{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T03:47:45Z","timestamp":1772682465181,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:00:00Z","timestamp":1696032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Leber\u2019s hereditary optic neuropathy (LHON) is a rare disease. Large studies are difficult to conduct; therefore, case reports provide valuable data. Since 2015, patients have been treated with Idebenone. The aim of this paper is to share our experience with diagnosing and managing patients in different stages of LHON. Methods: We designed a case series study, including four patients undergoing genetic testing and ophthalmologic examination. Criteria for Idebenone administration and follow-up were presented. Results: All patients had mutation 11778G&gt;A in MT-ND4. The first patient, an 82-year-old man, with long history of vision loss, had no indication for Idebenone. Two additional cases emerged within the same family: a 40-year-old brother and a 31-year-old sister. Both received Idebenone, with good outcomes only for the female. After a one-year regimen, they were lost to follow-up. The fourth patient, a 46-year-old man, was diagnosed in the subacute stage. Idebenone administration was deferred, allowing progression of visual field defects. After 17 months of treatment, visual improvement appeared. The treatment was continued for 36 months, with short interruptions, resulting in good outcomes. Conclusions: Our study demonstrated positive results with long-term Idebenone use. Contrary to medical literature, our female patient had a favorable evolution, despite the delayed diagnosis.<\/jats:p>","DOI":"10.3390\/life13102000","type":"journal-article","created":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T16:58:09Z","timestamp":1696179489000},"page":"2000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Leber\u2019s Hereditary Optic Neuropathy (LHON): Clinical Experience and Outcomes after Long-Term Idebenone Treatment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8261-1101","authenticated-orcid":false,"given":"George","family":"Balt\u0103","sequence":"first","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8032-5683","authenticated-orcid":false,"given":"Georgiana","family":"Cristache","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea Diana","family":"Barac","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-5049","authenticated-orcid":false,"given":"Nicoleta","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ileana Ramona","family":"Barac","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.5301\/ejo.5000055","article-title":"Meta-analysis of the prevalence of Leber hereditary optic neuropathy mtDNA mutations in Europe","volume":"22","author":"Mascialino","year":"2012","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_2","unstructured":"(2023, August 10). European Commission\u2014Health\u2014Rare Diseases. Available online: https:\/\/research-and-innovation.ec.europa.eu\/research-area\/health\/rare-diseases_en."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/BF01694557","article-title":"Ueber heredit\u00e4re und congenital-angelegte Sehnervenleiden","volume":"17","author":"Leber","year":"1871","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.3201231","article-title":"Mitochondrial DNA mutation associated with Leber\u2019s hereditary optic neuropathy","volume":"242","author":"Wallace","year":"1988","journal-title":"Science"},{"key":"ref_5","first-page":"77","article-title":"Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation","volume":"57","author":"Harding","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.jfo.2013.05.007","article-title":"Hereditary optic neuropathies: From clinical signs to diagnosis","volume":"36","author":"Meunier","year":"2013","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ajo.2022.11.004","article-title":"Visual Outcomes and Optical Coherence Tomography Biomarkers of Vision Improvement in Patients with Leber Hereditary Optic Neuropathy Treated With Idebenone","volume":"247","author":"Borrelli","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s11910-022-01246-y","article-title":"Developments in the Treatment of Leber Hereditary Optic Neuropathy","volume":"22","author":"Chen","year":"2022","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/sj.eye.6701591","article-title":"Hereditary optic neuropathies","volume":"18","author":"Newman","year":"2004","journal-title":"Eye"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2174\/138920211794520150","article-title":"LHON: Mitochondrial Mutations and More","volume":"12","author":"Kirches","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s40265-020-01428-3","article-title":"Therapeutic Options in Hereditary Optic Neuropathies","volume":"81","author":"Amore","year":"2021","journal-title":"Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.preteyeres.2003.10.003","article-title":"Mitochondrial dysfunction as a cause of optic neuropathies","volume":"23","author":"Carelli","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jha, R.K., Dawar, C., Hasan, Q., Pujar, A., Gupta, G., Vishnu, V.Y., and Thangaraj, K. (2021). Mitochondrial Genetic Heterogeneity in Leber\u2019s Hereditary Optic Neuropathy: Original Study with Meta-Analysis. Genes, 12.","DOI":"10.3390\/genes12091300"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shamsnajafabadi, H., MacLaren, R.E., and Cehajic-Kapetanovic, J. (2023). Current and Future Landscape in Genetic Therapies for Leber Hereditary Optic Neuropathy. Cells, 12.","DOI":"10.3390\/cells12152013"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1097\/WNO.0000000000001023","article-title":"Real-World Clinical Experience with Idebenone in the Treatment of Leber Hereditary Optic