Eye

PurposeTo investigate the epidemiology of post-injection endophthalmitis (PIE) and evaluate the association of sociodemographic and clinical factors with incidence, timing of onset, and presenting visual acuity (VA) using the IRIS(R) Registry (Intelligent Research in Sight). DesignRetrospective cohort study. ParticipantsPatients with endophthalmitis after an intravitreal anti-VEGF injection in the IRIS(R) Registry from 2016-2023. MethodsOnly the first anti-VEGF injection per eye was included. Exclusion criteria were cataract surgery during the study, intravitreal corticosteroids within 30 days prior to PIE, uveitis, or cystoid macular edema. Mean best VA was recorded within 100 days prior to anti-VEGF treatment and at the time of PIE. Regression modeling evaluated associations between endophthalmitis and sociodemographic and clinical factors, and time to PIE. Linear regression assessed predictors of VA at the time of PIE, and descriptive statistics were used to analyze time to onset. Main Outcome MeasuresIncidence of post-injection endophthalmitis, time to symptom onset, and best VA at diagnosis. ResultsAmong 1,025,788 eyes treated, 600 (0.059%) developed endophthalmitis. Key risk factors included residence in U.S. territories (OR = 2.62; P = 0.038 vs. Northeast) and history of intravitreal corticosteroid injection (OR = 2.35; P = 0.004 vs. no history). The strongest protective factor was non-smoking (OR = 0.71; P = 0.023 vs. smokers). The median time from injection to onset of PIE was 5 days (interquartile range [IQR]: 3-8). The salient predictors of time to PIE included patient age (4.3 days sooner per decade older; P = 0.04), prior corticosteroid treatment (11.7 days sooner; P = 0.02), and a diagnosis of diabetic retinopathy (2.3 days sooner; P=0.03). Baseline VA before PIE was the only significant predictor of VA at the time of PIE diagnosis (0.67, P < 0.001). ConclusionPost-injection endophthalmitis was significantly associated with residence in U.S. territories and prior intravitreal corticosteroid exposure, while non-smoking status was protective. Most cases presented 3-8 days following anti-VEGF injection. Older age, history of prior corticosteroid treatment, and diabetic retinopathy were associated with earlier PIE. Baseline VA predicted VA at the time of PIE.

BackgroundDiabetes mellitus (DM) remains a major global health challenge and is associated with vision-threatening complications, including diabetic macular edema (DME), a leading cause of visual impairment. Dyslipidemia has been implicated in the development of macular edema through mechanisms involving vascular permeability, endothelial dysfunction, and chronic inflammation. However, evidence regarding the relationship between lipid abnormalities and macular edema remains inconsistent across studies. AimThis study aimed to evaluate the association between abnormal lipid profiles and diabetic macular edema among patients with type 2 diabetes mellitus attending Kilimanjaro Christian Medical Centre (KCMC). MethodsA hospital-based analytical cross-sectional study was conducted among 296 diabetic outpatients at KCMC. Participants underwent comprehensive ophthalmic evaluation including fundoscopy and imaging with optical coherence tomography (OCT) for assessment of macular edema. Blood samples were collected for biochemical lipid analysis. Data were cleaned and analyzed using STATA version 17. ResultsDiabetic macular edema was identified in 56.4% (167/296) of participants. Abnormal lipid parameters were common, with elevated total cholesterol observed in 48.6%, triglycerides in 43.6%, low-density lipoprotein (LDL) in 36.1%, and reduced high-density lipoprotein (HDL) in 38.9% of patients. Elevated total cholesterol, triglycerides, and LDL levels showed significant associations with macular edema (p < 0.05). After multivariable adjustment, serum triglycerides remained independently associated with macular edema (p = 0.002). ConclusionDyslipidemia demonstrated a significant association with diabetic macular edema, with serum triglycerides emerging as an independent predictor. These findings highlight the importance of lipid monitoring, lifestyle modification, and strengthened screening strategies in reducing the burden of vision-threatening diabetic complications.

