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The Effect of Optic Nerve Crush on Lens-Induced Myopia in Mice 视神经压迫对小鼠晶状体性近视的影响
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-20 DOI: 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.
目的屈光发展的潜在机制-它是否局限于局部眼球或涉及中央视觉通路-仍然存在争议。本研究旨在探讨视神经压迫(ONC)对小鼠屈光发育和晶状体性近视(LIM)的影响及其可能机制。设计实验室实验研究。实验对象:采用3周龄C57BL/6小鼠。将动物分为以下实验组:ONC组与假手术(sham)组;ONC联合LIM (ONC-LIM)组与SHAM联合LIM (SHAM-LIM)组;LIM接着是ONC组、LIM组和plano lens组。方法测定屈光度和眼生物学参数。对ONC组和SHAM组的视网膜进行大量rna测序分析。采用edgeR进行组间差异表达分析。通过趋势分析选择差异表达基因,探讨ONC术后不同屈光条件下的表达趋势。进行京都基因与基因组百科全书富集、蛋白-蛋白互作分析、基因集富集分析,并应用定量逆转录聚合酶链反应进行验证。主要观察指标轴向长度(AL)。结果ONC后,50%的小鼠出现近视移位,25%的小鼠出现远视移位,AL的变化与屈光一致。与SHAM-LIM组不同,ONC- lim组未发生近视移位或轴向伸长,提示ONC后光学离焦不会引起小鼠近视移位。rna测序分析揭示了与onc后屈光状态相关的几种途径,包括谷氨酸能突触、促性腺激素释放激素信号传导和长期抑郁。结论完整的视神经对于正常小鼠的视力矫正和LIM的发展是必要的。虽然局部眼部机制仍然是屈光调节的既定范例,但我们的实验结果表明中枢神经系统通路可能参与眼部生长调节。需要进一步的研究来阐明地方和中央监管系统之间的确切机制和潜在的相互作用。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。
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引用次数: 0
OCT-PRO: A Multimodal Model Integrating OCT and Clinical Traits to Predict Postoperative Outcomes in Cataract Patients OCT- pro:综合OCT和临床特征预测白内障患者术后预后的多模式模型
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-17 DOI: 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。
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引用次数: 0
Risk Factors for Adult Axial Length Elongation: A 5-Year Population-Based Cohort Study 成人轴长延长的危险因素:一项基于5年人群的队列研究
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-17 DOI: 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.
目的:成人轴长(AL)延长与病理结果相关;然而,基于人群的纵向证据仍然有限,实用的风险分析尚不清楚。我们的目的是量化成人AL延长的患病率和年增长率,并在基于人群的健康检查队列中确定独立的决定因素。设计:回顾性、单中心队列研究。受试者:共有4016名年龄在22.4至93.0岁之间的成年人(8032只眼睛,21421次就诊)接受了日本健康检查项目,中位随访时间为5.31年。方法用眼内线性回归斜率估计每只眼的AL年变化(mm/年),并将其分为重度(≥0.10)、中度(≥0.05 ~ 0.10)、轻度(≥0.00 ~ 0.05)和零(<0)。使用类别加权比例-几率顺序逻辑模型评估关联。配对水平的变化点分析模拟了哪只眼睛拉长得更快。主要结局指标:按年度AL伸长严重程度、更严重伸长决定因素的调整优势比(ORs)以及基线-AL交叉点计算的眼睛比例,在该交叉点上,较长的眼睛更有可能伸长得更快。结果轻度、轻度眼占98.6%;中度和重度不常见(1.3%和0.2%)。严重程度较高的独立决定因素包括基线AL较长(OR, 1.34 / 1 mm), AL的眼间差异较大(OR, 7.18 / 1 mm),近视黄斑病变包括眼底块化(OR, 2.79)和女性(OR, 3.05)。变化点分析确定了长眼在28.56 mm附近的交叉点:低于这个值,它会延长得更快的估计概率约为0.50(没有一致的横向偏好),而高于它的概率超过0.50,在高基线AL值下具有很大的不确定性。结论成人AL伸长罕见且缓慢;风险集中在AL较长、眼轴不对称、近视黄斑病变和成年女性。这些易于测量的特征可以为健康检查设置的后续决策提供信息;对眼角膜水平的估计约为28.6毫米,这可能有助于确定随访的优先顺序,但应谨慎解释。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":"Risk Factors for Adult Axial Length Elongation: A 5-Year Population-Based Cohort Study","authors":"Taiga Inooka MD, PhD ,&nbsp;Yuki Kimura MD ,&nbsp;Shota Fujikawa ,&nbsp;Sayuri Yasuda MD, PhD ,&nbsp;Taro Kominami MD, PhD ,&nbsp;Tetsuhito Kojima MD, PhD ,&nbsp;Shinji Ueno MD, PhD ,&nbsp;Yasuki Ito MD, PhD ,&nbsp;Koji M. Nishiguchi MD, PhD ,&nbsp;Kenya Yuki MD, PhD","doi":"10.1016/j.xops.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 &lt;0.10), mild (≥0.00 to &lt;0.05), or nil (&lt;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}
引用次数: 0
Results from a Phase I Extension Study of Ciliary Neurotrophic Factor in Patients with Macular Telangiectasia Type 2 睫状神经营养因子在2型黄斑毛细血管扩张患者中的I期扩展研究结果
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-14 DOI: 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.
