2021

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Wu W, Xia X, Tang L, Yao F, Xu H, Lei H. Normal vitreous promotes angiogenesis via activation of Axl. FASEB J 2021;35(1):e21152.Abstract
Vitreous has been reported to prevent tumor angiogenesis, but our previous findings indicate that vitreous activate the signaling pathway of phosphoinositide 3-kinase (PI3K)/Akt, which plays a critical role in angiogenesis. The goal of this research is to determine which role of vitreous plays in angiogenesis-related cellular responses in vitro. We found that in human retinal microvascular endothelial cells (HRECs) vitreous activates a number of receptor tyrosine kinases including Anexelekto (Axl), which plays an important role in angiogenesis. Subsequently, we discovered that depletion of Axl using CRISPR/Cas9 and an Axl-specific inhibitor R428 suppress vitreous-induced Akt activation and cell proliferation, migration, and tuber formation of HRECs. Therefore, this line of research not only demonstrate that vitreous promotes angiogenesis in vitro, but also reveal that Axl is one of receptor tyrosine kinases to mediate vitreous-induced angiogenesis in vitro, thereby providing a molecular basis for removal of vitreous as cleanly as possible when vitrectomy is performed in treating patients with proliferative diabetic retinopathy.
WuDunn D, Takusagawa HL, Sit AJ, Rosdahl JA, Radhakrishnan S, Hoguet A, Han Y, Chen TC. OCT Angiography for the Diagnosis of Glaucoma: A Report by the American Academy of Ophthalmology. Ophthalmology 2021;128(8):1222-1235.Abstract
PURPOSE: To review the current published literature on the use of OCT angiography (OCTA) to help detect changes associated with the diagnosis of primary open-angle glaucoma. METHODS: Searches of the peer-reviewed literature were conducted in March 2018, June 2018, April 2019, December 2019, and June 2020 in the PubMed and Cochrane Library databases. Abstracts of 459 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 75 articles were selected and the panel methodologist rated them for strength of evidence. Three articles were rated level I and 57 articles were rated level II. The 15 level III articles were excluded. RESULTS: OCT angiography can detect decreased capillary vessel density within the peripapillary nerve fiber layer (level II) and macula (level I and II) in patients with suspected glaucoma, preperimetric glaucoma, and perimetric glaucoma. The degree of vessel density loss correlates significantly with glaucoma severity both overall and topographically (level II) as well as longitudinally (level I). For differentiating glaucomatous from healthy eyes, some studies found that peripapillary and macular vessel density measurements by OCTA show a diagnostic ability (area under the receiver operating characteristic curve) that is comparable with structural OCT retinal nerve fiber and ganglion cell thickness measurements, whereas other studies found that structural OCT measurements perform better. Choroidal or deep-layer microvasculature dropout as measured by OCTA is also associated with glaucoma damage (level I and II). Lower peripapillary and macular vessel density and choroidal microvasculature dropout are associated with faster rates of disease progression (level I and II). CONCLUSIONS: Vessel density loss associated with glaucoma can be detected by OCTA. Peripapillary, macular, and choroidal vessel density parameters may complement visual field and structural OCT measurements in the diagnosis of glaucoma.
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Xie L, Yin Y, Benowitz L. Chemokine CCL5 promotes robust optic nerve regeneration and mediates many of the effects of CNTF gene therapy. Proc Natl Acad Sci U S A 2021;118(9)Abstract
Ciliary neurotrophic factor (CNTF) is a leading therapeutic candidate for several ocular diseases and induces optic nerve regeneration in animal models. Paradoxically, however, although CNTF gene therapy promotes extensive regeneration, recombinant CNTF (rCNTF) has little effect. Because intraocular viral vectors induce inflammation, and because CNTF is an immune modulator, we investigated whether CNTF gene therapy acts indirectly through other immune mediators. The beneficial effects of CNTF gene therapy remained unchanged after deleting CNTF receptor alpha (CNTFRα) in retinal ganglion cells (RGCs), the projection neurons of the retina, but were diminished by depleting neutrophils or by genetically suppressing monocyte infiltration. CNTF gene therapy increased expression of C-C motif chemokine ligand 5 (CCL5) in immune cells and retinal glia, and recombinant CCL5 induced extensive axon regeneration. Conversely, CRISPR-mediated knockdown of the cognate receptor (CCR5) in RGCs or treating wild-type mice with a CCR5 antagonist repressed the effects of CNTF gene therapy. Thus, CCL5 is a previously unrecognized, potent activator of optic nerve regeneration and mediates many of the effects of CNTF gene therapy.
