCTA as a powerful tool to detect and characterize MNV non-invasively.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S440575},
	author = {Sayah, Diane N and Garg, Itika and Katz, Raviv and Zhu, Ying and Cui, Ying and Zeng, Rebecca and Tandias, Rachel and Moon, Jade Y and Vingopoulos, Filippos and Wescott, Hannah E and Baldwin, Grace and Wang, Kira and Tobias Elze and Ludwig, Cassie Ann and Vavvas, Demetrios G and Miller, Joan W and Husain, Deeba and Kim, Leo A and Patel, Nimesh A and Miller, John B}
}
@article {1364540,
	title = {Practical applications of anterior segment optical coherence tomography imaging following corneal surgery},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {125-32},
	abstract = {Anterior segment optical coherence tomography (AS-OCT) has recently emerged as an important modality for imaging of the cornea. Since its introduction less than a decade ago, it has been clinically used for the diagnosis and management of an expanding number of corneal conditions. In this review, we will discuss the applications of anterior segment optical coherence tomography after corneal surgery, focusing on penetrating and lamellar keratoplasty, keratoprosthesis, intracorneal ring segments, collagen cross-linking and refractive surgery. Anterior segment optical coherence tomography is useful in evaluating outcomes, detecting adverse events, determining prognosis, guiding management decisions, and surgical planning.},
	keywords = {Anterior Eye Segment, Cornea, Corneal Surgery, Laser, Humans, Postoperative Period, Tomography, Optical Coherence, Treatment Outcome},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.707274},
	author = {Sayegh, Rony R and Pineda, Roberto}
}
@article {1363195,
	title = {Wide-angle fundus imaging through the Boston keratoprosthesis},
	journal = {Retina},
	volume = {33},
	number = {6},
	year = {2013},
	month = {2013 Jun},
	pages = {1188-92},
	abstract = {PURPOSE: To explore the feasibility and compare the outcomes of three wide-angle fundus cameras for imaging the peripheral retina through the Type 1 Boston keratoprosthesis. METHODS: The noncontact Optos and the contact RetCam and Panoret wide-angle imaging systems were used to image the retina of eyes implanted with a keratoprosthesis. The failure-to-image rate, ease of acquisition, and quality of the images were noted, and the field of view was compared. Limitations and complications were recorded. Optos was then performed on patients referred for ultrasound B-scan evaluation, and the imaging findings were correlated. RESULTS: Retinal images with all three cameras were obtained on four eyes. Optos could be performed on all four eyes, RetCam on three, and Panoret on two. The field of view was comparable between the three different cameras. The best quality images were obtained with Optos. The external illumination of the Panoret made it impossible to image the only darkly pigmented individual in the series. Both contact devices failed to image another patient who was too agitated. Two patients had some ocular irritation from the coupling agent that resolved with replacement of the contact lens. Optos images were obtained on an additional six eyes, and findings correlated well with those on B-scan. Optos was superior to B-scan in an eye with silicone oil filling. CONCLUSION: Wide-angle fundus imaging through the keratoprosthesis is possible, and all three cameras performed similarly. The good quality of pictures obtained with the noncontact Optos, as well as its ease of use, comfort, and safety make it a preferred choice. Optos complements B-scan in the examination of the peripheral retina through the keratoprosthesis, and it may even be superior in certain settings.},
	keywords = {Aged, Aged, 80 and over, Corneal Diseases, Diagnostic Techniques, Ophthalmological, Feasibility Studies, Female, Fundus Oculi, Humans, Male, Middle Aged, Optics and Photonics, Photography, Prostheses and Implants, Visual Acuity},
	issn = {1539-2864},
	doi = {10.1097/IAE.0b013e3182869ec2},
	author = {Sayegh, Rony R and Dohlman, Claes H}
}
@article {1435415,
	title = {Using a Deep Learning Algorithm and Integrated Gradients Explanation to Assist Grading for Diabetic Retinopathy},
	journal = {Ophthalmology},
	volume = {126},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {552-564},
	abstract = {PURPOSE: To understand the impact of deep learning diabetic retinopathy (DR) algorithms on physician readers in computer-assisted settings. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: One thousand seven hundred ninety-six retinal fundus images from 1612 diabetic patients. METHODS: Ten ophthalmologists (5 general ophthalmologists, 4 retina specialists, 1 retina fellow) read images for DR severity based on the International Clinical Diabetic Retinopathy disease severity scale in each of 3 conditions: unassisted, grades only, or grades plus heatmap. Grades-only assistance comprised a histogram of DR predictions (grades) from a trained deep-learning model. For grades plus heatmap, we additionally showed explanatory heatmaps. MAIN OUTCOME MEASURES: For each experiment arm, we computed sensitivity and specificity of each reader and the algorithm for different levels of DR severity against an adjudicated reference standard. We also measured accuracy (exact 5-class level agreement and Cohen{\textquoteright}s quadratically weighted κ), reader-reported confidence (5-point Likert scale), and grading time. RESULTS: Readers graded more accurately with model assistance than without for the grades-only condition (P \&lt; 0.001). Grades plus heatmaps improved accuracy for patients with DR (P \&lt; 0.001), but reduced accuracy for patients without DR (P\&nbsp;= 0.006). Both forms of assistance increased readers{\textquoteright} sensitivity moderate-or-worse DR: unassisted: mean, 79.4\% [95\% confidence interval (CI), 72.3\%-86.5\%]; grades only: mean, 87.5\% [95\% CI, 85.1\%-89.9\%]; grades plus heatmap: mean, 88.7\% [95\% CI, 84.9\%-92.5\%] without a corresponding drop in specificity (unassisted: mean, 96.6\% [95\% CI, 95.9\%-97.4\%]; grades only: mean, 96.1\% [95\% CI, 95.5\%-96.7\%]; grades plus heatmap: mean, 95.5\% [95\% CI, 94.8\%-96.1\%]). Algorithmic assistance increased the accuracy of retina specialists above that of the unassisted reader or model alone; and increased grading confidence and grading time across all readers. For most cases, grades plus heatmap was only as effective as grades only. Over the course of the experiment, grading time decreased across all conditions, although most sharply for grades plus heatmap. CONCLUSIONS: Deep learning algorithms can improve the accuracy of, and confidence in, DR diagnosis in an assisted read setting. They also may increase grading time, although these effects may be ameliorated with experience.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.11.016},
	author = {Sayres, Rory and Taly, Ankur and Rahimy, Ehsan and Blumer, Katy and Coz, David and Hammel, Naama and Krause, Jonathan and Narayanaswamy, Arunachalam and Rastegar, Zahra and Wu, Derek and Xu, Shawn and Barb, Scott and Joseph, Anthony and Shumski, Michael and Smith, Jesse and Sood, Arjun B and Corrado, Greg S and Peng, Lily and Webster, Dale R}
}
@article {1814361,
	title = {The Incidence and Timing of Treatment-Requiring Retinopathy of Prematurity in Nanopremature and Micropremature Infants in the United States: A National Multicenter Retrospective Cohort Study},
	journal = {Ophthalmol Retina},
	volume = {8},
	number = {3},
	year = {2024},
	month = {2024 Mar},
	pages = {279-287},
	abstract = {PARTICIPANTS: This article includes 7293 infants (14 586 eyes) screened for ROP across 5 centers in the\&nbsp;United States (Austin Retina Associates, Austin, TX; Bascom Palmer Eye Institute, Miami, FL; Beaumont Eye Institute, Royal Oak, MI; Massachusetts Eye and Ear, Boston, MA; and Stanford Byers Eye Institute, Stanford, CA). PURPOSE: To analyze the incidence and timing of treatment requiring retinopathy of prematurity (ROP) in extremely small premature infants. We hypothesize that the smaller the infant by gestational age and birthweight, the higher their likelihood of requiring treatment for ROP. DESIGN: Premature infants screened for Retinopathy of Prematurity from 2002-2022 were divided into cohorts\&nbsp;based on the following criteria based on gestational age (GA) and birth weight (BW). "Micropremature infants" are infants born between 24-26 weeks GA and between 600-799 g BW. "Nanopremature infants" are born <= 24 weeks GA and <= 600 g BW. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: The incidence and timing of treatment-requiring ROP. RESULTS: We found that infants defined as nanopremature had a \~{}63\% chance of requiring treatment at an average postmenstrual age (PMA) of 36.6 weeks, whereas those defined as micropremature had a 30\% chance of requiring treatment at an average PMA of 36.3 weeks. This significantly contrasts with the risk of all screened babies for ROP where the risk of requiring treatment was 8.5\%. CONCLUSION: Micropremature and nanopremature infants are significantly more likely to require treatment for ROP. With demographic data matched to all 5 major US regions spanning the last decade, these results have the potential to inform neonatologists, pediatricians, and ophthalmologists of an important shift in the landscape of prematurity in the United States. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Birth Weight, Humans, Incidence, Infant, Infant, Newborn, Infant, Premature, Retinopathy of Prematurity, Retrospective Studies, Risk Factors, United States},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.10.003},
	author = {Scarboro, Shannon D and Harper, Clio Armitage and Karsaliya, Gopal and Ghoraba, Hashem and Moshfeghi, Darius M and Al-Khersan, Hasenin and Robles-Holmes, Hailey Kay and Fan, Kenneth C and Berrocal, Audina M and Hoyek, Sandra and Patel, Nimesh A and Sbrocca, Rocco and Capone, Antonio and Drenser, Kimberly A and Wood, Edward H}
}
@article {369051,
	title = {In vivo biomechanical mapping of normal and keratoconus corneas.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {4},
	year = {2015},
	month = {2015 Apr 1},
	pages = {480-2},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.5641},
	author = {Scarcelli, Giuliano and Besner, Sebastien and Pineda, Roberto and Kalout, Patricia and Yun, Seok Hyun}
}
@article {1351184,
	title = {Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {7},
	year = {2014},
	month = {2014 Jun 17},
	pages = {4490-5},
	abstract = {PURPOSE: Loss of corneal strength is a central feature of keratoconus progression. However, it is currently difficult to measure corneal mechanical changes noninvasively. The objective of this study is to evaluate if Brillouin optical microscopy can differentiate the mechanical properties of keratoconic corneas versus healthy corneas ex vivo. METHODS: We obtained eight tissue samples from healthy donor corneas used in Descemet{\textquoteright}s stripping endothelial keratoplasty (DSEK) and 10 advanced keratoconic corneas from patients undergoing deep anterior lamellar keratoplasty (DALK). Within 2 hours after surgery, a confocal Brillouin microscope using a monochromatic laser at 532 nm was used to map the Brillouin frequency shifts of the corneas. RESULTS: The mean Brillouin shift in the anterior 200 μm of the keratoconic corneas at the cone was measured to be 7.99 {\textpm} 0.10 GHz, significantly lower than 8.17 {\textpm} 0.06 GHz of the healthy corneas (P \&lt; 0.001). The Brillouin shift in the keratoconic corneas decreased with depth from the anterior toward posterior regions with a steeper slope than in the healthy corneas (P \&lt; 0.001). Within keratoconic corneas, the Brillouin shift in regions away from the apex of the cone was significantly higher than within the cone region (P \&lt; 0.001). CONCLUSIONS: Brillouin measurements revealed notable differences between healthy and keratoconic corneas. Importantly, Brillouin imaging showed that the mechanical loss is primarily concentrated within the area of the keratoconic cone. Outside the cone, the Brillouin shift was comparable with that of healthy corneas. The results demonstrate the potential of Brillouin microscopy for diagnosis and treatment monitoring of keratoconus.},
	keywords = {Adult, Biomechanical Phenomena, Cornea, Corneal Transplantation, Descemet Stripping Endothelial Keratoplasty, Disease Progression, Elastic Modulus, Elasticity Imaging Techniques, Female, Healthy Volunteers, Humans, Imaging, Three-Dimensional, Keratoconus, Male, Microscopy, Confocal, Middle Aged},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-14450},
	author = {Scarcelli, Giuliano and Besner, Sebastien and Pineda, Roberto and Yun, Seok Hyun}
}
@article {1586164,
	title = {Neurotrophic Keratopathy in Pediatric Patients},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {289-295},
	abstract = {Purpose: This review provides an overview of the causes and treatment of neurotrophic keratopathy in the pediatric population.Methods: A thorough review of the current literature discussing neurotrophic keratopathy was conducted then summarized.Results:Fourty-nine papers were reviewed. Congenital and acquired causes of neurotrophic keratopathy exist in the pediatric population. Both medical and surgical approaches to treatment have been trialed, albeit to a\&nbsp;limited extent, in pediatric patients. Conservative treatment includes topical lubrication and antibiotics to prevent concurrent infectious ulcer formation. Various neurotrophic factors have been trialed in the form of serum drops to restore corneal sensation when conservative measures fail. Surgically, different corneal neurotization techniques have been developed whereby a donor nerve is routed to the anesthetized cornea to restore innervation and sensation. Conclusions: Advances in the treatment of neurotrophic keratopathy have made corneal reinnervation and restoration of vision more easily attainable in pediatric patients.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1896747},
	author = {Scelfo, C and Mantagos, I S}
}
@article {1586175,
	title = {Effect of inferior oblique myectomy on primary position when combined with lateral rectus recession for intermittent exotropia},
	journal = {Eur J Ophthalmol},
	volume = {32},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {559-562},
	abstract = {PURPOSE: To evaluate the surgical success and need for adjustment due to overcorrection in patients who undergo inferior oblique myectomy (IOM) combined with lateral rectus recession (LRc) for intermittent exotropia in the setting of inferior oblique overaction. METHODS: A retrospective chart review was conducted of patients with intermittent exotropia who underwent LRc using adjustable sutures alone versus LRc combined with IOM between January 2010 and July 2018 at our institution. Binocular alignment was recorded before and within one week of surgery. Evaluation measures noted were surgical success (defined as distance alignment of ⩽10 prism diopters) and need for postoperative adjustment due to overcorrection. RESULTS: Of 48 patients, 24 underwent LRc alone and 24 underwent LRc combined with IOM; all 48 patients had adjustable sutures. Surgical success was significantly higher in the LRc alone group (91.6\%) compared with the LRc with IOM group (62.5\%) (p = 0.036). The need for postoperative adjustment due to overcorrection was also significantly higher in the LRc with IOM group (20.8\%) compared with the LRc alone group (0\%) (p = 0.049). CONCLUSIONS: In this study, more patients needed adjustment for overcorrection after undergoing LRc combined with IOM versus LRc alone. Since the tertiary action of the inferior oblique is abduction it is possible that, in patients with inferior oblique overaction, surgically weakening the inferior oblique causes more esodeviation and overcorrection. Thus, surgical correction of exotropia and inferior oblique overaction using LRc combined with IOM may lead to overcorrection and increased need for postoperative adjustment.},
	keywords = {Exotropia, Follow-Up Studies, Humans, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Retrospective Studies, Strabismus, Treatment Outcome, Vision, Binocular},
	issn = {1724-6016},
	doi = {10.1177/11206721211002706},
	author = {Scelfo, Christina and Elhusseiny, Abdelrahman M and Alkharashi, Maan}
}
@article {1632307,
	title = {Ocular Surface Disease in Glaucoma Patients},
	journal = {Curr Eye Res},
	volume = {48},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {219-230},
	abstract = {PURPOSE: To review the most recent studies in the literature regarding the ocular surface in glaucoma patients and treatment options aimed to reduce ocular surface disease in this population. METHODS: We performed a literature search in the electronic databases of PubMed CENT RAL, Google Scholar, EMBASE the Register of Controlled Trials, and Ovid MEDLINE using the following terms: "ocular surface", "dry eye", "glaucoma", "selective laser trabeculoplasty", "glaucoma surgery", "preservatives", "preservative free", "ocular surface disease index", "tear break up time", "MMP-9" and "conjunctival hyperemia". RESULTS: Over the last several years, several studies have demonstrated the changes to the ocular surface in the setting of glaucoma, the best tests for markers of dry eye, and how management can be altered to help address ocular surface disease routinely or in preparation for glaucoma surgery. CONCLUSION: Ocular surface disease in the glaucoma patient population is widely recognized. It should be addressed to maximize patient compliance and quality of life.},
	keywords = {Antihypertensive Agents, Dry Eye Syndromes, Glaucoma, Humans, Intraocular Pressure, Ophthalmic Solutions, Preservatives, Pharmaceutical, Quality of Life},
	issn = {1460-2202},
	doi = {10.1080/02713683.2022.2041041},
	author = {Scelfo, Christina and ElSheikh, Reem H and Shamim, Muhammad M and Abbasian, Javaneh and Ghaffarieh, Alireza and Elhusseiny, Abdelrahman M}
}
@article {1363196,
	title = {Patient reported differences in dry eye disease between men and women: impact, management, and patient satisfaction},
	journal = {PLoS One},
	volume = {8},
	number = {9},
	year = {2013},
	month = {2013},
	pages = {e76121},
	abstract = {PURPOSE: Dry eye disease affects women twice as often as men, but there is little information on whether dry eye treatments, treatment satisfaction, or the impact of dry eye disease on patients{\textquoteright} lives and vision might differ by sex. DESIGN: Questionnaire survey of 4000 participants in the Women{\textquoteright}s Health Study and the Physicians{\textquoteright} Health Studies I and II with a prior report of a diagnosis of DED. METHODS: Among participants who re-confirmed a diagnosis of dry eye disease, we assessed symptoms, treatments, patient satisfaction and impact of dry eye disease, and analyzed differences between men and women using regression models. RESULTS: The final study population consisted of 1,518 women (mean age 70.7 years) and 581 men (mean age 76.7 years), with a mean reported duration of dry eye disease of 10.5 years and 10.1 years, respectively. The frequency and severity of dry eye disease symptoms were higher among women (each P\&lt;0.0001), and women reported a greater impact on everyday activities (P\&lt;0.0001). Women were more likely to use artificial tears (P\&lt;0.0001) use them more often (P\&lt;0.0001), and to use Restasis{\textregistered} (P\&lt;0.0001), omega-3 fatty acids (P=0.0006), and have punctal occlusion (P=0.005). Women spent more money per month on dry eye treatments (P\&lt;0.0001), but reported greater dissatisfaction with treatment side effects (P=0.001), and the amount of time before treatments started working (P=0.03). CONCLUSIONS: These data show that dry eye disease is generally experienced as being more severe among women, having a greater impact on their self-assessed well-being.},
	keywords = {Aged, Dry Eye Syndromes, Female, Humans, Male, Odds Ratio, Patient Satisfaction, Regression Analysis, Sex Factors, Surveys and Questionnaires, Treatment Outcome, United States},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0076121},
	author = {Schaumberg, Debra A and Uchino, Miki and Christen, William G and Semba, Richard D and Buring, Julie E and Li, Jim Z}
}
@article {1351185,
	title = {Prospective study of common variants in CX3CR1 and risk of macular degeneration: pooled analysis from 5 long-term studies},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {84-95},
	abstract = {IMPORTANCE: The CX3CR1 gene is implicated as a candidate gene for age-related macular degeneration (AMD) through several lines of evidence. There is uncertainty, however, as to whether common genetic variants in CX3CR1 alter risk of AMD, since prior studies have been inconsistent and mostly limited to evaluation of 2 nonsynonymous variants, T280M (rs3732378) and V249I (rs3732379). OBJECTIVE: To determine if common variants in CX3CR1 predict future risk of AMD. DESIGN, SETTING, AND PARTICIPANTS: Prospective nested case-control study within 5 large study populations with long-term follow-up. We measured genotypes for T280M, V249I, and 13 other common single-nucleotide polymorphisms (SNPs) of the CX3CR1 gene among people who developed AMD (n = 1110, including 369 with neovascular AMD) and 2532 age- and sex-matched controls. MAIN OUTCOMES AND MEASURES: We determined the incidence rate ratios (RR) and 95\% CIs for incidence of AMD for each variant and examined interactions with other AMD-associated variants and modifiable risk factors. RESULTS: In additive genetic models, we identified nonsignificant associations with AMD for T280M (RR, 0.87; P = .07) and 3 other SNPs, rs2853707 (RR, 0.88; P = .07), rs12636547 (RR, 0.85; P = .10), and rs1877563 (RR, 0.84; P = .06), 1 of which, rs2853707, is positioned in the CX3CR1 promoter region and was associated with neovascular AMD (RR, 0.75; P = .03). We observed that a recessive model was a better fit to the data for some SNPs, with associations between rs11715522 and AMD (RR, 1.27; P = .03) and between rs2669845 (RR, 3.10; P = .04), rs2853707 (RR, 0.48; P = .050), and rs9868689 (RR, 0.31; P = .02) and neovascular AMD. Moreover, in exploratory analyses, we identified a number of possible interactions including between V249I and rs2669845 and dietary intake of ω-3 fatty acids (P = .004 and P = .009, respectively) for AMD; between rs2669845 and obesity (P = .03) for neovascular AMD; between T280M and complement component 3 (C3) R102G for AMD (P = .03); between rs2669845 and Y402H in complement factor H for AMD (P = .04); and between rs2669845, rs2853707, and V249I and C3 R102G for neovascular AMD (P = .008; .04; and .002, respectively). CONCLUSIONS AND RELEVANCE: This study failed to identify significant associations between common CX3CR1 variants and AMD after considering the number of SNPs analyzed and multiple comparisons. However, we observed evidence consistent with recessive modes of association and that an effect of CX3CR1 variants may depend on other factors including dietary intake of ω-3 fatty acids, obesity, and genotypes at CFH Y402H and C3 R102G. If replicated in other populations, these findings would support a role for CX3CR1 in AMD but also suggest that its role may involve mechanisms that are independent of the T280M/V249I variations.},
	keywords = {Alleles, Case-Control Studies, Chromosomes, Human, Pair 3, Complement C3, Complement Factor H, CX3C Chemokine Receptor 1, Dietary Fats, Unsaturated, Double-Blind Method, Fatty Acids, Omega-3, Female, Follow-Up Studies, Gene-Environment Interaction, Genotype, Health Personnel, Humans, Incidence, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Proteins, Receptors, Chemokine, Risk Factors, Wet Macular Degeneration},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.5506},
	author = {Schaumberg, Debra A and Rose, Lynda and Deangelis, Margaret M and Semba, Richard D and Hageman, Gregory S and Chasman, Daniel I}
}
@article {1732516,
	title = {Microbial patterns and culture utility in orbital cellulitis},
	journal = {J AAPOS},
	year = {2023},
	month = {2023 Jul 22},
	abstract = {PURPOSE: To determine the prevalence and types of pathogens found in children with orbital cellulitis and to evaluate the utility of nonoperative cultures. METHODS: This was a retrospective cohort study of children with imaging-confirmed orbital cellulitis over a period of 8 years. Outcomes included prevalence and types of organisms, polymicrobial infection, mixed aerobic-anaerobic infection, effect of age, and culture utility. RESULTS: Of 220 children with orbital cellulitis, 112 (51\%) had cultures taken; 69 (31\%) had surgical intervention. Culture sources for the 112 children with cultures included blood (57 patients [51\%]), sinus (53 [47\%]), orbit (42 [38\%]), brain (6 [5\%]), and skin/conjunctiva/lacrimal sac (6 [5\%]). Streptococcus anginosus group strains grew in cultures from 19 children (17\%); methicillin-sensitive Staphylococcus aureus (MSSA), in 15 (13\%); Streptococcus pyogenes, in 12 (11\%); methicillin-resistant Staphylococcus aureus (MRSA), in 6 (5\%); anaerobic/facultative gram negative rods, in 8 (7\%); anaerobic Gram-positive cocci, other Viridans group streptococci, and Streptococci pneumoniae, in 3 (3\%) each; and normal respiratory/skin flora, in 23 (21\%). Polymicrobial infection (P = 0.08) and anaerobic organisms (P = 0.58) did not differ by age (range, 0.1-16.8 years). In all 220 (100\%) children, nonoperative cultures were either not obtained (108 [49\%]), not helpful in avoiding surgery (69 [31\%]), showed no growth (39 [18\%]), or grew an organism that did not change management from empiric therapy (4 [2\%]). CONCLUSIONS: While many organisms may be cultured from children with orbital cellulitis, Streptococcus and MSSA were the most common in our study cohort. MRSA is uncommon, so initial empiric coverage is not necessary. Rates of polymicrobial and anaerobic infection were similar across ages. Our results indicate that nonoperative cultures are not indicated in the initial medical management of orbital cellulitis; in our cohort, they neither resulted in treatment changes nor helped avoid surgery.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.05.010},
	author = {Schein, Yvette and Lin, Lisa Y and Revere, Karen and Russo, Michael E and Yu, Yinxi and Ying, Gui-Shuang and Binenbaum, Gil}
}
@article {1474206,
	title = {Spatiotemporal changes in the human lens proteome: Critical insights into long-lived proteins},
	journal = {Prog Retin Eye Res},
	year = {2019},
	month = {2019 Nov 06},
	pages = {100802},
	abstract = {The ocular lens is a unique tissue that contains an age gradient of cells and proteins ranging from newly differentiated cells containing newly synthesized proteins to cells and proteins that are as old as the organism. Thus, the ocular lens is an excellent model for studying long-lived proteins (LLPs) and the effects of aging and post-translational modifications on protein structure and function. Given the architecture of the lens, with young fiber cells in the outer cortex and the oldest cells in the lens nucleus, spatially-resolved studies provide information on age-specific protein changes. In this review, experimental strategies and proteomic methods that have been used to examine age-related and cataract-specific changes to the human lens proteome are described. Measured spatio-temporal changes in the human lens proteome are summarized and reveal a highly consistent, time-dependent set of modifications observed in transparent human lenses. Such measurements have led to the discovery of cataract-specific modifications and the realization that many animal systems are unsuitable to study many of these modifications. Mechanisms of protein modifications such as deamidation, racemization, truncation, and protein-protein crosslinking are presented and the implications of such mechanisms for other long-lived proteins in other tissues are discussed in the context of age-related neurological diseases. A comprehensive understanding of LLP modifications will enhance our ability to develop new therapies for the delay, prevention or reversal of age-related diseases.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2019.100802},
	author = {Schey, Kevin L and Wang, Zhen and Friedrich, Michael G and Garland, Donita L and Truscott, Roger J W}
}
@article {1460360,
	title = {Axis of rotation as a basic feature in visual search},
	journal = {Atten Percept Psychophys},
	year = {2019},
	month = {2019 Aug 19},
	abstract = {Searching for a "Q" among "O"s is easier than the opposite search (Treisman \&amp; Gormican in Psychological Review, 95, 15-48, 1988). In many cases, such "search asymmetries" occur because it is easier to search when a target is defined by the presence of a feature (i.e., the line terminator defining the tail of the "Q"), rather than by its absence. Treisman proposed that features that produce a search asymmetry are "basic" features in visual search (Treisman \&amp; Gormican in Psychological Review, 95, 15-48, 1988; Treisman \&amp; Souther in Journal of Experimental Psychology: General, 114, 285-310, 1985). Other stimulus attributes, such as color, orientation, and motion, have been found to produce search asymmetries (Dick, Ullman, \&amp; Sagi in Science, 237, 400-402, 1987; Treisman \&amp; Gormican in Psychological Review, 95, 15-48, 1988; Treisman \&amp; Souther in Journal of Experimental Psychology: General, 114, 285-310, 1985). Other stimulus properties, such as facial expression, produce asymmetries because one type of item (e.g., neutral faces) demands less attention in search than another (e.g., angry faces). In the present series of experiments, search for a rolling target among spinning distractors proved to be more efficient than searching for a spinning target among rolling distractors. The effect does not appear to be due to differences in physical plausibility, direction of motion, or texture movement. Our results suggest that the spinning stimuli demand less attention, making search through spinning distractors for a rolling target easier than the opposite search.},
	issn = {1943-393X},
	doi = {10.3758/s13414-019-01834-0},
	author = {Schill, Hayden M and Cain, Matthew S and Josephs, Emilie L and Wolfe, Jeremy M}
}
@article {1589760,
	title = {Relationships between expertise and distinctiveness: Abnormal medical images lead to enhanced memory performance only in experts},
	journal = {Mem Cognit},
	volume = {49},
	number = {6},
	year = {2021},
	month = {2021 Aug},
	pages = {1067-1081},
	abstract = {Memories are encoded in a manner that depends on our knowledge and expectations ("schemas"). Consistent with this, expertise tends to improve memory: Experts have elaborated schemas in their domains of expertise, allowing them to efficiently represent information in this domain (e.g., chess experts have enhanced memory for realistic chess layouts). On the other hand, in most situations, people tend to remember abnormal or surprising items best-those that are also rare or out-of-the-ordinary occurrences (e.g., surprising-but not random-chess board configurations). This occurs, in part, because such images are distinctive relative to other images. In the current work, we ask how these factors interact in a particularly interesting case-the domain of radiology, where experts actively search for abnormalities. Abnormality in mammograms is typically focal but can be perceived in the global "gist" of the image. We ask whether, relative to novices, expert radiologists show improved memory for mammograms. We also test for any additional advantage for abnormal mammograms that can be thought of as unexpected or rare stimuli in screening. We find that experts have enhanced memory for focally abnormal images relative to normal images. However, radiologists showed no memory benefit for images of the breast that were not focally abnormal, but were only abnormal in their gist. Our results speak to the role of schemas and abnormality in expertise; the necessity for spatially localized abnormalities versus abnormalities in the gist in enhancing memory; and the nature of memory and decision-making in radiologists.},
	issn = {1532-5946},
	doi = {10.3758/s13421-021-01160-7},
	author = {Schill, Hayden M and Wolfe, Jeremy M and Brady, Timothy F}
}
@article {1364541,
	title = {Telomerase immortalization of human corneal endothelial cells yields functional hexagonal monolayers},
	journal = {PLoS One},
	volume = {7},
	number = {12},
	year = {2012},
	month = {2012},
	pages = {e51427},
	abstract = {Human corneal endothelial cells (HCEnCs) form a monolayer of hexagonal cells whose main function is to maintain corneal clarity by regulating corneal hydration. HCEnCs are derived from neural crest and are arrested in the post-mitotic state. Thus cell loss due to aging or corneal endothelial disorders leads to corneal edema and blindness-the leading indication for corneal transplantation. Here we show the existence of morphologically distinct subpopulations of HCEnCs that are interspersed among primary cells and exhibit enhanced self-renewal competence and lack of phenotypic signs of cellular senescence. Colonies of these uniform and hexagonal HCEnCs (HCEnC-21) were selectively isolated and demonstrated high proliferative potential that was dependent on endogenous upregulation of telomerase and cyclin D/CDK4. Further transduction of HCEnC-21 with telomerase yielded a highly proliferative corneal endothelial cell line (HCEnT-21T) that was devoid of oncogenic transformation and retained critical corneal endothelial cell characteristics and functionality. This study will significantly impact the fields of corneal cell biology and regenerative medicine.},
	keywords = {Biomarkers, Cell Differentiation, Cell Line, Cell Proliferation, Cell Shape, Cellular Senescence, Cyclin D, Cyclin-Dependent Kinase 4, Endothelium, Corneal, Humans, Ion Pumps, Ion Transport, Telomerase, Transduction, Genetic, Tumor Suppressor Protein p53},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0051427},
	author = {Schmedt, Thore and Chen, Yuming and Nguyen, Tracy T and Li, Shimin and Bonanno, Joseph A and Jurkunas, Ula V}
}
@article {1363197,
	title = {Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients},
	journal = {Retina},
	volume = {33},
	number = {9},
	year = {2013},
	month = {2013 Oct},
	pages = {1791-9},
	abstract = {PURPOSE: To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. METHODS: Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. RESULTS: Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. CONCLUSION: The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications.},
	keywords = {Aged, Aged, 80 and over, Antiviral Agents, Aqueous Humor, CD4 Lymphocyte Count, Chronic Disease, Cytomegalovirus, Cytomegalovirus Retinitis, DNA, Viral, Drug Therapy, Combination, Female, Foscarnet, Ganciclovir, HIV Seronegativity, Humans, Male, Middle Aged, Necrosis, Polymerase Chain Reaction, Retinal Neovascularization, Retinal Vasculitis, Retinal Vessels, Retrospective Studies, Uveitis, Posterior, Vitreous Body},
	issn = {1539-2864},
	doi = {10.1097/IAE.0b013e318285f486},
	author = {Schneider, Eric W and Elner, Susan G and van Kuijk, Frederik J and Goldberg, Naomi and Lieberman, Ronni M and Eliott, Dean and Johnson, Mark W}
}
@article {1363198,
	title = {The hermansky-pudlak syndrome: clinical features and imperatives from an ophthalmic perspective},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {387-91},
	abstract = {The Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive condition comprising nine genetically heterogeneous entities that feature oculocutaneous albinism (OCA) and bleeding tendency as their principal clinical manifestations. The pathogenesis of HPS involves disturbances in the biogenesis and trafficking of lysosome-related organelles. While the ophthalmologist is trained to address the ocular manifestations of OCA, it is critical for the provider to consider HPS when examining OCA patients as its systemic sequelae may be associated with morbidity and mortality. If there is suspicion of HPS in a patient with albinism, the ophthalmologist should enlist the aid of consultants to confirm the diagnosis and monitor for systemic features. As the nine HPS subtypes explored in this article vary widely in the character and severity of their associated systemic manifestations, some authors advocate determining the specific gene defect in each HPS patient in order to optimize care and provide anticipatory guidance.},
	keywords = {Blood Coagulation Disorders, Inherited, Hermanski-Pudlak Syndrome, Humans},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825280},
	author = {Schneier, Andrew J and Fulton, Anne B}
}
@article {1664948,
	title = {The importance of contrast features in rat vision},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Jan 10},
	pages = {459},
	abstract = {Models of object recognition have mostly focused upon the hierarchical processing of objects from local edges up to more complex shape features. An alternative strategy that might be involved in pattern recognition centres around coarse-level contrast features. In humans and monkeys, the use of such features is most documented in the domain of face perception. Given prior suggestions that, generally, rodents might rely upon contrast features for object recognition, we hypothesized that they would pick up the typical contrast features relevant for face detection. We trained rats in a face-nonface categorization task with stimuli previously used in computer vision and tested for generalization with new, unseen stimuli by including manipulations of the presence and strength of a range of contrast features previously identified to be relevant for face detection. Although overall generalization performance was low, it was significantly modulated by contrast features. A model taking into account the summed strength of contrast features predicted the variation in accuracy across stimuli. Finally, with deep neural networks, we further investigated and quantified the performance and representations of the animals. The findings suggest that rat behaviour in visual pattern recognition tasks is partially explained by contrast feature processing.},
	keywords = {Animals, Facial Recognition, Humans, Neural Networks, Computer, Pattern Recognition, Visual, Photic Stimulation, Rats, Vision, Ocular, Visual Perception},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-27533-3},
	author = {Schnell, Anna Elisabeth and Vinken, Kasper and Op de Beeck, Hans}
}
@article {1589745,
	title = {Notch3 Signaling and Aggregation as Targets for the Treatment of CADASIL and Other NOTCH3-Associated Small-Vessel Diseases},
	journal = {Am J Pathol},
	volume = {191},
	number = {11},
	year = {2021},
	month = {2021 11},
	pages = {1856-1870},
	abstract = {Mutations in the NOTCH3 gene can lead to small-vessel disease in humans, including the well-characterized cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a condition caused by NOTCH3 mutations altering the number of cysteine residues in the extracellular domain of Notch3. Growing evidence indicates that other types of mutations in NOTCH3, including cysteine-sparing missense mutations or frameshift and premature stop codons, can lead to small-vessel disease phenotypes of variable severity or penetrance. There are currently no disease-modifying therapies for small-vessel disease, including those associated with NOTCH3 mutations. A deeper understanding of underlying molecular mechanisms and clearly defined targets are needed to promote the development of therapies. This review discusses two key pathophysiological mechanisms believed to contribute to the emergence and progression of small-vessel disease associated with NOTCH3 mutations: abnormal Notch3 aggregation and aberrant Notch3 signaling. This review offers a summary of the literature supporting and challenging the relevance of these mechanisms, together with an overview of available preclinical experiments derived from these mechanisms. It highlights knowledge gaps and future research directions. In view of recent evidence demonstrating the relatively high frequency of NOTCH3 mutations in the population, and their potential role in promoting small-vessel disease, progress in the development of therapies for NOTCH3-associated small-vessel disease is urgently needed.},
	keywords = {Animals, CADASIL, Cerebral Small Vessel Diseases, Humans, Mutation, Protein Aggregation, Pathological, Receptor, Notch3, Signal Transduction},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.03.015},
	author = {Schoemaker, Dorothee and Arboleda-Velasquez, Joseph F}
}
@article {1417576,
	title = {Clinical and research applications of magnetic resonance imaging in the study of CADASIL},
	journal = {Neurosci Lett},
	volume = {698},
	year = {2019},
	month = {2019 Apr 17},
	pages = {173-179},
	abstract = {Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited small vessel disease that leads to early cerebrovascular events and functional disability. It is the most common single-gene disorder leading to stroke. Magnetic resonance imaging (MRI) is a central component of the diagnosis and monitoring of CADASIL. Here we provide a descriptive review of the literature on three important aspects pertaining to the use of MRI in CADASIL. First, we review past research exploring MRI markers for this disease. Secondly, we describe results from studies investigating associations between neuroimaging abnormalities and neuropathology in CADASIL. Finally, we discuss previous findings relating MRI markers to clinical symptoms. This review thus provides a summary of the current state of knowledge regarding the use of MRI in CADASIL as well as suggestions for future research.},
	issn = {1872-7972},
	doi = {10.1016/j.neulet.2019.01.014},
	author = {Schoemaker, Dorothee and Quiroz, Yakeel T and Torrico-Teave, Heirangi and Arboleda-Velasquez, Joseph F}
}
@article {1517195,
	title = {The INECO Frontal Screening for the Evaluation of Executive Dysfunction in Cerebral Small Vessel Disease: Evidence from Quantitative MRI in a CADASIL Cohort from Colombia},
	journal = {J Int Neuropsychol Soc},
	volume = {26},
	number = {10},
	year = {2020},
	month = {2020 Nov},
	pages = {1006-1018},
	abstract = {OBJECTIVES: Executive dysfunction is a predominant cognitive symptom in cerebral small vessel disease (SVD). The Institute of Cognitive Neurology Frontal Screening (IFS) is a well-validated screening tool allowing the rapid assessment of multiple components of executive function in Spanish-speaking individuals. In this study, we examined performance on the IFS in subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited condition leading to the early onset of SVD. We further explored associations between performance on the IFS and magnetic resonance imaging (MRI) markers of SVD. METHODS: We recruited 24 asymptomatic CADASIL subjects and 23 noncarriers from Colombia. All subjects underwent a research MRI and a neuropsychological evaluation, including the IFS. Structural MRI markers of SVD were quantified in each subject, together with an SVD Sum Score representing the overall burden of cerebrovascular alterations. General linear model, correlation, and receiver operating characteristic curve analyses were used to explore group differences on the IFS and relationships with MRI markers of SVD. RESULTS: CADASIL subjects had a significantly reduced performance on the IFS Total Score. Performance on the IFS correlated with all quantified markers of SVD, except for brain atrophy and perivascular spaces enlargement. Finally, while the IFS Total Score was not able to accurately discriminate between carriers and noncarriers, it showed adequate sensitivity and specificity in detecting the presence of multiple MRI markers of SVD. CONCLUSIONS: These results suggest that the IFS may be a useful screening tool to assess executive function and disease severity in the context of SVD.},
	issn = {1469-7661},
	doi = {10.1017/S1355617720000533},
	author = {Schoemaker, Dorothee and Zuluaga, Yesica and Viswanathan, Anand and Shrimer, Markus and Torrico-Teave, Heirangi and Velilla, Lina and Ospina, Carolina and Ospina, Gloria Garcia and Lopera, Francisco and Arboleda-Velasquez, Joseph F and Quiroz, Yakeel T}
}
@article {1598046,
	title = {Global Cardiovascular Risk Profile and Cerebrovascular Abnormalities in Presymptomatic Individuals with CADASIL or Autosomal Dominant Alzheimer{\textquoteright}s Disease},
	journal = {J Alzheimers Dis},
	year = {2021},
	month = {2021 Jun 03},
	abstract = {BACKGROUND: Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer{\textquoteright}s disease and vascular dementia. OBJECTIVE: Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer{\textquoteright}s disease and vascular dementia. METHODS: We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer{\textquoteright}s disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score. RESULTS: In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (B = -0.06, p \&lt;  0.05) and an increased severity of cerebral microbleeds (B = 0.13, p \&lt;  0.001), lacunes (B = 0.30, p \&lt;  0.001), and perivascular space enlargement in the basal ganglia (B = 0.50, p \&lt;  0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (B = 0.06, p \&lt;  0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD. CONCLUSION: Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks.},
	issn = {1875-8908},
	doi = {10.3233/JAD-210313},
	author = {Schoemaker, Dorothee and Velilla, Lina and Zuluaga, Yesica and Baena, Ana and Ospina, Carolina and Bocanegra, Yamile and Alvarez, Sergio and Ochoa-Escudero, Martin and Guzm{\'a}n-V{\'e}lez, Edmarie and Martinez, Jairo and Lopera, Francisco and Arboleda-Velasquez, Joseph F and Quiroz, Yakeel T}
}
@article {1363199,
	title = {Cellular and subbasal nerve alterations in early stage Fuchs{\textquoteright} endothelial corneal dystrophy: an in vivo confocal microscopy study},
	journal = {Eye (Lond)},
	volume = {27},
	number = {1},
	year = {2013},
	month = {2013 Jan},
	pages = {42-9},
	abstract = {PURPOSE: To analyze the morphology and density of corneal epithelial cells, keratocytes, and subbasal nerves, in patients with early stage Fuchs{\textquoteright} endothelial corneal dystrophy (FECD) by in vivo confocal microscopy (IVCM).

METHODS: IVCM (Confoscan 4, Nidek, Inc.) of the central cornea was performed in 30 corneas of 30 patients with early stage FECD and 13 corneas of 13 normal controls. Images were analyzed for morphology and density of the superficial and basal epithelial cells, keratocyte density, endothelial cell density (ECD), as well as subbasal corneal nerve parameters. Central corneal thickness (CCT) was measured in all patients and normals by ultrasound pachymetry.

RESULTS: The ECD was significantly lower (-45.5\%, P,
	keywords = {Aged, Aged, 80 and over, Cornea, Corneal Keratocytes, Corneal Pachymetry, Cross-Sectional Studies, Endothelium, Corneal, Epithelium, Corneal, Female, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Male, Microscopy, Confocal, Middle Aged, Ophthalmic Nerve, Retrospective Studies, Ultrasonography},
	issn = {1476-5454},
	doi = {10.1038/eye.2012.220},
	author = {Schrems-Hoesl, L M and Schrems, W A and Cruzat, A and Shahatit, B M and Bayhan, H A and Jurkunas, U V and Hamrah, P}
}
@article {1632281,
	title = {Imaging diabetic retinal disease: clinical imaging requirements},
	journal = {Acta Ophthalmol},
	volume = {100},
	number = {7},
	year = {2022},
	month = {2022 Nov},
	pages = {752-762},
	abstract = {Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus (DM) and it contributes substantially to the burden of disease globally. During the last decades, the development of multiple imaging modalities to evaluate DR, combined with emerging treatment possibilities, has led to the implementation of large-scale screening programmes resulting in improved prevention of vision loss. However, not all patients are able to participate in such programmes and not all are at equal risk of DR development and progression. In this review, we discuss the relevance of the currently available imaging modalities for the evaluation of DR: colour fundus photography (CFP), ultrawide-field photography (UWFP), fundus fluorescein angiography (FFA), optical coherence tomography (OCT), OCT angiography (OCTA) and functional testing. Furthermore, we suggest where a particular imaging technique of DR may aid the evaluation of the disease in different clinical settings. Combining information from various imaging modalities may enable the design of more personalized care including the initiation of treatment and understanding the progression of disease more adequately.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Diagnostic Techniques, Ophthalmological, Fluorescein Angiography, Humans, Photography, Retinal Vessels, Tomography, Optical Coherence},
	issn = {1755-3768},
	doi = {10.1111/aos.15110},
	author = {Schreur, Vivian and Larsen, Morten B and Sobrin, Lucia and Bhavsar, Abdhish R and den Hollander, Anneke I and Klevering, B Jeroen and Hoyng, Carel B and de Jong, Eiko K and Grauslund, Jakob and Peto, Tunde}
}
@article {303856,
	title = {Consensus statement on the immunohistochemical detection of ocular lymphatic vessels.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {10},
	year = {2014},
	month = {2014},
	pages = {6440-2},
	abstract = {There is currently considerable controversy about existence and classification of "lymphatic vessels" in the eye. Some of the confusion is certainly caused by inappropriate use (or nonuse) of the correct immunohistochemical markers. Many experts in the field expressed the need for a consensus statement, and, in this perspective, authors offer arguments and solutions to reliably continue with immunohistochemical ocular lymphatic research.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15638},
	author = {Schroedl, Falk and Kaser-Eichberger, Alexandra and Schlereth, Simona L and Bock, Felix and Regenfuss, Birgit and Reitsamer, Herbert A and Lutty, Gerard A and Maruyama, Kazuichi and Chen, Lu and L{\"u}tjen-Drecoll, Elke and Dana, Reza and Kerjaschki, Dontscho and Alitalo, Kari and De Stefano, Maria Egle and Junghans, Barbara M and Heindl, Ludwig M and Cursiefen, Claus}
}
@article {1043261,
	title = {Quantifying Fundus Autofluorescence in Patients With Retinitis Pigmentosa},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {3},
	year = {2017},
	month = {2017 Mar 01},
	pages = {1843-1855},
	abstract = {Purpose: Using quantitative fundus autofluorescence (qAF), we analyzed short-wavelength autofluorescent (SW-AF) rings in RP. Methods: Short-wavelength autofluorescent images (486 nm excitation) of 40 patients with RP (69 eyes) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF was measured in eight preset segments (qAF8) and in region of interest (ROI)-qAF (200-700 μm) within and external to the borders of the rings at superior, temporal, and inferior sites relative to the ring. For both groups, qAF in patients with RP was compared to age-similar and race/ethnicity-matched healthy eyes at equivalent retinal locations. Results: In 71\% of eyes of RP patients, qAF8 acquired internal to the inner border of the ring, was within the 95\% confidence interval (CI) for healthy eyes, while in the remaining RP eyes qAF8 was either higher or lower than the CI. Measured external to the ring, qAF8 values were within the CI in 47\% of RP eyes with the other eyes being higher or lower. In 28\% of sites measured by ROI-qAF within the SW-AF ring, values were above the 95\% CI of healthy controls. Region of interest-qAF measured just external to the ring was within the CI of healthy eyes in 74\% of locations. The average local elevation in qAF within the ring was approximately 15\%. In SD-OCT scans, photoreceptor-attributable reflectivity bands were thinned within and external to the ring. Conclusions: Increased fluorophore production may be a factor in the formation of the SW-AF rings in RP.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-21302},
	author = {Schuerch, Kaspar and Woods, Russell L and Lee, Winston and Duncker, Tobias and Delori, Fran{\c c}ois C and Allikmets, Rando and Tsang, Stephen H and Sparrow, Janet R}
}
@article {382436,
	title = {Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt{\textquoteright}s macular dystrophy: follow-up of two open-label phase 1/2 studies.},
	journal = {Lancet},
	volume = {385},
	number = {9967},
	year = {2015},
	month = {2015 Feb 7},
	pages = {509-16},
	abstract = {BACKGROUND: Since they were first derived more than three decades ago, embryonic stem cells have been proposed as a source of replacement cells in regenerative medicine, but their plasticity and unlimited capacity for self-renewal raises concerns about their safety, including tumour formation ability, potential immune rejection, and the risk of differentiating into unwanted cell types. We report the medium-term to long-term safety of cells derived from human embryonic stem cells (hESC) transplanted into patients. METHODS: In the USA, two prospective phase 1/2 studies were done to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt{\textquoteright}s macular dystrophy (age \&gt;18 years) and nine with atrophic age-related macular degeneration (age \&gt;55 years). Three dose cohorts (50,000, 100,000, and 150,000 cells) were treated for each eye disorder. Transplanted patients were followed up for a median of 22 months by use of serial systemic, ophthalmic, and imaging examinations. The studies are registered with ClinicalTrials.gov, numbers NCT01345006 (Stargardt{\textquoteright}s macular dystrophy) and NCT01344993 (age-related macular degeneration). FINDINGS: There was no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events were associated with vitreoretinal surgery and immunosuppression. 13 (72\%) of 18 patients had patches of increasing subretinal pigmentation consistent with transplanted retinal pigment epithelium. Best-corrected visual acuity, monitored as part of the safety protocol, improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, whereas the untreated fellow eyes did not show similar improvements in visual acuity. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16-25 points 3-12 months after transplantation in patients with atrophic age-related macular degeneration and 8-20 points in patients with Stargardt{\textquoteright}s macular dystrophy. INTERPRETATION: The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease. Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement. FUNDING: Advanced Cell Technology.},
	keywords = {Adult, Aged, Aged, 80 and over, Cell Differentiation, Embryonic Stem Cells, Female, Follow-Up Studies, Humans, Macular Degeneration, Male, Middle Aged, Prospective Studies, Quality of Life, Retinal Pigment Epithelium, Treatment Outcome, Visual Acuity, Young Adult},
	issn = {1474-547X},
	doi = {10.1016/S0140-6736(14)61376-3},
	author = {Schwartz, Steven D and Regillo, Carl D and Lam, Byron L and Eliott, Dean and Rosenfeld, Philip J and Gregori, Ninel Z and Hubschman, Jean-Pierre and Davis, Janet L and Heilwell, Gad and Spirn, Marc and Maguire, Joseph and Gay, Roger and Bateman, Jane and Ostrick, Rosaleen M and Morris, Debra and Vincent, Matthew and Anglade, Eddy and Del Priore, Lucian V and Lanza, Robert}
}
@article {1789236,
	title = {Classification of traumatic injury to the dural venous sinus using CT venography},
	journal = {J Neuroimaging},
	year = {2023},
	month = {2023 Dec 25},
	abstract = {BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis (CVST) is an underrecognized cause of morbidity in acute traumatic brain injury (TBI). Radiologic diagnosis is challenging in the setting of concurrent extra-axial injury and a lack of standardized diagnostic criteria. The prevalence of traumatic thrombosis versus compression is unknown. Treatment with anticoagulation is often determined by the appropriate classification of the type of traumatic venous injury.

METHODS: We developed a two-part radiologic grading method for standardized assessment of traumatic CVST based on (1) the degree of flow limitation through the affected sinus and (2) the location of venous pathology (ie, external compression vs. intrinsic thrombosis) based on computed tomography venography. We applied this grading method to a retrospective cohort of TBI patients presenting to a Level 1 Trauma center. Chart review was performed to identify potential clinical correlates. A senior neuroradiologist graded the entire cohort and a random subsample was selected for blinded rating by two independent neuroradiologists.

RESULTS: Seventy-six of 221 patients were identified for inclusion after excluding nontraumatic mechanisms. Seven unique grades were employed to characterize the full extent of venous injuries. The plurality of patients from the cohort (43/76 = 43.4\%) suffered compressive injuries. Inter-rater reliability was moderate for the combined grade, kappa = 0.48, p\&lt;.05, and substantial for the flow limitation component, kappa = 0.69, p\&lt;.05.

CONCLUSIONS: We introduce a standardized two-part classification system for traumatic venous sinus injury with moderate-substantial inter-rater reliability. Compressive injuries were more common than thrombotic injuries. Further prospective work is needed to validate the clinical significance of this classification system.},
	issn = {1552-6569},
	doi = {10.1111/jon.13182},
	author = {Schwartz, Daniel A and Talbott, Jason and Callen, Andrew and Laguna, Benjamin and Narvid, Jared and Ch{\textquoteright}ang, Judy H and Singh, Vineeta}
}
@article {1806616,
	title = {Global diversity of enterococci and description of 18 previously unknown species},
	journal = {Proc Natl Acad Sci U S A},
	volume = {121},
	number = {10},
	year = {2024},
	month = {2024 Mar 05},
	pages = {e2310852121},
	abstract = {Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by \&gt;25\%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.},
	keywords = {Animals, Anti-Bacterial Agents, Drug Resistance, Bacterial, Enterococcus, Enterococcus faecalis, Enterococcus faecium, Gram-Positive Bacterial Infections, Humans, Microbial Sensitivity Tests, Phylogeny},
	issn = {1091-6490},
	doi = {10.1073/pnas.2310852121},
	author = {Schwartzman, Julia A and Lebreton, Francois and Salamzade, Rauf and Shea, Terrance and Martin, Melissa J and Schaufler, Katharina and Urhan, Aysun and Abeel, Thomas and Camargo, Ilana L B C and Sgardioli, Bruna F and Prichula, Janira and Frazzon, Ana Paula Guedes and Giribet, Gonzalo and Van Tyne, Daria and Treinish, Gregg and Innis, Charles J and Wagenaar, Jaap A and Whipple, Ryan M and Manson, Abigail L and Earl, Ashlee M and Gilmore, Michael S}
}
@article {1490458,
	title = {Expanding the phenotypic spectrum in RDH12-associated retinal disease},
	journal = {Cold Spring Harb Mol Case Stud},
	volume = {6},
	number = {1},
	year = {2020},
	month = {2020 Feb},
	abstract = {Retinol dehydrogenase 12, RDH12, plays a pivotal role in the visual cycle to ensure the maintenance of normal vision. Alterations in activity of this protein result in photoreceptor death and decreased vision beginning at an early age and progressing to substantial vision loss later in life. Here we describe 11 patients with retinal degeneration that underwent next-generation sequencing (NGS) with a targeted panel of all currently known inherited retinal degeneration (IRD) genes and whole-exome sequencing to identify the genetic causality of their retinal disease. These patients display a range of phenotypic severity prompting clinical diagnoses of macular dystrophy, cone-rod dystrophy, retinitis pigmentosa, and early-onset severe retinal dystrophy all attributed to biallelic recessive mutations in We report 15 causal alleles and expand the repertoire of known mutations with four novel variants: c.215A \&gt; G (p.Asp72Gly); c.362T \&gt; C (p.Ile121Thr); c.440A \&gt; C (p.Asn147Thr); and c.697G \&gt; A (p.Val233Ille). The broad phenotypic spectrum observed with biallelic mutations has been observed in other genetic forms of IRDs, but the diversity is particularly notable here given the prior association of primarily with severe early-onset disease. This breadth emphasizes the importance of broad genetic testing for inherited retinal disorders and extends the pool of individuals who may benefit from imminent gene-targeted therapies.},
	issn = {2373-2873},
	doi = {10.1101/mcs.a004754},
	author = {Scott, Hilary A and Place, Emily M and Ferenchak, Kevin and Zampaglione, Erin and Wagner, Naomi E and Chao, Katherine R and DiTroia, Stephanie P and Navarro-Gomez, Daniel and Mukai, Shizuo and Huckfeldt, Rachel M and Pierce, Eric A and Bujakowska, Kinga M}
}
@article {1043266,
	title = {A Young Woman With Headaches and Blurry Vision},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {6},
	year = {2017},
	month = {2017 Jun 01},
	pages = {663-664},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.4895},
	author = {Scott, Nathan L and Stryjewski, Tomasz P and Rizzo, Joseph F}
}
@article {1623365,
	title = {A hidden structural variation in a known IRD gene: a cautionary tale of two new disease candidate genes},
	journal = {Cold Spring Harb Mol Case Stud},
	volume = {8},
	number = {2},
	year = {2022},
	month = {2022 Feb},
	abstract = {Rod-cone dystrophy (RCD), also known as retinitis pigmentosa, is an inherited condition leading to vision loss, affecting 1 in 3500 people. More than 270 genes are known to be implicated in the inherited retinal degenerations (IRDs), yet genetic diagnosis for \~{}30\% of IRD of patients remains elusive despite advances in sequencing technologies. The goal of this study was to determine the genetic causality in a family with RCD. Family members were given a full ophthalmic exam at the Retinal Service at Massachusetts Eye and Ear and consented to genetic testing. Whole-exome sequencing (WES) was performed and variants of interest were Sanger-validated. Functional assays were conducted in zebrafish along with splicing assays in relevant cell lines to determine the impact on retinal function. WES identified variants in two potential candidate genes that segregated with disease: GNL3 (G Protein Nucleolar 3) c.1187 + 3A \&gt; C and c.1568-8C \&gt; A; and PDE4DIP (Phosphodiester 4D Interacting Protein) c.3868G \&gt; A (p.Glu1290Lys) and c.4603G \&gt; A (p.Ala1535Thr). Both genes were promising candidates based on their retinal involvement (development and interactions with IRD-associated proteins); however, the functional assays did not validate either gene. Subsequent WES reanalysis with an updated bioinformatics pipeline and widened search parameters led to the detection of a 94-bp duplication in PRPF31 (pre-mRNA Processing Factor 31) c.73_266dup (p.Asp56GlyfsTer33) as the causal variant. Our study demonstrates the importance of thorough functional characterization of new disease candidate genes and the value of reanalyzing next-generation sequencing sequence data, which in our case led to identification of a hidden pathogenic variant in a known IRD gene.},
	issn = {2373-2873},
	doi = {10.1101/mcs.a006131},
	author = {Scott, Hilary A and Larson, Anna and Rong, Shi Song and Mehrotra, Sudeep and Butcher, Rossano and Chao, Katherine R and Wiggs, Janey L and Place, Emily M and Pierce, Eric A and Bujakowska, Kinga M}
}
@article {280931,
	title = {Endothelial progenitor cells and response to ranibizumab in age-related macular degeneration.},
	journal = {Retina},
	volume = {34},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1802-10},
	abstract = {BACKGROUND: Choroidal neovascularization (CNV) is the main cause of vision loss in age-related macular degeneration (AMD). In experimental CNV, endothelial progenitor cells (EPCs) contribute to the formation of new vessels. The aim of this study was to investigate whether the behavior of EPCs in patients with AMD supports a role for EPCs in human CNV. METHODS: The number of circulating EPCs that are considered pure endothelial precursors and EPCs with monocytic characteristics, and the plasma levels of regulatory cytokines were evaluated in 23 patients with AMD with active CNV and 20 matched controls. In the patients, this profile was re-evaluated after ranibizumab. RESULTS: When compared with controls, the patients with AMD showed a lower number of both EPC types (P = 0.03) and higher plasma levels (P = 0.03) of stromal cell-derived factor 1. Three monthly injections of ranibizumab returned to control levels the number of circulating EPCs considered pure endothelial precursors and of stromal cell-derived factor 1, but not of monocytic EPCs. CONCLUSION: The observations indicate responsiveness of circulating EPCs to the CNV process in AMD. They suggest the hypothesis that increased stromal cell-derived factor 1 production at the CNV site (reflected in higher plasma levels) recruits EPCs from the circulation, and that antivascular endothelial growth factor therapy selectively decreases the recruitment of cells to be incorporated into new vessels.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000147},
	author = {Scotti, Fabrizio and Maestroni, Anna and Palini, Alessio and Introini, Ugo and Setaccioli, Marco and Lorenzi, Mara and Zerbini, Gianpaolo}
}
@article {1452977,
	title = {Great Conversations: Dr. Barrett Katz},
	journal = {J Neuroophthalmol},
	volume = {39},
	number = {3},
	year = {2019},
	month = {2019 Sep},
	pages = {e13-e14},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000816},
	author = {Seay, Meagan and Fortin, Elizabeth and Digre, Kathleen}
}
@article {1789226,
	title = {Feasibility and Potential for Real-Time 3D Vitreoretinal Surgery Telementoring},
	journal = {Retina},
	volume = {43},
	number = {12},
	year = {2023},
	month = {2023 Dec 01},
	pages = {2162-2165},
	abstract = {PURPOSE: To demonstrate the potential for real-time, three-dimensional (3D) surgical telementoring to enhance vitreoretinal surgical education.

METHODS: The 3D video feed from a high dynamic range surgical camera (NGENUITY) was run through a 4K video capture device (Magewell USB 4K) and set as the video input for a video conferencing application (Zoom). Remote surgical viewing was then performed in two-dimensions (2D) on a computer or in 3D with a virtual reality headset (Oculus Quest 2).

RESULTS: Ten surgical cases were successfully live streamed in real time to two separate surgeons in the United States. Specific details of the case were visualized with low latency and interaction with the operating surgeon was possible without affecting the surgical display quality. Excluding the NGENUITY system and personal computers, ancillary equipment costs (video capture card and virtual reality headset) were kept to below $1,000.

CONCLUSION: Our study demonstrates that 3D surgical video streaming can be achieved in real time with minimal latency through the use of low-cost video capture equipment and video conferencing/streaming software. The use of this technology gives educators the ability to mentor trainees without the traditional geographic and physical constraints of in-person surgical viewing.},
	keywords = {Feasibility Studies, Humans, Software, United States, Vitreoretinal Surgery},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003656},
	author = {Seddon, Ian A and Rahimy, Ehsan and Miller, John B and Charles, Steve and Kitchens, John and Houston, Samuel Kenney}
}
@article {1773466,
	title = {Computer versus human-expert ranking of posterior pole vascular tortuosity and dilation using retinal vessel maps generated from bedside optical coherence tomography: a proof-of-concept study},
	journal = {J AAPOS},
	volume = {27},
	number = {6},
	year = {2023},
	month = {2023 Dec},
	pages = {351-354},
	abstract = {Semiautomated computer software (ie, ROPtool) can trace and analyze optical coherence tomography (OCT)-generated retinal vessel maps for plus/pre-plus disease with high reliability and accuracy. This proof-of-concept study found that ROPtool can reliably rank OCT-generated vessel maps for tortuosity and combined tortuosity/dilation, which correlated well with human-expert rankings and clinical examination.},
	keywords = {Computers, Diagnosis, Computer-Assisted, Dilatation, Dilatation, Pathologic, Humans, Infant, Newborn, Reproducibility of Results, Retinal Vessels, Retinopathy of Prematurity, Tomography, Optical Coherence},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.08.009},
	author = {Seely, Kai R and Freedman, Sharon F and Grace, Sara and Weinert, Marguerite C and Hong, Gloria J and Toth, Cynthia A and Grace Prakalapakorn, S}
}
@article {1645455,
	title = {Semi-automated vessel analysis of en face posterior pole vessel maps generated from optical coherence tomography for diagnosis of plus or pre-plus disease},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Jun 03},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.03.008},
	author = {Seely, Kai R and Weinert, Marguerite C and Hong, Gloria J and Wang, Weiliang and Grace, Sara and Freedman, Sharon F and Toth, Cynthia A and Prakalapakorn, S Grace}
}
@article {913516,
	title = {Electrical Stimulation as a Means for Improving Vision.},
	journal = {Am J Pathol},
	volume = {186},
	number = {11},
	year = {2016},
	month = {2016 Nov},
	pages = {2783-2797},
	abstract = {Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2016.07.017},
	author = {Sehic, Amer and Guo, Shuai and Cho, Kin-Sang and Corraya, Rima M and Chen, Dong F and Utheim, Tor P}
}
@article {1645481,
	title = {Impact of the Affordable Care Act on Glaucoma Severity at First Presentation},
	journal = {Ophthalmic Epidemiol},
	volume = {30},
	number = {3},
	year = {2023},
	month = {2023 Jun},
	pages = {326-329},
	abstract = {PURPOSE: To test whether the increase in insurance coverage in Massachusetts due to the Affordable Care Act (ACA) is associated with a decrease in glaucoma severity in patients presenting for the first time at a tertiary health system. METHODS: Clinical and billing data of first-time glaucoma patients from a tertiary health system in Massachusetts from 2006 to 2021 was used. Pre-ACA is defined as before 2014 and post-ACA is defined as after 2014. Visual field mean deviation was used to define glaucoma severity: greater than -6 dB, less than -6 dB and greater than -12 dB, and less than -12 dB was classified as "mild," "moderate," and "severe" respectively. Ordinal logistic regression models adjusted for age, race, gender, and insurance type were used to determine the odds of presenting with more severe glaucoma. RESULTS: 2,394 pre-ACA and 3,651 post-ACA first-time glaucoma patients were identified. There was no significant difference in the likelihood of more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.96; 95\% CI 0.86-1.08; p=0.49) among the entire population. In stratified analyses, patients who utilized Medicaid for insurance had 52\% decreased odds for presenting with more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.48; 95\% CI 0.33-0.69; p\&lt;0.001). This remained significant after adjustment for age, race, and gender (adjusted OR=0.44; 95\% CI 0.29-0.65; p\&lt;0.001). CONCLUSION: At a Massachusetts-based tertiary healthcare center, individuals on Medicaid were more likely to have more severe glaucoma at first presentation before the implementation of the ACA, compared to after.},
	keywords = {Humans, Insurance Coverage, Insurance, Health, Medicaid, Patient Protection and Affordable Care Act, Tertiary Care Centers, United States},
	issn = {1744-5086},
	doi = {10.1080/09286586.2022.2089357},
	author = {Sekimitsu, Sayuri and Tobias Elze and Zebardast, Nazlee}
}
@article {1748396,
	title = {Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {9},
	year = {2023},
	month = {2023 Sep 01},
	pages = {891-899},
	abstract = {IMPORTANCE: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. OBJECTIVE: To evaluate phenotypic features across genetic burden for POAG. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. MAIN OUTCOMES AND MEASURES: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. RESULTS: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8\%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4\% (3005 of 40 644) vs 1.3\% (544 of 40 795) in lowest decile (P \&lt; .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95\% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95\% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95\% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95\% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95\% CI, -0.11 to -0.07; P \&lt; .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 μm and macular ganglion cell complex (GCC) of 0.26 μm (P \&lt; .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95\% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95\% CI, 0.012-0.014; P \&lt; .001 for both). A total of 22 of 5193 fundus photographs (0.4\%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5\%) had suspicious optic disc features compared with 9 of 5158 (0.2\%) and 10 of 5219 (0.2\%), respectively, in decile 1 (P \&lt; .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P \&lt; .001). CONCLUSION AND RELEVANCE: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.},
	keywords = {Cornea, Cross-Sectional Studies, Glaucoma, Glaucoma, Open-Angle, Hemorrhage, Humans, Middle Aged},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.3645},
	author = {Sekimitsu, Sayuri and Xiang, David and Smith, Sophie Lloyd and Curran, Katie and Tobias Elze and Friedman, David S and Foster, Paul J and Luo, Yuyang and Pasquale, Louis R and Peto, Tunde and Segr{\`e}, Ayellet V and Shweikh, Yusrah and Warwick, Alasdair and Zhao, Yan and Wiggs, Janey L and Zebardast, Nazlee and UK Biobank Eye and Vision Consortium}
}
@article {1677806,
	title = {Association of retinal optical coherence tomography metrics and polygenic risk scores with cognitive function and future cognitive decline},
	journal = {Br J Ophthalmol},
	year = {2023},
	month = {2023 Mar 29},
	abstract = {PURPOSE: To evaluate the potential of retinal optical coherence tomography (OCT) measurements and polygenic risk scores (PRS) to identify people at risk of cognitive impairment. METHODS: Using OCT images from 50 342 UK Biobank participants, we examined associations between retinal layer thickness and genetic risk for neurodegenerative disease and combined these metrics with PRS to predict baseline cognitive function and future cognitive deterioration. Multivariate Cox proportional hazard models were used to predict cognitive performance. P values for retinal thickness analyses are false-discovery-rate-adjusted. RESULTS: Higher Alzheimer{\textquoteright}s disease PRS was associated with a thicker inner nuclear layer (INL), chorio-scleral interface (CSI) and inner plexiform layer (IPL) (all p\&lt;0.05). Higher Parkinson{\textquoteright}s disease PRS was associated with thinner outer plexiform layer (p\&lt;0.001). Worse baseline cognitive performance was associated with thinner retinal nerve fibre layer (RNFL) (aOR=1.038, 95\% CI (1.029 to 1.047), p\&lt;0.001) and photoreceptor (PR) segment (aOR=1.035, 95\% CI (1.019 to 1.051), p\&lt;0.001), ganglion cell complex (aOR=1.007, 95\% CI (1.002 to 1.013), p=0.004) and thicker ganglion cell layer (aOR=0.981, 95\% CI (0.967 to 0.995), p=0.009), IPL (aOR=0.976, 95\% CI (0.961 to 0.992), p=0.003), INL (aOR=0.923, 95\% CI (0.905 to 0.941), p\&lt;0.001) and CSI (aOR=0.998, 95\% CI (0.997 to 0.999), p\&lt;0.001). Worse future cognitive performance was associated with thicker IPL (aOR=0.945, 95\% CI (0.915 to 0.999), p=0.045) and CSI (aOR=0.996, 95\% CI (0.993 to 0.999) 95\% CI, p=0.014). Prediction of cognitive decline was significantly improved with the addition of PRS and retinal measurements. CONCLUSIONS AND RELEVANCE: Retinal OCT measurements are significantly associated with genetic risk of neurodegenerative disease and may serve as biomarkers predictive of future cognitive impairment.},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-322762},
	author = {Sekimitsu, Sayuri and Shweikh, Yusrah and Shareef, Sarah and Zhao, Yan and Tobias Elze and Segr{\`e}, Ayellet and Wiggs, Janey and Zebardast, Nazlee}
}
@article {1645482,
	title = {Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank},
	journal = {PLoS One},
	volume = {17},
	number = {6},
	year = {2022},
	month = {2022},
	pages = {e0270530},
	abstract = {BACKGROUND/AIMS: Psychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure. METHODS: This analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method. RESULTS: Among the 441,054 participants, 959 (0.22\%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24{\textpm}1.03 SD vs. 0.00{\textpm}1.00 SD, p\&lt;0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31{\textpm}1.00 SD vs. 0.00{\textpm}1.00 SD, p\&lt;0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles. CONCLUSION: We demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.},
	keywords = {Biological Specimen Banks, Genome-Wide Association Study, Glaucoma, Angle-Closure, Humans, Prospective Studies, Psychotropic Drugs, Risk Factors, United Kingdom},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0270530},
	author = {Sekimitsu, Sayuri and Wang, Jiali and Tobias Elze and Segr{\`e}, Ayellet V and Wiggs, Janey L and Zebardast, Nazlee}
}
@article {1405415,
	title = {Outcomes After Comprehensive Vision Rehabilitation Using Vision-related Quality of Life Questionnaires: Impact of Vision Impairment and National Eye Institute Visual Functioning Questionnaire},
	journal = {Optom Vis Sci},
	volume = {96},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {87-94},
	abstract = {SIGNIFICANCE: This research is significant because, although vision-related quality of life (VRQoL) is improved after vision rehabilitation (VR), patients with certain characteristics respond less positively on VRQoL measures, and this should inform future care. PURPOSE: The purposes of this study were to evaluate how two VRQoL questionnaires compare in measuring change in patient-reported outcomes after VR and to determine if patient characteristics or occupational therapy (OT) predict higher scores after rehabilitation. METHODS: In a prospective clinical cohort study, 109 patients with low vision completed the Impact of Vision Impairment (IVI) and the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) before and after VR. Comprehensive VR included consultation with an ophthalmologist and OT if required. The relationships of six baseline characteristics (age, sex, visual acuity, contrast sensitivity, field loss, diagnosis) and OT were assessed with VRQoL scores using multivariable logistic regression. RESULTS: The mean (SD) age was 68.5 (19.2) years, and 61 (56\%) were female. After rehabilitation, increases in scores were observed in all IVI subscales (reading [P \&lt; .001], mobility [P = .002], well-being [P = .0003]) and all NEI VFQ-25 subscales (functional [P = .01], socioemotional [P = .003]). Those who were referred to OT but did not attend and those who had hemianopia/field loss were less likely to have higher VRQoL in IVI mobility and well-being. Those attending OT for more than 3 hours were less likely to have better scores in emotional NEI VFQ. Men were less likely to have increased scores in functional and emotional NEI VFQ, whereas those with diagnoses of nonmacular diseases had higher odds of having increased scores on the emotional NEI VFQ (all, P \&lt; .05). CONCLUSION: Both the IVI and the NEI VFQ-25 detected change in patients{\textquoteright} VRQoL after rehabilitation. Most of the patient characteristics we considered predicted a lower likelihood of increased scores in VRQoL.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001327},
	author = {Selivanova, Alexandra and Fenwick, Eva and Man, Ryan and Seiple, William and Jackson, Mary Lou}
}
@article {882986,
	title = {Oxygen as a Virulence Determinant in Polymicrobial Infections.},
	journal = {MBio},
	volume = {7},
	number = {4},
	year = {2016},
	month = {2016},
	abstract = {Infections caused by multiple organisms, or polymicrobial infections, are likely more common than is broadly appreciated. Interaction among microbial communities (and with their host) can change the infection landscape by subverting immunity, providing nutrients and inhibiting competing microbes. Stacy et al. (A. Stacy, D. Fleming, R. J. Lamont, K. P. Rumbaugh, and M. Whiteley, mBio 7:e00782-16, 2016, http://dx.doi.org/10.1128/mBio.00782-16) described a novel mechanism that results in synergistic growth of oral microbes Aggregatibacter actinomycetemcomitans and Streptococcus gordonii The authors used whole-genome fitness profiling by transposon sequencing (Tn-seq) to identify genes differentially required for growth in vitro versus in a mono- or coinfection in a thigh abscess model. They found that coinfection with S.\&nbsp;gordonii allowed A.\&nbsp;actinomycetemcomitans to shift from an anaerobic to an aerobic mode of growth. This shift involved the production of a terminal electron acceptor H2O2 by S.\&nbsp;gordonii and increased A.\&nbsp;actinomycetemcomitans persistence-an interaction termed "cross-respiration."},
	issn = {2150-7511},
	doi = {10.1128/mBio.01249-16},
	author = {Selleck, Elizabeth M and Gilmore, Michael S}
}
@article {1647884,
	title = {Juvenile-onset open-angle glaucoma - A clinical and genetic update},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {4},
	year = {2022},
	month = {2022 Jul-Aug},
	pages = {1099-1117},
	abstract = {Juvenile-onset open-angle glaucoma (JOAG) is a subset of primary open-angle glaucoma that is diagnosed before 40 years of age. The disease may be familial or non-familial, with proportions varying among different populations. Myocilin mutations are the most commonly associated. JOAG is characterized by high intraocular pressures (IOP), with many patients needing surgery. The mean age at diagnosis is in the 3rd decade, with a male preponderance. Myopia is a common association. The pathophysiology underlying the disease is immaturity of the conventional outflow pathways, which may or may not be observed on gonioscopy and anterior segment optical coherence tomography. The unique optic nerve head features include large discs with deep, steep cupping associated with high IOP-induced damage. Progression rates among JOAG patients are comparable to adult primary glaucomas, but as the disease affects younger patients, the projected disability from this disease is higher. Early diagnosis, prompt management, and life-long monitoring play an important role in preventing disease progression. Gene-based therapies currently under investigation offer future hope.},
	keywords = {Adult, Eye Proteins, Glaucoma, Glaucoma, Open-Angle, Gonioscopy, Humans, Intraocular Pressure, Male, Mutation, Optic Disk},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2021.09.001},
	author = {Selvan, Harathy and Gupta, Shikha and Wiggs, Janey L and Gupta, Viney}
}
@article {1498255,
	title = {Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults},
	journal = {J Am Acad Dermatol},
	volume = {82},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {1553-1567},
	abstract = {Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of <=1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid\&nbsp;and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.},
	issn = {1097-6787},
	doi = {10.1016/j.jaad.2020.02.066},
	author = {Seminario-Vidal, Lucia and Kroshinsky, Daniela and Malachowski, Stephen J and Sun, James and Markova, Alina and Beachkofsky, Thomas M and Kaffenberger, Benjamin H and Ergen, Elizabeth N and Mauskar, Melissa and Bridges, Alina and Calhoun, Cody and Cardones, Adela R and Chen, Steven T and Chodosh, James and Cotliar, Jonathan and Davis, Mark D P and DeNiro, Katherine L and Dominguez, Arturo R and Eljure-T{\'e}llez, Juliana and Femia, Alisa and Fox, Lindy P and Guda, Anisha and Mitchell, Caroline and Mostaghimi, Arash and Ortega-Loayza, Alex G and Owen, Cindy and Pasieka, Helena and Rahnama-Moghadam, Sahand and Saeed, Hajirah N and Saunderson, Rebecca B and Shanbhag, Swapna and Sharon, Victoria R and Strowd, Lindsay and Venkatesh, Samantha and Wanat, Karolyn A and Wetter, David A and Worswick, Scott and Micheletti, Robert G}
}
@article {836961,
	title = {Efficacy and Safety of Human Retinal Progenitor Cells.},
	journal = {Transl Vis Sci Technol},
	volume = {5},
	number = {4},
	year = {2016},
	month = {2016 Jul},
	pages = {6},
	abstract = {PURPOSE: We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. METHODS: Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. RESULTS: The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. CONCLUSIONS: Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. TRANSLATIONAL RELEVANCE: Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies.},
	issn = {2164-2591},
	doi = {10.1167/tvst.5.4.6},
	author = {Semo, Ma{\textquoteright}ayan and Haamedi, Nasrin and Stevanato, Lara and Carter, David and Brooke, Gary and Young, Michael and Coffey, Peter and Sinden, John and Patel, Sara and Vugler, Anthony}
}
@article {313151,
	title = {Periocular corticosteroid injections in uveitis: effects and complications},
	journal = {Ophthalmology},
	volume = {121},
	number = {11},
	year = {2014},
	month = {2014 Nov},
	pages = {2275-86},
	abstract = {PURPOSE: To evaluate the benefits and complications of periocular depot corticosteroid injections in patients with ocular inflammatory disorders. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: A total of 914 patients (1192 eyes) who had received >= 1 periocular corticosteroid injection at 5 tertiary uveitis clinics in the United States. METHODS: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained at every visit via medical record review by trained reviewers. MAIN OUTCOME MEASURES: Control of inflammation, improvement of visual acuity (VA) to >= 20/40, improvement of VA loss attributed to macular edema (ME), incident cataract affecting VA, cataract surgery, ocular hypertension, and glaucoma surgery. RESULTS: Among 914 patients (1192 eyes) who received >= 1 periocular injection during follow-up, 286 (31.3\%) were classified as having anterior uveitis, 303 (33.3\%) as intermediate uveitis, and 324 (35.4\%) as posterior or panuveitis. Cumulatively by <= 6 months, 72.7\% (95\% CI, 69.1-76.3) of the eyes achieved complete control of inflammation and 49.7\% (95\% CI, 45.5-54.1) showed an improvement in VA from \&lt;20/40 to >= 20/40. Among the subset with VA \&lt;20/40 attributed to ME, 33.1\% (95\% CI, 25.2-42.7) improved to >= 20/40. By 12 months, the cumulative incidence of >= 1 visits with an intraocular pressure of >= 24 mmHg and >= 30 mmHg was 34.0\% (95\% CI, 24.8-45.4) and 15.0\% (95\% CI, 11.8-19.1) respectively; glaucoma surgery was performed in 2.4\% of eyes (95\% CI, 1.4-3.9). Within 12 months, among phakic eyes initially >= 20/40, the incidence of a reduction in VA to \&lt;20/40 attributed to cataract was 20.2\% (95\% CI, 15.9-25.6); cataract surgery was performed within 12 months in 13.8\% of the initially phakic eyes (95\% CI, 11.1-17.2). CONCLUSIONS: Periocular injections were effective in treating active intraocular inflammation and in improving reduced VA attributed to ME in a majority of patients. The response pattern was similar across anatomic locations of uveitis. Overall, VA improved in one half of the patients at some point within 6 months. However, cataract and ocular hypertension occurred in a substantial minority.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Glucocorticoids, Humans, Infant, Infant, Newborn, Injections, Intraocular, Male, Middle Aged, Retrospective Studies, Triamcinolone Acetonide, Uveitis, Visual Acuity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.05.021},
	author = {Sen, H Nida and Vitale, Susan and Gangaputra, Sapna S and Nussenblatt, Robert B and Liesegang, Teresa L and Levy-Clarke, Grace A and Rosenbaum, James T and Suhler, Eric B and Thorne, Jennifer E and Foster, C Stephen and Jabs, Douglas A and Kempen, John H}
}
@article {1623377,
	title = {Pneumatic retinopexy versus scleral buckle for repairing simple rhegmatogenous retinal detachments},
	journal = {Cochrane Database Syst Rev},
	volume = {11},
	year = {2021},
	month = {2021 Nov 11},
	pages = {CD008350},
	abstract = {BACKGROUND: A rhegmatogenous retinal detachment (RRD) is a separation of the neurosensory retina from the retinal pigment epithelium caused by a full-thickness break associated with vitreous traction. While pneumatic retinopexy (PR), scleral buckle (SB), and vitrectomy are all well-received surgical interventions for eyes with RRD, their relative effectiveness has remained controversial. OBJECTIVES: To assess\&nbsp;the\&nbsp;effectiveness and safety of PR versus SB or PR versus a combination treatment of SB and vitrectomy for people with RRD and to summarize any data on economic measures and quality of life. SEARCH METHODS: We searched CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 3); Ovid MEDLINE; Ovid Embase; and four other databases on 11 March 2021. We used no date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included all randomized or quasi-randomized controlled trials comparing the effectiveness of PR versus SB (with or without vitrectomy) for eyes with RRD. DATA COLLECTION AND ANALYSIS: After screening for eligibility, two review authors independently extracted study characteristics, methods, and outcomes. We followed systematic review standards as set by Cochrane. MAIN RESULTS: In this update, we identified and included one new randomized controlled trial. Together with two trials from the 2015 version of the review, we included three\&nbsp;trials (276\&nbsp;eyes of 274\&nbsp;participants) comparing the effectiveness of PR versus SB. None compared PR versus a combined treatment of SB and vitrectomy.\&nbsp; Of the three trials, one was a small study (published in 1996) with 20 participants (20 eyes) enrolled in Ireland and followed for a mean of 16 months; the second (published in 1989) included 196 participants (198 eyes) in the US followed for at least six months, and the third (published in 2021) was conducted in Italy and enrolled 58 participants (58 eyes) with a follow-up of 12 months. Overall, poor reporting quality resulted in unclear or high risks of bias.\&nbsp; We found low-certainty evidence that\&nbsp;PR may achieve retinal reattachment slightly less often than SB (risk ratio [RR] 0.91, 95\% confidence interval [CI] 0.81 to 1.02; I2 = 0\%; 3 studies, 276 eyes). Eyes undergoing PR\&nbsp;may also display a higher risk of recurrent retinal detachment (low-certainty evidence), but the RR estimates were very imprecise\&nbsp;(RR 1.70, 95\% CI 0.97 to 2.98; I2 = 0\%; 3 studies, 276 eyes). All three studies described the final\&nbsp;visual acuity (VA) after the two procedures.\&nbsp;However, the results were reported using different metrics and could not be combined. One study (196 participants) reported the proportion of eyes with a final VA of 20/40 or greater and favored PR (RR 1.31, 95\% CI 1.04 to 1.65; low-certainty evidence), whereas in the 2021 study, both groups showed an improvement in final VA and there was no evidence of a difference between the two (mean difference [MD] -0.03, 95\% CI -0.25 to 0.19; low-certainty evidence). No study reported data on\&nbsp;quality of life\&nbsp;or economic measures. Postoperative safety outcomes generally favored PR versus SB (low/very low-certainty evidence); however, there was considerable uncertainty regarding the risk of any operative ocular adverse events (RR 0.55 CI 0.28 to 1.11; 276\&nbsp;eyes),\&nbsp;glaucoma (RR 0.31, 95\% CI 0.01 to 7.46; 198 eyes),\&nbsp;macular pucker (RR 0.65, 95\% CI 0.20 to 2.11; 256\&nbsp;eyes),\&nbsp;proliferative vitreoretinopathy (RR 0.94, 95\% CI 0.30 to 2.96; 276\&nbsp;eyes), and persistent diplopia (RR 0.24, 95\% CI 0.03 to 2.09; 256 eyes).\&nbsp;Eyes undergoing PR experienced fewer postoperative cataract developments (RR 0.40, 95\% CI 0.21 to 0.75; 153\&nbsp;eyes),\&nbsp;choroidal detachments (RR 0.17, 95\% CI 0.05 to 0.57; 198 eyes), and\&nbsp;myopic shift\&nbsp;(RR 0.03, 95\% CI 0.01 to 0.10; 256 eyes). AUTHORS{\textquoteright} CONCLUSIONS: The current update confirms the findings of the previous review. PR may result in lower rates of reattachment and higher rates of recurrence than SB, but carries a lower burden of postoperative complications. The effects of these two procedures on\&nbsp;other functional outcomes and quality of life remain\&nbsp;uncertain.\&nbsp;The available\&nbsp;evidence remains insufficient and of low quality.},
	issn = {1469-493X},
	doi = {10.1002/14651858.CD008350.pub3},
	author = {Sena, Dayse F and Kilian, Raphael and Liu, Su-Hsun and Rizzo, Stanislao and Virgili, Gianni}
}
@article {1351186,
	title = {Activation of HIF-1α (hypoxia inducible factor-1α) prevents dry eye-induced acinar cell death in the lacrimal gland},
	journal = {Cell Death Dis},
	volume = {5},
	year = {2014},
	month = {2014 Jun 26},
	pages = {e1309},
	abstract = {The pathogenesis of immune-mediated lacrimal gland (LG) dysfunction in Sj{\"o}gren{\textquoteright}s syndrome has been thoroughly studied. However, the majority of dry eye (DE) is not related to Sj{\"o}gren type, and its pathophysiology remains unclear. The purpose of this study was to determine and investigate the protective mechanisms against DE stress in mice. DE induced prominent blood vessel loss without apoptosis or necrosis in the LG. Autophagic vacuoles, distressed mitochondria, and stressed endoplasmic reticulum were observed via electron microscopy. Immunoblotting confirmed the increase in autophagic markers. Glycolytic activities were enhanced with increasing levels of succinate and malate that, in turn, activated hypoxia-inducible factor (HIF)-1α. Interestingly, the areas of stable HIF-1α expression overlapped with COX-2 and MMP-9 upregulation in LGs of DE-induced mice. We generated HIF-1α conditional knockout (CKO) mice in which HIF-1α expression was lost in the LG. Surprisingly, normal LG polarities and morphologies were completely lost with DE induction, and tremendous acinar cell apoptosis was observed. Similar to Sj{\"o}gren{\textquoteright}s syndrome, CD3(+) and CD11b(+) cells infiltrated HIF-1α CKO LGs. Our results show that DE induced the expression of HIF-1α that activated autophagy signals to prevent further acinar cell damage and to maintain normal LG function.},
	keywords = {Animals, Autophagy, Cyclooxygenase 2, Female, Hypoxia-Inducible Factor 1, alpha Subunit, Lacrimal Apparatus, Matrix Metalloproteinase 9, Mice, Mice, Knockout, Sjogren{\textquoteright}s Syndrome},
	issn = {2041-4889},
	doi = {10.1038/cddis.2014.260},
	author = {Seo, Y and Ji, Y W and Lee, S M and Shim, J and Noh, H and Yeo, A and Park, C and Park, M S and Chang, E J and Lee, H K}
}
@article {280851,
	title = {Activation of HIF-1α (hypoxia inducible factor-1α) prevents dry eye-induced acinar cell death in the lacrimal gland.},
	journal = {Cell Death Dis},
	volume = {5},
	year = {2014},
	month = {2014},
	pages = {e1421},
	issn = {2041-4889},
	doi = {10.1038/cddis.2014.382},
	author = {Seo, Y and Ji, Y W and Lee, S M and Shim, J and Noh, H and Yeo, A and Park, C and Park, M S and Chang, E J and Lee, H K}
}
@article {1647870,
	title = {Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer{\textquoteright}s dementia},
	journal = {Acta Neuropathol},
	volume = {144},
	number = {3},
	year = {2022},
	month = {2022 09},
	pages = {589-601},
	abstract = {We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer{\textquoteright}s disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer{\textquoteright}s symptoms for almost three decades beyond the expected age of onset. We identified a distinct anatomical pattern of tau pathology with atypical accumulation in vivo and unusual postmortem regional distribution characterized by sparing in the frontal cortex and severe pathology in the occipital cortex. The frontal cortex and the hippocampus, less affected than the occipital cortex by tau pathology, contained Related Orphan Receptor B (RORB) positive neurons, homeostatic astrocytes and higher APOE expression. The occipital cortex, the only cortical region showing cerebral amyloid angiopathy (CAA), exhibited a distinctive chronic inflammatory microglial profile and lower APOE expression. Thus, the Christchurch variant may\&nbsp;impact the distribution of tau pathology, modulate age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies.},
	keywords = {Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E3, Brain, Homozygote, Humans, Positron-Emission Tomography, tau Proteins},
	issn = {1432-0533},
	doi = {10.1007/s00401-022-02467-8},
	author = {Sepulveda-Falla, Diego and Sanchez, Justin S and Almeida, Maria Camila and Boassa, Daniela and Acosta-Uribe, Juliana and Vila-Castelar, Clara and Ramirez-Gomez, Liliana and Baena, Ana and Aguillon, David and Villalba-Moreno, Nelson David and Littau, Jessica Lisa and Villegas, Andres and Beach, Thomas G and White, Charles L and Mark Ellisman and Krasemann, Susanne and Glatzel, Markus and Johnson, Keith A and Sperling, Reisa A and Reiman, Eric M and Arboleda-Velasquez, Joseph F and Kosik, Kenneth S and Lopera, Francisco and Quiroz, Yakeel T}
}
@article {1470985,
	title = {Use of the Delphi process for defining successful outcomes for strabismus surgery},
	journal = {J AAPOS},
	volume = {23},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {309-312},
	abstract = {The purpose of this review was to identify areas of consensus and disagreement among experts for the definition of success following strabismus surgery using the Delphi process. Three rounds of electronic questionnaires were sent to a panel of 28 strabismus experts. Throughout the process, members of the panel were masked to one another{\textquoteright}s identities to minimize the possibility of influence among members. Prior to data collection, we defined consensus as an 85\% agreement on the answer to each question. Questions for which there was no consensus were reworded, and the resultant new questions were used in each subsequent round of questioning. We arrived at consensus for 23 of the 36 questions (64\%). Consensus was obtained for recommending unique criteria for the definition of success for certain specific strabismus conditions. In addition, it was considered important that stereopsis and the range of single binocular vision be included in the definition of success for certain types of strabismus.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.07.006},
	author = {Serafino, Massimiliano and Granet, David B and Kushner, Burton J and Dagi, Linda R and Kekunnaya, Ramesh and Nucci, Paolo}
}
@article {1580493,
	title = {Definition of successful outcomes after surgery for each type of strabismus: a Delphi study},
	journal = {J AAPOS},
	year = {2021},
	month = {2021 Feb 16},
	abstract = {BACKGROUND: The Delphi process has been widely used to delineate guidelines for the treatment of disorders for which there is little or no evidence in the published literature. The purpose of this study was to use the Delphi process to identify areas of consensus and disagreement on the definition of success after surgery for each type of strabismus. METHODS: Two rounds of electronic questionnaires were sent to 28 members of the Strabismus Success Definition Delphi Study Group. For the first round, responses to 70 questions were captured as agree (= 1) and disagree (= 2). For round 2, a total of 89 questions were captured on a Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Consensus was determined a priori at 85\%. RESULTS: In both the first and second rounds, inter-rater agreement of 85\% consensus was reached for only 20\% of questions. Intra-rater agreement per question was low, with κ values ranging from -0.11 to 0.62. Intra-rater agreement was also low among themes, ranging from poor to fair agreement: κ = 0.25 for motor, κ = 0.28 for sensory, and κ = 0.35 for follow-up. CONCLUSIONS: This study highlights consensus areas that could be considered by researchers in designing studies and identifies areas where lack of consensus indicates that further research is needed.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.08.014},
	author = {Serafino, Massimiliano and Granet, David B and Kushner, Burton J and Dagi, Linda R and Kekunnaya, Ramesh and Nucci, Paolo and Kreatsoulas, Catherine}
}
@article {1761976,
	title = {Treatment Outcomes for Juvenile Open Angle Glaucoma in Thailand},
	journal = {J Glaucoma},
	volume = {32},
	number = {11},
	year = {2023},
	month = {2023 Nov 01},
	pages = {976-982},
	abstract = {PRCIS: Juvenile open angle glaucoma (JOAG) patients with thick central corneas and negative family history were more likely to undergo surgery, mainly trabeculectomy with half requiring additional surgery within 10 years. PURPOSE: To assess the characteristics and treatment outcomes of patients with JOAG in Thailand. PATIENTS AND METHODS: This retrospective, multicenter study included all patients diagnosed with JOAG over 12 years from 2 tertiary hospitals in Bangkok, Thailand. RESULTS: A total of 200 eyes from 104 patients were included in this study. The mean age of onset was 24.0{\textpm}10.1 years (range: 5-40\&nbsp;y), with male predominance (60.5\%). Over 90\% of patients had bilateral JOAG and 25\% had a positive family history. Negative family history (adjusted odds ratio=4.59, P =0.02) and thick central corneal thickness were surgical predictors (every 10\&nbsp;{\textmu}m adjusted odds ratio=1.29, P =0.01). Over 70\% of cases needed glaucoma surgery. Trabeculectomy with Mitomycin-C was performed on 131 eyes (65.5\%) with a cumulative probability of complete success of 71.0\%, 57.8\%, 39.2\%, and 26.9\% and qualified success of 86.3\%, 73.6\%, 64.8\%, and 45.7\% at 1, 3, 5, and 10 years, respectively. The mean follow-up after surgery was 94.9 {\textpm} 69.8 months (range: 13-153\&nbsp;mo). There were no serious postoperative complications. Myopia and the number of baseline glaucoma medications were significantly associated with surgical failure. CONCLUSIONS: Trabeculectomy with mitomycin C was the most common primary surgery performed in Thai patients with JOAG, and successfully reduced intraocular pressure without significant complications. Patients with thicker corneas were more likely to undergo surgery. By 10 years, half of the patients required additional surgery and risk factors for failure included myopia and the number of medications.},
	keywords = {Adolescent, Adult, Child, Child, Preschool, Cornea, Female, Follow-Up Studies, Glaucoma, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Mitomycin, Myopia, Retrospective Studies, Thailand, Trabeculectomy, Treatment Outcome, Young Adult},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002309},
	author = {Seresirikachorn, Kasem and Thiamthat, Warakorn and Annopawong, Kornkamol and Wanichwecharungruang, Boonsong and Friedman, David S and Vu, Daniel M}
}
@article {1732701,
	title = {Two types of childhood glaucoma secondary to familial exudative vitreoretinopathy},
	journal = {J AAPOS},
	year = {2023},
	month = {2023 Jul 13},
	abstract = {BACKGROUND: Glaucoma secondary to familial exudative vitreoretinopathy presents as angle closure by either neovascular or non-neovascular mechanisms. We analyze the presentation and outcomes of two types of childhood glaucoma secondary to familial exudative vitreoretinopathy (FEVR). METHODS: This retrospective cross-sectional study included all patients \&lt;18 years of age diagnosed with glaucoma after or concurrently with a diagnosis of FEVR between 2010 and 2020 from Queen Sirikit National Institute of Child Health in Bangkok, Thailand. Two groups were analyzed: neovascular or non-neovascular angle-closure status. Primary outcome measures were final visual acuity and intraocular pressure (IOP) in both groups. RESULTS: Of 144 FEVR patients, 8 children (5.5\%; 11 eyes, 3 bilateral cases) developed childhood glaucoma. Mean time between FEVR presentation and glaucoma was 42.2 {\textpm} 40.0 months. In the neovascular group, 3 of 9 eyes presented with glaucoma at FEVR diagnosis; 3 of 9 eyes (33\%) required glaucoma surgery. In the non-neovascular group, 2 eyes presented with acute angle closure secondary to a phacomorphic lens. Both were treated with trabeculectomy, with resolution of pupillary block. All eyes had stage 4B FEVR or greater. Six of 8 eyes had stable or better visual acuity, and 10 eyes (91\%) had IOP \&lt;21 mm Hg at final follow-up. CONCLUSIONS: Childhood glaucoma secondary to FEVR is a rare complication caused by later stages of the disease. It may present as neovascular or non-neovascular angle closure, often requiring complex care. Therefore, awareness and adequate management of FEVR can help prevent additional morbidity from childhood glaucoma.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.05.006},
	author = {Seresirikachorn, Kasem and Thiamthat, Warakorn and Aramtiantamrong, Nattawadee and Traichaiyaporn, Sumalin and Wanichwecharungruang, Boonsong and Patel, Nimesh A and Vu, Daniel M}
}
@article {1589756,
	title = {Anterior versus posterior endoscopic cyclophotocoagulation: comparison of indications, populations, and outcomes},
	journal = {Int Ophthalmol},
	volume = {41},
	number = {9},
	year = {2021},
	month = {2021 Sep},
	pages = {3021-3028},
	abstract = {PURPOSE: To examine how indications, patient characteristics, and outcomes differ between anterior and posterior approaches of endoscopic cyclophotocoagulation (ECP) in the treatment of glaucoma. METHODS: This is a retrospective chart review of 9 anterior and 20 posterior ECP cases (n = 29). RESULTS: Posterior ECP cases were typically associated with a dramatic increase in intraocular pressure (IOP), whereas the anterior ECP was associated with chronically elevated pressures. The initial IOPs in mm Hg of posterior ECP cases (26.8 non-NVG; 35.2 NVG) were much greater than anterior ECP cases (17.8), and a greater overall reduction in IOP was observed in the posterior versus anterior ECP cases (10.3 posterior non-NVG; 21.3 posterior NVG; 3.6 anterior, P \&lt; .001). With procedural success defined as 6-month post-operative IOP falling within normal ranges and a decrease in either IOP or number of prescribed glaucoma medications, the success rate of ECP was 92\% for posterior NVG, 89\% for anterior and 75\% for posterior non-NVG cases (P = .34), similar to the previous literature. Of the four unsuccessful cases, two resulted in a normal IOP but lacked a drop in pressure or reduction in medication burden, one resulted in a 6-point drop in IOP but remained at 23\&nbsp;mm Hg, and one resulted in phthisis bulbi (3\%) from an initial pressure above 40\&nbsp;mm Hg. CONCLUSION: Endoscopic cyclophotocoagulation is an effective and safe procedure for severe glaucoma cases from both an anterior and posterior approach. Ophthalmologists should consider this procedure as part of their glaucoma treatment arsenal.},
	keywords = {Ciliary Body, Humans, Intraocular Pressure, Laser Coagulation, Retrospective Studies, Tonometry, Ocular, Treatment Outcome},
	issn = {1573-2630},
	doi = {10.1007/s10792-021-01863-5},
	author = {Seto, Brendan and Singh, Malkit K and Lemire, Colin A and Arroyo, Jorge G}
}
@article {1460377,
	title = {Effect of Scleral Lenses on Corneal Topography in Keratoconus: A Case Series of Cross-Linked Versus Non-Cross-Linked Eyes},
	journal = {Cornea},
	volume = {38},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {986-991},
	abstract = {PURPOSE: To evaluate the changes in anterior corneal topography induced by short-time wear of scleral contact lenses (SLs) in keratoconic subjects with and without a history of corneal cross-linking (CXL). METHODS: Nine keratoconic patients (14 eyes) were fitted with 18.5 mm SLs for optical rehabilitation. Subjects were divided into 2 groups: 7 eyes without a history of CXL (Non-CXL group) and 7 with a history of CXL (CXL group). Corneal topography was performed at baseline and after 2 and 5 hours of lens wear. The differences for simulated flat (Kflat), steep (Ksteep) and maximal (Kmax) corneal curvatures, central corneal astigmatism (CCA), and central cornea thickness were evaluated. RESULTS: No statistically significant difference was detected between Non-CXL and CXL groups in any of these measures. Statistically significant flattening was detected in Ksteep Repeated measures analysis of variance ([RM-ANOVA), F (2,24) = 11.32, P \&lt; 0.0001], CCA [RM-ANOVA, F (2,24) = 15.34, P \&lt; 0.0001], and Kmax [RM-ANOVA, F (2,24) = 19.10, P \&lt; 0.0001). From baseline to 5 hours of SL wear, Ksteep decreased on average from 53.1 to 52.4 D, Kmax decreased from 56.7 to 55.8 D, and CCA decreased from 7.2 to 6.3 D. Kmax showed a trend toward more flattening in the Non-CXL group. Central cornea thickness showed significant thickening over time from baseline (451 μm) to 5 hours (458 μm) of SL wear [RM-ANOVA, F (1,12) = 319.3, P \&lt; 0.0001]. CONCLUSIONS: Short-term scleral lens wear in keratoconic patients may cause flattening of the anterior cornea. A history of CXL treatment does not guarantee corneal shape stability after scleral lens wear. Practitioners should be aware of these changes because scleral lens wear may mask the signs of keratoconus progression.},
	keywords = {Adult, Collagen, Contact Lenses, Cornea, Corneal Stroma, Corneal Topography, Cross-Linking Reagents, Female, Humans, Keratoconus, Male, Photochemotherapy, Photosensitizing Agents, Riboflavin, Sclera, Visual Acuity, Young Adult},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002008},
	author = {Severinsky, Boris and Fadel, Daddi and Davelman, Jenya and Moulton, Eric}
}
@article {1333938,
	title = {Kinetics of corneal leukocytes by intravital multiphoton microscopy},
	journal = {FASEB J},
	volume = {33},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {2199-2211},
	abstract = {Corneal immune privilege is integral in maintaining the clear avascular window to the foreign world. The presence of distinct populations of corneal leukocytes (CLs) in the normal cornea has been firmly established. However, their precise function and kinetics remain, as of yet, unclear. Through intravital multiphoton microscopy (IV-MPM), allowing the means to accumulate critical spatial and temporal cellular information, we provide details for long-term investigation of CL morphology and kinetics under steady state and following inflammation. Significant alterations in size and morphology of corneal CD11c dendritic cells (DCs) were noted following acute sterile inflammation, including cell volume (4364.4 {\textpm} 489.6 vs. 1787.6 {\textpm} 111.0 μm, P \&lt; 0.001) and sphericity (0.82 {\textpm} 0.01 vs. 0.42 {\textpm} 0.02, P \&lt; 0.001) compared with steady state. Furthermore, IV-MPM analyses revealed alterations in both the CD11c DC and major histocompatibility complex class II (MHC)-II mature antigen-presenting cell population kinetics during inflammation, including track displacement length (CD11c: 16.57 {\textpm} 1.41 vs. 4.64 {\textpm} 0.56 μm, P \&lt; 0.001; MHC-II: 9.03 {\textpm} 0.37 vs. 4.09 {\textpm} 0.39, P \&lt; 0.001) and velocity (CD11c: 1.91 {\textpm} 0.07 μm/min vs. 1.73 {\textpm} 0.1302 μm/min; MHC-II: 2.97 {\textpm} 0.07 vs. 1.62 {\textpm} 0.08, P \&lt; 0.001) compared with steady state. Our results reveal in vivo evidence of sessile CL populations exhibiting dendritic morphology under steady state and increased velocity of spherical leukocytes following inflammation. IV-MPM represents a powerful tool to study leukocytes in corneal diseases in context.-Seyed-Razavi, Y., Lopez, M. J., Mantopoulos, D., Zheng, L., Massberg, S., Sendra, V. G., Harris, D. L., Hamrah, P. Kinetics of corneal leukocytes by intravital multiphoton microscopy.},
	issn = {1530-6860},
	doi = {10.1096/fj.201800684RR},
	author = {Seyed-Razavi, Yashar and Lopez, Maria J and Mantopoulos, Dimosthenis and Zheng, Lixin and Massberg, Steffen and Sendra, Victor G and Harris, Deshea L and Hamrah, Pedram}
}
@article {1367079,
	title = {Imaging appearance of the lateral rectus-superior rectus band in 100 consecutive patients without strabismus},
	journal = {AJNR Am J Neuroradiol},
	volume = {35},
	number = {9},
	year = {2014},
	pages = {1830-5},
	author = {Patel SH and Cunnane ME and Juliano AF and Vangel MG and Kazlas MA and Moonis G}
}
@article {1328902,
	title = {Genome-Wide Association Study Identifies a Susceptibility Locus for Comitant Esotropia and Suggests a Parent-of-Origin Effect},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {10},
	year = {2018},
	month = {2018 Aug 01},
	pages = {4054-4064},
	abstract = {Purpose: To identify genetic variants conferring susceptibility to esotropia. Esotropia is the most common form of comitant strabismus, has its highest incidence in European ancestry populations, and is believed to be inherited as a complex trait. Methods: White European American discovery cohorts with nonaccommodative (826 cases and 2991 controls) or accommodative (224 cases and 749 controls) esotropia were investigated. White European Australian and United Kingdom cohorts with nonaccommodative (689 cases and 1448 controls) or accommodative (66 cases and 264 controls) esotropia were tested for replication. We performed a genome-wide case-control association study using a mixed linear additive model. Meta-analyses of discovery and replication cohorts were then conducted. Results: A significant association with nonaccommodative esotropia was discovered (odds ratio [OR] = 1.41, P = 2.84 {\texttimes} 10-09) and replicated (OR = 1.23, P = 0.01) at rs2244352 [T] located within intron 1 of the WRB (tryptophan rich basic protein) gene on chromosome 21 (meta-analysis OR = 1.33, P = 9.58 {\texttimes} 10-11). This single nucleotide polymorphism (SNP) is differentially methylated, and there is a statistically significant skew toward paternal inheritance in the discovery cohort. Meta-analysis of the accommodative discovery and replication cohorts identified an association with rs912759 [T] (OR = 0.59, P = 1.89 {\texttimes} 10-08), an intergenic SNP on chromosome 1p31.1. Conclusions: This is the first genome-wide association study (GWAS) to identify significant associations in esotropia and suggests a parent-of-origin effect. Additional cohorts will permit replication and extension of these findings. Future studies of rs2244352 and WRB should provide insight into pathophysiological mechanisms underlying comitant strabismus.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-24082},
	author = {Shaaban, Sherin and MacKinnon, Sarah and Andrews, Caroline and Staffieri, Sandra E and Maconachie, Gail D E and Chan, Wai-Man and Whitman, Mary C and Morton, Sarah U and Yazar, Seyhan and Macgregor, Stuart and Elder, James E and Traboulsi, Elias I and Gottlob, Irene and Hewitt, Alex W and Strabismus Genetics Research Consortium and Hunter, David G and Mackey, David A and Engle, Elizabeth C}
}
@article {1363200,
	title = {RYR1 mutations as a cause of ophthalmoplegia, facial weakness, and malignant hyperthermia},
	journal = {JAMA Ophthalmol},
	volume = {131},
	number = {12},
	year = {2013},
	month = {2013 Dec},
	pages = {1532-40},
	abstract = {IMPORTANCE: Total ophthalmoplegia can result from ryanodine receptor 1 (RYR1) mutations without overt associated skeletal myopathy. Patients carrying RYR1 mutations are at high risk of developing malignant hyperthermia. Ophthalmologists should be familiar with these important clinical associations. OBJECTIVE: To determine the genetic cause of congenital ptosis, ophthalmoplegia, facial paralysis, and mild hypotonia segregating in 2 pedigrees diagnosed with atypical Moebius syndrome or congenital fibrosis of the extraocular muscles. DESIGN, SETTING, AND PARTICIPANTS: Clinical data including medical and family histories were collected at research laboratories at Boston Children{\textquoteright}s Hospital and Jules Stein Eye Institute (Engle and Demer labs) for affected and unaffected family members from 2 pedigrees in which patients presented with total ophthalmoplegia, facial weakness, and myopathy. INTERVENTION: Homozygosity mapping and whole-exome sequencing were conducted to identify causative mutations in affected family members. Histories, physical examinations, and clinical data were reviewed. MAIN OUTCOME AND MEASURE: Mutations in RYR1. RESULTS: Missense mutations resulting in 2 homozygous RYR1 amino acid substitutions (E989G and R3772W) and 2 compound heterozygous RYR1 substitutions (H283R and R3772W) were identified in a consanguineous and a nonconsanguineous pedigree, respectively. Orbital magnetic resonance imaging revealed marked hypoplasia of extraocular muscles and intraorbital cranial nerves. Skeletal muscle biopsy specimens revealed nonspecific myopathic changes. Clinically, the patients{\textquoteright} ophthalmoplegia and facial weakness were far more significant than their hypotonia and limb weakness and were accompanied by an unrecognized susceptibility to malignant hyperthermia. CONCLUSIONS AND RELEVANCE: Affected children presenting with severe congenital ophthalmoplegia and facial weakness in the setting of only mild skeletal myopathy harbored recessive mutations in RYR1, encoding the ryanodine receptor 1, and were susceptible to malignant hyperthermia. While ophthalmoplegia occurs rarely in RYR1-related myopathies, these children were atypical because they lacked significant weakness, respiratory insufficiency, or scoliosis. RYR1-associated myopathies should be included in the differential diagnosis of congenital ophthalmoplegia and facial weakness, even without clinical skeletal myopathy. These patients should also be considered susceptible to malignant hyperthermia, a life-threatening anesthetic complication avoidable if anticipated presurgically.},
	keywords = {Amino Acid Substitution, Blepharoptosis, Child, Consanguinity, Diseases in Twins, DNA Mutational Analysis, Exome, Eye Diseases, Hereditary, Female, Fibrosis, Genotype, Homozygote, Humans, Infant, Magnetic Resonance Imaging, Male, Malignant Hyperthermia, Mobius Syndrome, Mutation, Missense, Ophthalmoplegia, Pedigree, Ryanodine Receptor Calcium Release Channel, Twins, Dizygotic},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2013.4392},
	author = {Shaaban, Sherin and Ramos-Platt, Leigh and Gilles, Floyd H and Chan, Wai-Man and Andrews, Caroline and De Girolami, Umberto and Demer, Joseph and Engle, Elizabeth C}
}
@article {1782336,
	title = {Leber{\textquoteright}s Hereditary Optic Neuropathy in a Nonagenarian},
	journal = {J Neuroophthalmol},
	year = {2023},
	month = {2023 Nov 22},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000002040},
	author = {Shah, Madhura P and Chen, Amalie and Rizzo, Joseph F}
}
@article {1309953,
	title = {Technology-enabled examinations of cardiac rhythm, optic nerve, oral health, tympanic membrane, gait and coordination evaluated jointly with routine health screenings: an observational study at the 2015 Kumbh Mela in India},
	journal = {BMJ Open},
	volume = {8},
	number = {4},
	year = {2018},
	month = {2018 Apr 20},
	pages = {e018774},
	abstract = {OBJECTIVES: Technology-enabled non-invasive diagnostic screening (TES) using smartphones and other point-of-care medical devices was evaluated in conjunction with conventional routine health screenings for the primary care screening of patients. DESIGN: Dental conditions, cardiac ECG arrhythmias, tympanic membrane disorders, blood oxygenation levels, optic nerve disorders and neurological fitness were evaluated using FDA-approved advanced smartphone powered technologies. Routine health screenings were also conducted. A novel remote web platform was developed to allow expert physicians to examine TES data and compare efficacy with routine health screenings. SETTING: The study was conducted at a primary care centre during the 2015 Kumbh Mela in Maharashtra, India. PARTICIPANTS: 494 consenting 18-90 years old adults attending the 2015 Kumbh Mela were tested. RESULTS: TES and routine health screenings identified unique clinical conditions in distinct patients. Intraoral fluorescent imaging classified 63.3\% of the population with dental caries and periodontal diseases. An association between poor oral health and cardiovascular illnesses was also identified. Tympanic membrane imaging detected eardrum abnormalities in 13.0\% of the population, several with a medical history of hearing difficulties. Gait and coordination issues were discovered in eight subjects and one subject had arrhythmia. Cross-correlations were observed between low oxygen saturation and low body mass index (BMI) with smokers (p=0.0087 and p=0.0122, respectively), and high BMI was associated with elevated blood pressure in middle-aged subjects. CONCLUSIONS: TES synergistically identified clinically significant abnormalities in several subjects who otherwise presented as normal in routine health screenings. Physicians validated TES findings and used routine health screening data and medical history responses for comprehensive diagnoses for at-risk patients. TES identified high prevalence of oral diseases, hypertension, obesity and ophthalmic conditions among the middle-aged and elderly Indian population, calling for public health interventions.},
	issn = {2044-6055},
	doi = {10.1136/bmjopen-2017-018774},
	author = {Shah, Pratik and Yauney, Gregory and Gupta, Otkrist and Patalano Ii, Vincent and Mohit, Mrinal and Merchant, Rikin and Subramanian, S V}
}
@article {1667702,
	title = {EPIRETINAL MEMBRANE WITH FOVEAL HERNIATION: Visual and Surgical Outcomes},
	journal = {Retina},
	volume = {43},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {182-190},
	abstract = {PURPOSE: Foveal herniation occurs when neuroretinal tissue protrudes through and above the level of an epiretinal membrane. This study describes the visual symptoms and spectral domain optical coherence tomography findings associated with foveal herniation and evaluates the postoperative visual, anatomical, and surgical outcomes. METHODS: A multicenter retrospective review of patients diagnosed with epiretinal membrane identified 59 patients with preoperative foveal herniation on spectral domain optical coherence tomography. Data regarding visual symptoms, preoperative and postoperative best-corrected visual acuity (BCVA), central retinal thickness, macular volume, and size of foveal herniation were collected, and statistical analysis was performed. RESULTS: A total of 58 of the 59 patients with foveal herniation underwent surgical epiretinal membrane peeling, with foveal contour restored in 53.5\% of patients after surgery. Average BCVA improved from 20/80 to 20/40 Snellen equivalent at most-recent postoperative visit (P \&lt; 0.0001). The average central retinal thickness decreased from 632 {\textmu}m to 432 {\textmu}m (P \&lt; 0.0001) and the average macular volume decreased from 11.3 mm3 to 9.5 mm3 (P \&lt; 0.0001) at 3 months postoperatively. Preoperatively, greater herniation height was associated with worse BCVA (P = 0.008), greater central retinal thickness (P = 0.01), retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone abnormality, and external limiting membrane abnormalities (P \&lt; 0.05). Postoperatively, there was a decrease in retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone, and external limiting membrane abnormality (P \&lt; 0.05) on spectral domain optical coherence tomography. CONCLUSION: Patients with larger foveal herniation height had greater preoperative central retinal thickness, worse preoperative and postoperative BCVA, and more intraretinal abnormalities on spectral domain optical coherence tomography. Surgical epiretinal membrane peeling in patients with foveal herniation resulted in a significant improvement in patients{\textquoteright} BCVA and microstructural abnormalities.},
	keywords = {Epiretinal Membrane, Humans, Macular Edema, Retinoschisis, Retrospective Studies, Tomography, Optical Coherence, Treatment Outcome, Vitrectomy},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003669},
	author = {Shah, Saumya M and Eliott, Dean and Cox, Jacob T and Yonekawa, Yoshihiro and Mahmoudzadeh, Raziyeh and Peck, Travis J and Regillo, Carl D and Ho, Allen C and Oellers, Patrick and Choudhury, Mahin and Arboleda, Nathan and Gentile, Ronald C and Sun, Vincent and Iezzi, Raymond}
}
@article {314191,
	title = {Adjustable nasal transposition of split lateral rectus muscle for third nerve palsy},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {963-9},
	abstract = {IMPORTANCE: Third nerve palsy causes disfiguring, incomitant strabismus with limited options for correction. OBJECTIVE: To evaluate the oculomotor outcomes, anatomical changes, and complications associated with adjustable nasal transposition of the split lateral rectus (LR) muscle, a novel technique for managing strabismus associated with third nerve palsy. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review appraising outcomes of 6 consecutive patients with third nerve palsy who underwent adjustable nasal transposition of the split LR muscle between 2010 and 2012 with follow-up of 5 to 25 months at a tertiary referral center. INTERVENTION: Adjustable nasal transposition of the split LR muscle. MAIN OUTCOMES AND MEASURES: The primary outcome was postoperative horizontal and vertical alignment. Secondary outcomes were (1) appraising the utility of adjustable positioning, (2) demonstrating the resultant anatomical changes using magnetic resonance imaging, and (3) identifying associated complications. RESULTS: Four of 6 patients successfully underwent the procedure. Of these, 3 patients achieved orthotropia. Median preoperative horizontal deviation was 68 prism diopters of exotropia and median postoperative horizontal deviation was 0 prism diopters (P = .04). Two patients had preoperative vertical misalignment that resolved with surgery. All 4 patients underwent intraoperative adjustment of LR positioning. Imaging demonstrated nasal redirection of each half of the LR muscle around the posterior globe, avoiding contact with the optic nerve; the apex of the split sat posterior to the globe. One patient had transient choroidal effusion and undercorrection. Imaging revealed, in this case, the apex of the split in contact with the globe at an anterolateral location, suggesting an inadequate posterior extent of the split. In 2 patients, the surgical procedure was not completed because of an inability to nasally transpose a previously operated-on LR muscle. CONCLUSIONS AND RELEVANCE: Adjustable nasal transposition of the split LR muscle can achieve excellent oculomotor alignment in some cases of third nerve palsy. The adjustable modification allows optimization of horizontal and vertical alignment. Imaging confirms that the split LR muscle tethers the globe, rotating it toward primary position. Case selection is critical because severe LR contracture, extensive scarring from prior strabismus surgery, or inadequate splitting of the LR muscle may reduce the likelihood of success and increase the risk of sight-threatening complications. Considering this uncertainty, more experience is necessary before widespread adoption of this technique should be considered.},
	keywords = {Adult, Child, Female, Humans, Infant, Male, Middle Aged, Nose, Oculomotor Muscles, Oculomotor Nerve Diseases, Retrospective Studies},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.756},
	author = {Shah, Ankoor S and Prabhu, Sanjay P and Sadiq, Mohammad Ali A and Mantagos, Iason S and Hunter, David G and Dagi, Linda R}
}
@article {1677751,
	title = {Insights into the genotype-phenotype relationship of ocular manifestations in Kabuki syndrome},
	journal = {Am J Med Genet A},
	volume = {191},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {1325-1338},
	abstract = {We aim to assess if genotype-phenotype correlations are present within ocular manifestations of Kabuki syndrome (KS) among a large multicenter cohort.\&nbsp;We conducted a retrospective, medical record review including clinical history and comprehensive ophthalmological examinations of a total of 47 individuals with molecularly confirmed KS and ocular manifestations at Boston Children{\textquoteright}s Hospital and Cincinnati Children{\textquoteright}s Hospital Medical Center. We assessed information regarding ocular structural, functional, and adnexal elements as well as pertinent associated phenotypic features associated with KS. For both type 1 KS (KS1) and type 2 KS (KS2), we observed more severe eye pathology in nonsense variants towards the C-terminus of each gene, KMT2D and KDM6A, respectively. Furthermore, frameshift variants appeared to be not associated with structural ocular elements. Between both types of KS, ocular structural elements were more frequently identified in KS1 compared with KS2, which only involved the optic disc in our cohort. These results reinforce the need for a comprehensive ophthalmologic exam upon diagnosis of KS and regular follow-up exams. The specific genotype may allow risk stratification of the severity of the ophthalmologic manifestation. However, additional studies involving larger cohorts are needed to replicate our observations and conduct powered analyses to more formally risk-stratify based on genotype, highlighting the importance of multicenter collaborations in rare disease research.},
	keywords = {Abnormalities, Multiple, Genotype, Histone Demethylases, Humans, Mutation, Phenotype, Retrospective Studies, Vestibular Diseases},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.63155},
	author = {Shah, Suraj S and Fulton, Anne and Jabroun, Mireille and Brightman, Diana and Simpson, Brittany N and Bodamer, Olaf A}
}
@article {1626092,
	title = {Worldwide outcomes of nasal transposition of the split lateral rectus muscle for strabismus associated with 3rd-nerve palsy},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {5},
	year = {2023},
	month = {2023 May},
	pages = {725-731},
	abstract = {BACKGROUND/AIMS: To determine success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating strabismus from 3rd-nerve palsy. METHODS: An international, multicentre, registry of patients with unilateral 3rd-nerve palsy treated with NTSLR was created. Patients with concurrent surgery on the contralateral eye were excluded. Primary outcome was horizontal alignment within 15 prism dioptres (PD) of orthotropia. Incidence of technical difficulties and vision-threatening complications by 6 months post-procedure were reported. RESULTS: Ninety-eight patients met inclusion criteria. Median age was 33.5 years (IQR 10.75-46). Aetiologies included congenital (31\%), neoplastic (16\%) and traumatic (15\%). Twenty-five per cent of patients had prior ipsilateral strabismus surgery. Median exotropia decreased from 70PD preoperatively (IQR 50-90) to 1PD postoperatively (IQR 0-15.5), with a success rate of 69\%. Performing concurrent superior oblique muscle tenotomy (SOT) was independently associated with success (p=0.001). Technical challenges occurred in 30\% of cases, independently associated with a history of ipsilateral strabismus surgery (p=0.01). Eleven per cent of patients had vision-threatening complications, independently associated with more posterior placement of the split lateral rectus (LR) muscle (p\&lt;0.001), and most commonly transient serous choroidal effusion. Surgical placement of the split LR muscle within 4.25 mm of the medial rectus (MR) muscle insertion reduced this risk. CONCLUSION: NTSLR significantly improved primary position alignment altered by 3rd-nerve palsy. Concurrent SOT and placement of the split LR muscle <=4.25 mm posterior to the MR muscle insertion optimised outcomes. NTSLR proved technically challenging when prior ipsilateral strabismus surgery had been performed.},
	keywords = {Adult, Exotropia, Humans, Oculomotor Muscles, Oculomotor Nerve Diseases, Ophthalmologic Surgical Procedures, Paralysis, Retrospective Studies, Strabismus, Treatment Outcome, Vision, Binocular},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-319667},
	author = {Shah, Ankoor S and Ugo Dodd, Mary-Magdalene and Gokyigit, Birsen and Lorenz, Birgit and Laurent, Erick and Sadiq, Mohammad Ali Ayaz and Tsai, Chong-Bin and Gravier, Nicolas and Goberville, Mitra and Basiakos, Sotirios and Zurakowski, David and Dagi, Linda R and NTSLR3NP Study Group}
}
@article {1619412,
	title = {Use of Teleophthalmology for Evaluation of Ophthalmic Emergencies by Ophthalmology Residents in the Emergency Department},
	journal = {Telemed J E Health},
	volume = {28},
	number = {6},
	year = {2022},
	month = {2022 Jun},
	pages = {858-864},
	abstract = {Background: Utilizing telemedicine is one approach to reduce the ever-increasing burden of patients on emergency departments (EDs) and consulting physicians. Utilization of telemedicine services in the ED may also benefit resident education. Materials and Methods: Ten first-year ophthalmology residents were trained to use a Topcon 3D Optical Coherence Tomography (OCT)-1 Maestro to capture OCT images and fundus photos in patients presenting to the ED with urgent ophthalmic concerns. Findings were communicated to the supervising ophthalmologist. Retrospective chart review was conducted to obtain patient characteristics and final ophthalmologist diagnosis. Residents rated ease of use, technical reliability, and educational value through a survey. Results: From December 1, 2019, to December 1, 2020, the device was used in 109 patient encounters, capturing 887 images (average 8.1 images per encounter). Patients on whom the device was used were on average 48.5 years old ({\textpm}17.2, range 17-90) and 59.6\% were female. The imaging device was utilized most commonly for evaluating papilledema (n = 21, 18.6\%), new-onset visual acuity/visual field defects (n = 12, 10.6\%), retinal detachment/tear (n = 8, 7.1\%), and ophthalmic trauma workup (n = 8, 7.1\%). Eight residents completed the survey and most (n = 7) agreed or strongly agreed that the device helped them diagnose patients more accurately. Technical issues such as machine malfunction, image artifacts, and problems syncing with the electronic health record and computer were noted by survey respondents. Conclusions: The most common use of teleophthalmology in the ED setting was evaluation of papilledema; the majority of residents perceived an educational benefit from this tool. Efforts should be made to address the technical challenges to increase the utility of this device.},
	keywords = {Emergencies, Emergency Service, Hospital, Female, Humans, Male, Middle Aged, Ophthalmology, Papilledema, Reproducibility of Results, Retrospective Studies, Telemedicine},
	issn = {1556-3669},
	doi = {10.1089/tmj.2021.0334},
	author = {Shah, Yesha S and Fliotsos, Michael J and Alaqeel, Abdulaziz and Boland, Michael V and Zafar, Sidra and Srikumaran, Divya and Woreta, Fasika A}
}
@article {1363201,
	title = {Trends in female representation in published ophthalmology literature, 2000-2009},
	journal = {Digit J Ophthalmol},
	volume = {19},
	number = {4},
	year = {2013},
	month = {2013},
	pages = {50-5},
	abstract = {PURPOSE: To examine trends in female first and last authors in clinical ophthalmology literature published from January 2000 to December 2009. METHODS: A total of 3760 articles in American Journal of Ophthalmology (AJO), 2347 articles in Archives of Ophthalmology (Archives), and 3838 articles in Ophthalmology spanning 10 years of published ophthalmology peer-reviewed literature were examined. All original research articles and brief reports indexed online were included. Author gender was determined by an exhaustive Internet search. Articles were excluded if the sex of the author could not be determined or was not applicable (for example, articles by a study group rather than an individual author). RESULTS: Gender information was identified in 86.8\% of articles for first authors and 86\% for last authors. The number of female first authors (P \&lt; 0.0001) and last authors (P = 0.005) increased significantly in the study period in all journals examined, with a significant association between the sex of the first and last authors (OR = 2.19; 95\% CI, 1.96-2.46; P \&lt; 0.0001), when examining all articles. Female representation increased for last authors significantly only in Ophthalmology. There was a significant correlation between gender of the first author and total number of authors that was not observed with last-author sex. CONCLUSIONS: Female first authorship has increased from 2000 to 2009 and is correlated with the gender of the last author; however, there were fewer female last authors compared to female first authors in the same period.},
	keywords = {Authorship, Female, Humans, Ophthalmology, Periodicals as Topic, Publishing, Sex Distribution},
	issn = {1542-8958},
	doi = {10.5693/djo.01.2013.07.002},
	author = {Shah, Deepika N and Huang, Jiayan and Ying, Gui-Shuang and Pietrobon, Ricardo and O{\textquoteright}Brien, Joan M}
}
@article {1782441,
	title = {Risk factors associated with cystoid macular edema amongst patients undergoing primary repair of rhegmatogenous retinal detachment},
	journal = {Ophthalmol Retina},
	year = {2023},
	month = {2023 Nov 28},
	abstract = {PURPOSE: To investigate predictors of the development and resolution of cystoid macular edema (CME) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective cross-sectional study SUBJECTS: Patients who underwent primary repair of uncomplicated RRD. METHODS: Demographics, ophthalmologic history, visual acuity, RRD features, time to development/resolution of CME, OCT characteristics of CME/ERM, type of surgery, and treatments were collected. Logistic regressions were used to identify predictors of CME development and resolution. MAIN OUTCOME MEASURES: Predictors of CME development and resolution. RESULTS: A total of 708 eyes were included, of which 55 (7.8\%) developed CME. Factors associated with an increased risk of CME development included total number of retinal detachment surgeries (OR 1.66 [1.24 - 2.23], p \&lt;0.001), prior intraocular surgery (OR 4.43 [1.19-16.51], p=0.03) and presence of ERM after surgery (OR 4.49[2.30-8.74], p \&lt;0.001). Patients undergoing PPV were more likely to develop CME compared to patients undergoing SB (OR 3.09 [1.18, 8.10], p = 0.02). A longer average time to CME detection was associated with lower CME resolution (OR 0.94 [0.89-0.998], p=0.04). In patients who developed an ERM post-surgically, those who developed CME after ERM had a lower rate of resolution compared to those who developed CME before ERM (p=0.03). CONCLUSIONS: CME may be more likely to develop in patients undergoing PPV than SB, those who underwent more surgeries for RRD repair, those who had prior intraocular surgery, or those who developed an ERM after RRD repair. Resolution of CME may be affected by the time to detection of CME and ERM development.},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.11.013},
	author = {Shah, Yesha S and Abidi, Muhammad and Ahmed, Ishrat and Arsiwala-Scheppach, Lubaina T and Ong, Sally S and Wu, David and Handa, James T}
}
@article {1522723,
	title = {Exudative Retinal Detachment in Ocular Inflammatory Diseases: Risk and Predictive Factors},
	journal = {Am J Ophthalmol},
	volume = {218},
	year = {2020},
	month = {2020 Oct},
	pages = {279-287},
	abstract = {PURPOSE: This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases. DESIGN: Retrospective cohort study. METHODS: Patients with noninfectious ocular inflammation had been followed longitudinally between 1978 and 2007 at 4\&nbsp;US subspecialty uveitis centers. The main outcome measurements were occurrences of ERD and predictive factors. RESULTS: A total of 176 of 14,612 eyes with ocular inflammation presented with ERD. Among uveitis cases, Vogt-Koyanagi-Harada syndrome (VKH) (odds ratio [OR]\&nbsp;= 109), undifferentiated choroiditis (OR\&nbsp;= 9.18), sympathetic ophthalmia (OR\&nbsp;= 8.43), primary or secondary panuveitis (OR\&nbsp;= 7.09), multifocal choroiditis with panuveitis (OR\&nbsp;= 4.51), and "other" forms of posterior uveitis (OR\&nbsp;= 16.9) were associated with a higher prevalence of ERD. Among the 9,209 uveitic or scleritic eyes initially free of ERD and followed, 137 incident ERD cases were observed over 28,949 eye-years at risk (incidence rate\&nbsp;= 0.47\% [0.40\%-0.56\%/eye-year]). VKH (HR\&nbsp;= 13.2), sympathetic ophthalmia (HR\&nbsp;= 5.82), undifferentiated choroiditis (HR\&nbsp;= 6.03), primary or secondary panuveitis (HR\&nbsp;= 4.21), and rheumatoid arthritis (HR\&nbsp;= 3.30) were significantly associated with incident ERD. A significant dose-response relationship with the prevalence and incidence of ERD were observed for AC cells and vitreous cell activity. African Americans had significantly higher prevalence and incidence of ERD. CONCLUSIONS: Other ocular inflammatory conditions in addition to VKH syndrome and posterior scleritis were associated with increased risk of ERD, indicating that ERD does not necessarily dictate a diagnosis of VKH or posterior scleritis. In addition, the relationship between ERD and inflammatory severity factors implies that inflammation is a key predictive factor associated with developing ERD and requires early and vigorous control.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.06.019},
	author = {Shah, Deepika N and Al-Moujahed, Ahmad and Newcomb, Craig W and Ka{\c c}maz, R Oktay and Daniel, Ebenezer and Thorne, Jennifer E and Foster, C Stephen and Jabs, Douglas A and Levy-Clarke, Grace A and Nussenblatt, Robert B and Rosenbaum, James T and Sen, H Nida and Suhler, Eric B and Bhatt, Nirali P and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases Research Group}
}
@article {1732511,
	title = {Retinal Physicians{\textquoteright} Views on Artificial Intelligence Adoption},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1017-1019},
	keywords = {Artificial Intelligence, Humans, Retina},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.07.017},
	author = {Shaheen, Abdulla R and Cai, Louis and Henderson, Harper and Patel, Nimesh A and Yannuzzi, Nicolas A}
}
@article {935686,
	title = {The Efficacy and Safety Profile of Ocriplasmin in Vitreomacular Interface Disorders.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	pages = {52-55},
	abstract = {Vitreomacular adhesion (VMA) describes the adhesion of the posterior hyaloid face to the inner retina in any part of the macula. This can arise after incomplete separation of the posterior vitreous cortex from the macula during vitreous liquefaction. While the VMA may resolve spontaneously, a strong and persistent adhesion can lead to a variety of anatomical changes, including vitreomacular traction (VMT) and macular hole (MH). Both conditions can present with metamorphopsia and decreased vision. In cases of symptomatic VMT and full-thickness macular hole, pars plana vitrectomy has long been the standard of care. However, due to the possible surgical complications and need for postoperative care, many have searched for non-surgical options via pharmacologic vitreolysis. Ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) is a recombinant protease approved in October 2012 for the treatment of symptomatic vitreomacular adhesion (VMA). There have been conflicting views on the safety of Ocriplasmin with changes in the ellipsoid zone seen on OCT and changes seen on ERG indicating photoreceptor damage. This publication reviews the efficacy and safety of ocriplasmin injection for VMA based on previously published data.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228416},
	author = {Shaikh, Mehrine and Miller, John B and Papakostas, Thanos D and Husain, Deeba}
}
@article {397866,
	title = {Mutations in Pneumococcal cpsE Generated via In Vitro Serial Passaging Reveal a Potential Mechanism of Reduced Encapsulation Utilized by a Conjunctival Isolate.},
	journal = {J Bacteriol},
	volume = {197},
	number = {10},
	year = {2015},
	month = {2015 May 15},
	pages = {1781-91},
	abstract = {UNLABELLED: The polysaccharide capsule of Streptococcus pneumoniae is required for nasopharyngeal colonization and for invasive disease in the lungs, blood, and meninges. In contrast, the vast majority of conjunctival isolates are acapsular. The first serotype-specific gene in the capsule operon, cpsE, encodes the initiating glycosyltransferase and is one of the few serotype-specific genes that can tolerate null mutations. This report characterizes a spontaneously arising TIGR4 mutant exhibiting a reduced capsule, caused by a 6-nucleotide duplication in cpsE which results in duplication of Ala and Ile at positions 45 and 46. This strain (AI45dup) possessed more exposed phosphorylcholine and was hypersusceptible to C3 complement deposition compared to the wild type. Accordingly, the mutant was significantly better at forming abiotic biofilms and binding epithelial cells in vitro but was avirulent in a sepsis model. In vitro serial passaging of the wild-type strain failed to reproduce the AI45dup mutation but instead led to a variety of mutants with reduced capsule harboring single nucleotide polymorphisms (SNPs) in cpsE. A single passage in the sepsis model after high-dose inoculation readily yielded revertants of AI45dup with restored wild-type capsule level, but the majority of SNP alleles of cpsE could not revert, suppress, or bypass. Analysis of cpsE in conjunctival isolates revealed a strain with a single missense mutation at amino acid position 377, which was responsible for reduced encapsulation. This study supports the hypothesis that spontaneous, nonreverting mutations in cpsE serve as a form of adaptive mutation by providing a selective advantage to S. pneumoniae in niches where expression of capsule is detrimental. IMPORTANCE: While the capsule of Streptococcus pneumoniae is required for colonization and invasive disease, most conjunctival isolates are acapsular by virtue of deletion of the entire capsular operon. We show that spontaneous acapsular mutants isolated in vitro harbor mostly nonrevertible single nucleotide polymorphism (SNP) null mutations in cpsE, encoding the initiating glycosyltransferase. From a small collection of acapsular conjunctival isolates, we identified one strain with a complete capsular operon but containing a SNP in cpsE that we show is responsible for the acapsular phenotype. We propose that acapsular conjunctival isolates may arise initially from such nonreverting SNP null mutations in cpsE, which can be followed later by deletion of portions or all of the cps operon.},
	issn = {1098-5530},
	doi = {10.1128/JB.02602-14},
	author = {Shainheit, Mara G and Valentino, Michael D and Gilmore, Michael S and Camilli, Andrew}
}
@article {1474218,
	title = {Vision Parameters Most Important to Functionality in Glaucoma},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {14},
	year = {2019},
	month = {2019 Nov 01},
	pages = {4556-4563},
	abstract = {Purpose: To determine the importance of various vision parameters to functionality in glaucoma. Methods: Vision was measured using seven parameters: visual acuity (VA), contrast sensitivity (CS), integrated visual field (IVF), area under the log CS function (AULCSF), color vision, stereoacuity, and VA with noise (ViN). Likelihood ratio testing (LRT) determined if the full set of visual parameters significantly explained variability in 10 functional outcomes. For outcomes where the visual contribution was significant, dominance analysis determined the relative importance of the various visual parameters. Results: The analysis included 151 glaucoma patients. Mean age was 70 {\textpm} 6.8 years, and 47\% were men. Significant visual contributions (LRT P \&lt; 0.05) were noted for glaucoma quality of life (GQL-15), reading speed, driving cessation, daily steps, and base of support while walking, but not for fear of falling, balance, gait velocity, stride velocity, and stride length while walking (LRT P \&gt; 0.05). The most important parameter (and percent contribution) to vision-explained variability were AULCSF for daily steps (45\%), IVF for base of support (35\%), VA for reading speed (34\%), CS for GQL-15 (30\%), and VA for driving cessation (26\%). Conclusions: Measures of visual ability are important for several aspects of quality of life and functionality. The most important vision parameter for functionality differs depending on the domain studied. Reading and driving were explained by VA and IVF sensitivity. On the other hand, GQL-15 and daily steps were more heavily influenced by CS and AULCSF, which are rarely performed clinically.},
	issn = {1552-5783},
	doi = {10.1167/iovs.19-28023},
	author = {Shakarchi, Ahmed F and Mihailovic, Aleksandra and West, Sheila K and Friedman, David S and Ramulu, Pradeep Y}
}
@article {1474195,
	title = {RNA Splicing Factor Mutations That Cause Retinitis Pigmentosa Result in Circadian Dysregulation},
	journal = {J Biol Rhythms},
	volume = {35},
	number = {1},
	year = {2020},
	month = {2020 Feb},
	pages = {72-83},
	abstract = {Circadian clocks regulate multiple physiological processes in the eye, but their requirement for retinal health remains unclear. We previously showed that Drosophila homologs of spliceosome proteins implicated in human retinitis pigmentosa (RP), the most common genetically inherited cause of blindness, have a role in the brain circadian clock. In this study, we report circadian phenotypes in murine models of RP. We found that mice carrying a homozygous H2309P mutation in () display a lengthened period of the circadian wheel-running activity rhythm. We show also that the daily cycling of circadian gene expression is dampened in the retina of H2309P mice. Surprisingly, molecular rhythms are intact in the eye cup, which includes the retinal pigment epithelium (RPE), even though the RPE is thought to be the primary tissue affected in this form of RP. Downregulation of , another RNA splicing factor implicated in RP, leads to period lengthening in a human cell culture model. The period of circadian bioluminescence in primary fibroblasts of human RP patients is not significantly altered. Together, these studies link a prominent retinal disorder to circadian deficits, which could contribute to disease pathology.},
	issn = {1552-4531},
	doi = {10.1177/0748730419887876},
	author = {Shakhmantsir, Iryna and Dooley, Scott J and Kishore, Siddharth and Chen, Dechun and Pierce, Eric and Bennett, Jean and Sehgal, Amita}
}
@article {1460385,
	title = {Surgical management of acquired implantation iris cysts: indications, surgical challenges and outcomes},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {1179-1183},
	abstract = {PURPOSE: To describe the clinical spectrum, clinicopathological correlation and outcomes of different surgical strategies in the management of acquired implantation iris cysts. METHODS: From 1 January 1989 to 31 December 2015, 27 patients (27 eyes) with acquired implantation iris cysts underwent surgery. The charts were reviewed for demographics, preoperative characteristics, surgical approach, histopathological records of excised cyst and postoperative outcomes. RESULTS: The median age at presentation was 5 years (IQR: 1.3-14 years). Out of 27 patients, 21 (78\%) were aged<=18 years. Almost two-third (17/27, 63\%) patients had history of penetrating ocular trauma prior to surgery. All patients underwent cyst aspiration combined with complete cyst excision with additional surgical procedures when necessary. Along with complete cyst excision, sector iridectomy was performed in 20/27 (74\%) eyes. At a median postoperative follow-up period of 8 months (range: 1-72 months), recurrence was noted in 3/27 (11\%) cases at a mean follow-up period of 2.3{\textpm}1.5 months postsurgery. Eyes in which sector iridectomy was performed had lower incidence of recurrence, and this was statistically significant (p=0.03). However, the improvement in best-corrected visual acuity postoperatively was not statistically significant (p=0.15). CONCLUSION: Acquired implantation iris cysts are associated with significant ocular morbidity. Complete excision of the cyst with sector iridectomy is an effective treatment option if other less invasive surgical approaches fail. Visual acuity can be significantly improved but is typically limited due to associated comorbidities.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-312738},
	author = {Shanbhag, Swapna S and Ramappa, Muralidhar and Chaurasia, Sunita and Murthy, Somasheila I}
}
@article {1498245,
	title = {Long-term outcomes of amniotic membrane treatment in acute Stevens-Johnson syndrome/toxic epidermal necrolysis},
	journal = {Ocul Surf},
	volume = {18},
	number = {3},
	year = {2020},
	month = {2020 07},
	pages = {517-522},
	abstract = {PURPOSE: To report the long-term outcomes of amniotic membrane (AM) use in the form of transplantation (AMT) and self-retained amniotic membrane (ProKera{\textregistered} device, PD) in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Electronic records of all patients with a diagnosis of SJS/TEN at Massachusetts Eye and Ear between January 2008 and January 2018 were reviewed. Patients who received AM in acute SJS/TEN were selected. Only patients with follow-up >= 3 months after discharge were included. RESULTS: Data of 55 eyes of 29 patients were analyzed. All 55 eyes received the first AM at a median interval of 5 days (inter-quartile range (IQR): 3-7 days) after onset of skin rash. Fifty-six percent of eyes (31/55) received AMT while 44\% (24/55) received PD. Forty percent of eyes (22/55) required a repeat AMT or PD. Median follow-up after initial AM was 2.5 years (IQR: 1.2-3.6 years). At last follow-up, the best-corrected visual acuity was >=20/40 in 87\% of eyes (48/55). The most common complications in the chronic phase were meibomian gland disease and dry eye, seen in 78\% of eyes (43/55) and 58\% of eyes (32/55) respectively. CONCLUSIONS: Long-term results show that early use of AM in the acute phase of SJS/TEN may be effective in mitigating severe vision loss after SJS/TEN. However, eyelid-related complications and dry eye remain a common problem even with the use of AM.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.03.004},
	author = {Shanbhag, Swapna S and Hall, Leangelo and Chodosh, James and Saeed, Hajirah N}
}
@article {1430538,
	title = {Sutureless amniotic membrane transplantation with cyanoacrylate glue for acute Stevens-Johnson syndrome/toxic epidermal necrolysis},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Mar 11},
	abstract = {Amniotic membrane (AM) transplantation, when performed in the acute phase in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) for patients with ocular complications, is known to reduce the morbidity of ocular complications in the chronic phase. In conditions such as SJS/TEN, AM needs to be secured to the ocular surface as well as the eyelids. Previously, techniques of securing a large sheet of AM with fibrin glue to the ocular surface and with sutures and bolsters to the eyelids have been described in the acute phase of SJS/TEN. These techniques often necessitate the use of an operating room in acutely ill patients. We describe a bedside technique that uses cyanoacrylate glue to secure the AM to the eyelids, as well as long-term outcomes in 4 patients with acute SJS/TEN. The combination of a custom symblepharon ring to secure AM over the entire ocular surface and cyanoacrylate glue to secure AM to the eyelid margins is quick, painless, does not require local or general anesthesia, and might prove useful in other conditions previously shown to benefit from AMT, such as ocular chemical injuries.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.03.001},
	author = {Shanbhag, Swapna S and Chodosh, James and Saeed, Hajirah N}
}
@article {1586194,
	title = {Diphtheroids as Corneal Pathogens in Chronic Ocular Surface Disease in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis},
	journal = {Cornea},
	volume = {40},
	number = {6},
	year = {2021},
	month = {2021 06 01},
	pages = {774-779},
	abstract = {PURPOSE: To characterize diphtheroid corneal infections in eyes in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Observational case series. RESULTS: Four eyes of 3 patients were included in this review. Each eye presented with persistent corneal epithelial defect with corneal thinning in the chronic phase of SJS/TEN. None of the epithelial defects were associated with stromal infiltration. The corneas were cultured at the time of workup of persistent epithelial defect (3 eyes) or at time of tectonic penetrating keratoplasty after perforation (1 eye). Cultures yielded abundant growth of Corynebacterium spp., including Corynebacterium jeikeium (n = 2), Corynebacterium glucuronolyticum (n = 1), and a multidrug-resistant Corynebacterium striatum isolate (n = 1). The ocular surface was stabilized with surgical intervention (1 eye) or with introduction of fortified topical antibiotic based on laboratory identification and susceptibility testing of the isolated organisms (3 eyes). Numerous risk factors for microbial keratitis were present in all 4 eyes. CONCLUSIONS: In eyes with a persistent corneal epithelial defect in the chronic phase of SJS/TEN, even in the absence of an infiltrate, corneal culture should be undertaken. Recognition and treatment of Corynebacterium spp. as opportunistic pathogens may lead to favorable outcomes in cases of clinically sterile ulceration during the chronic phase of SJS/TEN.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002696},
	author = {Shanbhag, Swapna S and Shih, Grace and Bispo, Paulo J M and Chodosh, James and Jacobs, Deborah S and Saeed, Hajirah N}
}
@article {1263401,
	title = {Keratolimbal allograft for limbal stem cell deficiency after severe corneal chemical injury: a systematic review},
	journal = {Br J Ophthalmol},
	volume = {102},
	number = {8},
	year = {2018},
	month = {2018 Aug},
	pages = {1114-1121},
	abstract = {PURPOSE: To review the published literature on outcomes of keratolimbal allograft (KLAL) for the surgical treatment of limbal stem cell deficiency (LSCD) and corneal blindness after severe corneal chemical injury. METHODS: Literature searches were conducted in the following electronic databases: MEDLINE, EMBASE, Science Citation Index, CINAHL, LILACS and the Cochrane Library. Standard systematic review methodology was applied. The main outcome measure was the proportion of eyes with best-corrected visual acuity (BCVA) >=20/200 at last follow-up. Other measures of allograft success were also collected. RESULTS: We identified six reports in which KLAL outcomes in the eyes after chemical injury could be distinguished. There were no randomised controlled studies. The outcomes of KLAL in 36 eyes of 33 patients were analysed. One study with seven eyes did not specify KLAL follow-up specific to chemical injury. Median postoperative follow-up for the other 29 eyes in 26 patients was 42 months (range 6.2-114 months). In the same 29 eyes, 69\% (20/29) had BCVA >=20/200 at the last follow-up examination. Eighty-nine per cent of all eyes (32/36) underwent penetrating keratoplasty simultaneous or subsequent to KLAL. CONCLUSIONS: The number of studies where outcomes of KLAL in eyes with severe corneal chemical injury could be discerned was limited, and variability was observed in outcome reporting. The quality of evidence to support the use of KLAL in LSCD in severe chemical corneal burns was low. Standardisation and longer follow-up are needed to better define evidence-based best practice when contemplating surgical intervention for blindness after corneal chemical injury. PROSPERO REGISTRATION NUMBER: CRD42017054733.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2017-311249},
	author = {Shanbhag, Swapna S and Saeed, Hajirah N and Paschalis, Eleftherios I and Chodosh, James}
}
@article {1452955,
	title = {Long-Term Effect of a Treatment Protocol for Acute Ocular Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis},
	journal = {Am J Ophthalmol},
	volume = {208},
	year = {2019},
	month = {2019 Dec},
	pages = {331-341},
	abstract = {PURPOSE: To describe the long-term effect of a treatment protocol for ocular involvement in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), including focused ocular examination and pathology-appropriate use of lubrication, topical corticosteroids, topical antibiotics, and amniotic membrane transplantation (AMT). DESIGN: Retrospective, comparative case series. METHODS: A total of 48 patients (96 eyes) were included in this study. Nine of 48 patients (18 eyes) had acute SJS/TEN from 2000 to 2007 and did not receive protocol care (Group I). Thirty-nine of 48 patients (78 eyes) had acute SJS/TEN from 2008 to 2017 and received protocol care (Group II). The main outcome measures were best-corrected visual acuity (BCVA) at final follow-up visit and incidence of complications in the chronic phase. RESULTS: No eyes in Group I received AMT for SJS/TEN, compared to 87\% of qualifying eyes in Group II (P \&lt; .0001) There was a significant difference in the proportion of eyes with BCVA >=20/40 at last follow-up between Group I and Group II (33\% vs 92\%, P\&nbsp;\&lt;\&nbsp;.001). The proportion of eyes with vision-threatening complications in the chronic phase was significantly higher in Group I versus Group II (67\% vs 17\%, P\&nbsp;= .002), with most complications occurring in the first 2 years after disease onset in both groups. CONCLUSIONS: A specific protocol for acute ocular care in SJS/TEN, including aggressive use of AMT, was highly successful in reducing corneal blindness and severe vision-threatening complications of the disorder.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.07.006},
	author = {Shanbhag, Swapna S and Rashad, Ramy and Chodosh, James and Saeed, Hajirah N}
}
@article {1658686,
	title = {Visual function and quality of life in patients with Stevens-Johnson syndrome who received acute protocol-based ocular care},
	journal = {Front Toxicol},
	volume = {4},
	year = {2022},
	month = {2022},
	pages = {992696},
	abstract = {Purpose: To report visual function and quality of life (VF/QOL) using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the ocular surface disease index (OSDI) in patients in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods: The NEI-VFQ-25 questionnaire was administered to 15 patients who received protocol-based care in the form of topical medications with or without amniotic membrane transplantation (AMT) for acute SJS/TEN. The scores obtained were compared with scores from a healthy population. The associations between the NEI-VFQ-25 and dry eye symptoms as measured by OSDI questionnaire were also studied. Results: Patients were surveyed at a mean of 4.47 {\textpm} 2.22 years after acute SJS/TEN. Eleven patients received AMT in the acute phase. The median best corrected visual acuity at the time of administration of the questionnaire was 20/20. The mean composite NEI-VFQ-25 score was 86.48 {\textpm} 12. Patients who received protocol-based treatment in the acute phase of SJS/TEN had comparable NEI-VFQ-25 scores with healthy subjects on all subscales except ocular pain (p = 0.027) and mental health (p = 0.014), which were significantly reduced. The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.75, p = 0.001). Conclusion: A protocol-based management strategy composed of early ophthalmic evaluation, grading based on severity, the use of topical corticosteroids and AMT in the acute phase of SJS/TEN in patients with ocular complications helped preserve the VF/QOL. This study highlights the impact of appropriate management of the ocular complications in the acute phase of SJS/TEN.},
	issn = {2673-3080},
	doi = {10.3389/ftox.2022.992696},
	author = {Shanbhag, Swapna S and Tahboub, Mohammad A and Chodosh, James and Saeed, Hajirah N}
}
@article {1333934,
	title = {Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival},
	journal = {Transplantation},
	volume = {103},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {182-190},
	abstract = {BACKGROUND: Regulatory T (Treg) cell-based immunotherapies have been studied as potential cell-based modalities for promoting transplant survival. However, the efficacy of local delivery of Treg cells in corneal transplantation has not been fully elucidated. Herein, we investigated the kinetics of migration of subconjunctivally injected Treg cells and their role in promoting corneal allograft survival. METHODS: GFPCD4CD25Foxp3 Treg cells were isolated from draining lymph nodes (DLNs) of GFP transgenic mice and were subconjunctivally injected to corneal allograft recipients. Next, Treg cells, conventional T cells (Tconv) or a combination of both was locally injected to graft recipients, and graft survival was determined by evaluating opacity scores for 10 weeks. Transplanted mice without treatment served as controls. The frequencies of major histocompatibility complex-IICD11b antigen-presenting cells, IFNγCD4 Th1 cells, and CD45 cells in the DLNs and cornea were evaluated at week 2 posttransplantation using flow cytometry. Expressions of IFNγ, IL-10 and TGF-β in the grafts were assessed using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: GFP Treg cells were detected in the ipsilateral cornea and DLNs of recipients 6 hours after injection. Subconjunctival injection of Treg cells significantly decreased the frequencies of mature antigen-presenting cells in the graft and DLNs, suppressed Th1 frequencies in DLNs, and inhibited CD45 cell infiltration to the graft. Finally, locally delivered Treg cells significantly reduced the expression of IFN-γ, enhanced the levels of IL-10 and TGF-β in the graft, and promoted long-term allograft survival. CONCLUSIONS: Our study elucidates the kinetics of migration of locally delivered Treg cells and shows their role in suppressing host immune response against the allograft.},
	issn = {1534-6080},
	doi = {10.1097/TP.0000000000002442},
	author = {Shao, Chunyi and Chen, Yihe and Nakao, Takeshi and Amouzegar, Afsaneh and Yin, Jia and Tahvildari, Maryam and Lu{\v z}nik, Zala and Chauhan, Sunil K and Dana, Reza}
}
@article {1351187,
	title = {Cytochrome P450 2C8 ω3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report},
	journal = {Arterioscler Thromb Vasc Biol},
	volume = {34},
	number = {3},
	year = {2014},
	month = {2014 Mar},
	pages = {581-6},
	abstract = {OBJECTIVE: Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. APPROACH AND RESULTS: The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a ω3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both ω3LCPUFA and ω6LCPUFA and antiangiogenic role of sEH in ω3LCPUFA metabolism were corroborated in aortic ring assays. CONCLUSIONS: Our results suggest that CYP2C ω3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization.},
	keywords = {Animals, Arachidonic Acid, Aryl Hydrocarbon Hydroxylases, Biotransformation, Cell Hypoxia, Cytochrome P-450 CYP2C8, Dietary Fats, Docosahexaenoic Acids, Eicosapentaenoic Acid, Epoxide Hydrolases, Eye Proteins, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Humans, Lipoxygenase, Macrophages, Mice, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Oxygen, Prostaglandin-Endoperoxide Synthases, Receptor, TIE-2, Recombinant Fusion Proteins, Retinal Neovascularization, RNA, Messenger},
	issn = {1524-4636},
	doi = {10.1161/ATVBAHA.113.302927},
	author = {Shao, Zhuo and Fu, Zhongjie and Stahl, Andreas and Joyal, Jean-S{\'e}bastien and Hatton, Colman and Juan, Aimee and Hurst, Christian and Evans, Lucy and Cui, Zhenghao and Pei, Dorothy and Gong, Yan and Xu, Dan and Tian, Katherine and Bogardus, Hannah and Edin, Matthew L and Lih, Fred and Sapieha, Przemyslaw and Chen, Jing and Panigrahy, Dipak and Hellstrom, Ann and Zeldin, Darryl C and Smith, Lois E H}
}
@article {1363202,
	title = {Choroid sprouting assay: an ex vivo model of microvascular angiogenesis},
	journal = {PLoS One},
	volume = {8},
	number = {7},
	year = {2013},
	month = {2013},
	pages = {e69552},
	abstract = {Angiogenesis of the microvasculature is central to the etiology of many diseases including proliferative retinopathy, age-related macular degeneration and cancer. A mouse model of microvascular angiogenesis would be very valuable and enable access to a wide range of genetically manipulated tissues that closely approximate small blood vessel growth in vivo. Vascular endothelial cells cultured in vitro are widely used, however, isolating pure vascular murine endothelial cells is technically challenging. A microvascular mouse explant model that is robust, quantitative and can be reproduced without difficulty would overcome these limitations. Here we characterized and optimized for reproducibility an organotypic microvascular angiogenesis mouse and rat model from the choroid, a microvascular bed in the posterior of eye. The choroidal tissues from C57BL/6J and 129S6/SvEvTac mice and Sprague Dawley rats were isolated and incubated in Matrigel. Vascular sprouting was comparable between choroid samples obtained from different animals of the same genetic background. The sprouting area, normalized to controls, was highly reproducible between independent experiments. We developed a semi-automated macro in ImageJ software to allow for more efficient quantification of sprouting area. Isolated choroid explants responded to manipulation of the external environment while maintaining the local interactions of endothelial cells with neighboring cells, including pericytes and macrophages as evidenced by immunohistochemistry and fluorescence-activated cell sorting (FACS) analysis. This reproducible ex vivo angiogenesis assay can be used to evaluate angiogenic potential of pharmacologic compounds on microvessels and can take advantage of genetically manipulated mouse tissue for microvascular disease research.},
	keywords = {Aging, Angiogenesis Inducing Agents, Animals, Biological Assay, Choroid, Culture Media, Human Umbilical Vein Endothelial Cells, Humans, Macrophages, Mice, Mice, Inbred C57BL, Microvessels, Models, Biological, Monocytes, Neovascularization, Physiologic, Pericytes, Rats, Rats, Sprague-Dawley, Reference Standards, Reproducibility of Results, Retinal Pigment Epithelium},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0069552},
	author = {Shao, Zhuo and Friedlander, Mollie and Hurst, Christian G and Cui, Zhenghao and Pei, Dorothy T and Evans, Lucy P and Juan, Aimee M and Tahiri, Houda and Tahir, Houda and Duhamel, Fran{\c c}ois and Chen, Jing and Sapieha, Przemyslaw and Chemtob, Sylvain and Joyal, Jean-S{\'e}bastien and Smith, Lois E H}
}
@article {1789021,
	title = {New Frontiers in Acanthamoeba Keratitis Diagnosis and Management},
	journal = {Biology (Basel)},
	volume = {12},
	number = {12},
	year = {2023},
	month = {2023 Dec 05},
	abstract = {Acanthamoeba Keratitis (AK) is a severe corneal infection caused by the Acanthamoeba species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, and treatment is made complicated by the organism{\textquoteright}s dual forms and increasing virulence, and delayed diagnosis. In this review, new approaches in AK diagnostics and treatment within the last 5 years are discussed. The English-language literature on PubMed was reviewed using the search terms "Acanthamoeba keratitis" and "diagnosis" or "treatment" and focused on studies published between 2018 and 2023. Two hundred sixty-five publications were initially identified, of which eighty-seven met inclusion and exclusion criteria. This review highlights the findings of these studies. Notably, advances in PCR-based diagnostics may be clinically implemented in the near future, while antibody-based and machine-learning approaches hold promise for the future. Single-drug topical therapy (0.08\% PHMB) may improve drug access and efficacy, while oral medication (i.e., miltefosine) may offer a treatment option for patients with recalcitrant disease.},
	issn = {2079-7737},
	doi = {10.3390/biology12121489},
	author = {Shareef, Omar and Shareef, Sana and Saeed, Hajirah N}
}
@article {1661597,
	title = {An alternative model for assessing mortality risk in Stevens Johnson syndrome/toxic epidermal necrolysis using a random forests classifier: A pilot study},
	journal = {Front Med (Lausanne)},
	volume = {9},
	year = {2022},
	month = {2022},
	pages = {935408},
	abstract = {INTRODUCTION: Mortality risk prediction is an important part of the clinical assessment in the Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) patient. The SCORTEN and ABCD-10 scoring systems have been used as predictive clinical tools for assessing this risk. However, some of the metrics required in calculating these scores, such as the total body surface area (TBSA) involvement, are difficult to calculate. In addition, TBSA involvement is calculated in a variety of ways and is observer dependent and subjective. The goal of this study was to develop an alternative method to predict mortality in patients with SJS/TEN. METHODS: Data was split into training and test datasets and preprocessed. Models were trained using five-fold cross validation. Out of several possible candidates, a random forests model was evaluated as being the most robust in predictive power for this dataset. Upon feature selection, a final random forests model was developed which was used for comparison against SCORTEN. RESULTS: The differences in both accuracy (p = 0.324) and area under the receiver operating characteristic curve (AUROC) (p = 0.318) between the final random forests model and the SCORTEN and ABCD-10 models were not statistically significant. As such, this alternative method performs similarly to SCORTEN while only requiring simple laboratory tests from the day of admission. DISCUSSION: This new alternative can make the mortality prediction process more efficient, along with providing a seamless implementation of the patient laboratory tests directly into the model from existing electronic health record (EHR) systems. Once the model was developed, a web application was built to deploy the model which integrates with the Epic EHR system on the Fast Healthcare Interoperability Resources (FHIR) Application Programming Interface (API); this only requires the patient medical record number and a date of the lab tests as parameters. This model ultimately allows clinicians to calculate patient mortality risk with only a few clicks. Further studies are needed for validation of this tool.},
	issn = {2296-858X},
	doi = {10.3389/fmed.2022.935408},
	author = {Shareef, Omar and Kwan, James T and Lau, Sarina and Tahboub, Mohammad Ali and Saeed, Hajirah N}
}
@article {1460364,
	title = {Transcriptional profiling of corneal stromal cells derived from patients with keratoconus},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 Aug 29},
	pages = {12567},
	abstract = {Keratoconus (KC) is a multi-factorial corneal ectasia with unknown etiology affecting approximately 1:2000 people worldwide. Dysregulated gene expression, using RNA-Seq technology, have been reported in KC corneal tissue. However, the differential expression of genes, in KC corneal stromal cells have been widely ignored. We utilized mRNA-Seq to analyze gene expression in primary human corneal stromal cells derived from five non-Keratoconus healthy (HCF) and four Keratoconus (HKC) donors. Selected genes were further validated using real time PCR (RT-PCR). We have identified 423 differentially expressed genes with 187 down- and 236 up-regulated in KC-affected corneal stromal cells. Gene ontology analysis using WebGestalt indicates the enrichment of genes involved in cell migration, extracellular matrix, adherens junction, and MAPK signaling. Our protein-protein interaction network analysis identified several network seeds, such as EGFR, NEDD4, SNTA1, LGALS3BP, HSPB1, SDC2, MME, and HIF1A. Our work provides an otherwise unknown information on the transcriptional changes in HKCs, and reveals critical mechanisms of the cellular compartment. It also highlights the importance of human-based in vitro studies on a disease that currently lacks strong biomarkers and animal models.},
	issn = {2045-2322},
	doi = {10.1038/s41598-019-48983-8},
	author = {Sharif, Rabab and Khaled, Mariam L and McKay, Tina B and Liu, Yutao and Karamichos, Dimitrios}
}
@article {1549005,
	title = {Subcircuits of Deep and Superficial CA1 Place Cells Support Efficient Spatial Coding across Heterogeneous Environments},
	journal = {Neuron},
	volume = {109},
	number = {2},
	year = {2021},
	month = {2021 Jan 20},
	pages = {363-376.e6},
	abstract = {The hippocampus is thought to guide navigation by forming a cognitive map of space. Different environments differ in geometry and the availability of cues that can be used for navigation. Although several spatial coding mechanisms are known to coexist in the hippocampus, how they are influenced by various environmental features is not well understood. To address this issue, we examined the spatial coding characteristics of hippocampal neurons in mice and rats navigating in different environments. We found that CA1 place cells located in the superficial sublayer were more active in cue-poor environments and preferentially used a firing rate code driven by intra-hippocampal inputs. In contrast, place cells located in the deep sublayer were more active in cue-rich environments and used a phase code driven by entorhinal inputs. Switching between these two spatial coding modes was supported by the interaction between excitatory gamma inputs and local inhibition.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2020.10.034},
	author = {Sharif, Farnaz and Tayebi, Behnam and Buzs{\'a}ki, Gy{\"o}rgy and Royer, S{\'e}bastien and Fernandez-Ruiz, Antonio}
}
@article {1629454,
	title = {Critical media attributes in E-beam sterilization of corneal tissue},
	journal = {Acta Biomater},
	volume = {138},
	year = {2022},
	month = {2022 01 15},
	pages = {218-227},
	abstract = {When ionizing irradiation interacts with a media, it can form reactive species that can react with the constituents of the system, leading to eradication of bioburden and sterilization of the tissue. Understanding the media{\textquoteright}s properties such as polarity is important to control and direct those reactive species to perform desired reactions. Using ethanol as a polarity modifier of water, we herein generated a series of media with varying relative polarities for electron beam (E-beam) irradiation of cornea at 25 kGy and studied how the irradiation media{\textquoteright}s polarity impacts properties of the cornea. After irradiation of corneal tissues, mechanical (tensile strength and modulus, elongation at break, and compression modulus), chemical, optical, structural, degradation, and biological properties of the corneal tissues were evaluated. Our study showed that irradiation in lower relative polarity media improved structural properties of the tissues yet reduced optical transmission; higher relative polarity reduced structural and optical properties of the cornea; and intermediate relative polarity (ethanol concentrations\&nbsp;=\&nbsp;20-30\% (v/v)) improved the structural properties, without compromising optical characteristics. Regardless of media polarity, irradiation did not negatively impact the biocompatibility of the corneal tissue. Our data shows that the absorbed ethanol can be flushed from the irradiated cornea to levels that are nontoxic to corneal and retinal cells. These findings suggest that the relative polarity of the irradiation media can be tuned to generate sterilized tissues, including corneal grafts, with engineered properties that are required for specific biomedical applications. STATEMENT OF SIGNIFICANCE: Extending the shelf-life of corneal tissue can improve general accessibility of cornea grafts for transplantation. Irradiation of donor corneas with E-beam is an emerging technology to sterilize the corneal tissues and enable their long-term storage at room temperature. Despite recent applications in clinical medicine, little is known about the effect of irradiation and preservation media{\textquoteright}s characteristics, such as polarity on the properties of irradiated corneas. Here, we have showed that the polarity of the media can be a valuable tool to change and control the properties of the irradiated tissue for transplantation.},
	keywords = {Cornea, Corneal Transplantation, Electrons, Gamma Rays, Sterilization},
	issn = {1878-7568},
	doi = {10.1016/j.actbio.2021.10.033},
	author = {Sharifi, Sina and Sharifi, Hannah and Akbari, Ali and Lei, Fengyang and Dohlman, Claes H and Gonzalez-Andrades, Miguel and Guild, Curtis and Paschalis, Eleftherios I and Chodosh, James}
}
@article {1658648,
	title = {Electrospun-Reinforced Suturable Biodegradable Artificial Cornea},
	journal = {ACS Appl Bio Mater},
	volume = {5},
	number = {12},
	year = {2022},
	month = {2022 Dec 19},
	pages = {5716-5727},
	abstract = {Despite rigorous investigations, the hydrogels currently available to replace damaged tissues, such as the cornea, cannot fulfill mechanical and structural requirements and, more importantly, cannot be sutured into host tissues due to the lack of hierarchical structures to dissipate exerted stress. In this report, solution electrospinning of polycaprolactone (PCL), protein-based hydrogel perfusion, and layer-by-layer stacking are used to generate a hydrogel-microfiber composite with varying PCL fiber diameters and hydrogel concentrations. Integrating PCL microfibers into the hydrogel synergistically improves the mechanical properties and suturability of the construct up to 10-fold and 50-fold, respectively, compared to the hydrogel and microfiber scaffolds alone, approaching those of the corneal tissue. Human corneal cells cultured on composites are viable and can spread, proliferate, and retain phenotypic characteristics. Moreover, corneal stromal cells migrate into the scaffold, degrade it, and regenerate the extracellular matrix. The current hydrogel reinforcing system paves the way for producing suturable and, therefore, transplantable tissue constructs with desired mechanical properties.},
	keywords = {Cornea, Extracellular Matrix, Humans, Hydrogels, Tissue Engineering, Tissue Scaffolds},
	issn = {2576-6422},
	doi = {10.1021/acsabm.2c00751},
	author = {Sharifi, Sina and Sharifi, Hannah}
}
@article {1586158,
	title = {Toward electron-beam sterilization of a pre-assembled Boston keratoprosthesis},
	journal = {Ocul Surf},
	volume = {20},
	year = {2021},
	month = {2021 Mar 03},
	pages = {176-184},
	abstract = {PURPOSE: To evaluate the effects of electron-beam (E-beam) irradiation on the human cornea and the potential for E-beam sterilization of Boston keratoprosthesis (BK) devices when pre-assembled with a donor cornea prior to sterilization. METHODS: Human donor corneas and corneas pre-assembled in BK devices were immersed in recombinant human serum albumin (rHSA) media and E-beam irradiated at 25\&nbsp;kGy. Mechanical (tensile strength and modulus, and compression modulus), chemical, optical, structural, and degradation properties of the corneal tissue after irradiation and after 6 months of preservation were evaluated. RESULTS: The mechanical evaluation showed that E-beam irradiation enhanced the tensile and compression moduli of human donor corneas, with no impact on their tensile strength. By chemical and mechanical analysis, E-beam irradiation caused a minor degree of crosslinking between collagen fibrils. No ultrastructural changes due to E-beam irradiation were observed. E-beam irradiation slightly increased the stability of the cornea against collagenase-induced degradation and had no impact on glucose diffusion. The optical evaluation showed transparency of the cornea was maintained. E-beam irradiated corneal tissues and BK-cornea pre-assembled devices were stable for 6 months after room-temperature preservation. CONCLUSIONS: E-beam irradiation generated no detrimental effects on the corneal tissues or BK-cornea pre-assembled devices and improved native properties of the corneal tissue, enabling prolonged preservation at room temperature. The pre-assembly of BK in a donor cornea, followed by E-beam irradiation, offers the potential for an off-the-shelf, ready to implant keratoprosthesis device.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.02.009},
	author = {Sharifi, Sina and Sharifi, Hannah and Guild, Curtis and Islam, Mohammad Mirazul and Tran, Khoa D and Patzer, Corrina and Dohlman, Claes H and Paschalis, Eleftherios I and Gonzalez-Andrades, Miguel and Chodosh, James}
}
@article {1623349,
	title = {Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications},
	journal = {Bioact Mater},
	volume = {6},
	number = {11},
	year = {2021},
	month = {2021 Nov},
	pages = {3947-3961},
	abstract = {Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking. This chemical modification allows the obtaining of an elastic protein-based hydrogel (GELGYM) with excellent biomimetic properties, approaching those of the native tissue. GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95\&nbsp;MPa with compressive strains as high as 80\% compared to Gelatin-methacryloyl (GeIMA), the most studied derivative of gelatin used as a bioadhesive. GELGYM is also highly biocompatible and supports cellular adhesion, proliferation, and migration in both 2 and 3-dimensional cell-cultures. These characteristics along with its super adhesion to biological tissues such as cornea, aorta, heart, muscle, kidney, liver, and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation, tissue adhesive, wound dressing, bioprinting, and drug and cell delivery.},
	issn = {2452-199X},
	doi = {10.1016/j.bioactmat.2021.03.042},
	author = {Sharifi, Sina and Islam, Mohammad Mirazul and Sharifi, Hannah and Islam, Rakibul and Koza, Darrell and Reyes-Ortega, Felisa and Alba-Molina, David and Nilsson, Per H and Dohlman, Claes H and Mollnes, Tom Eirik and Chodosh, James and Gonzalez-Andrades, Miguel}
}
@article {1626106,
	title = {Systematic optimization of visible light-induced crosslinking conditions of gelatin methacryloyl (GelMA)},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Dec 02},
	pages = {23276},
	abstract = {Gelatin methacryloyl (GelMA) is one of the most widely used photo-crosslinkable biopolymers in tissue engineering. In in presence of an appropriate photoinitiator, the light activation triggers the crosslinking process, which provides shape fidelity and stability at physiological temperature. Although ultraviolet (UV) has been extensively explored for photo-crosslinking, its application has been linked to numerous biosafety concerns, originated from UV phototoxicity. Eosin Y, in combination with TEOA and VC, is a biosafe photoinitiation system that can be activated via visible light instead of UV and bypasses those biosafety concerns; however, the crosslinking system needs fine-tuning and optimization. In order to systematically optimize the crosslinking conditions, we herein independently varied the concentrations of Eosin Y [(EY)], triethanolamine (TEOA), vinyl caprolactam (VC), GelMA precursor, and crosslinking times and assessed the effect of those parameters on the properties the hydrogel. Our data showed that except EY, which exhibited an optimal concentration (~ 0.05\&nbsp;mM), increasing [TEOA], [VA], [GelMA], or crosslinking time improved mechanical (tensile strength/modulus and compressive modulus), adhesion (lap shear strength), swelling, biodegradation properties of the hydrogel. However, increasing the concentrations of crosslinking reagents ([TEOA], [VA], [GelMA]) reduced cell viability in 3-dimensional (3D) cell culture. This study enabled us to optimize the crosslinking conditions to improve the properties of the GelMA hydrogel and to generate a library of hydrogels with defined properties essential for different biomedical applications.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-02830-x},
	author = {Sharifi, Sina and Sharifi, Hannah and Akbari, Ali and Chodosh, James}
}
@article {1424817,
	title = {Finding an Optimal Corneal Xenograft Using Comparative Analysis of Corneal Matrix Proteins Across Species},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 Feb 12},
	pages = {1876},
	abstract = {Numerous animal species have been proposed as sources of corneal tissue for obtaining decellularized xenografts. The selection of an appropriate animal model must take into consideration the differences in the composition and structure of corneal proteins between humans and other animal species in order to minimize immune response and improve outcome of the xenotransplant. Here, we compared the amino-acid sequences of 16 proteins present in the corneal stromal matrix of 14 different animal species using Basic Local Alignment Search Tool, and calculated a similarity score compared to the respective human sequence. Primary amino acid structures, isoelectric point and grand average of hydropathy (GRAVY) values of the 7 most abundant proteins (i.e. collagen α-1 (I), α-1 (VI), α-2 (I) and α-3 (VI), as well as decorin, lumican, and keratocan) were also extracted and compared to those of human. The pig had the highest similarity score (91.8\%). All species showed a lower proline content compared to human. Isoelectric point of pig (7.1) was the closest to the human. Most species have higher GRAVY values compared to human except horse. Our results suggest that porcine cornea has a higher relative suitability for corneal transplantation into humans compared to other studied species.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-38342-4},
	author = {Sharifi, R and Yang, Y. and Adibnia, Y and Dohlman, C H and Chodosh, J and Gonzalez-Andrades, M}
}
@article {1580487,
	title = {Electron Beam Sterilization of Poly(Methyl Methacrylate)-Physicochemical and Biological Aspects},
	journal = {Macromol Biosci},
	volume = {21},
	number = {4},
	year = {2021},
	month = {2021 Apr},
	pages = {e2000379},
	abstract = {Electron beam (E-beam) irradiation is an attractive and efficient method for sterilizing clinically implantable medical devices made of natural and/or synthetic materials such as poly(methyl methacrylate)\&nbsp;(PMMA). As ionizing irradiation can affect the physicochemical properties of PMMA, understanding the consequences of E-beam sterilization on the intrinsic properties of PMMA is vital for clinical implementation. A detailed assessment of the chemical, optical, mechanical, morphological, and biological properties of medical-grade PMMA after E-beam sterilization at 25 and 50 kiloGray (kGy) is reported. Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry studies indicate that E-beam irradiation has minimal effect on the chemical properties of the PMMA at these doses. While 25 kGy irradiation does not alter the mechanical and optical properties of the PMMA, 50 kGy reduces the flexural strength and transparency by 10\% and 2\%, respectively. Atomic force microscopy demonstrates that E-beam irradiation reduces the surface roughness of PMMA in a dose dependent manner. Live-Dead, AlamarBlue, immunocytochemistry, and complement activation studies show that E-beam irradiation up to 50 kGy has no adverse effect on the biocompatibility of the PMMA. These findings suggest that E-beam irradiation at 25 kGy may be a safe and efficient alternative for PMMA sterilization.},
	issn = {1616-5195},
	doi = {10.1002/mabi.202000379},
	author = {Sharifi, Sina and Islam, Mohammad Mirazul and Sharifi, Hannah and Islam, Rakibul and Huq, Tahmida N and Nilsson, Per H and Mollnes, Tom E and Tran, Khoa D and Patzer, Corrina and Dohlman, Claes H and Patra, Hirak K and Paschalis, Eleftherios I and Gonzalez-Andrades, Miguel and Chodosh, James}
}
@article {1282151,
	title = {Diplopia after Strabismus Surgery},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Dec 01},
	pages = {1-6},
	abstract = {Diplopia is a disappointing and, at times, unanticipated consequence of what might otherwise be considered anatomically successful strabismus surgery. In this study, we review the existing literature regarding diplopia after strabismus surgery in the context of the senior author{\textquoteright}s experience. We divide postoperative diplopia types into cases that occur in the setting of normal binocular vision (or "normal" suppression) vs. cases that are the consequence of rare or anomalous sensorial adaptations. We then discuss how to identify patients at greatest risk based on history and preoperative testing, and we offer strategies for managing these sometimes-challenging cases.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353827},
	author = {Sharma, Medha and Hunter, David G}
}
@article {1351188,
	title = {ROS-GC interlocked Ca(2+)-sensor S100B protein signaling in cone photoreceptors: review},
	journal = {Front Mol Neurosci},
	volume = {7},
	year = {2014},
	month = {2014},
	pages = {21},
	abstract = {Photoreceptor rod outer segment membrane guanylate cyclase (ROS-GC) is central to visual transduction; it generates cyclic GMP, the second messenger of the photon signal. Photoexcited rhodopsin initiates a biochemical cascade that leads to a drop in the intracellular level of cyclic GMP and closure of cyclic nucleotide gated ion channels. Recovery of the photoresponse requires resynthesis of cyclic GMP, typically by a pair of ROS-GCs, 1 and 2. In rods, ROS-GCs exist as complexes with guanylate cyclase activating proteins (GCAPs), which are Ca(2+)-sensing elements. There is a light-induced fall in intracellular Ca(2+). As Ca(2+) dissociates from GCAPs in the 20-200 nM range, ROS-GC activity rises to quicken the photoresponse recovery. GCAPs then progressively turn down ROS-GC activity as Ca(2+) and cyclic GMP levels return to baseline. To date, GCAPs mediate the only known mechanism of ROS-GC regulation in the photoreceptors. However, in mammalian cone outer segments, cone synapses and ON bipolar cells, another Ca(2+) sensor protein, S100B, complexes with ROS-GC1 and senses the Ca(2+) signal with a K1/2 of 400 nM. Unlike GCAPs, S100B stimulates ROS-GC activity when Ca(2+) is bound. Thus, the ROS-GC system in cones functions as a Ca(2+) bimodal switch; with rising intracellular Ca(2+), its activity is first turned down by GCAPs and then turned up by S100B. This presentation provides a historical perspective on the role of S100B in the photoreceptors, offers a pictorial model for the "bimodal" operation of the ROS-GC switch and projects future tasks that are needed to understand its operation. Some accounts of this review have been adopted from the original publications of these authors.},
	issn = {1662-5099},
	doi = {10.3389/fnmol.2014.00021},
	author = {Sharma, Rameshwar K and Makino, Clint L and Hicks, David and Duda, Teresa}
}
@article {1658681,
	title = {The future of non-viral gene delivery for the treatment of inherited retinal diseases},
	journal = {Mol Ther Nucleic Acids},
	volume = {30},
	year = {2022},
	month = {2022 Dec 13},
	pages = {354},
	issn = {2162-2531},
	doi = {10.1016/j.omtn.2022.10.011},
	author = {Sharma, Jyoti and Paschalis, Eleftherios I}
}
@article {1333936,
	title = {Consecutive superior oblique palsy after adjustable suture spacer surgery for Brown syndrome: incidence and predicting risk},
	journal = {J AAPOS},
	year = {2018},
	month = {2018 Sep 17},
	abstract = {PURPOSE: To determine the incidence of and to identify characteristics predicting significant superior oblique palsy (SOP) after adjustable superior oblique suture spacer surgery for treatment of Brown syndrome. METHODS: The medical records of patients treated for unilateral Brown syndrome with adjustable suture spacers (2005-2016) were reviewed to identify possible association of age at surgery, spacer length, surgeon performing procedure, severity of Brown syndrome, preoperative hypotropia in primary position and affected side gaze, and reduction in Brown restriction on postoperative superior oblique function. "Good" postoperative superior oblique function was defined as absence of hypertropia and diplopia in primary position and no more than intermittent diplopia in downgaze comfortably fused with <=4Δ base-down or head tilt of \&lt;10{\textdegree}. Presence of postoperative hypertropia in primary position with increase in downgaze met criteria for significant SOP. Postoperative Brown restriction of <= -2 indicated resolution of Brown syndrome. RESULTS: Median age at surgery was 59 months, interquartile range (IQR) was 32-82 months, and median spacer length was 6 mm (range, 2-7 mm) for 19 included patients. Preoperative median hypotropia was 9Δ (IQR, 0Δ-12Δ) in primary position and 18Δ (IQR, 5Δ-22Δ) in affected side gaze. Of 19 patients, 16 (84\%) achieved sufficient resolution of Brown syndrome, but 6 (32\%) developed significant SOP. Modest preoperative hypotropia in affected side gaze was the only predictor of significant SOP (likelihood ratio test = 7.11; P = 0.008). Logistic regression modeling enabled estimation of risk of significant SOP based on preoperative side gaze hypotropia. CONCLUSIONS: Suture spacer surgery can result in significant SOP. Risk may be predicted by magnitude of preoperative side gaze hypotropia.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2018.04.017},
	author = {Sharma, Medha and MacKinnon, Sarah and Zurakowski, David and Dagi, Linda R}
}
@article {503961,
	title = {LONG-TERM EFFICACY OF SYSTEMIC INFLIXIMAB IN RECALCITRANT RETINAL VASCULITIS.},
	journal = {Retina},
	volume = {35},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {2641-6},
	abstract = {PURPOSE: To evaluate the efficacy of systemic infliximab for the induction of remission in patients with retinal vasculitis, inadequately responsive to other immunomodulatory therapy, based on fluorescein angiography grading for retinal vasculitis evaluation. METHODS: We analyzed 60 patients with retinal vasculitis, from the Massachusetts Eye Research and Surgery Institution in Cambridge, MA. Response to therapy was based on analysis of serial fluorescein angiography and fundus photography, including a baseline angiogram before initiation of infliximab. RESULTS: Sixty patients received infliximab therapy between July 2007 and July 2012 at Massachusetts Eye Research and Surgery Institution for a diagnosis of retinal vasculitis. All had previously showed a poor clinical response to other immunomodulatory regimens, or ceased therapy due to intolerable side effects. The initial dose of infliximab was 5 mg/kg in all patients and remained at this dose for the extent of treatment in 57 (95\%) patients. At 6 months, 45 of 51 (88.23\%) patients were maintaining remission with therapy, 5 (9.8\%) were in partial remission, and 1 patient had failed. At 12 months, 39 of 39 (100\%) patients were maintaining remission with therapy. CONCLUSION: Infliximab is effective for the treatment of recalcitrant noninfectious retinal vasculitis, refractory to conventional immunomodulatory therapy.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000624},
	author = {Sharma, Pramod K and Markov, Gueorgui T and Bajwa, Asima and Foster, C Stephen}
}
@article {397871,
	title = {Ca(2+) and Ca(2+)-interlocked membrane guanylate cyclase signal modulation of neuronal and cardiovascular signal transduction.},
	journal = {Front Mol Neurosci},
	volume = {8},
	year = {2015},
	month = {2015},
	pages = {7},
	issn = {1662-5099},
	doi = {10.3389/fnmol.2015.00007},
	author = {Sharma, Rameshwar K and Baehr, Wolfgang and Makino, Clint L and Duda, Teresa}
}
@article {1593846,
	title = {Repository Corticotropin Injection as an Alternative Treatment for Refractory Ocular Mucous Membrane Pemphigoid},
	journal = {Cornea},
	volume = {41},
	number = {1},
	year = {2022},
	month = {2022 Jan 01},
	pages = {45-51},
	abstract = {PURPOSE: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). METHODS: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. RESULTS: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80\%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60\%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. CONCLUSIONS: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.},
	keywords = {Adrenocorticotropic Hormone, Adult, Aged, Aged, 80 and over, Conjunctiva, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Hormones, Humans, Injections, Subcutaneous, Male, Middle Aged, Mucous Membrane, Pemphigoid, Benign Mucous Membrane, Retrospective Studies, Slit Lamp Microscopy, Treatment Outcome},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002771},
	author = {Sharon, Yael and Anesi, Stephen D and Martinez, Christine E and Huang, Andrew J W and Foster, Charles Stephen and Chu, David S}
}
@article {959471,
	title = {Alteration in cellular turnover and progenitor cell population in lacrimal glands from thrombospondin 1(-/-) mice, a model of dry eye.},
	journal = {Exp Eye Res},
	volume = {153},
	year = {2016},
	month = {2016 Dec},
	pages = {27-41},
	abstract = {The purpose of this study was to investigate the changes that occur in the lacrimal glands (LGs) in female thrombospondin 1 knockout (TSP1(-/-)) mice, a mouse model of the autoimmune disease Sjogren{\textquoteright}s syndrome. The LGs of 4, 12, and 24 week-old female TSP1(-/-) and C57BL/6J (wild type, WT) mice were used. qPCR was performed to measure cytokine expression. To study the architecture, LG sections were stained with hematoxylin and eosin. Cell proliferation was measured using bromo-deoxyuridine and immunohistochemistry. Amount of CD47 and stem cell markers was analyzed by western blot analysis and location by immunofluorescence microscopy. Expression of stem cell transcription factors was performed using Mouse Stem Cell Transcription Factors RT(2) Profiler PCR Array. Cytokine levels significantly increased in LGs of 24 week-old TSP1(-/-) mice while morphological changes were detected at 12 weeks. Proliferation was decreased in 12 week-old TSP1(-/-) mice. Three transcription factors were overexpressed and eleven underexpressed in TSP1(-/-) compared to WT LGs. The amount of CD47, Musashi1, and Sox2 was decreased while the amount of ABCG2 was increased in 12 week-old TSP1(-/-) mice. We conclude that TSP1 is necessary for maintaining normal LG homeostasis. Absence of TSP1 alters cytokine levels and stem cell transcription factors, LG cellular architecture, decreases cell proliferation, and alters amount of stem cell markers.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2016.09.011},
	author = {Shatos, Marie A and Hodges, Robin R and Morinaga, Masahiro and McNay, David E and Islam, Rakibul and Bhattacharya, Sumit and Li, Dayu and Turpie, Bruce and Makarenkova, Helen P and Masli, Sharmila and Utheim, Tor P and Dartt, Darlene A.}
}
@article {1364542,
	title = {Isolation and characterization of progenitor cells in uninjured, adult rat lacrimal gland},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {6},
	year = {2012},
	month = {2012 May 14},
	pages = {2749-59},
	abstract = {PURPOSE: The purpose of this study was to investigate the presence of progenitor cells in the uninjured, adult rat lacrimal gland (LG). METHODS: The presence of progenitor cells was examined in LG sections from male rats using antibodies against selected stem cell markers and α-smooth muscle actin (SMA), which marks myoepithelial cells (MECs), by immunofluorescence microscopy (IF). Small, immature cells were isolated after digestion of LG with collagenase and culture in RPMI 1640 for 2 weeks. Immature cells were examined for expression of stem cell markers by IF. Immature cell were grown in neuronal, epithelial, and myoepithelial cell media, and examined by light morphology and IF using antibodies to markers of different cell lineages. RESULTS: In the intact LGs, MECs expressed the stem cell markers nestin, Musashi 1, ABCG2, Pax6, Chx 10, ΔN p63, and Sox 2. All markers colocalized with SMA. Isolated immature cells contained Ki-67, nestin, Musashi 1, Pax 6, and CHX 10. In neuronal media, immature cells differentiated and assumed a neuronal cell morphology expressing neurofilament 200. In media for human corneal endothelial cells, immature cells differentiated, assumed cobblestone morphology, and labeled with the epithelial marker AE1/AE3. In RPMI media immature cells differentiated into cells with MEC-like morphology, and expressed the MEC markers SMA, α-actinin, adenylate cyclase II, and vimentin. CONCLUSIONS: We conclude that uninjured, adult LG contains progenitor cells that may be MECs, which can be isolated and differentiated into multiple lineages.},
	keywords = {Adult Stem Cells, Animals, Biomarkers, Cell Proliferation, Cells, Cultured, Epithelial Cells, Lacrimal Apparatus, Male, Microscopy, Fluorescence, Rats, Rats, Sprague-Dawley},
	issn = {1552-5783},
	doi = {10.1167/iovs.11-9025},
	author = {Shatos, Marie A and Haugaard-Kedstrom, Linda and Hodges, Robin R and Dartt, Darlene A.}
}
@article {1364545,
	title = {Effect of central corneal thickness on the long-term outcome of selective laser trabeculoplasty as primary treatment for ocular hypertension and primary open-angle glaucoma},
	journal = {Cornea},
	volume = {31},
	number = {8},
	year = {2012},
	month = {2012 Aug},
	pages = {883-6},
	abstract = {PURPOSE: To determine if central corneal thickness (CCT) impacts the intraocular pressure (IOP)-lowering effect of selective laser trabeculoplasty (SLT) in patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG). METHODS: A retrospective chart review of consecutive patients, who underwent SLT as primary treatment for OHT and POAG, between 2002 and 2005, was performed. Partial correlation analysis was performed to correlate the CCT to the percentage of IOP reduction at 3 to 30 months after SLT. Independent samples t test was performed to compare mean percentage of IOP reduction in eyes with CCT less than 555 μm versus CCT 555 μm or greater. RESULTS: Eighty eyes of 47 patients were identified. The partial correlation coefficient value between the CCT and percentage of IOP reduction after SLT at 3 months was -0.253 (P = 0.025), at 12 months it was -0.22 (P = 0.049), and at 30 months it was 0.301 (P = 0.007). Independent samples t test showed that the mean percentage of IOP reduction in eyes with thinner corneas (CCT \&lt; 555 μm) was greater than that in thicker corneas (CCT >= 555 μm) at 3-, 6-, 9-, 12-, and 30-month post-SLT (P \&lt; 0.05). CONCLUSIONS: In patients with POAG and OHT, percentage of IOP reduction after SLT was significantly greater in eyes with thinner corneas (CCT \&lt; 555 μm). These findings indicate that patients treated with SLT as primary therapy who had thinner corneas demonstrated better IOP control for at least 30 months after SLT.},
	keywords = {Aged, Cornea, Female, Follow-Up Studies, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Laser Therapy, Male, Ocular Hypertension, Organ Size, Retrospective Studies, Tonometry, Ocular, Trabeculectomy, Treatment Outcome},
	issn = {1536-4798},
	doi = {10.1097/ICO.0b013e318243f684},
	author = {Shazly, Tarek A and Latina, Mark A and Dagianis, John J and Chitturi, Satyakant}
}
@article {1364543,
	title = {Use of processed pericardium graft to plug patulous old sclerostomy track during glaucoma shunt revision for exposure},
	journal = {Ophthalmic Surg Lasers Imaging},
	volume = {43},
	number = {1},
	year = {2012},
	month = {2012 Jan-Feb},
	pages = {72-5},
	abstract = {The authors demonstrate a reproducible technique using processed pericardium to seal sclerostomy track during glaucoma shunt revision. The suggested method involves placement of a wedge-shaped processed pericardial graft into the old sclerostomy tract following tube explantation. The graft is trimmed and sutured to the sclera. The tube is reinserted into a new sclerostomy and then sutured in place and covered in the usual fashion. This method allowed relatively easy treatment of three patients with patulous sclerostomy with necrotic edges. A successful tube revision and repositioning of the tube using this technique was performed on three patients with exposed tubes. The intraocular pressure was between 8 and 12 mm Hg from postoperative day 1. The authors suggest the use of pericardium plug to adequately seal the old sclerostomy track during glaucoma shunt revision. The plug allows tube repositioning at a new site without the need to suture the friable sclerostomy edges.},
	keywords = {Glaucoma, Glaucoma Drainage Implants, Humans, Intraocular Pressure, Pericardium, Reoperation, Sclera, Sclerostomy, Suture Techniques},
	issn = {1938-2375},
	doi = {10.3928/15428877-20111020-01},
	author = {Shazly, Tarek A and Latina, Mark A}
}
@article {1364544,
	title = {Pediatric ocular injuries from airsoft toy guns},
	journal = {J Pediatr Ophthalmol Strabismus},
	volume = {49},
	number = {1},
	year = {2012},
	month = {2012 Jan-Feb},
	pages = {54-7},
	abstract = {PURPOSE: To report ocular injuries caused by airsoft guns in children. METHODS: A retrospective chart review of pediatric patients who sustained ocular injuries related to airsoft guns between November 2005 and December 2007. Place of trauma, presenting symptoms and signs, surgical interventions performed, and final visual outcome were reviewed. RESULTS: Thirty-two patients with a mean age of 8.8 {\textpm} 4.0 years (range: 1.5 to 18 years) were examined; 28 were boys (87.5\%). Presenting visual acuity ranged from hand motions to 20/20 and could not be assessed in 2 patients. Hyphema was a common finding that was present in 24 cases, corneal abrasions were present in 10 cases, and raised intraocular pressure was present in 7 cases. Seven patients presented with traumatic cataract, and two had iridodialysis. Immediate surgical intervention was performed in 7 patients and 7 patients were scheduled for elective surgery. The patients presented after an average of 1.9 {\textpm} 1.9 days (range: 4 hours to 6 days) after the injury. Average follow-up was 18 days (range: 7 days to 5 months). Final visual acuity was 20/200 or worse in 5 patients, 20/40 or better in 23 patients, and could not be assessed in 2 cases. CONCLUSION: Airsoft guns can cause a variety of serious injuries, sometimes necessitating operative intervention. The long-term morbidity from some of these injuries is significant. Airsoft guns are capable of inflicting serious and permanent ocular damage.},
	keywords = {Adolescent, Cataract, Child, Child, Preschool, Eye Injuries, Female, Follow-Up Studies, Humans, Hyphema, Infant, Iris, Lens, Crystalline, Male, Play and Playthings, Retrospective Studies, Visual Acuity, Wounds, Gunshot},
	issn = {1938-2405},
	doi = {10.3928/01913913-20110118-05},
	author = {Shazly, Tarek A and Al-Hussaini, A K}
}
@article {882991,
	title = {Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics.},
	journal = {Cell},
	volume = {166},
	number = {5},
	year = {2016},
	month = {2016 Aug 25},
	pages = {1308-1323.e30},
	abstract = {Patterns of gene expression can be used to characterize and classify neuronal types. It is challenging, however, to generate taxonomies that fulfill the essential criteria of being comprehensive, harmonizing with conventional classification schemes, and lacking superfluous subdivisions of genuine types. To address these challenges, we used massively parallel single-cell RNA profiling and optimized computational methods on a heterogeneous class of neurons, mouse retinal bipolar cells (BCs). From a population of \~{}25,000 BCs, we derived a molecular classification that identified 15 types, including all types observed previously and two novel types, one of which has a\&nbsp;non-canonical morphology and position. We validated the classification scheme and identified dozens of novel markers using methods that match molecular expression to cell morphology. This work provides a systematic methodology for achieving comprehensive molecular classification of neurons, identifies novel neuronal types, and uncovers transcriptional differences that distinguish types within a class.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2016.07.054},
	author = {Karthik Shekhar and Lapan, Sylvain W and Whitney, Irene E and Tran, Nicholas M and Macosko, Evan Z and Kowalczyk, Monika and Adiconis, Xian and Levin, Joshua Z and James Nemesh and Melissa Goldman and McCarroll, Steven A and Cepko, Constance L and Regev, Aviv and Sanes, Joshua R}
}
@article {959476,
	title = {Pediatric Idiopathic Intracranial Hypertension: Age, Gender, and Anthropometric Features at Diagnosis in a Large, Retrospective, Multisite Cohort.},
	journal = {Ophthalmology},
	volume = {123},
	number = {11},
	year = {2016},
	month = {2016 Nov},
	pages = {2424-2431},
	abstract = {PURPOSE: To examine anthropometric and maturational characteristics at diagnosis in pediatric idiopathic intracranial hypertension (IIH). DESIGN: Retrospective, international, multisite study. PARTICIPANTS: Pediatric patients (2-18 years of age at diagnosis) with IIH. MAIN OUTCOME MEASURES: Body mass index (BMI), height, and weight Z-scores; sexual maturation. METHODS: Cases of IIH were identified retrospectively based on diagnostic code, pediatric neuro-ophthalmologist databases, or both and updated diagnostic criteria (2013) were applied to confirm definite IIH. Anthropometric measurements were converted into age- and gender-specific height, weight, and BMI Z-scores CDC 2000 growth charts. When available, sexual maturation was noted. RESULTS: Two hundred thirty-three cases of definite IIH were identified across 8 sites. In boys, a moderate association between age and BMI Z-scores was noted (Pearson{\textquoteright}s correlation coefficient, 0.50; 95\% confidence interval [CI], 0.30-0.66; P \&lt; 0.001; n\&nbsp;= 72), and in girls, a weak association was noted (Pearson{\textquoteright}s correlation coefficient, 0.34; 95\% CI, 0.20-0.47; P \&lt; 0.001; n\&nbsp;= 161). The average patient was more likely to be overweight at diagnosis at age 6.7 years in girls and 8.7 years in boys, and obese at diagnosis at age 12.5 years in girls and 12.4 years in boys. Compared with age- and gender-matched reference values, early adolescent patients were taller for age (P\&nbsp;= 0.002 in girls and P\&nbsp;= 0.02 in boys). Data on Tanner staging, menarchal status, or both were available in 25\% of cases (n\&nbsp;= 57/233). Prepubertal participants (n\&nbsp;= 12) had lower average BMI Z-scores (0.95{\textpm}1.98) compared with pubertal participants (n\&nbsp;= 45; 1.92{\textpm}0.60), but this result did not reach statistical significance (P\&nbsp;=\&nbsp;0.09). CONCLUSIONS: With updated diagnostic criteria and pediatric-specific assessments, the present study identifies 3 subgroups of pediatric IIH: a young group that is not overweight, an early adolescent group that is either overweight or obese, and a late adolescent group that is mostly obese. Data also suggest that the early adolescent group with IIH may be taller than age- and gender-matched reference values. Understanding these features of pediatric IIH may help to illuminate the complex pathogenesis of this condition.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.08.004},
	author = {Sheldon, Claire A and Paley, Grace L and Xiao, Rui and Kesler, Anat and Eyal, Ori and Ko, Melissa W and Boisvert, Chantal J and Avery, Robert A and Salpietro, Vincenzo and Phillips, Paul H and Heidary, Gena and McCormack, Shana E and Liu, Grant T}
}
@article {314196,
	title = {The effect of central vision loss on perception of mutual gaze},
	journal = {Optom Vis Sci},
	volume = {91},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {1000-11},
	abstract = {PURPOSE: To evaluate the effects of central vision loss (CVL) on mutual gaze perception (knowing whether somebody else is looking at you), an important nonverbal visual cue in social interactions. METHODS: Twenty-three persons with CVL (visual acuity 20/50 to 20/200), 16 with a bilateral central scotoma and 7 without, and 23 age-matched control subjects completed a gaze perception task and a brief questionnaire. They adjusted the eyes of a life-size virtual head on a monitor at a 1-m distance until they either appeared to be looking straight at them or were at the extreme left/right or up/down positions at which the eyes still appeared to be looking toward them (defining the range of mutual gaze in the horizontal and vertical planes). RESULTS: The nonscotoma group did not differ from the control subjects in any gaze task measure. However, the gaze direction judgments of the scotoma group had significantly greater variability than those of the nonscotoma and control groups (p \&lt; 0.001). In addition, their mutual gaze range tended to be wider (p = 0.15), suggesting a more liberal judgment criterion. Contrast sensitivity was the strongest predictor of variability in gaze direction judgments followed by self-reported difficulties. CONCLUSIONS: Our results suggest that mutual gaze perception is relatively robust to CVL. However, a follow-up study that simulates less-than-optimal viewing conditions of everyday social interactions is needed. The gaze perception task holds promise as a research tool for investigating the effects of vision impairment on mutual gaze judgments. Self-reported difficulty and contrast sensitivity were both independent predictors of gaze perception performance, suggesting that the task captured higher-order as well as low-level visual abilities.},
	keywords = {Aged, Female, Fixation, Ocular, Humans, Macular Degeneration, Male, Middle Aged, Saccades, Scotoma, Surveys and Questionnaires, Vision, Low, Visual Fields, Visual Perception},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000000314},
	author = {Sheldon, Sarah and Quint, Jessilin and Hecht, Heiko and Bowers, Alex R}
}
@article {468971,
	title = {Assessing the Effect of a Glaucoma Surgical Curriculum in Resident Physicians.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {9},
	year = {2015},
	month = {2015 Sep 1},
	pages = {1077-80},
	abstract = {IMPORTANCE: Subspecialty surgical training is an important part of resident education. We changed the glaucoma rotation in which postgraduate year 4 residents worked with multiple attending physicians with varying teaching styles to a structured surgical curriculum led by 2 dedicated preceptors, and we evaluated the effect on residents{\textquoteright} surgical performance prospectively. OBSERVATIONS: A curriculum consisting of preoperative training, intraoperative teaching, postoperative feedback, and repetition was implemented for postgraduate year 4 residents between July 2, 2012, and June 30, 2014. In a class of 8 residents per year, the mean (SD) glaucoma surgical volume increased from 8.9 (0.8) cases in the prior year to 13.6 (2.5) in 2013 (mean difference, 4.8 cases; 95\% CI, 2.4-7.1; P = .001) and 14.8 (4.2) in 2014 (mean difference, 5.9 cases; 95\% CI, 2.1-9.6; P = .007). A self-assessment survey showed improvement in suturing (scores for each section range from 1 [worst] to 5 [best]; mean rating, 3.9 in the prior year vs 4.4 in 2013 [P = .04] and 4.5 in 2014 [P = .02]). A validated survey assessing overall surgical competency revealed improvement in handling adverse events (mean rating, 4.1 in the prior year vs 5.0 for both 2013 and 2014; both P \&lt; .001). CONCLUSIONS AND RELEVANCE: Despite the small sample size and nonrandomized study design, these data suggest that a structured surgical curriculum has advantages in teaching subspecialty surgery and might be considered by other ophthalmology training programs.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.1846},
	author = {Shen, Lucy Q and Kloek, Carolyn E and Turalba, Angela V}
}
@article {1626096,
	title = {Novel engineered, membrane-tethered VEGF-A variants promote formation of filopodia, proliferation, survival, and cord or tube formation by endothelial cells via persistent VEGFR2/ERK signaling and activation of CDC42/ROCK pathways},
	journal = {FASEB J},
	volume = {35},
	number = {12},
	year = {2021},
	month = {2021 12},
	pages = {e22036},
	abstract = {Therapeutic angiogenesis would be clinically valuable in situations such as peripheral vascular disease in diabetic patients and tissue reperfusion following ischemia or injury, but approaches using traditional isoforms of vascular endothelial growth factor-A (VEGF) have had little success. The isoform VEGF165 is both soluble and matrix-associated, but can cause pathologic vascular changes. Freely diffusible VEGF121 is not associated with pathologic angiogenesis, but its failure to remain in the vicinity of the targeted area presents therapeutic challenges. In this study, we evaluate the cellular effects of engineered VEGF variants that tether extracellular VEGF121 to the cell membrane with the goal of activating VEGF receptor 2 (VEGFR2) in a sustained, autologous fashion in endothelial cells. When expressed by primary human retinal endothelial cells (hRECs), the engineered, membrane-tethered variants eVEGF-38 and eVEGF-53 provide a lasting VEGF signal that induces cell proliferation and survival, increases endothelial permeability, promotes the formation of a cord/tube network, and stimulates the formation of elongated filopodia on the endothelial cells. The engineered VEGF variants activate VEGFR2, MAPK/ERK, and the Rho GTPase mediators CDC42 and ROCK, activities that are required for the formation of the elongated filopodia. The sustained, pro-angiogenic activities induced by eVEGF-38 and eVEGF-53\&nbsp;support the potential of engineered VEGF variants-overexpressing endothelial cells as a novel combination of gene and cell-based therapeutic strategy for stimulating endothelial cell-autologous therapeutic angiogenesis.},
	keywords = {cdc42 GTP-Binding Protein, Cell Movement, Cell Proliferation, Endothelial Cells, Gene Expression Regulation, Humans, MAP Kinase Signaling System, Mutation, Neovascularization, Physiologic, Pseudopodia, Retina, rho-Associated Kinases, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2},
	issn = {1530-6860},
	doi = {10.1096/fj.202100448RR},
	author = {Shen, Junhui and Rossato, Franco Aparecido and Cano, Issahy and Ng, Yin Shan Eric}
}
@article {1347445,
	title = {Novel engineered, membrane-localized variants of vascular endothelial growth factor (VEGF) protect retinal ganglion cells: a proof-of-concept study},
	journal = {Cell Death Dis},
	volume = {9},
	number = {10},
	year = {2018},
	month = {2018 Oct 03},
	pages = {1018},
	abstract = {Endogenous vascular endothelial growth factor (VEGF-A) can protect retinal ganglion cells (RGC) from stress-induced cell death in ocular hypertensive glaucoma. To exploit the neuroprotective function of VEGF-A for therapeutic application in ocular disorders such as glaucoma while minimizing unwanted vascular side effects, we engineered two novel VEGF variants, eVEGF-38 and eVEGF-53. These variants of the diffusible VEGF-A isoform VEGF121 are expressed as dimeric concatamers and remain tethered to the cell membrane, thus restricting the effects of the engineered VEGF to the cells expressing the protein. For comparison, we tested a Myc-tagged version of VEGF189, an isoform that binds tightly to the extracellular matrix and heparan sulfate proteoglycans at the cell surface, supporting only autocrine and localized juxtacrine signaling. In human retinal endothelial cells (hREC), expression of eVEGF-38, eVEGF-53, or VEGF189 increased VEGFR2 phosphorylation without increasing expression of pro-inflammatory markers, relative to VEGF165 protein and vector controls. AAV2-mediated transduction of eVEGF-38, eVEGF-53, or VEGF189 into primary mouse RGC promoted synaptogenesis and increased the average total length of neurites and axons per RGC by ~ 12-fold, an increase that was mediated by VEGFR2 and PI3K/AKT signaling. Expression of eVEGF-38 in primary RGC enhanced expression of genes associated with neuritogenesis, axon outgrowth, axon guidance, and cell survival. Transduction of primary RGC with any of the membrane-associated VEGF constructs increased survival both under normal culture conditions and in the presence of the cytotoxic chemicals HO (via VEGFR2/PI3K/AKT signaling) and N-methyl-D-aspartate\&nbsp;(via reduced Ca influx). Moreover, RGC number was increased in mouse embryonic stem cell-derived retinal organoid cultures transduced with the eVEGF-53 construct. The novel, engineered VEGF variants eVEGF-38 and eVEGF-53 show promise as potential therapeutics for retinal RGC neuroprotection when delivered using a gene therapy approach.},
	issn = {2041-4889},
	doi = {10.1038/s41419-018-1049-0},
	author = {Shen, Junhui and Xiao, Ru and Bair, Jeffrey and Wang, Fang and Vandenberghe, Luk H and Dartt, Darlene and Baranov, Petr and Ng, Yin Shan Eric}
}
@article {416976,
	title = {Peripheral Prism Glasses: Effects of Moving and Stationary Backgrounds.},
	journal = {Optom Vis Sci},
	volume = {92},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {412-420},
	abstract = {PURPOSE: Unilateral peripheral prisms for homonymous hemianopia (HH) expand the visual field through peripheral binocular visual confusion, a stimulus for binocular rivalry that could lead to reduced predominance and partial suppression of the prism image, thereby limiting device functionality. Using natural-scene images and motion videos, we evaluated whether detection was reduced in binocular compared with monocular viewing. METHODS: Detection rates of nine participants with HH or quadranopia and normal binocularity wearing peripheral prisms were determined for static checkerboard perimetry targets briefly presented in the prism expansion area and the seeing hemifield. Perimetry was conducted under monocular and binocular viewing with targets presented over videos of real-world driving scenes and still frame images derived from those videos. RESULTS: With unilateral prisms, detection rates in the prism expansion area were significantly lower in binocular than in monocular (prism eye) viewing on the motion background (medians, 13 and 58\%, respectively, p = 0.008) but not the still frame background (medians, 63 and 68\%, p = 0.123). When the stimulus for binocular rivalry was reduced by fitting prisms bilaterally in one HH and one normally sighted subject with simulated HH, prism-area detection rates on the motion background were not significantly different (p \&gt; 0.6) in binocular and monocular viewing. CONCLUSIONS: Conflicting binocular motion appears to be a stimulus for reduced predominance of the prism image in binocular viewing when using unilateral peripheral prisms. However, the effect was only found for relatively small targets. Further testing is needed to determine the extent to which this phenomenon might affect the functionality of unilateral peripheral prisms in more real-world situations.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000000552},
	author = {Shen, Jieming and Peli, Eli and Bowers, Alex R}
}
@article {1287971,
	title = {Difluprednate 0.05\% versus Prednisolone Acetate 1\% for Endogenous Anterior Uveitis: Pooled Efficacy Analysis of Two Phase 3 Studies},
	journal = {Ocul Immunol Inflamm},
	year = {2017},
	month = {2017 Dec 20},
	pages = {1-13},
	abstract = {PURPOSE: To analyse pooled data from 2 similar phase 3 noninferiority studies comparing difluprednate 0.05\% versus prednisolone acetate 1\% in patients with endogenous anterior uveitis. METHODS: Patients received difluprednate alternating with vehicle or prednisolone acetate for 14\&nbsp;days (8 drops/day in both groups), followed by tapering from day 14 to 28. All patients were observed until day 42. RESULTS: More patients on difluprednate than on prednisolone acetate were cleared of anterior chamber cells on day twenty one (71.3\% vs 54.7\%; p\&nbsp;=\&nbsp;0.02); results were similar at the other time points. Treatment withdrawals were higher with prednisolone acetate than difluprednate (19.8\% vs 7.4\%; log-rank p\&nbsp;=\&nbsp;0.02). Study discontinuation due to lack of efficacy was also higher with prednisolone acetate than difluprednate (14.0\% vs 0\%; p\&nbsp;=\&nbsp;0.0002 [pre-specified exploratory analysis]). CONCLUSIONS: More difluprednate-treated eyes were quiet following 21\&nbsp;days of treatment, and difluprednate-treated patients were much less likely to be withdrawn from the study because of treatment failure.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2017.1407433},
	author = {Sheppard, John D and Foster, C Stephen and Toyos, Melissa M and Markwardt, Kerry and Da Vanzo, Robert and Flynn, Thomas E and Kempen, John H}
}
@article {1474198,
	title = {Iontophoretic Dexamethasone Phosphate Compared to Topical Prednisolone Acetate 1\% for Noninfectious Anterior Segment Uveitis},
	journal = {Am J Ophthalmol},
	year = {2019},
	month = {2019 Nov 11},
	abstract = {PURPOSE: To evaluate the safety and efficacy of dexamethasone phosphate ophthalmic solution (EGP-437) delivered by transscleral iontophoresis using the EyeGate{\textregistered} II Drug Delivery System, compared to topical prednisolone acetate 1\% (PA 1\%), in subjects with noninfectious anterior uveitis. DESIGN: Prospective, randomized, double-masked, parallel-group, non-inferiority clinical trial METHODS: A total of 193 subjects with active noninfectious anterior uveitis (anterior chamber [AC] cell count >=11 cells) were randomized to EGP-437 delivered via iontophoresis (Days 0 and 7) or self-administered PA 1\% daily (tapered schedule, Days 0-28). Masking was maintained with placebo iontophoresis/eyedrops. The primary efficacy endpoint was the proportion of subjects with an AC cell count of zero on Day 14; noninferiority of EGP-437 was defined if the lower limit of the confidence interval for the difference (EGP-437 minus PA 1\%) was less than -10\%. RESULTS: At Day 14, 32/96 (33.3\%) EGP-437 subjects and 32/97 (33.0\%) PA 1\% subjects had an AC cell count of zero (difference [95\% confidence interval], 0.34 [-12.94, 13.63]; P=0.064). Efficacy trended better with EGP-437 among patients with more severe baseline uveitis (AC cell count \&gt;25). Safety and tolerability were good with both treatments. EGP-437 subjects experienced fewer IOP elevations >=6 mm Hg versus PA 1\% subjects (13 vs 24 incidents through Day 28). CONCLUSIONS: Despite clinically similar response rates, statistical noninferiority of EGP-437 versus a tapered regimen of PA 1\% was not achieved. Numerical trends suggesting fewer IOP elevations with EGP-437, similar efficacy overall, and possibly better efficacy in more severe disease warrant further study.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.10.032},
	author = {Sheppard, John and Garg, Sunir and Lievens, Christopher and Brandano, Lisa and Wirostko, Barbara and Korenfeld, Michael and Raizman, Michael and Foster, C Stephen}
}
@article {1430539,
	title = {Hyaluronic Acid Gel Biodegradation After Intrapalpebral and Intraorbital Injection in Experimental Study},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {6},
	year = {2019},
	month = {2019 Nov/Dec},
	pages = {558-561},
	abstract = {PURPOSE: Amid the increasing clinical application of hyaluronic acid (HA) fillers in the ocular adnexa is a paucity of histological data concerning the fate of the injected material. The current study documents the in vivo biodegradation of HA deposited in the eyelid and orbit. METHODS: The study included 22 chinchilla rabbits. The right upper eyelid of 12 rabbits received a single 0.2 ml Restylane (Galderma, Uppsala, Sweden) subcutaneous injection. In 10 different rabbits, the right orbit was injected with 1.0 ml Restylane SubQ (Galderma, Uppsala, Sweden) in the extraconal space. The rabbits in the eyelid group were euthanized at 2 weeks, 1 month, 2, 4, 6, and 9 months, while the rabbits in the orbit group were euthanized at 1 month, 3, 6, 12, and 18 months. Histological analysis was performed on the harvested samples. RESULTS: In the eyelid, the HA assumed a sponge-like structure that diminished gradually over time. At 9 months, the injected HA partially persisted, mainly in the peripheral areas of injection. A similar histologic pattern was observed in the injected orbits, with slow changes persisting at the eighteenth month. In both cohorts, clear signs of collagen deposition and pseudocapsule formation were observed around HA droplets, with no signs inflammation. CONCLUSIONS: HA injected subcutaneously into the eyelid and orbit of rabbits undergoes slow and gradual biodegradation, with HA persisting to no less than 9 months in the eyelid and 18 months in orbit. Neocollagen synthesis and lack of hyaluronidase activity could explain the unexpectedly prolonged HA persistence.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001374},
	author = {Sheptulin, Vladimir and Fedorov, Anatoly and Prause, Jan and Fay, Aaron and Grusha, Yaroslav}
}
@article {1651229,
	title = {Voxel-Mirrored Homotopic Connectivity Is Altered in Meibomian Gland Dysfunction Patients That Are Morbidly Obese},
	journal = {Brain Sci},
	year = {2022},
	author = {Shi, YD and Shu, HY and Liu, LQ and Li, SQ and Liao, XL and Pan, YC and Su, T and Zhang, LJ and Kang, M and Ying, P and Shao, Y}
}
@article {1307464,
	title = {Lysyl oxidase inhibition via β-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro},
	journal = {Mol Med Rep},
	volume = {17},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {5029-5036},
	abstract = {Lysyl oxidase (LOX) is an enzyme that oxidizes lysine residues in collagens and elastin. It stabilizes or remodels the extracellular matrix and basement membrane of blood vessels. Current oncology studies have revealed that LOX is upregulated in invasive cancer cells and bolstered cell movement, and LOX was observed to promote the angiogenesis and migration of endothelial cells. In the present study, angiogenesis and migration were examined in human umbilical vein endothelial cells (HUVECs). Following cell treatment with 0.1-0.4\&nbsp;mM β-aminoproprionitrile (BAPN), a specific inhibitor of LOX, angiogenesis was analyzed with a fibrin gel in\&nbsp;vitro angiogenesis assay kit and migration was examined via a Boyden Chamber assay. Angiogenesis-associated gene expression was investigated with a microarray assay and confirmed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results showed that HUVEC angiogenesis substantially increased in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and phorbol 12-myristate\&nbsp;13-acetate (PMA). In addition, LOX inhibition blocked the angiogenesis stimulated by VEGF bFGF and PMA, and the inhibition of LOX reduced the migration of HUVECs. Furthermore, the microarray and RT-qPCR revealed that BAPN downregulated myeloid progenitor inhibitory factor\&nbsp;1, and western blot analysis demonstrated that BAPN decreased the phosphorylation of MAPK and Akt, suggesting that the specific inhibitor of LOX, BAPN, may serve as an alternative strategy for preventing angiogenesis.},
	issn = {1791-3004},
	doi = {10.3892/mmr.2018.8508},
	author = {Shi, Lin and Zhang, Ning and Liu, Hetao and Zhao, Lei and Liu, Jing and Wan, Juan and Wu, Wenyi and Lei, Hetian and Liu, Rongqing and Han, Mei}
}
@article {1528430,
	title = {Without low spatial frequencies, high resolution vision would be detrimental to motion perception},
	journal = {J Vis},
	volume = {20},
	number = {8},
	year = {2020},
	month = {2020 Aug 03},
	pages = {29},
	abstract = {A normally sighted person can see a grating of 30 cycles per degree or higher, but spatial frequencies needed for motion perception are much lower than that. It is unknown for natural images with a wide spectrum how all the visible spatial frequencies contribute to motion speed perception. In this work, we studied the effect of spatial frequency content on motion speed estimation for sequences of natural and stochastic pixel images by simulating different visual conditions, including normal vision, low vision (low-pass filtering), and complementary vision (high-pass filtering at the same cutoff frequencies of the corresponding low-vision conditions) conditions. Speed was computed using a biological motion energy-based computational model. In natural sequences, there was no difference in speed estimation error between normal vision and low vision conditions, but it was significantly higher for complementary vision conditions (containing only high-frequency components) at higher speeds. In stochastic sequences that had a flat frequency distribution, the error in normal vision condition was significantly larger compared with low vision conditions at high speeds. On the contrary, such a detrimental effect on speed estimation accuracy was not found for low spatial frequencies. The simulation results were consistent with the motion direction detection task performed by human observers viewing stochastic sequences. Together, these results (i) reiterate the importance of low frequencies in motion perception, and (ii) indicate that high frequencies may be detrimental for speed estimation when low frequency content is weak or not present.},
	issn = {1534-7362},
	doi = {10.1167/jov.20.8.29},
	author = {Shi, Cong and Pundlik, Shrinivas and Luo, Gang}
}
@article {1619417,
	title = {Comparison of cognitive performance between patients with Parkinson{\textquoteright}s disease and dystonia using an intraoperative recognition memory test},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Oct 20},
	pages = {20724},
	abstract = {Neuroscientific studies on the function of the basal ganglia often examine the behavioral performance of patients with movement disorders, such as Parkinson{\textquoteright}s disease (PD) and dystonia (DT), while simultaneously examining the underlying electrophysiological activity during deep brain stimulation surgery. Nevertheless, to date, there have been no studies comparing the cognitive performance of PD and DT patients during surgery. In this study, we assessed the memory function of PD and DT patients with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). We also tested their cognitive performance during the surgery using a continuous recognition memory test. The results of the MoCA and MMSE failed to reveal significant differences between the PD and DT patients. Additionally, no significant difference was detected by the intraoperative memory test between the PD and DT patients. The intraoperative memory test scores were highly correlated with the MMSE scores and MoCA scores. Our data suggest that DT patients perform similarly to PD patients in cognitive tests during surgery, and intraoperative memory tests can be used as a quick memory assessment tool during surgery.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-99317-6},
	author = {Shi, Lin and Yuan, Tianshuo and Fan, Shiying and Zheng, Jie and Diao, Yu and Qin, Guofan and Liu, Defeng and Zhu, Guanyu and Qin, Kai and Liu, Huanguang and Zhang, Hua and Yang, Anchao and Meng, Fangang and Zhang, Jianguo}
}
@article {1653576,
	title = {Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer{\textquoteright}s-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia},
	journal = {Acta Neuropathol Commun},
	volume = {10},
	number = {1},
	year = {2022},
	month = {2022 Sep 08},
	pages = {136},
	abstract = {Single cell RNA sequencing studies identified novel neurodegeneration-associated microglial (MGnD/DAM) subtypes activated around cerebral amyloid plaques. Micro-RNA (miR)-155 of the TREM2-APOE pathway was shown to be a key transcriptional regulator of MGnD microglial phenotype. Despite growing interest in studying manifestations of Alzheimer{\textquoteright}s disease (AD) in the retina, a CNS organ accessible to noninvasive high-resolution imaging, to date MGnD microglia have not been studied in the AD retina. Here, we discovered the presence and increased populations of Clec7a+ and Galectin-3+ MGnD microglia in retinas of transgenic APPSWE/PS1L166P AD-model mice. Conditionally targeting MGnD microglia by miR-155 ablation via the tamoxifen-inducible CreERT2 system in APPSWE/PS1L166P mice diminished retinal Clec7a+ and Galectin-3+ microglial populations while increasing homeostatic P2ry12+ microglia. Retinal MGnD microglia were often adhering to microvessels; their depletion protected the inner blood-retina barrier and reduced vascular amyloidosis. Microglial miR-155 depletion further limits retinal inflammation. Mass spectrometry analysis revealed enhanced retinal PI3K-Akt signaling and predicted IL-8 and Spp1 decreases in mice with microglia-specific miR-155 knockout. Overall, this study identified MGnD microglia in APPSWE/PS1L166P mouse retina. Transcriptional regulation of these dysfunctional microglia mitigated retinal inflammation and vasculopathy. The protective effects of microglial miR-155 ablation should shed light on potential treatments for retinal inflammation and vascular damage during AD and other ocular diseases.},
	keywords = {Alzheimer Disease, Animals, Disease Models, Animal, Galectin 3, Inflammation, Lectins, C-Type, Membrane Glycoproteins, Mice, Mice, Transgenic, Microglia, MicroRNAs, Phenotype, Phosphatidylinositol 3-Kinases, Receptors, Immunologic},
	issn = {2051-5960},
	doi = {10.1186/s40478-022-01439-z},
	author = {Shi, Haoshen and Yin, Zhuoran and Koronyo, Yosef and Fuchs, Dieu-Trang and Sheyn, Julia and Davis, Miyah R and Wilson, Jered W and Margeta, Milica A and Pitts, Kristen M and Herron, Shawn and Ikezu, Seiko and Ikezu, Tsuneya and Graham, Stuart L and Gupta, Vivek K and Black, Keith L and Mirzaei, Mehdi and Butovsky, Oleg and Koronyo-Hamaoui, Maya}
}
@article {913521,
	title = {Microcatheter-assisted trabeculotomy versus rigid probe trabeculotomy in childhood glaucoma.},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1257-62},
	abstract = {PURPOSE: To compare microcatheter-assisted trabeculotomy with standard rigid probe trabeculotomy for the treatment of childhood glaucoma. METHODS: The early postoperative (12 months) results of microcatheter-assisted trabeculotomy (group 1) performed by single surgeon were retrospectively compared with those of rigid probe trabeculotomy (group 2) performed by the same surgeon in patients treated for childhood glaucoma. Success was defined as an intraocular pressure (IOP) \&lt;21 mm Hg with at least a 30\% reduction from preoperative IOP with (qualified success) or without (complete success) the use of anti-glaucoma medication. RESULTS: A total of 43 eyes of 36 patients were included. Mean IOP in group 1 was significantly lower than that in group 2 at 6 months (17.0{\textpm}5.1 vs 22.5{\textpm}9.8; p=0.042), 9 months (16.3{\textpm}5.0 vs 21.6{\textpm}9.6; p=0.009) and 12 months (14.8{\textpm}2.5 vs 19.0{\textpm}7.1; p=0.049) postoperatively. The mean percentage reduction in IOP from preoperative to the last postoperative follow-up was greater in group 1 (47.3{\textpm}17.7\%) than in group 2 (34.2{\textpm}21.9\%) (p=0.036). group 1 demonstrated an 81.0\% complete and 86.4\% qualified success rate, exceeding the 51.6\% complete (p=0.060) and 61.9\% qualified (p=0.037) success rate of group 2. There were no long-term complications in either group, but choroidal detachment occurred in one eye in group 2. CONCLUSION: Microcatheter-assisted circumferential trabeculotomy is a more effective treatment and is as safe as traditional trabeculotomy with a rigid probe for primary congenital glaucoma in the early postoperative course. TRIAL REGISTRATION NUMBER: ChiCTR-OCC-15005789, Results.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-307880},
	author = {Shi, Yan and Wang, Huaizhou and Yin, Jia and Li, Meng and Zhang, Xifang and Xin, Chen and Chen, Xiaoya and Wang, Ningli}
}
@article {988011,
	title = {Outcomes of microcatheter-assisted trabeculotomy following failed angle surgeries in primary congenital glaucoma.},
	journal = {Eye (Lond)},
	volume = {31},
	number = {1},
	year = {2017},
	pages = {132-139},
	abstract = {PurposeTo report surgical outcomes of microcatheter-assisted trabeculotomy following failed angle surgeries, and compare those with no previous angle surgery, in primary congenital glaucoma (PCG).MethodsThe early postoperative (12 months) results of 42 eyes of 36 patients who underwent microcatheter-assisted trabeculotomy by single surgeon for PCG were retrospectively analyzed. Group 1, 20 eyes of 16 patients, had no previous angle surgery. Group 2, 22 eyes of 20 patients, had one or two previous failed angle surgeries. Success was defined as an intraocular pressure (IOP) \&lt;21 mm Hg with at least a 30\% reduction from preoperative IOP with (qualified success) or without (complete success) the use of antiglaucoma medication.ResultsMean IOP decreased from 31.5{\textpm}7.2 mm Hg on 3 (median, range: 1-5) medications in Group 1 and 34.6{\textpm}7.3 mm Hg on 3 (median, range: 1-4) medications in Group 2 preoperatively to 15.6{\textpm}3.1 mm Hg on 0 (median, range: 0-4) medications in Group 1 and 16.0{\textpm}4.6 mm Hg on 0 (median, range: 0-2) medications in Group 2 postoperatively at 12 months (both P\&lt;0.001), respectively. The mean percentage of IOP reduction from preoperative to last postoperative visit was 46.0{\textpm}20.1\% in Group 1 and 45.5{\textpm}25.0\% in Group 2, P=0.947. Qualified and complete successes were comparable between Group 1 and Group 2 (qualified success: 90.0\% vs 77.3\%, P=0.294; complete success: 78.9\% vs 77.3\%, P=0.853). Complications were minimal.ConclusionsMicrocatheter-assisted trabeculotomy achieved significant pressure-lowering effects with a reduction in medication use in PCG, and it represents a reasonable choice of initial and repeat surgical treatment for PCG.},
	issn = {1476-5454},
	doi = {10.1038/eye.2016.212},
	author = {Shi, Y and Wang, H. and Yin, J and Zhang, X. and Li, M and Xin, C and Chen, X. and Wang, N.}
}
@article {1309951,
	title = {A Compact VLSI System for Bio-Inspired Visual Motion Estimation},
	journal = {IEEE Trans Circuits Syst Video Technol},
	volume = {28},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {1021-1036},
	abstract = {This paper proposes a bio-inspired visual motion estimation algorithm based on motion energy, along with its compact very-large-scale integration (VLSI) architecture using low-cost embedded systems. The algorithm mimics motion perception functions of retina, V1, and MT neurons in a primate visual system. It involves operations of ternary edge extraction, spatiotemporal filtering, motion energy extraction, and velocity integration. Moreover, we propose the concept of confidence map to indicate the reliability of estimation results on each probing location. Our algorithm involves only additions and multiplications during runtime, which is suitable for low-cost hardware implementation. The proposed VLSI architecture employs multiple (frame, pixel, and operation) levels of pipeline and massively parallel processing arrays to boost the system performance. The array unit circuits are optimized to minimize hardware resource consumption. We have prototyped the proposed architecture on a low-cost field-programmable gate array platform (Zynq 7020) running at 53-MHz clock frequency. It achieved 30-frame/s real-time performance for velocity estimation on 160 {\texttimes} 120 probing locations. A comprehensive evaluation experiment showed that the estimated velocity by our prototype has relatively small errors (average endpoint error \&lt; 0.5 pixel and angular error \&lt; 10{\textdegree}) for most motion cases.},
	issn = {1051-8215},
	doi = {10.1109/TCSVT.2016.2630848},
	author = {Shi, Cong and Luo, Gang}
}
@article {1782346,
	title = {Artifact Correction in Retinal Nerve Fiber Layer Thickness Maps Using Deep Learning and Its Clinical Utility in Glaucoma},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {11},
	year = {2023},
	month = {2023 Nov 01},
	pages = {12},
	abstract = {PURPOSE: Correcting retinal nerve fiber layer thickness (RNFLT) artifacts in glaucoma with deep learning and evaluate its clinical usefulness. METHODS: We included 24,257 patients with optical coherence tomography and reliable visual field (VF) measurements within 30 days and 3,233 patients with reliable VF series of at least five measurements over >=4 years. The artifacts are defined as RNFLT less than the known floor value of 50 {\textmu}m. We selected 27,319 high-quality RNFLT maps with an artifact ratio (AR) of \&lt;2\% as the ground truth. We created pseudo-artifacts from 21,722 low-quality RNFLT maps with AR of \&gt;5\% and superimposed them on high-quality RNFLT maps to predict the artifact-free ground truth. We evaluated the impact of artifact correction on the structure-function relationship and progression forecasting. RESULTS: The mean absolute error and Pearson correlation of the artifact correction were 9.89 {\textmu}m and 0.90 (P \&lt; 0.001), respectively. Artifact correction improved R2 for VF prediction in RNFLT maps with AR of \&gt;10\% and AR of \&gt;20\% up to 0.03 and 0.04 (P \&lt; 0.001), respectively. Artifact correction improved (P \&lt; 0.05) the AUC for progression prediction in RNFLT maps with AR of <=10\%, \&gt;10\%, and \&gt;20\%: (1) total deviation pointwise progression: 0.68 to 0.69, 0.62 to 0.63, and 0.62 to 0.64; and (2) mean deviation fast progression: 0.67 to 0.68, 0.54 to 0.60, and 0.45 to 0.56. CONCLUSIONS: Artifact correction for RNFLTs improves VF and progression prediction in glaucoma. TRANSLATIONAL RELEVANCE: Our model improves clinical usability of RNFLT maps with artifacts.},
	keywords = {Artifacts, Deep Learning, Glaucoma, Humans, Nerve Fibers, Retina},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.11.12},
	author = {Shi, Min and Sun, Jessica A and Lokhande, Anagha and Tian, Yu and Luo, Yan and Tobias Elze and Shen, Lucy Q and Wang, Mengyu}
}
@article {1319479,
	title = {Optimization of Optomotor Response-based Visual Function Assessment in Mice},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Jun 26},
	pages = {9708},
	abstract = {Optomotor response/reflex (OMR) assays are emerging as a powerful and versatile tool for phenotypic study and new drug discovery for eye and brain disorders. Yet efficient OMR assessment for visual performance in mice remains a challenge. Existing OMR testing devices for mice require a lengthy procedure and may be subject to bias due to use of artificial criteria. We developed an optimized staircase protocol that utilizes mouse head pausing behavior as a novel indicator for the absence of OMR, to allow rapid and unambiguous vision assessment. It provided a highly sensitive and reliable method that can be easily implemented into automated or manual OMR systems to allow quick and unbiased assessment for visual acuity and contrast sensitivity in mice. The sensitivity and quantitative capacity of the protocol were validated using wild type mice and an inherited mouse model of retinal degeneration - mice carrying rhodopsin deficiency and exhibiting progressive loss of photoreceptors. Our OMR system with this protocol was capable of detecting progressive visual function decline that was closely correlated with the loss of photoreceptors in rhodopsin deficient mice. It provides significant advances over the existing methods in the currently available OMR devices in terms of sensitivity, accuracy and efficiency.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-27329-w},
	author = {Shi, Cong and Yuan, Xuedong and Chang, Karen and Cho, Kin-Sang and Xie, Xinmin Simon and Chen, Dong Feng and Luo, Gang}
}
@article {1333943,
	title = {A Streaming Motion Magnification Core for Smart Image Sensors},
	journal = {IEEE Trans Circuits Syst II Express Briefs},
	volume = {65},
	number = {9},
	year = {2018},
	month = {2018 Sep},
	pages = {1229-1233},
	abstract = {This paper proposes a modified Eulerian Video Magnification (EVM) algorithm and a hardware implementation of a motion magnification core for smart image sensors. Compared to the original EVM algorithm, we perform the pixel-wise temporal bandpass filtering only once rather than multiple times on all scale layers, to reduce the memory and multiplier requirement for hardware implementation. A pixel stream processing architecture with pipelined blocks is proposed for the magnification core, enabling it to readily fit common image sensing components with streaming pixel output, while achieving higher performance with lower system cost. We implemented an FPGA-based prototype that is able to process up to 90M pixels per second and magnify subtle motion. The motion magnification results are comparable to the original algorithm running on PC.},
	issn = {1549-7747},
	doi = {10.1109/TCSII.2017.2775583},
	author = {Shi, Cong and Luo, Gang}
}
@article {753696,
	title = {Diagnostic Performance of a Novel Three-Dimensional Neuroretinal Rim Parameter for Glaucoma Using High-Density Volume Scans.},
	journal = {Am J Ophthalmol},
	volume = {169},
	year = {2016},
	month = {2016 Sep},
	pages = {168-78},
	abstract = {PURPOSE: To evaluate the diagnostic performance of a 3-dimensional (3D) neuroretinal rim parameter, the minimum distance band (MDB), using optical coherence tomography (OCT) high-density volume scans for open-angle glaucoma. DESIGN: Reliability analysis. METHODS: setting: Institutional. STUDY POPULATION: Total of 163 patients (105 glaucoma and 58 healthy subjects). OBSERVATION PROCEDURES: One eye of each patient was included. MDB and retinal nerve fiber layer (RNFL) thickness values were determined for 4 quadrants and 4 sectors using a spectral-domain OCT device. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivities, specificities, and positive and negative predictive values. RESULTS: The best AUROC values of 3D MDB thickness for glaucoma and early glaucoma were for the overall globe (0.969, 0.952), followed by the inferior quadrant (0.966, 0.949) and inferior-temporal sector (0.966, 0.944), and then followed by the superior-temporal sector (0.964, 0.932) and superior quadrant (0.962, 0.924). All 3D MDB thickness AUROC values were higher than those of 2D RNFL thickness. Pairwise comparisons showed that the diagnostic performance of the 3D MDB parameter was significantly better than 2D RNFL thickness only for the nasal quadrant and inferior-nasal and superior-nasal sectors (P\&nbsp;= .023-.049). Combining 3D MDB with 2D RNFL parameters provided significantly better diagnostic performance (AUROC 0.984) than most single MDB parameters and all single RNFL parameters. CONCLUSIONS: Compared with the 2D RNFL thickness parameter, the 3D MDB neuroretinal rim thickness parameter had uniformly equal or better diagnostic performance for glaucoma in all regions and was significantly better in the nasal region.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.06.028},
	author = {Shieh, Eric and Lee, Ramon and Que, Christian and Srinivasan, Vivek and Guo, Rong and DeLuna, Regina and Pandit, Sumir and Simavli, Huseyin and Seevaratnam, Rajini and Tsikata, Edem and de Boer, Johannes and Chen, Teresa C}
}
@article {591276,
	title = {Spitz nevus arising in the eyelid of a teenager.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {2},
	year = {2016},
	month = {2016 Mar-Apr},
	pages = {228-35},
	abstract = {A 16-year-old boy developed over a 2-month interval a lightly pigmented left upper eyelid lesion measuring 1.5\&nbsp;mm in greatest diameter that, when excised, microscopically was hypercellular and composed almost exclusively of nonpigmented epithelioid cells that created florid, large intraepidermal junctional nests and sheets and nests of subepidermal cells. The diagnosis was a Spitz nevus. HMB-45, MART-1, and microphthalmia-associated transcription factor were all positive and established the melanocytic nature of the benign tumor. The Ki-67 proliferation index (5\%) and 2 mitoses/mm(2) were both low; p16 protein was immunohistochemically identified in the nevoid cells. We review the clinical, histopathologic, and other immunohistochemical features of this entity and provide a brief differential diagnosis (including separation from a Spitzoid melanoma). This is only the third eyelid Spitz nevus reported in the literature and is the most fully characterized immunohistochemically. At their present stage of development, contemporary immunohistochemical biomarkers, while providing supplemental information, nonetheless remain less than definitive in terms of reliably distinguishing benign from malignant Spitz lesions.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2015.10.002},
	author = {Shields, Patrick W and Jakobiec, Frederick A and Stagner, Anna M and Yoon, Michael K}
}
@article {1302173,
	title = {Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma},
	journal = {Hum Mol Genet},
	volume = {27},
	number = {8},
	year = {2018},
	month = {2018 Apr 15},
	pages = {1486-1496},
	abstract = {Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36~385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P ,
	issn = {1460-2083},
	doi = {10.1093/hmg/ddy053},
	author = {Shiga, Yukihiro and Akiyama, Masato and Nishiguchi, Koji M and Sato, Kota and Shimozawa, Nobuhiro and Takahashi, Atsushi and Momozawa, Yukihide and Hirata, Makoto and Matsuda, Koichi and Yamaji, Taiki and Iwasaki, Motoki and Tsugane, Shoichiro and Oze, Isao and Mikami, Haruo and Naito, Mariko and Wakai, Kenji and Yoshikawa, Munemitsu and Miyake, Masahiro and Yamashiro, Kenji and Kashiwagi, Kenji and Iwata, Takeshi and Mabuchi, Fumihiko and Takamoto, Mitsuko and Ozaki, Mineo and Kawase, Kazuhide and Aihara, Makoto and Araie, Makoto and Yamamoto, Tetsuya and Kiuchi, Yoshiaki and Nakamura, Makoto and Ikeda, Yasuhiro and Sonoda, Koh-Hei and Ishibashi, Tatsuro and Nitta, Koji and Iwase, Aiko and Shirato, Shiroaki and Oka, Yoshitaka and Satoh, Mamoru and Sasaki, Makoto and Fuse, Nobuo and Suzuki, Yoichi and Cheng, Ching-Yu and Khor, Chiea Chuen and Baskaran, Mani and Perera, Shamira and Aung, Tin and Vithana, Eranga N and Cooke Bailey, Jessica N and Kang, Jae H and Pasquale, Louis R and Haines, Jonathan L and Wiggs, Janey L and Burdon, Kathryn P and Gharahkhani, Puya and Hewitt, Alex W and Mackey, David A and Macgregor, Stuart and Craig, Jamie E and Allingham, R Rand and Hauser, Micheal and Ashaye, Adeyinka and Budenz, Donald L and Akafo, Stephan and Williams, Susan E I and Kamatani, Yoichiro and Nakazawa, Toru and Kubo, Michiaki}
}
@article {382616,
	title = {Onset of ocular graft-versus-host disease symptoms after allogeneic hematopoietic stem cell transplantation.},
	journal = {Cornea},
	volume = {34},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {243-7},
	abstract = {OBJECTIVE: To study the factors affecting the time to onset of ocular graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A retrospective chart review of 200 patients with ocular GVHD was performed to evaluate the association between various donor-recipient characteristics and the time to onset of ocular GVHD after allo-HSCT. RESULTS: The median time to onset of chronic ocular GVHD after allo-HSCT was 293 days (range, 26-2308 days). Patients receiving fully human leukocyte antigen (HLA)-matched transplants had a delayed onset of ocular GVHD (median, 294 days) compared with mismatched transplants (219 days; P = 0.029). HLA-matched transplants from related donors had delayed onset of ocular GVHD (307 days) compared with HLA-matched (286 days; P = 0.168) and HLA-mismatched (231 days; P = 0.015) transplants from unrelated donors. Ocular GVHD followed systemic GVHD in 76\% of patients but preceded systemic disease in 7\%, occurred concurrently in 15\%, and was not associated with systemic GVHD in 2\% of patients. The time elapsed between the occurrence of systemic and ocular GVHD was significantly longer in matched-related transplants (250 days) than in matched-unrelated transplants (120 days; P = 0.004). CONCLUSIONS: The onset of ocular GVHD after allo-HSCT is variable and is influenced by donor-recipient matching characteristics. In the majority of patients with GVHD, ocular involvement follows the occurrence of systemic manifestations; however, importantly, it can also precede or develop independently of systemic disease in a minority of patients. Regular ophthalmic follow-up is recommended after allo-HSCT regardless of concurrent systemic GVHD status.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000340},
	author = {Shikari, Hasanain and Amparo, Francisco and Saboo, Ujwala and Dana, Reza}
}
@article {1538353,
	title = {Micro-Fabrication of Components for a High-Density Sub-Retinal Visual Prosthesis},
	journal = {Micromachines (Basel)},
	volume = {11},
	number = {10},
	year = {2020},
	month = {2020 Oct 19},
	abstract = {We present a retrospective of unique micro-fabrication problems and solutions that were encountered through over 10 years of retinal prosthesis product development, first for the Boston Retinal Implant Project initiated at the Massachusetts Institute of Technology and at Harvard Medical School{\textquoteright}s teaching hospital, the Massachusetts Eye and Ear-and later at the startup company Bionic Eye Technologies, by some of the same personnel. These efforts culminated in the fabrication and assembly of 256+ channel visual prosthesis devices having flexible multi-electrode arrays that were successfully implanted sub-retinally in mini-pig animal models as part of our pre-clinical testing program. We report on the processing of the flexible multi-layered, planar and penetrating high-density electrode arrays, surgical tools for sub-retinal implantation, and other parts such as coil supports that facilitated the implantation of the peri-ocular device components. We begin with an overview of the implantable portion of our visual prosthesis system design, and describe in detail the micro-fabrication methods for creating the parts of our system that were assembled outside of our hermetically-sealed electronics package. We also note the unique surgical challenges that sub-retinal implantation of our micro-fabricated components presented, and how some of those issues were addressed through design, materials selection, and fabrication approaches.},
	issn = {2072-666X},
	doi = {10.3390/mi11100944},
	author = {Shire, Douglas B and Gingerich, Marcus D and Wong, Patricia I and Skvarla, Michael and Cogan, Stuart F and Chen, Jinghua and Wang, Wei and Rizzo, Joseph F}
}
@article {1430540,
	title = {Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels},
	journal = {Sci Adv},
	volume = {5},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {eaav1281},
	abstract = {Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.},
	issn = {2375-2548},
	doi = {10.1126/sciadv.aav1281},
	author = {Shirzaei Sani, Ehsan and Kheirkhah, Ahmad and Rana, Devyesh and Sun, Zhongmou and Foulsham, William and Sheikhi, Amir and Khademhosseini, Ali and Dana, Reza and Annabi, Nasim}
}
@article {560281,
	title = {Dietary Omega-3 Fatty Acids Suppress Experimental Autoimmune Uveitis in Association with Inhibition of Th1 and Th17 Cell Function.},
	journal = {PLoS One},
	volume = {10},
	number = {9},
	year = {2015},
	month = {2015},
	pages = {e0138241},
	abstract = {Omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs) inhibit the production of inflammatory mediators and thereby contribute to the regulation of inflammation. Experimental autoimmune uveitis (EAU) is a well-established animal model of autoimmune retinal inflammation. To investigate the potential effects of dietary intake of ω-3 LCPUFAs on uveitis, we examined the anti-inflammatory properties of these molecules in comparison with ω-6 LCPUFAs in a mouse EAU model. C57BL/6 mice were fed a diet containing ω-3 LCPUFAs or ω-6 LCPUFAs for 2 weeks before as well as after the induction of EAU by subcutaneous injection of a fragment of human interphotoreceptor retinoid-binding protein emulsified with complete Freund{\textquoteright}s adjuvant. Both clinical and histological scores for uveitis were smaller for mice fed ω-3 LCPUFAs than for those fed ω-6 LCPUFAs. The concentrations of the T helper 1 (Th1) cytokine interferon-γ and the Th17 cytokine interleukin-17 in intraocular fluid as well as the production of these cytokines by lymph node cells were reduced for mice fed ω-3 LCPUFAs. Furthermore, the amounts of mRNAs for the Th1- and Th17-related transcription factors T-bet and RORγt, respectively, were reduced both in the retina and in lymph node cells of mice fed ω-3 LCPUFAs. Our results thus show that a diet enriched in ω-3 LCPUFAs suppressed uveitis in mice in association with inhibition of Th1 and Th17 cell function.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0138241},
	author = {Shoda, Hiromi and Yanai, Ryoji and Yoshimura, Takeru and Nagai, Tomohiko and Kimura, Kazuhiro and Sobrin, Lucia and Connor, Kip M and Sakoda, Yukimi and Tamada, Koji and Ikeda, Tsunehiko and Sonoda, Koh-Hei}
}
@article {1598041,
	title = {Paired Optic Nerve Microvasculature and Nailfold Capillary Measurements in Primary Open-Angle Glaucoma},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {7},
	year = {2021},
	month = {2021 06 01},
	pages = {13},
	abstract = {Purpose: To assess microvascular beds in the optic nerve head (ONH), peripapillary tissue, and the nailfold in patients with primary open-angle glaucoma (POAG) versus controls. Methods: Patients with POAG (n = 22) and controls (n = 12) underwent swept-source optical coherence tomography angiography of ophthalmic microvasculature and nailfold video capillaroscopy of the hand. The main outcomes were vessel density (VD) and blood flow of the ONH, the peripapillary and the nailfold microvasculatures. Results: Patients with POAG were younger than controls (63.5 {\textpm} 9.4 vs. 69.9 {\textpm} 6.5 years, P = 0.03). Deep ONH VD and blood flow were lower in patients with POAG than controls (39.1\% {\textpm} 3.5\% vs. 43.8\% {\textpm} 5.7\%; 37.8\% {\textpm} 5.3\% vs. 46.0\% {\textpm} 7.8\%, respectively, P \&lt; 0.02 for both); similar results were observed with peripapillary VD (37.9 {\textpm} 2.6\%, 43.4 {\textpm} 7.6\%, respectively, P = 0.03). Nailfold capillary density and blood flow were lower in patients with POAG than controls (8.8 {\textpm} 1.0 vs. 9.8 {\textpm} 0.9 capillaries/mm; 19.9 {\textpm} 9.4 vs. 33.7 {\textpm} 9.8 pL/s, respectively; P \&lt; 0.009 for both). After adjusting for age and gender, deep ONH VD and blood flow, peripapillary VD, and nailfold capillary blood flow were lower in POAG than controls (β = -0.04, -0.07, -0.05, -13.19, respectively, P <= 0.046 for all). Among all participants, there were positive correlations between deep ONH and nailfold capillary blood flow (Pearson{\textquoteright}s correlation coefficient r = 0.42, P = 0.02), peripapillary and nailfold capillary density (r = 0.43, P = 0.03), and peripapillary and nailfold capillary blood flow (r = 0.49, P = 0.01). Conclusions: Patients with POAG demonstrated morphologic and hemodynamic alterations in both ophthalmic and nailfold microvascular beds compared to controls. Translational Relevance: The concomitant abnormalities in nailfold capillaries and relevant ocular vascular beds in POAG suggest that the microvasculature may be a target for POAG treatment.},
	keywords = {Capillaries, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Microvessels, Optic Disk, Visual Fields},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.7.13},
	author = {Shoji, Marissa K and Cousins, Clara C and Saini, Chhavi and Silva, Rafaella Nascimento E and Wang, Mengyu and Brauner, Stacey C and Greenstein, Scott H and Pasquale, Louis R and Shen, Lucy Q}
}
@article {1319480,
	title = {Epibulbar Mass With Upper Eyelid Cleft and Focal Scalp Alopecia in a Neonate: A New Case of Oculoectodermal Syndrome},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {4},
	year = {2018},
	month = {2018 Jul/Aug},
	pages = {e133-e136},
	abstract = {A female neonate presented with a pedunculated left lateral epibulbar mass protruding through the eyelids that originated from the temporal cornea and superolateral bulbar and palpebral conjunctiva. She had a cleft in the ipsilateral central upper eyelid with horizontal kink of the tarsus lateral to the cleft and focal patches of alopecia on the scalp. Histopathology of the epibulbar mass revealed conjunctival epithelium with underlying connective tissue, cartilage, bone, adipose, and lacrimal gland consistent with epibulbar dermoid. Genetic testing of the surgical specimen was positive for a KRAS mutation at position 146. MRI showed subarachnoid asymmetry around the left temporal lobe and a C1-C2 enhancing lesion. These clinical and molecular findings suggest that this patient has a new clinical variant of oculoectodermal syndrome, a rare disorder associated with somatic KRAS gene mutations and characterized clinically by epibulbar dermoids, alopecia, aplasia cutis, brain anomalies, umbilical hernias, and congenital heart defects.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001151},
	author = {Shoji, Marissa K and Saeed, Hajirah N and Habib, Larissa A and Freitag, Suzanne K}
}
@article {1511509,
	title = {The Use of Sirolimus for Treatment of Orbital Lymphatic Malformations: A Systematic Review},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {36},
	number = {3},
	year = {2020},
	month = {2020 May/Jun},
	pages = {215-221},
	abstract = {PURPOSE: Orbital lymphatic malformations are rare congenital choristomas associated with pain, proptosis, exposure keratopathy, and vision loss. Current treatments of surgery, drainage, and sclerotherapy may have adverse effects including risk of damage to surrounding structures, swelling, and malformation persistence or recrudescence. Sirolimus, which inhibits mammalian target of rapamycin, a regulator of cell growth and vascular endothelial growth factor expression, has successfully treated systemic vascular malformations. However, its efficacy and safety have not yet been well established for orbital lymphatic malformations. METHODS: Systematic review and analysis of relevant published literature were performed. PubMed, Embase, and World of Science searches were conducted for studies involving sirolimus treatment of orbital lymphatic malformations through July 2019. RESULTS: Nine case series and reports with 10 total patients who received sirolimus for treatment of orbital lymphatic malformations were included. The age at sirolimus initiation ranged from 1 week to 23 years. The malformation was lymphatic in 6 patients, lymphaticovenous in 3 patients, and lymphatic-arteriovenous in 1 patient. Six patients underwent ineffective prior therapy including sclerotherapy, surgery, or medical therapy. Initial sirolimus dosage ranged from 0.05 mg/kg twice a day to 1 mg twice a day, and duration ranged from 6 months to 53 months. Seven patients had partial response, and 3 patients, all of whom had a microcystic malformation component, experienced complete response. Adverse effects included mild reversible leukopenia, hypertriglyceridemia, hypercholesterolemia, and transaminitis with adverse effects denied or not specified for 6 patients. CONCLUSIONS: Sirolimus may be a safe and effective treatment for orbital lymphatic malformations, especially microcystic malformations.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001518},
	author = {Shoji, Marissa K and Shishido, Sachie and Freitag, Suzanne K}
}
@article {1593856,
	title = {Identifying Characteristics Predictive of Lost-to-follow-up (LTFU) Status in Amblyopia},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 May 13},
	abstract = {PURPOSE: To identify demographic and disease-related characteristics predictive of LTFU status in amblyopia treatment and create a risk model for predicting LTFU status. DESIGN: Retrospective cohort study METHODS: Setting: Single center, ophthalmology department at Boston Children{\textquoteright}s Hospital (BCH). PATIENTS: 2037 patients treated for amblyopia at BCH between 2010-2014. OBSERVATION PROCEDURE: LTFU was defined as patients who did not return after initial visit, excluding those who came for second opinion. Multiple variables were tested for association with LTFU status. OUTCOME MEASURE: Odds ratio of LTFU risk associated with each variable. Multivariate logistic regression was used to create a risk score for predicting LTFU status. RESULTS: A large proportion of patients (23\%) were LTFU after first visit. Older age, non-white race, lack of insurance, previous glasses or atropine treatment, and longer requested follow-up intervals were independent predictors of LTFU status. A multivariable risk score was created to predict probability of LTFU (AUC 0.68). CONCLUSIONS: Our comprehensive amblyopia database allows us to predict which patients are more likely to be LTFU after baseline visit, and develop strategies to mitigate these effects. These findings may help with practice efficiency and improve patient outcomes in the future by transitioning these analyses to an electronic medical record that could be programmed to provide continually updated decision support for individual patients based on large datasets.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.05.002},
	author = {Shoshany, Talia N and Chinn, Ryan N and Staffa, Steven J and Bishop, Kaila and Michalak, Suzanne and Hunter, David G}
}
@article {1474209,
	title = {Anomalous superior oblique muscles and tendons in congenital fibrosis of the extraocular muscles},
	journal = {J AAPOS},
	volume = {23},
	number = {6},
	year = {2019},
	month = {2019 Dec},
	pages = {325.e1-325.e6},
	abstract = {PURPOSE: To evaluate the finding of anomalous superior oblique muscles in congenital fibrosis of the extraocular muscles (CFEOM), a feature not previously emphasized in this condition. METHODS: The medical records of all patients clinically or genetically diagnosed with CFEOM at Boston Children{\textquoteright}s Hospital between 2010 and 2018 were reviewed retrospectively. Those who underwent strabismus surgery during the study period were included in the analysis. Baseline patient characteristics, type of CFEOM, results of genetic testing, and intraoperative features of the superior oblique muscle or tendon were recorded. RESULTS: Of 24 patients identified (age range, 1\&nbsp;month to 62\&nbsp;years), 10 (42\%) had genetically confirmed CFEOM, and 22 underwent strabismus surgery, 14 (64\%) involving the superior oblique muscle. Of these, 7 (50\%) had anomalously inserted tendons (most commonly attached nasal to the superior rectus muscle), whereas 7 (50\%) had increased superior oblique muscle tension. CONCLUSIONS: Half of CFEOM patients who underwent superior oblique surgery had abnormally inserted superior oblique tendons, and 50\% had tight muscles or abnormally thin tendons, findings that have not been well-characterized in this condition. The findings suggest that abnormal insertion of the superior oblique muscles and tendons are additional features of the disease process in CFEOM that have not been described previously. These features may contribute to the severe upgaze limitation in CFEOM and highlight the importance of superior oblique tenotomy in surgical management.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.09.014},
	author = {Shoshany, Talia N and Robson, Caroline D and Hunter, David G}
}
@article {1474204,
	title = {Effect of Primary Occlusion Therapy in Asymmetric, Bilateral Amblyopia},
	journal = {Am J Ophthalmol},
	volume = {211},
	year = {2020},
	month = {2020 Mar},
	pages = {87-93},
	abstract = {PURPOSE: Many bilateral amblyopia patients have asymmetric visual acuity (VA). There is no standard treatment for these patients, and outcomes have not been well described. Our goal is to compare VA outcomes in this group based on timing of occlusion therapy. DESIGN: Retrospective interventional comparative case series. METHODS: Setting: Institutional practice. PatientPopulation: Patients diagnosed with amblyopia at Boston Children{\textquoteright}s Hospital between 2010 and 2014. InclusionCriteria: VA >= 0.3 logMAR bilaterally by objective optotype-based measures, interocular difference (IOD) >= 0.18 logMAR, age 2-12 years. ExclusionCriteria: Loss to follow-up, managed surgically, deprivation amblyopia. Patients had either primary or secondary occlusion (primary\&nbsp;= initiated when VA >= 0.3 logMAR bilaterally; secondary\&nbsp;= initiated to correct residual IOD once VA improved to <=0.18 logMAR in the stronger eye). ObservationProcedure: Patient demographics, VA, IOD, and stereopsis were compared between groups. OutcomeMeasures: VA improvement at 12-18\&nbsp;months and at last visits. RESULTS: Of 2,200 patients reviewed, 167 (7.6\%) had asymmetric, bilateral amblyopia; 98 met inclusion and exclusion criteria. Patients were equally divided between primary (n\&nbsp;= 50) and secondary (n\&nbsp;= 48) occlusion groups. There were no differences in demographics, baseline VA, or IOD between groups (P >= .22), although the primary occlusion group had a higher proportion of strabismic amblyopia (P\&nbsp;= .007). VA in both eyes, IOD, and stereopsis improved similarly between groups, even after stratifying by amblyopia subtype (P >= .48). The secondary occlusion group was more likely to achieve 20/30 bilaterally and IOD <= 1 line at 12-18\&nbsp;months (P <= .4), although this equalized by the last visit. CONCLUSION: In patients with asymmetric, bilateral amblyopia, VA improved by 4 lines in the weaker eye and 2 lines in the stronger eye, while IOD improved by 2 lines, irrespective of occlusion status. Primary occlusion thus provided no further benefit over spectacle correction alone.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.10.030},
	author = {Shoshany, Talia N and Michalak, Suzanne and Staffa, Steven J and Chinn, Ryan N and Bishop, Kaila and Hunter, David G}
}
@article {1517189,
	title = {Evaluating Amblyopia Treatment Success Using the American Academy of Ophthalmology IRIS50 Measures},
	journal = {Ophthalmology},
	volume = {127},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {836-838},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.01.041},
	author = {Shoshany, Talia N and Michalak, Suzanne M and Chinn, Ryan N and Staffa, Steven J and Hunter, David G}
}
@article {1677761,
	title = {Detection of visuomotor dysfunction in mild traumatic brain injury using binocular retinal polarization scanning},
	journal = {Brain Inj},
	volume = {37},
	number = {6},
	year = {2023},
	month = {2023 May 12},
	pages = {534-540},
	abstract = {OBJECTIVE: The head and intraocular trauma tool (HITT) is a portable, binocular retinal polarization scanner (RPS) that detects ocular fixation with high precision to assess visuomotor function. We conducted a pilot evaluation of a prototype binocular RPS device to evaluate alterations in fixation stability, binocularity (convergence), and saccadic latency after mild traumatic brain injury (mTBI). METHODS: Two groups were studied prospectively: (1) single observation study of mTBI patients in a hospital ER (n = 7) and age-matched controls (n = 43); (2) high-school athletes preseason (n = 28), after sports-related mTBI (n = 3), and at season end (n = 5). Subjects were asked to fixate on an internal target and track randomly presented peripheral and central targets as fixation was assessed using binocular RPS. RESULTS: There were clinically and statistically significant alterations in the hospital ER group after mTBI, including a decrease in fixation stability (54.6\% in patents vs 90.2\% in controls, p = 0.014) and binocularity (28.7\% in patients vs 86.6\% in controls; p = 0.004). Similar trends, not statistically significant, were observed in saccadic latency in the hospital ER group as well as in the injured high school athletes. CONCLUSION: The HITT device shows promise as an objective, noninvasive method for assessment of the impact of mTBI on visuomotor function. Additional studies with larger patient populations are required to evaluate efficacy for clinical use.},
	keywords = {Athletes, Brain Concussion, Brain Injuries, Humans, Schools, Sports},
	issn = {1362-301X},
	doi = {10.1080/02699052.2023.2187089},
	author = {Shoshany, Talia N and Torres-Quinones, Carlos and Silverman, Erika and Shaka, Justin and Diaz-Arrastia, Ramon and Goldstein, Lee and Hunter, David G}
}
@article {1573132,
	title = {Screening first-degree relatives of glaucoma patients reveals barriers to participation},
	journal = {Br J Ophthalmol},
	year = {2021},
	month = {2021 Jan 08},
	abstract = {PURPOSE: To report the results of a glaucoma screening campaign targeting first-degree relatives of glaucoma patients in South India. METHODS: 1598 glaucoma patients were contacted via letter or letter and phone call and asked to bring their siblings and children to a glaucoma screening. Participants underwent standardised eye examinations and completed questionnaires that assessed barriers to participation and awareness of glaucoma risk. Two-proportion z-tests were used to compare categorical data. Costs associated with the screening were recorded. RESULTS: 206 probands (12.9\%) attended the screening along with 50 siblings and children. Probands were nearly twice as likely to attend if they had been contacted via both letter and phone call rather than letter only. Over half of probands reported that their relatives could not participate because they did not live in the region, and one-fifth reported that their relatives had other commitments. Fifty-eight per cent of the siblings and children who attended did not know that they were at increased risk for glaucoma due to their family history, and 32.0\% did not know that the relative who had invited them to the screening had glaucoma. Thirteen siblings and children (26.0\% of those who attended) were found to have findings concerning for glaucoma. The average cost per first-degree relative who was screened was INR2422 ({\textsterling}26). CONCLUSION: Participation in this glaucoma screening campaign was poor. The major barrier to participation was distance from the screening site and associated indirect costs. Better strategies for bringing first-degree relatives in for examinations are needed.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-317176},
	author = {Shroff, Sujani and Gu, Sophie Z and Vardhan S, Ashok and Mani, Iswarya and Aziz, Kanza and P, Namperumalsamy and Datta, Dipankar and Friedman, David S}
}
@article {1517181,
	title = {EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration},
	journal = {Int J Mol Sci},
	volume = {21},
	number = {12},
	year = {2020},
	month = {2020 Jun 16},
	abstract = {Epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.},
	issn = {1422-0067},
	doi = {10.3390/ijms21124271},
	author = {Shu, Daisy Y and Butcher, Erik and Saint-Geniez, Magali}
}
@article {1439863,
	title = {Epidermal Growth Factor Stimulates Transforming Growth Factor-Beta Receptor Type II Expression In Corneal Epithelial Cells},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 May 30},
	pages = {8079},
	abstract = {We previously demonstrated that inhibition of epidermal growth factor receptor (EGFR) slowed corneal epithelial migration. Here we examine the effect of EGF on transforming growth factor-beta receptor II (TGF-βRII) in a corneal wound-healing model and primary human corneal epithelial cells (pHCE). Corneal debridement wounds were made and allowed to heal {\textpm} Tyrphostin AG1478 (EGFR inhibitor), and assayed for EGFR activation and EGFR and TGF-βRII localization. Primary HCE were treated with EGF {\textpm} U0126 (MEK inhibitor) and assayed for TGF-βRII expression. EGFR activation was maximal 15 minutes after wounding and localized in the migrating epithelial cells. TGF-βRII localization was also observed in the migrating epithelium and was reduced when EGFR was blocked. When pHCE were treated with EGF for 6 hours, the cells produced enhanced levels of TGF-βRII, which was blocked by U0126. Downstream signaling pathways of MEK (p38 and ERK1/2) were then examined, and TGF-β1 and EGF were found to have differential effects on the phosphorylation of p38 and ERK1/2, with TGF-β1 upregulating p-p38 but not pERK1/2 and EGF upregulating pERK1/2 but not p-p38. Taken together, these data indicate that EGF stimulates TGF-βRII through ERK1/2 and EGFR signaling, suggesting interplay between EGF- and TGF-β-signaling pathways during corneal wound repair.},
	issn = {2045-2322},
	doi = {10.1038/s41598-019-42969-2},
	author = {Shu, Daisy Y and Hutcheon, Audrey E K and Zieske, James D and Guo, Xiaoqing}
}
@article {1452967,
	title = {Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury},
	journal = {Ocul Surf},
	year = {2019},
	month = {2019 Jul 03},
	abstract = {PURPOSE: Corneal injuries are associated with significant impairment in vision. Mesenchymal stem cells (MSCs) have been shown to limit inflammation and promote tissue repair at the ocular surface. Here, we evaluate the efficacies of different modes of MSC delivery (topical, subconjunctival, intraperitoneal [IP] and intravenous [IV]) to promote tissue repair and restore corneal transparency in a murine model of corneal injury. METHODS: MSCs were purified from the bone marrow of C57BL/6 J mice and expanded using plastic adherence in vitro. Corneal injury was created using an Algerbrush, and 0.5 {\texttimes} 10 MSCs/mouse were administered via topical, subconjunctival, IP or IV routes. Qdot-labeled MSCs were employed to determine the effect of route of administration on corneal and conjunctival MSC frequencies. Corneal opacity scores were calculated using ImageJ. Expression of inflammatory cytokines was quantified by qPCR, and infiltration of CD45 cells was evaluated by flow cytometry. RESULTS: Subconjunctival or IV administration results in increased frequencies of MSCs in ocular surface tissues following corneal injury, relative to topical or intraperitoneal delivery. Subconjunctival or IV administration reduces: (i) corneal opacity, (ii) tissue fibrosis as quantified by α-Sma expression, (iii) the expression of inflammatory cytokines (Il-1β and Tnf-α) and (iv) CD45 inflammatory cell infiltration relative to untreated injured control animals. Administration via subconjunctival or IV routes was observed to accelerate corneal repair by restoring tissue architecture and epithelial integrity. CONCLUSIONS: Our data suggest that subconjunctival or IV delivery of MSCs have superior therapeutic efficacy compared to topical or IP delivery following corneal injury.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2019.07.005},
	author = {Shukla, Sachin and Mittal, Sharad K and Foulsham, William and Elbasiony, Elsayed and Singhania, Disha and Sahu, Srikant K and Chauhan, Sunil K}
}
@article {1364546,
	title = {Confocal microscopy of corneal dystrophies},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {107-16},
	abstract = {In vivo confocal microscopy (IVCM) of the cornea is becoming an indispensable tool in the cellular study of corneal physiology and disease. This technique offers non-invasive imaging of the living cornea with images comparable to that of ex vivo histology. The ability to provide high-resolution images of all layers in the living cornea has resulted in new discoveries of corneal pathology at the cellular level. The IVCM analysis of corneal dystrophies is of importance to clinicians, as current methods of diagnosis involve slit-lamp characteristics, genetic analysis, and invasive biopsy. IVCM is helpful in evaluating the morphological characteristics of corneal dystrophies at the histological level and may be helpful in diagnosis, determination of progression, and understanding the pathophysiology of disease. The purpose of this review is to describe the principles, applications, and clinical correlation of IVCM in the study of corneal dystrophies.},
	keywords = {Corneal Dystrophies, Hereditary, Humans, Microscopy, Confocal},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.707276},
	author = {Shukla, Anita N and Cruzat, Andrea and Hamrah, Pedram}
}
@article {1651358,
	title = {Non-immune and immune functions of interleukin-36γ suppress epithelial repair at the ocular surface},
	journal = {FASEB J},
	year = {2022},
	author = {Shukla, S and Chow, K. and Elbasiony, E and Singh, RB and Mittal, S K and Chauhan, S K}
}
@article {1589739,
	title = {Predicting eyes at risk for rapid glaucoma progression based on an initial visual field test using machine learning},
	journal = {PLoS One},
	volume = {16},
	number = {4},
	year = {2021},
	month = {2021},
	pages = {e0249856},
	abstract = {OBJECTIVE: To assess whether machine learning algorithms (MLA) can predict eyes that will undergo rapid glaucoma progression based on an initial visual field (VF) test. DESIGN: Retrospective analysis of longitudinal data. SUBJECTS: 175,786 VFs (22,925 initial VFs) from 14,217 patients who completed >=5 reliable VFs at academic glaucoma centers were included. METHODS: Summary measures and reliability metrics from the initial VF and age were used to train MLA designed to predict the likelihood of rapid progression. Additionally, the neural network model was trained with point-wise threshold data in addition to summary measures, reliability metrics and age. 80\% of eyes were used for a training set and 20\% were used as a test set. MLA test set performance was assessed using the area under the receiver operating curve (AUC). Performance of models trained on initial VF data alone was compared to performance of models trained on data from the first two VFs. MAIN OUTCOME MEASURES: Accuracy in predicting future rapid progression defined as MD worsening more than 1 dB/year. RESULTS: 1,968 eyes (8.6\%) underwent rapid progression. The support vector machine model (AUC 0.72 [95\% CI 0.70-0.75]) most accurately predicted rapid progression when trained on initial VF data. Artificial neural network, random forest, logistic regression and na{\"\i}ve Bayes classifiers produced AUC of 0.72, 0.70, 0.69, 0.68 respectively. Models trained on data from the first two VFs performed no better than top models trained on the initial VF alone. Based on the odds ratio (OR) from logistic regression and variable importance plots from the random forest model, older age (OR: 1.41 per 10 year increment [95\% CI: 1.34 to 1.08]) and higher pattern standard deviation (OR: 1.31 per 5-dB increment [95\% CI: 1.18 to 1.46]) were the variables in the initial VF most strongly associated with rapid progression. CONCLUSIONS: MLA can be used to predict eyes at risk for rapid progression with modest accuracy based on an initial VF test. Incorporating additional clinical data to the current model may offer opportunities to predict patients most likely to rapidly progress with even greater accuracy.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0249856},
	author = {Shuldiner, Scott R and Boland, Michael V and Ramulu, Pradeep Y and De Moraes, C Gustavo and Tobias Elze and Myers, Jonathan and Pasquale, Louis and Wellik, Sarah and Yohannan, Jithin}
}
@article {1309946,
	title = {Combined Tenonplasty and Scleral Graft for Refractory Scleritis Following Pterygium Removal with Mitomycin C Application},
	journal = {J Ophthalmic Vis Res},
	volume = {13},
	number = {2},
	year = {2018},
	month = {2018 Apr-Jun},
	pages = {200-202},
	abstract = {Purpose: To report a surgical approach combining scleral patch graft and tenonplasty for successful management of refractory Pseudomonas scleritis following pterygium removal with mitomycin C application. Case Report: A 75-year-old diabetic woman with a history of prior pterygium excision and mitomycin C application developed infectious necrotizing scleritis caused by . Owing to progression of scleritis despite medical management, the patient underwent surgery. Intraoperatively, extensive scleral ischemia was noted. Therefore, debridement of the necrotic tissue, scleral graft, tenonplasty to bring blood vessels to the ischemic sclera, and amniotic membrane transplantation were performed. Postoperatively, no signs of ischemia or recurrence of infection were observed. During 6 months of follow-up, the patient achieved complete restoration of the globe integrity with a non-inflamed ocular surface. Conclusion: Through restoration of blood supply to the ischemic sclera, tenonplasty is an effective adjunctive procedure in addition to conventional scleral patch graft for the treatment of refractory Pseudomonas scleritis associated with ischemia.},
	issn = {2008-2010},
	doi = {10.4103/jovr.jovr_122_16},
	author = {Siatiri, Heidar and Mirzaee-Rad, Nima and Aggarwal, Shruti and Kheirkhah, Ahmad}
}
@article {1626111,
	title = {Epidemiology of United States Inpatient Open Globe Injuries from 2009-2015},
	journal = {Ophthalmic Epidemiol},
	volume = {28},
	number = {6},
	year = {2021},
	month = {2021 Dec},
	pages = {469-478},
	abstract = {PURPOSE: To study the epidemiology of inpatient open globe injuries (OGI) in the United States (US). METHODS: This was a retrospective cohort study of patients with a primary diagnosis of OGI in the National Inpatient Sample (NIS) from 2009 to 2015. Sociodemographic characteristics, including age, gender, race, ethnicity, insurance, and income were stratified for comparison. Annual prevalence rates were calculated using 2010 US Census data. Statistical analysis included Chi-square tests, ANCOVA, and Tukey tests. RESULTS: A total of 6,821 US inpatient hospital discharge records met inclusion/exclusion criteria. The estimated national prevalence of OGI during the 5-year period from 2009 to 2015 was 34,061 (95\% confidence interval [CI] 31,445-36,677). The overall annual prevalence rate was 1.58 per 100,000 per year (CI 1.56-1.59). Overall, average annual prevalence rates were highest among patients 85\&nbsp;years or older (7.72, CI 6.95-8.49), on Medicare (3.92, CI 3.84-4.00), males (2.28, CI 2.25-2.30), African Americans (2.38, CI 2.32-2.44), and Native Americans (1.80, CI 1.62-2.00). OGI rates were lowest among Whites (1.21, CI 1.19-1.22), females (0.89, CI 0.87-0.91), those with private insurance (0.84, CI 0.82-0.86), and Asians (0.69, CI 0.64-0.74). Being in the lowest income quartile was a risk factor for OGI (p \&lt;\&nbsp;.05). CONCLUSIONS: Inpatient OGIs disproportionately affected those over 85, young males, elderly females, patients of African-American descent, on Medicare, and in the lowest income quartile. Additionally, children and young children had lower rates of OGI compared to adolescents. Further studies should delineate causes for socioeconomic differences in OGI rates to guide future public health measures.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2021.1875008},
	author = {Siddiqui, Neha and Chen, Evan M and Parikh, Ravi and Douglas, Vivian Paraskevi and Douglas, Konstantinos Aa and Feng, Paula W and Armstrong, Grayson W}
}
@article {1445353,
	title = {Anterior Segment Applications of Optical Coherence Tomography Angiography},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 12},
	pages = {1-6},
	abstract = {: To review the current literature regarding optical coherence tomography angiography (OCT-A) applications in the anterior segment. : A literature search was performed for terms including OCT-Angiography, anterior segment, cornea, conjunctiva, iris, applications and use in ophthalmology. : Fifteen studies were identified, 14 in human subjects. Studies with OCT-A of the conjunctiva, episclera, cornea, and iris were identified, some with normal eyes imaged and others with various pathologies. Most of these studies imaged corneal neovascularization. Three studies described protocols used for image acquisition, one of which was referenced by two later papers. : OCT-A is a noninvasive technology with recent applications in the anterior segment. Several pilot studies have been performed on various anterior segment structures and disease states however standardization of image acquisition techniques is still needed. Future imaging could allow noninvasive and serial monitoring of pathology as well as recurrence after therapeutic intervention.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620805},
	author = {Siddiqui, Yusra and Yin, Jia}
}
@article {1318877,
	title = {Seasonal and Temporal Trends in Childhood Conjunctivitis in Burkina Faso},
	journal = {Am J Trop Med Hyg},
	year = {2018},
	month = {2018 May 14},
	abstract = {Acute conjunctivitis follows a seasonal pattern. Although its clinical course is typically self-limited, conjunctivitis epidemics incur a substantial economic burden because of missed school and work days. This study investigated seasonal and temporal trends of childhood conjunctivitis in the entire country of Burkina Faso from 2013 to 2016, using routine monthly surveillance from 2,444 government health facilities. A total of 783,314 cases were reported over the 4-year period. Conjunctivitis followed a seasonal pattern throughout the country, with a peak in April. A nationwide conjunctivitis outbreak with a peak in September 2016 was noted ( \&lt; 0.001), with an excess number of cases first detected in June 2016. Nationwide passive surveillance was able to detect an epidemic 3 months before its peak, which may aide in allocation of resources for containment and mitigation of transmission in future outbreaks.},
	issn = {1476-1645},
	doi = {10.4269/ajtmh.17-0642},
	author = {Si{\'e}, Ali and Diarra, Abdramane and Millogo, Ourohir{\'e} and Zongo, Augustin and Lebas, Elodie and B{\"a}rnighausen, Till and Chodosh, James and Porco, Travis C and Deiner, Michael S and Lietman, Thomas M and Keenan, Jeremy D and Oldenburg, Catherine E}
}
@article {1323941,
	title = {Reporting Harm in Glaucoma Surgical Trials: Systematic Review and a Consensus-Derived New Classification System},
	journal = {Am J Ophthalmol},
	volume = {194},
	year = {2018},
	month = {2018 Oct},
	pages = {153-162},
	abstract = {PURPOSE: To evaluate the standards of harm reporting for glaucoma surgical trials and to develop a classification system for reporting surgical complication severity. DESIGN: Systematic review and Delphi consensus method. METHODS: Systematic review of glaucoma surgical trials published from January 2010 until July 2017 with a quality assessment against the CONSORT checklist for harm. A Delphi method was employed to generate consensus grading (interquartile range <= 2) among international glaucoma experts (n\&nbsp;= 43) on severity of glaucoma surgical complications, and specifically for trabeculectomy and aqueous shunt complications, from\&nbsp;1\&nbsp;(no clinical significance) to 10 (most severe complication). RESULTS: Forty-seven studies were eligible. The items of the CONSORT checklist for harm that were most frequently missing were use of a validated instrument to report severity (0\%), withdrawals due to harm, and subgroup analyses, both reported in 3 publications (6.4\%). Most glaucoma experts participating in the Delphi process (80\%) completed the second round, and consensus was achieved for all but 1 complication. The least severe complications (graded 2) were "transient loss of vision," "early low intraocular pressure," "choroidal detachment anterior to equator," "small layered hyphema \&lt; 1\&nbsp;mm," and "increased lens opacity not clinically significant." The most severe complications (graded 10) were "endophthalmitis" and "permanent severe loss of vision (hand movements or worse)." CONCLUSIONS: Glaucoma surgical randomized controlled trials report frequency of complications, but their severity is rarely reported. The quality of harm reporting is poor. We propose the use of a newly developed system of classification for assessing the severity of surgical complications based on consensus.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.07.014},
	author = {Sii, Samantha and Barton, Keith and Pasquale, Louis R and Yamamoto, Tetsuya and King, Anthony J and Azuara-Blanco, Augusto}
}
@article {1629470,
	title = {Treatment for Epstein-Barr Virus-associated uveitis confirmed by polymerase chain reaction: Efficacy of Anti-Viral Agents and a literature review},
	journal = {J Clin Virol},
	volume = {147},
	year = {2022},
	month = {2022 Feb},
	pages = {105079},
	abstract = {BACKGROUND: There are still many research challenges and unanswered questions in relation to Epstein-Barr virus-associated uveitis. These include the presence of Epstein-Barr virus (EBV) DNA in asymptomatic patients, its pathogenicity in the uveitis eye, and the role of antiviral therapy for EBV-associated intraocular inflammation. METHODS: This was a retrospective review of prospectively collected data from the Ophthalmology Department, Rajavithi Hospital between 2015 and 2020. A qualitative assay using multiplex real-time PCR was performed to detect pathogen genes from specimens obtained from a total of 344 patients. The main outcome measure was treatment success defined by clinical improvement and absence of viral DNA confirmed by PCR. RESULTS: Of the 35 cases, 24 with complete data were enrolled in the study, including 22 with post-treatment PCR results. Sixty-seven percent were HIV-infected, and other plausible causes or coinfection with other pathogens were found in 75\% of patients. Cytomegalovirus (38\%) was the most common co-infecting pathogen. The most commonly employed regimen was a combination of systemic acyclovir and intravitreal ganciclovir injection (58\%). Of the 22 cases who had post-treatment PCR results, absence of detection of the virus by PCR in the intraocular fluid after treatment was demonstrated in 73\% of patients. CONCLUSION: Patients with EBV infection can be simultaneously co-infected with other pathogens. Systemic acyclovir and ganciclovir achieved clinical improvement in most cases, and EBV infection was cured in the majority of patients.},
	issn = {1873-5967},
	doi = {10.1016/j.jcv.2022.105079},
	author = {Silpa-Archa, Sukhum and Sriyuttagrai, Wararee and Foster, C Stephen}
}
@article {1655731,
	title = {ISOLATED RETINAL VASCULITIS: Prognostic Factors and Expanding the Role of Immunosuppressive Treatment in Retinal Vasculitis Associated With Positive QuantiFERON-TB Gold Test},
	journal = {Retina},
	volume = {42},
	number = {10},
	year = {2022},
	month = {2022 10 01},
	pages = {1897-1908},
	abstract = {PURPOSE: To identify prognostic factors for poor visual outcomes in patients with isolated retinal vasculitis and to elucidate the outcome of immunosuppressive treatment without the use of antituberculosis drugs for patients with retinal vasculitis associated with a positive QuantiFERON-TB Gold In-Tube (QFT) test. METHODS: A retrospective chart review was performed of patients presenting with retinal vasculitis. After the diagnosis of active retinal vasculitis had been confirmed by fluorescein angiography and other possible causes of retinal vasculitis had been excluded, patients were categorized into two groups by their QFT result. Potential associated factors between the poor and good visual outcome groups were statistically analyzed by the chi-square test and logistic regression model with generalized estimating equations. RESULTS: Seventy-three eyes (48 patients) were enrolled in this study. After univariate analysis, multivariate logistic regression analysis was performed and revealed that logMAR visual acuity at the initial visit ( P = 0.01) and outer retinal disruption ( P = 0.03) were the two factors significantly associated with poor visual outcomes. Systemic corticosteroids were administered without the use of antituberculosis drugs to all 16 cases of presumed tuberculous retinal vasculitis associated with positive QFT (26 eyes), 10 (63\%) of whom were given nonsteroidal immunosuppressive drugs and achieved inflammatory control and treatment success. CONCLUSION: Risk factors leading to poor visual outcome in patients with isolated retinal vasculitis have been identified. Immunosuppressive treatment without antituberculosis drugs seems to be a promising regimen for selected patients with presumed tuberculous retinal vasculitis under vigilant care.},
	keywords = {Adrenal Cortex Hormones, Antitubercular Agents, Humans, Immunosuppressive Agents, Prognosis, Retinal Vasculitis, Retrospective Studies, Tuberculosis},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003558},
	author = {Silpa-Archa, Sukhum and Sapthanakorn, Withawat and Foster, C Stephen}
}
@article {688651,
	title = {Vogt-Koyanagi-Harada syndrome: Perspectives for immunogenetics, multimodal imaging, and therapeutic options.},
	journal = {Autoimmun Rev},
	volume = {15},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {809-19},
	abstract = {Vogt-Koyanagi-Harada syndrome (VKH) is a bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological systems. The primary pathogenesis is T-cell-mediated autoimmune response directed towards melanocyte or melanocyte-associated antigens causing inflammation of the choroidal layer. This phenomenon usually leads to diffuse inflammatory conditions throughout most parts of eye before ocular complications ensue. The diagnosis is achieved mainly by clinical features according to the revised diagnostic criteria of VKH published in 2001, without confirmatory serologic tests as a requirement. However, ancillary tests, especially multimodal imaging, can reliably provide supportive evidence for the diagnosis of early cases, atypical presentations, and evaluation of management. Prompt treatment with systemic corticosteroids and early non-steroidal immunosuppressive drug therapy can lessen visually threatening ocular complications and bring about good visual recovery. Close monitoring warrants visual stabilization from disease recurrence and ocular complications. This article review aims not only to update comprehensive knowledge regarding VKH but also to emphasize three major perspectives of VKH: immunogenetics as the major pathogenesis of the disease, multimodal imaging, and therapeutic options. The role of anti-vascular endothelial growth factor therapy and drug-induced VKH is also provided.},
	issn = {1873-0183},
	doi = {10.1016/j.autrev.2016.04.001},
	author = {Silpa-Archa, Sukhum and Silpa-Archa, Narumol and Preble, Janine M and Foster, C Stephen}
}
@article {1549032,
	title = {Analysis of Three-Dimensional Choroidal Volume with Enhanced Depth Imaging Findings in Patients with Recurrent Vogt-Koyanagi-Harada Disease},
	journal = {Curr Eye Res},
	volume = {46},
	number = {7},
	year = {2021},
	month = {2021 Jul},
	pages = {1010-1017},
	abstract = {Purpose: To demonstrate changes in three-dimensional choroidal volume with enhanced depth imaging optical coherence tomography (EDI-OCT) in patients with recurrent stage of Vogt-Koyanagi-Harada disease (VKH).Materials and Methods: This prospective comparative case series included 9 patients with recurrent VKH, 10 patients with quiet VKH, and 15 healthy controls after sample size was calculated. All VKH cases with recurrences underwent raster scanning with EDI-OCT at active and inactive stages of the disease.Results: All choroidal parameters in the active stage significantly reduced when the inflammation subsided: total choroidal volume (P =\&nbsp;.02), central choroidal volume (P =\&nbsp;.01), central choroidal thickness (P =\&nbsp;.03). The changes in central choroidal volume over the resolution phase were more pronounced than the changes in central choroidal thickness in 56\% of cases. Two cases presenting with only subclinical posterior segment recurrence had their choroidal parameters recovered after prompt treatment.Conclusions: In the recurrent stage of VKH, alteration in choroidal volume was evident by EDI-OCT even in an absence of anterior segment inflammation. Central choroidal volume may serve as a biomarker for detecting choroidal morphological change.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2020.1849732},
	author = {Silpa-Archa, Sukhum and Ittharat, Worapon and Chotcomwongse, Peranut and Preble, Janine M and Foster, C Stephen}
}
@article {1213851,
	title = {Culture-Positive Endogenous Endophthalmitis: An Eleven-Year Retrospective Study in the Central Region of Thailand},
	journal = {Ocul Immunol Inflamm},
	year = {2017},
	month = {2017 Oct 11},
	pages = {1-10},
	abstract = {PURPOSE: To report the characteristics of infection and prognostic factors of endogenous endophthalmitis (EE) over an 11-year period. METHODS: The clinical records of 41 eyes of 36 patients diagnosed with culture-proven EE at the Rajavithi Hospital were retrospectively reviewed. RESULTS: Median age at presentation was 58\&nbsp;years. Liver abscess (19\%) and urinary tract infections (19\%) were the most common sources of infection. The most common causative agents were gram-negative organisms (48\%). The most commonly isolated microorganism was Klebsiella pneumoniae (26.8\%). Worse initial visual acuity and severe intraocular inflammation at first presentation were equally associated with poor visual outcome in the multivariate model (adjusted odds ratio, 20.32; 95\% confidence interval [1.12-357.45]; P\&nbsp;=\&nbsp;0.040). CONCLUSIONS: Endogenous endophthalmitis usually has a poor visual prognosis. Liver abscess and urinary tract infections are common primary sites of infection. Poor initial visual acuity and severe intraocular inflammation at the initial presentation are predictors of poor visual outcome.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2017.1355469},
	author = {Silpa-Archa, Sukhum and Ponwong, Alisa and Preble, Janine M and Foster, C Stephen}
}
@article {680436,
	title = {Outcome of tocilizumab treatment in refractory ocular inflammatory diseases.},
	journal = {Acta Ophthalmol},
	volume = {94},
	number = {6},
	year = {2016},
	month = {2016 Sep},
	pages = {e400-6},
	abstract = {PURPOSE: To report the outcomes of tocilizumab treatment for refractory ocular inflammatory diseases. METHODS: A retrospective case series of 17 patients (28 eyes) diagnosed with recalcitrant ocular inflammatory diseases including uveitis (10 cases), scleritis (six cases) and orbital pseudotumour (one case), who received tocilizumab between April 2010 and March 2015. All patients were initiated with treatment of 4\&nbsp;mg/kg or 8\&nbsp;mg/kg tocilizumab. The primary outcome was absence of inflammation and achievement of steroid sparing at 6 and 9\&nbsp;months. Secondary outcomes were change in visual acuity and major adverse effects of tocilizumab causing discontinuation of the treatment. RESULTS: Mean age at initiation of tocilizumab was 41\&nbsp;{\textpm}\&nbsp;16\&nbsp;years. Prior to tocilizumab treatment, all patients underwent unsuccessful conventional immunosuppressive therapy while 94\% of patients (16/17) failed treatment with various biological agents. After tocilizumab administration, control of inflammation and steroid sparing were achieved in 63\% and 71\% of uveitis patients at 6 and 9\&nbsp;months, while 50\% of scleritis patients achieved the primary outcome at 6 and 9\&nbsp;months. Mean duration of tocilizumab therapy was 12.6\&nbsp;{\textpm}\&nbsp;10.0 (range, 2-35) months. Three of four patients who had a follow-up of at least 18 (range, 18-35) months experienced quiescent inflammation for up to 32\&nbsp;months of tocilizumab use until last visit. Four patients (24\%) discontinued tocilizumab due to serious side effects including neutropenia, unacceptable dizziness and nausea, severe angioedema and severe abdominal pain. CONCLUSION: Our series demonstrated moderate efficacy of tocilizumab in recalcitrant uveitis and scleritis. Serious adverse effects were not uncommon.},
	issn = {1755-3768},
	doi = {10.1111/aos.13015},
	author = {Silpa-Archa, Sukhum and Oray, Merih and Preble, Janine M and Foster, Charles Stephen}
}
@article {1629465,
	title = {Appraisal of vitreous syphilis antibody as a novel biomarker for the diagnosis of syphilitic uveitis: a prospective case-control study},
	journal = {Eye (Lond)},
	volume = {37},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {146-154},
	abstract = {PURPOSE: To determine the sensitivity and specificity of syphilis antibody tests in vitreous samples and to propose an algorithm using vitreous syphilis antibody as a supplementary test to confirm syphilitic uveitis (SU). METHODS: A prospective case-control study was conducted at the Retina and Uveitis Clinic from May 2017 to January 2020. Initially, patients were classified based on syphilis serology into group 1 (positive testing) and group 2 (negative testing). Group 1 was further divided into 2 subgroups (group 1A and 1B) depending on their relevant clinical manifestations and clinical improvement. Group 2 served as a control group. RESULTS: Thirty-eight patients were enrolled in the study: 14 in group 1A, 5 in group 1B, and 19 in group 2B. No patient was assigned to group 2A. All patients in group 1A, representing definite SU, completed syphilis test (rapid plasma reagin [RPR], enzyme immunoassay [EIA], and fluorescent treponemal antibody-absorption [FTA-ABS]) for vitreous, and all vitreous samples yielded positive results. Of the 5 subjects in group 1B, 3 cases were considered to be not SU with different conditions, and 2 were indeterminate for SU. They presented with different features not typical of SU, and they had variable and fewer positive syphilis antibody responses. The most sensitive test for detecting syphilis antibodies in vitreous was EIA (90.9\%), followed by RPR (80.0\%) and FTA-ABS IgG (78.9\%). EIA and FTA-ABS had the highest specificity, detecting 100\% of the syphilis antibody. CONCLUSIONS: Vitreous analysis of syphilis antibody can serve as a supplementary test to confirm SU in selected cases as the proposed algorithm.},
	keywords = {Antibodies, Bacterial, Biomarkers, Case-Control Studies, Humans, Sensitivity and Specificity, Syphilis, Uveitis},
	issn = {1476-5454},
	doi = {10.1038/s41433-021-01902-6},
	author = {Silpa-Archa, Sukhum and Hoopholerb, Tararat and Foster, Charles Stephen}
}
@article {688656,
	title = {Birdshot Retinochoroidopathy: Differences in Clinical Characteristics between Patients with Early and Late Age of Onset.},
	journal = {Ocul Immunol Inflamm},
	year = {2016},
	month = {2016 Apr 12},
	pages = {1-7},
	abstract = {PURPOSE: To describe differences in the clinical characteristics of birdshot retinochoroidopathy (BSRC) patients diagnosed early and later in life. METHODS: This is a retrospective cohort study. Age was primarily analyzed and 50 years of age at diagnosis was selected as a cut-off point. RESULTS: A total of 144 patients (288 eyes) were included; 68 with early-onset and 76 with late-onset BSRC. The younger group had a statistically significant higher rate of more severe iritis (p = 0.04); an average number of non-steroidal immunosuppressants and biologic agents (NSIB) (p = 0.04); and a prolonged time to initiation of NSIB (p = 0.01). There were only four patients (3\%) who had \&gt;0.5+ cells in the anterior chamber. CONCLUSIONS: Patients with early-onset BSRC carried a higher risk for anterior segment inflammation, had a more prolonged delay to initiation of treatment with NSIB, and required a greater number of NSIBs to achieve remission.},
	issn = {1744-5078},
	doi = {10.3109/09273948.2016.1158278},
	author = {Silpa-Archa, Sukhum and Cao, Jennifer H and Boonsopon, Sutasinee and Lee, Joan and Preble, Janine M and Foster, C Stephen}
}
@article {694756,
	title = {POOR PROGNOSTIC FACTORS IN PATIENTS WITH BIRDSHOT RETINOCHOROIDOPATHY.},
	journal = {Retina},
	volume = {36},
	number = {11},
	year = {2016},
	month = {2016 Nov},
	pages = {2220-2226},
	abstract = {PURPOSE: To identify prognostic factors for poor visual outcome in patients with birdshot retinochoroidopathy. METHODS: A case-control study of 98 patients with birdshot retinochoroidopathy (196 eyes) was evaluated with a follow-up period of at least 12 months. After exclusion of glaucoma, optic atrophy, and macular scar, the remaining eligible patients were categorized into two groups: poor visual outcomes and good visual outcomes. Poor visual outcome was defined as less than -6 mean deviation score on Swedish interactive threshold algorithm (SITA) short-wavelength automated perimetry (SWAP) test and abnormality (amplitude or implicit time) of 30 Hz flicker electroretinogram at 4-year follow-up and at the most recent visit for separate analysis. Potential factors between both groups were statistically analyzed by Chi-square test and logistic regression model. RESULTS: After the aforementioned exclusion, the remaining 77 patients with an average follow-up period of 52 {\textpm} 29 months (335 person-years, 36\% with follow-up of more than 5 years) were divided into two groups. Sixteen patients were categorized as having poor visual outcome. Univariate analysis identified significant association of abnormal 30 Hz flicker electroretinogram amplitude (P = 0.004), implicit time (P = 0.002), and SITA SWAP mean deviation at the initial visit (P \&lt; 0.001) in the poor visual outcome group. Multivariate logistic regression analysis identified only SITA SWAP mean deviation to be associated with poor visual outcome (adjusted odds ratio, 32.50; 95\% confidence interval [3.84-275.32]; P = 0.001) at the initial visit. To verify the model validity, an analysis of 42 patients at 4-year follow-up was performed and the outcome was confirmed (adjusted odds ratio, 8.80; 95\% confidence interval [1.58-49.16]; P = 0.013). CONCLUSION: Worse SITA SWAP mean deviation at the initial visit is a predictor of poor visual outcome in patients with birdshot retinochoroidopathy, and may serve as a proxy marker for delayed effective steroid sparing therapy in patients with birdshot retinochoroidopathy.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001051},
	author = {Silpa-Archa, Sukhum and Lee, Joan J and Boonsopon, Sutasinee and Liz{\'a}rraga, Marisol T and Preble, Janine M and Sujirarat, Dusit and Patel, Pranav and Foster, C Stephen}
}
@article {1559566,
	title = {Poor prognostic factors in post-traumatic endophthalmitis following open globe injury},
	journal = {Int J Ophthalmol},
	volume = {13},
	number = {12},
	year = {2020},
	month = {2020},
	pages = {1968-1975},
	abstract = {AIM: To demonstrate prognostic factors for poor visual outcome in patients with post-traumatic endophthalmitis (PTE) following open globe injury. METHODS: A retrospective study was conducted on 66 patients (66 eyes) with PTE following open globe injury from 2005 to 2015. Potential factors accounting for good and poor visual outcome were statistically analyzed by Chi-square test and Logistic regression model. RESULTS: In 66 cases, 39 cases (59\%) had a poor visual outcome. Univariate and multivariate Logistic regression analysis identified retained intraocular foreign body (IOFB) as the only factor significantly associated with poor visual outcome [adjusted odds ratio, 4.62; 95\% confidence interval (1.04-20.53); =0.04]. The most common causative agents were gram-positive organisms (83\%), of which (33\%), was the most common pathogen. All cases received intravitreal antibiotic injections. Oral ciprofloxacin was the most used systemic antibiotic (33\%). Pars plana vitrectomy was performed in 83\% (55/66) of cases. At 6mo follow-up, mean BCVA was 1.74{\textpm}0.72 logMAR units. CONCLUSION: In patients with PTE following open globe injury, the only predictor of poor visual outcome is the presence of IOFB. is the most isolated microorganism.},
	issn = {2222-3959},
	doi = {10.18240/ijo.2020.12.19},
	author = {Silpa-Archa, Sukhum and Dejkong, Akkaranisorn and Kumsiang, Kwanchanoke and Chotcomwongse, Peranut and Preble, Janine M and Foster, C Stephen}
}
@article {630251,
	title = {Ocular manifestations in systemic lupus erythematosus.},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {135-41},
	abstract = {Systemic lupus erythematosus (SLE) can involve many parts of the eye, including the eyelid, ocular adnexa, sclera, cornea, uvea, retina and optic nerve. Ocular manifestations of SLE are common and may lead to permanent blindness from the underlying disease or therapeutic side effects. Keratoconjunctivitis sicca is the most common manifestation. However, vision loss may result from involvement of the retina, choroid and optic nerve. Ocular symptoms are correlated to systemic disease activity and can present as an initial manifestation of SLE. The established treatment includes prompt systemic corticosteroids, steroid-sparing immunosuppressive drugs and biological agents. Local ocular therapies are options with promising efficacy. The early recognition of disease and treatment provides reduction of visual morbidity and mortality.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-306629},
	author = {Silpa-Archa, Sukhum and Lee, Joan J and Foster, C Stephen}
}
@article {1263406,
	title = {VITREOUS TREPONEMAL ANTIBODY AS A SUPPLEMENTARY TEST TO SEROLOGY FOR THE CONFIRMATION OF SYPHILITIC CHORIORETINITIS},
	journal = {Retin Cases Brief Rep},
	volume = {14},
	number = {2},
	year = {2020},
	month = {2020 Spring},
	pages = {166-169},
	abstract = {PURPOSE: To report the novel application of nontreponemal and treponemal antibody to confirm diagnosis of ocular syphilis from vitreous samples. METHODS: Two distinct case reports emphasizing the importance of confirmatory vitreous treponemal antibody. Multimodal imaging of patients was also applied. RESULTS: We report two distinct cases with positive serum treponemal antibody but opposing vitreous treponemal antibody results. One case with a positive vitreous test responded well to antisyphilitic treatment. By contrast, a case with a negative vitreous result was changed to serpiginous choroiditis, eventually cured by immunomodulatory treatment. CONCLUSION: Intraocular fluid analysis of nontreponemal and treponemal antibody may play an important role in ruling out suspected ocular syphilis in settings without a polymerase chain reaction facility, especially immunocompromised patients who are at risk of multiple infections. Further studies are needed to establish the sensitivity and specificity of nontreponemal and treponemal antibody test on vitreous samples.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000676},
	author = {Silpa-Archa, Sukhum and Preble, Janine M and Foster, C Stephen}
}
@article {541236,
	title = {Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography.},
	journal = {Ophthalmology},
	volume = {122},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {2465-72},
	abstract = {PURPOSE: To assess whether the presence of peripheral nonperfusion on ultrawide field (UWF) fluorescein angiography (FA) is associated with diabetic retinopathy (DR) severity and the presence of predominantly peripheral lesions (PPLs). DESIGN: Single-site, cross-sectional, retrospective study. PARTICIPANTS: Sixty-eight eyes of 37 diabetic subjects with or without DR and no history of prior panretinal laser photocoagulation. METHODS: Both 200{\textdegree} UWF images and UWF FA images were acquired at the same visit. Early Treatment Diabetic Retinopathy Study (ETDRS) templates were overlaid digitally based on disc and macula location onto stereographically projected UWF images. Images were evaluated for the presence of PPLs, defined as more than 50\% of the graded lesion located outside the ETDRS field in each of the 5 extended fields. The UWF-FA images were evaluated by 2 masked, independent graders for extent of retinal nonperfusion area (NPA) and nonperfusion index (NPI; nonperfused/total gradable area). MAIN OUTCOME MEASURES: Association of NPA and NPI with DR severity and presence of PPLs. RESULTS: Distribution of DR severity was as follows: no DR, 8.8\% eyes; mild nonproliferative DR (NPDR), 17.6\%; moderate NPDR, 32.4\%; severe NPDR, 17.6\%; proliferative DR (PDR), 19.1\%; and high-risk PDR, 4.4\%; with PPL present in 61.8\%. There was strong intragrader (r\&nbsp;= 0.95) and intergrader (r\&nbsp;= 0.86) agreement for NPA. Presence of PPLs was associated with increased NPA (191.8 mm(2) vs. 306.1 mm(2); P\&nbsp;= 0.0019) and NPI (0.25 vs. 0.43; P\&nbsp;= 0.0003). These relationships remained significant after adjusting for DR severity and diabetes duration. In eyes without PDR (n\&nbsp;= 52), increasing NPA and NPI was associated with worsening DR (NPA, P\&nbsp;= 0.001; NPI,\&nbsp;P\&nbsp;= 0.0003). NPA and NPI were not associated with clinically significant macular edema (NPA, P\&nbsp;= 0.99; NPI, P\&nbsp;= 0.67), nor correlated with visual acuity (NPA, r\&nbsp;= 0.14, P\&nbsp;= 0.23; NPI, r\&nbsp;= 0.24, P\&nbsp;= 0.05). CONCLUSIONS: Following a standardized protocol, the evaluation of UWF FA for NPA and NPI is reproducible. Both parameters are correlated highly with the presence of PPLs and DR severity. Given that the presence and extent of PPLs have been associated with increased risks of DR progression, the clinical identification of PPLs may reflect closely the extent of nonperfusion and ischemia, thus accounting for the increased risk of progression.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.07.034},
	author = {Silva, Paolo S and Dela Cruz, Amanda J and Ledesma, Migil G and van Hemert, Jano and Radwan, Ajlan and Cavallerano, Jerry D and Aiello, Lloyd M and Sun, Jennifer K and Aiello, Lloyd Paul}
}
@article {1635660,
	title = {ASSESSMENT OF FLUORESCEIN ANGIOGRAPHY NONPERFUSION IN EYES WITH DIABETIC RETINOPATHY USING ULTRAWIDE FIELD RETINAL IMAGING},
	journal = {Retina},
	volume = {42},
	number = {7},
	year = {2022},
	month = {2022 07 01},
	pages = {1302-1310},
	abstract = {PURPOSE: Evaluate association of retinal nonperfusion (NP) on ultrawide field (UWF) fluorescein angiography (FA) with diabetic retinopathy (DR) severity and predominantly peripheral lesions (PPL). METHODS: Multicenter observational study, 652 eyes (361 participants) having nonproliferative DR (NPDR) without center-involved diabetic macular edema in at least one eye. Baseline 200{\textdegree} UWF-color and UWF-FA images were graded by a central reading center for color-PPL and FA-PPL, respectively. UWF-FA was graded for NP index within concentric zones: posterior pole (\&lt;10 mm from fovea), midperiphery (10-15 mm), and far periphery (\&gt;15 mm). RESULTS: Baseline Early Treatment Diabetic Retinopathy Study DR severity was 31.7\% no DR/mild NPDR, 24.1\% moderate NPDR, 14.0\% moderately severe NPDR, 25.6\% severe/very severe NPDR, and 4.6\% proliferative DR. Worse DR severity was associated with increased NP index overall (P = 0.002), in the posterior pole (P \&lt; 0.001), midperiphery (P \&lt; 0.001), and far periphery (P = 0.03). On average, 29.6\% of imaged retinal NP was in the posterior pole, 33.7\% in midperiphery, and 36.7\% in far periphery. Increased NP index was associated with FA-PPL (P \&lt; 0.001) but not with color-PPL (P = 0.65). CONCLUSION: Approximately, 70\% of NP in diabetic eyes is located outside the posterior pole. Increased NP is associated with the presence of FA-PPL, suggesting UWF-FA may better predict future DR worsening than UWF-color alone.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Fluorescein Angiography, Humans, Macular Edema, Photography, Retina, Retinal Vessels},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003479},
	author = {Silva, Paolo S and Liu, Danni and Glassman, Adam R and Aiello, Lloyd P and Grover, Sandeep and Kingsley, Ronald M and Melia, Michele and Sun, Jennifer K and DRCR Retina Network}
}
@article {1661833,
	title = {Targeted Killing of Ocular Streptococcus pneumoniae by the Phage Endolysin MSlys},
	journal = {Ophthalmol Sci},
	volume = {2},
	number = {4},
	year = {2022},
	month = {2022 Dec},
	pages = {100193},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2022.100193},
	author = {Silva, Maria Daniela and Andr{\'e}, Camille and Bispo, Paulo J M}
}
@article {1137901,
	title = {Ultrawide field scanning laser ophthalmoscopy imaging of lipemia retinalis},
	journal = {Acta Ophthalmol},
	year = {2017},
	month = {2017 Aug 03},
	abstract = {OBJECTIVE: To describe the characteristic retinal features of lipemia retinalis when using ultrawide field scanning laser ophthalmoscopy. MAIN POINTS: We report a case series of three subjects with ultrawide field retinal images showing cream discoloration of the fundus, light salmon-coloured posterior retinal vessels and greyish pink peripheral vasculature. On green-only imaging, many of the vessels appear light rather than typically dark. CONCLUSION: Lipemia retinalis is readily apparent on ultrawide field imaging and illustrates the alterations that systemic diseases may induce in the posterior and peripheral retinal vasculature. Ultrawide field imaging highlights the disparate vascular appearance of the posterior pole and retinal periphery in this condition.},
	issn = {1755-3768},
	doi = {10.1111/aos.13525},
	author = {Silva, Paolo S and Gupta, Aditi and Ajlan, Radwan S and Schlossman, Deborah K and Tolson, Ann M and Cavallerano, Jerry D and Aiello, Lloyd Paul}
}
@article {1363203,
	title = {Peripheral lesions identified by mydriatic ultrawide field imaging: distribution and potential impact on diabetic retinopathy severity},
	journal = {Ophthalmology},
	volume = {120},
	number = {12},
	year = {2013},
	month = {2013 Dec},
	pages = {2587-2595},
	abstract = {OBJECTIVE: To assess diabetic retinopathy (DR) as determined by lesions identified using mydriatic ultrawide field imaging (DiSLO200; Optos plc, Scotland, UK) compared with Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field film photography. DESIGN: Prospective comparative study of DiSLO200, ETDRS 7-standard field film photographs, and dilated fundus examination (DFE). PARTICIPANTS: A total of 206 eyes of 103 diabetic patients selected to represent all levels of DR. METHODS: Subjects had DiSLO200, ETDRS 7-standard field film photographs, and DFE. Images were graded for severity and distribution of DR lesions. Discrepancies were adjudicated, and images were compared side by side. MAIN OUTCOME MEASURES: Distribution of hemorrhage and/or microaneurysm (H/Ma), venous beading (VB), intraretinal microvascular abnormality (IRMA), and new vessels elsewhere (NVE). Kappa (κ) and weighted κ statistics for agreement. RESULTS: The distribution of DR severity by ETDRS 7-standard field film photographs was no DR 12.5\%; nonproliferative DR mild 22.5\%, moderate 30\%, and severe/very severe 8\%; and proliferative DR 27\%. Diabetic retinopathy severity between DiSLO200 and ETDRS film photographs matched in 80\% of eyes (weighted κ = 0.74,κ = 0.84) and was within 1 level in 94.5\% of eyes. DiSLO200 and DFE matched in 58.8\% of eyes (weighted κ = 0.69,κ = 0.47) and were within 1 level in 91.2\% of eyes. Forty eyes (20\%) had DR severity discrepancies between DiSLO200 and ETDRS film photographs. The retinal lesions causing discrepancies were H/Ma 52\%, IRMA 26\%, NVE 17\%, and VB 4\%. Approximately one-third of H/Ma, IRMA, and NVE were predominantly outside ETDRS fields. Lesions identified on DiSLO200 but not ETDRS film photographs suggested a more severe DR level in 10\% of eyes. Distribution in the temporal, superotemporal, inferotemporal, superonasal, and inferonasal fields was 77\%, 72\%, 61\%, 65\%, and 59\% for H/Ma, respectively (P\&lt;0.0001); 22\%, 24\%, 21\%, 28\%, and 22\% for VB, respectively (P = 0.009); 52\%, 40\%, 29\%, 47\%, and 36\% for IRMA, respectively (P\&lt;0.0001), and 8\%, 4\%, 4\%, 8\%, and 5\% for NVE, respectively (P = 0.03). All lesions were more frequent in the temporal fields compared with the nasal fields (P\&lt;0.0001). CONCLUSIONS: DiSLO200 images had substantial agreement with ETDRS film photographs and DFE in determining DR severity. On the basis of DiSLO200 images, significant nonuniform distribution of DR lesions was evident across the retina. The additional peripheral lesions identified by DiSLO200 in this cohort suggested a more severe assessment of DR in 10\% of eyes than was suggested by the lesions within the ETDRS fields. However, the implications of peripheral lesions on DR progression within a specific ETDRS severity level over time are unknown and need to be evaluated prospectively.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Diabetic Retinopathy, Diagnostic Imaging, Drug Combinations, Female, Humans, Male, Middle Aged, Mydriatics, Phenylephrine, Photography, Prospective Studies, Pupil, Retina, Severity of Illness Index, Tropicamide, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2013.05.004},
	author = {Silva, Paolo S and Cavallerano, Jerry D and Sun, Jennifer K and Soliman, Ahmed Z and Aiello, Lloyd M and Aiello, Lloyd Paul}
}
@article {1655722,
	title = {Association of Ultra-Widefield Fluorescein Angiography-Identified Retinal Nonperfusion and the Risk of Diabetic Retinopathy Worsening Over Time},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {10},
	year = {2022},
	month = {2022 Oct 01},
	pages = {936-945},
	abstract = {Importance: Presence of predominantly peripheral diabetic retinopathy (DR) lesions on ultra-widefield fluorescein angiography (UWF-FA) was associated with greater risk of DR worsening or treatment over 4 years. Whether baseline retinal nonperfusion assessment is additionally predictive of DR disease worsening is unclear. Objective: To assess whether the extent and location of retinal nonperfusion identified on UWF-FA are associated with worsening in Diabetic Retinopathy Severity Scale (DRSS) score or DR treatment over time. Design, Setting, and Participants: This cohort study was a prospective, multicenter, longitudinal observational study with data for 508 eyes with nonproliferative DR and gradable nonperfusion on UWF-FA at baseline. All images were graded at a centralized reading center; 200{\textdegree} ultra-widefield (UWF) color images were graded for DR at baseline and annually for 4 years. Baseline 200{\textdegree} UWF-FA images were graded for nonperfused area, nonperfusion index (NPI), and presence of predominantly peripheral lesions on UWF-FA (FA PPL). Interventions: Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures: Association of baseline UWF-FA nonperfusion extent with disease worsening, defined as either 2 or more steps of DRSS worsening within Early Treatment Diabetic Retinopathy Study fields on UWF-color images or receipt of DR treatment. Results: After adjusting for baseline DRSS, the risk of disease worsening over 4 years was higher in eyes with greater overall NPI (hazard ratio [HR] for 0.1-unit increase, 1.11; 95\% CI, 1.02-1.21; P = .02) and NPI within the posterior pole (HR for 0.1-unit increase, 1.35; 95\% CI, 1.17-1.56; P \&lt; .001) and midperiphery (HR for 0.1-unit increase, 1.08; 95\% CI, 1.00-1.16; P = .04). In a multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95\% CI, 1.02-1.22; P = .02) and presence of FA PPL (HR, 1.89; 95\% CI, 1.35-2.65; P \&lt; .001) remained associated with disease worsening. Conclusions and Relevance: This 4-year longitudinal study has demonstrated that both greater baseline retinal nonperfusion and FA PPL on UWF-FA are associated with higher risk of disease worsening, even after adjusting for baseline DRSS score and known systemic risk. These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research.},
	keywords = {Cohort Studies, Diabetes Mellitus, Diabetic Retinopathy, Fluorescein Angiography, Humans, Longitudinal Studies, Macular Edema, Photography, Prospective Studies, Retinal Vessels},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.3130},
	author = {Silva, Paolo S and Marcus, Dennis M and Liu, Danni and Aiello, Lloyd Paul and Antoszyk, Andrew and Elman, Michael and Friedman, Scott and Glassman, Adam R and Googe, Joseph M and Jampol, Lee Merrill and Martin, Daniel F and Melia, Michele and Preston, Carin M and Wykoff, Charles C and Sun, Jennifer K and DRCR Retina Network}
}
@article {469006,
	title = {Real-Time Ultrawide Field Image Evaluation of Retinopathy in a Diabetes Telemedicine Program.},
	journal = {Diabetes Care},
	volume = {38},
	number = {9},
	year = {2015},
	month = {2015 Sep},
	pages = {1643-9},
	abstract = {OBJECTIVE: To evaluate the ability of trained nonphysician retinal imagers to perform diabetic retinopathy (DR) evaluation at the time of ultrawide field retinal (UWF) imaging in a teleophthalmology program. RESEARCH DESIGN AND METHODS: Clinic patients with diabetes received Joslin Vision Network protocol retinal imaging as part of their standard medical care. Retinal imagers evaluated UWF images for referable DR at the time of image capture. Training of the imagers included 4 h of standardized didactic lectures and 12 h of guided image review. Real-time evaluations were compared with standard masked gradings performed at a centralized reading center. RESULTS: A total of 3,978 eyes of 1,989 consecutive patients were imaged and evaluated. By reading center evaluation, 3,769 eyes (94.7\%) were gradable for DR, 1,376 (36.5\%) had DR, and 580 (15.3\%) had referable DR. Compared with the reading center, real-time image evaluation had a sensitivity and specificity for identifying more than minimal DR of 0.95 (95\% CI 0.94-0.97) and 0.84 (0.82-0.85), respectively, and 0.99 (0.97-1.00) and 0.76 (0.75-0.78), respectively, for detecting referable DR. Only three patients with referable DR were not identified by imager evaluation. CONCLUSIONS: Point-of-care evaluation of UWF images by nonphysician imagers following standardized acquisition and evaluation protocols within an established teleophthalmology program had good sensitivity and specificity for detection of DR and for identification of referable retinal disease. With immediate image evaluation, \&lt;0.1\% of patients with referable DR would be missed, reading center image grading burden would be reduced by 60\%, and patient feedback would be expedited.},
	issn = {1935-5548},
	doi = {10.2337/dc15-0161},
	author = {Silva, Paolo S and Cavallerano, Jerry D and Tolson, Ann M and Rodriguez, Jessica and Rodriguez, Sashida and Ajlan, Radwan and Tolls, Dorothy and Patel, Bina and Sehizadeh, Mina and Thakore, Komal and Sun, Jennifer K and Aiello, Lloyd Paul}
}
@article {303986,
	title = {Visual outcomes from pars plana vitrectomy versus combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation in patients with diabetes.},
	journal = {Retina},
	volume = {34},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {1960-8},
	abstract = {PURPOSE: To compare visual acuity outcomes and diabetic retinopathy progression after pars plana vitrectomy (PPV) versus combined pars plana vitrectomy and phacoemulsification (PPVCE) in patients with diabetes. METHODS: Retrospective review of 222 consecutive diabetic patients undergoing PPV or PPVCE. RESULTS: A total of 251 eyes of 222 patients were evaluated (PPV = 122, PPVCE = 129). Four-year follow-up was 64\% (161 eyes). Overall, patients undergoing PPVCE had better preoperative visual acuity (PPVCE = 20/80, PPV = 20/160, P = 0.03). At 4-year follow-up, visual acuity improved (PPV = +22, PPVCE = +11 letters) compared with baseline in both groups. After correcting for baseline differences in visual acuity, no statistically significant difference in final visual acuity was observed (PPVCE = 20/32, PPV = 20/50, P = 0.09). Results did not differ substantially by surgical indication (vitreous hemorrhage, traction retinal detachment, epiretinal membrane, and/or diabetic macular edema). Cataract progression occurred in 64\%, and cataract surgery was performed in 39\% of phakic eyes undergoing PPV. Rates of diabetic retinopathy progression, vitreous hemorrhage, and retinal detachment were not statistically different. Neovascular glaucoma developed in 2 patients (2\%) after PPV and 6 patients (8\%) after PPVCE (P = 0.07). CONCLUSION: In diabetic patients, equivalent visual acuity improvement over 4 years was observed after PPV or PPVCE. Visual outcomes and retinopathy progression rates were not significantly different after either intervention, suggesting that PPVCE may be appropriate when indicated in patients with diabetes.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000171},
	author = {Silva, Paolo S and Diala, Prisca A and Hamam, Rola N and Arrigg, Paul G and Shah, Sabera T and Murtha, Timothy L and Schlossman, Deborah K and Cavallerano, Jerry D and Sun, Jennifer K and Aiello, Lloyd P}
}
@article {669306,
	title = {Identification of Diabetic Retinopathy and Ungradable Image Rate with Ultrawide Field Imaging in a National Teleophthalmology Program.},
	journal = {Ophthalmology},
	volume = {123},
	number = {6},
	year = {2016},
	month = {2016 Jun},
	pages = {1360-7},
	abstract = {PURPOSE: To compare diabetic retinopathy (DR) identification and ungradable image rates between nonmydriatic ultrawide field (UWF) imaging and nonmydriatic multifield fundus photography (NMFP) in a large multistate population-based DR teleophthalmology program. DESIGN: Multiple-site, nonrandomized, consecutive, cross-sectional, retrospective, uncontrolled imaging device evaluation. PARTICIPANTS: Thirty-five thousand fifty-two eyes (17 526 patients) imaged using NMFP and 16 218 eyes (8109 patients) imaged using UWF imaging. METHODS: All patients undergoing Joslin Vision Network (JVN) imaging with either NMFP or UWF imaging from May 1, 2014, through August 30, 2015, within the Indian Health Service-JVN program, which serves American Indian and Alaska Native communities at 97 sites across 25 states, were evaluated. All retinal images were graded using a standardized validated protocol in a centralized reading center. MAIN OUTCOME MEASURES: Ungradable rate for DR and diabetic macular edema (DME). RESULTS: The ungradable rate per patient for DR and DME was significantly lower with UWF imaging compared with NMFP (DR, 2.8\% vs. 26.9\% [P \&lt; 0.0001]; DME, 3.8\% vs. 26.2\% [P \&lt; 0.0001]). Identification of eyes with either DR or referable DR (moderate nonproliferative DR or DME or worse) was increased using UWF imaging from 11.7\% to 24.2\% (P \&lt; 0.0001) and from 6.2\% to 13.6\% (P \&lt; 0.0001), respectively. In eyes with DR imaged with UWF imaging (n\&nbsp;= 3926 eyes of 2402 patients), the presence of predominantly peripheral lesions suggested a more severe level of DR in 7.2\% of eyes (9.6\% of patients). CONCLUSIONS: In a large, widely distributed DR ocular telehealth program, as compared with NMFP, nonmydriatic UWF imaging reduced the number of ungradable eyes by 81\%, increased the identification of DR nearly 2-fold, and identified peripheral lesions suggesting more severe DR in almost 10\% of patients, thus demonstrating significant benefits of this imaging method for large DR teleophthalmology programs.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.01.043},
	author = {Silva, Paolo S and Horton, Mark B and Clary, Dawn and Lewis, Drew G and Sun, Jennifer K and Cavallerano, Jerry D and Aiello, Lloyd Paul}
}
@article {504071,
	title = {Reply.},
	journal = {Retina},
	volume = {35},
	number = {7},
	year = {2015},
	month = {2015 Jul},
	pages = {e37-8},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000640},
	author = {Silva, Paolo S and Aiello, Lloyd Paul}
}
@article {382621,
	title = {Peripheral Lesions Identified on Ultrawide Field Imaging Predict Increased Risk of Diabetic Retinopathy Progression over 4Years.},
	journal = {Ophthalmology},
	volume = {122},
	number = {5},
	year = {2015},
	month = {2015 May},
	pages = {949-56},
	abstract = {OBJECTIVE: To determine whether peripheral diabetic retinopathy (DR) lesions identified on ultrawide field (UWF) imaging are associated with increased DR progression. DESIGN: Prospective, longitudinal cohort. PARTICIPANTS: Two hundred eyes of 100 participants previously enrolled in a comparative instrument validation study. METHODS: Baseline mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and UWF images were obtained. On UWF images, DR lesions with a greater extent outside versus inside standard ETDRS fields were defined as predominantly peripheral lesions (PPLs). Follow-up ETDRS photographs were obtained 4.2{\textpm}0.3 years after baseline. Baseline and follow-up DR severity were graded from ETDRS photographs. MAIN OUTCOME MEASURES: Rates of 2-step or more progression and progression to proliferative DR (PDR) in eyes with PPLs compared with eyes without PPLs identified on UWF imaging at baseline. RESULTS: In eyes without PDR (n\&nbsp;= 109) at baseline, 56 (51\%) had at least 1 field with PPLs and 43 (39\%) had DR progression. Compared with eyes without PPLs, eyes with PPLs had a 3.2-fold increased risk of 2-step or more DR progression (6 [11\%] vs. 19 [34\%]; P\&nbsp;= 0.005) and a 4.7-fold increased risk for progression to PDR (3 [6\%] vs. 14 [25\%]; P\&nbsp;= 0.005). These findings remained statistically significant after adjusting for gender, diabetes type, diabetes duration, hemoglobin A1c (HbA1c) levels, and baseline DR severity. Increasing extent of fields with PPLs increased the risk for 2-step or more DR progression (P\&nbsp;= 0.004) and progression to PDR (P\&nbsp;= 0.009). CONCLUSIONS: Presence and increasing extent of PPLs were associated with increased risk of DR progression over 4 years, independent of baseline DR severity and HbA1c levels. Increasing extent of PPLs substantially increased the risk of DR progression and progression to PDR, especially with less severe DR at baseline. These findings demonstrate that detailed peripheral retinal evaluation provides important information that is necessary to assess completely the risk of DR progression.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.01.008},
	author = {Silva, Paolo S and Cavallerano, Jerry D and Haddad, Nour Maya N and Kwak, Hanna and Dyer, Kelli H and Omar, Ahmed F and Shikari, Hasanain and Aiello, Lloyd M and Sun, Jennifer K and Aiello, Lloyd Paul}
}
@article {1364547,
	title = {Nonmydriatic ultrawide field retinal imaging compared with dilated standard 7-field 35-mm photography and retinal specialist examination for evaluation of diabetic retinopathy},
	journal = {Am J Ophthalmol},
	volume = {154},
	number = {3},
	year = {2012},
	month = {2012 Sep},
	pages = {549-559.e2},
	abstract = {PURPOSE: To compare nonmydriatic stereoscopic Optomap ultrawide field images with dilated stereoscopic Early Treatment Diabetic Retinopathy Study 7-standard field 35-mm color 30-degree fundus photographs (ETDRS photography) and clinical examination for determining diabetic retinopathy (DR) and diabetic macular edema (DME) severity. DESIGN: Single-site, prospective, comparative, instrument validation study. METHODS: One hundred three diabetic patients (206 eyes) representing the full spectrum of DR severity underwent nonmydriatic ultrawide field 100-degree and 200-degree imaging, dilated ETDRS photography, and dilated fundus examination by a retina specialist. Two independent readers graded images to determine DR and DME severity. A third masked retina specialist adjudicated discrepancies. RESULTS: Based on ETDRS photography (n = 200), the results were as follows: no DR (n = 25 eyes [12.5\%]), mild nonproliferative DR (NPDR; 47 [23.5\%]), moderate NPDR (61 [30.5\%]), severe NPDR (11 [5.5\%]), very severe NPDR (3 [1.5\%]), and proliferative DR (52 [2.5\%]). One (0.5\%) eye was ungradable and 6 eyes did not complete ETDRS photography. No DME was found in 114 eyes (57.0\%), DME was found in 28 eyes (14.0\%), and clinically significant DME was found in 47 eyes (23.5\%), and 11 (5.5\%) eyes were ungradable. Exact DR severity agreement between ultrawide field 100-degree imaging and ETDRS photography occurred in 84\%, with agreement within 1 level in 91\% (K(W) = 0.85; K = 0.79). Nonmydriatic ultrawide field images exactly matched clinical examination results for DR in 70\% and were within 1 level in 93\% (K(W) = 0.71; K = 0.61). Nonmydriatic ultrawide field imaging acquisition time was less than half that of dilated ETDRS photography (P \&lt; .0001). CONCLUSIONS: Nonmydriatic ultrawide field images compare favorably with dilated ETDRS photography and dilated fundus examination in determining DR and DME severity; however, they are acquired more rapidly. If confirmed in broader diabetic populations, nonmydriatic ultrawide field imaging may prove to be beneficial in DR evaluation in research and clinical settings.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Humans, Macular Edema, Male, Middle Aged, Mydriatics, Ophthalmology, Photography, Prospective Studies, Pupil, Reproducibility of Results, Retina, Sensitivity and Specificity, Severity of Illness Index, Signal Processing, Computer-Assisted, Specialization, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2012.03.019},
	author = {Silva, Paolo S and Cavallerano, Jerry D and Sun, Jennifer K and Noble, Jason and Aiello, Lloyd M and Aiello, Lloyd Paul}
}
@article {1435409,
	title = {Microvasculature of the Optic Nerve Head and Peripapillary Region in Patients With Primary Open-Angle Glaucoma},
	journal = {J Glaucoma},
	volume = {28},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {281-288},
	abstract = {PURPOSE: To assess optic nerve head (ONH) and peripapillary microvasculature in primary open-angle glaucoma (POAG) of mild to moderate severity using swept-source optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: In a cross-sectional study, swept-source OCTA images were analyzed for 1 eye from each of 30 POAG patients with glaucomatous Humphrey visual field loss and 16 controls. The anatomic boundary of ONH was manually delineated based on Bruch{\textquoteright}s membrane opening and large vessels were removed from en face angiography images to measure vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS), suggestive of flow, in the ONH and peripapillary region. POAG subgroup analysis was performed based on a history of disc hemorrhage (DH) matched by visual field mean deviation (MD). RESULTS: POAG (mean MD{\textpm}SD, -3.3{\textpm}3.0 dB) and control groups had similar demographic characteristics and intraocular pressure on the day of imaging. Groups did not differ in superficial ONH VD or flow indicated by IOS (P>=0.28). POAG eyes showed significantly lower VD (39.4\%{\textpm}4.0\%) and flow (38.8\%{\textpm}5.6\%) in deep ONH, peripapillary VD (37.9\%{\textpm}2.9\%) and flow (43.6\%{\textpm}4.0\%) compared with control eyes (44.1\%{\textpm}5.1\%, 44.7\%{\textpm}6.9\%, 40.7\%{\textpm}1.7\%, 47.8\%{\textpm}2.5\%, respectively; P<=0.007 for all). In the subgroup analysis, POAG eyes with (n=14) and without DH (n=16) had similar measured OCTA parameters (P\&gt;0.99 for all). CONCLUSIONS: The image processing methodology based on the anatomic boundary of ONH demonstrated compromised microvasculature in the deep ONH and peripapillary region in eyes with mild to moderate POAG, regardless of the history of DH.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001165},
	author = {Silva, Rafaella Nascimento E and Chiou, Carolina A and Wang, Mengyu and Wang, Haobing and Shoji, Marissa K and Chou, Jonathan C and D{\textquoteright}Souza, Erica E and Greenstein, Scott H and Brauner, Stacey C and Alves, Milton R and Pasquale, Louis R and Shen, Lucy Q}
}
@article {1445319,
	title = {Glaucoma Management in Patients with Aniridia and Boston Type 1 Keratoprosthesis},
	journal = {Am J Ophthalmol},
	year = {2019},
	month = {2019 Jun 24},
	abstract = {PURPOSE: To assess outcomes and glaucoma management in eyes with aniridia following Boston type 1 Keratoprosthesis (KPro) implantation. DESIGN: Retrospective, interventional comparative case series. METHODS: POPULATION: Patients with aniridia and patients with other preoperative diagnoses (excluding Stevens-Johnson syndrome, mucous membrane pemphigoid, and congenital disorders) who underwent KPro implantation at Massachusetts Eye and Ear with at least 2 years of follow-up. One eye per patient was selected based on the longer follow-up time. MAIN OUTCOME: Intermediate and long-term outcomes related to glaucoma. RESULTS: The aniridia (n=22) and comparison (n=61) groups had similar preoperative visual acuity (VA, mean {\textpm} standard deviation, 1.86{\textpm}0.52 LogMAR, p=0.33) and follow-up time (65.6{\textpm}26.3 months, p=0.25). Prior to KPro implantation, eyes with aniridia had more glaucoma (76.2\%) and glaucoma surgery (57.1\%) than comparison eyes (51.8\%, p=0.053; 23.2\%, p=0.005, respectively). More Ahmed valves were co-implanted with KPro in aniridia (47.6\%) versus comparison eyes (17.9\%, p=0.008). At final follow-up, more aniridia eyes had glaucoma (90.5\%) than comparison eyes (64.3\%, p=0.02), but the two groups had similar percentages of eyes with cup-to-disc ratio (CDR) \&gt;0.8 (23.8\% vs. 30.4\%, p=0.57) or CDR progression of >=0.2 (42.9\% vs. 44.6\%, p=0.89, respectively). None of the eyes with prophylactic tube implantation developed glaucoma. Eyes with and without aniridia did not differ in post-KPro VA improvement (72.7\%, 72.1\%, p=0.96), and final VA (1.28{\textpm}0.79 LogMAR, 1.23{\textpm}0.98 LogMAR, p=0.51). CONCLUSION: Despite a higher glaucoma prevalence, eyes with aniridia achieved similar VA as comparison eyes with more than 5 years of mean follow-up time. Boston KPro offers satisfactory visual rehabilitation in aniridia when glaucoma is managed aggressively.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.06.018},
	author = {Silva, Rafaella Nascimento E and Shen, Lucy Q and Chiou, Carolina A and Shanbhag, Swapna S and Paschalis, Eleftherios I and Pasquale, Louis R and Colby, Kathryn A and Dohlman, Claes H and Chodosh, James and Alves, Milton R}
}
@article {635016,
	title = {Comparison of Nondiabetic Retinal Findings Identified With Nonmydriatic Fundus Photography vs Ultrawide Field Imaging in an Ocular Telehealth Program.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {3},
	year = {2016},
	month = {2016 Mar 1},
	pages = {330-4},
	abstract = {IMPORTANCE: Ultrawide field imaging (UWFI) is increasingly being used in teleophthalmology settings. Given the greater area of the retina imaged, we evaluated the ability of UWFI vs nonmydriatic fundus photography (NMFP) to detect nondiabetic retinal findings in a teleophthalmology program. OBSERVATION: We conducted a retrospective single-center comparative cohort study from January 1, 2011, to June 30, 2013, imaging 3864 and 3971 consecutive teleophthalmology patients (7728 and 7942 eyes) using NMFP and UWFI, respectively. Standard diabetic retinopathy evaluation and nondiabetic findings were compared between the 2 imaging modalities. In patients without diabetic retinopathy (2243 by NMFP and 2252 by UWFI), the rate of identification of nondiabetic findings by NMFP (451 patients [20.1\%]) and UWFI (490 [21.8\%]) were comparable (P = .19). Ultrawide field imaging increased the identification of choroidal nevi by 27\% (406 eyes [5.3\%] by NMFP vs 545 eyes [6.9\%] by UWFI; P \&lt; .001) and chorioretinal atrophy or scarring by 116\% (50 eyes [0.6\%] by NMFP vs 101 eyes [1.3\%] by UWFI; P \&lt; .001). No peripheral retinal findings were identified with NMFP, while UWFI detected 25 retinal tears (0.3\%; P \&lt; .001), 54 lattice and peripheral degenerations (0.7\%; P \&lt; .001), and 142 cases of vitreous detachment or floaters (1.8\%; P \&lt; .001). Data analysis was performed from November 1, 2013, to May 1, 2014. CONCLUSIONS AND RELEVANCE: In eyes without diabetic retinopathy, approximately 20\% may have ocular findings identified on retinal imaging, which emphasizes the role of retinal imaging in patients with diabetes mellitus type 1 and type 2 regardless of the severity of retinopathy. In this cohort, UWFI increased the identification of peripheral retinal and vitreous pathologic findings.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.5605},
	author = {Silva, Paolo S and Cavallerano, Jerry D and Haddad, Nour Maya N and Tolls, Dorothy and Thakore, Komal and Patel, Bina and Sehizadeh, Mina and Tolson, Ann M and Sun, Jennifer K and Aiello, Lloyd Paul}
}
@article {1806566,
	title = {Automated Machine Learning for Predicting Diabetic Retinopathy Progression From Ultra-Widefield Retinal Images},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {171-177},
	abstract = {IMPORTANCE: Machine learning (ML) algorithms have the potential to identify eyes with early diabetic retinopathy (DR) at increased risk for disease progression. OBJECTIVE: To create and validate automated ML models (autoML) for DR progression from ultra-widefield (UWF) retinal images. DESIGN, SETTING AND PARTICIPANTS: Deidentified UWF images with mild or moderate nonproliferative DR (NPDR) with 3 years of longitudinal follow-up retinal imaging or evidence of progression within 3 years were used to develop automated ML models for predicting DR progression in UWF images. All images were collected from a tertiary diabetes-specific medical center retinal image dataset. Data were collected from July to September 2022. EXPOSURE: Automated ML models were generated from baseline on-axis 200{\textdegree} UWF retinal images. Baseline retinal images were labeled for progression based on centralized reading center evaluation of baseline and follow-up images according to the clinical Early Treatment Diabetic Retinopathy Study severity scale. Images for model development were split 8-1-1 for training, optimization, and testing to detect 1 or more steps of DR progression. Validation was performed using a 328-image set from the same patient population not used in model development. MAIN OUTCOMES AND MEASURES: Area under the precision-recall curve (AUPRC), sensitivity, specificity, and accuracy. RESULTS: A total of 1179 deidentified UWF images with mild (380 [32.2\%]) or moderate (799 [67.8\%]) NPDR were included. DR progression was present in half of the training set (590 of 1179 [50.0\%]). The model{\textquoteright}s AUPRC was 0.717 for baseline mild NPDR and 0.863 for moderate NPDR. On the validation set for eyes with mild NPDR, sensitivity was 0.72 (95\% CI, 0.57-0.83), specificity was 0.63 (95\% CI, 0.57-0.69), prevalence was 0.15 (95\% CI, 0.12-0.20), and accuracy was 64.3\%; for eyes with moderate NPDR, sensitivity was 0.80 (95\% CI, 0.70-0.87), specificity was 0.72 (95\% CI, 0.66-0.76), prevalence was 0.22 (95\% CI, 0.19-0.27), and accuracy was 73.8\%. In the validation set, 6 of 9 eyes (75\%) with mild NPDR and 35 of 41 eyes (85\%) with moderate NPDR progressed 2 steps or more were identified. All 4 eyes with mild NPDR that progressed within 6 months and 1 year were identified, and 8 of 9 (89\%) and 17 of 20 (85\%) with moderate NPDR that progressed within 6 months and 1 year, respectively, were identified. CONCLUSIONS AND RELEVANCE: This study demonstrates the accuracy and feasibility of automated ML models for identifying DR progression developed using UWF images, especially for prediction of 2-step or greater DR progression within 1 year. Potentially, the use of ML algorithms may refine the risk of disease progression and identify those at highest short-term risk, thus reducing costs and improving vision-related outcomes.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Disease Progression, Eye, Humans},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.6318},
	author = {Silva, Paolo S and Zhang, Dean and Jacoba, Cris Martin P and Fickweiler, Ward and Lewis, Drew and Leitmeyer, Jeremy and Curran, Katie and Salongcay, Recivall P and Doan, Duy and Ashraf, Mohamed and Cavallerano, Jerry D and Sun, Jennifer K and Peto, Tunde and Aiello, Lloyd Paul}
}
@article {382441,
	title = {Telemedicine and eye examinations for diabetic retinopathy: a time to maximize real-world outcomes.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {5},
	year = {2015},
	month = {2015 May 1},
	pages = {525-6},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.0333},
	author = {Silva, Paolo S and Aiello, Lloyd Paul}
}
@article {1043271,
	title = {Hemorrhage and/or Microaneurysm Severity and Count in Ultrawide Field Images and Early Treatment Diabetic Retinopathy Study Photography},
	journal = {Ophthalmology},
	volume = {124},
	number = {7},
	year = {2017},
	month = {2017 Jul},
	pages = {970-976},
	abstract = {OBJECTIVE: To evaluate detection of hemorrhage and/or microaneurysm (H/Ma) using ultrawide field (UWF) retinal imaging as compared with standard Early Treatment Diabetic Retinopathy Study (ETDRS) 7-field photographs (ETDRS photos). DESIGN: Single-site comparative study of UWF images and ETDRS photos. PARTICIPANTS: One hundred twenty-six eyes of 69 patients with no diabetic retinopathy (DR) or mild or moderate nonproliferative DR (NPDR). METHODS: Stereoscopic 200{\textdegree} UWF images and stereoscopic 35mm 30{\textdegree} 7-field color photographs were acquired on the same visit. Images were graded for severity and distribution of H/Ma. H/Mas were counted in ETDRS fields 2 to 7 in both ETDRS photos and UWF images. H/Mas in the UWF peripheral fields were also counted. MAIN OUTCOME MEASURES: Kappa (κ) and weighted κ statistics for agreement. Number of H/Ma within and outside ETDRS fields identified in UWF images and ETDRS photos. RESULTS: Distribution of DR severity by ETDRS photos was 24 (19.0\%) no DR, 48 (38.1\%) mild NPDR, and 54 (42.9\%) moderate NPDR. A total of 748 of 756 fields (98.9\%) were gradable for H/Mas on ETDRS photos and UWF images. Simple κ/weighted κ statistics for severity of H/Ma: all fields 0.61/0.69, field 2 0.70/0.77, field 3\&nbsp;0.62/0.73, field 4 0.50/0.62, field 5 0.54/0.65, field 6 0.64/0.70, and field 7 0.58/0.63 with overall exact agreement in 81.3\% and within 1 step in 97.9\% of fields. A greater proportion of fields was graded a more severe H/Ma level in UWF images than in the corresponding ETDRS photos (UWF: 12.7\% vs. ETDRS: 6.5\%). Evaluating comparable areas in UWF images and ETDRS photos (fields 2-7), a mean of 42.8 H/Mas were identified using\&nbsp;ETDRS photos and 48.8 in UWF images (P\&nbsp;= 0.10). An additional mean of 21.3 H/Mas (49.8\% increase, P\&nbsp;\&lt;\&nbsp;0.0001) were identified in the peripheral fields of the UWF images. CONCLUSIONS: There is good to excellent agreement between UWF images and ETDRS photos in determining H/Ma severity, with excellent correlation of H/Ma counts within ETDRS photo fields. UWF peripheral fields identified 49.8\% more H/Ma, suggesting a more severe H/Ma in 12.7\% of eyes. Given the additional lesions detected in peripheral fields and the known risks associated with H/Ma and peripheral lesions, quantification of H/Ma using UWF images may provide a more accurate representation of DR disease activity and potential greater accuracy in predicting DR progression.},
	keywords = {Diabetic Retinopathy, Disease Progression, Follow-Up Studies, Humans, Microaneurysm, Photography, Prospective Studies, Retina, Retinal Hemorrhage, ROC Curve, Severity of Illness Index, Time Factors},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.02.012},
	author = {Silva, Paolo S and El-Rami, Hala and Barham, Rasha and Gupta, Aditi and Fleming, Alan and van Hemert, Jano and Cavallerano, Jerry D and Sun, Jennifer K and Aiello, Lloyd Paul}
}
@article {1538321,
	title = {Quantification of the Peripapillary Microvasculature in Eyes with Glaucomatous Paracentral Visual Field Loss},
	journal = {Ophthalmol Glaucoma},
	volume = {4},
	number = {3},
	year = {2021},
	month = {2021 May-Jun},
	pages = {286-294},
	abstract = {PURPOSE: To quantify abnormalities in the peripapillary microvasculature in eyes with primary open-angle glaucoma (POAG) and paracentral visual field (VF) loss. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Thirty-three POAG patients, including 15 with paracentral VF loss and 18 with peripheral VF loss, and 31 control participants underwent swept-source OCT angiography (OCTA) of the peripapillary region. METHODS: The POAG groups were matched by VF mean deviation (MD). The peripapillary microvasculature from the internal limiting membrane to the retinal nerve fiber layer (RNFL) interface was quantified within a 0.70-mm annulus around Bruch{\textquoteright}s membrane opening after removal of large vessels. Both vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS) suggestive of flow were measured. Regional VD and IOS were measured from the affected hemisphere corresponding to the VF hemifield of more severe loss, which was used to calculate the paracentral total deviation (PaTD), or total deviation within the central 10{\textdegree}. One eye per participant was included. MAIN OUTCOME MEASURES: Difference in peripapillary OCTA measurements between paracentral and peripheral VF loss groups and correlation of peripapillary VD and IOS with PaTD. RESULTS: The POAG groups had matched VF MD (-3.1 {\textpm} 2.5 dB paracentral vs. -2.3 {\textpm} 2.0 dB peripheral; P\&nbsp;= 0.31), did not differ in average RNFL thickness (71.1 {\textpm} 14.7 μm vs. 78.1 {\textpm} 15.0 μm; P\&nbsp;= 0.55), but differed in age (59.2 {\textpm} 9.6 years paracentral vs. 67.4 {\textpm} 6.6 years peripheral; P\&nbsp;= 0.02). Compared with control participants, both paracentral and peripheral VF loss groups showed reduced VD (P \&lt; 0.001 and P\&nbsp;= 0.009, respectively) and IOS (P \&lt; 0.001 and P\&nbsp;= 0.01, respectively) in the affected hemisphere. Compared with POAG eyes with peripheral VF loss, the paracentral group showed reduced peripapillary VD (38.0 {\textpm} 2.0\%, 35.0 {\textpm} 2.2\%, respectively; P\&nbsp;= 0.001) and IOS (44.3 {\textpm} 3.1\%, 40.4 {\textpm} 4.0\%, respectively; P\&nbsp;= 0.02) in the affected hemisphere. Among all POAG eyes, peripapillary VD and IOS of the affected hemisphere correlated significantly with functional measurement of paracentral loss (PaTD, r\&nbsp;= 0.40, P\&nbsp;= 0.02; r\&nbsp;= 0.45, P\&nbsp;= 0.008; respectively). These correlations remained significant after adjusting for age (r\&nbsp;= 0.41, P\&nbsp;= 0.02; r\&nbsp;= 0.47, P\&nbsp;= 0.01; respectively). CONCLUSIONS: Regional peripapillary microvasculature showed decreased VD and flow in POAG with paracentral loss, supporting its importance in this glaucoma subtype.},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2020.10.009},
	author = {Silva, Rafaella Nascimento E and Chiou, Carolina A and Wang, Mengyu and Devlin, Julia and Li, Dian and Lovelace, Sydney and Wang, Haobing and Greenstein, Scott H and Brauner, Stacey C and Shen, Lucy Q}
}
@article {1474189,
	title = {Angle Anatomy and Glaucoma in Patients With Boston Keratoprosthesis},
	journal = {Cornea},
	volume = {39},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {713-719},
	abstract = {PURPOSE: To quantitatively analyze the angle anatomy in eyes with a Boston type 1 keratoprosthesis (KPro) using anterior segment optical coherence tomography (AS-OCT) and to assess the diagnostic ability of AS-OCT in KPro-associated glaucoma. METHODS: AS-OCT (RTVue) images from KPro eyes with and without glaucoma were reviewed. The angle opening distance at 500 μm from the scleral spur (AOD500), trabecular-iris angle at 500 μm from the scleral spur (TIA500), and trabecular-iris surface area at 500 μm from the scleral spur (TISA500) were measured by 2 observers masked to the diagnosis. The measurements for each visible quadrant were compared between KPro eyes with and without glaucoma. RESULTS: Twenty-two eyes with glaucoma and 17 eyes without glaucoma from 39 patients with KPro were included. Of the 4 quadrants imaged, the temporal angle was the most visible (79.5\%) and angle measurements of the temporal quadrant were the only ones that differentiated the 2 groups: the mean AOD500, TIA500, and TISA500 were significantly lower in KPro eyes with glaucoma than without glaucoma (388.2 {\textpm} 234.4 μm vs. 624.5 {\textpm} 310.5 μm, P = 0.02; 26.1 {\textpm} 14.0 degrees vs. 39.1 {\textpm} 17.1 degrees, P = 0.03; and 0.15 {\textpm} 0.09 mm vs. 0.23 {\textpm} 0.12 mm, P = 0.03; respectively). The highest area under the receiver operating characteristic curve for detecting glaucoma was 0.75 for temporal TIA500 (95\% confidence interval 0.57-0.94, P = 0.02) with 50\% specificity at 80\% of sensitivity and a cutoff value of 37 degrees. CONCLUSIONS: The temporal angle was the most visible on AS-OCT in eyes with a KPro. Significant narrowing of the temporal angle detected on AS-OCT was associated with glaucoma in these eyes.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002216},
	author = {Silva, Rafaella Nascimento E and Taniguchi, Elise V and Cruzat, Andrea and Paschalis, Eleftherios I and Pasquale, Louis R and Colby, Kathryn A and Dohlman, Claes H and Chodosh, James and Shen, Lucy Q}
}
@article {1109791,
	title = {Fgf8 Expression and Degradation of Retinoic Acid Are Required for Patterning a High-Acuity Area in the Retina},
	journal = {Dev Cell},
	volume = {42},
	number = {1},
	year = {2017},
	month = {2017 Jul 10},
	pages = {68-81.e6},
	abstract = {Species that are highly reliant on their visual system have a specialized retinal area subserving high-acuity vision, e.g., the fovea in humans. Although of critical importance for our daily activities, little is known about the mechanisms driving the development of retinal high-acuity areas (HAAs). Using the chick as a model, we found a precise and dynamic expression pattern of fibroblast growth factor 8 (Fgf8) in the HAA anlage, which was regulated by enzymes that degrade retinoic acid (RA). Transient manipulation of RA signaling, or reduction of Fgf8 expression, disrupted several features of HAA patterning, including photoreceptor distribution, ganglion cell density, and organization of interneurons. Notably, patterned expression of RA signaling components was also found in humans, suggesting that RA also plays a role in setting up the human fovea.},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2017.05.024},
	author = {da Silva, Susana and Cepko, Constance L}
}
@article {382446,
	title = {Automated retinal image analysis for diabetic retinopathy in telemedicine.},
	journal = {Curr Diab Rep},
	volume = {15},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {14},
	abstract = {There will be an estimated 552 million persons with diabetes globally by the year 2030. Over half of these individuals will develop diabetic retinopathy, representing a nearly insurmountable burden for providing diabetes eye care. Telemedicine programmes have the capability to distribute quality eye care to virtually any location and address the lack of access to ophthalmic services. In most programmes, there is currently a heavy reliance on specially trained retinal image graders, a resource in short supply worldwide. These factors necessitate an image grading automation process to increase the speed of retinal image evaluation while maintaining accuracy and cost effectiveness. Several automatic retinal image analysis systems designed for use in telemedicine have recently become commercially available. Such systems have the potential to substantially improve the manner by which diabetes eye care is delivered by providing automated real-time evaluation to expedite diagnosis and referral if required. Furthermore, integration with electronic medical records may allow a more accurate prognostication for individual patients and may provide predictive modelling of medical risk factors based on broad population data.},
	issn = {1539-0829},
	doi = {10.1007/s11892-015-0577-6},
	author = {Sim, Dawn A and Keane, Pearse A and Tufail, Adnan and Egan, Catherine A and Aiello, Lloyd Paul and Silva, Paolo S}
}
@article {988016,
	title = {Diagnostic Capability of Peripapillary Retinal Volume Measurements in Glaucoma},
	journal = {J Glaucoma},
	volume = {26},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {592-601},
	abstract = {PURPOSE: To determine the diagnostic capability of spectral domain optical coherence tomography peripapillary retinal volume (RV) measurements. MATERIALS AND METHODS: A total of 156 patients, 89 primary open-angle glaucoma and 67 normal subjects, were recruited. Spectral domain optical coherence tomography peripapillary RV was calculated for 4 quadrants using 3 annuli of varying scan circle diameters: outer circumpapillary annuli of circular grids 1, 2, and 3 (OCA1, OCA2, OCA3). Area under the receiver operating characteristic curves and pairwise comparisons of receiver operating characteristic (ROC) curves were performed to determine which quadrants were best for diagnosing primary open-angle glaucoma. The pairwise comparisons of the best ROC curves for RV and retinal nerve fiber layer (RNFL) were performed. The artifact rates were analyzed. RESULTS: Pairwise comparisons showed that the smaller annuli OCA1 and OCA2 had better diagnostic performance than the largest annulus OCA3 (P\&lt;0.05 for all quadrants). OCA1 and OCA2 had similar diagnostic performance, except for the inferior quadrant which was better for OCA1 (P=0.0033). The pairwise comparisons of the best ROC curves for RV and RNFL were not statistically significant. RV measurements had lower rates of artifacts at 7.4\% while RNFL measurements had higher rates at 42.9\%. CONCLUSIONS: Peripapillary RV measurements have excellent ability for diagnosing not only glaucoma patients but also a subset of early glaucoma patients. The inferior quadrant of peripapillary annulus OCA1 demonstrated the best diagnostic capability for both glaucoma and early glaucoma. The diagnostic ability of RV is comparable with that of RNFL parameters in glaucoma but with lower artifact rates.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000621},
	author = {Simavli, Huseyin and Poon, Linda Yi-Chieh and Que, Christian J and Liu, Yingna and Akduman, Mustafa and Tsikata, Edem and de Boer, Johannes F and Chen, Teresa C}
}
@article {341671,
	title = {Diagnostic capability of peripapillary retinal thickness in glaucoma using 3D volume scans.},
	journal = {Am J Ophthalmol},
	volume = {159},
	number = {3},
	year = {2015},
	month = {2015 Mar},
	pages = {545-56.e2},
	abstract = {PURPOSE: To determine the diagnostic capability of spectral-domain optical coherence tomography (SD OCT) peripapillary retinal thickness (RT) measurements from 3-dimensional (3D) volume scans for primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study. METHODS: setting: Institutional. study population: 156 patients (89 POAG and 67 normal subjects). observation procedures: One eye of each subject was included. SD OCT peripapillary RT values from 3D volume scans were calculated for 4 quadrants of 3 different sized annuli. Peripapillary retinal nerve fiber layer (RNFL) thickness values were also determined. main outcome measures: Area under the receiver operating characteristic curve (AUROC) values, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. RESULTS: The top 5 RT AUROCs for all glaucoma patients and for a subset of early glaucoma patients were for the inferior quadrant of outer circumpapillary annulus of circular grid (OCA) 1 (0.959, 0.939), inferior quadrant of OCA2 (0.945, 0.921), superior quadrant of OCA1 (0.890, 0.811), inferior quadrant of OCA3 (0.887, 0.854), and superior quadrant of OCA2 (0.879, 0.807). Smaller RT annuli OCA1 and OCA2 consistently showed better diagnostic performance than the larger RT annulus OCA3. For both RNFL and RT measurements, best AUROC values were found for inferior RT OCA1 and OCA2, followed by inferior and overall RNFL thickness. CONCLUSION: Peripapillary RT measurements from 3D volume scans showed excellent diagnostic performance for detecting both glaucoma and early glaucoma patients. Peripapillary RT values have the same or better diagnostic capability compared to peripapillary RNFL thickness measurements, while also having fewer algorithm errors.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.12.004},
	author = {Simavli, Huseyin and Que, Christian John and Akduman, Mustafa and Rizzo, Jennifer L and Tsikata, Edem and de Boer, Johannes F and Chen, Teresa C}
}
@article {1629466,
	title = {Genome-Wide Association Study Identifies Two Common Loci Associated with Pigment Dispersion Syndrome/Pigmentary Glaucoma and Implicates Myopia in its Development},
	journal = {Ophthalmology},
	volume = {129},
	number = {6},
	year = {2022},
	month = {2022 06},
	pages = {626-636},
	abstract = {PURPOSE: To identify genetic variants associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) in unrelated patients and to further understand the genetic and potentially causal relationships between PDS and associated risk factors. DESIGN: A 2-stage genome-wide association meta-analysis with replication and subsequent in silico analyses including Mendelian randomization. PARTICIPANTS: A total of 574 cases with PG or PDS and 52 627 controls of European descent. METHODS: Genome-wide association analyses were performed in 4 cohorts and meta-analyzed in 3 stages: (1) a discovery meta-analysis was performed in 3 cohorts, (2) replication was performed in the fourth cohort, and (3) all 4 cohorts were meta-analyzed to increase statistical power. Two-sample Mendelian randomization was used to determine whether refractive error and intraocular pressure exert causal effects over PDS. MAIN OUTCOME MEASURES: The association of genetic variants with PDS and whether myopia exerts causal effects over PDS. RESULTS: Significant association was present at 2 novel loci for PDS/PG. These loci and follow-up analyses implicate the genes gamma secretase activator protein (GSAP) (lead single nucleotide polymorphism [SNP]: rs9641220, P\&nbsp;= 6.0{\texttimes}10-10) and glutamate metabotropic receptor 5 (GRM5)/TYR (lead SNP: rs661177, P\&nbsp;= 3.9{\texttimes}10-9) as important factors in disease risk. Mendelian randomization showed significant evidence that negative refractive error (myopia) exerts a direct causal effect over PDS (P\&nbsp;= 8.86{\texttimes}10-7). CONCLUSIONS: Common SNPs relating to the GSAP and GRM5/TYR genes are associated risk factors for the development of PDS and PG. Although myopia is a known risk factor, this study uses genetic data to demonstrate that myopia is, in part, a cause of PDS and PG.},
	keywords = {Genome-Wide Association Study, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Myopia, Polymorphism, Single Nucleotide},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.01.005},
	author = {Simcoe, Mark J and Shah, Ameet and Fan, Bao Jian and Choquet, H{\'e}l{\`e}ne and Weisschuh, Nicole and Waseem, Naushin H and Jiang, Chen and Melles, Ronald B and Ritch, Robert and Mahroo, Omar A and Wissinger, Bernd and Jorgenson, Eric and Wiggs, Janey L and Garway-Heath, David F and Hysi, Pirro G and Hammond, Christopher J}
}
@article {1466908,
	title = {Older age and larger cyst size in children with spontaneous rupture of periorbital dermoid cysts},
	journal = {J AAPOS},
	year = {2019},
	month = {2019 Sep 11},
	abstract = {We analyzed clinical and histopathologic data of 97 pediatric patients who underwent excision of dermoid cysts. On review, 16.5\% of the sample population demonstrated localized chronic inflammatory changes, including the presence of giant cells and epithelial disruption. These features were considered indicative of prior cyst rupture. Age at time of initial presentation was significantly older and cyst size was significantly larger in patients with histopathologic signs of previous rupture. Longer time to presentation and time to excision were associated with increased odds of spontaneous rupture.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.06.006},
	author = {Simmons, Nathaniel L and Robb, Richard M and Tybor, David J and Gilbert, Aubrey L}
}
@article {382241,
	title = {Achieving target refraction after cataract surgery.},
	journal = {Ophthalmology},
	volume = {121},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {440-4},
	abstract = {PURPOSE: To evaluate the difference between target and actual refraction after phacoemulsification and intraocular lens implantation at an academic teaching institution{\textquoteright}s Comprehensive Ophthalmology Service.

