Ophthalmology science最新文献

{"title":"Long-read Sequencing in Inherited Retinal Dystrophies: A Systematic Review","authors":"Mariam Ibrahim MSc , Alain Chebly PhD , Said El Shamieh PhD","doi":"10.1016/j.xops.2026.101069","DOIUrl":"10.1016/j.xops.2026.101069","url":null,"abstract":"<div><h3>Topic</h3><div>Inherited retinal dystrophies (IRDs) encompass a group of phenotypically and genetically heterogeneous disorders leading to progressive visual impairment. The advent of next-generation sequencing (NGS) has substantially improved genetic diagnosis rates; however, approximately 30% of IRD cases remain genetically unsolved (“missing heritability”). Long-read sequencing (LRS) has emerged as a complementary approach for identifying complex, inaccessible variants, including structural and deep intronic variants. This study systematically reviews the application of LRS in IRD genetics with descriptive synthesis.</div></div><div><h3>Clinical Relevance</h3><div>Inherited retinal dystrophies collectively affect approximately 1 in 3000 individuals and are a leading cause of inherited blindness worldwide. Accurate molecular diagnosis informs prognosis, genetic counseling, and eligibility for emerging gene therapies. While NGS represents the current standard diagnosis, its inability to capture certain variant types limits its diagnostic sensitivity. Integrating LRS could bridge this diagnostic gap and enhance personalized management.</div></div><div><h3>Methods</h3><div>A systematic search on PubMed (September 1, 2025) identified 26 studies investigating the use of LRS in patients with IRD (published between 2018 and September 1, 2025). Studies were eligible if they applied LRS for the genetic diagnosis of IRDs in humans, were available in full-text English, and reported IRD variants. Data extraction and synthesis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological quality was assessed using Murad’s tool for case reports and case series, the Joanna Briggs Institute Checklist for Case Series, and the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The review was registered prospectively on the International Prospective Register of Systematic Reviews (identifier, CRD42024602173).</div></div><div><h3>Results</h3><div>Our analysis identified 88 IRD variants described by LRS. Of these, 31% were structural, 31% single nucleotide, 19% splice site, 11% insertions/deletions, and 8% deep intronic. Long-read sequencing expanded the IRD genetic landscape by identifying or refining pathogenic variants in 34 genes across 81 patients. Studies also validated LRS for phasing and resolving technically challenging regions.</div></div><div><h3>Conclusions</h3><div>Long-read sequencing overcomes key limitations of short-read sequencing in the genetic diagnosis of IRDs. Although existing studies show high analytical rigor and increased diagnostic yield, most lack formal diagnostic accuracy metrics. Current evidence supports the potential incorporation of LRS into clinical workflows, with further prospective studies needed to define diagnostic accuracy, clinical utility, and implementation standards.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors have no proprietary or commercial ","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101069"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: Henriques et al Correspondence Re: Most et al: Can Multimodal Large Language Models Diagnose Diabetic Retinopathy from Fundus Photos? A Quantitative Evaluation","authors":"Jesse A. Most BA , Dirk-Uwe G. Bartsch PhD , Shyamanga Borooah FRCOphth, PhD","doi":"10.1016/j.xops.2026.101064","DOIUrl":"10.1016/j.xops.2026.101064","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101064"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BEnchmarking Large Language Models for Ophthalmology (BELO): An Expert-Curated Data Set and Evaluation Framework for Knowledge and Reasoning","authors":"Sahana Srinivasan BEng , Xuguang Ai MSc , Thaddaeus Wai Soon Lo BEng , Aidan Gilson MD , Minjie Zou MD, MMed , Ke Zou PhD , Hyunjae Kim PhD , Mingjia Yang BEng , Krithi Pushpanathan MSc , Samantha Min Er Yew MSc , Wan Ting Loke MSc , Jocelyn Hui Lin Goh BEng , Yibing Chen BEng , Yiming Kong , Emily Yuelei Fu MSc , Michelle