目的主要评估NT-501 (revakinagene taroretcel-lwey)治疗2型黄斑毛细血管扩张(MacTel)的长期安全性和视网膜成像结果,该药物可在较长时间内向玻璃体释放睫状体神经营养因子。设计I期非随机、多中心、开放标签扩展研究。参与者:6名完成了为期60个月的I期临床研究的双侧MacTel患者。方法在母体研究中,参与者通过手术将NT-501植入研究眼。病情更严重的那只眼被确定为研究用眼。为了这项扩展研究的目的,同伴眼提供了未经处理的自然历史数据。扩展研究包括种植后72、84、96和108个月的访问。主要结局指标:安全性结局包括不良事件(ae)、最佳矫正视力(BCVA)较基线值的变化,以及BCVA较基线值损失≥10或≥15个字母的眼睛比例。视网膜成像变量包括椭球区(EZ)(内段/外段)面积损失与基线相比的变化,以及EZ面积损失较基线增加≥35%的研究眼比例。结果所有种植体在最后的研究访问中均被保留。所有眼部治疗出现的ae均为轻至中度;没有一例导致研究中止。在任何研究访问时,没有研究眼的BCVA从基线下降≥15个字母。同样,在72、84和96个月时,没有研究眼睛出现≥10个字母的丢失;1只研究眼(17%)在108个月时出现。相对于其他眼睛(范围,75%-100%),EZ面积损失较基线增加≥35%的研究眼睛的比例较低(范围,50%-60%)。结论在9年的随访期内,NT-501具有良好的耐受性和安全性。NT-501治疗MacTel的长期疗效的进一步研究正在进行中。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。
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引用次数: 0
Differentiation Between Moderate Versus High Myopia: The 2-Continent Eye Study 中度和高度近视的区分:两大洲眼科研究
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-12 DOI: 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.
目的探讨中度近视与高度近视视轴长度与近视性黄斑变性(MMD)患病率相关性的临界值。在俄罗斯、中国和印度进行的基于人群的设计研究。该项目包括以人群为基础的调查,包括北京眼科研究(n = 3325,年龄:40+岁)、俄罗斯乌拉尔眼科和医学研究(n = 5586,年龄:40+岁)、乌拉尔高龄研究(n = 541,年龄:85+岁)和乌拉尔儿童眼科研究(n = 4255,年龄:6+岁),以及印度中部眼科和医学研究(n = 4467,年龄:30+岁)。方法对患者进行眼底摄影、眼部生物特征等常规医学检查和眼科检查。根据病理性近视研究组的meta分析定义近视黄斑变性。主要观察指标MMD的发生率与轴长有关。结果共纳入36 123只眼(18 471例),年龄47.4±23.4岁,年龄范围6 ~ 100岁,眼轴长度23.2±1.1 mm,年龄范围18.22 ~ 34.20 mm。在整个研究人群中,较高的烟雾病分期与轴长(β: 0.55; B: 0.14; 95%可信区间[CI]: 0.14 - 0.15; P < 0.001)、年龄较大(β: 0.09; B: 0.001; 95% CI: 0.001 - 0.001; P < 0.001)、女性(β: 0.12; B: 0.07; 95% CI: 0.06-0.07; P < 0.001)和印度种族(β: 0.10; B: 0.07; 95% CI: 0.06-0.07; P < 0.001)相关。较高的MMD 2+期和3+期患病率与较长的轴长(比值比[OR]: 9.10; 95% CI: 6.93-11.9; P <; 0.001和OR: 6.90; 95% CI: 5.14-9.26; P <; 0.001和OR: 1.08; 95% CI: 1.05-1.11; P < 0.001)、较大的年龄(OR: 1.06; 95% CI: 2.70-17.9; P <; 0.001和OR: 3.69; 95% CI: 1.26-10.8; P = 0.02)和印度裔(OR: 6.96; 95% CI: 2.70-17.9; P <; 0.001和OR: 3.69; 95% CI: 1.26-10.8; P = 0.02)相关。轴长与2+期和3+期MMD患病率相关性回归曲线的拐点分别位于26.0 ~ 26.5 mm之间。结论中度和高度近视的眼轴长度相关临界值分别约为26.0和26.5 mm,年龄越小,MMD 2+期和3+期患病率越高。近视黄斑变性的患病率在印度人群中较高。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。
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引用次数: 0
Comparison of RETFound and a Supervised Convolutional Neural Network for Detection of Referable Glaucoma from Fundus Photographs retfind与监督卷积神经网络检测眼底照片中可参考青光眼的比较
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-12 DOI: 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.
