Pub Date : 2025-11-20DOI: 10.1016/j.xops.2025.101015
Xiang-Hua Tang PhD, MD, Zhi-Peng Lai PhD, MD, Sheng-Song Xu PhD, MD, Jin-Yi Xu PhD, MD, Xiao Wang MD, Xing-Yu Lei BMed, Zhou-Yue Li PhD, MD, Xiao Yang PhD, MD
Objective
The underlying mechanism of refractive development—whether it is confined to the local eyeball or involves the central visual pathways—remains controversial. This study aimed to explore the effect of optic nerve crush (ONC) on refractive development and lens-induced myopia (LIM) in mice and its potential mechanism.
Design
Laboratory experimental study.
Subjects
Three-week-old C57BL/6 mice were used in this study. The animals were divided into the following experimental groups: ONC group versus sham surgery (SHAM) group; ONC combined with LIM (ONC-LIM) group versus SHAM combined with LIM (SHAM-LIM) group; LIM followed by ONC group verus LIM group versus plano lens group.
Methods
The refraction and ocular biological parameters were measured. Bulk RNA-sequencing analysis was performed on retinas from the ONC group and the SHAM group. Differential expression analysis between groups was conducted using edgeR. Differentially expressed genes were selected by trend analysis to investigate the expression trends over different refractive conditions after ONC. The Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction analysis, and gene set enrichment analysis were conducted, and quantitative reverse transcription polymerase chain reaction was applied for validation.
Main Outcome Measures
The axial length (AL).
Results
The results indicated that, after ONC, 50% of the mice showed a myopic shift and 25% showed a hyperopic shift, and the changes in AL were consistent with refraction. The ONC-LIM group failed to develop myopic shift or axial elongation, unlike the SHAM-LIM group, suggesting that optical defocus could not induce a myopic shift in mice after ONC. RNA-sequencing analysis revealed several pathways associated with post-ONC refractive status, including glutamatergic synapse, gonadotropin-releasing hormone signaling, and long-term depression.
Conclusions
Our findings suggest that intact optic nerve is necessary for normal murine emmetropization and for the development of LIM. While local ocular mechanisms remain the established paradigm for refractive regulation, our experimental results indicate the potential involvement of CNS pathways in ocular growth regulation. Further studies are needed to elucidate the precise mechanisms and potential interplay between local and central regulatory systems.
Financial Disclosure(s)
The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"The Effect of Optic Nerve Crush on Lens-Induced Myopia in Mice","authors":"Xiang-Hua Tang PhD, MD, Zhi-Peng Lai PhD, MD, Sheng-Song Xu PhD, MD, Jin-Yi Xu PhD, MD, Xiao Wang MD, Xing-Yu Lei BMed, Zhou-Yue Li PhD, MD, Xiao Yang PhD, MD","doi":"10.1016/j.xops.2025.101015","DOIUrl":"10.1016/j.xops.2025.101015","url":null,"abstract":"<div><h3>Objective</h3><div>The underlying mechanism of refractive development—whether it is confined to the local eyeball or involves the central visual pathways—remains controversial. This study aimed to explore the effect of optic nerve crush (ONC) on refractive development and lens-induced myopia (LIM) in mice and its potential mechanism.</div></div><div><h3>Design</h3><div>Laboratory experimental study.</div></div><div><h3>Subjects</h3><div>Three-week-old C57BL/6 mice were used in this study. The animals were divided into the following experimental groups: ONC group versus sham surgery (SHAM) group; ONC combined with LIM (ONC-LIM) group versus SHAM combined with LIM (SHAM-LIM) group; LIM followed by ONC group verus LIM group versus plano lens group.</div></div><div><h3>Methods</h3><div>The refraction and ocular biological parameters were measured. Bulk RNA-sequencing analysis was performed on retinas from the ONC group and the SHAM group. Differential expression analysis between groups was conducted using edgeR. Differentially expressed genes were selected by trend analysis to investigate the expression trends over different refractive conditions after ONC. The Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction analysis, and gene set enrichment analysis were conducted, and quantitative reverse transcription polymerase chain reaction was applied for validation.</div></div><div><h3>Main Outcome Measures</h3><div>The axial length (AL).</div></div><div><h3>Results</h3><div>The results indicated that, after ONC, 50% of the mice showed a myopic shift and 25% showed a hyperopic shift, and the changes in AL were consistent with refraction. The ONC-LIM group failed to develop myopic shift or axial elongation, unlike the SHAM-LIM group, suggesting that optical defocus could not induce a myopic shift in mice after ONC. RNA-sequencing analysis revealed several pathways associated with post-ONC refractive status, including glutamatergic synapse, gonadotropin-releasing hormone signaling, and long-term depression.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that intact optic nerve is necessary for normal murine emmetropization and for the development of LIM. While local ocular mechanisms remain the established paradigm for refractive regulation, our experimental results indicate the potential involvement of CNS pathways in ocular growth regulation. Further studies are needed to elucidate the precise mechanisms and potential interplay between local and central regulatory systems.</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 101015"},"PeriodicalIF":4.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884486","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 : 2025-11-17DOI: 10.1016/j.xops.2025.101013
Lixue Liu MD, PhD , Mingyuan Li MS , Yuxuan Wu MD, PhD , Zizheng Cao MD , Yuanjun Shang MD , Lanqin Zhao MS , Zhenyu Wang MD , Junwei Tan BM , Yan Yuan BM , Wenbin Huang MD, PhD , Jinghui Wang PhD , Jianqiao Li PhD , Fabao Xu PhD , Zhangkai Lian MD , Jianyu Pang MS , Fan Xu PhD , Ningning Tang PhD , Xingru He DrPH, MBA , Yan Xu MD , Kun Zeng MD, PhD , Haotian Lin MD, PhD
<div><h3>Purpose</h3><div>To develop and validate OCT-PRO, a multimodal machine learning model integrating OCT images and clinical traits to predict postoperative visual outcomes in cataract patients.</div></div><div><h3>Design</h3><div>Multicenter prospective cohort study.</div></div><div><h3>Participants</h3><div>A total of 2225 eyes from 1911 cataract patients were enrolled, including 1304 participants from Zhongshan Ophthalmic Center for model development and 607 from 6 hospitals across China for external testing.</div></div><div><h3>Methods</h3><div>All participants underwent standardized preoperative examinations including macular OCT and clinical data collection, followed by phacoemulsification and intraocular lens implantation. Postoperative best-corrected visual acuity (BCVA) was assessed at 4 weeks after surgery. A multimodal model was constructed using deep learning techniques, combining image features extracted via InceptionResNetV2 and structured metadata processed by fully connected layers. Model performance was assessed using mean absolute error (MAE) and root mean square error (RMSE) and compared with traditional laser interferometry and ophthalmologist predictions. Subgroup analysis and explainability assessments were conducted to evaluate generalizability and model attention.