Pub Date : 2025-12-13DOI: 10.1016/j.xops.2025.101029
John D. Jackson MD , Mani K. Woodward MCR , David A. Sutter , Aaron S. Coyner PhD , Carol X. Wang , Susan R. Ostmo MS , Michael F. Chiang MD, MA , Yali Jia PhD , David Huang MD, PhD , Yifan Jian PhD , J. Peter Campbell MD, MPH , Benjamin K. Young MD, MS
Objective or Purpose
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.
Design
Cross-sectional study.
Subjects
Twenty-five infants with a birth weight <1500 g or gestational age <31 weeks were scanned using a portable, handheld, swept-source UWF-OCT device.
Methods, Intervention, or Testing
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.
Main Outcome Measures
The Dice similarity coefficient (DSC) was used to assess B-scan and en face segmentations.
Results
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.
Conclusions
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.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Automated Feature Segmentation of Ultra-Widefield OCT Images","authors":"John D. Jackson MD , Mani K. Woodward MCR , David A. Sutter , Aaron S. Coyner PhD , Carol X. Wang , Susan R. Ostmo MS , Michael F. Chiang MD, MA , Yali Jia PhD , David Huang MD, PhD , Yifan Jian PhD , J. Peter Campbell MD, MPH , 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 <1500 g or gestational age <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":"2025-12-13","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}
Pub Date : 2025-12-12DOI: 10.1016/j.xops.2025.101035
Joseph P.M. Blair PhD , Robyn H. Guymer MBBS, PhD , Alicja Krzemińska-Ściga MSc , Sandro De Zanet PhD , Carlos Ciller PhD , Stefanos Apostolopoulos PhD , Zhichao Wu BAppSc(Optom), PhD
Purpose
To examine the association between the loss of the OCT outer retinal bands and deep visual sensitivity losses quantified by defect-mapping microperimetry (DMP).
Design
Cross-sectional study.
Participants
Fifty individuals with geographic atrophy (GA) secondary to age-related macular degeneration.
Methods
All participants underwent DMP testing—a strategy optimized to quantify the spatial extent of deep visual sensitivity losses through single presentations of 10 decibel stimuli—with 208 locations sampled within the central 8° radius region. Participants also underwent OCT and fundus autofluorescence (FAF) imaging. OCT scans were automatically segmented to detect regions of retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss, and FAF images were manually annotated for GA. The extent of these parameters in the central 8° radius region where DMP testing was performed, and at each individual test location, was derived through image coregistration for evaluating structure-function associations.
Main Outcome Measures
Global structure-function correlation between the proportion of locations missed on DMP testing and the extent of loss of the structural parameters based on Spearman rank correlation coefficient (ρ), and spatial agreement between the presence of structural changes and missed stimuli on DMP testing at individual test locations based on the Dice similarity coefficient (DSC).
Results
There were strong global structure-function correlations based on loss of the OCT outer retinal bands (ρ = 0.85–0.86), similar to what was seen with FAF-defined GA (ρ = 0.89; P ≥ 0.326). However, the spatial agreement between OCT-defined EZ and ELM loss with missed stimuli on DMP testing (DSC = 0.64 for both) was higher than that seen with RPE loss (DSC = 0.60) and FAF-defined GA (DSC = 0.62; P = 0.008 for both), but the structure-function spatial agreement was similar between RPE loss and FAF-defined GA (P = 0.152).
Conclusions
Spatial agreement with pointwise deep visual sensitivity losses was comparable based on OCT-defined RPE loss and FAF-defined GA, but higher based on EZ and ELM loss. These findings confirm the expected functional relevance of these automatically derived OCT-defined parameters and support their utility as tools for monitoring GA progression.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Geographic Atrophy Structure-Function Relationships Based on Loss of OCT Outer Retinal Bands and Fundus Autofluorescence","authors":"Joseph P.M. Blair PhD , Robyn H. Guymer MBBS, PhD , Alicja Krzemińska-Ściga MSc , Sandro De Zanet PhD , Carlos Ciller PhD , Stefanos Apostolopoulos PhD , Zhichao Wu BAppSc(Optom), PhD","doi":"10.1016/j.xops.2025.101035","DOIUrl":"10.1016/j.xops.2025.101035","url":null,"abstract":"<div><h3>Purpose</h3><div>To examine the association between the loss of the OCT outer retinal bands and deep visual sensitivity losses quantified by defect-mapping microperimetry (DMP).</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Participants</h3><div>Fifty individuals with geographic atrophy (GA) secondary to age-related macular degeneration.</div></div><div><h3>Methods</h3><div>All participants underwent DMP testing—a strategy optimized to quantify the spatial extent of deep visual sensitivity losses through single presentations of 10 decibel stimuli—with 208 locations sampled within the central 8° radius region. Participants also underwent OCT and fundus autofluorescence (FAF) imaging. OCT scans were automatically segmented to detect regions of retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss, and FAF images were manually annotated for GA. The extent of these parameters in the central 8° radius region where DMP testing was performed, and at each individual test location, was derived through image coregistration for evaluating structure-function associations.</div></div><div><h3>Main Outcome Measures</h3><div>Global structure-function correlation between the proportion of locations missed on DMP testing and the extent of loss of the structural parameters based on Spearman rank correlation coefficient (ρ), and spatial agreement between the presence of structural changes and missed stimuli on DMP testing at individual test locations based on the Dice similarity coefficient (DSC).</div></div><div><h3>Results</h3><div>There were strong global structure-function correlations based on loss of the OCT outer retinal bands (ρ = 0.85–0.86), similar to what was seen with FAF-defined GA (ρ = 0.89; <em>P</em> ≥ 0.326). However, the spatial agreement between OCT-defined EZ and ELM loss with missed stimuli on DMP testing (DSC = 0.64 for both) was higher than that seen with RPE loss (DSC = 0.60) and FAF-defined GA (DSC = 0.62; <em>P</em> = 0.008 for both), but the structure-function spatial agreement was similar between RPE loss and FAF-defined GA (<em>P</em> = 0.152).</div></div><div><h3>Conclusions</h3><div>Spatial agreement with pointwise deep visual sensitivity losses was comparable based on OCT-defined RPE loss and FAF-defined GA, but higher based on EZ and ELM loss. These findings confirm the expected functional relevance of these automatically derived OCT-defined parameters and support their utility as tools for monitoring GA progression.</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 101035"},"PeriodicalIF":4.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079754","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 : 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":"2025-12-08","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 : 2025-12-08DOI: 10.1016/j.xops.2025.101031
Chang Liu MD , Hong Chang Tan MBBS, PhD , Mingyi Yu MD , Isabelle Xin Yu Lee MSc , Ching-Yu Cheng MD, PhD , Yu-Chi Liu MD, PhD
Purpose
To investigate the association among corneal nerves, ocular surface, and renal function in diabetes, and to compare these variables in patients with and without chronic diabetic kidney disease (DKD).
