Impact of Corneal Cross-linking on Drug Penetration in an Ex Vivo Porcine Eye Model

Purpose: To analyze the influence of corneal cross-linking (CXL) using ultraviolet-A and riboflavin on corneal drug penetration of topically applied drugs. Methods: In an ex vivo porcine eye model, eyes were randomly assigned to CXL or control treatment. Central corneal thickness and anterior chamber depth were measured with a Pentacam device. In the CXL group, eyes were treated with CXL using ultraviolet-A (370 nm) and riboflavin, whereas in the control group only riboflavin was applied without irradiation. Subsequently, 0.3% ofloxacin (n = 40 eyes) or 1% voriconazole (n = 40 eyes) eye drops were applied to the cornea every 5 minutes for 30 minutes. Aqueous humour samples were obtained performing an anterior chamber tap. The concentrations of ofloxacin and voriconazole were determined with high-pressure liquid chromatography. Groups were compared performing a Mann-Whitney test. Results: In the CXL group, the mean concentration of ofloxacin (13.33 +/- 4.67 mu g/mL) and voriconazole (52.70 +/- 8.76 mu g/mL) was significantly lower than in the untreated control group (ofloxacin: 18.51 +/- 6.08 mu g/mL, P = 0.005; voriconazole: 62.43 +/- 13.5 mu g/mL, P = 0.01). This corresponds to a reduction in permeability of 27.98% for ofloxacin and 15.59% for voriconazole. Central corneal thickness and anterior chamber depth were comparable in the CXL and control groups (P. 0.05, each). Conclusions: CXL reduces the corneal permeability of ofloxacin and voriconazole. This may be of clinical significance, for example, in keratitis treatment.