Ophthalmology science最新文献

{"title":"Data-Driven Detection of Subclinical Keratoconus via Semi-Supervised Clustering of Multidimensional Corneal Biomarkers","authors":"Lynn Kandakji PhD ,&nbsp;Shafi Balal MBBS ,&nbsp;Aleksander Stupnicki iBSc ,&nbsp;Siyin Liu MBBS, PhD ,&nbsp;Marcello Leucci BOptom ,&nbsp;Dan Gore MD ,&nbsp;Bruce Allan MD ,&nbsp;Nikolas Pontikos PhD","doi":"10.1016/j.xops.2025.100998","DOIUrl":"10.1016/j.xops.2025.100998","url":null,"abstract":"<div><h3>Purpose</h3><div>To objectively identify subclinical keratoconus (SKC) from a large sample of healthy and keratoconus (KC) patients via a data-driven framework on corneal imaging data from an anterior-segment OCT (AS-OCT) device (MS-39, CSO Italia).</div></div><div><h3>Design</h3><div>A retrospective cohort study.</div></div><div><h3>Subjects</h3><div>At 2 sites within the Moorfields Eye Hospital network in London, United Kingdom, 25 816 corneal scans from 5005 patients, including 3605 with KC and 1400 healthy control patients, were acquired between 2020 and 2024.</div></div><div><h3>Methods</h3><div>Principal component analysis (PCA) followed by Gaussian mixture modeling (GMM) was applied to AS-OCT–derived data, including 20 KC indices and patient age, to identify SKC eyes, which were then statistically compared against healthy and KC eyes. Subclinical KC eyes were also validated against external systems including same-day Pentacam (Oculus Optikgeräte) scans, Belin-Ambrosio’s ABCD system, KC progression criteria determined by a panel of corneal specialists, and the Moorfields Corneal Cross-linking (CXL) Risk Calculator.</div></div><div><h3>Main Outcome Measures</h3><div>Detection of SKC and progression of these eyes to clinically diagnosable KC over time.</div></div><div><h3>Results</h3><div>The GMM identified 166 eyes from 161 patients with distinct structural differences between healthy and KC eyes. These eyes clustered in the morphometric transition zone in PCA space and were predominantly classified as ABCD stage 0. However, they demonstrated asymmetry with their fellow eye, higher predicted CXL risk at 1–4 years (<em>P</em> &lt; 0.001), and faster progression to KC (log-rank <em>P</em> &lt; 0.0001) compared with healthy eyes. Among SKC eyes with longitudinal data, 72.7% met Global Consensus criteria for progression.</div></div><div><h3>Conclusions</h3><div>Subclinical KC remains challenging to detect, and although classic staging such as ABCD retains clinical utility, it is insufficient for early disease detection. Principal component analysis followed by GMM classification on a multidimensional AS-OCT dataset identifies a distinct and high-risk SKC group. This semisupervised framework offers a complementary tool for early risk stratification and can be applied to new patients via projection into the learned PCA space and computation of KC probability. Threshold values corresponding to the 25th and 75th percentiles of KC probability for each parameter may serve as clinical context for flagging eyes when multiple features fall in the atypical range.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 100998"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Reticular Pseudodrusen on Clinical and Ocular Characteristics and Progression Rate of Geographic Atrophy in Japanese Patients","authors":"Naoko Ueda-Arakawa MD, PhD ,&nbsp;Yukiko Sato MD, PhD ,&nbsp;Masahiro Miyake MD, PhD ,&nbsp;Ayako Takahashi MD, PhD ,&nbsp;Yuki Mori MD, PhD ,&nbsp;Yasunori Miyara MD ,&nbsp;Chikako Hara MD, PhD ,&nbsp;Yoko Kitajima MD ,&nbsp;Ruka Maruko MD, PhD ,&nbsp;Moeko Kawai MD ,&nbsp;Masayuki Ohnaka MD, PhD ,&nbsp;Hideki Koizumi MD, PhD ,&nbsp;Maiko Maruyama-Inoue MD, PhD ,&nbsp;Yasuo Yanagi MD, PhD ,&nbsp;Tomohiro Iida MD, PhD ,&nbsp;Mineo Kondo MD, PhD ,&nbsp;Taiji Sakamoto MD, PhD ,&nbsp;Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.xops.2025.100984","DOIUrl":"10.1016/j.xops.2025.100984","url":null,"abstract":"<div><h3>Purpose</h3><div>To elucidate the impact of reticular pseudodrusen (RPD) on the clinical and ocular characteristics and progression rate of geographic atrophy (GA) in Japanese patients.