Ophthalmology science最新文献

{"title":"Interactions Between Epidermal Growth Factor–Containing Fibulin-Like Extracellular Matrix Protein 1 and Tissue Inhibitor of Metalloproteinases-3 and Relevance to Age-Related Macular Degeneration","authors":"Clara Ehrenzeller MD,&nbsp;Robert E. MacLaren MD, PhD","doi":"10.1016/j.xops.2026.101287","DOIUrl":"10.1016/j.xops.2026.101287","url":null,"abstract":"<div><h3>Clinical Relevance</h3><div>Age-related macular degeneration (AMD) remains the leading cause of irreversible blindness in Western populations, with no approved therapies for the dry form characterized by drusen accumulation and retinal pigment epithelium atrophy. This review examines extracellular matrix alterations in Bruch's membrane by comparing healthy aging, AMD pathogenesis, and Doyne Honeycomb Retinal Dystrophy—a monogenic disorder that serves as a surrogate model for AMD due to similar phenotypic manifestations.</div></div><div><h3>Methods</h3><div>We focus on the critical interactions between epidermal growth factor–containing fibulin-like extracellular matrix protein 1 (EFEMP1), matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases-3, and complement factors. We explore their roles in extracellular matrix homeostasis disruption. In healthy aging, oxidative stress and inefficient waste removal drive gradual matrix remodeling and low-grade inflammation. Age-related macular degeneration results from polygenic risk variants in complement and extracellular matrix genes, combined with environmental stressors, leading to accelerated matrix dysfunction and chronic complement activation. In Doyne Honeycomb Retinal Dystrophy, the EFEMP1 R345W mutation causes rapid disease progression through impaired protein secretion, abnormal matrix accumulation, and complement dysregulation.</div></div><div><h3>Results</h3><div>Our analysis reveals that EFEMP1–tissue inhibitor of metalloproteinases-3 complexation may represent a critical threshold in drusen formation across both conditions, AMD and Doyne Honeycomb Retinal Dystrophy.</div></div><div><h3>Conclusion</h3><div>While AMD pathogenesis unfolds over decades through cumulative insults, the EFEMP1 mutation compresses similar pathological changes into 30 to 40 years, suggesting this mutation acts as a major hazard for matrix homeostasis disruption. Understanding these shared mechanisms provides insights into therapeutic targets, including complement inhibition, MMP modulation, and EFEMP1-directed interventions. We propose continued investigation of Doyne Honeycomb Retinal Dystrophy as a valuable model for identifying AMD treatments.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 8","pages":"Article 101287"},"PeriodicalIF":5.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148657402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus Guidance for Screening, Classification, and Treatment of Retinopathy Associated with Incontinentia Pigmenti","authors":"Jade Y. Moon MD,&nbsp;Becky Abbott MPH,&nbsp;Audina Berrocal MD,&nbsp;Connie Chen MD,&nbsp;Xi Chen MD,&nbsp;Philip Ferrone MD,&nbsp;Mary Fete MSN, RN,&nbsp;Morton F. Goldberg MD,&nbsp;Dorothy K. Grange MD,&nbsp;Ian Han MD,&nbsp;M. Elizabeth Hartnett MD,&nbsp;Robert H. Henderson MD,&nbsp;Eric Nudleman MD,&nbsp;Sengul Ozdek MD, FASRS,&nbsp;Richard N. Sather III MD,&nbsp;Nicole Somani MD, MPH,&nbsp;Reid Wilson MD, PhD,&nbsp;Sandra R. Montezuma MD,&nbsp;J. Peter Campbell MD, MPH","doi":"10.1016/j.xops.2026.101293","DOIUrl":"10.1016/j.xops.2026.101293","url":null,"abstract":"<div><h3>Objective</h3><div>Incontinentia pigmenti (IP) is a rare genetic condition that can lead to blindness. Clinical practice for screening for the ocular complications of IP is variable. Current literature lacks consensus for the screening, classification, and treatment of IP-related eye disease despite substantial risk of retinal detachment (RD) and blindness. This report summarizes the state of knowledge and establishes expert guidance for screening, classification, and treatment of IP-related eye disease from the International Conference on Incontinentia Pigmenti (ICIP) sponsored by the National Foundation for Ectodermal Dysplasias in February 2025.</div></div><div><h3>Design</h3><div>Literature review.</div></div><div><h3>Subjects</h3><div>Images from authors' patients with a diagnosis of IP were included in this study.</div></div><div><h3>Methods</h3><div>We review the current literature on screening and treatment of retinal complications of IP and provide guidance on disease screening, classification, and management from the ICIP in 2025.