{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T13:29:46Z","timestamp":1783776586892,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI\u00ae), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged\u00a0\u2265\u00a02\u00a0months in the United States, and is currently under Health Authority review in the EU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Subjects included patients with SMA aged 2\u00a0months\u201360\u00a0years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age\u2010appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD\u2010OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2\u20136\u00a0months depending on study and assessment. SD\u2010OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 245 patients receiving risdiplam were assessed. Comprehensive, high\u2010quality, ophthalmologic monitoring assessing retinal structure and visual function showed no retinal structural or functional changes. In the youngest patients, SD\u2010OCT findings of normal retinal maturation were observed. AEs involving eye disorders were not suggestive of risdiplam\u2010induced toxicity and resolved with ongoing treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Extensive ophthalmologic monitoring conducted in studies in patients with SMA confirmed that risdiplam does not induce ophthalmologic toxicity in pediatric or adult patients with SMA at the therapeutic dose. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51239","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T21:47:05Z","timestamp":1606254425000},"page":"54-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy"],"prefix":"10.1002","volume":"8","author":[{"given":"Robert C.","family":"Sergott","sequence":"first","affiliation":[{"name":"Department of Neuro\u2010Ophthalmology Wills Eye Hospital Philadelphia USA"},{"name":"Annesley EyeBrain Center Thomas Jefferson University Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia M.","family":"Amorelli","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Nemo Center Catholic University and Policlinico Gemelli Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Baranello","sequence":"additional","affiliation":[{"name":"The Dubowitz Neuromuscular Centre NIHR Great Ormond Street Hospital Biomedical Research Centre Great Ormond Street Institute of Child Health University College London &amp; Great Ormond Street Hospital Trust London UK"},{"name":"Developmental Neurology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Barreau","sequence":"additional","affiliation":[{"name":"Institute of Myology Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Beres","sequence":"additional","affiliation":[{"name":"Department of Neurology Department of Ophthalmology Stanford University Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kane","sequence":"additional","affiliation":[{"name":"Columbia University Medical Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-5365","authenticated-orcid":false,"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Nemo Center Catholic University and Policlinico Gemelli Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Orazi","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Nemo Center Catholic University and Policlinico Gemelli Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"SantaMaria","sequence":"additional","affiliation":[{"name":"Annesley EyeBrain Center Thomas Jefferson University Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Tremolada","sequence":"additional","affiliation":[{"name":"Neuro\u2010Ophthalmology Center Ophthalmology Department IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Santarsiero","sequence":"additional","affiliation":[{"name":"Neuro\u2010Ophthalmology Center Ophthalmology Department IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Waskowska","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology Medical University of Gda\u0144sk Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeko","family":"Yashiro","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology National Center for Global Health and Medicine (NCGM) Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Denk","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development Pharmaceutical Sciences Roche Innovation Center Basel, F. 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