Xiong J, Yu C, Su T, Ge Q-M, Shi W-Q, Tang L-Y, Shu H-Y, Pan Y-C, Liang R-B, Li Q-Y, Shao Y. Altered brain network centrality in patients with mild cognitive impairment: an fMRI study using a voxel-wise degree centrality approach. Aging (Albany NY) 2021;13(11):15491-15500.Abstract
PURPOSE: Previous studies in patients with Alzheimer's disease have shown amyloid beta accumulation in the brain and abnormal brain activity, with mild cognitive impairment (MCI) in early stages of the disease. The aim of the current study was to investigate functional connectivity in patients with MCI. METHODS: We recruited 24 subjects in total, including 12 patients with MCI (6 men and 6 women) and 12 healthy controls (HCs) (6 men and 6 women), matched for age, gender, and lifestyle factors. All subjects underwent resting-state functional magnetic resonance imaging scans and voxel-wise degree centrality (DC) was used to evaluate alterations in the strength of brain network connectivity. RESULTS: The DC value of the left inferior temporal gyrus was lower in MCI but significantly higher in the right fusiform gyrus and the left supplementary motor area, compared with HCs. The DC value in left inferior temporal gyrus correlated positively with disease duration and negatively with Mini-Mental State Examination. ROC curve analysis of brain regions showed acceptable specificity and accuracy of DC values between MCIs and HCs in the area under the curve (right fusiform gyrus, 0.955; left supplementary motor area, 0.992; left inferior temporal gyrus, 1.000). CONCLUSIONS: Abnormal functional connectivity in brain regions of patients with MCI may reflect the pathological process of Alzheimer's disease development and could prove useful in clinical diagnosis and treatment.
Xu BY, Friedman DS, Foster PJ, Jiang Y, Pardeshi AA, Jiang Y, Munoz B, Aung T, He M. Anatomic Changes and Predictors of Angle Widening after Laser Peripheral Iridotomy: The Zhongshan Angle Closure Prevention Trial. Ophthalmology 2021;128(8):1161-1168.Abstract
PURPOSE: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy. DESIGN: Prospective observational study. PARTICIPANTS: Primary angle-closure suspects (PACSs) 50 to 70 years of age. METHODS: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o'clock) or temporal or nasal locations (at or below 10:30 or 1:30 o'clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 μm from the scleral spur (AOD750); poor angle widening, defined as the lowest quintile of change in mean AOD750; and poor angle opening, defined as residual PACS after LPI based on gonioscopy. MAIN OUTCOME MEASURES: Anatomic changes and predictors of angle widening and opening after LPI. RESULTS: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P < 0.006) after LPI, including greater AOD750 (P < 0.001). One hundred twenty eyes (26.4%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P = 0.004), smaller AOD750 (P < 0.001), and greater iris curvature (P < 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P < 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening. CONCLUSIONS: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI.
Xu BY, Friedman DS, Foster PJ, Jiang Y, Porporato N, Pardeshi AA, Jiang Y, Munoz B, Aung T, He M. Ocular Biometric Risk Factors for Progression of Primary Angle Closure Disease: The Zhongshan Angle Closure Prevention Trial. Ophthalmology 2021;Abstract
PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective observational study. PARTICIPANTS: 643 mainland Chinese aged 50 to 70 years with untreated PACS. METHODS: Participants received baseline clinical examinations including gonioscopy, anterior segment OCT (AS-OCT) imaging (Visante OCT, Carl Zeiss Meditec, Dublin, CA), and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. PACS was defined as inability to visualize pigmented trabecular meshwork in two or more quadrants based on static gonioscopy. PAC was defined as development of elevated intraocular pressure (IOP) > 24 mmHg or peripheral anterior synechiae (PAS). Progression was defined as development of PAC or an acute angle closure (AAC) attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Progression from PACS to PAC or AAC over 6 years. RESULTS: 643 untreated eyes (609 non-progressors, 34 progressors) of 643 ZAP participants were included in the primary analysis. In a multivariable model with continuous parameters, narrower horizontal angle opening distance 500 μm from the scleral spur (AOD500; OR=1.10 per 0.01 mm decrease, p=0.03), flatter horizontal iris curvature (IC; OR=1.96 per 0.1 mm decrease, p=0.01), and older age (OR=1.11 per year increase, p=0.01) at baseline were significantly associated with progression (AUC=0.73). Smaller cumulative gonioscopy score was not associated with progression (OR=1.03 per 1 modified Shaffer grade decrease; p=0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR=3.10, p=0.002) and IC (OR=2.48, p=0.014) measurements and aged 59 years and older (OR=2.68, p=0.01) at baseline had higher odds of progression (AUC=0.72). CONCLUSIONS: Ocular biometric measurements can help risk stratify patients with early angle closure for more severe disease. AS-OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not.
