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Ophthalmology Science

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match Ophthalmology Science's content profile, based on 22 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Optimizing Aqueous Humor Liquid Biopsy: Safety and Performance of a Short, Low-Dead-Space Ophthalmic Needle for Anterior Chamber Paracentesis

Singh, A. M.; Yeh, T.-C.; DeBoer, C.; Al-Moujahed, A.; Lin, J. B.; Smith, S. J.; Sanislo, S.; Janjua, K. A.; Lin, T.-C.; Almeida, D. R. P.; Mruthyunjaya, P.; Mahajan, V. B.

2026-09-02 ophthalmology 10.64898/2026.08.26.26361364 medRxiv
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Purpose: To evaluate the safety, procedural performance, sample recovery, and surgeon preference of an ophthalmic needle designed specifically for anterior chamber (AC) paracentesis. Methods: In this multicenter study, AC paracentesis was performed in clinic and operating-room settings using a 32-gauge x 4-mm needle with low dead space. The procedure was evaluated using a standardized physician survey. Prespecified outcomes included procedure-related adverse events (primary outcome), needle entry and handling, aspiration and sample recovery, comparative performance versus a 30-gauge needle, and physician preference for future use. Results: A total of 110 needle uses by eight surgeons were included. No ocular complications occurred, including lens or iris injury, hyphema, AC collapse, wound leak, hypotony, infection, or retinal complication, and no procedure required needle exchange or conversion to another device. Two technical events without ocular sequelae were noted, in which needle entry was partial thickness and did not reach the AC (1.8%; exact 95% CI, 0.2%-6.4%). Physicians rated needle entry, handling and sample recovery as good or excellent. Compared with a 30-gauge needle, the study needle was rated as at least comparable across all assessed domains. All surgeons rated it better or much better for intra-procedural safety and preferred it for future AC taps. Conclusions and Relevance: This short, 32-gauge low-dead-space ophthalmic needle demonstrated a favorable safety profile and was preferred over a 30-gauge needle by all surgeons. As aqueous humor liquid biopsy expands in clinical diagnostics and trials, an ophthalmic-specific needle design may help improve the consistency and safety of aqueous humor collection for molecular analysis and broader clinical use. Keywords: Anterior chamber paracentesis; Aqueous humor; Liquid biopsy; Low dead space; Ophthalmic needle

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Validation of a Novel Algorithm for Automated Detection and Quantification of Choroidal and Retinal Pulsation on Video Indocyanine Green Angiography

Sahoo, N. K.; Doshi, U.; Gregori, G.; Flores-Pena, D.; Lupidi, M.; Vupparaboina, K. K.; Chhablani, J.

2026-08-12 ophthalmology 10.64898/2026.08.10.26360105 medRxiv
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Purpose: To validate an automated pipeline to detect and quantify focal retinal and choroidal pulsation areas that are synchronous with the cardiac cycle in video indocyanine green angiography (ICGA). Design: Retrospective, observational, hypothesis-generating validation study Subjects, Participants: Consecutive patients with a diagnosis of central serous chorioretinopathy (CSCR) in one or both eyes. Methods: Videos were acquired on Heidelberg HRA+OCT. The pipeline consisted of three steps: signal extraction, foci detection, and quantification. After registration of the constituent frames, each pixel's intensity signal was analyzed at the presumed cardiac frequency (tested from a sample of three detectable frequencies). A synchrony score combining local phase coherence with oscillation amplitude was then derived and computed using a standard deviation ({sigma}) above each video's background oscillation value. Two masked graders marked the retinal and choroidal pulsation areas twice. We compared detection of the pulsation areas against grader consensus using a receiver operating characteristic curve (using multiple grid sizes to divide the scan area) and, separately, using a signal-based area-reduction method to obtain an optimum {sigma} value. Main Outcome Measures: Agreement between the automated algorithm and human graders in detection of pulsation foci, and the optimum threshold multiplier ({sigma}). Results: We studied 20 ICGA videos from 20 eyes. At the 16-pixel grid size, the pipeline achieved a mean area under the curve (AUC) of 0.914, sensitivity of 0.86, and specificity of 0.80. Grader agreement improved with larger grid size, reaching substantial-to-strong levels for choroidal annotations. The two independent validation methods demonstrated similar {sigma} values that differed by 0.62{sigma}, supporting {sigma}=4.0 as the optimum value. Conclusions: We report the first automated method to quantify retinal and choroidal vascular pulsation on video ICGA. It measures pixels that oscillate over time with the presumed cardiac cycle and works reliably at the spatial scale (grid level) where experts agree. Pulsatile hemodynamics may add a new vascular biomarker for glaucoma, diabetes, hypertension, and pachychoroid diseases.

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Virtual control arms for paediatric myopia trials: external validation of axial-elongation models

Bakaraju, R. C.; Bandela, P. K.; Sha, J.; Tilia, D.

