Glaucoma, characterized by the loss of retinal ganglion cells (RGCs), is a leading cause of blindness for which there are no neuroprotective therapies. To explore observations of elevated homocysteine in glaucoma, we elevate vitreous homocysteine, which increases RGC death by 6% following ocular hypertension. Genetic association with higher homocysteine does not affect glaucoma-associated outcomes from the UK Biobank and serum homocysteine levels have no effect on glaucomatous visual field progression. This supports a hypothesis in which elevated homocysteine is a pathogenic, rather than causative, feature of glaucoma. Further exploration of homocysteine metabolism in glaucoma animal models demonstrates early and sustained dysregulation of genes involved in one-carbon metabolism and the interaction of essential cofactors and precursors (B6, B9, B12, and choline) in whole retina and optic nerve head and RGCs. Supplementing these provides neuroprotection in an acute model and prevents neurodegeneration and protects visual function in a chronic model of glaucoma.

INTRODUCTION:Visual acuity (VA) and intraocular pressure (IOP) measurements are crucial indicators of ocular health. However, the documentation of these vital parameters in clinical notes often lacks standardisation. The aim of this study was to evaluate the feasibility of using of large language models (LLMs) for automated extraction of VA and IOP data from unstructured ophthalmology clinic notes. METHOD:Outpatient clinic notes from The Queen Elizabeth Hospital Ophthalmology department were analysed using a 70 billion parameter LLaMA-3 model in a zero-shot learning approach. Nine data points per eye were extracted, including various VA measurements, IOP, and measurement methods. Results were compared to expert-verified ground truth data. RESULTS:Sixty-nine outpatient clinic notes were collected. Locally deployed LLM analysis of clinic notes was feasible. High accuracy was observed in extracting best corrected VA and IOP (above 90% for both eyes). Performance varied for other measurements, with lower accuracy for uncorrected VA (67-75%) and challenges in interpreting ambiguous documentation. The model struggled to identify assumed uncorrected VA cases, highlighting issues which may correlate with documentation clarity. CONCLUSION:This study has demonstrated that it is feasible to deploy a LLM locally to extract VA data from free-text notes. However, the accuracy of extracted data was lacking in several domains. These performance issues highlight that further research is required to optimise the accuracy of the retrieved data.

Genetic testing for paediatric cataract detects a cause in 50%-70% of affected children but is as low as 20% in some reports. We screened 180 cataract-related genes in 22 children (from 20 families) with paediatric cataract from Myanmar using whole-exome sequencing. Pathogenic or likely pathogenic variants were identified in 45% (9/20) of probands in genes MIP, COL2A1, NHS, GJA8, GJA3, CRYGC, CRYBB2, PAX6 and SLC7A8. Variants of uncertain significance likely to be important were identified in three children for a maximum diagnostic rate of 12/20 probands (60%) comparable to other reports. This is the first study to examine the genetics of paediatric cataract in Myanmar.

BACKGROUND:To (a) analyse, compare and learn from the global variations in ophthalmology training applicant selection criteria, specifically CV assessment, and (b) provide a discussion of evidence supporting such selection criteria. METHODS:An observational analysis on the selection criteria used to assess candidates applying to ophthalmology training programs within the US, Canada, European Union / European Economic Union (EU/EEA), United Kingdom (UK) and Australia and New Zealand (ANZ). Presence of a publicly available selection criteria policy for the 2025 intake was searched for on national and local college, society, federation and training program websites. The selection criteria employed for assessing applicant CV, and its associated scoring (if existent), were recorded for the included programs. Descriptive statistics was applied to these data. RESULTS:174 accredited ophthalmology training programs were identified, and 51/174 publish a publicly available selection criteria policy. Overall, the most important criteria from ophthalmic training bodies in the Western world include research experience, academic achievements, particularly in the form of awards and prizes, references supporting evidence of favourable personal and professional characteristics, and evidence of involvement in extracurricular activities that produce evidence of a well-founded interest in ophthalmology. CONCLUSIONS:Each region adopts varying selection processes and frameworks, which, rather than reflect a standardised international approach to selecting an "ideal" ophthalmology trainee, perhaps select for the specific needs of the country and or training program. The study is limited by its observational nature.

