title: Riboflavin osmolar modification for transepithelial corneal cross-linking.
abstract: OBJECTIVE
  To investigate the influence of osmolarity on the transepithelial permeability of riboflavin solutions in a cross-linking procedure.
  
  
  METHODS
  Several riboflavin 0.1% solutions that contained different NaCl and benzalkonium chloride (BAC) concentrations were applied to 36 rabbit eyes for 30 min. To serve as a control, the epithelium was removed in group A (standard protocol). The groups then received the following solutions: (A) riboflavin 0.1% in NaCl 0.9% solution; (B) riboflavin 0.1% in NaCl 0.44% solution with BAC 0.02%; (C) riboflavin 0.1% in NaCl 0.44% solution with BAC 0.01%; (D) riboflavin 0.1% in NaCl 0.44% solution without BAC; (E) riboflavin 0.1% in NaCl 0.9% solution with BAC 0.02%; and (F) riboflavin 0.1% in NaCl 0.9% solution without BAC. Six eyes in each group were treated. The absorption coefficients of the corneas were measured to characterize the riboflavin penetration into the cornea.
  
  
  RESULTS
  There is a large difference in the transepithelial riboflavin penetration of riboflavin 0.1% + BAC 0.02% solutions that contain different NaCl concentrations (NaCl 0.9% versus NaCl 0.44%). The absorption coefficients differed by more than a factor of two (P = 0.004). No statistically significant difference was found between riboflavin 0.1% in NaCl 0.44% solution containing BAC 0.02% and BAC 0.01%. Compared to the standard protocol, these solutions resulted in an absorption coefficient of 37% (BAC 0.02%) and 33% (BAC 0.01%) of the standard epithelium-off procedure.
  
  
  CONCLUSIONS
  The transepithelial riboflavin solution should contain no dextran, but it should include 0.01% BAC and 0.44% NaCl to promote the permeability of riboflavin through the epithelium, resulting in a sufficient concentration of riboflavin in the corneal stroma.
authors.affiliation: Department of Ophthalmology, Carl Gustav Carus University Hospital, Fetscherstrasse 74, Dresden, Germany. frederik.raiskup@uniklinikum-dresden.de
authors.forename: Frederik
authors.initials: F
authors.lastname: Raiskup
authors.forename: Roberto
authors.initials: R
authors.lastname: Pinelli
authors.forename: Eberhard
authors.initials: E
authors.lastname: Spoerl
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000493:pharmacokinetics; D001682:Biological Availability; D001692:Biological Transport; D003319:Corneal Stroma / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000493:pharmacokinetics*; D004338:Drug Combinations; D019573:Epithelium, Corneal / Q000378:metabolism*; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics; D009994:Osmolar Concentration; D010539:Permeability; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011817:Rabbits; D012256:Riboflavin / Q000493:pharmacokinetics*; D012965:Sodium Chloride / Q000493:pharmacokinetics; D014466:Ultraviolet Rays
chemical_list: D001548:Benzalkonium Compounds; D003432:Cross-Linking Reagents; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D017319:Photosensitizing Agents; D012965:Sodium Chloride; D012256:Riboflavin