IntroductionAnti-vascular endothelial growth factor (anti-VEGF) therapies are standards of care for vision-threatening retinal diseases. This retrospective observational study describes demographics, utilization, best recorded visual acuity (BRVA), and safety among eyes with neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), or retinal vein occlusion (RVO) treated with the biosimilar aflibercept-ayyh (PAVBLU(R)) in routine clinical practice. MethodsElectronic medical records from the Retina Consultants of America database of patients receiving aflibercept-ayyh (12/1/2024-10/31/2025) were analyzed, focusing on eyes with [&ge;]84 days of follow-up. The index date was the first documented aflibercept-ayyh injection. Postindex data were used to assess treatment patterns, BRVA (Wilcoxon signed rank test), and adverse events of special interest (AESIs). ResultsA total of 1,000 consecutive eyes from 989 patients received 3,730 injections of aflibercept-ayyh; most (91%) switched from prior anti-VEGF therapy and 9% were anti-VEGF treatment-naive. Disease distribution was 58% nAMD, 19% RVO, 16% DME, and 7% DR. Among switchers, median (IQR) number of prior injections was 21 (8-46). Median (IQR) follow-up was 6.0 months (4.6-7.1). Median (IQR) number of aflibercept-ayyh injections per eye was 4 (3-5). Among eyes with [&ge;]84 days of follow-up (n=889), mean BRVA expressed as logarithm of minimum angle of resolution (logMAR) remained stable for switchers (0.4 to 0.4; P=0.96) and improved from baseline in anti-VEGF-naive eyes (0.5 to 0.4; P<0.01). Confirmed AESIs included iritis (n=2; 0.05% of injections), with no events of vitreous cells, endophthalmitis, retinal detachment, retinal vasculitis, or vitreous hemorrhage. ConclusionIn this descriptive real-world analysis, aflibercept-ayyh was associated with stable visual acuity in previously treated eyes and vision improvement in treatment-naive eyes, with no new or unexpected safety findings, consistent with expectations for aflibercept. These findings add real-world experience to preexisting evidence demonstrating no clinically meaningful differences between aflibercept-ayyh (PAVBLU(R)) and reference aflibercept (EYLEA(R)). KEY SUMMARY POINTSO_ST_ABSWhy carry out this study?C_ST_ABSO_LIThe anti-vascular endothelial growth factor (VEGF) drug aflibercept, approved in 2011 and marketed in the United States as EYLEA(R),* has demonstrated efficacy in treating retinal diseases such as neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), or retinal vein occlusion (RVO) and is a standard of care for these disorders. C_LIO_LIAflibercept-ayyh is a biosimilar to aflibercept that has demonstrated comparable efficacy and safety in the treatment of nAMD in a randomized controlled clinical trial. C_LIO_LIThis study describes the real-world use patterns, vision outcomes, and safety of aflibercept-ayyh in clinical settings in the United States for the treatment of nAMD, DR, DME, and RVO. C_LI What was learned from the study?O_LIIn this real-world study of 1,000 consecutive eyes treated with the biosimilar aflibercept-ayyh in patients with retinal diseases, we observed no new safety concerns and that aflibercept-ayyh maintained visual acuity in eyes switching anti-VEGF agents and improved vision in anti-VEGF-naive eyes, consistent with expected responses to aflibercept. C_LIO_LIThese findings support aflibercept-ayyh as a suitable treatment option when anti-VEGF therapy is indicated. *EYLEA(R) is a registered trademark of Regeneron Pharmaceuticals, Inc. PAVBLU(R) is a registered trademark of Amgen Inc. C_LI

This prospective, multicenter, real-world evidence study evaluates the 12-month safety and effectiveness of standalone cyclodialysis with AlloFlo cleft reinforcement for intraocular pressure (IOP) reduction in open-angle glaucoma (OAG). AlloFlo represents the worlds first acellular, allogenic scleral tissue implant, and data from this CREST Study cohort (NCT05506423) contribute critical long-term safety and effectiveness knowledge to the field of extracellular matrix biomaterials research, in addition to describing a novel procedure for surgical management of OAG. Eyes with investigator-confirmed inadequately controlled OAG were treated with standalone cyclodialysis using a microsurgical cannula (CycloPen), followed by uveoscleral cleft reinforcement with AlloFlo. Eyes were followed prospectively for 12 months. Key outcomes included changes in medicated IOP, number of glaucoma medications, adverse events, and progression to subsequent glaucoma procedures. Forty-one eyes of 38 patients were included. Most eyes (66%) were considered treatment-refractory, defined as having any of: failed [&ge;] 1 incisional surgery or cilioablative procedure; condition in which incisional surgery would be more likely to fail than in eyes with uncomplicated OAG. At 12 months, mean IOP decreased 31% to 14.7 {+/-} 6.9 mmHg (within the normal IOP range of 10-20 mmHg, p < 0.001); mean number of glaucoma medications decreased 32% to 1.9 {+/-} 1.6 (p < 0.001). Seventy-one percent of eyes achieved [&ge;] 20% IOP reduction (a clinically meaningful benchmark set by the FDA). More than half of eyes (53%) achieved [&ge;] 20% IOP reduction without increasing medication. Three eyes (7.2%) progressed to incisional glaucoma surgery. Postoperative IOP elevations [&ge;] 10 mmHg occurred in 17% of eyes, most of which resolved within 30 days of the procedure. No persistent inflammation, implant rejection, clinically significant hyphema, or scaffold migration occurred. These findings suggest that uveoscleral outflow enhancement with AlloFlo provides a safe, conjunctiva-sparing option for IOP reduction in OAG, including eyes with prior surgical interventions.