</div></div><div><h3>Main Outcome Measures</h3><div>Screening, treatment, and surveillance options were reviewed.</div></div><div><h3>Results</h3><div>The ICIP established guidance to support parents and ophthalmologists in appropriate screening and treatment of infants diagnosed with IP. Due to the high prevalence of retinal involvement in IP, infants diagnosed with IP should receive an early, comprehensive retinal examination, ideally with widefield fluorescein angiography. Like treatment considerations for other pediatric diseases with retinal ischemia, treatment concentrates acutely on regression of neovascularization and strategies to reduce incidence of RDs later in life.</div></div><div><h3>Conclusions</h3><div>Incontinentia pigmenti is a rare but complex multisystem disorder with the potential for serious retinal complications. Careful ophthalmic screening and surveillance are crucial to optimize patients' visual outcomes.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 8","pages":"Article 101293"},"PeriodicalIF":5.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Spontaneous Brain Activity in Adolescents and Adults with Comitant Strabismus and Strabismic Amblyopia","authors":"Yiru Huang PhD,&nbsp;Zitian Liu PhD,&nbsp;Yanyan Wu PhD,&nbsp;Daming Deng MM,&nbsp;Minbin Yu MD, PhD","doi":"10.1016/j.xops.2026.101290","DOIUrl":"10.1016/j.xops.2026.101290","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Neuroimaging studies have established that strabismus and amblyopia are associated with structural and functional brain alterations. However, differences in spontaneous brain activity between strabismus patients with and without amblyopia remain unclear. This study employed fractional amplitude of low-frequency fluctuation (fALFF), a normalized version of the amplitude of low-frequency fluctuation that reduces physiological noise and improves detection of spontaneous brain activity, to examine spontaneous brain activity patterns in comitant strabismus (CS) and strabismic amblyopia (SA) patients in adolescents and adults.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Cross-sectional study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;Seventeen patients with CS (10 males and 7 females; mean age, 24.41 ± 6.70 years), 19 patients with SA (9 males and 10 females; mean age, 24.53 ± 6.12 years), and 22 normal controls (12 males and 10 females; mean age, 22.29 ± 3.93 years) were recruited.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Resting-state functional magnetic resonance imaging was performed.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Spontaneous brain activity was assessed using fALFF. Pearson correlation analysis was employed to examine the relationships between fALFF values in altered brain regions and clinical manifestations. Additionally, receiver operating characteristic curve analysis was conducted to descriptively evaluate the discriminatory capacity of fALFF signals between SA and CS patients in this exploratory sample.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Compared with normal controls, both CS and SA patients showed widespread fALFF alterations in visual, sensorimotor, and higher-order cognitive regions. Relative to CS patients, SA patients showed reduced fALFF in the bilateral frontal lobes and elevated fALFF in the left precentral gyrus. An exploratory analysis revealed that fALFF values in the left middle frontal gyrus of SA patients were negatively correlated with the best-corrected visual acuity of the amblyopic eye (r = –0.49, nominal &lt;em&gt;P&lt;/em&gt; = 0.033). Receiver operating characteristic analysis using left middle frontal gyrus fALFF yielded an apparent area under the curve of 0.81 for discriminating SA from CS in this sample.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Patients with CS and SA demonstrate distinct patterns of abnormal spontaneous brain activity. Exploratory associations, particularly in the frontal lobe, were observed with visual acuity loss in amblyopia and may be associated with differing neuropathological states between the 2 conditions. These findings provide neuroimaging evidence that contributes to the understanding of strabismus and amblyopia pathophysiology and may inform future research into neural markers of disease progression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosures&lt;/h3&gt;&lt;div&gt;Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.&lt;/div&gt;&lt;","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 8","pages":"Article 101290"},"PeriodicalIF":5.