{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:50:00Z","timestamp":1790787000360,"version":"4.1.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Projekt DEAL"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Graefes Arch Clin Exp Ophthalmol"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>In September 2015, the first and so far only medication for treatment of Leber\u2019s hereditary optic neuropathy (LHON) was approved in the EU. The drug in question is idebenone (\u00a9Raxone) and has been given to all newly diagnosed patients of the University Eye Hospital Tuebingen since the approval of the drug. The aim of the study was to find out whether regular administration of the drug led to an improvement in vision. We retrospectively examined 2 cohorts of consecutive patients with newly occurred visual impairment and LHON diagnosis: One with the initial diagnosis made from January 2010 until April 2014 and a second from October 2015 until January 2020.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Retrospective, observational cohort study. All electronic medical files of newly diagnosed and genetically confirmed LHON patients of the University Eye Hospital Tuebingen from January 2010 until April 2014 (cohort 1) and October 2015 until January 2020 (cohort 2) with at least 12 months of follow-up examinations have been analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Five patients were included in the first and 7 patients in the second cohort. Patients of cohort 1 received no medication; patients of cohort 2, a daily dose of 900 mg idebenone. The primary visual acuity (VA) ranged between 0.03 and 0.5 in cohort 1 and did not improve during the observation period (median 60 months, range 23\u201387 months). The patients of cohort 2 have been observed for a median of 23 months (range 12\u201335 m). The primary VA ranged from 0.01 to 0.16. A recovery in one or both eyes with a final VA from 0.8 to 1.0 was experienced in 3 out of 7 patients. All patients showing a recovery of VA carried the m.11778G&gt;A mutation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The observed improvement in the treated cohort may be considered as\u00a0a hint on the efficacy of idebenone in LHON. The time course of improvement suggests that idebenone should be given 1.5 years in newly diagnosed LHON cases.<\/jats:p>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00417-020-05045-4","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T10:03:18Z","timestamp":1608285798000},"page":"1009-1013","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Leber\u2019s hereditary optic neuropathy: course of disease in consideration of idebenone treatment and type of mutation"],"prefix":"10.1007","volume":"259","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5192-0347","authenticated-orcid":false,"given":"Felix","family":"Tonagel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Kelbsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"5045_CR1","doi-asserted-by":"publisher","first-page":"461","DOI":"10.5301\/ejo.5000055","volume":"22","author":"B Mascialino","year":"2012","unstructured":"Mascialino B, Leinonen M, Meier T (2012) Meta-analysis of the prevalence of Leber hereditary optic neuropathy mtDNA mutations in Europe. Eur J Ophthalmol 22:461\u2013465. https:\/\/doi.org\/10.5301\/ejo.5000055","journal-title":"Eur J Ophthalmol"},{"key":"5045_CR2","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1086\/346066","volume":"72","author":"P Yu-Wai-Man","year":"2003","unstructured":"Yu-Wai-Man P, Griffiths PG, Brown DT, Howell N, Turnbull DM, Chinnery PF (2003) The epidemiology of Leber hereditary optic neuropathy in the north east of England. Am J Hum Genet 72:333\u2013339. https:\/\/doi.org\/10.1086\/346066","journal-title":"Am J Hum Genet"},{"key":"5045_CR3","first-page":"10","volume":"12","author":"EM Stone","year":"1992","unstructured":"Stone EM, Newman NJ, Miller NR, Johns DR, Lott MT, Wallace DC (1992) Visual recovery in patients with Leber\u2019s hereditary optic neuropathy and the 11778 mutation. J Clin Neuroophthalmol 12:10\u201314","journal-title":"J Clin Neuroophthalmol"},{"key":"5045_CR4","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1093\/brain\/awr192","volume":"134","author":"NJ Newman","year":"2011","unstructured":"Newman NJ (2011) Treatment of Leber hereditary optic neuropathy. Brain 134:2447\u20132450. https:\/\/doi.org\/10.1093\/brain\/awr192","journal-title":"Brain"},{"key":"5045_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-017-0583-3","volume":"17","author":"Y Mashima","year":"2017","unstructured":"Mashima Y, Kigasawa K, Shinoda K, Wakakura M, Oguchi Y (2017) Visual prognosis better in eyes with less severe reduction of visual acuity one