Corneal epithelial testing strategies for safety evaluation of ophthalmic formulations.

The toxicity of an ophthalmic formulation was tested both in vivo and in vitro. Initial tests on transformed human corneal epithelial (HCE-T) cells in monolayer cultures resulted in adverse effects on cell morphology. The adverse effects were unexpected since the formulation caused no damage to the cornea in vivo. These results suggested HCE-T monolayers do not adequately model the intact corneal epithelium. Therefore, further in vitro studies were conducted to investigate reversibility of morphologic changes, proliferation, cell viability, and effects on corneal epithelial barrier function. These tests showed that the formulation had no adverse effects on cell viability and proliferation. Multilayered cultures of HCE-T cells at an air interface provide a morphologic and physiologic model more relevant to the in vivo cornea. This study demonstrates the importance of selecting appropriate models when conducting in vitro toxicity studies so that potentially effective ophthalmic formulations are not rejected based on false positive in vitro endpoints.