DESIGN: Retrospective study.

PARTICIPANTS: We examined 1275 eye surgeries for this study.

METHODS: All consecutive cataract surgeries were included if they were performed by an attending or resident surgeon from January through December 2010. Postoperative refractions were compared with preoperative target refractions. Patients were excluded if they did not have a preoperative target refraction documented or if they did not have a recorded postoperative manifest refraction within 90 days.

MAIN OUTCOME MEASURES: The main outcome measure was percentage of cases achieving a postoperative spherical equivalent {\textpm} 1.0 diopter (D) of target spherical equivalent.

RESULTS: We performed 1368 cataract surgeries from January through December of 2010. Of these, 1275 (93\%) had sufficient information for analysis. Of the included cases, 94\% (1196 of 1275) achieved {\textpm} 1.0 D of target refraction by 90 days after cataract surgery.

CONCLUSIONS: This paper establishes a new benchmark for a teaching hospital, where 94\% of patients achieved within 1.0 D of target refraction after cataract surgery. The refractive outcomes after cataract surgery at this academic teaching institution were higher than average international benchmarks.},
	keywords = {Adult, Aged, Aged, 80 and over, Benchmarking, Female, Hospitals, Teaching, Humans, Lens Implantation, Intraocular, Lenses, Intraocular, Male, Middle Aged, Phacoemulsification, Postoperative Period, Pseudophakia, Refraction, Ocular, Retrospective Studies, Treatment Outcome, Visual Acuity},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2013.09.022},
	author = {Simon, Shira S and Chee, Yewlin E and Haddadin, Ramez I and Veldman, Peter B and Borboli-Gerogiannis, Sheila and Brauner, Stacey C and Chang, Kenneth K and Chen, Sherleen H and Gardiner, Matthew F and Greenstein, Scott H and Kloek, Carolyn E and Chen, Teresa C}
}
@article {1645474,
	title = {Electron-Beam Irradiated Recombinant Human Collagen-Phosphorylcholine Corneal Implants Retain Pro-Regeneration Capacity},
	journal = {Front Bioeng Biotechnol},
	volume = {10},
	year = {2022},
	month = {2022},
	pages = {883977},
	abstract = {Sterilization of biodegradable, collagen-based implants is challenging as irradiation sterilization methods can alter their mechanical properties. Electron beam (EB) irradiation is a terminal sterilization method that has been used for biologically-derived implants. Here, recombinant human collagen type III-phosphorylcholine (RHCIII-MPC) hydrogels were irradiated with EB doses of 17, 19, or 21\&nbsp;kGy and their subsequent biocompatibility and ability to promote regeneration in rabbit corneas was evaluated. Unirradiated hydrogels stored in 1\% chloroform in phosphate-buffered saline (C-PBS) were the controls. There were no significant differences between irradiated and non-irradiated samples in optical or physical properties (tensile strength, modulus, elasticity), or the ability to support cell growth. However, irradiated implants were more sensitive to high levels of collagenase than unirradiated controls and the C-PBS implants had increased cell growth compared to EB and controls at 72\&nbsp;h. Corneal implants e-beamed at 17\&nbsp;kGy or e-beamed and subsequently frozen (EB-F) to increase shelf-life showed no adverse biological effects of the irradiation. EB, EB-F, and C-PBS implanted corneas all rapidly re-epithelialized but showed mild neovascularization that resolved over 6\&nbsp;months. The regenerated neo-corneas were transparent at 6\&nbsp;months post-operation. In vivo confocal microscopy confirmed normal morphology for the epithelium, stroma, sub-basal nerves and unoperated endothelium. Histology showed that all the regenerated corneas were morphologically similar to the normal. Immunohistochemistry indicated the presence of a differentiated corneal epithelium and functional tear film. In conclusion, the e-beamed corneal implants performed as well as non-irradiated control implants, resulting in fully regenerated neo-corneas with new nerves and without blood vessels or inflammation that may impede vision or corneal function. Therefore, a complete validation study to establish EB irradiation as an effective means for corneal implant sterilization prior to clinical application is necessary as a next step.},
	issn = {2296-4185},
	doi = {10.3389/fbioe.2022.883977},
	author = {Simpson, Fiona C and Islam, Mohammed Mirazul and Buznyk, Oleksiy and Edin, Elle and Groleau, Marc and Kozak-Ljunggren, Monika and Magrelli, Federica M and AbuSamra, Dina B and Arg{\"u}eso, Pablo and Chodosh, James and Liszka, Aneta and Fagerholm, Per and Griffith, May}
}
@article {1593833,
	title = {Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs},
	journal = {Commun Biol},
	volume = {4},
	number = {1},
	year = {2021},
	month = {2021 May 21},
	pages = {608},
	abstract = {The long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants can be manufactured from a collagen analog (collagen-like peptide-polyethylene glycol hybrid, CLP-PEG) and inflammation-suppressing polymeric 2-methacryloyloxyethyl phosphorylcholine (MPC) when stabilized with the triazine-based crosslinker 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The resulting CLP-PEG-MPC implants led to reduced corneal swelling, haze, and neovascularization in comparison to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. Implants incorporating MPC allowed for faster nerve regeneration and recovery of corneal sensation. CLP-PEG-MPC implants appear to be at a more advanced stage of regeneration than the CLP-PEG only implants, as evidenced by the presence of higher amounts of cornea-specific type V collagen, and a corresponding decrease in the presence of extracellular vesicles and exosomes in the corneal stroma, in keeping with the amounts present in healthy, unoperated corneas.},
	issn = {2399-3642},
	doi = {10.1038/s42003-021-02108-y},
	author = {Simpson, Fiona C and McTiernan, Christopher D and Islam, Mohammad Mirazul and Buznyk, Oleksiy and Lewis, Philip N and Meek, Keith M and Haagdorens, Michel and Audiger, Cindy and Lesage, Sylvie and Gueriot, Fran{\c c}ois-Xavier and Brunette, Isabelle and Robert, Marie-Claude and Olsen, David and Koivusalo, Laura and Liszka, Aneta and Fagerholm, Per and Gonzalez-Andrades, Miguel and Griffith, May}
}
@article {1351189,
	title = {Short temporal asynchrony disrupts visual object recognition},
	journal = {J Vis},
	volume = {14},
	number = {5},
	year = {2014},
	month = {2014 May 12},
	pages = {7},
	abstract = {Humans can recognize objects and scenes in a small fraction of a second. The cascade of signals underlying rapid recognition might be disrupted by temporally jittering different parts of complex objects. Here we investigated the time course over which shape information can be integrated to allow for recognition of complex objects. We presented fragments of object images in an asynchronous fashion and behaviorally evaluated categorization performance. We observed that visual recognition was significantly disrupted by asynchronies of approximately 30 ms, suggesting that spatiotemporal integration begins to break down with even small deviations from simultaneity. However, moderate temporal asynchrony did not completely obliterate recognition; in fact, integration of visual shape information persisted even with an asynchrony of 100 ms. We describe the data with a concise model based on the dynamic reduction of uncertainty about what image was presented. These results emphasize the importance of timing in visual processing and provide strong constraints for the development of dynamical models of visual shape recognition.},
	keywords = {Adult, Female, Form Perception, Humans, Male, Pattern Recognition, Visual, Psychophysics, Time Factors, Vision, Ocular, Visual Pathways, Young Adult},
	issn = {1534-7362},
	doi = {10.1167/14.5.7},
	author = {Singer, Jedediah M and Kreiman, Gabriel}
}
@article {1528432,
	title = {Salivary and lacrimal dysfunction after radioactive iodine for differentiated thyroid cancer: American Head and Neck Society Endocrine Surgery Section and Salivary Gland Section joint multidisciplinary clinical consensus statement of otolaryngology, ophth},
	journal = {Head Neck},
	year = {2020},
	month = {2020 Aug 19},
	abstract = {BACKGROUND: Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement. METHODS: A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations. RESULTS: Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management. CONCLUSION: Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.},
	issn = {1097-0347},
	doi = {10.1002/hed.26417},
	author = {Singer, Michael C and Marchal, Francis and Angelos, Peter and Bernet, Vic and Boucai, Laura and Buchholzer, Samanta and Burkey, Brian and Eisele, David and Erkul, Evren and Faure, Frederic and Freitag, Suzanne K and Gillespie, Marion Boyd and Harrell, Richard Mack and Hartl, Dana and Haymart, Megan and Leffert, Jonathan and Mandel, Susan and Miller, Barbra S and Morris, John and Pearce, Elizabeth N and Rahmati, Rahmatullah and Ryan, William R and Schaitkin, Barry and Schlumberger, Martin and Stack, Brendan C and Van Nostrand, Doug and Wong, Ka Kit and Randolph, Gregory}
}
@article {382626,
	title = {Sensitivity to timing and order in human visual cortex.},
	journal = {J Neurophysiol},
	volume = {113},
	number = {5},
	year = {2015},
	month = {2015 Mar 1},
	pages = {1656-69},
	abstract = {Visual recognition takes a small fraction of a second and relies on the cascade of signals along the ventral visual stream. Given the rapid path through multiple processing steps between photoreceptors and higher visual areas, information must progress from stage to stage very quickly. This rapid progression of information suggests that fine temporal details of the neural response may be important to the brain{\textquoteright}s encoding of visual signals. We investigated how changes in the relative timing of incoming visual stimulation affect the representation of object information by recording intracranial field potentials along the human ventral visual stream while subjects recognized objects whose parts were presented with varying asynchrony. Visual responses along the ventral stream were sensitive to timing differences as small as 17 ms between parts. In particular, there was a strong dependency on the temporal order of stimulus presentation, even at short asynchronies. From these observations we infer that the neural representation of complex information in visual cortex can be modulated by rapid dynamics on scales of tens of milliseconds.},
	issn = {1522-1598},
	doi = {10.1152/jn.00556.2014},
	author = {Singer, Jedediah M and Madsen, Joseph R and Anderson, William S and Kreiman, Gabriel}
}
@article {1522708,
	title = {Recent advances in the management of non-infectious posterior uveitis},
	journal = {Int Ophthalmol},
	volume = {40},
	number = {11},
	year = {2020},
	month = {2020 Nov},
	pages = {3187-3207},
	abstract = {PURPOSE: To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU). METHODS: We performed a thorough review of current literature using PubMed, Google Scholar and Clinicaltrials.gov to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials. RESULTS: The current management regimen for non-infectious posterior uveitis includes corticosteroids, immunomodulatory therapies and anti-metabolites. However, NIPU requires long-term management for efficacious remission of the disease and to prevent disease relapse. Long-term safety issues associated with steroids have led to efforts to develop novel therapeutic agents including biological response modulators and immunosuppressants. The current therapeutic agents in various stages of development include calcineurin inhibitors, biologic response modifiers and a more a comprehensive modalities like ocular gene therapy as well as novel drug delivery mechanisms for higher bioavailability to the target tissues, with minimal systemic effects. CONCLUSION: Novel efficacious therapeutic modalities under development will help overcome the challenges associated with the traditional therapeutic agents.},
	issn = {1573-2630},
	doi = {10.1007/s10792-020-01496-0},
	author = {Singh, Rohan Bir and Sinha, Shruti and Saini, Chhavi and Elbasiony, Elsayed and Thakur, Sahil and Agarwal, Aniruddha}
}
@article {541251,
	title = {Recombination of the epsilon determinant and corneal tropism: Human adenovirus species D types 15, 29, 56, and 69.},
	journal = {Virology},
	volume = {485},
	year = {2015},
	month = {2015 Nov},
	pages = {452-9},
	abstract = {Viruses within human adenovirus species D (HAdV-D) infect epithelia at essentially every mucosal site. Hypervariable loops 1 and 2 of the hexon capsid protein contain epitopes that together form the epsilon determinant for serum neutralization. We report our analyses comparing HAdV-D15, 29, 56, and the recently identified type 69, each with highly similar hexons and the same serum neutralization profile, but otherwise disparate genomes. Of these, only HAdV-D type 56 is associated with epidemic keratoconjunctivitis (EKC), a severe infection of ocular surface epithelium and underlying corneal stroma. In the mouse adenovirus keratitis model, all four viruses induced inflammation. However, HAdV-D56 entry into human corneal epithelial cells and fibroblasts in vitro dramatically exceeded that of the other three viruses. We conclude that the hexon epsilon determinant is not a prime contributor to corneal tropism.},
	issn = {1096-0341},
	doi = {10.1016/j.virol.2015.08.018},
	author = {Singh, Gurdeep and Zhou, Xiaohong and Lee, Jeong Yoon and Yousuf, Mohammad A and Ramke, Mirja and Ismail, Ashrafali M and Lee, Ji Sun and Robinson, Christopher M and Seto, Donald and Dyer, David W and Jones, Morris S and Rajaiya, Jaya and Chodosh, James}
}
@article {1709646,
	title = {Retinal vascular occlusion following SARS-CoV-2 vaccination: A VAERS database analysis},
	journal = {Ophthalmol Sci},
	year = {2023},
	month = {2023 Jun 20},
	pages = {100354},
	abstract = {PURPOSE: To evaluate the cases of retinal vessel occlusion following COVID-19 vaccination and evaluate the onset interval and clinical presentations in patients diagnosed with vaccine associated retinal artery occlusion (RAO) and retinal vein occlusion (RVO). DESIGN: Retrospective study of the cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) between December 11, 2020 and July 1, 2022. PARTICIPANTS: Patients diagnosed with retinal vessel occlusion following vaccination with BNT162b2, mRNA-1273, and Ad26.COV2.S globally. METHODS: We performed a descriptive analysis of the patient demographics and clinical presentation in patients with retinal vessel occlusion. The correlation between the vaccines and continuous and categorical variables were assessed. We performed the post-hoc analysis to evaluated the association between RAO and RVO onset post-vaccination, and vaccine and dosage. Finally, a 30-day reverse analysis for RAO and RVO onset following administration of vaccine. A major limitation in the methods of this study is the lack of control group for assessing the risk of retinal vessel occlusive disease in patients who received the vaccine compared to the patients who were unvaccinated. MAIN OUTCOME MEASURES: The crude reporting rate of retinal vessel occlusion following SARS-CoV-2 vaccine. The ocular and systemic presentations, onset duration and short term risk of RAO and RVO following vaccination. RESULTS: During the study period, 1351 retinal vessel occlusion cases were reported globally. The crude reporting rates of retinal vessel occlusion for BNT162b2, mRNA-1273, and Ad26.COV2.S were 0.36, 0.41, and 0.69, respectively. The majority of the retinal vessel occlusion cases were reported following BNT162b2 (n=606, 74.17\%). The mean age of patients with RVO and RAO was 58.54 {\textpm} 16.06 years and 64.63 {\textpm} 16.16 years, respectively. In the cohort, 817 and 433 patients were diagnosed with RVO and RAO, respectively. Most cases of RVO (41.12\%) and RAO (48.27\%) were reported within the first week post-vaccination. We observed that the mean onset interval for RVO was significantly longer in patients who received Ad26.Cov2.S (54.07 {\textpm} 88.98 days) compared to BNT162b2 (18.07 {\textpm} 28.66 days) and mRNA-1273 (22.85 {\textpm} 38.13 days) vaccines (p\&lt;0.0001). This was further confirmed by post-hoc analysis, which revealed a significantly longer onset duration for the Ad26.Cov2.S compared to BNT162b2 and mRNA 1273 vaccines (p\&lt;0.0001). The reverse Kaplan Meier 30-day risk analysis showed a significant a higher risk of RVO onset following BNT162b2 compared to other vaccines(p\&lt;0.0001). CONCLUSIONS: The low crude reporting rate highlights a low safety concern for retinal vessel occlusion following SARS-CoV-2 vaccination. This study provides insights into possible temporal association between reported retinal vessel occlusion events with SARS-CoV-2 vaccines, however further insights are needed to understand the underlying immunopathological mechanisms that promote thrombosis of retinal vasculature on vaccine administration.},
	issn = {2666-9145},
	doi = {10.1016/j.xops.2023.100354},
	author = {Singh, Rohan Bir and Parmar, Uday Pratap Singh and Gupta, Rudraksh and Vega Garcia, Antonio Jacobo and Cho, Wonkyung and Singh, Kanwar Partap and Agarwal, Aniruddha}
}
@article {1424818,
	title = {Divergent Evolution of E1A CR3 in Human Adenovirus Species D},
	journal = {Viruses},
	volume = {11},
	number = {2},
	year = {2019},
	month = {2019 Feb 08},
	abstract = {Adenovirus E1A is the first viral protein expressed during infection. E1A controls critical aspects of downstream viral gene expression and cell cycle deregulation, and its function is thought to be highly conserved among adenoviruses. Various bioinformatics analyses of E1A from 38 human adenoviruses of species D (HAdV-D), including likelihood clade model partitioning, provided highly significant evidence of divergence of HAdV-Ds into two distinct groups for the conserved region 3 (CR3), present only in the E1A 13S isoform. This variance within E1A 13S of HAdV-Ds was not found in any other human adenovirus (HAdV) species. By protein sequence and structural analysis, the zinc finger motif of E1A CR3, previously shown as critical for transcriptional activation, showed the greatest differences. Subsequent codon usage bias analysis revealed substantial divergence in E1A 13S between the two groups of HAdV-Ds, suggesting that these two sub-groups of HAdV-D evolved under different cellular conditions. Hence, HAdV-D E1A embodies a previously unappreciated evolutionary divergence among HAdVs.},
	issn = {1999-4915},
	doi = {10.3390/v11020143},
	author = {Singh, Gurdeep and Ismail, Ashrafali M and Lee, Jeong Yoon and Ramke, Mirja and Lee, Ji Sun and Dyer, David W and Seto, Donald and Rajaiya, Jaya and Chodosh, James}
}
@article {1661593,
	title = {Vaccine-associated corneal graft rejection following SARS-CoV-2 vaccination: a CDC-VAERS database analysis},
	journal = {Br J Ophthalmol},
	volume = {108},
	number = {1},
	year = {2023},
	month = {2023 Dec 18},
	pages = {17-22},
	abstract = {PURPOSE: To evaluate the cases of corneal graft rejection following SARS-CoV-2 vaccination reported to Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. METHODS: A descriptive analysis of the demographics, clinical history and presentation was performed. We evaluated the correlation between the vaccines and duration of vaccine-associated graft rejection (VAR) onset following vaccination using a one-way analysis of variance test. A post hoc analysis was performed between VAR onset-interval following vaccination dose and vaccine type. Finally, a 30-day cumulative incidence analysis was performed to assess the risk of VAR in short term following different doses, vaccines and type of corneal transplantation. RESULTS: A total of 55 eyes of 46 patients were diagnosed with VAR following vaccination with BNT162b2 (73.91\%) and mRNA-1273 (26.09\%). The mean age of the patients was 62.76{\textpm}15.83 years, and 28 (60.87\%) were female. The patients diagnosed with VAR had undergone penetrating keratoplasty (61.82\%), Descemet membrane endothelial keratoplasty (12.73\%), descemet stripping endothelial keratoplasty (18.18\%), anterior lamellar keratoplasty (3.64\%) and corneal limbal allograft transplantation (1.82\%). The mean time for VAR since penetrating and endothelial keratoplasty was 8.42{\textpm}9.23 years and 4.18{\textpm}4.40 years, respectively. 45.65\% of the cases of VAR were reported after the second dose of vaccine. The duration of VAR onset was significantly shorter after the second dose compared with the first and booster doses (p=0.0165) and in patients who underwent endothelial keratoplasty compared with penetrating keratoplasty (p=0.041). CONCLUSIONS: This study outlines a possible temporal relationship between corneal graft rejection and SARS-CoV-2 vaccination. An earlier onset of VAR was observed in patients who had a history of endothelial keratoplasty and following the second dose of vaccination.},
	keywords = {Adverse Drug Reaction Reporting Systems, Aged, BNT162 Vaccine, Corneal Diseases, Corneal Transplantation, COVID-19, COVID-19 Vaccines, Descemet Stripping Endothelial Keratoplasty, Female, Graft Rejection, Graft Survival, Humans, Keratoplasty, Penetrating, Male, Middle Aged, Postoperative Complications, Retrospective Studies, Vaccination},
	issn = {1468-2079},
	doi = {10.1136/bjo-2022-322512},
	author = {Singh, Rohan Bir and Li, Jeffrey and Parmar, Uday Pratap Singh and Jeng, Bennie H and Jhanji, Vishal}
}
@article {1364548,
	title = {Overreliance on the hexon gene, leading to misclassification of human adenoviruses},
	journal = {J Virol},
	volume = {86},
	number = {8},
	year = {2012},
	month = {2012 Apr},
	pages = {4693-5},
	abstract = {The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences with identical hexon genes, which were the same as the one previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss coinfections. Whole-genome sequencing remains the gold standard for proper classification of HAdVs.},
	keywords = {Adenoviruses, Human, Capsid Proteins, Cell Line, Computational Biology, Genome, Viral, Humans, Molecular Sequence Data, Phylogeny, Sequence Analysis, DNA},
	issn = {1098-5514},
	doi = {10.1128/JVI.06969-11},
	author = {Singh, Gurdeep and Robinson, Christopher M and Dehghan, Shoaleh and Schmidt, Timothy and Seto, Donald and Jones, Morris S and Dyer, David W and Chodosh, James}
}
@article {1559529,
	title = {First Line of Defense in COVID-19: Masks in Clinical Practice},
	journal = {Asia Pac J Public Health},
	year = {2020},
	month = {2020 Dec 08},
	pages = {1010539520979928},
	abstract = {The current evidence suggests that masks are efficacious in limiting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Although cloth masks are effective in outdoor environments, there is a consensus about the requirement of N95 masks or respirators when working in close proximity to patients who may be asymptomatic carriers, specifically in ophthalmology clinics, where slit-lamp examinations, noncontact tonometry, and other procedures place the physicians and patients in close proximity with each other. In this report, we review the available evidence regarding the efficacy of different types of masks in clinical practice in ophthalmology.},
	issn = {1941-2479},
	doi = {10.1177/1010539520979928},
	author = {Singh, Tanu and Ichhpujani, Parul and Singh, Rohan Bir}
}
@article {1651064,
	title = {Imaging-based Assessment of Choriocapillaris: A Comprehensive Review},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {5},
	year = {2023},
	month = {2023 Jul},
	pages = {405-426},
	abstract = {PURPOSE: Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium. METHODS: A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid. RESULTS: The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed. CONCLUSION: The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.},
	keywords = {Central Serous Chorioretinopathy, Choroid, Choroiditis, Diabetic Retinopathy, Fluorescein Angiography, Humans, Macular Degeneration, Tomography, Optical Coherence},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2109939},
	author = {Singh, Rohan Bir and Perepelkina, Tatiana and Testi, Ilaria and Young, Benjamin K and Mirza, Tuba and Invernizzi, Alessandro and Biswas, Jyotirmay and Agarwal, Aniruddha}
}
@article {1460366,
	title = {Down and out: acquired oculomotor nerve palsy},
	journal = {BMJ Case Rep},
	volume = {12},
	number = {8},
	year = {2019},
	month = {2019 Aug 21},
	issn = {1757-790X},
	doi = {10.1136/bcr-2019-231485},
	author = {Singh, Rohan Bir and Shergill, Sukhman and Singh, Kanwar Partap and Thakur, Sahil}
}
@article {1573128,
	title = {Pigment Epithelium-Derived Factor Enhances the Suppressive Phenotype of Regulatory T Cells in a Murine Model of Dry Eye Disease},
	journal = {Am J Pathol},
	volume = {191},
	number = {4},
	year = {2021},
	month = {2021 04},
	pages = {720-729},
	abstract = {Pigment epithelium-derived factor (PEDF) is a widely expressed 50-kDa glycoprotein belonging to the serine protease inhibitor family, with well-established anti-inflammatory functions. Recently, we demonstrated the immunoregulatory role played by PEDF in dry eye disease (DED) by suppressing the maturation of antigen-presenting cells at the ocular surface following exposure to the desiccating stress. In this study, we evaluated the effect of PEDF on the immunosuppressive characteristics of regulatory T cells (Tregs), which are functionally impaired in DED. In the presence of PEDF, the in\&nbsp;vitro cultures prevented proinflammatory cytokine (associated with type 17 helper T cells)-induced loss of frequency and suppressive phenotype of Tregs derived from normal mice. Similarly, PEDF maintained the in\&nbsp;vitro frequency and enhanced the suppressive phenotype of Tregs derived from DED mice. On systemically treating DED mice with PEDF, moderately higher frequencies and significantly enhanced suppressive function of Tregs were observed in the draining lymphoid tissues, leading to the efficacious amelioration of the disease. Our results demonstrate that PEDF promotes the suppressive capability of Tregs and attenuates their type 17 helper T-cell-mediated dysfunction in DED, thereby playing a role in the suppression of DED.},
	keywords = {Animals, Anti-Inflammatory Agents, Antigen-Presenting Cells, Cytokines, Disease Models, Animal, Dry Eye Syndromes, Eye Proteins, Female, Mice, Inbred C57BL, Nerve Growth Factors, Phenotype, Serpins, T-Lymphocytes, Regulatory, Th17 Cells},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.01.003},
	author = {Singh, Rohan B and Blanco, Tomas and Mittal, Sharad K and Alemi, Hamid and Chauhan, Sunil K and Chen, Yihe and Dana, Reza}
}
@article {1511488,
	title = {Pigment Epithelium-derived Factor secreted by corneal epithelial cells regulates dendritic cell maturation in dry eye disease},
	journal = {Ocul Surf},
	volume = {18},
	number = {3},
	year = {2020},
	month = {2020 07},
	pages = {460-469},
	abstract = {PURPOSE: In this study, we quantify Pigment Epithelium-derived Factor (PEDF) secreted by corneal epithelial cells and evaluate its immunomodulatory functions in a murine model of dry eye disease (DED). METHODS: We induced DED in female C57BL/6 mice using a controlled environment chamber for 14 days. We quantified mRNA expression of Serpinf1 gene and PEDF protein synthesis by corneal epithelial cells (CEpCs) using RT-PCR and ELISA. CEpCs from normal or DED mice were cultured with IFNγ-stimulated-dendritic cells (DCs) for 24\&nbsp;h, and expression of MHC-II and CD86 by DCs was determined using flow cytometry. Next, we either added recombinant PEDF (rPEDF) or anti-PEDF antibody to co-culture, and DC expression of the above maturation markers was quantified. Lastly, we treated DED mice with either topical rPEDF, anti-PEDF Ab or murine serum albumin (MSA), and DC maturation, expression of pro-inflammatory cytokines, and DED severity were investigated. RESULTS: Serpinf1 mRNA expression and PEDF protein production levels by CEpCs were upregulated in DED. CEpCs from DED mice exhibited an enhanced suppressive effect on the expression of MHC-II and CD86 by DCs, compared to normal mice. This effect was abolished by blocking endogenous PEDF with anti-PEDF Ab or enhanced by supplementing with rPEDF. Treatment with anti-PEDF antibody blocked the effect of endogenous-PEDF and increased DC maturation, expression of pro-inflammatory cytokines in conjunctivae, and exacerbated disease severity in DED mice. Conversely, topical rPEDF enhanced the suppressive effect of endogenous PEDF on DC maturation, decreased expression of pro-inflammatory cytokines in conjunctivae, and reduced disease severity. CONCLUSIONS: The results from our study elucidate the role of PEDF in impeding DC maturation, and suppression of ocular surface inflammation, explicating a promising therapeutic potential of PEDF in limiting the corneal epitheliopathy as a consequence of DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.05.002},
	author = {Singh, Rohan Bir and Blanco, Tomas and Mittal, Sharad K and Taketani, Yukako and Chauhan, Sunil K and Chen, Yihe and Dana, Reza}
}
@article {1598032,
	title = {Ocular Manifestations of Neuronal Ceroid Lipofuscinoses},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {7},
	year = {2021},
	month = {2021 Oct 03},
	pages = {582-595},
	abstract = {Neuronal ceroid lipofuscinoses (NCLs) are a group of rare neurodegenerative storage disorders associated with devastating visual prognosis, with an incidence of 1/1,000,000 in the United States and comparatively higher incidence in European countries. The pathophysiological mechanisms causing NCLs occur due to enzymatic or transmembrane defects in various sub-cellular organelles including lysosomes, endoplasmic reticulum, and cytoplasmic vesicles. NCLs are categorized into different types depending upon the underlying cause i.e., soluble lysosomal enzyme deficiencies or non-enzymatic deficiencies (functions of identified proteins), which are sub-divided based on an axial classification system. In this review, we have\&nbsp;evaluated the current evidence in the literature and reported the incidence rates, underlying mechanisms and currently available management protocols for these rare set of neuroophthalmological disorders. Additionally, we also highlighted the potential therapies under development that can expand the treatment of these rare disorders beyond symptomatic relief.},
	keywords = {Eye, Humans, Lysosomes, Neuronal Ceroid-Lipofuscinoses},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1936571},
	author = {Singh, Rohan Bir and Gupta, Prakash and Kartik, Akash and Farooqui, Naba and Singhal, Sachi and Shergill, Sukhman and Singh, Kanwar Partap and Agarwal, Aniruddha}
}
@article {1318876,
	title = {Advances in medical polymer technology towards the panacea of complex 3D tissue and organ manufacture},
	journal = {Am J Surg},
	volume = {217},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {807-808},
	issn = {1879-1883},
	doi = {10.1016/j.amjsurg.2018.05.012},
	author = {Singh, Deepti and Thomas, Daniel}
}
@article {1307449,
	title = {Ethics of a therapeutic trial: addressing limitations of an active intervention in optic nerve lymphoma},
	journal = {BMJ Case Rep},
	volume = {2018},
	year = {2018},
	month = {2018 Mar 28},
	abstract = {We report a unique case of optic nerve lymphoma after completion of chemotherapy for non-Hodgkin{\textquoteright}s lymphoma. The uncommon nature of presentation, our therapeutic dilemma and the further course of treatment are reported. In cases with extremely poor prognosis, unnecessary treatment puts additional strain both financially and psychologically on the patients and their family. Therapeutic focus should be on hospice care and family counselling. The decision to not treat is a crucial component of cancer management; however, the ethics of this decision are yet to be suitably addressed by the literature.},
	issn = {1757-790X},
	doi = {10.1136/bcr-2018-224217},
	author = {Singh, Rohan Bir and Thakur, Sahil and Ichhpujani, Parul and Kumar, Suresh}
}
@article {1580463,
	title = {Ocular complications of perioperative anesthesia: a review},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {259},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {2069-2083},
	abstract = {Ocular complications associated with anesthesia in ocular and non-ocular surgeries are rare adverse events which may present with clinical presentations vacillating between easily treatable corneal abrasions to more serious complication such as irreversible bilateral vision loss. In this review, we outline the different techniques of anesthetic delivery in ocular surgeries and highlight the incidence and etiologies of associated injuries. The changes in vision in non-ocular surgeries are mistaken for residual sedation or anesthetics, therefore require high clinical suspicion on part of the treating ophthalmologists, to ensure early diagnosis, adequate and swift management especially in surgeries such as cardiac, spine, head and neck, and some orthopedic procedures, that have a comparatively higher incidence of ocular complications. In this article, we review the literature for reports on the clinical incidence of different ocular complications associated with anesthesia in non-ocular surgeries and outline the current understanding of pathophysiological processes associated with these adverse events.},
	keywords = {Anesthesia, Corneal Injuries, Eye, Humans, Ophthalmologic Surgical Procedures, Vision Disorders},
	issn = {1435-702X},
	doi = {10.1007/s00417-021-05119-x},
	author = {Singh, Rohan Bir and Khera, Tanvi and Ly, Victoria and Saini, Chhavi and Cho, Wonkyung and Shergill, Sukhman and Singh, Kanwar Partap and Agarwal, Aniruddha}
}
@article {1319481,
	title = {Why Does the Cortex Reorganize after Sensory Loss?},
	journal = {Trends Cogn Sci},
	volume = {22},
	number = {7},
	year = {2018},
	month = {2018 Jul},
	pages = {569-582},
	abstract = {A growing body of evidence demonstrates that the brain can reorganize dramatically following sensory loss. Although the existence of such neuroplastic crossmodal changes is not in doubt, the functional significance of these changes remains unclear. The dominant belief is that reorganization is compensatory. However, results thus far do not unequivocally indicate that sensory deprivation results in markedly enhanced abilities in other senses. Here, we consider alternative reasons besides sensory compensation that might drive the brain to reorganize after sensory loss. One such possibility is that the cortex reorganizes not to confer functional benefits, but to avoid undesirable physiological consequences of sensory deafferentation. Empirical assessment of the validity of this and other possibilities defines a rich program for future research.},
	issn = {1879-307X},
	doi = {10.1016/j.tics.2018.04.004},
	author = {Singh, Amy Kalia and Phillips, Flip and Merabet, Lotfi B and Sinha, Pawan}
}
@article {1664964,
	title = {Herpetic Eye Disease After SARS-CoV-2 Vaccination: A CDC-VAERS Database Analysis},
	journal = {Cornea},
	volume = {42},
	number = {6},
	year = {2023},
	month = {2023 Jun 01},
	pages = {731-738},
	abstract = {PURPOSE: The aim of this study was to evaluate the cases of herpes simplex and zoster ophthalmicus after SARS-CoV-2 vaccination and assess the clinical presentations in patients. METHODS: A retrospective analysis of cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) between December 11, 2020, and July 1, 2022. Patients diagnosed with herpes simplex ophthalmicus (HSO) and herpes zoster ophthalmicus (HZO) after vaccination with BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) were included in the study. We performed a descriptive analysis of patient demographics, history, and ophthalmic and systemic clinical presentations. The correlations between vaccine type and continuous variables were assessed by the one-way analysis of variance test. In addition, we used the Pearson χ 2 test to assess the association between 3 vaccines and categorical variables. A post hoc analysis was performed between HSO and HZO onset intervals after vaccination, dose, and vaccine type. The 30-day risk analysis was also performed for HSO and HZO onset postvaccination using the reverse Kaplan-Meier analysis. RESULTS: A total of 1180 cases of HZO (983, 83.30\%) and HSO (180, 15.25\%) were reported. The mean age of patients with HZO and HSO was 59.02 {\textpm} 19.05 and 52.68 {\textpm} 17.83 years, respectively. Most of the cases of HZO (795, 80.87\%) and HSO (131, 72.78\%) were reported in patients who received BNT162b2. In the cohort, 63.28\% and 65.56\% diagnosed with HZO and HSO were women. About one third of HZO (36.52\%) and HSO (35.56\%) cases were reported after the first dose. More than half of the cases of HZO (61.34\%) and HSO (64.45\%) were reported within the first 2 weeks after vaccination. The estimated crude reporting rate (per million doses) in the United States was 0.25, 0.22, and 0.47 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The onset interval for HZO was significantly shorter in patients who received BNT162b2 (20.51 {\textpm} 56.20 days, P = 0.030) compared with patients who received mRNA-1273 (36.56 {\textpm} 108.67 days) and Ad26.COV2.S (39.66 {\textpm} 60.15 days) vaccines. The 30-day risk analysis showed a significantly higher risk of HZO after BNT162b2 than the other 2 vaccines ( P = 0.011). CONCLUSIONS: The low crude reporting rate suggests that HZO and HSO after SARS-CoV-2 vaccination occur rarely. This study provides insights into the possible temporal association between reported HSO and HZO after SARS-CoV-2 vaccines; however, further investigations are required to delineate the possible underlying immunological mechanisms.},
	keywords = {2019-nCoV Vaccine mRNA-1273, Ad26COVS1, Adult, Adverse Drug Reaction Reporting Systems, Aged, BNT162 Vaccine, Centers for Disease Control and Prevention, U.S., COVID-19, COVID-19 Vaccines, Female, Herpes Simplex, Herpes Zoster Ophthalmicus, Humans, Keratitis, Herpetic, Male, Middle Aged, Retrospective Studies, SARS-CoV-2, United States, Vaccination, Vaccines},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003246},
	author = {Singh, Rohan Bir and Parmar, Uday Pratap Singh and Ichhpujani, Parul and Jeng, Bennie H and Jhanji, Vishal}
}
@article {1559575,
	title = {Uveal Melanoma in BAP1 Tumor Predisposition Syndrome: Estimation of Risk},
	journal = {Am J Ophthalmol},
	volume = {224},
	year = {2021},
	month = {2021 Apr},
	pages = {172-177},
	abstract = {PURPOSE: To estimate point prevalence of uveal melanoma in the patients with germline BAP1 pathogenic variant. DESIGN: Cohort study with risk assessment using Bayesian analysis. METHODS: The point prevalence estimate was obtained by Bayes{\textquoteright}s rule of reverse conditional probabilities. The probability of uveal melanoma given that BAP1 mutation exists was derived from the prevalence of uveal melanoma, prevalence of germline BAP1 pathogenic variants, and the probability of germline BAP1 pathogenic variant given that uveal melanoma is present. Confidence intervals (CIs) for each variable were calculated as the mean of Bernoulli random variables and for the risk estimate, by the delta method. The age at diagnosis and the gender of the uveal melanoma patients with BAP1 germline pathogenic variants obtained from previous publications or from authors{\textquoteright} unpublished cohort was compared with those in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The point prevalence of uveal melanoma in patients with the germline BAP1 pathogenic variants in the US population was estimated to be 2.8\% (95\% CI, 0.88\%-4.81\%). In the SEER database, the median age at diagnosis of uveal melanomas was 63 (range 3-99 years) with a male-to-female ratio of 1.01:1. In comparison, uveal melanoma cases with BAP1 germline pathogenic variants from the US population (n\&nbsp;= 27) had a median age at diagnosis of 50.5 years (range 16-71). CONCLUSIONS: Quantification of the risk of developing uveal melanoma can enhance counseling regarding surveillance in patients with germline BAP1 pathogenic variant.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.12.005},
	author = {Singh, Nakul and Singh, Rahul and Bowen, Randy Chris and Abdel-Rahman, Mohamed H and Singh, Arun D}
}
@article {1782306,
	title = {Prevalence and Economic Burden of Keratoconus in the United States},
	journal = {Am J Ophthalmol},
	volume = {259},
	year = {2024},
	month = {2024 Mar},
	pages = {71-78},
	abstract = {PURPOSE: To assess the prevalence and economic burden of keratoconus in the United States. DESIGN: Retrospective cohort study. METHODS: Patients enrolled in Medicaid and Children{\textquoteright}s Health Insurance Program (CHIP) who were diagnosed with keratoconus between 2016 and 2019 were included. The data reported to the Centers for Disease Control and Prevention (CDC) Vision and Eye Health Surveillance System (VEHSS) were analyzed. The crude prevalence rates (national and statewise) were obtained from the database and extrapolated to estimate the keratoconus case count in the United States. The keratoconus prevalence was compared between male and female individuals using the Mann-Whitney test, whereas Brown-Forsythe 1-way analysis of variance was used to compare prevalence between age and racial groups. The Dunnett T3 multiple comparison test was used for intergroup comparison. Finally, the economic burden of keratoconus was assessed by inflation-adjusted direct costs to patients and total cases in the country. RESULTS: In the cohort of 69,502,000 patients enrolled for Medicaid and CHIP, the national prevalence of keratoconus was computed to be 0.04\% in 2019 and had increased from 0.03\% in 2016. The highest prevalence of keratoconus was observed in patients 18 to 39 years of age, followed by patients 40 to 64 years of age; comparable prevalence rates were observed in these age groups in the Black population. The prevalence was moderately higher in female compared to male individuals; however, significantly higher keratoconus prevalence was observed in Black female individuals compared to male individuals. A significantly high prevalence of keratoconus was observed in the Black population, followed by Hispanic population. In 2019, the average inflation-adjusted lifetime cost of keratoconus treatment was USD 28,766.69, with a cumulative economic burden of USD 3.8 billion. CONCLUSIONS: In the United States, keratoconus is most prevalent in individuals 18 to 39 years of age. The keratoconus prevalence is higher in the Black population, specifically female individuals, and the diagnosis is often delayed in these patients.},
	keywords = {Adult, Child, Cost of Illness, Female, Financial Stress, Health Care Costs, Humans, Keratoconus, Male, Middle Aged, Prevalence, Retrospective Studies, United States},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.11.009},
	author = {Singh, Rohan Bir and Parmar, Uday Pratap Singh and Jhanji, Vishal}
}
@article {1647875,
	title = {Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease},
	journal = {Ocul Surf},
	year = {2022},
	month = {2022 Jul 14},
	abstract = {PURPOSE: To determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD). DESIGN: Retrospective cohort study. METHODS: We performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients. MAIN OUTCOME MEASURE: Prevalence of NK in chronic oGVHD. RESULTS: We identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14\%. The mean age of oGVHD patients with NK was 62.6 {\textpm} 12.9 years; 48\% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56\%, 20\%, and 24\% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 {\textpm} 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients. CONCLUSIONS: The prevalence of NK in chronic oGVHD patients was 14\% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2022.07.001},
	author = {Singh, Rohan Bir and Yuksel, Erdem and Sinha, Shruti and Wang, Shudan and Taketani, Yukako and Luznik, Zala and Yin, Jia and Dohlman, Thomas H and Dana, Reza}
}
@article {1664945,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {130},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {e18-e19},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.11.024},
	author = {Singh, Rohan Bir and Parmar, Uday Pratap Singh and Kahale, Francesca and Agarwal, Aniruddha and Tsui, Edmund}
}
@article {1623352,
	title = {Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis},
	journal = {Prog Retin Eye Res},
	volume = {88},
	year = {2022},
	month = {2022 May},
	pages = {101028},
	abstract = {Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the "anti-biotic era". Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins. In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.},
	keywords = {Bacteria, Cornea, Eye Infections, Bacterial, Humans, Keratitis},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2021.101028},
	author = {Singh, Rohan Bir and Das, Sujata and Chodosh, James and Sharma, Namrata and Zegans, Michael E and Kowalski, Regis P and Jhanji, Vishal}
}
@article {1363204,
	title = {Homologous recombination in E3 genes of human adenovirus species D},
	journal = {J Virol},
	volume = {87},
	number = {22},
	year = {2013},
	month = {2013 Nov},
	pages = {12481-8},
	abstract = {Genes within the E3 transcription unit of human adenoviruses modulate host immune responses to infection. A comprehensive genomics and bioinformatics analysis of the E3 transcription unit for 38 viruses within human adenovirus species D (HAdV-D) revealed distinct and surprising patterns of homologous recombination. Homologous recombination was identified in open reading frames for E3 CR1α, CR1β, and CR1γ, similar to that previously observed with genes encoding the three major structural capsid proteins, the penton base, hexon, and fiber.},
	keywords = {Adenovirus E3 Proteins, Adenovirus Infections, Human, Adenoviruses, Human, Capsid Proteins, Computational Biology, DNA, Viral, Evolution, Molecular, Genome, Viral, Homologous Recombination, Humans, Phylogeny},
	issn = {1098-5514},
	doi = {10.1128/JVI.01927-13},
	author = {Singh, Gurdeep and Robinson, Christopher M and Dehghan, Shoaleh and Jones, Morris S and Dyer, David W and Seto, Donald and Chodosh, James}
}
@article {1773606,
	title = {Prevalence and Economic Burden of Fuchs Endothelial Corneal Dystrophy in the Medicare Population in the United States},
	journal = {Cornea},
	year = {2023},
	month = {2023 Oct 31},
	abstract = {PURPOSE: The aim of this study was to assess the prevalence and economic burden of Fuchs endothelial corneal dystrophy (FECD) in patients older than 65 years in the United States. METHODS: A retrospective analysis of the Medicare data reported to the Vision and Eye Health Surveillance System including patients diagnosed with FECD between 2014 and 2019 was performed. The crude prevalence rate of FECD was assessed and extrapolated to estimate the total case burden in the United States. The prevalence data were further compared between men and women and different racial groups. In addition, the economic burden was computed using inflation-adjusted direct costs of treatment to patients. RESULTS: The Medicare database included 25,432,700 patients older than 65 years. The national prevalence of FECD in this population cohort was calculated to be 1.12\% in 2019. In 2019, FECD case burden in Medicare patients older than 65 years was 284,846 and total estimated FECD case count in the country in this age group was 591,226. FECD prevalence was significantly higher in women as compared to men during the 6-year period evaluated in this study. The intergroup comparison revealed that FECD prevalence in the White population was significantly higher than all other racial groups (P \&lt; 0.0001). The total inflation-adjusted economic burden of FECD in the United States in 2019 was USD 291.648 million and has increased from USD 243.998 million over the 6-year study period. CONCLUSIONS: The estimated prevalence of FECD in the individuals older than 65 years is 1.12\% in the United States. FECD prevalence is significantly higher in women and White population compared with other ethnicities.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003416},
	author = {Singh, Rohan Bir and Parmar, Uday Pratap Singh and Kahale, Francesca and Jeng, Bennie H and Jhanji, Vishal}
}
@article {1806636,
	title = {Machine Learning-Derived Baseline Visual Field Patterns Predict Future Glaucoma Onset in the Ocular Hypertension Treatment Study},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {65},
	number = {2},
	year = {2024},
	month = {2024 Feb 01},
	pages = {35},
	abstract = {PURPOSE: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). METHODS: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. RESULTS: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95\% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95\% CI, 1.09-1.37), AT15 (HR = 1.26; 95\% CI, 1.12-1.41), and AT17 (HR = 1.17; 95\% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (\&gt;95th percentile or \&lt;75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. CONCLUSIONS: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting.},
	keywords = {Glaucoma, Open-Angle, Humans, Intraocular Pressure, machine learning, Ocular Hypertension, Optic Disk, Vision Disorders, Visual Field Tests, Visual Fields},
	issn = {1552-5783},
	doi = {10.1167/iovs.65.2.35},
	author = {Singh, Rishabh K and Smith, Sophie and Fingert, John and Gordon, Mae and Kass, Michael and Scheetz, Todd and Segr{\`e}, Ayellet V and Wiggs, Janey and Tobias Elze and Zebardast, Nazlee}
}
@article {1498250,
	title = {Promising therapeutic drug delivery systems for glaucoma: a comprehensive review},
	journal = {Ther Adv Ophthalmol},
	volume = {12},
	year = {2020},
	month = {2020 Jan-Dec},
	pages = {2515841420905740},
	abstract = {The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include-inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27\% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment.},
	issn = {2515-8414},
	doi = {10.1177/2515841420905740},
	author = {Singh, Rohan B and Ichhpujani, Parul and Thakur, Sahil and Jindal, Sumeet}
}
@article {1593836,
	title = {Ocular redness - I: Etiology, pathogenesis, and assessment of conjunctival hyperemia},
	journal = {Ocul Surf},
	volume = {21},
	year = {2021},
	month = {2021 Jul},
	pages = {134-144},
	abstract = {The translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation of the conjunctival microvasculature consisting of extensive branching of superficial and deep arterial systems and corresponding drainage pathways, and the translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation. Conjunctival hyperemia is caused by a pathological vasodilatory response of the microvasculature in response to inflammation due to a myriad of infectious and non-infectious etiologies. It is one of the most common contributors of ocular complaints that prompts visits to medical centers. Our understanding of these neurogenic and immune-mediated pathways has progressed over time and has played a critical role in developing targeted novel therapies. Due to a multitude of underlying etiologies, patients must be accurately diagnosed for efficacious management of conjunctival hyperemia. The diagnostic techniques used for the grading of conjunctival hyperemia have also evolved from descriptive and subjective grading scales to more reliable computer-based objective grading scales.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.05.003},
	author = {Singh, Rohan Bir and Liu, Lingjia and Anchouche, Sonia and Yung, Ann and Mittal, Sharad K and Blanco, Tomas and Dohlman, Thomas H and Yin, Jia and Dana, Reza}
}
@article {1667694,
	title = {Ocular complications of plasma cell dyscrasias},
	journal = {Eur J Ophthalmol},
	volume = {33},
	number = {5},
	year = {2023},
	month = {2023 Sep},
	pages = {1786-1800},
	abstract = {Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenstr{\"o}m{\textquoteright}s macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.},
	keywords = {Eye, Eye Diseases, Humans, Paraproteinemias, Treatment Outcome},
	issn = {1724-6016},
	doi = {10.1177/11206721231155974},
	author = {Singh, Rohan Bir and Singhal, Sachi and Sinha, Shruti and Cho, Junsang and Nguyen, Anne Xuan-Lan and Dhingra, Lovedeep Singh and Kaur, Snimarjot and Sharma, Vasudha and Agarwal, Aniruddha}
}
@article {1302179,
	title = {Blueberry eye: acquired total anterior staphyloma},
	journal = {BMJ Case Rep},
	volume = {2018},
	year = {2018},
	month = {2018 Feb 24},
	issn = {1757-790X},
	doi = {10.1136/bcr-2018-224271},
	author = {Singh, Rohan Bir and Thakur, Sahil and Singh, Kanwar Partap}
}
@article {1504063,
	title = {Window to the circulatory system: Ocular manifestations of cardiovascular diseases},
	journal = {Eur J Ophthalmol},
	year = {2020},
	month = {2020 Apr 27},
	pages = {1120672120914232},
	issn = {1724-6016},
	doi = {10.1177/1120672120914232},
	author = {Singh, Rohan Bir and Saini, Chhavi and Shergill, Sukhman and Agarwal, Aniruddha}
}
@article {1773546,
	title = {Normative Percentiles of Retinal Nerve Fiber Layer Thickness and Glaucomatous Visual Field Loss},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {10},
	year = {2023},
	month = {2023 Oct 03},
	pages = {13},
	abstract = {PURPOSE: Circumpapillary retinal nerve fiber layer thickness (RNFLT) measurement aids in the clinical diagnosis of glaucoma. Spectral domain optical coherence tomography (SD-OCT) machines measure RNFLT and provide normative color-coded plots. In this retrospective study, we investigate whether normative percentiles of RNFLT (pRNFLT) from Spectralis SD-OCT improve prediction of glaucomatous visual field loss over raw RNFLT. METHODS: A longitudinal database containing OCT scans and visual fields from Massachusetts Eye \&amp; Ear glaucoma clinic patients was generated. Reliable OCT-visual field pairs were selected. Spectralis OCT normative distributions were extracted from machine printouts. Supervised machine learning models compared predictive performance between pRNFLT and raw RNFLT inputs. Regional structure-function associations were assessed with univariate regression to predict mean deviation (MD). Multivariable classification predicted MD, pattern standard deviation, MD change per year, and glaucoma hemifield test. RESULTS: There were 3016 OCT-visual field pairs that met the reliability criteria. Spectralis norms were found to be independent of age, sex, and ocular magnification. Regional analysis showed significant decrease in R2 from pRNFLT models compared to raw RNFLT models in inferotemporal sectors, across multiple regressors. In multivariable classification, there were no significant improvements in area under the curve of receiver operating characteristic curve (ROC-AUC) score with pRNFLT models compared to raw RNFLT models. CONCLUSIONS: Our results challenge the assumption that normative percentiles from OCT machines improve prediction of glaucomatous visual field loss. Raw RNFLT alone shows strong prediction, with no models presenting improvement by the manufacturer norms. This may result from insufficient patient stratification in tested norms. TRANSLATIONAL RELEVANCE: Understanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.},
	keywords = {Glaucoma, Humans, Nerve Fibers, Reproducibility of Results, Retinal Ganglion Cells, Retrospective Studies, Tomography, Optical Coherence, Vision Disorders, Visual Fields},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.10.13},
	author = {Rishabh Singh and Rauscher, Franziska G and Li, Yangjiani and Eslami, Mohammad and Kazeminasab, Saber and Zebardast, Nazlee and Wang, Mengyu and Tobias Elze}
}
@article {1528410,
	title = {Efficacy of cyanoacrylate tissue adhesive in the management of corneal thinning and perforation due to microbial keratitis},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 Aug 19},
	abstract = {PURPOSE: Report the efficacy of cyanoacrylate tissue adhesive (CTA) application in the management of corneal thinning and perforations associated with microbial keratitis. METHODS: A retrospective review of consecutive patients who underwent CTA application for corneal thinning and perforation secondary to microbiologically proven infectious keratitis between 2001 and 2018 at a single center. We defined successful CTA application as an intact globe without tectonic surgical intervention. RESULTS: The cohort included 67 patients, and 37 presented with corneal perforation while 30 had corneal thinning. The perforation/thinning was central/paracentral in 43 eyes and peripheral in 23 eyes. The underlying infectious etiologies were monomicrobial in 42 cases (35 bacterial, 3 fungal, 2 viral, and 2 acanthamoeba cases) and polymicrobial in 25 cases (22 polybacterial cases and 3 cases with a combination of Gram positive bacteria and fungus). The median duration of glue retention was 29 days. The CTA success rate was 73\%, 64\%, and 44\% at 10, 30, and 180 days, respectively. CTA application appears more successful in monomicrobial (vs. polymicrobial) and Gram positive bacterial (vs. Gram negative) keratitis but the differences are statistically non-significant. The location of perforation/thinning and the use of topical corticosteroid were not associated with CTA failure. CONCLUSION: CTA was moderately effective in restoring globe integrity in severe corneal thinning and perforation secondary to microbial keratitis in the short term. However the majority of patients require tectonic surgical intervention within 6 months. CTA application success is not significantly associated with the location of thinning/perforation or the use of topical corticosteroid.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.08.001},
	author = {Singh, Rohan Bir and Zhu, Shuyan and Yung, Ann and Dohlman, Thomas H and Dana, Reza and Yin, Jia}
}
@article {1814416,
	title = {Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study},
	journal = {JAMA Ophthalmol},
	year = {2024},
	month = {2024 Mar 14},
	abstract = {IMPORTANCE: Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification. OBJECTIVE: To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023. EXPOSURES: From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication. MAIN OUTCOMES AND MEASURES: Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models. RESULTS: Of 1009 included participants, 562 (55.7\%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P \&lt; .001). POAG risk increased 1.36\% (95\% CI, 1.08-1.64) with each higher PRS decile, with conversion ranging from 9.52\% (95\% CI, 7.09-11.95) in the lowest PRS decile to 21.81\% (95\% CI, 19.37-24.25) in the highest decile. Comparison of low-risk and high-risk PRS tertiles showed a 2.0-fold increase in 20-year POAG risk for participants of European and African ancestries. In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year (95\% CI, 0.01-1.03) decrease in age at diagnosis (P = .047). No significant linear association between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C index = 0.77) compared with the Ocular Hypertension Treatment Study baseline model (C index = 0.75) (P \&lt; .001). Each 1-SD higher PRS conferred a mean hazard ratio of 1.25 (95\% CI, 1.13-1.44) for POAG onset. CONCLUSIONS AND RELEVANCE: Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000125.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2024.0151},
	author = {Singh, Rishabh K and Zhao, Yan and Tobias Elze and Fingert, John and Gordon, Mae and Kass, Michael A and Luo, Yuyang and Pasquale, Louis R and Scheetz, Todd and Segr{\`e}, Ayellet V and Wiggs, Janey L and Zebardast, Nazlee}
}
@article {1667720,
	title = {Is ultra-thin Descemet stripping automated endothelial keratoplasty a viable alternative to Descemet membrane endothelial keratoplasty? A systematic review and meta-analysis},
	journal = {Ther Adv Ophthalmol},
	volume = {15},
	year = {2023},
	month = {2023 Jan-Dec},
	pages = {25158414221147823},
	abstract = {BACKGROUND: Ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) is a recently developed surgical procedure that has shown promising results for the management of various corneal endothelial diseases. OBJECTIVES: To evaluate the outcomes of the UT-DSAEK to the Descemet membrane endothelial keratoplasty (DMEK). DESIGN: A systematic analysis of the studies comparing UT-DSAEK with DMEK by evaluating one or more outcomes (vision, complications, and post-operative endothelial cell counts) was performed. The meta-analysis was done if two or more studies reported a common outcome. METHODS: We used PubMed, EMBASE, and SCOPUS databases to identify articles comparing the outcomes of UT-DSAEK with DMEK and performed a meta-analysis using RevMan, version 5.4. RESULTS: A total of six studies were included in this review (two randomized clinical trials and four non-randomized comparative studies). Our analysis showed the patients who underwent DMEK cases showed better visual outcomes with a mean difference of 0.06 LogMAR (95\% CI: 0.04-0.09) in BCVA, albeit with i 2 of 52\% (heterogenous values). The evidence was weak, with the most weightage on retrospective studies. UT-DSAEK showed significantly fewer complications such as graft dislocations, with an odds ratio of 0.25 (95\% CI: 0.13-0.48). There was no significant difference in the endothelial cell counts with a mean difference of 86.34 (95\%CI: -133.09 to -305.77). CONCLUSION: Although the literature is limited on UT-DSAEK with post-operative visual acuity that could be practically at par with DMEK, lesser complication rates and comparable post-operative endothelial cells could be a suitable alternative to DMEK for corneal endothelial pathologies.},
	issn = {2515-8414},
	doi = {10.1177/25158414221147823},
	author = {Singh, Tanu and Ichhpujani, Parul and Singh, Rohan Bir and Arya, Sudesh and Kumar, Suresh}
}
@article {1593859,
	title = {Ocular redness - II: Progress in development of therapeutics for the management of conjunctival hyperemia},
	journal = {Ocul Surf},
	volume = {21},
	year = {2021},
	month = {2021 Jul},
	pages = {66-77},
	abstract = {Conjunctival hyperemia is one of the most common causes for visits to primary care physicians, optometrists, ophthalmologists, and emergency rooms. Despite its high incidence, the treatment options for patients with conjunctival hyperemia are restricted to over-the-counter drugs that provide symptomatic relief due to short duration of action, tachyphylaxis and rebound redness. As our understanding of the immunopathological pathways causing conjunctival hyperemia expands, newer therapeutic targets are being discovered. These insights have also contributed to the development of animal models for mimicking the pathogenic changes in microvasculature causing hyperemia. Furthermore, this progress has catalyzed the development of novel therapeutics that provide efficacious, long-term relief from conjunctival hyperemia with minimal adverse effects.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.05.004},
	author = {Singh, Rohan Bir and Liu, Lingjia and Yung, Ann and Anchouche, Sonia and Mittal, Sharad K and Blanco, Tomas and Dohlman, Thomas H and Yin, Jia and Dana, Reza}
}
@article {1667701,
	title = {Vaccine-Associated Uveitis after COVID-19 Vaccination: Vaccine Adverse Event Reporting System Database Analysis},
	journal = {Ophthalmology},
	volume = {130},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {179-186},
	abstract = {PURPOSE: To assess the risk of vaccine-associated uveitis (VAU) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and evaluate uveitis onset interval and clinical presentations in the patients. DESIGN: A retrospective study from December 11, 2020, to May 9, 2022, using the Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. PARTICIPANTS: Patients diagnosed with VAU after administration of BNT162b2 (Pfizer-BioNTech, Pfizer Inc/BioNTech SE), mRNA-1273 (Moderna, Moderna Therapeutics Inc), and Ad26.COV2.S (Janssen, Janssen Pharmaceuticals) vaccine worldwide. METHODS: A descriptive analysis of the demographics, clinical history, and presentation was performed. We evaluated the correlation among the 3 vaccines and continuous and categorical variables. A post hoc analysis was performed between uveitis onset interval after vaccination and age, dose, and vaccine type. Finally, a 30-day risk analysis for VAU onset postvaccination was performed. MAIN OUTCOME MEASURES: The estimated global crude reporting rate, observed to expected ratio of VAU in the United States, associated ocular and systemic presentations, and onset duration. RESULTS: A total of 1094 cases of VAU were reported from 40 countries with an estimated crude reporting rate (per million doses) of 0.57, 0.44, and 0.35 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The observed to expected ratio of VAU was comparable for BNT162b2 (0.023), mRNA-1273 (0.025), and Ad26.COV2.S (0.027). Most cases of VAU were reported in patients who received BNT162b2 (n\&nbsp;= 853, 77.97\%). The mean age of patients with VAU was 46.24 {\textpm} 16.93 years, and 68.65\% (n\&nbsp;= 751) were women. Most cases were reported after the first dose (n\&nbsp;= 452, 41.32\%) and within the first week (n\&nbsp;= 591, 54.02\%) of the vaccination. The onset interval for VAU was significantly longer in patients who received mRNA-1273 (21.22 {\textpm} 42.74 days) compared with BNT162b2 (11.42 {\textpm} 23.16 days) and rAd26.COV2.S (12.69 {\textpm} 16.02 days) vaccines (P \&lt; 0.0001). The post hoc analysis revealed a significantly shorter interval of onset for the BNT162b2 compared with the mRNA 1273 vaccine (P \&lt; 0.0001). The 30-day risk analysis showed a significant difference among the 3 vaccines (P \&lt; 0.0001). CONCLUSIONS: The low crude reporting rate and observed to expected ratio suggest a low safety concern for VAU. This study provides insights into a possible temporal association between reported VAU events and SARS-CoV-2 vaccines; however, further investigations are required to delineate the associated immunological mechanisms.},
	keywords = {2019-nCoV Vaccine mRNA-1273, Ad26COVS1, Adult, BNT162 Vaccine, COVID-19, COVID-19 Vaccines, Female, Humans, Male, Middle Aged, Retrospective Studies, SARS-CoV-2, Uveitis, Vaccination, Vaccines},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.08.027},
	author = {Singh, Rohan Bir and Parmar, Uday Pratap Singh and Kahale, Francesca and Agarwal, Aniruddha and Tsui, Edmund}
}
@article {1333937,
	title = {Herpes simplex virus keratitis mimicking Acanthamoeba keratitis: a clinicopathological correlation},
	journal = {BMJ Case Rep},
	volume = {2018},
	year = {2018},
	month = {2018 Sep 19},
	abstract = {A 36-year-old male, soft contact lens wearer was referred by his primary ophthalmologist for corneal ulcer of the right eye (OD), which was persistent despite topical fluoroquinolone therapy for 1 month. A ring-shaped infiltrate typically seen in Acanthamoeba infection was noted, and topical therapy with chlorhexidine and polyhexamethylene biguanide was initiated. However, the patient{\textquoteright}s condition deteriorated over the next several weeks; thus, diagnostic and therapeutic penetrating keratoplasty was performed. The postoperative immunohistochemical analysis suggested a diagnosis of herpes simplex virus (HSV) keratitis. The patient ultimately improved after initiation of oral valacyclovir following penetrating keratoplasty. We report a case of a commonly encountered clinical entity, HSV keratitis, with an atypical clinical presentation, masquerading as Acanthamoeba keratitis.},
	issn = {1757-790X},
	doi = {10.1136/bcr-2018-226100},
	author = {Singh, Rohan Bir and Batta, Priti}
}
@article {1647873,
	title = {Atezolizumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis and Takotsubo cardiomyopathy},
	journal = {BMJ Case Rep},
	volume = {15},
	number = {7},
	year = {2022},
	month = {2022 Jul 06},
	abstract = {Atezolizumab is a humanised monoclonal IgG1 antibody that is used in treating many solid malignancies. Endocrinopathies are known but a rare adverse event of these immunotherapeutic drugs. Autoimmune diabetes induced by atezolizumab has been rarely reported in the literature. We report the case of a woman in her eighth decade with no known history of diabetes who developed new-onset autoimmune diabetes and Takotsubo cardiomyopathy due to the adverse effects of atezolizumab therapy for hepatocellular carcinoma. We also review the characteristics and outcomes of cases previously reported in the literature.},
	keywords = {Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Diabetes Mellitus, Type 1, Diabetic Ketoacidosis, Female, Humans, Liver Neoplasms, Takotsubo Cardiomyopathy},
	issn = {1757-790X},
	doi = {10.1136/bcr-2022-250662},
	author = {Singhal, Sachi and Patel, Goonja and Singh, Rohan Bir and Goyal, Aakash and Avgush, Karen and Koka, Jean}
}
@article {1761926,
	title = {Management of multi-surface ocular burns caused by molten iron},
	journal = {Trauma Case Rep},
	volume = {48},
	year = {2023},
	month = {2023 Dec},
	pages = {100925},
	abstract = {Ocular thermal burns are medical emergencies that require immediate intervention before the standard management protocol, which involves obtaining a detailed history and performing an ophthalmic examination. In this case report, we report the clinical manifestations of ocular burns caused by molten iron and the steps taken for good clinical outcomes. The patient presented with an inferior epithelial defect and limbal and lower lid ischemia at four hours post-injury. Over the course of treatment, due to non-resolving epithelial defect and increased superior lid notching, amniotic membrane transplantation (AMT) and lid repair by pentagon wedge excision were performed. Following AMT, the corneal surface completely healed with residual opacity and neovascularization. Additionally, limbal ischemia was significantly reduced with the restoration of normal lid anatomy. Corneal burns initiate a cascade of inflammatory reactions disrupting the balance between pro- and anti-angiogenic factors, leading to corneal neovascularization. The eyelid damage can lead to necrosis of tissues with eschar formation and eventually quantitative tissue loss. Therefore, timely intervention is the key to the successful management of ocular burns.},
	issn = {2352-6440},
	doi = {10.1016/j.tcr.2023.100925},
	author = {Singla, Ekta and Jha, Ujjwal Prakash and Muralidharan, Shruti and Singh, Rohan Bir and Ichhpujani, Parul}
}
@article {1522725,
	title = {Prevalence of Persistent Corneal Epithelial Defects in Chronic Ocular Graft-Versus-Host Disease},
	journal = {Am J Ophthalmol},
	volume = {218},
	year = {2020},
	month = {2020 Oct},
	pages = {296-303},
	abstract = {PURPOSE: To establish the prevalence, clinical characteristics, and risk factors for persistent corneal epithelial defects (PED) in patients with chronic ocular graft-versus-host disease (oGVHD) and to determine visual outcomes after healing. DESIGN: Retrospective cohort study. METHODS: A chart review was conducted of patients in whom chronic oGVHD was diagnosed between January 2011 and December 2018 and their demographic and clinical characteristics were collected. Data were analyzed to determine prevalence of PED, and multivariate logistic regression was performed to determine the risk factors associated with it. RESULTS: A total of 405 patients at a mean age of 60 {\textpm} 13 years in whom chronic oGVHD was diagnosed; 58\% were men. The prevalence of PED was 8.1\%. The median time for PED development after hematopoietic stem cell transplantation was approximately 24\&nbsp;months. Median time to PED resolution was 4.5\&nbsp;weeks after starting therapy. The mean best-corrected visual acuity declined by 2 lines post-PED resolution. The prevalence rates of corneal ulcer and perforation were 6.2\% and 4.0\%, respectively, over 8 years. Logistic regression analysis, used to determine factors associated with PED, showed diabetes (P\&nbsp;= .006), limbal stem cell deficiency (LSCD) (P\&nbsp;= .02), filamentary keratitis (P\&nbsp;= .02), subconjunctival fibrosis (P\&nbsp;= .02), and a higher National Institutes of Health (NIH) oGVHD score (P\&nbsp;= .01) were significant risk factors for PED development. CONCLUSIONS: The study found the prevalence rate of PED, corneal ulceration, and corneal perforation in chronic oGVHD to be 8.1\%, 6.2\%, and 4\%, respectively. Analysis showed that oGVHD patients with diabetes, LSCD, filamentary keratitis, subconjunctival fibrosis, and a high NIH score were at higher risk of developing severe corneal disease.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.05.035},
	author = {Sinha, Shruti and Singh, Rohan Bir and Dohlman, Thomas H and Wang, Mengyu and Taketani, Yukako and Yin, Jia and Dana, Reza}
}
@article {1532351,
	title = {Prevalence and Risk Factors Associated With Corneal Perforation in Chronic Ocular Graft-Versus-Host-Disease},
	journal = {Cornea},
	volume = {40},
	number = {7},
	year = {2021},
	month = {2021 Jul 01},
	pages = {877-882},
	abstract = {PURPOSE: To determine the prevalence and risk factors associated with corneal perforation in patients with chronic ocular graft-versus-host disease (oGVHD). METHODS: We reviewed the case records of 405 patients diagnosed with chronic oGVHD over 8 years at a single academic center and assessed the prevalence of corneal perforation in the cohort. We reviewed patient demographics, indication for and type of hematopoietic stem cell transplantation (HSCT), time elapsed between HSCT and perforation, and clinical characteristics including oGVHD severity scores, ocular comorbidities, and topical medications at the time of perforation. Data were analyzed to determine the characteristics of patients with corneal perforation and establish the risk factors. RESULTS: Of the 405 patients with chronic oGVHD, 15 (3.7\%) developed a corneal perforation. The mean age of patients at the time of perforation was 64 {\textpm} 11 years and 10 (67\%) were men. The median time to corneal perforation was 3.3 years post-HSCT. Although perforation occurred unilaterally in all cases, 44\% had epithelial defects and 38\% had stromal abnormalities in the contralateral eye. Of the patients with corneal perforation, 9 (60\%) had a National Institute of Health oGVHD severity score of 2 and 6 (40\%) had a score of 3. Patients with chronic oGVHD on antiglaucoma drops had a significantly higher risk of corneal perforation (P \&lt; 0.001). CONCLUSIONS: Corneal perforation is a rare but vision-threatening complication of chronic oGVHD. Our study emphasizes the need for frequent and long-term follow-up of patients with oGVHD regardless of the severity of disease. In particular, patients with chronic oGVHD on topical antiglaucoma medications should be monitored closely due to a higher risk for corneal perforation.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002526},
	author = {Sinha, Shruti and Singh, Rohan Bir and Dohlman, Thomas H and Taketani, Yukako and Yin, Jia and Dana, Reza}
}
@article {1661810,
	title = {Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {130},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {433-442},
	abstract = {PURPOSE: To review the current published literature on the utility of corneal hysteresis (CH) to assist the clinician in the diagnosis of glaucoma or in the assessment of risk for disease progression in existing glaucoma patients. METHODS: Searches of the peer-reviewed literature in the PubMed database were performed through July 2022. The abstracts of 423 identified articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 19 articles were selected, and the panel methodologist rated them for level of evidence. Eight articles were rated level I, and 5 articles were rated level II. The 6 articles rated level III were excluded. RESULTS: Corneal hysteresis is lower in patients with primary open-angle glaucoma, primary angle-closure glaucoma, pseudoexfoliative glaucoma, and pseudoexfoliation syndrome compared with normal subjects. Interpretation of low CH in patients with high intraocular pressure (IOP) or on topical hypotensive medications is complicated by the influence of these parameters on CH measurements. However, CH is also lower in treatment-na{\"\i}ve, normal-tension glaucoma patients compared with normal subjects who have a similar IOP. In addition, lower CH is associated with an increased risk of progression of glaucoma based on visual fields or structural markers in open-angle glaucoma patients, including those with apparently well-controlled IOP. CONCLUSIONS: Corneal hysteresis is lower in glaucoma patients compared with normal subjects, and lower CH is associated with an increased risk of disease progression. However, a causal relationship remains to be demonstrated. Nevertheless, measurement of CH complements current structural and functional assessments in determining disease risk in glaucoma suspects and patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Biomechanical Phenomena, Cornea, Disease Progression, Elasticity, Glaucoma, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Ophthalmology, Tonometry, Ocular, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.11.009},
	author = {Sit, Arthur J and Chen, Teresa C and Takusagawa, Hana L and Rosdahl, Jullia A and Hoguet, Ambika and Chopra, Vikas and Richter, Grace M and Ou, Yvonne and Kim, Stephen J and WuDunn, Darrell}
}
@article {836966,
	title = {Superior Limbic Keratoconjunctivitis-like Inflammation in Patients with Chronic Graft-Versus-Host Disease.},
	journal = {Ocul Surf},
	volume = {14},
	number = {3},
	year = {2016},
	month = {2016 Jul},
	pages = {393-400},
	abstract = {PURPOSE: Describe the presentation and management of superior limbic keratoconjunctivitis (SLK)-like inflammation and secondary limbal stem cell dysfunction in the setting of ocular chronic graft-versus-host disease (cGVHD). METHODS: Retrospective observational case series in a multicenter clinical practice. Participants were 13 patients (26 eyes) with ocular cGVHD and SLK-like inflammation presenting to the University of Illinois at Chicago and BostonSight{\textregistered} between January 1, 2009 and July 1,\&nbsp;2013. MAIN OUTCOME MEASURES: 1) Reversal or worsening of SLK, and 2) development of limbal stem cell dysfunction. RESULTS: All eyes showed evidence of SLK-like inflammation and superior limbal stem cell dysfunction manifested by conjunctival injection and superior conjunctival and corneal staining. In addition to aggressive lubrication, management strategies for SLK included topical steroids (20/26), punctal occlusion (18/26), topical cyclosporine (24/26), autologous serum tears (12/26), therapeutic soft contact lens (13/26 eyes) and scleral lenses (4/26 eyes). SLK and limbal stem cell\&nbsp;dysfunction were reversed in 23/26 eyes. Three eyes of two patients with long-standing disease demonstrated frank\&nbsp;limbal stem cell deficiency (LSCD) and corneal pannus,\&nbsp;with one patient requiring multiple reconstructive surgical procedures. CONCLUSIONS: SLK-like inflammation is an under-recognized condition in patients with severe dry eyes secondary to ocular cGVHD. Untreated SLK can potentially lead to permanent LSCD over time. Early recognition and management of SLK in ocular cGVHD can improve vision, reverse signs, and may prevent these long-term consequences.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2016.04.003},
	author = {Sivaraman, Kavitha R and Jivrajka, Renu V and Soin, Ketki and Bouchard, Charles S and Movahedan, Asadolah and Shorter, Ellen and Jain, Sandeep and Jacobs, Deborah S and Djalilian, Ali R}
}
@article {1688366,
	title = {Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial},
	journal = {Clin Nutr},
	volume = {42},
	number = {6},
	year = {2023},
	month = {2023 Jun},
	pages = {962-971},
	abstract = {BACKGROUND \&amp; AIM: Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources. METHODS: Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born \&lt;28 weeks of gestation (n\&nbsp;=\&nbsp;204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50\&nbsp;mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol\%) and absolute concentration (μmol l-1) units. RESULTS: Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p\&nbsp;\&lt;\&nbsp;0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) μmol l-1, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p\&nbsp;\&lt;\&nbsp;0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p\&nbsp;\&lt;\&nbsp;0.05). CONCLUSIONS: Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, identifier: NCT03201588.},
	keywords = {Arachidonic Acid, Cohort Studies, Docosahexaenoic Acids, Fatty Acids, Humans, Infant, Infant, Extremely Premature, Infant, Newborn, Phospholipids},
	issn = {1532-1983},
	doi = {10.1016/j.clnu.2023.04.020},
	author = {Sj{\"o}bom, Ulrika and Andersson, Mats X and Pivodic, Aldina and Lund, Anna-My and Vanpee, Mireille and Hansen-Pupp, Ingrid and Ley, David and Wackernagel, Dirk and S{\"a}vman, Karin and Smith, Lois E H and L{\"o}fqvist, Chatarina and Hellstr{\"o}m, Ann and Nilsson, Anders K}
}
@article {647346,
	title = {Secondary allergic T cell responses are regulated by dendritic cell-derived thrombospondin-1 in the setting of allergic eye disease.},
	journal = {J Leukoc Biol},
	volume = {100},
	number = {2},
	year = {2016},
	month = {2016 Aug},
	pages = {371-80},
	abstract = {Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin-1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with na{\"\i}ve T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell-derived thrombospondin-1 expression as a factor in allergic eye disease severity.},
	issn = {1938-3673},
	doi = {10.1189/jlb.3A0815-357RR},
	author = {Smith, R E and Reyes, N J and Khandelwal, P and Schlereth, S L and Lee, H S and Masli, S and Saban, D R}
}
@article {1417577,
	title = {Proceedings of the Association for Research in Vision and Ophthalmology and Champalimaud Foundation Ocular Oncogenesis and Oncology Conference},
	journal = {Transl Vis Sci Technol},
	volume = {8},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {9},
	abstract = {The 2018 Ocular Oncogenesis and Oncology Conference was held through a partnership of the Association for Research in Vision and Ophthalmology (ARVO) and the Champalimaud Foundation. Twenty-one experts from international ocular oncology centers, from the Champalimaud Clinical Centre and the Champalimaud Foundation Cancer Research Program, and from patient advocacy organizations, delivered lectures on subjects that ranged from global ocular oncology, to basic research in mechanisms of ocular malignancy, to clinical research in ocular cancers, and to anticipated future developments in the area. The scientific program of the conference covered a broad range of ocular tumors-including uveal melanoma, retinoblastoma, ocular surface tumors, and adnexal and intraocular lymphomas-and pathogenesis and management were deliberated in the context of the broader systemic cancer discipline. In considering the latest basic and clinical research developments in ocular oncogenesis and oncology, and providing the opportunity for cross-talk between ocular cancer biologists, systemic cancer biologists, ocular oncologists, systemic oncologists, patients, and patient advocates, the forum generated new knowledge and novel insights for the field. This report summarizes the content of the invited talks at the 2018 ARVO-Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.},
	issn = {2164-2591},
	doi = {10.1167/tvst.8.1.9},
	author = {Smith, Justine R and Pe{\textquoteright}er, Jacob and Belfort, Rubens N and Cardoso, Fatima and Carvajal, Richard D and Carvalho, Carlos and Coupland, Sarah E and Desjardins, Laurence and Francis, Jasmine H and Gallie, Brenda L and Gombos, Dan S and Grossniklaus, Hans E and Heegaard, Steffen and Jager, Martine J and Kaliki, Swathi and Ksander, Bruce R and Maeurer, Markus and Moreno, Eduardo and Pulido, Jose S and Ryll, Bettina and Singh, Arun D and Zhao, Junyang and Parreira, Ant{\'o}nio and Wilson, David J and O{\textquoteright}Brien, Joan M}
}
@article {1363205,
	title = {The biology of retinopathy of prematurity: how knowledge of pathogenesis guides treatment},
	journal = {Clin Perinatol},
	volume = {40},
	number = {2},
	year = {2013},
	month = {2013 Jun},
	pages = {201-14},
	abstract = {Retinopathy of prematurity occurs because the retina of a preterm infant at birth is incompletely vascularized, and if the postnatal environment does not match the in utero environment that supported retinal development, the vessels and neural retina will not grow normally. Risk factors determined from many clinical studies and animal studies fall into 2 categories: prenatal factors and postnatal factors.},
	keywords = {Erythropoietin, Humans, Infant, Infant, Newborn, Infant, Premature, Insulin-Like Growth Factor I, Oxygen, Retina, Retinopathy of Prematurity, Vascular Endothelial Growth Factor A},
	issn = {1557-9840},
	doi = {10.1016/j.clp.2013.02.002},
	author = {Smith, Lois E and Hard, Anna-Lena and Hellstr{\"o}m, Ann}
}
@article {1402588,
	title = {Development of a Retinopathy of Prematurity Activity Scale and Clinical Outcome Measures for Use in Clinical Trials},
	journal = {JAMA Ophthalmol},
	year = {2018},
	month = {2018 Dec 13},
	abstract = {Importance: To facilitate drug and device development for neonates, the International Neonatal Consortium brings together key stakeholders, including pharmaceutical companies, practitioners, regulators, funding agencies, scientists, and families, to address the need for objective, standardized clinical trial outcome measurements to fulfill regulatory requirements. Retinopathy of prematurity (ROP) is a disease that affects preterm neonates. The current International Classification of Retinopathy of Prematurity does not take into account all of the characteristics of ROP and does not adequately discriminate small changes in disease after treatment. These factors are critical for evaluating outcomes in clinical trials. Observations: There is need for an updated ROP acute disease activity and structure scale as well as end-stage structure and ophthalmologic outcome measures designed for use at different ages. The scale and measures, based on current diagnostic methods and treatments, could be used as a guideline for clinical intervention trials. The scale is intended to be validated against retrospective data and revised for use in future trials. An iterative revision process can be accomplished if new measures are added to clinical trials and evaluated at the end of each trial for prognostic value. The new measures would then be incorporated into a new version of the activity scale and the outcome measures revised. Conclusions and Relevance: An ROP activity scale and outcome measures to obtain the most robust and discriminatory data for clinical trials are needed. The scales should be dynamic and modified as knowledge and imaging modalities improve and then validated using data from well-documented clinical trials. This approach is relevant to improving clinical trial data quality.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.5984},
	author = {Smith, Lois E H and Hellstr{\"o}m, Ann and Stahl, Andreas and Fielder, Alistair and Chambers, Wiley and Moseley, Jane and Toth, Cynthia and Wallace, David and Darlow, Brian A and Aranda, Jacob V and Hallberg, Boubou and Davis, Jonathan M and Retinopathy of Prematurity Workgroup of the International Neonatal Consortium}
}
@article {1439864,
	title = {Machine Learning in the Detection of the Glaucomatous Disc and Visual Field},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 May 27},
	pages = {1-11},
	abstract = {Glaucoma is the leading cause of irreversible blindness worldwide. Early detection is of utmost importance as there is abundant evidence that early treatment prevents disease progression, preserves vision, and improves patients{\textquoteright} long-term quality of life. The structure and function thresholds that alert to the diagnosis of glaucoma can be obtained entirely via digital means, and as such, screening is well suited to benefit from artificial intelligence and specifically machine learning. This paper reviews the concepts and current literature on the use of machine learning for detection of the glaucomatous disc and visual field.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620801},
	author = {Smits, David J and Tobias Elze and Wang, Haobing and Pasquale, Louis R}
}
@article {1626105,
	title = {Orbital Radiation for Thyroid Eye Disease: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	year = {2021},
	month = {2021 Dec 08},
	abstract = {PURPOSE: To review the current literature on the safety and efficacy of orbital radiation for the management of thyroid eye disease (TED). METHODS: A literature search was conducted last in February 2021 of the PubMed database to identify all articles published in the English language on original research that assessed the effect of orbital radiation on TED. The search identified 55 articles, and 18 met the inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study, and all of them were rated level III. RESULTS: Two large retrospective studies demonstrated the efficacy of radiation treatment, with or without corticosteroid use, in preventing or treating compressive optic neuropathy (CON). Three studies highlighted the role of orbital radiation therapy (RT) to facilitate the tapering of corticosteroids. Several other studies showed a possible role for RT to improve diplopia and soft tissue signs. CONCLUSIONS: Although no level I or level II evidence exists, the best available evidence suggests that orbital radiation, used with or without corticosteroids, is efficacious in preventing CON, improving motility restriction, and decreasing clinical activity in TED. Orbital radiation also may facilitate a corticosteroid taper. Together, these studies show that RT seems to modify the active phase of TED. Short-term risks of orbital radiation are minor, but long-term outcome data are lacking.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.10.025},
	author = {Sobel, Rachel K and Aakalu, Vinay K and Vagefi, M Reza and Foster, Jill A and Tao, Jeremiah P and Freitag, Suzanne K and Wladis, Edward J and McCulley, Timothy J and Yen, Michael T}
}
@article {1549028,
	title = {Risk of Noninfectious Uveitis with Female Hormonal Therapy in a Large Healthcare Claims Database},
	journal = {Ophthalmology},
	volume = {127},
	number = {11},
	year = {2020},
	month = {2020 11},
	pages = {1558-1566},
	abstract = {PURPOSE: To determine if female hormonal therapy (FHT) increases the incidence of noninfectious uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Women exposed to FHT and matched women unexposed to FHT enrolled in a national insurance plan. METHODS: Estimation of noninfectious uveitis incidence used multivariable Cox proportional hazards regression. To account for differences between the exposed and unexposed cohorts, a propensity score for being prescribed FHT was created using logistic regression, and inverse probability of treatment weighting was performed. MAIN OUTCOME MEASURES: Incidence of noninfectious uveitis. For the primary outcome, incident noninfectious uveitis was defined as a new diagnosis code for noninfectious uveitis followed by a second instance of a noninfectious uveitis code within 120 days. For the alternative outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the uveitis diagnosis code was used instead of the second uveitis diagnosis code. RESULTS: There were 217 653 women exposed to FHT and 928 408 women not unexposed to FHT. For the primary outcome, the hazard ratio (HR) for incident noninfectious uveitis was not significantly different between the FHT and unexposed cohorts (HR, 0.99; 95\% confidence interval [CI], 0.83-1.17; P\&nbsp;= 0.87). With the alternative outcome definition, the FHT cohort was more likely to develop uveitis (HR, 1.21; 95\% CI, 1.04-1.41; P\&nbsp;= 0.01). When examined by anatomic subtype, for anterior uveitis there was a greater likelihood of incident uveitis in the exposed cohort (HR, 1.23; 95\% CI, 1.05-1.45; P\&nbsp;= 0.01) for the alternative outcome definition but not for the primary outcome. With age stratification, women exposed to FHT aged >=45 years at the time of FHT prescription were more likely to develop uveitis (HR, 1.23; 95\% CI, 1.03-1.47; P\&nbsp;= 0.03) for the alternative outcome definition. A similar HR (1.22) was seen for women aged <=44 years at the time of prescription, but this association did not meet statistical significance (P\&nbsp;= 0.20). CONCLUSIONS: Exposure to FHT increases the rate of incident noninfectious uveitis when uveitis is defined on the basis of both diagnostic codes and documentation of corticosteroid treatment. However, the risk is modest and FHT is likely safe with regard to noninfectious uveitis risk in the majority of patients exposed to these drugs.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.04.034},
	author = {Sobrin, Lucia and Yu, Yinxi and Susarla, Gayatri and Chan, Weilin and Xia, Tian and Kempen, John H and Hubbard, Rebecca A and VanderBeek, Brian L}
}
@article {1586180,
	title = {Risk of Non-infectious Uveitis with Metformin Therapy in a Large Healthcare Claims Database},
	journal = {Ocul Immunol Inflamm},
	year = {2021},
	month = {2021 Mar 08},
	pages = {1-7},
	abstract = {PURPOSE: To determine if metformin is associated with noninfectious uveitis (NIU). METHODS: Patients in an insurance claims database who initiated metformin (n = 359,139) or other oral anti-diabetic medications (n = 162,847) were followed for NIU development. Both cohort and case-control analyses were performed to assess differing exposure lengths using Cox and conditional logistic regression, respectively. RESULTS: The hazard ratio (HR) for incident NIU was not significantly different between the metformin and non-metformin cohorts [HR = 1.19, 95\% Confidence Interval (CI): 0.92-1.54, = .19]. The case control analysis similarly showed no association between any metformin use 2 years before the outcome date and NIU [odds ratio (OR) = 0.64, 95\% CI: 0.39-1.04, = .07]. However, there was a protective 20 association between cumulative metformin duration [(445-729 days) adjusted OR (aOR) = 0.49, 95\% CI: 0.27-0.90, = .02] and dosage (\&gt;390,000 mg aOR = 0.44, 95\% CI: 0.25-0.78, = .001) compared with no metformin use. CONCLUSIONS: Our results suggest metformin use for longer durations may be protective of NIU onset.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2021.1872650},
	author = {Sobrin, Lucia and Yu, Yinxi and Han, Samuel and Susarla, Gayatri and Kempen, John H and Hubbard, Rebecca A and VanderBeek, Brian L}
}
@article {1364549,
	title = {Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes},
	journal = {Ophthalmology},
	volume = {119},
	number = {9},
	year = {2012},
	month = {2012 Sep},
	pages = {1874-85},
	abstract = {PURPOSE: To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. DESIGN: Sibling correlation study and genome-wide association study (GWAS). PARTICIPANTS: For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. METHODS: Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. MAIN OUTCOME MEASURES: Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. RESULTS: The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2 {\texttimes} 10(-5)), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3 {\texttimes} 10(-9)), which was confirmed in the replication samples (OR, 1.38; P = 7.4 {\texttimes} 10(-14) for combined discovery and replication analysis). CONCLUSIONS: Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies.},
	keywords = {Choroidal Neovascularization, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Geographic Atrophy, High-Temperature Requirement A Serine Peptidase 1, Humans, Macular Degeneration, Male, Polymorphism, Single Nucleotide, Proteins, Risk Factors, Serine Endopeptidases, Siblings},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2012.03.014},
	author = {Sobrin, Lucia and Ripke, Stephan and Yu, Yi and Fagerness, Jesen and Bhangale, Tushar R and Tan, Perciliz L and Souied, Eric H and Buitendijk, Gabri{\"e}lle H S and Merriam, Joanna E and Richardson, Andrea J and Raychaudhuri, Soumya and Reynolds, Robyn and Chin, Kimberly A and Lee, Aaron Y and Leveziel, Nicolas and Zack, Donald J and Campochiaro, Peter and Smith, R Theodore and Barile, Gaetano R and Hogg, Ruth E and Chakravarthy, Usha and Behrens, Timothy W and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and Vingerling, Johannes R and Brantley, Milam A and Baird, Paul N and Klaver, Caroline C W and Allikmets, Rando and Katsanis, Nicholas and Graham, Robert R and Ioannidis, John P A and Daly, Mark J and Seddon, Johanna M}
}
@article {1195226,
	title = {Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study},
	journal = {Diabetes},
	volume = {66},
	number = {12},
	year = {2017},
	month = {2017 Dec},
	pages = {3130-3141},
	abstract = {Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.},
	keywords = {Aged, Diabetic Retinopathy, Female, Genome-Wide Association Study, Humans, Lipids, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk},
	issn = {1939-327X},
	doi = {10.2337/db17-0398},
	author = {Sobrin, Lucia and Chong, Yong He and Fan, Qiao and Gan, Alfred and Stanwyck, Lynn K and Kaidonis, Georgia and Craig, Jamie E and Kim, Jihye and Liao, Wen-Ling and Huang, Yu-Chuen and Lee, Wen-Jane and Hung, Yi-Jen and Guo, Xiuqing and Hai, Yang and Ipp, Eli and Pollack, Samuela and Hancock, Heather and Price, Alkes and Penman, Alan and Mitchell, Paul and Liew, Gerald and Smith, Albert V and Gudnason, Vilmundur and Tan, Gavin and Klein, Barbara E K and Kuo, Jane and Li, Xiaohui and Christiansen, Mark W and Psaty, Bruce M and Sandow, Kevin and Asian Genetic Epidemiology Network Consortium and Jensen, Richard A and Klein, Ronald and Cotch, Mary Frances and Wang, Jie Jin and Jia, Yucheng and Chen, Ching J and Chen, Yii-Der Ida and Rotter, Jerome I and Tsai, Fuu-Jen and Hanis, Craig L and Burdon, Kathryn P and Wong, Tien Yin and Cheng, Ching-Yu}
}
@article {1645456,
	title = {Erratum to Gene Set Enrichment Analyses Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy. Am J Ophthalmol 2022;233:111-123},
	journal = {Am J Ophthalmol},
	year = {2022},
	month = {2022 Jun 01},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.03.002},
	author = {Sobrin, Lucia and Susarla, Gayatri and Stanwyck, Lynn and Rouhana, John M and Li, Ashley and Pollack, Samuela and Igo, Robert P and Jensen, Richard A and Li, Xiaohui and Ng, Maggie C Y and Smith, Albert V and Kuo, Jane Z and Taylor, Kent D and Freedman, Barry I and Bowden, Donald W and Penman, Alan and Chen, Ching J and Craig, Jamie E and Adler, Sharon G and Chew, Emily Y and Cotch, Mary Frances and Yaspan, Brian and Mitchell, Paul and Wang, Jie Jin and Klein, Barbara E K and Wong, Tien Y and Rotter, Jerome I and Burdon, Kathyrn P and Iyengar, Sudha K and Segr{\`e}, Ayellet V}
}
@article {1593864,
	title = {Decreased risk of non-infectious anterior uveitis with statin therapy in a large healthcare claims database},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {259},
	number = {9},
	year = {2021},
	month = {2021 Sep},
	pages = {2783-2793},
	abstract = {PURPOSE: The purpose of this study is to determine if statin therapy decreases the incidence of non-infectious uveitis (NIU) using a retrospective cohort study. METHODS: Patients enrolled in a national insurance plan who initiated statin (n = 711,734, statin cohort) or other lipid-lowering therapy (n = 148,044, non-statin cohort) were observed for NIU development. Incident NIU in the primary analysis was defined as a new diagnosis code for NIU followed by a second instance of a NIU code within 120\&nbsp;days. For the secondary outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120\&nbsp;days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Estimation of NIU incidence used multivariable Cox proportional hazards regression. The proportional hazards assumption was satisfied by creating two time periods of analysis, <= 150 and \&gt; 150\&nbsp;days. Subanalyses were performed by anatomic subtype. RESULTS: Overall, the primary outcome occurred 541 times over 690,465 person-years in the statin cohort and 103 times over 104,301 person-years in the non-statin cohort. No associations were seen in the <= 150-day analyses (p \&gt; 0.20 for all comparisons). However, after 150\&nbsp;days, the statin cohort was less likely to develop any uveitis [hazard ratio (HR) = 0.70, 95\% confidence interval (CI): 0.51-0.97, P = 0.03] in the primary outcome analysis, but did not meet significance for the secondary outcome (HR = 0.85, 95\% CI: 0.63-1.15, P = 0.30). Similarly, in the anatomic subtype analysis, after 150\&nbsp;days, the statin cohort was less likely to develop anterior uveitis (HR = 0.67, 95\% CI: 0.47-0.97, P = 0.03) in the primary analysis, but the association did not reach significance for the secondary outcome (HR = 0.82, 95\% CI: 0.56-1.20, P = 0.31). CONCLUSION: Our results suggest that statin therapy for \&gt; 150\&nbsp;days decreases the incidence of NIU.},
	keywords = {Delivery of Health Care, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Retrospective Studies, Uveitis, Uveitis, Anterior},
	issn = {1435-702X},
	doi = {10.1007/s00417-021-05243-8},
	author = {Sobrin, Lucia and Yu, Yinxi and Han, Samuel and Susarla, Gayatri and Kempen, John H and Hubbard, Rebecca A and VanderBeek, Brian L}
}
@article {1364550,
	title = {Longitudinal validation of hemoglobin A(1c) criteria for diabetes diagnosis: risk of retinopathy},
	journal = {Diabetes},
	volume = {61},
	number = {12},
	year = {2012},
	month = {2012 Dec},
	pages = {3074-5},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Glycated Hemoglobin A, Humans},
	issn = {1939-327X},
	doi = {10.2337/db12-1226},
	author = {Sobrin, Lucia}
}
@article {1504053,
	title = {Case 14-2020: A 37-Year-Old Man with Joint Pain and Eye Redness},
	journal = {N Engl J Med},
	volume = {382},
	number = {18},
	year = {2020},
	month = {2020 04 30},
	pages = {1750-1758},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc1909623},
	author = {Sobrin, Lucia and Stone, John H and Huang, Ambrose J and Niles, John L and Nazarian, Rosalynn M}
}
@article {1307463,
	title = {Progress Toward Precisely Diagnosing Autoimmune Retinopathy},
	journal = {Am J Ophthalmol},
	volume = {188},
	year = {2018},
	month = {2018 Apr},
	pages = {xiv-xv},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.01.002},
	author = {Sobrin, Lucia}
}
@article {1580506,
	title = {Angiotensin Converting Enzyme-Inhibitors and Incidence of Non-infectious Uveitis in a Large Healthcare Claims Database},
	journal = {Ophthalmic Epidemiol},
	year = {2021},
	month = {2021 Feb 23},
	pages = {1-6},
	abstract = {: To determine if angiotensin converting enzyme-inhibitors (ACE-I) alter the incidence of non-infectious uveitis (NIU). Patients in a large healthcare claims database who initiated ACE-I (n\&nbsp;=\&nbsp;695,557) were compared to patients who initiated angiotensin receptor blockers (ARB, n =\&nbsp;354,295). A second comparison was also made between patients who initiated ACE-I (n\&nbsp;=\&nbsp;505,958) and those who initiated beta-blockers (BB, n =\&nbsp;538,109). The primary outcome was incident NIU defined as a first diagnosis code for NIU followed by a second instance of a NIU code within 120\&nbsp;days. For the secondary outcome, a corticosteroid prescription or code for an ocular corticosteroid injection within 120\&nbsp;days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Data were analyzed using Cox regression modeling with inverse probability of treatment weighting (IPTW). Sub-analyses were performed by anatomic subtype. When comparing ACE-I to ARB initiators, the hazard ratio (HR) for incident NIU was not significantly different for the primary outcome [HR\&nbsp;=\&nbsp;0.95, 95\% Confidence Interval (CI): 0.85-1.07, =\&nbsp;.41] or secondary outcome [HR\&nbsp;=\&nbsp;0.96, 95\% CI: 0.86-1.07, =\&nbsp;.44]. Similarly, in the ACE-I and BB initiators comparison, the HR for incident NIU was not significantly different comparing ACE-I and BB initiators for either outcome definition or any of the NIU anatomical subtypes. Our results suggest there is no evidence that ACE-I have a protective effect on NIU.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2021.1887284},
	author = {Sobrin, Lucia and Yu, Yinxi and Li, Ashley and Kempen, John H and Hubbard, Rebecca A and VanderBeek, Brian L}
}
@article {1632298,
	title = {Not All Genes Are Created Equal in Age-Related Macular Degeneration},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {3},
	year = {2022},
	month = {2022 Mar 01},
	pages = {260-261},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.6069},
	author = {Sobrin, Lucia and Yang, Janine Y}
}
@article {1351190,
	title = {Nature and nurture- genes and environment- predict onset and progression of macular degeneration},
	journal = {Prog Retin Eye Res},
	volume = {40},
	year = {2014},
	month = {2014 May},
	pages = {1-15},
	abstract = {Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages. Both environmental and genetic factors contribute to the development of this disease. Among environmental factors, smoking, obesity and dietary factors including antioxidants and dietary fat intake influence onset and progression of AMD. There are also several lines of evidence that link cardiovascular, immune and inflammatory biomarkers to AMD. The genetic etiology of AMD has been and continues to be an intense and fruitful area of investigation. Genome-wide association studies have revealed numerous common variants associated with AMD and sequencing is increasing our knowledge of how rare genetic variants strongly impact disease. Evidence for interactions between environmental, therapeutic and genetic factors is emerging and elucidating the mechanisms of this interplay remains a major challenge in the field. Genotype-phenotype associations are evolving. The knowledge of non-genetic, modifiable risk factors along with information about heritability and genetic risk variants for this disease acquired over the past 25 years have greatly improved patient management and our ability to predict which patients will develop or progress to advanced forms of AMD. Personalized medicine and individualized prevention and treatment strategies may become a reality in the near future.},
	keywords = {Age of Onset, Disease Progression, DNA Methylation, Gene-Environment Interaction, Humans, Life Style, Macular Degeneration, Prevalence, Risk Factors},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2013.12.004},
	author = {Sobrin, Lucia and Seddon, Johanna M}
}
@article {1517180,
	title = {Factors Predictive of Remission of Chronic Anterior Uveitis},
	journal = {Ophthalmology},
	volume = {127},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {826-834},
	abstract = {PURPOSE: To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with anterior uveitis of longer than 3 months{\textquoteright} duration followed up at United States tertiary uveitis care facilities. METHODS: Estimation of remission incidence and identification of associated predictors used survival analysis. MAIN OUTCOME MEASURES: Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis while off treatment at all visits spanning an interval of at least 90 days or-for patients who did not return for follow-up after 90 days-remaining inactive without receiving suppressive medications at all of the last visits. Association of factors potentially predictive of medication-free remission was also studied. RESULTS: Two thousand seven hundred ninety-five eyes of 1634 patients with chronic anterior uveitis were followed up over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7\% (95\% confidence interval [CI], 30.4\%-35.2\%). Baseline clinical factors predictive of reduced remission incidence included longer duration of uveitis at presentation (for 2 to 5 years vs. less than 6 months: adjusted hazard ratio [aHR], 0.61; 95\% CI, 0.44-0.83), bilateral uveitis (aHR, 0.75; 95\% CI, 0.59-0.96), prior cataract surgery (aHR, 0.70; 95\% CI 0.56-0.88), and glaucoma surgery (aHR, 0.63; 95\% CI, 0.45-0.90). Two time-updated characteristics were also predictive of reduced remission incidence: keratic precipitates (aHR, 0.36; 95\% CI, 0.21-0.60) and synechiae (aHR, 0.62; 95\% CI, 0.41-0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy were also associated with reduced remission incidence. Older age at presentation was associated with higher incidence of remission (for age >=40 years vs. \&lt;40 years: aHR, 1.29; 95\% CI, 1.02-1.63). CONCLUSIONS: Approximately one third of patients with chronic anterior uveitis remit within 5 years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict reduced remission incidence; patients with these factors should be managed taking into account the higher probability of a longer disease course.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.11.020},
	author = {Sobrin, Lucia and Pistilli, Maxwell and Dreger, Kurt and Kothari, Srishti and Khachatryan, Naira and Artornsombudh, Pichaporn and Pujari, Siddharth S and Foster, C Stephen and Jabs, Douglas A and Nussenblatt, Robert B and Rosenbaum, James T and Levy-Clarke, Grace A and Sen, H Nida and Suhler, Eric B and Thorne, Jennifer E and Bhatt, Nirali P and Kempen, John H and Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Research Group}
}
@article {1309968,
	title = {Association of Hypovitaminosis D With Increased Risk of Uveitis in a Large Health Care Claims Database},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {5},
	year = {2018},
	month = {2018 May 01},
	pages = {548-552},
	abstract = {Importance: Understanding the role of vitamin D-which regulates inflammatory responses-in noninfectious uveitis (an inflammatory disease) may provide insight into treatment and prevention of this disease.

Objective: To investigate whether there is an association between hypovitaminosis D and incident noninfectious uveitis.

Design, Setting, and Participants: In a retrospective case-control study, data from a health care claims database containing deidentified medical claims from a large private insurer were used to identify 558 adults enrolled from January 1, 2000, to December 31, 2016, who received a diagnosis of noninfectious uveitis from an eye care clinician (with receipt of a confirmatory diagnosis within 120 days of the initial diagnosis) and who had a vitamin D level measured within 1 year before the first diagnosis. Exclusion criteria included having systemic disease or receiving medication known to lower vitamin D levels, having undergone intraocular surgery, and having infectious uveitis. Each case patient was matched with 5 controls on the basis of age, sex, race/ethnicity, and index date (2790 controls). The controls had vitamin D level determined either within 1 year before or within 6 months after receiving an eye examination with normal findings. Multiple logistic regression models were used to examine the association between hypovitaminosis D and noninfectious uveitis.

Main Outcomes and Measures: The primary, prespecified analysis assessed the association of noninfectious uveitis with hypovitaminosis D (vitamin D level <=20 ng/mL).

Results: The 558 cases and 2790 controls were matched on age, and each group had a mean (SD) age of 58.9 (14.7) years. Among the cohort of 3348 patients, 2526 (75.4\%) were female, and the racial/ethnic distribution in the matched samples was 2022 (60.4\%) white, 552 (16.5\%) black, 402 (12.0\%) Hispanic, 162 (4.8\%) Asian, and 210 (6.3\%) unknown. Patients with normal vitamin D levels had 21\% lower odds of having noninfectious uveitis than patients with low vitamin D levels (odds ratio [OR], 0.79; 95\% CI, 0.62-0.99; P = .04). In a race-stratified analysis, an association between vitamin D and uveitis was found in black patients (OR, 0.49; 95\% CI, 0.30-0.80; P = .004) and was qualitatively similar but nonsignificant in white patients (OR, 0.87; 95\% CI, 0.62-1.21; P = .40) and Hispanic patients (OR, 0.60; 95\% CI, 0.33-1.10; P = .10).