Ong BEng , Kristen Nwanyanwu MD, MHS , Amisha Dave MD , Kelvin Zhenghao Li MBBS, MMed , Chen-Hsin Sun MD. MMed , Yih-Chung Tham PhD","doi":"10.1016/j.xops.2025.101050","DOIUrl":"10.1016/j.xops.2025.101050","url":null,"abstract":"<div><h3>Purpose</h3><div>Current benchmarks evaluating large language models (LLMs) in ophthalmology are narrow and disproportionately prioritize accuracy. We introduce BEnchmarking LLMs for Ophthalmology (BELO), a standardized evaluation benchmark developed through multiple rounds of expert checking by 13 ophthalmologists. BEnchmarking LLMs for Ophthalmology assesses ophthalmology-related knowledge and reasoning quality.</div></div><div><h3>Subjects</h3><div>This study did not involve human participation.</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Methods</h3><div>Using keyword matching and a fine-tuned PubMed Bidirectional Encoder Representations from Transformers model, we curated ophthalmology-specific multiple-choice questions (MCQs) from diverse medical data sets (Basic and Clinical Science Course [BCSC], Multi-Subject Multi-Choice Dataset for Medical domain [MedMCQA], Medical Question Answering [MedQA], Biomedical Semantic Indexing and Question Answering [BioASQ], and PubMed Question Answering [PubMedQA]). The data set underwent multiple rounds of expert checking. Duplicate and substandard questions were systematically removed. Ten ophthalmologists refined the explanations of each MCQ's correct answer. This was further adjudicated by 3 senior ophthalmologists. To illustrate BELO's utility, we evaluated 8 LLMs (OpenAI o1, o3-mini, GPT-5, GPT-4o, DeepSeek-R1, MedGemma-4B, Llama-3-8B, and Gemini 1.5 Pro).</div></div><div><h3>Main Outcome Measures</h3><div>The 8 LLMs were evaluated in terms using accuracy, macro-F1, and 5 text-generation metrics (Recall-Oriented Understudy for Gisting Evaluation, BERTScore, BARTScore, Metric for Evaluation of Translation with Explicit Ordering, and AlignScore). In a further evaluation involving human experts, 2 ophthalmologists qualitatively reviewed 50 randomly selected outputs for accuracy, comprehensiveness, and completeness.</div></div><div><h3>Results</h3><div>BEnchmarking LLMs for Ophthalmology consists of 900 high-quality, expert-reviewed questions aggregated from 5 sources: BCSC (260), BioASQ (10), MedMCQA (572), MedQA (40), and PubMedQA (18). To demonstrate BELO's utility, we conducted a series of benchmarking exercises. In the quantitative evaluation, GPT-5 achieved the highest accuracy (0.90, 95% confidence interval [CI]: 0.89–0.92) and macro-F1 score (0.91, 95% CI: 0.89–0.93). On the other hand, the models' performance on text-generation metrics varied and were generally suboptimal, with scores ranging from 20.4 to 72.0 (out of 100, excluding the BARTScore metric), indicating room for improvement in clinical reasoning. In expert evaluations, GPT-4o was rated highest for accuracy and readability, while Gemini 1.5 Pro scored highest for completeness. A public leaderboard has been established to promote transparent evaluation and reporting. Importantly, the BELO data set will remain a hold-out, evaluation-only benchmark to ensure fair and reproducible comparisons o","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101050"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable Aging Signatures in Human Retinal Cell Types Revealed by Single-Cell RNA Sequencing and Sparse Logistic Regression","authors":"Luning Yang PhD ,&nbsp;Sen Lin MS ,&nbsp;Yiwen Tao BS ,&nbsp;Qi Pan MS ,&nbsp;Tengda Cai MS ,&nbsp;Yunyan Ye PhD ,&nbsp;Jianhui Liu PhD ,&nbsp;Yang Zhou PhD ,&nbsp;Yongqing Shao MS ,&nbsp;Quanyong Yi PhD ,&nbsp;Zen Huat Lu PhD ,&nbsp;Lie Chen PhD ,&nbsp;Gareth McKay PhD ,&nbsp;Richard Rankin PhD ,&nbsp;Fan Li PhD ,&nbsp;Weihua Meng PhD","doi":"10.1016/j.xops.2025.101062","DOIUrl":"10.1016/j.xops.2025.101062","url":null,"abstract":"<div><h3>Purpose</h3><div>To characterize cell-type-specific transcriptional changes during human retinal aging and develop machine learning (ML) model for cellular age discrimination in a Chinese cohort.</div></div><div><h3>Design</h3><div>Cross-sectional, laboratory-based observational study.</div></div><div><h3>Participants</h3><div>Eighteen unfrozen retinas from 12 Chinese donors (9 young, 34-55 y; 9 old, 68-92 y).