2026-08-23 ophthalmology 10.64898/2026.08.21.26360973 medRxiv
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Clinical relevance: Validated virtual control arms may provide population-level estimates of treatment effect and reduce reliance on untreated control allocations in myopia trials. Background: Untreated single-vision control arms in paediatric myopia efficacy trials are increasingly difficult to justify and retain. Several published models predict untreated childhood axial elongation by region or ethnicity. Here they are implemented unchanged in an open-source tool and validated against an untreated multi-ethnic cohort. Methods: Five published models predicted untreated elongation from baseline age, cycloplegic spherical equivalent, sex, and ethnicity, anchored at baseline axial length (AL) and evaluated at actual follow-up. Predictions were compared with 242 untreated myopic children (Chinese, Vietnamese, Indian) with AL measured at approximately 6 and 12 months, assessing bias, root-mean-square error, and prediction-interval coverage against pre-specified thresholds (bias <0.03 mm; coverage greater than or equal to 0.90). Results: The regional generalised estimating equation (GEE) and meta-regression models reproduced mean East Asian elongation without meaningful bias at 6 months (GEE bias -0.013 mm; equivalence to plus-or-minus 0.03 mm, p = 0.014) and at 12 months (-0.004 mm), although equivalence was not established at 12 months in an underpowered subgroup (n = 71, all Vietnamese; p = 0.068). Older age-only models under-predicted by 0.07 to 0.12 mm. Published individual prediction intervals were too narrow (coverage 0.77): the means were accurate, the individual uncertainty was not. Indian elongation fell between strata and was matched by no existing model. Conclusions: The models reproduce mean untreated East Asian elongation at 6 months, conditional on cohort independence; South Asian children remain unserved by any existing stratum. The tool is a group-level instrument, not an individual predictor, and a transparent unification of published models in open-source code. Its value for estimating treatment effect awaits back-testing against a trial with a known untreated arm, ideally over 24 to 36 months.

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The Association of Scope of Practice Expansion with Changes in Optometry Workforce Density

Calder, D.; Johnson, T.; Carpenter, C.; Tan, C.; Omotowa, O.; Wu, C.; Singer, P.; Hu, K.; Stagg, B.

2026-08-14 ophthalmology 10.64898/2026.08.12.26360334 medRxiv
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Abstract Importance: Access to eye care is increasingly constrained by declining ophthalmologist workforce density, particularly in rural areas, while optometrist workforce is projected to exceed demand. Numerous state legislatures have expanded optometrist scope of practice (SOP), but the workforce effects of these policies have not been evaluated.. Objective: To evaluate changes in optometrist and ophthalmologist workforce density following state-level expansion of optometrist scope of practice. Design: This retrospective ecological study analyzed workforce density across 50 states and the District of Columbia. Between 2008 - 2019, nine states expanded SOPs for optometrists. We used interrupted time-series regression to estimate associations between these policy changes and provider density from 2010-2021, adjusting for covariates. Setting: Population-based analysis of all 50 US states and the District of Columbia, 2010 - 2021. Participants: State-level workforce data were derived from Bureau of Labor Statistics and US Census data (optometrists) and the American Medical Association Physician Masterfile (ophthalmologists). Socioeconomic covariates were obtained from the American Community Survey. Exposure: State-level legislative expansion of optometrist SOPs to allow injections beyond anti-anaphylaxis treatment, lesion removal, and/or laser procedures. SOP changes were identified through systematic review of legislative and regulatory records. Main Outcomes and Measures: Annual change in optometrist and ophthalmologist workforce density (providers per 100,000 population) following SOP expansion, adjusted for age, income, rates of vision difficulty, diabetes, poverty, and uninsured status. Results: Nine states met inclusion criteria for SOP expansion between 2008 and 2019. Analysis of national data showed that among all 50 US states and the District of Columbia, SOP expansion was associated with a non-significant change in optometrist density (-0.65 per 100,000; 95% CI, -1.87 to 0.57) and ophthalmologist density (+0.09; 95% CI, -0.10 to 0.28). Results were consistent in the 9-state subgroup (optometrists: -0.60, 95% CI -2.90 to 1.70; ophthalmologists: +0.02, 95% CI -0.13 to 0.18). Conclusions and Relevance: Our population-level data suggest that, in the US, state legislation expanding optometrist scope of practice has not been associated with increased workforce density. As numerous state legislatures continue to consider such policies, these findings can inform efforts to balance access to eye care with patient safety.

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Predictors of Visual Acuity, Intraocular Pressure, and Pain in Neovascular Glaucoma: A Mixed-Effects Model and Machine Learning Cohort Analysis

Simons, G. J.; von Fersen, M.; Dahlberg, A.; Vartiainen, V.; Summanen, P.; Harju, M.

2026-08-12 ophthalmology 10.64898/2026.08.11.26360163 medRxiv
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Background/Aims: Neovascular glaucoma (NVG) is a severe, secondary glaucoma. This study aimed to identify factors associated with vision, intraocular pressure (IOP), and ocular pain outcomes. Methods: The cohort included all patients diagnosed with NVG during 2008-2024 at Helsinki University Hospital, Finland. Linear mixed-effects models used pre-specified covariates, whereas machine learning was given the full longitudinal data with biomicroscopic findings as an exploratory approach. Results: 626 patients were analysed. Worse baseline vision and a closed angle were associated with worse follow-up vision. Treatments were associated with lower IOP and less pain rather than better vision. Age, sex and comorbidity were largely not associated with the outcomes. Glaucoma drainage devices showed the greatest initial IOP reduction (-10.2 mmHg, 95% confidence interval, CI -11.9 to -8.6 mmHg), followed by transscleral cyclophotocoagulation (TSCPC, -4.7 mmHg, 95% CI -5.8 to -3.7 mmHg) and peripheral retinal cryotherapy (-2.2 mmHg, 95% CI -3.1 to -1.4 mmHg). TSCPC and cryotherapy were also associated with reduced pain (odds ratio 0.51 and 0.46). Pan-retinal photocoagulation and anti-VEGF showed smaller IOP reductions, with a pain reduction for pan-retinal photocoagulation only. Both methods agreed, and machine learning added no novel clinical findings. Conclusions: Vision in this cohort was largely set by the state of the eye at diagnosis. IOP control and pain relief therefore remain realistic goals even when sight cannot be saved. Peripheral retinal cryotherapy stood out, linked to both lower IOP and less pain, seldom reported in NVG. These associations from a large, unselected cohort identify treatments worth comparing prospectively.

