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Costela FM, Reeves SM, Woods RL. The Effect of Zoom Magnification and Large Display on Video Comprehension in Individuals With Central Vision Loss. Transl Vis Sci Technol 2021;10(8):30.Abstract
Purpose: A larger display at the same viewing distance provides relative-size magnification for individuals with central vision loss (CVL). However, the resulting large visible area of the display is expected to result in more head rotation, which may cause discomfort. We created a zoom magnification technique that placed the center of interest (COI) in the center of the display to reduce the need for head rotation. Methods: In a 2 × 2 within-subject study design, 23 participants with CVL viewed video clips from 1.5 m (4.9 feet) shown with or without zoom magnification, and with a large (208 cm/82" diagonal, 69°) or a typical (84 cm/33", 31°) screen. Head position was tracked and a custom questionnaire was used to measure discomfort. Results: Video comprehension was better with the large screen (P < 0.001) and slightly worse with zoom magnification (P = 0.03). Oddly, head movements did not vary with screen size (P = 0.63), yet were greater with zoom magnification (P = 0.001). This finding was unexpected, because the COI remains in the center with zoom magnification, but moves widely with a large screen and no magnification. Conclusions: This initial attempt to implement the zoom magnification method had flaws that may have decreased its effectiveness. In the future, we propose alternative implementations for zoom magnification, such as variable magnification. Translational Relevance: We present the first explicit demonstration that relative-size magnification improves the video comprehension of people with CVL when viewing video.
Bosque LE, Yamarino CR, Salcedo N, Schneier AJ, Gold RS, Blumenfeld LC, Hunter DG. Evaluation of the blinq vision scanner for detection of amblyopia and strabismus. J AAPOS 2021;Abstract
PURPOSE: To report the results of a clinical study designed to evaluate the accuracy of the blinq pediatric vision scanner, which detects amblyopia and strabismus directly by means of retinal polarization scanning, unlike other vision screening devices, which infer possible disease based on detection of refractive risk factors. METHODS: Subjects 1-20 years of age were prospectively enrolled in this cross-sectional diagnostic accuracy study with planned enrollment of 200. All enrolled subjects were tested by individuals masked to the diagnosis, followed by complete ophthalmologic examination by pediatric ophthalmologists masked to the screening result. Patients previously treated for amblyopia or strabismus were analyzed separately. RESULTS: The study cohort comprised 193 subjects, 53 of whom had been previously treated, leaving 140 treatment-naïve subjects, including 65 (46%) with amblyopia or strabismus, 11 (8%) with risk factors/suspected binocular vision deficit without amblyopia/strabismus, and 64 (46%) controls. Sensitivity was 100%, with all 66 patients with referral-warranted ocular disease referred. Five patients with intermittent strabismus receiving pass results were deemed "acceptable pass" when considering patient risk factors and amblyogenic potential. Specificity was 91%, with 7 incorrect referrals. Subanalysis of children aged 2-8 years (n = 92) provided similar results (sensitivity 100%; specificity 89%). CONCLUSIONS: In this study cohort, the blinq showed very high sensitivity and specificity for detecting referral-warranted amblyopia and strabismus. Implementation of the device in vision screening programs could lead to improved rates of disease detection and reduction in false referrals.
McCoskey M, Neerukonda VK, Hatton MP, Wolkow N. Eccrine poroma of the eyelid. Orbit 2021;:1.Abstract
Clinical and histopathologic case of an eyelid eccrine poroma, a benign adnexal neoplasm rarely found on the periorbital skin.
Song A, Deshmukh R, Lin H, Ang M, Mehta JS, Chodosh J, Said DG, Dua HS, Ting DSJ. Post-keratoplasty Infectious Keratitis: Epidemiology, Risk Factors, Management, and Outcomes. Front Med (Lausanne) 2021;8:707242.Abstract
Post-keratoplasty infectious keratitis (PKIK) represents a unique clinical entity that often poses significant diagnostic and therapeutic challenges. It carries a high risk of serious complications such as graft rejection and failure, and less commonly endophthalmitis. Topical corticosteroids are often required to reduce the risk of graft rejection but their use in PKIK may act as a double-edged sword, particularly in fungal infection. The increased uptake in lamellar keratoplasty in the recent years has also led to complications such as graft-host interface infectious keratitis (IIK), which is particularly difficult to manage. The reported incidence of PKIK differs considerably across different countries, with a higher incidence observed in developing countries (9.2-11.9%) than developed countries (0.02-7.9%). Common risk factors for PKIK include the use of topical corticosteroids, suture-related problems, ocular surface diseases and previous corneal infection. PKIK after penetrating keratoplasty or (deep) anterior lamellar keratoplasty is most commonly caused by ocular surface commensals, particularly Gramme-positive bacteria, whereas PKIK after endothelial keratoplasty is usually caused by Candida spp. Empirical broad-spectrum antimicrobial treatment is the mainstay of treatment for both PKIK, though surgical interventions are required in medically refractory cases (during the acute phase) and those affected by visually significant scarring (during the late phase). In this paper, we aim to provide a comprehensive overview on PKIK, encompassing the epidemiology, risk factors, causes, management and outcomes, and to propose a treatment algorithm for systematically managing this challenging condition.
