Pub Date : 2026-02-01Epub Date: 2025-11-24DOI: 10.1016/j.xops.2025.101018
Jason Charng PhD , David Alonso-Caneiro PhD , Tina M. Lamey PhD , Jennifer A. Thompson PhD , Jeremiah K.H. Lim PhD , Elaine Ong MD , Terri L. McLaren BS , Fred K. Chen PhD, FRANZCO
Purpose
To compare microperimetry progression rate in USH2A-retinopathy using prespecified points based on fundus autofluorescence coregistration with loci preselected based on retinal sensitivity profile.
Design
Cohort longitudinal study.
Subjects
Seventeen eyes from 17 patients with biallelic pathogenic variants in USH2A gene.
Methods
Microperimetry was recorded using 10-2 grid. The grid was partitioned into 68 2° × 2° nonoverlapping squares, representing the retinal coverage of each locus. Four metrics were defined at baseline: (1) mean macular sensitivity (MMS): average sensitivity of all loci; (2) edge of scotoma sensitivity (ESS): average sensitivity of all loci adjacent to a scotomatous loci at baseline; (3) modified Rate of Progression in USH2A-related Retinal Degeneration study-defined functional transitional point (mFTP): selection based on ranking of the proportion peripheral adjacent loci that showed ≥7 decibel (dB) decrease; and (4) hyperautofluorescent ring sensitivity (HRS): average sensitivity of stimulus squares which the hyperautofluorescent ring boundary transects into. Trend-based progression rates (gradient from linear regression) were compared between these metrics, and event-based analysis of the US Food and Drug Administration-defined clinically significant change in visual field (mean change of ≥7 dB across ≥5 prespecified loci).
Main Outcome Measures
Trend- and event-based measures in MMS, ESS, mFTP, and HRS.
Results
Seventeen patients (median age 37.0 years) had mean baseline values of 9.7 dB, 9.2 dB, 17.9 dB, and 13.1 dB for MMS, ESS, mFTP, and HRS, respectively. Using all longitudinal data (mean follow-up 4.0 years), trend analysis showed mFTP progression rate (–1.53 ± 1.37 dB/year) was significantly faster than MMS (–0.51 ± 0.63 dB/year) and ESS (–1.11 ± 1.23 dB/year) but similar to HRS (–1.29 ± 1.41 dB/year). Edge of scotoma sensitivity was more prone to floor effect and had lower baseline sensitivity than mFTP and HRS. In event-based analysis, the proportion of eyes that demonstrated clinically significant mean change was similar between ESS (2-year 36.4%, overall 45.5%), mFTP (2-year 33.3%, overall 43.8%), and HRS (2-year 28.5%, overall 42.9%) but noticeable less in MMS (2-year 13.3%, overall 12.5%).
Conclusions
Hyperautofluorescent ring sensitivity and mFTP showed comparable performance in both trend- and event-based analyses, superior to that of MMS and ESS. Additional advantage of mFTP is inclusion of patients without the autofluorescent ring.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的比较基于眼底自身荧光共配的预先指定点与基于视网膜敏感性谱的预先选择位点在ush2a视网膜病变中的显微视野检查进展率。设计：队列纵向研究。研究对象：17例USH2A基因双等位致病变异患者的17只眼。方法采用10-2栅格法记录显微视野。网格被划分为68个2°× 2°不重叠的正方形，代表每个位点的视网膜覆盖范围。基线时定义了四个指标：(1)平均黄斑灵敏度（MMS）：所有位点的平均灵敏度；(2)暗点边缘灵敏度（edge of scotoma sensitivity， ESS）：暗点附近所有基因座在基线处的平均灵敏度；(3) ush2a相关视网膜变性研究定义的功能过渡点（mFTP）的改进进展率：根据显示≥7分贝（dB）下降的周围邻近基因座比例排序进行选择；(4)超自荧光环灵敏度（HRS）：超自荧光环边界横过的刺激方的平均灵敏度。基于趋势的进展率（线性回归的梯度）与美国食品和药物管理局定义的视野临床显著变化的基于事件的分析（≥5个预先指定的位点的平均变化≥7 dB）之间进行比较。主要结果测量MMS、ESS、mFTP和HRS中基于趋势和事件的测量。结果17例患者（中位年龄37.0岁）MMS、ESS、mFTP和HRS的平均基线值分别为9.7 dB、9.2 dB、17.9 dB和13.1 dB。使用所有纵向数据（平均随访4.0年），趋势分析显示mFTP进展率（-1.53±1.37 dB/年）显著快于MMS（-0.51±0.63 dB/年）和ESS（-1.11±1.23 dB/年），但与HRS相似（-1.29±1.41 dB/年）。暗点边缘敏感度较mFTP和HRS更易受地板效应影响，基线敏感度较低。在基于事件的分析中，在ESS（2年36.4%，总体45.5%）、mFTP（2年33.3%，总体43.8%）和HRS（2年28.5%，总体42.9%）中表现出临床显著平均变化的眼睛比例相似，但在MMS中明显较少（2年13.3%，总体12.5%）。结论shyperautofluorescence ring sensitivity和mFTP在基于趋势和事件的分析中表现相当，优于MMS和ESS。mFTP的另一个优点是包括没有自动荧光环的患者。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":"Anatomy- versus Sensitivity-Based Loci Preselection in Detecting USH2A-Retinopathy Microperimetric Progression","authors":"Jason Charng PhD , David Alonso-Caneiro PhD , Tina M. Lamey PhD , Jennifer A. Thompson PhD , Jeremiah K.H. Lim PhD , Elaine Ong MD , Terri L. McLaren BS , Fred K. Chen PhD, FRANZCO","doi":"10.1016/j.xops.2025.101018","DOIUrl":"10.1016/j.xops.2025.101018","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare microperimetry progression rate in <em>USH2A-</em>retinopathy using prespecified points based on fundus autofluorescence coregistration with loci preselected based on retinal sensitivity profile.