VIII. VITAMIX A DEFICIENCY IX IIITMAX BEINGS 143 



placques (Bitot's spots) on the scleral conjunctiva. Keratomalacia refers to 

 later manifestations of the same processes, involving edema, infiltration, 

 and necrotic softening of the cornea, which may be followed by perforation, 

 hypopyon, and panophthalmitis. 



1. Early Investigations 



These ophthalmic disorders were well recognized by European clinicians 

 for almost 100 years before they became established as symptoms of vita- 

 min A deficiency. During the latter half of the nineteenth century they 

 were reported from all parts of the world, their frequent association with 

 night blindness noted, and the beneficial effect of liver and of cod liver oil 

 recorded. Bitot's^ description (1863) of the placques which bear his name 

 was based upon 29 patients, 9 to 19 years of age, all of whom showed night 

 blindness. As early as 1876, SnelP was successfully treating cases of night 

 blindness with Bitot's spots with cod liver oil and steel (a compound of 

 iron salts) as if that were the generally accepted remedy. 



The first account of the pathologic anatomy of the lesions, emphasizing 

 hyperplasia of the corneoconjunctival mucosa with marked flattening of 

 the superficial epithelium, was presented by Leber^ in 1883. In that same 

 year, de Gouvea^ described a series of cases in plantation slaves in Rio de 

 Janerio, and reported effective treatment with cod liver oil. Macroscopical 

 changes only were emphasized in the classic studies of Mori,^'' based on 

 1511 cases of xerophthalmia and 116 cases of keratomalacia observed in 

 Japan during the years 1899 to 1903, and in those of Bloch" and Blegvad^^ 

 which, combined, represented observations on 211 cases of xerophthalmia 

 and 453 cases of keratomalacia observed from 1909 to 1920 in Denmark. 

 Mori noted a high incidence in late winter (when vitamin A storage and 

 intake are lowest) and again in association with summer diarrhea (interfer- 

 ing with absorption and utilization of vitamin A). Although he related the 

 symptoms to lack of fats in the diet, he recognized that cod liver oil was 

 much more effective therapeutically than vegetable oils. The Danish clini- 

 cians related the ocular disorders to restricted diets composed chiefly of 

 skimmed milk and gruels, and the widespread exportation of butter during 

 World War I with replacement by vegetable margerines. The discovery of 

 vitamin A as a dietary essential at this same period, and the demonstration 

 that similar eye lesions occur in laboratory animals deficient in this vitamin, 



8 P. Bitot, Gazz. med. Paris 18, 435 (1863). 

 'S. Snell, Lancet I, 8 (1876). 



8 T. Leber, Albrecht von Graefe's Arch. Ophthalmol. 29, (3), 225 (1883). 



9 H. de Gouvea, Albrecht von Graefe's Arch. Ophthalmol. 29, (1), 167 (1883). 

 '"M. Mori, Jahrb. Kinderheilk. 59, 175 (1904). 



»' C. E. Bloch, /. Hy(]. 19, 283 (1921); Am. J. Diseases Children 27, 139 (1924); 28, 



659 (1924). 

 12 O. Blegvad, Am. J. Ophthalmol. 7, 89 (1924). 



