Curbside Consultation

How Do You Manage Toxic and Nutritional Optic Neuropathies?

Julie Falardeau, MD, FRCSC

A 24-year-old man has been referred for progressive bilateral visual loss. On Thanksgiving of 2002 he noted blurring of vision OU especially affecting central vision. He described a “hole” in his vision bilaterally as if a “light bulb went off” in vision centrally. There has been no exposure to toxins or animals, eye pain, or headaches.  He smokes one pack of cigarettes daily (for the past 5 years), drinks 24 beers or more weekly, and lives on his own and does not eat regular meals. There is no family history of ophthalmologic diseases. His exam reveals visual acuity of 20/200 OD and 20/400 OS. There are bilateral cecocentral scotomas and the optic nerves are pale temporally bilaterally. What diagnoses should be considered?

Toxic and nutritional optic neuropathies are typically characterized by bilateral, simultaneous visual impairment with progressive loss of visual acuity, dyschromatopsia, central or cecocentral scotoma, papillomacular bundle damage, and temporal optic disc atrophy.  When a patient presents with this constellation of signs, a thorough history is crucial. An extensive history may be the best way to uncover the circumstances that involve toxic/nutritional optic neuropathy. I would emphasize diet, tobacco and alcohol use, and drug and toxin exposure. Treatment of any chronic illness or disease should be elucidated.

Nutritional optic neuropathy typically involves deficiencies in vitamin B12 (cobalamin), vitamin B1 (thiamine), vitamin B2 (riboflavin), and folic acid. Optic neuropathies from pure nutritional deficiencies have been reported in strict vegan patients. Certain weight reduction methods, including gastric bypass surgery, may result in deficits of vitamins and can be complicated by vision loss from bilateral optic neuropathy. Vitamin B12 deficiency is the most common cause of nutritional amblyopia and generally arises in 3 different clinical settings: 1) pernicious anemia, 2) previous history of partial or complete stomach or ileum removal, and 3) strict vegan diet. Since optic neuropathies due solely to nutritional deficiencies remain rare in North America, it is important to ask about tobacco use and alcohol consumption. Nutritional optic neuropathy is clearly more common among tobacco and alcohol abusers. Numerous other agents have also been identified as a potential cause of toxic optic neuropathy through presumed direct metabolic impairments but the main one to consider is ethambutol (Table 26-1).

Progressive dimness of vision is the classic symptom. Patients become aware of gradual blurred central vision that is slowly progressive. This visual loss is painless, bilateral, and simultaneous though the involvement can be asymmetric in the acute phase. Color vision should be tested since dyschromatopsia is a constant feature and occurs early. There is usually no relative afferent pupillary defect since the disease is almost always bilateral and symmetric. Most patients will present with normal-appearing optic discs in the early stages. Optic disc edema may be seen in some toxic optic neuropathies such as those caused by amiodarone and isoniazid toxicity. Papillomacular bundle loss and optic atrophy (especially temporal atrophy) finally develop in the chronic stages. Formal visual field testing with either static or kinetic perimetry is essential in the evaluation of a patient suspected of suffering from toxic/nutritional optic neuropathy. Bilateral central or cecocentral scotomas with preservation of the peripheral visual field are characteristic of these optic neuropathies.

A family history of bilateral vision loss should be noted and investigated since Leber’s hereditary optic neuropathy can present in a similar way. A detailed review of the system should inquire about peripheral sensory symptoms and gait disturbance because these might reflect a nutritional/toxic peripheral neuropathy.

The differential diagnosis of toxic/nutritional optic neuropathy may be challenging. Other conditions should be considered, including the following:

                * Compressive optic neuropathy

                * Leber’s hereditary optic neuropathy

                * Dominant inherited optic neuropathy

                * Maculopathy/macular dystrophy

                * Syphilitic optic neuropathy

                * Radiation optic neuropathy

                *Bilateral inflammatory or demyelinating optic neuropathy

                * Infiltrative optic neuropathy

I would suggest that your patient undergo laboratory studies, including a complete blood count with differential, serum B12, red blood cell folate, and syphilis serology. Leber’s mitochondrial DNA mutation testing and heavy metal screening should be considered if the etiology remains unknown after the initial work-up. Since there are many examples of bilateral cecocentral scotoma secondary to compressive or infiltrative lesions, a neuroimaging study should be performed even if toxic/nutritional optic neuropathy is highly suspected. Magnetic resonance imaging (MRI) with and without contrast enhancement and fat suppression remains the study of choice to rule out a compressive or infiltrative process involving the optic chiasm or optic nerves.

The first step in managing toxic optic neuropathy is to remove the offending agent. This may cause some reversal of the process, especially if removed early in the course of the optic nerve dysfunction. Other than stopping the drug, no specific treatment is available for these optic neuropathies. For patients in whom the diagnosis of tobacco-alcohol amblyopia is suspected, it cannot be overemphasized that stopping, or at least reducing, tobacco and alcohol consumption is critical to their recovery. For nutritional optic neuropathies, improved nutrition is essential. I strongly recommend comanaging these patients with an internist. Medical therapy includes vitamin supplementation with thiamine, folic acid, multivitamins, and, in case of pernicious anemia, vitamin B12 injections monthly for several months. The elimination of any causative agent such as alcohol is also a key factor for potential recovery. The visual prognosis is typically poor if optic atrophy is already present.

I think that most likely your patient has a nutritional optic neuropathy and needs to quit smoking and stop alcohol consumption. In a young man with this clinical picture, however, Leber’s hereditary optic neuropathy is also of concern.

Summary

                * Toxic and nutritional optic neuropathies are typically characterized by bilateral, simultaneous visual impairment with progressive loss of visual acuity, dyschromatopsia, central or cecocentral scotoma, papillomacular bundle damage, and temporal optic disc atrophy. 

                * Since bilateral cecocentral scotoma may occur secondary to compressive or infiltrative lesions, a neuroimaging study should be performed even if toxic/nutritional optic neuropathy is highly suspected.

                * Leber’s mitochondrial DNA mutation testing should be considered if the etiology of a presumed toxic/nutritional optic neuropathy remains unknown after the initial work-up.

Bibliography

Lloyd MJ, Fraunfelder FW. Drug-induced optic neuropathies. Drugs Today. 2007;43:829-838.

Orsaaud C, Roche O, Dufier JL. Nutritional optic neuropathies. J Neurol Sci. 2007;262:158-164.

Phillips PH. Toxic and deficiency optic neuropathies. In: Miller NR, Newman NJ, eds. Walsh and Hoyt’s Clinical Neuro-Ophthalmology. 6th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005:447-463.

Sadun AA. Metabolic optic neuropathies. Semin Ophthalmol. 2002;17:29-32.