Systemic comorbidities before and after onset in Leber hereditary optic neuropathy: a descriptive study

Introduction: lthough Leber hereditary optic neuropathy (LHON) is primarily an optic neuropathy, systemic comorbidities across the disease timeline have not been systematically described. We aimed to describe systemic comorbidities documented before and after LHON onset.Methods: We retrospectively reviewed medical records of 187 genetically confirmed patients with LHON (m.11778G>A, m.14484T>C, or m.3460G>A) seen at a single center between January 1990 and March 2025. Systemic comorbidities were extracted, standardized, coded into prespecified categories, and classified as present before onset or newly documented after onset. Findings were summarized as cumulative event counts and percentages; multiple events per patient were allowed.Results: The cohort comprised 156 males (83.4%) and had a median age at onset of 32.0 years. Before onset, 68 comorbidity events were recorded; alcohol-related, lifestyle-related, and gastrointestinal conditions were most frequent (12 events each). After onset, 27 newly documented events were recorded; mental health disorders were most frequent (nine events), followed by lifestyle-related conditions (five events).Discussion: Alcohol-related conditions were more commonly documented before onset, whereas mental health disorders were more commonly documented after onset. Early assessment of health behaviors and nutrition, and systematic attention to mental health after onset, may support comprehensive LHON care. These findings do not establish increased prevalence or causality.