Design
Cross-sectional study.
Participants
This study included 538 patients with type 2 diabetes.
Methods
All subjects received renal function tests, in vivo confocal microscopy examinations for corneal nerves, epithelial and immune cells, as well as ocular surface subjective and objective assessments. Univariable and multivariable regression analyses were used to determine the relationship between corneal nerve variables and renal function parameters. Multivariable logistic regression was performed to examine factors that were associated with DKD.
Main Outcome Measures
The association between corneal nerve metrics and renal function parameters.
Results
After adjusting for potential confounders, lower corneal nerve fiber density (CNFD) was significantly associated with higher urine albumin (P = 0.019), and higher corneal nerve fiber width was significantly associated with higher urine albumin and higher urine albumin-creatinine ratio (P < 0.001 and P = 0.001, respectively). Corneal nerve fiber length and width were significantly associated with DKD (P = 0.028 and P = 0.025, respectively). Compared with the non-DKD group, patients with DKD had significantly lower CNFD, length, area, and fractal dimension, as well as increased width, decreased epithelial cell density and count, and larger epithelial cell size (all P < 0.05). Patients with DKD presented with significantly lower Schirmer value and tear break-up time, and increased corneal staining and Ocular Surface Disease Index score than non-DKD patients (all P < 0.05).
Conclusions
In diabetes, the impairment of corneal nerves is associated with the deterioration of renal function. Patients who have poor corneal nerve status are at risk of DKD, and patients who have DKD should be examined for corneal neuropathy.
Financial Disclosure(s)
The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"The Association among Corneal Nerve Metrics, Ocular Surface Integrity, and Renal Function in Type 2 Diabetes","authors":"Chang Liu MD , Hong Chang Tan MBBS, PhD , Mingyi Yu MD , Isabelle Xin Yu Lee MSc , Ching-Yu Cheng MD, PhD , Yu-Chi Liu MD, PhD","doi":"10.1016/j.xops.2025.101031","DOIUrl":"10.1016/j.xops.2025.101031","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association among corneal nerves, ocular surface, and renal function in diabetes, and to compare these variables in patients with and without chronic diabetic kidney disease (DKD).</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Participants</h3><div>This study included 538 patients with type 2 diabetes.</div></div><div><h3>Methods</h3><div>All subjects received renal function tests, in vivo confocal microscopy examinations for corneal nerves, epithelial and immune cells, as well as ocular surface subjective and objective assessments. Univariable and multivariable regression analyses were used to determine the relationship between corneal nerve variables and renal function parameters. Multivariable logistic regression was performed to examine factors that were associated with DKD.</div></div><div><h3>Main Outcome Measures</h3><div>The association between corneal nerve metrics and renal function parameters.</div></div><div><h3>Results</h3><div>After adjusting for potential confounders, lower corneal nerve fiber density (CNFD) was significantly associated with higher urine albumin (<em>P</em> = 0.019), and higher corneal nerve fiber width was significantly associated with higher urine albumin and higher urine albumin-creatinine ratio (<em>P</em> < 0.001 and <em>P</em> = 0.001, respectively). Corneal nerve fiber length and width were significantly associated with DKD (<em>P</em> = 0.028 and <em>P</em> = 0.025, respectively). Compared with the non-DKD group, patients with DKD had significantly lower CNFD, length, area, and fractal dimension, as well as increased width, decreased epithelial cell density and count, and larger epithelial cell size (all <em>P</em> < 0.05). Patients with DKD presented with significantly lower Schirmer value and tear break-up time, and increased corneal staining and Ocular Surface Disease Index score than non-DKD patients (all <em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>In diabetes, the impairment of corneal nerves is associated with the deterioration of renal function. Patients who have poor corneal nerve status are at risk of DKD, and patients who have DKD should be examined for corneal neuropathy.</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 2","pages":"Article 101031"},"PeriodicalIF":4.6,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976577","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 : 2025-12-06DOI: 10.1016/j.xops.2025.101032
Mariella Saludares , Zachary Wennberg-Smith , Gala Beykin MD , Tasneem Z. Khatib MD, PhD , Mariana Nunez MD , QianQian Wang MD , Adriana Di Polo PhD , Jeffrey L. Goldberg MD, PhD
Purpose
Insulin is neuroprotective in mouse and nonhuman primate models of glaucoma. Here we evaluate the safety and efficacy of topical insulin in human patients with glaucoma.
