Pub Date : 2026-03-01Epub Date: 2025-12-08DOI: 10.1016/j.xops.2025.101033
Malena Daich Varela MD, PhD , William Woof PhD , Yathusha Kumarasamy , Matthias Monhart BS , Lynn Kandakji PhD , Gunjan Naik PhD , Pallavi Bagga PhD , Alan Wilter Sousa PhD , Dun Jack Fu PhD , Catey Bunce MSc , Konstantinos Balaskas MD , Nikolas Pontikos PhD , Michel Michaelides MD
Purpose
To develop an efficient approach to estimating visual field (VF) in patients with X-linked retinitis pigmentosa (RP) based on macular OCT scans.
Design
Retrospective analysis of patients who were enrolled in a natural history study at Moorfields Eye Hospital (London, United Kingdom).
Subjects
Male patients with genetically confirmed retinitis pigmentosa GTPase regulator (RPGR)-associated RP.
Methods
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).
Main Outcome Measures
Functional parameters from static VF testing such as mean sensitivity (MS) and Hill of Vision analysis that included total volume (VTOT), volume of central 20° (V20), and volume of central 30° (V30) were predicted from EZW and EZA.
Results
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 (P = 0.00176), and MS with EZA (P = 0.0009).
Conclusions
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.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"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 , William Woof PhD , Yathusha Kumarasamy , Matthias Monhart BS , Lynn Kandakji PhD , Gunjan Naik PhD , Pallavi Bagga PhD , Alan Wilter Sousa PhD , Dun Jack Fu PhD , Catey Bunce MSc , Konstantinos Balaskas MD , Nikolas Pontikos PhD , 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<sub>TOT</sub>), volume of central 20° (V<sub>20</sub>), and volume of central 30° (V<sub>30</sub>) 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 R<sup>2</sup> (R<sup>2</sup>c) and most significant associations with MS and V<sub>20</sub>. 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}
Pub Date : 2026-03-01Epub Date: 2026-01-06DOI: 10.1016/j.xops.2025.101061
Maverick Wenhao Wong MBBS , Huanye Li BEng , Yee Shan Dan MSc , Samantha CN. Lor , Raphael Soh MBBS , Quan V. Hoang MD, PhD , Rachel S. Chong MBBS, PhD
<div><h3>Objective</h3><div>To investigate the relationship between intraocular pressure (IOP) and antiglaucoma medications on both the incidence and progression of myopic macular degeneration (MMD), posterior staphyloma and axial length (AXL) elongation in highly myopic (HM) eyes.</div></div><div><h3>Design</h3><div>A retrospective multiethnic cohort study with cross-sectional and longitudinal analyses.</div></div><div><h3>Subjects, Participants, and/or Controls</h3><div>Nine hundred eighty-eight HM eyes from 518 multi-ethnic subjects assessed at the Singapore National Eye Centre (2017–2022). Eyes with glaucoma or on existing IOP-lowering therapy were excluded from the primary analyses. Secondary cross-sectional and longitudinal analyses included eyes with glaucoma to explore medication effects.</div></div><div><h3>Methods</h3><div>Intraocular pressure was measured with noncontact tonometry. Logistic and linear regression models assessed associations between IOP and MMD/staphyloma presence and progression and AXL elongation. Multivariate analysis was performed to identify independent predictors of progression, including effects of antiglaucoma medication use.</div></div><div><h3>Main Outcome Measures</h3><div>Presence and progression of MMD and staphyloma, current AXL, and AXL elongation as determined by imaging and clinical examination. Progression was defined by changes in MMD grade, atrophic lesions, or structural staphyloma features over time.</div></div><div><h3>Results</h3><div>In nonglaucomatous eyes, IOP was not significantly associated with the presence or progression of MMD, staphyloma, or AXL (all <em>P</em> > 0.05). Across all eyes, longer AXL was correlated with earlier spectacle onset, worse visual acuity, longer anterior chamber depth, presence of tilted disc, superior peripapillary atrophy, vitreomacular traction, staphyloma, epiretinal membrane, dome- or saddle-shaped macula, and lacquer crack (<em>P</em> < 0.05). In longitudinal analyses, baseline glaucoma medication use was significantly associated with reduced AXL elongation over time (β = –0.077, <em>P</em> = 0.036), independent of IOP, whereas tilted disc and staphyloma presence predicted greater elongation (<em>P</em> < 0.05). Myopic macular degeneration and staphyloma progression were primarily associated with structural factors, including presence of sloped fovea, macular retinoschisis, epiretinal membrane, and dome- or saddle-shaped macula at baseline (<em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>Intraocular pressure was not associated with pathologic myopia-related structural changes or AXL in HM eyes. In contrast, use of antiglaucoma medications was associated with reduced AXL elongation. These findings suggest the potential for IOP-independent pharmacologic modulation of AXL in HM eyes.</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
{"title":"Associations between Intraocular Pressure or Glaucoma Medication with Axial Length and Pathologic Myopia Incidence and Progression","authors":"Maverick Wenhao Wong MBBS , Huanye Li BEng , Yee Shan Dan MSc , Samantha CN. Lor , Raphael Soh MBBS , Quan V. Hoang MD, PhD , Rachel S. Chong MBBS, PhD","doi":"10.1016/j.xops.2025.101061","DOIUrl":"10.1016/j.xops.2025.101061","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between intraocular pressure (IOP) and antiglaucoma medications on both the incidence and progression of myopic macular degeneration (MMD), posterior staphyloma and axial length (AXL) elongation in highly myopic (HM) eyes.</div></div><div><h3>Design</h3><div>A retrospective multiethnic cohort study with cross-sectional and longitudinal analyses.</div></div><div><h3>Subjects, Participants, and/or Controls</h3><div>Nine hundred eighty-eight HM eyes from 518 multi-ethnic subjects assessed at the Singapore National Eye Centre (2017–2022). Eyes with glaucoma or on existing IOP-lowering therapy were excluded from the primary analyses. Secondary cross-sectional and longitudinal analyses included eyes with glaucoma to explore medication effects.</div></div><div><h3>Methods</h3><div>Intraocular pressure was measured with noncontact tonometry. Logistic and linear regression models assessed associations between IOP and MMD/staphyloma presence and progression and AXL elongation. Multivariate analysis was performed to identify independent predictors of progression, including effects of antiglaucoma medication use.