To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress – all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.

Purpose: To explore patient and service provider perceptions on diabetic retinopathy (DR), its treatment and barriers faced by patients when accessing care, in order to develop strategies to improve uptake and outcomes of DR treatment care pathway. Study Design: A qualitative study based on 12 focus group discussions (FGDs) and 8 semi-structured interviews (SSIs) was conducted. Methods: Patients were selected from three treatment care pathways: intra-vitreal injections, laser photocoagulation and vitrectomy in a tertiary care public eye hospital. Separate FGDs were conducted for males and females, as well as Sinhalese and Tamil patients, within each treatment method to examine how gender and ethnicity influenced treatment experiences and health seeking behavior. FGDs were conducted in the two main native languages separately by two experienced sociologists. The SSIs were conducted with doctors and nurses in a language preferred by each healthcare worker. A pre-defined topic guide was used in the conduction of FGDs and SSIs. The recordings of these FGDs and SSIs were transcribed and subsequently used to conduct a thematic analysis using the Socio-Ecological Model and the health systems approach as a guide. Recurring concepts were identified by review of the transcripts which informed the development of a thematic code book. Results: A total of 73 patients participated in the FGDs with a majority being male (54.7 %, n = 40) while Sinhala was the language spoken by most (60.2 %, n = 44). A total of four doctors and four nurses were interviewed in the SSIs. The lack of knowledge on diabetes, DR and DR treatment modalities was identified as a key barrier to seeking early care and a significant contributor to patient dissatisfaction. In addition, inadequacy of infrastructure, lack of wayfinding signage systems in the hospital, behavior of healthcare assistants, discrimination, long waiting times, postponement of surgeries and inadequacy of information given by doctors were among many other sub-themes that were identified as barriers. Interviews with healthcare workers revealed lack of public awareness, overcrowding, lack of proper referral systems and inadequacy of opportunities for continuous professional development as major barriers. Conclusion: Multi-dimensional factors at all levels of the Socio-Ecological Model were found to act as barriers to patient care, principal among which was the lack of knowledge among patients on the impact of diabetes on the eye. Tailormade strategies to address these barriers should be implemented in order to improve quality of care. Patient education, staff training and infrastructure development should be the cornerstones among such measures.

Age-related macular degeneration (AMD) is associated with chronic inflammation of the retinal pigment epithelium (RPE) and elevated cytokines including TNFα, TGF-β, IL-6, and IL-1β. As a metabolic intermediary supporting aerobic glycolysis in the adjacent photoreceptors, the RPE’s metabolic responses to inflammation and the optimal methods to study cytokine-driven metabolic programming remain unclear. We performed a rigorous comparison of ARPE-19 cells and rat eyecup metabolomes, revealing key distinctions. Rat eyecups exhibit higher levels of lactate and palmitate but depleted glutathione and high-energy nucleotides. Conversely, ARPE-19 cells are enriched with high-energy currency metabolites and the membrane phospholipid precursors phosphocholine and inositol. Both models showed contrasting responses to individual cytokines: ARPE-19 cells were more sensitive to TNFα, while eyecups responded more strongly to TGF-β2. Notably, a combined cytokine cocktail elicited stronger metabolic effects on ARPE-19 cells, more potently impacting both metabolite abundance (41 vs. 29) and glucose carbon flux (29 vs. 5), and influencing key RPE metabolites such as alanine, glycine, aspartate, proline, citrate, α-ketoglutarate, and palmitate. Overall, these findings position ARPE-19 cells as a more responsive platform for studying inflammatory cytokine effects on RPE metabolism and reveal critical RPE metabolites which may be linked with AMD pathogenesis.

