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Tobacco Amblyopia
Tobacco Amblyopia Joseph F. Rizzo III, M.D., and Simmons Lessefl, M.D.
Tobacco amblyopia, once an important cause of bilateral optic neuropathy, has become so rare in the United States that some investigators doubt its existence. However, we treated two men who appeared to have this disorder. These two patients demonstrate that tobacco amblyopia can develop without malnutrition, alcoholism, or disordered vitamin B12 metabolism. Both patients recovered, one with cessation of smoking and the other with intramuscular administration of hydroxocobalamin despite continued smoking. SMOKING is a factor in several debilitating and fatal diseases, but the only eye disease in which smoking has been implicated is a bilateral optic neuropathy identified in the 19th century. By the end of that century, thousands of cases of visual loss had been ascribed to smoking. Inexplicably, the incidence of the disease has been declining without a concomitant decline in the use of tobacco. Samples and Younge! reviewed the records of the Mayo Clinic during a recent 25-year interval and identified only ten examples of tobacco amblyopia. Potts! did not encounter one case of the disease among his "many tens of thousands of eye patients" seen since the Second World War. In the middle of the 19th century, Mackenzie" could write of tobacco amblyopia that " ... chronic cases can be met with every day at any Eye Infirmary ...." and from the 1913 to 1926 interval, Traquair'" estimated that the disorder accounted for fully 1 % of the diagnoses at the Royal Infirmary in Edinburgh, Scotland. Few detailed case descriptions of tobacco amblyopia have been provided in recent published reports.
Accepted for publication April 13, 1993. From the Department of Ophthalmology, Harvard Medical School and the Neuro-Ophthalmology Unit, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Reprint requests to Joseph F. Rizzo III, M.D., Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02114.
84
We treated two men whose clinical and laboratory findings suggested they had this disease, which is now thought to be rare. We desired to document with ample detail the continued presence of this remediable cause of neurogenic visual loss.
Case Reports Case 1
A 43-year-old male construction worker was examined in February 1987 because of progressive loss of vision in both eyes. Eighteen months previously a metal foreign body was removed from his cornea. At that time visual function was normal and the foreign body was removed without apparent residua. Ten weeks before referral he developed progressive loss of vision in the left eye, followed within several weeks by visual loss in the right eye. There were no other symptoms. The patient had abused alcohol between 1975 and 1985 but subsequently abstained. He maintained a balanced and adequate diet. For 25 years he had chain-smoked approximately 15 large cigars daily. He was in good general health, took no medications, and was not exposed to toxic substances other than asbestos at work. His family history was noncontributory for eye, hematologic, or neurologic disorders. Visual acuity was correctable to R.E.: 20/25 and L.E.: 20/100. Color vision (Ishihara) was normal in the right eye and markedly impaired in the left eye. There were bilateral visual field defects (Fig. 1), but no other abnormalities were detected by neuro-ophthalrnic examination. General physical and neurologic examinations disclosed that the patient was well nourished and had mild chronic obstructive pulmonary disease. Results of a complete blood cell count, a serologic test for syphilis, urinalysis, and tests of liver function were normal, as were the erythrocyte sedimentation rate and serum folate, vitamin B12, serum protein, serum electrolyte, blood urea nitrogen, serum creatinine, and
©AMERICAN JOURNAL OF OPHTHALMOLOGY
116:84-87,
JULY,
1993
Vol. 116, No.1
Tobacco Amblyopia
85
Fig. 1 (Rizzo and Lessell). Case 1. Goldmann visual field with 14e and l ze stimuli. The scotomas are to the l ze stimulus.
plasma glucose levels. Thoracic radiography disclosed no abnormalities and an antinuclear antibody titer was negative. Treatment was initiated with one intramuscular injection of 200 J1.g of hydroxocobalamin and cessation of smoking. He also began to take 1,000 J1.g of vitamin BIz daily by mouth. Four days later he sensed improvement; visual acuity was R.E.: 20/15 and L.E.: 20/100 and color vision was markedly improved. Two weeks later the visual acuity could be corrected to 20/70 in the left eye. Three weeks later, visual acuity was R.E.: 20/15 and L.E.: 20/25 with normal color vision and improved visual fields. By August 1987, visual acuity was 20/15 in each eye with full visual fields, normal color vision, and normal fundi. He had maintained this level of visual function and was still abstaining from smoking when last examined in May 1988.
