{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:48:47Z","timestamp":1786618127718,"version":"build-2736575974"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271086"],"award-info":[{"award-number":["82271086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571275"],"award-info":[{"award-number":["82571275"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2026,5]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n To assess the prevalence and associations of the detectability of the three\u2010layer sign (TLS) in a general population, including individuals with age\u2010related macular degeneration (AMD) or without any retinal disease.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Using OCT images running horizontally through the foveola of participants of the population\u2010based Beijing Eye Study, we assessed the TLS detectability. We defined the TLS as the visibility of the ellipsoid zone (EZ), interdigitation zone and retinal pigment epithelium (RPE)\/Bruch's membrane line as separate units in the foveola on optical coherence tomographic (OCT) images.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study included 1566 eyes (age: 65.3\u2009\u00b1\u20099.8\u2009years; axial length: 23.01\u2009\u00b1\u20090.93\u2009mm; range: 19.90\u2009mm\u201028.93\u2009mm), randomly selected within each group of normal eyes (\n n<\/jats:italic>\n \u2009=\u2009592; 37.8%), eyes with early AMD (\n n<\/jats:italic>\n \u2009=\u2009700; 44.7%), intermediate AMD (\n n<\/jats:italic>\n \u2009=\u2009267; 17.0%), and late AMD (n\u2009=\u20097; 0.4%). In the normal group, TLS prevalence decreased with older age (OR: 0.93;\n p<\/jats:italic>\n \u2009<\u20090.001), declining from 217\/265 (81.9%) in the 50\u201359\u2009years age group to 57\/126 (45.2%) in individuals aged 70+ years. In the whole study cohort, TLS prevalence decreased (\n p<\/jats:italic>\n \u2009<\u20090.001) from 389\/592 (65.7%) in the normal group to 334\/700 (47.7%), 66\/267 (24.7%) and 0\/7 (0%) in early AMD, intermediate AMD and late AMD, respectively. In multivariable analysis, higher TLS prevalence was associated with younger age (OR: 0.92;\n p<\/jats:italic>\n \u2009<\u20090.001), female sex (OR: 1.65;\n p<\/jats:italic>\n \u2009<\u20090.001), lower AMD stage (OR: 0.51;\n p<\/jats:italic>\n \u2009<\u20090.001), better best\u2010corrected visual acuity (OR: 0.42;\n p<\/jats:italic>\n \u2009=\u20090.03), and lower prevalence of a flat retinal pigment epithelium elevation (OR: 0.68;\n p<\/jats:italic>\n \u2009=\u20090.04).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The foveal TLS may be taken as a qualitative sign of the intactness of the deep layers of the fovea, with its prevalence decreasing with older age, higher AMD stage and worse best\u2010corrected visual acuity.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/aos.70004","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:41:05Z","timestamp":1758282065000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prevalence and associations of the three\u2010layer sign in age\u2010related macular degeneration. The Beijing eye study"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2972-5227","authenticated-orcid":false,"given":"Jost B.","family":"Jonas","sequence":"first","affiliation":[{"name":"Rothschild Foundation Hospital Institut Fran\u00e7ais de Myopie Paris France"},{"name":"Singapore Eye Research Institute Singapore National Eye Center Singapore Singapore"},{"name":"Privatpraxis Prof Jonas und Dr. Panda\u2010Jonas Heidelberg Germany"},{"name":"Beijing Visual Science and Translational Eye Research Institute (BERI), Beijing Tsinghua Changgung Hospital, Tsinghua Medicine Tsinghua University Beijing China"},{"name":"L V Prasad Eye Institute Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhomitra","family":"Panda\u2010Jonas","sequence":"additional","affiliation":[{"name":"Privatpraxis Prof Jonas und Dr. Panda\u2010Jonas Heidelberg Germany"},{"name":"L V Prasad Eye Institute Hyderabad Telangana India"},{"name":"Department of Ophthalmology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Institute of Ophthalmology, Beijing Tongren Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-3047","authenticated-orcid":false,"given":"Rahul A.","family":"Jonas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Cologne University Hospital Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Visual Science and Translational Eye Research Institute (BERI), Beijing Tsinghua Changgung Hospital, Tsinghua Medicine Tsinghua University Beijing China"},{"name":"Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Institute of Ophthalmology, Beijing Tongren Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2022.11.026"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.12.034"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.10.34"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2020.09.018"},{"key":"e_1_2_8_6_1","first-page":"BIO211","article-title":"Activated retinal pigment epithelium, an optical coherence tomography biomarker for progression in age\u2010related macular degeneration","volume":"58","author":"Curcio C.A.","year":"2017","journal-title":"Investigative Ophthalmology & Visual 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