{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:43:12Z","timestamp":1792856592875,"version":"4.5.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The objective of the current study was to conduct an umbrella review of meta-analyses to systematically assess the methodological quality, potential biases, and validity of all epidemiological evidence addressing risk factors associated with age-related macular degeneration (AMD), and to synthesize the available evidence regarding AMD risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Web of Science, Embase, and the Cochrane Database of Systematic Reviews to April 2025 (last update) for systematic reviews and meta-analyses that focused on the risk factors for AMD. The methodological quality of each study was assessed independently by two reviewers using AMSTAR and the GRADE framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following a comprehensive systematic search, a total of 53 distinct risk factors were identified, comprising 30 factors with statistically significant associations and 23 without significant associations. Based on the GRADE framework, most of the evidence was classified as low or very low quality, with three factors achieving a moderate level of evidence. Consistent associations were observed for age and smoking, as well as for certain lifestyle and systemic factors, including diet, diabetes, and hypertension. Circulating biomarkers, including carotenoids, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL-C), were also found to be associated with AMD, although the strength of evidence varied across studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This umbrella review indicates that AMD risk is associated with multiple modifiable lifestyle and systemic factors. Healthy diet and physical activity may have protective roles, while several circulating biomarkers, including carotenoids and C-reactive protein, have been identified as related to AMD risk. However, given that most of the available evidence is of low or very low certainty, these findings should be considered with caution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      PROSPERO, CRD420251045558, URL:\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251045558<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1878292","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:48:35Z","timestamp":1781671715000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Risk factors for age-related macular degeneration: an umbrella analysis of systematic review and meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Huaixiao","family":"Zang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/S0140-6736(22)02609-5","article-title":"Age-related macular degeneration","volume":"401","author":"Guymer","year":"2023","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1001\/jama.2023.26074","article-title":"Age-related macular degeneration: a review","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"JAMA"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.ophtha.2012.10.036","article-title":"Clinical classification of age-related macular degeneration","volume":"120","author":"Ferris","year":"2013","journal-title":"Ophthalmology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of 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