When animals are restricted to a diet lacking in fat-soluble A, there develops after a few weeks a peculiar pathological condition of the eyes which is so characteristic that it must be regarded as one of the manifestations of a specific syndrome. It has not yet received from pathologists the attention it deserves. In 1909 Knapp (13) restricted rats to a diet of isolated and purified food substances, consisting of proteins, carbohydrates, fats and mineral salts, and described a severe conjunctivitis which developed as the nutrition of his animals failed. In other experiments lecithin, cholesterol and nucleic acid were added to the basal diet, and although the animals suffered from malnutrition and died, the characteristic eye symptoms did not appear. This is probably to be explained by the presence of fat-soluble A as an impurity in the lipins which he employed as additions to the experimental diet.

Freise, Goldschmidt and Frank (14), in 1913 observed the same eye disorder in their experiments with rats which they restricted to a diet similar to that used by Knapp. They described the condition in more detail than did Knapp. They stated that in about three weeks from the beginning of the experiment the eyelashes of the animals began to fall out. There was also a retraction of the eyeballs from spasm of the extrinsic muscles of the eyes. In five to six weeks the sclerotic coat became dry, the cornea clouded and finally ulcerous, but without marked inflammation. The fur of the animals became rough. They succumbed to malnutrition, and histological examination of the sclerotic coat revealed the typical picture of keratomalacia as it is seen in man. In cases where the ulceration of the sclera of one eye was well developed, and was beginning to show in the other, the process could be entirely arrested by the administration, suggested by the work of Hopkins, of two cubic centimeters of skim milk per day. These workers believed that the condition developed only in young growing animals, and that it was closely related to the phenomena of growth. They attributed the condition to lack of "accessory" substances in the diet.