year after onset of Leber hereditary optic neuropathy caused by the 11,778 mutation. BMC Ophthalmol 17:192. https:\/\/doi.org\/10.1186\/s12886-017-0583-3","journal-title":"BMC Ophthalmol"},{"key":"5045_CR6","doi-asserted-by":"publisher","first-page":"e17963","DOI":"10.1371\/journal.pone.0017963","volume":"6","author":"RH Haefeli","year":"2011","unstructured":"Haefeli RH, Erb M, Gemperli AC, Robay D, Courdier Fruh I, Anklin C, Dallmann R, Gueven N (2011) NQO1-dependent redox cycling of idebenone: effects on cellular redox potential and energy levels. PLoS One 6:e17963. https:\/\/doi.org\/10.1371\/journal.pone.0017963","journal-title":"PLoS One"},{"key":"5045_CR7","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s00417-008-0926-0","volume":"247","author":"C Lange","year":"2009","unstructured":"Lange C, Feltgen N, Junker B, Schulze-Bonsel K, Bach M (2009) Resolving the clinical acuity categories \u201chand motion\u201d and \u201ccounting fingers\u201d using the Freiburg Visual Acuity Test (FrACT). Graefe\u2019s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 247:137\u2013142. https:\/\/doi.org\/10.1007\/s00417-008-0926-0","journal-title":"Graefe\u2019s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie"},{"key":"5045_CR8","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1093\/brain\/awr170","volume":"134","author":"T Klopstock","year":"2011","unstructured":"Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S, Bailie M, Atawan A, Chattopadhyay S, Schubert M, Garip A, Kernt M, Petraki D, Rummey C, Leinonen M, Metz G, Griffiths PG, Meier T, Chinnery PF (2011) A randomized placebo-controlled trial of idebenone in Leber\u2019s hereditary optic neuropathy. Brain 134:2677\u20132686. https:\/\/doi.org\/10.1093\/brain\/awr170","journal-title":"Brain"},{"key":"5045_CR9","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1097\/WNO.0000000000000570","volume":"37","author":"V Carelli","year":"2017","unstructured":"Carelli V, Carbonelli M, de Coo IF, Kawasaki A, Klopstock T, Lagreze WA, La Morgia C, Newman NJ, Orssaud C, Pott JWR, Sadun AA, van Everdingen J, Vignal-Clermont C, Votruba M, Yu-Wai-Man P, Barboni P (2017) International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy. J Neuro-ophthalmol 37:371\u2013381. https:\/\/doi.org\/10.1097\/WNO.0000000000000570","journal-title":"J Neuro-ophthalmol"},{"key":"5045_CR10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/WNO.0000000000000830","volume":"40","author":"Y Moon","year":"2020","unstructured":"Moon Y, Kim US, Han J, Ahn H, Lim HT (2020) Clinical and optic disc characteristics of patients showing visual recovery in leber hereditary optic neuropathy. J Neuro-ophthalmol 40:15\u201321. https:\/\/doi.org\/10.1097\/WNO.0000000000000830","journal-title":"J Neuro-ophthalmol"},{"key":"5045_CR11","doi-asserted-by":"publisher","unstructured":"Pemp B, Kircher K, Reitner A (2019) Visual function in chronic Leber\u2019s hereditary optic neuropathy during idebenone treatment initiated 5 to 50 years after onset. Graefe\u2019s archive for clinical and experimental ophthalmology 257:2751\u20132757. https:\/\/doi.org\/10.1007\/s00417-019-04444-6","DOI":"10.1007\/s00417-019-04444-6"}],"container-title":["Graefe's Archive for Clinical and Experimental Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-020-05045-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00417-020-05045-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-020-05045-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T14:09:39Z","timestamp":1617286179000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00417-020-05045-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["5045"],"URL":"https:\/\/doi.org\/10.1007\/s00417-020-05045-4","relation":{},"ISSN":["0721-832X","1435-702X"],"issn-type":[{"value":"0721-832X","type":"print"},{"value":"1435-702X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,18]]},"assertion":[{"value":"29 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (educational grants; participation in speakers\u2019 bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Helmut Wilhelm and Carina Kelbsch have received honorarium for educational lectures from Santhera, the company that introduced idebenone into the market.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the local ethics committee of the faculty of medicine of the Eberhardt-Karls-University Tuebingen and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Because of the length of the investigation period, current address data of the patients were not available to us. The ethics committee of the faculty of medicine of the Eberhardt-Karls-University Tuebingen expressly permitted carrying out the study without informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}