{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:02:29Z","timestamp":1792828949320,"version":"4.5.0"},"reference-count":36,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leon Rosenberg, M.D. Medical Student Research Fund in Genetics at Yale School of Medicine","award":["no award\/grant number"],"award-info":[{"award-number":["no award\/grant number"]}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["no award\/grant number"],"award-info":[{"award-number":["no award\/grant number"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205174\/Z\/16\/Z"],"award-info":[{"award-number":["205174\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"All May See Foundation","award":["no award\/grant number"],"award-info":[{"award-number":["no award\/grant number"]}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30 EY002162"],"award-info":[{"award-number":["P30 EY002162"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Br J Ophthalmol"],"accepted":{"date-parts":[[2024,7,20]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To investigate the long-term natural history of ellipsoid zone (EZ) width in\n                      <jats:italic>USH2A<\/jats:italic>\n                      -retinopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      EZ width measurements from optical coherence tomography were retrospectively obtained from 110 eyes of 55 participants with molecularly confirmed biallelic\n                      <jats:italic>USH2A<\/jats:italic>\n                      -retinopathy. We used a hierarchical Bayesian method to construct and compare different mathematical models describing the long-term decline of EZ width.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with linear and quadratic models, exponential decline best represented the long-term loss of EZ width based on the deviance information criterion score. Log-transformed EZ width declined linearly over 30 years of inferred disease duration (median: 0.063 (IQR: 0.040\u20130.086) log (\u00b5m)\/year). Compared with the raw EZ width decline rate, the log-transformed EZ width decline rate required 48% fewer patients to achieve an identically powered 1-year trial (38 vs 73 participants). Log EZ width decline rate was uncoupled from baseline EZ width (Spearman \u03c1=\u22120.18, p=0.06) and age (\u03c1=\u22120.10, p=0.31). Eyes with Usher syndrome exhibited earlier median onset ages of macular EZ width loss (18.8 (IQR: 13.1\u201324.7) vs 28.1 (IQR: 18.5\u201335.8) years, p&lt;0.001) but comparable log EZ width decline rates (0.060 (IQR: 0.035\u20130.100) vs 0.065 (IQR: 0.050\u20130.079) log (\u00b5m)\/year; p=0.42).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      EZ width follows an exponential decline in\n                      <jats:italic>USH2A<\/jats:italic>\n                      -retinopathy. Compared with raw EZ width decline rate, log-transformed EZ width decline rate may be a superior endpoint for clinical trials. Syndromic eyes exhibit an earlier onset of macular EZ width loss but progress at comparable rates to non-syndromic eyes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bjo-2024-325323","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T13:28:28Z","timestamp":1722864508000},"page":"383-390","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Long-term natural history of ellipsoid zone width in\n                    <i>USH2A<\/i>\n                    -retinopathy"],"prefix":"10.1136","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5960-949X","authenticated-orcid":false,"given":"Michael","family":"Heyang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L","family":"Warren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Ocieczek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacque L","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian V","family":"Del Priore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-0854","authenticated-orcid":false,"given":"Liangbo Linus","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"2025040422451549000_109.3.383.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.03.005"},{"key":"2025040422451549000_109.3.383.2","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.108330","article-title":"USH2A-retinopathy: from genetics to therapeutics","volume":"201","author":"Toualbi","year":"2020","journal-title":"Exp Eye Res"},{"key":"2025040422451549000_109.3.383.3","doi-asserted-by":"crossref","unstructured":"Toms M , Pagarkar W , Moosajee M . 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