Conclusions and Relevance: This and other reports have found an association between hypovitaminosis D and noninfectious uveitis. However, these studies cannot establish a causal relationship. Prospective studies are warranted to evaluate whether hypovitaminosis D causes increased risk of uveitis and the role of vitamin D supplementation in prevention and treatment of uveitis.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2018.0642},
	author = {Sobrin, Lucia and Stanwyck, Lynn K and Pan, Wei and Hubbard, Rebecca A and Kempen, John H and VanderBeek, Brian L}
}
@article {1598031,
	title = {Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy},
	journal = {Am J Ophthalmol},
	volume = {233},
	year = {2022},
	month = {2022 01},
	pages = {111-123},
	abstract = {To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was \&lt;.05. RESULTS: Five gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P \&lt; .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr\&nbsp;=\&nbsp;.014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr\&nbsp;=\&nbsp;.022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P\&nbsp;=\&nbsp;.032); apoptosis (1.53-fold enrichment, P\&nbsp;=\&nbsp;.041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr\&nbsp;=\&nbsp;.049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P\&nbsp;=\&nbsp;.0001). CONCLUSIONS: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.},
	keywords = {Diabetes Mellitus, Type 2, Diabetic Retinopathy, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.06.014},
	author = {Sobrin, Lucia and Susarla, Gayatri and Stanwyck, Lynn and Rouhana, John M and Li, Ashley and Pollack, Samuela and Igo, Robert P and Jensen, Richard A and Li, Xiaohui and Ng, Maggie C Y and Smith, Albert V and Kuo, Jane Z and Taylor, Kent D and Freedman, Barry I and Bowden, Donald W and Penman, Alan and Chen, Ching J and Craig, Jamie E and Adler, Sharon G and Chew, Emily Y and Cotch, Mary Frances and Yaspan, Brian and Mitchell, Paul and Wang, Jie Jin and Klein, Barbara E K and Wong, Tien Y and Rotter, Jerome I and Burdon, Kathyrn P and Iyengar, Sudha K and Segr{\`e}, Ayellet V}
}
@article {1603859,
	title = {Dexamethasone-Eluting Contact Lens for the Prevention of Postphotorefractive Keratectomy Scar in a New Zealand White Rabbit Model},
	journal = {Cornea},
	volume = {40},
	number = {9},
	year = {2021},
	month = {2021 Sep 01},
	pages = {1175-1180},
	abstract = {PURPOSE: To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model. METHODS: Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.1\% dexamethasone ophthalmic solution (drops) for 4 weeks, tarsorrhaphy and BCL replaced weekly plus topical dexamethasone for 4 weeks, and tarsorrhaphy and DCL changed weekly for 4 weeks. Each week for 4 consecutive weeks postoperatively, the tarsorrhaphies were opened, the eyes underwent evaluation and imaging, and the tarsorrhaphies were replaced. Contact lenses were cultured on removal. Central corneal haze was assessed weekly with corneal densitometry. After 4 weeks, the animals were killed, and the eyes were enucleated for histopathologic analysis. RESULTS: The tarsorrhaphy only group displayed more haze with a greater change in optical densitometry from pre-op compared with the other treatment groups. There was no difference between the DCL group and the groups receiving a BCL and dexamethasone drops in densitometry or histopathology. No NZW rabbits developed clinical signs of infection, and cultures from DCLs and BCLs grew similar organisms. CONCLUSIONS: In the post-PRK rabbit model, DCLs worn weekly for 4 weeks were safe and as effective at preventing corneal haze as 0.1\% dexamethasone drops applied 4 times a day for 4 weeks.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002711},
	author = {Soeken, Timothy A and Ross, Amy E and Kohane, Daniel S and Kuang, Liangju and Legault, Gary L and Caldwell, Matthew C and Brundridge, Wesley L and Merkley, Michael B and Ciolino, Joseph B and Townley, J Richard}
}
@article {1817261,
	title = {Assessment of angle closure disease in the age of artificial intelligence: A review},
	journal = {Prog Retin Eye Res},
	volume = {98},
	year = {2024},
	month = {2024 Jan},
	pages = {101227},
	abstract = {Primary angle closure glaucoma is a visually debilitating disease that is under-detected worldwide. Many of the challenges in managing primary angle closure disease (PACD) are related to the lack of convenient and precise tools for clinic-based disease assessment and monitoring. Artificial intelligence (AI)- assisted tools to detect and assess PACD have proliferated in recent years with encouraging results. Machine learning (ML) algorithms that utilize clinical data have been developed to categorize angle closure eyes by disease mechanism. Other ML algorithms that utilize image data have demonstrated good performance in detecting angle closure. Nonetheless, deep learning (DL) algorithms trained directly on image data generally outperformed traditional ML algorithms in detecting PACD, were able to accurately differentiate between angle status (open, narrow, closed), and automated the measurement of quantitative parameters. However, more work is required to expand the capabilities of these AI algorithms and for deployment into real-world practice settings. This includes the need for real-world evaluation, establishing the use case for different algorithms, and evaluating the feasibility of deployment while considering other clinical, economic, social, and policy-related factors.},
	keywords = {Algorithms, Anterior Eye Segment, Artificial Intelligence, Glaucoma, Angle-Closure, Humans, Intraocular Pressure, Tomography, Optical Coherence},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2023.101227},
	author = {Soh, Zhi Da and Tan, Mingrui and Nongpiur, Monisha Esther and Xu, Benjamin Yixing and Friedman, David and Zhang, Xiulan and Leung, Christopher and Liu, Yong and Koh, Victor and Aung, Tin and Cheng, Ching-Yu}
}
@article {1589744,
	title = {The Global Extent of Undetected Glaucoma in Adults: A Systematic Review and Meta-analysis},
	journal = {Ophthalmology},
	volume = {128},
	number = {10},
	year = {2021},
	month = {2021 Oct},
	pages = {1393-1404},
	abstract = {TOPIC: Glaucoma is the leading cause of irreversible blindness, despite having good prognosis with early treatment. We evaluated the global extent of undetected glaucoma and the factors associated with it in this systematic review and meta-analysis. CLINICAL RELEVANCE: Undetected glaucoma increases the risk of vision impairment, which leads to detrimental effects on the quality-of-life and socioeconomic well-being of those affected. Detailed information on the extent and factors associated with undetected glaucoma aid in the development of public health interventions. METHODS: We conducted a systematic review and meta-analysis of population-based studies published between January 1, 1990, and June 1, 2020. Article search was conducted in online databases (PubMED, Web-of-Science), grey literatures (OpenGrey), and nongovernment organization reports. Our outcome measure was the proportion of glaucoma cases that were undetected previously. Manifest glaucoma included any form of glaucoma reported in the original studies and may include primary open-angle glaucoma (POAG), primary angle-closure-glaucoma, secondary glaucoma, or a combination thereof. Undetected glaucoma was defined as glaucoma cases that were undetected prior to diagnosis in the respective study. Random-effect meta-analysis was used to estimate the pooled proportion of undetected glaucoma. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines in our study. RESULTS: We identified 61 articles from 55 population-based studies (n\&nbsp;= 189 359 participants; n\&nbsp;= 6949 manifest glaucoma). Globally, more than half of all glaucoma cases were undetected previously on average in each geographical region. Africa (odds ratio [OR], 12.70; 95\% confidence interval [CI], 4.91-32.86) and Asia (OR, 3.41; 95\% CI, 1.63-7.16) showed higher odds of undetected glaucoma as compared with Europe. Countries with low Human Development Index (HDI; \&lt;0.55) showed a higher proportion of undetected manifest glaucoma as compared with countries of medium to very high HDI (>=0.55; all P \&lt; 0.001). In 2020, 43.78 million POAG cases were projected to be undetected, of which 76.7\% were in Africa and Asia. DISCUSSION: Undetected glaucoma is highly prevalent across diverse communities worldwide and more common in Africa and Asia. Strategies to improve detection are needed to prevent excess visual disability and blindness resulting from glaucoma.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.04.009},
	author = {Soh, Zhi and Yu, Marco and Betzler, Bjorn Kaijun and Majithia, Shivani and Thakur, Sahil and Tham, Yih Chung and Wong, Tien Yin and Aung, Tin and Friedman, David S and Cheng, Ching-Yu}
}
@article {1517177,
	title = {Corneal dystrophies},
	journal = {Nat Rev Dis Primers},
	volume = {6},
	number = {1},
	year = {2020},
	month = {2020 Jun 11},
	pages = {46},
	abstract = {Corneal dystrophies are broadly defined as inherited disorders that affect any layer of the cornea and are usually progressive, bilateral conditions that do not have systemic effects. The 2015 International Classification of Corneal Dystrophies classifies corneal dystrophies into four classes: epithelial and subepithelial dystrophies, epithelial-stromal TGFBI dystrophies, stromal dystrophies and endothelial dystrophies. Whereas some corneal dystrophies may result in few or mild symptoms and morbidity throughout a patient{\textquoteright}s lifetime, others may progress and eventually result in substantial visual and ocular disturbances that require medical or surgical intervention. Corneal transplantation, either with full-thickness or partial-thickness donor tissue, may be indicated for patients with advanced corneal dystrophies. Although corneal transplantation techniques have improved considerably over the past two decades, these surgeries are still associated with postoperative risks of disease recurrence, graft failure and other complications that may result in blindness. In addition, a global shortage of cadaveric corneal graft tissue critically limits accessibility to corneal transplantation in some parts of the world. Ongoing advances in gene therapy, regenerative therapy and cell augmentation therapy may eventually result in the development of alternative, novel treatments for corneal dystrophies, which may substantially improve the quality of life of patients with these disorders.},
	issn = {2056-676X},
	doi = {10.1038/s41572-020-0178-9},
	author = {Soh, Yu Qiang and Kocaba, Viridiana and Weiss, Jayne S and Jurkunas, Ula V and Kinoshita, Shigeru and Aldave, Anthony J and Mehta, Jodhbir S}
}
@article {1549012,
	title = {Reply},
	journal = {Retina},
	volume = {40},
	number = {11},
	year = {2020},
	month = {2020 Nov},
	pages = {e68-e69},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002958},
	author = {Sohn, Elliott H and Mullins, Robert F and Eliott, Dean}
}
@article {1528422,
	title = {Response to letter to the editor by Dhananjay Shukla},
	journal = {Retina},
	year = {2020},
	month = {2020 Aug 18},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002958},
	author = {Sohn, Elliott H and Mullins, Robert F and Eliott, Dean}
}
@article {1511474,
	title = {POSTERIORLY INSERTED VITREOUS BASE: Preoperative Characteristics, Intraoperative Findings, and Outcomes After Vitrectomy},
	journal = {Retina},
	volume = {40},
	number = {5},
	year = {2020},
	month = {2020 May},
	pages = {943-950},
	abstract = {PURPOSE: To determine the preoperative characteristics, intraoperative and postoperative complications, and outcomes of eyes with posteriorly inserted vitreous base. METHODS: In this retrospective, observational, consecutive case series at 2 academic centers, 37 patients were studied who had posteriorly inserted vitreous base noted during vitrectomy. Posteriorly inserted vitreous base was defined as the insertion of the posterior hyaloid membrane being located posterior to the vortex veins. Fifteen eyes were analyzed in a histopathologic study of donor eyes to determine the average distance of the ora serrata from the vortex veins as this distance is uncertain. RESULTS: Posteriorly inserted vitreous base was identified during vitrectomy in 31 eyes with rhegmatogenous retinal detachment (84\%), 4 with macular hole (11\%), 1 with vitreous hemorrhage, and 1 with epiretinal membrane. Adjunctive buckle was used in 24\%; 54\% had 360{\textdegree} laser. Average number of tears seen preoperatively in those with rhegmatogenous retinal detachment was 3.1. Thirty percent had new breaks identified intraoperatively. Forty-one percent had lattice degeneration; new breaks were found in 40\% of eyes with lattice. Thirteen percent of rhegmatogenous retinal detachments developed proliferative vitreoretinopathy. Average distance from the ora serrata to the vortex veins was 7.6 mm. CONCLUSION: Any eye undergoing vitrectomy may have posteriorly inserted vitreous base, but those with a high number of retinal breaks and lattice near the equator may be at highest risk. Redetachment and proliferative vitreoretinopathy still occur despite knowledge of the disorder and adjuvant treatments.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002482},
	author = {Sohn, Elliott H and Strohbehn, Austin and Stryjewski, Tomasz and Brodowska, Katarzyna and Flamme-Wiese, Miles J and Mullins, Robert F and Eliott, Dean}
}
@article {1645461,
	title = {Purtscher-like retinopathy following a bowel movement},
	journal = {Am J Ophthalmol Case Rep},
	volume = {26},
	year = {2022},
	month = {2022 Jun},
	pages = {101560},
	abstract = {Purpose: To describe a case of Purtscher-like retinopathy that developed after a bowel movement. Observations: A 32-year-old male presented with blurry vision and bilateral temporal paracentral scotomas that developed immediately after standing up from a bowel movement. Fundoscopic examination was notable for bilateral cotton wool spots in the nasal macula. Optical coherence tomography showed bilateral intraretinal fluid, subfoveal fluid, and scattered areas of inner retinal hyperreflectivity and thickening corresponding to the areas of cotton wool spots on examination. No treatment was administered and the patient had significant improvement in symptoms 2 days later with resolution of macular edema. Conclusions: Here we report a case of Purtscher-like retinopathy after a bowel movement. Although the exact mechanism of Purtscher-like retinopathy is unknown, there are multiple reports of Purtscher-like retinopathy after extreme events involving Valsalva, such as during weightlifting, and we postulate that this presentation is likely of similar pathophysiology.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101560},
	author = {Sokol, Jared T and Castillejos, Alexandra and Sobrin, Lucia}
}
@article {1761811,
	title = {REPLY: The more comorbidities present, the more likely it is Kearns-Sayre syndrome than myasthenia},
	journal = {Retin Cases Brief Rep},
	year = {2023},
	month = {2023 Sep 19},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001493},
	author = {Sokol, Jared T and Hoyek, Sandra and Patel, Nimesh A}
}
@article {1559560,
	title = {Macular Hole Closure with Medical Treatment},
	journal = {Ophthalmol Retina},
	volume = {5},
	number = {7},
	year = {2021},
	month = {2021 Jul},
	pages = {711-713},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2020.11.018},
	author = {Sokol, Jared T and Schechet, Sidney A and Komati, Rahul and Eliott, Dean and Vavvas, Demetrios G and Kaplan, Richard I and Ittiara, Shaun T and Farooq, Asim V and Sheth, Veeral S and MacCumber, Mathew W and Ke, Rhona and Gentile, Ronald C and Skondra, Dimitra}
}
@article {1538346,
	title = {WDR34, a candidate gene for non-syndromic rod-cone dystrophy},
	journal = {Clin Genet},
	volume = {99},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {298-302},
	abstract = {Rod-cone dystrophy (RCD), also called retinitis pigmentosa, is characterized by rod followed by cone photoreceptor degeneration, leading to gradual visual loss. Mutations in over 65 genes have been associated with non-syndromic RCD explaining 60\% to 70\% of cases, with novel gene defects possibly accounting for the unsolved cases. Homozygosity mapping and whole-exome sequencing applied to a case of autosomal recessive non-syndromic RCD from a consanguineous union identified a homozygous variant in WDR34. Mutations in WDR34 have been previously associated with severe ciliopathy syndromes possibly associated with a retinal dystrophy. This is the first report of a homozygous mutation in WDR34 associated with non-syndromic RCD.},
	issn = {1399-0004},
	doi = {10.1111/cge.13872},
	author = {Solaguren-Beascoa, Maria and Bujakowska, Kinga M and M{\'e}j{\'e}case, C{\'e}cile and Emmenegger, Lisa and Orhan, Elise and Neuill{\'e}, Marion and Mohand-Sa{\"\i}d, Saddek and Condroyer, Christel and Lancelot, Marie-Elise and Michiels, Christelle and Demontant, Vanessa and Antonio, Aline and Letexier, M{\'e}lanie and Saraiva, Jean-Paul and Lonjou, Christine and Carpentier, Wassila and L{\'e}veillard, Thierry and Pierce, Eric A and Dollfus, H{\'e}l{\`e}ne and Sahel, Jos{\'e}-Alain and Bhattacharya, Shomi S and Audo, Isabelle and Zeitz, Christina}
}
@article {1732691,
	title = {Application of biomaterials and nanotechnology in corneal tissue engineering},
	journal = {J Int Med Res},
	volume = {51},
	number = {7},
	year = {2023},
	month = {2023 Jul},
	pages = {3000605231190473},
	abstract = {Corneal diseases are among the most common causes of blindness worldwide. Regardless of the etiology, corneal opacity- or globe integrity-threatening conditions may necessitate corneal replacement procedures. Several procedure types are currently available to address these issues, based on the complexity and extent of injury. Corneal allograft or keratoplasty is considered to be first-line treatment in many cases. However, a significant proportion of the world{\textquoteright}s population are reported to have no access to this option due to limitations in donor preparation. Thus, providing an appropriate, safe, and efficient synthetic implant (e.g., artificial cornea) may revolutionize this field. Nanotechnology, with its potential applications, has garnered a lot of recent attention in this area, however, there is seemingly a long way to go. This narrative review provides a brief overview of the therapeutic interventions for corneal pathologies, followed by a summary of current biomaterials used in corneal regeneration and a discussion of the nanotechnologies that can aid in the production of superior implants.},
	keywords = {Biocompatible Materials, Cornea, Corneal Diseases, Humans, Nanotechnology, Tissue Engineering},
	issn = {1473-2300},
	doi = {10.1177/03000605231190473},
	author = {Soleimani, Mohammad and Ebrahimi, Zohreh and Ebrahimi, Kosar Sadat and Farhadian, Negin and Shahlaei, Mohsen and Cheraqpour, Kasra and Ghasemi, Hamed and Moradi, Sajad and Chang, Arthur Y and Sharifi, Sina and Baharnoori, Seyed Mahbod and Djalilian, Ali R}
}
@article {1658683,
	title = {Archetypal analysis of visual fields in optic neuritis reveals functional biomarkers associated with outcome and treatment response},
	journal = {Mult Scler Relat Disord},
	volume = {67},
	year = {2022},
	month = {2022 Nov},
	pages = {104074},
	abstract = {BACKGROUND AND OBJECTIVES: Archetypal analysis (AA), a form of unsupervised machine learning, can identify quantifiable visual field (VF) patterns seen in optic neuritis (ON), known as archetypes (ATs). We hypothesized that AT weight changes over time would reflect the course of recovery and the effects of therapy in ON. We explored whether baseline AT weights would be associated with VF status at the clinical trial outcome and if ATs would indicate residual VF defects in eyes with mean deviation (MD) >= -2.00 at six months. METHODS: We used a published 16-AT model derived from 3892 Optic Neuritis Treatment Trial VFs (456 eyes) for all analyses. We measured AT weight changes over the six-month study period and used asymptotic regression to analyze the rate of change. We compared AT weights at six months between treatment groups. We evaluated associations between baseline AT weight thresholds and VF outcome or treatment effect. We calculated residual AT weights in eyes with MD >= -2.00\&nbsp;dB at six months. RESULTS: Over six months, AT1 (a normal VF pattern) demonstrated the greatest median weight change, increasing from 0.00\% (IQR 0.00-0.00\%) at baseline to 60.0\% (IQR 38.3-70.8\%) at six months (p\&nbsp;\&lt;\&nbsp;0.001). At outcome, the intravenous methylprednisolone (IVMP) group had the highest median AT1 weight (IVMP: 63.3\%, IQR 51.3-72.8\%; placebo: 56.2\%, IQR 35.1-71.6\%; prednisone 58.3\%, IQR 35.1-71.6\%; p\&nbsp;=\&nbsp;0.019). Eyes with AT1 weight >= 19\% at baseline had superior median MD values (-0.91 vs. -2.07\&nbsp;dB, p\&nbsp;\&lt;\&nbsp;0.001) and AT1 weights (70.8\% vs. 57.8\% p\&nbsp;\&lt;\&nbsp;0.001) at six months. Only eyes with AT1 weight \&lt; 19\% at baseline showed a treatment benefit for IVMP, with a higher six-month median AT1 weight compared to placebo (p\&nbsp;=\&nbsp;0.015) and prednisone (p\&nbsp;=\&nbsp;0.016), and a higher median MD compared to placebo (p\&nbsp;=\&nbsp;0.027). At six months, 182 (80.2\%) VFs with MD >= -2.00 had at least one abnormal AT. DISCUSSION: Changes in quantifiable, archetypal patterns of VF loss reflect recovery in ON. Machine learning analysis of the VFs in optic neuritis reveals associations with response to therapy and VF outcome, and uncovers residual deficits, not readily seen with standard evaluations.},
	keywords = {Biomarkers, Disease Progression, Humans, Methylprednisolone, Optic Neuritis, Prednisone, Retrospective Studies, Vision Disorders, Visual Fields},
	issn = {2211-0356},
	doi = {10.1016/j.msard.2022.104074},
	author = {Solli, Elena and Doshi, Hiten and Tobias Elze and Pasquale, Louis R and Branco, Joseph and Wall, Michael and Kupersmith, Mark}
}
@article {1629460,
	title = {Archetypal Analysis Reveals Quantifiable Patterns of Visual Field Loss in Optic Neuritis},
	journal = {Transl Vis Sci Technol},
	volume = {11},
	number = {1},
	year = {2022},
	month = {2022 01 03},
	pages = {27},
	abstract = {Purpose: Identifying and monitoring visual field (VF) defects due to optic neuritis (ON) relies on qualitative clinician interpretation. Archetypal analysis (AA), a form of unsupervised machine learning, is used to quantify VF defects in glaucoma. We hypothesized that AA can identify quantifiable, ON-specific patterns (as archetypes [ATs]) of VF loss that resemble known ON VF defects. Methods: We applied AA to a dataset of 3892 VFs prospectively collected from 456 eyes in the Optic Neuritis Treatment Trial (ONTT), and decomposed each VF into component ATs (total weight = 100\%). AA of 568 VFs from 61 control eyes was used to define a minimum meaningful (<=7\%) AT weight and weight change. We correlated baseline ON AT weights with global VF indices, visual acuity, and contrast sensitivity. For eyes with a dominant AT (weight >=50\%), we compared the ONTT VF classification with the AT pattern. Results: AA generated a set of 16 ATs containing patterns seen in the ONTT. These were distinct from control ATs. Baseline study eye VFs were decomposed into 2.9 {\textpm} 1.5 ATs. AT2, a global dysfunction pattern, had the highest mean weight at baseline (36\%; 95\% confidence interval, 33\%-40\%), and showed the strongest correlation with MD (r = -0.91; P \&lt; 0.001), visual acuity (r = 0.70; P \&lt; 0.001), and contrast sensitivity (r = -0.77; P \&lt; 0.001). Of 191 baseline VFs with a dominant AT, 81\% matched the descriptive classifications. Conclusions: AA identifies and quantifies archetypal, ON-specific patterns of VF loss. Translational Relevance: AA is a quantitative, objective method for demonstrating and monitoring change in regional VF deficits in ON.},
	keywords = {Humans, Optic Neuritis, Retrospective Studies, Vision Disorders, Visual Field Tests, Visual Fields},
	issn = {2164-2591},
	doi = {10.1167/tvst.11.1.27},
	author = {Solli, Elena and Doshi, Hiten and Tobias Elze and Pasquale, Louis and Wall, Michael and Kupersmith, Mark}
}
@article {1043276,
	title = {Diabetic Retinopathy: A Position Statement by the American Diabetes Association},
	journal = {Diabetes Care},
	volume = {40},
	number = {3},
	year = {2017},
	month = {2017 Mar},
	pages = {412-418},
	issn = {1935-5548},
	doi = {10.2337/dc16-2641},
	author = {Solomon, Sharon D and Chew, Emily and Duh, Elia J and Sobrin, Lucia and Sun, Jennifer K and VanderBeek, Brian L and Wykoff, Charles C and Gardner, Thomas W}
}
@article {1608583,
	title = {Juvenile ossifying fibroma of the maxilla presenting with proptosis and dystopia in a 4-year-old child},
	journal = {Orbit},
	volume = {40},
	number = {4},
	year = {2021},
	month = {2021 Aug},
	pages = {347-349},
	issn = {1744-5108},
	doi = {10.1080/01676830.2020.1778739},
	author = {Solyman, Omar and Zaakouk, Mohamed and Elhusseiny, Abdelrahman M}
}
@article {1762031,
	title = {The use of the built-in macro mode of smartphone cameras for pediatric external and anterior segment digital photography},
	journal = {J AAPOS},
	year = {2023},
	month = {2023 Sep 13},
	abstract = {We describe a novel method for clinical ophthalmic photography that uses the inherent macro-photography mode available in most recent smartphones, without additional attachments. This method facilitates acquisition of high-quality external and anterior segment clinical photography in children who may have difficulty remaining still enough for anterior segment photography at the slit lamp. We describe this technique and discuss its advantages and limitations.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2023.07.004},
	author = {Solyman, Omar and Elhusseiny, Abdelrahman M and Galal, Sameh}
}
@article {1522739,
	title = {Severe bilateral ankyloblepharon filiforme adnatum},
	journal = {J AAPOS},
	year = {2020},
	month = {2020 Jul 01},
	abstract = {We present a case of bilateral ankyloblepharon filiforme adnatum in 1-day-old girl and describe our surgical approach. The bands connecting the upper and lower eyelids of both eyes were severed using blunt scissors. Point bleeding at the cut bands stopped in 1-2 minutes, without the need for cauterization or compression. The patient was able to open her eyes shortly after the procedure, as she woke up from anesthesia. Examination under general anesthesia showed normal eye examination appropriate for age. Postoperatively, the patient maintained open palpebral fissures. Visual development over 3 years{\textquoteright} follow-up was normal.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2020.04.002},
	author = {Solyman, Omar and Elhusseiny, Abdelrahman M and Hashem, Hisham A}
}
@article {1732646,
	title = {The Use of Additional Facedown Positioning with Silicone Oil Tamponade for the Treatment of Retinal Re-detachment},
	journal = {Retin Cases Brief Rep},
	year = {2023},
	month = {2023 Jul 19},
	abstract = {PURPOSE: To highlight a potential alternative to additional surgery for management of retinal re-detachment through the use of additional facedown positioning with silicone oil tamponade. METHODS: Retrospective case-series of two patients evaluated with examination, multimodal imaging, including fundus photography, optical coherence tomography (OCT), and fluorescein angiography. RESULTS: In case 1, a 70-year-old female patient underwent surgery for a full-thickness macular hole with associated macula-off retinal detachment, but experienced a recurrent detachment and underwent a second surgery with silicone oil placement. Another recurrent detachment was found. The case was managed conservatively with face-down positioning, resulting in resolution of subretinal fluid and improvement in vision. At follow-up, the retina remained attached with stable vision. In case 2, a 25-year-old male patient underwent a surgical repair for PVR retinal detachment with a scleral buckle, cryotherapy, and external drainage. After multiple re-detachment surgeries with retinectomy and oil placement there was another tractional re-detachment of the fovea was noted. Management was with facedown positioning and follow-up evaluation showed resolution of the subretinal fluid and improvement in vision with stability for greater than 2 months. CONCLUSIONS: For recurrent retinal re-detachments with silicone oil in place, an additional week of facedown positioning can result in anatomic success and be a viable alternative or bridge to invasive surgical interventions. This approach may have greatest utility for patients who are poor surgical candidates without new peripheral pathology.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001461},
	author = {Somisetty, Aditya and Hoyek, Sandra and Yuan, Melissa and Somisetty, Swathi and Kim, Leo A and Patel, Nimesh A}
}
@article {1445335,
	title = {Rapid onset of orbital cellulitis after uncomplicated strabismus surgery},
	journal = {J AAPOS},
	year = {2019},
	month = {2019 Jun 08},
	abstract = {Orbital cellulitis is extremely uncommon following strabismus surgery. When it occurs, the infection has been reported to present from day 1 to within 1 week following surgery and has the potential for significant morbidity postoperatively. We report the case of a 6-year-old boy presenting with unilateral orbital cellulitis growing group A Streptococcus pyogenes on postoperative day 1, after uncomplicated bilateral medial rectus recessions. The patient had two contacts with streptococcal pharyngitis at the time of surgery but was completely asymptomatic himself. We hypothesize that these contacts may have led to the rapid onset of his orbital cellulitis.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.05.006},
	author = {Somsen, David and Heidary, Gena}
}
@article {1642025,
	title = {Nocturnal normobaric hyperoxia treatment in a case of chronic diabetic macular edema},
	journal = {Eur J Ophthalmol},
	year = {2022},
	month = {2022 May 20},
	pages = {11206721221101365},
	abstract = {PURPOSE: To study the long-term anatomic and physiologic effects of nocturnal normobaric hyperoxia (NNBH) in a patient with treatment-resistant diabetic macular edema (DME). METHODS: A 64-year-old diabetic man with bilateral DME requiring regular anti-VEGF treatments in both eyes was started on 5 LPM (40\% FiO2) NNBH treatment 6-h per night. Visual acuity, OCT measurements of retinal thickness and volume, as well as the number of injections given in each eye were retrospectively examined one year prior and prospectively after initiation of NNBH, as well as before and after a planned 1-month discontinuation of NNBH. RESULTS: The patient received 12 anti-VEGF injections in the year prior to beginning NNBH treatment (4 OD; 8 OS) and did not require any injections after commencing NNBH treatment. Visual acuity improved and stabilized to 20/20 and macular edema rapidly resolved in both eyes following initiation of NNBH. After a planned 1-month NNBH vacation, DME recurred but quickly resolved once NNBH treatment was restarted. CONCLUSION: This model case demonstrates that a 6-h NNBH regimen can be successful in treating DME and improving vision, without the need for intravitreal injections. NNBH is a more acceptable treatment regimen compared to 24-h continuous oxygen delivery and may provide a less invasive alternate method for treating DME in patients with diabetes. Further study is warranted.},
	issn = {1724-6016},
	doi = {10.1177/11206721221101365},
	author = {Song, Soobin and Lemire, Colin A and Seto, Brendan and Arroyo, Jorge G}
}
@article {1709816,
	title = {Gut microbial fatty acid isomerization modulates intraepithelial T cells},
	journal = {Nature},
	volume = {619},
	number = {7971},
	year = {2023},
	month = {2023 Jul},
	pages = {837-843},
	abstract = {The human gut microbiome constantly converts natural products derived from the host and diet into numerous bioactive metabolites1-3. Dietary fats are essential micronutrients that undergo lipolysis to release free fatty acids (FAs) for absorption in the small intestine4. Gut commensal bacteria modify some unsaturated FAs-for example, linoleic acid (LA)-into various intestinal FA isomers that regulate host metabolism and have anticarcinogenic properties5. However, little is known about how this diet-microorganism FA isomerization network affects the mucosal immune system of the host. Here we report that both dietary factors\&nbsp;and microbial factors influence the level of gut LA isomers (conjugated LAs (CLAs)) and that CLAs in turn modulate a distinct population of CD4+ intraepithelial lymphocytes (IELs) that express CD8αα in the small intestine. Genetic abolition of FA isomerization pathways in individual gut symbionts significantly decreases the number of CD4+CD8αα+ IELs in gnotobiotic mice. Restoration of CLAs increases CD4+CD8αα+ IEL levels in the presence of the transcription factor hepatocyte nuclear factor 4γ (HNF4γ). Mechanistically, HNF4γ facilitates CD4+CD8αα+ IEL development by modulating interleukin-18 signalling. In mice, specific deletion of HNF4γ in T cells leads to early mortality from infection by intestinal pathogens. Our data reveal a new role for bacterial FA metabolic pathways in the control of host intraepithelial immunological homeostasis by modulating the relative number of CD4+ T cells that were CD4+CD8αα+.},
	keywords = {Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Fatty Acids, Gastrointestinal Microbiome, Humans, Immunity, Mucosal, Intestinal Mucosa, Intraepithelial Lymphocytes, Isomerism, Linoleic Acid, Lipolysis, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, alpha-beta},
	issn = {1476-4687},
	doi = {10.1038/s41586-023-06265-4},
	author = {Song, Xinyang and Zhang, Haohao and Zhang, Yanbo and Goh, Byoungsook and Bao, Bin and Mello, Suelen S and Sun, Ximei and Zheng, Wen and Gazzaniga, Francesca S and Wu, Meng and Qu, Fangfang and Yin, Qiangzong and Gilmore, Michael S and Oh, Sungwhan F and Kasper, Dennis L}
}
@article {1328903,
	title = {Assessment of surgeon experience with femtosecond laser-assisted cataract surgery},
	journal = {Clin Ophthalmol},
	volume = {12},
	year = {2018},
	month = {2018},
	pages = {1373-1377},
	abstract = {Purpose: To evaluate the collective user experience with an image-guided femtosecond laser (FSL) for cataract surgery in a high-volume, multi-surgeon, ambulatory surgical center. Subjects and methods: A detailed online survey was distributed to all surgeons in a single ambulatory surgical center who had performed cataract surgery using a FSL since its acquisition in December 2012. Information collected included the number of cases performed, typical surgical techniques and parameters, satisfaction with individual features of the laser (rated on a scale from 1=completely unsatisfied to 10=extremely satisfied) and commentary on ease of use and suggested improvements. Results: Seventeen of 30 surgeons (56.7\%) completed the survey, representing a case volume of 1,967 eyes. Fourteen surgeons (82.4\%) felt they required <=10 cases with the FSL to operate with the same safety and control as in standard phacoemulsification surgery. Satisfaction was highest for capsulotomies, lens fragmentation, lens softening, arcuate incisions and the graphic user interface (mean scores 9.4, 8.7, 8.7, 7.2 and 8.9, respectively). Preferred capsulotomy diameter was 4.8-5.2 mm (64.7\% of respondents). About half (52.9\%) of respondents centered the capsulotomy on the pupil and the other 47.1\% centered the capsulotomy using optical coherence tomography. Most respondents (81.3\%) preferred transepithelial arcuate incisions compared to intrastromal incisions. Satisfaction was lowest with FSL-created, main, clear corneal incisions and paracenteses (mean scores 4.4 and 4.2, respectively). Conclusion: Laser-assisted cataract surgery has a short learning curve and a high rate of user satisfaction. Further software and hardware development is warranted to improve user satisfaction with peripheral and clear corneal incisions.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S171743},
	author = {Song, Christian and Baharozian, Connor J and Hatch, Kathryn M and Talamo, Jonathan H}
}
@article {959481,
	title = {Presence and Risk Factors for Glaucoma in Patients with Diabetes.},
	journal = {Curr Diab Rep},
	volume = {16},
	number = {12},
	year = {2016},
	month = {2016 Dec},
	pages = {124},
	abstract = {Diabetes mellitus represents a growing international public health issue with a near quadrupling in its worldwide prevalence since 1980. Though it has many known microvascular complications, vision loss from diabetic retinopathy is one of the most devastating for affected individuals. In addition, there is increasing evidence to suggest that diabetic patients have a greater risk for glaucoma as well. Though the pathophysiology of glaucoma is not completely understood, both diabetes and glaucoma appear to share some common risk factors and pathophysiologic similarities with studies also reporting that the presence of diabetes and elevated fasting glucose levels are associated with elevated intraocular pressure-the primary risk factor for glaucomatous optic neuropathy. While no study has completely addressed the possibility of detection bias, most recent epidemiologic evidence suggests that diabetic populations are likely enriched with glaucoma patients. As the association between diabetes and glaucoma becomes better defined, routine evaluation for glaucoma in diabetic patients, particularly in the telemedicine setting, may become a reasonable consideration to reduce the risk of vision loss in these patients.},
	issn = {1539-0829},
	doi = {10.1007/s11892-016-0815-6},
	author = {Song, Brian J and Aiello, Lloyd Paul and Pasquale, Louis R}
}
@article {303941,
	title = {A murine RP1 missense mutation causes protein mislocalization and slowly progressive photoreceptor degeneration},
	journal = {Am J Pathol},
	volume = {184},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {2721-9},
	abstract = {Mutations in the RP1 gene can cause retinitis pigmentosa. We identified a spontaneous L66P mutation caused by two adjacent point mutations in the Rp1 gene in a colony of C57BL/6J mice. Mice homozygous for the L66P mutation exhibited slow, progressive photoreceptor degeneration throughout their lifespan. Optical coherence tomography imaging found abnormal photoreceptor reflectivity at 1 month of age. Histology found shortening and disorganization of the photoreceptor inner and outer segments and progressive thinning of the outer nuclear layer. Electroretinogram a- and b-wave amplitudes were decreased with age. Western blot analysis found that the quantity and size of the mutated retinitis pigmentosa 1 (RP1) protein were normal. However, immunohistochemistry found that the mutant Rp1 protein partially mislocalized to the transition zone of the shortened axonemes. This mutation disrupted colocalization with cytoplasmic microtubules in\&nbsp;vitro. In conclusion, the L66P mutation in the first doublecortin domain of the Rp1 gene impairs Rp1 protein localization and function, leading to abnormalities in photoreceptor outer segment structure and progressive photoreceptor degeneration. This is the first missense mutation in Rp1 shown to cause retinal degeneration. It provides a unique, slowly progressive photoreceptor degeneration model that mirrors the slow degeneration kinetics in most patients with retinitis pigmentosa.},
	keywords = {Animals, Axoneme, Cercopithecus aethiops, COS Cells, Electroretinography, Eye Proteins, Female, Homozygote, Humans, Male, Mice, Mice, Inbred C57BL, Microtubule-Associated Proteins, Mutation, Missense, Photoreceptor Cells, Retinal Degeneration},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2014.06.010},
	author = {Song, Delu and Grieco, Steve and Li, Yafeng and Hunter, Allan and Chu, Sally and Zhao, Liangliang and Song, Ying and DeAngelis, Robert A and Shi, Lan-Ying and Liu, Qin and Pierce, Eric A and Nishina, Patsy M and Lambris, John D and Dunaief, Joshua L}
}
@article {1603845,
	title = {Post-keratoplasty Infectious Keratitis: Epidemiology, Risk Factors, Management, and Outcomes},
	journal = {Front Med (Lausanne)},
	volume = {8},
	year = {2021},
	month = {2021},
	pages = {707242},
	abstract = {Post-keratoplasty infectious keratitis (PKIK) represents a unique clinical entity that often poses significant diagnostic and therapeutic challenges. It carries a high risk of serious complications such as graft rejection and failure, and less commonly endophthalmitis. Topical corticosteroids are often required to reduce the risk of graft rejection but their use in PKIK may act as a double-edged sword, particularly in fungal infection. The increased uptake in lamellar keratoplasty in the recent years has also led to complications such as graft-host interface infectious keratitis (IIK), which is particularly difficult to manage. The reported incidence of PKIK differs considerably across different countries, with a higher incidence observed in developing countries (9.2-11.9\%) than developed countries (0.02-7.9\%). Common risk factors for PKIK include the use of topical corticosteroids, suture-related problems, ocular surface diseases and previous corneal infection. PKIK after penetrating keratoplasty or (deep) anterior lamellar keratoplasty is most commonly caused by ocular surface commensals, particularly Gramme-positive bacteria, whereas PKIK after endothelial keratoplasty is usually caused by Candida spp. Empirical broad-spectrum antimicrobial treatment is the mainstay of treatment for both PKIK, though surgical interventions are required in medically refractory cases (during the acute phase) and those affected by visually significant scarring (during the late phase). In this paper, we aim to provide a comprehensive overview on PKIK, encompassing the epidemiology, risk factors, causes, management and outcomes, and to propose a treatment algorithm for systematically managing this challenging condition.},
	issn = {2296-858X},
	doi = {10.3389/fmed.2021.707242},
	author = {Song, Anna and Deshmukh, Rashmi and Lin, Haotian and Ang, Marcus and Mehta, Jodhbir S and Chodosh, James and Said, Dalia G and Dua, Harminder S and Ting, Darren S J}
}
@article {836971,
	title = {Trabeculectomy and Combined Phacoemulsification-Trabeculectomy: Outcomes and Risk Factors for Failure in Primary Angle Closure Glaucoma.},
	journal = {J Glaucoma},
	volume = {25},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {763-9},
	abstract = {PURPOSE: To evaluate tonometric outcomes of patients with primary angle closure glaucoma (PACG) who have undergone trabeculectomy with mitomycin C (MMC) with and without concurrent phacoemulsification and to identify risk factors for postoperative failure. PATIENTS AND METHODS: Retrospective cohort study of 44 eyes of 33 phakic patients who underwent trabeculectomy with MMC with or without combined phacoemulsification for PACG. The primary endpoint was qualified tonometric success at 12 months according to predefined criteria. LogMAR visual acuity, number of glaucoma medications, and postoperative complications were also evaluated. Cox proportional hazard regression analysis was performed to identify potential risk factors for trabeculectomy failure. RESULTS: Mean intraocular pressure (IOP) decreased from 21.3{\textpm}7.9 to 12.2{\textpm}3.9 mm Hg at 12 months (P\&lt;0.001) in all patients. A significant reduction in mean number of glaucoma medications (P\&lt;0.001) was also seen. There was no change in logMAR visual acuity (P=0.39) after 12 months. There were no significant intergroup differences in mean IOP (P=0.42), number of glaucoma medications (P=0.85), or logMAR visual acuity (P=0.42) between the trabeculectomy versus combined surgery groups after 12 months. Increased age, greater baseline IOP, limbus-based conjunctival flaps, and MMC duration \&gt;1 minute were associated with decreased risk of surgical failure. Concurrent phacoemulsification at the time of trabeculectomy did not alter tonometric success or rate of complications. CONCLUSIONS: In phakic patients with PACG, trabeculectomy with MMC significantly reduces IOP and number of glaucoma medications at 12 months without change in visual acuity. However, success rates are modest when based on more demanding tonometric criteria.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000493},
	author = {Song, Brian J and Ramanathan, Meera and Morales, Esteban and Law, Simon K and Giaconi, JoAnn A and Coleman, Anne L and Caprioli, Joseph}
}
@article {1233371,
	title = {Combined Intravitreal and Systemic Antibiotic Therapy in a Patient with Syphilitic Uveitis},
	journal = {Ocul Immunol Inflamm},
	year = {2017},
	month = {2017 Oct 20},
	pages = {1-3},
	abstract = {PURPOSE: To report the novel use of combined intravitreal and systemic antibiotic therapy in a patient with syphilitic panuveitis and discuss the management of ocular syphilis. METHODS: Case report Results: A 45-year old heterosexual male with human immunodeficiency virus (HIV) presented with 1\&nbsp;month of blurry vision in both eyes. Clinical examination revealed a bilateral panuveitis. The patient denied history of genital lesions or rash, but did complain of difficulty hearing bilaterally. Treponemal EIA was positive, the RPR titer greater than 1:512 dilution, and CSF VDRL 1:4. A diagnosis of neurosyphilis and ocular syphilis was made based on the clinical and laboratory findings. The patient was admitted for systemic intravenous antibiotic therapy, but was noted to have a penicillin allergy. Intravitreal ceftazidime was promptly administered bilaterally to achieve treponemacidal levels of antibiotic therapy. After penicillin desensitization protocol, the patient received 14\&nbsp;days of intravenous penicillin with clinical resolution. CONCLUSIONS: There are increasing reports of ocular syphilis in the United States and delay in diagnosis and management can lead to severe visual impairment and blindness. We report the first case of adjunct intravitreal antibiotic therapy in a penicillin allergic patient. As ocular syphilis is a form of bacterial endophthalmitis, combination intravitreal and systemic antibiotics may be considered.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2017.1385817},
	author = {Sood, Arjun B and Pearce, William A and Workowski, Kimberly A and Lockwood, James and Yeh, Steven}
}
@article {1319482,
	title = {Vogt-Koyanagi-Harada Disease Associated with Hepatitis B Vaccination},
	journal = {Ocul Immunol Inflamm},
	year = {2018},
	month = {2018 Jun 28},
	pages = {1-4},
	abstract = {PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) disease associated with hepatitis B vaccination. METHODS: Case report. RESULTS: A 43-year-old Caucasian male presented with a three-week history of blurry vision, pain, photophobia, and redness in both eyes. Three days prior to the onset of symptoms, he had received the hepatitis B virus vaccine. Clinical evaluation revealed multifocal placoid lesions in the posterior pole, choroidal thickening, and serous macular detachment. Targeted laboratory investigations were negative for infectious or autoimmune markers. After treatment with oral corticosteroids, the patient had resolution of symptoms with near-total recovery of visual function. The patient later reported systemic findings of hearing loss, tinnitus, and integumentary changes. A diagnosis of VKH disease was made and inflammation was managed with oral corticosteroids followed by methotrexate for long-term disease control. CONCLUSIONS: VKH disease is an inflammatory condition primarily affecting the choroid, retinal pigment epithelium, and outer retina. The underlying etiology is unclear, but it can be associated with a viral prodrome suggesting an infectious trigger in a genetically susceptible individual. Our case suggests that hepatitis B vaccination may trigger a similar inflammatory response.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2018.1483520},
	author = {Sood, Arjun B and O{\textquoteright}Keefe, Ghazala and Bui, Diem and Jain, Nieraj}
}
@article {1782386,
	title = {Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering},
	journal = {Proc Natl Acad Sci U S A},
	volume = {120},
	number = {46},
	year = {2023},
	month = {2023 Nov 14},
	pages = {e2302089120},
	abstract = {Ongoing cell therapy trials have demonstrated the need for precision control of donor cell behavior within the recipient tissue. We present a methodology to guide stem cell-derived and endogenously regenerated neurons by engineering the microenvironment. Being an "approachable part of the brain," the eye provides a unique opportunity to study neuron fate and function within the central nervous system. Here, we focused on retinal ganglion cells (RGCs)-the neurons in the retina are irreversibly lost in glaucoma and other optic neuropathies but can potentially be replaced through transplantation or reprogramming. One of the significant barriers to successful RGC integration into the existing mature retinal circuitry is cell migration toward their natural position in the retina. Our in silico analysis of the single-cell transcriptome of the developing human retina identified six receptor-ligand candidates, which were tested in functional in vitro assays for their ability to guide human stem cell-derived RGCs. We used our lead molecule, SDF1, to engineer an artificial gradient in the retina, which led to a 2.7-fold increase in donor RGC migration into the ganglion cell layer (GCL) and a 3.3-fold increase in the displacement of newborn RGCs out of the inner nuclear layer. Only donor RGCs that migrated into the GCL were found to express mature RGC markers, indicating the importance of proper structure integration. Together, these results describe an "in silico-in vitro-in vivo" framework for identifying, selecting, and applying soluble ligands to control donor cell function after transplantation.},
	keywords = {Cell Movement, Humans, Infant, Newborn, neurogenesis, Retina, Retinal Ganglion Cells, Stem Cells},
	issn = {1091-6490},
	doi = {10.1073/pnas.2302089120},
	author = {Soucy, Jonathan R and Todd, Levi and Kriukov, Emil and Phay, Monichan and Malechka, Volha V and Rivera, John Dayron and Reh, Thomas A and Baranov, Petr}
}
@article {1761776,
	title = {Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium},
	journal = {Mol Neurodegener},
	volume = {18},
	number = {1},
	year = {2023},
	month = {2023 Sep 21},
	pages = {64},
	abstract = {Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system{\textquoteright}s limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology \&amp; immunotolerance, neuropathology \&amp; neuroprotection, materials science \&amp; biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium{\textquoteright}s efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.},
	keywords = {Animals, Brain, Cell Differentiation, Humans, Mammals, Optic Nerve Diseases, Retina, Retinal Ganglion Cells},
	issn = {1750-1326},
	doi = {10.1186/s13024-023-00655-y},
	author = {Soucy, Jonathan R and Aguzzi, Erika A and Cho, Julie and Gilhooley, Michael James and Keuthan, Casey and Luo, Ziming and Monavarfeshani, Aboozar and Saleem, Meher A and Wang, Xue-Wei and Wohlschlegel, Juilette and RReSTORe Consortium and Baranov, Petr and Di Polo, Adriana and Fortune, Brad and Gokoffski, Kimberly K and Goldberg, Jeffrey L and Guido, William and Kolodkin, Alex L and Mason, Carol A and Ou, Yvonne and Reh, Thomas A and Ross, Ahmara G and Samuels, Brian C and Welsbie, Derek and Zack, Donald J and Johnson, Thomas V}
}
@article {1732616,
	title = {COMPLEMENT INHIBITION FOR GEOGRAPHIC ATROPHY: Review of Salient Functional Outcomes and Perspective},
	journal = {Retina},
	volume = {43},
	number = {7},
	year = {2023},
	month = {2023 Jul 01},
	pages = {1064-1069},
	abstract = {PURPOSE: To evaluate available rationale and outcomes of randomized trial results for complement inhibition for geographic atrophy. METHODS: Data from recently completed randomized trials of complement inhibition, particularly for pegcetacoplan and avacincaptad pegol, were evaluated for both the outcome, area of autofluorescence loss, and functional vision tests. RESULTS: Pegcetacoplan 2 mg showed statistically significant reduction in expansion of the area of autofluorescence loss with monthly, but not every-other-month dosing, in a 12-month phase two trial. Nearly 40\% of patients recruited for the monthly arm did not complete the treatment. In two parallel phase 3 studies there was a statistically significant reduction in the area of atrophy in one but not both studies as compared with untreated controls. Data released at 24 months follow-up showed statistically significant reduction in the area of autofluorescence-detected atrophy in both studies compared with sham. Patients did not show functional difference in best-corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and mean microperimetry threshold sensitivities in the treatment versus sham arms. Avacincaptad pegol was evaluated in two randomized pivotal studies and showed a statistically significant reduction in the expansion of autofluorescence loss at 12 months. Patients in the treatment arms did not show any difference as compared with sham in the best-corrected visual acuity or low luminance visual acuity, the only functional outcomes mentioned. Both drugs increased the risk of macular neovascularization. CONCLUSION: Both avacincaptad pegol and pegcetacoplan show significant differences compared with sham in autofluorescence imaging but no benefit in visual function at 12 and 24 months, respectively.},
	keywords = {Atrophy, Geographic Atrophy, Humans, Macular Degeneration, Visual Acuity},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003796},
	author = {Spaide, Richard F and Vavvas, Demetrios G}
}
@article {603836,
	title = {Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina.},
	journal = {Adv Exp Med Biol},
	volume = {854},
	year = {2016},
	month = {2016},
	pages = {285-90},
	abstract = {Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina.},
	issn = {0065-2598},
	doi = {10.1007/978-3-319-17121-0_38},
	author = {Sparrow, Janet R and Duncker, Tobias and Woods, Russell and Delori, Fran{\c c}ois C}
}
@article {1059821,
	title = {Identification of a synergistic interaction between endothelial cells and retinal pigment epithelium},
	journal = {J Cell Mol Med},
	volume = {21},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {2542-2552},
	abstract = {The retinal pigment epithelium located between the neurosensory retina and the choroidal vasculature is critical for the function and maintenance of both the photoreceptors and underlying capillary endothelium. While the trophic role of retinal pigment epithelium on choroidal endothelial cells is well recognized, the existence of a reciprocal regulatory function of endothelial cells on retinal pigment epithelium cells remained to be fully characterized. Using a physiological long-term co-culture system, we determined the effect of retinal pigment epithelium-endothelial cell heterotypic interactions on cell survival, behaviour and matrix deposition. Human retinal pigment epithelium and endothelial cells were cultured on opposite sides of polyester transwells for up to 4\&nbsp;weeks in low serum conditions. Cell viability was quantified using a trypan blue assay. Cellular morphology was evaluated by H\&amp;E staining, S.E.M. and immunohistochemistry. Retinal pigment epithelium phagocytic function was examined using a fluorescent bead assay. Gene expression analysis was performed on both retinal pigment epithelium and endothelial cells by quantitative PCR. Quantification of extracellular matrix deposition was performed on decellularized transwells stained for collagen IV, fibronectin and fibrillin. Our results showed that presence of endothelial cells significantly improves retinal pigment epithelium maturation and function as indicated by the induction of visual cycle-associated genes, accumulation of a Bruch{\textquoteright}s membrane-like matrix and increase in retinal pigment epithelium phagocytic activity. Co-culture conditions led to increased expression of anti-angiogenic growth factors and receptors in both retinal pigment epithelium and endothelial cells compared to monoculture. Tube-formation assays confirmed that co-culture with retinal pigment epithelium significantly decreased the angiogenic phenotype of endothelial cells. These findings provide evidence of critical interdependent interactions between retinal pigment epithelium and endothelial cell involved in the maintenance of retinal homeostasis.},
	issn = {1582-4934},
	doi = {10.1111/jcmm.13175},
	author = {Spencer, Carrie and Abend, Stephanie and McHugh, Kevin J and Saint-Geniez, Magali}
}
@article {1295876,
	title = {Lymphatic malformation with acquired Horner syndrome in an infant},
	journal = {J Neurointerv Surg},
	volume = {10},
	number = {3},
	year = {2018},
	month = {2018 Mar},
	pages = {e2},
	abstract = {An infant presented with right upper eyelid ptosis and was subsequently diagnosed with acquired Horner syndrome. Further evaluation revealed a right-sided cervicothoracic lymphatic malformation. At 13 weeks of age, the child underwent percutaneous intracystic sclerotherapy with a mixture of sodium tetradecyl sulphate and ethanol. Twenty-one weeks after initial treatment, ophthalmic examination showed complete resolution of the blepharoptosis and pupillary miosis. Percutaneous sclerotherapy not only effectively treated the space-occupying lymphatic malformation but also reversed the Horner syndrome that was presumably induced by neural tension (more likely) or compression.},
	issn = {1759-8486},
	doi = {10.1136/neurintsurg-2017-013315.rep},
	author = {Spors, Birgit and Seemann, Joerg and Homer, Natalie and Fay, Aaron}
}
@article {988021,
	title = {New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.},
	journal = {Hum Mol Genet},
	year = {2017},
	abstract = {Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddw399},
	author = {Springelkamp, Henri{\"e}t and Iglesias, Adriana I and Mishra, Aniket and H{\"o}hn, Ren{\'e} and Wojciechowski, Robert and Khawaja, Anthony P and Nag, Abhishek and Wang, Ya Xing and Wang, Jie Jin and Cuellar-Partida, Gabriel and Gibson, Jane and Cooke Bailey, Jessica N and Vithana, Eranga N and Gharahkhani, Puya and Boutin, Thibaud and Ramdas, Wishal D and Zeller, Tanja and Luben, Robert N and Yonova-Doing, Ekaterina and Viswanathan, Ananth C and Yazar, Seyhan and Cree, Angela J and Haines, Jonathan L and Koh, Jia Yu and Souzeau, Emmanuelle and Wilson, James F and Amin, Najaf and M{\"u}ller, Christian and Venturini, Cristina and Kearns, Lisa S and Kang, Jae Hee and NEIGHBORHOOD Consortium and Tham, Yih Chung and Zhou, Tiger and van Leeuwen, Elisabeth M and Nickels, Stefan and Sanfilippo, Paul and Liao, Jiemin and Linde, Herma van der and Zhao, Wanting and van Koolwijk, Leonieke M E and Zheng, Li and Rivadeneira, Fernando and Baskaran, Mani and van der Lee, Sven J and Perera, Shamira and de Jong, Paulus T V M and Oostra, Ben A and Uitterlinden, Andr{\'e} G and Fan, Qiao and Hofman, Albert and Tai, E-Shyong and Vingerling, Johannes R and Sim, Xueling and Wolfs, Roger C W and Teo, Yik Ying and Lemij, Hans G and Khor, Chiea Chuen and Willemsen, Rob and Lackner, Karl J and Aung, Tin and Jansonius, Nomdo M and Montgomery, Grant and Wild, Philipp S and Young, Terri L and Burdon, Kathryn P and Hysi, Pirro G and Pasquale, Louis R and Wong, Tien Yin and Klaver, Caroline C W and Hewitt, Alex W and Jonas, Jost B and Mitchell, Paul and Lotery, Andrew J and Foster, Paul J and Vitart, Veronique and Pfeiffer, Norbert and Craig, Jamie E and Mackey, David A and Hammond, Christopher J and Wiggs, Janey L and Cheng, Ching-Yu and van Duijn, Cornelia M and Macgregor, Stuart}
}
@article {280821,
	title = {Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.},
	journal = {Nat Commun},
	volume = {5},
	year = {2014},
	month = {2014},
	pages = {4883},
	abstract = {Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.},
	issn = {2041-1723},
	doi = {10.1038/ncomms5883},
	author = {Springelkamp, Henri{\"e}t and H{\"o}hn, Ren{\'e} and Mishra, Aniket and Hysi, Pirro G and Khor, Chiea-Chuen and Loomis, Stephanie J and Bailey, Jessica N Cooke and Gibson, Jane and Thorleifsson, Gudmar and Janssen, Sarah F and Luo, Xiaoyan and Ramdas, Wishal D and Vithana, Eranga and Nongpiur, Monisha E and Montgomery, Grant W and Xu, Liang and Mountain, Jenny E and Gharahkhani, Puya and Lu, Yi and Amin, Najaf and Karssen, Lennart C and Sim, Kar-Seng and van Leeuwen, Elisabeth M and Iglesias, Adriana I and Verhoeven, Virginie J M and Hauser, Michael A and Loon, Seng-Chee and Despriet, Dominiek D G and Nag, Abhishek and Venturini, Cristina and Sanfilippo, Paul G and Schillert, Arne and Kang, Jae H and Landers, John and Jonasson, Fridbert and Cree, Angela J and van Koolwijk, Leonieke M E and Rivadeneira, Fernando and Souzeau, Emmanuelle and Jonsson, Vesteinn and Menon, Geeta and Blue Mountains Eye Study{\textemdash}GWAS group and Weinreb, Robert N and de Jong, Paulus T V M and Oostra, Ben A and Uitterlinden, Andr{\'e} G and Hofman, Albert and Ennis, Sarah and Thorsteinsdottir, Unnur and Burdon, Kathryn P and NEIGHBORHOOD Consortium and Wellcome Trust Case Control Consortium 2 (WTCCC2) and Spector, Timothy D and Mirshahi, Alireza and Saw, Seang-Mei and Vingerling, Johannes R and Teo, Yik-Ying and Haines, Jonathan L and Wolfs, Roger C W and Lemij, Hans G and Tai, E-Shyong and Jansonius, Nomdo M and Jonas, Jost B and Cheng, Ching-Yu and Aung, Tin and Viswanathan, Ananth C and Klaver, Caroline C W and Craig, Jamie E and Macgregor, Stuart and Mackey, David A and Lotery, Andrew J and Stefansson, Kari and Bergen, Arthur A B and Young, Terri L and Wiggs, Janey L and Pfeiffer, Norbert and Wong, Tien-Yin and Pasquale, Louis R and Hewitt, Alex W and van Duijn, Cornelia M and Hammond, Christopher J and Blue Mountains Eye Study-GWAS group and NEIGHBORHOOD Consortium and Wellcome Trust Case Control Consortium 2 WTCCC2}
}
@article {1363206,
	title = {Methods for culture of human corneal and conjunctival epithelia},
	journal = {Methods Mol Biol},
	volume = {945},
	year = {2013},
	month = {2013},
	pages = {31-43},
	abstract = {The surface of the eye is exposed to the outside world and is, thus, subject to surface abrasion, infections, and drying, cicatrizing diseases. Availability of in vitro methods for culture of the human corneal and conjunctival epithelia, which cover the ocular surface, is therefore important in understanding the biology of these epithelia and their response to disease/infections, as well as for providing human-relevant models for preclinical testing of potential therapeutic agents. The ensuing chapter describes several methods for primary culture of both corneal and conjunctival epithelia and culture of immortalized cell lines, and methods employed to induce differentiation in the cultured epithelia.},
	keywords = {Biomarkers, Cell Culture Techniques, Cell Differentiation, Cell Line, Cell Proliferation, Conjunctiva, Cornea, Epithelial Cells, Feeder Cells, Humans},
	issn = {1940-6029},
	doi = {10.1007/978-1-62703-125-7_3},
	author = {Spurr-Michaud, Sandra J and Gipson, Ilene K}
}
@article {382211,
	title = {Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images.},
	journal = {Biomed Opt Express},
	volume = {5},
	number = {10},
	year = {2014},
	month = {2014 Oct 1},
	pages = {3568-77},
	abstract = {We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100\% of cases with AMD, 100\% cases with DME, and 86.67\% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases.},
	issn = {2156-7085},
	doi = {10.1364/BOE.5.003568},
	author = {Srinivasan, Pratul P and Kim, Leo A and Mettu, Priyatham S and Cousins, Scott W and Comer, Grant M and Izatt, Joseph A and Farsiu, Sina}
}
@article {560191,
	title = {Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis.},
	journal = {Angiogenesis},
	volume = {18},
	number = {4},
	year = {2015},
	month = {2015 Oct},
	pages = {449-62},
	abstract = {Expression and activation of vascular endothelial growth factor receptor 2 (VEGFR-2) by VEGF ligands are the main events in the stimulation of pathological angiogenesis. VEGFR-2 expression is generally low in the healthy adult blood vessels, but its expression is markedly increased in the pathological angiogenesis. In this report, we demonstrate that phosducin-like 3 (PDCL3), a recently identified chaperone protein involved in the regulation of VEGFR-2 expression, is required for angiogenesis in zebrafish and mouse. PDCL3 undergoes N-terminal methionine acetylation, and this modification affects PDCL3 expression and its interaction with VEGFR-2. Expression of PDCL3 is regulated by hypoxia, the known stimulator of angiogenesis. The mutant PDCL3 that is unable to undergo N-terminal methionine acetylation was refractory to the effect of hypoxia. The siRNA-mediated silencing of PDCL3 decreased VEGFR-2 expression resulting in a decrease in VEGF-induced VEGFR-2 phosphorylation, whereas PDCL3 over-expression increased VEGFR-2 protein. Furthermore, we show that PDCL3 protects VEGFR-2 from misfolding and aggregation. The data provide new insights for the chaperone function of PDCL3 in angiogenesis and the roles of hypoxia and N-terminal methionine acetylation in PDCL3 expression and its effect on VEGFR-2.},
	issn = {1573-7209},
	doi = {10.1007/s10456-015-9468-3},
	author = {Srinivasan, Srimathi and Chitalia, Vipul and Meyer, Rosana D and Hartsough, Edward and Mehta, Manisha and Harrold, Itrat and Anderson, Nicole and Feng, Hui and Smith, Lois E H and Jiang, Yan and Costello, Catherine E and Rahimi, Nader}
}
@article {1109871,
	title = {Development of wound healing models to study TGFβ3{\textquoteright}s effect on SMA},
	journal = {Exp Eye Res},
	volume = {161},
	year = {2017},
	month = {2017 Aug},
	pages = {52-60},
	abstract = {The goal of this study was to test the efficacy of transforming growth factor beta 3 (TGFβ3) in reducing α-smooth muscle actin (SMA) expression in two models-an ex\&nbsp;vivo organ culture and an in\&nbsp;vitro 3D cell construct-both of which closely mimic an in\&nbsp;vivo environment. For the ex\&nbsp;vivo organ culture system, a central 6.0\&nbsp;mm corneal keratectomy was performed on freshly excised rabbit globes The corneas were then excised, segregated into groups treated with 1.0\&nbsp;ng/ml TGFβ1 or β3 (T1 or T3, respectively), and cultured for 2 weeks. The corneas were assessed for levels of haze and analyzed for SMA mRNA levels. For the 3D in\&nbsp;vitro model, rabbit corneal fibroblasts (RbCFs) were cultured for 4 weeks on poly-transwell membranes in Eagle{\textquoteright}s minimum essential media (EMEM)\&nbsp;+\&nbsp;10\% FBS\&nbsp;+\&nbsp;0.5\&nbsp;mM vitamin C\&nbsp;{\textpm}\&nbsp;0.1\&nbsp;ng/ml T1 or T3. At the end of 4 weeks, the constructs were processed for analysis by indirect-immunofluorescence (IF) and RT-qPCR. The RT-qPCR data showed that SMA mRNA expression in T3 samples for both models was significantly lower (p\&nbsp;\&lt;\&nbsp;0.05) than T1 treatment (around 3-fold in ex\&nbsp;vivo and 2-fold in constructs). T3 also reduced the amount of scarring in ex\&nbsp;vivo corneas as compared with the T1 samples. IF data from RbCF constructs confirmed that T3-treated samples had up to 4-fold (p\&nbsp;\&lt;\&nbsp;0.05) lower levels of SMA protein expression than samples treated with T1. These results show that T3 when compared to T1 decreases the expression of SMA in both ex\&nbsp;vivo organ culture and in\&nbsp;vitro 3D cell construct models. Understanding the mechanism of T3{\textquoteright}s action in these systems and how they differ from simple cell culture models, may potentially help in developing T3 as an anti-scarring therapy.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2017.06.005},
	author = {Sriram, Sriniwas and Tran, Jennifer A and Guo, Xiaoqing and Hutcheon, Audrey E K and Kazlauskas, Andrius and Zieske, James D}
}
@article {314201,
	title = {Assessment of anti-scarring therapies in ex vivo organ cultured rabbit corneas},
	journal = {Exp Eye Res},
	volume = {125},
	year = {2014},
	month = {2014 Aug},
	pages = {173-82},
	abstract = {The effects of a triple combination of siRNAs targeting key scarring genes were assessed using an ex\&nbsp;vivo organ culture model of excimer ablated rabbit corneas. The central 6\&nbsp;mm diameter region of fresh rabbit globes was ablated to a depth of 155 microns with an excimer laser. Corneas were excised, cultured at the air-liquid interface in defined culture medium supplemented with transforming growth factor beta 1 (TGFB1), and treated with either 1\% prednisolone acetate or with 22.5\&nbsp;μM cationic nanoparticles complexed with a triple combination of siRNAs (NP-siRNA) targeting TGFB1, TGFB Receptor (TGFBR2) and connective tissue growth factor (CTGF). Scar formation was measured using image analysis of digital images and levels of smooth muscle actin (SMA) were assessed in ablated region of corneas using qRT-PCR and immunostaining. Ex\&nbsp;vivo cultured corneas developed intense haze-like scar in the wounded areas and levels of mRNAs for pro-fibrotic genes were significantly elevated 3-8 fold in wounded tissue compared to unablated corneas. Treatment with NP-siRNA or steroid significantly reduced quantitative haze levels by 55\% and 68\%, respectively, and reduced SMA mRNA and immunohistostaining. This ex\&nbsp;vivo corneal culture system reproduced key molecular patterns of corneal scarring and haze formation generated in rabbits. Treatment with NP-siRNAs targeting key scarring genes or an anti-inflammatory steroid reduced corneal haze and SMA mRNA and protein.},
	keywords = {Actins, Analysis of Variance, Animals, Anti-Inflammatory Agents, Cicatrix, Connective Tissue Growth Factor, Cornea, Corneal Diseases, Disease Models, Animal, Immunohistochemistry, Laser Therapy, Nanoparticles, Organ Culture Techniques, Prednisolone, Rabbits, Receptors, Transforming Growth Factor beta, RNA, Small Interfering, Transforming Growth Factor beta1},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2014.06.014},
	author = {Sriram, Sriniwas and Gibson, Daniel J and Robinson, Paulette and Pi, Liya and Tuli, Sonal and Lewin, Alfred S and Schultz, Gregory}
}
@article {1137906,
	title = {Increased Survival and Partly Preserved Cognition in a Patient With ACO2-Related Disease Secondary to a Novel Variant},
	journal = {J Child Neurol},
	volume = {32},
	number = {9},
	year = {2017},
	month = {2017 Aug},
	pages = {840-845},
	abstract = {ACO2 encodes aconitase 2, catalyzing the second step of the tricarboxylic acid. To date, there are only 6 reported families with 5 unique ACO2 mutations. Affected individuals can develop intellectual disability, epilepsy, brain atrophy, hypotonia, ataxia, optic atrophy, and retinal degeneration. Here, we report an 18-year-old boy with a novel ACO2 variant discovered on whole-exome sequencing. He presented with childhood-onset ataxia, impaired self-help skills comparable to severe-profound intellectual disability, intractable epilepsy, cerebellar atrophy, peripheral neuropathy, optic atrophy, and pigmentary retinopathy. His variant is the sixth unique ACO2 mutation. In addition, compared to mild cases (isolated optic atrophy) and severe cases (infantile death), our patient may be moderately affected, evident by increased survival and some preserved cognition (ability to speak full sentences and follow commands), which is a novel presentation. This case expands the disease spectrum to include increased survival with partly spared cognition.},
	issn = {1708-8283},
	doi = {10.1177/0883073817711527},
	author = {Srivastava, Siddharth and Gubbels, Cynthia S and Dies, Kira and Fulton, Anne and Yu, Timothy and Sahin, Mustafa}
}
@article {382631,
	title = {Correlation of clinical profile and specific histopathological features of temporal artery biopsies.},
	journal = {J Neuroophthalmol},
	volume = {35},
	number = {2},
	year = {2015},
	month = {2015 Jun},
	pages = {127-33},
	abstract = {BACKGROUND: This study sought to correlate the clinical features of patients with giant cell arteritis (GCA) who present with ophthalmic symptoms and signs, with 2 specific histopathological findings-the presence of giant cells and arterial wall neoangiogenesis. The goal was to assess if these pathological features might be useful in guiding the approach to patient management. METHODS: Medical charts were retrospectively reviewed from 58 patients who underwent a temporal artery biopsy at a single institution. Detailed information was collected about the clinical presentation and course, with an emphasis on visual function. Histopathological and immunohistochemical techniques were used to examine temporal artery biopsies for evidence of inflammation. Correlations were made between the clinical data and the presence of giant cells and neoangiogenesis. RESULTS: Twenty-one (34\%) biopsies were positive for inflammation consistent with GCA. Although the percentage of positive biopsies with giant cells was high, neither the presence of giant cells nor neoangiogenesis was predictive of a patient{\textquoteright}s presenting visual symptoms, severity and bilaterality of vision loss, other ophthalmic manifestations of GCA, presence of headache or jaw claudication, or erythrocyte sedimentation rate. Giant cells were more common in patients with recent weight loss. Immunohistochemistry confirmed diagnoses but did not alter the clinical course or treatment plan. CONCLUSIONS: There was no correlation between the clinical, specifically visual, features of GCA and the presence or absence of giant cells or neoangiogenesis in temporal artery biopsy specimens. Although the presence of neoangiogenesis may be important in the pathogenesis of GCA, our study showed no correlation between this finding and the clinical course.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000213},
	author = {Stacy, Rebecca C and Gilbert, Aubrey L and Rizzo, Joseph F}
}
@article {541326,
	title = {Posterior Necrotizing Scleritis Presenting as Sectoral Chorioretinitis},
	journal = {Ocul Immunol Inflamm},
	volume = {23},
	number = {5},
	year = {2015},
	month = {2015},
	pages = {412-5},
	keywords = {Chorioretinitis, Diagnosis, Differential, Female, Fluorescein Angiography, Fundus Oculi, Humans, Magnetic Resonance Imaging, Middle Aged, Necrosis, Sclera, Scleritis, Ultrasonography},
	issn = {1744-5078},
	doi = {10.3109/09273948.2014.896467},
	author = {Stacy, Rebecca C and Uchiyama, Eduardo and Jakobiec, Frederick A and Sobrin, Lucia}
}
@article {1328904,
	title = {A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma},
	journal = {Am J Ophthalmol},
	volume = {192},
	year = {2018},
	month = {2018 Aug},
	pages = {113-123},
	abstract = {PURPOSE: To assess the clinical safety, tolerability, and efficacy of topically administered MGV354, a soluble guanylate cyclase (sGC) activator, in patients with ocular hypertension (OH) or glaucoma. DESIGN: Double-masked, randomized, and vehicle-controlled study. METHODS: Parts 1 and 2 evaluated safety and tolerability to identify the maximum tolerated dose (MTD) of once-daily MGV354 in 32 healthy volunteers (Part 1) and 16 patients with OH or glaucoma (Part 2) at a single clinical site. Part 3 was a multisite trial that evaluated intraocular pressure (IOP)-lowering efficacy of the MTD administered nightly for 1\&nbsp;week in 50 patients with minimum IOP of 24\&nbsp;mm Hg at 8 AM, with a main outcome measure of mean diurnal IOP at day 8 compared to baseline (ClinicalTrials.govNCT02743780). RESULTS: There was no difference in favor of MGV354 for IOP lowering; change from baseline to day 8 in mean diurnal IOP was -0.6\&nbsp;mm Hg for MGV354-treated patients and -1.1\&nbsp;mm Hg for vehicle-treated patients in Part 3, with a confidence interval of -0.7 to 1.7. The most common adverse events reported after MGV354 administration were conjunctival and ocular hyperemia. CONCLUSIONS: Overall, MGV354 0.1\% demonstrated no statistically significant effect compared to vehicle in lowering IOP based on the study{\textquoteright}s main outcome measure. MGV354 produced ocular hyperemia consistent with its pharmacology.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.05.015},
	author = {Stacy, Rebecca and Huttner, Kenneth and Watts, Jen and Peace, James and Wirta, David and Walters, Tom and Sall, Kenneth and Seaman, John and Ni, Xiao and Prasanna, Ganesh and Mogi, Muneto and Adams, Christopher and Yan, Jing-He and Wald, Michael and He, Yunsheng and Newton, Ronald and Kolega, Randall and Grosskreutz, Cynthia}
}
@article {669251,
	title = {A Critical Analysis of Eleven Periocular Lobular Capillary Hemangiomas in Adults.},
	journal = {Am J Ophthalmol},
	year = {2016},
	month = {2016 Mar 10},
	abstract = {PURPOSE: To provide a critical analysis of a series of periocular lobular capillary hemangiomas in adults, outlining characteristic clinical and histopathologic patterns in comparison with those of other vascular tumors of adults and children. DESIGN: Retrospective, observational case series. METHODS: Review of clinical data, hematoxylin and eosin stained sections and immunohistochemical studies of smooth muscle actin (SMA), D2-40, CD34, and glucose transporter 1 (GLUT-1). RESULTS: The 7 female and 4 male patients were diagnosed with periocular lobular capillary hemangioma at a median age of 39 years (range of 17-82 years). The tumors were small (3-14 mm, median size 6 mm) and well-circumscribed, arose over the course of weeks to months and developed most commonly in the canthal region, followed by the upper eyelid skin. The tumors were all composed microscopically of repeating units of various sizes (lobules) consisting of CD34-postive, GLUT-1-negative endothelial cells and SMA-positive pericytes arranged in macro- or micro-lobules. Some foci also exhibited ectatic vessels or diffuse, non-lobular capillary proliferations. Excision was curative without recurrence. CONCLUSION: Although capillary hemangiomas are more common in children, lobular capillary hemangiomas can also arise in the periocular region of adults. Some histopathologic features of these lesions are shared with those of infantile hemangioma and tufted angioma of children, but features of the clinical presentation and the results of immunohistochemical staining patterns are distinctive.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.03.010},
	author = {Stagner, Anna M and Jakobiec, Frederick A}
}
@article {836976,
	title = {p16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma.},
	journal = {Am J Ophthalmol},
	volume = {170},
	year = {2016},
	month = {2016 Oct},
	pages = {168-175},
	abstract = {PURPOSE: To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA in\&nbsp;situ hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. RESULTS: The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of \&gt;70\% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9\%). The selected 18 p16-positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. CONCLUSION: No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.07.012},
	author = {Stagner, Anna M and Afrogheh, Amir H and Jakobiec, Frederick A and Iacob, Codrin E and Grossniklaus, Hans E and Deshpande, Vikram and Maske, Christopher and Hiss, Donovan C and Faquin, William C}
}
@article {397876,
	title = {Peripheral Nerve Sheath Tumors of the Eyelid Dermis: A Clinicopathologic and Immunohistochemical Analysis.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {1},
	year = {2016},
	month = {2016 Jan-Feb},
	pages = {40-5},
	abstract = {PURPOSE: To determine the incidences, clinical features, and detailed histopathologic and immunohistochemical findings of 10 peripheral nerve tumors (isolated neurofibromas, solitary circumscribed neuromas [SCNs], and schwannomas) localized to the eyelid dermis. METHODS: In this retrospective clinicopathologic study, clinical records and paraffin sections subjected to hematoxylin and eosin, Masson trichrome, periodic acid-Schiff, reticulin, and Alcian blue staining were critically reviewed from each case. Additional paraffin sections were immunoreacted for S100, neurofilament, CD34, epithelial membrane antigen (EMA), glucose transporter-1 (glut-1), and calretinin. RESULTS: Ten patients with a median age of 57 years had solitary, small, flesh-colored papules, 70\% at the eyelid margin. Microscopically, they were diagnosed either as a SCN or an isolated neurofibroma. SCN was diffusely S100-positive (and sometimes diffusely calretinin-positive) with myriad neurofilaments. Fascicles of cells were separated by CD34-positive septa, and the lesions were surrounded by a glut-1/EMA-positive capsule. Neurofibromas were calretinin-negative and had a moderate number of S100-positive cells, with widely scattered neurofilaments, many CD34-postive intermixed cells, and no capsule. No schwannomas were diagnosed. CONCLUSIONS: Peripheral nerve tumors of the eyelid have a distinct clinical presentation at the eyelid margin. Careful histopathologic and immunohistochemical studies can reliably separate the entities in the categories of isolated neurofibroma, SCN, and schwannoma when the last occurs. These distinctions can have important systemic implications.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000424},
	author = {Stagner, Anna M and Jakobiec, Frederick A}
}
@article {416876,
	title = {Conjunctival inverted squamous papilloma: A case report with immunohistochemical analysis and review of the literature.},
	journal = {Surv Ophthalmol},
	volume = {60},
	number = {3},
	year = {2015},
	month = {2015 May-Jun},
	pages = {263-268},
	abstract = {A 63-year-old man presented with an asymptomatic papillary, sessile lesion of the juxtalimbal bulbar conjunctiva that was surgically excised with cryotherapy. Histopathologically, the lesion created some diagnostic confusion as it displayed an endophytic, or inverted, growth pattern-with squamous cells pushing into the substantia propria around fibrovascular cores, but without significant cytologic atypia, consistent with a conjunctival inverted papilloma (IP). Unlike previously reported cases of conjunctival IP, there were no goblet cells or cysts within the tumor. Immunostaining was diffusely positive for cytokeratin (CK) 7, and CK14 stained the basilar and suprabasilar cells, as in normal conjunctiva. CK17 weakly and non-uniformly stained the tumor, ruling out a dysplasia, which is usually strongly positive. The lesion{\textquoteright}s cytokeratin profile therefore paralleled that of normal conjunctiva. The proliferation index with Ki67 nuclear staining was extremely low (\&lt;1\%), as was p53 nuclear staining (10-20\%), both in contrast to squamous cell dysplasias or carcinomas that have a much higher percentage of positive cells. The lesion was negative for human papillomavirus subtypes associated with squamous neoplasias including carcinomas. We review the previous literature devoted to this comparatively rare condition and contrast its benign clinical course with that of inverted papillomas of the sinonasal, lacrimal drainage, and genitourinary systems and provide a set of criteria for establishing the diagnosis.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2014.10.004},
	author = {Stagner, Anna M and Jakobiec, Frederick A and Chi, Anthony and Bradshaw, Scott H and Mendoza, Silvino Diaz}
}
@article {560226,
	title = {Invasive Squamous Cell Carcinoma With Clear Cell Change of the Eyelid Arising in a Seborrheic Keratosis.},
	journal = {JAMA Ophthalmol},
	year = {2015},
	month = {2015 Oct 1},
	pages = {1-2},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.3439},
	author = {Stagner, Anna M and Jakobiec, Frederick A and Iwamoto, Mami A}
}
@article {439631,
	title = {Demonstration of a Borst-Jadassohn-Like Phenomenon in Sebaceous Carcinoma of the Eyelid.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2015},
	month = {2015 May 27},
	abstract = {A 77-year-old male presented with a diffuse, papular erythematous conjunctival mass that demonstrated on pathologic examination lobules of tumor in the conjunctival substantia propria and tarsus. The cells displayed numerous cytoplasmic vacuoles with extreme nuclear pleomorphism, consistent with sebaceous carcinoma. The overlying palpebral conjunctival epithelium exhibited regions of carcinoma in situ containing some vacuolated cells, alternating with a more classical appearance of pagetoid spread among normal surviving keratinocytes. Further analysis disclosed vesicular positivity for adipophilin and positive nuclear staining for androgen receptor. One tumor focus harbored exaggerated collections of intraepithelial tumor cells. These simulated the Borst-Jadassohn phenomenon of large nests of alien appearing cells normally encountered within the epidermis of the skin. This is the first description of this pattern created by an eyelid sebaceous carcinoma growing within the conjunctival epithelium.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000493},
	author = {Stagner, Anna M and Jakobiec, Frederick A}
}
@article {280801,
	title = {Ruptured canthal steatocystoma simplex presenting as a lacrimal sac mass.},
	journal = {Clin Experiment Ophthalmol},
	year = {2014},
	month = {2014 Sep 29},
	issn = {1442-9071},
	doi = {10.1111/ceo.12441},
	author = {Stagner, Anna M and Jakobiec, Frederick A and Yoon, Michael K}
}
@article {591226,
	title = {Primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin: Diagnostic clues and distinction from other ocular adnexal diseases.},
	journal = {Surv Ophthalmol},
	volume = {61},
	number = {3},
	year = {2016},
	month = {2016 May-Jun},
	pages = {333-8},
	abstract = {A 60-year-old man developed a rubbery thickening and erythema of his left lateral upper and lower eyelids and lateral canthus over several months. He was treated for an extended period of time for blepharitis and chalazia. Incisional biopsy eventually disclosed microscopically a hypercellular lymphoid population sparing the epidermis that surrounded adnexal structures and infiltrated between orbicularis muscle fibers. Immunohistochemically, the lesion was found to be composed of neoplastic, kappa-restricted B cells with an equal number of reactive T cells and small reactive follicles. The diagnosis was a primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin (EMZL). We review the distinguishing clinical, histopathologic, and immunohistochemical features of cutaneous EMZL and contrast those with EMZL of other ocular adnexal sites. Also offered is a differential diagnosis of cutaneous lymphomas of the eyelid skin, which are predominately T-cell lesions.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2015.10.007},
	author = {Stagner, Anna M and Jakobiec, Frederick A and Freitag, Suzanne K}
}
@article {1043281,
	title = {Primary orbital synovial sarcoma: A clinicopathologic review with a differential diagnosis and discussion of molecular genetics},
	journal = {Surv Ophthalmol},
	volume = {62},
	number = {2},
	year = {2017},
	month = {2017 Mar - Apr},
	pages = {227-236},
	abstract = {Synovial sarcoma is a soft-tissue sarcoma of the extremities developing in young adults that has rarely been reported in the orbit. Synovial sarcoma is associated with a unique translocation, resulting in an SYT-SSX fusion gene. We analyze 7 published periocular cases, together with the current one, to gain a better appreciation of the features of the tumor in this location and to compare the findings with those derived from nonophthalmic studies. An inferior orbital mass developed in a 31-year-old woman after experiencing periorbital and hemifacial pain for more than a decade. Radiographically, the mass was circumscribed and displayed coarse internal calcifications. A large but subtotal excision with histopathologic examination disclosed a primitive tumor composed of spindled and ovoid cells. Immunohistochemistry demonstrated positivity for nuclear transducin-like enhancer of split 1 and membranous CD99, typical for synovial sarcoma. Fluorescence in situ hybridization identified a (X,18) translocation in the tumor cells. The patient underwent postoperative adjuvant proton beam radiotherapy with a good response that has been maintained during 1 year of follow-up. Orbital soft-tissue tumors of all types are increasingly identified by their distinctive genetic signatures that offer more specificity than standard immunohistochemical tests.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.09.001},
	author = {Stagner, Anna M and Jakobiec, Frederick A and Fay, Aaron}
}
@article {1814411,
	title = {Histopathologic clues to the etiopathogenesis of orbital inflammatory disease: Idiopathic, IgG4-related, neoplastic, autoimmune and beyond},
	journal = {Semin Diagn Pathol},
	volume = {41},
	number = {2},
	year = {2024},
	month = {2024 Mar},
	pages = {66-71},
	abstract = {Orbital inflammatory diseases represent a heterogenous group of idiopathic, autoimmune-related, and sometimes neoplastic conditions with overlapping clinical and histopathologic features, as well as variable levels of IgG4-positive plasma cells detected within tissue biopsies. Some histopathologic features, especially in an appropriate clinical context, may point to a specific diagnosis in a given patient. Diagnoses of non-specific orbital inflammation, orbital inflammation related to autoimmune diseases such as granulomatosis with polyangiitis and IgG4-related disease, lymphoma, and xanthogranulomatous diseases are discussed, contrasted and illustrated.},
	keywords = {Autoimmune Diseases, Humans, Immunoglobulin G, Immunoglobulin G4-Related Disease, Inflammation, Lymphoma},
	issn = {0740-2570},
	doi = {10.1053/j.semdp.2024.01.011},
	author = {Stagner, Anna M}
}
@article {1364551,
	title = {SOCS3 is an endogenous inhibitor of pathologic angiogenesis},
	journal = {Blood},
	volume = {120},
	number = {14},
	year = {2012},
	month = {2012 Oct 04},
	pages = {2925-9},
	abstract = {Inflammatory cytokines and growth factors drive angiogenesis independently; however, their integrated role in pathologic and physiologic angiogenesis is not fully understood. Suppressor of cytokine signaling-3 (SOCS3) is an inducible negative feedback regulator of inflammation and growth factor signaling. In the present study, we show that SOCS3 curbs pathologic angiogenesis. Using a Cre/Lox system, we deleted SOCS3 in vessels and studied developmental and pathologic angiogenesis in murine models of oxygen-induced retinopathy and cancer. Conditional loss of SOCS3 leads to increased pathologic neovascularization, resulting in pronounced retinopathy and increased tumor size. In contrast, physiologic vascularization is not regulated by SOCS3. In vitro, SOCS3 knockdown increases proliferation and sprouting of endothelial cells costimulated with IGF-1 and TNFα via reduced feedback inhibition of the STAT3 and mTOR pathways. These results identify SOCS3 as a pivotal endogenous feedback inhibitor of pathologic angiogenesis and a potential therapeutic target acting at the converging crossroads of growth factor- and cytokine-induced vessel growth.},
	keywords = {Animals, Blotting, Western, Carcinoma, Lewis Lung, Cell Proliferation, Endothelium, Vascular, Hypoxia, Insulin-Like Growth Factor I, Integrases, Male, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, Paraneoplastic Syndromes, Ocular, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Signal Transduction, STAT3 Transcription Factor, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins, TOR Serine-Threonine Kinases, Tumor Necrosis Factor-alpha},
	issn = {1528-0020},
	doi = {10.1182/blood-2012-04-422527},
	author = {Stahl, Andreas and Joyal, Jean-Sebastian and Chen, Jing and Sapieha, Przemyslaw and Juan, Aimee M and Hatton, Colman J and Pei, Dorothy T and Hurst, Christian G and Seaward, Molly R and Krah, Nathan M and Dennison, Roberta J and Greene, Emily R and Boscolo, Elisa and Panigrahy, Dipak and Smith, Lois E H}
}
@article {1295877,
	title = {Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity: A Randomized Clinical Trial},
	journal = {JAMA Pediatr},
	volume = {172},
	number = {3},
	year = {2018},
	month = {2018 Mar 01},
	pages = {278-286},
	abstract = {Importance: Anti-vascular endothelial growth factor (VEGF) therapies are a novel treatment option in retinopathy of prematurity (ROP). Data on dosing, efficacy, and safety are insufficient. Objective: To investigate lower doses of anti-VEGF therapy with ranibizumab, a substance with a significantly shorter systemic half-life than the standard treatment, bevacizumab. Design, Setting, and Participants: This randomized, multicenter, double-blind, investigator-initiated trial at 9 academic medical centers in Germany compared ranibizumab doses of 0.12 mg vs 0.20 mg in infants with bilateral aggressive posterior ROP; ROP stage 1 with plus disease, 2 with plus disease, or 3 with or without plus disease in zone I; or ROP stage 3 with plus disease in posterior zone II. Patients were recruited between September 2014 and August 2016. Twenty infants were screened and 19 were randomized. Interventions: All infants received 1 baseline ranibizumab injection per eye. Reinjections were allowed in case of ROP recurrence after at least 28 days. Main Outcomes and Measures: The primary end point was the number of infants who did not require rescue therapy at 24 weeks. Key secondary end points included time-to-event analyses, progression of physiologic vascularization, and plasma VEGF levels. Stages of ROP were photodocumented and reviewed by an expert committee. Results: Nineteen infants with ROP were enrolled (9 [47.4\%] female; median [range] postmenstrual age at first treatment, 36.4 [34.7-39.7] weeks), 3 of whom died during the study (1 in the 0.12-mg group and 2 in the 0.20-mg group). Of the surviving infants, 8 (88.9\%) (17 eyes [94.4\%]) in the 0.12-mg group and 6 (85.7\%) (13 eyes [92.9\%]) in the 0.20-mg group did not require rescue therapy. Both ranibizumab doses were equally successful in controlling acute ROP (Cochran-Mantel-Haenszel analysis; odds ratio, 1.88; 95\% CI, 0.26-13.49; P = .53). Physiologic intraretinal vascularization was superior in the 0.12-mg group. The VEGF plasma levels were not systematically altered in either group. Conclusions and Relevance: This pilot study demonstrates that ranibizumab is effective in controlling acute ROP and that 24\% of the standard adult dose (0.12 mg) appears equally effective as 40\% (0.20 mg). Superior vascularization of the peripheral retina with 0.12 mg of ranibizumab indicates that the lower dose may be favorable. Unchanged plasma VEGF levels point toward a limited systemic drug exposure after ranibizumab. Trial Registration: clinicaltrials.gov Identifier: NCT02134457 and clinicaltrialsregister.eu Identifier: 2013-002539-13.},
	issn = {2168-6211},
	doi = {10.1001/jamapediatrics.2017.4838},
	author = {Stahl, Andreas and Krohne, Tim U and Eter, Nicole and Oberacher-Velten, Isabel and Guthoff, Rainer and Meltendorf, Synke and Ehrt, Oliver and Aisenbrey, Sabine and Roider, Johann and Gerding, Heinrich and Jandeck, Claudia and Smith, Lois E H and Walz, Johanna M and Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) Study Group}
}
@article {1474219,
	title = {Lack of Correlation between Number of Antiretinal Antibodies and Clinical Outcome Measures in Autoimmune Retinopathy Patients},
	journal = {Ophthalmol Retina},
	volume = {3},
	number = {11},
	year = {2019},
	month = {2019 Nov},
	pages = {1007-1009},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.06.007},
	author = {Stanwyck, Lynn K and Moussa, Kareem and Chan, Weilin and Aitken, Phil A and Sobrin, Lucia}
}
@article {1466918,
	title = {Predictive value of genetic testing for inherited retinal diseases in patients with suspected atypical autoimmune retinopathy},
	journal = {Am J Ophthalmol Case Rep},
	volume = {15},
	year = {2019},
	month = {2019 Sep},
	pages = {100461},
	abstract = {Purpose: The clinical features of autoimmune retinopathy (AIR) can resemble and be difficult to differentiate from inherited retinal degenerations (IRDs). Misdiagnosis of an IRD as AIR causes unnecessary treatment with immunosuppressive agents. The purpose of this study is to calculate the predictive value of genetic testing for IRDs in patients with suspected AIR and provide clinical examples where genetic testing has been useful. Methods: We identified patients seen at MEEI between April 2013 and January 2017 for whom the differentiation of AIR vs. IRDs was difficult based on clinical assessment alone. All patients had some atypical features for AIR, but tested positive for anti-retinal antibodies. Within this group, we identified six patients who had genetic testing for IRDs with the Genetic Eye Disease panel for retinal genes (GEDi-R). We calculated the positive predictive value (PPV) and negative predictive value (NPV) of genetic testing in a population with approximately equal numbers of IRD and AIR patients. Results: Six patients had clinical features that made distinguishing between IRDs and AIR on a clinical basis difficult and were sent for genetic testing: four women and two men with a mean age of 59.5 years. In two of these six patients, genetic diagnoses were made based upon the identification of known pathogenic variants in the common IRD genes and . Two patients had variants of unknown significance within genes associated with IRDs, and the other two had no relevant genetic findings. Given the 60\% sensitivity and 3\% false positive rate for GEDi-R testing and assuming a 50\% pre-test probability of having an IRD, the PPV for GEDi-R for detecting IRD is 95.2\% and the NPV is 70.8\%. Conclusions and Importance: In patients for whom the differential diagnosis of AIR and IRDs is unclear based on clinical information, genetic testing can be a valuable tool when it identifies an IRD, sparing the patient unnecessary immunosuppressive treatment. However, the test has a low NPV so a negative genetic testing result does not confidently exclude IRD as the true diagnosis.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2019.100461},
	author = {Stanwyck, Lynn K and Place, Emily M and Comander, Jason and Huckfeldt, Rachel M and Sobrin, Lucia}
}
@article {1125391,
	title = {TFOS DEWS II Epidemiology Report},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {334-365},
	abstract = {The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50\%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.05.003},
	author = {Stapleton, Fiona and Alves, Monica and Bunya, Vatinee Y and Jalbert, Isabelle and Lekhanont, Kaevalin and Malet, Florence and Na, Kyung-Sun and Schaumberg, Debra and Uchino, Miki and Vehof, Jelle and Viso, Eloy and Vitale, Susan and Jones, Lyndon}
}
@article {1263411,
	title = {Postoperative Complications of Dermis-Fat Autografts in the Anophthalmic Socket},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 16},
	pages = {1-4},
	abstract = {Reconstruction of the anophthalmic socket allows the use of an ocular prosthesis and rehabilitation of facial appearance. Dermis-fat grafting is one option in volume augmentation of the anophthalmic socket and presents unique benefits, including increased surface area within the socket and the ability to grow with pediatric patients. Postoperative complications of this procedure are relatively common. Minor complications, such as graft hirsutism, keratinization, and conjunctival cysts or granulomas, are managed easily by observation or simple intervention. Major complications, such as graft atrophy, infection, or ulceration, may prevent good prosthesis fit and may require return to the operating room.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353830},
	author = {Starks, Victoria and Freitag, Suzanne K}
}
@article {988026,
	title = {Human Bot Fly Infestation of the Eyelid.},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2017},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000859},
	author = {Starks, Victoria and Durand, Marlene and Ryan, Edward and Lefebvre, Daniel}
}
@article {1528426,
	title = {Prophylactic internal limiting membrane peeling during rhegmatogenous retinal detachment surgery},
	journal = {Acta Ophthalmol},
	volume = {99},
	number = {4},
	year = {2021},
	month = {2021 Jun},
	pages = {e619-e620},
	issn = {1755-3768},
	doi = {10.1111/aos.14560},
	author = {Starr, Matthew R and Obeid, Anthony and Gao, Xinxiao and Ryan, Edwin H and Shah, Gaurav K and Ryan, Claire and Madhava, Malika L and Maloney, Sean M and Adika, Adam Z and Peddada, Krishi V and Sioufi, Kareem and Ammar, Michael and Patel, Luv G and Forbes, Nora J and Capone, Antonio and Emerson, Geoffrey G and Joseph, Daniel P and Eliott, Dean and Regillo, Carl D and Hsu, Jason and Gupta, Omesh P and Yonekawa, Yoshihiro and Primary Retinal Detachment Outcomes (PRO) Study Group}
}
@article {1603842,
	title = {Dry eye disease flares: A rapid evidence assessment},
	journal = {Ocul Surf},
	volume = {22},
	year = {2021},
	month = {2021 Jul 22},
	pages = {51-59},
	abstract = {PURPOSE: Characteristics of periodic flares of dry eye disease (DED) are not well understood. We conducted a rapid evidence assessment to identify evidence for and characteristics of DED flares. METHODS: Literature searches were performed in Embase{\textregistered} via Ovid{\textregistered}, MEDLINE{\textregistered}, and PubMed{\textregistered}. Clinical trials and observational studies published 2009-2019 were included if they investigated patients aged >=18 years with clinically diagnosed DED who experienced a flare, defined as a temporary or transient episode of increased ocular discomfort, typically lasting days to a few weeks. Triggers of flares, patient-reported outcomes (symptoms), clinician-measured outcomes (signs), and changes in tear molecules were captured. RESULTS: Twenty-one publications that included 22 studies met inclusion criteria. Five observational studies described evidence of DED flares in daily life, 5 studies reported changes following cataract/refractive surgery in patients with preoperative DED, and 12 studies employed controlled environment (CE) models. Real-world triggers of DED flares included air conditioning, wind, reading, low humidity, watching television, and pollution. CE chambers (dry, moving air) and surgery also triggered DED flares. Exacerbations of symptoms and signs of DED, assessed through varied measures, were reported during flares. Across studies, matrix metalloproteinase-9 and interleukin-6 increased and epidermal growth factor decreased during DED flares. CONCLUSIONS: Evidence from 22 studies identified triggers and characteristics of DED flares. Further research is needed to assist clinicians in early diagnosis and treatment of patients experiencing flares.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.07.001},
	author = {Starr, Christopher E and Dana, Reza and Pflugfelder, Stephen C and Holland, Edward J and Zhang, Steven and Owen, Desiree and Brazzell, Kim}
}
@article {1806671,
	title = {Early recurrence of macular schisis in X-linked retinoschisis treated with vitrectomy for rhegmatogenous retinal detachment under silicone oil: case report and brief literature review},
	journal = {Ther Adv Ophthalmol},
	volume = {16},
	year = {2024},
	month = {2024 Jan-Dec},
	pages = {25158414241232261},
	abstract = {X-linked retinoschisis (XLRS) is an inherited retinal degeneration affecting males, characterized by splitting of the retinal layers. We herein present the outcomes of surgical treatment in a case of XLRS complicated by rhegmatogenous retinal detachment (RRD). A 22-year-old male presented to the emergency department due to decreased visual acuity and visual field defect in his left eye Oculus Sinister (OS) of 1 week duration. The patient reported an early onset retinal degeneration and decreased visual acuity in both eyes since childhood in his past ocular history. Upon presentation, best corrected visual acuity (BCVA) was 6/30 on the right eye Oculus Dexter (OD) and 6/120 OS. Fundus examination revealed areas of peripheral retinal schisis, and the characteristic spoke wheel pattern on the macula of both eyes. In OS, a temporal RRD involving the macula was identified. The patient underwent surgical treatment with pars plana vitrectomy with internal limiting membrane (ILM) peeling, endolaser, and silicone oil (SO) tamponade. BCVA in OS improved to 6/60 and schistic cavities resolution was observed in the immediate postoperative period. The patient{\textquoteright}s BCVA further improved to 6/19 at 1 month, as foveal anatomy showed relative improvement. However, there was a rapid reappearance of schisis spaces in the macular area at this point, which was also followed by progressive deterioration of foveal schisis by 3 months post-operatively. The resorption and recurrence of lamellar macular schisis changes after ILM peel and presence of SO, highlights that although XLRS findings can temporarily improve upon surgical intervention, the pathogenetic mechanisms contributing to disease phenotype remain to be elucidated.},
	issn = {2515-8414},
	doi = {10.1177/25158414241232261},
	author = {Stavrakas, Panagiotis and Tsapardoni, Foteini and Karmiris, Efthymios and Iatropoulos, Ioannis and Kounas, Konstantinos and Lygeros, Spyridon and Kozobolis, Vassilios and Vavvas, Demetrios G}
}
@article {416891,
	title = {Bupropion Use and Risk of Open-Angle Glaucoma among Enrollees in a Large U.S. Managed Care Network.},
	journal = {PLoS One},
	volume = {10},
	number = {4},
	year = {2015},
	month = {2015},
	pages = {e0123682},
	abstract = {OBJECTIVE: Tumor Necrosis Factor (TNF) mediates retinal ganglion cell death in glaucoma. Anti-TNF drugs are neuroprotective in an animal model of glaucoma. It is unclear whether medications with anti-TNF properties such as bupropion have an impact on the risk of developing open-angle glaucoma (OAG) in humans. The purpose of this study is to determine whether bupropion use alters the risk of developing OAG. METHODS: Claims data for beneficiaries age >=35 years with no pre-existing OAG enrolled in a large nationwide U.S. managed care network continuously for >=4 years between 2001-2011 was analyzed to identify patients who had been newly-diagnosed with OAG. The amount of bupropion use as captured from outpatient pharmacy claims over a four-year period was also quantified for each beneficiary. Multivariable Cox regression modeling assessed the impact of bupropion and other antidepressant medications on the risk of developing OAG with adjustment for sociodemographic characteristics of the enrollees along with medical and ocular comorbidities. RESULTS: Of 638,481 eligible enrollees, 15,292 (2.4\%) developed OAG. After adjustment for confounding factors including use of other antidepressant medication classes, each additional month of bupropion use was associated with a 0.6\% reduced risk of OAG (HR = 0.994, (95\% CI: 0.989-0.998), p = 0.007). Compared to nonusers, those with 24-48 months of bupropion use had a 21\% reduced hazard (HR=0.79, (CI: 0.65-0.94), p = 0.0099) of OAG. This association did not differ among persons taking bupropion for depression or for other reasons (p-interaction = 0.82). There was no significant association between use of tricyclic antidepressants (HR = 1.000, (CI: 0.997-1.004), p = 0.95) or selective serotonin reuptake inhibitors (HR = 0.999, (CI: 0.997-1.001), p = 0.39) and development of OAG. CONCLUSION: These findings suggest bupropion use may be beneficial in reducing the risk of OAG. If prospective studies confirm the findings of this analysis, this may identify a novel therapeutic target for OAG.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0123682},
	author = {Stein, Joshua D and Talwar, Nidhi and Kang, Jae H and Okereke, Olivia I and Wiggs, Janey L and Pasquale, Louis R}
}
@article {1351191,
	title = {Immune privilege and the philosophy of immunology},
	journal = {Front Immunol},
	volume = {5},
	year = {2014},
	month = {2014},
	pages = {110},
	issn = {1664-3224},
	doi = {10.3389/fimmu.2014.00110},
	author = {Stein-Streilein, Joan and Caspi, Rachel R}
}
@article {1363207,
	title = {Mechanisms of immune privilege in the posterior eye},
	journal = {Int Rev Immunol},
	volume = {32},
	number = {1},
	year = {2013},
	month = {2013 Feb},
	pages = {42-56},
	abstract = {Immune privilege protects vital organs and their functions from the destructive interference of inflammation. Because the eye is easily accessible for surgical manipulation and for assessing and imaging the outcomes, the eye has been a major tissue for the study of immune privilege. Here, we focus on the immune regulatory mechanisms in the posterior eye, in part, because loss of immune privilege may contribute to development of certain retinal diseases in the aging population. We begin with a background in immune privilege and then focus on the select regulatory mechanisms that have been studied in the posterior eye. The review includes a description of the immunosuppressive environment, regulatory surface molecules expressed by cells in the eye, types of cells that participate in immune regulation and finally, discusses animal models of retinal laser injury in the context of mechanisms that overcome immune privilege.},
	keywords = {Aged, Aging, Animals, Disease Models, Animal, Eye Diseases, Humans, Immune Tolerance, Posterior Eye Segment, Retinal Pigment Epithelium},
	issn = {1563-5244},
	doi = {10.3109/08830185.2012.740535},
	author = {Stein-Streilein, Joan}
}
@article {1538347,
	title = {Low dose amiodarone reduces tumor growth and angiogenesis},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Oct 22},
	pages = {18034},
	abstract = {Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone{\textquoteright}s effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug{\textquoteright}s harmful side effects.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-75142-1},
	author = {Steinberg, Eliana and Fluksman, Arnon and Zemmour, Chalom and Tischenko, Katerina and Karsch-Bluman, Adi and Brill-Karniely, Yifat and Birsner, Amy E and D{\textquoteright}Amato, Robert J and Benny, Ofra}
}
@article {1351192,
	title = {Wounding the cornea to learn how it heals},
	journal = {Exp Eye Res},
	volume = {121},
	year = {2014},
	month = {2014 Apr},
	pages = {178-93},
	abstract = {Corneal wound healing studies have a long history and rich literature that describes the data obtained over the past 70 years using many different species of animals and methods of injury. These studies have lead to reduced suffering and provided clues to treatments that are now helping patients live more productive lives. In spite of the progress made, further research is required since blindness and reduced quality of life due to corneal scarring still happens. The purpose of this review is to summarize what is known about different types of wound and animal models used to study corneal wound healing. The subject of corneal wound healing is broad and includes chemical and mechanical wound models. This review focuses on mechanical injury models involving debridement and keratectomy wounds to reflect the authors{\textquoteright} expertise.},
	keywords = {Animals, Cornea, Corneal Injuries, Debridement, Disease Models, Animal, Mice, Organ Culture Techniques, Rabbits, Wound Healing},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2014.02.007},
	author = {Stepp, Mary Ann and Zieske, James D and Trinkaus-Randall, Vickery and Kyne, Briana M and Pal-Ghosh, Sonali and Tadvalkar, Gauri and Pajoohesh-Ganji, Ahdeah}
}
@article {1319483,
	title = {Regenerating Eye Tissues to Preserve and Restore Vision},
	journal = {Cell Stem Cell},
	volume = {22},
	number = {6},
	year = {2018},
	month = {2018 Jun 01},
	pages = {834-849},
	abstract = {Ocular regenerative therapies are on track to revolutionize treatment of numerous blinding disorders, including corneal disease, cataract, glaucoma, retinitis pigmentosa, and age-related macular degeneration. A variety of transplantable products, delivered as cell suspensions or as preformed 3D structures combining cells and natural or artificial substrates, are in the pipeline. Here we review the status of clinical and preclinical studies for stem cell-based repair, covering key eye tissues from front to back, from cornea to retina, and including bioengineering approaches that advance cell product manufacturing. While recognizing the challenges, we look forward to a deep portfolio of sight-restoring, stem cell-based medicine. VIDEO ABSTRACT.},
	issn = {1875-9777},
	doi = {10.1016/j.stem.2018.05.013},
	author = {Stern, Jeffrey H and Tian, Yangzi and Funderburgh, James and Pellegrini, Graziella and Zhang, Kang and Goldberg, Jeffrey L and Ali, Robin R and Young, Michael and Xie, Yubing and Temple, Sally}
}
@article {1474217,
	title = {Subfoveal Choroidal Thickness and Associated Changes of Angiogenic Factors in Women with Severe Preeclampsia},
	journal = {Am J Perinatol},
	volume = {38},
	number = {5},
	year = {2021},
	month = {2021 Apr},
	pages = {482-489},
	abstract = {OBJECTIVE:   Severe preeclampsia complicates roughly 1\% of all pregnancies. One defining feature of severe preeclampsia is new onset visual disturbance. The accessibility of the choroid to high-resolution, noninvasive imaging makes it a reasonable target of investigation for disease prediction, stratification, or monitoring in preeclampsia. This study aimed to compare subfoveal choroidal thickness between women with severe preeclampsia and those with normotensive pregnancies, and to investigate associations between such findings and other indicators of disease severity, including gestational age and serum angiogenic factors. STUDY DESIGN:   We designed a case-control study comprised of 36 women diagnosed with severe preeclampsia (cases) matched to 37 normotensive women (controls) by race/ethnicity and parity, all diagnosed in the postpartum period. All patients underwent enhanced depth imaging spectral-domain optical coherence tomography and serum analysis. RESULTS:   Cases showed no difference in subfoveal choroidal thickness compared with controls ( = 0.65). Amongst cases, subfoveal choroidal thickness and gestational age at delivery were inversely related ( = 0.86,  \&lt; .001). There was a positive association of placental growth factor with subfoveal choroidal thickness amongst cases ( = 0.54,  = 0.002). CONCLUSION:   This study suggests a relationship between the degree of disease severity and the magnitude of choroidal thickening. We also show an association between this index and placental growth factor level in the postpartum period.},
	issn = {1098-8785},
	doi = {10.1055/s-0039-1698832},
	author = {Stern-Ascher, Conrad N and North, Victoria S and Garg, Aakriti and Ananth, Cande V and Wapner, Ronald J and Bearelly, Srilaxmi}
}
@article {1364552,
	title = {Dry eye disease: an immune-mediated ocular surface disorder},
	journal = {Arch Ophthalmol},
	volume = {130},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {90-100},
	abstract = {Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management.},
	keywords = {Adaptive Immunity, Animals, Antigen-Presenting Cells, Conjunctiva, Epithelial Cells, Humans, Immunity, Innate, Inflammation, Keratoconjunctivitis Sicca, Killer Cells, Natural, Lymphangiogenesis, T-Lymphocytes, Regulatory},
	issn = {1538-3601},
	doi = {10.1001/archophthalmol.2011.364},
	author = {Stevenson, William and Chauhan, Sunil K and Dana, Reza}
}
@article {1351193,
	title = {Effects of topical Janus kinase inhibition on ocular surface inflammation and immunity},
	journal = {Cornea},
	volume = {33},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {177-83},
	abstract = {PURPOSE: To determine the effects of topical Janus kinase inhibition on ocular surface inflammation and immunity. METHODS: Ophthalmic 0.003\% tofacitinib (CP-690,550) was administered topically to inhibit Janus kinase activation at the ocular surface. Male BALB/c mice 6 to 8 weeks of age were subjected to corneal thermocautery and randomized to receive tofacitinib, vehicle, or no treatment. Corneas were subsequently excised for fluorescence-activated cell sorting and quantitative real-time reverse transcription polymerase chain reaction. Female C57BL/6 mice 6 to 8 weeks of age were exposed to desiccating stress to induce experimental dry eye disease and randomized to receive tofacitinib, tofacitinib and vehicle, vehicle, or no treatment. Corneal fluorescein staining was performed to evaluate clinical disease severity. The corneas and conjunctivae were harvested for immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction. RESULTS: After corneal thermocautery, it was found that tofacitinib treatment decreased the corneal infiltration of CD45+, Gr-1+, and CD11b+ cells on days 1 and 3. Transcripts encoding interleukin (IL)-1β and IL-6 were significantly decreased by tofacitinib treatment at post-thermocautery day 3. In experimental dry eye disease, tofacitinib treatment twice per day significantly decreased corneal fluorescein staining on days 12 and 15. The corneal infiltration of CD11b+ cells was significantly decreased by tofacitinib treatment twice per day. Tofacitinib treatment twice per day significantly increased the corneal expression of IL-1RA, and significantly decreased the corneal expression of tumor necrosis factor and IL-23. Further, tofacitinib treatment twice per day significantly decreased the conjunctival expression of IL-17A and significantly increased the conjunctival expression of FoxP3. CONCLUSIONS: Topical ophthalmic tofacitinib, a Janus kinase inhibitor, suppressed ocular surface inflammation and immunity in experimental corneal thermocautery and dry eye disease.},
	keywords = {Adaptive Immunity, Administration, Topical, Animals, CD11b Antigen, Cell Movement, Cytokines, Disease Models, Animal, Dry Eye Syndromes, Female, Flow Cytometry, Gene Expression Regulation, Janus Kinase 3, Keratitis, Leukocyte Common Antigens, Leukocytes, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Ophthalmic Solutions, Piperidines, Protein Kinase Inhibitors, Pyrimidines, Pyrroles, Real-Time Polymerase Chain Reaction, Receptors, Chemokine},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000019},
	author = {Stevenson, William and Sadrai, Zahra and Hua, Jing and Kodati, Shilpa and Huang, Jing-Feng and Chauhan, Sunil K and Dana, Reza}
}
@article {280806,
	title = {Extraorbital lacrimal gland excision: a reproducible model of severe aqueous tear-deficient dry eye disease.},
	journal = {Cornea},
	volume = {33},
	number = {12},
	year = {2014},
	month = {2014 Dec},
	pages = {1336-41},
	abstract = {PURPOSE: The aim of this study was to establish and characterize extraorbital lacrimal gland excision (LGE) as a model of aqueous tear-deficient dry eye disease in mice. METHODS: Female C57BL/6 mice at 6 to 8 weeks of age were randomized to extraorbital LGE, sham surgery, or scopolamine groups. Mice that underwent extraorbital LGE or sham surgery were housed in the standard vivarium. Scopolamine-treated mice were housed in a controlled environment chamber that allowed for the continuous regulation of airflow (15 L/min), relative humidity (30\%), and temperature (21-23{\textdegree}C). Clinical disease severity was assessed over the course of 14 days using the phenol red thread test and corneal fluorescein staining. Real-time polymerase chain reaction was performed to assess corneal mRNA expression of interleukin 1β, tumor necrosis factor α, and matrix metalloproteinase 9. Flow cytometry was used to assess T helper cell frequencies in the conjunctivae and draining lymph nodes. RESULTS: Extraorbital LGE markedly reduced aqueous tear secretion as compared with the sham procedure and induced a more consistent decrease in aqueous tear secretion than was observed in mice that received scopolamine while housed in the controlled environment chamber. Extraorbital LGE significantly increased corneal fluorescein staining scores as compared with those of both the sham surgery and scopolamine-treated groups. Extraorbital LGE significantly increased the corneal expression of interleukin 1β, tumor necrosis factor α, and matrix metalloproteinase 9. Further, extraorbital LGE increased T helper 17-cell frequencies in the conjunctivae and draining lymph nodes. CONCLUSIONS: Extraorbital LGE induces aqueous tear-deficient dry eye disease in mice as evidenced by decreased aqueous tear secretion, increased corneal epitheliopathy, and induced ocular surface inflammation and immunity.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000264},
	author = {Stevenson, William and Chen, Yihe and Lee, Sang-Mok and Lee, Hyun Soo and Hua, Jing and Dohlman, Thomas and Shiang, Tina and Dana, Reza}
}
@article {1402589,
	title = {The Impact of Prefilled Syringes on Endophthalmitis Following Intravitreal Injection of Ranibizumab},
	journal = {Am J Ophthalmol},
	volume = {199},
	year = {2019},
	month = {2019 Mar},
	pages = {200-208},
	abstract = {PURPOSE: To compare the rates of infectious endophthalmitis following intravitreal injection of ranibizumab using prefilled syringes vs conventional preparation. DESIGN: Multicenter retrospective cohort study. METHODS: All eyes receiving intravitreal injection of 0.5\&nbsp;mg ranibizumab for retinal vascular diseases at 10 retina practices across the United States (2016 to 2017) and Japan (2009 to 2017) were included. The total numbers of eyes and injections were determined from billing codes. Endophthalmitis cases were determined from billing records and evaluated with chart review. Primary outcome was the rate of postinjection acute endophthalmitis. Secondary outcomes were visual acuity and microbial spectrum. RESULTS: A total of 243 754 intravitreal 0.5\&nbsp;mg ranibizumab injections (165 347 conventional and 78 407 prefilled) were administered to 43 132 unique patients during the study period. In the conventional ranibizumab group, a total of 43 cases of suspected endophthalmitis occurred (0.026\%; 1 in 3845 injections) and 22 cases of culture-positive endophthalmitis occurred (0.013\%; 1 in 7516 injections). In the prefilled ranibizumab group, 12 cases of suspected endophthalmitis occurred (0.015\%; 1 in 6534 injections) and 2 cases\&nbsp;of culture-positive endophthalmitis occurred (0.0026\%; 1 in 39 204 injections). Prefilled syringes were associated with a trend toward decreased risk of suspected endophthalmitis (odds ratio 0.59; 95\% confidence interval 0.31-1.12; P\&nbsp;= .10) and a statistically significant decreased risk of culture-positive endophthalmitis (odds ratio 0.19; 95\% confidence interval 0.045-0.82; P\&nbsp;= .025). Average logMAR vision loss at final follow-up was significantly worse for eyes that developed endophthalmitis from the conventional ranibizumab preparation compared to the prefilled syringe group (4.45 lines lost from baseline acuity vs 0.38 lines lost; P\&nbsp;= .0062). Oral-associated flora was found in 27.3\% (6/22) of conventional ranibizumab culture-positive endophthalmitis cases (3 cases of Streptococcus viridans, 3 cases of Enterococcus faecalis) compared to 0 cases in the prefilled ranibizumab group. CONCLUSION: In a large, multicenter, retrospective study the use of prefilled syringes during intravitreal injection of ranibizumab was associated with a reduced rate of culture-positive endophthalmitis, including from oral flora, as well as with improved visual acuity outcomes.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.11.023},
	author = {Storey, Philip P and Tauqeer, Zujaja and Yonekawa, Yoshihiro and Todorich, Bozho and Wolfe, Jeremy D and Shah, Sumit P and Shah, Ankoor R and Koto, Takashi and Abbey, Ashkan M and Morizane, Yuki and Sharma, Priya and Wood, Edward H and Morizane-Hosokawa, Mio and Pendri, Pooja and Pancholy, Maitri and Harkey, Shawn and Jeng-Miller, Karen W and Obeid, Anthony and Borkar, Durga S and Chen, Eric and Williams, Patrick and Okada, Annabelle A and Inoue, Makoto and Shiraga, Fumio and Hirakata, Akito and Shah, Chirag P and Prenner, Jonathan and Garg, Sunir and Post-Injection Endophthalmitis (PIE) Study Group}
}
@article {1302177,
	title = {Microenvironment dependent gene expression signatures in reprogrammed human colon normal and cancer cell lines},
	journal = {BMC Cancer},
	volume = {18},
	number = {1},
	year = {2018},
	month = {2018 Feb 27},
	pages = {222},
	abstract = {BACKGROUND: Since the first evidence suggesting existence of stem-like cancer cells, the process of cells reprogramming to the stem cell state remains as an attractive tool for cancer stemness research. Current knowledge in the field of cancer stemness, indicates that the microenvironment is a fundamental regulator of cell behavior. With regard to this, we investigated the changes of genome wide gene expression in reprogrammed human colon normal epithelial CRL-1831 and colon carcinoma DLD1 cell lines grown under more physiologically relevant three-dimensional (3D) cell culture microenvironment compared to 2D monolayer. METHODS: Whole genome gene expression changes were evaluated in both cell lines cultured under 3D conditions over a 2D monolayer by gene expression microarray analysis. To evaluate the biological significance of gene expression changes, we performed pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene network analysis was used to study relationships between differentially expressed genes (DEGs) in functional categories by the GeneMANIA Cytoscape toolkit. RESULTS: In total, we identified 3228 and 2654 differentially expressed genes (DEGs) for colon normal and cancer reprogrammed cell lines, respectively. Furthermore, the expression of 1097 genes was commonly regulated in both cell lines. KEGG enrichment analysis revealed that in total 129 and 101 pathways for iPSC-CRL-1831 and for CSC-DLD1, respectively, were enriched. Next, we grouped these pathways into three functional categories: cancer transformation/metastasis, cell interaction, and stemness. β-catenin (CTNNB1) was confirmed as a hub gene of all three functional categories. CONCLUSIONS: Our present findings suggest common pathways between reprogrammed human colon normal epithelium (iPSC-CRL-1831) and adenocarcinoma (CSC-DLD1) cells grown under 3D microenvironment. In addition, we demonstrated that pathways important for cancer transformation and tumor metastatic activity are altered both in normal and cancer stem-like cells during the transfer from 2D to 3D culture conditions. Thus, we indicate the potential of cell culture models enriched in normal and cancer stem-like cells for the identification of new therapeutic targets in cancer treatment.},
	issn = {1471-2407},
	doi = {10.1186/s12885-018-4145-8},
	author = {Strainiene, Egle and Binkis, Mindaugas and Urnikyte, Silvija and Stankevicius, Vaidotas and Sasnauskiene, Ausra and Kundrotas, Gabrielis and Kazlauskas, Andrius and Suziedelis, Kestutis}
}
@article {1328905,
	title = {The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)},
	journal = {Ophthalmic Res},
	year = {2018},
	month = {2018 Aug 15},
	pages = {1-10},
	abstract = {BACKGROUND/AIMS: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. METHODS: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. RESULTS: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5\%) had areas of DDAF with an average lesion area of 3.2 {\textpm} 3.5 mm2 (range 0.36-10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 {\textpm} 5.8 dB. CONCLUSIONS: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.},
	issn = {1423-0259},
	doi = {10.1159/000491791},
	author = {Strauss, Rupert W and Mu{\~n}oz, Beatriz and Ahmed, Mohamed I and Bittencourt, Millena and Sch{\"o}nbach, Etienne M and Michaelides, Michel and Birch, David and Zrenner, Eberhart and Ervin, Ann-Margret and Charbel Issa, Peter and Kong, Jun and Wolfson, Yulia and Shah, Mahmood and Bagheri, Saghar and West, Sheila and Scholl, Hendrik P N and for~the~ProgStar-4~Study~Group}
}
@article {1319484,
	title = {Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) Study: Design and Baseline Characteristics (Report No. 1)},
	journal = {Ophthalmic Res},
	volume = {61},
	number = {1},
	year = {2019},
	month = {2019},
	pages = {36-43},
	abstract = {PURPOSE: To describe the study design and characteristics at first visit of participants in the longitudinal Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study. METHODS: Scotopic microperimetry (sMP) was performed in one designated study eye in a subset of participants with molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a multicenter natural history study (ProgStar). Study visits were every 6 months over a period ranging from 6 to 24 months, and also included fundus autofluorescence (FAF). RESULTS: SMART enrolled 118 participants (118 eyes). At the first visit of SMART, the mean sensitivity in mesopic microperimetry was 11.48 ({\textpm}5.05; range 0.00-19.88) dB and in sMP 11.25 ({\textpm}5.26; 0-19.25) dB. For FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62 [{\textpm}3.48; 0.10-21.46] mm2), and a total of 76 eyes (65.5\%) had a lesion of definitely decreased autofluorescence with a mean lesion size of 3.46 ({\textpm}3.60; 0.21-21.46) mm2. CONCLUSIONS: Rod function is impaired in STGD1 and can be assessed by sMP. Testing rod function may serve as a potential outcome measure for future clinical treatment trials. This is evaluated in the SMART study.},
	issn = {1423-0259},
	doi = {10.1159/000488711},
	author = {Strauss, Rupert W and Kong, Xiangrong and Bittencourt, Millena G and Ho, Alexander and Jha, Anamika and Sch{\"o}nbach, Etienne M and Ahmed, Mohamed I and Mu{\~n}oz, Beatriz and Ervin, Ann-Margret and Michaelides, Michel and Birch, David G and Sahel, Jos{\'e}-Alain and Sunness, Janet S and Zrenner, Eberhart and Bagheri, Saghar and Ip, Michael and Sadda, SriniVas and West, Sheila and Scholl, Hendrik P N and for~the~SMART~Study~Group}
}
@article {1307462,
	title = {Genomic loci modulating retinal ganglion cell death following elevated IOP in the mouse},
	journal = {Exp Eye Res},
	volume = {169},
	year = {2018},
	month = {2018 Apr},
	pages = {61-67},
	abstract = {The present study was designed to identify genomic loci modulating the susceptibility of retinal ganglion cells (RGC) to elevated intraocular pressure (IOP) in the BXD recombinant inbred mouse strain set. IOP was elevated by injecting magnetic microspheres into the anterior chamber and blocking the trabecular meshwork using a handheld magnet to impede drainage. The IOP was then measured over the next 21 days. Only animals with IOP greater than 25 mmHg for two consecutive days or an IOP above 30 mmHg on a single day after microsphere-injection were used in this study. On day 21, mice were sacrificed and the optic nerve was processed for histology. Axons were counted for both the injected and the control eye in 49 BXD strains, totaling 181 normal counts and 191 counts associated with elevated IOP. The axon loss for each strain was calculated and the data were entered into genenetwork.org. The average number of normal axons in the optic nerve across all strains was 54,788 {\textpm} 16\% (SD), which dropped to 49,545 {\textpm} 20\% in animals with artificially elevated IOP. Interval mapping demonstrated a relatively similar genome-wide map for both conditions with a suggestive Quantitative Trait Locus (QTL) on proximal Chromosome 3. When the relative axon loss was used to generate a genome-wide interval map, we identified one significant QTL (p ,
	issn = {1096-0007},
	doi = {10.1016/j.exer.2017.12.013},
	author = {Struebing, Felix L and King, Rebecca and Li, Ying and Cooke Bailey, Jessica N and Wiggs, Janey L and Geisert, Eldon E}
}
@article {630201,
	title = {Proliferative Hypertensive Retinopathy.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {3},
	year = {2016},
	month = {2016 Mar 1},
	pages = {345-6},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.5583},
	author = {Stryjewski, Tomasz P and Papakostas, Thanos D and Vavvas, Demetrios}
}
@article {1363208,
	title = {Genetic correlates of proliferative vitreoretinopathy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {3},
	year = {2013},
	month = {2013 Mar 05},
	keywords = {Class Ib Phosphatidylinositol 3-Kinase, Europe, Female, Gene Frequency, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Receptors, Tumor Necrosis Factor, Type II, Research Design, Retinal Detachment, Smad7 Protein, Tumor Necrosis Factor-alpha, Vitreoretinopathy, Proliferative},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-11508},
	author = {Stryjewski, Tomasz P and Vavvas, Demetrios G}
}
@article {688661,
	title = {Multimodal Imaging of Elschnig Spots: A Case of Simultaneous Hypertensive Retinopathy, Choroidopathy, and Neuropathy.},
	journal = {Semin Ophthalmol},
	year = {2016},
	month = {2016 Apr 15},
	pages = {1-3},
	abstract = {A 65-year-old woman with chronic hypertension, chronic renal insufficiency, and schizophrenia self-discontinued her medications and presented complaining of decreased vision; she was found to have a blood pressure of 256/156 and visual acuity 20/70 OD. In the emergency department, her blood pressure was rapidly lowered to a nadir of 134/104. During the course of her hospitalization, her visual acuity declined from 20/70 to 20/200 OD in parallel with a decline in her renal function. Multi-modal imaging revealed simultaneous hypertensive retinopathy, choroidopathy, and optic neuropathy. Autofluorescence can play an important role in the diagnosis of hypertensive choroidopathy.},
	issn = {1744-5205},
	doi = {10.3109/08820538.2015.1115091},
	author = {Stryjewski, Tomasz P and Papakostas, Thanos D and Eliott, Dean}
}
@article {1732566,
	title = {Towards modifying the genetic predisposition for glaucoma: An overview of the contribution and interaction of genetic and environmental factors},
	journal = {Mol Aspects Med},
	volume = {93},
	year = {2023},
	month = {2023 Jul 07},
	pages = {101203},
	abstract = {Glaucoma, the leading cause of irreversible blindness worldwide, is a complex human disease, with both genetic and environmental determinants. The availability of large-scale, population-based cohorts and biobanks, combining genotyping and detailed phenotyping, has greatly accelerated research into the aetiology of glaucoma in recent years. Hypothesis-free genome-wide association studies have furthered our understanding of the complex genetic architecture underpinning the disease, while epidemiological studies have provided advances in the identification and characterisation of environmental risk factors. It is increasingly recognised that the combined effects of genetic and environmental factors may confer a disease risk that reflects a departure from the simple additive effect of the two. These gene-environment interactions have been implicated in a host of complex human diseases, including glaucoma, and have several important diagnostic and therapeutic implications for future clinical practice. Importantly, the ability to modify the risk associated with a particular genetic makeup promises to lead to personalised recommendations for glaucoma prevention, as well as novel treatment approaches in years to come. Here we provide an overview of genetic and environmental risk factors for glaucoma, as well as reviewing the evidence and discussing the implications of gene-environment interactions for the disease.},
	issn = {1872-9452},
	doi = {10.1016/j.mam.2023.101203},
	author = {Stuart, Kelsey V and Pasquale, Louis R and Kang, Jae H and Foster, Paul J and Khawaja, Anthony P}
}
@article {1662327,
	title = {The association of alcohol consumption with glaucoma and related traits: findings from the UK Biobank},
	journal = {Ophthalmol Glaucoma},
	year = {2022},
	author = {Stuart, KV and Luben, R N and Warwick, AN and Madjedi, KM and Patel, PJ and Biradar, MI and Sun, Z and Chia, MA and Pasquale, L. R. and Wiggs, J L and Kang, J H and Kim, J. and Aschard, H and Tran, JH and Lentjes, MAH and Foster, PJ and Khawaja, AP and Modifiable Risk Factors for Glaucoma Collaboration, the UK Biobank Eye and Vision Consortium, and the International Glaucoma Gen}
}
@article {1645460,
	title = {Alcohol, Intraocular Pressure, and Open-Angle Glaucoma: A Systematic Review and Meta-analysis},
	journal = {Ophthalmology},
	volume = {129},
	number = {6},
	year = {2022},
	month = {2022 06},
	pages = {637-652},
	abstract = {TOPIC: This systematic review and meta-analysis summarizes the existing evidence for the association of alcohol use with intraocular pressure (IOP) and open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding and quantifying these associations may aid clinical guidelines or treatment strategies and shed light on disease pathogenesis. The role of alcohol, a modifiable factor, in determining IOP and OAG risk also may be of interest from an individual or public health perspective. METHODS: The study protocol was preregistered in the Open Science Framework Registries (https://osf.io/z7yeg). Eligible articles (as of May 14, 2021) from 3 databases (PubMed, Embase, Scopus) were independently screened and quality assessed by 2 reviewers. All case-control, cross-sectional, and cohort studies reporting a quantitative effect estimate and 95\% confidence interval (CI) for the association between alcohol use and either IOP or OAG were included. The evidence for the associations with both IOP and OAG was qualitatively summarized. Effect estimates for the association with OAG were pooled using random effects meta-analysis. Studies not meeting formal inclusion criteria for systematic review, but with pertinent results, were also appraised and discussed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Thirty-four studies were included in the systematic review. Evidence from 10 studies reporting an association with IOP suggests that habitual alcohol use is associated with higher IOP and prevalence of ocular hypertension (IOP \&gt; 21 mmHg), although absolute effect sizes were small. Eleven of 26 studies, comprising 173 058 participants, that tested for an association with OAG met inclusion criteria for meta-analysis. Pooled effect estimates indicated a positive association between any use of alcohol and OAG (1.18; 95\% confidence interval [CI], 1.02-1.36; P\&nbsp;= 0.03; I2\&nbsp;= 40.5\%), with similar estimates for both prevalent and incident OAG. The overall GRADE certainty of evidence was very low. CONCLUSIONS: Although this meta-analysis suggests a harmful association between alcohol use and OAG, our results should be interpreted cautiously given the weakness and heterogeneity of the underlying evidence base, the small absolute effect size, and the borderline statistical significance. Nonetheless, these findings may be clinically relevant, and future research should focus on improving the quality of evidence.},
	keywords = {Cross-Sectional Studies, Ethanol, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Ocular Hypertension, Tonometry, Ocular},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.01.023},
	author = {Stuart, Kelsey V and Madjedi, Kian and Luben, Robert N and Chua, Sharon Y L and Warwick, Alasdair N and Chia, Mark and Pasquale, Louis R and Wiggs, Janey L and Kang, Jae H and Hysi, Pirro G and Tran, Jessica H and Foster, Paul J and Khawaja, Anthony P and Modifiable Risk Factors for Glaucoma Collaboration}
}
@article {1580503,
	title = {Atypical spatiotemporal activation of cerebellar lobules during emotional face processing in adolescents with autism},
	journal = {Hum Brain Mapp},
	volume = {42},
	number = {7},
	year = {2021},
	month = {2021 May},
	pages = {2099-2114},
	abstract = {Autism spectrum disorder (ASD) is characterized by social deficits and atypical facial processing of emotional expressions. The underlying neuropathology of these abnormalities is still unclear. Recent studies implicate cerebellum in emotional processing; other studies show cerebellar abnormalities in ASD. Here, we elucidate the spatiotemporal activation of cerebellar lobules in ASD during emotional processing of happy and angry faces in adolescents with ASD and typically developing (TD) controls. Using magnetoencephalography, we calculated dynamic statistical parametric maps across a period of 500 ms after emotional stimuli onset and determined differences between group activity to happy and angry emotions. Following happy face presentation, adolescents with ASD exhibited only left-hemispheric cerebellar activation in a cluster extending from lobule VI to lobule V (compared to TD controls). Following angry face presentation, adolescents with ASD exhibited only midline cerebellar activation (posterior IX vermis). Our findings indicate an early (125-175 ms) overactivation in cerebellar activity only for happy faces and a later overactivation for both happy (250-450 ms) and angry (250-350 ms) faces in adolescents with ASD. The prioritized hemispheric activity (happy faces) could reflect the promotion of a more flexible and adaptive social behavior, while the latter midline activity (angry faces) may guide conforming behavior.},
	issn = {1097-0193},
	doi = {10.1002/hbm.25349},
	author = {Styliadis, Charis and Leung, Rachel and {\"O}zcan, Selin and Moulton, Eric A and Pang, Elizabeth and Taylor, Margot J and Papadelis, Christos}
}
@article {1629449,
	title = {Gray matter volume alterations in patients with strabismus and amblyopia: voxel-based morphometry study},
	journal = {Sci Rep},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 Jan 10},
	pages = {458},
	abstract = {This study proposes the use of the voxel-based morphometry (VBM) technique to investigate structural alterations of the cerebral cortex in patients with strabismus and amblyopia (SA). Sixteen patients with SA and sixteen healthy controls (HCs) underwent magnetic resonance imaging. Original whole brain images were analyzed using the VBM method. Pearson correlation analysis was performed to evaluate the relationship between mean gray matter volume (GMV) and clinical manifestations. Receiver operating characteristic (ROC) curve analysis was applied to classify the mean GMV values of the SA group and HCs. Compared with the HCs, GMV values in the SA group showed a significant difference in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, bilateral parahippocampal gyrus, and left anterior cingulate cortex. The mean GMV value in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, and bilateral parahippocampal gyrus were negatively correlated with the angle of strabismus. The ROC curve analysis of each cerebral region confirmed the accuracy of the area under the curve. Patients with SA have reduced GMV values in some brain regions. These findings might help to reveal the potential pathogenesis of SA and its relationship with the atrophy of specific regions of the brain.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-04184-w},
	author = {Su, Ting and Zhu, Pei-Wen and Li, Biao and Shi, Wen-Qing and Lin, Qi and Yuan, Qing and Jiang, Nan and Pei, Chong-Gang and Shao, Yi}
}
@article {913531,
	title = {IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity.},
	journal = {J Immunol},
	volume = {197},
	number = {9},
	year = {2016},
	month = {2016 Nov 01},
	pages = {3464-3470},
	abstract = {Accumulating evidence shows that IL-17 is critically involved in diverse autoimmune diseases. However, its effect on the induction and progression of the humoral immune response is not fully understood. Using a preclinical model of IL-17-mediated dry eye disease, we demonstrate that upon encountering both the BCR and a secondary T cell signal, IL-17 can enhance B cell proliferation and germinal center formation in dry eye disease mice, suggesting that a stable Ag-dependent T-B cell interaction is required. Additionally, IL-17 also promotes the differentiation of B cells into isotype-switched B cells and plasma cells. Furthermore, we show that Th17 cells are more effective than Th1 cells to provide B cell help. Reduced B cell response correlates with significant reduction in clinical disease after in vivo IL-17A neutralization. In conclusion, our findings demonstrate a new role of IL-17 in promoting autoimmunity in part through directly enhancing B cell proliferation, differentiation, and plasma cell generation.},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1502641},
	author = {Subbarayal, Brinda and Chauhan, Sunil K and Di Zazzo, Antonio and Dana, Reza}
}
@article {1538339,
	title = {Making the decision to donate eyes: Perspectives from the families of the deceased in Madurai, India},
	journal = {Indian J Ophthalmol},
	volume = {68},
	number = {10},
	year = {2020},
	month = {2020 Oct},
	pages = {2094-2098},
	abstract = {Purpose: To identify factors affecting family members{\textquoteright} decision whether to donate eye organs. Methods: A community-based case-control study based on in-home interviews with families of deceased individuals who had or had not donated eye organs, in Madurai district, Tamil Nadu, India. Data collected were knowledge and awareness of eye donations, whether the deceased individual had expressed or pledged willingness to donate, and family members{\textquoteright} attitudes and willingness to donate their own eye organs. Results: Seventy-six families of donors and 256 families of non-donors completed the survey. Multivariable analysis showed that the following variables were significantly associated with a donation: age, whether the deceased had registered for eye donation, pre-expressed willingness of deceased to donate, whether family members personally know beneficiaries of eye donations, and higher score on a scale evaluating knowledge and awareness about eye donation. The majority of donors{\textquoteright} families (71\%) had been encouraged by someone to donate. Among non-donor families, a substantially larger fraction (52.8\%) indicated they would have donated had someone reminded or encouraged them to do so, in comparison with those who indicated lack of awareness or knowledge (14.5\%). Conclusion: Community programs are likely to be effective if they encourage individuals to pledge their eyes or express their willingness to donate their eyes to family members in advance of death; they increase public awareness of the value of eye donation. A friend, family member, neighbor or counselor approaching bereaved families and having a dialogue about eye donation would substantially increase the probability of a decision to donate.},
	issn = {1998-3689},
	doi = {10.4103/ijo.IJO_2324_19},
	author = {Subburaman, Ganesh-Babu B and Kempen, John H and Durairaj, Saravanan and Balakrishnan, Vijayakumar and Valaguru, Vijayakumar and Namperumalsamy, Venkatesh Prajna and Thulasiraj, Ravilla Duraisamy and Gupta, Sachin}
}
@article {1589766,
	title = {Response to comments: Making the decision to donate eye organs: Perspectives from the families of the deceased in Madurai, India},
	journal = {Indian J Ophthalmol},
	volume = {69},
	number = {4},
	year = {2021},
	month = {2021 Apr},
	pages = {1020-1021},
	issn = {1998-3689},
	doi = {10.4103/ijo.IJO_3234_20},
	author = {Subburaman, Ganesh-Babu B and Kempen, John H and Duraisamy, Saravanan and Vijayakumar, Balakrishnan and Valaguru, Vijayakumar and Namperumalsamy, Venkatesh Prajna and Ravilla, Thulasiraj D and Gupta, Sachin}
}
@article {1466904,
	title = {Filling Adeno-Associated Virus Capsids: Estimating Success by Cryo-Electron Microscopy},
	journal = {Hum Gene Ther},
	volume = {30},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {1449-1460},
	abstract = {Adeno-associated viruses (AAVs) have been employed successfully as gene therapy vectors in treating various genetic diseases for almost two decades. However, transgene packaging is usually imperfect, and developing a rapid and accurate method for measuring the proportion of DNA encapsidation is an important step for improving the downstream process of large scale vector production. In this study, we used two-dimensional class averages and three-dimensional classes, intermediate outputs in the single particle cryo-electron microscopy (cryo-EM) image reconstruction pipeline, to determine the proportion of DNA-packaged and empty capsid populations. Two different preparations of AAV3 were analyzed to estimate the minimum number of particles required to be sampled by cryo-EM in order for robust calculation of the proportion of the full versus empty capsids in any given sample. Cost analysis applied to the minimum amount of data required for a valid ratio suggests that cryo-EM is an effective approach to analyze vector preparations.},
	issn = {1557-7422},
	doi = {10.1089/hum.2019.041},
	author = {Subramanian, Suriyasri and Maurer, Anna C and Bator, Carol M and Makhov, Alexander M and Conway, James F and Turner, Kevin B and Marden, James H and Vandenberghe, Luk H and Hafenstein, Susan L}
}
@article {1589737,
	title = {Impact of COVID-19 pandemic on ophthalmology medical student teaching: educational innovations, challenges, and future directions},
	journal = {Surv Ophthalmol},
	volume = {67},
	number = {1},
	year = {2022},
	month = {2022 Jan-Feb},
	pages = {217-225},
	abstract = {Graduate medical education (GME) in ophthalmology has faced and overcome many challenges over the past years, and 2020 has been a game-changer. Although the severe acute respiratory syndrome coronavirus pandemic disrupted medical education globally, ophthalmic educators rapidly transformed their curricula to novel and effective virtual learning formats. Thus, while the COVID-19 outbreak has been one of the most significant challenges faced in the history of medical education, it has also provided an impetus to develop innovative teaching practices, bringing with it unprecedented success in allowing medical students to continue their education in ophthalmology despite these challenges. We review and appraise novel educational interventions implemented by various institutions in response to the COVID-19 pandemic, highlighting their effectiveness, challenges and proposing future directions beyond the pandemic. Many of these innovations will persist even after the end of the pandemic because they have proven that face-to-face learning is not required for all aspects of the ophthalmic GME curriculum. As ophthalmic educators harness the power of educational technology it is critical that their novel educational initiatives are incorporated into competency-based curricula with assessments mapped to the competencies. Future research should focus on evaluating the impact of this transformation to virtual learning environments on student performances as well as implementing longitudinal assessment strategies for clinical competence in workplace-based practice.},
	keywords = {COVID-19, Curriculum, Education, Medical, Humans, Ophthalmology, Pandemics, SARS-CoV-2, Students, Medical},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2021.03.011},
	author = {Succar, Tony and Beaver, Hilary A and Lee, Andrew G}
}
@article {1460362,
	title = {ADVANCING OPHTHALMOLOGY MEDICAL STUDENT EDUCATION: INTERNATIONAL INSIGHTS AND STRATEGIES FOR ENHANCED TEACHING},
	journal = {Surv Ophthalmol},
	year = {2019},
	month = {2019 Aug 28},
	abstract = {Enhancing medical student education in ophthalmology can lead to improved eye health care delivery and patient outcomes across all primary care and specialty disciplines., There has been a resurgence in interest in delivering high quality ophthalmic medical student education. This educational revival is both timely and topical. A general consensus has emerged that ,rather than focusing solely on increasing teaching time, strategies are needed to focus on how to optimize the limited time allotted to ophthalmology. All physicians should be prepared to provide competent and confident ophthalmic care based upon exciting innovations in ophthalmic curricula content, teaching methodologies, instructional design, learning objectives and assessment methods. We provide an update on new and innovative ophthalmic teaching and learning practices. We critically appraise and summarize novel educational strategies from around the world that can be universally applicable in enhancing ophthalmology teaching in medical school curricula. It is our hope that, while there is marginalization of ophthalmology training, these strategies can be used to further improve teaching and learning in the limited time available in medical curricula and provide an impetus for further research and innovations in teaching ophthalmology to medical students.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2019.08.006},
	author = {Succar, Tony and Grigg, John and Beaver, Hilary A and Lee, Andrew G}
}
@article {1532340,
	title = {Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update},
	journal = {Indian J Ophthalmol},
	volume = {68},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {1787-1798},
	abstract = {Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.},
	issn = {1998-3689},
	doi = {10.4103/ijo.IJO_1248_20},
	author = {Sudharshan, Sridharan and Nair, Nivedita and Curi, Andre and Banker, Alay and Kempen, John H}
}
@article {1351194,
	title = {Anterior chamber intraocular lens implantation in patients with a history of chronic uveitis: five-year follow-up},
	journal = {J Cataract Refract Surg},
	volume = {40},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {77-81},
	abstract = {PURPOSE: To compare the incidence of long-term complications after cataract surgery with primary anterior chamber intraocular lens (AC IOL) implantation in uveitic patients and patients without a history of intraocular inflammation (control group). SETTING: Single-center private practice. DESIGN: Retrospective clinical study. METHODS: The study comprised patients who between November 2005 and August 2010 had cataract extraction followed by AC IOL implantation because conventional placement was not possible. Outcome measures were the incidence of intraoperative and postoperative complications, preoperative corrected distance visual acuity (CDVA), and CDVA after 1 year. RESULTS: Of the 39 patients identified through electronic medical records, 17 (17 eyes) had a history of chronic uveitis and 22 (23 eyes) had no intraocular inflammatory disease. There were no significant differences in the incidence of intraoperative and postoperative complications between the 2 groups during follow-up (range 12 to 68 months) (P=.702). Although uveitic eyes had a greater risk for epiretinal membrane formation, the incidence of uveitis flareups attributed to the IOL and deposits on IOL surfaces was comparable to that in the control group (P\&lt;.001). The CDVA improved significantly in both groups 1 year after surgery (P\&lt;.01 and P\&lt;.001, respectively). CONCLUSION: In uveitic eyes with inadequate capsule support, AC IOL implantation restored visual function without a significant increase in long-term postoperative complications compared with eyes that had no history of uveitis.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Anterior Chamber, Chronic Disease, Female, Follow-Up Studies, Humans, Incidence, Lens Implantation, Intraocular, Male, Middle Aged, Postoperative Complications, Pseudophakia, Uveitis, Visual Acuity, Young Adult},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2013.06.024},
	author = {Suelves, Ana M and Siddique, Sana S and Schurko, Brian and Foster, C Stephen}
}
@article {705131,
	title = {Nuclear cataract as an early predictive factor for recalcitrant juvenile idiopathic arthritis-associated uveitis.},
	journal = {J AAPOS},
	volume = {20},
	number = {3},
	year = {2016},
	month = {2016 Jun},
	pages = {232-238.e1},
	abstract = {PURPOSE: To analyze factors predictive of having treatment-resistant uveitis in patients with juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: The medical records of patients diagnosed with JIA-associated uveitis treated at a single tertiary referral center from October 2005 to March 2013 were reviewed retrospectively. The main outcome measures were demographic characteristics, ocular comorbidity, clinical course, treatments, and baseline risk factors associated with poor response to first-line therapies. RESULTS: A total of 96 patients (175 eyes) were included. Of these, 58 patients (108 eyes) required biologic disease-modifying antirheumatic drugs or alkylating agents for their uveitis during follow-up (recalcitrant group), and 38 patients (67 eyes) did not (nonrecalcitrant group). Eyes of the recalcitrant group tended to have a higher incidence of cataract at baseline (49\%; P\&nbsp;\&lt;\&nbsp;0.0001). In the nonrecalcitrant group, the most frequent complications were cataract (20.9\%) and secondary glaucoma (20.9\%). The mean number of flares in the recalcitrant group was significantly reduced from 3.7/eye/year prior to cataract surgery to 1.6/eye/year after (P\&nbsp;\&lt;\&nbsp;0.0001). Nuclear cataract was found to be an independent predictor for a severe course of JIA-associated uveitis. Any other type of cataract, posterior synechiae, male sex, or active uveitis at baseline were not found to be independently associated with recalcitrant uveitis. CONCLUSIONS: Nuclear cataract at baseline evaluation is a risk factor for poor response to first-line therapies in JIA-associated uveitis patients.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2016.02.010},
	author = {Suelves, Ana M and Lamba, Neerav and Meese, Halea K and Foster, C Stephen and Gonz{\'a}lez-Mart{\'\i}n, Jesus Maria and D{\'\i}az-Llopis, Manuel and Christen, William G}
}
@article {1363209,
	title = {Increased resistance to Staphylococcus aureus endophthalmitis in BALB/c mice: Fas ligand is required for resolution of inflammation but not for bacterial clearance},
	journal = {Infect Immun},
	volume = {81},
	number = {6},
	year = {2013},
	month = {2013 Jun},
	pages = {2217-25},
	abstract = {FasL was recently shown be required for bacterial clearance in C57BL/6 mice that express the FasL.1 allotype. The FasL.2 allotype is expressed in BALB/c mice and exhibits increased binding affinity to and increased cytotoxic activity against Fas(+) target cells. Therefore, we hypothesized that BALB/c mice would be more resistant to Staphylococcus aureus-induced endophthalmitis. To test this hypothesis, C57BL/6, BALB/c, and BALB(gld) mice received intravitreal injections of 2,500 CFU of S. aureus (RN6390). Clinical examinations, electroretinography (ERG), histology, and bacterial quantification were performed at 24, 48, 72, and 96 h postinjection. The myeloperoxidase (MPO) assay was used to quantitate neutrophil infiltration. At 96 h postinfection, 86\% of C57BL/6 mice presented with complete destruction of the eye, compared to only 29\% of BALB/c mice with complete destruction. To our surprise, in the absence of Fas ligand, BALB(gld) mice showed no difference in bacterial clearance compared to BALB/c mice. However, histology and ERG analysis revealed increased retinal damage and significant loss of retinal function. MPO analysis revealed equal numbers of neutrophils in BALB(gld) and BALB/c mice at 24 h postinfection. However, at 48 h, the neutrophil numbers remained significantly elevated in BALB(gld) mice, correlating with the increased retinal damage observed in BALB(gld) mice. We conclude that the increased resistance to S. aureus induced endophthalmitis in BALB/c mice is not dependent upon the FasL. However, in contrast to C57BL/6 mice, FasL is required for resolution of inflammation and protecting host tissue from nonspecific damage in BALB/c mice.},
	keywords = {Animals, Endophthalmitis, Fas Ligand Protein, Female, Genetic Predisposition to Disease, Inflammation, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Peroxidase, Retina, Staphylococcal Infections, Staphylococcus aureus},
	issn = {1098-5522},
	doi = {10.1128/IAI.00405-12},
	author = {Sugi, Norito and Whiston, Emily A and Ksander, Bruce R and Gregory, Meredith S}
}
@article {1417578,
	title = {How to choose and conduct a research project: some advice for young investigators},
	journal = {Arq Bras Oftalmol},
	volume = {82},
	number = {1},
	year = {2019},
	month = {2019 Jan-Feb},
	pages = {1},
	issn = {1678-2925},
	doi = {10.5935/0004-2749.20190006},
	author = {Sullivan, David A}
}
@article {1125396,
	title = {TFOS DEWS II Sex, Gender, and Hormones Report},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {284-333},
	abstract = {One of the most compelling features of dry eye disease (DED) is that it occurs more frequently in women than men. In fact, the female sex is a significant risk factor for the development of DED. This sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (e.g. androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (e.g. microRNAs). In addition to sex, gender also appears to be a risk factor for DED. "Gender" and "sex" are words that are often used interchangeably, but they have distinct meanings. "Gender" refers to a person{\textquoteright}s self-representation as a man or woman, whereas "sex" distinguishes males and females based on their biological characteristics. Both gender and sex affect DED risk, presentation of the disease, immune responses, pain, care-seeking behaviors, service utilization, and myriad other facets of eye health. Overall, sex, gender and hormones play a major role in the regulation of ocular surface and adnexal tissues, and in the difference in DED prevalence between women and men. The purpose of this Subcommittee report is to review and critique the nature of this role, as well as to recommend areas for future research to advance our understanding of the interrelationships between sex, gender, hormones and DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.04.001},
	author = {Sullivan, David A and Rocha, Eduardo M and Aragona, Pasquale and Clayton, Janine A and Ding, Juan and Golebiowski, Blanka and Hampel, Ulrike and McDermott, Alison M and Schaumberg, Debra A and Srinivasan, Sruthi and Versura, Piera and Willcox, Mark D P}
}
@article {1351195,
	title = {Serum-induced differentiation of human meibomian gland epithelial cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {6},
	year = {2014},
	month = {2014 May 27},
	pages = {3866-77},
	abstract = {PURPOSE: We hypothesize that culturing immortalized human meibomian gland epithelial cells in serum-containing medium will induce their differentiation. The purpose of this investigation was to begin to test our hypothesis, and explore the impact of serum on gene expression and lipid accumulation in human meibomian gland epithelial cells. METHODS: Immortalized and primary human meibomian gland epithelial cells were cultured in the presence or absence of serum. Cells were evaluated for lysosome and lipid accumulation, polar and neutral lipid profiles, and gene expression. RESULTS: Our results support our hypothesis that serum stimulates the differentiation of human meibomian gland epithelial cells. This serum-induced effect is associated with a significant increase in the expression of genes linked to cell differentiation, epithelium development, the endoplasmic reticulum, Golgi apparatus, vesicles, and lysosomes, and a significant decrease in gene activity related to the cell cycle, mitochondria, ribosomes, and translation. These cellular responses are accompanied by an accumulation of lipids within lysosomes, as well as alterations in the fatty acid content of polar and nonpolar lipids. Of particular importance, our results show that the molecular and biochemical changes of immortalized human meibomian gland epithelial cells during differentiation are analogous to those of primary cells. CONCLUSIONS: Overall, our findings indicate that immortalized human meibomian gland epithelial cells may serve as an ideal preclinical model to identify factors that control cellular differentiation in the meibomian gland.},
	keywords = {Cell Differentiation, Cells, Cultured, Epithelial Cells, Eye Proteins, Gene Expression Regulation, Humans, Lipid Metabolism, Lysosomes, Meibomian Glands, Real-Time Polymerase Chain Reaction, RNA, Messenger, Serum},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-13407},
	author = {Sullivan, David A and Liu, Yang and Kam, Wendy R and Ding, Juan and Green, Karin M and Shaffer, Scott A and Hatton, Mark P and Liu, Shaohui}
}
@article {1263416,
	title = {The scientific dry eye disease journey: From the beginning to the end of the beginning},
	journal = {Cont Lens Anterior Eye},
	volume = {41},
	number = {1},
	year = {2018},
	month = {2018 Feb},
	pages = {1-4},
	issn = {1476-5411},
	doi = {10.1016/j.clae.2017.11.001},
	author = {Sullivan, David A}
}
@article {1309964,
	title = {Meibomian Gland Dysfunction in Primary and Secondary Sj{\"o}gren Syndrome},
	journal = {Ophthalmic Res},
	year = {2018},
	month = {2018 Apr 06},
	abstract = {PURPOSE: We hypothesized that women with primary (pSS) and secondary Sj{\"o}gren syndrome (sSS; with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]) have meibomian gland dysfunction (MGD). We sought to test our hypothesis.

METHODS: Subjects with pSS, sSS + SLE, sSS + RA, and non-SS-related MGD were recruited from the Sj{\"o}gren{\textquoteright}s Syndrome Foundation or outpatient clinics at Tufts University School of Dental Medicine or Brigham and Women{\textquoteright}s Hospital. The control population was recruited from the Greater Boston area. After providing written informed consent, the subjects underwent an eye examination and/or completed two questionnaires that assess symptoms of dry eye disease (DED).

RESULTS: Our results demonstrate that pSS and sSS patients have MGD. These subjects had meibomian gland orifice metaplasia, an increased number of occluded meibomian gland orifices, and a reduced quality of meibomian gland secretions. Further, patients with pSS, sSS + SLE, sSS + RA, and MGD had significant alterations in their tear film, lid margin, cornea, and conjunctiva. Symptoms of DED were increased \~{}10-fold in all pSS, sSS, and MGD groups relative to controls.

CONCLUSIONS: Our findings support our hypothesis and show that individuals with pSS, sSS + SLE, and sSS + RA have MGD. In addition, our study indicates that patients with pSS and sSS have both aqueous-deficient and evaporative DED.},
	issn = {1423-0259},
	doi = {10.1159/000487487},
	author = {Sullivan, David A and Dana, Reza and Sullivan, Rose M and Krenzer, Kathleen L and Sahin, Afsun and Arica, Beril and Liu, Yang and Kam, Wendy R and Papas, Athena S and Cermak, Jennifer M}
}
@article {1364553,
	title = {Report of the TFOS/ARVO Symposium on global treatments for dry eye disease: an unmet need},
	journal = {Ocul Surf},
	volume = {10},
	number = {2},
	year = {2012},
	month = {2012 Apr},
	pages = {108-16},
	abstract = {In September 2010, a Symposium in Florence, Italy, was held to address the unmet need for global treatments for dry eye disease (DED). It was sponsored by The Tear Film \&amp; Ocular Surface Society (TFOS; www.TearFilm.org) and co-sponsored by the Association for Research in Vision \&amp; Ophthalmology (www.arvo.org). The Symposium objectives were two-fold: first, to discuss accepted and emerging clinical endpoints of DED with regulatory experts from around the world; and second, to consider how to improve clinical trials of treatments for DED. The Symposium focused on the personal and collective burden of DED, as well as the developmental and regulatory challenges associated with generating new DED therapeutics. This article provides a synopsis of many of the presentations, discussions and recommendations of this Symposium.},
	keywords = {Dry Eye Syndromes, Global Health, Health Services Needs and Demand, Humans, Needs Assessment},
	issn = {1542-0124},
	doi = {10.1016/j.jtos.2012.02.001},
	author = {Sullivan, David A and Hammitt, Katherine M and Schaumberg, Debra A and Sullivan, Benjamin D and Begley, Carolyn G and Gjorstrup, Per and Garrigue, Jean-S{\'e}bastien and Nakamura, Masatsugu and Quentric, Yann and Barabino, Stefano and Dalton, Michelle and Novack, Gary D}
}
@article {341656,
	title = {Automated computation of arbor densities: a step toward identifying neuronal cell types},
	journal = {Front Neuroanat},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {139},
	abstract = {The shape and position of a neuron convey information regarding its molecular and functional identity. The identification of cell types from structure, a classic method, relies on the time-consuming step of arbor tracing. However, as genetic tools and imaging methods make data-driven approaches to neuronal circuit analysis feasible, the need for automated processing increases. Here, we first establish that mouse retinal ganglion cell types can be as precise about distributing their arbor volumes across the inner plexiform layer as they are about distributing the skeletons of the arbors. Then, we describe an automated approach to computing the spatial distribution of the dendritic arbors, or arbor density, with respect to a global depth coordinate based on this observation. Our method involves three-dimensional reconstruction of neuronal arbors by a supervised machine learning algorithm, post-processing of the enhanced stacks to remove somata and isolate the neuron of interest, and registration of neurons to each other using automatically detected arbors of the starburst amacrine interneurons as fiducial markers. In principle, this method could be generalizable to other structures of the CNS, provided that they allow sparse labeling of the cells and contain a reliable axis of spatial reference.},
	issn = {1662-5129},
	doi = {10.3389/fnana.2014.00139},
	author = {S{\"u}mb{\"u}l, Uygar and Zlateski, Aleksandar and Vishwanathan, Ashwin and Masland, Richard H and Seung, H Sebastian}
}
@article {1351199,
	title = {A genetic and computational approach to structurally classify neuronal types},
	journal = {Nat Commun},
	volume = {5},
	year = {2014},
	month = {2014 Mar 24},
	pages = {3512},
	abstract = {The importance of cell types in understanding brain function is widely appreciated but only a tiny fraction of neuronal diversity has been catalogued. Here we exploit recent progress in genetic definition of cell types in an objective structural approach to neuronal classification. The approach is based on highly accurate quantification of dendritic arbor position relative to neurites of other cells. We test the method on a population of 363 mouse retinal ganglion cells. For each cell, we determine the spatial distribution of the dendritic arbors, or arbor density, with reference to arbors of an abundant, well-defined interneuronal type. The arbor densities are sorted into a number of clusters that is set by comparison with several molecularly defined cell types. The algorithm reproduces the genetic classes that are pure types, and detects six newly clustered cell types that await genetic definition.},
	keywords = {Algorithms, Animals, Computational Biology, Dendrites, Image Processing, Computer-Assisted, Mice, Neurons, Retina},
	issn = {2041-1723},
	doi = {10.1038/ncomms4512},
	author = {S{\"u}mb{\"u}l, Uygar and Song, Sen and McCulloch, Kyle and Becker, Michael and Lin, Bin and Sanes, Joshua R and Masland, Richard H and Seung, H Sebastian}
}
@article {1623363,
	title = {Managing Center-Involved Diabetic Macular Edema With Good Visual Acuity},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {1},
	year = {2022},
	month = {2022 Jan 01},
	pages = {95-96},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.4664},
	author = {Sun, Jennifer K and Glassman, Adam R and Jampol, Lee M}
}
@article {1626107,
	title = {The Growing Need to Understand Diabetic Retinopathy Outcomes in Youth},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {1},
	year = {2022},
	month = {2022 Jan 01},
	pages = {57-58},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.5050},
	author = {Sun, Jennifer K}
}
@article {1059826,
	title = {Optic nerve astrocyte reactivity protects function in experimental glaucoma and other nerve injuries},
	journal = {J Exp Med},
	volume = {214},
	number = {5},
	year = {2017},
	month = {2017 May 01},
	pages = {1411-1430},
	abstract = {Reactive remodeling of optic nerve head astrocytes is consistently observed in glaucoma and other optic nerve injuries. However, it is unknown whether this reactivity is beneficial or harmful for visual function. In this study, we used the Cre recombinase (Cre)-loxP system under regulation of the mouse glial fibrillary acidic protein promoter to knock out the transcription factor signal transducer and activator of transcription 3 (STAT3) from astrocytes and test the effect this has on reactive remodeling, ganglion cell survival, and visual function after experimental glaucoma and nerve crush. After injury, STAT3 knockout mice displayed attenuated astrocyte hypertrophy and reactive remodeling; astrocytes largely maintained their honeycomb organization and glial tubes. These changes were associated with increased loss of ganglion cells and visual function over a 30-day period. Thus, reactive astrocytes play a protective role, preserving visual function. STAT3 signaling is an important mediator of various aspects of the reactive phenotype within optic nerve astrocytes.},
	issn = {1540-9538},
	doi = {10.1084/jem.20160412},
	author = {Sun, Daniel and Moore, Sara and Jakobs, Tatjana C}
}
@article {1295878,
	title = {Visualizing Astrocytes of the Optic Nerve},
	journal = {Methods Mol Biol},
	volume = {1695},
	year = {2018},
	month = {2018},
	pages = {269-286},
	abstract = {Astrocytes make up approximately 30\% of all the cells in the mammalian central nervous system. They are not passive, as once thought, but are integral to brain physiology and perform many functions that are important for normal neuronal development and metabolism, synapse formation, synaptic transmission, and in repair following injury/disease. Astrocytes also communicate with neurons, blood vessels, and other types of glial cells. Astrocytes within the optic nerve head region play a key role in glaucomatous axon degeneration. In this chapter, we describe ways in which astrocytes of the optic nerve head can be visualized, beginning with basic immunohistochemical staining methods, to single-cell dye injections and then to transgenic animals. We will also discuss the pros and cons of each method. Many of the methods were initially developed to visualize brain astrocytes; in some cases, the method has translated well to astrocytes of the optic nerve, and in others, it remains unclear.},
	issn = {1940-6029},
	doi = {10.1007/978-1-4939-7407-8_18},
	author = {Sun, Daniel}
}
@article {1806506,
	title = {Clinical Course and Visual Outcomes of Papilledema in Pediatric Cerebral Venous Sinus Thrombosis},
	journal = {Am J Ophthalmol},
	year = {2024},
	month = {2024 Feb 21},
	abstract = {PURPOSE: Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening event with significant neurologic and visual morbidity. In this study, we report on the natural history and visual outcomes of papilledema in children with CVST. DESIGN: Retrospective case series. METHODS: Patients with CVST evaluated by the Department of ophthalmology between 2000 and 2023 were included. Records were reviewed for presence and course of papilledema, treatment, and final visual outcomes following papilledema resolution. RESULTS: The study included 35 patients with a mean age of 9 {\textpm} 5 years and 40\% were female. The most common risk factors for CVST were infection (69\%), dehydration (26\%), and hypercoagulability (23\%). 31 patients (89\%) had papilledema. Of these patients, 9 (29\%) had progression of papilledema despite treatment, 17 patients (55\%) did not have progression, and 5 patients (16\%) lacked follow-up records. Initial Fris{\'e}n grade among all cases was 2 {\textpm} 1, and cases with progression reached a grade of 4 {\textpm} 1 between 10 and 32 days following initial identification. Most patients (97\%) were treated with anticoagulation and 100\% required acetazolamide and/or lumbar puncture. Among 26 patients with follow-up, papilledema resolved in 107 {\textpm} 128 days. 54\% of patients had permanent ophthalmic sequelae. An initial Fris{\'e}n grade >=3 (odds ratio [OR] 7.54, 95\% confidence interval [CI] 6.53-8.70, p \&lt;0.001) was significantly associated with eventual optic atrophy. CONCLUSIONS: Children with CVST are at high risk for ophthalmologic sequelae. Papilledema can progress despite appropriate therapy. Our results highlight the importance of ophthalmologic follow-up during treatment course to prevent irreversible vision loss.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2024.02.001},
	author = {Sun, Jessica A and Estrela, Tais and Gise, Ryan}
}
@article {1478341,
	title = {One-Time Intravitreal Injection of KVD001, a Plasma Kallikrein Inhibitor, in Patients with Central-Involved Diabetic Macular Edema and Reduced Vision: An Open-Label Phase 1B Study},
	journal = {Ophthalmol Retina},
	volume = {3},
	number = {12},
	year = {2019},
	month = {2019 Dec},
	pages = {1107-1109},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.07.006},
	author = {Sun, Jennifer K and Maturi, Raj K and Boyer, David S and Wells, John A and Gonzalez, Victor H and Tansley, Robert and Hernandez, Helen and Maetzel, Andreas and Feener, Edward P and Aiello, Lloyd Paul}
}
@article {1629448,
	title = {Investigation of changes in the activity and function of dry eye-associated brain regions using the amplitude of low-frequency fluctuations method},
	journal = {Biosci Rep},
	volume = {42},
	number = {1},
	year = {2022},
	month = {2022 01 28},
	abstract = {OBJECTIVE: The local characteristics of spontaneous brain activity in patients with dry eye (DE) and its relationship with clinical characteristics were evaluated using the amplitude of low-frequency fluctuations (ALFF) method. METHODS: A total of 27 patients with DE (10 males and 17 females) and 28 healthy controls (HCs) (10 males and 18 females) were recruited, matched according to sex, age, weight and height, classified into the DE and HC groups, and examined using functional magnetic resonance imaging (fMRI) scans. Spontaneous brain activity changes were recorded using ALFF technology. Data were recorded and plotted on the receiver operating characteristic (ROC) curve, reflecting changes in activity in different brain areas. Finally, Pearson correlation analysis was used to calculate the potential relationship between spontaneous brain activity abnormalities in multiple brain regions and clinical features in patients with DE. GraphPad Prism 8 (GraphPad Software, Inc.) was used to analyze the linear correlation between the Hospital Anxiety and Depression Scale and ALFF value. RESULTS: Compared with HCs, the ALFF values of patients with DE were decreased in the right middle frontal gyrus (MFG)/right inferior orbitofrontal cortex (OFC), left triangle inferior frontal gyrus, left MFG, and right superior frontal gyrus. In contrast, the ALFF value of patients with DE was increased in the left calcarine. CONCLUSION: There are significant fluctuations in the ALFF value of specific brain regions in patients with DE versus HCs. This corroborates previous evidence showing that the symptoms of ocular surface damage in patients with DE are related to dysfunction in specific brain areas.},
	keywords = {Aged, Brain, Brain Mapping, Brain Waves, Case-Control Studies, Dry Eye Syndromes, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Predictive Value of Tests, Reproducibility of Results},
	issn = {1573-4935},
	doi = {10.1042/BSR20210941},
	author = {Sun, Tie and Shu, Hui-Ye and Wu, Jie-Li and Su, Ting and Liu, Yu-Ji and Zhang, Li-Juan and Li, Qiu-Yu and Pan, Yi-Cong and Ge, Qian-Min and Shao, Yi}
}
@article {341771,
	title = {Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema.},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {11},
	year = {2014},
	month = {2014 Nov},
	pages = {1309-16},
	abstract = {IMPORTANCE: Biomarkers that predict future visual acuity (VA) in eyes with baseline diabetic macular edema (DME) would substantively improve risk assessment, management decisions, and selection of eyes for clinical studies targeting DME. OBJECTIVE: To determine whether baseline or early change in the novel spectral domain-optical coherence tomography (SD-OCT) parameter disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes with center-involved DME. DESIGN, SETTING, AND PARTICIPANTS: At a tertiary care referral center for diabetic eye disease, a retrospective, longitudinal cohort study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8-month visits in 96 participants (120 eyes) with diabetes mellitus and baseline center-involved DME (SD-OCT central subfield thickness, >= 320 {\textmu}m for men and >= 305 {\textmu}m for women). Exclusion criteria included substantial media opacity, cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA. On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone outer segment tip visibility, and external limiting membrane or photoreceptor disruption and reflectivity. MAIN OUTCOMES AND MEASURES: Visual acuity and SD-OCT-derived retinal morphology. RESULTS: Greater DRIL extent at baseline correlated with worse baseline VA (point estimate, 0.04; 95\% CI, 0.02-0.05 per 100 {\textmu}m; P \&lt; .001). An increase in DRIL during 4 months was associated with VA worsening at 8 months (point estimate, 0.03; 95\% CI, 0.02-0.05 per 100 {\textmu}m; P \&lt; .001). A multivariate model that included a 4-month change in VA, DRIL, and external limiting membrane disruption was predictive of an 8-month VA change (r = 0.80). Each approximately 300-{\textmu}m DRIL increase during 4 months predicted a 1-line, 8-month VA decline. When DRIL increased at least 250 {\textmu}m at 4 months, no eyes had VA improvement of at least 1 line at 8 months. When DRIL decreased at least 250 {\textmu}m at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7\% had VA improvement of at least 1 line. CONCLUSIONS AND RELEVANCE: Disorganization of the retinal inner layers in the 1-mm foveal area is associated with VA, and change in DRIL predicts future change in VA. Early change in DRIL prospectively identifies eyes with a high likelihood of subsequent VA improvement or decline. Therefore, DRIL warrants further study as a robust, readily obtained, and noninvasive biomarker of future VA response in eyes with DME.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.2350},
	author = {Sun, Jennifer K and Lin, Michael M and Lammer, Jan and Prager, Sonja and Sarangi, Rutuparna and Silva, Paolo S and Aiello, Lloyd Paul}
}
@article {509166,
	title = {Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {112},
	number = {33},
	year = {2015},
	month = {2015 Aug 18},
	pages = {10401-6},
	abstract = {Pathologic ocular angiogenesis is a leading cause of blindness, influenced by both dysregulated lipid metabolism and inflammation. Retinoic-acid-receptor-related orphan receptor alpha (RORα) is a lipid-sensing nuclear receptor with diverse biologic function including regulation of lipid metabolism and inflammation; however, its role in pathologic retinal angiogenesis remains poorly understood. Using a mouse model of oxygen-induced proliferative retinopathy, we showed that RORα expression was significantly increased and genetic deficiency of RORα substantially suppressed pathologic retinal neovascularization. Loss of RORα led to decreased levels of proinflammatory cytokines and increased levels of antiinflammatory cytokines in retinopathy. RORα directly suppressed the gene transcription of suppressors of cytokine signaling 3 (SOCS3), a critical negative regulator of inflammation. Inhibition of SOCS3 abolished the antiinflammatory and vasoprotective effects of RORα deficiency in vitro and in vivo. Moreover, treatment with a RORα inverse agonist SR1001 effectively protected against pathologic neovascularization in both oxygen-induced retinopathy and another angiogenic model of very-low-density lipoprotein receptor (Vldlr)-deficient (Vldlr (-/-) ) mice with spontaneous subretinal neovascularization, whereas a RORα agonist worsened oxygen-induced retinopathy. Our data demonstrate that RORα is a novel regulator of pathologic retinal neovascularization, and RORα inhibition may represent a new way to treat ocular neovascularization.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1504387112},
	author = {Sun, Ye and Liu, Chi-Hsiu and SanGiovanni, John Paul and Evans, Lucy P and Tian, Katherine T and Zhang, Bing and Stahl, Andreas and Pu, William T and Kamenecka, Theodore M and Solt, Laura A and Chen, Jing}
}
@article {560246,
	title = {SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth.},
	journal = {Sci Signal},
	volume = {8},
	number = {395},
	year = {2015},
	month = {2015},
	pages = {ra94},
	abstract = {Neurons and glial cells in the retina contribute to neovascularization, or the formation of abnormal new blood vessels, in proliferative retinopathy, a condition that can lead to vision loss or blindness. We identified a mechanism by which suppressor of cytokine signaling 3 (SOCS3) in neurons and glial cells prevents neovascularization. We found that Socs3 expression was increased in the retinal ganglion cell and inner nuclear layers after oxygen-induced retinopathy. Mice with Socs3 deficiency in neuronal and glial cells had substantially reduced vaso-obliterated retinal areas and increased pathological retinal neovascularization in response to oxygen-induced retinopathy, suggesting that loss of neuronal/glial SOCS3 increased both retinal vascular regrowth and pathological neovascularization. Furthermore, retinal expression of Vegfa (which encodes vascular endothelial growth factor A) was higher in these mice than in Socs3 flox/flox controls, indicating that neuronal and glial SOCS3 suppressed Vegfa expression during pathological conditions. Lack of neuronal and glial SOCS3 resulted in greater phosphorylation and activation of STAT3, which led to increased expression of its gene target Vegfa, and increased endothelial cell proliferation. In summary, SOCS3 in neurons and glial cells inhibited the STAT3-mediated secretion of VEGF from these cells, which suppresses endothelial cell activation, resulting in decreased endothelial cell proliferation and angiogenesis. These results suggest that neuronal and glial cell SOCS3 limits pathological retinal angiogenesis by suppressing VEGF signaling.},
	issn = {1937-9145},
	doi = {10.1126/scisignal.aaa8695},
	author = {Sun, Ye and Ju, Meihua and Lin, Zhiqiang and Fredrick, Thomas W and Evans, Lucy P and Tian, Katherine T and Saba, Nicholas J and Morss, Peyton C and Pu, William T and Chen, Jing and Stahl, Andreas and Joyal, Jean-S{\'e}bastien and Smith, Lois E H}
}
@article {1360122,
	title = {Durability of Diabetic Retinopathy Improvement with As-Needed Ranibizumab: Open-Label Extension of RIDE and RISE Studies},
	journal = {Ophthalmology},
	volume = {126},
	number = {5},
	year = {2019},
	month = {2019 May},
	pages = {712-720},
	abstract = {PURPOSE: To evaluate the durability of diabetic retinopathy (DR) improvements after a change in ranibizumab dosing from monthly to individualized pro re nata (PRN) therapy. DESIGN: Pooled analysis of the open-label extension (OLE) of RIDE and RISE (clinicaltrials.gov identifiers, NCT00473382 and NCT00473330) patients with DR and diabetic macular edema (DME). PARTICIPANTS: Patients who completed 36-month participation in RIDE and RISE and entered the OLE. METHODS: In RIDE and RISE, patients (n\&nbsp;= 759) were randomized 1:1:1 to ranibizumab 0.3 mg monthly, 0.5\&nbsp;mg monthly, or monthly sham injections with rescue macular laser available after 6 months, per protocol-specified criteria. After 24 months, sham patients crossed over to ranibizumab 0.5 mg monthly. After 36 months in the core studies, patients in the OLE (n\&nbsp;= 500) could receive ranibizumab 0.5 mg PRN based on predefined DME re-treatment criteria. Diabetic retinopathy severity was evaluated photographically using the Early Treatment Diabetic Retinopathy Study DR severity scale. MAIN OUTCOME MEASURES: Change in DR severity from months 36 to 48 by re-treatment status. RESULTS: Among patients who entered the OLE, 121 of 500 (24\%) did not require additional ranibizumab injections. Overall, 367 patients had evaluable DR at months 36 and 48. Among patients not requiring ranibizumab re-treatment from months 36 to 48 (88/367), 57\% to 78\%, 0\% to 7\%, and 22\% to 36\% experienced DR severity stability, 2-step or more improvement, and 2-step or more worsening, respectively. Among patients requiring ranibizumab re-treatment (279/367), 84\% to 94\%, 2\%, and 3\% to 14\% experienced DR severity stability, 2-step or more improvement, and 2-step or more worsening, respectively. On average, vision improvements were maintained during the OLE regardless of change in DR severity. CONCLUSIONS: Diabetic retinopathy severity improvements with ranibizumab were maintained in over 70\% of OLE patients after switching from ranibizumab monthly to an individualized ranibizumab 0.5 mg PRN dosing regimen. Because approximately one third of OLE patients experienced DR worsening, careful monitoring should be part of the long-term management of patients with DR.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.10.041},
	author = {Sun, Jennifer K and Wang, Pin-Wen and Taylor, Sarah and Haskova, Zdenka}
}
@article {1661808,
	title = {Challenges in the Clinical Management of Proliferative Diabetic Retinopathy: Treatment Choice and Follow-up},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {1},
	year = {2023},
	month = {2023 Jan 01},
	pages = {46-47},
	keywords = {Diabetes Mellitus, Type 1, Diabetic Retinopathy, Follow-Up Studies, Humans},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.5057},
	author = {Sun, Jennifer K and Liu, Danni}
}
@article {1782371,
	title = {Comparison of Structural and Functional Features in Primary Angle-Closure and Open-Angle Glaucomas},
	journal = {J Glaucoma},
	year = {2023},
	month = {2023 Nov 28},
	abstract = {PRECIS: Using a large dataset, we showed structural and functional differences between primary angle closure glaucoma and primary open angle glaucoma. Primary angle closure glaucoma has relative structural preservation and worse functional loss inferiorly. PURPOSE: To identify structural and functional differences in primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG). PATIENTS AND METHODS: In this large cross-sectional study, differences in structural and functional damage were assessed among POAG and PACG patients with optical coherence tomography and reliable visual field testing. RESULTS: 283 PACG and 4,110 POAG patients were included. Despite similar mean deviation on visual fields (mean [standard deviation] -7.73 [7.92] vs. -7.53 [6.90] dB, P=0.72), PACG patients had thicker global retinal nerve fiber layer (RNFL), smaller cup volume, smaller cup-to-disc ratio, and larger rim area than POAG (77 [20] vs. 71 [14] {\textmu}m, 0.32 [0.28] vs. 0.40 [0.29] mm3, 0.6 [0.2] vs. 0.7 [0.1], 1.07 [0.40] vs. 0.89 [0.30] mm2, P\&lt;0.001 for all), while POAG patients had more pronounced inferior RNFL thinning (82 [24] vs. 95 [35] {\textmu}m, P\&lt;0.001). In a multivariable analysis, hyperopia (odds ratio (OR): 1.24, confidence interval (CI): 1.13-1.37), smaller cup-to-disc ratio (OR: 0.69, CI: 0.61-0.78), thicker inferior RNFL (OR: 1.15, CI: 1.06-1.26) and worse mean deviation (OR: 0.95, CI: 0.92-0.98) were associated with PACG. Functionally, POAG was associated with superior paracentral loss and PACG with inferior field loss. After adjusting for average RNFL thickness, PACG was associated with more diffuse loss than POAG (TD differences 1.26-3.2 dB). CONCLUSIONS: PACG patients had less structural damage than POAG patients despite similar degrees of functional loss. Regional differences in patterns of functional and structural loss between POAG and PACG may improve disease monitoring for these glaucoma subtypes.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000002341},
	author = {Sun, Jessica A and Yuan, Melissa and Johnson, Grace E and Pasquale, Louis R and Boland, Michael V and Friedman, David S and Tobias Elze and Shen, Lucy Q and Wang, Mengyu}
}
@article {1688346,
	title = {DEFINING "STRONG" VERSUS "WEAK" RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR CENTER-INVOLVED DIABETIC MACULAR EDEMA},
	journal = {Retina},
	volume = {43},
	number = {4},
	year = {2023},
	month = {2023 Apr 01},
	pages = {616-623},
	abstract = {BACKGROUND/PURPOSE: To define "strong" versus "weak" antivascular endothelial growth factor (anti-VEGF) treatment response in eyes with center-involved diabetic macular edema (CI-DME). METHODS: Exploratory analyses of three DRCR Retina Network randomized trials of eyes with CI-DME treated with aflibercept, bevacizumab, or ranibizumab. Thresholds of 5-, 10-, and 15-letter gain defined strong visual acuity (VA) response when baseline VA was 20/25-20/32, 20/40-20/63, or 20/80-20/320, respectively. Thresholds of 50, 100, or 200- {\textmu} m reduction defined strong anatomical response when baseline central subfield thickness (CST) was \&lt;75, >=75 to \&lt;175, or >=175- {\textmu} m above standard thresholds. Additional thresholds from regression equations were calculated. RESULTS: At 24 weeks, outcomes for strong response were achieved by 476 of 958 eyes (50\%) for VA and 505 eyes (53\%) for CST. At 104 weeks among the 32\% of eyes with strong VA and CST response at 24 weeks, 195 of 281 (69\%) maintained strong VA and CST response, whereas 20 (7\%) had neither strong VA nor strong CST response. Outcomes rates were similar across protocols and when defined using regression equations. CONCLUSION: These phenotypes are suitable for efforts to identify predictive biomarkers for response to anti-VEGF therapy for DME and might facilitate comparison of treatment response among diverse cohorts with DME.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Diabetes Mellitus, Diabetic Retinopathy, Endothelial Growth Factors, Humans, Intravitreal Injections, Macular Edema, Ranibizumab, Receptors, Vascular Endothelial Growth Factor, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003730},
	author = {Sun, Jennifer K and Beaulieu, Wesley T and Melia, Michele and Ferris, Frederick L and Maturi, Raj K and Nielsen, Jared S and Solomon, Sharon D and Jampol, Lee M and DRCR Retina Network}
}
@article {1328906,
	title = {Rationale and Application of the Protocol S Anti-Vascular Endothelial Growth Factor Algorithm for Proliferative Diabetic Retinopathy},
	journal = {Ophthalmology},
	volume = {126},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {87-95},
	abstract = {PURPOSE: To present the rationale, guidelines, and results of ranibizumab treatment for proliferative diabetic retinopathy (PDR) in Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S. DESIGN: Post hoc analyses from a randomized clinical trial. PARTICIPANTS: Three hundred five participants (394 study eyes) having PDR without prior panretinal photocoagulation (PRP). METHODS: Intravitreous ranibizumab (0.5 mg) versus PRP for PDR. Ranbizumab-assigned eyes (n\&nbsp;= 191) received monthly injections for 6 months unless resolution was achieved after 4 injections. After 6 months, injections could be deferred if neovascularization was stable over 3 consecutive visits (sustained stability). If neovascularization worsened, monthly treatment resumed. Panretinal photocoagulation could be initiated for failure or futility criteria. MAIN OUTCOME MEASURES: Neovascularization status through 2 years. RESULTS: At 1 month, 19\% (35 of 188) of ranibizumab-assigned eyes showed complete neovascularization resolution and an additional 60\% (113) showed improvement. At 6 months, 52\% (80 of 153) showed neovascularization resolution, 3\% (4) were improved, 37\% (56) were stable, and 8\% (13) had worsened since the last visit. Among eyes with versus without resolved neovascularization at 6 months, the median (interquartile range) number of injections between 6 months and 2 years was 4 (1-7; n\&nbsp;= 73) versus 7 (4-11; n\&nbsp;= 67; P \&lt; 0.001). Injections were deferred in 68 of 73 eyes (93\%) meeting sustained stability at least once during the study; 62\% (42 of 68) resumed injections within 16 weeks after deferral. At 2 years, 43\% (66 of 154) showed neovascularization resolution, 5\% (7) showed improvement, 23\% (36) were stable, and 27\% (42) had worsened since the last visit. Only 3 eyes met criteria for failure or futility through 2 years. CONCLUSIONS: The DRCR.net treatment algorithm for PDR can provide excellent clinical outcomes through\&nbsp;2\&nbsp;years for patients initiating anti-vascular endothelial growth factor (VEGF) therapy for PDR. When choosing between anti-VEGF and PRP as first-line therapy for PDR, treatment decisions should be guided by\&nbsp;consideration of the relative advantages of each therapeutic method and anticipated patient compliance with follow-up and treatment recommendations.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.08.001},
	author = {Sun, Jennifer K and Glassman, Adam R and Beaulieu, Wesley T and Stockdale, Cynthia R and Bressler, Neil M and Flaxel, Christina and Gross, Jeffrey G and Shami, Michel and Jampol, Lee M and Diabetic Retinopathy Clinical Research Network}
}
@article {1626108,
	title = {Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {14},
	year = {2021},
	month = {2021 Dec 01},
	pages = {34},
	abstract = {Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70\% sample) and validate (30\% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95\% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 {\texttimes} Cirrus and Cirrus = 1.82 + 0.94 {\texttimes} Spectralis regardless of age, sex, or CST. Predicted values were within 10\% of observed values in 101 (90\%) of Spectralis and 99 (88\%) of Cirrus scans in the validation data; and in 136 (91\%) of the Spectralis and 148 (99\%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95\% of conversions are estimated to be within 17\% (95\% confidence interval, 14\%-21\%) of CST on Spectralis and within 22\% (95\% confidence interval, 18\%-28\%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.14.34},
	author = {Sun, Jennifer K and Josic, Kristin and Melia, Michele and Glassman, Adam R and Bailey, Clare and Chalam, Kakarla V and Chew, Emily Y and Cukras, Catherine and Grover, Sandeep and Jaffe, Glenn J and Lee, Richard and Nielsen, Jared S and Thompson, Darby J S and Wiley, Henry E and Ferris, Frederick L and DRCR Retina Network}
}
@article {1302168,
	title = {The SCORE2 Comparison of Treat-and-Extend vs Monthly Anti-Vascular Endothelial Growth Factor Dosing: Short-term Similarities and Longer-term Questions},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {4},
	year = {2018},
	month = {2018 Apr 01},
	pages = {346-347},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.6855},
	author = {Sun, Jennifer K}
}
@article {1658678,
	title = {A Step Forward in Understanding Treatment Approaches for Diabetic Macular Edema},
	journal = {JAMA Ophthalmol},
	year = {2022},
	month = {2022 Nov 10},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2022.4666},
	author = {Sun, Jennifer K and Baker, Carl W and Jampol, Lee M}
}
@article {1078816,
	title = {Comparing Anti-Vascular Endothelial Growth Factor Therapies for Central Retinal Vein Occlusion},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {6},
	year = {2017},
	month = {2017 Jun 01},
	pages = {649-650},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.1142},
	author = {Sun, Jennifer K}
}
@article {1333939,
	title = {Retinal Vasculature in Development and Diseases},
	journal = {Annu Rev Vis Sci},
	volume = {4},
	year = {2018},
	month = {2018 Sep 15},
	pages = {101-122},
	abstract = {The retina is one of the most metabolically active tissues in the body, consuming high levels of oxygen and nutrients. A well-organized ocular vascular system adapts to meet the metabolic requirements of the retina to ensure visual function. Pathological conditions affect growth of the blood vessels in the eye. Understanding the neuronal biological processes that govern retinal vascular development is of interest for translational researchers and clinicians to develop preventive and interventional therapeutics for vascular eye diseases that address early drivers of abnormal vascular growth. This review summarizes the current knowledge of the cellular and molecular processes governing both physiological and pathological retinal vascular development, which is dependent on the interaction among retinal cell populations, including neurons, glia, immune cells, and vascular endothelial cells. We also review animal models currently used for studying retinal vascular development.},
	issn = {2374-4650},
	doi = {10.1146/annurev-vision-091517-034018},
	author = {Sun, Ye and Smith, Lois E H}
}
@article {1307450,
	title = {SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS AND VISUAL OUTCOME AFTER TREATMENT FOR VITREOMACULAR TRACTION},
	journal = {Retina},
	volume = {39},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {1054-1060},
	abstract = {PURPOSE: To evaluate the capacity of spectral domain optical coherence tomography macular findings to predict best-corrected visual acuity (BCVA) outcomes after treatment for symptomatic vitreomacular traction. METHODS: This consecutive, retrospective study included 24 patients (29 eyes) who experienced vitreomacular traction release with pneumatic vitreolysis (n = 9), intravitreal ocriplasmin (n = 6), or pars plana vitrectomy (n = 14). Preoperative and postoperative spectral domain optical coherence tomography images were used to determine the cone outer segment tips (COST) line, inner segment/outer segment line, and other frequently used features. Correlations between optical coherence tomography findings and BCVA were determined using regression analyses. RESULTS: Postoperative BCVA was correlated with length of the COST line and inner segment/outer segment line defects at 1, 3, 6, and 12 months postoperatively (P \&lt; 0.05) by simple linear regression analysis. However, multivariable regression analysis showed that only length of the COST line defect was significantly correlated with BCVA preoperatively and postoperatively (P \&lt; 0.05). Postoperative BCVA improvement at 12 months was significantly correlated with preoperative length of the COST line defect (P \&lt; 0.01). CONCLUSION: Recovery of the COST line and inner segment/outer segment line defects as observed by spectral domain optical coherence tomography is positively correlated with visual acuity improvement after successful vitreomacular traction treatment. Best-corrected visual acuity improvement may be predicted using the length of the preoperative COST line defect.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000002116},
	author = {Sun, Peng and Tandias, Rachel M and Yu, Gina and Arroyo, Jorge G}
}
@article {369021,
	title = {Neural Retinal Disorganization as a Robust Marker of Visual Acuity in Current and Resolved Diabetic Macular Edema.},
	journal = {Diabetes},
	volume = {64},
	number = {7},
	year = {2015},
	month = {2015 Jul},
	pages = {2560-70},
	abstract = {Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting >=50\% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes.},
	issn = {1939-327X},
	doi = {10.2337/db14-0782},
	author = {Sun, Jennifer K and Radwan, Salma H and Soliman, Ahmed Z and Lammer, Jan and Lin, Michael M and Prager, Sonja G and Silva, Paolo S and Aiello, Lloyd Bryce and Aiello, Lloyd Paul}
}
@article {1538320,
	title = {Notice of Withdrawal: Retinal Vasculature in Development and Diseases},
	journal = {Annu Rev Vis Sci},
	year = {2020},
	month = {2020 10 15},
	abstract = {This article was withdrawn on October 15, 2020, at the request of the journal editors, with agreement from the authors, owing to a substantial amount of unattributed or improperly cited text overlap with other sources. In accordance with Annual Reviews{\textquoteright} commitment to transparency, the original PDF of the article remains available for download at .},
	issn = {2374-4650},
	doi = {10.1146/annurev-vs-04-091720-200001},
	author = {Sun, Ye and Smith, Lois E H}
}
@article {1466898,
	title = {The Diabetic Retinopathy Clinical Research Network (DRCR.net) and Its Contributions to the Treatment of Diabetic Retinopathy},
	journal = {Ophthalmic Res},
	year = {2019},
	month = {2019 Sep 25},
	pages = {1-6},
	abstract = {Over the past two decades, the Diabetic Retinopathy Clinical Research Network (now known as the DRCR Retina Network) has contributed to multiple and substantial advances in the clinical care of diabetic eye disease. Network studies helped establish anti-vascular endothelial growth factor (VEGF) agents as an effective alternative to panretinal photocoagulation for eyes with proliferative diabetic retinopathy (PDR) and as first-line therapy for eyes with visual impairment for diabetic macular edema (DME), defined treatment algorithms for the use of intravitreal medications in these conditions, and provided critical data to understand how to better evaluate the diabetic eye using optical coherence tomography and other imaging modalities. Ongoing DRCR.net studies will address whether anti-VEGF therapy is effective at preventing vision-threatening complications in eyes with severe non-proliferative diabetic retinopathy, if photobiomodulation has a beneficial effect in eyes with DME, and whether initiation of DME treatment with bevacizumab and rescue with aflibercept can provide visual outcomes as good as those achieved with aflibercept alone. Future plans for the Network also include the expansion into non-diabetic eye disease in areas such as age-related macular degeneration.},
	issn = {1423-0259},
	doi = {10.1159/000502779},
	author = {Sun, Jennifer K and Jampol, Lee M}
}
@article {1635646,
	title = {Spotlight on the DRCR Retina Network{\textquoteright}s Photobiomodulation for Diabetic Macular Edema Trial},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {4},
	year = {2022},
	month = {2022 Apr 01},
	pages = {304-306},
	keywords = {Clinical Trials as Topic, Diabetes Mellitus, Diabetic Retinopathy, Humans, Macular Edema, Ranibizumab, Retina, Tomography, Optical Coherence},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.6331},
	author = {Sun, Jennifer K and Glassman, Adam R and Jampol, Lee M}
}
@article {1351196,
	title = {Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis},
	journal = {FASEB J},
	volume = {28},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {3942-51},
	abstract = {Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94\% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P\&lt;0.01), compared to normal controls. More than 80\% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47\% in normal controls (P\&lt;0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26{\textpm}2 vs. 3{\textpm}1 μm/s, P\&lt;0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P\&lt;0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients.},
	keywords = {Aged, Animals, Apoptosis, Biomarkers, Blotting, Western, Capillaries, Case-Control Studies, Cell Proliferation, Cells, Cultured, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Early Diagnosis, Female, Humans, Immunoenzyme Techniques, Male, Molecular Imaging, Rabbits, Rats, Long-Evans, Real-Time Polymerase Chain Reaction, Retina, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Vascular Endothelial Growth Factor Receptor-2},
	issn = {1530-6860},
	doi = {10.1096/fj.14-251934},
	author = {Sun, Dawei and Nakao, Shintaro and Xie, Fang and Zandi, Souska and Bagheri, Abouzar and Kanavi, Mozhgan Rezaei and Samiei, Shahram and Soheili, Zahra-Soheila and Frimmel, Sonja and Zhang, Zhongyu and Ablonczy, Zsolt and Ahmadieh, Hamid and Hafezi-Moghadam, Ali}
}
@article {669296,
	title = {The Future of Ultrawide Field Imaging for Diabetic Retinopathy: Pondering the Retinal Periphery.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {3},
	year = {2016},
	month = {2016 Mar 1},
	pages = {247-8},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.5384},
	author = {Sun, Jennifer K and Aiello, Lloyd Paul}
}
@article {1078821,
	title = {Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos},
	journal = {J Exp Med},
	volume = {214},
	number = {6},
	year = {2017},
	month = {2017 Jun 05},
	pages = {1753-1767},
	abstract = {Pathological neovessels growing into the normally avascular photoreceptors cause vision loss in many eye diseases, such as age-related macular degeneration and macular telangiectasia. Ocular neovascularization is strongly associated with inflammation, but the source of inflammatory signals and the mechanisms by which these signals regulate the disruption of avascular privilege in photoreceptors are unknown. In this study, we found that c-Fos, a master inflammatory regulator, was increased in photoreceptors in a model of pathological blood vessels invading photoreceptors: the very low-density lipoprotein receptor-deficient (Vldlr(-/-) ) mouse. Increased c-Fos induced inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor (TNF), leading to activation of signal transducer and activator of transcription 3 (STAT3) and increased TNFα-induced protein 3 (TNFAIP3) in Vldlr(-/-) photoreceptors. IL-6 activated the STAT3/vascular endothelial growth factor A (VEGFA) pathway directly, and elevated TNFAIP3 suppressed SOCS3 (suppressor of cytokine signaling 3)-activated STAT3/VEGFA indirectly. Inhibition of c-Fos using photoreceptor-specific AAV (adeno-associated virus)-hRK (human rhodopsin kinase)-sh_c-fos or a chemical inhibitor substantially reduced the pathological neovascularization and rescued visual function in Vldlr(-/-) mice. These findings suggested that the photoreceptor c-Fos controls blood vessel growth into the normally avascular photoreceptor layer through the inflammatory signal-induced STAT3/VEGFA pathway.},
	issn = {1540-9538},
	doi = {10.1084/jem.20161645},
	author = {Sun, Ye and Lin, Zhiqiang and Liu, Chi-Hsiu and Gong, Yan and Liegl, Raffael and Fredrick, Thomas W and Meng, Steven S and Burnim, Samuel B and Wang, Zhongxiao and Akula, James D and Pu, William T and Chen, Jing and Smith, Lois E H}
}
@article {1698371,
	title = {Four-Year Visual Outcomes After Intravitreous Aflibercept for Vision-Threatening Complications of Diabetic Retinopathy-Reply},
	journal = {JAMA},
	volume = {329},
	number = {20},
	year = {2023},
	month = {2023 May 23},
	pages = {1796},
	keywords = {Angiogenesis Inhibitors, Blindness, Diabetes Mellitus, Diabetic Retinopathy, Humans},
	issn = {1538-3598},
	doi = {10.1001/jama.2023.6715},
	author = {Sun, Jennifer K and Glassman, Adam R and Maturi, Raj K and DRCR Retina Network}
}
@article {1435416,
	title = {Clinical Applicability of Assessing Peripheral Nonperfusion on Ultra-Widefield Angiography: Predicting Proliferative Diabetic Retinopathy},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Apr 11},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.0411},
	author = {Sun, Jennifer K}
}
@article {1109876,
	title = {RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis},
	journal = {FASEB J},
	volume = {31},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {4492-4502},
	abstract = {Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood. Here we showed that retinoic acid receptor-related orphan receptor α (RORα), a nuclear receptor and transcription factor, is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in a mouse model of oxygen-induced proliferative retinopathy. We found that genetic deficiency of RORα substantially induced Sema3e expression in retinopathy. Both RORα and SEMA3E were expressed in retinal ganglion cells. RORα directly bound to a specific ROR response element on the promoter of Sema3e and negatively regulated Sema3e promoter-driven luciferase expression. Suppression of Sema3e using adeno-associated virus 2 carrying short hairpin RNA targeting Sema3e promoted disoriented pathological neovascularization and partially abolished the inhibitory vascular effects of RORα deficiency in retinopathy. Our findings suggest that RORα is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in pathological retinal angiogenesis.-Sun, Y., Liu, C.-H., Wang, Z., Meng, S. S., Burnim, S. B., SanGiovanni, J. P., Kamenecka, T. M., Solt, L. A., Chen, J. RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis.},
	issn = {1530-6860},
	doi = {10.1096/fj.201700172R},
	author = {Sun, Ye and Liu, Chi-Hsiu and Wang, Zhongxiao and Meng, Steven S and Burnim, Samuel B and SanGiovanni, John Paul and Kamenecka, Theodore M and Solt, Laura A and Chen, Jing}
}
@article {1677666,
	title = {Glaucoma management in patients with penetrating keratoplasty or keratoprosthesis},
	journal = {Curr Opin Ophthalmol},
	volume = {34},
	number = {2},
	year = {2023},
	month = {2023 Mar 01},
	pages = {95-102},
	abstract = {PURPOSE OF REVIEW: Advances in surgical techniques and postoperative care have significantly improved rates of short-term complications following keratoplasty; however, glaucoma remains a highly prevalent long-term and potentially devastating complication for postkeratoplasty patients. In this review, we provide an overview of recent literature on glaucoma management in patients who have undergone penetrating keratoplasty or the Boston keratoprosthesis type I (KPro) implantation. RECENT FINDINGS: New research suggests an inflammatory cause underlying glaucoma following KPro. Accurate IOP measurement is difficult in patients postkeratoplasty; study of objective techniques such as PDCT or Tono-Pen in penetrating keratoplasty eyes and trans-palpebral Diaton tonometry in KPro eyes have shown promising results. Early glaucoma surgical intervention should be considered for patients undergoing penetrating keratoplasty and KPro. SUMMARY: Patients who have undergone penetrating keratoplasty or implantation of the Boston keratoprosthesis type I should be monitored frequently for elevated intraocular pressure and for other signs of glaucomatous optic nerve damage. Intraocular pressure elevation should be treated promptly either medically or surgically while minimizing risk to the corneal graft. Further research into inflammatory causes and other treatment modalities is promising for the long-term visual success in these patients.},
	keywords = {Cornea, Corneal Diseases, Glaucoma, Humans, Intraocular Pressure, Keratoplasty, Penetrating, Prostheses and Implants, Retrospective Studies},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000924},
	author = {Sun, Jessica A and Manz, Sarah N and Shen, Lucy Q}
}
@article {1307460,
	title = {A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure},
	journal = {Am J Hum Genet},
	volume = {102},
	number = {3},
	year = {2018},
	month = {2018 Mar 01},
	pages = {375-400},
	abstract = {Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined \~{}18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p \&lt; 5\&nbsp;{\texttimes} 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p \&lt; 5\&nbsp;{\texttimes} 10). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2018.01.015},
	author = {Sung, Yun J and Winkler, Thomas W and de Las Fuentes, Lisa and Bentley, Amy R and Brown, Michael R and Kraja, Aldi T and Schwander, Karen and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Lu, Yingchang and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K and Li, Changwei and Feitosa, Mary F and Kilpel{\"a}inen, Tuomas O and Richard, Melissa A and Noordam, Raymond and Aslibekyan, Stella and Aschard, Hugues and Bartz, Traci M and Dorajoo, Rajkumar and Liu, Yongmei and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert Vernon and Tajuddin, Salman M and Tayo, Bamidele O and Warren, Helen R and Zhao, Wei and Zhou, Yanhua and Matoba, Nana and Sofer, Tamar and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gandin, Ilaria and Gao, Chuan and Giulianini, Franco and Goel, Anuj and Harris, Sarah E and Hartwig, Fernando Pires and Horimoto, Andrea R V R and Hsu, Fang-Chi and Jackson, Anne U and K{\"a}h{\"o}nen, Mika and Kasturiratne, Anuradhani and K{\"u}hnel, Brigitte and Leander, Karin and Lee, Wen-Jane and Lin, Keng-Hung and Luan, Jian{\textquoteright}an and McKenzie, Colin A and Meian, He and Nelson, Christopher P and Rauramaa, Rainer and Schupf, Nicole and Scott, Robert A and Sheu, Wayne H H and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Wang, Heming and Wang, Yajuan and Ware, Erin B and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Alfred, Tamuno and Amin, Najaf and Arking, Dan and Aung, Tin and Barr, R Graham and Bielak, Lawrence F and Boerwinkle, Eric and Bottinger, Erwin P and Braund, Peter S and Brody, Jennifer A and Broeckel, Ulrich and Cabrera, Claudia P and Cade, Brian and Caizheng, Yu and Campbell, Archie and Canouil, Micka{\"e}l and Chakravarti, Aravinda and CHARGE Neurology Working Group and Chauhan, Ganesh and Christensen, Kaare and Cocca, Massimiliano and COGENT-Kidney Consortium and Collins, Francis S and Connell, John M and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Debette, Stephanie and D{\"o}rr, Marcus and Duan, Qing and Eaton, Charles B and Ehret, Georg and Evangelou, Evangelos and Faul, Jessica D and Fisher, Virginia A and Forouhi, Nita G and Franco, Oscar H and Friedlander, Yechiel and Gao, He and GIANT Consortium and Gigante, Bruna and Graff, Misa and Gu, C Charles and Gu, Dongfeng and Gupta, Preeti and Hagenaars, Saskia P and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Hofman, Albert and Howard, Barbara V and Hunt, Steven and Irvin, Marguerite R and Jia, Yucheng and Joehanes, Roby and Justice, Anne E and Katsuya, Tomohiro and Kaufman, Joel and Kerrison, Nicola D and Khor, Chiea Chuen and Koh, Woon-Puay and Koistinen, Heikki A and Komulainen, Pirjo and Kooperberg, Charles and Krieger, Jose E and Kubo, Michiaki and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and LifeLines Cohort Study and Lim, Sing Hui and Lin, Shiow and Liu, Ching-Ti and Liu, Jianjun and Liu, Jingmin and Liu, Kiang and Liu, Yeheng and Loh, Marie and Lohman, Kurt K and Long, Jirong and Louie, Tin and M{\"a}gi, Reedik and Mahajan, Anubha and Meitinger, Thomas and Metspalu, Andres and Milani, Lili and Momozawa, Yukihide and Morris, Andrew P and Mosley, Thomas H and Munson, Peter and Murray, Alison D and Nalls, Mike A and Nasri, Ubaydah and Norris, Jill M and North, Kari and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmas, Walter R and Palmer, Nicholette D and Pankow, James S and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and Raitakari, Olli T and Renstr{\"o}m, Frida and Rice, Treva K and Ridker, Paul M and Robino, Antonietta and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Sabanayagam, Charumathi and Salako, Babatunde L and Sandow, Kevin and Schmidt, Carsten O and Schreiner, Pamela J and Scott, William R and Seshadri, Sudha and Sever, Peter and Sitlani, Colleen M and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Uitterlinden, Andr{\'e} G and Waldenberger, Melanie and Wang, Lihua and Wang, Ya X and Wei, Wen Bin and Williams, Christine and Wilson, Gregory and Wojczynski, Mary K and Yao, Jie and Yuan, Jian-Min and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and Chambers, John C and Chen, Yii-Der Ida and de Faire, Ulf and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Forrester, Terrence and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Horta, Bernardo Lessa and Hung, Yi-Jen and Jonas, Jost B and Kato, Norihiro and Kooner, Jaspal S and Laakso, Markku and Lehtim{\"a}ki, Terho and Liang, Kae-Woei and Magnusson, Patrik K E and Newman, Anne B and Oldehinkel, Albertine J and Pereira, Alexandre C and Redline, Susan and Rettig, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zheng, Wei and Kamatani, Yoichiro and Laurie, Cathy C and Bouchard, Claude and Cooper, Richard S and Evans, Michele K and Gudnason, Vilmundur and Kardia, Sharon L R and Kritchevsky, Stephen B and Levy, Daniel and O{\textquoteright}Connell, Jeff R and Psaty, Bruce M and van Dam, Rob M and Sims, Mario and Arnett, Donna K and Mook-Kanamori, Dennis O and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and Fornage, Myriam and Rotimi, Charles N and Province, Michael A and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Loos, Ruth J F and Reiner, Alex P and Rotter, Jerome I and Zhu, Xiaofeng and Bierut, Laura J and Gauderman, W James and Caulfield, Mark J and Elliott, Paul and Rice, Kenneth and Munroe, Patricia B and Morrison, Alanna C and Cupples, L Adrienne and Rao, Dabeeru C and Chasman, Daniel I}
}
@article {1782436,
	title = {Corneal Superficial Plaque Formation After Recombinant Human Nerve Growth Factor Use in a Patient With Neurotrophic Keratopathy and Limbal Stem Cell Deficiency From Mucous Membrane Pemphigoid},
	journal = {Cornea},
	year = {2023},
	month = {2023 Nov 27},
	abstract = {PURPOSE: The aim of this study was to report a rare observation of corneal superficial plaque formation after topical recombinant human nerve growth factor (rhNGF) treatment for a nonhealing epithelial defect in a patient with advanced mucous membrane pemphigoid, limbal stem cell deficiency, and neurotrophic keratopathy. METHODS: This study was a case report. RESULTS: A 72-year-old man with a complex course of mucous membrane pemphigoid, leading to cicatrizing keratoconjunctivits, limbal stem cell deficiency, and neurotrophic keratopathy presented with a recurrent persistent epithelial defect in the right eye. After a long course of unsuccessful epithelial healing, despite various treatment modalities, he was administered topical rhNGF (cenegermin 0.002\%; Oxervate, Domp{\'e} US Inc., Boston, MA) which successfully resolved the epithelial defect. However, on day 22 posttreatment, an unusual white, thick, adherent corneal superficial plaque formed. rhNGF was stopped and the plaque was carefully removed. Subsequently, there was no recurrence, and the patient{\textquoteright}s epithelial healing remained stable. CONCLUSIONS: Although the successful resolution of the persistent epithelial defect with rhNGF administration was notable, the development of the unusual epithelial overgrowth emphasizes the importance of vigilant monitoring and evaluation when using rhNGF in complex ocular conditions. Making informed decisions on the timing of discontinuing rhNGF can lead to desirable effects of the drug while mitigating additional side effects when managing such challenging cases.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003442},
	author = {Surico, Pier Luigi and Kaufman, Aaron R and Lin, Julie and Dehghani, Shima and Dana, Reza}
}
@article {1589750,
	title = {Variability and Power to Detect Progression of Different Visual Field Patterns},
	journal = {Ophthalmol Glaucoma},
	volume = {4},
	number = {6},
	year = {2021},
	month = {2021 Nov-Dec},
	pages = {617-623},
	abstract = {PURPOSE: To compare the variability and ability to detect visual field (VF) progression of 24-2, central 12 locations of the 24-2 and 10-2 VF tests in eyes with abnormal VFs. DESIGN: Retrospective, multisite cohort. PARTICIPANTS: A total of 52 806 24-2 and 11 966 10-2 VF tests from 7307 eyes from the Glaucoma Research Network database were analyzed. Only eyes with >= 5 visits and >= 2 years of follow-up were included. METHODS: Linear regression models were used to calculate the rates of mean deviation (MD) change (slopes), whereas their residuals were used to assess variability across the entire MD range. Computer simulations (n\&nbsp;= 10 000) based on real MD residuals of our sample were performed to estimate power to detect significant progression (P \&lt; 5\%) at various rates of MD change. MAIN OUTCOME MEASURES: Time required to detect progression. RESULTS: For all 3 patterns, the MD variability was highest within the\&nbsp;-5 to\&nbsp;-20 decibel (dB) range and consistently lower with the 10-2 compared with 24-2 or central 24-2. Overall, time to detect confirmed significant progression at 80\% power was the lowest with 10-2 VF, with a decrease of 14.6\% to 18.5\% when compared with 24-2 and a decrease of 22.9\% to 26.5\% when compared with central 24-2. CONCLUSIONS: Time to detect central VF progression was reduced with 10-2 MD compared with 24-2 and C24-2 MD in glaucoma eyes in this large dataset, in part because 10-2 tests had lower variability. These findings contribute to current evidence of the potential value of 10-2 testing in the clinical management of patients with glaucoma and in clinical trial design.},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.04.004},
	author = {Susanna, Fernanda N and Melchior, Bruna and Paula, Jayter S and Boland, Michael V and Myers, Jonathan S and Wellik, Sarah R and Tobias Elze and Pasquale, Louis R and Shen, Lucy Q and Ritch, Robert and Susanna, Remo and Hood, Donald C and Liebmann, Jeffrey M and De Moraes, Carlos Gustavo}
}
@article {1647890,
	title = {Younger Age and Albuminuria are Associated with Proliferative Diabetic Retinopathy and Diabetic Macular Edema in the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study},
	journal = {Curr Eye Res},
	volume = {47},
	number = {10},
	year = {2022},
	month = {2022 10},
	pages = {1389-1396},
	abstract = {Purpose: The purpose of the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study is to identify non-genetic and genetic risk factors associated with diabetic retinopathy (DR). This report examines the non-genetic risk factors for DR in South Indian patients.Methods: Participants with South Indian ancestry and type 2 diabetes (T2D) were included from two sources: the Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study (SN-DREAMS) and prospective recruitment at Sankara Nethralaya affiliates. Fundus photography and optical coherence tomography (OCT) were obtained on participants. Fundus images were graded for DR severity and OCTs were graded for center-involved diabetic macular edema (ciDME). Multivariate analyses were performed using stepwise logistic regression to assess effects of the demographic and clinical factors on proliferative DR (PDR) and DME.Results: Among the 2941 participants with DR grading, participants with PDR were more likely to be younger [odds ratio (OR)=0.95], men (OR = 1.83), have a longer duration of diabetes (OR = 1.10), have a higher hemoglobin A1c (OR = 1.12), have albuminuria (OR = 5.83), have hypertension (OR = 1.69), have a higher HDL (OR = 1.02) and a lower total cholesterol (OR = 0.99) (all p \&lt; 0.05). Among the 483 participants with gradable OCT scans, participants who had ciDME were more likely to be younger (OR = 0.97), men (OR = 2.80), have a longer duration of diabetes (OR = 1.06), have lower triglycerides (OR = 0.99), and have albuminuria (OR = 3.12) (all p \&lt; 0.05).Conclusions: Younger age, male sex, longer duration of diabetes, higher HbA1c, and presence of albuminuria were identified as risk factors for PDR and DME in a South Indian population with T2D.},
	keywords = {Albuminuria, Cholesterol, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Glycated Hemoglobin A, Humans, Macular Edema, Male, Prospective Studies, Risk Factors, Triglycerides},
	issn = {1460-2202},
	doi = {10.1080/02713683.2022.2091148},
	author = {Susarla, Gayatri and Rizza, A N and Li, Ashley and Han, Samuel and Khan, Rehana and Chan, Weilin and Lains, Ines and Apivatthakakul, Atitaya and Brustoski, Kim and Khetan, Vikas and Raman, Rajiv and Igo, Robert P and Iyengar, Sudha K and Mathavan, Sinnakaruppan and Sobrin, Lucia}
}
@article {1661809,
	title = {Mendelian Randomization Shows a Causal Effect of Low Vitamin D on Non-infectious Uveitis and Scleritis Risk},
	journal = {Am J Ophthalmol},
	volume = {244},
	year = {2022},
	month = {2022 Dec},
	pages = {11-18},
	abstract = {PURPOSE: To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. DESIGN: Two-sample Mendelian randomization case-control study. METHODS: The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated. RESULTS: We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR]\&nbsp;=\&nbsp;2.16, 95\% CI\&nbsp;=\&nbsp;1.01-4.64, P\&nbsp;=\&nbsp;.049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR\&nbsp;=\&nbsp;2.38, 95\% CI =1.06-5.36, P\&nbsp;=\&nbsp;0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR\&nbsp;=\&nbsp;6.42, 95\% CI\&nbsp;=\&nbsp;3.19-12.89, P\&nbsp;=\&nbsp;1.7\&nbsp;{\texttimes}\&nbsp;10-7, per SD of log25OHD). CONCLUSIONS: Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.},
	keywords = {Case-Control Studies, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Scleritis, Uveitis, Vitamin D, Vitamins},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.08.001},
	author = {Susarla, Gayatri and Chan, Weilin and Li, Ashley and Davoudi, Samaneh and Ahmadi, Tina and Sathe, Shaleen and Tom, Lisa and Papaliodis, George N and Mercader, Josep M and Leong, Aaron and Sobrin, Lucia}
}
@article {1364555,
	title = {Wall teichoic acid protects Staphylococcus aureus from inhibition by Congo red and other dyes},
	journal = {J Antimicrob Chemother},
	volume = {67},
	number = {9},
	year = {2012},
	month = {2012 Sep},
	pages = {2143-51},
	abstract = {OBJECTIVES: Polyanionic polymers, including lipoteichoic acid and wall teichoic acid, are important determinants of the charged character of the staphylococcal cell wall. This study was designed to investigate the extent to which teichoic acid contributes to protection from anionic azo dyes and to identify barriers to drug penetration for development of new antibiotics for multidrug-resistant Staphylococcus aureus infection. METHODS: We studied antimicrobial activity of azo dyes against S. aureus strains with or without inhibition of teichoic acid in vitro and in vivo. RESULTS: We observed that inhibition of wall teichoic acid expression resulted in an \~{}1000-fold increase in susceptibility to azo dyes such as Congo red, reducing its MIC from \&gt;1024 to \&lt;4 mg/L. Sensitization occurred when the first step in the wall teichoic acid pathway, catalysed by TarO, was inhibited either by mutation or by chemical inhibition. In contrast, genetic blockade of lipoteichoic acid biosynthesis did not confer Congo red susceptibility. Based on this finding, combination therapy was tested using the highly synergistic combination of Congo red plus tunicamycin at sub-MIC concentrations (to inhibit wall teichoic acid biosynthesis). The combination rescued Caenorhabditis elegans from a lethal challenge of S. aureus. CONCLUSIONS: Our studies show that wall teichoic acid confers protection to S. aureus from anionic azo dyes and related compounds, and its inhibition raises the prospect of development of new combination therapies based on this inhibition.},
	keywords = {Anti-Bacterial Agents, Azo Compounds, Cell Wall, Congo Red, Humans, Microbial Sensitivity Tests, Staphylococcus aureus, Teichoic Acids},
	issn = {1460-2091},
	doi = {10.1093/jac/dks184},
	author = {Suzuki, Takashi and Campbell, Jennifer and Kim, Younghoon and Swoboda, Jonathan G and Mylonakis, Eleftherios and Walker, Suzanne and Gilmore, Michael S}
}
@article {1059831,
	title = {Cochlear gene therapy with ancestral AAV in adult mice: complete transduction of inner hair cells without cochlear dysfunction},
	journal = {Sci Rep},
	volume = {7},
	year = {2017},
	month = {2017 Apr 03},
	pages = {45524},
	abstract = {The use of viral vectors for inner ear gene therapy is receiving increased attention for treatment of genetic hearing disorders. Most animal studies to date have injected viral suspensions into neonatal ears, via the round window membrane. Achieving transduction of hair cells, or sensory neurons, throughout the cochlea has proven difficult, and no studies have been able to efficiently transduce sensory cells in adult ears while maintaining normal cochlear function. Here, we show, for the first time, successful transduction of all inner hair cells and the majority of outer hair cells in an adult cochlea via virus injection into the posterior semicircular canal. We used a "designer" AAV, AAV2/Anc80L65, in which the main capsid proteins approximate the ancestral sequence state of AAV1, 2, 8, and 9. Our injections also transduced ~10\% of spiral ganglion cells and a much larger fraction of their satellite cells. In the vestibular sensory epithelia, the virus transduced large numbers of hair cells and virtually all the supporting cells, along with close to half of the vestibular ganglion cells. We conclude that this viral vector and this delivery route hold great promise for gene therapy applications in both cochlear and vestibular sense organs.},
	issn = {2045-2322},
	doi = {10.1038/srep45524},
	author = {Suzuki, Jun and Hashimoto, Ken and Xiao, Ru and Vandenberghe, Luk H and Liberman, M Charles}
}
@article {1364554,
	title = {Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {7},
	year = {2012},
	month = {2012 Jun 28},
	pages = {4158-69},
	abstract = {PURPOSE: To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU). METHODS: C57BL/6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-γ, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-Ab) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured. RESULTS: AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression. CONCLUSIONS: AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR.},
	keywords = {Aminoimidazole Carboxamide, Animals, Autoimmune Diseases, Blotting, Western, Cell Proliferation, Cytokines, Disease Models, Animal, Female, Flow Cytometry, Hypoglycemic Agents, Immunity, Cellular, Injections, Intraperitoneal, Mice, Mice, Inbred C57BL, Ribonucleotides, T-Lymphocytes, Treatment Outcome, Uvea, Uveitis},
	issn = {1552-5783},
	doi = {10.1167/iovs.11-9323},
	author = {Suzuki, Jun and Yoshimura, Takeru and Simeonova, Marina and Takeuchi, Kimio and Murakami, Yusuke and Morizane, Yuki and Miller, Joan W and Sobrin, Lucia and Vavvas, Demetrios G}
}
@article {1309960,
	title = {Relation of Retinopathy of Prematurity to Brain Volumes at Term Equivalent Age and Developmental Outcome at 2 Years of Corrected Age in Very Preterm Infants},
	journal = {Neonatology},
	volume = {114},
	number = {1},
	year = {2018},
	month = {2018 Apr 12},
	pages = {46-52},
	abstract = {BACKGROUND: Retinopathy of prematurity (ROP) is a major complication of preterm birth and has been associated with later visual and nonvisual impairments. OBJECTIVES: To evaluate relationships between any stage of ROP, brain volumes, and developmental outcomes. METHODS: This study included 52 very preterm infants (gestational age [mean {\textpm} SD]: 26.4 {\textpm} 1.9 weeks). Total brain, gray matter, unmyelinated white matter (UWMV), and cerebellar volumes were estimated in 51 out of 52 infants by magnetic resonance imaging at term-equivalent age. Bayley Scales of Infant Development were used to assess developmental outcomes in 49 out of 52 infants at a mean corrected age of 24.6 months. RESULTS: Nineteen out of 52 infants developed any stage of ROP. Infants with ROP had a lower median (IQR) UWMV (173 [156-181] vs. 204 [186-216] mL, p \&lt; 0.001) and cerebellar volume (18.3 [16.5-20] vs. 22.3 [20.3-24.7] mL, p \&lt; 0.001) than infants without ROP. They also had a lower median (IQR) mental developmental index (72 [56-83] vs. 100 [88-104], p \&lt; 0.001) and a lower psychomotor developmental index (80 [60-85] vs. 92 [81-103], p = 0.002). Brain volumes and developmental outcomes did not differ among infants with different stages of ROP. CONCLUSION: Any stage of ROP in preterm infants was associated with a reduced brain volume and an impaired developmental outcome. These results suggest that common pathways may lead to impaired neural and neurovascular development in the brain and retina and that all stages of ROP may be considered in future studies on ROP and development.},
	issn = {1661-7819},
	doi = {10.1159/000487847},
	author = {Sveinsd{\'o}ttir, Kristbj{\"o}rg and Ley, David and H{\"o}vel, Holger and Fellman, Vineta and H{\"u}ppi, Petra S and Smith, Lois E H and Hellstr{\"o}m, Ann and Hansen Pupp, Ingrid}
}
@article {1351197,
	title = {TGF-β2-mediated ocular hypertension is attenuated in SPARC-null mice},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {7},
	year = {2014},
	month = {2014 Jun 06},
	pages = {4084-97},
	abstract = {PURPOSE: Transforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of primary open-angle glaucoma through extracellular matrix (ECM) alteration among various mechanisms. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates ECM within the trabecular meshwork (TM), and is highly upregulated by TGF-β2. We hypothesized that, in vivo, SPARC is a critical regulatory node in TGF-β2-mediated ocular hypertension. METHODS: Empty (Ad.empty) or TGF-β2-containing adenovirus (Ad.TGF-β2) was injected intravitreally into C57BL6-SV129 WT and SPARC-null mice. An initial study was performed to identify a stable period for IOP measurement under isoflurane. The IOP was measured before injection and every other day for two weeks using rebound tonometry. Additional mice were euthanized at peak IOP for immunohistochemistry. RESULTS: The IOP was stable under isoflurane during minutes 5 to 8. The IOP was significantly elevated in Ad.TGF-β2-injected (n = 8) versus Ad.empty-injected WT (n = 8) mice and contralateral uninjected eyes during days 4 to 11 (P \&lt; 0.03). The IOPs were not significantly elevated in Ad.TGF-β2-injected versus Ad.empty-injected SPARC-null mice. However, on day 8, the IOP of Ad.TGF-β2-injected SPARC-null eyes was elevated compared to that of contralateral uninjected eyes (P = 0.0385). Immunohistochemistry demonstrated that TGF-β2 stimulated increases in collagen IV, fibronectin, plasminogen activator inhibitor-1 (PAI-1), connective tissue growth factor (CTGF), and SPARC in WT mice, but only PAI-1 and CTGF in SPARC-null mice (P \&lt; 0.05). CONCLUSIONS: SPARC is essential to the regulation of TGF-β2-mediated ocular hypertension. Deletion of SPARC significantly attenuates the effects of TGF-β2 by restricting collagen IV and fibronectin expression. These data provide further evidence that SPARC may have an important role in IOP regulation and possibly glaucoma pathogenesis.},
	keywords = {Animals, Anterior Eye Segment, Disease Models, Animal, Immunoblotting, Immunohistochemistry, Intraocular Pressure, Intravitreal Injections, Mice, Mice, Inbred C57BL, Ocular Hypertension, Osteonectin, Transforming Growth Factor beta2},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12463},
	author = {Swaminathan, Swarup S and Oh, Dong-Jin and Kang, Min Hyung and Shepard, Allan R and Pang, Iok-Hou and Rhee, Douglas J}
}
@article {314206,
	title = {Aqueous outflow: segmental and distal flow},
	journal = {J Cataract Refract Surg},
	volume = {40},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {1263-72},
	abstract = {UNLABELLED: The elevated intraocular pressure (IOP) of primary open-angle glaucoma is caused by impaired outflow of aqueous humor through the trabecular meshwork. Within the juxtacanalicular region, alterations of both extracellular matrix homeostasis and the cellular tone of trabecular meshwork endothelial and the inner wall of Schlemm canal cells affect outflow. Newer pharmacologic agents that target trabecular meshwork and Schlemm canal cell cytoskeleton lower IOP. Aqueous drainage occurs nonhomogenously with greater flow going through certain portions of the TM and less going through other portions-a concept known as segmental flow, which is theoretically the result of outflow being dependent on the presence of discrete pores within Schlemm canal. The limited long-term success of trabecular meshwork bypass surgeries implicates the potential impact of resistance in Schlemm canal itself and collector channels. Additionally, others have observed that outflow occurs preferentially near collector channels. These distal structures may be more important to aqueous outflow than previously believed. FINANCIAL DISCLOSURE: Dr. Rhee is a consultant to Aerie Pharmaceuticals, Alcon Laboratories, Inc., Allegan, Inc., Aquesys, Inc., Glaukos Corp., Ivantis, Inc., Johnson \&amp; Johnson, Merck Sharp \&amp; Dohme Corp. and Santen, Inc., and has received research funding from Alcon Laboratories, Inc., Merck Sharp \&amp; Dohme Corp., and Ivantis, Inc. No other author has a financial or proprietary interest in any material or method mentioned.},
	keywords = {Antihypertensive Agents, Aqueous Humor, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Trabecular Meshwork},
	issn = {1873-4502},
	doi = {10.1016/j.jcrs.2014.06.020},
	author = {Swaminathan, Swarup S and Oh, Dong-Jin and Kang, Min Hyung and Rhee, Douglas J}
}
@article {1363210,
	title = {Secreted protein acidic and rich in cysteine (SPARC)-null mice exhibit more uniform outflow},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {3},
	year = {2013},
	month = {2013 Mar 21},
	pages = {2035-47},
	abstract = {PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) in many tissues and is highly expressed in trabecular meshwork (TM). SPARC-null mice have a 15\% to 20\% decrease in intraocular pressure (IOP) compared to wild-type (WT) mice. We hypothesized that mouse aqueous outflow is segmental, and that transgenic deletion of SPARC causes a more uniform pattern that correlates with IOP and TM morphology. METHODS: Eyes of C57BL6-SV129 WT and SPARC-null mice were injected with fluorescent microbeads, which were also passively exposed to freshly enucleated eyes. Confocal and electron microscopy were performed. Percentage effective filtration length (PEFL) was calculated as PEFL = FL/TL {\texttimes} 100\%, where TL = total length and FL = filtration length. IOP was measured by rebound tonometry. RESULTS: Passive microbead affinity for WT and SPARC-null ECM did not differ. Segmental flow was observed in the mouse eye. SPARC-null mice had a 23\% decrease in IOP. PEFL increased in SPARC-null (70.61 {\textpm} 11.36\%) versus WT mice (54.68 {\textpm} 9.95\%, P \&lt; 0.005; n = 11 pairs), and PEFL and IOP were negatively correlated (R(2) = 0.72, n = 10 pairs). Morphologically, TM of high-tracer regions had increased separation between beams compared to low-tracer regions. Collagen fibril diameter decreased in SPARC-null (28.272 nm) versus WT tissue (34.961 nm, P \&lt; 0.0005; n = 3 pairs). CONCLUSIONS: Aqueous outflow in mice is segmental. SPARC-null mice demonstrated a more uniform outflow pattern and decreased collagen fibril diameter. Areas of high flow had less compact juxtacanalicular connective tissue ECM, and IOP was inversely correlated with PEFL. Our data show a correlation between morphology, aqueous outflow, and IOP, indicating a modulatory role of SPARC in IOP regulation.},
	keywords = {Animals, Aqueous Humor, Extracellular Matrix, Fibril-Associated Collagens, Glycoproteins, Intraocular Pressure, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Microscopy, Electron, Microspheres, Osteonectin, Tonometry, Ocular, Trabecular Meshwork, Tumor Suppressor Proteins},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-10950},
	author = {Swaminathan, Swarup S and Oh, Dong-Jin and Kang, Min Hyung and Ren, Ruiyi and Jin, Rui and Gong, Haiyan and Rhee, Douglas J}
}
@article {1528415,
	title = {Automatic processing of gaze movements to quantify gaze scanning behaviors in a driving simulator},
	journal = {Behav Res Methods},
	volume = {53},
	number = {2},
	year = {2021},
	month = {2021 Apr},
	pages = {487-506},
	abstract = {Eye and head movements are used to scan the environment when driving. In particular, when approaching an intersection, large gaze scans to the left and right, comprising head and multiple eye movements, are made. We detail an algorithm called the gaze scan algorithm that automatically quantifies the magnitude, duration, and composition of such large lateral gaze scans. The algorithm works by first detecting lateral saccades, then merging these lateral saccades into gaze scans, with the start and end points of each gaze scan marked in time and eccentricity. We evaluated the algorithm by comparing gaze scans generated by the algorithm to manually marked "consensus ground truth" gaze scans taken from gaze data collected in a high-fidelity driving simulator. We found that the gaze scan algorithm successfully marked 96\% of gaze scans and produced magnitudes and durations close to ground truth. Furthermore, the differences between the algorithm and ground truth were similar to the differences found between expert coders. Therefore, the algorithm may be used in lieu of manual marking of gaze data, significantly accelerating the time-consuming marking of gaze movement data in driving simulator studies. The algorithm also complements existing eye tracking and mobility research by quantifying the number, direction, magnitude, and timing of gaze scans and can be used to better understand how individuals scan their environment.},
	issn = {1554-3528},
	doi = {10.3758/s13428-020-01427-y},
	author = {Swan, Garrett and Goldstein, Robert B and Savage, Steven W and Zhang, Lily and Ahmadi, Aliakbar and Bowers, Alex R}
}
@article {1573130,
	title = {Driving With Hemianopia VII: Predicting Hazard Detection With Gaze and Head Scan Magnitude},
	journal = {Transl Vis Sci Technol},
	volume = {10},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {20},
	abstract = {Purpose: One rehabilitation strategy taught to individuals with hemianopic field loss (HFL) is to make a large blind side scan to quickly identify hazards. However, it is not clear what the minimum threshold is for how large the scan should be. Using driving simulation, we evaluated thresholds (criteria) for gaze and head scan magnitudes that best predict detection safety. Methods: Seventeen participants with complete HFL and 15 with normal vision (NV) drove through 4 routes in a virtual city while their eyes and head were tracked. Participants pressed the horn as soon as they detected a motorcycle (10 per drive) that appeared 54 degrees eccentricity on cross-streets and approached toward the driver. Results: Those with HFL detected fewer motorcycles than those with NV and had worse detection on the blind side than the seeing side. On the blind side, both safe detections and early detections (detections before the hazard entered the intersection) could be predicted with both gaze (safe 18.5 degrees and early 33.8 degrees) and head (safe 19.3 degrees and early 27 degrees) scans. However, on the seeing side, only early detections could be classified with gaze (25.3 degrees) and head (9.0 degrees). Conclusions: Both head and gaze scan magnitude were significant predictors of detection on the blind side, but less predictive on the seeing side, which was likely driven by the ability to use peripheral vision. Interestingly, head scans were as predictive as gaze scans. Translational Relevance: The minimum scan magnitude could be a useful criterion for scanning training or for developing assistive technologies to improve scanning.},
	issn = {2164-2591},
	doi = {10.1167/tvst.10.1.20},
	author = {Swan, Garrett and Savage, Steven W and Zhang, Lily and Bowers, Alex R}
}
@article {313241,
	title = {The alternative complement pathway regulates pathological angiogenesis in the retina},
	journal = {FASEB J},
	volume = {28},
	number = {7},
	year = {2014},
	month = {2014 Jul},
	pages = {3171-82},
	abstract = {A defining feature in proliferative retinopathies is the formation of pathological neovessels. In these diseases, the balance between neovessel formation and regression determines blindness, making the modulation of neovessel growth highly desirable. The role of the immune system in these retinopathies is of increasing interest, but it is not completely understood. We investigated the role of the alternative complement pathway during the formation and resolution of aberrant neovascularization. We used alternative complement pathway-deficient (Fb(-/-)) mice and age- and strain-matched control mice to assess neovessel development and regression in an oxygen-induced retinopathy (OIR) mouse model. In the control mice, we found increased transcription of Fb after OIR treatment. In the Fb(-/-) mice, we prepared retinal flatmounts and identified an increased number of neovessels, peaking at postnatal day 17 (P17; P=0.001). Subjecting human umbilical vein endothelial cells (HUVECs) to low oxygen, mimicking a characteristic of neovessels, decreased the expression of the complement inhibitor Cd55. Finally, using laser capture microdissection (LCM) to isolate the neovessels after OIR, we found decreased expression of Cd55 (P=0.005). Together, our data implicate the alternative complement pathway in facilitating neovessel clearance by down-regulating the complement inhibitor Cd55 specifically on neovessels, allowing for their targeted removal while leaving the established vasculature intact.-Sweigard, J. H., Yanai, R., Gaissert, P., Saint-Geniez, M., Kataoka, K., Thanos, A., Stahl, G. L., Lambris, J. D., Connor, K. M. The alternative complement pathway regulates pathological angiogenesis in the retina.},
	keywords = {Animals, Apoptosis, CD55 Antigens, Cell Proliferation, Cells, Cultured, Complement Pathway, Alternative, Disease Models, Animal, Down-Regulation, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, Oxygen, Retina, Retinal Diseases, Retinal Neovascularization},
	issn = {1530-6860},
	doi = {10.1096/fj.14-251041},
	author = {Sweigard, J Harry and Yanai, Ryoji and Gaissert, Philipp and Saint-Geniez, Magali and Kataoka, Keiko and Thanos, Aristomenis and Stahl, Gregory L and Lambris, John D and Connor, Kip M}
}
@article {503956,
	title = {Inhibition of the alternative complement pathway preserves photoreceptors after retinal injury.},
	journal = {Sci Transl Med},
	volume = {7},
	number = {297},
	year = {2015},
	month = {2015 Jul 22},
	pages = {297ra116},
	abstract = {Degeneration of photoreceptors is a primary cause of vision loss worldwide, making the underlying mechanisms surrounding photoreceptor cell death critical to developing new treatment strategies. Retinal detachment, characterized by the separation of photoreceptors from the underlying retinal pigment epithelium, is a sight-threatening event that can happen in a number of retinal diseases. The detached photoreceptors undergo apoptosis and programmed necrosis. Given that photoreceptors are nondividing cells, their loss leads to irreversible visual impairment even after successful retinal reattachment surgery. To better understand the underlying disease mechanisms, we analyzed innate immune system regulators in the vitreous of human patients with retinal detachment and correlated the results with findings in a mouse model of retinal detachment. We identified the alternative complement pathway as promoting early photoreceptor cell death during retinal detachment. Photoreceptors down-regulate membrane-bound inhibitors of complement, allowing for selective targeting by the alternative complement pathway. When photoreceptors in the detached retina were removed from the primary source of oxygen and nutrients (choroidal vascular bed), the retina became hypoxic, leading to an up-regulation of complement factor B, a key mediator of the alternative pathway. Inhibition of the alternative complement pathway in knockout mice or through pharmacological means ameliorated photoreceptor cell death during retinal detachment. Our current study begins to outline the mechanism by which the alternative complement pathway facilitates photoreceptor cell death in the damaged retina.},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.aab1482},
	author = {Sweigard, J Harry and Matsumoto, Hidetaka and Smith, Kaylee E and Kim, Leo A and Paschalis, Eleftherios I and Okonuki, Yoko and Castillejos, Alexandra and Kataoka, Keiko and Hasegawa, Eiichi and Yanai, Ryoji and Husain, Deeba and Lambris, John D and Vavvas, Demetrios and Miller, Joan W and Connor, Kip M}
}
@article {416961,
	title = {Cataract surgery outcomes at a UK independent sector treatment centre.},
	journal = {Br J Ophthalmol},
	year = {2015},
	month = {2015 Apr 29},
	abstract = {BACKGROUND/AIMS: The goal of this study was to review cataract surgery outcomes at three independent surgery treatment centres established by the UK Specialist Hospitals (UKSH) and to compare these outcomes with recognised benchmarks.

METHODS: All patients who underwent cataract surgery at UKSH between July 2005 and March 2013 were included. Complication rates were obtained using annual quality reports, logbooks kept in operating theatres and outpatient departments, and electronic medical records. Refractive outcomes and biometry results between December 2010 and March 2013 were obtained from electronic medical records. Results were compared with previously published benchmarks.

RESULTS: This study reviewed 20 070 cataract surgeries. UKSH had lower rates of several operative complications compared with the Cataract National Dataset benchmark study. These included choroidal haemorrhage, hyphaema, intraocular lens complications, iris damage from phacoemulsification, nuclear fragment into the vitreous, phacoemulsification wound burn, posterior capsule rupture or vitreous loss or both, vitreous in anterior chamber, and zonular dialysis. UKSH had lower rates of postoperative complications including corneal decompensation, cystoid macular oedema, iris to wound, posterior capsule opacification with yttrium aluminium garnet indicated, raised intraocular pressure, retained soft lens matter, uveitis, vitreous to section, and wound leak. Biometry outcomes at UKSH were significantly better than recently published benchmarks from the National Healthcare Service.

CONCLUSIONS: This is the first large-scale retrospective study of cataract surgery outcomes in the UK independent sector. The results indicate comparable or lower rates for most complications as compared with data collected in a previously published study.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2014-306586},
	author = {Syed, Zeba A and Moayedi, Javad and Mohamedi, Mehdi and Tashter, Jacob and Anthony, Teresa and Celiker, Celadet and Khazen, Georges and Melki, Samir A}
}
@article {1195291,
	title = {Peripheral Endothelial Cell Count Is a Predictor of Disease Severity in Advanced Fuchs Endothelial Corneal Dystrophy},
	journal = {Cornea},
	volume = {36},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {1166-1171},
	abstract = {PURPOSE: In advanced Fuchs endothelial corneal dystrophy (FECD), central endothelial changes do not correlate with disease severity. The peripheral endothelial cell count (ECC) has not been studied as a marker of FECD severity. The goal of this study was to determine the relationship between the peripheral ECC and known clinical markers of FECD in advanced cases. METHODS: Patients with FECD examined between January 1, 2013, and September 1, 2016, by 1 cornea specialist were identified. Medical records from all previous visits were reviewed to include eyes with high-quality central and peripheral in vivo confocal microscopy images performed on the same day as a clinical evaluation. Endothelial photographs were used to perform manual cell counts centrally and peripherally. Clinical grading of FECD from 1 to 4 was performed at the slit-lamp. RESULTS: We identified 154 eyes of 126 patients that met criteria for inclusion. With higher disease grades, central ECC and peripheral ECC decreased, visual acuity worsened, and central corneal thickness (CCT) increased (all P \&lt; 0.05). In patients with advanced disease (defined as either grade 3 or 4, CCT \&gt;700, or central ECC \&lt;350), the peripheral ECC was the best predictor of disease severity and had the highest number of statistically significant correlations with other clinical markers compared with competing variables. CONCLUSIONS: In advanced FECD, severity is best determined by the peripheral ECC compared with the central ECC, visual acuity, clinical disease grade, and CCT. The peripheral ECC should be added to the clinical parameters used to evaluate FECD severity.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001292},
	author = {Syed, Zeba A and Tran, Jennifer A and Jurkunas, Ula V}
}
@article {836981,
	title = {New Ultrasound Biomicroscopy Iris Findings in Juvenile Xanthogranuloma.},
	journal = {J Glaucoma},
	volume = {25},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {e759-60},
	abstract = {We report a case of juvenile xanthogranuloma in a 12-month-old girl presenting with heterochromia, hyphema, and elevated intraocular pressure. This case demonstrates new ultrasound biomicroscopy iris findings of a generalized bumpy iris contour, suggesting diffuse heterogeneous involvement. This imaging finding has not been previously described. Untreated, iris juvenile xanthogranuloma may lead to corneal blood staining, glaucoma, and amblyopia. An understanding of the full range of ultrasound features of juvenile xanthogranuloma expands our appreciation for the clinical findings in this condition.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000443},
	author = {Syed, Zeba A and Chen, Teresa C}
}
@article {1016126,
	title = {Dynamic Intraductal Meibomian Probing: A Modified Approach to the Treatment of Obstructive Meibomian Gland Dysfunction},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2017},
	month = {2017 Feb 17},
	abstract = {PURPOSE: Obstructive meibomian gland dysfunction is a leading cause of ocular morbidity and its treatment remains a challenge. Meibomian gland probing was initially described in 2010. Here, the authors describe a modified technique, dynamic intraductal meibomian probing, which offers several advantages over the traditional approach including increased magnification, greater eyelid stabilization, enhanced anesthesia, and easier identification of gland orifices through the expression of meibum. METHODS: The authors conducted a retrospective chart review of 70 eyelids with treatment-resistant obstructive meibomian gland dysfunction undergoing dynamic intraductal meibomian probing between January 2013 and April 2015. RESULTS: Immediately after the procedure, 91.4\% of cases experienced symptomatic improvement, and no complications were noted. CONCLUSIONS: Dynamic intraductal meibomian probing is an effective and safe treatment for obstructive meibomian gland dysfunction that is resistant to traditional therapies.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000876},
	author = {Syed, Zeba A and Sutula, Francis C}
}
@article {1806596,
	title = {Trends and Sociodemographic Patterns in Keratoconus Management 2015-2020: An American Academy of Ophthalmology IRIS{\textregistered} Registry Analysis},
	journal = {Ophthalmology},
	year = {2024},
	month = {2024 Feb 02},
	abstract = {PURPOSE: Investigate trends in keratoconus (KCN) treatment patterns and diagnosis age between 2015-2020 and evaluate sociodemographic associations with treatment approach. DESIGN: Retrospective cohort study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Patients with a new KCN diagnosis from 2015 to 2020 were identified in the Academy IRIS{\textregistered} Registry (Intelligent Research in Sight). METHODS, INTERVENTION, OR TESTING: Associations between sociodemographic factors and treatment were evaluated using multivariable logistic regression. MAIN OUTCOME MEASURES: Outcomes included percentages and rates of each treatment (either collagen crosslinking [CXL], keratoplasty, or no procedure) from 2015 to 2020, age at diagnosis during this period, and sociodemographic factors associated with treatment type. RESULTS: 66,199 patients with a new diagnosis of KCN were identified. The percentage of patients undergoing CXL increased from 0.05\% in 2015 to 29.5\% in 2020 (P=0.008). The average age (SD) of KCN patients decreased from 44.1 ({\textpm} 16.9) years in 2015 to 39.2 ({\textpm} 16.9) years in 2020 (P\&lt;0.001). In multivariable analyses comparing CXL versus no procedure and keratoplasty versus no procedure, patients undergoing CXL tended to be younger with the odds of having CXL decreasing with increasing age; e.g., comparing CXL and no procedure patients, using ages 0-20 years as reference, the odds ratio (OR) (95\% CI) decreased from 0.62 (0.57-0.67, P\&lt;0.0001) for patients 21-40 years to 0.03 (0.02-0.04, P\&lt;0.0001) for patients older than 60. Males were more likely than females to have CXL (OR=1.31, 95\% CI 1.23-1.40, P\&lt;0.0001) and keratoplasty (OR=1.30, 95\% CI 1.19-1.42, P\&lt;0.0001). Black patients were less likely than White patients to have CXL (OR=0.70, 95\% CI 0.63-0.77, P\&lt;0.0001) and more likely to have keratoplasty (OR=2.24, 95\% CI 2.01-2.50, P\&lt;0.0001). Similarly, Hispanic patients had higher odds of CXL (OR=1.12, 95\% CI 1.00-1.24, P\&lt;0.05) and keratoplasty (OR=1.29, 95\% CI 1.12-1.50, P\&lt;0.001) compared to non-Hispanic patients. CXL and keratoplasty also varied by region and insurance status. CONCLUSIONS: A significant increase in use of CXL was noted from 2015 to 2020. Sociodemographic differences in treatment among KCN patients may reflect differences in access, utilization, or care patterns, and future studies should aim to identify strategies to improve access for all patients.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2024.01.036},
	author = {Syed, Zeba A and Tomaiuolo, Maurizio and Zhang, Qiang and Prajna, Venkatesh and Hyman, Leslie and Rapuano, Christopher J and IRIS{\textregistered} Registry Analytic Center Consortium}
}
@article {1439865,
	title = {Impact of Dry Eye on Visual Acuity and Contrast Sensitivity: Dry Eye Assessment and Management Study},
	journal = {Optom Vis Sci},
	volume = {96},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {387-396},
	abstract = {SIGNIFICANCE: Identification of the association of specific signs of dry eye disease with specific visual function deficits may allow for more targeted approaches to treatment. PURPOSE: The purpose of this study was to explore the association of dry eye signs and symptoms with visual acuity (VA) and contrast sensitivity in the Dry Eye Assessment and Management study. METHODS: Baseline data from participants in the Dry Eye Assessment and Management study were used in this secondary cross-sectional analysis. Standardized procedures were used to obtain results on the Ocular Surface Disease Index (OSDI), high-contrast logMAR VA, contrast sensitivity, tear film debris, tear breakup time (TBUT), corneal fluorescein staining, meibomian gland evaluation, conjunctival lissamine green staining, and Schirmer test scores. Generalized linear models that included age, refractive error status, and cataract status were used to assess the association between VA and contrast sensitivity with OSDI score and each dry eye sign. The Hochberg procedure was used to account for multiple comparisons. RESULTS: Among 487 participants (974 eyes), worse VA was associated with worse mean score on the OSDI vision subscale (39.4 for VA 20/32 or worse vs. 32.4 for VA 20/16 or better; adjusted linear trend, P = .02); scores were not associated with contrast sensitivity. Severe meibomian gland plugging and abnormal secretions were associated with worse mean log contrast sensitivity (1.48 for severe vs. 1.54 for not plugged [P = .04] and 1.49 for obstructed vs. 1.57 for clear [P = .002], respectively). Longer TBUT was associated with better mean log contrast sensitivity (1.57 for TBUT \&gt;5 seconds and 1.51 for TBUT <=2 seconds, P \&lt; .0001). CONCLUSIONS: Worse VA rather than worse contrast sensitivity drives vision-related symptoms in dry eye. Greater tear film instability was associated with worse contrast sensitivity.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001387},
	author = {Szczotka-Flynn, Loretta B and Maguire, Maureen G and Ying, Gui-Shuang and Lin, Meng C and Bunya, Vatinee Y and Dana, Reza and Asbell, Penny A and Dry Eye Assessment and Management (DREAM) Study Research Group}
}
@article {1586150,
	title = {American Academy of Optometry Microbial Keratitis Think Tank},
	journal = {Optom Vis Sci},
	volume = {98},
	number = {3},
	year = {2021},
	month = {2021 Mar 01},
	pages = {182-198},
	abstract = {SIGNIFICANCE: Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. PURPOSE: The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS: Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS: The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. CONCLUSIONS: The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001664},
	author = {Szczotka-Flynn, Loretta B and Shovlin, Joseph P and Schnider, Cristina M and Caffery, Barbara E and Alfonso, Eduardo C and Carnt, Nicole A and Chalmers, Robin L and Collier, Sarah and Jacobs, Deborah S and Joslin, Charlotte E and Kroken, Abby R and Lakkis, Carol and Pearlman, Eric and Schein, Oliver D and Stapleton, Fiona and Tu, Elmer and Willcox, Mark D P}
}
@article {1474211,
	title = {Authors{\textquoteright} Response},
	journal = {Optom Vis Sci},
	volume = {96},
	number = {11},
	year = {2019},
	month = {2019 Nov},
	pages = {892},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001450},
	author = {Szczotka-Flynn, Loretta B and Maguire, Maureen G and Ying, Gui-Shuang and Lin, Meng C and Bunya, Vatinee Y and Dana, Reza and Asbell, Penny A and Dry Eye Assessment and Management (DREAM) Study Research Group}
}
@article {1817256,
	title = {Optical coherence tomography in the management of diabetic macular oedema},
	journal = {Prog Retin Eye Res},
	volume = {98},
	year = {2024},
	month = {2024 Jan},
	pages = {101220},
	abstract = {Diabetic macular oedema (DMO) is the major cause of visual impairment in people with diabetes. Optical coherence tomography (OCT) is now the most widely used modality to assess presence and severity of DMO. DMO is currently broadly classified based on the involvement to the central 1~mm of the macula into non-centre or centre involved DMO (CI-DMO) and DMO can occur with or without visual acuity (VA) loss. This classification forms the basis of management strategies of DMO. Despite years of research on quantitative and qualitative DMO related features assessed by OCT, these do not fully inform physicians of the prognosis and severity of DMO relative to visual function. Having said that, recent research on novel OCT biomarkers development and re-defined classification of DMO show better correlation with visual function and treatment response. This review summarises the current evidence of the association of OCT biomarkers in DMO management and its potential clinical importance in predicting VA and anatomical treatment response. The review also discusses some future directions in this field, such as the use of artificial intelligence to quantify and monitor OCT biomarkers and retinal fluid and identify phenotypes of DMO, and the need for standardisation and classification of OCT biomarkers to use in future clinical trials and clinical practice settings as prognostic markers and secondary treatment outcome measures in the management of DMO.},
	keywords = {Artificial Intelligence, Biomarkers, Diabetes Mellitus, Diabetic Retinopathy, Humans, Macular Edema, Tomography, Optical Coherence, Visual Acuity},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2023.101220},
	author = {Szeto, Simon Kh and Lai, Timothy Y Y and Vujosevic, Stela and Sun, Jennifer K and Sadda, Srinivas R and Tan, Gavin and Sivaprasad, Sobha and Wong, Tien Y and Cheung, Carol Y}
}
@article {1642012,
	title = {A Tensorized Multitask Deep Learning Network for Progression Prediction of Alzheimer{\textquoteright}s Disease},
	journal = {Front Aging Neurosci},
	volume = {14},
	year = {2022},
	month = {2022},
	pages = {810873},
	abstract = {With the advances in machine learning for the diagnosis of Alzheimer{\textquoteright}s disease (AD), most studies have focused on either identifying the subject{\textquoteright}s status through classification algorithms or on predicting their cognitive scores through regression methods, neglecting the potential association between these two tasks. Motivated by the need to enhance the prospects for early diagnosis along with the ability to predict future disease states, this study proposes a deep neural network based on modality fusion, kernelization, and tensorization that perform multiclass classification and longitudinal regression simultaneously within a unified multitask framework. This relationship between multiclass classification and longitudinal regression is found to boost the efficacy of the final model in dealing with both tasks. Different multimodality scenarios are investigated, and complementary aspects of the multimodal features are exploited to simultaneously delineate the subject{\textquoteright}s label and predict related cognitive scores at future timepoints using baseline data. The main intent in this multitask framework is to consolidate the highest accuracy possible in terms of precision, sensitivity, F1 score, and area under the curve (AUC) in the multiclass classification task while maintaining the highest similarity in the MMSE score as measured through the correlation coefficient and the RMSE for all time points under the prediction task, with both tasks, run simultaneously under the same set of hyperparameters. The overall accuracy for multiclass classification of the proposed KTMnet method is 66.85 {\textpm} 3.77. The prediction results show an average RMSE of 2.32 {\textpm} 0.52 and a correlation of 0.71 {\textpm} 5.98 for predicting MMSE throughout the time points. These results are compared to state-of-the-art techniques reported in the literature. A discovery from the multitasking of this consolidated machine learning framework is that a set of hyperparameters that optimize the prediction results may not necessarily be the same as those that would optimize the multiclass classification. In other words, there is a breakpoint beyond which enhancing further the results of one process could lead to the downgrading in accuracy for the other.},
	issn = {1663-4365},
	doi = {10.3389/fnagi.2022.810873},
	author = {Tabarestani, Solale and Eslami, Mohammad and Cabrerizo, Mercedes and Curiel, Rosie E and Barreto, Armando and Rishe, Naphtali and Vaillancourt, David and DeKosky, Steven T and Loewenstein, David A and Duara, Ranjan and Adjouadi, Malek}
}
@article {630571,
	title = {In vivo gene editing in dystrophic mouse muscle and muscle stem cells.},
	journal = {Science},
	year = {2015},
	month = {2015 Dec 31},
	abstract = {Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we develop and test a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored Dystrophin reading frame in myofibers, cardiomyocytes, and muscle stem cells following local or systemic delivery. AAV-Dmd CRISPR-treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.},
	issn = {1095-9203},
	doi = {10.1126/science.aad5177},
	author = {Tabebordbar, Mohammadsharif and Zhu, Kexian and Cheng, Jason K W and Chew, Wei Leong and Widrick, Jeffrey J and Yan, Winston X and Maesner, Claire and Wu, Elizabeth Y and Xiao, Ru and Ran, F Ann and Cong, Le and Zhang, Feng and Vandenberghe, Luk H and Church, George M and Wagers, Amy J}
}
@article {680441,
	title = {Phenotypic transformation of intimal and adventitial lymphatics in atherosclerosis: a regulatory role for soluble VEGF receptor 2.},
	journal = {FASEB J},
	volume = {30},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {2490-9},
	abstract = {The role of lymphatics in atherosclerosis is not yet understood. Here, we investigate lymphatic growth dynamics and marker expression in atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. The prolymphangiogenic growth factor, VEGF-C, was elevated in atherosclerotic aortic walls. Despite increased VEGF-C, we found that adventitial lymphatics regress during the course of formation of atherosclerosis (P \&lt; 0.01). Similar to lymphatic regression, the number of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1(+)) macrophages decreased in the aortic adventitia of apoE(-/-) mice with atherosclerosis (P \&lt; 0.01). Intimal lymphatics in the atherosclerotic lesions exhibited an atypical phenotype, with the expression of podoplanin and VEGF receptor 3 (VEGFR-3) but not of LYVE-1 and prospero homeobox protein 1. In the aortas of atherosclerotic animals, we found markedly increased soluble VEGFR-2. We hypothesized that the elevated soluble VEGFR-2 that was found in the aortas of apoE(-/-) mice with atherosclerosis binds to and diminishes the activity of VEGF-C. This trapping mechanism explains, despite increased VEGF-C in the atherosclerotic aortas, how adventitial lymphatics regress. Lymphatic regression impedes the drainage of lipids, growth factors, inflammatory cytokines, and immune cells. Insufficient lymphatic drainage could thus exacerbate atherosclerosis formation. Our study contributes new insights to previously unknown dynamic changes of adventitial lymphatics. Targeting soluble VEGFR-2 in atherosclerosis may provide a new strategy for the liberation of endogenous VEGF-C and the prevention of lymphatic regression.-Taher, M., Nakao, S., Zandi, S., Melhorn, M. I., Hayes, K. C., Hafezi-Moghadam, A. Phenotypic transformation of intimal and adventitial lymphatics in atherosclerosis: a regulatory role for soluble VEGF receptor 2.},
	issn = {1530-6860},
	doi = {10.1096/fj.201500112},
	author = {Taher, Mahdi and Nakao, Shintaro and Zandi, Souska and Melhorn, Mark I and Hayes, K C and Hafezi-Moghadam, Ali}
}
@article {1586151,
	title = {Application of Artificial Intelligence in the Diagnosis and Management of Corneal Diseases},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {8},
	year = {2021},
	month = {2021 Nov 17},
	pages = {641-648},
	abstract = {Diagnosis and treatment planning in ophthalmology heavily depend on clinical examination and advanced imaging modalities, which can be time-consuming and carry the risk of human error. Artificial intelligence (AI) and deep learning (DL) are being used in different fields of ophthalmology and in particular, when running diagnostics and predicting outcomes of anterior segment surgeries. This review will evaluate the recent developments in AI for diagnostics, surgical interventions, and prognosis of corneal diseases. It also provides a brief overview of the newer AI dependent modalities in corneal diseases.},
	keywords = {Artificial Intelligence, Corneal Diseases, Humans, Ophthalmology},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1893763},
	author = {Tahvildari, Maryam and Singh, Rohan Bir and Saeed, Hajirah N}
}
@article {1478344,
	title = {Low-Dose IL-2 Therapy in Transplantation, Autoimmunity, and Inflammatory Diseases},
	journal = {J Immunol},
	volume = {203},
	number = {11},
	year = {2019},
	month = {2019 Dec 01},
	pages = {2749-2755},
	abstract = {Regulatory T cells (Tregs) play a central role in the induction and maintenance of immune homeostasis and self-tolerance. Tregs constantly express the high-affinity receptor to IL-2. IL-2 is a pleiotropic cytokine and a key survival factor for Tregs. It maintains Tregs{\textquoteright} suppressive function by promoting Foxp3 expression and subsequent production of immunoregulatory cytokines. Administration of low-dose IL-2 is shown to be a promising approach to prevent allograft rejection and to treat autoimmune and inflammatory conditions in experimental models. The combination of IL-2 with its mAb (JES6-1) has also been shown to increase the of IL-2 and further enhance Treg frequencies and function. Low-dose IL-2 therapy has been used in several clinical trials to treat conditions such as hepatitis C vasculitis, graft-versus-host disease, type 1 diabetes, and systemic lupus erythematosus. In this paper, we summarize our findings on low-dose IL-2 treatment in corneal allografting and review recent studies focusing on the use of low-dose IL-2 in transplantation, autoimmunity, and other inflammatory conditions. We also discuss potential areas of further investigation with the aim to optimize current low-dose IL-2 regimens.},
	issn = {1550-6606},
	doi = {10.4049/jimmunol.1900733},
	author = {Tahvildari, Maryam and Dana, Reza}
}
@article {669336,
	title = {In Vivo Expansion of Regulatory T Cells by Low-Dose Interleukin-2 Treatment Increases Allograft Survival in Corneal Transplantation.},
	journal = {Transplantation},
	volume = {100},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {525-32},
	abstract = {BACKGROUND: Corneal allograft survival dramatically decreases in hosts with inflamed or vascularized recipient beds. We have previously shown that in rejected corneal allografts regulatory T cells (Treg) demonstrate diminished Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2 selectively expands Treg and has been proposed for the treatment of autoimmune diseases. In this study, we investigated the effect of low-dose IL-2 administration on Treg function and corneal allograft survival. METHODS: Allogeneic corneal transplantation was performed on inflamed host beds. Low-dose systemic IL-2 was administered starting 3 days before grafting until 6 weeks after transplantation. Frequencies of Treg and their immunosuppressive function and antigen specificity were assessed using flow cytometry, in vitro proliferation assays, and adoptive transfer experiments. Frequencies of effector T cells (Teff) and graft infiltrating immune cells were measured at 2 weeks posttransplantation. Long-term allograft survival was evaluated for up to 9 weeks using Kaplan-Meier survival analysis. RESULTS: Treatment with low-dose IL-2 significantly increased frequencies of CD4CD25Foxp3 Treg and their immunosuppressive function. It also suppressed alloimmune response as shown by the decreased CD4 IFNγ T cell frequencies and graft infiltration of CD45 and CD4 cells. Clinical evaluation of the grafts showed significant improvement in long-term corneal allograft survival in the IL-2 treated group compared with controls. CONCLUSIONS: Our study is the first to report that treatment with low-dose IL-2 increases survival of corneal allografts. We propose that IL-2-mediated Treg expansion can be an effective tool to prevent alloimmunity and to improve long-term allograft survival in transplantation.},
	issn = {1534-6080},
	doi = {10.1097/TP.0000000000001044},
	author = {Tahvildari, Maryam and Omoto, Masahiro and Chen, Yihe and Emami-Naeini, Parisa and Inomata, Takenori and Dohlman, Thomas H and Kaye, Abigail E and Chauhan, Sunil K and Dana, Reza}
}
@article {1059836,
	title = {Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 Apr 20},
	pages = {971},
	abstract = {Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds. Treatment of donor corneas with interleukin-10 (IL-10) and transforming growth factor-β1 (TGFβ1) altered the phenotype and function of tissue-residing APCs. Transplantation of these tolAPC-enriched corneas decreased frequencies of interferon gamma (IFNγ)(+) effector T cells (Teffs), as well as allosensitization in the hosts, diminished graft infiltration of CD45(+) and CD4(+) cells, and significantly improved corneal allograft survival compared to saline-injected controls. These data provide a novel approach for tolAPC-based immunotherapy in transplantation by direct cytokine conditioning of the donor tissue.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-01065-z},
	author = {Tahvildari, Maryam and Emami-Naeini, Parisa and Omoto, Masahiro and Mashaghi, Alireza and Chauhan, Sunil K and Dana, Reza}
}
@article {280791,
	title = {Correlation and Agreement Between Cirrus HD-OCT "RNFL Thickness Map" and Scan Circle Retinal Nerve Fiber Layer Thickness Measurements.},
	journal = {J Glaucoma},
	volume = {25},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {208-16},
	abstract = {PURPOSE: To evaluate the correlation and agreement between optical coherence tomography (Cirrus HD-OCT) retinal nerve fiber layer (RNFL) thickness map and scan circle RNFL thickness measurements. METHODS: ImageJ and custom Perl scripts were used to derive RNFL thickness measurements from RNFL thickness maps of optic disc scans of healthy and glaucomatous eyes. Average, quadrant, and clock-hour RNFL thickness of the map, and RNFL thickness of the areas inside/outside the scan circle were obtained. Correlation and agreement between RNFL thickness map and scan circle RNFL thickness measurements were evaluated using R and Bland-Altman plots, respectively. RESULTS: A total of 104 scans from 26 healthy eyes and 120 scans from 30 glaucomatous eyes were analyzed. RNFL thickness map and scan circle measurements were highly reproducible (eg, in healthy eyes, average RNFL thickness coefficients of variation were 2.14\% and 2.52\% for RNFL thickness map and scan circle, respectively) and highly correlated (0.55<=R<=0.98). In general, the scan circle provided greater RNFL thickness than the RNFL thickness map in corresponding sectors and the differences tended to increase as RNFL thickness increased. The width of the 95\% limits of agreement ranged between 5.28 and 36.80 μm in healthy eyes, and between 11.69 and 42.89 μm in glaucomatous eyes. CONCLUSIONS: Despite good correlation between RNFL thickness map and scan circle measurements, agreement was generally poor, suggesting that RNFL thickness assessment over the entire scan area may provide additional clinically relevant information to the conventional scan circle analysis. In the absence of available measurements from the entire peripapillary region, the RNFL thickness maps can be used to investigate localized RNFL thinning in areas not intercepted by the scan circle.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000149},
	author = {Taibbi, Giovanni and Kim, James D and Bakir, Belal H and Shenoy, Sudhir R and Pearce, William A and Taroyan, Gregory and Birdsong, Orry C and Loucks, Emma K and Vizzeri, Gianmarco}
}
@article {1653570,
	title = {The whisking oscillator circuit},
	journal = {Nature},
	volume = {609},
	number = {7927},
	year = {2022},
	month = {2022 09},
	pages = {560-568},
	abstract = {Central\&nbsp;oscillators are primordial neural circuits that generate and control rhythmic movements1,2. Mechanistic understanding of these circuits requires genetic identification of the oscillator neurons and their synaptic connections to enable targeted electrophysiological recording and causal manipulation during behaviours. However, such targeting remains a challenge with mammalian systems. Here we delimit the oscillator circuit that drives rhythmic whisking-a motor action that is central to foraging and active sensing in rodents3,4. We found that the whisking oscillator consists of parvalbumin-expressing inhibitory neurons located in the vibrissa intermediate reticular nucleus (vIRtPV) in the brainstem. vIRtPV neurons receive descending excitatory inputs and form recurrent inhibitory connections among themselves. Silencing vIRtPV neurons eliminated rhythmic whisking and resulted in sustained vibrissae protraction. In vivo recording of opto-tagged vIRtPV neurons in awake mice showed that these cells spike tonically when animals are at rest, and transition to rhythmic bursting at the onset of whisking, suggesting that rhythm generation is probably the result of network dynamics, as opposed to intrinsic cellular properties. Notably, ablating inhibitory synaptic inputs to vIRtPV neurons quenched their rhythmic bursting, impaired the tonic-to-bursting transition and abolished regular whisking. Thus, the whisking oscillator is an all-inhibitory network and recurrent synaptic inhibition has a key role in its rhythmogenesis.},
	keywords = {Animals, Brain Stem, Mice, Movement, Neural Inhibition, Neural Pathways, Neurons, Parvalbumins, Periodicity, Rest, Synapses, Vibrissae, Wakefulness},
	issn = {1476-4687},
	doi = {10.1038/s41586-022-05144-8},
	author = {Takatoh, Jun and Prevosto, Vincent and Thompson, P M and Lu, Jinghao and Chung, Leeyup and Harrahill, Andrew and Li, Shun and Zhao, Shengli and He, Zhigang and Golomb, David and Kleinfeld, David and Wang, Fan}
}
@article {1789121,
	title = {Concurrence of Ocular Cicatricial Pemphigoid in Chronic Ocular Graft-Versus-Host Disease},
	journal = {Cornea},
	volume = {43},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {387-390},
	abstract = {PURPOSE: The aim of this study was to report a series of 3 patients with ocular graft-versus-host disease (oGVHD) with progressive cicatricial conjunctival changes who were diagnosed with ocular cicatricial pemphigoid (OCP) after conjunctival biopsy. METHODS: This study was a retrospective case series. RESULTS: Three patients who received hematopoietic stem cell transplantation for hematologic malignancies developed oGVHD and subsequently were diagnosed with OCP. Case 1 was a 73-year-old woman with oGVHD who developed symblepharon and showed positive IgA, IgG, and C3 staining of the basement membrane zone (BMZ) on conjunctival biopsy, consistent with OCP. She was systemically treated with tacrolimus and prednisone with resolution of conjunctival inflammation. Case 2 was a 68-year-old man with oGVHD who developed symblepharon, severe dry eye, and corneal epithelial defect. An initial conjunctival biopsy was negative, but a repeat biopsy performed 10 years later showed positive BMZ IgA and IgG staining. Healing of the epithelial defect was achieved after treatment with high-dose systemic cyclosporine. Case 3 was a 75-year-old woman with oGVHD who had a nonhealing corneal epithelial defect and symblepharon with positive IgA BMZ staining on conjunctival biopsy, consistent with OCP. The patient responded well to methotrexate with healing of the epithelial defect. CONCLUSIONS: Although low-grade conjunctival fibrotic changes may be observed in chronic oGVHD, development of severe and progressive cicatricial changes, including symblepharon formation, should prompt consideration of biopsy to rule out concurrent OCP, the management of which differs from that of oGVHD.},
	keywords = {Aged, Female, Graft vs Host Disease, Humans, Immunoglobulin A, Immunoglobulin G, Male, Pemphigoid, Benign Mucous Membrane, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003386},
	author = {Taketani, Yukako and Dehghani, Shima and Sinha, Shruti and Freitag, Suzanne K and Papaliodis, George and Foster, Stephen and Dohlman, Thomas H and Dana, Reza}
}
@article {1532368,
	title = {Restoration of Regulatory T-Cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor},
	journal = {Am J Pathol},
	volume = {190},
	number = {9},
	year = {2020},
	month = {2020 09},
	pages = {1859-1866},
	abstract = {Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in\&nbsp;vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in\&nbsp;vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity.},
	keywords = {Animals, Dry Eye Syndromes, Female, Mice, Mice, Inbred C57BL, Neurokinin-1 Receptor Antagonists, Receptors, Neurokinin-1, T-Lymphocytes, Regulatory},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.05.011},
	author = {Taketani, Yukako and Marmalidou, Anna and Dohlman, Thomas H and Singh, Rohan Bir and Amouzegar, Afsaneh and Chauhan, Sunil K and Chen, Yihe and Dana, Reza}
}
@article {1363212,
	title = {AMP-dependent kinase inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis by suppressing the dissociation between c-Abl and Prdx1 proteins in endothelial cells},
	journal = {J Biol Chem},
	volume = {288},
	number = {28},
	year = {2013},
	month = {2013 Jul 12},
	pages = {20581-91},
	abstract = {Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPKα subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1.},
	keywords = {Albumins, Aminoimidazole Carboxamide, AMP-Activated Protein Kinases, Blotting, Western, Caveolin 1, Cells, Cultured, Dipyridamole, Endocytosis, Enzyme Activation, Human Umbilical Vein Endothelial Cells, Humans, Hydrogen Peroxide, Isoenzymes, Microscopy, Confocal, Oxidants, Oxidative Stress, Peroxiredoxins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-abl, Ribonucleotides, RNA Interference, Tubercidin},
	issn = {1083-351X},
	doi = {10.1074/jbc.M113.460832},
	author = {Takeuchi, Kimio and Morizane, Yuki and Kamami-Levy, Cynthia and Suzuki, Jun and Kayama, Maki and Cai, Wenyi and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1351200,
	title = {EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay},
	journal = {PLoS One},
	volume = {9},
	number = {3},
	year = {2014},
	month = {2014},
	pages = {e91849},
	abstract = {EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization.},
	keywords = {Animals, Biological Assay, Endothelial Cells, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Gene Knockdown Techniques, In Vitro Techniques, Mice, Inbred C57BL, Neovascularization, Physiologic, Neuropilin-1, Phosphorylation, Proteins, Proto-Oncogene Proteins c-akt, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0091849},
	author = {Takeuchi, Kimio and Yanai, Ryoji and Kumase, Fumiaki and Morizane, Yuki and Suzuki, Jun and Kayama, Maki and Brodowska, Katarzyna and Nakazawa, Mitsuru and Miller, Joan W and Connor, Kip M and Vavvas, Demetrios G}
}
@article {1817316,
	title = {Selective Laser Trabeculoplasty for the Treatment of Glaucoma: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {131},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {37-47},
	abstract = {PURPOSE: To review the current published literature for high-quality studies on the use of selective laser trabeculoplasty (SLT) for the treatment of glaucoma. This is an update of the Ophthalmic Technology Assessment titled, "Laser Trabeculoplasty for Open-Angle Glaucoma," published in November~2011.