</div></div><div><h3>Main Outcome Measures</h3><div>Presence and progression of MMD and staphyloma, current AXL, and AXL elongation as determined by imaging and clinical examination. Progression was defined by changes in MMD grade, atrophic lesions, or structural staphyloma features over time.</div></div><div><h3>Results</h3><div>In nonglaucomatous eyes, IOP was not significantly associated with the presence or progression of MMD, staphyloma, or AXL (all <em>P</em> > 0.05). Across all eyes, longer AXL was correlated with earlier spectacle onset, worse visual acuity, longer anterior chamber depth, presence of tilted disc, superior peripapillary atrophy, vitreomacular traction, staphyloma, epiretinal membrane, dome- or saddle-shaped macula, and lacquer crack (<em>P</em> < 0.05). In longitudinal analyses, baseline glaucoma medication use was significantly associated with reduced AXL elongation over time (β = –0.077, <em>P</em> = 0.036), independent of IOP, whereas tilted disc and staphyloma presence predicted greater elongation (<em>P</em> < 0.05). Myopic macular degeneration and staphyloma progression were primarily associated with structural factors, including presence of sloped fovea, macular retinoschisis, epiretinal membrane, and dome- or saddle-shaped macula at baseline (<em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>Intraocular pressure was not associated with pathologic myopia-related structural changes or AXL in HM eyes. In contrast, use of antiglaucoma medications was associated with reduced AXL elongation. These findings suggest the potential for IOP-independent pharmacologic modulation of AXL in HM eyes.</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 ","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101061"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189729","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}
Pub Date : 2026-03-01Epub Date: 2025-12-24DOI: 10.1016/j.xops.2025.101042
Xiangtian Ling PhD , Yu Peng MMed , Yuzhou Zhang PhD , Charlene C. Yim FCOphthHK, FRCOphth , Hei-Nga Chan PhD , Yating Yang MMed , Qihang Sun MMed , Xiu-Juan Zhang PhD , Ka Wai Kam FCOphthHK, MSc , Wai Kit Chu DPhil , Patrick Ip MD , Alvin L. Young FRCSI, MMedSc , Christopher J. Hammond MD, FRCOphth , Stephen Kwok Wing Tsui PhD , Clement C. Tham FCOphthHK, FRCOphth , Chi Pui Pang DPhil , Li Jia Chen PhD, FCOphthHK , Jason C. Yam MD, FCOphthHK
Purpose
To identify the compositional and functional alterations in the ocular surface microbiome (OSM) which are associated with myopia in children and adolescents.
Design
A population-based, cross-sectional study.
Participants
Eight hundred forty-seven children and adolescents aged 3 to 17 years were included.
Methods
Conjunctival swab samples were collected from the participants and processed via 16S ribosomal RNA gene sequencing.
Main Outcome Measures
Microbial profiles of participants were processed with QIIME2. Alpha (species diversity) and beta diversity (community structure) metrics were calculated. Microbial functional profile was predicted using PICRUSt2.
Results
Shannon (P < 0.001) and observed (P = 0.010) indexes were different among samples from myopic eyes (n = 432), as compared with those from emmetropic (n = 214) and hyperopic (n = 201) eyes. They were correlated with spherical equivalent (Shannon P = 0.0036, observed P = 0.0129) and axial length (Shannon P = 0.0057, observed P = 0.012). Beta diversity with distinct microbial signatures was unique (P < 0.05) among the eyes with myopia (Haemophilus, Aquabacterium, Anaerococcus), emmetropia (Sphingobium, Clostridium sensu stricto 1, and Fusobacterium) and hyperopia (Streptococcus, Kocuria, and Gemella). Functional profiling found enrichment of several Kyoto Encyclopedia of Genes and Genomes pathways, including oxidative phosphorylation, in the myopic ocular surface, suggesting a distinct energy utilization pattern in the myopic microbiome.
Conclusions
This study reveals distinct compositional and functional profiles in the OSM of myopic children and adolescents. These findings demonstrate an association between refractive status and the OSM; however, causality has not been established, highlighting the need for further research.
Financial Disclosures
The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Associations between Ocular Surface Microbiome and Refractive Status in Children and Adolescents","authors":"Xiangtian Ling PhD , Yu Peng MMed , Yuzhou Zhang PhD , Charlene C. Yim FCOphthHK, FRCOphth , Hei-Nga Chan PhD , Yating Yang MMed , Qihang Sun MMed , Xiu-Juan Zhang PhD , Ka Wai Kam FCOphthHK, MSc , Wai Kit Chu DPhil , Patrick Ip MD , Alvin L. Young FRCSI, MMedSc , Christopher J. Hammond MD, FRCOphth , Stephen Kwok Wing Tsui PhD , Clement C. Tham FCOphthHK, FRCOphth , Chi Pui Pang DPhil , Li Jia Chen PhD, FCOphthHK , Jason C. Yam MD, FCOphthHK","doi":"10.1016/j.xops.2025.101042","DOIUrl":"10.1016/j.xops.2025.101042","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify the compositional and functional alterations in the ocular surface microbiome (OSM) which are associated with myopia in children and adolescents.</div></div><div><h3>Design</h3><div>A population-based, cross-sectional study.</div></div><div><h3>Participants</h3><div>Eight hundred forty-seven children and adolescents aged 3 to 17 years were included.</div></div><div><h3>Methods</h3><div>Conjunctival swab samples were collected from the participants and processed via 16S ribosomal RNA gene sequencing.</div></div><div><h3>Main Outcome Measures</h3><div>Microbial profiles of participants were processed with QIIME2. Alpha (species diversity) and beta diversity (community structure) metrics were calculated. Microbial functional profile was predicted using PICRUSt2.</div></div><div><h3>Results</h3><div>Shannon (<em>P</em> < 0.001) and observed (<em>P</em> = 0.010) indexes were different among samples from myopic eyes (n = 432), as compared with those from emmetropic (n = 214) and hyperopic (n = 201) eyes. They were correlated with spherical equivalent (Shannon <em>P</em> = 0.0036, observed <em>P</em> = 0.0129) and axial length (Shannon <em>P</em> = 0.0057, observed <em>P</em> = 0.012). Beta diversity with distinct microbial signatures was unique (<em>P</em> < 0.05) among the eyes with myopia (<em>Haemophilus</em>, <em>Aquabacterium</em>, <em>Anaerococcus</em>), emmetropia (<em>Sphingobium</em>, <em>Clostridium sensu stricto 1</em>, and <em>Fusobacterium</em>) and hyperopia (<em>Streptococcus</em>, <em>Kocuria</em>, and <em>Gemella</em>). Functional profiling found enrichment of several Kyoto Encyclopedia of Genes and Genomes pathways, including oxidative phosphorylation, in the myopic ocular surface, suggesting a distinct energy utilization pattern in the myopic microbiome.</div></div><div><h3>Conclusions</h3><div>This study reveals distinct compositional and functional profiles in the OSM of myopic children and adolescents. These findings demonstrate an association between refractive status and the OSM; however, causality has not been established, highlighting the need for further research.</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 3","pages":"Article 101042"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039783","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}
