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Participants were divided into fine-tuning (n=2,261) and analysis (n=6,070) cohorts based on their visit status across the two periods. The fine-tuning cohort only included individuals without a history of systemic or cardiovascular diseases. A deep learning model, originally released in the Japan Ocular Imaging Registry, was fine-tuned using a fine-tuning cohort to predict retinal age from images. This refined model was then applied to the analysis cohort to calculate retinal age gaps. We conducted cross-sectional and longitudinal analyses to examine the association of these gaps with systemic and cardiovascular diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The retinal age-prediction model achieved a mean absolute error of 3.00\u20133.42 years. Cross-sectional analysis revealed significant associations between the retinal age gap and a history of diabetes (\u03b2 = 1.08, p &lt; 0.001) and hyperlipidemia (\u03b2 = \u20130.67, p &lt; 0.001). Longitudinal analysis showed no significant association between the baseline retinal age gap and disease onset. However, onset of hypertension (\u03b2 = 0.35, p = 0.049) and hyperlipidemia (\u03b2 = 0.34, p = 0.035) showed marginal associations with an increase in retinal age gap over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The retinal age gap is a promising biomarker for systemic health, particularly in relation to diabetes, hypertension, and hyperlipidemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10384-025-01205-3","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T23:24:35Z","timestamp":1745969075000},"page":"616-623","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Association between the retinal age gap and systemic diseases in the Japanese population: the Nagahama study"],"prefix":"10.1007","volume":"69","author":[{"given":"Takuro","family":"Kamei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-3764","authenticated-orcid":false,"given":"Masahiro","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keina","family":"Sado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Morino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuharu","family":"Tabara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitaka","family":"Tsujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"1205_CR1","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1212\/WNL.0b013e318270401d","volume":"23","author":"BM Kissela","year":"2012","unstructured":"Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, et al. 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Kamei, None; M. Miyake, Grants or Contracts (Novartis), Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Bayer, Kowa, Alcon, HOYA, Novartis, AMO, Santen, Senju, Johnson & Johnson); K. Sado, None; K. Morino, None; Y. Mori, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Santen); Y. Tabara, None; F. Matsuda, None; H. Tamura, Grant (Findex), Lecture fee, Non-financial support (Novartis), Non-financial support (Bayer, Santen); A. Tsujikawa, Grants or Contracts (Canon, Findex, Santen, Kowa, Pfizer, Senju, Wakamoto, Alcon, Novartis, Otsuka, Bayer, Nitten), Consulting fees (Senju, Bayer, Novartis, HOYA, Ellex, MSD, Allegan, Eisai, Daiichi-Sankyo, Chugai, KYOWA HAKKO BIO), Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Bayer, Senju, Novartis, Santen, Alcon, AbbVie, AMO, Kowa, Canon, Otsuka, Wakamoto, NIDEK).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}