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Within the European multicenter, cross-sectional MACUSTAR study, we have devised an automatic approach to determine the mean rEZR [arbitrary units, AU] at two independent visits in SD-OCT volume scans in study participants. Linear mixed-effects models were applied to analyze the association of AMD stage and AMD associated high-risk features including presence of pigmentary abnormalities, reticular pseudodrusen (RPD), volume of the retinal-pigment-epithelial\u2013drusenoid-complex (RPEDC) with the rEZR. Intra-class correlation coefficients (ICC) were determined for rEZR reliability analysis. Within the overall study cohort (301 participants), we could observe decreased rEZR values (coefficient estimate\u2009\u00b1\u2009standard error) of \u2212\u20098.05\u2009\u00b1\u20092.44 AU (p\u2009=\u20090.0011) in the intermediate and of \u2212\u200922.35\u2009\u00b1\u20093.28 AU (p\u2009&lt;\u20090.0001) in the late AMD group. RPD presence was significantly associated with the rEZR in iAMD eyes (\u2212\u20096.49\u2009\u00b1\u20093.14 AU; p\u2009=\u20090.0403), while there was a good ICC of 0.846 (95% confidence interval: 0.809; 0.876) in the overall study cohort. This study showed an association of rEZR with increasing disease severity and the presence of iAMD high-risk features. Further studies are necessary to evaluate the rEZR\u2019s value as a novel biomarker for AMD and disease progression.<\/jats:p>","DOI":"10.1038\/s41598-022-18875-5","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T10:05:52Z","timestamp":1662113152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Relative ellipsoid zone reflectivity and its association with disease severity in age-related macular degeneration: a MACUSTAR study report"],"prefix":"10.1038","volume":"12","author":[{"given":"Marlene","family":"Sa\u00dfmannshausen","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":"Robert P.","family":"Finger","sequence":"additional","affiliation":[]},{"given":"Frank G.","family":"Holz","sequence":"additional","affiliation":[]},{"given":"Steffen","family":"Schmitz-Valckenberg","sequence":"additional","affiliation":[]},{"given":"Maximilian","family":"Pfau","sequence":"additional","affiliation":[]},{"name":"MACUSTAR Consortium","sequence":"additional","affiliation":[]},{"given":"H.","family":"Agostini","sequence":"additional","affiliation":[]},{"given":"L.","family":"Altay","sequence":"additional","affiliation":[]},{"given":"R.","family":"Atia","sequence":"additional","affiliation":[]},{"given":"F.","family":"Bandello","sequence":"additional","affiliation":[]},{"given":"P. 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