Preservative alteration of corneal permeability in humans and rabbits

Isotonic, neutral buffered solutions of benzalkonium chloride or chlorhexidine digluconate were applied topically to one eye of rabbits or human subjects. Contralateral control eyes received phosphate buffered saline as placebo. One-half hour later, the tear film of both eyes was loaded with nonpreserved sodium fluorescein. Anterior chamber fluorescence levels were measured at 1 hr intervals to determine corneal permeability changes attributable to preservative action. In rabbits, corneal permeability increased with rising preservative concentration. Benzalkonium chloride 0.01% increased anterior chamber fluorescence level 1.8 (+/- 0.2 SEM) times over control eyes, while chlorhexidine digluconate 0.01% caused 1.5 (+/- 0.2 SEM) to one ratio of fluorescence in treated/untreated eyes. In human subjects, neither preservative produced significant permeability change at 0.01% concentration. However, benzalkonium chloride 0.02% caused 1.23 (+/- 0.08 SEM) permeability increase. The results support the hypothesis that rabbits are more sensitive to single-dose applications of preservatives than humans.