{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:13:29Z","timestamp":1787850809786,"version":"build-2784847793"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["MOH\u2010000655\u201000"],"award-info":[{"award-number":["MOH\u2010000655\u201000"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["MOH001014\u201000"],"award-info":[{"award-number":["MOH001014\u201000"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["05\/FY2020\/EX\/15\u2010A58"],"award-info":[{"award-number":["05\/FY2020\/EX\/15\u2010A58"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["05\/FY2022\/EX\/66\u2010A128"],"award-info":[{"award-number":["05\/FY2022\/EX\/66\u2010A128"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["Duke\u2010NUS\/RSF\/2021\/0018"],"award-info":[{"award-number":["Duke\u2010NUS\/RSF\/2021\/0018"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["A20H4g2141"],"award-info":[{"award-number":["A20H4g2141"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"publisher","award":["H20C6a0032"],"award-info":[{"award-number":["H20C6a0032"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To use artificial intelligence (AI) for quantifying schisis volume (ASV) in X\u2010linked retinoschisis (XLRS) for use as a structural endpoint in gene therapy clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used data from Singapore, the United Kingdom, the Netherlands, and the United States. The AI model was developed on 250 optical coherence tomography (OCT) slices, with human annotation of schisis cavities (Dataset 1). ASV was quantified on Dataset 2 \u2013 16 OCT scans from 8 eyes with XLRS at two time points, and Dataset 4 \u2013 62 OCT scans from 31 eyes at two time points before and after carbonic anhydrase inhibitor (CAI) treatment. A clinical trial was simulated comparing CAI treatment against control. Changes in ASV, central subfield thickness (CST) and central foveal thickness (CFT) were compared. Effect size (Cohen's\n                      <jats:italic>d<\/jats:italic>\n                      ) of the three structural endpoints was determined and used in sample size calculations for a future XLRS gene therapy clinical trial, at a 0.05 significance level and 80% power.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the simulated clinical trial, all structural metrics showed greater reductions with intervention than with control, but only change in ASV reached statistical significance (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004). Cohen's\n                      <jats:italic>d<\/jats:italic>\n                      for ASV, CST and CFT were 0.972, 0.685 and 0.521, respectively. For the future gene therapy clinical trial, sample sizes required in each arm for ASV, CST and CFT were 18, 35 and 59 participants, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ASV measurements can track changes in schisis volume in response to treatment. As an endpoint, ASV has a greater statistical effect size than CST\/CFT, which reduces sample size requirements for future XLRS gene therapy clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aos.17485","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T04:56:58Z","timestamp":1744693018000},"page":"715-724","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Artificial intelligence\u2010quantified schisis volume as a structural endpoint for gene therapy clinical trials in X\u2010linked retinoschisis"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9869-5159","authenticated-orcid":false,"given":"Tien\u2010En","family":"Tan","sequence":"first","affiliation":[{"name":"Singapore Eye Research Institute Singapore National Eye Centre  Singapore Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Programme (EYE ACP), Duke\u2010NUS Medical School  Singapore Singapore"},{"name":"Oxford Eye Hospital Oxford University Hospitals NHS Foundation Trust  Oxford UK"},{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1680-0526","authenticated-orcid":false,"given":"Peilun","family":"Dai","sequence":"additional","affiliation":[{"name":"Institute of High Performance Computing Agency for Science, Technology and Research (A*STAR)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2925-8940","authenticated-orcid":false,"given":"Jonathan","family":"Hensman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kiraly","sequence":"additional","affiliation":[{"name":"Oxford Eye Hospital Oxford University Hospitals NHS Foundation Trust  Oxford UK"},{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau J.","family":"Fenner","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute Singapore National Eye Centre  Singapore Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Programme (EYE ACP), Duke\u2010NUS Medical School  Singapore Singapore"},{"name":"The University of Iowa Institute for Vision Research The University of Iowa  Iowa City Iowa USA"},{"name":"Department of Ophthalmology and Visual Sciences, Carver College of Medicine The University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of High Performance Computing Agency for Science, Technology and Research (A*STAR)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick S. M.","family":"Goh","sequence":"additional","affiliation":[{"name":"Institute of High Performance Computing Agency for Science, Technology and Research (A*STAR)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"Han","sequence":"additional","affiliation":[{"name":"The University of Iowa Institute for Vision Research The University of Iowa  Iowa City Iowa USA"},{"name":"Department of Ophthalmology and Visual Sciences, Carver College of Medicine The University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S. W.","family":"Ting","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute Singapore National Eye Centre  Singapore Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Programme (EYE ACP), Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6737-7932","authenticated-orcid":false,"given":"Camiel J. F.","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Department of Ophthalmology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Dominik","family":"Fischer","sequence":"additional","affiliation":[{"name":"Oxford Eye Hospital Oxford University Hospitals NHS Foundation Trust  Oxford UK"},{"name":"Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"},{"name":"Centre for Ophthalmology University Hospital Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108344"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.13.9.18"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.05.025"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2012.05.001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1204095"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2021.09.021"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2018.09.006"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01520-9"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2023.12.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13185512"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.10.7.12"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","unstructured":"Karuntu J.S. Pfau M. Jolly J.K.&Boon C.J.F.(2024)Test\u2010retest variability of mesopic microperimetry\u2010associated parameters in patients with retinitis pigmentosa: REPEAT Study report No. 2. 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