Case 2 A 77-year-old male retired banker was examined in February 1990 because of visual loss. He had been in good health except for chronic osteomyelitis of the leg and bilateral hip replacements. At 67 years of age, he began to have painless progressive visual loss in the right eye, which was ascribed to a cataract. Cataract extraction eight years later improved his visual acuity but failed to restore normal sight. Ten months before referral he became
aware of subnormal vision in his left eye. He had no pain or other symptoms. For many years, he smoked over five ounces of pipe tobacco a week and consumed four or five ounces of alcohol a day. However, he maintained a balanced and adequate diet. He was taking no medications and was not exposed to toxic substances. His family history was noncontributory for eye, neurologic, and hematologic disorders. His visual acuity was R.E.: 20/40 and L.E.: 20/70. He could only see the control plate in the Ishihara series test plates and had visual field defects in both eyes (Fig. 2). There was posterior chamber pseudophakia in the right eye. The left eye had a cataract that was insufficiently dense to explain the poor visual acuity. Both optic disks appeared slightly atrophic. Neurologic and general medical examinations showed no abnormalities, He appeared to be well nourished. Cranial and orbital computed tomography with contrast, and cranial magnetic resonance imaging without gadolinium showed only generalized cortical atrophy of the cerebral hemispheres. In both eyes the pattern visual-evoked response P100 latencies were abnormal (126 milliseconds). Results of a complete blood cell count, urinalysis, routine blood chemistries, Schilling test, and a serologic test for syphilis were normal, as were the erythrocyte sedimentation rate, serum folate, and vita-
86
AMERICAN JOURNAL OF OPHTHALMOLOGY
July, 1993
Fig. 2 (Rizzo and Lessell). Case 2. Goldmann visual field with III 4e and I4e stimuli. The scotomas are to the Ize stimulus.
min B12 levels. Anti-intrinsic factor antibody was not detected. Weekly injections of 1,000 ~g of hydroxocobalamin were started. Within several weeks the patient noticed improved visual acuity despite his usual consumption of alcohol and tobacco. Three months after the injections were begun, his visual acuity was R.E.: 20/25 and L.E.: 20/30. He could see several Ishihara test plates with each eye and his visual fields were improved. When most recently examined in May 1992, he had a relative paracentral scotoma in the right eye and a normal visual field in the left eye. Visual acuity had declined to 20/30 in each eye from an epiretinal membrane in the right eye and a cataract in the left eye. He never modified his smoking or drinking habits.
Discussion
To a great extent, neuro-ophthalmology has become the specialty that evaluates neurogenic visual loss in patients with neuroimaging studies that disclose no abnormalities. Tobacco amblyopia is one of the diagnoses that is occasionally invoked by referring physicians in such cases, but the final diagnosis is nearly always something else. The patients described in our study represented the only two convincing ex-
amples of tobacco amblyopia seen at the Massachusetts Eye and Ear Infirmary between 1984 and 1992. For the most part, at initial examination our patients had characteristic features of tobacco amblyopia, which is a disease of middle-aged and elderly men who smoke pipes or cigars. Both eyes are affected, although not always symmetrically, by painless, progressive loss of vision with centrocecal scotomas and dyschromatopsia. Recovery of vision can follow cessation of smoking, as in our first patient, or can occur with hydroxocobalamin therapy despite undiminished smoking as in our second patient. The rapidity with which they responded was remarkable. Some experts who doubt that smoking is responsible for this disease indict malnutrition instead.v" Malnutrition would not seem a likely explanation for the loss of vision in our patients. A careful nutritional history indicated that they regularly ate well and both of them looked well nourished. They were also free of neurologic or hematologic stigmata of nutritional deficiency. The pathogenesis of tobacco amblyopia has yet to be elucidated. Nicotine does not appear to have a role and the correlation between the type or amount of tobacco consumed and the occurrence of visual loss is imperfect. Because even in the most prevalent period of the dis-
Vol. 116, No.1
Tobacco Amblyopia