</div></div><div><h3>Design</h3><div>A multicenter, retrospective, observational cohort study.</div></div><div><h3>Participants</h3><div>A total of 173 eyes from 173 Japanese patients (135 with conventional GA and 35 with pachychoroid GA) were included; 79 eyes with conventional GA were included in the follow-up group.</div></div><div><h3>Methods</h3><div>Reticular pseudodrusen status, GA type (conventional/pachychoroid), GA location (central/noncentral), GA pattern (unifocal/multifocal), subfoveal choroidal thickness (SFCT), and fellow-eye status were assessed using multimodal imaging. The GA progression rate was calculated in both mm²/year and mm/year (square root transformation [SQRT]) after semiautomatic measurement of the GA area on fundus autofluorescence images.</div></div><div><h3>Main Outcome Measures</h3><div>Clinical and ocular characteristics and progression rate of GA according to RPD status.</div></div><div><h3>Results</h3><div>Reticular pseudodrusen were observed in 42.4% (73 eyes) of the 173 study eyes, 54.1% of the eyes with conventional GA, and none of the eyes with pachychoroid GA. Among patients with conventional GA, those with RPD were significantly more female (56.2 vs. 30.6%, <em>P</em> = 0.003), had better visual acuity (0.31 vs. 0.50 in logarithm of the minimum angle of resolution, <em>P</em> = 0.03), a smaller SFCT (141.7 vs. 185.0 μm, <em>P</em> = 0.02), higher prevalence of noncentral (56.2 vs. 32.3%, <em>P</em> = 0.005) and multifocal GA (68.5 vs. 29.0%, <em>P</em> &lt; 0.001), and bilateral late age-related macular degeneration (AMD) (93.1 vs. 65.0%, <em>P</em> &lt; 0.0001) than those without RPD. The GA progression rate was significantly higher in eyes with RPD than in eyes without RPD (0.34 vs. 0.18 mm/year [SQRT], <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Reticular pseudodrusen are frequently observed in Japanese patients with conventional GA. Clinical and ocular characteristics differ according to the RPD status, similarly in White patients. Geographic atrophy in the presence of RPD progresses rapidly, at a rate comparable to that in White patients, and most patients with RPD exhibit bilateral late AMD. Given that RPD in eyes with GA constitutes a strong risk factor for both fast GA progression and bilateral late AMD, GA with RPD should be treated at an early stage prior to foveal involvement, even though GA in Asians has been reported to progress slowly.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 100984"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645982","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":"Results from a Phase I Extension Study of Ciliary Neurotrophic Factor in Patients with Macular Telangiectasia Type 2","authors":"Lawrence J. Singerman MD ,&nbsp;Jean-Pierre Hubschman MD ,&nbsp;Martin Friedlander MD, PhD ,&nbsp;Emily Y. Chew MD ,&nbsp;Catherine Egan PhD ,&nbsp;Muna Bitar PharmD ,&nbsp;Thomas M. Aaberg Jr. MD","doi":"10.1016/j.xops.2025.101009","DOIUrl":"10.1016/j.xops.2025.101009","url":null,"abstract":"<div><h3>Objective</h3><div>To primarily assess long-term safety and retinal imaging outcomes of NT-501 (revakinagene taroretcel-lwey), which releases ciliary neurotrophic factor into the vitreous over an extended time, for treating macular telangiectasia type 2 (MacTel).</div></div><div><h3>Design</h3><div>Phase I, nonrandomized, multicenter, open-label extension study.</div></div><div><h3>Participants</h3><div>Six participants with bilateral MacTel who completed the parent 60-month phase I study.</div></div><div><h3>Methods</h3><div>In the parent study, participants had NT-501 surgically implanted in the study eye. The eye with more advanced disease was determined to be the study eye. For the purposes of this extension study, the fellow eye provided untreated natural history data. The extension study included visits 72, 84, 96, and 108 months postimplantation.