</div></div><div><h3>Design</h3><div>Cohort longitudinal study.</div></div><div><h3>Subjects</h3><div>Seventeen eyes from 17 patients with biallelic pathogenic variants in <em>USH2A</em> gene.</div></div><div><h3>Methods</h3><div>Microperimetry was recorded using 10-2 grid. The grid was partitioned into 68 2° × 2° nonoverlapping squares, representing the retinal coverage of each locus. Four metrics were defined at baseline: (1) mean macular sensitivity (MMS): average sensitivity of all loci; (2) edge of scotoma sensitivity (ESS): average sensitivity of all loci adjacent to a scotomatous loci at baseline; (3) modified Rate of Progression in <em>USH2A</em>-related Retinal Degeneration study-defined functional transitional point (mFTP): selection based on ranking of the proportion peripheral adjacent loci that showed ≥7 decibel (dB) decrease; and (4) hyperautofluorescent ring sensitivity (HRS): average sensitivity of stimulus squares which the hyperautofluorescent ring boundary transects into. Trend-based progression rates (gradient from linear regression) were compared between these metrics, and event-based analysis of the US Food and Drug Administration-defined clinically significant change in visual field (mean change of ≥7 dB across ≥5 prespecified loci).</div></div><div><h3>Main Outcome Measures</h3><div>Trend- and event-based measures in MMS, ESS, mFTP, and HRS.</div></div><div><h3>Results</h3><div>Seventeen patients (median age 37.0 years) had mean baseline values of 9.7 dB, 9.2 dB, 17.9 dB, and 13.1 dB for MMS, ESS, mFTP, and HRS, respectively. Using all longitudinal data (mean follow-up 4.0 years), trend analysis showed mFTP progression rate (–1.53 ± 1.37 dB/year) was significantly faster than MMS (–0.51 ± 0.63 dB/year) and ESS (–1.11 ± 1.23 dB/year) but similar to HRS (–1.29 ± 1.41 dB/year). Edge of scotoma sensitivity was more prone to floor effect and had lower baseline sensitivity than mFTP and HRS. In event-based analysis, the proportion of eyes that demonstrated clinically significant mean change was similar between ESS (2-year 36.4%, overall 45.5%), mFTP (2-year 33.3%, overall 43.8%), and HRS (2-year 28.5%, overall 42.9%) but noticeable less in MMS (2-year 13.3%, overall 12.5%).</div></div><div><h3>Conclusions</h3><div>Hyperautofluorescent ring sensitivity and mFTP showed comparable performance in both trend- and event-based analyses, superior to that of MMS and ESS. Additional advantage of mFTP is inclusion of patients without the autofluorescent ring.</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 101018"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-10DOI: 10.1016/j.xops.2025.100976
Hemal P. Patel MD, Cason B. Robbins MD, Jamie J. Karl MD, Peter Weng MD, PhD, Lejla Vajzovic MD, FASRS, Sharon Fekrat MD, FASRS
{"title":"Corrigendum to “Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration” [Ophthalmology Science. 2025;5:100796]","authors":"Hemal P. Patel MD, Cason B. Robbins MD, Jamie J. Karl MD, Peter Weng MD, PhD, Lejla Vajzovic MD, FASRS, Sharon Fekrat MD, FASRS","doi":"10.1016/j.xops.2025.100976","DOIUrl":"10.1016/j.xops.2025.100976","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 100976"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-26DOI: 10.1016/j.xops.2025.101017
Christina Y. Weng MD, MBA, Kevin J. Blinder MD, Edward F. Hall MD, William N. Rosenthal MD
{"title":"Personalizing Personalized Medicine: The Pursuit of Optimal Thresholds in the Home OCT Artificial Intelligence Algorithm for Age-Related Macular Degeneration","authors":"Christina Y. Weng MD, MBA, Kevin J. Blinder MD, Edward F. Hall MD, William N. Rosenthal MD","doi":"10.1016/j.xops.2025.101017","DOIUrl":"10.1016/j.xops.2025.101017","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101017"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-04DOI: 10.1016/j.xops.2025.100993
Tenayaann Tresko BS, Shu Feng MD, Ethan Buhr PhD, Russell Van Gelder MD, PhD, Brian W. Chou MD, MA
Objective
Evaluate corneal sensitivity as a potential pathway for blue light–induced ocular discomfort.
