June 2020

Corneal dystrophies are broadly defined as inherited disorders that affect any layer of the cornea and are usually progressive, bilateral conditions that do not have systemic effects. The 2015 International Classification of Corneal Dystrophies classifies corneal dystrophies into four classes: epithelial and subepithelial dystrophies, epithelial-stromal TGFBI dystrophies, stromal dystrophies and endothelial dystrophies. Whereas some corneal dystrophies may result in few or mild symptoms and morbidity throughout a patient's lifetime, others may progress and eventually result in substantial visual and ocular disturbances that require medical or surgical intervention. Corneal transplantation, either with full-thickness or partial-thickness donor tissue, may be indicated for patients with advanced corneal dystrophies. Although corneal transplantation techniques have improved considerably over the past two decades, these surgeries are still associated with postoperative risks of disease recurrence, graft failure and other complications that may result in blindness. In addition, a global shortage of cadaveric corneal graft tissue critically limits accessibility to corneal transplantation in some parts of the world. Ongoing advances in gene therapy, regenerative therapy and cell augmentation therapy may eventually result in the development of alternative, novel treatments for corneal dystrophies, which may substantially improve the quality of life of patients with these disorders.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.

Objective: To investigate the incidence, clinicopathological characteristics and survival of ocular adnexal lymphoma (OAL) in the paediatric population. Methods and analysis: In this retrospective case series, the Surveillance, Epidemiology and End Results database was accessed to identify individuals with OAL ≤18 years of age, diagnosed between 1973 and 2015. OAL located in the eyelid, conjunctiva, lacrimal apparatus and orbit were included. Main outcome measures were the age-adjusted incidence rates (IRs) per 1 000 000 population at risk (calculated for the period 2000-2015) and descriptive statistics of demographic and clinicopathological features. Results: The IR of paediatric OAL was 0.12 (95% CI 0.08 to 0.16) per 1 000 000. Males (0.15; 95% CI 0.10 to 0.22) and blacks (0.24; 95% CI 0.13 to 0.42) had a higher tendency for OAL development. A total of 55 tumours in 54 children were identified. The majority were localised (78.4%), conjunctival (49.1%) lymphomas. Extranodal marginal zone lymphoma (EMZL, 45.5%, n=25) was the most frequent subtype, followed by diffuse large B-cell lymphoma (DLBCL, 9.1%, n=5), B lymphoblastic lymphoma (7.3%, n=4), follicular lymphoma (5.5%, n=3), Burkitt lymphoma (5.5%, n=3), anaplastic large cell lymphoma (ALCL, 3.6%, n=2), small lymphocytic lymphoma (1.8%, n=1), diffuse large B-cell lymphoma, immunoblastic (1.8%, n=1) and panniculitis-like T-cell lymphoma (1.8%, n=1). Localised, low-grade, conjunctival lymphomas were frequently treated with complete excision with or without radiation, while high-grade and distant tumours usually received chemotherapy. Only 29.1% of paediatric OAL cases were treated with radiation. Three out of five (60%) patients with DLBCL died of lymphoma at a median follow-up of 21 (range 10-86) months, and 1 out of 2 (50%) patients with ALCL died of lymphoma at 23 months from diagnosis. Conclusion: OAL in the paediatric population is rare. The majority of OAL are EMZL and are characterised by excellent prognosis. The histological subtype was found to be the main predictor of outcome with cancer-specific deaths observed in patients with DLBCL and ALCL.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

PURPOSE: Current sequencing strategies can genetically solve 55-60% of inherited retinal degeneration (IRD) cases, despite recent progress in sequencing. This can partially be attributed to elusive pathogenic variants (PVs) in known IRD genes, including copy-number variations (CNVs), which have been shown as major contributors to unsolved IRD cases. METHODS: Five hundred IRD patients were analyzed with targeted next-generation sequencing (NGS). The NGS data were used to detect CNVs with ExomeDepth and gCNV and the results were compared with CNV detection with a single-nucleotide polymorphism (SNP) array. Likely causal CNV predictions were validated by quantitative polymerase chain reaction (qPCR). RESULTS: Likely disease-causing single-nucleotide variants (SNVs) and small indels were found in 55.6% of subjects. PVs in USH2A (11.6%), RPGR (4%), and EYS (4%) were the most common. Likely causal CNVs were found in an additional 8.8% of patients. Of the three CNV detection methods, gCNV showed the highest accuracy. Approximately 30% of unsolved subjects had a single likely PV in a recessive IRD gene. CONCLUSION: CNV detection using NGS-based algorithms is a reliable method that greatly increases the genetic diagnostic rate of IRDs. Experimentally validating CNVs helps estimate the rate at which IRDs might be solved by a CNV plus a more elusive variant.