AimsPrimary objective: To determine the minimum inhibitory concentration (MIC) of key antifungal drugs (natamycin, amphotericin B, voriconazole and econazole) against fungal isolates cultured from fungal keratitis patients in South India. Secondary objective: to ascertain correlations between antifungal resistance and patient outcome. MethodsIn this prospective observational study, MIC values were determined for fungal isolates cultured from 153 patients, with samples collected between May - August 2025. Clinical characteristics were collected at baseline, one-week and one-month following enrolment to the study. Mean antifungal MIC per fungi genera were compared. Statistical differences in MIC and patient characteristics were determined via multiple logistic or linear regression. Significance for participant outcome against resistant/non-resistant fungi were determined by Fishers exact test. ResultsResistance of Fusarium spp. isolates to: natamycin: 38.3%; amphotericin B: 93.8%; voriconazole: 97.5% and econazole: 76.5%. Resistance of Aspergillus spp. isolates to: natamycin: 66.7%; amphotericin B: 87.9%; voriconazole: 6.1%; and none were resistant to econazole. Natamycin MIC correlated with worse baseline (P[&le;]0.01) and one-week (P[&le;]0.05) visual acuity and ulcer severity. Poor patient outcomes (non-healing or therapeutic keratoplasty) were elevated 6.5x where the infection was caused by natamycin resistant Aspergillus, compared to sensitive Aspergillus strains (P[&le;]0.05). ConclusionThe majority of fungal isolates were resistant to multiple antifungals, none of the Fusarium isolates were sensitive to all four drugs, and 15% were resistant to all four drugs. Aspergillus isolates had high levels of resistance to the polyenes, but remained largely susceptible to the azoles. Overall, worse patient outcomes were associated with increased natamycin MIC. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSFungal keratitis is a major cause of blindness worldwide, disproportionately affecting those across the tropics, with incidence increasing across temperate climates. The majority of cases are caused by the filamentous fungi Fusarium spp. and Aspergillus spp.. Antifungal resistance is poorly characterised in fungal keratitis. What this study addsWe report the fungal aetiology and the minimum inhibitory concentration (MIC) against natamycin, amphotericin B, voriconazole and econazole of isolates cultured from 153 patient corneal scrape samples between May - August 2025 at a South Indian hospital. We found high levels of fungal resistance, with Fusarium isolates having high levels of resistance to both polyenes and azoles. Aspergillus isolates showed good azole sensitivity, but high levels of resistance to polyenes. Aspergillus resistance to natamycin correlated with worse clinical outcomes at one-month. Natamycin resistance contributed to worse visual acuity and ulcer severity at baseline and one-week follow-up across all fungi. How this study might affect research, practice or policyOur study confirmed that natamycin was best available first-line treatment for Fusarium. Aspergillus isolates were mostly resistant to natamycin and amphotericin B, and this impacted patient outcomes. SynopsisWe identified high incidence of multi-drug resistant fungi, and that patients were more likely to have a poor clinical outcome if the fungal isolate was resistant to natamycin. This was most pronounced for Aspergillus isolates.