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GLP-1 Receptor Agonist Initiation and Anti-VEGF Treatment Frequency in Diabetic Macular Edema: an IRIS(R) Registry Cohort Study

Nagalamadaka, P.; Ross, C. J.; Gilbert, J. B.; Stillman, H.; Ghauri, S. Y.; Dutton, S. M.; Kearney, W.; Li, J. H.; Leong, A.; Singh, R. P.; Krzystolik, M. G.

2026-08-31 ophthalmology 10.64898/2026.08.29.26361426 medRxiv
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Purpose: To evaluate whether initiation of GLP-1 receptor agonists (GLP-1RAs) is associated with anti-VEGF treatment burden in type 2 diabetes patients with diabetic macular edema (DME) in the IRIS(R) Registry (Intelligent Research in Sight). Methods: Incident GLP-1RA initiators were matched 1:1 with controls via Mahalanobis distance matching (9,896 pairs; N=19,792) on sociodemographics, DME risk factors, and factors influencing GLP-1RA prescription including hypertension, obesity, chronic kidney disease. A longitudinal mixed-effects event-study model evaluated monthly anti-VEGF injection frequency over a 36-month window (12 months before through 24 months after initiation), adjusting for DME duration. Visual acuity (VA) and central subfield thickness (CST) were secondary outcomes. Results: Following GLP-1RA initiation, anti-VEGF injection trajectories did not significantly differ between the matched GLP-1RA and control cohorts (interaction coefficients -0.18 to 1.59, P>0.05). Likewise, no differences in VA were observed between cohorts (-0.05 to 0.04 logMAR, P>0.05) or CST (-14.12 to 33.58 {micro}m, P>0.05). Conclusion: In these matched cohorts, GLP-1RA initiation was not associated with the trajectory of anti-VEGF use or changes in VA or CST. Precis We used the American Academy of Ophthalmology IRIS(R) Registry (Intelligent Research in Sight) to identify patients with DME. In 19,792 matched patients, there was no significant reduction in injection frequency post GLP1-RA initiation and no significant change in VA or CST.

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Tracking Neural, Sensory, and Sensorimotor Adaptation to Progressive Vision Loss in Inherited Retinal Dystrophies: A Multimodal Longitudinal Study Protocol

Verroca, A.; Franchin, E.; Mele, S.; Siviero, I.; Busch, I. M.; Benamati, A.; Sanchez-Lopez, J.; Quisisana, C.; Filosa, A.; Marino, V.; Colombo, L.; Cesari, P.; Rimondini, M.; Dell'Orco, D.; Cecchini, M. P.; Mazzi, C.; Savazzi, S.

2026-08-19 ophthalmology 10.64898/2026.08.18.26360630 medRxiv
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Individuals with inherited retinal dystrophies (IRDs) undergo a slow, genetically heterogeneous loss of vision, yet how the visual cortex and non-visual sensory, motor, and psychological systems adapt to this deprivation remains poorly characterized. Existing evidence comes mainly from single-modality, cross-sectional studies that rarely account for genetic heterogeneity, making it hard to distinguish adaptive change from a direct, non-retinal mutation effect, since several IRD genes are not retina-specific. To address this gap, we designed an observational, longitudinal, multimodal protocol that combines ophthalmological, genetic, and in silico characterization with electrophysiological (steady-state visual evoked potentials and TMS-EEG), chemosensory, sensorimotor, and psycho-personological assessments. Patients aged 18 to 75 years with rod-cone (retinitis pigmentosa, Usher syndrome) or cone and cone-rod dystrophies will be assessed at baseline (T0) and at an 18-month follow-up (T1); sighted controls, matched for age, sex, and handedness, will complete the same battery once. Importantly, pairing genotypic with phenotypic data allows changes in non-visual domains to be interpreted against, rather than independently of, each patient's molecular background. We expect individuals with IRDs to differ from controls in visual cortical responsiveness and in selected non-visual sensory and sensorimotor measures, with genotype-related differences explored where sample size permits. Given the rarity of IRDs, the design is exploratory and emphasizes effect sizes and individual variability over large-sample inference. The protocol was approved by the Ethics Committee of the University of Verona (CARP 08.R1/2024) and follows the Declaration of Helsinki and the GDPR; findings will be disseminated through peer-reviewed publications and shared with patients and IRD patient associations.

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Cataract surgical burden and district level disparities in Bangladesh: A retrospective study

Ahmed, M. S.; Islam, M.; Albert, A.; Jahan, A. F.; Islam, N. L.; Shahnaz, T.; Mahdee, C. M.