</div></div><div><h3>Main Outcome Measures</h3><div>Prediction error of postoperative BCVA (logarithm of the minimum angle of resolution [logMAR]) measured by MAE and RMSE.</div></div><div><h3>Results</h3><div>In the internal test data set, OCT-PRO achieved improved performance, with lower MAE and RMSE (0.128 and 0.211 logMAR) compared with the OCT-only model (0.138 and 0.226 logMAR), metadata-only model (0.161 and 0.234 logMAR) and laser interferometry (0.381 and 0.554 logMAR). In the external test data set, OCT-PRO achieved an MAE of 0.168 logMAR, significantly outperforming the OCT-only (0.183 logMAR, <em>P</em> = 0.003) and metadata-only models (0.229 logMAR, <em>P</em> < 0.001). Subgroup analyses confirmed consistent advantages of OCT-PRO across different cataract subtypes and baseline preoperative BCVA groups. Model interpretability analysis highlighted the importance of preoperative BCVA, age, and macular foveal structure, with greater reliance on OCT features than clinical metadata—especially in complex or low preoperative BCVA cases. In a head-to-head comparison, the model consistently outperformed both junior and senior ophthalmologists in predictive accuracy across various clinical subtypes.</div></div><div><h3>Conclusions</h3><div>OCT-PRO enables accurate prediction of postoperative visual outcomes in cataract surgery, outperforming conventional methods and ophthalmologists. It holds promise as a valuable decision-support tool to assist surgical decision-making and improve health care resource allocation.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author has no/the authors have no proprietary or commercial interest in any materia
目的开发并验证OCT- pro多模态机器学习模型,将OCT图像与临床特征相结合,用于预测白内障患者术后视力结果。设计多中心前瞻性队列研究。共纳入1911例白内障患者的2225只眼,其中1304只来自中山眼科中心进行模型开发,607只来自全国6家医院进行外部测试。方法术前进行黄斑OCT检查及临床资料收集,行超声乳化术及人工晶状体植入术。术后4周评估最佳矫正视力(BCVA)。结合InceptionResNetV2提取的图像特征和全连接层处理的结构化元数据,利用深度学习技术构建了多模态模型。使用平均绝对误差(MAE)和均方根误差(RMSE)评估模型的性能,并与传统激光干涉测量和眼科医生的预测进行比较。通过亚组分析和可解释性评估来评估通用性和模型关注。主要观察指标用MAE和RMSE测量术后BCVA的预测误差(最小分辨角的对数[logMAR])。结果在内部测试数据集中,OCT-PRO比oct -纯模型(0.138和0.226 logMAR)、元数据模型(0.161和0.234 logMAR)和激光干涉测量(0.381和0.554 logMAR)具有更低的MAE和RMSE(0.128和0.211 logMAR)。在外部测试数据集中,OCT-PRO获得了0.168 logMAR的MAE,显著优于OCT-only模型(0.183 logMAR, P = 0.003)和元数据模型(0.229 logMAR, P < 0.001)。亚组分析证实OCT-PRO在不同白内障亚型和基线术前BCVA组中具有一致的优势。模型可解释性分析强调了术前BCVA、年龄和黄斑中央凹结构的重要性,与临床元数据相比,对OCT特征的依赖性更大,尤其是在复杂或术前BCVA较低的病例中。在头对头比较中,该模型在各种临床亚型的预测准确性方面始终优于初级和高级眼科医生。结论soct - pro能准确预测白内障术后视力,优于常规方法和眼科医生。它有望成为一种有价值的决策支持工具,以协助外科决策和改善卫生保健资源分配。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":"OCT-PRO: A Multimodal Model Integrating OCT and Clinical Traits to Predict Postoperative Outcomes in Cataract Patients","authors":"Lixue Liu MD, PhD , Mingyuan Li MS , Yuxuan Wu MD, PhD , Zizheng Cao MD , Yuanjun Shang MD , Lanqin Zhao MS , Zhenyu Wang MD , Junwei Tan BM , Yan Yuan BM , Wenbin Huang MD, PhD , Jinghui Wang PhD , Jianqiao Li PhD , Fabao Xu PhD , Zhangkai Lian MD , Jianyu Pang MS , Fan Xu PhD , Ningning Tang PhD , Xingru He DrPH, MBA , Yan Xu MD , Kun Zeng MD, PhD , Haotian Lin MD, PhD","doi":"10.1016/j.xops.2025.101013","DOIUrl":"10.1016/j.xops.2025.101013","url":null,"abstract":"<div><h3>Purpose</h3><div>To develop and validate OCT-PRO, a multimodal machine learning model integrating OCT images and clinical traits to predict postoperative visual outcomes in cataract patients.</div></div><div><h3>Design</h3><div>Multicenter prospective cohort study.</div></div><div><h3>Participants</h3><div>A total of 2225 eyes from 1911 cataract patients were enrolled, including 1304 participants from Zhongshan Ophthalmic Center for model development and 607 from 6 hospitals across China for external testing.</div></div><div><h3>Methods</h3><div>All participants underwent standardized preoperative examinations including macular OCT and clinical data collection, followed by phacoemulsification and intraocular lens implantation. Postoperative best-corrected visual acuity (BCVA) was assessed at 4 weeks after surgery. A multimodal model was constructed using deep learning techniques, combining image features extracted via InceptionResNetV2 and structured metadata processed by fully connected layers. Model performance was assessed using mean absolute error (MAE) and root mean square error (RMSE) and compared with traditional laser interferometry and ophthalmologist predictions. Subgroup analysis and explainability assessments were conducted to evaluate generalizability and model attention.</div></div><div><h3>Main Outcome Measures</h3><div>Prediction error of postoperative BCVA (logarithm of the minimum angle of resolution [logMAR]) measured by MAE and RMSE.</div></div><div><h3>Results</h3><div>In the internal test data set, OCT-PRO achieved improved performance, with lower MAE and RMSE (0.128 and 0.211 logMAR) compared with the OCT-only model (0.138 and 0.226 logMAR), metadata-only model (0.161 and 0.234 logMAR) and laser interferometry (0.381 and 0.554 logMAR). In the external test data set, OCT-PRO achieved an MAE of 0.168 logMAR, significantly outperforming the OCT-only (0.183 logMAR, <em>P</em> = 0.003) and metadata-only models (0.229 logMAR, <em>P</em> < 0.001). Subgroup analyses confirmed consistent advantages of OCT-PRO across different cataract subtypes and baseline preoperative BCVA groups. Model interpretability analysis highlighted the importance of preoperative BCVA, age, and macular foveal structure, with greater reliance on OCT features than clinical metadata—especially in complex or low preoperative BCVA cases. In a head-to-head comparison, the model consistently outperformed both junior and senior ophthalmologists in predictive accuracy across various clinical subtypes.</div></div><div><h3>Conclusions</h3><div>OCT-PRO enables accurate prediction of postoperative visual outcomes in cataract surgery, outperforming conventional methods and ophthalmologists. It holds promise as a valuable decision-support tool to assist surgical decision-making and improve health care resource allocation.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author has no/the authors have no proprietary or commercial interest in any materia","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101013"},"PeriodicalIF":4.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798002","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 : 2025-11-17DOI: 10.1016/j.xops.2025.101011
Taiga Inooka MD, PhD , Yuki Kimura MD , Shota Fujikawa , Sayuri Yasuda MD, PhD , Taro Kominami MD, PhD , Tetsuhito Kojima MD, PhD , Shinji Ueno MD, PhD , Yasuki Ito MD, PhD , Koji M. Nishiguchi MD, PhD , Kenya Yuki MD, PhD
Purpose
Adult axial length (AL) elongation in adults is associated with pathologic outcomes; however, population-based longitudinal evidence remains limited, and pragmatic risk profiling is unclear. We aimed to quantify the prevalence and annual rate of AL elongation in adults and identify independent determinants in a population-based health-check cohort.
Design
Retrospective, single-center cohort study.
Subjects
A total of 4016 adults aged 22.4 to 93.0 years (8032 eyes; 21 421 visits) undergoing a Japanese health-check program, with a median follow-up of 5.31 years.
Methods
For each eye, the annual AL change (mm/year) was estimated as the within-eye linear-regression slope and classified as severe (≥0.10), moderate (≥0.05 to <0.10), mild (≥0.00 to <0.05), or nil (<0). Associations were evaluated using a class-weighted proportional-odds ordinal logistic model. Pair-level change-point analysis modeled which eye elongated faster.