Methods
This prospective study of once-daily topical insulin for glaucoma was conducted in 2 parts: an open-label dose escalation phase evaluating low (100 units/mL) and high doses (500 units/mL), followed by a randomized masked trial comparing low- and high-dose topical insulin. The worse-affected eye served as the study eye while the contralateral eye served as a control. The primary endpoint was safety and tolerability, monitored by recording adverse events (AEs), intraocular pressure, and serum blood glucose and potassium levels. The secondary endpoints included structural and functional testing including visual acuity, 24-2 Humphrey visual field (HVF), OCT, and macular and peripapillary flavoprotein fluorescence (FPF).
Results
Safety and tolerability were favorable for topical insulin at both doses, with no serious AEs. The most frequent AE was transient stinging, resolving almost immediately after application to the study eyes. Blood glucose levels remained consistently stable before and after insulin administration for all groups. In group 3, 5 of 15 study eyes showed an increase of average retinal nerve fiber layer (RNFL) thickness by ≥5 μm, compared with 0 of 12 fellow eyes from baseline to the 1-month visit (P = 0.0476). On average, study eyes showed a larger increase in RNFL thickness compared with fellow eyes (1.11 μm in fellow eyes vs. 2.50 μm in study eyes) with no evidence of cystoid edema, and no difference detected between the 2 dose levels. The RNFL increase reversed to baseline by 1 month after cessation of insulin treatment. There were no changes in HVF or FPF during a 4-week administration period.
Conclusions
The application of topical insulin proved safe and well-tolerated among patients with glaucoma. Notably, 1 month of topical insulin led to a significant, reversible increase in RNFL thickness, indicating evidence for pharmacodynamic effect at the retina after topical delivery. These data support study initiation to evaluate topical insulin's neuroprotective or neuroenhancement effects.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"A Phase I Randomized Trial of Topical Insulin for Glaucoma: Safety and Efficacy Outcomes","authors":"Mariella Saludares , Zachary Wennberg-Smith , Gala Beykin MD , Tasneem Z. Khatib MD, PhD , Mariana Nunez MD , QianQian Wang MD , Adriana Di Polo PhD , Jeffrey L. Goldberg MD, PhD","doi":"10.1016/j.xops.2025.101032","DOIUrl":"10.1016/j.xops.2025.101032","url":null,"abstract":"<div><h3>Purpose</h3><div>Insulin is neuroprotective in mouse and nonhuman primate models of glaucoma. Here we evaluate the safety and efficacy of topical insulin in human patients with glaucoma.</div></div><div><h3>Methods</h3><div>This prospective study of once-daily topical insulin for glaucoma was conducted in 2 parts: an open-label dose escalation phase evaluating low (100 units/mL) and high doses (500 units/mL), followed by a randomized masked trial comparing low- and high-dose topical insulin. The worse-affected eye served as the study eye while the contralateral eye served as a control. The primary endpoint was safety and tolerability, monitored by recording adverse events (AEs), intraocular pressure, and serum blood glucose and potassium levels. The secondary endpoints included structural and functional testing including visual acuity, 24-2 Humphrey visual field (HVF), OCT, and macular and peripapillary flavoprotein fluorescence (FPF).</div></div><div><h3>Results</h3><div>Safety and tolerability were favorable for topical insulin at both doses, with no serious AEs. The most frequent AE was transient stinging, resolving almost immediately after application to the study eyes. Blood glucose levels remained consistently stable before and after insulin administration for all groups. In group 3, 5 of 15 study eyes showed an increase of average retinal nerve fiber layer (RNFL) thickness by ≥5 μm, compared with 0 of 12 fellow eyes from baseline to the 1-month visit (<em>P</em> = 0.0476). On average, study eyes showed a larger increase in RNFL thickness compared with fellow eyes (1.11 μm in fellow eyes vs. 2.50 μm in study eyes) with no evidence of cystoid edema, and no difference detected between the 2 dose levels. The RNFL increase reversed to baseline by 1 month after cessation of insulin treatment. There were no changes in HVF or FPF during a 4-week administration period.</div></div><div><h3>Conclusions</h3><div>The application of topical insulin proved safe and well-tolerated among patients with glaucoma. Notably, 1 month of topical insulin led to a significant, reversible increase in RNFL thickness, indicating evidence for pharmacodynamic effect at the retina after topical delivery. These data support study initiation to evaluate topical insulin's neuroprotective or neuroenhancement effects.</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 2","pages":"Article 101032"},"PeriodicalIF":4.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976574","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 : 2025-12-06DOI: 10.1016/j.xops.2025.101034
Fares Antaki MDCM , David Mikhail MSc , Daniel Milad MD , Danny A. Mammo MD , Sumit Sharma MD , Sunil K. Srivastava MD , Bing Yu Chen MDCM , Samir Touma MDCM , Mertcan Sevgi MD , Jonathan El-Khoury MD , Pearse A. Keane MD , Qingyu Chen PhD , Yih Chung Tham PhD , Renaud Duval MD