Design
Cross-sectional study.
Subjects
Healthy adult volunteers without previous ocular medical history.
Methods
Subjects were exposed to a Hue A19 LED bulb calibrated for equivalent photo flux for 450 nm (blue) and 620 nm (red) wavelengths. Corneal sensitivity measurements via a 0.12-mm filament Cochet–Bonet esthesiometer were ascertained after 1 minute of exposure and throughout testing. The order of exposed wavelength was randomized, with a 5-minute rest interval between exposure to each wavelength of light.
Main Outcome Measures
Cochet–Bonnet measurements of (1) threshold to sensation, (2) discrimination, and (3) threshold to pain. Threshold to sensation was determined by the longest filament length at which the subject noted consistent initial sensation. Discrimination was determined by changing the filament length by 5-mm increments (both retraction and extension) until the subject was able to correctly and consistently distinguish less, greater, or equal sensation compared with the previous application. Threshold to pain was determined at the filament length at which the participant expressed pain or discomfort.
Results
There was no difference in threshold to sensation between blue (450 nm) and red (620 nm) light sources (P ≥ 0.99). There was no statistically significant difference in discrimination of stimuli under blue- or red-light exposure (P = 0.30), although blue-light exposure trended to be more sensitive. The threshold to pain under blue light was statistically significantly lower than in red-light conditions, with pain at a longer filament length under blue-light exposure compared with red-light exposure (median 12.5 mm vs. 7.5 mm, respectively; P = 0.03).
Conclusions
Blue- versus red-light exposure decreases subjective corneal pain threshold when measured by the Cochet–Bonnet esthesiometer. Altered corneal sensitivity may mediate blue light–induced ocular discomfort. The Cochet–Bonnet esthesiometer is a useful tool in the study of blue light–induced discomfort.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的探讨角膜敏感性作为蓝光致眼部不适的潜在途径。DesignCross-sectional研究。受试者：健康成人志愿者，无眼部病史。方法将受试者暴露于色相A19 LED灯泡下，校准450nm（蓝色）和620nm（红色）波长的等效光通量。在暴露1分钟和整个测试过程中，通过0.12 mm长丝Cochet-Bonet感受器测量角膜灵敏度。照射波长的顺序是随机的，每个波长的光照射之间有5分钟的休息间隔。主要结果测量cochet - bonnet测量(1)感觉阈值，(2)辨别阈值，(3)疼痛阈值。感觉阈值由受试者注意到一致初始感觉的最长灯丝长度决定。通过将灯丝长度以5毫米的增量（包括收缩和延长）改变来确定辨别，直到受试者能够正确和一致地区分与以前的应用相比更少、更大或相同的感觉。疼痛阈值是根据参与者表达疼痛或不适的纤维长度来确定的。结果蓝色光源（450 nm）与红色光源（620 nm）在感觉阈值上无显著差异（P≥0.99）。蓝光和红光对刺激的辨别差异无统计学意义（P = 0.30），但蓝光有更敏感的趋势。蓝光条件下的疼痛阈值比红光条件下的疼痛阈值有统计学意义上的显著降低，蓝光照射下的疼痛丝长度比红光照射下的疼痛丝长度更长（中位数分别为12.5 mm和7.5 mm, P = 0.03）。结论：与红光相比，蓝光照射可降低主观角膜痛觉阈值。角膜敏感性改变可能介导蓝光引起的眼部不适。Cochet-Bonnet感觉计是研究蓝光引起的不适的有用工具。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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Pub Date : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub Date: 2025-11-10DOI: 10.1016/j.xops.2025.100996
Yunyun Zou PhD , Jaeryung Kim MD, PhD , Taeun Kim MS , Soo-Eun Sung PhD , Jong Chul Han MD, PhD , Soon Cheol Cha MD, PhD , Do Young Park MD, PhD
Objective
To profile aqueous humor (AH)–derived exosomal microRNAs (miRNAs) in primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG) and investigate their potential as diagnostic biomarkers and modulators of extracellular matrix (ECM) remodeling in glaucoma pathogenesis.