Pub Date : 2026-03-01Epub Date: 2025-12-18DOI: 10.1016/j.xops.2025.101030
Ahammed Sakir Nabil , Sina Gholami MS , Theodore Leng MD, MS , Jennifer I. Lim MD , Minhaj Nur Alam PhD
<div><h3>Purpose</h3><div>To conduct a comprehensive systematic evaluation of federated learning (FL) strategies for multi-disease retinal classification using OCT angiography (OCTA), implementing a 2-part experimental framework to establish foundational feasibility and optimize performance under realistic heterogeneous conditions while ensuring privacy preservation.</div></div><div><h3>Design</h3><div>Retrospective multi-center FL study using a systematic 2-part experimental design: (1) foundational feasibility evaluation under controlled homogeneous conditions, and (2) comprehensive optimization under realistic heterogeneous conditions using Dirichlet distribution partitioning (<em>α</em> = 0.5).</div></div><div><h3>Participants</h3><div>A total of 456 OCTA images from patients with 7 retinal pathologies, with diabetic retinopathy (31.1%) and normal cases (25.2%) comprising the majority, sourced from the public OCTA-500 data set (n = 300) and a private collection from the University of Illinois Chicago (n = 156).</div></div><div><h3>Methods</h3><div>Five FL aggregation strategies (federated averaging [FedAvg], federated proximal [FedProx], federated magnetic resonance imaging [FedMRI], federated Adagrad, and federated Yogi) were systematically evaluated across multiple optimization dimensions: 7 architecture configurations spanning vision transformers, established convolutional neural networks, and hybrid models; 5 transfer learning freezing strategies; 3 local epoch configurations (2, 5, and 10); and scalability analysis across 2, 3, and 5-client federations. Security mechanisms including differential privacy (ε = 1.0–8.0) and secure aggregation were integrated and evaluated. Performance was assessed across 3 classification scenarios: 7-class, 4-class modified, and 4-class streamlined.</div></div><div><h3>Main Outcome Measures</h3><div>Classification accuracy, receiver-operating-characteristic area under the curve (ROC-AUC), and macro-averaged F1-score with comprehensive privacy-utility analysis and computational efficiency metrics.</div></div><div><h3>Results</h3><div>Under controlled conditions, FL achieved superior performance in simplified classifications, with FedAvg, FedProx, and FedMRI reaching 72.09% accuracy versus 69.77% centralized training. Comprehensive optimization identified DenseNet121 as optimal architecture (79.55% accuracy, 89.68% ROC-AUC), with “most” freezing strategy (75% frozen layers) providing 60% training time reduction while maintaining superior performance. Federated proximal demonstrated exceptional resilience to heterogeneity (–11.7% degradation). Bonawitz secure aggregation achieved optimal privacy-utility balance (63.64% accuracy with cryptographic guarantees), whereas differential privacy maintained clinical utility under moderate constraints (ε ≈ 4–6).</div></div><div><h3>Conclusions</h3><div>This systematic evaluation establishes FL as a comprehensive solution for privacy-preserving multi-institutional OCTA-b
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Pub Date : 2026-03-01Epub Date: 2026-01-10DOI: 10.1016/j.xops.2026.101066
An Ran Ran PhD, MMed , Xiaoyan Hu MPhil , Herbert Y.H. Hui MBChB , Jiajia Dai PhD , Victor T.T. Chan MBChB , Ko Ho MBChB, PhD , Lisa W.C. Au FHKCP , Chak Fung Ng , Kaiser Sham , Chunwen Zheng MMed , Xujia Liu MMed , Qinghua He PhD , Clement C. Tham FCOphthHK , Timothy C.K. Kwok MD , Saima Hilal MD, PhD , Ching-Yu Cheng PhD, MD , Jacqueline Chua PhD , Leopold Schmetterer PhD , T.Y.Alvin Liu MD , Yih Chung Tham PhD , Carol Y. Cheung PhD, FARVO
Purpose
There has been significant progress in detecting Alzheimer's disease (AD) using retinal imaging. We developed an ensemble learning-based deep learning (DL) model, integrating different inputs from OCT for the detection of AD-dementia and early AD.
Design
A retrospective multicenter case-control study.
Participants
A total of 190 participants with AD-dementia and 623 cognitively normal controls were recruited from 2 cohorts in Hong Kong and Singapore as the training and internal validation sets. A total of 46 participants with AD-dementia, 79 participants with mild cognitive impairment (MCI), and 52 cognitively normal controls from 2 cohorts with amyloid-β status identified from positron emission tomography (PET) available in Hong Kong and Singapore as External-1 and External-2, respectively.
Methods
We developed DL models for identifying AD-dementia versus cognitively normal and also tested the proposed ensemble model for classifying MCI (symptom-based) and AD-MCI (PET-based). Inputs were generated from a commercially available OCT device (Cirrus HD-OCT, Carl Zeiss Meditec, Inc), including optic nerve head (ONH)-centered and macula-centered en face images along with retinal nerve fiber layer thickness and deviation maps, ganglion cell-inner plexiform layer thickness and deviation maps, and macular thickness map. Then, to integrate multiple algorithms and inputs simultaneously, we developed an ensemble model that integrated 2 base DL models—ONH model and the macula model, developed by OCT inputs from the ONH and macula regions, respectively—to provide a unified classification via majority voting.
Main Outcome Measures
Discriminative performance of the ensemble model for detecting AD-dementia, MCI, and AD-MCI.
Results
For detecting AD-dementia, the ensemble model achieved the area under the receiver operating characteristic curve (AUROC) of 0.943 (95% confidence interval, 0.906–0.980), 0.786 (95% confidence interval, 0.673–0.899), and 0.795 (95% confidence interval, 0.716–0.874) in the internal validation, External-1, and External-2, respectively. For detecting AD-MCI defined by PET biomarkers, the ensemble model achieved AUROCs of 0.787 (95% confidence interval, 0.643–0.931) and 0.791 (95% confidence interval, 0.694–0.888) in the External-1 and External-2, respectively.