Main Outcome Measures
Proportion of eyes by annual AL elongation severity, adjusted odds ratios (ORs) for determinants of more-severe elongation, and the baseline-AL intersection at which the longer eye becomes more likely to elongate faster.
Results
Nil and mild accounted for 98.6% of eyes; moderate and severe were uncommon (1.3% and 0.2%). Independent determinants of greater severity included longer baseline AL (OR, 1.34 per 1 mm), larger interocular difference in AL (OR, 7.18 per 1 mm), myopic maculopathy including tessellated fundus (OR, 2.79), and female sex (OR, 3.05). Change-point analysis identified an intersection near 28.56 mm in the longer eye: below this value, the estimated probability that it would elongate faster was approximately 0.50 (no consistent lateral preference), whereas above it the probability exceeded 0.50 with wide uncertainty at high baseline AL values.
Conclusions
Adult AL elongation is uncommon and slow; risk is concentrated in eyes with longer AL, greater axial asymmetry, myopic maculopathy, and in female adults. These readily measured features can inform follow-up decisions in health-check settings; pair-level estimates around 28.6 mm may help prioritize eyes for follow-up but should be interpreted cautiously.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Risk Factors for Adult Axial Length Elongation: A 5-Year Population-Based Cohort Study","authors":"Taiga Inooka MD, PhD , Yuki Kimura MD , Shota Fujikawa , Sayuri Yasuda MD, PhD , Taro Kominami MD, PhD , Tetsuhito Kojima MD, PhD , Shinji Ueno MD, PhD , Yasuki Ito MD, PhD , Koji M. Nishiguchi MD, PhD , Kenya Yuki MD, PhD","doi":"10.1016/j.xops.2025.101011","DOIUrl":"10.1016/j.xops.2025.101011","url":null,"abstract":"<div><h3>Purpose</h3><div>Adult axial length (AL) elongation in adults is associated with pathologic outcomes; however, population-based longitudinal evidence remains limited, and pragmatic risk profiling is unclear. We aimed to quantify the prevalence and annual rate of AL elongation in adults and identify independent determinants in a population-based health-check cohort.</div></div><div><h3>Design</h3><div>Retrospective, single-center cohort study.</div></div><div><h3>Subjects</h3><div>A total of 4016 adults aged 22.4 to 93.0 years (8032 eyes; 21 421 visits) undergoing a Japanese health-check program, with a median follow-up of 5.31 years.</div></div><div><h3>Methods</h3><div>For each eye, the annual AL change (mm/year) was estimated as the within-eye linear-regression slope and classified as severe (≥0.10), moderate (≥0.05 to <0.10), mild (≥0.00 to <0.05), or nil (<0). Associations were evaluated using a class-weighted proportional-odds ordinal logistic model. Pair-level change-point analysis modeled which eye elongated faster.</div></div><div><h3>Main Outcome Measures</h3><div>Proportion of eyes by annual AL elongation severity, adjusted odds ratios (ORs) for determinants of more-severe elongation, and the baseline-AL intersection at which the longer eye becomes more likely to elongate faster.</div></div><div><h3>Results</h3><div>Nil and mild accounted for 98.6% of eyes; moderate and severe were uncommon (1.3% and 0.2%). Independent determinants of greater severity included longer baseline AL (OR, 1.34 per 1 mm), larger interocular difference in AL (OR, 7.18 per 1 mm), myopic maculopathy including tessellated fundus (OR, 2.79), and female sex (OR, 3.05). Change-point analysis identified an intersection near 28.56 mm in the longer eye: below this value, the estimated probability that it would elongate faster was approximately 0.50 (no consistent lateral preference), whereas above it the probability exceeded 0.50 with wide uncertainty at high baseline AL values.</div></div><div><h3>Conclusions</h3><div>Adult AL elongation is uncommon and slow; risk is concentrated in eyes with longer AL, greater axial asymmetry, myopic maculopathy, and in female adults. These readily measured features can inform follow-up decisions in health-check settings; pair-level estimates around 28.6 mm may help prioritize eyes for follow-up but should be interpreted cautiously.</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 101011"},"PeriodicalIF":4.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798068","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 : 2025-11-14DOI: 10.1016/j.xops.2025.101009
Lawrence J. Singerman MD , Jean-Pierre Hubschman MD , Martin Friedlander MD, PhD , Emily Y. Chew MD , Catherine Egan PhD , Muna Bitar PharmD , Thomas M. Aaberg Jr. MD
Objective
To primarily assess long-term safety and retinal imaging outcomes of NT-501 (revakinagene taroretcel-lwey), which releases ciliary neurotrophic factor into the vitreous over an extended time, for treating macular telangiectasia type 2 (MacTel).
Design
Phase I, nonrandomized, multicenter, open-label extension study.
Participants
Six participants with bilateral MacTel who completed the parent 60-month phase I study.
Methods
In the parent study, participants had NT-501 surgically implanted in the study eye. The eye with more advanced disease was determined to be the study eye. For the purposes of this extension study, the fellow eye provided untreated natural history data. The extension study included visits 72, 84, 96, and 108 months postimplantation.
Main Outcome Measures
Safety outcomes included adverse events (AEs), change from baseline in best-corrected visual acuity (BCVA), and the proportions of eyes with ≥10- or ≥15-letter loss in BCVA from baseline. Retinal imaging variables included change from baseline in ellipsoid zone (EZ) (inner segment/outer segment) area loss and proportion of study eyes with ≥35% increase from baseline in EZ area loss.
Results
All implants were retained through the final study visit. All ocular treatment-emergent AEs were mild to moderate; none resulted in study discontinuation. No study eyes had ≥15-letter loss in BCVA from baseline at any study visit. Similarly, no study eyes had ≥10-letter loss at months 72, 84, and 96; 1 study eye (17%) experienced it at month 108. The portion of study eyes with a ≥35% increase in EZ area loss from baseline was lower (range, 50%–60%) relative to fellow eyes (range, 75%–100%).
Conclusions
Over the 9-year follow-up period, NT-501 was well tolerated and safe. Further studies are ongoing to investigate the long-term efficacy of NT-501 for treating MacTel.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Results from a Phase I Extension Study of Ciliary Neurotrophic Factor in Patients with Macular Telangiectasia Type 2","authors":"Lawrence J. Singerman MD , Jean-Pierre Hubschman MD , Martin Friedlander MD, PhD , Emily Y. Chew MD , Catherine Egan PhD , Muna Bitar PharmD , Thomas M. Aaberg Jr. MD","doi":"10.1016/j.xops.2025.101009","DOIUrl":"10.1016/j.xops.2025.101009","url":null,"abstract":"<div><h3>Objective</h3><div>To primarily assess long-term safety and retinal imaging outcomes of NT-501 (revakinagene taroretcel-lwey), which releases ciliary neurotrophic factor into the vitreous over an extended time, for treating macular telangiectasia type 2 (MacTel).</div></div><div><h3>Design</h3><div>Phase I, nonrandomized, multicenter, open-label extension study.</div></div><div><h3>Participants</h3><div>Six participants with bilateral MacTel who completed the parent 60-month phase I study.</div></div><div><h3>Methods</h3><div>In the parent study, participants had NT-501 surgically implanted in the study eye. The eye with more advanced disease was determined to be the study eye. For the purposes of this extension study, the fellow eye provided untreated natural history data. The extension study included visits 72, 84, 96, and 108 months postimplantation.</div></div><div><h3>Main Outcome Measures</h3><div>Safety outcomes included adverse events (AEs), change from baseline in best-corrected visual acuity (BCVA), and the proportions of eyes with ≥10- or ≥15-letter loss in BCVA from baseline. Retinal imaging variables included change from baseline in ellipsoid zone (EZ) (inner segment/outer segment) area loss and proportion of study eyes with ≥35% increase from baseline in EZ area loss.</div></div><div><h3>Results</h3><div>All implants were retained through the final study visit. All ocular treatment-emergent AEs were mild to moderate; none resulted in study discontinuation. No study eyes had ≥15-letter loss in BCVA from baseline at any study visit. Similarly, no study eyes had ≥10-letter loss at months 72, 84, and 96; 1 study eye (17%) experienced it at month 108. The portion of study eyes with a ≥35% increase in EZ area loss from baseline was lower (range, 50%–60%) relative to fellow eyes (range, 75%–100%).</div></div><div><h3>Conclusions</h3><div>Over the 9-year follow-up period, NT-501 was well tolerated and safe. Further studies are ongoing to investigate the long-term efficacy of NT-501 for treating MacTel.</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 101009"},"PeriodicalIF":4.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798001","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 : 2025-11-12DOI: 10.1016/j.xops.2025.100999
Jost B. Jonas MD , Rahul A. Jonas MD , Mukharram M. Bikbov MD, PhD , Gyulli M. Kazakbaeva MD , Ellina M. Iakupova MD , Ya Xing Wang MD , Vinay Nangia MD , Songhomitra Panda-Jonas MD
Objective
To determine the cutoff value in axial length between moderate myopia versus high myopia in dependence on the prevalence of myopic macular degeneration (MMD).
