A Comprehensive Review of Leber Hereditary Optic Neuropathy and Its Association with Multiple Sclerosis-Like Phenotypes Known as Harding’s Disease

Jehad Alorainy,1 Yara Alorfi,2 Rustum Karanjia,3– 5 Nooran Badeeb6 1College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia; 3Doheny Eye Centers, Department of Ophthalmology, David Geffen School of Medicine at UCLA, UCLA Stein Eye Institute, Los Angeles, CA, 90095-7000, USA; 4Ottawa Hospital Research Institute, the Ottawa Hospital, Ottawa, Canada; 5Doheny Eye Institute, Los Angeles, CA, USA; 6Department of Ophthalmology, University of Jeddah, Jeddah, Saudi ArabiaCorrespondence: Nooran Badeeb, Department of Ophthalmology, University of Jeddah, Jeddah, Saudi Arabia, Email nobadeeb@uj.edu.saAbstract: Leber Hereditary Optic Neuropathy (LHON) stands as a distinctive maternally inherited mitochondrial disorder marked by painless, subacute central vision loss, primarily affecting young males. This review covers the possible relationship between LHON and multiple sclerosis (MS), covering genetic mutations, clinical presentations, imaging findings, and treatment options. LHON is associated with mutations in mitochondrial DNA (mtDNA), notably m.11778G>A, m.3460G>A, and m.14484T>C, affecting complex I subunits. Beyond ocular manifestations, LHON can go beyond the eye into a multi-systemic disorder, showcasing extraocular abnormalities. Clinical presentations, varying in gender prevalence and outcomes, underscore the nature of mitochondrial optic neuropathies. Hypotheses exploring the connection between LHON and MS encompass mitochondrial DNA mutations triggering neurological diseases, immunologically mediated responses inducing demyelination, and the possibility of coincidental diseases. The research on mtDNA mutations among MS patients sheds light on potential associations with specific clinical subgroups, offering a unique perspective into the broader landscape of MS. Imaging findings, ranging from white matter alterations to cerebrospinal fluid biomarkers, further emphasize shared pathologi