PurposeTo evaluate the efficacy and safety of Gene III L-ergothioneine (EGT) Eye Care Solution for alleviating ocular discomfort in patients with dry eye syndrome (DES). MethodsIn this single-center, randomized, open-label, self-controlled trial, 40 DES patients were randomly assigned in a 1:1 ratio to one of two treatment groups: Group 1 received the Gene III EGT Eye Care Wash Solution via an eye wash cup (5 mL/vial), and Group 2 received the same formulation as Gene III EGT Eye Care Drops Solution (0.5 mL/vial). Outcomes were assessed at baseline and after 14 days using validated scales, including the Chinese Dry Eye Questionnaire, the Ocular Surface Disease Index (OSDI), and the Comprehensive Assessment of Visual Fatigue (CAVF), along with fluorescein tear film break-up time (TBUT). ResultsCombined analysis (N = 40) demonstrated significant improvements in dry eye symptoms with mean scores decreasing from 12.50 to 10.65 (P = 0.0353). Ocular Surface Disease Index (OSDI) scores improved from 12.25 to 9.2 (P = 0.0309), and visual fatigue, assessed by the CAVF scale, decreased from 11.18 to 6.60 (P = 0.0008). Significant increases in TBUT were observed in both groups, with left eye first TBUT rising in Group 1 (P = 0.0199) and Group 2 (P < 0.0001). No treatment-related adverse events were reported. ConclusionGene III EGT Eye Care Solution effectively alleviated DES symptoms and demonstrated a favorable safety profile. Larger placebo-controlled trials are warranted to confirm these findings.

PurposeTimely detection of disease activity in chronic retinal diseases improves visual outcomes but is limited by the lack of validated systems for continuous monitoring and care management. We evaluated the real-world performance of an integrated remote physiologic monitoring and principal care management program (RemoniHealth(R)) using a self-administered multimodal retinal function test (Macustat(R)) for home monitoring. MethodsThis single-arm real-world intervention study was conducted across 33 retina practices. A total of 2,216 adults with chronic retinal diseases performed weekly home retinal function testing with integrated care management support. Primary endpoints included the annualized rate of disease progression detection, time to intervention after first flag, true positive rate, and patient adherence. Descriptive statistics and data analyses were analyzed using chi-square tests and Clopper-Pearson confidence intervals. ResultsParticipants contributed 82,644 encounters and 16,805 patient-months of monitoring. The program generated 241 alerts, including 101 Macustat flags and 135 care management prompts. Among 73 adjudicated flags, 56 were true positives and 17 false positives (PPV 76.7%). The annualized detection rate was 4 per 100 patient-years. Of confirmed events, 93% led to intravitreal injection or other major management change. Mean adherence was 72.1%, and patients with [&ge;]80% adherence had higher odds of true positivity. DiscussionThis RPM-PCM model achieved high engagement and meaningful detection of asymptomatic progression between visits, supporting the value of home monitoring for timely intervention. Translational RelevanceThese findings support scalable integration of home vision testing and care management into routine retinal practice to enable earlier intervention and improved continuity of care.

PurposeTo identify genetic variants associated with glucocorticoid (GC)-induced intraocular pressure (IOP) change using genome-wide association study (GWAS) and whole exome sequencing (WES) analyses. Methods530 participants from the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) trials were analyzed, with replication performed in an independent cohort of 588 participants from the Mass Eye and Ear/Retina Health Center (MEE/RHC). All participants were exposed to GC, primarily via intravitreal injection. IOP was measured at baseline and serially within 6 months following GC exposure. GWAS and rare variant gene burden analyses were applied, adjusting for covariates. ResultsGenetic associations for maximal IOP change within 6 months after GC exposure were evaluated. For the primary outcome across all ancestries in FAME, one variant, rs13425173 within the UBE2E3 locus reached genome-wide significance (P=2.88 X 10-8). In the FAME and MEE/RHC meta-analysis, variant rs1040227, also in the UBE2E3 locus, was significantly associated at the genome-wide level (P=2.88 X 10-8) and showed nominal significance in the MEE/RHC cohort (P=0.02). In the colocalization analyses, the significant FAME GWAS UBE2E3 locus was linked to expression regulation of this gene in six tissues including artery aorta. In gene-level analysis, UBE2E3 also demonstrated subthreshold significance (P=6 X 10-6). 532 FAME and 586 MEE/RHC participants were included in the WES gene burden analysis. One gene, MSTO1, passed false discovery rate correction for the primary outcome in FAME. ConclusionWe have identified genome-wide significant common variants associated with GC-IOP change, as well as genes and rare variants that may influence GC-induced IOP change.

