TABLE 2. Methods used in retrospective and cross sectionat studies of peptic ulcer and smoking (cont.) Author, Year. country. reference Sex Number Method of selection Number Contlnls Method of selection Comme"ts Kasanen and M ForsstrSm. 1966. Finland (18). 43 Gastric. Successive male admissions with pep- 100 Successive men treated at medical A special questionnaire 67 Duodenal. tic ulcer treated at medical clinic clinic who had no gastrointestinal wes used for the or outpatient department of Uni- symptoms or signs of CHD. interview. versity Hospital. Only patients under 66 years of age or those who had been working were in- cluded. Gillies and Skyring. 1968, 196R. Australia (9). M and F 100 Gastric. Patients with peptic ulcer were se- 150 Matched by age and sex from the Diagnosis well established 60 Duodenal. lected from hospital admissions in seme ward at the same time and with X-ray, gastros- 1967. with absence of signs or symp- copy. or surgery. toms or past history of upper gastrointestinal disease. Gillies and M and F 10 Gastric. 1,405 workers from a broadcasting 100 Two control groups: All information obtained Skyring. 48 Duodenal. company, a manufacturing corn- 1. 100 peptic ulcer patients we- by question card. All 1969, 1R Uncertain peny, and a bus company were viously reported by authors. ulcers were proved by Australia location. interviewed for a history of pep- 1,329 2. 1.329 workers without ulcer. X-ray or surgery. (IO). tic ulcer. Monson. M and F 62 Gastric. 643 physicians fmm Massachusetts 625 Controls were physicians without Diagnosis established by 1970. 462 Duodenal. who responded a5irmatively to I) ulcer disease who were matched X-ray or SUrgelY except U.S.A. (15). 139 Not questionnaire sent to them in 1967 to ulcer patients by year of birth. for 46 "clinical" cases. specified. asking how many had had LL pep- tic ueer. TABLE 3.-Summary of results of retrospective and cross sectional studies of peptic ulcer and smoking Author, ye*c co""trY. reference Barnett, 1927, U.S.A. (2). Percent nonsmoker ChS.33 controls Total . . 18.0 26.0 Gastric . . . . 16.0 Duodenal . . . 20.0 Amount of tobacco used C*WS Co"trols Trowel& 1934. England (91). Duodenal 8.0 17.0 Average number: Cigarettes 12.0 per day. .ll.l per day Pipe 1.6 ounces per week. 2.16 ounces per week Allibone and Flint, 1958. England (1). 38.0 64.0 Doll et sl., 1968. Englend (7). Gastric: Males . 1.3 Females . 61.1 Duodenal: Males 2.1 Females 53.7 4.7 66.8 5.8 62.0 Gastric: Percent emoking >25 cigarette8 per day Males . . 10.6 11.3 Females 1.1 1.1 Duodenal: Males ._ ._ 10.2 12.1 Females 1.9 1.9 Edwards Percent of peptic ulcer bu et al.. smoking category 1959, Never smoked . . . . . . . 6.0 England Formerly smoked . . . . . . . . . . *..* 6.7 (8). Cigarettes: l-9 per day _. _. . 9.4 lo-19 per day _. . . . . . . 9.3 >?Operday . . . 12.0 Pipe . . . . . . . . . . . . . . . . . . . . . 6.6 e Pipe end cigarettes . . . . . . . 8.5 v TABLE 3.-Summary of results of retrospective and cross sectional studies of peptic ulcer and smoking (cont.) Author, year, Percent nonsmoker eountrY. ~ reference Cases Co"trols "Peptic" . . 10.0 40.0 Kasanen end ForsstrSm. 1966, Finland (IS). Amount of tobarco used ~-. Cases Co"trols Cigarettes per dsy: 20 . 19.0 10.0 Gillies end Skyring, 1968. Australia (9). Gastric 18.0 44.0 Duodenal 62.0 71.0 Mean number cigarettes per day: Gastric . 23.3 Duodenal 23.2 Duration of smoking (years) : Gastric 30.2 Duodenal 24.2 17.1 23.0 28.0 28.2 Gillies end Skyring, 1969. Australia (10). Gastric ........ 17.9 55.6 Duodenal ...... 36.6 Monson. 1910. U.S.A. (15). Duodenal ...... 32.1 Gastric ........ 19.2 Not Specified . 43.2 46.7 Percent smoking >20 cigarettes per day Age: Gastric DUOlhWl 20 ......... 38.8 21.3 30.1 30 ......... 45,.7 43.0 41.1 45 ......... 60.2 49.6 46.3 60 ......... 