2026-08-17 ophthalmology 10.64898/2026.08.15.26360490 medRxiv
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Objective: To describe trends in cataract surgical volume, district-level surgical burden, and early postoperative visual outcomes among patients treated through a multi-district outreach programme in Bangladesh. Methods and Analysis: This retrospective study was conducted using data from patients undergoing cataract surgery through the outreach eye-camp programme of Bashundhara Eye Hospital and Research Institute across eight districts of Bangladesh, between 2016 and 2025 (excluding 2021 because of COVID-19). Annual surgical volume trend was assessed using Poisson regression. Postoperative visual outcome on day 1 was categorized as good, borderline, or poor per WHO criteria. Univariable and multivariable ordinal logistic regression identified predictors of worse outcome. Results: 1,929 cataract-surgery records were included. Surgical volume rose from 34 cases in 2016 to a peak of 677 in 2023 (IRR = 1.20; 95% CI: 1.180, 1.220; p-value< 0.001). Small incision cataract surgery (SICS) was used in 99.43% cases. On postoperative day 1, 70.09% of eyes had a good outcome, 19.44% borderline, and 10.47% poor. Increasing age was independently associated with worse outcome, with 2 to 3 times higher odds among patients over 70. District was independently associated with outcome, with Chapainawabganj and Kushtia having lower odds of worse outcome than Brahmanbaria. Sex was significant only in unadjusted analysis. Conclusion: Surgical volume rose substantially over time. About seven in ten eyes achieved a good outcome on day 1, with age and district as the main predictors of worse outcome. Limitations include a single early assessment, exclusion of incomplete records, no standardized refraction, and unmeasured predictors.

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Ocular diagnostic patterns among patients attending community outreach eye camps in Bangladesh: a retrospective registry-based study

Ahmed, M. S.; Islam, M.; Albert, A.; Jahan, A. F.; Islam, N. L.; Shahnaz, T.; Mahdee, C. M.

2026-08-17 ophthalmology 10.64898/2026.08.15.26360489 medRxiv
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Introduction: Community outreach eye camps extend eye care to underserved rural populations across South Asia, but published data mostly describe surgical yield rather than the full range of presenting conditions. This study described the pattern of ocular diagnoses among patients attending community eye camps in Bangladesh and examined how these patterns varied by year, age, and sex. Methodology: This was a retrospective, registry-based study of patients screened through the outreach eye-camp programme of Bashundhara Eye Hospital and Research Institute, Bangladesh, between 2020 and 2024 (2021 excluded due to COVID-19). Age, sex, and provisional diagnosis were recorded for every patient and grouped into five categories: cataract and lens disorders, refractive errors and presbyopia, ocular surface inflammatory disorders, lacrimal system disorders, and miscellaneous disorders. Multivariable logistic regression models estimated the adjusted odds and predicted prevalence of each diagnostic category by calendar year (adjusted for age group and sex) and by age group and sex (adjusted for calendar year). Results: Among 7,267 patients, refractive errors and presbyopia were the most common category (51.31%), followed by cataract and lens disorders (23.54%), miscellaneous disorders (13.86%), ocular surface inflammatory disorders (8.59%), and lacrimal disorders (2.70%). Ocular surface disorders declined significantly over time (adjusted OR: 0.80/year; p-value<0.001). Cataract showed a borderline decline (adjusted OR: 0.94; p-value=0.065). Cataract prevalence rose steeply with age, from 3-6% below 18 years to 49-55% at 60 and older, while refractive errors/presbyopia peaked at 40-59 years (64-68%) before declining thereafter (30-37%). Ocular surface disorders were most frequent among children. Lacrimal disorders remained uncommon (2-5%), with no significant interaction. Conclusion: Refractive errors and presbyopia were the leading reason for presentation, with distinct age patterns across diagnostic categories. Outreach eye camps should be resourced for both comprehensive refraction, primary eye care and cataract-surgical referral, reflecting actual community-level diagnostic needs.

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Accelerating Functional Endpoints in Geographic Atrophy Trials via Morphology-Based Perimetry Grids

Ometto, G.; Montesano, G.; Binns, A.; Dinah, C.; Crabb, D. P.

2026-08-12 ophthalmology 10.64898/2026.08.10.26360122 medRxiv
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Purpose. To evaluate whether a Geographic Atrophy Morphology-based Mapping Algorithm (GAMMA) grid, informed by geographic atrophy (GA) lesion morphology, can accelerate functional progression detection compared with a conventional 10-2 grid and a dense grid (129 locations). This work is motivated by emerging regulatory expectations requiring at least five locations to worsen by [&ge;]7 dB from baseline. Methods. Binary atrophy masks from six autofluorescence images were used to simulate GA expansion over 3 years at 3-month intervals using a stochastic perimeter-growth model with a fixed preferential expansion direction (Pdir). For each image, 32 independent growth histories and 32 microperimetric test realisations per history were generated. For each grid (10-2, Dense, and GAMMA), 5-point clusters were selected outside the baseline GA lesion along three directions (0{degrees}, 30{degrees}, 120{degrees}) away from Pdir, simulating full, partial, and no prior knowledge of Pdir. Ground-truth sensitivities were <0 dB inside the GA lesion and normal outside, calculated using a published normative equation. Response variability was simulated following Henson et al. with baseline averaging. Detection time was the first visit at which all five selected locations showed [&ge;]7 dB loss from baseline. Survival curves and median detection times (T50) were used to compare grid performance. Results. The GAMMA grid achieved the earliest progression detection across all scenarios. Under full knowledge of the expansion direction, T50 was 1.0 year for GAMMA versus 1.25 and 1.5 years for Dense and 10-2, respectively. With partial knowledge, GAMMA's T50 was 1.25 years versus 1.5 and 2.0 years for Dense and 10-2. Even under no knowledge, GAMMA detected progression earliest (T50 = 1.5 years), while Dense required 6 months longer and 10-2 nearly double the time (2.75 years). Conclusions. The automatic GAMMA grid accelerates detection of localised functional progression compared with conventional and dense grids. Structure-informed grid optimisation may better align testing with likely expansion paths, potentially reducing follow-up duration and sample sizes in perimetry-based interventional trials.