</div></div><div><h3>Main Outcome Measures</h3><div>Safety outcomes included adverse events (AEs), change from baseline in best-corrected visual acuity (BCVA), and the proportions of eyes with ≥10- or ≥15-letter loss in BCVA from baseline. Retinal imaging variables included change from baseline in ellipsoid zone (EZ) (inner segment/outer segment) area loss and proportion of study eyes with ≥35% increase from baseline in EZ area loss.</div></div><div><h3>Results</h3><div>All implants were retained through the final study visit. All ocular treatment-emergent AEs were mild to moderate; none resulted in study discontinuation. No study eyes had ≥15-letter loss in BCVA from baseline at any study visit. Similarly, no study eyes had ≥10-letter loss at months 72, 84, and 96; 1 study eye (17%) experienced it at month 108. The portion of study eyes with a ≥35% increase in EZ area loss from baseline was lower (range, 50%–60%) relative to fellow eyes (range, 75%–100%).</div></div><div><h3>Conclusions</h3><div>Over the 9-year follow-up period, NT-501 was well tolerated and safe. Further studies are ongoing to investigate the long-term efficacy of NT-501 for treating MacTel.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101009"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OCT-PRO: A Multimodal Model Integrating OCT and Clinical Traits to Predict Postoperative Outcomes in Cataract Patients","authors":"Lixue Liu MD, PhD ,&nbsp;Mingyuan Li MS ,&nbsp;Yuxuan Wu MD, PhD ,&nbsp;Zizheng Cao MD ,&nbsp;Yuanjun Shang MD ,&nbsp;Lanqin Zhao MS ,&nbsp;Zhenyu Wang MD ,&nbsp;Junwei Tan BM ,&nbsp;Yan Yuan BM ,&nbsp;Wenbin Huang MD, PhD ,&nbsp;Jinghui Wang PhD ,&nbsp;Jianqiao Li PhD ,&nbsp;Fabao Xu PhD ,&nbsp;Zhangkai Lian MD ,&nbsp;Jianyu Pang MS ,&nbsp;Fan Xu PhD ,&nbsp;Ningning Tang PhD ,&nbsp;Xingru He DrPH, MBA ,&nbsp;Yan Xu MD ,&nbsp;Kun Zeng MD, PhD ,&nbsp;Haotian Lin MD, PhD","doi":"10.1016/j.xops.2025.101013","DOIUrl":"10.1016/j.xops.2025.101013","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Multicenter prospective cohort study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Prediction error of postoperative BCVA (logarithm of the minimum angle of resolution [logMAR]) measured by MAE and RMSE.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;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, &lt;em&gt;P&lt;/em&gt; = 0.003) and metadata-only models (0.229 logMAR, &lt;em&gt;P&lt;/em&gt; &lt; 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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Financial Disclosure(s)&lt;/h3&gt;&lt;div&gt;The author has no/the authors have no proprietary or commercial interest in any materia","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101013"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Optic Nerve Crush on Lens-Induced Myopia in Mice","authors":"Xiang-Hua Tang PhD, MD,&nbsp;Zhi-Peng Lai PhD, MD,&nbsp;Sheng-Song Xu PhD, MD,&nbsp;Jin-Yi Xu PhD, MD,&nbsp;Xiao Wang MD,&nbsp;Xing-Yu Lei BMed,&nbsp;Zhou-Yue Li PhD, MD,&nbsp;Xiao Yang PhD, MD","doi":"10.1016/j.xops.2025.101015","DOIUrl":"10.1016/j.xops.2025.101015","url":null,"abstract":"<div><h3>Objective</h3><div>The underlying mechanism of refractive development—whether it is confined to the local eyeball or involves the central visual pathways—remains controversial. This study aimed to explore the effect of optic nerve crush (ONC) on refractive development and lens-induced myopia (LIM) in mice and its potential mechanism.</div></div><div><h3>Design</h3><div>Laboratory experimental study.</div></div><div><h3>Subjects</h3><div>Three-week-old C57BL/6 mice were used in this study. The animals were divided into the following experimental groups: ONC group versus sham surgery (SHAM) group; ONC combined with LIM (ONC-LIM) group versus SHAM combined with LIM (SHAM-LIM) group; LIM followed by ONC group verus LIM group versus plano lens group.</div></div><div><h3>Methods</h3><div>The refraction and ocular biological parameters were measured. Bulk RNA-sequencing analysis was performed on retinas from the ONC group and the SHAM group. Differential expression analysis between groups was conducted using edgeR. Differentially expressed genes were selected by trend analysis to investigate the expression trends over different refractive conditions after ONC. The Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction analysis, and gene set enrichment analysis were conducted, and quantitative reverse transcription polymerase chain reaction was applied for validation.