PURPOSE: To evaluate the timing of ocular hypertension (OHT) after pediatric closed-globe injury (CGI) and traumatic hyphema. We hypothesize that OHT will occur at different times based on injury characteristics. DESIGN: Retrospective, cohort study. METHODS: Setting: Single-center, tertiary-care, pediatric hospital. PARTICIPANTS: Subjects included patients ≤18 years of age at the time of injury who suffered CGI and traumatic hyphema between 2002 and 2019. Observation Procedure(s): Intraocular pressure and injury demographics were abstracted for every visit after injury. OHT was defined as >21 mm Hg at presentation or after a reading of ≤21 mm Hg at a prior visit. MAIN OUTCOME MEASURES: The primary outcome measure was the timing of OHT categorized into 4 periods: presentation, acute (days 1-7), subacute (days 8-28), or late (day >28). Secondary outcome measures were identification of risks factors for OHT by multivariable logistic regression. RESULTS: OHT occurred in 119 of the 305 (39%) subject eyes. OHT occurred in 35 patients at presentation, 69 times acutely, 35 times subacutely, and 36 times late. Pupil damage predicted acute-period OHT (P = .004). OHT at presentation predicted subacute period OHT (P = .004). Iridodialysis and cataract predicted late-period OHT (P = .007 and P < .001, respectively). CONCLUSIONS: OHT after CGI and traumatic hyphema in pediatric patients is common. Injury demographics predict this complication. Integration of these risk factors with current literature allows proposal of a risk-stratification tool to guide efficient surveillance for OHT.

When ionizing irradiation interacts with a media, it can form reactive species that can react with the constituents of the system, leading to eradication of bioburden and sterilization of the tissue. Understanding the media's properties such as polarity is important to control and direct those reactive species to perform desired reactions. Using ethanol as a polarity modifier of water, we herein generated a series of media with varying relative polarities for electron beam (E-beam) irradiation of cornea at 25 kGy and studied how the irradiation media's polarity impacts properties of the cornea. After irradiation of corneal tissues, mechanical (tensile strength and modulus, elongation at break, and compression modulus), chemical, optical, structural, degradation, and biological properties of the corneal tissues were evaluated. Our study showed that irradiation in lower relative polarity media improved structural properties of the tissues yet reduced optical transmission; higher relative polarity reduced structural and optical properties of the cornea; and intermediate relative polarity (ethanol concentrations = 20-30% (v/v)) improved the structural properties, without compromising optical characteristics. Regardless of media polarity, irradiation did not negatively impact the biocompatibility of the corneal tissue. Our data shows that the absorbed ethanol can be flushed from the irradiated cornea to levels that are nontoxic to corneal and retinal cells. These findings suggest that the relative polarity of the irradiation media can be tuned to generate sterilized tissues, including corneal grafts, with engineered properties that are required for specific biomedical applications. STATEMENT OF SIGNIFICANCE: Extending the shelf-life of corneal tissue can improve general accessibility of cornea grafts for transplantation. Irradiation of donor corneas with E-beam is an emerging technology to sterilize the corneal tissues and enable their long-term storage at room temperature. Despite recent applications in clinical medicine, little is known about the effect of irradiation and preservation media's characteristics, such as polarity on the properties of irradiated corneas. Here, we have showed that the polarity of the media can be a valuable tool to change and control the properties of the irradiated tissue for transplantation.

In vivo therapeutic gene transfer has emerged as a novel class of medicines. Its feasibility relies on the safe and efficacious delivery of genetic cargo to the appropriate targets. The adeno-associated virus (AAV) vector manifested itself as a preferred gene delivery vehicle enabling therapeutic gene expression for several clinical indications. Here, we cover the recent trends in AAV capsid engineering to enhance its targeting specificity, safety, and endurance. While each and every desirable trait can be individually remodeled, combining several attributes in one capsid amounts to a significant engineering challenge. Taking advantage of virion structure and phylogenetics, harnessing directed evolution, sequence analyses, and machine learning, researchers develop novel capsid variants to realize the goals of safe and enduring gene therapy.