目的比较基于视觉变压器的基础模型(RETFound)和监督卷积神经网络(VGG-19)对眼底照片中可参考青光眼的检测效果。设计诊断技术的评价。参与者来自洛杉矶县卫生服务部门远程筛查项目的66116名参与者。方法由验光师对可参考青光眼(杯盘比≥0.6)眼底照片进行标记。使用2种架构对裁剪和未裁剪的图像(训练N = 8996;验证N = 3002)训练了四个深度学习模型:RETFound,眼底照片自监督预训练的视觉转换器和VGG-19。模型在由青光眼专家标记的支架测试集(N = 1000)和来自南加州大学诊所的外部测试集(N = 300)上进行评估。性能评估时,不同的训练集大小和人口因素分层。xRAI用于显著性映射。主要结果测量:受试者工作特征曲线(AUC-ROC)和阈值特定指标下的面积。结果裁剪后的图像VGG-19模型AUC-ROC最高(0.924[0.907-0.940]),与裁剪后的图像RETFound模型(0.911[0.892-0.930])相当(P = 0.07),且具有最高的约登最优性能(灵敏度82.6%,特异性88.2%)和F1评分(0.801)。裁剪后的图像模型在每个架构内的表现都优于未裁剪的图像模型(RETFound 0.889 [0.868-0.909], VGG-19 0.898 [0.879-0.917]) (AUC-ROC比较的P <; 0.001)。未裁剪的图像RETFound模型在外部数据上表现最好(0.886[0.849-0.924],其次是0.797 [0.746-0.848],AUC-ROC比较P <; 0.001)。RETFound模型在较小的数据集(N <; 2000张图像)上训练时具有性能优势,并且裁剪后的图像RETFound模型在种族群体中表现一致(P = 0.20),而其他模型则没有(P < 0.04)。表现没有因年龄或性别而异。两种结构的显著性图一致地包括视神经。结论RETFound模型和VGG-19模型对可参考青光眼的分类均有较好的效果,但在训练数据有限和有可能发生域移位的情况下,基础模型可能更可取。使用裁剪到视神经区域的图像来训练模型,无论结构如何,都可以提高性能,但可能会降低模型的泛化性。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":"Comparison of RETFound and a Supervised Convolutional Neural Network for Detection of Referable Glaucoma from Fundus Photographs","authors":"Kyle Bolo MD ,&nbsp;Tran Huy Nguyen MS ,&nbsp;Sreenidhi Iyengar MS ,&nbsp;Zhiwei Li MS ,&nbsp;Van Nguyen MD ,&nbsp;Brandon J. Wong MD ,&nbsp;Jiun L. Do MD, PhD ,&nbsp;Jose-Luis Ambite PhD ,&nbsp;Carl Kesselman PhD ,&nbsp;Lauren P. Daskivich MD ,&nbsp;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> &lt; 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> &lt; 0.001 for AUC–ROC comparisons). RETFound models had a performance advantage when trained on smaller datasets (N &lt; 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> &lt; 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}
引用次数: 0
Evolving Consultation: Enhancing Ophthalmic Diagnostic Performance Using Large Language Model 不断发展的咨询:使用大语言模型提高眼科诊断性能
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-11 DOI: 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
目的人工智能驱动的大型语言模型(llm)在医疗保健领域的应用越来越广泛。然而,在眼科研究中,评估llm是否可以提高临床病例中复杂鉴别诊断的准确性,或者从使用llm中获益最多的临床经验水平,仍然缺乏。本研究评估了llm驱动的聊天机器人chatgpt - 40在使用原始场景增强眼科医生临床推理方面的有效性。DesignProspective研究。受试者开发了10个具有开放式问题的原始眼科临床方案,涵盖以下亚专科:眼整形和眼窝疾病、青光眼、遗传性视网膜疾病、黄斑疾病、神经眼科、眼表、儿童眼科、视网膜血管疾病、斜视和葡萄膜炎。方法收集20名眼科医生(10名住院医师和10名执业眼科医生)和chatgpt - 40对每个临床情景的回答。眼科医生随后在chatgpt - 40的帮助下修改了他们的答案。所有的回答都是匿名的,并由3名主治眼科医生根据4项指标进行独立评估:一致性、真实性、全面性和安全性(每项指标为5分制)。