</div></div><div><h3>Main Outcome Measures</h3><div>The axial length (AL).</div></div><div><h3>Results</h3><div>The results indicated that, after ONC, 50% of the mice showed a myopic shift and 25% showed a hyperopic shift, and the changes in AL were consistent with refraction. The ONC-LIM group failed to develop myopic shift or axial elongation, unlike the SHAM-LIM group, suggesting that optical defocus could not induce a myopic shift in mice after ONC. RNA-sequencing analysis revealed several pathways associated with post-ONC refractive status, including glutamatergic synapse, gonadotropin-releasing hormone signaling, and long-term depression.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that intact optic nerve is necessary for normal murine emmetropization and for the development of LIM. While local ocular mechanisms remain the established paradigm for refractive regulation, our experimental results indicate the potential involvement of CNS pathways in ocular growth regulation. Further studies are needed to elucidate the precise mechanisms and potential interplay between local and central regulatory systems.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101015"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Datasheet for Age-Related Eye Disease Study 2 on the Database of Genotypes and Phenotypes","authors":"Souvick Mukherjee PhD,&nbsp;Akanksha Nagarkar BS, BA,&nbsp;Minali Prasad BA,&nbsp;Elvira Agron MA,&nbsp;Claire Weber PhD,&nbsp;Emily Y. Chew MD,&nbsp;Tharindu De Silva PhD","doi":"10.1016/j.xops.2025.100953","DOIUrl":"10.1016/j.xops.2025.100953","url":null,"abstract":"<div><h3>Objective</h3><div>To provide a comprehensive summary of the controlled-access Age-Related Eye Disease Study 2 (AREDS2) data elements, encompassing phenotypic, imaging, dietary, genetic, and ancillary data.</div></div><div><h3>Design</h3><div>Dataset description of a multicenter, phase III, randomized clinical trial evaluating lutein + zeaxanthin, ω-3, or both long-chain polyunsaturated fatty acid supplementation in intermediate age-related macular degeneration (AMD). Secondary randomization was offered to all AREDS2 participants to evaluate varying levels of zinc and the potential for elimination of β-carotene, which increases the risk of lung cancer in smokers.</div></div><div><h3>Participants</h3><div>A total of 4203 participants aged 50–85 years with bilateral intermediate AMD (bilateral large drusen ≥125 μm) or intermediate AMD in one eye and advanced AMD in the other eye were enrolled at 82 clinical centers between 2006 and 2008.</div></div><div><h3>Methods</h3><div>Participants attended annual clinic visits, including eye examinations, visual acuity, slit lamp, intraocular pressure, and imaging that included stereoscopic 30° color fundus (fields 1–3) and fundus reflex images in all participants, while fundus autofluorescence images and spectral-domain OCT images were acquired in selected clinics. Telephone contacts at 3 and 6 months and annually thereafter collected adverse events and reinforced visit compliance.</div></div><div><h3>Main Outcome Measures</h3><div>Progression to advanced AMD (central geographic atrophy or neovascular AMD), incidence of cataract surgery, and loss of ≥15 letters (≥3 lines) of visual acuity from baseline.</div></div><div><h3>Results</h3><div>Controlled-access data are archived under the database of Genotypes and Phenotypes (dbGaP) website with the accession number phs002015.v2.p1. The data elements include main-study phenotype tables plus multiple ancillary-study tables with cardiovascular, cognitive, nutritional biochemistry, and genetic data. Additional data include dietary assessments, image gradings, visual acuity testing, and cataract surgery documentation. Blood or saliva from &gt;2000 participants was collected; exome-chip data from &gt;1800 and whole-genome sequencing from 1363 participants, including 488 who also participated in the original AREDS, are available under the International AMD Genomics Consortium and dbGaP.