Xu J, Emmermann B, Bowers AR. Auditory Reminder Cues to Promote Proactive Scanning on Approach to Intersections in Drivers With Homonymous Hemianopia: Driving With Hemianopia, IX. JAMA Ophthalmol 2021;Abstract
Importance: Individuals with homonymous hemianopia (HH) are permitted to drive in some jurisdictions. They could compensate for their hemifield vision loss by scanning toward the blind side. However, some drivers with HH do not scan adequately well to the blind side when approaching an intersection, resulting in delayed responses to hazards. Objective: To evaluate whether auditory reminder cues promoted proactive scanning on approach to intersections. Design, Setting, and Participants: This cross-sectional, single-visit driving simulator study was conducted from October 2018 to May 2019 at a vision rehabilitation research laboratory. A volunteer sample of individuals with HH without visual neglect are included in this analysis. This post hoc analysis was completed in July and August 2020. Main Outcomes and Measures: Participants completed drives with and without scanning reminder cues (a single tone from a speaker on the blind side). Scanning was quantified by the percentage of intersections at which an early large scan was made (a scan with a head movement of at least 20° made before 30 m from the intersection). Responses to motorcycle hazards at intersections were quantified by the time to the first fixation and the time to the horn-press response. Results: Sixteen individuals were recruited and completed the study. Two were subsequently excluded from analyses. Thus, data from 14 participants (median [IQR] age, 54 [36-66] years; 13 men [93%]) were included. Stroke was the primary cause of the HH (10 participants [71%]). Six (43%) had right-sided HH. Participants were more likely to make an early large scan to the blind side in drives with vs without cues (65% vs 45%; difference, 20% [95% CI, 5%-37%]; P < .001). When participants made an early large scan to the blind side, they were faster to make their first fixation on blind-side motorcycles (mean [SD], 1.77 [1.34] vs 3.88 [1.17] seconds; difference, -2.11 [95% CI, -2.46 to -1.75] seconds; P < .001) and faster to press the horn (mean [SD], 2.54 [1.19] vs 4.54 [1.37] seconds; difference, -2.00 [95% CI, -2.38 to -1.62] seconds; P < .001) than when they did not make an early scan. Conclusions and Relevance: This post hoc analysis suggests that auditory reminder cues may promote proactive scanning, which may be associated with faster responses to hazards. This hypothesis should be considered in future prospective studies.
Xu C, Chen TC, Chodosh J, Eliott D, Mukai S, Shen LQ, Vavvas DG, Young LH, Lin MM. Endoscopic cyclophotocoagulation in Boston Keratoprosthesis Type II. Ophthalmol Glaucoma 2021;Abstract
This retrospective review of 7 cases demonstrates that endoscopic cyclophotocoagulation via eyelid incision and enlargement of pars plana vitrectomy entry sites can lower intraocular pressure in eyes with history of Boston keratoprosthesis Type II surgery.
Xue Y, Wang SK, Rana P, West ER, Hong CM, Feng H, Wu DM, Cepko CL. AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa. Elife 2021;10Abstract
Retinitis pigmentosa (RP) is an inherited retinal disease affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high-acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a disease gene-agnostic therapy, we screened 20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb) and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.