Design
Population-based studies conducted in Russia, China, and India.
Participants
The project included the population-based investigations of the Beijing Eye Study (n = 3325; age: 40+ years), Russian Ural Eye and Medical Study (n = 5586 participants; age: 40+ years), Ural Very Old Study (n = 541; age: 85+ years) and Ural Children Eye Study (n = 4255; age: 6+ years), and Central India Eye and Medical Study (n = 4467; age: 30+ years).
Methods
The participants underwent a series of general medical and ophthalmic examinations, including fundus photography and ocular biometry. Myopic macular degeneration was defined according to the Meta-analysis for Pathologic Myopia Study Group.
Main Outcome Measures
Prevalence of MMD in dependence on axial length.
Results
The total study population included 36 123 eyes (18 471 individuals) (age: 47.4 ± 23.4 years; range: 6–100 years) (axial length: 23.2 ± 1.1 mm; range: 18.22–34.20 mm). In the total study population, higher MMD stage was associated with longer axial length (β: 0.55; B: 0.14; 95% confidence interval [CI]: 0.14–0.15; P < 0.001), older age (β: 0.09; B: 0.001; 95% CI: 0.001–0.001; P < 0.001), female sex (β: 0.12; B: 0.07; 95% CI: 0.06–0.07; P < 0.001), and Indian ethnicity (β: 0.10; B: 0.07; 95% CI: 0.06–0.07; P < 0.001). Higher prevalence of MMD stage 2+ and 3+ correlated with longer axial length (odds ratio [OR]: 9.10; 95% CI: 6.93–11.9; P < 0.001 and OR: 6.90; 95% CI: 5.14–9.26; P < 0.001, respectively), older age (OR: 1.06; 95% CI: 1.04–1.08; P < 0.001 and OR: 1.08; 95% CI: 1.05–1.11; P < 0.001, respectively), and Indian ethnicity (OR: 6.96; 95% CI: 2.70–17.9; P < 0.001 and OR: 3.69; 95% CI: 1.26–10.8; P = 0.02, respectively). The turning points of the regression curves of the associations of axial length with prevalence of MMD stage 2+ and 3+ were located at axial length values of between 26.0 and 26.5 mm, respectively.
Conclusions
The axial length-related cutoff for moderate versus high myopia was located approximately at 26.0 and 26.5 mm for the prevalence of MMD stage 2+ and 3+, respectively, with higher values for younger individuals. Myopic macular degeneration prevalence was higher in the Indian cohort.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Differentiation Between Moderate Versus High Myopia: The 2-Continent Eye Study","authors":"Jost B. Jonas MD , Rahul A. Jonas MD , Mukharram M. Bikbov MD, PhD , Gyulli M. Kazakbaeva MD , Ellina M. Iakupova MD , Ya Xing Wang MD , Vinay Nangia MD , Songhomitra Panda-Jonas MD","doi":"10.1016/j.xops.2025.100999","DOIUrl":"10.1016/j.xops.2025.100999","url":null,"abstract":"<div><h3>Objective</h3><div>To determine the cutoff value in axial length between moderate myopia versus high myopia in dependence on the prevalence of myopic macular degeneration (MMD).</div></div><div><h3>Design</h3><div>Population-based studies conducted in Russia, China, and India.</div></div><div><h3>Participants</h3><div>The project included the population-based investigations of the Beijing Eye Study (n = 3325; age: 40+ years), Russian Ural Eye and Medical Study (n = 5586 participants; age: 40+ years), Ural Very Old Study (n = 541; age: 85+ years) and Ural Children Eye Study (n = 4255; age: 6+ years), and Central India Eye and Medical Study (n = 4467; age: 30+ years).</div></div><div><h3>Methods</h3><div>The participants underwent a series of general medical and ophthalmic examinations, including fundus photography and ocular biometry. Myopic macular degeneration was defined according to the Meta-analysis for Pathologic Myopia Study Group.</div></div><div><h3>Main Outcome Measures</h3><div>Prevalence of MMD in dependence on axial length.</div></div><div><h3>Results</h3><div>The total study population included 36 123 eyes (18 471 individuals) (age: 47.4 ± 23.4 years; range: 6–100 years) (axial length: 23.2 ± 1.1 mm; range: 18.22–34.20 mm). In the total study population, higher MMD stage was associated with longer axial length (β: 0.55; B: 0.14; 95% confidence interval [CI]: 0.14–0.15; <em>P</em> < 0.001), older age (β: 0.09; B: 0.001; 95% CI: 0.001–0.001; <em>P</em> < 0.001), female sex (β: 0.12; B: 0.07; 95% CI: 0.06–0.07; <em>P</em> < 0.001), and Indian ethnicity (β: 0.10; B: 0.07; 95% CI: 0.06–0.07; <em>P</em> < 0.001). Higher prevalence of MMD stage 2+ and 3+ correlated with longer axial length (odds ratio [OR]: 9.10; 95% CI: 6.93–11.9; <em>P</em> < 0.001 and OR: 6.90; 95% CI: 5.14–9.26; <em>P</em> < 0.001, respectively), older age (OR: 1.06; 95% CI: 1.04–1.08; <em>P</em> < 0.001 and OR: 1.08; 95% CI: 1.05–1.11; <em>P</em> < 0.001, respectively), and Indian ethnicity (OR: 6.96; 95% CI: 2.70–17.9; <em>P</em> < 0.001 and OR: 3.69; 95% CI: 1.26–10.8; <em>P</em> = 0.02, respectively). The turning points of the regression curves of the associations of axial length with prevalence of MMD stage 2+ and 3+ were located at axial length values of between 26.0 and 26.5 mm, respectively.</div></div><div><h3>Conclusions</h3><div>The axial length-related cutoff for moderate versus high myopia was located approximately at 26.0 and 26.5 mm for the prevalence of MMD stage 2+ and 3+, respectively, with higher values for younger individuals. Myopic macular degeneration prevalence was higher in the Indian cohort.</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 100999"},"PeriodicalIF":4.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798069","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 : 2025-11-12DOI: 10.1016/j.xops.2025.101008
Kyle Bolo MD , Tran Huy Nguyen MS , Sreenidhi Iyengar MS , Zhiwei Li MS , Van Nguyen MD , Brandon J. Wong MD , Jiun L. Do MD, PhD , Jose-Luis Ambite PhD , Carl Kesselman PhD , Lauren P. Daskivich MD , Benjamin Y. Xu MD, PhD
Purpose
To compare the performance of a vision transformer-based foundation model (RETFound) and a supervised convolutional neural network (VGG-19) for detecting referable glaucoma from fundus photographs.