Design
Prospective, comparative, observational pilot study.
Subjects and Controls
Aqueous humor was obtained from 21 patients with POAG, 24 patients with XFG, and 14 healthy donors.
Methods
Exosomes were isolated from pooled AH samples of patients with POAG, XFG, and healthy donors for small RNA sequencing. miR-29a, an ECM-targeting miRNA, was selected for functional validation in transforming growth factor-beta 2 (TGF-β2)– or dexamethasone (Dex)-induced collagen deposition models using human trabecular meshwork cells (HTMCs).
Main Outcome Measures
Identification of potential glaucoma- and subtype-specific exosomal miRNA biomarkers and evaluation of selected ECM-targeting miRNAs for their roles in modulating collagen expression in vitro.
Results
A total of 130 and 145 miRNAs were differentially expressed in POAG/Healthy and XFG/Healthy comparisons, respectively, with 96 miRNAs commonly dysregulated. Upregulation of ECM-related miRNAs—miR-21-5p, miR-92b-3p, miR-99a-5p, miR-486-3p, miR-486-5p, and miR-1260a—constituted a glaucoma-specific signature, whereas miR-99b-5p and miR-125a-5p showed subtype-specific upregulation in POAG, and miR-26a-5p and miR-451a in XFG. miR-29a-3p, a known antifibrotic miRNA, was significantly downregulated in POAG, XFG, and in HTMCs treated with TGF-β2 or Dex. Functional assays demonstrated that overexpression of miR-29a-3p attenuated TGF-β2- and Dex-induced collagen deposition in HTMCs.
Conclusions
This study provides the first profile of AH-derived exosomal miRNAs in POAG and XFG, identifies potential miRNAs associated with ECM remodeling, and highlights their potential utility as biomarkers and therapeutic targets in glaucoma.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的分析原发性开角型青光眼（POAG）和脱落型青光眼（XFG）中房水（AH）来源的外泌体microRNAs (miRNAs)，并探讨其作为青光眼发病机制中细胞外基质（ECM）重塑的诊断生物标志物和调节剂的潜力。前瞻性、比较性、观察性先导研究。从21例POAG患者、24例XFG患者和14例健康供者中获得幽默水。方法从POAG、XFG和健康供者的AH合并样本中分离性体，进行小RNA测序。miR-29a是一种靶向ecm的miRNA，我们选择它在转化生长因子-β2 (TGF-β2) -或地塞米松（Dex）诱导的胶原沉积模型中使用人小梁网细胞（HTMCs）进行功能验证。鉴定潜在的青光眼和亚型特异性外泌体miRNA生物标志物，并评估选定的ecm靶向miRNA在体外调节胶原表达中的作用。结果POAG/Healthy组和XFG/Healthy组分别有130和145个mirna差异表达，其中96个mirna普遍表达异常。ecm相关mirna - mir -21-5p、miR-92b-3p、miR-99a-5p、miR-486-3p、miR-486-5p和mir -1260a的上调构成青光眼特异性特征，而miR-99b-5p和miR-125a-5p在POAG中表现出亚型特异性上调，在XFG中表现出miR-26a-5p和miR-451a的上调。miR-29a-3p是一种已知的抗纤维化miRNA，在POAG、XFG和TGF-β2或Dex处理的htmc中显著下调。功能分析表明，过表达miR-29a-3p可减弱htmc中TGF-β2-和dex诱导的胶原沉积。本研究首次提供了POAG和XFG中ah来源的外显体mirna的图谱，鉴定了与ECM重塑相关的潜在mirna，并强调了它们作为青光眼生物标志物和治疗靶点的潜在用途。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":"A Pilot Study Profiling Aqueous Humor–Derived Exosomal MicroRNA in Primary Open-Angle and Exfoliation Glaucoma","authors":"Yunyun Zou PhD , Jaeryung Kim MD, PhD , Taeun Kim MS , Soo-Eun Sung PhD , Jong Chul Han MD, PhD , Soon Cheol Cha MD, PhD , Do Young Park MD, PhD","doi":"10.1016/j.xops.2025.100996","DOIUrl":"10.1016/j.xops.2025.100996","url":null,"abstract":"<div><h3>Objective</h3><div>To profile aqueous humor (AH)–derived exosomal microRNAs (miRNAs) in primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG) and investigate their potential as diagnostic biomarkers and modulators of extracellular matrix (ECM) remodeling in glaucoma pathogenesis.</div></div><div><h3>Design</h3><div>Prospective, comparative, observational pilot study.</div></div><div><h3>Subjects and Controls</h3><div>Aqueous humor was obtained from 21 patients with POAG, 24 patients with XFG, and 14 healthy donors.