Ophthalmology science最新文献

{"title":"Cover","authors":"","doi":"10.1016/j.xops.2026.101134","DOIUrl":"10.1016/j.xops.2026.101134","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 3","pages":"Article 101134"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147538914","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}

{"title":"Anatomy- versus Sensitivity-Based Loci Preselection in Detecting USH2A-Retinopathy Microperimetric Progression","authors":"Jason Charng PhD ,&nbsp;David Alonso-Caneiro PhD ,&nbsp;Tina M. Lamey PhD ,&nbsp;Jennifer A. Thompson PhD ,&nbsp;Jeremiah K.H. Lim PhD ,&nbsp;Elaine Ong MD ,&nbsp;Terri L. McLaren BS ,&nbsp;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}

{"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,&nbsp;Cason B. Robbins MD,&nbsp;Jamie J. Karl MD,&nbsp;Peter Weng MD, PhD,&nbsp;Lejla Vajzovic MD, FASRS,&nbsp;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}

{"title":"Cover","authors":"","doi":"10.1016/j.xops.2026.101091","DOIUrl":"10.1016/j.xops.2026.101091","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101091"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395340","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}

{"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,&nbsp;Kevin J. Blinder MD,&nbsp;Edward F. Hall MD,&nbsp;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}

{"title":"Effect of Light Wavelength on Corneal Sensitivity","authors":"Tenayaann Tresko BS,&nbsp;Shu Feng MD,&nbsp;Ethan Buhr PhD,&nbsp;Russell Van Gelder MD, PhD,&nbsp;Brian W. Chou MD, MA","doi":"10.1016/j.xops.2025.100993","DOIUrl":"10.1016/j.xops.2025.100993","url":null,"abstract":"<div><h3>Objective</h3><div>Evaluate corneal sensitivity as a potential pathway for blue light–induced ocular discomfort.</div></div><div><h3>Design</h3><div>Cross-sectional study.</div></div><div><h3>Subjects</h3><div>Healthy adult volunteers without previous ocular medical history.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Main Outcome Measures</h3><div>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.</div></div><div><h3>Results</h3><div>There was no difference in threshold to sensation between blue (450 nm) and red (620 nm) light sources (<em>P</em> ≥ 0.99). There was no statistically significant difference in discrimination of stimuli under blue- or red-light exposure (<em>P</em> = 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; <em>P</em> = 0.03).</div></div><div><h3>Conclusions</h3><div>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.</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 100993"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645994","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}

{"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":"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}

{"title":"A Pilot Study Profiling Aqueous Humor–Derived Exosomal MicroRNA in Primary Open-Angle and Exfoliation Glaucoma","authors":"Yunyun Zou PhD ,&nbsp;Jaeryung Kim MD, PhD ,&nbsp;Taeun Kim MS ,&nbsp;Soo-Eun Sung PhD ,&nbsp;Jong Chul Han MD, PhD ,&nbsp;Soon Cheol Cha MD, PhD ,&nbsp;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}

{"title":"Association between Baseline Subfoveal Choroidal Thickness and Anatomical and Functional Outcomes in Geographic Atrophy","authors":"Alythia Vo BS ,&nbsp;Liangbo Linus Shen MD ,&nbsp;Irene Pak BS ,&nbsp;Abu Tahir Taha BS ,&nbsp;Antonio Z. Diaz BS ,&nbsp;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}

{"title":"The CFH–CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy","authors":"Zhen Ji Chen PhD ,&nbsp;Jun Yu MMed ,&nbsp;Mary Ho MSc ,&nbsp;Danny S.C. Ng MPH ,&nbsp;Marten E. Brelen PhD ,&nbsp;Alvin L. Young MMedSc ,&nbsp;Jason C.S. Yam MD ,&nbsp;Clement C. Tham BM, BCh ,&nbsp;Chi Pui Pang DPhil ,&nbsp;Li Jia Chen PhD","doi":"10.1016/j.xops.2025.101043","DOIUrl":"10.1016/j.xops.2025.101043","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H–complement factor H related 5 (&lt;em&gt;CFH&lt;/em&gt;–&lt;em&gt;CFHR5&lt;/em&gt;) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Case-control genetic association study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A total of 17 candidate SNPs were initially selected from the &lt;em&gt;CFH–CFHR5&lt;/em&gt; 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 &lt;em&gt;P&lt;/em&gt; &lt; 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at &lt;em&gt;P&lt;/em&gt; &lt; 0.05 for haplotype tests (adjusted using 10 000 permutations).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Associations between individual SNPs and haplotypes in the &lt;em&gt;CFH&lt;/em&gt;–&lt;em&gt;CFHR5&lt;/em&gt; locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The tagging SNP, rs12144939, for the &lt;em&gt;CFHR3/1&lt;/em&gt; deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, &lt;em&gt;P&lt;/em&gt; = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, &lt;em&gt;P&lt;/em&gt; = 6.29 × 10&lt;sup&gt;–4&lt;/sup&gt;), rs423641 in &lt;em&gt;CFHR1&lt;/em&gt; (OR = 0.74, &lt;em&gt;P&lt;/em&gt; = 0.0038), and rs10922152 in &lt;em&gt;CFHR5&lt;/em&gt; (OR = 1.55, &lt;em&gt;P&lt;/em&gt; = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas &lt;em&gt;CFH&lt;/em&gt; rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, &lt;em&gt;P&lt;/em&gt; = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning &lt;em&gt;CFHR4&lt;/em&gt;, &lt;em&gt;CFHR2,&lt;/em&gt; and &lt;em&gt;CFHR5&lt;/em&gt; (OR = 1.81, permutation &lt;em&gt;P&lt;/em&gt; = 0.0099) and haplotype G-A-G within &lt;em&gt;CFHR5&lt;/em&gt; (OR = 1.56, permutation &lt;em&gt;P&lt;/em&gt; = 0.025) were specifically associated with PCV.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study validates the association of the &lt;em&gt;CFHR3/1&lt;/em&gt; deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the &lt;em&gt;CFH&lt;/em&gt;–&lt;em&gt;CFHR5&lt;/em&gt; locus, characterized by associations at rs12144939, rs423641 (&lt;em&gt;CFHR1&lt;/em&gt;), and rs10922152 (&lt;em&gt;CFHR5&lt;/em&gt;), as well as risk haplotypes unique to PCV. These findings underscore the critical role of &lt;em&gt;CFH&lt;/em&gt;-related genes in PCV and provide new insights into its genetic mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosures&lt;/h3&gt;&lt;div&gt;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}