British Journal of Ophthalmology

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.

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.

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.

Purpose: To characterize the biomechanical response of the optic nerve head (ONH) in myopic versus non-myopic individuals with normal-tension glaucoma (NTG), and to evaluate the association between ONH strains and the rate of visual field (VF) progression. Design: Retrospective clinical cohort study. Participants: A total of 118 NTG eyes from 77 patients with [&ge;] 2 years of follow-up and 5 VF tests were enrolled, including 66 eyes with myopia and 52 eyes without. Methods: Each participant underwent three-dimensional (3D) optical coherence tomography (OCT) imaging of the ONH under three mechanical loading conditions: 20{degrees} adduction, 30{degrees} abduction and acute intraocular pressure (IOP) elevation by applying a 0.80 N force to the lower eyelid. Effective strains across the global ONH complex and within specific segmented tissues (pre-lamina, lamina cribrosa, choroid, and sclera) were quantified using a validated 3D strain-mapping algorithm. Results: Myopic NTG eyes exhibited significantly higher ONH strains compared to non-myopic eyes under acute IOP elevation (10.1{+/-}2.7% vs. 9.3{+/-}1.8%, P = 0.044) and abduction (9.2{+/-}2.3% vs. 8.4{+/-}2.1%, P = 0.048). In the non-myopic group, ONH strains varied significantly across conditions (P < 0.001), with adduction (9.9{+/-}2.0%) and acute IOP elevation (9.3{+/-}1.8%) eliciting greater strains than abduction (8.4{+/-}2.1%). These condition-dependent variations were less pronounced in the myopic group (10.1{+/-}2.7% vs. 9.8{+/-}2.7% vs. 9.2{+/-}2.3%, P = 0.07). Multivariable linear mixed-effects analysis revealed that in myopic NTG, higher ONH strains induced by adduction were significantly associated with faster MD decline (estimate: -0.139 dB/year per 1% increase, P = 0.03, adjusted for age, spherical equivalent and baseline perimetric mean defect). Conversely, larger strains during acute IOP elevation were associated with slower progression (estimate: 0.184 dB/year per 1% increase, P = 0.004). Tissue-specific analysis confirmed that adduction-induced strains in the choroid and pre-lamina tissue as well as IOP-induced strains across all ONH tissues were significantly correlated with the rate of perimetric progression in myopic eyes (all P < 0.05). Conclusions: In this cohort, greater adduction-induced ONH strain was associated with faster perimetric deterioration in myopic NTG. These findings support further investigation of gaze-related optic nerve traction as a potential non-IOP-related biomechanical factor in myopic NTG. Keywords: Normal tension glaucoma, Myopia, Optic nerve head, Ocular biomechanics, Visual field Progression, adduction.

Published artificial intelligence for keratoconus is unproven in fellow eyes that topography and tomography call normal, the eyes where surgical decisions are made, although it reports near-perfect accuracy for early disease. In a registered systematic review of 573 studies (PROSPERO CRD420261441197), none of 2,035 claim-by-stratum units from 212 adjudicated studies established discrimination in these eyes. Most units (90.0%) answered a different question, never constructed the target population or certified its normality; external validation did not test label generation, and five systematic reviews did not assess it. In a public cohort, a frozen score yielded an area under the receiver operating characteristic curve of 0.996 against a same-eye index label and 0.549 against a contralateral proxy; its inputs reconstructed the label-generating index (r = 0.991), so accuracy there measured agreement with the index. Anchor-gap evaluation measures accuracy in these eyes against the contralateral clinical diagnosis.