</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing (10x, v3.1) generated 223 612 cells, batch-corrected with single-cell variational inference; age-related signatures were defined by intersecting single-cell and pseudobulk differentially expressed genes (DEGs), then cell-type-specific panels were rank-ordered with L1-regularized logistic regression plus recursive feature elimination and interpreted through hallmark-pathway enrichment and transcription factor (TF) regulon mapping.</div></div><div><h3>Main Outcome Measures</h3><div>Age-related cellular composition shifts; cell-type-specific DEGs; ML classifier accuracy and feature rankings; TF regulon activity changes.</div></div><div><h3>Results</h3><div>Eleven major retinal cell populations were identified. Aging showed declining rod-to-cone ratios, reduced bipolar cell (BC) proportions among interneurons, and increased astrocyte abundance. Müller glial cells exhibited the most pronounced transcriptional changes, followed by BCs and rods. Machine learning classifiers achieved 80% to 96% accuracy across cell types (microglia 96%, horizontal cells [HCs] 93%, BCs 91%, cones 90%, rods 89%). Shared aging signatures included mitochondrial dysfunction and inflammatory activation. Cell-specific vulnerabilities emerged: mitochondria-centric stress in rods/BCs, proteostasis-retinoid metabolism in cones, and structural-RNA maintenance in HCs.</div></div><div><h3>Conclusions</h3><div>This study provides the first ML derived, cell-type-specific aging signatures for human retina in a Chinese cohort, revealing both conserved molecular hallmarks and distinctive cellular vulnerabilities that inform targeted therapeutic strategies for retinal aging.</div></div><div><h3>Financial Disclosure(s)</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 3","pages":"Article 101062"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Virtual Reality Simulated Alternate Cover Test to Evaluate Adults with Strabismus","authors":"Yeabsira Mesfin ,&nbsp;Patrick Takla ,&nbsp;Maanasa Indaram MD ,&nbsp;Julius T. Oatts MD","doi":"10.1016/j.xops.2026.101077","DOIUrl":"10.1016/j.xops.2026.101077","url":null,"abstract":"<div><h3>Objective</h3><div>Obtaining precise strabismus measurements is key in the diagnosis and management of strabismus in adults. Virtual reality (VR) has the potential to address the limitations of the standard alternate cover test (ACT) in measuring strabismus. The goal of this study was to evaluate the performance of a VR-simulated ACT in adults with strabismus.</div></div><div><h3>Design</h3><div>Prospective cohort study.</div></div><div><h3>Participants</h3><div>Eligible consecutive participants ≥18 years with manifest strabismus ≥5 prism diopters (PD) at either distance or near were prospectively enrolled.</div></div><div><h3>Intervention</h3><div>Each patient underwent a VR-simulated ACT with eye-tracking technology (Olleyes VisuALL) followed by an ACT by a masked pediatric ophthalmologist. Bland–Altman plots, intraclass correlation coefficient (ICC), and Spearman correlation were used to compare the limits of agreement (LOA) and association between the 2 examinations for the entire cohort as well as those with deviations ≥10 PD.</div></div><div><h3>Main Outcome Measures</h3><div>Level of agreement between VR and standard strabismus measurements obtained from the VR and ACT.</div></div><div><h3>Results</h3><div>Of the 61 participants enrolled, 56 completed the VR test at near and 50 at distance. At distance, VR measurements were 0.88 PD higher than the ACT (upper LOA: 19.3, lower LOA: –17.6). At near, VR measurements were 0.28 PD higher than the ACT (upper LOA: 26.1, lower LOA: –25.5). For patients with manifest strabismus ≥10 PD, VR measurements were 0.26 PD lower than the ACT at distance (upper LOA: 19.5, lower LOA: –20.1) and at 3.97 PD lower at near (upper LOA: 18.8, lower LOA: –2). Wider variability was observed in patients with larger deviations. Significant correlations between VR and ACT measurements were observed at distance greater than near (ICC = 0.78, <em>P</em> &lt; 0.0001; ICC = 0.57, <em>P</em> &lt; 0.001, respectively). Patients with deviations ≥10 PD exhibited similar agreement (ICC: 0.72, <em>P</em> &lt; 0.0001; near: ICC = 0.64, <em>P</em> &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>A VR-simulated ACT demonstrated good correlation to standard strabismus measurements at distance and moderate correlation at near. The VR device underestimated deviations with larger deviations and tended to overestimate in those with smaller deviations. Virtual reality with eye-tracking technology holds promise in the assessment of adults with strabismus.