ease, tobacco amblyopia affected only a miniscule percentage of smokers, a multifactorial pathogenesis has been postulated. A multifactorial pathogenesis might also explain why the disease typically appears only after many years of smoking, as it did in our patients. Alcohol consumption has received considerable attention as an etiologic cofactor. The disorder is even designated tobacco-alcohol amblyopia by many current investigators. Certainly, many heavy smokers also use alcohol to excess. However, there is no convincing evidence that ethyl alcohol is toxic to the anterior visual pathway, and several large reviews have documented the occurrence of the disease in smokers who were temperate. Our first patient was abstemious when his vision became impaired and the second recovered his vision despite failure to curb his drinking. Disordered vitamin B12 metabolism has also been suspected in the origin of tobacco amblyopiaY Patients with pernicious anemia may develop an optic neuropathy, sometimes as the herald symptom of the disease." In other B12 deficiency states, such as diphyllobothriasis, patients are predisposed to an optic neuropathy and smoking may be an additional risk factor in these individuals.'? There is also evidence that smoking impairs the absorption of vitamin B12 in patients with tobacco amblyopia." However, most patients with tobacco amblyopia have vitamin B12 levels well within the normal range, as was true in both of our patients. The second patient also had normal results of a Schilling test and had no anti-intrinsic factor antibodies. Whereas earlier methods to quantitate vitamin B12 levels were inexact because of their tendency to report spuriously increased levels, the current standard uses intrinsic factor as the binding agent and has high specificity for B12 • For these reasons and the lack of neurologic signs of subacute combined degeneration (peripheral neuropathy, mental status changes, and deficits in proprioception) that result from vitamin B12 deficiency, there is no reason to believe that disordered vitamin B12 metabolism had a role in causing their optic neuropathy. The absence of anemia cannot be used to exclude a diagnosis of B12 deficiency because this association depends on other factors, such as iron levels, and is therefore unreliable. Recognition of tobacco amblyopia partially depends on discovering a centrocecal scotoma,
87
which is an unusual but nonspecific clinical sign. Centrocecal scotomas may be found in patients who have optic neuritis, nutritional optic neuropathy, Leber's hereditary optic neuropathy, cilioretinal artery occlusion, and toxic and sundry other optic neuropathies. Centrocecal scotomas are easiest to recognize with a tangent screen or Goldmann perimeter, although automated visual fields can be helpful especially if directed or customized for the central region. Bilateral visual loss consequent to smoking (tobacco amblyopia), although rare, is still encountered. As illustrated by our two patients with the disorder, malnutrition, alcoholism, or disordered vitamin B12 metabolism need not be present. Cessation of smoking or treatment with hydroxocobalamin can effect recovery.
References 1. Samples, J. R., and Younge, B. R.: Tobacco-alcohol amblyopia. J. Clin. Neuro. Ophthalmol. 1:213, 1981. 2. Potts, A. M.: Tobacco amblyopia. Surv. Ophthalmol. 17:313, 1973. 3. Mackenzie, W.: A Practical Treatise on Diseases of the Eye, ed. 4. London, England, Longman, Brown, Green, and Longmans, 1854, p. 1067. 4. Traquair, H. M.: Tobacco amblyopia. Lancet 2:1173,1928. 5. - - : Toxic amblyopia, including retrobulbar neuritis. Trans. Ophthalmol. Soc. U. K. 50:351,1930. 6. Dreyfus, P. M.: What is the cause of tobaccoalcohol amblyopia? In Brockhurst, R. J., Boruchoff, S. A., Hutchinson, B.T., and Lessell, S.: Controversy In Ophthalmology. Philadelphia, W. B. Saunders, 1977, pp. 844-850. 7. Victor, M.: Tobacco amblyopia, cyanide poisoning and vitamin Bl2 deficiency. In Smith, J. L.: Neuroophthalmology. Hallandale, Florida, Huffman, 1970, pp.33-48. 8. Heaton, J. M., McCormick, A. J. A., and Freeman, A. G.: Tobaccoamblyopia. A clinical manifestation of vitamin B12 deficiency. Lancet 2:286, 1958. 9. Cohen, H.: Optic atrophy as a presenting sign in pernicious anemia. Lancet 2:1202, 1936. 10. Bjorkenheim, B.: Optic neuropathy caused by vitamin B12 deficiency in carriers of the fish tapeworm, diphyllobothrium latum. Lancet 1:688, 1966. 11. Watson-Williams, E. J., Bottomley, A. c.. Ainley, R. G., and Philips, C. 1.: Absorption of vitamin B12 in tobacco amblyopia. Br. J. Ophthalmol. 53:549, 1969.