各组在一致性、真实性、全面性和安全性方面的总得分中位数(每组最高15分)。结果chatgpt - 40的帮助显著提高了住院医师和委员会认证的眼科医生在一致性、全面性和安全性方面的评估得分(均P <; 0.001)。然而,事实性得分没有显著改善(P分别为0.114和0.839)。虽然chatgpt - 40帮助增加了引用频率(居民:每次回复0.24-0.98,委员会认证的眼科医生:每次回复0.12-0.68,P < 0.05),但这些额外的引用中约有44%被确定为幻觉参考,不存在或不正确的引用。值得注意的是,chatgpt - 40辅助导致两组中事实性和安全性得分的变异性显著增加(Brown-Forsythe测试,均P <; 0.05),而降低一致性和全面性的变异性,在居民中降低具有统计学意义(P = 0.008和P = 0.006分别)。结论atgpt - 40可有效提高诊断推理和反应质量,特别是在眼科住院医师中。然而,要成功地整合到临床教育和实践中,需要仔细管理事实和安全性方面日益增加的可变性。这一问题可以通过实施诸如先进的检索增强生成系统等战略来解决,以确保提供准确和安全的临床信息。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":"Evolving Consultation: Enhancing Ophthalmic Diagnostic Performance Using Large Language Model","authors":"Taiga Inooka MD, PhD ,&nbsp;Hikaru Ota MD, PhD ,&nbsp;Yosuke Taki MD, PhD,&nbsp;Sayuri Yasuda MD, PhD,&nbsp;Ai Fujita Sajiki MD, PhD,&nbsp;Ayana Suzumura MD, PhD,&nbsp;Hideyuki Shimizu MD, PhD,&nbsp;Jun Takeuchi MD, PhD,&nbsp;Ryo Tomita MD, PhD,&nbsp;Taro Kominami MD, PhD,&nbsp;Hiroaki Ushida MD, PhD,&nbsp;Kenya Yuki MD, PhD,&nbsp;Koji M. Nishiguchi MD, PhD","doi":"10.1016/j.xops.2025.101004","DOIUrl":"10.1016/j.xops.2025.101004","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Prospective study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;The median total scores for each group in coherency, factuality, comprehensiveness, and safety (maximum of 15 points each).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Assistance from ChatGPT-4o significantly improved evaluation scores for coherency, comprehensiveness, and safety among both residents and board-certified ophthalmologists (all, &lt;em&gt;P&lt;/em&gt; &lt; 0.001). However, factuality scores showed no significant improvements (&lt;em&gt;P&lt;/em&gt; = 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 &lt;em&gt;P&lt;/em&gt; &lt; 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 &lt;em&gt;P&lt;/em&gt; &lt; 0.05), whereas it decreased variability for coherency and comprehensiveness, with the reduction statistically significant among residents (&lt;em&gt;P&lt;/em&gt; = 0.008 and &lt;em&gt;P&lt;/em&gt; = 0.006, respectively).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;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}
引用次数: 0
INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy Study 炎症介质在糖尿病视网膜病变病理生理学研究中的作用
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-11 DOI: 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
