HISTOPATHOLOGICAL EFFECTS OF TOPICAL OPHTHALMIC PRESERVATIVES ON RAT CORNEOCONJUNCTIVAL SURFACE

Purpose. Long term use of topical drugs has clearly been shown to indu ce toxic immunopathological changes in the ocular surface. However, li ttle is known concerning the respective roles of active compounds and preservatives. Benzalkonium chloride (BAG) is the most used preservati ve and its cytotoxicity is well known, but other preservatives have no t yet been clearly evaluated. We thus performed a comparative study to investigate toxic side effects induced in the rat ocular surface by a pplications of various preservatives, with special attention to inflam matory infiltrates. Methods. A total of 35 brown Norway rats were divi ded into seven groups of five each. They received, for one month, in b oth eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chlori de, 0.01% benzododecinium bromide, 0.004% thiomersal, 0.05% methyl par ahydroxybenzoate or phosphate-buffered saline (PBS), the last group re maining untreated. Then, animals were sacrificed and eyes were process ed for histological and immunological procedures with monoclonal antib odies to rat immunocompetent cells. Results. When compared to controls , all preservative-treated eyes consistently showed corneal and conjun ctival damage, including epithelial alterations, various degrees of ke ratinization and inflammatory infiltrates at the limbus and within the conjunctival stroma and epithelium. No difference was found between t he five tested drugs. Conclusions. This study confirms that most prese rvatives used in ophthalmic eyedrops may similarly induce strong histo pathological and inflammatory changes in the ocular surface after shor t term use. Although obtained in animal model, these results confirm s trong toxic side effects in patients with preexisting ocular surface d isorders and/or receiving topical drugs for long periods.