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Effect of iStent inject on unmedicated intraocular pressure in glaucoma: exploratory analysis of clinical trial data

Liu, Z.; Fan Gaskin, J. C.; Ang, G. S.; Bigirimana, D.; Kong, G. Y. X.; Atik, A.; McGuinness, M. B.

2026-08-26 ophthalmology 10.64898/2026.08.23.26361150 medRxiv
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Purpose The direct effect of iStent inject on intraocular pressure (IOP) in patients with glaucoma is difficult to quantify in pragmatic trials where rates of post-surgical IOP-lowering therapy differ between intervention groups. We aimed to quantify the causal effect of iStent inject on unmedicated IOP at 12- and 24-months post-surgery. Methods Adults with mild-to-moderate glaucoma were 1:1 randomised to receive cataract surgery with iStent inject or cataract surgery alone at an Australian hospital (2017-2020, NCT03106181). IOP-lowering medications were prescribed as per clinician discretion. An exploratory analysis was used to estimate the controlled direct effect of iStent inject on IOP, analogous to the effect expected if all participants had undergone medication washout prior to assessment. Results Ninety-five eyes from 80 people were included (67.4% male, mean age 73.0 years, mean baseline IOP 17.1 mmHg). IOP-lowering medication was required for 53% of eyes in each group at 12 months (n=76); at 24 months (n=86) it was required for 43% and 64% in the active and control groups, respectively. Mean IOP was similar between intervention groups at each outcome visit. The controlled direct effect favoured the iStent inject group at 12 months (-2.1-mmHg difference, 95% CI -4.0,-0.3) but was attenuated at 24 months (-0.5 mmHg-difference, 95% CI -2.6,1.6). Conclusion Although the iStent inject was estimated to have an effect on lowering unmedicated IOP at 12 months, this effect had largely disappeared by 24 months. Medication washout is recommended when safe and practical in future trials to estimate these direct effects with more certainty.

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Droplet Digital PCR as a First-Line Detection Tool in the Genetic Diagnosis of Vascular Anomalies

Lane, T.; Green, T. E.; Garza, D.; Brown, N. J.; de Silva, M. G.; Bennett, M. F.; Tubb, C.; Macdonald, S. M. W.; Gascoigne, A.; Phillips, R. J.; Slavin, J.; D'Arcy, C.; MacGregor, D.; Clifford, A.; Pathmanathan, L.; Robertson, S. J.; Bekhor, P.; Simpson, J.; Gooley, S.; Scheffer, I. E.; Berkovic, S. F.; Penington, A. J.; Hildebrand, M.

2026-08-14 genetic and genomic medicine 10.64898/2026.08.11.26359368 medRxiv
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Targeted precision therapies are increasingly used in the treatment of individuals with vascular anomalies (VAs). This increases the need for rapid, accurate and inexpensive genetic diagnosis. Droplet digital polymerase chain reaction (ddPCR) is an alternative to next-generation sequencing (NGS), permitting rapid, highly sensitive interrogation of recurrent pathogenic mosaic variants. We examined the feasibility of ddPCR as a primary diagnostic tool in a large cohort of individuals with VAs. Lesional tissue was collected for ddPCR of up to 46 recurrent pathogenic variants across 16 genes associated with VAs. Specimens were assessed on a subset of assays for each individual based on clinical phenotype. Most individuals who had negative ddPCR results went on to high-depth gene panel or deep exome NGS, or Sanger sequencing. Here we report the phenotypic and molecular findings for 78 newly recruited and tested individuals in addition to the 60 individuals already reported from our cohort. The overall diagnostic yield for our cohort when combined with individuals previously reported was 104/138 (75%). Of 138 individuals tested, recurrent pathogenic variants were detected in 71 (51%) on ddPCR. Variants were most frequently identified in PIK3CA (n=28), TEK (n=18), GNAQ (n=12), or MAP2K1 (n=7). In a further 33 individuals, pathogenic variants were identified on NGS or Sanger sequencing. Our findings indicate that ddPCR is an efficient method achieving a high diagnostic yield in our cohort when used prior to sequencing.

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Prevalence and patterns of ocular injury among patients admitted with head injury at a tertiary referral hospital in Uganda

Oguttu, F.; Olupot, A.; Shiuma, J.; Lyazzi, O. J.; Odong, B.; Jumanne, M. R.; Frank, K.; Nsibirwa, S. G.; Atukunda, I.