</div></div><div><h3>Methods</h3><div>Exosomes were isolated from pooled AH samples of patients with POAG, XFG, and healthy donors for small RNA sequencing. miR-29a, an ECM-targeting miRNA, was selected for functional validation in transforming growth factor-beta 2 (TGF-β2)– or dexamethasone (Dex)-induced collagen deposition models using human trabecular meshwork cells (HTMCs).</div></div><div><h3>Main Outcome Measures</h3><div>Identification of potential glaucoma- and subtype-specific exosomal miRNA biomarkers and evaluation of selected ECM-targeting miRNAs for their roles in modulating collagen expression in vitro.</div></div><div><h3>Results</h3><div>A total of 130 and 145 miRNAs were differentially expressed in POAG/Healthy and XFG/Healthy comparisons, respectively, with 96 miRNAs commonly dysregulated. Upregulation of ECM-related miRNAs—miR-21-5p, miR-92b-3p, miR-99a-5p, miR-486-3p, miR-486-5p, and miR-1260a—constituted a glaucoma-specific signature, whereas miR-99b-5p and miR-125a-5p showed subtype-specific upregulation in POAG, and miR-26a-5p and miR-451a in XFG. miR-29a-3p, a known antifibrotic miRNA, was significantly downregulated in POAG, XFG, and in HTMCs treated with TGF-β2 or Dex. Functional assays demonstrated that overexpression of miR-29a-3p attenuated TGF-β2- and Dex-induced collagen deposition in HTMCs.</div></div><div><h3>Conclusions</h3><div>This study provides the first profile of AH-derived exosomal miRNAs in POAG and XFG, identifies potential miRNAs associated with ECM remodeling, and highlights their potential utility as biomarkers and therapeutic targets in glaucoma.</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 100996"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-27DOI: 10.1016/j.xops.2025.100986
Alythia Vo BS , Liangbo Linus Shen MD , Irene Pak BS , Abu Tahir Taha BS , Antonio Z. Diaz BS , Jay M. Stewart MD
Objective
To investigate the relationship between baseline subfoveal choroidal thickness (SFChT) and both visual outcomes and geographic atrophy (GA) growth rate, and to assess whether SFChT mediates the treatment effect of oral metformin on GA progression.
Design
Secondary analysis of a randomized controlled trial.
Participants
Seventy eyes (34 metformin; 36 observation) from 44 participants (21 metformin; 23 observation) with GA and ≥6 months of follow-up in the METformin for the MINimization of Geographic Atrophy Progression study.
Methods
Subfoveal choroidal thickness was measured from baseline OCT. We calculated GA area growth rate by subtracting the GA area at the first visit from the GA area at the last visit and dividing the result by the time interval. Geographic atrophy perimeter-adjusted growth rate was calculated by dividing GA area growth rate by the mean GA perimeter between the first and last visit.
Main Outcome Measures
Longitudinal changes in GA area and visual acuity.
Results
Baseline SFChT was not significantly associated with baseline GA area (P = 0.51), baseline best-corrected visual acuity (BCVA) (P = 0.49), baseline low-luminance visual acuity (LLVA) (P = 0.85), or rim area focal hyperautofluorescence signals (P = 0.29). Baseline SFChT was not significantly associated with GA perimeter-adjusted growth rate (P = 0.74), the decline rate of BCVA (P = 0.14), and the decline rate of LLVA (P = 0.71). However, sensitivity analyses in GA subgroups found that baseline SFChT was associated with decreased rate of BCVA decline in patients with foveal-involving GA (Spearman ρ = 0.03, P = 0.03). Baseline SFChT did not significantly influence the effect of oral metformin on GA perimeter-adjusted growth rate (P = 0.78).