PurposeTo evaluate the diagnostic performance of anterior segment optical coherence tomography (ASOCT) compared to slit lamp examination for identification of corneal perforation in microbial keratitis, and to assess ASOCT grading reproducibility. MethodsWe conducted a diagnostic concordance study of 150 eyes with microbial keratitis at a tertiary eye hospital in India. Two masked graders independently evaluated ASOCT scans for perforation, with disagreements resolved by consensus. We calculated Cohens kappa for inter-grader concordance and intra-grader repeatability. Sensitivity and specificity of slit lamp examination were calculated using ASOCT as the reference standard. Logistic regression identified factors associated with disagreement between modalities. ResultsInter-grader agreement for ASOCT was near-perfect ({kappa}=0.98; 95% CI, 0.92-1.00). ASOCT identified perforation in 24 eyes (16.0%) compared to 12 eyes (8.0%) by slit lamp examination. Using ASOCT as reference, slit lamp examination demonstrated 33.3% sensitivity (95% CI, 14.9-52.2%) and 96.8% specificity (95% CI, 93.4-99.2%). Odds of disagreement were significantly higher for eyes with stromal thinning (OR=8.19; 95% CI, 2.27-29.54), mid-stromal involvement (OR=4.44; 95% CI, 1.08-18.30), and infection within 2mm of the limbus (OR=8.81; 95% CI, 1.77-43.80). ConclusionsASOCT enables highly reproducible perforation grading and detects substantially more perforations than slit lamp examination, particularly in severe disease. These findings support ASOCT as an objective tool for clinical assessment and outcome ascertainment in microbial keratitis.

PurposeTo evaluate the three-year efficacy and safety of compound trabeculectomy for uveitic glaucoma (UG). MethodsThis retrospective study enrolled 51 patients (53 eyes) requiring compound trabeculectomy, divided into UG (25 eyes) and non-UG groups (28 eyes). Outcomes including intraocular pressure (IOP), medication use, surgical success rates, and complications were analyzed over 3 years. ResultsBaseline characteristics including age, sex, preoperative IOP and medication use were comparable (all P>0.05). At 36 months, postoperative IOP was showed no significant differences, which was 15.4{+/-}8.4 mmHg and 14.6{+/-}3.3 mmHg (P=0.73) with 54% and 55% reduction (P=0.88) in UG and non-UG groups respectively. The qualified success rate was 76.0% and 85.7% at 36 months in UG and non-UG group, and Kaplan-Meier analysis showed no significant difference. Medication reduction of UG group was significant lower than non-UG group (P=0.0058). Comparable complication rates were observed between groups (all P>0.05), yet bleb scarring and cataract progression showed elevated incidence in both cohort. ConclusionCompound trabeculectomy effectively reduced IOP and medications use in UG and non-UG. There was no significant difference in both qualified and completed success rate between UG and non-UG. Complications of filtering bleb fibrosis and cataract progression should be pay close attention for both groups.

Age related macular degeneration is known to be one of the major causes of irreversible blindness among the older generation. We present a mathematical model of partial differential equations for the therapy of this disease, which is based on the intravitreal injection of a drug into the vitreous body. For the treatment to work, the drug has to travel past the inner-limiting membrane into the retina and reduce the free vascular endothelial growth factor (VEGF) concentration by binding to at least one of the two binding sites of the VEGF molecule. Therefore, our model consists of two compartments, the vitreous and the retina. In the vitreous we employ four coupled convection-diffusion-reaction equations with an additional coupling to the underlying aqueous humor flow and four coupled diffusion-reaction equations in the retina. The resulting PDE system is solved numerically in a realistic 3D eye geometry. Temporal discretization is based on one-step theta schemes and spatial discretization is done using the Finite Element method. The numerical results are used to demonstrate the therapy concept and to analyze the drug efficacy of aflibercept and ranibizumab. The results show, among other things, that only about 20 % of the drug reaches the retina through the inner-limiting membrane and that 50 % of the VEGF concentration has been rebuilt in the retina after 38.19 days for a single ranibizumab injection.

PurposeConsidering a broad range of ambient lighting conditions may impact myopia development and dim light exposure as a potential risk factor for myopia progression, this study investigates i) light exposure pattern of Indian schoolchildren in evening hours, and ii) difference in evening light exposure patterns between myopic and non-myopic schoolchildren. Method136 Indian schoolchildren aged 9-15 years, with 46 myopes and 90 non-myopes were recruited. This study analyzed evening light exposure (6-10:00 pm) recorded using MyLyt wearable light trackers in 136 Indian schoolchildren (age range: 9-15 years). Statistical analyses were conducted to evaluate differences in average light exposure levels, maximum light exposure levels, and time spent at each various light exposure ([&le;]30 lux, >30 lux, [&le;]100 lux, and >100 lux across all the tested days) in myopic (n=46) and non-myopic (n=90) groups. ResultsThe median evening light exposure level across all participants was 27 lux, with participants spending only 2 [0-6] minutes (median [IQR]) in light levels >100 lux. Myopic children had significantly lower median light exposure levels than non-myopic children (24 [19-30] vs. 28 [21-42] lux, p=0.017), and significantly lower maximum evening light levels than non-myopes (162 [101-273] lux vs. 189 [129-396] lux, p=0.044). Additionally, myopes spent significantly less time in light levels >30 lux than non-myopes (18 [11-31] minutes vs. 30 [15-53] minutes, p=0.009). ConclusionsIndian schoolchildren spend evening hours in dim light <30 lux, below recommended illuminance for reading or studying. The significant differences in evening light exposure between myopic and non-myopic children needs further exploration for its causal relationship with myopia.

