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Participants with age-related macular degeneration (AMD) and controls from the MACUSTAR study underwent functional testing, including mesopic fundus-controlled perimetry, best-corrected visual acuity, low-luminance visual acuity, low-luminance deficit, Moorfields Acuity Test, and Pelli-Robson contrast sensitivity, along with spectral-domain optical coherence tomography imaging. Structural and functional data were analyzed globally and spatially aligned for topographic analysis. Linear-mixed effects models, adjusted for age, sex, and eccentricity of the rEZR, assessed associations between rEZR and functional metrics. A total of 275 eyes (early AMD, n\u2009=\u200934; intermediate AMD, n\u2009=\u2009152; late AMD, n\u2009=\u200936; controls, n\u2009=\u200953) from 275 participants (mean\u2009\u00b1\u2009standard deviation age: 71.1\u2009\u00b1\u20097.2\u00a0years; 63.3% female) were included. In global analyses, rEZR was associated with the mean average threshold in mesopic fundus-controlled perimetry (coefficient estimate 0.0492, 95% confidence interval 0.0190\u20130.0794, p\u2009=\u20090.0015), low-luminance visual acuity (coefficient estimate \u2212\u00a00.0015, 95% confidence interval \u2212\u00a00.0026 to \u2212\u00a00.0004, p\u2009=\u20090.0092), Moorfields Acuity Test (coefficient estimate 0.0092, 95% confidence interval \u2212\u00a00.0022 to \u2212\u00a00.0001, p\u2009=\u20090.0285), and Pelli-Robson contrast sensitivity (coefficient estimate 0.0030, 95% confidence interval 0.0015\u20130.0045, p\u2009=\u20090.0001). Topographic analysis further revealed an association of rEZR with mesopic retinal sensitivity (coefficient estimate 0.0065, 95% confidence interval 0.0026\u20130.0104, p\u2009&lt;\u20090.0001). Higher outer retinal reflectivity is linked to better retinal function in AMD and controls, supporting its potential as a biomarker for retinal integrity and function.<\/jats:p>","DOI":"10.1038\/s41598-025-00735-7","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:57:20Z","timestamp":1750409840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report"],"prefix":"10.1038","volume":"15","author":[{"given":"Yannick N.","family":"Liermann","sequence":"first","affiliation":[]},{"given":"Charlotte","family":"Behning","sequence":"additional","affiliation":[]},{"given":"Ben","family":"Isselmann","sequence":"additional","affiliation":[]},{"given":"Matthias","family":"Schmid","sequence":"additional","affiliation":[]},{"given":"Hannah M. 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