Design
An evaluation of diagnostic technology.
Participants
Six thousand one hundred sixteen participants from the Los Angeles County Department of Health Services Teleretinal Screening Program.
Methods
Fundus photographs were labeled for referable glaucoma (cup-to-disc ratio ≥0.6) by certified optometrists. Four deep learning models were trained on cropped and uncropped images (training N = 8996; validation N = 3002) using 2 architectures: RETFound, a vision transformer with self-supervised pretraining on fundus photographs, and VGG-19. Models were evaluated on a held-out test set (N = 1000) labeled by glaucoma specialists and an external test set (N = 300) from University of Southern California clinics. Performance was assessed while varying training set size and stratifying by demographic factors. xRAI was used for saliency mapping.
Main Outcome Measures
Area under the receiver operating characteristic curve (AUC–ROC) and threshold-specific metrics.
Results
The cropped image VGG-19 model achieved the highest AUC–ROC (0.924 [0.907–0.940]), which was comparable (P = 0.07) to the cropped image RETFound model (0.911 [0.892–0.930]), which achieved the highest Youden-optimal performance (sensitivity 82.6% and specificity 88.2%) and F1 score (0.801). Cropped image models outperformed their uncropped counterparts (RETFound 0.889 [0.868–0.909], VGG-19 0.898 [0.879–0.917]) within each architecture (P < 0.001 for AUC–ROC comparisons). The uncropped image RETFound model performed best on external data (0.886 [0.849–0.924] vs. the next-highest 0.797 [0.746–0.848], P < 0.001 for AUC–ROC comparisons). RETFound models had a performance advantage when trained on smaller datasets (N < 2000 images), and the cropped image RETFound model performed consistently across ethnic groups (P = 0.20), whereas the others did not (P < 0.04). Performance did not vary by age or gender. Saliency maps for both architectures consistently included the optic nerve.
Conclusions
Although both RETFound and VGG-19 models performed well for classification of referable glaucoma, foundation models may be preferable when training data are limited and when domain shift is expected. Training models using images cropped to the region of the optic nerve improves performance regardless of architecture but may reduce model generalizability.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Comparison of RETFound and a Supervised Convolutional Neural Network for Detection of Referable Glaucoma from Fundus Photographs","authors":"Kyle Bolo MD , Tran Huy Nguyen MS , Sreenidhi Iyengar MS , Zhiwei Li MS , Van Nguyen MD , Brandon J. Wong MD , Jiun L. Do MD, PhD , Jose-Luis Ambite PhD , Carl Kesselman PhD , Lauren P. Daskivich MD , Benjamin Y. Xu MD, PhD","doi":"10.1016/j.xops.2025.101008","DOIUrl":"10.1016/j.xops.2025.101008","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the performance of a vision transformer-based foundation model (RETFound) and a supervised convolutional neural network (VGG-19) for detecting referable glaucoma from fundus photographs.</div></div><div><h3>Design</h3><div>An evaluation of diagnostic technology.</div></div><div><h3>Participants</h3><div>Six thousand one hundred sixteen participants from the Los Angeles County Department of Health Services Teleretinal Screening Program.</div></div><div><h3>Methods</h3><div>Fundus photographs were labeled for referable glaucoma (cup-to-disc ratio ≥0.6) by certified optometrists. Four deep learning models were trained on cropped and uncropped images (training N = 8996; validation N = 3002) using 2 architectures: RETFound, a vision transformer with self-supervised pretraining on fundus photographs, and VGG-19. Models were evaluated on a held-out test set (N = 1000) labeled by glaucoma specialists and an external test set (N = 300) from University of Southern California clinics. Performance was assessed while varying training set size and stratifying by demographic factors. xRAI was used for saliency mapping.</div></div><div><h3>Main Outcome Measures</h3><div>Area under the receiver operating characteristic curve (AUC–ROC) and threshold-specific metrics.</div></div><div><h3>Results</h3><div>The cropped image VGG-19 model achieved the highest AUC–ROC (0.924 [0.907–0.940]), which was comparable (<em>P</em> = 0.07) to the cropped image RETFound model (0.911 [0.892–0.930]), which achieved the highest Youden-optimal performance (sensitivity 82.6% and specificity 88.2%) and F1 score (0.801). Cropped image models outperformed their uncropped counterparts (RETFound 0.889 [0.868–0.909], VGG-19 0.898 [0.879–0.917]) within each architecture (<em>P</em> < 0.001 for AUC–ROC comparisons). The uncropped image RETFound model performed best on external data (0.886 [0.849–0.924] vs. the next-highest 0.797 [0.746–0.848], <em>P</em> < 0.001 for AUC–ROC comparisons). RETFound models had a performance advantage when trained on smaller datasets (N < 2000 images), and the cropped image RETFound model performed consistently across ethnic groups (<em>P</em> = 0.20), whereas the others did not (<em>P</em> < 0.04). Performance did not vary by age or gender. Saliency maps for both architectures consistently included the optic nerve.</div></div><div><h3>Conclusions</h3><div>Although both RETFound and VGG-19 models performed well for classification of referable glaucoma, foundation models may be preferable when training data are limited and when domain shift is expected. Training models using images cropped to the region of the optic nerve improves performance regardless of architecture but may reduce model generalizability.</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 101008"},"PeriodicalIF":4.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884504","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 : 2025-11-11DOI: 10.1016/j.xops.2025.101004
Taiga Inooka MD, PhD , Hikaru Ota MD, PhD , Yosuke Taki MD, PhD, Sayuri Yasuda MD, PhD, Ai Fujita Sajiki MD, PhD, Ayana Suzumura MD, PhD, Hideyuki Shimizu MD, PhD, Jun Takeuchi MD, PhD, Ryo Tomita MD, PhD, Taro Kominami MD, PhD, Hiroaki Ushida MD, PhD, Kenya Yuki MD, PhD, Koji M. Nishiguchi MD, PhD
