Tobacco optic neuropathy (TON) the historical ... - Wiley Online Library

Acta Ophthalmologica 2011

Historical Article

Tobacco optic neuropathy (TON) – the historical and present concept of the disease Andrzej Grzybowski1 and Graham E. Holder2 1

Department of Ophthalmology, Poznan City Hospital, Poland Consultant Electrophysiologist, Director of Electrophysiology, Moorfields Eye Hospital, Honorary Professor Institute of Ophthalmology, University College London, UK 2

ABSTRACT. This article reviews the historical and current concepts of ‘tobacco optic neuropathy’ (TON) a rare disorder of optic nerve function related to the toxic effects of an unidentified constituent of tobacco. It is considered to be an entity distinct from that often described as ‘tobacco-alcohol amblyopia’, a disorder better described as a nutritional optic neuropathy. It is suggested that ‘tobacco-alcohol amblyopia’ is an inappropriate term, because the condition to which it refers is not an amblyopia, and there is little evidence to implicate a toxic effect of either tobacco or alcohol in the pathogenesis of that disorder.

Acta Ophthalmol. 2011: 89: 495–499 ª 2010 The Authors Journal compilation ª 2010 Acta Ophthalmol

doi: 10.1111/j.1755-3768.2009.01853.x

Introduction This article addresses the historical and clinical aspects of tobacco optic neuropathy (TON). This disorder is distinct from that usually known as ‘tobacco-alcohol optic neuropathy’ which is more appropriately described as a nutritional optic neuropathy.

The beginning of tobacco use in Europe It is widely accepted that Christopher Columbus was the first person outside the Americas to encounter tobacco leaves. In 1492, Columbus wrote ‘I saw a man carrying dried leaves which are in high value among them, for a

quantity of it was brought to me at San Salvador’ (Grzybowski 2005). The earliest reference to tobacco smoking is found in the first volume of Gonzalo Fernandez de Orviedo monumental work La Historia general de las Indias (Seville, 1535) about the discovery of the Americas (Grzybowski 2005). He commented on the practice of cultic tobacco smoking by shamans and the methods of tobacco cultivation among Caquetio Indians of Northern Venezuela. Girolamo Benzoni confirmed during his travels from 1541 to 1555 that the shamans of Hispaniola and certain Central American provinces ‘poisoned themselves’ with tobacco smoke during a curing seánce. Other explorers wit-

nessed cigar smoking on the coast of Brazil. In 1555, the Franciscan friar Andre Thevet made contact with the Tupinamba Indians in Brazil and reported on their use of cigars to suppress hunger and thirst (Grzybowski 2005). The propagation of tobacco in Europe in the 16th century was mainly because of two people, Jean Nicot de Villemain in France and Sir Walter Raleigh in England. Jean Nicot was French ambassador to the Portuguese court from 1559 to 1561 and sent some powdered tobacco leaves to the Queen Mother Catherine de Medici, recommending it for her severe headaches. Reportedly, the remedy worked and the tobacco plant quickly gained popularity in France. The plant came to be called the Herb of Nicot (Grzybowski 2005). Even though Raleigh is often credited with being the first Englishman to discover tobacco, Sir John Hawkins and his crew are thought to have smoked tobacco much earlier, in 1564. It is known that over the next twenty years many English sailors smoked tobacco, including the crews of ships captained by Sir Francis Drake. In 1586, Raleigh sailed for the Americas and met Ralph Lane, the first Governor of Virginia, who is believed to have taught Raleigh to smoke a clay pipe. In the following year, some of the Virginia colonists returned to England and introduced tobacco into English

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society. In 1595, the first book on the subject, ‘Tobacco’, was published. However, Raleigh did much for the propagation of tobacco in England, persuading Elisabeth I to try smoking in 1600 and making tobacco fashionable after he smoked at the execution of the Earl of Essex in 1601 (Benedict 2005).

Tobacco and vision The first article describing harmful effects of tobacco was the anonymous ‘Work for Chimney sweepers – a warning for tobacconists’ (1602), but it did not address the relationship between tobacco and vision (Dunphy 1969). The first non-medical article to report tobacco-related problems for vision was the treatise by King James I of England (1604) entitled ‘Counter Blast against tobacco’. Later authors disagreed. Some, like Dr. William Barclay, in his work ‘Nepenthes or the Vertues of Tobacco’ advocated in 1614 the beneficial influence of tobacco on sight. Others, e.g., Dr. William Vaughn in ‘Directions for health’ from 1617, pointed its deleterious effects on the eye (Dunphy 1969). The potential toxicity of tobacco on vision was elaborated by Dr. Tobias Venner in ‘Via Recta ad Vitam Longam’ in 1650. This work was discussed extensively by Pearl and Usher (Pearl 1932; Usher 1927).