</div></div><div><h3>Conclusions</h3><div>The AREDS2 dataset’s rigorous interventional design, standardized longitudinal ophthalmic imaging gradings, comprehensive dietary and genetic information, and ancillary cardiovascular and cognitive assessments constitute an invaluable resource for elucidating AMD progression, informing nutritional strategies, and artificial intelligence–driven diagnostics.</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 100953"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694609","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":"Novel Genotype–Phenotype Correlations in CRB1-Retinopathies","authors":"Ana Catalina Rodriguez-Martinez MD ,&nbsp;Cécile Méjécase PhD ,&nbsp;Vijay K. Tailor-Hamblin PhD ,&nbsp;Bethany E. Higgins PhD ,&nbsp;Robert H. Henderson MD ,&nbsp;Mariya Moosajee PhD","doi":"10.1016/j.xops.2025.101010","DOIUrl":"10.1016/j.xops.2025.101010","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluates genotype–phenotype correlations in <em>CRB1</em>-retinopathies using standardized phenotypic classification and comprehensive analysis of Crumbs homolog 1 (CRB1)-A and CRB1-B involvement alongside in silico protein modeling analysis.</div></div><div><h3>Design</h3><div>Retrospective multicenter cohort study.</div></div><div><h3>Subjects</h3><div>A total of 389 patients with biallelic disease-causing <em>CRB1</em> variants from 50 international cohorts, including 73 patients from Moorfields Eye Hospital.</div></div><div><h3>Methods</h3><div>Phenotypes were reclassified using standardized diagnostic criteria. Genotype–phenotype correlations were assessed based on CRB1 isoform involvement and protein domain localization of variants, supported by in silico structural modeling.</div></div><div><h3>Main Outcome Measures</h3><div>Associations between <em>CRB1</em> variant location, isoform involvement, and clinical phenotypes including Leber congenital amaurosis/early onset severe retinal dystrophy (LCA/EOSRD), retinitis pigmentosa (RP), cone-rod dystrophy, and macular dystrophy (MD).</div></div><div><h3>Results</h3><div>All patients had variants affecting CRB1-A, with none exclusively affecting CRB1-B. Mutations specific to CRB1-A, sparing CRB1-B were associated with MD. Mutations in exons 6, 7, and 9 were associated to LCA/EOSRD and RP phenotypes, whereas exon 2 variants were linked to MD. Genotype–phenotype correlations included c.1841G&gt;T p.(Gly614Val) linked to LCA/EOSRD and variants exclusively involving exon 11 and 12. Similarly, the variants c.2506C&gt;A p.(Pro836Thr) and c.498_506del p.(Ile167_Gly169del) were linked to MD.</div></div><div><h3>Conclusions</h3><div>Crumbs homolog 1-A must be affected for disease manifestation, while sparing of CRB1-B leads to milder phenotypes. Novel genotype–phenotype correlations were found using standardized phenotypic classification. Understanding protein structure and isoform involvement is crucial for accurate diagnosis, prognosis, and the development of targeted therapies.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101010"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037482","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":"Extending Treatment Duration in Perceptual Learning for Amblyopia","authors":"Yusong Zhou MD ,&nbsp;Qingqing Ye MB ,&nbsp;Xuan Qiu MD, PhD ,&nbsp;Zixuan Xu MD,&nbsp;Yunsi He MD,&nbsp;Ying Yao MD,&nbsp;Yangfei Pang MD,&nbsp;Wentong Yu MD,&nbsp;Yudan Zhong MM,&nbsp;Qiuying Li MM,&nbsp;Lei Feng MB,&nbsp;Junpeng Yuan BS,&nbsp;Yun Wen MD, PhD,&nbsp;Zhonghao Wang MD,&nbsp;Jinrong Li MD, PhD","doi":"10.1016/j.xops.2025.101005","DOIUrl":"10.1016/j.xops.2025.101005","url":null,"abstract":"<div><h3>Purpose</h3><div>Perceptual learning (PL) is a novel therapeutic approach for the treatment of amblyopia. This study evaluated whether extending the duration of PL could yield sustained therapeutic benefits in amblyopia management.</div></div><div><h3>Design</h3><div>A retrospective observational design.