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

Abstract Purpose To apply a mathematical model integrating vascular permeability, lesion transmural pressure, choroidal excess pressure, and wall stability to incomplete fluid response and massive submacular hemorrhage in neovascular age-related macular degeneration. Methods Permeability was calculated from aqueous vascular endothelial growth factor (VEGF). Windkessel gave usual lesion pressure from choriocapillaris pressure and high inflow from an arterial-level puncture pressure used as a working value. Choroidal excess pressure was calculated from choroidal thickness and a pachy index as increased outflow resistance. Exudative change used a revised Starling equation scaled to early central-retinal-thickness reduction, with 40-m threshold. A relative rupture-hazard index was calculated from Laplace wall stress and wall stability. VEGF, pressures, and that reduction were from the literature. Pressure was isolated from permeability and choroidal excess. Results In the model, raising lesion pressure from choroidal-excess lesion pressure to high inflow increased untreated exudative change from 150 to 760 m. Residual under saturation was 64 m as a lower-end reference (Monte Carlo 69 - 286 m; median, 170) and 90 m with high-hazard choroidal excess; both above 40 m. Reducing choroidal thickness in the thickened choroidal-excess state added 13 - 14 m, smaller than that residual. Lowering lesion pressure from high inflow to usual lesion pressure (21 to 10 mmHg) reduced the index to 0.64 of the high-hazard reference, and to 0.34 with wall stabilization. Conclusion Lesion transmural pressure due to high inflow left residual exudation even after permeability suppression with anti-VEGF. Fluid resolution on optical coherence tomography may not parallel a reduction in the rupture-hazard index, depending on wall stability.

Purpose: To evaluate the associations of the numerical AI-CO center index and visually classified central dark-area extent with Humphrey 10-2 mean deviation (MD). Methods: This single-center retrospective study included 320 eyes of 169 patients with AI-CO imaging, broad-field 24-2F or 30-2 testing, and 10-2 testing. Both visual field examinations were performed within 365 days before or after AI-CO imaging. Two ophthalmologists independently classified central dark-area extent into five Levels (0-4). Analyses assessed Spearman correlations, areas under the receiver operating characteristic curve (AUCs), distributions across final central dark-area Levels, and interrater reliability. Patient-cluster bootstrap confidence intervals and a one-eye-per-patient sensitivity analysis addressed inclusion of both eyes. Results: AI-CO center correlated with 10-2 MD (rho=0.829; 95% CI, 0.773-0.873). AUCs for 10-2 MD below -2, -6, and -12 dB were 0.902, 0.939, and 0.961, respectively. The numbers of eyes in Levels 0-4 were 66, 57, 94, 53, and 50; median 10-2 MD values were -0.59, -1.48, -3.54, -6.24, and -18.15 dB, respectively. Quadratic-weighted kappa was 0.970 (95% CI, 0.958-0.981). Sensitivity analyses yielded broadly similar findings. Conclusions: The numerical AI-CO center index and visually classified central dark-area extent were associated with central visual field damage. Assessing the extent of dark regions in the central image alongside the numerical index may provide useful information for interpreting central visual field status from the AI-CO display.

Iris biomechanics plays a key role in primary angle-closure glaucoma (PACG). Soft tissue biomechanics is heavily influenced by tissue water content; therefore, accurately assessing water content is needed to describe iris biomechanics in a physiologically relevant manner. Yet, accurate experimental measurements of iris water content are rare in the literature. Therefore, our objective was to experimentally assess iris water content and potential sex differences in New Zealand White rabbit iris--a suitable model for studying iris biomechanics. We also examined the effect of exposure to phosphate-buffered saline (PBS) on iris water content, given its common use to maintain hydration during soft-tissue biomechanical testing. Our results showed slightly higher water content in males (89.2% {+/-} 2.3%) than in females (87.7% {+/-} 2.2%) (p = 0.022), while we found no significant differences in gross iris morphology between the sexes, indicating subtle compositional differences. Furthermore, PBS incubation had a minimal effect on water content only in female irides. Overall, our results indicated high iris water content in both sexes compared with anatomically adjacent ocular tissues and other soft connective tissues. These results improve our understanding of iris composition and physiology and can serve as a baseline for constructing biomechanical models to assess its role in PACG.