Tobacco optic neuropathy The first relatively modern report of tobacco optic neuropathy was by Joseph Beer, an early European ophthalmologist, entitled ‘Lehre der Augenkrankheiten’ (1792) (Dunphy 1969). The disorder appeared in the textbook of ophthalmology by William Mackenzie, co-founder of the Glasgow Eye Infirmary, in his ‘Treatise on Diseases of the Eye’ (1833) (Usher 1927). John Lizars, Senior Operating Surgeon at the Royal Infirmary of Edinburgh, Scotland, in his book ‘The use and abuse of tobacco’ (1859) described vision deterioration and amaurosis as common consequences of smoking tobacco (6). Hutchinson (1863) and Michel (1865) were other ophthalmologists to describe tobacco optic neuropathy, as did Hughlings Jackson

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(1865) in his article ‘The effects of tobacco smoking and diseases of the nervous system’ (Arrington 1959). Charles Drysdale in his book ‘Tobacco and the diseases it produces’ Drysdale (1875) reported his experiences with tobacco ‘poisoning’ in the following words: ‘one of the symptoms produced in acute poisoning by tobacco is blindness; and chronic poisoning gives rise to similar symptoms. Mackenzie of Glasgow first noticed that male patients affected with one species of amaurosis were mostly great lovers of tobacco in some form. (...) In one week I saw, in 1874, at the Royal London Ophthalmic Hospital, two cases of tobacco amaurosis in young men, neither of whom had attained the age of thirty. The first had chewed continually, and the other smoked the enormous quantity of one ounce of shag tobacco daily. Both were completely and irretrievably blind (…). But weak sight is also commonly caused by snuffing, as well as by smoking and chewing‘ (8). Tobacco as a cause of ‘the pupils dilation, vision deterioration, appearance of bright lines and dotes and extended sensation of retinal perception’ was described by John Hinds, Professor of Chemistry, Cumberland University, Lebanon, TN, USA, in his book ‘The use of tobacco (1882)’ (Hinds 1882). The significance of tobacco optic neuropathy was also reported in the French medical literature by Michel in 1865 (Michel 1865). Many subsequent publications appeared in the late 19th and early 20th centuries with hundreds of cases noted. Although many authors, for example Nettleship (1887), Eales (1887) and Gunn (1887) implicated only tobacco in the pathogenesis of the disorder, others, such as DeSchweinitz (1896), did not differentiate between alcohol and tobacco toxicity. DeSchweinitz was the first also to propose a contribution of nutritional deficiency to the pathogenesis of the disorder. At the same time, several original and review articles on the subject appeared, including the work of Traquair with extensive studies on visual field changes in tobacco optic neuropathy (Traquair 1927, 1928, 1931). Abel Gy in his book ‘L’Intoxication par le tabac’ (1913) reviewed the literature describing the toxic effect of tobacco on the visual system, emphasising the role of toxic tobacco optic

neuropathy in the articles by Nettleship, Hirschberg, Langley and Anderson, Terson and Terrien (Gy 1913). Gypointed out the similarities between the toxicity of alcohol and tobacco on the optic nerve. He cited the work of Gae˛zowski, who had found 21 cases of pure tobacco toxicity in 158 patients with the deterioration of vision; in another article, Gae˛zowski described 151 cases of mixed alcohol-tobacco optic neuropathy. Fieuzal found 104 cases of tobacco optic neuropathy. The pathogenesis of the disorder remained unclear. In the second half of the 20th century, several articles were published critically analysing the literature of the previous 150 years and the nature of tobacco optic neuropathy. From 1817 to 1966, several thousand cases were described, but the occurrence of the disorder had considerably reduced in modern times (Nettleship 1887; Eales 1887; Gunn 1887; DeSchweinitz 1896; Traquair 1927, 1928, 1931; Rizzo & Lessell 1993). In the 19th century, it appeared relatively common (Mackenzie related that he met such cases daily) (19). At the beginning of the 20th century, it was estimated as occurring in 1% of the general population (it was even compared to glaucoma and retinal detachment) (Dunphy 1969; Traquair 1928). Currently, it is rare (Fig. 1) (Rizzo & Lessell 1993; Samples & Younge 1981); one of the authors in an extensive practice has seen only two cases with a secure diagnosis. Silvette et al. (1960) in an extensive review article (financed by tobacco companies) pointed out that among 935 cases of that disorder described in the medical literature in the years 1861–1960, 50% originated in the years 1871–1890. Moreover, in the same article it was calculated that the incidence of tobacco-alcohol optic neuropathy was 0.85% of the total population of nearly 290 000 eye patients, and for pure tobacco optic neuropathy )0.77% of the total population of nearly 300 000 patients with eye disease. Uthoff in his review article in 1911 collected 403 articles concerning the influence of tobacco and alcohol on the eye (Silvette et al. 1960). By the end of the 20th century, a paradox had become apparent; despite an increased use of tobacco products