</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 3","pages":"Article 101077"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of High-Density Lipoprotein Cholesterol with Macular Structure in Nonglaucomatous Individuals","authors":"Taiga Inooka MD, PhD ,&nbsp;Ryo Tomita MD, PhD ,&nbsp;Ayana Suzumura MD, PhD ,&nbsp;Shota Fujikawa MD ,&nbsp;Yuki Kimura MD ,&nbsp;Taro Kominami MD, PhD ,&nbsp;Tetsuhito Kojima MD, PhD ,&nbsp;Shinji Ueno MD, PhD ,&nbsp;Yasuki Ito MD, PhD ,&nbsp;Koji M. Nishiguchi MD, PhD ,&nbsp;Kenya Yuki MD, PhD","doi":"10.1016/j.xops.2026.101073","DOIUrl":"10.1016/j.xops.2026.101073","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association between serum high-density lipoprotein cholesterol (HDL-C) levels and ganglion cell complex (GCC) thickness in a nonglaucomatous Japanese population.</div></div><div><h3>Design</h3><div>A retrospective cross-sectional observational study.</div></div><div><h3>Participants</h3><div>We included 588 nonglaucomatous Japanese adults who underwent comprehensive ophthalmic and systemic health screening.</div></div><div><h3>Methods</h3><div>Participants underwent OCT imaging, anthropometric measurements, including brachial–ankle pulse wave velocity, spirometry, and hematologic profiling. Multivariable linear regression models were used to assess the association between HDL-C levels and GCC thickness. Covariates were selected using a stepwise variable selection procedure, with the final model including age and axial length. A piecewise linear regression model further evaluated the association across different HDL-C ranges.</div></div><div><h3>Main Outcome Measures</h3><div>Average GCC thickness.</div></div><div><h3>Results</h3><div>Older age (<em>P</em> = 0.002), longer axial length (<em>P</em> &lt; 0.001), and higher HDL-C levels (<em>P</em> &lt; 0.001) were significantly associated with thinner GCC thickness. A nonlinear relationship was observed, with GCC thickness inversely associated with HDL-C levels outside the 60 to 67 mg/dL range (<em>P</em> = 0.005).</div></div><div><h3>Conclusions</h3><div>High-density lipoprotein cholesterol levels are significantly associated with GCC thickness in nonglaucomatous individuals, which suggests a potential role of lipid metabolism in early neuroretinal thinning. High-density lipoprotein cholesterol may serve as a biomarker for neurodegenerative changes, even before glaucomatous alterations become clinically apparent.</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 3","pages":"Article 101073"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Feature Segmentation of Ultra-Widefield OCT Images","authors":"John D. Jackson MD ,&nbsp;Mani K. Woodward MCR ,&nbsp;David A. Sutter ,&nbsp;Aaron S. Coyner PhD ,&nbsp;Carol X. Wang ,&nbsp;Susan R. Ostmo MS ,&nbsp;Michael F. Chiang MD, MA ,&nbsp;Yali Jia PhD ,&nbsp;David Huang MD, PhD ,&nbsp;Yifan Jian PhD ,&nbsp;J. Peter Campbell MD, MPH ,&nbsp;Benjamin K. Young MD, MS","doi":"10.1016/j.xops.2025.101029","DOIUrl":"10.1016/j.xops.2025.101029","url":null,"abstract":"<div><h3>Objective or Purpose</h3><div>To develop a lightweight neural network for automated cross-sectional and en face segmentation of ultra-widefield (UWF) OCT images acquired for retinopathy of prematurity screening.</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Subjects</h3><div>Twenty-five infants with a birth weight &lt;1500 g or gestational age &lt;31 weeks were scanned using a portable, handheld, swept-source UWF-OCT device.