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N L Burstein; Preservative alteration of corneal permeability in humans and rabbits.. Invest. Ophthalmol. Vis. Sci. 1984;25(12):1453-1457.
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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.
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