64.1 40.4 44.0 REFERENCES (1) ALLIBONE, A., FLINT, F. J. Bronchitis, aspirin, smoking, and other fac- tors in the aetiology of peptic ulcer. Lancet 2: 179-182, July 26, 1958. (2) BARNETT, C. W. Tobacco smoking as a factor in the production of peptic ulcer and gastric neurosis. Boston Medical and Surgical Journal 197(12) : 457459, September 22, 1927. (3) BATTERMAN, R. C , EHRENFELD, I., The influence of smoking upon the management of the peptic ulcer patient. Gastroenterology 12 (4) : 575- 585, April 1949. (4) COOPER, P., KNIGHT, J. B., JR. Effect of cigarette smoking on gastric secretions of patients with duodenal ulcer. New England Journal of Medicine 255(l) : 17-21, July 5, 1956. (5) DOLL, R., HILL, A. B. Mortality in relation to smoking: 10 years' obser- vations of British doctors. Part I. British Medical Journal l(5395) : 1399-1410, May 30, 1964. (6) DOLL, R., HILL, A. B. Mortality in relation to smoking: 10 years' obser- vations of British doctors (concluded). British Medical Journal l(5396) : 1460-1467, June-G, 1964. (7) DOLL, R., JONES, F. A., PYGOTT, F. Effect of smoking on the production and maintenance of gastric and duodenal ulcers. Lancet 1: 657-662, March 29,1958. (8) EDWARDS, F., MCKEOWN, T., WHITFIELD, A. G. W. Association between smoking and disease in men over sixty. Lancet 1: 196-201, January 24, 1959. (9) GILLIES, M., SKYRING, A. Gastric ulcer, duodenal ulcer and gastric car- cinoma: A case-control study of certain social and environmental fac- tors. Medical Journal of Australia 2(25) : 1132-1136, December 21, 1968. (10) GILLIES, M. A., SKYRING, A. Gastric and duodenal ulcer. The association between aspirin ingestion, smoking and family history of ulcer. Medi- cal Journal of Australia 2(6) : 280-285, August 9, 1969. (11) HAMMOND, E. C. Smoking in relation to the death rates of 1 million men and women. IN : Haenszel, W. (Editor). Epidemiological Approaches to the Study of Cancer and Other Chronic Diseases. Bethesda, U.S. Public Health Service, National Cancer Institute Monograph No. 19, January 1966. pp. 12'7-204. (12) KAHN, H. A. The Dorn study of smoking and mortality among U.S. veterans: Report on 8% years of observation. IN: Haenszel, W. (Edi- tor). Epidemiological Approaches to the Study of Cancer and Other Chronic Diseases. Bethesda, U.S. Public Health Service, National Cancer Institute Monograph No. 19, January 1966. pp. 1-125. (IS) KASANEN, A., FORSSTROM, J. Social stress and living habits in the etiology of peptic ulcer. Annales Medicinae Internal Fenniae 55(l) : 13-22, 1966. (14) MITTY, W. F., JR., ROUSSELOT, L. M., DELANY, G. J. Smoking and its relation to nutritional status of patients following gastrectomy; a five-year follow-up survey of 171 patients. Annals of Surgery 150 (1) : 76-84, July 1959. (15) MONSON, R. R. Cigarette smoking and body form in peptic ulcer. Gastro- enterology 58 (3) : 337-344, March 1970. 429 (16) PACKARD, R. S. Smoking and the alimentary tract: A review. Gut 1: 171-174, 1960. (17) PALMER, W. L. Peptic ulcer. Chapter 32. IN: Paulson, M. (Editor). Gastroenterologic Medicine. Philadelphia, Lea & Febiger, 1969, pp. 710-757. (16) SCHNEDORF, J. G., Iw, A. C. The effect of tobacco smoking on the alimentary tract. An experimental study of man and animals. Journal of the American Medical Association 112(10) : 898-904, March 11, 1939. (19) STEIGMANN, F., DOLEHIDE, R. H., KAMINSKI, L. Effects of tobacco smok- ing on gastric acidity and motility of hospital controls and patients with peptic ulcer. American Journal of Gastroenterology 22 : 399-409, 1954. (20) THOMPSON, J. H. Effects of nicotine and tobacco smoke on gastric secre- tion in rats with gastric fistulas. American Journal of Digestive Diseases 15(3) : 209-217, March 1970. (21) TROUTELL, 0. A. The relation of tobacco smoking to the incidence of chronic duodenal ulcer. Lancet 1: 808-809, April 14,1934. (12) U.S. PUBLIC HEALTH SERVICE. NATIONAL CENTER FOR HEALTH STATIS- TICS. Vital Statistics of the United States-1967. Vol. II-Mortality, Part A. Washington, U.S. Department of Health, Education and Wel- fare, Public Health Service Publication, 1969. (28) WEIR, J. M., DUNN, J. E., JR. Smoking and mortality: A prospective study. Cancer 25( 1) : 105-112, January 1970. 