Medical treatments in Leber’s hereditary optic neuropathy

J Fr Ophtalmol. 2022 Nov;45(8S1):S24-S31. doi: 10.1016/S0181-5512(22)00447-8.

ABSTRACT

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disease caused by a mutation of mitochondrial DNA. LHON targets retinal ganglion cells (RGC), whose axons form the optic nerve. The mutation that leads to LHON is silent until an unknown trigger causes dysfunction of complex I in the mitochondria of RGC. This results in discontinuation of RGC energy production and, eventually, RGC apoptosis. Patients experience bilateral sequential central scotoma over the course of a few months, with a minority recovering some vision more than 1 year after the onset of visual loss. No pharmacological treatment is recommended unless patients are symptomatic in at least one eye, as most LHON mutation carriers never experience visual loss. Research has been focused on treatments that are thought to restore the mitochondrial electron transport chain in RGC in patients with recent disease onset (<1 year). Significant advances have been made in evaluating free radical cell scavengers and gene therapy as potential treatments for LHON. Although promising, the results of clinical trials have been mixed. In patients with chronic visual loss for more than 1 year, treatment that restores vision is yet to be discovered. In this review, we summarize management strategies for patients with LHON before, during, and after the loss of vision, explain the rationale and effectiveness of previous and current treatments, and report findings about emerging treatments.

PMID:36529474 | DOI:10.1016/S0181-5512(22)00447-8