METHODS: Literature searches in the PubMed database in March 2020, September 2021, August 2022, and March 2023 yielded 110 articles. The abstracts of these articles were examined to include those written since November 2011 and to exclude reviews and non-English articles. The panel reviewed 47 articles in full text, and 30 were found to fit the inclusion criteria. The panel methodologist assigned a level I rating to 19 studies and a level II rating to 11 studies.

RESULTS: Data in the level I studies support the long-term effectiveness of SLT as primary treatment or as a supplemental therapy to glaucoma medications for patients with open-angle glaucoma. Several level I studies also found that SLT and argon laser trabeculoplasty (ALT) are equivalent in terms of safety and long-term efficacy. Level I evidence indicates that perioperative corticosteroid and nonsteroidal anti-inflammatory drug eye drops do not hinder the intraocular pressure (IOP)-lowering effect of SLT treatment. The impact of these eye drops on lowering IOP differed in various studies. No level I or II studies exist that determine the ideal power settings for SLT.

CONCLUSIONS: Based on level I evidence, SLT is an effective long-term option for the treatment of open-angle glaucoma and is equivalent to ALT. It can be used as either a primary intervention, a replacement for medication, or an additional therapy with glaucoma medications.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Glaucoma, Glaucoma, Open-Angle, Humans, Lasers, Ophthalmic Solutions, Ophthalmology, Trabecular Meshwork, Trabeculectomy, United States},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.07.029},
	author = {Takusagawa, Hana L and Hoguet, Ambika and Sit, Arthur J and Rosdahl, Jullia A and Chopra, Vikas and Ou, Yvonne and Richter, Grace and Kim, Stephen J and WuDunn, Darrell}
}
@article {1435417,
	title = {Swept-Source OCT for Evaluating the Lamina Cribrosa: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {126},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {1315-1323},
	abstract = {PURPOSE: To review the published literature on the use of swept-source (SS) OCT for evaluating the lamina cribrosa in glaucoma. METHODS: A PubMed and Cochrane Library literature search initially conducted on March 3, 2017, and updated on June 26, 2018, yielded a total of 64 articles. Articles that were reviews or that were not published in English were excluded, and 29 were found to fit the inclusion criteria. The panel methodologist then assigned a level of evidence rating to each study. Fifteen studies were rated level III, 14 studies were rated level II, and no studies were rated level I. RESULTS: Different aspects of the lamina cribrosa were studied using SS-OCT, including the anterior lamina cribrosa curvature, anterior lamina cribrosa depth, anterior lamina cribrosa insertions, laminar thickness, focal lamina cribrosa defects (FLCDs), and lamina cribrosa microarchitecture. In general, imaging of the anterior lamina can be achieved reliably, although shadowing from blood vessels at the neuroretinal rim remains an issue. Imaging of the posterior lamina can be achieved with varying levels of success. In glaucoma, there is posterior migration of the anterior lamina cribrosa insertions as well as increased thinning and posterior curvature of the lamina cribrosa. Focal lamina cribrosa defects appear more commonly in glaucoma, and this may hint at the pathogenesis of axonal damage. In addition, there may be remodeling of the microarchitecture of the lamina, resulting in more variable laminar pores. There are limited studies comparing SS-OCT with spectral-domain (SD) OCT with regard to imaging of the lamina, but the difference in image quality between enhanced depth imaging (EDI) with SD-OCT and SS-OCT seems minimal. CONCLUSIONS: Imaging of the lamina cribrosa using SS-OCT has demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. The diagnostic utility of SS-OCT for lamina cribrosa imaging is promising, but standardized nomenclature, automated measurements, and longitudinal studies with larger and more diverse sample sizes are needed.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.03.044},
	author = {Takusagawa, Hana L and Hoguet, Ambika and Junk, Anna K and Nouri-Mahdavi, Kouros and Radhakrishnan, Sunita and Chen, Teresa C}
}
@article {280866,
	title = {Vascular Engorgement of Lacrimal Gland Associated With Port-Wine Stain.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {4},
	year = {2016},
	month = {2016 Jul-Aug},
	pages = {e92-4},
	abstract = {Port-wine stains are congenital dermal capillary malformations that typically involve the head and neck. While most of them are isolated malformations, they have been associated with other vascular findings, including conjunctival, episcleral, and choroidal hemangiomas. They have also been associated with the phakomatosis Sturge-Weber syndrome, characterized by parieto-occipital, leptomeningeal, and ocular choroidal vascular malformations. However, vascular engorgement of the lacrimal gland has not been previously reported in association with port-wine stains. The authors present a case of a 52-year-old man with a long-standing and isolated right periorbital port-wine stain referred for lacrimal gland enlargement on CT scan. He was found to have asymptomatic right lacrimal gland vascular engorgement, which was radiographically stable over a period of 5 years.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000271},
	author = {Talcott, Katherine E and Lee, Nahyoung Grace and Freitag, Suzanne K}
}
@article {1580513,
	title = {Exudative hemorrhagic retinopathy related to all-trans retinoic acid differentiation syndrome in a patient with acute promyelocytic leukemia},
	journal = {Int J Ophthalmol},
	volume = {14},
	number = {2},
	year = {2021},
	month = {2021},
	pages = {323-325},
	issn = {2222-3959},
	doi = {10.18240/ijo.2021.02.22},
	author = {Tam, Emily K and Ness, Steven and Peeler, Crandall E}
}
@article {1635642,
	title = {ARHGEF-10 gene mutation presenting as orbital inflammatory syndrome},
	journal = {BMJ Case Rep},
	volume = {15},
	number = {3},
	year = {2022},
	month = {2022 Mar 08},
	abstract = {Rho guanine nucleotide exchange factor 10 (ARHGEF-10) is a RHO GTPase that has a role for neural morphogenesis, however its effect on the eyes remains unknown. Here, we report a 44-year-old man who presented with eyelid swelling along with a history of bilateral hand contractures, high-arched feet and muscle wasting, who was found to have an ARHGEF-10 mutation. Neuroimaging was significant for numerous nerve-based cystic abnormalities in the bilateral orbits and throughout the neuraxis, and an orbital biopsy revealed S-100 and SOX-10 positive lesion consistent with pseudocysts. While the role of ARHGEF-10 remains unclear, further research is warranted to further describe its clinical manifestations.},
	keywords = {Adult, Eye, Eye Diseases, Humans, Inflammation, Male, Mutation, Orbit, Rho Guanine Nucleotide Exchange Factors, Syndrome},
	issn = {1757-790X},
	doi = {10.1136/bcr-2021-245475},
	author = {Tam, Emily K and Laver, Nora V and Thakore-James, Manisha and Mooney, Michael A and Daly, Mary K and Lefebvre, Daniel R}
}
@article {1638556,
	title = {Etiology and outcomes of childhood glaucoma at a tertiary referral center},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Apr 08},
	abstract = {PURPOSE: To describe the etiology, clinical features, and outcomes for a large contemporary cohort of children presenting with glaucoma at a tertiary referral center. METHODS: The medical records of patients presenting to Boston Children{\textquoteright}s Hospital from January 2014 to July 2019 with a diagnosis of childhood glaucoma were retrospectively reviewed. Data regarding etiology, treatment, and visual and anatomic outcomes were collected; visual acuity outcomes were analyzed by laterality and diagnosis categories, using the Childhood Glaucoma Research Network (CGRN) classifications. RESULTS: A total of 373 eyes of 246 patients (51\% males) diagnosed with glaucoma before 18 years of age were identified. Mean follow-up was 7.04 {\textpm} 5.61 years; 137 cases were bilateral. The mean age at diagnosis was 4.55 {\textpm} 5.20 years. The most common diagnoses were glaucoma following cataract surgery (GFCS, 36.5\%) and primary congenital glaucoma (PCG, 29.0\%). Overall, 164 eyes (44.0\%) underwent at least one glaucoma surgery. Intraocular pressure (IOP) was <=21 mm Hg with or without glaucoma medications in 300 eyes (80.4\%) at the last follow-up visit. Poor final best-corrected visual acuity (<=20/200) was found in 110 eyes; patients with poor final visual acuity tended to have poor visual acuity at presentation. The most common reason for poor vision was amblyopia. Uncontrolled IOP was an uncommon cause for vision loss. CONCLUSIONS: Childhood glaucoma can be challenging to manage, but poor vision usually results from amblyopia or presence of other ocular abnormalities or syndromes rather than glaucomatous optic neuropathy.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2021.12.009},
	author = {Tam, Emily K and Elhusseiny, Abdelrahman M and Shah, Ankoor S and Mantagos, Iason S and VanderVeen, Deborah K}
}
@article {1483611,
	title = {Glaucoma screening: where are we and where do we need to go?},
	journal = {Curr Opin Ophthalmol},
	volume = {31},
	number = {2},
	year = {2020},
	month = {2020 Mar},
	pages = {91-100},
	abstract = {PURPOSE OF REVIEW: Current recommendations for glaucoma screening are decidedly neutral. No studies have yet documented improved long-term outcomes for individuals who undergo glaucoma screening versus those who do not. Given the long duration that would be required to detect a benefit, future studies that may answer this question definitively are unlikely. Nevertheless, advances in artificial intelligence and telemedicine will lead to more effective screening at lower cost. With these new technologies, additional research is needed to determine the costs and benefits of screening for glaucoma. RECENT FINDINGS: Using optic disc photographs and/or optical coherence tomography, deep learning systems appear capable of diagnosing glaucoma more accurately than human graders. Eliminating the need for expert graders along with better technologies for remote imaging of the ocular fundus will allow for less expensive screening, which could enable screening of individuals with otherwise limited healthcare access. In India and China, where most glaucoma remains undiagnosed, glaucoma screening was recently found to be cost-effective. SUMMARY: Recent advances in artificial intelligence and telemedicine have the potential to increase the accuracy, reduce the costs, and extend the reach of screening. Further research into implementing these technologies in glaucoma screening is required.},
	keywords = {Artificial Intelligence, Cost-Benefit Analysis, Deep Learning, Diagnostic Techniques, Ophthalmological, Economics, Medical, Glaucoma, Humans, Telemedicine, Tomography, Optical Coherence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000649},
	author = {Tan, Nicholas Y Q and Friedman, David S and Stalmans, Ingeborg and Ahmed, Iqbal Ike K and Sng, Chelvin C A}
}
@article {1323942,
	title = {The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease},
	journal = {Ocul Surf},
	volume = {16},
	number = {4},
	year = {2018},
	month = {2018 Oct},
	pages = {470-477},
	abstract = {PURPOSE: In this study, we examine the expression of corneal epithelium-derived thrombospondin-1 (TSP-1) and its immunomodulatory functions in a validated murine model of dry eye disease (DED). METHODS: DED was induced in female C57BL/6 using a controlled environment chamber (CEC) for 14 days. mRNA and protein expression of TSP-1 by corneal epithelial cells was quantified using real-time PCR and flow cytometry. Corneal epithelial cells from either na{\"\i}ve or DED mice were cultured with bone marrow derived dendritic cells (BMDCs) in the presence of IFNγ for 48 h, and BMDC expression of MHC-II and CD86 was determined using flow cytometry. Next, either recombinant TSP-1 or anti-TSP-1 antibody was added to the co-culture, and BMDC expression of above activation markers was evaluated. Finally, either DED mice were topically treated with either recombinant TSP-1 or human serum albumin (HSA), and maturation of corneal DCs, expression of inflammatory cytokines, and DED severity were investigated. RESULTS: mRNA expression of TSP-1 by the corneal epithelium was upregulated in DED. Corneal epithelial cells derived from mice with DED demonstrated an enhanced capacity in suppressing BMDC expression of MHC-II and CD86 relative to wild type mice, and this effect was abrogated by TSP-1 blockade and potentiated by recombinant TSP-1. Finally, topical application of recombinant TSP-1 significantly suppressed corneal DC maturation and mRNA expression of pro-inflammatory cytokines, and ameliorated disease severity in mice with DED. CONCLUSIONS: Our study elucidates the function of epithelium-derived TSP-1 in inhibiting DC maturation and shows its translational potential to limit corneal epitheliopathy in DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.07.005},
	author = {Tan, Xuhua and Chen, Yihe and Foulsham, William and Amouzegar, Afsaneh and Inomata, Takenori and Liu, Yizhi and Chauhan, Sunil K and Dana, Reza}
}
@article {1645476,
	title = {POSTERIOR VITREOUS DETACHMENT STATUS AS A PREDICTIVE FACTOR FOR OUTCOMES OF VITRECTOMY FOR DIABETIC VITREOUS HEMORRHAGE},
	journal = {Retina},
	volume = {42},
	number = {6},
	year = {2022},
	month = {2022 06 01},
	pages = {1103-1110},
	abstract = {PURPOSE: The purpose of this study was to evaluate the prognostic utility of the degree of vitreous attachment for predicting outcomes of vitrectomy for nonclearing vitreous hemorrhage associated with proliferative diabetic retinopathy. METHODS: Medical records of patients who underwent primary vitrectomy for dense nonclearing vitreous hemorrhage secondary to proliferative diabetic retinopathy were examined retrospectively. Eyes were divided into four groups based on the intraoperatively assessed stage of posterior vitreous detachment (PVD), ranging from Stage 0/1 (complete or near-complete vitreoretinal adhesion) to Stage 4 (complete PVD). RESULTS: Overall, 136 eyes (117 patients) were included. In comparison with eyes with a partial or complete PVD (Stages 2-4), eyes with no PVD (Stage 0/1) had a higher incidence of postoperative hypotony (8\%, P = 0.03) and traction retinal detachment (27\%, P = 0.002), an increased rate of repeat vitrectomy (49\%, P = 0.04), and poorer best-corrected visual acuity at 6 months and 1 year postoperatively (P = 0.04 and P = 0.01, respectively). Presence of a complete PVD at baseline was independently associated with improved postoperative vision at 6 months (P = 0.04). CONCLUSION: More extensive vitreoretinal adhesion is associated with higher rates of reoperation and poorer visual outcomes after vitrectomy for dense nonclearing vitreous hemorrhage associated with proliferative diabetic retinopathy. Preoperative determination of PVD status using B-scan ultrasonography may be useful for predicting anatomical and functional outcomes after vitrectomy in these patients.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Humans, Retrospective Studies, Visual Acuity, Vitrectomy, Vitreous Detachment, Vitreous Hemorrhage},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003453},
	author = {Tandias, Rachel and Lemire, Colin A and Palvadi, Karishma and Arroyo, Jorge G}
}
@article {468956,
	title = {African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {6},
	year = {2015},
	month = {2015 Jun 1},
	pages = {3999-4005},
	abstract = {PURPOSE: To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). METHODS: Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. RESULTS: In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95\% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95\% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. CONCLUSIONS: In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic \&gt; 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-16674},
	author = {Tandon, Arti and Chen, Ching J and Penman, Alan and Hancock, Heather and James, Maurice and Husain, Deeba and Andreoli, Christopher and Li, Xiaohui and Kuo, Jane Z and Idowu, Omolola and Riche, Daniel and Papavasilieou, Evangelia and Brauner, Stacey and Smith, Sataria O and Hoadley, Suzanne and Richardson, Cole and Kieser, Troy and Vazquez, Vanessa and Chi, Cheryl and Fernandez, Marlene and Harden, Maegan and Cotch, Mary Frances and Siscovick, David and Taylor, Herman A and Wilson, James G and Reich, David and Wong, Tien Y and Klein, Ronald and Klein, Barbara E K and Rotter, Jerome I and Patterson, Nick and Sobrin, Lucia}
}
@article {726241,
	title = {Detection and manipulation of live antigen-expressing cells using conditionally stable nanobodies.},
	journal = {Elife},
	volume = {5},
	year = {2016},
	month = {2016 May 20},
	abstract = {The ability to detect and/or manipulate specific cell populations based upon the presence of intracellular protein epitopes would enable many types of studies and applications. Protein binders such as nanobodies (Nbs) can target untagged proteins (antigens) in the intracellular environment. However, genetically expressed protein binders are stable regardless of antigen expression, complicating their use for applications that require cell-specificity. Here, we created a conditional system in which the stability of an Nb depends upon an antigen of interest. We identified Nb framework mutations that can be used to rapidly create destabilized Nbs. Fusion of destabilized Nbs to various proteins enabled applications in living cells, such as optogenetic control of neural activity in specific cell types in the mouse brain, and detection of HIV-infected human cells by flow cytometry. These approaches are generalizable to other protein binders, and enable the rapid generation of single-polypeptide sensors and effectors active in cells expressing specific intracellular proteins.},
	issn = {2050-084X},
	doi = {10.7554/eLife.15312},
	author = {Tang, Jonathan C Y and Drokhlyansky, Eugene and Etemad, Behzad and Rudolph, Stephanie and Guo, Binggege and Wang, Sui and Ellis, Emily G and Li, Jonathan Z and Cepko, Constance L}
}
@article {1323943,
	title = {Vitamin D and its pathway genes in myopia: systematic review and meta-analysis},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {8-17},
	abstract = {OBJECTIVE: To conduct a systematic review and meta-analysis of the association of blood vitamin D (25-hydroxyvitamin D, 25(OH)D) concentration and vitamin D pathway genes with myopia. METHODS: We searched the MEDLINE and EMBASE databases for studies published up to 29 January 2018. Cross-sectional or cohort studies which evaluated the blood 25(OH)D concentration, blood 25(OH)D3 concentration or vitamin D pathway genes, in relation to risk of myopia or refractive errors were included. Standard mean difference (SMD) of blood 25(OH)D concentrations between the myopia and non-myopia groups was calculated. The associations of blood 25(OH)D concentrations and polymorphisms in vitamin D pathway genes with myopia using summary ORs were evaluated. RESULTS: We summarised seven studies involving 25 008 individuals in the meta-analysis. The myopia group had lower 25(OH)D concentration than the non-myopia group (SMD=-0.27 nmol/L, p=0.001). In the full analysis, the risk of myopia was inversely associated with blood 25(OH)D concentration after adjusting for sunlight exposure or time spent outdoors (adjusted odds ratio (AOR)=0.92 per 10 nmol/L, p\&lt;0.0001). However, the association was not statistically significant for the \&lt;18 years subgroup (AOR=0.91 per 10 nmol/L, p=0.13) and was significant only for 25(OH)D3 (likely to be mainly sunlight derived), but not total 25(OH)D (AOR=0.93 per 10 nmol/L, p=0.00007; AOR=0.91 per 10 nmol/L, p=0.15). We analysed four single nucleotide polymorphisms in the VDR gene from two studies; there was no significant association with myopia. CONCLUSIONS: Lower 25(OH)D is associated with increased risk of myopia; the lack of a genetic association suggests that 25(OH)D level may be acting as a proxy for time outdoors.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-312159},
	author = {Tang, Shu Min and Lau, Tiffany and Rong, Shi Song and Yazar, Seyhan and Chen, Li Jia and Mackey, David A and Lucas, Robyn M and Pang, Chi Pui and Yam, Jason C}
}
@article {669241,
	title = {f-divergence cutoff index to simultaneously identify differential expression in the integrated transcriptome and proteome.},
	journal = {Nucleic Acids Res},
	volume = {44},
	number = {10},
	year = {2016},
	month = {2016 Jun 2},
	pages = {e97},
	abstract = {The ability to integrate {\textquoteright}omics{\textquoteright} (i.e. transcriptomics and proteomics) is becoming increasingly important to the understanding of regulatory mechanisms. There are currently no tools available to identify differentially expressed genes (DEGs) across different {\textquoteright}omics{\textquoteright} data types or multi-dimensional data including time courses. We present fCI (f-divergence Cut-out Index), a model capable of simultaneously identifying DEGs from continuous and discrete transcriptomic, proteomic and integrated proteogenomic data. We show that fCI can be used across multiple diverse sets of data and can unambiguously find genes that show functional modulation, developmental changes or misregulation. Applying fCI to several proteogenomics datasets, we identified a number of important genes that showed distinctive regulation patterns. The package fCI is available at R Bioconductor and http://software.steenlab.org/fCI/.},
	issn = {1362-4962},
	doi = {10.1093/nar/gkw157},
	author = {Tang, Shaojun and Hemberg, Martin and Cansizoglu, Ertugrul and Belin, Stephane and Kosik, Kenneth and Kreiman, Gabriel and Steen, Hanno and Steen, Judith}
}
@article {314211,
	title = {Spatiotemporal dynamics underlying object completion in human ventral visual cortex},
	journal = {Neuron},
	volume = {83},
	number = {3},
	year = {2014},
	month = {2014 Aug 06},
	pages = {736-48},
	abstract = {Natural vision often involves recognizing objects from partial information. Recognition of objects from parts presents a significant challenge for theories of vision because it requires spatial integration and extrapolation from prior knowledge. Here we recorded intracranial field potentials of 113 visually selective electrodes from epilepsy patients in response to whole and partial objects. Responses along the ventral visual stream, particularly the inferior occipital and fusiform gyri, remained selective despite showing only 9\%-25\% of the object areas. However, these visually selective signals emerged \~{}100\&nbsp;ms later for partial versus whole objects. These processing delays were particularly pronounced in higher visual areas within the ventral stream. This latency difference persisted when controlling for changes in contrast, signal amplitude, and the strength of selectivity. These results argue against a purely feedforward explanation of recognition from partial information, and provide spatiotemporal constraints on theories of object recognition that involve recurrent processing.},
	keywords = {Adolescent, Adult, Brain Mapping, Child, Evoked Potentials, Visual, Female, Humans, Male, Pattern Recognition, Visual, Photic Stimulation, Reaction Time, Visual Cortex, Visual Fields, Visual Pathways, Young Adult},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2014.06.017},
	author = {Tang, Hanlin and Buia, Calin and Madhavan, Radhika and Crone, Nathan E and Madsen, Joseph R and Anderson, William S and Kreiman, Gabriel}
}
@article {509141,
	title = {Cell type-specific manipulation with GFP-dependent Cre recombinase.},
	journal = {Nat Neurosci},
	volume = {18},
	number = {9},
	year = {2015},
	month = {2015 Sep},
	pages = {1334-41},
	abstract = {There are many transgenic GFP reporter lines that allow the visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. We developed a method that exploits GFP for gene manipulation, Cre recombinase dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, which led to effective recombination selectively in GFP-labeled cells. Furthermore, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP(+) cells, we found that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins.},
	issn = {1546-1726},
	doi = {10.1038/nn.4081},
	author = {Tang, Jonathan C Y and Rudolph, Stephanie and Dhande, Onkar S and Abraira, Victoria E and Choi, Seungwon and Lapan, Sylvain W and Drew, Iain R and Drokhlyansky, Eugene and Huberman, Andrew D and Regehr, Wade G and Cepko, Constance L}
}
@article {1109881,
	title = {The Role of the Back Plate in Angle Anatomy with the Boston Type I Keratoprosthesis},
	journal = {Cornea},
	volume = {36},
	number = {9},
	year = {2017},
	month = {2017 Sep},
	pages = {1096-1101},
	abstract = {PURPOSE: To quantitatively evaluate the angle anatomy in eyes with the Boston type I keratoprosthesis (B-KPro) differing in the back plate (BP) material and size using anterior segment optical coherence tomography. METHODS: B-KPro eyes with poly(methyl methacrylate) (PMMA) (7.0 and 8.5 mm) and titanium (7.0, 8.5, and 9.5 mm) BPs were imaged with anterior segment optical coherence tomography. The angle opening distance at 500 μm from the scleral spur (AOD500), trabecular iris surface area at 500 μm from the scleral spur (TISA500), and trabecular iris angle at 500 μm from the scleral spur (TIA500) were measured. Among the visible quadrants, the average, the temporal, the widest, and the narrowest angle of each eye were included in the analysis. Average time between B-KPro implantation and imaging was 7.5 {\textpm} 1.4 years for a PMMA BP and 2.4 {\textpm} 2.3 years for a titanium BP (P \&lt; 0.0001). RESULTS: We analyzed 17 B-KPro eyes with PMMA BPs and 24 B-KPro eyes with titanium BPs. The average AOD500 (394.1 {\textpm} 226.9 vs. 454.5 {\textpm} 255.6 μm, P = 0.44), average TIA500 (26.2 {\textpm} 14.2 vs. 29.8 {\textpm} 13.9 degrees, P = 0.43), and average TISA500 (0.15 {\textpm} 0.08 vs. 0.17 {\textpm} 0.10 μm, P = 0.52) were not statistically different between eyes with PMMA and titanium BPs, nor were the temporal, the narrowest, and the widest angle measurements of each eye (all P \&gt; 0.05). Similarly, no significant differences were found between the angle measurements of B-KPro eyes with a titanium BP diameter of 8.5 or 9.5 mm (all P \&gt; 0.05). CONCLUSIONS: We successfully visualized the angle anatomy in 66.1\% of the imaged eyes, including all BPs studied. Neither the material nor the size of the B-KPro BP had a significant impact on the angle anatomy.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001248},
	author = {Taniguchi, Elise V and Paschalis, Eleftherios I and Crnej, Alja and Ren, Ai and Colby, Kathryn A and Chodosh, James and Pasquale, Louis R and Shen, Lucy Q and Dohlman, Claes H and Cruzat, Andrea}
}
@article {1109886,
	title = {N-Glycosylation affects the stability and barrier function of the MUC16 mucin},
	journal = {J Biol Chem},
	volume = {292},
	number = {26},
	year = {2017},
	month = {2017 Jun 30},
	pages = {11079-11090},
	abstract = {Transmembrane mucins are highly O-glycosylated glycoproteins that coat the apical glycocalyx on mucosal surfaces and represent the first line of cellular defense against infection and injury. Relatively low levels of N-glycans are found on transmembrane mucins, and their structure and function remain poorly characterized. We previously reported that carbohydrate-dependent interactions of transmembrane mucins with galectin-3 contribute to maintenance of the epithelial barrier at the ocular surface. Now, using MALDI-TOF mass spectrometry, we report that transmembrane mucin N-glycans in differentiated human corneal epithelial cells contain primarily complex-type structures with N-acetyllactosamine, a preferred galectin ligand. In N-glycosylation inhibition experiments, we find that treatment with tunicamycin and siRNA-mediated knockdown of the Golgi N-acetylglucosaminyltransferase I gene (MGAT1) induce partial loss of both total and cell-surface levels of the largest mucin, MUC16, and a concomitant reduction in glycocalyx barrier function. Moreover, we identified a distinct role for N-glycans in promoting MUC16{\textquoteright}s binding affinity toward galectin-3 and in causing retention of the lectin on the epithelial cell surface. Taken together, these studies define a role for N-linked oligosaccharides in supporting the stability and function of transmembrane mucins on mucosal surfaces.},
	issn = {1083-351X},
	doi = {10.1074/jbc.M116.770123},
	author = {Taniguchi, Takazumi and Woodward, Ashley M and Magnelli, Paula and McColgan, Nicole M and Lehoux, Sylvain and Jacobo, Sarah Melissa P and Mauris, J{\'e}r{\^o}me and Arg{\"u}eso, Pablo}
}
@article {688666,
	title = {Differentiation of murine models of "negative ERG" by single and repetitive light stimuli.},
	journal = {Doc Ophthalmol},
	volume = {132},
	number = {2},
	year = {2016},
	month = {2016 Apr},
	pages = {101-9},
	abstract = {PURPOSE: Marked attenuation of the single-flash electroretinographic (ERG) b-wave in the presence of a normal-amplitude or less-attenuated a-wave is commonly referred to as the "negative ERG." The purpose of this study was to investigate whether the disparate origins of the negative ERG in three murine models can be discriminated using flickering stimuli. METHODS: Three models were selected: (1) the Nyx (nob) mouse model of complete congenital stationary night blindness, (2) the oxygen-induced retinopathy (OIR) rat model of retinopathy of prematurity (ROP), and (3) the Rs1 knockout (KO) mouse model of X-linked juvenile retinoschisis. Directly after a dark-adapted, single-flash ERG luminance series, a flicker ERG frequency series (0.5-30\&nbsp;Hz) was performed at a fixed luminance of 0.5\&nbsp;log\&nbsp;cd\&nbsp;s/m(2). This series includes frequency ranges that are dominated by activity in (A) the rod pathways (below 5\&nbsp;Hz), (B) the cone ON-pathway (5-15\&nbsp;Hz), and (C) the cone OFF-pathway (above 15\&nbsp;Hz). RESULTS: All three models produced markedly attenuated single-flash ERG b-waves. In the Nyx (nob) mouse, which features postsynaptic deficits in the ON-pathways, the a-wave was normal and flicker responses were attenuated in ranges A and B, but not C. The ROP rat is characterized by inner-retinal ischemia which putatively affects both ON- and OFF-bipolar cell activity; flicker responses were reduced in all ranges (A-C). Notably, the choroid supplies the photoreceptors and is thought to be relatively intact in OIR, an idea supported by the nearly normal a-wave. Finally, in the Rs1 KO mouse, which has documented abnormality of the photoreceptor-bipolar synapse affecting both ON- and OFF-pathways, the flicker responses were attenuated in all ranges (A-C). The a-wave was also attenuated, likely as a consequence to schisms in the photoreceptor layer. CONCLUSION: Consideration of both single-flash and flickering ERG responses can discriminate the functional pathology of the negative ERG in these animal models of human disease.},
	issn = {1573-2622},
	doi = {10.1007/s10633-016-9534-1},
	author = {Tanimoto, Naoyuki and Akula, James D and Fulton, Anne B and Weber, Bernhard H F and Seeliger, Mathias W}
}
@article {1511491,
	title = {Bioengineered Acellular Dermal Matrix Spacer Grafts for Lower Eyelid Retraction Repair: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {127},
	number = {5},
	year = {2020},
	month = {2020 May},
	pages = {689-695},
	abstract = {PURPOSE: To review the literature on the efficacy and safety of bioengineered acellular dermal matrix (BADM) grafts for lower eyelid retraction repair. METHODS: A literature search was conducted in the PubMed database initially in January 2018 and updated in July 2019 to identify all studies in the English language literature on the use of BADM grafts in eyelid reconstruction. The searches yielded 193 citations, and 15 of the 34 articles selected for full review met\&nbsp;all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Two of the 15 studies included were rated level II and 13 were rated level III. RESULTS: The definition of success varied, but lower eyelid position improvement using lower lid margin-to-pupillary reflex distance was the most common outcome measure. Other end points were the amount of lagophthalmos, cosmesis, exposure, reoperation, or complications, as well as prosthesis retention in anophthalmic socket cases. The surgeon-reported success rate of these outcomes ranged from 75\% to 100\%. Minor complications included cyst formation, infection, chemosis, pyogenic granuloma, and corneal abrasion. No serious complications such as blindness, anaphylactic reaction, or terminal disease transmission occurred. Of the 526 implants included for assessment in these disparate studies, 27 cases (5\%) required reoperation. CONCLUSIONS: No level I evidence was available, and the existing level II and level III studies have variable primary end points, study design limitations, and only short-term follow-up data. The current literature suggests that BADM grafts represent an implantation option for lower eyelid retraction repair. Short-term results are favorable, and the materials used may fill an important gap in care for patients for whom no acceptable alternatives exist, but long-term safety and efficacy remain unknown.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.11.011},
	author = {Tao, Jeremiah P and Aakalu, Vinay K and Wladis, Edward J and Sobel, Rachel K and Freitag, Suzanne K and Foster, Jill A and Yen, Michael T}
}
@article {1598045,
	title = {Homeopathic Agents or Vitamins in Reducing Ecchymosis after Oculofacial Surgery: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {129},
	number = {2},
	year = {2022},
	month = {2022 02},
	pages = {220-226},
	abstract = {PURPOSE: To review the published literature to determine the efficacy and safety of homeopathic agents or vitamins in reducing ecchymosis after oculofacial surgery or laser surgery. METHODS: A literature search was conducted in the PubMed database initially in December 2019 and updated in March 2020 to identify all studies in the English language literature on the use of homeopathic agents or vitamins in oculofacial procedures, including laser surgery. The search yielded 124 citations, and 11 articles met\&nbsp;all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Eleven studies met inclusion criteria; 9 were rated level I, and 2 were rated level III. RESULTS: The agents studied in the articles identified included oral or topical Arnica montana (AM), oral Melilotus extract, topical vitamin K oxide, and topical AM combined with Rhododendron tomentosum. Metrics to describe ecchymosis varied. In 7 controlled studies, perioperative AM provided no or negligible benefit versus placebo. In 2 studies, vitamin K cream was equivalent to placebo. One study of oral Melilotus extract had less ecchymosis compared with controls in paranasal and eyelid ecchymosis at postoperative day (POD) 7, but not at PODs 1 and 4. A lone cohort study of combined topical AM and R.\&nbsp;tomentosum lacked objective metrics and adequate controls. No serious side effects from administration of homeopathic agents or vitamins were identified. CONCLUSIONS: The current literature does not support the use of AM, vitamin K oxide, R.\&nbsp;tomentosum, or Melilotus extract for reducing ecchymosis after oculofacial surgery or pulsed dye laser surgery.},
	keywords = {Academies and Institutes, Ecchymosis, Eyelid Diseases, Face, Humans, Materia Medica, Ophthalmologic Surgical Procedures, Ophthalmology, Paranasal Sinus Diseases, Plant Extracts, Technology Assessment, Biomedical, United States, Vitamin K},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.05.018},
	author = {Tao, Jeremiah P and Aakalu, Vinay K and Freitag, Suzanne K and Sobel, Rachel K and Foster, Jill A and Wladis, Edward J and McCulley, Timothy J and Yen, Michael T}
}
@article {1295879,
	title = {Delivery of Adeno-Associated Virus Vectors in Adult Mammalian Inner-Ear Cell Subtypes Without Auditory Dysfunction},
	journal = {Hum Gene Ther},
	volume = {29},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	pages = {492-506},
	abstract = {Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in humans with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to recover auditory functions effectively in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points, whereas in humans, the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damage to the inner ear. This study tested several AAV serotypes by canalostomy in adult mice. It is shown that most AAVs transduce the sensory inner hair cells efficiently, but are less efficient at transducing outer hair cells. A subset of AAVs also transduces non-sensory cochlear cell types. Neither the surgical procedure of canalostomy nor the AAV serotypes damage hair cells or impair normal hearing. The studies indicate that canalostomy can be a viable route for safe and efficient gene delivery, and they expand the repertoire of AAVs to target diverse cell types in the adult inner ear.},
	issn = {1557-7422},
	doi = {10.1089/hum.2017.120},
	author = {Tao, Yong and Huang, Mingqian and Shu, Yilai and Ruprecht, Adam and Wang, Hongyang and Tang, Yong and Vandenberghe, Luk H and Wang, Qiuju and Gao, Guangping and Kong, Wei-Jia and Chen, Zheng-Yi}
}
@article {1748496,
	title = {Thermal Pulsation in the Management of Meibomian Gland Dysfunction and Dry Eye: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {130},
	number = {12},
	year = {2023},
	month = {2023 Dec},
	pages = {1336-1341},
	abstract = {PURPOSE: To review the literature to determine the efficacy and safety of thermal pulsation technologies in improving signs or symptoms of meibomian gland dysfunction (MGD) and dry eye compared with no therapy or with conventional warm compress therapy or eyelid hygiene. METHODS: A literature search was conducted in the PubMed database in June 2022 and again in March 2023 to identify all studies in the English language on the use of thermal pulsation to treat MGD or dry eye. The search yielded 59 citations, and 11 articles met\&nbsp;all of the inclusion criteria. The panel methodologist then assigned a level of evidence rating for each study; 8 studies were rated level I evidence and 3 studies were rated level II evidence. RESULTS: All included studies evaluated a single 12-minute session using the LipiFlow automated thermal pulsation system (TearScience, Inc, or Johnson \&amp; Johnson). Improvements were detected in subjective and objective metrics of MGD or dry eye in patients within 1 to 12 months of thermal pulsation treatment compared with nontreatment. Most of the studies (9/11) reported greater efficacy with thermal pulsation than with standard warm compress therapy and eyelid hygiene. Four of these studies showed relevant industry conflicts of interest. Two of the 4 level I studies without direct industry participation concluded that thermal pulsation treatment was not significantly different from conventional hygiene or warm compress therapy control treatments (in symptoms in one of the studies and in objective findings in the second study). No serious adverse events were reported in any of the 11 studies. CONCLUSIONS: According to the current literature, a single thermal pulsation session may improve subjective or objective parameters of MGD and dry eye safely. However, industry support and participation were present in 4 of the 8 level I studies. The durability beyond several months and cost efficacy remain uncertain. Because the inclusion parameters of this assessment captured only the LipiFlow system, the conclusions are limited to that product. High-quality independent studies are needed to assess the long-term benefits of this intervention. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
	keywords = {Academies and Institutes, Benchmarking, Dry Eye Syndromes, Humans, Meibomian Gland Dysfunction, Ophthalmology},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.07.009},
	author = {Tao, Jeremiah P and Shen, Joanne F and Aakalu, Vinay K and Foster, Jill A and Freitag, Suzanne K and McCulley, Timothy J and Vagefi, M Reza and Kim, Stephen J and Wladis, Edward J}
}
@article {1806526,
	title = {Retinal artery to vein ratio is associated with cerebral microbleeds in individuals with type 1 diabetes},
	journal = {J Hypertens},
	year = {2024},
	month = {2024 Feb 28},
	abstract = {OBJECTIVES: A third of asymptomatic individuals with type 1 diabetes (T1D) show signs of cerebrovascular disease in brain MRI. These signs associate with advanced stages of diabetic retinal disease, but not in mild or moderate retinopathy. We aimed to evaluate a wider spectrum of retinal changes by exploring the relationship between quantitative measures of retinal vessel parameters (RVP) and cerebrovascular changes in T1D. METHODS: We included 146 neurologically asymptomatic individuals with T1D [51\% women, median age 40 (33.0-45.1) years] and 24 healthy, sex-matched and age-matched controls. All individuals underwent a clinical and biochemical work-up and brain MRI, which was evaluated for cerebral microbleeds (CMBs), white matter hyperintensities, and lacunar infarcts. RVPs, including central retinal arteriole (CRAE) and central retinal vein (CRVE) equivalents and the ratio of the two variables (arteriovenous ratio, AVR) were assessed quantitatively by a computer-assisted method (IVAN software, version 3.2.6) from fundus images. RESULTS: Among T1D participants, those with CMBs had a lower arteriovenous ratio (AVR) compared with those without CMBs (P = 0.023). AVR was inversely associated with the amount of CMBs (r = -0.063, P = 0.035). CMB prevalence was higher in those with AVR below the median (31\%) compared with above the median (16\%, P \&lt; 0.001), and this difference was significant also after individuals with only no-to-mild retinopathy were included (28 vs. 16\%, P = 0.005). A correlation between blood pressure and CRAE (r = -0.19, P = 0.025) appeared among those with T1D. CONCLUSION: Regardless of the severity of diabetic retinopathy, AVR is associated with the existence of CMBs in T1D.},
	issn = {1473-5598},
	doi = {10.1097/HJH.0000000000003690},
	author = {Tarkkonen, Aleksi and Fickweiler, Ward and Eriksson, Marika and Sun, Jennifer K and Thorn, Lena M and Summanen, Paula and Groop, Per-Henrik and Putaala, Jukka and Martola, Juha and Gordin, Daniel and FinnDiane Study Group}
}
@article {1498237,
	title = {Utility of Tear Osmolarity Measurement in Diagnosis of Dry Eye Disease},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Mar 26},
	pages = {5542},
	abstract = {The prevalence of dry eye disease is high worldwide and poses a great burden on patients{\textquoteright} daily lives. Accurate diagnosis of the disease is important, and it requires application of various methods. Hyperosmolarity is believed to be the disease marker and thus measuring it provides useful information. In this study we investigated utility of tear osmolarity measured with TearLab osmometer, along with other diagnostic tests (Ocular Surface Disease Index questionnaire, Tear film break-up time, Ocular Protection Index, Ocular Surface Staining, Schirmer I test, Meibomian gland functionality in 757 patients (1514 eyes) with dry eye disease and 29 healthy controls (58 eyes). Statistical differences between the patient group and the control group were observed for all the tests apart from tear osmolarity, regardless of cut-off value (\&gt;308 mOsm/L, \&gt;316 mOsm/L, and inter-eye difference \&gt;8 mOsm/L). Moreover, in the receiver operating characteristics curve analyses tear osmolarity measurement could not discriminate dry eye disease pathological scores. Therefore, our study suggests that tear osmolarity measured with TearLab osmometer cannot be used as a key indicator of DED.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-62583-x},
	author = {Tashbayev, Bezhod and Utheim, Tor Paaske and Utheim, {\O}ygunn Aass and R{\ae}der, Sten and Jensen, Janicke Liaaen and Yazdani, Mazyar and Lagali, Neil and Vitelli, Valeria and Dartt, Darlene A. and Chen, Xiangjun}
}
@article {1347446,
	title = {Thrombospondin-1 Is Necessary for the Development and Repair of Corneal Nerves},
	journal = {Int J Mol Sci},
	volume = {19},
	number = {10},
	year = {2018},
	month = {2018 Oct 16},
	abstract = {Thrombospondin-1-deficient (TSP-1) mice are used as an animal model of Sj{\"o}gren{\textquoteright}s Syndrome because they exhibit many of the symptoms associated with the autoimmune type of dry eye found in primary Sj{\"o}gren{\textquoteright}s Syndrome. This type of dry eye is linked to the inflammation of the lacrimal gland, conjunctiva, and cornea, and is thought to involve dysfunction of the complex neuronal reflex arc that mediates tear production in response to noxious stimuli on the ocular surface. This study characterizes the structural and functional changes to the corneal nerves that are the afferent arm of this arc in young and older TSP-1 and wild type (WT) mice. The structure and subtype of nerves were characterized by immunohistochemistry, in vivo confocal microscopy, and confocal microscopy. Cytokine expression analysis was determined by Q-PCR and the number of monocytes was measured by immunohistochemistry. We found that only the pro-inflammatory cytokine MIP-2 increased in young corneas of TSP-1 compared to WT mice, but tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) all increased in older TSP-1 mouse corneas. In contrast, CD11b+ pro-inflammatory monocytes did not increase even in older mouse corneas. Calcitonin gene-related peptide (CGRP)-, but not Substance P (SubP)-containing corneal nerves decreased in older, but not younger TSP-1 compared to WT mouse corneas. We conclude that CGRP-containing corneal sensory nerves exhibit distinct structural deficiencies as disease progresses in TSP-1 mice, suggesting that: (1) TSP-1 is needed for the development or repair of these nerves and (2) impaired afferent corneal nerve structure and hence function may contribute to ocular surface dysfunction that develops as TSP-1 mice age.},
	issn = {1422-0067},
	doi = {10.3390/ijms19103191},
	author = {Tatematsu, Yukako and Khan, Qalbi and Blanco, Tomas and Bair, Jeffrey A and Hodges, Robin R and Masli, Sharmila and Dartt, Darlene A.}
}
@article {603826,
	title = {The Role of Intraflagellar Transport in the Photoreceptor Sensory Cilium.},
	journal = {Adv Exp Med Biol},
	volume = {854},
	year = {2016},
	month = {2016},
	pages = {627-33},
	abstract = {The photoreceptor is a complex specialized cell in which a major component responsible for visual transduction is the photoreceptor sensory cilium (PSC). Building and maintenance of the PSC requires the transport of large proteins along microtubules that extend from the inner segments to the outer segments. A key process, termed intraflagellar transport (IFT), has been recognized as an essential phenomenon for photoreceptor development and maintenance, and exciting new studies have highlighted its importance in retinal and cilia related diseases. This review focuses on the important roles of IFT players, including motor proteins, IFT proteins, and photoreceptor-specific cargos in photoreceptor sensory cilium. In addition, specific IFT components that are involved in inherited human diseases are discussed.},
	issn = {0065-2598},
	doi = {10.1007/978-3-319-17121-0_83},
	author = {Taub, Daniel G and Liu, Qin}
}
@article {1309961,
	title = {Familial Exudative Vitreoretinopathy: Pathophysiology, Diagnosis, and Management},
	journal = {Asia Pac J Ophthalmol (Phila)},
	volume = {7},
	number = {3},
	year = {2018},
	month = {2018 May-Jun},
	pages = {176-182},
	abstract = {Familial exudative vitreoretinopathy (FEVR) is a heritable vitreoretinopathy characterized by anomalous retinal vascular development. The principal feature of the disease is an avascular peripheral retina. This in turn can cause further pathological changes including neovascularization, exudation, hemorrhage, and retinal detachment. The biological basis of the disease is thought to be from defects in the Wnt signaling pathway. Many gene mutations have been implicated, and these can be inherited in an autosomal dominant (most common), autosomal recessive, and X-linked recessive fashion. Examination with wide-field fluorescein angiography is essential and can identify the disease in its earlier stages, enabling timely treatment, in addition to helping identify asymptomatic family members. The current treatment paradigm involves laser photocoagulation of the avascular peripheral retina for neovascular sequelae and vitreoretinal surgery for progressive retinal detachment. Further studies are underway to better characterize this complex vitreoretinopathy.},
	keywords = {Diagnostic Techniques, Ophthalmological, Genetic Therapy, Humans, Retinal Diseases, Visual Acuity, Vitreoretinal Surgery},
	issn = {2162-0989},
	doi = {10.22608/APO.201855},
	author = {Tauqeer, Zujaja and Yonekawa, Yoshihiro}
}
@article {1295880,
	title = {Orbital Extranodal Marginal Zone Lymphoma Following Radiotherapy: A Report of 2 Cases},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2018},
	month = {2018 Jan 09},
	abstract = {PURPOSE: To present 2 patients in whom orbital radiation preceded the development of periorbital extranodal marginal zone lymphoma by more than a decade and to investigate the likelihood of this representing irradiation-induced malignancy. METHODS: Retrospective chart review and histopathologic study with immunohistochemistry of 2 cases. RESULTS: The first patient was a 58-year-old woman who developed an orbital mass within the vicinity of the lateral rectus muscle 17 years after external beam proton radiation therapy for an inferotemporal choroidal melanoma. The second patient was a 32-year-old woman who developed a mass in the right lacrimal gland 12 years after external beam photon radiation therapy for chronic inflammatory dacryoadenitis. Histopathologic and immunohistochemical studies confirmed orbital extranodal marginal zone lymphoma in both cases. Retrospective review of older histopathologic slides from the second patient revealed underlying immunoglobulin G4-related disease. DISCUSSION: The unusual sequence of events in these 2 cases raises the question of whether orbital radiation may in rare instances promote the development of orbital extranodal marginal zone lymphoma. The literature pertaining to irradiation-induced secondary malignancy in the orbit is reviewed. CONCLUSIONS: Clinicians should consider the possibility of a secondary malignancy when evaluating a patient with an orbital mass and a history of prior local radiation exposure.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001043},
	author = {Tauqeer, Zujaja and Jakobiec, Frederick A and Freitag, Suzanne K and Yoon, Michael K and Wolkow, Natalie}
}
@article {1748341,
	title = {Association of Dry Eye Symptoms and Signs in Patients with Dry Eye Disease},
	journal = {Ophthalmic Epidemiol},
	year = {2023},
	month = {2023 Aug 17},
	pages = {1-9},
	abstract = {PURPOSE: To determine the correlations among symptoms and signs of dry eye disease (DED) in the Dry Eye Assessment and Management (DREAM) study. METHODS: A total of 535 patients with moderate-to-severe DED were assessed for symptoms using the Ocular Surface Disease Index (OSDI) and four DED signs in both eyes (conjunctival lissamine green staining, corneal fluorescein staining, Schirmer{\textquoteright}s testing, and tear break-up time (TBUT)) following standardized protocols at baseline and follow-up visits (months 3, 6, and 12). Spearman correlation coefficients (rho) were calculated for correlations among symptoms and signs of DED at baseline and among changes in symptoms and signs from baseline at 12 months. The confidence intervals and p-values for correlation coefficients were calculated using a cluster bootstrapping to account for inter-eye correlation. RESULTS: At baseline, OSDI total score was not correlated with signs; however, OSDI subscale score of ocular symptoms was weakly correlated with corneal staining score (rho = 0.14, p = .002) and Schirmer test score (rho = 0.11, p = .01). There were statistically significant correlations among the four signs (p \&lt; .001), with absolute correlation coefficient ranging from 0.14 (conjunctival staining score vs. TBUT) to 0.33 (conjunctival staining score vs. cornea staining score). The correlations among changes in symptoms and signs were weaker, with the highest correlation between change in conjunctival staining and corneal staining (rho = 0.21, p \&lt; .001). CONCLUSIONS: Consistent with previous studies, among DREAM participants with moderate-to-severe DED at baseline, correlations of DED symptoms with signs were low and correlations among four objective signs were low to moderate. The correlations among changes in symptoms and signs were even weaker.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2023.2248629},
	author = {Tawfik, Andrew and Pistilli, Maxwell and Maguire, Maureen G and Chen, Yineng and Yu, Yinxi and Greiner, Jack V and Asbell, Penny A and Ying, Gui-Shuang and Dry Eye Assessment and Management (DREAM) Study Research Group}
}
@article {1538319,
	title = {Smart filtering of phase residues in noisy wrapped holograms},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Oct 12},
	pages = {16965},
	abstract = {Phase unwrapping is one of the major challenges in multiple branches of science that extract three-dimensional information of objects from wrapped signals. In several applications, it is important to extract the unwrapped information with minimal signal resolution degradation. However, most of the denoising techniques for unwrapping are designed to operate on the entire phase map to remove a limited number of phase residues, and therefore they significantly degrade critical information contained in the image. In this paper, we present a novel, smart, and automatic filtering technique for locally minimizing the number of phase residues in noisy wrapped holograms, based on the phasor average filtering (PAF) of patches around each residue point. Both patch sizes and PAF filters are increased in an iterative algorithm to minimize the number of residues and locally restrict the artifacts caused by filtering to the pixels around the residue pixels. Then, the improved wrapped phase can be unwrapped using a simple phase unwrapping technique. The feasibility of our method is confirmed by filtering, unwrapping, and enhancing the quality of a noisy hologram of neurons; the intensity distribution of the spatial frequencies demonstrates a 40-fold improvement, with respect to previous techniques, in preserving the higher frequencies.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-74131-8},
	author = {Tayebi, Behnam and Sharif, Farnaz and Han, Jae-Ho}
}
@article {1559533,
	title = {Patrolling Monocytes Are Recruited and Activated by Diabetes to Protect Retinal Microvessels},
	journal = {Diabetes},
	volume = {69},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {2709-2719},
	abstract = {In diabetes there is a long latency between the onset of hyperglycemia and the appearance of structural microangiopathy. Because Ly6C patrolling monocytes (PMo) behave as housekeepers of the vasculature, we tested whether PMo protect microvessels against diabetes. We found that in wild-type mice, diabetes reduced PMo in the general circulation but increased by fourfold the absolute number of PMo adherent to retinal vessels (leukostasis). Conversely, in diabetic NR4A1 mice, a model of absence of PMo, there was no increase in leukostasis, and at 6 months of diabetes, the number of retinal acellular capillaries almost doubled compared with diabetic wild-type mice. Circulating PMo showed gene expression changes indicative of enhanced migratory, vasculoprotective, and housekeeping activities, as well as profound suppression of genes related to inflammation and apoptosis. Promigratory CXCR4 was no longer upregulated at longer duration when retinal acellular capillaries begin to increase. Thus, after a short diabetes duration, PMo are the cells preferentially recruited to the retinal vessels and protect vessels from diabetic damage. These observations support the need for reinterpretation of the functional meaning of leukostasis in diabetes and document within the natural history of diabetic retinopathy processes of protection and repair that can provide novel paradigms for prevention.},
	issn = {1939-327X},
	doi = {10.2337/db19-1043},
	author = {Tecilazich, Francesco and Phan, Toan A and Simeoni, Fabio and Scotti, Giulia Maria and Dagher, Zeina and Lorenzi, Mara}
}
@article {692326,
	title = {Defective Myogenic Response of Retinal Vessels Is Associated With Accelerated Onset of Retinopathy in Type 1 Diabetic Individuals.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {4},
	year = {2016},
	month = {2016 Apr 1},
	pages = {1523-9},
	abstract = {PURPOSE: We seek to identify pathogenic mechanisms for diabetic retinopathy that can become therapeutic targets beyond hyperglycemia and hypertension. We investigated if a defective myogenic response of retinal arteries to increased perfusion pressure, which exposes capillaries to increased pressure and flow, is associated with the onset of clinical retinopathy. METHODS: We examined prospectively the incidence of retinopathy in type 1 diabetic individuals tested 4 years earlier for the retinal arterial myogenic response, and in a cross-sectional study the prevalence of defective myogenic response in type 1 patients who had diabetic retinopathy. Among these, we contrasted early-onset (after 15 {\textpm} 2 years of diabetes, E-DR; n = 5) to late-onset (after 26 {\textpm} 3 years of diabetes, L-DR; n = 7) retinopathy. We measured the myogenic response using a laser Doppler blood flowmeter after a change in posture from sitting to reclining, which increases retinal perfusion pressure. RESULTS: Five of seven participants who 4 years prior had a defective myogenic response had now developed clinical retinopathy; as compared with only one of six participants who 4 years prior had a normal response (P = 0.10). In the cross-sectional study, all participants had normal retinal hemodynamics at steady state. In response to the postural change, only the E-DR group showed defective myogenic response (P = 0.005 versus controls, P = 0.02 versus L-DR) and abnormally high retinal blood flow (P = 0.016 versus controls). CONCLUSIONS: In type 1 diabetic patients, a defective myogenic response of retinal arteries to pressure is not required for the development of clinical retinopathy, but is prominently associated with an accelerated onset of retinopathy.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18356},
	author = {Tecilazich, Francesco and Feke, Gilbert T and Mazzantini, Sara and Sobrin, Lucia and Lorenzi, Mara}
}
@article {1817276,
	title = {Factors Associated With Incidental Retinal Emboli in the U.S. Adult Population},
	journal = {Am J Ophthalmol},
	volume = {257},
	year = {2024},
	month = {2024 Jan},
	pages = {34-37},
	abstract = {PURPOSE: We sought to estimate the prevalence of incidental retinal emboli and identify associated factors using a nationally representative sample of the U.S.

DESIGN: Cross-sectional study.

METHODS: We included adult (age >=40 years) participants of the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Incidental retinal emboli were identified through retinal fundus photography. Multivariable logistic regression was used to determine the association between the presence of retinal emboli and sociodemographic, lifestyle, and clinical factors (age, sex, race/ethnicity, education, income, smoking, alcohol use, body mass index [BMI], hypertension, diabetes, hypercholesterolemia, and history of cardiovascular disease).

RESULTS: This study included 5,764 adults (53\% female). Incidental retinal emboli were identified in 0.7\% (39/5764) of individuals. The survey-weighted prevalence of retinal emboli increased with age, from 0.1\% in participants 40-49 years of age to 1.4\% in participants>=70 years of age. The prevalence did not differ by sex or race/ethnicity. Factors associated with retinal emboli after adjusting for age and sex included underweight BMI (odds ratio [OR] 7.24 [95\% confidence interval {CI} 1.06-49.3]), current smoking (OR 6.16 [95\% CI 1.49-25.5]), low household income (OR 4.41 [95\% CI 1.3-15.0]), and hypertension (OR 2.67 [95\% CI 1.31-5.44]).

CONCLUSIONS: In a cohort representative of the U.S. adult population, the prevalence of incidental retinal emboli increased with age but did not differ by sex, race, or ethnicity. Further investigation into the potential association of socioeconomic and nutritional status with retinal emboli may enable opportunities to identify individuals with underlying cardiovascular risk.},
	keywords = {Adult, Cross-Sectional Studies, Embolism, Female, Humans, Hypertension, Infant, Male, Middle Aged, Nutrition Surveys, Prevalence, Retinal Diseases, Risk Factors},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.08.008},
	author = {Teebagy, Sean and Jastrzembski, Benjamin G and Oke, Isdin}
}
@article {1709736,
	title = {The Association of Vision Concerns With the Physical and Mental Well-being of Adolescents in the United States},
	journal = {Am J Ophthalmol},
	volume = {256},
	year = {2023},
	month = {2023 Dec},
	pages = {35-38},
	abstract = {PURPOSE: To describe the prevalence of vision concerns among US adolescents and the association of time spent worrying about eyesight with physical and mental health. DESIGN: Cross-sectional study. METHODS: This study included adolescent children (age 12 to <=18 years) particpating in the 2005-2008 National Health and Nutrition Examination Survey with completed visual function questionnaires and eye examinations. Vision concerns were identified by a survey question of time spent worrying about eyesight and response was treated as a dichotomous variable. Recent poor physical and mental health was defined as at least 1 day of poor health within the last month. Odds ratios (ORs) derived from survey-weighted multivariable logistic regression models were used to identify factors associated with vision concerns in the adolescent population, adjusting for participant demographics and refractive correction. RESULTS: The survey participants included 3100 adolescents (mean [SD] age, 15.5 [2.0] years; 49\% [n\&nbsp;=\&nbsp;1545] female). Vision concerns were expressed by 24\% (n=865) of adolescents. Vision concerns were more prevalent among female (29\% vs 19\%, P \&lt; .001), low-income (30\% vs 23\%, P \&lt; .001), and uninsured (31\% vs 22\%, P\&nbsp;=\&nbsp;.006) adolescents. Participants worried about their eyesight were more likely to have undercorrected refractive error (OR 2.07, 95\% CI 1.43-2.98). Poor recent mental health (OR 1.30, 95\% CI 1.01-1.67), but not physical health (OR 1.00, 95\% CI 0.69-1.45), was associated with adolescent vision concerns. CONCLUSIONS: Female, low-income, and uninsured adolescents living in the United States are more likely to report worrying about their vision and often have uncorrected or undercorrected refractive errors.},
	keywords = {Adolescent, Child, Cross-Sectional Studies, Female, Humans, Mental Health, Nutrition Surveys, Prevalence, Refractive Errors, United States, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.05.018},
	author = {Teebagy, Sean and Jastrzembski, Benjamin G and Oke, Isdin}
}
@article {1137911,
	title = {Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome},
	journal = {Am J Med Genet A},
	volume = {173},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {2763-2771},
	abstract = {Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G\&gt;C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G\&gt;C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.38375},
	author = {Telegrafi, Aida and Webb, Bryn D and Robbins, Sarah M and Speck-Martins, Carlos E and FitzPatrick, David and Fleming, Leah and Redett, Richard and Dufke, Andreas and Houge, Gunnar and van Harssel, Jeske J T and Verloes, Alain and Robles, Angela and Manoli, Irini and Engle, Elizabeth C and Moebius Syndrome Research Consortium and Jabs, Ethylin W and Valle, David and Carey, John and Hoover-Fong, Julie E and Sobreira, Nara L M}
}
@article {1360123,
	title = {Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sj{\"o}gren Syndrome},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {13},
	year = {2018},
	month = {2018 Nov 01},
	pages = {5599-5614},
	abstract = {Purpose: Sj{\"o}gren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods: Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results: Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sj{\"o}gren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions: These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sj{\"o}gren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-25772},
	author = {Tellefsen, Sara and Morthen, Mathias Kaurstad and Richards, Stephen M and Lieberman, Scott M and Rahimi Darabad, Raheleh and Kam, Wendy R and Sullivan, David A}
}
@article {1549024,
	title = {Sex and age differences in symptoms and signs of dry eye disease in a Norwegian cohort of patients},
	journal = {Ocul Surf},
	year = {2020},
	month = {2020 Nov 24},
	abstract = {PURPOSE: To investigate sex and age differences in symptoms and signs in a Norwegian clinic-based cohort of patients with dry eye disease (DED). METHODS: Visitors at the Norwegian Dry Eye Clinic were examined using Ocular Surface Disease Index (OSDI) questionnaire score, tear osmolarity, tear break-up time (TFBUT), ocular surface staining, corneal sensitivity, Schirmer I test, and meibum expressibility (ME) and quality (MQ). A diagnosis of DED was made by an ophthalmologist based on symptoms and signs, and only DED patients were enrolled in the study: 1823 patients (338 males; mean age 51.2 {\textpm} 16.2 years; 1485 females; mean age 52.5 {\textpm} 16.0 years). The patients were divided into age subgroups: 20-39 years, 40-59 years and >=60 years. Sex differences in the aforementioned tests were analyzed. Values were reported as mean {\textpm} standard deviation (SD), and intergroup comparisons were performed using Mann-Whitney U test. Multiple regression was used to analyze sex and age influences on symptoms and signs. RESULTS: When patients of all ages were analyzed, females had increased osmolarity, shorter TFBUT, reduced MQ and ME and higher corneal sensitivity. OSDI, Schirmer I test, ocular surface staining and corneal staining were not significantly different between the sexes. Only with TFBUT and ME were the sex difference present in all age subgroups. Multiple regression showed that all parameters were influenced by either sex or age, but only TFBUT and ME were influenced by both sex and age. (all p \&lt; 0.05). CONCLUSIONS: Sex and age differences in dry eye were most consistent in TFBUT and ME, that indicate differences in meibomian gland functionality. Sex and age subgroup stratification is important in future studies investigating DED in other populations.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.11.009},
	author = {Tellefsen, Sara and Badian, Reza A and Utheim, Tor P and Utheim, {\O}ygunn A and Stojanovic, Aleksandar and Tashbayev, Behzod and Raeder, Sten and Dartt, Darlene A. and Chen, Xiangjun}
}
@article {1470982,
	title = {Etv1 Controls the Establishment of Non-overlapping Motor Innervation of Neighboring Facial Muscles during Development},
	journal = {Cell Rep},
	volume = {29},
	number = {2},
	year = {2019},
	month = {2019 Oct 08},
	pages = {437-452.e4},
	abstract = {The somatotopic motor-neuron projections onto their cognate target muscles are essential for coordinated movement, but how that occurs for facial motor circuits, which have critical roles in respiratory and interactive behaviors, is poorly understood. We report extensive molecular heterogeneity in developing facial motor neurons in the mouse and identify markers of subnuclei and the motor pools innervating specific facial muscles. Facial subnuclei differentiate during migration to the ventral hindbrain, where neurons with progressively later birth dates-and evolutionarily more recent functions-settle in more-lateral positions. One subpopulation marker, ETV1, determines both positional and target muscle identity for neurons of the dorsolateral (DL) subnucleus. In Etv1 mutants, many markers of DL differentiation are lost, and individual motor pools project indifferently to their own and neighboring muscle targets. The resulting aberrant activation patterns are reminiscent of the facial synkinesis observed in humans after facial nerve injury.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2019.08.078},
	author = {Tenney, Alan P and Livet, Jean and Belton, Timothy and Prochazkova, Michaela and Pearson, Erica M and Whitman, Mary C and Kulkarni, Ashok B and Engle, Elizabeth C and Henderson, Christopher E}
}
@article {1709666,
	title = {Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis},
	journal = {Nat Genet},
	volume = {55},
	number = {7},
	year = {2023},
	month = {2023 Jul},
	pages = {1149-1163},
	abstract = {Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.},
	keywords = {Animals, Facial Paralysis, GATA2 Transcription Factor, Mice, Motor Neurons, neurogenesis, Neurons, Efferent},
	issn = {1546-1718},
	doi = {10.1038/s41588-023-01424-9},
	author = {Tenney, Alan P and Di Gioia, Silvio Alessandro and Webb, Bryn D and Chan, Wai-Man and de Boer, Elke and Garnai, Sarah J and Barry, Brenda J and Ray, Tammy and Kosicki, Michael and Robson, Caroline D and Zhang, Zhongyang and Collins, Thomas E and Gelber, Alon and Pratt, Brandon M and Fujiwara, Yuko and Varshney, Arushi and Lek, Monkol and Warburton, Peter E and Van Ryzin, Carol and Lehky, Tanya J and Zalewski, Christopher and King, Kelly A and Brewer, Carmen C and Thurm, Audrey and Snow, Joseph and Facio, Flavia M and Narisu, Narisu and Bonnycastle, Lori L and Swift, Amy and Chines, Peter S and Bell, Jessica L and Suresh Mohan and Whitman, Mary C and Staffieri, Sandra E and Elder, James E and Demer, Joseph L and Torres, Alcy and Rachid, Elza and Al-Haddad, Christiane and Boustany, Rose-Mary and Mackey, David A and Brady, Angela F and Fenollar-Cort{\'e}s, Mar{\'\i}a and Fradin, Melanie and Kleefstra, Tjitske and Padberg, George W and Raskin, Salmo and Sato, Mario Teruo and Orkin, Stuart H and Parker, Stephen C J and Hadlock, Tessa A and Vissers, Lisenka E L M and van Bokhoven, Hans and Jabs, Ethylin Wang and Collins, Francis S and Pennacchio, Len A and Manoli, Irini and Engle, Elizabeth C}
}
@article {416856,
	title = {Mullers Muscle Conjunctival Resection for Treatment of Contact Lens-Associated Ptosis.},
	journal = {Ophthal Plast Reconstr Surg},
	volume = {32},
	number = {4},
	year = {2016},
	month = {2016 Jul-Aug},
	pages = {257-60},
	abstract = {PURPOSE: The aim of this study was to look at the surgical outcomes of posterior approach Mullers muscle conjunctival resection surgery for contact lens-related ptosis. METHODS: This was a retrospective, comparative interventional case series. All patients and controls underwent phenylephrine 10\% testing and had a positive response prior to surgical intervention. RESULTS: Thirty-one eyelids with ptosis were identified in 20 contact lens wearing patients, which were matched with 27 eyelids in 15 controls. The contact lens wearing patients wore contact lenses for a mean of 20.6 {\textpm} 12.1 years. More than half (60\%) wore soft contact lenses, as opposed to rigid gas-permeable contact lenses. Preoperative margin-to-reflex distance-1 was lower in patients who wore rigid contact lenses (0.8 {\textpm} 0.7 mm) as compared with patients with soft contact lenses (1.7 {\textpm} 1.1 mm) (p = 0.01). Surgical success, as defined by margin-to-reflex distance-1 >=3 mm or symmetry of upper eyelid height (within 1 mm), was achieved in 93.5\% in the contact lens group and 92.6\% of controls. Postoperative margin-to-reflex distance-1 was significantly higher in the contact lens wearers (3.9 {\textpm} 1.3 mm) compared with the controls (3.2 {\textpm} 1.1 mm; p = 0.01). There was a significant correlation between the amount of tissue resected intraoperatively and the improvement in margin-to-reflex distance-1 (Pearsons correlation coefficient, r =0.36; p = 0.006). There were no surgical complications of any patients in the study. CONCLUSION: Mullers muscle conjunctival resection surgery is an effective surgical correction for contact lens-associated ptosis. Patients can achieve excellent results with minimal risk of residual ptosis or asymmetry.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000479},
	author = {Teo, Livia and Lagler, Christine P and Mannor, Geva and Glass, Lora D and Freitag, Suzanne K}
}
@article {655071,
	title = {Use of a retinal sponge for silicone tube fixation after bicanalicular lacrimal intubation or dacryocystorhinostomy.},
	journal = {Orbit},
	volume = {35},
	number = {2},
	year = {2016},
	month = {2016 Apr},
	pages = {97},
	issn = {1744-5108},
	doi = {10.3109/01676830.2015.1099696},
	author = {Teo, Livia and Bleier, Benjamin and Lim, Laurence and Freitag, Suzanne}
}
@article {1619411,
	title = {Refractive Error of Students (15- to 18-year-olds) in Northwest Mexico},
	journal = {Optom Vis Sci},
	volume = {98},
	number = {10},
	year = {2021},
	month = {2021 Oct 01},
	pages = {1127-1131},
	abstract = {SIGNIFICANCE: We assessed the prevalence of refractive error in a sample of children of Northern Mexico using the Refractive Error Study in Children protocol of the World Health Organization, which allows for the comparison with other global studies. PURPOSE: Uncorrected refractive error is the main cause of visual impairment in children. The purpose of this study was to assess the refractive error and visual dysfunctions of students (15 to 18 years old) in the upper-middle school system of Sinaloa, Mexico. METHODS: A total of 3468 students in Sinaloa{\textquoteright}s high school system participated in the study from 2017 to 2019. Optometrists and student clinicians from the Optometry Program of the Autonomous University of Sinaloa conducted the testing. Tests included visual acuities and static retinoscopy. We did not use a cycloplegic agent. RESULTS: The results showed a high prevalence of uncorrected refractive errors. Myopia, defined as a refractive error <=-0.50 D, had a prevalence of 36.11\% (95\% confidence interval, 33.47 to 38.83\%); hyperopia, defined as a refractive error >=+2.00 D, had a prevalence of 1.49\% (95\% confidence interval, 0.09 to 2.33\%); and astigmatism, defined as a refractive error with a cylinder >=0.75 D, had a prevalence of 29.17\% (95\% confidence interval, 26.60 to 31.76\%). We found a significant effect of sex on visual acuity. CONCLUSIONS: Our results are consistent with a high prevalence of myopia reported in adolescents worldwide and in Mexico{\textquoteright}s northern regions. The results suggest that students attending high school and entering universities should be required to have an optometric eye examination. Additional studies are needed to investigate the prevalence of refractive errors in children in Mexico.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001779},
	author = {Teran, Emiliano and Ram{\'\i}rez-Jaime, Rosal{\'\i}a and Mart{\'\i}nez-Gayt{\'a}n, Carlos and Romo-Garc{\'\i}a, Efrain and Costela, Francisco M}
}
@article {1498265,
	title = {Evaluation of Two Strategies for Alleviating the Impact on the Circadian Cycle of Smartphone Screens},
	journal = {Optom Vis Sci},
	volume = {97},
	number = {3},
	year = {2020},
	month = {2020 Mar},
	pages = {207-217},
	abstract = {SIGNIFICANCE: Electronic display devices used before bed may negatively affect sleep quality through the effects of short-wavelength (blue) light on melatonin production and the circadian cycle. We quantified the efficacy of night-mode functions and blue-light-reducing lenses in ameliorating this problem. PURPOSE: The purpose of this study was to compare the radiation produced by smartphones that reaches the eye when using night-mode functions or blue-light-reducing spectacle lenses. METHODS: Radiant flux of 64 smartphones was measured with an integrating sphere. The retinal illuminance was calculated from the radiant flux of the smartphones. For the night-mode functions, the spectra produced by the smartphones were measured. The transmittance of four blue-light-reducing spectacle lenses, which filter light with either antireflective coatings or tints, was measured using a spectrometer. To determine the impact of blue-light-reducing spectacles, the radiant flux of the smartphone was weighted by the transmission spectrum of these glasses. Visual and nonvisual (circadian) parameters were calculated to compute the melatonin suppression values (MSVs) through a logistic fitting of previously published data. The MSV was used as the figure of merit to evaluate the performance of blue-light spectacles and smartphone night-mode functions. RESULTS: Night-mode functions in smartphones reduced MSVs by up to 93\%. The warmest mode produced the least suppression. Blue-light-reducing spectacles reduced melatonin suppression by 33\%, the coated lenses being more efficient than tinted lenses. CONCLUSIONS: All smartphones in this study emit radiant power in the short-wavelength region of the visible spectrum. Such smartphones may impair the regulation of circadian cycles at nighttime. The activation of night-mode functions was more efficient than the commercially available blue-light-reducing spectacle lenses in reducing the amount of short-wavelength light (up to 2.25 times). These results can be extrapolated to most electronic devices because they share the same type of white radiant sources with smartphones.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000001485},
	author = {Teran, Emiliano and Yee-Rendon, Cristo-Manuel and Ortega-Salazar, Jesus and De Gracia, Pablo and Garcia-Romo, Efrain and Woods, Russell L}
}
@article {1474190,
	title = {Tubercular Uveitis: Nuggets from Collaborative Ocular Tuberculosis Study (COTS)-1},
	journal = {Ocul Immunol Inflamm},
	year = {2019},
	month = {2019 Nov 25},
	pages = {1-9},
	abstract = {Tuberculosis (TB) is a major infection that can affect the eye as first and sole presentation without features of systemic disease. Controversy exists regarding diagnosis and management of tubercular uveitis (TBU), further compounded by regional variations in disease expression. Collaborative Ocular Tuberculosis Study (COTS)-1 aims to address knowledge deficits through collaboration amongst uveitis specialists across the globe by sharing the data of patients with TBU presented at participating centers from January 2004 to December 2014. Data collection was facilitated by a novel method of real-time encrypted web-based data entry allowing regular updates as new data and recommendations become available. Information on clinical features, investigation findings, management, and treatment outcomes were reviewed to get an idea about real world scenario. The current review aims to focus on methodology and briefing of published reports from COTS group in COTS-1 study to highlight key messages from this large data.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2019.1646774},
	author = {Testi, Ilaria and Agrawal, Rupesh and Mahajan, Sarakshi and Agarwal, Aniruddha and Gunasekeran, Dinesh Visva and Raje, Dhananjay and Aggarwal, Kanika and Murthy, Somasheila I and Westcott, Mark and Chee, Soon Phaik and McCluskey, Peter and Ho, Su Ling and Teoh, Stephen and Cimino, Luca and Biswas, Jyotirmay and Narain, Shishir and Agarwal, Manisha and Mahendradas, Padmamalini and Khairallah, Moncef and Jones, Nicholas and Tugal-Tutkun, Ilknur and Babu, Kalpana and Basu, Soumayava and Carre{\~n}o, Ester and Lee, Richard and Al-Dhibi, Hassan and Bodaghi, Bahram and Invernizzi, Alessandro and Goldstein, Debra A and Herbort, Carl P and Barisani-Asenbauer, Talin and Gonz{\'a}lez-L{\'o}pez, Julio J and Androudi, Sofia and Bansal, Reema and Moharana, Bruttendu and Esposti, Simona Degli and Tasiopoulou, Anastasia and Nadarajah, Sengal and Agarwal, Mamta and Abraham, Sharanya and Vala, Ruchi and Singh, Ramandeep and Sharma, Aman and Sharma, Kusum and Zierhut, Manfred and Rousselot, Andres and Grant, Robert and Kon, Onn Min and Cunningham, Emmett T and Kempen, John and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali}
}
@article {1528428,
	title = {The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Descriptive Review of Tubercular Uveitis in Paediatric Population},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Aug 17},
	pages = {1-7},
	abstract = {PURPOSE: To examine disease profile of tubercular uveitis (TBU) in Paediatric population. METHODS: Among 945 patients of the retrospective multinational study by the Collaborative Ocular Tuberculosis Study (COTS)-1, 29 Paediatric patients diagnosed with TBU were analyzed. RESULTS: Mean age of disease presentation was 12.8 (range 4-18\&nbsp;years), with predominance of males (n\&nbsp;=\&nbsp;14/20; 70.0\%) and Asian ethnicity (n\&nbsp;=\&nbsp;25/29; 86.2\%). Posterior uveitis (n\&nbsp;=\&nbsp;14/28; 50\%) was the most frequent uveitis phenotype, with choroidal involvement occurring in 64.7\% (n\&nbsp;=\&nbsp;11/17). Incidence of optic disc edema and macular edema was higher in children (n\&nbsp;=\&nbsp;8/18; 44.4\% and n =\&nbsp;5/18; 27.8\%, respectively) than in adults (n\&nbsp;=\&nbsp;160/942; 16.9\% and n =\&nbsp;135/942; 14.3\%, respectively). Comparison of optic disc edema between subgroups showed a significant difference (). All patients received oral corticosteroids, most of them with antitubercular therapy. Treatment failure developed in 4.8\% (n\&nbsp;=\&nbsp;1/21). CONCLUSIONS: Children have a more severe inflammatory response to the disease, and an intensive anti-inflammatory therapeutic regimen is required to achieve a positive treatment outcome.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1781197},
	author = {Testi, Ilaria and Agrawal, Rupesh and Mahajan, Sarakshi and Agarwal, Aniruddha and Gunasekeran, Dinesh Visva and Raje, Dhananjay and Aggarwal, Kanika and Murthy, Somasheila I and Westcott, Mark and Chee, Soon-Phaik and McCluskey, Peter and Ho, Su Ling and Teoh, Stephen and Cimino, Luca and Biswas, Jyotirmay and Narain, Shishir and Agarwal, Manisha and Mahendradas, Padmamalini and Khairallah, Moncef and Jones, Nicholas and Tugal-Tutkun, Ilknur and Babu, Kalpana and Basu, Soumayava and Carre{\~n}o, Ester and Lee, Richard and Al-Dhibi, Hassan and Bodaghi, Bahram and Invernizzi, Alessandro and Goldstein, Debra A and Herbort, Carl P and Barisani-Asenbauer, Talin and Gonz{\'a}lez-L{\'o}pez, Julio J and Androudi, Sofia and Bansal, Reema and Moharana, Bruttendu and Esposti, Simona Degli and Tasiopoulou, Anastasia and Nadarajah, Sengal and Agarwal, Mamta and Abraham, Sharanaya and Vala, Ruchi and Singh, Ramandeep and Sharma, Aman and Sharma, Kusum and Zierhut, Manfred and Kon, Onn Min and Cunningham, Emmett T and Kempen, John H and Nguyen, Quan Dong and Pavesio, Carlos and Gupta, Vishali}
}
@article {1598076,
	title = {Efficacy of a Single Administration of 5\% Povidone-Iodine in the Treatment of Adenoviral Conjunctivitis},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 Jun 05},
	abstract = {PURPOSE: To evaluate the safety and efficacy of a single, in-office administration of 5\% povidone-iodine (PVP-I) compared to artificial tears (AT) for adenoviral conjunctivitis (Ad-Cs). DESIGN: Double-masked pilot randomized trial METHODS: Patients presenting with presumed adenoviral conjunctivitis were screened at 9 U.S. clinics. INCLUSION CRITERIA: >= 18 years of age, symptoms <= 4 days and a positive AdenoPlus{\textregistered} test. EXCLUSION CRITERIA: thyroid disease, iodine allergy, recent ocular surgery, and ocular findings inconsistent with early-stage Ad-Cs. Randomization was to a single administration of 5\% PVP-I or AT in one eye and examinations on days 1-2, 4, 7, 14 and 21 with conjunctival swabs taken each visit for quantitative polymerase chain reaction. Primary outcome was percent reduction from peak viral load. Secondary outcomes were improvement in clinical signs and symptoms. RESULTS: Of 56 patients randomized, 28 had detectable viral titers at baseline. Day 4 post-treatment, viral titers in the 5\% PVP-I and AT groups were 2.5\% {\textpm} 2.7\% and 14.4\% {\textpm} 10.5\% of peak respectively (p=0.020). Severity of participant-reported tearing, lid swelling and redness as well as clinician-graded mucoid discharge, bulbar redness and bulbar edema were lower in the 5\% PVP-I group than AT group on Day 4 (p\&lt; 0.05). After Day 4, viral titers, severity of signs and symptoms decreased markedly in both groups and no differences between groups were detected. CONCLUSIONS: Pilot data suggest a single, in-office administration of 5\% PVP-I could reduce viral load and hasten improvement of clinical signs and symptoms in patients with Ad-Cs.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.05.018},
	author = {Than, Tammy and Morettin, Christina E and Harthan, Jennifer S and Hartwick, Andrew T E and Huecker, Julia B and Johnson, Spencer D and Migneco, Mary K and Shorter, Ellen and Whiteside, Meredith and Margolis, Mathew S and Olson, Christian K and Alferez, Christopher S and van Zyl, Tav{\'e} and Rodic-Polic, Bojana and Storch, Gregory A and Gordon, Mae O}
}
@article {1629475,
	title = {Erratum to Efficacy of a Single Administration of 5\% Povidone-Iodine in the Treatment of Adenoviral Conjunctivitis. Am J Ophthalmol 2021;231:28-38},
	journal = {Am J Ophthalmol},
	year = {2022},
	month = {2022 Jan 18},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.12.001},
	author = {Than, Tammy and Morettin, Christina E and Harthan, Jennifer S and Hartwick, Andrew T E and Huecker, Julia B and Johnson, Spencer D and Migneco, Mary K and Shorter, Ellen and Whiteside, Meredith and Margolis, Mathew S and Olson, Christian K and Alferez, Christopher S and van Zyl, Tav{\'e} and Rodic-Polic, Bojana and Storch, Gregory A and Gordon, Mae O}
}
@article {280841,
	title = {A 13-year-old boy with asthma, itchy eyes, and decreased vision.},
	journal = {J Pediatr},
	volume = {165},
	number = {6},
	year = {2014},
	month = {2014 Dec},
	pages = {1267},
	issn = {1097-6833},
	doi = {10.1016/j.jpeds.2014.07.044},
	author = {Thanos, Aristomenis and Mantagos, Iason S}
}
@article {560156,
	title = {Severe Vision Loss With Optic Disc Neovascularization After Hemiretinal Vascular Obstruction Associated With Optic Disc Melanocytoma.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {10},
	year = {2015},
	month = {2015 Oct 8},
	pages = {e151502},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.1502},
	author = {Thanos, Aristomenis and Gilbert, Aubrey L and Gragoudas, Evangelos S}
}
@article {1351201,
	title = {Ectopic (choristomatous) orbital respiratory cyst: histopathology and immunohistochemistry},
	journal = {Surv Ophthalmol},
	volume = {59},
	number = {3},
	year = {2014},
	month = {2014 May-Jun},
	pages = {328-33},
	abstract = {A 24-year-old woman underwent excision of a slowly growing mass located in the right superomedial orbit that had histopathologic and immunohistochemical findings consistent with a choristomatous respiratory cyst. This rare condition may either arise primarily from embryologic respiratory epithelium rests in the orbit or develop secondarily as the result of trauma or chronic sinus disease complicated by mucocele formation.},
	keywords = {Biomarkers, Choristoma, Female, Humans, Immunoenzyme Techniques, Keratin-17, Keratin-18, Mucocele, Orbital Diseases, Respiratory Mucosa, Tomography, X-Ray Computed, Young Adult},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2013.07.001},
	author = {Thanos, Aristomenis and Jakobiec, Frederick A and Mendoza, Pia R and Hatton, Mark P}
}
@article {742316,
	title = {An Unexpected Postvitrectomy Course.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {8},
	year = {2016},
	month = {2016 Aug 1},
	pages = {937-938},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.6117},
	author = {Thanos, Aristomenis and Modjtahedi, Bobeck S and Eliott, Dean}
}
@article {560176,
	title = {Retinal damage induced by mirror-reflected light from a laser pointer.},
	journal = {BMJ Case Rep},
	volume = {2015},
	year = {2015},
	month = {2015},
	abstract = {The safety of laser pointers is a major public health issue since class I and II laser pointers are available worldwide and used as toys by children despite several reports cautioning such use. Here we present the first case of retinal injury caused by the laser beam of a toy laser pointer operated by a school boy and directed via the rear-view mirror of a bus into the eye of the driver. This case emphasises the great importance of cautious and appropriate use of low-energy laser pointers. Laser pointers of any class should not be made available to children because they are unlikely to understand the risks of such lasers when using them in play.},
	issn = {1757-790X},
	doi = {10.1136/bcr-2015-210311},
	author = {Thanos, Solon and B{\"o}hm, Michael R R and Meyer Zu H{\"o}rste, Melissa and Schmidt, Peter-Fritz}
}
@article {560161,
	title = {Cotton-Wool Spots Associated With Mild Nonprogressive Visual Loss.},
	journal = {JAMA Ophthalmol},
	year = {2015},
	month = {2015 Oct 8},
	pages = {1-2},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.1967},
	author = {Thanos, Aristomenis and Esmaili, Daniel D and Eliott, Dean}
}
@article {1364556,
	title = {Evidence for baseline retinal pigment epithelium pathology in the Trp1-Cre mouse},
	journal = {Am J Pathol},
	volume = {180},
	number = {5},
	year = {2012},
	month = {2012 May},
	pages = {1917-27},
	abstract = {The increasing popularity of the Cre/loxP recombination system has led to the generation of numerous transgenic mouse lines in which Cre recombinase is expressed under the control of organ- or cell-specific promoters. Alterations in retinal pigment epithelium (RPE), a multifunctional cell monolayer that separates the retinal photoreceptors from the choroid, are prevalent in the pathogenesis of a number of ocular disorders, including age-related macular degeneration. To date, six transgenic mouse lines have been developed that target Cre to the RPE under the control of various gene promoters. However, multiple lines of evidence indicate that high levels of Cre expression can be toxic to mammalian cells. In this study, we report that in the Trp1-Cre mouse, a commonly used transgenic Cre strain for RPE gene function studies, Cre recombinase expression alone leads to RPE dysfunction and concomitant disorganization of RPE layer morphology, large areas of RPE atrophy, retinal photoreceptor dysfunction, and microglial cell activation in the affected areas. The phenotype described herein is similar to previously published reports of conditional gene knockouts that used the Trp1-Cre mouse, suggesting that Cre toxicity alone could account for some of the reported phenotypes and highlighting the importance of the inclusion of Cre-expressing mice as controls in conditional gene targeting studies.},
	keywords = {Animals, Atrophy, Disease Models, Animal, Electroretinography, Gene Expression Regulation, Integrases, Membrane Glycoproteins, Mice, Mice, Transgenic, Microglia, Microscopy, Electron, Oxidoreductases, Phenotype, Photoreceptor Cells, Vertebrate, Recombinant Fusion Proteins, Retinal Dystrophies, Retinal Pigment Epithelium},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2012.01.017},
	author = {Thanos, Aristomenis and Morizane, Yuki and Murakami, Yusuke and Giani, Andrea and Mantopoulos, Dimosthenis and Kayama, Maki and Roh, Miin and Michaud, Norman and Pawlyk, Basil and Sandberg, Michael and Young, Lucy H and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1351202,
	title = {Role of crystallins in ocular neuroprotection and axonal regeneration},
	journal = {Prog Retin Eye Res},
	volume = {42},
	year = {2014},
	month = {2014 Sep},
	pages = {145-61},
	abstract = {Neuroprotection is an emerging challenge in ophthalmology due to the particularly exposed location of retinal neurons and to the steadily increasing rate of intraocular surgical and pharmacological treatments applied to various eye diseases. Within few decades neuroprotection has developed from strongly contested approaches to being recognized and introduced as a potentially clinical application. One of the groups of putative substances for neuroprotection comprises αA- and αB-crystallins, which are types of heat-shock proteins and are considered to be molecular chaperones. The β/γ-crystallins form their own superfamily and are characterized as proteins with a distinct structure containing four Greek key motifs. Besides being abundant in the ocular lens, crystallins are also expressed in both the developing and mature retina. Crystallins are dramatically up-regulated in numerous retinal pathologies, including mechanical injury, ischemic insults, age-related macular degeneration, uveoretinitis, and diabetic retinopathy. Crystallins of the α family are thought to play a crucial role in retinal neuron survival and inflammation. Crystallins of the β/γ superfamily are also small proteins with a possible emerging role in retinal tissue remodeling and repair. One of the typical retinal diseases associated with crystallins is the experimental glaucomatous neuropathy that is characterized by their expression. Another typical retinal disease is the atrophy that occurs after mechanical injury to the optic nerve, which is associated with the need to regrow retinal axons. We have shown in regenerative models in\&nbsp;vivo and in\&nbsp;vitro that βB2-crystallin actively supports the regenerative growth of cut retinal axons, thereby offering targets for neuroprotective and regenerative treatments. In this review we discuss the discovery that βB2-crystallin is clearly up-regulated in the regenerating retina in\&nbsp;vitro. βB2-Crystallin is produced and secreted during axon elongation, while β/γ-crystallins promote axon growth both in\&nbsp;vivo and in\&nbsp;vitro by acting either directly by uptake into cells, or indirectly by enhancing the production of ciliary neurotrophic factor from astrocytes to synergistically promote axon regrowth. We also discuss methods to induce the continuous production of crystallins at the site of injury and repair based on the use of transfected neural progenitor cells. This review ultimately leads to the conclusion that the postinjury fate of neurons cannot be seen merely as inevitable, but instead should be regarded as a challenge to shaping the neuroprotective and regenerative conditions that promote cell survival and axon repair.},
	keywords = {Axons, Crystallins, Humans, Nerve Regeneration, Neurodegenerative Diseases, Retina, Retinal Diseases},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2014.06.004},
	author = {Thanos, Solon and B{\"o}hm, Michael R R and Meyer Zu H{\"o}rste, Melissa and Prokosch-Willing, Verena and Hennig, Maren and Bauer, Dirk and Heiligenhaus, Arndt}
}
@article {988031,
	title = {RETINAL VASCULAR TORTUOSITY AND EXUDATIVE RETINOPATHY IN A FAMILY WITH DYSKERATOSIS CONGENITA MASQUERADING AS FAMILIAL EXUDATIVE VITREORETINOPATHY.},
	journal = {Retin Cases Brief Rep},
	volume = {11 Suppl 1},
	year = {2017},
	pages = {S187-S190},
	abstract = {PURPOSE: To report a novel presentation of dyskeratosis congenita masquerading as familial exudative vitreoretinopathy. METHODS: Observational case series involving single family and literature review. RESULTS: A brother and sister were diagnosed with familial exudative vitreoretinopathy at ages 4 and 2, respectively. Both patients were managed with laser photocoagulation. Eight years after the initial presentation, both siblings developed pancytopenia secondary to bone marrow failure. Laboratory work-up revealed severely shortened telomere length in both patients, and genetic testing revealed a missense mutation in the gene that encodes the reverse transcriptase component of telomerase, confirming the diagnosis of dyskeratosis congenita. The father of both children was a carrier of the same mutation, who exhibited marked retinal vascular tortuosity of the second-order vessels. CONCLUSION: Dyskeratosis congenita is a severe multisystem disorder, which should be considered in cases of pediatric exudative retinopathies with concurrent signs and/or symptoms of bone marrow failure.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000430},
	author = {Thanos, Aristomenis and Todorich, Bozho and Hypes, Stephen M and Yonekawa, Yoshihiro and Thomas, Benjamin and Randhawa, Sandeep and Drenser, Kimberly A and Trese, Michael T}
}
@article {882996,
	title = {Role of Thyroxine in the Development of Keratoconus.},
	journal = {Cornea},
	year = {2016},
	month = {2016 Aug 24},
	abstract = {PURPOSE: Keratoconus (KC) is a corneal ectasia whose pathophysiology is still mostly unknown. We investigated whether thyroid gland dysfunction (TGD) is associated with the development of KC. METHODS: We first conducted an epidemiological study, examining the prevalence of TGD among patients with KC. Then, we compared tear thyroxine (T4) in TGD and immunohistochemical staining of its receptors (T4Rs) between patients with KC and controls. The significance of T4 for corneal metabolism was studied in organotypic tissue cultures from monkey corneas. RESULTS: We found that TGD prevalence among patients with KC is 13.6\%, which is higher than its prevalence in the general population (about 2\%). Tear T4 was higher in KC, and keratocyte T4Rs were elevated in KC compared with controls. Furthermore, core proteins such as collagen and cytokeratins were equally altered both in KC and in the cultured corneas substituted with T4. CONCLUSIONS: Our data implicate a crucial role of T4 in KC pathophysiology, which is most likely mediated by T4Rs.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000988},
	author = {Thanos, Solon and Oellers, Patrick and Meyer Zu H{\"o}rste, Melissa and Prokosch, Verena and Schlatt, Stefan and Seitz, Berthold and Gatzioufas, Zisis}
}
@article {1363213,
	title = {Aminoimidazole carboxamide ribonucleotide (AICAR) inhibits the growth of retinoblastoma in vivo by decreasing angiogenesis and inducing apoptosis},
	journal = {PLoS One},
	volume = {8},
	number = {1},
	year = {2013},
	month = {2013},
	pages = {e52852},
	abstract = {5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48\% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma.},
	keywords = {Aminoimidazole Carboxamide, Animals, Antineoplastic Agents, Apoptosis, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cyclins, Mice, Mice, Nude, Neoplasm Transplantation, Neovascularization, Pathologic, Retinoblastoma, Ribonucleotides, S Phase},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0052852},
	author = {Theodoropoulou, Sofia and Brodowska, Katarzyna and Kayama, Maki and Morizane, Yuki and Miller, Joan W and Gragoudas, Evangelos S and Vavvas, Demetrios G}
}
@article {504041,
	title = {Corneal Neuralgia after LASIK.},
	journal = {Optom Vis Sci},
	volume = {92},
	number = {9},
	year = {2015},
	month = {2015 Sep},
	pages = {e233-40},
	abstract = {PURPOSE: To illustrate that corneal neuralgia may be the basis for refractory dry eye syndrome after laser-assisted in situ keratomileusis (LASIK). METHODS: The methodology used is that of a retrospective medical record review of a small case series. RESULTS: Three male patients, aged 30 to 48 years, referred in 2012 for dry eye syndrome refractory to treatment within 1 year of LASIK or LASIK enhancement are reported. Each patient gave history of eye pain, light sensitivity, and difficulty with visual activities beginning within 2 months of LASIK or LASIK enhancement. Best-corrected visual acuity was 20/15 or 20/20 in each of the six eyes. Tear-centered models and metrics did not explain persistent symptoms, which was consistent with inadequate response to standard dry eye treatments used before referral and reported here. In vivo confocal microscopy was abnormal at presentation in each case and was followed over time. Treatments undertaken subsequent to referral included autologous serum tears (three cases), PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem) treatment (two cases), and systemic agents for pain, anxiety, or depression (three cases). By the end of 2013, at a mean of 23 months after LASIK or LASIK enhancement, symptoms improved in all three patients. CONCLUSIONS: Patients with persistent dry eye symptoms out of proportion to clinical signs after LASIK have a syndrome that may best be classified as corneal neuralgia. In vivo confocal microscopy can be informative as to the neuropathic basis of this condition. In keeping with current understanding of complex regional pain syndrome, early multimodal treatment directed toward reducing peripheral nociceptive signaling is warranted to avoid subsequent centralization and persistence of pain. Distinguishing this syndrome from typical post-LASIK dry eye remains a challenge.},
	issn = {1538-9235},
	doi = {10.1097/OPX.0000000000000652},
	author = {Theophanous, Christos and Jacobs, Deborah S and Hamrah, Pedram}
}
@article {1817296,
	title = {The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2-global current practice patterns for the management of Cytomegalovirus anterior uveitis},
	journal = {Eye (Lond)},
	volume = {38},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {68-75},
	abstract = {AIMS: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide.

METHODS: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform.

RESULTS: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3\%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85\% of experts). About half of the experts (48\%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15\% for topical treatment (selected by 70\% of experts) and oral valganciclovir for systemic treatment (78\% of experts). The majority of experts (77\%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1\% was the drug of choice (opted by 70\% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88\% of experts) and those with at least 2 episodes of CMV AU within a year (75-88\% of experts).

CONCLUSIONS: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.},
	keywords = {Antiviral Agents, Aqueous Humor, Cytomegalovirus, Cytomegalovirus Infections, Ganciclovir, Humans, Uveitis, Anterior},
	issn = {1476-5454},
	doi = {10.1038/s41433-023-02631-8},
	author = {Thng, Zheng Xian and Putera, Ikhwanuliman and Testi, Ilaria and Chan, Kevin and Westcott, Mark and Chee, Soon-Phaik and Dick, Andrew D and Kempen, John H and Bodaghi, Bahram and Thorne, Jennifer E and Barisani-Asenbauer, Talin and De Smet, Marc D and Smith, Justine R and McCluskey, Peter and Distia Nora, Rina La and Jabs, Douglas A and de Boer, Joke H and Sen, H Nida and Goldstein, Debra A and Khairallah, Moncef and Davis, Janet L and Rosenbaum, James T and Jones, Nicholas P and Nguyen, Quan Dong and Pavesio, Carlos and Agrawal, Rupesh and Gupta, Vishali}
}
@article {1517178,
	title = {COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {3},
	year = {2021},
	month = {2021 03},
	pages = {306-310},
	abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.},
	keywords = {COVID-19, Eye Diseases, Humans, Immunosuppression, Immunosuppressive Agents, Ophthalmology, Pharmaceutical Preparations, Practice Guidelines as Topic, SARS-CoV-2},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-316586},
	author = {Thng, Zheng Xian and De Smet, Marc D and Lee, Cecilia S and Gupta, Vishali and Smith, Justine R and McCluskey, Peter J and Thorne, Jennifer E and Kempen, John H and Zierhut, Manfred and Nguyen, Quan Dong and Pavesio, Carlos and Agrawal, Rupesh}
}
@article {1817291,
	title = {The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis},
	journal = {Eye (Lond)},
	volume = {38},
	number = {1},
	year = {2024},
	month = {2024 Jan},
	pages = {61-67},
	abstract = {AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide.

METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting >=75\% of agreement or IQR <= 1 when a Likert scale is used.

RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints.

CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.},
	keywords = {Atrophy, Herpes Simplex, Herpes Zoster, Herpes Zoster Ophthalmicus, Herpesvirus 3, Human, Humans, Simplexvirus, Uveitis, Uveitis, Anterior},
	issn = {1476-5454},
	doi = {10.1038/s41433-023-02630-9},
	author = {Thng, Zheng Xian and Putera, Ikhwanuliman and Testi, Ilaria and Chan, Kevin and Westcott, Mark and Chee, Soon-Phaik and Dick, Andrew D and Kempen, John H and Bodaghi, Bahram and Thorne, Jennifer E and Barisani-Asenbauer, Talin and De Smet, Marc D and Smith, Justine R and McCluskey, Peter and Distia Nora, Rina La and Jabs, Douglas A and de Boer, Joke H and Sen, H Nida and Goldstein, Debra A and Khairallah, Moncef and Davis, Janet L and Rosenbaum, James T and Jones, Nicholas P and Nguyen, Quan Dong and Pavesio, Carlos and Agrawal, Rupesh and Gupta, Vishali}
}
@article {1452960,
	title = {Congenital monocular elevation deficiency associated with a novel gene variant},
	journal = {Br J Ophthalmol},
	volume = {104},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {547-550},
	abstract = {BACKGROUND: The genetic basis of monocular elevation deficiency (MED) is unclear. It has previously been considered to arise due to a supranuclear abnormality. METHODS: Two brothers with MED were referred to Leicester Royal Infirmary, UK from the local opticians. Their father had bilateral ptosis and was unable to elevate both eyes, consistent with the diagnosis of congenital fibrosis of extraocular muscles (CFEOM). Candidate sequencing was performed in all family members. RESULTS: Both affected siblings (aged 7 and 12 years) were unable to elevate the right eye. Their father had bilateral ptosis, left esotropia and bilateral limitation of elevation. Chin up head posture was present in the older sibling and the father. Bell{\textquoteright}s phenomenon and vertical rotational vestibulo-ocular reflex were absent in the right eye for both children. Mild bilateral facial nerve palsy was present in the older sibling and the father. Both siblings had slight difficulty with tandem gait. MRI revealed hypoplastic oculomotor nerve. Left anterior insular focal cortical dysplasia was seen in the older sibling. Sequencing of revealed a novel heterozygous variant (c.1263G\&gt;C, p.E421D) segregating with the phenotype. This residue is in the C-terminal H12 α-helix of β-tubulin and is one of three putative kinesin binding sites. CONCLUSION: We show that familial MED can arise from a variant and could be considered a limited form of CFEOM. Neurological features such as mild facial palsy and cortical malformations can be present in patients with MED. Thus, in individuals with congenital MED, consideration may be made for mutation screening.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-314293},
	author = {Thomas, Mervyn G and Maconachie, Gail D E and Constantinescu, Cris S and Chan, Wai-Man and Barry, Brenda and Hisaund, Michael and Sheth, Viral and Kuht, Helen J and Dineen, Rob A and Harieaswar, Sreemathi and Engle, Elizabeth C and Gottlob, Irene}
}
@article {1782421,
	title = {Use of Yamane technique for secondary intraocular lens implantation following open globe injury},
	journal = {BMJ Case Rep},
	volume = {16},
	number = {11},
	year = {2023},
	month = {2023 Nov 21},
	abstract = {A woman in her 50s presented with suspected open globe injury (OGI) of the right eye after being hit with a high velocity piece of plastic. Visual acuity at the time of presentation was counting fingers in the affected eye. Slit lamp examination revealed a full thickness laceration of the cornea and a traumatic cataract. Primary corneal repair was performed and the patient was left aphakic after cataract removal. Secondary intraocular lens placement was deferred for 2 years, after which time a scleral-fixated intraocular lens was implanted using the Yamane technique. Postoperative visual acuity of 20/50 was achieved, with the vision limited by persistent diabetic macular oedema. Thus, this case of successful implantation of a secondary lens using the Yamane technique in a patient with prior corneal laceration and traumatic cataract highlights that the Yamane technique can result in visual improvement in patients with prior OGI.},
	keywords = {Cataract, Cataract Extraction, Corneal Injuries, Female, Humans, Lacerations, Lens Implantation, Intraocular, Lens, Crystalline, Lenses, Intraocular, Retrospective Studies},
	issn = {1757-790X},
	doi = {10.1136/bcr-2023-255995},
	author = {Thomas, Jonathan and Armstrong, Grayson}
}
@article {1319485,
	title = {Novel techniques of engineering 3D vasculature tissue for surgical procedures},
	journal = {Am J Surg},
	volume = {218},
	number = {1},
	year = {2019},
	month = {2019 Jul},
	pages = {235-236},
	issn = {1879-1883},
	doi = {10.1016/j.amjsurg.2018.06.004},
	author = {Thomas, Daniel and Singh, Deepti}
}
@article {1351203,
	title = {Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation},
	journal = {Eur J Hum Genet},
	volume = {22},
	number = {3},
	year = {2014},
	month = {2014 Mar},
	pages = {344-9},
	abstract = {Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation. },
	keywords = {Adolescent, Adult, Age of Onset, Aged, Cataract, Child, Chromosomes, Human, Pair 11, Eye Diseases, Hereditary, Eye Proteins, Female, Fovea Centralis, Genes, Dominant, Homeodomain Proteins, Humans, Lod Score, Male, Middle Aged, Mutation, Missense, Nystagmus, Congenital, Paired Box Transcription Factors, PAX6 Transcription Factor, Pedigree, Polymorphism, Single Nucleotide, Repressor Proteins},
	issn = {1476-5438},
	doi = {10.1038/ejhg.2013.162},
	author = {Thomas, Shery and Thomas, Mervyn G and Andrews, Caroline and Chan, Wai-Man and Proudlock, Frank A and McLean, Rebecca J and Pradeep, Archana and Engle, Elizabeth C and Gottlob, Irene}
}
@article {1263421,
	title = {Angiopoietin-1 is required for Schlemm{\textquoteright}s canal development in mice and humans},
	journal = {J Clin Invest},
	year = {2017},
	month = {2017 Nov 06},
	abstract = {Primary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemm{\textquoteright}s canal (SC) and the trabecular meshwork. We previously identified loss-of-function mutations in the angiopoietin (ANGPT) receptor TEK in families with PCG and showed that ANGPT/TEK signaling is essential for SC development. Here, we describe roles for the major ANGPT ligands in the development of the aqueous outflow pathway. We determined that ANGPT1 is essential for SC development, and that Angpt1-knockout mice form a severely hypomorphic canal with elevated intraocular pressure. By contrast, ANGPT2 was dispensable, although mice deficient in both Angpt1 and Angpt2 completely lacked SC, indicating that ANGPT2 compensates for the loss of ANGPT1. In addition, we identified 3 human subjects with rare ANGPT1 variants within an international cohort of 284 PCG patients. Loss of function in 2 of the 3 patient alleles was observed by functional analysis of ANGPT1 variants in a combined in silico, in vitro, and in vivo approach, supporting a causative role for ANGPT1 in disease. By linking ANGPT1 with PCG, these results highlight the importance of ANGPT/TEK signaling in glaucoma pathogenesis and identify a candidate target for therapeutic development.},
	issn = {1558-8238},
	doi = {10.1172/JCI95545},
	author = {Thomson, Benjamin R and Souma, Tomokazu and Tompson, Stuart W and Onay, Tuncer and Kizhatil, Krishnakumar and Siggs, Owen M and Feng, Liang and Whisenhunt, Kristina N and Yanovitch, Tammy L and Kalaydjieva, Luba and Azmanov, Dimitar N and Finzi, Simone and Tanna, Christine E and Hewitt, Alex W and Mackey, David A and Bradfield, Yasmin S and Souzeau, Emmanuelle and Javadiyan, Shari and Wiggs, Janey L and Pasutto, Francesca and Liu, Xiaorong and John, Simon W M and Craig, Jamie E and Jin, Jing and Young, Terri L and Quaggin, Susan E}
}
@article {935691,
	title = {Medication-Related Pseudotumor Cerebri Syndrome.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	pages = {134-143},
	abstract = {Pseudotumor cerebri syndrome refers to elevated intracranial pressure associated with papilledema without an identified etiology for intracranial hypertension. Over the past few decades, several medications have been described to be associated with this syndrome. We searched the literature for those case reports and series and evaluated the evidence for the association of such medications with pseudotumor cerebri syndrome.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228415},
	author = {Thon, Olga R and Gittinger, John W}
}
@article {1424819,
	title = {Periocular Triamcinolone vs. Intravitreal Triamcinolone vs. Intravitreal Dexamethasone Implant for the Treatment of Uveitic Macular Edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) Trial},
	journal = {Ophthalmology},
	volume = {126},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {283-295},
	abstract = {PURPOSE: To evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI). DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS: Patients with uveitic ME. METHODS: Patients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes. MAIN OUTCOME MEASURES: The primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included >=20\% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks. RESULTS: All treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23\%, 39\%, and 46\% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio [HR], 0.79; 99.87\% confidence interval [CI], 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87\% CI, 0.56-0.86) had larger reductions in CST than PTA (P \&lt; 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87\% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P \&lt; 0.004). The risk of having IOP >=24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95\% CI, 0.91-3.65 and HR, 2.52; 95\% CI, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups. CONCLUSIONS: Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.08.021},
	author = {Thorne, Jennifer E and Sugar, Elizabeth A and Holbrook, Janet T and Burke, Alyce E and Altaweel, Michael M and Vitale, Albert T and Acharya, Nisha R and Kempen, John H and Jabs, Douglas A and Multicenter Uveitis Steroid Treatment Trial Research Group}
}
@article {1351204,
	title = {Interactive multiple object tracking (iMOT)},
	journal = {PLoS One},
	volume = {9},
	number = {2},
	year = {2014},
	month = {2014},
	pages = {e86974},
	abstract = {We introduce a new task for exploring the relationship between action and attention. In this interactive multiple object tracking (iMOT) task, implemented as an iPad app, participants were presented with a display of multiple, visually identical disks which moved independently. The task was to prevent any collisions during a fixed duration. Participants could perturb object trajectories via the touchscreen. In Experiment 1, we used a staircase procedure to measure the ability to control moving objects. Object speed was set to 1{\textdegree}/s. On average participants could control 8.4 items without collision. Individual control strategies were quite variable, but did not predict overall performance. In Experiment 2, we compared iMOT with standard MOT performance using identical displays. Object speed was set to 2{\textdegree}/s. Participants could reliably control more objects (M = 6.6) than they could track (M = 4.0), but performance in the two tasks was positively correlated. In Experiment 3, we used a dual-task design. Compared to single-task baseline, iMOT performance decreased and MOT performance increased when the two tasks had to be completed together. Overall, these findings suggest: 1) There is a clear limit to the number of items that can be simultaneously controlled, for a given speed and display density; 2) participants can control more items than they can track; 3) task-relevant action appears not to disrupt MOT performance in the current experimental context.},
	keywords = {Adolescent, Adult, Analysis of Variance, Attention, Female, Humans, Male, Motion Perception, Neuropsychological Tests, Pattern Recognition, Visual, Psychomotor Performance, Task Performance and Analysis, Young Adult},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0086974},
	author = {Thornton, Ian M and B{\"u}lthoff, Heinrich H and Horowitz, Todd S and Rynning, Aksel and Lee, Seong-Whan}
}
@article {1538345,
	title = {Oral Miltefosine as Salvage Therapy for Refractory Acanthamoeba Keratitis},
	journal = {Am J Ophthalmol},
	volume = {223},
	year = {2021},
	month = {2021 Mar},
	pages = {75-82},
	abstract = {PURPOSE: To report a case series of patients with treatment-resistant Acanthamoeba keratitis (AK) using oral miltefosine, often as salvage therapy. DESIGN: Descriptive, retrospective multicenter case series. METHODS: We reviewed 15 patients with AK unresponsive to therapy who were subsequently given adjuvant systemic miltefosine between 2011 and 2017. The main outcome measures were resolution of infection, final visual acuity, tolerance of miltefosine, and clinical course of disease. RESULTS: All patients were treated with biguanides and/or diamidines or azoles without resolution of disease before starting miltefosine. Eleven of 15 patients retained count fingers or better vision, and all were considered disease free at last follow-up. Eleven of 15 patients had worsening inflammation with miltefosine, with 10 of them improving with steroids. Six patients received multiple courses of miltefosine. Most tolerated oral miltefosine well, with mild gastrointestinal symptoms as the most common systemic side effect. CONCLUSIONS: Oral miltefosine is a generally well-tolerated treatment adjuvant in patients with refractory AK. The clinician should be prepared for a steroid-responsive inflammatory response frequently encountered during the treatment course.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.09.048},
	author = {Thulasi, Praneetha and Saeed, Hajirah N and Rapuano, Christopher J and Hou, Joshua H and Appenheimer, Alpheus B and Chodosh, James and Kang, Joann J and Morrill, Amber M and Vyas, Neil and Zegans, Michael E and Zuckerman, Richard and Tu, Elmer Y}
}
@article {1078826,
	title = {Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory Response in Human Retinal Pigment Epithelial Cells},
	journal = {Sci Rep},
	volume = {7},
	number = {1},
	year = {2017},
	month = {2017 May 24},
	pages = {2329},
	abstract = {Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD.},
	issn = {2045-2322},
	doi = {10.1038/s41598-017-02407-7},
	author = {Tian, Bo and Al-Moujahed, Ahmad and Bouzika, Peggy and Hu, Yijun and Notomi, Shoji and Tsoka, Pavlina and Miller, Joan W and Lin, Haijiang and Vavvas, Demetrios G}
}
@article {1748366,
	title = {Self-supervised pseudo multi-class pre-training for unsupervised anomaly detection and segmentation in medical images},
	journal = {Med Image Anal},
	volume = {90},
	year = {2023},
	month = {2023 Dec},
	pages = {102930},
	abstract = {Unsupervised anomaly detection (UAD) methods are trained with normal (or healthy) images only, but during testing, they are able to classify normal and abnormal (or disease) images. UAD is an important medical image analysis (MIA) method to be applied in disease screening problems because the training sets available for those problems usually contain only normal images. However, the exclusive reliance on normal images may result in the learning of ineffective low-dimensional image representations that are not sensitive enough to detect and segment unseen abnormal lesions of varying size, appearance, and shape. Pre-training UAD methods with self-supervised learning, based on computer vision techniques, can mitigate this challenge, but they are sub-optimal because they do not explore domain knowledge for designing the pretext tasks, and their contrastive learning losses do not try to cluster the normal training images, which may result in a sparse distribution of normal images that is ineffective for anomaly detection. In this paper, we propose a new self-supervised pre-training method for MIA UAD applications, named Pseudo Multi-class Strong Augmentation via Contrastive Learning (PMSACL). PMSACL consists of a novel optimisation method that contrasts a normal image class from multiple pseudo classes of synthesised abnormal images, with each class enforced to form a dense cluster in the feature space. In the experiments, we show that our PMSACL pre-training improves the accuracy of SOTA UAD methods on many MIA benchmarks using colonoscopy, fundus screening and Covid-19 Chest X-ray datasets.},
	issn = {1361-8423},
	doi = {10.1016/j.media.2023.102930},
	author = {Tian, Yu and Liu, Fengbei and Pang, Guansong and Chen, Yuanhong and Liu, Yuyuan and Verjans, Johan W and Singh, Rajvinder and Carneiro, Gustavo}
}
@article {836986,
	title = {miR-17-3p Exacerbates Oxidative Damage in Human Retinal Pigment Epithelial Cells.},
	journal = {PLoS One},
	volume = {11},
	number = {8},
	year = {2016},
	month = {2016},
	pages = {e0160887},
	abstract = {Oxidative stress has been shown to contribute to the development of age-related macular degeneration (AMD). MicroRNAs (miRNA) are small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We showed miR-17-3p to be elevated in macular RPE cells from AMD patients and in ARPE-19 cells under oxidative stress. Transfection of miR-17-3p mimic in ARPE-19 induced cell death and exacerbated oxidative lethality that was alleviated by miR-17-3p inhibitor. The expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and thioredoxin reductase-2 (TrxR2) were suppressed by miR-17-3p mimic and reversed by miR-17-3p inhibitor. These results suggest miR-17-3p aggravates oxidative damage-induced cell death in human RPE cells, while miR-17-3p inhibitor acts as a potential protector against oxidative stress by regulating the expression of antioxidant enzymes.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0160887},
	author = {Tian, Bo and Maidana, Daniel E and Dib, Bernard and Miller, John B and Bouzika, Peggy and Miller, Joan W and Vavvas, Demetrios G and Lin, Haijiang}
}
@article {1405416,
	title = {Conjunctival Goblet Cells, the Overlooked Cells in Glaucoma Treatment},
	journal = {J Glaucoma},
	volume = {28},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {325-333},
	abstract = {Glaucoma is the leading cause of irreversible blindness worldwide. Although no definitive cure exists, lowering of the intraocular pressure decreases the rate of progression in the majority of patients with glaucoma. Antiglaucomatous treatment modalities consist predominantly of chronic use of eye drops. It has become increasingly evident that long-term exposure to eye drops has a significant impact on the ocular surface, and thereby on patient compliance and quality of life. Maintenance of the ocular surface is highly dependent on a stable tear film. Conjunctival goblet cells (GCs) of the ocular surface play an important role in providing the innermost mucin layer of the tear film and are essential for maintaining the ocular surface homeostasis. Recent studies have reported severe side effects of antiglaucomatous drops on GCs. In particular, a preservative containing antiglaucomatous drops have been shown to affect the viability and functions of the GCs. Furthermore, GC density has been suggested as a potential predictor of surgical outcome after filtration surgery. The present review provides an overview of the current literature on the impact of antiglaucomatous eye drops on GCs as well as the impact on the ocular surface. Moreover, the existing evidence of a possible association between GC density and glaucoma filtration surgery outcome is summarized. We conclude that prostaglandin analogs spare the conjunctival GCs more compared with other antiglaucomatous drops and that GCs may be a good predictor of surgical outcome after filtration surgery. Overall, given the multiple functions of GCs in the ocular surface homeostasis, dedicated strategies should be adopted to preserve this cell population during the course of glaucoma.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000001168},
	author = {Tiedemann, Daniel and Mouhammad, Zaynab A and Utheim, Tor P and Dartt, Darlene A. and Heegaard, Steffen and Petrovski, Goran and Kolko, Miriam}
}
@article {591206,
	title = {Visual Field Loss in a Case of Recurrent Cystic Craniopharyngioma During Concomitant Treatment With Pegylated Interferon α-2b.},
	journal = {J Pediatr Hematol Oncol},
	year = {2015},
	month = {2015 Nov 10},
	abstract = {A 13-year-old male with suprasellar cystic craniopharyngioma initially controlled with sequential subtotal resections and proton-beam irradiation was later treated with intracystic pegylated interferon α-2b due to progression and a lack of further surgical options. After initial successful control of recurrent cyst enlargement and stabilization of the ophthalmic examination, progressive and irreversible visual field loss ensued. Imaging revealed intracranial leakage from the intracystic catheter, and direct administration of interferon α-2b was discontinued. Given the recent interest in interferon α-2b, oncologists are advised to vigilantly monitor patients for signs of local toxicity that may result from unintended leakage during intracystic delivery.},
	issn = {1536-3678},
	doi = {10.1097/MPH.0000000000000468},
	author = {Tiedemann, Laura M and Manley, Peter and Smith, Edward R and Dagi, Linda R}
}
@article {280786,
	title = {Iatrogenic inferior oblique palsy: intentional disinsertion during transcaruncular approach to orbital fracture repair.},
	journal = {J AAPOS},
	year = {2014},
	month = {2014 Sep 27},
	abstract = {Hypotropia following orbital fracture repair is traditionally attributed to residual tissue entrapment, scarring, direct muscle injury, or damage to the branches of the oculomotor nerve serving the inferior oblique or inferior rectus muscles. We present a case of acquired hypotropia and incyclotropia that occurred following repair of an orbital fracture involving the floor and medial wall. In order to enable adequate visualization and treatment of the combined fractures, access via a transcaruncular approach and disinsertion of the inferior oblique muscle at its origin was necessary. Whereas the possibility of inferior oblique paresis due to repair of an orbital fracture via the transcaruncular approach has received some acknowledgment, there are no prior reports in the ophthalmic literature. Strabismus surgeons should be aware of this possibility when planning surgical correction of hypotropia and incyclotropia in similar cases.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2014.06.005},
	author = {Tiedemann, Laura M and Lefebvre, Daniel R and Wan, Michael J and Dagi, Linda R}
}
@article {1430541,
	title = {Small Benign Storiform Fibrous Tumor (Fibrous Histiocytoma) of the Conjunctival Substantia Propria in a Child: Review and Clarification of Biologic Behavior},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {5},
	year = {2019},
	month = {2019 Sep/Oct},
	pages = {495-502},
	abstract = {PURPOSE: A case of a small benign storiform fibrous tumor of the conjunctival substantia propria is described to clarify the category of fibrous histiocytoma. In addition, a comparison of the various spindle cell tumors of the conjunctival substantia propria is explored. METHODS: The patient underwent a complete tumor excision, and the specimen was analyzed by histopathologic and immunohistochemical investigations. RESULTS: A cellular mass, composed solely of spindle cells in a storiform pattern without a component of histiocytic cells, was found beneath an undisturbed nonkeratinizing squamous epithelium and was separated from the epithelium by a grenz zone of uninvolved collagen. The lesion was sharply demarcated but not encapsulated. The Masson trichrome stain revealed scant deposition of intercellular collagen. The reticulin stain displayed numerous and delicate wiry fibers between the tumor cells and encircling capillaries. The Alcian blue stain demonstrated faint positivity in the interstitium. Immunohistochemistry revealed positivity for vimentin, factor XIIIa, smooth muscle actin, CD10, and CD45. Negative stains were obtained for CD34, CD56, S100, desmin, and Ki67. CONCLUSIONS: The broad term of fibrous histiocytoma should be reserved for deep fibroblastic spindle cell tumors (e.g., those of the orbit) that display an aggressive behavior. More benign superficial spindle cell tumors of the dermis are now preferentially characterized as dermatofibromas. It is suggested that equally benign epibulbar tumors should no longer be designated as fibrous histiocytomas but rather as benign storiform fibrous tumors. Tumors completely composed of polygonal histiocytoid (epithelioid) cells that are CD34+ should be excluded from the benign storiform fibrous tumor category. Positive smooth muscle actin and factor XIIIa staining in conjunction with negative staining for CD34 and desmin in the current spindled tumor cells are findings consistent with those of cutaneous dermatofibromas. Both the epibulbar and dermal spindle cell lesions have displayed an indolent and nonaggressive behavior. Microscopically they contain a high proportion of dendrocytic stellate cells that are either factor XIIIa+ or XIIIa-. Given the anatomic differences between the dermis and conjunctiva, the term dermatofibroma is inappropriate for the current tumor; instead the term benign storiform fibrous tumor has been proposed for superficial tumors of the conjunctiva.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001355},
	author = {Tieger, Marisa G and Jakobiec, Frederick A and Ma, Lina and Wolkow, Natalie}
}
@article {1789086,
	title = {Review of Management and Outcomes of Delayed Repair Open Globe Injuries},
	journal = {Semin Ophthalmol},
	volume = {39},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {139-142},
	abstract = {The standard of care for open globe injuries is prompt surgical closure, as delay in repair is a reported risk factor for post-traumatic endophthalmitis and is associated with worse visual outcomes. This article serves as a review of the current management and outcomes of open globe injuries repaired greater than 24 hours from the time of injury, specifically evaluating the rates of endophthalmitis in cases with and without intraocular foreign bodies, visual outcomes and rates of primary enucleation or evisceration.},
	keywords = {Endophthalmitis, Eye Foreign Bodies, Eye Injuries, Penetrating, Humans, Retrospective Studies, Risk Factors, Visual Acuity},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2286015},
	author = {Tieger, Marisa and Armstrong, Grayson W and Eliott, Dean}
}
@article {1761866,
	title = {SPONTANEOUS CLOSURE AND RECURRENT OPENING TIMES TWO OF A MACULAR HOLE IN A SURGICALLY NAIVE EYE},
	journal = {Retin Cases Brief Rep},
	volume = {17},
	number = {5},
	year = {2023},
	month = {2023 Sep 01},
	pages = {581-583},
	abstract = {PURPOSE: To report a case of an idiopathic macular hole with recurrent opening and spontaneous closure in a surgically naive eye. METHODS: A retrospective review of medical records was performed in addition to a review of the current literature. RESULTS: An 82-year-old man was referred for the management of a full-thickness macular hole in the right eye. Visual acuity was 20/60, and dilated fundus examination was notable for a posterior vitreous detachment, macular hole, and mild epiretinal membrane. Optical coherence tomography confirmed the presence of a full-thickness macular hole. The patient declined surgical intervention and elected to observe. Five weeks later, optical coherence tomography confirmed spontaneous closure. One year later, a recurrent partial thickness outer retinal hole was noted on dilated fundus examination and optical coherence tomography that subsequently spontaneously closed for the second time. The following year, the patient represented with a new scotoma and metamorphopsia and was found to have a full-thickness macular hole. This time the patient was elected for surgical intervention (25-gauge pars plana vitrectomy, epiretinal membrane peel, and 14\% C3F8), resulting in closure of the macular hole and improvement in visual acuity to 20/25+1. CONCLUSION: This case highlights a rare presentation of a see-saw pattern of opening and closing of a macular hole in a treatment-naive eye. The presence of a posterior vitreous detachment and epiretinal membrane suggests that other factors than anterior-posterior and tangential traction may be a contributing in the formation and closure of idiopathic macular holes.},
	keywords = {Aged, 80 and over, Epiretinal Membrane, Fundus Oculi, Humans, Male, Retinal Perforations, Scotoma, Vitreous Detachment},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001244},
	author = {Tieger, Marisa G and Kim, Leo A and Vavvas, Demetrios G}
}
@article {1586195,
	title = {Microvasculopathy in Lyme-Associated Papillitis Revealed by Optical Coherence Tomographic Angiography},
	journal = {J Neuroophthalmol},
	year = {2021},
	month = {2021 Mar 23},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001208},
	author = {Tieger, Marisa G and Miller, John B and Gaier, Eric D}
}
@article {1511503,
	title = {Impact of contact versus non-contact wide-angle viewing systems on outcomes of primary retinal detachment repair (PRO study report number 5)},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {3},
	year = {2021},
	month = {2021 Mar},
	pages = {410-413},
	abstract = {BACKGROUND/AIMS: Vitrectomy to repair retinal detachment is often performed with either non-contact wide-angle viewing systems or wide-angle contact viewing systems. The purpose of this study is to assess whether the viewing system used is associated with any differences in surgical outcomes of vitrectomy for primary non-complex retinal detachment repair. METHODS: This is a multicenter, interventional, retrospective, comparative study. Eyes that underwent non-complex primary retinal detachment repair by either pars plana vitrectomy (PPV) alone or in combination with scleral buckle/PPV in 2015 were evaluated. The viewing system at the time of the retinal detachment repair was identified and preoperative patient characteristics, intraoperative findings and postoperative outcomes were recorded. RESULTS: A total of 2256 eyes were included in our analysis. Of those, 1893 surgeries used a non-contact viewing system, while 363 used a contact lens system. There was no statistically significant difference in single surgery anatomic success at 3 months (p=0.72), or final anatomic success (p=0.40). Average postoperative visual acuity for the contact-based cases was logMAR 0.345 (20/44 Snellen equivalent) compared with 0.475 (20/60 Snellen equivalent) for non-contact (p=0.001). After controlling for numerous confounding variables in multivariable analysis, viewing system choice was no longer statistically significant (p=0.097). CONCLUSION: There was no statistically significant difference in anatomic success achieved for primary retinal detachment repair when comparing non-contact viewing systems to contact lens systems. Postoperative visual acuity was better in the contact-based group but this was not statistically significant when confounding factors were controlled for.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-315948},
	author = {Tieger, Marisa G and Rodriguez, Marianeli and Wang, Jay C and Obeid, Anthony and Ryan, Claire and Gao, Xinxiao and Kakulavarapu, Srividya and Mardis, Patrick J and Madhava, Malika L and Maloney, Sean M and Adika, Adam Z and Peddada, Krishi V and Sioufi, Kareem and Stefater, James A and Forbes, Nora J and Capone, Antonio and Emerson, Geoffrey G and Joseph, Daniel P and Regillo, Carl and Hsu, Jason and Gupta, Omesh and Eliott, Dean and Ryan, Edwin H and Yonekawa, Yoshihiro}
}
@article {1517168,
	title = {Artificial intelligence for anterior segment diseases: Emerging applications in ophthalmology},
	journal = {Br J Ophthalmol},
	volume = {105},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {158-168},
	abstract = {With the advancement of computational power, refinement of learning algorithms and architectures, and availability of big data, artificial intelligence (AI) technology, particularly with machine learning and deep learning, is paving the way for {\textquoteright}intelligent{\textquoteright} healthcare systems. AI-related research in ophthalmology previously focused on the screening and diagnosis of posterior segment diseases, particularly diabetic retinopathy, age-related macular degeneration and glaucoma. There is now emerging evidence demonstrating the application of AI to the diagnosis and management of a variety of anterior segment conditions. In this review, we provide an overview of AI applications to the anterior segment addressing keratoconus, infectious keratitis, refractive surgery, corneal transplant, adult and paediatric cataracts, angle-closure glaucoma and iris tumour, and highlight important clinical considerations for adoption of AI technologies, potential integration with telemedicine and future directions.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2019-315651},
	author = {Ting, Darren Shu Jeng and Foo, Valencia Hx and Yang, Lily Wei Yun and Sia, Josh Tjunrong and Ang, Marcus and Lin, Haotian and Chodosh, James and Mehta, Jodhbir S and Ting, Daniel Shu Wei}
}
@article {1655707,
	title = {Achieving diagnostic excellence for infectious keratitis: A future roadmap},
	journal = {Front Microbiol},
	volume = {13},
	year = {2022},
	month = {2022},
	pages = {1020198},
	issn = {1664-302X},
	doi = {10.3389/fmicb.2022.1020198},
	author = {Ting, Darren S J and Chodosh, James and Mehta, Jodhbir S}
}
@article {1789166,
	title = {An Adjustable Magnetic Levator Prosthesis for Customizable Eyelid Reanimation in Severe Blepharoptosis II: Randomized Evaluation of Angular Translation},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {12},
	year = {2023},
	month = {2023 Dec 01},
	pages = {1},
	abstract = {PURPOSE: Examine the effect of force modulation via angular translation of a static magnetic field for customizable treatment of severe blepharoptosis. METHODS: Prototype adjustable-force magnetic levator prostheses (aMLP) consisted of a spectacle-mounted magnet in rotatable housing and small eyelid-attached magnets embedded in a biocompatible polymer. Interpalpebral fissure (IPF) of 17 participants with severe blepharoptosis was continuously measured for one minute at five spectacle magnet angles, with order randomized and participant and data analyst masked. The hypothesis that angular position affected opening IPF (o-IPF), minimum blink IPF (m-IPF), and comfort ratings (1-10) was tested. RESULTS: The aMLP improved o-IPF from 4.5 mm without the device to 6.2 mm on the lowest force setting (P \&lt; 0.001) and 7.1 mm on the highest setting (P \&lt; 0.001) and allowed for complete volitional blink regardless of setting (average m-IPF 0.4 mm and no change with aMLP; P = 0.76). Spontaneous blink without the device (2.0 mm) was affected on the highest force setting (m-IPF 3.9 mm; P \&lt; 0.001) but only marginally so on the lowest setting (3.0 mm; P = 0.06). Comfort (7.6/10) did not vary with the angle (P \&gt; 0.36). Profile analysis found substantial individual responses to angle (P \&lt; 0.001), confirming the value of customization. CONCLUSIONS: Angular translation provided adjustable force, which had a statistically and clinically meaningful impact on eye opening and the completeness of the spontaneous blink. This quantitative evidence supports continued use of the angular translation mechanism for force adjustment in the customizable magnetic correction of severe blepharoptosis. TRANSLATIONAL RELEVANCE: Evidence for the benefit of customizable magnetic force via angular translation in a larger sample of participants than reported previously.},
	keywords = {Blepharoptosis, Eyelids, Humans, Magnetic Phenomena, Prostheses and Implants},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.12.1},
	author = {Tirandazi, Pooyan and Nadeau, Melanie and Woods, Russell L and Paschalis, Eleftherios I and Houston, Kevin E}
}
@article {1179196,
	title = {Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura},
	journal = {Dev Cell},
	volume = {42},
	number = {5},
	year = {2017},
	month = {2017 Sep 11},
	pages = {445-461.e5},
	abstract = {Dural cerebral veins (CV) are required for cerebrospinal fluid reabsorption and brain homeostasis, but mechanisms that regulate their growth and remodeling are unknown. We report molecular and cellular processes that regulate dural CV development in mammals and describe venous malformations in humans with craniosynostosis and TWIST1 mutations that are recapitulated in mouse models. Surprisingly, Twist1 is dispensable in endothelial cells but required for specification of osteoprogenitor cells that differentiate into preosteoblasts that produce bone morphogenetic proteins (BMPs). Inactivation of Bmp2 and Bmp4 in preosteoblasts and periosteal dura causes skull and CV malformations, similar to humans harboring TWIST1 mutations. Notably, arterial development appears normal, suggesting that morphogens from the skull and dura establish optimal venous networks independent from arterial influences. Collectively, our work establishes a paradigm whereby CV malformations result from primary or secondary loss of\&nbsp;paracrine BMP signaling from preosteoblasts and dura, highlighting unique cellular interactions\&nbsp;that influence tissue-specific angiogenesis in mammals.},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2017.07.027},
	author = {Tischfield, Max A and Robson, Caroline D and Gilette, Nicole M and Chim, Shek Man and Sofela, Folasade A and DeLisle, Michelle M and Gelber, Alon and Barry, Brenda J and MacKinnon, Sarah and Dagi, Linda R and Nathans, Jeremy and Engle, Elizabeth C}
}
@article {1598038,
	title = {Afferent and Efferent Neuro-Ophthalmic Complications of Coronavirus Disease 19},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {2},
	year = {2021},
	month = {2021 06 01},
	pages = {154-165},
	abstract = {PURPOSE: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19) documented in the literature thus far. METHODS: The PubMed and Google Scholar databases were searched using the keywords: Neuro-Ophthalmology, COVID-19, SARS-CoV-2, and coronavirus. A manual search through reference lists of relevant articles was also performed. RESULTS/CONCLUSIONS: The literature on COVID-associated neuro-ophthalmic disease continues to grow. Afferent neuro-ophthalmic complications associated with COVID-19 include optic neuritis, papillophlebitis, papilledema, visual disturbance associated with posterior reversible encephalopathy syndrome, and vision loss caused by stroke. Efferent neuro-ophthalmic complications associated with COVID-19 include cranial neuropathies, Miller Fisher syndrome, Adie{\textquoteright}s pupils, ocular myasthenia gravis, nystagmus and eye movement disorders. Proposed mechanisms of neurologic disease include immunologic upregulation, vasodilation and vascular permeability, endothelial dysfunction, coagulopathy, and direct viral neurotropism. When patients present to medical centers with new onset neuro-ophthalmic conditions during the pandemic, COVID-19 infection should be kept on the differential.},
	keywords = {COVID-19, Humans, Optic Neuritis, Pandemics, Posterior Leukoencephalopathy Syndrome, SARS-CoV-2},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001276},
	author = {Tisdale, Alanna K and Dinkin, Marc and Chwalisz, Bart K}
}
@article {1549011,
	title = {Neuro-ophthalmic manifestations of coronavirus disease 19},
	journal = {Curr Opin Ophthalmol},
	volume = {31},
	number = {6},
	year = {2020},
	month = {2020 Nov},
	pages = {489-494},
	abstract = {PURPOSE OF REVIEW: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19), documented in the literature thus far. RECENT FINDINGS: A small but growing literature documents cases of new onset neuro-ophthalmic disease, in the setting of COVID-19 infection. Patients with COVID-19 have experienced acute onset vision loss, optic neuritis, cranial neuropathies, and Miller Fisher syndrome. In addition, COVID-19 increases the risk of cerebrovascular diseases that can impact the visual system. SUMMARY: The literature on COVID-19 continues to evolve. Although COVID-19 primarily impacts the respiratory system, there are several reports of new onset neuro-ophthalmic conditions in COVID-infected patients. When patients present with new onset neuro-ophthalmic issues, COVID-19 should be kept on the differential. Testing for COVID-19 should be considered, especially when fever or respiratory symptoms are also present. When screening general patients for COVID-19-associated symptoms, frontline physicians can consider including questions about diplopia, eye pain, pain with extraocular movements, decreased vision, gait issues, and other neurologic symptoms. The presence of these symptoms may increase the overall probability of viral infection, especially when fever or respiratory symptoms are present. More research is needed to establish a causal relationship between COVID-19 and neuro-ophthalmic disease, and better understand pathogenesis.},
	keywords = {Animals, Betacoronavirus, Clinical Laboratory Techniques, Coronavirus Infections, Diplopia, Eye Pain, Humans, Optic Neuritis, Pandemics, Pneumonia, Viral},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000707},
	author = {Tisdale, Alanna K and Chwalisz, Bart K}
}
@article {1748381,
	title = {Neuro-ophthalmic complications of varicella-zoster virus},
	journal = {Curr Opin Ophthalmol},
	volume = {34},
	number = {6},
	year = {2023},
	month = {2023 Nov 01},
	pages = {470-475},
	abstract = {PURPOSE OF REVIEW: This review broadly describes recent neuro-ophthalmic manifestations of varicella-zoster virus (VZV) reported in literature. RECENT FINDINGS: Despite varicella vaccination, the incidence of herpes zoster continues to rise, potentially leading to devastating consequences when ocular complications occur.A small but growing literature documents cases of retinal disease because of varicella reactivation after SARS-CoV-2 vaccination, ischemic optic neuropathy occurring during herpes zoster ophthalmicus, VZV-induced orbital apex syndrome, and immune-mediated ocular complications in patients with prior neuro-ophthalmic manifestations of VZV. SUMMARY: It is important for clinicians to keep abreast of the diverse neuro-ophthalmic manifestations of VZV as early diagnosis and treatment often lead to better visual outcomes.},
	keywords = {Chickenpox, COVID-19, COVID-19 Vaccines, Herpesvirus 3, Human, Humans, SARS-CoV-2},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000996},
	author = {Tofade, Toluwalase O and Chwalisz, Bart K}
}
@article {1460359,
	title = {Patterns of Uveitis among Patients Attending Jimma University Department of Ophthalmology, Jimma, Ethiopia},
	journal = {Ocul Immunol Inflamm},
	volume = {28},
	number = {7},
	year = {2020},
	month = {2020 Oct 02},
	pages = {1109-1115},
	abstract = {: Uveitis is an important cause of blindness and ocular morbidity in the world. The patterns of uveitis have not been well characterized in sub-Saharan Africa. : To describe the characteristics of uveitis among patients presenting to Jimma University Department of Ophthalmology (JUDO) from July 2013 to December 2014. : This hospital-based prospective cross-sectional study included all new uveitis patients visiting JUDO outpatient department during the study period. : Among 98 patients diagnosed with uveitis, anterior uveitis was found in 74.5\% of patients. Majority of the patients, 83.7\%, had unilateral uveitis. A uveitis syndrome was identified in 22.5\% of cases; of these 15 (68.2\%) were infectious. Herpes simplex uveitis was the commonest infectious cause (53.3\%) while Toxoplasmosis was the most common cause of posterior uveitis (60\%). : Anterior uveitis was the most common pattern found among uveitis patients. Herpes simplex and toxoplasmic chorioretinitis were the most common-identified infectious causes.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2019.1644348},
	author = {Tolesa, Kumale and Abateneh, Aemero and Kempen, John H and Gelaw, Yeshigeta}
}
@article {1677786,
	title = {Open-Globe Injury Repairs in the American Academy of Ophthalmology IRIS{\textregistered} Registry 2014 - 2018: Incidence, Risk Factors, and Visual Outcomes},
	journal = {Ophthalmology},
	volume = {130},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {812-821},
	abstract = {PURPOSE: To estimate incidence and evaluate demographic risk factors and visual acuity (VA) outcomes of open-globe injuries requiring surgical repair in the IRIS{\textregistered} Registry (Intelligent Research in Sight). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with open-globe injury repairs (OGRs) were identified by Current Procedural Terminology codes (65275, 65280, 65285, 65286, 65235, 65260, and 65265) from 2014 through 2018 in the IRIS Registry. METHODS: Logistic regression models adjusting for age, sex, race, ethnicity, United States region, concurrent and subsequent surgeries, and baseline VA. MAIN OUTCOME MEASURES: Outcomes included annual and 5-year incidence rates per 100 000 people and factors associated with OGR, VA better than 20/40, and VA of 20/200 or worse at final follow-up (3-12 months after OGR). RESULTS: Thirteen thousand seven hundred sixty-six OGRs were identified; 5-year cumulative incidence was 28.0 per 100 000 patients. Open-globe repair was associated with age 21 to 40 years compared with younger than 21 years (odds ratio [OR], 1.6; 95\% confidence interval [CI], 1.5-1.7]), male sex (OR, 2.8; 95\% CI, 2.7-2.9), Black versus White race (OR, 1.3; 95\% CI, 1.2-1.4), Hispanic versus non-Hispanic ethnicity (OR, 1.7; 95\% CI, 1.6-1.8), and South (OR, 1.4; 95\% CI, 1.3-1.5) and West (OR, 1.3; 95\% CI, 1.2-1.4) versus Midwest regions and associated inversely with Asian versus White race (OR, 0.6; 95\% CI, 0.6-0.7). Visual acuity outcomes, analyzed in a subset of 2966 patients with VA data available, showed vision impairment (VA \&lt; 20/40) at final follow-up was associated with VA of 20/200 or worse at presentation (20/200 better than 20/40; OR, 11.1; 95\% CI, 8.0-15.7), older age (e.g., \&gt; 80 years vs. \&lt; 21 years; OR, 5.8; 95\% CI, 3.2-10.7), and Black versus White race (OR, 1.8; 95\% CI, 1.3-2.6). Risk factors were similar for VA of 20/200 or worse after OGR. Among the 1063 patients undergoing OGR with VA of 20/200 or worse at presentation, VA did not improve to better than 20/200 at follow-up in 35\% of patients (1063/2996). CONCLUSIONS: Our findings bring to light racial disparities in risk of OGR and poor visual outcomes that warrant further exploration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Adult, Eye Injuries, Humans, Incidence, Male, Ophthalmology, Registries, Retrospective Studies, Risk Factors, United States, Young Adult},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.03.002},
	author = {Tomaiuolo, Maurizio and Woreta, Fasika A and Li, Alexander and Yonekawa, Yoshihiro and Zhang, Qiang Ed and Sharpe, James E and Zafar, Sidra and Syed, Zeba A and Ramesh, Sathyadeepak and Lorch, Alice C and Hall, Nathan E and Shah, Ankoor S and Justin, Grant A and Hyman, Leslie and IRIS{\textregistered} Registry Analytic Center Consortium}
}
@article {1538341,
	title = {Vitreous metabolomics profiling of proliferative diabetic retinopathy},
	journal = {Diabetologia},
	volume = {64},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {70-82},
	abstract = {AIMS/HYPOTHESIS: Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. METHODS: We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80\&nbsp;years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. RESULTS: We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate \&lt;0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). CONCLUSIONS/INTERPRETATION: These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.},
	issn = {1432-0428},
	doi = {10.1007/s00125-020-05309-y},
	author = {Tomita, Yohei and Cagnone, Gael and Fu, Zhongjie and Cakir, Bertan and Kotoda, Yumi and Asakage, Masaki and Wakabayashi, Yoshihiro and Hellstr{\"o}m, Ann and Joyal, Jean-S{\'e}bastien and Talukdar, Saswata and Smith, Lois E H and Usui, Yoshihiko}
}
@article {1498256,
	title = {Free fatty acid receptor 4 activation protects against choroidal neovascularization in mice},
	journal = {Angiogenesis},
	volume = {23},
	number = {3},
	year = {2020},
	month = {2020 Aug},
	pages = {385-394},
	abstract = {To examine whether free fatty acid receptor 4 (FFAR4) activation can protect against choroidal neovascularization (CNV), which is a common cause of blindness, and to elucidate the mechanism underlying the inhibition, we used the mouse model of laser-induced CNV to mimic angiogenic aspects of age-related macular degeneration (AMD). Laser-induced CNV was compared between groups treated with an FFAR4 agonist or vehicle, and between FFAR4 wild-type (Ffar4) and knock out (Ffar4) mice on a C57BL/6J/6N background. The ex vivo choroid-sprouting assay, including primary retinal pigment epithelium (RPE) and choroid, without retina was used to investigate whether FFAR4 affects choroidal angiogenesis. Western blotting for pNF-kB/NF-kB and qRT-PCR for Il-6, Il-1β, Tnf-α, Vegf, and Nf-kb were used to examine the influence of FFAR4 on inflammation, known to influence CNV. RPE isolated from Ffar4 and Ffar4 mice were used to assess RPE contribution to inflammation. The FFAR4 agonist suppressed laser-induced CNV in C57BL/6J mice, and CNV increased in Ffar4 compared to Ffar4 mice. We showed that the FFAR4 agonist acted through the FFAR4 receptor. The FFAR4 agonist suppressed mRNA expression of inflammation markers (Il-6, Il-1β) via the NF-kB pathway in the retina, choroid, RPE complex. The FFAR4 agonist suppressed neovascularization in the choroid-sprouting ex vivo assay and FFAR4 deficiency exacerbated sprouting. Inflammation markers were increased in primary RPE cells of Ffar4 mice compared with Ffar4 RPE. In this mouse model, the FFAR4 agonist suppressed CNV, suggesting FFAR4 to be a new molecular target to reduce pathological angiogenesis in CNV.},
	issn = {1573-7209},
	doi = {10.1007/s10456-020-09717-x},
	author = {Tomita, Yohei and Cakir, Bertan and Liu, Chi-Hsiu and Fu, Zhongjie and Huang, Shuo and Cho, Steve S and Britton, William R and Sun, Ye and Puder, Mark and Hellstr{\"o}m, Ann and Talukdar, Saswata and Smith, Lois E H}
}
@article {1528416,
	title = {An Ex Vivo Choroid Sprouting Assay of Ocular Microvascular Angiogenesis},
	journal = {J Vis Exp},
	number = {162},
	year = {2020},
	month = {2020 Aug 06},
	abstract = {Pathological choroidal angiogenesis, a salient feature of age-related macular degeneration, leads to vision impairment and blindness. Endothelial cell (EC) proliferation assays using human retinal microvascular endothelial cells (HRMECs) or isolated primary retinal ECs are widely used in vitro models to study retinal angiogenesis. However, isolating pure murine retinal endothelial cells is technically challenging and retinal ECs may have different proliferation responses than choroidal endothelial cells and different cell/cell interactions. A highly reproducible ex vivo choroidal sprouting assay as a model of choroidal microvascular proliferation was developed. This model includes the interaction between choroid vasculature (EC, macrophages, pericytes) and retinal pigment epithelium (RPE). Mouse RPE/choroid/scleral explants are isolated and incubated in growth-factor-reduced basal membrane extract (BME) (day 0). Medium is changed every other day and choroid sprouting is quantified at day 6. The images of individual choroid explant are taken with an inverted phase microscope and the sprouting area is quantified using a semi-automated macro plug-in to the ImageJ software developed in this lab. This reproducible ex vivo choroidal sprouting assay can be used to assess compounds for potential treatment and for microvascular disease research to assess pathways involved in choroidal micro vessel proliferation using wild type and genetically modified mouse tissue.},
	issn = {1940-087X},
	doi = {10.3791/61677},
	author = {Tomita, Yohei and Shao, Zhuo and Cakir, Bertan and Kotoda, Yumi and Fu, Zhongjie and Smith, Lois E H}
}
@article {1490443,
	title = {Long-Acting FGF21 Inhibits Retinal Vascular Leakage in In Vivo and In Vitro Models},
	journal = {Int J Mol Sci},
	volume = {21},
	number = {4},
	year = {2020},
	month = {2020 Feb 11},
	abstract = {The aim of the current study was to investigate the impact of long-acting fibroblast growth factor 21 (FGF21) on retinal vascular leakage utilizing machine learning and to clarify the mechanism underlying the protection. To assess the effect on retinal vascular leakage, C57BL/6J mice were pre-treated with long-acting FGF21 analog or vehicle (Phosphate Buffered Saline; PBS) intraperitoneally (i.p.) before induction of retinal vascular leakage with intravitreal injection of mouse (m) vascular endothelial growth factor 164 (VEGF164) or PBS control. Five hours after mVEGF164 injection, we retro-orbitally injected Fluorescein isothiocyanate (FITC) -dextran and quantified fluorescence intensity as a readout of vascular leakage, using the Image Analysis Module with a machine learning algorithm. In FGF21- or vehicle-treated primary human retinal microvascular endothelial cells (HRMECs), cell permeability was induced with human (h) VEGF165 and evaluated using FITC-dextran and trans-endothelial electrical resistance (TEER). Western blots for tight junction markers were performed. Retinal vascular leakage in vivo was reduced in the FGF21 versus vehicle- treated mice. In HRMECs in vitro, FGF21 versus vehicle prevented hVEGF-induced increase in cell permeability, identified with FITC-dextran. FGF21 significantly preserved TEER compared to hVEGF. Taken together, FGF21 regulates permeability through tight junctions; in particular, FGF21 increases Claudin-1 protein levels in hVEGF-induced HRMECs. Long-acting FGF21 may help reduce retinal vascular leakage in retinal disorders and machine learning assessment can help to standardize vascular leakage quantification.},
	issn = {1422-0067},
	doi = {10.3390/ijms21041188},
	author = {Tomita, Yohei and Fu, Zhongjie and Wang, Zhongxiao and Cakir, Bertan and Cho, Steve S and Britton, William and Sun, Ye and Hellstr{\"o}m, Ann and Talukdar, Saswata and Smith, Lois E H}
}
@article {1538311,
	title = {PPARα Agonist Oral Therapy in Diabetic Retinopathy},
	journal = {Biomedicines},
	volume = {8},
	number = {10},
	year = {2020},
	month = {2020 Oct 19},
	abstract = {Diabetic retinopathy (DR) is an eye condition that develops after chronically poorly-managed diabetes, and is presently the main cause for blindness on a global scale. Current treatments for DR such as laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and vitreoretinal surgery are only applicable at the late stages of DR and there are possibilities of significant adverse effects. Moreover, the forms of treatment available for DR are highly invasive to the eyes. Safer and more effective pharmacological treatments are required for DR treatment, in particular at an early stage. In this review, we cover recently investigated promising oral pharmacotherapies, the methods of which are safer, easier to use, patient-friendly and pain-free, in clinical studies. We especially focus on peroxisome proliferator-activator receptor alpha (PPARα) agonists in which experimental evidence suggests PPARα activation may be closely related to the attenuation of vascular damages, including lipid-induced toxicity, inflammation, an excess of free radical generation, endothelial dysfunction and angiogenesis. Furthermore, oral administration of selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) agonists may induce hepatic fibroblast growth factor 21 expression, indirectly resulting in retinal protection in animal studies. Our review will enable more comprehensive approaches for understanding protective roles of PPARα for the prevention of DR development.},
	issn = {2227-9059},
	doi = {10.3390/biomedicines8100433},
	author = {Tomita, Yohei and Lee, Deokho and Tsubota, Kazuo and Kurihara, Toshihide}
}
@article {1623353,
	title = {M{\"u}ller glial responses compensate for degenerating photoreceptors in retinitis pigmentosa},
	journal = {Exp Mol Med},
	year = {2021},
	month = {2021 Nov 19},
	abstract = {Photoreceptor degeneration caused by genetic defects leads to retinitis pigmentosa, a rare disease typically diagnosed in adolescents and young adults. In most cases, rod loss occurs first, followed by cone loss as well as altered function in cells connected to photoreceptors directly or indirectly. There remains a gap in our understanding of retinal cellular responses to photoreceptor abnormalities. Here, we utilized single-cell transcriptomics to investigate cellular responses in each major retinal cell type in retinitis pigmentosa model (P23H) mice vs. wild-type littermate mice. We found a significant decrease in the expression of genes associated with phototransduction, the inner/outer segment, photoreceptor cell cilium, and photoreceptor development in both rod and cone clusters, in line with the structural changes seen with immunohistochemistry. Accompanying this loss was a significant decrease in the expression of genes involved in metabolic pathways and energy production in both rods and cones. We found that in the M{\"u}ller glia/astrocyte cluster, there was a significant increase in gene expression in pathways involving photoreceptor maintenance, while concomitant decreases were observed in rods and cones. Additionally, the expression of genes involved in mitochondrial localization and transport was increased in the M{\"u}ller glia/astrocyte cluster. The M{\"u}ller glial compensatory increase in the expression of genes downregulated in photoreceptors suggests that M{\"u}ller glia adapt their transcriptome to support photoreceptors and could be thought of as general therapeutic targets to protect against retinal degeneration.},
	issn = {2092-6413},
	doi = {10.1038/s12276-021-00693-w},
	author = {Tomita, Yohei and Qiu, Chenxi and Bull, Edward and Allen, William and Kotoda, Yumi and Talukdar, Saswata and Smith, Lois E H and Fu, Zhongjie}
}
@article {1532350,
	title = {Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial and Follow-up Study Results},
	journal = {Ophthalmology},
	volume = {128},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {719-728},
	abstract = {PURPOSE: To evaluate the long-term outcomes of uveitic macular edema (ME). DESIGN: Longitudinal follow-up of a cohort of participants in a randomized clinical trial. PARTICIPANTS: A total of 248 eyes of 177 participants with uveitic ME enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. METHODS: OCT measurements, taken at baseline and annually, were graded by reading center graders masked to clinical data. Macular edema was defined as a center macular thickness (CMT) >=240 μm on time-domain OCT or time-domain OCT equivalent. Resolution of ME was defined as normalization of macular thickness on OCT. Relapse of ME was defined as increase in macular thickness to >=240 μm in an eye that previously had resolution. Visual acuity was measured at each visit with logarithmic visual acuity charts. MAIN OUTCOME MEASURES: Resolution and relapse of ME. Visual acuity. RESULTS: Among 227 eyes with ME followed >=1 year, the cumulative percent of eyes with ME resolving at any point during 7 years was 94\% (95\% confidence interval [CI], 89-97). Epiretinal membranes on OCT were associated with a lower likelihood of ME resolution (hazard ratio [HR], 0.74; 95\% CI, 0.55-1.01; P\&nbsp;= 0.05). Among 177 eyes with resolved ME, the cumulative percent with relapse within 7 years was 43\% (95\% CI, 32-51). Eyes in which ME resolved gained a mean of 6.24 letters (95\% CI, 4.40-8.09; P \&lt; 0.001) compared with eyes that remained free from ME during the 1-year follow-up intervals, whereas eyes in which ME did not resolve experienced no gain in vision (mean change\&nbsp;-1.30 letters; 95\% CI,\&nbsp;-2.70 to 0.09; P\&nbsp;= 0.065), and eyes that developed ME during the year (incident or relapsed) experienced a mean loss of\&nbsp;-8.65 letters (95\% CI,\&nbsp;-11.5 to\&nbsp;-5.84, P\&nbsp;\&lt;\&nbsp;0.001). CONCLUSIONS: Given sufficient time and treatment, nearly all uveitic ME resolves, but episodes of relapse were common. Visual acuity results were better among eyes with resolved ME, suggesting that control of inflammation and resolution of ME might be visually relevant treatment targets.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.08.035},
	author = {Tomkins-Netzer, Oren and Lightman, Susan L and Burke, Alyce E and Sugar, Elizabeth A and Lim, Lyndell L and Jaffe, Glenn J and Altaweel, Michael M and Kempen, John H and Holbrook, Janet T and Jabs, Douglas A and Multicenter Steroid Treatment Trial and Follow-up Study Research Group}
}
@article {988036,
	title = {Vehicle-Controlled, Phase 2 Clinical Trial of a Sustained-Release Dexamethasone Intracanalicular Insert in a Chronic Allergen Challenge Model},
	journal = {J Ocul Pharmacol Ther},
	volume = {33},
	number = {2},
	year = {2017},
	month = {2017 Mar},
	pages = {79-90},
	abstract = {PURPOSE: To evaluate the efficacy and safety of a sustained-release dexamethasone intracanalicular insert (Dextenza{\texttrademark}) in a model of allergic conjunctivitis. METHODS: This was a randomized, double-masked, vehicle-controlled, Phase 2 study. Subjects had to have a positive conjunctival allergen challenge (CAC) reaction to allergen (bilateral +2 itching and redness on 5-point, 0-4 scales) at Visit 1, and for 2 of 3 time points on subsequent visits. Subjects who met entry criteria were randomized to receive Dextenza or PV (vehicle insert). Challenges occurred over 42 days, with efficacy assessed at 14 (primary endpoint visit), 28, and 40 days postinsertion. Outcome measures included the evaluation of ocular itching, redness, tearing, chemosis, eyelid swelling, rhinorrhea, and congestion. RESULTS: Twenty-eight subjects completed the study in the Dextenza group and 31 in the vehicle group. At 14 days postinsertion, Dextenza was statistically superior to PV, with least square mean differences for ocular itching of -0.76, -0.97, and -0.87 at 3, 5, and 7 min post-CAC, and for conjunctival redness of -0.46, -0.66, and -0.68 at 7, 15, and 20 min post-CAC. Clinical significance, defined as a 1-U decrease from PV, was not met for primary efficacy. Secondary endpoints, including number of subjects reporting itching and conjunctival redness, indicated superior performance of Dextenza compared with vehicle. Eleven Dextenza-treated (35.5\%) and 10 vehicle-treated (30.3\%) subjects each experienced a single adverse event. CONCLUSION: This Phase 2 study demonstrated preliminary efficacy and safety data of Dextenza for treatment of allergic conjunctivitis.},
	issn = {1557-7732},
	doi = {10.1089/jop.2016.0154},
	author = {Torkildsen, Gail and Abelson, Mark B and Gomes, Paul J and McLaurin, Eugene and Potts, Susan L and Mah, Francis S}
}
@article {1667693,
	title = {Frontiers in diabetic retinal disease},
	journal = {J Diabetes Complications},
	volume = {37},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {108386},
	abstract = {Diabetic retinal disease (DRD) remains a leading cause of vision loss and blindness globally. Although treatments can be effective when given at vision-threatening stages of DRD, there is a lack of knowledge about the earliest mechanisms leading to the development of clinically evident DRD. Recent advances in retinal imaging methods for patients with diabetes allow a more precise and granular characterization of the different stages of DRD than is provided by the classic Diabetic Retinopathy Severity Scale based on fundus photographs. In addition, recent clinical studies have yielded more information on how to adjust blood glucose levels, lipid levels and blood pressure to minimize the risk of DRD. Given the incomplete success of current therapies, there is a critical need for better understanding of the mechanisms underlying DRD and novel treatment targets that address the entire neurovascular retina. Moreover, the causes for interindividual variability in the development of DRD in patients with similar glycemic history and other metabolic factors are not yet clarified either. Finally, greater focus on patients{\textquoteright} experience with visual disabilities and treatment effects should be addressed in research in this field.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Diagnostic Techniques, Ophthalmological, Humans, Retina, Vision Disorders},
	issn = {1873-460X},
	doi = {10.1016/j.jdiacomp.2022.108386},
	author = {Torm, Marie E Wistrup and Dorweiler, Tim F and Fickweiler, Ward and Levine, S Robert and Fort, Patrice E and Sun, Jennifer K and Gardner, Thomas W}
}
@article {913536,
	title = {Schwannoma of the trochlear nerve-an illustrated case series and a systematic review of management},
	journal = {Neurosurg Rev},
	volume = {41},
	number = {3},
	year = {2018},
	month = {2018 Jul},
	pages = {699-711},
	abstract = {Schwannomas of cranial nerves in the absence of systemic neurofibromatosis are relatively rare. Among these, schwannomas of the trochlear nerve are even less common. They can be found incidentally or when they cause diplopia or other significant neurological deficits. Treatment options include observation only, neuro-ophthalmological intervention, and/or neurosurgical management via resection or sterotactic radiosurgery (SRS). In recent years, the latter has become an attractive therapeutic tool for a number of benign skull base neoplasm including a small number of reports on its successful use for trochlear Schwannomas. However, no treatment algorithm for the management of these tumors has been proposed so far. The goal of this manuscript is to illustrate a case series of this rare entity and to suggest a rational treatment algorithm for trochlear schwannomas, based on our institutional experience of recent cases, and a pertinent review of the literature. Including our series of 5 cases, a total of 85 cases reporting on the management of trochlear schwannomas have been published. Of those reported, less than half (40\&nbsp;\%) of patients underwent surgical resection, whereas the remainder were managed conservatively or with SRS. Seventy-six percent (65/85) of the entire cohort presented with diplopia, which was the solitary symptom in over half of the cases (n\&nbsp;=\&nbsp;39). All patients who presented with symptoms other than diplopia or headaches as solitary symptoms underwent surgical resection. Patients in the non-surgical group were mostly male (M/F\&nbsp;=\&nbsp;3.5:1), presented at an older age and had shorter mean diameter (4.6 vs. 30.4\&nbsp;mm, p\&nbsp;\&lt;\&nbsp;0.0001) when compared to the surgical group. Twelve patients in the entire cohort were treated with SRS, none of whom had undergone surgical resection before or after radiation treatment. Trochlear schwannoma patients without systemic neurofibromatosis are rare and infrequently reported in the literature. Of those, patients harboring symptomatic trochlear Schwannomas do not form a single homogenous group, but fall into two rather distinct subgroups regarding demographics and clinical characteristics. Among those patients in need of intervention, open microsurgical resection as well as less invasive treatment options exist, which all aim at safe relief of symptoms and prevention of progression. Both open microsurgical removal as well as SRS can achieve good long-term local control. Consequently, a tailored multidisciplinary treatment algorithm, based on the individual presentation and tumor configuration, is proposed.},
	issn = {1437-2320},
	doi = {10.1007/s10143-016-0783-y},
	author = {Torun, Nurhan and Laviv, Yosef and Jazi, Kianush Karimian and Mahadevan, Anand and Bhadelia, Rafeeque A and Matthew, Anderson and Strominger, Mitchell and Kasper, Ekkehard M}
}
@article {1328907,
	title = {Oxidative stress induces ferroptotic cell death in retinal pigment epithelial cells},
	journal = {Exp Eye Res},
	volume = {181},
	year = {2019},
	month = {2019 Apr},
	pages = {316-324},
	abstract = {The dysfunction and cell death of retinal pigment epithelial (RPE) cells are hallmarks of late-stage dry (atrophic) age-related macular degeneration (AMD), for which no effective therapy has yet been developed. Previous studies have indicated that iron accumulation is a source of excess free radical production in RPE, and age-dependent iron accumulation in RPE is accelerated in patients with dry AMD. Although the pathogenic role of oxidative stress in RPE in the development of dry AMD is widely accepted, the mechanisms of oxidative stress-induced RPE cell death remain elusive. Here, we show that ferroptotic cell death, a mode of regulated necrosis mediated by iron and lipid peroxidation, is implicated in oxidative stress-induced RPE cell death in vitro. In ARPE-19 cells we observed that the ferroptosis inhibitors ferrostatin-1 and deferoxamine (DFO) rescued tert-butyl hydroperoxide (tBH)-induced RPE cell death more effectively than inhibitors of apoptosis or necroptosis. tBH-induced RPE cell death was accompanied by the three characteristics of ferroptotic cell death: lipid peroxidation, glutathione depletion, and ferrous iron accumulation, which were all significantly attenuated by ferrostatin-1 and DFO. Exogenous iron overload enhanced tBH-induced RPE cell death, but this effect was also attenuated by ferrostatin-1 and DFO. Furthermore, mRNA levels of numerous genes known to regulate iron metabolism were observed to be influenced by oxidative stress. Taken together, our observations suggest that multiple modes of cell death are involved in oxidative stress-induced RPE cell death, with ferroptosis playing a particularly important role.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.08.019},
	author = {Totsuka, Kiyohito and Ueta, Takashi and Uchida, Takatoshi and Roggia, Murilo F and Nakagawa, Suguru and Vavvas, Demetrios G and Honjo, Megumi and Aihara, Makoto}
}
@article {1615204,
	title = {Coming of Age for the Photoreceptor Synapse},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {62},
	number = {12},
	year = {2021},
	month = {2021 Sep 02},
	pages = {24},
	abstract = {Purpose: To discuss the potential contribution of rod and cone synapses to the loss of visual function in retinal injury and disease. Methods: The published literature and the authors{\textquoteright} own work were reviewed. Results: Retinal detachment is used as a case study of rod spherule and cone pedicle plasticity after injury. Both rod and cone photoreceptors terminals are damaged after detachment although the structural changes observed are only partially overlapping. For second-order neurons, only those associated with rod spherules respond consistently to injury by remodeling. Examination of signaling pathways involved in plasticity of conventional synapses and in neural development has been and may continue to be productive in discovering novel therapeutic targets. Rho kinase (ROCK) inhibition is an example of therapy that may reduce synaptic damage by preserving normal synaptic structure of rod and cone cells. Conclusions: We hypothesize that synaptic damage contributes to poor visual restoration after otherwise successful anatomical repair of retinal detachment. A similar situation may exist for patients with degenerative retinal disease. Thus, synaptic structure and function should be routinely studied, as this information may disclose therapeutic strategies to mitigate visual loss.},
	issn = {1552-5783},
	doi = {10.1167/iovs.62.12.24},
	author = {Townes-Anderson, Ellen and Halasz, Eva and Wang, Weiwei and Zarbin, Marco}
}
@article {1664973,
	title = {Asteroid Hyalosis in the National Health and Nutrition Examination Survey 2005 to 2008},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {94-96},
	abstract = {The prevalence of asteroid hyalosis in adults >= 40 years old was 0.6{\textendash}0.8\% in the 2005{\textendash}2008 National Health and Nutrition Examination Survey (NHANES). Older age and elevated serum creatinine were associated with the presence of asteroid hyalosis.},
	keywords = {Humans, Nutrition Surveys, Orbital Diseases, Vision Disorders},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.08.006},
	author = {Tracy, Michaela S and Boland, Michael V and Oke, Isdin}
}
@article {1651379,
	title = {Asteroid Hyalosis in the United States: NHANES 2005-2008},
	journal = {Ophthalmol Retina},
	year = {2022},
	author = {Tracy, M and Boland, MV and Oke, I}
}
@article {1302196,
	title = {Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury},
	journal = {Exp Neurol},
	volume = {300},
	year = {2018},
	month = {2018 Feb},
	pages = {22-29},
	abstract = {The inability of axons to regenerate over long-distances in the central nervous system (CNS) limits the recovery of sensory, motor, and cognitive functions after various CNS injuries and diseases. Although pre-clinical studies have identified a number of manipulations that stimulate some degree of axon growth after CNS damage, the extent of recovery remains quite limited, emphasizing the need for improved therapies. Here, we used traumatic injury to the mouse optic nerve as a model system to test the effects of combining several treatments that have recently been found to promote axon regeneration without the risks associated with manipulating known tumor suppressors or oncogenes. The treatments tested here include TPEN, a chelator of mobile (free) zinc (Zn); shRNA against the axon growth-suppressing transcription factor Klf9; and the atypical growth factor oncomodulin combined with a cAMP analog. Whereas some combinatorial treatments produced only marginally stronger effects than the individual treatments alone, co-treatment with TPEN and Klf9 knockdown had a substantially stronger effect on axon regeneration than either one alone. This combination also promoted a high level of cell survival at longer time points. Thus, Znchelation in combination with Klf9 suppression holds therapeutic potential for promoting axon regeneration after optic nerve injury, and may also be effective for treating other CNS injuries and diseases.},
	issn = {1090-2430},
	doi = {10.1016/j.expneurol.2017.10.025},
	author = {Trakhtenberg, Ephraim F and Li, Yiqing and Feng, Qian and Tso, Janice and Rosenberg, Paul A and Goldberg, Jeffrey L and Benowitz, Larry I}
}
@article {1635631,
	title = {Netarsudil-associated reticular corneal epithelial edema},
	journal = {Am J Ophthalmol Case Rep},
	volume = {25},
	year = {2022},
	month = {2022 Mar},
	pages = {101287},
	abstract = {Purpose: To describe 8 cases of reversible reticular corneal epithelial edema of the cornea that developed after use of the topical Rho-kinase inhibitor netarsudil. Methods: This is a retrospective chart review case series of 8 patients treated with netarsudil at an academic medical center. Observations: Patients had predisposing corneal conditions including penetrating keratoplasty, corneal decompensation after trabeculectomy-associated endophthalmitis, congenital glaucoma with Haab striae, aphakic bullous keratopathy, history of Ahmed valve and silicone oil, and Fuchs endothelial corneal dystrophy undergoing Descemet stripping only. One patient did not have clear predisposing corneal disease other than low endothelial cell density and a history of trabeculectomy. All patients developed reticular corneal epithelial edema, which appeared as collections of moderate sized superficial epithelial bullae arranged in a reticular pattern resembling a honeycomb. Most developed these changes within weeks of initiating netarsudil, but unique to this series are 2 cases in which netarsudil was tolerated by the cornea for months before developing reticular corneal epithelial edema after diode laser cyclophotocoagulation. In cases which underwent anterior segment optical coherence tomography, the imaging demonstrated that the corneal stroma was not edematous, and the reticular corneal epithelial edema involved both host and donor corneal epithelium in cases of penetrating keratoplasty. This fully resolved in all cases upon cessation of netarsudil, and this series is the first to document resolution via a pattern in which the individual bullae become smaller and more widely spaced apart. Conclusion: Netarsudil can cause a reversible reticular corneal epithelial edema.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101287},
	author = {Tran, Jennifer A and Jurkunas, Ula V and Yin, Jia and Davies, Emma C and Sola-Del Valle, David A and Chen, Teresa C and Lin, Michael M}
}
@article {1667697,
	title = {Genetic Associations Between Smoking- and Glaucoma-Related Traits},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {20},
	abstract = {PURPOSE: The purpose of this study was to describe the genetic relationship between smoking and glaucoma. METHODS: We used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants. RESULTS: We identified weak inverse rg between smoking- and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (-0.18 mm Hg per SD, 95\% confidence interval [CI] = -0.30 to -0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95\% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (-0.09 mm Hg per SD, 95\% CI = -0.17 to -0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95\% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P >= 0.38) or OAG (P >= 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P >= 0.13). CONCLUSIONS: MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma. TRANSLATIONAL RELEVANCE: Understanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.},
	keywords = {Glaucoma, Open-Angle, Humans, Intraocular Pressure, Risk Factors, Smoking, Tonometry, Ocular},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.2.20},
	author = {Tran, Jessica H and Stuart, Kelsey V and de Vries, Victor and Vergroesen, Jo{\"e}lle E and Cousins, Clara C and Hysi, Pirro G and Do, Ron and Rocheleau, Ghislain and Kang, Jae H and Wiggs, Janey L and Macgregor, Stuart and Khawaja, Anthony P and Mackey, David A and Klaver, Caroline C W and Ramdas, Wishal D and Pasquale, Louis R and UK Biobank Eye and Vision Consortium, and for the International Glaucoma Genetics Consortium}
}
@article {1364557,
	title = {Advances in Retinal Tissue Engineering},
	journal = {Materials (Basel)},
	volume = {5},
	number = {1},
	year = {2012},
	month = {2012 Jan 05},
	pages = {108-120},
	abstract = {Retinal degenerations cause permanent visual loss and affect millions world-wide. Current treatment strategies, such as gene therapy and anti-angiogenic drugs, merely delay disease progression. Research is underway which aims to regenerate the diseased retina by transplanting a variety of cell types, including embryonic stem cells, fetal cells, progenitor cells and induced pluripotent stem cells. Initial retinal transplantation studies injected stem and progenitor cells into the vitreous or subretinal space with the hope that these donor cells would migrate to the site of retinal degeneration, integrate within the host retina and restore functional vision. Despite promising outcomes, these studies showed that the bolus injection technique gave rise to poorly localized tissue grafts. Subsequently, retinal tissue engineers have drawn upon the success of bone, cartilage and vasculature tissue engineering by employing a polymeric tissue engineering approach. This review will describe the evolution of retinal tissue engineering to date, with particular emphasis on the types of polymers that have routinely been used in recent investigations. Further, this review will show that the field of retinal tissue engineering will require new types of materials and fabrication techniques that optimize the survival, differentiation and delivery of retinal transplant cells.},
	issn = {1996-1944},
	doi = {10.3390/ma5010108},
	author = {Trese, Matthew and Regatieri, Caio V and Young, Michael J}
}
@article {468946,
	title = {Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus.},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {184-8},
	abstract = {BACKGROUND/AIMS: Invasive fungal infections of the head and neck are rare life-threatening infections where prompt diagnosis and intervention is critical for survival. The aim of this study is to determine the clinical characteristics and outcomes of invasive fungal disease of the sinus and orbit, and to compare mucormycosis and Aspergillus infection. METHODS: A retrospective review was conducted from a single tertiary care eye and ear hospital over 20 years (1994-2014). Twenty-four patients with a confirmed pathological diagnosis of invasive fungal disease of the sinus and/or orbit were identified and their medical records were reviewed. The main outcome measures were type of fungus, location of disease, mortality and visual outcome. RESULTS: Patients with orbital involvement had a higher mortality and higher likelihood of mucormycosis infection compared with those with sinus-only disease (78.6\% vs 20\%, p=0.01; 86\% vs 30\%, p=0.01, respectively). Patients with mucormycosis had a higher mortality (71\%) than patients with Aspergillus (29\%); however, this was not statistically significant (p=0.16). All patients with orbital involvement and/or mucormycosis infections were immunosuppressed or had inadequately controlled diabetes, and had a cranial neuropathy or ocular motility dysfunction. All five post-transplant patients with orbital infections died, while the two transplant patients with sinus infections survived. CONCLUSIONS: Patients with orbital fungal infections are more likely to be infected with mucormycosis compared with Aspergillus and have a higher mortality compared with infections sparing the orbit. History of transplant portends a dismal prognosis in orbital infections. Invasive fungal disease should be considered in any immunocompromised patient presenting with a new cranial neuropathy or ocular motility abnormality.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-306945},
	author = {Trief, Danielle and Gray, Stacey T and Jakobiec, Frederick A and Durand, Marlene L and Fay, Aaron and Freitag, Suzanne K and Lee, N Grace and Lefebvre, Daniel R and Holbrook, Eric and Bleier, Benjamin and Sadow, Peter and Rashid, Alia and Chhabra, Nipun and Yoon, Michael K}
}
@article {1559561,
	title = {Widefield Fundus Fluorescein Angiography Features of Uveitis Associated with Juvenile Idiopathic Arthritis},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Dec 02},
	pages = {1-10},
	abstract = {PURPOSE: To evaluate the wide-field fundus fluorescein angiography (WFA) characteristics of uveitis associated with juvenile idiopathic arthritis (JIA-uveitis). METHODS: Retrospective review of records. WFA with Spectralis (Heidelberg) of JIA-uveitis patients were analyzed using the scoring system by Angiography Scoring for Uveitis Nomenclature. RESULTS: Thirty-seven eyes of 20 patients were studied. A total score of at least 1 was noted in 27 eyes (72.97\%). WFA features included optic disc hyperfluorescence (51.35\%), macular leakage (27.03\%), retinal vascular staining/leakage at posterior pole (27.03\%) and peripheral retina (64.86\%), capillary leakage at the posterior pole (37.84\%), and peripheral retina (59.46\%). A decision to change the management plan was made in 8 of 9 patients with bilateral quiet anterior chambers after WFA results. CONCLUSION: More than 70\% of JIA-uveitis eyes showed some WFA-evidence of posterior segment inflammation, which changed the course of therapy for a major proportion of patients with no clinically active anterior chamber inflammation.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1834586},
	author = {Tripathy, Koushik and Ying, Howard and Maldonado Cerda, Anapatricia and Filipowicz, Artur and Kaya, Mahmut and Seymen, Zeynep and Anesi, Stephen D and Chang, Peter Y and Foster, Charles Stephen}
}
@article {1677651,
	title = {In Reply to Elmali and Yazici},
	journal = {Int J Radiat Oncol Biol Phys},
	volume = {115},
	number = {3},
	year = {2023},
	month = {2023 Mar 01},
	pages = {810-811},
	issn = {1879-355X},
	doi = {10.1016/j.ijrobp.2022.10.020},
	author = {Trofimov, Alexei V and Aronow, Mary E and Bussi{\`e}re, Marc R and Gragoudas, Evangelos S and Keane, Florence K and Kim, Ivana K and Shih, Helen A and Bhagwat, Mandar S}
}
@article {1647901,
	title = {A Systematic Comparison of Dose Distributions Delivered in 125I Plaque Brachytherapy and Proton Radiation Therapy for Ocular Melanoma},
	journal = {Int J Radiat Oncol Biol Phys},
	volume = {115},
	number = {2},
	year = {2023},
	month = {2023 Feb 01},
	pages = {501-510},
	abstract = {PURPOSE: To characterize dose distributions with 125I plaque brachytherapy compared with proton radiation therapy for ocular melanoma for relevant clinical scenarios, based on tumor base diameter (d), apical height (h), and location. METHODS AND MATERIALS: Plaque and proton treatment plans were created for 4 groups of cases: (1) REF: 39 instances of reference midsize circular-base tumor (d\&nbsp;=\&nbsp;12 mm, h\&nbsp;=\&nbsp;5 mm), in locations varying by retinal clock hours and distance to fovea, optic disc, and corneal limbus; (2) SUP: 25 superiorly located; (3) TEMP: 25 temporal; and (4) NAS: 25 nasally located tumors that were a fixed distance from the fovea but varying in d (6-18 mm) and h (3-11 mm). For both modalities, 111 unique scenarios were characterized in terms of the distance to points of interest, doses delivered to fovea, optic disc, optic nerve at 3 mm posterior to the disc (ON@3mm), lens, and retina. Comparative statistical evaluation was performed with the Mann-Whitney U test. RESULTS: Superior dose distributions favored plaque for sparing of (1) fovea in large (d\&nbsp;+\&nbsp;h >= 21 mm) NAS tumors; (2) ON@3mm in REF cases located <=4 disc diameters from disc, and in NAS overall. Protons achieved superior dose sparing of (1) fovea and optic disc in REF, SUP, and TEMP; (2) ON@3mm in REF \&gt;4 disc diameters from disc, and in SUP and TEMP; and (3) the lens center overall and lens periphery in REF <=6 mm from the corneal limbus, and in TEMP with h = 3 mm. Although protons could completely spare sections of the retina, plaque dose was more target conformal in the high-dose range (50\% and 90\% of prescription dose). CONCLUSIONS: Although comparison between plaque and proton therapy is not straightforward because of the disparity in dose rate, prescriptions, applicators, and delivery techniques, it is possible to identify distinctions between dose distributions, which could help inform decisions by providers and patients.},
	keywords = {Brachytherapy, Eye Neoplasms, Humans, Melanoma, Proton Therapy, Protons, Radiotherapy Dosage},
	issn = {1879-355X},
	doi = {10.1016/j.ijrobp.2022.07.017},
	author = {Trofimov, Alexei V and Aronow, Mary E and Gragoudas, Evangelos S and Keane, Florence K and Kim, Ivana K and Shih, Helen A and Bhagwat, Mandar S}
}
@article {1417579,
	title = {Ocular adhesives: Design, chemistry, crosslinking mechanisms, and applications},
	journal = {Biomaterials},
	volume = {197},
	year = {2019},
	month = {2019 Mar},
	pages = {345-367},
	abstract = {Closure of ocular wounds after an accident or surgery is typically performed by suturing, which is associated with numerous potential complications, including suture breakage, inflammation, secondary neovascularization, erosion to the surface and secondary infection, and astigmatism; for example, more than half of post-corneal transplant infections are due to suture related complications. Tissue adhesives provide promising substitutes for sutures in ophthalmic surgery. Ocular adhesives are not only intended to address the shortcomings of sutures, but also designed to be easy to use, and can potentially minimize post-operative complications. Herein, recent progress in the design, synthesis, and application of ocular adhesives, along with their advantages, limitations, and potential are discussed. This review covers two main classes of ocular adhesives: (1) synthetic adhesives based on cyanoacrylates, polyethylene glycol (PEG), and other synthetic polymers, and (2) adhesives based on naturally derived polymers, such as proteins and polysaccharides. In addition, different technologies to cover and protect ocular wounds such as contact bandage lenses, contact lenses coupled with novel technologies, and decellularized corneas are discussed. Continued advances in this area can help improve both patient satisfaction and clinical outcomes.},
	issn = {1878-5905},
	doi = {10.1016/j.biomaterials.2019.01.011},
	author = {Trujillo-de Santiago, Grissel and Sharifi, Roholah and Yue, Kan and Sani, Ehsan Shrizaei and Kashaf, Sara Saheb and Alvarez, Mario Mois{\'e}s and Leijten, Jeroen and Khademhosseini, Ali and Dana, Reza and Annabi, Nasim}
}
@article {1351205,
	title = {Novel characterization and live imaging of Schlemm{\textquoteright}s canal expressing Prox-1},
	journal = {PLoS One},
	volume = {9},
	number = {5},
	year = {2014},
	month = {2014},
	pages = {e98245},
	abstract = {Schlemm{\textquoteright}s canal is an important structure of the conventional aqueous humor outflow pathway and is critically involved in regulating the intraocular pressure. In this study, we report a novel finding that prospero homeobox protein 1 (Prox-1), the master control gene for lymphatic development, is expressed in Schlemm{\textquoteright}s canal. Moreover, we provide a novel in vivo method of visualizing Schlemm{\textquoteright}s canal using a transgenic mouse model of Prox-1-green fluorescent protein (GFP). The anatomical location of Prox-1$^{+}$ Schlemm{\textquoteright}s canal was further confirmed by in vivo gonioscopic examination and ex vivo immunohistochemical analysis. Additionally, we show that the Schlemm{\textquoteright}s canal is distinguishable from typical lymphatic vessels by lack of lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expression and absence of apparent sprouting reaction when inflammatory lymphangiogenesis occurred in the cornea. Taken together, our findings offer new insights into Schlemm{\textquoteright}s canal and provide a new experimental model for live imaging of this critical structure to help further our understanding of the aqueous humor outflow. This may lead to new avenues toward the development of novel therapeutic intervention for relevant diseases, most notably glaucoma.},
	keywords = {Animals, Aqueous Humor, Cornea, Gene Expression, Glycoproteins, Gonioscopy, Green Fluorescent Proteins, Homeodomain Proteins, Immunohistochemistry, Intraocular Pressure, Lymphangiogenesis, Lymphatic Vessels, Mice, Mice, Transgenic, Molecular Imaging, Recombinant Fusion Proteins, Sclera, Trabecular Meshwork, Tumor Suppressor Proteins},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0098245},
	author = {Truong, Tan N and Li, Hannah and Hong, Young-Kwon and Chen, Lu}
}
@article {1549014,
	title = {Antibody Testing in Atypical Optic Neuritis},
	journal = {Semin Ophthalmol},
	year = {2020},
	month = {2020 Nov 05},
	pages = {1-9},
	abstract = {Optic neuritis (ON) is a common manifestation of central nervous system demyelinating disorders such as multiple sclerosis (MS). The last two decades have seen increasing recognition of atypical optic neuritis syndromes, driven in large part by characterization of demyelinating diseases associated with antibodies to aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG). Given their increased importance in the workup of ON, familiarity with serological tests for ON has become essential for ophthalmologists. This review will discuss technological aspects, performance, and clinical implications of serological tests for atypical ON.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1820047},
	author = {Truong-Le, Melanie and Chwalisz, Bart}
}
@article {931161,
	title = {Comprehensive Three-Dimensional Analysis of the Neuroretinal Rim in Glaucoma Using High-Density Spectral-Domain Optical Coherence Tomography Volume Scans.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {13},
	year = {2016},
	month = {2016 Oct 1},
	pages = {5498-5508},
	abstract = {Purpose: To describe spectral-domain optical coherence tomography (OCT) methods for quantifying neuroretinal rim tissue in glaucoma and to compare these methods to the traditional retinal nerve fiber layer thickness diagnostic parameter. Methods: Neuroretinal rim parameters derived from three-dimensional (3D) volume scans were compared with the two-dimensional (2D) Spectralis retinal nerve fiber layer (RNFL) thickness scans for diagnostic capability. This study analyzed one eye per patient of 104 glaucoma patients and 58 healthy subjects. The shortest distances between the cup surface and the OCT-based disc margin were automatically calculated to determine the thickness and area of the minimum distance band (MDB) neuroretinal rim parameter. Traditional 150-μm reference surface-based rim parameters (volume, area, and thickness) were also calculated. The diagnostic capabilities of these five parameters were compared with RNFL thickness using the area under the receiver operating characteristic (AUROC) curves. Results: The MDB thickness had significantly higher diagnostic capability than the RNFL thickness in the nasal (0.913 vs. 0.818, P = 0.004) and temporal (0.922 vs. 0.858, P = 0.026) quadrants and the inferonasal (0.950 vs. 0.897, P = 0.011) and superonasal (0.933 vs. 0.868, P = 0.012) sectors. The MDB area and the three neuroretinal rim parameters based on the 150-μm reference surface had diagnostic capabilities similar to RNFL thickness. Conclusions: The 3D MDB thickness had a high diagnostic capability for glaucoma and may be of significant clinical utility. It had higher diagnostic capability than the RNFL thickness in the nasal and temporal quadrants and the inferonasal and superonasal sectors.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-19802},
	author = {Tsikata, Edem and Lee, Ramon and Shieh, Eric and Simavli, Huseyin and Que, Christian J and Guo, Rong and Khoueir, Ziad and de Boer, Johannes and Chen, Teresa C}
}
@article {1043286,
	title = {Automated Brightness and Contrast Adjustment of Color Fundus Photographs for the Grading of Age-Related Macular Degeneration},
	journal = {Transl Vis Sci Technol},
	volume = {6},
	number = {2},
	year = {2017},
	month = {2017 Mar},
	pages = {3},
	abstract = {PURPOSE: The purpose of this study was to develop an algorithm to automatically standardize the brightness, contrast, and color balance of digital color fundus photographs used to grade AMD and to validate this algorithm by determining the effects of the standardization on image quality and disease grading. METHODS: Seven-field color photographs of patients (\&gt;50 years) with any stage of AMD and a control group were acquired at two study sites, with either the Topcon TRC-50DX or Zeiss FF-450 Plus cameras. Field 2 photographs were analyzed. Pixel brightness values in the red, green, and blue (RGB) color channels were adjusted in custom-built software to make the mean brightness and contrast of the images equal to optimal values determined by the Age-Related Eye Disease Study (AREDS) 2 group. RESULTS: Color photographs of 370 eyes were analyzed. We found a wide range of brightness and contrast values in the images at baseline, even for those taken with the same camera. After processing, image brightness variability (brightest image-dimmest image in a color channel) was reduced 69-fold, 62-fold, and 96-fold for the RGB channels. Contrast variability was reduced 6-fold, 8-fold, and 13-fold, respectively, after adjustment. Of the 23\% images considered nongradable before adjustment, only 5.7\% remained nongradable. CONCLUSIONS: This automated software enables rapid and accurate standardization of color photographs for AMD grading. TRANSLATIONAL RELEVANCE: This work offers the potential to be the future of assessing and grading AMD from photos for clinical research and teleimaging.},
	doi = {10.1167/tvst.6.2.3},
	author = {Tsikata, Edem and La{\'\i}ns, In{\^e}s and Gil, Jo{\~a}o and Marques, Marco and Brown, Kelsey and Mesquita, T{\^a}nia and Melo, Pedro and da Luz Cachulo, Maria and Kim, Ivana K and Vavvas, Demetrios and Murta, Joaquim N and Miller, John B and Silva, Rufino and Miller, Joan W and Chen, Teresa C and Husain, Deeba}
}
@article {1179191,
	title = {Volumetric Measurement of Optic Nerve Head Drusen Using Swept-Source Optical Coherence Tomography},
	journal = {J Glaucoma},
	volume = {26},
	number = {9},
	year = {2017},
	month = {2017 Sep},
	pages = {798-804},
	abstract = {PURPOSE: To describe new software tools for quantifying optic nerve head drusen volume using 3-dimensional (3D) swept-source optical coherence tomography (SS-OCT) volumetric scans. MATERIALS AND METHODS: SS-OCT was used to acquire raster volume scans of 8 eyes of 4 patients with bilateral optic nerve head drusen. The scans were manually segmented by 3 graders to identify the drusen borders, and thereafter total drusen volumes were calculated. Linear regression was performed to study the relationships between drusen volume, retinal nerve fiber layer thickness, and Humphrey visual field mean deviation. RESULTS: In the 8 study eyes, drusen volumes ranged between 0.24 to 1.05 mm. Visual field mean deviation decreased by \~{}20 dB per cubic millimeter increase in drusen volume, and the coefficient of correlation of the linear regression was 0.92. In this small patient series, visual field defects were detected when drusen volume was larger than about 0.2 mm. CONCLUSIONS: Software tools have been developed to quantify the size of OHND using SS-OCT volume scans.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000707},
	author = {Tsikata, Edem and Vercellin Verticchio, Alice C and Falkenstein, Iryna and Poon, Linda Yi-Chieh and Brauner, Stacey and Khoueir, Ziad and Miller, John B and Chen, Teresa C}
}
@article {603926,
	title = {Myopic foveoschisis: an ectatic retinopathy, not a schisis.},
	journal = {Eye (Lond)},
	year = {2015},
	month = {2015 Nov 20},
	issn = {1476-5454},
	doi = {10.1038/eye.2015.233},
	author = {Tsilimbaris, M K and Vavvas, D G and Bechrakis, N E}
}
@article {1323944,
	title = {Effects of BNN27, a novel C17-spiroepoxy steroid derivative, on experimental retinal detachment-induced photoreceptor cell death},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Jul 13},
	pages = {10661},
	abstract = {Retinal detachment (RD) leads to photoreceptor cell death secondary to the physical separation of the retina from the underlying retinal pigment epithelium. Intensifying photoreceptor survival in the detached retina could be remarkably favorable for many retinopathies in which RD can be seen. BNN27, a blood-brain barrier (BBB)-permeable, C17-spiroepoxy derivative of dehydroepiandrosterone (DHEA) has shown promising neuroprotective activity through interaction with nerve growth factor receptors, TrkA and p75. Here, we administered BNN27 systemically in a murine model of RD. TUNEL photoreceptors were significantly decreased 24 hours post injury after a single administration of 200 mg/kg BNN27. Furthermore, BNN27 increased inflammatory cell infiltration, as well as, two markers of gliosis 24 hours post RD. However, single or multiple doses of BNN27 were not able to protect the overall survival of photoreceptors 7 days post injury. Additionally, BNN27 did not induce the activation/phosphorylation of TrkA in the detached retina although the mRNA levels of the receptor were increased in the photoreceptors post injury. Together, these findings, do not demonstrate neuroprotective activity of BNN27 in experimentally-induced RD. Further studies are needed in order to elucidate the paradox/contradiction of these results and the mechanism of action of BNN27 in this model of photoreceptor cell damage.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-28633-1},
	author = {Tsoka, Pavlina and Matsumoto, Hidetaka and Maidana, Daniel E and Kataoka, Keiko and Naoumidi, Irene and Gravanis, Achille and Vavvas, Demetrios G and Tsilimbaris, Miltiadis K}
}
@article {1435418,
	title = {NLRP3 inflammasome in NMDA-induced retinal excitotoxicity},
	journal = {Exp Eye Res},
	volume = {181},
	year = {2019},
	month = {2019 Apr},
	pages = {136-144},
	abstract = {N-methyl-D-aspartate (NMDA)-induced excitotoxicity is an acute form of experimental retinal injury as a result of overactivation of glutamate receptors. NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain containing-3) inflammasome, one of the most studied sensors of innate immunity, has been reported to play a critical role in retinal neurodegeneration with controversial implications regarding neuroprotection and cell death. Thus far, it has not been elucidated whether NMDA-mediated excitotoxicity can trigger NLRP3 inflammasome in vivo. Moreover, it is unknown if NLRP3 is beneficial or detrimental to NMDA-mediated retinal cell death. Here, we employed a murine model of NMDA-induced retinal excitotoxicity by administering 100 nmoles of NMDA intravitreally, which resulted in massive TUNEL (TdT-dUTP terminal nick-end labelling) cell death in all retinal layers and especially in retinal ganglion cells (RGCs) 24 h post injection. NMDA insult in the retina potentiates macrophage/microglia cell infiltration, primes the NLRP3 inflammasome in a transcription-dependent manner and induces the expression of interleukin-1β (IL-1β). However, despite NLRP3 inflammasome upregulation, systemic deletion of Nlrp3 or Casp1 (caspase-1) did not significantly alter the NMDA-induced, excitotoxicity-mediated TUNEL retinal cell death at 24 h (acute phase). Similarly, the deletion of the two aforementioned genes did not alter the survival of the Brn3a (brain-specific homeobox/POU domain protein 3A) RGCs in a significant way at 3- or 7-days post injection (long-term phase). Our results indicate that NMDA-mediated retinal excitotoxicity induces immune cell recruitment and NLRP3 inflammasome activity even though inflammasome-mediated neuroinflammation is not a leading contributing factor to cell death in this type of retinal injury.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.01.018},
	author = {Tsoka, Pavlina and Barbisan, Paulo R and Kataoka, Keiko and Chen, Xiaohong Nancy and Tian, Bo and Bouzika, Peggy and Miller, Joan W and Paschalis, Eleftherios I and Vavvas, Demetrios G}
}
@article {1559572,
	title = {Defining Dry Eye from a Clinical Perspective},
	journal = {Int J Mol Sci},
	volume = {21},
	number = {23},
	year = {2020},
	month = {2020 Dec 04},
	abstract = {Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: "Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities." The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.},
	issn = {1422-0067},
	doi = {10.3390/ijms21239271},
	author = {Tsubota, Kazuo and Pflugfelder, Stephen C and Liu, Zuguo and Baudouin, Christophe and Kim, Hyo Myung and Messmer, Elisabeth M and Kruse, Friedrich and Liang, Lingyi and Carreno-Galeano, Jimena Tatiana and Rolando, Maurizio and Yokoi, Norihiko and Kinoshita, Shigeru and Dana, Reza}
}
@article {1263426,
	title = {Distinguishing Benign from Malignant Circumscribed Orbital Tumors in Children},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 16},
	pages = {1-10},
	abstract = {An orbital neoplasm in children is an uncommon clinical finding. Clinical suspicion should be based on many factors, including its location, the nature of onset, associated systemic signs and symptoms, family and social histories, examination findings, and radiographic characteristics. We present two cases of young children of similar age with a rapid-onset orbital mass. In both cases, a circumscribed round lesion was found in the superomedial orbit. An orbital schwannoma, a benign and usually slow growing tumor, was found in the first patient. In contrast, the biopsy of the second patient, who was nearly asymptomatic, revealed a rhabdomyosarcoma. In this review, we have explored the differential diagnosis of relatively common circumscribed round orbital tumors in the pediatric population from both the radiographic (magnetic resonance imaging, MRI) and histopathologic perspectives. A review of highly unusual orbital tumors in children is also provided.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353831},
	author = {Tu, Yufei and Jakobiec, Frederick A and Leung, Katherine and Freitag, Suzanne K}
}
@article {1798431,
	title = {Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection},
	journal = {PLoS One},
	volume = {19},
	number = {1},
	year = {2024},
	month = {2024},
	pages = {e0294526},
	abstract = {PURPOSE: VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing.

DESIGN: Pilot study using ex vivo human eyes.

METHODS: Non-vitrectomized, human eyes from nine donors 75-91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 μL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 μL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 {\textordmasculine}C, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors.

RESULTS: Of the attempted liquid biopsies with the novel 25G VitreoDx, 92\% (66 of 72) resulted in successful acquisition (\&gt;25 μL) while 89\% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25\% of eyes sampled by VitreoDx.

CONCLUSIONS: The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future.},
	keywords = {Biopsy, Feasibility Studies, Humans, Infant, Newborn, Insulins, Intravitreal Injections, Liquid Biopsy, Needles, Pilot Projects, Proteomics, Vitreous Body},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0294526},
	author = {Tumlinson, Alexandre R and Calara, Jennifer M and Azar, Dimitri T and Adamis, Anthony P and Vavvas, Demetrios G and Stewart, Jay M}
}
@article {1016131,
	title = {Outcomes after cataract surgery in eyes with pseudoexfoliation: Results from the Veterans Affairs Ophthalmic Surgery Outcomes Data Project},
	journal = {Can J Ophthalmol},
	volume = {52},
	number = {1},
	year = {2017},
	month = {2017 Feb},
	pages = {61-68},
	abstract = {OBJECTIVE: To compare clinical outcomes of cataract surgery in eyes with and without pseudoexfoliation (PXF). DESIGN: Retrospective deidentified data analysis. PARTICIPANTS: A total of 123 PXF and 4776 non-PXF eyes of patients who underwent cataract surgery. METHODS: We compared data on visual acuity, Visual Function Questionnaire (VFQ)-based quality of life, and complications in PXF and non-PXF eyes from the Veterans Affairs (VA) Ophthalmic Surgery Outcomes Data Project across 5 VA medical centres. RESULTS: Pupillary expansion devices were used in 31 (25.2\%) PXF cases and 398 (8.4\%) non-PXF cases (p \&lt; 0.0001). Capsular tension rings were used in 6 (4.9\%) PXF cases and 55 (1.2\%) non-PXF cases (p \&lt; 0.004). The following complications occurred more frequently in PXF cases: zonular dehiscence without vitrectomy (4 [3.3\%] PXF cases vs 40 [0.8\%] non-PXF cases p = 0.02), persistent inflammation (28 [24.1\%] vs 668 [14.5\%]; p = 0.007), and persistent intraocular pressure elevation (5 [4.3\%] vs 68 [1.5\%]; p = 0.03). Best corrected visual acuity (BCVA) improved in both groups after 1 month, but 87 (83.7\%) PXF cases achieved postoperative BCVA better than or equal to 20/40 compared to 3991 (93.8\%) non-PXF cases (p = 0.0003). There was no significant difference in the postoperative composite VFQ scores between PXF (82.1 {\textpm} 16.9) and non-PXF cases (84.2 {\textpm} 16.8, p = 0.09). CONCLUSIONS: Several complications occurred more frequently in the PXF group compared to the non-PXF group, and fewer PXF cases achieved BCVA better than or equal to 20/40. Despite this, both groups experienced similar improvement in vision-related quality of life after cataract surgery.},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2016.07.019},
	author = {Turalba, Angela and Cakiner-Egilmez, Tulay and Payal, Abhishek R and Gonzalez-Gonzalez, Luis A and Chomsky, Amy S and Vollman, David E and Baze, Elizabeth F and Lawrence, Mary G and Daly, Mary K}
}
@article {503951,
	title = {Cataract Surgery Outcomes in Glaucomatous Eyes: Results From the Veterans Affairs Ophthalmic Surgery Outcomes Data Project.},
	journal = {Am J Ophthalmol},
	volume = {160},
	number = {4},
	year = {2015},
	month = {2015 Oct},
	pages = {693-701.e1},
	abstract = {PURPOSE: To compare visual acuity outcomes, vision-related quality of life, and complications related to cataract surgery in eyes with and without glaucoma. DESIGN: Retrospective cohort study. METHODS: Cataract surgery outcomes in cases with and without glaucoma from the Veterans Affairs Ophthalmic Surgical Outcomes Data Project were compared. RESULTS: We identified 608 glaucoma cases and 4306 controls undergoing planned cataract surgery alone. After adjusting for age, pseudoexfoliation, small pupil, prior ocular surgery, and anterior chamber depth, we found that glaucoma cases were more likely to have posterior capsular tear with vitrectomy (odds ratio [OR] 1.8, P\&nbsp;= .03) and sulcus intraocular lens placement (OR\&nbsp;1.65, P\&nbsp;= .03) during cataract surgery. Glaucoma cases were more likely to have postoperative inflammation (OR 1.73, P \&lt; .0001), prolonged elevated intraocular pressure (OR 2.96, P\&nbsp;= .0003), and additional surgery within 30\&nbsp;days (OR 1.92, P\&nbsp;= .03). Mean best-corrected visual acuity (BCVA) and Visual Function Questionnaire (VFQ) scores significantly improved after cataract surgery in both groups (P \&lt; .0001), but there were larger improvements in BCVA (P\&nbsp;= .01) and VFQ composite scores (P \&lt; .0001) in the nonglaucoma vs the glaucoma group. A total of 3621 nonglaucoma cases (94.1\%) had postoperative BCVA 20/40 or\&nbsp;better, compared to 466 glaucoma cases (89.6\%) (P\&nbsp;= .0003). CONCLUSIONS: Eyes with glaucoma are at increased risk for complications and have more modest visual outcomes after cataract surgery compared to eyes without glaucoma. Despite this, glaucoma patients still experience significant improvement in vision-related outcomes after cataract extraction. Further study is needed to explore potential factors that influence cataract surgery outcomes\&nbsp;in glaucomatous eyes.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.07.020},
	author = {Turalba, Angela and Payal, Abhishek R and Gonzalez-Gonzalez, Luis A and Cakiner-Egilmez, Tulay and Chomsky, Amy S and Vollman, David E and Baze, Elizabeth F and Lawrence, Mary and Daly, Mary K}
}
@article {313131,
	title = {Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide},
	journal = {Clin Ophthalmol},
	volume = {8},
	year = {2014},
	month = {2014},
	pages = {1311-6},
	abstract = {OBJECTIVE: To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. DESIGN: Retrospective comparative case series. PARTICIPANTS: Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. METHODS: A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. MAIN OUTCOME MEASURES: Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. RESULTS: Five out of 19 (26\%) TA cases and 12 out of 23 (52\%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2{\textpm}4.6 in TA cases versus [vs] 14.7{\textpm}5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8{\textpm}1.3 in TA cases vs 1.6{\textpm}1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13\% in the TA group vs 16\% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. CONCLUSIONS: Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S64257},
	author = {Turalba, Angela V and Pasquale, Louis R}
}
@article {1351206,
	title = {Predictors and outcomes of ocular hypertension after open-globe injury},
	journal = {J Glaucoma},
	volume = {23},
	number = {1},
	year = {2014},
	month = {2014 Jan},
	pages = {5-10},
	abstract = {PURPOSE: Evaluate predictors and outcomes of ocular hypertension after open-globe injury. PATIENTS AND METHODS: This is a retrospective, case-control study reviewing records of consecutive patients with open-globe injuries treated at Massachusetts Eye and Ear Infirmary between February 1999 and January 2007. Of 658 patients treated, 382 had at least 2 months of follow-up and sufficient data to be included. Main outcome measures are visual acuity, intraocular pressure (IOP), and type of glaucoma intervention employed. RESULTS: Sixty-five (17\%) patients developed ocular hypertension defined as IOP>=22 mm Hg at \&gt;1 visit or requiring treatment. Increased age (P\&lt;0.001), hyphema (0.025), lens injury (P\&lt;0.0001), and zone II injury (P=0.0254) are risk factors for developing ocular hypertension after open-globe injury. Forty-eight (74\%) patients with ocular hypertension were treated medically, 8 (12\%) underwent filtering or glaucoma drainage device surgery, 5 (8\%) had IOP normalization with observation, while 4 (6\%) required anterior chamber washout with no other glaucoma surgery. Patients with ocular hypertension had an average maximum IOP=33.4 mm Hg at a median follow-up of 21 days, with most patients maintaining normal IOP at all follow-up time points. Visual acuity improved over time with median acuity of hand motions preoperatively, and 20/60 at 12 and 36 months. CONCLUSIONS: Ocular hypertension is a significant complication after open-globe injury that sometimes requires surgical intervention. Predictive factors can alert physicians to monitor for elevated IOP in the first month after trauma. Most patients with traumatic ocular hypertension had improved visual acuity and IOP normalization over time.},
	keywords = {Adult, Age Factors, Case-Control Studies, Corneal Injuries, Eye Injuries, Penetrating, Female, Follow-Up Studies, Humans, Hyphema, Intraocular Pressure, Lens, Crystalline, Male, Middle Aged, Ocular Hypertension, Prognosis, Retrospective Studies, Risk Factors, Sclera, Treatment Outcome, Visual Acuity},
	issn = {1536-481X},
	doi = {10.1097/IJG.0b013e318265bb4a},
	author = {Turalba, Angela V and Shah, Ankoor S and Andreoli, Michael T and Andreoli, Christopher M and Rhee, Douglas J}
}
@article {1452953,
	title = {Dendritic cells mediate the anti-inflammatory action of omega-3 long-chain polyunsaturated fatty acids in experimental autoimmune uveitis},
	journal = {PLoS One},
	volume = {14},
	number = {7},
	year = {2019},
	month = {2019},
	pages = {e0219405},
	abstract = {We previously showed that dietary omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs) suppress inflammation in mice with experimental autoimmune uveitis (EAU). We have now investigated the role of antigen presenting cells (APCs) in this action of ω-3 LCPUFAs. C57BL/6 mice were fed a diet supplemented with ω-3 or ω-6 LCPUFAs for 2 weeks, after which splenocytes were isolated from the mice and cocultured with CD4+ T cells isolated from mice with EAU induced by injection of a human interphotoreceptor retinoid-binding protein peptide together with complete Freund{\textquoteright}s adjuvant. The proliferation of and production of interferon-γ and interleukin-17 by T cells from EAU mice in vitro were attenuated in the presence of splenocytes from ω-3 LCPUFA-fed mice as compared with those from mice fed ω-6 LCPUFAs. Splenocyte fractionation by magnetic-activated cell sorting revealed that, among APCs, dendritic cells (DCs) were the target of ω-3 LCPUFAs. Adoptive transfer of DCs from mice fed ω-3 LCPUFAs attenuated disease progression in EAU mice as well as the production of pro-inflammatory cytokines by T cells isolated from these latter animals. The proliferation of T cells from control Balb/c mice was also attenuated in the presence of DCs from ω-3 LCPUFA-fed mice as compared with those from ω-6 LCPUFA-fed mice. Furthermore, T cell proliferation in such a mixed lymphocyte reaction was inhibited by prior exposure of DCs from mice fed an ω-6 LCPUFA diet to ω-3 LCPUFAs in vitro. Our results thus suggest that DCs mediate the anti-inflammatory action of dietary ω-3 LCPUFAs in EAU.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0219405},
	author = {Uchi, Sho-Hei and Yanai, Ryoji and Kobayashi, Masaaki and Hatano, Makoto and Kobayashi, Yuka and Yamashiro, Chiemi and Nagai, Tomohiko and Kazuo Tokuda and Connor, Kip M and Sonoda, Koh-Hei and Kimura, Kazuhiro}
}
@article {1295881,
	title = {Galectin-3 is an amplifier of the interleukin-1β-mediated inflammatory response in corneal keratinocytes},
	journal = {Immunology},
	volume = {154},
	number = {3},
	year = {2018},
	month = {2018 Jul},
	pages = {490-499},
	abstract = {Interleukin-1β (IL-1β) is a potent mediator of innate immunity commonly up-regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL-1β initiates a signalling cascade that cooperatively induces the expression of canonical IL-1 target genes such as IL-8 and IL-6. Here, we present galectin-3 as a novel regulator of IL-1β responses in corneal keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we show that recombinant exogenous galectin-3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin-3, but not a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, exacerbates the response to IL-1β by stimulating the secretion of inflammatory cytokines. The activity of galectin-3 could be reduced by a novel d-galactopyranoside derivative targeting the conserved galactoside-binding site of galectins and did not involve interaction with IL-1 receptor 1 or the induction of endogenous IL-1β. Consistent with these observations, we demonstrate that small interfering RNA-mediated suppression of endogenous galectin-3 expression is sufficient to impair the IL-1β-induced secretion of IL-8 and IL-6 in a p38 mitogen-activated protein kinase-independent manner. Collectively, our findings provide a novel role for galectin-3 as an amplifier of IL-1β responses during epithelial inflammation through an as yet unidentified mechanism.},
	issn = {1365-2567},
	doi = {10.1111/imm.12899},
	author = {Uchino, Yuichi and Woodward, Ashley M and Mauris, J{\'e}r{\^o}me and Peterson, Kristoffer and Verma, Priya and Nilsson, Ulf J and Rajaiya, Jaya and Arg{\"u}eso, Pablo}
}
@article {1351207,
	title = {Dry eye disease and work productivity loss in visual display users: the Osaka study},
	journal = {Am J Ophthalmol},
	volume = {157},
	number = {2},
	year = {2014},
	month = {2014 Feb},
	pages = {294-300},
	abstract = {PURPOSE: To estimate the impact of dry eye disease (DED) on work performance and productivity in office workers using visual display terminals (VDTs). DESIGN: Cross-sectional study. METHODS: Six hundred seventy-two Japanese young and middle-aged office workers using VDTs completed a questionnaire that was designed to measured at-work performance deficits and productivity losses using the Japanese version of the Work Limitations Questionnaire, completed by e-mail. Using the Japanese dry eye diagnostic criteria, respondents were classified into 3 groups: definite DED, probable DED, and non DED. RESULTS: Of the 672 office workers, 553 subjects (82.3\%), including 366 men and 187 women, completed the questionnaire and underwent clinical evaluation. As for the total workplace productivity loss, the non DED group demonstrated a loss of 3.56\%, those with probable DED demonstrated a loss of 4.06\%, and those with definite DED demonstrated a loss of 4.82\%, indicating significantly worse performance and productivity (P = .014, trend test). For the 4 subscales, DED was associated with significantly lower on-the-job time management (P = .009, trend test) and combined mental performance and interpersonal functioning (P = .011, trend test). After controlling for age, sex, VDT working hours, and diagnosis of DED, time management, physical demands, and mental and interpersonal functioning showed a significant relationship to DED (each P \&gt; .05). Annual DED productivity losses were estimated to be $6160 per employee when measured by total production and $1178 per employee calculated by wage. CONCLUSIONS: This study indicated that there is a significant impact of DED on the total productivity of Japanese VDT users.},
	keywords = {Adult, Aged, Asian Continental Ancestry Group, Computer Terminals, Cross-Sectional Studies, Dry Eye Syndromes, Efficiency, Organizational, Female, Humans, Interpersonal Relations, Japan, Male, Mental Health, Middle Aged, Occupational Diseases, Office Automation, Quality of Life, Sickness Impact Profile, Surveys and Questionnaires, Task Performance and Analysis, Workplace, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.10.014},
	author = {Uchino, Miki and Uchino, Yuichi and Dogru, Murat and Kawashima, Motoko and Yokoi, Norihiko and Komuro, Aoi and Sonomura, Yukiko and Kato, Hiroaki and Kinoshita, Shigeru and Schaumberg, Debra A and Tsubota, Kazuo}
}
@article {382451,
	title = {Alteration of galectin-3 in tears of patients with dry eye disease.},
	journal = {Am J Ophthalmol},
	volume = {159},
	number = {6},
	year = {2015},
	month = {2015 Jun},
	pages = {1027-1035.e3},
	abstract = {PURPOSE: To investigate the expression, release, and proteolytic degradation of galectin-3 in patients with dry eye disease. DESIGN: Observational case series with a comparison group. METHODS: Tear washes and conjunctival impression cytology specimens were collected through standard procedures from 16 patients with dry eye and 11 age-matched healthy subjects. Galectin-3 content in tears was analyzed by quantitative Western blot, using recombinant galectin-3 protein to generate a calibration curve. The relative expression of galectin-3 and matrix metalloproteinase 9 (MMP9) was evaluated by quantitative polymerase chain reaction. The cleavage of galectin-3 was studied in\&nbsp;vitro using activated recombinant MMP9 and protease inhibitors. RESULTS: The concentration of galectin-3 protein in tears, but not galectin-3 expression in conjunctival epithelium, was significantly higher in tears of patients with dry eye (0.38\&nbsp;ng/μg total protein, range 0.04-1.36) compared to healthy subjects (0.12\&nbsp;ng/μg total protein, range 0.00-0.41) (P \&lt; .01). By Western blot, an intact (\~{}28.0\&nbsp;kDa) galectin-3 band was identified in tear samples from healthy subjects, whereas 50\% of the dry eye samples were characterized by the additional presence of a partially degraded form (\~{}25.4\&nbsp;kDa). In our experiments, elevated expression of MMP9 in dry eye subjects correlated with the ability of active MMP9 to cleave galectin-3 from recombinant origin. Interestingly, cleavage of endogenous galectin-3 in tear samples was impaired using a broad-spectrum proteinase inhibitor cocktail, but not the pan-specific MMP inhibitor GM6001, suggesting the presence of proteases other than MMPs in promoting galectin-3 degradation in dry eye. CONCLUSIONS: Our results indicate that release of cellular galectin-3 into tears is associated with epithelial dysfunction in dry eye, and that galectin-3 proteolytic cleavage may contribute to impaired ocular surface barrier function.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2015.02.008},
	author = {Uchino, Yuichi and Mauris, Jerome and Woodward, Ashley M and Dieckow, Julia and Amparo, Francisco and Dana, Reza and Mantelli, Flavio and Arg{\"u}eso, Pablo}
}
@article {742321,
	title = {Impact of Cigarette Smoking on Tear Function and Correlation between Conjunctival Goblet Cells and Tear MUC5AC Concentration in Office Workers.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016},
	pages = {27699},
	abstract = {The first aim of this study was to clarify whether cigarette smoking affects tear secretion, goblet cell density, and tear MUC5AC concentration. The second purpose was to evaluate the correlations of conjunctival goblet cell density with tear MUC5AC concentration and other ocular surface evaluation factors. This cross-sectional study included 88 office workers. All subjects were required to fill in dry eye and smoking questionnaires, in addition to ocular surface evaluation. Tear wash fluid was collected from inferior fornix, and conjunctival epithelium was obtained by impression cytology. Tear MUC5AC concentration was quantified using enzyme-linked immunoassay, and conjunctival goblet cell density was counted after Periodic-acid Schiff staining. Tear MUC5AC concentration had significant positive correlation with conjunctival goblet cell density (r = 0.181, P = 0.03). In current smokers, Schirmer I test value, goblet cell density and tear MUC5AC concentration were significantly lower than non-smokers. Pack-years of smoking have significant negative correlation with goblet cell density (r = -0.174, P = 0.036) and tear MUC5AC concentration (r = -0.183, P = 0.028). We concluded that smoking might decrease tear secretion, goblet cell density and tear MUC5AC concentration. In addition, MUC5AC concentration in tears depends on goblet cell density in the conjunctiva among office workers.},
	issn = {2045-2322},
	doi = {10.1038/srep27699},
	author = {Uchino, Yuichi and Uchino, Miki and Yokoi, Norihiko and Dogru, Murat and Kawashima, Motoko and Komuro, Aoi and Sonomura, Yukiko and Kato, Hiroaki and Argüeso, Pablo and Kinoshita, Shigeru and Tsubota, Kazuo}
}
@article {931166,
	title = {Differential effect of rebamipide on transmembrane mucin biosynthesis in stratified ocular surface epithelial cells.},
	journal = {Exp Eye Res},
	volume = {153},
	year = {2016},
	month = {2016 Dec},
	pages = {1-7},
	abstract = {Mucins are a group of highly glycosylated glycoproteins responsible for the protection of wet-surfaced epithelia. Recent data indicate that transmembrane mucins differ in their contribution to the protective function of the ocular surface, with MUC16 being the most effective barrier on the apical surface glycocalyx. Here, we investigated the role of the mucoprotective drug rebamipide in the regulation of transmembrane mucin biosynthesis using stratified cultures of human corneal and conjunctival epithelial cells. We find that the addition of rebamipide to corneal, but not conjunctival, epithelial cells increased MUC16 protein biosynthesis. Rebamipide did not affect the levels of MUC1, 4 and 20 compared to control. In these experiments, rebamipide had no effect on the expression levels of Notch intracellular domains, suggesting that the rebamipide-induced increase in MUC16 biosynthesis in differentiated corneal cultures is not regulated by Notch signaling. Overall these findings indicate that rebamipide induces the differential upregulation of MUC16 in stratified cultures of human corneal epithelial cells, which may have implications to the proper restoration of barrier function in ocular surface disease.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2016.10.007},
	author = {Uchino, Yuichi and Woodward, Ashley M and Arg{\"u}eso, Pablo}
}
@article {314216,
	title = {Alteration of tear mucin 5AC in office workers using visual display terminals: The Osaka Study},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {8},
	year = {2014},
	month = {2014 Aug},
	pages = {985-92},
	abstract = {IMPORTANCE: There are limited reports on the relationship between mucin 5AC (MUC5AC) concentrations in tears, working hours, and the frequency of ocular symptoms in visual display terminal (VDT) users. This investigation evaluated these relationships among patients with dry eye disease (DED) and individuals serving as controls. OBJECTIVE: To determine the relationship between MUC5AC concentration in the tears of VDT users based on the diagnosis of DED and frequency of ocular symptoms. DESIGN, SETTING, AND PARTICIPANTS: An institutional, cross-sectional study was conducted. Participants included 96 young and middle-aged Japanese office workers. Both eyes of 96 volunteers (60 men and 36 women) were studied. Participants working in a company that used VDTs completed questionnaires about their working hours and the frequency of ocular symptoms. Dry eye disease was diagnosed as definite or probable, or it was not present. Tear fluid was collected from the inferior fornix after instillation of 50 μL of sterilized saline. The MUC5AC concentration was normalized to tear protein content and expressed as MUC5AC (nanograms) per tear protein (milligrams). The differences in MUC5AC concentration between DED groups, between VDT working hours (short, intermediate, and long), and between symptomatic and asymptomatic groups were evaluated with 95\% CIs based on nonparametric Hodges-Lehmann determination. MAIN OUTCOMES AND MEASURES: Ocular surface evaluation, prevalence of DED, and MUC5AC concentration. RESULTS: The prevalence of definite and probable DED was 9\% (n = 9) and 57\% (n = 55), respectively. The mean MUC5AC concentration was lower in the tears of VDT users with definite DED than in those with no DED (P = .02; Hodges-Lehmann estimator, -2.17; 95\% CI, -4.67 to -0.30). The mean MUC5AC concentration in tears was lower in the group that worked longer hours than in the group that worked shorter hours (P = .049; estimated difference, -1.65; 95\% CI, -3.12 to 0.00). Furthermore, MUC5AC concentration was lower in participants with symptomatic eye strain than in asymptomatic individuals (P = .001; estimated difference, -1.71; 95\% CI, -2.86 to -0.63). CONCLUSIONS AND RELEVANCE: The data obtained in the present study suggest that office workers with prolonged VDT use, as well as those with an increased frequency of eye strain, have a low MUC5AC concentration in their tears. Furthermore, MUC5AC concentration in the tears of patients with DED may be lower than that in individuals without DED.},
	keywords = {Adult, Computer Terminals, Cross-Sectional Studies, Dry Eye Syndromes, Female, Humans, Male, Middle Aged, Mucin 5AC, Occupational Diseases, Tears},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.1008},
	author = {Uchino, Yuichi and Uchino, Miki and Yokoi, Norihiko and Dogru, Murat and Kawashima, Motoko and Okada, Naoko and Inaba, Takaaki and Tamaki, Shusaku and Komuro, Aoi and Sonomura, Yukiko and Kato, Hiroaki and Arg{\"u}eso, Pablo and Kinoshita, Shigeru and Tsubota, Kazuo}
}
@article {397881,
	title = {Accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as a research tool for identification of patients with uveitis and scleritis.},
	journal = {Ophthalmic Epidemiol},
	volume = {22},
	number = {2},
	year = {2015},
	month = {2015 Apr},
	pages = {139-41},
	abstract = {PURPOSE: To report on the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying patients with polymyalgia rheumatica (PMR) and concurrent noninfectious inflammatory ocular conditions in a large healthcare organization database. METHODS: Queries for patients with PMR and uveitis or scleritis were executed in two general teaching hospitals{\textquoteright} databases. Patients with ocular infections or other rheumatologic conditions were excluded. Patients with PMR and ocular inflammation were identified, and medical records were reviewed to confirm accuracy. RESULTS: The query identified 10,697 patients with the ICD-9-CM code for PMR and 4154 patients with the codes for noninfectious inflammatory ocular conditions. The number of patients with both PMR and noninfectious uveitis or scleritis by ICD-9-CM codes was 66. On detailed review of the charts of these 66 patients, 31 (47\%) had a clinical diagnosis of PMR, 43 (65\%) had noninfectious uveitis or scleritis, and only 20 (30\%) had PMR with concurrent noninfectious uveitis or scleritis confirmed based on clinical notes. CONCLUSIONS: While the use of ICD-9-CM codes has been validated for medical research of common diseases, our results suggest that ICD-9-CM codes may be of limited value for epidemiological investigations of diseases which can be more difficult to diagnose. The ICD-9-CM codes for rarer diseases (PMR, uveitis and scleritis) did not reflect the true clinical problem in a large proportion of our patients. This is particularly true when coding is performed by physicians outside the area of specialty of the diagnosis.},
	issn = {1744-5086},
	doi = {10.3109/09286586.2015.1012274},
	author = {Uchiyama, Eduardo and Faez, Sepideh and Nasir, Humzah and Unizony, Sebastian H and Plenge, Robert and Papaliodis, George N and Sobrin, Lucia}
}
@article {1615213,
	title = {VEGFR1 signaling in retinal angiogenesis and microinflammation},
	journal = {Prog Retin Eye Res},
	volume = {84},
	year = {2021},
	month = {2021 Sep},
	pages = {100954},
	abstract = {Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, -C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), M{\"u}ller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2021.100954},
	author = {Uemura, Akiyoshi and Fruttiger, Marcus and D{\textquoteright}Amore, Patricia A and De Falco, Sandro and Joussen, Antonia M and Sennlaub, Florian and Brunck, Lynne R and Johnson, Kristian T and Lambrou, George N and Rittenhouse, Kay D and Langmann, Thomas}
}
@article {1474215,
	title = {RIP1 kinase mediates angiogenesis by modulating macrophages in experimental neovascularization},
	journal = {Proc Natl Acad Sci U S A},
	volume = {116},
	number = {47},
	year = {2019},
	month = {2019 Nov 19},
	pages = {23705-23713},
	abstract = {Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in infiltrating macrophages during angiogenesis, and genetic or pharmacological inhibition of RIP1 kinase activity using kinase-inactive RIP1 mice or necrostatin-1 attenuates angiogenesis in laser-induced choroidal neovascularization, Matrigel plug angiogenesis, and alkali injury-induced corneal neovascularization in mice. The inhibitory effect on angiogenesis is mediated by caspase activation through a kinase-independent function of RIP1 and RIP3. Mechanistically, infiltrating macrophages are the key target of RIP1 kinase inhibition to attenuate pathological angiogenesis. Inhibition of RIP1 kinase activity is associated with caspase activation in infiltrating macrophages and decreased expression of proangiogenic M2-like markers but not M1-like markers. Similarly, in vitro, catalytic inhibition of RIP1 down-regulates the expression of M2-like markers in interleukin-4-activated bone marrow-derived macrophages, and this effect is blocked by simultaneous caspase inhibition. Collectively, these results demonstrate a nonnecrotic function of RIP1 kinase activity and suggest that RIP1-mediated modulation of macrophage activation may be a therapeutic target of pathological angiogenesis.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1908355116},
	author = {Ueta, Takashi and Ishihara, Kenji and Notomi, Shoji and Lee, Jong-Jer and Maidana, Daniel E and Efstathiou, Nikolaos E and Murakami, Yusuke and Hasegawa, Eiichi and Azuma, Kunihiro and Toyono, Tetsuya and Paschalis, Eleftherios I and Aihara, Makoto and Miller, Joan W and Vavvas, Demetrios G}
}
@article {1478333,
	title = {Isolated orbital amyloidosis causing internal and external ophthalmoplegia},
	journal = {J AAPOS},
	year = {2019},
	month = {2019 Dec 09},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2019.11.003},
	author = {Ugo Dodd, Mary-Magdalene and Wolkow, Natalie and Cunnane, Mary Elizabeth and Ma, Lina and Dryja, Thaddeus P and Hunter, David}
}
@article {1677821,
	title = {Uveal Melanoma and the IRIS{\textregistered} Registry (Intelligent Research in Sight): A Pilot Analysis and Future Directions},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {284-286},
	keywords = {Humans, Melanoma, Registries, Uveal Neoplasms},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.10.019},
	author = {Uner, Ogul E and Aronow, Mary E and Mruthyunjaya, Prithvi and Materin, Miguel A and Stacey, Andrew W and Wilson, Matthew and Afshar, Armin and Skalet, Alison H}
}
@article {1059841,
	title = {Whole exome sequencing identification of novel candidate genes in patients with proliferative diabetic retinopathy},
	journal = {Vision Res},
	year = {2017},
	month = {2017 May 09},
	abstract = {Rare or novel gene variants in patients with proliferative diabetic retinopathy may contribute to disease development. We performed whole exome sequencing (WES) on patients at the phenotypic extremes of diabetic retinal complications: 57 patients diagnosed with proliferative diabetic retinopathy (PDR) as cases and 13 patients with no diabetic retinopathy despite at least 10years of type 2 diabetes as controls. Thirty-one out of the 57 cases and all 13 controls were from the African American Proliferative Diabetic Retinopathy Study (AA). The rest of the cases were of mixed ethnicities (ME). WES identified 721 candidate genes with rare or novel non-synonymous variants found in at least one case with PDR and not present in any controls. After filtering for genes with null alleles in greater than two cases, 28 candidate genes were identified in our ME cases and 16 genes were identified in our AA cases. Our analysis showed rare and novel variants within these genes that could contribute to the development of PDR, including rare non-synonymous variants in FAM132A, SLC5A9, ZNF600, and TMEM217. We also found previously unidentified variants in VEGFB and APOB. We found that VEGFB, VPS13B, PHF21A, NAT1, ZNF600, PKHD1L1 expression was reduced in human retinal endothelial cells (HRECs) cultured under high glucose conditions. In an exome sequence analysis of patients with PDR, we identified variants in genes that could contribute to pathogenesis. Six of these genes were further validated and found to have reduced expression in HRECs under high glucose conditions, suggestive of an important role in the development of PDR.},
	issn = {1878-5646},
	doi = {10.1016/j.visres.2017.03.007},
	author = {Ung, Cindy and Sanchez, Angie V and Shen, Lishuang and Davoudi, Samaneh and Ahmadi, Tina and Navarro-Gomez, Daniel and Chen, Ching J and Hancock, Heather and Penman, Alan and Hoadley, Suzanne and Consugar, Mark and Restrepo, Carlos and Shah, Vinay A and Arboleda-Velasquez, Joseph F and Sobrin, Lucia and Gai, Xiaowu and Kim, Leo A}
}
@article {1490460,
	title = {Indications, Findings, and Outcomes of Pars Plana Vitrectomy after Open Globe Injury},
	journal = {Ophthalmol Retina},
	volume = {4},
	number = {2},
	year = {2020},
	month = {2020 Feb},
	pages = {216-223},
	abstract = {PURPOSE: To determine the indications, findings, and outcomes of patients with open globe injury (OGI) requiring pars plana vitrectomy (PPV). DESIGN: Retrospective, single-vitreoretinal surgeon case series. PARTICIPANTS: Sixty-one consecutive eyes with OGI that required PPV. METHODS: Retrospective chart review of consecutive patients who underwent PPV after OGI between March 1, 2011, and August 1, 2017, at Massachusetts Eye and Ear by 1 surgeon. MAIN OUTCOME MEASURES: Final visual acuity and rates of recurrent retinal detachment (RD) and proliferative vitreoretinopathy (PVR). RESULTS: Sixty-one eyes of 61 consecutive patients underwent PPV after sustaining OGI. Mean follow-up was 12.8{\textpm}12.1 months (range, 0.5-65 months). At the time of presentation after OGI, 64\% of eyes showed light perception or worse vision. The indications for PPV, which was performed on average of 15 days after injury, included RD without retinal incarceration (39\%), RD with retinal incarceration in the scleral or corneal wound or both (13\%), media opacity without RD (28\%), vitreous traction without RD (11\%), intraocular foreign body (5\%), and endophthalmitis (3\%). At the time of PPV, substantial comorbidities were noted, including corneal trauma (20\%), hyphema (41\%), iris trauma (62\%), lens expulsion (54\%), subretinal hemorrhage (51\%), and choroidal hemorrhage (30\%). Using multivariate analysis, factors associated with RD after initial PPV were preoperative subretinal hemorrhage (odds ratio [OR], 5.73; P\&nbsp;= 0.03), PVR found at initial PPV (OR, 11.94; P\&nbsp;= 0.021), and retinectomy (OR, 17.88; P\&nbsp;= 0.003). No patients were inoperable, because all patients left the operating room with complete retinal reattachment. Of 35 eyes that showed RD, 19 (54\%) redetached as a result of PVR. In 80\% of eyes with RD at initial presentation (28/35 eyes), the retina remained completely attached at last follow-up, and 5 additional eyes remained partially attached (33/35 [94\%]). Of 61 total eyes included in this study, 89\% remained completely attached, and 42 (69\%) achieved visual acuity of 20/200 or better at last follow-up. CONCLUSIONS: Despite substantial ocular comorbidities, PPV can result in retinal reattachment in even the most severe cases. Good visual outcomes can be achieved for most patients who undergo vitreoretinal surgery after open globe trauma.},
	issn = {2468-7219},
	doi = {10.1016/j.oret.2019.09.003},
	author = {Ung, Cindy and Stryjewski, Tomasz P and Eliott, Dean}
}
@article {1478338,
	title = {Infectious corneal ulceration: a proposal for neglected tropical disease status},
	journal = {Bull World Health Organ},
	volume = {97},
	number = {12},
	year = {2019},
	month = {2019 Dec 01},
	pages = {854-856},
	issn = {1564-0604},
	doi = {10.2471/BLT.19.232660},
	author = {Ung, Lawson and Acharya, Nisha R and Agarwal, Tushar and Alfonso, Eduardo C and Bagga, Bhupesh and Bispo, Paulo J M and Burton, Matthew J and Dart, John Kg and Doan, Thuy and Fleiszig, Suzanne Mj and Garg, Prashant and Gilmore, Michael S and Gritz, David C and Hazlett, Linda D and Iovieno, Alfonso and Jhanji, Vishal and Kempen, John H and Lee, Cecilia S and Lietman, Thomas M and Margolis, Todd P and McLeod, Stephen D and Mehta, Jod S and Miller, Darlene and Pearlman, Eric and Prajna, Lalitha and Prajna, N Venkatesh and Seitzman, Gerami D and Shanbhag, Swapna S and Sharma, Namrata and Sharma, Savitri and Srinivasan, Muthiah and Stapleton, Fiona and Tan, Donald Th and Tandon, Radhika and Taylor, Hugh R and Tu, Elmer Y and Tuli, Sonal S and Vajpayee, Rasik B and Van Gelder, Russell N and Watson, Stephanie L and Zegans, Michael E and Chodosh, James}
}
@article {1405417,
	title = {The Persistent Dilemma of Microbial Keratitis: Global Burden, Diagnosis, and Antimicrobial Resistance},
	journal = {Surv Ophthalmol},
	year = {2018},
	month = {2018 Dec 24},
	abstract = {Microbial keratitis (MK) is a potentially blinding condition which must be treated emergently to preserve vision. Although long recognized as a significant cause of corneal blindness, our understanding of its true global scale, associated burden of disease, and etiological patterns remains somewhat limited. Current epidemiological data suggests that MK may be epidemic in parts of the world--particularly within South, South-East and East Asia--and may exceed two million cases per year world-wide. Etiological patterns vary between economically developed and developing countries, with bacterial predominance in the former and fungal predominance in the latter. The key to effective management lies in timely diagnosis; however, the current gold standard of stain and culture remains time consuming and often yields no clinically useful results. For this reason, there are attempts to develop highly sensitive and accurate molecular diagnostic tools to provide rapid diagnosis, inform treatment decision making, and minimize the threat of antimicrobial resistance. We provide an overview of these key areas and of avenues for further research toward the goal of more effectively addressing the problem of MK on both an individual and public health level.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2018.12.003},
	author = {Ung, Lawson and Bispo, Paulo J M and Shanbhag, Swapna S and Gilmore, Michael S and Chodosh, James}
}
@article {1498246,
	title = {Checkpoint inhibitor-induced sarcoid choroidal granulomas},
	journal = {Am J Ophthalmol Case Rep},
	volume = {18},
	year = {2020},
	month = {2020 Jun},
	pages = {100652},
	abstract = {Purpose: To present a novel case of sarcoid choroidal granulomas due to nivolumab therapy for metastatic cutaneous melanoma. Observations: A 55 year-old male with a history of stage III metastatic cutaneous melanoma treated by nivolumab presented with bilateral choroidal lesions. The ophthalmologic examination revealed bilateral creamy, yellow choroidal lesions with no ocular inflammation. The systemic workup revealed pulmonary sarcoidosis confirmed by biopsy. Conclusion: Nivolumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. With the increasing use of immune checkpoint inhibitors in patients with advanced melanoma, clinicians should be aware of this potential associated immune-related adverse event.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2020.100652},
	author = {Ung, Cindy and Gragoudas, Evangelos}
}
@article {1517182,
	title = {Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis},
	journal = {Am J Ophthalmol},
	volume = {214},
	year = {2020},
	month = {2020 06},
	pages = {97-109},
	abstract = {PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: >=1+ anterior chamber cells, >=2\&nbsp;mm infiltrate, or infiltrate <=3\&nbsp;mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n\&nbsp;= 665) and after (Group II, n\&nbsp;= 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0\&nbsp;days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9\% vs Group II, 11.2\%, P\&nbsp;= .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6\% vs 67.7\%, P\&nbsp;= .006), fortified antibiotic prescription (29.7\% vs 53.9\%, P \&lt; .001), and reduction in vision-threatening complications (9.7\% vs 1.8\%, P\&nbsp;= .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4\% vs 5.1\%, P\&nbsp;= .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9\% vs 8.5\%, P \&lt; .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: >=1+ anterior chamber cells (odds ratio [OR] 1.66, 95\% confidence interval 1.09-2.52); >=2\&nbsp;mm infiltrate (OR 4.74, 2.68-8.40); and <=3\&nbsp;mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n\&nbsp;= 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.12.019},
	author = {Ung, Lawson and Wang, Yvonne and Vangel, Mark and Davies, Emma C and Gardiner, Matthew and Bispo, Paulo J M and Gilmore, Michael S and Chodosh, James}
}
@article {1598071,
	title = {Achieving Racial Equity Within Medical Institutions: An Appeal for Action},
	journal = {Mayo Clin Proc},
	volume = {96},
	number = {6},
	year = {2021},
	month = {2021 06},
	pages = {1401-1403},
	keywords = {African Americans, Health Facilities, Health Status Disparities, Healthcare Disparities, Humans, Racism, Schools, Medical, United States},
	issn = {1942-5546},
	doi = {10.1016/j.mayocp.2021.02.031},
	author = {Ung, Lawson and Agarwala, Aalok V and Chodosh, James}
}
@article {1559540,
	title = {COVID-19 and the Unfinished Agenda of VISION 2020},
	journal = {Am J Ophthalmol},
	volume = {224},
	year = {2021},
	month = {2021 04},
	pages = {30-35},
	abstract = {PURPOSE: To critically evaluate the potential impact of the coronavirus disease (COVID-19) pandemic on global ophthalmology and VISION 2020. DESIGN: Perspective supplemented with epidemiologic insights from available online databases. METHODS: We extracted data from the Global Vision Database (2017) and Global Burden of Disease Study (2017) to highlight temporal trends in global blindness since 1990, and provide a narrative overview of how COVID-19 may derail progress toward the goals of VISION 2020. RESULTS: Over 2 decades of VISION 2020 advocacy and program implementation have culminated in a universal reduction of combined age-standardized prevalence of moderate-to-severe vision impairment (MSVI) across all world regions since 1990. Between 1990 and 2017, low-income countries observed large reductions in the age-standardized prevalence per 100,000 persons of vitamin A deficiency (25,155 to 19,187), undercorrected refractive disorders (2,286 to 2,040), cataract (1,846 to 1,690), onchocerciasis (5,577 to 2,871), trachoma (506 to 159), and leprosy (36 to 26). Despite these reductions, crude projections suggest that more than 700 million persons will experience MSVI or blindness by 2050, principally owing to our growing and ageing global population. CONCLUSIONS: Despite the many resounding successes of VISION 2020, the burden of global blindness and vision impairment is set to reach historic levels in the coming years. The impact of COVID-19, while yet to be fully determined, now threatens the hard-fought gains of global ophthalmology. The postpandemic years will require renewed effort and focus on vision advocacy and expanding eye care services worldwide.},
	keywords = {Comorbidity, COVID-19, Eye Diseases, Global Health, Humans, Ophthalmology, Pandemics, SARS-CoV-2, Societies, Medical},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.11.016},
	author = {Ung, Lawson and Jonas, Jost B and Lietman, Thomas M and Chodosh, James}
}
@article {1598049,
	title = {Foundational concepts in the biology of bacterial keratitis},
	journal = {Exp Eye Res},
	year = {2021},
	month = {2021 Jun 04},
	pages = {108647},
	abstract = {Bacterial infections of the cornea, or bacterial keratitis (BK), are notorious for causing rapidly fulminant disease and permanent vision loss, even among treated patients. In the last sixty years, dramatic upward trajectories in the frequency of BK have been observed internationally, driven in large part by the commercialization of hydrogel contact lenses in the late 1960s. Despite this worsening burden of disease, current evidence-based therapies for BK - including broad-spectrum topical antibiotics and, if indicated, topical corticosteroids - fail to salvage vision in a substantial proportion of affected patients. Amid growing concerns of rapidly diminishing antibiotic utility, there has been renewed interest in urgently needed novel treatments that may improve clinical outcomes on an individual and public health level. Bridging the translational gap in the care of BK requires the identification of new therapeutic targets and rational treatment design, but neither of these aims can be achieved without understanding the complex biological processes that determine how bacterial corneal infections arise, progress, and resolve. In this chapter, we synthesize the current wealth of human and animal experimental data that now inform our understanding of basic BK pathophysiology, in context with modern concepts in ocular immunology and microbiology. By identifying the key molecular determinants of clinical disease, we explore how novel treatments can be developed and translated into routine patient care.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2021.108647},
	author = {Ung, Lawson and Chodosh, James}
}
@article {1307447,
	title = {Evaluation of choroidal lesions with swept-source optical coherence tomography},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {88-93},
	abstract = {AIMS: The aim of our study was to image choroidal lesions with swept-source optical coherence tomography (SS-OCT) and to identify the morphological characteristics associated with optimal visualisation. METHODS: This was a prospective, cross-sectional study. Patients with choroidal melanocytic lesions\&nbsp;\&lt;3 mm in thickness on B-scan ultrasonography were recruited. All participants underwent SS-OCT. On SS-OCT we evaluated qualitative (eg, lesion outline, detection of scleral-choroidal interface and quality of the image) and quantitative (measurement of maximum lesion thickness and the largest basal diameter)\&nbsp;parameters. Probability of optimal image quality was examined using ordered logistic regression models. The main outcome measure was quality of the choroidal lesion images on SS-OCT, defined as: optimal, suboptimal or poor. RESULTS: We included 85 choroidal lesions of 82 patients. There were 24 choroidal lesions (29\%) for which image quality was classified as optimal, 31 lesions (37\%) as suboptimal and 30 lesions (36\%) as poor. The factors associated with optimal image quality were distance closer to the fovea (OR 0.76, p\&lt;0.001), posterior pole location (OR 3.87, p=0.05), lower ultrasonography thickness (OR 0.44, p=0.04), lighter lesion pigmentation (OR 0.12, p=0.003) and smaller lesion diameter (OR 0.73, p\&lt;0.001). In the multivariable analysis, closer distance to the fovea (OR 0.81, p=0.005), lighter lesion pigmentation (OR 0.11, p=0.01) and smaller lesion diameter (OR 0.76, p=0.006) remained statistically significant. CONCLUSION: SS-OCT is useful in imaging most choroidal melanocytic lesions. Image quality is best when the choroidal lesion is closer to the fovea, has a smaller diameter and a lighter choroidal pigmentation.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2017-311586},
	author = {Ung, Cindy and La{\'\i}ns, In{\^e}s and Silverman, Rebecca F and Woods, Russell and Lane, Anne Marie and Papakostas, Thanos D and Husain, Deeba and Miller, Joan W and Gragoudas, Evangelos S and Kim, Ivana K and Miller, John B}
}
@article {1608607,
	title = {Urgent unmet needs in the care of bacterial keratitis: An evidence-based synthesis},
	journal = {Ocul Surf},
	year = {2021},
	month = {2021 Aug 28},
	abstract = {Bacterial corneal infections, or bacterial keratitis (BK), are ophthalmic emergencies that frequently lead to irreversible visual impairment. Though increasingly recognized as a major cause of global blindness, modern paradigms of evidence-based care in BK have remained at a diagnostic and therapeutic impasse for over half a century. Current standards of management - based on the collection of corneal cultures and the application of broad-spectrum topical antibiotics - are beset by important yet widely underrecognized limitations, including approximately 30\% of all patients who will develop moderate to severe vision loss in the affected eye. Though recent advances have involved a more clearly defined role for adjunctive topical corticosteroids, and novel therapies such as corneal crosslinking, overall progress to improve patient and population-based outcomes remains incommensurate to the chronic morbidity caused by this disease. Recognizing that the care of BK is guided by the clinical axiom, "time equals vision", this chapter offers an evidence-based synthesis for the clinical management of these infections, underscoring critical unmet needs in disease prevention, diagnosis, and treatment.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2021.08.013},
	author = {Ung, Lawson and Chodosh, James}
}
@article {1445322,
	title = {Intraoperative Optical Coherence Tomography in Vitreoretinal Surgery},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 26},
	pages = {1-6},
	abstract = {Intraoperative OCT (OCT) is an emerging modality capable of displaying real-time OCT images to the surgeon during surgery. The use of iOCT during vitreoretinal surgery improves our understanding of the tissue alterations that occur during surgical manipulations, which may impact surgical decision-making. We review the current OCT modalities and clinical applications of OCT.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620811},
	author = {Ung, Cindy and Miller, John B}
}
@article {1619432,
	title = {"All Labor Has Dignity" - The Case for Wage Equity for Essential Health Care Workers},
	journal = {N Engl J Med},
	volume = {385},
	number = {17},
	year = {2021},
	month = {2021 Oct 21},
	pages = {1539-1542},
	keywords = {Continental Population Groups, Ethnic Groups, Health Personnel, Human rights, Humans, Racism, Respect, Salaries and Fringe Benefits, United States},
	issn = {1533-4406},
	doi = {10.1056/NEJMp2108695},
	author = {Ung, Lawson and Stanford, Fatima Cody and Chodosh, James}
}
@article {1478324,
	title = {The Best of All Worlds: Conjunctivitis through the Lens of Community Ecology and Microbial Biogeography},
	journal = {Microorganisms},
	volume = {8},
	number = {1},
	year = {2019},
	month = {2019 Dec 25},
	abstract = {The study of the forces which govern the geographical distributions of life is known as biogeography, a subject which has fascinated zoologists, botanists and ecologists for centuries. Advances in our understanding of community ecology and biogeography-supported by rapid improvements in next generation sequencing technology-have now made it possible to identify and explain where and why life exists as it does, including within the microbial world. In this review, we highlight how a unified model of microbial biogeography, one which incorporates the classic ecological principles of selection, diversification, dispersion and ecological drift, can be used to explain community dynamics in the settings of both health and disease. These concepts operate on a multiplicity of temporal and spatial scales, and together form a powerful lens through which to study microbial population structures even at the finest anatomical resolutions. When applied specifically to curious strains of conjunctivitis-causing, nonencapsulated , we show how this conceptual framework can be used to explain the possible evolutionary and disease-causing mechanisms which allowed these lineages to colonize and invade a separate biogeography. An intimate knowledge of this radical bifurcation in phylogeny, still the only known niche subspecialization for to date, is critical to understanding the pathogenesis of ocular surface infections, nature of host-pathogen interactions, and developing strategies to curb disease transmission.},
	issn = {2076-2607},
	doi = {10.3390/microorganisms8010046},
	author = {Ung, Lawson and Bispo, Paulo J M and Bryan, Noelle C and Andre, Camille and Chodosh, James and Gilmore, Michael S}
}
@article {1439866,
	title = {Pharmacological Induction of a Progenitor State for the Efficient Expansion of Primary Human Hepatocytes},
	journal = {Hepatology},
	volume = {69},
	number = {5},
	year = {2019},
	month = {2019 May},
	pages = {2214-2231},
	abstract = {The liver is an organ with strong regenerative capacity, yet primary hepatocytes have a low amplification potential in vitro, a major limitation for the cell-based therapy of liver disorders and for ex vivo biological screens. Induced pluripotent stem cells (iPSCs) may help to circumvent this obstacle but often harbor genetic and epigenetic abnormalities, limiting their potential. Here, we describe the pharmacological induction of proliferative human hepatic progenitor cells (HPCs) through a cocktail of growth factors and small molecules mimicking the signaling events involved in liver regeneration. Human HPCs from healthy donors and pediatric patients proliferated vigorously while maintaining their genomic stability and could be redifferentiated in vitro into metabolically competent cells that supported the replication of hepatitis B and delta viruses. Redifferentiation efficiency was boosted by three-dimensional culture. Finally, transcriptome analysis showed that HPCs were more closely related to mature hepatocytes than iPSC-derived hepatocyte-like cells were. Conclusion: HPC induction holds promise for a variety of applications such as ex vivo disease modeling, personalized drug testing or metabolic studies, and development of a bioartificial liver.},
	issn = {1527-3350},
	doi = {10.1002/hep.30425},
	author = {Unzu, Carmen and Planet, Evarist and Brandenberg, Nathalie and Fusil, Floriane and Cassano, Marco and Perez-Vargas, Jimena and Friedli, Marc and Cosset, Fran{\c c}ois-Lo{\"\i}c and Lutolf, Matthias P and Wildhaber, Barbara E and Trono, Didier}
}
@article {369026,
	title = {The role of conjunctival biopsy in the diagnosis of granulomatosis with polyangiitis.},
	journal = {J Ophthalmic Inflamm Infect},
	volume = {5},
	number = {1},
	year = {2015},
	month = {2015 Dec},
	pages = {1},
	abstract = {BACKGROUND: The purpose of this study is to describe a patient who was diagnosed with granulomatosis with polyangiitis based on conjunctival biopsy. This study is a case report and review of the literature. FINDINGS: A 48-year-old Caucasian woman presented with a 2-week history of a left eye peripheral corneal ulcer with adjacent conjunctivitis and a 4-month history of a non-resolving productive cough. Given her elevated serum perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as a chest computed topography (CT) that showed bilateral patchy infiltrates, suspicion of limited granulomatosis with polyangiitis with lung and ocular involvement was high. Because bronchoalveolar lavage was nondiagnostic for granulomatous disease, conjunctival biopsy was initially attempted in order to avoid a more invasive lung biopsy. The conjunctival biopsy revealed mixed subacute inflammatory mediators and vasculitis consistent with granulomatosis with polyangiitis. CONCLUSIONS: Conjunctival biopsy may be a valuable, minimally invasive method for diagnosing systemic granulomatosis with polyangiitis.},
	issn = {1869-5760},
	doi = {10.1186/s12348-014-0033-9},
	author = {Ursea, Roxana and De Castro, Dawn and Bowen, Trent J and Chan, Chi-Chao}
}
@article {680446,
	title = {Storage Temperature Alters the Expression of Differentiation-Related Genes in Cultured Oral Keratinocytes.},
	journal = {PLoS One},
	volume = {11},
	number = {3},
	year = {2016},
	month = {2016},
	pages = {e0152526},
	abstract = {PURPOSE: Storage of cultured human oral keratinocytes (HOK) allows for transportation of cultured transplants to eye clinics worldwide. In a previous study, one-week storage of cultured HOK was found to be superior with regard to viability and morphology at 12{\textdegree}C compared to 4{\textdegree}C and 37{\textdegree}C. To understand more of how storage temperature affects cell phenotype, gene expression of HOK before and after storage at 4{\textdegree}C, 12{\textdegree}C, and 37{\textdegree}C was assessed.

