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

Tschopp, Markus MD; Stary, Johannes; Frueh, Beatrice E MD; Thormann, Wolfgang PhD; De Smet, Julie; Van Bocxlaer, Jan PhD; Tappeiner, Christoph MD

doi: 10.1097/ICO.0B013E31823E29D5
Clinical Science

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 μg/mL) and voriconazole (52.70 ± 8.76 μg/mL) was significantly lower than in the untreated control group (ofloxacin: 18.51 ± 6.08 μg/mL, P = 0.005; voriconazole: 62.43 ± 13.5 μg/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.

From the *Department of Ophthalmology, Inselspital, University Hospital of Bern, Bern, Switzerland; †Department of Clinical Pharmacology and Visceral Research, University of Bern, Bern, Switzerland; and ‡Laboratory of Medical Biochemistry and Clinical Analysis, University of Ghent, Ghent, Belgium.

Received for publication August 5, 2011; revision received September 25, 2011; accepted October 14, 2011.

The authors state that they have no financial or conflicts of interest to disclose.

Reprints: Beatrice E. Frueh, Department of Ophthalmology, Inselspital, University Hospital of Bern, 3010 Bern, Switzerland (e-mail:

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.