Methanol-induced optic neuropathy: a still-present problem

Abstract

Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage and loss of function of the optic nerve and retina. Me-ION shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries. The main mechanism underlying the molecular basis of Me-ION is the inhibition of the mitochondrial oxidative phosphorylation process through the binding of the toxic metabolite of methanol—formic acid—with the key enzyme of this process—cytochrome c oxidase. However, other mechanisms, including damage to the eye tissues by oxidative stress causing the intensification of the oxidative peroxidation process with the formation of cytotoxic compounds, as well as an increase in the synthesis of pro-inflammatory cytokines and influence on the expression of key proteins responsible for maintaining cell homeostasis, also play an important role in the pathogenesis of Me-ION. Histopathological changes in the eye tissues are mainly manifested as the degeneration of axons and glial cells of the optic nerve, often with accompanying damage of the retina that may involve all its layers. Despite the development of therapeutic approaches, persistent visual sequelae are seen in 30–40% of survivors. Thus, Me-ION continues to be an important problem for healthcare systems worldwide.

Retinal Toxicity Induced by Chemical Agents

“…Methanol intoxication is a very debilitating condition, most commonly found in developing countries where ingestion of contaminated alcohol in beverages could lead to a variety of systemic symptoms that range from mild intoxication, such as abdominal pain, nausea, vomiting, headache, general weakness, dyspnea and nervous system disturbances, including the retina, to more severe intoxication leading to renal failure, cardiovascular alterations, rhabdomyolysis, convulsions, coma and eventually death [ 151 ]. Visual symptoms might appear hours after ingestion, and they vary widely from progressive decrease in vision to dyschromatopsia, scotoma, and photophobia, accompanied by hyperemic and edematous optic disk acutely, while atrophy and pallor can be observed chronically [ 152 ].…”

Toxic and Nutritional Optic Neuropathies—An Updated Mini-Review

“…The susceptibility of the optic nerve fibers to formate toxicity might be a result of the existence of fewer mitochondria and lower cytochrome oxidase reserves [ 78 , 79 ]. Clinical manifestations regarding ocular damage include the dimming or blurring of vision, photophobia, defects of the visual field, visual hallucinations, a reduction in visual acuity, and even a complete loss of light perception [ 80 ].…”

A young woman with severe bilateral visual loss and putaminal infarcts

“…Formic acid also disrupts oxidative phosphorylation in mitochondria and so can cause toxic optic neuropathy by affecting small very metabolically active axons of ganglion cells in papillomacular bundle. Vision loss typically occurs 12–48 hours after ingestion because of this delay in formic acid accumulation 8. Histopathological studies show demyelination and vacuolation of retinal ganglion cell axons and oedema of adjacent oligodendrocytes and astroglia 8–10.…”

“…Vision loss typically occurs 12–48 hours after ingestion because of this delay in formic acid accumulation 8. Histopathological studies show demyelination and vacuolation of retinal ganglion cell axons and oedema of adjacent oligodendrocytes and astroglia 8–10. Methanol toxicity is also associated with isolated bilateral haemorrhagic infarcts in the putamen, which are similarly specifically vulnerable as highly metabolic structures 11.…”

“…Methanol can also be used in suicide attempts and is the key constituent of windshield washer fluid as antifreeze. Prompt recognition of methanol poisoning is key, as ethanol or fomepizole can be given as an antidote, along with other corrective measures such as haemodialysis and intravenous bicarbonate 8 15. Permanent vision loss results in approximately 40% of cases; the visual prognosis is better in those who have a positive serum ethanol at presentation and those with a lesser degree of acidosis 16 17.…”