Conclusions
Greater baseline SFChT was significantly associated with slower BCVA decline in eyes with foveal-involving GA, suggesting a possible localized role of choroidal thickness in preserving central vision. However, SFChT was not associated with GA growth rate, LLVA decline, or baseline anatomical and functional measures. It also did not mediate the effect of oral metformin. While SFChT lacks prognostic value for GA progression overall, it may hold limited relevance for central vision outcomes in foveal-involving GA.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Association between Baseline Subfoveal Choroidal Thickness and Anatomical and Functional Outcomes in Geographic Atrophy","authors":"Alythia Vo BS , Liangbo Linus Shen MD , Irene Pak BS , Abu Tahir Taha BS , Antonio Z. Diaz BS , Jay M. Stewart MD","doi":"10.1016/j.xops.2025.100986","DOIUrl":"10.1016/j.xops.2025.100986","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between baseline subfoveal choroidal thickness (SFChT) and both visual outcomes and geographic atrophy (GA) growth rate, and to assess whether SFChT mediates the treatment effect of oral metformin on GA progression.</div></div><div><h3>Design</h3><div>Secondary analysis of a randomized controlled trial.</div></div><div><h3>Participants</h3><div>Seventy eyes (34 metformin; 36 observation) from 44 participants (21 metformin; 23 observation) with GA and ≥6 months of follow-up in the METformin for the MINimization of Geographic Atrophy Progression study.</div></div><div><h3>Methods</h3><div>Subfoveal choroidal thickness was measured from baseline OCT. We calculated GA area growth rate by subtracting the GA area at the first visit from the GA area at the last visit and dividing the result by the time interval. Geographic atrophy perimeter-adjusted growth rate was calculated by dividing GA area growth rate by the mean GA perimeter between the first and last visit.</div></div><div><h3>Main Outcome Measures</h3><div>Longitudinal changes in GA area and visual acuity.</div></div><div><h3>Results</h3><div>Baseline SFChT was not significantly associated with baseline GA area (<em>P</em> = 0.51), baseline best-corrected visual acuity (BCVA) (<em>P</em> = 0.49), baseline low-luminance visual acuity (LLVA) (<em>P</em> = 0.85), or rim area focal hyperautofluorescence signals (<em>P</em> = 0.29). Baseline SFChT was not significantly associated with GA perimeter-adjusted growth rate (<em>P</em> = 0.74), the decline rate of BCVA (<em>P</em> = 0.14), and the decline rate of LLVA (<em>P</em> = 0.71). However, sensitivity analyses in GA subgroups found that baseline SFChT was associated with decreased rate of BCVA decline in patients with foveal-involving GA (Spearman ρ = 0.03, <em>P</em> = 0.03). Baseline SFChT did not significantly influence the effect of oral metformin on GA perimeter-adjusted growth rate (<em>P</em> = 0.78).</div></div><div><h3>Conclusions</h3><div>Greater baseline SFChT was significantly associated with slower BCVA decline in eyes with foveal-involving GA, suggesting a possible localized role of choroidal thickness in preserving central vision. However, SFChT was not associated with GA growth rate, LLVA decline, or baseline anatomical and functional measures. It also did not mediate the effect of oral metformin. While SFChT lacks prognostic value for GA progression overall, it may hold limited relevance for central vision outcomes in foveal-involving GA.</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 100986"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-24DOI: 10.1016/j.xops.2025.101043
Zhen Ji Chen PhD , Jun Yu MMed , Mary Ho MSc , Danny S.C. Ng MPH , Marten E. Brelen PhD , Alvin L. Young MMedSc , Jason C.S. Yam MD , Clement C. Tham BM, BCh , Chi Pui Pang DPhil , Li Jia Chen PhD
<div><h3>Purpose</h3><div>To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H–complement factor H related 5 (<em>CFH</em>–<em>CFHR5</em>) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.</div></div><div><h3>Design</h3><div>Case-control genetic association study.</div></div><div><h3>Participants</h3><div>A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.</div></div><div><h3>Methods</h3><div>A total of 17 candidate SNPs were initially selected from the <em>CFH–CFHR5</em> region; after excluding 5 SNPs that deviated from Hardy–Weinberg equilibrium, 12 SNPs were retained for the final analysis. Association analyses included logistic regression adjusted for age and sex and haplotype-based analysis using Haploview. Study-wide significance threshold was set at <em>P</em> < 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at <em>P</em> < 0.05 for haplotype tests (adjusted using 10 000 permutations).</div></div><div><h3>Main Outcome Measures</h3><div>Associations between individual SNPs and haplotypes in the <em>CFH</em>–<em>CFHR5</em> locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.