: To examine factors decreasing participation in school-based vision programs from parent and teacher perspectives.: We conducted 41 semi-structured focus groups (20 parent groups, 21 teacher/staff groups), at 10 Baltimore and 11 Chicago public elementary and middle schools offering school-based vision programs. School-based vision programs provided vision screening, eye exams, and eyeglasses if needed. Focus groups ranged in size from 2-9 participants (median = 5). Sessions were recorded, transcribed, and coded through an iterative process to develop themes using inductive analysis.: Ninety parents and 117 teachers/staff participated. Participants identified five major factors decreasing participation in school-based vision programs: (1) challenges with the consent form, including distribution, collection, and literacy and language barriers; (2) having existing eye care; (3) misunderstandings about the program, especially related to cost and insurance; (4) difficulty raising parental awareness of the program; and (5) certain attitudes towards vision, eye care, and school-based programs, including low prioritization of eye care, mistrust of the program, fear of sharing private information, not believing their child needs glasses, and reluctance accepting 'subsidized' services.: Parents and teachers identified important structural barriers to participation (i.e., consent form challenges and low parental awareness) and specific reasons for non-participation (i.e., attitudes, misunderstanding of the program, existing eye care) in school-based vision programs. Effective strategies are needed to facilitate return of consent forms and promote awareness of school-based vision programs among parents. Programs should also target services towards those currently without access to eye care and increase awareness about paediatric vision needs.

PURPOSE: To quantitatively analyze the angle anatomy in eyes with a Boston type 1 keratoprosthesis (KPro) using anterior segment optical coherence tomography (AS-OCT) and to assess the diagnostic ability of AS-OCT in KPro-associated glaucoma. METHODS: AS-OCT (RTVue) images from KPro eyes with and without glaucoma were reviewed. The angle opening distance at 500 μm from the scleral spur (AOD500), trabecular-iris angle at 500 μm from the scleral spur (TIA500), and trabecular-iris surface area at 500 μm from the scleral spur (TISA500) were measured by 2 observers masked to the diagnosis. The measurements for each visible quadrant were compared between KPro eyes with and without glaucoma. RESULTS: Twenty-two eyes with glaucoma and 17 eyes without glaucoma from 39 patients with KPro were included. Of the 4 quadrants imaged, the temporal angle was the most visible (79.5%) and angle measurements of the temporal quadrant were the only ones that differentiated the 2 groups: the mean AOD500, TIA500, and TISA500 were significantly lower in KPro eyes with glaucoma than without glaucoma (388.2 ± 234.4 μm vs. 624.5 ± 310.5 μm, P = 0.02; 26.1 ± 14.0 degrees vs. 39.1 ± 17.1 degrees, P = 0.03; and 0.15 ± 0.09 mm vs. 0.23 ± 0.12 mm, P = 0.03; respectively). The highest area under the receiver operating characteristic curve for detecting glaucoma was 0.75 for temporal TIA500 (95% confidence interval 0.57-0.94, P = 0.02) with 50% specificity at 80% of sensitivity and a cutoff value of 37 degrees. CONCLUSIONS: The temporal angle was the most visible on AS-OCT in eyes with a KPro. Significant narrowing of the temporal angle detected on AS-OCT was associated with glaucoma in these eyes.

BACKGROUND/AIMS: Although being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy. METHODS: Cross-sectional study. A total of 2027 phakic subjects aged ≥50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of ≥35%, ≥50% and ≥75% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT. RESULTS: Two hundred and seventy-two (14.7%) resulted in overcall results (false positives) when ≥50% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, p<0.001) and deeper (anterior chamber depth (ACD), 2.4 vs 2.2 mm, p<0.001) anterior chambers than eyes assessed by both methods as closed (true positives). Deeper ACD (OR 9.31) and lower lens vault (LV) (OR 0.04) were significantly associated with a false positive diagnosis in the multivariate analysis. Most of these cases had short (52.6%) or irregular (39%) ITC in SS-OCT images. CONCLUSIONS: We found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.

PURPOSE: To investigate whether anti-vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR. METHODS: Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level ≥61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization. RESULTS: The 1-year cumulative probability of TRD was 6.8% (95% confidence interval: 4.6%-9.9%, 25 events) in control-group eyes and 4.8% (95% confidence interval: 3.2%-7.3%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95% confidence interval: 0.54-1.66, P = 0.86]). The cumulative probability of vitrectomy for TRD was 4.4% (16 events) in control-group eyes and 2.2% (9 events) in anti-VEGF group eyes (P = 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity. CONCLUSION: These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.

One question that has intrigued cell biologists for many years is, "How do cells interact to influence one another's activity?" The discovery of extracellular vesicles (EVs) and the fact that they carry cargo, which directs cells to undergo changes in morphology and gene expression, has revolutionized this field of research. Little is known regarding the role of EVs in the cornea; however, we have demonstrated that EVs isolated from corneal epithelial cells direct corneal keratocytes to initiate fibrosis. Intriguingly, our data suggest that EVs do not penetrate epithelial basement membrane (BM), perhaps providing a mechanism explaining the importance of BM in the lack of scarring in scrape wounds. Since over 100-million people worldwide suffer from visual impairment as a result of corneal scarring, the role of EVs may be vital to understanding the mechanisms of wound repair. Therefore, we investigated EVs in ex vivo and in vivo-like three-dimensional cultures of human corneal cells using transmission electron microscopy. Some of the major findings were all three major cell types (epithelial, fibroblast, and endothelial cells) appear to release EVs, EVs can be identified using TEM, and EVs appeared to be involved in cell-cell communication. Interestingly, while our previous publication suggests that EVs do not penetrate the epithelial BM, it appears that EVs penetrate the much thicker endothelial BM (Descemet's membrane). These findings indicate the huge potential of EV research in the cornea and wound healing, and suggest that during homeostasis the endothelium and stromal cells are in communication. Anat Rec, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.