<div><h3>Objective</h3><div>Artificial intelligence–powered large language models (LLMs) are increasingly applied in health care. However, studies in ophthalmology assessing whether LLMs can improve the accuracy of complex differential diagnoses in clinical cases, or which levels of clinical experience benefit most from their use, remain lacking. This study assessed the effectiveness of ChatGPT-4o, an LLM-driven chatbot, in enhancing ophthalmologists' clinical reasoning using original scenarios.</div></div><div><h3>Design</h3><div>Prospective study.</div></div><div><h3>Subjects</h3><div>Ten original ophthalmic clinical scenarios with open-ended questions were developed, covering the following subspecialties: oculoplastic and orbital disease, glaucoma, inherited retinal disease, macular disease, neuro-ophthalmology, ocular surface, pediatric ophthalmology, retinal vascular disease, strabismus, and uveitis.</div></div><div><h3>Methods</h3><div>Responses to each clinical scenario were collected from 20 ophthalmologists (10 residents and 10 board-certified ophthalmologists) and ChatGPT-4o. Ophthalmologists subsequently revised their answers with assistance from ChatGPT-4o. All responses were anonymized and independently evaluated by 3 attending ophthalmologists based on 4 metrics: coherency, factuality, comprehensiveness, and safety (each on a 5-point scale).</div></div><div><h3>Main Outcome Measures</h3><div>The median total scores for each group in coherency, factuality, comprehensiveness, and safety (maximum of 15 points each).</div></div><div><h3>Results</h3><div>Assistance from ChatGPT-4o significantly improved evaluation scores for coherency, comprehensiveness, and safety among both residents and board-certified ophthalmologists (all, <em>P</em> < 0.001). However, factuality scores showed no significant improvements (<em>P</em> = 0.114 and 0.839, respectively). Although ChatGPT-4o assistance increased citation frequency (residents: 0.24–0.98 per response, board-certified ophthalmologists: 0.12–0.68 per response, both <em>P</em> < 0.05), approximately 44% of these additional citations were identified as hallucinated references, nonexistent, or incorrect citations. Notably, ChatGPT-4o assistance led to a significant increase in variability for factuality and safety scores in both groups (Brown–Forsythe test, all <em>P</em> < 0.05), whereas it decreased variability for coherency and comprehensiveness, with the reduction statistically significant among residents (<em>P</em> = 0.008 and <em>P</em> = 0.006, respectively).</div></div><div><h3>Conclusions</h3><div>ChatGPT-4o effectively enhanced diagnostic reasoning and response quality, particularly among ophthalmology residents. However, successful integration into clinical education and practice requires careful management of increased variability in factuality and safety. This issue could be addressed by implementing strategies such as advanced retrieval-augmented generation systems to ens
{"title":"Evolving Consultation: Enhancing Ophthalmic Diagnostic Performance Using Large Language Model","authors":"Taiga Inooka MD, PhD , Hikaru Ota MD, PhD , Yosuke Taki MD, PhD, Sayuri Yasuda MD, PhD, Ai Fujita Sajiki MD, PhD, Ayana Suzumura MD, PhD, Hideyuki Shimizu MD, PhD, Jun Takeuchi MD, PhD, Ryo Tomita MD, PhD, Taro Kominami MD, PhD, Hiroaki Ushida MD, PhD, Kenya Yuki MD, PhD, Koji M. Nishiguchi MD, PhD","doi":"10.1016/j.xops.2025.101004","DOIUrl":"10.1016/j.xops.2025.101004","url":null,"abstract":"<div><h3>Objective</h3><div>Artificial intelligence–powered large language models (LLMs) are increasingly applied in health care. However, studies in ophthalmology assessing whether LLMs can improve the accuracy of complex differential diagnoses in clinical cases, or which levels of clinical experience benefit most from their use, remain lacking. This study assessed the effectiveness of ChatGPT-4o, an LLM-driven chatbot, in enhancing ophthalmologists' clinical reasoning using original scenarios.</div></div><div><h3>Design</h3><div>Prospective study.</div></div><div><h3>Subjects</h3><div>Ten original ophthalmic clinical scenarios with open-ended questions were developed, covering the following subspecialties: oculoplastic and orbital disease, glaucoma, inherited retinal disease, macular disease, neuro-ophthalmology, ocular surface, pediatric ophthalmology, retinal vascular disease, strabismus, and uveitis.</div></div><div><h3>Methods</h3><div>Responses to each clinical scenario were collected from 20 ophthalmologists (10 residents and 10 board-certified ophthalmologists) and ChatGPT-4o. Ophthalmologists subsequently revised their answers with assistance from ChatGPT-4o. All responses were anonymized and independently evaluated by 3 attending ophthalmologists based on 4 metrics: coherency, factuality, comprehensiveness, and safety (each on a 5-point scale).</div></div><div><h3>Main Outcome Measures</h3><div>The median total scores for each group in coherency, factuality, comprehensiveness, and safety (maximum of 15 points each).</div></div><div><h3>Results</h3><div>Assistance from ChatGPT-4o significantly improved evaluation scores for coherency, comprehensiveness, and safety among both residents and board-certified ophthalmologists (all, <em>P</em> < 0.001). However, factuality scores showed no significant improvements (<em>P</em> = 0.114 and 0.839, respectively). Although ChatGPT-4o assistance increased citation frequency (residents: 0.24–0.98 per response, board-certified ophthalmologists: 0.12–0.68 per response, both <em>P</em> < 0.05), approximately 44% of these additional citations were identified as hallucinated references, nonexistent, or incorrect citations. Notably, ChatGPT-4o assistance led to a significant increase in variability for factuality and safety scores in both groups (Brown–Forsythe test, all <em>P</em> < 0.05), whereas it decreased variability for coherency and comprehensiveness, with the reduction statistically significant among residents (<em>P</em> = 0.008 and <em>P</em> = 0.006, respectively).</div></div><div><h3>Conclusions</h3><div>ChatGPT-4o effectively enhanced diagnostic reasoning and response quality, particularly among ophthalmology residents. However, successful integration into clinical education and practice requires careful management of increased variability in factuality and safety. This issue could be addressed by implementing strategies such as advanced retrieval-augmented generation systems to ens","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101004"},"PeriodicalIF":4.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798003","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 : 2025-11-11DOI: 10.1016/j.xops.2025.101003
Stephen J. Kim MD , Sapna S. Gangaputra MD, MPH , Sara Al Hussein Al Awamlh MD , Leena Choi PhD , Elizabeth A. McNeer MS , Jinsong Sheng MD
<div><h3>Objective</h3><div>We analyzed the cross-sectional associations of 24 inflammatory cytokines with diabetic retinopathy (DR) severity.</div></div><div><h3>Design</h3><div>Prospective, clinical trial at a tertiary academic medical center.</div></div><div><h3>Subjects</h3><div>Three hundred twenty-eight eyes of 164 patients with diabetes with varying severity of DR, including none.</div></div><div><h3>Methods</h3><div>All diabetic eyes had aqueous sampling of both eyes, ETDRS visual acuity, and color fundus photographs. Three groups were enrolled according to grading of baseline color fundus photographs: 23 (46 eyes) patients with diabetes with no DR, 118 (236 eyes) patients with diabetes with moderate nonproliferative DR (NPDR), and 23 (46 eyes) patients with diabetes with proliferative DR. The moderate NPDR group was further subdivided into mild–moderate and moderate–severe groups based on the ETDRS severity scale. Blood was drawn to measure hemoglobin A1c. A microparticle bead-based multiplex assay was used to measure: fibroblast growth factor-2, eotaxin, granulocyte colony-stimulating factor, FMS-like tyrosine kinase 3, GRO, interleukin (IL)-10, monocyte chemotactic protein (MCP)-3, macrophage-derived chemokine, soluble CD40L, IL-17A, IL-1 receptor antagonist, IL-1β, IL-2, IL-4, IL-6, IL-8, induced protein 10, MCP-1, macrophage inflammatory protein-1β, tumor necrosis factor-α, VEGF-A, regulated on activation normal T expressed and secreted, and platelet-derived growth factor-AA and -AB/BB. Triplicate testing of all cytokines was performed.