{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:49:52Z","timestamp":1791420592555,"version":"4.3.3"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHR Oxford Biomedical Research Centre","award":["NIHR203311"],"award-info":[{"award-number":["NIHR203311"]}],"id":[{"id":"https:\/\/ror.org\/00k27zs44","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Manchester Biomedical Research Centre","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}]},{"name":"Wellcome Trust","award":["216593\/Z\/19\/Z,224643\/Z\/21\/Z"],"award-info":[{"award-number":["216593\/Z\/19\/Z,224643\/Z\/21\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Klin Monbl Augenheilkd"],"abstract":"<jats:p>ABSTRACT in English\n\nBackground\nFamilial exudative vitreoretinopathy (FEVR) is a group of inherited retinal diseases characterised by abnormal retinal angiogenesis and peripheral non-perfusion. While over 10 genes have been implicated in FEVR, genotype-phenotype correlations and their clinical significance are incompletely understood. Here we describe a retrospective cohort of FEVR patients and assess the impact of defined genetic variants on protein structure, disease severity, inter-ocular variability, as well as treatment choices and visual outcomes.\n\nMethods\nRetrospective cohort of 51 patients with FEVR across three UK paediatric retina centres. All data was obtained from routine clinical records. Standard FEVR staging system was used throughout. Identified genetic variants were checked against genomic databases (ClinVar, GnomAD, UniProt), and their structural impact was examined using in silico algorithms (MutationTaster and PolyPhen2) to determine the likelihood of pathogenicity.\n\nResults\n51 patients were included, with variants identified in FZD4 (n=16), LRP5 (n=13), TSPAN12 (n=11), KIF11 (n=6), NDP (n=4), and CTNNB1 (n=1). In silico analysis identified 11 variants not previously reported in FEVR, seven of which were classified as likely pathogenic. NDP variants were associated with the most severe and asymmetrical disease. Management included conservative monitoring (45 eyes), retinal laser photocoagulation (39 eyes), and surgical interventions (12 eyes), with the majority of patients achieving stable or improved visual acuity in all treatment groups.\n\nConclusion\nThis study demonstrates significant diversity among FEVR patients with regards to genetic variants, clinical presentation, and visual outcomes. Understanding genotype-phenotype correlations in FEVR may be crucial for developing novel treatment strategies.\nABSTRACT in German\nHintergrund\n Die famili\u00e4re exsudative Vitreoretinopathie (FEVR) ist eine Gruppe erblicher Netzhauterkrankungen, die durch eine abnorme retinale Angiogenese und eine periphere Minderperfusion gekennzeichnet ist. Obwohl mehr als 10 Gene mit FEVR in Verbindung gebracht wurden, sind Genotyp-Ph\u00e4notyp-Korrelationen und deren klinische Bedeutung nur unvollst\u00e4ndig verstanden. In dieser Arbeit beschreiben wir eine retrospektive Kohorte von FEVR-Patienten und untersuchen den Einfluss definierter genetischer Varianten auf die Proteinstruktur, den Krankheitsschweregrad, die interokul\u00e4re Variabilit\u00e4t sowie auf Behandlungsentscheidungen und visuelle Ergebnisse.\nMethoden\n Retrospektive Kohorte von 51 Patienten mit FEVR aus drei p\u00e4diatrischen Netzhautzentren im Vereinigten K\u00f6nigreich. Alle Daten wurden aus routinem\u00e4\u00dfigen klinischen Aufzeichnungen gewonnen. Durchgehend wurde das Standard-FEVR-Staging-System verwendet. Die identifizierten genetischen Varianten wurden mit genomischen Datenbanken (ClinVar, GnomAD, UniProt) abgeglichen, und ihre strukturelle Auswirkung wurde mittels In-silico-Algorithmen (MutationTaster und PolyPhen2) untersucht, um die Wahrscheinlichkeit einer Pathogenit\u00e4t zu bestimmen.\nErgebnisse\n Es wurden 51 Patienten eingeschlossen, wobei Varianten in FZD4 (n=16), LRP5 (n=13), TSPAN12 (n=11), KIF11 (n=6), NDP (n=4) und CTNNB1 (n=1) identifiziert wurden. Die In-silico-Analyse identifizierte 11 zuvor nicht im Zusammenhang mit FEVR beschriebene Varianten, von denen sieben als wahrscheinlich pathogen eingestuft wurden. NDP-Varianten waren mit der schwersten und asymmetrischsten Erkrankung assoziiert. Das Management umfasste konservative \u00dcberwachung (45 Augen), retinale Laserphotokoagulation (39 Augen) und chirurgische Eingriffe (12 Augen), wobei die Mehrheit der Patienten in allen Behandlungsgruppen eine stabile oder verbesserte Sehsch\u00e4rfe erreichte.\nSchlussfolgerung\n Diese Studie zeigt eine erhebliche Vielfalt unter FEVR-Patienten hinsichtlich genetischer Varianten, klinischer Pr\u00e4sentation und visueller Ergebnisse. Das Verst\u00e4ndnis der Genotyp-Ph\u00e4notyp-Korrelationen bei FEVR k\u00f6nnte entscheidend f\u00fcr die Entwicklung neuartiger Behandlungsstrategien sein.