430 CHAPTER 7 Tobacco Amblyopia Contents Summary and conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 433 TOBACCO AMBLYOPIA Tobacco amblyopia (tobacco-alcohol amblyopia) is that syn- drome of visual failure occurring in association with the use of tobacco, with or without the concurrent use of alcohol, and with or without concurrent nutritional deficits. The disease has a subacute onset, leading to a loss of visual acuity and color perception (12). It is characterized by centrocecal scotomas which are bilateral but not necessarily symmetrical and which have sloping diffuse edges and by the presence of nuclei of denser visual loss within the large scotomas (22,23). Such visual impairment is not unique to tobacco amblyopia, as it is also seen in neurodegenerative disorders, such as Leber's hereditary optic atrophy (7,25). Clinical information on tobacco amblyopia has appeared in nu- merous articles throughout the past century. This information has been reviewed by Silvette, et al. (17) and, more recently, by Dunphy (5). Pure tobacco amblyopia (TA) , that is amblyopia unassociated with excessive alcohol intake or the exposure to other toxins, is rarely seen in the United States today (12). Walsh, et al. (23) have observed that when TA is found it is usually present in association with nutritional or idiopathic vitamin deficiencies. Victor (22) recently observed that the type of visual defect seen in tobacco amblyopia may be found in clinical circumstances in which tobacco is clearly not a causative factor. He questions whether TA is distinguishable from other forms of amblyopia. The prevalence of this disorder has been variously estimated in the past at from 0.5 to 1.5 percent of all eye clinic patients (20,23). However, currently in the United States, it appears to be a rare condition. Silvette, et al. (17) have observed that the incidence of tobacco amblyopia appears to have decreased substantially during the past decades. Other authors (3, 15) have also commented on this trend. Although reference has been made to the increased fre- quency of certain types of tobacco usage in patients with this dis- order, adequate population studies with proper controls have yet to be performed. The association of this disorder with the use of tobacco is strengthened by the frequent clinical observations of improvement following the cessation of smoking although improve- ment has been noted by some to occur without cessation. Research into the pathogenesis of tobacco amblyopia has cen- 435 tered upon the interrelationships of cyanide metabolism, vitamin B,,, and other vitamin deficiencies. Three reviews of this material have recently appeared (1, 12, 2.2). Numerous studies reviewed in these articles suggest that tobacco amblyopia may result from the incomplete detoxification of the cyanide present in tobacco smoke. This failure of detoxification may stem from or be intensified by inadequate dietary intake of necessary nutritional factors. This may be the reason for the association of this disorder with exces- sive alcohol intake and with its related nutritional deficits (2, 4, 6, 8,9,10,11,13,14,16,18, 19,21,24,26,27,28). SUMMARY AND CONCLUSIONS Tobacco amblyopia is presently a rare disorder in the United States. The evidence suggests that this disorder is related to nutri- tional or idiopathic deficiencies in certain detoxification mechan- isms, particularly in handling the cyanide component of tobacco smoke. REFERENCES (1) CANADIAN MEDICAL ASSOCIATION JOURNAL. Tobacco amblyopia. (Edi- torial) Canadian Medical Association Journal 102(4) : 420, February 28, 1970. (2) CHISHOLM, I. A., BRONTE-STEWART, J., FOULDS, W. S. Hydroxocobalamin versus cyanocobalamin in the treatment of tobacco amblyopia. Lancet 2(7513) : 450-451, August 26, 1967. (5) DARBY, P. W., WILSON, J. Cyanide, smoking, and tobacco amblyopia. Observations on the cyanide content of tobacco smoke. British Journal of Ophthalmology 51(5) : 336-338, May 1967. (4) DREYFUS, P. M. Blood transketolase levels in tobacco-alcohol amblyopia Archives of Ophthalmology `74(5) : 617-620, November 1965. (5) DUNPHY, E. B. Alcohol and tobacco amblyopia: A historical survey. American Journal of Ophthalmology 68(4) : 569-578, October 1969. (6) FOULDS, W. S., BRONTE-STEWART, J. M., CHISHOLM, I. A. Serum thio- cyanate concentrations in tobacco amblyopia. Nature 218 (5141) : 586, May 11, 1968. (7) FOULDS, W. S., CANT, J. S., CHISHOLM, I. A., BRONTE-STEWART, J., WILSON, J. Hydroxocobalamin in the treatment of Leber's hereditary optic atrophy. Lancet l(7548) : 896-897, April 27, 1968. (8) FOULDS, W. S., CHISHOLM, I. A., BRONTE-STEWART, J., WILSON, T. M. Vitamin B,, absorption in tobacco amblyopia. British Journal of Ophthalmology 53 (6) : 393-397, June 1969. (9) FOULDS, W. S., CHISHOLM, I. A., BRONTE-STEWART, J., WILSON, T. M. The optic neuropathy of pernicious anemia. Archives of Ophthalmol- ogy 82(4) : 427-432, October 1969. (10) FREEMAN, A. G., HEATON, J. M. The aetiology of retrobulbar neuritis in Addisonian pernicious anaemia. Lancet l(7183) : 908-911, April 29, 1961. 436 (11) HEATON, J. M., MCCORMICK, A. J. A., FREEMAN, A. G. Tobacco amblyo- pia : A clinical manifestation of vitamin-B,, deficiency. Lancet 2(7041) : 286-290, August 9, 1958. (12) KNOX, D. L. Neuro-ophthalmology. Archives of Ophthalmology 83(l) : 103-127, January 1970. (13) LINDSTRAND, K., WILSON, J., MATTHEWS, D. M. Chromatography and microbiological assay of vitamin B1? in smokers. British Medical Journal 2 (5520) : 988-990, October 22, 1966. (14) LINNELL, J. C., SMITH, A. D. M., SMITH, C. L., WILSON, J., MATTHEWS, D. M. Effects of smoking on metabolism and excretion of vitamin B,,. British Medical Journal 2(5599) : 215-216, April 27, 1968. (15) SCHEPENS, C. L. Is tobacco amblyopia a deficiency disease- Transactions of the Ophthalmological Society of the United Kingdom 66: 309-331, 1946. (16) SCHIEVELBEIN, H., WERLE, E., SCHULZ, E. K., BAUMEISTER, R. The influ- ence of tobacco smoke and nicotine on thiocyanate metabolism. Naunyn-Schmiedebergs Archiv fiir Pharmakologie und Experimentelle Pathologie 262(3) : 358-365, February 5, 1969. (17) SILVETTE, H., HAAG, H. B., LARSON, P. S. Tobacco amblyopia. The evolu- tion and natural history of a "tobaccogenic" disease. American Journal of Ophthalmology 50( 1) : 71-100, January 1960. (18) SMITH, A. D. M. Retrobulbar neuritis in Addisonian pernicious anae- mia. (Letter) Lancet l(7184) : 1001-1002, May 6, 1961. (19) SMITH, A. D. M., DUCKETT, S. Cyanide, vitamine B,,, experimental demyelination and tobacco amblyopia. British Journal of Experimen- tal Pathology 46(6) : 615-622, December 1965. (20) TRAQUAIR, H. M. Toxic amblyopia, including retrobulbar neuritis. Trans- actions of the Ophthalmological Society of the United Kingdom 50: 351385, 1930. (21) VICTOR, M. Tobacco-alcohol amblyopia. A critique of current concepts of this disorder, with special reference to the role of nutritional deficiency in its causation. Archives of Ophthalmology 70(3) : 313-318, Septem- ber 1963. (22) VICTOR, M. Tobacco amblyopia, cyanide poisoning and vitamin B,, de- ficiency. A critique of current concepts. Chapter 3. IN: Smith, J. L. (Editor) Neuro-Ophthlamology. Symposium of the University of Miami and the Bascom Palmer Eye Institute. Hallandale, Florida, Huffman Publishing Co., 1970. pp. 3348. (2s) WALSH, F. B., HOYT, W. F. (Editors) Neurotoxic substances affecting the visual and ocular motor systems. Chapter 15: IN: Clinical Neuro- Ophthalmology, Volume 3, 3rd Edition. Baltimore, The Williams & Wilkins Company, 1969. pp. 2613-2616. (24) WATSON-WILLIAMS, E. J., BOTTOMLEY, A. C., AINLEY, R. G., PHILLIPS, C. I. Absorption of vitamin B12 in tobacco amblyopia. British Journal of Ophthalmology 53 (8) : 549-552, August 1969. (85) WILSON, J. Leber's hereditary optic atrophy: A possible defect of cya- nide metabolism. Clinical Science 29(3) : 505-515, December 1965. (26) WILSON, J., MATTHEWS, D. M. Metabolic inter-relationships between cyanide, thiocyanate and vitamin B,, in smokers and nonsmokers. Clinical Science 31(l) : l-7, January 1966. 437 (27) WOKES, F., PICARD, C. W. The role of vitamin B,, in human nutrition. Clinical Nutrition 3 (5) : 383-390, September-October 1955. (28) WYNDER, E. L., HOFFMANN, I). Certain constituents of tobacco products. Chapter 8. K. Vapor phase of tobacco smoke. IN: Wynder, E. L., Hoffmann, I). (b:ditors). Tobacco and Tobacco Smoke. Studies in Ex- perimental Carcinogenesis. New York, Academic Press, 1967. pp. 451-453. 43.3