Late-Onset Leber Hereditary Optic Neuropathy: A Case Series of 16 Patients Diagnosed Above 65 Years of Age

Leber hereditary optic neuropathy (LHON) is a mitochondrial optic neuropathy that typically affects young adult males. Late-onset disease is rare and often underrecognised. We conducted a retrospective case series of patients aged > 65 years at onset of visual loss diagnosed with LHON between 2004 and 2025 at two tertiary referral centers in Belgium and the Netherlands. Demographics, genetic mutations, environmental and systemic risk factors, visual outcomes, and response to idebenone were analyzed. Best-corrected visual acuity was assessed at presentation, nadir, and >1 year after onset. Treatment response was defined according to criteria for clinically relevant recovery. Sixteen male patients were included, with a mean age of onset of 72.8 years. The most frequent mutation was MT-ND4 (m.11778 G > A), followed by MT-ND6 (m.14484T > C) and MT-ND1 (m.4135T > C). Seven patients reported a family history, none had a symptomatic mother. Visual loss was severe at presentation in most cases. Twelve patients received idebenone therapy, with clinically relevant recovery observed in half. However, final visual acuity remained poor in the majority. Risk factors were common, including smoking, high-risk alcohol use, diabetes mellitus, and glaucoma. Late-onset LHON is a clinically relevant but underrecognised phenotype, likely reflecting interplay between genetic susceptibility, cumulative exposures, comorbidities, and age-related mitochondrial dysfunction. Increased awareness is needed for timely diagnosis and management in elderly patients with unexplained optic neuropathy.