BACKGROUND: There are still many research challenges and unanswered questions in relation to Epstein-Barr virus-associated uveitis. These include the presence of Epstein-Barr virus (EBV) DNA in asymptomatic patients, its pathogenicity in the uveitis eye, and the role of antiviral therapy for EBV-associated intraocular inflammation. METHODS: This was a retrospective review of prospectively collected data from the Ophthalmology Department, Rajavithi Hospital between 2015 and 2020. A qualitative assay using multiplex real-time PCR was performed to detect pathogen genes from specimens obtained from a total of 344 patients. The main outcome measure was treatment success defined by clinical improvement and absence of viral DNA confirmed by PCR. RESULTS: Of the 35 cases, 24 with complete data were enrolled in the study, including 22 with post-treatment PCR results. Sixty-seven percent were HIV-infected, and other plausible causes or coinfection with other pathogens were found in 75% of patients. Cytomegalovirus (38%) was the most common co-infecting pathogen. The most commonly employed regimen was a combination of systemic acyclovir and intravitreal ganciclovir injection (58%). Of the 22 cases who had post-treatment PCR results, absence of detection of the virus by PCR in the intraocular fluid after treatment was demonstrated in 73% of patients. CONCLUSION: Patients with EBV infection can be simultaneously co-infected with other pathogens. Systemic acyclovir and ganciclovir achieved clinical improvement in most cases, and EBV infection was cured in the majority of patients.

PURPOSE: To identify genetic variants associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) in unrelated patients and to further understand the genetic and potentially causal relationships between PDS and associated risk factors. DESIGN: A 2-stage genome-wide association meta-analysis with replication and subsequent in silico analyses including Mendelian randomization. PARTICIPANTS: A total of 574 cases with PG or PDS and 52 627 controls of European descent. METHODS: Genome-wide association analyses were performed in 4 cohorts and meta-analyzed in 3 stages: (1) a discovery meta-analysis was performed in 3 cohorts, (2) replication was performed in the fourth cohort, and (3) all 4 cohorts were meta-analyzed to increase statistical power. Two-sample Mendelian randomization was used to determine whether refractive error and intraocular pressure exert causal effects over PDS. MAIN OUTCOME MEASURES: The association of genetic variants with PDS and whether myopia exerts causal effects over PDS. RESULTS: Significant association was present at 2 novel loci for PDS/PG. These loci and follow-up analyses implicate the genes gamma secretase activator protein (GSAP) (lead single nucleotide polymorphism [SNP]: rs9641220, P = 6.0×10-10) and glutamate metabotropic receptor 5 (GRM5)/TYR (lead SNP: rs661177, P = 3.9×10-9) as important factors in disease risk. Mendelian randomization showed significant evidence that negative refractive error (myopia) exerts a direct causal effect over PDS (P = 8.86×10-7). CONCLUSIONS: Common SNPs relating to the GSAP and GRM5/TYR genes are associated risk factors for the development of PDS and PG. Although myopia is a known risk factor, this study uses genetic data to demonstrate that myopia is, in part, a cause of PDS and PG.

