Corneal Penetration of Polyhexamethylene Biguanide and Chlorhexidine Digluconate

Objective: Cationic antiseptics, such as polyhexamethylene biguanide (PHMB) and chlorhexidine digluconate (CHG), are widely used for the topical treatment of Acanthamoeba keratitis. The aim of this study was to investigate the corneal penetration of PHMB and CHG topically administered as eye drops and to study the effect of PHMB and CHG on the epithelial barrier function.
Methods: The penetration was evaluated in vitro in rabbit corneas clamped in artificial perfusion chambers. Two different preparations of PHMB 0.02% (Cosmocil and Lavasept) and CHG 0.02% eye drops were administered twice each hour for up to 8 hours to the rabbit corneas with and without epithelium. The amount of drug penetrating into the anterior chamber was measured using capillary electrophoresis with contactless conductivity detection. The integrity of the epithelial barrier function was evaluated by adding fluorescein to the PHMB or CHG eye drops. The fluorescence of the anterior chamber perfusate was measured continuously throughout the experiment. Corneas treated with fluorescein alone (in either NaCl 0.9% or benzalkoniumchloride (BAC) eye drops) served as controls.
Results: Neither PHMB nor CHG were detectable at any time in the anterior chamber perfusate of either the corneas with or without epithelium. PHMB and CHG treatment resulted in a minimal increase of fluorescein penetration as compared to the controls treated with 0.9% NaCl/0.05% fluorescein eye drops indicating a slight disruption of the epithelial barrier function caused by the biguanides. In contrast fluorescein penetration was much further enhanced when BAC 0.01% control eye drops were administered.
Conclusion: This study showed that neither PHMB nor CHG readily penetrated through the cornea to the anterior chamber, which may explain why treatment of Acanthamoeba keratitis requires many months of sustained topical drug administration. PHMB and CHG had little effect on the epithelial barrier function compared to BAC, which is widely used as a preservative in eye drops.