<div><h3>Purpose</h3><div>Novel large language models (LLMs) such as Generative Pretrained Transformer-5 (GPT-5) integrate advanced reasoning capabilities that may enhance performance on complex medical question-answering tasks. For this latest generation of reasoning models, the configurations that maximize both accuracy and cost-efficiency have yet to be established. Our objective was to evaluate the performance and cost-accuracy trade-offs of OpenAI’s GPT-5 compared with previous generation LLMs on ophthalmic question answering.</div></div><div><h3>Design</h3><div>Evaluation of diagnostic test or technology.</div></div><div><h3>Participants</h3><div>Generative Pretrained Transformer-5 is a publicly available LLM.</div></div><div><h3>Methods</h3><div>In August 2025, 12 configurations of OpenAI’s GPT-5 series (3 model tiers across 4 reasoning effort settings) were evaluated alongside o1-high, o3-high, and GPT-4o, using 260 closed-access multiple-choice questions from the American Academy of Ophthalmology Basic Clinical Science Course data set. The study did not include human participants.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome was accuracy on the 260-item ophthalmology multiple-choice question set for each model configuration. The secondary outcomes included head-to-head ranking of configurations using a Bradley–Terry model applied to paired win/loss comparisons of answer accuracy, and evaluation of generated natural language rationales using a reference-anchored, pairwise LLM-as-a-judge framework. Additional analyses assessed the accuracy-cost trade-off by calculating mean per-question cost from token usage and identifying Pareto-efficient configurations.</div></div><div><h3>Results</h3><div>The configuration GPT-5-high achieved the highest accuracy (0.965; 95% confidence interval [CI], 0.942–0.985), significantly outperforming all GPT-5-nano variants (<em>P</em> < 0.001), o1-high (<em>P</em> = 0.04), and GPT-4o (<em>P</em> < 0.001), but not o3-high (0.958; 95% CI, 0.931–0.981). The configuration GPT-5-high ranked first in accuracy (1.66x stronger than o3-high) and rationale quality (1.11x stronger than o3-high), as judged by a reference-anchored LLM-as-a-judge autograder. Cost-accuracy analysis identified multiple GPT-5 configurations on the Pareto frontier, with GPT-5-mini-low providing the most optimal low-cost, high-performance configuration.</div></div><div><h3>Conclusions</h3><div>This study benchmarks the GPT-5 series on a high-quality ophthalmology question-answering data set, demonstrating that GPT-5 with high reasoning effort achieved near-perfect accuracy and outperformed prior reasoning LLMs. This study also introduces an autograder framework for scalable, automated evaluation of LLM-generated answers against reference standards in ophthalmology.</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 t
{"title":"Performance of GPT-5 Frontier Models in Ophthalmology Question Answering","authors":"Fares Antaki MDCM , David Mikhail MSc , Daniel Milad MD , Danny A. Mammo MD , Sumit Sharma MD , Sunil K. Srivastava MD , Bing Yu Chen MDCM , Samir Touma MDCM , Mertcan Sevgi MD , Jonathan El-Khoury MD , Pearse A. Keane MD , Qingyu Chen PhD , Yih Chung Tham PhD , Renaud Duval MD","doi":"10.1016/j.xops.2025.101034","DOIUrl":"10.1016/j.xops.2025.101034","url":null,"abstract":"<div><h3>Purpose</h3><div>Novel large language models (LLMs) such as Generative Pretrained Transformer-5 (GPT-5) integrate advanced reasoning capabilities that may enhance performance on complex medical question-answering tasks. For this latest generation of reasoning models, the configurations that maximize both accuracy and cost-efficiency have yet to be established. Our objective was to evaluate the performance and cost-accuracy trade-offs of OpenAI’s GPT-5 compared with previous generation LLMs on ophthalmic question answering.</div></div><div><h3>Design</h3><div>Evaluation of diagnostic test or technology.</div></div><div><h3>Participants</h3><div>Generative Pretrained Transformer-5 is a publicly available LLM.</div></div><div><h3>Methods</h3><div>In August 2025, 12 configurations of OpenAI’s GPT-5 series (3 model tiers across 4 reasoning effort settings) were evaluated alongside o1-high, o3-high, and GPT-4o, using 260 closed-access multiple-choice questions from the American Academy of Ophthalmology Basic Clinical Science Course data set. The study did not include human participants.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome was accuracy on the 260-item ophthalmology multiple-choice question set for each model configuration. The secondary outcomes included head-to-head ranking of configurations using a Bradley–Terry model applied to paired win/loss comparisons of answer accuracy, and evaluation of generated natural language rationales using a reference-anchored, pairwise LLM-as-a-judge framework. Additional analyses assessed the accuracy-cost trade-off by calculating mean per-question cost from token usage and identifying Pareto-efficient configurations.</div></div><div><h3>Results</h3><div>The configuration GPT-5-high achieved the highest accuracy (0.965; 95% confidence interval [CI], 0.942–0.985), significantly outperforming all GPT-5-nano variants (<em>P</em> < 0.001), o1-high (<em>P</em> = 0.04), and GPT-4o (<em>P</em> < 0.001), but not o3-high (0.958; 95% CI, 0.931–0.981). The configuration GPT-5-high ranked first in accuracy (1.66x stronger than o3-high) and rationale quality (1.11x stronger than o3-high), as judged by a reference-anchored LLM-as-a-judge autograder. Cost-accuracy analysis identified multiple GPT-5 configurations on the Pareto frontier, with GPT-5-mini-low providing the most optimal low-cost, high-performance configuration.</div></div><div><h3>Conclusions</h3><div>This study benchmarks the GPT-5 series on a high-quality ophthalmology question-answering data set, demonstrating that GPT-5 with high reasoning effort achieved near-perfect accuracy and outperformed prior reasoning LLMs. This study also introduces an autograder framework for scalable, automated evaluation of LLM-generated answers against reference standards in ophthalmology.</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 t","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101034"},"PeriodicalIF":4.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925826","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 : 2025-12-03DOI: 10.1016/j.xops.2025.101027
Usha Chakravarthy MD, PhD , Lajos Csincsik , Kelvin Y.C. Teo MD, PhD , Marion R. Munk MD , Dilraj S. Grewal MD , Robyn H. Guymer MD , Glenn J. Jaffe MD , Tunde Peto MD , SriniVas R. Sadda MD , Giovanni Staurenghi MD , Chui M.G. Cheung MD
Purpose
To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow.