Abstract Purpose: To use a minimally invasive lid treatment (MILT) utilizing Compressive Skin Contouring (CoCo) technology to compare patient- and surgeon-reported ecchymosis, edema, and incision appearance following MILT and traditional upper eyelid blepharoplasty (tBULB). Methods: Prospective, single-surgeon intra-patient study comparing MILT and tBULB in patients seen for bilateral blepharoplasty. Patients and the operating surgeon rated MILT and tBULB outcomes post-operatively on the day of surgery (T1) and at 2 months (T2) using surveys. Patient photographs taken 3 and 9 days post-operatively were blindly assessed by 3 independent surgeons to compare ecchymosis, edema, and incision appearance on the MILT and tBULB sides. Results: Seven patients participated in the study. At T1, 6/7 patients reported [&le;] ecchymosis and edema, and all patients reported better or equivalent incision appearance on the MILT side compared to the tBULB side. At T2, 6/7 of patients reported [&le;] edema; 4/7 reported < ecchymosis and better incision appearance on the MILT side. The surgeon reported < ecchymosis and [&le;] edema for 7/7 patients and better or equivalent incision appearance for 6/7 patients at T1; [&le;] ecchymosis and better or equivalent incision appearance for 7/7 and [&le;] edema for 6/7 patients at T2 on the MILT side. In the blinded evaluation, mean ecchymosis scores were lower, edema scores were lower or equivalent, and incision appearance was better for MILT vs. tBULB at days 3 and 9. Conclusions: In this intra-patient study, MILT outcomes compared favorably with tBULB, especially for ecchymosis and edema; two important aesthetic measures of patient perception.

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.

Purpose: To develop an interpretable automated pipeline for dome-shaped macula (DSM) detection and measurement from optical coherence tomography (OCT) B-scans. Methods: We analyzed one eye from each of 300 children aged 4-18 years in the Shanghai Child and Adolescent Large-scale Eye Study High Myopia (SCALE-HM) cohort (50 DSM-positive; 100 test eyes). A U-Net pretrained on OCTA-500 and fine-tuned on the development set segmented the retinal pigment epithelium (RPE) boundary. A geometric module located the apex, fitted a tangent-line baseline, and computed perpendicular height in physical coordinates. An eye was DSM-positive if any gradable B-scan had height >= 50 um. Two masked graders evaluated the test set; a third adjudicated disagreements. Results: The area under the receiver operating characteristic curve was 0.927 (95% confidence interval [CI], 0.850-0.986), sensitivity was 82.1% (95% CI, 64.4%-92.1%), and specificity was 100% (95% CI, 94.9%-100%) against the adjudicated reference. In concordant-positive eyes, automated height agreed with manual measurements (intraclass correlation coefficient, 0.949; mean absolute error, 6.9 um; bias, -5.7 um, versus Doctor A). Mean RPE-boundary error on pediatric test scans was 1.54 um. Conclusions: The pipeline may be considered a reliable and reproducible tool for automated DSM detection and height measurement on radial OCT, with each value traceable to landmarks on the source B-scan. External validation across populations, devices, and acquisition protocols is needed. Translational Relevance: The pipeline provides an objective and reproducible method to detect DSM and quantify dome height, width, and orientation across OCT meridians. Because each measurement can be verified on the source B-scan, it enables standardized DSM assessment.