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in the general population (Fig. 2), there was a marked decrease in the incidence of tobacco optic neuropathy. One possibility is that a number of early cases were probably misdiagnosed. For example, it was shown that some patients diagnosed as tobacco optic neuropathy carried a genetic mutation characteristic for Leber’s hereditary optic neuropathy (LHON) (Cullom et al. 1993; Mackey & Howell 1994; Johns et al. 1993). Secondly, the nutritional status of the general population, which may have contributed to the development of optic neuropathy in Victorian times, is at present of minor importance, at least in the devel-

oped world. Further, the very low current incidence suggests that the most common current form of tobacco consumption, cigarette smoking, may not precipitate the disorder.

Clinical picture of TON TON usually presents in elderly pipesmoking men. There is a bilateral relative centro-caecal field defect, more marked for a red or green target than white, and a characteristic disturbance of colour discrimination on the Farnsworth-Munsell 100 Hue Test (Foulds et al. 1974). Vision can

improve to normal or near normal over a period of 3-12 months if they stop smoking (Foulds et al. 1974; Harrington 1962). The visual field changes were postulated as the most characteristic clinical findings in TON (Traquair 1927, 1928, 1931; Harrington 1962). Rucker proposed in 1946 that ‘about half a dozen cigars a day or a couple of ounces of pipe tobacco a week, smoked for a number of years seem necessary to produce this type of amblyopia’ and that ‘cigarette smoking alone does not cause it’ (Rucker 1946). Harrington argued that it occurred most commonly in pipe smokers, cigar smokers, users of chewing tobacco and users of snuff, in that order of frequency (Harrington 1962), and this was confirmed in later reports (Rizzo & Lessell 1993; Samples & Younge 1981). Nicotine may not play a role in the pathogenesis of the disorder. It was proposed that smoking, especially in genetically susceptible patients, might affect sulphur metabolism, leading to chronic cyanide intoxication (Freeman 1988) and the deficiency of vitamin B12 (Wokes 1958; Heaton et al. 1958). There are several reports confirming the co-existence of tobacco toxicity with deficiency of hydroxycobalamin (Wokes 1958; Heaton et al. 1958). On the other hand, most patients with TON have B12 levels within the normal range (Silvette et al. 1960). It was proposed that genetic susceptibility overlaps with toxic environmental influences (Johns et al. 1993). Tobacco abstinence, and oral and intramuscular B vitamins, particularly vitamin B1 and B12, were proposed as appropriate therapy (Younge 1996). In the 1976 report of the Center for Disease Control based on all the medical and epidemiological data on the toxicity of tobacco from 1964 to 1975, tobacco amblyopia was defined as ‘a syndrome of visual failure occurring in association with the use of tobacco, with or without the concurrent use of alcohol, and with or not concurrent nutritional deficits’. In the summary of the report it was stated that ‘tobacco amblyopia is presently a rare disorder in the United States. The evidence suggests that this disorder is related to nutritional or idiopathic deficiencies in certain detoxification mechanisms, particularly in

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handling the cyanide component of tobacco smoke’ (Holman 1976).