Design
Systematic discussion and grading exercise assessing multiple imaging modalities.
Participants
Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society.
Methods
An international panel assessed the advantages and limitations of 5 imaging modalities—color fundus photography (CFP), fluorescein angiography (FA), spectral domain OCT (SD-OCT), near-infrared reflectance, and fundus autofluorescence—for detecting fibrosis in nAMD. A structured debate was followed by 2 online, masked image grading surveys. Sensitivity, specificity, and predictive accuracy of each modality, alone and in combination, were determined. Intergrader agreement was calculated. Imaging features were also correlated with histology in a nonhuman primate laser model. Based on consensus discussions at 2 in-person meetings and survey results, a 2-step diagnostic approach using SD-OCT as the primary modality was proposed.
Main Outcome Measures
Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD.
Results
Among the 5 modalities, SD-OCT was considered essential by all workgroup members. Hyperreflective material on OCT was unanimously identified as a key indicator of fibrosis. However, its limited specificity was acknowledged. In 2 masked grading exercises, SD-OCT showed the highest sensitivity (0.88 and 0.84) but only moderate specificity (0.56 and 0.57). The area under the curve (AUC) for SD-OCT was 0.72 and 0.70. A 2-step strategy combining SD-OCT with CFP or FA improved diagnostic accuracy. Hyperreflective material was defined as material with reflectivity equal to or greater than normal retinal pigment epithelium (RPE), well-defined margins, RPE disruption, and a laminated appearance. Corresponding CFP findings included well-defined yellow/white/gray subretinal lesions, and FA findings included early blocked fluorescence and late staining. This 2-step approach increased AUC to 0.85, with sensitivity of 0.83 and specificity of 0.87.
Conclusions
The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Standardization of Imaging Criteria for Detecting Macular Fibrosis in Neovascular Age-Related Macular Degeneration","authors":"Usha Chakravarthy MD, PhD , Lajos Csincsik , Kelvin Y.C. Teo MD, PhD , Marion R. Munk MD , Dilraj S. Grewal MD , Robyn H. Guymer MD , Glenn J. Jaffe MD , Tunde Peto MD , SriniVas R. Sadda MD , Giovanni Staurenghi MD , Chui M.G. Cheung MD","doi":"10.1016/j.xops.2025.101027","DOIUrl":"10.1016/j.xops.2025.101027","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow.</div></div><div><h3>Design</h3><div>Systematic discussion and grading exercise assessing multiple imaging modalities.</div></div><div><h3>Participants</h3><div>Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society.</div></div><div><h3>Methods</h3><div>An international panel assessed the advantages and limitations of 5 imaging modalities—color fundus photography (CFP), fluorescein angiography (FA), spectral domain OCT (SD-OCT), near-infrared reflectance, and fundus autofluorescence—for detecting fibrosis in nAMD. A structured debate was followed by 2 online, masked image grading surveys. Sensitivity, specificity, and predictive accuracy of each modality, alone and in combination, were determined. Intergrader agreement was calculated. Imaging features were also correlated with histology in a nonhuman primate laser model. Based on consensus discussions at 2 in-person meetings and survey results, a 2-step diagnostic approach using SD-OCT as the primary modality was proposed.</div></div><div><h3>Main Outcome Measures</h3><div>Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD.</div></div><div><h3>Results</h3><div>Among the 5 modalities, SD-OCT was considered essential by all workgroup members. Hyperreflective material on OCT was unanimously identified as a key indicator of fibrosis. However, its limited specificity was acknowledged. In 2 masked grading exercises, SD-OCT showed the highest sensitivity (0.88 and 0.84) but only moderate specificity (0.56 and 0.57). The area under the curve (AUC) for SD-OCT was 0.72 and 0.70. A 2-step strategy combining SD-OCT with CFP or FA improved diagnostic accuracy. Hyperreflective material was defined as material with reflectivity equal to or greater than normal retinal pigment epithelium (RPE), well-defined margins, RPE disruption, and a laminated appearance. Corresponding CFP findings included well-defined yellow/white/gray subretinal lesions, and FA findings included early blocked fluorescence and late staining. This 2-step approach increased AUC to 0.85, with sensitivity of 0.83 and specificity of 0.87.</div></div><div><h3>Conclusions</h3><div>The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis.</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 2","pages":"Article 101027"},"PeriodicalIF":4.6,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976573","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 : 2025-12-02DOI: 10.1016/j.xops.2025.101028
Sairi Zhang MD , Thomas F. Saunders OD , Karl G. Csaky MD , Elvira Agrón MS , Tiarnán D.L. Keenan BM BCh, PhD , Emily Y. Chew MD , Barbara A. Blodi MD , Amitha Domalpally MD, PhD
Purpose
To investigate the natural history of macular tissue preservation in geographic atrophy (GA) by evaluating the relationship between the macular tissue integrity index (MTII) and best-corrected visual acuity (BCVA) over time.