PurposeTo investigate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and nonarteritic anterior ischaemic optic neuropathy (NAION) in type 2 diabetes, examining treatment recency and cumulative duration. MethodsThis nationwide registry-based nested case-control study utilised Danish health registries (1996-2023). Among 201,776 metformin-treated adults initiating second-line antihyperglycaemic therapy, 123 incident NAION cases were matched to 4,920 controls by birth year and sex (incidence-density sampling). Conditional logistic regression estimated adjusted hazard rate ratios (HRs) for GLP-1RA exposure by recency (current 0-90 days; recent 91-365 days) and cumulative duration, adjusting for socioeconomic factors, hypertension, hypercholesterolaemia, sleep apnoea, and diabetes duration. ResultsGLP-1RA use occurred in 63/123 cases (51.2%) and 1,688/4,920 controls (34.3%). Ever use was associated with a higher NAION rate than other second-line therapies (HR 2.13, 95% CI 1.43-3.18). Current use was associated with elevated rates (HR 2.28, 95% CI 1.49-3.48), whereas the estimate for recent use was imprecise (HR 1.69, 95% CI 0.88-3.25). By cumulative duration, no clear evidence of an increase was seen within 0-[1/2] years (HR 0.80, 95% CI 0.32-2.05), and rates were highest at [1/2]-1 year (HR 3.63, 95% CI 2.06-6.40) and 1-1[1/2] years (HR 3.52, 95% CI 1.73-7.17). Findings were consistent after HbA1c adjustment and in a new-user analysis. ConclusionGLP-1RA use is associated with a higher NAION rate in type 2 diabetes. This association appears time-dependent, being most pronounced during current treatment and peaking after 6-18 months of cumulative exposure.

PURPOSEBEST1-associated inherited retinal disease constitutes one of the largest inherited retinal disease patient populations across the world. Innovative therapies are currently in development to address this significant unmet need. To better understand the scale of unmet need, and the distribution of phenotypes and genotypes, we conducted a meta-analysis of BEST1 patients reported in the literature to provide up-to-date patient number estimates. METHODSWe utilized the GeneScape(R) IRD Patient Atlas, an expertly curated database of [~]73K retinal disease patients undergoing extensive genetic testing, in combination with a dedicated literature search to estimate the proportion of IRD patients attributed to BEST1 using fixed effects weighting. This was also translated to patient number estimates for each country. Further extrapolation of patient subtypes was estimated based on cohorts of BEST1 patients reporting phenotypes and genotypes. In addition, a summary of contributing variants is reported by region. RESULTSAcross regions BEST1 retinopathy patients are estimated to occur from 1 in 38K (in Germany) to 1 in 363K in Japan. In the western countries, bi-allelic patients are expected to contribute nearly 20% of the total BEST1 population, whereas one third of patients in East Asia are anticipated to be bi-allelic. CONCLUSIONSWhile patients are reported across the world, their prevalence and composition vary across geographies. In the literature bi-allelic patients are less often reported explicitly as ARB patients in the United States as compared to Europe. Variant diversity is reflected in regional reports and drives phenotypic distribution.

PurposeQuantitative metrics obtained from retinal fundus images (such as vessel length, tortuosity and other scale-dependent measures) are increasingly used as potential biomarkers for systemic diseases, including cardio- and neurovascular conditions. However, with the increasing prevalence of myopia and related axial growth, this study aims to evaluate if axial length scaling significantly alters the overall distributions of the inferred biomarkers when compared to biomarker data obtained without axial length scaling and if these effects can be corrected. Methods2,309 clinic visits from patients aged [&le;]21 years were analysed and extracted for axial-length scaling analysis (range) 20 to 28 mm). The retinal fundus photographs were automatically segmented using Automorph to extract biometric data, including vascular metrics. The parameters were further corrected for axial length using correction factors based on the Bennett-Littmann formula and true axial length. ResultsAxial length significantly influenced biometric parameters (vessel metrics) derived from fundus photography. The magnitude of error in diameter and length of blood vessels was approximately 4-5% for each 1 mm deviation from the reference axial length of 24 mm, whereas the error in vessel area was approximately 9-10% per 1 mm, consistent with the geometric expectation that area scales with the square of linear dimensions. The scaling corrections for different axial lengths are presented. ConclusionsAxial-length-related magnification introduces systematic bias into retinal vascular metrics from fundus photographs. Bennett-Littmann correction using true axial length reduces these errors and should be adopted in quantitative fundus imaging and Al biomarker development.