‘Tobacco – alcohol amblyopia’ What is the precipitating factor? As most heavy drinkers were also smokers, for many years, it was difficult to differentiate these two factors, and the term ‘tobacco-alcohol amblyopia’ was commonly used. As early as the end of the 19th century, there were ophthalmologists, including Nettleship, Eales, Gunn, Hirschberg and DeSchweinitz, who believed that tobacco alone was the culprit (Dunphy 1969). Hutchinson even proposed that alcohol was antagonistic to tobacco and in small amounts was beneficial. (Hutchinson 1863) Other prominent ophthalmologists of that time, including Fuchs and Jackson, insisted that the disease was caused by a combination of two poisons (Dunphy 1969). It now seems possible that there are two distinct disorders – tobacco optic neuropathy (TON) and nutritional optic neuropathy related to alcohol over consumption.

remains free from amblyopia as long as he does not acquire a gastric catarrh or anorexia’ (Horner 1878). DeSchweinitz in 1896 wrote that ‘other circumstances (besides alcohol) which favour a deleterious effect of tobacco on vision are malnutrition from any source, chronic gastritis, dyspepsia, mental worry, and particularly insomnia’ (DeSchweinitz 1896). However, a partial breakthrough was made by Calhoun, who in 1918 noted centrocecal and central scotomata in the visual fields of pellagra patients, and establishing that such field defects could arise on a nutritional basis (Dunphy 1969). The typical picture of optic neuropathy in undernourished people was observed by Gjessing after World War I (Gjessing 1939) and by Schepens during World War II (Schepens 1946). Carroll provided what appears to be the conclusive evidence (Carroll 1935, 1947, 1966), he showed that patients with ‘tobacco-alcohol’ optic neuropathy partially or completely recovered their vision following vitamin B supplementation despite continuing their usual intake of alcohol and tobacco (Carroll 1966).

Conclusion Nutritional optic neuropathy (NON) instead of alcohol amblyopia Horner was one of the first to propose the role of nutritional deficit in provoking optic neuropathy. He argued that ‘the strongest smoker and drinker

tal optic neuropathies, mainly LHON. The disorder appeared common (even allowing for possible misdiagnoses) in the 19th and first half of the 20th centuries, and the change in tobacco intake habits – in the past snuffing and chewing dominated, currently mostly cigarette smoking (Fig. 3) – is probably a significant factor in its current rarity. An additional contributory factor is that nutritional deficiencies were more frequent 100–150 years ago. It is worth mentioning that a test for syphilis would not become available until the turn-of-the century, ischaemic optic neuropathy would not be discovered until the mid 20th century and demyelinative optic neuritis was just becoming recognised. It seems probably that alcohol (ethyl alcohol) and ‘tobacco-alcohol’ optic neuropathy are in fact nutritional optic neuropathy. The term ‘tobaccoalcohol amblyopia’ is misleading. There is neither amblyopia nor any proven interaction between alcohol and tobacco in the pathogenesis of the disorder and use of the more accurate term, nutritional optic neuropathy, is recommended.

Acknowledgement

TON is a rare, distinct clinical entity. It seems to occur in tobacco users who are not cigarette smokers. As the clinical picture is not definitive, the diagnosis should be made after the exclusion of the much more common nutritional optic neuropathy, other toxic optic neuropathies and congeni-

Authors would like to thank Simmons Lessell, M.D., Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Boston, USA, for his review of the manuscript and helpful suggestions.

References 100

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Arrington GE (1959): A history of ophthalmology. New York: MD Publications Inc. Benedict C (2005): Therapeutic uses. In: Goodman J (ed) Tobacco in History and Culture, An Encyklopedia. Detroit: Charles Scribner’s Sons 609–615. Carroll FD (1935): Analysis of 55 cases of tobacco-alcohol amblyopia. Arch Ophthalmol 14: 421–434. Carroll FD (1947): Nutritional retrobulbar neuritis. Am J Ophthalmol 30: 172–176. Carroll FD (1966): Nutritional amblyopia. Arch Ophthal 76: 406–411. Cullom ME, Heher KL, Miller NR, Savino PJ & Johns DR (1993): Leber’s hereditary optic neuropathy masquarading as tobaccoalcohol amblyopia. Arch Ophthalmol 111: 1482–1485. DeSchweinitz GE (1896): Toxic amblyopias. Philadelphia: Lea Brothers and Co.