Conclusions
Our proposed ensemble model, integrating multiple base models and inputs from OCT analysis, demonstrates strong potential for leveraging OCT imaging in detecting both AD-dementia and early-stage AD, enabling opportunistic screening for AD during ophthalmic visits.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"An Ensemble Learning Artificial Intelligence Model for Alzheimer's Disease Detection Using OCT","authors":"An Ran Ran PhD, MMed , Xiaoyan Hu MPhil , Herbert Y.H. Hui MBChB , Jiajia Dai PhD , Victor T.T. Chan MBChB , Ko Ho MBChB, PhD , Lisa W.C. Au FHKCP , Chak Fung Ng , Kaiser Sham , Chunwen Zheng MMed , Xujia Liu MMed , Qinghua He PhD , Clement C. Tham FCOphthHK , Timothy C.K. Kwok MD , Saima Hilal MD, PhD , Ching-Yu Cheng PhD, MD , Jacqueline Chua PhD , Leopold Schmetterer PhD , T.Y.Alvin Liu MD , Yih Chung Tham PhD , Carol Y. Cheung PhD, FARVO","doi":"10.1016/j.xops.2026.101066","DOIUrl":"10.1016/j.xops.2026.101066","url":null,"abstract":"<div><h3>Purpose</h3><div>There has been significant progress in detecting Alzheimer's disease (AD) using retinal imaging. We developed an ensemble learning-based deep learning (DL) model, integrating different inputs from OCT for the detection of AD-dementia and early AD.</div></div><div><h3>Design</h3><div>A retrospective multicenter case-control study.</div></div><div><h3>Participants</h3><div>A total of 190 participants with AD-dementia and 623 cognitively normal controls were recruited from 2 cohorts in Hong Kong and Singapore as the training and internal validation sets. A total of 46 participants with AD-dementia, 79 participants with mild cognitive impairment (MCI), and 52 cognitively normal controls from 2 cohorts with amyloid-β status identified from positron emission tomography (PET) available in Hong Kong and Singapore as External-1 and External-2, respectively.</div></div><div><h3>Methods</h3><div>We developed DL models for identifying AD-dementia versus cognitively normal and also tested the proposed ensemble model for classifying MCI (symptom-based) and AD-MCI (PET-based). Inputs were generated from a commercially available OCT device (Cirrus HD-OCT, Carl Zeiss Meditec, Inc), including optic nerve head (ONH)-centered and macula-centered <em>en face</em> images along with retinal nerve fiber layer thickness and deviation maps, ganglion cell-inner plexiform layer thickness and deviation maps, and macular thickness map. Then, to integrate multiple algorithms and inputs simultaneously, we developed an ensemble model that integrated 2 base DL models—ONH model and the macula model, developed by OCT inputs from the ONH and macula regions, respectively—to provide a unified classification via majority voting.</div></div><div><h3>Main Outcome Measures</h3><div>Discriminative performance of the ensemble model for detecting AD-dementia, MCI, and AD-MCI.</div></div><div><h3>Results</h3><div>For detecting AD-dementia, the ensemble model achieved the area under the receiver operating characteristic curve (AUROC) of 0.943 (95% confidence interval, 0.906–0.980), 0.786 (95% confidence interval, 0.673–0.899), and 0.795 (95% confidence interval, 0.716–0.874) in the internal validation, External-1, and External-2, respectively. For detecting AD-MCI defined by PET biomarkers, the ensemble model achieved AUROCs of 0.787 (95% confidence interval, 0.643–0.931) and 0.791 (95% confidence interval, 0.694–0.888) in the External-1 and External-2, respectively.</div></div><div><h3>Conclusions</h3><div>Our proposed ensemble model, integrating multiple base models and inputs from OCT analysis, demonstrates strong potential for leveraging OCT imaging in detecting both AD-dementia and early-stage AD, enabling opportunistic screening for AD during ophthalmic visits.</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 101066"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189726","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}
To assess the agreement between blue autofluorescence (BAF) and green autofluorescence (GAF) fundus imaging in measuring the macular hyperautofluorescent (hyperAF) ring in patients with inherited retinal diseases (IRDs).
Design
A prospective, within-subject agreement study.
Subjects
A total of 124 patients with IRD (67% with retinitis pigmentosa, 33% with cone–rod/macular dystrophies) from Moorfields Eye Hospital were included. Mean age was 36.5 years; 60% were male. Most (99%) had a genetically confirmed diagnosis.
Methods
Participants underwent BAF (Heidelberg) and GAF (Optos) imaging during the same visit. Hyperautofluorescent ring area and horizontal and vertical diameters were independently measured by 2 ophthalmologists. Agreement between imaging modalities was assessed using intraclass correlation coefficients, Pearson correlation, paired t tests, linear and mixed-effects regression, Bland–Altman plots, and 1-sided z-tests for equivalence within a ±10% margin.
Main Outcome Measures
Comparison of hyperAF ring area and diameters between BAF and GAF.
Results
Intergrader agreement was excellent (intraclass correlation coefficient: 0.93–0.98). Blue autofluorescence measured slightly larger ring areas than GAF (mean difference: 0.7 mm2, P = 0.006), while horizontal and vertical diameters were nearly equivalent (mean differences: 0.03 μm and 0.08 μm, P = 0.96 and P = 0.04, respectively). Discrepancies >10% were observed in 17% of cases in horizontal diameter, 27% of cases in vertical, and 42% of cases in area. Correlations were high (r = 0.98) for all metrics. Mixed-effects models including both eyes (n = 217) estimated that the area measured in GAF is 4.1% smaller than in BAF, the horizontal is approximately 0.5% smaller, and the vertical is around 2.2% smaller, with evidence of agreement within a ±6% margin at a 5% significance level.
