Toxic/Nutritional Optic Neuropathy

Temporal pallor and nerve fiber layer loss in a young woman with toxic neuropathy.

Signs and symptoms: Toxic/nutritional optic neuropathy often presents as a painless, progressive, bilat eral, symmet- rical visual disturbance with variable optic nerve pallor. Pallor in the temporal quadrant is most common with this condition. The patient may manifest reduction in visual acuity (20/50­ 20/200), loss of central visual field (usually relative cecocentral scotoma) and reduced color per ception.

Pathophysiology: Toxic optic neuropathy may result from exposure to neuro-poisonous substances in the environment, ingestion of certain foods or other materials containing toxic substances, or from elevated serum drug levels. Nutritional deficiencies or metabolic disorders may also cause this disease. In most cases, the cause of the toxic neuropathy impairs the tissue's vascular supply or metabolism.

Among the common offenders is tobacco, which produces metabolic deficiencies as part of the systemic nicotine cascade. Alcohol, like tobacco smoke, produces its toxic effects through metabolic means. Chronic exposure typically leads to vitamin B-12 or folate deficiency. Over time, these deficiencies cause accumulations of formic acid. Both formic acid and cyanide inhibit the electron transport chain and mitochondrial function, resulting in disruption of ATP production and ultimately impairing the ATP-dependent axonal transport system.

Numerous other agents can produce toxic optic neuropathy (see table below). Methanol (wood alcohol) can cause focal retrolaminar optic nerve delamination.

Agents that Can Cause Toxic Optic Neuropathy   Methanol Ethylene glycol (antifreeze) Chloramphenicol Isoniazid Ethambutol Digitalis Chloroquine Streptomycin Amiodarone Quinine Vincristine and methotrexate (chemotherapy medicines) Sulfonamides Melatonin with Zoloft (sertraline, Pfizer) in a high-protein diet Carbon monoxide Lead Mercury Thallium (alopecia, skin rash, severe vision loss) Malnutrition with vitamin B-1 deficiency Pernicious anemia (vitamin B-12 malabsorption phenomenon) Radiation (unshielded exposure to >3,000 rads).

Management: The first step in managing toxic-nutritional optic neuropathy--as with any toxic process--is to remove the offending agent. This may cause some reversal of the process. Medical therapy includes vitamin supplementation with thiamine 100mg bid; folate 1mg qd; a multivitamin qd and, in the case of pernicious anemia, vitamin B-12 1,000mg, monthly for at least six months. Pyroxidine 25-100mg/day may help stabilize or reverse isoniazid-caused toxic neuropathy.

Evaluation for toxic optic neuropathy includes a complete ocular examination with color vision testing and threshold visual field testing. Also refer the patient for complete physical and laboratory studies such as a complete blood count with differential, serum B-1, B-12 and folate levels, a heavy metal screening (lead, thallium) and test for the Leber's mitochondrial DNA mutation.

Clinical Pearls:

• An extensive history may be the best way to uncover circumstances and situations that involve toxic neuropathy.
• Differential diagnosis of toxic neuropathy may be challenging. Rule out other types of optic neuropathy (see table below).