2026-08-10 ophthalmology 10.64898/2026.08.06.26359857 medRxiv
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Background Ocular injuries concomitantly occur among patients with head trauma because of the close anatomical relationship between the cranium and the orbit. Unfortunately, they are often overlooked during acute trauma care and may result in preventable visual loss. There is a dearth of data describing the burden and spectrum of ocular injury among head injury patients in sub-Saharan Africa. We conducted a hospital-based cross-sectional study to determine the prevalence and describe the patterns of ocular injury among adults admitted with head injury at the Accidents and Emergency Unit of Mulago National Referral Hospital, Uganda, from 1st May 2025 to 30th July 2025. Methods Consecutive patients aged 18 years and above with a confirmed head injury diagnosis underwent a structured ophthalmic evaluation comprising visual acuity testing, tonometry, slit-lamp and dilated fundus examination, pupillary and ocular motility assessment, confrontation visual fields, and review of craniofacial computed tomography. Ocular injuries were classified by anatomical site and injury type, and the prevalence was reported with a 95% confidence interval. Results Of 383 patients evaluated (mean age 32.7 {+/-} 12.3 years; 89.3% male), road traffic accidents were the leading mechanism of injury (68.9%) and most patients had mild head injury (72.3%). Overall, 268 patients (70.0%; 95% CI 65.1-74.5) sustained at least one ocular injury. Adnexal injuries were most frequent (64.0%), dominated by periorbital oedema (45.2%), subconjunctival haemorrhage (42.3%) and eyelid ecchymosis (33.2%); orbital fractures occurred in 27.4%. Closed and open globe injuries were present in 13.8% and 0.8% of patients, respectively, and abnormal confrontation visual fields in 28.2%. Conclusion Ocular injury is highly prevalent among patients admitted with head injury in this setting, with adnexal and orbital structures most commonly affected. Routine ophthalmic assessment should be integrated into the initial evaluation of all head injury patients to reduce missed injuries and prevent avoidable visual morbidity.

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CHIASM: A Self-Supervised Visual Field Encoder for Neuro-Ophthalmology

Parker, T. M.; Oermann, E. K.; Grossman, S. N.; Kenney, R. C.

2026-08-25 neurology 10.64898/2026.08.23.26361135 medRxiv
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Background: Artificial intelligence (AI) systems for glaucoma diagnosis and prognostication from visual fields (VF) are under active development, yet do not audit for vertical-meridian-respecting field loss - known sequelae of stroke, hemorrhage, and neoplasm. We developed a self-supervised encoder of automated perimetry that learns anatomically interpretable VF structure without labels, and evaluated its capacity to identify suspected neurologic VF patterns in an independent public glaucoma dataset. Methods: We pretrained a 128-dimensional masked autoencoder on 23,223 unlabeled Humphrey VFs (patient-grouped training split of 28,943 fields from 3,871 patients; UWHVF, all-comers perimetry), using monocular pattern-deviation input. A supervised linear classifier over vertical-midline latent dimensions was trained on per-eye expert neurological/non-neurological labels and assessed under hard-negative cross-validation, with specificity evaluated on 100 held-out, structurally separated UWHVF controls. External evaluation used the Harvard-Glaucoma Fairness dataset (Harvard-GF; 3,300 patients with paired VF and optical coherence tomography [OCT] from a single academic center), which contributed no data at any training stage. Results: Masked reconstruction recovered structure concordant with retinal neuroanatomy: 50 of 128 latent dimensions emerged spatially specialized, versus 23 for the total-deviation encoder. The classifier achieved cross-validated balanced accuracy 0.78 (95% CI, 0.75-0.82) and AUC 0.85 (95% CI, 0.82-0.89), with no false positives among the 100 held-out controls. Applied to Harvard-GF without fine-tuning, it identified a top-20 of 1,748 glaucoma-labeled patients (1.1%) with morphology inconsistent with glaucoma; all 20 were positive on the rule-based Neurological Hemifield Test (mean score 62.4), and OCT showed preserved superior (Cohen d = +0.68; P < .001) and inferior (d = +0.63; P = .003) retinal nerve fiber layer versus severity-matched controls. Conclusions: A self-supervised VF encoder learned anatomically interpretable visual field structure from unlabeled data and identified suspected neurological cases in a curated glaucoma dataset, with expert, rule-based, and OCT corroboration. Visual field datasets used to train glaucoma AI may benefit from neurological screening before model training; the encoder reported here supports such audits and provides a foundation for neuro-ophthalmic AI beyond fundus photography and OCT.

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Factors associated with ocular injury among patients admitted with head injury at Mulago National Referral Hospital a tertiary hospital in Uganda

Olupot, A.; Oguttu, F.; Shiuma, J.; Lyazzi, O. J.; Odong, B.; Jumanne, M. R.; Frank, K.; Ntende, J.; Mukunya, D.; Otiti, J. S.; Ampaire, A. M.; Lusobya, R. C.; Nsibirwa, S. G.; Atukunda, I.

