AUTHOR=Zhang Xiao-Hui , Xie Yue , Xu Quan-Gang , Cao Kai , Xu Ke , Jin Zi-Bing , Li Yang , Wei Shi-Hui 

TITLE=Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.754676

DOI=10.3389/fcell.2021.754676

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> 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 <italic>OPA1</italic> 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.</p><p><bold>Methods:</bold> 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 <italic>OPA1</italic> gene and LHON-mtDNA mutations, together with targeted exome sequencing, were used to detect mutations.</p><p><bold>Results:</bold> We detected 15 <italic>OPA1</italic> 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 (<italic>p</italic> = 0.004) or the patients with the mitochondrial mutations (<italic>p</italic> &lt; 0.001) had a poorer vision prognosis.</p><p><bold>Conclusion:</bold> Our results indicated that carriers with <italic>OPA1</italic> mutations might be more vulnerable for the toxicity of EMB to develop EON.</p>