{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:45:33Z","timestamp":1776253533954,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PharmaBio Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as an internal control in early-phase clinical trials for myopic CRA. Methods: This exploratory and methodological retrospective study included eight patients (16 eyes) with myopic CRA who visited the Department of Ophthalmology at Nagoya City University Hospital between January 2010 and August 2023. Atrophic areas in both eyes were measured, and the longitudinal changes were analyzed. Three mixed-effects models were compared to assess the impact of inter-individual and inter-ocular variability on atrophic area progression. Subsequently, fixed-effects and mixed-effects models were compared using the Akaike Information Criterion (AIC). Finally, the square root of the variance ratio was calculated to quantify the contribution of inter-ocular variability to atrophic area progression. Results: In all eyes, the square root of the atrophic area increased over time. The model including random intercepts and slopes for each eye nested within patients had the lowest AIC of 69.4, suggesting that accounting for both inter-individual and inter-ocular variability improved model accuracy. The mixed-effects model had a lower AIC than the fixed-effects model, indicating a better fit. The square root of the variance ratio was 0.34 in the mixed-effects model, indicating that the inter-ocular variability was lower than the inter-individual variability, though it remained appreciable. Conclusions: This study quantitatively supports the feasibility and methodological validity of inter-ocular comparison designs for early-phase clinical trials in myopic CRA.<\/jats:p>","DOI":"10.3390\/jcm15082997","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:30:23Z","timestamp":1776249023000},"page":"2997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the Validity of the Fellow Eye as an Internal Control in Early-Phase Clinical Trials for Myopic Chorioretinal Atrophy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-8546","authenticated-orcid":false,"given":"Norimichi","family":"Nagano","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eisaku","family":"Kanemori","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-0839","authenticated-orcid":false,"given":"Yoshio","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Hojo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukinori","family":"Sakaeda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Yuguchi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soichiro","family":"Kuwayama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuntaro","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayo","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Uemura","sequence":"additional","affiliation":[{"name":"Interfaculty Initiative in Information Studies, Graduate School of Interdisciplinary Information Studies, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9913-1905","authenticated-orcid":false,"given":"Tsutomu","family":"Yasukawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"ref_2","first-page":"82","article-title":"Geographic Atrophy in Age-Related Macular Degeneration","volume":"122","author":"Liakopoulos","year":"2025","journal-title":"Dtsch. 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