</div></div><div><h3>Methods</h3><div>Analysis included 93 of 100 patients who completed 6-month lateral masking PL and had 3- or 6-month follow-up data. Missing data were handled using multiple imputation by chained equations. Longitudinal changes in visual function—including best-corrected visual acuity (BCVA), contrast sensitivity function (CSF), and stereopsis—were evaluated using a linear mixed-effects model. To identify factors associated with improvements in BCVA and area under the log CSF (AULCSF), multivariable linear regression models were constructed, incorporating all relevant covariates selected based on clinical significance and evidence from existing literature. Only 1 amblyopic eye per patient was included in the analysis of BCVA and AULCSF. In cases of bilateral amblyopia, the worse eye was selected for the primary analysis. Sensitivity analyses were conducted in 2 ways: (1) using measurements from the better eye and (2) using datasets in which missing values had been imputed based on logical rules; the missing value was replaced with the worse outcome of the 2 observed values from the remaining time points.</div></div><div><h3>Main Outcome Measures</h3><div>Measurements included BCVA, CSF, and stereoacuity.</div></div><div><h3>Results</h3><div>A total of 93 participants (46 males and 47 females) were enrolled, with a mean age of 15.3 ± 8.3 years. Amblyopia subtypes included: isoametropic (n = 8), anisometropic (n = 63), strabismic (n = 12), deprivation (n = 1), and mixed (n = 9). Analysis revealed significant and sustained improvements in both BCVA and the AULCSF. Near stereopsis also improved following 3 months of PL training. However, further extension of the training duration did not result in additional significant gains in stereopsis. Multivariable linear regression analysis indicated that initial baseline visual function and history of occlusion therapy were the primary factors associated with the improvement of BCVA and AULCSF.</div></div><div><h3>Conclusions</h3><div>Perceptual learning treatment can improve the visual function of amblyopia patients. Considering that extending the duration of PL still resulted in measurable visual improvements, a 6-month training of PL appears to be necessary.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 101005"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravitreal Gene Therapy with LX102-C01 in Neovascular Age-Related Macular Degeneration: A Phase I Dose-Escalation Study of 12-Month Safety and Efficacy Outcomes","authors":"Junran Sun ,&nbsp;Mengxi Shen ,&nbsp;Jieqiong Chen ,&nbsp;Yidong Wu ,&nbsp;Yanping Zhou ,&nbsp;Jingyang Feng ,&nbsp;Yuxuan Cheng ,&nbsp;Huixun Jia ,&nbsp;Xiaolu Yang ,&nbsp;YuanYuan Gong ,&nbsp;Yang Liu ,&nbsp;Hong Wang ,&nbsp;Ruikang K. Wang ,&nbsp;Philip J. Rosenfeld ,&nbsp;Tong Li ,&nbsp;Fenghua Wang ,&nbsp;Xiaodong Sun","doi":"10.1016/j.xops.2025.100970","DOIUrl":"10.1016/j.xops.2025.100970","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the safety, tolerability, and preliminary efficacy of a single intravitreal injection of LX102-C01 in eyes with neovascular age-related macular degeneration (nAMD) followed up to 52 weeks.</div></div><div><h3>Design</h3><div>Open-label, single-center, dose-escalation investigator-initiated trial (NCT05831007) with 2 cohorts (3E10 vector genome [vg] and 1E11 vg per eye).</div></div><div><h3>Subjects</h3><div>Eyes with choroidal neovascularization secondary to nAMD, subretinal or intraretinal fluid, and a history of &gt;2 anti-VEGF treatments in the past 6 months with a good response.</div></div><div><h3>Methods</h3><div>All patients received 1 injection of aflibercept 2 weeks before LX102-C01. Dose escalation started with 3E10 vg and increased to 1E11 vg per eye. Visual acuity, anatomy, and adverse events (AEs) were assessed. Macular choroidal thickness (CT) and vascularity were measured using a 6 × 6 mm scan on swept-source OCT angiography imaging.</div></div><div><h3>Main Outcome Measures</h3><div>The primary endpoint was AEs at 1 year. The secondary endpoints were best-corrected visual acuity (BCVA), central subfield thickness (CST), and incidence of rescue treatment. Exploratory endpoints included the macular hypoautofluorescent area, CT, and choroidal vascularity index (CVI).