目的分析24种炎症因子与糖尿病视网膜病变(DR)严重程度的横断面相关性。设计在三级学术医疗中心进行前瞻性临床试验。研究对象:164例糖尿病患者328只眼睛,有不同程度的DR,包括无DR。方法采用双眼水样、ETDRS视敏度和眼底彩色照片。根据基线眼底彩色照片分级入组:无DR的糖尿病患者23例(46眼),中度非增生性DR (NPDR)的糖尿病患者118例(236眼),伴有增生性DR的糖尿病患者23例(46眼)。中度NPDR组根据ETDRS严重程度量表进一步细分为轻中度组和中重度组。抽血测量糖化血红蛋白。采用微粒微珠多重测定法测定:成纤维细胞生长因子-2、eotaxin、粒细胞集落刺激因子、fms样酪氨酸激酶3、GRO、白细胞介素(IL)-10、单核细胞趋化蛋白(MCP)-3、巨噬细胞来源的趋化因子、可溶性CD40L、IL- 17a、IL-1受体拮抗剂、IL-1β、IL-2、IL-4、IL-6、IL-8、诱导蛋白10、MCP-1、巨噬细胞炎症蛋白-1β、肿瘤坏死因子-α、VEGF-A、活化正常T表达和分泌的调节因子- aa和-AB/BB。对所有细胞因子进行三次重复检测。主要观察指标:水细胞因子、DR严重程度、血红蛋白A1c。结果无DR组、轻中度NPDR组、中重度NPDR组和增生性DR组VEGF-A按眼部分级的中位数和四分位数范围分别为100.57(80.93-145.67)、153.40(112.86-206.24)、223.45(135.27-319.21)和295.60 (177.46-388.89)pg/mL。无DR、轻-中度NPDR、中-重度NPDR和增生性DR组IL-6的中位数和四分位数区间分别为5.45(3.16-7.86)、8.28(4.78-20.68)、12.80(8.24-27.49)和17.14 (10.31-52.61)pg/mL, IL-8的中位数和四分位数区间分别为7.06(4.10-13.08)、10.53(6.45-15.85)、16.25(11.61-24.10)和20.61 (14.00-27.65)pg/mL。IL-4和MCP-1之间也存在类似的正线性关系。与无DR组相比,在所有DR严重程度组中VEGF-A、IL-6、IL-8和IL-4的进展优势比均显著。观察到fms样酪氨酸激酶3、IL-10、诱导蛋白10、MCP-1、巨噬细胞来源的趋化因子和血小板来源的生长因子- aa从轻度至中度NPDR到中度至重度NPDR的渐进优势比显著。多数细胞因子与糖化血红蛋白无相关性。结论:我们报告了几种关键的炎症细胞因子与DR严重程度的横断面相关性。我们的研究结果支持炎症细胞因子是与DR严重程度相关的重要生物标志物的假设,并可能代表抑制的新靶点。作者在本文中讨论的任何材料中没有专有或商业利益。
{"title":"INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy Study","authors":"Stephen J. Kim MD ,&nbsp;Sapna S. Gangaputra MD, MPH ,&nbsp;Sara Al Hussein Al Awamlh MD ,&nbsp;Leena Choi PhD ,&nbsp;Elizabeth A. McNeer MS ,&nbsp;Jinsong Sheng MD","doi":"10.1016/j.xops.2025.101003","DOIUrl":"10.1016/j.xops.2025.101003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;We analyzed the cross-sectional associations of 24 inflammatory cytokines with diabetic retinopathy (DR) severity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Prospective, clinical trial at a tertiary academic medical center.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;Three hundred twenty-eight eyes of 164 patients with diabetes with varying severity of DR, including none.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Aqueous cytokines, DR severity, hemoglobin A1c.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;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}
引用次数: 0
Data-Driven Detection of Subclinical Keratoconus via Semi-Supervised Clustering of Multidimensional Corneal Biomarkers 基于半监督聚类的多维角膜生物标志物数据驱动检测亚临床圆锥角膜
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-11 DOI: 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.