Purpose: To externally evaluate the real-world performance of a commercially implemented artificial intelligence system that analyzes OCT image data and provides numerical and grayscale reference outputs, by characterizing the association and numerical relationship between AI-CO output and Humphrey visual field mean deviation (MD) in routine clinical practice. Study Design: Retrospective, single-center observational study. Methods: This study included 819 eyes of 424 patients who underwent AI-CO analysis and Humphrey 24-2F or 30-2 visual field testing within 1 year. The 24-2F and 30-2 groups comprised 343 and 476 eyes, respectively. Because the AI-CO all value, corresponding to the index labeled "peripheral" in the Japanese user interface, is a unitless index, its numerical relationship with Humphrey MD was explored using Pearson correlation, Bland-Altman analysis, and Passing-Bablok regression. Linearity was assessed using the original cumulative sum (CUSUM) procedure described by Passing and Bablok. Results: The AI-CO all value was strongly correlated with Humphrey MD in both the 24-2F (r = 0.836) and 30-2 (r = 0.854) groups (both P < 0.001). In Bland-Altman analysis, the mean difference (AI-CO all minus Humphrey MD) and 95% limits of agreement were -1.23 (-7.23 to 4.77) in the 24-2F group and -1.44 (-7.96 to 5.08) in the 30-2 group. In both groups, the 95% confidence interval for the Passing-Bablok slope included 1, whereas that for the intercept excluded 0. The original CUSUM procedure did not reject linearity in the overall cohort, the 24-2F group, or the 30-2 group (P = 0.086, 0.091, and 0.145, respectively). Conclusions: In this independent real-world external evaluation of a clinically implemented system, AI-CO all was strongly correlated with Humphrey MD, and linearity of their numerical relationship was not rejected. However, its unitless output was lower on average and showed substantial eye-level variability. AI-CO may therefore provide complementary structural-functional information in routine care but should not be interpreted as interchangeable with standard automated perimetry.

Diabetic retinopathy (DR) screening commonly relies on fixed follow-up intervals, although progression risk differs across patients. We developed a preliminary image-clinical framework to support personalized follow-up recommendations from retinal fundus images and systemic risk factors. Public DR datasets were harmonized into a binary task distinguishing absence of DR from DR of any grade. An ImageNet-pretrained ResNet50 and a foundation model-based feature extraction pipeline were compared. The selected image model was integrated with literature-derived severe retinopathy progression curves and clinical risk modifiers to estimate personalized cumulative risk and assign follow-up intervals using a predefined acceptable risk threshold. The ResNet50-based model was selected for subsequent analyses. In the target cohort, the integrated model assigned 90.0\% of patients to follow-up within 12 months. Clinical adjustment substantially modified image-only recommendations, generally shifting patients toward shorter intervals. These preliminary findings support the feasibility of combining image-derived estimates of baseline DR status with clinical modifiers to inform personalized screening intervals. Larger longitudinal studies are needed to validate calibration, clinical utility, and safety before real-world implementation.

Purpose Device-specific field-of-view (FOV) may affect quantitative optical coherence tomography angiography (OCTA) metrics. This study quantifies inter-device FOV scale differences across four commonly used clinical OCTA devices. Methods Four devices were evaluated under a nominal 6 by 6 mm (or 20 degrees by 20 degrees) scanning protocol: Zeiss Cirrus, Heidelberg Spectralis, Topcon Triton, and Topcon Maestro2. Device-specific spatial scale was assessed by (1) phantom calibration using a model eye with a 1 by 1 mm checkerboard, computing scale factors relative to Zeiss Cirrus; and (2) in vivo validation, registering same-eye, same-visit retinal images from the three devices to those of Zeiss Cirrus and extracting scale factors from the transformation matrices. Correlation between DICOM-implied FOV and spherical equivalent (SE) was assessed, where DICOM-implied FOV equals pixel-spacing mutiply by image-dimension. Results Phantom measurements showed that Spectralis, Triton, and Maestro2 each captured a systematically smaller FOV than Cirrus, with geometric mean scale factors of 0.933, 0.954, and 0.967. The same pattern was observed across 801 eyes from 556 participants, giving geometric mean scale factors of 0.939, 0.943, and 0.960, agreeing with phantom estimates within 1.2%. DICOM-implied FOV was fixed at 6.000 by 6.000 mm for three devices but varied from 5.212 by 5.209 to 6.743 by 6.739 mm for Spectralis, correlating with SE (P < 0.001). Conclusion Systematic FOV discrepancies exist across clinical OCTA devices despite nominally identical protocols, and DICOM pixel-spacing should be interpreted with caution as a spatial measure. Translational Relevance The reported device-specific scale factors could serve as magnification corrections for quantitative OCTA metrics, addressing the systematic spatial inter-device discrepancies.

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.

