Toxic/Nutritional Optic Neuropathy

Updated: Feb 21, 2023
  • Author: Andrew A Dahl, MD, FACS; Chief Editor: Hampton Roy, Sr, MD  more...
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The anterior visual pathway is susceptible to damage from toxins or nutritional deficiency. These disorders tend to be classified under the heading toxic/nutritional optic neuropathy, a syndrome characterized by papillomacular bundle damage within the optic nerves, central or cecocentral scotoma, and reduction of color vision. Both toxicity and malnutrition, acting either independently or together, have been implicated in the pathogenesis of these disorders. Although these problems have been classified as optic neuropathies, in most of these entities, the primary lesion has not actually been localized to the optic nerve and may possibly originate in the retinal ganglion cells or nerve fiber layers, chiasm, or even the optic tracts.



The exact mechanism by which nutritional deficits damage the optic nerve has not been elucidated. Although the etiology is likely multifactorial, most clinicians agree that in patients who abuse ethanol and tobacco, malnourishment often is present, and undernutrition, rather than direct toxicity, is the principal cause of the visual loss. Specific deficiencies of vitamin B-12 (cyanocobalamin), thiamine (vitamin B-1), other B-complex vitamins (riboflavin, niacin, and pyridoxine), and folic acid, as well as reduced systemic levels of other proteins with sulfur-containing amino acids, may play a role.

Whether tobacco or ethanol has a direct toxic effect on the optic nerve remains unclear. Why certain other agents are toxic to the optic nerve, particularly the portion that comprises the papillomacular bundle, also remains largely unestablished. Whether an unusual configuration of the vascular supply of the optic nerve head in certain individuals predisposes them to the accumulation of toxic agents has been questioned.

Ethyl alcohol, like tobacco, produces its toxic effects through metabolic means. Extended high-dosage exposure may lead to folate or vitamin B-12 deficiency, resulting in accumulation of formic acid, inhibiting the electron transport chain and mitochondrial function, ultimately resulting in impairment of adenosine triphosphate (ATP)–mediated axonal transport within nerves, including the optic nerve.

The toxin methyl alcohol (methanol) causes focal delamination of the optic nerve in animal experiments and in humans.

All of these deficiencies or toxicities affect mitochondrial oxidative phosphorylation. In essence, the toxic and nutritional optic neuropathies actually are acquired mitochondrial optic neuropathies, similar in clinical picture to congenital mitochondrial optic neuropathies.

It has been hypothesized that the chelating properties of ethambutol are what contribute to its neurotoxicity, but this has yet to be proven. The mechanism of the neurotoxicity that occurs from the cardiac antiarrhythmic amiodarone also remains unclear, with researchers believing that it may relate to lipid accumulation in optic nerve axons, with subsequent impedance of axoplasmic flow.




United States

Toxic and nutritional optic neuropathies are not common in the United States. In the general population, nutritional amblyopia is more common among tobacco and alcohol abusers and those who are undernourished. Toxic optic neuropathies usually are associated with exposure of employees in a workplace, ingestion of materials/foods containing toxic substances, or systemic medications.


Nutritional optic neuropathy is definitely more prevalent in regions of famine, such as in Africa, where it may take on epidemic proportions.


Morbidity of these disorders depends on risk factors, the underlying etiology, and the duration of symptoms before the institution of treatment. A patient with advanced optic atrophy is less likely to recover visual function than a patient who does not have such pathologic changes.


These disorders have no racial predilection. All races are susceptible.


These disorders are found equally in both males and females.


Any age may be affected by toxic optic neuropathies, but nutritional optic neuropathies are very rare in children, perhaps since drinking and smoking are much less frequent in this age group. Historically, toxic optic neuropathy was formerly seen in children with chronic pulmonary conditions, such as cystic fibrosis, when treated with chloramphenicol.



If patients with nutritional optic neuropathy are compliant with the treatment regimen, and unless the loss of vision is already far advanced, the prospect for recovery or at least improvement is excellent, except for the most chronic cases. However, the rate of recovery varies from a few weeks to several months. The prognosis is also better if treatment is initiated in the first few months after the onset of symptoms. Visual acuity tends to recover before color vision. When recovery has been complete, recurrences are unusual. Although extremely rare, cases of spontaneous improvement of vision have been reported without patient cooperation.

For toxic optic neuropathies, when the responsible toxin is discontinued, vision usually recovers to normal over several days to weeks. However, this does depend in large part on the nature of the offending agent and on its total exposure before it was removed.


Patient Education

Patients must be alerted to report any visual problems to their ophthalmologist immediately if they are taking ethambutol, isoniazid, or amiodarone.