PurposeMeasuring near vision provides clinicians with valuable insight into visual function. There is limited information on the accuracy of available reading charts frequently used in community practice. This study aimed to measure internationally available reading charts to determine how they compare to international standards, and develop a free chart, the UC/UWA Reading Chart, that conforms to these standards. MethodsCommercially and device manufacturer-provided reading charts were scanned at 600 dots per inch. Gaussian adaptive threshold was used to facilitate repeatable measurements. X-heights of letters were measured independently by three researchers. Other variables such as contrast levels and line spacing were also measured. Results for each chart were compared with ISO Standards. Intraclass correlation coefficient was used to assess intergrader agreement. ResultsOf the 19 reading charts that were measured, only one chart (5.26%) had text sizes that were all within tolerance. There was high variability in size observed between charts. Twelve charts (63.2%) used serif fonts and seven used sans-serif (36.8%). Text on serif charts tended to be smaller than required ({micro}=-9.65%) compared to sans-serif ({micro}=+4.96%). All charts met the line spacing requirements and minimum required contrast level; however, some charts were printed on laminated or satin plastic which does not meet the standard of using a matte surface. There was high interrater agreement (ICC(2,1) = 1.00), indicating a highly repeatable measurement technique. ConclusionThis study found that the tested reading charts displayed significant variability in text size. Although some charts had more lines of text within size tolerances than others, none met all the requirements of the International Standard. Clinicians and researchers should take care when interpreting changes in near reading acuity when multiple charts have been used, especially as part of shared care models or when monitoring progressive vision changes. Key pointsO_LINone of the measured reading charts met the requirements of the ISO 7921:2024 standard. C_LIO_LIThere is high variability in text size between reading charts. C_LIO_LIA new chart, the UC/UWA Reading Chart, has been developed to conform to the ISO standards. C_LI

PurposeVisual impairment in children is a significant public health issue, especially for those from disadvantaged backgrounds. Vision screening by schools and pediatricians have had limited success in resolving this concern. This study examined the outcomes, challenges, and demographics of the MobilEyes program, a school-based mobile eye care initiative in Rochester, New York. MethodsDuring the 2022-2023 academic year, students in PreK, K, 1st, 3rd, 5th, and 7th grade underwent visual acuity screening per New York State Guidelines. A positive screen was visual acuity <20/40 for kindergarteners or younger and <20/30 for 1st graders or older. Children who failed vision screening and whose parents provided consent for school-based eye examination subsequently underwent cycloplegic refraction and dilated fundus examination by a pediatric ophthalmologist. Demographics subgroups were analyzed by school, school region, and grade level. Results1399 students from six schools underwent vision screening, of which 387 (27.7%) failed the initial screening. From those, 125 (32.3%) returned signed parental consent forms and 108 (27.9%) underwent full eye examinations. Of this group, 68 (63.0%) were prescribed glasses, and 40 (37.0%) did not require glasses prescription and were considered false positives. Significantly more urban students failed their vision screening than suburban students, 32.8% vs 22.5% (p<0.001), and urban students had a lower false positive vision screening result (meaning that they failed their vision screening but were found to have a normal exam) than suburban students 27.6% vs 48% (p=0.047). Across all schools we found statistically significant differences between grade levels in the number failing vision screening (p<0.001) and returning consent forms (p=0.021). ConclusionOur data highlights the need for additional support of school screening and full eye examinations, especially in urban regions. Future studies should address the challenges of high vision screening false positivity percentages and obtaining parental consents to perform eye examinations.

