title: Pharmacological modification of the epithelial permeability by benzalkonium chloride in UVA/Riboflavin corneal collagen cross-linking.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Carl Gustav Carus University Hospital, Dresden, Germany. anja.kissner@uniklinikumdresden.de
authors.forename: Anja
authors.initials: A
authors.lastname: Kissner
authors.forename: Eberhard
authors.initials: E
authors.lastname: Spoerl
authors.forename: Roland
authors.initials: R
authors.lastname: Jung
authors.forename: Kathrin
authors.initials: K
authors.lastname: Spekl
authors.forename: Lutz E
authors.initials: LE
authors.lastname: Pillunat
authors.forename: Frederik
authors.initials: F
authors.lastname: Raiskup
mesh_terms: 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
chemical_list: D001548:Benzalkonium Compounds; D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D011310:Preservatives, Pharmaceutical; D003094:Collagen; D012256:Riboflavin