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Yan Y, Ludwig CA, Liao YJ. Multimodal Imaging Features of Optic Disc Drusen. Am J Ophthalmol 2021;Abstract
PURPOSE: Identify key en face multimodal imaging features of optic disc drusen (ODD). DESIGN: Retrospective cross-sectional study. METHODS: . SETTING: Single academic center. PATIENT OR STUDY POPULATION: 786 patients (age 10-82 years) with diagnostic codes for ODD or the term "optic disc drusen" in clinical notes extracted using natural language processing. INTERVENTION OR OBSERVATION PROCEDURES: Color fundus image, green-light and blue-light fundus autofluorescence (FAF), near-infrared reflectance (NIR), and enhanced-depth imaging optical coherence tomography (EDI-OCT). MAIN OUTCOME MEASURES: Ophthalmic imaging characteristics and sensitivity of en face imaging compared with EDI-OCT. RESULTS: 38 (61 eyes) of 786 patients had high-quality EDI-OCT and en face multimodal imaging. Green-light FAF had the highest sensitivity (96.8%) and showed homogeneously hyperautofluorescence while blue-light FAF differentiated superficial and deep ODD by the heterogeneous brightness of FAF. Blue-light FAF (93.5%) and NIR (91.8%) were also sensitive and provided important features including the location, size, and depth of ODD and morphology of the optic disc and ODD-associated features such as horizontal hyperreflective lines and peripapillary hyperreflective ovoid mass-like structures (PHOMS), respectively. Color fundus imaging had the lowest sensitivity (82%). There was good inter-rater reliability for all en face imaging modalities (P < .0001 for all). CONCLUSIONS: Green-light FAF had the highest sensitivity in diagnosis of ODD, while blue-light FAF and NIR provided more information regarding the severity, location, depth, and size of ODD. In eyes that are negative on green-light FAF, EDI-OCT can be performed and provides the highest-resolution characterization of the entire optic disc to rule out ODD.
Yang S, Kam WR, Liu Y, Ding J, Li Y, Sullivan DA. Comparative influence of differentiation and proliferation on gene expression in human meibomian gland epithelial cells. Exp Eye Res 2021;205:108452.Abstract
We recently discovered that by changing environmental signals, differentiated immortalized human meibomian gland epithelial cells (IHMGECs) de-differentiate into proliferating cells. We also discovered that following exposure to appropriate stimuli, these proliferative cells re-differentiate into differentiated IHMGECs. We hypothesize that this plasticity of differentiated and proliferative IHMGECs is paralleled by very significant alterations in cellular gene expression. To begin to test this hypothesis, we compared the gene expression patterns of IHMGECs during differentiation and proliferation. IHMGECs were cultured for four days in either differentiating or proliferating media. After four days of culture, cells were processed for the analysis of gene expression by using Illumina BeadChips and bioinformatic software. Our study identified significant differences in the expression of more than 9200 genes in differentiated and proliferative IHMGECs. Differentiation was associated with significant increases in the expression of specific genes (e.g. S100 calcium binding protein P; 7,194,386-fold upregulation) and numerous ontologies (e.g. 83 biological process [bp] ontologies with ≥100 genes were upregulated), such as those related to development, transport and lysosomes. Proliferation also led to a significant rise in specific gene expressions (e.g. cathelicidin antimicrobial peptide; 859,100-fold upregulation) and many ontologies (115 biological process [bp] ontologies with ≥100 genes were upregulated), with most of the highly significant ontologies related to cell cycle (z scores > 13.9). Our findings demonstrate that gene expression in differentiated and proliferative IHMGECs is extremely different. These results may have significant implications for the regeneration of HMGECs and the reversal of MG dropout in MG dysfunction.
Yang S-A, Mitchell W, Hall N, Elze T, Lorch AC, Miller JW, Zebardast N, Zebardast N. Trends and Usage Patterns of Minimally Invasive Glaucoma Surgery in the United States: IRIS® Registry Analysis 2013-2018. Ophthalmol Glaucoma 2021;4(6):558-568.Abstract
PURPOSE: Understanding trends and patterns in the use of minimally invasive glaucoma surgery (MIGS) and patient profiles undergoing each procedure is important given their relative expense and unknown long-term safety and effectiveness. DESIGN: Retrospective analysis. PARTICIPANTS: Minimally invasive glaucoma surgeries and standard glaucoma surgeries recorded in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. METHODS: We used the data from IRIS Registry between 2013 and 2018 (inclusive) to measure the annual number of MIGS and standard surgical techniques (trabeculectomy or glaucoma drainage device [GDD] placement) performed in the United States, stratified by demographic characteristics. Secondary analyses of concurrent surgeries and of subsequent surgeries for MIGS and standard surgical technique also were conducted. MAIN OUTCOME MEASURES: Trends and sociodemographic characteristics of MIGS use in the United States. RESULTS: Two hundred three thousand three hundred thirty-two eyes and 232 537 unique procedures had associated, documented International Statistical Classification of Diseases and Related Health Problems (ICD), Ninth or Tenth Revision, codes for glaucoma and were included in final analyses. Among eyes with documented glaucoma diagnoses, a substantial increase in annual MIGS procedures occurred over the study period (from 7586 in 2013 to 39 677) and a smaller decrease in standard glaucoma procedures (from 16 215 to 13 701). The proportion of iStent procedures almost tripled during the study period (from 14% to 40%), and by 2017 accounted for almost half (43.7%) of all glaucoma surgeries in the United States. Twenty-one thousand twenty-five of all eyes (10.3%) underwent multiple procedures: 7638 (36.3%) on the same day and 13 387 (63.7%) on subsequent days. Endocyclophotocoagulation and iStent placement were the most common concurrent procedures (55.4% of all concurrent procedures). Trabeculectomy and GDD placement were most commonly followed by another standard glaucoma surgery, but when followed by sequential MIGS, endocyclophotocoagulation and goniotomy were the most common procedures performed (33.0% and 21.9%, respectively). CONCLUSIONS: A significant increase in MIGS use occurred over the recent 6-year period, despite limited evidence of their long-term safety or effectiveness, highlighting the need for trials comparing safety and outcomes of novel MIGS versus traditional surgical treatments for glaucoma.
