OCULAR IRRITATION - MICROSCOPIC CHANGES OCCURRING OVER TIME IN THE RAT WITH SURFACTANTS OF KNOWN IRRITANCY

The pathology of surfactant-induced ocular irritation, especially in t he context of accidental human exposures and animal tests used to asse ss a surfactant's potential ocular irritation, is not well understood. The purpose of this study was to characterize the microscopic changes in rats at 3 hr and on days 1, 2, 3, 4, 7, 14, and 35 following treat ment with anionic, cationic, and nonionic surfactants of differing irr itancy. The right eye of each rat was treated by placing 10 mu l of a surfactant directly on the cornea. Untreated left eyes served as the c ontrols. At each time point, eyes and eyelids were macroscopically exa mined and collected for microscopic examination. Macroscopically, the differing levels of irritation were characterized by differences in in cidence and magnitude of scores, reflecting involvement of the cornea, conjunctiva, and iris, as well as by the incidence of neovascularizat ion and time to recovery. Microscopically, differences in the area and depth of injury paralleled the differences seen grossly and the relat ive irritancies of the various surfactants. All surfactants affected t he corneal and conjunctival epithelium. All surfactants, except the sl ightly irritating anionic surfactant, caused corneal stromal changes, with this involvement being proportional to their overall level of irr itation. Corneal endothelial cell effects principally occurred with on ly the severely irritating cationic surfactant. Over time, responses t o surfactants of differing irritancy were qualitatively and quantitati vely different, and these differences correlated with the extent of in itial injury. Qualitative differences in response included presence of keratocyte regeneration, corneal neovascularization, and conjunctival ization of the corneal epithelium with all of the surfactants except t he slight irritant. Quantitative differences in response occurred in t he extent of epithelial regeneration, edema, and inflammation for surf actants of slight to severe irritancy, and with neovascularization, ke ratocyte regeneration, and conjunctivalization for surfactants of mild to severe irritancy. These results suggest that by defining initial a rea and depth of injury associated with an ocular irritant, it may be possible to predict the subsequent response and final outcome. Such an approach would be applicable to the development of mechanistically ba sed in vitro assays.