Birnbaum FA, Neeson C, Solá-Del Valle D. Microinvasive Glaucoma Surgery: An Evidence-Based Review. Semin Ophthalmol 2021;36(8):772-786.Abstract
PURPOSE: Interest in micro-invasive glaucoma surgery (MIGS) has exploded over the last 8 years with an increase in MIGS procedures of at least 400% in the United States, according to Medicare data. MIGS is an umbrella term that can cover many different types of surgeries. This review focuses on peer-reviewed evidence for Trabectome®, iStent inject®, Kahook Dual Blade®, XEN® Gel Stent, and Hydrus®. METHODS: We present key recent studies evaluating the efficacy and safety of MIGS in various types of glaucoma patients with different stages of disease. CONCLUSION: We conclude that MIGS is generally safe and efficacious, although only some MIGS have been studied through randomized clinical trials. When comparing and contrasting the different MIGS procedures, large prospective studies are not yet the norm. High-quality large prospective studies involving MIGS will be an important next step as ophthalmologists decide how to incorporate MIGS into their surgical armamentarium.
Gram M, Ekström C, Holmqvist B, Carey G, Wang X, Vallius S, Hellström W, Ortenlöf N, Agyemang AA, Smith LEH, Hellström A, Mangili A, Barton N, Ley D. Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3. Dev Neurosci 2021;:1-15.Abstract
Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.
Hibert ML, Chen Y, Ohringer N, Feuer WJ, Waheed NK, Heier JS, Calhoun MW, Rosenfeld PJ, Polimeni JR. Altered Blood Flow in the Ophthalmic and Internal Carotid Arteries in Patients with Age-Related Macular Degeneration Measured Using Noncontrast MR Angiography at 7T. AJNR Am J Neuroradiol 2021;Abstract
BACKGROUND AND PURPOSE: Age-related macular degeneration is associated with reduced perfusion of the eye; however, the role of altered blood flow in the upstream ophthalmic or internal carotid arteries is unclear. We used ultra-high-field MR imaging to investigate whether the diameter of and blood flow in the ophthalmic artery and/or the ICA are altered in age-related macular degeneration and whether any blood flow changes are associated with disease progression. MATERIALS AND METHODS: Twenty-four patients with age-related macular degeneration and 13 similarly-aged healthy controls participated. TOF and high-resolution dynamic 2D phase-contrast MRA (0.26 × 0.26 × 2mm3, 100-ms effective sampling rate) was acquired at 7T. Vessel diameters were calculated from cross-sectional areas in phase-contrast acquisitions. Blood flow time-series were measured across the cardiac cycle. RESULTS: The ophthalmic artery vessel diameter was found to be significantly smaller in patients with age-related macular degeneration than in controls. Volumetric flow through the ophthalmic artery was significantly lower in patients with late age-related macular degeneration, with a significant trend of decreasing volumetric ophthalmic artery flow rates with increasing disease severity. The resistance index was significantly greater in patients with age-related macular degeneration than in controls in the ophthalmic artery. Flow velocity through the ophthalmic artery and ICA was significantly higher in patients with age-related macular degeneration. Ophthalmic artery blood flow as a percentage of ipsilateral ICA blood flow was nearly double in controls than in patients with age-related macular degeneration. CONCLUSIONS: These findings support the hypothesis that vascular changes upstream to the eye are associated with the severity of age-related macular degeneration. Additional investigation into the potential causality of this relationship and whether treatments that improve ocular circulation slow disease progression is warranted.
