{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:32:26Z","timestamp":1790271146918,"version":"4.1.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81901273"],"award-info":[{"award-number":["81901273"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Natural Science Foundation of Zhejiang Province","award":["ZCLY24H0903"],"award-info":[{"award-number":["ZCLY24H0903"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec015\">\n<jats:title>Background<\/jats:title>\n<jats:p>Biomarkers are widely recognized as crucial breakthroughs in tackling amyotrophic lateral sclerosis (ALS). Among them, retina markers may hold promise due to the close retina-brain connection and non-invasive, portable detection methods. Thus, using optical coherence tomography (OCT), we investigated the link between baseline cell-level retinal features and future ALS risk.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec016\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>Participants from the UK Biobank underwent OCT scans to assess retinal layers, macula, and optic disc parameters. Follow-up commenced two years after the baseline period (2006\u20132010), during which ALS cases were identified using International Classification of Diseases (ICD) codes from medical and assessment records. Cox proportional hazards models were applied to examine the relationship between retinal markers and incident ALS. Over a median follow-up of 14.11 years, 70 ALS cases occurred among 53,824 participants (incidence 10.58 per 100,000 person-years). Most participants were White (94.6%), 44.8% male, with a median age of 58 years. After adjusting for demographics and comorbidities affecting the retina, a standard deviation (SD) decrease of 15.19 \u00b5m in photoreceptor layer (PRL) thickness was associated with a 19% (95% confidence interval [7, 29]; <jats:italic>p<\/jats:italic>\u2009=\u20090.002) increased risk of ALS, while a SD increase of 26.11 \u00b5m in retinal pigment epithelium (RPE) thickness corresponded to a 20% (95% CI [7, 34]; <jats:italic>p<\/jats:italic>\u2009=\u20090.002) higher risk. Sensitivity analyses excluding follow-ups of less than 4 and 6 years yielded consistent results. Subgroup analyses showed these findings were more pronounced in smokers. The main limitation of this study is its single time point observational design.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec017\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>A thinner PRL and thicker RPE may precede the clinical diagnosis of ALS, offering potential clues for early diagnosis and insights into the disease\u2019s pathogenesis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004545","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T18:02:11Z","timestamp":1750874531000},"page":"e1004545","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of retinal markers and incident amyotrophic lateral sclerosis: An optical coherence tomography-based cohort study"],"prefix":"10.1371","volume":"22","author":[{"given":"Chunyang","family":"Pang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haobo","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6679-0864","authenticated-orcid":true,"given":"Dongsheng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4058-0738","authenticated-orcid":true,"given":"Binbin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"issue":"10360","key":"pmed.1004545.ref001","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic lateral sclerosis","volume":"400","author":"EL Feldman","year":"2022","journal-title":"Lancet"},{"issue":"3","key":"pmed.1004545.ref002","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S1474-4422(12)70014-5","article-title":"Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study","volume":"11","author":"S Byrne","year":"2012","journal-title":"Lancet Neurol"},{"key":"pmed.1004545.ref003","article-title":"Do the benefits of currently available treatments justify early diagnosis and treatment of amyotrophic lateral sclerosis? 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