Drug-Related Mitochondrial Optic Neuropathies

Abstract

Mitochondrial optic neuropathies are increasingly recognized as a spectrum of conditions that reach a similar end point by compromising a common pathway of mitochondrial dysfunction. Clinicians should be aware of drugs that can cause a MON. Prompt recognition of this association is critical in preventing irreversible, profound visual loss.

Une cause rare de neuropathie optique : le manioc

“…Plusieurs agents toxiques ont été rapportés, notamment le cyanure et le méthanol issu d'alcools de mauvaise qualité et de préparation artisanale [15]. Enfin, les causes iatrogènes de neuropathie optique sont nombreuses, parmi lesquelles nous pouvons citer un antituberculeux (éthambutol) pour lequel une surveillance ophtalmologique est recommandée [16] et l'amiodarone dont le mécanisme physiopathologique est cependant moins bien compris [17]. Compte tenu de l'absence d'antécédent familial et la négativité des examens génétiques chez nos patients, l'hypothèse toxique ou carentielle était donc à privilégier.…”

Vitamin B Deficiencies in a Critically Ill Autistic Child With a Restricted Diet

“…The exact mechanism responsible for associated seizures remains unknown; animal models suggest alterations in the metabolism of γ-aminobutyric acid, as well as other amino acids. 17 Well-recognized organ involvement associated with mitochondrial dysfunction includes NASH, 18 optic neuropathy, 19 and leukoencephalopathy. 20 Their presence in our patient may reflect the metabolic complications of micronutrient deficiencies leading to mitochondrial dysfunction or alternatively be manifestations of an as yet undiagnosed, underlying mitochondrial disorder.…”

Ethambutol: friend or foe?

“…ON develops in 50% of patients taking EMB with doses of 60-100 mg/kg/day, while EON develops in 6% of patients at 25 mg/kg/day and in only 1% for those using £15 mg/kg/day [5,13]. Therefore, we prefer the dose of £15 mg/kg/day.…”

“…As to the examination itself evaluating the visual acuity, color vision, Amsler grid and visual fields are the key tests to perform [5]. The visual field test to consider is 10-2 Humphrey Visual Field testing size III with best visual acuity.…”

“…Although the pathophysiology of EON is not fully understood, the proposed mechanisms involve the chelating effect of the drug on metal ions, most notably zinc and copper contained in prokaryotic ribosomes [4]. Due to the similarity of bacterial and mammalian mitochondrial DNA, EMB disrupts oxidative phosphorylation at the level of iron-containing complex I and copper-containing complex IV of the electron-transporting chain [5]. EMB decreases the levels of copper available for cytochrome oxidase c, causing a sustained impairment in energy production that eventually leads to accumulation of oxygen reactive species and subsequent apoptosis and resultant ON degeneration [3,6].…”