Conclusions
High correlation and consistent regression slopes were seen between BAF and GAF macular hyperAF ring. These results suggest that while the 2 modalities yield broadly comparable measurements, with BAF yielding larger values, these modalities should ideally not be used interchangeably.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Assessing Agreement between Blue-Light and Green-Light Autofluorescence of Macular Hyperautofluorescent Rings in Inherited Retinal Diseases","authors":"Malena Daich Varela MD, PhD , Nancy Aychoua MD , Memuna Rashid MSc , Andre Lopes PhD , Michel Michaelides MD","doi":"10.1016/j.xops.2025.101026","DOIUrl":"10.1016/j.xops.2025.101026","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the agreement between blue autofluorescence (BAF) and green autofluorescence (GAF) fundus imaging in measuring the macular hyperautofluorescent (hyperAF) ring in patients with inherited retinal diseases (IRDs).</div></div><div><h3>Design</h3><div>A prospective, within-subject agreement study.</div></div><div><h3>Subjects</h3><div>A total of 124 patients with IRD (67% with retinitis pigmentosa, 33% with cone–rod/macular dystrophies) from Moorfields Eye Hospital were included. Mean age was 36.5 years; 60% were male. Most (99%) had a genetically confirmed diagnosis.</div></div><div><h3>Methods</h3><div>Participants underwent BAF (Heidelberg) and GAF (Optos) imaging during the same visit. Hyperautofluorescent ring area and horizontal and vertical diameters were independently measured by 2 ophthalmologists. Agreement between imaging modalities was assessed using intraclass correlation coefficients, Pearson correlation, paired <em>t</em> tests, linear and mixed-effects regression, Bland–Altman plots, and 1-sided z-tests for equivalence within a ±10% margin.</div></div><div><h3>Main Outcome Measures</h3><div>Comparison of hyperAF ring area and diameters between BAF and GAF.</div></div><div><h3>Results</h3><div>Intergrader agreement was excellent (intraclass correlation coefficient: 0.93–0.98). Blue autofluorescence measured slightly larger ring areas than GAF (mean difference: 0.7 mm<sup>2</sup>, <em>P</em> = 0.006), while horizontal and vertical diameters were nearly equivalent (mean differences: 0.03 μm and 0.08 μm, <em>P</em> = 0.96 and <em>P</em> = 0.04, respectively). Discrepancies >10% were observed in 17% of cases in horizontal diameter, 27% of cases in vertical, and 42% of cases in area. Correlations were high (<em>r</em> = 0.98) for all metrics. Mixed-effects models including both eyes (n = 217) estimated that the area measured in GAF is 4.1% smaller than in BAF, the horizontal is approximately 0.5% smaller, and the vertical is around 2.2% smaller, with evidence of agreement within a ±6% margin at a 5% significance level.</div></div><div><h3>Conclusions</h3><div>High correlation and consistent regression slopes were seen between BAF and GAF macular hyperAF ring. These results suggest that while the 2 modalities yield broadly comparable measurements, with BAF yielding larger values, these modalities should ideally not be used interchangeably.</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 3","pages":"Article 101026"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079751","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}
Pub Date : 2026-03-01Epub Date: 2026-01-05DOI: 10.1016/j.xops.2025.101060
Yunchan Hwang SM , Muhammad Usman Jamil MD , Kwang Min Woo MD , Stephanie M. Kaiser BA , Fatima Babiker MD , Philip J. Rosenfeld MD, PhD , Nadia K. Waheed MD , James G. Fujimoto PhD
Purpose
To investigate choriocapillaris (CC) blood flow speed in regions associated with hypertransmission defects (hyperTDs) in nonexudative age-related macular degeneration (AMD) using variable interscan time analysis (VISTA) OCT angiography (OCTA).
Design
Retrospective cross-sectional analysis of a prospectively collected cohort.
Subjects
Thirty-one eyes from 29 subjects with nonexudative AMD.
Methods
Patients with age-related macular degeneration were imaged using a 600 kHz A-scan rate prototype swept-source OCT with a 5 × 5 mm field of view and 5 B-scan repeats (1.25 ms interscan time). Hypertransmission defects were traced on choroidal en face projections and categorized by their greatest linear dimension (GLD): large (≥250 μm), medium (63–250 μm), and small (<63 μm). Choriocapillaris blood flow speed was quantified using VISTA, which measures OCTA signal saturation dynamics across multiple interscan times. Variable interscan time analysis flow speed (VFS) was evaluated at the macula and within hyperTDs. Choriocapillaris flow speed impairment (ΔVFS) for each hyperTD was calculated as the difference between its VFS and the macular average. To assess spatial extent, ΔVFS was assessed beyond lesion boundaries. Traditional metrics of OCTA signal and flow deficits (FDs) were also evaluated.
Main Outcome Measures
Choriocapillaris blood flow speed impairment (ΔVFS) within and around hyperTDs.
Results
The macular average CC VFS was 1.47 ± 0.34 ms–1, with no significant difference between eyes with (n = 14) and without (n = 17) hyperTDs. A total of 88 hyperTDs were analyzed: 19 large, 28 medium, and 41 small. Large hyperTDs showed significant CC flow impairment (ΔVFS = –0.37 ± 0.18 ms–1, Padjusted < 0.0001), with impairment extending 100 μm beyond lesion boundaries (Padjusted = 0.0061). Medium-sized hyperTDs demonstrated moderate impairment (ΔVFS = –0.30 ± 0.47 ms–1, Padjusted = 0.031), while small hyperTDs did not. In linear mixed-effects modeling, large and medium hyperTDs were associated with significant reductions in flow speed (–0.40 ms–1, P = 0.014; –0.31 ms–1, P = 0.030, respectively), corresponding to approximately 25% decreases from macular average. OCT angiography signal and FD metrics also detected size-dependent flow impairment.
Conclusions
Large hyperTDs in nonexudative AMD exhibit reduced CC flow speed extending beyond the lesion boundary. Longitudinal studies will investigate whether CC flow predicts onset and progression of hyperTDs.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Large Hypertransmission Defects Exhibit Choriocapillaris Flow Speed Impairment in Nonexudative Age-Related Macular Degeneration","authors":"Yunchan Hwang SM , Muhammad Usman Jamil MD , Kwang Min Woo MD , Stephanie M. Kaiser BA , Fatima Babiker MD , Philip J. Rosenfeld MD, PhD , Nadia K. Waheed MD , James G. Fujimoto PhD","doi":"10.1016/j.xops.2025.101060","DOIUrl":"10.1016/j.xops.2025.101060","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate choriocapillaris (CC) blood flow speed in regions associated with hypertransmission defects (hyperTDs) in nonexudative age-related macular degeneration (AMD) using variable interscan time analysis (VISTA) OCT angiography (OCTA).</div></div><div><h3>Design</h3><div>Retrospective cross-sectional analysis of a prospectively collected cohort.</div></div><div><h3>Subjects</h3><div>Thirty-one eyes from 29 subjects with nonexudative AMD.</div></div><div><h3>Methods</h3><div>Patients with age-related macular degeneration were imaged using a 600 kHz A-scan rate prototype swept-source OCT with a 5 × 5 mm field of view and 5 B-scan repeats (1.25 ms interscan time). Hypertransmission defects were traced on choroidal en face projections and categorized by their greatest linear dimension (GLD): large (≥250 μm), medium (63–250 μm), and small (<63 μm). Choriocapillaris blood flow speed was quantified using VISTA, which measures OCTA signal saturation dynamics across multiple interscan times. Variable interscan time analysis flow speed (VFS) was evaluated at the macula and within hyperTDs. Choriocapillaris flow speed impairment (ΔVFS) for each hyperTD was calculated as the difference between its VFS and the macular average. To assess spatial extent, ΔVFS was assessed beyond lesion boundaries. Traditional metrics of OCTA signal and flow deficits (FDs) were also evaluated.</div></div><div><h3>Main Outcome Measures</h3><div>Choriocapillaris blood flow speed impairment (ΔVFS) within and around hyperTDs.</div></div><div><h3>Results</h3><div>The macular average CC VFS was 1.47 ± 0.34 ms<sup>–1</sup>, with no significant difference between eyes with (n = 14) and without (n = 17) hyperTDs. A total of 88 hyperTDs were analyzed: 19 large, 28 medium, and 41 small. Large hyperTDs showed significant CC flow impairment (ΔVFS = –0.37 ± 0.18 ms<sup>–1</sup>, P<sub>adjusted</sub> < 0.0001), with impairment extending 100 μm beyond lesion boundaries (P<sub>adjusted</sub> = 0.0061). Medium-sized hyperTDs demonstrated moderate impairment (ΔVFS = –0.30 ± 0.47 ms<sup>–1</sup>, P<sub>adjusted</sub> = 0.031), while small hyperTDs did not. In linear mixed-effects modeling, large and medium hyperTDs were associated with significant reductions in flow speed (–0.40 ms<sup>–1</sup>, <em>P</em> = 0.014; –0.31 ms<sup>–1</sup>, <em>P</em> = 0.030, respectively), corresponding to approximately 25% decreases from macular average. OCT angiography signal and FD metrics also detected size-dependent flow impairment.</div></div><div><h3>Conclusions</h3><div>Large hyperTDs in nonexudative AMD exhibit reduced CC flow speed extending beyond the lesion boundary. Longitudinal studies will investigate whether CC flow predicts onset and progression of hyperTDs.</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 101060"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189727","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}
