Although the precise deficiency responsible for this disease cannot be determined, its nutritional basis was established beyond doubt during World War II and the Korean War, when innumerable instances were observed in prisoners of war who had been confined for prolonged periods under conditions of severe dietary deprivation. Fisher described the optic nerve lesions in 4 such patients who had died of unrelated causes between 8 and 10 years after the onset of amblyopia. In each case, there was a loss of myelin and axis cylinders restricted to the region of the papillomacular fibers. Of the 4 cases, 3 also showed demyelination of the posterior columns of the spinal cord, no doubt an expression of the associated sensory polyradiculopathy.
In the Western world, a visual disorder indistinguishable clinically and pathologically from that observed in prisoners of war is observed infrequently, mainly among undernourished alcoholics. For many years this had been referred to as tobacco–alcohol amblyopia, with the implication that the visual loss is a result of the toxic effects of alcohol, tobacco, or both. Actually, the evidence strongly suggests that so-called tobacco–alcohol amblyopia is more likely caused by nutritional deficiency than by toxic exposure. A specific nutrient has not been identified, however. There are data in humans and animals that under certain conditions a deficiency of one or more of the B vitamins: thiamine, vitamin B12, and perhaps riboflavin, may cause degenerative changes in the optic nerves, a situation that pertains in the peripheral nerves as well. Part of the confusion in delineating a specific cause has been sporadic outbreaks of optic neuropathy in underdeveloped countries that may have been caused by a disseminated ingested toxin as described further on. The pathology of the optic nerve in amblyopia in the alcoholic has been described by Victor and colleagues (1960).
In the 1960s, a popular theory held that the combined effects of vitamin B12 deficiency and chronic poisoning by cyanide (generated in tobacco smoke) were responsible for “tobacco amblyopia.” Vitamin B12 deficiency is a rare but undoubted cause of optic neuropathy, as noted further on, but the notion that cyanide or other substances in tobacco smoke have a damaging effect on the optic nerves is unsupported (see reviews of Potts and of Victor [1970]). Instances of Leber hereditary optic atrophy, a mitochondrial disorder, may be also mistaken for “tobacco– alcohol amblyopia,” an error that should be made less often because Leber disease disorder can now be identified by mitochondrial DNA testing.
Recent outbreaks of an apparently nutritional or perhaps toxic optic neuropathy occurred in Cuba during the period of 1991 to 1993 and in Tanzania. In both instances the optic neuropathy was frequently associated with peripheral neuropathy. The association of this epidemic with widespread dietary deprivation and the salutary response of both optic and peripheral nerve symptoms to treatment with B vitamins suggests a nutritional causation (see Centers for Disease Control and Prevention and the report of the Cuba Neuropathy Field Investigation Team), but a toxic cause could not be excluded. Shortly thereafter, Plant and colleagues reported on a similar outbreak of optic and peripheral neuropathy from Tanzania.