Tobacco amblyopia, once an important cause of bilateral optic neuropathy, has become so rare in the United States that some investigators doubt its existence. However, we treated two men who appeared to have this disorder. These two patients demonstrate that tobacco amblyopia can develop without malnutrition, alcoholism, or disordered vitamin B12 metabolism. Both patients recovered, one with cessation of smoking and the other with intramuscular administration of hydroxocobalamin despite continued smoking. SMOKING is a factor in several debilitating and fatal diseases, but the only eye disease in which smoking has been implicated is a bilateral optic neuropathy identified in the 19th century. By the end of that century, thousands of cases of visual loss had been ascribed to smoking. Inexplicably, the incidence of the disease has been declining without a concomitant decline in the use of tobacco. Samples and Younge! reviewed the records of the Mayo Clinic during a recent 25-year interval and identified only ten examples of tobacco amblyopia. Potts! did not encounter one case of the disease among his "many tens of thousands of eye patients" seen since the Second World War. In the middle of the 19th century, Mackenzie" could write of tobacco amblyopia that " ... chronic cases can be met with every day at any Eye Infirmary ...." and from the 1913 to 1926 interval, Traquair'" estimated that the disorder accounted for fully 1 % of the diagnoses at the Royal Infirmary in Edinburgh, Scotland. Few detailed case descriptions of tobacco amblyopia have been provided in recent published reports.
Accepted for publication April 13, 1993. From the Department of Ophthalmology, Harvard Medical School and the Neuro-Ophthalmology Unit, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Reprint requests to Joseph F. Rizzo III, M.D., Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02114.
84
We treated two men whose clinical and laboratory findings suggested they had this disease, which is now thought to be rare. We desired to document with ample detail the continued presence of this remediable cause of neurogenic visual loss.
Case Reports Case 1
A 43-year-old male construction worker was examined in February 1987 because of progressive loss of vision in both eyes. Eighteen months previously a metal foreign body was removed from his cornea. At that time visual function was normal and the foreign body was removed without apparent residua. Ten weeks before referral he developed progressive loss of vision in the left eye, followed within several weeks by visual loss in the right eye. There were no other symptoms. The patient had abused alcohol between 1975 and 1985 but subsequently abstained. He maintained a balanced and adequate diet. For 25 years he had chain-smoked approximately 15 large cigars daily. He was in good general health, took no medications, and was not exposed to toxic substances other than asbestos at work. His family history was noncontributory for eye, hematologic, or neurologic disorders. Visual acuity was correctable to R.E.: 20/25 and L.E.: 20/100. Color vision (Ishihara) was normal in the right eye and markedly impaired in the left eye. There were bilateral visual field defects (Fig. 1), but no other abnormalities were detected by neuro-ophthalrnic examination. General physical and neurologic examinations disclosed that the patient was well nourished and had mild chronic obstructive pulmonary disease. Results of a complete blood cell count, a serologic test for syphilis, urinalysis, and tests of liver function were normal, as were the erythrocyte sedimentation rate and serum folate, vitamin B12, serum protein, serum electrolyte, blood urea nitrogen, serum creatinine, and
©AMERICAN JOURNAL OF OPHTHALMOLOGY
116:84-87,
JULY,
1993
Vol. 116, No.1
Tobacco Amblyopia
85
Fig. 1 (Rizzo and Lessell). Case 1. Goldmann visual field with 14e and l ze stimuli. The scotomas are to the l ze stimulus.
plasma glucose levels. Thoracic radiography disclosed no abnormalities and an antinuclear antibody titer was negative. Treatment was initiated with one intramuscular injection of 200 J1.g of hydroxocobalamin and cessation of smoking. He also began to take 1,000 J1.g of vitamin BIz daily by mouth. Four days later he sensed improvement; visual acuity was R.E.: 20/15 and L.E.: 20/100 and color vision was markedly improved. Two weeks later the visual acuity could be corrected to 20/70 in the left eye. Three weeks later, visual acuity was R.E.: 20/15 and L.E.: 20/25 with normal color vision and improved visual fields. By August 1987, visual acuity was 20/15 in each eye with full visual fields, normal color vision, and normal fundi. He had maintained this level of visual function and was still abstaining from smoking when last examined in May 1988.