SIGNIFICANCE: Binocular treatment for unilateral amblyopia is an emerging treatment that requires evaluation through a randomized clinical trial. PURPOSE: To compare change in amblyopic eye visual acuity (VA) in children aged 4 to 6 years treated with the dichoptic binocular Dig Rush iPad game plus continued spectacle correction vs. continued spectacle correction alone. METHODS: Children (mean 5.7 years) were randomly assigned to home treatment for 8 weeks with the iPad game (n = 92, prescribed 1 hour/day, 5 days/week or continued spectacle correction alone n = 90) in a multi-center randomized clinical trial. Prior to enrollment, children wearing spectacles were required to have at least 16 weeks of wear or no improvement in amblyopic-eye VA (< 0.1 logMAR) for at least 8 weeks. Outcome was change in amblyopic-eye VA from baseline to 4 weeks (primary) and 8 weeks (secondary) assessed by masked examiner. RESULTS: 182 children with anisometropic (63%), strabismic (16%) (<5[INCREMENT] near, simultaneous prism and cover test), or combined-mechanism (20%) amblyopia (20/40 to 20/200, mean 20/63) were enrolled. After 4 weeks, mean amblyopic VA improved 1.1 logMAR lines with binocular treatment and 0.6 logMAR lines with spectacles alone (adjusted difference = 0.5 lines; 95.1% CI: 0.1 to 0.9). After 8 weeks, results (binocular treatment: mean amblyopic-eye VA improvement = 1.3 logMAR lines vs. 1.0 logMAR lines with spectacles alone, adjusted difference = 0.3 lines; 98.4% CI: -0.2 to 0.8) were inconclusive because the confidence interval included both zero and the pre-defined difference in mean VA change of 0.75 logMAR lines. CONCLUSIONS: In 4- to 6-year-old children with amblyopia, binocular Dig Rush treatment resulted in greater improvement in amblyopic-eye VA over 4 weeks but not 8 weeks. Future work is required to determine if modifications to the contrast increment algorithm or other aspects of the game or its implementation could enhance the treatment effect.

BACKGROUND: Variants in RCBTB1 were recently described to cause a retinal dystrophy with only eight families described to date and a predominant phenotype of macular atrophy and peripheral reticular degeneration. Here, we further evaluate the genotypic and phenotypic characteristics of biallelic RCBTB1-associated retinal dystrophy in a North American clinic population. METHODS: A retrospective analysis of genetic and clinical features was performed in individuals with biallelic variants in RCBTB1. RESULTS: Three unrelated individuals of French-Canadian descent with rare biallelic RCBTB1 variants were identified. All individuals shared a novel p.(Ser342Leu) missense variant; one patient was homozygous whereas the other two each possessed a second unique novel variant p.(Gln120*) and p.(Pro224Leu). All three had macula-predominant disease with symptom onset in the fifth decade of life. CONCLUSION: This report adds to the genetic diversity of RCBTB1-associated disease. These cases confirm the later-onset, relative to many other retinal dystrophies, and macular focus of disease described in most cases to-date. They are thus a reminder of considering hereditary disease in the differential for later-onset macular atrophy.

Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

OBJECTIVES: To analyze the top 100 cited papers on ophthalmic trauma. METHODS: A literature search of Ophthalmology journals within the ISI Web of Science database for the most cited papers related to ophthalmic trauma. RESULTS: The most cited articles were published between 1943 and 2013, the greatest number being published in 2000. Ophthalmology (45), Archives of Ophthalmology (17), and the American Journal of Ophthalmology (15) published most of the articles. The institutions with the highest number of publications were Wilmer Eye Institute (10) and Massachusetts Eye and Ear Infirmary (7). Sixty-seven percent of the articles originated from the USA. The most common type of trauma studied was non-open-globe injuries and the most frequent topic studied were pathological conditions secondary to trauma (34), particularly endophthalmitis (8), and optic neuropathy (6). Articles presenting a standardized classification system for eye injury received the highest average of citations per publication. Types of research most frequently cited were observational clinical studies (62) and epidemiological studies (30); the least frequent were clinical trials (2). CONCLUSION: This bibliographic study provides a historical perspective of the literature and identifies trends within the most highly influential papers on ophthalmic trauma. Many of these articles emerged within the past three decades and came from Ophthalmology journals that remain high impact to this day. Clinical trials have been difficult to conduct and are lacking, reflecting a critical need in ophthalmic trauma research, as most of our understanding of ophthalmic trauma comes from observational and epidemiological studies.