Lee SJ, Kim S-T, Wu J, Cho CS, Jo DH, Chen Y, Dana R, Kim JH, Lee S-M. Corneal lymphangiogenesis in dry eye disease is regulated by substance P/neurokinin-1 receptor system through controlling expression of vascular endothelial growth factor receptor 3. Ocul Surf 2021;22:72-79.Abstract
PURPOSE: To evaluate the role of substance P (SP)/neurokinin-1 receptor (NK1R) system in the regulation of pathologic corneal lymphangiogenesis in dry eye disease (DED). METHODS: Immunocytochemistry, angiogenesis assay, and Western blot analysis of human dermal lymphatic endothelial cells (HDLECs) were conducted to assess the involvement of SP/NK1R system in lymphangiogenesis. DED was induced in wild-type C57BL/6 J mice using controlled-environment chamber without scopolamine. Immunohistochemistry, corneal fluorescein staining, and phenol red thread test were used to evaluate the effect of SP signaling blockade in the corneal lymphangiogenesis. The expression of lymphangiogenic factors in the corneal and conjunctival tissues of DED mouse model was quantified by real-time polymerase chain reaction. RESULTS: NK1R expression and pro-lymphangiogenic property of SP/NK1R system in HDLECs were confirmed by Western blot analysis and angiogenesis assay. Blockade of SP signaling with L733,060, an antagonist of NK1R, or NK1R-targeted siRNA significantly inhibited lymphangiogenesis and expression of vascular endothelial growth factor (VEGF) receptor 3 stimulated by SP in HDLECs. NK1R antagonist also suppressed pathological corneal lymphangiogenesis and ameliorated the clinical signs of dry eye in vivo. Furthermore, NK1R antagonist effectively suppressed the lymphangiogenic factors, including VEGF-C, VEGF-D, and VEGF receptor 3 in the corneal and conjunctival tissues of DED. CONCLUSIONS: SP/NK1R system promotes lymphangiogenesis in vitro and NK1R antagonism suppresses pathologic corneal lymphangiogenesis in DED in vivo.
Charles NC, Stagner AM, Raju LV, Belinsky I. Conjunctival Exophytic Schneiderian-type Papillomas: A Rare Occurrence. Ophthalmic Plast Reconstr Surg 2021;Abstract
Conjunctival papillomas are common tumors that exhibit an exophytic growth pattern, comprised of multiple filiform fronds of squamous epithelium that contain fibrovascular cores. The inverted (endophytic) variety of papilloma, often termed "Schneiderian," rarely occurs on the conjunctiva, with only 15 cases reported to date. Endophytic and exophytic papillomas are well described arising in the sinonasal Schneiderian epithelium where a low rate of malignant transformation may occur in the endophytic type; malignant transformation in exophytic sinonasal papillomas is exceedingly rare. The authors describe 2 cases of exophytic conjunctival papillomas with the morphology of a sinonasal or Schneiderian-type papilloma. Both were pink, sessile acquired growths in women in the sixth decade of life involving the inferior conjunctival fornix or nasal limbus. Nonkeratinizing squamous epithelium along with numerous goblet cells, intraepithelial mucinous cysts, and microabscesses were present. Immunohistochemistry showed reactivity for cytokeratin 7 and wild-type staining for p16 and p53, paralleling the findings in common conjunctival papillomas; both were also driven by low-risk human papillomavirus.
Starr CE, Dana R, Pflugfelder SC, Holland EJ, Zhang S, Owen D, Brazzell K. Dry eye disease flares: A rapid evidence assessment. Ocul Surf 2021;22:51-59.Abstract
PURPOSE: Characteristics of periodic flares of dry eye disease (DED) are not well understood. We conducted a rapid evidence assessment to identify evidence for and characteristics of DED flares. METHODS: Literature searches were performed in Embase® via Ovid®, MEDLINE®, and PubMed®. Clinical trials and observational studies published 2009-2019 were included if they investigated patients aged ≥18 years with clinically diagnosed DED who experienced a flare, defined as a temporary or transient episode of increased ocular discomfort, typically lasting days to a few weeks. Triggers of flares, patient-reported outcomes (symptoms), clinician-measured outcomes (signs), and changes in tear molecules were captured. RESULTS: Twenty-one publications that included 22 studies met inclusion criteria. Five observational studies described evidence of DED flares in daily life, 5 studies reported changes following cataract/refractive surgery in patients with preoperative DED, and 12 studies employed controlled environment (CE) models. Real-world triggers of DED flares included air conditioning, wind, reading, low humidity, watching television, and pollution. CE chambers (dry, moving air) and surgery also triggered DED flares. Exacerbations of symptoms and signs of DED, assessed through varied measures, were reported during flares. Across studies, matrix metalloproteinase-9 and interleukin-6 increased and epidermal growth factor decreased during DED flares. CONCLUSIONS: Evidence from 22 studies identified triggers and characteristics of DED flares. Further research is needed to assist clinicians in early diagnosis and treatment of patients experiencing flares.