</div></div><div><h3>Main Outcome Measures</h3><div>Aqueous cytokines, DR severity, hemoglobin A1c.</div></div><div><h3>Results</h3><div>Median and interquartile ranges of VEGF-A by grade of eye were 100.57 (80.93–145.67), 153.40 (112.86–206.24), 223.45 (135.27–319.21), and 295.60 (177.46–388.89) pg/mL among no DR, mild–moderate NPDR, moderate–severe NPDR, and proliferative DR groups, respectively. Median and interquartile ranges of IL-6 were 5.45 (3.16–7.86), 8.28 (4.78–20.68), 12.80 (8.24–27.49), and 17.14 (10.31–52.61) pg/mL and of IL-8 were 7.06 (4.10–13.08), 10.53 (6.45–15.85), 16.25 (11.61–24.10), and 20.61 (14.00–27.65) pg/mL among no DR, mild–moderate NPDR, moderate–severe NPDR, and proliferative DR groups, respectively. Similar positive linear relationships were seen with IL-4 and MCP-1. Compared with the no DR group, significant progressive odds ratios were observed among all DR severity groups for VEGF-A, IL-6, IL-8, and IL-4. Significant progressive odds ratios from mild–moderate NPDR to moderate–severe NPDR were observed for FMS-like tyrosine kinase 3, IL-10, induced protein 10, MCP-1, macrophage-derived chemokine, and platelet-derived growth factor-AA. The majority of cytokines demonstrated no relationship with hemoglobin A1c.</div></div><div><h3>Conclusions</h3><div>We report that several key inflammatory cytokines demonstrate cross-sectional associations with DR severity. Our results le
{"title":"INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy Study","authors":"Stephen J. Kim MD , Sapna S. Gangaputra MD, MPH , Sara Al Hussein Al Awamlh MD , Leena Choi PhD , Elizabeth A. McNeer MS , Jinsong Sheng MD","doi":"10.1016/j.xops.2025.101003","DOIUrl":"10.1016/j.xops.2025.101003","url":null,"abstract":"<div><h3>Objective</h3><div>We analyzed the cross-sectional associations of 24 inflammatory cytokines with diabetic retinopathy (DR) severity.</div></div><div><h3>Design</h3><div>Prospective, clinical trial at a tertiary academic medical center.</div></div><div><h3>Subjects</h3><div>Three hundred twenty-eight eyes of 164 patients with diabetes with varying severity of DR, including none.</div></div><div><h3>Methods</h3><div>All diabetic eyes had aqueous sampling of both eyes, ETDRS visual acuity, and color fundus photographs. Three groups were enrolled according to grading of baseline color fundus photographs: 23 (46 eyes) patients with diabetes with no DR, 118 (236 eyes) patients with diabetes with moderate nonproliferative DR (NPDR), and 23 (46 eyes) patients with diabetes with proliferative DR. The moderate NPDR group was further subdivided into mild–moderate and moderate–severe groups based on the ETDRS severity scale. Blood was drawn to measure hemoglobin A1c. A microparticle bead-based multiplex assay was used to measure: fibroblast growth factor-2, eotaxin, granulocyte colony-stimulating factor, FMS-like tyrosine kinase 3, GRO, interleukin (IL)-10, monocyte chemotactic protein (MCP)-3, macrophage-derived chemokine, soluble CD40L, IL-17A, IL-1 receptor antagonist, IL-1β, IL-2, IL-4, IL-6, IL-8, induced protein 10, MCP-1, macrophage inflammatory protein-1β, tumor necrosis factor-α, VEGF-A, regulated on activation normal T expressed and secreted, and platelet-derived growth factor-AA and -AB/BB. Triplicate testing of all cytokines was performed.</div></div><div><h3>Main Outcome Measures</h3><div>Aqueous cytokines, DR severity, hemoglobin A1c.</div></div><div><h3>Results</h3><div>Median and interquartile ranges of VEGF-A by grade of eye were 100.57 (80.93–145.67), 153.40 (112.86–206.24), 223.45 (135.27–319.21), and 295.60 (177.46–388.89) pg/mL among no DR, mild–moderate NPDR, moderate–severe NPDR, and proliferative DR groups, respectively. Median and interquartile ranges of IL-6 were 5.45 (3.16–7.86), 8.28 (4.78–20.68), 12.80 (8.24–27.49), and 17.14 (10.31–52.61) pg/mL and of IL-8 were 7.06 (4.10–13.08), 10.53 (6.45–15.85), 16.25 (11.61–24.10), and 20.61 (14.00–27.65) pg/mL among no DR, mild–moderate NPDR, moderate–severe NPDR, and proliferative DR groups, respectively. Similar positive linear relationships were seen with IL-4 and MCP-1. Compared with the no DR group, significant progressive odds ratios were observed among all DR severity groups for VEGF-A, IL-6, IL-8, and IL-4. Significant progressive odds ratios from mild–moderate NPDR to moderate–severe NPDR were observed for FMS-like tyrosine kinase 3, IL-10, induced protein 10, MCP-1, macrophage-derived chemokine, and platelet-derived growth factor-AA. The majority of cytokines demonstrated no relationship with hemoglobin A1c.</div></div><div><h3>Conclusions</h3><div>We report that several key inflammatory cytokines demonstrate cross-sectional associations with DR severity. Our results le","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101003"},"PeriodicalIF":4.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798067","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 : 2025-11-11DOI: 10.1016/j.xops.2025.100998
Lynn Kandakji PhD , Shafi Balal MBBS , Aleksander Stupnicki iBSc , Siyin Liu MBBS, PhD , Marcello Leucci BOptom , Dan Gore MD , Bruce Allan MD , Nikolas Pontikos PhD
Purpose
To objectively identify subclinical keratoconus (SKC) from a large sample of healthy and keratoconus (KC) patients via a data-driven framework on corneal imaging data from an anterior-segment OCT (AS-OCT) device (MS-39, CSO Italia).
Design
A retrospective cohort study.
Subjects
At 2 sites within the Moorfields Eye Hospital network in London, United Kingdom, 25 816 corneal scans from 5005 patients, including 3605 with KC and 1400 healthy control patients, were acquired between 2020 and 2024.
Methods
Principal component analysis (PCA) followed by Gaussian mixture modeling (GMM) was applied to AS-OCT–derived data, including 20 KC indices and patient age, to identify SKC eyes, which were then statistically compared against healthy and KC eyes. Subclinical KC eyes were also validated against external systems including same-day Pentacam (Oculus Optikgeräte) scans, Belin-Ambrosio’s ABCD system, KC progression criteria determined by a panel of corneal specialists, and the Moorfields Corneal Cross-linking (CXL) Risk Calculator.
Main Outcome Measures
Detection of SKC and progression of these eyes to clinically diagnosable KC over time.
Results
The GMM identified 166 eyes from 161 patients with distinct structural differences between healthy and KC eyes. These eyes clustered in the morphometric transition zone in PCA space and were predominantly classified as ABCD stage 0. However, they demonstrated asymmetry with their fellow eye, higher predicted CXL risk at 1–4 years (P < 0.001), and faster progression to KC (log-rank P < 0.0001) compared with healthy eyes. Among SKC eyes with longitudinal data, 72.7% met Global Consensus criteria for progression.