Purpose To evaluate the safety, tolerability, and preliminary bioactivity of a single suprachoroidal injection of AXT107 (Gersizangitide), a multimodal integrin-disrupting peptide that acts on both the VEGFA pathway and angiopoietin-Tie2 pathway, in eyes with neovascular age-related macular degeneration (nAMD). Design Phase 1/2a, open-label, dose-escalation clinical trial. Participants Fifteen subjects with active nAMD, including 11 treatment-experienced partial responders to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and 4 treatment-naive subjects; 14 eyes met the protocol-specified baseline imaging criterion and were included in efficacy analyses. Methods Study eyes received a single suprachoroidal injection of AXT107 microparticles at doses of 0.125, 0.25, or 0.5 mg and were followed for 40 weeks. Protocol-specified rescue intravitreal anti-VEGF treatment was permitted from week 12 based on protocol-specified best-corrected visual acuity (BCVA) or central subfield thickness (CST) criteria; anti-VEGF treatment before Week 12 was investigator-initiated. Primary outcomes were ocular and systemic safety through week 40; secondary outcomes included change in CST, change in BCVA, and time to first protocol-specified rescue injection. Main Outcome Measures Incidence of ocular and systemic adverse events, intraocular pressure (IOP), CST, BCVA, and time to first protocol-specified rescue injection. Results Twenty subjects were screened and 15 enrolled across 4 U.S. sites; 3 eyes received 0.125 mg, 3 received 0.25 mg, and 9 received 0.5 mg of AXT107. No serious adverse events related to AXT107 occurred, and no cases of endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or clinically significant intraocular inflammation were observed through week 40. No clinically meaningful intraocular pressure (IOP) elevations occurred at any dose, and no subject required chronic IOP-lowering therapy. Among the 14 eligible eyes included in efficacy analyses, 2 eyes (01-04 and 01-05) completed 40 weeks without protocol-specified anti-VEGF rescue, and 1 eye (02-04) first received protocol-specified rescue at week 36. At the last on-treatment visit, BCVA changes ranged from +15 to -31 ETDRS letters; 3 eyes gained[&ge;]5 letters, 3 gained[&ge;]10 letters, and 1 gained[&ge;]15 letters. Among the 14 eligible eyes, anatomical improvements in CST were observed in at least 1 eye in each dose cohort. The most durable responses were seen in treatment-experienced eyes receiving 0.5 mg (median durability of 36 weeks), whereas treatment-naive 0.5-mg eyes showed more variable courses and generally earlier protocol-specified rescue in this small cohort. Conclusions In this first-in-human study, a single suprachoroidal injection of AXT107 up to 0.5 mg was well tolerated through Week 40, with no drug-related serious adverse events, no clinically significant intraocular inflammation, and no sustained IOP elevations. After a single suprachoroidal AXT107 injection, 2 eyes completed 40 weeks without protocol-specified rescue anti-VEGF treatment, and 1 additional eye received its first protocol-specified rescue treatment at Week 36. The exploratory observation that durability appeared greatest in treatment-experienced eyes supports further controlled study of AXT107, particularly in treatment-experienced nAMD populations.

Glaucoma is a leading cause of irreversible blindness worldwide. Ophthalmologists diagnose glaucoma through a structured reasoning process by sequentially evaluating optic nerve head characteristics before reaching a final diagnosis, whereas existing AI systems typically perform direct image classification without providing clinically meaningful reasoning. We present the first clinically annotated fundus reasoning dataset, comprising 1,077 fundus photographs paired with expert-authored six-step diagnostic reports. Building on this dataset, we develop a reasoning-driven vision-language framework that explicitly models the ophthalmologist's diagnostic workflow by generating structured clinical reasoning prior to diagnosis. The generated reports are clinically validated, achieving the best performance across all evaluated clinical findings, including a cup-to-disc ratio mean absolute error of 0.070, an ISNT Kendall distance of 1.73, and the highest semantic agreement with expert reports (BERTScore-F1 = 0.874). The resulting framework also improves glaucoma diagnosis, achieving a balanced accuracy of $94.7\%$ and precision of $94.8\%$, demonstrating that explicitly modeling expert clinical reasoning simultaneously improves interpretability and diagnostic performance. Code and data are available at \url{https://glaucoma-cot.github.io/}.

