{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:06Z","timestamp":1785437886722,"version":"3.56.0"},"reference-count":94,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, typically causing substantial, often permanent, central vision loss in young adults. It manifests as a subacute optic neuropathy, frequently progressing sequentially in both eyes, due to selective degeneration of retinal ganglion cells (RGCs). The condition is primarily associated with three mitochondrial DNA (mtDNA) point mutations\u2014m.11778G&gt;A, m.14484T&gt;C, and m.3460G&gt;A\u2014located in complex I of the mitochondrial respiratory chain. These mutations impair oxidative phosphorylation, elevate reactive oxygen species (ROS), and trigger apoptosis of RGCs. Although historically considered untreatable, emerging therapies provide new prospects. Idebenone, a synthetic CoQ10 analog, is the first pharmacologic agent approved in Europe, demonstrating partial visual recovery in patients treated early by improving mitochondrial electron transport and reducing oxidative stress. Gene therapy using allotopic expression of\n                    <jats:italic toggle=\"yes\">ND4<\/jats:italic>\n                    via adeno-associated viral vectors (rAAV2\/2-ND4) has shown improvement in both eyes even after unilateral injection. Advanced gene-editing techniques, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), offer potential approaches for correcting heteroplasmic mutations. High-throughput genetic testing, including whole-genome sequencing and clinical exome analysis, enables precise identification of nuclear modifiers that influence LHON phenotypes, facilitating early diagnosis and intervention. Current clinical trials, including RESTORE and REFLECT, emphasize the importance of prompt treatment to optimize visual outcomes.\n                  <\/jats:p>","DOI":"10.4103\/ijo.ijo_1696_25","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:00:27Z","timestamp":1785434427000},"page":"1151-1161","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Systematic review of Leber\u2019s hereditary optic neuropathy \u2013 Clinical diagnosis, genetics overview and current concepts of treatment"],"prefix":"10.4103","volume":"74","author":[{"given":"Selvakumar","family":"Ambika","sequence":"first","affiliation":[{"name":"Department of Neuro-Ophthalmology, Medical Research Foundation, Chennai, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundaramurthy","family":"Srilekha","sequence":"additional","affiliation":[{"name":"SNONGC, Department of Genetics and Molecular Biology, Medical Research Foundation, Chennai, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"R1-20260730","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":"R2-20260730","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1097\/WNO.0000000000001564","article-title":"The impact of Leber hereditary optic neuropathy on the quality of life of patients and their relatives: A qualitative study","volume":"42","author":"Chen","year":"2022","journal-title":"J Neuroophthalmol"},{"key":"R3-20260730","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.preteyeres.2010.11.002","article-title":"Mitochondrial optic neuropathies \u2013 disease 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