Pub Date : 2026-03-01Epub Date: 2026-01-07DOI: 10.1016/j.xops.2026.101065
Jack Phu MD, PhD , Henrietta Wang MPH , Jeremy C.K. Tan MD , Michael Kalloniatis MScOptom, PhD
<div><h3>Purpose</h3><div>To predict intrinsic measurement variability and reliability (any cause of data loss) in visual field (VF) results using a computer simulation model.</div></div><div><h3>Design</h3><div>Computer simulation study.</div></div><div><h3>Subjects</h3><div>One hundred thousand subjects simulated with empirical mean deviation, progression rate, variability, and reliability characteristics.</div></div><div><h3>Methods</h3><div>One hundred thousand subjects were simulated to undergo 4 VF tests per visit, 3 monthly, over 20 years (long-term condition) and 4 VF tests per visit daily over 28 days (short-term condition). Permutations of 1-4 tests per visit over 3-, 6-, and 12-monthly (long-term) and 1-, 2-, and 4-daily (short-term) review intervals were used. Visual field variabilities were estimated sequentially until 3 consecutive visits returned variabilities within 5% of each other using a rolling window. The same was applied to reliability. The last visit of the window denoted the critical time to estimating variability using the consecutive clinical criterion (TcV) and critical time to estimating reliability using the consecutive clinical criterion (TcR) estimation. Additionally, we identified the critical time at which 3 consecutive visits were within 5% of the ground truth (critical time to estimating variability using the consecutive clinical criterion and comparison with the ground truth [TgV] and critical time to estimating reliability using the consecutive clinical criterion and comparison with the ground truth [TgR]).</div></div><div><h3>Main Measures</h3><div>Critical time to estimating intrinsic variability and reliability.</div></div><div><h3>Results</h3><div>The most intensive long-term approach (4 tests/visit, 3 monthly) required a median of 6 years to reach TcV. In the long-term, most subjects arrived at TcR within 2 years, but short-term testing (even with 1 test per visit) required only 5 days of daily testing. More tests per visit and more frequent reviews shortened the critical time. Average differences between the estimated variability and reliability at TcV and TcR and their ground truth results were clinically small (within 1 decibel and 10%, respectively). Mean deviation, progression rate, and variability were significant predictors of TcV and TgV for long-term follow-up, with no clinically significant predictors for short-term variability (R<sup>2</sup> < 0.0001). Only reliability predicted TcR and TgR. Predictors had low coefficients of determination (<0.2).</div></div><div><h3>Conclusions</h3><div>Longitudinal estimates of variability are not likely achievable in clinical practice, but short-term intensive VF testing unaffected by progression can return variability and reliability rates within reasonable timeframes. We provide a framework for the effect of variability for the likelihood of detecting differences in VF results over time, given reliability rates.</div></div><div><h3>Financial Disclosu
{"title":"Predicting Variability and Reliability in Visual Field Testing: Short- and Long-Term Approaches","authors":"Jack Phu MD, PhD , Henrietta Wang MPH , Jeremy C.K. Tan MD , Michael Kalloniatis MScOptom, PhD","doi":"10.1016/j.xops.2026.101065","DOIUrl":"10.1016/j.xops.2026.101065","url":null,"abstract":"<div><h3>Purpose</h3><div>To predict intrinsic measurement variability and reliability (any cause of data loss) in visual field (VF) results using a computer simulation model.</div></div><div><h3>Design</h3><div>Computer simulation study.</div></div><div><h3>Subjects</h3><div>One hundred thousand subjects simulated with empirical mean deviation, progression rate, variability, and reliability characteristics.</div></div><div><h3>Methods</h3><div>One hundred thousand subjects were simulated to undergo 4 VF tests per visit, 3 monthly, over 20 years (long-term condition) and 4 VF tests per visit daily over 28 days (short-term condition). Permutations of 1-4 tests per visit over 3-, 6-, and 12-monthly (long-term) and 1-, 2-, and 4-daily (short-term) review intervals were used. Visual field variabilities were estimated sequentially until 3 consecutive visits returned variabilities within 5% of each other using a rolling window. The same was applied to reliability. The last visit of the window denoted the critical time to estimating variability using the consecutive clinical criterion (TcV) and critical time to estimating reliability using the consecutive clinical criterion (TcR) estimation. Additionally, we identified the critical time at which 3 consecutive visits were within 5% of the ground truth (critical time to estimating variability using the consecutive clinical criterion and comparison with the ground truth [TgV] and critical time to estimating reliability using the consecutive clinical criterion and comparison with the ground truth [TgR]).</div></div><div><h3>Main Measures</h3><div>Critical time to estimating intrinsic variability and reliability.</div></div><div><h3>Results</h3><div>The most intensive long-term approach (4 tests/visit, 3 monthly) required a median of 6 years to reach TcV. In the long-term, most subjects arrived at TcR within 2 years, but short-term testing (even with 1 test per visit) required only 5 days of daily testing. More tests per visit and more frequent reviews shortened the critical time. Average differences between the estimated variability and reliability at TcV and TcR and their ground truth results were clinically small (within 1 decibel and 10%, respectively). Mean deviation, progression rate, and variability were significant predictors of TcV and TgV for long-term follow-up, with no clinically significant predictors for short-term variability (R<sup>2</sup> < 0.0001). Only reliability predicted TcR and TgR. Predictors had low coefficients of determination (<0.2).</div></div><div><h3>Conclusions</h3><div>Longitudinal estimates of variability are not likely achievable in clinical practice, but short-term intensive VF testing unaffected by progression can return variability and reliability rates within reasonable timeframes. We provide a framework for the effect of variability for the likelihood of detecting differences in VF results over time, given reliability rates.</div></div><div><h3>Financial Disclosu","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101065"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189730","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}
Pub Date : 2026-03-01Epub Date: 2025-12-15DOI: 10.1016/j.xops.2025.101037
Jiaying Li MD, PhD , Ye Zhang MD, PhD , Zhen Cheng MD, PhD , Chunyan Qiao MD, PhD , Kai Cao MD, PhD , Minguang He MD, PhD , Ningli Wang MD, PhD
Objective
Primary angle closure disease (PACD) has long been the focus of screening, yet most cases are nonprogressive. In contrast, primary angle closure with or without glaucoma (PAC/G) poses greater risk and may deserve more attention. We aimed to compare screening indicator profiles for PACD and PAC/G, highlighting potential differences that may inform a shift in screening priorities.
