Anin vitroAnalysis of Aminoglycoside Corneal Epithelial Toxicity

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Abstract
We evaluated the cytotoxicity of four aminoglycoside agents (neomycin, gentamicin, tobramycin, and amikacin) using an in vitro confluent rabbir corneal epithelial cell culture model. Primary corneal epithelial cell culturs were established and cells replated at 2 × 104 cells/2 cm2 well. After 48 hours either vehicle or an antibiotic was added at varying concentrations, each for 5, 30, or 60 minutes. H-thymidine was added immediately after drug removal and incorporation was measured 8 hours after drug or vehicle exposure. Comparisons of each drug to vehicle were expressed as % inhibition of control culture values. At the 5-minute exposure time tobramycin and amikacin showed no significant inhitition at any concentration, whereas neomycin and gentamicin showed significant inhibition at 6 mg/ml and 3.5 mg/ml or greater concentrations, respectively (p< 0.05). At 30- and 60-minute exposure times all agents demonstrated significant inhibition at all tested concentrations in a non-dose dependent fashion (p<0.05). These in vitro data corroborate the animal and limited clinical data available for the aminoglycosides. Based on these toxicity profiles, tobramycin appears to be the topical agent of choice in the treatment of susceptible bacterial keratitis.