MATERIALS AND METHODS: Cultured HOK were stored in HEPES- and sodium bicarbonate-buffered Minimum Essential Medium at 4{\textdegree}C, 12{\textdegree}C, and 37{\textdegree}C for one week. Total RNA was isolated and the gene expression profile was determined using DNA microarrays and analyzed with Partek Genomics Suite software and Ingenuity Pathway Analysis. Differentially expressed genes (fold change > 1.5 and P < 0.05) were identified by one-way ANOVA. Key genes were validated using qPCR.

RESULTS: Gene expression of cultures stored at 4{\textdegree}C and 12{\textdegree}C clustered close to the unstored control cultures. Cultures stored at 37{\textdegree}C displayed substantial change in gene expression compared to the other groups. In comparison with 12{\textdegree}C, 2,981 genes were differentially expressed at 37{\textdegree}C. In contrast, only 67 genes were differentially expressed between the unstored control and the cells stored at 12{\textdegree}C. The 12{\textdegree}C and 37{\textdegree}C culture groups differed most significantly with regard to the expression of differentiation markers. The Hedgehog signaling pathway was significantly downregulated at 37{\textdegree}C compared to 12{\textdegree}C.

CONCLUSION: HOK cultures stored at 37{\textdegree}C showed considerably larger changes in gene expression compared to unstored cells than cultured HOK stored at 4{\textdegree}C and 12{\textdegree}C. The changes observed at 37{\textdegree}C consisted of differentiation of the cells towards a squamous epithelium-specific phenotype. Storing cultured ocular surface transplants at 37{\textdegree}C is therefore not recommended. This is particularly interesting as 37{\textdegree}C is the standard incubation temperature used for cell culture.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0152526},
	author = {Utheim, Tor Paaske and Islam, Rakibul and Fostad, Ida G and Eidet, Jon R and Sehic, Amer and Olstad, Ole K and Dartt, Darlene A. and Messelt, Edward B and Griffith, May and Pasovic, Lara}
}
@article {382636,
	title = {Serum-free and xenobiotic-free preservation of cultured human limbal epithelial cells.},
	journal = {PLoS One},
	volume = {10},
	number = {3},
	year = {2015},
	month = {2015},
	pages = {e0118517},
	abstract = {AIM/PURPOSE OF THE STUDY: To develop a one-week storage method, without serum and xenobiotics, that would maintain cell viability, morphology, and phenotype of cultured human limbal epithelial sheets. MATERIALS AND METHODS: Human limbal explants were cultured on intact human amniotic membranes for two weeks. The sheets were stored in a hermetically sealed container at 23{\textdegree}C in either a serum-free medium with selected animal serum-derived compounds (Quantum 286) or a xenobiotic-free medium (Minimal Essential Medium) for 4 and 7 days. Stored and non-stored cultures were analyzed for cell viability, amniotic membrane and epithelial sheet thickness, and a panel of immunohistochemical markers for immature cells (ΔNp63α, p63, Bmi-1, C/EBP∂, ABCG2 and K19), differentiated cells (K3 and Cx43), proliferation (PCNA), and apoptosis (Caspase-3). RESULTS: The cell viability of the cultures was 98 {\textpm} 1\% and remained high after storage. Mean central thickness of non-stored limbal epithelial sheets was 23 {\textpm} 3 μm, and no substantial loss of cells was observed after storage. The non-stored epithelial sheets expressed a predominantly immature phenotype with ΔNp63α positivity of more than 3\% in 9 of 13 cultures. After storage, the expression of ABCG2 and C/EBP∂ was reduced for the 7 day Quantum 286-storage group; (P = 0.04), and Bmi-1 was reduced after 4 day Quantum 286-storage; (P = 0.02). No other markers varied significantly. The expression of differentiation markers was unrelated to the thickness of the epithelia and amniotic membrane, apart from ABCG2, which correlated negatively with thickness of limbal epithelia (R = -0.69, P = 0.01) and ΔNp63α, which correlated negatively with amniotic membrane thickness (R = -0.59, P = 0.03). CONCLUSION: Limbal epithelial cells cultured from explants on amniotic membrane can be stored at 23{\textdegree}C in both serum-free and xenobiotic-free media, with sustained cell viability, ultrastructure, and ΔNp63α-positivity after both 4 and 7 days.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0118517},
	author = {Utheim, Oeygunn and Islam, Rakibul and Lyberg, Torstein and Roald, Borghild and Eidet, Jon Roger and de la Paz, Maria Fideliz and Dartt, Darlene A. and Raeder, Sten and Utheim, Tor Paaske}
}
@article {1430542,
	title = {Effects of explant size on epithelial outgrowth, thickness, stratification, ultrastructure and phenotype of cultured limbal epithelial cells},
	journal = {PLoS One},
	volume = {14},
	number = {3},
	year = {2019},
	month = {2019},
	pages = {e0212524},
	abstract = {PURPOSE: Transplantation of limbal stem cells is a promising therapy for limbal stem cell deficiency. Limbal cells can be harvested from either a healthy part of the patient{\textquoteright}s eye or the eye of a donor. Small explants are less likely to inflict injury to the donor site. We investigated the effects of limbal explant size on multiple characteristics known to be important for transplant function. METHODS: Human limbal epithelial cells were expanded from large versus small explants (3 versus 1 mm of the corneal circumference) for 3 weeks and characterized by light microscopy, immunohistochemistry, and transmission electron microscopy. Epithelial thickness, stratification, outgrowth, ultrastructure and phenotype were assessed. RESULTS: Epithelial thickness and stratification were similar between the groups. Outgrowth size correlated positively with explant size (r = 0.37; P = 0.01), whereas fold growth correlated negatively with explant size (r = -0.55; P \&lt; 0.0001). Percentage of cells expressing the limbal epithelial cell marker K19 was higher in cells derived from large explants (99.1{\textpm}1.2\%) compared to cells derived from small explants (93.2{\textpm}13.6\%, P = 0.024). The percentage of cells expressing ABCG2, integrin β1, p63, and p63α that are markers suggestive of an immature phenotype; Keratin 3, Connexin 43, and E-Cadherin that are markers of differentiation; and Ki67 and PCNA that indicate cell proliferation were equal in both groups. Desmosome and hemidesmosome densities were equal between the groups. CONCLUSION: For donor- and culture conditions used in the present study, large explants are preferable to small in terms of outgrowth area. As regards limbal epithelial cell thickness, stratification, mechanical strength, and the attainment of a predominantly immature phenotype, both large and small explants are sufficient.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0212524},
	author = {Utheim, O A and Pasovic, L and Raeder, S and Eidet, J R and Fostad, I G and Sehic, A and Roald, B and de la Paz, M F and Lyberg, T and Dartt, D A and Utheim, T P}
}
@article {1323945,
	title = {Effect of Transportation on Cultured Limbal Epithelial Sheets for Worldwide Treatment of Limbal Stem Cell Deficiency},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	month = {2018 Jul 12},
	pages = {10502},
	abstract = {Limbal stem cell deficiency can be treated with transplantation of cultured human limbal epithelial cells (LEC). It can be advantageous to produce LEC in centralized labs and thereafter ship them to eye clinics. The present study used transport simulations of LEC to determine if vigorous shaking during transport altered the viability, morphology and phenotype during a 4 day-long storage of LEC with a previously described serum-free storage method. Inserts with LEC cultured on amniotic membranes were sutured to caps inside air-tight containers with generous amounts of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES)-buffered minimal essential medium (MEM). The containers were distributed among the following testing conditions: 6 hours with full containers, 36 hours with full containers, 36 hours with container three quarters full of medium, and 36 hours with container full of medium containing a shear-protecting agent (Pluronic-F68). Compared to stored, but non-transported controls, no statistically significant changes in viability and immunohistochemical staining were observed. The epithelial sheets remained intact. However, an air-liquid interface in the containers reduced the number of desmosomes and hemi-desmosomes compared to the controls. In conclusion, cultured LEC sheets appear to endure vigorous shaking for at least 36 hours if the container is full.},
	issn = {2045-2322},
	doi = {10.1038/s41598-018-28553-0},
	author = {Utheim, O A and Lyberg, T and Eidet, J R and Raeder, S and Sehic, A and Roald, B and Messelt, E and de la Paz, M F and Dartt, D A and Utheim, T P}
}
@article {1302184,
	title = {Visual search for changes in scenes creates long-term, incidental memory traces},
	journal = {Atten Percept Psychophys},
	volume = {80},
	number = {4},
	year = {2018},
	month = {2018 May},
	pages = {829-843},
	abstract = {Humans are very good at remembering large numbers of scenes over substantial periods of time. But how good are they at remembering changes to scenes? In this study, we tested scene memory and change detection two weeks after initial scene learning. In Experiments 1-3, scenes were learned incidentally during visual search for change. In Experiment 4, observers explicitly memorized scenes. At test, after two weeks observers were asked to discriminate old from new scenes, to recall a change that they had detected in the study phase, or to detect a newly introduced change in the memorization experiment. Next, they performed a change detection task, usually looking for the same change as in the study period. Scene recognition memory was found to be similar in all experiments, regardless of the study task. In Experiment 1, more difficult change detection produced better scene memory. Experiments 2 and 3 supported a "depth-of-processing" account for the effects of initial search and change detection on incidental memory for scenes. Of most interest, change detection was faster during the test phase than during the study phase, even when the observer had no explicit memory of having found that change previously. This result was replicated in two of our three change detection experiments. We conclude that scenes can be encoded incidentally as well as explicitly and that changes in those scenes can leave measurable traces even if they are not explicitly recalled.},
	issn = {1943-393X},
	doi = {10.3758/s13414-018-1486-y},
	author = {Utochkin, Igor S and Wolfe, Jeremy M}
}
@article {1661598,
	title = {Surgical goniolens for tag identification and removal in DMEK surgery},
	journal = {Eur J Ophthalmol},
	volume = {33},
	number = {3},
	year = {2023},
	month = {2023 May},
	pages = {1480-1483},
	abstract = {INTRODUCTION: We describe a novel technique for identifying endothelial Descemet membrane (DM) tags remaining after descemetorhexis in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) surgery. METHODS: A surgical goniolens is applied to the corneal surface after descemetorhexis in order to visualize the peripheral inner corneal layer at 360{\textdegree} and identify endothelial-DM tags. RESULTS: A detailed visualization of the peripheral inner corneal layer is possible using goniolens, without using any staining in the anterior chamber. CONCLUSION: The technique may be used to screen the posterior corneal surface for any retained endothelial-DM tags. It may to lower the risk of remaining tags and indirectly lower the incidence of DMEK graft detachment.},
	keywords = {Cornea, Corneal Diseases, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies, Visual Acuity},
	issn = {1724-6016},
	doi = {10.1177/11206721221149482},
	author = {Vaccaro, Sabrina and Bosio, Lorenzo and Parekh, Mohit and Gadhvi, Kunal A and Giannaccare, Giuseppe and Scorcia, Vincenzo and Semeraro, Francesco and Kaye, Stephen B and Romano, Vito}
}
@article {1351208,
	title = {Risk of glaucoma after early bilateral oophorectomy},
	journal = {Menopause},
	volume = {21},
	number = {4},
	year = {2014},
	month = {2014 Apr},
	pages = {391-8},
	abstract = {OBJECTIVE: Because early estrogen deficiency may increase the susceptibility of the optic nerve to glaucoma, we studied the association of early bilateral oophorectomy with glaucoma. METHODS: In the Mayo Clinic Cohort Study of Oophorectomy and Aging, we studied the risk of glaucoma by comparing women who underwent bilateral oophorectomy from 1950 to 1987 with age-matched referent women who did not undergo unilateral or bilateral oophorectomy. Glaucoma diagnostic codes were identified in the records linkage system of the Rochester Epidemiology Project. Hazard ratios (HRs) were calculated during a median follow-up of 25.5 years. Analyses were stratified by age at the time of bilateral oophorectomy (in tertiles). RESULTS: Of 1,044 women who underwent bilateral oophorectomy before menopause, 147 developed glaucoma. Of 1,070 referent women, 133 developed glaucoma. Women who underwent bilateral oophorectomy showed no increased risk of glaucoma in the overall group (HR, 1.12; 95\% CI, 0.89-1.42). However, women who underwent oophorectomy before the age of 43 years (n = 344; first tertile) had a significantly increased risk of glaucoma (HR, 1.60; 95\% CI, 1.15-2.23). The results did not change after adjustment for hypertension, obesity, diabetes, or disorders of lipid metabolism at baseline. Approximately 11\% of women who had undergone bilateral oophorectomy before the age of 43 years were treated with estrogen up to the age of 50 years; however, treatment did not reduce the association (HR, 1.59; 95\% CI, 0.81-3.13). CONCLUSIONS: Bilateral oophorectomy before the age of 43 years may increase the risk of glaucoma, and estrogen treatment does not seem to attenuate the risk.},
	keywords = {Adult, Age Factors, Aging, Cohort Studies, Estrogen Replacement Therapy, Estrogens, Female, Glaucoma, Humans, Middle Aged, Ovariectomy, Proportional Hazards Models, Risk Factors},
	issn = {1530-0374},
	doi = {10.1097/GME.0b013e31829fd081},
	author = {Vajaranant, Thasarat S and Grossardt, Brandon R and Maki, Pauline M and Pasquale, Louis R and Sit, Arthur J and Shuster, Lynne T and Rocca, Walter A}
}
@article {1328908,
	title = {Racial Differences in the Effects of Hormone Therapy on Incident Open-Angle Glaucoma in a Randomized Trial},
	journal = {Am J Ophthalmol},
	volume = {195},
	year = {2018},
	month = {2018 Nov},
	pages = {110-120},
	abstract = {PURPOSE: We conducted a secondary analysis of a randomized, placebo-controlled trial to test if hormone therapy (HT) altered the risk of open-angle glaucoma (OAG), and if the risk reduction varied by race. DESIGN: Secondary analysis of randomized controlled trial data. METHODS: We linked Medicare claims data to 25 535 women in the Women{\textquoteright}s Health Initiative. Women without a uterus were randomized to receive either oral conjugated equine estrogens (CEE 0.625\&nbsp;mg/day) or placebo, and women with a uterus received oral CEE and medroxyprogesterone acetate (CEE 0.625\&nbsp;mg/day\&nbsp;+ MPA 2.5\&nbsp;mg/day) or placebo. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95\% confidence interval. RESULTS: After exclusion of women with prevalent glaucoma or without claims for eye care provider visits, the final analysis included 8102 women (mean age\&nbsp;= 68.5 {\textpm} 4.8 years). The OAG incidence was 7.6\% (mean follow-up\&nbsp;= 11.5 {\textpm} 5.2 years; mean HT duration\&nbsp;= 4.4 {\textpm} 2.3 years). Increased age (P trend\&nbsp;= .01) and African-American race (HR\&nbsp;= 2.69, 95\% CI\&nbsp;= 2.13-3.42; white as a reference) were significant risk factors for incident OAG. We found no overall benefit of HT in reducing incident OAG (HR\&nbsp;= 1.01, 95\% CI\&nbsp;= 0.79-1.29 in the CEE trial, and HR\&nbsp;= 1.05, 95\% CI\&nbsp;= 0.85-1.29 in the CEE\&nbsp;+ MPA trial). However, race modified the relationship between CEE use and OAG risk (P interaction\&nbsp;= .01), and risk was reduced in African-American women treated with CEE (HR\&nbsp;= 0.49, 95\% CI\&nbsp;= 0.27-0.88), compared to placebo. Race did not modify the relation between CEE\&nbsp;+ MPA use and OAG risk (P interaction\&nbsp;= .68). CONCLUSIONS: Analysis suggests that HT containing estrogen, but not a combination of estrogen and progesterone, reduces the risk of incident OAG among African-American women. Further investigation is needed.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.07.035},
	author = {Vajaranant, Thasarat Sutabutr and Ray, Roberta M and Pasquale, Louis R and Mares, Julie A and Ritch, Robert and Gower, Emily W and Haan, Mary N and Jackson, Rebecca D and Maki, Pauline M}
}
@article {1761836,
	title = {A novel approach to hypophysitis: outcomes using non-glucocorticoid immunosuppressive therapy},
	journal = {Eur J Endocrinol},
	volume = {189},
	number = {3},
	year = {2023},
	month = {2023 Sep 01},
	pages = {309-317},
	abstract = {OBJECTIVE: To determine pituitary function before and after nonglucocorticoid immunosuppressive therapy (NGIT) in subjects with hypophysitis and evaluate their clinical and radiologic outcomes. DESIGN: Retrospective, longitudinal study. METHODS: We reviewed a large database, selected subjects with hypophysitis treated with NGIT, and collected information on the duration of therapy, and clinical, hormonal, and radiologic outcomes. RESULTS: Twelve subjects met the inclusion criteria. Five subjects had primary hypophysitis (PH), while seven had secondary hypophysitis (SH) due to an underlying systemic inflammatory disease. Mean age {\textpm} SD was 48.0 {\textpm} 15.7 years and 40.9 {\textpm} 13.0 years, for PH and SH, respectively. The majority were female (PH 60\% and SH 86\%). BMI {\textpm} SD at presentation was 25.2 {\textpm} 2.5 kg/m2 and 26.8 {\textpm} 6.7 kg/m2 for PH and SH, respectively. The most common symptom at presentation was fatigue (75\%). All PH subjects (100\%) and 2 (28.6\%) SH subjects had polyuria/polydipsia. There was a significant decrease in mean pituitary stalk thickness after NGIT (P = .0051) (mean duration 16.5 {\textpm} 4.8 months). New hormone loss or recovery occurred rarely. Mycophenolate mofetil was the most used NGIT: adverse effects prompted discontinuation in 2 out of 7 subjects. CONCLUSIONS: Subjects with hypophysitis receiving NGIT had stable or improved brain/pituitary magnetic resonance imaging findings with a significant decrease in pituitary stalk thickness. NGITs did not improve anterior pituitary function. Our findings suggest that NGIT may be considered as an alternative therapy for patients with hypophysitis who require immunosuppression.},
	keywords = {Female, Humans, Hypophysitis, Immunosuppression Therapy, Immunosuppressive Agents, Longitudinal Studies, Male, Retrospective Studies},
	issn = {1479-683X},
	doi = {10.1093/ejendo/lvad115},
	author = {Vakharia, Janaki D and Muhammed, Maged and Remba-Shapiro, Ilan and Marsiglia, Marcela and Hadaway, Natalia and Chwalisz, Bart K and Nachtigall, Lisa B}
}
@article {1677621,
	title = {Macular Neovascularization in Choroideremia},
	journal = {Ophthalmol Retina},
	volume = {7},
	number = {7},
	year = {2023},
	month = {2023 Jul},
	pages = {604},
	keywords = {Choroideremia, Humans, Neovascularization, Pathologic, Tomography, Optical Coherence},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2023.02.013},
	author = {Valastro, Antonio and Romano, Francesco and Salvetti, Anna Paola}
}
@article {1517179,
	title = {Uveitis Therapy: The Corticosteroid Options},
	journal = {Drugs},
	volume = {80},
	number = {8},
	year = {2020},
	month = {2020 Jun},
	pages = {765-773},
	abstract = {Uveitis is characterized by intraocular inflammation involving the uveal tract; its etiologies generally fall into two broad categories: autoimmune/inflammatory or infectious. Corticosteroids \&nbsp;are a powerful and important class of medications ubiquitous in the treatment of uveitis. They may be given systemically or locally, in the form of topical drops, periocular injection, intravitreal suspension, or intravitreal implant. This review describes each of the currently available corticosteroid treatment options for uveitis, including favorable and unfavorable characteristics of each as well as applicable clinical trials. The main advantage of corticosteroids as a whole is their ability to quickly and effectively control inflammation early on in the course of uveitis. However, they can have serious side effects, whether localized to the eye (such as cataract and elevated intraocular pressure) or systemic (such as osteonecrosis and adrenal insufficiency) and in the majority of cases of uveitis are not an appropriate option for long-term therapy.},
	issn = {1179-1950},
	doi = {10.1007/s40265-020-01314-y},
	author = {Valdes, Lianna M and Sobrin, Lucia}
}
@article {1653603,
	title = {Anti-infliximab antibodies and clinical response in noninfectious uveitis and scleritis patients treated with infliximab: A retrospective review},
	journal = {Am J Ophthalmol Case Rep},
	volume = {27},
	year = {2022},
	month = {2022 Sep},
	pages = {101634},
	abstract = {Purpose: To investigate the clinical response to infliximab in ocular inflammation patients who develop anti-infliximab antibodies (AIA) vs. those patients who do not develop AIA. Observations: A retrospective review was performed of patients treated with infliximab for noninfectious uveitis (NIU) or scleritis. Clinical response was determined as a composite clinical endpoint and classified as complete, partial, or absent. Nine of 32 infliximab-treated patients (28\%) were found to develop AIA. Among the AIA-positive patients, clinical response was complete in 7 patients (78\%) and partial in 2 patients (22\%). Among the AIA-negative patients, clinical response was complete in 15 patients (65\%), partial in 6 patients (26\%) and absent in 2 patients (9\%). Serum infliximab levels tended to decrease with appearance of AIA but rarely became undetectable. Conclusions and Importance: In this pilot study, AIA-positive patients did not have diminished clinical response to infliximab when compared with AIA-negative patients. There was a high rate of complete clinical response to infliximab in this group of NIU and scleritis patients. Approximately a quarter of patients developed AIA. AIA-positive patients did not have diminished rates of clinical response when compared with AIA-negative patients. This suggests that routine AIA monitoring may not be clinically useful, although validation of this finding in larger cohorts is necessary.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2022.101634},
	author = {Valdes, Lianna and Cox, Jacob T and Yang, Janine and Susarla, Gayatri and Han, Samuel and Papaliodis, George N and Sobrin, Lucia}
}
@article {1538343,
	title = {Application of Metagenomic Sequencing in the Diagnosis of Infectious Uveitis},
	journal = {Semin Ophthalmol},
	year = {2020},
	month = {2020 Oct 18},
	pages = {1-4},
	abstract = {: to summarize the origin and very recent history of the use of metagenomic sequencing for the diagnosis of infectious uveitis, convey the technique as described by one of the primary institutions experimenting with the technology, and present recent successful applications of the technology as well as potential advantages and pitfalls compared to other current diagnostic tools.: review of peer-reviewed literature concerning metagenomic sequencing for the diagnosis of infectious uveitis.: compared to existing diagnostic methods, metagenomic deep sequencing is a sensitive, unbiased, and comprehensive technique with great potential for diagnosing the causative pathogens of cases of infectious uveitis. However, many issues remain to be addressed in the process of developing this technology, including but not limited to the potentially overwhelming amount of information generated,\&nbsp;definition of diagnostic thresholds, demonstration of validity, contamination, and cost.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1818795},
	author = {Valdes, Lianna and Bispo, Paulo and Sobrin, Lucia}
}
@article {303936,
	title = {Retinal microangiopathy in a mouse model of inducible mural cell loss},
	journal = {Am J Pathol},
	volume = {184},
	number = {10},
	year = {2014},
	month = {2014 Oct},
	pages = {2618-26},
	abstract = {Diabetes can lead to vision loss because of progressive degeneration of the neurovascular unit in the retina, a condition known as diabetic retinopathy. In its early stages, the pathology is characterized by microangiopathies, including microaneurysms, microhemorrhages, and nerve layer infarcts known as cotton-wool spots. Analyses of postmortem human retinal tissue and retinas from animal models indicate that degeneration of the pericytes, which constitute the outer layer of capillaries, is an early event in diabetic retinopathy; however, the relative contribution of specific cellular components to the pathobiology of diabetic retinopathy remains to be defined. We investigated the phenotypic consequences of pericyte death on retinal microvascular integrity by using nondiabetic mice conditionally expressing a diphtheria toxin receptor in mural cells. Five days after administering diphtheria toxin in these adult mice, changes were observed in the retinal vasculature that were similar to those observed in diabetes, including microaneurysms and increased vascular permeability, suggesting that pericyte cell loss is sufficient to trigger retinal microvascular degeneration. Therapies aimed at preventing or delaying pericyte dropout may avoid or attenuate the retinal microangiopathy associated with diabetes.},
	keywords = {Animals, Capillaries, Diabetic Retinopathy, Disease Models, Animal, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microvessels, Pericytes, Retina, Retinal Degeneration, Retinal Vessels},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2014.06.011},
	author = {Valdez, Cammi N and Arboleda-Velasquez, Joseph F and Amarnani, Dhanesh S and Kim, Leo A and D{\textquoteright}Amore, Patricia A}
}
@article {341741,
	title = {Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits and belong to a distinct phylogenetic cluster.},
	journal = {Nat Commun},
	volume = {5},
	year = {2014},
	month = {2014},
	pages = {5411},
	abstract = {Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes respiratory and invasive infections as well as conjunctivitis. Strains that lack the capsule, a main virulence factor and the target of current vaccines, are often isolated from conjunctivitis cases. Here we perform a comparative genomic analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal codes in the United States. We find that the vast majority of conjunctivitis strains are members of a distinct cluster of closely related unencapsulated strains. These strains possess divergent forms of pneumococcal virulence factors (such as CbpA and neuraminidases) that are not shared with other unencapsulated nasopharyngeal S. pneumoniae. They also possess putative adhesins that have not been described in encapsulated pneumococci. These findings suggest that the unencapsulated strains capable of causing conjunctivitis utilize a pathogenesis strategy substantially different from that described for S. pneumoniae at other infection sites.},
	issn = {2041-1723},
	doi = {10.1038/ncomms6411},
	author = {Valentino, Michael D and McGuire, Abigail Manson and Rosch, Jason W and Bispo, Paulo J M and Burnham, Corinna and Sanfilippo, Christine M and Carter, Robert A and Zegans, Michael E and Beall, Bernard and Earl, Ashlee M and Tuomanen, Elaine I and Morris, Timothy W and Haas, Wolfgang and Gilmore, Michael S}
}
@article {280921,
	title = {Friend turned foe: evolution of enterococcal virulence and antibiotic resistance},
	journal = {Annu Rev Microbiol},
	volume = {68},
	year = {2014},
	month = {2014},
	pages = {337-56},
	abstract = {The enterococci are an ancient genus that evolved along with the tree of life. These intrinsically rugged bacteria are highly adapted members of the intestinal consortia of a range of hosts that spans the animal kingdom. Enterococci are also leading opportunistic hospital pathogens, causing infections that are often resistant to treatment with most antibiotics. Despite the importance of enterococci as hospital pathogens, the vast majority live outside of humans, and nearly all of their evolutionary history took place before the appearance of modern humans. Because hospital infections represent evolutionary end points, traits that exacerbate human infection are unlikely to have evolved for that purpose. However, clusters of traits have converged in specific lineages that are well adapted to colonize the antibiotic-perturbed gastrointestinal tracts of patients and that thrive in the hospital environment. Here we discuss these traits in an evolutionary context, as well as how comparative genomics is providing new insights into the evolution of the enterococci.},
	keywords = {Animals, Anti-Bacterial Agents, Biological Evolution, Drug Resistance, Bacterial, Enterococcus, Gram-Positive Bacterial Infections, Humans, Virulence},
	issn = {1545-3251},
	doi = {10.1146/annurev-micro-091213-113003},
	author = {Van Tyne, Daria and Gilmore, Michael S}
}
@article {913541,
	title = {Novel Phagocytosis-Resistant Extended-Spectrum β-Lactamase-Producing Escherichia coli From Keratitis.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {11},
	year = {2016},
	month = {2016 Nov 01},
	pages = {1306-1309},
	abstract = {Importance: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are highly antibiotic resistant, and primary ocular infection by ESBL E coli has rarely been reported. A novel mutation conferring phagocytosis resistance would position a strain well to infect the cornea. Observations: A woman with recurrent keratitis presented with a corneal ulcer, which was culture positive for ESBL E coli. Resistant to nearly all other antimicrobials, the infection was treated with amikacin and polymyxin B-trimethoprim, and the ulcer resolved over 3 weeks. Analysis of the E coli genome showed it to belong to multilocus sequence type 131 (ST131). This isolate was found to possess a novel deletion in yrfF, an essential regulator of bacterial capsule synthesis. Disruption of yrfF, which confers mucoidy and increased virulence, has not been previously observed in ESBL E coli from any infection site. This novel variant was experimentally proven to cause the mucoid phenotype, and corresponding resistance to phagocytic killing. Conclusions and Relevance: Increased resistance to immune clearance in an ESBL E coli lineage already known for its virulence is an unsettling development. This phenotype, which likely positioned it as an unusual cause of corneal ulcer, can be easily recognized in the laboratory, which should help limit its spread.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.3283},
	author = {Van Tyne, Daria and Ciolino, Joseph B and Wang, Jay and Durand, Marlene L and Gilmore, Michael S}
}
@article {1016136,
	title = {Raising the Alarmone: Within-Host Evolution of Antibiotic-Tolerant Enterococcus faecium},
	journal = {MBio},
	volume = {8},
	number = {1},
	year = {2017},
	month = {2017 Feb 21},
	abstract = {Enterococci are ancient commensal bacteria that recently emerged as leading causes of antibiotic-resistant, hospital-acquired infection. Vancomycin-resistant enterococci (VRE) epitomize why drug-resistant enterococcal infections are a problem: VRE readily colonize the antibiotic-perturbed gastrointestinal (GI) tract where they amplify to large numbers, and from there, they infect other body sites, including the bloodstream, urinary tract, and surgical wounds. VRE are resistant to many antimicrobials and host defenses, which facilitates establishment at the site of infection and confounds therapeutic clearance. Having evolved to colonize the GI tract, VRE are comparatively ill adapted to the human bloodstream. A recent study by Honsa and colleagues (E. S. Honsa et al., mBio 8:e02124-16, 2017, https://doi.org/10.1128/mBio.02124-16) found that a strain of vancomycin-resistant Enterococcus\&nbsp;faecium evolved antibiotic tolerance within the bloodstream of an immunocompromised host by activating the stringent response through mutation of relA Precisely how VRE colonize and infect and the selective pressures that led to the outgrowth of relA mutants are the subjects of ongoing research.},
	issn = {2150-7511},
	doi = {10.1128/mBio.00066-17},
	author = {Van Tyne, Daria and Gilmore, Michael S}
}
@article {303861,
	title = {A delicate balance: maintaining mutualism to prevent disease.},
	journal = {Cell Host Microbe},
	volume = {16},
	number = {4},
	year = {2014},
	month = {2014 Oct 8},
	pages = {425-7},
	abstract = {The intestinal microbial ecosystem is complex, and few of the principles that contribute to homeostasis in health are well understood. Pham et\&nbsp;al. (2014) show that a network including the epithelial interleukin-22 receptor protects against infection with the opportunistic pathogen Enterococcus faecalis through promotion of host-microbiota mutualism.},
	issn = {1934-6069},
	doi = {10.1016/j.chom.2014.09.019},
	author = {Van Tyne, Daria and Gilmore, Michael S}
}
@article {1363214,
	title = {Structure, function, and biology of the Enterococcus faecalis cytolysin},
	journal = {Toxins (Basel)},
	volume = {5},
	number = {5},
	year = {2013},
	month = {2013 Apr 29},
	pages = {895-911},
	abstract = {Enterococcus faecalis is a Gram-positive commensal member of the gut microbiota of a wide range of organisms. With the advent of antibiotic therapy, it has emerged as a multidrug resistant, hospital-acquired pathogen. Highly virulent strains of E. faecalis express a pore-forming exotoxin, called cytolysin, which lyses both bacterial and eukaryotic cells in response to quorum signals. Originally described in the 1930s, the cytolysin is a member of a large class of lanthionine-containing bacteriocins produced by Gram-positive bacteria. While the cytolysin shares some core features with other lantibiotics, it possesses unique characteristics as well. The current understanding of cytolysin biosynthesis, structure/function relationships, and contribution to the biology of E. faecalis are reviewed, and opportunities for using emerging technologies to advance this understanding are discussed.},
	keywords = {Animals, Bacteriocins, Cross Infection, Enterococcus faecalis, Gram-Positive Bacterial Infections, Humans, Molecular Structure},
	issn = {2072-6651},
	doi = {10.3390/toxins5050895},
	author = {Van Tyne, Daria and Martin, Melissa J and Gilmore, Michael S}
}
@article {1435419,
	title = {Impact of antibiotic treatment and host innate immune pressure on enterococcal adaptation in the human bloodstream},
	journal = {Sci Transl Med},
	volume = {11},
	number = {487},
	year = {2019},
	month = {2019 Apr 10},
	abstract = {Multidrug-resistant enterococcal strains emerged in the early 1980s and are now among the leading causes of drug-resistant bacterial infection worldwide. We used functional genomics to study an early bacterial outbreak in patients in a Wisconsin hospital between 1984 and 1988 that was caused by multidrug-resistant The goal was to determine how a clonal lineage of became adapted to growth and survival in the human bloodstream. Genome sequence analysis revealed a progression of increasingly fixed mutations and repeated independent occurrences of mutations in a relatively small set of genes. Repeated independent mutations suggested selection within the host during the course of infection in response to pressures such as host immunity and antibiotic treatment. We observed repeated independent mutations in a small number of loci, including a little studied polysaccharide utilization pathway and the locus. Functional studies showed that mutating these loci rendered better able to withstand antibiotic pressure and innate immune defenses in the human bloodstream. We also observed a shift in mutation pattern that corresponded to the introduction of carbapenem antibiotics in 1987. This work identifies pathways that allow enterococci to survive the transition from the human gut into the bloodstream, enabling them to cause severe bacteremia associated with high mortality.},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.aat8418},
	author = {Van Tyne, Daria and Manson, Abigail L and Huycke, Mark M and Karanicolas, John and Earl, Ashlee M and Gilmore, Michael S}
}
@article {1435420,
	title = {AAV Engineering Identifies a Species Barrier That Highlights a Portal to the Brain},
	journal = {Mol Ther},
	volume = {27},
	number = {5},
	year = {2019},
	month = {2019 May 08},
	pages = {901-903},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2019.04.006},
	author = {Vandenberghe, Luk H}
}
@article {1511498,
	title = {COVID-19: Gene Transfer to the Rescue?},
	journal = {Hum Gene Ther},
	volume = {31},
	number = {11-12},
	year = {2020},
	month = {2020 06},
	pages = {605-607},
	keywords = {Animals, Antibodies, Neutralizing, Clinical Trials as Topic, Coronavirus Infections, Gene Transfer Techniques, Humans, Technology Transfer, Translational Medical Research, Viral Vaccines},
	issn = {1557-7422},
	doi = {10.1089/hum.2020.29125.lhv},
	author = {Vandenberghe, Luk H}
}
@article {416971,
	title = {What Is Next for Retinal Gene Therapy?},
	journal = {Cold Spring Harb Perspect Med},
	year = {2015},
	month = {2015 Apr 15},
	abstract = {The field of gene therapy for retinal blinding disorders is experiencing incredible momentum, justified by hopeful results in early stage clinical trials for inherited retinal degenerations. The premise of the use of the gene as a drug has come a long way, and may have found its niche in the treatment of retinal disease. Indeed, with only limited treatment options available for retinal indications, gene therapy has been proven feasible, safe, and effective and may lead to durable effects following a single injection. Here, we aim at putting into context the promise and potential, the technical, clinical, and economic boundaries limiting its application and development, and speculate on a future in which gene therapy is an integral component of ophthalmic clinical care.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a017442},
	author = {Vandenberghe, Luk H}
}
@article {1363215,
	title = {Predictability of intraocular lens power calculation formulae in infantile eyes with unilateral congenital cataract: results from the Infant Aphakia Treatment Study},
	journal = {Am J Ophthalmol},
	volume = {156},
	number = {6},
	year = {2013},
	month = {2013 Dec},
	pages = {1252-1260.e2},
	abstract = {PURPOSE: To compare accuracy of intraocular lens (IOL) power calculation formulae in infantile eyes with primary IOL implantation. DESIGN: Comparative case series. METHODS: The Hoffer Q, Holladay 1, Holladay 2, Sanders-Retzlaff-Kraff (SRK) II, and Sanders-Retzlaff-Kraff theoretic (SRK/T) formulae were used to calculate predicted postoperative refraction for eyes that received primary IOL implantation in the Infant Aphakia Treatment Study. The protocol targeted postoperative hyperopia of\&nbsp;+6.0 or\&nbsp;+8.0 diopters (D). Eyes were excluded for invalid biometry, lack of refractive data at the specified postoperative visit, diagnosis of glaucoma or suspected glaucoma, or sulcus IOL placement. Actual refraction 1\&nbsp;month after surgery was converted to spherical equivalent and prediction error (predicted refraction\&nbsp;- actual refraction) was calculated. Baseline characteristics were analyzed for effect on prediction error for each formula. The main outcome measure was absolute prediction error. RESULTS: Forty-three eyes were studied; mean axial length was 18.1 {\textpm} 1.1\&nbsp;mm (in 23 eyes, it was \&lt;18.0\&nbsp;mm). Average age at surgery was 2.5 {\textpm} 1.5\&nbsp;months. Holladay 1 showed the lowest median absolute prediction error (1.2 D); a paired comparison of medians showed clinically similar results using the Holladay 1 and SRK/T formulae (median difference, 0.3 D). Comparison of the mean absolute prediction error showed the lowest values using the SRK/T formula (1.4 {\textpm} 1.1 D), followed by the Holladay 1 formula (1.7 {\textpm} 1.3 D). Calculations with an optimized constant showed the lowest values and no significant difference between the Holladay 1 and SRK/T formulae (median difference, 0.3 D). Eyes with globe AL of less than 18\&nbsp;mm had the largest mean and median prediction error and absolute prediction error, regardless of the formula used. CONCLUSIONS: The Holladay 1 and SRK/T formulae gave equally good results and had the best predictive value for infant eyes.},
	keywords = {Aphakia, Postcataract, Biometry, Cataract, Cataract Extraction, Humans, Infant, Lens Implantation, Intraocular, Lenses, Intraocular, Optics and Photonics, Refraction, Ocular, Reproducibility of Results, Treatment Outcome, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.07.014},
	author = {VanderVeen, Deborah K and Trivedi, Rupal H and Nizam, Azhar and Lynn, Michael J and Lambert, Scott R and Infant Aphakia Treatment Study Group}
}
@article {1532373,
	title = {Outcomes of Secondary Intraocular Lens Implantation in the Infant Aphakia Treatment Study},
	journal = {J Cataract Refract Surg},
	year = {2020},
	month = {2020 Sep 07},
	abstract = {PURPOSE: To report outcomes of secondary intraocular lens (IOL) implantation in the Infant Aphakia Treatment Study (IATS) SETTING:: Multicenter clinical practice DESIGN:: Secondary analysis of patients enrolled in a randomized clinical trial METHODS:: Details regarding all secondary IOL surgeries conducted in children enrolled in the IATS were compiled. We evaluated visual outcomes, refractive outcomes, and adverse events at age 10 {\textonehalf} years. Comparisons were made to eyes that remained aphakic and to eyes randomized to primary IOL placement. RESULTS: 55/57 patients randomized to aphakia with contact lens correction were seen for the 10 {\textonehalf} year study visit; 24/55 eyes (44\%) had secondary IOL surgery. Median age at IOL surgery was 5.4 years (range 1.7 to 10.3 years). Mean absolute prediction error was 1.0 {\textpm} 0.7D. At age 10 {\textonehalf} years, the median log MAR VA was 0.9 (range 0.2 to 1.7), similar to VA in the 31 eyes still aphakic (0.8, range 0.1 to 2.9); the number of eyes with stable or improved VA scores between the 4 {\textonehalf} and 10 {\textonehalf} year study visits was also similar (78\% secondary IOL eyes, 84\% aphakic eyes). For eyes undergoing IOL implantation after the 4.5 year study visit (n=22), the mean refraction at age 10 {\textonehalf} years was -3.2 {\textpm}2.7D (range -9.9D to 1.1D), compared to -5.5 {\textpm}6.6 D (n=53, range -26.5 to 3.0D) in eyes with primary IOL (p=0.03). CONCLUSIONS: Delayed IOL implantation allows a more predictable refractive outcome at age 10 {\textonehalf} years, though the range of refractive error is still large.},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000000412},
	author = {VanderVeen, Deborah K and Drews-Botsch, Carolyn D and Nizam, Azhar and Bothun, Erick D and Wilson, Lorri B and Wilson, M Edward and Lambert, Scott R and Infant Aphakia Treatment Study}
}
@article {1043291,
	title = {Anti-Vascular Endothelial Growth Factor Therapy for Primary Treatment of Type 1 Retinopathy of Prematurity: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {124},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {619-633},
	abstract = {
	PURPOSE: To review the available evidence on the ocular safety and efficacy of anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) compared with laser photocoagulation therapy. METHODS: A literature search of the PubMed and Cochrane Library databases was conducted last on September 6, 2016, with no date restrictions and limited to articles published in English. This search yielded 311 citations, of which 37 were deemed clinically relevant for full-text review. Thirteen of these were selected for inclusion in this assessment. The panel methodologist assigned ratings to the selected articles according to the level of evidence. RESULTS: Of the 13 citations, 6 articles on 5 randomized clinical trials provided level II evidence supporting the use of anti-VEGF agents, either as monotherapy or in combination with laser therapy. The primary outcome for these articles included recurrence of ROP and the need for retreatment (3 articles), retinal structure (2 articles), and refractive outcome (1 article). Seven articles were comparative case series that provided level III evidence. The primary outcomes included the effects of anti-VEGF treatment on development of peripheral retinal vessels (1\&nbsp;article), refractive outcomes (1 article), or both structural and refractive or visual outcomes (5 articles). CONCLUSIONS: Current level II and III evidence indicates that intravitreal anti-VEGF therapy is as effective as laser photocoagulation for achieving regression of acute ROP. Although there are distinct ocular advantages to anti-VEGF pharmacotherapy for some cases (such as eyes with zone I disease or aggressive posterior ROP), the disadvantages are that the ROP recurrence rate is higher, and vigilant and extended follow-up is needed because retinal vascularization is usually incomplete. After intravitreal injection, bevacizumab can be detected in serum within 1 day, and serum VEGF levels are suppressed for at least 8 to 12 weeks. The effects of lowering systemic VEGF levels on the developing organ systems of premature infants are unknown, and there are limited long-term data on potential systemic and neurodevelopmental effects after anti-VEGF use for ROP treatment. Anti-VEGF agents should be used judiciously and with awareness of the known and unknown or potential side effects.

},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.12.025},
	author = {VanderVeen, Deborah K and Melia, Michele and Yang, Michael B and Hutchinson, Amy K and Wilson, Lorri B and Lambert, Scott R}
}
@article {669286,
	title = {Strabismus at Age 2 Years in Children Born Before 28 Weeks{\textquoteright} Gestation: Antecedents and Correlates.},
	journal = {J Child Neurol},
	volume = {31},
	number = {4},
	year = {2016},
	month = {2016 Mar},
	pages = {451-60},
	abstract = {Children born very preterm are at greater risk of ophthalmic morbidities, including strabismus, than children born at term. We evaluated perinatal factors associated with strabismus at age 2 years in a large population of infants delivered before 28 weeks{\textquoteright} gestation. A total of 996 infants in the multicenter ELGAN (Extremely Low Gestational Age Newborn) study who had a retinal exam in infancy and a developmental assessment at 2 years corrected age are included. Their mothers were interviewed about the pregnancy, and both mother and newborn charts were reviewed. Certified examiners administered the Bayley Scales of Infant Development-II and performed an examination of ocular alignment. Time-oriented logistic regression risk models were created to evaluate the associations of characteristics and exposures with the development of strabismus. Overall, 14\% (n = 141) of the children had strabismus at 2 years, and 80\% of strabismic children had esotropia. Characteristics associated with strabismus were birth before 26 weeks{\textquoteright} gestation, severe fetal growth restriction, and maternal history of aspirin ingestion. Associated postnatal factors included a SNAP-II (Score for Neonatal Acute Physiology) illness severity value >=30, brain ventriculomegaly, type I retinopathy of prematurity, and ventilator-dependent severe bronchopulmonary dysplasia. Strabismus in very preterm populations is associated with a number of antenatal and postnatal antecedents as well as clinical and imaging correlates indicative of brain damage in these children. Routine ophthalmologic assessments in the early years can allow appropriate and timely interventions.},
	issn = {1708-8283},
	doi = {10.1177/0883073815599258},
	author = {VanderVeen, Deborah K and Allred, Elizabeth N and Wallace, David K and Leviton, Alan and ELGAN Study Investigators}
}
@article {1364558,
	title = {Predictability of intraocular lens calculation and early refractive status: the Infant Aphakia Treatment Study},
	journal = {Arch Ophthalmol},
	volume = {130},
	number = {3},
	year = {2012},
	month = {2012 Mar},
	pages = {293-9},
	abstract = {OBJECTIVE: To report the accuracy of intraocular lens (IOL) power calculations and the early refractive status in pseudophakic eyes of infants in the Infant Aphakia Treatment Study. METHODS: Eyes randomized to receive primary IOL implantation were targeted for a postoperative refraction of +8.0 diopters (D) for infants 28 to 48 days old at surgery and +6.0 D for those 49 days or older to younger than 7 months at surgery using the Holladay 1 formula. Refraction 1 month after surgery was converted to spherical equivalent, and prediction error (PE; defined as the calculated refraction minus the actual refraction) and absolute PE were calculated. Baseline eye and surgery characteristics and A-scan quality were analyzed to compare their effect on PE. MAIN OUTCOME MEASURES: Prediction error. RESULTS: Fifty-six eyes underwent primary IOL implantation; 7 were excluded for lack of postoperative refraction (n = 5) or incorrect technique in refraction (n = 1) or biometry (n = 1). Overall mean (SD) absolute PE was 1.8 (1.3) D and mean (SD) PE was +1.0 (2.0) D. Absolute PE was less than 1 D in 41\% of eyes but greater than 2 D in 41\% of eyes. Mean IOL power implanted was 29.9 D (range, 11.5-40.0 D); most eyes (88\%) implanted with an IOL of 30.0 D or greater had less postoperative hyperopia than planned. Multivariate analysis revealed that only short axial length (\&lt;18 mm) was significant for higher PE. CONCLUSIONS: Short axial length correlates with higher PE after IOL placement in infants. Less hyperopia than anticipated occurs with axial lengths of less than 18 mm or high-power IOLs. Application to Clinical Practice Quality A-scans are essential and higher PE is common, with a tendency for less hyperopia than expected. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00212134.},
	keywords = {Cataract, Cataract Extraction, Child, Preschool, Follow-Up Studies, Humans, Hyperopia, Infant, Lens Implantation, Intraocular, Lenses, Intraocular, Postoperative Complications, Predictive Value of Tests, Refractometry, Visual Acuity},
	issn = {1538-3601},
	doi = {10.1001/archophthalmol.2011.358},
	author = {VanderVeen, Deborah K and Nizam, Azhar and Lynn, Michael J and Bothun, Erick D and McClatchey, Scott K and Weakley, David R and DuBois, Lindreth G and Lambert, Scott R and Infant Aphakia Treatment Study Group}
}
@article {1363216,
	title = {Early nutrition and weight gain in preterm newborns and the risk of retinopathy of prematurity},
	journal = {PLoS One},
	volume = {8},
	number = {5},
	year = {2013},
	month = {2013},
	pages = {e64325},
	abstract = {OBJECTIVE: To identify nutritional and weight gain limitations associated with retinopathy of prematurity (ROP) severity among very preterm newborns. PATIENTS AND METHODS: 1180 infants \&lt;28 weeks GA at birth with ROP examination results were grouped and analyzed by quartile of weekly total calorie, carbohydrate, protein, and lipid intake, as well as growth velocity between postnatal days 7 and 28 (adjusted for GA and birth weight Z-score). ROP was categorized by development of no, mild (},
	keywords = {Female, Humans, Infant Nutritional Physiological Phenomena, Infant, Extremely Premature, Infant, Newborn, Logistic Models, Male, Nutritional Status, Prospective Studies, Retinopathy of Prematurity, Risk Assessment, Risk Factors, Time Factors, Weight Gain},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0064325},
	author = {VanderVeen, Deborah K and Martin, Camilia R and Mehendale, Reshma and Allred, Elizabeth N and Dammann, Olaf and Leviton, Alan and ELGAN Study Investigators}
}
@article {1470996,
	title = {Anti-vascular endothelial growth factor intravitreal therapy for retinopathy of prematurity},
	journal = {Semin Perinatol},
	volume = {43},
	number = {6},
	year = {2019},
	month = {2019 Oct},
	pages = {375-380},
	abstract = {Retinopathy of prematurity treatment modalities have expanded over the years, from cryotherapy to laser therapy and now, anti-vascular endothelial factor (VEGF) therapy by intravitreal injection. Use of anti-VEGF treatment varies regionally and depends on multiple factors including severity and progression of ROP, availability of alternative treatments, experience of the local ophthalmologists, medical status of the infant, and expectations for long-term follow-up. While the advantages and disadvantages of anti-VEGF intravitreal treatment on the eye are relatively well-described, few studies provide information about potential long-term systemic effects of this treatment, which is known to transiently reduce systemic VEGF concentrations.},
	issn = {1558-075X},
	doi = {10.1053/j.semperi.2019.05.011},
	author = {VanderVeen, Deborah K and Cataltepe, Sule U}
}
@article {1647904,
	title = {Effective lens position and pseudophakic refraction prediction error at 10{\textonehalf} years of age in the Infant Aphakia Treatment Study},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Jul 19},
	abstract = {BACKGROUND: The refraction prediction error (PE) for infants with intraocular lens (IOL) implantation is large, possibly related to an effective lens position (ELP) that is different than in adult eyes. If these eyes still have nonadult ELPs as they age, this could result in persistently large PE. We aimed to determine whether ELP or biometry at age 10{\textonehalf} years correlated with PE in children enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: We compared the measured refraction of eyes randomized to primary IOL implantation to the "predicted refraction" calculated by the Holladay 1 formula, based on biometry at age 10{\textonehalf} years. Eyes with incomplete data or IOL exchange were excluded. The PE (predicted - measured refraction) and absolute PE were calculated. Measured anterior chamber depth (ACD) was used to assess the effect of ELP on PE. Multiple regression analysis was performed on absolute PE versus axial length, corneal power, rate of refractive growth, refractive error, and best-corrected visual acuity. RESULTS: Forty-three eyes were included. The PE was 0.63 {\textpm} 1.68 D; median absolute PE, 0.85 D (IQR, 1.83 D). The median absolute PE was greater when the measured ACD was used to calculate predicted refraction instead of the standard A-constant (1.88 D [IQR, 1.72] D vs 0.85 D [IQR, 1.83], resp. [P = 0.03]). Absolute PE was not significantly correlated with any other parameter. CONCLUSIONS: Variations in ELP did not contribute significantly to PE 10 years after infant cataract surgery.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.04.010},
	author = {VanderVeen, Deborah K and McClatchey, Thaddeus S and McClatchey, Scott K and Nizam, Azhar and Lambert, Scott R and Infant Aphakia Treatment Study Group}
}
@article {1635652,
	title = {Deviations From Age-Adjusted Normative Biometry Measures in Children Undergoing Cataract Surgery: Implications for Postoperative Target Refraction and IOL Power Selection},
	journal = {Am J Ophthalmol},
	volume = {239},
	year = {2022},
	month = {2022 07},
	pages = {190-201},
	abstract = {PURPOSE: To evaluate whether pediatric eyes that deviate from age-adjusted normative biometry parameters predict variation in myopic shift after cataract surgery. METHODS: This is a single institution longitudinal cohort study combining prospectively collected biometry data from normal eyes of children \&lt;10 years old with biometry data from eyes undergoing cataract surgery. Refractive data from patients with a minimum of 5 visits over >=5 years of follow-up were used to calculate myopic shift and rate of refractive growth. Cataractous eyes that deviated from the middle quartiles of the age-adjusted normative values for axial length and keratometry were studied for variation in myopic shift and rate of refractive growth to 5 years and last follow-up visit. Multivariable analysis was performed to determine the association between myopic shift and rate of refractive growth and factors of age, sex, laterality, keratometry, axial length, intraocular lens power, and follow-up length. RESULTS: Normative values were derived from 100 eyes; there were 162 eyes in the cataract group with a median follow-up of 9.6 years (interquartile range: 7.3-12.2 years). The mean myopic shift ranged from 5.5 D (interquartile range: 6.3-3.5 D) for 0- to 2-year-olds to 1.0 D (interquartile range: 1.5-0.6 D) for 8- to 10-year-olds. Multivariable analysis showed that more myopic shift was associated with younger age (P \&lt; .001), lower keratometry (P\&nbsp;=\&nbsp;.01), and male gender (P\&nbsp;=\&nbsp;.027); greater rate of refractive growth was only associated with lower keratometry measures (P\&nbsp;=\&nbsp;.001). CONCLUSIONS: Age-based tables for intraocular lens power selection are useful, and modest adjustments can be considered for eyes with lower keratometry values than expected for age.},
	keywords = {Biometry, Cataract, Cataract Extraction, Child, Child, Preschool, Cornea, Humans, Lenses, Intraocular, Longitudinal Studies, Male, Myopia, Phacoemulsification, Refraction, Ocular, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.02.022},
	author = {VanderVeen, Deborah K and Oke, Isdin and Nihalani, Bharti R}
}
@article {1360124,
	title = {Use of Orthokeratology for the Prevention of Myopic Progression in Children: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {126},
	number = {4},
	year = {2019},
	month = {2019 Apr},
	pages = {623-636},
	abstract = {PURPOSE: To review the published evidence to evaluate the ability of orthokeratology (Ortho-K) treatment to reduce myopic progression in children and adolescents compared with the use of spectacles or daytime contact lenses for standard refractive correction. METHODS: Literature searches of the PubMed database, the Cochrane Library, and the databases of clinical trials were last conducted on August 21, 2018, with no date restrictions but limited to articles published in English. These searches yielded 162 citations, of which 13 were deemed clinically relevant for full-text review and inclusion in this assessment. The panel methodologist then assigned a level of evidence rating to the selected studies. RESULTS: The 13 articles selected for inclusion include 3 prospective, randomized clinical trials; 7 nonrandomized, prospective comparative studies; and 3 retrospective case series. One study provided level I evidence, 11 studies provided level II evidence, and 1 study provided level III evidence. Most studies were performed in populations of Asian ethnicity. Change in axial length was the primary outcome for 10 of 13 studies and change in refraction was the primary outcome for 3 of 13 studies. In these studies, Ortho-K typically reduced axial elongation by approximately 50\% over a 2-year study period. This corresponds to average axial length change values of approximately 0.3 mm for Ortho-K patients compared with 0.6 mm for control patients, which corresponds to a typical difference in refraction of approximately 0.5 diopters (D). Younger age groups and individuals with larger than average pupil size may have a greater effect with Ortho-K. Rebound can occur after discontinuation or change to alternative refractive treatment. CONCLUSIONS: Orthokeratology may be effective in slowing myopic progression for children and adolescents, with a potentially greater effect when initiated at an early age (6-8 years). Safety remains a concern because of the risk of potentially blinding microbial keratitis from contact lens wear.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.11.026},
	author = {VanderVeen, Deborah K and Kraker, Raymond T and Pineles, Stacy L and Hutchinson, Amy K and Wilson, Lorri B and Galvin, Jennifer A and Lambert, Scott R}
}
@article {1179171,
	title = {Teaching Video NeuroImages: Bilateral abducens ocular neuromyotonia},
	journal = {Neurology},
	volume = {89},
	number = {10},
	year = {2017},
	month = {2017 Sep 05},
	pages = {e128},
	issn = {1526-632X},
	doi = {10.1212/WNL.0000000000004338},
	author = {Vanikieti, Kavin and Rizzo, Joseph F}
}
@article {1664950,
	title = {Genomic evidence of SARS-CoV-2 reinfection cases in southern Brazil},
	journal = {Arch Virol},
	volume = {168},
	number = {1},
	year = {2023},
	month = {2023 Jan 03},
	pages = {19},
	abstract = {Cases of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported worldwide. We investigated reinfection cases in a set of more than 30,000 samples, and the SARS-CoV-2 genomes from selected samples from four patients with at least two positive diagnoses with an interval >= 45 days between tests were sequenced and analyzed. Comparative genomic and phylogenetic analysis confirmed three reinfection cases and suggested that the fourth one was caused by a virus of the same lineage. Viral sequencing is crucial for understanding the natural course of reinfections and for planning public health strategies for management of COVID-19.},
	keywords = {Brazil, COVID-19, Genomics, Humans, Phylogeny, Reinfection, SARS-CoV-2},
	issn = {1432-8798},
	doi = {10.1007/s00705-022-05648-8},
	author = {Varela, Ana Paula Muterle and Sant{\textquoteright}Anna, Fernando Hayashi and Dos Santos, Ani{\'u}sca Vieira and Prichula, Janira and Comerlato, Juliana and Dos Santos, Giovana Tavares and Wendland, Eliana}
}
@article {1517207,
	title = {Infrared attenuated total reflection spectroscopic surface analysis of bovine-tail intervertebral discs after UV-light-activated riboflavin-induced collagen crosslinking},
	journal = {J Biophotonics},
	year = {2020},
	month = {2020 Jun 26},
	pages = {e202000110},
	abstract = {The tensile strength of the intervertebral disc (IVD) is mainly maintained by collagen cross-links. Loss of collagen cross-linking combined with other age-related degenerative processes contributes to tissue weakening, biomechanical failure, disc herniation and pain. Exogenous collagen cross-linking has been identified as an effective therapeutic approach for restoring IVD tensile strength. The current state-of-the-art method to assess the extent of collagen cross-linking in tissues requires destructive procedures and high-performance liquid chromatography (HPLC). In this study, we investigated the utility of infrared attenuated total reflection (IR-ATR) spectroscopy as a non-destructive analytical strategy to rapidly evaluate the extent of UV-light-activated riboflavin (B2)-induced collagen crosslinking (UVA-CXL) in bovine IVD samples. Thirty five fresh bovine-tail IVD samples were equally divided into five treatment groups: (i) untreated, (ii) cell culture medium DMEM only, (iii) B2 only, (iv) UV-light only, and (v) UV-light-B2. A total of 674 measurements have been acquired, and were analyzed via partial least squares discriminant analysis. This classification scheme unambiguously identified individual classes with a sensitivity \&gt;91\% and specificity \&gt;92\%. The obtained results demonstrate that IR-ATR spectroscopy reliably differentiates between different treatment categories, and promises an excellent tool for potential in vivo, non-destructive, and real-time assessment of exogenous IVD crosslinking. This article is protected by copyright. All rights reserved.},
	issn = {1864-0648},
	doi = {10.1002/jbio.202000110},
	author = {Vasilikos, Ioannis and Haas, Julian and Teixeira, Graciosa Q and Nothelfer, Julia and Neidlinger-Wilke, Cornelia and Wilke, Hans-Joachim and Seitz, Andreas and Vavvas, Demetrios G and Zentner, Josef and Beck, Juergen and Hubbe, Ulrich and Mizaikoff, Boris}
}
@article {1319486,
	title = {Reply to Vickers: Pharmacogenetics and progression to neovascular age-related macular degeneration-Evidence supporting practice change},
	journal = {Proc Natl Acad Sci U S A},
	volume = {115},
	number = {25},
	year = {2018},
	month = {2018 Jun 19},
	pages = {E5640-E5641},
	issn = {1091-6490},
	doi = {10.1073/pnas.1804781115},
	author = {Vavvas, Demetrios G and Small, Kent W and Awh, Carl and Zanke, Brent W and Tibshirani, Robert J and Kustra, Rafal}
}
@article {1309969,
	title = {Lens regeneration in children},
	journal = {Nature},
	volume = {556},
	number = {7699},
	year = {2018},
	month = {2018 Apr 04},
	pages = {E2-E3},
	issn = {1476-4687},
	doi = {10.1038/nature26149},
	author = {Vavvas, Demetrios G and Dryja, Thaddeus P and Wilson, M Edward and Olsen, Timothy W and Shah, Ankoor and Jurkunas, Ula and Pineda, Roberto and Poulaki, Vasiliki and Palioura, Sotiria and Veldman, Peter and Moreno-Monta{\~n}{\'e}s, Javier and Pinazo-Duran, Maria D and Pastor, Jos{\'e} Carlos and Tsilimbaris, Miltiadis and Rhee, Douglas and Colby, Kathryn and Hunter, David G and Thanos, Solon and Sakamoto, Taiji and Pasquale, Louis R and Miller, Joan W and Vanderveen, Deborah and Lambert, Scott R}
}
@article {1295882,
	title = {CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation},
	journal = {Proc Natl Acad Sci U S A},
	year = {2018},
	month = {2018 Jan 08},
	abstract = {We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been treated with placebo or the AREDS formulation were evaluated for differences in the risk of progression to NV as a function of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotype groups. We used published genetic grouping: a two-SNP haplotype risk-calling algorithm to assess CFH, and either the single SNP rs10490924 or 372_815del443ins54 to mark ARMS2 risk. Progression risk was determined using the Cox proportional hazard model. Genetics-treatment interaction on NV risk was assessed using a multiiterative bootstrap validation analysis. We identified strong interaction of genetics with AREDS formulation treatment on the development of NV. Individuals with high CFH and no ARMS2 risk alleles and taking the AREDS formulation had increased progression to NV compared with placebo. Those with low CFH risk and high ARMS2 risk had decreased progression risk. Analysis of CFH and ARMS2 genotype groups from a validation dataset reinforces this conclusion. Bootstrapping analysis confirms the presence of a genetics-treatment interaction and suggests that individual treatment response to the AREDS formulation is largely determined by genetics. The AREDS formulation modifies the risk of progression to NV based on individual genetics. Its use should be based on patient-specific genotype.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1718059115},
	author = {Vavvas, Demetrios G and Small, Kent W and Awh, Carl C and Zanke, Brent W and Tibshirani, Robert J and Kustra, Rafal}
}
@article {691751,
	title = {Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment.},
	journal = {EBioMedicine},
	volume = {5},
	year = {2016},
	month = {2016 Mar},
	pages = {198-203},
	abstract = {IMPORTANCE: Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage. OBJECTIVE: We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD. DESIGN: Pilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80\&nbsp;mg of atorvastatin daily and were monitored at baseline and every 3\&nbsp;months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women). RESULTS: Twenty-three subjects completed a minimum follow-up of 12\&nbsp;months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+\&nbsp;3.3 letters, p\&nbsp;=\&nbsp;0.06) in 10 patients. No subjects progressed to advanced neovascular AMD. CONCLUSIONS: High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.},
	issn = {2352-3964},
	doi = {10.1016/j.ebiom.2016.01.033},
	author = {Vavvas, Demetrios G and Daniels, Anthony B and Kapsala, Zoi G and Goldfarb, Jeremy W and Ganotakis, Emmanuel and Loewenstein, John I and Young, Lucy H and Gragoudas, Evangelos S and Eliott, Dean and Kim, Ivana K and Tsilimbaris, Miltiadis K and Miller, Joan W}
}
@article {1522722,
	title = {Concerns about the interpretation of OCT and fundus findings in COVID-19 patients in recent Lancet publication},
	journal = {Eye (Lond)},
	volume = {34},
	number = {12},
	year = {2020},
	month = {2020 12},
	pages = {2153-2154},
	keywords = {Betacoronavirus, Coronavirus Infections, COVID-19, Fundus Oculi, Humans, Pandemics, Pneumonia, Viral, SARS-CoV-2, Tomography, Optical Coherence},
	issn = {1476-5454},
	doi = {10.1038/s41433-020-1084-9},
	author = {Vavvas, Demetrios G and Sarraf, David and Sadda, Srinivas R and Eliott, Dean and Ehlers, Justis P and Waheed, Nadia K and Morizane, Yuki and Sakamoto, Taiji and Tsilimbaris, Miltiadis and Miller, John B}
}
@article {1363217,
	title = {Anti-VEGF in retinopathy of prematurity, need to titrate},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {3},
	year = {2013},
	month = {2013 Mar 21},
	keywords = {Animals, Antibodies, Female, Humans, Neovascularization, Pathologic, Oxygen, Recombinant Fusion Proteins, Retina, Retinal Diseases, Retinal Vessels, Retinopathy of Prematurity, Vascular Endothelial Growth Factor A},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-11948},
	author = {Vavvas, Demetrios G}
}
@article {1297786,
	title = {Limbal Stem Cell Deficiency - Demography And Underlying Causes},
	journal = {Am J Ophthalmol},
	year = {2018},
	month = {2018 Jan 26},
	abstract = {PURPOSE: To determine the demographic features of patients affected by limbal stem cell deficiency (LSCD), and to identify the underlying causes of LSCD DESIGN: Retrospective, multi-center case series SETTING: Two large tertiary care ophthalmology hospitals SUBJECTS: Patients with a diagnosis of LSCD presenting from January 1, 2005 to December 31, 2014 METHODS: Records of patients with a clinical diagnosis of LSCD were reviewed. Demographic details and clinical features at presentation, as well as the underlying cause of LSCD (if identified) were noted. Descriptive statistical analysis and chart preparation were done. MAIN OUTCOME MEASURES: Type of LSCD (unilateral or bilateral), age and sex of patients, extent of LSCD (clock hours of limbus involved) and underlying cause of LSCD RESULTS: We found 1331 patients with LSCD in the ten year period under study. Unilateral LSCD was more common (791 patients) than bilateral LSCD (540 patients). Out of 1331 patients, 875 (65.74\%) were male. The median age of patients was 24 years. Extent of LSCD could be determined in 1849 eyes, of which 1239 eyes (67\%) had total LSCD. The underlying cause of LSCD could be identified in 1512 eyes. In cases of unilateral LSCD, ocular surface burns was the commonest identifiable cause ( 83.73\%). The leading identifiable causes of bilateral LSCD were ocular surface burns (29.95\%), allergic conjunctivitis (29.48\%), Stevens Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (23.11\%), aniridia (9.43\%) and mucous membrane pemphigoid (3.54\%). Lime ("chuna") injury was responsible for ocular surface burns in 352 (62.08\%) out of 567 cases in which the agent was identified. CONCLUSIONS: In our study, unilateral LSCD was more common than bilateral LSCD. Young males were commonly affected, with a majority of eyes suffering from total LSCD. Overall, ocular surface burns are the leading cause of LSCD.Unilateral and bilateral LSCD had a markedly different distribution of causes, necessitating different approaches to management.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.01.020},
	author = {Vazirani, Jayesh and Nair, Dhanyasree and Shanbhag, Swapna and Wurity, Siva and Ranjan, Abhishek and Sangwan, Virender}
}
@article {635001,
	title = {Autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency: multicentre results.},
	journal = {Br J Ophthalmol},
	volume = {100},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {1416-20},
	abstract = {PURPOSE: To report outcomes of autologous simple limbal epithelial transplantation (SLET) performed for unilateral limbal stem cell deficiency (LSCD) at multiple centres worldwide. METHODS: In this retrospective, multicentre, interventional case series, records of patients who had undergone autologous SLET for unilateral LSCD, with a minimum of 6 months of follow-up, were reviewed. The primary outcome measure was clinical success, defined as a completely epithelised, avascular corneal surface. Kaplan-Meier survival curves were constructed and survival probability was calculated. A Cox proportional hazards analysis was done to assess association of preoperative characteristics with risk of failure. Secondary outcome measures included the percentage of eyes achieving visual acuity of 20/200 or better, percentage of eyes gaining two or more Snellen lines and complications encountered. RESULTS: 68 eyes of 68 patients underwent autologous SLET, performed across eight centres in three countries. Clinical success was achieved in 57 cases (83.8\%). With a median follow-up of 12 months, survival probability exceeded 80\%. Presence of symblepharon (HR 5.8) and simultaneous keratoplasty (HR 10.8) were found to be significantly associated with a risk of failure. 44 eyes (64.7\%) achieved a visual acuity of 20/200 or better, and 44 eyes (64.7\%) gained two or more Snellen lines. Focal recurrences of pannus were noted in 21 eyes (36.8\%) with clinical success. CONCLUSION: Autologous SLET is an effective and safe modality for treatment of unilateral LSCD. Clinical success rates and visual acuity improvement are equal to or better than those reported with earlier techniques.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2015-307348},
	author = {Vazirani, Jayesh and Ali, Mohammed Hasnat and Sharma, Namrata and Gupta, Nidhi and Mittal, Vikas and Atallah, Marwan and Amescua, Guillermo and Chowdhury, Tuhin and Abdala-Figuerola, Alexandra and Ramirez-Miranda, Arturo and Navas, Alejandro and Graue-Hern{\'a}ndez, Enrique O and Chodosh, James}
}
@article {1364559,
	title = {Two cases of cosmetic iris implant explantation secondary to uveitis, glaucoma, and corneal decompensation},
	journal = {Arch Ophthalmol},
	volume = {130},
	number = {6},
	year = {2012},
	month = {2012 Jun},
	pages = {787-9},
	keywords = {Adult, Anterior Eye Segment, Cell Count, Corneal Diseases, Corneal Endothelial Cell Loss, Cosmetic Techniques, Device Removal, Female, Glaucoma, Angle-Closure, Humans, Iris, Prostheses and Implants, Silicone Elastomers, Uveitis},
	issn = {1538-3601},
	doi = {10.1001/archophthalmol.2011.2594},
	author = {Veldman, Peter B and Behlau, Irmgard and Soriano, Eduardo and Starling, Jay C and Pineda, Roberto}
}
@article {541351,
	title = {Stamping an S on DMEK Donor Tissue to Prevent Upside-Down Grafts: Laboratory Validation and Detailed Preparation Technique Description.},
	journal = {Cornea},
	volume = {34},
	number = {9},
	year = {2015},
	month = {2015 Sep},
	pages = {1175-8},
	abstract = {PURPOSE: To report endothelial cell loss (ECL) caused by a novel S-stamp preparation technique for Descemet membrane endothelial keratoplasty (DMEK). METHODS: Six cadaveric human corneas were prepared for DMEK transplantation using a single standardized technique, including the application of a dry ink gentian violet S-stamp to the stromal side of Descemet membrane. Endothelial cell death was evaluated and quantified using computerized analysis of vital dye staining. RESULTS: ECL caused by the S-stamp was 0.6\% (range 0.1\%-1.0\%), which comprised less than one-tenth of the total ECL caused by our preparation of the DMEK graft from the start to finish, including recovery, prestripping, S-stamping, and trephination (13.7\% total ECL, range 9.9\%-17.6\%). CONCLUSIONS: Our novel S-stamp donor tissue preparation technique is intuitive to learn and holds the promise of preventing iatrogenic primary graft failure due to upside-down grafts without causing unacceptable increases in ECL.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000522},
	author = {Veldman, Peter B and Dye, Philip K and Holiman, Jeffrey D and Mayko, Zachary M and S{\'a}les, Christopher S and Straiko, Michael D and Stoeger, Christopher G and Terry, Mark A}
}
@article {1806521,
	title = {Corrigendum to "Future directions in managing aniridia-associated keratopathy" [Surv Ophthalmol 68 (2023) 940-956]},
	journal = {Surv Ophthalmol},
	volume = {69},
	number = {2},
	year = {2024},
	month = {2024 Mar-Apr},
	pages = {300-301},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2024.01.001},
	author = {van Velthoven, Arianne J H and Utheim, Tor P and Notara, Maria and Bremond-Gignac, Dominique and Figueiredo, Francisco C and Skottman, Heli and Aberdam, Daniel and Daniels, Julie T and Ferrari, Giulio and Grupcheva, Christina and Koppen, Carina and Parekh, Mohit and Ritter, Thomas and Romano, Vito and Ferrari, Stefano and Cursiefen, Claus and Lagali, Neil and LaPointe, Vanessa L S and Dickman, Mor M}
}
@article {1698221,
	title = {Future directions in managing aniridia-associated keratopathy},
	journal = {Surv Ophthalmol},
	volume = {68},
	number = {5},
	year = {2023},
	month = {2023 Sep-Oct},
	pages = {940-956},
	abstract = {Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2023.04.003},
	author = {van Velthoven, Arianne J H and Utheim, Tor P and Notara, Maria and Bremond-Gignac, Dominique and Figueiredo, Francisco C and Skottman, Heli and Aberdam, Daniel and Daniels, Julie T and Ferrari, Giulio and Grupcheva, Christina and Koppen, Carina and Parekh, Mohit and Ritter, Thomas and Romano, Vito and Ferrari, Stefano and Cursiefen, Claus and Lagali, Neil and LaPointe, Vanessa L S and Dickman, Mor M}
}
@article {1653589,
	title = {Impaired Extraocular Muscle Innervation Is Present Before Eye Opening in a Mouse Model of Infantile Nystagmus Syndrome},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {63},
	number = {10},
	year = {2022},
	month = {2022 09 01},
	pages = {4},
	abstract = {Purpose: To determine if extraocular muscles (EOMs) from mice with nystagmus show abnormalities in myofiber composition and innervation, as seen in EOMs from human nystagmus patients, and to determine when in development those changes occur. Methods: Balb/c albino mice were crossed to pigmented mice to generate heterozygous mice, which were mated to create experimental litters containing albinos and wild-type controls. Orbits were harvested from adult animals (12 weeks old); on postnatal day (P)0, P10, P14, and P21; and from 6-week-old animals. EOM sections were collected from the intraorbital portion of the muscles. Sections were immunostained for slow and fast myosin and for neuromuscular junctions (NMJs). The proportion of each myofiber subtype and the density and size of NMJs were quantified. Initial innervation patterns were assessed using whole-mount immunostaining of embryonic day (E)13.5 embryos expressing IslMN:GFP. Results: Adult albino EOMs display an increased proportion of slow myofibers, larger slow myofibers, and a decreased density of NMJs-similar to human nystagmus patients. The percentage of NMJs on slow myofibers is also lower in albino animals. The initial innervation pattern of the incoming ocular motor neurons is normal in E13.5 albino embryos. Differences in the proportion of slow and fast myofiber subtypes are present as early as P14, and a lower percentage of NMJs on slow myofibers is present by P21. There is a lower density of NMJs on albino EOMs as early as P10, prior to eye opening. Conclusions: Changes in NMJ development observed before eye opening indicate that nystagmus is not solely secondary to poor vision.},
	keywords = {Adult, Animals, Disease Models, Animal, Eye, Humans, Mice, Motor Neurons, Neuromuscular Junction, Nystagmus, Pathologic, Oculomotor Muscles},
	issn = {1552-5783},
	doi = {10.1167/iovs.63.10.4},
	author = {Vemula, Sampath Kumar and Kim, Seoyoung A and Muvavarirwa, Tapiwa and Bell, Jessica L and Whitman, Mary C}
}
@article {1538317,
	title = {Paraneoplastic Pemphigus Associated with Bilateral Corneal Perforations in Follicular Dendritic Cell Sarcoma},
	journal = {Ocul Immunol Inflamm},
	year = {2020},
	month = {2020 Oct 13},
	pages = {1-3},
	abstract = {PURPOSE: To describe a case of paraneoplastic pemphigus (PNP) presenting as spontaneous bilateral corneal perforations in a patient with follicular dendritic cell sarcoma. METHODS: Retrospective chart review Results: A 73-year-old Greek woman with a history of follicular dendritic cell sarcoma (FDCS) presented with bilateral corneal perforations and a cicatrizing conjunctivitis. Her diagnosis was consistent with PNP with corneal and conjunctival involvement after a change in her chemotherapy regimen from intravenous cyclophosphamide to gemcitabine. She was treated with a multilayered amniotic membrane in the right eye and cyanoacrylate glue in the left eye. Systemic intravenous cyclophosphamide and oral prednisone were re-started. Both perforations healed but the patient passed away soon after precluding further follow-up. CONCLUSIONS: Ocular manifestations of PNP can rarely present with spontaneous corneal perforations. This is the first case of FDCS-associated PNP with corneal involvement. Such cases should be diagnosed expediently and managed with aggressive systemic immunosuppressive therapy.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1828491},
	author = {Venkateswaran, Nandini and Klavdianou, Olga and Kondylis, Georgios and Kosmidis, Ioannis and Palioura, Sotiria}
}
@article {1593871,
	title = {The role of imaging technologies for ocular surface tumors},
	journal = {Curr Opin Ophthalmol},
	volume = {32},
	number = {4},
	year = {2021},
	month = {2021 07 01},
	pages = {369-378},
	abstract = {PURPOSE OF REVIEW: This review will discuss the utility of high-resolution anterior segment optical coherence tomography (HR-OCT), in-vivo confocal microscopy (IVCM) and ultrasound biomicroscopy (UBM) in characterizing and diagnosing various ocular surface tumors, namely ocular surface squamous neoplasia (OSSN), conjunctival lymphoma and conjunctival melanoma. The strengths and limitations of each imaging modality will be discussed along with the characteristics findings of each lesion on each imaging platform. RECENT FINDINGS: HR-OCT can consistently be utilized in the clinic setting to distinguish between epithelial ocular surface tumors such as OSSN as compared with subepithelial tumors such as conjunctival lymphoma and conjunctival melanoma given their distinctive findings. IVCM can be used as an adjunct to HR-OCT to obtain cellular and surface characteristics, whereas UBM can be used to assess tumor depth and thickness for larger and highly pigmented lesions as well as to detect intraocular invasion. SUMMARY: HR-OCT, IVCM and UBM are all helpful imaging modalities to diagnose and characterize various ocular surface tumors and can serve as valuable adjuncts to monitor treatment response and assess for recurrence ocular surface tumors.},
	keywords = {Conjunctiva, Conjunctival Neoplasms, Diagnostic Imaging, Humans, Microscopy, Acoustic, Microscopy, Confocal, Tomography, Optical Coherence},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000771},
	author = {Venkateswaran, Nandini and Sripawadkul, Wathanee and Karp, Carol L}
}
@article {1538335,
	title = {Rods Contribute to Visual Behavior in Larval Zebrafish},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {12},
	year = {2020},
	month = {2020 Oct 01},
	pages = {11},
	abstract = {Purpose: Although zebrafish rods begin to develop as early as 2 days postfertilization (dpf), they are not deemed anatomically mature and functional until 15 to 21 dpf. A recent study detected a small electroretinogram (ERG) from rods in a cone mutant called no optokinetic response f (nof) at 5 dpf, suggesting that young rods are functional. Whether they can mediate behavioral responses in larvae is unknown. Methods: We first confirmed rod function by measuring nof ERGs under photopic and scotopic illumination at 6 dpf. We evaluated the role of rods in visual behaviors using two different assays: the visual-motor response (VMR) and optokinetic response (OKR). We measured responses from wild-type (WT) larvae and nof mutants under photopic and scotopic illuminations at 6 dpf. Results: Nof mutants lacked a photopic ERG. However, after prolonged dark adaptation, they displayed scotopic ERGs. Compared with WT larvae, the nof mutants displayed reduced VMRs. The VMR difference during light onset gradually diminished with decreased illumination and became nearly identical at lower light intensities. Additionally, light-adapted nof mutants did not display an OKR, whereas dark-adapted nof mutants displayed scotopic OKRs. Conclusions: Because the nof mutants lacked a photopic ERG but displayed scotopic ERGs after dark adaptation, the mutants clearly had functional rods. WT larvae and the nof mutants displayed comparable scotopic light-On VMRs and scotopic OKRs after dark adaptation, suggesting that these responses were driven primarily by rods. Together, these observations indicate that rods contribute to zebrafish visual behaviors as early as 6 dpf.},
	issn = {1552-5783},
	doi = {10.1167/iovs.61.12.11},
	author = {Venkatraman, Prahatha and Mills-Henry, Ishara and Padmanabhan, Karthik Ramaswamy and Pascuzzi, Pete and Hassan, Menna and Zhang, Jingyi and Zhang, Xinlian and Ma, Ping and Pang, Chi Pui and Dowling, John E and Zhang, Mingzhi and Leung, Yuk Fai}
}
@article {410366,
	title = {Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry.},
	journal = {Genet Med},
	volume = {17},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {285-90},
	abstract = {PURPOSE: Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1\% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. METHODS: We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. RESULTS: We identified the MAK and DHDDS mutations homozygously in only 2.1\% and 0.8\%, respectively, of patients of mixed ethnicity, but in 25.7\% and 8.6\%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. CONCLUSION: In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.Genet Med 17 4, 285-290.},
	issn = {1530-0366},
	doi = {10.1038/gim.2014.132},
	author = {Venturini, Giulia and Koskiniemi-Kuendig, Hanna and Harper, Shyana and Berson, Eliot L and Rivolta, Carlo}
}
@article {1125401,
	title = {Blur Adaptation to Central Retinal Disease},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {9},
	year = {2017},
	month = {2017 Jul 01},
	pages = {3646-3655},
	abstract = {Purpose: The long-term, low-resolution vision experienced by individuals affected by retinal disease that causes central vision loss (CVL) may change their perception of blur through adaptation. This study used a short-term adaptation paradigm to evaluate adaptation to blur and sharpness in patients with CVL. Methods: A variation of Webster{\textquoteright}s procedure was used to measure the point of subjective neutrality (PSN). The image that appeared normal after adaptation to each of seven blur and sharpness levels (PSN) was measured in 12 patients with CVL (20/60 to 20/320) and 5 subjects with normal sight (NS). Patients with CVL used a preferred retinal locus to view the images. Small control studies investigated the effects of long-term and medium-term (1 hour) defocus and diffusive blur. Results: Adaptation was reliably measured in patients with CVL and in the peripheral vision of NS subjects. The shape of adaptation curves was similar in patients with CVL and both central and peripheral vision of NS subjects. No statistical correlations were found between adaptation and age, visual acuity, retinal eccentricity, or contrast sensitivity. Long-term blur experience by a non-CVL myopic participant caused a shift in the adaptation function. Conversely, medium-term adaptation did not cause a shift in the adaptation function. Conclusions: Blur and sharp short-term adaptation occurred in peripheral vision of normal and diseased retinas. In most patients with CVL, neither adaptation nor blur perception was affected by long-term attention to peripheral low-resolution vision. The impact of blur/sharp adaptation on the benefit of image enhancement techniques for patients with CVL is discussed.},
	keywords = {Adaptation, Ocular, Adult, Aged, Aged, 80 and over, Contrast Sensitivity, Female, Humans, Male, Middle Aged, Myopia, Refraction, Ocular, Retinal Diseases, Vision Disorders, Visual Acuity, Visual Perception, Young Adult},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20849},
	author = {Vera-Diaz, Fuensanta A and Woods, Russell L and Peli, Eli}
}
@article {913546,
	title = {Epistatic Gene-Based Interaction Analyses for Glaucoma in eMERGE and NEIGHBOR Consortium.},
	journal = {PLoS Genet},
	volume = {12},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {e1006186},
	abstract = {Primary open angle glaucoma (POAG) is a complex disease and is one of the major leading causes of blindness worldwide. Genome-wide association studies have successfully identified several common variants associated with glaucoma; however, most of these variants only explain a small proportion of the genetic risk. Apart from the standard approach to identify main effects of variants across the genome, it is believed that gene-gene interactions can help elucidate part of the missing heritability by allowing for the test of interactions between genetic variants to mimic the complex nature of biology. To explain the etiology of glaucoma, we first performed a genome-wide association study (GWAS) on glaucoma case-control samples obtained from electronic medical records (EMR) to establish the utility of EMR data in detecting non-spurious and relevant associations; this analysis was aimed at confirming already known associations with glaucoma and validating the EMR derived glaucoma phenotype. Our findings from GWAS suggest consistent evidence of several known associations in POAG. We then performed an interaction analysis for variants found to be marginally associated with glaucoma (SNPs with main effect p-value \&lt;0.01) and observed interesting findings in the electronic MEdical Records and GEnomics Network (eMERGE) network dataset. Genes from the top epistatic interactions from eMERGE data (Likelihood Ratio Test i.e. LRT p-value \&lt;1e-05) were then tested for replication in the NEIGHBOR consortium dataset. To replicate our findings, we performed a gene-based SNP-SNP interaction analysis in NEIGHBOR and observed significant gene-gene interactions (p-value \&lt;0.001) among the top 17 gene-gene models identified in the discovery phase. Variants from gene-gene interaction analysis that we found to be associated with POAG explain 3.5\% of additional genetic variance in eMERGE dataset above what is explained by the SNPs in genes that are replicated from previous GWAS studies (which was only 2.1\% variance explained in eMERGE dataset); in the NEIGHBOR dataset, adding replicated SNPs from gene-gene interaction analysis explain 3.4\% of total variance whereas GWAS SNPs alone explain only 2.8\% of variance. Exploring gene-gene interactions may provide additional insights into many complex traits when explored in properly designed and powered association studies.},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1006186},
	author = {Verma, Shefali Setia and Cooke Bailey, Jessica N and Lucas, Anastasia and Bradford, Yuki and Linneman, James G and Hauser, Michael A and Pasquale, Louis R and Peissig, Peggy L and Brilliant, Murray H and McCarty, Catherine A and Haines, Jonathan L and Wiggs, Janey L and Vrabec, Tamara R and Tromp, Gerard and Ritchie, Marylyn D and eMERGE Network and NEIGHBOR Consortium}
}
@article {1798496,
	title = {A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma},
	journal = {Cell},
	volume = {187},
	number = {2},
	year = {2024},
	month = {2024 Jan 18},
	pages = {464-480.e10},
	abstract = {Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.},
	keywords = {Black People, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle, Humans, Polymorphism, Single Nucleotide},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2023.12.006},
	author = {Verma, Shefali S and Gudiseva, Harini V and Chavali, Venkata R M and Salowe, Rebecca J and Bradford, Yuki and Guare, Lindsay and Lucas, Anastasia and Collins, David W and Vrathasha, Vrathasha and Nair, Rohini M and Rathi, Sonika and Zhao, Bingxin and He, Jie and Lee, Roy and Zenebe-Gete, Selam and Bowman, Anita S and McHugh, Caitlin P and Zody, Michael C and Pistilli, Maxwell and Khachatryan, Naira and Daniel, Ebenezer and Murphy, Windell and Henderer, Jeffrey and Kinzy, Tyler G and Iyengar, Sudha K and Peachey, Neal S and Taylor, Kent D and Guo, Xiuqing and Chen, Yii-Der Ida and Zangwill, Linda and Girkin, Christopher and Ayyagari, Radha and Liebmann, Jeffrey and Chuka-Okosa, Chimd M and Williams, Susan E and Akafo, Stephen and Budenz, Donald L and Olawoye, Olusola O and Ramsay, Michele and Ashaye, Adeyinka and Akpa, Onoja M and Aung, Tin and Wiggs, Janey L and Ross, Ahmara G and Cui, Qi N and Addis, Victoria and Lehman, Amanda and Miller-Ellis, Eydie and Sankar, Prithvi S and Williams, Scott M and Ying, Gui-Shuang and Bailey, Jessica Cooke and Rotter, Jerome I and Weinreb, Robert and Khor, Chiea Chuen and Hauser, Michael A and Ritchie, Marylyn D and O{\textquoteright}Brien, Joan M}
}
@article {1137916,
	title = {Bilateral multiple evanescent white dot syndrome},
	journal = {Int Ophthalmol},
	volume = {38},
	number = {5},
	year = {2018},
	month = {2018 Oct},
	pages = {2153-2158},
	abstract = {PURPOSE: To present a single case of bilateral multiple evanescent white dot syndrome (MEWDS). METHODS: A single case with three months of follow-up using imaging studies including fundus color photography (FP), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), en face SD-OCT and optical coherence tomography angiography (OCTA) is presented. RESULTS: The patient presented with bilateral MEWDS, ultimately with complete resolution of symptoms. FP revealed foveal granularity and white punctate deep retinal spots, FA found early wreath-like hyperfluorescence, while ICGA showed hypofluorescent dots and spots in the early and late stages. FAF showed areas of hyperautofluorescence. SD-OCT revealed disruption of the ellipsoid zone (EZ) and accumulation of hyperreflective material of variable size and shape. En face SD-OCT demonstrated hyporeflective areas corresponding to areas of EZ disruption as well as hyperreflective dots in the outer nuclear layer. OCTA showed areas of photoreceptor slab black-out corresponding to areas of EZ disruption and light areas of flow void or flow disturbance in the choriocapillaris slab. CONCLUSIONS: This case represents an unusual case of bilateral MEWDS with complete resolution within three months.},
	keywords = {Choroiditis, Female, Fluorescein Angiography, Fovea Centralis, Fundus Oculi, Humans, Syndrome, Tomography, Optical Coherence, Young Adult},
	issn = {1573-2630},
	doi = {10.1007/s10792-017-0673-5},
	author = {Veronese, Chiara and Maiolo, Chiara and Morara, Mariachiara and Armstrong, Grayson W and Ciardella, Antonio P}
}
@article {669321,
	title = {OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY TO ASSESS PIGMENT EPITHELIAL DETACHMENT.},
	journal = {Retina},
	volume = {36},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {645-50},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000914},
	author = {Veronese, Chiara and Maiolo, Chiara and Morara, Mariachiara and Armstrong, Grayson W and Ciardella, Antonio P}
}
@article {1043296,
	title = {MULTIMODAL IMAGING IN VORTEX VEIN VARICES},
	journal = {Retin Cases Brief Rep},
	volume = {13},
	number = {3},
	year = {2019},
	month = {2019 Summer},
	pages = {260-265},
	abstract = {PURPOSE: The aim of this study is to describe the clinical presentation of vortex vein varices with multimodal imaging. METHODS: The authors carried out a retrospective case series of eight patients (7 female, 1 male) with an average age of 60.2 years (min 8, max 84, median 68.5) presenting with vortex vein varices. All patients were evaluated at the Sant{\textquoteright}Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy and at Luigi Sacco Hospital, University of Milan, Milan, Italy. Patients underwent complete ophthalmologic examinations, including best corrected visual acuity, intraocular pressure, anterior segment, and fundus examination. Imaging studies, including fundus color photography, near-infrared reflectance imaging, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain enhanced depth imaging optical coherence tomography were also performed. Ultra-widefield fluorescein angiography and ultra-widefield indocyanine angiography using the Heidelberg Retina Angiograph and the Staurenghi 230 SLO Retina Lens were used to demonstrate the disappearance of all retinal lesions when pressure was applied to the globe. RESULTS: All eight cases initially presented to the emergency room. One patient presented secondary to trauma, two patients presented for suspected hemangioma, whereas the other five were referred to the authors{\textquoteright} hospitals for suspected retinal lesions. On examination, retinal abnormalities were identified in all 8 patients, with 7 (87.5\%) oculus dexter and 1 (12.5\%) oculus sinister, and with 1 (12.5\%) inferotemporally, 3 (37.5\%) superonasally, 3 (37.5\%) inferonasally, and 1 (12.5\%) inferiorly. Fundus color photography showed an elevated lesion in seven patients and a nonelevated red lesion in one patient. In all patients, near-infrared reflectance imaging showed a hyporeflective lesion in the periphery of the retina. Fundus autofluorescence identified round hypofluorescent rings surrounding weakly hyperfluorescent lesions in all patients. On fluorescein angiography, all lesions were initially hyperfluorescent with a hypofluorescent ring, with the lesion becoming hyperfluorescent after injection of dye. Indocyanine green angiography demonstrated dilation of the vortex vein ampullae in all patients. Spectral-domain enhanced depth imaging optical coherence tomography demonstrated dilated choroidal vessels and a hyporeflective cavity without subretinal fluid in all patients. Ultra-widefield fluorescein angiography and ultra-widefield indocyanine angiography demonstrated disappearance of all retinal lesions when pressure was applied to the globe. Findings are consistent with the diagnosis of vortex vein varix in all eight patients, with six patients (75\%) exhibiting a single varix and two patients (25\%) exhibiting a double varix. CONCLUSION: The diagnosis of vortex vein varices can be confirmed through clinical examination through the use of digital pressure to the globe during ophthalmoscopic examination. Adjunctive multimodal imaging (fundus color photography, near-infrared reflectance imaging, fundus autofluorescence, fluorescein angiography, indocyanine angiography, and spectral-domain enhanced depth imaging optical coherence tomography) was useful in the diagnosis of vortex vein varices in the authors{\textquoteright} clinical cases. However, in more challenging clinical cases, the authors{\textquoteright} novel use of the ultra-widefield contact lens for application of ocular pressure with a resulting resolution of the varix proved to be a useful and easy diagnostic imaging method for confirming the presence of vortex vein varices.},
	keywords = {Aged, Aged, 80 and over, Child, Choroid, Female, Fluorescein Angiography, Humans, Male, Middle Aged, Multimodal Imaging, Ophthalmoscopy, Optical Imaging, Retrospective Studies, Tomography, Optical Coherence, Varicose Veins},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000575},
	author = {Veronese, Chiara and Staurenghi, Giovanni and Pellegrini, Marco and Maiolo, Chiara and Primavera, Laura and Morara, Mariachiara and Armstrong, Grayson W and Ciardella, Antonio P}
}
@article {1478323,
	title = {Multimodal ophthalmic imaging of staphylococcus aureus bacteremia associated with chorioretinitis, endocarditis, and multifocal brain abscesses},
	journal = {Am J Ophthalmol Case Rep},
	volume = {17},
	year = {2020},
	month = {2020 Mar},
	pages = {100577},
	abstract = {Purpose: bacteriemia (SAB) as critical condition for the life and occasionally involves the eyes. The aim of this report is to describe the ocular involvement with multimodal imaging. Observations: A patient admitted for evaluation of acute onset of confusion, disorientation, and generalized malaise and found to have methicillin-resistant staphylococcus aureus (MRSA)-associated endocarditis and multifocal brain abscesses was evaluated by the ophthalmology service. The patient{\textquoteright}s visual acuity was 20/20 OU without relative afferent pupillary defect and normal intraocular pressures. Bedside anterior segment examination was normal. Posterior segment examination revealed intraretinal hemorrhages and Roth spots in the posterior pole of the right eye, and two deep well-defined focal white chorioretinal infiltrates and a hemorrhagic pigment epithelium detachment in the temporal quadrant of the left eye. Multimodal imaging was utilized to document these findings and ensure adequate antibiotic therapy. Conclusion: SAB has the potential for poor visual outcomes as well as significant morbidity and mortality. Multimodal imaging of SAB-related chorioretinitis allows for accurate diagnosis as well as assessment of response to antimicrobial therapy.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2019.100577},
	author = {Veronese, Chiara and Pellegrini, Marco and Maiolo, Chiara and Morara, Mariachiara and Armstrong, Grayson W and Ciardella, Antonio P}
}
@article {1213856,
	title = {Bilateral Large Colloid Drusen in a Young Adult},
	journal = {Retina},
	volume = {37},
	number = {11},
	year = {2017},
	month = {2017 11},
	pages = {e132-e134},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001868},
	author = {Veronese, Chiara and Maiolo, Chiara and Mora, Livia D and Morara, Mariachiara and Armstrong, Grayson W and Ciardella, Antonio P}
}
@article {1511477,
	title = {New surgical approach for sutureless scleral fixation},
	journal = {Eur J Ophthalmol},
	volume = {30},
	number = {3},
	year = {2020},
	month = {2020 May},
	pages = {612-615},
	abstract = {PURPOSE: The aim of this article is to describe a novel surgical technique for sutureless scleral fixation of an intraocular lens using the newly developed FIL SSF Carlevale IOL (Soleko, Italy). METHODS: Four eyes of four patients with poor capsular support were recruited to our study, three resulting from intraocular lens subluxation and one case resulting from traumatic cataract. A novel sutureless sclera-fixated intraocular lens was implanted into the posterior chamber of each eye with sclerocorneal plugs fixating the lens to the wall of the eye. RESULTS: Mean age of patients was 52 {\textpm} 16 years, ranging from 35 to 70 years. Mean follow-up was 6.50 {\textpm} 1.29 months (range: 5-7 months). Mean preoperative best-corrected visual acuity was 0.50 {\textpm} 0.33 logMAR (range: 1-0.3 logMAR). Postoperative best-corrected visual acuity improved to 0.08 {\textpm} 0.08 logMAR (range: 0.2-0 logMAR). There was no significant change in the mean intraocular pressure and there were no postoperative complications, such as iatrogenic distortion or breakage of the intraocular lens haptic, intraocular lens decentration, endophthalmitis, or retinal detachment. DISCUSSION: To the best of our knowledge, this is the first report of outcomes using the novel sutureless sclera-fixated FIL SSF Carlevale IOL. This new surgical technique offers a simplified and effective approach for sutureless scleral intraocular lens fixation with good refractive outcomes.},
	keywords = {Adult, Aged, Female, Follow-Up Studies, Humans, Intraocular Pressure, Lens Implantation, Intraocular, Male, Middle Aged, Phacoemulsification, Pseudophakia, Retrospective Studies, Sclera, Sutureless Surgical Procedures, Visual Acuity},
	issn = {1724-6016},
	doi = {10.1177/1120672120902020},
	author = {Veronese, Chiara and Maiolo, Chiara and Armstrong, Grayson W and Primavera, Laura and Torrazza, Carlo and Della Mora, Livia and Ciardella, Antonio P}
}
@article {1347447,
	title = {Diagnostic Capability of Three-Dimensional Macular Parameters for Glaucoma Using Optical Coherence Tomography Volume Scans},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {12},
	year = {2018},
	month = {2018 Oct 01},
	pages = {4998-5010},
	abstract = {Purpose: To compare the diagnostic capability of three-dimensional (3D) macular parameters against traditional two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography. To determine if manual correction and interpolation of B-scans improve the ability of 3D macular parameters to diagnose glaucoma. Methods: A total of 101 open angle glaucoma patients (29 with early glaucoma) and 57 healthy subjects had peripapillary 2D RNFL thickness and 3D macular volume scans. Four parameters were calculated for six different-sized annuli: total macular thickness (M-thickness), total macular volume (M-volume), ganglion cell complex (GCC) thickness, and GCC volume of the innermost 3 macular layers (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer). All macular parameters were calculated with and without correction and interpolation of frames with artifacts. The areas under the receiver operating characteristic curves (AUROC) were calculated for all the parameters. Results: The 3D macular parameter with the best diagnostic performance was GCC-volume-34, with an inner diameter of 3 mm and an outer of 4 mm. The AUROC for RNFL thickness and GCC-volume-34 were statistically similar for all regions (global: RNFL thickness 0.956, GCC-volume-34 0.939, P value = 0.3827), except for the temporal GCC-volume-34, which was significantly better than temporal RNFL thickness (P value = 0.0067). Correction of artifacts did not significantly change the AUROC of macular parameters (P values between 0.8452 and 1.0000). Conclusions: The diagnostic performance of best macular parameters (GCC-volume-34 and GCC-thickness-34) were similar to or better than 2D RNFL thickness. Manual correction of artifacts with data interpolation is unnecessary in the clinical setting.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-23813},
	author = {Verticchio Vercellin, Alice C and Jassim, Firas and Poon, Linda Yi-Chieh and Tsikata, Edem and Braaf, Boy and Shah, Sneha and Ben-David, Geulah and Shieh, Eric and Lee, Ramon and Simavli, Huseyin and Que, Christian J and Papadogeorgou, Georgia and Guo, Rong and Vakoc, Benjamin J and Bouma, Brett E and de Boer, Johannes F and Chen, Teresa C}
}
@article {1661816,
	title = {Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy},
	journal = {Am J Ophthalmol},
	volume = {249},
	year = {2023},
	month = {2023 May},
	pages = {108-125},
	abstract = {PURPOSE: To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy. DESIGN: Pooled analysis of safety data from 5 clinical studies. METHODS: A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2. RESULTS: Almost all patients (95.2\%) received 9\&nbsp;{\texttimes}\&nbsp;1010 viral genomes and 87.8\% had at least 2 years of follow-up. Most patients (75.1\%) experienced at least one systemic AE, but systemic treatment-related AEs occurred in 3 patients; none were serious. Intraocular inflammation was reported in 75.6\% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflammations occurred in the anterior chamber (58.8\%) or in the vitreous (40.3\%), and were of mild (90.3\%) or moderate (8.8\%) intensity; most resolved with topical corticosteroids alone. All IOP increases were mild to moderate in intensity. No AE led to study discontinuation. Bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was comparable for patients treated bilaterally and unilaterally. CONCLUSIONS: Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.},
	keywords = {Genetic Therapy, Genetic Vectors, Humans, Inflammation, Optic Atrophy, Hereditary, Leber, Parvovirinae},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.11.026},
	author = {Vignal-Clermont, Catherine and Yu-Wai-Man, Patrick and Newman, Nancy J and Carelli, Valerio and Moster, Mark L and Biousse, Valerie and Subramanian, Prem S and Wang, An-Guor and Donahue, Sean P and Leroy, Bart P and Sadun, Alfredo A and Klopstock, Thomas and Sergott, Robert C and Rebolleda Fernandez, Gema and Chwalisz, Bart K and Banik, Rudrani and Taiel, Magali and Roux, Michel and Sahel, Jos{\'e}-Alain and LHON Study Group}
}
@article {303831,
	title = {Canonical Wnt signaling regulates extracellular matrix expression in the trabecular meshwork.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2014},
	month = {2014 Oct 28},
	abstract = {PURPOSE. Canonical Wnt signaling has emerged as a critical regulator of aqueous outflow facility and intraocular pressure (IOP). In this study, we examine the role of canonical Wnt signaling on extracellular matrix (ECM) expression in the trabecular meshwork (TM) and explore the molecular mechanisms involved. METHODS. β-catenin localization in human TM tissue was examined using immunofluorescent staining. Primary human TM cells were incubated with lithium chloride (LiCl) and the effect on active β-catenin expression was assessed by immunoblot. Adenovirus expressing a dominant-negative TCF4 mutant that lacks a β-catenin binding domain was used. Changes in the levels of the microRNA-29 (miR-29) family and ECM proteins were determined by real-time quantitative PCR and immunoblot analysis, respectively. RESULTS. β-catenin was expressed throughout the TM, with localization primarily to the plasma membrane. Incubation of TM cells with lithium chloride increased the expression of active β-catenin. Lithium chloride treatment upregulated miR-29b expression, and suppressed the levels of various ECM proteins under both basal and TGF-β2 stimulatory conditions. Infection of TM cells with a dominant-negative TCF4 mutant induced ECM levels without a significant change in the expression of the miR-29 family. CONCLUSIONS. Collectively, our data identify the canonical Wnt signaling pathway as an important modulator of ECM expression in the TM and provide a mechanistic framework for its regulation of outflow facility and IOP.},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12652},
	author = {Villarreal, Guadalupe and Chatterjee, Ayan and Oh, Sarah S and Oh, Dong-Jin and Kang, Min-Hyung and Rhee, Douglas J}
}
@article {1351209,
	title = {Pharmacological regulation of SPARC by lovastatin in human trabecular meshwork cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {3},
	year = {2014},
	month = {2014 Mar 19},
	pages = {1657-65},
	abstract = {PURPOSE: Statins have been shown to increase aqueous outflow facility. The matricellular protein SPARC (secreted protein acidic and rich in cysteine) is a critical mediator of aqueous outflow and intraocular pressure (IOP). Here, we examine the effects of lovastatin on SPARC expression in trabecular meshwork (TM) cells, exploring the molecular mechanisms involved. METHODS: Primary cultured human TM cells were incubated for 24, 48, and 72 hours with 10 μM lovastatin. In separate cultures, media was supplemented with either farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) for the duration of the 72-hour time point experiment. Trabecular meshwork cells were also pretreated for 24 hours with lovastatin followed by 24-hour stimulation with 3 ng/mL TGF-β2. Cell lysates and media were harvested and relative mRNA and protein level changes were determined. Kr{\"u}ppel-like factor 4 (KLF4) localization in normal human anterior segments was examined by immunofluorescence. Adenovirus expressing human KLF4 was used and relative changes in SPARC mRNA and protein levels were assessed. RESULTS: Incubating TM cells with lovastatin suppressed SPARC mRNA and protein levels. This effect was reversed upon media supplementation with GGPP but not FPP. Pretreating cells with lovastatin inhibited TGF-β2 induction of SPARC. The KLF4 transcription factor was expressed throughout the TM and the inner and outer walls of Schlemm{\textquoteright}s canal. Lovastatin treatment upregulated KLF4 mRNA and protein levels. Overexpression of KLF4 downregulated SPARC expression. CONCLUSIONS: Collectively, our data identify lovastatin as an important pharmacological suppressor of SPARC expression in TM cells, and provide further insight into the molecular mechanisms mediating statin enhancement of aqueous outflow facility.},
	keywords = {Adult, Aged, Cells, Cultured, Gene Expression Regulation, Glaucoma, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Immunoblotting, Lovastatin, Middle Aged, Osteonectin, Real-Time Polymerase Chain Reaction, RNA, Trabecular Meshwork},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12712},
	author = {Villarreal, Guadalupe and Chatterjee, Ayan and Oh, Sarah S and Oh, Dong-Jin and Rhee, Douglas J}
}
@article {1573109,
	title = {Anatomical and Functional Recovery Kinetics After Epiretinal Membrane Removal},
	journal = {Clin Ophthalmol},
	volume = {15},
	year = {2021},
	month = {2021},
	pages = {175-181},
	abstract = {Purpose: To investigate the nature of anatomical and functional recovery kinetics after epiretinal membrane (ERM) removal. Methods: The records of 42 patients (45 eyes) with idiopathic ERM treated with pars plana vitrectomy and surgical peeling of the ERM performed by a single surgeon at Massachusetts Eye and Ear between 2012 and 2017 were retrospectively reviewed. Outcome measures included spectral domain optical coherence tomography-measured central macular thickness (CMT) pre-operatively and at post-operative day 1, week 1, months 1, 3, 6, 12 and 24 as well as best-corrected visual acuity (BCVA). Correlations between baseline or early values and final anatomical and functional outcomes were investigated. Results: Improvement in CMT was statistically significant after 1 week, 1, 3, 6, 12 and 24 months ( \&lt; 0.01). BCVA improvement was statistically significant after 1, 6, 12 and 24 months follow-up (\&lt;0.01). The improvement of BCVA and CMT with time was found to be logarithmic (R =0.96, R =0.84) suggesting that early (\&lt;30 days) post-operative functional and anatomical changes may be predictive of long-term outcomes. Preoperative BCVA and CMT revealed a weak positive correlation with the respective BCVA and CMT at 24 months (R=0.13 and R=0.16). When plotted as a percentage of the fellow normal eye CMT, first week proportional improvement in CMT from pre-operative baseline was found to be correlated with final CMT proportional decrease (R=0.72) suggesting that first week postoperative CMT could be predictive of final CMT. Conclusion: There is a logarithmic improvement in CMT and BCVA after ERM peel with BCVA improvement following the CMT improvement. Early (less than 30 days) post-operative anatomical changes can be predictive of long-term anatomical outcomes.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S264948},
	author = {Vingopoulos, Filippos and Koulouri, Ismini and Miller, John B and Vavvas, Demetrios G}
}
@article {1653599,
	title = {Active Learning to Characterize the Full Contrast Sensitivity Function in Cataracts},
	journal = {Clin Ophthalmol},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {3109-3118},
	abstract = {Background: To characterize contrast sensitivity function (CSF) in cataractous and pseudophakic eyes compared to healthy control eyes using a novel quantitative CSF test with active learning algorithms. Methods: This is a prospective observational study at an academic medical center. CSF was measured in eyes with visually significant cataract, at least 2+ nuclear sclerosis (NS) and visual acuity (VA) >= 20/50, in pseudophakic eyes and in healthy controls with no more than 1+ NS and no visual complaints, using the Manifold Contrast Vision Meter. Outcomes included Area under the Log CSF (AULCSF) and CS thresholds at 1, 1.5, 3, 6, 12, and 18 cycles per degree (cpd). A subgroup analysis as performed on cataract eyes with VA >= 20/25. Results: A total of 167 eyes were included, 58 eyes in the cataract group, 77 controls, and 32 pseudophakic eyes with respective median AULCSF of 1.053 (0.352) vs 1.228 (0.318) vs 1.256 (0.360). In our multivariate regression model, cataract was associated with significantly reduced AULCSF (P= 0.04, β= -0.11) and contrast threshold at 6 cpd (P= 0.01, β= -0.16) compared to controls. Contrast threshold at 6 cpd was significantly reduced even in the subgroup of cataractous eyes with VA >= 20/25 (P=0.02, β=-0.16). Conclusion: The novel qCSF test detected disproportionate significant contrast deficits at 6 cpd in cataract eyes; this remained significant even in the cataractous eyes with VA >= 20/25. CSF testing may enhance cataract evaluation and surgical decision-making, particularly in patients with subjective visual complaints despite good VA.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S367490},
	author = {Vingopoulos, Filippos and Kasetty, Megan and Garg, Itika and Silverman, Rebecca F and Katz, Raviv and Vasan, Ryan A and Lorch, Alice C and Luo, Zhonghui K and Miller, John B}
}
@article {1773556,
	title = {Towards the validation of quantitative contrast sensitivity as a clinical endpoint: correlations with vision-related quality of life in bilateral AMD},
	journal = {Br J Ophthalmol},
	year = {2023},
	month = {2023 Oct 19},
	abstract = {AIM: To investigate if active learning of contrast sensitivity (CS) in bilateral age-related macular degeneration (AMD) correlates better than visual acuity (VA) with vision-related quality of life (VRQoL) using factor analysis-calibrated National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). METHODS: Prospective cross-sectional observational study in 93 patients (186 eyes) with bilateral AMD. CS was measured in one eye at a time with the quantitative CS function (qCSF) method (Adaptive Sensory Technology). Same-day VRQoL was assessed with factor analysis-calibrated NEI VFQ-25 visual function and socioemotional scales. Mixed-effects multiple linear regression analyses evaluated the associations of the qCSF outcomes and VA with the NEI VFQ-25 scales. A subgroup analysis on patients with AMD with VA more than 20/25 in both eyes was performed. RESULTS: Compared with VA, CS outcomes were associated with larger effect on both visual function scale (standardised beta coefficients (β*) for area under the logarithm of CSF (AULCSF) curve and CS thresholds at 1.5, 3 and 6 cycles per degree (cpd): β*=0.50, 0.48, 0.52, 0.46, all p\&lt;0.001, respectively, vs β*=-0.45 for VA, all p\&lt;0.001) and socioemotional scale (β* for AULCSF and CS threshold at 6 cpd: β*=0.44, 0.44 vs β*=-0.42 for VA, all p\&lt;0.001). In patients with AMD with VA more than 20/25 in both eyes (N=20), both VFQ-25 scales and all CS outcomes were significantly reduced. CONCLUSIONS: qCSF-measured CS strongly correlates with patient-reported VRQoL in bilateral AMD, even stronger than VA does. This study further validates qCSF-measured CS as a promising functional endpoint for future clinical trials in AMD.},
	issn = {1468-2079},
	doi = {10.1136/bjo-2023-323507},
	author = {Vingopoulos, Filippos and Bannerman, Augustine and Zhou, Paul and Koch, Thomas and Wescott, Hannah E and Kim, Leo and Vavvas, Demetrios and Miller, Joan W and Miller, John B}
}
@article {1635637,
	title = {Quantitative contrast sensitivity test to assess visual function in central serous chorioretinopathy},
	journal = {Br J Ophthalmol},
	volume = {107},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {1139-1143},
	abstract = {BACKGROUND: To characterise the contrast sensitivity function (CSF) in central serous chorioretinopathy (CSCR) compared with healthy controls using novel computerised contrast sensitivity (CS) testing with active learning algorithms. METHODS: Prospective observational study measuring CSF in CSCR eyes and controls using the Manifold Platform (Adaptive Sensory Technology, San Diego, California). Mixed effects multivariate regression models were used. Outcomes included area under the log CSF (AULCSF), CS thresholds at 1, 1.5, 3, 12 and 18 cycles per degree (cpd) and best-corrected visual acuity (BCVA). Associations of contrast outcomes with structural findings on optical coherence tomography (OCT) and subjective symptomatology were investigated. RESULTS: Forty CSCR eyes and 89 controls were included with median BCVA logarithm of median angle of resolution 0.10 (20/25) versus 0.00 (20/20), respectively (p=0.01). When accounting for age, CSCR was associated with significantly reduced median AULCSF (p=0.02, β=-0.14) and reduced CS thresholds at 6 cpd (p=0.009, β=-0.18), 12 cpd (p\&lt;0.001, β=-0.23) and 18 cpd (p=0.04, β=-0.09), versus controls. Within the CSCR group, subjectively perceived visual impairment (N=22) was associated with significantly decreased CS thresholds at all spatial frequencies and in AULCSF compared with asymptomatic CSCR eyes (N=18). Ellipsoid zone attenuation and subfoveal fluid on OCT were associated with decreased AULCSF and CS thresholds specifically at 3, 6 and 12 cpd, whereas presence of extrafoveal fluid at 1.5 and 3 cpd. CONCLUSION: Contrast sensitivity is significantly reduced in CSCR, and strongly correlates with subjective visual impairment. Different structural biomarkers correlate with contrast thresholds reductions at different spatial frequencies.},
	keywords = {Central Serous Chorioretinopathy, Contrast Sensitivity, Fluorescein Angiography, Humans, Retrospective Studies, Tomography, Optical Coherence, Vision Disorders, Vision, Ocular, Visual Acuity},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2021-320415},
	author = {Vingopoulos, Filippos and Garg, Itika and Lee Kim, Esther and Thomas, Merina and Silverman, Rebecca F and Kasetty, Megan and Hassan, Zakariyya Y and Yu, Gina and Joltikov, Katherine and Choi, Eun Young and La{\'\i}ns, In{\^e}s and Kim, Leo A and Zacks, David N and Miller, John B}
}
@article {1586143,
	title = {Using deep neural networks to evaluate object vision tasks in rats},
	journal = {PLoS Comput Biol},
	volume = {17},
	number = {3},
	year = {2021},
	month = {2021 Mar},
	pages = {e1008714},
	abstract = {In the last two decades rodents have been on the rise as a dominant model for visual neuroscience. This is particularly true for earlier levels of information processing, but a number of studies have suggested that also higher levels of processing such as invariant object recognition occur in rodents. Here we provide a quantitative and comprehensive assessment of this claim by comparing a wide range of rodent behavioral and neural data with convolutional deep neural networks. These networks have been shown to capture hallmark properties of information processing in primates through a succession of convolutional and fully connected layers. We find that performance on rodent object vision tasks can be captured using low to mid-level convolutional layers only, without any convincing evidence for the need of higher layers known to simulate complex object recognition in primates. Our approach also reveals surprising insights on assumptions made before, for example, that the best performing animals would be the ones using the most abstract representations-which we show to likely be incorrect. Our findings suggest a road ahead for further studies aiming at quantifying and establishing the richness of representations underlying information processing in animal models at large.},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1008714},
	author = {Vinken, Kasper and Op de Beeck, Hans}
}
@article {1806531,
	title = {Predicting Long-Term Endothelial Cell Loss after Preloaded Descemet Membrane Endothelial Keratoplasty in Fuchs{\textquoteright} Endothelial Corneal Dystrophy: A Mathematical Model},
	journal = {J Clin Med},
	volume = {13},
	number = {3},
	year = {2024},
	month = {2024 Feb 02},
	abstract = {(1) Background: This study offers a biexponential model to estimate corneal endothelial cell decay (ECD) following preloaded "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) in Fuchs{\textquoteright} endothelial corneal dystrophy (FECD) patients; (2) Methods: A total of 65 eyes undergoing DMEK alone or combined with cataract surgery were evaluated. The follow-up period was divided into an early phase (first 6 months) and a late phase (up to 36 months). Endothelial cell count (ECC) and endothelial cell loss (ECL) were analyzed; (3) Results: The half time of the ECD was 3.03 months for the early phase and 131.50 months for the late phase. The predicted time-lapse interval to reach 500 cells/mm2 was 218 months (18.17 years), while the time-lapse interval to reach 250 cells/mm2 was 349 months (29.08 years). There was no statistically significant difference between the ECL in DMEK combined with cataract extraction and DMEK alone at 24 months (p >= 0.20). At the late phase, long-term ECL prediction revealed a lower ECC half time in patients undergoing DMEK combined with cataract surgery (98.05 months) than DMEK alone (250.32 months); (4) Conclusions: Based on the mathematical modeling, a predicted average half-life of a DMEK graft could reach 18 years in FECD. Moreover, combining cataract extraction with DMEK could result in excessive ECL in the long term.},
	issn = {2077-0383},
	doi = {10.3390/jcm13030877},
	author = {Viola, Pietro and Neri, Enrico and Occhipinti, Tommaso and Parekh, Mohit and Cian, Roberto and Ponzin, Diego and Moramarco, Antonio and Iovieno, Alfonso}
}
@article {1661602,
	title = {Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty With Endothelium Inward: A 24-Month Comparative Analysis Between Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy},
	journal = {Cornea},
	volume = {42},
	number = {9},
	year = {2023},
	month = {2023 Sep 01},
	pages = {1133-1139},
	abstract = {PURPOSE: The aim of this study was to compare long-term clinical outcomes of preloaded Descemet membrane endothelial keratoplasty (DMEK) between Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK).

METHODS: In this single-center retrospective clinical case series, 71 eyes of 64 patients indicated with FECD (62\%) or BK (38\%) (with or without cataract) were treated with preloaded DMEK grafts between March 2018 and February 2020. Standard DMEK peeling, followed by manual folding of the tissue with endothelium-inward orientation and storing in a preloaded fashion inside a 2.2-mm intraocular lens cartridge. All tissues were delivered using a bimanual pull-through technique, followed by air tamponade. Graft unfolding time, endothelial cell loss, corrected distance visual acuity, central corneal thickness, rebubbling rate, and intraoperative and postoperative complications at 1, 3, 6, 12, and 24 months were recorded.

RESULTS: The mean intraoperative graft unfolding time in FECD did not differ from the BK group ( P = 0.6061). Cystoid macular edema did not differ in either group ( P = 0.6866). The rebubbling rate was found to be significantly higher in FECD compared with the BK group ( P = 0.0423). Corrected distance visual acuity significantly improved at the first month after surgery ( P = 0.0012), with no differences between FECD and BK at 24 months ( P = 0.2578). Central corneal thickness was stable postoperatively and showed no differences between the groups ( P = 0.3693). Significantly higher endothelial cell counts were observed in the FECD group at 24 months ( P = 0.0002).

CONCLUSIONS: Preloaded DMEK with "endothelium-in" offers acceptable intraoperative time, rebubbling rate, and clinical outcomes in both FECD and BK groups. Patients with FECD show better postoperative clinical outcomes even if the rebubbling rate is relatively high.},
	keywords = {Cell Count, Corneal Endothelial Cell Loss, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003138},
	author = {Viola, Pietro and Neri, Enrico and Testa, Valeria and Parekh, Mohit and Cian, Roberto and Grassetto, Andrea and Romano, Vito}
}
@article {1504078,
	title = {Swept-source optical coherence tomography imaging of the retinochoroid and beyond},
	journal = {Expert Rev Med Devices},
	volume = {17},
	number = {5},
	year = {2020},
	month = {2020 May},
	pages = {413-426},
	abstract = {: Swept-source optical coherence tomography (SS-OCT) imaging has ushered in an era of rapid and high-resolution imaging of the retinochoroid that provides detailed patho-anatomy of various layers.: In this detailed review, the technology of swept-source imaging including its principles and working has been discussed. The applications of SS-OCT in various conditions including age-related macular degeneration, diabetic retinopathy, pachychoroid spectrum of diseases, and inflammatory vitreoretinal conditions have been elaborated. For each disease, a brief review of literature along with the utility of SS-OCT and optical coherence tomography angiography has been provided with supporting figures. The advantages of SS-OCT over spectral-domain have been discussed if there is sufficient evidence in the literature. Finally, the review summarizes the technological advantages in this field of retinal imaging.: The introduction of SS-OCT in our clinics has added newer devices in our armamentarium that can provide high-quality images of the deep retina and choroid. These advances in medical devices can help in improving our knowledge relating to the pathophysiology of diseases and their evolution. In the near future, rapid and high-resolution imaging may provide real-time volumetric information of the whole retina and the choroid that can be readily used for patient care.},
	issn = {1745-2422},
	doi = {10.1080/17434440.2020.1755256},
	author = {Vira, Jayesh and Marchese, Alessandro and Singh, Rohan Bir and Agarwal, Aniruddha}
}
@article {1642386,
	title = {Histopathologic alterations in the eyelid after Hughes tarsoconjunctival flap: loss of Meibomian glands with preservation of accessory lacrimal glands},
	journal = {Orbit},
	year = {2022},
	author = {Neerukonda VK and Freitag SK and Wolkow N}
}
@article {836991,
	title = {Mitochondrial Encephalopathy and Optic Neuropathy Due to m.10158 MT-ND3 Complex I Mutation Presenting in an Adult Patient: Case Report and Review of the Literature.},
	journal = {Neurologist},
	volume = {21},
	number = {4},
	year = {2016},
	month = {2016 Jul},
	pages = {61-5},
	abstract = {INTRODUCTION: Establishing a diagnosis of mitochondrial disease in adults remains a clinician{\textquoteright}s challenge. We report a case of syndrome reminiscent of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) in an adult patient who carries m.10158T\&gt;C mutation in complex I respiratory chain gene MT-ND3 (mitochondrially encoded NADH dehydrogenase 3). CASE REPORT: This 26-year-old man from Thailand presented with new-onset headaches, seizures, stroke-like episodes, and poor vision due to optic neuropathy and cortical blindness. Instead of expected mutations in the mitochondrial tRNA gene that are frequently associated with MELAS, the mutation in MT-ND3 with variable tissue heteroplasmy (blood 5.3\%, muscle 89.5\%) was demonstrated. The patient{\textquoteright}s clinical features, blood biomarkers, neuroimaging findings, muscle biopsy with histochemical and functional in vitro analysis, and genetic studies were analyzed and compared with all previously reported ND3 disease cases. CONCLUSIONS: ND3 disease due to m.10158T\&gt;C mutation was previously described only in patients with Leigh or Leigh-like syndrome. Our findings thus indicate that ND3 disease can manifest with atypical phenotype in adults. The diagnosis of mitochondrial disease caused by other than typical MELAS-associated mutations in adults with stroke-like episodes, headaches, and seizures should be considered. An analysis of tissue other than blood, which is more likely to harbor a tissue-specific mitochondrial DNA mutation at a measurable level, may be necessary for diagnosis.},
	issn = {2331-2637},
	doi = {10.1097/NRL.0000000000000084},
	author = {Vodopivec, Ivana and Cho, Tracey A and Rizzo, Joseph F and Frosch, Matthew P and Sims, Katherine B}
}
@article {630261,
	title = {Treatment of Susac Syndrome.},
	journal = {Curr Treat Options Neurol},
	volume = {18},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {3},
	abstract = {OPINION STATEMENT: Susac syndrome is a microangiopathy of the brain, retina, and cochlea. Several lines of evidence support the concept that this disease is an acquired autoimmune disorder. Prospective, randomized, controlled studies of treatments are not available because the disease is rare. Furthermore, the average period of follow-up in reported cases is short, limiting a complete understanding of the natural history of the disease. Empirical treatment strategies are therefore based upon expert recommendations and anecdotal reports of response to various immunomodulators, and the appropriate duration of therapy is not known. In our opinion, the encephalopathic form of Susac syndrome should be treated early and aggressively to avoid cognitive dysfunction and disability. Induction therapy with pulse methylprednisolone frequently proves to be inadequate. Additional agents, including intravenous immunoglobulins, intravenous cyclophosphamide, or rituximab are often necessary to induce a sustained remission. Maintenance therapy with oral glucocorticoids combined with intravenous immunoglobulins, mycophenolate mofetil, methotrexate, azathioprine, cyclophosphamide, or rituximab is typically necessary to achieve a sustained remission. Aspirin may be used as an adjunctive agent, although evidence showing efficacy is scant. The response to treatment should be closely monitored by frequent clinical examinations, brain MRI, and fluorescein angiography. Once disease remission has been established, it appears prudent to continue maintenance treatment for at least two additional years, although the real long-term risk of future relapses remains unknown. Establishing a multicenter patient registry and biorepository is essential to study the pathogenesis of the disease, further define the duration of disease, identify reliable biomarkers that aid early diagnosis and assess risk of relapse, and develop effective disease-specific therapies.},
	issn = {1092-8480},
	doi = {10.1007/s11940-015-0386-x},
	author = {Vodopivec, Ivana and Prasad, Sashank}
}
@article {935696,
	title = {Management of Transient Monocular Vision Loss and Retinal Artery Occlusions.},
	journal = {Semin Ophthalmol},
	volume = {32},
	number = {1},
	year = {2017},
	pages = {125-133},
	abstract = {Acute transient or permanent retinal occlusive disease requires prompt medical attention and can be an ophthalmological emergency. Central retinal artery occlusion leads to permanent and severe monocular visual loss in the majority of patients. Transient monocular vision loss leaves no permanent deficits, but requires the same level of clinical vigilance, as it portends possible future adverse events, including loss of vision and stroke. Acute treatment options remain limited, and secondary prevention of cerebral ischemic events is the mainstay of management. This article reviews the current evidence for managing patients with retinal ischemia.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2016.1228417},
	author = {Vodopivec, Ivana and Cestari, Dean M and Rizzo, Joseph F}
}
@article {504046,
	title = {Clinical features, diagnostic findings, and treatment of Susac syndrome: A case series.},
	journal = {J Neurol Sci},
	volume = {357},
	number = {1-2},
	year = {2015},
	month = {2015 Oct 15},
	pages = {50-7},
	abstract = {BACKGROUND: Susac syndrome (SS) is a rare, presumed autoimmune condition characterized by the clinical triad of branch retinal artery occlusions (BRAOs), encephalopathy, and sensorineural hearing loss. The aim of this study was to evaluate clinical features, diagnostic results, treatment, and outcomes in SS. METHODS: Five patients with SS were referred to three tertiary care centers in Boston. The observation period across these patients was 7-57months. RESULTS: At initial presentation, none of the patients demonstrated the complete triad of BRAO, sensorineural hearing loss, and encephalopathy. The interval between symptom onset and diagnosis of SS was 4-30weeks. Brain MRI findings thought to be characteristic of SS (including callosal fluid-attenuated inversion recovery (FLAIR) hyperintense and T1 hypointense lesions) were frequently absent. Microinfarcts noted on diffusion-weighted imaging (DWI), BRAOs and vessel wall hyperfluorescence on fluorescein angiography (FA) were present in all cases in the acute encephalopathic phase. All patients treated with glucocorticoids and intravenous immunoglobulins (IVIg) alone experienced further clinical progression until additional immunosuppressive therapy was instituted. CONCLUSIONS: The rarity of SS, its incomplete and variable presentation, and the nonspecific imaging findings invariably led to delayed diagnosis. DWI and FA should be used to identify the acute microvascular injury and monitor treatment response. Immunomodulatory agents more potent than glucocorticoids and IVIg might be required to control the disease.},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2015.06.063},
	author = {Vodopivec, Ivana and Venna, Nagagopal and Rizzo, Joseph F and Prasad, Sashank}
}
@article {341751,
	title = {Ocular inflammation in neurorheumatic disease.},
	journal = {Semin Neurol},
	volume = {34},
	number = {4},
	year = {2014},
	month = {2014 Sep},
	pages = {444-57},
	abstract = {Neuroimmunologic and systemic rheumatic diseases are frequently accompanied by inflammation of the eye, ocular adnexa, and orbital tissues. An understanding of the diverse forms of ophthalmic pathology in these conditions aids the clinician in making appropriate preventative, diagnostic, therapeutic, and prognostic decisions. In this review, the authors address ocular inflammation in neurorheumatic disease in three sections: first, they highlight current perspectives on immune mechanisms in the development of these disorders; next, they provide a framework for the recognition and evaluation of ophthalmologic inflammatory entities; finally, they discuss in detail several inflammatory conditions that affect the nervous system and the eye, emphasizing the features that should alert neurologists to initiate ophthalmologic evaluation. The conditions discussed include multiple sclerosis, neuromyelitis optica, chronic relapsing inflammatory optic neuropathy, Susac syndrome, Cogan syndrome, acute posterior multifocal placoid pigment epitheliopathy, Vogt-Koyanagi-Harada disease, Beh{\c c}et disease, sarcoidosis, systemic lupus erythematosus, granulomatosis with polyangiitis (Wegener granulomatosis), polyarteritis nodosa, giant cell arteritis, IgG4-related disease, and Sj{\"o}gren syndrome.},
	issn = {1098-9021},
	doi = {10.1055/s-0034-1390393},
	author = {Vodopivec, Ivana and Lobo, Ann-Marie and Prasad, Sashank}
}
@article {1635663,
	title = {The impact of COVID-19 on ophthalmology resident surgical experience: a retrospective cross-sectional analysis},
	journal = {BMC Med Educ},
	volume = {22},
	number = {1},
	year = {2022},
	month = {2022 Mar 04},
	pages = {142},
	abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to in-office and surgical procedures in the field of ophthalmology. The magnitude of the impact of the pandemic on surgical training among ophthalmology residents is not known. This study aims to quantify changes in average case logs among United States (U.S.) ophthalmology residency graduates prior to and during the COVID-19 pandemic. METHODS: Retrospective, cross-sectional analysis of aggregate, national data on case logs of U.S. ophthalmology residency graduates from 2012 to 2020. The yearly\&nbsp;percent change in the average number of procedures performed in the Accreditation Council for Graduate Medical Education (ACGME) ophthalmology resident case logs were analyzed using linear regression on log-transformed dependent variables. The average percent change from 2019 to 2020 was compared to the average\&nbsp;yearly percent change from 2012 to 2019 for procedures performed as the primary surgeon, and primary surgeon and surgical assistant (S + A), as well as procedures for which there are ACGME minimum graduating numbers. RESULTS: Across all procedures and roles, average case logs in 2020 were lower than the averages in 2019. While average total cases logged as primary surgeon increased yearly by 3.2\% (95\% CI: 2.7, 3.8\%, p \&lt; 0.001) from 2012 to 2019, total primary surgeon case logs decreased by 11.2\% from 2019 to 2020. Cataract (-22.0\%) and keratorefractive (-21.1\%) surgery experienced the greatest percent decrease in average primary surgeon cases logged from 2019 to 2020. Average total cases logged as S + A experienced an average yearly increase by 1.2\% (95\% CI: 0.9,1.6\%, p \&lt; 0.001) prior to 2020, but decreased by 9.6\% from 2019 to 2020. For ACGME minimum requirements, similar changes were observed. Specifically, the average case logs in YAG, SLT, filtering (glaucoma), and intravitreal injections had been increasing significantly prior to 2020 (p \&lt; 0.05 for all) but decreased in 2020. CONCLUSIONS: These findings demonstrate the vulnerability of ophthalmology residency programs to a significant interruption in surgical volume. There is a critical need for development of competency-based, rather than volume-based, requirements to evaluate readiness for independent practice.},
	keywords = {Accreditation, Clinical Competence, COVID-19, Cross-Sectional Studies, Education, Medical, Graduate, Humans, Internship and Residency, Ophthalmology, Pandemics, Retrospective Studies, SARS-CoV-2, United States, Workload},
	issn = {1472-6920},
	doi = {10.1186/s12909-022-03205-0},
	author = {Vongsachang, Hursuong and Fliotsos, Michael J and Lorch, Alice C and Singman, Eric L and Woreta, Fasika A and Justin, Grant A}
}
@article {1709796,
	title = {Extrascleral Extension of Uveal Melanoma Along Intravitreal Needle Tracts Associated With Periodic Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration},
	journal = {JAMA Ophthalmol},
	volume = {141},
	number = {8},
	year = {2023},
	month = {2023 Aug 01},
	pages = {801-803},
	keywords = {Angiogenesis Inhibitors, Choroidal Neovascularization, Endothelial Growth Factors, Humans, Intravitreal Injections, Macular Degeneration, Ranibizumab, Retrospective Studies, Wet Macular Degeneration},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.2521},
	author = {Vongsachang, Hursuong and Stagner, Anna M and Aronow, Mary E and Wolkow, Natalie}
}
@article {1645458,
	title = {Wells Syndrome Presenting as Atypical Periorbital Cellulitis},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {38},
	number = {6},
	year = {2022},
	month = {2022 Nov-Dec 01},
	pages = {e167-e170},
	abstract = {A 62-year-old man presented with diffuse, painless, left-sided preseptal edema, erythema, and woody induration extending to the left temple. The induration generated an orbital compartment syndrome with markedly elevated intraocular pressure necessitating lateral canthotomy and cantholysis. Although atypical for an infectious etiology, empiric broad-spectrum intravenous antibiotics were initiated with no improvement. A tissue biopsy demonstrated extensive perivascular and interstitial eosinophils with focal flame figures, and the patient was diagnosed with a severe hypersensitivity reaction or eosinophilic cellulitis (Wells syndrome). The disease process remitted rapidly upon initiation of oral prednisone. Wells syndrome is a rare inflammatory eosinophilic dermatosis, most often presenting in the limbs and trunk, with few reports of facial and periorbital involvement. This case highlights the importance of considering Wells syndrome in the differential diagnosis of atypical periorbital cellulitis that is nonresponsive to antibiotics and reviews the clinicopathologic nature of this disease.},
	keywords = {Anti-Bacterial Agents, Cellulitis, Eosinophilia, Eyelid Diseases, Humans, Male, Middle Aged},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002220},
	author = {Vongsachang, Hursuong and Bleicher, Isaac D and Reshef, Edith R and Stagner, Anna M and Wolkow, Natalie}
}
@article {1490437,
	title = {Parent and Teacher Perspectives on Factors Decreasing Participation in School-Based Vision Programs},
	journal = {Ophthalmic Epidemiol},
	volume = {27},
	number = {3},
	year = {2020},
	month = {2020 Jun},
	pages = {226-236},
	abstract = {: To examine factors decreasing participation in school-based vision programs from parent and teacher perspectives.: We conducted 41 semi-structured focus groups (20 parent groups, 21 teacher/staff groups), at 10 Baltimore and 11 Chicago public elementary and middle schools offering school-based vision programs. School-based vision programs provided vision screening, eye exams, and eyeglasses if needed. Focus groups ranged in size from 2-9 participants (median\&nbsp;=\&nbsp;5). Sessions were recorded, transcribed, and coded through an iterative process to develop themes using inductive analysis.: Ninety parents and 117 teachers/staff participated. Participants identified five major factors decreasing participation in school-based vision programs: (1) challenges with the consent form, including distribution, collection, and literacy and language barriers; (2) having existing eye care; (3) misunderstandings about the program, especially related to cost and insurance; (4) difficulty raising parental awareness of the program; and (5) certain attitudes towards vision, eye care, and school-based programs, including low prioritization of eye care, mistrust of the program, fear of sharing private information, not believing their child needs glasses, and reluctance accepting {\textquoteright}subsidized{\textquoteright} services.: Parents and teachers identified important structural barriers to participation (i.e., consent form challenges and low parental awareness) and specific reasons for non-participation (i.e., attitudes, misunderstanding of the program, existing eye care) in school-based vision programs. Effective strategies are needed to facilitate return of consent forms and promote awareness of school-based vision programs among parents. Programs should also target services towards those currently without access to eye care and increase awareness about paediatric vision needs.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2020.1730910},
	author = {Vongsachang, Hursuong and Friedman, D S and Inns, A and Kretz, A M and Mukherjee, M R and Callan, J and Wahl, M and Repka, M X and Collins, M E}
}
@article {1511496,
	title = {CD4 T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy},
	journal = {Am J Pathol},
	volume = {190},
	number = {8},
	year = {2020},
	month = {2020 08},
	pages = {1723-1734},
	abstract = {Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell-mediated responses, is thought to be intricately involved, but the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that\&nbsp;continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4 T-cell infiltration into the retina. Adoptive transfer of CD4 T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-γ-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.},
	keywords = {Adoptive Transfer, Animals, CD4-Positive T-Lymphocytes, Disease Models, Animal, Disease Progression, Ischemia, Mice, Retina, Retinal Degeneration, Retinal Diseases, Retinal Ganglion Cells, Retinal Vessels},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.04.011},
	author = {Vu, Thi Hong Khanh and Chen, Huihui and Pan, Li and Cho, Kin-Sang and Doesburg, Djoeke and Thee, Eric F and Wu, Nan and Arlotti, Elisa and Jager, Martine J and Chen, Dong Feng}
}
@article {1761901,
	title = {Risk Factors for Glaucoma Diagnosis and Surgical Intervention following Pediatric Cataract Surgery in the IRIS{\textregistered} Registry},
	journal = {Ophthalmol Glaucoma},
	volume = {7},
	number = {2},
	year = {2024},
	month = {2024 Mar-Apr},
	pages = {131-138},
	abstract = {PURPOSE: To compare demographic and clinical factors associated with glaucoma following cataract surgery (GFCS) and glaucoma surgery rates between infants, toddlers, and older children using a large, ophthalmic registry. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the IRIS{\textregistered}\&nbsp;Registry (Intelligent Research in Sight) who underwent cataract surgery at <= 17 years old and between January 1, 2013 and December 31,\&nbsp;2020. METHODS: Glaucoma diagnosis and procedural codes were extracted from the electronic health records of practices participating in the IRIS Registry. Children with glaucoma diagnosis or surgery before cataract removal were excluded. The Kaplan-Meier estimator was used to determine the cumulative probability of GFCS diagnosis and glaucoma surgery after cataract surgery. Multivariable Cox regression was used to identify factors associated with GFCS and glaucoma surgery. MAIN OUTCOME MEASURES: Cumulative probability of glaucoma diagnosis and surgical intervention within 5 years after cataract surgery. RESULTS: The study included 6658 children (median age, 10.0 years; 46.2\% female). The 5-year cumulative probability of GFCS was 7.1\% (95\% confidence interval [CI], 6.1\%-8.1\%) and glaucoma surgery was 2.6\% (95\% CI, 1.9\%-3.2\%). The 5-year cumulative probability of GFCS for children aged \&lt; 1 year was 22.3\% (95\% CI, 15.7\%-28.4\%). Risk factors for GFCS included aphakia (hazard ratio [HR], 2.63; 95\% CI, 1.96-3.57), unilateral cataract (HR, 1.48; 95\% CI, 1.12-1.96), and Black race (HR, 1.61; 95\% CI, 1.12-2.32). The most common surgery was glaucoma drainage device insertion (32.6\%), followed by angle surgery (23.3\%), cyclophotocoagulation (15.1\%), and trabeculectomy (5.8\%). CONCLUSIONS: Glaucoma following cataract surgery diagnosis in children in the IRIS Registry was associated with young age, aphakia, unilateral cataract, and Black race. Glaucoma drainage device surgery was the preferred surgical treatment, consistent with the World Glaucoma Association 2013 consensus recommendations for GFCS management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Adolescent, Aphakia, Cataract, Child, Female, Follow-Up Studies, Glaucoma, Humans, Infant, Intraocular Pressure, Male, Registries, Retrospective Studies, Risk Factors, Treatment Outcome},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2023.08.009},
	author = {Vu, Daniel M and Tobias Elze and Miller, Joan W and Lorch, Alice C and VanderVeen, Deborah K and Oke, Isdin and IRIS{\textregistered} Registry Analytic Center Consortium}
}
@article {1364560,
	title = {The Immunology of Glaucoma},
	journal = {Asia Pac J Ophthalmol (Phila)},
	volume = {1},
	number = {5},
	year = {2012},
	month = {2012 Sep-Oct},
	pages = {303-11},
	abstract = {The presence of specific antibodies and T cells that are specific in patients with glaucoma supports the idea that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy, at least in some patients. At present, our understanding regarding immunological mechanisms associated with glaucomatous optic neuropathy is far from satisfactory. In this review, we examined evidence suggesting involvement of autoimmune responses in the pathogenesis of glaucoma. These include detection of autoantibodies and T cells and expression of cytokines and stress proteins in patients with glaucoma. Although immune responses are thought to be detrimental, some responses may exert a protective effect against neurodegenerative damage. Likely, the balance between positive and negative regulators determines the survival or demise of cells. It is vital that research continues to elucidate the roles of the immune system in glaucomatous neurodegeneration and the possibility of alternative modalities of treatment. These studies may also provide valuable molecular biomarkers for the diagnosis and identification of a specific cohort of patients with glaucoma, that is, those with normal-tension glaucoma.},
	issn = {2162-0989},
	doi = {10.1097/APO.0b013e31826f57a3},
	author = {Vu, T H Khanh and Jager, Martine J and Chen, Dong Feng}
}
@article {1806626,
	title = {Macula vs periphery in diabetic retinopathy: OCT-angiography and ultrawide field fluorescein angiography imaging of retinal non perfusion},
	journal = {Eye (Lond)},
	year = {2024},
	month = {2024 Feb 24},
	abstract = {OBJECTIVES: To investigate the association between peripheral non-perfusion index (NPI) on ultrawide-field fluorescein angiography (UWF-FA) and quantitative OCT-Angiography (OCT-A) metrics in the macula. METHODS: In total, 48 eyes with UWF-colour fundus photos (CFP), UWF-FA (California, Optos) and OCT-A (Spectralis, Heidelberg) were included. OCT-A (3 {\texttimes} 3 mm) was used to determine foveal avascular zone (FAZ) parameters and vessel density (VD), perfusion density (PD), fractal dimension (FD) on superficial capillary plexus (SCP). NPI{\textquoteright}s extent and distribution was determined on UWF-FA within fovea centred concentric rings corresponding to posterior pole (\&lt;10 mm), mid-periphery (10-15 mm), and far-periphery (\&gt;15 mm) and within the total retinal area, the central macular field (6{\texttimes}6 mm), ETDRS fields and within each extended ETDRS field (P3-P7). RESULTS: Macular PD was correlated to NPI in total area of retina (Spearman ρ = 0.69, p \&lt; 0.05), posterior pole (ρ = 0.48, p \&lt; 0.05), mid-periphery (ρ = 0.65, p \&lt; 0.05), far-periphery (ρ = 0.59, p \&lt; 0.05), P3-P7 (ρ = 0,55 at least, p \&lt; 0.05 for each), central macula (ρ = 0.47, p \&lt; 0.05), total area in ETDRS (ρ = 0.55, p \&lt; 0.05). Macular VD and FD were correlated to NPI of total area of the retina (ρ = 0.60 and 0.61, p \&lt; 0.05), the mid-periphery (ρ = 0.56, p \&lt; 0.05) and far-periphery (ρ = 0.60 and ρ = 0.61, p \&lt; 0.05), and in P3-P7 (p \&lt; 0.05). FAZ perimeter was significantly corelated to NPI at posterior pole and central macular area (ρ = 0.37 and 0.36, p \&lt; 0.05), and FAZ area to NPI in central macular area (ρ = 0.36, p \&lt; 0.05). CONCLUSIONS: Perfusion macular metrics on OCT-A correlated with UWF-FA{\textquoteright}s non-perfusion (NP), particularly in the retina{\textquoteright}s mid and far periphery, suggesting that OCT-A might be a useful non-invasive method to estimate peripheral retinal NP.},
	issn = {1476-5454},
	doi = {10.1038/s41433-024-02989-3},
	author = {Vujosevic, Stela and Fantaguzzi, Francesca and Silva, Paolo S and Salongcay, Recivall and Brambilla, Marco and Torti, Emanuele and Nucci, Paolo and Peto, Tunde}
}
@article {1504082,
	title = {Screening for diabetic retinopathy: new perspectives and challenges},
	journal = {Lancet Diabetes Endocrinol},
	volume = {8},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {337-347},
	abstract = {Although the prevalence of all stages of diabetic retinopathy has been declining since 1980 in populations with improved diabetes control, the crude prevalence of visual impairment and blindness caused by diabetic retinopathy worldwide increased between 1990 and 2015, largely because of the increasing prevalence of type 2 diabetes, particularly in low-income and middle-income countries. Screening for diabetic retinopathy is essential to detect referable cases that need timely full ophthalmic examination and treatment to avoid permanent visual loss. In the past few years, personalised screening intervals that take into account several risk factors have been proposed, with good cost-effectiveness ratios. However, resources for nationwide screening programmes are scarce in many countries. New technologies, such as scanning confocal ophthalmology with ultrawide field imaging and handheld mobile devices, teleophthalmology for remote grading, and artificial intelligence for automated detection and classification of diabetic retinopathy, are changing screening strategies and improving cost-effectiveness. Additionally, emerging evidence suggests that retinal imaging could be useful for identifying individuals at risk of cardiovascular disease or cognitive impairment, which could expand the role of diabetic retinopathy screening beyond the prevention of sight-threatening disease.},
	issn = {2213-8595},
	doi = {10.1016/S2213-8587(19)30411-5},
	author = {Vujosevic, Stela and Aldington, Stephen J and Silva, Paolo and Hern{\'a}ndez, Cristina and Scanlon, Peter and Peto, Tunde and Sim{\'o}, Rafael}
}
@article {382566,
	title = {A murine model for metastatic conjunctival melanoma.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2015},
	month = {2015 Feb 26},
	abstract = {Purpose: Conjunctival melanoma (CM) is an ocular malignancy with a high rate of local recurrences after treatment, and can give rise to deadly metastases. The establishment of a murine model will further our understanding of this disease and allows in vivo testing of new therapies. We therefore analyzed the ability of three CM cell lines to grow orthotopically and spread to distant sites. Furthermore, we determined the characteristics of the xenografts and their metastases. Methods: Orthotopic xenografts of human CM were established by subconjunctival injection of three different CM cell lines into NOD/SCID IL2 rγnull mice. Singe cell suspensions were generated from the primary tumors and placed subconjunctivally in another set of mice, which were then screened for metastases. The presence of melanoma markers were determined on the cell lines and during tumor development. Results: Subconjunctival injection of cultured CM cells into immunodeficient mice led to excellent subconjunctival tumor growth in all inoculated mice (n=101) within two weeks; however, no metastases were found at the time of autopsy. Serial in vivo passage of primary tumor cells resulted in metastatic tumors in the draining lymph nodes (n=21). The CM cell lines as well as the tumor xenografts and their metastases were positive for the melanoma markers HMB-45, S100B, and MART-1. Two cell lines and their corresponding xenografts carried a BRAF mutation, the third showed an NRAS mutation. Conclusions: We established a murine model for CM which shows excellent the formation of metastases in a pattern that accurately resembles metastatic human CM following in vivo passaging.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15239},
	author = {de Waard, Nadine Eunice and Cao, Jinfeng and McGuire, Sean Patrick and Kolovou, Paraskevi E and Jordanova, Ekaterina S and Ksander, Bruce R and Jager, Martine J}
}
@article {1364561,
	title = {Postoperative choroidal hemorrhage shows elevated concentration of tissue plasminogen activator},
	journal = {Retin Cases Brief Rep},
	volume = {6},
	number = {3},
	year = {2012},
	month = {2012 Summer},
	pages = {261-2},
	abstract = {PURPOSE: The purpose of this study was to report the levels of tissue plasminogen activator in liquefied suprachoroidal hemorrhage. METHODS: An interventional case report of a 61-year-old woman who underwent drainage sclerotomy for choroidal hemorrhage. RESULTS: A 61-year-old pseudophakic woman underwent pars plana vitrectomy and fluid-gas exchange for retinal detachment in her right eye and developed postoperative serous choroidal detachments with large hemorrhages. Drainage sclerotomy was performed 18 days after the initial development of suprachoroidal hemorrhage. Sample of the liquefied hemorrhage and serum sample collected during sclerotomy were tested for tissue plasminogen activator levels using the antibody tissue plasminogen activator-enzyme immunoassay test. Hemorrhage tissue plasminogen activator levels were three times the levels present in the serum. CONCLUSION: Tissue plasminogen activator may be involved in the process of suprachoroidal hemorrhage liquefaction.},
	issn = {1935-1089},
	doi = {10.1097/ICB.0b013e3182247817},
	author = {Wagley, Sushant and Yuan, Juliet and Hoffert, Deborah S and Arroyo, Jorge G}
}
@article {369031,
	title = {PERIODONTAL DISEASE AND AGE-RELATED MACULAR DEGENERATION: Results From the National Health and Nutrition Examination Survey III.},
	journal = {Retina},
	volume = {35},
	number = {5},
	year = {2015},
	month = {2015 May},
	pages = {982-8},
	abstract = {PURPOSE: To study the association between periodontal disease (PD) and age-related macular degeneration (AMD). METHODS: For this cross-sectional analysis, 8,208 adults aged 40 years or older with retinal photographs graded for AMD were used from the National Health and Nutrition Examination Survey III. National Health and Nutrition Examination Survey III standardized dental measurements of PD status (defined as loss of \&gt;3 mm of attachment between the gum and tooth in at least 10\% of sites measured). Participants were stratified into 60 years or younger and older than 60 years of age groups. Association between PD and AMD was assessed while controlling for sex, race, education, poverty income ratio, smoking, hypertension, body mass index, cardiovascular disease, and C-reactive protein. RESULTS: In this population, a total of 52.30\% had PD, and the prevalence of AMD was 11.45\%. Logistic regression model controlled for confounders and stratified by age 60 years or younger versus older than 60 years showed PD to be independently associated with an increased risk for AMD (odds ratio = 1.96, 95\% confidence interval = 1.22-3.14, P = 0.006) for those aged 60 years or younger but not for subjects older than 60 years (odds ratio = 1.32, confidence interval = 0.93-1.90, P = 0.120). CONCLUSION: In this population-based study, PD is independently associated with AMD in those aged 60 years or younger.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000427},
	author = {Wagley, Sushant and Marra, Kyle V and Salhi, Rama A and Gautam, Shiva and Campo, Rafael and Veale, Peter and Veale, John and Arroyo, Jorge G}
}
@article {1608578,
	title = {Metabolic modeling of single Th17 cells reveals regulators of autoimmunity},
	journal = {Cell},
	volume = {184},
	number = {16},
	year = {2021},
	month = {2021 Aug 05},
	pages = {4168-4185.e21},
	abstract = {Metabolism is a major regulator of immune cell function, but it remains difficult to study the metabolic status of individual cells. Here, we present Compass, an algorithm to characterize cellular metabolic states based on single-cell RNA sequencing and flux balance analysis. We applied Compass to associate metabolic states with T helper 17 (Th17) functional variability (pathogenic potential) and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known Th17/regulatory T\&nbsp;cell (Treg) differences, which we validated by metabolic assays. Compass also predicted that Th17 pathogenicity was associated with arginine and downstream polyamine metabolism. Indeed, polyamine-related enzyme expression was enhanced in pathogenic Th17 and suppressed in Treg cells. Chemical and genetic perturbation of polyamine metabolism inhibited Th17 cytokines, promoted Foxp3 expression, and remodeled the transcriptome and epigenome of Th17 cells toward a Treg-like state. In\&nbsp;vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenic T\&nbsp;cells and attenuated tissue inflammation in CNS autoimmunity.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2021.05.045},
	author = {Wagner, Allon and Wang, Chao and Fessler, Johannes and DeTomaso, David and Avila-Pacheco, Julian and Kaminski, James and Zaghouani, Sarah and Christian, Elena and Thakore, Pratiksha and Schellhaass, Brandon and Akama-Garren, Elliot and Pierce, Kerry and Singh, Vasundhara and Ron-Harel, Noga and Douglas, Vivian Paraskevi and Bod, Lloyd and Schnell, Alexandra and Puleston, Daniel and Sobel, Raymond A and Haigis, Marcia and Pearce, Erika L and Soleimani, Manoocher and Clish, Clary and Regev, Aviv and Kuchroo, Vijay K and Yosef, Nir}
}
@article {1651370,
	title = {The Effect of Sample Medication Use on Subsequent Anti-VEGF Agent Selection for Neovascular Age-Related Macular Degeneration},
	journal = {Semin Ophthalmol},
	year = {2022},
	author = {Wai, KM and Begaj, T and Patil, S and Chen, EM and Miller, JB and Kylstra, J and Aronow, M E and Young, LH and Huckfeldt, R and Husain, D and Kim, LA and Vavvas, D G and Eliott, D}
}
@article {1580490,
	title = {Contrast sensitivity function in patients with macular disease and good visual acuity},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {6},
	year = {2022},
	month = {2022 06},
	pages = {839-844},
	abstract = {INTRODUCTION: Contrast sensitivity function (CSF) may better estimate a patient{\textquoteright}s visual function compared with visual acuity (VA). Our study evaluates the quick CSF (qCSF) method to measure visual function in eyes with macular disease and good letter acuity. METHODS: Patients with maculopathies (retinal vein occlusion, macula-off retinal detachment, dry age-related macular degeneration and wet age-related macular degeneration) and good letter acuity (VA >=20/30) were included. The qCSF method uses an intelligent algorithm to measure CSF across multiple spatial frequencies. All maculopathy eyes combined and individual macular disease groups were compared with healthy control eyes. Main outcomes included area under the log CSF (AULCSF) and six CS thresholds ranging from 1 cycle per degree (cpd) to 18 cpd. RESULTS: 151 eyes with maculopathy and 93 control eyes with VA >=20/30 were included. The presence of a maculopathy was associated with significant reduction in AULCSF (β: -0.174; p\&lt;0.001) and CS thresholds at all spatial frequencies except for 18 cpd (β: -0.094 to -0.200 log CS, all p\&lt;0.01) compared with controls. Reductions in CS thresholds were most notable at low and intermediate spatial frequencies (1.5 cpd, 3 cpd and 6 cpd). CONCLUSION: CSF measured with the qCSF active learning method was found to be significantly reduced in eyes affected by macular disease despite good VA compared with healthy control eyes. The qCSF method is a promising clinical tool to quantify subtle visual deficits that may otherwise go unrecognised by current testing methods.},
	keywords = {Contrast Sensitivity, Humans, Macula Lutea, Macular Degeneration, Retinal Vein Occlusion, Visual Acuity},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-318494},
	author = {Wai, Karen M and Vingopoulos, Filippos and Garg, Itika and Kasetty, Megan and Silverman, Rebecca F and Katz, Raviv and La{\'\i}ns, In{\^e}s and Miller, Joan W and Husain, Deeba and Vavvas, Demetrios G and Kim, Leo A and Miller, John B}
}
@article {1608582,
	title = {Bacterial dacryoadenitis: clinical features, microbiology, and management of 45 cases, with a recent uptick in incidence},
	journal = {Orbit},
	volume = {41},
	number = {5},
	year = {2022},
	month = {2022 Oct},
	pages = {563-571},
	abstract = {PURPOSE: To review the clinical features, microbiology, management, and incidence of bacterial dacryoadenitis at our institution. METHODS: This was a case series examining patients with bacterial dacryoadenitis from 2004 to 2020. Charts were reviewed for demographics, comorbidities, presenting symptoms and signs, radiology, microbiology, and management. Main outcomes included need for surgical intervention or inpatient admission. RESULTS: Forty-five patients with bacterial dacryoadenitis had a mean age of 46.1\&nbsp;years. Presenting symptoms included eyelid edema (100\%), extraocular motility restriction (53.3\%), and purulent discharge (75.5\%). Based on computed tomography or magnetic resonance imaging, 9 (20.5\%) patients presented with definite abscess and 15 (34\%) presented with a phlegmon or early abscess. Eleven patients (24.4\%) required surgical drainage. Twenty patients (44.4\%) required admission, for an average stay of 4\&nbsp;days (range 2-8\&nbsp;days). Common organisms included Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. Presence of an early abscess or phlegmon correlated with need for drainage (p\&nbsp;\&lt;\&nbsp;0.01). Extraocular motility restriction correlated with need for drainage (p\&nbsp;=\&nbsp;0.02) and admission (p\&nbsp;=\&nbsp;0.05). The incidence of bacterial dacryoadenitis at our institution increased as a percentage of confirmed dacryoadenitis cases; from 2004 to 2010 the incidence was 0 to 9.1\% per year, while from 2010 to 2019 the incidence ranged from 7.7 to 36.2\%. In 2019, our institution had 17 cases (incidence 36.2\%) of bacterial dacryoadenitis. CONCLUSIONS: Bacterial dacryoadenitis is a major cause of dacryoadenitis, and its incidence may be increasing. It can resolve with minimal complications if managed appropriately, although some patients may require surgical drainage or admission for intravenous antibiotics.},
	keywords = {Abscess, Anti-Bacterial Agents, Bacteria, Cellulitis, Dacryocystitis, Humans, Incidence, Middle Aged, Retrospective Studies, Staphylococcal Infections},
	issn = {1744-5108},
	doi = {10.1080/01676830.2021.1966813},
	author = {Wai, Karen M and Locascio, Joseph J and Wolkow, Natalie}
}
@article {1789101,
	title = {Radiation-induced ophthalmic risks of long duration spaceflight: Current investigations and interventions},
	journal = {Eur J Ophthalmol},
	year = {2023},
	month = {2023 Dec 27},
	pages = {11206721231221584},
	abstract = {PURPOSE: As the average duration of space missions increases, astronauts will experience longer periods of exposure to risks of long duration space flight including microgravity and radiation. The risks from long-term exposure to space radiation remains ill-defined. We review the current literature on the possible and known risks of radiation on the eye (including radiation retinopathy) after long duration spaceflight. METHODS: A PubMed and Google Scholar search of the English language ophthalmic literature was performed from inception to July 11, 2022. The following search terms were utilized independently or in conjunction to build this manuscript: "Radiation Retinopathy", "Spaceflight", "Space Radiation", "Spaceflight Associated Neuro-Ocular Syndrome", "Microgravity", "Hypercapnia", "Radiation Shield", "Cataract", and "SANS". A concise and selective approach of references was conducted in including relevant original studies and reviews. RESULTS: A total of 65 papers were reviewed and 47 papers were included in our review. CONCLUSION: We discuss the potential and developing countermeasures to mitigate these radiation risks in preparation for future space exploration. Given the complex nature of space radiation, no single approach will fully reduce the risks of developing radiation maculopathy in long-duration spaceflight. Understanding and appropriately overcoming the risks of space radiation is key to becoming a multi-planetary species.},
	issn = {1724-6016},
	doi = {10.1177/11206721231221584},
	author = {Waisberg, Ethan and Ong, Joshua and Paladugu, Phani and Kamran, Sharif Amit and Zaman, Nasif and Tavakkoli, Alireza and Lee, Andrew G}
}
@article {1580485,
	title = {The GGLEAM Study: Understanding Glaucoma in the Ohio Amish},
	journal = {Int J Environ Res Public Health},
	volume = {18},
	number = {4},
	year = {2021},
	month = {2021 Feb 06},
	abstract = {Glaucoma leads to millions of cases of visual impairment and blindness around the world. Its susceptibility is shaped by both environmental and genetic risk factors. Although over 120 risk loci have been identified for glaucoma, a large portion of its heritability is still unexplained. Here we describe the foundation of the Genetics of GLaucoma Evaluation in the AMish (GGLEAM) study to investigate the genetic architecture of glaucoma in the Ohio Amish, which exhibits lower genetic and environmental heterogeneity compared to the general population. To date, we have enrolled 81 Amish individuals in our study from Holmes County, Ohio. As a part of our enrollment process, 62 GGLEAM study participants (42 glaucoma-affected and 20 unaffected individuals) received comprehensive eye examinations and glaucoma evaluations. Using the data from the Anabaptist Genealogy Database, we found that 80 of the GGLEAM study participants were related to one another through a large, multigenerational pedigree containing 1586 people. We plan to integrate the health and kinship data obtained for the GGLEAM study to interrogate glaucoma genetics and pathophysiology in this unique population.},
	issn = {1660-4601},
	doi = {10.3390/ijerph18041551},
	author = {Waksmunski, Andrea R and Song, Yeunjoo E and Kinzy, Tyler G and Laux, Rene{\'e} A and Sewell, Jane and Fuzzell, Denise and Fuzzell, Sarada and Miller, Sherri and Wiggs, Janey L and Pasquale, Louis R and Skarie, Jonathan M and Haines, Jonathan L and Cooke Bailey, Jessica N}
}
@article {1538350,
	title = {Interocular Difference in Retinal Nerve Fiber Layer Thickness Predicts Optic Neuritis in Pediatric-Onset Multiple Sclerosis},
	journal = {J Neuroophthalmol},
	volume = {41},
	number = {4},
	year = {2021},
	month = {2021 Dec 01},
	pages = {469-475},
	abstract = {BACKGROUND: Optical coherence tomography (OCT) is capable of quantifying retinal damage. Defining the extent of anterior visual pathway injury is important in multiple sclerosis (MS) as a way to document evidence of prior disease, including subclinical injury, and setting a baseline for patients early in the course of disease. Retinal nerve fiber layer (RNFL) thickness is typically classified as low if values fall outside of a predefined range for a healthy population. In adults, an interocular difference (IOD) in RNFL thickness greater than 5 μm identified a history of unilateral optic neuritis (ON). Through our PERCEPTION (PEdiatric Research Collaboration ExPloring Tests in Ocular Neuroimmunology) study, we explored whether RNFL IOD informs on remote ON in a multicenter pediatric-onset MS (POMS) cohort. METHODS: POMS (defined using consensus criteria and first attack \&lt;18 years) patients were recruited from 4 academic centers. A clinical history of ON (\&gt;6 months prior to an OCT scan) was confirmed by medical record review. RNFL thickness was measured on Spectralis machines (Heidelberg, Germany). Using a cohort of healthy controls from our centers tested on the same machines, RNFL thickness \&lt;86 μm (\&lt;2 SDs below the mean) was defined as abnormal. Based on previously published findings in adults, an RNFL IOD \&gt;5 μm was defined as abnormal. The proportions of POMS participants with RNFL thinning (\&lt;86 μm) and abnormal IOD (\&gt;5 μm) were calculated. Logistic regression was used to determine whether IOD was associated with remote ON. RESULTS: A total of 157 participants with POMS (mean age 15.2 years, SD 3.2; 67 [43\%] with remote ON) were enrolled. RNFL thinning occurred in 45 of 90 (50\%) ON eyes and 24 of 224 (11\%) non-ON eyes. An IOD \&gt;5 μm was associated with a history of remote ON (P \&lt; 0.001). An IOD \&gt;5 μm occurred in 62 participants, 40 (65\%) with remote ON. Among 33 participants with remote ON but normal RNFL values (>=86 μm in both eyes), 14 (42\%) were confirmed to have ON by IOD criteria (\&gt;5 μm). CONCLUSIONS: In POMS, the diagnostic yield of OCT in confirming remote ON is enhanced by considering RNFL IOD, especially for those patients with RNFL thickness for each eye in the normal range. An IOD \&gt;5 μm in patients with previous visual symptoms suggests a history of remote ON.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001070},
	author = {Waldman, Amy T and Benson, Leslie and Sollee, John R and Lavery, Amy M and Liu, Geraldine W and Green, Ari J and Waubant, Emmanuelle and Heidary, Gena and Conger, Darrel and Graves, Jennifer and Greenberg, Benjamin}
}
@article {1319487,
	title = {A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments},
	journal = {Ophthalmology},
	volume = {125},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {1961-1966},
	abstract = {PURPOSE: Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: A total of 61 premature infants with type 1 ROP. METHODS: If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. MAIN OUTCOME MEASURES: Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. RESULTS: Of 61 study eyes, 25 (41\%; 95\% confidence interval [CI], 29\%-54\%) received additional treatment: 3 (5\%; 95\% CI, 1\%-14\%) for early failure (within 4 weeks), 11 (18\%; 95\% CI, 9\%-30\%) for late recurrence of ROP (after 4 weeks), and 11 (18\%; 95\% CI, 9\%-30\%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18\%; 95\% CI, 2\%-52\%) treated with 0.25 mg, 4 of 16 eyes (25\%; 95\% CI, 7\%-52\%) treated with 0.125 mg, 8 of 24 eyes (33\%; 95\% CI, 16\%-55\%) treated with 0.063 mg, and 0 (0\%; 95\% CI, 0\%-31\%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. CONCLUSIONS: Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.05.001},
	author = {Wallace, David K and Dean, Trevano W and Hartnett, Mary Elizabeth and Kong, Lingkun and Smith, Lois E and Hubbard, G Baker and McGregor, Mary Lou and Jordan, Catherine O and Mantagos, Iason S and Bell, Edward F and Kraker, Raymond T and Pediatric Eye Disease Investigator Group}
}
@article {1062851,
	title = {Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {6},
	year = {2017},
	month = {2017 Jun 01},
	pages = {654-656},
	abstract = {Importance: Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to treat type 1 retinopathy of prematurity (ROP), but there remain concerns about systemic toxicity. A much lower dose may be effective while reducing systemic risk. Objective: To find a dose of intravitreous bevacizumab that was lower than previously used for severe ROP, was effective in this study, and could be tested in future larger studies. Design, Setting, and Participants: Between May 2015 and September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of 10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful, the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg, and finally 0.031 mg). Diluted bevacizumab was delivered using 300 {\textmu}L syringes with 5/16-inch, 30-gauge fixed needles. Interventions: Bevacizumab injections at 0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg. Main Outcomes and Measures: Success was defined as improvement in preinjection plus disease or zone I stage 3 ROP by 5 days after injection or sooner, and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results: Fifty-eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was 709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg. Conclusions and Relevance: A dose of bevacizumab as low as 0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further investigation. Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.1055},
	author = {Wallace, David K and Kraker, Raymond T and Freedman, Sharon F and Crouch, Eric R and Hutchinson, Amy K and Bhatt, Amit R and Rogers, David L and Yang, Michael B and Haider, Kathryn M and VanderVeen, Deborah K and Siatkowski, R Michael and Dean, Trevano W and Beck, Roy W and Repka, Michael X and Smith, Lois E and Good, William V and Hartnett, Mary Elizabeth and Kong, Lingkun and Holmes, Jonathan M and Pediatric Eye Disease Investigator Group (PEDIG)}
}
@article {1504088,
	title = {Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Apr 23},
	abstract = {Importance: Intravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants. Objective: To find the lowest dose of intravitreous bevacizumab effective for severe ROP. Design, Setting, and Participants: Between April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-{\textmu}L syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019. Interventions: Bevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. Main Outcomes and Measures: Success was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results: Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100\%) receiving 0.016 mg, 9 of 9 eyes (100\%) receiving 0.008 mg, 9 of 10 eyes (90\%) receiving 0.004 mg, but only 17 of 23 eyes (74\%) receiving 0.002 mg. Conclusions and Relevance: These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2020.0334},
	author = {Wallace, David K and Kraker, Raymond T and Freedman, Sharon F and Crouch, Eric R and Bhatt, Amit R and Hartnett, M Elizabeth and Yang, Michael B and Rogers, David L and Hutchinson, Amy K and VanderVeen, Deborah K and Haider, Kathryn M and Siatkowski, R Michael and Dean, Trevano W and Beck, Roy W and Repka, Michael X and Smith, Lois E and Good, William V and Kong, Lingkun and Cotter, Susan A and Holmes, Jonathan M and Pediatric Eye Disease Investigator Group (PEDIG)}
}
@article {1364562,
	title = {Image correlates of crowding in natural scenes},
	journal = {J Vis},
	volume = {12},
	number = {7},
	year = {2012},
	month = {2012 Jul 13},
	abstract = {Visual crowding is the inability to identify visible features when they are surrounded by other structure in the peripheral field. Since natural environments are replete with structure and most of our visual field is peripheral, crowding represents the primary limit on vision in the real world. However, little is known about the characteristics of crowding under natural conditions. Here we examine where crowding occurs in natural images. Observers were required to identify which of four locations contained a patch of "dead leaves{\textquoteright}{\textquoteright} (synthetic, naturalistic contour structure) embedded into natural images. Threshold size for the dead leaves patch scaled with eccentricity in a manner consistent with crowding. Reverse correlation at multiple scales was used to determine local image statistics that correlated with task performance. Stepwise model selection revealed that local RMS contrast and edge density at the site of the dead leaves patch were of primary importance in predicting the occurrence of crowding once patch size and eccentricity had been considered. The absolute magnitudes of the regression weights for RMS contrast at different spatial scales varied in a manner consistent with receptive field sizes measured in striate cortex of primate brains. Our results are consistent with crowding models that are based on spatial averaging of features in the early stages of the visual system, and allow the prediction of where crowding is likely to occur in natural images.},
	keywords = {Bayes Theorem, Crowding, Field Dependence-Independence, Fixation, Ocular, Form Perception, Humans, Logistic Models, Models, Neurological, Pattern Recognition, Visual, Photic Stimulation, Predictive Value of Tests, Space Perception, Visual Fields},
	issn = {1534-7362},
	doi = {10.1167/12.7.6},
	author = {Wallis, Thomas SA and Bex, Peter J}
}
@article {1363218,
	title = {The role of shear-induced transforming growth factor-β signaling in the endothelium},
	journal = {Arterioscler Thromb Vasc Biol},
	volume = {33},
	number = {11},
	year = {2013},
	month = {2013 Nov},
	pages = {2608-17},
	abstract = {OBJECTIVE: Vascular endothelial cells (ECs) are continuously exposed to blood flow that contributes to the maintenance of vessel structure and function; however, the effect of hemodynamic forces on transforming growth factor-β (TGF-β) signaling in the endothelium is poorly described. We examined the potential role of TGF-β signaling in mediating the protective effects of shear stress on ECs. APPROACH AND RESULTS: Human umbilical vein ECs (HUVECs) exposed to shear stress were compared with cells grown under static conditions. Signaling through the TGF-β receptor ALK5 was inhibited with SB525334. Cells were examined for morphological changes and harvested for analysis by real-time polymerase chain reaction, Western blot analysis, apoptosis, proliferation, and immunocytochemistry. Shear stress resulted in ALK5-dependent alignment of HUVECs as well as attenuation of apoptosis and proliferation compared with static controls. Shear stress led to an ALK5-dependent increase in TGF-β3 and Kr{\"u}ppel-like factor 2, phosphorylation of endothelial NO synthase, and NO release. Addition of the NO donor S-nitroso-N-acetylpenicillamine rescued the cells from apoptosis attributable to ALK5 inhibition under shear stress. Knockdown of TGF-β3, but not TGF-β1, disrupted the HUVEC monolayer and prevented the induction of Kr{\"u}ppel-like factor 2 by shear. CONCLUSIONS: Shear stress of HUVECs induces TGF-β3 signaling and subsequent activation of Kr{\"u}ppel-like factor 2 and NO, and represents a novel role for TGF-β3 in the maintenance of HUVEC homeostasis in a hemodynamic environment.},
	keywords = {Apoptosis, Endothelium, Vascular, Hemodynamics, Human Umbilical Vein Endothelial Cells, Humans, Imidazoles, Kruppel-Like Transcription Factors, Nitric Oxide, Protein-Serine-Threonine Kinases, Quinoxalines, Receptors, Transforming Growth Factor beta, RNA, Messenger, Signal Transduction, Stress, Mechanical, Transforming Growth Factor beta3},
	issn = {1524-4636},
	doi = {10.1161/ATVBAHA.113.302161},
	author = {Walshe, Tony E and Dela Paz, Nathaniel G and D{\textquoteright}Amore, Patricia A}
}
@article {1806641,
	title = {Visual search patterns during exploration of naturalistic scenes are driven by saliency cues in individuals with cerebral visual impairment},
	journal = {Sci Rep},
	volume = {14},
	number = {1},
	year = {2024},
	month = {2024 Feb 06},
	pages = {3074},
	abstract = {We investigated the relative influence of image salience and image semantics during the visual search of naturalistic scenes, comparing performance in individuals with cerebral visual impairment (CVI) and controls with neurotypical development. Participants searched for a prompted target presented as either an image or text cue. Success rate and reaction time were collected, and gaze behavior was recorded with an eye tracker. A receiver operating characteristic (ROC) analysis compared the distribution of individual gaze landings based on predictions of image salience (using Graph-Based Visual Saliency) and image semantics (using Global Vectors for Word Representations combined with Linguistic Analysis of Semantic Salience) models. CVI participants were less likely and were slower in finding the target. Their visual search behavior was also associated with a larger visual search area and greater number of fixations. ROC scores were also lower in CVI compared to controls for both model predictions. Furthermore, search strategies in the CVI group were not affected by cue type, although search times and accuracy showed a significant correlation with verbal IQ scores for text-cued searches. These results suggest that visual search patterns in CVI are driven mainly by image salience and provide further characterization of higher-order processing deficits observed in this population.},
	keywords = {Attention, Brain Diseases, Cues, Eye Movements, Fixation, Ocular, Humans, Photic Stimulation, Vision Disorders, Visual Perception},
	issn = {2045-2322},
	doi = {10.1038/s41598-024-53642-8},
	author = {Walter, Kerri and Manley, Claire E and Bex, Peter J and Merabet, Lotfi B}
}
@article {1615230,
	title = {Glaucoma following Infant Lensectomy: 2021\&thinsp;Update},
	journal = {Klin Monbl Augenheilkd},
	volume = {238},
	number = {10},
	year = {2021},
	month = {2021 Oct},
	pages = {1065-1068},
	abstract = {PURPOSE: To review information pertaining to glaucoma following infant lensectomy surgery and to provide evidence to support the responsible mechanism of this condition. METHODS AND RESULTS: Described risk factors and proposed mechanisms for infantile aphakic glaucoma were assessed. The clinical evidence observed in affected glaucoma patients was analyzed, and evidence of postoperative anterior chamber fibrosis was reviewed and interpreted. CONCLUSION: The review and assessment of laboratory and clinical evidence support the proposal that infantile aphakic glaucoma is caused, in part, by postoperative anterior chamber fibroization related to lens cell dispersion and active epithelial-mesenchymal transition with resultant filtration angle tissue injury and loss of function.},
	keywords = {Aphakia, Postcataract, Cataract, Cataract Extraction, Glaucoma, Humans, Infant, Intraocular Pressure, Retrospective Studies},
	issn = {1439-3999},
	doi = {10.1055/a-1554-5398},
	author = {Walton, David S and Yeung, Helen H}
}
@article {1363219,
	title = {Late-recognized primary congenital glaucoma},
	journal = {J Pediatr Ophthalmol Strabismus},
	volume = {50},
	number = {4},
	year = {2013},
	month = {2013 Jul-Aug},
	pages = {234-8},
	abstract = {PURPOSE: To describe a cohort of children with late-recognized primary congenital glaucoma (LRPCG), including age of presentation, age-related diagnostic signs, clinical abnormalities, and results of glaucoma surgery. METHODS: The medical records of 31 patients (49 eyes) with PCG recognized after 1 year of age were reviewed retrospectively. Patients were confirmed to have PCG based on their increased intraocular pressure (IOP), anterior segment abnormalities including findings on gonioscopy, and the absence of other causes of childhood glaucoma. The outcome of glaucoma surgery was reviewed and success measured by assessment of the relative control of IOP, occurrence of significant complications, and need for additional glaucoma surgery. RESULTS: Average age at diagnosis of glaucoma was 4.7 years (36\% diagnosed at \&gt; 4 years of age). The most common initial diagnostic signs were corneal enlargement (46\%, average age of 2.0 years), photophobia (20\%, average age of 3.3 years), and suspected poor visual acuity (32\%, average age of 9.9 years). Corneal cloudiness was not an initial sign for any patient. Haab{\textquoteright}s striae were present in 60\% of the affected 49 eyes. Gonioscopy findings were abnormal in 82\%, but the ciliary body band was seen in 81\% and the scleral spur was visible in 47\%. Sixty-one goniotomy procedures were performed for 39 eyes with overall success in 95\% (37 eyes) and complete success in 65\% (27 eyes). The final visual acuity was 20/200 or worse in 31\% (15 eyes) and 20/40 or better in 60\% (29 eyes). CONCLUSIONS: An awareness of and familiarity with the subtle diagnostic signs of LRPCG can enable its differentiation from primary juvenile glaucoma and contribute to earlier recognition and treatment. Glaucoma surgery is often required for LRPCG and goniosurgery is the recommended initial procedure.},
	keywords = {Adolescent, Anterior Eye Segment, Child, Child, Preschool, Diagnostic Techniques, Ophthalmological, Female, Humans, Hydrophthalmos, Infant, Intraocular Pressure, Male, Ophthalmologic Surgical Procedures, Retrospective Studies, Tonometry, Ocular, Visual Acuity},
	issn = {1938-2405},
	doi = {10.3928/01913913-20130423-02},
	author = {Walton, David S and Nagao, Karina and Yeung, Helen H and Kane, Steven A}
}
@article {1504070,
	title = {Use of Botulinum Toxin in Ophthalmology},
	journal = {Handb Exp Pharmacol},
	volume = {263},
	year = {2021},
	month = {2021},
	pages = {147-160},
	abstract = {Botulinum toxin is an important treatment for many conditions in ophthalmology, including strabismus, nystagmus, blepharospasm, hemifacial spasm, spastic and congenital entropion, corneal exposure, and persistent epithelial defects. The mechanism of action of botulinum toxin for both strabismus and nystagmus is the neuromuscular blockade and transient paralysis of extraocular muscles, but when botulinum toxin is used for some forms of strabismus, a single injection can convey indefinite benefits. There are two unique mechanisms of action that account for the long-term effect on ocular alignment: (1) the disruption of a balanced system of agonist-antagonist extraocular muscles and (2) the reestablishment of central control of alignment by the binocular visual system. For other ocular conditions, botulinum toxin acts through transient paralysis of periocular muscles. Botulinum toxin is a powerful tool in ophthalmology, achieving its therapeutic effects by direct neuromuscular blockade of extraocular and periocular muscles and by unique mechanisms related to the underlying structure and function of the visual system.},
	keywords = {Blepharospasm, Botulinum Toxins, Humans, Ophthalmology, Strabismus},
	issn = {0171-2004},
	doi = {10.1007/164_2019_325},
	author = {Wan, Michael J and AlShaker, Sara and Hunter, David G}
}
@article {1302167,
	title = {The Effect of Botulinum Toxin Augmentation on Strabismus Surgery for Large-Angle Infantile~Esotropia},
	journal = {Am J Ophthalmol},
	volume = {189},
	year = {2018},
	month = {2018 May},
	pages = {160-165},
	abstract = {PURPOSE: To determine whether botulinum toxin augments the effect of strabismus surgery in pediatric patients with large-angle infantile esotropia.

DESIGN: Retrospective, comparative, case series.

METHODS: Setting: Tertiary-care pediatric hospital.

STUDY POPULATION: Patients with large-angle infantile esotropia.

INTERVENTION: Treatment with botulinum toxin-augmented bilateral medial rectus muscle recessions ("augmented-surgery group") or traditional bilateral medial rectus muscle recessions ("surgery-only group").

MAIN OUTCOME MEASURE: The effect of surgery on ocular alignment at 4~months, measured in prism diopters of change per mm of surgery (PD/mm).

RESULTS: There were 14 patients in the augmented-surgery group and 16 patients in the surgery-only group. The mean effect on alignment was significantly greater in the augmented-surgery group compared to the surgery-only group at 4~months (5.7 {\textpm} 1.3 vs 4.0 {\textpm} 1.4 PD/mm, P~= .002) and at 1 year (5.4 {\textpm} 1.2 vs 3.7 {\textpm} 1.2 PD/mm, P~= .002). There was a partial loss of treatment effect between 4~months and 1 year in both groups, which was similar in magnitude (P~=~.57). On linear regression, there was a trend toward a positive correlation between botulinum toxin dose and treatment effect, but this was not statistically significant (P~= .09).

CONCLUSIONS: Botulinum toxin augments the surgical effect of medial rectus muscle recession. Botulinum toxin-augmented surgery may be an alternative to traditional options for large-angle infantile esotropia. A surgical dosing table is proposed for this technique.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.02.010},
	author = {Wan, Michael J and Gilbert, Aubrey and Kazlas, Melanie and Wu, Carolyn and Mantagos, Iason S and Hunter, David G and Shah, Ankoor S}
}
@article {1559568,
	title = {Correction to: Use of Botulinum Toxin in Ophthalmology},
	journal = {Handb Exp Pharmacol},
	volume = {263},
	year = {2021},
	month = {2021},
	pages = {283},
	issn = {0171-2004},
	doi = {10.1007/164_2020_413},
	author = {Wan, Michael J and AlShaker, Sara and Hunter, David G}
}
@article {988041,
	title = {Comparison of Botulinum Toxin With Surgery for the Treatment of Acute-Onset Comitant Esotropia in Children},
	journal = {Am J Ophthalmol},
	volume = {176},
	year = {2017},
	month = {2017 Apr},
	pages = {33-39},
	abstract = {PURPOSE: To determine whether botulinum toxin is as effective as strabismus surgery in the treatment of acute-onset comitant esotropia in children. DESIGN: Retrospective, nonrandomized, comparative clinical study. METHODS: Setting: Tertiary care pediatric hospital. STUDY POPULATION: Forty-nine children with acute-onset comitant esotropia. INTERVENTION: Treatment with either botulinum toxin ("chemodenervation group") or standard incisional strabismus surgery ("surgery group"). MAIN OUTCOME MEASURE: Success rate at 6\&nbsp;months (total horizontal deviation of 10 prism diopters or less and evidence of binocular single vision). RESULTS: There were 16 patients in the chemodenervation group and 33 patients in the surgery group. The success rate was not significantly different at 6\&nbsp;months (81\% vs 61\%, P\&nbsp;= .20) or at 18\&nbsp;months (67\% vs 58\%, P\&nbsp;= .74). The median angle of deviation and median stereoacuity were not significantly different at 6 or 18\&nbsp;months. The chemodenervation procedure was not inferior to incisional strabismus surgery at 6\&nbsp;months. The duration of general anesthesia (5 vs 71\&nbsp;min, P\&nbsp;\&lt;\&nbsp;.001) and time in the post-anesthesia care unit (37 vs 93\&nbsp;min, P \&lt; .001) were significantly shorter in the chemodenervation group. Botulinum toxin injection payment averaged $874 per procedure compared with $2783 for strabismus surgery. CONCLUSIONS: Botulinum toxin is at least as effective as surgery in the treatment of acute-onset comitant esotropia at 6\&nbsp;months while reducing the duration of general anesthesia and healthcare costs.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2016.12.024},
	author = {Wan, Michael J and Mantagos, Iason S and Shah, Ankoor S and Kazlas, Melanie and Hunter, David G}
}
@article {1435421,
	title = {Characterizing variants of unknown significance in rhodopsin: A functional genomics approach},
	journal = {Hum Mutat},
	volume = {40},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {1127-1144},
	abstract = {Characterizing the pathogenicity of DNA sequence variants of unknown significance (VUS) is a major bottleneck in human genetics, and is increasingly important in determining which patients with inherited retinal diseases could benefit from gene therapy. A library of 210 rhodopsin (RHO) variants from literature and in-house genetic diagnostic testing were created to efficiently detect pathogenic RHO variants that fail to express on the cell surface. This study, while focused on RHO, demonstrates a streamlined, generalizable method for detecting pathogenic VUS. A relatively simple next-generation sequencing-based readout was developed so that a flow cytometry-based assay could be performed simultaneously on all variants in a pooled format, without the need for barcodes or viral transduction. The resulting dataset characterized the surface expression of every RHO library variant with a high degree of reproducibility (r  = 0.92-0.95), recategorizing 37 variants. For example, three retinitis pigmentosa pedigrees were solved by identifying VUS which showed low expression levels (p.G18D, p.G101V, and p.P180T). Results were validated across multiple assays and correlated with clinical disease severity. This study presents a parallelized, higher-throughput cell-based assay for the functional characterization of VUS in RHO, and can be applied more broadly to other inherited retinal disease genes and other disorders.},
	issn = {1098-1004},
	doi = {10.1002/humu.23762},
	author = {Wan, Aliete and Place, Emily and Pierce, Eric A and Comander, Jason}
}
@article {382216,
	title = {Visual outcomes in pediatric optic neuritis},
	journal = {Am J Ophthalmol},
	volume = {158},
	number = {3},
	year = {2014},
	month = {2014 Sep},
	pages = {503-7.e2},
	abstract = {PURPOSE: To describe the visual outcomes of a large cohort of pediatric patients presenting to a tertiary care pediatric hospital with first-episode optic neuritis. DESIGN: Retrospective, observational cohort study. METHODS: In a tertiary care pediatric hospital, patients with first-episode optic neuritis and at least 3 months of follow-up over a 10-year period were assessed and followed-up in the ophthalmology department. The main outcome measures were visual acuity at 3 months and 1 year of follow-up, with analysis of risk factors for poor visual outcomes and the time course of visual recovery. RESULTS: Of the 59 pediatric patients with first-episode optic neuritis, 46 had at least 3 months of follow-up and 36 had at least 1 year of follow-up. The mean age was 12.6 years old; 72\% were female, 41\% had bilateral involvement, 52\% had or developed an underlying diagnosis (39\% multiple sclerosis, 7\% acute disseminated encephalomyelitis, 7\% neuromyelitis optica), and 91\% received treatment (85\% steroids, 7\% multimodal). At 1 year, 81\% were at least 20/20 and 89\% were at least 20/40. A poor visual outcome at 1 year (\&lt;20/40) was associated with vision of \&lt;20/20 at 3 months (P = 0.041). Other clinical characteristics, including visual acuity at presentation, sex, bilateral involvement, optic nerve edema, and underlying diagnoses were not significantly associated with poor visual outcomes. CONCLUSIONS: In this cohort of pediatric patients with optic neuritis, the majority of patients regained normal visual acuity at 1 year, regardless of baseline clinical characteristics.},
	keywords = {Adolescent, Child, Child, Preschool, Disease Progression, Female, Follow-Up Studies, Forecasting, Humans, Male, Optic Neuritis, Retrospective Studies, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.05.036},
	author = {Wan, Michael J and Adebona, Olumuyiwa and Benson, Leslie A and Gorman, Mark P and Heidary, Gena}
}
@article {341731,
	title = {Eye disorders in newborn infants (excluding retinopathy of prematurity).},
	journal = {Arch Dis Child Fetal Neonatal Ed},
	volume = {100},
	number = {3},
	year = {2015},
	month = {2015 May},
	pages = {F264-9},
	abstract = {A screening eye examination is an essential part of the newborn assessment. The detection of many ocular disorders in newborn infants can be achieved through careful observation of the infant{\textquoteright}s visual behaviour and the use of a direct ophthalmoscope to assess the ocular structures and check the red reflex. Early diagnosis and subspecialty referral can have a critical impact on the prognosis for many ocular conditions, including potentially blinding but treatable conditions such as congenital cataracts, life-threatening malignancies such as retinoblastoma and harbingers of disease elsewhere such as sporadic aniridia and its association with the development of Wilms tumour.},
	issn = {1468-2052},
	doi = {10.1136/archdischild-2014-306215},
	author = {Wan, Michael J and VanderVeen, Deborah K}
}
@article {742326,
	title = {Long-term visual outcomes of optic pathway gliomas in pediatric patients without neurofibromatosis type 1.},
	journal = {J Neurooncol},
	volume = {129},
	number = {1},
	year = {2016},
	month = {2016 Aug},
	pages = {173-8},
	abstract = {Sporadic optic pathway gliomas (OPGs) have been reported to cause more vision loss than OPGs associated with neurofibromatosis type-1, but long-term visual outcome data are limited. The purpose of this study was to report the visual outcomes of a cohort of pediatric patients with sporadic OPGs. This was a retrospective, cohort study at a tertiary care pediatric hospital and cancer institute. The study included all patients with sporadic OPGs evaluated from 1990 to 2014. The primary outcome was visual acuity at final follow-up. Secondary outcomes were risk factors for a poor visual outcome and the rate of progression. There were 59 pediatric patients included in the study. Median age at presentation was 2.5\&nbsp;years old and median follow-up was 5.2\&nbsp;years. In the worse eye at final follow-up, 16 patients (27 \%) were 20/30 or better, 9 patients (15 \%) were between 20/40 and 20/80, and 34 patients (58 \%) were 20/100 or worse. In the better eye at final follow-up, 33 patients (56 \%) were 20/30 or better, 11 patients (19 \%) were between 20/40 and 20/80, and 15 patients (25 \%) were 20/100 or worse. Risk factors for a poor visual outcome included younger age at presentation, optic nerve pallor, and tumor extent. Of the 54 patients (92 \%) who received treatment, 40 (74 \%) experienced disease progression during or after treatment. A majority of pediatric patients with sporadic OPGs had significant long-term visual impairment. In spite of treatment, tumor progression is common. Serial ophthalmic examinations with quantitative vision measurements are essential in the management of sporadic OPGs.},
	issn = {1573-7373},
	doi = {10.1007/s11060-016-2163-4},
	author = {Wan, Michael J and Ullrich, Nicole J and Manley, Peter E and Kieran, Mark W and Goumnerova, Liliana C and Heidary, Gena}
}
@article {1302170,
	title = {Long-term Surgical Outcomes for Large-angle Infantile Esotropia},
	journal = {Am J Ophthalmol},
	volume = {189},
	year = {2018},
	month = {2018 May},
	pages = {155-159},
	abstract = {PURPOSE: To report the long-term surgical outcomes for a cohort of children with large-angle infantile esotropia.

DESIGN: Multicenter, nonrandomized clinical study.

METHODS: Setting: Two tertiary-care pediatric hospitals.

STUDY POPULATION: Children with large-angle (>=55 prism diopters) infantile esotropia.

INTERVENTION: Surgical treatment of infantile esotropia.

MAIN OUTCOME MEASURE: Success rate at final follow-up (postoperative deviation <= 10 prism diopters and no need for retreatment).

RESULTS: A total of 88 patients with large-angle infantile esotropia were treated during the 13-year study period. Treatment was bilateral medial rectus muscle recessions in 70 patients, botulinum toxin-augmented surgery in 15 patients, and 3-muscle surgery in 3 patients. After a mean follow-up of 40~months, 20 patients (23\%) had a successful outcome compared to 68 treatment failures (77\%). Of the 68 treatment failures, 59 had residual or recurrent esotropia and 9 had sequential exotropia. On multivariate logistic regression, treatment modality was the only factor significantly associated with a successful outcome. Specifically, patients treated with botulinum toxin-augmented surgery were more likely to have a successful outcome compared to patients treated with bilateral medial rectus muscle recessions. For the 26 patients (30\%) who underwent retreatment, the mean number of procedures was 2.1, and 7 (27\%) had a deviation of <=10 prism diopters at final follow-up.

CONCLUSIONS: The overall success rate for treatment of large-angle infantile esotropia was poor in this cohort, with most failures owing to recurrent or residual esotropia. Botulinum toxin-augmented surgery was associated with a higher success rate at final follow-up.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.11.006},
	author = {Wan, Michael J and Chiu, Hedva and Shah, Ankoor S and Hunter, David G}
}
@article {1559535,
	title = {Stress Signal Regulation by Na/K-ATPase As a New Approach to Promote Physiological Revascularization in a Mouse Model of Ischemic Retinopathy},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {14},
	year = {2020},
	month = {2020 Dec 01},
	pages = {9},
	abstract = {Purpose: The identification of target pathways to block excessive angiogenesis while simultaneously restoring physiological vasculature is an unmet goal in the therapeutic management of ischemic retinopathies. pNaKtide, a cell-permeable peptide that we have designed by mapping the site of α1 Na/K-ATPase (NKA)/Src binding, blocks the formation of α1 NKA/Src/reactive oxygen species (ROS) amplification loops and restores physiological ROS signaling in a number of oxidative disease models. The aim of this study was to evaluate the importance of the NKA/Src/ROS amplification loop and the effect of pNaKtide in experimental ischemic retinopathy. Methods: Human retinal microvascular endothelial cells (HRMECs) and retinal pigment epithelium (ARPE-19) cells were used to evaluate the effect of pNaKtide on viability, proliferation, and angiogenesis. Retinal toxicity and distribution were assessed in those cells and in the mouse. Subsequently, the role and molecular mechanism of NKA/Src in ROS stress signaling were evaluated biochemically in the retinas of mice exposed to the well-established protocol of oxygen-induced retinopathy (OIR). Finally, pNaKtide efficacy was assessed in this model. Results: The results suggest a key role of α1 NKA in the regulation of ROS stress and the Nrf2 pathway in mouse OIR retinas. Inhibition of α1 NKA/Src by pNaKtide reduced pathologic ROS signaling and restored normal expression of hypoxia-inducible factor 1-α/vascular endothelial growth factor (VEGF). Unlike anti-VEGF agents, pNaKtide did promote retinal revascularization while inhibiting neovascularization and inflammation. Conclusions: Targeting α1 NKA represents a novel strategy to develop therapeutics that not only inhibit neovascularization but also promote physiological revascularization in ischemic eye diseases.},
	issn = {1552-5783},
	doi = {10.1167/iovs.61.14.9},
	author = {Wang, Jiayan and Wang, Xiaoliang and Gao, Yingnyu and Lin, Zhucheng and Chen, Jing and Gigantelli, James and Shapiro, Joseph I and Xie, Zijian and Pierre, Sandrine V}
}
@article {1522724,
	title = {Microglia modulation by TGF-β1 protects cones in mouse models of retinal degeneration},
	journal = {J Clin Invest},
	volume = {130},
	number = {8},
	year = {2020},
	month = {2020 Aug 03},
	pages = {4360-4369},
	abstract = {Retinitis pigmentosa (RP) is a genetically heterogenous group of eye diseases in which initial degeneration of rods triggers secondary degeneration of cones, leading to significant loss of daylight, color, and high-acuity vision. Gene complementation with adeno-associated viral (AAV) vectors is one strategy to treat RP. Its implementation faces substantial challenges, however; for example, the tremendous number of loci with causal mutations. Gene therapy targeting secondary cone degeneration is an alternative approach that could provide a much-needed generic treatment for many patients with RP. Here, we show that microglia are required for the upregulation of potentially neurotoxic inflammatory factors during cone degeneration in RP, creating conditions that might contribute to cone dysfunction and death. To ameliorate the effects of such factors, we used AAV vectors to express isoforms of the antiinflammatory cytokine transforming growth factor beta (TGF-β). AAV-mediated delivery of TGF-β1 rescued degenerating cones in 3 mouse models of RP carrying different pathogenic mutations. Treatment with TGF-β1 protected vision, as measured by 2 behavioral assays, and could be pharmacologically disrupted by either depleting microglia or blocking the TGF-β receptors. Our results suggest that TGF-β1 may be broadly beneficial for patients with cone degeneration, and potentially other forms of neurodegeneration, through a pathway dependent upon microglia.},
	issn = {1558-8238},
	doi = {10.1172/JCI136160},
	author = {Wang, Sean K and Xue, Yunlu and Cepko, Constance L}
}
@article {1538315,
	title = {Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia},
	journal = {Neuron},
	volume = {108},
	number = {5},
	year = {2020},
	month = {2020 Dec 09},
	pages = {876-886.e4},
	abstract = {Myelination facilitates rapid axonal conduction, enabling efficient communication across different parts of the nervous system. Here we examined mechanisms controlling myelination after injury and during axon regeneration in the central nervous system (CNS). Previously, we discovered multiple molecular pathways and strategies that could promote robust axon regrowth after optic nerve injury. However, regenerated axons remain unmyelinated, and the underlying mechanisms are elusive. In this study, we found that, in injured optic nerves, oligodendrocyte precursor cells (OPCs) undergo transient proliferation but fail to differentiate into mature myelination-competent oligodendrocytes, reminiscent of what is observed in human progressive multiple sclerosis. Mechanistically, we showed that OPC-intrinsic GPR17 signaling and sustained activation of microglia inhibit different stages of OPC differentiation. Importantly, co-manipulation of GPR17 and microglia led to extensive myelination of regenerated axons. The regulatory mechanisms of stage-dependent OPC differentiation uncovered here suggest a translatable strategy for efficient de novo myelination after CNS injury.},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2020.09.016},
	author = {Wang, Jing and He, Xuelian and Meng, Huyan and Li, Yi and Dmitriev, Phillip and Tian, Feng and Page, Jessica C and Lu, Q Richard and He, Zhigang}
}
@article {1498248,
	title = {Targeting Neuroinflammation in Neovascular Retinal Diseases},
	journal = {Front Pharmacol},
	volume = {11},
	year = {2020},
	month = {2020},
	pages = {234},
	abstract = {Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident microglia, retinal neurons have also been reported to contribute to inflammation, through inflammatory signals, which mediate blood vessel growth. Therefore, it is important to explore the detailed mechanisms of neuroinflammation{\textquoteright}s effects on retinal neovascularization. This review looks to summarize current research on the relationship between retinal angiogenesis and neuroinflammation in retinopathy, as well as the potential effects of neuroinflammation on retinal neovascularization in different animal models.},
	issn = {1663-9812},
	doi = {10.3389/fphar.2020.00234},
	author = {Wang, Tianxi and Tsirukis, Demetrios I and Sun, Ye}
}
@article {1125411,
	title = {A Lacrimal Gland Choristoma of the Lacrimal Sac},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2017},
	month = {2017 Jul 10},
	abstract = {Choristomatous lacrimal gland tissue has been detected in many different sites of the ocular adnexa, but has never before been convincingly described in the submucosa of the lacrimal sac. A 77-year-old woman with epiphora had a biopsy of the sac wall preformed during a dacryocystorhinostomy that contained such a lacrimal choristoma. Zymogen granules were found in the cytoplasm of the secretory cells with the periodic acid-Schiff reaction. No mucus-producing cells, as found in normal sac submucosal glands, were detected using the Alcian blue, mucicarmine, and Gomori methenamine silver histochemical stains. Gross cystic fluid protein-15 positivity was demonstrated immunohistochemically. The clinical implications of this choristoma are explored.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000953},
	author = {Wang, Yvonne and Jakobiec, Frederick A and Zakka, Fouad R and Lee, Nahyoung Grace}
}
@article {1511478,
	title = {Toxicity of the cosmetic preservatives parabens, phenoxyethanol and chlorphenesin on human meibomian gland epithelial cells},
	journal = {Exp Eye Res},
	volume = {196},
	year = {2020},
	month = {2020 Jul},
	pages = {108057},
	abstract = {Recently, we discovered that the cosmetic preservatives, benzalkonium chloride and formaldehyde, are especially toxic to human meibomian gland epithelial cells (HMGECs). Exposure to these agents, at concentrations approved for human use, leads within hours to cellular atrophy and death. We hypothesize that these effects are not unique, and that other cosmetic preservatives also exert adverse effects on HMGECs. Such compounds include parabens, phenoxyethanol and chlorphenesin, which have been reported to be toxic to corneal and conjunctival epithelial cells, the liver and kidney, as well as to irritate the eye. To test our hypothesis, we examined the influence of parabens, phenoxyethanol and chlorphenesin on the morphology, signaling, survival, proliferation and lipid expression of immortalized (I) HMGECs. These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin for up to 5 days. We monitored the signaling ability, appearance, number and neutral lipid content of the IHMGECs, as well as their lysosome accumulation. Our findings show that a 30-min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway. This effect is dose-dependent and occurs at concentrations equal to (chlorphenesin) and less than (all others) those dosages approved for human use. Further, a 24-h treatment of the IHMGECs with concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin close to, or at, the approved human dose induces cellular atrophy and death. At all concentrations tested, no preservative stimulated IHMGEC proliferation. Of particular interest, it was not possible to evaluate the influence of these preservatives, at close to human approved dosages, on IHMGEC differentiation, because the cells did not survive the treatment. In summary, our results support our hypothesis and show that methylparaben, ethylparaben, phenoxyethanol and chlorphenesin are toxic to IHMGECs.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.108057},
	author = {Wang, Jingyi and Liu, Yang and Kam, Wendy R and Li, Ying and Sullivan, David A}
}
@article {1435423,
	title = {Using Healthcare Databases to Refine Understanding of Exploratory Associations Between Drugs and Progression of Open-Angle Glaucoma},
	journal = {Clin Pharmacol Ther},
	volume = {106},
	number = {4},
	year = {2019},
	month = {2019 Oct},
	pages = {874-883},
	abstract = {We sought to refine understanding about associations identified in prior studies between angiotensin-II receptor blockers, metformin, selective serotonin reuptake inhibitors, fibric-acid derivatives, or calcium channel blockers and progression to glaucoma filtration surgery for open-angle glaucoma (OAG). We used new-initiator, active-comparator cohort designs to investigate these drugs in two data sources. We adjusted for confounders using stabilized inverse-probability-of-treatment weights and evaluated results using "intention-to-treat" and "as-treated" follow-up approaches. In both data sources, Kaplan-Meier curves showed trends for more rapid progression to glaucoma filtration surgery in patients taking calcium channel blockers compared with thiazides with as-treated (MarketScan P\&nbsp;=\&nbsp;0.15; Medicare P\&nbsp;=\&nbsp;0.03) and intention-to-treat follow-up (MarketScan P\&nbsp;\&lt;\&nbsp;0.01; Medicare P\&nbsp;=\&nbsp;0.10). There was suggestion of delayed progression for selective serotonin reuptake inhibitor compared with tricyclic antidepressants in Medicare, which was not observed in MarketScan. Our study provided support for a relationship between calcium channel blockers and OAG progression but not for other investigated drugs.},
	issn = {1532-6535},
	doi = {10.1002/cpt.1490},
	author = {Wang, Shirley V and Li, Ning and Rice, Dennis S and Grosskreutz, Cynthia L and Dryja, Thaddeus P and Prasanna, Ganesh and Lii, Joyce and Gagne, Joshua J}
}
@article {1474212,
	title = {Rationale, Design, Methodology and Baseline Data of Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT)},
	journal = {Ophthalmic Epidemiol},
	year = {2019},
	month = {2019 Nov 13},
	pages = {1-10},
	abstract = {: To describe the rationale, design, methodology and baseline characteristics of Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT), a community-based prospective cohort study in patients with type 2 diabetes mellitus (T2DM) living in northeast China.: Patients with T2DM, aged 30 years and above from communities of Fushun city, Liaoning province, China, were recruited. The presence and severity of the diabetic retinopathy (DR) were determined by a modified Early Treatment Diabetic Retinopathy Study (ETDRS) retinopathy scale of 6 fields fundus photographs. Detailed ocular examinations and questionnaires were collated, in addition to blood and urine sample collection.: Of the 2224 subjects eligible for the FS-DIRECT, 2033 (91.4\%) participated in the study. The majority of participants were female (58.9\%), the average age was 62.1 {\textpm} 9.1 years. The overall prevalence rates of DR, non-proliferative DR, proliferative DR, diabetic macular edema, and vision-threatening retinopathy were 44.3\%, 40.0\%, 4.3\%, 15.2\%, and 12.3\%, respectively. Compared to the patients without DR, patients with DR had lower income, an earlier onset of diabetes, a longer duration of diabetes, higher proportion of insulin use, higher fasting\&nbsp;plasma glucose, HbA1c, systolic blood pressure, total cholesterol and high density lipoprotein, as well as a higher level of urine protein (all \&lt; .05).: The baseline data of FS-DIRECT showed a high prevalence of DR in a community of northeast China. Further investigation will provide key information about the risk factors, impact, and trends of DR in this region.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2019.1680702},
	author = {Wang, Yu and Lin, Zhong and Wen, Liang and Rong, Shi Song and Ding, Xiao Xia and Li, Dong and Feng, Ke Mi and Wang, Feng Hua and Liang, Yuan Bo and Zhai, Gang}
}
@article {1632296,
	title = {Efficient Delivery of Adeno-Associated Virus into Inner Ear In Vivo Through Trans-Stapes Route in Adult Guinea Pig},
	journal = {Hum Gene Ther},
	volume = {33},
	number = {13-14},
	year = {2022},
	month = {2022 Jul},
	pages = {719-728},
	abstract = {Adeno-associated virus (AAV) are potent vectors to achieve treatment against hearing loss resulting from genetic defects. However, the effects of delivery routes and the corresponding transduction efficiencies for clinical applications remain elusive. In this study, we screened AAV vectors of three serotypes (AAV 8 and 9 and Anc80L65) into the inner ears of adult normal guinea pigs through trans-stapes (oval window) and trans-round window delivery routes in vivo. Trans-stapes route is akin to stape surgeries in humans. Then, auditory brainstem response (ABR) measurements were conducted to evaluate postoperative hearing, and inner ear tissues were harvested for transduction efficiency analysis. Results showed that AAV8 targeted partial inner hair cells (IHCs) in cochlear basal turn; AAV9 targeted IHCs in cochlear basal and second turn, also a part of vestibular hair cells (VHCs). In contrast, Anc80L65 contributed to green fluorescent proteins (GFP) signals of 80 - 95\% IHCs and 67 - 91\% outer hair cells (OHCs), as well as 69\% VHCs through the trans-round window route, with 15-20 decibel (dB) ABR threshold shifts. And, through the trans-stapes (oval window) route, there were 71 - 90\% IHCs and 42 - 81\% OHCs, along with 64\% VHCs demonstrating GFP positive, and the ABR threshold shifts were within 10 dB. This study revealed AAV could be efficiently delivered into mammalian inner ear cells in vivo through the trans-stapes (oval window) route with postoperative hearing preservation, and both delivery routes showed promise of virus-based clinical translation of hearing impairment treatment.},
	keywords = {Adult, Animals, Cochlea, Dependovirus, Ear, Inner, Green Fluorescent Proteins, Guinea Pigs, Hair Cells, Auditory, Inner, Hearing Loss, Humans, Mammals, Stapes, Swine},
	issn = {1557-7422},
	doi = {10.1089/hum.2021.236},
	author = {Wang, Jinghan and Zhao, Liping and Gu, Xi and Xue, Yuanyuan and Wang, Shengyi and Xiao, Ru and Vandenberghe, Luk H and Peng, Kevin A and Shu, Yilai and Li, Huawei}
}
@article {1586190,
	title = {Wide Field Swept Source Optical Coherence Tomography Angiography for the Evaluation of Proliferative Diabetic Retinopathy and Associated Lesions: A Review},
	journal = {Semin Ophthalmol},
	volume = {36},
	number = {4},
	year = {2021},
	month = {2021 May 19},
	pages = {162-167},
	abstract = {Retinal imaging remains the mainstay for monitoring and grading diabetic retinopathy. The gold standard for detecting proliferative diabetic retinopathy (PDR) requiring treatment has long been the seven-field stereoscopic fundus photography and fluorescein angiography. In the past decade, ultra-wide field fluorescein angiography (UWF-FA) has become more commonly used in clinical practice for the evaluation of more advanced diabetic retinopathy. Since its invention, optical coherence tomography (OCT) has been an important tool for the assessment of diabetic macular edema; however, OCT offered little in the assessment of neovascular changes associated with PDR until OCT-A became available. More recently, swept source OCT allowed larger field of view scans to assess a variety of DR lesions with wide field swept source optical coherence tomography (WF-SS-OCTA). This paper reviews the role of WF-SS-OCTA in detecting neovascularization of the disc (NVD), and elsewhere (NVE), microaneurysms, changes of the foveal avascular zone (FAZ), intraretinal microvascular abnormalities (IRMA), and capillary non-perfusion, as well as limitations of this evolving technology.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2021.1887901},
	author = {Wang, Marlene and Garg, Itika and Miller, John B}
}
@article {1798406,
	title = {Effector T Cells Promote Fibrosis in Corneal Transplantation Failure},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {65},
	number = {1},
	year = {2024},
	month = {2024 Jan 02},
	pages = {40},
	abstract = {PURPOSE: To evaluate whether fibrosis contributes to corneal transplant failure and to determine whether effector CD4+ T cells, the key immune cells in corneal transplant rejection, play a direct role in fibrosis formation.

METHODS: Allogeneic corneal transplantation was performed in mice. Graft opacity was evaluated by slit-lamp biomicroscopy, and fibrosis was assessed by in vivo confocal microscopy. Expression of alpha-smooth muscle actin (α-SMA) in both accepted and failed grafts was assessed by real-time PCR and immunohistochemistry. Frequencies of graft-infiltrating CD4+ T cells, neutrophils, and macrophages were assessed using flow cytometry. In vitro, MK/T-1 corneal fibroblasts were co-cultured with activated CD4+CD25- effector T cells isolated from corneal transplant recipient mice, and α-SMA expression was quantified by real-time PCR and ELISA. Neutralizing antibody was used to evaluate the role of interferon gamma (IFN-γ) in promoting α-SMA expression.

RESULTS: The majority of failed grafts demonstrated clinical signs of fibrosis which became most evident at week 6 after corneal transplantation. Failed grafts showed higher expression of α-SMA as compared to accepted grafts. Flow cytometry analysis showed a significant increase in CD4+ T cells in failed grafts compared to accepted grafts. Co-culture of activated CD4+CD25- effector T cells with corneal fibroblasts led to an increase in α-SMA expression by fibroblasts. Inhibition of IFN-γ in culture significantly suppressed this increase in α-SMA expression as compared to immunoglobulin G control.

