Toxic/Nutritional Optic Neuropathy Clinical Presentation

Toxic and nutritional optic neuropathies resemble each other in terms of their clinical presentation and to most of the optic neuropathies that present simultaneously and bilaterally. When a patient is suspected of having an optic neuropathy, a thorough history is invaluable and should cover diet (eg, how much and what the patient eats); drug/toxin exposure (eg, heavy metals, fumes, solvents); social history (eg, fixed income, amount of money left to buy food after tobacco and alcohol), including tobacco and alcohol use; and occupational background, with details on whether similar cases exist among coworkers. Treatment of any chronic disease or illness should always be elucidated.

A family history should also be taken. Persons with alcoholism are not always forthcoming with their drinking habits; therefore, obtaining these details, along with diet details, from friends or relatives may be more reliable. A review of systems should include inquiries about sensory symptoms in the extremities and about gait disturbances because these might reflect a nutritional or toxic peripheral neuropathy and/or toxic effect upon the cerebellum.

• Dimness of vision is the outstanding symptom. Patients gradually become aware of a blur in the center of their reading vision, which continues to slowly progress. This insidious onset often delays early detection, which, in turn, leads to delayed treatment as well. Initially, only one eye may be involved, but the cloud will eventually appear in both eyes, causing the vision to decline. If the visual loss is unilateral or if a significant difference in the visual acuity is present between the 2 eyes, other diagnoses should be considered. Some patients may notice that certain colors look faded, or they may experience a general loss of color perception. Dyschromatopsia can be the initial symptom in toxic/nutritional optic neuropathy. Neither of these conditions has pain as one of its symptoms. For such cases, other diagnoses should be considered.
• For toxic optic neuropathies, the visual loss may be acute as well as chronic, depending on the insult. Ascertaining whether the onset of the visual symptoms was during or very shortly after exposure to a particular toxin is important. Establishing similar illnesses in coworkers or others exposed to the same drug or chemical also may be helpful.

  • Ethambutol is one drug that commonly is associated with toxic optic neuropathy (not optic neuritis). This is the drug's most serious adverse effect. The optic neuropathy that occurs is dose dependent and duration related.
    • Loss of vision does not tend to occur until the patient has been on the drug for at least 2 months, but there are rare reports of early onset of severe, bilateral visual loss even with appropriate dosing of the drug.^[1] Symptoms generally appear between 4 months to a year. This onset may be sooner if the patient has concurrent renal disease because this will result in reduced excretion of the drug and, therefore, elevated serum levels. Therefore, proper dosing in patients with renal impairment is critical.
    • The toxicity that can occur to the anterior visual pathway from this drug is dose related; patients who are receiving dosages of 25 mg/kg/d or greater are most susceptible to vision loss. However, cases of vision loss, even with much lower doses, have been reported.
  • The clinical presentation is similar to toxic optic neuropathies in general, including dyschromatopsia; some investigators have reported that patients have, in particular, a red-green dyschromatopsia, but others have found predominantly a blue-yellow one. Therefore, appropriate color vision testing is of particular importance in screening patients on this drug.
  • Isoniazid, another antitubercular drug, also can produce toxic optic neuropathy, and patients with concurrent hepatic or renal disease are at higher risk. As with other toxic optic neuropathies, patients present clinically with vision loss, scotomas, and acquired dyschromatopsias. The color vision deficit tends to be less than that of ethambutol.^[2] The drug dosages vary from 200-900 mg/d.
  • Amiodarone, a drug very useful in the treatment of life-threatening arrhythmias, has been implicated as a cause of optic neuropathy, although firm proof of this is still lacking.^[3]
    • Its most common ocular adverse effect, found in almost all patients, is a reversible verticillate keratopathy. The corneal changes very rarely have any visual significance.^[3] Although the optic neuropathy is typically bilateral and symmetric with visual loss and/or field loss, it also may present unilaterally. With this drug, the toxicity to the optic nerve also appears to be dose related, with dosage varying from 200-1200 mg/d. Visual complaints may start 1-72 months after the initiation of treatment and are slowly progressive; the onset of visual loss may also be acute in nature.
    • The optic neuropathy from amiodarone, as discussed in this article, should not be confused with the acute nonarteritic ischemic optic neuropathy-like picture also reported with this drug. However, whether the two clinical pictures are somehow related in patients taking this drug is an issue of tremendous controversy.^[3]

In toxic/nutritional optic neuropathy, visual acuity may vary from minimal reduction to no light perception (NLP) in rare cases. Most patients have 20/200 vision or better.

• When pupils are assessed, one would not expect to find a relative afferent pupillary defect because the optic neuropathy is virtually always bilateral and symmetric. However, in most patients, the pupils are bilaterally sluggish to light.
• Color vision should be assessed because dyschromatopsia is a constant feature in these conditions.
• In nutritional optic neuropathies, the optic disc may be normal or slightly hyperemic in the early stages. In a small group of patients with hyperemic discs, one could find small splinter hemorrhages on or off the disc. Several months to years later in the course of the disease, one might find papillomacular bundle dropout and temporal disc pallor, followed by optic atrophy.
• In the early stages of toxic optic neuropathies, most patients also have normal-appearing optic nerves, but disc edema and hyperemia may be seen in some intoxications, especially in acute poisonings. Papillomacular bundle loss and optic atrophy develop after a variable interval depending on the responsible toxin.
• In ethambutol toxicity, clinically fundi remain normal initially, thereby rendering early detection challenging. Visible atrophy develops later if the drug is not discontinued.
• With isoniazid toxicity, optic nerve swelling has been reported.
• Patients on amiodarone typically present with bilateral optic disc swelling, which can be quite marked, along with flame-shaped hemorrhages. However, unilateral presentations of optic neuropathy have also been reported. The impact on vision associated with the optic neuropathy can be nonexistent, mild,^{[4, 5]} or severe.^[6]

• Causes of nutritional optic neuropathy include tobacco, ethanol, thiamine, and vitamin B-12.^[7]
• Causes of toxic optic neuropathy include chemicals and drugs, such as methanol, ethylene glycol, ethambutol, isoniazid, digitalis, cimetidine, vincristine, cyclosporine, toluene, and amiodarone.