Introduction: Contact lens (CL) use is increasing globally, yet epidemiological data on CL wearers remain limited in Southeast Asia, including Indonesia. This study aimed to describe the demographic characteristics of CL users, the distribution of CL types, and the factors associated with CL wear patterns and correction status in Indonesia. Methods: This cross-sectional study used convenience sampling to recruit current CL users aged 18-40 years through online advertisements and an ophthalmology clinic in Indonesia. Participants self-reported demographic data, CL type, reasons for use, and refractive correction details. Associations between categorical variables were assessed using chi-square or Fisher's exact tests. Agreement between recommended and actual CL spherical power was evaluated using the Wilcoxon signed-rank test, and factors associated with correction status were analyzed using multinomial logistic regression. Results: Among 350 participants, the majority were female (95.4%), aged 18-30 years (54.0%), held a bachelor's degree (66.6%), and earned [&ge;]Rp5,000,000 monthly (64.9%). Soft colored lenses were the most commonly used type (60.1%), and practicality was the most frequently cited reason for use (38.1%), followed by cosmetic purposes (31.1%) and refractive correction (30.8%). Mild myopia was the most prevalent refractive error (40.0%). Undercorrection was the most common CL correction status (44.4% OD, 44.8% OS), with actual CL power significantly less negative than the recommended power in both eyes (OD: -0.18 D, p=0.015; OS: -0.24 D, p=0.001). Greater myopia severity was significantly associated with both undercorrection (OR 3.63-5.01) and overcorrection (OR 4.22-5.83) in both eyes (all p<0.001), while age, wear duration, and sex showed no significant association. Conclusion: This first nationwide demographic study of CL wearers in Indonesia found a predominance of colored soft lenses and a substantial tendency toward undercorrection linked to myopia severity. These findings highlight the need for public education on professional CL fitting, prescribing, and safe use practices.

Purpose: To understand the functional impact of macular atrophy (MA) and fibrosis in eyes with treated neovascular age-related macular degeneration (nAMD) based on deep visual sensitivity losses. Design: Cross-sectional study. Participants: One-hundred and nine eyes from 97 individuals with nAMD that had been treated for >=12 months without significant retinal fluid. Methods: All participants underwent defect-mapping microperimetry (DMP) testing - a strategy optimized to quantify the spatial extent of deep visual sensitivity losses through single 10 decibel stimuli presentations - where 208 locations were sampled in the central 8 degrees radius region. Participants also underwent color fundus photography, fundus autofluorescence and OCT imaging, which were co-registered and manually annotated for MA and fibrosis to determine their two-dimensional pointwise extent at individual test locations, and global extent in the corresponding region where DMP was performed. Main Outcome Measures: Pointwise association between the presence of MA and fibrosis with missing a stimulus on DMP and global association between the extent of MA and fibrosis with the proportion of locations missed (PLM) on DMP. Results: At a pointwise level, the presence of MA and fibrosis were independently associated with an increased likelihood of missing a stimulus on DMP (odds ratio = 42.5 and 2.5 respectively; P < 0.001 for both). However, at a global level, only an increasing extent of MA was associated with a significantly higher PLM on DMP (P < 0.001), but not fibrosis (P <= 0.227). MA extent explained a substantial proportion of the variance in the PLM (R2 = 0.97) and there was a very strong correlation between the two parameters ({rho} = 0.93). Conclusions: This study confirmed the expected functional impact of MA and fibrosis on DMP testing at a pointwise level. However, it showed at the global level that only the extent of MA, and not fibrosis, was independently associated with functional loss on DMP, and that there was a very strong structure-function correlation based on MA. These findings thus suggest that evaluating MA alone may be sufficient for capturing structural changes strongly associated with the global extent of deep visual sensitivity losses in those with treated nAMD.