Design
Post hoc analysis of Age-Related Eye Disease Study 2 (AREDS2), a multi-center, randomized clinical trial.
Participants
Participants from the AREDS2 fundus autofluorescence ancillary study with nonsubfoveal GA.
Methods
Areas of GA were segmented by a deep learning algorithm and verified by expert graders. Macular tissue integrity index was defined as the percentage of the macula without GA within the central 1-mm and 3-mm circles. Baseline associations with BCVA were assessed, and longitudinal analyses evaluated GA progression, MTII loss, and BCVA decline over time.
Main Outcome Measures
Geographic atrophy area, MTII, and BCVA.
Results
Two hundred forty-three eyes (194 participants) were included. The median follow-up was 2 years. At baseline, the mean GA area was 1.8 mm2 (standard deviation 2.7), and the growth rate was 1.3 mm2/year. Baseline mean MTII in the 1-mm zone was 95.2% (standard deviation 9.1) with a decrease of 5.4%/year, and 87.3% (standard deviation 14.5) in the 3-mm zone with a decrease of 6.7%/year. Baseline mean BCVA was 76.4 letters (standard deviation 11.8; Snellen equivalent 20/30) with a 1.5-letter loss/year. Baseline MTII showed significant correlations with BCVA (1 mm: r = 0.17, P = 0.01; 3 mm: r = 0.14, P = 0.03), while GA area was not significantly associated with BCVA (r = –0.02, P = 0.71). Multivariable analysis showed that MTII in the 1-mm and 3-mm zones was associated with visual loss (both P < 0.0001). When eyes were stratified by MTII decline rate (stable/moderate/rapid), those in the rapid group showed numerically greater vision loss and GA growth.
Conclusions
This study characterizes the natural history of central macular preservation in GA using MTII. Results show moderate but significant associations with BCVA cross-sectionally and longitudinally. These findings suggest that MTII may offer complementary functional context for evaluating disease progression in GA, warranting further validation in clinical trial settings.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的通过评价黄斑组织完整性指数（MTII）与最佳矫正视力（BCVA）随时间变化的关系，探讨地理萎缩（GA）患者黄斑组织保存的自然历史。设计对年龄相关性眼病研究2 （AREDS2）进行事后分析，这是一项多中心随机临床试验。非中央凹下GA的AREDS2眼底自体荧光辅助研究的参与者。方法采用深度学习算法对遗传算法进行区域分割，并进行专家评分验证。黄斑组织完整性指数定义为中心1-mm和3-mm圆圈内无GA的黄斑的百分比。评估基线与BCVA的相关性，纵向分析评估GA进展、MTII损失和BCVA随时间的下降。主要观察指标：地理萎缩面积、MTII和BCVA。结果共纳入234只眼（194例）。中位随访时间为2年。基线时，平均GA面积为1.8 mm2（标准差为2.7），增长率为1.3 mm2/年。基线平均MTII在1 mm区域为95.2%（标准差9.1），下降5.4%/年，在3 mm区域为87.3%（标准差14.5），下降6.7%/年。基线平均BCVA为76.4个字母（标准差11.8；Snellen等效20/30），每年损失1.5个字母。基线MTII与BCVA有显著相关性（1 mm: r = 0.17, P = 0.01; 3 mm: r = 0.14, P = 0.03），而GA面积与BCVA无显著相关性（r = -0.02, P = 0.71）。多变量分析显示，1-mm和3-mm区域的MTII与视力丧失相关（P < 0.0001）。当眼睛按MTII下降率（稳定/中等/快速）分层时，快速组的人在数字上表现出更大的视力下降和GA增长。结论本研究利用MTII表征了GA中枢性黄斑保存的自然历史。结果显示与BCVA在横断面和纵向上有中度但显著的相关性。这些发现表明MTII可能为评估GA的疾病进展提供补充功能背景，需要在临床试验环境中进一步验证。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
{"title":"Longitudinal Study of Macular Preservation and Geographic Atrophy Progression in Age-Related Eye Disease Study 2","authors":"Sairi Zhang MD , Thomas F. Saunders OD , Karl G. Csaky MD , Elvira Agrón MS , Tiarnán D.L. Keenan BM BCh, PhD , Emily Y. Chew MD , Barbara A. Blodi MD , Amitha Domalpally MD, PhD","doi":"10.1016/j.xops.2025.101028","DOIUrl":"10.1016/j.xops.2025.101028","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the natural history of macular tissue preservation in geographic atrophy (GA) by evaluating the relationship between the macular tissue integrity index (MTII) and best-corrected visual acuity (BCVA) over time.</div></div><div><h3>Design</h3><div>Post hoc analysis of Age-Related Eye Disease Study 2 (AREDS2), a multi-center, randomized clinical trial.</div></div><div><h3>Participants</h3><div>Participants from the AREDS2 fundus autofluorescence ancillary study with nonsubfoveal GA.</div></div><div><h3>Methods</h3><div>Areas of GA were segmented by a deep learning algorithm and verified by expert graders. Macular tissue integrity index was defined as the percentage of the macula without GA within the central 1-mm and 3-mm circles. Baseline associations with BCVA were assessed, and longitudinal analyses evaluated GA progression, MTII loss, and BCVA decline over time.</div></div><div><h3>Main Outcome Measures</h3><div>Geographic atrophy area, MTII, and BCVA.