{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:17:39Z","timestamp":1788200259388,"version":"build-2803163510"},"reference-count":18,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"crossref","award":["Open Fund Large collaborative Grant OFLCG23 May-0032"],"award-info":[{"award-number":["Open Fund Large collaborative Grant OFLCG23 May-0032"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Age-related macular degeneration (AMD) is a leading cause of vision impairment globally and demonstrates substantial variation regarding progression and clinical subtypes across populations. This paper describes the methodology of our study, designed to establish the natural history of AMD in Asian elderly and to identify predictors of progression from early signs of AMD to late AMD over a 5-year period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective, longitudinal cohort study aims to recruit 1500 participants from community-based cohorts in Singapore, with a follow-up duration of 5 years. Eligible participants are adults aged 55 years or older without severe systemic illness that would preclude participation.<\/jats:p>\n                    <jats:p>At baseline, demographic data and medical history will be collected, and visual acuity will be assessed. A basic imaging protocol including color fundus photography (CFP), optical coherence tomography (OCT), and OCT angiography (OCTA) will be performed. Blood samples will be collected from consenting participants. Images will be graded for early signs of AMD, defined as the presence of pathological findings on CFP, OCT, or OCTA.<\/jats:p>\n                    <jats:p>Participants without early signs of AMD will undergo annual follow-up using the basic imaging protocol. Those with any pathological findings at baseline or during follow-up will undergo an enhanced imaging protocol every 6 months, including ultrawide-field fundus photography, fundus autofluorescence (FAF), OCT, and OCTA. All follow-up visits will be conducted at the Singapore Eye Research Institute (SERI).<\/jats:p>\n                    <jats:p>Multimodal imaging biomarkers will be integrated with clinical, demographic, genetic, and metabolomic data to assess the relative risk of progression and identify potential predictors. The study protocol has been approved by the SingHealth Centralised Institutional Review Board.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>There is a paucity of data on the progression of AMD and optimal referral thresholds, particularly in Asian populations. This community-based cohort, representative of the general population, will generate one of the largest longitudinal datasets on AMD in Asia and aims to inform future screening strategies.<\/jats:p>\n                    <jats:p>\n                      Study registration number: ClinicalTrials.gov Identifier,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT07653269\" xlink:type=\"simple\">NCT07653269<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0355953","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T17:28:56Z","timestamp":1788197336000},"page":"e0355953","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting risk of progression of early to late AMD in the aging eye through imaging and multimodal evaluation: PRIME study protocol"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-4451","authenticated-orcid":true,"given":"Ali","family":"Forouhari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chui Ming Gemmy","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Low Lian","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Gilead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha","family":"Chakravarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7458-7081","authenticated-orcid":true,"given":"Kelvin Yi Chong","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"2","key":"pone.0355953.ref001","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis","volume":"2","author":"WL Wong","year":"2014","journal-title":"Lancet Glob Health"},{"issue":"6","key":"pone.0355953.ref002","first-page":"493","article-title":"Updates on the Epidemiology of Age-Related Macular Degeneration","volume":"6","author":"JB Jonas","year":"2017","journal-title":"Asia Pac J Ophthalmol (Phila)"},{"issue":"12","key":"pone.0355953.ref003","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-011504","article-title":"How does age-related macular degeneration affect real-world visual ability and quality of life? 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longitudinal cohort study from the University of Colorado AMD registry","volume":"10","author":"R Gnanaraj","year":"2025","journal-title":"BMJ Open Ophthalmol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355953","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T17:29:00Z","timestamp":1788197340000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355953"}},"subtitle":[],"editor":[{"given":"Alejandro","family":"Torrado 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