Design
A population-based cross-sectional study.
Participants
Adults aged ≥35 years who completed standardized eye examinations. Only right eyes were analyzed; eyes with prior laser peripheral iridotomy were excluded.
Methods
Participants underwent gonioscopy, anterior-segment OCT (AS-OCT), and A-scan ultrasound biometry. Univariable logistic regression and multivariable elastic-net models assessed the association and discriminative performance of AS-OCT parameters for detecting PACD and PAC/G.
Main Outcome Measures
Odds ratios (ORs) and area under the receiver operator characteristic curve (AUROC) values of AS-OCT parameters for detecting PACD and PAC/G.
Results
Of the 4546 eyes analyzed, 3831 had open angles and 715 had PACD, of which 53 had PAC/G. In the univariable logistic regression analysis, the angle opening distance (AOD) at 250 μm (AOD250) and the trabecular–iris space area (TISA) at 500 μm (TISA500) were more strongly associated with PAC/G than with PACD (P < 0.05, Wald test), whereas AOD500/750 and TISA750 were not significantly different in association. Additionally, TISA750 exhibited the highest AUROC value (0.88) for detecting PACD, whereas TISA500 had the highest AUROC value (0.91) for detecting PAC/G. Higher iris curvature was significantly associated with increased odds of PACD (OR: 1250.26; 95% confidence interval [CI]: 234.52–2265.99) but not with PAC/G (P < 0.05, Wald test). In the multivariable models for detecting PAC/G, a profile characterized by lower iris curvature (OR: 0.06; 95% CI: 0.05–0.08), narrower angle width (AOD500, TISA500, and TISA750), smaller anterior chamber area and volume, and smaller pupil diameter achieved an AUROC of 0.908 (95% CI: 0.858–0.959).
Conclusions
Angle parameters closer to the scleral spur were underestimated, and curved irises were overestimated when screening for PAC/G versus PACD. Anterior-segment OCT–derived models for PAC/G screening have shown promising feasibility in population-based settings.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Differences in Screening Indicator Performance for Primary Angle Closure and Primary Angle Closure Diseases: The Handan Eye Study","authors":"Jiaying Li MD, PhD , Ye Zhang MD, PhD , Zhen Cheng MD, PhD , Chunyan Qiao MD, PhD , Kai Cao MD, PhD , Minguang He MD, PhD , Ningli Wang MD, PhD","doi":"10.1016/j.xops.2025.101037","DOIUrl":"10.1016/j.xops.2025.101037","url":null,"abstract":"<div><h3>Objective</h3><div>Primary angle closure disease (PACD) has long been the focus of screening, yet most cases are nonprogressive. In contrast, primary angle closure with or without glaucoma (PAC/G) poses greater risk and may deserve more attention. We aimed to compare screening indicator profiles for PACD and PAC/G, highlighting potential differences that may inform a shift in screening priorities.</div></div><div><h3>Design</h3><div>A population-based cross-sectional study.</div></div><div><h3>Participants</h3><div>Adults aged ≥35 years who completed standardized eye examinations. Only right eyes were analyzed; eyes with prior laser peripheral iridotomy were excluded.</div></div><div><h3>Methods</h3><div>Participants underwent gonioscopy, anterior-segment OCT (AS-OCT), and A-scan ultrasound biometry. Univariable logistic regression and multivariable elastic-net models assessed the association and discriminative performance of AS-OCT parameters for detecting PACD and PAC/G.</div></div><div><h3>Main Outcome Measures</h3><div>Odds ratios (ORs) and area under the receiver operator characteristic curve (AUROC) values of AS-OCT parameters for detecting PACD and PAC/G.</div></div><div><h3>Results</h3><div>Of the 4546 eyes analyzed, 3831 had open angles and 715 had PACD, of which 53 had PAC/G. In the univariable logistic regression analysis, the angle opening distance (AOD) at 250 μm (AOD250) and the trabecular–iris space area (TISA) at 500 μm (TISA500) were more strongly associated with PAC/G than with PACD (<em>P</em> < 0.05, Wald test), whereas AOD500/750 and TISA750 were not significantly different in association. Additionally, TISA750 exhibited the highest AUROC value (0.88) for detecting PACD, whereas TISA500 had the highest AUROC value (0.91) for detecting PAC/G. Higher iris curvature was significantly associated with increased odds of PACD (OR: 1250.26; 95% confidence interval [CI]: 234.52–2265.99) but not with PAC/G (<em>P</em> < 0.05, Wald test). In the multivariable models for detecting PAC/G, a profile characterized by lower iris curvature (OR: 0.06; 95% CI: 0.05–0.08), narrower angle width (AOD500, TISA500, and TISA750), smaller anterior chamber area and volume, and smaller pupil diameter achieved an AUROC of 0.908 (95% CI: 0.858–0.959).</div></div><div><h3>Conclusions</h3><div>Angle parameters closer to the scleral spur were underestimated, and curved irises were overestimated when screening for PAC/G versus PACD. Anterior-segment OCT–derived models for PAC/G screening have shown promising feasibility in population-based settings.</div></div><div><h3>Financial Disclosure(s)</h3><div>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 101037"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189242","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}
Pub Date : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.xops.2026.101082
Zhiqiang Ye MD, Yifan Luo MD, Muhan Zhong MSc, Zaifeng Cui PhD, Huayu Zhang MSc, Xindan Chang MSc, Xue Li PhD, Yingying Huang MD, Hao Chen MD, OD, Jinhua Bao PhD
Purpose
The aim of this study was to investigate ON/OFF pathway responses and the impact of contrast reduction in myopes and emmetropes.
Design
This was a cross-sectional study.