Yang S-A, Mitchell WG, Hall N, Elze T, Miller JW, Lorch AC, Zebardast N. Usage Patterns of Minimally Invasive Glaucoma Surgery (MIGS) Differ by Glaucoma Type: IRIS Registry Analysis 2013-2018. Ophthalmic Epidemiol 2021;:1-9.Abstract
Purpose: To examine patterns of standard (trabeculectomy or glaucoma drainage devices, GDDs) vs novel (minimally invasive glaucoma surgery, MIGS) surgical techniques in the US.Methods: We used the American Academy of Ophthalmology (AAO) IRIS® Registry (Intelligent Research in Sight) queried between 2013 and 2018 (inclusive) to calculate the cumulative proportion of stand-alone, concurrent (same day) or sequential (subsequent day) glaucoma surgical techniques performed in each glaucoma diagnosis type. Secondary analyses of adjusted proportions of concurrent and sequential surgeries stratified by glaucoma diagnosis were also performed.Results: Of 203,146 eyes receiving glaucoma surgeries, open angle glaucoma (OAG) was most likely to undergo all types of intervention. The iStent was the most commonly performed MIGS, primarily for those with normal tension glaucoma (NTG) or OAG (p < .001). Conversely, GDD was the most commonly performed procedure in secondary glaucoma or other (specified) glaucoma (p < .001). ECP and iStent were the most common concurrent procedures performed; most often for OAG and NTG (p < .001). After an initial standard surgery, most eyes underwent recurrent standard interventions (90.3%). ECP was the most common MIGS performed after an initial standard surgery; particularly in primary angle-closure (PACG) and secondary glaucoma eyes (p < .001).Conclusion: Glaucoma type may influence the choice of glaucoma procedures and the decision to perform concurrent as well sequential surgical procedures. Given the poorly understood long term safety and effectiveness of MIGS, and with substantially increasing use of MIGS procedures in recent years, future studies comparing their safety and effectiveness vs standard interventions, for a variety of glaucoma types, is needed.
Yannuzzi NA, Watane A, Patel NA, Townsend JH. Haptic and Haptic-Optic Junction Structural Integrity of CT Lucia and MA60 Intraocular Lenses. J Cataract Refract Surg 2021;
Yemanyi F, Bora K, Blomfield AK, Wang Z, Chen J. Wnt Signaling in Inner Blood-Retinal Barrier Maintenance. Int J Mol Sci 2021;22(21)Abstract
The retina is a light-sensing ocular tissue that sends information to the brain to enable vision. The blood-retinal barrier (BRB) contributes to maintaining homeostasis in the retinal microenvironment by selectively regulating flux of molecules between systemic circulation and the retina. Maintaining such physiological balance is fundamental to visual function by facilitating the delivery of nutrients and oxygen and for protection from blood-borne toxins. The inner BRB (iBRB), composed mostly of inner retinal vasculature, controls substance exchange mainly via transportation processes between (paracellular) and through (transcellular) the retinal microvascular endothelium. Disruption of iBRB, characterized by retinal edema, is observed in many eye diseases and disturbs the physiological quiescence in the retina's extracellular space, resulting in vision loss. Consequently, understanding the mechanisms of iBRB formation, maintenance, and breakdown is pivotal to discovering potential targets to restore function to compromised physiological barriers. These unraveled targets can also inform potential drug delivery strategies across the BRB and the blood-brain barrier into retinas and brain tissues, respectively. This review summarizes mechanistic insights into the development and maintenance of iBRB in health and disease, with a specific focus on the Wnt signaling pathway and its regulatory role in both paracellular and transcellular transport across the retinal vascular endothelium.