</div></div><div><h3>Results</h3><div>Two hundred forty-three eyes (194 participants) were included. The median follow-up was 2 years. At baseline, the mean GA area was 1.8 mm<sup>2</sup> (standard deviation 2.7), and the growth rate was 1.3 mm<sup>2</sup>/year. Baseline mean MTII in the 1-mm zone was 95.2% (standard deviation 9.1) with a decrease of 5.4%/year, and 87.3% (standard deviation 14.5) in the 3-mm zone with a decrease of 6.7%/year. Baseline mean BCVA was 76.4 letters (standard deviation 11.8; Snellen equivalent 20/30) with a 1.5-letter loss/year. Baseline MTII showed significant correlations with BCVA (1 mm: r = 0.17, <em>P</em> = 0.01; 3 mm: r = 0.14, <em>P</em> = 0.03), while GA area was not significantly associated with BCVA (r = –0.02, <em>P</em> = 0.71). Multivariable analysis showed that MTII in the 1-mm and 3-mm zones was associated with visual loss (both <em>P</em> < 0.0001). When eyes were stratified by MTII decline rate (stable/moderate/rapid), those in the rapid group showed numerically greater vision loss and GA growth.</div></div><div><h3>Conclusions</h3><div>This study characterizes the natural history of central macular preservation in GA using MTII. Results show moderate but significant associations with BCVA cross-sectionally and longitudinally. These findings suggest that MTII may offer complementary functional context for evaluating disease progression in GA, warranting further validation in clinical trial settings.</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 2","pages":"Article 101028"},"PeriodicalIF":4.6,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037483","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":"2025-12-02","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 : 2025-11-29DOI: 10.1016/j.xops.2025.101023
Samuel A. Cohen MD , Md Enamul Haque PhD , Suzann Pershing MD, MS , Ann Caroline Fisher MD
<div><h3>Objective</h3><div>To evaluate differences in glaucoma subtype, patient characteristics, and treatment among American Indian or Alaska Native patients compared with other demographic groups.</div></div><div><h3>Design</h3><div>Retrospective observational study.</div></div><div><h3>Participants</h3><div>A total of 1 855 970 patients were diagnosed with glaucoma, 2011 to 2020.</div></div><div><h3>Methods</h3><div>Glaucoma was identified from diagnosis codes. Incidence and associated patient characteristics were determined for primary open-angle glaucoma, juvenile open-angle glaucoma, pigmentary glaucoma, and pseudoexfoliation glaucoma. Treatments (selective laser trabeculoplasty, microinvasive glaucoma surgery [MIGS], and incisional glaucoma surgery) and inferred subspecialty of the treating physician were evaluated for each subtype. Results were stratified by patient race and ethnicity, and multivariable logistic regression was used to evaluate the likelihood of pseudoexfoliation and pigmentary glaucoma, respectively, among American Indian or Alaska Native patients compared with other race/ethnicities.</div></div><div><h3>Main Outcomes Measures</h3><div>Glaucoma incidence by subtype and race and ethnicity; incidence of incisional procedures, MIGS, and selective laser trabeculoplasty in American Indian or Alaska Native patients; and adjusted odds ratios (ORs) for the likelihood of pseudoexfoliation and pigmentary glaucoma based on race/ethnicity.</div></div><div><h3>Results</h3><div>We identified 6270 American Indian or Alaska Native patients with incident glaucoma (0.34%). Compared with other non-White demographic groups, American Indian or Alaska Native patients were >3 times more frequently affected by pseudoexfoliation (4.49% vs. 1.60%) and pigmentary glaucoma (1.37% vs. 0.49%). After adjusting for confounders, American Indian or Alaska Native patients had the highest odds of pseudoexfoliation glaucoma diagnosis (OR, 2.12; 95% confidence interval [CI], 1.85–2.42) compared with other demographic groups, and the second-highest odds of pigmentary glaucoma (OR, 1.33; 95% CI, 1.14–1.56). Pigmentary glaucoma was more often diagnosed at younger ages among American Indian or Alaska Native patients. More American Indian or Alaska Native patients with glaucoma underwent MIGS (15.24%) compared with patients of other races and ethnicities, with more MIGS procedures performed by a glaucoma specialist (33.9%).</div></div><div><h3>Conclusions</h3><div>American Indian or Alaska Native patients have a strikingly increased burden of pigmentary and pseudoexfoliation glaucoma. Because of a smaller population size, these groups are historically less studied and may not be recognized as higher risk. Vigilance is warranted to identify pseudoexfoliation and pigmentary glaucoma among American Indian or Alaska Native patients.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosur
