Impact of corneal cross-linking on drug penetration in an ex vivo porcine eye model.
OBJECTIVE
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.
Department of Ophthalmology, Inselspital, University Hospital of Bern, Bern, Switzerland.
Markus
M
Tschopp
Johannes
J
Stary
Beatrice E
BE
Frueh
Wolfgang
W
Thormann
Julie
J
De Smet
Jan
J
Van Bocxlaer
Christoph
C
Tappeiner
D000287:Administration, Topical; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D023421:Models, Animal; D015242:Ofloxacin / Q000493:pharmacokinetics; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011743:Pyrimidines / Q000493:pharmacokinetics; D011897:Random Allocation; D012256:Riboflavin / Q000494:pharmacology*; D013552:Swine; D014230:Triazoles / Q000493:pharmacokinetics; D014466:Ultraviolet Rays; D065819:Voriconazole
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D017319:Photosensitizing Agents; D011743:Pyrimidines; D014230:Triazoles; D015242:Ofloxacin; D065819:Voriconazole; D012256:Riboflavin