CONCLUSIONS: Fibrosis contributes to graft opacity in corneal transplant failure and is mediated at least in part by effector CD4+ T cells via IFN-γ.},
	keywords = {Animals, Antibodies, Neutralizing, CD4-Positive T-Lymphocytes, Cornea, Corneal Diseases, Corneal Transplantation, Interferon-gamma, Mice},
	issn = {1552-5783},
	doi = {10.1167/iovs.65.1.40},
	author = {Wang, Shudan and Mittal, Sharad K and Lee, Seokjoo and Herrera, Antonio Esquivel and Krauthammer, Mark and Elbasiony, Elsayed and Blanco, Tomas and Alemi, Hamid and Nakagawa, Hayate and Chauhan, Sunil K and Dana, Reza and Dohlman, Thomas H}
}
@article {1417582,
	title = {Prosthetic Replacement of the Ocular Surface Ecosystem Treatment for Ocular Surface Disease in Pediatric Patients With Stevens-Johnson Syndrome},
	journal = {Am J Ophthalmol},
	volume = {201},
	year = {2019},
	month = {2019 May},
	pages = {1-8},
	abstract = {PURPOSE: To report the outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in pediatric patients with chronic ocular surface disease associated with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). DESIGN: Retrospective, interventional case series. METHODS: Patients aged 18 years or younger seen in consultation for PROSE treatment at a single center between January 1992 and December 2016 with a history of SJS/TEN were reviewed. Demographics, etiology of SJS/TEN, age at treatment milestones, best-corrected visual acuity (BCVA) at treatment milestones, and treatment failures were recorded. BCVA at the initial presentation visit was compared to BCVA at the time of PROSE device dispense and at the last recorded visit. RESULTS: Twenty-seven female and 22 male patients were reviewed. Reported etiology was antibiotic (n\&nbsp;= 19), antiepileptic (n\&nbsp;= 9), antipyretic (n\&nbsp;= 9), other (n\&nbsp;= 3), and unknown (n\&nbsp;= 9). The mean age was 6.4 years at disease onset and 9.3 years at time of initial presentation. The mean duration of follow-up was 5.45 years. The median BCVA at the initial presentation was 0.6 logMAR (20/80 Snellen), and was significantly improved to 0.18 logMAR (20/30 Snellen) at the time a PROSE device was dispensed (P \&lt; .0001). The median BCVA at the last recorded visit was significantly improved to 0.18 logMAR (20/30 Snellen, P\&nbsp;= .0004). There were 15 patients who failed PROSE treatment (30.6\%). CONCLUSIONS: PROSE treatment is feasible in over two thirds of pediatric patients with chronic ocular surface disease related to SJS/TEN and results in significant improvement in vision that is durable over a period of many years.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.01.006},
	author = {Wang, Yvonne and Rao, Rohini and Jacobs, Deborah S and Saeed, Hajirah N}
}
@article {1466910,
	title = {Expression of Lubricin in the Human Amniotic Membrane},
	journal = {Cornea},
	volume = {39},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {118-121},
	abstract = {PURPOSE: Lubricin, a boundary lubricant, is the body{\textquoteright}s unique antiadhesive, antifibrotic, antifriction, and antiinflammatory glycoprotein. This amphiphile is produced by numerous tissues and acts to regulate a number of processes, such as homeostasis, shear stress, tissue development, innate immunity, inflammation, and wound healing. We hypothesize that lubricin is also synthesized and expressed by the amniotic membrane (AM), which also possesses antiadhesive, antifibrotic, and antiinflammatory properties. We also hypothesize that lubricin, at least in part, mediates these AM capabilities. Our goal was to test our hypothesis. METHODS: We obtained multiple samples of fresh, cryopreserved (CP), and freeze-dried (FD) human AMs, as well as fresh placental tissue as positive controls, and processed them for light microscopy, immunofluorescence, and western blot analyses. We also evaluated the ability of recombinant human lubricin to associate with FD-AMs. RESULTS: Our results demonstrate that all fresh placental, fresh AM, and CP-AM samples contained lubricin. Lubricin was expressed in placental chorionic villi, AM epithelial and stromal cells, and CP-AM epithelia. No lubricin could be detected in FD-AMs but could be restored in FD-AMs after overnight incubation with recombinant human lubricin. CONCLUSIONS: This study supports our hypothesis that lubricin is expressed in human AMs. In addition, our data show that preservation methods influence the extent of this expression. Indeed, the disappearance of lubricin in FD-AMs may explain why dried AM reportedly loses its antiinflammatory and antiscarring abilities. It is possible that lubricin may mediate, at least in part, many of the biological properties of AMs.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002151},
	author = {Wang, Jingyi and Chen, Di and Sullivan, David A and Xie, Huatao and Li, Ying and Liu, Yang}
}
@article {1307465,
	title = {Reversal of Glaucoma Hemifield Test Results and Visual Field Features in Glaucoma},
	journal = {Ophthalmology},
	volume = {125},
	number = {3},
	year = {2018},
	month = {2018 Mar},
	pages = {352-360},
	abstract = {PURPOSE: To develop a visual field (VF) feature model to predict the reversal of glaucoma hemifield test (GHT) results to within normal limits (WNL) after 2 consecutive outside normal limits (ONL) results. DESIGN: Retrospective cohort study. PARTICIPANTS: Visual fields of 44 503 eyes from 26 130 participants. METHODS: Eyes with 3 or more consecutive reliable VFs measured with the Humphrey Field Analyzer (Swedish interactive threshold algorithm standard 24-2) were included. Eyes with ONL GHT results for the 2 baseline VFs were selected. We extracted 3 categories of VF features from the baseline tests: (1) VF global indices (mean deviation [MD] and pattern standard deviation), (2) mismatch between baseline VFs, and (3) VF loss patterns (archetypes). Logistic regression was applied to predict the GHT results reversal. Cross-validation was applied to evaluate the model on testing data by the area under the receiver operating characteristic curve (AUC). We ascertained clinical glaucoma status on a patient subset (n\&nbsp;= 97) to determine the usefulness of our model. MAIN OUTCOME MEASURES: Predictive models for GHT results reversal using VF features. RESULTS: For the 16 604 eyes with 2 initial ONL results, the prevalence of a subsequent WNL result increased from 0.1\% for MD \&lt;\&nbsp;-12 dB to 13.8\% for MD >=-3 dB. Compared with models with VF global indices, the AUC of predictive models increased from 0.669 (MD >=-3 dB) and 0.697 (-6 dB <= MD \&lt;\&nbsp;-3 dB) to 0.770 and 0.820, respectively, by adding VF mismatch features and computationally derived VF archetypes (P \&lt; 0.001 for both). The GHT results reversal was associated with a large mismatch between baseline VFs. Moreover, the GHT results reversal was associated more with VF archetypes of nonglaucomatous loss, severe widespread loss, and lens rim artifacts. For a subset of 97 eyes, using our model to predict absence of glaucoma based on clinical evidence after 2 ONL results yielded significantly better prediction accuracy (87.7\%; P \&lt; 0.001) than predicting GHT results reversal (68.8\%) with a prescribed specificity 67.7\%. CONCLUSIONS: Using VF features may predict the GHT results reversal to WNL after 2 consecutive ONL results.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2017.09.021},
	author = {Wang, Mengyu and Pasquale, Louis R and Shen, Lucy Q and Boland, Michael V and Wellik, Sarah R and De Moraes, Carlos Gustavo and Myers, Jonathan S and Wang, Hui and Baniasadi, Neda and Li, Dian and Silva, Rafaella Nascimento E and Bex, Peter J and Tobias Elze}
}
@article {1635629,
	title = {Contact Lenses for Ocular Surface Disease},
	journal = {Eye Contact Lens},
	volume = {48},
	number = {3},
	year = {2022},
	month = {2022 Mar 01},
	pages = {115-118},
	abstract = {ABSTRACT: Ocular surface disease can be difficult to manage, causing patients discomfort and vision loss. Therapeutic contact lenses are an important treatment option that is often neglected because it is conventional wisdom that eyes that are dry or irritated are not good candidates for contact lens. In this focused review, we consider the substantial literature on the use of bandage soft contact lenses (BSCL), scleral lenses, and customized prosthetic devices in the management of ocular graft-vs-host disease. Reports on BSCLs for recurrent corneal erosion are reviewed, as is literature on scleral lenses and prosthetic replacement of the ocular surface ecosystem treatment for Stevens-Johnson syndrome. Clinical pearls for fitting BSCLs are presented, and the issue of antibiotic prophylaxis is considered.},
	keywords = {Contact Lenses, Hydrophilic, Corneal Diseases, Ecosystem, Humans, Retrospective Studies, Sclera, Vision Disorders, Visual Acuity},
	issn = {1542-233X},
	doi = {10.1097/ICL.0000000000000879},
	author = {Wang, Xueyang and Jacobs, Deborah S}
}
@article {280831,
	title = {Common and Rare Genetic Risk Factors for Glaucoma.},
	journal = {Cold Spring Harb Perspect Med},
	year = {2014},
	month = {2014 Sep 18},
	abstract = {The characterization of genes responsible for glaucoma is the critical first step toward the development of gene-based diagnostic and screening tests, which could identify individuals at risk for disease before irreversible optic nerve damage occurs. Early-onset forms of glaucoma affecting children and young adults are typically inherited as Mendelian autosomal dominant or recessive traits whereas glaucoma affecting older adults has complex inheritance. In this report, we present a comprehensive overview of the genes and genomic regions contributing to inherited glaucoma.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a017244},
	author = {Wang, Ryan and Wiggs, Janey L}
}
@article {1647881,
	title = {Role of therapeutic contact lenses in management of corneal disease},
	journal = {Curr Opin Ophthalmol},
	volume = {33},
	number = {4},
	year = {2022},
	month = {2022 Jul 01},
	pages = {306-310},
	abstract = {PURPOSE OF REVIEW: The current review highlights areas of innovation and research in the use of contact lenses in the treatment of corneal ectasia and ocular surface disease. RECENT FINDINGS: A series of academic reports were published by a committee of experts reviewing evidence-based practice patterns of contact lens use. There continues to be active research in the use of contact lenses in the management of keratoconus, including mini-scleral lenses, custom impression-based scleral lenses and wavefront-guided scleral lenses. Recent reports on contact lenses for ocular surface disease were primarily reviews, retrospective case reports or case series, with publications on contact lens use in corneal epithelial defects, graft-vs.-host disease, limbal stem cell deficiency and neurotrophic keratitis. There are recent publications on advances in drug-eluting contact lenses. SUMMARY: Corneal specialists should be aware of current advances in the field of contact lens expanding their use in corneal ectasia and ocular surface disease.},
	keywords = {Contact Lenses, Hydrophilic, Dilatation, Pathologic, Humans, Keratoconus, Retrospective Studies, Sclera},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000859},
	author = {Wang, Yvonne and Jacobs, Deborah S}
}
@article {1282156,
	title = {Dynamic gaze-position prediction of saccadic eye movements using a Taylor series},
	journal = {J Vis},
	volume = {17},
	number = {14},
	year = {2017},
	month = {2017 Dec 01},
	pages = {3},
	abstract = {Gaze-contingent displays have been widely used in vision research and virtual reality applications. Due to data transmission, image processing, and display preparation, the time delay between the eye tracker and the monitor update may lead to a misalignment between the eye position and the image manipulation during eye movements. We propose a method to reduce the misalignment using a Taylor series to predict the saccadic eye movement. The proposed method was evaluated using two large datasets including 219,335 human saccades (collected with an EyeLink 1000 system, 95\% range from 1{\textdegree} to 32{\textdegree}) and 21,844 monkey saccades (collected with a scleral search coil, 95\% range from 1{\textdegree} to 9{\textdegree}). When assuming a 10-ms time delay, the prediction of saccade movements using the proposed method could reduce the misalignment greater than the state-of-the-art methods. The average error was about 0.93{\textdegree} for human saccades and 0.26{\textdegree} for monkey saccades. Our results suggest that this proposed saccade prediction method will create more accurate gaze-contingent displays.},
	issn = {1534-7362},
	doi = {10.1167/17.14.3},
	author = {Wang, Shuhang and Woods, Russell L and Costela, Francisco M and Luo, Gang}
}
@article {1302178,
	title = {Acute transient large-angle exotropia caused by traumatic orbital contusion},
	journal = {Orbit},
	year = {2018},
	month = {2018 Feb 26},
	pages = {1-3},
	abstract = {We report an unusual case of acute large-angle left exotropia associated with blunt orbital trauma in a healthy 8-year-old boy. Examination revealed a large-angle left exotropia with limitation in adduction of the left eye. Microhyphema and commotio retinae of the left eye were also present. High-resolution orbital magnetic resonance imaging (MRI) demonstrated perimuscular and intramuscular edema mostly involving the left medial rectus muscle but also involving the left lateral rectus muscle. The extraocular muscle insertions were intact. Complete resolution of the strabismus and adduction limitation occurred within 24\&nbsp;hours of starting systemic steroid therapy. This case highlights the utility of high-resolution imaging to assess for injury to the extraocular muscles. If disinsertion, transection, or rupture of the muscle is not present on imaging, resolution may occur with systemic steroid therapy and surgical intervention is not needed.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2018.1435696},
	author = {Wang, Jay C and Elliott, Alexandra T}
}
@article {280896,
	title = {A gene regulatory network controls the binary fate decision of rod and bipolar cells in the vertebrate retina},
	journal = {Dev Cell},
	volume = {30},
	number = {5},
	year = {2014},
	month = {2014 Sep 08},
	pages = {513-27},
	abstract = {Gene regulatory networks (GRNs) regulate critical events during development. In complex tissues, such as the mammalian central nervous system (CNS), networks likely provide the complex regulatory interactions needed to direct the specification of the many CNS cell types. Here, we dissect a GRN that regulates a binary fate decision between two siblings in the murine retina, the rod photoreceptor and bipolar interneuron. The GRN centers on Blimp1, one of the transcription factors (TFs) that regulates the rod versus bipolar cell fate decision. We identified a cis-regulatory module (CRM), B108, that mimics Blimp1 expression. Deletion of genomic B108 by CRISPR/Cas9 in vivo using electroporation abolished the function of Blimp1. Otx2 and RORβ were found to regulate Blimp1 expression via B108, and Blimp1 and Otx2 were shown to form a negative feedback loop that regulates the level of Otx2, which regulates the production of the correct ratio of rods and bipolar cells.},
	keywords = {Animals, Cell Differentiation, Cell Lineage, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Homeodomain Proteins, In Situ Hybridization, Fluorescence, Mice, Nuclear Receptor Subfamily 1, Group F, Member 2, Otx Transcription Factors, Positive Regulatory Domain I-Binding Factor 1, Receptor, Notch1, Retina, Retinal Bipolar Cells, Retinal Rod Photoreceptor Cells, Transcription Factors},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2014.07.018},
	author = {Wang, Sui and Sengel, Cem and Emerson, Mark M and Cepko, Constance L}
}
@article {1137921,
	title = {Single stranded adeno-associated virus achieves efficient gene transfer to anterior segment in the mouse eye},
	journal = {PLoS One},
	volume = {12},
	number = {8},
	year = {2017},
	month = {2017},
	pages = {e0182473},
	abstract = {Adeno-associated viruses (AAVs) are used extensively as a gene delivery vehicle for retinal gene therapy, yet its ability to target the anterior segment of the eye, critical to unlocking therapeutic opportunities, is less characterized. Previously, self-complimentary (sc) AAV was shown to be necessary for transduction of the cornea and trabecular meshwork (TM), limiting the size of the gene transfer cassette, likely due to a block in second strand synthesis thought to be required for functional transduction. Here, we evaluated several AAV capsids in a single stranded (ss) genome conformation for their ability to overcome the need for scAAV for targeting corneal endothelium and TM. AAV2, 8, and a recently synthetically developed AAV called Anc80L65 were evaluated in vitro and in vivo by intracameral injection in mice. Results show that although scAAV2 demonstrated superior infectivity in vitro including Human Trabecular meshwork (HTM) immortalized cell lines; Anc80L65 transduced following a single intracameral injection efficiently all components of the mouse anterior segment, including the TM, corneal stroma, and endothelial cells. These results suggest that Anc80L65 is able to overcome the requirement for scAAV genomes to enable TM and corneal targeting, expanding the potential experimental and therapeutic use of AAV gene transfer in the anterior segment of the eye.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0182473},
	author = {Wang, Li and Xiao, Ru and Andres-Mateos, Eva and Vandenberghe, Luk H}
}
@article {1078831,
	title = {Habitual coffee consumption and genetic predisposition to obesity: gene-diet interaction analyses in three US prospective studies},
	journal = {BMC Med},
	volume = {15},
	number = {1},
	year = {2017},
	month = {2017 May 09},
	pages = {97},
	abstract = {BACKGROUND: Whether habitual coffee consumption interacts with the genetic predisposition to obesity in relation to body mass index (BMI) and obesity is unknown. METHODS: We analyzed the interactions between genetic predisposition and habitual coffee consumption in relation to BMI and obesity risk in 5116 men from the Health Professionals Follow-up Study (HPFS), in 9841 women from the Nurses{\textquoteright} Health Study (NHS), and in 5648 women from the Women{\textquoteright}s Health Initiative (WHI). The genetic risk score was calculated based on 77 BMI-associated loci. Coffee consumption was examined prospectively in relation to BMI. RESULTS: The genetic association with BMI was attenuated among participants with higher consumption of coffee than among those with lower consumption in the HPFS (P interaction  = 0.023) and NHS (P interaction  = 0.039); similar results were replicated in the WHI (P interaction  = 0.044). In the combined data of all cohorts, differences in BMI per increment of 10-risk allele were 1.38 (standard error (SE), 0.28), 1.02 (SE, 0.10), and 0.95 (SE, 0.12) kg/m(2) for coffee consumption of \&lt; 1, 1-3 and \&gt; 3 cup(s)/day, respectively (P interaction  \&lt; 0.001). Such interaction was partly due to slightly higher BMI with higher coffee consumption among participants at lower genetic risk and slightly lower BMI with higher coffee consumption among those at higher genetic risk. Each increment of 10-risk allele was associated with 78\% (95\% confidence interval (CI), 59-99\%), 48\% (95\% CI, 36-62\%), and 43\% (95\% CI, 28-59\%) increased risk for obesity across these subgroups of coffee consumption (P interaction  = 0.008). From another perspective, differences in BMI per increment of 1 cup/day coffee consumption were 0.02 (SE, 0.09), -0.02 (SE, 0.04), and -0.14 (SE, 0.04) kg/m(2) across tertiles of the genetic risk score. CONCLUSIONS: Higher coffee consumption might attenuate the genetic associations with BMI and obesity risk, and individuals with greater genetic predisposition to obesity appeared to have lower BMI associated with higher coffee consumption.},
	issn = {1741-7015},
	doi = {10.1186/s12916-017-0862-0},
	author = {Wang, Tiange and Huang, Tao and Kang, Jae H and Zheng, Yan and Jensen, Majken K and Wiggs, Janey L and Pasquale, Louis R and Fuchs, Charles S and Campos, Hannia and Rimm, Eric B and Willett, Walter C and Hu, Frank B and Qi, Lu}
}
@article {1402590,
	title = {Wnt Signaling in vascular eye diseases},
	journal = {Prog Retin Eye Res},
	year = {2018},
	month = {2018 Dec 01},
	abstract = {The Wnt signaling pathway plays a pivotal role in vascular morphogenesis in various organs including the eye. Wnt ligands and receptors are key regulators of ocular angiogenesis both during the eye development and in vascular eye diseases. Wnt signaling participates in regulating multiple vascular beds in the eye including regression of the hyaloid vessels, and development of structured layers of vasculature in the retina. Loss-of-function mutations in Wnt signaling components cause rare genetic eye diseases in humans such as Norrie disease, and familial exudative vitreoretinopathy (FEVR) with defective ocular vasculature. On the other hand, experimental studies in more prevalent vascular eye diseases, such as wet age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), and corneal neovascularization, suggest that aberrantly increased Wnt signaling is one of the causations for pathological ocular neovascularization, indicating the potential of modulating Wnt signaling to ameliorate pathological angiogenesis in eye diseases. This review recapitulates the key roles of the Wnt signaling pathway during ocular vascular development and in vascular eye diseases, and pharmaceutical approaches targeting the Wnt signaling as potential treatment options.},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2018.11.008},
	author = {Wang, Zhongxiao and Liu, Chi-Hsiu and Huang, Shuo and Chen, Jing}
}
@article {1490455,
	title = {MULTIMODAL IMAGING IN ACUTE RETINAL NECROSIS PRESENTING WITH MACULAR INVOLVEMENT},
	journal = {Retin Cases Brief Rep},
	volume = {16},
	number = {3},
	year = {2022},
	month = {2022 May 01},
	pages = {347-350},
	abstract = {PURPOSE: To report an unusual case of early macular necrosis in acute retinal necrosis and its features on multimodal imaging. METHODS: Findings on fundus examination, laboratory workup, fluorescein angiography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 31-year-old healthy woman presented with 1 week of photophobia and central scotoma of the right eye. Initial examination revealed vitritis, hyperemia of the optic disc, and a yellow-white macular lesion without any peripheral findings. Peripheral involvement was first noted only 4 days later. The patient was diagnosed with acute retinal necrosis secondary to varicella zoster virus and was successfully treated with intravitreal and oral antiviral medications. Optical coherence tomography imaging of the macular lesion showed involvement of both the inner and outer retina. Optical coherence tomography angiography revealed a large flow void in the choriocapillaris, which has not been previously demonstrated. CONCLUSION: Multimodal imaging offers valuable information in the evaluation of patients with acute retinal necrosis.},
	keywords = {Adult, Female, Fluorescein Angiography, Fundus Oculi, Humans, Multimodal Imaging, Retinal Necrosis Syndrome, Acute, Tomography, Optical Coherence},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000978},
	author = {Wang, Jay C and Lu, Yifan and Sobrin, Lucia and Husain, Deeba}
}
@article {1549033,
	title = {Disorganisation of retinal inner layers is associated with reduced contrast sensitivity in retinal vein occlusion},
	journal = {Br J Ophthalmol},
	volume = {106},
	number = {2},
	year = {2022},
	month = {2022 Feb},
	pages = {241-245},
	abstract = {BACKGROUND/AIMS: To determine if disorganisation of retinal inner layers (DRIL) is associated with reduced contrast sensitivity (CS) in patients with retinal vein occlusion (RVO) with a history of macular oedema (ME). METHODS: Prospective, observational cohort study. Patients with a history of ME secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) from October 2017 to July 2019 at a single institution were included. Patients underwent complete ophthalmic examination, spectral domain optical coherence tomography (SD-OCT) and CS testing using the quick contrast sensitivity function (qCSF) method. Eyes with coexisting macular disease were excluded. SD-OCT images were analysed for presence and extent of DRIL, intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective foci, epiretinal membrane (ERM), external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption, central macular thickness (CMT) and central foveal thickness (CFT). Multivariable mixed-effect linear regressions were performed for the area under the log contrast sensitivity function (AULCSF) using Stata (StataCorp). P values \&lt;0.05 were considered significant. RESULTS: 58 visits from 31 patients were included (1.9{\textpm}1.2 visits per patient). 29 (50\%) were for CRVO. The average age was 63.9{\textpm}10.5\&nbsp;years. On multivariable analysis, DRIL extent (p\&lt;0.001), CMT (p=0.007), CFT (p=0.024) and moderate cataract (p=0.001) were significantly associated with worse AULCSF. CONCLUSIONS: DRIL extent is associated with reduced CS in eyes with ME secondary to RVO. DRIL is an imaging feature that has important implications for visual function.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2020-317615},
	author = {Wang, Jay and Cui, Ying and Vingopoulos, Filippos and Kasetty, Megan and Silverman, Rebecca F and Katz, Raviv and Kim, Leo and Miller, John B}
}
@article {630231,
	title = {The Eyes Absent Proteins in Developmental and Pathological Angiogenesis.},
	journal = {Am J Pathol},
	volume = {186},
	number = {3},
	year = {2016},
	month = {2016 Mar},
	pages = {568-78},
	abstract = {Management of neoangiogenesis remains a high-value therapeutic goal. A recently uncovered association between the DNA damage repair pathway and pathological angiogenesis could open previously unexplored possibilities for intervention. An attractive and novel target is the Eyes absent (EYA) tyrosine phosphatase, which plays a critical role in the repair versus apoptosis decision after DNA damage. This study examines the role of EYA in the postnatal development of the retinal vasculature and under conditions of ischemia-reperfusion encountered in proliferative retinopathies. We find that the ability of the EYA proteins to promote endothelial cell (EC) migration contributes to a delay in postnatal development of the retinal vasculature when Eya3 is deleted specifically in ECs. By using genetic and chemical biology tools, we show that EYA contributes to pathological angiogenesis in a model of oxygen-induced retinopathy. Both in\&nbsp;vivo and in\&nbsp;vitro, loss of EYA tyrosine phosphatase activity leads to defective assembly of γ-H2AX foci and thus to DNA damage repair in ECs under oxidative stress. These data reveal the potential utility of EYA tyrosine phosphatase inhibitors as therapeutic agents in inhibiting pathological neovascularization with a range of clinical applications.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2015.10.031},
	author = {Wang, Yuhua and Tadjuidje, Emmanuel and Pandey, Ram Naresh and Stefater, James A and Smith, Lois E H and Lang, Richard A and Hegde, Rashmi S}
}
@article {1483612,
	title = {Characterization of Central Visual Field Loss in End-stage Glaucoma by Unsupervised Artificial Intelligence},
	journal = {JAMA Ophthalmol},
	year = {2020},
	month = {2020 Jan 02},
	abstract = {Importance: Although the central visual field (VF) in end-stage glaucoma may substantially vary among patients, structure-function studies and quality-of-life assessments are impeded by the lack of appropriate characterization of end-stage VF loss. Objective: To provide a quantitative characterization and classification of central VF loss in end-stage glaucoma. Design, Setting, and Participants: This retrospective cohort study collected data from 5 US glaucoma services from June 1, 1999, through October 1, 2014. A total of 2912 reliable 10-2 VFs of 1103 eyes from 1010 patients measured after end-stage 24-2 VFs with a mean deviation (MD) of -22 dB or less were included in the analysis. Data were analyzed from March 28, 2018, through May 23, 2019. Main Outcomes and Measures: Central VF patterns were determined by an artificial intelligence algorithm termed archetypal analysis. Longitudinal analyses were performed to investigate whether the development of central VF defect mostly affects specific vulnerability zones. Results: Among the 1103 patients with the most recent VFs, mean (SD) age was 70.4 (14.3) years; mean (SD) 10-2 MD, -21.5 (5.6) dB. Fourteen central VF patterns were determined, including the most common temporal sparing patterns (304 [27.5\%]), followed by mostly nasal loss (280 [25.4\%]), hemifield loss (169 [15.3\%]), central island (120 [10.9\%]), total loss (91 [8.3\%]), nearly intact field (56 [5.1\%]), inferonasal quadrant sparing (42 [3.8\%]), and nearly total loss (41 [3.7\%]). Location-specific median total deviation analyses partitioned the central VF into a more vulnerable superonasal zone and a less vulnerable inferotemporal zone. At 1-year and 2-year follow-up, new defects mostly occurred in the more vulnerable zone. Initial encroachments on an intact central VF at follow-up were more likely to be from nasal loss (11 [18.4\%]; P \&lt; .001). One of the nasal loss patterns had a substantial chance at 2-year follow-up (8 [11.0\%]; P = .004) to shift to total loss, whereas others did not. Conclusions and Relevance: In this study, central VF loss in end-stage glaucoma was found to exhibit characteristic patterns that might be associated with different subtypes. Initial central VF loss is likely to be nasal loss, and 1 specific type of nasal loss is likely to develop into total loss.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.5413},
	author = {Wang, Mengyu and Tichelaar, Jorryt and Pasquale, Louis R and Shen, Lucy Q and Boland, Michael V and Wellik, Sarah R and De Moraes, Carlos Gustavo and Myers, Jonathan S and Ramulu, Pradeep and Kwon, MiYoung and Saeedi, Osamah J and Wang, Hui and Baniasadi, Neda and Li, Dian and Bex, Peter J and Tobias Elze}
}
@article {1363220,
	title = {Topical drug formulations for prolonged corneal anesthesia},
	journal = {Cornea},
	volume = {32},
	number = {7},
	year = {2013},
	month = {2013 Jul},
	pages = {1040-5},
	abstract = {PURPOSE: Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect of the site 1 sodium channel blocker tetrodotoxin (TTX) on the duration of corneal anesthesia, applied with either proparacaine (PPC) or the chemical permeation enhancer octyl-trimethyl ammonium bromide (OTAB). The effect of test solutions on corneal healing was also studied. METHODS: Solutions of TTX, PPC, and OTAB, singly or in combination, were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia was calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo after corneal debridement. RESULTS: Combination of TTX and PPC resulted in corneal anesthesia that was 8 to 10 times longer in duration than that from either drug administered alone, whereas OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed after coadministration of TTX and PPC. CONCLUSIONS: Coadministration of TTX and PPC significantly prolonged corneal anesthesia, but in view of delayed corneal reepithelialization, caution is suggested in the use of the drug combination.},
	keywords = {Anesthesia, Local, Anesthetics, Combined, Anesthetics, Local, Animals, Cell Line, Chemistry, Pharmaceutical, Cornea, Corneal Keratocytes, Epithelium, Corneal, Humans, Male, Propoxycaine, Quaternary Ammonium Compounds, Rats, Rats, Sprague-Dawley, Sodium Channel Blockers, Tetrodotoxin, Time Factors, Wound Healing},
	issn = {1536-4798},
	doi = {10.1097/ICO.0b013e31828cbfe6},
	author = {Wang, Liqiang and Shankarappa, Sahadev A and Tong, Rong and Ciolino, Joseph B and Tsui, Jonathan H and Chiang, Homer H and Kohane, Daniel S}
}
@article {1319488,
	title = {Outcomes of Boston keratoprosthesis type 1 reimplantation: multicentre study results},
	journal = {Can J Ophthalmol},
	volume = {53},
	number = {3},
	year = {2018},
	month = {2018 Jun},
	pages = {284-290},
	abstract = {OBJECTIVE: To investigate the visual and anatomical outcomes of Boston keratoprosthesis (Kpro) type 1 reimplantation. DESIGN: Subgroup analysis of multicentre prospective cohort study. PARTICIPANTS: Of 303 eyes that underwent Kpro implantation between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centres, 13 eyes of 13 patients who underwent reimplantation of Boston Kpro type 1 were compared with 13 eyes of 13 diagnosis-matched patients who underwent initial implantation. METHODS: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and analyzed. Main outcome measures were Kpro retention and logMAR visual acuity. RESULTS: After a mean follow-up time of 17.1 {\textpm} 17.6 months, the retention of both initial and repeat Kpro implantation was 92.3\% (12/13 in both groups), and 62\% of initial implantation and 58\% of repeat implantation eyes achieved visual acuity better than 20/200. Vision worse than 20/200 was often due to glaucoma or posterior segment pathology. Best-recorded logMAR visual acuity was significantly improved postoperatively in both groups (p \&lt; 0.001), and there was no statistically significant difference in final logMAR visual acuity between the 2 groups (p = 0.89). Sterile keratolysis (n = 4) and fungal infection (n = 5) were the most common causes of initial Kpro failure in the repeat Kpro group. The single failure in the repeat Kpro implantation group was due to fungal keratitis, and in the control group it was related to Kpro extrusion. CONCLUSIONS: Repeat Kpro implantation is a viable option after failed initial Kpro, with visual and anatomical outcomes comparable to those of initial procedures.},
	issn = {1715-3360},
	doi = {10.1016/j.jcjo.2017.10.021},
	author = {Wang, Jay C and Rudnisky, Christopher J and Belin, Michael W and Ciolino, Joseph B and Boston Type 1 Keratoprosthesis Study Group}
}
@article {1645450,
	title = {Decreased Macular Retinal Thickness in Patients With Pterygium},
	journal = {Front Neurol},
	volume = {13},
	year = {2022},
	month = {2022},
	pages = {881190},
	abstract = {Purpose: To explore alterations in macular retinal thickness (RT) and analyze correlation between macular RT and pterygium area, length in pterygium patients. Methods: Totally 13 patients with pterygium (left eye) and 13 healthy controls (left eye) were recruited. OCTA was applied to scan each eye to generate three-dimensional images. Based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method, each image was divided into nine subregions for the ETDRS: central (C); inner superior (IS); outer superior (OS); inner nasal (IN); outer nasal (ON); inner inferior (II); outer inferior (OI); inner temporal (IT); and outer temporal (OT). The macular RT in each subregion was measured. Furthermore, the correlation between RT and the area, length of pterygium was analyzed. Results: The visual acuity of pterygium patient was different from that of the control (P \&lt; 0.05). Besides, decreased intraretinal thickness of the IN and ON, increased intraretinal thickness of OT, decreased extraretinal thickness of OT, IN, ON, OS, and decreased retinal full layer thickness of medial superior, OS, IN, ON, and II subregions in pterygium group were observed. There was a negative correlation between RT of the IN and ON subregions and the length of pterygium (r = -0.5803 and r = -0.6013, P = 0.0376 and P = 0.0297). The RT of IN subregion was negatively correlated with pterygium area (r = -0.5844, P = 0.0359). According to the receiver operating characteristic analysis, in the ON subregion, the areas under the curve of the inner retinal thickness, outer retinal thickness and the whole retinal thickness were 1.0 (95\% CI: 1.0), 0.882 (95\% CI: 0.715 and 0.963), and 1.0 (95\% CI: 1.0). The smallest area under the curve of retinal thickness in OT subregion was 0.018 (95\% CI: 0-0.059). Conclusion: RT of pterygium patients was significantly decreased, and the main alterations occurred in the temporal side suggesting there might exist retinal structural alterations in pterygium.},
	issn = {1664-2295},
	doi = {10.3389/fneur.2022.881190},
	author = {Wang, Feng and Liu, Li Qi and Liang, Rong Bin and Zhang, Li Juan and Shu, Hui Ye and Liao, Xu Lin and Pan, Yi Cong and Wu, Jieli and Su, Ting and Shao, Yi}
}
@article {1016141,
	title = {Astrocytes in the Optic Nerve Head of Glaucomatous Mice Display a Characteristic Reactive Phenotype},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {2},
	year = {2017},
	month = {2017 Feb 01},
	pages = {924-932},
	abstract = {Purpose: Optic nerve head astrocytes, a subtype of white-matter astrocytes, become reactive early in the course of glaucoma. It was shown recently that in the DBA/2J mouse model of inherited glaucoma optic nerve astrocytes extend new longitudinal processes into the axon bundles before ganglion cell loss becomes apparent. The present study aims at testing whether this behavior of astrocytes is typical of early glaucomatous damage. Methods: Mice expressing green fluorescent protein in individual astrocytes were used to evaluate the early response of astrocytes in the glial lamina of the optic nerve head after increasing the IOP using the microbead occlusion method. Tissue sections from the glial lamina were imaged consecutively by confocal and electron microscopy. Results: Confocal and electron microscope images show that astrocytes close to the myelination transition zone in the hypertensive nerve heads extend new processes that follow the longitudinal axis of the optic nerve and invade axon bundles in the nerve head. Ultrastructurally, the longitudinal processes were largely devoid of subcellular organelles except for degenerating mitochondria. Conclusions: The longitudinal processes are a common feature of glaucomatous optic nerve astrocytes, whereas they are not observed after traumatic nerve injury. Thus, astrocytes appear to fine-tune their responses to the nature and/or timing of the injury to the neurons that they surround.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20571},
	author = {Wang, Rui and Seifert, Philip and Jakobs, Tatjana C}
}
@article {1417580,
	title = {Comparison of choroidal neovascularization secondary to white dot syndromes and age-related macular degeneration by using optical coherence tomography angiography},
	journal = {Clin Ophthalmol},
	volume = {13},
	year = {2019},
	month = {2019},
	pages = {95-105},
	abstract = {Purpose: To characterize and compare choroidal neovascularization (CNV) secondary to white dot syndromes (WDS) and age-related macular degeneration (AMD) using optical coherence tomography angiography (OCT-A). Methods: This is a cross-sectional study in which we imaged patients with CNV secondary to WDS and AMD with either the Zeiss Angioplex OCT-A or Optovue AngioVue OCT-A. Relevant demographic and clinical characteristics were collected and analyzed. CNV area and vessel density (VD) were measured by three independent graders, and linear regression analysis was subsequently performed. Results: Three patients with multifocal choroiditis and panuveitis, one patient each with birdshot chorioretinopathy, presumed ocular histoplasmosis syndrome, and persistent placoid maculopathy, and eleven patients with AMD with sufficient image quality were included. CNV associated with WDS was significantly smaller than that secondary to AMD (0.56{\textpm}0.32 vs 2.79{\textpm}1.80 mm, =-2.22, =0.01), while no difference in VD was detected (0.46{\textpm}0.09 vs 0.44{\textpm}0.09, =0.02, =0.71). Conclusion: CNV networks secondary to WDS appear to be smaller than those secondary to AMD but have similar VD. OCT-A is a powerful tool to investigate properties of CNV from various etiologies. Larger studies are needed for further characterization and understanding of CNV pathogenesis in inflammatory conditions.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S185468},
	author = {Wang, Jay C and McKay, Kenneth M and Sood, Arjun B and La{\'\i}ns, In{\^e}s and Sobrin, Lucia and Miller, John B}
}
@article {1424820,
	title = {Intravenous treatment of choroidal neovascularization by photo-targeted nanoparticles},
	journal = {Nat Commun},
	volume = {10},
	number = {1},
	year = {2019},
	month = {2019 Feb 18},
	pages = {804},
	abstract = {Choroidal neovascularization (CNV) is the major cause of vision loss in wet age-related macular degeneration (AMD). Current therapies require repeated intravitreal injections, which are painful and can cause infection, bleeding, and retinal detachment. Here we develop nanoparticles (NP-[CPP]) that can be administered intravenously and allow local drug delivery to the diseased choroid via light-triggered targeting. NP-[CPP] is formed by PEG-PLA chains modified with a cell penetrating peptide (CPP). Attachment of a DEACM photocleavable group to the CPP inhibits cellular uptake of NP-[CPP]. Irradiation with blue light cleaves DEACM\&nbsp;from the CPP, allowing the CPP to migrate from the NP core to the surface, rendering it active. In mice with laser-induced CNV, intravenous injection of NP-[CPP] coupled to irradiation of the eye allows NP accumulation in the neovascular lesions. When loaded with doxorubicin, irradiated NP-[CPP] significantly reduces neovascular lesion size. We propose a strategy for non-invasive treatment of CNV and enhanced drug accumulation specifically in diseased areas of the eye.},
	issn = {2041-1723},
	doi = {10.1038/s41467-019-08690-4},
	author = {Wang, Yanfei and Liu, Chi-Hsiu and Ji, Tianjiao and Mehta, Manisha and Wang, Weiping and Marino, Elizabeth and Chen, Jing and Kohane, Daniel S}
}
@article {688676,
	title = {Oral Contraceptive Use and Prevalence of Self-Reported Glaucoma or Ocular Hypertension in the United States.},
	journal = {Ophthalmology},
	volume = {123},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {729-36},
	abstract = {PURPOSE: To investigate the association between oral contraceptive (OC) use and glaucoma prevalence in the United States. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 3406 female participants, aged 40 years or older, from the 2005 to 2008 National Health and Nutrition Examination Survey, who reported a presence or absence of glaucoma or ocular hypertension completed both the vision and the reproductive health questionnaires and underwent eye examinations. METHODS: Multivariate regression analysis was used to assess the correlation between OC use and self-reported glaucoma or ocular hypertension (n\&nbsp;= 231 cases), controlling for potential confounders, including age, ethnicity, systemic comorbidities such as hypertension and stroke, ocular diseases such as cataract and diabetic retinopathy, and reproductive health factors, including age at menopause, age at menarche, history of hormone replacement therapy, and gynecological surgical history. MAIN OUTCOME MEASURES: The outcome variable was self-reported glaucoma or ocular hypertension. RESULTS: After adjusting for confounders, those with >=3 years of OC use had greater odds (odds ratio, 1.94; 95\% confidence interval, 1.22-3.07) of self-reported glaucoma or ocular hypertension. Other factors associated with higher glaucoma or ocular hypertension prevalence included older age, African American race, and later age at menarche. CONCLUSIONS: Oral contraceptive use may be associated with increased risk of self-reported glaucoma or ocular hypertension.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.11.029},
	author = {Wang, Ye Elaine and Kakigi, Caitlin and Barbosa, Diego and Porco, Travis and Chen, Rebecca and Wang, Sophia and Li, Yingjie and Singh, Kuldev and Pasquale, Louis R and Lin, Shan C}
}
@article {1642385,
	title = {Change blindness in simulated driving in individuals with homonymous visual field loss},
	journal = {Cogn Res Princ Implic},
	volume = {7},
	number = {1},
	year = {2022},
	pages = {44},
	author = {S. Wang and Xu J and Baliutaviciute V and Bowers A}
}
@article {1661592,
	title = {Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis},
	journal = {Elife},
	volume = {11},
	year = {2022},
	month = {2022 Dec 01},
	abstract = {Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that Slc38a5 is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. Slc38a5 is suppressed in retinal blood vessels from Lrp5-/- and Ndpy/- mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, Slc38a5 transcription is regulated by Wnt/β-catenin signaling. Genetic deficiency of Slc38a5 in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of SLC38A5 in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.},
	keywords = {Amino Acid Transport Systems, Amino Acid Transport Systems, Neutral, Animals, Endothelial Cells, Glutamine, Humans, Mice, Neovascularization, Pathologic, Vascular Endothelial Growth Factor A},
	issn = {2050-084X},
	doi = {10.7554/eLife.73105},
	author = {Wang, Zhongxiao and Yemanyi, Felix and Blomfield, Alexandra K and Bora, Kiran and Huang, Shuo and Liu, Chi-Hsiu and Britton, William R and Cho, Steve S and Tomita, Yohei and Fu, Zhongjie and Ma, Jian-Xing and Li, Wen-Hong and Chen, Jing}
}
@article {1698241,
	title = {ROS-sensitive Crocin-loaded chitosan microspheres for lung targeting and attenuation of radiation-induced lung injury},
	journal = {Carbohydr Polym},
	volume = {307},
	year = {2023},
	month = {2023 May 01},
	pages = {120628},
	abstract = {Radiation-induced lung injury (RILI) is one of the major complications in patients exposed to accidental radiation and radiotherapy for thoracic malignancies. However, there is no reliable radioprotector for effective clinical treatment of RILI so far. Herein, a novel Crocin-loaded chitosan microsphere is developed for lung targeting and attenuation of RILI. The chitosan microspheres are modified with 4-carboxyphenylboronic acid and loaded with the natural antioxidant Crocin-I to give the drug-loaded microspheres (~10\&nbsp;μm). The microspheres possess good biocompatibility in vivo and in vitro. In a mouse model, they exhibit effective passive targeting performance and a long retention time in the lung after intravenous administration. Furthermore, they improve the radioprotective effect of Crocin-I for the treatment of RILI by reducing the level of inflammatory cytokines in bronchoalveolar lavage fluid and by regulating oxidative stress in lung tissues. The targeted agents significantly improved the bioavailability and radioprotection of Crocin-I by the outstanding passive targeting effect. This work may provide a promising strategy for efficient radioprotection on RILI using passive lung targeting microspheres.},
	keywords = {Animals, Chitosan, Lung, Lung Injury, Mice, Microspheres, Reactive Oxygen Species},
	issn = {1879-1344},
	doi = {10.1016/j.carbpol.2023.120628},
	author = {Wang, Lu and Liu, Chang and Lu, Weihong and Xu, Longjiang and Kuang, Liangju and Hua, Daoben}
}
@article {1125406,
	title = {Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain},
	journal = {Diabetes},
	volume = {66},
	number = {10},
	year = {2017},
	month = {2017 Oct},
	pages = {2704-2712},
	abstract = {Whether change in physical activity over time modifies the genetic susceptibility to long-term weight gain is unknown. We calculated a BMI-genetic risk score (GRS) based on 77 BMI-associated single nucleotide polymorphisms (SNPs) and a body fat percentage (BF\%)-GRS based on 12 BF\%-associated SNPs in 9,390 women from the Nurses{\textquoteright} Health Study (NHS) and 5,291 men from the Health Professionals Follow-Up Study (HPFS). We analyzed the interactions between each GRS and change in physical activity on BMI/body weight change within five 4-year intervals from 1986 to 2006 using multivariable generalized linear models with repeated-measures analyses. Both the BMI-GRS and the BF\%-GRS were associated with long-term increases in BMI/weight, and change in physical activity consistently interacted with the BF\%-GRS on BMI change in the NHS (P for interaction = 0.025) and HPFS (P for interaction = 0.001). In the combined cohorts, 4-year BMI change per 10-risk allele increment was -0.02 kg/m(2) among participants with greatest increase in physical activity and 0.24 kg/m(2) among those with greatest decrease in physical activity (P for interaction \&lt; 0.001), corresponding to 0.01 kg versus 0.63 kg weight changes every 4 years (P for interaction = 0.001). Similar but marginal interactions were observed for the BMI-GRS (P for interaction = 0.045). Our data indicate that the genetic susceptibility to weight gain may be diminished by increasing physical activity.},
	keywords = {Adult, Aged, Body Mass Index, Body Weight, Exercise, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Prospective Studies, Weight Gain},
	issn = {1939-327X},
	doi = {10.2337/db17-0071},
	author = {Wang, Tiange and Huang, Tao and Heianza, Yoriko and Sun, Dianjianyi and Zheng, Yan and Ma, Wenjie and Jensen, Majken K and Kang, Jae H and Wiggs, Janey L and Pasquale, Louis R and Rimm, Eric B and Manson, JoAnn E and Hu, Frank B and Willett, Walter C and Qi, Lu}
}
@article {1452962,
	title = {Identification of two novel RHO mutations in Chinese retinitis pigmentosa patients},
	journal = {Exp Eye Res},
	volume = {188},
	year = {2019},
	month = {2019 Nov},
	pages = {107726},
	abstract = {Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinal diseases with more than 80 identified causative genes to date. Mutations in the RHO (rhodopsin, OMIM, 180380) are the most common cause of autosomal dominant RP (adRP) worldwide. RHO is also one of the few RP genes that can cause autosomal recessive RP (arRP). To explore the frequency of RP mutations in Chinese populations, panel-based NGS (next-generation sequencing) screening and Sanger sequencing validation were performed for RP patients from 72 unrelated Chinese families. Here we reported the identified mutations only in the RHO gene. Our results showed that 4 mutations in RHO were detected in 5 (6.94\%) of the 72 RP families, including two known missense mutations, c.158C \&gt; G (p.P53R) and c.551A \&gt; C (p.Q184P), and two novel mutations, c.34delC (p.P12NA) and c.82C \&gt; T (p.Q28X). The c.34delC (p.P12NA) mutation was detected in heterozygous state in one patient with intermediate RP phenotype. The c.82C \&gt; T (p.Q28X) mutation was found in a homozygous state in one proband with advanced RP phenotype at the age of 32. Clinical examination of the heterozygous carriers of c.82C \&gt; T (p.Q28X) in that family showed that the father at the age of 60s experienced no symptoms of RP and normal fundus examinations but displayed reduced electroretinography (ERG) and abnormal visual field. The sister and brother at the age of 30s showed no typical aspects of RP phenotypes. Our results not only expand the mutation spectrum of the RHO gene, but also suggest that the 2 null mutations might play minor dominant effects, leading to less severe and slower retinal degeneration in heterozygous state and more severe phenotype in homozygous state.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.107726},
	author = {Wang, Juan and Xu, Ding and Zhu, Tong and Zhou, Yue and Xin Chen and Wang, Fang and Zhang, Jieping and Tian, Haibin and Gao, Furong and Zhang, Jingfa and Jin, Caixia and Xu, Jingying and Lu, Lixia and Liu, Qin and Xu, Guo-Tong}
}
@article {382456,
	title = {Nanoparticle-mediated expression of a wnt pathway inhibitor ameliorates ocular neovascularization.},
	journal = {Arterioscler Thromb Vasc Biol},
	volume = {35},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {855-64},
	abstract = {OBJECTIVE: The deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues. APPROACH AND RESULTS: A plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP). Nanoparticles containing a plasmid expressing the low-density lipoprotein receptor extracellular domain nanoparticle were used as negative control. MTT, modified Boyden chamber, and Matrigel ({\texttrademark}) assays were used to evaluate the inhibitory effect of VLN-NP on Wnt3a-stimulated endothelial cell proliferation, migration, and tube formation. Vldlr(-/-) mice, oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models were used to evaluate the effect of VLN-NP on ocular neovascularization. Wnt reporter mice (BAT-gal), Western blotting, and luciferase assay were used to evaluate Wnt pathway activity. Our results showed that VLN-NP specifically inhibited Wnt3a-induced endothelial cell proliferation, migration, and tube formation. Intravitreal injection of VLN-NP inhibited abnormal neovascularization in Vldlr(-/-), oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models, compared with low-density lipoprotein receptor extracellular domain nanoparticle. VLN-NP significantly inhibited the phosphorylation of low-density lipoprotein receptor-related protein 6, the accumulation of β-catenin, and the expression of vascular endothelial growth factor in vivo and in vitro. CONCLUSIONS: Taken together, these results suggest that the soluble VLN is a negative regulator of the Wnt pathway and has antiangiogenic activities. Nanoparticle-mediated expression of VLN may thus represent a novel therapeutic approach to treat pathological ocular angiogenesis and potentially other vascular diseases affected by Wnt signaling.},
	issn = {1524-4636},
	doi = {10.1161/ATVBAHA.114.304627},
	author = {Wang, Zhongxiao and Cheng, Rui and Lee, Kyungwon and Tyagi, Puneet and Ding, Lexi and Kompella, Uday B and Chen, Jing and Xu, Xun and Ma, Jian-Xing}
}
@article {1435422,
	title = {Soluble CX3CL1 gene therapy improves cone survival and function in mouse models of retinitis pigmentosa},
	journal = {Proc Natl Acad Sci U S A},
	volume = {116},
	number = {20},
	year = {2019},
	month = {2019 May 14},
	pages = {10140-10149},
	abstract = {Retinitis pigmentosa (RP) is a disease that initially presents as night blindness due to genetic deficits in the rod photoreceptors of the retina. Rods then die, causing dysfunction and death of cone photoreceptors, the cell type that mediates high acuity and color vision, ultimately leading to blindness. We investigated immune responses in mouse models of RP and found evidence of microglia activation throughout the period of cone degeneration. Using adeno-associated vectors (AAVs), delivery of genes encoding microglial regulatory signals led to the identification of AAV serotype 8 (AAV8) soluble CX3CL1 (sCX3CL1) as a promising therapy for degenerating cones. Subretinal injection of AAV8-sCX3CL1 significantly prolonged cone survival in three strains of RP mice. Rescue of cones was accompanied by improvements in visual function. AAV8-sCX3CL1 did not affect rod survival, microglia localization, or inflammatory cytokine levels in the retina. Furthermore, although RNA sequencing of microglia demonstrated marked transcriptional changes with AAV8-sCX3CL1, pharmacological depletion of up to \~{}99\% of microglia failed to abrogate the effect of AAV8-sCX3CL1 on cone survival. These findings indicate that AAV8-sCX3CL1 can rescue cones in multiple mouse models of RP via a pathway that does not require normal numbers of microglia. Gene therapy with sCX3CL1 is a promising mutation-independent approach to preserve vision in RP and potentially other forms of retinal degeneration.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1901787116},
	author = {Wang, Sean K and Xue, Yunlu and Rana, Parimal and Hong, Christin M and Cepko, Constance L}
}
@article {1439867,
	title = {For Mass Eye and Ear Special Issue: Optical Coherence Tomography Angiography: Review of Current Technical Aspects and Applications in Chorioretinal Disease},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 May 26},
	pages = {1-7},
	abstract = {Optical coherence tomography angiography (OCT-A) has enabled fast, non-invasive, high-resolution visualization of vasculature within the eye. In the past few years, it has become increasingly utilized for a range of disorders including age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and uveitis among others. This article reviews technical aspects of OCT-A, its applications in chorioretinal disease, and known limitations of the technology.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620797},
	author = {Wang, Jay C and Miller, John B}
}
@article {1307455,
	title = {Myeloid sarcoma involving the greater wing of the sphenoid bone and additional skeletal sites presenting with unilateral proptosis and fevers},
	journal = {Orbit},
	year = {2018},
	month = {2018 Mar 20},
	pages = {1-4},
	abstract = {We report a case of myeloid sarcoma with multifocal skeletal involvement, including the greater wing of the sphenoid bone. A 23-month-old boy presented with left-sided proptosis and fevers, and was found to have an infiltrative mass involving the left sphenoid bone on orbital imaging. Full body imaging further demonstrated multiple bony lesions in the pelvis, thoracic and lumbar vertebrae, bilateral femura, and left humerus, and biopsies of the humerus were consistent with myeloid sarcoma. The patient was started on a standard chemotherapy regimen and is responding well. Myeloid sarcoma presenting with proptosis due to sphenoid bone involvement with simultaneous multifocal skeletal involvement is very uncommon and highlights the importance of biopsy for establishing a definitive diagnosis.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2018.1449225},
	author = {Wang, Jay C and Jim{\'e}nez P{\'e}rez, Juan C and Friedmann, Alison M and Louissaint, Abner and Freitag, Suzanne K}
}
@article {1511490,
	title = {Long-term Outcomes of Punctal Cauterization in the Management of Ocular Surface Diseases},
	journal = {Cornea},
	volume = {40},
	number = {2},
	year = {2021},
	month = {2021 Feb 01},
	pages = {168-171},
	abstract = {PURPOSE: To evaluate the long-term outcomes of surgical occlusion of lacrimal puncta using thermal cautery in the management of ocular surface diseases. METHODS: We reviewed medical records of 80 consecutive patients from a single academic center who underwent punctal cauterization. Patient demographics, ocular history, symptoms, and signs of ocular surface diseases pre- and post-cauterization were recorded. RESULTS: A total of 80 patients (171 puncta) were included, with an average age of 59 years and a follow-up duration of 27 months. The most common ocular morbidity was ocular graft-versus-host disease (n = 36), followed by primary keratoconjunctivitis sicca (n = 15). Indications for punctal cauterization included plug loss (n = 51), difficulty in plug fitting (n = 11), plug-related complications (n = 6), recanalization of previous cauterization (n = 7), and severe ocular surface disease requiring permanent punctal closure (n = 4). After punctal cauterization, the percentage of eyes with severe (21\%) and moderate (25\%) dry eye decreased significantly (8\% and 19\% at 3 months and 6\% and 17\% at 12 months, P = 0.0006). Fifty-four percent of patients reported improvement in their symptoms. The rate of recanalization was 21\% during the follow-up period. The use of topical corticosteroids was associated with higher recanalization rate. Associated complications were limited to temporary pain and swelling. CONCLUSIONS: Punctal cauterization is an effective modality in treating severe ocular surface diseases in patients who repeatedly lose punctal plugs, and it can be easily performed in a clinic setting without major complications. However, cauterization may need to be repeated in up to a quarter of cases because of recanalization.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000002384},
	author = {Wang, Yvonne and Carreno-Galeano, Jimena Tatiana and Singh, Rohan Bir and Dana, Reza and Yin, Jia}
}
@article {1179206,
	title = {Acute Zonal Occult Outer Retinopathy Associated With Retrobulbar Optic Neuritis},
	journal = {J Neuroophthalmol},
	volume = {37},
	number = {3},
	year = {2017},
	month = {2017 Sep},
	pages = {287-290},
	abstract = {A 17-year-old girl presented with unilateral retrobulbar optic neuritis as well as bilateral funduscopic findings and outer retinal dysfunction suggestive of acute zonal occult outer retinopathy (AZOOR). Fundus autofluorescence abnormalities, visual field loss, and electroretinographic changes were supportive of bilateral AZOOR. MRI was consistent with the diagnosis of clinically isolated syndrome (CIS), which is defined as a central nervous system demyelinating event that may herald the onset of multiple sclerosis (MS). While AZOOR previously has been linked to MS and demyelinating white matter lesions in the brain, our case seems unique due to concurrent development of AZOOR and retrobulbar optic neuritis as a CIS.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000494},
	author = {Wang, Jay C and Finn, Avni P and Grotting, Lindsay A and Sobrin, Lucia}
}
@article {1213861,
	title = {Diabetic Choroidopathy: Choroidal Vascular Density and Volume in Diabetic Retinopathy With Swept-Source Optical Coherence Tomography},
	journal = {Am J Ophthalmol},
	volume = {184},
	year = {2017},
	month = {2017 Dec},
	pages = {75-83},
	abstract = {PURPOSE: To compare choroidal vascular density (CVD) and volume (CVV) in diabetic eyes and controls, using en face swept-source optical coherence tomography (SS-OCT). DESIGN: Prospective cross-sectional study. METHODS: Setting: Multicenter. PATIENT POPULATION: Total of 143 diabetic eyes-27 with no diabetic retinopathy (DR), 47 with nonproliferative DR (NPDR), 51 with NPDR and diabetic macular edema (DME), and 18 with proliferative DR (PDR)-and 64 age-matched nondiabetic control eyes. OBSERVATION PROCEDURES: Complete ophthalmologic examination and SS-OCT imaging. En face SS-OCT images of the choroidal vasculature were binarized. MAIN OUTCOME MEASURES: CVD, calculated as the percent area occupied by choroidal vessels in the central macular region (6-mm-diameter circle centered on the fovea), and throughout the posterior pole (12\&nbsp;{\texttimes} 9\&nbsp;mm). The central macular CVV was calculated by multiplying the average CVD by macular area and choroidal thickness (obtained with SS-OCT automated software). Multilevel mixed linear models were performed for analyses. RESULTS: Compared to controls (0.31 {\textpm} 0.07), central macular CVD was significantly decreased by 9\% in eyes with NPDR\&nbsp;+ DME (0.28 {\textpm} 0.06; {\ss}\&nbsp;=\&nbsp;-0.03, P\&nbsp;=\&nbsp;.02) and by 15\% in PDR (0.26 {\textpm} 0.05; {\ss}\&nbsp;=\&nbsp;-0.04, P\&nbsp;= .01). The central macular CVV was significantly decreased by 19\% in eyes with PDR (0.020 {\textpm} 0.005\&nbsp;mm3, {\ss}\&nbsp;=\&nbsp;-0.01, P\&nbsp;= .01) compared to controls (0.025 {\textpm} 0.01\&nbsp;mm3). CONCLUSIONS: Choroidal vascular density and volume are significantly reduced in more advanced stages of diabetic retinopathy. New imaging modalities should allow further exploration of the contributions of choroidal vessel disease to diabetic eye disease pathogenesis, prognosis, and treatment response.},
	keywords = {Aged, Choroid, Cross-Sectional Studies, Diabetic Retinopathy, Female, Fluorescein Angiography, Fundus Oculi, Humans, Imaging, Three-Dimensional, Male, Middle Aged, Prospective Studies, Retinal Vessels, Tomography, Optical Coherence, Visual Acuity},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2017.09.030},
	author = {Wang, Jay C and La{\'\i}ns, In{\^e}s and Provid{\^e}ncia, Joana and Armstrong, Grayson W and Santos, Ana R and Gil, Pedro and Gil, Jo{\~a}o and Talcott, Katherine E and Marques, Jo{\~a}o H and Figueira, Jo{\~a}o and Vavvas, Demetrios G and Kim, Ivana K and Miller, Joan W and Husain, Deeba and Silva, Rufino and Miller, John B}
}
@article {1619410,
	title = {Myeloid lineage contributes to pathological choroidal neovascularization formation via SOCS3},
	journal = {EBioMedicine},
	volume = {73},
	year = {2021},
	month = {2021 Nov},
	pages = {103632},
	abstract = {BACKGROUND: Pathological neovascularization in neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. Increasing evidence shows that cells of myeloid lineage play important roles in controlling pathological endothelium formation. Suppressor of cytokine signaling 3 (SOCS3) pathway has been linked to neovascularization. METHODS: We utilised a laser-induced choroidal neovascularization (CNV) mouse model to investigate the neovascular aspect of human AMD. In several cell lineage reporter mice, bone marrow chimeric mice and Socs3 loss-of-function (knockout) and gain-of-function (overexpression) mice, immunohistochemistry, confocal, and choroidal explant co-culture with bone marrow-derived macrophage medium were used to study the mechanisms underlying pathological CNV formation via myeloid SOCS3. FINDINGS: SOCS3 was significantly induced in myeloid lineage cells, which were recruited into the CNV lesion area. Myeloid Socs3 overexpression inhibited laser-induced CNV, reduced myeloid lineage-derived macrophage/microglia recruitment onsite, and attenuated pro-inflammatory factor expression. Moreover, SOCS3 in myeloid regulated vascular sprouting ex vivo in choroid explants and SOCS3 agonist reduced in vivo CNV. INTERPRETATION: These findings suggest that myeloid lineage cells contributed to pathological CNV formation regulated by SOCS3. FUNDING: This project was funded by NIH/NEI (R01EY030140, R01EY029238), BrightFocus Foundation, American Health Assistance Foundation (AHAF), and Boston Children{\textquoteright}s Hospital Ophthalmology Foundation for YS and the National Institutes of Health/National Heart, Lung and Blood Institute (U01HL098166) for PZ.},
	issn = {2352-3964},
	doi = {10.1016/j.ebiom.2021.103632},
	author = {Wang, Tianxi and Pingzhu Zhou and Xie, Xuemei and Tomita, Yohei and Cho, Steve and Tsirukis, Demetrios and Lam, Enton and Luo, Hongbo Robert and Sun, Ye}
}
@article {1642028,
	title = {The genetic basis for adult onset glaucoma: Recent advances and future directions},
	journal = {Prog Retin Eye Res},
	volume = {90},
	year = {2022},
	month = {2022 Sep},
	pages = {101066},
	abstract = {Glaucoma, a diverse group of eye disorders that results in the degeneration of retinal ganglion cells, is the world{\textquoteright}s leading cause of irreversible blindness. Apart from age and ancestry, the major risk factor for glaucoma is increased intraocular pressure (IOP). In primary open-angle glaucoma (POAG), the anterior chamber angle is open but there is resistance to aqueous outflow. In primary angle-closure glaucoma (PACG), crowding of the anterior chamber angle due to anatomical alterations impede aqueous drainage through the angle. In exfoliation syndrome and exfoliation glaucoma, deposition of white flaky material throughout the anterior chamber directly interfere with aqueous outflow. Observational studies have established that there is a strong hereditable component for glaucoma onset and progression. Indeed, a succession of genome wide association studies (GWAS) that were centered upon single nucleotide polymorphisms (SNP) have yielded more than a hundred genetic markers associated with glaucoma risk. However, a shortcoming of GWAS studies is the difficulty in identifying the actual effector genes responsible for disease pathogenesis. Building on the foundation laid by GWAS studies, research groups have recently begun to perform whole exome-sequencing to evaluate the contribution of protein-changing, coding sequence genetic variants to glaucoma risk. The adoption of this technology in both large population-based studies as well as family studies are revealing the presence of novel, protein-changing genetic variants that could enrich our understanding of the pathogenesis of glaucoma. This review will cover recent advances in the genetics of primary open-angle glaucoma, primary angle-closure glaucoma and exfoliation glaucoma, which collectively make up the vast majority of all glaucoma cases in the world today. We will discuss how recent advances in research methodology have uncovered new risk genes, and how follow up biological investigations could be undertaken in order to define how the risk encoded by a genetic sequence variant comes into play in patients. We will also hypothesise how data arising from characterising these genetic variants could be utilized to predict glaucoma risk and the manner in which new therapeutic strategies might be informed.},
	keywords = {Exfoliation Syndrome, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Glaucoma, Angle-Closure, Glaucoma, Open-Angle, Humans, Intraocular Pressure},
	issn = {1873-1635},
	doi = {10.1016/j.preteyeres.2022.101066},
	author = {Wang, Zhenxun and Wiggs, Janey L and Aung, Tin and Khawaja, Anthony P and Khor, Chiea Chuen}
}
@article {931171,
	title = {Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.},
	journal = {Am J Pathol},
	volume = {186},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {2588-600},
	abstract = {Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2016.06.015},
	author = {Wang, Zhongxiao and Liu, Chi-Hsiu and Sun, Ye and Gong, Yan and Favazza, Tara L and Morss, Peyton C and Saba, Nicholas J and Fredrick, Thomas W and He, Xi and Akula, James D and Chen, Jing}
}
@article {1417581,
	title = {An Artificial Intelligence Approach to Detect Visual Field Progression in Glaucoma Based on Spatial Pattern Analysis},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {1},
	year = {2019},
	month = {2019 Jan 02},
	pages = {365-375},
	abstract = {Purpose: To detect visual field (VF) progression by analyzing spatial pattern changes. Methods: We selected 12,217 eyes from 7360 patients with at least five reliable 24-2 VFs and 5 years of follow-up with an interval of at least 6 months. VFs were decomposed into 16 archetype patterns previously derived by artificial intelligence techniques. Linear regressions were applied to the 16 archetype weights of VF series over time. We defined progression as the decrease rate of the normal archetype or any increase rate of the 15 VF defect archetypes to be outside normal limits. The archetype method was compared with mean deviation (MD) slope, Advanced Glaucoma Intervention Study (AGIS) scoring, Collaborative Initial Glaucoma Treatment Study (CIGTS) scoring, and the permutation of pointwise linear regression (PoPLR), and was validated by a subset of VFs assessed by three glaucoma specialists. Results: In the method development cohort of 11,817 eyes, the archetype method agreed more with MD slope (kappa: 0.37) and PoPLR (0.33) than AGIS (0.12) and CIGTS (0.22). The most frequently progressed patterns included decreased normal pattern (63.7\%), and increased nasal steps (16.4\%), altitudinal loss (15.9\%), superior-peripheral defect (12.1\%), paracentral/central defects (10.5\%), and near total loss (10.4\%). In the clinical validation cohort of 397 eyes with 27.5\% of confirmed progression, the agreement (kappa) and accuracy (mean of hit rate and correct rejection rate) of the archetype method (0.51 and 0.77) significantly (P \&lt; 0.001 for all) outperformed AGIS (0.06 and 0.52), CIGTS (0.24 and 0.59), MD slope (0.21 and 0.59), and PoPLR (0.26 and 0.60). Conclusions: The archetype method can inform clinicians of VF progression patterns.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-25568},
	author = {Wang, Mengyu and Shen, Lucy Q and Pasquale, Louis R and Petrakos, Paul and Formica, Sydney and Boland, Michael V and Wellik, Sarah R and De Moraes, Carlos Gustavo and Myers, Jonathan S and Saeedi, Osamah and Wang, Hui and Baniasadi, Neda and Li, Dian and Tichelaar, Jorryt and Bex, Peter J and Tobias Elze}
}
@article {959486,
	title = {SPONTANEOUS CLOSURE OF A MACULAR HOLE AFTER FOUR FAILED VITRECTOMIES IN THE SETTING OF NF-1.},
	journal = {Retin Cases Brief Rep},
	year = {2016},
	month = {2016 Nov 09},
	abstract = {PURPOSE: To present the case of a patient who developed spontaneous closure of an idiopathic macular hole after four failed attempts at surgical closure. METHODS: This is a retrospective case review of the medical record of a single patient. No statistical analysis was performed. The patient is a 71-year-old white woman with neurofibromatosis Type 1 who presented to the retina clinic of one of the authors. RESULTS: The patient underwent four vitrectomies with long acting gas by two surgeons over the course of 2 years. After each surgery, the hole either did not close or it closed and then reopened within 1 year. Five months after the last surgery (1 year after the hole last reopened), the patient presented with improved vision and spontaneous closure of the macular hole. The hole has remained closed since then. CONCLUSION: This case demonstrates that spontaneous closure of a macular hole, associated with excellent visual recovery, can occur after multiple surgical failures. We propose that enhanced scar formation due to neurofibromatosis Type 1 was responsible for both the numerous failures following initially successful surgery (centrifugal traction) and for the spontaneous closure (centripetal traction).},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000408},
	author = {Wannamaker, Kendall W and Sharpe, Robert A and Kylstra, Jan A}
}
@article {1635635,
	title = {Solving neurodegeneration: common mechanisms and strategies for new treatments},
	journal = {Mol Neurodegener},
	volume = {17},
	number = {1},
	year = {2022},
	month = {2022 Mar 21},
	pages = {23},
	abstract = {Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address these mechanisms and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus Foundation, and the Melza M. and Frank Theodore Barr Foundation collaborated to bring together key opinion leaders and experts in the field of neurodegenerative disease for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the world{\textquoteright}s leading cause of irreversible blindness and the common interest of the three hosting foundations. Glaucoma, which causes vision loss through degeneration of the optic nerve, likely shares early cellular and molecular events with other neurodegenerative diseases of the central nervous system. Here we discuss major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions. We summarize important discussion points with emphasis on the research areas that are most innovative and promising in the treatment of neurodegeneration yet require further development. The research that is highlighted provides unique opportunities for collaboration that will lead to efforts in preventing neurodegeneration and ultimately vision loss.},
	issn = {1750-1326},
	doi = {10.1186/s13024-022-00524-0},
	author = {Wareham, Lauren K and Liddelow, Shane A and Temple, Sally and Benowitz, Larry I and Di Polo, Adriana and Wellington, Cheryl and Goldberg, Jeffrey L and He, Zhigang and Duan, Xin and Bu, Guojun and Davis, Albert A and Karthik Shekhar and Torre, Anna La and Chan, David C and Canto-Soler, M Valeria and Flanagan, John G and Subramanian, Preeti and Rossi, Sharyn and Brunner, Thomas and Bovenkamp, Diane E and Calkins, David J}
}
@article {1333942,
	title = {Increased bioavailability of cyclic guanylate monophosphate prevents retinal ganglion cell degeneration},
	journal = {Neurobiol Dis},
	volume = {121},
	year = {2019},
	month = {2019 Jan},
	pages = {65-75},
	abstract = {The nitric oxide - guanylyl cyclase-1 - cyclic guanylate monophosphate (NO-GC-1-cGMP) pathway has emerged as a potential pathogenic mechanism for glaucoma, a common intraocular pressure (IOP)-related optic neuropathy characterized by the degeneration of retinal ganglion cells (RGCs) and their axons in the optic nerve. NO activates GC-1 to increase cGMP levels, which are lowered by cGMP-specific phosphodiesterase (PDE) activity. This pathway appears to play a role in both the regulation of IOP, where reduced cGMP levels in mice leads to elevated IOP and subsequent RGC degeneration. Here, we investigated whether potentiation of cGMP signaling could protect RGCs from glaucomatous degeneration. We administered the PDE5 inhibitor tadalafil orally (10 mg/kg/day) in murine models of two forms of glaucoma - primary open angle glaucoma (POAG; GC-1 mice) and primary angle-closure glaucoma (PACG; Microbead Occlusion Model) - and measured RGC viability at both the soma and axon level. To determine the direct effect of increased cGMP on RGCs in vitro, we treated axotomized whole retina and primary RGC cultures with the cGMP analogue 8-Br-cGMP. Tadalafil treatment increased plasma cGMP levels in both models, but did not alter IOP or mean arterial pressure. Nonetheless, tadalafil treatment prevented degeneration of RGC soma and axons in both disease models. Treatment of whole, axotomized retina and primary RGC cultures with 8-Br-cGMP markedly attenuated both necrotic and apoptotic cell death pathways in RGCs. Our findings suggest that enhancement of the NO-GC-1-cGMP pathway protects the RGC body and axon in murine models of POAG and PACG, and that enhanced signaling through this pathway may serve as a novel glaucoma treatment, acting independently of IOP.},
	issn = {1095-953X},
	doi = {10.1016/j.nbd.2018.09.002},
	author = {Wareham, Lauren K and Dordea, Ana C and Schleifer, Grigorij and Yao, Vincent and Batten, Annabelle and Fei, Fei and Mertz, Joseph and Gregory-Ksander, Meredith and Pasquale, Louis R and Buys, Emmanuel S and Sappington, Rebecca M}
}
@article {1623367,
	title = {Impact of Adding Augmented Superior Rectus Transpositions to Medial Rectus Muscle Recessions When Treating Esotropic Moebius Syndrome},
	journal = {Am J Ophthalmol},
	volume = {237},
	year = {2022},
	month = {2022 05},
	pages = {83-90},
	abstract = {PURPOSE: To describe outcomes after treatment of Moebius syndrome (MBS) esotropia by adjustable bilateral medial rectus recession (BMR) with and without augmented superior rectus transposition (SRT). DESIGN: Retrospective case series. METHODS: Patients meeting 2014 diagnostic criteria for MBS and treated at Boston Children{\textquoteright}s Hospital between 2003 and 2019 were identified via billing records and chart review. Visual acuity, sensorimotor evaluations, strabismus procedures, and other clinical features were recorded. Surgical outcomes for patients treated with strabismus surgery (excluding those with prior surgery elsewhere) were evaluated. The primary outcome measure was postoperative alignment comparing treatment by adjustable BMR vs adjustable BMR+SRT. RESULTS: A total of 20 patients had MBS, and 12 of these (60\%) were male. Fifteen patients (75\%) had primary position esotropia, and all had bilateral abduction deficit. Eight of 20 patients met inclusion criteria for primary strabismus surgery outcome. Five had undergone adjustable BMR ranging from 4.5 to 6.5 mm. Three had undergone adjustable BMR+SRT, all with 4-mm medial rectus muscle recessions. Mean preoperative esotropia before treatment by BMR was 39.5 PD ({\textpm} 15 PD) with mean postoperative esotropia 9 PD ({\textpm} 7.9 PD) at 6 months. Mean preoperative esotropia before treatment by BMR+SRT was 70.8 PD ({\textpm} 5.9 PD) with mean postoperative esotropia 2.5 PD ({\textpm} 3.5 PD) at 6 months. Significantly greater reduction in esotropia resulted from BMR+SRT than from BMR (P\&nbsp;=\&nbsp;.036). CONCLUSIONS: BMR proved sufficient to treat esotropia \&lt;50 PD and BMR+SRT for greater esotropia in patients with MBS-associated abduction limitation.},
	keywords = {Child, Esotropia, Female, Humans, Male, Mobius Syndrome, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Retrospective Studies, Strabismus, Treatment Outcome, Vision, Binocular},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.11.006},
	author = {Warkad, Vivekanand U and Hunter, David G and Dagi, Alexander F and MacKinnon, Sarah and Kazlas, Melanie A and Heidary, Gena and Staffa, Steven J and Dagi, Linda R}
}
@article {1626098,
	title = {Lamina cribrosa vessel and collagen beam networks are distinct},
	journal = {Exp Eye Res},
	year = {2021},
	month = {2021 Dec 29},
	pages = {108916},
	abstract = {Our goal was to analyze the spatial interrelation between vascular and collagen networks in the lamina cribrosa (LC). Specifically, we quantified the percentages of collagen beams with/without vessels and of vessels inside/outside of collagen beams. To do this, the vasculature of six normal monkey eyes was labeled by perfusion post-mortem. After enucleation, coronal cryosections through the LC were imaged using fluorescence and polarized light microscopy to visualize the blood vessels and collagen beams, respectively. The images were registered to form 3D volumes. Beams and vessels were segmented, and their spatial interrelationship was quantified in 3D. We found that 22\% of the beams contained a vessel (range 14\%-32\%), and 21\% of vessels were outside beams (13\%-36\%). Stated differently, 78\% of beams did not contain a vessel (68\%-86\%), and 79\% of vessels were inside a beam (64\%-87\%). Individual monkeys differed significantly in the fraction of vessels outside beams (p \&lt; 0.01 by linear mixed effect analysis), but not in the fraction of beams with vessels (p \&gt; 0.05). There were no significant differences between contralateral eyes in the percent of beams with vessels and of vessels outside beams (p \&gt; 0.05). Our results show that the vascular and collagenous networks of the LC in monkey are clearly distinct, and the historical notions that each LC beam contains a vessel and all vessels are within beams are inaccurate. We postulate that vessels outside beams may be relatively more vulnerable to mechanical compression by elevated IOP than are vessels shielded inside of beams.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2021.108916},
	author = {Waxman, Susannah and Brazile, Bryn L and Yang, Bin and Lee, Po-Yi and Hua, Yi and Gogola, Alexandra L and Lam, Po and Voorhees, Andrew P and Rizzo, Joseph F and Jakobs, Tatjana C and Sigal, Ian A}
}
@article {1677776,
	title = {Individual astrocyte morphology in the collagenous lamina cribrosa revealed by multicolor DiOlistic labeling},
	journal = {Exp Eye Res},
	volume = {230},
	year = {2023},
	month = {2023 May},
	pages = {109458},
	abstract = {Astrocytes in the lamina region of the optic nerve head play vital roles in supporting retinal ganglion cell axon health. In glaucoma, these astrocytes are implicated as early responders to stressors, undergoing characteristic changes in cell function as well as cell morphology. Much of what is currently known about individual lamina astrocyte morphology has been learned from rodent models which lack a defining feature of the human optic nerve head, the collagenous lamina cribrosa (LC). Current methods available for evaluation of collagenous LC astrocyte morphology have significant shortcomings. We aimed to evaluate Multicolor DiOlistic labeling (MuDi) as an approach to reveal individual astrocyte morphologies across the collagenous LC. Gold microcarriers were coated with all combinations of three fluorescent cell membrane dyes, DiI, DiD, and DiO, for a total of seven dye combinations. Microcarriers were delivered to 150\&nbsp;μm-thick coronal vibratome slices through the LC of pig, sheep, goat, and monkey eyes via MuDi. Labeled tissues were imaged with confocal and second harmonic generation microscopy to visualize dyed cells and LC collagenous beams, respectively. GFAP labeling of DiOlistically-labeled cells with astrocyte morphologies was used to investigate cell identity. 3D models of astrocytes were created from confocal image stacks for quantification of morphological features. DiOlistic labeling revealed fine details of LC astrocyte morphologies including somas, primary branches, higher-order branches, and end-feet. Labeled cells with astrocyte morphologies were GFAP+. Astrocytes were visible across seven distinct color channels, allowing high labeling density while still distinguishing individual cells from their neighbors. MuDi was capable of revealing tens to hundreds of collagenous LC astrocytes, in situ, with a single application. 3D astrocyte models allowed automated quantification of morphological features including branch number, length, thickness, hierarchy, and straightness as well as Sholl analysis. MuDi labeling provides an opportunity to investigate morphologies of collagenous LC astrocytes, providing both qualitative and quantitative detail, in healthy tissues. This approach may open doors for research of glaucoma, where astrocyte morphological alterations are thought to coincide with key functional changes related to disease progression.},
	keywords = {Animals, Astrocytes, Glaucoma, Humans, Optic Disk, Retinal Ganglion Cells, Sheep, Swine},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2023.109458},
	author = {Waxman, Susannah and Quinn, Marissa and Donahue, Cara and Falo, Louis D and Sun, Daniel and Jakobs, Tatjana C and Sigal, Ian A}
}
@article {1638568,
	title = {Myopic Shift at 10-Year Follow-up in the Infant Aphakia Treatment Study},
	journal = {Ophthalmology},
	volume = {129},
	number = {9},
	year = {2022},
	month = {2022 09},
	pages = {1064-1065},
	keywords = {Aphakia, Aphakia, Postcataract, Cataract Extraction, Follow-Up Studies, Humans, Infant, Myopia},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.04.004},
	author = {Weakley, David R and Nizam, Azhar and VanderVeen, Deborah K and Wilson, M Edward and Kruger, Stacy and Lambert, Scott R and Infant Aphakia Treatment Study Group}
}
@article {1589746,
	title = {A framework for the evaluation of patients with congenital facial weakness},
	journal = {Orphanet J Rare Dis},
	volume = {16},
	number = {1},
	year = {2021},
	month = {2021 Apr 07},
	pages = {158},
	abstract = {There is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.},
	issn = {1750-1172},
	doi = {10.1186/s13023-021-01736-1},
	author = {Webb, Bryn D and Manoli, Irini and Engle, Elizabeth C and Jabs, Ethylin W}
}
@article {1559573,
	title = {A multi-center case series of sarcoid optic neuropathy},
	journal = {J Neurol Sci},
	year = {2020},
	month = {2020 Dec 19},
	pages = {117282},
	abstract = {OBJECTIVE: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes. METHODS: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis. RESULTS: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50\&nbsp;years (range, 17-70\&nbsp;years) and 71\% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68\%) patients had radiologic evidence of other nervous system involvement and 20 (39\%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71\%) patients (median: 14/μL; range: 1-643/μL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67\%); optic nerve/sheath, 9 (18\%); or other nervous system region, 8 (16\%). Forty patients improved with treatment (78\%), 98\% receiving corticosteroids and 65\% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24\%) had a visual acuity of 20/200 or worse at last follow-up. CONCLUSIONS: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.},
	issn = {1878-5883},
	doi = {10.1016/j.jns.2020.117282},
	author = {Webb, Lauren M and Chen, John J and Aksamit, Allen J and Bhattacharyya, Shamik and Chwalisz, Bart K and Balaban, Denis and Manzano, Giovanna S and Ali, Ahya S and Lord, Jennifer and Clardy, Stacey L and Samudralwar, Rohini D and Mao-Draayer, Yang and Garrity, James A and Bhatti, M Tariq and Turner, Lindsey E and Flanagan, Eoin P}
}
@article {1347448,
	title = {Dynasore protects the ocular surface against damaging stress},
	journal = {PLoS One},
	volume = {13},
	number = {10},
	year = {2018},
	month = {2018},
	pages = {e0204288},
	abstract = {Water soluble "vital" dyes are commonly used clinically to evaluate health of the ocular surface; however, staining mechanisms remain poorly understood. Recent evidence suggests that sublethal damage stimulates vital dye uptake by individual living cells. Since cell damage can also stimulate reparative plasma membrane remodeling, we hypothesized that dye uptake occurs via endocytic vesicles. In support of this idea, we show here that application of oxidative stress to relatively undifferentiated monolayer cultures of human corneal epithelial cells stimulates both dye uptake and endocytosis, and that dye uptake is blocked by co-treatment with three different endocytosis inhibitors. Stress application to stratified and differentiated corneal epithelial cell cultures, which are a better model of the ocular surface, also stimulated dye uptake; however, endocytosis was not stimulated, and two of the endocytosis inhibitors did not block dye uptake. The exception was Dynasore and its more potent analogue Dyngo-4a, both small molecules developed to target dynamin family GTPases, but also having off-target effects on the plasma membrane. Significantly, while Dynasore blocked stress-stimulated dye uptake at the ocular surface of ex vivo mouse eyes when treatment was performed at the same time as eyes were stressed, it had no effect when used after stress was applied and the ocular surface was already damaged. Thus, Dynasore could not be working by inhibiting endocytosis. Employing cytotoxicity and western blotting assays, we went on to demonstrate an alternative mechanism. We show that Dynasore is remarkably protective of cells and their surface glycocalyx, preventing damage due to stress, and thus precluding dye entry. These unexpected and novel findings provide greater insight into the mechanisms of vital dye uptake and point the direction for future study. Significantly, they also suggest that Dynasore and its analogues might be used therapeutically to protect the ocular surface and to treat ocular surface disease.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0204288},
	author = {Webster, Andrew and Chintala, Shravan K and Kim, Jasmine and Ngan, Michelle and Itakura, Tatsuo and Panjwani, Noorjahan and Arg{\"u}eso, Pablo and Barr, Joseph T and Jeong, Shinwu and Elizabeth Fini, M}
}
@article {1789061,
	title = {A Functional Magnetic Resonance Imaging Study Using Dynamic Amplitude of Low-Frequency Fluctuation to Assess Brain Activity in Patients with Moyamoya Disease},
	journal = {Brain Connect},
	volume = {13},
	number = {10},
	year = {2023},
	month = {2023 Dec},
	pages = {621-630},
	abstract = {Introduction: The purpose of this study was to monitor and record the dynamic brain activity of patients with moyamoya disease (MMD), as well as to study the relationship between brain abnormalities and presenting clinical features. Methods: A total of 16 patients with MMD (2 males and 14 females) were invited to participate in the study, as were healthy controls (HCs) with the same number and sex ratio. In this study, the dynamic amplitude of low-frequency fluctuation (dALFF) was utilized to assess changes in spontaneous brain activity. Moreover, we also used correlation analysis to study the relationship among the measured mean of dALFF, behavioral performances, and the retinal nerve fiber layer and the Hospital Anxiety and Depression Scale (HADS) score to explore the potential relationship between MMD and anxiety and depression. Results: Our study reveals that in MMD, dALFF levels decreased in the left lingual gyrus, right insula, and occipital lobe. Discussion: In this study, we found and discussed the potential relationship between the abnormal activities in multiple brain regions and related functional network disorders in patients with MMD, as well as the damage to brain regions that process emotion and vision, in the hopes of providing more ideas for the clinical diagnosis and treatment of MMD.},
	keywords = {Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Moyamoya Disease},
	issn = {2158-0022},
	doi = {10.1089/brain.2023.0017},
	author = {Wei, Qian and Wang, Xiao-Yu and Zhang, Li-Juan and Yu, Chen-Yu and Shu, Hui-Ye and Liao, Xu-Lin and Xu, San-Hua and Su, Ting and Kang, Min and Shao, Yi}
}
@article {1318878,
	title = {Neuroinflammation and microglia in glaucoma: time for a paradigm shift},
	journal = {J Neurosci Res},
	volume = {97},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {70-76},
	abstract = {Glaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i.e., normal tension glaucoma (NTG). Interestingly, patients who carry the gain-of-function mutation of the pro-inflammatory gene TBK1 - tumor necrosis factor (TNF) receptor associated factor NF-κB activator (TANK) binding kinase 1 - are at increased risk to develop NTG. This finding suggests a causal link between neuroinflammatory processes and glaucoma. Various studies have reported the presence of neuroinflammatory responses by microglia, astrocytes and other blood-born immune cells in the optic nerve head (ONH) at early stages of experimental glaucoma. Inhibition of certain pro-inflammatory pathways, particularly those associated with microglial activation, appears to be neuroprotective. In this review, we will focus on the inflammatory responses, in particular the proposed roles of microglia, in the pathogenesis of glaucoma.},
	issn = {1097-4547},
	doi = {10.1002/jnr.24256},
	author = {Wei, Xin and Cho, Kin-Sang and Thee, Eric F and Jager, Martine J and Chen, Dong Feng}
}
@article {1364564,
	title = {CRISPR-Cas: to take up DNA or not-that is the question},
	journal = {Cell Host Microbe},
	volume = {12},
	number = {2},
	year = {2012},
	month = {2012 Aug 16},
	pages = {125-6},
	abstract = {Landmark experiments in the 1920s showed that capsule switching is critical for Streptococcus pneumonia survival. Further studies demonstrated that capsule "transformation" occurs via DNA uptake. In this issue of Cell Host and Microbe, Bikard et al. (2012) show that CRISPR-Cas systems inhibit DNA uptake, selecting for the outgrowth of CRISPR-defective pneumococci.},
	issn = {1934-6069},
	doi = {10.1016/j.chom.2012.07.007},
	author = {Weinberger, Ariel D and Gilmore, Michael S}
}
@article {439651,
	title = {A CRISPR View of Cleavage.},
	journal = {Cell},
	volume = {161},
	number = {5},
	year = {2015},
	month = {2015 May 21},
	pages = {964-6},
	abstract = {Seminal studies showed that CRISPR-Cas systems provide adaptive immunity in prokaryotes and\&nbsp;promising gene-editing tools from bacteria to humans. Yet, reports diverged on whether some CRISPR systems naturally target DNA or RNA. Here, Samai and colleagues unify the studies,\&nbsp;showing that a single type III CRISPR-Cas system cleaves both DNA and RNA targets, independently.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2015.05.003},
	author = {Weinberger, Ariel D and Gilmore, Michael S}
}
@article {1364563,
	title = {Viral diversity threshold for adaptive immunity in prokaryotes},
	journal = {MBio},
	volume = {3},
	number = {6},
	year = {2012},
	month = {2012 Dec 04},
	pages = {e00456-12},
	abstract = {UNLABELLED: Bacteria and archaea face continual onslaughts of rapidly diversifying viruses and plasmids. Many prokaryotes maintain adaptive immune systems known as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (Cas). CRISPR-Cas systems are genomic sensors that serially acquire viral and plasmid DNA fragments (spacers) that are utilized to target and cleave matching viral and plasmid DNA in subsequent genomic invasions, offering critical immunological memory. Only 50\% of sequenced bacteria possess CRISPR-Cas immunity, in contrast to over 90\% of sequenced archaea. To probe why half of bacteria lack CRISPR-Cas immunity, we combined comparative genomics and mathematical modeling. Analysis of hundreds of diverse prokaryotic genomes shows that CRISPR-Cas systems are substantially more prevalent in thermophiles than in mesophiles. With sequenced bacteria disproportionately mesophilic and sequenced archaea mostly thermophilic, the presence of CRISPR-Cas appears to depend more on environmental temperature than on bacterial-archaeal taxonomy. Mutation rates are typically severalfold higher in mesophilic prokaryotes than in thermophilic prokaryotes. To quantitatively test whether accelerated viral mutation leads microbes to lose CRISPR-Cas systems, we developed a stochastic model of virus-CRISPR coevolution. The model competes CRISPR-Cas-positive (CRISPR-Cas+) prokaryotes against CRISPR-Cas-negative (CRISPR-Cas-) prokaryotes, continually weighing the antiviral benefits conferred by CRISPR-Cas immunity against its fitness costs. Tracking this cost-benefit analysis across parameter space reveals viral mutation rate thresholds beyond which CRISPR-Cas cannot provide sufficient immunity and is purged from host populations. These results offer a simple, testable viral diversity hypothesis to explain why mesophilic bacteria disproportionately lack CRISPR-Cas immunity. More generally, fundamental limits on the adaptability of biological sensors (Lamarckian evolution) are predicted. IMPORTANCE: A remarkable recent discovery in microbiology is that bacteria and archaea possess systems conferring immunological memory and adaptive immunity. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (CRISPR-Cas) are genomic sensors that allow prokaryotes to acquire DNA fragments from invading viruses and plasmids. Providing immunological memory, these stored fragments destroy matching DNA in future viral and plasmid invasions. CRISPR-Cas systems also provide adaptive immunity, keeping up with mutating viruses and plasmids by continually acquiring new DNA fragments. Surprisingly, less than 50\% of mesophilic bacteria, in contrast to almost 90\% of thermophilic bacteria and Archaea, maintain CRISPR-Cas immunity. Using mathematical modeling, we probe this dichotomy, showing how increased viral mutation rates can explain the reduced prevalence of CRISPR-Cas systems in mesophiles. Rapidly mutating viruses outrun CRISPR-Cas immune systems, likely decreasing their prevalence in bacterial populations. Thus, viral adaptability may select against, rather than for, immune adaptability in prokaryotes.},
	keywords = {Archaea, Bacteria, Computational Biology, Evolution, Molecular, Genetic Loci, Models, Theoretical, Mutation Rate, Recombination, Genetic, Repetitive Sequences, Nucleic Acid},
	issn = {2150-7511},
	doi = {10.1128/mBio.00456-12},
	author = {Weinberger, Ariel D and Wolf, Yuri I and Lobkovsky, Alexander E and Gilmore, Michael S and Koonin, Eugene V}
}
@article {913551,
	title = {Primary open-angle glaucoma.},
	journal = {Nat Rev Dis Primers},
	volume = {2},
	year = {2016},
	month = {2016},
	pages = {16067},
	abstract = {Glaucoma is an optic neuropathy that is characterized by the progressive degeneration of the optic nerve, leading to visual impairment. Glaucoma is the main cause of irreversible blindness worldwide, but typically remains asymptomatic until very severe. Open-angle glaucoma comprises the majority of cases in the United States and western Europe, of which, primary open-angle glaucoma (POAG) is the most common type. By contrast, in China and other Asian countries, angle-closure glaucoma is highly prevalent. These two types of glaucoma are characterized based on the anatomic configuration of the aqueous humour outflow pathway. The pathophysiology of POAG is not well understood, but it is an optic neuropathy that is thought to be associated with intraocular pressure (IOP)-related damage to the optic nerve head and resultant loss of retinal ganglion cells (RGCs). POAG is generally diagnosed during routine eye examination, which includes fundoscopic evaluation and visual field assessment (using perimetry). An increase in IOP, measured by tonometry, is not essential for diagnosis. Management of POAG includes topical drug therapies and surgery to reduce IOP, although new therapies targeting neuroprotection of RGCs and axonal regeneration are under development.},
	issn = {2056-676X},
	doi = {10.1038/nrdp.2016.67},
	author = {Weinreb, Robert N and Leung, Christopher K S and Crowston, Jonathan G and Medeiros, Felipe A and Friedman, David S and Wiggs, Janey L and Martin, Keith R}
}
@article {397886,
	title = {Inhibition of intestinal tumor formation by deletion of the DNA methyltransferase 3a},
	journal = {Oncogene},
	volume = {34},
	number = {14},
	year = {2015},
	month = {2015 Apr 02},
	pages = {1822-30},
	abstract = {Aberrant de novo methylation of DNA is considered an important mediator of tumorigenesis. To investigate the role of de novo DNA methyltransferase 3a (Dnmt3a) in intestinal tumor development, we analyzed the expression of Dnmt3a in murine colon crypts, murine colon adenomas and human colorectal cancer using RNA fluorescence in situ hybridization (FISH), quantitative PCR and immunostaining. Following conditional deletion of Dnmt3a in the colon of APC((Min/+)) mice, we analyzed tumor numbers, genotype of macroadenomas and laser dissected microadenomas, global and regional DNA methylation and gene expression. Our results showed increased Dnmt3a expression in colon adenomas of APC((Min/+)) mice and human colorectal cancer samples when compared with control tissue. Interestingly, in tumor tissue, RNA FISH analysis showed highest Dnmt3a expression in Lgr5-positive stem/progenitor cells. Deletion of Dnmt3a in APC((Min/+)) mice reduced colon tumor numbers by ~40\%. Remaining adenomas and microadenomas almost exclusively contained the non-recombined Dnmt3a allele; no tumors composed of the inactivated Dnmt3a allele were detected. DNA methylation was reduced at the Oct4, Nanog, Tff2 and Cdkn1c promoters and expression of the tumor-suppressor genes Tff2 and Cdkn1c was increased. In conclusion, our results show that Dnmt3a is predominantly expressed in the stem/progenitor cell compartment of tumors and that deletion of Dnmt3a inhibits the earliest stages of intestinal tumor development.},
	keywords = {Adenoma, Animals, Cell Transformation, Neoplastic, Colon, Colorectal Neoplasms, Cyclin-Dependent Kinase Inhibitor p57, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, Gene Expression Regulation, Neoplastic, Homeodomain Proteins, Humans, In Situ Hybridization, Fluorescence, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mucins, Muscle Proteins, Nanog Homeobox Protein, Neoplastic Stem Cells, Octamer Transcription Factor-3, Peptides, Promoter Regions, Genetic, Real-Time Polymerase Chain Reaction, Trefoil Factor-2},
	issn = {1476-5594},
	doi = {10.1038/onc.2014.114},
	author = {Weis, B and Schmidt, J and Maamar, H and Raj, A and Lin, H and T{\'o}th, C and Riedmann, K and Raddatz, G and Seitz, H-K and Ho, A D and Lyko, F and Linhart, H G}
}
@article {1470999,
	title = {Patterns of Pediatric Firearm-Related Ocular Trauma in the United States},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Oct 10},
	abstract = {Importance: Gun violence represents a substantial public health issue, and firearm-related injuries rank second among the causes of injury-related deaths in children aged 0 to 17 years in the United States. Ocular trauma from firearm-related injuries can lead to devastating vision loss, but little is known to date about the specific demographics and characteristics of such injuries in children. Objective: To evaluate the epidemiologic pattern of pediatric firearm-related ocular injuries. Design, Setting, and Participants: This retrospective analysis used deidentified data from the National Trauma Data Bank, the largest national registry of hospitalized trauma cases in the United States. The firearm-related ocular injuries (n = 1972) of pediatric patients (defined as those younger than 21 years) hospitalized between January 1, 2008, and December 31, 2014, were analyzed. Statistical analyses were conducted from July 15, 2017, to June 15, 2019. Exposure: Firearm-related ocular trauma. Main Outcomes and Measures: Pediatric patients with firearm-related ocular injuries were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes and external causes of injury codes. Patient demographics (age, sex, and race/ethnicity), type of ocular injury, injury intent, geographic location, length of hospital admission, health insurance status, disposition at discharge, Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were collected. Results: A total of 8715 firearm-related ocular injuries were identified. Of these injuries, 1972 (22.6\%) occurred in pediatric patients, most of whom were male (1678 [85.1\%]) and adolescents (1037 [52.6\%]), with a mean (SD) age of 15.2 (5) years. Common locations of injury were home (761 [38.6\%]) and street (490 [24.8\%]). Mean (SD) hospital length of stay was 7.6 (12) days, ISS was 16 (13.1), and GCS score was 11 (5.1). The most common types of firearm-related ocular injuries were open wound of the eyeball (820 [41.6\%]) and ocular adnexa (502 [25.5\%]), orbital injuries or fractures (591 [30.0\%]), and contusion of the eye or adnexa (417 [21.1\%]). Patients aged 0 to 3 years had greater odds of unintentional injuries (odds ratio [OR], 4.41; 95\% CI, 2.51-7.75; P \&lt; .001) and injuries occurring at home (OR, 5.39; 95\% CI, 2.81-10.38; P \&lt; .001), and those aged 19 to 21 years had greater odds of assault injuries (OR, 2.17; 95\% CI, 1.77-2.66; P \&lt; .001) and injuries occurring on the street (OR, 1.61; 95\% CI, 1.3-1.98; P \&lt; .001). Black patients had the greatest odds of having injuries with assault intention (OR, 4.53; 95\% CI, 3.68-5.59; P \&lt; .001), and white patients had the greatest likelihood for self-inflicted injury (OR, 7.1; 95\% CI, 5.92-9.51; P \&lt; .001). Traumatic brain injury resulted mostly from self-inflicted trauma (OR, 5.99; 95\% CI, 4.16-8.63; P \&lt; .001), as did visual pathway injuries (OR, 2.86; 95\% CI, 1.95-4.20; P \&lt; .001). The inpatient mortality rate was 12.2\%. Conclusions and Relevance: This study found that pediatric firearm-related ocular injuries from 2008 through 2014 were predominantly sight-threatening and associated with traumatic brain injury. If the possible risk factors, including sex, age, race/ethnicity, and injury intention, can be confirmed for 2015 through 2019, these findings may be useful in developing strategies to prevent pediatric firearm-related ocular injuries.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.3562},
	author = {Weiss, Rebecca and He, Catherine and Gise, Ryan and Parsikia, Afshin and Mbekeani, Joyce N}
}
@article {1806501,
	title = {IC3D Classification of Corneal Dystrophies-Edition 3},
	journal = {Cornea},
	volume = {43},
	number = {4},
	year = {2024},
	month = {2024 Apr 01},
	pages = {466-527},
	abstract = {PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature. METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]. RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table. CONCLUSIONS: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d .},
	keywords = {Corneal Dystrophies, Hereditary, DNA Mutational Analysis, Epithelium, Corneal, Extracellular Matrix Proteins, Humans, Mutation, Pedigree, Phenotype, Transforming Growth Factor beta},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003420},
	author = {Weiss, Jayne S and Rapuano, Christopher J and Seitz, Berthold and Busin, Massimo and Kivel{\"a}, Tero T and Bouheraoua, Nacim and Bredrup, Cecilie and Nischal, Ken K and Chawla, Harshvardhan and Borderie, Vincent and Kenyon, Kenneth R and Kim, Eung Kweon and M{\o}ller, Hans Ulrik and Munier, Francis L and Berger, Tim and Lisch, Walter}
}
@article {382641,
	title = {IC3D classification of corneal dystrophies--edition 2.},
	journal = {Cornea},
	volume = {34},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {117-59},
	abstract = {PURPOSE: To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information. METHODS: The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added. RESULTS: On the basis of revisiting the cellular origin of corneal dystrophy, a modified anatomic classification is proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial-stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. Most of the dystrophy templates are updated. The entity "Epithelial recurrent erosion dystrophies" actually includes a number of potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be differentiated from dystrophies such as TGFBI-induced dystrophies, which are also often associated with recurrent epithelial erosions. The chromosome locus of Thiel-Behnke corneal dystrophy is only located on 5q31. The entity previously designated as a variant of Thiel-Behnke corneal dystrophy on chromosome 10q24 may represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The so-called autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1). Confocal microscopy also has emerged as a helpful tool to reveal in vivo features of several corneal dystrophies that previously required histopathologic examination to definitively diagnose. CONCLUSIONS: This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophies more accurately classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer. Typical histopathologic and confocal images have been added to the corneal dystrophy templates.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000307},
	author = {Weiss, Jayne S and M{\o}ller, Hans Ulrik and Aldave, Anthony J and Seitz, Berthold and Bredrup, Cecilie and Kivel{\"a}, Tero and Munier, Francis L and Rapuano, Christopher J and Nischal, Kanwal K and Kim, Eung Kweon and Sutphin, John and Busin, Massimo and Labb{\'e}, Antoine and Kenyon, Kenneth R and Kinoshita, Shigeru and Lisch, Walter}
}
@article {603901,
	title = {Association of Baseline Visual Acuity and Retinal Thickness With 1-Year Efficacy of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema.},
	journal = {JAMA Ophthalmol},
	year = {2015},
	month = {2015 Nov 25},
	pages = {1-8},
	abstract = {Importance: Comparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment. Objective: To provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography. Design, Setting, and Participants: Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015. Interventions: Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol. Main Outcomes and Measures: One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (>=400 {\textmu}m) or thinner (250 to 399 {\textmu}m) CST. Results: In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64\%), 7 of 31 (23\%), and 21 of 43 (49\%) eyes, respectively. The adjusted differences and 95\% CIs were 39\% (17\% to 60\%) for aflibercept vs bevacizumab, 25\% (5\% to 46\%) for ranibizumab vs bevacizumab, and 13\% (-8\% to 35\%) for aflibercept vs ranibizumab. Conclusions and Relevance: These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients. Trial Registration: clinicaltrials.gov Identifier: NCT01627249.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.4599},
	author = {Wells, John A and Glassman, Adam R and Jampol, Lee M and Aiello, Lloyd Paul and Antoszyk, Andrew N and Baker, Carl W and Bressler, Neil M and Browning, David J and Connor, Crystal G and Elman, Michael J and Ferris, Frederick L and Friedman, Scott M and Melia, Michele and Pieramici, Dante J and Sun, Jennifer K and Beck, Roy W and Diabetic Retinopathy Clinical Research Network}
}
@article {1282161,
	title = {Identification of a Functionally Unique Family of Penicillin-Binding Proteins},
	journal = {J Am Chem Soc},
	volume = {139},
	number = {49},
	year = {2017},
	month = {2017 Dec 13},
	pages = {17727-17730},
	abstract = {Penicillin-binding proteins (PBPs) are enzymes involved in the assembly of the bacterial cell wall, a major target for antibiotics. These proteins are classified by mass into high-molecular-weight PBPs, which are transpeptidases that form peptidoglycan cross-links, and low-molecular-weight PBPs, which are typically hydrolases. We report a functionally unique family of low-molecular-weight PBPs that act as transpeptidases rather than hydrolases, but they do not cross-link peptidoglycan. We show that these PBPs can exchange d-amino acids bearing chemical tags or affinity handles into peptidoglycan precursors, including Lipid II, enabling biochemical studies of proteins involved in cell wall assembly. We report that, in two organisms, the PBPs incorporate lysine into cellular peptidoglycan and that, further, the PBPs have the unprecedented ability to transfer the primary ε-amine of lysine to peptidoglycan.},
	issn = {1520-5126},
	doi = {10.1021/jacs.7b10170},
	author = {Welsh, Michael A and Taguchi, Atsushi and Schaefer, Kaitlin and Van Tyne, Daria and Lebreton, Fran{\c c}ois and Gilmore, Michael S and Kahne, Daniel and Walker, Suzanne}
}
@article {630286,
	title = {Computational assessment of visual search strategies in volumetric medical images.},
	journal = {J Med Imaging (Bellingham)},
	volume = {3},
	number = {1},
	year = {2016},
	month = {2016 Jan},
	pages = {015501},
	abstract = {When searching through volumetric images [e.g., computed tomography (CT)], radiologists appear to use two different search strategies: "drilling" (restrict eye movements to a small region of the image while quickly scrolling through slices), or "scanning" (search over large areas at a given depth before moving on to the next slice). To computationally identify the type of image information that is used in these two strategies, 23 na{\"\i}ve observers were instructed with either "drilling" or "scanning" when searching for target T{\textquoteright}s in 20 volumes of faux lung CTs. We computed saliency maps using both classical two-dimensional (2-D) saliency, and a three-dimensional (3-D) dynamic saliency that captures the characteristics of scrolling through slices. Comparing observers{\textquoteright} gaze distributions with the saliency maps showed that search strategy alters the type of saliency that attracts fixations. Drillers{\textquoteright} fixations aligned better with dynamic saliency and scanners with 2-D saliency. The computed saliency was greater for detected targets than for missed targets. Similar results were observed in data from 19 radiologists who searched five stacks of clinical chest CTs for lung nodules. Dynamic saliency may be superior to the 2-D saliency for detecting targets embedded in volumetric images, and thus "drilling" may be more efficient than "scanning."},
	issn = {2329-4302},
	doi = {10.1117/1.JMI.3.1.015501},
	author = {Wen, Gezheng and Aizenman, Avigael and Drew, Trafton and Wolfe, Jeremy M and Haygood, Tamara Miner and Markey, Mia K}
}
@article {1351210,
	title = {Membrane guanylyl cyclase complexes shape the photoresponses of retinal rods and cones},
	journal = {Front Mol Neurosci},
	volume = {7},
	year = {2014},
	month = {2014},
	pages = {45},
	abstract = {In vertebrate rods and cones, photon capture by rhodopsin leads to the destruction of cyclic GMP (cGMP) and the subsequent closure of cyclic nucleotide gated ion channels in the outer segment plasma membrane. Replenishment of cGMP and reopening of the channels limit the growth of the photon response and are requisite for its recovery. In different vertebrate retinas, there may be as many as four types of membrane guanylyl cyclases (GCs) for cGMP synthesis. Ten neuronal Ca(2+) sensor proteins could potentially modulate their activities. The mouse is proving to be an effective model for characterizing the roles of individual components because its relative simplicity can be reduced further by genetic engineering. There are two types of GC activating proteins (GCAPs) and two types of GCs in mouse rods, whereas cones express one type of GCAP and one type of GC. Mutant mouse rods and cones bereft of both GCAPs have large, long lasting photon responses. Thus, GCAPs normally mediate negative feedback tied to the light-induced decline in intracellular Ca(2+) that accelerates GC activity to curtail the growth and duration of the photon response. Rods from other mutant mice that express a single GCAP type reveal how the two GCAPs normally work together as a team. Because of its lower Ca(2+) affinity, GCAP1 is the first responder that senses the initial decrease in Ca(2+) following photon absorption and acts to limit response amplitude. GCAP2, with a higher Ca(2+) affinity, is recruited later during the course of the photon response as Ca(2+) levels continue to decline further. The main role of GCAP2 is to provide for a timely response recovery and it is particularly important after exposure to very bright light. The multiplicity of GC isozymes and GCAP homologs in the retinas of other vertebrates confers greater flexibility in shaping the photon responses in order to tune visual sensitivity, dynamic range and frequency response.},
	issn = {1662-5099},
	doi = {10.3389/fnmol.2014.00045},
	author = {Wen, Xiao-Hong and Dizhoor, Alexander M and Makino, Clint L}
}
@article {1364565,
	title = {S100B serves as a Ca(2+) sensor for ROS-GC1 guanylate cyclase in cones but not in rods of the murine retina},
	journal = {Cell Physiol Biochem},
	volume = {29},
	number = {3-4},
	year = {2012},
	month = {2012},
	pages = {417-30},
	abstract = {Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca(2+) signal transduction switch. Lowering [Ca(2+)](i) from 200 to 20 nM progressively turns it "ON" as does raising [Ca(2+)](i) from 500 to 5000 nM. The mode operating at lower [Ca(2+)](i) plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca(2+)](i) is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca(2+)-sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K(1/2) for Ca(2+) greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where [Ca(2+)](i) levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in [Ca(2+)](i) in cone outer segments. The findings define a new cone-specific Ca(2+)-dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.},
	keywords = {Animals, Calcium, Cyclic GMP, Enzyme Activation, Guanylate Cyclase, Immunohistochemistry, Light Signal Transduction, Mice, Mice, Knockout, Nerve Growth Factors, Receptors, Cell Surface, Retinal Bipolar Cells, Retinal Cone Photoreceptor Cells, Rod Cell Outer Segment, S100 Calcium Binding Protein beta Subunit, S100 Proteins, Synaptic Membranes},
	issn = {1421-9778},
	doi = {10.1159/000338496},
	author = {Wen, Xiao-Hong and Duda, Teresa and Pertzev, Alexandre and Venkataraman, Venkateswar and Makino, Clint L and Sharma, Rameshwar K}
}
@article {1538310,
	title = {A virtual COVID-19 ophthalmology rotation},
	journal = {Surv Ophthalmol},
	volume = {66},
	number = {2},
	year = {2021},
	month = {2021 Mar-Apr},
	pages = {354-361},
	abstract = {The coronavirus (COVID-19) pandemic temporarily suspended medical student involvement in clinical rotations, resulting in the need to develop virtual clinical experiences. The cancellation of clinical ophthalmology electives and away rotations reduces opportunities for exposure to the field, to network with faculty, conduct research, and prepare for residency applications. We review the literature and discuss the impact and consequences of COVID-19 on undergraduate medical education with an emphasis on ophthalmic undergraduate medical education. We also discuss innovative learning modalities used from medical schools around the world during the COVID-19 pandemic such as virtual didactics, online cases, and telehealth. Finally, we describe a novel, virtual neuro-ophthalmology elective created to educate medical students on neuro-ophthalmology foundational principles, provide research and presentation opportunities, and build relationships with faculty members. These innovative approaches represent a step forward in further improving medical education in ophthalmology during COVID-19 pandemic and beyond.},
	keywords = {COVID-19, Curriculum, Education, Medical, Undergraduate, Humans, Internship and Residency, Ophthalmology, Pandemics, Students, Medical, Telemedicine},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2020.10.001},
	author = {Wendt, Sydney and Abdullah, Zainub and Barrett, Spencer and Daruwalla, Cyrus and Go, Jonathan A and Le, Brandon and Li, Elijah and Livingston, Chelsea and Miller, Matthew and Nakhleh, Lauren and Pecha, Joseph and Pothula, Shravya and Pradhan, Swetak and Sathappan, Varsha and Shah, Alay and Sonuyi, Alan-Michael and Ugoh, Peter and Wang, Qiancheng and Weber, Nicole and Succar, Tony and Blieden, Lauren and Mortensen, Peter and Elkin, Zachary and Sun, Grace and Lee, Andrew G}
}
@article {1470995,
	title = {Unicoronal Synostosis},
	journal = {J Pediatr},
	volume = {213},
	year = {2019},
	month = {2019 Oct},
	pages = {243-243.e1},
	issn = {1097-6833},
	doi = {10.1016/j.jpeds.2019.05.043},
	author = {Weng, Frank and Meara, John G and Dagi, Linda R}
}
@article {1351211,
	title = {Management of pediatric uveitis},
	journal = {F1000Prime Rep},
	volume = {6},
	year = {2014},
	month = {2014},
	pages = {41},
	abstract = {Pediatric uveitis is a topic of special interest not only because of the unique diagnostic and therapeutic challenges but also because of the lifetime burden of vision loss if the problem is not adequately treated, as well as the economic and psychological toll on the family. Often, uveitis in children is discovered as part of a routine eye exam; this silent, insidious inflammation can be difficult to treat and can lead to further complications if not handled skillfully. Corticosteroids have long been the mainstay of therapy; however, the significant associated side effects mandate a corticosteroid-sparing therapeutic regimen in pursuit of remission. In this review, we cover the therapeutic options for pediatric uveitis, specifically focusing on the most common non-infectious varieties, juvenile idiopathic arthritis-associated uveitis and pars planitis.},
	issn = {2051-7599},
	doi = {10.12703/P6-41},
	author = {Wentworth, Bailey A and Freitas-Neto, Clovis A and Foster, C Stephen}
}
@article {303961,
	title = {A clinical, radiologic, and immunopathologic study of five periorbital intraosseous cavernous vascular malformations.},
	journal = {Am J Ophthalmol},
	volume = {158},
	number = {4},
	year = {2014},
	month = {2014 Oct},
	pages = {816-826.e1},
	abstract = {PURPOSE: To correlate the clinical, radiographic, histopathologic, and immunohistochemical features of 5 primary periorbital intraosseous cavernous vascular malformations. DESIGN: Retrospective interventional case series. METHODS: Clinical and operative records and radiographic images were reviewed. Histopathologic slides were evaluated with hematoxylin-eosin, trichrome, and elastin stains. Immunohistochemical studies were performed with a spectrum of monoclonal antibodies directed at antigens of vascular cells. RESULTS: Three men and 2 women ranged in age from 36 to 64 years. Vision was unaffected and there was no proptosis or globe displacement. The slow-growing lesions measured 13-25 mm in greatest diameter (mean 16.4 mm). Computed tomographic studies revealed that 2 lesions were situated in the maxillary bone, 2 in the frontal, and 1 in the zygoma, all anteriorly and with circumscribed, lucent, honeycombed, or sunburst characteristics. Histopathologically the lesions were composed of cavernous or telangiectatic channels; 1 showed advanced fibrotic vascular involution. Immunohistochemistry demonstrated CD31/34 positivity for vascular endothelium and D2-40 negativity for lymphatic endothelium. A typically thin mural myofibroblastic cuff was smooth muscle actin positive, weakly calponin positive, and desmin negative. Glucose transporter-1 and Ki-67 were negative in the endothelium. CONCLUSIONS: Intraosseous vascular lesions resemble orbital cavernous venous malformations (not true hemangiomas), except that their vascular walls are thinner owing to the constraints imposed by neighboring bone spicules, which limit the amount of interstitium from which mural myofibroblasts can be recruited. The bony trabeculae conferred the honeycomb or sunburst appearances observed radiographically. En bloc excision of these lesions was successful and avoided complications (mean follow-up, 46 months).},
	keywords = {Adult, Biological Markers, Female, Humans, Immunoenzyme Techniques, Intervention Studies, Male, Middle Aged, Orbital Diseases, Retrospective Studies, Skull, Spine, Tomography, X-Ray Computed, Vascular Malformations},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2014.07.004},
	author = {Werdich, Xiang Q and Jakobiec, Frederick A and Curtin, Hugh D and Fay, Aaron}
}
@article {1363221,
	title = {A review of advanced genetic testing for clinical prognostication in uveal melanoma},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {361-71},
	abstract = {Uveal melanoma (UM) has a strong propensity to metastasize and the prognosis for metastatic disease is very poor. It has been suggested that occult micrometastases are already present, but undetectable, in many patients at the time when the primary ocular tumor is diagnosed and treated. To identify high-risk patients for close monitoring and early intervention with prophylactic adjuvant systemic therapy, an accurate predictive system is necessary for stratifying those patients at risk of developing metastatic disease. To date, many clinical and histopathological features, molecular pathway characteristics, and genetic fingerprints of UM have been suggested for disease prognostication. Among the newest of them, tumor genetics has received the most attention in demonstrating promise as a prognostic tool. Because of the plethora of recent developments, we summarize and compare in this review the important standard and more advanced cytogenetic prognostic markers. We further describe the variety of genetic tests available for prognostication of UM, and provide a critical assessment of the respective advantages and disadvantages of these tools.},
	keywords = {Biomarkers, Tumor, Cytogenetics, Gene Expression Profiling, Genetic Markers, Genetic Testing, Humans, Melanoma, Prognosis, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Uveal Neoplasms},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825290},
	author = {Werdich, Xiang Q and Jakobiec, Frederick A and Singh, Arun D and Kim, Ivana K}
}
@article {1445352,
	title = {A Review of OCT Angiography in Glaucoma},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Jun 03},
	pages = {1-8},
	abstract = {There is growing evidence that vascular dysfunction plays a role in the pathogenesis of glaucoma. The details of this relationship have remained elusive partially due to limitations in our ability to assess blood flow in the optic nerve. Optical coherence tomography angiography (OCTA) has emerged as a promising new technology well positioned to become the first clinically suitable test of optic nerve perfusion. OCTA uses the motion of red blood cells as an intrinsic contrast agent to create reproducible images of microvascular networks rapidly and non-invasively. A significant body of research regarding the use of OCTA in glaucoma has emerged in recent years. This review aims to provide an overview of the basic principles underlying OCTA technology, summarize the current literature regarding the application of OCTA in the management of glaucoma, and address the role of OCTA in explicating the vascular pathogenesis of glaucoma.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1620807},
	author = {Werner, Astrid C and Shen, Lucy Q}
}
@article {1653595,
	title = {Carbon footprint of the 2021 and 2022 AAPOS annual meetings},
	journal = {J AAPOS},
	year = {2022},
	month = {2022 Sep 09},
	abstract = {The COVID-19 pandemic necessitated a virtual annual meeting of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) in 2021, thus eliminating carbon emissions from travel to and from the planned meeting venue in Boston, Massachusetts. We found that the reduced carbon footprint of the virtual meeting saved 1,282 metric tonnes of CO2 emissions compared with estimated CO2 emissions for travel if the meeting had taken place in person, or 880 metric tonnes relative to the projected emissions associated with the in-person 2022 annual meeting in Scottsdale, Arizona. An entirely virtual or hybrid AAPOS meeting would reduce its environmental footprint and increase the opportunity for national and international participation and education.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.06.002},
	author = {West, Constance E and Hunter, David G}
}
@article {1629461,
	title = {Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity},
	journal = {Cell Rep},
	volume = {38},
	number = {1},
	year = {2022},
	month = {2022 01 04},
	pages = {110191},
	abstract = {How do neuronal subtypes emerge during development? Recent molecular studies have profiled existing neuronal diversity, but neuronal subtype genesis remains elusive. The 15 types of mouse retinal bipolar interneurons are characterized by distinct functions, morphologies, and transcriptional profiles. Here, we develop a comprehensive spatiotemporal map of bipolar subtype genesis in the murine retina. Combining multiplexed detection of 16 RNA markers with timed delivery of 5-ethynyl uridine (EdU) and bromodeoxyuridine (BrdU), we analyze more than 30,000 single cells in full retinal sections to classify all bipolar subtypes and their birthdates. We find that bipolar subtype birthdates are ordered and follow a centrifugal developmental axis. Spatial analysis reveals a striking wave pattern of bipolar subtype birthdates, and lineage analyses suggest clonal restriction on homotypic subtype production. These results inspire a hierarchical developmental model, with ordered subtype genesis within lineages. Our results provide insight into neuronal subtype development and establish a framework for studying subtype diversification.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2021.110191},
	author = {West, Emma R and Lapan, Sylvain W and Lee, Changhee and Kajderowicz, Kathrin M and Li, Xihao and Cepko, Constance L}
}
@article {1351212,
	title = {Displacement of optical centers in over-the-counter readers: a potential cause of diplopia},
	journal = {J AAPOS},
	volume = {18},
	number = {3},
	year = {2014},
	month = {2014 Jun},
	pages = {293-4},
	abstract = {Induced prism in spectacle lenses, which may result from inadvertent displacement of optical centers, may worsen an existing heterophoria or even cause diplopia, yet over-the-counter reading glasses (OTC readers) are not always assessed by clinicians when evaluating patients with diplopia or asthenopia. To gauge the magnitude of this potential problem, we used a focimeter and prescription aligner to assess the frequency and extent of clinically significant manufacturing variations in a random selection of 160 OTC readers. The optical centers were vertically displaced by >=3 mm in 11\%, with a maximum displacement of 7 mm in 1 pair. Average interpupillary distance was 64 mm (range, 58-74.5 mm), with interpupillary distance outside the normal range of 60-70 mm in 5\%. Monocular pupillary distance was asymmetric by >=5 mm in 4\%. A 0.75 D power difference between lenses was measured in one pair of OTC readers. Some OTC readers have misaligned optical centers and other manufacturing defects that are of a magnitude sufficient to exacerbate a heterophoria and cause asthenopia or diplopia.},
	keywords = {Diplopia, Eyeglasses, Humans, Optics and Photonics},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2014.01.008},
	author = {West, Constance E and Hunter, David G}
}
@article {1806536,
	title = {Seeing the Future: A Review of Ocular Therapy},
	journal = {Bioengineering (Basel)},
	volume = {11},
	number = {2},
	year = {2024},
	month = {2024 Feb 13},
	abstract = {Ocular diseases present a unique challenge and opportunity for therapeutic development. The eye has distinct advantages as a therapy target given its accessibility, compartmentalization, immune privilege, and size. Various methodologies for therapeutic delivery in ocular diseases are under investigation that impact long-term efficacy, toxicity, invasiveness, and delivery range. While gene, cell, and antibody therapy and nanoparticle delivery directly treat regions that have been damaged by disease, they can be limited in the duration of the therapeutic delivery and have a focal effect. In contrast, contact lenses and ocular implants can more effectively achieve sustained and widespread delivery of therapies; however, they can increase dilution of therapeutics, which may result in reduced effectiveness. Current therapies either offer a sustained release or a broad therapeutic effect, and future directions should aim toward achieving both. This review discusses current ocular therapy delivery systems and their applications, mechanisms for delivering therapeutic products to ocular tissues, advantages and challenges associated with each delivery system, current approved therapies, and clinical trials. Future directions for the improvement in existing ocular therapies include combination therapies, such as combined cell and gene therapies, as well as AI-driven devices, such as cortical implants that directly transmit visual information to the cortex.},
	issn = {2306-5354},
	doi = {10.3390/bioengineering11020179},
	author = {Whalen, Maiya and Akula, Monica and McNamee, Shannon M and Deangelis, Margaret M and Haider, Neena B}
}
@article {1573115,
	title = {Cell cycle re-entry and arrest in G2/M phase induces senescence and fibrosis in Fuchs Endothelial Corneal Dystrophy},
	journal = {Free Radic Biol Med},
	volume = {164},
	year = {2021},
	month = {2021 Feb 20},
	pages = {34-43},
	abstract = {Fuchs endothelial corneal dystrophy (FECD) is an age-related disease whereby progressive loss of corneal endothelial cells (CEnCs) leads to loss of vision. There is currently a lack of therapeutic interventions as the etiology of the disease is complex, with both genetic and environmental factors. In this study, we have provided further insights into the pathogenesis of the disease, showing a causal relationship between senescence and endothelial-mesenchymal transition (EMT) using in vitro and in vivo models. Ultraviolet A (UVA) light induced EMT and senescence in CEnCs. Senescent cells were arrested in G2/M phase of the cell cycle and responsible for the resulting profibrotic phenotype. Inhibiting ATR signaling and subsequently preventing G2/M arrest attenuated EMT. In vivo, UVA irradiation induced cell cycle re-entry in post mitotic CEnCs, resulting in senescence and fibrosis at 1- and 2-weeks post-UVA. Selectively eliminating senescent cells using the senolytic cocktail of dasatinib and quercetin attenuated UVA-induced fibrosis, highlighting the potential for a new therapeutic intervention for FECD.},
	issn = {1873-4596},
	doi = {10.1016/j.freeradbiomed.2020.12.445},
	author = {White, Tomas L and Deshpande, Neha and Kumar, Varun and Gauthier, Alex G and Jurkunas, Ula V}
}
@article {1635664,
	title = {The impact of occlusion therapy and predictors on amblyopia dose-response relationship},
	journal = {Strabismus},
	volume = {30},
	number = {2},
	year = {2022},
	month = {2022 06},
	pages = {78-89},
	abstract = {This study aimed to calculate the dose-response relationship and predictors of visual acuity (VA) improvement following occlusion therapy at the IWK Health Center Eye Clinic and to add to amblyopia therapy dose-response relationship literature. A retrospective chart review was performed, considering patients who reached an occlusion therapy outcome at the IWK Eye Clinic between 2012 and 2019. The treatment outcome was defined as equal VA or stable VA for three consecutive clinical visits despite reported compliance. Subjective patching hours from parental reports, not prescribed hours, were used for statistical analyses. One hundred and thirty-four patients (66 females and 68 males) ages 2-11\&nbsp;years were included. Results showed a dose-response relationship of 224\&nbsp;hours/0.1logMAR increase in VA and total dose of 1344\&nbsp;hours for full-time occlusion and 504\&nbsp;hours for part-time occlusion was required to reach outcome VA. The fastest VA improvement occurred with younger age at treatment initiation, during the first 4\&nbsp;weeks of treatment, and in patients with strabismic and/or severe amblyopia. Classification of amblyopia, age, VA chart, initial distance VA (amblyopic eye), and treatment dose predicted the hour dose-response relationship. Dose-response relationship was faster in younger participants, in participants with strabismic and severe amblyopia, and during the first month of occlusion. Additionally, by creating a GLM model of dose-response relationship, relationship calculations can be performed. Therefore, an estimated timeline can be developed to allow allocation of clinical resources and to prepare patients for the treatment duration required and possibly increase treatment compliance.},
	keywords = {Amblyopia, Child, Child, Preschool, Female, Humans, Male, Retrospective Studies, Sensory Deprivation, Treatment Outcome, Visual Acuity},
	issn = {1744-5132},
	doi = {10.1080/09273972.2022.2046114},
	author = {White, Emily and Walsh, Leah}
}
@article {1645488,
	title = {The Impact of Occlusion Therapy on Amblyopia Success Outcomes},
	journal = {J Binocul Vis Ocul Motil},
	volume = {72},
	number = {3},
	year = {2022},
	month = {2022 Jul-Sep},
	pages = {183-190},
	abstract = {PURPOSE: The recommended amount of occlusion therapy and amblyopia treatment success rates remains controversial. This study explores rates of occlusion therapy success and attempts to address limitations of previous literature. METHODS: A retrospective chart review was performed on patients with occlusion therapy outcomes from 2012 to 2019. Equal visual acuity (VA) or stable VA for three consecutive clinical visits, despite reported good compliance defined outcome VA. RESULTS: Results showed 90.3\% of subjects obtained outcome distance VA of 0.3logMAR, 76\% >=0.3logMAR, 35\% >=0.2logMAR, and 6\% >=0.1logMAR in the amblyopic eye following treatment. Sixty-nine percent of the study population obtained equal vision following occlusion therapy. Only initial VA (amblyopic eye) and initial interocular visual optotype difference at distance predicted post-treatment success. CONCLUSION: These results support the conclusion that occlusion therapy, both PTO and FTO, can be effective in treating amblyopia when good compliance is maintained based on parental reports of compliance. Additionally, as VA gain was higher than in previous literature, it is important to continue treatment until VA is equal or three consecutive cycles of stable VA are obtained to ensure maximum VA improvement.},
	keywords = {Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Amblyopia, Humans, Retrospective Studies, Sensory Deprivation, Treatment Outcome, Visual Acuity},
	issn = {2576-1218},
	author = {White, Emily and Walsh, Leah}
}
@article {591181,
	title = {Incidence of Stevens-Johnson Syndrome and Chemical Burns to the Eye.},
	journal = {Cornea},
	volume = {34},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {1527-33},
	abstract = {PURPOSE: This population-based observational study was designed to estimate the incidence and distribution of SJS-spectrum (Stevens-Johnson syndrome, toxic epidermal necrolysis, and toxic epidermal Necrolysis/Stevens-Johnson syndrome overlap) and chemical burns (alkali or acid burn of the cornea/conjunctiva) in the United States and extrapolate these numbers to the world. METHODS: All patients evaluated in 961 hospital-based US emergency departments between July 1, 2010, and June 30, 2012 were identified retrospectively using the Nationwide Emergency Department Sample (NEDS) from the Agency for Healthcare Research and Quality. SJS-spectrum and chemical burn cases were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. RESULTS: A mean of 3834 new SJS-spectrum cases per year were identified in the United States, resulting in an incidence rate of 12.35 new cases per million per year. Similarly, a mean of 15,865 new chemical burn cases per year were identified, resulting in an incidence rate of 51.10 new cases per million per year. CONCLUSIONS: If the incidence of SJS-spectrum is approximately uniform the world-over, extrapolation from the US figure would amount to approximately 86,500 new cases per year in the world. Extrapolation of ocular chemical burns to the world is difficult because the incidence and severity are anticipated to be higher in the developing world than in the United States. Still, using a US incidence rate, a minimum of 357,710 burn accidents would be expected to occur worldwide every year; there are presently too few data available to calculate the degree of severity and bilaterality.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000646},
	author = {White, Michelle L and Chodosh, James and Jang, Jisun and Dohlman, Claes}
}
@article {1445326,
	title = {Decreased ACKR3 (CXCR7) function causes oculomotor synkinesis in mice and humans},
	journal = {Hum Mol Genet},
	volume = {28},
	number = {18},
	year = {2019},
	month = {2019 Sep 15},
	pages = {3113-3125},
	abstract = {Oculomotor synkinesis is the involuntary movement of the eyes or eyelids with a voluntary attempt at a different movement. The chemokine receptor CXCR4 and its ligand CXCL12 regulate oculomotor nerve development; mice with loss of either molecule have oculomotor synkinesis. In a consanguineous family with congenital ptosis and elevation of the ptotic eyelid with ipsilateral abduction, we identified a co-segregating homozygous missense variant (c.772G\&gt;A) in ACKR3, which encodes an atypical chemokine receptor that binds CXCL12 and functions as a scavenger receptor, regulating levels of CXCL12 available for CXCR4 signaling. The mutant protein (p.V258M) is expressed and traffics to the cell surface but has a lower binding affinity for CXCL12. Mice with loss of Ackr3 have variable phenotypes that include misrouting of the oculomotor and abducens nerves. All embryos show oculomotor nerve misrouting, ranging from complete misprojection in the midbrain, to aberrant peripheral branching, to a thin nerve, which aberrantly innervates the lateral rectus (as seen in Duane syndrome). The abducens nerve phenotype ranges from complete absence, to aberrant projections within the orbit, to a normal trajectory. Loss of ACKR3 in the midbrain leads to downregulation of CXCR4 protein, consistent with reports that excess CXCL12 causes ligand-induced degradation of CXCR4. Correspondingly, excess CXCL12 applied to ex vivo oculomotor slices causes axon misrouting, similar to inhibition of CXCR4. Thus, ACKR3, through its regulation of CXCL12 levels, is an important regulator of axon guidance in the oculomotor system; complete loss causes oculomotor synkinesis in mice, while reduced function causes oculomotor synkinesis in humans.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddz137},
	author = {Whitman, Mary C and Miyake, Noriko and Nguyen, Elaine H and Bell, Jessica L and Matos Ruiz, Paola M and Chan, Wai-Man and Di Gioia, Silvio Alessandro and Mukherjee, Nisha and Barry, Brenda J and Bosley, T M and Khan, Arif O and Engle, Elizabeth C}
}
@article {1655718,
	title = {TWIST1, a gene associated with Saethre-Chotzen syndrome, regulates extraocular muscle organization in mouse},
	journal = {Dev Biol},
	volume = {490},
	year = {2022},
	month = {2022 10},
	pages = {126-133},
	abstract = {Heterozygous loss of function mutations in TWIST1 cause Saethre-Chotzen syndrome, which is characterized by craniosynostosis, facial asymmetry, ptosis, strabismus, and distinctive ear appearance. Individuals with syndromic craniosynostosis have high rates of strabismus and ptosis, but the underlying pathology is unknown. Some individuals with syndromic craniosynostosis have been noted to have absence of individual extraocular muscles or abnormal insertions of the extraocular muscles on the globe. Using conditional knock-out alleles for Twist1 in cranial mesenchyme, we test the hypothesis that Twist1 is required for extraocular muscle organization and position, attachment to the globe, and/or innervation by the cranial nerves. We examined the extraocular muscles in conditional Twist1 knock-out animals using Twist2-cre and Pdgfrb-cre drivers. Both are expressed in cranial mesoderm and neural crest. Conditional inactivation of Twist1 using these drivers leads to disorganized extraocular muscles that cannot be reliably identified as specific muscles. Tendons do not form normally at the insertion and origin of these dysplastic muscles. Knock-out of Twist1 expression in tendon precursors, using scleraxis-cre, however, does not alter EOM organization. Furthermore, developing motor neurons, which do not express Twist1, display abnormal axonal trajectories in the orbit in the presence of dysplastic extraocular muscles. Strabismus in individuals with TWIST1 mutations may therefore be caused by abnormalities in extraocular muscle development and secondary abnormalities in innervation and tendon formation.},
	keywords = {Acrocephalosyndactylia, Animals, Craniosynostoses, Mice, Neural Crest, Oculomotor Muscles, Strabismus, Twist-Related Protein 1},
	issn = {1095-564X},
	doi = {10.1016/j.ydbio.2022.07.010},
	author = {Whitman, Mary C and Gilette, Nicole M and Bell, Jessica L and Kim, Seoyoung A and Tischfield, Max and Engle, Elizabeth C}
}
@article {1347449,
	title = {Loss of CXCR4/CXCL12 Signaling Causes Oculomotor Nerve Misrouting and Development of Motor Trigeminal to Oculomotor Synkinesis},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {12},
	year = {2018},
	month = {2018 Oct 01},
	pages = {5201-5209},
	abstract = {Purpose: Proper control of eye movements is critical to vision, but relatively little is known about the molecular mechanisms that regulate development and axon guidance in the ocular motor system or cause the abnormal innervation patterns (oculomotor synkinesis) seen in developmental disorders and after oculomotor nerve palsy. We developed an ex vivo slice assay that allows for live imaging and molecular manipulation of the growing oculomotor nerve, which we used to identify axon guidance cues that affect the oculomotor nerve. Methods: Ex vivo slices were generated from E10.5 IslMN-GFP embryos and grown for 24 to 72 hours. To assess for CXCR4 function, the specific inhibitor AMD3100 was added to the culture media. Cxcr4cko/cko:Isl-Cre:ISLMN-GFP and Cxcl12KO/KO:ISLMN-GFP embryos were cleared and imaged on a confocal microscope. Results: When AMD3100 was added to the slice cultures, oculomotor axons grew dorsally (away from the eye) rather than ventrally (toward the eye). Axons that had already exited the midbrain continued toward the eye. Loss of Cxcr4 or Cxcl12 in vivo caused misrouting of the oculomotor nerve dorsally and motor axons from the trigeminal motor nerve, which normally innervate the muscles of mastication, aberrantly innervated extraocular muscles in the orbit. This represents the first mouse model of trigeminal-oculomotor synkinesis. Conclusions: CXCR4/CXCL12 signaling is critical for the initial pathfinding decisions of oculomotor axons and their proper exit from the midbrain. Failure of the oculomotor nerve to innervate its extraocular muscle targets leads to aberrant innervation by other motor neurons, indicating that muscles lacking innervation may secrete cues that attract motor axons.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-25190},
	author = {Whitman, Mary C and Nguyen, Elaine H and Bell, Jessica L and Tenney, Alan P and Gelber, Alon and Engle, Elizabeth C}
}
@article {603861,
	title = {Two unique TUBB3 mutations cause both CFEOM3 and malformations of cortical development.},
	journal = {Am J Med Genet A},
	volume = {170},
	number = {2},
	year = {2016},
	month = {2016 Feb},
	pages = {297-305},
	abstract = {One set of missense mutations in the neuron specific beta tubulin isotype 3 (TUBB3) has been reported to cause malformations of cortical development (MCD), while a second set has been reported to cause isolated or syndromic Congenital Fibrosis of the Extraocular Muscles type 3 (CFEOM3). Because TUBB3 mutations reported to cause CFEOM had not been associated with cortical malformations, while mutations reported to cause MCD had not been associated with CFEOM or other forms of paralytic strabismus, it was hypothesized that each set of mutations might alter microtubule function differently. Here, however, we report two novel de novo heterozygous TUBB3 amino acid substitutions, G71R and G98S, in four patients with both MCD and syndromic CFEOM3. These patients present with moderately severe CFEOM3, nystagmus, torticollis, and developmental delay, and have intellectual and social disabilities. Neuroimaging reveals defective cortical gyration, as well as hypoplasia or agenesis of the corpus callosum and anterior commissure, malformations of hippocampi, thalami, basal ganglia and cerebella, and brainstem and cranial nerve hypoplasia. These new TUBB3 substitutions meld the two previously distinct TUBB3-associated phenotypes, and implicate similar microtubule dysfunction underlying both. {\textcopyright} 2015 Wiley Periodicals, Inc.},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.37362},
	author = {Whitman, Mary C and Andrews, Caroline and Chan, Wai-Man and Tischfield, Max A and Stasheff, Steven F and Brancati, Francesco and Ortiz-Gonzalez, Xilma and Nuovo, Sara and Garaci, Francesco and MacKinnon, Sarah E and Hunter, David G and Grant, P Ellen and Engle, Elizabeth C}
}
@article {1619431,
	title = {TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy},
	journal = {Hum Genet},
	volume = {140},
	number = {12},
	year = {2021},
	month = {2021 Dec},
	pages = {1709-1731},
	abstract = {Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G\&gt;A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.},
	keywords = {Abnormalities, Multiple, Adolescent, Adult, Amino Acid Substitution, Arginine, Child, Child, Preschool, Facial Paralysis, Female, Fibrosis, Histidine, Humans, Infant, Male, Mutation, Ophthalmoplegia, Peripheral Nervous System Diseases, Syndrome, Tubulin, Young Adult},
	issn = {1432-1203},
	doi = {10.1007/s00439-021-02379-9},
	author = {Whitman, Mary C and Barry, Brenda J and Robson, Caroline D and Facio, Flavia M and Van Ryzin, Carol and Chan, Wai-Man and Lehky, Tanya J and Thurm, Audrey and Zalewski, Christopher and King, Kelly A and Brewer, Carmen and Almpani, Konstantinia and Lee, Janice S and Delaney, Angela and FitzGibbon, Edmond J and Lee, Paul R and Toro, Camilo and Paul, Scott M and Abdul-Rahman, Omar A and Webb, Bryn D and Jabs, Ethylin Wang and Moller, Hans Ulrik and Larsen, Dorte Ancher and Antony, Jayne H and Troedson, Christopher and Ma, Alan and Ragnhild, Glad and Wirgenes, Katrine V and Tham, Emma and Kvarnung, Malin and Maarup, Timothy James and MacKinnon, Sarah and Hunter, David G and Collins, Francis S and Manoli, Irini and Engle, Elizabeth C}
}
@article {1528406,
	title = {Recurrent Rare Copy Number Variants Increase Risk for Esotropia},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {61},
	number = {10},
	year = {2020},
	month = {2020 Aug 03},
	pages = {22},
	abstract = {Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 {\texttimes} 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95\% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95\% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95\% CI 5.4-14.9). Overall, 114 cases (7\%) and only 28 controls (0.7\%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia.},
	issn = {1552-5783},
	doi = {10.1167/iovs.61.10.22},
	author = {Whitman, Mary C and Di Gioia, Silvio Alessandro and Chan, Wai-Man and Gelber, Alon and Pratt, Brandon M and Bell, Jessica L and Collins, Thomas E and Knowles, James A and Armoskus, Christopher and Pato, Michele and Pato, Carlos and Shaaban, Sherin and Staffieri, Sandra and MacKinnon, Sarah and Maconachie, Gail D E and Elder, James E and Traboulsi, Elias I and Gottlob, Irene and Mackey, David A and Hunter, David G and Engle, Elizabeth C and Strabismus Genetics Research Consortium}
}
@article {647351,
	title = {Bifocals Fail to Improve Stereopsis Outcomes in High AC/A Accommodative Esotropia.},
	journal = {Ophthalmology},
	volume = {123},
	number = {4},
	year = {2016},
	month = {2016 Apr},
	pages = {690-6},
	abstract = {PURPOSE: To assess whether stereopsis outcomes of patients with accommodative esotropia with high accommodative convergence/accommodation relationship (AC/A) were improved after treatment with bifocal glasses compared with single-vision lenses. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with high AC/A accommodative esotropia; evidence of stereopsis, binocularity (on Worth 4-dot testing), or improvement in near angle with\&nbsp;+3.00 D lenses; and at least 4 years of records available for review, who were seen in the Department of Ophthalmology at Boston Children{\textquoteright}s Hospital between 2006 and 2014. METHODS: Use of bifocal or single-vision glasses. Charts were reviewed retrospectively. Stereopsis was log transformed for statistical analysis. Linear (for stereopsis) or logistic (for surgery) regression was used to control for confounders. MAIN OUTCOME MEASURES: Stereopsis at final follow-up, difference in stereopsis between final and initial visits, and progression to strabismus surgery. Secondary outcomes included final near and distance deviations. RESULTS: Of the 180 patients who met inclusion criteria, 77 used bifocals and 103 used single-vision lenses. Bifocals did not improve stereopsis outcomes compared with single-vision lenses. In both groups, stereopsis was similar at the initial and final visits, with similar improvement in both groups. Children in the bifocal group had a 3.6-fold higher rate of strabismus surgery than children in the single-lens group (P\&nbsp;= 0.04.) Additionally, children in the bifocal group had near deviations 4 PD larger than those with single lenses at final\&nbsp;follow-up, even after controlling for age and initial deviation (P\&nbsp;= 0.02). These results did not change if surgical patients were eliminated or in the subgroup with initial distance deviation of 0 PD in full hyperopic correction. CONCLUSIONS: Despite their widespread use, there is no evidence that bifocals improve outcomes in children with accommodative esotropia with high AC/A. In our retrospective review, children with bifocals had higher\&nbsp;surgical rates and a smaller improvement in near deviation over time. Although our results suggest that eliminating bifocals could reduce the cost and complexity of care while potentially improving quality, prospective, randomized controlled trials are needed to determine whether a change in practice is warranted.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.12.025},
	author = {Whitman, Mary C and MacNeill, Katelyn and Hunter, David G}
}
@article {1651359,
	title = {TWIST1, a gene associated with Saethre-Chotzen syndrome, regulates extraocular muscleorganization in mouse},
	journal = {Dev Biol},
	year = {2022},
	author = {Whitman, MC and Gilette, NM and Bell ,JL and Kim, SA and Tischfield, M and Engle, EC}
}
@article {1598053,
	title = {Axonal Growth Abnormalities Underlying Ocular Cranial Nerve Disorders},
	journal = {Annu Rev Vis Sci},
	volume = {7},
	year = {2021},
	month = {2021 Sep 15},
	pages = {827-850},
	abstract = {Abnormalities in cranial motor nerve development cause paralytic strabismus syndromes, collectively referred to as congenital cranial dysinnervation disorders, in which patients cannot fully move their eyes. These disorders can arise through one of two mechanisms: (a) defective motor neuron specification, usually by loss of a transcription factor necessary for brainstem patterning, or (b) axon growth and guidance abnormalities of the oculomotor, trochlear, and abducens nerves. This review focuses on our current understanding of axon guidance mechanisms in the cranial motor nerves and how disease-causing mutations disrupt axon targeting. Abnormalities of axon growth and guidance are often limited to a single nerve or subdivision, even when the causative gene is ubiquitously expressed. Additionally, when one nerve is absent, its normal target muscles attract other motor neurons. Study of these disorders highlights the complexities of axon guidance and how each population of neurons uses a unique but overlapping set of axon guidance pathways.},
	issn = {2374-4650},
	doi = {10.1146/annurev-vision-093019-114307},
	author = {Whitman, Mary C}
}
@article {1598058,
	title = {Understanding the Role of Blood Vessels in the Neurologic Manifestations of Coronavirus Disease 2019 (COVID-19)},
	journal = {Am J Pathol},
	volume = {191},
	number = {11},
	year = {2021},
	month = {2021 11},
	pages = {1946-1954},
	abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally identified as an outbreak in Wuhan, China, toward the end of 2019 and quickly became a global pandemic, with a large death toll. Originally identified as a respiratory disease, similar to previously discovered SARS and Middle East respiratory syndrome (MERS), concern has since been raised about the effects of SARS-CoV-2 infection on the vasculature. This viral-vascular involvement is of particular concern with regards to the small vessels present in the brain, with mounting evidence demonstrating that SARS-CoV-2 is capable of crossing the blood-brain barrier. Severe symptoms, termed coronavirus disease 2019 (COVID-19), often result in neurologic complications, regardless of patient age. These neurologic complications range from mild to severe across all demographics; however, the long-term repercussions of neurologic involvement on patient health are still unknown.},
	keywords = {Blood Vessels, Blood-Brain Barrier, COVID-19, Humans, Nervous System Diseases, SARS-CoV-2},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.04.017},
	author = {Whitmore, Hannah A B and Kim, Leo A}
}
@article {1549026,
	title = {TNF-α signaling regulates RUNX1 function in endothelial cells},
	journal = {FASEB J},
	volume = {35},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {e21155},
	abstract = {Runt-related transcription factor 1 (RUNX1) acts as a mediator of aberrant retinal angiogenesis and has been implicated in the progression of proliferative diabetic retinopathy (PDR). Patients with PDR, retinopathy of prematurity (ROP), and wet age-related macular degeneration (wet AMD) have been found to have elevated levels of Tumor Necrosis Factor-alpha (TNF-α) in the eye. In fibrovascular membranes (FVMs) taken from patients with PDR RUNX1 expression was increased in the vasculature, while in human retinal microvascular endothelial cells (HRMECs), TNF-α stimulation causes increased RUNX1 expression, which can be modulated by RUNX1 inhibitors. Using TNF-α pathway inhibitors, we determined that in HRMECs, TNF-α-induced RUNX1 expression occurs via JNK activation, while NF-κB and p38/MAPK inhibition did not affect RUNX1 expression. JNK inhibitors were also effective at stopping high D-glucose-stimulated RUNX1 expression. We further linked JNK to RUNX1 through Activator Protein 1 (AP-1) and investigated the JNK-AP-1-RUNX1 regulatory feedback loop, which can be modulated by VEGF. Additionally, stimulation with TNF-α and D-glucose had an additive effect on RUNX1 expression, which was downregulated by VEGF modulation. These data suggest that the downregulation of RUNX1 in conjunction with anti-VEGF agents may be important in future treatments for the management of diseases of pathologic ocular angiogenesis.},
	issn = {1530-6860},
	doi = {10.1096/fj.202001668R},
	author = {Whitmore, Hannah A B and Amarnani, Dhanesh and O{\textquoteright}Hare, Michael and Delgado-Tirado, Santiago and Gonzalez-Buendia, Lucia and An, Miranda and Pedron, Julien and Bushweller, John H and Arboleda-Velasquez, Joseph F and Kim, Leo A}
}
@article {341721,
	title = {Novel Quantitative Assessment of Metamorphopsia in Maculopathy.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2014},
	month = {2014 Nov 18},
	abstract = {Purpose: Patients with macular disease often report experiencing metamorphopsia (visual distortion). Although typically measured with Amsler charts, more objective and quantitative assessments of perceived distortion are desirable to effectively monitor the presence, progression and remediation of visual impairment. Methods: Participants with binocular (n = 33) and monocular (n= 50) maculopathy across seven disease groups, and control participants (n = 10) with no identifiable retinal disease completed a modified Amsler Grid assessment (presented on a computer screen with eye tracking to ensure fixation compliance) and two novel objective measures of metamorphopsia in the central five degrees of visual field. 81\% (67/83) of participants completed a task requiring them to configure eight dots in the shape of a square, and 64\% (32/50) of participants experiencing monocular distortion completed a spatial alignment task using dichoptic stimuli. 10 controls completed all tasks. Results: Horizontal and vertical distortion magnitudes were calculated for each of the three assessments. Distortion magnitudes were significantly higher in patients than controls in all assessments. There was no significant difference in magnitude of distortion across different macular diseases. Among patients, there were no significant correlations between overall magnitude of distortion among any of the three measures and no significant correlations in localized measures of distortion. Conclusions: Three alternative quantifications of monocular spatial distortion in the central visual field generated uncorrelated estimates of visual distortion. It is therefore unlikely that metamorphopsia is caused solely by displacement of photoreceptors in the retina, but instead involves additional top-down information, knowledge about the scene, and perhaps, cortical reorganization.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15394},
	author = {Wiecek, Emily and Lashkari, Kameran and Dakin, Steven and Bex, Peter J}
}
@article {382646,
	title = {A statistical analysis of metamorphopsia in 7106 amsler grids.},
	journal = {Ophthalmology},
	volume = {122},
	number = {2},
	year = {2015},
	month = {2015 Feb},
	pages = {431-3},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.09.006},
	author = {Wiecek, Emily and Lashkari, Kameran and Dakin, Steven C and Bex, Peter}
}
@article {341691,
	title = {Metamorphopsia and letter recognition.},
	journal = {J Vis},
	volume = {14},
	number = {14},
	year = {2014},
	month = {2014},
	abstract = {Acuity is the most commonly used measure of visual function, and reductions in acuity are associated with most eye diseases. Metamorphopsia-a perceived distortion of visual space-is another common symptom of visual impairment and is currently assessed qualitatively using Amsler (1953) charts. In order to quantify the impact of metamorphopsia on acuity, we measured the effect of physical spatial distortion on letter recognition. Following earlier work showing that letter recognition is tuned to specific spatial frequency (SF) channels, we hypothesized that the effect of distortion might depend on the spatial scale of visual distortion just as it depends on the spatial scale of masking noise. Six normally sighted observers completed a 26 alternate forced choice (AFC) Sloan letter identification task at five different viewing distances, and the letters underwent different levels of spatial distortion. Distortion was controlled using spatially band-pass filtered noise that spatially remapped pixel locations. Noise was varied over five spatial frequencies and five magnitudes. Performance was modeled with logistic regression and worsened linearly with increasing distortion magnitude and decreasing letter size. We found that retinal SF affects distortion at midrange frequencies and can be explained with the tuning of a basic contrast sensitivity function, while object-centered distortion SF follows a similar pattern of letter object recognition sensitivity and is tuned to approximately three cycles per letter (CPL). The interaction between letter size and distortion makes acuity an unreliable outcome for metamorphopsia assessment.},
	issn = {1534-7362},
	doi = {10.1167/14.14.1},
	author = {Wiecek, Emily and Dakin, Steven C and Bex, Peter}
}
@article {1364566,
	title = {Effects of peripheral visual field loss on eye movements during visual search},
	journal = {Front Psychol},
	volume = {3},
	year = {2012},
	month = {2012},
	pages = {472},
	abstract = {Natural vision involves sequential eye movements that bring the fovea to locations selected by peripheral vision. How peripheral visual field loss (PVFL) affects this process is not well understood. We examine how the location and extent of PVFL affects eye movement behavior in a naturalistic visual search task. Ten patients with PVFL and 13 normally sighted subjects with full visual fields (FVF) completed 30 visual searches monocularly. Subjects located a 4{\textdegree} {\texttimes} 4{\textdegree} target, pseudo-randomly selected within a 26{\textdegree} {\texttimes} 11{\textdegree} natural image. Eye positions were recorded at 50 Hz. Search duration, fixation duration, saccade size, and number of saccades per trial were not significantly different between PVFL and FVF groups (p \&gt; 0.1). A χ(2) test showed that the distributions of saccade directions for PVFL and FVL subjects were significantly different in 8 out of 10 cases (p \&lt; 0.01). Humphrey Visual Field pattern deviations for each subject were compared with the spatial distribution of eye movement directions. There were no significant correlations between saccade directional bias and visual field sensitivity across the 10 patients. Visual search performance was not significantly affected by PVFL. An analysis of eye movement directions revealed patients with PVFL show a biased directional distribution that was not directly related to the locus of vision loss, challenging feed-forward models of eye movement control. Consequently, many patients do not optimally compensate for visual field loss during visual search.},
	issn = {1664-1078},
	doi = {10.3389/fpsyg.2012.00472},
	author = {Wiecek, Emily and Pasquale, Louis R and Fiser, Jozsef and Dakin, Steven and Bex, Peter J}
}
@article {280936,
	title = {Metamorphopsia and interocular suppression in monocular and binocular maculopathy.},
	journal = {Acta Ophthalmol},
	volume = {93},
	number = {4},
	year = {2015},
	month = {2015 Jun},
	pages = {e318-20},
	issn = {1755-3768},
	doi = {10.1111/aos.12559},
	author = {Wiecek, Emily and Lashkari, Kameran and Dakin, Steven C and Bex, Peter}
}
@article {1439868,
	title = {Age doesn{\textquoteright}t matter much: hybrid visual and memory search is preserved in older adults},
	journal = {Neuropsychol Dev Cogn B Aging Neuropsychol Cogn},
	volume = {27},
	number = {2},
	year = {2020},
	month = {2020 Mar},
	pages = {220-253},
	abstract = {We tested younger and older observers{\textquoteright} attention and long-term memory functions in a "hybrid search" task, in which observers look through visual displays for instances of any of several types of targets held in memory. Apart from a general slowing, search efficiency did not change with age. In both age groups, reaction times increased linearly with the visual set size and logarithmically with the memory set size, with similar relative costs of increasing load (Experiment 1). We replicated the finding and further showed that performance remained comparable between age groups when familiarity cues were made irrelevant (Experiment 2) and target-context associations were to be retrieved (Experiment 3).\&nbsp;Our findings are at variance with theories of cognitive aging that propose age-specific deficits in attention and memory. As hybrid search resembles many real-world searches, our results might be relevant to improve the ecological validity of assessing age-related cognitive decline.},
	issn = {1744-4128},
	doi = {10.1080/13825585.2019.1604941},
	author = {Wiegand, Iris and Wolfe, Jeremy M}
}
@article {1589755,
	title = {Order, please! Explicit sequence learning in hybrid search in younger and older age},
	journal = {Mem Cognit},
	volume = {49},
	number = {6},
	year = {2021},
	month = {2021 Aug},
	pages = {1220-1235},
	abstract = {Sequence learning effects in simple perceptual and motor tasks are largely unaffected by normal aging. However, less is known about sequence learning in more complex cognitive tasks that involve attention and memory processes and how this changes with age. In this study, we examined whether incidental and intentional sequence learning would facilitate hybrid visual and memory search in younger and older adults. Observers performed a hybrid search task, in which they memorized four or 16 target objects and searched for any of those target objects in displays with four or 16 objects. The memorized targets appeared either in a repeating sequential order or in random order. In the first experiment, observers were not told about the sequence before the experiment. Only a subset of younger adults and none of the older adults incidentally learned the sequence. The "learners" acquired explicit knowledge about the sequence and searched faster in the sequence compared to random condition. In the second experiment, observers were told about the sequence before the search task. Both younger and older adults searched faster in sequence blocks than random blocks. Older adults, however, showed this sequence-learning effect only in blocks with smaller target sets. Our findings indicate that explicit sequence knowledge can facilitate hybrid search, as it allows observers to predict the next target and restrict their visual and memory search. In older age, the sequence-learning effect is constrained by load, presumably due to age-related decline in executive functions.},
	issn = {1532-5946},
	doi = {10.3758/s13421-021-01157-2},
	author = {Wiegand, Iris and Westenberg, Erica and Wolfe, Jeremy M}
}
@article {1615220,
	title = {Target value and prevalence influence visual foraging in younger and older age},
	journal = {Vision Res},
	volume = {186},
	year = {2021},
	month = {2021 Sep},
	pages = {87-102},
	abstract = {The prevalence and reward-value of targets have an influence on visual search. The strength of the effect of an item{\textquoteright}s reward-value on attentional selection varies substantially between individuals and is potentially sensitive to aging. We investigated individual and age differences in a hybrid foraging task, in which the prevalence and value of multiple target types was varied. Using optimal foraging theory measures, foraging was more efficient overall in younger than older observers. However, the influence of prevalence and value on target selections was similar across age groups, suggesting that the underlying cognitive mechanisms are preserved in older age. When prevalence was varied but target value was balanced, younger and older observers preferably selected the most frequent target type and were biased to select another instance of the previously selected target type. When value was varied, younger and older observers showed a tendency to select high-value targets, but preferences were more diverse between individuals. When value and prevalence were inversely related, some observers showed particularly strong preferences for high-valued target types, while others showed a preference for high-prevalent, albeit low-value, target types. In younger adults, individual differences in the selection choices correlated with a personality index, suggesting that avoiding selections of low-value targets may be related to reward-seeking behaviour.},
	issn = {1878-5646},
	doi = {10.1016/j.visres.2021.05.001},
	author = {Wiegand, Iris and Wolfe, Jeremy M}
}
@article {1364567,
	title = {The cell and molecular biology of complex forms of glaucoma: updates on genetic, environmental, and epigenetic risk factors},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {5},
	year = {2012},
	month = {2012 May 04},
	pages = {2467-9},
	keywords = {Epigenomics, Gene-Environment Interaction, Glaucoma, Open-Angle, Humans, Risk Factors},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-9483e},
	author = {Wiggs, Janey L}
}
@article {1351213,
	title = {Carrier frequency of CYP1B1 mutations in the United States (an American Ophthalmological Society thesis)},
	journal = {Trans Am Ophthalmol Soc},
	volume = {112},
	year = {2014},
	month = {2014 Jul},
	pages = {94-102},
	abstract = {PURPOSE: CYP1B1 mutations cause autosomal recessive congenital glaucoma. Disease risk assessment for families with CYP1B1 mutations requires knowledge of the population mutation carrier frequency. The purpose of this study is to determine the CYP1B1 mutation carrier frequency in clinically normal individuals residing in the United States. Because CYP1B1 mutations can exhibit variable expressivity, we hypothesize that the mutation carrier frequency is higher than expected. METHODS: Two hundred fifty individuals without glaucoma or a family history of glaucoma were enrolled. CYP1B1 mutations were identified by DNA sequencing, and pathogenicity was estimated by PolyPhen-2 or a previous report of disease causality. RESULTS: Based on the disease frequency (1 in 10,000) and prevalence of CYP1B1-related congenital glaucoma (15\% to 20\%), the frequency of CYP1B1-related congenital glaucoma in the United States is approximately 1 in 50,000. Assuming Hardy-Weinberg equilibrium, the expected CYP1B1 mutation carrier frequency would be 1 in 112, or 0.89\%. Among the 250 study participants, 11 (4.4\%) are carriers of a single pathogenic mutation, representing a carrier frequency of 1 in 22, which is 5.1 times the expected frequency. A higher-than-expected carrier frequency (1 in 33, 3.0\%) was also observed in 4300 white individuals sequenced by the National Heart Lung and Blood Institute Exome Sequencing Project. CONCLUSIONS: Our results show that the CYP1B1 mutation carrier frequency in the US population is between 1 in 22 and 1 in 33, which is 5.1 to 3.4 times the expected frequency. These results suggest that more individuals than expected are carriers of a deleterious CYP1B1 mutation, and that the prevalence of CYP1B1-related disease may be higher than expected.},
	keywords = {Adult, Aged, Cross-Sectional Studies, Cytochrome P-450 CYP1B1, DNA Mutational Analysis, Female, Gene Frequency, Glaucoma, Humans, Male, Middle Aged, Mutation, Prevalence, Prospective Studies, United States},
	issn = {1545-6110},
	author = {Wiggs, Janey L and Langgurth, Anne M and Allen, Keri F}
}
@article {1323946,
	title = {A Role for Clusterin in Exfoliation Syndrome and Exfoliation Glaucoma?},
	journal = {J Glaucoma},
	volume = {27 Suppl 1},
	year = {2018},
	month = {2018 Jul},
	pages = {S61-S66},
	abstract = {The multifunctional protein clusterin (CLU) is a secreted glycoprotein ubiquitously expressed throughout the body, including in the eye. Its primary function is to act as an extracellular molecular chaperone, preventing the precipitation and aggregation of misfolded extracellular proteins. Clusterin is commonly identified at fluid-tissue interfaces, and has been identified in most body fluids. It is a component of exfoliation material, and CLU mRNA is reduced in eyes with exfoliation syndrome compared with controls. SNPs located in the CLU genomic region have been associated with Alzheimer disease (AD) at the genome-wide level and several CLU SNPs located in an apparent regulatory region have been nominally associated with XFS/XFG in Caucasians with European ancestry and in south Indians. Interestingly, clusterin associates with altered elastic fibers in human photoaged skin and prevents UV-induced elastin aggregation in vitro. In light of the known geographic risk factors for XFS/XFG, which could include UV light, investigations of CLU-geographic interactions could be of interest. Future studies investigating rare CLU variation and other complex interactions including gene-gene interactions in XFS/XFG cases and controls may also be fruitful. Although CLU has been considered as a therapeutic target in AD, cancer and dry eye, a role for clusterin in XFS/XFG needs to be better defined before therapeutic approaches involving CLU can be entertained.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000916},
	author = {Wiggs, Janey L and Kang, Jae Hee and Fan, Bao Jian and Levkovitch-Verbin, Hani and Pasquale, Louis R}
}
@article {303886,
	title = {Expression and Regulation of LOXL1 and Elastin-related Genes in Eyes With Exfoliation Syndrome.},
	journal = {J Glaucoma},
	year = {2014},
	month = {2014 Oct-Nov},
	pages = {S62-3},
	abstract = {Variants in LOXL1 are significantly associated with exfoliation syndrome (XFS), however the impact of the associated variants on disease development is not yet understood. Initially the associated missense changes, R141L and G153D, were considered to be pathogenic alleles. Flipping of the risk allele in certain populations for both missense variants provided strong evidence that these missense changes are not biologically significant and suggest that other LOXL1 variant(s), in linkage disequilibrium with these missense variants, predispose to exfoliation syndrome by affecting gene expression or protein function. Several lines of evidence support dysregulation of LOXL1 gene expression as a contributing factor to disease development. First, in the German population the R141L (rs1048661) risk allele reduced LOXL1 expression by 20\%. Second, haplotype analysis identified a risk haplotype that includes including R141L, G153D, as well as a LOXL1 promoter region variant previously shown to reduce gene expression (rs16958477). Third, the LOXL1 risk haplotype influences gene expression induced by disease-associated factors TGF-B1, oxidative stress, UV light and hypoxia. Finally, a LOXL1 null mouse has some features of XFS suggesting that decreased enzyme activity contributes to predisposition to the disease. Collectively, these results suggest that dysregulation of LOXL1 expression is a contributing factor to exfoliation disease development.},
	issn = {1536-481X},
	doi = {10.1097/IJG.0000000000000124},
	author = {Wiggs, Janey L and Pasquale, Louis R}
}
@article {1364568,
	title = {The p53 codon 72 PRO/PRO genotype may be associated with initial central visual field defects in caucasians with primary open angle glaucoma},
	journal = {PLoS One},
	volume = {7},
	number = {9},
	year = {2012},
	month = {2012},
	pages = {e45613},
	abstract = {BACKGROUND: Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg) and the subset of primary open angle glaucoma (POAG) patients with early loss of central visual field. METHODS: Genotypes for the p53 codon 72 polymorphism (Pro/Arg) were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST). The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral). All cases and controls were Caucasian with European ancestry. RESULTS: The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p=2.7 {\texttimes} 10(-5)). We replicated this finding in the GIST cohort (p  =7.3 {\texttimes} 10(-3), and in the pooled sample (p=6.6 {\texttimes} 10(-7)) and in a meta-analysis of both the US and GIST datasets (1.3 {\texttimes} 10(-6), OR 2.17 (1.58-2.98 for the PRO allele). CONCLUSIONS: These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Apoptosis, Case-Control Studies, Codon, Cohort Studies, European Continental Ancestry Group, Female, Genotype, Glaucoma, Open-Angle, Humans, Male, Middle Aged, Proline, Scotoma, Tumor Suppressor Protein p53, Visual Fields},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0045613},
	author = {Wiggs, Janey L and Hewitt, Alex W and Fan, Bao Jian and Wang, Dan Yi and Figueiredo Sena, Dayse R and O{\textquoteright}Brien, Colm and Realini, Anthony and Craig, Jamie E and Dimasi, David P and Mackey, David A and Haines, Jonathan L and Pasquale, Louis R}
}
@article {1351214,
	title = {Disruption of the blood-aqueous barrier and lens abnormalities in mice lacking lysyl oxidase-like 1 (LOXL1)},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {2},
	year = {2014},
	month = {2014 Feb 10},
	pages = {856-64},
	abstract = {PURPOSE: Exfoliation syndrome (ES) is commonly associated with glaucoma, premature cataracts, and other ocular and systemic pathologies. LOXL1 gene variants are significantly associated with ES; however, the role of the protein in ES development remains unclear. The purpose of this study was to characterize the ocular phenotype in Loxl1(-/-) (null) mice. METHODS: Loxl1 null mice and strain-matched controls (C57BL) were evaluated by clinical and histologic analyses. RESULTS: Anterior segment histology showed a pronounced vesiculation of the anterior lens in the null mice. The lesions were subcapsular and in direct apposition with the posterior iris surface. Fluorescein angiography showed increased diffusion of fluorescein into the anterior chamber of the null mice compared with age-matched controls (P = 0.003, two-tailed, unequal variance t-test), suggesting compromise of the blood-aqueous barrier. Intraocular pressure measurements were within the normal range (16.5 {\textpm} 2.0 mm Hg) in null mice up to 1 year of age. Immunohistochemistry showed decreased elastin in the iris and ciliary body in the null mouse compared with controls. CONCLUSIONS: Elimination of LOXL1 in mice impairs the blood-aqueous humor barrier in the ocular anterior segment and causes lens abnormalities consistent with cataract formation, but does not result in deposition of macromolecular material or glaucoma. These results show that mice lacking LOXL1 have some ES features but that complete disease manifestation requires other factors that could be genetic and/or environmental.},
	keywords = {Amino Acid Oxidoreductases, Animals, Anterior Chamber, Blood-Aqueous Barrier, Cataract, Ciliary Body, Elastin, Exfoliation Syndrome, Fluorescein, Fluorescein Angiography, Fluorescent Antibody Technique, Indirect, Fluorescent Dyes, Gene Expression Regulation, Enzymologic, Immunoblotting, Intraocular Pressure, Iris, Lens, Crystalline, Mice, Mice, Inbred C57BL, Microscopy, Immunoelectron, Phenotype, Polymerase Chain Reaction},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-13033},
	author = {Wiggs, Janey L and Pawlyk, Basil and Connolly, Edward and Adamian, Michael and Miller, Joan W and Pasquale, Louis R and Haddadin, Ramez I and Grosskreutz, Cynthia L and Rhee, Douglas J and Li, Tiansen}
}
@article {1363222,
	title = {The NEIGHBOR consortium primary open-angle glaucoma genome-wide association study: rationale, study design, and clinical variables},
	journal = {J Glaucoma},
	volume = {22},
	number = {7},
	year = {2013},
	month = {2013 Sep},
	pages = {517-25},
	abstract = {Primary open-angle glaucoma (POAG) is a common disease with complex inheritance. The identification of genes predisposing to POAG is an important step toward the development of novel gene-based methods of diagnosis and treatment. Genome-wide association studies (GWAS) have successfully identified genes contributing to complex traits such as POAG however, such studies frequently require very large sample sizes, and thus, collaborations and consortia have been of critical importance for the GWAS approach. In this report we describe the formation of the NEIGHBOR consortium, the harmonized case control definitions used for a POAG GWAS, the clinical features of the cases and controls, and the rationale for the GWAS study design.},
	keywords = {Adult, Aged, Aged, 80 and over, Antihypertensive Agents, Case-Control Studies, Cooperative Behavior, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Middle Aged, Research Design, Trabeculectomy},
	issn = {1536-481X},
	doi = {10.1097/IJG.0b013e31824d4fd8},
	author = {Wiggs, Janey L and Hauser, Michael A and Abdrabou, Wael and Allingham, Robert Rand and Budenz, Donald L and Delbono, Elizabeth and Friedman, David S and Kang, Jae H and Gaasterland, Douglas and Gaasterland, Terry and Lee, Richard K and Lichter, Paul R and Loomis, Stephanie and Liu, Yutao and McCarty, Cathy and Medeiros, Felipe A and Moroi, Sayoko E and Olson, Lana M and Realini, Anthony and Richards, Julia E and Rozsa, Frank W and Schuman, Joel S and Singh, Kuldev and Stein, Joshua D and Vollrath, Douglas and Weinreb, Robert N and Wollstein, Gadi and Yaspan, Brian L and Yoneyama, Sachiko and Zack, Don and Zhang, Kang and Pericak-Vance, Margaret and Pasquale, Louis R and Haines, Jonathan L}
}
@article {1364569,
	title = {Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma},
	journal = {PLoS Genet},
	volume = {8},
	number = {4},
	year = {2012},
	month = {2012},
	pages = {e1002654},
	abstract = {Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95\%CI 0.63-0.75], p = 1.86{\texttimes}10$^{-}${\textonesuperior}$^{8}$), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95\%CI 1.21-1.43], p = 3.87{\texttimes}10$^{-}${\textonesuperior}{\textonesuperior}). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95\% CI 0.50-0.67], p = 1.17{\texttimes}10$^{-}${\textonesuperior}{\texttwosuperior}) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95\% CI 0.53-0.72], p = 8.88{\texttimes}10$^{-}${\textonesuperior}$^{0}$). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95\% CI 0.41-0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95\% CI 0.54-1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.},
	keywords = {Alleles, Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 9, Exfoliation Syndrome, Genome-Wide Association Study, Glaucoma, Open-Angle, Homeodomain Proteins, Humans, Nerve Degeneration, Optic Nerve, Polymorphism, Single Nucleotide, RNA, Long Noncoding, RNA, Untranslated, Transforming Growth Factor beta},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1002654},
	author = {Wiggs, Janey L and Yaspan, Brian L and Hauser, Michael A and Kang, Jae H and Allingham, R Rand and Olson, Lana M and Abdrabou, Wael and Fan, Bao J and Wang, Dan Y and Brodeur, Wendy and Budenz, Donald L and Caprioli, Joseph and Crenshaw, Andrew and Crooks, Kristy and Delbono, Elizabeth and Doheny, Kimberly F and Friedman, David S and Gaasterland, Douglas and Gaasterland, Terry and Laurie, Cathy and Lee, Richard K and Lichter, Paul R and Loomis, Stephanie and Liu, Yutao and Medeiros, Felipe A and McCarty, Cathy and Mirel, Daniel and Moroi, Sayoko E and Musch, David C and Realini, Anthony and Rozsa, Frank W and Schuman, Joel S and Scott, Kathleen and Singh, Kuldev and Stein, Joshua D and Trager, Edward H and Vanveldhuisen, Paul and Vollrath, Douglas and Wollstein, Gadi and Yoneyama, Sachiko and Zhang, Kang and Weinreb, Robert N and Ernst, Jason and Kellis, Manolis and Masuda, Tomohiro and Zack, Don and Richards, Julia E and Pericak-Vance, Margaret and Pasquale, Louis R and Haines, Jonathan L}
}
@article {1363223,
	title = {Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma},
	journal = {Clin Genet},
	volume = {84},
	number = {2},
	year = {2013},
	month = {2013 Aug},
	pages = {167-74},
	abstract = {Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome-wide scan for early-onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early-onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early-onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG.},
	keywords = {Adult, Age of Onset, Aged, Animals, Collagen, Collagen Type XVIII, Exons, Female, Genetic Variation, Genotype, Glaucoma, Open-Angle, Humans, Male, Mice, Middle Aged, Pedigree, Polymorphism, Single Nucleotide},
	issn = {1399-0004},
	doi = {10.1111/cge.12176},
	author = {Wiggs, J L and Howell, G R and Linkroum, K and Abdrabou, W and Hodges, E and Braine, C E and Pasquale, L. R. and Hannon, GJ and Haines, J L and John, S W M}
}
@article {1078836,
	title = {Genetics of Glaucoma},
	journal = {Hum Mol Genet},
	year = {2017},
	month = {2017 May 15},
	abstract = {Genetic and genomic studies, including genome-wide association studies (GWAS) have accelerated the discovery of genes contributing to glaucoma, the leading cause of irreversible blindness world-wide. Glaucoma can occur at all ages, with Mendelian inheritance typical for rare early onset disease (before age 40) and complex inheritance evident in common adult-onset forms of disease. Recent studies have suggested possible therapeutic targets for some patients with early-onset glaucoma based on the molecular and cellular events caused by MYOC, OPTN and TBK1 mutations. Diagnostic genetic tests using early-onset glaucoma genes are also proving useful for pre-symptomatic disease detection and genetic counseling. Recent GWAS completed for three types of common adult-onset glaucoma have identified novel loci for POAG (primary-open-angle glaucoma) (ABCA1, AFAP1, GMDS, PMM2, TGFBR3, FNDC3B, ARHGEF12, GAS7, FOXC1, ATXN2, TXNRD2); PACG (primary angle-closure glaucoma (EPDR1, CHAT, GLIS3, FERMT2, DPM2-FAM102); and exfoliation syndrome (XFS) glaucoma (CACNA1A). In total sixteen genomic regions have been associated with POAG (including the normal tension glaucoma (NTG) subgroup), 8 with PACG and 2 with XFS. These studies are defining important biological pathways and processes that contribute to disease pathogenesis.},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddx184},
	author = {Wiggs, Janey L and Pasquale, Louis R}
}
@article {1125416,
	title = {TFOS DEWS II Tear Film Report},
	journal = {Ocul Surf},
	volume = {15},
	number = {3},
	year = {2017},
	month = {2017 Jul},
	pages = {366-403},
	abstract = {The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2017.03.006},
	author = {Willcox, Mark D P and Arg{\"u}eso, Pablo and Georgiev, Georgi A and Holopainen, Juha M and Laurie, Gordon W and Millar, Tom J and Papas, Eric B and Rolland, Jannick P and Schmidt, Tannin A and Stahl, Ulrike and Suarez, Tatiana and Subbaraman, Lakshman N and U{\c c}akhan, Om{\"u}r {\"O} and Jones, Lyndon}
}
@article {1532355,
	title = {Axon Regeneration in the Mammalian Optic Nerve},
	journal = {Annu Rev Vis Sci},
	volume = {6},
	year = {2020},
	month = {2020 Sep 15},
	pages = {195-213},
	abstract = {The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.},
	issn = {2374-4650},
	doi = {10.1146/annurev-vision-022720-094953},
	author = {Williams, Philip R and Benowitz, Larry I and Goldberg, Jeffrey L and He, Zhigang}
}
@article {1593844,
	title = {Mucopolysaccharidosis Type I-Associated Corneal Disease: A Clinicopathologic Study},
	journal = {Am J Ophthalmol},
	volume = {231},
	year = {2021},
	month = {2021 Nov},
	pages = {39-47},
	abstract = {PURPOSE: To report the anterior segment clinical features and histopathologic and histochemical characteristics of explanted corneas from the largest reported cohort of patients with Hurler syndrome and other variants of mucopolysaccharidosis (MPS) I undergoing corneal transplantation. DESIGN: Retrospective observational case series. METHODS: This institutional study reviewed 15 corneas from 9 patients with MPS I spectrum disease who underwent corneal transplant to treat corneal clouding between May 2011 and October 2020. We reviewed the clinical data, hematoxylin-eosin-stained sections, and histochemical stains, including those for mucopolysaccharides (Alcian blue and/or colloidal iron). The main outcome measures were pathology observed under light microscopy and postsurgical clinical outcomes. RESULTS: Nine patients underwent 15 corneal transplants for corneal clouding (14/15 procedures were deep anterior lamellar keratoplasty). All corneas had mucopolysaccharide deposition visible on hematoxylin-eosin-stained sections, which was highlighted in blue with histochemical stains. All corneas also showed alterations in Bowman{\textquoteright}s layer and the majority also showed epithelial abnormalities. CONCLUSION: MPS I shows significant corneal clouding that is successfully treated with deep anterior lamellar keratoplasty. The excised corneas show characteristic epithelial changes, disruption or breaks in Bowman{\textquoteright}s membrane, and amphophilic collections of stromal granular mucopolysaccharides which are visible on hematoxylin-eosin-stained sections and highlighted by special histochemical stains (Alcian blue and collodial iron). These changes, although subtle, should alert the pathologist to the possibility of an underlying lysosomal storage disorder.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.05.014},
	author = {Williams, Imani M and Pineda, Roberto and Neerukonda, Vamsee K and Stagner, Anna M}
}
@article {1435424,
	title = {ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder},
	journal = {Genet Med},
	volume = {21},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {2103-2115},
	abstract = {PURPOSE: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. METHODS: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. RESULTS: We found the heterozygous missense variant in the ɑ-kinase gene, ALPK1, (c.710C\&gt;T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. CONCLUSION: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.},
	issn = {1530-0366},
	doi = {10.1038/s41436-019-0476-3},
	author = {Williams, Lloyd B and Javed, Asif and Sabri, Amin and Morgan, Denise J and Huff, Chad D and Grigg, John R and Heng, Xiu Ting and Khng, Alexis J and Hollink, Iris H I M and Morrison, Margaux A and Owen, Leah A and Anderson, Katherine and Kinard, Krista and Greenlees, Rebecca and Novacic, Danica and Nida Sen, H and Zein, Wadih M and Rodgers, George M and Vitale, Albert T and Haider, Neena B and Hillmer, Axel M and Ng, Pauline C and Ng, Pauline C and Cheng, Anson and Zheng, Linda and Gillies, Mark C and van Slegtenhorst, Marjon and van Hagen, P Martin and Missotten, Tom O A R and Farley, Gary L and Polo, Michael and Malatack, James and Curtin, Julie and Martin, Frank and Arbuckle, Susan and Alexander, Stephen I and Chircop, Megan and Davila, Sonia and Digre, Kathleen B and Jamieson, Robyn V and Deangelis, Margaret M}
}
@article {1635650,
	title = {Reply to Comment on: Mucopolysaccharidosis type I associated corneal disease: A clinicopathologic study},
	journal = {Am J Ophthalmol},
	volume = {235},
	year = {2022},
	month = {2022 Mar},
	pages = {334-335},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.10.011},
	author = {Williams, Imani M and Pineda, Roberto and Neerukonda, Vamsee K and Stagner, Anna M}
}
@article {1059846,
	title = {Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure},
	journal = {Doc Ophthalmol},
	volume = {134},
	number = {2},
	year = {2017},
	month = {2017 Apr},
	pages = {111-128},
	abstract = {PURPOSE: To compare diagnostic performance and structure-function correlations of multifocal electroretinogram (mfERG), full-field flash ERG (ff-ERG) photopic negative response (PhNR) and transient pattern-reversal ERG (PERG) in a non-human primate (NHP) model of experimental glaucoma (EG). METHODS: At baseline and after induction of chronic unilateral IOP elevation, 43 NHP had alternating weekly recordings of retinal nerve fiber layer thickness (RNFLT) by spectral domain OCT (Spectralis) and retinal function by mfERG (7F slow-sequence stimulus, VERIS), ff-ERG (red 0.42 log cd-s/m(2) flashes on blue 30 scotopic cd/m(2) background, LKC UTAS-E3000), and PERG (0.8{\textdegree} checks, 99\% contrast, 100\&nbsp;cd/m(2) mean, 5\&nbsp;reversals/s, VERIS). All NHP were followed at least until HRT-confirmed optic nerve head posterior deformation, most to later stages. mfERG responses were filtered into low- and high-frequency components (LFC, HFC, \&gt;75\&nbsp;Hz). Peak-to-trough amplitudes of LFC features (N1, P1, N2) and HFC RMS amplitudes were measured and ratios calculated for HFC:P1 and N2:P1. ff-ERG parameters included A-wave (at 10\&nbsp;ms), B-wave (trough-to-peak) and PhNR (baseline-to-trough) amplitudes as well as PhNR:B-wave ratio. PERG parameters included P50 and N95 amplitudes as well as N95:P50 ratio and N95 slope. Diagnostic performance of retinal function parameters was compared using the area under the receiver operating characteristic curve (A-ROC) to discriminate between EG and control eyes. Correlations to RNFLT were compared using Steiger{\textquoteright}s test. RESULTS: Study duration was 15\&nbsp;{\textpm}\&nbsp;8\&nbsp;months. At final follow-up, structural damage in EG eyes measured by RNFLT ranged from 9\% above baseline (BL) to 58\% below BL; 29/43 EG eyes (67\%) and 0/43 of the fellow control eyes exhibited significant (\&gt;7\%) loss of RNFLT from BL. Using raw parameter values, the largest A-ROC findings for mfERG were: HFC (0.82) and HFC:P1 (0.90); for ff-ERG: PhNR (0.90) and PhNR:B-wave (0.88) and for PERG: P50 (0.64) and N95 (0.61). A-ROC increased when data were expressed as \% change from BL, but the pattern of results persisted. At 95\% specificity, the diagnostic sensitivity of mfERG HFC:P1 ratio was best, followed by PhNR and PERG. The correlation to RNFLT was stronger for mfERG HFC (R\&nbsp;=\&nbsp;0.65) than for PhNR (R\&nbsp;=\&nbsp;0.59) or PERG N95 (R\&nbsp;=\&nbsp;0.36), (p\&nbsp;=\&nbsp;0.20, p\&nbsp;=\&nbsp;0.0006, respectively). The PhNR flagged a few EG eyes at the final time point that had not been flagged by mfERG HFC or PERG. CONCLUSIONS: Diagnostic performance and structure-function correlation were strongest for mfERG HFC as compared with ff-ERG PhNR or PERG in NHP EG.},
	issn = {1573-2622},
	doi = {10.1007/s10633-017-9578-x},
	author = {Wilsey, Laura and Gowrisankaran, Sowjanya and Cull, Grant and Hardin, Christy and Burgoyne, Claude F and Fortune, Brad}
}
@article {1504061,
	title = {Accuracy of Autorefraction in Children: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {127},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {1259-1267},
	abstract = {PURPOSE: The purpose of this assessment is to evaluate the accuracy of autorefraction compared with cycloplegic retinoscopy in children. METHODS: Literature searches were last conducted in October 2019 in the PubMed and the Cochrane Library databases for studies published in English. The combined searches yielded 118 citations, of which 53 were reviewed in full text. Of these, 31 articles were deemed appropriate for inclusion in this assessment and subsequently assigned a level of evidence rating by the panel methodologists. Four articles were rated level I, 11 were rated level II, and 16 were rated level III articles. The 16 level III articles were excluded from this review. RESULTS: Thirteen of the 15 studies comparing cycloplegic autorefraction with cycloplegic retinoscopy found a mean difference in spherical equivalent or sphere of less than 0.5 diopters (D); most were less than 0.25 D. Even lower mean differences were found when evaluating the cylindrical component of cycloplegic autorefraction versus cycloplegic retinoscopy. Despite low mean variability, there was significant individual measurement variability; the 95\% limits of agreement were wide and included clinically relevant differences. Comparisons of noncycloplegic with cycloplegic autorefractions found that noncyloplegic refraction tends to over minus by 1 to 2 D. CONCLUSIONS: Cycloplegic autorefraction is appropriate to use in pediatric population-based studies. Cycloplegic retinoscopy can be valuable in individual clinical cases to confirm the accuracy of cycloplegic autorefraction, particularly when corrected visual acuity is worse than expected or the autorefraction results are not consistent with expected findings.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.03.004},
	author = {Wilson, Lorri B and Melia, Michele and Kraker, Raymond T and VanderVeen, Deborah K and Hutchinson, Amy K and Pineles, Stacy L and Galvin, Jennifer A and Lambert, Scott R}
}
@article {836996,
	title = {Difluprednate versus prednisolone acetate for inflammation following cataract surgery in pediatric patients: a randomized safety and efficacy study.},
	journal = {Eye (Lond)},
	volume = {30},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1187-94},
	abstract = {PurposeTo evaluate safety and efficacy of difluprednate 0.05\% ophthalmic emulsion for treatment of postoperative inflammation after cataract surgery in pediatric patients.MethodsThis was a phase 3B, multicentre, randomized, double-masked, active-controlled study of patients aged 0-3 years who underwent uncomplicated cataract surgery in one eye, with/without intraocular lens implantation. Patients were randomized to receive difluprednate 0.05\% four times daily or prednisolone acetate 1\% for 14 days post surgery, followed by tapering for 14 days. Safety included evaluation of adverse events. Primary efficacy was the proportion of patients with an anterior cell grade of 0 (no cells) at day 14; secondary efficacy was a global inflammation score.ResultsForty patients were randomized to each treatment group. Adverse drug reactions included corneal oedema (difluprednate 0.5\%, n=1; prednisolone acetate 1\%, n=0) and increased intraocular pressure or ocular hypertension (n=2/group). Mean intraocular pressure values during treatment were 2-3 mm Hg higher with difluprednate 0.05\% compared with prednisolone acetate 1\%; mean values were similar between groups by the first week after treatment cessation. At 2 weeks post surgery, the incidence of complete clearing of anterior chamber cells was similar between groups (difluprednate 0.05\%, n=30 (78.9\%); prednisolone acetate 1\%, n=31 (77.5\%). Compared with prednisolone acetate 1\%, approximately twice as many difluprednate 0.05\%-treated patients had a global inflammation assessment score indicating no inflammation on day 1 (n=12 (30.8\%) vs n=7 (17.5\%) and day 8 (n=18 (48.7\%) vs n=10 (25.0\%).ConclusionsDifluprednate 0.05\% four times daily showed safety and efficacy profiles similar to prednisolone acetate 1\% four times daily in children 0-3 years undergoing cataract surgery.},
	issn = {1476-5454},
	doi = {10.1038/eye.2016.132},
	author = {Wilson, M E and O{\textquoteright}Halloran, H and VanderVeen, D and Roarty, J and Plager, D A and Markwardt, K and Gedif, K and Lambert, S R}
}
@article {1528397,
	title = {Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease},
	journal = {BMC Med Genomics},
	volume = {13},
	number = {1},
	year = {2020},
	month = {2020 Aug 26},
	pages = {120},
	abstract = {BACKGROUND: Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD. METHODS: To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for \&gt; 170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants. RESULTS: Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (P\&nbsp;\&lt; 5 {\texttimes} 10), (ii) one previously suggested locus with experiment-wise significance (P\&nbsp;\&lt; 0.05/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (near ARMS2/HTRA1, CFH, C2, C3, CETP, TNFRSF10A, VEGFA, APOE), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggested CD46 and TYR as the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement/lipid pathways versus extracellular matrix metabolism). CONCLUSIONS: Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.},
	issn = {1755-8794},
	doi = {10.1186/s12920-020-00760-7},
	author = {Winkler, Thomas W and Grassmann, Felix and Brandl, Caroline and Kiel, Christina and G{\"u}nther, Felix and Strunz, Tobias and Weidner, Lorraine and Zimmermann, Martina E and Korb, Christina A and Poplawski, Alicia and Schuster, Alexander K and M{\"u}ller-Nurasyid, Martina and Peters, Annette and Rauscher, Franziska G and Tobias Elze and Horn, Katrin and Scholz, Markus and Ca{\~n}adas-Garre, Marisa and McKnight, Amy Jayne and Quinn, Nicola and Hogg, Ruth E and K{\"u}chenhoff, Helmut and Heid, Iris M and Stark, Klaus J and Weber, Bernhard H F}
}
@article {1573112,
	title = {MRI Characteristics of NMO, MOG and MS Related Optic Neuritis},
	journal = {Semin Ophthalmol},
	year = {2021},
	month = {2021 Jan 04},
	pages = {1-10},
	abstract = {Acute isolated optic neuritis can be the initial presentation of demyelinating inflammatory central nervous system disease related to multiple sclerosis (MS), neuromyelitis optica (NMO) or myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). In addition to the well-characterized brain and spinal cord imaging features, important and characteristic differences in the radiologic appearance of the optic nerves in these disorders are being described, and magnetic resonance imaging (MRI) of the optic nerves is becoming an essential tool in the differential diagnosis of optic neuritis. Whereas typical demyelinating optic neuritis is a relatively mild and self-limited disease, atypical optic neuritis in NMO and MOG-AD is potentially much more vision-threatening and merits a different treatment approach. Thus, differentiation based on MRI features may be particularly important during the first attack of optic neuritis, when antibody status is not yet known. This review discusses the optic nerve imaging in the major demyelinating disorders with an emphasis on clinically relevant differences that can help clinicians assess and manage these important neuro-ophthalmic disorders. It also reviews the utility of optic nerve MRI as a prognostic indicator in acute optic neuritis.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2020.1866027},
	author = {Winter, Aaron and Chwalisz, Bart}
}
@article {1615210,
	title = {Axon Regeneration: A Subcellular Extension in Multiple Dimensions},
	journal = {Cold Spring Harb Perspect Biol},
	volume = {14},
	number = {3},
	year = {2022},
	month = {2022 03 01},
	abstract = {Axons are a unique cellular structure that allows for the communication between neurons. Axon damage compromises neuronal communications and often leads to functional deficits. Thus, developing strategies that promote effective axon regeneration for functional restoration is highly desirable. One fruitful approach is to dissect the regenerative mechanisms used by some types of neurons in both mammalian and nonmammalian systems that exhibit spontaneous regenerative capacity. Additionally, numerous efforts have been devoted to deciphering the barriers that prevent successful axon regeneration in the most regeneration-refractory system-the adult mammalian central nervous system. As a result, several regeneration-promoting strategies have been developed, but significant limitations remain. This review is aimed to summarize historic progression and current understanding of this exciting yet incomplete endeavor.},
	issn = {1943-0264},
	doi = {10.1101/cshperspect.a040923},
	author = {Winter, Carla C and He, Zhigang and Jacobi, Anne}
}
@article {1789046,
	title = {A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons},
	journal = {Nature},
	volume = {624},
	number = {7991},
	year = {2023},
	month = {2023 Dec},
	pages = {403-414},
	abstract = {The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for {\textquoteright}gain setting{\textquoteright} of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.},
	keywords = {Animals, Brain, Cerebellum, Cerebral Cortex, Electrophysiology, Gene Expression Profiling, Hypothalamus, Mesencephalon, Mice, Neural Pathways, Neurons, Neuropeptides, Neurotransmitter Agents, Reticular Formation, Spinal Cord},
	issn = {1476-4687},
	doi = {10.1038/s41586-023-06817-8},
	author = {Winter, Carla C and Jacobi, Anne and Su, Junfeng and Chung, Leeyup and van Velthoven, Cindy T J and Yao, Zizhen and Lee, Changkyu and Zhang, Zicong and Yu, Shuguang and Gao, Kun and Duque Salazar, Geraldine and Kegeles, Evgenii and Zhang, Yu and Tomihiro, Makenzie C and Zhang, Yiming and Yang, Zhiyun and Zhu, Junjie and Tang, Jing and Song, Xuan and Donahue, Ryan J and Wang, Qing and McMillen, Delissa and Kunst, Michael and Wang, Ning and Smith, Kimberly A and Romero, Gabriel E and Frank, Michelle M and Krol, Alexandra and Kawaguchi, Riki and Geschwind, Daniel H and Feng, Guoping and Goodrich, Lisa V and Liu, Yuanyuan and Tasic, Bosiljka and Hongkui Zeng and He, Zhigang}
}
@article {504076,
	title = {Novel Therapy to Treat Corneal Epithelial Defects: A Hypothesis with Growth Hormone.},
	journal = {Ocul Surf},
	volume = {13},
	number = {3},
	year = {2015},
	month = {2015 Jul},
	pages = {204-212.e1},
	abstract = {Impaired corneal wound healing that occurs with ocular surface disease, trauma, systemic disease, or surgical intervention can lead to persistent corneal epithelial defects (PCED), which result in corneal scarring, ulceration, opacification, corneal neovascularization, and, ultimately, visual compromise and vision loss. The current standard of care can include lubricants, ointments, bandage lenses, amniotic membranes, autologous serum eye drops, and corneal transplants. Various inherent problems exist with application and administration of these treatments, which often may not result in a completely healed surface. A topically applicable compound capable of promoting corneal epithelial cell proliferation and/or migration would be ideal to accelerate healing. We hypothesize that human growth hormone (HGH) is such a compound. In a recent study, HGH was shown to activate signal transducer and activators of transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial migration in a co-culture system of corneal epithelial cells and fibroblasts. These effects require an intact communication between corneal epithelia and fibroblasts. Further, HGH promotes corneal wound healing in a rabbit debridement model, thus demonstrating the effectiveness of HGH in\&nbsp;vivo as well. In conclusion, HGH may represent an exciting and effective topical therapeutic to promote corneal wound healing.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2014.12.005},
	author = {Wirostko, Barbara and Rafii, MaryJane and Sullivan, David A and Morelli, Julia and Ding, Juan}
}
@article {1445349,
	title = {A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease},
	journal = {Ophthalmology},
	volume = {126},
	number = {6},
	year = {2019},
	month = {2019 Jun},
	pages = {792-800},
	abstract = {PURPOSE: To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1\% and 0.05\% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy. DESIGN: An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator. PARTICIPANTS: Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05\%, n\&nbsp;= 51; CyclASol 0.1\%, n\&nbsp;= 51; vehicle, n\&nbsp;= 52, and Restasis, n\&nbsp;= 53). METHODS: After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks. MAIN OUTCOME MEASURES: The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P \&lt; 0.1, central corneal staining P \&lt; 0.001, conjunctival staining P \&lt; 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P \&lt; 0.01). The numbers of ocular adverse events were low in all treatment groups. CONCLUSIONS: CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.01.024},
	author = {Wirta, David L and Torkildsen, Gail L and Moreira, Helen R and Lonsdale, John D and Ciolino, Joseph B and Jentsch, Garrit and Beckert, Michael and Ousler, George W and Steven, Philipp and Kr{\"o}sser, Sonja}
}
@article {1615203,
	title = {Hallmarks of lens aging and cataractogenesis},
	journal = {Exp Eye Res},
	volume = {210},
	year = {2021},
	month = {2021 09},
	pages = {108709},
	abstract = {Lens homeostasis and transparency are dependent on the function and intercellular communication of its epithelia. While the lens epithelium is uniquely equipped with functional repair systems to withstand reactive oxygen species (ROS)-mediated oxidative insult, ROS are not necessarily detrimental to lens cells. Lens aging, and the onset of pathogenesis leading to cataract share an underlying theme; a progressive breakdown of oxidative stress repair systems driving a pro-oxidant shift in the intracellular environment, with cumulative ROS-induced damage to lens cell biomolecules leading to cellular dysfunction and pathology. Here we provide an overview of our current understanding of the sources and essential functions of lens ROS, antioxidative defenses, and changes in the major regulatory systems that serve to maintain the finely tuned balance of oxidative signaling vs. oxidative stress in lens cells. Age-related breakdown of these redox homeostasis systems in the lens leads to the onset of cataractogenesis. We propose eight candidate hallmarks that represent common denominators of aging and cataractogenesis in the mammalian lens: oxidative stress, altered cell signaling, loss of proteostasis, mitochondrial dysfunction, dysregulated ion homeostasis, cell senescence, genomic instability and intrinsic apoptotic cell death.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2021.108709},
	author = {Wishart, Tayler F L and Flokis, Mary and Shu, Daisy Y and Das, Shannon J and Lovicu, Frank J}
}
@article {416881,
	title = {Postoperative Hemorrhagic Occlusive Retinal Vasculitis: Expanding the Clinical Spectrum and Possible Association with Vancomycin.},
	journal = {Ophthalmology},
	volume = {122},
	number = {7},
	year = {2015},
	month = {2015 Jul},
	pages = {1438-51},
	abstract = {PURPOSE: To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN: Retrospective case series. SUBJECTS: Eleven eyes of 6 patients from 6 different institutions. METHODS: Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES: Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS: Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS: Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2015.03.016},
	author = {Witkin, Andre J and Shah, Anjali R and Engstrom, Robert E and Kron-Gray, Michelle M and Baumal, Caroline R and Johnson, Mark W and Witkin, Deborah I and Leung, John and Albini, Thomas A and Moshfeghi, Andrew A and Batlle, Ivan R and Sobrin, Lucia and Eliott, Dean}
}
@article {988046,
	title = {Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: Clinical Characteristics of 36 Eyes},
	journal = {Ophthalmology},
	volume = {124},
	number = {5},
	year = {2017},
	month = {2017 May},
	pages = {583-595},
	abstract = {
	PURPOSE: To expand understanding of presentation, diagnosis, and outcomes of hemorrhagic occlusive retinal vasculitis (HORV). DESIGN: Retrospective case series. PARTICIPANTS: Thirty-six eyes of 23 patients. METHODS: The American Society of Cataract and Refractive Surgery (ASCRS) and the American Society of Retina Specialists (ASRS) formed a joint task force to define clinical characteristics of HORV and to study its prevalence, cause, treatment, and outcomes. An online registry was established on both societies{\textquoteright} web sites. Surveys were e-mailed to members of both societies soliciting cases of suspected HORV. A literature search was performed to uncover additional cases. MAIN OUTCOME MEASURES: Historical data including intraoperative characteristics, images, treatment regimens, and visual and anatomic outcomes. RESULTS: Characteristic findings of HORV included unremarkable postoperative day 1 undilated examination, delayed-onset painless vision loss, mild anterior chamber and vitreous inflammation, sectoral retinal hemorrhages in areas of ischemia, and predilection for venules and peripheral involvement. Based on predetermined diagnostic criteria, 36 eyes of 23 patients were diagnosed with HORV. All eyes received intraocular vancomycin via intracameral bolus (33/36), via intravitreal injection (1/36), or through the irrigation bottle (2/36). Patients sought treatment with HORV 1 to 21 days after surgery or intravitreal injection. Visual results usually were poor: 22 of 36 eyes (61\%) had 20/200 or worse visual acuity and 8 of 36 eyes (22\%) had no light perception (NLP). Neovascular glaucoma developed in 20 of 36 eyes (56\%). Seven eyes received additional intravitreal vancomycin after surgery; 5 of these 7 eyes had NLP visual acuity at the most recent examination. Three eyes received intravitreal corticosteroids and had final visual acuities of 20/40, 20/70, and hand movements. CONCLUSIONS: Hemorrhagic occlusive retinal vasculitis is a rare, potentially devastating condition that can develop after cataract surgery or intraocular injection. All cases in this series were associated with intraocular vancomycin. Disease course and findings suggest that HORV is caused by a delayed hypersensitivity reaction to vancomycin. Early treatment with corticosteroids likely is beneficial. Subsequently, anti-vascular endothelial growth factor injections and panretinal photocoagulation are important to prevent neovascular glaucoma, a common complication. Avoidance of additional intravitreal vancomycin is recommended if HORV is suspected.

},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.11.042},
	author = {Witkin, Andre J and Chang, David F and Jumper, J Michael and Charles, Steve and Eliott, Dean and Hoffman, Richard S and Mamalis, Nick and Miller, Kevin M and Wykoff, Charles C}
}
@article {1337047,
	title = {Plasma gelsolin promotes re-epithelialization},
	journal = {Sci Rep},
	volume = {8},
	number = {1},
	year = {2018},
	pages = {13140},
	abstract = {Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-β dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-β dependent cell differentiation.},
	author = {Wittmann, J and Dieckow, J and Schr{\"o}der, H and Hampel, U and Garreis, F and Jacobi, C and Milczarek, A and Hsieh, KL and Pulli, B and Chen, JW and Hoogeboom, S and Br{\"a}uer, L and Paulsen, FP and Schob, S and Schicht, M}
}
@article {1549017,
	title = {Interventions for Indirect Traumatic Optic Neuropathy: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {128},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {928-937},
	abstract = {PURPOSE: To review the literature on the efficacy and safety of medical and surgical interventions for indirect traumatic optic neuropathy (TON), defined as injury to the nerve that occurs distal to the optic nerve head. METHODS: A literature search was conducted on October 22, 2019, and updated on April 8, 2020, in the PubMed database for English language original research that assessed the effect of various interventions for indirect TON. One hundred seventy-two articles were identified; 41 met the inclusion criteria outlined for assessment and were selected for full-text review and abstraction. On full-text review, a total of 32 studies met\&nbsp;all of the study criteria and were included in the analysis. RESULTS: No study met criteria for level I evidence. Seven studies (1 level II study and 6 level III studies) explored corticosteroid therapy that did not have uniformly better outcomes than observation. Twenty studies (3 level II studies and 17 level III studies) assessed optic canal decompression and the use of corticosteroids. Although visual improvement was noted after decompression, studies that directly compared surgery with medical therapy did not report uniformly improved outcomes after decompression. Four studies (1 level II study and 3 level III studies) evaluated the use of erythropoietin. Although initial studies demonstrated benefit, a direct comparison of its use with observation and corticosteroids failed to confirm the usefulness of this medication. One study (level II) documented visual improvement with levodopa plus carbidopa. Complication rates were variable with all of these interventions. Pharmacologic interventions generally were associated with few complications, whereas optical canal decompression carried risks of serious side effects, including hemorrhages and cerebrospinal fluid leakage. CONCLUSIONS: Despite reports of visual improvement with corticosteroids, optic canal decompression, and medical therapy for indirect TON, the weight of published evidence does not demonstrate a consistent benefit for any of these interventions. In summary, no consensus exists from studies published to date on a preferred treatment for TON. Treatment strategies should be customized for each individual patient. More definitive treatment trials will be needed to identify optimal treatment strategies for indirect TON.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.10.038},
	author = {Wladis, Edward J and Aakalu, Vinay K and Sobel, Rachel K and McCulley, Timothy J and Foster, Jill A and Tao, Jeremiah P and Freitag, Suzanne K and Yen, Michael T}
}
@article {837001,
	title = {Clinical and microbiologic features of dacryocystitis-related orbital cellulitis.},
	journal = {Orbit},
	volume = {35},
	number = {5},
	year = {2016},
	month = {2016 Oct},
	pages = {258-61},
	abstract = {Dacryocystitis-related orbital cellulitis is a relatively rare condition, and large case series of this clinical entity have been reported. This study was undertaken to identify a larger cohort of patients with this ailment, with the intent of defining its clinical and microbiologic features. Case logs from four institutions were reviewed to identify patients that suffered from dacryocystitis-related orbital cellulitis. A retrospective chart review was then performed to identify clinical features, management strategies, microbiologic features, and outcomes. A dedicated statistical software package was utilized to identify correlations between these variables. 13 patients (7 females, 6 males; mean age = 57.2 years, range = 7-89 years) were identified. One patient carried a diagnosis of immunosuppressive disease. All patients underwent emergent surgical drainage and received intravenous antibiotics. Primary acquired nasolacrimal duct obstruction was found to be the underlying etiology in nine cases (69.2\%), whereas four patients suffered from specific causes of their obstructions. An average of 1.07 organisms/patient (standard deviation = 0.49 organisms/patient) were recovered from microbiologic cultures, and Gram-positive bacteria represented the majority of cultured organisms. All patients experienced either stable or improved vision upon discharge. The relationships between a specific etiology and the possibility of vision loss or the number of organisms cultured, between the number of organisms cultured and vision loss, and immunosuppression and vision loss or the number of organisms cultured were all not statistically significant (p \&gt; 0.05). Dacryocystitis-related orbital cellulitis most commonly occurs in adult patients who do not carry immunosuppressive diagnoses and suffer from primary obstructions. Multiple microbiologic species may cause this problem, although Gram-positive organisms are most common. With appropriate management, stable or improved vision can be achieved.},
	issn = {1744-5108},
	doi = {10.1080/01676830.2016.1176214},
	author = {Wladis, Edward J and Shinder, Roman and Lefebvre, Daniel R and Sokol, Jason A and Boyce, Michelle}
}
@article {1435425,
	title = {Monocanalicular Stents in Eyelid Lacerations: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {126},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {1324-1329},
	abstract = {PURPOSE: To determine the efficacy and complication rates of monocanalicular stents in the setting of canalicular lacerations. METHODS: A literature search was performed in May 2018 in the PubMed database to identify all English-language reports of monocanalicular stenting to address canalicular lacerations. Studies that did not include at least 10 patients with at least 3 months of follow-up evaluation after surgery were excluded. Ninety-nine articles were identified, and 15 of these met criteria for data abstraction and were included in this assessment. The panel methodologist (V.K.A.) evaluated the quality of evidence and assigned a level-of-evidence rating to each of these studies. RESULTS: All 15 studies were rated as level III evidence. Anatomic and functional success rates after surgery ranged from 68\% to 100\% and 79\% to 100\%, respectively. Stents were generally well tolerated, although extrusion rates varied from 0\% to 29\%. CONCLUSIONS: Only level III evidence was available, and studies were not powered to detect differences between groups for rare complications or failure. Monocanalicular stents seem to be efficacious and well tolerated in the management of canalicular lacerations. Potential complications include extrusion (most commonly), tube displacement, granuloma, ectropion, slit punctum, fistula, and infection. Further comparative studies would help to identify the optimal time for device removal and to directly compare monocanalicular with bicanalicular stents.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2019.03.045},
	author = {Wladis, Edward J and Aakalu, Vinay K and Tao, Jeremiah P and Sobel, Rachel K and Freitag, Suzanne K and Foster, Jill A and Mawn, Louise A}
}
@article {1504057,
	title = {Intense Pulsed Light for Meibomian Gland Disease: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {127},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {1227-1233},
	abstract = {PURPOSE: To review the literature on the efficacy of intense pulsed light (IPL) on the eyelids in the management of meibomian gland disease (MGD) and meibomian gland-related ocular surface disease. METHODS: A literature search was last conducted on May 15, 2019, in the PubMed and Cochrane Library databases for English-language original research that assessed the effect of IPL on MGD in adult patients. Thirty-three articles were identified, and 12 studies were determined to be relevant to the criteria outlined for assessment. The panel methodologist (V.K.A.) assigned a level of evidence rating to each study; 4 studies were rated level II, and 8 studies were rated level III. Five studies had potential conflicts of interest and design limitations that affected interpretation of results. RESULTS: All studies documented improvement in clinically meaningful metrics, including tear breakup time (TBUT), corneal staining and eyelid margin measurements, meibum quality, meibomian gland expressability, ocular surface disease index (OSDI), and standard patient evaluation of eye dryness (SPEED) questionnaire scores. Side effects were relatively uncommon but included discomfort, cutaneous erythema, blistering, eyelash loss, and floaters; these were uniformly self-limited. CONCLUSIONS: Although methodological limitations and potential conflicts of interest in some studies raised concern, the existing body of literature demonstrates improvements in the signs and symptoms of MGD after IPL therapy.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.03.009},
	author = {Wladis, Edward J and Aakalu, Vinay K and Foster, Jill A and Freitag, Suzanne K and Sobel, Rachel K and Tao, Jeremiah P and Yen, Michael T}
}
@article {1817241,
	title = {Preloaded DMEK With Endothelium Outward: A Multicenter Clinical Study Using DMEK Rapid Device},
	journal = {Cornea},
	volume = {43},
	number = {1},
	year = {2024},
	month = {2024 Jan 01},
	pages = {38-44},
	abstract = {PURPOSE: The objective of this study is to validate Descemet membrane endothelial keratoplasty (DMEK) Rapid device for preloading DMEK grafts with endothelium outward.

METHODS: In this multicenter retrospective clinical study, DMEK tissues (n = 27) were peeled and preloaded (8.25 mm) in a DMEK Rapid device. The device was loaded in a container prefilled with the storage solution and shipped from a single center in Italy to 4 different centers located in Italy and the United Kingdom. Preloaded tissues were delivered by injecting the graft in the anterior chamber. Patients were monitored at days 1 and 15 and at months 1, 3, and 6, as well as at the last follow-up (9-12 months) postoperatively. Main outcome measures included rebubbling rate and graft failure, corrected distance visual acuity, endothelial cell loss (ECL), and central corneal thickness at all time points. A one-way analysis of variance test comparing day 1 with all later time points was followed with significance at P \&lt; 0.05.

RESULTS: The average recorded surgical time was 6 to 25 minutes with no immediate surgical complications. Rebubbling was observed in 7 of 26 cases with one graft failure within 15 days postoperatively. The mean corrected distance visual acuity at day 1 was 0.64 {\textpm} 0.49 logMAR, which improved to 0.18 {\textpm} 0.43 logMAR at the last follow-up. Endothelial cell density values showed a significant decrease at the last follow-up (1827 {\textpm} 565 cells/mm 2 ) ( P \&lt; 0.001) compared with the preoperative value (2503 {\textpm} 128 cells/mm 2 ), with an average endothelial cell loss of 27\%. Central corneal thickness significantly dropped from 694 {\textpm} 157 μm at day 1 to 502 {\textpm} 42 μm at the last follow-up ( P \&lt; 0.001).