</div></div><div><h3>Results</h3><div>Six eyes of 6 patients were included. There were no LX102-C01–related nonocular AEs. All LX102-C01–related ocular AEs were mild, predominantly anterior inflammation. There was no evidence of vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis. Two eyes from 2 patients developed recurrent subretinal fluid or hemorrhages that did not meet rescue criteria and resolved spontaneously after 1 to 2 months. All patients were free of rescue anti-VEGF treatments till the latest visit. Compared to baseline, BCVA maintained and CST decreased up to 12 months in both cohorts. The area of hypo-autofluorescence remained stable in both groups. The mean choroidal thickness (MCT) decreased from 162.1 μm to 147.1 μm (<em>P</em> = 0.03), but the CVI measurement showed no significant change (<em>P</em> = 0.6) up to 12 months. Changes in the MCT and CVI showed no statistically significant differences compared with the control group receiving standard aflibercept treatment.</div></div><div><h3>Conclusions</h3><div>LX102-C01 showed a favorable safety profile and potential efficacy in this preliminary 52-week study, with no observed macular atrophy, suggesting short-term tolerability of gene therapy associated anti-VEGF expression.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"6 2","pages":"Article 100970"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884430","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":"Chronic Kidney Disease as a Risk Factor for Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Analyses","authors":"Yu Jer Hsiao ,&nbsp;Hengtong Li MSc ,&nbsp;Can Can Xue PhD ,&nbsp;Crystal Chun Yuen Chong ,&nbsp;Enwen Zhu PhD ,&nbsp;Qiang Yuan ,&nbsp;Marco Yu PhD ,&nbsp;Chui Ming Gemmy Cheung MD ,&nbsp;Qiao Fan PhD ,&nbsp;Charumathi Sabanayagam PhD ,&nbsp;Yih-Chung Tham PhD ,&nbsp;Ching-Yu Cheng MD, PhD","doi":"10.1016/j.xops.2025.101036","DOIUrl":"10.1016/j.xops.2025.101036","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD).</div></div><div><h3>Design</h3><div>Prospective cohort study and 2-sample Mendelian randomization (MR) analyses.</div></div><div><h3>Participants</h3><div>Data from 430 016 participants in the UK Biobank cohort and summary statistics from the largest publicly available genome-wide association studies on estimated glomerular filtration rate (eGFR) (n = 1 004 040) and advanced AMD (n = 33 976; 16 144 cases) were analyzed.</div></div><div><h3>Methods</h3><div>Cox regression models were used to assess the association between CKD and incident AMD, adjusting for demographic, lifestyle, and clinical covariates. For MR analyses, we used the random-effects inverse-variance weighted model as the primary model, supported by 5 additional MR models for sensitivity analyses. A causal relationship was considered significant if <em>P</em> &lt; 0.05 in the primary model and in ≥2 sensitivity models, with all MR models showing a consistent effect direction. Colocalization analysis was performed to further identify shared genetic loci linking CKD and AMD.</div></div><div><h3>Main Outcome Measures</h3><div>Causal associations between eGFR and advanced AMD.</div></div><div><h3>Results</h3><div>In the UK Biobank, baseline CKD was significantly associated with an increased risk of incident AMD (hazard ratio, 1.12; 95% confidence interval [CI], 1.01–1.25; <em>P</em> = 0.035) over a 10-year follow-up. Mendelian randomization analyses also demonstrated causality between lower eGFR and higher risk of advanced AMD (odds ratio, 2.03; 95% CI, 1.01–4.08; <em>P</em> = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, <em>P</em> = 2.29 x 10^-33 for AMD; <em>P</em> = 2.29 x 10^-13 for eGFR).</div></div><div><h3>Conclusions</h3><div>Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD.</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 101036"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037949","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}