</div></div><div><h3>Methods, Intervention, or Testing</h3><div>For cross-sectional B-scans, 3040 B-scans from 5 OCT volumetric scans obtained from 5 patients were segmented by 2 graders for the choroid and retina using custom-built tools in the Napari image viewer. Using these segmentations, a u-net with an EfficientNet-B0 backbone was trained in combination with task-specific augmentations to perform automated segmentation of the retina and choroid data with varying levels of image processing applied. For en face scans, 40 en face images from 20 unique patients were manually segmented by a single grader for retinal vessels. Using these segmentations, a u-net with an EfficientNet-B0 backbone was trained. Validation for both B-scans and en face images was performed using fivefold cross-validation. The fivefold cross-validation metrics were then compared with the metrics obtained by comparing grader segmentations.</div></div><div><h3>Main Outcome Measures</h3><div>The Dice similarity coefficient (DSC) was used to assess B-scan and en face segmentations.</div></div><div><h3>Results</h3><div>The retinal and choroidal b-scan segmentations produced a DSC ± standard deviation of 0.925 ± 0.021 and 0.797 ± 0.062, respectively, averaged across the fivefolds. The en face vasculature segmentation produced a DSC ± standard deviation of 0.625 ± 0.0450.</div></div><div><h3>Conclusions</h3><div>Using u-net convolutional neural networks trained with task-specific augmentations, we developed en face and cross-sectional segmentations for UWF-OCT images, which will facilitate automated quantitative analysis with this novel modality.</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 3","pages":"Article 101029"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual Field Estimation in X-Linked Retinitis Pigmentosa Associated with Retinitis Pigmentosa GTPase Regulator (RPGR) from Image Analysis Using Artificial Intelligence","authors":"Malena Daich Varela MD, PhD ,&nbsp;William Woof PhD ,&nbsp;Yathusha Kumarasamy ,&nbsp;Matthias Monhart BS ,&nbsp;Lynn Kandakji PhD ,&nbsp;Gunjan Naik PhD ,&nbsp;Pallavi Bagga PhD ,&nbsp;Alan Wilter Sousa PhD ,&nbsp;Dun Jack Fu PhD ,&nbsp;Catey Bunce MSc ,&nbsp;Konstantinos Balaskas MD ,&nbsp;Nikolas Pontikos PhD ,&nbsp;Michel Michaelides MD","doi":"10.1016/j.xops.2025.101033","DOIUrl":"10.1016/j.xops.2025.101033","url":null,"abstract":"<div><h3>Purpose</h3><div>To develop an efficient approach to estimating visual field (VF) in patients with X-linked retinitis pigmentosa (RP) based on macular OCT scans.</div></div><div><h3>Design</h3><div>Retrospective analysis of patients who were enrolled in a natural history study at Moorfields Eye Hospital (London, United Kingdom).</div></div><div><h3>Subjects</h3><div>Male patients with genetically confirmed retinitis pigmentosa GTPase regulator (<em>RPGR</em>)-associated RP.</div></div><div><h3>Methods</h3><div>Visual field raw data were exported and analyzed including Visual Field Modeling and Analysis software. Retinal imaging consisted of OCT macular scans. Paired imaging and VF data acquired within a 1-month range were jointly analyzed. Artificial intelligence (AI) was used to automatically segment and quantify macular ellipsoid zone width (EZW), and ellipsoid zone area (EZA).</div></div><div><h3>Main Outcome Measures</h3><div>Functional parameters from static VF testing such as mean sensitivity (MS) and Hill of Vision analysis that included total volume (V_TOT), volume of central 20° (V₂₀), and volume of central 30° (V₃₀) were predicted from EZW and EZA.</div></div><div><h3>Results</h3><div>Patient age ranged from 5 to 55 years old at baseline. A total of 332 OCT-VF pairs were analyzed. Ellipsoid zone area had the highest conditional R² (R²c) and most significant associations with MS and V₂₀. There were significant associations between MS and EZW (<em>P</em> = 0.00176), and MS with EZA (<em>P</em> = 0.0009).</div></div><div><h3>Conclusions</h3><div>This study showed that AI enables efficient acquiring of large amounts of structural OCT parameters, facilitating research and structure-function predictions. The cohort included patients with a wide range of disease severity and statistical significance was achieved with parameters representing a wide range of VF, proving that this method can be applied for patients with milder disease.