Neuropathy","volume":"40","author":"Catarino","year":"2020","journal-title":"J. Neuroophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.mito.2017.01.004","article-title":"Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy","volume":"36","author":"Soiferman","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1093\/brain\/awr170","article-title":"A randomized placebo-controlled trial of idebenone in Leber\u2019s hereditary optic neuropathy","volume":"134","author":"Klopstock","year":"2011","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e230","DOI":"10.1093\/brain\/aws279","article-title":"Persistence of the treatment effect of idebenone in Leber\u2019s hereditary optic neuropathy","volume":"136","author":"Klopstock","year":"2013","journal-title":"Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/WNO.0000000000000570","article-title":"International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy","volume":"37","author":"Carelli","year":"2017","journal-title":"J. Neuroophthalmol."},{"key":"ref_20","first-page":"433","article-title":"Long-term efficacy and safety of idebenone in patients with LHON in the subacute\/dynamic phase: Results from the LEROS study","volume":"63","author":"Klopstock","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1136\/jnnp-2014-308186","article-title":"MRI in Leber\u2019s hereditary optic neuropathy: The relationship to multiple sclerosis","volume":"86","author":"Matthews","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/1874364101206010065","article-title":"Optic neuritis, its differential diagnosis and management","volume":"6","author":"Hoorbakht","year":"2012","journal-title":"Open Ophthalmol. J."},{"key":"ref_23","first-page":"145","article-title":"Inherited mitochondrial optic neuropathies","volume":"46","author":"Griffiths","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pemp, B., Mitsch, C., Kircher, K., and Reitner, A. (2021). Changes in Visual Function and Correlations with Inner Retinal Structure in Acute and Chronic Leber\u2019s Hereditary Optic Neuropathy Patients after Treatment with Idebenone. J. Clin. Med., 10.","DOI":"10.3390\/jcm10010151"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1007\/s00417-019-04444-6","article-title":"Visual function in chronic Leber\u2019s hereditary optic neuropathy during idebenone treatment initiated 5 to 50 years after onset","volume":"257","author":"Pemp","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Parisi, V., Barbano, L., Di Renzo, A., Coppola, G., and Ziccardi, L. (2019). Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220435"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1097\/00041327-200020030-00006","article-title":"Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy?","volume":"20","author":"Mashima","year":"2000","journal-title":"J. Neuroophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e025307","DOI":"10.1136\/bmjopen-2018-025307","article-title":"What are the characteristics and progression of visual field defects in patients with Leber hereditary optic neuropathy: A prospective single-centre study in China","volume":"9","author":"Liu","year":"2019","journal-title":"BMJ Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/01658107.2022.2032761","article-title":"The Natural History of Leber\u2019s Hereditary Optic Neuropathy in an Irish Population and Assessment for Prognostic Biomarkers","volume":"2","author":"Stephenson","year":"2022","journal-title":"Neuroophthalmology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.tjo.2011.09.001","article-title":"Leber Hereditary Optic Neuropathy\u2014Therapeutic Challenges and Early Promise","volume":"1","author":"Chinnery","year":"2011","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.survophthal.2009.10.002","article-title":"The Neuro-ophthalmology of mitochondrial disease","volume":"55","author":"Fraser","year":"2010","journal-title":"Surv. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Spiegel, S.J., and Sadun, A.A. (2022). Solutions to a Radical Problem: Overview of Current and Future Treatment Strategies in Leber\u2019s Hereditary Opic Neuropathy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113205"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1097\/WNO.0000000000001045","article-title":"Visual Outcomes in Leber Hereditary Optic Neuropathy Patients with the m.11778G>A (MTND4) Mitochondrial DNA Mutation","volume":"40","author":"Newman","year":"2020","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Quigley, C., Stephenson, K.A.J., Kenna, P., and Cassidy, L. (2023). Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021068"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3109\/01658107.2016.1173709","article-title":"The Optical Coherence Tomographic Profile of Leber Hereditary Optic Neuropathy","volume":"2","author":"Hedges","year":"2016","journal-title":"Neuroophthalmology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13023-018-0936-x","article-title":"From scientific discovery to treatments for rare diseases\u2014The view from the National Center for Advancing Translational Sciences\u2014Office of Rare Diseases Research","volume":"13","author":"Kaufmann","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Benito-Lozano, J., Arias-Merino, G., G\u00f3mez-Mart\u00ednez, M., Ancochea-D\u00edaz, A., Aparicio-Garc\u00eda, A., Posada de la Paz, M., and Alonso-Ferreira, V. (2022). Diagnostic Process in Rare Diseases: Determinants Associated with Diagnostic Delay. Int. J. Environ. Res. Public Health, 26.","DOI":"10.3390\/ijerph19116456"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/10\/2000\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:03:09Z","timestamp":1760130189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/10\/2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,30]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["life13102000"],"URL":"https:\/\/doi.org\/10.3390\/life13102000","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,30]]}}}