</div></div><div><h3>Results</h3><div>The tagging SNP, rs12144939, for the <em>CFHR3/1</em> deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, <em>P</em> = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, <em>P</em> = 6.29 × 10<sup>–4</sup>), rs423641 in <em>CFHR1</em> (OR = 0.74, <em>P</em> = 0.0038), and rs10922152 in <em>CFHR5</em> (OR = 1.55, <em>P</em> = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas <em>CFH</em> rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, <em>P</em> = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning <em>CFHR4</em>, <em>CFHR2,</em> and <em>CFHR5</em> (OR = 1.81, permutation <em>P</em> = 0.0099) and haplotype G-A-G within <em>CFHR5</em> (OR = 1.56, permutation <em>P</em> = 0.025) were specifically associated with PCV.</div></div><div><h3>Conclusions</h3><div>This study validates the association of the <em>CFHR3/1</em> deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the <em>CFH</em>–<em>CFHR5</em> locus, characterized by associations at rs12144939, rs423641 (<em>CFHR1</em>), and rs10922152 (<em>CFHR5</em>), as well as risk haplotypes unique to PCV. These findings underscore the critical role of <em>CFH</em>-related genes in PCV and provide new insights into its genetic mechanisms.</div></div><div><h3>Financial Disclosures</h3><div>The author h
{"title":"The CFH–CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy","authors":"Zhen Ji Chen PhD , Jun Yu MMed , Mary Ho MSc , Danny S.C. Ng MPH , Marten E. Brelen PhD , Alvin L. Young MMedSc , Jason C.S. Yam MD , Clement C. Tham BM, BCh , Chi Pui Pang DPhil , Li Jia Chen PhD","doi":"10.1016/j.xops.2025.101043","DOIUrl":"10.1016/j.xops.2025.101043","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H–complement factor H related 5 (<em>CFH</em>–<em>CFHR5</em>) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.</div></div><div><h3>Design</h3><div>Case-control genetic association study.</div></div><div><h3>Participants</h3><div>A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.</div></div><div><h3>Methods</h3><div>A total of 17 candidate SNPs were initially selected from the <em>CFH–CFHR5</em> region; after excluding 5 SNPs that deviated from Hardy–Weinberg equilibrium, 12 SNPs were retained for the final analysis. Association analyses included logistic regression adjusted for age and sex and haplotype-based analysis using Haploview. Study-wide significance threshold was set at <em>P</em> < 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at <em>P</em> < 0.05 for haplotype tests (adjusted using 10 000 permutations).</div></div><div><h3>Main Outcome Measures</h3><div>Associations between individual SNPs and haplotypes in the <em>CFH</em>–<em>CFHR5</em> locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.</div></div><div><h3>Results</h3><div>The tagging SNP, rs12144939, for the <em>CFHR3/1</em> deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, <em>P</em> = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, <em>P</em> = 6.29 × 10<sup>–4</sup>), rs423641 in <em>CFHR1</em> (OR = 0.74, <em>P</em> = 0.0038), and rs10922152 in <em>CFHR5</em> (OR = 1.55, <em>P</em> = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas <em>CFH</em> rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, <em>P</em> = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning <em>CFHR4</em>, <em>CFHR2,</em> and <em>CFHR5</em> (OR = 1.81, permutation <em>P</em> = 0.0099) and haplotype G-A-G within <em>CFHR5</em> (OR = 1.56, permutation <em>P</em> = 0.025) were specifically associated with PCV.</div></div><div><h3>Conclusions</h3><div>This study validates the association of the <em>CFHR3/1</em> deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the <em>CFH</em>–<em>CFHR5</em> locus, characterized by associations at rs12144939, rs423641 (<em>CFHR1</em>), and rs10922152 (<em>CFHR5</em>), as well as risk haplotypes unique to PCV. These findings underscore the critical role of <em>CFH</em>-related genes in PCV and provide new insights into its genetic mechanisms.</div></div><div><h3>Financial Disclosures</h3><div>The author h","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101043"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-08-06DOI: 10.1016/j.xops.2025.100907
Theodore Leng MD, MS , Ella H. Leung MD , S. Krishna Mukkamala MD , Mehran R. Taban MD , Moshe Havilio PhD , Kester Nahen PhD , Nishant Mohan PhD , Gidi Benyamini MBA , Tiarnan D.L. Keenan BM BCh, PhD
Purpose
Longitudinal validation of the artificial intelligence–based Notal OCT Analyzer (NOA) for identification of clinically significant changes in the trajectories of retinal total hypo-reflective volume (TRO) from daily home OCT (HOCT) self-imaging in eyes with age-related macular degeneration.
Design
Post hoc analysis of the HOCT Fluid Visualization Agreement Study.
Participants
Three hundred seventeen eyes of 180 participants who self-imaged daily using the HOCT for 5 weeks.