</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 3","pages":"Article 101033"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: Hiraoka et al: Quantitative Mapping of Posterior Eye Curvature in Children Using Distortion-Corrected OCT: Insights into Temporal Region Morphology","authors":"Nianjia Wang ,&nbsp;Xindi Liu ,&nbsp;Liang Yao","doi":"10.1016/j.xops.2025.101040","DOIUrl":"10.1016/j.xops.2025.101040","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101040"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145969431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining Genetic Cause of Posterior Staphylomas in Eyes with Pathologic Myopia by Whole Exome Sequencing","authors":"Ziye Wang MD ,&nbsp;Changyu Chen MD, PhD ,&nbsp;Yijin Wu MD ,&nbsp;Yuki Nagata PhD ,&nbsp;Toshihiro Tanaka MD, PhD ,&nbsp;Shiqi Xie MD, PhD ,&nbsp;Hongshuang Lu MD, PhD ,&nbsp;Yining Wang MD ,&nbsp;Jianping Xiong MD, PhD ,&nbsp;Liwen Zhang MD ,&nbsp;Koju Kamoi MD, PhD ,&nbsp;Kyoko Ohno-Matsui MD, PhD","doi":"10.1016/j.xops.2025.101058","DOIUrl":"10.1016/j.xops.2025.101058","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To identify genetic variants in posterior staphylomas in eyes with pathologic myopia using whole exome sequencing and to determine possible molecular mechanisms contributing to the pathogenesis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;An observational, case-control study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;Two hundred sixty-four unrelated Japanese patients with myopia (≤ –0.50 diopters) and posterior staphyloma, which was diagnosed by ultra-widefield OCT, 3-dimensional magnetic resonance imaging, and Optos imaging.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Whole exome sequencing was performed on genomic DNA from peripheral blood. After variant filtering, the allelic frequencies were compared with control data obtained from East Asian subsets of the 1000 Genomes Project Phase III, the Exome Aggregation Consortium, and the Japanese Multi-Omics Reference Panel using Fisher exact test. A gene panel was constructed based on 13 staphyloma-associated disorders. Variants showing significant frequency differences (&lt;em&gt;P&lt;/em&gt; ≤ 0.05) and an overlap of the gene panel were analyzed using gene set enrichment analysis with the DAVID Knowledgebase (v2023q4). Protein–protein interaction analysis was performed to assess functional associations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;The statistically associated variants and genes, gene set enrichment analysis results, protein–protein interaction networks, and involvement of basement membrane structures, including the inner limiting membrane (ILM) and Bruch membrane, were studied.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Whole exome sequencing identified 16 656 missense variants in 8628 genes. Comparative allele frequency analyses with public databases revealed 3925 variants that had significantly higher allelic frequencies in the subjects. Of these, 81 genes overlapped with a curated staphyloma-related gene panel and were subjected to gene set enrichment analysis. The findings showed enrichment in basement membrane, extracellular matrix, and collagen-related pathways. The &lt;em&gt;COL4A5, COL18A1, COL2A1&lt;/em&gt;, and &lt;em&gt;COL9A3&lt;/em&gt; genes are concurrently enriched across these pathways. A missense variant in &lt;em&gt;COL4A5&lt;/em&gt; was identified in 27 patients, and 96.3% of whom were females. Protein–protein interaction analysis demonstrated functional connections among these 4 genes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Variants in the &lt;em&gt;COL4A5, COL18A1, COL2A1, and COL9A3&lt;/em&gt; genes probably contribute to the pathogenesis of a posterior staphyloma through the disruption of collagen synthesis and basement membrane integrity. This was especially effective for the ILM and Bruch membrane. The &lt;em&gt;COL4A5&lt;/em&gt; variant may cause an ocular-predominant phenotype in heterozygous female carriers, independent of the classical features of Alport syndrome.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosure(s)&lt;/h3&gt;&lt;div&gt;The authors have no proprietary or commercial interest in any materials discussed in this artic","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101058"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}