CONCLUSIONS: DMEK Rapid device is quick, easy, and efficient for preloading and shipping DMEK grafts internationally in endothelium-outward orientation.},
	keywords = {Cell Count, Corneal Endothelial Cell Loss, Descemet Membrane, Descemet Stripping Endothelial Keratoplasty, Endothelium, Corneal, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Retrospective Studies, Visual Acuity},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000003274},
	author = {Wojcik, Gabriela and Parekh, Mohit and Romano, Vito and Ruzza, Alessandro and Scorcia, Vincenzo and Viola, Pietro and Leon, Pia and Franch, Antonella and Gadhvi, Kunal A and Ponzin, Diego and Ferrari, Stefano}
}
@article {1814441,
	title = {Liquid Biopsy Proteomics in Ophthalmology},
	journal = {J Proteome Res},
	volume = {23},
	number = {2},
	year = {2024},
	month = {2024 Feb 02},
	pages = {511-522},
	abstract = {Minimally invasive liquid biopsies from the eye capture locally enriched fluids that contain thousands of proteins from highly specialized ocular cell types, presenting a promising alternative to solid tissue biopsies. The advantages of liquid biopsies include sampling the eye without causing irreversible functional damage, potentially better reflecting tissue heterogeneity, collecting samples in an outpatient setting, monitoring therapeutic response with sequential sampling, and even allowing examination of disease mechanisms at the cell level in living humans, an approach that we refer to as TEMPO (Tracing Expression of Multiple Protein Origins). Liquid biopsy proteomics has the potential to transform molecular diagnostics and prognostics and to assess disease mechanisms and personalized therapeutic strategies in individual patients. This review addresses opportunities, challenges, and future directions of high-resolution liquid biopsy proteomics in ophthalmology, with particular emphasis on the large-scale collection of high-quality samples, cutting edge proteomics technology, and artificial intelligence-supported data analysis.},
	keywords = {Artificial Intelligence, Biopsy, Humans, Liquid Biopsy, Ophthalmology, Proteins, Proteomics},
	issn = {1535-3907},
	doi = {10.1021/acs.jproteome.3c00756},
	author = {Wolf, Julian and Franco, Joel A and Yip, Rui and Dabaja, Mohamed Ziad and Velez, Gabriel and Liu, Fei and Bassuk, Alexander G and Mruthyunjaya, Prithvi and Dufour, Antoine and Mahajan, Vinit B}
}
@article {1664963,
	title = {Spatial and temporal massive memory in humans},
	journal = {Curr Biol},
	volume = {33},
	number = {2},
	year = {2023},
	month = {2023 Jan 23},
	pages = {405-410.e4},
	abstract = {It is well known that humans have a massive memory for pictures and scenes.1,2,3,4 They show an ability to encode thousands of images with only a few seconds of exposure to each. In addition to this massive memory for "what" observers have seen, three experiments reported here show that observers have a "spatial massive memory" (SMM) for "where" stimuli have been seen and a "temporal massive memory" (TMM) for "when" stimuli have been seen. The positions in time and space for at least dozens of items can be reported with good, if not perfect accuracy. Previous work has suggested that there might be good memory for stimulus location,5,6 but there do not seem to have been concerted efforts to measure the extent of this memory. Moreover, in our method, observers are recalling where items were located and not merely recognizing the correct location. This is interesting because massive memory is sometimes thought to be limited to recognition tasks based on sense of familiarity.},
	keywords = {Cognition, Humans, Mental Recall, Recognition, Psychology, Spatial Memory},
	issn = {1879-0445},
	doi = {10.1016/j.cub.2022.12.040},
	author = {Wolfe, Jeremy M and Wick, Farahnaz A and Maruti Mishra and DeGutis, Joseph and Lyu, Wanyi}
}
@article {1483601,
	title = {Forty years after feature integration theory: An introduction to the special issue in honor of the contributions of Anne Treisman},
	journal = {Atten Percept Psychophys},
	year = {2020},
	month = {2020 Jan 16},
	issn = {1943-393X},
	doi = {10.3758/s13414-019-01966-3},
	author = {Wolfe, Jeremy M}
}
@article {635021,
	title = {Hybrid foraging search: Searching for multiple instances of multiple types of target.},
	journal = {Vision Res},
	volume = {119},
	year = {2016},
	month = {2016 Feb},
	pages = {50-9},
	abstract = {This paper introduces the "hybrid foraging" paradigm. In typical visual search tasks, observers search for one instance of one target among distractors. In hybrid search, observers search through visual displays for one instance of any of several types of target held in memory. In foraging search, observers collect multiple instances of a single target type from visual displays. Combining these paradigms, in hybrid foraging tasks observers search visual displays for multiple instances of any of several types of target (as might be the case in searching the kitchen for dinner ingredients or an X-ray for different pathologies). In the present experiment, observers held 8-64 target objects in memory. They viewed displays of 60-105 randomly moving photographs of objects and used the computer mouse to collect multiple targets before choosing to move to the next display. Rather than selecting at random among available targets, observers tended to collect items in runs of one target type. Reaction time (RT) data indicate searching again for the same item is more efficient than searching for any other targets, held in memory. Observers were trying to maximize collection rate. As a result, and consistent with optimal foraging theory, they tended to leave 25-33\% of targets uncollected when moving to the next screen/patch. The pattern of RTs shows that while observers were collecting a target item, they had already begun searching memory and the visual display for additional targets, making the hybrid foraging task a useful way to investigate the interaction of visual and memory search.},
	issn = {1878-5646},
	doi = {10.1016/j.visres.2015.12.006},
	author = {Wolfe, Jeremy M and Aizenman, Avigael M and Boettcher, Sage E P and Cain, Matthew S}
}
@article {1580475,
	title = {Guided Search 6.0: An updated model of visual search},
	journal = {Psychon Bull Rev},
	volume = {28},
	number = {4},
	year = {2021},
	month = {2021 Aug},
	pages = {1060-1092},
	abstract = {This paper describes Guided Search 6.0 (GS6), a revised model of visual search. When we encounter a scene, we can see something everywhere. However, we cannot recognize more than a few items at a time. Attention is used to select items so that their features can be "bound" into recognizable objects. Attention is "guided" so that items can be processed in an intelligent order. In GS6, this guidance comes from five sources of preattentive information: (1) top-down and (2) bottom-up feature guidance, (3) prior history (e.g., priming), (4) reward, and (5) scene syntax and semantics. These sources are combined into a spatial "priority map," a dynamic attentional landscape that evolves over the course of search. Selective attention is guided to the most active location in the priority map approximately 20 times per second. Guidance will not be uniform across the visual field. It will favor items near the point of fixation. Three types of functional visual field (FVFs) describe the nature of these foveal biases. There is a resolution FVF, an FVF governing exploratory eye movements, and an FVF governing covert deployments of attention. To be identified as targets or rejected as distractors, items must be compared to target templates held in memory. The binding and recognition of an attended object is modeled as a diffusion process taking \&gt; 150 ms/item. Since selection occurs more frequently than that, it follows that multiple items are undergoing recognition at the same time, though asynchronously, making GS6 a hybrid of serial and parallel processes. In GS6, if a target is not found, search terminates when an accumulating quitting signal reaches a threshold. Setting of that threshold is adaptive, allowing feedback about performance to shape subsequent searches. Simulation shows that the combination of asynchronous diffusion and a quitting signal can produce the basic patterns of response time and error data from a range of search experiments.},
	issn = {1531-5320},
	doi = {10.3758/s13423-020-01859-9},
	author = {Wolfe, Jeremy M}
}
@article {1360125,
	title = {What is a preattentive feature?},
	journal = {Curr Opin Psychol},
	volume = {29},
	year = {2018},
	month = {2018 Nov 13},
	pages = {19-26},
	abstract = {The concept of a preattentive feature has been central to vision and attention research for about half a century. A preattentive feature is a feature that guides attention in visual search and that cannot be decomposed into simpler features. While that definition seems straightforward, there is no simple diagnostic test that infallibly identifies a preattentive feature. This paper briefly reviews the criteria that have been proposed and illustrates some of the difficulties of definition.},
	issn = {2352-2518},
	doi = {10.1016/j.copsyc.2018.11.005},
	author = {Wolfe, Jeremy M and Utochkin, Igor S}
}
@article {1504058,
	title = {Visual Search: How Do We Find What We Are Looking For?},
	journal = {Annu Rev Vis Sci},
	volume = {6},
	year = {2020},
	month = {2020 Sep 15},
	pages = {539-562},
	abstract = {In visual search tasks, observers look for targets among distractors. In the lab, this often takes the form of multiple searches for a simple shape that may or may not be present among other items scattered at random on a computer screen (e.g., Find a red T among other letters that are either black or red.). In the real world, observers may search for multiple classes of target in complex scenes that occur only once (e.g., As I emerge from the subway, can I find lunch, my friend, and a street sign in the scene before me?). This article reviews work on how search is guided intelligently. I ask how serial and parallel processes collaborate in visual search, describe the distinction between search templates in working memory and target templates in long-term memory, and consider how searches are terminated.},
	issn = {2374-4650},
	doi = {10.1146/annurev-vision-091718-015048},
	author = {Wolfe, Jeremy M}
}
@article {742331,
	title = {HOW DO RADIOLOGISTS USE THE HUMAN SEARCH ENGINE?},
	journal = {Radiat Prot Dosimetry},
	volume = {169},
	number = {1-4},
	year = {2016},
	month = {2016 Jun},
	pages = {24-31},
	abstract = {Radiologists perform many {\textquoteright}visual search tasks{\textquoteright} in which they look for one or more instances of one or more types of target item in a medical image (e.g. cancer screening). To understand and improve how radiologists do such tasks, it must be understood how the human {\textquoteright}search engine{\textquoteright} works. This article briefly reviews some of the relevant work into this aspect of medical image perception. Questions include how attention and the eyes are guided in radiologic search? How is global (image-wide) information used in search? How might properties of human vision and human cognition lead to errors in radiologic search?},
	issn = {1742-3406},
	doi = {10.1093/rpd/ncv501},
	author = {Wolfe, Jeremy M and Evans, Karla K and Drew, Trafton and Aizenman, Avigael and Josephs, Emilie}
}
@article {1417583,
	title = {Guidance and selection history in hybrid foraging visual search},
	journal = {Atten Percept Psychophys},
	volume = {81},
	number = {3},
	year = {2019},
	month = {2019 Apr},
	pages = {637-653},
	abstract = {In Hybrid Foraging tasks, observers search for multiple instances of several types of target. Collecting all the dirty laundry and kitchenware out of a child{\textquoteright}s room would be a real-world example. How are such foraging episodes structured? A series of four experiments shows that selection of one item from the display makes it more likely that the next item will be of the same type. This pattern holds if the targets are defined by basic features like color and shape but not if they are defined by their identity (e.g., the letters p \&amp; d). Additionally, switching between target types during search is expensive in time, with longer response times between successive selections if the target type changes than if they are the same. Finally, the decision to leave a screen/patch for the next screen in these foraging tasks is imperfectly consistent with the predictions of optimal foraging theory. The results of these hybrid foraging studies cast new light on the ways in which prior selection history guides subsequent visual search in general.},
	issn = {1943-393X},
	doi = {10.3758/s13414-018-01649-5},
	author = {Wolfe, Jeremy M and Cain, Matthew S and Aizenman, Avigael M}
}
@article {603886,
	title = {You look familiar, but I don{\textquoteright}t care: Lure rejection in hybrid visual and memory search is not based on familiarity.},
	journal = {J Exp Psychol Hum Percept Perform},
	volume = {41},
	number = {6},
	year = {2015},
	month = {2015 Dec},
	pages = {1576-87},
	abstract = {In "hybrid" search tasks, observers hold multiple possible targets in memory while searching for those targets among distractor items in visual displays. Wolfe (2012) found that, if the target set is held constant over a block of trials, reaction times (RTs) in such tasks were a linear function of the number of items in the visual display and a linear function of the log of the number of items held in memory. However, in such tasks, the targets can become far more familiar than the distractors. Does this "familiarity"- operationalized here as the frequency and recency with which an item has appeared-influence performance in hybrid tasks In Experiment 1, we compared searches where distractors appeared with the same frequency as the targets to searches where all distractors were novel. Distractor familiarity did not have any reliable effect on search. In Experiment 2, most distractors were novel but some critical distractors were as common as the targets while others were 4{\texttimes} more common. Familiar distractors did not produce false alarm errors, though they did slightly increase RTs. In Experiment 3, observers successfully searched for the new, unfamiliar item among distractors that, in many cases, had been seen only once before. We conclude that when the memory set is held constant for many trials, item familiarity alone does not cause observers to mistakenly confuse target with distractors. (PsycINFO Database Record},
	issn = {1939-1277},
	doi = {10.1037/xhp0000096},
	author = {Wolfe, Jeremy M and Boettcher, Sage E P and Josephs, Emilie L and Cunningham, Corbin A and Drew, Trafton}
}
@article {1504066,
	title = {Major issues in the study of visual search: Part 2 of "40 Years of Feature Integration: Special Issue in Memory of Anne Treisman"},
	journal = {Atten Percept Psychophys},
	year = {2020},
	month = {2020 Apr 10},
	issn = {1943-393X},
	doi = {10.3758/s13414-020-02022-1},
	author = {Wolfe, Jeremy M}
}
@article {1195231,
	title = {Visual Attention: Size Matters},
	journal = {Curr Biol},
	volume = {27},
	number = {18},
	year = {2017},
	month = {2017 Sep 25},
	pages = {R1002-R1003},
	abstract = {When searching real-world scenes, human attention is guided by knowledge of the plausible size of target object (if an object is six feet tall, it isn{\textquoteright}t your cat). Computer algorithms typically do not do this, but perhaps they should.},
	issn = {1879-0445},
	doi = {10.1016/j.cub.2017.07.057},
	author = {Wolfe, Jeremy M}
}
@article {1619413,
	title = {National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report},
	journal = {Transplant Cell Ther},
	volume = {27},
	number = {10},
	year = {2021},
	month = {2021 10},
	pages = {817-835},
	abstract = {Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.},
	keywords = {Chronic Disease, Consensus, Graft vs Host Disease, Humans, Incidence, National Institutes of Health (U.S.), Quality of Life, United States},
	issn = {2666-6367},
	doi = {10.1016/j.jtct.2021.06.001},
	author = {Wolff, Daniel and Radojcic, Vedran and Lafyatis, Robert and Cinar, Resat and Rosenstein, Rachel K and Cowen, Edward W and Cheng, Guang-Shing and Sheshadri, Ajay and Bergeron, Anne and Williams, Kirsten M and Todd, Jamie L and Teshima, Takanori and Cuvelier, Geoffrey D E and Holler, Ernst and McCurdy, Shannon R and Jenq, Robert R and Hanash, Alan M and Jacobsohn, David and Santomasso, Bianca D and Jain, Sandeep and Ogawa, Yoko and Steven, Philipp and Luo, Zhonghui Katie and Dietrich-Ntoukas, Tina and Saban, Daniel and Bilic, Ervina and Penack, Olaf and Griffith, Linda M and Cowden, Meredith and Martin, Paul J and Greinix, Hildegard T and Sarantopoulos, Stefanie and Socie, Gerard and Blazar, Bruce R and Pidala, Joseph and Kitko, Carrie L and Couriel, Daniel R and Cutler, Corey and Schultz, Kirk R and Pavletic, Steven Z and Lee, Stephanie J and Paczesny, Sophie}
}
@article {988051,
	title = {Chronic orbital and calvarial fungal infection with Apophysomyces variabilis in an immunocompetent patient.},
	journal = {Surv Ophthalmol},
	volume = {62},
	number = {1},
	year = {2017},
	pages = {70-82},
	abstract = {Apophysomyces is a rare fungal organism causing rhino-orbito-cerebral mycotic infections with high morbidity and mortality, typically in immunocompetent individuals. Several cases of Apophysomyces elegans orbital disease have been reported. Herein, we report a case of Apophysomyces variabilis infection involving the orbit, sinuses, and calvarium in an immunocompetent 74-year-old woman, with a review of the literature. Unlike prior cases of A. elegans classic rhino-orbito-cerebral infection, our case included diffuse calvarial lytic lesions and overlying soft tissue nodules, but without parenchymal intracranial involvement. There was radiographic and clinical evidence of infarction of the orbital\&nbsp;contents and cavernous sinus thrombosis. Anastomoses between the superior orbital (ophthalmic) vein and diploic veins of the calvarium are believed to be primarily responsible for the unusual mode of spread on the extradural surface of the brain. Although the patient stabilized without definitive surgical intervention, her disease slowly and intermittently progressed for over a year after presentation, requiring multiple courses of antifungal treatment.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2016.05.006},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Stagner, Anna M and Cunnane, Mary E and Piantadosi, Anne L and Basgoz, Nesli and Lefebvre, Daniel}
}
@article {1522721,
	title = {High Expression of Programmed Death Ligand 1 and Programmed Death Ligand 2 in Ophthalmic Sebaceous Carcinoma: The Case for a Clinical Trial of Checkpoint Inhibitors},
	journal = {Am J Ophthalmol},
	volume = {220},
	year = {2020},
	month = {2020 12},
	pages = {128-139},
	abstract = {PURPOSE: To evaluate the expression of programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) in ocular adnexal sebaceous carcinoma (OASC), and to appraise these findings within the context of recent comparable studies. DESIGNS: Retrospective case series. METHODS: Twenty cases of primary OASC were immunostained for PD-L1, PD-L2 and CD8. PD-L1 and PD-L2 expression were graded with both the combined positive score (CPS) and the tumor proportion score (TPS). Both raw CPS and TPS were reported, as well as positivity with TPS and CPS >=1. CD8 expression was graded on a 0-3 scale. Charts were reviewed for clinical correlations. The results of the current study were compared with results of similar recent investigations. RESULTS: For the 20 cases, mean expression of PD-L1 with CPS was 29.7 (range 0-101.5) and with TPS was 12.2 (range 0-95.8); mean expression of PD-L2 with CPS was 7.9 (range 0-37.3) and with TPS was 1.9 (range 0-12.9). PD-L1 CPS >=1 was detected in 95\% of OASC, while PD-L1 TPS >=1 was found in 75\%. PD-L2 CPS >=1 was present in 60\%, while only 20\% had PD-L2 TPS >=1. Immune cells appeared to contribute to a substantial proportion of PD-L1 and PD-L2 positivity, and a conspicuous CD8-positive T-lymphocytic infiltrate was present in most tumors. Significant correlations were identified between tissue expression of PD-L1, PD-L2, and CD8. Tissues with greater levels of PD-L1 tended to express higher levels of PD-L2 and CD8. The degree of PD-L1 and PD-L2 expression was also associated with the area in millimeters squared of the immunostained tumor, suggesting that tumor sampling may influence interpretation of PD-L1 and PD-L2 expression in ocular adnexal tumors. CONCLUSIONS: The current and preceding studies confirm that PD-L1 and PD-L2 are expressed in a high percentage of OASCs. These results support the premise that checkpoint inhibitor drugs hold considerable therapeutic promise for patients with OASC and stimulate the institution of clinical trials.},
	keywords = {Adenocarcinoma, Sebaceous, Adolescent, Adult, Aged, Aged, 80 and over, B7-H1 Antigen, Biomarkers, Tumor, Child, Child, Preschool, Eye Neoplasms, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Programmed Cell Death 1 Ligand 2 Protein, Retrospective Studies, RNA, Neoplasm, Sebaceous Gland Neoplasms, Young Adult},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.07.031},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Afrogheh, Amir H and Pai, Sara I and Faquin, William C}
}
@article {1732641,
	title = {Case 21-2023: A 61-Year-Old Man with Eyelid Swelling},
	journal = {N Engl J Med},
	volume = {389},
	number = {2},
	year = {2023},
	month = {2023 Jul 13},
	pages = {166-175},
	keywords = {Angioedema, Edema, Eye Diseases, Eyelid Diseases, Eyelids, Humans, Male, Middle Aged},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc2300904},
	author = {Wolkow, Natalie and Romo, Laura V and Edwards, Camille V and Stagner, Anna M}
}
@article {1511497,
	title = {Seborrheic Keratosis Concealing a Basal Cell Carcinoma},
	journal = {Ophthalmic Plast Reconstr Surg},
	year = {2020},
	month = {2020 May 19},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001706},
	author = {Wolkow, Natalie and Yoon, Michael K}
}
@article {1430544,
	title = {Balloon Cell Nevus in a 13-Year-Old Girl: Clinical and Histopathologic Features},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {5},
	year = {2019},
	month = {2019 Sep/Oct},
	pages = {e125},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001340},
	author = {Wolkow, Natalie and Freitag, Suzanne K}
}
@article {1295885,
	title = {Gelatin-Based Hemostatic Agents: Histopathologic Differences},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2018},
	month = {2018 Jan 12},
	abstract = {PURPOSE: To delineate the histopathologic appearance of gelatin-based hemostatic agents, Surgiflo, Gelfoam, and Floseal, which are used by ophthalmic plastic surgeons, and which may incidentally be found as foreign materials in histopathologic tissue samples. METHODS: Histopathologic analysis was performed with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, and elastin staining on tissue samples in which gelatin-based agents were found. To better characterize these materials, similar analyses were performed on in vitro samples of commonly used gelatin-based hemostatic agents. RESULTS: Surgiflo and Gelfoam are composed of small stellate pieces of gelatin with a smooth, homogeneous quality. In tissues, they are faintly positive with periodic acid-Schiff staining, amphophilic with Masson trichrome staining, and ink-black with elastin staining. Floseal has a distinctly different morphology of large rectangular sheets, yet almost identical in vitro staining properties. DISCUSSION: While the morphology of the gelatin-based hemostatic agents is consistent under various conditions, the staining properties of these materials differ based on whether they have been in contact with human tissue. CONCLUSIONS: Gelatin-derived hemostatic agents are best identified based on their morphologic characteristics. Elastin staining highlights these materials prominently within tissue samples and may be helpful in distinguishing them from other foreign materials.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001048},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Yoon, Michael K}
}
@article {1460373,
	title = {Corneal Neurotization: Review of a New Surgical Approach and Its Developments},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Aug 01},
	pages = {1-15},
	abstract = {Corneal neurotization is an innovative surgical approach for restoring corneal sensation, whereby the sensory functions of a normal donor nerve are rerouted to an anesthetic cornea. Many variations upon this basic surgical principal have been introduced and have proven successful in ameliorating corneal sensation in patients. It is unclear whether one surgical approach is superior to another, as each has advantages and disadvantages. Surgical approaches differ in the donor nerve selected and in whether a nerve graft is required. Surgical techniques have varied in the location, number and extent of incisions, methods of nerve coaptation, the number of surgeons required, the equipment and materials utilized and the duration of the procedure. The current review provides an overview of developments in this nascent field. A review of all peer-reviewed publications on corneal neurotization was performed. The various approaches to corneal neurotization are compared and discussed. The least morbid, simplest, most expedient and successful surgical approaches will ultimately become the most utilized.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1648692},
	author = {Wolkow, Natalie and Habib, Larissa A and Yoon, Michael K and Freitag, Suzanne K}
}
@article {1304392,
	title = {Dermalive Facial Filler Granulomas Masquerading as Neurofibromas},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {3},
	year = {2018},
	month = {2018 May/Jun},
	pages = {e99-e103},
	abstract = {A 56-year-old woman presented with periocular nodules that were clinically suspected to be neurofibromas. Histopathologic examination of excised nodules revealed a pronounced granulomatous reaction to a foreign material that was composed of glossy polygonal palely eosinophilic fragments. These fragments were outlined in red with Masson trichrome, stained gray with the elastic stain, and were uniformly red with Gomori methenamine silver staining. The histopathologic appearance was consistent with a granulomatous reaction to Dermalive facial filler. Postoperatively the patient admitted that she had filler injections many years earlier in another country, and that nodules appeared 1 year after injection. Treatment with steroids, intralesional immunosuppressive agents and surgery had been previously attempted to eradicate the nodules. The literature pertaining to granulomatous reactions to Dermalive and related hybrid facial fillers is reviewed and treatment options are discussed. This report is the first to illustrate the unique histopathologic staining characteristics of Dermalive, which may be useful to ophthalmic pathologists in identifying this uncommon foreign material.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001100},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Yoon, Michael K}
}
@article {1323947,
	title = {Long-term Outcomes of Globe-Preserving Surgery With Proton Beam Radiation for Adenoid Cystic Carcinoma of the Lacrimal Gland},
	journal = {Am J Ophthalmol},
	volume = {195},
	year = {2018},
	month = {2018 Nov},
	pages = {43-62},
	abstract = {PURPOSE: To describe outcomes of globe-preserving surgery combined with high-dose proton beam radiation (PBR) in treating primary adenoid cystic carcinoma (ACC) of the lacrimal gland. DESIGN: Retrospective case series. METHODS: Twenty-nine patients with primary ACC of the lacrimal gland were identified in the records of a single institution between 1990 and 2017. Patients with nonorbital primary tumor origins or with inadequate follow-ups were excluded. Eighteen patients met inclusion criteria. Clinical data, imaging studies, histopathology, treatment modality, local recurrences, visual outcomes, metastases, and survivals were assessed. Disease-free survivals for the current patients were measured and compared to those of other studies. RESULTS: The eighteen patients (14 female, 4 male) were followed for a median of 12.9 years (range 0.6-22.3 years) after treatment completion. Their median age was 40 years. Four were children (median age 12 years). All were treated with globe-preserving tumor resection and radiation (median dose of 72 cobalt gray equivalents). Three adult patients died of metastatic disease (median of 4.2 years after treatment). Four had local recurrences. Useful vision (20/40 or better) was retained for a median 3 years (range 1-12.9 years). Radiation morbidity included brain injury, retinopathy, optic neuropathy, keratopathy, and cataract. Overall and disease-free survivals were significantly better compared to historical treatments, but did not differ statistically from other modern approaches. CONCLUSIONS: Globe-preserving surgery with PBR, although imperfect, has a favorable long-term survival compared to other modern modalities, and offers a variable period of useful vision.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.07.024},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Lee, Hang and Sutula, Francis C}
}
@article {1522735,
	title = {LONG-TERM OBSERVATION OF MULTIFOCAL METASTATIC INTRAOCULAR CARCINOID WITH ACQUIRED IRIS HETEROCHROMIA},
	journal = {Retin Cases Brief Rep},
	volume = {14},
	number = {3},
	year = {2020},
	month = {2020 Summer},
	pages = {265-267},
	abstract = {BACKGROUND/PURPOSE: To report a unique case of a pulmonary carcinoid tumor unilaterally metastatic to the iris and ciliary body and bilaterally to the choroid that was conservatively followed. METHODS: A 46-year-old woman presented with bilateral choroidal lesions and a left iris tumor. Ultrasound biomicroscopy disclosed a ciliary body component. A diagnosis of metastatic carcinoid tumor was made based on the clinical features. Rather than an excision, photodynamic therapy, or radiation treatment, as has been reported in all previous cases of carcinoid tumor metastatic to the iris, the patient was observed. RESULTS: Excellent vision was maintained for 8 years. The iris tumor gradually enlarged, but the choroidal lesions remained unchanged. The iris with the carcinoid tumor gradually acquired a brown pigmentation; this is the first reported case of acquired iris heterochromia in the setting of carcinoid tumor. CONCLUSION: We conclude, in cases of metastatic carcinoid in which visual acuity is excellent and the patient is asymptomatic, that observation of the ocular lesions is an acceptable course of action. The iris heterochromia is believed to have been caused by secretory factors produced by the tumor.},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000690},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Gragoudas, Evangelos S}
}
@article {1233376,
	title = {A 70-Year-Old Man With Pain and a Creamy Elevated Lesion After Transscleral Cyclophotocoagulation},
	journal = {JAMA Ophthalmol},
	volume = {136},
	number = {2},
	year = {2018},
	month = {2018 Feb 01},
	pages = {209-210},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2017.3067},
	author = {Wolkow, Natalie and Papaliodis, George N and Turalba, Angela V}
}
@article {1483593,
	title = {PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {36},
	number = {5},
	year = {2020},
	month = {2020 Sep/Oct},
	pages = {444-450},
	abstract = {PURPOSE: To determine if there is a biologic rationale for using checkpoint inhibitor drugs targeting programmed cell death ligand 1 (PD-L1) and PD-L2 in the treatment of adenoid cystic carcinoma of the orbit. METHODS: Twenty-three cases of adenoid cystic carcinoma involving the orbit (13 primary lacrimal gland, 5 secondarily extending into the orbit, and 5 unspecified) were examined histopathologically. Immunohistochemistry for PD-L1, PD-L2, and CD8 was performed. Charts were reviewed for clinical correlations. RESULTS: Expression of PD-L1 and of PD-L2 was overall low in adenoid cystic carcinoma (mean expression 1.4 {\textpm} 0.9 of 5 for PD-L1, mean 0.83 {\textpm} 1.1 of 5 for PD-L2), and tumor-infiltrating CD8-positive T-lymphocytes were sparse (mean 1.1 {\textpm} 0.51 of 3). Only 13 of the 23 (57\%) cases expressed PD-L1 as a combined positive score >=1 of cells. No associations were found between expression levels of these markers and patient sex, tumor site of origin, Tumor, Node, Metastasis stage, or patient outcome. A significant association was observed between stromal PD-L1 expression and tumor histopathologic subtype (p = 0.05), and between tumor PD-L1 expression and prior exposure to radiation (p = 0.03). CONCLUSIONS: Checkpoint inhibitor drugs may have limited impact in the treatment and clinical course of orbital adenoid cystic carcinoma based on the low frequency of CD8 infiltrate and low expression of PD-L1 and PD-L2. Pretreatment with radiation, however, may improve tumor response to checkpoint inhibitor drugs.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001585},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Afrogheh, Amir H and Kidd, Martin and Eagle, Ralph C and Pai, Sara I and Faquin, William C}
}
@article {1059851,
	title = {A 64-Year-Old Man With Swollen, Blistered Eyelids},
	journal = {JAMA Ophthalmol},
	volume = {135},
	number = {6},
	year = {2017},
	month = {2017 Jun 01},
	pages = {669-670},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2016.5410},
	author = {Wolkow, Natalie and Yaremchuk, Michael J and Freitag, Suzanne K}
}
@article {1295883,
	title = {Mild Complications or Unusual Persistence of Porcine Collagen and Hyaluronic Acid Gel Following Periocular Filler Injections},
	journal = {Ophthal Plast Reconstr Surg},
	year = {2018},
	month = {2018 Jan 09},
	abstract = {The purpose of this study was to describe the histopathologic appearance of dermal eyelid fillers that were unexpectedly encountered in ophthalmic plastic surgery samples from patients with mild eyelid disfigurements, and to review eyelid cases with complications that had previously been described in the literature. A retrospective histopathologic study with Alcian blue, elastic, and Masson trichrome stains of 2 cases that were submitted to the Ocular Pathology Department was conducted, and a critical review of previously published cases of the histopathologic characteristics of dermal filler material in the periocular region was also conducted. Two periocular tissue samples were found to contain dermal filler material. In one case, porcine collagen appeared as amorphous or indistinctly microfibrillar aggregates that stained light blue with the Masson trichrome method. In the other case, hyaluronic acid gel appeared as vivid blue amorphous pools of material in extracellular locules after staining with the Alcian blue method. An inflammatory response was not observed in either case. Patients who undergo facial filler procedures may, at a later time, require a surgical excisional procedure from which a specimen is generated. Previously injected dermal filler that the patient neglected to mention may be present in the pathologic sample, potentially perplexing the unsuspecting pathologist. Both ophthalmic plastic surgeons and ocular pathologists should be aware of the histopathologic features of dermal fillers. It is helpful if a surgeon who submits a specimen to the pathology service makes note of any known prior use of facial filler material or is alert to its possible presence when unfamiliar foreign material is discovered in the dermis of the eyelids.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001029},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Dryja, Thaddeus P and Lefebvre, Daniel R}
}
@article {1287956,
	title = {Intratarsal Keratinous Eyelid Cysts in Gorlin Syndrome: A Review and Reappraisal},
	journal = {Surv Ophthalmol},
	year = {2017},
	month = {2017 Dec 26},
	abstract = {A 38-year-old woman presented with multiple bilateral recurrent eyelid cysts. Her medical history was notable for Gorlin (nevoid basal cell carcinoma) syndrome. Histopathologic and immunohistochemical examinations revealed that the lesions were intratarsal keratinous cysts. They were similar in appearance to sporadic intratarsal keratinous cysts and closely resembled odontogenic keratocysts of the jaw. Eyelid cysts occur in up to 40 percent of patients with Gorlin syndrome; however, their description has been cursory and for the most part, outside of the ophthalmic literature. Although ophthalmologists are familiar with the periocular basal cell carcinomas that occur in patients with Gorlin syndrome, up to 10 percent of patients never develop a basal cell carcinoma, but may manifest other ophthalmic findings. Awareness of these other features may contribute to the earlier diagnosis of the syndrome. We discuss the clinical and histopathologic features of intratarsal keratinous cysts in Gorlin syndrome, comparing them to sporadic intratarsal keratinous cysts, other eyelid cysts, and jaw cysts that also characterize this syndrome. We briefly review the ocular and systemic manifestations of Gorlin syndrome and recent genetic and therapeutic developments so that the eyelid cysts may be appreciated within the appropriate context of Gorlin syndrome as a whole.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2017.12.007},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Yoon, Michael K}
}
@article {1323948,
	title = {Ophthalmic Plastic Surgery in Patients 100 Years and Older},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {1},
	year = {2019},
	month = {2019 Jan/Feb},
	pages = {71-76},
	abstract = {PURPOSE: The centenarian population is growing and ophthalmic plastic surgeons are providing care to an increasing number of elderly patients. Outcomes of centenarians have not been previously studied in the ophthalmic plastic surgery literature. The goal of the current review was to examine the baseline characteristics, surgical problems, and outcomes of this select group of patients. METHODS: A retrospective chart review was performed. Patients who underwent ophthalmic plastic surgery at age 100 or older between January 2000 and June 2016 by a member of the New England Oculoplastics Society were included in the study. RESULTS: Fifteen patients met inclusion criteria. The majority (66\%) were female. More than half (60\%) presented with a surgical problem of an urgent nature. Most disorders involved the lacrimal system or eyelids, and many were the result of trauma or infection. There were no cases of orbital tumor or thyroid eye disease. There were no surgical or anesthesia-related complications. Most patients (80\%) had no documented history of dementia, and only 1 was diabetic. Notably, 33\% of patients presented with no light perception vision in at least 1 eye. CONCLUSIONS: Ophthalmic plastic surgery can be performed safely in select patients 100 years of age and older. Formal prospective studies are needed to improve surgical care in this group.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001174},
	author = {Wolkow, Natalie and Weinberg, David A and Bersani, Thomas A and Yoon, Michael K and Lefebvre, Daniel R and Lee, Nahyoung Grace and Sutula, Francis C and Mandeville, John T and Hatton, Mark P and Freitag, Suzanne K}
}
@article {1430543,
	title = {Orbital Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma: An Ongoing Diagnostic Challenge Further Confounded by Small-Cell Predominance},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {35},
	number = {5},
	year = {2019},
	month = {2019 Sep/Oct},
	pages = {478-483},
	abstract = {PURPOSE: To highlight the histopathologic diagnostic challenges of small-cell predominant extranodal nasal-type natural killer/T-cell lymphoma (ENTNKT) of the orbit. METHODS: Retrospective chart review and histopathologic study with immunohistochemistry and in situ hybridization of 3 cases. RESULTS: Three cases of ENTNKT presented to the Mass Eye and Ear emergency room as orbital cellulitis over 1 year. The first case was unusual in that there was a predominance of small cells, giving the ENTNKT the histopathologic appearance of a nonmalignant inflammatory process. This challenging case is juxtaposed alongside 2 other cases, which exhibited the more typical lymphomatous microscopic appearance. DISCUSSION: ENTNKT can extend into the orbit from the adjacent sinuses or rarely arise primarily in the orbit. A diagnosis is typically made with a biopsy. Occasionally, however, the histopathologic diagnosis can be elusive when a predominance of small lymphomatous cells that are virtually indistinguishable from non-neoplastic inflammatory cells is present. Demonstration of CD56 positivity by immunostaining and in situ hybridization for Epstein-Barr virus are essential in confirming the diagnosis. CONCLUSIONS: ENTNKT should be considered both in the clinical and histopathologic differential diagnoses of orbital infections and idiopathic inflammations (pseudotumor).},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001333},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Habib, Larissa A and Freitag, Suzanne K}
}
@article {1417584,
	title = {Programmed Cell Death 1 Ligand 1 and Programmed Cell Death 1 Ligand 2 Are Expressed in Conjunctival Invasive Squamous Cell Carcinoma: Therapeutic Implications},
	journal = {Am J Ophthalmol},
	volume = {200},
	year = {2019},
	month = {2019 Apr},
	pages = {226-241},
	abstract = {PURPOSE: Novel cancer immunotherapies, called immune checkpoint inhibitors, have demonstrated clinical efficacy in the treatment of squamous cell carcinomas of the head and neck. Tissue expression of programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) has been shown to predict tumor response to these drugs. We examine the expression of prognostic immune biomarkers, PD-L1 and PD-L2, in invasive ocular surface squamous neoplasia. DESIGN: Retrospective case series. METHODS: Eighteen cases of ocular surface or ocular adnexal invasive squamous cell carcinomas were identified in pathology case files of the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary and at the Wills Eye Hospital accessioned between January 1, 2014 and January 1, 2017. Immunohistochemical staining for PD-L1, PD-L2, CD8, and p16 was performed and graded in a standardized fashion. RESULTS: PD-L1 and PD-L2 were expressed on tumor cells to varying degrees, and also on some stromal cells and endothelial cells. Stromal and endothelial cell expression was also seen in control conjunctival specimens. Tumor expression of PD-L1 and PD-L2 was present on the cell membranes. All 18 (100\%) of the tumors expressed PD-L1: 7 (39\%) expressed a high level, 3 (17\%) expressed a medium level, and 8 (44\%) expressed a low level. Only 9 (50\%) tumors expressed PD-L2 and it was at a low level. The expression of PD-L1 in tumor cells correlated with the presence of CD8-positive cytotoxic T lymphocytes among tumor cells (P \&lt; .01) and with the presence of CD8-positive cells in the surrounding stroma (P\&nbsp;= .04). CONCLUSIONS: A subset of ocular invasive conjunctival squamous carcinomas express high levels of PD-L1 and CD8 and therefore may respond therapeutically to immune checkpoint inhibition.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.12.020},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Afrogheh, Amir H and Eagle, Ralph C and Pai, Sara I and Faquin, William C}
}
@article {1295884,
	title = {A Common Procedure With an Uncommon Pathology: Triamcinolone Acetonide Eyelid Injection},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {34},
	number = {3},
	year = {2018},
	month = {2018 May/Jun},
	pages = {e72-e73},
	abstract = {Local corticosteroid injections are frequently employed by ophthalmologists to treat a variety of ocular, periocular, and orbital inflammatory conditions. Triamcinolone acetonide is a slowly dissolving crystalline corticosteroid that is often used for this purpose because of its prolonged anti-inflammatory effect. On occasion, previously injected corticosteroid material persists in tissues longer than anticipated, creating nodules that may masquerade as other disease conditions, or appearing incidentally in excised lesions on histopathologic examination. The histopathologic features of corticosteroid residues are unfamiliar to most ophthalmic pathologists and general pathologists. These features are described herein. Triamcinolone acetonide deposits in the skin appear as pale eosinophilic lakes of acellular frothy material on hematoxylin-eosin staining and are occasionally surrounded by a mild inflammatory reaction.},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000001045},
	author = {Wolkow, Natalie and Jakobiec, Frederick A and Hatton, Mark P}
}
@article {837006,
	title = {Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease: An Analysis of Vascular Growth Factors with Clinical Correlation.},
	journal = {Ophthalmology},
	volume = {123},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {2028-36},
	abstract = {PURPOSE: The human orbit is an environment that is vulnerable to inflammation and edema in the setting of autoimmune thyroid disease. Our study investigated the tenet that orbital adipose tissue lacks lymphatic vessels and analyzed the clinicopathologic differences between patients with acute and chronic thyroid eye disease (TED). The underlying molecular mediators of blood and lymphatic vessel formation within the orbital fat also were evaluated. DESIGN: Retrospective cohort study. PARTICIPANTS: The study included fat specimens from 26 orbits of 15 patients with TED undergoing orbital decompression. Orbital fat specimens from patients without TED as well as cadaveric orbital fat served as controls. METHODS: Tissue specimens were processed as formalin-fixed, paraffin-embedded sections or frozen cryosections for immunohistochemistry. Total RNA was extracted and analyzed via quantitative (real-time) reverse-transcription polymerase chain reaction. Clinicopathologic correlation was made by determining the clinical activity score (CAS) of each patient with TED. MAIN OUTCOME MEASURES: Samples were examined for vascular and lymphatic markers including podoplanin, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and cluster of differentiation 31 (CD31) by immunohistochemistry, as well as for mRNA levels of vascular endothelial growth factor (VEGF), VEGF receptors, semaphorin 3F, neuropilin 1, neuropilin 2, podoplanin, and LYVE-1 by quantitative (real-time) reverse-transcription polymerase chain reaction. RESULTS: Clinicopathologic correlation revealed increased staining of CD31-positive blood vessels in patients with acute TED with a CAS more than 4, as well as rare staining of podoplanin-positive lymphatic vessels within acutely inflamed orbital fat tissue. Additionally, quantitative (real-time) reverse-transcription polymerase chain reaction analysis demonstrated increased expression of VEGF receptor (VEGFR) 2 as well as VEGF signaling molecules VEGF-A, VEGF-C, and VEGF-D. CONCLUSIONS: In acute TED, compared with chronic TED and control orbital fat, there is increased blood vessel density, suggesting neovascularization and rare lymphatic vessels suggestive of limited lymphangiogenesis. This proangiogenic and prolymphangiogenic microenvironment is likely the result of the increased expression of VEGFR-2, VEGF-A, VEGF-C, and VEGF-D. These findings imply that orbital edema in acute TED may be mediated, in part, by both the formation of new, immature blood vessels and the formation of lymphatic capillaries that are functionally incapable of draining interstitial fluid.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.05.052},
	author = {Wong, Lindsay L and Lee, Nahyoung Grace and Amarnani, Dhanesh and Choi, Catherine J and Bielenberg, Diane R and Freitag, Suzanne K and D{\textquoteright}Amore, Patricia A and Kim, Leo A}
}
@article {1318879,
	title = {Guidelines on Diabetic Eye Care: The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings},
	journal = {Ophthalmology},
	volume = {125},
	number = {10},
	year = {2018},
	month = {2018 Oct},
	pages = {1608-1622},
	abstract = {Diabetes mellitus (DM) is a global epidemic and affects populations in both developing and developed countries, with differing health care and resource levels. Diabetic retinopathy (DR) is a major complication of DM and a leading cause of vision loss in working middle-aged adults. Vision loss from DR can be prevented with broad-level public health strategies, but these need to be tailored to a country{\textquoteright}s and population{\textquoteright}s resource setting. Designing DR screening programs, with appropriate and timely referral to facilities with trained eye care professionals, and using cost-effective treatment for vision-threatening levels of DR can prevent vision loss. The International Council of Ophthalmology Guidelines for Diabetic Eye Care 2017 summarize and offer a comprehensive guide for DR screening, referral and follow-up schedules for DR, and appropriate management of vision-threatening DR, including diabetic macular edema (DME) and proliferative DR, for countries with high- and low- or intermediate-resource settings. The guidelines include updated evidence on screening and referral criteria, the minimum requirements for a screening vision and retinal examination, follow-up care, and management of DR and DME, including laser photocoagulation and appropriate use of intravitreal anti-vascular endothelial growth factor inhibitors and, in specific situations, intravitreal corticosteroids. Recommendations for management of DR in patients during pregnancy and with concomitant cataract also are included. The guidelines offer suggestions for monitoring outcomes and indicators of success at a population level.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2018.04.007},
	author = {Wong, Tien Y and Sun, Jennifer and Kawasaki, Ryo and Ruamviboonsuk, Paisan and Gupta, Neeru and Lansingh, Van Charles and Maia, Mauricio and Mathenge, Wanjiku and Moreker, Sunil and Muqit, Mahi M K and Resnikoff, Serge and Verdaguer, Juan and Zhao, Peiquan and Ferris, Frederick and Aiello, Lloyd P and Taylor, Hugh R}
}
@article {1653593,
	title = {Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Injury: Role of Inflammation and Other Factors},
	journal = {Int J Mol Sci},
	volume = {23},
	number = {17},
	year = {2022},
	month = {2022 Sep 05},
	abstract = {The optic nerve, like most pathways in the mature central nervous system, cannot regenerate if injured, and within days, retinal ganglion cells (RGCs), the neurons that extend axons through the optic nerve, begin to die. Thus, there are few clinical options to improve vision after traumatic or ischemic optic nerve injury or in neurodegenerative diseases such as glaucoma, dominant optic neuropathy, or optic pathway gliomas. Research over the past two decades has identified several strategies to enable RGCs to regenerate axons the entire length of the optic nerve, in some cases leading to modest reinnervation of di- and mesencephalic visual relay centers. This review primarily focuses on the role of the innate immune system in improving RGC survival and axon regeneration, and its synergy with manipulations of signal transduction pathways, transcription factors, and cell-extrinsic suppressors of axon growth. Research in this field provides hope that clinically effective strategies to improve vision in patients with currently untreatable losses could become a reality in 5-10 years.},
	keywords = {Axons, Cell Survival, Humans, Inflammation, Nerve Regeneration, Optic Nerve Injuries, Retinal Ganglion Cells},
	issn = {1422-0067},
	doi = {10.3390/ijms231710179},
	author = {Wong, Kimberly A and Benowitz, Larry I}
}
@article {1688221,
	title = {Clonal haematopoiesis and risk of chronic liver disease},
	journal = {Nature},
	volume = {616},
	number = {7958},
	year = {2023},
	month = {2023 Apr},
	pages = {747-754},
	abstract = {Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of\&nbsp;liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95\% confidence interval (95\% CI) [1.46, 2.79]; P \&lt; 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95\% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95\% CI [1.57, 3.6]; P \&lt; 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response.},
	keywords = {Animals, Clonal Hematopoiesis, Fibrosis, Hepatitis, Inflammation, Liver Cirrhosis, Mice, Non-alcoholic Fatty Liver Disease},
	issn = {1476-4687},
	doi = {10.1038/s41586-023-05857-4},
	author = {Wong, Waihay J and Emdin, Connor and Bick, Alexander G and Zekavat, Seyedeh M and Niroula, Abhishek and Pirruccello, James P and Dichtel, Laura and Griffin, Gabriel and Uddin, Md Mesbah and Gibson, Christopher J and Kovalcik, Veronica and Lin, Amy E and McConkey, Marie E and Vromman, Amelie and Sellar, Rob S and Kim, Peter G and Agrawal, Mridul and Weinstock, Joshua and Long, Michelle T and Yu, Bing and Banerjee, Rajarshi and Nicholls, Rowan C and Dennis, Andrea and Kelly, Matt and Po-Ru Loh and McCarroll, Steve and Boerwinkle, Eric and Vasan, Ramachandran S and Jaiswal, Siddhartha and Johnson, Andrew D and Chung, Raymond T and Corey, Kathleen and Levy, Daniel and Ballantyne, Christie and NHLBI TOPMed Hematology Working Group and Ebert, Benjamin L and Natarajan, Pradeep}
}
@article {1732526,
	title = {Author Correction: Clonal haematopoiesis and risk of chronic liver disease},
	journal = {Nature},
	volume = {619},
	number = {7970},
	year = {2023},
	month = {2023 Jul},
	pages = {E47},
	issn = {1476-4687},
	doi = {10.1038/s41586-023-06375-z},
	author = {Wong, Waihay J and Emdin, Connor and Bick, Alexander G and Zekavat, Seyedeh M and Niroula, Abhishek and Pirruccello, James P and Dichtel, Laura and Griffin, Gabriel and Uddin, Md Mesbah and Gibson, Christopher J and Kovalcik, Veronica and Lin, Amy E and McConkey, Marie E and Vromman, Amelie and Sellar, Rob S and Kim, Peter G and Agrawal, Mridul and Weinstock, Joshua and Long, Michelle T and Yu, Bing and Banerjee, Rajarshi and Nicholls, Rowan C and Dennis, Andrea and Kelly, Matt and Po-Ru Loh and McCarroll, Steve and Boerwinkle, Eric and Vasan, Ramachandran S and Jaiswal, Siddhartha and Johnson, Andrew D and Chung, Raymond T and Corey, Kathleen and Levy, Daniel and Ballantyne, Christie and NHLBI TOPMed Hematology Working Group and Ebert, Benjamin L and Natarajan, Pradeep}
}
@article {1364570,
	title = {Macular imaging for glaucoma using spectral-domain optical coherence tomography: a review},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {5-6},
	year = {2012},
	month = {2012 Sep-Nov},
	pages = {160-6},
	abstract = {Since its introduction, optical coherence tomography (OCT) has become widely used and accepted as an imaging modality to detect and follow glaucoma, with measurement of the peripapillary retinal nerve fiber layer (pRNFL) being the most utilized parameter. Up until recently, macular thickness parameters have not been commonly used in glaucoma due to results of earlier studies with time-domain OCT (TD-OCT) that revealed macular imaging to be inferior to pRNFL in the diagnosis of glaucoma. The recent advent of spectral-domain OCT (SD-OCT) has renewed interest in the potential uses of macular imaging in glaucoma due to its ability to better segment and measure individual retinal layers. Multiple studies have been performed in the last few years to investigate the diagnostic ability, reproducibility, and limitations of these new SD-OCT macular parameters. The purpose of this paper is to review the findings of those studies to assess the current utility of macular SD-OCT in glaucoma. Overall, SD-OCT has been shown to have higher reproducibility than TD-OCT, and though there have been some conflicting reports, the majority of studies seem to concur that the diagnostic sensitivity of SD-OCT macular parameters is at least comparable to TD-OCT and other SD-OCT parameters.},
	keywords = {Glaucoma, Humans, Nerve Fibers, Optic Disk, Optic Nerve Diseases, Reproducibility of Results, Retinal Ganglion Cells, Tomography, Optical Coherence},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.712734},
	author = {Wong, Jessica J and Chen, Teresa C and Shen, Lucy Q and Pasquale, Louis R}
}
@article {1532366,
	title = {HIV-induced Retinitis},
	journal = {Ocul Immunol Inflamm},
	volume = {28},
	number = {8},
	year = {2020},
	month = {2020 Nov 16},
	pages = {1259-1268},
	abstract = {PURPOSE: To provide an overview of the current knowledge on the Human Immunodeficiency Virus (HIV)-associated retinopathies. METHODS: A PubMed search was performed, using the key terms "HIV Retinopathy OR Retinitis" and "HIV AND Retinitis" to find manuscripts published within the last ten years. RESULTS: If left untreated, HIV infection causes a progressive immunodeficiency caused by depletion of CD4-positive T lymphocytes. Noninfectious HIV retinopathy, clinically manifested by cotton wool spots. Once the CD4 count drops below 200\&nbsp;c/μl, immunodeficiency creates a vulnerability for systemic opportunistic infections. Within the posterior segment of the eye, cytomegalovirus (CMV) retinitis has to be distinguished from infections with other members of the herpes virus family, as well as from toxoplasmosis, tuberculosis, and syphilis. Upon restoration of the immune system, immune recovery uveitis may manifest in one third of CMV affected eyes. CONCLUSION: Targeted antiviral treatment and secondary recurrence prophylaxis prevent vision loss of the retina prior to immune recovery.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2020.1808225},
	author = {Wons, Juliana and Kempen, John and Garweg, Justus G}
}
@article {1748531,
	title = {Upper portion of the eyelid blepharoplasty for a patient with recalcitrant Morbihan disease},
	journal = {JAAD Case Rep},
	volume = {38},
	year = {2023},
	month = {2023 Aug},
	pages = {102-104},
	issn = {2352-5126},
	doi = {10.1016/j.jdcr.2023.06.004},
	author = {Woodbury, Michael J and Chen, Stella X and Stagner, Anna M and Lee, Nahyoung G and Merola, Joseph F}
}
@article {988056,
	title = {Characterization of Multi-Drug Resistant Enterococcus faecalis Isolated from Cephalic Recording Chambers in Research Macaques (Macaca spp.).},
	journal = {PLoS One},
	volume = {12},
	number = {1},
	year = {2017},
	pages = {e0169293},
	abstract = {Nonhuman primates are commonly used for cognitive neuroscience research and often surgically implanted with cephalic recording chambers for electrophysiological recording. Aerobic bacterial cultures from 25 macaques identified 72 bacterial isolates, including 15 Enterococcus faecalis isolates. The E. faecalis isolates displayed multi-drug resistant phenotypes, with resistance to ciprofloxacin, enrofloxacin, trimethoprim-sulfamethoxazole, tetracycline, chloramphenicol, bacitracin, and erythromycin, as well as high-level aminoglycoside resistance. Multi-locus sequence typing showed that most belonged to two E. faecalis sequence types (ST): ST 4 and ST 55. The genomes of three representative isolates were sequenced to identify genes encoding antimicrobial resistances and other traits. Antimicrobial resistance genes identified included aac(6{\textquoteright})-aph(2"), aph(3{\textquoteright})-III, str, ant(6)-Ia, tetM, tetS, tetL, ermB, bcrABR, cat, and dfrG, and polymorphisms in parC (S80I) and gyrA (S83I) were observed. These isolates also harbored virulence factors including the cytolysin toxin genes in ST 4 isolates, as well as multiple biofilm-associated genes (esp, agg, ace, SrtA, gelE, ebpABC), hyaluronidases (hylA, hylB), and other survival genes (ElrA, tpx). Crystal violet biofilm assays confirmed that ST 4 isolates produced more biofilm than ST 55 isolates. The abundance of antimicrobial resistance and virulence factor genes in the ST 4 isolates likely relates to the loss of CRISPR-cas. This macaque colony represents a unique model for studying E. faecalis infection associated with indwelling devices, and provides an opportunity to understand the basis of persistence of this pathogen in a healthcare setting.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0169293},
	author = {Woods, Stephanie E and Lieberman, Mia T and Lebreton, Francois and Trowel, Elise and de la Fuente-N{\'u}{\~n}ez, C{\'e}sar and Dzink-Fox, Joanne and Gilmore, Michael S and Fox, James G}
}
@article {1363224,
	title = {Binding of transmembrane mucins to galectin-3 limits herpesvirus 1 infection of human corneal keratinocytes},
	journal = {J Virol},
	volume = {87},
	number = {10},
	year = {2013},
	month = {2013 May},
	pages = {5841-7},
	abstract = {Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx.},
	keywords = {Galectin 3, Herpesvirus 1, Human, Humans, Keratinocytes, Mucins, Protein Binding, Receptors, Virus, Virus Attachment},
	issn = {1098-5514},
	doi = {10.1128/JVI.00166-13},
	author = {Woodward, A M and Mauris, J and Arg{\"u}eso, P}
}
@article {314221,
	title = {Expression analysis of the transmembrane mucin MUC20 in human corneal and conjunctival epithelia},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {55},
	number = {10},
	year = {2014},
	month = {2014 Aug 28},
	pages = {6132-8},
	abstract = {PURPOSE: Cell surface mucins are a group of highly O-glycosylated transmembrane glycoproteins responsible for the protection of epithelial cells on mucosal surfaces. The aim of this study was to investigate the localization and regulation of mucin 20 (MUC20) at the ocular surface. METHODS: Localization of MUC20 in human corneal and conjunctival epithelia was evaluated by immunofluorescence microscopy. Immortalized corneal (HCLE) and conjunctival (HCjE) cell lines were grown at different stages of differentiation and subjected to quantitative PCR and Western blot analyses. Cell surface proteins on apical cell membranes were biotinylated and isolated by neutravidin chromatography. RESULTS: The MUC20 was detected throughout the entire human ocular surface epithelia, predominantly in cell membranes within intermediate cell layers. In conjunctiva, MUC20 also was observed in the cytoplasm of apical cells within the stratified squamous epithelium, but not in goblet cells. Quantitative PCR and immunoblotting demonstrated expression of MUC20 in HCLE and HCjE cells. Induction of differentiation with serum-containing medium resulted in upregulation of MUC20 mRNA and protein. Biotin labeling of the surface of stratified cultures revealed low levels of MUC20 protein on apical glycocalyces. Further, MUC20 was not detected in the cell culture media or in human tears, suggesting that the extracellular domain of MUC20 is not released from the ocular surface as described previously for other cell surface mucins. CONCLUSIONS: Our results indicate that MUC20 is a novel transmembrane mucin expressed by the human corneal and conjunctival epithelia, and suggest that differential expression of MUC20 during differentiation has a role in maintaining ocular surface homeostasis.},
	keywords = {Blotting, Western, Cell Differentiation, Cell Line, Conjunctiva, Electrophoresis, Polyacrylamide Gel, Epithelium, Corneal, Gene Expression Regulation, Humans, Microscopy, Fluorescence, Mucins, Polymerase Chain Reaction, RNA, Messenger},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15269},
	author = {Woodward, Ashley M and Arg{\"u}eso, Pablo}
}
@article {1364571,
	title = {Characterization of the interaction between hydroxypropyl guar galactomannan and galectin-3},
	journal = {Biochem Biophys Res Commun},
	volume = {424},
	number = {1},
	year = {2012},
	month = {2012 Jul 20},
	pages = {12-7},
	abstract = {Multivalent galactose ligands have been proposed for selective targeting of carbohydrate-binding proteins on epithelial cell surfaces, both in normal and pathological conditions. One cellular partner is galectin-3, a β-galactoside-binding protein present on many epithelial linings, such as those of the ocular surface. In this study, we investigated the ability of hydroxypropyl guar galactomannan (HPGG) to bind recombinant galectin-3 and to target the apical surface of differentiated human corneal keratinocytes. Pull-down and slot-blot assays demonstrated that fluorescence-labeled HPGG bound recombinant galectin-3 through a galactose-dependent mechanism. In contrast, no binding of HPGG could be detected towards recombinant galectin-8 or -9. In a cell culture system, HPGG bound weakly to biotinylated cell surface corneal isolates containing endogenous galectin-3, and incubation of HPGG with corneal keratinocytes in culture resulted in discrete, galactose-independent, binding to the cell surface. Moreover, HPGG failed to elute the biological counter-receptor MUC16 from galectin-3 affinity columns. We conclude that HPGG binds galectin-3 through the conventional carbohydrate-recognition domain in vitro, but not in a biological system, suggesting that endogenous carbohydrate ligands on epithelial cell surface glycocalyces impair HPGG biorecognition.},
	keywords = {CA-125 Antigen, Cell Line, Cornea, Galactose, Galectin 3, Humans, Keratinocytes, Mannans, Membrane Proteins},
	issn = {1090-2104},
	doi = {10.1016/j.bbrc.2012.05.160},
	author = {Woodward, Ashley M and Senchyna, Michelle and Williams, Ravaughn and Arg{\"u}eso, Pablo}
}
@article {1360126,
	title = {Inflammatory Stress Causes N-Glycan Processing Deficiency in Ocular Autoimmune Disease},
	journal = {Am J Pathol},
	volume = {189},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {283-294},
	abstract = {High levels of proinflammatory cytokines have been associated with a loss of tissue function in ocular autoimmune diseases, but the basis for this relationship remains poorly understood. Here we investigate a new role for tumor necrosis factor α in promoting N-glycan-processing deficiency at the surface of the eye through inhibition of N-acetylglucosaminyltransferase expression in the Golgi. Using mass spectrometry, complex-type biantennary oligosaccharides were identified as major N-glycan structures in differentiated human corneal epithelial cells. Remarkably, significant differences were detected between the efficacies of cytokines in regulating the expression of glycogenes involved in the biosynthesis of N-glycans. Tumor necrosis factor α but not IL-1β had a profound effect in suppressing the expression of enzymes involved in the Golgi branching pathway, including N-acetylglucosaminyltransferases 1 and 2, which are required for the formation of biantennary structures. This decrease in gene expression was correlated with a reduction in enzymatic activity and impaired N-glycan branching. Moreover, patients with ocular mucous membrane pemphigoid were characterized by marginal N-acetylglucosaminyltransferase expression and decreased N-glycan branching in the conjunctiva. Together, these data indicate that proinflammatory cytokines differentially influence the expression of N-glycan-processing enzymes in the Golgi and set the stage for future studies to explore the pathophysiology of ocular autoimmune diseases.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2018.10.012},
	author = {Woodward, Ashley M and Lehoux, Sylvain and Mantelli, Flavio and Di Zazzo, Antonio and Brockhausen, Inka and Bonini, Stefano and Arg{\"u}eso, Pablo}
}
@article {1490452,
	title = {Endoplasmic reticulum stress promotes inflammation-mediated proteolytic activity at the ocular surface},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Feb 10},
	pages = {2216},
	abstract = {A growing body of evidence implicates endoplasmic reticulum (ER) stress in the pathogenesis of chronic inflammatory and autoimmune disorders. Here, we demonstrate that the proinflammatory cytokine TNFα stimulates matrix metalloproteinase 9 (MMP9) at the ocular surface through a c-Fos-dependent mechanism of ER stress. We found positive reactivity of the molecular chaperone BiP/GRP78 in conjunctival epithelium of patients with ocular cicatricial pemphigoid and increased levels of BiP/GRP78, sXBP1 and GRP94 in human corneal epithelial cells treated with TNFα. Pharmacological blockade of ER stress in vitro using dexamethasone or the chemical chaperones TUDCA and 4PBA attenuated MMP9 expression and secretion in the presence of TNFα. Moreover, expression analysis of genes associated with inflammation and autoimmunity identified the c-Fos proto-oncogene as a mediator of ER stress responses in epithelial cells. Substantially less TNFα-induced MMP9 expression occurred when c-Fos signaling was suppressed with a function-blocking antibody. Taken together, these results indicate that activation of ER stress contributes to promote inflammation-mediated proteolytic activity and uncovers a target for restoring tissue homeostasis in ocular autoimmune disease.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-59237-3},
	author = {Woodward, Ashley M and Di Zazzo, Antonio and Bonini, Stefano and Arg{\"u}eso, Pablo}
}
@article {1573114,
	title = {Short-Term Reproducibility of MUC5AC Measurement in Human Tear Fluid},
	journal = {Diagnostics (Basel)},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Jan 02},
	abstract = {The assessment of tear fluid components is a common and valuable approach to understanding ocular surface disease and testing the efficacy of novel therapeutic strategies. However, the interpretation and utility of the findings can be limited by changes in the composition of the tear film, particularly in studies requiring repetitive patient sampling. Here, tear samples were collected twice within a one-hour interval to evaluate the short-term reproducibility of an immunoassay aimed to measure the amount of MUC5AC mucin. We found no statistical difference in total protein or MUC5AC content between the two consecutive collections of tear fluid, although the inter-individual variability in each group was high, with coefficients of variation exceeding 30\% and 50\%, respectively. Scatterplots showed a significant correlation in both protein and MUC5AC following collection within a one-hour interval. These data indicate that, regardless of the high inter-individual variability, repeated collection of tear fluid within an hour interval produces reproducible intra-individual data in terms of MUC5AC mucin content, and suggest that the normal mucin composition of the tear fluid can be re-established within an hour of the initial collection.},
	issn = {2075-4418},
	doi = {10.3390/diagnostics11010057},
	author = {Woodward, Ashley M and Senchyna, Michelle and Arg{\"u}eso, Pablo}
}
@article {1623369,
	title = {CRISPR/Cas9 genome editing reveals an essential role for basigin in maintaining a nonkeratinized squamous epithelium in cornea},
	journal = {FASEB Bioadv},
	volume = {3},
	number = {11},
	year = {2021},
	month = {2021 Nov},
	pages = {897-908},
	abstract = {One of the primary functions of nonkeratinized stratified squamous epithelia is to protect underlying tissues against chemical, microbial, and mechanical insult. Basigin is a transmembrane matrix metalloproteinase inducer commonly overexpressed during epithelial wound repair and cancer but whose physiological significance in normal epithelial tissue has not been fully explored. Here we used a CRISPR/Cas9\&nbsp;system to study the effect of basigin loss in a human cornea model of squamous epithelial differentiation. We find that epithelial cell cultures lacking basigin change shape and fail to produce a flattened squamous layer on the apical surface. This process is associated with the abnormal expression of the transcription factor SPDEF and the decreased biosynthesis of MUC16 and involucrin necessary for maintaining apical barrier function and structural integrity, respectively. Expression analysis of genes encoding tight junction proteins identified a role for basigin in promoting physiological expression of occludin and members of the claudin family. Functionally, disruption of basigin expression led to increased epithelial cell permeability as evidenced by the decrease in transepithelial electrical resistance and increase in rose bengal flux. Overall, these results suggest that basigin plays a distinct role in maintaining the normal differentiation of stratified squamous human corneal epithelium and could have potential implications to therapies targeting basigin function.},
	issn = {2573-9832},
	doi = {10.1096/fba.2021-00067},
	author = {Woodward, Ashley M and Feeley, Marissa N and Rinaldi, Jamie and Arg{\"u}eso, Pablo}
}
@article {1653580,
	title = {Enhancing Diversity in the Ophthalmology Workforce},
	journal = {Ophthalmology},
	volume = {129},
	number = {10},
	year = {2022},
	month = {2022 10},
	pages = {e127-e136},
	abstract = {Health care teams are most effective at addressing complex problems and improving health outcomes for underserved populations when team members bring diverse life experiences and perspectives to the effort. With rates of visual impairment expected to increase in the United States by 2050, especially among minority populations, diversification of the ophthalmology workforce will be critical in reducing disparities in access to and quality of vision health care. Currently, ophthalmology is less diverse with respect to race, ethnicity, and gender than graduating medical classes and other medical specialties, as well as the general US population. In addition, data on diversity in sexual orientation and gender identity, socioeconomic status, and disability are lacking in ophthalmology. The Minority Ophthalmology Mentoring and Rabb-Venable Excellence in Ophthalmology Programs are examples of initiatives to increase racial and ethnic diversity in the workforce and can serve as models for increasing other aspects of inclusiveness. Other strategies for improving vision health care for all Americans include continuing to support existing diversity programs and creating new ones; addressing unconscious and implicit bias in medical school, residency, and faculty selections; conducting holistic reviews of medical school and residency applications; diversifying selection committees and leadership; and encouraging faculty development of underrepresented groups.},
	keywords = {Cultural Diversity, Female, Gender identity, Humans, Male, Minority Groups, Ophthalmology, United States, Workforce},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.06.033},
	author = {Woreta, Fasika A and Gordon, Lynn K and Knight, O{\textquoteright}Rese J and Randolph, Jessica D and Zebardast, Nazlee and P{\'e}rez-Gonz{\'a}lez, C{\'e}sar E}
}
@article {1806686,
	title = {Risk Factors for Meeting Criteria for Switching from Bevacizumab to Aflibercept When Treating Eyes with Diabetic Macular Edema and Visual Acuity},
	journal = {Ophthalmology},
	year = {2024},
	month = {2024 Feb 07},
	abstract = {OBJECTIVE: To identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network Protocol AC. DESIGN: Post hoc analysis of data from a randomized clinical trial PARTICIPANTS: 270 participants with one or both eyes with CI-DME and visual acuity (VA) letter score of 69 to 24 (Snellen equivalent 20/50-20/320) METHODS: Eligible eyes were assigned to receive intravitreal aflibercept monotherapy (N=158) or bevacizumab followed by aflibercept if prespecified criteria for switching were met between 12 weeks and 2 years (N=154). MAIN OUTCOME MEASURES: Meeting switching criteria: 1) at any time, 2) at 12 weeks, and 3) after 12 weeks. Associations between meeting the criteria for switching and factors measured at baseline and 12 weeks were evaluated in univariable analyses. Stepwise procedures were used to select variables for multivariable models. RESULTS: In the bevacizumab first group, older participants had higher risk of meeting the switching criteria at any time, with a hazard ratio (HR) for a 10-year increase in age (95\% confidence interval) of 1.32 (1.11 - 1.58). Male participants or eyes with worse baseline VA were more likely to switch at 12 weeks (HR for male vs. female = 4.84 [1.32 - 17.81]; HR for 5-letter lower baseline VA: 1.30 [1.03 - 1.63]). Worse 12-week CST (HR for 10-μm greater = 1.06 [1.04 - 1.07]) was associated with increased risk for switching after 12 weeks. The mean (SD) improvement after completing the switch to aflibercept was 3.7 (4.9) letters. CONCLUSIONS: The identified factors can be used to refine expectations regarding the likelihood that an eye will meet protocol criteria to switch to aflibercept when treatment is initiated with bevacizumab. Older patients are more likely to be switched. At twelve weeks, thicker central subfield thickness was predictive of eyes most likely to be switched in the future.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2024.01.037},
	author = {Writing Committee and Jhaveri, Chirag D and Liu, Danni and Maguire, Maureen G and Glassman, Adam R and Grigorian, Ruben A and Jampol, Lee M and Kingsley, Ronald M and MacCumber, Mathew W and Martin, Daniel F and Maturi, Raj K and Velez, Gisela and Sun, Jennifer K and DRCR Retina Network}
}
@article {1806656,
	title = {Outcomes of Boston Keratoprosthesis Type I Implantation in Poland: A Retrospective Study on 118 Patients},
	journal = {J Clin Med},
	volume = {13},
	number = {4},
	year = {2024},
	month = {2024 Feb 08},
	abstract = {Background: Boston Keratoprosthesis Type I (BI-KPro I) is a synthetic cornea that can be used to restore vision in patients with corneal blindness. This retrospective study evaluated the outcomes of BI-KPro implantation in 118 patients. Material: The mean age of the patients was 56.76 {\textpm} 14.24 years. Indications for keratoprosthesis implantation were as follows: graft failure, 47 (39.83\%); ocular burn, 38 (32.20\%); neurotrophic keratopathy, 11 (9.32\%), mucous membrane pemphigoid 9 (7.67\%); autoimmune, 6 (5.08\%); Stevens-Johnson syndrome, 4 (3.39\%); and aniridia (2.54\%). Methods: The surgeries were performed between March 2019 and June 2022 at a single clinical center in two locations. The postoperative visual acuity, complications, and need for additional surgical procedures were analyzed. Results: The Best Corrected Visual Acuity before surgery was 0.01 {\textpm} 0.006. After one year (V1), it was 0.30 {\textpm} 0.27; at two years (V2), it was 0.27 {\textpm} 0.26; and at three years (V3), it was 0.21 {\textpm} 0.23. The percentage of patients with visual acuity better than 0.1 on the Snellen chart was 37.29\% after 1 year, 49.35\% after 2 years, and 46.81\% after 3 years of follow up. The most common complications were glaucoma (78 patients; 66.1\%), corneal melting (22 patients; 18.6\%), and retroprosthetic membranes (20 patients; 17.0\%). Conclusions: The BI-KPro can significantly improve visual acuity. The worst long-term results were obtained in the group of patients with autoimmune diseases; therefore, careful consideration should be given to implanting BI-KPro in this group. The high incidence of de novo glaucoma or the progression of pre-existing glaucoma suggests the need for careful monitoring.},
	issn = {2077-0383},
	doi = {10.3390/jcm13040975},
	author = {Wr{\'o}blewska-Czajka, Ewa and Dobrowolski, Dariusz and Wyl{\k e}ga{\l}a, Adam and Jurkunas, Ula V and Wyl{\k e}ga{\l}a, Edward}
}
@article {1664953,
	title = {Modulation of Lymphangiogenesis in Incisional Murine Diabetic Wound Healing Using Negative Pressure Wound Therapy},
	journal = {Adv Wound Care (New Rochelle)},
	volume = {12},
	number = {9},
	year = {2023},
	month = {2023 Sep},
	pages = {483-497},
	abstract = {Objective: Despite the significant function of lymphatics in wound healing, and frequent clinical use of Negative Pressure Wound Therapy (NPWT), the effect of mechanical force application on lymphangiogenesis remains to be elucidated. We utilize a murine incisional wound healing model to assess the mechanisms of lymphangiogenesis following NPWT. Approach: Dorsal incisional skin wounds were created on diabetic mice (genetically obese leptin receptor-deficient mice [db/db]; n = 30) and covered with an occlusive dressing (Control, n = 15) or NPWT (-125 mmHg, continuous, 24 h for 7 days; NPWT, n = 15). The wounds were macroscopically assessed for 28 days. Tissue was harvested on day 10 for analysis. Qualitative functional analysis of lymphatic drainage was performed on day 28 using Evans Blue staining (n = 2). Results: NPWT increased lymphatic vessel density (40 {\textpm} 20 vs. 12 {\textpm} 6 podoplanin [PDPN]+ and 25 {\textpm} 9 vs. 14 {\textpm} 8 lymphatic vessel endothelial receptor 1 [LYVE-1]+) and vessel diameter (28 {\textpm} 9 vs. 12 {\textpm} 2 μm). Western blotting verified the upregulation of LYVE-1 with NPWT. Leukocyte presence was higher with NPWT (22\% {\textpm} 3.7\% vs. 9.1\% {\textpm} 4.1\% lymphocyte common antigen [CD45]+) and the leukocytes were predominately B cells clustered within vessels (8.8\% {\textpm} 2.5\% vs. 18\% {\textpm} 3.6\% B-lymphocyte antigen CD20 [CD20]+). Macrophage presence was lower in the NPWT group. Lymphatic drainage was increased in the NPWT group, which exhibited greater Evans Blue positivity. Innovation: The lymphangiogenic effects take place independent of macrophage infiltration, appearing to correlate with B cell presence. Conclusion: NPWT promotes lymphangiogenesis in incisional wounds, significantly increasing the lymph vessel density and diameter. This study highlights the potential of NPWT to stimulate lymphatic drainage and wound healing of surgical incisions.},
	keywords = {Animals, Diabetes Mellitus, Experimental, Evans Blue, Lymphangiogenesis, Mice, Negative-Pressure Wound Therapy, Wound Healing},
	issn = {2162-1918},
	doi = {10.1089/wound.2022.0074},
	author = {Wu, Mengfan and Matar, Dany Y and Yu, Zhen and Chen, Ziyu and Knoedler, Samuel and Ng, Brian and Darwish, Oliver and Haug, Valentin and Friedman, Leigh and Orgill, Dennis P and Panayi, Adriana C}
}
@article {1688246,
	title = {Negative-Pressure Wound Therapy Induces Lymphangiogenesis in Murine Diabetic Wound Healing},
	journal = {Plast Reconstr Surg},
	volume = {151},
	number = {4},
	year = {2023},
	month = {2023 Apr 01},
	pages = {779-790},
	abstract = {BACKGROUND: Decreased lymphangiogenesis contributes to impaired diabetic wound healing. Although negative-pressure wound therapy (NPWT) has been shown to be effective in the treatment of recalcitrant wounds, its impact on lymphangiogenesis remains to be elucidated. In this study, the authors investigate the mechanisms of lymphangiogenesis following NPWT treatment of diabetic murine wound healing. METHODS: Full-thickness dorsal skin wounds (1 {\texttimes} 1 cm 2 ) were excised on 30 db/db mice. The mice were either treated with occlusive covering (control group, n = 15), or received a 7-day treatment of continuous NPWT at -125 mmHg (NPWT group, n = 15). The wounds were photographed on days 0, 7, 10, 14, 21, and 28. Wound tissue was harvested on days 10, 14, 21, and 28 for quantitative analysis. Functional analysis of lymphatic drainage was performed on days 14 and 28 with Evans blue dye tracing. RESULTS: Lymphatic density and diameter, as visualized through podoplanin probing, was significantly higher in the NPWT group compared to the control group ( P \&lt; 0.001). NPWT up-regulated the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) at the protein level ( P = 0.04), and significant differences were noted in lymphatic density as assessed by LYVE-1 staining ( P = 0.001). Leukocyte infiltration was significantly higher in the NPWT group ( P = 0.01). A higher speed of wound closure ( P \&lt; 0.0001) and greater wound bed thickness ( P \&lt; 0.0001) were noted in the NPWT group compared to the control group. CONCLUSIONS: NPWT increased the lymphatic vessel density and diameter with LYVE-1 up-regulation. NPWT therefore plays a positive role in lymphangiogenesis in diabetic wound healing. CLINICAL RELEVANCE STATEMENT: The authors{\textquoteright} study investigates the association of NPWT and lymphatics and underlines the importance of a more in-depth investigation of the role of lymphatic vessels in wound healing.},
	keywords = {Animals, Diabetes Mellitus, Lymphangiogenesis, Mice, Negative-Pressure Wound Therapy, Soft Tissue Injuries, Wound Healing},
	issn = {1529-4242},
	doi = {10.1097/PRS.0000000000009997},
	author = {Wu, Mengfan and Liu, Qinxin and Yu, Zhen and Karvar, Mehran and Aoki, Shimpo and Hamaguchi, Ryoko and Ma, Chenhao and Orgill, Dennis P and Panayi, Adriana C}
}
@article {1282166,
	title = {AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {14},
	year = {2017},
	month = {2017 Dec 01},
	pages = {6082-6090},
	abstract = {Purpose: Pathologic angiogenesis is a component of many diseases, including neovascular age-related macular degeneration, proliferation diabetic retinopathy, as well as tumor growth and metastasis. The purpose of this project was to examine whether the system of adeno-associated viral (AAV)-mediated CRISPR (clustered regularly interspaced short palindromic repeats)-associated endonuclease (Cas)9 can be used to deplete expression of VEGF receptor 2 (VEGFR2) in human vascular endothelial cells in vitro and thus suppress its downstream signaling events. Methods: The dual AAV system of CRISPR/Cas9 from Streptococcus pyogenes (AAV-SpGuide and -SpCas9) was adapted to edit genomic VEGFR2 in primary human retinal microvascular endothelial cells (HRECs). In this system, the endothelial-specific promoter for intercellular adhesion molecule 2 (ICAM2) was cloned into the dual AAV vectors of SpGuide and SpCas9 for driving expression of green fluorescence protein (GFP) and SpCas9, respectively. These two AAV vectors were applied to production of recombinant AAV serotype 5 (rAAV5), which were used to infect HRECs for depletion of VEGFR2. Protein expression was determined by Western blot; and cell proliferation, migration, as well as tube formation were examined. Results: AAV5 effectively infected vascular endothelial cells (ECs) and retinal pigment epithelial (RPE) cells; the ICAM2 promoter drove expression of GFP and SpCas9 in HRECs, but not in RPE cells. The results showed that the rAAV5-CRISPR/Cas9 depleted VEGFR2 by 80\% and completely blocked VEGF-induced activation of Akt, and proliferation, migration as well as tube formation of HRECs. Conclusions: AAV-CRISRP/Cas9-mediated depletion of VEGFR2 is a potential therapeutic strategy for pathologic angiogenesis.},
	keywords = {Blotting, Western, Cell Proliferation, Cells, Cultured, Clustered Regularly Interspaced Short Palindromic Repeats, DNA, Endothelium, Vascular, Gene Expression Regulation, Humans, Polymerase Chain Reaction, Retinal Vessels, RNA, Long Noncoding, Signal Transduction, Vascular Endothelial Growth Factor Receptor-2, Wet Macular Degeneration},
	issn = {1552-5783},
	doi = {10.1167/iovs.17-21902},
	author = {Wu, Wenyi and Duan, Yajian and Ma, Gaoen and Zhou, Guohong and Windhol, Cindy and D{\textquoteright}Amore, Patricia A and Lei, Hetian}
}
@article {1573131,
	title = {Nrf2 overexpression rescues the RPE in mouse models of retinitis pigmentosa},
	journal = {JCI Insight},
	volume = {6},
	number = {2},
	year = {2021},
	month = {2021 Jan 25},
	abstract = {Nrf2, a transcription factor that regulates the response to oxidative stress, has been shown to rescue cone photoreceptors and slow vision loss in mouse models of retinal degeneration (rd). The retinal pigment epithelium (RPE) is damaged in these models, but whether it also could be rescued by Nrf2 has not been previously examined. We used an adeno-associated virus (AAV) with an RPE-specific (Best1) promoter to overexpress Nrf2 in the RPE of rd mice. Control rd mice showed disruption of the regular array of the RPE, as well as loss of RPE cells. Cones were lost in circumscribed regions within the cone photoreceptor layer. Overexpression of Nrf2 specifically in the RPE was sufficient to rescue the RPE, as well as the disruptions in the cone photoreceptor layer. Electron microscopy showed compromised apical microvilli in control rd mice but showed preserved microvilli in Best1-Nrf2-treated mice. The rd mice treated with Best1-Nrf2 had slightly better visual acuity. Transcriptome profiling showed that Nrf2 upregulates multiple oxidative defense pathways, reversing declines seen in the glutathione pathway in control rd mice. In summary, Nrf2 overexpression in the RPE preserves RPE morphology and survival in rd mice, and it is a potential therapeutic for diseases involving RPE degeneration, including age-related macular degeneration (AMD).},
	issn = {2379-3708},
	doi = {10.1172/jci.insight.145029},
	author = {Wu, David M and Ji, Xuke and Ivanchenko, Maryna V and Chung, Michelle and Piper, Mary and Rana, Parimal and Wang, Sean K and Xue, Yunlu and West, Emma and Zhao, Sophia R and Xu, Hongbin and Cicconet, Marcelo and Xiong, Wenjun and Cepko, Constance L}
}
@article {1580504,
	title = {Bilateral anterior segment dysgenesis and peripheral avascular retina with tractional retinal detachment in an infant with multiple congenital anomalies-hypotony-seizures syndrome 3},
	journal = {Ophthalmic Genet},
	volume = {42},
	number = {3},
	year = {2021},
	month = {2021 Jun},
	pages = {334-337},
	abstract = {Background: Multiple congenital anomalies-hypotony-seizures syndrome 3 (MCAHS3) is a rare autosomal recessive disorder caused by mutations in the PIGT gene. PIGT encodes phosphatidylinositol-glycan biosynthesis class T, which plays a crucial role in protein anchoring to cell membranes. The clinical presentation of MCAHS3 is variable in expression and severity, but can be characterized by developmental delay, seizures, hypotonia, facial dysmorphism, and other abnormalities.Materials and Methods: Case report.Results: We report unusual ocular findings including bilateral anterior segment dysgenesis, avascular retinal periphery, and tractional retinal detachment in a 1-month-old male infant with compound heterozygous PIGT mutations consistent with MCAHS3. Whole-exome sequencing did not detect any other genetic abnormalities.Conclusions: This case expands the clinical spectrum of MCAHS3 to include anomalies in ocular anterior segment and retinal vascular development. Given the rarity and the genetic heterogeneity of MCAHS3, giving rise to varied non-ocular phenotypes, it is possible that milder intraocular phenotypes could have gone unrecognized in the past.},
	issn = {1744-5094},
	doi = {10.1080/13816810.2021.1888133},
	author = {Wu, Frances and Goldenberg, Paula C and Mukai, Shizuo}
}
@article {1709681,
	title = {Durable recovery from amblyopia with donepezil},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Jun 22},
	pages = {10161},
	abstract = {An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings, we sought to determine whether donepezil, a commercially available AChEI, can enable recovery in older children and adults with residual amblyopia. In this open-label pilot efficacy study, 16 participants (mean age 16\&nbsp;years; range 9-37\&nbsp;years) with residual anisometropic and/or strabismic amblyopia were treated with daily oral donepezil for 12\&nbsp;weeks. Donepezil dosage was started at 2.5 or 5.0\&nbsp;mg based on age and increased by 2.5\&nbsp;mg if the amblyopic eye visual acuity did not improve by 1 line from the visit 4\&nbsp;weeks prior for a maximum dosage of 7.5 or 10\&nbsp;mg. Participants \&lt; 18\&nbsp;years of age further patched the dominant eye. The primary outcome was visual acuity in the amblyopic eye at 22\&nbsp;weeks, 10\&nbsp;weeks after treatment was discontinued. Mean amblyopic eye visual acuity improved 1.2 lines (range 0.0-3.0), and 4/16 (25\%) improved by >= 2 lines after 12\&nbsp;weeks of treatment. Gains were maintained 10\&nbsp;weeks after cessation of donepezil and were similar for children and adults. Adverse events were mild and self-limited. Residual amblyopia improves in older children and adults treated with donepezil, supporting the concept that the critical window of visual cortical plasticity can be pharmacologically manipulated to treat amblyopia. Placebo-controlled studies are needed.},
	keywords = {Acetylcholinesterase, Amblyopia, Animals, Donepezil, Mice, Visual Acuity},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-34891-5},
	author = {Wu, Carolyn and Gaier, Eric D and Nihalani, Bharti R and Whitecross, Sarah and Takao K Hensch and Hunter, David G}
}
@article {1664989,
	title = {Racial Disparities Affecting Black Patients in Glaucoma Diagnosis and Management},
	journal = {Semin Ophthalmol},
	year = {2023},
	month = {2023 Jan 20},
	pages = {1-11},
	abstract = {Black patients are more affected by glaucoma and suffer from more advanced disease. Diagnostic challenges among black patients with glaucoma include lower rates of diagnostic testing and thinner average central corneal thickness, the latter of which affects intraocular pressure measurement. Treatment challenges include poor follow-up, medication adherence, and trust in providers. Black patients undergoing trabeculectomy have higher rates of failure compared to white patients. Race is not a definitive factor affecting success for tube shunts, laser trabeculoplasty, cyclophotocoagulation, and micro-invasive glaucoma surgeries, but the body of evidence is limited by low inclusion of black patients in these studies. Future steps should include increased attention toward improving trust between patients and providers, improving access to care, and increased representation of black patients in glaucoma research to better understand factors affecting racial disparities in glaucoma management and outcomes in this population disproportionately affected by the disease.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2168489},
	author = {Wu, Annie M and Shen, Lucy Q}
}
@article {1328909,
	title = {Progress in the application of CRISPR: From gene to base editing},
	journal = {Med Res Rev},
	volume = {39},
	number = {2},
	year = {2019},
	month = {2019 03},
	pages = {665-683},
	abstract = {The system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated endonucleases (Cas) has been utilized for genome editing with great accuracy and high efficiency in generating gene knockout, knockin, and point mutations in eukaryotic genomes. However, traditional CRISPR/Cas9 technology introduces\&nbsp;double-stranded DNA breaks (DSBs) at a target locus as the first step to make gene corrections, which easily results in undesired mutations. Thus, it is necessary to develop new methods for correcting the unwanted mutations. In this review, we summarize the recent developments and a new approach to genome and base editing by using CRISPR/Cas9. This methodology renders a conversion of one target base into another, for example, C to T (or G to A), and A to G (or T to C) without producing DSBs, requiring a donor DNA template, or generating excessive insertions and deletions. Furthermore, CRISPR/Cas9-derived base editing also improves efficiency in repairing point mutations in the genome.},
	issn = {1098-1128},
	doi = {10.1002/med.21537},
	author = {Wu, Wenyi and Yang, Yanhui and Lei, Hetian}
}
@article {1351217,
	title = {Age-related macular degeneration and the incidence of cardiovascular disease: a systematic review and meta-analysis},
	journal = {PLoS One},
	volume = {9},
	number = {3},
	year = {2014},
	month = {2014},
	pages = {e89600},
	abstract = {IMPORTANCE: Research has indicated some shared pathogenic mechanisms between age-related macular degeneration (AMD) and cardiovascular disease (CVD). However, results from prior epidemiologic studies have been inconsistent as to whether AMD is predictive of future CVD risk. OBJECTIVE: To systematically review population-based cohort studies of the association between AMD and risk of total CVD and CVD subtypes, coronary heart disease (CHD) and stroke. DATA SOURCES: A systematic search of the PubMed and EMBASE databases and reference lists of key retrieved articles up to December 20, 2012 without language restriction. DATA EXTRACTION: Two reviewers independently extracted data on baseline AMD status, risk estimates of CVD and methods used to assess AMD and CVD. We pooled relative risks using random or fixed effects models as appropriate. RESULTS: Thirteen cohort studies (8 prospective and 5 retrospective studies) with a total of 1,593,390 participants with 155,500 CVD events (92,039 stroke and 62,737 CHD) were included in this meta-analysis. Among all studies, early AMD was associated with a 15\% (95\% CI, 1.08-1.22) increased risk of total CVD. The relative risk was similar but not significant for late AMD (RR, 1.17; 95\% CI, 0.98-1.40). In analyses restricted to the subset of prospective studies, the risk associated with early AMD did not appreciably change; however, there was a marked 66\% (95\% CI, 1.31-2.10) increased risk of CVD among those with late AMD. CONCLUSION: Whereas the results from all cohort studies suggest that both early and late AMD are predictive of a small increase in risk of future CVD, subgroup analyses limited to prospective studies demonstrate a markedly increased risk of CVD among people with late AMD. Retrospective studies using healthcare databases may have inherent methodological limitations that obscure such association. Additional prospective studies are needed to further elucidate the associations between AMD and specific CVD outcomes.},
	keywords = {Aged, Cardiovascular Diseases, Humans, Incidence, Macular Degeneration, Middle Aged, Prospective Studies, Retrospective Studies, Risk, Risk Factors},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0089600},
	author = {Wu, Juan and Uchino, Miki and Sastry, Srinivas M and Schaumberg, Debra A}
}
@article {1589768,
	title = {Impact of higher oxygen saturation levels on postnatal weight gain to predict retinopathy of prematurity},
	journal = {Acta Paediatr},
	volume = {110},
	number = {8},
	year = {2021},
	month = {2021 08},
	pages = {2348-2349},
	keywords = {Birth Weight, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Oxygen, Retinopathy of Prematurity, Risk Factors, Weight Gain},
	issn = {1651-2227},
	doi = {10.1111/apa.15868},
	author = {Wu, Carolyn and VanderVeen, Deborah K}
}
@article {369016,
	title = {Correlation of localized glaucomatous visual field defects and spectral domain optical coherence tomography retinal nerve fiber layer thinning using a modified structure-function map for OCT.},
	journal = {Eye (Lond)},
	volume = {29},
	number = {4},
	year = {2015},
	month = {2015 Apr},
	pages = {525-33},
	abstract = {PurposeTo study the correlation between glaucomatous visual field (VF) defects assessed by standard automated perimetry (SAP) and peripapillary retinal nerve fiber layer (RNFL) thinning measured by spectral domain optical coherence tomography (OCT) using a modified OCT-based peripapillary RNFL structure-function map.Patients and methodsPerimetric glaucoma patients and age-matched normal control subjects were recruited from a university hospital clinic. All eyes underwent testing with the Spectralis spectral domain OCT and SAP on the same day. An OCT-based correspondence map, which correlated VF areas with peripapillary RNFL sectors was created to evaluate the relationship between glaucomatous RNFL thinning and VF loss in six nerve fiber layer bundle areas. Correlations of RNFL thinning with corresponding VF defects were examined using Spearman rank-order correlations. To demonstrate the association between localized VF defects and RNFL thickness, the theoretical curves were made according to an established log-linear model. The measured RNFL thickness values and VF defects were presented in the same scatterplot for each sector.ResultsFifty-six glaucoma patients and 85 normal subjects were included in the study. Significant association between localized VF loss and RNFL thinning was found in corresponding areas. Data from the current study fit well with established log-linear models, which compare RNFL thickness values with VF defects.ConclusionAnalysis of RNFL thinning in eyes with localized glaucomatous VF defects showed good structure-function correlation in a new OCT-based structure-function correspondence map.},
	issn = {1476-5454},
	doi = {10.1038/eye.2014.317},
	author = {Wu, H and de Boer, J F and Chen, L and Chen, T. C.}
}
@article {1655706,
	title = {Xenogenic induction of adipose tissue and maintenance through pre- and post-conditioning using external volume expansion},
	journal = {Biomed Mater},
	volume = {17},
	number = {6},
	year = {2022},
	month = {2022 Oct 07},
	abstract = {External volume expansion (EVE) has been shown to improve fat graft survival. In this study, we investigated the xenogenic implantation of human allograft adipose matrix (AAM) in non-immunocompromised mice in combination with pre- and post-conditioning with EVE to assess long-term adipose tissue survival. Sixty-eight recipient sites in thirty-four eight-week-old wild type (C57BL/6J) mice were separated into four groups. Thirty-four sites received no conditioning and either a subcutaneous injection of 300 μl saline (n= 17; PBS group) or AAM (n= 17; AAM group). Thirty-four sites received pre-conditioning with EVE (Day -7-3 pre-grafting) and 300 μl of AAM. Seventeen of these sites received immediate post-conditioning (Day 1-5 post-grafting) and 17 delayed post-conditioning (Day 28-32 post-grafting). Tissue was harvested at week 12 for analysis. At 12 weeks, immediate and delayed post-conditioning enabled higher volume retention (p= 0.02 andp\&lt; 0.0001, respectively). Adipose Stem Cells were greater in the AAM+Del-EVE group compared to the AAM (p= 0.01). Microvessel density was lower in the AAM group compared to the AAM+Imm-EVE (p= 0.04) and AAM+Del-EVE group (p= 0.02). Macrophage infiltration was lower in the AAM+Imm-EVE (p= 0.002) and AAM+Del-EVE (p= 0.003) groups compared to the AAM group. PCR analysis and Western blotting identified a significantly higher expression of PPAR-γ, LPL and VEGF with delayed-conditioning. Pre- and post-conditioning, particularly delayed-post-conditioning, of the recipient site optimized the microenvironment allowing significant adipogenesis and survival of neo-adipose tissue through robust angiogenesis. This study supports that xenogenic transplantation of adipose matrix allows adipose tissue formation and survival with EVE as an adjuvant.},
	keywords = {Adipogenesis, Adipose Tissue, Animals, Humans, Mice, Mice, Inbred C57BL, Peroxisome Proliferator-Activated Receptors, Vascular Endothelial Growth Factor A},
	issn = {1748-605X},
	doi = {10.1088/1748-605X/ac934b},
	author = {Wu, Mengfan and Matar, Dany Y and Yu, Zhen and Karvar, Mehran and Chen, Ziyu and Ng, Brian and Knoedler, Samuel and Darwish, Oliver and Agarwal, Shailesh and Orgill, Dennis P and Panayi, Adriana C}
}
@article {1661821,
	title = {Racial Disparities Affecting Black Patients In Glaucoma Diagnosis And Management},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {1},
	year = {2023},
	month = {2023 Jan},
	pages = {65-75},
	abstract = {Black patients are more affected by glaucoma and suffer from more advanced disease. Diagnostic challenges among black patients with glaucoma include lower rates of diagnostic testing and thinner average central corneal thickness, the latter of which affects intraocular pressure measurement. Treatment challenges include poor follow-up, medication adherence, and trust in providers. Black patients undergoing trabeculectomy have higher rates of failure compared to white patients. Race is not a definitive factor affecting success for tube shunts, laser trabeculoplasty, cyclophotocoagulation, and micro-invasive glaucoma surgeries, but the body of evidence is limited by low inclusion of black patients in these studies. Future steps should include increased attention toward improving trust between patients and providers, improving access to care, and increased representation of black patients in glaucoma research to better understand factors affecting racial disparities in glaucoma management and outcomes in this population disproportionately affected by the disease.},
	keywords = {Black People, Glaucoma, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Laser Therapy, Trabeculectomy},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152702},
	author = {Wu, Annie M and Shen, Lucy Q}
}
@article {1664951,
	title = {Genome Editing of Pik3cd Impedes Abnormal Retinal Angiogenesis},
	journal = {Hum Gene Ther},
	volume = {34},
	number = {1-2},
	year = {2023},
	month = {2023 Jan},
	pages = {30-41},
	abstract = {Abnormal angiogenesis is associated with myriad human diseases, including proliferative diabetic retinopathy (PDR). Signaling transduction through phosphoinositide 3-kinases (PI3Ks) plays a critical role in angiogenesis. Herein, we showed that p110δ, the catalytic subunit of PI3Kδ, was highly expressed in pathological retinal vascular endothelial cells (ECs) in a mouse model of oxygen-induced retinopathy (OIR) and in fibrovascular membranes from patients with PDR. To explore novel intervention with PI3Kδ expression, we developed a recombinant dual adeno-associated viral (rAAV) system for delivering CRISPR/Cas9 in which Streptococcus pyogenes (Sp) Cas9 expression was driven by an endothelial specific promoter of the intercellular adhesion molecule 2 (pICAM2) to edit genomic Pik3cd, the gene encoding p110δ. We then demonstrated that infection of cultured mouse vascular ECs with the dual rAAV1s of rAAV1-pICAM2-SpCas9 and rAAV1-SpGuide targeting genomic Pik3cd resulted in 80\% DNA insertion/deletion in the locus of genomic Pik3cd and 70\% depletion of p110δ expression. Furthermore, we showed that in the mouse model of OIR editing retinal Pik3cd with the dual rAAV1s resulted in not only a significant decrease in p110δ expression, and Akt activation, but also a dramatic reduction in pathological retinal angiogenesis. These findings reveal that Pik3cd editing is a novel approach to treating abnormal retinal angiogenesis.},
	keywords = {Animals, Cells, Cultured, Class I Phosphatidylinositol 3-Kinases, Endothelial Cells, Gene Editing, Humans, Mice, Neovascularization, Pathologic, Retina, Retinal Diseases},
	issn = {1557-7422},
	doi = {10.1089/hum.2022.079},
	author = {Wu, Wenyi and Ma, Gaoen and Qi, Hui and Dong, Lijun and Chen, Fang and Wang, Yun and Mao, Xingxing and Guo, Xiaoqing and Cui, Jing and Matsubara, Joanne Aiko and Vanhaesebroeck, Bart and Yan, Xiaohe and Zhao, Guoming and Zhang, Shaochong and Lei, Hetian}
}
@article {837011,
	title = {Signaling Networks of Retinal Ganglion Cell Formation and the Potential Application of Stem Cell-Based Therapy in Retinal Degenerative Diseases.},
	journal = {Hum Gene Ther},
	volume = {27},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {609-620},
	abstract = {Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons. Here, recent findings concerning the intrinsic and extrinsic factors that regulate retinal progenitor cell maintenance and differentiation are summarized, especially transcriptional factors and extrinsic signals. Understanding these mechanisms is indispensable because they have potential clinical applications, chiefly the generation of specific retinal cells such as retinal ganglion cells to treat glaucoma and other optic neuropathy diseases.},
	issn = {1557-7422},
	doi = {10.1089/hum.2016.083},
	author = {Wu, Nan and Wang, Yi and Yang, Lanbo and Cho, Kin-Sang}
}
@article {1430545,
	title = {Initiation of fibrosis in the integrin Αvβ6 knockout mice},
	journal = {Exp Eye Res},
	volume = {180},
	year = {2019},
	month = {2019 Mar},
	pages = {23-28},
	abstract = {We previously demonstrated that β6 knockout mice showed impaired wound repair in corneal debridement and keratectomy wounds. In the current investigation, we continued our examination of integrin αvβ6 in order to determine if it was required for the initiation of wound healing in a corneal wound model that normally heals in a fibrotic manner. A full-thickness corneal incision was made in C57BL/6 J wild type (WT) and C57BL/6-Itgb6 KO (β6) mice. The mice were observed at 3, 7, 14, and 28 days post-incision. The morphology of corneal restoration was observed in tissue sections stained with hemotoxilin and eosin (H\&amp;E). In addition, indirect-immunofluorescence (IF) was performed on sections and/or whole mounts to evaluate the immunolocalization of α-smooth muscle actin (SMA) and thrombospondin-1 (TSP-1). H\&amp;E staining revealed that the corneas in β6 mice healed slower than those in WT mice, with an obvious delay in the restoration of the stromal matrix and epithelium. In sections at 3 and 7 days, SMA and TSP-1 were greatly reduced in the β6 mice as compared to WT, but peaked at 28 days after incision. Whole mount SMA IF results were consistent with those from sections. Therefore, the initiation of fibrosis was inhibited by the lack of αvβ6; however, there appeared to be an alternate mechanism that initiated fibrosis 7-14 days later. Localization of TSP-1 correlated with expression of SMA whether wound healing was delayed or initiated immediately after wounding.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2018.11.027},
	author = {Wu, Wenjing and Hutcheon, Audrey E K and Sriram, Sriniwas and Tran, Jennifer A and Zieske, James D}
}
@article {1661604,
	title = {Corrigendum: Regional homogeneity in patients with mild cognitive impairment: A resting-state functional magnetic resonance imaging study},
	journal = {Front Aging Neurosci},
	volume = {14},
	year = {2022},
	month = {2022},
	pages = {1098983},
	abstract = {[This corrects the article DOI: 10.3389/fnagi.2022.877281.].},
	issn = {1663-4365},
	doi = {10.3389/fnagi.2022.1098983},
	author = {Wu, Yu-Qian and Wang, Yi-Ning and Zhang, Li-Juan and Liu, Li-Qi and Pan, Yi-Cong and Su, Ting and Liao, Xu-Lin and Shu, Hui-Ye and Kang, Min and Ying, Ping and Xu, San-Hua and Shao, Yi}
}
@article {1364572,
	title = {Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity},
	journal = {Arch Ophthalmol},
	volume = {130},
	number = {8},
	year = {2012},
	month = {2012 Aug},
	pages = {992-9},
	abstract = {OBJECTIVE: To assess WINROP (https://winrop.com), an algorithm using postnatal weight measurements, as a tool for the prediction of retinopathy of prematurity (ROP) in a large geographically and racially diverse study population. METHODS: WINROP analysis was performed retrospectively on conventionally at-risk infants from 10 neonatal intensive careunits.Weight measurements were entered into WINROP, which signals an alarm for an abnormal weight gain rate. Infants were classified into categories of no alarm (unlikely to develop type 1ROP)and alarm (at risk for developing type 1ROP).Use of WINROP requires that an infant has (1) gestational age less than 32 weeks at birth, (2) weekly weight measurements,(3) physiologic weight gain,and(4)absence of other pathologic retinal vascular disease. RESULTS: A total of 1706 infants with a median gestational age of 28 weeks (range, 22-31 weeks) and median birth weight of 1016 g (range, 378-2240 g) were included in the study analysis. An alarm occurred in 1101 infants (64.5\%), with a median time from birth to alarm of 3 weeks (range, 0-12 weeks) and from alarm to treatment of 8 weeks (range, 1 day to 22 weeks). The sensitivity of WINROP was 98.6\% and the negative predictive value was 99.7\%. Two infants with type 1 ROP requiring treatment after 40 weeks{\textquoteright} postmenstrual age did not receive an alarm. CONCLUSION: The WINROP system is a useful adjunct for ROP screening that identifies high-risk infants early to optimize care and potentially reduce the overall number of diagnostic ROP examinations.},
	keywords = {Algorithms, Birth Weight, False Positive Reactions, Female, Gestational Age, Humans, Infant, Newborn, Infant, Very Low Birth Weight, Intensive Care Units, Neonatal, Male, Predictive Value of Tests, Retinal Neovascularization, Retinal Vessels, Retinopathy of Prematurity, Retrospective Studies, Sensitivity and Specificity, Weight Gain},
	issn = {1538-3601},
	doi = {10.1001/archophthalmol.2012.243},
	author = {Wu, Carolyn and L{\"o}fqvist, Chatarina and Smith, Lois E H and VanderVeen, Deborah K and Hellstr{\"o}m, Ann and WINROP Consortium}
}
@article {1642011,
	title = {Human Amniotic Membrane Promotes Angiogenesis in an Oxidative Stress Chronic Diabetic Murine Wound Model},
	journal = {Adv Wound Care (New Rochelle)},
	volume = {12},
	number = {6},
	year = {2023},
	month = {2023 Jun},
	pages = {301-315},
	abstract = {Objective: The development of animal models, which adequately replicate the pathophysiology of chronic wounds, has been challenging. In this study, we utilized an oxidative stress (OS) murine model, which was previously developed by our group, to study the effect of a human amniotic membrane (AM) on chronic wound healing. Approach: Forty-five diabetic (genetically obese leptin receptor-deficient mice [db/db]) mice were separated into three groups. Thirty mice received an OS regimen and a 1 - {\texttimes} 1 cm2 full-thickness excisional dorsal wound. The wounds were either covered with AM and occlusive dressing (db/dbOS-AM) or occlusive dressing only (db/dbOS). Fifteen mice did not receive the OS regimen, and were covered with AM and occlusive dressing (db/db-AM). The wounds were photographed, and tissue was harvested at various time points. Results: Vascular density was higher in the AM-treated groups (db/dbOS-AM: 34 {\textpm} 12; db/db-AM: 37 {\textpm} 14; vs. db/dbOS: 19 {\textpm} 9 cluster of differentiation 31 [CD31+]/high power field [HPF] photograph; p = 0.04 and p = 0.003). Vessel maturity was lowest in the db/dbOS group (21\% {\textpm} 4\%; vs. db/dbOS-AM: 38\% {\textpm} 10\%, p = 0.004; db/db-AM: 40\% {\textpm} 11\%, p = 0.0005). Leukocyte infiltration was higher in the AM groups (db/dbOS-AM: 15 {\textpm} 4; db/db-AM: 16 {\textpm} 4 vs. db/dbOS: 8 {\textpm} 3 lymphocyte common antigen [CD45+]/HPF; p = 0.005 and p = 0.06). AM upregulated various proangiogenic factors, including vascular endothelial growth factor (VEGF), and downregulated genes involved in chronicity, such as osteopontin, as visualized through proteome analysis and western blotting. Cell death was lower in the AM groups (db/dbOS-AM: 28 {\textpm} 10, db/db-AM: 7 {\textpm} 5 vs. db/dbOS: 17\% {\textpm} 9\% Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling [TUNEL+]; p = 0.03 and p \&lt; 0.0001). Innovation: This study offers new insight on the mechanisms of action of human AM in chronic wound healing. Conclusion: AM treatment promoted healing in mice with complex chronic wounds. The AM stimulated angiogenesis through upregulation of proangiogenic factors, improving the wound milieu by increasing leukocyte and growth factor delivery and decreasing cell death.},
	keywords = {Amnion, Animals, Diabetes Mellitus, Humans, Mice, Vascular Endothelial Growth Factor A, Wound Healing},
	issn = {2162-1918},
	doi = {10.1089/wound.2022.0005},
	author = {Wu, Mengfan and Yu, Zhen and Matar, Dany Y and Karvar, Mehran and Chen, Ziyu and Ng, Brian and Aoki, Shimpo and Haug, Valentin and Orgill, Dennis P and Panayi, Adriana C}
}
@article {1483609,
	title = {PI3Kδ as a Novel Therapeutic Target in Pathological Angiogenesis},
	journal = {Diabetes},
	volume = {69},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {736-748},
	abstract = {Diabetic retinopathy is the most common microvascular complication of diabetes, and in the advanced diabetic retinopathy appear vitreal fibrovascular membranes that consist of a variety of cells, including vascular endothelial cells (ECs). New therapeutic approaches for this diabetic complication are urgently needed. Here, we report that in cultured human retinal microvascular ECs, high glucose induced expression of p110δ, which was also expressed in ECs of fibrovascular membranes from patients with diabetes. This catalytic subunit of a receptor-regulated PI3K isoform δ is known to be highly enriched in leukocytes. Using genetic and pharmacological approaches, we show that p110δ activity in cultured ECs controls Akt activation, cell proliferation, migration, and tube formation induced by vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth factor. Using a mouse model of oxygen-induced retinopathy, p110δ inactivation was found to attenuate pathological retinal angiogenesis. p110δ inhibitors have been approved for use in human B-cell malignancies. Our data suggest that antagonizing p110δ constitutes a previously unappreciated therapeutic opportunity for diabetic retinopathy.},
	issn = {1939-327X},
	doi = {10.2337/db19-0713},
	author = {Wu, Wenyi and Zhou, Guohong and Han, Haote and Huang, Xionggao and Jiang, Heng and Mukai, Shizuo and Kazlauskas, Andrius and Cui, Jing and Matsubara, Joanne Aiko and Vanhaesebroeck, Bart and Xia, Xiaobo and Wang, Jiantao and Lei, Hetian}
}
@article {1629456,
	title = {Treatment of Aggressive Retinal Astrocytic Hamartoma with Oral Mechanistic Target of Rapamycin Inhibition},
	journal = {Ophthalmol Retina},
	volume = {6},
	number = {5},
	year = {2022},
	month = {2022 May},
	pages = {411-420},
	abstract = {PURPOSE: To describe the clinical course and outcomes of aggressive retinal astrocytic hamartoma (RAH) treated with oral mechanistic target of rapamycin inhibitors (mTORis). DESIGN: A retrospective clinical case series. PARTICIPANTS: Five patients with genetically confirmed tuberous sclerosis complex and visually significant RAH due to tumor growth or exudation. METHODS: In this retrospective clinical case series, a review of electronic medical records was performed to determine baseline and follow-up ophthalmic examination characteristics, along with ancillary imaging findings, in patients receiving off-label treatment with either oral sirolimus or everolimus for symptomatic RAH. MAIN OUTCOME MEASURES: Visual acuity, change in tumor size, degree of exudation, and adverse effects of the mTORis were evaluated. RESULTS: The 5 patients in this series ranged in age from 8 months to 54 years. Four were treated with sirolimus, and 1 received everolimus. In all the cases, the tumor height was stable or decreased after the treatment (median follow-up duration, 39 months; range, 11-73 months). Exudation improved after the treatment in all the cases. In an 8-month-old infant, frequent upper respiratory tract infections prompted the cessation of treatment. In 1 patient, the mTORi was temporarily withheld because of elevated liver enzyme levels. No other significant adverse effects were noted. CONCLUSIONS: Sirolimus and everolimus should be considered in the management of vision-threatening RAH, particularly in the setting of exudative and rapidly growing tumors. Four of the 5 patients in this series tolerated the oral mTORi and continued with the therapy. There were no serious complications.},
	keywords = {Everolimus, Hamartoma, Humans, Infant, Retinal Diseases, Retrospective Studies, Sirolimus},
	issn = {2468-6530},
	doi = {10.1016/j.oret.2022.01.003},
	author = {Wu, Frances and McGarrey, Mark P and Geenen, Kennedy R and Skalet, Alison H and Guillot, Florian H and Wilson, Jenny L and Shah, Ankoor S and Gonzalez, Efren and Thiele, Elizabeth A and Kim, Ivana K and Aronow, Mary E}
}
@article {1351215,
	title = {Good visual outcome after repair of a very large macular hole with neurosensory retinal operculum},
	journal = {Retin Cases Brief Rep},
	volume = {8},
	number = {2},
	year = {2014},
	month = {2014 Spring},
	pages = {138-40},
	abstract = {PURPOSE: To describe a favorable outcome after the surgical repair of a very large macular hole with a neurosensory operculum. METHODS: Case report. A 42-year-old man with a history of decreased vision for 3 months was found to have vision of 20/400, a very large macular hole (1159 μm in diameter), and an operculum suspended on the posterior hyaloid above the hole. RESULTS: Vitrectomy and internal limiting membrane peel were performed. The operculum was processed for histology and found to contain neurons and glial cells. Fourteen months later, the patient{\textquoteright}s vision improved to 20/60. CONCLUSION: Very large macular holes have traditionally been considered to have a poor prognosis. Here, we demonstrate that such large holes can be repaired with good visual outcome, even in the setting of an operculum consisting of avulsed neural retina.},
	keywords = {Adult, Humans, Male, Retinal Neurons, Retinal Perforations, Treatment Outcome, Vitrectomy},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000025},
	author = {Wu, David M and Fawzi, Amani A and Recasens, Marta A and Bertoni, Bruno and Chopra, Vikas and Rao, Narsing A and Eliott, Dean}
}
@article {1549030,
	title = {Normal vitreous promotes angiogenesis via activation of Axl},
	journal = {FASEB J},
	volume = {35},
	number = {1},
	year = {2021},
	month = {2021 Jan},
	pages = {e21152},
	abstract = {Vitreous has been reported to prevent tumor angiogenesis, but our previous findings indicate that vitreous activate the signaling pathway of phosphoinositide 3-kinase (PI3K)/Akt, which plays a critical role in angiogenesis. The goal of this research is to determine which role of vitreous plays in angiogenesis-related cellular responses in vitro. We found that in human retinal microvascular endothelial cells (HRECs) vitreous activates a number of receptor tyrosine kinases including Anexelekto (Axl), which plays an important role in angiogenesis. Subsequently, we discovered that depletion of Axl using CRISPR/Cas9 and an Axl-specific inhibitor R428 suppress vitreous-induced Akt activation and cell proliferation, migration, and tuber formation of HRECs. Therefore, this line of research not only demonstrate that vitreous promotes angiogenesis in vitro, but also reveal that Axl is one of receptor tyrosine kinases to mediate vitreous-induced angiogenesis in vitro, thereby providing a molecular basis for removal of vitreous as cleanly as possible when vitrectomy is performed in treating patients with proliferative diabetic retinopathy.},
	issn = {1530-6860},
	doi = {10.1096/fj.201903105R},
	author = {Wu, Wenyi and Xia, Xiaobo and Tang, Luosheng and Yao, Fei and Xu, Huizuo and Lei, Hetian}
}
@article {1043301,
	title = {The association of maternal factors with epibulbar dermoid of newborn: a retrospective, matched case-control study},
	journal = {Eye (Lond)},
	volume = {31},
	number = {7},
	year = {2017},
	month = {2017 Jul},
	pages = {1099-1105},
	abstract = {PurposeTo determine the association of maternal factors and exposure during pregnancy with the incidence in newborns of epibulbar dermoid (ED), a congenital ocular surface benign tumor.Patients and methodsThis is a retrospective, paired case-control study in which 121 children with ED (case group) and 121 children without ED (control group) were recruited. Questionnaire-based interviews with mothers of participants were performed and maternal medical records during pregnancy were reviewed. The questionnaire investigated basic information, personal history, environmental exposure, exposure to maternal diseases, symptoms and corresponding medical treatments during pregnancy, and parental socioeconomic status. The case and control participants were matched for sex, birth weight, gestational age, and parental socioeconomic status level. Univariate and multivariate logistic regression analyses were conducted with ED as the main outcome variable.ResultsFactors significantly associated with ED were: history of maternal inevitable miscarriage (odds ratio (OR), 2.59; 95\% confidence intervals (CI), 1.13-5.90), common cold in the first trimester (OR, 3.94; CI, 1.74-8.93), and paternal smoke exposure \&gt;half a pack per day during pregnancy (OR, 4.81; CI, 1.74-13.28).ConclusionHistory of maternal miscarriage, common cold exposure in the first trimester, and paternal smoking (\&gt;half a pack per day) during pregnancy could result in significant risk factors for ED of newborns. These data also imply that paternal smoking delivers nicotine to maternal respiratory system and uterine microenvironment that may both affect microvascular development and predispose the fetus to future ED.},
	issn = {1476-5454},
	doi = {10.1038/eye.2017.40},
	author = {Wu, S. and Fan, Y and Wu, D and Hong, J. and Xu, J}
}
@article {1761991,
	title = {Steroid Response Following Dropless Cataract Surgery Using Subconjunctival Triamcinolone},
	journal = {Clin Ophthalmol},
	volume = {17},
	year = {2023},
	month = {2023},
	pages = {2803-2814},
	abstract = {PURPOSE: To assess the rates of postoperative steroid response following dropless cataract surgery using a subconjunctival depot of triamcinolone versus conventional cataract surgery using topical prednisolone. PATIENTS AND METHODS: We reviewed consecutive cataract surgery cases performed by a single surgeon to determine the likelihood of steroid response, defined as intraocular pressure (IOP) 50\% above baseline or IOP \&gt; 24 mmHg postoperatively, excluding the first 72 hours. Logistic regression models were performed including baseline characteristics as exposures in the model and steroid response as the outcome. Main outcome measures were the proportion of eyes developing steroid response, risk factors for developing steroid response, and duration of steroid response. RESULTS: Of the 150 dropless and 218 conventional cases, 26 eyes developed steroid response (15 dropless and 11 conventional cases [10\% vs 5\%, P=0.096]). Risk factors for steroid response included dropless surgery (OR=2.43, 95\% CI=1.03-6.02], P=0.046) and prior diagnosis of glaucoma (OR=7.18, 95\% CI=2.66-19.22], P\&lt;0.001). Baseline IOP, age, sex, race, and axial length did not increase risk for steroid response. Of the eyes with steroid response, more dropless cases had an IOP elevation >=30 days (9/15 eyes vs 1/11 eyes; P=0.008), including one patient with refractory IOP elevation in the dropless group who required urgent bilateral trabeculectomy for IOP control. CONCLUSION: Dropless cataract surgery increases the risk of prolonged steroid response postoperatively. Patients with glaucoma have an increased risk of steroid response and may not be good candidates for dropless cataract surgery with subconjunctival triamcinolone.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S426200},
	author = {Wu, Annie M and Pitts, Kristen M and Pineda, Roberto and Chen, Sherleen H and Wang, Mengyu and Johnson, Grace and Shen, Lucy Q and Margeta, Milica A}
}
@article {560166,
	title = {Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up.},
	journal = {JAMA Ophthalmol},
	year = {2015},
	month = {2015 Oct 8},
	pages = {1-10},
	abstract = {Importance: Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated. Objective: To investigate the associations between intakes of carotenoids and AMD. Design, Setting, and Participants: Prospective cohort study, with cohorts from the Nurses{\textquoteright} Health Study and the Health Professionals Follow-up Study in the United States. A total of 63 443 women and 38 603 men were followed up, from 1984 until May 31, 2010, in the Nurses{\textquoteright} Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline. Main Outcomes and Measures: Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined. Results: We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40\% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95\% CI, 0.48-0.73; P for trend \&lt; .001). Predicted plasma carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25\% to 35\% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95\% CI, 0.53-0.80; P for trend \&lt; .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD. Conclusions and Relevance: Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.3590},
	author = {Wu, Juan and Cho, Eunyoung and Willett, Walter C and Sastry, Srinivas M and Schaumberg, Debra A}
}
@article {1655711,
	title = {Continuous NPWT Regulates Fibrosis in Murine Diabetic Wound Healing},
	journal = {Pharmaceutics},
	volume = {14},
	number = {10},
	year = {2022},
	month = {2022 Oct 06},
	abstract = {Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (p = 0.04) but decreased En1 (p = 0.0001) and CD26 (p \&amp;lt; 0.0001). The pro-fibrotic factors Vimentin (p = 0.04), α-SMA (p = 0.04) and HSP47 (p = 0.0008) were decreased with NPWT. Fibronectin was higher (p = 0.01) and collagen deposition lower in the NPWT group (p = 0.02). NPWT increased cellular proliferation (p = 0.002) and decreased apoptosis (p = 0.03). Western blotting demonstrated increased YAP (p = 0.02) and RhoA (p = 0.03) and decreased Caspase-3 (p = 0.03) with NPWT. NPWT uncouples YAP from EPF activation, through downregulation of Caspace-3, a pro-apoptotic factor linked to keloid formation. Mechanotransduction decreases multiple pro-fibrotic factors. Through this multifactorial process, NPWT significantly decreases fibrosis and offers promising potential as a mode to improve scar appearance.},
	issn = {1999-4923},
	doi = {10.3390/pharmaceutics14102125},
	author = {Wu, Mengfan and Matar, Dany Y and Yu, Zhen and Chen, Ziyu and Knoedler, Samuel and Ng, Brian and Darwish, Oliver A and Sohrabi, Sadaf and Friedman, Leigh and Haug, Valentin and Murphy, George F and Rinkevich, Yuval and Orgill, Dennis P and Panayi, Adriana C}
}
@article {1109891,
	title = {Application of CRISPR-Cas9 in eye disease},
	journal = {Exp Eye Res},
	volume = {161},
	year = {2017},
	month = {2017 Aug},
	pages = {116-123},
	abstract = {The system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease (Cas)9 is an effective instrument for revising the genome with great accuracy. This system has been widely employed to generate mutants in genomes from plants to human cells. Rapid improvements in Cas9 specificity in eukaryotic cells have opened great potential for the use of this technology as a therapeutic. Herein, we summarize the recent advancements of CRISPR-Cas9 use in research on human cells and animal models, and outline a basic and clinical pipeline for CRISPR-Cas9-based treatments of genetic eye diseases.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2017.06.007},
	author = {Wu, Wenyi and Tang, Luosheng and D{\textquoteright}Amore, Patricia A and Lei, Hetian}
}
@article {1364573,
	title = {Diagnostic capability of spectral-domain optical coherence tomography for glaucoma},
	journal = {Am J Ophthalmol},
	volume = {153},
	number = {5},
	year = {2012},
	month = {2012 May},
	pages = {815-826.e2},
	abstract = {PURPOSE: To determine the diagnostic capability of spectral-domain optical coherence tomography in glaucoma patients with visual field defects. DESIGN: Prospective, cross-sectional study. METHODS: SETTINGS: Participants were recruited from a university hospital clinic. STUDY POPULATION: One eye of 85 normal subjects and 61 glaucoma patients with average visual field mean deviation of -9.61 {\textpm} 8.76 dB was selected randomly for the study. A subgroup of the glaucoma patients with early visual field defects was calculated separately. OBSERVATION PROCEDURES: Spectralis optical coherence tomography (Heidelberg Engineering, Inc) circular scans were performed to obtain peripapillary retinal nerve fiber layer (RNFL) thicknesses. The RNFL diagnostic parameters based on the normative database were used alone or in combination for identifying glaucomatous RNFL thinning. MAIN OUTCOME MEASURES: To evaluate diagnostic performance, calculations included areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: Overall RNFL thickness had the highest area under the receiver operating characteristic curve values: 0.952 for all patients and 0.895 for the early glaucoma subgroup. For all patients, the highest sensitivity (98.4\%; 95\% confidence interval, 96.3\% to 100\%) was achieved by using 2 criteria: >= 1 RNFL sectors being abnormal at the \&lt; 5\% level and overall classification of borderline or outside normal limits, with specificities of 88.9\% (95\% confidence interval, 84.0\% to 94.0\%) and 87.1\% (95\% confidence interval, 81.6\% to 92.5\%), respectively, for these 2 criteria. CONCLUSIONS: Statistical parameters for evaluating the diagnostic performance of the Spectralis spectral-domain optical coherence tomography were good for early perimetric glaucoma and were excellent for moderately advanced perimetric glaucoma.},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, False Positive Reactions, Female, Glaucoma, Humans, Intraocular Pressure, Likelihood Functions, Male, Middle Aged, Nerve Fibers, Optic Disk, Optic Nerve Diseases, Predictive Value of Tests, Prospective Studies, Reproducibility of Results, Retinal Ganglion Cells, ROC Curve, Sensitivity and Specificity, Tomography, Optical Coherence, Vision Disorders, Visual Field Tests, Visual Fields},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2011.09.032},
	author = {Wu, Huijuan and de Boer, Johannes F and Chen, Teresa C}
}
@article {961736,
	title = {Medically uncontrolled conjunctival pyogenic granulomas: correlation between clinical characteristics and histological findings.},
	journal = {Oncotarget},
	volume = {8},
	number = {2},
	year = {2017},
	pages = {2020-2024},
	abstract = {BACKGROUND: Conjunctival pyogenic granulomas are commonly seen after ocular surgeries or at an ocular wound site. The aim of this study is to describe a novel histological classification for medically uncontrolled conjunctival pyogenic granulomas (MUCPG), and to explore whether the diversity in clinical features correlates to different histological subtypes of MUCPG. METHODS: This is an observational cross-section case series. We reviewed 46 consecutive patients with conjunctival pyogenic granulomas who did not respond to topical corticosteroids and underwent surgical excision from January 1, 2006 through December 31, 2015. Clinical features and histological findings were presented and analyzed. RESULTS: Ocular surgery, accidental injury, and chalazion were the main predisposing causes of MUCPG. The lesions tended to occur unilaterally on the bulbar conjunctiva. Forty patients (87\%) presented an enrichment of inflammatory cells and proliferated capillaries in their pathological sections (inflammatory pattern). Six patients (13\%) showed relatively few inflammatory cells and capillaries within fibrous stroma (fibrous pattern). Patients with the inflammatory pattern were older (p = 0.025) and tended to be located in bulbar conjunctiva (p = 0.002). The predisposing causes were also different between two histological subtypes (p = 0.007). CONCLUSIONS: We found the correlation between clinical presentation and histological subtypes in patients with MUCPG, indicating this disease may need a new classification scheme.},
	issn = {1949-2553},
	doi = {10.18632/oncotarget.13961},
	author = {Wu, Dan and Qian, Tingting and Nakao, Takeshi and Xu, Jianjiang and Liu, Zuguo and Sun, Xinghuai and Chu, Yiwei and Hong, Jiaxu}
}
@article {1351216,
	title = {Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: the National Health and Nutrition Examination Survey 2005 to 2008},
	journal = {Environ Res},
	volume = {133},
	year = {2014},
	month = {2014 Aug},
	pages = {178-84},
	abstract = {Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005-2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6\% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95\% CI, 1.02-2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95\% CI, 0.91-2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95\% CI, 1.37-8.01 for levels above versus below the median among NHW; OR,1.45; 95\% CI, 0.40-5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn.},
	keywords = {Aged, Cadmium, Cross-Sectional Studies, Environmental Exposure, Female, Humans, Lead, Macular Degeneration, Male, Middle Aged, Nutrition Surveys, United States},
	issn = {1096-0953},
	doi = {10.1016/j.envres.2014.05.023},
	author = {Wu, Erin W and Schaumberg, Debra A and Park, Sung Kyun}
}
@article {1580482,
	title = {OCT Angiography for the Diagnosis of Glaucoma: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {128},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {1222-1235},
	abstract = {PURPOSE: To review the current published literature on the use of OCT angiography (OCTA) to help detect changes associated with the diagnosis of primary open-angle glaucoma. METHODS: Searches of the peer-reviewed literature were conducted in March 2018, June 2018, April 2019, December 2019, and June 2020 in the PubMed and Cochrane Library databases. Abstracts of 459 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 75 articles were selected and the panel methodologist rated them for strength of evidence. Three articles were rated level I and 57 articles were rated level II. The 15 level III articles were excluded. RESULTS: OCT angiography can detect decreased capillary vessel density within the peripapillary nerve fiber layer (level II) and macula (level I and II) in patients with suspected glaucoma, preperimetric glaucoma, and perimetric glaucoma. The degree of vessel density loss correlates significantly with glaucoma severity both overall and topographically (level II) as well as longitudinally (level I). For differentiating glaucomatous from healthy eyes, some studies found that peripapillary and macular vessel density measurements by OCTA show a diagnostic ability (area under the receiver operating characteristic curve) that is comparable with structural OCT retinal nerve fiber and ganglion cell thickness measurements, whereas other studies found that structural OCT measurements perform better. Choroidal or deep-layer microvasculature dropout as measured by OCTA is also associated with glaucoma damage (level I and II). Lower peripapillary and macular vessel density and choroidal microvasculature dropout are associated with faster rates of disease progression (level I and II). CONCLUSIONS: Vessel density loss associated with glaucoma can be detected by OCTA. Peripapillary, macular, and choroidal vessel density parameters may complement visual field and structural OCT measurements in the diagnosis of glaucoma.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.12.027},
	author = {WuDunn, Darrell and Takusagawa, Hana L and Sit, Arthur J and Rosdahl, Jullia A and Radhakrishnan, Sunita and Hoguet, Ambika and Han, Ying and Chen, Teresa C}
}
@article {1789186,
	title = {Central Visual Field Testing in Early Glaucoma: A Report by the American Academy of Ophthalmology},
	journal = {Ophthalmology},
	volume = {131},
	number = {2},
	year = {2024},
	month = {2024 Feb},
	pages = {240-248},
	abstract = {PURPOSE: To evaluate the current published literature on the utility of the 10-2 visual field (VF) testing strategy for the evaluation and management of early glaucoma, defined here as mean deviation (MD) better than -6 decibels (dB). METHODS: A search of the peer-reviewed literature was last conducted in June 2023 in the PubMed database. Abstracts of 986 articles were examined to exclude reviews and non-English-language articles. After inclusion and exclusion criteria were applied, 26 articles were selected, and the panel methodologist rated them for strength of evidence. Thirteen articles were rated level I, and 8 articles were rated level II. The 5 level III articles were excluded. Data from the 21 included articles were abstracted and reviewed. RESULTS: The central 12 locations on the 24-2 VF test grid lie within the central 10 degrees covered by the 10-2 VF test. In early glaucoma, defects detected within the central 10 degrees generally agree between the 2 tests. Defects within the central 10 degrees of the 24-2 VF test can predict defects on the 10-2 VF test, although the 24-2 may miss defects detected on the 10-2 VF test. In addition, results from the 10-2 VF test show better association with findings from OCT scans of the macular ganglion cell complex. Modifications of the 24-2 test that include extra test locations within the central 10 degrees improve detection of central defects found on 10-2 VF testing. CONCLUSIONS: Evidence to date does not support routine testing using 10-2 VF for patients with early glaucoma. However, early 10-2 VF testing may provide sufficient additional information for some patients, particularly those with a repeatable\&nbsp;defect within the central 12 locations of the standard 24-2 VF test or who have inner retinal layer thinning on OCT scans of the macula. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
	keywords = {Glaucoma, Humans, Intraocular Pressure, Ophthalmology, Retinal Ganglion Cells, Scotoma, Tomography, Optical Coherence, United States, Visual Field Tests, Visual Fields},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.10.008},
	author = {WuDunn, Darrell and Takusagawa, Hana L and Rosdahl, Jullia A and Sit, Arthur J and Chopra, Vikas and Ou, Yvonne and Richter, Grace M and Knight, O{\textquoteright}Rese J and Sol{\'a}-Del Valle, David and Kim, Stephen J}
}
@article {742336,
	title = {Impact of Antibiotic Use on the Evolution of Enterococcus faecium.},
	journal = {J Infect Dis},
	volume = {213},
	number = {12},
	year = {2016},
	month = {2016 Jun 15},
	pages = {1862-5},
	issn = {1537-6613},
	doi = {10.1093/infdis/jiv598},
	author = {Wurster, Jenna I and Saavedra, Jos{\'e} T and Gilmore, Michael S}
}
@article {1402591,
	title = {Staphylococcus aureus from ocular and otolaryngology infections are frequently resistant to clinically important antibiotics and are associated with lineages of community and hospital origins},
	journal = {PLoS One},
	volume = {13},
	number = {12},
	year = {2018},
	month = {2018},
	pages = {e0208518},
	abstract = {Staphylococcus aureus is an important human pathogen that causes serious antibiotic-resistant infections. Its population structure is marked by the appearance and dissemination of successful lineages across different settings. To begin understanding the population structure of S. aureus causing ocular and otolaryngology infections, we characterized 262 isolates by antimicrobial sensitivity testing and multilocus sequence typing (MLST). Methicillin-resistant S. aureus were subjected to SCCmec typing and Panton-Valentine leukocidin (PVL) screening. Although we detected a high level of genetic diversity among methicillin-sensitive (MSSA) isolates, (63 sequence types-STs), the population was dominated by five lineages: ST30, ST5, ST8, ST15 and ST97. Resistance to penicillin, erythromycin and clindamycin was common among the major MSSA lineages, with fluctuations markedly impacted by genetic background. Isolates belonging to the predominant lineage, ST30, displayed high rates of resistance to penicillin (100\%), erythromycin (71\%), and clindamycin (63\%). Overall, 21\% of the isolates were methicillin-resistant (MRSA), with an apparent enrichment among otitis and orbital cellulitis isolates (\&gt;40\%). MRSA isolates belonged to 14 STs grouped in 5 clonal complexes (CC), however, CC5 (56.1\%) and CC8 (38.6\%) dominated the population. Most CC5 strains were SCCmec type II, and resembled the hospital-adapted USA100 clone. CC8 strains were SCCmec type IV, and 86\% were positive for the PVL toxin, common features of the community-acquired clone USA300. CC5 strains harboring a SCCmec type IV, typical for the USA800 clone, comprised 15.5\% of the population. USA100 strains were highly resistant to clindamycin, erythromycin and levofloxacin (100\%), while USA300 strains were frequently resistant to erythromycin (89\%) but displayed lower rates of resistance to levofloxacin (39\%) and clindamycin (17\%). Our data demonstrate that the ocular and otolaryngology S. aureus populations are composed of strains that are commonly resistant to clinically relevant antibiotics, and are associated with the major epidemic clonal complexes of both community and hospital origins.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0208518},
	author = {Wurster, Jenna I and Bispo, Paulo J M and Van Tyne, Daria and Cadorette, James J and Boody, Rick and Gilmore, Michael S}
}
@article {1629471,
	title = {Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials},
	journal = {Lancet},
	volume = {399},
	number = {10326},
	year = {2022},
	month = {2022 02 19},
	pages = {741-755},
	abstract = {BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6{\textperiodcentered}0 mg every 8 weeks, faricimab 6{\textperiodcentered}0 mg per personalised treatment interval (PTI), or aflibercept 2{\textperiodcentered}0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10{\textperiodcentered}7 ETDRS letters [97{\textperiodcentered}52\% CI 9{\textperiodcentered}4 to 12{\textperiodcentered}0] vs 10{\textperiodcentered}9 ETDRS letters [9{\textperiodcentered}6 to 12{\textperiodcentered}2], difference -0{\textperiodcentered}2 ETDRS letters [-2{\textperiodcentered}0 to 1{\textperiodcentered}6]; RHINE 11{\textperiodcentered}8 ETDRS letters [10{\textperiodcentered}6 to 13{\textperiodcentered}0] vs 10{\textperiodcentered}3 ETDRS letters [9{\textperiodcentered}1 to 11{\textperiodcentered}4] letters, difference 1{\textperiodcentered}5 ETDRS letters [-0{\textperiodcentered}1 to 3{\textperiodcentered}2]) and faricimab PTI (YOSEMITE 11{\textperiodcentered}6 ETDRS letters [10{\textperiodcentered}3 to 12{\textperiodcentered}9], difference 0{\textperiodcentered}7 ETDRS letters [-1{\textperiodcentered}1 to 2{\textperiodcentered}5]; RHINE 10{\textperiodcentered}8 ETDRS letters [9{\textperiodcentered}6 to 11{\textperiodcentered}9], difference 0{\textperiodcentered}5 ETDRS letters [-1{\textperiodcentered}1 to 2{\textperiodcentered}1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31\%], RHINE n=137 [43\%]), faricimab PTI (n=106 [34\%], n=119 [37\%]), and aflibercept every 8 weeks (n=102 [33\%], n=113 [36\%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.},
	issn = {1474-547X},
	doi = {10.1016/S0140-6736(22)00018-6},
	author = {Wykoff, Charles C and Abreu, Francis and Adamis, Anthony P and Basu, Karen and Eichenbaum, David A and Haskova, Zdenka and Lin, Hugh and Loewenstein, Anat and Mohan, Shaun and Pearce, Ian A and Sakamoto, Taiji and Schlottmann, Patricio G and Silverman, David and Sun, Jennifer K and Wells, John A and Willis, Jeffrey R and Tadayoni, Ramin and YOSEMITE and RHINE Investigators}
}
@article {1651372,
	title = {Implementation and Evaluation of Integrating an Electronic Health Record With the ACGME Case Log System},
	journal = {J Grad Med Educ},
	year = {2022},
	author = {Xiao, G and Sikder, S and Woreta, F and Boland, MV}
}
@article {1517188,
	title = {XDream: Finding preferred stimuli for visual neurons using generative networks and gradient-free optimization},
	journal = {PLoS Comput Biol},
	volume = {16},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {e1007973},
	abstract = {A longstanding question in sensory neuroscience is what types of stimuli drive neurons to fire. The characterization of effective stimuli has traditionally been based on a combination of intuition, insights from previous studies, and luck. A new method termed XDream (EXtending DeepDream with real-time evolution for activation maximization) combined a generative neural network and a genetic algorithm in a closed loop to create strong stimuli for neurons in the macaque visual cortex. Here we extensively and systematically evaluate the performance of XDream. We use ConvNet units as in silico models of neurons, enabling experiments that would be prohibitive with biological neurons. We evaluated how the method compares to brute-force search, and how well the method generalizes to different neurons and processing stages. We also explored design and parameter choices. XDream can efficiently find preferred features for visual units without any prior knowledge about them. XDream extrapolates to different layers, architectures, and developmental regimes, performing better than brute-force search, and often better than exhaustive sampling of \&gt;1 million images. Furthermore, XDream is robust to choices of multiple image generators, optimization algorithms, and hyperparameters, suggesting that its performance is locally near-optimal. Lastly, we found no significant advantage to problem-specific parameter tuning. These results establish expectations and provide practical recommendations for using XDream to investigate neural coding in biological preparations. Overall, XDream is an efficient, general, and robust algorithm for uncovering neuronal tuning preferences using a vast and diverse stimulus space. XDream is implemented in Python, released under the MIT License, and works on Linux, Windows, and MacOS.},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1007973},
	author = {Xiao, Will and Kreiman, Gabriel}
}
@article {1474191,
	title = {Diagnostic Test Efficacy of Meibomian Gland Morphology and Function},
	journal = {Sci Rep},
	volume = {9},
	number = {1},
	year = {2019},
	month = {2019 Nov 22},
	pages = {17345},
	abstract = {Meibomian gland dysfunction (MGD) is the leading cause of dry eye and proposed treatments are based on disease severity. Our purpose was to establish reliable morphologic measurements of meibomian glands for evaluating MGD severity. This retrospective, cross-sectional study included 100 MGD patients and 20 controls. The patients were classified into dry eye severity level (DESL) 1-4 based on symptoms and clinical parameters including tear-film breakup time, ocular staining and Schirmer I. The gland loss, length, thickness, density and distortion were analyzed. We compared the morphology between patients and controls; examined their correlations to meibum expressibility, quality, and DESL. Relative to controls, the gland thickness, density and distortion were elevated in patients (p \&lt; 0.001 for all tests). The area under the receiver operating characteristic curve was 0.98 (95\% confidence interval [CI], 0.96-1.0) for gland loss, and 0.96 (CI 0.91-1.0) for gland distortion, with a cutoff value of six distorted glands yielding a sensitivity of 93\% and specificity of 97\% for MGD diagnosis. The gland distortion was negatively correlated to the meibum expressibility (r = -0.53; p \&lt; 0.001) and DESL (r = -0.22, p = 0.018). In conclusion, evaluation of meibomian gland loss and distortion are valuable complementary clinical parameters to assess MGD status.},
	issn = {2045-2322},
	doi = {10.1038/s41598-019-54013-4},
	author = {Xiao, Jiaxin and Adil, Muhammed Yasin and Olafsson, Jonatan and Chen, Xiangjun and Utheim, {\O}ygunn A and R{\ae}der, Sten and Lagali, Neil S and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1511499,
	title = {Improved adherence and treatment outcomes with an engaging, personalized digital therapeutic in amblyopia},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 May 20},
	pages = {8328},
	abstract = {Given the prevalence of poor adherence to therapy and the biases of self-reporting across healthcare, we hypothesized that an engaging, personalized therapy may improve adherence and treatment outcomes in the home. We tested this hypothesis in the initial indication of amblyopia, a neurodevelopmental disorder for which available treatments are limited by low adherence. We designed a novel digital therapeutic that modifies patient-selected cinematic content in real-time into therapeutic visual input, while objectively monitoring adherence. The therapeutic design integrated a custom-designed headset that delivers precise visual input to each eye, computational algorithms that apply real-time therapeutic modifications to source content, a cloud-based content management system that enables treatment in the home, and a broad library of licensed content. In a proof-of-concept human study on the therapeutic, we found that amblyopic eye vision improved significantly after 12 weeks of treatment, with higher adherence than that of available treatments. These initial results support the utility of personalized therapy in amblyopia and may have broader relevance for improving treatment outcomes in additional indications.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-65234-3},
	author = {Xiao, Scott and Gaier, Eric D and Mazow, Malcolm L and Stout, Ann U and Travers, Dean A and Angjeli, Endri and Wu, Hank C and Binenbaum, Gil and Hunter, David G}
}
@article {1466905,
	title = {Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity},
	journal = {Am J Ophthalmol},
	volume = {209},
	year = {2020},
	month = {2020 Jan},
	pages = {160-167},
	abstract = {PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. STUDY POPULATION: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P\&nbsp;=\&nbsp;0.006, P\&nbsp;= 0.016) and obstructive MGD (P\&nbsp;=\&nbsp;0.008, P\&nbsp;= 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P \&lt; 0.01 and P \&lt; 0.006, respectively). CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.09.005},
	author = {Xiao, Jiaxin and Adil, Muhammed Yasin and Chen, Xiangjun and Utheim, {\O}ygunn A and R{\ae}der, Sten and T{\o}nseth, Kim Alexander and Lagali, Neil S and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1629476,
	title = {Randomized Controlled Trial of a Dichoptic Digital Therapeutic for Amblyopia},
	journal = {Ophthalmology},
	volume = {129},
	number = {1},
	year = {2022},
	month = {2022 Jan},
	pages = {77-85},
	abstract = {PURPOSE: Digital therapeutics are a new class of interventions that are software driven and are intended to treat various conditions. We developed and evaluated a dichoptic digital therapeutic for amblyopia, a neurodevelopmental disorder for which current treatments may be limited by poor adherence and residual vision deficits. DESIGN: Randomized controlled trial. PARTICIPANTS: One hundred five children 4 to 7 years of age with amblyopia were enrolled at 21 academic and community sites in the United States. Participants were randomized 1:1 to the treatment or comparison group, stratified by site. METHODS: We conducted a phase 3 randomized controlled trial to evaluate the safety and efficacy of a dichoptic digital therapeutic for amblyopia. Participants in the treatment group used the therapeutic at home for 1 hour per day, 6 days per week and wore glasses full-time. Participants in the comparison group continued wearing glasses full-time alone. MAIN OUTCOME MEASURES: The primary efficacy outcome was change in amblyopic eye visual acuity (VA) from baseline at 12 weeks, and VA was measured by masked examiners. Safety was evaluated using the frequency and severity of study-related adverse events. Primary analyses were conducted using the intention-to-treat population. RESULTS: Between January 16, 2019, and January 15, 2020, 105 participants were enrolled; 51 were randomized to the treatment group and 54 were randomized to the comparison group. At 12 weeks, amblyopic eye VA improved by 1.8 lines (95\% confidence interval [CI], 1.4-2.3 lines; n\&nbsp;= 45) in the treatment group and by 0.8 lines (95\% CI, 0.4-1.3 lines; n\&nbsp;= 45) in the comparison group. At the planned interim analysis (adjusted α\&nbsp;= 0.0193), the difference between groups was significant (1.0 lines; P\&nbsp;= 0.0011; 96.14\% CI, 0.33-1.63 lines) and the study was stopped early for success, according to the protocol. No serious adverse events were reported. CONCLUSIONS: Our findings support the value of the therapeutic in clinical practice as an effective treatment. Future studies should evaluate the therapeutic compared with other methods and in additional patient populations.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.09.001},
	author = {Xiao, Scott and Angjeli, Endri and Wu, Hank C and Gaier, Eric D and Gomez, Stephanie and Travers, Dean A and Binenbaum, Gil and Langer, Robert and Hunter, David G and Repka, Michael X and Luminopia Pivotal Trial Group}
}
@article {1470975,
	title = {Visual Contrast Sensitivity Correlates to the Retinal Degeneration in Rhodopsin Knockout Mice},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {60},
	number = {13},
	year = {2019},
	month = {2019 Oct 01},
	pages = {4196-4204},
	abstract = {Purpose: Clinical manifestations of photoreceptor degeneration include gradual thinning of the outer nuclear layer (ONL) and progressive reduction of electroretinogram (ERG) amplitudes and vision loss. Although preclinical evaluations of treatment strategies greatly depend on rodent models, the courses of these changes in mice remain unclear. We thus sought to investigate the temporal correlations in changes of spatial vision, ERG response, and ONL thickness in mice with progressive photoreceptor degeneration. Methods: Adult wild-type (WT) mice and mice carrying rhodopsin deficiency (Rho-/-), a frequently used mouse model of human retinitis pigmentosa, were selected for investigation. Mouse spatial vision, including visual acuity (VA) and contrast sensitivity (CS), was determined using optomotor response (OMR) assays; ONL thickness was quantified by spectral-domain optical coherence tomography (SD-OCT), and ERG was performed to evaluate retinal functions. The mice were killed when they were 14 weeks old, and the cone photoreceptors in retinal sections were counted. Results: Spatial vision, ONL thickness, and ERG amplitudes remained stable in WT mice at all examined time points. While 6-week-old Rho-/- mice had VA, CS, as well as ERG responses similar to those of WT mice, progressive reductions in the spatial vision and retinal functions were recorded thereafter. Most tested 12-week-old Rho-/- mice had no visual-evoked OMR and ERG responses. Moreover, CS, but not VA, displayed a linear decline that was closely associated with ONL thinning, reduction of ERG amplitudes, and loss of cones. Conclusions: We presented a comprehensive study of the relation between the changes of spatial vision, retinal function, and ONL thickness in postnatal week (PW)6 to PW12 Rho-/- mice. CS is a more sensitive indicator of spatial vision compared to VA, although both are required as separate parameters for monitoring the visual changes in retina undergoing photoreceptor degeneration.},
	issn = {1552-5783},
	doi = {10.1167/iovs.19-26966},
	author = {Xiao, Jiaxin and Adil, Muhammed Yasin and Chang, Karen and Yu, Zicheng and Yang, Lanbo and Utheim, Tor P and Chen, Dong Feng and Cho, Kin-Sang}
}
@article {1309956,
	title = {Cryopreserved limbal lamellar keratoplasty for peripheral corneal and limbal reconstruction},
	journal = {Int J Ophthalmol},
	volume = {11},
	number = {4},
	year = {2018},
	month = {2018},
	pages = {699-702},
	abstract = {This study aimed to evaluate the outcomes and described the recovery process of cryopreserved limbal lamellar keratoplasty (CLLK) for peripheral corneal and limbal diseases. Thirteen eyes of 12 patients with a mean age of 41{\textpm}23.9y were included. The average follow-up was 12.1{\textpm}5.6mo. Stable ocular surface was achieved in all eyes at last follow-up. Epithelialization originated from both recipient and graft in 9 eyes. We conclude that CLLK compensates for the shortage of donor corneas and cryopreserved limbal grafts provide epithelialization sources in ocular surface reconstruction.},
	issn = {2222-3959},
	doi = {10.18240/ijo.2018.04.27},
	author = {Xie, Hua-Tao and Li, Jing and Liu, Yang and Jiang, Dong-Ling and Shen, Rui-Fen and Zhang, Ming-Chang}
}
@article {1109896,
	title = {Umbilical Cord Patch Transplantation for Corneal Perforations and Descemetoceles},
	journal = {J Ophthalmol},
	volume = {2017},
	year = {2017},
	month = {2017},
	pages = {2767053},
	abstract = {PURPOSE: To evaluate the clinical outcome of umbilical cord patch (UCP) transplantation for deep corneal ulcers with perforations and descemetoceles. METHODS: In this retrospective, noncomparative, interventional case series, 11 eyes of 11 patients with corneal perforation or descemetocele were included. The thickness and microstructure of UCP were measured. All eyes were treated with UCP and amniotic membrane transplantation for corneal reconstruction. Corneal ulcer healing, corneal thickness, anterior chamber formation, and best-corrected visual acuity (BCVA) were recorded and analyzed. RESULTS: The thickness of human UCP is 398.6 {\textpm} 102.8 μm (n = 5) with compact aligned fibers. The average age was 56.2 {\textpm} 15.8 (ranging from 22 to 75) years. The mean follow-up period was 7.1 {\textpm} 1.7 (ranging from 5 to 10) months. Four patients had descemetocele and 7 had perforation. The anterior chambers in all the 7 perforated corneas were formed at postoperative day 1. All patients regained a normal corneal thickness and smooth corneal surface within the first postoperative month. The vision improved in 10 eyes and remained unchanged in 1 eye. No recurrence nor side effects occurred during the follow-up. CONCLUSIONS: UCP can serve as an alternative material in the treatment of corneal perforations and descemetoceles. This treatment option is also beneficial in those countries with limited cornea donors and eye bank services.},
	issn = {2090-004X},
	doi = {10.1155/2017/2767053},
	author = {Xie, Hua-Tao and Zhao, Dan and Liu, Yang and Zhang, Ming-Chang}
}
@article {1586187,
	title = {Chemokine CCL5 promotes robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy},
	journal = {Proc Natl Acad Sci U S A},
	volume = {118},
	number = {9},
	year = {2021},
	month = {2021 Mar 02},
	abstract = {Ciliary neurotrophic factor (CNTF) is a leading therapeutic candidate for several ocular diseases and induces optic nerve regeneration in animal models. Paradoxically, however, although CNTF gene therapy promotes extensive regeneration, recombinant CNTF (rCNTF) has little effect. Because intraocular viral vectors induce inflammation, and because CNTF is an immune modulator, we investigated whether CNTF gene therapy acts indirectly through other immune mediators. The beneficial effects of CNTF gene therapy remained unchanged after deleting CNTF receptor alpha (CNTFRα) in retinal ganglion cells (RGCs), the projection neurons of the retina, but were diminished by depleting neutrophils or by genetically suppressing monocyte infiltration. CNTF gene therapy increased expression of C-C motif chemokine ligand 5 (CCL5) in immune cells and retinal glia, and recombinant CCL5 induced extensive axon regeneration. Conversely, CRISPR-mediated knockdown of the cognate receptor (CCR5) in RGCs or treating wild-type mice with a CCR5 antagonist repressed the effects of CNTF gene therapy. Thus, CCL5 is a previously unrecognized, potent activator of optic nerve regeneration and mediates many of the effects of CNTF gene therapy.},
	issn = {1091-6490},
	doi = {10.1073/pnas.2017282118},
	author = {Xie, Lili and Yin, Yuqin and Benowitz, Larry}
}
@article {1748516,
	title = {The oncomodulin receptor ArmC10 enables axon regeneration in mice after nerve injury and neurite outgrowth in human iPSC-derived sensory neurons},
	journal = {Sci Transl Med},
	volume = {15},
	number = {708},
	year = {2023},
	month = {2023 Aug 09},
	pages = {eadg6241},
	abstract = {Oncomodulin (Ocm) is a myeloid cell-derived growth factor that enables axon regeneration in mice and rats after optic nerve injury or peripheral nerve injury, yet the mechanisms underlying its activity are unknown. Using proximity biotinylation, coimmunoprecipitation, surface plasmon resonance, and ectopic expression, we have identified armadillo-repeat protein C10 (ArmC10) as a high-affinity receptor for Ocm. ArmC10 deletion suppressed inflammation-induced axon regeneration in the injured optic nerves of mice. ArmC10 deletion also suppressed the ability of lesioned sensory neurons to regenerate peripheral axons rapidly after a second injury and to regenerate their central axons after spinal cord injury in mice (the conditioning lesion effect). Conversely, Ocm acted through ArmC10 to accelerate optic nerve and peripheral nerve regeneration and to enable spinal cord axon regeneration in these mouse nerve injury models. We showed that ArmC10 is highly expressed in human-induced pluripotent stem cell-derived sensory neurons and that exposure to Ocm altered gene expression and enhanced neurite outgrowth. ArmC10 was also expressed in human monocytes, and Ocm increased the expression of immune modulatory genes in these cells. These findings suggest that Ocm acting through its receptor ArmC10 may be a useful therapeutic target for nerve repair and immune modulation.},
	keywords = {Animals, Axons, Ganglia, Spinal, Humans, Induced Pluripotent Stem Cells, Mice, Nerve Regeneration, Neuronal Outgrowth, Sensory Receptor Cells},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.adg6241},
	author = {Xie, Lili and Yin, Yuqin and Jayakar, Selwyn and Kawaguchi, Riki and Wang, Qing and Peterson, Sheri and Shi, Caleb and Turnes, Bruna Lenfers and Zhang, Zihe and Oses-Prieto, Juan and Li, Jian and Burlingame, Al and Woolf, Clifford J and Geschwind, Daniel and Rasband, Matthew and Benowitz, Larry I}
}
@article {1333933,
	title = {Biomarkers for Progenitor and Differentiated Epithelial Cells in the Human Meibomian Gland},
	journal = {Stem Cells Transl Med},
	volume = {7},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {887-892},
	abstract = {The meibomian gland (MG) is a sebaceous gland that secretes through a holocrine process. Because such secretion requires the destruction of MG acinar epithelial cells, they need constant renewal and differentiation. The processes that promote these regenerative events in the human MG are unknown, nor is it known how to distinguish MG progenitor and differentiated cells. We discovered that Lrig1 and DNase2 serve as biomarkers for human MG progenitor and differentiated cells, respectively. Lrig1 is expressed in MG basal epithelial cells in the acinar periphery, a location where progenitor cells originate in sebaceous glands. DNase2 is expressed in the differentiated epithelial cells of the MG central acinus. Furthermore, proliferation stimulates, and differentiation suppresses, Lrig1 expression in human MG epithelial cells. The opposite is true for DNase2 expression. Our biomarker identification may have significant value in clinical efforts to restore MG function and to regenerate MGs after disease-induced dropout. Stem Cells Translational Medicine 2018;7:887-892.},
	issn = {2157-6564},
	doi = {10.1002/sctm.18-0037},
	author = {Xie, Hua-Tao and Sullivan, David A and Chen, Di and Hatton, Mark P and Kam, Wendy R and Liu, Yang}
}
@article {1651228,
	title = {Establishment of a bi-layered tissue engineered conjunctiva using a 3D-printed melt electrowritten poly-(ε-caprolactone) scaffold},
	journal = {Int Ophthalmol},
	year = {2022},
	author = {Xie, J and Gao, Q and Del Prado, ZN and Venkateswaran, N and Mousa, HM and Salero, E and Ye, J and De Juan-Pardo, EM and Sabater, AL and Perez, VL}
}
@article {1638570,
	title = {Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells{\textquoteright} response to Pten deletion},
	journal = {Proc Natl Acad Sci U S A},
	volume = {119},
	number = {15},
	year = {2022},
	month = {2022 Apr 12},
	pages = {e2113751119},
	abstract = {SignificanceThe optic nerve conveys information from retinal ganglion cells (RGCs) to visual processing areas of the brain. Although this pathway normally cannot regenerate when injured nor in degenerative diseases such as glaucoma, this failure can be partially reversed by eliciting a controlled immune reaction in the eye. We show here that the chemokine SDF1 (stromal cell-derived factor 1) is an important contributor to this phenomenon. SDF1 is produced by infiltrative monocytes and acts through its cognate receptor to enhance RGC survival, promote optic nerve regeneration, and sensitize subtypes of RGCs that normally fail to respond to a complementary treatment to exhibit robust, long-distance regeneration. These findings establish SDF1 as an important therapeutic candidate for repairing the injured optic nerve.},
	keywords = {Axons, Chemokine CXCL12, Humans, Monocytes, Nerve Regeneration, Optic Nerve Injuries, PTEN Phosphohydrolase, Retinal Ganglion Cells},
	issn = {1091-6490},
	doi = {10.1073/pnas.2113751119},
	author = {Xie, Lili and Cen, Ling-Ping and Li, Yiqing and Gilbert, Hui-Ya and Strelko, Oleksandr and Berlinicke, Cynthia and Stavarache, Mihaela A and Ma, Madeline and Wang, Yongting and Cui, Qi and Kaplitt, Michael G and Zack, Donald J and Benowitz, Larry I and Yin, Yuqin}
}
@article {1483616,
	title = {Idelalisib inhibits vitreous-induced Akt activation and proliferation of retinal pigment epithelial cells from epiretinal membranes},
	journal = {Exp Eye Res},
	volume = {190},
	year = {2020},
	month = {2020 Jan},
	pages = {107884},
	abstract = {Proliferative vitreoretinopathy (PVR) is a blinding fibrotic eye disease that develops in 8-10\% of patients who undergo primary retinal detachment-reparative surgery and in 40-60\% of patients with open-globe injury. At present, there is no pharmacological treatment for this devastating disease. Vitreal growth factors activate their respective receptors of cells in the vitreous, trigger their downstream signaling transduction (e.g. phosphoinositide 3 kinases (PI3Ks)/Akt), and drive cellular responses intrinsic to the pathogenesis of PVR. PI3Ks play a central role in experimental PVR. However, which isoform(s) are involved in PVR pathogenesis remain unknown. Herein, we show that p110δ, a catalytic subunit of receptor-regulated PI3K isoform δ, is highly expressed in epiretinal membranes from patients with PVR, and that idelalisib, a specific inhibitor of PI3Kδ, effectively inhibits vitreous-induced Akt activation, proliferation, migration and contraction of retinal pigment epithelial cells derived from an epiretinal membrane of a PVR patient. Small molecules of kinase inhibitors have shown great promise as a class of therapeutics for a variety of human diseases. The data herein suggest that idelalisib is a promising PVR prophylactic.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2019.107884},
	author = {Xin, Tianyi and Han, Haote and Wu, Wenyi and Huang, Xionggao and Cui, Jing and Matsubara, Joanne Aiko and Song, Jingyuan and Wang, Fang and Colyer, Marcus and Lei, Hetian}
}
@article {1635632,
	title = {Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors},
	journal = {Cell},
	year = {2022},
	month = {2022 Mar 02},
	abstract = {Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E.\&nbsp;faecalis, E.\&nbsp;faecium, and E.\&nbsp;hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of β-barrel pore-forming toxins with a β-barrel protrusion (designated the top domain) sitting atop the cap domain. Through a genome-wide CRISPR-Cas9 screen, we identify human leukocyte antigen class I (HLA-I) complex as a receptor for two members (Epx2 and Epx3), which preferentially recognize human HLA-I and homologous MHC-I of equine, bovine, and porcine, but not murine, origin. Interferon exposure, which stimulates MHC-I expression, sensitizes human cells and intestinal organoids to Epx2 and Epx3 toxicity. Co-culture with Epx2-harboring E.\&nbsp;faecium damages human peripheral blood mononuclear cells and intestinal organoids, and this toxicity is neutralized by an Epx2 antibody, demonstrating the toxin-mediated virulence of Epx-carrying Enterococcus.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2022.02.002},
	author = {Xiong, Xiaozhe and Tian, Songhai and Pan Yang and Lebreton, Francois and Bao, Huan and Sheng, Kuanwei and Yin, Linxiang and Chen, Pengsheng and Zhang, Jie and Qi, Wanshu and Ruan, Jianbin and Wu, Hao and Chen, Hong and Breault, David T and Wu, Hao and Earl, Ashlee M and Gilmore, Michael S and Jonathan Abraham and Dong, Min}
}
@article {603831,
	title = {Distinct Expression Patterns of AAV8 Vectors with Broadly Active Promoters from Subretinal Injections of Neonatal Mouse Eyes at Two Different Ages.},
	journal = {Adv Exp Med Biol},
	volume = {854},
	year = {2016},
	month = {2016},
	pages = {501-7},
	abstract = {The retinal expression patterns were analyzed following the injection of serotype 8 adeno-associated virus (AAV8) vectors that utilize two broadly active and commonly used sets of transcription regulatory sequences. These include the human cytomegalovirus (CMV) immediate early (IE) enhancer/promoter and the hybrid CAG element (also known as CAGGS or CBA) composed of a partial human CMV IE enhancer and the chicken β-actin promoter and intron. Subretinal delivery to postnatal day 0 (P0) or 6 (P6) mouse eyes resulted in efficient labeling of retinal cells, but with very distinct patterns. With P0 delivery, AAV8-CMV-GFP selectively labelled photoreceptors, while AAV8-CAG-GFP efficiently labeled both outer and inner retinal neurons, including photoreceptors, horizontal cells, amacrine cells and retinal ganglion cells. With P6 delivery, both vectors led to efficient labeling of photoreceptors and M{\"u}ller glia cells, but not of inner retinal neurons. Our results suggest that the cell types that express the genes encoded by subretinally delivered AAV8 vectors are determined by both the timing of the injection and the regulatory sequences.},
	issn = {0065-2598},
	doi = {10.1007/978-3-319-17121-0_67},
	author = {Xiong, Wenjun and Cepko, Constance}
}
@article {1598030,
	title = {Altered brain network centrality in patients with mild cognitive impairment: an fMRI study using a voxel-wise degree centrality approach},
	journal = {Aging (Albany NY)},
	volume = {13},
	number = {11},
	year = {2021},
	month = {2021 Jun 09},
	pages = {15491-15500},
	abstract = {PURPOSE: Previous studies in patients with Alzheimer{\textquoteright}s disease have shown amyloid beta accumulation in the brain and abnormal brain activity, with mild cognitive impairment (MCI) in early stages of the disease. The aim of the current study was to investigate functional connectivity in patients with MCI. METHODS: We recruited 24 subjects in total, including 12 patients with MCI (6 men and 6 women) and 12 healthy controls (HCs) (6 men and 6 women), matched for age, gender, and lifestyle factors. All subjects underwent resting-state functional magnetic resonance imaging scans and voxel-wise degree centrality (DC) was used to evaluate alterations in the strength of brain network connectivity. RESULTS: The DC value of the left inferior temporal gyrus was lower in MCI but significantly higher in the right fusiform gyrus and the left supplementary motor area, compared with HCs. The DC value in left inferior temporal gyrus correlated positively with disease duration and negatively with Mini-Mental State Examination. ROC curve analysis of brain regions showed acceptable specificity and accuracy of DC values between MCIs and HCs in the area under the curve (right fusiform gyrus, 0.955; left supplementary motor area, 0.992; left inferior temporal gyrus, 1.000). CONCLUSIONS: Abnormal functional connectivity in brain regions of patients with MCI may reflect the pathological process of Alzheimer{\textquoteright}s disease development and could prove useful in clinical diagnosis and treatment.},
	issn = {1945-4589},
	doi = {10.18632/aging.203105},
	author = {Xiong, Jing and Yu, Chao and Su, Ting and Ge, Qian-Min and Shi, Wen-Qing and Tang, Li-Ying and Shu, Hui-Ye and Pan, Yi-Cong and Liang, Rong-Bin and Li, Qiu-Yu and Shao, Yi}
}
@article {1623360,
	title = {Auditory Reminder Cues to Promote Proactive Scanning on Approach to Intersections in Drivers With Homonymous Hemianopia: Driving With Hemianopia, IX},
	journal = {JAMA Ophthalmol},
	volume = {140},
	number = {1},
	year = {2022},
	month = {2022 Jan 01},
	pages = {75-78},
	abstract = {Importance: Individuals with homonymous hemianopia (HH) are permitted to drive in some jurisdictions. They could compensate for their hemifield vision loss by scanning toward the blind side. However, some drivers with HH do not scan adequately well to the blind side when approaching an intersection, resulting in delayed responses to hazards. Objective: To evaluate whether auditory reminder cues promoted proactive scanning on approach to intersections. Design, Setting, and Participants: This cross-sectional, single-visit driving simulator study was conducted from October 2018 to May 2019 at a vision rehabilitation research laboratory. A volunteer sample of individuals with HH without visual neglect are included in this analysis. This post hoc analysis was completed in July and August 2020. Main Outcomes and Measures: Participants completed drives with and without scanning reminder cues (a single tone from a speaker on the blind side). Scanning was quantified by the percentage of intersections at which an early large scan was made (a scan with a head movement of at least 20{\textdegree} made before 30 m from the intersection). Responses to motorcycle hazards at intersections were quantified by the time to the first fixation and the time to the horn-press response. Results: Sixteen individuals were recruited and completed the study. Two were subsequently excluded from analyses. Thus, data from 14 participants (median [IQR] age, 54 [36-66] years; 13 men [93\%]) were included. Stroke was the primary cause of the HH (10 participants [71\%]). Six (43\%) had right-sided HH. Participants were more likely to make an early large scan to the blind side in drives with vs without cues (65\% vs 45\%; difference, 20\% [95\% CI, 5\%-37\%]; P \&lt; .001). When participants made an early large scan to the blind side, they were faster to make their first fixation on blind-side motorcycles (mean [SD], 1.77 [1.34] vs 3.88 [1.17] seconds; difference, -2.11 [95\% CI, -2.46 to -1.75] seconds; P \&lt; .001) and faster to press the horn (mean [SD], 2.54 [1.19] vs 4.54 [1.37] seconds; difference, -2.00 [95\% CI, -2.38 to -1.62] seconds; P \&lt; .001) than when they did not make an early scan. Conclusions and Relevance: This post hoc analysis suggests that auditory reminder cues may promote proactive scanning, which may be associated with faster responses to hazards. This hypothesis should be considered in future prospective studies.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.5007},
	author = {Xu, Jing and Emmermann, Birte and Bowers, Alex R}
}
@article {1709711,
	title = {Eye Swelling and Decreased Vision in a Patient With Autism},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {2},
	year = {2023},
	month = {2023 Jun 01},
	pages = {e63},
	keywords = {Autistic Disorder, Eye Diseases, Humans},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001832},
	author = {Xu, Jia and Zhang, Yanjia Jason and Gonzalez, Efren and Dohlman, Thomas H and Gaier, Eric D}
}
@article {1573125,
	title = {Anatomic Changes and Predictors of Angle Widening after Laser Peripheral Iridotomy: The Zhongshan Angle Closure Prevention Trial},
	journal = {Ophthalmology},
	volume = {128},
	number = {8},
	year = {2021},
	month = {2021 Aug},
	pages = {1161-1168},
	abstract = {PURPOSE: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy. DESIGN: Prospective observational study. PARTICIPANTS: Primary angle-closure suspects (PACSs) 50 to 70 years of age. METHODS: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o{\textquoteright}clock) or temporal or nasal locations (at or below 10:30 or 1:30 o{\textquoteright}clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 μm from the scleral spur (AOD750); poor angle widening, defined as the lowest quintile of change in mean AOD750; and poor angle opening, defined as residual PACS after LPI based on gonioscopy. MAIN OUTCOME MEASURES: Anatomic changes and predictors of angle widening and opening after LPI. RESULTS: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P \&lt; 0.006) after LPI, including greater AOD750 (P \&lt; 0.001). One hundred twenty eyes (26.4\%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P\&nbsp;= 0.004), smaller AOD750 (P \&lt; 0.001), and greater iris curvature (P \&lt; 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P \&lt; 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening. CONCLUSIONS: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.01.021},
	author = {Xu, Benjamin Y and Friedman, David S and Foster, Paul J and Jiang, Yu and Pardeshi, Anmol A and Jiang, Yuzhen and Munoz, Beatriz and Aung, Tin and He, Mingguang}
}
@article {1761791,
	title = {Telemedicine retinopathy of prematurity severity score (TeleROP-SS) versus modified activity score (mROP-ActS) retrospective comparison in SUNDROP cohort},
	journal = {Sci Rep},
	volume = {13},
	number = {1},
	year = {2023},
	month = {2023 Sep 14},
	pages = {15219},
	abstract = {Identifying and planning treatment for retinopathy of prematurity (ROP) using telemedicine is becoming increasingly ubiquitous, necessitating a grading system to help caretakers of at-risk infants gauge disease severity. The modified ROP Activity Scale (mROP-ActS) factors zone, stage, and plus disease into its scoring system, addressing the need for assessing ROP{\textquoteright}s totality of binocular burden via indirect ophthalmoscopy. However, there is an unmet need for an alternative score which could facilitate ROP identification and gauge disease improvement or deterioration specifically on photographic telemedicine exams. Here, we propose such a system (Telemedicine ROP Severity Score [TeleROP-SS]), which we have compared against the mROP-ActS. In our statistical analysis of 1568 exams, we saw that TeleROP-SS was able to return a score in all instances based on the gradings available from the retrospective SUNDROP cohort, while mROP-ActS obtained a score of 80.8\% in right eyes and 81.1\% in left eyes. For treatment-warranted ROP (TW-ROP), TeleROP-SS obtained a score of 100\% and 95\% in the right and left eyes respectively, while mROP-ActS obtained a score of 70\% and 63\% respectively. The TeleROP-SS score can identify disease improvement or deterioration on telemedicine exams, distinguish timepoints at which treatments can be given, and it has the adaptability to be modified as needed.},
	keywords = {Eye, Humans, Infant, Infant, Newborn, Ophthalmoscopy, Retinopathy of Prematurity, Retrospective Studies, Telemedicine},
	issn = {2045-2322},
	doi = {10.1038/s41598-023-42150-w},
	author = {Xu, Christine L and Adu-Brimpong, Joel and Moshfeghi, Henry P and Rosenblatt, Tatiana R and Yu, Michael D and Ji, Marco H and Wang, Sean K and Zaidi, Moosa and Ghoraba, Hashem and Michalak, Suzanne and Callaway, Natalia F and Kumm, Jochen and Nudleman, Eric and Wood, Edward H and Patel, Nimesh A and Stahl, Andreas and Lepore, Domenico and Moshfeghi, Darius M}
}
@article {1773506,
	title = {Driving Difficulties and Preferences of Advanced Driver Assistance Systems by Older Drivers With Central Vision Loss},
	journal = {Transl Vis Sci Technol},
	volume = {12},
	number = {10},
	year = {2023},
	month = {2023 Oct 03},
	pages = {7},
	abstract = {PURPOSE: The purpose of this study was to investigate driving difficulties and Advanced Driver Assistance Systems (ADAS) use and preferences of drivers with and without central vision loss (CVL). METHODS: Fifty-eight drivers with CVL (71 {\textpm} 13 years) and 68 without (72 {\textpm} 8 years) completed a telephone questionnaire. They rated their perceived driving difficulty and usefulness of technology support in 15 driving situations under good (daytime) and reduced visibility conditions, and reported their use experience and preferences for 12 available ADAS technologies. RESULTS: Drivers with CVL reported more difficulty (P = 0.002) and greater usefulness of technology support (P = 0.003) than non-CVL drivers, especially in reduced visibility conditions. Increased driving difficulty was associated with higher perceived technology usefulness (r = 0.34, P \&lt; 0.001). Dealing with blind spot road users, glare, unexpected pedestrians, and unfamiliar areas were perceived as the most difficult tasks that would benefit from technology support. Drivers with CVL used more advanced ADAS features than non-CVL drivers (P = 0.02), preferred to own the blind spot warning, pedestrian warning, and forward collision avoidance systems, and favored ADAS support that provided both information and active intervention. The perceived benefits of and willingness to own ADAS technologies were high for both groups. CONCLUSIONS: Drivers with CVL used more advanced ADAS and perceived greater usefulness of driver assistance technology in supporting difficult driving situations, with a strong preference for collision prevention support. TRANSLATIONAL RELEVANCE: This study highlights the specific technology needs and preferences of older drivers with CVL, which can inform future ADAS development, evaluation, and training tailored to this group.},
	keywords = {Accidents, Traffic, Automobile Driving},
	issn = {2164-2591},
	doi = {10.1167/tvst.12.10.7},
	author = {Xu, Jing and Hutton, Abbie and Dougherty, Bradley E and Bowers, Alex R}
}
@article {1603860,
	title = {Endoscopic Cyclophotocoagulation in Boston Keratoprosthesis Type II},
	journal = {Ophthalmol Glaucoma},
	volume = {5},
	number = {1},
	year = {2022},
	month = {2022 Jan-Feb},
	pages = {120-123},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.07.002},
	author = {Xu, Christine and Chen, Teresa C and Chodosh, James and Eliott, Dean and Mukai, Shizuo and Shen, Lucy Q and Vavvas, Demetrios G and Young, Lucy H and Lin, Michael M}
}
@article {1653571,
	title = {Insights From the Eye for Patients With Kidney Transplant},
	journal = {Transplant Proc},
	year = {2022},
	month = {2022 Sep 09},
	abstract = {The eye and the kidney share structural and developmental similarities on a cellular and clinical level, and they are often affected by the same disease processes. Performing an eye exam to look for signs of conditions such as hypertension and diabetes can provide a helpful window into the health of the kidney. Patients with kidney transplants (KT) are a unique population that require close monitoring. These patients are maintained on a number of immunosuppressive medications and may face complications such as medication side effects, infections, and graft rejection. Patients with KT are at higher risk of both infectious and noninfectious eye conditions related to underlying systemic disease or use of immunosuppressive medications. Screening for eye conditions is important because preserving visual function is integral to quality of life, and also because the eye exam can help with early detection and treatment of systemic conditions. Here we describe some of the common eye findings and conditions in patients with KT. We recommend that patients with KT receive annual eye exams, and we hope that the information provided here can help nephrologists become more familiar with eye findings and identify situations where a referral to ophthalmology is warranted.},
	issn = {1873-2623},
	doi = {10.1016/j.transproceed.2022.07.008},
	author = {Xu, Christine and Prager, Alisa J and Alonso, Carolyn D and Pawar, Aditya S}
}
@article {1532326,
	title = {Anti-fibrosis potential of pirarubicin via inducing apoptotic and autophagic cell death in rabbit conjunctiva},
	journal = {Exp Eye Res},
	volume = {200},
	year = {2020},
	month = {2020 Nov},
	pages = {108215},
	abstract = {This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5\&nbsp;min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2{\textquoteright},7{\textquoteright}-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5\&nbsp;μmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15\&nbsp;μmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600\&nbsp;μmol/L MMC, both 7.5\&nbsp;μmol/L and 15\&nbsp;μmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5\&nbsp;μmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5\&nbsp;μmol/L prevented postoperative conjunctival fibrosis in an animal model.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.108215},
	author = {Xu, Li-Juan and Rong, Shi-Song and Xu, Ye-Sheng and Zheng, Li-Bin and Qiu, Wen-Ya and Zhang, Xia and Jiang, Lou-Jing and Duan, Run-Ping and Tian, Tian and Yao, Yu-Feng}
}
@article {1647898,
	title = {Driving With Hemianopia X: Effects of Cross Traffic on Gaze Behaviors and Pedestrian Responses at Intersections},
	journal = {Front Hum Neurosci},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {938140},
	abstract = {Purpose: We conducted a driving simulator study to investigate the effects of monitoring intersection cross traffic on gaze behaviors and responses to pedestrians by drivers with hemianopic field loss (HFL). Methods: Sixteen HFL and sixteen normal vision (NV) participants completed two drives in an urban environment. At 30 intersections, a pedestrian ran across the road when the participant entered the intersection, requiring a braking response to avoid a collision. Intersections with these pedestrian events had either (1) no cross traffic, (2) one approaching car from the side opposite the pedestrian location, or (3) two approaching cars, one from each side at the same time. Results: Overall, HFL drivers made more (p \&lt; 0.001) and larger (p = 0.016) blind- than seeing-side scans and looked at the majority (\&gt;80\%) of cross-traffic on both the blind and seeing sides. They made more numerous and larger gaze scans (p \&lt; 0.001) when they fixated cars on both sides (compared to one or no cars) and had lower rates of unsafe responses to blind- but not seeing-side pedestrians (interaction, p = 0.037). They were more likely to demonstrate compensatory blind-side fixation behaviors (faster time to fixate and longer fixation durations) when there was no car on the seeing side. Fixation behaviors and unsafe response rates were most similar to those of NV drivers when cars were fixated on both sides. Conclusion: For HFL participants, making more scans, larger scans and safer responses to pedestrians crossing from the blind side were associated with looking at cross traffic from both directions. Thus, cross traffic might serve as a reminder to scan and provide a reference point to guide blind-side scanning of drivers with HFL. Proactively checking for cross-traffic cars from both sides could be an important safety practice for drivers with HFL.},
	issn = {1662-5161},
	doi = {10.3389/fnhum.2022.938140},
	author = {Xu, Jing and Baliutaviciute, Vilte and Swan, Garrett and Bowers, Alex R}
}
@article {1619422,
	title = {Ocular Biometric Risk Factors for Progression of Primary Angle Closure Disease: The Zhongshan Angle Closure Prevention Trial},
	journal = {Ophthalmology},
	volume = {129},
	number = {3},
	year = {2022},
	month = {2022 03},
	pages = {267-275},
	abstract = {PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective, observational study. PARTICIPANTS: Six hundred forty-three mainland Chinese with untreated PACS. METHODS: Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Six-year progression from PACS to PAC or AAC. RESULTS: Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 μm from the scleral spur (AOD500; odds ratio [OR], 1.10 per 0.01-mm decrease; P\&nbsp;= 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P\&nbsp;= 0.01), and older age (OR, 1.11 per 1-year increase; P\&nbsp;= 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P\&nbsp;= 0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR, 3.10; P\&nbsp;= 0.002) and IC (OR, 2.48; P\&nbsp;= 0.014) measurements and 59 years of age or older (OR, 2.68; P\&nbsp;= 0.01) at baseline showed higher odds of progression (AUC, 0.72). CONCLUSIONS: Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not.},
	keywords = {Aged, Anterior Eye Segment, Asians, Biometry, China, Disease Progression, Female, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Male, Middle Aged, Prospective Studies, Risk Factors, Tomography, Optical Coherence, Tonometry, Ocular, Ultrasonography},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.10.003},
	author = {Xu, Benjamin Y and Friedman, David S and Foster, Paul J and Jiang, Yu and Porporato, Natalia and Pardeshi, Anmol A and Jiang, Yuzhen and Munoz, Beatriz and Aung, Tin and He, Mingguang}
}
@article {1655717,
	title = {Combined Model of OCT Angiography and Structural OCT Parameters to Predict Paracentral Visual Field Loss in Primary Open-Angle Glaucoma},
	journal = {Ophthalmol Glaucoma},
	volume = {6},
	number = {3},
	year = {2023},
	month = {2023 May-Jun},
	pages = {255-265},
	abstract = {PURPOSE: To assess a model combining OCT angiography (OCTA) and OCT parameters to predict the severity of paracentral visual field (VF) loss in primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study. PARTICIPANTS: Forty-four patients with POAG and 42 control subjects underwent OCTA and OCT imaging with a swept-source OCT device. METHODS: The circumpapillary microvasculature was quantified for vessel density (cpVD) and flow (cpFlow) after delineation of Bruch{\textquoteright}s membrane opening and removal of large vessels. Retinal nerve fiber layer thickness (RNFLT) and Bruch{\textquoteright}s membrane opening-minimum rim width (BMO-MRW) were measured from structural OCT. Paracentral total deviation (PaTD) was defined as the average of the total deviation values within the central 10 degrees on Humphrey VF testing (24-2) for upper and lower hemifields. The OCT and OCTA parameters were measured in the affected hemisphere corresponding to the hemifield with lower PaTD for POAG patients. Models were created to predict affected PaTD based on RNFLT alone; RNFLT and BMO-MRW; OCTA alone; or RNFLT, BMO-MRW and OCTA parameters. The models were compared using coefficient of determination (r2) and Bayesian information criterion (BIC) score. Bayesian information criterion decrease of >=6 indicates strong evidence for model improvement. MAIN OUTCOME MEASURES: Performance of models containing OCT and OCTA parameters in predicting PaTD. RESULTS: Patients with POAG and controls were similar in age and sex (65.9 {\textpm} 9.5 years and 38.4\% male overall, P >= 0.56 for both). Average RNFLT, minimum RNFLT, average BMO-MRW, minimum BMO-MRW, cpVD, and cpFlow were all significantly lower (all P \&lt; 0.001) in the affected hemisphere in patients with POAG than in controls. In patients with POAG, the average mean deviation was -4.33 {\textpm} 3.25 dB; the PaTD of the affected hemifield averaged -4.55 {\textpm} 5.26 dB and correlated significantly with both OCTA and structural OCT parameters (r >= 0.43, P <= 0.004 for all). The model containing RNFLT, BMO-MRW, and OCTA parameters was superior in predicting affected PaTD (r2\&nbsp;= 0.47, BIC\&nbsp;= 290.7), with higher r2 and lower BIC compared with all 3 other models. CONCLUSIONS: A combined model of OCTA and structural OCT parameters can predict the severity of paracentral VF loss of the affected hemifield, supporting clinical utility of OCTA in patients with POAG with paracentral VF loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Angiography, Bayes Theorem, Cross-Sectional Studies, Female, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Male, Optic Disk, Retinal Ganglion Cells, Scotoma, Tomography, Optical Coherence, Visual Fields},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2022.10.001},
	author = {Xu, Christine and Saini, Chhavi and Wang, Mengyu and Devlin, Julia and Wang, Haobing and Greenstein, Scott H and Brauner, Stacey C and Shen, Lucy Q}
}
@article {1517213,
	title = {Mislocalization of cone nuclei impairs cone function in mice},
	journal = {FASEB J},
	year = {2020},
	month = {2020 Jun 15},
	abstract = {The nuclei of cone photoreceptors are located on the apical side of the outer nuclear layer (ONL) in vertebrate retinas. However, the functional role of this evolutionarily conserved localization of cone nuclei is unknown. We previously showed that Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes) are essential for the apical migration of cone nuclei during development. Here, we developed an efficient genetic strategy to disrupt cone LINC complexes in mice. Experiments with animals from both sexes revealed that disrupting cone LINC complexes resulted in mislocalization of cone nuclei to the basal side of ONL in mouse retina. This, in turn, disrupted cone pedicle morphology, and appeared to reduce the efficiency of synaptic transmission from cones to bipolar cells. Although we did not observe other developmental or phototransduction defects in cones with mislocalized nuclei, their dark adaptation was impaired, consistent with a deficiency in chromophore recycling. These findings demonstrate that the apical localization of cone nuclei in the ONL is required for the timely dark adaptation and efficient synaptic transmission in cone photoreceptors.},
	issn = {1530-6860},
	doi = {10.1096/fj.202000568R},
	author = {Xue, Yunlu and Razafsky, David and Hodzic, Didier and Kefalov, Vladimir J}
}
@article {1732571,
	title = {Gene Therapies for Retinitis Pigmentosa that Target Glucose Metabolism},
	journal = {Cold Spring Harb Perspect Med},
	year = {2023},
	month = {2023 Jul 17},
	abstract = {Retinitis pigmentosa is a blinding disease wherein rod photoreceptors are affected first, due to the expression of a disease gene, leading to the loss of dim light vision. In many cases, cones do not express the disease gene, yet they are also affected and eventually die, typically after most of the rods in their neighborhood have died. The cause of secondary cone death is unclear. Photoreceptors are one of the most energy-demanding cell types in the body and consume a high amount of glucose. At an early stage of degeneration, the cones appear to have a shortage of glucose to fuel their metabolism. This review focuses on gene therapy approaches that address this potential metabolic shortcoming.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a041289},
	author = {Xue, Yunlu and Cepko, Constance L}
}
@article {1677626,
	title = {Sociodemographic and Geographic Variation in Access to Neuro-Ophthalmologists in the United States},
	journal = {J Neuroophthalmol},
	volume = {43},
	number = {2},
	year = {2023},
	month = {2023 Jun 01},
	pages = {149-152},
	abstract = {BACKGROUND: Neuro-ophthalmologists have expertise in rare and complex disorders, but the ability of patients to access neuro-ophthalmic care has not been examined at a nationwide level. METHODS: Using the 2020 directory of all 502 members of the North American Neuro-Ophthalmology Society as a reference, we found the practice locations of 461 confirmed practicing members and converted each street address to latitude and longitude coordinates. We calculated the travel distance and time from each census tract to the nearest practice location and calculated population-weighted averages by state, region, and other prespecified factors. Choropleth maps were used to visualize the distribution of travel distances and times across the United States. RESULTS: California had the most practicing neuro-ophthalmologists out of any state (50), whereas 4 states (DE, MT, SD, and WY) had none. Washington, DC and MA had the most neuro-ophthalmologists per capita. The average travel distance and time to the nearest neuro-ophthalmologists were found to be 40.90 miles and 46.50 minutes, respectively, although a large portion of western plains and mountain regions had travel times of over 120 minutes. Patients in rural areas had longer travel times than those in urban areas, and Native American patients had the longest travel times of any racial or ethnic group. CONCLUSION: The travel time to see a neuro-ophthalmologist varies widely by state, region, and rurality, with Native American patients and rural patients being disproportionately affected. By identifying the areas with the greatest travel burdens, future policies can work to alleviate these potential barriers to care.},
	keywords = {Health Services Accessibility, Humans, Ophthalmologists, Rural Population, Time Factors, Travel, United States},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000001821},
	author = {Xue, Katie and Feng, Yilin and Tam, Vicky and Lin, Chun Chieh and De Lott, Lindsey B and Hamedani, Ali G}
}
@article {1589753,
	title = {AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa},
	journal = {Elife},
	volume = {10},
	year = {2021},
	month = {2021 04 13},
	abstract = {Retinitis pigmentosa (RP) is an inherited retinal disease affecting \&gt;20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high-acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a disease gene-agnostic therapy, we screened 20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb) and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.},
	issn = {2050-084X},
	doi = {10.7554/eLife.66240},
	author = {Xue, Yunlu and Wang, Sean K and Rana, Parimal and West, Emma R and Hong, Christin M and Feng, Helian and Wu, David M and Cepko, Constance L}
}
@article {1698401,
	title = {Chromophore supply modulates cone function and survival in retinitis pigmentosa mouse models},
	journal = {Proc Natl Acad Sci U S A},
	volume = {120},
	number = {23},
	year = {2023},
	month = {2023 Jun 06},
	pages = {e2217885120},
	abstract = {Retinitis pigmentosa (RP) is an ocular disease characterized by the loss of night vision, followed by the loss of daylight vision. Daylight vision is initiated in the retina by cone photoreceptors, which are gradually lost in RP, often as bystanders in a disease process that initiates in their neighboring rod photoreceptors. Using physiological assays, we investigated the timing of cone electroretinogram (ERG) decline in RP mouse models. A correlation between the time of loss of the cone ERG and the loss of rods was found. To investigate a potential role of the visual chromophore supply in this loss, mouse mutants with alterations in the regeneration of the retinal chromophore, 11-cis retinal, were examined. Reducing chromophore supply via mutations in Rlbp1 or Rpe65 resulted in greater cone function and survival in a RP mouse model. Conversely, overexpression of Rpe65 and Lrat, genes that can drive the regeneration of the chromophore, led to greater cone degeneration. These data suggest that abnormally high chromophore supply to cones upon the loss of rods is toxic to cones, and that a potential therapy in at least some forms of RP is to slow the turnover and/or reduce the level of visual chromophore in the retina.},
	keywords = {Animals, Color Vision, Disease Models, Animal, Mice, Retina, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, Retinitis Pigmentosa},
	issn = {1091-6490},
	doi = {10.1073/pnas.2217885120},
	author = {Xue, Yunlu and Sun, Xiaomei and Wang, Sean K and Collin, Gayle B and Kefalov, Vladimir J and Cepko, Constance L}
}
@article {1367192,
	title = {Image-guided evaluation and monitoring of treatment response in patients with dry eye disease},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {252},
	number = {6},
	year = {2014},
	pages = {857-872},
	author = {Qazi Y and Aggarwal S and Hamrah P}
}
@article {1363225,
	title = {Vascular anomalies of the head and neck: a review of genetics},
	journal = {Semin Ophthalmol},
	volume = {28},
	number = {5-6},
	year = {2013},
	month = {2013 Sep-Nov},
	pages = {257-66},
	abstract = {PURPOSE: Vascular anomalies comprise malformations, hemangiomas, and rare tumors. The commonality among these lesions is their origin in vascular endothelia. Most occur sporadically, but occasional inheritance is observed and thus allows genetic research and insight into etiology. This review highlights those vascular anomalies in which genetic inheritance has been demonstrated. METHODS: A comprehensive literature search was performed on PubMed. Fifty-five full-length articles were reviewed. RESULTS: Five categories of vascular anomalies with patterned inheritance were identified: arteriovenous malformation (AVM), capillary malformation (CM), lymphatic malformation (LM), venous malformation (VM), and infantile hemangioma (IH). Capillary and arteriovenous malformation subtypes are associated with a RASA-1 gene mutation and show autosomal dominant inheritance. VEGFR3 mutations have been associated with generalized forms of LM and lymphedema. Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance. Familial clustering and atopic disease are associated with infantile hemangioma, and gene expression varies with the developmental stage of these lesions. CONCLUSION: Most vascular anomalies occur sporadically, but several genes and genetic disorders have been associated with them. Specific forms of capillary malformation appear to be most convincingly associated with genomic errors. Further research promises new insights into the development of this diverse group of disorders.},
	keywords = {Arteriovenous Malformations, Capillaries, Head, Hemangioma, Humans, Lymphatic Abnormalities, Neck, p120 GTPase Activating Protein, Receptor, TIE-2, Vascular Diseases, Vascular Endothelial Growth Factor Receptor-3, Vascular Malformations, Veins},
	issn = {1744-5205},
	doi = {10.3109/08820538.2013.825279},
	author = {Yadav, Prashant and De Castro, Dawn K and Waner, Milton and Meyer, Lutz and Fay, Aaron}
}
@article {1677836,
	title = {Investigating the role of beliefs in influencing the hand-held and hands-free mobile phone use among pedestrians in India},
	journal = {Int J Inj Contr Saf Promot},
	volume = {30},
	number = {1},
	year = {2023},
	month = {2023 Mar},
	pages = {79-90},
	abstract = {Mobile phone distraction is a significant contributor to pedestrian injuries. However, mobile phone engagement among pedestrians has been scarcely explored in a developing country like India. The present study utilized the beliefs-based theory of planned behaviour to examine the association between pedestrian beliefs towards distracted walking (behavioural, normative, and control) and their mobile phone use frequencies. Based on a survey of 560 pedestrians (64.6\% males), it was found that the major use of mobile phones was for listening to music (30.7\%), followed by receiving a call (25\%), making a call (18.9\%), texting (9.8\%), navigation (8.5\%) and internet browsing (7.1\%). A series of multivariate ANOVAs and logistic regression models were developed to investigate the relationships between the beliefs and frequencies of mobile phone use in hands-free and hand-held conditions. Significant multivariate differences were found for behavioural and normative beliefs in hands-free conditions and all three types of beliefs in hand-held conditions. The frequency of mobile phone use was significantly predicted by normative beliefs (p \&lt; 0.001) in the hands-free condition, and by behavioural (p = 0.041) and normative beliefs (p = 0.004) in the hand-held condition. The findings may assist the road safety countermeasures in addressing the issue of pedestrian distraction.},
	keywords = {Accidents, Traffic, Attention, Cell Phone, Cell Phone Use, Female, Humans, India, Male, Pedestrians, Safety, Walking},
	issn = {1745-7319},
	doi = {10.1080/17457300.2022.2112235},
	author = {Yadav, Ankit Kumar and Choudhary, Sajid Shabir and Pawar, Nishant Mukund and Velaga, Nagendra R}
}
@article {313266,
	title = {Extruded, partially disintegrated, poly-HEMA orbital implant (AlphaSphere)},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {30},
	number = {4},
	year = {2014},
	month = {2014 Jul-Aug},
	pages = {e86-91},
	abstract = {A 54-year-old diabetic man underwent enucleation for endophthalmitis. Secondary implantation of a 2-hydroxyethyl methacrylate (HEMA) sphere (AlphaSphere, Addition Technology) was performed 2 weeks later. Six weeks after insertion, noninfectious disintegration of sutured tissue planes represented by Tenon{\textquoteright}s capsule, rectus muscle, and conjunctiva occurred, requiring removal of the fragmenting implant before uncontrolled extrusion occurred. Histopathologic analysis revealed an absence of infectious pathogens and no tissue necrosis, but rather breakup of the implant material that elicited a granulomatous response with sparse T-lymphocytes and almost no polymorphonuclear leukocytes. This distinctively designed poly-HEMA orbital implant incited a dramatic and irreversible host tissue response. Investigation of other cases will be necessary to determine the frequency of such a complication and should include rigorous histopathologic techniques.},
	keywords = {Device Removal, Endophthalmitis, Eye Enucleation, Glaucoma, Neovascular, Humans, Male, Middle Aged, Orbital Implants, Polyhydroxyethyl Methacrylate, Prosthesis Failure, Reoperation, Retrospective Studies, Surgical Wound Dehiscence},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e31829f3b5c},
	author = {Yadav, Prashant and Jakobiec, Frederick A and De Castro, Dawn K and Mendoza, Pia R and Fay, Aaron}
}
@article {1732521,
	title = {The potential use of non-fungible tokens (NFTs) in healthcare and medical research},
	journal = {PLOS Digit Health},
	volume = {2},
	number = {7},
	year = {2023},
	month = {2023 Jul},
	pages = {e0000312},
	abstract = {Non-fungible tokens (NFTs) are cryptographic assets recorded on the blockchain that can certify authenticity and ownership, and they can be used to monetize health data, optimize the process of receiving a hematopoietic stem cell transplant, and improve the distribution of solid organs for transplantation. Blockchain technology, including NFTs, provides equitable access to wealth, increases transparency, eliminates personal or institutional biases of intermediaries, reduces inefficiencies, and ensures accountability. Blockchain architecture is ideal for ensuring security and privacy while granting individuals jurisdiction over their own information, making it a unique solution to the current limitations of existing health information systems. NFTs can be used to give patients the option to monetize their health data and provide valuable data to researchers. Wearable technology companies can also give their customers the option to monetize their data while providing data necessary to improve their products. Additionally, the process of receiving a hematopoietic stem cell transplant and the distribution of solid organs for transplantation could benefit from the integration of NFTs into the allocation process. However, there are limitations to the technology, including high energy consumption and the need for regulatory guidance. Further research is necessary to fully understand the potential of NFTs in healthcare and how it can be integrated with existing health information technology. Overall, NFTs have the potential to revolutionize the healthcare sector, providing benefits such as improved access to health information and increased efficiency in the distribution of organs for transplantation.},
	issn = {2767-3170},
	doi = {10.1371/journal.pdig.0000312},
	author = {Yaghy, Antonio and Alberto, Nicole Rose I and Alberto, Isabelle Rose I and Bermea, Rene S and Ristovska, Ljubica and Yaghy, Maria and Hoyek, Sandra and Patel, Nimesh A and Celi, Leo Anthony}
}
@article {1688281,
	title = {Microcephaly and chorioretinopathy associated with TUBGCP4: a case report and a review of the literature},
	journal = {Ophthalmic Genet},
	volume = {44},
	number = {6},
	year = {2023},
	month = {2023 Dec},
	pages = {585-590},
	abstract = {BACKGROUND: Microcephaly and chorioretinopathy (MCCRP) is a rare autosomal recessive (AR) disorder characterized by microcephaly, developmental delay, chorioretinopathy, and visual impairment. We characterized the long-term phenotype of an additional patient with MCCRP associated with TUBCGP4 pathogenic variants and analysed previously reported cases in the literature. MATERIALS AND METHODS: Analysis of clinical and genetic data of a patient with TUBGCP4-related MCCRP followed for more than 19 years and literature search for previously reported patients with TUBCGP4 variants using PubMed, Scopus, and Google Scholar. RESULTS: Molecular diagnosis using exome sequencing demonstrated two TUBCGP4 variants in trans: c.1669C\&gt;T (p.Arg557*) and c.1746 G\&gt;T (p.Leu582=). Clinical characteristics included microcephaly, microphthalmia, punched-out chorioretinal lesions, vision impairment, nystagmus, Tetralogy of Fallot and neurodevelopmental delay. Another six previously reported cases of TUBCGP4-related MCCRP were identified. Their clinical and genetic characteristics are compared. CONCLUSIONS: TUBCGP4-related microcephaly and chorioretinopathy, is a rare autosomal recessive neuro-ophthalmic disorder. Clinical characteristics in our proband have remained stable for two decades. The pathophysiology of this syndrome is not yet fully understood.},
	keywords = {Choroid Diseases, Eye, Family, Humans, Microcephaly, Microtubule-Associated Proteins, Phenotype, Retinal Diseases},
	issn = {1744-5094},
	doi = {10.1080/13816810.2023.2170424},
	author = {Yahalom, Claudia and Woods, Russell L and Akula, James D and Tan, Wen-Hann and Fulton, Anne}
}
@article {1664965,
	title = {Strategies for managing strabismus from oculomotor nerve palsy},
	journal = {J AAPOS},
	volume = {27},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {3-9},
	abstract = {Addressing ocular misalignment secondary to partial and complete oculomotor nerve palsy presents a special challenge to the strabismus surgeon, particularly when treating patients with binocular diplopia. We review the reported surgical options and, through illustrative cases, provide our own perspective on managing this disorder.},
	keywords = {Diplopia, Humans, Oculomotor Muscles, Oculomotor Nerve Diseases, Retrospective Studies, Strabismus, Vision, Binocular},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.11.017},
	author = {Yahalom, Claudia and Hunter, David G and Dagi, Linda R}
}
@article {1528411,
	title = {Recalcitrant Macular Hole Closure by Autologous Retinal Transplant Using the Peripheral Retina},
	journal = {Clin Ophthalmol},
	volume = {14},
	year = {2020},
	month = {2020},
	pages = {2301-2306},
	abstract = {Purpose: The peripheral adult human retina has been found to contain neuroepithelial stem cells. In this study, we examined the efficacy of an auto-transplant of peripheral retina into refractory macular holes (MH) from both anatomic and physiologic perspectives. Methods: The population consisted of four female patients aged 72, 82, 65 and 84 years (cases 1-4, respectively) with persistent refractory MH status; internal limiting membrane (ILM) peeling (case 1), ILM transplant (case 2), and inverted ILM (cases 3 and 4 with myopic MH). In all our cases, retinal grafts were harvested beyond the equator from the far retinal periphery using curved horizontal scissors and gently moved toward the MH using a forceps. A 25-G manipulator with a silicone ball tip was used to tuck the trimmed graft into the MH, followed by fluid-air exchange and infusion of silicone oil, which was removed three months later. Results: Partial restoration and integration of the outer retinal layer were confirmed on an OCT-B scan imaging. The visual acuity (VA) was improved in all cases: 1.2 to 1.0 logMAR (case 1), 2.0 to 1.3 logMAR (case 2), 2.3 to 1.4 logMAR (case 3) and 2.0 to 1.0 logMAR (case 4). Microperimetry showed improved retinal sensitivity in every case. No intra- or post-operative complications were observed. Conclusion: Under pathological conditions, the M{\"u}ller glia reportedly serves as a source of neuronal progenitor cells in regenerating retina, continuing to divide and migrate to the outer nuclear layer thus replacing lost photo-receptors. Although the histological findings remain unknown, the positive anatomic and physiologic outcomes of the auto-transplanted retinal flap in our series suggest that this technique may offer an effective option for treating recalcitrant MH. Further studies are warranted.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S236592},
	author = {Yamada, Keiko and Maeno, Takatoshi and Kusaka, Shunji and Arroyo, Jorge G and Yamada, Mitsunori}
}
@article {1351218,
	title = {Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain},
	journal = {Neuron},
	volume = {83},
	number = {1},
	year = {2014},
	month = {2014 Jul 02},
	pages = {122-34},
	abstract = {Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. We report that depletion of the NuRD complex by in\&nbsp;vivo RNAi and conditional knockout of the core NuRD subunit Chd4 profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses in the rodent cerebellar cortex in\&nbsp;vivo. By interfacing genome-wide sequencing of transcripts and ChIP-seq analyses, we uncover a network of repressed genes and distinct histone modifications at target gene promoters that are developmentally regulated by the NuRD complex in the cerebellum in\&nbsp;vivo. Finally, in a targeted in\&nbsp;vivo RNAi screen of NuRD target genes, we identify a program of NuRD-repressed genes that operate as critical regulators of presynaptic differentiation in the cerebellar cortex. Our findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that drives synaptic connectivity in the mammalian brain.},
	keywords = {Animals, Animals, Newborn, Brain Chemistry, Cells, Cultured, Chromatin Assembly and Disassembly, DNA-Binding Proteins, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Mice, Knockout, Mice, Transgenic, Promoter Regions, Genetic, Purkinje Cells, Rats, Rats, Long-Evans, Rats, Sprague-Dawley, Retinoblastoma-Binding Protein 4, Synapses},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2014.05.039},
	author = {Yamada, Tomoko and Yang, Yue and Hemberg, Martin and Yoshida, Toshimi and Cho, Ha Young and Murphy, J Patrick and Fioravante, Diasynou and Regehr, Wade G and Gygi, Steven P and Georgopoulos, Katia and Bonni, Azad}
}
@article {913556,
	title = {High-Resolution Imaging by Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Two Morphologically Distinct Types of Retinal Hard Exudates.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016},
	pages = {33574},
	abstract = {Histological studies from autopsy specimens have characterized hard exudates as a composition of lipid-laden macrophages or noncellular materials including lipid and proteinaceous substances (hyaline substances). However, the characteristics of hard exudates in living patients have not been examined due to insufficient resolution of existing equipment. In this study, we used adaptive optics scanning laser ophthalmoscopy (AO-SLO) to examine the characteristics of hard exudates in patients with retinal vascular diseases. High resolution imaging using AO-SLO enables morphological classification of retinal hard exudates into two types, which could not be distinguished either on fundus examination or by spectral domain optical coherence tomography (SD-OCT). One, termed a round type, consisted of an accumulation of spherical particles (average diameter of particles: 26.9 {\textpm} 4.4 μm). The other, termed an irregular type, comprised an irregularly shaped hyper-reflective deposition. The retinal thickness in regions with round hard exudates was significantly greater than the thickness in regions with irregular hard exudates (P = 0.01 {\textrightarrow}0.02). This differentiation of retinal hard exudates in patients by AO-SLO may help in understanding the pathogenesis and clinical prognosis of retinal vascular diseases.},
	issn = {2045-2322},
	doi = {10.1038/srep33574},
	author = {Yamaguchi, Muneo and Nakao, Shintaro and Kaizu, Yoshihiro and Kobayashi, Yoshiyuki and Nakama, Takahito and Arima, Mitsuru and Yoshida, Shigeo and Oshima, Yuji and Takeda, Atsunobu and Ikeda, Yasuhiro and Mukai, Shizuo and Ishibashi, Tatsuro and Sonoda, Koh-Hei}
}
@article {303841,
	title = {Correlation between Human Tear Cytokine Levels and Cellular Corneal Changes in Patients with Bacterial Keratitis by In Vivo Confocal Microscopy.},
	journal = {Invest Ophthalmol Vis Sci},
	year = {2014},
	month = {2014 Oct 16},
	abstract = {Purpose: To investigate bilateral tear cytokine levels in patients with unilateral bacterial keratitis (BK) as associated with in vivo confocal microscopic (IVCM) alterations in corneal nerves and dendritiform immune cells (DCs). Methods: Fifty-four (13 BK, 13 contralateral, 28 healthy controls) tear samples were collected prospectively and analyzed by multiplex microbeads assay. IVCM of the central cornea was performed on the same day and assessed for corneal nerve and DC alterations Results: Interleukin (IL)-1β, IL-6, and IL-8 were significantly elevated only in affected eyes (66.6{\textpm}26.8 ρg/ml, 7,174{\textpm}2,430, 810{\textpm}315, P=0.04, P\&lt;0.001 and P\&lt;0.001), compared to healthy controls (13.0{\textpm}4.0 ρg/ml, 171.8{\textpm}32.1, 56.5{\textpm}33.8). CCL-2, IL-10 and IL-17a were elevated only in contralateral eyes (813{\textpm}478 ρg/ml, 86.7{\textpm}38.3, 3,350{\textpm}881, P=0.02, P=0.01, P=0.04), compared to controls (73.7{\textpm}25.3 ρg/ml, 17.5 {\textpm}4.9, 1,350{\textpm}337). Triggering receptor expressed on myeloid cells (TREM)-1 was significantly elevated in both affected (551{\textpm}231 ρg/ml, P=0.02) and contralateral unaffected eyes (545{\textpm}298 ρg/ml, P=0.03), compared to controls (31.3{\textpm}12.4 ρg/ml). The density of DCs was significantly increased in both affected (226.9{\textpm}37.3 cells/mm2, P\&lt;0.001) and unaffected eyes (122.3{\textpm}23.7 cells/mm2, P\&lt;0.001) compared to controls (22.7{\textpm}5.9 cells/mm2). Subbasal nerve density significantly decreased in affected eyes (3,337{\textpm}1,615 μm/mm2, P\&lt;0.001) and contralateral eyes (13,230{\textpm}1,635 μm/mm2, P\&lt;0.001) compared to controls (21,200{\textpm}545 μm/mm2). IL-1β, IL-6 and IL-8 were significantly correlated with DC density (R=0.40, R=0.55 and R=0.31, all P\&lt;0.02) and nerve density (R=-0.30, R=-0.53 and R=-0.39, all P\&lt;0.01). Conclusions: Pro-inflammatory tear cytokines are elevated bilaterally in patients with unilateral BK, and are correlated strongly with alterations in DCs and nerve density as detected by IVCM.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-15411},
	author = {Yamaguchi, Takefumi and Calvacanti, Bernardo M and Cruzat, Andrea and Qazi, Yureeda and Ishikawa, Shizu and Osuka, Akinori and Lederer, James Arthur and Hamrah, Pedram}
}
@article {1363226,
	title = {Bilateral nerve alterations in a unilateral experimental neurotrophic keratopathy model: a lateral conjunctival approach for trigeminal axotomy},
	journal = {PLoS One},
	volume = {8},
	number = {8},
	year = {2013},
	month = {2013},
	pages = {e70908},
	abstract = {To study bilateral nerve changes in a newly developed novel mouse model for neurotrophic keratopathy by approaching the trigeminal nerve from the lateral fornix. Surgical axotomy of the ciliary nerve of the trigeminal nerve was performed in adult BALB/c mice at the posterior sclera. Axotomized, contralateral, and sham-treated corneas were excised on post-operative days 1, 3, 5, 7 and 14 and immunofluorescence histochemistry was performed with anti-β-tubulin antibody to evaluate corneal nerve density. Blink reflex was evaluated using a nylon thread. The survival rate was 100\% with minimal bleeding during axotomy and a surgical time of 8{\textpm}0.5 minutes. The blink reflex was diminished at day 1 after axotomy, but remained intact in the contralateral eyes in all mice. The central and peripheral subbasal nerves were not detectable in the axotomized cornea at day 1 (p\&lt;0.001), compared to normal eyes (101.3{\textpm}14.8 and 69.7{\textpm}12.0 mm/mm{\texttwosuperior} centrally and peripherally). Interestingly, the subbasal nerve density in the contralateral non-surgical eyes also decreased significantly to 62.4{\textpm}2.8 mm/mm{\texttwosuperior} in the center from day 1 (p\&lt;0.001), but did not change in the periphery (77.3{\textpm}11.7 mm/mm{\texttwosuperior}, P = 0.819). Our novel trigeminal axotomy mouse model is highly effective, less invasive, rapid, and has a high survival rate, demonstrating immediate loss of subbasal nerves in axotomized eyes and decreased subbasal nerves in contralateral eyes after unilateral axotomy. This model will allow investigating the effects of corneal nerve damage and serves as a new model for neurotrophic keratopathy.},
	keywords = {Animals, Axotomy, Conjunctiva, Cornea, Disease Models, Animal, Eye Diseases, Male, Mice, Mice, Inbred BALB C, Staining and Labeling, Time Factors, Trigeminal Nerve},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0070908},
	author = {Yamaguchi, Takefumi and Turhan, Aslihan and Harris, Deshea L and Hu, Kai and Pr{\"u}ss, Harald and von Andrian, Ulrich and Hamrah, Pedram}
}
@article {1517172,
	title = {Cell Atlas of The Human Fovea and Peripheral Retina},
	journal = {Sci Rep},
	volume = {10},
	number = {1},
	year = {2020},
	month = {2020 Jun 17},
	pages = {9802},
	abstract = {Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90\% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.},
	issn = {2045-2322},
	doi = {10.1038/s41598-020-66092-9},
	author = {Yan, Wenjun and Peng, Yi-Rong and van Zyl, Tav{\'e} and Regev, Aviv and Karthik Shekhar and Juric, Dejan and Sanes, Joshua R}
}
@article {1573097,
	title = {Multimodal Imaging Features of Optic Disc Drusen},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 Jan 21},
	abstract = {PURPOSE: Identify key en face multimodal imaging features of optic disc drusen (ODD). DESIGN: Retrospective cross-sectional study. METHODS: . SETTING: Single academic center. PATIENT OR STUDY POPULATION: 786 patients (age 10-82 years) with diagnostic codes for ODD or the term "optic disc drusen" in clinical notes extracted using natural language processing. INTERVENTION OR OBSERVATION PROCEDURES: Color fundus image, green-light and blue-light fundus autofluorescence (FAF), near-infrared reflectance (NIR), and enhanced-depth imaging optical coherence tomography (EDI-OCT). MAIN OUTCOME MEASURES: Ophthalmic imaging characteristics and sensitivity of en face imaging compared with EDI-OCT. RESULTS: 38 (61 eyes) of 786 patients had high-quality EDI-OCT and en face multimodal imaging. Green-light FAF had the highest sensitivity (96.8\%) and showed homogeneously hyperautofluorescence while blue-light FAF differentiated superficial and deep ODD by the heterogeneous brightness of FAF. Blue-light FAF (93.5\%) and NIR (91.8\%) were also sensitive and provided important features including the location, size, and depth of ODD and morphology of the optic disc and ODD-associated features such as horizontal hyperreflective lines and peripapillary hyperreflective ovoid mass-like structures (PHOMS), respectively. Color fundus imaging had the lowest sensitivity (82\%). There was good inter-rater reliability for all en face imaging modalities (P \&lt; .0001 for all). CONCLUSIONS: Green-light FAF had the highest sensitivity in diagnosis of ODD, while blue-light FAF and NIR provided more information regarding the severity, location, depth, and size of ODD. In eyes that are negative on green-light FAF, EDI-OCT can be performed and provides the highest-resolution characterization of the entire optic disc to rule out ODD.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.12.023},
	author = {Yan, Yan and Ludwig, Cassie A and Liao, Yaping Joyce}
}
@article {1490441,
	title = {Sphingosine 1-Phosphate Receptor Signaling Establishes AP-1 Gradients to Allow for Retinal Endothelial Cell Specialization},
	journal = {Dev Cell},
	volume = {52},
	number = {6},
	year = {2020},
	month = {2020 Mar 23},
	pages = {779-793.e7},
	abstract = {Transcriptional mechanisms that drive angiogenesis and organotypic vascular endothelial cell specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors (TFs). Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent vascular endothelial (VE)-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this TF. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of β-catenin-dependent genes such as TCF/LEF1 and ZIC3 TFs, transporters, and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 gradient and enabling organotypic endothelial cell specialization of the vascular network.},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2020.01.016},
	author = {Yanagida, Keisuke and Engelbrecht, Eric and Niaudet, Colin and Jung, Bongnam and Gaengel, Konstantin and Holton, Kristina and Swendeman, Steven and Liu, Catherine H and Levesque, Michel V and Kuo, Andrew and Fu, Zhongjie and Smith, Lois E H and Betsholtz, Christer and Hla, Timothy}
}
@article {313191,
	title = {Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization},
	journal = {Proc Natl Acad Sci U S A},
	volume = {111},
	number = {26},
	year = {2014},
	month = {2014 Jul 01},
	pages = {9603-8},
	abstract = {Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)-epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD.},
	keywords = {Animals, Arachidonic Acids, Choroidal Neovascularization, Chromatography, Liquid, Cytochrome P-450 Enzyme System, DNA, Complementary, Enzyme-Linked Immunosorbent Assay, Fatty Acids, Omega-3, Flow Cytometry, Food, Fortified, Immunoblotting, Laser Capture Microdissection, Macular Degeneration, Mice, PPAR gamma, Real-Time Polymerase Chain Reaction, Tandem Mass Spectrometry},
	issn = {1091-6490},
	doi = {10.1073/pnas.1401191111},
	author = {Yanai, Ryoji and Mulki, Lama and Hasegawa, Eiichi and Takeuchi, Kimio and Sweigard, Harry and Suzuki, Jun and Gaissert, Philipp and Vavvas, Demetrios G and Sonoda, Koh-Hei and Rothe, Michael and Schunck, Wolf-Hagen and Miller, Joan W and Connor, Kip M}
}
@article {1364574,
	title = {Complement involvement in neovascular ocular diseases},
	journal = {Adv Exp Med Biol},
	volume = {946},
	year = {2012},
	month = {2012},
	pages = {161-83},
	abstract = {Pathological neovascularization (NV) is a hallmark of late stage neovascular age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinopathy of prematurity (ROP). There is accumulating evidence that alterations in inflammatory and immune system pathways that arise from genetic differences, injury, and disease can predispose individuals to retinal neovascular eye diseases. Yet the mechanism of disease progression with respect to the complement system in these maladies is not fully understood. Recent studies have implicated the complement system as an emerging player in the etiology of several retinal diseases. We will summarize herein several of the complement system pathways known to be involved in ocular neovascular pathologies. Current treatment for many neovascular eye diseases focuses on suppression of NV with laser ablation, photodynamic therapy, or anti-VEGF angiogenic inhibitors. However, these treatments do not address the underlying cause of many of these diseases. A clear understanding of the cellular and molecular mechanisms could bring a major shift in our approach to disease treatment and prevention.},
	keywords = {Choroidal Neovascularization, Complement System Proteins, Diabetic Retinopathy, Humans, Infant, Newborn, Macular Degeneration, Retinopathy of Prematurity},
	issn = {0065-2598},
	doi = {10.1007/978-1-4614-0106-3_10},
	author = {Yanai, Ryoji and Thanos, Aristomenis and Connor, Kip M}
}
@article {1309950,
	title = {Attenuation of choroidal neovascularization by dietary intake of ω-3 long-chain polyunsaturated fatty acids and lutein in mice},
	journal = {PLoS One},
	volume = {13},
	number = {4},
	year = {2018},
	month = {2018},
	pages = {e0196037},
	abstract = {Dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and lutein each protect against age-related macular degeneration (AMD). We here examined the effects of ω-3 LCPUFAs and lutein supplementation in a mouse model of AMD. Mice were assigned to four groups: (1) a control group fed an ω-3 LCPUFA-free diet, (2) a lutein group fed an ω-3 LCPUFA-free diet with oral administration of lutein, (3) an ω-3 group fed an ω-3 LCPUFA-supplemented diet, and (4) an ω-3 + lutein group fed an ω-3 LCPUFA-supplemented diet with oral administration of lutein. Mice were fed the defined diets beginning 2 weeks before, and received lutein with an oral gavage needle beginning 1 week before, induction of choroidal neovascularization (CNV) by laser photocoagulation. The area of CNV measured in choroidal flat-mount preparations was significantly reduced in mice fed ω-3 LCPUFAs or lutein compared with those in the control group, and it was reduced in an additive manner in those receiving both ω-3 LCPUFAs and lutein. The concentrations of various inflammatory mediators in the retina or choroid were reduced in mice fed ω-3 LCPUFAs or lutein, but no additive effect was apparent. The generation of reactive oxygen species (ROS) in chorioretinal lesions revealed by dihydroethidium staining as well as the expression of NADPH oxidase 4 (Nox4) in the retina revealed by immunohistofluorescence and immunoblot analyses were attenuated by ω-3 LCPUFAs and lutein in a synergistic manner. Our results thus show that dietary intake of ω-3 LCPUFAs and lutein attenuated CNV in an additive manner and in association with suppression of inflammatory mediator production, ROS generation, and Nox4 expression. Dietary supplementation with both ω-3 LCPUFAs and lutein warrants further study as a means to protect against AMD.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0196037},
	author = {Yanai, Ryoji and Chen, Shang and Uchi, Sho-Hei and Nanri, Tomoaki and Connor, Kip M and Kimura, Kazuhiro}
}
@article {726226,
	title = {Rescue of Glaucomatous Neurodegeneration by Differentially Modulating Neuronal Endoplasmic Reticulum Stress Molecules.},
	journal = {J Neurosci},
	volume = {36},
	number = {21},
	year = {2016},
	month = {2016 May 25},
	pages = {5891-903},
	abstract = {UNLABELLED: Axon injury is an early event in neurodegenerative diseases that often leads to retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. The connection of these two obviously sequential degenerative events, however, is elusive. Deciphering the upstream signals that trigger the neurodegeneration cascades in both neuronal soma and axon would be a key step toward developing the effective neuroprotectants that are greatly needed in the clinic. We showed previously that optic nerve injury-induced neuronal endoplasmic reticulum (ER) stress plays an important role in retinal ganglion cell (RGC) death. Using two in vivo mouse models of optic neuropathies (traumatic optic nerve injury and glaucoma) and adeno-associated virus-mediated RGC-specific gene targeting, we now show that differential manipulation of unfolded protein response pathways in opposite directions-inhibition of eukaryotic translation initiation factor 2α-C/EBP homologous protein and activation of X-box binding protein 1-promotes both RGC axons and somata survival and preserves visual function. Our results indicate that axon injury-induced neuronal ER stress plays an important role in both axon degeneration and neuron soma death. Neuronal ER stress is therefore a promising therapeutic target for glaucoma and potentially other types of neurodegeneration. SIGNIFICANCE STATEMENT: Neuron soma and axon degeneration have distinct molecular mechanisms although they are clearly connected after axon injury. We previously demonstrated that axon injury induces neuronal endoplasmic reticulum (ER) stress and that manipulation of ER stress molecules synergistically promotes neuron cell body survival. Here we investigated the possibility that ER stress also plays a role in axon degeneration and whether ER stress modulation preserves neuronal function in neurodegenerative diseases. Our results suggest that neuronal ER stress is a general mechanism of degeneration for both neuronal cell body and axon, and that therapeutic targeting of ER stress produces significant functional recovery.},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.3709-15.2016},
	author = {Yang, Liu and Li, Shaohua and Miao, Linqing and Huang, Haoliang and Liang, Feisi and Teng, Xiuyin and Xu, Lin and Wang, Qizhao and Xiao, Weidong and Ridder, William H and Ferguson, Toby A and Chen, Dong Feng and Kaufman, Randal J and Hu, Yang}
}
@article {1632283,
	title = {Hyperintensities of middle frontal gyrus in patients with diabetic optic neuropathy: a dynamic amplitude of low-frequency fluctuation study},
	journal = {Aging (Albany NY)},
	volume = {14},
	number = {3},
	year = {2022},
	month = {2022 Feb 04},
	pages = {1336-1350},
	abstract = {Diabetic optic neuropathy (DON) is a diverse complication of diabetes and its pathogenesis has not been fully elucidated. The purpose of this study was to explore dynamic cerebral activity changes in DON patients using dynamic amplitude of low-frequency fluctuation (dALFF). In total, 22 DON patients and 22 healthy controls were enrolled. The dALFF approach was used in all participants to investigate dynamic intrinsic brain activity differences between the two groups. Compared with HCs, DON patients exhibited significantly increased dALFF variability in the right middle frontal gyrus (P \&lt; 0.01). Conversely, DON patients exhibited obviously decreased dALFF variability in the right precuneus (P \&lt; 0.01). We also found that there were significant negative correlations between HADS scores and dALFF values of the right middle frontal gyrus in the DON patients (r = -0.6404, P \&lt;0.01 for anxiety and r = -0.6346, P \&lt;0.01 for depression; HADS, Hospital Anxiety and Depression Scale). Abnormal variability of dALFF was observed in specific areas of the cerebrum in DON patients, which may contribute to distinguishing patients with DON from HCs and a better understanding of DON, hyperintensities of right middle frontal gyrus may be potential diagnostic marker for DON.},
	issn = {1945-4589},
	doi = {10.18632/aging.203877},
	author = {Yang, Lin and Xiao, Ang and Li, Qiu-Yu and Zhong, Hui-Feng and Su, Ting and Shi, Wen-Qing and Ying, Ping and Liang, Rong-Bin and Xu, San-Hua and Shao, Yi and Zhou, Qiong}
}
@article {1522718,
	title = {RvE1 uses the LTB receptor BLT1 to increase [Ca] and stimulate mucin secretion in cultured rat and human conjunctival goblet cells},
	journal = {Ocul Surf},
	volume = {18},
	number = {3},
	year = {2020},
	month = {2020 07},
	pages = {470-482},
	abstract = {PURPOSE: Specialized pro-resolving lipid mediator resolvin (Rv) E1 stimulates secretion including mucins from conjunctival goblet cells. RvE1 can use both its ChemR23 receptor and the LTB receptor BLT1 to increase [Ca]. The purpose of this study was to determine the expression of ChemR23 and BLT1 and receptors on conjunctival goblet cells and the respective roles these two receptors play in goblet cell responses to RvE1. METHODS: Goblet cells were cultured from male rat or human conjunctiva from both sexes. Western blotting analysis, reverse transcription PCR and immunofluorescence microscopy were used to demonstrate the expression of ChemR23 and BLT1 in conjunctival goblet cells. High molecular weight glycoprotein secretion was determined using an enzyme-linked lectin assay. Signaling pathways were studied by measuring the increase in [Ca] using fura 2/AM. RESULTS: ChemR23 and BLT1 and receptors were present on both rat and human conjunctival goblet cells. The BLT1 inhibitors LY293111 and U75302 significantly blocked RvE1-and LTB-stimulated [Ca] increase. RvE1-and LTB-stimulated [Ca] and secretion increases were blocked by BLT1-targeted siRNA. RvE1-stimulated [Ca] and secretion increases were also blocked by ChemR23-targeted siRNA. Addition of RvE1 2\&nbsp;min before or simultaneously with LTB desensitized the LTB [Ca] response. Addition of RvE1 and LTB simultaneously caused secretion that was decreased compared to either response alone. CONCLUSION: RvE1, in addition to the ChemR23 receptor, uses the BLT1 receptor to increase [Ca] and stimulate secretion in both rat and human cultured conjunctival goblet cells.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2020.04.011},
	author = {Yang, Menglu and Lippestad, Marit and Hodges, Robin R and Fj{\ae}rvoll, Haakon K and Fj{\ae}rvoll, Ketil A and Bair, Jeffery A and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1653592,
	title = {Sex-based differences in conjunctival goblet cell responses to pro-inflammatory and pro-resolving mediators},
	journal = {Sci Rep},
	volume = {12},
	number = {1},
	year = {2022},
	month = {2022 Sep 29},
	pages = {16305},
	abstract = {Many conjunctival inflammatory diseases differ between the sexes and altered conjunctival goblet cells (CGCs) response is often involved. Inflammation is initiated by the release of pro-inflammatory mediators and terminated by the biosynthesis of specialized pro-resolution mediators (SPMs). Herein, we determined the sex-based difference in the responses of CGCs to inflammatory stimuli or pro-resolving lipid SPMs and their interaction with sex hormones. GCs were cultured from pieces of human conjunctiva in RPMI media. CGCs were transferred 24\&nbsp;h before the start of experiments to phenol red-free and FBS-free media to minimize exogenous hormones. RT-PCR, immunofluorescence microscopy (IF), and Western Blot (WB) were performed to determine the presence of sex hormone receptors. Cellular response to pro-inflammatory stimuli or SPMs was studied by measuring the increase in intracellular [Ca2+] ([Ca2+]i) using fura 2/AM microscopy. Use of RT-PCR demonstrated estrogen receptor (ER) α in 4/5 males and 3/3 females; ERβ in 2/4 males and 2/3 females; and androgen receptors (AR) in 3/3 male and 3/3 female CGCs. Positive immunoreactivity by IF and protein expression by WB was detected using antibodies for the ERα and ERβ in 3/3 males and 3/3 females, while AR were only present in males. Significantly different Ca2+ responses between sexes were found with carbachol only at 10-3\&nbsp;M, but not with histamine or leukotriene (LT) B4 at any concentration used. Incubation with dihydrotestosterone (DHT), estrone (E1), or estradiol (E2) at 10-7\&nbsp;M for 30\&nbsp;min significantly inhibited the LTB4-stimulated [Ca2+]i increase in male and female CGCs. Incubation with DHT, E1, and E2 overnight significantly inhibited the LTB4 response in females, while DHT and E2 significantly inhibited the LTB4 response in males. The SPM lipoxin A4 (LXA4) (10-9-10-8\&nbsp;M), but not the resolvins D1 or D2, induced an [Ca2+]i increase that was significantly higher in males compared to females. We conclude that male and female CGCs showed differences in the expression of sex hormone receptors. Treatment with sex hormones altered pro-inflammatory mediator LTB4-induced response. Males compared to females have a higher response to the ω-6-fatty acid derived SPM LXA4, indicating males may terminate inflammation in conjunctival goblet cells faster than females.},
	issn = {2045-2322},
	doi = {10.1038/s41598-022-20177-9},
	author = {Yang, Menglu and Fj{\ae}rvoll, Haakon K and Fj{\ae}rvoll, Ketil A and Wang, Nicholas H and Utheim, Tor P and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1511472,
	title = {ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface},
	journal = {J Biol Chem},
	volume = {295},
	number = {19},
	year = {2020},
	month = {2020 May 08},
	pages = {6641-6651},
	abstract = {Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily -glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte-EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.},
	issn = {1083-351X},
	doi = {10.1074/jbc.RA119.011192},
	author = {Yang, Jinling and LeBlanc, Michelle E and Cano, Issahy and Saez-Torres, Kahira L and Saint-Geniez, Magali and Ng, Yin-Shan and D{\textquoteright}Amore, Patricia A}
}
@article {1517214,
	title = {PDGFRβ plays an essential role in patient vitreous-stimulated contraction of retinal pigment epithelial cells from epiretinal membranes},
	journal = {Exp Eye Res},
	volume = {197},
	year = {2020},
	month = {2020 Aug},
	pages = {108116},
	abstract = {Platelet-derived growth factor (PDGF) is associated with clinical proliferative vitreoretinopathy (PVR), which is characterized by formation of sub- or epi-retinal membranes that consist of cells including retinal pigment epithelial （RPE） cells and extracellular matrix. RPE cells play an important role in PVR pathogenesis. Previous findings indicated that PDGF receptor (PDGFR)α was essential in experimental PVR induced by fibroblasts. In RPE cells derived from epiretinal membranes from patients with PVR (RPEMs)， Akt was activated by PDGF-B but not PDGF-A, which suggested that PDGFRβ was the predominant PDGFR isoform expressed in RPEMs. Indeed, CRISPR/Cas9-mediated depletion of PDGFRβ in RPEMs attenuated patient vitreous-induced Akt activation and cellular responses intrinsic to PVR including cell proliferation, migration, and contraction. We conclude that PDGFRβ appears to be the PVR relevant PDGFR isoform in RPEMs.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2020.108116},
	author = {Yang, Yanhui and Huang, Xionggao and Ma, Gaoen and Cui, Jing and Matsubara, Joanne Aiko and Kazlauskas, Andrius and Zhao, Jun and Wang, Jiantao and Lei, Hetian}
}
@article {1263431,
	title = {AML presenting with a preleukemic episode and acquired heterochromia in a child with macrosomia},
	journal = {Pediatr Blood Cancer},
	volume = {65},
	number = {4},
	year = {2018},
	month = {2018 Apr},
	issn = {1545-5017},
	doi = {10.1002/pbc.26899},
	author = {Yang, Youyang and Kazlas, Melanie and Sharma, Medha and Friedmann, Alison}
}
@article {382231,
	title = {Superior rectus transposition vs medial rectus recession for treatment of esotropic Duane syndrome},
	journal = {JAMA Ophthalmol},
	volume = {132},
	number = {6},
	year = {2014},
	month = {2014 Jun},
	pages = {669-75},
	abstract = {IMPORTANCE: Superior rectus transposition (SRT) with or without medial rectus recession (MRc) has been introduced as an alternative to MRc alone for treatment of esotropic Duane syndrome; however, the effectiveness of these procedures has not been compared previously. OBJECTIVE: To compare the safety and efficacy of MRc and SRT in treatment of Duane syndrome. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of all patients with esotropic Duane syndrome who underwent surgical treatment from January 1, 2006, through December 31, 2012, in a multispecialty, hospital-based pediatric ophthalmology/adult strabismus practice at Boston Children{\textquoteright}s Hospital. Patients in the SRT group underwent SRT with or without MRc; those in the non-SRT group underwent unilateral or bilateral MRc. EXPOSURES: Surgical treatment of esotropic Duane syndrome. MAIN OUTCOMES AND MEASURES: Binocular alignment, ocular ductions, head position, stereopsis, and fundus torsion were recorded before surgery and at the 2-month and final postoperative visits. We also evaluated postoperative drift. RESULTS: The medical record review identified 36 patients who underwent 37 procedures, including 19 in the SRT group (13 SRT + MRc and 6 SRT alone) and 18 in the non-SRT group (11 unilateral MRc and 7 bilateral medial rectus resession). Mean MRc was smaller when performed with SRT (3.3 vs 5.3 mm; P = .004). Although the initial deviation was larger in the SRT group, both groups had a similar improvement in esotropia and head turn. Abduction improved by at least 1 unit in 15 of 19 patients in the SRT group (79\%) vs 5 of 18 in the non-SRT group (28\%). In 24 patients followed up for more than 6 months, mean esotropia decreased from 8.2 to 6.1 prism diopters (Δ) in the SRT group (n = 12) but increased from 7.2 to 10.9Δ in the non-SRT group (n = 12). CONCLUSIONS AND RELEVANCE: The combination of SRT and MRc was more effective than MRc or bilateral medial rectus resession at improving abduction while allowing for a smaller recession to align the eyes and eliminate a compensatory head posture. Although any surgery on the vertical rectus muscles should in theory increase the risk for vertical or torsional complications, to date this theory has not been borne out in our patients. Patients treated with SRT appear to have a reduced likelihood of long-term undercorrection. We therefore recommend SRT with adjustable MRc for treatment of Duane syndrome in patients with larger amounts of esotropia.},
	keywords = {Adolescent, Adult, Child, Cohort Studies, Duane Retraction Syndrome, Esotropia, Eye Movements, Female, Follow-Up Studies, Humans, Male, Oculomotor Muscles, Ophthalmologic Surgical Procedures, Retrospective Studies, Risk Assessment, Treatment Outcome, Vision, Binocular, Young Adult},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2014.358},
	author = {Yang, Shiqiang and MacKinnon, Sarah and Dagi, Linda R and Hunter, David G}
}
@article {1661812,
	title = {Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface},
	journal = {BMC Ophthalmol},
	volume = {22},
	number = {1},
	year = {2022},
	month = {2022 Dec 15},
	pages = {490},
	abstract = {PURPOSE: Transcorneal electrical stimulation (TcES) is increasingly applied as a therapy for preserving and improving vision in retinal neurodegenerative and ischemic disorders. However, a common complaint about TcES is its induction of eye pain and dryness in the clinic, while the mechanisms remain unknown. METHOD: TcES or transpalpebral ES (TpES) was conducted in C57BL6j mice for 14 days. The contralateral eyes were used as non-stimulated controls. Levels of intracellular [Ca2+] ([Ca2+]i) were assessed by Fura-2AM. The conductance resistances of the eye under various ES conditions were measured in vivo by an oscilloscope. RESULTS: Although TcES did not affect tear production, it significantly induced damage to the ocular surface, as revealed by corneal fluorescein staining that was accompanied by significantly decreased mucin (MUC) 4 expression compared to the control. Similar effects of ES were detected in cultured primary corneal epithelium cells, showing decreased MUC4 and ZO-1 levels after the ES in vitro. In addition, TcES decreased secretion of MUC5AC from the conjunctiva in vivo, which was also corroborated in goblet cell cultures, where ES significantly attenuated carbachol-induced [Ca2+]i increase. In contrast to TcES, transpalpebral ES (TpES) did not induce corneal fluorescein staining while significantly increasing tear production. Importantly, the conductive resistance from orbital skin to the TpES was significantly smaller than that from the cornea to the retina in TcES. CONCLUSION: TcES, but not TpES, induces corneal epithelial damage in mice by disrupting mucin homeostasis. TpES thus may represent a safer and more effective ES approach for treating retinal neurodegeneration clinically.},
	keywords = {Animals, Conjunctiva, Dry Eye Syndromes, Electric Stimulation, Fluorescein, Goblet Cells, Homeostasis, Mice, Tears},
	issn = {1471-2415},
	doi = {10.1186/s12886-022-02717-z},
	author = {Yang, Menglu and Lennikov, Anton and Chang, Karen and Ashok, Ajay and Lee, Cherin and Cho, Kin-Sang and Utheim, Tor Paaske and Dartt, Darlene A. and Chen, Dong Feng}
}
@article {1677756,
	title = {Effectiveness of Microinvasive Glaucoma Surgery in the United States: Intelligent Research in Sight Registry Analysis 2013-2019},
	journal = {Ophthalmology},
	volume = {130},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {242-255},
	abstract = {PURPOSE: To evaluate the effectiveness of microinvasive glaucoma surgery (MIGS) with and without concurrent phacoemulsification. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight (IRIS{\textregistered}) Registry who underwent Xen gel stent (ab interno) implantation, endoscopic cyclophotocoagulation (ECP), or goniotomy or canaloplasty from 2013 through\&nbsp;2019. METHODS: Kaplan-Meier survival analysis was used to assess reoperation rates. We defined reoperation as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine factors predictive of reoperation. MAIN OUTCOME MEASURES: Reoperation rate, mean intraocular pressure (IOP) and visual acuity (VA), postoperative complications, predictors of reoperation, and reoperation procedure type. RESULTS: A total of 79 363 eyes from 57 561 patients were included, with 15 118 eyes (19\%) receiving stand-alone MIGS and 64 245 eyes (81\%) receiving MIGS concurrent with phacoemulsification. Overall, patients who underwent MIGS concurrently with phacoemulsification showed lower reoperation rates compared with stand-alone MIGS, most pronounced in ECP and goniotomy or canaloplasty. At postoperative year 2, the cumulative reoperation rate for stand-alone procedures was 15\% for ECP, 24\% for Xen implantation, and 24\% for goniotomy or canaloplasty compared with 3\% for ECP, 19\% for Xen implantation, and 6\% for goniotomy or canaloplasty concurrent with phacoemulsification (P \&lt; 0.001 for each stand-alone MIGS vs. MIGS with phacoemulsification). Black race, older age, moderate and severe glaucoma, higher baseline IOP, and glaucoma subtype were associated with higher reoperation risk. Although IOP decreased in all groups, stand-alone MIGS showed a more substantial decrease in mean IOP. Complication rates from MIGS were low overall: 1\% for ECP, 1\% for Xen implantation, and 2\% for goniotomy or canaloplasty. CONCLUSIONS: In current United States clinical practice, MIGS has substantially lower reoperation rates when performed with phacoemulsification, especially for ECP and goniotomy or canaloplasty. Approximately one-sixth of patients undergoing stand-alone ECP and one-quarter of patients undergoing stand-alone Xen implantation or goniotomy or canaloplasty require reoperation by 2 years. Black race, diagnosis coding of moderate to severe glaucoma, and higher baseline IOP were associated with higher risk of reoperation after MIGS procedures. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
	keywords = {Cataract Extraction, Glaucoma, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Retrospective Studies, Treatment Outcome},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.10.021},
	author = {Yang, Shuang-An and Ciociola, Elizabeth C and Mitchell, William and Hall, Nathan and Lorch, Alice C and Miller, Joan W and Friedman, David S and Boland, Michael V and Tobias Elze and Zebardast, Nazlee and IRIS{\textregistered} Registry Analytic Center Consortium}
}
@article {1762006,
	title = {Genomic DNA activates the AIM2 inflammasome and STING pathways to induce inflammation in lacrimal gland myoepithelial cells},
	journal = {Ocul Surf},
	year = {2023},
	month = {2023 Sep 26},
	abstract = {PURPOSE: Primary Sj{\"o}gren{\textquoteright}s syndrome (pSS) is an autoimmune disease that mainly attacks the lacrimal glands causing severe aqueous-deficient dry eye. Clinical evidence indicates the DNA sensing mechanism in the pathogenesis of pSS. The purpose of the present study is to determine the pro-inflammatory effect of self-genomic DNA (gDNA) on myoepithelial cells (MECs), which along with acinar and ductal cells is a major cell type of the lacrimal gland. METHOD: MECs primary culture was acquired from female C57BL6J mice. Genomic DNA was extracted from the spleen of the same animal. The MECs were challenged with self-gDNA. The cytokine secretion was detected using supernatant by enzyme-linked immunosorbent assay (ELISA). The activation of inflammasomes was determined using FAM-FLICA. Cryosections of NOD.B10.H2b mouse model of pSS were obtained for immunofluorescence microscopy (IF), with Balb/C as control. RESULT: Treatment with gDNA activated AIM2 inflammasome assembly and function, leading to secretion of interleukin (IL)-1β and IL-18 in MECs. The stimulation of IL-1β secretion by gDNA appeared to be solely at the post-translational level, whereas IL-18 secretion was a combination of increased protein synthesis and post-translational modification. Genomic DNA also induced the activation of STimulators of INterferon Genes (STING), which correlated to the activation of STING in the lacrimal gland from the NOD.B10.H2b mouse. STING activation led to the secretion of IFN-β via Nuclear Factor-κB (NF-κB). The IFN-β further enhances the secretion of IL-1β. The contractility of MECs was disabled by treatment with gDNA or poly AnT, independent of the level of intracellular [Ca2+]. CONCLUSION: Self-gDNA induces a proinflammatory response in lacrimal gland MECs by activating both the AIM2 inflammasome and STING and thus may contribute to the pathogenesis of pSS.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2023.09.012},
	author = {Yang, Menglu and Delcroix, Vanessa and Lennikov, Anton and Wang, Nicholas and Makarenkova, Helen P and Dartt, Darlene A.}
}
@article {1603864,
	title = {Usage Patterns of Minimally Invasive Glaucoma Surgery (MIGS) Differ by Glaucoma Type: IRIS Registry Analysis 2013-2018},
	journal = {Ophthalmic Epidemiol},
	year = {2021},
	month = {2021 Jul 26},
	pages = {1-9},
	abstract = {Purpose: To examine patterns of standard (trabeculectomy or glaucoma drainage devices, GDDs) vs novel (minimally invasive glaucoma surgery, MIGS) surgical techniques in the US.Methods: We used the American Academy of Ophthalmology (AAO) IRIS{\textregistered} Registry (Intelligent Research in Sight) queried between 2013 and 2018 (inclusive) to calculate the cumulative proportion of stand-alone, concurrent (same day) or sequential (subsequent day) glaucoma surgical techniques performed in each glaucoma diagnosis type. Secondary analyses of adjusted proportions of concurrent and sequential surgeries stratified by glaucoma diagnosis were also performed.Results: Of 203,146 eyes receiving glaucoma surgeries, open angle glaucoma (OAG) was most likely to undergo all types of intervention. The iStent was the most commonly performed MIGS, primarily for those with normal tension glaucoma (NTG) or OAG (p \&lt;\&nbsp;.001). Conversely, GDD was the most commonly performed procedure in secondary glaucoma or other (specified) glaucoma (p \&lt;\&nbsp;.001). ECP and iStent were the most common concurrent procedures performed; most often for OAG and NTG (p \&lt;\&nbsp;.001). After an initial standard surgery, most eyes underwent recurrent standard interventions (90.3\%). ECP was the most common MIGS performed after an initial standard surgery; particularly in primary angle-closure (PACG) and secondary glaucoma eyes (p \&lt;\&nbsp;.001).Conclusion: Glaucoma type may influence the choice of glaucoma procedures and the decision to perform concurrent as well sequential surgical procedures. Given the poorly understood long term safety and effectiveness of MIGS, and with substantially increasing use of MIGS procedures in recent years, future studies comparing their safety and effectiveness vs standard interventions, for a variety of glaucoma types, is needed.},
	issn = {1744-5086},
	doi = {10.1080/09286586.2021.1955391},
	author = {Yang, Shuang-An and Mitchell, William G and Hall, Nathan and Tobias Elze and Miller, Joan W and Lorch, Alice C and Zebardast, Nazlee}
}
@article {1589747,
	title = {Trends and Usage Patterns of Minimally Invasive Glaucoma Surgery in the United States: IRIS{\textregistered} Registry Analysis 2013-2018},
	journal = {Ophthalmol Glaucoma},
	volume = {4},
	number = {6},
	year = {2021},
	month = {2021 Nov-Dec},
	pages = {558-568},
	abstract = {PURPOSE: Understanding trends and patterns in the use of minimally invasive glaucoma surgery (MIGS) and patient profiles undergoing each procedure is important given their relative expense and unknown long-term safety and effectiveness. DESIGN: Retrospective analysis. PARTICIPANTS: Minimally invasive glaucoma surgeries and standard glaucoma surgeries recorded in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS{\textregistered}) Registry. METHODS: We used the data from IRIS Registry between 2013 and 2018 (inclusive) to measure the annual number of MIGS and standard surgical techniques (trabeculectomy or glaucoma drainage device [GDD] placement) performed in the United States, stratified by demographic characteristics. Secondary analyses of concurrent surgeries and of subsequent surgeries for MIGS and standard surgical technique also were conducted. MAIN OUTCOME MEASURES: Trends and sociodemographic characteristics of MIGS use in the United States. RESULTS: Two hundred three thousand three hundred thirty-two eyes and 232 537 unique procedures had associated, documented International Statistical Classification of Diseases and Related Health Problems (ICD), Ninth or Tenth Revision, codes for glaucoma and were included in final analyses. Among eyes with documented glaucoma diagnoses, a substantial increase in annual MIGS procedures occurred over the study period (from 7586 in 2013 to 39 677) and a smaller decrease in standard glaucoma procedures (from 16 215 to 13 701). The proportion of iStent procedures almost tripled during the study period (from 14\% to 40\%), and by 2017 accounted for almost half (43.7\%) of all glaucoma surgeries in the United States. Twenty-one thousand twenty-five of all eyes (10.3\%) underwent multiple procedures: 7638 (36.3\%) on the same day and 13 387 (63.7\%) on subsequent days. Endocyclophotocoagulation and iStent placement were the most common concurrent procedures (55.4\% of all concurrent procedures). Trabeculectomy and GDD placement were most commonly followed by another standard glaucoma surgery, but when followed by sequential MIGS, endocyclophotocoagulation and goniotomy were the most common procedures performed (33.0\% and 21.9\%, respectively). CONCLUSIONS: A significant increase in MIGS use occurred over the recent 6-year period, despite limited evidence of their long-term safety or effectiveness, highlighting the need for trials comparing safety and outcomes of novel MIGS versus traditional surgical treatments for glaucoma.},
	issn = {2589-4196},
	doi = {10.1016/j.ogla.2021.03.012},
	author = {Yang, Shuang-An and Mitchell, William and Hall, Nathan and Tobias Elze and Lorch, Alice C and Miller, Joan W and Zebardast, Nazlee and IRIS{\textregistered} Registry Data Analytics Consortium}
}
@article {1573127,
	title = {Comparative influence of differentiation and proliferation on gene expression in human meibomian gland epithelial cells},
	journal = {Exp Eye Res},
	volume = {205},
	year = {2021},
	month = {2021 Apr},
	pages = {108452},
	abstract = {We recently discovered that by changing environmental signals, differentiated immortalized human meibomian gland epithelial cells (IHMGECs) de-differentiate into proliferating cells. We also discovered that following exposure to appropriate stimuli, these proliferative cells re-differentiate into differentiated IHMGECs. We hypothesize that this plasticity of differentiated and proliferative IHMGECs is paralleled by very significant alterations in cellular gene expression. To begin to test this hypothesis, we compared the gene expression patterns of IHMGECs during differentiation and proliferation. IHMGECs were cultured for four days in either differentiating or proliferating media. After four days of culture, cells were processed for the analysis of gene expression by using Illumina BeadChips and bioinformatic software. Our study identified significant differences in the expression of more than 9200 genes in differentiated and proliferative IHMGECs. Differentiation was associated with significant increases in the expression of specific genes (e.g. S100 calcium binding protein P; 7,194,386-fold upregulation) and numerous ontologies (e.g. 83 biological process [bp] ontologies with >=100 genes were upregulated), such as those related to development, transport and lysosomes. Proliferation also led to a significant rise in specific gene expressions (e.g. cathelicidin antimicrobial peptide; 859,100-fold upregulation) and many ontologies (115 biological process [bp] ontologies with >=100 genes were upregulated), with most of the highly significant ontologies related to cell cycle (z scores\&nbsp;\&gt;\&nbsp;13.9). Our findings demonstrate that gene expression in differentiated and proliferative IHMGECs is extremely different. These results may have significant implications for the regeneration of HMGECs and the reversal of MG dropout in MG dysfunction.},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2021.108452},
	author = {Yang, Shan and Kam, Wendy R and Liu, Yang and Ding, Juan and Li, Ying and Sullivan, David A}
}
@article {1517196,
	title = {Resolvin E1 Reduces Leukotriene B4-Induced Intracellular Calcium Increase and Mucin Secretion in Rat Conjunctival Goblet Cells},
	journal = {Am J Pathol},
	volume = {190},
	number = {9},
	year = {2020},
	month = {2020 09},
	pages = {1823-1832},
	abstract = {Leukotriene B4 (LTB4) is a major proinflammatory mediator important in host defense, whereas resolvins (Rvs) are produced during the resolution phase of inflammation. The authors determined the actions of both RvE1 and RvD1 on LTB4-induced responses of goblet cells cultured from rat conjunctiva. The responses measured were an increase in the intracellular [Ca] ([Ca]) and high-molecular-weight glycoprotein secretion. Treatment with RvE1 or RvD1 for 30 minutes significantly blocked the LTB4-induced [Ca] increase. The actions of RvE1 on LTB4-induced [Ca] increase were reversed by siRNA for the RvE1 receptor, and the actions of RvD1 were reversed by an RvD1 receptor inhibitor. The RvE1 and RvD1 block of LTB4-stimulated increase in [Ca] was also reversed by an inhibitory peptide to β-adrenergic receptor kinase. LTB4 and block of the LTB4-stimulated increase in [Ca] by RvE1 and RvD1 were partially mediated by the depletion of intracellular Ca stores. RvE1, but not RvD1, counterregulated the LTB4-induced high-molecular-weight glycoprotein secretion. Thus, both RvE1 and RvD1 receptors directly inhibit LTB4 by phosphorylating the LTB4 receptor using β adrenergic receptor kinase. RvE1 receptor counterregulates the LTB4-induced increase in [Ca] and secretion, whereas RvD1 receptor only counterregulates LTB4-induced [Ca] increase.},
	keywords = {Animals, Calcium, Conjunctiva, Eicosapentaenoic Acid, Goblet Cells, Leukotriene B4, Male, Mucins, Rats, Rats, Sprague-Dawley},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.06.001},
	author = {Yang, Menglu and Bair, Jeffrey A and Hodges, Robin R and Serhan, Charles N and Dartt, Darlene A.}
}
@article {1677841,
	title = {Fractional amplitude of low-frequency fluctuation changes of specific cerebral regions in patients with toothache: A functional magnetic resonance imaging study},
	journal = {Brain Behav},
	volume = {13},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {e2937},
	abstract = {BACKGROUND: Previous studies have indicated that pain-related diseases can result in significant functional alterations in the brain. However, differences in spontaneous brain activity in toothache (TA) patients remain unclear. OBJECTIVE: To investigate altered spontaneous brain activity in patients with TA and its underlying mechanisms using the resting-state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF) technique. METHODS: Twelve patients with TA and 12 non-toothache controls (NTCs) (matched for sex, age, and level of education) were enrolled. Spontaneous cerebral activity variations were investigated using the rsfMRI-fALFF technique in all individuals. The mean fALFF values of the TA patients and NTCs were classified using receiver operating characteristic (ROC) curves. The correlations between fALFF signals of distinct brain regions and clinical manifestations of TA patients were evaluated using Pearson{\textquoteright}s correlation analysis. RESULTS: TA patients showed lower fALFF values in the left superior frontal gyrus, medial; right superior frontal gyrus, dorsolateral; and left median cingulate and paracingulate gyri (LDCG) than the NTCs. Moreover, ROC curve analysis indicated that the area under the curve of each cerebral region studied had high accuracy. Besides, in the TA group, the visual analog scale score was negatively correlated with fALFF signal values of the LDCG (r\&nbsp;=\&nbsp;.962, p\&nbsp;\&lt;\&nbsp;.001). CONCLUSION: Abnormal spontaneous activity was detected in numerous brain regions in patients with TA, which may be valuable for understanding the brain processing mechanism underlying TA. These regional changes in brain activity may serve as effective clinical indicators of TA.},
	keywords = {Brain, Brain Mapping, Correlation of Data, Humans, Magnetic Resonance Imaging, Prefrontal Cortex},
	issn = {2162-3279},
	doi = {10.1002/brb3.2937},
	author = {Yang, Jun and Zeng, Wan-Xin and Cheng, Jun and Kang, Min and Liao, Xu-Lin and Ying, Ping and Ling, Qian and Zou, Jie and Wei, Hong and Wang, Yi-Xin and Su, Ting and Shao, Yi}
}
@article {1664956,
	title = {Loss of epigenetic information as a cause of mammalian aging},
	journal = {Cell},
	volume = {186},
	number = {2},
	year = {2023},
	month = {2023 Jan 19},
	pages = {305-326.e27},
	abstract = {All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.},
	keywords = {Aging, Animals, DNA Methylation, Epigenesis, Genetic, Epigenome, Mammals, Nucleoproteins, Saccharomyces cerevisiae},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2022.12.027},
	author = {Yang, Jae-Hyun and Hayano, Motoshi and Griffin, Patrick T and Amorim, Jo{\~a}o A and Bonkowski, Michael S and Apostolides, John K and Salfati, Elias L and Blanchette, Marco and Munding, Elizabeth M and Bhakta, Mital and Chew, Yap Ching and Guo, Wei and Yang, Xiaojing and Maybury-Lewis, Sun and Tian, Xiao and Ross, Jaime M and Coppotelli, Giuseppe and Meer, Margarita V and Rogers-Hammond, Ryan and Vera, Daniel L and Lu, Yuancheng Ryan and Pippin, Jeffrey W and Creswell, Michael L and Dou, Zhixun and Xu, Caiyue and Mitchell, Sarah J and Das, Abhirup and O{\textquoteright}Connell, Brendan L and Thakur, Sachin and Kane, Alice E and Su, Qiao and Mohri, Yasuaki and Nishimura, Emi K and Schaevitz, Laura and Garg, Neha and Balta, Ana-Maria and Rego, Meghan A and Gregory-Ksander, Meredith and Jakobs, Tatjana C and Zhong, Lei and Wakimoto, Hiroko and El Andari, Jihad and Grimm, Dirk and Mostoslavsky, Raul and Wagers, Amy J and Tsubota, Kazuo and Bonasera, Stephen J and Palmeira, Carlos M and Seidman, Jonathan G and Seidman, Christine E and Wolf, Norman S and Kreiling, Jill A and Sedivy, John M and Murphy, George F and Green, Richard E and Garcia, Benjamin A and Berger, Shelley L and Oberdoerffer, Philipp and Shankland, Stuart J and Gladyshev, Vadim N. and Ksander, Bruce R and Pfenning, Andreas R and Rajman, Luis A and Sinclair, David A}
}
@article {1623374,
	title = {Haptic and optic-haptic junction structural integrity of two 3-piece intraocular lenses},
	journal = {J Cataract Refract Surg},
	volume = {48},
	number = {6},
	year = {2022},
	month = {2022 06 01},
	pages = {743-744},
	keywords = {Haptic Technology, Humans, Lens Implantation, Intraocular, Lenses, Intraocular, Optics and Photonics, Phacoemulsification, Prosthesis Design},
	issn = {1873-4502},
	doi = {10.1097/j.jcrs.0000000000000868},
	author = {Yannuzzi, Nicolas A and Watane, Arjun and Patel, Nimesh A and Townsend, Justin H}
}
@article {669316,
	title = {Orbital Decompression in the Endoscopic Age: The Modified Inferomedial Orbital Strut.},
	journal = {Otolaryngol Head Neck Surg},
	volume = {154},
	number = {5},
	year = {2016},
	month = {2016 May},
	pages = {963-9},
	abstract = {OBJECTIVE: Postoperative diplopia occurs in up to 45\% of patients following orbital decompression for exophthalmos associated with Graves{\textquoteright} orbitopathy. We sought to describe outcomes of our balanced orbital decompression strategy that includes the preservation of a modified inferomedial orbital strut (mIOS). STUDY DESIGN: Case series with chart review. SETTING: Academic medical center. SUBJECTS AND METHODS: A total of 115 consecutive orbital decompressions were performed on 73 patients (42 bilateral) with Graves{\textquoteright} orbitopathy. All patients underwent (1) a balanced decompression technique incorporating an endoscopic medial and external lateral decompression and (2) a mIOS technique with preservation of the anterior half of the inferomedial orbital strut. A periorbital periosteal (orbital) sling was utilized in patients (n = 54) without threatened vision loss, proptosis \&gt;28 mm, or periorbital disruption to prevent prolapse of the medial rectus muscle. RESULTS: Utilization of the mIOS technique with or without a sling did not adversely affect the reduction in proptosis (5.1 mm with sling vs 5.0 mm without sling; P = .85).The incidence of new-onset postoperative diplopia was 17\% (n = 6). The sling was not associated with postoperative diplopia (odds ratio = 0.54, 95\% confidence interval: 0.08-3.40, P = .51), while it was associated with resolution of preexisting diplopia (odds ratio = 6.67, 95\% confidence interval: 1.06-42.06, P = .04). No intraoperative complications occurred, and no patients suffered a decrement in visual acuity. CONCLUSION: Balanced orbital decompression utilizing a mIOS in patients with Graves{\textquoteright} orbitopathy provides a safe and effective reduction in proptosis with a low rate of new-onset diplopia as compared with historical values. Utilization of an orbital sling may be beneficial in reducing postoperative diplopia in select patients.},
	issn = {1097-6817},
	doi = {10.1177/0194599816630722},
	author = {Yao, William C and Sedaghat, Ahmad R and Yadav, Prashant and Fay, Aaron and Metson, Ralph}
}
@article {341646,
	title = {Enhanced differentiation and delivery of mouse retinal progenitor cells using a micropatterned biodegradable thin-film polycaprolactone scaffold.},
	journal = {Tissue Eng Part A},
	year = {2014},
	month = {2014 Dec 17},
	abstract = {The deterioration of retinal tissue in advanced stages of retinitis pigmentosa and age-related macular degeneration and the lack of signaling cues for laminar regeneration are significant challenges highlighting the need for a tissue-engineering approach to retinal repair. In this study, we fabricated a biodegradable thin-film polycaprolactone (PCL) scaffold with varying surface topographies using microfabrication techniques. Mouse retinal progenitor cells (mRPC) cultured on PCL scaffolds exhibited enhanced potential to differentiate towards a photoreceptor fate in comparison to mRPCs cultured on control substrates, suggesting that PCL scaffolds are promising as substrates to guide differentiation of mRPCs towards a photoreceptor fate in vitro prior to transplantation. When co-cultured with the retinal explants of rhodopsin null mice, mRPC/PCL constructs showed increased mRPC integration rates compared to directly applied dissociated mRPCs. Moreover, these mRPC/PCL constructs could be delivered into the sub-retinal space of rhodopsin null mice with minimal disturbance of the host retina. Whether co-cultured with retinal explants or transplanted into the sub-retinal space, newly integrated mRPCs localized to the outer nuclear layer and expressed appropriate markers of photoreceptor fate. Thus, the PCL scaffold provides a platform to guide differentiation and organized deliver of mRPCs as a practical strategy to repair damaged retina.},
	issn = {1937-335X},
	doi = {10.1089/ten.TEA.2013.0720},
	author = {Yao, Jing and Ko, Chi Wan and Baranov, Petr Y and Regatieri, Caio V and Redenti, Stephen and Tucker, Budd A and Mighty, Jason and Tao, Sarah L and Young, Michael J}
}
@article {1282171,
	title = {Postoperative Complications of Pars Plana Vitrectomy for Diabetic Retinal Disease},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Dec 07},
	pages = {1-8},
	abstract = {Despite recent advances in the medical management of diabetic retinal disease, there remain established indications for vitreoretinal surgery in the treatment of severe proliferative diabetic retinopathy. These include non-clearing vitreous hemorrhage and tractional retinal detachment. Advances in surgical instrumentation, technique, and experience have led to improved visual outcomes, as well as a corresponding decrease in the incidence of postoperative complications. However, the presence of systemic and ocular factors in diabetic patients increases the risk of adverse events compared to non-diabetic individuals. This review will focus on the most important postoperative complications following pars plana vitrectomy, with specific considerations for the diabetic patient.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353832},
	author = {Yau, Gary L and Silva, Paolo S and Arrigg, Paul G and Sun, Jennifer K}
}
@article {1661811,
	title = {Cytomegalovirus retinitis and immune recovery uveitis in a pediatric patient with leukemia},
	journal = {J AAPOS},
	volume = {27},
	number = {1},
	year = {2023},
	month = {2023 Feb},
	pages = {52-55},
	abstract = {Immune recovery uveitis (IRU) is an ocular form of immune reconstitution inflammatory syndrome, which is rare in the pediatric population. We report a case of IRU in an 11-year-old girl with a history of cytomegalovirus (CMV) retinitis in the setting of acute leukemia, who developed uveitis, vitritis, retinitis, and vasculitis during immune reconstitution. She was found to have negative CMV antigenemia, and the disease occurred during concurrent systemic antiviral therapy. Anterior chamber tap confirmed the absence of the CMV in the eye, and recurrent blood samples continued to reveal absent CMV viral particles systemically while her lymphocyte count was steadily increasing. The patient responded to oral steroids, leading to resolution of active retinitis. Tapering the steroids caused a mild reactivation of the ocular immune response.},
	keywords = {Antiviral Agents, CD4 Lymphocyte Count, Child, Cytomegalovirus Retinitis, Female, Humans, Leukemia, Uveitis, Vitreous Body},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2022.10.004},
	author = {Yavuz Saricay, Leyla and Baldwin, Grace and Leake, Katelyn and Johnston, Alicia and Shah, Ankoor S and Patel, Nimesh A and Gonzalez, Efren}
}
@article {1667709,
	title = {A case of Aicardi syndrome associated with duplication event of Xp22 including SHOX.},
	journal = {Ophthalmic Genet},
	volume = {44},
	number = {6},
	year = {2023},
	month = {2023 Dec},
	pages = {591-594},
	abstract = {BACKGROUND: Aicardi syndrome is a neurodevelopmental disorder characterized by a triad of partial or complete agenesis of the corpus callosum, infantile spasms, and pathognomonic chorioretinal lacunae. METHODS: Examination, multimodal imaging, and genetic testing were used to guide diagnosis. RESULTS: We report a case of a pediatric patient who was initially diagnosed with refractory infantile spasms. The patient was unresponsive to conventional antiepileptic therapy, and genetic testing with whole exome and mitochondrial genome sequencing could not identify the underlying cause, so vigabatrin was initiated. The ophthalmic examination under anesthesia for vigabatrin toxicity screening revealed chorioretinal atrophy in the retinal periphery of both eyes, with two 3-disc diameter chorioretinal lacunae superotemporal and inferonasal to the optic nerve in the left eye. Given the neuroimaging findings of corpus callosum hypoplasia with polymicrogyria and ocular findings, the patient was diagnosed with Aicardi syndrome. Genetic testing revealed a novel duplication event at the Xp22 locus. CONCLUSIONS: Aicardi syndrome, albeit a rare condition, should always be considered in the differential diagnosis when investigating a female child with refractory seizures in early childhood. Genetic testing may help further our understanding of AIS and the search for a genetic etiology.},
	keywords = {Aicardi Syndrome, Anticonvulsants, Child, Child, Preschool, Female, Humans, Retina, Short Stature Homeobox Protein, Spasms, Infantile, Vigabatrin},
	issn = {1744-5094},
	doi = {10.1080/13816810.2023.2172190},
	author = {Yavuz Saricay, Leyla and Hoyek, Sandra and Ashit Parikh, Ayush and Baldwin, Grace and Bodamer, Olaf A and Gonzalez, Efren and Patel, Nimesh A}
}
@article {1664968,
	title = {Can Nerve Growth Factor (NGF) Be a Treatment Option for Pediatric Eye Diseases?},
	journal = {Semin Ophthalmol},
	volume = {38},
	number = {5},
	year = {2023},
	month = {2023 Jul},
	pages = {427-432},
	abstract = {A critical review of mechanisms of action and pharmacokinetics of nerve growth factor (NGF), including topical administration, and the studies showing the NGF treatment for anterior and posterior segment diseases in adult and pediatric population are summarized in our paper. Nerve growth factor is commonly used for many different ocular conditions in the adult population to promote nerve regeneration or cellular rescue. Clinical trials for recombinant human NGF have also treated several challenging ocular conditions, such as neurotrophic keratopathy, glaucoma, and retinitis pigmentosa with cystoid macular edema. The safety and efficacy of NGF have been demonstrated in pediatric patients as well. This leads us to consider new applications of NGF for the treatment of pediatric eye diseases.},
	keywords = {Administration, Topical, Adult, Child, Corneal Dystrophies, Hereditary, Glaucoma, Humans, Nerve Growth Factor, Retinitis Pigmentosa},
	issn = {1744-5205},
	doi = {10.1080/08820538.2023.2168485},
	author = {Yavuz Saricay, Leyla and Gonzalez Monroy, Jose Efren and Fulton, Anne B}
}
@article {1435426,
	title = {Evaluation of the Ocular Surface Disease Index Questionnaire as a Discriminative Test for Clinical Findings in Dry Eye Disease Patients},
	journal = {Curr Eye Res},
	volume = {44},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {941-947},
	abstract = {: To investigate to what extent the OSDI can be utilized as a discriminative test for clinical findings. : One thousand and ninety patients with dry eye disease (DED) were consecutively included and examined for osmolarity, tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), meibum quality (MQ), and diagnosis of meibomian gland dysfunction (MGD). Receiver-operating characteristic curve (ROC) analysis considering optimum balanced sensitivity and specificity (close to 50\%) was used for assessment. : The present study on more than 1,000 patients indicates that the OSDI in the ROC curve analysis is a poor discriminator of pathological scores for TFBUT <= 5 (AUC = 0.553; = .012) and <=10 s (AUC = 0.608; = .002), OSS >= 3 (AUC = 0.54; = .043), ST <= 5 (AUC = 0.550; = .032) and <=10 mm/5 min (AUC = 0.544; = .016), and ME >= 1 (AUC = 0.594; = \&lt;0.001). Pathological scores for osmolarity \&gt;308 and \&gt;316 mOsm/L, OPI, OSS \&gt; 1, MQ, and MGD could not be discriminated by OSDI ( \&gt; .05). : Cut-off values for the OSDI can be defined to discriminate pathological TFBUT (<=5 and <=10), OSS (>=3), ST (<=5 and <=10) and ME, however, the discriminability was low. Our comprehensive study emphasises the importance of taking both symptoms and signs into account in DED management.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2019.1604972},
	author = {Yazdani, Mazyar and Chen, Xiangjun and Tashbayev, Behzod and Utheim, {\O}ygunn A and R{\ae}der, Sten and Hua, Yanjun and Eidet, Jon R and Stojanovic, Aleksandar and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1333946,
	title = {Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort},
	journal = {Curr Eye Res},
	volume = {43},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {1465-1470},
	abstract = {PURPOSE: To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. METHODS: Patients (n\&nbsp;=\&nbsp;1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15\&nbsp;mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p\&nbsp;<=\&nbsp;0.05). RESULTS: The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). CONCLUSIONS: Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.},
	issn = {1460-2202},
	doi = {10.1080/02713683.2018.1514055},
	author = {Yazdani, Mazyar and Chen, Xiangjun and Tashbayev, Behzod and Utheim, {\O}ygunn A and R{\ae}der, Sten and Lagli, Neil and Stojanovic, Aleksandar and Dartt, Darlene A. and Utheim, Tor P}
}
@article {1688376,
	title = {Giant Cell Arteritis Presenting With Multiple Cranial Neuropathies - Case Report},
	journal = {Neurohospitalist},
	volume = {13},
	number = {2},
	year = {2023},
	month = {2023 Apr},
	pages = {188-191},
	abstract = {Background: Vision loss accounts for most ophthalmic presentations of giant cell arteritis (GCA), but an important minority of patients present with diplopia and other cranial neuropathies. Case study: Here we present the case of an 84-year-old woman with a prior history of multiple cancers who was admitted to our hospital after developing double vision. She was found to have mydriasis, ptosis, and ophthalmoplegia in the right eye (OD) consistent with a combined R CNIII/CNVI neuropathy, as well as highly elevated inflammatory markers. Given her cancer history, the patient was initially worked up for various neoplastic, paraneoplastic, inflammatory, and infectious causes of multiple cranial neuropathies; however, as these results were negative, GCA became a more likely contender as a possible rare cause of multiple cranial neuropathies. The patient underwent temporal artery biopsy which showed pathology consistent with giant cell arteritis, and she was treated with steroids with eventual improvement in ophthalmoplegia and ptosis. Conclusions: This case illustrates the importance of recognizing GCA as a rare possible cause of multiple cranial neuropathies, including the indispensable role of temporal artery biopsy.},
	issn = {1941-8744},
	doi = {10.1177/19418744221139893},
	author = {Ye, Jessica J and Bouffard, Marc A and Brooks, Earllondra and Hung, Yin P and Kimchi, Eyal Y}
}
@article {591246,
	title = {Proteomic Analysis of Embryonic and Young Human Vitreous.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {12},
	year = {2015},
	month = {2015 Nov 1},
	pages = {7036-42},
	abstract = {PURPOSE: The proteomic profile of vitreous from second-trimester human embryos and young adults was characterized using mass spectrometry and analyzed for changes in protein levels that may relate to structural changes occurring during this time. This vitreous proteome was compared to previous reports to confirm proteins already identified and reveal novel ones. METHODS: Vitreous from 17 human embryos aged 14 to 20 weeks gestation (WG) and from a 12-, a 14-, a 15-, and a 28-year-old was individually analyzed using tandem mass spectrometry-based proteomics. Peptide spectral count associations with embryonic age were assessed using a general linear model of fold changes and Spearman{\textquoteright}s rank correlation. Differences between embryonic and young adult vitreous proteomes were also compared. Immunohistochemistry was used to evaluate three proteins in five additional fetal (10-18 WG) human eyes. RESULTS: There were 1217 proteins identified in fetal and young adult human vitreous, 206 after quantile normalization and variance filtering. In embryos, the peptide counts of 37 proteins changed significantly from 14 to 20 WG: 75.7\% increased, 24.3\% decreased. Immunohistochemistry confirmed the absence of clusterin and cadherin in 10 and 14 WG eyes and their presence at 18 WG. Comparing embryonic to young adult vitreous, 47 proteins were significantly higher or lower. A total of 768 proteins not previously identified in the literature are presented. CONCLUSIONS: Proteins previously unreported in the human vitreous were identified. The human vitreous proteome undergoes significant changes during embryogenesis and young adulthood. A number of protein levels change considerably during the second trimester, with the majority decreasing.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-16809},
	author = {Yee, Kenneth M P and Feener, Edward P and Madigan, Michele and Jackson, Nicholas J and Gao, Ben-Bo and Ross-Cisneros, Fred N and Provis, Jan and Aiello, Lloyd Paul and Sadun, Alfredo A and Sebag, J}
}
@article {1623342,
	title = {Wnt Signaling in Inner Blood-Retinal Barrier Maintenance},
	journal = {Int J Mol Sci},
	volume = {22},
	number = {21},
	year = {2021},
	month = {2021 Nov 02},
	abstract = {The retina is a light-sensing ocular tissue that sends information to the brain to enable vision. The blood-retinal barrier (BRB) contributes to maintaining homeostasis in the retinal microenvironment by selectively regulating flux of molecules between systemic circulation and the retina. Maintaining such physiological balance is fundamental to visual function by facilitating the delivery of nutrients and oxygen and for protection from blood-borne toxins. The inner BRB (iBRB), composed mostly of inner retinal vasculature, controls substance exchange mainly via transportation processes between (paracellular) and through (transcellular) the retinal microvascular endothelium. Disruption of iBRB, characterized by retinal edema, is observed in many eye diseases and disturbs the physiological quiescence in the retina{\textquoteright}s extracellular space, resulting in vision loss. Consequently, understanding the mechanisms of iBRB formation, maintenance, and breakdown is pivotal to discovering potential targets to restore function to compromised physiological barriers. These unraveled targets can also inform potential drug delivery strategies across the BRB and the blood-brain barrier into retinas and brain tissues, respectively. This review summarizes mechanistic insights into the development and maintenance of iBRB in health and disease, with a specific focus on the Wnt signaling pathway and its regulatory role in both paracellular and transcellular transport across the retinal vascular endothelium.},
	issn = {1422-0067},
	doi = {10.3390/ijms222111877},
	author = {Yemanyi, Felix and Bora, Kiran and Blomfield, Alexandra K and Wang, Zhongxiao and Chen, Jing}
}
@article {1623351,
	title = {FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro},
	journal = {Biomolecules},
	volume = {11},
	number = {11},
	year = {2021},
	month = {2021 Nov 12},
	abstract = {Corneal fibrosis (or scarring) occurs in response to ocular trauma or infection, and by reducing corneal transparency, it can lead to visual impairment and blindness. Studies highlight important roles for transforming growth factor (TGF)-β1 and -β3 as modulators in corneal wound healing and fibrosis, leading to increased extracellular matrix (ECM) components and expression of α-smooth muscle actin (αSMA), a myofibroblast marker. In this study, human corneal fibroblasts (hCF) were cultured as a monolayer culture (2D) or on poly-transwell membranes to generate corneal stromal constructs (3D) that were treated with TGF-β1, TGF-β3, or TGF-β1 + FAK inhibitor (FAKi). Results show that hCF 3D constructs treated with TGF-β1 or TGF-β3 impart distinct effects on genes involved in wound healing and fibrosis-ITGAV, ITGB1, SRC and ACTA2. Notably, in the 3D construct model, TGF-β1 enhanced αSMA and focal adhesion kinase (FAK) protein expression, whereas TGF-β3 did not. In addition, in both the hCF 2D cell and 3D construct models, we found that TGF-β1 + FAKi attenuated TGF-β1-mediated myofibroblast differentiation, as shown by abrogated αSMA expression. This study concludes that FAK signaling is important for the onset of TGF-β1-mediated myofibroblast differentiation, and FAK inhibition may provide a novel beneficial therapeutic avenue to reduce corneal scarring.},
	issn = {2218-273X},
	doi = {10.3390/biom11111682},
	author = {Yeung, Vincent and Sriram, Sriniwas and Tran, Jennifer A and Guo, Xiaoqing and Hutcheon, Audrey E K and Zieske, James D and Karamichos, Dimitrios and Ciolino, Joseph B}
}
@article {1635636,
	title = {Extracellular Vesicles Secreted by Corneal Myofibroblasts Promote Corneal Epithelial Cell Migration},
	journal = {Int J Mol Sci},
	volume = {23},
	number = {6},
	year = {2022},
	month = {2022 Mar 15},
	abstract = {Corneal epithelial wound healing is a multifaceted process that encompasses cell proliferation, migration, and communication from the corneal stroma. Upon corneal injury, bidirectional crosstalk between the epithelium and stroma via extracellular vesicles (EVs) has been reported. However, the mechanisms by which the EVs from human corneal keratocytes (HCKs), fibroblasts (HCFs), and/or myofibroblasts (HCMs) exert their effects on the corneal epithelium remain unclear. In this study, HCK-, HCF-, and HCM-EVs were isolated and characterized, and human corneal epithelial (HCE) cell migration was assessed in a scratch assay following PKH26-labeled HCK-, HCF-, or HCM-EV treatment. HCE cells proliferative and apoptotic activity following EV treatment was assessed. HCF-/HCM-EVs were enriched for CD63, CD81, ITGAV, and THBS1 compared to HCK-EV. All EVs were negative for GM130 and showed minimal differences in biophysical properties. At the proteomic level, we showed HCM-EV with a log \&amp;gt;two-fold change in CXCL6, CXCL12, MMP1, and MMP2 expression compared to HCK-/HCF-EVs; these proteins are associated with cellular movement pathways. Upon HCM-EV treatment, HCE cell migration, velocity, and proliferation were significantly increased compared to HCK-/HCF-EVs. This study concludes that the HCM-EV protein cargo influences HCE cell migration and proliferation, and understanding these elements may provide a novel therapeutic avenue for corneal wound healing.},
	issn = {1422-0067},
	doi = {10.3390/ijms23063136},
	author = {Yeung, Vincent and Zhang, Tancy C and Yuan, Ling and Parekh, Mohit and Cortinas, John A and Delavogia, Eleni and Hutcheon, Audrey E K and Guo, Xiaoqing and Ciolino, Joseph B}
}
@article {1761826,
	title = {APOE4 impairs the microglial response in Alzheimer{\textquoteright}s disease by inducing TGFβ-mediated checkpoints},
	journal = {Nat Immunol},
	volume = {24},
	number = {11},
	year = {2023},
	month = {2023 Nov},
	pages = {1839-1853},
	abstract = {The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer{\textquoteright}s disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration. Deletion of microglial APOE4 restores the MGnD phenotype associated with neuroprotection in P301S tau transgenic mice and decreases pathology in APP/PS1 mice. MGnD-astrocyte cross-talk associated with β-amyloid (Aβ) plaque encapsulation and clearance are mediated via LGALS3 signaling following microglial APOE4 deletion. In the brains of AD donors carrying the APOE4 allele, we found a sex-dependent reciprocal induction of AD risk factors associated with suppression of MGnD genes in females, including LGALS3, compared to individuals homozygous for the APOE3 allele. Mechanistically, APOE4-mediated induction of ITGB8-transforming growth factor-β (TGFβ) signaling impairs the MGnD response via upregulation of microglial homeostatic checkpoints, including Inpp5d, in mice. Deletion of Inpp5d in microglia restores MGnD-astrocyte cross-talk and facilitates plaque clearance in APP/PS1 mice. We identify the microglial APOE4-ITGB8-TGFβ pathway as a negative regulator of microglial response to AD pathology, and restoring the MGnD phenotype via blocking ITGB8-TGFβ signaling provides a promising therapeutic intervention for AD.},
	keywords = {Alzheimer Disease, Amyloid beta-Peptides, Animals, Apolipoprotein E4, Disease Models, Animal, Female, Galectin 3, Humans, Mice, Mice, Transgenic, Microglia},
	issn = {1529-2916},
	doi = {10.1038/s41590-023-01627-6},
	author = {Yin, Zhuoran and Rosenzweig, Neta and Kleemann, Kilian L and Zhang, Xiaoming and Brand{\~a}o, Wesley and Margeta, Milica A and Schroeder, Caitlin and Sivanathan, Kisha N and Silveira, Sebastian and Gauthier, Christian and Mallah, Dania and Pitts, Kristen M and Durao, Ana and Herron, Shawn and Shorey, Hannah and Cheng, Yiran and Barry, Jen-Li and Krishnan, Rajesh K and Wakelin, Sam and Rhee, Jared and Yung, Anthony and Aronchik, Michael and Wang, Chao and Jain, Nimansha and Bao, Xin and Gerrits, Emma and Brouwer, Nieske and Deik, Amy and Tenen, Daniel G and Ikezu, Tsuneya and Santander, Nicolas G and McKinsey, Gabriel L and Baufeld, Caroline and Sheppard, Dean and Krasemann, Susanne and Nowarski, Roni and Eggen, Bart J L and Clish, Clary and Tanzi, Rudolph E and Madore, Charlotte and Arnold, Thomas D and Holtzman, David M and Butovsky, Oleg}
}
@article {1295886,
	title = {In Vitro and In Vivo Methods for Studying Retinal Ganglion Cell Survival and Optic Nerve Regeneration},
	journal = {Methods Mol Biol},
	volume = {1695},
	year = {2018},
	month = {2018},
	pages = {187-205},
	abstract = {Glaucoma is marked by a progressive degeneration of the optic nerve and delayed loss of retinal ganglion cells (RGCs), the projection neurons of the eye. Because RGCs are not replaced and because surviving RGCs cannot regenerate their axons, the visual loss in glaucoma is largely irreversible. Here, we describe methods to evaluate treatments that may be beneficial for treating glaucoma using in vitro cell culture models (immunopanning to isolate neonatal RGCs, dissociated mature retinal neurons, retinal explants) and in vivo models that test potential treatments or investigate underlying molecular mechanisms in an intact system. Potentially, use of these models can help investigators continue to improve treatments to preserve RGCs and restore visual function in patients with glaucoma.},
	issn = {1940-6029},
	doi = {10.1007/978-1-4939-7407-8_16},
	author = {Yin, Yuqin and Benowitz, Larry I}
}
@article {1709671,
	title = {Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer{\textquoteright}s disease},
	journal = {Nat Neurosci},
	volume = {26},
	number = {7},
	year = {2023},
	month = {2023 Jul},
	pages = {1196-1207},
	abstract = {Microglia play a critical role in brain homeostasis and disease progression. In neurodegenerative conditions, microglia acquire the neurodegenerative phenotype (MGnD), whose function is poorly understood. MicroRNA-155 (miR-155), enriched in immune cells, critically regulates MGnD. However, its role in Alzheimer{\textquoteright}s disease (AD) pathogenesis remains unclear. Here, we report that microglial deletion of miR-155 induces a pre-MGnD activation state via interferon-γ (IFN-γ) signaling, and blocking IFN-γ signaling attenuates MGnD induction and microglial phagocytosis. Single-cell RNA-sequencing analysis of microglia from an AD mouse model identifies Stat1 and Clec2d as pre-MGnD markers. This phenotypic transition enhances amyloid plaque compaction, reduces dystrophic neurites, attenuates plaque-associated synaptic degradation and improves cognition. Our study demonstrates a miR-155-mediated regulatory mechanism of MGnD and the beneficial role of IFN-γ-responsive pre-MGnD in restricting neurodegenerative pathology and preserving cognitive function in an AD mouse model, highlighting miR-155 and IFN-γ as potential therapeutic targets for AD.},
	keywords = {Alzheimer Disease, Amyloid beta-Peptides, Animals, Disease Models, Animal, Interferon-gamma, Mice, Mice, Transgenic, Microglia, MicroRNAs, Plaque, Amyloid, Signal Transduction},
	issn = {1546-1726},
	doi = {10.1038/s41593-023-01355-y},
	author = {Yin, Zhuoran and Herron, Shawn and Silveira, Sebastian and Kleemann, Kilian and Gauthier, Christian and Mallah, Dania and Cheng, Yiran and Margeta, Milica A and Pitts, Kristen M and Barry, Jen-Li and Subramanian, Ayshwarya and Shorey, Hannah and Brandao, Wesley and Durao, Ana and Delpech, Jean-Christophe and Madore, Charlotte and Jedrychowski, Mark and Ajay, Amrendra K and Murugaiyan, Gopal and Hersh, Samuel W and Ikezu, Seiko and Ikezu, Tsuneya and Butovsky, Oleg}
}
@article {1593842,
	title = {Advances in corneal graft rejection},
	journal = {Curr Opin Ophthalmol},
	volume = {32},
	number = {4},
	year = {2021},
	month = {2021 07 01},
	pages = {331-337},
	abstract = {PURPOSE OF REVIEW: Immune rejection after corneal transplantation is a major risk for graft failure. We aim to summarize recent advances in the understanding and management of graft rejection. RECENT FINDINGS: Immune rejection remains the leading cause of graft failure in penetrating keratoplasty (PKP). While ABO blood type and sex match between donor and recipient may reduce rejection, human leucocyte antigens class II matching in a randomized study did not reduce the risk of rejection in high-risk PKP. Compared with PKP, deep anterior lamellar keratoplasty, descemet stripping automated endothelial keratoplasty, and descemet membrane endothelial keratoplasty have lower immune rejection rates of 1.7-13\%, 5-11.4\%, and 1.7-2.8\%, respectively, based on long-term (5 years and more) studies. Whether immune rejection is a major risk factor for graft failure in these lamellar keratoplasties is unclear. While there have not been major advances in the systemic management of graft rejection, topical nonsteroid agents such as tacrolimus and anti-vascular endothelial growth factor have shown promise in high-risk cases. SUMMARY: Immune rejection remains the leading cause of graft failure in PKP. Lamellar keratoplasties have significantly lower rejection rates compared with PKP. The significance of rejection in the failure of lamellar grafts warrants further investigation.},
	keywords = {Corneal Diseases, Corneal Transplantation, Graft Rejection, Graft Survival, Humans, Immunity, Cellular, Risk Factors, Tissue Donors},
	issn = {1531-7021},
	doi = {10.1097/ICU.0000000000000767},
	author = {Yin, Jia}
}
@article {1263436,
	title = {Limbal Stem Cell Transplantation and Complications},
	journal = {Semin Ophthalmol},
	year = {2017},
	month = {2017 Nov 27},
	pages = {1-8},
	abstract = {Corneal epithelial stem cells are adult somatic stem cells located at the limbus and represent the ultimate source of transparent corneal epithelium. When these limbal stem cells become dysfunctional or deficient, limbal stem cell deficiency (LSCD) develops. LSCD is a major cause of corneal scarring and is particularly prevalent in chemical and thermal burns of the ocular surface. LSCD leads to conjunctivalization of the corneal surface, neovascularization, recurrent or persistent epithelial defects, ocular surface inflammation, and scarring that, in turn, lead to decreased vision, pain, and impaired quality of life. Several techniques have been reported for limbal stem cell transplantation (LSCT). We introduce the surgical techniques, examine the success rate, and discuss the postoperative complications of conjunctival limbal autograft (CLAU), cultivated limbal stem cell transplantation (CLET), simple limbal epithelial transplantation (SLET), and limbal allograft, including keratolimbal allografts (KLAL) and living-related conjunctival allograft (LR-CLAL).},
	issn = {1744-5205},
	doi = {10.1080/08820538.2017.1353834},
	author = {Yin, Jia and Jurkunas, Ula}
}
@article {1360127,
	title = {Long-term outcome of using Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) as a drug delivery system for bevacizumab in the treatment of corneal neovascularization},
	journal = {Ocul Surf},
	volume = {17},
	number = {1},
	year = {2019},
	month = {2019 Jan},
	pages = {134-141},
	abstract = {PURPOSE: To report the long-term outcome of Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) for delivery of bevacizumab in the treatment of corneal neovascularization (KNV). METHODS: Retrospective, non-comparative, interventional case series of 13 sequential patients treated for KNV at the BostonSight between 2006 and 2017. In all cases, PROSE treatment was initiated for management of ocular surface disease and patients wore PROSE consistently on a daily wear basis prior to bevacizumab treatment. Patients applied a drop of 1\% preservative free bevacizumab to the reservoir of PROSE device twice daily. Patients continued with daily wear of the device during treatment and afterwards. RESULTS: 13 patients (8 female and mean age of 45 years) are included with a mean follow-up of 5.1 years (range 6 months-11 years). Underlying ocular diagnoses included Stevens-Johnson syndrome (7), ocular chronic graft-versus-host disease (2), corneal transplant (2), contact lens-related corneal ulcer and limbal stem cell deficiency (1), and familial dysautonomia (1). Median duration of bevacizumab use was 6 months (range 3 months-10 years). Twelve cases (92\%) had regression of KNV and 10 cases (77\%) had improved best-corrected visual acuity (BCVA) with treatment. Median BCVA improved from -1.1 (LogMAR) at baseline, to -0.66 at end of bevacizumab treatment, and remained -0.63 at last follow-up (P = 0.047). KNV progressed in one eye after discontinuation of bevacizumab. There were no ophthalmic or systemic complications. CONCLUSIONS: Topical bevacizumab used in PROSE is effective in treating KNV and improving vision. Long-term follow-up reveals durable response and no complications.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.11.008},
	author = {Yin, Jia and Jacobs, Deborah S}
}
@article {1470978,
	title = {Optic nerve regeneration: A long view},
	journal = {Restor Neurol Neurosci},
	year = {2019},
	month = {2019 Oct 08},
	abstract = {The optic nerve conveys information about the outside world from the retina to multiple subcortical relay centers. Until recently, the optic nerve was widely believed to be incapable of re-growing if injured, with dire consequences for victims of traumatic, ischemic, or neurodegenerative diseases of this pathway. Over the past 10-20 years, research from our lab and others has made considerable progress in defining factors that normally suppress axon regeneration and the ability of retinal ganglion cells, the projection neurons of the retina, to survive after nerve injury. Here we describe research from our lab on the role of inflammation-derived growth factors, suppression of inter-cellular signals among diverse retinal cell types, and combinatorial therapies, along with related studies from other labs, that enable animals with optic nerve injury to regenerate damaged retinal axons back to the brain. These studies raise the possibility that vision might one day be restored to people with optic nerve damage.},
	issn = {1878-3627},
	doi = {10.3233/RNN-190960},
	author = {Yin, Yuqin and de Lima, Silmara and Gilbert, Hui-Ya and Hanovice, Nicholas J and Peterson, Sheri L and Sand, Rheanna and Sergeeva, Elena G and Wong, Kimberly A and Xie, Lili and Benowitz, Larry I}
}
@article {1307451,
	title = {Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With Graft-versus-Host Disease},
	journal = {Am J Ophthalmol},
	volume = {190},
	year = {2018},
	month = {2018 Jun},
	pages = {17-23},
	abstract = {PURPOSE: To compare the response of dry eye disease (DED) to treatment with topical steroid in patients with and without graft-vs-host disease (GVHD).

DESIGN: Post hoc analysis of a double-masked, randomized clinical trial.

METHODS: This single-center study included 42 patients with moderate-to-severe DED associated with (n~= 21) or without (n~= 21) chronic GVHD. In each group, patients received either loteprednol etabonate 0.5\% ophthalmic suspension or artificial tears twice daily for 4~weeks. Clinical data, including Ocular Surface Disease Index (OSDI) questionnaire, corneal fluorescein staining (CFS), conjunctival lissamine green staining, tear break-up time (TBUT), and Schirmer test, were evaluated before and after treatment.

RESULTS: There were no significant differences in signs and symptoms of DED between the groups at baseline. In non-GVHD patients receiving loteprednol treatment, the average OSDI score decreased by 34\% from 49.5 {\textpm} 5.9 to 32.6 {\textpm} 4.8 (mean {\textpm} standard error of the mean, P~= .001) and the average CFS score decreased by 41\% from 5.6 {\textpm} 0.6 to 3.3 {\textpm} 0.9 (P~= .02). On the other hand, loteprednol treatment in GVHD patients resulted in minimal change in OSDI (59.2 {\textpm} 6.7 to 61.1 {\textpm} 7.1, 3\% increase, P~= .66) and CFS (5.5 {\textpm} 0.5 to 5.3 {\textpm} 1.1, 4\% decrease, P~= .85) scores. Treatment with artificial tears resulted in 22\% decrease of OSDI (P~= .10) and 32\% decrease of CFS (P~= .02) scores in non-GVHD patients, and had minimal effect in patients with GVHD.

