Pharmacological modification of the epithelial permeability by benzalkonium chloride in UVA/Riboflavin corneal collagen cross-linking.
OBJECTIVE
To examine the biomechanical effect and the UVA-absorption of a riboflavin/UVA cross-linking method, which suggests leaving the epithelium intact and applying benzalkonium chloride (BAC) on rabbits' corneas.


METHODS
In total, 32 eyes from 16 rabbits were divided into 4 groups. Group 1 was treated with intact epithelium and without BAC. In groups 2 and 3, the epithelium was left intact and a hypoosmolar solution of riboflavin that contained BAC 0.02% or 0.04% was used. Group 4 was treated according to the standard protocol with mechanical debridement of the epithelium. After the treatment of both eyes, the rabbits were euthanized to prepare the corneas in order for the determination of the riboflavin absorption coefficient and biomechanical properties.


RESULTS
The absorption coefficients of groups 2, 3, and 4 were significantly increased compared to group 1. There were no significant differences between groups 2, 3, and 4. Stress-strain values and Young's modulus for groups 2, 3, and 4 were significantly increased compared to group 1. The stiffening effects did not differ within groups 2, 3, and 4. The resistance to enzymatic digestion was significantly increased in groups 2, 3, and 4 as compared to group 1.


CONCLUSIONS
Treatment with BAC 0.02% induces sufficient epithelial permeability for the passage of riboflavin, which enables its stromal diffusion and results in increased corneal stiffening after cross-linking as compared to the standard protocol. Further safety studies will be required before clinical use.
Kissner
Anja
A
Department of Ophthalmology, Carl Gustav Carus University Hospital, Dresden, Germany. anja.kissner@uniklinikumdresden.de
Spoerl
Eberhard
E
Jung
Roland
R
Spekl
Kathrin
K
Pillunat
Lutz E
LE
Raiskup
Frederik
F
D000042:Absorption; D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism*; D003319:Corneal Stroma / Q000187:drug effects / Q000378:metabolism; D003432:Cross-Linking Reagents; D003646:Debridement; D004847:Epithelial Cells / Q000378:metabolism; D019573:Epithelium, Corneal / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011817:Rabbits; D012256:Riboflavin / Q000493:pharmacokinetics*; D014466:Ultraviolet Rays
D001548:Benzalkonium Compounds; D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D011310:Preservatives, Pharmaceutical; D003094:Collagen; D012256:Riboflavin