Subjects
Thirty-eight young adult participants aged 20 to 29 years were included. Their spherical equivalent refraction ranged from +0.75 to –5.75 diopters (D).
Methods
All participants (20 myopes, 18 emmetropes) underwent multifocal electroretinogram recording after 90 minutes of exposure to monocular diffuse (contrast reduction) conditions. The 5 experimental conditions were assessed in random order on separate days for each participant: control (no diffuse), slight peripheral diffuse (0.8 Bangerter foil, 5 mm clear center), medium peripheral diffuse (MPD) (0.4 Bangerter foil, 9 mm clear center), MPD (0.4 Bangerter foil, 5 mm clear center), and medium full-field diffuse (0.4 Bangerter foil).
Main Outcome Measures
P1- and P2-wave amplitudes, as well as the P2/P1 amplitude ratio at varying retinal eccentricities were analyzed.
Results
Compared with those of emmetropic eyes, both P1- and P2-wave amplitudes were significantly lower in myopic eyes (P1-wave: 8.25 ± 1.42 vs 10.29 ± deg/deg2, P < 0.05; P2-wave: 2.52 ± 0.79 vs 3.89 ± 1.57 nV/de g2, P < 0.01). However, the decline in P2-wave amplitude (35%) was more pronounced than the reduction in P1-wave amplitude (20%), resulting in a decrease in the P2/P1 ratio (0.30 ± 0.07 vs 0.41 ± 0.19, P < 0.05). Compared with the control condition, all the peripheral diffuse conditions increased the P2-wave amplitude and significantly increased the P2/P1 ratio (0.38∼0.41 vs 0.30, all P < 0.05) in the entire analyzed field, whereas no change was observed in the full-field diffuse condition (P > 0.05). No significant differences between the slight and medium diffuse conditions were observed (P > 0.05).
Conclusions
Peripheral contrast reduction significantly strengthened OFF-pathway responses, contributing to the restoration of ON/OFF pathway balance in myopic eyes.
Financial Disclosure(s)
The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
目的探讨近视和近视眼的ON/OFF通路反应和对比度降低的影响。这是一项横断面研究。38名年龄在20至29岁之间的年轻人被纳入研究。它们的球面等效折射范围从+0.75到-5.75屈光度(D)。方法所有参与者(20名近视眼,18名近视眼)在单眼弥散(对比度降低)条件下暴露90分钟后进行多焦视网膜电图记录。在不同的日期随机评估每个参与者的5种实验条件:对照组(无弥散),轻度周围弥散(0.8 Bangerter箔,5毫米透明中心),中度周围弥散(MPD) (0.4 Bangerter箔,9毫米透明中心),MPD (0.4 Bangerter箔,5毫米透明中心)和中度全场弥散(0.4 Bangerter箔)。分析不同视网膜偏心率下的resp1和P2波幅值,以及P2/P1波幅比。结果近视眼的P1波和p2波波幅均明显低于正视眼(P1波:8.25±1.42 vs 10.29±deg/deg2, P < 0.05; p2波:2.52±0.79 vs 3.89±1.57 nV/ deg2, P < 0.01)。但P2波幅下降(35%)比P1波幅下降(20%)更为明显,导致P2/P1比值下降(0.30±0.07 vs 0.41±0.19,P < 0.05)。与对照组相比,所有外围扩散条件均增加了整个分析场的P2波振幅,显著增加了P2/P1比值(0.38 ~ 0.41 vs 0.30,均P <; 0.05),而全场扩散条件未见变化(P > 0.05)。轻度弥散与中度弥散无显著性差异(P > 0.05)。结论外周对比度降低显著增强了OFF通路反应,有助于恢复近视眼的ON/OFF通路平衡。财务披露作者在本文中讨论的任何材料中没有/作者没有专有或商业利益。
{"title":"Optically Induced Peripheral Contrast Reduction Restores ON/OFF Pathway Balance in Myopic Eyes","authors":"Zhiqiang Ye MD, Yifan Luo MD, Muhan Zhong MSc, Zaifeng Cui PhD, Huayu Zhang MSc, Xindan Chang MSc, Xue Li PhD, Yingying Huang MD, Hao Chen MD, OD, Jinhua Bao PhD","doi":"10.1016/j.xops.2026.101082","DOIUrl":"10.1016/j.xops.2026.101082","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this study was to investigate ON/OFF pathway responses and the impact of contrast reduction in myopes and emmetropes.</div></div><div><h3>Design</h3><div>This was a cross-sectional study.</div></div><div><h3>Subjects</h3><div>Thirty-eight young adult participants aged 20 to 29 years were included. Their spherical equivalent refraction ranged from +0.75 to –5.75 diopters (D).</div></div><div><h3>Methods</h3><div>All participants (20 myopes, 18 emmetropes) underwent multifocal electroretinogram recording after 90 minutes of exposure to monocular diffuse (contrast reduction) conditions. The 5 experimental conditions were assessed in random order on separate days for each participant: control (no diffuse), slight peripheral diffuse (0.8 Bangerter foil, 5 mm clear center), medium peripheral diffuse (MPD) (0.4 Bangerter foil, 9 mm clear center), MPD (0.4 Bangerter foil, 5 mm clear center), and medium full-field diffuse (0.4 Bangerter foil).</div></div><div><h3>Main Outcome Measures</h3><div>P1- and P2-wave amplitudes, as well as the P2/P1 amplitude ratio at varying retinal eccentricities were analyzed.</div></div><div><h3>Results</h3><div>Compared with those of emmetropic eyes, both P1- and P2-wave amplitudes were significantly lower in myopic eyes (P1-wave: 8.25 ± 1.42 vs 10.29 ± deg/deg<sup>2</sup>, <em>P</em> < 0.05; P2-wave: 2.52 ± 0.79 vs 3.89 ± 1.57 nV/de g<sup>2</sup>, <em>P</em> < 0.01). However, the decline in P2-wave amplitude (35%) was more pronounced than the reduction in P1-wave amplitude (20%), resulting in a decrease in the P2/P1 ratio (0.30 ± 0.07 vs 0.41 ± 0.19, <em>P</em> < 0.05). Compared with the control condition, all the peripheral diffuse conditions increased the P2-wave amplitude and significantly increased the P2/P1 ratio (0.38∼0.41 vs 0.30, all <em>P</em> < 0.05) in the entire analyzed field, whereas no change was observed in the full-field diffuse condition (<em>P</em> > 0.05). No significant differences between the slight and medium diffuse conditions were observed (<em>P</em> > 0.05).</div></div><div><h3>Conclusions</h3><div>Peripheral contrast reduction significantly strengthened OFF-pathway responses, contributing to the restoration of ON/OFF pathway balance in myopic eyes.</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 101082"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146190129","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}