2026-08-21 ophthalmology 10.64898/2026.08.18.26360753 medRxiv
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Background Given the close anatomical proximity of the eye and its adnexae to the cranium, ocular injury frequently coexists with head trauma. However, specific factors predisposing patients with head injury to ocular involvement in Uganda remain poorly defined. Objective This study aimed to determine the factors associated with ocular injury among patients with head injury at Mulago National Referral Hospital (MNRH), a tertiary referral facility in Kampala, Uganda. Methods We conducted a cross-sectional study among 383 adult patients admitted with head injury to the Accidents and Emergency Department of MNRH from 15/05/2025 to 30/07/2025. All participants underwent a standardized ophthalmic evaluation. Bivariable and multivariable Poisson regression analyses were used to identify factors associated with ocular injury, reported as adjusted prevalence ratios (APR). Results Ocular injury was identified in 268 of 383 patients (70.0%; 95% CI: 65.1-74.5). On multivariable analysis, age 26-44 years (APR 1.18; 95% CI: 1.11-1.43; p=0.013), commercial motorcyclist (boda-boda rider) occupation (APR 1.25; 95% CI: 1.06-1.47; p=0.007), road traffic accident mechanism of injury (APR 1.19; 95% CI: 1.02-1.38; p=0.03), severe head injury (APR 1.70; 95% CI: 1.44-2.01; p<0.0001), and the presence of facial fractures (APR 1.61; 95% CI: 1.44-1.81; p<0.0001) significantly increased the likelihood of ocular injury. Conversely, intracranial hemorrhagic lesions were inversely associated with ocular injury (APR 0.80; 95% CI: 0.68-0.93; p=0.004). Conclusion Ocular injuries are common among patients with head injury. Patients aged 26 to 44 years, commercial motorcyclist occupation, road traffic injury, severe head injury, and facial fractures have a higher risk of ocular injury. We recommend prioritizing ophthalmic evaluation of for patients admitted with head injury to minimize preventable visual impairment.

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Enhanced Detection of Age-related Macular Degeneration in Low-quality Retinal Images via Noise-Augmented YOLO and Adaptive Attention Mechanisms

Bai, X.; Kishimoto, K.; Sugiyama, O.; TAMURA, H.

2026-08-11 bioinformatics 10.64898/2026.08.04.742925 medRxiv
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This study aims to improve the detection performance of age-related macular degeneration (AMD) in low-quality retinal images. BackgroundAMD is a leading cause of vision loss among older adults globally, and accurate detection is crucial for clinical management. However, low-quality optical coherence tomography (OCT) images significantly compromise diagnostic accuracy. ObjectiveTo enhance AMD detection in low-quality images using noise-augmented data augmentation and an improved YOLO deep learning model. MethodsPublic datasets from UCSD and Duke University were utilized; the training dataset comprised 24,980 OCT images (high-quality and noise-augmented low-quality), while the testing dataset included 1,000 images (584 AMD, 416 normal). The model is based on the YOLOv8n framework, integrated with Squeeze-and-Excitation blocks (SEblock) and Adaptive Sparse Self-Attention (ASSA), with an additional 160x160 detection layer for detecting small lesions. Evaluation metrics included accuracy, sensitivity, specificity, and F2-score. ResultsThe proposed model achieved an accuracy of 99.02%, sensitivity of 98.17%, specificity of 100%, and an F2-score of 98.50% on the Duke dataset. Detection rates were significantly improved compared to traditional methods, particularly in low-quality images, with a detection rate of 89.60%, markedly superior to original YOLOv8n (55.10%) and classical models like ResNet50. ConclusionThe enhanced model, employing noise-augmented training data and improved attention mechanisms, demonstrates excellent AMD detection capabilities in low-quality OCT images, showing broad potential for clinical applications.

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General-purpose time-series foundation models enable sample-efficient transfer learning in retinal electrophysiology

Porter, H. L.; Giles, C. B.; Kottapalli, S.; Wren, J. D.

2026-08-19 ophthalmology 10.64898/2026.08.17.26360646 medRxiv
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Electroretinography (ERG) measures the functional response of distinct retinal cells to light, but was largely displaced by structural imaging in the 2000s. Standardization efforts by the International Society for Clinical Electrophysiology of Vision (ISCEV) began in the late 1980s, and collapsed the rich time-series traces into reproducible components and implicit times. Recent improvements in hardware (RETeval) and software (artificial intelligence) may increase the utility of ERG data. However, no ERG-specific foundation models exist, and there are not enough public datasets to train one. We asked whether time-series foundation models (FMs) trained without ERG-specific pre-training could be adapted through transfer learning. Using two public datasets, PERG-IOBA (pattern ERG with ocular diagnoses), and LEOPs (full-field ERG focusing on Autism Spectrum Disorder, ASD), we interrogated how FMs could improve over smaller within-domain models. We measured the binary (healthy/typically developing vs any annotation) and multiclass (specific family/diagnosis) classification performance of both frozen and fine-tuned FMs, alongside custom autoencoder and multiscale models, using patient-aware splits for cross validation. We benchmark the same architectures against PTB-XL, a large 12-lead ECG corpus, as both a control for each approach and to explore scaling behavior. We show that 1) pre-trained FMs can reconstruct masked traces from all three datasets, 2) frozen and fine-tuned embeddings, especially combined with multimodal metadata through masked autoencoders, performed best on classification tasks. Performance on PTB-XL was maintained down to 300 records, comparable in size to the ERG datasets. We could not reproduce published classification performance on the ASD task. Taken together, these results support general purpose foundation models as a practical approach to ERG analysis.

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Long term use and replacement of near vision glasses for presbyopia, in Punjab, Pakistan: a cross-sectional survey

Moin, M.; Younas, R.; Maqbool, S.; Awan, Z. H.; Bilal, M.; Katibeh, M.; Watts, E.; Latorre-Arteaga, S.; Freels, P. E.; Steinberg, A.; Bastawrous, A.