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographic Atrophy Size Progression Correlates Better with Longitudinal Changes in Quantitative Contrast Sensitivity than Visual Acuity","authors":"Filippos Vingopoulos MD,&nbsp;Marta Stevanovic MD,&nbsp;Peyman Razavi MD,&nbsp;Francesco Romano MD,&nbsp;Xinyi Ding MD,&nbsp;Jocelyn Rodriquez MD,&nbsp;Grace Baldwin MD,&nbsp;Hanna Choi,&nbsp;Raviv Katz MSc,&nbsp;Deeba Husain MD,&nbsp;Leo A. Kim MD, PhD,&nbsp;Joan W. Miller MD,&nbsp;Demetrios G. Vavvas MD, PhD,&nbsp;John B. Miller MD","doi":"10.1016/j.xops.2026.101206","DOIUrl":"10.1016/j.xops.2026.101206","url":null,"abstract":"<div><h3>Purpose</h3><div>Investigate the cross-sectional and longitudinal correlations between total geographic atrophy (GA) size and quantitative contrast sensitivity function (qCSF).</div></div><div><h3>Design</h3><div>Prospective, cross-sectional, and longitudinal observational study between November 2018 and March 2023 at Massachusetts Eye and Ear.</div></div><div><h3>Subjects</h3><div>A total of 83 foveal involving GA eyes cross-sectionally and 30 foveal involving GA eyes longitudinally.</div></div><div><h3>Methods</h3><div>Contrast sensitivity (CS) was measured with the qCSF device along with same day spectral-domain OCT and fundus autofluorescence (FAF). Geographic atrophy was defined as hypoautofluorescent lesions on FAF corresponding to complete retinal pigment epithelium and outer retinal atrophy on spectral-domain OCT. Total GA size was measured on FAF using the semiautomatic Heidelberg Region Finder tool. Mixed-effects multivariate regression models were performed to evaluate correlations between GA size, qCSF metrics, and visual acuity (VA).</div></div><div><h3>Main Outcome Measures</h3><div>Total GA size, longitudinal changes in total GA size, qCSF outcomes (area under the logarithm of contrast sensitivity function [AULCSF], low contrast VA [LCVA], CS thresholds at 1–18 cycles per degree [cpd]), and longitudinal changes in qCSF outcomes.</div></div><div><h3>Results</h3><div>Cross-sectionally (n = 83), total GA was associated with multiple qCSF outcomes including AULCSF and CS thresholds at 1, 1.5, 3, 6, and 12 cpd (β = –0.23 to –0.39, all <em>P</em> &lt; 0.05), but was not associated with VA (β = 0.08, <em>P</em> = 0.47). At 17.2 months follow-up (range: 6–37) (n = 30), an average increase of 1 mm² in total GA size was associated with a nonstatistically significant decrease of 0.01 in VA (<em>P</em> = 0.88), but a statistically significant decrease in CS (–0.05 for AUCLSF, –0.05 for LCVA, –0.04 for 1 cpd, –0.05 for 1.5 cpd, and –0.06 for 3 cpd, all <em>P</em> &lt; 0.05). Standardized regression coefficients suggest that the statistically significant decrease in CS metrics per mm² of GA size increase are 11-fold to 20-fold bigger compared to the nonstatistically significant decrease in VA (–0.33 to –0.62 for qCSF versus –0.03 for VA).</div></div><div><h3>Conclusions</h3><div>Total GA and longitudinal change in GA size were found to be associated with significant changes in qCSF CS, but not with VA or change in VA. Contrast sensitivity seems to be a better functional endpoint to measure treatment effects in GA.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 8","pages":"Article 101206"},"PeriodicalIF":5.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Driven Multimodal Prediction of 10-Year Incident Glaucoma Integrating Genetic and Deep Learning–Derived Imaging Features","authors":"Fengze Wu,&nbsp;Xiaoyi Raymond Gao PhD","doi":"10.1016/j.xops.2026.101292","DOIUrl":"10.1016/j.xops.2026.101292","url":null,"abstract":"<div><h3>Purpose</h3><div>Glaucoma is the leading cause of irreversible blindness worldwide. It often remains asymptomatic until advanced stages. Hence, accurate prediction of glaucoma is crucial for timely intervention to prevent vision loss.</div></div><div><h3>Design</h3><div>Population-based prospective cohort study.</div></div><div><h3>Subjects</h3><div>The UK Biobank participants had available color fundus photographs (CFPs), genetic data, and ocular measurements and were free of glaucoma at baseline. The primary analytic cohort for strictly defined incident primary open-angle glaucoma (POAG) comprised 340 cases and 9374 controls; the secondary broadly defined POAG cohort comprised 1241 cases and 34 216 controls.