VIII. VITAMIN A DEFICIENCY IN HUMAN BEINGS 145 



ship to the pathologic (.•luuiges but probably represent orguiiisms normuUy 

 present in the conjunctival sac which thrive in greater numbers in the 

 debris of sloughed epitlielial cells. 



Kruse'^^ has described the widespread occurrence of Hat or slightly raised, 

 whitish to yellow conjunctival spots, as seen under biomicroscopic examina- 

 tion of the eye. Unlike Bitot's spots, these result from cellular infiltration 

 and other alterations in the subepithelial tissues. Kruse thinks that they 

 may reflect a prolonged but mild insufficiency of vitamin A. The validity 

 of these interpretations has been challenged by others, especially Berliner,^*" 

 who regards these spots as Pingueculae, although Kruse'*"" has ably de- 

 fended his beliefs. The varied evidence on this question, recently summa- 

 rized by Stern,^ is still insufficient to permit a satisfactory conclusion as to 

 the diagnostic value of these conjunctival changes. 



3. HiSTOPATHOLOGY 



Descriptions of the histopathologic changes characterizing xerophthal- 

 mia and keratomalacia in man are meager. Fatal outcome is rare and 

 occurs usually in infants as a result of associated pneumonic disease. 

 Permission for removal of orbital structures at necropsy is not easy to 

 obtain. Since ophthalmic examination provides much information concern- 

 ing the superficial changes, and since much attention has been given to 

 the histopathology in experimental animals, there has been only limited 

 exploration of the pathologic changes in man. 



As early as 1883, Leber** described a thickening and hyperplasia of the 

 bulbar conjunctiva, with marked flattening and cornification of the super- 

 ficial cells; a similar change was also noted in the mucosa of the renal 

 pelvis. Little has been added since that time except for the studies of 

 Kreiker^^ and Sweet and K'ang,-'' based on material obtained by biopsy 

 and at necropsy. Their studies indicate that the earliest morphologic change 

 is a disappearance of goblet mucous cells from the epithelium of the bulbar 

 conjunctiva and cornea, followed by hyaline-like changes in the superficial 

 cells (stage of prexerosis). These are soon undermined and lifted off by 

 flattened, keratohyalin-laden cells of the deeper layers which progressively 

 cornify. Eventually there is formed a somewhat hyperplastic, keratinized 

 stratified epithelium resembling that of the epidermis (stage of xerosis con- 

 junctiva). In dark-skinned races considerable melanin pigment accumu- 

 lates in the basal cells of the conjunctival epithelium,^®* ^^ which is respon- 



18 H. D. Kruse, Milbank Mem. Fund Quart. 19, 207 (1941). 



>8aM. L. Berliner, Am. J. Ophthnhnol. 50, 302 (1942). 



»8b 11. D. Kruse, .4m. J. Ophthalmol. 50, 1.3S6 (1942). 



'9 A. Kreiker, Albrecht von Graefe's Arch. Ophthalmol. 124, 190 (1930). 



20 L. K. Sweet and H. J. K'ang, Am. J. Disca.^cs Children 50, 699 (1935). 



" A. Pillat, Arch. Ophthalmol. (Chicago) 9, 25 (1933). 



