Updated Review of Leber Hereditary Optic Neuropathy

Purpose of Review: We aim to present a comprehensive review of Leber hereditary optic neuropathy (LHON), detailing currently established practices for diagnosis and management, as well as emerging research on novel therapies. Recent Findings: A randomized, placebo-controlled, double-masked trial demonstrated, in a post hoc analysis, that the anti-oxidant supplement idebenone may offer visual benefit in a subset of LHON patients early in the disease course. Several recent clinical trials have evaluated the safety and efficacy of gene therapy targeting the most common LHON mutation, m.11778/ND4. These trials unexpectedly reported bilateral visual improvement with monocular treatment, which prevented them from meeting their primary endpoints due to lack of the anticipated internal control (the untreated eye). However, when compared with previously published natural history studies, phase 3 clinical trials evaluating the gene therapy Lumevoq® (lenadogene nolparvovec) demonstrated sustained bilateral visual improvement, both with monocular and binocular treatment. Summary: Studies of gene therapy for LHON have shown modestly promising results, and more studies are planned. As of April 2022, no gene therapy agents have received marketing approval from the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). For now, multidisciplinary support, with idebenone in some cases, remains the standard management for LHON patients, offering a means for functionality despite vision loss.