Description
The common mechanism underlying most cases of toxic and nutritional optic neuropathy appears to be mitochondrial injury. This impairs ATP formation within the optic nerve, resulting in axoplasmic stasis, optic disc edema and eventual nerve fiber atrophy.
(a) Malnutrition: Excessive consumption of tobacco, alcohol and other medications or substances of abuse is often associated with sustained malnutrition, and it may be difficult to determine the relative contributions to the vision loss. Although the term ‘tobacco-alcohol amblyopia’ has acquired common usage, the dietary deficiencies – particularly in vitamins B1 and B12 – may play a significant role.
(b) Medications & chemicals: Ethambutol is used in the treatment and prevention of tuberculosis. Its association with optic neuropathy may relate to excessive calcium influx into mitochondria. Recovery is often incomplete after treatment cessation. Other substances associated with optic neuropathy include isoniazid (often in combination with ethambutol), quinine, disulfiram, chloramphenicol, lead and cyanide.
Symptoms
Toxic / nutritional optic neuropathy generally presents with gradual, painless, bilateral blurring of vision and altered color sensitivity. Occasionally, alcohol may produce an abrupt loss of vision over hours to days, depending on the amount and type of alcohol consumed. Sensitive elucidation of the patient’s diet, and tobacco and alcohol consumption, is crucial. A family history of adult-onset blindness may suggest an inherited cause such as Leber’s hereditary optic neuropathy.
Signs
Central visual acuity and color vision are impaired. Visual field testing often reveals centrocecal or central scotomas. On ophthalmoscopy, the optic disc most often appears normal. Occasionally there is mild to moderate disc edema with adjacent splinter haemorrhages. Signs of optic atrophy may develop over months to years, with disc pallor typically most pronounced temporally. Methanol toxicity is one condition that often leads to cupping of the disc as well as pallor, from presumed loss of supporting connective tissue at the cribriform plate.
Differential Diagnosis
Leber’s Hereditary Optic Neuropathy, Normal Tension Glaucoma, Traumatic Optic Neuropathy (bilateral), intracranial space-occupying lesions, bilateral macular disease.
See Also
Optic Neuritis.
Management
Additional investigations
Systemic clinical examination may reveal signs of the underlying cause (e.g., signs of malnutrition, liver disease from alcohol abuse, or abnormal sensation and reflexes in vitamin B12 deficiency).
Patients presenting with optic neuropathy are generally investigated with computed tomography or magnetic resonance imaging to exclude space-occupying lesions or cerebrovascular disease.
Blood tests
Indicated blood tests may include hemoglobin (anemia with malnutrition or vitamin B12 deficiency), blood film (macrocytosis with hypersegmented neutrophils in vitamin B12 deficiency – megaloblastic anaemia), liver function tests (deranged in alcoholic liver disease and malnutrition) and serum vitamin B12 and folate (particularly in elderly patients). Significantly, optic nerve and neurological deficits may be well established before the development of macrocytic anemia.
Medications & chemicals
Thiamine occasionally improves vision despite sustained substance abuse. Pyridoxine (vitamin B6, 25 – 100mg/day) is used prophylactically during isoniazid therapy. There is some evidence that copper or zinc may reduce ethambutol-related optic neuropathy.
Advice and review
In the common scenario of optic neuropathy in a malnourished patient with a history of excessive tobacco and/or alcohol consumption, treatment is often empirical – and, unfortunately, often unsuccessful. In general, patients taking systemic medications associated with optic neuropathy should receive routine ocular review, since optic neuropathy may be reversible if the toxin is eliminated at an early stage.
Figure 1
Generalized optic atrophy associated with quinine, showing generalized loss of nerve fibres; thinning & sheathing of retinal arterioles.
Figure 2
Left: Hyperemia & diffuse axonal swelling 9 days after methanol overdose. Right: Same eye, 6 months later, showing optic atrophy and marked acquired disc cupping.