Although the indications for retinal laser have diminished over the past 2 decades due to the rise of intravitreal injection therapy, retinal laser remains a useful clinical tool, with novel laser technologies continuing to emerge. Continuous wave photocoagulation remains the most well-characterized laser in terms of its histopathological effects. Information about the histological effects of newer retinal laser modalities is relatively scarce. Available evidence supports the notion that short pulse applications result in less collateral damage to the neurosensory retina, but that at sufficient energy settings thermal injury is observed irrespective of the laser type.

A small, azobenzene, photoswitch molecule (KIO-301) that renders retinal ganglion cells responsive to light was investigated for safety and activity in a first-in-human, phase 1/2, open-label, dose-escalation clinical trial in individuals with advanced retinitis pigmentosa. KIO-301 was delivered by intravitreal injection to 12 eyes of 6 participants. The primary endpoint was safety. Secondary endpoints included assessment of functional vision, visual acuity, kinetic visual field, functional magnetic resonance imaging (fMRI) and participant reported outcomes. There were no drug-related adverse events. A participant with no light perception at baseline recovered light perception by 2 days post injection. Visual function, including navigational ability, displayed a trend of improvement. By day 2-14 post injection the fMRI signal to visual stimuli in the primary visual cortex was enhanced and decayed over the ensuing 3 weeks. Participant-reported quality of life improved. The excellent safety profile and evidence supporting proof-of-principle has motivated a larger, randomized controlled trial.

PURPOSE:Oxidative injury has been implicated in a range of common retinal neurodegenerative disorders. Protecting the retina from such an insult could therefore prove clinically beneficial. We sought to investigate whether glucose, acting via the pentose phosphate pathway (PPP), was able to counteract oxidative cytotoxicity to retinal cells in culture. EXPERIMENTAL:Mixed retinal neuron-glial cultures were prepared from Sprague-Dawley rat neonates and used at 7 days in vitro; neuron-only and Müller glial cell-only mono-cultures were subsequently prepared from these cultures. At appropriate stages, cultures were treated with t-butyl hydroperoxide (tbH; 10 nM-1 mM) in glucose/pyruvate-free DMEM to induce oxidative stress. Some cultures were co-treated with glucose. Additional compounds were co-applied to inhibit glycolysis, PPP, cystine uptake, glutathione biosynthesis and glutathione reductase (GR). The effect of glucose on stimulation of reactive oxygen species (ROS), as well as levels of glutathione and NADPH were also investigated. RESULTS:Oxidative stress resulted in cytotoxicity to both retinal neurons and glial cells. Glucose was able to abrogate the toxicity to glial cells in mono-cultures and mixed cultures, but could only provide protection to neurons in the mixed cultures when glial cells were also present. Glucose was additionally shown to prevent stimulation of ROS and oxidative stress-induced depletions of glutathione and NADPH. Inhibition of PPP, cystine uptake or GR all diminished the protective response of glucose. CONCLUSION:Glucose prevented oxidative stress to retinal cells via the PPP. Neurons were not subjected to glucose-induced protection except when glial cells were present, implying the passage of a transmissible mediator or other protective action between the two cell types.