Case 2 A 77-year-old male retired banker was examined in February 1990 because of visual loss. He had been in good health except for chronic osteomyelitis of the leg and bilateral hip replacements. At 67 years of age, he began to have painless progressive visual loss in the right eye, which was ascribed to a cataract. Cataract extraction eight years later improved his visual acuity but failed to restore normal sight. Ten months before referral he became
aware of subnormal vision in his left eye. He had no pain or other symptoms. For many years, he smoked over five ounces of pipe tobacco a week and consumed four or five ounces of alcohol a day. However, he maintained a balanced and adequate diet. He was taking no medications and was not exposed to toxic substances. His family history was noncontributory for eye, neurologic, and hematologic disorders. His visual acuity was R.E.: 20/40 and L.E.: 20/70. He could only see the control plate in the Ishihara series test plates and had visual field defects in both eyes (Fig. 2). There was posterior chamber pseudophakia in the right eye. The left eye had a cataract that was insufficiently dense to explain the poor visual acuity. Both optic disks appeared slightly atrophic. Neurologic and general medical examinations showed no abnormalities, He appeared to be well nourished. Cranial and orbital computed tomography with contrast, and cranial magnetic resonance imaging without gadolinium showed only generalized cortical atrophy of the cerebral hemispheres. In both eyes the pattern visual-evoked response P100 latencies were abnormal (126 milliseconds). Results of a complete blood cell count, urinalysis, routine blood chemistries, Schilling test, and a serologic test for syphilis were normal, as were the erythrocyte sedimentation rate, serum folate, and vita-
86
AMERICAN JOURNAL OF OPHTHALMOLOGY
July, 1993
Fig. 2 (Rizzo and Lessell). Case 2. Goldmann visual field with III 4e and I4e stimuli. The scotomas are to the Ize stimulus.
min B12 levels. Anti-intrinsic factor antibody was not detected. Weekly injections of 1,000 ~g of hydroxocobalamin were started. Within several weeks the patient noticed improved visual acuity despite his usual consumption of alcohol and tobacco. Three months after the injections were begun, his visual acuity was R.E.: 20/25 and L.E.: 20/30. He could see several Ishihara test plates with each eye and his visual fields were improved. When most recently examined in May 1992, he had a relative paracentral scotoma in the right eye and a normal visual field in the left eye. Visual acuity had declined to 20/30 in each eye from an epiretinal membrane in the right eye and a cataract in the left eye. He never modified his smoking or drinking habits.
Discussion
To a great extent, neuro-ophthalmology has become the specialty that evaluates neurogenic visual loss in patients with neuroimaging studies that disclose no abnormalities. Tobacco amblyopia is one of the diagnoses that is occasionally invoked by referring physicians in such cases, but the final diagnosis is nearly always something else. The patients described in our study represented the only two convincing ex-
amples of tobacco amblyopia seen at the Massachusetts Eye and Ear Infirmary between 1984 and 1992. For the most part, at initial examination our patients had characteristic features of tobacco amblyopia, which is a disease of middle-aged and elderly men who smoke pipes or cigars. Both eyes are affected, although not always symmetrically, by painless, progressive loss of vision with centrocecal scotomas and dyschromatopsia. Recovery of vision can follow cessation of smoking, as in our first patient, or can occur with hydroxocobalamin therapy despite undiminished smoking as in our second patient. The rapidity with which they responded was remarkable. Some experts who doubt that smoking is responsible for this disease indict malnutrition instead.v" Malnutrition would not seem a likely explanation for the loss of vision in our patients. A careful nutritional history indicated that they regularly ate well and both of them looked well nourished. They were also free of neurologic or hematologic stigmata of nutritional deficiency. The pathogenesis of tobacco amblyopia has yet to be elucidated. Nicotine does not appear to have a role and the correlation between the type or amount of tobacco consumed and the occurrence of visual loss is imperfect. Because even in the most prevalent period of the dis-
Vol. 116, No.1
Tobacco Amblyopia
