title: A study of stromal riboflavin absorption in ex vivo porcine corneas using new and existing delivery protocols for corneal cross-linking.
abstract: OBJECTIVE
  To indirectly measure stromal riboflavin penetration using commercially available riboflavin solutions and new and existing epithelium-off, trans-epithelial and iontophoresis-assisted delivery protocols.
  
  
  METHODS
  Forty porcine eyes were divided into eight groups. Group 1: Ricrolin applied to the de-epithelialised cornea for 30 min; Group 2: epithelium-intact, no treatment; Groups 3-5: epithelium-intact, 30-min application of Ricrolin TE, Mediocross TE or ParaCel/Vibex, respectively. Group 6: epithelium-intact, Ricrolin(+) iontophoresis-assisted delivery for 5 min; Group 7: epithelium-intact, Ricrolin(+) iontophoresis-assisted delivery for 5 min with a 20-min riboflavin soak; and Group 8: epithelium-intact, Ricrolin(+) iontophoresis-assisted delivery for 5 min, 15-min soak and another 5 min of iontophoresis. After a saline wash, light transmission spectra were obtained from each cornea, before and after epithelial removal.
  
  
  RESULTS
  Corneas in groups 1 and 8 showed a distinct riboflavin absorption peak between 400 and 520 nm. The optical density of the corneas in groups 3-7 did not differ significantly from that of the untreated corneas (group 2).
  
  
  CONCLUSIONS
  A modification to the standard iontophoresis trans-epithelial technique resulted in successful penetration of riboflavin into the stroma and appears to offer the most promise for epithelium-on cross-linking.
authors.affiliation: School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Hayes
authors.affiliation: School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors.forename: Siân R
authors.initials: SR
authors.lastname: Morgan
authors.affiliation: Department of Ophthalmology, St. Thomas' Hospital, London, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: O'Brart
authors.affiliation: School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: O'Brart
authors.affiliation: School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Meek
mesh_terms: D000818:Animals; D003319:Corneal Stroma / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003646:Debridement; D016503:Drug Delivery Systems; D019573:Epithelium, Corneal / Q000502:physiology; D007478:Iontophoresis; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D012256:Riboflavin / Q000493:pharmacokinetics*; D013552:Swine; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D012256:Riboflavin
keywords: cornea; cross-linking; iontophoresis; spectrophotometry