2026-08-17 ophthalmology 10.64898/2026.08.15.26360501 medRxiv
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Background: An estimated 826 million people have avoidable near vision impairment (NVI) due to lack of access to near vision glasses for presbyopia. Glasses use, uptake and replacement is essential to sustained NVI correction. Here we explore the uptake of second and subsequent pairs of near vision glasses and the willingness to pay. Methods: In this cross-sectional survey, 276 individuals who received near vision glasses through eye health screening programs in Punjab province, Pakistan from 2020 to 2022, were surveyed between February and July 2025, i.e. 3-5 years later. Results: 92.0% (n=254) of respondents were still using near vision glasses: a purchased replacement (41.3%, n=114), a free replacement (30.8%, n=85), or the original pair (19.9%, n=55). Male gender, higher age, and personal income were strongly associated with purchasing additional pairs, while women and those economically dependent on others relied more on free provision (all p values <0.05). Accessibility, indicated by shorter travel times and awareness of supply sources, also played a significant role in sustained replacement. Over 98% of participants expected to obtain (purchase or receive) a new pair of glasses in the future, and over 94% of participants expected to purchase their next pair. The mean willingness-to-pay (WTP) was 353 PKR (95% CI: 327-379) // 1.25 USD (95% CI: 1.16-1.34), while the average reported price paid was 416.67 PKR // 1.47 USD (95% CI: 351.39-481.94)). Conclusion: Sustained use of near vision glasses remained high 3-5 years after initial provision. Many recipients had purchased replacements, and willingness and ability to pay were high among participants, suggesting potential for sustained demand beyond initial subsidized distribution.

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Multi-biobank genome-wide association study of dermatochalasis implicates genes involved in skin biology and morphology

Rajueni, K.; Koskimaki, F.; Salo, V.; Pasanen, A.; Sliz, E.; Vanhala, S.; Reis, K.; Reigo, A.; FinnGen, ; Estonian Biobank Research Team, ; Palta, P.; Tasanen, K.; Liinamaa, J.; Kettunen, J.; Saarela, V.; Karjalainen, M. K.

2026-08-06 ophthalmology 10.64898/2026.08.04.26359692 medRxiv
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Objective: The objective of this study was to detect genetic factors associated with dermatochalasis using a genome-wide association study (GWAS) across three large cohorts. Design: GWAS meta-analysis Participants: A total of 13,200 dermatochalasis cases and 962,513 controls were included. Methods: A GWAS meta-analysis of dermatochalasis combining data from the FinnGen, the Estonian Biobank and the UK Biobank was conducted. We also performed colocalization analyses, a phenome-wide association study and age-at-onset analysis, and assessed genetic correlations with various diseases and traits. Main outcome measures: Identification of genetic variants associated with dermatochalasis. Results: We identified 18 loci associated with dermatochalasis at genome-wide significance, 16 of which were novel. Most of these loci had genes involved in skin biology and cutaneous diseases, such as the genes encoding elastin (ELN) and Latent TGF-{beta} binding protein 1 (LTBP1). Phenome-wide association study revealed previous associations with morphology-related traits, while genetic correlation analysis highlighted multiple genetic correlations, especially with smoking and pain. Conclusions: We detected 18 genetic loci associated with dermatochalasis, characterized these loci in detail and demonstrated their relevance in skin biology and related processes. These findings give novel information on the genetic background of dermatochalasis and provide a solid basis for further research.

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Targeting Mitochondrial Dysfunction with Mdivi-1 Confers Therapeutic Protection in a Mouse Model of Mustard Keratopathy

Guha Mazumder, A.; Magarychoff, E.; Alemi, H.; Raghav, R.; Chin, M. T.; Wiley, C. D.; Fini, M. E.

2026-08-28 biochemistry 10.64898/2026.08.27.742467 medRxiv
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Mustard keratopathy, caused by exposure of the cornea to sulfur or nitrogen mustard vesicants, chemical warfare agents, can lead to severe and often irreversible vision loss. Despite considerable efforts to develop medical countermeasures, including anti-inflammatory, antioxidant, anti-fibrotic, and anti-angiogenic therapies, no treatment effectively targets the underlying mechanisms responsible for mustard-induced tissue injury or prevents long-term disease progression. In the present study, we comprehensively define mitochondrial mechanisms underlying nitrogen mustard-induced corneal injury in both our cell culture model in vitro and a mouse model in vivo. DNM1L (aka Drp1) is a mitochondria-localized dynamin-related GTPase that executes mitochondrial fission and facilitates the autophagic elimination of damaged mitochondrial components. Using complementary in vitro and in vivo models, we demonstrate that nitrogen mustard rapidly induces excessive mitochondrial fragmentation, bioenergetic collapse, membrane depolarization, oxidative stress, intracellular acidification, mitophagy, and apoptotic cell death. Pharmacological inhibition of DNM1L with Mdivi-1 preserves mitochondrial structure and function, restores cellular metabolism, reduces oxidative damage, and markedly improves corneal epithelial integrity, and tissue repair following nitrogen mustard exposure. Collectively, these findings establish mitochondrial dysfunction as a central pathological mechanism in mustard keratopathy and identify DNM1L-mediated mitochondrial remodeling as a therapeutically actionable target. Our work provides strong preclinical evidence supporting mitochondrial-directed therapy as a promising strategy for treating mustard keratopathy.