</div></div><div><h3>Methods</h3><div>We developed an interpretable, multimodal machine learning (ML) framework to predict 10-year incident POAG. The framework integrated 5 feature domains: deep learning (DL)–derived CFP features, ocular measurements, polygenic risk scores (PRS), physical and lifestyle factors, and electronic health records. Deep learning–derived imaging features included a CFP glaucoma score and automated vertical cup-to-disc ratio estimation. We benchmarked ten ML algorithms to identify the optimal model. We applied SHapley Additive exPlanations (SHAP) for model interpretability and feature contribution.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome was incident POAG defined by International Classification of Diseases 10 code H40.1. A secondary broad POAG phenotype incorporated H40.1, H40.0, and H40.9, while excluding other glaucoma subtypes.</div></div><div><h3>Results</h3><div>In the strictly defined POAG analysis, XGBoost achieved the strongest overall performance for 10-year incident glaucoma prediction, with an area under the receiver operating characteristic curve of 0.927 (95% confidence interval, 0.895–0.959), high sensitivity (0.685) at a fixed specificity of 0.95, and excellent calibration (Brier score, 0.024). The corresponding XGBoost model for broadly defined POAG showed modestly lower discrimination while maintaining similarly strong calibration. Incremental modeling demonstrated that both PRS and DL-derived imaging features provided complementary predictive value beyond traditional clinical factors. SHapley Additive exPlanations analysis identified the CFP DL score, age, PRS, and intraocular pressure as the most influential predictors. A reduced model using only the top 4 SHAP-ranked features retained performance comparable to the all-features multimodal model.</div></div><div><h3>Conclusions</h3><div>Our multimodal ML framework integrating genetic and DL-derived imaging features enables accurate and interpretable prediction of incident POAG.</div></div><div><h3>Financial Disclosures</h3><div>The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 8","pages":"Article 101292"},"PeriodicalIF":5.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Pupil Light Reflex Metrics in Glaucoma: Insights from a Systematic Review and Meta-Analysis","authors":"Mohammadreza Moniritilaki MSc,&nbsp;Peter Wagner PhD,&nbsp;Sieu K. Khuu PhD","doi":"10.1016/j.xops.2026.101225","DOIUrl":"10.1016/j.xops.2026.101225","url":null,"abstract":"<div><h3>Topic</h3><div>This systematic review and meta-analysis aimed to identify the most affected pupil light reflex (PLR) metrics and determine the optimal stimulus conditions for detecting glaucomatous deficits.</div></div><div><h3>Clinical Relevance</h3><div>The PLR is altered in glaucoma and understanding the basis of this change may provide a useful method for disease detection and progression monitoring.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across PubMed, Embase, and Google Scholar databases from June 2023 to April 2025. Studies evaluating PLR in glaucoma patients and healthy controls were included. Data extraction focused on PLR metrics such as amplitude of constriction, velocity of constriction and dilation, latency of constriction and dilation, and postillumination pupil response (PIPR). A meta-analysis was performed (Hedges' g) to determine the impact of glaucoma on each PLR metric. Subgroup and moderator analyses were conducted to assess the influence of dark adaptation, stimulus duration, and stimulus color on PLR metrics and to examine the relationship between PLR metrics and age, retinal nerve fiber layer (RNFL) thickness, and mean deviation (MD). This systematic review is registered with PROSPERO (CRD420251079002).</div></div><div><h3>Results</h3><div>A meta-analysis revealed that the amplitude of constriction (the most affected metric), latency of constriction, velocity of constriction, and PIPR were significantly affected in mild glaucoma. Subgroup analysis suggested that the testing conditions involving a stimulus lasting &gt;1 second, after dark adaptation of &lt;5 minutes, are most sensitive for detecting PLR deficits. Moderator analysis indicated that age, RNFL thickness, and MD were associated with variations in PLR metrics. In severe glaucoma, the amplitude of constriction, duration of dilation, velocity of constriction, and PIPR showed the largest effect sizes (ESs). Overall, severe glaucoma led to larger ESs, indicating greater change in PLR metrics was associated with disease severity.</div></div><div><h3>Conclusions</h3><div>These findings suggest that the amplitude of constriction is the most affected PLR metric in both mild and severe glaucoma. Furthermore, our results indicate that a stimulus lasting &gt;1 second, when presented after a dark adaptation of &lt;5 minutes, may represent the most sensitive condition for detecting amplitude of constriction deficits in mild glaucoma.