Purpose: To determine the test-retest reliability of visual function parameters in patients with genetically confirmed Pseudoxanthoma elasticum (PXE), as a necessary step toward evaluating their suitability as outcome measures in future therapeutic trials. Methods: In this prospective natural history study (PROPXE, ClinicalTrials.gov ID: NCT05662085), patients with PXE underwent comprehensive visual function evaluation in one study eye at baseline and at a month 2 retest visit. Functional testing included light- and dark-adapted steady state microperimetry and dark-adaptometry at 8{degrees}, 15{degrees} 30{degrees}, and 46{degrees} eccentricity. Test-retest reliability was evaluated using Bland-Altman statistics. Results: Twenty-six patients (14 female, 12 male; median [IQR] age 55 years [43; 59]) with genetically confirmed PXE were included in the study. Overall, the steady-state microperimetry limits of agreement (LoA) were {+/-}2 dB for mean sensitivity and {+/-}6.8 dB for pointwise sensitivity in both scotopic (cyan and red) and mesopic conditions. The LoAs of rod intercept time as a measure of dark adaptometry were {+/-} 12 min at the inner measurement points (8{degrees} and 15{degrees}) and {+/-} 18 min at the outer measurement points (30{degrees} and 46{degrees}). Conclusions: Scotopic and mesopic microperimetry LoAs are similar to earlier published test-retest analyses in other retinal diseases. Dark-adaptometry curve parameters were markedly more variable compared to previous data in healthy volunteers. This is likely attributable to the severe dark adaptation abnormalities in PXE, leading to long test durations. Translational Relevance: The evaluation of functional biomarkers is critical for designing future clinical trials aimed at slowing PXE progression.

AimTo assess the relationship between pointwise visual field (VF) sensitivity fluctuation and localised glaucoma progression. MethodsRetrospective observational analysis of prospective cohort data from 399 participants (641 eyes) in the African Descent and Glaucoma Evaluation Study (ADAGES). Glaucoma, glaucoma suspect, and control participants underwent annual examinations including VF testing. VF fluctuation was evaluated using the pointwise standard deviation (SD) of total deviation (TD) residuals during the early 30-month period. Pointwise progression was defined independently at each location as a confirmed sensitivity loss >7 dB. The primary outcome was the association between early fluctuation and subsequent pointwise progression. We additionally evaluated whether the early pointwise rate of change (slope) strengthened this association. ResultsOf 33,332 VF points, 5.8% showed progression over 12.2 {+/-} 3.1 years. Progression occurred more frequently in glaucoma (15.6%) than in suspects (1.6%) or controls (0.4%) (p<0.0001). In glaucomatous eyes, progressive points demonstrated greater early fluctuation (median 1.75 dB; IQR 1.52-2.00) than non-progressive points (1.14 dB; IQR 0.97-1.34; p<0.0001) and faster early slopes (-0.65 vs 0.08 dB/year; p<0.0001). In multivariable mixed-effects models, higher early fluctuation ({beta} = 0.40 {+/-} 0.02; p<0.0001) and faster early slopes ({beta} = - 0.40 {+/-} 0.02; p<0.0001), but not baseline TD (p=0.92), were associated with progression. Conclusions: Greater early pointwise VF fluctuation independently predicted future localised progression. The slope analysis mirrored these findings, indicating that early functional variability reflects underlying local instability. These results support early pointwise fluctuation as a predictor of glaucoma progression and a potential endpoint for clinical trials.

The prevalence of the two types of horizontal strabismus, esotropia and exotropia, varies considerably between studies. This variability has been attributed to factors such as geography/environment, research methodology, age of study subjects, and/or ethnicity. Comprehensive estimates of regional and global prevalences of esotropia and exotropia are lacking, making it difficult to recognize true patterns, trends, and etiologies. Our systematic review compiles prevalences and ratios of esotropia to exotropia from 315 population-based studies and 374 clinic-based studies. We analyze data to assess effects of ethnicity, geography, age, and identify generational changes of horizontal strabismus. Major ethnicities differ in patterns and ratios of esotropia and exotropia prevalence, not only Caucasians and East Asians, but also Latinos/Hispanics, South Asians, Africans, and Native Americans. Compared to population-based studies, clinic-based studies underestimate exotropia frequency. By weighing prevalences according to the population size of ethnicities, we estimate the worldwide prevalence of horizontal strabismus in the current generation at 1.81% (138.5 million), comprising 60.0 million people with esotropia (0.67%) and 87.5 million with exotropia (1.14%). In the previous generation, the worldwide prevalence of horizontal strabismus was 1.64% (86.5 million people), comprising 50.5 million with esotropia (0.96%) and 36.0 million with exotropia (0.68%). Generational trends in esotropia and exotropia prevalences differ between ethnicities, indicating that extrinsic factors can modify the underlying intrinsic (genetic) disposition.