Drysdale C (1875): Tobacco and the diseases it produces. London: Bailliere, Tindall, and Cox. Dunphy EB (1969): Alcohol and tobacco amblyopia: a historical survey. Am J Ophthamol 68: 569–578. Eales H (1887): Toxic amblyopia. Trans Ophthalmol Soc U K 7: 54–61. Foulds WS, Chrissholm IA & Pettigrew AR (1974): The toxic optic neuropathies. Br J Ophthalmol 58: 386–390. Freeman AG (1988): Optic neuropathy and chronic cyanide intoxication: a review. J R Soc Med 81: 103–106. Gjessing H (1939): Discussion: tobacco amblyopia. Trans Ophthal Soc U K 59: 249–254. Grzybowski A (2005): Historia zainteresowania tytoniem i nikotynizmem do poowy XX wieku w Europie [The history of tobacco consumption and nicotine addiction in Europe until the middle of the XXth century]. Przegl Lek 62: 1211– 1214. Gunn M (1887): Toxic amblyopia. Trans Ophthalmol Soc U K 7: 67–71. Gy A (1913): L’Intoxication par le tabac. Paris: Masson et Cie. Harrington DO (1962): Amblyopia due to tobacco, alcohol and nutritional deficiency. Am J Ophthalmol 53: 967–972. Heaton JM, McCormick AJA & Freeman AG (1958): Tobacco amblyopia: a clinical manifestation of vitamin B12 deficiency. Lancet 2:286–290. Hinds J (1882): The use of tobacco. Nashville: Cumberland Presbyterian Publishing House.

Holman PB (ed.). (1976): Tobacco amblyopia. In: The health consequences of smoking: a reference edition. Atlanta, GA: Center for Disease Control 527–534. Horner JF (1878): Ueber Intoxicationsamblyopie. Correspondenzblatt fu¨r Schweizer Aerzte 8: 396–399. Hutchinson J (1863): Clinical data respecting amaurosis, more especially respecting that form of it supposed to be induced by tobacco. Lancet 2: 536–538. Johns DR, Heher KL, Miller NR & Smith KH (1993): Leber’s hereditary optic neuropathy. Clinical manifestations of the 14484 mutation. Arch Ophthalmol 111: 495–498. Lizars J (1883): The use and abuse of tobacco, 1859, reprintem. Philadelphia: P. Blakiston, Son and Co. Mackey D & Howell N (1994): Tobacco amblyopia. Am J Ophthalmol 117: 817–818. Michel J (1865): Nouvelles recherches pratiques sur l’amblyopie et l’amaurose causees par l’abus du tabac a fumer, avec des remarques sur l’amblyopie et l’amaurose des buveurs. Ann Ocul (Paris) 54: 122–124. Nettleship E (1887): Toxic amblyopia. Trans Ophthalmol Soc U K 7: 36–53. Pearl R (1932): Quotations: tobias venner and his via recta. Hum Biol 4: 558–568. Rizzo JF & Lessell S (1993): Tobacco amblyopia. Am J Ophthamol 116: 84–87. Rucker CW (1946): The interpretation of visual fields. Home Study Course Manual. Am Acad Ophthalmol, 24–25. Samples JR & Younge BR (1981): Tobaccoalcohol amblyopia. J Clin Neuroophthalmol 1: 213–218.

Schepens CL (1946): Is tobacco amblyopia a deficiency disease? Trans Ophth Soc UK 66: 309–331. Silvette H, Haag HB & Larson PS (1960): Tobacco amblyopia. The evolution and natural history of a ‘‘tobaccogenic’’ disease. Am J Ophthalmol 50: 71–100. Traquair HM (1927): An introduction to clinical perimetry. St Louis: The C.V. Mosby Company. Traquair HM (1928): Tobacco amblyopia. Lancet 2: 1173–1177. Traquair HM (1931): Toxic amblyopia. Trans Ophthalmol Soc U K 50: 372–385. Usher CH (1927): An Analysis of the Consumption of Tobacco and Alcohol in Cases of Tobacco Amblyopia. Ann Eugen 2: 245–248. Wokes F (1958): Tobacco amblyopia. Lancet 2: 526. Younge BR (1996): Toxic and Nutritional Optic neuropathy. In: Kline L (ed) Optic nerve disorders. San Francisco: American Academy of Ophthalmology 163–177.

Received on August 12th, 2009. Accepted on December 11th, 2009. Correspondence: Andrzej Grzybowski, MD, PhD Department of Ophthalmology Poznan City Hospital ul. Szwajcarska 3 61-285 Poznan´ Poland Email: [email protected]

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