CONCLUSIONS: DED patients with ocular GVHD have a less favorable response to a low-dose topical steroid regimen compared with those without ocular GVHD even with similar baseline disease severity.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2018.03.024},
	author = {Yin, Jia and Kheirkhah, Ahmad and Dohlman, Thomas and Saboo, Ujwala and Dana, Reza}
}
@article {1078841,
	title = {Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK},
	journal = {Oncotarget},
	volume = {8},
	number = {20},
	year = {2017},
	month = {2017 May 16},
	pages = {32794-32806},
	abstract = {Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9. This event was mimicked by expression of the active mutant of AMPKα1 and prevented by the dominant negative AMPKα1. Metformin inhibition of BMP9 signaling is possibly mediated by upregulation of Smurf1, leading to degradation of ALK1. Furthermore, metformin suppressed BMP9-induced angiogenesis in mouse matrigel plug. In addition, laser photocoagulation was employed to evaluate the effect of metformin. The data revealed that metformin significantly reduced choroidal neovascularization to a level comparable to LDN212854, an ALK1 specific inhibitor. In conjunction, metformin diminished expression of ALK1 in endothelium of the lesion area. Collectively, our study for the first time demonstrates that AMPK inhibits ALK1 and associated angiogenesis/neovascularization. This may offer us a new avenue for the treatment of related diseases using clinically used pharmacological AMPK activators like metformin in combination with other strategies to enhance the treatment efficacy or in the case of anti-VEGF resistance.},
	issn = {1949-2553},
	doi = {10.18632/oncotarget.15825},
	author = {Ying, Ying and Ueta, Takashi and Jiang, Shanshan and Lin, Hui and Wang, Yuanyuan and Vavvas, Demetrios and Wen, Rong and Chen, Ye-Guang and Luo, Zhijun}
}
@article {837016,
	title = {Risk Score for Predicting Treatment-Requiring Retinopathy of Prematurity (ROP) in the Telemedicine Approaches to Evaluating Acute-Phase ROP Study.},
	journal = {Ophthalmology},
	volume = {123},
	number = {10},
	year = {2016},
	month = {2016 Oct},
	pages = {2176-82},
	abstract = {PURPOSE: To develop a risk score for predicting treatment-requiring retinopathy of prematurity (TR-ROP) in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study. DESIGN: Second analyses of an observational cohort study. PARTICIPANTS: Infants with birth weight (BW) \&lt;1251 g who had >=1 imaging session by 34 weeks of postmenstrual age (PMA) and >=1 subsequent retinopathy of prematurity (ROP) examination for determining TR-ROP by study-certified ophthalmologists. METHODS: Nonphysician trained readers evaluated wide-field retinal image sets for characteristics of ROP, pre-plus/plus disease, and retinal hemorrhage. Risk score points for predicting TR-ROP were derived from the regression coefficients of significant predictors in a multivariate logistic regression model. MAIN OUTCOME MEASURES: TR-ROP. RESULTS: Eighty-five of 771 infants (11.0\%) developed TR-ROP. In a multivariate model, significant predictors for TR-ROP were gestational age (GA) (odds ratio [OR], 5.7; 95\% confidence interval [CI], 1.7-18.9 for <=25 vs. >=28 weeks), need for respiratory support (OR, 7.0; 95\% CI, 1.3-37.1 for high-frequency oscillatory ventilation vs. no respiratory support), slow weight gain (OR, 2.4; 95\% CI, 1.2-4.6 for weight gain <=12 g/day vs. \&gt;15 g/day), and image findings at the first image session including number of quadrants with pre-plus (OR, 3.8; 95\% CI, 1.5-9.7 for 4 pre-plus quadrants vs. no pre-plus), stage and zone of ROP (OR, 4.7; 95\% CI, 2.1-11.8 for stage 1-2 zone I, OR, 5.9; 95\% CI, 2.1-16.6 for stage 3 zone I vs. no ROP), and presence of blot hemorrhage (OR, 3.1; 95\% CI, 1.4-6.7). Image findings predicted TR-ROP better than GA (area under receiver operating characteristic curve [AUC]\&nbsp;= 0.82 vs. 0.75, P\&nbsp;= 0.03). The risk of TR-ROP steadily increased with higher risk score and predicted TR-ROP well (AUC\&nbsp;= 0.88; 95\% CI, 0.85-0.92). Risk score >=3 points for predicting TR-ROP had a sensitivity of 98.8\%, specificity of 40.1\%, and positive and negative predictive values of 17.0\% and 99.6\%, respectively. CONCLUSIONS: Image characteristics at 34 PMA weeks or earlier independently predict TR-ROP. If externally validated in other infants, risk score, calculated from image findings, GA, weight gain, and respiratory support, enables early identification of infants in need of increased surveillance for TR-ROP.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.06.037},
	author = {Ying, Gui-Shuang and Vanderveen, Deborah and Daniel, Ebenezer and Quinn, Graham E and Baumritter, Agnieshka and Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Cooperative Group}
}
@article {1364575,
	title = {Dorsal midbrain syndrome from a ring-enhancing lesion},
	journal = {Semin Ophthalmol},
	volume = {27},
	number = {3-4},
	year = {2012},
	month = {2012 May-Jul},
	pages = {65-8},
	abstract = {A ring-enhancing lesion is an uncommon cause of a dorsal midbrain syndrome. Here, we describe the case of a 60-year-old man with eye movement and pupillary findings consistent with dorsal midbrain syndrome, and in whom neuroimaging showed a single ring-enhancing lesion in the right midbrain and thalamus. Further investigation revealed a longstanding right groin mass which proved to be a malignant melanoma. His intracranial lesion was presumed to be a metastatic lesion, and treated with stereotactic radiosurgery. We report the patient{\textquoteright}s clinical course, and discuss the diagnosis and management of the solitary midbrain lesion.},
	keywords = {Brain Diseases, Brain Neoplasms, Fatal Outcome, Groin, Humans, Male, Melanoma, Mesencephalon, Middle Aged, Ocular Motility Disorders, Pupil Disorders, Syndrome, Thalamus, Tomography, X-Ray Computed},
	issn = {1744-5205},
	doi = {10.3109/08820538.2012.680645},
	author = {Yiu, Glenn and Lessell, Simmons}
}
@article {1363227,
	title = {Surgical outcomes after epiretinal membrane peeling combined with cataract surgery},
	journal = {Br J Ophthalmol},
	volume = {97},
	number = {9},
	year = {2013},
	month = {2013 Sep},
	pages = {1197-201},
	abstract = {OBJECTIVE: To compare functional and anatomical outcomes after idiopathic epiretinal membrane (ERM) peeling combined with phacoemulsification and intraocular lens implantation versus ERM peeling alone. METHODS: A retrospective, non-randomised comparative case series study was conducted of 81 eyes from 79 patients who underwent ERM peeling at the Beth Israel Deaconess Medical Center between 2001 and 2010. Eyes that underwent combined surgery for ERM and cataracts (group 1) were compared with those that had ERM peeling alone (group 2) with respect to best-corrected visual acuity at 6 months and 1 year after surgery, postoperative central macular thickness (CMT) as measured on optical coherence tomography, and rates of complications, including elevated intraocular pressure (IOP), ERM recurrence and need for reoperation. RESULTS: Mean logMAR visual acuity improved significantly in both groups at 6 months (p\&lt;0.001) and 1 year (p\&lt;0.001) after surgery. There was no statistical difference between the two groups in visual acuity improvement at 6 months (p=0.108) or 1 year (p=0.094). Mean CMT of both groups also significantly decreased after surgery (p=0.002), with no statistical difference in CMT reduction between the two groups, but a trend toward less CMT reduction in group 1 (p=0.061). The rates of complications, including IOP elevation, ERM recurrence and frequency of reoperation, were similar in the two groups, with non-statistical trends toward greater ERM recurrence (p=0.084) and need for reoperation (p=0.096) in those that had combined surgery. CONCLUSIONS: Combined surgery for ERMs and cataracts may potentially be as effective as membrane peeling alone with respect to visual and anatomical outcomes. Further studies are necessary to determine if there may be greater ERM recurrence or need for reoperation after combined surgery.},
	keywords = {Adult, Aged, Aged, 80 and over, Epiretinal Membrane, Female, Humans, Lens Implantation, Intraocular, Male, Middle Aged, Phacoemulsification, Retinal Diseases, Retrospective Studies, Visual Acuity, Young Adult},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2013-303189},
	author = {Yiu, Glenn and Marra, Kyle V and Wagley, Sushant and Krishnan, Sheela and Sandhu, Harpal and Kovacs, Kyle and Kuperwaser, Mark and Arroyo, Jorge G}
}
@article {1445341,
	title = {RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues},
	journal = {Science},
	volume = {364},
	number = {6444},
	year = {2019},
	month = {2019 06 07},
	abstract = {How somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA sequencing data from ~6700 samples across 29 normal tissues revealed multiple somatic variants, demonstrating that macroscopic clones can be found in many normal tissues. We found that sun-exposed skin, esophagus, and lung have a higher mutation burden than other tested tissues, which suggests that environmental factors can promote somatic mosaicism. Mutation burden was associated with both age and tissue-specific cell proliferation rate, highlighting that mutations accumulate over both time and number of cell divisions. Finally, normal tissues were found to harbor mutations in known cancer genes and hotspots. This study provides a broad view of macroscopic clonal expansion in human tissues, thus serving as a foundation for associating clonal expansion with environmental factors, aging, and risk of disease.},
	issn = {1095-9203},
	doi = {10.1126/science.aaw0726},
	author = {Yizhak, Keren and Aguet, Fran{\c c}ois and Kim, Jaegil and Hess, Julian M and K{\"u}bler, Kirsten and Grimsby, Jonna and Frazer, Ruslana and Zhang, Hailei and Haradhvala, Nicholas J and Rosebrock, Daniel and Livitz, Dimitri and Li, Xiao and Arich-Landkof, Eila and Shoresh, Noam and Stewart, Chip and Segr{\`e}, Ayellet V and Branton, Philip A and Polak, Paz and Ardlie, Kristin G and Getz, Gad}
}
@article {1452969,
	title = {Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy},
	journal = {Sci Transl Med},
	volume = {11},
	number = {499},
	year = {2019},
	month = {2019 Jul 03},
	abstract = {The Joslin Medalist Study characterized people affected with type 1 diabetes for 50 years or longer. More than 35\% of these individuals exhibit no to mild diabetic retinopathy (DR), independent of glycemic control, suggesting the presence of endogenous protective factors against DR in a subpopulation of patients. Proteomic analysis of retina and vitreous identified retinol binding protein 3 (RBP3), a retinol transport protein secreted mainly by the photoreceptors, as elevated in Medalist patients protected from advanced DR. Mass spectrometry and protein expression analysis identified an inverse association between vitreous RBP3 concentration and DR severity. Intravitreal injection and photoreceptor-specific overexpression of RBP3 in rodents inhibited the detrimental effects of vascular endothelial growth factor (VEGF). Mechanistically, our results showed that recombinant RBP3 exerted the therapeutic effects by binding and inhibiting VEGF receptor tyrosine phosphorylation. In addition, by binding to glucose transporter 1 (GLUT1) and decreasing glucose uptake, RBP3 blocked the detrimental effects of hyperglycemia in inducing inflammatory cytokines in retinal endothelial and M{\"u}ller cells. Elevated expression of photoreceptor-secreted RBP3 may have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF.},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.aau6627},
	author = {Yokomizo, Hisashi and Maeda, Yasutaka and Park, Kyoungmin and Clermont, Allen C and Hernandez, Sonia L and Fickweiler, Ward and Li, Qian and Wang, Chih-Hao and Paniagua, Samantha M and Simao, Fabricio and Ishikado, Atsushi and Sun, Bei and Wu, I-Hsien and Katagiri, Sayaka and Pober, David M and Tinsley, Liane J and Avery, Robert L and Feener, Edward P and Kern, Timothy S and Keenan, Hillary A and Aiello, Lloyd Paul and Sun, Jennifer K and King, George L}
}
@article {1647872,
	title = {Survey of the American Glaucoma Society Membership on Current Glaucoma Drainage Device Placement and Postoperative Corticosteroid Use},
	journal = {Clin Ophthalmol},
	volume = {16},
	year = {2022},
	month = {2022},
	pages = {2305-2310},
	abstract = {Purpose: To assess practice patterns and opinions of glaucoma specialists regarding glaucoma drainage device tube shunt placement and post-operative anti-inflammatory medication use. We also assess the perceived need for a randomized control trial to compare them. Patients and Methods: An online survey was distributed to a group of glaucoma specialists from the American Glaucoma Society via the American Glaucoma Society forum from April to August 2021. Results: One hundred and twenty-eight responses were included. Ninety percent placed tubes in the anterior chamber. Sixty-one percent reported that evidence suggested the superiority of sulcus tube placement over the anterior chamber, whereas 34\% reported there was not enough evidence to suggest superiority of either in preventing endothelial cell loss. Comparing these techniques for intraocular pressure control, 49\% reported evidence suggested sulcus tube placement superiority whereas 46\% reported there was not enough evidence. Over 40\% of respondents reported that they were either unfamiliar with literature or that there was not enough evidence to support the superiority of difluprednate 0.05\% over prednisolone 1\% for post-operative use in preventing endothelial cell loss and for intraocular pressure control. Ninety percent and 81\% of respondents respectively would benefit from randomized control trials comparing outcomes of anterior chamber vs sulcus tube placement and post-operative corticosteroid usage. Conclusion: Most glaucoma specialists surveyed place glaucoma drainage device tube in the anterior chamber over the sulcus. A randomized control trial to determine optimal tube placement and post-operative anti-inflammatory medication use for preventing endothelial cell loss would change current glaucoma drainage device practice patterns.},
	issn = {1177-5467},
	doi = {10.2147/OPTH.S369673},
	author = {Yonamine, Sean and Ton, Lauren and Rose-Nussbaumer, Jennifer and Ying, Gui-Shuang and Ahmed, Iqbal Ike K and Chen, Teresa C and Weiner, Asher and Gedde, Steven J and Han, Ying}
}
@article {1364577,
	title = {Epidemiology and management of uveal melanoma},
	journal = {Hematol Oncol Clin North Am},
	volume = {26},
	number = {6},
	year = {2012},
	month = {2012 Dec},
	pages = {1169-84},
	abstract = {Uveal melanoma is the most common primary intraocular malignancy in adults. The disease overwhelmingly affects white populations. Other risk factors include fair skin, light iris color, ancestry from northern latitudes, and ocular/oculodermal melanocytosis. Historically, enucleation was the definitive treatment of uveal melanoma, but brachytherapy and proton beam irradiation are now the most commonly used treatment methods. However, there are still no effective therapies against metastatic uveal melanoma, which is almost always fatal. Continued advances in understanding of the molecular mechanisms of uveal melanoma will facilitate the identification of prognostic markers and therapeutic targets.},
	keywords = {Humans, Melanoma, Uveal Neoplasms},
	issn = {1558-1977},
	doi = {10.1016/j.hoc.2012.08.004},
	author = {Yonekawa, Yoshihiro and Kim, Ivana K}
}
@article {280891,
	title = {Leukocoria in a 2-year-old boy.},
	journal = {J Paediatr Child Health},
	volume = {50},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {744},
	issn = {1440-1754},
	doi = {10.1111/jpc.12561},
	author = {Yonekawa, Yoshihiro and Shah, Ankoor S and France, Richard M and Ciarlini, Pedro and VanderVeen, Deborah K}
}
@article {1363231,
	title = {Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration},
	journal = {Am J Ophthalmol},
	volume = {156},
	number = {1},
	year = {2013},
	month = {2013 Jul},
	pages = {29-35.e2},
	abstract = {PURPOSE: To explore the visual and anatomic outcomes of patients with refractory or recurrent neovascular age-related macular degeneration (AMD) who were converted from bevacizumab and/or ranibizumab to aflibercept. DESIGN: Two-center, retrospective chart review. METHODS: Treatment history, visual acuity (VA), and central macular thickness (CMT) on spectral-domain optical coherence tomography were collected. Patients were divided into "refractory" (persistent exudation despite monthly injections) or "recurrent" (exudation suppressed, but requiring frequent injections). RESULTS: One hundred and two eyes of 94 patients were included; 68 were refractory and 34 were recurrent. Eyes received a mean of 20.4 prior bevacizumab/ranibizumab injections and a mean of 3.8 aflibercept injections. Mean follow-up was 18\&nbsp;weeks. Mean VA was 20/50-1 before conversion, 20/50-2 after 1 aflibercept injection (P\&nbsp;= .723), and 20/50+2 after the final injection (P\&nbsp;= .253). Subgroup analysis of refractory and recurrent cases also showed stable VA. Of the refractory cases, mean CMT had improved after 1 injection (P \&lt; .001) and the final injection (P \&lt; .001). Intraretinal (P\&nbsp;\&lt;\&nbsp;.001) and subretinal (P \&lt; .001) fluid decreased after 1 injection, and the mean injection interval was extended from 5.2 to 6.2\&nbsp;weeks (P\&nbsp;= .003). Of the recurrent cases, mean CMT improved after 1 injection (P\&nbsp;\&lt;\&nbsp;.001) and the final injection (P \&lt; .001). Intraretinal (P\&nbsp;= .003) and subretinal (P\&nbsp;= .046) fluid decreased after 1 injection, and the mean injection interval was extended from 7.2 to 9.5\&nbsp;weeks (P\&nbsp;= .001). CONCLUSIONS: Converting patients with chronic neovascular AMD to aflibercept results in stabilized vision and improved anatomic outcomes, while allowing injection intervals to be extended.},
	keywords = {Aged, Aged, 80 and over, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Bevacizumab, Chronic Disease, Drug Substitution, Drug Therapy, Combination, Female, Humans, Intravitreal Injections, Male, Middle Aged, Ranibizumab, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins, Recurrence, Retrospective Studies, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Visual Acuity, Wet Macular Degeneration},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.03.030},
	author = {Yonekawa, Yoshihiro and Andreoli, Christopher and Miller, John B and Loewenstein, John I and Sobrin, Lucia and Eliott, Dean and Vavvas, Demetrios G and Miller, Joan W and Kim, Ivana K}
}
@article {281101,
	title = {Aggressive skull base metastasis from uveal melanoma: a clinicopathologic study},
	journal = {Eur J Ophthalmol},
	volume = {24},
	number = {5},
	year = {2014},
	month = {2014 Sep-Oct},
	pages = {811-3},
	abstract = {PURPOSE: We present the clinical, pathologic, and genetic findings of the first reported case of choroidal melanoma that developed a late recurrence and aggressive metastasis to the skull base without evidence of hepatic involvement. METHODS: Retrospective chart review and clinicopathologic correlation of ocular and brain tissue, including sequencing of BAP1 for mutations. RESULTS: A 55-year-old woman was diagnosed with choroidal melanoma and treated with proton radiotherapy. Six years later, she developed a rapidly growing local recurrence involving the ciliary body and iris. Upon enucleation, histopathology revealed an iris and ciliary body epithelioid melanoma that was contiguous with the previously treated, regressed spindle cell choroidal melanoma. Imaging was initially negative for brain involvement. Two months later, she developed cranial neuropathies and was found to have a large skull base lesion that required surgical debulking for pain palliation. Histopathology confirmed the lesion to be metastatic melanoma. Both ocular and brain tumor specimens were wild-type for BAP1. Throughout her course, she developed no hepatic metastases. CONCLUSIONS: Uveal melanoma may metastasize to the skull base. The present case was characterized by delayed onset and unusual aggressiveness of the metastatic disease, and lack of BAP1 mutation. The unusual course highlights a unique phenotype that may reflect an alternate molecular mechanism for metastatic disease.},
	keywords = {Biomarkers, Tumor, Eye Enucleation, Fatal Outcome, Female, Humans, Magnetic Resonance Imaging, Melanoma, Middle Aged, Proton Therapy, Retrospective Studies, Skull Base Neoplasms, Uveal Neoplasms},
	issn = {1724-6016},
	doi = {10.5301/ejo.5000468},
	author = {Yonekawa, Yoshihiro and Kim, Ivana K and Gragoudas, Evangelos S and Njauw, Ching-Ni J and Tsao, Hensin and Jakobiec, Frederick A and Stacy, Rebecca C}
}
@article {1363228,
	title = {Traumatic macular hole from intentional basketball overinflation},
	journal = {Ophthalmic Surg Lasers Imaging Retina},
	volume = {44},
	number = {3},
	year = {2013},
	month = {2013 May-Jun},
	pages = {303-5},
	abstract = {We report a new mechanism of ocular trauma. A basketball was intentionally overinflated until it exploded, resulting in corneal edema, hyphema, iritis, vitreous hemorrhage, commotio retinae, and a macular hole. The macular hole did not close after observation and subsequent pars plana vitrectomy with posterior hyaloid removal, but a repeat vitrectomy with internal limiting membrane peeling resulted in hole closure. Basketball overinflation to the point of explosion is a potentially blinding practice of which the public and manufacturers should be made aware.},
	keywords = {Adolescent, Basketball, Blast Injuries, Explosions, Eye Injuries, Humans, Male, Retinal Perforations},
	issn = {2325-8179},
	doi = {10.3928/23258160-20130503-20},
	author = {Yonekawa, Yoshihiro and Miller, John B and Turalba, Angela V and Eliott, Dean}
}
@article {726231,
	title = {Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery: An International Multicenter Study.},
	journal = {Ophthalmology},
	volume = {123},
	number = {8},
	year = {2016},
	month = {2016 Aug},
	pages = {1802-8},
	abstract = {PURPOSE: To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. DESIGN: International, multicenter, interventional, retrospective case series. PARTICIPANTS: Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)-defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter-performed in both eyes sequentially during the same anesthesia session. METHODS: Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. MAIN OUTCOME MEASURES: Ocular and systemic adverse events. RESULTS: A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3{\textpm}2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6\%), systemic morbidity placing the child at high anesthesia risk (76.0\%), and residence remote from surgery location (30.2\%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7\% [P \&lt; 0.01]; stage 3, 4.8\%; stage 4A, 44.4\%; stage 4B, 22.4\%; stage 5, 26.4\%), familial exudative vitreoretinopathy (7.0\%), abusive head trauma (4.1\%), persistent fetal vasculature (3.5\%), congenital cataract (1.7\%), posterior capsular opacification (1.7\%), rhegmatogenous retinal detachment (1.7\%), congenital X-linked retinoschisis (1.2\%), Norrie disease (2.3\%), and viral retinitis (1.2\%). Mean surgical time was 143{\textpm}59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P\&nbsp;= 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6\%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203{\textpm}87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6\%) and 1 case of prolonged oxygen desaturation (0.6\%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8\% and 98.0\%, respectively. CONCLUSIONS: This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2016.04.033},
	author = {Yonekawa, Yoshihiro and Wu, Wei-Chi and Kusaka, Shunji and Robinson, Joshua and Tsujioka, Daishi and Kang, Kai B and Shapiro, Michael J and Padhi, Tapas R and Jain, Lubhani and Sears, Jonathan E and Kuriyan, Ajay E and Berrocal, Audina M and Quiram, Polly A and Gerber, Amanda E and Paul Chan, R V and Jonas, Karyn E and Wong, Sui Chien and Patel, C K and Abbey, Ashkan M and Spencer, Rand and Blair, Michael P and Chang, Emmanuel Y and Papakostas, Thanos D and Vavvas, Demetrios G and Sisk, Robert A and Ferrone, Philip J and Henderson, Robert H and Olsen, Karl R and Hartnett, M Elizabeth and Chau, Felix Y and Mukai, Shizuo and Murray, Timothy G and Thomas, Benjamin J and Meza, P Anthony and Drenser, Kimberly A and Trese, Michael T and Capone, Antonio}
}
@article {1078846,
	title = {PROGRESSIVE RETINAL DETACHMENT IN INFANTS WITH RETINOPATHY OF PREMATURITY TREATED WITH INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB},
	journal = {Retina},
	volume = {38},
	number = {6},
	year = {2018},
	month = {2018 Jun},
	pages = {1079-1083},
	abstract = {PURPOSE: Fibrovascular contraction and tractional retinal detachment (TRD) are recognized complications associated with the use of anti-vascular endothelial growth factor agents in vasoproliferative vitreoretinopathies. The authors characterize TRDs that developed after intravitreal bevacizumab or ranibizumab therapy for vascularly active retinopathy of prematurity.

METHODS: This is an international, multicenter, interventional, retrospective, case series. Thirty-five eyes from 23 infants were included. Inclusion required anti-vascular endothelial growth factor treatment of Type 1 retinopathy of prematurity with progression to TRD.

RESULTS: Mean gestational age was 26 {\textpm} 2 weeks, and mean birth weight was 873 {\textpm} 341 g. Mean postmenstrual age on the day of injection was 35 {\textpm} 2 weeks. Retinal detachment was noted a mean of 70 days (median, 34; range, 4-335) after injection. Eleven percent detached within 1 week, 23\% within 2 weeks, and 49\% within 4 weeks. The highest stage of retinopathy of prematurity noted was 4A in 29\%, 4B in 37\%, and 5 in 34\% of eyes. Time to RD negatively correlated with postmenstrual age at the time of injection (Rho = -0.54; P < 0.01). Three TRD configurations were observed: 1) conventional peripheral elevated ridge or volcano-shaped Stage 5 detachment, 2) midperipheral detachment with tight circumferential vectors, and 3) very posterior detachment with prepapillary contraction. Full or partial reattachment was achieved with surgical intervention in 86\% of eyes.

CONCLUSION: Progressive atypical TRD may occur after anti-vascular endothelial growth factor injections for retinopathy of prematurity. The configuration of the detachment varies with the extent of primary retinal vascularization present at the time of treatment.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000001685},
	author = {Yonekawa, Yoshihiro and Wu, Wei-Chi and Nitulescu, Cristina E and Chan, R V Paul and Thanos, Aristomenis and Thomas, Benjamin J and Todorich, Bozho and Drenser, Kimberly A and Trese, Michael T and Capone, Antonio}
}
@article {1363232,
	title = {Congenital glaucoma},
	journal = {J Pediatr},
	volume = {163},
	number = {1},
	year = {2013},
	month = {2013 Jul},
	pages = {301},
	keywords = {Child, Preschool, Glaucoma, Humans, Male},
	issn = {1097-6833},
	doi = {10.1016/j.jpeds.2013.01.067},
	author = {Yonekawa, Yoshihiro and VanderVeen, Deborah K and Shah, Ankoor S}
}
@article {303876,
	title = {Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration.},
	journal = {Cold Spring Harb Perspect Med},
	year = {2014},
	month = {2014 Oct 3},
	abstract = {Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies.},
	issn = {2157-1422},
	doi = {10.1101/cshperspect.a017178},
	author = {Yonekawa, Yoshihiro and Kim, Ivana K}
}
@article {1363229,
	title = {Inferior peripheral nonperfusion in bilateral diffuse uveal melanocytic proliferation},
	journal = {Ophthalmic Surg Lasers Imaging Retina},
	volume = {44},
	number = {2},
	year = {2013},
	month = {2013 Mar-Apr},
	pages = {190-2},
	abstract = {Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic syndrome characterized by cataract, photoreceptor loss and subretinal fluid overlying patchy areas of retinal pigment epithelium atrophy, and a diffusely thickened choroid with focal nodules. We present the case of a 64-year-old woman with a history of endometrial adenocarcinoma who developed BDUMP with bilateral exudative retinal detachments with inferior peripheral retinal ischemia. This new finding of peripheral nonperfusion expands the spectrum of BDUMP.},
	keywords = {Adenocarcinoma, Antineoplastic Agents, Phytogenic, Atrophy, Cell Proliferation, Endometrial Neoplasms, Fatal Outcome, Female, Fluorescein Angiography, Humans, Melanocytes, Middle Aged, Paclitaxel, Paraneoplastic Syndromes, Ocular, Retinal Detachment, Retinal Pigment Epithelium, Tomography, Optical Coherence, Tomography, X-Ray Computed, Uveal Diseases},
	issn = {2325-8179},
	doi = {10.3928/23258160-20130313-11},
	author = {Yonekawa, Yoshihiro and Shildkrot, Yevgeniy and Eliott, Dean}
}
@article {1364576,
	title = {Pseudophakic cystoid macular edema},
	journal = {Curr Opin Ophthalmol},
	volume = {23},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {26-32},
	abstract = {PURPOSE OF REVIEW: Pseudophakic cystoid macular edema (PCME) is a common cause of visual impairment after cataract surgery. This article systematically reviews and discusses the epidemiology, risk factors, diagnosis, and treatment of PCME, with a focus on advances in the past 1-2 years. RECENT FINDINGS: The incidence of PCME has declined with the advent of modern surgical techniques. Optical coherence tomography (OCT) has become an important adjunct to biomicroscopy and fluorescein angiography. PCME prophylaxis with topical nonsteroidal anti-inflammatory drugs remains unproven because long-term visual outcomes and comparative effectiveness studies are lacking. Chronic, refractory CME remains a therapeutic challenge, but investigational therapies with potential include corticosteroid intravitreal injections and implants, and intravitreal anti-vascular endothelial growth factor treatments. Few studies have assessed surgical options. SUMMARY: There is currently a lack of well designed randomized clinical trials to guide the treatment of PCME.},
	keywords = {Cataract Extraction, Humans, Incidence, Lens Implantation, Intraocular, Macular Edema, Pseudophakia, Risk Factors, Vision Disorders},
	issn = {1531-7021},
	doi = {10.1097/ICU.0b013e32834cd5f8},
	author = {Yonekawa, Yoshihiro and Kim, Ivana K}
}
@article {382221,
	title = {Ocular blast injuries in mass-casualty incidents: the marathon bombing in Boston, Massachusetts, and the fertilizer plant explosion in West, Texas},
	journal = {Ophthalmology},
	volume = {121},
	number = {9},
	year = {2014},
	month = {2014 Sep},
	pages = {1670-6.e1},
	abstract = {PURPOSE: To report the ocular injuries sustained by survivors of the April 15, 2013, Boston Marathon bombing and the April 17, 2013, fertilizer plant explosion in West, Texas. DESIGN: Multicenter, cross-sectional, retrospective, comparative case series. PARTICIPANTS: Seventy-two eyes of 36 patients treated at 12 institutions were included in the study. METHODS: Ocular and systemic trauma data were collected from medical records. MAIN OUTCOME MEASURES: Types and severity of ocular and systemic trauma and associations with mechanisms of injury. RESULTS: In the Boston cohort, 164 of 264 casualties were transported to level 1 trauma centers, and 22 (13.4\%) required ophthalmology consultations. In the West cohort, 218 of 263 total casualties were transported to participating centers, of which 14 (6.4\%) required ophthalmology consultations. Boston had significantly shorter mean distances to treating facilities (1.6 miles vs. 53.6 miles; P = 0.004). Overall, rigid eye shields were more likely not to have been provided than to have been provided on the scene (P\&lt;0.001). Isolated upper body and facial wounds were more common in West largely because of shattered windows (75.0\% vs. 13.6\%; P = 0.001), resulting in more open-globe injuries (42.9\% vs. 4.5\%; P = 0.008). Patients in Boston sustained more lower extremity injuries because of the ground-level bomb. Overall, 27.8\% of consultations were called from emergency rooms, whereas the rest occurred afterward. Challenges in logistics and communications were identified. CONCLUSIONS: Ocular injuries are common and potentially blinding in mass-casualty incidents. Systemic and ocular polytrauma is the rule in terrorism, whereas isolated ocular injuries are more common in other calamities. Key lessons learned included educating the public to stay away from windows during disasters, promoting use of rigid eye shields by first responders, the importance of reliable communications, deepening the ophthalmology call algorithm, the significance of visual incapacitation resulting from loss of spectacles, improving the rate of early detection of ocular injuries in emergency departments, and integrating ophthalmology services into trauma teams as well as maintaining a voice in hospital-wide and community-based disaster planning.},
	keywords = {Adult, Blast Injuries, Bombs, Boston, Child, Cross-Sectional Studies, Emergency Medical Services, Explosive Agents, Eye Injuries, Female, Humans, Male, Mass Casualty Incidents, Retrospective Studies, Texas},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2014.04.004},
	author = {Yonekawa, Yoshihiro and Hacker, Henry D and Lehman, Roy E and Beal, Casey J and Veldman, Peter B and Vyas, Neil M and Shah, Ankoor S and Wu, David and Eliott, Dean and Gardiner, Matthew F and Kuperwaser, Mark C and Rosa, Robert H and Ramsey, Jean E and Miller, Joan W and Mazzoli, Robert A and Lawrence, Mary G and Arroyo, Jorge G}
}
@article {1363230,
	title = {Standard fractionation low-dose proton radiotherapy for diffuse choroidal hemangiomas in pediatric Sturge-Weber syndrome},
	journal = {J AAPOS},
	volume = {17},
	number = {3},
	year = {2013},
	month = {2013 Jun},
	pages = {318-22},
	abstract = {Sturge-Weber syndrome is a nonhereditary congenital neurocutaneous syndrome characterized by leptomeningeal angiomatosis, facial nevus flammeus, and diffuse choroidal hemangioma, which when complicated by total retinal detachment, portend a poor prognosis. Management is often limited to salvage external beam irradiation. We present a modified proton therapy technique for young children with total bullous retinal detachments that uses standard fractionation low-dose proton radiotherapy to decrease the risk of radiation complications. Treatment techniques for young children who cannot cooperate with conventional radiation protocols are also described.},
	keywords = {Child, Child, Preschool, Choroid Neoplasms, Dose Fractionation, Hemangioma, Humans, Magnetic Resonance Imaging, Male, Proton Therapy, Retinal Detachment, Sturge-Weber Syndrome, Ultrasonography, Visual Acuity},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2013.01.003},
	author = {Yonekawa, Yoshihiro and MacDonald, Shannon M and Shildkrot, Yevgeniy and Mukai, Shizuo}
}
@article {1460354,
	title = {Corneal Cross-Linking: An Effective Treatment Option for Pellucid Marginal Degeneration},
	journal = {Semin Ophthalmol},
	year = {2019},
	month = {2019 Aug 26},
	pages = {1-6},
	abstract = {: This is the first review article examining literature specific to the use of corneal cross-linking (CXL) to treat pellucid marginal degeneration (PMD). : CXL appears to be an effective treatment that may halt the progression of PMD to stabilize vision. This could postpone or eliminate the need for corneal transplantation in the management of these patients. Furthermore, combining CXL with keratorefractive surgery in a single procedure has been shown to be safe and successful in improving vision in PMD patients. : The data reported in literature is limited at this time, consisting mostly of retrospective studies with short term follow up. Further research is needed to evaluate refractive effects of combined CXL and excimer laser procedures.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2019.1659832},
	author = {Yong, J J and Hatch, K M}
}
@article {1363234,
	title = {Secondary tarsoconjunctival graft: a modification to the Cutler-Beard procedure},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {29},
	number = {3},
	year = {2013},
	month = {2013 May-Jun},
	pages = {227-30},
	abstract = {PURPOSE: The Cutler-Beard procedure is a commonly used technique to reconstruct large upper eyelid defects. Eyelid retraction and entropion are common complications. To prevent these problems, the authors modified the traditional Cutler-Beard procedure with secondary placement of an autologous tarsoconjunctival graft. METHODS: This is a retrospective review of 2 patients with large upper eyelid defects necessitating upper eyelid reconstruction. The initial stage is unaltered. At the time of flap division, a tarsoconjunctival graft from the contralateral upper eyelid is sutured to the posterior surface of the newly constructed upper eyelid. Two patients underwent this procedure, and follow up was 4 and 23 months, respectively. Patients developed no postoperative complications, including entropion or retraction. CONCLUSIONS: This modification to the Cutler-Beard operation is a technically simple procedure that can restore a more anatomically correct eyelid and can prevent subsequent entropion or retraction. This technique is unique, offering 3 major advances: first, placing the graft at the second surgical stage; second, replacing the tarsus and conjunctiva with like tissue; and third, preserving a lip of conjunctiva to cover the edge of the newly reconstructed upper eyelid.},
	keywords = {Adult, Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Conjunctiva, Eyelid Diseases, Eyelid Neoplasms, Eyelids, Humans, Male, Middle Aged, Ophthalmologic Surgical Procedures, Reconstructive Surgical Procedures, Retrospective Studies, Skin Neoplasms},
	issn = {1537-2677},
	doi = {10.1097/IOP.0b013e3182831c84},
	author = {Yoon, Michael K and McCulley, Timothy J}
}
@article {1589762,
	title = {Case 12-2021: A 78-Year-Old Man with a Rash on the Scalp and Face},
	journal = {N Engl J Med},
	volume = {384},
	number = {16},
	year = {2021},
	month = {2021 Apr 22},
	pages = {1553-1562},
	keywords = {Aged, Blepharoptosis, Diagnosis, Differential, Exanthema, Face, Fever, Head, Humans, Male, Scalp, Tomography, X-Ray Computed, Varicella Zoster Virus Infection},
	issn = {1533-4406},
	doi = {10.1056/NEJMcpc2100276},
	author = {Yoon, Michael K and Kelly, Hillary R and Freitag, Suzanne K and Marneros, Alexander G and Barshak, Miriam B and Brackett, Diane G}
}
@article {1363235,
	title = {Skull thickening, paranasal sinus expansion, and sella turcica shrinkage from chronic intracranial hypotension},
	journal = {J Neurosurg Pediatr},
	volume = {11},
	number = {6},
	year = {2013},
	month = {2013 Jun},
	pages = {667-72},
	abstract = {In children or young adults, the morphology of the skull can be altered by excessive drainage of CSF following placement of a ventriculoperitoneal (VP) shunt. In Sunken Eyes, Sagging Brain Syndrome, gradual enlargement of the orbital cavity occurs from low or negative intracranial pressure (ICP), leading to progressive bilateral enophthalmos. The authors report several heretofore unrecognized manifestations of this syndrome, which developed in a 29-year-old man with a history of VP shunt placement following a traumatic brain injury at the age of 9 years. Magnetic resonance imaging showed typical features of chronic intracranial hypotension, and lumbar puncture yielded an unrecordable subarachnoid opening pressure. The calvaria was twice its normal thickness, owing to contraction of the inner table. The paranasal sinuses were expanded, with aeration of the anterior clinoid processes, greater sphenoid wings, and temporal bones. The sella turcica showed a 50\% reduction in cross-sectional area as compared with that in control subjects, resulting in partial extrusion of the pituitary gland. These new features broaden the spectrum of clinical findings associated with low ICP. Secondary installation of a valve to restore normal ICP is recommended to halt progression of these rare complications of VP shunt placement.},
	keywords = {Adult, Brain Injuries, Child, Chronic Disease, Disease Progression, Enophthalmos, Equipment Design, Humans, Intracranial Hypotension, Magnetic Resonance Imaging, Male, Paranasal Sinuses, Pneumocephalus, Sella Turcica, Skull, Tomography, X-Ray Computed, Ventriculoperitoneal Shunt},
	issn = {1933-0715},
	doi = {10.3171/2013.2.PEDS12560},
	author = {Yoon, Michael K and Parsa, Andrew T and Horton, Jonathan C}
}
@article {1460371,
	title = {Giant Cell Arteritis in Black Patients: Do We Know How Rare It Is?},
	journal = {JAMA Ophthalmol},
	year = {2019},
	month = {2019 Aug 08},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2019.2933},
	author = {Yoon, Michael K and Rizzo, Joseph F}
}
@article {341781,
	title = {Orbital cerebrospinal fluid accumulation after complicated pterional-orbitozygomatic craniotomy.},
	journal = {J Neuroophthalmol},
	volume = {34},
	number = {4},
	year = {2014},
	month = {2014 Dec},
	pages = {346-9},
	abstract = {We describe 2 patients who developed postoperative orbital cerebrospinal fluid (CSF) collection after orbitozygomatic pterional craniotomy. An 18-year-old woman underwent exploratory pterional-orbitozygomatic craniotomy. Five days postoperatively, after removal of a lumbar drain, proptosis and a compressive optic neuropathy developed. Computed tomography demonstrated a CSF collection contiguous with the craniotomy site. Resolution followed percutaneous aspiration and replacement of the lumbar drain. A 57-year-old woman underwent a pterional-orbitozygomatic craniotomy for removal of a left anterior clinoid meningioma, complicated by a large left hemorrhagic stroke requiring decompressive hemicraniectomy. Extracranial CSF collections accumulated in both the orbit and subgaleal spaces. Resolution followed placement of an external ventricular drain. Based on these cases, the mechanism seems to be the combination of iatrogenic formation of a communication with the subarachnoid space and elevated intracranial pressure. Resolution was achieved by normalizing intracranial pressure.},
	issn = {1536-5166},
	doi = {10.1097/WNO.0000000000000125},
	author = {Yoon, Michael K and Piluek, Wachirapon Jordan and Ruggiero, Jason P and McDermott, Michael W and McCulley, Timothy J}
}
@article {1363233,
	title = {Canaliculops: clinicopathologic features and treatment with marsupialization},
	journal = {Am J Ophthalmol},
	volume = {156},
	number = {5},
	year = {2013},
	month = {2013 Nov},
	pages = {1062-1068.e1},
	abstract = {PURPOSE: To report the features of the rare and under-recognized condition of canaliculops (or canaliculocele) of the eyelid, which is a dilation of the canaliculus, and to evaluate treatment with marsupialization. DESIGN: Retrospective interventional case series. METHODS: The records of 2 patients with canaliculops from the Massachusetts Eye and Ear Infirmary were reviewed. Data collected included clinical history, surgical technique, histopathologic analysis, and comparative immunohistochemical analysis of a range of cytokeratins in normal conjunctival epithelium, normal canalicular epithelium, and canaliculops epithelium. RESULTS: Two women, 53 and 66 years of age, experienced chronic, noninflammatory, painless medial eyelid and eyelid margin fluctuant swelling after earlier trauma or eyelid surgery. The external mass was accompanied by a whitish opalescent or bluish discoloration of a palpebral surface bulge. Biopsy revealed multilaminar (up to 12 cells thick), nonkeratinizing, tightly packed small squamous epithelial cells that surmounted a highly regimented basal layer with a picket fence arrangement. No goblet cells or subepithelial inflammation were present. Immunohistochemistry revealed only superficial CK7 immunostaining and positive patchy suprabasilar CK17 staining in the canaliculops epithelium, contrasting with their full-thickness positivity and negativity, respectively, in normal conjunctival epithelium. Marsupialization achieved resolution of the condition in each patient. CONCLUSIONS: An improved awareness of the normal canalicular epithelial structure and its immunohistochemical features can definitively separate canaliculops from conjunctival cysts. Previous treatment of canaliculops has involved complete excisions. Canaliculops may, however, be effectively treated with less invasive marsupialization while obtaining an adequate biopsy specimen for histopathologic diagnosis.},
	keywords = {Aged, Biomarkers, Chronic Disease, Cysts, Eyelid Diseases, Female, Humans, Immunohistochemistry, Keratin-17, Keratin-7, Lacrimal Apparatus, Lacrimal Apparatus Diseases, Middle Aged, Ophthalmologic Surgical Procedures, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2013.06.008},
	author = {Yoon, Michael K and Jakobiec, Frederick A and Mendoza, Pia R}
}
@article {1351219,
	title = {Autologous dermal grafts as posterior lamellar spacers in the management of lower eyelid retraction},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {30},
	number = {1},
	year = {2014},
	month = {2014 Jan-Feb},
	pages = {64-8},
	abstract = {PURPOSE: To determine the safety and efficacy of autologous postauricular dermal grafts as posterior lamellar spacing material in patients with lower eyelid retraction. METHODS: At a tertiary care institution, 10 eyelids of 10 patients (7 men, 3 women; mean 56 years, range 24-78) who underwent repair of lower eyelid retraction using a postauricular dermal graft between July 2008 and December 2010 were retrospectively assessed. Data collected included patient demographics, etiology of retraction, and surgical history. Outcome measures included preoperative and postoperative eyelid position and surgery-related complications. RESULTS: Postoperative results were favorable: mean preoperative inferior scleral show was 3.3 {\textpm} 2.6 mm compared with 0.3 {\textpm} 1.2 mm postoperatively, p = 0.004 (paired t test). Mean follow up was 39.2 weeks (range 12-94). Complications included keratinization of the graft with vellus hair growth (n = 1) and ectropion (n = 1), both corrected with minor surgical interventions. One patient achieved overcorrection but declined further treatment. No donor site complications were encountered. CONCLUSIONS: These data suggest postauricular dermal grafts are effective posterior lamellar spacers in the correction of eyelid retraction. They have adequate rigidity whilst maintaining sufficient pliability to mold to the globe. Resorption, common to acellular dermis matrix allografts and xenografts, was not encountered. Donor site complications were not encountered. Complications shared with other material include overcorrection and ectropion. Complications unique to autologous dermis include keratinization and hair growth.},
	keywords = {Adult, Aged, Dermis, Ear, Eyelid Diseases, Female, Humans, Male, Middle Aged, Reconstructive Surgical Procedures, Retrospective Studies, Skin Transplantation, Suture Techniques, Transplantation, Autologous, Treatment Outcome, Young Adult},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000000012},
	author = {Yoon, Michael K and McCulley, Timothy J}
}
@article {1603858,
	title = {Spheno-Orbital Dermoid Masquerading as Recurrent Orbital Abscess},
	journal = {Ophthalmic Plast Reconstr Surg},
	volume = {37},
	number = {6},
	year = {2021},
	month = {2021 Nov-Dec 01},
	pages = {e213-e215},
	abstract = {A 10-month-old girl presented with eyelid edema and erythema that did not improve with systemic antibiotics. Due to a lack of improvement, MRI was performed to avoid ionizing radiation from CT. An orbital abscess was recognized and drained. However, the abscess recurred 2 times. CT scan was performed and a tract in the sphenoid bone helped to diagnose a congenital dural sinus tract with dermoid. Definitive surgery was performed with neurosurgery to remove the entire tract including cutaneous connection. CT scan proved critical to diagnosis and should be considered in infants in select cases despite the concern for ionizing radiation in this vulnerable age group.},
	keywords = {Abscess, Dermoid Cyst, Female, Humans, Infant, Magnetic Resonance Imaging, Neoplasm Recurrence, Local, Orbital Cellulitis},
	issn = {1537-2677},
	doi = {10.1097/IOP.0000000000002026},
	author = {Yoon, Michael K and Habib, Larissa A}
}
@article {1466896,
	title = {Long-term outcomes of systemic corticosteroid-sparing immunomodulatory therapy for Birdshot Retinochoroidopathy},
	journal = {Ocul Immunol Inflamm},
	year = {2019},
	month = {2019 Sep 30},
	pages = {1-9},
	abstract = {: To report the visual prognosis, electroretinography (ERG) and perimetry outcomes of systemic corticosteroid-sparing immunomodulatory treatment (IMT) for birdshot retinochoroidopathy (BSRC). : Retrospective non-comparative case series of 132 patients (264 eyes) with BSRC treated with IMT from Massachusetts Eye Research and Surgery Institution. : The average follow-up time was 60.1 months. After one year on IMT, 39.4\% showed no clinically active inflammation. After 5 years of IMT, 78.0\% had no signs of clinical inflammation. No significant differences were observed on best-corrected visual acuity (BCVA), ERG parameters, and perimetry parameters between baseline and subsequent visits on IMT. : Long-term systemic corticosteroid-sparing IMT was associated with a low rate of BSRC disease exacerbation. While differences were seen on testing parameters, they were not consistent trends and difference were attributed to variability of testing or fluctuation of inflammation that may be expected in the course of the disease.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2019.1641610},
	author = {You, Caiyun and Lasave, Andres F and Kubaisi, Buraa and Syeda, Sarah and Ma, Lina and Wai, Kelvin Cheng Kah and Diaz, Mikhail Hernandez and Walsh, Marisa and Stephenson, Andrew and Montieth, Alyssa and Foster, C Stephen}
}
@article {1109901,
	title = {Rituximab Induction and Maintenance Treatment in Patients with Scleritis and Granulomatosis with Polyangiitis (Wegener{\textquoteright}s)},
	journal = {Ocul Immunol Inflamm},
	year = {2017},
	month = {2017 Jun 19},
	pages = {1-8},
	abstract = {AIMS: To evaluate the efficacy and safety of rituximab (RTX) induction and maintenance treatment for patients with scleritis and granulomatosis with polyangiitis (GPA), Wegener{\textquoteright}s. METHODS: Nine patients (12 eyes) with scleritis with GPA who did not respond to corticosteroids and more than one immunosuppressive agent who received ongoing maintenance RTX treatment were identified. Demographics and outcome measures were recorded. RESULTS: Median follow-up time of 30 months (range, 15 to 87 months). All 12 eyes achieved remission during the RTX maintenance period with a median time in remission of 14 months (range, 5-76 months), and median interval between RTX initiation and inactive disease of 5 months (range, 2-8 months). Two eyes in two patients relapsed. One received steroid eye drops, and the other received a short-term increased dose of intravenous corticosteroids. CONCLUSIONS: RTX was effective as an induction and maintenance treatment in our small cohort of patients with GPA-associated scleritis.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2017.1327602},
	author = {You, Caiyun and Ma, Lina and Lasave, Andres F and Foster, C Stephen}
}
@article {1016146,
	title = {Rituximab in the treatment of ocular cicatricial pemphigoid: a retrospective cohort study},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {255},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {1221-1228},
	abstract = {PURPOSE: The purpose was to evaluate the effectiveness and safety of rituximab (RTX) for the treatment of patients with aggressive ocular cicatricial pemphigoid (OCP). METHODS: A review of patient records at a tertiary referral center with biopsy confirmed OCP who presented between 2006 and 2016. Sixty-one eyes of 32 patients with symptomatic OCP who received treatment with RTX monotherapy or RTX in combination with additional immunomodulatory treatment (IMT) were evaluated. Main outcomes included clinically evident remission of disease, the percentage of corticosteroid sparing patients, stage of OCP (Foster), best corrected visual acuity, and treatment complications. Remission was defined as absence of progressive scarring and active ocular inflammation for >= 2\&nbsp;months. Partial remission/responding was defined as disease control and clinical improvement for >= 2\&nbsp;months. RESULTS: Mean age at the initiation of RTX treatment was 59.1\&nbsp;years (range, 24-80 years) with a median follow-up time after RTX initiation of 32\&nbsp;months (range, 14 to 127\&nbsp;months). Twenty-six patients achieved clinical remission with an average sustained remission of 24.5\&nbsp;months (from 9\&nbsp;months to 84\&nbsp;months). RTX monotherapy was used in six patients, RTX in combination with intravenous immunoglobulin in 14 patients, and RTX with intravenous immunoglobulin and/or with other IMT agent in six patients. Seven eyes (11.5\%) of six patients had favorable response to RTX and achieved response and partial remission, while inflammation remained active in the other seven eyes (11.5\%) of four patients though there was no progressive scarring. At the last visit, three patients (9.4\%) were on topical corticosteroid, three patients (9.4\%) were treated with systemic corticosteroid treatments, and the other 26 patients (81.2\%) achieved corticosteroid sparing therapy. Five eyes (8.2\%) progressed one Foster stage. No other cicatrization progression or worsening of LogMAR visual acuity (p = 0.641) was observed during the follow-up period. Adverse events included leukopenia in three patients (9.4\%), anemia in two patients (6.2\%), liver enzyme elevation in three patients (9.4\%) who were also on another concomitant IMT drug, and Epstein-Barr Virus infection and sinus infection in one patient each (3.1\%). No other severe adverse events were noted during the follow-up period. CONCLUSIONS: These retrospective data suggest that RTX is efficacious and well tolerated when included for the treatment of OCP. Controlled studies are necessary to identify the role of this IMT agent in the therapeutic arsenal, especially its optimum dose and duration of administration.},
	issn = {1435-702X},
	doi = {10.1007/s00417-017-3603-3},
	author = {You, Caiyun and Lamba, Neerav and Lasave, Andres F and Ma, Lina and Diaz, Mikhail Hernandez and Foster, C Stephen}
}
@article {1661824,
	title = {Controversies in Pediatric Angle Surgery and Secondary Surgical Treatment},
	journal = {Semin Ophthalmol},
	year = {2022},
	month = {2022 Dec 06},
	pages = {1-7},
	abstract = {Pediatric glaucoma is a constellation of challenging ophthalmic conditions that, left untreated, can result in irreversible vision loss. The mainstay of treatment for primary congenital glaucoma and select secondary glaucoma subtypes is angle surgery, either trabeculotomy or goniotomy. More recently, MIGS devices have been utilized to enhance the efficacy of these procedures. Despite the high success rates of these primary surgical options, refractory cases are challenging to manage. There is no consensus on the next step of treatment following primary angle surgery. Glaucoma drainage devices and trabeculectomies have been the traditional options, with laser treatment reserved for more severe cases. The benefits and disadvantages of each of these options are discussed.},
	issn = {1744-5205},
	doi = {10.1080/08820538.2022.2152711},
	author = {Young, Alexander K and VanderVeen, Deborah K}
}
@article {1532342,
	title = {Monitoring Glaucomatous Functional Loss Using an Artificial Intelligence-Enabled Dashboard},
	journal = {Ophthalmology},
	volume = {127},
	number = {9},
	year = {2020},
	month = {2020 Sep},
	pages = {1170-1178},
	abstract = {PURPOSE: To develop an artificial intelligence (AI) dashboard for monitoring glaucomatous functional loss. DESIGN: Retrospective, cross-sectional, longitudinal cohort study. PARTICIPANTS: Of 31 591 visual fields (VFs) on 8077 subjects, 13 231 VFs from the most recent visit of each patient were included to develop the AI dashboard. Longitudinal VFs from 287 eyes with glaucoma were used to validate the models. METHOD: We entered VF data from the most recent visit of glaucomatous and nonglaucomatous patients into a "pipeline" that included principal component analysis (PCA), manifold learning, and unsupervised clustering to identify eyes with similar global, hemifield, and local patterns of VF loss. We visualized the results on a map, which we refer to as an "AI-enabled glaucoma dashboard." We used density-based clustering and the VF decomposition method called "archetypal analysis" to annotate the dashboard. Finally, we used 2 separate benchmark datasets-one representing "likely nonprogression" and the other representing "likely progression"-to validate the dashboard and assess its ability to portray functional change over time in glaucoma. MAIN OUTCOME MEASURES: The severity and extent of functional loss and characteristic patterns of VF loss in patients with glaucoma. RESULTS: After building the dashboard, we identified 32 nonoverlapping clusters. Each cluster on the dashboard corresponded to a particular global functional severity, an extent of VF loss into different hemifields, and characteristic local patterns of VF loss. By using 2 independent benchmark datasets and a definition of stability as trajectories not passing through over 2 clusters in a left or downward direction, the specificity for detecting "likely nonprogression" was 94\% and the sensitivity for detecting "likely progression" was 77\%. CONCLUSIONS: The AI-enabled glaucoma dashboard, developed using a large VF dataset containing a broad spectrum of visual deficit types, has the potential to provide clinicians with a user-friendly tool for determination of the severity of glaucomatous vision deficit, the spatial extent of the damage, and a means for monitoring the disease progression.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2020.03.008},
	author = {Yousefi, Siamak and Tobias Elze and Pasquale, Louis R and Saeedi, Osamah and Wang, Mengyu and Shen, Lucy Q and Wellik, Sarah R and De Moraes, Carlos G and Myers, Jonathan S and Boland, Michael V}
}
@article {1647905,
	title = {Machine-identified Patterns of Visual Field Loss and An Association with Rapid Progression in the Ocular Hypertension Treatment Study},
	journal = {Ophthalmology},
	year = {2022},
	month = {2022 Jul 08},
	abstract = {PURPOSE: To identify patterns of visual field (VF) loss based on unsupervised machine learning and to identify patterns that are associated with rapid progression. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: A total of 2231 abnormal VFs from 205 eyes of 176 OHTS participants followed over approximately 16 years. METHODS: VFs were assessed by an unsupervised deep archetypal analysis algorithm as well as an OHTS certified VF reader to identify prevalent patterns of VF loss. Machine-identified patterns of glaucoma damage were compared against those patterns previously identified (expert-identified) in the OHTS in 2003. Based on the longitudinal VFs of each eye, VF loss patterns that were strongly associated with rapid glaucoma progression were identified. MAIN OUTCOME MEASURES: Machine-expert correspondence and type of patterns of VF loss associated with rapid progression. RESULTS: The average VF mean deviation (MD) at conversion to glaucoma was -2.7 dB (Standard Deviation (SD) = 2.4 dB) while the average MD of the eyes at the last visit was -5.2 dB (SD = 5.5 dB). Fifty out of 205 eyes had MD rate of -1 dB/year or worse and were considered rapid progressors. Eighteen machine-identified patterns of VF loss were compared with expert-identified patterns in which 13 patterns of VF loss were similar. The most prevalent expert-identified patterns included partial arcuate, paracentral, and nasal step defects, and the most prevalent machine-identified patterns included temporal wedge, partial arcuate, nasal step, and paracentral VF defects. One of the machine-identified patterns of VF loss predicted future rapid VF progression after adjustment for age, sex, and initial MD. CONCLUSIONS: An automated machine learning system can identify patterns of VF loss and could provide objective, and reproducible nomenclature for characterizing early signs of visual defects and rapid progression in patients with glaucoma.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.07.001},
	author = {Yousefi, Siamak and Pasquale, Louis R and Boland, Michael V and Johnson, Chris A}
}
@article {1363236,
	title = {Caveolin-1 associated adenovirus entry into human corneal cells},
	journal = {PLoS One},
	volume = {8},
	number = {10},
	year = {2013},
	month = {2013},
	pages = {e77462},
	abstract = {The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD) profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling.},
	keywords = {Adenoviruses, Human, Animals, Caveolin 1, Cell Line, Cholesterol, Cornea, Female, Fibroblasts, Humans, Mice, Mice, Knockout, src-Family Kinases, Viral Tropism, Virus Internalization},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0077462},
	author = {Yousuf, Mohammad A and Zhou, Xiaohong and Mukherjee, Santanu and Chintakuntlawar, Ashish V and Lee, Jeong Yoon and Ramke, Mirja and Chodosh, James and Rajaiya, Jaya}
}
@article {1626091,
	title = {Altered Resting State Functional Activity of Brain Regions in Neovascular Glaucoma: A Resting-State Functional Magnetic Resonance Imaging Study},
	journal = {Front Neurosci},
	volume = {15},
	year = {2021},
	month = {2021},
	pages = {800466},
	abstract = {Background: Neovascular glaucoma (NVG) is a serious eye disease that causes irreversible damage to the eye. It can significantly increase intraocular pressure and cause severe pain, as well as abnormal activity in the cortical and pre-cortical visual systems. However, there are few studies in this area. This trial assessed the altered regional brain activity in patients with NVG using the percentage of fluctuation amplitude (PerAF) method. Methods: Resting-state functional MRI (rs-fMRI) scans were conducted in 18 individuals with NVG and 18 healthy controls (HCs), matched for education level, gender, and age. The PerAF method was applied to assess brain activity. Mean PerAF values of brain regions in NVG and HCs were compared using receiver operating characteristic (ROC) curves. Results: Lower PerAF values were found in the NVG group than in controls in the right anterior cingulate and paracingulate gyri (ACG.R), right superior occipital gyrus (SOG.R) and left superior frontal gyrus (orbital part) (ORBsup.L) (p \&lt; 0.001). In contrast, PerAF value was higher in NVG patients than in controls in the left inferior temporal gyrus (ITG.L) (p \&lt; 0.001). The hospital anxiety and depression scale (HADS) and visual analog score (VAS) were significantly and positively correlated with PerAF in ITG.L (r = 0.9331, p \&lt; 0.0001; and r = 0.7816, p = 0.0001, respectively). Conclusion: Abnormal activity in the patient{\textquoteright}s brain regions further confirms that the NVG affects the entire brain, not just the visual pathways and posterior retinal mechanisms (including the hypothalamic lateral geniculate nucleus and the primary visual cortex). This strengthens our understanding of the NVG and provides potential diagnostic and therapeutic support for patients who are difficult to diagnose and treat early.},
	issn = {1662-4548},
	doi = {10.3389/fnins.2021.800466},
	author = {Yu, Chao and Li, Chu-Qi and Ge, Qian-Min and Shu, Hui-Ye and Liao, Xu-Lin and Pan, Yi-Cong and Wu, Jie-Li and Su, Ting and Zhang, Li-Juan and Liang, Rong-Bin and Shao, Yi and Zeng, Er-Ming}
}
@article {1608589,
	title = {Author Correction: Altered spontaneous activity in the frontal gyrus in dry eye: a resting-state functional MRI study},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Aug 30},
	pages = {17653},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-97182-x},
	author = {Yu, Kang and Guo, Yu and Ge, Qian-Min and Su, Ting and Shi, Wen-Qing and Zhang, Li-Juan and Shu, Hui-Ye and Pan, Yi-Cong and Liang, Rong-Bin and Li, Qiu-Yu and Shao, Yi}
}
@article {1483617,
	title = {Neurokinin-1 Receptor Antagonism Ameliorates Dry Eye Disease by Inhibiting Antigen-Presenting Cell Maturation and T Helper 17 Cell Activation},
	journal = {Am J Pathol},
	volume = {190},
	number = {1},
	year = {2020},
	month = {2020 Jan},
	pages = {125-133},
	abstract = {Neuroinflammation plays an important role in the pathogenesis of ocular surface disease, including dry eye disease (DED), but little is known about the contribution of substance P (SP) to DED. In this study, we investigated the expression of SP at the ocular surface and evaluated its effect on maturation of antigen-presenting cells (APCs), the key cell component involved in the induction of type 17 helper T-cell (Th17) response in DED. The effect of topical blockade of SP signaling was further investigated using neurokinin-1 receptor (NK1R) inhibitors on APC maturation, Th17 cell activation, and disease severity in a mouse model of DED. The results demonstrate that SP is constitutively expressed at the ocular surface, and trigeminal ganglion neurons are the major source of SP in DED. SP derived from trigeminal ganglion enhanced the expression of major histocompatibility complex class II maturation marker by bone marrow-derived dendritic cells, an effect that is abrogated by blockade of SP signaling using NK1R antagonist spantide. Finally, using a well-established murine model of DED, topical treatment of DED mice with NK1R antagonists CP-99,994 and L-733,060 suppressed APC acquisition of major histocompatibility complex class II, reduced Th17 cell activity, and ameliorated DED severity. These findings are of translational value, as they suggest that antagonizing NK1R-mediated SP signaling may be an effective strategy in suppressing Th17-mediated ocular surface disease.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2019.09.020},
	author = {Yu, Man and Lee, Sang-Mok and Lee, Hyun Soo and Amouzegar, Afsaneh and Nakao, Takeshi and Chen, Yihe and Dana, Reza}
}
@article {1351220,
	title = {The potential of stem cell-based therapy for retinal repair},
	journal = {Neural Regen Res},
	volume = {9},
	number = {11},
	year = {2014},
	month = {2014 Jun 01},
	pages = {1100-3},
	issn = {1673-5374},
	doi = {10.4103/1673-5374.135311},
	author = {Yu, Honghua and Cheng, Lin and Cho, Kin-Sang}
}
@article {959491,
	title = {Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016 Nov 16},
	pages = {37216},
	abstract = {Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6\%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100\% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD.},
	issn = {2045-2322},
	doi = {10.1038/srep37216},
	author = {Yu, Zhiwu and Zeng, Zhiwei and Zhang, Jing and Pan, Yuxian and Chen, Manjun and Guo, Yonghui and Yu, Nan and Chodosh, James and Fu, Ning and Che, Xiaoyan and Zhang, Qiwei}
}
@article {1532360,
	title = {COMBINED PNEUMATIC AND ENZYMATIC VITREOLYSIS FOR SEVERE CASES OF VITREOMACULAR TRACTION},
	journal = {Retin Cases Brief Rep},
	volume = {16},
	number = {5},
	year = {2022},
	month = {2022 Sep 01},
	pages = {631-636},
	abstract = {PURPOSE: To evaluate the efficacy of combined pneumatic and enzymatic vitreolysis for treatment of severe cases of vitreomacular traction (VMT). METHODS: We analyzed a retrospective, consecutive series of five patients diagnosed with severe VMT refractory to pneumatic vitreolysis who then received an additional ocriplasmin injection while their gas bubble from pneumatic vitreolysis was still present between February 2015 and February 2019. Vitreomacular traction release was confirmed using spectral-domain optical coherence tomography. RESULTS: Four of the five patients treated with combined pneumatic and enzymatic vitreolysis achieved VMT release by Day 28, and all cases eventually achieved complete VMT release. In addition to having VMT refractory to pneumatic vitreolysis, patient characteristics included broad adhesion diameter (\&gt;1,500 {\textmu} m, n = 1), presence of epiretinal membrane (n = 2), age \&gt;65 years (n = 4), and pseudophakia (n = 1). The visual acuity improved by three or more lines at 6 months in both of the patients with initial vision worse than 20/50 on an Early Treatment Diabetic Retinopathy Study chart but not in those whose vision was already fairly good (i.e., visual acuity \&gt;20/60). None of the patients experienced the following complications after receiving this combined treatment: retinal tears or detachments, vitreous floaters, and ellipsoid zone changes. CONCLUSION: Sequential, combined pneumatic and enzymatic vitreolysis resulted in VMT release in all 5 cases (4 cases by 28 days) and may be a potentially useful alternative to surgical intervention for refractory VMT cases.},
	keywords = {Aged, Fibrinolysin, Humans, Intravitreal Injections, Peptide Fragments, Retinal Perforations, Retrospective Studies, Tomography, Optical Coherence, Traction, Vision Disorders, Vitreous Detachment},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000001047},
	author = {Yu, Gina and Seto, Brendan K and Yamada, Keiko and Zeng, Ke and Arroyo, Jorge G}
}
@article {1688266,
	title = {Ocular microvascular alteration in Sj{\"o}gren{\textquoteright}s syndrome treated with hydroxychloroquine: an OCTA clinical study},
	journal = {Ther Adv Chronic Dis},
	volume = {14},
	year = {2023},
	month = {2023},
	pages = {20406223231164498},
	abstract = {BACKGROUND: Sj{\"o}gren{\textquoteright}s syndrome (SjS) is a rare autoimmune disease, and despite our knowledge of SjS, we still lack effective treatments. Chloroquine drugs used to treat autoimmune diseases are still the primary medicine for SjS but increase the risk of chloroquine retinopathy. OBJECTIVES: The objective of this study is to use Optical Coherence Tomography Angiography (OCTA) images to monitor the microvascular changes in the fundus of SjS patients after hydroxychloroquine (HCQ) treatment and the feasibility of using them as diagnostic indicators. DESIGN: This is a retrospective observational cohort study. METHODS: Twelve healthy controls (HCs group; 24 eyes), 12 SjS patients (SjS group; 24 eyes), and 12 SjS patients treated with HCQ (HCQ group; 24 eyes) were recruited. Three-dimensional OCTA images of the retina were collected, and microvascular density was calculated for each eye. OCTA image segmentation for analysis was conducted using the central wheel division method (C1-C6), hemisphere segmentation method (SR, SL, IL, and IR), and the early treatment of diabetic retinopathy study method (ETDRS) (R, S, L, and I). RESULTS: Retinal microvascular density was significantly lower in the SjS patients compared to the HCs group (p \&lt; 0.05) and much lower in the HCQ group compared to the SjS patients (p \&lt; 0.05). The SjS and HCQ groups differed in the I, R, SR, IL, and IR regions in the superficial and deep retina and the S region in the superficial retina. The ROC curves of the relationship between the HCs and SjS groups and between the SjS and HCQ groups demonstrated good classification accuracy. CONCLUSION: HCQ may contribute significantly to the microvascular alteration in SjS. Microvascular alteration is a potential marker with adjunctive diagnostic value. The MIR and the OCTA images of I, IR, and C1 regions showed high accuracy in minoring the alteration.},
	issn = {2040-6223},
	doi = {10.1177/20406223231164498},
	author = {Yu, Chao and Zou, Jie and Ge, Qian-Min and Liao, Xu-Lin and Pan, Yi-Cong and Wu, Jie-Li and Su, Ting and Zhang, Li-Juan and Liang, Rong-Bin and Shao, Yi}
}
@article {1598029,
	title = {Altered spontaneous activity in the frontal gyrus in dry eye: a resting-state functional MRI study},
	journal = {Sci Rep},
	volume = {11},
	number = {1},
	year = {2021},
	month = {2021 Jun 21},
	pages = {12943},
	abstract = {This study investigated neurologic changes in patients with dry eye (DE) by functional magnetic resonance imaging (fMRI) and to used regional homogeneity (ReHo) analysis to clarify the relationship between these changes and clinical features of DE. A total of 28 patients with DE and 28 matched healthy control (HC) subjects (10 males and 18 females in each group) were enrolled. fMRI scans were performed in both groups. We carried out ReHo analysis to assess differences in neural activity between the 2 groups, and receiver operating characteristic curve (ROC) analysis was performed to evaluate the performance of ReHo values of specific brain areas in distinguishing DE patients from HCs. The relationship between average ReHo values and clinical characteristics was assessed by correlation analysis. ReHo values of the middle frontal gyrus, inferior frontal gyrus, and superior frontal gyrus were significantly lower in DE patients compared to HCs. The ROC analysis showed that ReHo value had high accuracy in distinguishing between DE patients and HCs (P \&lt; 0.0001). The ReHo values of the middle frontal gyrus and dorsolateral superior frontal gyrus were correlated to disease duration (P \&lt; 0.05). Symptoms of ocular surface injury in DE patients are associated with dysfunction in specific brain regions, which may underlie the cognitive impairment, psychiatric symptoms, and depressive mood observed in DE patients. The decreased ReHo values of some brain gyri in this study may provide a reference for clinical diagnosis and determination of treatment efficacy.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-92199-8},
	author = {Yu, Kang and Guo, Yu and Ge, Qian-Ming and Su, Ting and Shi, Wen-Qing and Zhang, Li-Juan and Shu, Hui-Ye and Pan, Yi-Cong and Liang, Rong-Bin and Li, Qiu-Yu and Shao, Yi}
}
@article {1661847,
	title = {UVA induces retinal photoreceptor cell death via receptor interacting protein 3 kinase mediated necroptosis},
	journal = {Cell Death Discov},
	volume = {8},
	number = {1},
	year = {2022},
	month = {2022 Dec 12},
	pages = {489},
	abstract = {Ultraviolet light A (UVA) is the only UV light that reaches the retina and can cause indirect damage to DNA via absorption of photons by non-DNA chromophores. Previous studies demonstrate that UVA generates reactive oxygen species (ROS) and leads to programmed cell death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor interacting protein 1 and 3 (RIPK1 and RIPK3) kinases, key signaling molecules of PCD, in UVA-induced photoreceptor injury using in vitro and ex vivo models. UVA irradiation activated RIPK3 but not RIPK1 and mediated necroptosis through MLKL that lie downstream of RIPK3 and induced apoptosis through increased oxidative stress. Moreover, RIPK3 but not RIPK1 inhibition suppresses UVA-induced cell death along with the downregulation of MLKL and attenuates the levels of oxidative stress and DNA fragmentation. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced necroptosis cell death in photoreceptors and highlight RIPK3 potential as a neuroprotective target.},
	issn = {2058-7716},
	doi = {10.1038/s41420-022-01273-1},
	author = {Yu, Zhen and Correa, Victor S M C and Efstathiou, Nikolaos E and Albertos-Arranz, Henar and Chen, XiaoHong and Ishihara, Kenji and Iesato, Yasuhiro and Narimatsu, Toshio and Ntentakis, Dimitrios and Vavvas, Demetrios G}
}
@article {630196,
	title = {EFFICACY AND SAFETY OF TREATMENT OPTIONS FOR VITREOMACULAR TRACTION: A Case Series and Meta-Analysis.},
	journal = {Retina},
	volume = {36},
	number = {7},
	year = {2016},
	month = {2016 Jul},
	pages = {1260-70},
	abstract = {PURPOSE: To evaluate treatment options for vitreomacular traction (VMT). METHODS: A retrospective, consecutive case series and a literature search with Boolean search logic. A random-effects meta-analysis was conducted to combine the rates of VMT resolution per treatment. Patients from studies analyzed were placed into cohorts based on the treatment received. RESULTS: CASE SERIES: Zero of 10 control, 3 of 7 intravitreal ocriplasmin (IVO, P = 0.10), 7 of 8 intravitreal expansile gas (pneumatic vitreolysis, PV, P \&lt; 0.01), and 10 of 10 pars plana vitrectomy (P \&lt; 0.01)-treated eyes experienced VMT release (VMTr) at Day 28. No patients developed retinal tears or detachment. One PV-treated (12.5\%) eye developed a macular hole. Meta-analysis: Twenty-three of 131 prospective or retrospective and consecutive articles were included. Sixty-three eyes were treated with PV, 726 eyes were treated with intravitreal ocriplasmin, and 253 eyes were characterized as the control group (saline injection). The weighted rate of VMT resolution for the control group was 0.09 (95\% confidence interval [CI]: 0.06-0.13), PV was 0.84 (95\% CI: 0.76-0.92), and intravitreal ocriplasmin was 0.26 (95\% CI: 0.23-0.29). CONCLUSION: Our analysis found that PV releases VMT in most patients and suggest that PV may be as effective or superior to nonsurgical options for VMTr at Day 28 with a similar risk profile.},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000000909},
	author = {Yu, Gina and Duguay, James and Marra, Kyle V and Gautam, Shiva and Le Guern, Guillaume and Begum, Shimul and Sharifzadeh, Arya and Arroyo, Jorge G}
}
@article {1347450,
	title = {BILATERAL CENTRAL RETINAL VEIN OCCLUSIONS IN A YOUNG PATIENT WITH A HISTORY OF EOSINOPHILIC PNEUMONIA AND THALAMIC STROKE},
	journal = {Retin Cases Brief Rep},
	volume = {12},
	number = {4},
	year = {2018},
	month = {2018 Fall},
	pages = {300-304},
	abstract = {PURPOSE: To describe a case of a central retinal vein occlusion in a young patient with a history of eosinophilic pneumonia. METHODS: A retrospective case report of a 45-year-old woman with acute painless vision loss for 9 days after multiple episodes of eosinophilic pneumonia and thalamic stroke. Fluorescein angiography, spectral domain optical coherence tomography, and clinical examination were performed. She was then treated with intravitreal bevacizumab and pan-retinal photocoagulations. RESULTS: Retinal examination revealed tortuosity and dilatation of all branches of the central retinal vein and flame-shaped hemorrhages in all four quadrants of the right eye associated with cystoid macular edema, optic disc edema, and cotton wool spots. The left eye had mild venous dilatation and tortuosity with a few dot retinal hemorrhages in the far temporal periphery. The cystoid macular edema resolved after one intravitreal injection of bevacizumab and remained resolved at the most recent follow-up. Fluorescein angiography at the most recent follow-up revealed vasculitis in the far periphery of the nontreated eye. CONCLUSION: Central retinal vein occlusion in young patients is a rare condition often presenting as a manifestation of an underlying inflammatory or hematological disorder. Combined anti-vascular endothelial growth factor treatment and pan-retinal photocoagulation may have resolved the associated cystoid macular edema in this case, although continued observation is necessary.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Female, Humans, Light Coagulation, Middle Aged, Pulmonary Eosinophilia, Retinal Vein Occlusion, Retrospective Studies, Stroke, Thalamic Diseases},
	issn = {1937-1578},
	doi = {10.1097/ICB.0000000000000501},
	author = {Yu, Gina and Sun, Peng and van Zyl, Tav{\'e} and Tandias, Rachel and Arroyo, Jorge G}
}
@article {439696,
	title = {Computer-aided analyses of mouse retinal OCT images - an actual application report.},
	journal = {Ophthalmic Physiol Opt},
	volume = {35},
	number = {4},
	year = {2015},
	month = {2015 Jul},
	pages = {442-9},
	abstract = {PURPOSE: There is a need for automated retinal optical coherence tomography (OCT) image analysis tools for quantitative measurements in small animals. Some image processing techniques for retinal layer analysis have been developed, but reports about how useful those techniques are in actual animal studies are rare. This paper presents the use of a retinal layer detection method we developed in an actual mouse study that involves wild type and mutated mice carrying photoreceptor degeneration. METHODS: Spectral domain OCT scanning was performed by four experimenters over 12\&nbsp;months on 45 mouse eyes that were wild-type, deficient for ephrin-A2 and ephrin-A3, deficient for rhodopsin, or deficient for rhodopsin, ephrin-A2 and ephrin-A3. The thickness of photoreceptor complex between the outer plexiform layer and retinal pigment epithelium was measured on two sides of the optic disc as the biomarker of retinal degeneration. All the layer detection results were visually confirmed. RESULTS: Overall, 96\% (8519 out of 9000) of the half-side images were successfully processed using our technique in a semi-automatic manner. There was no significant difference in success rate between mouse lines (p\&nbsp;=\&nbsp;0.91). Based on a human observer{\textquoteright}s rating of image quality for images successfully and unsuccessfully processed, the odds ratios for {\textquoteright}easily visible{\textquoteright} images and {\textquoteright}not clear{\textquoteright} images to be successfully processed is 62 and 4, respectively, against {\textquoteright}indistinguishable{\textquoteright} images. Thickness of photoreceptor complex was significantly different across the quadrants compared (p\&nbsp;\&lt;\&nbsp;0.001). It was also found that the average thickness based on 4-point sparse sampling was not significantly different from the full analysis, while the range of differences between the two methods could be up to about 6\&nbsp;μm or 16\% for individual eyes. Differences between mouse lines and progressive thickness reduction were revealed by both sampling measures. CONCLUSIONS: Although the thickness of the photoreceptor complex layer is not even, manual sparse sampling may be as sufficiently accurate as full analysis in some studies such as ours, where the error of sparse sampling was much smaller than the effect size of rhodopsin deficiency. It is also suggested that the image processing method can be useful in actual animal studies. Even for images poorly visible to human eyes the image processing method still has a good chance to extract the complex layer.},
	issn = {1475-1313},
	doi = {10.1111/opo.12213},
	author = {Yu, Dekuang and Zheng, Jin and Zhu, Ruilin and Wu, Nan and Guan, Alex and Cho, Kin-Sang and Chen, Dong Feng and Luo, Gang}
}
@article {1351221,
	title = {Mobilizing endogenous stem cells for retinal repair},
	journal = {Transl Res},
	volume = {163},
	number = {4},
	year = {2014},
	month = {2014 Apr},
	pages = {387-98},
	abstract = {Irreversible vision loss is most often caused by the loss of function and subsequent death of retinal neurons, such as photoreceptor cells-the cells that initiate vision by capturing and transducing signals of light. One reason why retinal degenerative diseases are devastating is that, once retinal neurons are lost, they don{\textquoteright}t grow back. Stem cell-based cell replacement strategy for retinal degenerative diseases are leading the way in clinical trials of transplantation therapy, and the exciting findings in both human and animal models point to the possibility of restoring vision through a cell replacement regenerative approach. A less invasive method of retinal regeneration by mobilizing endogenous stem cells is, thus, highly desirable and promising for restoring vision. Although many obstacles remain to be overcome, the field of endogenous retinal repair is progressing at a rapid pace, with encouraging results in recent years.},
	keywords = {Animals, Cell- and Tissue-Based Therapy, Humans, Regenerative Medicine, Retinal Diseases, Stem Cells},
	issn = {1878-1810},
	doi = {10.1016/j.trsl.2013.11.011},
	author = {Yu, Honghua and Vu, Thi Hong Khanh and Cho, Kin-Sang and Guo, Chenying and Chen, Dong Feng}
}
@article {1511476,
	title = {Self-assembling hydrogel loaded with 5-FU PLGA microspheres as a novel vitreous substitute for proliferative vitreoretinopathy},
	journal = {J Biomed Mater Res A},
	volume = {108},
	number = {12},
	year = {2020},
	month = {2020 Dec},
	pages = {2435-2446},
	abstract = {The vitreous substitute for proliferative vitreoretinopathy (PVR) surgery remains an unmet clinical need in ophthalmology. In our study, we developed an in situ formed hydrogel by crosslinking polyvinyl alcohol (PVA) and chitosan as a potential vitreous substitute. 5-fluorouracil (5-FU) Poly (lactic-co-glycolic acid) (PLGA) microspheres were developed and loaded onto the PVA/chitosan hydrogels to treat PVR. In vitro, PVA/chitosan hydrogels at four concentrations were subjected to morphological, physical, rheological analyses, and cytotoxicity was evaluated together with the characterization of 5-FU PLGA microspheres. In vivo, pharmacologically induce PVR rabbits were performed a vitrectomy. In the PVA group, 3\% PVA/chitosan hydrogel was injected into the vitreous cavity. In the PVA/MS group, 3\% PVA/chitosan hydrogel and 5-FU PLGA microspheres were injected. In the Control group, phosphate-buffered saline was injected. Therapeutic efficacy was evaluated with postoperative examinations and histological analyses. This study demonstrated that the 3\% PVA/chitosan hydrogel showed properties similar to those of the human vitreous and could be a novel in situ crosslinked vitreous substitute for PVR. Loading 5-FU PLGA microspheres onto this hydrogel may represent an effective strategy to improve the prognosis of PVR.},
	issn = {1552-4965},
	doi = {10.1002/jbm.a.36995},
	author = {Yu, Zhen and Ma, Shisi and Wu, Mengfan and Cui, Huan and Wu, Rong and Chen, Sizhe and Xu, Chenlin and Lu, Xiaohe and Feng, Songfu}
}
@article {1623371,
	title = {Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death},
	journal = {Cell Death Discov},
	volume = {7},
	number = {1},
	year = {2021},
	month = {2021 Nov 23},
	pages = {366},
	abstract = {Ultraviolet (UV) is one of the most energetic radiations in the solar spectrum that can result in various tissue injury disorders. Previous studies demonstrated that UVA, which represents 95\% of incident photovoltaic radiation, induces corneal endothelial cells (CECs) death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor-interacting protein 3 kinase (RIPK3), a key signaling molecule of PCD, in UVA-induced injury using a short-term corneal endothelium (CE) culture model. UVA irradiation activated RIPK3 and mediated necroptosis both in mouse CE and primary human CECs (pHCECs). UVA irradiation was associated with upregulation of key necroptotic molecules (DAI, TRIF, and MLKL) that lie downstream of RIPK3. Moreover, RIPK3 inhibition or silencing in primary corneal endothelial cells suppresses UVA-induced cell death, along with downregulation of MLKL in pHCECs. In addition, genetic inhibition or knockout of RIPK3 in mice (RIPK3K51A and RIPK3-/- mice) similarly attenuates cell death and the levels of necroptosis in ex vivo UVA irradiation experiments. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced cell death in CE and indicate its potential as a future protective target.},
	issn = {2058-7716},
	doi = {10.1038/s41420-021-00757-w},
	author = {Yu, Zhen and Efstathiou, Nikolaos E and Correa, Victor S M C and Chen, XiaoHong and Ishihara, Kenji and Iesato, Yasuhiro and Narimatsu, Toshio and Ntentakis, Dimitrios and Chen, Yanyun and Vavvas, Demetrios G}
}
@article {1677726,
	title = {Genome-Wide Associations and Confirmatory Meta-Analyses in Diabetic Retinopathy},
	journal = {Genes (Basel)},
	volume = {14},
	number = {3},
	year = {2023},
	month = {2023 Mar 05},
	abstract = {The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list of significant GWAS discoveries. The top signals were then subjected to meta-analysis using established protocols. The results indicate the need for improved consensus among DR GWASs, highlighting the importance of validation efforts. A subsequent meta-analysis confirmed the association of two SNPs, rs4462262 (ZWINT-MRPS35P3) (odds ratio = 1.38, p = 0.001) and rs7903146 (TCF7L2) (odd ratio = 1.30, p \&lt; 0.001), with DR in independent populations, strengthening the evidence of their true association. We also compiled a list of candidate SNPs for further validation. This study highlights the importance of consistent validation and replication efforts in the field of DR genetics. The two identified gene loci warrant further functional investigation to understand their role in DR pathogenesis.},
	keywords = {Diabetes Mellitus, Diabetic Retinopathy, Genome-Wide Association Study, Humans, Macular Edema, Odds Ratio, Polymorphism, Single Nucleotide},
	issn = {2073-4425},
	doi = {10.3390/genes14030653},
	author = {Yu, Xin Ting and Rong, Shi Song}
}
@article {1347451,
	title = {Associations of breast milk adiponectin, leptin, insulin and ghrelin with maternal characteristics and early infant growth: a longitudinal study},
	journal = {Br J Nutr},
	volume = {120},
	number = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {1380-1387},
	abstract = {Breast milk (BM) hormones have been hypothesised as a nutritional link between maternal and infant metabolic health. This study aimed to evaluate hormone concentrations in BM of women with and without gestational diabetes mellitus (GDM), and the relationship between maternal factors, BM hormones and infant growth. We studied ninety-six nulliparous women with (n 48) and without GDM and their exclusively breastfed term singletons. Women with GDM received dietary therapy or insulin injection for euglycaemia during pregnancy. Hormone concentrations in BM, maternal BMI and infant growth were longitudinally evaluated on postnatal days 3, 42 and 90. Mothers with GDM had decreased concentrations of adiponectin (P colostrum\&lt;0{\textperiodcentered}001; P mature-milk=0{\textperiodcentered}009) and ghrelin (P colostrum=0{\textperiodcentered}011; P mature-milk\&lt;0{\textperiodcentered}001) and increased concentration of insulin in BM (P colostrum=0{\textperiodcentered}047; P mature-milk=0{\textperiodcentered}021). Maternal BMI was positively associated with adiponectin (β=0{\textperiodcentered}06; 95 \% CI 0{\textperiodcentered}02, 0{\textperiodcentered}1; P=0{\textperiodcentered}001), leptin (β=0{\textperiodcentered}16; 95 \% CI 0{\textperiodcentered}12, 0{\textperiodcentered}2; P\&lt;0{\textperiodcentered}001) and insulin concentrations (β=0{\textperiodcentered}06; 95 \% CI 0{\textperiodcentered}02, 0{\textperiodcentered}1; P\&lt;0{\textperiodcentered}001), and inversely associated with ghrelin concentration in BM (β=-0{\textperiodcentered}08; 95 \% CI -0{\textperiodcentered}1, -0{\textperiodcentered}06; P\&lt;0{\textperiodcentered}001). Among the four hormones, adiponectin was inversely associated with infant growth in both the GDM (β weight-for-height=-2{\textperiodcentered}49; 95 \% CI -3{\textperiodcentered}83, -1{\textperiodcentered}15; P\&lt;0{\textperiodcentered}001; β head-circumference=-0{\textperiodcentered}39; 95 \% CI -0{\textperiodcentered}65, -0{\textperiodcentered}13; P=0{\textperiodcentered}003) and healthy groups (β weight-for-height=-1{\textperiodcentered}42; 95 \% CI -2{\textperiodcentered}38, -0{\textperiodcentered}46; P=0{\textperiodcentered}003; β head-circumference=-0{\textperiodcentered}15; 95 \% CI -0{\textperiodcentered}27, -0{\textperiodcentered}03; P=0{\textperiodcentered}007). Maternal BMI and GDM are important determinants of BM hormone concentrations. Milk-borne adiponectin is determined by maternal metabolic status and plays an independent down-regulating role in early infant growth.},
	issn = {1475-2662},
	doi = {10.1017/S0007114518002933},
	author = {Yu, Xin Ting and Rong, Shi Song and Sun, Xiujing and Ding, Guofang and Wan, Weilin and Zou, Liying and Wu, Shaowen and Li, Ming and Wang, Danhua}
}
@article {1589769,
	title = {Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study},
	journal = {Eye (Lond)},
	volume = {36},
	number = {4},
	year = {2022},
	month = {2022 Apr},
	pages = {818-826},
	abstract = {BACKGROUND/OBJECTIVES: REALITY is an international observational retrospective registry of LHON patients evaluating the visual course and outcome in Leber hereditary optic neuropathy (LHON). SUBJECTS/METHODS: Demographics and visual function data were collected from medical charts of LHON patients with visual loss. The study was conducted in 11 study centres in the United States\&nbsp;of America and Europe. The collection period extended from the presymptomatic stage to at least more than one year after onset of vision loss (chronic stage). A Locally Weighted Scatterplot Smoothing (LOWESS) local regression model was used to analyse the evolution of best-corrected visual acuity (BCVA) over time. RESULTS: 44 LHON patients were included; 27 (61\%) carried the m.11778G\&gt;A ND4 mutation, 8 (18\%) carried the m.3460G\&gt;A ND1 mutation, and 9 (20\%) carried the m.14484T\&gt;C ND6 mutation. Fourteen (32\%) patients were under 18 years old at onset of vision loss and 5 (11\%) were below the age of 12. The average duration of follow-up was 32.5 months after onset of symptoms. At the last observed measure, mean BCVA was 1.46 LogMAR in ND4 patients, 1.52 LogMAR in ND1 patients, and 0.97 LogMAR in ND6 patients. The worst visual outcomes were reported in ND4 patients aged at least 15\&nbsp;years old at onset, with a mean BCVA of 1.55 LogMAR and no tendency for spontaneous recovery. The LOESS modelling curve depicted a severe and permanent deterioration of BCVA. CONCLUSIONS: Amongst LHON patients with the three primary mtDNA mutations, adult patients with the m.11778G\&gt;A ND4 mutation had the worst visual outcomes, consistent with prior reports.},
	keywords = {Adolescent, Adult, DNA, Mitochondrial, Europe, Humans, Mutation, Optic Atrophy, Hereditary, Leber, Retrospective Studies},
	issn = {1476-5454},
	doi = {10.1038/s41433-021-01535-9},
	author = {Yu-Wai-Man, Patrick and Newman, Nancy J and Carelli, Valerio and La Morgia, Chiara and Biousse, Val{\'e}rie and Bandello, Francesco M and Clermont, Catherine Vignal and Campillo, Lorena Castillo and Leruez, Stephanie and Moster, Mark L and Cestari, Dean M and Foroozan, Rod and Sadun, Alfredo and Karanjia, Rustum and Jurkute, Neringa and Blouin, Laure and Taiel, Magali and Sahel, Jos{\'e}-Alain and LHON REALITY Study Group}
}
@article {1593841,
	title = {Biomechanical testing of flanged polypropylene sutures in scleral fixation},
	journal = {Am J Ophthalmol},
	year = {2021},
	month = {2021 May 01},
	abstract = {OBJECTIVE: To optimize the flanged belt-loop technique of scleral fixation through biomechanical testing and report clinical outcomes of resultant modifications. DESIGN: Experimental study. METHODS: The force to disinsert flanged polypropylene suture from human cadaveric sclera was assessed using a tensile testing machine and compared to the breaking strengths of 9-0 and 10-0 polypropylene. The effects of modifying suture gauge (5-0, 6-0, 7-0 or 8-0), amount of suture cauterized (0.5 or 1.0mm), and sclerotomy size (27-, 30-, 32-, 33-gauge) were investigated. Belt-loop intrascleral fixation using 6-0 and 7-0 polypropylene with 30- and 32-gauge needles respectively was performed in 5 patients. MAIN OUTCOME MEASURES: Flanged suture disinsertion force in cadaveric sclera. RESULTS: The average force to disinsert a flange created by melting 1.0mm of 5-0, 6-0, 7-0 and 8-0 polypropylene suture from human cadaveric sclera via 27-, 30-, 32- and 33-gauge needle sclerotomies was 3.0 {\textpm} 0.5N, 2.1 {\textpm} 0.3N, 0.9 {\textpm} 0.2N and 0.4 {\textpm} 0.1N respectively. The disinsertion forces for flanges formed by melting 0.5mm of the same gauges were 72-79\% lower (p \&lt; 0.001). In comparison, the breaking strengths of 9-0 and 10-0 polypropylene were 1.0 {\textpm} 0.2N and 0.5 {\textpm} 0.0N. Belt-loop fixation using 6-0 and 7-0 polypropylene with 30- and 32-gauge sclerotomies demonstrated good outcomes at 6 months. CONCLUSIONS: The flanged belt-loop technique is a biomechanically sound method of scleral fixation using 1.0mm flanges of 5-0 to 7-0 polypropylene paired with 27-, 30- and 32- gauge sclerotomies. In contrast, 8-0 polypropylene and 0.5 mm flanges of any suture gauge will likely be unstable with this technique.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.04.017},
	author = {Yuan, Amy and Ma, Kevin and Sharifi, Sina and Pineda, Roberto}
}
@article {1798416,
	title = {Long-Term Risk and Prediction of Progression in Primary Angle Closure Suspect},
	journal = {JAMA Ophthalmol},
	volume = {142},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {216-223},
	abstract = {IMPORTANCE: Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS. OBJECTIVE: To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC). DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up. RESULTS: The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84\%]). By the 14-year follow-up visit, 93 eyes (25\%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95\% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95\% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95\% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 μm from the scleral spur (OR, 0.86 [95\% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 μm from the scleral spur (OR, 0.93 [95\% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 μm (OR, 0.89 [95\% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95\% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model{\textquoteright}s performance. CONCLUSIONS AND RELEVANCE: This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 μm and light-room ARA at 750 μm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.},
	keywords = {Child, Preschool, Cohort Studies, Female, Glaucoma, Angle-Closure, Humans, Intraocular Pressure, Iridectomy, Iris, Tomography, Optical Coherence},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.5286},
	author = {Yuan, Yixiong and Xiong, Ruilin and Wang, Wei and Xu, Benjamin Y and Liao, Chimei and Yang, Shaopeng and Li, Cong and Zhang, Jian and Yin, Qiuxia and Zheng, Yingfeng and Friedman, David S and Foster, Paul J and He, Mingguang}
}
@article {1688356,
	title = {Fourteen-Year Outcome of Angle-Closure Prevention with Laser Iridotomy in the Zhongshan Angle-Closure Prevention Study: Extended Follow-up of a Randomized Controlled Trial},
	journal = {Ophthalmology},
	volume = {130},
	number = {8},
	year = {2023},
	month = {2023 Aug},
	pages = {786-794},
	abstract = {PURPOSE: This study aimed to evaluate the efficacy of laser peripheral iridotomy (LPI) prophylaxis for patients with primary angle-closure suspect (PACS) after 14 years and to identify risk factors for the conversion from PACS to primary angle closure (PAC). DESIGN: Extended follow-up of the Zhongshan Angle-Closure Prevention Study. PARTICIPANTS: Eight hundred eighty-nine Chinese patients 50 to 70 years of age with bilateral PACS. METHODS: Each patient received LPI in 1 randomly selected eye, with the fellow untreated eye serving as a control. Because the risk of glaucoma was low and acute angle closure (AAC) occurred only rarely, the follow-up was extended to 14 years despite substantial benefits of LPI reported after the 6-year visit. MAIN OUTCOME MEASURES: Incidence of PAC, a composite end point including peripheral anterior synechiae, intraocular pressure (IOP) of \&gt; 24 mmHg, or AAC. RESULTS: During the 14 years, 390 LPI-treated eyes and 388 control eyes were lost to follow-up. A total of 33 LPI-treated eyes and 105 control eyes reached primary end points (P \&lt; 0.01). Within them, 1 LPI-treated eye and 5 control eyes progressed to AAC. Primary angle-closure glaucoma was found in 2 LPI-treated eyes and 4 control eyes. The hazard ratio for progression to PAC was 0.31 (95\% confidence interval, 0.21-0.46) in LPI-treated eyes compared with control eyes. At the 14-year visit, LPI-treated eyes showed more severe nuclear cataract, higher IOP, and larger angle width and limbal anterior chamber depth (LACD) than control eyes. Higher IOP, shallower LACD, and greater central anterior chamber depth (CACD) were associated with an increased risk of end points developing in control eyes. In the treated group, eyes with higher IOP, shallower LACD, or less IOP elevation after the darkroom prone provocative test (DRPPT) were more likely to demonstrate PAC after LPI. CONCLUIONS: Despite a two-third decrease in PAC occurrence after LPI, the cumulative risk of progression was relatively low in the community-based PACS population over 14 years. Apart from IOP, IOP elevation after DRPPT, CACD, and LACD, more risk factors are needed to achieve precise prediction of PAC occurrence and to guide clinical practice. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
	keywords = {Acute Disease, Eye Abnormalities, Follow-Up Studies, Glaucoma, Glaucoma, Angle-Closure, Gonioscopy, Humans, Intraocular Pressure, Iridectomy, Iris, Laser Therapy, Lasers, Treatment Outcome},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2023.03.024},
	author = {Yuan, Yixiong and Wang, Wei and Xiong, Ruilin and Zhang, Jian and Li, Cong and Yang, Shaopeng and Friedman, David S and Foster, Paul J and He, Mingguang}
}
@article {1608606,
	title = {An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates},
	journal = {Cell Host Microbe},
	volume = {29},
	number = {9},
	year = {2021},
	month = {2021 09 08},
	pages = {1437-1453.e8},
	abstract = {The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T\&nbsp;cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale.},
	keywords = {Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Vaccines, Dependovirus, Female, Humans, Immunogenicity, Vaccine, Immunologic Memory, Macaca fascicularis, Macaca mulatta, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, SARS-CoV-2, Spike Glycoprotein, Coronavirus, T-Lymphocytes, Transgenes, Vaccination, Viral Load},
	issn = {1934-6069},
	doi = {10.1016/j.chom.2021.08.002},
	author = {Zabaleta, Nerea and Dai, Wenlong and Bhatt, Urja and H{\'e}rate, C{\'e}cile and Maisonnasse, Pauline and Chichester, Jessica A and Sanmiguel, Julio and Estelien, Reynette and Michalson, Kristofer T and Diop, Cheikh and Maciorowski, Dawid and Dereuddre-Bosquet, Nathalie and Cavarelli, Mariangela and Gallou{\"e}t, Anne-Sophie and Naninck, Thibaut and Kahlaoui, Nidhal and Lemaitre, Julien and Qi, Wenbin and Hudspeth, Elissa and Cucalon, Allison and Dyer, Cecilia D and Pampena, M Betina and Knox, James J and LaRocque, Regina C and Charles, Richelle C and Dan Li and Kim, Maya and Sheridan, Abigail and Storm, Nadia and Johnson, Rebecca I and Feldman, Jared and Hauser, Blake M and Contreras, Vanessa and Marlin, Romain and Tsong Fang, Rapha{\"e}l Ho and Chapon, Catherine and van der Werf, Sylvie and Zinn, Eric and Ryan, Aisling and Kobayashi, Dione T and Chauhan, Ruchi and McGlynn, Marion and Ryan, Edward T and Schmidt, Aaron G and Price, Brian and Honko, Anna and Griffiths, Anthony and Yaghmour, Sam and Hodge, Robert and Betts, Michael R and Freeman, Mason W and Wilson, James M and Le Grand, Roger and Vandenberghe, Luk H}
}
@article {1642031,
	title = {Durable immunogenicity, adaptation to emerging variants, and low-dose efficacy of an AAV-based COVID-19 vaccine platform in macaques},
	journal = {Mol Ther},
	volume = {30},
	number = {9},
	year = {2022},
	month = {2022 09 07},
	pages = {2952-2967},
	abstract = {The COVID-19 pandemic continues to have devastating consequences on health and economy, even after the approval of safe and effective vaccines. Waning immunity, the emergence of variants of concern, breakthrough infections, and lack of global vaccine access and acceptance perpetuate the epidemic. Here, we demonstrate that a single injection of an adenoassociated virus (AAV)-based COVID-19 vaccine elicits at least 17-month-long neutralizing antibody responses in non-human primates at levels that were previously shown to protect from viral challenge. To improve the scalability of this durable vaccine candidate, we further optimized the vector design for greater potency at a reduced dose in mice and non-human primates. Finally, we show that the platform can be rapidly adapted to other variants of concern to robustly maintain immunogenicity and protect from challenge. In summary, we demonstrate this class of AAV can provide durable immunogenicity, provide protection at dose that is low and scalable, and be adapted readily to novel emerging vaccine antigens thus may provide a potent tool in the ongoing fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).},
	keywords = {Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Vaccines, Dependovirus, Humans, Macaca, Mice, Pandemics, SARS-CoV-2, Viral Vaccines},
	issn = {1525-0024},
	doi = {10.1016/j.ymthe.2022.05.007},
	author = {Zabaleta, Nerea and Bhatt, Urja and H{\'e}rate, C{\'e}cile and Maisonnasse, Pauline and Sanmiguel, Julio and Diop, Cheikh and Castore, Sofia and Estelien, Reynette and Dan Li and Dereuddre-Bosquet, Nathalie and Cavarelli, Mariangela and Gallou{\"e}t, Anne-Sophie and Pascal, Quentin and Naninck, Thibaut and Kahlaoui, Nidhal and Lemaitre, Julien and Relouzat, Francis and Ronzitti, Giuseppe and Thibaut, Hendrik Jan and Montomoli, Emanuele and Wilson, James M and Le Grand, Roger and Vandenberghe, Luk H}
}
@article {647361,
	title = {Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions.},
	journal = {Nat Commun},
	volume = {7},
	year = {2016},
	month = {2016},
	pages = {10363},
	abstract = {Endomucin is a membrane-bound glycoprotein expressed luminally by endothelial cells that line postcapillary venules, a primary site of leukocyte recruitment during inflammation. Here we show that endomucin abrogation on quiescent endothelial cells enables neutrophils to adhere firmly, via LFA-1-mediated binding to ICAM-1 constitutively expressed by endothelial cells. Moreover, TNF-α stimulation downregulates cell surface expression of endomucin concurrent with increased expression of adhesion molecules. Adenovirus-mediated expression of endomucin under inflammatory conditions prevents neutrophil adhesion in vitro and reduces the infiltration of CD45(+) and NIMP-R14(+) cells in vivo. These results indicate that endomucin prevents leukocyte contact with adhesion molecules in non-inflamed tissues and that downregulation of endomucin is critical to facilitate adhesion of leukocytes into inflamed tissues.},
	issn = {2041-1723},
	doi = {10.1038/ncomms10363},
	author = {Zahr, Alisar and Alcaide, Pilar and Yang, Jinling and Jones, Alexander and Gregory, Meredith and Dela Paz, Nathaniel G and Patel-Hett, Sunita and Nevers, Tania and Koirala, Adarsha and Luscinskas, Francis W and Saint-Geniez, Magali and Ksander, Bruce and D{\textquoteright}Amore, Patricia A and Arg{\"u}eso, Pablo}
}
@article {1798366,
	title = {SARS-CoV-2 variant biology and immune evasion},
	journal = {Prog Mol Biol Transl Sci},
	volume = {202},
	year = {2024},
	month = {2024},
	pages = {45-66},
	abstract = {This chapter discusses the SARS-CoV-2 variants and their immune evasion strategies, shedding light on the dynamic nature of the COVID-19 pandemic. The ecological dynamics and viral evolution of SARS-CoV-2 are explored, considering carriers of infection, individual immunity profiles, and human movement as key factors in the emergence and dissemination of variants. The chapter discusses SARS-CoV-2 mutation, including mutation rate, substitution rate, and recombination, influencing genetic diversity and evolution. Transmission bottlenecks are highlighted as determinants of dominant variants during viral spread. The evolution phases of the pandemic are outlined, from limited early evolution to the emergence of notable changes like the D614G substitution and variants with heavy mutations. Variants of Concern (VOCs), including Alpha, Beta, Gamma, and the recent Omicron variant, are examined, with insights into inter-lineage and intra-lineage dynamics. The origin of VOCs and the Omicron variant is explored, alongside the role of the furin cleavage site (FCS) in variant emergence. The impact of structural and non-structural proteins on viral infectivity is assessed, as well as innate immunity evasion strategies employed by SARS-CoV-2 variants. The chapter concludes by considering future possibilities, including ongoing virus evolution, the need for surveillance, vaccine development, and public health measures.},
	keywords = {Biology, COVID-19, Humans, Immune Evasion, Mutation, Pandemics, SARS-CoV-2},
	issn = {1878-0814},
	doi = {10.1016/bs.pmbts.2023.11.007},
	author = {Zaidi, Asiya Kamber and Singh, Rohan Bir}
}
@article {1798351,
	title = {COVID-19 pathogenesis},
	journal = {Prog Mol Biol Transl Sci},
	volume = {202},
	year = {2024},
	month = {2024},
	pages = {67-112},
	abstract = {The pathogenesis of COVID-19 involves a complex interplay between host factors and the SARS-CoV-2 virus, leading to a multitude of clinical manifestations beyond the respiratory system. This chapter provides an overview of the risk factors, genetic predisposition, and multisystem manifestations of COVID-19, shedding light on the underlying mechanisms that contribute to extrapulmonary manifestations. The chapter discusses the direct invasion of SARS-CoV-2 into various organs as well as the indirect mechanisms such as dysregulation of the renin-angiotensin-aldosterone system (RAAS), immune response dysfunctions within the innate and adaptive immune systems, endothelial damage, and immunothrombosis. Furthermore, the multisystem manifestations of COVID-19 across different organ systems, including the cardiovascular, renal, gastrointestinal, hepatobiliary, nervous, endocrine and metabolic, ophthalmic, ear-nose-throat, reproductive, hematopoietic, and immune systems are discussed in detail. Each system exhibits unique manifestations that contribute to the complexity of the disease.},
	keywords = {COVID-19, Humans, Immune System, Renin-Angiotensin System, Risk Factors, SARS-CoV-2},
	issn = {1878-0814},
	doi = {10.1016/bs.pmbts.2023.07.001},
	author = {Zaidi, Asiya Kamber and Singh, Rohan Bir and A A Rizvi, Syed and Dehgani-Mobaraki, Puya and Palladino, Nicola}
}
@article {1798356,
	title = {Epidemiology of COVID-19},
	journal = {Prog Mol Biol Transl Sci},
	volume = {202},
	year = {2024},
	month = {2024},
	pages = {25-38},
	abstract = {This chapter provides a detailed exploration of the epidemiology of COVID-19, focusing on several key aspects that offer valuable insights into the disease progression. A comprehensive comparison is made between the three related coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2, elucidating their similarities and differences in terms of transmission dynamics, clinical presentation, laboratory and radiological findings, infection mechanisms, and mortality rates. The concept of herd immunity is then discussed, exploring its relevance and potential implications for controlling the spread of COVID-19. Next, the chapter delves into the changing epidemiology of the disease, examining how various factors such as human behavior, public health interventions, and viral mutations have influenced its transmission patterns and severity over time. Finally, the timelines and evolution of COVID-19 are outlined, tracing the origins of the virus, its rapid global spread, and the emergence of new variants.},
	keywords = {COVID-19, Humans, Middle East Respiratory Syndrome Coronavirus, Public Health, SARS-CoV-2},
	issn = {1878-0814},
	doi = {10.1016/bs.pmbts.2023.09.002},
	author = {Zaidi, Asiya Kamber and Singh, Rohan Bir}
}
@article {1059856,
	title = {Seed Location Impacts Whole-Brain Structural Network Comparisons between Healthy Elderly and Individuals with Alzheimer{\textquoteright}s Disease},
	journal = {Brain Sci},
	volume = {7},
	number = {4},
	year = {2017},
	month = {2017 Apr 06},
	abstract = {Whole-brain networks derived from diffusion tensor imaging (DTI) data require the identification of seed and target regions of interest (ROIs) to assess connectivity patterns. This study investigated how initiating tracts from gray matter (GM) or white matter (WM) seed ROIs impacts (1) structural networks constructed from DTI data from healthy elderly (control) and individuals with Alzheimer{\textquoteright}s disease (AD) and (2) between-group comparisons using these networks. DTI datasets were obtained from the Alzheimer{\textquoteright}s disease Neuroimaging Initiative database. Deterministic tractography was used to build two whole-brain networks for each subject; one in which tracts were initiated from WM ROIs and another in which they were initiated from GM ROIs. With respect to the first goal, in both groups, WM-seeded networks had approximately 400 more connections and stronger connections (as measured by number of streamlines per connection) than GM-seeded networks, but shared 94\% of the connections found in the GM-seed networks. With respect to the second goal, between-group comparisons revealed a stronger subnetwork (as measured by number of streamlines per connection) in controls compared to AD using both WM-seeded and GM-seeded networks. The comparison using WM-seeded networks produced a larger (i.e., a greater number of connections) and more significant subnetwork in controls versus AD. Global, local, and nodal efficiency were greater in controls compared to AD, and between-group comparisons of these measures using WM-seeded networks had larger effect sizes than those using GM-seeded networks. These findings affirm that seed location significantly affects the ability to detect between-group differences in structural networks.},
	doi = {10.3390/brainsci7040037},
	author = {Zajac, Lauren and Koo, Bang-Bon and Bauer, Corinna M and Killiany, Ron and Killiany, Ron}
}
@article {1490454,
	title = {Copy-number variation contributes 9\% of pathogenicity in the inherited retinal degenerations},
	journal = {Genet Med},
	volume = {22},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {1079-1087},
	abstract = {PURPOSE: Current sequencing strategies can genetically solve 55-60\% of inherited retinal degeneration (IRD) cases, despite recent progress in sequencing. This can partially be attributed to elusive pathogenic variants (PVs) in known IRD genes, including copy-number variations (CNVs), which have been shown as major contributors to unsolved IRD cases. METHODS: Five hundred IRD patients were analyzed with targeted next-generation sequencing (NGS). The NGS data were used to detect CNVs with ExomeDepth and gCNV and the results were compared with CNV detection with a single-nucleotide polymorphism (SNP) array. Likely causal CNV predictions were validated by quantitative polymerase chain reaction (qPCR). RESULTS: Likely disease-causing single-nucleotide variants (SNVs) and small indels were found in 55.6\% of subjects. PVs in USH2A (11.6\%), RPGR (4\%), and EYS (4\%) were the most common. Likely causal CNVs were found in an additional 8.8\% of patients. Of the three CNV detection methods, gCNV showed the highest accuracy. Approximately 30\% of unsolved subjects had a single likely PV in a recessive IRD gene. CONCLUSION: CNV detection using NGS-based algorithms is a reliable method that greatly increases the genetic diagnostic rate of IRDs. Experimentally validating CNVs helps estimate the rate at which IRDs might be solved by a CNV plus a more elusive variant.},
	issn = {1530-0366},
	doi = {10.1038/s41436-020-0759-8},
	author = {Zampaglione, Erin and Kinde, Benyam and Place, Emily M and Navarro-Gomez, Daniel and Maher, Matthew and Jamshidi, Farzad and Nassiri, Sherwin and Mazzone, J Alex and Finn, Caitlin and Schlegel, Dana and Comander, Jason and Pierce, Eric A and Bujakowska, Kinga M}
}
@article {1632284,
	title = {The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK)},
	journal = {Genet Med},
	volume = {24},
	number = {2},
	year = {2022},
	month = {2022 Feb},
	pages = {332-343},
	abstract = {PURPOSE: In Mendelian disease diagnosis, variant analysis is a repetitive, error-prone, and time consuming process. To address this, we have developed the Mendelian Analysis Toolkit (MATK), a configurable, automated variant ranking program. METHODS: MATK aggregates variant information from multiple annotation sources and uses expert-designed rules with parameterized weights to produce a ranked list of potentially causal solutions. MATK performance was measured by a comparison between MATK-aided and human-domain expert analyses of 1060 families with inherited retinal degeneration (IRD), analyzed using an IRD-specific gene panel (589 individuals) and exome sequencing (471 families). RESULTS: When comparing MATK-assisted analysis with expert curation in both the IRD-specific gene panel and exome sequencing (1060 subjects), 97.3\% of potential solutions found by experts were also identified by the MATK-assisted analysis (541 solutions identified with MATK of 556 solutions found by conventional analysis). Furthermore, MATK-assisted analysis identified 114 additional potential solutions from the 504 cases unsolved by conventional analysis. CONCLUSION: MATK expedites the process of identification of likely solving variants in Mendelian traits, and reduces variability stemming from human error and researcher bias. MATK facilitates data reanalysis to keep up with the constantly improving annotation sources and next-generation sequencing processing pipelines. The software is open source and available at https://gitlab.com/matthew_maher/mendelanalysis.},
	issn = {1530-0366},
	doi = {10.1016/j.gim.2021.09.015},
	author = {Zampaglione, Erin and Maher, Matthew and Place, Emily M and Wagner, Naomi E and DiTroia, Stephanie and Chao, Katherine R and England, Eleina and Cmg, Broad and Catomeris, Andrew and Nassiri, Sherwin and Himes, Seraphim and Pagliarulo, Joey and Ferguson, Charles and Galdikait{\'e}-Brazien{\'e}, Egl{\'e} and Cole, Brian and Pierce, Eric A and Bujakowska, Kinga M}
}
@article {382461,
	title = {ROCK-Isoform-Specific Polarization of Macrophages Associated with Age-Related Macular Degeneration.},
	journal = {Cell Rep},
	volume = {10},
	number = {7},
	year = {2015},
	month = {2015 Feb 24},
	pages = {1173-86},
	abstract = {Age is a major risk factor in age-related macular degeneration (AMD), but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK) signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2015.01.050},
	author = {Zandi, Souska and Nakao, Shintaro and Chun, Kwang-Hoon and Fiorina, Paolo and Sun, Dawei and Arita, Ryoichi and Zhao, Ming and Kim, Enoch and Schueller, Olivier and Campbell, Stewart and Taher, Mahdi and Melhorn, Mark Ivan and Schering, Alexander and Gatti, Francesca and Tezza, Sara and Xie, Fang and Vergani, Andrea and Yoshida, Shigeo and Ishikawa, Keijiro and Yamaguchi, Muneo and Sasaki, Fumiyuki and Schmidt-Ullrich, Ruth and Hata, Yasuaki and Enaida, Hiroshi and Yuzawa, Mitsuko and Yokomizo, Takehiko and Kim, Young-Bum and Sweetnam, Paul and Ishibashi, Tatsuro and Hafezi-Moghadam, Ali}
}
@article {1782266,
	title = {ASSOCIATION OF DIABETIC MACULAR EDEMA WITH QUALITY OF LIFE IN PATIENTS WITH TYPE 2 DIABETES: The Fushun Diabetic Retinopathy Cohort Study},
	journal = {Retina},
	volume = {44},
	number = {3},
	year = {2024},
	month = {2024 Mar 01},
	pages = {537-544},
	abstract = {PURPOSE: To report the vision-related quality of life in patients with diabetic macular edema (DME) in a population-based study. METHODS: In this cross-sectional study, we analyzed 1,659 subjects with type 2 diabetes. Questionnaires were administered to assess the patient{\textquoteright}s vision-related quality of life. Diabetic macular edema severity was graded according to the established protocols. A subject{\textquoteright}s DME score ranged from 1 (no DME in either eye) to 7 (severe bilateral DME) using predefined criteria. RESULTS: Composite 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores for participants with DME were 88.9 (interquartile range [IQR]: 76.2-94.9) compared with 92.0 (IQR: 82.7-96.0) for those without DME ( P \&lt; 0.001). Locally weighted scatterplot smoothing plots depicted a consistent decline in composite NEI-VFQ-25 scores corresponding to the escalation of bilateral DME severity: starting from 88.59 for no DME in either eye, progressing through 86.65, 85.83, 85.31, 84.91, 83.85, and culminating at 82.71 for bilateral severe DME. Notably, the locally weighted scatterplot smoothing plots highlighted significant NEI-VFQ-25 composite score reduction at unilateral mild DME (slope m = -1.94). CONCLUSION: Significant changes in vision-related quality of life manifest in the early stage of DME. Therefore, early identification and intervention for these patients are crucial clinical objectives.},
	keywords = {Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Humans, Macular Edema, Quality of Life, Surveys and Questionnaires, Visual Acuity},
	issn = {1539-2864},
	doi = {10.1097/IAE.0000000000003992},
	author = {Zang, Bo and Rong, Shi Song and Wang, Yu and Feng, Ke Mi and Ding, Xiao Xia and Wen, Liang and Zang, Dongxiao and Li, Dong and Liang, Yuan Bo and Wang, Feng Hua and Zhai, Gang}
}
@article {1655710,
	title = {[The impact of diabetic retinopathy on vision-related quality of life]},
	journal = {Zhonghua Yan Ke Za Zhi},
	volume = {58},
	number = {10},
	year = {2022},
	month = {2022 Oct 11},
	pages = {760-768},
	abstract = {Objective: To assess the effect of diabetic retinopathy (DR) on vision-related quality of life (VRQoL) in patients with type 2 diabetes. Methods: In this cross-sectional study, patients with type 2 diabetes residing in 15 residency communities in Fushun, Liaoning province were enrolled from July 2012 to May 2013. We measured the VRQoL by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). Patients were grouped according to their age, gender, presence of visual impairment, and affected eyes. NEI-VFQ-25 scores were compared between/among groups using the Wilcoxon rank-sum test or Kruskal-Wallis H test. The severity of DR in the eyes was graded into no DR, mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR). Severity scores from both eyes were then summarized to create a single per-person grade ranging from 1 (no DR in either eye) to 7 (bilateral PDR). Generalized linear models were used to assess the linear relationship between NEI-VFQ-25 scores and DR severity. Locally weighted scatterplot smoothing plots were generated to evaluate the possible nonlinear associations between concatenated severity of DR and VRQoL. Results: A total of 1 537 patients were recruited, including 836 (54.4\%) with no DR, 479 (31.2\%) with mild NPDR, 90 (5.9\%) with moderate NPDR, 72 (4.7\%) with severe NPDR and 60 (3.9\%) with PDR. Compared with patients with unilateral DR, bilaterally involved subjects were statistically significantly compromised in general vision [70.2 (66.5, 72.5) vs. 68.9 (63.9, 71.6), Z=90.222, P=0.038], near activities [90.5 (85.8, 94.0) vs. 88.8 (84.5, 92.5), Z=114.942, P=0.005], dependency [91.1 (85.6, 96.5) vs. 89.3 (83.8, 94.5), Z=91.934, P=0.033], mental health [80.0 (73.4, 84.9) vs. 77.5 (70.8, 82.0), Z=118.388, P=0.003], role difficulties [76.8 (70.1, 82.4) vs. 74.5 (67.6, 80.6), Z =90.791, P=0.036] and NEI-VFQ-25 composite [88.3 (84.2, 91.0) vs. 86.9 (82.8, 90.1), Z=96.207, P=0.024]. Scores on general vision (χ2=85.665), near activities (χ2=78.462), distance activities (χ2=145.489), social function (χ2=53.629), dependency (χ2=86.710), mental health (χ2=68.281), role difficulties (χ2=45.357), color vision (χ2=68.176), peripheral vision (χ2=116.179) and NEI-VFQ-25 composite (χ2=133.291) decreased gradually as DR severity increased (all P\&lt;0.001). On role difficulties, locally weighted scatterplot smoothing plots showed significant"turning points"from bilateral mild NPDR to mild NPDR/\&gt;mild NPDR (slope m=-4.7) and from moderate NPDR/>=moderate NPDR to severe NPDR/>=severe NPDR (slope m=-12.6). Conclusion: Both greater severity and bilaterality of DR were associated with lower vision-specific VRQoL, particularly role difficulties and mental health.},
	keywords = {Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Humans, Quality of Life, Surveys and Questionnaires, Visual Acuity},
	issn = {0412-4081},
	doi = {10.3760/cma.j.cn112142-20211210-00581},
	author = {Zang, B and Rong, S S and Ding, X X and Zou, B and Zang, D X and Wang, Y. and Xu, K M and D Feng and Li, Dong}
}
@article {1470969,
	title = {Effects of cannabis and its components on the retina: a systematic review},
	journal = {Cutan Ocul Toxicol},
	volume = {39},
	number = {1},
	year = {2020},
	month = {2020 Mar},
	pages = {1-9},
	abstract = {Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina. We searched five online databases for the combined terms for outcome ("retina") and exposure ("cannabis"). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed. We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects. This review suggests that cannabinoids may have an important role in retinal processing and function.},
	issn = {1556-9535},
	doi = {10.1080/15569527.2019.1685534},
	author = {Zantut, Paulo R A and Veras, Mariana M and Yariwake, Victor Y and Takahashi, Walter Y and Saldiva, Paulo H and Young, Lucy H and Damico, Francisco Max and Fajersztajn, La{\'\i}s}
}
@article {913561,
	title = {Human Corneal Fibroblast Pattern Evolution and Matrix Synthesis on Mechanically Biased Substrates.},
	journal = {Tissue Eng Part A},
	volume = {22},
	number = {19-20},
	year = {2016},
	month = {2016 Oct},
	pages = {1204-1217},
	abstract = {In a fibroblast colony model of corneal stromal development, we asked how physiological tension influences the patterning dynamics of fibroblasts and the orientation of deposited extracellular matrix (ECM). Using long-term live-cell microscopy, enabled by an optically accessible mechanobioreactor, a primary human corneal fibroblast colony was cultured on three types of substrates: a mechanically biased, loaded, dense, disorganized collagen substrate (LDDCS), a glass coverslip, and an unloaded, dense, disorganized collagen substrate (UDDCS). On LDDCS, fibroblast orientation and migration along a preferred angle developed early, cell orientation was correlated over long distances, and the colony pattern was stable. On glass, fibroblast orientation was poorly correlated, developed more slowly, and colony patterns were metastable. On UDDCS, cell orientation was correlated over shorter distances compared with LDDCS specimens. On all substrates, the ECM pattern reflected the cell pattern. In summary, mechanically biasing the collagen substrate altered the early migration behavior of individual cells, leading to stable emergent cell patterning, which set the template for newly synthesized ECM.},
	issn = {1937-335X},
	doi = {10.1089/ten.TEA.2016.0164},
	author = {Zareian, Ramin and Susilo, Monica E and Paten, Jeffrey A and McLean, James P and Hollmann, Joseph and Karamichos, Dimitrios and Messer, Conor S and Tambe, Dhananjay T. and Saeidi, Nima and Zieske, James D and Ruberti, Jeffrey W}
}
@article {1586157,
	title = {Characteristics of p.Gln368Ter Myocilin Variant and Influence of Polygenic Risk on Glaucoma Penetrance in the UK Biobank},
	journal = {Ophthalmology},
	volume = {128},
	number = {9},
	year = {2021},
	month = {2021 Sep},
	pages = {1300-1311},
	abstract = {PURPOSE: MYOC (myocilin) mutations account for 3\% to 5\% of primary open-angle glaucoma (POAG) cases. We aimed to understand the true population-wide penetrance and characteristics of glaucoma among individuals with the most common MYOC variant (p.Gln368Ter) and the impact of a POAG polygenic risk score (PRS) in this population. DESIGN: Cross-sectional population-based study. PARTICIPANTS: Individuals with the p.Gln368Ter variant among 77 959 UK Biobank participants with fundus photographs (FPs). METHODS: A genome-wide POAG PRS was computed, and 2 masked graders reviewed FPs for disc-defined glaucoma (DDG). MAIN OUTCOME MEASURES: Penetrance of glaucoma. RESULTS: Two hundred individuals carried the p.Gln368Ter heterozygous genotype, and 177 had gradable FPs. One hundred thirty-two showed no evidence of glaucoma, 45 (25.4\%) had probable/definite glaucoma in at least 1 eye, and 19 (10.7\%) had bilateral glaucoma. No differences were found in age, race/ethnicity, or gender among groups (P \&gt; 0.05). Of those with DDG, 31\% self-reported or had International Classification of Diseases codes for glaucoma, whereas 69\% were undiagnosed. Those with DDG had higher medication-adjusted cornea-corrected intraocular pressure (IOPcc) (P \&lt; 0.001) vs. those without glaucoma. This difference in IOPcc was larger in those with DDG with a prior glaucoma diagnosis versus those not diagnosed (P \&lt; 0.001). Most p.Gln368Ter carriers showed IOP in the normal range (<=21 mmHg), although this proportion was lower in those with DDG (P \&lt; 0.02) and those with prior glaucoma diagnosis (P \&lt; 0.03). Prevalence of DDG increased with each decile of POAG PRS. Individuals with DDG demonstrated significantly higher PRS compared with those without glaucoma (0.37 {\textpm} 0.97 vs. 0.01 {\textpm} 0.90; P\&nbsp;= 0.03). Of those with DDG, individuals with a prior diagnosis of glaucoma had higher PRS compared with undiagnosed individuals (1.31 {\textpm} 0.64 vs. 0.00 {\textpm} 0.81; P \&lt; 0.001) and 27.5 times (95\% confidence interval, 2.5-306.6) adjusted odds of being in the top decile of PRS for POAG. CONCLUSIONS: One in 4 individuals with the MYOC p.Gln368Ter mutation demonstrated evidence of glaucoma, a substantially higher penetrance than previously estimated, with 69\% of cases undetected. A large portion of p.Gln368Ter carriers, including those with DDG, have IOP in the normal range, despite similar age. Polygenic risk score increases disease penetrance and severity, supporting the usefulness of PRS in risk stratification among MYOC p.Gln368Ter carriers.},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2021.03.007},
	author = {Zebardast, Nazlee and Sekimitsu, Sayuri and Wang, Jiali and Tobias Elze and Gharahkhani, Puya and Cole, Brian S and Lin, Michael M and Segr{\`e}, Ayellet V and Wiggs, Janey L and International Glaucoma Genetics Consortium}
}
@article {1798341,
	title = {Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy},
	journal = {Genet Med},
	year = {2024},
	month = {2024 Jan 28},
	pages = {101081},
	abstract = {PURPOSE: Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian descent with only few reports of North African descent.

METHODS: Genome, targeted next-generation, and Sanger sequencing was applied to cohort of \~{}4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium cells, and zebrafish. Variants{\textquoteright} pathogenicity was accessed using 3D-modeling and/or ROs.

RESULTS: Here, we identified a novel gene defect with three distinct pathogenic variants in UBAP1L in 4 independent autosomal recessive IRD cases from Tunisia. UBAP1L is expressed in the retinal pigment epithelium and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin-associated domain, predicted to interact with ubiquitin. In silico and in~vitro studies, including 3D-modeling and ROs revealed that the solenoid of overlapping ubiquitin-associated domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein.

CONCLUSION: Biallelic UBAP1L variants are a novel cause of IRDs, most likely enriched in the North African population.},
	issn = {1530-0366},
	doi = {10.1016/j.gim.2024.101081},
	author = {Zeitz, Christina and Navarro, Julien and Azizzadeh Pormehr, Leila and M{\'e}j{\'e}case, C{\'e}cile and Neves, Luiza M and Letellier, Camille and Condroyer, Christel and Albadri, Shahad and Amprou, Andr{\'e}a and Antonio, Aline and Ben-Yacoub, Tasnim and Wohlschlegel, Juliette and Andrieu, Camille and Serafini, Malo and Bianco, Lorenzo and Antropoli, Alessio and Nassisi, Marco and El Shamieh, Said and Chantot-Bastaraud, Sandra and Mohand-Sa{\"\i}d, Saddek and Smirnov, Vasily and Sahel, Jos{\'e}-Alain and Del Bene, Filippo and Audo, Isabelle}
}
@article {1798461,
	title = {Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health},
	journal = {Sci Transl Med},
	volume = {16},
	number = {731},
	year = {2024},
	month = {2024 Jan 24},
	pages = {eadg4517},
	abstract = {The human retina is a multilayered tissue that offers a unique window into systemic health. Optical coherence tomography (OCT) is widely used in eye care and allows the noninvasive, rapid capture of retinal anatomy in exquisite detail. We conducted genotypic and phenotypic analyses of retinal layer thicknesses using macular OCT images from 44,823 UK Biobank participants. We performed OCT layer cross-phenotype association analyses (OCT-XWAS), associating retinal thicknesses with 1866 incident conditions (median 10-year follow-up) and 88 quantitative traits and blood biomarkers. We performed genome-wide association studies (GWASs), identifying inherited genetic markers that influence retinal layer thicknesses and replicated our associations among the LIFE-Adult Study (N = 6313). Last, we performed a comparative analysis of phenome- and genome-wide associations to identify putative causal links between retinal layer thicknesses and both ocular and systemic conditions. Independent associations with incident mortality were detected for thinner photoreceptor segments (PSs) and, separately, ganglion cell complex layers. Phenotypic associations were detected between thinner retinal layers and ocular, neuropsychiatric, cardiometabolic, and pulmonary conditions. A GWAS of retinal layer thicknesses yielded 259 unique loci. Consistency between epidemiologic and genetic associations suggested links between a thinner retinal nerve fiber layer with glaucoma, thinner PS with age-related macular degeneration, and poor cardiometabolic and pulmonary function with a thinner PS. In conclusion, we identified multiple inherited genetic loci and acquired systemic cardio-metabolic-pulmonary conditions associated with thinner retinal layers and identify retinal layers wherein thinning is predictive of future ocular and systemic conditions.},
	keywords = {Adult, Cardiovascular Diseases, Face, Genome-Wide Association Study, Humans, Retina, Tomography, Optical Coherence},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.adg4517},
	author = {Zekavat, Seyedeh Maryam and Doroodgar Jorshery, Saman and Rauscher, Franziska G and Horn, Katrin and Sekimitsu, Sayuri and Koyama, Satoshi and Nguyen, Trang T and Costanzo, Maria C and Jang, Dongkeun and Burtt, No{\"e}l P and K{\"u}hnapfel, Andreas and Shweikh, Yusrah and Ye, Yixuan and Raghu, Vineet and Zhao, Hongyu and Marzyeh Ghassemi and Tobias Elze and Segr{\`e}, Ayellet V and Wiggs, Janey L and Del Priore, Lucian and Scholz, Markus and Wang, Jay C and Natarajan, Pradeep and Zebardast, Nazlee}
}
@article {1632300,
	title = {Photoreceptor Layer Thinning Is an Early Biomarker for Age-Related Macular Degeneration: Epidemiologic and Genetic Evidence from UK Biobank OCT Data},
	journal = {Ophthalmology},
	volume = {129},
	number = {6},
	year = {2022},
	month = {2022 06},
	pages = {694-707},
	abstract = {PURPOSE: Despite widespread use of OCT, an early-stage imaging biomarker for age-related macular degeneration (AMD) has not been identified. Pathophysiologically, the timing of drusen accumulation in relationship to photoreceptor degeneration in AMD remains unclear, as are the inherited genetic variants contributing to these processes. Herein, we jointly analyzed OCT, electronic health record data, and genomic data to characterize the time sequence of changes in retinal layer thicknesses in AMD, as well as epidemiologic and genetic associations between retinal layer thicknesses and AMD. DESIGN: Cohort study. PARTICIPANTS: Forty-four thousand eight hundred twenty-three individuals from the UK Biobank (enrollment age range, 40-70 years; 54\% women; median follow-up, 10 years). METHODS: The Topcon Advanced Boundary Segmentation algorithm was used for retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we associated AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age-squared (age2), sex, smoking status, and principal components of ancestry. MAIN OUTCOME MEASURES: Prevalent and incident AMD. RESULTS: Photoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed, whereas retinal pigment epithelium (RPE) and Bruch{\textquoteright}s membrane (BM) complex thickening started after 57 years of age. Each standard deviation (SD) of PS thinning and RPE-BM complex thickening was associated with incident AMD (PS: hazard ratio [HR], 1.35; 95\% confidence interval [CI], 1.23-1.47; P\&nbsp;= 3.7\&nbsp;{\texttimes} 10-11; RPE-BM complex: HR, 1.14; 95\% CI, 1.06-1.22; P\&nbsp;= 0.00024). The AMD PRS was associated with PS thinning (β, -0.21 SD per twofold genetically increased risk of AMD; 95\% CI, -0.23 to -0.19; P\&nbsp;= 2.8\&nbsp;{\texttimes} 10-74), and its association with RPE-BM complex was U-shaped (thinning with AMD PRS less than the 92nd percentile and thickening with AMD PRS more than the 92nd percentile). The loci with strongest support for genetic correlation were AMD risk-raising variants Complement Factor H (CFH):rs570618-T, CFH:rs10922109-C, and Age-Related Maculopathy Susceptibility 2 (ARMS2)/High-Temperature Requirement Serine Protease 1 (HTRA1):rs3750846-C on PS thinning and SYN3/Tissue Inhibitor of Metalloprotease 3 (TIMP3):rs5754227-T on RPE-BM complex thickening. CONCLUSIONS: Epidemiologically, PS thinning precedes RPE-BM complex thickening by decades and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage biomarker for future AMD development.},
	keywords = {Adult, Aged, Biological Specimen Banks, Biomarkers, Cohort Studies, Female, High-Temperature Requirement A Serine Peptidase 1, Humans, Macular Degeneration, Male, Middle Aged, Retinal Pigment Epithelium, Tomography, Optical Coherence, United Kingdom},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.02.001},
	author = {Zekavat, Seyedeh Maryam and Sekimitsu, Sayuri and Ye, Yixuan and Raghu, Vineet and Zhao, Hongyu and Tobias Elze and Segr{\`e}, Ayellet V and Wiggs, Janey L and Natarajan, Pradeep and Del Priore, Lucian and Zebardast, Nazlee and Wang, Jay C}
}
@article {1664958,
	title = {Reply},
	journal = {Ophthalmology},
	volume = {130},
	number = {4},
	year = {2023},
	month = {2023 Apr},
	pages = {e15-e16},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.12.003},
	author = {Zekavat, Seyedeh Maryam and Sekimitsu, Sayuri and Doroodgar Jorshery, Saman and Natarajan, Pradeep and Rossin, Elizabeth J and Del Priore, Lucian and Zebardast, Nazlee and Wang, Jay C}
}
@article {1623350,
	title = {Deep Learning of the Retina Enables Phenome- and Genome-Wide Analyses of the Microvasculature},
	journal = {Circulation},
	volume = {145},
	number = {2},
	year = {2022},
	month = {2022 Jan 11},
	pages = {134-150},
	abstract = {BACKGROUND: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. METHODS: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases-based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. RESULTS: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). CONCLUSIONS: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.},
	issn = {1524-4539},
	doi = {10.1161/CIRCULATIONAHA.121.057709},
	author = {Zekavat, Seyedeh Maryam and Raghu, Vineet K and Trinder, Mark and Ye, Yixuan and Koyama, Satoshi and Honigberg, Michael C and Yu, Zhi and Pampana, Akhil and Urbut, Sarah and Haidermota, Sara and O{\textquoteright}Regan, Declan P and Zhao, Hongyu and Ellinor, Patrick T and Segr{\`e}, Ayellet V and Tobias Elze and Wiggs, Janey L and Martone, James and Adelman, Ron A and Zebardast, Nazlee and Del Priore, Lucian and Wang, Jay C and Natarajan, Pradeep}
}
@article {1698381,
	title = {Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank},
	journal = {Nat Commun},
	volume = {14},
	number = {1},
	year = {2023},
	month = {2023 May 19},
	pages = {2860},
	abstract = {Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the etiology of this multifactorial disease is poorly understood. We aimed to identify plasma metabolites associated with the risk of developing POAG in a case-control study (599 cases and 599 matched controls) nested within the Nurses{\textquoteright} Health Studies, and Health Professionals{\textquoteright} Follow-Up Study. Plasma metabolites were measured with LC-MS/MS at the Broad Institute (Cambridge, MA, USA); 369 metabolites from 18 metabolite classes passed quality control analyses. For comparison, in a cross-sectional study in the UK Biobank, 168 metabolites were measured in plasma samples from 2,238 prevalent glaucoma cases and 44,723 controls using NMR spectroscopy (Nightingale, Finland; version 2020). Here we show higher levels of diglycerides and triglycerides are adversely associated with glaucoma in all four cohorts, suggesting that they play an important role in glaucoma pathogenesis.},
	keywords = {Biological Specimen Banks, Case-Control Studies, Chromatography, Liquid, Cross-Sectional Studies, Follow-Up Studies, Glaucoma, Open-Angle, Humans, Tandem Mass Spectrometry, United Kingdom},
	issn = {2041-1723},
	doi = {10.1038/s41467-023-38466-w},
	author = {Zeleznik, Oana A and Kang, Jae H and Lasky-Su, Jessica and Eliassen, A Heather and Frueh, Lisa and Clish, Clary B and Rosner, Bernard A and Tobias Elze and Hysi, Pirro and Khawaja, Anthony and Wiggs, Janey L and Pasquale, Louis R and UK Biobank Eye and Vision Consortium}
}
@article {1645465,
	title = {Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {260},
	number = {11},
	year = {2022},
	month = {2022 Nov},
	pages = {3505-3515},
	abstract = {PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3\&nbsp;mm {\texttimes} 3\&nbsp;mm and 6\&nbsp;mm {\texttimes} 6\&nbsp;mm centered on both the fovea and optic disk. A second 6\&nbsp;mm {\texttimes} 6\&nbsp;mm scan was taken after a 30\&nbsp;s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6\&nbsp;mm {\texttimes} 6\&nbsp;mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD ({\ss} =  - 0.029, p = 0.012), VSD ({\ss} =  - 0.004, p = 0.043) and the choriocapillaris VD ({\ss} =  - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP ({\ss} =  - 0.012, p = 0.013) and choriocapillaris ({\ss} =  - 0.009, p = 0.030). In the 3\&nbsp;mm {\texttimes} 3\&nbsp;mm angiogram centered on optic disk, SCP VDI ({\ss} =  - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP ({\ss} =  - 0.034, p = 0.032; {\ss} =  - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes ({\ss} = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.},
	keywords = {Cross-Sectional Studies, Fluorescein Angiography, Fovea Centralis, Humans, Hypertension, Microvessels, Retinal Vessels, Tomography, Optical Coherence},
	issn = {1435-702X},
	doi = {10.1007/s00417-022-05706-6},
	author = {Zeng, Rebecca and Garg, Itika and Bannai, Deepthi and Kasetty, Megan and Katz, Raviv and Park, Jeayoung and Lizano, Paulo and Miller, John B}
}
@article {1635655,
	title = {Complete Resolution of Central Soft Drusen without Geographic Atrophy or Choroidal Neovascularization},
	journal = {J Clin Med},
	volume = {11},
	number = {6},
	year = {2022},
	month = {2022 Mar 16},
	abstract = {The treatment and prevention of dry age-related macular degeneration (AMD) traditionally involve lifestyle modifications and antioxidant supplementation, including the AREDS2 formula. We present a case of a woman with dry AMD in her right eye with several large, confluent central drusen on her exam and optical coherence tomography B-scan. Over the course of a year, the drusen almost completely disappeared, but the retinal layers were preserved without the development of geographic atrophy or choroidal neovascularization. While the exact cause of this phenomenon is unclear, it was thought to be associated with this patient{\textquoteright}s strict daily use of numerous dietary supplements. This case highlights the potential in exploring alternative medicine supplements in the treatment of AMD.},
	issn = {2077-0383},
	doi = {10.3390/jcm11061637},
	author = {Zeng, Rebecca and Garg, Itika and Miller, John B}
}
@article {959496,
	title = {Genome Sequence of a Cynomolgus Macaque Adenovirus (CynAdV-1) Isolate from a Primate Colony in the United Kingdom.},
	journal = {Genome Announc},
	volume = {4},
	number = {6},
	year = {2016},
	month = {2016 Nov 03},
	abstract = {The genome sequence of a simian adenovirus from a cynomolgus macaque, denoted CynAdV-1, is presented here. Phylogenetic analysis supports CynAdV-1 in an independent clade, comprising a new simian adenovirus (SAdV) species. These genome data are critical for understanding the evolution and relationships of primate adenoviruses, including zoonosis and emergent human pathogens.},
	doi = {10.1128/genomeA.01193-16},
	author = {Zeng, Zhiwei and Zhang, Jing and Jing, Shuping and Cheng, Zetao and Bofill-Mas, Silvia and Maluquer de Motes, Carlos and Hundesa, Ayalkibet and Girones, Rosina and Seto, Donald and Zhang, Qiwei}
}
@article {1653601,
	title = {Structure-function association between contrast sensitivity and retinal thickness (total, regional, and individual retinal layer) in patients with idiopathic epiretinal membrane},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {261},
	number = {3},
	year = {2023},
	month = {2023 Mar},
	pages = {631-639},
	abstract = {PURPOSE: To investigate structure-function associations between retinal thickness, visual acuity (VA), and contrast sensitivity (CS), using the quantitative contrast sensitivity function (qCSF) method in patients with idiopathic epiretinal membrane (ERM). METHODS: Retrospective, cross-sectional observational study. Patients with a diagnosis of idiopathic ERM were included. Patients underwent complete ophthalmic examination, spectral-domain optical coherence tomography imaging (SD-OCT) (SPECTRALIS{\textregistered} Heidelberg), and CS testing using the qCSF method. Outcomes included area under the log CSF (AULCSF), contrast acuity (CA), and CS thresholds at 1, 1.5, 3, 6, 12, and 18 cycles per degree (cpd). RESULTS: A total of 102 eyes of 79 patients were included. Comparing standardized regression coefficients, retinal thickness in most ETDRS sectors was associated with larger reductions in AULCSF, CA, and CS thresholds at 3 and 6\&nbsp;cpd than those in logMAR VA. These differences in effect on VA and CS metrics were more pronounced in the central subfield and inner ETDRS sectors. Among the retinal layers, increased INL thickness had the most detrimental effect on visual function, being significantly associated with reductions in logMAR VA, AULCSF, CA, and CS thresholds at 3 and 6\&nbsp;cpd (all p \&lt; .01), as well as at 1.5 and 12\&nbsp;cpd (p \&lt; .05). CONCLUSION: Retinal thickness seems to be associated with larger reductions in contrast sensitivity than VA in patients with ERM. Measured with the qCSF method, contrast sensitivity may serve as a valuable adjunct visual function metric for patients with ERM.},
	keywords = {Contrast Sensitivity, Cross-Sectional Studies, Epiretinal Membrane, Humans, Retina, Retrospective Studies},
	issn = {1435-702X},
	doi = {10.1007/s00417-022-05819-y},
	author = {Zeng, Rebecca and Vingopoulos, Filippos and Wang, Mengyu and Bannerman, Augustine and Wescott, Hannah E and Baldwin, Grace and Katz, Raviv and Koch, Thomas and Tobias Elze and Kim, Leo A and Vavvas, Demetrios G and Husain, Deeba and Miller, John B}
}
@article {1402592,
	title = {Resolution of fluoroquinolone-resistant keratitis with a PROSE device for enhanced targeted antibiotic delivery},
	journal = {Am J Ophthalmol Case Rep},
	volume = {12},
	year = {2018},
	month = {2018 Dec},
	pages = {73-75},
	abstract = {Purpose: To report the resolution of a fluoroquinolone-resistant keratitis with use of a prosthetic replacement of the ocular surface ecosystem (PROSE) device for enhanced targeted delivery of moxifloxiacin. Observations: A 62-year-old female presented with a 3-day history of pain, photophobia, and declining vision in left eye. The patient had a 2-year history of binocular PROSE treatment for ocular chronic graft-vs-host disease (cGVHD). A corneal ulcer was diagnosed and treated with topical 0.5\% moxifloxacin solution 6 times per day, with continued wear of the PROSE device. After 4 days, worsening symptoms led to an increase in application of moxifloxicin to every 2 hours while awake. The drug was administered by removal of the device, cleaning and replenishing the reservoir with sterile saline, and adding one drop of the drug to the reservoir prior to reinsertion. Four days later, the corneal surface was epithelialized with only small subepithelial infiltrate remaining. The corneal culture grew an isolate carrying multiple mutations in the topoisomerase genes. These mutations were correlated with varying levels of resistance to ciprofloxacin (256 μg/mL), levofloxacin (8 μg/mL), and moxifloxacin (16 μg/mL). Conclusions and Importance: Although the infecting strain exhibited resistance to fluoroquinolones, the infection resolved when moxifloxacin was combined with PROSE therapy. Frequent dosing to the PROSE reservoir is likely to increase fluoroquinolone bioavailability and may represent a valuable approach to overcome antibiotic resistance.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2018.09.006},
	author = {Zhai, Hualei and Bispo, Paulo J M and Kobashi, Hidenaga and Jacobs, Deborah S and Gilmore, Michael S and Ciolino, Joseph B}
}
@article {688681,
	title = {Multiple simultaneous choroidal melanomas arising in the same eye: globe salvage by radiotherapy.},
	journal = {Acta Ophthalmol},
	volume = {94},
	number = {8},
	year = {2016},
	month = {2016 Dec},
	pages = {e799-e802},
	abstract = {PURPOSE: Multiple choroidal melanomas arising in the same eye is a very rare entity, usually leading ophthalmologists to entertain other diagnoses. Historically, the only available treatment reported for this rare entity was enucleation. In this study we demonstrate in a series of patients with multiple simultaneous choroidal melanomas that eye salvage is possible using a variety of radiotherapy techniques. OBSERVATIONS: Both patients presented with two simultaneous choroidal melanomas in one eye. The first patient was only 30\&nbsp;years old and presented with two largely amelanotic tumours with large exudative retinal detachment. Cytology from fine needle aspiration biopsies from both tumours with immunohistochemistry confirmed two separate melanomas. Sequential radioactive iodine plaque brachytherapy led to regression of both tumours. The second, older patient{\textquoteright}s two tumours both had the typical appearance of choroidal melanoma and he underwent proton beam irradiation to the entire field leading to tumour regression. CONCLUSIONS: Multiple choroidal melanomas can rarely arise simultaneously in the same eye, and despite their variable appearance, a definitive diagnosis can be aided by cytology and immunohistochemistry in atypical-appearing cases. While all other previously reported cases have necessitated enucleation, we demonstrate that globe salvage is possible using either proton beam irradiation to the entire tumour field, or with sequential radioactive plaque brachytherapy.},
	issn = {1755-3768},
	doi = {10.1111/aos.13034},
	author = {Zhang, Matthew M and Papakostas, Thanos D and Malcolm, Arnold W and Ancell, Kristin K and Biscotti, Charles V and Gragoudas, Evangelos S and Daniels, Anthony B}
}
@article {1263441,
	title = {Comparative genomic analysis of two emergent human adenovirus type 14 respiratory pathogen isolates in China reveals similar yet divergent genomes},
	journal = {Emerg Microbes Infect},
	volume = {6},
	number = {11},
	year = {2017},
	month = {2017 Nov 01},
	pages = {e92},
	abstract = {Human adenovirus type 14 (HAdV-B14p) was originally identified as an acute respiratory disease (ARD) pathogen in The Netherlands in 1955. For approximately fifty years, few sporadic infections were observed. In 2005, HAdV-B14p1, a genomic variant, re-emerged and was associated with several large ARD outbreaks across the U.S. and, subsequently, in Canada, the U.K., Ireland, and China. This strain was associated with an unusually higher fatality rate than previously reported for both this prototype and other HAdV types in general. In China, HAdV-B14 was first observed in 2010, when two unrelated HAdV-B14-associated ARD cases were reported in Southern China (GZ01) and Northern China (BJ430), followed by three subsequent outbreaks. While comparative genomic analysis, including indel analysis, shows that the three China isolates, with whole genome data available, are similar to the de Wit prototype, all are divergent from the U.S. strain (303600; 2007). Although the genomes of strains GZ01 and BJ430 are nearly identical, as per their genome type characterization and percent identities, they are subtly divergent in their genome mutation patterns. These genomes indicate possibly two lineages of HAdV-B14 and independent introductions into China from abroad, or subsequent divergence from one; CHN2012 likely represents a separate sub-lineage. Observations of these simultaneously reported emergent strains in China add to the understanding of the circulation, epidemiology, and evolution of these HAdV pathogens, as well as provide a foundation for developing effective vaccines and public health strategies, including nationwide surveillance in anticipation of larger outbreaks with potentially higher fatality rates associated with HAdV-B14p1.},
	issn = {2222-1751},
	doi = {10.1038/emi.2017.78},
	author = {Zhang, Qiwei and Jing, Shuping and Cheng, Zetao and Yu, Zhiwu and Dehghan, Shoaleh and Shamsaddini, Amirhossein and Yan, Yuqian and Li, Min and Seto, Donald}
}
@article {1608605,
	title = {Demographic and prognostic factors of optic nerve astrocytoma: a retrospective study of surveillance, epidemiology, and end results (SEER)},
	journal = {BMC Cancer},
	volume = {21},
	number = {1},
	year = {2021},
	month = {2021 Aug 30},
	pages = {976},
	abstract = {BACKGROUND: Optic nerve astrocytomas (ONAs) are neurological neoplasms in the central nervous system (CNS), and they have the highest incidence rate among all the tumor types in the visual pathway. In this study, we conducted a Surveillance, Epidemiology, and End Results (SEER) -based research to explore the demographic, survival, and prognostic factors of patients diagnosed with ONAs. METHODS: Utilizing the SEER database, we retrospectively evaluated data of patients diagnosed with ONAs of all ages from 1984 to 2016. We used the Student{\textquoteright}s t distribution to test variables of patients and various characteristics, and Kaplan-Meier curve to illustrate overall survival (OS) with 95.0\% confidence intervals (CIs). We also performed univariate and multivariate analyses to evaluate various variables{\textquoteright} validity on overall survival. RESULTS: A total of 1004 cases were analyzed, and revealed that age (P\&lt;0.001, hazard ratio (HR) = 8.830, 95\% CI: 4.088-19.073), tumor grade (P\&lt;0.001, HR = 1.927, 95\% CI: 1.516-2.450), diagnostic confirmation (P\&lt;0.001, HR = 2.444, 95\% CI: 1.632-3.660), and histology type (P = 0.046, HR = 1.563, 95\% CI: 1.008-2.424) of the tumor were associated with decreased survival. CONCLUSIONS: From this large, comparative study of ONAs, we found that younger age may be considered as a protective indicator, while high-grade astrocytic tumors have a worse prognosis. We also found that diagnostic confirmation and tumor grade were independent prognostic factors in this patient population.},
	issn = {1471-2407},
	doi = {10.1186/s12885-021-08719-2},
	author = {Zhang, Mingui and Chen, Tao and Zhong, Yisheng}
}
@article {1661837,
	title = {Assessing visuospatial processing in cerebral visual impairment using a novel and naturalistic static visual search task},
	journal = {Res Dev Disabil},
	volume = {131},
	year = {2022},
	month = {2022 Dec},
	pages = {104364},
	abstract = {BACKGROUND: Cerebral visual impairment (CVI) is a brain based visual disorder associated with the maldevelopment of central visual pathways. Individuals with CVI often report difficulties finding a target of interest in cluttered and crowded visual scenes. However, it remains unknown how manipulating task demands and other environmental factors influence visual search performance in this population. AIM: We developed a novel and naturalistic virtual reality (VR) based static visual search task combined with eye tracking called the "virtual toy box" to objectively assess visual search performance in CVI. METHODS AND PROCEDURES: A total of 38 individuals with CVI (mean age 13.18 years\&nbsp;{\textpm}\&nbsp;3.58\&nbsp;SD) and 53 controls with neurotypical development (mean age 15.25 years\&nbsp;{\textpm}\&nbsp;5.72\&nbsp;SD) participated in the study. In a first experiment, study subjects were instructed to search for a preselected toy presented among a varying number of surrounding distractor toys (set size ranging from 1 to 36 items). In a second experiment, we assessed the effects of manipulating item spacing and the size of the visual area explored (field of view; FOV). OUTCOMES AND RESULTS: Behavioral outcomes collected were success rate, reaction time, gaze error, visual search area, and off-screen percent (an index of task compliance). Compared to age-matched controls, participants with CVI showed an overall impairment with respect to all the visual search outcomes of interest. Specifically, individuals with CVI were less likely and took longer to find the target, and search patterns were less accurate and precise compared to controls. Visual search response profiles were also comparatively less efficient and were associated with a slower initial pre-search (visual orienting) response as indexed by higher slope and intercept values derived from the analysis of reaction time\&nbsp;{\texttimes}\&nbsp;set size functions. Search performance was also more negatively affected in CVI at the smallest as well as largest spacing conditions tested, while increasing FOV was associated with greater decreased gaze accuracy and precision CONCLUSIONS AND IMPLICATIONS: These results are consistent with a general profile of impaired visual search abilities in CVI as well as worsening performance with increased visual task demands and an overall sensitivity to visual clutter and crowding. The observed profile of impaired visual search performance may be associated with dysfunctions related to how visual selective attention is deployed in individuals with CVI.},
	keywords = {Adolescent, Attention, Brain, Humans, Reaction Time, Vision Disorders},
	issn = {1873-3379},
	doi = {10.1016/j.ridd.2022.104364},
	author = {Zhang, Xin and Manley, Claire E and Micheletti, Serena and Tesic, Isidora and Bennett, Christopher R and Fazzi, Elisa M and Merabet, Lotfi B}
}
@article {1658674,
	title = {Uveitis Registries - A Digital Tool for Patient Care, Education, Research, and Collaboration},
	journal = {Ocul Immunol Inflamm},
	volume = {31},
	number = {9},
	year = {2023},
	month = {2023 Nov},
	pages = {1859-1869},
	abstract = {PURPOSE: Clinical registries are increasingly important in research and clinical advancement. This review explores and compares current uveitis registries and recommends future directions on how uveitis registries can complement one another for synergistic effect and benefit. METHODS: From a systematic search, 861 citations were screened for longitudinal, non-interventional, and multicenter uveitis-specific registries. Additional registries were identified via consultations with uveitis experts. Characteristics of all registries were analyzed and compared. RESULTS: Four registries were identified: Treatment Exit Options for Non-infectious Uveitis, AutoInflammatory Disease Alliance International Registry, Ocular Autoimmune Systemic Inflammatory Infectious Study, and Fight Uveitis Blindness!. Despite certain differences, these registries have the overarching goal of collecting large quantities of real-world, high-quality patient data to improve the understanding of uveitis. CONCLUSION: The four uveitis registries share similar goals and collect clinical data from overlapping geographical regions. There is vast potential for collaboration, including data sharing to further augment datasets for analysis.},
	keywords = {Eye, Eye Infections, Humans, Multicenter Studies as Topic, Patient Care, Registries, Uveitis},
	issn = {1744-5078},
	doi = {10.1080/09273948.2022.2140062},
	author = {Zhang, Zheting and Ng Ming Sheng, Sean and Kempen, John H and Fabiani, Claudia and Arora, Atul and Gupta, Vishali and Tsui, Edmund and Cimino, Luca and Symes, Richard J and Dell, Jennifer and Finger, Robert P and Heinz, Carsten and Agrawal, Rupesh}
}
@article {1302190,
	title = {Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium},
	journal = {Cell Host Microbe},
	volume = {23},
	number = {2},
	year = {2018},
	month = {2018 Feb 14},
	pages = {169-176.e6},
	abstract = {Botulinum neurotoxins (BoNTs), produced by various Clostridium strains, are a family of potent bacterial toxins and potential bioterrorism agents. Here we report that an Enterococcus faecium strain isolated from cow feces carries a BoNT-like toxin, designated BoNT/En. It cleaves both VAMP2 and SNAP-25, proteins that mediate synaptic vesicle exocytosis in neurons, at sites distinct from known BoNT\&nbsp;cleavage sites on these two proteins. Comparative genomic analysis determines that the E.\&nbsp;faecium strain carrying BoNT/En is a commensal type and that the BoNT/En gene is located within a typical BoNT gene cluster on a 206 kb putatively conjugative plasmid. Although the host species targeted by BoNT/En remains to be determined, these findings establish an extended member of BoNTs and demonstrate the capability of E.\&nbsp;faecium, a commensal organism ubiquitous in humans and animals and a leading cause of hospital-acquired multi-drug-resistant (MDR) infections, to horizontally acquire, and possibly disseminate, a unique BoNT gene cluster.},
	issn = {1934-6069},
	doi = {10.1016/j.chom.2017.12.018},
	author = {Zhang, Sicai and Lebreton, Francois and Mansfield, Michael J and Miyashita, Shin-Ichiro and Zhang, Jie and Schwartzman, Julia A and Tao, Liang and Masuyer, Geoffrey and Mart{\'\i}nez-Carranza, Markel and Stenmark, P{\r a}l and Gilmore, Michael S and Doxey, Andrew C and Dong, Min}
}
@article {1287966,
	title = {Superior oblique myokymia treated with levobunolol},
	journal = {J AAPOS},
	volume = {22},
	number = {1},
	year = {2018},
	month = {2018 Feb},
	pages = {67-69.e2},
	abstract = {Superior oblique myokymia (SOM) is an uncommon condition of unclear etiology that results in episodes of oscillopsia and diplopia. There is no established treatment protocol for SOM. We present 2 cases of SOM successfully managed with topical levobunolol 0.5\%; both patients responded to a short course of medication administration and required minimal ongoing therapy. Case 1 was a 69-year-old woman with left SOM who had previously undergone a left Harada-Ito procedure. Her SOM improved immediately on administration of levobunolol and was maintained at follow-up 1\&nbsp;year later. Case 2 was a 49-year-old man with right SOM that affected his ability to work. After 2\&nbsp;days of topical levobunolol 0.5\% nightly in the right eye, SOM episodes ceased; he continues to use drops intermittently for occasional recurrences.},
	issn = {1528-3933},
	doi = {10.1016/j.jaapos.2017.08.010},
	author = {Zhang, Mia and Gilbert, Aubrey L and Hunter, David G}
}
@article {1538316,
	title = {Exosomes mediate an epithelial-mesenchymal transition cascade in retinal pigment epithelial cells: Implications for proliferative vitreoretinopathy},
	journal = {J Cell Mol Med},
	year = {2020},
	month = {2020 Oct 13},
	abstract = {Exosomes have recently emerged as a pivotal mediator of many physiological and pathological processes. However, the role of exosomes in proliferative vitreoretinopathy (PVR) has not been reported. In this study, we aimed to investigate the role of exosomes in PVR. Transforming growth factor beta 2 (TGF{\ss}-2) was used to induce epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, as an in vitro model of PVR. Exosomes from normal and EMTed RPE cells were extracted and identified. We incubated extracted exosomes with recipient RPE cells, and co-cultured EMTed RPE cells and recipient RPE cells in the presence of the exosome inhibitor GW4869. Both experiments suggested that there are further EMT-promoting effects of exosomes from EMTed RPE cells. MicroRNA sequencing was also performed to identify the miRNA profiles in exosomes from both groups. We identified 34 differentially expressed exosomal miRNAs (P\&nbsp;\&lt;.\&nbsp;05). Importantly, miR-543 was found in exosomes from EMTed RPE cells, and miR-543-enriched exosomes significantly induced the EMT of recipient RPE cells. Our study demonstrates that exosomal miRNA is differentially expressed in RPE cells during EMT and that these exosomal miRNAs may play pivotal roles in EMT induction. Our results highlight the importance of exosomes as cellular communicators within the microenvironment of PVR.},
	issn = {1582-4934},
	doi = {10.1111/jcmm.15951},
	author = {Zhang, Yao and Wang, Kaizhe and Pan, Jiabin and Yang, Shuai and Yao, Haipei and Li, Min and Li, Hui and Lei, Hetian and Jin, Haiying and Wang, Fang}
}
@article {1806591,
	title = {Visual outcomes of children undergoing penetrating keratoplasty in the US},
	journal = {Ocul Surf},
	year = {2024},
	month = {2024 Feb 23},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2024.02.001},
	author = {Zhang, Lyvia J and Dana, Reza and Lorch, Alice C and Tobias Elze and Miller, Joan W and Dohlman, Thomas H and Oke, Isdin and IRIS{\textregistered} Registry Analytic Center Consortium}
}
@article {1233391,
	title = {Superior oblique myokymia},
	journal = {Surv Ophthalmol},
	year = {2017},
	month = {2017 Oct 19},
	abstract = {Superior oblique myokymia (SOM) is a rare condition of unclear etiology. We discuss the history, etiology, clinical features, differential diagnoses, management and prognosis of SOM. We conducted a meta-analysis of all 116 cases published since SOM was first described in 1906. The age at examination was 17-72 years (mean 42 years.) There was a right-sided preponderance in 61\% of cases (P \&lt; 0.02) that was statistically significant in females (63\%, P \&lt; 0.04) but not in males (59\%, P = 0.18). The pathophysiology of SOM may be neurovascular compression and/or ephaptic transmission. Although various pharmacological and surgical approaches to SOM treatment have been proposed, the rarity of the condition has made it impossible to conduct clinical trials evaluating the safety and efficacy of these approaches. Recently, topical beta-blockers have managed SOM symptoms in a number of cases, including the first case treated with levobunolol. Systemic medications, strabismus surgery, and neurosurgery have been used to control symptoms, with strabismus surgery carrying a moderate risk of post-operative diplopia in down-gaze. While there is no established treatment for SOM, we encourage clinicians to attempt topical levobunolol therapy before considering systemic therapy or surgery.},
	issn = {1879-3304},
	doi = {10.1016/j.survophthal.2017.10.005},
	author = {Zhang, Mia and Gilbert, Aubrey and Hunter, David}
}
@article {1364578,
	title = {Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish},
	journal = {Mol Biol Cell},
	volume = {23},
	number = {16},
	year = {2012},
	month = {2012 Aug},
	pages = {3069-78},
	abstract = {In our effort to understand genetic disorders of the photoreceptor cells of the retina, we have focused on intraflagellar transport in photoreceptor sensory cilia. From previous mouse proteomic data we identified a cilia protein Ttc26, orthologue of dyf-13 in Caenorhabditis elegans, as a target. We localized Ttc26 to the transition zone of photoreceptor and to the transition zone of cilia in cultured murine inner medullary collecting duct 3 (mIMCD3) renal cells. Knockdown of Ttc26 in mIMCD3 cells produced shortened and defective primary cilia, as revealed by immunofluorescence and scanning electron microscopy. To study Ttc26 function in sensory cilia in vivo, we utilized a zebrafish vertebrate model system. Morpholino knockdown of ttc26 in zebrafish embryos caused ciliary defects in the pronephric kidney at 27 h postfertilization and distension/dilation of pronephros at 5 d postfertilization (dpf). In the eyes, the outer segments of photoreceptor cells appeared shortened or absent, whereas cellular lamination appeared normal in retinas at 5 dpf. This suggests that loss of ttc26 function prevents normal ciliogenesis and differentiation in the photoreceptor cells, and that ttc26 is required for normal development and differentiation in retina and pronephros. Our studies support the importance of Ttc26 function in ciliogenesis and suggest that screening for TTC26 mutations in human ciliopathies is justified.},
	keywords = {Animals, Cell Line, Cilia, Gene Knockdown Techniques, Larva, Male, Mice, Morpholinos, Phenotype, Photoreceptor Cells, Pronephros, Protein Transport, Rats, RNA Interference, Zebrafish, Zebrafish Proteins},
	issn = {1939-4586},
	doi = {10.1091/mbc.E12-01-0019},
	author = {Zhang, Qi and Liu, Qin and Austin, Chrissy and Drummond, Iain and Pierce, Eric A}
}
@article {503991,
	title = {Knockdown of poc1b causes abnormal photoreceptor sensory cilium and vision impairment in zebrafish.},
	journal = {Biochem Biophys Res Commun},
	volume = {465},
	number = {4},
	year = {2015},
	month = {2015 Oct 2},
	pages = {651-7},
	abstract = {Proteomic analysis of the mouse photoreceptor sensory cilium identified a set of cilia proteins, including Poc1 centriolar protein b (Poc1b). Previous functional studies in human cells and zebrafish embryos implicated that Poc1b plays important roles in centriole duplication and length control, as well as ciliogenesis. To study the function of Poc1b in photoreceptor sensory cilia and other primary cilia, we expressed a tagged recombinant Poc1b protein in cultured renal epithelial cells and rat retina. Poc1b was localized to the centrioles and spindle bundles during cell cycle progression, and to the basal body of photoreceptor sensory cilia. A morpholino knockdown and complementation assay of poc1b in zebrafish showed that loss of poc1b led to a range of morphological anomalies of cilia commonly associated with human ciliopathies. In the retina, the development of retinal laminae was significantly delayed and the length of photoreceptor outer segments was shortened. Visual behavior studies revealed impaired visual function in the poc1b morphants. In addition, ciliopathy-associated developmental defects, such as small eyes, curved body axis, heart defects, and shortened cilia in Kupffer{\textquoteright}s vesicle, were observed as well. These data suggest that poc1b is required for normal development and ciliogenesis of retinal photoreceptor sensory cilia and other cilia. Furthermore, this conclusion is supported by recent findings that mutations in POC1B gene have been identified in patients with inherited retinal dystrophy and syndromic retinal ciliopathy.},
	issn = {1090-2104},
	doi = {10.1016/j.bbrc.2015.06.083},
	author = {Zhang, Conghui and Zhang, Qi and Wang, Fang and Liu, Qin}
}
@article {1580470,
	title = {Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis},
	journal = {Eur J Hum Genet},
	volume = {29},
	number = {6},
	year = {2021},
	month = {2021 Jun},
	pages = {998-1007},
	abstract = {WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G \&gt; A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein{\textquoteright}s putative involvement in multiple developmental and stem cell maintenance pathways.},
	issn = {1476-5438},
	doi = {10.1038/s41431-021-00812-1},
	author = {Zhang, Yanjia Jason and Jimenez, Lissette and Azova, Svetlana and Kremen, Jessica and Chan, Yee-Ming and Elhusseiny, Abdelrahman M and Saeed, Hajirah and Goldsmith, Jeffrey and Al-Ibraheemi, Alyaa and O{\textquoteright}Connell, Amy E and Kovbasnjuk, Olga and Rodan, Lance and Agrawal, Pankaj B and Thiagarajah, Jay R}
}
@article {1651375,
	title = {AOSLO-net: A Deep Learning-Based Method for Automatic Segmentation of Retinal Microaneurysms From Adaptive Optics Scanning Laser Ophthalmoscopy Images},
	year = {2022},
	author = {Zhang, Q and Sampani, K and Xu, M. and Cai, S and Deng, Y and H. Li and Sun, J K and Karniadakis, GE}
}
@article {669341,
	title = {Comparison of Early Changes in Ocular Surface and Inflammatory Mediators between Femtosecond Lenticule Extraction and Small-Incision Lenticule Extraction.},
	journal = {PLoS One},
	volume = {11},
	number = {3},
	year = {2016},
	month = {2016},
	pages = {e0149503},
	abstract = {PURPOSE: To evaluate the short-term changes in ocular surface measures and tear inflammatory mediators after femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) procedures. METHODS: Eighteen subjects (18 eyes) underwent FLEx and 23 subjects (23 eyes) underwent SMILE in this single-center and prospective study. Central corneal sensitivity, Schirmer I test (SIT), noninvasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein (FL) staining, and ocular surface disease index (OSDI) were assessed in all patients. Concentrations of interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) in collected tears were measured by multiplex antibody microarray. RESULTS: Central corneal sensitivity was reduced in both groups, but the scores in the SMILE group were higher than those in the FLEx group at all time points postoperatively (P\&lt;0.01). Lower FL scores and longer NI-BUT were observed in the SMILE group 1 week after surgery (P\&lt;0.05). OSDI scores in both groups increased rapidly at 1 day and 1 week postoperatively, then returned to their preoperative levels within 1 month (P\&lt;0.05). There were no significant differences in SIT or tear meniscus height between the two groups. Lower and faster recovery of tear NGF, TGF-β1 and IL-1α concentration were found in the SMILE group compared to the FLEx group postoperatively. No significant difference was found in tear TNF-α, IFN-γ and MMP-9 for either group before or after surgery. Tear NGF, TGF-β1 and IL-1α show a correlation with ocular surface changes after FLEx or SMILE surgery. CONCLUSION: SMILE has superiority over FLEx in early ocular surface changes and NGF, TGF-β1 and IL-1α may contribute to the process of ocular surface recovery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02540785.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0149503},
	author = {Zhang, Chi and Ding, Hui and He, Miao and Liu, Lina and Liu, Liangping and Li, Gang and Niu, Bing and Zhong, Xingwu}
}
@article {1109906,
	title = {Influence of Pilocarpine and Timolol on Human Meibomian Gland Epithelial Cells},
	journal = {Cornea},
	volume = {36},
	number = {6},
	year = {2017},
	month = {2017 Jun},
	pages = {719-724},
	abstract = {PURPOSE: Investigators have discovered that topical antiglaucoma drugs may induce meibomian gland dysfunction. This response may contribute to the dry eye disease commonly found in patients with glaucoma taking such medications. We hypothesize that drug action involves a direct effect on human meibomian gland epithelial cells (HMGECs). To test this hypothesis, we examined the influence of the antiglaucoma drugs, pilocarpine and timolol, on the morphology, survival, proliferation, and differentiation of HMGECs. METHODS: Immortalized (I) HMGECs (n = 2-3 wells/treatment/experiment) were cultured with multiple concentrations of pilocarpine or timolol for up to 7 days. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract) and differentiation (azithromycin). Cells were enumerated using a hemocytometer and evaluated for morphology, neutral lipid staining, and lysosome accumulation. RESULTS: Our results demonstrate that pilocarpine and timolol cause a dose-dependent decrease in the survival of IHMGECs. The clinically used concentrations are toxic and lead to cell atrophy, poor adherence, or death. By contrast, drug levels that are known to accumulate within the conjunctiva, adjacent to the meibomian glands, do not influence IHMGEC survival. These latter concentrations also have no effect on IHMGEC proliferation or differentiation, and they do not interfere with the ability of azithromycin to stimulate cellular neutral lipid and lysosome accumulation. This dose of pilocarpine, though, did suppress the epidermal growth factor+bovine pituitary extract-induced proliferation of IHMGECs. CONCLUSIONS: Our results support our hypothesis and demonstrate that these antiglaucoma drugs, pilocarpine and timolol, have direct effects on HMGECs that may influence their morphology, survival, and proliferative capacity.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000001181},
	author = {Zhang, Yi and Kam, Wendy R and Liu, Yang and Chen, Xiaomin and Sullivan, David A}
}
@article {1789191,
	title = {Generation of a human induced pluripotent stem cell line (OGIi001) from peripheral blood mononuclear cells of a healthy male donor},
	journal = {Stem Cell Res},
	volume = {74},
	year = {2024},
	month = {2024 Feb},
	pages = {103280},
	abstract = {We have successfully derived a novel human induced pluripotent stem cell (hiPSC) line using non-integrative Sendai virus. This hiPSC line was generated from a healthy male adult donor, aged 55, and subjected to thorough characterization and extensive quality control. The analysis confirmed the expression of undifferentiated stem cell markers, demonstrated the ability to differentiate into the three germ layers, and revealed the absence of any chromosomal abnormalities.},
	keywords = {Adult, Cell Differentiation, Cell Line, Cellular Reprogramming, Chromosome Aberrations, Humans, Induced Pluripotent Stem Cells, Leukocytes, Mononuclear, Male, Sendai virus},
	issn = {1876-7753},
	doi = {10.1016/j.scr.2023.103280},
	author = {Zhang, Hanmeng and Daheron, Laurence and Cerna-Chavez, Rodrigo and Place, Emily M and Huckfeldt, Rachel M and Pierce, Eric A and Garita-Hernandez, Marcela}
}
@article {913566,
	title = {A novel, multiplexed targeted mass spectrometry assay for quantification of complement factor H (CFH) variants and CFH-related proteins 1-5 in human plasma},
	journal = {Proteomics},
	volume = {17},
	number = {6},
	year = {2017},
	month = {2017 Mar},
	abstract = {Age-related macular degeneration (AMD) is a leading cause of visual loss among older adults. Two variants in the complement factor H (CFH) gene, Y402H and I62V, are strongly associated with risk of AMD. CFH is encoded in regulator of complement activation gene cluster in chromosome 1q32, which includes complement factor related (CFHR) proteins, CFHR1 to CFHR5, with high amino acid sequence homology to CFH. Our goal was to build a SRM assay to measure plasma concentrations of CFH variants Y402, H402, I62, and V62, and CFHR1-5. The final assay consisted of 24 peptides and 72 interference-free SRM transition ion pairs. Most peptides showed good linearity over 0.3-200 fmol/μL concentration range. Plasma concentrations of CFH variants and CFHR1-5 were measured using the SRM assay in 344 adults. Plasma CFH concentrations (mean, SE in μg/mL) by inferred genotype were: YY402, II62 (170.1, 31.4), YY402, VV62 (188.8, 38.5), HH402, VV62 (144.0, 37.0), HY402, VV62 (164.2, 42.3), YY402, IV62 (194.8, 36.8), HY402, IV62 (181.3, 44.7). Mean (SE) plasma concentrations of CFHR1-5 were 1.63 (0.04), 3.64 (1.20), 0.020 (0.001), 2.42 (0.18), and 5.49 (1.55) μg/mL, respectively. This SRM assay should facilitate the study of the role of systemic complement and risk of AMD.},
	issn = {1615-9861},
	doi = {10.1002/pmic.201600237},
	author = {Zhang, Pingbo and Zhu, Min and Geng-Spyropoulos, Minghui and Shardell, Michelle and Gonzalez-Freire, Marta and Gudnason, Vilmundur and Eiriksdottir, Gudny and Schaumberg, Debra and Van Eyk, Jennifer E and Ferrucci, Luigi and Semba, Richard D}
}
@article {1789096,
	title = {Temporal keratoconus in a pediatric patient},
	journal = {Am J Ophthalmol Case Rep},
	volume = {32},
	year = {2023},
	month = {2023 Dec},
	pages = {101900},
	abstract = {PURPOSE: To report a pediatric patient with bilateral temporal keratoconus. OBSERVATIONS: A 14-year-old male presented with a two-year history of progressively worsening visual acuity in both eyes and suspicion for undiagnosed amblyopia in the right eye. Retinoscopy revealed a scissoring reflex in both eyes and corneal topography demonstrated high keratometry values (Kmax 57.9 D and 46.1 D in the right and left eyes, respectively), with relative temporal steepening approximately coinciding with the thinnest pachymetry in both eyes. Corneal cross-linking was recommended. CONCLUSIONS AND IMPORTANCE: Keratoconus can present as a temporal variant with relative temporal steepening and thinning. It is important to maintain a high index of suspicion for keratoconus in pediatric patients with sub-normal visual acuities. Prompt assessment and diagnosis may prevent progression of keratoconus and development of amblyopia.},
	issn = {2451-9936},
	doi = {10.1016/j.ajoc.2023.101900},
	author = {Zhang, Lyvia J and Traish, Aisha S and Dohlman, Thomas H}
}
@article {1635634,
	title = {AMD Genomics: Non-Coding RNAs as Biomarkers and Therapeutic Targets},
	journal = {J Clin Med},
	volume = {11},
	number = {6},
	year = {2022},
	month = {2022 Mar 09},
	abstract = {Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that is the world{\textquoteright}s leading cause of blindness in the aging population. Although the clinical stages and forms of AMD have been elucidated, more specific prognostic tools are required to determine when patients with early and intermediate AMD will progress into the advanced stages of AMD. Another challenge in the field has been the appropriate development of therapies for intermediate AMD and advanced atrophic AMD. After numerous negative clinical trials, an anti-C5 agent and anti-C3 agent have recently shown promising results in phase 3 clinical trials, in terms of slowing the growth of geographic atrophy, an advanced form of AMD. Interestingly, both drugs appear to be associated with an increased incidence of wet AMD, another advanced form of the disease, and will require frequent intravitreal injections. Certainly, there remains a need for other therapeutic agents with the potential to prevent progression to advanced stages of the disease. Investigation of the role and clinical utility of non-coding RNAs (ncRNAs) is a major advancement in biology that has only been minimally applied to AMD. In the following review, we discuss the clinical relevance of ncRNAs in AMD as both biomarkers and therapeutic targets.},
	issn = {2077-0383},
	doi = {10.3390/jcm11061484},
	author = {Zhang, Charles and Owen, Leah A and Lillvis, John H and Zhang, Sarah X and Kim, Ivana K and Deangelis, Margaret M}
}
@article {1761871,
	title = {Psychosocial Well-Being and Quality of Life in Uveitis: A Review},
	journal = {Ocul Immunol Inflamm},
	year = {2023},
	month = {2023 Sep 15},
	pages = {1-15},
	abstract = {PURPOSE: As a potentially sight-threatening disease with ocular, systemic, and treatment-related complications, uveitis diminishes quality of life (QOL) and affects psychosocial well-being. This review summarizes the existing tools for evaluating psychosocial well-being and/or QOL in patients with uveitis, explores the biological and non-biological factors affecting psychosocial well-being and/or QOL, and proposes future directions for incorporating these tools into clinical practice. METHODS: A systematic search of the MEDLINE, Embase, and Cochrane databases from inception to June 8, 2022 was conducted, screening for articles focused on psychosocial well-being and/or QOL in patients with uveitis. Both quantitative and qualitative analyses were performed. RESULTS: In uveitis research, the most frequently studied patient-reported outcome measures were vision-related QOL (e.g. Visual Function Questionnaire [VFQ-25]) and health-related QOL (e.g. Short Form Survey [SF-36]), followed by mental health indicators including depression and anxiety. Instruments have also been developed specific to the pediatric population (e.g. Effects of Youngsters{\textquoteright} Eyesight on Quality of Life [EYE-Q]). Generally, studies report worse psychosocial outcomes and QOL in patients with uveitis compared to the general population. Contributory factors include both clinical (e.g. visual impairment, ocular comorbidities) and patient-related (e.g. older age, female sex) factors. CONCLUSION: Given the heterogeneity of instruments used, it is worth considering standardization across large uveitis studies and trials. Beyond research, given the biopsychosocial effects on patients with uveitis, there are benefits to incorporating QOL and psychosocial assessments into clinical practice. Simplification of questionnaires into abridged forms, focusing on the most clinically relevant aspects of patient care, may be considered.},
	issn = {1744-5078},
	doi = {10.1080/09273948.2023.2247077},
	author = {Zhang, Zheting and Griva, Konstadina and Rojas-Carabali, William and Patnaik, Gazal and Liu, Renee and Sobrin, Lucia and Kempen, John H and Finger, Robert P and Gupta, Vishali and Ang, Bryan and Agrawal, Rupesh}
}
@article {1424821,
	title = {Diagnostic Utility of Optic Nerve Measurements with MRI in Patients with Optic Nerve Atrophy},
	journal = {AJNR Am J Neuroradiol},
	volume = {40},
	number = {3},
	year = {2019},
	month = {2019 Mar},
	pages = {558-561},
	abstract = {BACKGROUND AND PURPOSE: No MR imaging measurement criteria are available for the diagnosis of optic nerve atrophy. We determined a threshold optic nerve area on MR imaging that predicts a clinical diagnosis of optic nerve atrophy and assessed the relationship between optic nerve area and retinal nerve fiber layer thickness measured by optical coherence tomography, an ancillary test used to evaluate optic nerve disorders. MATERIALS AND METHODS: We evaluated 26 patients with suspected optic nerve atrophy (8 with unilateral, 13 with bilateral and 5 with suspected but not demonstrable optic nerve atrophy) who had both orbital MR imaging and optical coherence tomography examinations. Forty-five patients without optic nerve atrophy served as controls. Coronal inversion recovery images were used to measure optic nerve area on MR imaging. Retinal nerve fiber layer thickness was determined by optical coherence tomography. Individual eyes were treated separately; however, bootstrapping was used to account for clustering when appropriate. Correlation coefficients were used to evaluate relationships; receiver operating characteristic curves, to investigate predictive accuracy. RESULTS: There was a significant difference in optic nerve area between patients{\textquoteright} affected eyes with optic nerve atrophy (mean, 3.09 {\textpm} 1.09 mm), patients{\textquoteright} unaffected eyes (mean, 5.27 {\textpm} 1.39 mm; = .008), and control eyes (mean, 6.27 {\textpm} 2.64 mm; \&lt; .001). Optic nerve area <= 4.0 mm had a sensitivity of 0.85 and a specificity of 0.83 in predicting the diagnosis of optic nerve atrophy. A significant relationship was found between optic nerve area and retinal nerve fiber layer thickness ( = 0.68, \&lt; .001). CONCLUSIONS: MR imaging-measured optic nerve area <= 4.0 mm has moderately high sensitivity and specificity for predicting optic nerve atrophy, making it a potential diagnostic tool for radiologists.},
	issn = {1936-959X},
	doi = {10.3174/ajnr.A5975},
	author = {Zhao, B. and Torun, N and Elsayed, M and Cheng, A-D and Brook, A and Chang, Y-M and Bhadelia, R A}
}
@article {1748541,
	title = {Refractive Accuracy and Visual Outcome by Self-Refraction Using Adjustable-Focus Spectacles in Young Children: A Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	year = {2023},
	month = {2023 Aug 24},
	abstract = {IMPORTANCE: Uncorrected refractive error is the most common cause of vision impairment in children. Most children 12 years or older can achieve visual acuity (VA) of 20/25 or better by self-refraction using adjustable-focus spectacles, but data on younger children are lacking. OBJECTIVE: To assess refractive accuracy, corrected VA, and factors associated with not achieving VA of 20/25 or better among children aged 5 to 11 years performing self-refraction with Adspecs adjustable-focus spectacles (Adaptive Eyecare), compared with noncycloplegic autorefraction and cycloplegic refraction. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional noninferiority trial conducted from September 2, 2015, to December 14, 2017. The study setting was an academic pediatric eye clinic. Children aged 5 to 11 years with uncorrected VA of 20/40 or worse in 1 or both eyes and without systemic or ocular conditions preventing best-corrected VA of 20/25 or better were enrolled. Children who had best-corrected VA worse than 20/25 were excluded. Study data were analyzed from September 2017 to June 2023. EXPOSURES: Children were taught to self-refract with adjustable-focus spectacles. MAIN OUTCOMES AND MEASURES: Spherical equivalent refractive error (using self-refraction, noncycloplegic autorefraction, and cycloplegic refraction) and VA (uncorrected and using self-refraction, noncycloplegic autorefraction, and cycloplegic refraction) for study eyes were evaluated. Potential predictors of failure to achieve VA of 20/25 or better with self-refraction were assessed using logistic regression. RESULTS: A total of 127 consecutive children were enrolled. After exclusions, 112 children (median [IQR] age, 9.0 [8.0-10.3] years; 52 boys [46.4\%]) were included in the study. Mean (SD) spherical equivalent refractive power was -2.00 (1.52) diopters (D) for self-refraction, -2.32 (1.43) D for noncycloplegic autorefraction, and -1.67 (1.49) D for cycloplegic refraction. Mean (SD) difference in refractive power between self-refraction and noncycloplegic autorefraction was 0.32 (1.11) D (97.5\% 1-sided CI, 0.11 to $\infty$ D; P \&lt; .001) and between self-refraction and cycloplegic refraction was -0.33 (1.15) D (97.5\% 1-sided CI, -0.54 to $\infty$ D; P = .77). The proportion of children with corrected VA of 20/25 or better was 79.5\% (89 of 112) with self-refraction, 85.7\% (96 of 112) with noncycloplegic autorefraction, and 79.5\% (89 of 112) with cycloplegic refraction (self-refraction vs noncycloplegic autorefraction: McNemar P value = .27; self-refraction vs cycloplegic refraction: McNemar P value \&gt; .99). Those failing to achieve best-corrected VA of 20/25 or better with self-refraction had higher astigmatism (odds ratio [OR], 10.6; 95\% CI, 3.1-36.4; P \&lt; .001) and younger age (OR, 1.5; 95\% CI, 1.1-2.2; P = .02). CONCLUSIONS AND RELEVANCE: Self-refraction among children aged 5 to 11 years may result in more myopic power than cycloplegic refraction but not necessarily to a clinically relevant degree. Although the proportion of children achieving VA of 20/25 or better with self-refraction using adjustable-focus spectacles did not differ from cycloplegic refraction, it was less likely among younger children and those with higher astigmatism.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2023.3508},
	author = {Zhao, Lloyd and Wen, Qing and Nasrazadani, David and Cheung, Nathan L and Weinert, Marguerite C and Freedman, Sharon F and Silver, Joshua and Priestley, Yos M and Congdon, Nathan and Prakalapakorn, S Grace}
}
@article {1059861,
	title = {Serum Th1 and Th17 related cytokines and autoantibodies in patients with Posner-Schlossman syndrome},
	journal = {PLoS One},
	volume = {12},
	number = {4},
	year = {2017},
	month = {2017},
	pages = {e0175519},
	abstract = {Posner-Schlossman syndrome (PSS) shares some clinical features with uveitis and open angle glaucoma. Cytokines and autoantibodies have been associated with uveitis and open angle glaucoma. However, the role of serum cytokines and autoantibodies in the pathogenesis of PSS remains unknown. This study aimed to evaluate the associations of type 1 T helper (Th1) and Th17 related cytokines and autoantibodies with PSS. Peripheral blood serum samples were collected from 81 patients with PSS and 97 gender- and age-matched healthy blood donors. Th1 and Th17 related cytokines, including interleukin-1β (IL-1β), IL-12, tumor necrosis factor-α (TNF-α), interferon- γ (IFN-γ), IL-6 and IL-17, and glucose-6-phosphate isomerase (GPI) were determined by double antibody sandwich ELISA. Anti-nuclear antibody (ANA), anti-keratin antibody (AKA) and anti-neutrophil cytoplasmic antibody (ANCA) were detected by indirect immunofluorescence assay. Anti-cardiolipin antibody (ACA)-IgG, ACA-IgM, ACA-IgA, anti-double stranded DNA (anti-dsDNA) and anti-cyclic citrullinated peptide antibody (anti-CCP) were detected by indirect ELISA. Serum levels of IL-1β, IL-12 and IL-6 in PSS patients were significantly lower than those in controls (P \&lt; 0.003), and these associations survived the Bonferroni correction (Pc \&lt; 0.018). There was no significant difference in serum levels of TNF-α, IFN-γ and IL-17 between the PSS and control groups (Pc \&gt; 0.12). Positive rate of serum anti-dsDNA in PSS patients was significantly higher than that in the control group (P = 0.002, Pc = 0.018), while positive rates of serum ANA, AKA, ANCA, ACA-IgG, ACA-IgM, ACA-IgA, GPI and anti-CCP in the PSS group were not significantly different from those in the control group (Pc \&gt; 0.09). These results suggest that anti-dsDNA may contribute to the pathogenesis of PSS, while Th1 and Th17 related cytokines and other autoantibodies may not be major contributors to PSS.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0175519},
	author = {Zhao, Jun and Chen, Wenchieh and Huang, Xiaosheng and Peng, Shiming and Zhu, Tianhui and Deng, Zhihui and Liang, Ping and Chang, Hui and Fan, Bao Jian}
}
@article {961741,
	title = {Optic neuropathy and increased retinal glial fibrillary acidic protein due to microbead-induced ocular hypertension in the rabbit.},
	journal = {Int J Ophthalmol},
	volume = {9},
	number = {12},
	year = {2016},
	month = {2016},
	pages = {1732-1739},
	abstract = {AIM: To characterize whether a glaucoma model with chronic elevation of the intraocular pressure (IOP) was able to be induced by anterior chamber injection of microbeads in rabbits. METHODS: In order to screen the optimal dose of microbead injection, IOP was measured every 3d for 4wk using handheld applanation tonometer after a single intracameral injection of 10 {\textmu}L, 25 {\textmu}L, 50 {\textmu}L or 100 {\textmu}L microbeads (5{\texttimes}10(6) beads/mL; n=6/group) in New Zealand White rabbits. To prolong IOP elevation, two intracameral injections of 50 {\textmu}L microbeads or phosphate buffer saline (PBS) were made respectively at days 0 and 21 (n=24/group). The fellow eye was not treated. At 5wk after the second injection of microbeads or PBS, bright-field microscopy and transmission electron microscopy (TEM) were used to assess the changes in the retina. The expression of glial fibrillary acidic protein (GFAP) in the retina was evaluated by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot at 5wk after the second injection of microbeads. RESULTS: Following a single intracameral injection of 10 {\textmu}L, 25 {\textmu}L, 50 {\textmu}L or 100 {\textmu}L microbead, IOP levels showed a gradual increase and a later decrease over a 4wk period after a single injection of microbead into the anterior chamber of rabbits. A peak IOP was observed at day 15 after injection. No significant difference in peak value of IOP was found between 10 {\textmu}L and 25 {\textmu}L groups (17.13{\textpm}1.25 mm Hg vs 17.63{\textpm}0.74 mm Hg; P=0.346). The peak value of IOP from 50 {\textmu}L group (23.25{\textpm}1.16 mm Hg) was significantly higher than 10 {\textmu}L and 25 {\textmu}L groups (all P\&lt;0.05). Administration of 100 {\textmu}L microbead solution (23.00{\textpm}0.93 mm Hg) did not lead to a significant increase in IOP compared to the 50 {\textmu}L group (P=0.64). A prolonged elevated IOP duration up to 8wk was achieved by administering two injections of 50 {\textmu}L microbeads (20.48{\textpm}1.21 mm Hg vs 13.60{\textpm}0.90 mm Hg in PBS-injected group; P\&lt;0.05). The bright-field and TEM were used to assess the changes of retinal ganglion cells (RGCs). Compared with PBS-injected group, the extended IOP elevation was associated with the degeneration of optic nerve, the reduction of RGC axons (47.16\%, P\&lt;0.05) and the increased GFAP expression in the retina (4.74{\textpm}1.10 vs 1.00{\textpm}0.46, P\&lt;0.05). CONCLUSION: Two injections of microbeads into the ocular anterior chamber of rabbits lead to a prolonged IOP elevation which results in structural abnormality as well as loss in RGCs and their axons without observable ocular structural damage or inflammatory response. We have therefore established a novel and practical model of experimental glaucoma in rabbits.},
	issn = {2222-3959},
	doi = {10.18240/ijo.2016.12.05},
	author = {Zhao, Jun and Zhu, Tian-Hui and Chen, Wen-Chieh and Peng, Shi-Ming and Huang, Xiao-Sheng and Cho, Kin-Sang and Chen, Dong Feng and Liu, Guei-Sheung}
}
@article {504036,
	title = {Human Leukocyte Antigens-B and -C Loci Associated with Posner-Schlossman Syndrome in a Southern Chinese Population.},
	journal = {PLoS One},
	volume = {10},
	number = {7},
	year = {2015},
	month = {2015},
	pages = {e0132179},
	abstract = {The etiology of Posner-Schlossman syndrome (PSS) remains unknown. The association of human leukocyte antigens (HLA) allelic diversity with PSS has been poorly investigated. To evaluate the association of allelic polymorphisms of class I HLA-A, -B and -C and class II HLA-DRB1 and -DQB1 with PSS, 100 unrelated patients with PSS and 128 age- and ethnically matched control subjects were recruited from a southern Chinese Han population. Polymorphisms in exons 2-4 for HLA-A, -B, -C loci, exon 2 for HLA-DRB1 and exons 2,3 for HLA-DQB1 were analyzed for association with PSS at allele and haplotype levels. The allele frequency of HLA-C*1402 in PSS patients was significantly higher than that in controls (P = 0.002, OR = 4.12). This association survived the Bonferroni correction (Pc = 0.04). The allele frequency of HLA-B*1301 in PSS patients was lower than that in the control group (P = 0.003, OR = 0.21), although this association did not survive the Bonferroni correction (Pc = 0.16). In PSS patients, the haplotype frequencies of HLA-A*1101~C*1402 and B*5101~C*1402 were higher than that in controls (P = 0.03, OR = 4.44; P = 0.02, OR = 3.20; respectively), while the HLA-B*1301~C*0304 was lower than that in controls (P = 0.007, OR = 0.23), although these associations did not survive the Bonferroni correction (Pc \&gt; 0.16). This study for the first time demonstrated that polymorphisms at the HLA-B and HLA-C loci were nominally associated with PSS in the southern Chinese Han population. Our results suggest that HLA-C*1402, A*1101~C*1402 and B*5101~C*1402 might be risk factors for PSS, whereas HLA-B*1301 plus B*1301~C*0304 might be protective factors against PSS, but even larger datasets are required to confirm these findings. Findings from this study provide valuable new clues for investigating the mechanisms and development of new diagnosis and treatment for PSS.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0132179},
	author = {Zhao, Jun and Zhu, Tianhui and Chen, Wenjie and Fan, Bao Jian and He, Liumei and Yang, Baocheng and Deng, Zhihui}
}
@article {1635638,
	title = {Neurons detect cognitive boundaries to structure episodic memories in humans},
	journal = {Nat Neurosci},
	volume = {25},
	number = {3},
	year = {2022},
	month = {2022 Mar},
	pages = {358-368},
	abstract = {While experience is continuous, memories are organized as discrete events. Cognitive boundaries are thought to segment experience and structure memory, but how this process is implemented remains unclear. We recorded the activity of single neurons in the human medial temporal lobe (MTL) during the formation and retrieval of memories with complex narratives. Here, we show that neurons responded to abstract cognitive boundaries between different episodes. Boundary-induced neural state changes during encoding predicted subsequent recognition accuracy but impaired event order memory, mirroring a fundamental behavioral tradeoff between content and time memory. Furthermore, the neural state following boundaries was reinstated during both successful retrieval and false memories. These findings reveal a neuronal substrate for detecting cognitive boundaries that transform experience into mnemonic episodes and structure mental time travel during retrieval.},
	issn = {1546-1726},
	doi = {10.1038/s41593-022-01020-w},
	author = {Zheng, Jie and Schjetnan, Andrea G P and Yebra, Mar and Gomes, Bernard A and Mosher, Clayton P and Kalia, Suneil K and Valiante, Taufik A and Mamelak, Adam N and Kreiman, Gabriel and Rutishauser, Ueli}
}
@article {1528400,
	title = {HIT-COVID, a global database tracking public health interventions to COVID-19},
	journal = {Sci Data},
	volume = {7},
	number = {1},
	year = {2020},
	month = {2020 Aug 27},
	pages = {286},
	abstract = {The COVID-19 pandemic has sparked unprecedented public health and social measures (PHSM) by national and local governments, including border restrictions, school closures, mandatory facemask use and stay at home orders. Quantifying the effectiveness of these interventions in reducing disease transmission is key to rational policy making in response to the current and future pandemics. In order to estimate the effectiveness of these interventions, detailed descriptions of their timelines, scale and scope are needed. The Health Intervention Tracking for COVID-19 (HIT-COVID) is a curated and standardized global database that catalogues the implementation and relaxation of COVID-19 related PHSM. With a team of over 200 volunteer contributors, we assembled policy timelines for a range of key PHSM aimed at reducing COVID-19 risk for the national and first administrative levels (e.g. provinces and states) globally, including details such as the degree of implementation and targeted populations. We continue to maintain and adapt this database to the changing COVID-19 landscape so it can serve as a resource for researchers and policymakers alike.},
	issn = {2052-4463},
	doi = {10.1038/s41597-020-00610-2},
	author = {Zheng, Qulu and Jones, Forrest K and Leavitt, Sarah V and Ung, Lawson and Labrique, Alain B and Peters, David H and Lee, Elizabeth C and Azman, Andrew S and HIT-COVID Collaboration}
}
@article {1580486,
	title = {Fatty acid oxidation and photoreceptor metabolic needs},
	journal = {J Lipid Res},
	year = {2021},
	month = {2021 Feb 05},
	pages = {100035},
	issn = {1539-7262},
	doi = {10.1194/jlr.TR120000618},
	author = {Zhongjie, Fu and Kern, Timothy S and Ann, Hellstr{\"o}m and Smith Lois, E H}
}
@article {1109911,
	title = {A Compact Whole-Eye Perfusion System to Evaluate Pharmacologic Responses of Outflow Facility},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {7},
	year = {2017},
	month = {2017 Jun 01},
	pages = {2991-3003},
	abstract = {Purpose: To discover novel therapies that lower IOP by increasing aqueous humor outflow facility, ex vivo ocular perfusion systems provide a valuable tool. However, currently available designs are limited by their throughput. Here we report the development of a compact, scalable perfusion system with improved throughput and its validation using bovine and porcine eyes. Methods: At a fixed IOP of 6 mm Hg, flow rate was measured by flow sensors. We validated the system by measuring the outflow responses to Y-39983 (a Rho kinase inhibitor), endothelin-1 (ET-1), ambrisentan (an antagonist for endothelin receptor A [ETA]), sphigosine-1-phosphate (S1P), JTE-013 (antagonist for S1P receptor 2 [S1P2]), S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide [NO] donor), and 3-Morpholino-sydnonimine (SIN-1, another NO donor). Results: The instrument design enabled simultaneous measurements of 20 eyes with a footprint of 1 m2. Relative to vehicle control, Y-39983 increased outflow by up to 31\% in calf eyes. On the contrary, ET-1 decreased outflow by up to 79\%, a response that could be blocked by pretreatment with ambrisentan, indicating a role for ETA receptors. Interestingly, the effect of ET-1 was also inhibited by up to 70\% to 80\% by pretreatment with NO donors, SNAP and SIN-1. In addition to testing in calf eyes, similar effects of ET-1 and ambrisentan were observed in adult bovine and porcine eyes. Conclusions: The compact eye perfusion platform provides an opportunity to efficiently identify compounds that influence outflow facility and may lead to the discovery of new glaucoma therapies.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20974},
	author = {Zhou, Enhua H. and Paolucci, Michael and Dryja, Thaddeus P and Manley, Ted and Xiang, Chuanxi and Rice, Dennis S and Prasanna, Ganesh and Chen, Amy}
}
@article {913571,
	title = {Role of MyD88 in adenovirus keratitis.},
	journal = {Immunol Cell Biol},
	volume = {95},
	number = {1},
	year = {2017},
	pages = {108-116},
	abstract = {Pattern recognition receptors (PRRs) are critical to the early detection and innate immune responses to pathogens. In particular, the toll-like receptor (TLR) system and its associated adaptor proteins have essential roles in early host responses to infection. Epidemic keratoconjunctivitis, caused by the human adenovirus, is a severe ocular surface infection associated with corneal inflammation (stromal keratitis). We previously showed that adenovirus capsid was a key molecular pattern in adenovirus keratitis, with viral DNA having a lesser role. We have now investigated the role of the adaptor molecule MyD88 in a mouse model of adenovirus keratitis in which there is no viral replication. In MyD88(-/-) mice infected with human adenovirus type 37, clinical keratitis was markedly reduced, along with infiltration of CD45(+) cells, and expression of inflammatory cytokines. Reduction of inflammatory cytokines was also observed in infected primary human corneal fibroblasts pretreated with a MyD88 inhibitory peptide. Keratitis similar to wild type mice was observed in TLR2, TLR9 and IL-1R knockout mice, but was reduced in TLR2/9 double knockout mice, consistent with synergy of TLR2 and TLR9 in the response to adenovirus infection. MyD88 co-immunoprecipitated with Src kinase in mice corneas and in human corneal fibroblasts infected with adenovirus, and MyD88 inhibitory peptide reduced Src phosphorylation, linking MyD88 activation to inflammatory gene expression through a signaling cascade previously shown to be directed by Src. Our findings reveal a critical role for the PRRs TLR2 and 9, and their adaptor protein MyD88, in corneal inflammation upon adenovirus infection.},
	issn = {1440-1711},
	doi = {10.1038/icb.2016.73},
	author = {Zhou, Xiaohong and Ramke, Mirja and Chintakuntlawar, Ashish V and Lee, Jeong Yoon and Rajaiya, Jaya and Chodosh, James}
}
@article {1677816,
	title = {Response to "Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany"},
	journal = {Arthritis Res Ther},
	volume = {25},
	number = {1},
	year = {2023},
	month = {2023 Mar 14},
	pages = {41},
	abstract = {We have read the article entitled "Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany" by Heiligenhaus et al. While we appreciate the work conducted by the authors, we have several comments we would like to address. First, the follow-up interval of 2\&nbsp;years is too short to conclude that the clinical course between two chronic pathologies is not significantly different. Second, remission status was determined by uveitis inactivity during the 2-year follow-up visit without any mention of flare frequency or length of remission, which is not a reliable measure of uveitis control. Third, ANA-positive idiopathic anterior uveitis is not a classification with a distinct clinical phenotype, and additional reports of serologic investigations would have been helpful.},
	keywords = {Arthritis, Juvenile, Disease Progression, Germany, Humans, Uveitis, Uveitis, Anterior},
	issn = {1478-6362},
	doi = {10.1186/s13075-023-03021-x},
	author = {Zhou, Avery and Babiker, Fatima and Philip, Andrew M and Anesi, Stephen D and Foster, C Stephen}
}
@article {1748431,
	title = {Opposing Roles of Blood-Borne Monocytes and Tissue-Resident Macrophages in Limbal Stem Cell Damage after Ocular Injury},
	journal = {Cells},
	volume = {12},
	number = {16},
	year = {2023},
	month = {2023 Aug 18},
	abstract = {Limbal stem cell (LSC) deficiency is a frequent and severe complication after chemical injury to the eye. Previous studies have assumed this is mediated directly by the caustic agent. Here we show that LSC damage occurs through immune cell mediators, even without direct injury to LSCs. In particular, pH elevation in the anterior chamber (AC) causes acute uveal stress, the release of inflammatory cytokines at the basal limbal tissue, and subsequent LSC damage and death. Peripheral C-C chemokine receptor type 2 positive/CX3C motif chemokine receptor 1 negative (CCR2+ CX3CR1-) monocytes are the key mediators of LSC damage through the upregulation of tumor necrosis factor-alpha (TNF-α) at the limbus. In contrast to peripherally derived monocytes, CX3CR1+ CCR2- tissue-resident macrophages have a protective role, and their depletion prior to injury exacerbates LSC loss and increases LSC vulnerability to TNF-α-mediated apoptosis independently of CCR2+ cell infiltration into the tissue. Consistently, repopulation of the tissue by new resident macrophages not only restores the protective M2-like phenotype of macrophages but also suppresses LSC loss after exposure to inflammatory signals. These findings may have clinical implications in patients with LSC loss after chemical burns or due to other inflammatory conditions.},
	keywords = {Eye Injuries, Humans, Limbal Stem Cell Deficiency, Limbal Stem Cells, Macrophages, Monocytes, Receptors, Chemokine, Tumor Necrosis Factor-alpha},
	issn = {2073-4409},
	doi = {10.3390/cells12162089},
	author = {Zhou, Chengxin and Lei, Fengyang and Mittermaier, Mirja and Ksander, Bruce and Dana, Reza and Dohlman, Claes H and Vavvas, Demetrios G and Chodosh, James and Paschalis, Eleftherios I}
}
@article {988061,
	title = {Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {58},
	number = {1},
	year = {2017},
	pages = {96-105},
	abstract = {Purpose: Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-α antibodies using a polymer-based drug delivery system (DDS). Methods: The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 μg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-α DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months. Results: After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-α expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation. Conclusions: This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation.},
	issn = {1552-5783},
	doi = {10.1167/iovs.16-20339},
	author = {Zhou, Chengxin and Robert, Marie-Claude and Kapoulea, Vassiliki and Lei, Fengyang and Stagner, Anna M and Jakobiec, Frederick A and Dohlman, Claes H and Paschalis, Eleftherios I}
}
@article {1698351,
	title = {Vision Outcomes of Long-Term Immunomodulatory and Steroid Therapy in Sympathetic Ophthalmia},
	journal = {Am J Ophthalmol},
	volume = {253},
	year = {2023},
	month = {2023 Sep},
	pages = {152-159},
	abstract = {PURPOSE: To compare vision acuity outcomes of long-term steroid therapy compared with immunomodulatory therapy for treatment of sympathetic ophthalmia. DESIGN: Single-center, retrospective, comparative clinical study. METHODS: Patients with sympathetic ophthalmia treated from March 2005 to October 2022 with at least 1 year of follow-up were included. Visual acuity outcomes were compared by steroid and immunomodulatory treatment modality. RESULTS: Thirty-five patients with sympathetic ophthalmia were included in the study, with follow-up ranging from 1 to 17 years. Higher rates of vision loss correlated with longer periods of active uveitis and steroid treatment. Lower rates of vision loss correlated with longer periods of uveitis remission on immunomodulatory therapy alone and drug-free remission. Treatment with alkylating agents or combination therapy with an antimetabolite, a biologic-response modifier, and cyclosporine are more likely to result in sympathetic ophthalmia remission. CONCLUSION: Immunomodulatory therapy leads to superior vision outcomes in cases of steroid-resistant or recurrent sympathetic ophthalmia. Steroid therapy may be useful for acute or recalcitrant sympathetic uveitis but is insufficient for long-term inflammatory control. PR{\'e}CIS: This manuscript describes a retrospective analysis of vision outcomes in patients with sympathetic ophthalmia. Results indicate that long-term immunomodulatory therapy is associated with better vision outcomes than long-term steroid therapy for sympathetic ophthalmia treatment.},
	keywords = {Cyclosporine, Glucocorticoids, Humans, Immunosuppressive Agents, Ophthalmia, Sympathetic, Retrospective Studies},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2023.05.004},
	author = {Zhou, Yujia and Zhou, Avery and Philip, Andrew M and Margolis, Michael and Babiker, Fatima and Chang, Peter Y and Anesi, Stephen D and Foster, C Stephen}
}
@article {1364579,
	title = {Analysis of human adenovirus type 19 associated with epidemic keratoconjunctivitis and its reclassification as adenovirus type 64},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {6},
	year = {2012},
	month = {2012 May 14},
	pages = {2804-11},
	abstract = {PURPOSE: Human adenovirus species D type 19 (HAdV-D19) has been associated with epidemic keratoconjunctivitis (EKC), a highly inflammatory infection of the ocular surface. Confusion exists regarding the origins of HAdV-D19. The prototype virus (HAdV-D19p) does not cause EKC, while a virus identified later with the identical serologic determinant is a significant ocular pathogen. METHODS: High throughput genome sequencing and bioinformatics analysis were performed on HAdV-D19p and three HAdV-D19 EKC strains, and compared to the previously sequenced clinical isolate, HAdV-D19 (C) and HAdV-D37. Corneas of C57BL/6J mice were injected with HAdV-D19p, HAdV-D19 (C), or virus-free buffer, and inflammation assessed by clinical examination, flow cytometry, and cytokine ELISA. Confocal microscopy and real-time PCR of infected corneal cell cultures were used to test viral entry. RESULTS: HAdV-D19 (C) and the other clinical EKC isolates showed nearly 100\% sequence identity. EKC strains diverged from HAdV-D19p in the penton base, E3, and fiber transcription units. Simplot analysis showed recombination between EKC-associated HAdV-D19 with HAdV-D37, HAdV-D22, and HAdV-D19p, the latter contributing only the hexon gene, the principal serum neutralization determinant. HAdV-D19p induced stromal keratitis in the C57BL/6J mouse, but failed to infect productively human corneal epithelial cells. These data led to retyping of the clinical EKC isolates with a HAdV-D19 hexon gene as HAdV-D64. CONCLUSIONS: HAdV-D19 associated with EKC (HAdV-D64) originated from a recombination between HAdV-D19p, HAdV-D37, and HAdV-D22, and was mischaracterized because of a shared hexon gene. HAdV-D19p is not infectious for corneal epithelial cells, thus explaining the lack of any association with keratitis.},
	keywords = {Adenovirus Infections, Human, Adenoviruses, Human, Animals, DNA, Viral, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Genome, Viral, Humans, Keratoconjunctivitis, Mice, Mice, Inbred C57BL, Sequence Analysis, DNA},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-9656},
	author = {Zhou, Xiaohong and Robinson, Christopher M and Rajaiya, Jaya and Dehghan, Shoaleh and Seto, Donald and Jones, Morris S and Dyer, David W and Chodosh, James}
}
@article {1603846,
	title = {Absence of ephrin-A2/A3 increases retinal regenerative potential for M{\"u}ller cells in Rhodopsin knockout mice},
	journal = {Neural Regen Res},
	volume = {16},
	number = {7},
	year = {2021},
	month = {2021 Jul},
	pages = {1317-1322},
	abstract = {M{\"u}ller cells (MC) are considered dormant retinal progenitor cells in mammals. Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain. It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC. Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of M{\"u}ller cells. In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC. The level of ephrinAs/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC. Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2-/- A3-/- mice by 5-ethynyl-2{\textquoteright}-deoxyuridine (EdU) incorporation. We detected a significant increase of EdU+ cells in MC derived from A2-/- A3-/- mice. Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout (Rho-/-) mice. To further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2-/- A3-/- , Rho-/- and Rho-/- A2-/- A3-/- mice and the numbers of EdU+ cells distributed among different layers of the retina. EphrinAs/EphA4 expression was upregulated in the retina of Rho-/- mice compared to the wild-type mice. In addition, cultured MC derived from ephrin-A2-/- A3-/- mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type mice. Interestingly, we detected a significant increase of EdU+ cells in the retinas of adult ephrin-A2-/- A3-/- mice mainly in the inner nuclear layer; and these EdU+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from MC. In Rhodopsin knockout mice (Rho-/- A2-/- A3-/- mice), a significantly greater amount of EdU+ cells were located in the ciliary body, retina and RPE than that of Rho-/- mice. Comparing between 6 and 12 weeks old Rho-/- A2-/- A3-/- mice, we recorded more EdU+ cells in the outer nuclear layer in the 12-week-old mice undergoing severe retinal degeneration. Taken together, Ephrin-A2/A3 are negative regulators of the proliferative and neurogenic potentials of MC. Absence of ephrin-A2/A3 promotes the migration of proliferating cells into the outer nuclear layer and may lead to retinal cell regeneration. All experimental procedures were approved by the Animal Care and Use Committee at Schepens Eye Research Institute, USA (approval No. S-353-0715) on October 24, 2012.},
	issn = {1673-5374},
	doi = {10.4103/1673-5374.301034},
	author = {Zhu, Rui-Lin and Fang, Yuan and Yu, Hong-Hua and Chen, Dong F and Yang, Liu and Cho, Kin-Sang}
}
@article {303901,
	title = {Ephrin-A2 and -A3 are negative regulators of the regenerative potential of M{\"o}ller cells},
	journal = {Chin Med J (Engl)},
	volume = {127},
	number = {19},
	year = {2014},
	month = {2014},
	pages = {3438-42},
	abstract = {BACKGROUND: In a previous study, we demonstrated that ephrin-A2 and -A3 negatively regulate the growth of neural progenitor cells in the central nervous system. Adult mice deficient in ephrin-A2 and -A3 (A2(-/-)A3(-/-)) displayed active ongoing neurogenesis throughout the brain, and mice deficient in ephrin-A3 alone showed increased proliferation of ciliary epithelium derived retinal stem cells. This study aimed to detect that the increase in proliferation and neurogenic potential of M{\"u}ller cells is influenced by the absence of ephrin-A2 and -A3. METHODS: We assessed the retinal and M{\"u}ller cell expression of ephrin-As and their receptor and neural progenitor cell markers by immunostaining and real-time PCR. We cultured purified primary M{\"u}ller cells derived from wild-type and A2(-/-)A3(-/-) mice in a defined culture medium that enables trans-differentiation of M{\"u}ller cells into retinal neurons. To evaluate proliferating M{\"u}ller cells in vivo, we injected 5{\textquoteright}-ethylnyl-2{\textquoteright}-deoxiuridine (EdU) intraperitoneally to adult mice. RESULTS: Expression of ephrin-A2/A3 and their receptor EphA4 were detected in the retinas of adult mice, with EphA4 expression particularly enriched in M{\"u}ller cells. M{\"u}ller cells of A2(-/-)A3(-/-) mice exhibited significantly elevated expression of retinal progenitor cell markers, Pax6 and Chx10, when compared with those from wild-type mice. Moreover, a higher percentage of M{\"u}ller cells of A2(-/-)A3(-/-) mice trans-differentiated and became recoverin+ and β-III-tublin+ in the culture than those from wild type mice. Strikingly, an increased number of EdU+ retinal cells was detected in the retinas of adult A2(-/-)A3(-/-) mice as compared with wild-type mice. CONCLUSIONS: Ephrin-A2 and -A3 are negative regulators of the proliferative and neurogenic potentials of M{\"u}ller cells. Manipulating ephrin-A signaling may thus represent a novel strategy for stimulating neuroregeneration from endogenous progenitors to participate in retinal repair in case of disease or damage.},
	keywords = {Animals, Cell Differentiation, Ephrin-A2, Ephrin-A3, Fluorescent Antibody Technique, Mice, Mice, Inbred C57BL, Mice, Knockout, Real-Time Polymerase Chain Reaction, Receptor, EphA4, Retina, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells},
	issn = {0366-6999},
	author = {Zhu, Ruilin and Cho, Kin-Sang and Chen, Dong Feng and Yang, Liu}
}
@article {753686,
	title = {Corneal Crosslinking With Rose Bengal and Green Light: Efficacy and Safety Evaluation.},
	journal = {Cornea},
	volume = {35},
	number = {9},
	year = {2016},
	month = {2016 Sep},
	pages = {1234-41},
	abstract = {PURPOSE: To evaluate crosslinking of cornea in vivo using green light activation of Rose Bengal (RGX) and assess potential damaging effects of the green light on retina and iris. METHODS: Corneas of Dutch belted rabbits were de-epithelialized, then stained with Rose Bengal and exposed to green light, or not further treated. Corneal stiffness was measured by uniaxial tensiometry. Re-epithelialization was assessed by fluorescein fluorescence. Keratocytes were counted on hematoxylin and eosin (H\&amp;E)-stained sections, and iris cell damage was assessed by lactate dehydrogenase staining. Thermal effects on the blood-retinal barrier (BRB) were assessed by fluorescein angiography and those on photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris by light microscopy and transmission electron microscopy. RESULTS: RGX (10-min irradiation; 150 J/cm) increased corneal stiffness 1.9-fold on day 1 (1.25 {\textpm} 0.21 vs. 2.38 {\textpm} 0.59 N/mm; P = 0.036) and 2.8-fold compared with controls on day 28 (1.70 {\textpm} 0.74 vs. 4.95 {\textpm} 1.86 N/mm; P = 0.003). Keratocytes decreased only in the anterior stroma on day 1 (24.0 {\textpm} 3.0 vs. 3.67 {\textpm} 4.73, P = 0.003) and recovered by day 28 (37.7 {\textpm} 8.9 vs. 34.5 {\textpm} 2.4, P = 0.51). Iris cells were not thermally damaged. No evidence of BRB breakdown was detected on days 1 or 28. Retina from RGX-treated eyes seemed normal with RPE cells showing intact nuclei shielded apically by melanosomes, morphologically intact photoreceptor outer segments, normal outer nuclear layer thickness, and choriocapillaris containing intact erythrocytes. CONCLUSIONS: The substantial corneal stiffening produced by RGX together with the lack of significant effects on keratocytes and no evidence for retina or iris damage suggest that RGX-initiated corneal crosslinking may be a safe, rapid, and effective treatment.},
	issn = {1536-4798},
	doi = {10.1097/ICO.0000000000000916},
	author = {Zhu, Hong and Alt, Clemens and Webb, Robert H and Melki, Samir and Kochevar, Irene E}
}
@article {1460383,
	title = {Meeting the need for corrective spectacles in visually impaired Chinese school children: the potential of ready-made spectacles},
	journal = {Br J Ophthalmol},
	volume = {103},
	number = {8},
	year = {2019},
	month = {2019 Aug},
	pages = {1106-1111},
	abstract = {PURPOSE: To assess the potential of ready-made (spherical) spectacles (RMS) in meeting the need for refractive correction in visually impaired children in China. METHODS: Eligible children aged 5-17 years were identified from the three study sites in China. Distance visual acuity was measured with a retroilluminated logarithm of the minimum angle of resolution chart with tumbling E optotypes. Cycloplegic autorefraction was performed on all children using a handheld autorefractor. If uncorrected visual acuity (UCVA) was <=20/40 in either eye, best corrected visual acuity was measured with subjective refractive error. RESULTS\&nbsp;: A total of 13 702 children were enumerated from the three studies, with 12 334 (90.0\%) having both reliable visual acuity measurements and successful cycloplegia. Among the 12 334 study children, the prevalence of UCVA <=20/40 in the better seeing eye was 16.4\% (95\% CI 15.0\% to 17.8\%), with 91.1\% (1843) of these improving by >=3 lines of visual acuity with refractive correction. Prevalence was 12.7\% (95\% CI 11.5\% to 13.9\%) for UCVA 20/50 with 97.4\% (1521) improving by >=3 lines, and 9.38\% (95\% CI 8.39\% to 19.4\%) for UCVA <=20/63 with 98.4\% (1138) improving by >=3 lines. Depending on the severity of visual impairment, 62.8\%-64.0\% of children could be accommodated with RMS if not correcting for astigmatism of <=0.75 dioptres and anisometropia of <=0.50 spherical equivalent dioptres. Approximately 87\% of children could be accommodated with RMS if astigmatism and anisometropia limits were increased to <=1.25 and <=1.50 dioptres, respectively. CONCLUSIONS: RMS could substantially alleviate visual morbidity in two-thirds or more of visually impaired schoolchildren in China. This cost-effective approach to refractive correction might also be useful in low/middle-income countries with poor access to optometric services.},
	issn = {1468-2079},
	doi = {10.1136/bjophthalmol-2018-312262},
	author = {Zhu, Zhuoting and Ellwein, Leon B and Wang, Sean K and Zhao, Jialiang and He, Mingguang}
}
@article {1498243,
	title = {Different Scan Protocols Affect the Detection Rates of Diabetic Retinopathy Lesions by Wide-Field Swept-Source Optical Coherence Tomography Angiography},
	journal = {Am J Ophthalmol},
	volume = {215},
	year = {2020},
	month = {2020 Jul},
	pages = {72-80},
	abstract = {PURPOSE: To compare different scan protocols of wide-field swept-source optical coherence tomography angiography (SS-OCTA) for the detection of diabetic retinopathy (DR) lesions. DESIGN: Comparison of diagnostic approaches. METHODS: A prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to July 2019. Proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), and diabetic patients without DR were included. All patients were imaged using SS-OCTA using the following scan protocol: 3-\&nbsp;{\texttimes} 3-mm Angio centered on the fovea; 6-\&nbsp;{\texttimes} 6-mm Angio centered on the fovea and the optic disc; 15-\&nbsp;{\texttimes} 9-mm Montage; and 12-\&nbsp;{\texttimes} 12-mm Angio centered on the fovea and the optic disc. Images were independently evaluated by 2 graders for the presence or absence of DR lesions including microaneurysms, intraretinal microvascular abnormalities, neovascularization, nonperfusion areas, venous looping, and hard exudates. All statistical analyses were performed using commercial software. RESULTS: A total of 176 eyes in 119 participants were included in the study. The detection rate of neovascularization on 6-\&nbsp;{\texttimes} 6-mm Angio centered on the fovea was approximately one-half that on 15-\&nbsp;{\texttimes} 9-mm Montage (P \&lt; .05) imaging. Combining 6-\&nbsp;{\texttimes} 6-mm Angio imaging centered on the fovea and the optic disc could increase the rate to approximately two-thirds (P \&lt; .05). The 12-\&nbsp;{\texttimes} 12-mm Angio imaging centered on the combination of fovea and optic disc had detection rates comparable to those of 15-\&nbsp;{\texttimes} 9-mm Montage imaging for all DR lesions (P \&gt; .05). For microaneurysms, 6-\&nbsp;{\texttimes} 6-mm Angio had better performance than 15-\&nbsp;{\texttimes} 9-mm Montage (P \&lt; .05). CONCLUSIONS: Wide-field SS-OCTA images were useful in detecting DR lesions. The 12-\&nbsp;{\texttimes} 12-mm Angio imaging centered on the fovea and on the optic disc may\&nbsp;be an optimal balance between speed and efficacy for evaluation of DR in clinical practice.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2020.03.004},
	author = {Zhu, Ying and Cui, Ying and Wang, Jay C and Lu, Yifan and Zeng, Rebecca and Katz, Raviv and Wu, David M and Eliott, Dean and Vavvas, Demetrios G and Husain, Deeba and Miller, Joan W and Kim, Leo A and Miller, John B}
}
@article {1642014,
	title = {Promotion of corneal angiogenesis by sensory neuron-derived calcitonin gene-related peptide},
	journal = {Exp Eye Res},
	volume = {220},
	year = {2022},
	month = {2022 Jul},
	pages = {109125},
	abstract = {The normal cornea has no blood vessels but has abundant innervation. There is emerging evidence that sensory nerves, originated from the trigeminal ganglion (TG) neurons, play a key role in corneal angiogenesis. In the current study, we examined the role of TG sensory neuron-derived calcitonin gene-related peptide (CGRP) in promoting corneal neovascularization (CNV). We found that CGRP was expressed in the TG and cultured TG neurons. In the cornea, minimal CGRP mRNA was detected and CGRP immunohistochemical staining was exclusively co-localized with corneal nerves, suggesting corneal nerves are likely the source of CGRP in the cornea. In response to intrastromal suture placement and neovascularization in the cornea, CGRP expression was increased in the TG. In addition, we showed that CGRP was potently pro-angiogenic, leading to vascular endothelial cell (VEC) proliferation, migration, and tube formation in vitro and corneal hemangiogenesis and lymphangiogenesis in vivo. In a co-culture system of TG neurons and VEC, blocking CGRP signaling in the conditioned media of TG neurons led to decreased VEC migration and tube formation. More importantly, subconjunctival injection of a CGRP antagonist CGRP8-37 reduced suture-induced corneal hemangiogenesis and lymphangiogenesis in vivo. Taken together, our data suggest that TG sensory neuron and corneal nerve-derived CGRP promotes corneal angiogenesis.},
	keywords = {Calcitonin Gene-Related Peptide, Cornea, Corneal Neovascularization, Humans, Sensory Receptor Cells, Trigeminal Ganglion},
	issn = {1096-0007},
	doi = {10.1016/j.exer.2022.109125},
	author = {Zhu, Shuyan and Zidan, Asmaa and Pang, Kunpeng and Musayeva, Aytan and Kang, Qianyan and Yin, Jia}
}
@article {1593829,
	title = {Innate Immune Invisible Ultrasmall Gold Nanoparticles-Framework for Synthesis and Evaluation},
	journal = {ACS Appl Mater Interfaces},
	volume = {13},
	number = {20},
	year = {2021},
	month = {2021 May 26},
	pages = {23410-23422},
	abstract = {Nanomedicine is seen as a potential central player in the delivery of personalized medicine. Biocompatibility issues of nanoparticles have largely been resolved over the past decade. Despite their tremendous progress, less than 1\% of applied nanosystems can hit their intended target location, such as a solid tumor, and this remains an obstacle to their full ability and potential with a high translational value. Therefore, achieving immune-tolerable, blood-compatible, and biofriendly nanoparticles remains an unmet need. The translational success of nanoformulations from bench to bedside involves a thorough assessment of their design, compatibility beyond cytotoxicity such as immune toxicity, blood compatibility, and immune-mediated destruction/rejection/clearance profile. Here, we report a one-pot process-engineered synthesis of ultrasmall gold nanoparticles (uGNPs) suitable for better body and renal clearance delivery of their payloads. We have obtained uGNP sizes of as low as 3 nm and have engineered the synthesis to allow them to be accurately sized (almost nanometer by nanometer). The synthesized uGNPs are biocompatible and can easily be functionalized to carry drugs, peptides, antibodies, and other therapeutic molecules. We have performed in vitro cell viability assays, immunotoxicity assays, inflammatory cytokine analysis, a complement activation study, and blood coagulation studies with the uGNPs to confirm their safety. These can help to set up a long-term safety-benefit framework of experimentation to reveal whether any designed nanoparticles are immune-tolerable and can be used as payload carriers for next-generation vaccines, chemotherapeutic drugs, and theranostic agents with better body clearance ability and deep tissue penetration.},
	issn = {1944-8252},
	doi = {10.1021/acsami.1c02834},
	author = {Zhu, Geyunjian Harry and Azharuddin, Mohammad and Islam, Rakibul and Rahmoune, Hassan and Deb, Suryyani and Kanji, Upasona and Das, Jyotirmoy and Osterrieth, Johannes and Aulakh, Parminder and Ibrahim-Hashi, Hashi and Manchanda, Raghav and Nilsson, Per H and Mollnes, Tom Eirik and Bhattacharyya, Maitreyee and Islam, Mohammad M and Hinkula, Jorma and Slater, Nigel K H and Patra, Hirak K}
}
@article {1328910,
	title = {Ultrastructural Morphology of the Optic Nerve Head in Aged and Glaucomatous Mice},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {59},
	number = {10},
	year = {2018},
	month = {2018 Aug 01},
	pages = {3984-3996},
	abstract = {Purpose: To study age- and intraocular pressure-induced changes in the glial lamina of the murine optic nerve on the ultrastructural level. Methods: Na{\"\i}ve C57bl/6 mice at various ages spanning the time between early adulthood (3 months) and senescence (30 months) were used in this study. In addition, the intraocular pressure (IOP) was increased in a group of young mice by injection of microbeads into the anterior chamber. The unmyelinated segments of the optic nerve containing the glial lamina were prepared for transmission electron microscopy and imaged at high resolution. Results: Axon packing density decreased slightly with age. Aging nerves contained higher numbers of enlarged and degenerating axons. Mean axonal diameter and in particular the variance of axonal diameter correlated well with age. Axonal mitochondria also showed age-dependent signs of pathology. The mean diameter of axonal mitochondria increased, and aged axons often contained profiles of mitochondria with very few or no cristae. Astrocytic mitochondria remained normal even in very old nerves. Changes to axons and axonal mitochondria in young glaucomatous nerves were comparable with those of 18- to 30-month-old na{\"\i}ve mice. In addition to axons and mitochondria, aged and glaucomatous nerves showed thickening of the blood vessel basement membranes and increased deposition of basement membrane collagen. Conclusions: On the ultrastructural level, the effects of age and elevated IOP are quite similar. One month of elevated IOP seems to have as strongly detrimental effects on the nerve as at least 18 months of normal aging.},
	issn = {1552-5783},
	doi = {10.1167/iovs.18-23885},
	author = {Zhu, Ying and Pappas, Anthony C and Wang, Rui and Seifert, Philip and Sun, Daniel and Jakobs, Tatjana C}
}
@article {1651346,
	title = {Comparison of hyperreflective foci in macular edema secondary to multiple etiologies with spectral-domain optical coherence tomography: An observational study},
	journal = {BMC Ophthalmol},
	year = {2022},
	author = {Zhu, R and Xiao, S and Zhang, W. and Li, J. and Yang, M and Zhang, Y. and Gu, X. and Yang, L}
}
@article {1363237,
	title = {Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal dystrophy: a novel treatment},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {54},
	number = {10},
	year = {2013},
	month = {2013 Oct 15},
	pages = {6724-34},
	abstract = {PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is an oxidative stress disorder that leads to age-related and gradual loss of corneal endothelial cells resulting in corneal edema and loss of vision. To date, other than surgical intervention, there are no treatment options for patients with FECD. We have shown that in FECD, there is a deficiency in nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated antioxidant defense due to decreased Nrf2 nuclear translocation and activation of antioxidant response element (ARE). In this study, we used sulforaphane (SFN) and D3T to investigate a strategy of targeting Nrf2-ARE in FECD. METHODS: FECD and normal ex vivo corneas and human corneal endothelial cell lines were pretreated with SFN or D3T and exposed to oxidative stress with tert-Butyl hydroperoxide (tBHP). Apoptosis was detected with TUNEL. Cellular localization of Nrf2 and p53 was assessed by immunohistochemistry. Effect of SFN was determined by using DCFDA assay, Western blot and real-time PCR. RESULTS: After pretreatment with SFN, oxidative stress was induced with tBHP. In ex vivo FECD specimens, SFN decreased CEC apoptosis by 55\% in unstressed group and by 43\% in tBHP-treated specimens. SFN enhanced nuclear translocation of Nrf2 in FECD specimens and decreased p53 staining under oxidative stress. Pretreatment with SFN enhanced cell viability by decreasing intracellular reactive oxygen species production. Upregulation of Nrf2 levels led to increased synthesis of DJ-1, heme oxygenase 1, and nicotinamide adenine dinucleotide quinone oxidoreductase-1. SFN significantly upregulated major ARE-dependent antioxidants and ameliorated oxidative stress-induced apoptosis in FECD. CONCLUSIONS: Our results suggest that targeting Nrf2-ARE pathway may arrest degenerative cell loss seen in FECD.},
	keywords = {Aged, Anticarcinogenic Agents, Apoptosis, Blotting, Western, Cell Line, Corneal Transplantation, Endothelium, Corneal, Female, Fuchs{\textquoteright} Endothelial Dystrophy, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Isothiocyanates, Male, NF-E2-Related Factor 2, Oxidative Stress, Real-Time Polymerase Chain Reaction, RNA, Up-Regulation},
	issn = {1552-5783},
	doi = {10.1167/iovs.13-12699},
	author = {Ziaei, Alireza and Schmedt, Thore and Chen, Yuming and Jurkunas, Ula V}
}
@article {1789056,
	title = {Incidental finding of a retained intracorneal wooden foreign body},
	journal = {BMJ Case Rep},
	volume = {16},
	number = {12},
	year = {2023},
	month = {2023 Dec 11},
	abstract = {We present a case of an intracorneal wooden foreign body that remained undetected for 15 years following an ocular injury sustained during gardening. The patient presented with stable visual acuity despite the long-standing presence of a wooden splinter embedded in the cornea. Interestingly, Pentacam corneal tomography did not show any abnormalities despite the foreign body piercing through the corneal stroma and endothelium. This case may serve as an opportunity to re-examine the approach to managing chronic and stable intracorneal wooden foreign bodies and explore the implications of continued observation rather than surgical management.},
	keywords = {Cornea, Corneal Stroma, Eye Foreign Bodies, Eye Injuries, Penetrating, Humans, Incidental Findings},
	issn = {1757-790X},
	doi = {10.1136/bcr-2023-258340},
	author = {Zidan, Asmaa and Barbosa, Joshua and Diskin, Jacob and McDermott, Mark}
}
@article {1439869,
	title = {Extracellular Vesicles and Cell-Cell Communication in the Cornea},
	journal = {Anat Rec (Hoboken)},
	volume = {303},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {1727-1734},
	abstract = {One question that has intrigued cell biologists for many years is, "How do cells interact to influence one another{\textquoteright}s activity?" The discovery of extracellular vesicles (EVs) and the fact that they carry cargo, which directs cells to undergo changes in morphology and gene expression, has revolutionized this field of research. Little is known regarding the role of EVs in the cornea; however, we have demonstrated that EVs isolated from corneal epithelial cells direct corneal keratocytes to initiate fibrosis. Intriguingly, our data suggest that EVs do not penetrate epithelial basement membrane (BM), perhaps providing a mechanism explaining the importance of BM in the lack of scarring in scrape wounds. Since over 100-million people worldwide suffer from visual impairment as a result of corneal scarring, the role of EVs may be vital to understanding the mechanisms of wound repair. Therefore, we investigated EVs in ex vivo and in vivo-like three-dimensional cultures of human corneal cells using transmission electron microscopy. Some of the major findings were all three major cell types (epithelial, fibroblast, and endothelial cells) appear to release EVs, EVs can be identified using TEM, and EVs appeared to be involved in cell-cell communication. Interestingly, while our previous publication suggests that EVs do not penetrate the epithelial BM, it appears that EVs penetrate the much thicker endothelial BM (Descemet{\textquoteright}s membrane). These findings indicate the huge potential of EV research in the cornea and wound healing, and suggest that during homeostasis the endothelium and stromal cells are in communication. Anat Rec, 2019. {\textcopyright} 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.},
	issn = {1932-8494},
	doi = {10.1002/ar.24181},
	author = {Zieske, James D and Hutcheon, Audrey E K and Guo, Xiaoqing}
}
@article {1658664,
	title = {Ancestral library identifies conserved reprogrammable liver motif on AAV capsid},
	journal = {Cell Rep Med},
	volume = {3},
	number = {11},
	year = {2022},
	month = {2022 Nov 15},
	pages = {100803},
	abstract = {Gene therapy is emerging as a modality in 21st-century medicine. Adeno-associated viral (AAV) gene transfer is a leading technology to achieve efficient and durable expression of a therapeutic transgene. However, the structural complexity of the capsid has constrained efforts to engineer the particle toward improved clinical safety and efficacy. Here, we generate a curated library of barcoded AAVs with mutations across a variety of functionally relevant motifs. We then screen this library in\&nbsp;vitro and in\&nbsp;vivo in mice and nonhuman primates, enabling a broad, multiparametric assessment of every vector within the library. Among the results, we note a single residue that modulates liver transduction across all interrogated models while preserving transduction in heart and skeletal muscles. Moreover, we find that this mutation can be grafted into AAV9 and leads to profound liver detargeting while retaining muscle transduction-a finding potentially relevant to preventing hepatoxicities seen in clinical studies.},
	keywords = {Animals, Capsid, Capsid Proteins, Dependovirus, Genetic Vectors, Liver, Mice},
	issn = {2666-3791},
	doi = {10.1016/j.xcrm.2022.100803},
	author = {Zinn, Eric and Unzu, Carmen and Schmit, Pauline F and Turunen, Heikki T and Zabaleta, Nerea and Sanmiguel, Julio and Fieldsend, Allegra and Bhatt, Urja and Diop, Cheikh and Merkel, Erin and Gurrala, Rakesh and Peacker, Bryan and Rios, Christopher and Messemer, Kathleen and Santos, Jennifer and Estelien, Reynette and Andres-Mateos, Eva and Wagers, Amy J and Tipper, Christopher and Vandenberghe, Luk H}
}
@article {503921,
	title = {In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector.},
	journal = {Cell Rep},
	volume = {12},
	number = {6},
	year = {2015},
	month = {2015 Aug 11},
	pages = {1056-68},
	abstract = {Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the\&nbsp;complex multimeric icosahedral architecture of\&nbsp;the particle. To develop additional reagents pertinent to\&nbsp;further our insight into AAVs, we inferred evolutionary intermediates of the viral capsid using ancestral sequence reconstruction. In-silico-derived sequences were synthesized de novo and characterized for biological properties relevant to clinical applications. This effort led to the generation of nine functional putative ancestral AAVs and the identification of Anc80, the predicted ancestor of the widely studied AAV serotypes 1, 2, 8, and 9, as a highly potent in\&nbsp;vivo gene therapy vector for targeting liver, muscle, and retina.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2015.07.019},
	author = {Zinn, Eric and Pacouret, Simon and Khaychuk, Vadim and Turunen, Heikki T and Carvalho, Livia S and Andres-Mateos, Eva and Shah, Samiksha and Shelke, Rajani and Maurer, Anna C and Plovie, Eva and Xiao, Ru and Vandenberghe, Luk H}
}
@article {303921,
	title = {Adeno-associated virus: fit to serve.},
	journal = {Curr Opin Virol},
	volume = {8C},
	year = {2014},
	month = {2014 Oct},
	pages = {90-97},
	abstract = {Adeno-associated virus (AAV) is a helper-dependent parvovirus which has not been linked with human disease. This aspect, in combination with its broad cell and tissue tropism, and limited viral host response has made it an attractive vector system for gene therapy. The viral protein capsid, the primary interface with the host, is the main determinant for these phenotypes, is highly variable, and is most subject to pressures during replication. Here, we explore the evolutionary path of AAV and other parvoviruses in respect to these phenotypes, as well as directed evolution and engineering strategies that have exploited the lessons learned from natural selection in order to address remaining limitations of AAV as a therapeutic gene transfer platform.},
	issn = {1879-6265},
	doi = {10.1016/j.coviro.2014.07.008},
	author = {Zinn, Eric and Vandenberghe, Luk H}
}
@article {1629455,
	title = {AAV capsid design: A Goldilocks challenge},
	journal = {Trends Mol Med},
	volume = {28},
	number = {3},
	year = {2022},
	month = {2022 03},
	pages = {183-193},
	abstract = {In vivo therapeutic gene transfer has emerged as a novel class of medicines. Its feasibility relies on the safe and efficacious delivery of genetic cargo to the appropriate targets. The adeno-associated virus (AAV) vector manifested itself as a preferred gene delivery vehicle enabling therapeutic gene expression for several clinical indications. Here, we cover the recent trends in AAV capsid engineering to enhance its targeting specificity, safety, and endurance. While each and every desirable trait can be individually remodeled, combining several attributes in one capsid amounts to a significant engineering challenge. Taking advantage of virion structure and phylogenetics, harnessing directed evolution, sequence analyses, and machine learning, researchers develop novel capsid variants to realize the goals of safe and enduring gene therapy.},
	issn = {1471-499X},
	doi = {10.1016/j.molmed.2022.01.003},
	author = {Zolotukhin, S and Vandenberghe, L H}
}
@article {1661839,
	title = {Floppy Eyelid Syndrome: an Overlooked Comorbidity Among Bariatric Patients},
	journal = {Obes Surg},
	volume = {33},
	number = {2},
	year = {2023},
	month = {2023 Feb},
	pages = {523-529},
	abstract = {PURPOSE: Floppy eyelid syndrome (FES) is a clinical entity characterized by palpebral hyperlaxity and chronic conjunctivitis. Patients{\textquoteright} eyelids evert ("flip inside out"), leading to eye irritation, dryness, grittiness, and tearing. More severe cases can lead to significant ocular complications, such as keratoconus and impaired eyesight. Research has revealed an association between FES and obstructive sleep apnea syndrome (OSAS). OSAS is also one of the most common comorbidities among patients with obesity and an indication for bariatric surgery. This is one of the first studies to explore FES in a group of patients who have undergone bariatric surgery. MATERIALS AND METHODS: This was a retrospective study. A total of 88 patients completed a survey by mail or telephone. Additional data on demographics and baseline preoperative clinical information was extracted from the online medical records and the MBSAQIP database. RESULTS: Thirty-nine patients (44\%) recalled having chronic ocular symptoms before their bariatric surgery, among whom six reported palpebral laxity and/or an established diagnosis of FES. The majority of them (67\%) rated their symptoms postoperatively as "somewhat" or "significantly improved." The patients that reported improvement in their ocular symptoms also experienced an improvement in their OSAS severity. CONCLUSION: Bariatric surgery might affect the clinical course of FES and the severity of symptoms. Treating OSAS, the underlying mechanism of FES, is a possible mechanism of how bariatric surgery can help patients. It is also critical for bariatric surgeons to consider FES when patients with obesity, particularly those with OSAS, present with chronic eye symptoms.},
	keywords = {Bariatrics, Comorbidity, Eyelid Diseases, Eyelids, Humans, Obesity, Obesity, Morbid, Retrospective Studies, Sleep Apnea, Obstructive, Syndrome},
	issn = {1708-0428},
	doi = {10.1007/s11695-022-06410-4},
	author = {Zoumpou, Theofano and Samuel, Sandy and Torun, Nurhan and Yadav, Prashant and Jones, Daniel B}
}
@article {1528427,
	title = {A connectomics approach to understanding a retinal disease},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	number = {31},
	year = {2020},
	month = {2020 Aug 04},
	pages = {18780-18787},
	abstract = {Macular telangiectasia type 2 (MacTel), a late-onset macular degeneration, has been linked to a loss in the retina of M{\"u}ller glial cells and the amino acid serine, synthesized by the M{\"u}ller cells. The disease is confined mainly to a central retinal region called the MacTel zone. We have used electron microscopic connectomics techniques, optimized for disease analysis, to study the retina from a 48-y-old woman suffering from MacTel. The major observations made were specific changes in mitochondrial structure within and outside the MacTel zone that were present in all retinal cell types. We also identified an abrupt boundary of the MacTel zone that coincides with the loss of M{\"u}ller cells and macular pigment. Since M{\"u}ller cells synthesize retinal serine, we propose that a deficiency of serine, required for mitochondrial maintenance, causes mitochondrial changes that underlie MacTel development.},
	issn = {1091-6490},
	doi = {10.1073/pnas.2011532117},
	author = {Zucker, Charles L and Bernstein, Paul S and Schalek, Richard L and Lichtman, Jeff W and Dowling, John E}
}
@article {1504054,
	title = {Cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	number = {19},
	year = {2020},
	month = {2020 May 12},
	pages = {10339-10349},
	abstract = {Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From \~{}24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque (), rhesus macaque (), pig (), and mouse (). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.},
	issn = {1091-6490},
	doi = {10.1073/pnas.2001250117},
	author = {van Zyl, Tav{\'e} and Yan, Wenjun and McAdams, Alexi and Peng, Yi-Rong and Karthik Shekhar and Regev, Aviv and Juric, Dejan and Sanes, Joshua R}
}
@article {1647896,
	title = {Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types},
	journal = {Proc Natl Acad Sci U S A},
	volume = {119},
	number = {29},
	year = {2022},
	month = {2022 Jul 19},
	pages = {e2200914119},
	abstract = {The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens, and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some disorders, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that compose these tissues, we generated an anterior segment cell atlas of the human eye using high-throughput single-nucleus RNA sequencing (snRNAseq). We profiled 195,248 nuclei from nondiseased anterior segment tissues of six human donors, identifying \&gt;60 cell types. Many of these cell types were discrete, whereas others, especially in the lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment, revealing that some cell types are unique to a single structure, whereas others are shared across tissues. The integrated cell atlas was then used to investigate cell type-specific expression patterns of more than 900 human ocular disease genes identified through either Mendelian inheritance patterns or genome-wide association studies.},
	keywords = {Adult, Aqueous Humor, Ciliary Body, Genome-Wide Association Study, Humans, Iris, Trabecular Meshwork},
	issn = {1091-6490},
	doi = {10.1073/pnas.2200914119},
	author = {van Zyl, Tav{\'e} and Yan, Wenjun and McAdams, Alexi M and Monavarfeshani, Aboozar and Hageman, Gregory S and Sanes, Joshua R}
}
@article {509131,
	title = {Vision Loss and Paresthesias in a Young Man.},
	journal = {JAMA Ophthalmol},
	volume = {133},
	number = {10},
	year = {2015},
	month = {2015 Oct 1},
	pages = {1207-8},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.1935},
	author = {van Zyl, Tav{\'e} and Papakostas, Thanos D and Sobrin, Lucia}
}
@article {688671,
	title = {An Atypical Ulcerated Lesion at the Eyelid Margin.},
	journal = {JAMA Ophthalmol},
	volume = {134},
	number = {6},
	year = {2016},
	month = {2016 Jun 1},
	pages = {703-4},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2015.4965},
	author = {van Zyl, Tav{\'e} and Stagner, Anna M and Lee, Nahyoung Grace}
}
@article {504061,
	title = {Histopathologic features of a resolving orbital Langerhans cell histiocytosis.},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {253},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {2341-3},
	issn = {1435-702X},
	doi = {10.1007/s00417-015-3086-z},
	author = {van Zyl, Tav{\'e} and Stagner, Anna M and Jakobiec, Frederick A and Yoon, Michael K}
}