ease, tobacco amblyopia affected only a miniscule percentage of smokers, a multifactorial pathogenesis has been postulated. A multifactorial pathogenesis might also explain why the disease typically appears only after many years of smoking, as it did in our patients. Alcohol consumption has received considerable attention as an etiologic cofactor. The disorder is even designated tobacco-alcohol amblyopia by many current investigators. Certainly, many heavy smokers also use alcohol to excess. However, there is no convincing evidence that ethyl alcohol is toxic to the anterior visual pathway, and several large reviews have documented the occurrence of the disease in smokers who were temperate. Our first patient was abstemious when his vision became impaired and the second recovered his vision despite failure to curb his drinking. Disordered vitamin B12 metabolism has also been suspected in the origin of tobacco amblyopiaY Patients with pernicious anemia may develop an optic neuropathy, sometimes as the herald symptom of the disease." In other B12 deficiency states, such as diphyllobothriasis, patients are predisposed to an optic neuropathy and smoking may be an additional risk factor in these individuals.'? There is also evidence that smoking impairs the absorption of vitamin B12 in patients with tobacco amblyopia." However, most patients with tobacco amblyopia have vitamin B12 levels well within the normal range, as was true in both of our patients. The second patient also had normal results of a Schilling test and had no anti-intrinsic factor antibodies. Whereas earlier methods to quantitate vitamin B12 levels were inexact because of their tendency to report spuriously increased levels, the current standard uses intrinsic factor as the binding agent and has high specificity for B12 • For these reasons and the lack of neurologic signs of subacute combined degeneration (peripheral neuropathy, mental status changes, and deficits in proprioception) that result from vitamin B12 deficiency, there is no reason to believe that disordered vitamin B12 metabolism had a role in causing their optic neuropathy. The absence of anemia cannot be used to exclude a diagnosis of B12 deficiency because this association depends on other factors, such as iron levels, and is therefore unreliable. Recognition of tobacco amblyopia partially depends on discovering a centrocecal scotoma,
87
which is an unusual but nonspecific clinical sign. Centrocecal scotomas may be found in patients who have optic neuritis, nutritional optic neuropathy, Leber's hereditary optic neuropathy, cilioretinal artery occlusion, and toxic and sundry other optic neuropathies. Centrocecal scotomas are easiest to recognize with a tangent screen or Goldmann perimeter, although automated visual fields can be helpful especially if directed or customized for the central region. Bilateral visual loss consequent to smoking (tobacco amblyopia), although rare, is still encountered. As illustrated by our two patients with the disorder, malnutrition, alcoholism, or disordered vitamin B12 metabolism need not be present. Cessation of smoking or treatment with hydroxocobalamin can effect recovery.
References 1. Samples, J. R., and Younge, B. R.: Tobacco-alcohol amblyopia. J. Clin. Neuro. Ophthalmol. 1:213, 1981. 2. Potts, A. M.: Tobacco amblyopia. Surv. Ophthalmol. 17:313, 1973. 3. Mackenzie, W.: A Practical Treatise on Diseases of the Eye, ed. 4. London, England, Longman, Brown, Green, and Longmans, 1854, p. 1067. 4. Traquair, H. M.: Tobacco amblyopia. Lancet 2:1173,1928. 5. - - : Toxic amblyopia, including retrobulbar neuritis. Trans. Ophthalmol. Soc. U. K. 50:351,1930. 6. Dreyfus, P. M.: What is the cause of tobaccoalcohol amblyopia? In Brockhurst, R. J., Boruchoff, S. A., Hutchinson, B.T., and Lessell, S.: Controversy In Ophthalmology. Philadelphia, W. B. Saunders, 1977, pp. 844-850. 7. Victor, M.: Tobacco amblyopia, cyanide poisoning and vitamin Bl2 deficiency. In Smith, J. L.: Neuroophthalmology. Hallandale, Florida, Huffman, 1970, pp.33-48. 8. Heaton, J. M., McCormick, A. J. A., and Freeman, A. G.: Tobaccoamblyopia. A clinical manifestation of vitamin B12 deficiency. Lancet 2:286, 1958. 9. Cohen, H.: Optic atrophy as a presenting sign in pernicious anemia. Lancet 2:1202, 1936. 10. Bjorkenheim, B.: Optic neuropathy caused by vitamin B12 deficiency in carriers of the fish tapeworm, diphyllobothrium latum. Lancet 1:688, 1966. 11. Watson-Williams, E. J., Bottomley, A. c.. Ainley, R. G., and Philips, C. 1.: Absorption of vitamin B12 in tobacco amblyopia. Br. J. Ophthalmol. 53:549, 1969.