<\/jats:p>","DOI":"10.1055\/a-2962-8394","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:09:51Z","timestamp":1791241791000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetics, management and clinical outcomes in familial exudative vitreoretinopathy (FEVR): a multicentre retrospective cohort"],"prefix":"10.1055","author":[{"given":"Tomasz","family":"Szeligowski","sequence":"first","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Oxford"],"department":["Oxford Eye Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Ie","sequence":"first","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Oxford"],"department":["Oxford Eye Hospital"]},{"name":"Great Ormond Street Hospital for Children, England, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kiraly","sequence":"first","affiliation":[{"name":"Manchester University NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Manchester"],"department":["Manchester Royal Eye Hospital"]},{"name":"University of Oxford Nuffield, England, United Kingdom of Great Britain and Northern Ireland","place":["Oxford"],"department":["Department of Clinical Neurosciences, Nuffield Laboratory of Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Hu","sequence":"additional","affiliation":[{"name":"University of Oxford Nuffield, England, United Kingdom of Great Britain and Northern Ireland","place":["Oxford"],"department":["Department of Clinical Neurosciences, Nuffield Laboratory of Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsveta","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Manchester University NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Manchester"],"department":["Manchester Royal Eye Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assad","family":"Jalil","sequence":"additional","affiliation":[{"name":"Manchester University NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Manchester"],"department":["Manchester Royal Eye Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Sergouniotis","sequence":"additional","affiliation":[{"name":"Manchester University NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Manchester"],"department":["Manchester Royal Eye Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Black","sequence":"additional","affiliation":[{"name":"Manchester University NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Manchester"],"department":["Manchester Centre for Genomic Medicine"]},{"name":"The University of Manchester School of Biological Sciences, England, United Kingdom of Great Britain and Northern Ireland","place":["Manchester"],"department":["Division of Evolution, Infection, and Genomics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui Chien","family":"Wong","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children, England, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan K.","family":"Patel","sequence":"additional","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Oxford"],"department":["Oxford Eye Hospital"]},{"name":"Great Ormond Street Hospital for Children, England, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Henderson","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children, England, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Ophthalmology"]},{"name":"Moorfields Eye Hospital NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Vitreoretinal surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0065-9131","authenticated-orcid":false,"given":"Kanmin","family":"Xue","sequence":"additional","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, England, United Kingdom of Great Britain and Northern Ireland","place":["Oxford"],"department":["Oxford Eye Hospital"]},{"name":"Great Ormond Street Hospital for Children, England, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Ophthalmology"]},{"name":"University of Oxford, England, United Kingdom of Great Britain and Northern Ireland","place":["Oxford"],"department":["Nuffield Laboratory of Ophthalmology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","container-title":["Klinische Monatsbl\u00e4tter f\u00fcr Augenheilkunde"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2962-8394.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:58:51Z","timestamp":1791417531000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2962-8394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1055\/a-2962-8394","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0023-2165","1439-3999"],"issn-type":[{"value":"0023-2165","type":"print"},{"value":"1439-3999","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10,5]]},"published":{"date-parts":[[2026,10,5]]}}}