Comparison of the conjunctival toxicity of topical ocular antiallergic agents.

Purpose: The aim of this study was to investigate the cytotoxic effect of topical ocular allergic agents with H1-receptor antagonism and inhibition of histamine release from mast cells on the cultured conjunctival cells of rabbit in vitro.

Methods: Cell damage by the topical ocular antiallergic agents (azelastine hydrochloride, ketotifen fumarate, and olopatadine hydrochloride) was determined by using the lactate dehydrogenase (LDH) leakage assay with the rate of dilution of 10, 20, and 30%, respectively, for a period of 0 and 30 min and 4, 12, and 24 h, and compared with the balanced salt solution-treated group. The osmolarity, pH, composition of electrolytes, preservatives, and morphologic findings of all the antiallergic agents were also evaluated.

Results: The LDH titers increased after all the antiallergic agents were exposed up to 4 h, maintained its level for 12 h, and then decreased until 24 h. There was no statistical significance among the three agents. The greater titer of LDH, the more conjunctival cells became swollen or round. Azelastine and ketotifen showed greater LDH titer, edema, and cytoplasmic and nuclear degenerations of the conjunctival cells than that of olopatadine. The levels of Na(+), Cl(-), and pH were significantly lower with azelastine and ketotifen, compared with olopatadine, and all antiallergic agents contained the same concentration of benzalconium chloride.

Conclusions: When antiallergic agents are used to treat allergic conjunctivitis other than olopatadine, a particularly toxic effect on conjunctival cells associated with azelastine and ketotifen, rather than olopatadine, should be considered clinically.