BACKGROUND:In 2024, WHO included effective refractive error coverage (eREC) into the results framework of the 14th General Programme of Work, which sets a road map for global health and guides WHO's work between 2025 and 2028. eREC is a measure of both the availability and quality of refractive correction in a population. This study aimed to model global and regional estimates of eREC as of 2023 and evaluate progress towards the WHO global target of a 40 percentage-point absolute increase in eREC by 2030. METHODS:For this systematic review and meta-analysis, the Vision Loss Expert Group analysed data from 237 population-based eye surveys conducted in 76 countries since 2000, comprising 815 273 participants, to calculate eREC (met need / met need + undermet need + unmet need]) and the relative quality gap between eREC and REC ([REC - eREC] / REC × 100, where REC = [met + undermet need] / [met need + undermet need + unmet need]). An expert elicitation process was used to choose covariates for a Bayesian logistic regression model used to estimate eREC by country-age-sex grouping among adults aged 50 years and older. Country-age-sex group estimates were aggregated to provide estimates according to Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions. FINDINGS:Global eREC was estimated to be 65·8% (95% uncertainty interval [UI] 64·7-66·8) in 2023, 6 percentage points higher than in 2010 (eREC 59·8% [59·4-60·2]). There were marked differences in eREC between GBD super-regions in 2023, ranging from 84·0% (95% UI 83·0-85·0) in high-income countries to 28·3% (26·4-30·4) in sub-Saharan Africa. In all super-regions, eREC was lower in females than males, and decreased with increasing age among adults aged ≥50 years. Since 2000, the relative increase in eREC was 60·2% in sub-Saharan Africa, 45·7% in North Africa and the Middle East, 41·5% in southeast Asia, east Asia and Oceania, 40·3% in south Asia, 16·2% in Latin America and the Caribbean, 8·3% in central Europe, eastern Europe and central Asia, and 6·8% in the high-income super-region. The relative quality gap ranged from 2·9% to 78·3% across studies, with larger gaps characteristically in regions of lower eREC. Globally, the percentage of those with a refractive need that was undermet reduced between 2000 and 2023, from 10·0% (95% UI 9·5-10·5) to 5·3% (5·1-5·5). INTERPRETATION:The current trajectory of improvement in eREC and the relative quality gap are insufficient to meet the 2030 target. Global efforts to equitably increase spectacle coverage, such as the WHO SPECS 2030 initiative, and to address equity failings associated with geography, age, and sex, are crucial to accelerating progress towards the 2030 targets. No region is close to achieving universal coverage. FUNDING:WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, University of Heidelberg, German Federal Ministry for Education and Research. TRANSLATIONS:For the French, Chinese and Spanish translations of the abstract see Supplementary Materials section.

PURPOSE:Pseudoexfoliation syndrome (PEX) is a known risk factor for glaucoma, but its individual clinical course ranges from no glaucoma to total blindness. This study investigated whether polygenic risk scores (PRSs) built from variants collectively associated with open-angle glaucoma, intraocular pressure (IOP), and vertical cup-to-disc ratio (VCDR) can stratify individuals with pseudoexfoliation for the risk of glaucoma development. DESIGN:Retrospective multicohort study of 2 glaucoma registries and 1 population-based cohort. PARTICIPANTS:For the primary analysis, participants (n = 828) were classified as having PEX with glaucoma, PEX with suspected glaucoma, or PEX with no glaucoma. For the secondary analysis, a cohort of participants (n = 2460) were classified as having PEX with glaucoma, having PEX with no glaucoma, and being unaffected, and an independent cohort of participants (n = 3372) were classified as having primary open-angle glaucoma (POAG) or suspected POAG. METHODS:Previously published and validated PRSs for open-angle glaucoma, IOP, and VCDR were expressed as a percentile, decile, or tertile of an ancestrally matched healthy population. Multivariable logistic and linear regressions and survival analyses were performed. MAIN OUTCOME MEASURES:The main outcome measures were odds of pseudoexfoliative glaucoma (PEX-G) and odds of clinically relevant outcomes. RESULTS:Participants in the top tertile of the glaucoma PRS showed greater odds of receiving a PEX-G diagnosis (adjusted odds ratio [aOR], 4.22; 95% confidence interval [CI], 2.62-6.88; P < 0.001), greater odds of bilateral central vision loss (aOR, 3.43; 95% CI, 1.49-8.99; P = 0.007), and greater odds of bilateral incisional surgery (aOR, 3.35; 95% CI, 1.33-10.24; P = 0.018). Age at PEX-G diagnosis was 1 year younger with each increasing glaucoma PRS decile (1.06 years; 95% CI, 0.59-1.53 years; P < 0.001). Participants with manifest glaucoma and pseudoexfoliation showed a comparatively lower glaucoma PRS than counterparts with POAG. CONCLUSIONS:The PRSs for open-angle glaucoma, IOP, and VCDR stratify risk of glaucoma development and disease severity among individuals with PEX. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.