Antituberculosis medication as a possible epigenetic factor of Leber's hereditary optic neuropathy

Abstract

Antituberculosis medication may be an epigenetic factor of LHON in patients with a primary LHON mutation. This risk should be recognized by physicians and LHON carriers.

Drug-Related Mitochondrial Optic Neuropathies

“…Ethambutol and erythromycin have also been suggested to trigger LHON (85)(86)(87). Similarly, ethambutol has been linked to visual loss in a patient with dominant optic atrophy (DOA) with an OPA1 mutation (88).…”

Sibling Ethambutol Optic Chiasmopathy

“…Indeed, cases of LHON-related vision loss have been reported in patients taking ethambutol, with some authors postulating that ethambutol may be an epigenetic trigger for LHON. 4 Although this remains controversial, with some authors finding no synergism between the two, LHON should be considered in atypical cases of EON, including those with early disc hyperaemia, severe late optic atrophy, continuing visual decline following ethambutol cessation, and advanced age at onset, as in our cases. [4][5][6] Furthermore, ethambutol has been associated with cases of OPA1-related optic atrophy and one case of CMT2A2-related optic atrophy with systemic signs of muscle weakness.…”

“…4 Although this remains controversial, with some authors finding no synergism between the two, LHON should be considered in atypical cases of EON, including those with early disc hyperaemia, severe late optic atrophy, continuing visual decline following ethambutol cessation, and advanced age at onset, as in our cases. [4][5][6] Furthermore, ethambutol has been associated with cases of OPA1-related optic atrophy and one case of CMT2A2-related optic atrophy with systemic signs of muscle weakness. [7][8][9] With differing pathophysiology, LHON impairing oxidative phosphorylation, whilst OPA1 and CMT2A2 disturbing mitochondrial fusion, these reports strengthen the suggestion of an epigenetic, or synergistic, effect between mitochondrial genetics and ethambutol in the development of EON or optic atrophy.…”

Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

“…An onset of LHON can be not only associated with but also triggered by many factors, including diabetes, 11,21 optic neuritis, 22 anti-tuberculous medications, 10,23,24 antiretroviral therapy for human immunodeficiency virus, 25,26 carbon monoxide poisoning, 27 solvent exposure, 28 smoking, 1,11,14,29–31 trauma, 11,12,14,32,33 and even an increase in the intraocular pressure. 11,12 For example, a 58-year-old man had an onset of visual loss 1 year after an elevation in his intraocular pressures was first recorded, and a 11778G→A mutation was identified.…”