Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy.

Ethambutol-induced optic neuropathy (EON) is a well-recognized ocular complication in patients who take ethambutol as a tuberculosis treatment. The aim of the current study was to investigate the presence of mitochondrial mutations, including and Leber's hereditary optic neuropathy (LHON)-mitochondrial DNA (mtDNA), in patients with EON and to determine their effect on clinical features of these patients. All 47 patients underwent clinical evaluations, including best-corrected visual acuity, fundus examination, and color fundus photography; 37 patients were then followed up over time. Molecular screening methods, including PCR-based sequencing of the gene and LHON-mtDNA mutations, together with targeted exome sequencing, were used to detect mutations. We detected 15 mutations in 18 patients and two LHON-mtDNA mutations in four patients, for an overall mutation detection rate of 46.8%. The mean presentation age was significantly younger in the patients with the mitochondrial mutations (27.5 years) than in those without mutations (48 years). Fundus examination revealed a greater prevalence of optic disc hyperemia in the patients with mutations (70.5%) than without mutations (48%). Half of the patients with mutations and 91% of the patients without mutations had improved vision. After adjusting for confounders, the logistic regression revealed that the patients with optic disc pallor on the first visit ( = 0.004) or the patients with the mitochondrial mutations ( < 0.001) had a poorer vision prognosis. Our results indicated that carriers with mutations might be more vulnerable for the toxicity of EMB to develop EON.