Methods
For each eye study, the ground truth of TRO stability or change was defined by human experts grading the 5-week time series of HOCT volume scans. The TRO trajectory of the 5 weeks was plotted separately for each study eye by NOA. Three approaches to identifying the optimal threshold (OT) for a clinically significant change in TRO were pursued: (1) personalized approach based on the reference change value methodology used in laboratory medicine; (2) optimized uniform approach; (3) uniform approach commonly used of 10 volume units (VU). The personalized approach comprised TRO curve-fitting to evaluate the change in amplitude (signal) and within-subject variations (noise), followed by receiver operating characteristic analysis of the signal-to-noise ratio (SNR) to identify the OT for determination of a clinically significant change in TRO.
Main Outcome Measures
Area under the receiver operating characteristic curve (AUROC); sensitivity, specificity, and accuracy at the OT.
Results
Of the 296 trajectories analyzed, 107 (36.1%) were classified as changing and the remaining 189 (63.9%) as stable. The personalized approach had an AUROC of 0.9811 (with 99.1% sensitivity, 89.4% specificity, and 94.2% accuracy), at OT of SNR = 2.42. The optimized uniform approach had an AUROC of 0.9687 (with 94.4% sensitivity, 89.4% specificity, and 91.9% accuracy), at OT of 3.88 VU. The 10 VU uniform approach had 76.6% sensitivity, 94.7% specificity, and 85.7% accuracy.
Conclusions
The NOA-generated trajectories permitted highly accurate determination of TRO change vs. stability, with favorable SNR. The personalized approach had higher sensitivity in detecting TRO change at 99.1% than the uniform approaches. Notal OCT analyzer and its trajectories were a reliable tool for identifying clinically relevant changes in retinal fluid status by the quality standards of laboratory medicine.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Longitudinal Validation of the Artificial Intelligence Algorithm in Home OCT for Age-Related Macular Degeneration—Report 3","authors":"Theodore Leng MD, MS , Ella H. Leung MD , S. Krishna Mukkamala MD , Mehran R. Taban MD , Moshe Havilio PhD , Kester Nahen PhD , Nishant Mohan PhD , Gidi Benyamini MBA , Tiarnan D.L. Keenan BM BCh, PhD","doi":"10.1016/j.xops.2025.100907","DOIUrl":"10.1016/j.xops.2025.100907","url":null,"abstract":"<div><h3>Purpose</h3><div>Longitudinal validation of the artificial intelligence–based Notal OCT Analyzer (NOA) for identification of clinically significant changes in the trajectories of retinal total hypo-reflective volume (TRO) from daily home OCT (HOCT) self-imaging in eyes with age-related macular degeneration.</div></div><div><h3>Design</h3><div>Post hoc analysis of the HOCT Fluid Visualization Agreement Study.</div></div><div><h3>Participants</h3><div>Three hundred seventeen eyes of 180 participants who self-imaged daily using the HOCT for 5 weeks.</div></div><div><h3>Methods</h3><div>For each eye study, the ground truth of TRO stability or change was defined by human experts grading the 5-week time series of HOCT volume scans. The TRO trajectory of the 5 weeks was plotted separately for each study eye by NOA. Three approaches to identifying the optimal threshold (OT) for a clinically significant change in TRO were pursued: (1) personalized approach based on the reference change value methodology used in laboratory medicine; (2) optimized uniform approach; (3) uniform approach commonly used of 10 volume units (VU). The personalized approach comprised TRO curve-fitting to evaluate the change in amplitude (signal) and within-subject variations (noise), followed by receiver operating characteristic analysis of the signal-to-noise ratio (SNR) to identify the OT for determination of a clinically significant change in TRO.</div></div><div><h3>Main Outcome Measures</h3><div>Area under the receiver operating characteristic curve (AUROC); sensitivity, specificity, and accuracy at the OT.</div></div><div><h3>Results</h3><div>Of the 296 trajectories analyzed, 107 (36.1%) were classified as changing and the remaining 189 (63.9%) as stable. The personalized approach had an AUROC of 0.9811 (with 99.1% sensitivity, 89.4% specificity, and 94.2% accuracy), at OT of SNR = 2.42. The optimized uniform approach had an AUROC of 0.9687 (with 94.4% sensitivity, 89.4% specificity, and 91.9% accuracy), at OT of 3.88 VU. The 10 VU uniform approach had 76.6% sensitivity, 94.7% specificity, and 85.7% accuracy.</div></div><div><h3>Conclusions</h3><div>The NOA-generated trajectories permitted highly accurate determination of TRO change vs. stability, with favorable SNR. The personalized approach had higher sensitivity in detecting TRO change at 99.1% than the uniform approaches. Notal OCT analyzer and its trajectories were a reliable tool for identifying clinically relevant changes in retinal fluid status by the quality standards of laboratory medicine.</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 100907"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925829","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}
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