目的通过对前段OCT (AS-OCT)设备(MS-39, CSO Italia)角膜成像数据的数据驱动框架,客观地从大量健康和圆锥角膜(KC)患者中识别亚临床圆锥角膜(SKC)。设计:回顾性队列研究。受试者在英国伦敦Moorfields眼科医院网络的2个站点,在2020年至2024年期间获得了5005名患者的25816次角膜扫描,其中包括3605名KC患者和1400名健康对照患者。方法采用主成分分析(PCA)和高斯混合建模(GMM)对as - oct数据进行分析,包括20个KC指标和患者年龄,以识别SKC眼,并与健康眼和KC眼进行统计比较。亚临床KC眼睛也通过外部系统进行验证,包括当天Pentacam (Oculus Optikgeräte)扫描,Belin-Ambrosio的ABCD系统,由角膜专家小组确定的KC进展标准,以及Moorfields角膜交联(CXL)风险计算器。随着时间的推移,SKC的检测和这些眼睛进展为临床诊断的KC。结果GMM从161例患者中鉴定出166只眼睛在健康眼和KC眼之间存在明显的结构差异。这些眼睛聚集在PCA空间的形态测量过渡区,主要被归类为ABCD 0期。然而,与健康的眼睛相比,他们表现出与同伴眼睛的不对称性,1-4年的预测CXL风险更高(P < 0.001),并且更快地进展为KC(对数秩P <; 0.0001)。在具有纵向数据的SKC眼中,72.7%符合全球共识的进展标准。结论亚临床KC的检测仍然具有挑战性,尽管ABCD等经典分期保留了临床应用价值,但不足以用于早期疾病检测。主成分分析之后,在多维AS-OCT数据集上进行GMM分类,确定了一个独特的高风险SKC组。这种半监督框架为早期风险分层提供了一种补充工具,可以通过投影到学习到的PCA空间和计算KC概率来应用于新患者。当多个特征落在非典型范围内时,每个参数对应的KC概率的第25和第75百分位数的阈值可以作为垂视的临床背景。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。
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引用次数: 0
Extending Treatment Duration in Perceptual Learning for Amblyopia 延长弱视知觉学习治疗时间
IF 4.6 Q1 OPHTHALMOLOGY Pub Date : 2025-11-11 DOI: 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.
目的:知觉学习是一种治疗弱视的新方法。本研究评估了延长PL持续时间是否能在弱视治疗中产生持续的治疗效果。设计:回顾性观察设计。方法对100例完成6个月侧掩术的患者中的93例进行分析,随访3或6个月。缺失数据的处理采用链式方程的多次插值。视觉功能的纵向变化——包括最佳矫正视力(BCVA)、对比敏感度函数(CSF)和立体视——使用线性混合效应模型进行评估。为了确定BCVA和脑脊液下面积(AULCSF)改善的相关因素,我们构建了多变量线性回归模型,纳入根据临床意义和现有文献证据选择的所有相关协变量。在BCVA和AULCSF分析中,每位患者仅纳入1只弱视眼。在双侧弱视的情况下,选择较差的眼睛进行初步分析。敏感性分析以两种方式进行:(1)使用更好的眼睛的测量值;(2)使用根据逻辑规则输入缺失值的数据集;将缺失值替换为剩余时间点的2个观测值的较差结果。主要结果测量包括BCVA、CSF和立体视敏度。结果共纳入受试者93例(男46例,女47例),平均年龄15.3±8.3岁。弱视亚型包括:等屈光(n = 8)、异屈光(n = 63)、斜视(n = 12)、剥夺性(n = 1)和混合性(n = 9)。分析显示BCVA和AULCSF均有显著且持续的改善。近立体视觉在3个月的PL训练后也得到了改善。然而,进一步延长训练时间并没有导致立体视觉的额外显著收益。多变量线性回归分析显示,初始基线视觉功能和闭塞治疗史是影响BCVA和AULCSF改善的主要因素。结论知觉学习治疗可改善弱视患者的视功能。考虑到延长视觉训练的时间仍然会导致可测量的视觉改善,6个月的视觉训练似乎是必要的。作者在本文中讨论的任何材料中没有专有或商业利益。
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Ophthalmology science
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