Conclusions
Subclinical KC remains challenging to detect, and although classic staging such as ABCD retains clinical utility, it is insufficient for early disease detection. Principal component analysis followed by GMM classification on a multidimensional AS-OCT dataset identifies a distinct and high-risk SKC group. This semisupervised framework offers a complementary tool for early risk stratification and can be applied to new patients via projection into the learned PCA space and computation of KC probability. Threshold values corresponding to the 25th and 75th percentiles of KC probability for each parameter may serve as clinical context for flagging eyes when multiple features fall in the atypical range.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Data-Driven Detection of Subclinical Keratoconus via Semi-Supervised Clustering of Multidimensional Corneal Biomarkers","authors":"Lynn Kandakji PhD , Shafi Balal MBBS , Aleksander Stupnicki iBSc , Siyin Liu MBBS, PhD , Marcello Leucci BOptom , Dan Gore MD , Bruce Allan MD , Nikolas Pontikos PhD","doi":"10.1016/j.xops.2025.100998","DOIUrl":"10.1016/j.xops.2025.100998","url":null,"abstract":"<div><h3>Purpose</h3><div>To objectively identify subclinical keratoconus (SKC) from a large sample of healthy and keratoconus (KC) patients via a data-driven framework on corneal imaging data from an anterior-segment OCT (AS-OCT) device (MS-39, CSO Italia).</div></div><div><h3>Design</h3><div>A retrospective cohort study.</div></div><div><h3>Subjects</h3><div>At 2 sites within the Moorfields Eye Hospital network in London, United Kingdom, 25 816 corneal scans from 5005 patients, including 3605 with KC and 1400 healthy control patients, were acquired between 2020 and 2024.</div></div><div><h3>Methods</h3><div>Principal component analysis (PCA) followed by Gaussian mixture modeling (GMM) was applied to AS-OCT–derived data, including 20 KC indices and patient age, to identify SKC eyes, which were then statistically compared against healthy and KC eyes. Subclinical KC eyes were also validated against external systems including same-day Pentacam (Oculus Optikgeräte) scans, Belin-Ambrosio’s ABCD system, KC progression criteria determined by a panel of corneal specialists, and the Moorfields Corneal Cross-linking (CXL) Risk Calculator.</div></div><div><h3>Main Outcome Measures</h3><div>Detection of SKC and progression of these eyes to clinically diagnosable KC over time.</div></div><div><h3>Results</h3><div>The GMM identified 166 eyes from 161 patients with distinct structural differences between healthy and KC eyes. These eyes clustered in the morphometric transition zone in PCA space and were predominantly classified as ABCD stage 0. However, they demonstrated asymmetry with their fellow eye, higher predicted CXL risk at 1–4 years (<em>P</em> < 0.001), and faster progression to KC (log-rank <em>P</em> < 0.0001) compared with healthy eyes. Among SKC eyes with longitudinal data, 72.7% met Global Consensus criteria for progression.</div></div><div><h3>Conclusions</h3><div>Subclinical KC remains challenging to detect, and although classic staging such as ABCD retains clinical utility, it is insufficient for early disease detection. Principal component analysis followed by GMM classification on a multidimensional AS-OCT dataset identifies a distinct and high-risk SKC group. This semisupervised framework offers a complementary tool for early risk stratification and can be applied to new patients via projection into the learned PCA space and computation of KC probability. Threshold values corresponding to the 25th and 75th percentiles of KC probability for each parameter may serve as clinical context for flagging eyes when multiple features fall in the atypical range.</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 2","pages":"Article 100998"},"PeriodicalIF":4.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749032","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 : 2025-11-11DOI: 10.1016/j.xops.2025.101005
Yusong Zhou MD , Qingqing Ye MB , Xuan Qiu MD, PhD , Zixuan Xu MD, Yunsi He MD, Ying Yao MD, Yangfei Pang MD, Wentong Yu MD, Yudan Zhong MM, Qiuying Li MM, Lei Feng MB, Junpeng Yuan BS, Yun Wen MD, PhD, Zhonghao Wang MD, Jinrong Li MD, PhD
Purpose
Perceptual learning (PL) is a novel therapeutic approach for the treatment of amblyopia. This study evaluated whether extending the duration of PL could yield sustained therapeutic benefits in amblyopia management.
Design
A retrospective observational design.
Methods
Analysis included 93 of 100 patients who completed 6-month lateral masking PL and had 3- or 6-month follow-up data. Missing data were handled using multiple imputation by chained equations. Longitudinal changes in visual function—including best-corrected visual acuity (BCVA), contrast sensitivity function (CSF), and stereopsis—were evaluated using a linear mixed-effects model. To identify factors associated with improvements in BCVA and area under the log CSF (AULCSF), multivariable linear regression models were constructed, incorporating all relevant covariates selected based on clinical significance and evidence from existing literature. Only 1 amblyopic eye per patient was included in the analysis of BCVA and AULCSF. In cases of bilateral amblyopia, the worse eye was selected for the primary analysis. Sensitivity analyses were conducted in 2 ways: (1) using measurements from the better eye and (2) using datasets in which missing values had been imputed based on logical rules; the missing value was replaced with the worse outcome of the 2 observed values from the remaining time points.
Main Outcome Measures
Measurements included BCVA, CSF, and stereoacuity.
Results
A total of 93 participants (46 males and 47 females) were enrolled, with a mean age of 15.3 ± 8.3 years. Amblyopia subtypes included: isoametropic (n = 8), anisometropic (n = 63), strabismic (n = 12), deprivation (n = 1), and mixed (n = 9). Analysis revealed significant and sustained improvements in both BCVA and the AULCSF. Near stereopsis also improved following 3 months of PL training. However, further extension of the training duration did not result in additional significant gains in stereopsis. Multivariable linear regression analysis indicated that initial baseline visual function and history of occlusion therapy were the primary factors associated with the improvement of BCVA and AULCSF.
Conclusions
Perceptual learning treatment can improve the visual function of amblyopia patients. Considering that extending the duration of PL still resulted in measurable visual improvements, a 6-month training of PL appears to be necessary.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Extending Treatment Duration in Perceptual Learning for Amblyopia","authors":"Yusong Zhou MD , Qingqing Ye MB , Xuan Qiu MD, PhD , Zixuan Xu MD, Yunsi He MD, Ying Yao MD, Yangfei Pang MD, Wentong Yu MD, Yudan Zhong MM, Qiuying Li MM, Lei Feng MB, Junpeng Yuan BS, Yun Wen MD, PhD, Zhonghao Wang MD, Jinrong Li MD, PhD","doi":"10.1016/j.xops.2025.101005","DOIUrl":"10.1016/j.xops.2025.101005","url":null,"abstract":"<div><h3>Purpose</h3><div>Perceptual learning (PL) is a novel therapeutic approach for the treatment of amblyopia. This study evaluated whether extending the duration of PL could yield sustained therapeutic benefits in amblyopia management.</div></div><div><h3>Design</h3><div>A retrospective observational design.</div></div><div><h3>Methods</h3><div>Analysis included 93 of 100 patients who completed 6-month lateral masking PL and had 3- or 6-month follow-up data. Missing data were handled using multiple imputation by chained equations. Longitudinal changes in visual function—including best-corrected visual acuity (BCVA), contrast sensitivity function (CSF), and stereopsis—were evaluated using a linear mixed-effects model. To identify factors associated with improvements in BCVA and area under the log CSF (AULCSF), multivariable linear regression models were constructed, incorporating all relevant covariates selected based on clinical significance and evidence from existing literature. Only 1 amblyopic eye per patient was included in the analysis of BCVA and AULCSF. In cases of bilateral amblyopia, the worse eye was selected for the primary analysis. Sensitivity analyses were conducted in 2 ways: (1) using measurements from the better eye and (2) using datasets in which missing values had been imputed based on logical rules; the missing value was replaced with the worse outcome of the 2 observed values from the remaining time points.</div></div><div><h3>Main Outcome Measures</h3><div>Measurements included BCVA, CSF, and stereoacuity.</div></div><div><h3>Results</h3><div>A total of 93 participants (46 males and 47 females) were enrolled, with a mean age of 15.3 ± 8.3 years. Amblyopia subtypes included: isoametropic (n = 8), anisometropic (n = 63), strabismic (n = 12), deprivation (n = 1), and mixed (n = 9). Analysis revealed significant and sustained improvements in both BCVA and the AULCSF. Near stereopsis also improved following 3 months of PL training. However, further extension of the training duration did not result in additional significant gains in stereopsis. Multivariable linear regression analysis indicated that initial baseline visual function and history of occlusion therapy were the primary factors associated with the improvement of BCVA and AULCSF.</div></div><div><h3>Conclusions</h3><div>Perceptual learning treatment can improve the visual function of amblyopia patients. Considering that extending the duration of PL still resulted in measurable visual improvements, a 6-month training of PL appears to be necessary.</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 2","pages":"Article 101005"},"PeriodicalIF":4.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884505","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}