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 7","pages":"Article 101225"},"PeriodicalIF":5.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148310707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epiretinal Membrane Is Associated with Acquired Vitelliform Lesion Morphometrics in Intermediate Age-Related Macular Degeneration","authors":"Alberto Quarta MD,&nbsp;Rouzbeh Abbasgholizadeh MD,&nbsp;Jianfeng Huang MD,&nbsp;Shinichiro Chujo MD, PhD,&nbsp;Ceren Soylu MD,&nbsp;Sweetha Bindu Velaga Optom,&nbsp;Alireza Mahmoudi MD,&nbsp;Sophiana Lindeberg,&nbsp;Mai Alhelaly MD,&nbsp;Muneeswar G. Nittala PhM,&nbsp;Giulia Corradetti MD,&nbsp;Rodolfo Mastropasqua MD, PhD,&nbsp;Charles Wykoff MD,&nbsp;Srinivas R. Sadda MD","doi":"10.1016/j.xops.2026.101228","DOIUrl":"10.1016/j.xops.2026.101228","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the impact of epiretinal membrane (ERM) on the structural characteristics of acquired vitelliform lesions (AVLs) in eyes with intermediate age-related macular degeneration (iAMD).</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Participants</h3><div>Eyes of patients with iAMD-associated AVLs were identified from a tertiary referral center database.</div></div><div><h3>Methods</h3><div>Multimodal imaging, including spectral-domain OCT, was reviewed. Eyes were stratified according to the presence (ERM + AVL) or absence (AVL-only) of ERM. Quantitative OCT parameters, including apical AVL height and width, and qualitative structural features such as intraretinal hyperreflective foci (IHRF), ellipsoid zone (EZ), and external limiting membrane (ELM) disruption, and AVL location relative to drusen, were assessed by masked graders. Effect sizes were calculated using Hedges' <em>g</em>. Group comparisons were performed using appropriate parametric or nonparametric tests.</div></div><div><h3>Main Outcome Measures</h3><div>Differences in AVL structural characteristics between eyes with and without ERM.</div></div><div><h3>Results</h3><div>A total of 234 eyes with age-related macular degeneration (AMD)-associated AVLs were included, of which 17 eyes had concomitant ERM. Eyes with ERM demonstrated significantly greater apical AVL height compared with AVL-only eyes (169.9 ± 52.5 μm vs. 134.8 ± 55.0 μm; <em>P</em> = 0.016). Acquired vitelliform lesion width was greater in the ERM + AVL group, although this difference did not reach statistical significance (811.1 ± 251.0 μm vs. 676.8 ± 416.0 μm; <em>P</em> = 0.057). The prevalence of IHRF, EZ disruption, ELM disruption, and AVL location over drusen did not differ significantly between groups. Effect size analysis demonstrated a moderate positive effect for apical AVL height (Hedges' <em>g</em> ≈ 0.65; 95% confidence interval [CI] ∼0.15 to 1.10), whereas AVL width showed a small-to-moderate effect size with CIs crossing 0.</div></div><div><h3>Conclusions</h3><div>In eyes with AMD-associated AVLs, the presence of ERM is associated with increased AVL height without corresponding differences in other outer retinal structural features. These findings suggest that vitreomacular traction may selectively influence AVL configuration. Longitudinal studies are needed to determine whether traction-related modulation of AVL morphology impacts AMD disease progression and AVL collapse.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 7","pages":"Article 101228"},"PeriodicalIF":5.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13315181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148363988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tropomyosin-Related Kinase Receptor Type B Agonism in Geographic Atrophy—The Translational Challenges from Preclinical Data to a First-in-Human Trial","authors":"David Brown MD,&nbsp;Oliver Zeitz MD,&nbsp;Clare Bailey MD,&nbsp;Sunir Garg MD,&nbsp;Karl Csaky MD,&nbsp;James Talks MD,&nbsp;Sobha Sivaprasad MD,&nbsp;Peter M. Benz PhD,&nbsp;Rolf Herrmann PhD,&nbsp;Remko A. Bakker PhD,&nbsp;Sebastian Bandholtz PhD,&nbsp;Ankit Mittal PhD,&nbsp;Qihong Huang PhD,&nbsp;Serge Kosobokovs MD,&nbsp;Gudrun Simons PhD,&nbsp;Andrea Giani MD,&nbsp;Jochen Huber PhD,&nbsp;Martin Gliem MD","doi":"10.1016/j.xops.2026.101216","DOIUrl":"10.1016/j.xops.2026.101216","url":null,"abstract":"<div><h3>Objective</h3><div>To report results of the first-in-human trial of intravitreal tropomyosin-related kinase receptor type B (TrkB) agonist BI 754132 in participants with geographic atrophy (GA). To discuss BI 754132 clinical data in the context of the preclinical findings and their translation into human data.