目的评价美国印第安人和阿拉斯加原住民青光眼患者与其他人群相比在青光眼亚型、患者特征和治疗方面的差异。设计回顾性观察性研究。2011年至2020年，共有1855970名患者被诊断为青光眼。方法根据诊断代码对青光眼进行鉴定。确定原发性开角型青光眼、青少年型开角型青光眼、色素性青光眼和假剥脱性青光眼的发病率和相关患者特征。对每种亚型的治疗方法（选择性激光小梁成形术、微创青光眼手术和切口青光眼手术）和治疗医师推断的亚专科进行评估。结果按患者种族和民族分层，并使用多变量logistic回归分别评估与其他种族/民族相比，美国印第安人或阿拉斯加原住民患者的假角质脱落和色素性青光眼的可能性。青光眼发病率按亚型、人种和民族划分；切口手术、MIGS和选择性激光小梁成形术在美国印第安人或阿拉斯加原住民患者中的发生率；并根据种族/民族调整了假脱落和色素性青光眼可能性的比值比（ORs）。结果6270例美国印第安人或阿拉斯加原住民患者发生青光眼（0.34%）。与其他非白人人群相比，美国印第安人或阿拉斯加原住民患者发生假角质脱落（4.49% vs. 1.60%）和色素性青光眼（1.37% vs. 0.49%）的频率是其他非白人人群的3倍。在调整混杂因素后，与其他人群相比，美洲印第安人或阿拉斯加原住民患者的假脱落性青光眼诊断几率最高（or, 2.12； 95%可信区间[CI]， 1.85-2.42），色素青光眼的诊断几率第二高（or, 1.33; 95% CI, 1.14-1.56）。色素性青光眼在美国印第安人和阿拉斯加原住民患者中更常在年轻时被诊断出来。与其他种族和民族的患者相比，更多的美国印第安人或阿拉斯加原住民青光眼患者接受了MIGS(15.24%)，青光眼专家进行了更多的MIGS手术（33.9%）。结论美洲印第安人和阿拉斯加原住民患者的色素性和假脱落性青光眼负担明显增加。由于人口规模较小，历史上对这些群体的研究较少，可能不会被认为是高风险群体。在美洲印第安人或阿拉斯加土著患者中，应警惕识别假性脱落和色素性青光眼。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
{"title":"Burden of Pseudoexfoliation and Pigmentary Glaucoma among American Indian or Alaska Native Patients","authors":"Samuel A. Cohen MD , Md Enamul Haque PhD , Suzann Pershing MD, MS , Ann Caroline Fisher MD","doi":"10.1016/j.xops.2025.101023","DOIUrl":"10.1016/j.xops.2025.101023","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate differences in glaucoma subtype, patient characteristics, and treatment among American Indian or Alaska Native patients compared with other demographic groups.</div></div><div><h3>Design</h3><div>Retrospective observational study.</div></div><div><h3>Participants</h3><div>A total of 1 855 970 patients were diagnosed with glaucoma, 2011 to 2020.</div></div><div><h3>Methods</h3><div>Glaucoma was identified from diagnosis codes. Incidence and associated patient characteristics were determined for primary open-angle glaucoma, juvenile open-angle glaucoma, pigmentary glaucoma, and pseudoexfoliation glaucoma. Treatments (selective laser trabeculoplasty, microinvasive glaucoma surgery [MIGS], and incisional glaucoma surgery) and inferred subspecialty of the treating physician were evaluated for each subtype. Results were stratified by patient race and ethnicity, and multivariable logistic regression was used to evaluate the likelihood of pseudoexfoliation and pigmentary glaucoma, respectively, among American Indian or Alaska Native patients compared with other race/ethnicities.</div></div><div><h3>Main Outcomes Measures</h3><div>Glaucoma incidence by subtype and race and ethnicity; incidence of incisional procedures, MIGS, and selective laser trabeculoplasty in American Indian or Alaska Native patients; and adjusted odds ratios (ORs) for the likelihood of pseudoexfoliation and pigmentary glaucoma based on race/ethnicity.</div></div><div><h3>Results</h3><div>We identified 6270 American Indian or Alaska Native patients with incident glaucoma (0.34%). Compared with other non-White demographic groups, American Indian or Alaska Native patients were >3 times more frequently affected by pseudoexfoliation (4.49% vs. 1.60%) and pigmentary glaucoma (1.37% vs. 0.49%). After adjusting for confounders, American Indian or Alaska Native patients had the highest odds of pseudoexfoliation glaucoma diagnosis (OR, 2.12; 95% confidence interval [CI], 1.85–2.42) compared with other demographic groups, and the second-highest odds of pigmentary glaucoma (OR, 1.33; 95% CI, 1.14–1.56). Pigmentary glaucoma was more often diagnosed at younger ages among American Indian or Alaska Native patients. More American Indian or Alaska Native patients with glaucoma underwent MIGS (15.24%) compared with patients of other races and ethnicities, with more MIGS procedures performed by a glaucoma specialist (33.9%).</div></div><div><h3>Conclusions</h3><div>American Indian or Alaska Native patients have a strikingly increased burden of pigmentary and pseudoexfoliation glaucoma. Because of a smaller population size, these groups are historically less studied and may not be recognized as higher risk. Vigilance is warranted to identify pseudoexfoliation and pigmentary glaucoma among American Indian or Alaska Native patients.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosur","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101023"},"PeriodicalIF":4.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925896","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号