Mychaleckyj J, Valo E, Ichimura T, Ahluwalia T, Dina C, Miller R, Shabalin I, Gyorgy B, Cao J, Onengut-Gumuscu S, Satake E, Smiles A, Haukka J, Tregouet D-A, Costacou T, O'Neil K, Paterson A, Forsblom C, Keenan H, Pezzolesi M, Pragnell M, Galecki A, Rich S, Sandholm N, Klein R, Klein B, Susztak K, Orchard T, Korstanje R, King G, Hadjadj S, Rossing P, Bonventre J, Groop P-H, Warram J, Krolewski A. Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes. J Am Soc Nephrol 2021;Abstract
BACKGROUND: Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of end stage kidney disease (ESKD) in individuals with type 1 diabetes at advanced kidney disease stage. METHODS: Gene-based exome array analysis of 15,449 genes in 5 large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time-to-ESKD, testing the top gene in a 6th cohort (N=2,372/1,115 events all cohorts) and replicating in two retrospective case-control studies (N=1,072 cases, 752 controls). Deep resequencing of the top associated gene in 5 cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models. RESULTS: Protein coding variants in the hydroxysteroid 17-beta dehydrogenase 14 gene (HSD17B14), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance (N=4,196; p-value=3.3x10-7). The HSD17B14 gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed HSD17B14 gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other chronic kidney disease-associated renal pathologies. CONCLUSIONS: HSD17B14 gene is mechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.
Rashad R, Shanbhag SS, Kwan J, Chodosh J, Saeed S, Saeed HN. Chronic ocular complications in lamotrigine vs. trimethoprim-sulfamethoxazole induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf 2021;21:16-18.Abstract
PURPOSE: The purpose of this study is to compare the severity of chronic ocular complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by lamotrigine (LT) vs. trimethoprim-sulfamethoxazole (TS). METHODS: This retrospective cross-sectional study evaluated all SJS/TEN patients treated within our hospital network from 2008 to 2018. Inclusion criteria included patients with reactions identified as caused by either LT or TS, and patients with at least one ophthalmology follow up in the chronic phase (≥3 months from disease onset). Primary outcome measures included LogMAR best-corrected VA at most recent visit and the presence or absence of severe ocular complications (SOC). Secondary outcome measures included chronic ocular complication severity scores using a modified Sotozono scoring system. RESULTS: Forty-eight eyes of 24 patients were included in the study. The mean duration of follow-up was 39.50 ± 35.62 vs. 48.17 ± 33.09 months, respectively (p = 0.482). The LT group had worse average VA at the most recent visit (LogMAR VA; 0.508 vs. 0.041, p < 0.0001) and had a higher prevalence of SOCs (66.7% vs. 8.3%, p = 0.0038). The LT group scored worse on Sotozono chronic complications scores for the cornea (1.875 vs. 0.5, p = 0.0018), eyelid margin (5.583 vs.3.083, p = 0.0010), and overall condition (8.500 vs. 4.833, p = 0.0015). Sub-analyses showed that a moderate or severe acute ocular severity score was a significant predictor of chronic outcomes. CONCLUSIONS: Compared to patients with TS-induced SJS/TEN, patients with LT-induced SJS/TEN developed worse chronic ocular complications on several parameters. Future prospective studies are warranted to provide additional insight into the drug type as a predictor of chronic ocular complications.
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.
Soeken TA, Ross AE, Kohane DS, Kuang L, Legault GL, Caldwell MC, Brundridge WL, Merkley MB, Ciolino JB, Townley RJ. Dexamethasone-Eluting Contact Lens for the Prevention of Postphotorefractive Keratectomy Scar in a New Zealand White Rabbit Model. Cornea 2021;40(9):1175-1180.Abstract
PURPOSE: To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model. METHODS: Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.1% dexamethasone ophthalmic solution (drops) for 4 weeks, tarsorrhaphy and BCL replaced weekly plus topical dexamethasone for 4 weeks, and tarsorrhaphy and DCL changed weekly for 4 weeks. Each week for 4 consecutive weeks postoperatively, the tarsorrhaphies were opened, the eyes underwent evaluation and imaging, and the tarsorrhaphies were replaced. Contact lenses were cultured on removal. Central corneal haze was assessed weekly with corneal densitometry. After 4 weeks, the animals were killed, and the eyes were enucleated for histopathologic analysis. RESULTS: The tarsorrhaphy only group displayed more haze with a greater change in optical densitometry from pre-op compared with the other treatment groups. There was no difference between the DCL group and the groups receiving a BCL and dexamethasone drops in densitometry or histopathology. No NZW rabbits developed clinical signs of infection, and cultures from DCLs and BCLs grew similar organisms. CONCLUSIONS: In the post-PRK rabbit model, DCLs worn weekly for 4 weeks were safe and as effective at preventing corneal haze as 0.1% dexamethasone drops applied 4 times a day for 4 weeks.

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