</div></div><div><h3>Design</h3><div>An open-label, uncontrolled, nonrandomized phase I trial (NCT04002310) assessing the safety, tolerability, and pharmacokinetics of BI 754132 in participants with GA supported by preclinical data.</div></div><div><h3>Participants</h3><div>Participants with GA recruited between July 2019 and August 2022 in the United States and UK.</div></div><div><h3>Methods</h3><div>Clinical trial comprising a single rising dose (SRD) part (n = 15) and multiple dose (MD) part (n = 3). Of 18 participants treated, 16 received a single dose of BI 754132 0.3 to 6 mg (SRD, n = 15; MD, n = 1) and 2 received 3 doses each of BI 754132 6 mg (MD part).</div></div><div><h3>Main Outcome Measures</h3><div>The primary SRD endpoint was the incidence of ocular and systemic dose-limiting events until day 100; the primary MD endpoint was treatment-related adverse events (AEs) until day 155. Exploratory endpoints included change from baseline in best-corrected visual acuity (BCVA), GA lesion area, central retinal thickness, and selected electroretinogram parameters.</div></div><div><h3>Results</h3><div>Preclinical data supported a potential treatment effect and a favorable safety profile of BI 754132, supporting clinical development. In the phase I study (SRD and MD parts), 12 of 18 (67%) participants had an AE; of which, 4 had ischemic optic neuropathy in the study eye. Considering the frequency of ischemic optic neuropathy in the absence of efficacy data, the benefit–risk assessment of BI 754132 could not be considered as positive, and the clinical study was terminated. There was a mild increase in central retinal thickness (≤25 μm) of all study eyes. No relevant changes in BCVA, GA lesion area, or electroretinogram parameters were noted.</div></div><div><h3>Conclusions</h3><div>Clinical data suggested a potential association between BI 754132 and development of ischemic optic neuropathy. Although the underlying mechanisms remain unclear, these data warrant caution during further exploration of TrkB agonism in GA and highlight the role of monitoring safety data during early clinical development, especially when studying new modes of action.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 7","pages":"Article 101216"},"PeriodicalIF":5.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease and Participant-Related Correlates of Genetic Testing Completion for Hereditary Eye Disorders in a Cohort of over 1400 Patients","authors":"Dorothy T. Wang,&nbsp;Bani Antonio-Aguirre MD, MPH,&nbsp;Maria Ludovica Ruggeri MD,&nbsp;Christy H. Smith ScM, CGC,&nbsp;Kelsey S. Guthrie MGC, CGC,&nbsp;Carolyn D. Applegate MGC, CGC,&nbsp;Annabelle Pan MD,&nbsp;Setu P. Mehta,&nbsp;Kurt A. Dreger,&nbsp;Ishrat Ahmed MD, PhD,&nbsp;Jefferson J. Doyle MBBChir, PhD,&nbsp;Mandeep S. Singh MD, PhD","doi":"10.1016/j.xops.2026.101218","DOIUrl":"10.1016/j.xops.2026.101218","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To identify clinical and demographic predictors of genetic testing completion and diagnostic yield among patients with genetic eye disorders (GEDs) at a large US tertiary academic center.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;A retrospective cohort study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;Patients with clinically diagnosed GEDs evaluated at the Wilmer Eye Institute’s Genetic Eye Disease Center between 2002 and 2025.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Demographic, clinical, and genetic testing data were extracted. Bivariate analyses and multivariable logistic regression identified factors associated with genetic testing completion and molecular diagnosis. Subgroup analyses examined racial disparities between Black, non-Hispanic White, and Other race participants.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Proportion of patients completing genetic testing, molecular diagnostic yield, and clinical/demographic predictors of each.