Yeung V, Sriram S, Tran JA, Guo X, Hutcheon AEK, Zieske JD, Karamichos D, Ciolino JB. FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro. Biomolecules 2021;11(11)Abstract
Corneal fibrosis (or scarring) occurs in response to ocular trauma or infection, and by reducing corneal transparency, it can lead to visual impairment and blindness. Studies highlight important roles for transforming growth factor (TGF)-β1 and -β3 as modulators in corneal wound healing and fibrosis, leading to increased extracellular matrix (ECM) components and expression of α-smooth muscle actin (αSMA), a myofibroblast marker. In this study, human corneal fibroblasts (hCF) were cultured as a monolayer culture (2D) or on poly-transwell membranes to generate corneal stromal constructs (3D) that were treated with TGF-β1, TGF-β3, or TGF-β1 + FAK inhibitor (FAKi). Results show that hCF 3D constructs treated with TGF-β1 or TGF-β3 impart distinct effects on genes involved in wound healing and fibrosis-ITGAV, ITGB1, SRC and ACTA2. Notably, in the 3D construct model, TGF-β1 enhanced αSMA and focal adhesion kinase (FAK) protein expression, whereas TGF-β3 did not. In addition, in both the hCF 2D cell and 3D construct models, we found that TGF-β1 + FAKi attenuated TGF-β1-mediated myofibroblast differentiation, as shown by abrogated αSMA expression. This study concludes that FAK signaling is important for the onset of TGF-β1-mediated myofibroblast differentiation, and FAK inhibition may provide a novel beneficial therapeutic avenue to reduce corneal scarring.
Yin J. Advances in corneal graft rejection. Curr Opin Ophthalmol 2021;32(4):331-337.Abstract
PURPOSE OF REVIEW: Immune rejection after corneal transplantation is a major risk for graft failure. We aim to summarize recent advances in the understanding and management of graft rejection. RECENT FINDINGS: Immune rejection remains the leading cause of graft failure in penetrating keratoplasty (PKP). While ABO blood type and sex match between donor and recipient may reduce rejection, human leucocyte antigens class II matching in a randomized study did not reduce the risk of rejection in high-risk PKP. Compared with PKP, deep anterior lamellar keratoplasty, descemet stripping automated endothelial keratoplasty, and descemet membrane endothelial keratoplasty have lower immune rejection rates of 1.7-13%, 5-11.4%, and 1.7-2.8%, respectively, based on long-term (5 years and more) studies. Whether immune rejection is a major risk factor for graft failure in these lamellar keratoplasties is unclear. While there have not been major advances in the systemic management of graft rejection, topical nonsteroid agents such as tacrolimus and anti-vascular endothelial growth factor have shown promise in high-risk cases. SUMMARY: Immune rejection remains the leading cause of graft failure in PKP. Lamellar keratoplasties have significantly lower rejection rates compared with PKP. The significance of rejection in the failure of lamellar grafts warrants further investigation.
Yoon MK, Kelly HR, Freitag SK, Marneros AG, Barshak MB, Brackett DG. Case 12-2021: A 78-Year-Old Man with a Rash on the Scalp and Face. N Engl J Med 2021;384(16):1553-1562.
Yoon MK, Habib LA. Spheno-Orbital Dermoid Masquerading as Recurrent Orbital Abscess. Ophthalmic Plast Reconstr Surg 2021;37(6):e213-e215.Abstract
A 10-month-old girl presented with eyelid edema and erythema that did not improve with systemic antibiotics. Due to a lack of improvement, MRI was performed to avoid ionizing radiation from CT. An orbital abscess was recognized and drained. However, the abscess recurred 2 times. CT scan was performed and a tract in the sphenoid bone helped to diagnose a congenital dural sinus tract with dermoid. Definitive surgery was performed with neurosurgery to remove the entire tract including cutaneous connection. CT scan proved critical to diagnosis and should be considered in infants in select cases despite the concern for ionizing radiation in this vulnerable age group.
Yu K, Guo Y, Ge Q-M, Su T, Shi W-Q, Zhang L-J, Shu H-Y, Pan Y-C, Liang R-B, Li Q-Y, Shao Y. Author Correction: Altered spontaneous activity in the frontal gyrus in dry eye: a resting-state functional MRI study. Sci Rep 2021;11(1):17653.

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