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Of 1466 participants (median age at presentation 44 years, symptom onset 28 years; median follow-up 6 years), 74% (1088) completed genetic testing, with a likely molecular diagnosis achieved in 62%, inconclusive results in 22%, and no diagnosis in 16%. Genetic testing completion was more likely among younger participants with earlier symptom onset and longer follow-up. Likely molecular diagnosis was more likely in participants with earlier symptom onset, worse visual acuity, male sex, and syndromic or X-linked phenotypes. Black and Other race participants had significantly lower odds of completing genetic testing (Black: odds ratio [95% confidence interval] 0.40 [0.30–0.53]; Other: 0.57 [0.36–0.92]) and receiving a likely molecular diagnosis (Black: 0.37 [0.26–0.51]; Other: 0.58 [0.35–0.98]), and consistently exhibited worse visual acuity at both baseline and follow-up. Notably, among Black and Other race participants, disparities in genetic testing completion and visual outcomes persisted despite equivalent or shorter time from presentation to genetic testing completion, suggesting barriers arise independently of delays in care engagement. We identified 118 causative genes among participants with likely molecular diagnoses, with &lt;em&gt;ABCA4&lt;/em&gt;, &lt;em&gt;USH2A&lt;/em&gt;, &lt;em&gt;PRPH2&lt;/em&gt;, &lt;em&gt;RHO&lt;/em&gt;, and &lt;em&gt;BEST1&lt;/em&gt; accounting for 47% of cases.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This is the largest single-center GED genetic testing cohort reported in the United States and reveals significant disparities in genetic testing completion and yield by race, age, sex, and disease-level factors. Our findings underscore the need to expand early access to genetic testing, diversify genomic databases, and address systemic barriers to ensure equity in GED diagnosis, clinical trial access, and delivery of emerging therapies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosures&lt;/h3&gt;&lt;div&gt;Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 7","pages":"Article 101218"},"PeriodicalIF":5.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nationwide Multicenter Survey of Severe Complications of Strabismus Surgery in Japan: Japanese Strabismus Surgery Study","authors":"Akinari Yamamoto MD,&nbsp;Manabu Miyata MD, PhD,&nbsp;Shinya Nakao MD,&nbsp;Takashi Negishi MD, PhD,&nbsp;Toshiaki Goseki MD, PhD,&nbsp;Sachiko Nishina MD, PhD,&nbsp;Akiko Hikoya MD, PhD,&nbsp;Miho Sato MD, PhD,&nbsp;Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.xops.2026.101243","DOIUrl":"10.1016/j.xops.2026.101243","url":null,"abstract":"<div><h3>Objective</h3><div>The increasing incidence of esotropia, potentially associated with excessive smartphone use, highlights the importance of ensuring the safety of strabismus surgery. This nationwide questionnaire survey, conducted as the Japanese Strabismus Surgery (JASS) study, aimed to estimate the incidence of severe complications associated with strabismus surgery and to characterize perioperative management practices in Japan.</div></div><div><h3>Design</h3><div>Nationwide, multicenter, questionnaire-based survey study.</div></div><div><h3>Participants</h3><div>All strabismus specialists affiliated with the Japanese Association for Strabismus and Amblyopia.</div></div><div><h3>Methods</h3><div>We conducted the survey between July and August 2025. We developed a structured questionnaire using Research Electronic Data Capture.</div></div><div><h3>Main Outcome Measures</h3><div>Number of severe complications, including infectious endophthalmitis, orbital cellulitis, anterior segment ischemia (grade 3 or higher), and scleral perforation with retinal detachment, as well as perioperative management protocols.</div></div><div><h3>Results</h3><div>Of 210 specialists, 99 completed the questionnaire (response rate, 47.1%). After excluding 2 nonsurgical respondents, we analyzed data from 97 active surgeons (mean experience, 28.7 ± 12.2 years) covering 108 623 strabismus surgeries. Incidence rates (per 100 000 surgeries) of severe complications were 0.92 (95% confidence interval [CI], 0.02–5.13) for infectious endophthalmitis, 1.84 (95% CI, 0.22–6.65) for orbital cellulitis, 8.29 (95% CI, 3.79–15.73) for anterior segment ischemia, and 3.68 (95% CI, 1.00–9.43) for scleral perforation with retinal detachment. For perioperative management, nearly all surgeons (91.8%) used povidone-iodine immediately before surgery, all (100%) prescribed postoperative antibiotics, and most (74.2%) used adhesive drapes. A large majority (87.6%) conducted the first postoperative follow-up examination on day 1.</div></div><div><h3>Conclusions</h3><div>This JASS study demonstrates that severe complications associated with strabismus surgery are exceedingly rare in Japan. Stringent, standardized management protocols, particularly for infection control and early postoperative follow-up, may contribute to this high level of safety.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 7","pages":"Article 101243"},"PeriodicalIF":5.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}